Datasets:

qualis2006

/

PUBMED_title_abstracts_2020_baseline

like 1

WDR35 variants in a cranioectodermal dysplasia patient with early onset end-stage renal disease and retinal dystrophy. Cranioectodermal dysplasia (CED) is rare heterogeneous condition. It belongs to a group of disorders defined as ciliopathies and is associated with defective cilia function and structure. To date six genes have been associated with CED. Here we describe a 4-year-old male CED patient whose features include dolichocephaly, multi-suture craniosynostosis, epicanthus, frontal bossing, narrow thorax, limb shortening, and brachydactyly. The patient presented early-onset chronic kidney disease and was transplanted at the age of 2 years and 5 months. At the age of 3.5 years a retinal degeneration was diagnosed. Targeted sequencing by NGS revealed the presence of compound heterozygous variants in the WDR35 gene. The variants are a novel missense change in exon 9 p.(Gly303Arg) and a previously described nonsense variant in exon 18 p.(Leu641*). Our findings suggest that patients with WDR35 defects may be at risk to develop early-onset retinal degeneration. Therefore, CED patients with pathogenic variation in this gene should be assessed at least once by the ophthalmologist before the age of 4 years to detect early signs of retinal degeneration.

Formation of carotenoid supramolecular aggregates in nanocarriers monitored via aggregation-sensitive chiroptical output of enantiopure (3S,3'S)-astaxanthin. The aggregation-sensitive chiroptical (ECD and RROA) output, provided by enantiopure (3S,3'S)-astaxanthin, was used to investigate and control the assembling processes of the carotenoid in Pluronic F-127 nanoparticles. The process of carotenoid J-aggregation inside nanocarriers is interfered with by the formation of kinetically stabilized H1 self-assemblies outside the micelles. Nanocarriers with encapsulated stable J-aggregates provide controlled release of carotenoid molecules to primary murine adipocytes.

A propensity score-matched comparison of patient satisfaction following periacetabular osteotomy or total hip arthroplasty for developmental dysplasia of the hip in an Asian cohort. No studies have compared patient satisfaction between periacetabular osteotomy (PAO) and total hip arthroplasty (THA) for osteoarthritis (OA) secondary to developmental dysplasia of the hip (DDH) in Asian cohorts. Multivariate analyses were applied to determine whether patient demographics and postoperative patient-reported outcomes were correlated with postoperative patient satisfaction in 737 DDH patients (251 PAO and 486 THA patients). Additionally, postoperative patient satisfaction, Oxford Hip Score (OHS), University of California-Los Angeles (UCLA) activity score, and sports participation were compared between propensity-matched PAO and THA patients for OA secondary to DDH (Kellgren-Lawrence grade II: 32 PAO and 16 THA patients, grade III: 20 PAO and 40 THA patients). Of the 737 patients, 663 patients (90%) were postoperatively satisfied. Multivariate analysis demonstrated that THA was positively correlated with patient satisfaction. Furthermore, high postoperative OHS-pain, OHS-ADL, and UCLA scores were positively correlated with satisfaction. In propensity-matched PAO and THA patients, PAO elicited greater patient satisfaction than THA for KL grade II OA secondary to DDH, with comparable postoperative OHS (including the pain and ADL subscale), UCLA score, and sports participation rate. In contrast, THA resulted in better satisfaction and OHS-pain for KL grade III OA secondary to DDH, with comparable postoperative OHS-ADL, UCLA score, and sports participation rate in the 2 surgeries. Both PAO and THA procedures offer distinct patient satisfaction advantages based on preoperative OA severity. These findings can assist in the clinical decision-making process for the surgical treatment of middle-aged patients with symptomatic DDH.

Only as a last resort: Sociocultural differences between women and men explain women's heightened reaction to threat, not evolutionary principles. The target article proposed that women display greater self-protectiveness than men to major physical and social threats because such self-protective responses have higher fitness value for women than men. Rather than having evolutionary roots, we suggest the various physiological, behavioral, and emotional responses to social and physical threats exhibited more by women than men are instead rooted in sociocultural forces.

Identification, biogenesis, and function prediction of a novel circRNA_3238 of chicken. With the development of high-throughput sequencing, circular RNA has come into people's vision and attracted more and more attention. Many studies have found that circular RNA plays an important role in a variety of biological processes and the occurrence and development of diseases. According to the previous sequencing results, circRNA_3238 was differentially expressed in ALV-J infected group and the non-infected group was selected for subsequent verification and analysis. We found that circRNA_3238 is a stable, circular transcript, which mainly exists in the cytoplasm. And it is widely expressed in various tissues of chickens, and highly expressed in lung, lymph, and bursa of fabricius. Bioinformatics results show that circRNA_3238 and the predicted target genes enriched MAPK signaling pathway, Notch signaling pathway, and other pathways related to disease or immune, revealing circRNA_3238 may indirectly regulate the process of ALV-J infection by regulating target genes.

Staying alive includes adaptations for catalyzing cooperation. The target article interprets women's lower competitiveness than men's as evidence of adaptation to help women avoid physical conflicts and stay alive. This commentary advances the additional hypothesis that strategically suppressing competitiveness, thus signaling egalitarian intentions, could be an adaptation to catalyze cooperative behavior from males and females, turning natural competitors (other women) into allies and men into supportive partners.

Sustainable approach for biodiesel production and wastewater treatment by cultivating Pleusrastrum insigne in wastewater. The globalized modern world has been confronted with some of the most challenging problems, most of which arise from human activities. Overexploitation of fossil fuels which leads to energy and environmental crisis, and loss of aquatic ecosystem due to improper disposal of household and industrial waste into water bodies constitute some of the biggest emerging global problems. In this study, an unconventional and sustainable approach to produce biodiesel was analyzed by growing Pleurastrum insigne in different wastewater. The growth of P. insigne in wastewater in turn resulted in up to 93.61% reduction in biological oxygen demand, 58.62% reduction in total phosphorus content, and up to 76.61% total nitrogen removal in the wastewater. The total lipid content of the organism was highest in wastewater sample 6 (30.47%). The fatty acid profile also showed a high percentage of C16 and C18 fatty acids which are desirable fatty acids for a high-grade fuel. Production of biodiesel conforming to international standards was predicted from P. insigne cultivated in wastewater confirming the effectiveness of combining wastewater treatment and biodiesel production. Novelty statement: Pleurastrum insigne has never been studied before for phytoremediation of wastewater and biodiesel production. This novel research highlighted the application of P. insigne in wastewater treatment and the viable scope in biodiesel production. This work aimed to provide a significant contribution in reducing the cost of production of biodiesel from microalgae while shedding new light on an eco-friendly approach to wastewater treatment.

Psychological and behavioral implications of self-protection and self-enhancement. Self-protection can have psychological and behavioral implications. We contrast them with the implications of a self-enhancement strategy. Both self-enhancement and self-protection have costs and benefits as survival strategies, and we identify some of the emotional, cognitive, and behavioral tradeoffs associated with the differential preferences for each strategy. New analyses on a large existing data set confirm the target article's hypothesis that women are more attuned than men to potential negative consequences of innovations.

Women need to stay alive and protect reproductive choice. Defense of reproductive choice is an important motivation in women's self-protection psychology for which the "staying alive theory" cannot fully account. Evidence indicates that some elements of women's self-protection psychology function to protect reproductive choice rather than survival, or may be equally well explained by either motivation. Integrating perspectives will result in greater explanatory breadth and precision in theory testing.

Biological sex, by-products, and other continuous variables. Sex/gender is a continuous variable that researchers frequently treat as dichotomous. This practice can mask continuous underlying adaptive traits and yield spurious dichotomous "sex differences." As such, many sex differences in self-protection may be evolutionary by-products of underlying adaptations rather than adaptations themselves. Binary analysis of continuous sex/gender is ill-considered science that can contribute to inequality and counterproductive public policy.

A comparison assessment of landfill waste incineration and methane capture in the central region of Mexico. This article aims to conduct a techno-economic feasibility assessment of producing energy by waste incineration and methane capture in the central region of Mexico. Three scenarios at different efficiency rates were considered: 50, 80 and 100%. For the methane project, yields and power capacity were determined using the potential generation rate and the degradable organic carbon content through the LandGEM model. For incineration, the waste calorific potential and the average moisture content were used to estimate the achievable electrical performance. The estimated annual energy was 35,018 GWh for methane, compared to 537.71 GWh for incineration. Both projects reported financial economic feasibilities when evaluated at a discount rate of 12%. Incineration reported an net present value of US$49,942,534 and an internal rate of return of 26% in contrast to US$4,054,109 and 17% for the methane project. Although the payback period for incineration was lower than for methane, its levelized cost of energy was significantly higher. These results are intended to assist the decision-making process when planning and developing waste management strategies under principles of circular economy in Mexico and similar regions worldwide.

Pathological complexity and the evolution of sex differences. Benenson et al. provide a compelling case for treating greater investment into self-protection among females as an adaptive strategy. Here, we wish to expand their proposed adaptive explanation by placing it squarely in modern state-based and behavioural life-history theory, drawing on Veit's pathological complexity framework. This allows us to make sense of alternative "lifestyle" strategies, rather than pathologizing them.

Toward a more domain-specific conceptualization of female traits: A commentary on Benenson et al. (2022). Benenson et al. (2022) amass impressive evidence of robust sex differences as support for expanding "staying alive" theory. We argue for a broader and more domain-specific conceptualization focusing on life history tradeoffs between survival and mating success. Using three examples - women's disgust, fear of rape, and cultivation of bodyguards - we illustrate these tradeoffs and suggest a broader theoretical framework.

An expanded "staying alive" theory (SAT) underplays complexity in Homo sapiens. The target article takes myriad human female patterns and aligns them as a unit emerging from an expanded version of "staying alive" theory (SAT). Females and males do differ, however, to treat the complexity of human response to threats as an explicit, evolved sexually dimorphic package is not reflective of current knowledge regarding health, sex/gender, and behavior in Homo sapiens.

"Staying alive" in the context of intimate partner abuse. Females are disproportionately affected by intimate partner abuse that can result in severe physical and mental harm. Benenson et al. provide little exploration of how female-evolved traits enhance females' survival in abusive relationships. Discussion centres on "why" females do not "just leave" an abusive relationship and the effectiveness of female-evolved traits in navigating intimate partner abuse over time.

Women amid the COVID-19 pandemic: Self-protection through the behavioral immune system. Studies of the activation of the behavioral immune system triggered by the coronavirus disease-2019 pandemic have demonstrated that evolutionary explanations of individual differences in self-protection should not be based only on parental investment and sexual selection theory. An evolutionary model must also incorporate individual differences that arise within each sex as a result of life history strategies and attachment patterns.

Somatic maintenance/reproduction tradeoffs and human evolution. The authors propose that many morbidities higher in women than men are adaptations protecting survival, selected because survival has been especially crucial to mothers' reproductive success. Following their lead, I pursue variation in tradeoffs between reproduction and survival recognized by Darwin that were likely central to the evolution of many traits that distinguish us from our great ape cousins.

Female advantage in threat avoidance manifests in threat reaction but not threat detection. Threat avoidance involves both detection of a threatening stimulus and reaction to it. We demonstrate with empirically validated stimuli (that are threatening, nonthreatening-negative, neutral, or positive) that threat detection is more pronounced among males, whereas threat reactivity is more pronounced among females. Why women are less efficient detectors of threat challenges Benenson et al.'s conceptual analysis.

A review of comprehensive utilization of red mud. Red mud (RM) is a solid waste generated during the process of alumina production. RM has already posed a serious environmental threat with the development of the alumina refining industry. The comprehensive utilization of RM has attracted much attention due to its large-scale generation and harmful nature. This paper introduces the characteristics and state of RM and summarizes the relevant research on the comprehensive utilization of RM. The results show that comprehensive utilization of RM is mainly focused on the preparation of building materials, the extraction of valuable metals, catalyst synthesis and environmental protection. Besides, the article discusses the existing problems while utilizing RM. Prospects and suggestions for different utilization methods of RM are proposed.

The "staying alive" theory reinforces stereotypes and shows women's lower quality of life. Staying alive theory explains why women have more effective self-protective mechanisms in terms of woman's role as a mother and caregiver. This theory reinforces stereotypes and the relationship of oppression and submission to men. Somewhat paradoxically, it also points to women's lower quality of life, which may be explained by their greater fear of threats caused by men's power.

Sex differences in longevity are relative, not independent. I ask three questions related to the claims made within the staying alive theory (SAT): Is survival more fitness-enhancing for females than for males? Does the historical record on sex differences in mortality support the SAT? Is it possible to talk about "independent selective pressures on both male and female traits" when all we have are sex/gender comparisons?

Societies also prioritize female survival. We extend Benenson et al.'s hypothesis from the individual level to the societal level. Because women have highly limited reproductive rates, societies have generally prioritized female survival and regarded males as expendable. We describe various lines of evidence that are consistent with this hypothesis, and we offer additional predictions about differential attitudes toward male versus female endangerment.

Harm or protection? Two-sided consequences of females' susceptible responses to multiple threats. The target article presented a plausible argument that females' susceptibility to threats might be self-protection for staying alive, but some evidence requires scrutiny. We need to consider (1) the biases of narrative reviews, (2) subjective life quality, and (3) the shadow side of extreme reactions to threats before concluding that females' threat-based response is a self-protection mechanism that promotes survival.

Sex differences are insufficient evidence of ecological adaptations in human females. Benenson et al. postulate that human females evolved unique survival adaptations to facilitate maternal and grandmaternal care. This hypothesis is consistent with the broader hypothesis that female phenotypes are more ecologically optimal, but further evidence is needed to make a compelling case that sex differences in self-protection are not primarily the result of more intense sexual selection on males.

Evaluation of 11 C-choline positron emission tomography/computed tomography for determining treatment response in castration-resistant prostate cancer patients. The utility of 11 C-choline positron emission tomography/computed tomography for determining treatment response as compared with prostate-specific antigen response and prognosis prediction in castration-resistant prostate cancer patients was investigated. Eighty-four 11 C-choline-positron emission tomography/computed tomography scans before/after treatments with abiraterone (n = 12 patients), enzalutamide (n = 3), docetaxel (n = 9), cabazitaxel (n = 5), radiation therapy alone (n = 3), radiation therapy, enzalutamide, and/or abiraterone (n = 5), radium-223 (n = 4), and radiofrequency ablation (n = 1) in 42 castration-resistant prostate cancer patients were retrospectively examined. Prostate-specific antigen values were determined before and after treatment. Using the Kaplan-Meier method, the correlation of Positron Emission Tomography Response Criteria In Solid Tumors with prostate-specific antigen response and prognostic impact was evaluated. Pretreatment 11 C-choline-positron emission tomography/computed tomography findings identified local, lymph node, bone, and visceral metastasis in 12, 12, 29, and five patients, respectively. Following treatments, complete metabolic response was noted in one, partial metabolic response in eight, stable metabolic disease in 13, and progressive metabolic disease in 20. Mean prostate-specific antigen change for complete metabolic response, partial metabolic response, stable metabolic disease and progressive metabolic disease was -48.9%, -55.0% (range -92.4% to -19.1%), -4.2% (-33.2% to 35.1%), and 142.7% (30.7% to 373.8%), respectively, significantly greater in the progressive metabolic disease cases (P < 0.01). Positron Emission Tomography Response Criteria In Solid Tumors was well correlated with prostate-specific antigen change. Patients with no progression (complete metabolic response/partial metabolic response/stable metabolic disease) showed significantly longer cancer-specific survival than progressive metabolic disease (P < 0.005). Using pretreatment 11 C-choline-positron emission tomography/computed tomography results to divide into three groups; (a) local and/or lymph node metastasis without bone metastasis (n = 10), (b) <6 bone metastasis sites (n = 16), (c) ≥6 bone metastasis sites and/or visceral metastasis (n = 16), cancer-specific survival showed significant stratification (P < 0.001). 11 C-choline-positron emission tomography/computed tomography may reflect castration-resistant prostate cancer metastatic lesion activity for treatment response and prognosis evaluations.

Staying alive enhances both women's and men's fitness. We argue that Benenson et al. need to consider not only sex differences in the effects of care on offspring survival but also in age-specific fertility when predicting how longevity affects fitness. We review evidence that staying alive has important effects on both women's and men's fitness, and encourage consideration of alternative explanations for observed sex differences in threat responses.

Women take risks to help others to stay alive. Evidence that women voluntarily expose themselves to some threats more than men do challenges the generalizability of the claim that women exceed men in self-protective responses. Examples include women's higher rates of living organ donation and rescuing Jews during the holocaust. In general, women's efforts to keep other people alive can take precedence over their efforts to protect themselves.

The pregnancy compensation hypothesis, not the staying alive theory, accounts for disparate autoimmune functioning of women around the world. The pregnancy compensation hypothesis provides a mechanistic explanation for the evolution of sex differences in immune system functioning, the excess of women experiencing autoimmune disease, and why this is observed only in industrialized nations; none of which can be explained by the staying alive theory, as proposed by the authors of the target article.

Negative symptoms, striatal dopamine and model-free reward decision-making in schizophrenia. Negative symptoms, such as lack of motivation or social withdrawal, are highly prevalent and debilitating in patients with schizophrenia. Underlying mechanisms of negative symptoms are incompletely understood, thereby preventing the development of targeted treatments. We hypothesized that in patients with schizophrenia during psychotic remission, impaired influences of both model-based and model-free reward predictions on decision-making ('reward prediction influence', RPI) underlie negative symptoms. We focused on psychotic remission, because psychotic symptoms might confound reward-based decision-making. Moreover, we hypothesized that impaired model-based/model-free RPIs depend on alterations of both associative striatum dopamine synthesis and storage (DSS) and executive functioning. Both factors influence RPI in healthy subjects and are typically impaired in schizophrenia. Twenty-five patients with schizophrenia with pronounced negative symptoms during psychotic remission and 24 healthy controls were included in the study. Negative symptom severity was measured by the Positive and Negative Syndrome Scale negative subscale, model-based/model-free RPI by the two-stage decision task, associative striatum DSS by 18F-DOPA positron emission tomography and executive functioning by the symbol coding task. Model-free RPI was selectively reduced in patients and associated with negative symptom severity as well as with reduced associative striatum DSS (in patients only) and executive functions (both in patients and controls). In contrast, model-based RPI was not altered in patients. Results provide evidence for impaired model-free reward prediction influence as a mechanism for negative symptoms in schizophrenia as well as for reduced associative striatum dopamine and executive dysfunction as relevant factors. Data suggest potential treatment targets for patients with schizophrenia and pronounced negative symptoms.

A novel nano material for anti-cerebral ischaemia: preparation and application of borneol angelica polysaccharide liposomes. To investigate the preparation of novel nanoliposomes (Borneol Angelica Polysaccharide Liposomes, BAPL) for anti-cerebral ischaemia and verify its curative effects and mechanism. By applying a uniform experiment design to investigate the fitting combination of BAPL. Encapsulation Efficiency Evaluation of BAPL Preparation; Particle Size and Surface Potential Evaluation of BAPL Biological activity; Cerebral ischaemia models of rats Evaluation of BAPL curative effects and mechanism. (1) The fitting combination of lecithin, Cholesterol, AP mass and the borneol mass was 60 mg, 60 mg, 45 mg and 5 mg. the highest encapsulation efficiency was 80.4%, the particle size was 179.1 nm, and the surface zeta potential was -17.2 mV. It conforms to the nano-material standards. (2) The results of animal experiments show that: In the BAPL group, the infarct volume of TTC staining was significantly decreased, and the expression levels of NF-κBp65, TLR-4, IL-8, IL-6, IL-1β in brain tissue were significantly decreased, while the expression levels of ZO-1, ZO-2, IL-10 were significantly increased after cerebral ischaemia-reperfusion. BAPL is a novel nano and effective material for anti-cerebral ischaemia.

Beyond individual sex differences: "Staying alive theory" as an adaptive complex. Extended staying alive theory (SAT) raises the issue of the extent to which its various attributes are linked or whether they provide alternative means to the same adaptive ends. Theories such as SAT that consider an array of sex differences may benefit from the application of the multivariate D statistic, rather than using a series of d values, as is common at present.

Sex-dependent selection, ageing, and implications for "staying alive". Incorporating theoretic insights from ageing biology could advance the "staying alive" hypothesis. Higher male extrinsic mortality can weaken selection against ageing-related diseases and self-preservation, leading to high male intrinsic mortality. This may incidentally result in female-biased longevity-promoting traits, a possibility that will require rigorous testing in order to disentangle from the adaptive self-preservation hypothesis presented in the target article.

Alignment and impact angular dependence to O2 sticking and dissociation on Pt(111) and close-packed steps. Oxygen's interaction with Pt surfaces serves as a model system in the development of an accurate theoretical description of reaction mechanisms that involve multiple precursor states. To benchmark the influence of surface structure on the dynamics of this interaction, we report absolute values of the initial sticking probability of O2 onto Pt(111) and two vicinal surfaces for state-selected and rotationally-aligned O2 molecules. Sticking probabilities vary significantly for helicoptering and cartwheeling molecules. Our data can be understood if normal energy scaling holds for all molecular orientations relative to the surface. Vicinal surfaces are much more reactive than Pt(111) with little to no dependence on the molecule's alignment and a more complex angular dependence. At low incident energies, sticking probabilities are highest for incidence into step facets. The weak alignment dependence points toward predominant scattering into a physisorbed state preceding chemisorbed states over a wide angular range.

Self-Assembly Anchored Cationic Copolymer Interfaces for Applying the Control of Counterion-Induced Bacteria Killing/Release Procedure. In recent years, daily hygiene and disease control issues have received increasing attention, especially the raging epidemics caused by the spread of deadly viruses. The construction of the interface of new polymer materials is focused on, which can provide a cyclic operation process for the killing and releasing of bacteria, and perform repeated regeneration, which is of great significance for the development of advanced medical biomaterials. In order to explore the basic physical phenomena of bacterial attachment and detachment on the polymer material interface by different amine groups, this study plans to synthesize four different butyl methacrylate (BMA)-based cationic copolymers with primary, ternary, and quaternary amine groups, and compare their effects on bactericidal efficiency. Since BMA can generate strong hydrophobic interactions with the benzene ring structure, this study used a polystyrene substrate to realize a self-assembled cationic copolymer interface for controlling the counterion-induced bacterial killing/release process. Furthermore, negatively charged ions are introduced to induce changes in the hydration capability of water molecules and control the subsequent bacterial detachment function. In this study, possible directions to answer and clarify the above concepts are proposed, and there is a basic reference principle that can lead to research work in macromolecular bioscience fields.

Microbiota in anorexia nervosa: potential for treatment. Anorexia nervosa (AN) is characterised by the restriction of energy intake in relation to energy needs and a significantly lowered body weight than normally expected, coupled with an intense fear of gaining weight. Treatment of AN is currently based on psychological and refeeding approaches, but their efficacy remains limited since 40% of patients after 10 years of medical care still present symptoms of AN. The intestine hosts a large community of microorganisms, called the "microbiota", which live in symbiosis with the human host. The gut microbiota of a healthy human is dominated by bacteria from two phyla: Firmicutes and, majorly, Bacteroidetes. However, the proportion in their representation differs on an individual basis and depends on many external factors including medical treatment, geographical location and hereditary, immunological and lifestyle factors. Drastic changes in dietary intake may profoundly impact the composition of the gut microbiota, and the resulting dysbiosis may play a part in the onset and/or maintenance of comorbidities associated with AN, such as gastrointestinal disorders, anxiety and depression, as well as appetite dysregulation. Furthermore, studies have reported the presence of atypical intestinal microbial composition in patients with AN compared with healthy normal-weight controls. This review addresses the current knowledge about the role of the gut microbiota in the pathogenesis and treatment of AN. The review also focuses on the bidirectional interaction between the gastrointestinal tract and the central nervous system (microbiota-gut-brain axis), considering the potential use of the gut microbiota manipulation in the prevention and treatment of AN.

Females undergo selection too. Extending Campbell's (1999) staying alive theory (SAT) beyond aggression, we reviewed evidence that females are more self-protective than males. Many commentators provided additional supporting data. Sex differences in life-history adaptations, in the optimal relation between survival and reproduction, and in the mechanisms underlying trade-offs involved with self-protection remain important topics with numerous opportunities for improved understanding.

Surface Doping of Anionic Clusters Facilitated Direct Fabrication of Commercial Cellulose Nanofibrils for Long-Range Ordered Layer Structures. The fabrication of commercial cellulose nanofibrils (CNFs) into arrays with long-range ordering is of great significance for their extended applications, which, however, is severely hindered by their high disorder, aggregation, and hornified features. Herein, sub-nanoscale anionic metal oxide clusters (phosphotungstic acid, H3PW12O40, PTA) are applied to complex with commercial CNFs (dried powder DCNF and aqueous suspension WCNF) in aqueous media, and a long-range ordered layer structure can be facilely fabricated via typical unidirectional freezing. The surface complexation of the commercial CNFs and PTA can be confirmed through the small-angle scattering studies of the complex hydrogels. The hydrogels present similar correlation lengths in small-angle X-ray and neutron scattering measurements, suggesting the homogeneous distribution of PTA along the commercial CNFs. This gives rise to the negatively charged surface feature and further leads to strong repulsion among the commercial CNFs. Due to the disparity in sizes, the influence of PTA on the density of hydrogel networks is suppressed, and the network density is mainly dependent on the mass content of CNFs. The studies provide guidance to fabricate hydrogels with catalytic and photosensitive properties and also to design and stabilize long-range ordered structured aerogels during the removal of the nonfreezing bound water absorbed by the commercial CNFs after unidirectional freezing. This facile strategy shows great potential to broaden the application of commercial CNFs in thermal insulators, super-adsorbent materials, and supercapacitors in electrical devices.

Distinct movement disorders in contactin-associated-protein-like-2 antibody-associated autoimmune encephalitis. Autoimmune encephalitis can be classified into antibody-defined subtypes, which can manifest with immunotherapy-responsive movement disorders sometimes mimicking non-inflammatory aetiologies. In the elderly, anti-LGI1 and contactin associated protein like 2 (CASPR2) antibody-associated diseases compose a relevant fraction of autoimmune encephalitis. Patients with LGI1 autoantibodies are known to present with limbic encephalitis and additionally faciobrachial dystonic seizures may occur. However, the clinical spectrum of CASPR2 autoantibody-associated disorders is more diverse including limbic encephalitis, Morvan's syndrome, peripheral nerve hyperexcitability syndrome, ataxia, pain and sleep disorders. Reports on unusual, sometimes isolated and immunotherapy-responsive movement disorders in CASPR2 autoantibody-associated syndromes have caused substantial concern regarding necessity of autoantibody testing in patients with movement disorders. Therefore, we aimed to systematically assess their prevalence and manifestation in patients with CASPR2 autoimmunity. This international, retrospective cohort study included patients with CASPR2 autoimmunity from participating expert centres in Europe. Patients with ataxia and/or movement disorders were analysed in detail using questionnaires and video recordings. We recruited a comparator group with anti-LGI1 encephalitis from the GENERATE network. Characteristics were compared according to serostatus. We identified 164 patients with CASPR2 autoantibodies. Of these, 149 (90.8%) had only CASPR2 and 15 (9.1%) both CASPR2 and LGI1 autoantibodies. Compared to 105 patients with LGI1 encephalitis, patients with CASPR2 autoantibodies more often had movement disorders and/or ataxia (35.6 versus 3.8%; P < 0.001). This was evident in all subgroups: ataxia 22.6 versus 0.0%, myoclonus 14.6 versus 0.0%, tremor 11.0 versus 1.9%, or combinations thereof 9.8 versus 0.0% (all P < 0.001). The small group of patients double-positive for LGI1/CASPR2 autoantibodies (15/164) significantly more frequently had myoclonus, tremor, 'mixed movement disorders', Morvan's syndrome and underlying tumours. We observed distinct movement disorders in CASPR2 autoimmunity (14.6%): episodic ataxia (6.7%), paroxysmal orthostatic segmental myoclonus of the legs (3.7%) and continuous segmental spinal myoclonus (4.3%). These occurred together with further associated symptoms or signs suggestive of CASPR2 autoimmunity. However, 2/164 patients (1.2%) had isolated segmental spinal myoclonus. Movement disorders and ataxia are highly prevalent in CASPR2 autoimmunity. Paroxysmal orthostatic segmental myoclonus of the legs is a novel albeit rare manifestation. Further distinct movement disorders include isolated and combined segmental spinal myoclonus and autoimmune episodic ataxia.

Engineering Antimicrobial Polymer Nanocomposites: In Situ Synthesis, Disruption of Polymicrobial Biofilms, and In Vivo Activity. The increasing incidence of microbial infections and a limited arsenal of effective antibacterial and antifungal agents have entailed the need for new broad-spectrum therapeutics. Polymer-inorganic nanocomposites have emerged as an integral choice of antimicrobials but are limited by complicated synthesis, narrow-spectrum activity, and poor in vivo efficacy. Herein, chloride counterions of a nontoxic, moderately antibacterial polymer have been explored for in situ nanoprecipitation-based synthesis of water-soluble polymer-silver chloride nanocomposites. With the controlled release of silver ions, the nanocomposites were highly active against multidrug-resistant bacteria as well as fluconazole-resistant fungi. Alongside the elimination of metabolically inactive bacterial cells, the nanocomposites disrupted polymicrobial biofilms, unlike antibiotics and only silver-based ointments. This underlined the role of the engineered composite design, where the polymer interacted with the biofilm matrix, facilitating the penetration of nanoparticles to kill microbes. Further, the nanocomposite diminished Pseudomonas aeruginosa burden in mice skin infection (>99.9%) with no dermal toxicity proving its potential for clinical translation.

Nitroxyl radical-containing flexible porous coordination polymer for controllable size-aelective aerobic oxidation of alcohols. The ability of flexible porous coordination polymers (PCPs) to change their structure in response to various stimuli has not been exploited in the design of tunable-selectivity catalysts. Herein, we make use of this ability and prepare nitroxyl radical-containing flexible PCP that can reversibly switch between large- and contracted-pore configurations in response to solvent change and thus promote the controllable size-selective aerobic oxidation of alcohols.

Ensemble latent assimilation with deep learning surrogate model: application to drop interaction in a microfluidics device. A major challenge in the field of microfluidics is to predict and control drop interactions. This work develops an image-based data-driven model to forecast drop dynamics based on experiments performed on a microfluidics device. Reduced-order modelling techniques are applied to compress the recorded images into low-dimensional spaces and alleviate the computational cost. Recurrent neural networks are then employed to build a surrogate model of drop interactions by learning the dynamics of compressed variables in the reduced-order space. The surrogate model is integrated with real-time observations using data assimilation. In this paper we developed an ensemble-based latent assimilation algorithm scheme which shows an improvement in terms of accuracy with respect to the previous approaches. This work demonstrates the possibility to create a reliable data-driven model enabling a high fidelity prediction of drop interactions in microfluidics device. The performance of the developed system is evaluated against experimental data (i.e., recorded videos), which are excluded from the training of the surrogate model. The developed scheme is general and can be applied to other dynamical systems.

An integrated magneto-opto-fluidic biosensor for rapid on-chip assay of respiratory viruses of livestock. Respiratory disease is one of the most important causes of economic loss in swine production. In the USA, porcine reproductive and respiratory syndrome virus (PRRSV) and influenza A virus (IAV) are currently the top two primary viruses causing swine respiratory diseases. The commonly used PCR-based virus detection methods require virus extraction, nucleic acid purification, and detection, which are relatively time-consuming and expensive. This work reports an integrated magneto-opto-fluidic (iMOF) platform, in which antibody functionalized magnetic nanoparticles (MNPs) can enable efficient enrichment of multiple swine respiratory viruses and a photonic crystal (PC) biosensor can transduce the amount of captured MNP-virus nanoparticles to the change of their reflection signatures. Owing to the high refractive index of Fe2O3 MNPs, the use of MNPs can significantly enhance the PC sensor output. The proof-of-concept validation involves using antibody-functionalized MNPs to recognize IAV and PRRSV and transferring the formed MNP-virus conjugates onto the surface of the PC biosensors to quantify these viruses. The iMOF platform offers a high sensitivity of 3.5 TCID50 mL-1 and 5.9 TCID50 mL-1 for detecting IAV and PRRSV, respectively, and a rapid turnaround within one hour, including the MNP-virus conjugation, enrichment, and detection. The on-chip virus platform has a great potential for in-field surveillance of viral infections.

Acetylcholinesterase inhibitors from Conocarpus lancifolius Engl. (Combretaceae). Conocarpus lancifolius Engl. (Combretaceae) has several potential health-promoting effects, such as antidiabetic, antimicrobial, antioxidant, and cytotoxic effects. Phytochemical study of the ethyl acetate fraction of the leaf extract of this plant led to the isolation and identification of eight compounds viz., gallic acid (1), dihydromyricetin (2), myricetin (3), daucosterol (4), syringetin 3-O-β-D-glucopyranoside (5), quercetin 3-O-β-D-glucoside (6), gallocatechin (7), and (-)-epigallocatechin-3-O-gallate (8). Their acetylcholinesterase (AChE) in vitro and in silico inhibitory activities were evaluated. Daucosterol (4) showed the highest activity (IC50 0.316 μM) which was further validated by the superimposed docking orientation with the co-crystallized inhibitor, donepezil.

Matching-adjusted indirect comparison of efficacy outcomes in trials of calcipotriol plus betamethasone dipropionate foam and cream formulations for the treatment of plaque psoriasis. Once-daily, fixed-combination calcipotriol 50 μg/g (Cal) plus betamethasone dipropionate 0.5 mg/g (BD) is available in aerosol foam and cream formulations. As no head-to-head data are available, we use a matching-adjusted indirect comparison (MAIC) approach to compare Cal/BD foam and cream. Anchored and unanchored MAIC analyses were conducted using individual patient data (IPD) from five Cal/BD foam trials and two trials of Cal/BD cream. Outcomes of interest were the proportion of patients with Physician's Global Assessment (PGA) success and the mean reduction in modified Psoriasis Area and Severity Index (mPASI). In the anchored MAIC, patients were more likely to achieve PGA success after 4 weeks of Cal/BD foam than after 8 weeks of Cal/BD cream and had larger mean improvements in mPASI (p < .01 in EU mPASI analysis). In unanchored analyses, 4 weeks of Cal/BD foam treatment was statistically significantly more efficacious in inducing PGA success than 8 weeks of Cal/BD cream (p < .01 in five of six comparisons). Mean reductions in mPASI were consistently statistically significantly greater with Cal/BD foam than with Cal/BD cream. Use of Cal/BD foam consistently shows significantly greater improvements in PGA and mPASI outcomes, compared with Cal/BD cream.

Strategies for the treatment of acute benzodiazepine toxicity in a clinical setting: the role of antidotes. Although not a potentially life-threatening poisoning, benzodiazepine (BZD) intoxication may be life-threatening in special situations/populations or those with background diseases. The aim of this review is to evaluate all possible treatment options available in the literature for the management of benzodiazepine poisoning with special attention to antidote administration. We conducted a literature search using PubMed, Google Scholar, EMBASE, and Cochrane central register from 1 January 1980 to 10 November 2021 using keywords 'benzodiazepine,' 'poisoning,' 'toxicity,' 'intoxication,' and 'treatment.' Careful patient selection, ideally by a clinical toxicologist, may decrease the complications of flumazenil and add to its efficacy. The cost-to-benefit ratio should be considered in every single patient who is a candidate for flumazenil administration. In case a decision has been made to administer flumazenil, careful consideration of the possible contraindications is essential. We recommend slow administration of low doses of flumazenil (0.1 mg/minute) to avoid complications or withhold the administration with development of first signs of adverse effects. The main treatment of benzodiazepine toxicity is conservative with administration of activated charcoal, monitoring of the vital signs, prevention of aspiration and development of deep vein thrombosis due to prolonged immobilization, and respiratory support.

Systematic characterisation of the effective components of five Callicarpa species with UPLC-Q-TOF-MS and evaluation of their anti-hyperuricaemic activity. Callicarpa kwangtungensis (C. Kw), C. macrophylla (C. Ma), C. nudiflora (C. Nu), C. formosana (C. Fo), and C. kochiana (C. Ko) were medicinal plant resource in China. In this study, the UPLC/Q-TOF-MS analysis was performed and 151 compounds were identified. PCA analysis metabolic profiles of C. Nu, C. Ko and C. Kw leaves differ significantly from the other two Callicarpa species, while C. Fo and C. Ma share similar chemical constituents. OPLS-DA highlight with an S-plot indicated that there are 14 robust known chemical markers enabling the differentiation between these five Callicarpa plants. C. Ma, C. Nu, and C. Fo leaves extracts treatment effectively reversed the body weight loss, uric acid and creatinine content, hepatic XOD activity, kidney, liver, and ankle tissues injury and inflammation induced by potassium oxonate in hyperuricemia mice. While Ko and C. Kw leaves extracts treatment showed less improvement in hyperuricemia mice.

NUV-pumped red-emitting Ca9MnK(PO4)7 phosphor: energy transfer and charge compensation. The development of novel Mn-based phosphor hosts has received increasing interest in the search for highly efficient red emitting phosphors for white LED applications. In this study, Ca9MnK(PO4)7, a compound with the β-Ca3(PO4)2-type structure, was successfully synthesized by a high-temperature solid-state reaction process. The Eu2+-doped Ca9MnK(PO4)7 phosphor exhibits a broadband red emission peaking at 650 nm. The optimal excitation wavelength is 395 nm, which matches that of commercial ultraviolet (NUV) chips. Codoping Ce3+ ions into the Ca9MnK(PO4)7:Eu2+ phosphor efficiently improves Mn2+ luminescence. Here, Ce3+ acts as a charge compensator rather than a sensitizer and substantially increases the effective number of Eu2+ and finally improves the red emission of Mn2+. The charge compensation mechanism is also verified by codoping some optically inert rare earth ions (Ln3+) including Y3+, La3+ and Gd3+. The results demonstrate that these developed Ca9MnK(PO4)7:Eu2+, Ln3+ phosphors have great potential for application in NUV-based white LEDs. The energy transfer approach combined with the charge compensation technique is valuable for improving the performance of the red-emitting Ca9MnK(PO4)7:Eu2+ phosphor, which can further be used in developing other Mn-based phosphors.

Positioning of tofacitinib in treatment of ulcerative colitis: a global perspective. Tofacitinib has emerged as a useful drug for the treatment of ulcerative colitis (UC). There is an unmet need for cost-effective, non-immunogenic drugs with a safe adverse effect profile to treat patients with ulcerative colitis. In the present review, we evaluate the available literature to inform the appropriate positioning of tofacitinib in the current drug landscape and identify subsets where its use should be done with caution. Tofacitinib is helpful in the treatment of patients where the standard conventional or biological therapies have failed or were not tolerated. With lower costs of the generic drug than the biologicals (or biosimilars), it could be an important therapy in low- to middle-income countries. The risk of infections, especially Herpes Zoster and tuberculosis, needs to be addressed before initiation. Tofacitinib should be avoided in patients with venous thromboembolism and cardiovascular disease risk factors. Due to limited evidence, the use is not recommended in pregnancy, while it should be used with caution in elderly citizens. Future trials should look into the head-to-head comparison of tofacitinib with biologicals. The role of tofacitinib in acute severe colitis needs evaluation with comparative trials with current standards of care.

Decoupling Contact and Rotary Triboelectrification vs Materials Property: Toward Understanding the Origin of Direct-Current Generation in TENG. Direct-current (DC) triboelectric nanogenerators (TENGs) are increasingly recognized as next-generation power sources for widespread applications. Research has recently focused on developing novel materials as active layers for DC TENGs and device configurations to elucidate the working mechanisms. In this work, we report the use of a carbyne (dehydrohalogenated poly(vinylidene fluoride) (PVDF)) film as a positive-type friction layer for DC TENGs for efficient harvesting of rotary energy. The fabricated carbyne-based rotary TENG generates an output voltage (120 V) with excellent mechanical stability and peak power density (500 μW m-2). The mechanism of DC output generation from the carbyne-based rotary TENG is explained based on halogen removal from PVDF and the electrostatic breakdown effect. Additionally, the humidity effects on the fabricated carbyne-based rotary TENG toward a self-powered humidity sensor are studied in detail with the aid of in situ Raman analysis, Fourier transform infrared spectroscopy, and open-circuit potential measurements. Together, our experimental results demonstrate that using carbyne as an active triboelectric layer for DC TENGs would greatly benefit the next generation of power devices.

Gambogic acid suppresses the pentose phosphate pathway by covalently inhibiting 6PGD protein in cancer cells. Whether or not the anticancer activity of gambogic acid is achieved via regulating the cellular metabolic process remains unclear. Here we report that gambogic acid suppresses the pentose phosphate pathway (PPP) by covalently inhibiting the 6-phosphogluconate dehydrogenase (6PGD) protein. This study elucidates the mechanism of action of gambogic acid from the perspective of metabolic reprogramming regulation in cancer cells.

183W Nuclear Magnetic Resonance and Photocatalysis Studies of Two Ruthenium-Decorated Isopolyoxometalates {Ru2W10} and {Ru2W13} via pH-Induced Assemblies. Two structurally intriguing Ru-containing isopolyoxometalates [(Ru(OH))2O(W5O18)2]8- (1) and [(W5O18)(Ru2W8O31)]12- (2) were constructed from subtly different conditions. Single-crystal X-ray diffraction indicated that the precise pH modification has allowed us to trap a diruthenium-oxo core within different isopolyoxotungstate species. Compound 1 is the first sandwich-type ruthenium isopolyoxotungstate consisting of a linear {(HO)Ru-O-Ru(OH)} unit and two Lindqvist-type {W5} building blocks, while a ligand replacement of {W5} with an unusual {W8} ring in the case of compound 1 produced a unique embedded-type compound 2 with a quasi-linear {Ru-O-Ru} core. In addition to being determined in the solid state, crystal structures of 1 and 2 were also confirmed by 183W nuclear magnetic resonance (NMR) spectroscopy and electrospray ionization-mass spectrometry (ESI-MS) in solution. 183W NMR spectrum demonstrated that the two-line pattern of 1 (with approximately 4:1 relative intensities) is consistent with the pseudo-D2h symmetry observed in the solid state. However, two other lines were observed in 2 according to the C2v symmetry but not in accord with the expected 4/4/4/1 ratio in the crystalline state, which indicated that the structure of 2 could not be maintained completely in aqueous solution. After recrystallizing the solid sample of 2 in water, the crystal structure of 2 partly converted to the structure of 1, and the transformation was determined by the combined results of 183W NMR, ESI-MS and single-crystal X-ray diffraction measurements. Catalytic investigations showed that their sodium salts presented excellent photocatalytic activities toward the benzylamine oxidation reaction induced by visible light (λ > 400 nm). The structures of the two compounds can still be maintained without a significant yield decrease after five continuous reaction cycles. Furthermore, both catalysts 1 and 2 could proceed with the oxidative coupling reaction smoothly for most of the primary benzylamine derivatives bearing various functional groups (H, F, Cl, Br, and Me) in good to excellent yields.

Association of Nap Frequency With Hypertension or Ischemic Stroke Supported by Prospective Cohort Data and Mendelian Randomization in Predominantly Middle-Aged European Subjects. The aim of this study was to investigate the association between daytime napping frequency and the incidence of essential hypertension or stroke as well as to validate causality in this relationship via Mendelian randomization (MR). We conducted Cox regression analysis on 358 451 participants free of hypertension or stroke from UK Biobank. To validate the results of the observational analysis, we conducted a 2-sample MR for daytime napping frequency (123 single-nucleotide polymorphisms) with essential hypertension in FinnGen Biobank, stroke, and ischemic stroke in MEGASTROKE consortium and performed a corresponding 1-sample MR on the UK Biobank data. Compared with never napping, usually napping was associated with a higher risk of essential hypertension (hazard ratio, 1.12 [95% CI, 1.08-1.17]), stroke (hazard ratio, 1.24 [95% CI, 1.10-1.39], and ischemic stroke (hazard ratio, 1.20 [95% CI, 1.05-1.36]) in our prospective observational analysis. Both the 1-sample and 2-sample MR results indicated that increased daytime napping frequency was likely to be a potential causal risk factor for essential hypertension in FinnGEN (odds ratio, 1.43 [95% CI, 1.06-1.92]) and UK Biobank (odds ratio, 1.40 [95% CI, 1.28-1.58]). The 2-sample MR results supported the potential causal effect of nap frequency on ischemic stroke in MEGASTROKE (odds ratio, 1.29 [95% CI, 1.04-1.62]). Prospective observational and MR analyses provided evidence that increased daytime nap frequency may represent a potential causal risk factor for essential hypertension. The potential causal association of increased nap frequency with ischemic stroke was supported by 2-sample MR and prospective observational results.

Mental Illness and Racial Disparities in Correctional Staff-Involved Violence: An Analysis of Jails in the United States. In this study, we draw on theories of opportunity and focal concerns to examine how mental illness and race correspond to correctional staff-involved violence, particularly within the transient and diverse context of jails. Using a sample of 3,936 people incarcerated in jails from the 2011 to 2012 National Inmate Survey (NIS-3), we analyze how an individual's mental health status (number of mental illness diagnoses) and race relates to the risk of staff-inflicted victimization. Using a series of Firth's logistic regression models, we find that Black and Hispanic individuals are much more likely to be victims of correctional staff assault than their White counterparts. Those with one and two or more mental illness diagnoses are also at greater risk for staff-involved violence, respectively. Supplementary models show that those who suffer from serious mental illness are at particularly high risk for staff victimization. In a subsequent moderation analysis, we find that race does not condition the influence of mental health diagnoses on risk for staff-involved violence. Our findings reinforce the need for more research on correctional staff-involved violence and the implications of this research support calls for enhanced training of correctional staff regarding mental illness and racial bias.

Nurse Managers' Leadership, Patient Safety, and Quality of Care: A Systematic Review. This review examined relationships between nurse unit managers' leadership and patient safety and quality of care outcomes in hospital settings. Employing four databases (CINAHL, Embase, PubMed, and Web of Science) and ancestry searches, we identified 14 English-language, peer-reviewed, primary studies that examined such relationships using quantitative analyses. The studies were published between 2012 and 2021, and most used a cross-sectional design. Each study's quality was assessed using the Mixed-Method Appraisal Tool. In synthesizing results by categorizing outcomes, we found a positive trend in associations between effective nurse unit manager leadership and better outcomes, including fewer patient adverse events, increased nurse error reporting, and higher patient satisfaction and care quality. However, the heterogeneity of leadership measurement approaches and outcomes limited integration of study findings. Future researchers should clearly define study concepts to support interpretation of their findings and should use a suitable theoretical framework to help determine appropriate units of analysis.

Treatment of Resistant Acne Vulgaris in Adolescents Using Dietary Supplementation with Magnesium, Phosphate and Fatty Acids (Omega 6 and 7): Comparison with 13-Cis-Retinoic Acid. The burden of disease associated with acne vulgaris has continued to increase over time in the world population. This continued growth suggests that there is an unmet dermatologic need for this condition worldwide. Potential sequelae of acne, such as scarring, depigmentation, and marked emotional and psychological problems (e.g., low self-esteem), can lead to significant morbidity. The purpose of this study was to investigate whether dietary supplementation with magnesium, phosphate, omega 6 (linoleic acid calcium salt - C18:2 fatty acid Ca salt), and omega 7 (palmitoleic acid calcium salt - C16:1 fatty acid Ca salt) would help patients with acne vulgaris, and to compare with isotretinoin (13-cis retinoic acid). Magnesium has anti-inflammatory properties. Linoleic and palmitoleic acids have bactericidal activity against Staphylococcus aureus and Cutibacterium acnes (formerly known as Propionibacterium acnes). A single-blind randomized study was conducted in which 257 patients were treated with the above dietary supplementation (group A) and 275 patients with isotretinoin (group B) for 6 months. All patients in group A (100%) reported complete regression of symptoms after 6 months of treatment. On the other hand, 187 subjects (68%) in group B reported complete resolution of symptoms during the same period. The difference between the groups (p < 0.05) was statistically significant. The study was approved by the CEP/CONEP. This natural formulation promotes regression and/or cure of acne vulgaris symptoms and has better results than drugs (such as isotretinoin), without significant side effects.

Tuning the aqueous self-assembly of porphyrins by varying the number of cationic side chains. Due to their excellent electronic and optical properties, porphyrins are extensively studied conjugated macrocycles in supramolecular chemistry for assembling functional nanomaterials. Although the aggregation of monomers plays a significant role in driving the self-assembly process into ordered nanostructures, it remains a challenge for tuning the self-assembling behavior of porphyrins through molecular structure modifications, especially in aqueous solutions. In the present work, two novel water-soluble porphyrin derivatives were synthesized by introducing cationic linear side chains into the π-conjugated core for phosphate-templated assembly through electrostatic interactions. It was found that the stacking patterns (H- or J-type aggregation) of porphyrins could be tuned by varying the number of side chains, which are associated with dramatic morphological change. The cytotoxicity and photodynamic properties of the J-aggregation-driven nano-assemblies were also investigated for the purpose of anti-cancer treatment. This study demonstrates a facile and effective strategy to regulate the aqueous self-assembling behavior of porphyrins that can impact the structure and properties of assembly, which will be of great benefit to the design and synthesis of functional nanomaterials for specific applications.

Mn(II) Oxidation by Free Chlorine Catalyzed by the Hydrolytic Products of Ferric and Aluminum Species under Drinking Water Conditions. Mn(II) oxidation by free chlorine can be applied to remove Mn(II) at water treatment plants. This reaction also results in particulate MnOx formation and accumulation in drinking water distribution systems. This study investigated the effect of Fe(III) and Al(III) hydrolysis products (mainly precipitates) on Mn(II) oxidation by free chlorine under drinking water conditions. The results showed that Fe3+ added as FeCl3 and Al(III) added as polyaluminum chloride (PACl) at tens to hundreds of micrograms per liter dramatically catalyzed Mn(II) oxidation by free chlorine. Through hydrolytic precipitation at circumneutral pH, Fe3+ and Al13 (the dominant preformed Al species in PACl) generated Fe(OH)3-like particles and Al13 aggregates, respectively, which initiated heterogeneous Mn(II) oxidation. Kinetic modeling indicated that, once some MnOx was formed, MnOx and Fe(OH)3 catalyzed the subsequent Mn(II) oxidation to an equal extent. The particles (aggregates) formed from Al13 species exhibited a weaker catalytic capacity in comparison to MnOx and Fe(OH)3 at equivalent molar concentrations. Interestingly, unlike Al13 species in PACl, Al(III) added as AlCl3 had a negligible influence on Mn(II) oxidation, even when Al(OH)3(am) precipitates were formed. The catalytic effects of Fe3+ and Al13 hydrolysis products were confirmed by experiments with natural water and finished water, and the lower Mn(II) oxidation rate was mainly attributed to organic matter.

On the risk of secondary cancer from thymoma radiotherapy. Objective.This study aims at quantifying the lifetime attributable risk of secondary fatal cancer (LARFAC) to patients receiving adjuvant radiotherapy treatment for thymoma, a neoplasm where cure rates and life expectancy are relatively high, patient age at presentation relatively low and indications for radiotherapy controversial depending on the disease stage.Approach.An anthropomorphic phantom was scanned, organs were contoured and a standard 6 MV 3DCRT treatment plan was produced for thymoma treatment. The phantom was loaded with thermoluminescent dosimeters (TLDs) and treated by linear accelerator per plan. The TLDs were subsequently read for out-of-field dose distribution while in-field dose distribution was obtained from the planning system. Sex and age-specific lifetime radiogenic cancer risk was calculated as the sum of in-field risk and out-of-field risk. The latter risk was estimated using hybrid ICRP 2007 103-BEIR VII tables of organ-specific risks based on the linear-no threshold (LNT) model and applicable at low doses, while the former using mathematical risk models applicable at high doses.Main results.The LARFAC associated with a prescribed dose of 50 Gy to target volume in 25 fractions was in the approximate range of 1%-3%. The risk was higher for young and female patients. The largest contributing organ to this risk were the lungs by far. Using the LNT model inappropriately to calculate risk at therapeutic doses (in-field) would overestimate the risk up to tenfold.Significance.The LARFAC to patient from thymoma radiotherapy was quantified taking into consideration the inapplicability of the LNT model at therapeutic doses. The risk is not negligible; the information may be relevant to patients and clinicians.

Optical Chemosensors based on Spiropyran-Doped Polymer Nanoparticles for Sensing pH of Aqueous Media. Photochromic polymers, which are prepared by the incorporation of photochromic compounds into polymer matrices, show fluorescence emission along with color change under UV light irradiation. Polymer nanoparticles yield high chromic properties at low chromophore loadings, as they have a large surface area to absorb a high level of light irradiation. Particle size is a significant parameter to control optical properties, where the decrease of particle size results in a high light absorption and efficiency of photochromism and fluorescence emission. Reverse atom transfer radical polymerization was used to synthesize methyl methacrylate homopolymer and its copolymers with different comonomers to yield polymers with a narrow molecular weight distribution. Spiropyran was doped to the polymeric nanoparticles during nanoprecipitation to yield photochromic polymer nanoparticles. Particle size below 100 nm for the photochromic nanoparticles was shown by dynamic light scattering. Morphology investigation with microscopic analysis showed spherical morphology for nanoparticles. The photochromic properties of the polymer nanocarriers were studied in both acidic and alkaline media. The results indicated that the pH of the media as well as the copolymer composition significantly affect the optical properties. Therefore, the photochromic polymer nanoparticles could have potential applications as optical pH chemosensors by colorimetric and fluorometric detection mechanisms. The nanoparticles with hydroxyl- or amine-functional groups were shown to be highly efficient for pH chemosensor applications. Finally, photochromic cellulosic papers prepared from the photochromic polymer nanoparticles were highly applicable in the detection of acid vapors.

Highly Thermoelectric ZnO@MXene (Ti3C2Tx) Composite Films Grown by Atomic Layer Deposition. Due to its unique high conductivity and flexibility, the two-dimensional MXene material (Ti3C2Tx) is expected to possess great potential in the thermoelectric field. However, the low thermoelectric performance from high thermal conductivity and a low Seebeck coefficient has limited its practical application. In this report, we demonstrate the uniform growth of ZnO layers on the laminar Ti3C2Tx membrane by atomic layer deposition (ALD). Benefiting from the low-temperature deposition characteristics of the ALD technique, the ZnO@Ti3C2Tx composite films maintain the basic apparent morphology of the original films after the deposition. We reveal that the Schottky barrier formed between ZnO and Ti3C2Tx exhibits an energy-filtering effect, significantly enhancing the Seebeck coefficient to result in more than a double increase in the power factor. Meanwhile, the strong phonon-interface scattering between ZnO and Ti3C2Tx is found to reduce the thermal conductivity of the composite films by a factor of four as compared to pure Ti3C2Tx ones, further improving the overall thermoelectric properties of the ZnO@Ti3C2Tx composite films. Our investigation provides an ALD-based strategy for growing wide band gap layers on the narrow band gap films to improve the thermoelectric performance of various MXene materials.

Measuring Stroke Quality: Methodological Considerations in Selecting, Defining, and Analyzing Quality Measures. Knowledge about stroke and its management is growing rapidly and stroke systems of care must adapt to deliver evidence-based care. Quality improvement initiatives are essential for translating knowledge from clinical trials and recommendations in guidelines into routine clinical practice. This review focuses on issues central to the measurement of the quality of stroke care, including selection and definition of quality measures, identification of the eligible patient cohorts, optimization of data quality, and considerations for data analysis and interpretation.

The Problem of Restrictive Thrombectomy Trial Eligibility Criteria. Since 2015, a series of endovascular trials transformed the management of patients with large vessel occlusion stroke. Most thrombectomy trials used restrictive eligibility criteria to optimize the chances of showing that thrombectomy could work. The problem arises when generalizing trial results into evidence-based recommendations. Many organizations, oblivious of this problem, translated verbatim restrictive trial eligibility criteria into authoritative guidelines, which limit the use of thrombectomy to highly selected patients. The clinical problem becomes as follows: what to do for all other stroke patients equally in need of care? The cycle of restrictive trial eligibility criteria, corresponding restrictive guidelines, observational studies of unvalidated practices showing other patients benefit, a new trial is needed, has been repeated often. Thrombectomy trials ought to have included all patients that could potentially benefit. If the signal that was looked for by restricting eligibility is at risk of being lost in the noise generated by the heterogeneity of patients, D. Sackett proposed a solution: to use the same criteria, not to select some patients and exclude others but to prespecify the subgroup of patients most likely to benefit. In this commentary, we propose a tiered approach, where the boundaries of treatment beneficiaries can be more rigorously tested and confirmed. Identification of these patients before the development of guidelines, which would have otherwise neglected these individuals, may open innumerable treatment opportunities to those who will instead be denied of them.

Effect of Intravenous Alteplase Treatment on First-Line Stent Retriever Versus Aspiration Alone During Endovascular Treatment. We aimed to assess whether the effect of intravenous alteplase treatment (IVT) before endovascular treatment (EVT) on outcome is modified by first-line technique during EVT in IVT eligible patients. This was a post hoc analysis from MR CLEAN-NO IV (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands - Intravenous Treatment Followed by Intra-Arterial Treatment Versus Direct Intra-Arterial Treatment for Acute Ischemic Stroke Caused by a Proximal Intracranial Occlusion), a randomized trial of IVT followed by EVT versus EVT alone in patients presenting directly to EVT-capable centers. We included data from all patients who underwent EVT with a thrombectomy attempt. We compared patients treated with stent retriever (with or without aspiration) to aspiration alone as first-line EVT technique and assessed the interaction of first-line EVT technique with IVT treatment. Primary outcome was the 90-day modified Rankin Scale score, analyzed with mixed model ordinal regression for a shift towards better outcome. Secondary outcomes included successful reperfusion (extended Thrombolysis in Cerebral Infarction score 2b-3). Of 473 included patients, 102 (21.6%) were treated with aspiration alone as first-line technique. In the full population, functional outcome was similar for patients treated with stent retriever versus aspiration only (adjusted common odds ratio [acOR]' 1.07 [95% CI, 0.69-1.66]). We observed a significant interaction between IVT and first-line EVT technique (P=0.03). In the aspiration-only group, patients treated with EVT alone had worse functional outcome compared to those treated with IVT and EVT (acOR, 0.44 [95% CI, 0.21-0.90]). In the stent retriever group, functional outcome did not differ between patients treated with or without IVT (acOR, 1.08 [95% CI, 0.74-1.57]). There was no statistically significant interaction for successful reperfusion. In MR CLEAN-NO IV, the treatment effect of IVT was modified by first-line EVT technique. Patients treated with aspiration only as first-line technique had worse clinical outcomes if they did not receive IVT. No such difference was observed in patients treated with stent retrievers. Confirmation by pooling with results from other trials is needed to confirm these findings.

Victim-Survivors' Prioritization of Reasons for Non-Reporting Adult Sexual Assaults to Law Enforcement. Despite the potential benefits of reporting a sexual assault to the police, few sexual assault victim-survivors choose to do so. Prior research on reasons for non-reporting has lacked American Indian/Alaska Native representation as well as a quantitative prioritization of non-reporting reasons. This study sought to fill those gaps by using quantitative data from 95 participants in an online, self-administered survey of victim-survivors of adult sexual assaults in Alaska. Descriptive, univariate results revealed great variation in the reasons for non-reporting. Further, which reasons were more commonly endorsed changed when measuring victim-survivor prioritization of reasons (primary, secondary, and tertiary) rather than simple endorsement. Lastly, there were few subgroup differences when conducting bivariate analyses using racial/ethnic identity and the act of reporting other adult sexual assaults in Alaska. The results of this study add to existing literature on non-reporting with an emphasis on changing how we measure the reasons behind non-reporting. The results also signal to criminal justice policy makers and practitioners that proactive, comprehensive efforts must be made to regain the faith and trust of current and potential victim-survivors so that they see the criminal justice system as a viable avenue for securing justice in ways that are meaningful to them.

Arabidopsis Glucan Synthase-Like1 (GSL1) Is Required for Tolerance to Low-Calcium Conditions and Exhibits a Function Comparable to GSL10. Crops that exhibit symptoms of calcium (Ca) deficiency constitute a major agricultural problem. Molecular breeding of resistant cultivars is a promising method for overcoming this problem. However, the involved genes must first be identified. Here, we show that the glucan synthase-like (GSL) 1 gene is essential for low-Ca tolerance in Arabidopsis thaliana. GSL1 is homologous to GSL10, which we previously showed was essential for low-Ca tolerance. Under low-Ca conditions, gsl1 mutants exhibit reduced growth and the onset of necrosis in new leaves. These symptoms are typical of Ca-deficient crops. A grafting experiment suggested that the shoot genotype, but not the root genotype, was important for the suppression of shoot necrosis. The ectopic accumulation of callose under low-Ca conditions was significantly reduced in gsl1 mutants compared with wild-type plants. Because the corresponding single-mutant phenotypes are similar, we investigated the interaction between GSL1 and GSL10 by testing the gsl1 gsl10 double mutant for sensitivity to low-Ca conditions. The double mutant exhibited a more severe phenotype than did the single mutants, indicating that the effects of GSL1 and GSL10 on low-Ca tolerance are additive. Because GSL genes are highly conserved within the plant kingdom, the GSL loci may be useful for breeding low-Ca tolerant crops.

The Effect of Intimate Partner Violence on Fear of Childbirth Among Pregnant Women. This study was conducted to determine the effect of intimate partner violence on childbirth fear of pregnant women. This descriptive and cross-sectional study included 335 pregnant women who applied to pregnant outpatient clinics. The data of the study were collected with Questionnaire Form and Wijma Birth Expectation/Experience Scale A Version (W-DEQ-A). Descriptive statistical methods, t-test, one-way ANOVA, Mann-Whitney U-test, and Kruskal-Wallis test were used in the analysis of the data. W-DEQ-A scale score of pregnant women was found to be 69.34 ± 29.37. It was found that 15.2% of pregnant women experienced "mild level" childbirth fear, 28.4% had "moderate level" childbirth fear, 26.6% had "severe level" childbirth fear, and 29.9% had "clinical level" childbirth fear. It was determined that 49.3% of pregnant women were exposed to any type of violence by their partners. It was found that pregnant women were exposed to 46% verbal violence, 23.9% emotional violence, 13.7% economic violence, 8.7% physical violence, and 2.1% sexual violence. When pregnant women experiencing any type of violence (p = .000), verbal violence (p = .000), emotional violence (p = .000), and economic violence (p = .000) were compared with pregnant women who did not experience violence, W-DEQ-A scores were higher and differences were statistically significant. It was determined to be statistically significant differences of W-DEQ-A scores according to the age of the pregnant women (p = .044), family type (p = .004), place of residence (p = .026), and psychological problems before pregnancy (p = .026). As a result, the rate of violence exerted by their intimate partners against pregnant women was high. In addition, intimate partner violence during pregnancy had negative effects on the fear of childbirth of pregnant women.

Stable Monodisperse Pb1-x Cdx S Quantum Dots for NIR-II Bioimaging by Aqueous Coprecipitation of Bimetallic Clusters. Aqueous lead sulfide (PbS) quantum dots (QDs) synthesized by traditional methods are unstable, so that they are usually coated with cadmium sulfide (CdS) to prevent oxidation, which are complicated and not satisfactory for mass production. Here, stable ternary Pb1-x Cdx S QDs were synthesized by in situ coprecipitation of Pb4-n Cdn O4 bimetallic clusters in an aqueous solution, which possess a uniform size of 4.0±0.2 nm and the second near-infrared (NIR-II) emission at 1100 nm with photoluminescence quantum yield (PLQY) as high as 17.72 %. Stored at 4 °C and in colloidal form, the PLQY of Pb1-x Cdx S QDs remained at 90.9 % of the initial value after 15 days, while stored as powder, the spectra did not change after 5 months. The high PLQY and good water compatibility of Pb1-x Cdx S QDs provide a good performance in vivo vasculature imaging and lymphatic system imaging at a very low power density (10 mW cm-2 ) in the NIR-II window.

In Situ Periodic Regeneration of Catalyst during CO2 Electroreduction to C2+ Products. Developing electrocatalytic reactions with high-efficiency can make important contributions to carbon neutrality. However, poor long-term stability of catalysts is a bottleneck for its practical application. Herein, an "in situ periodic regeneration of catalyst (PR-C)" strategy is proposed to give long-term high efficiency of CO2 electroreduction to generate C2+ products over Cu catalyst by applying a positive potential pulse for a short time periodically in the halide-containing electrolyte. The high Faradaic efficiency (81.2 %) and current density (22.6 mA cm-2 ) could be maintained completely at least 36 h, while the activity and selectivity decreased continuously without using the PR-C method. Control experiments and operando characterization demonstrated that the surface structure and oxidation state of Cu could be recovered periodically by the PR-C method, which was beneficial for CO2 activation and C-C coupling.

High-Risk Symptom Cluster Groups for Work-Life Quality and Turnover Intention among Nurses. This cross-sectional study aims to identify high-risk symptom cluster groups for assessing the quality of nursing work life (QNWL) and turnover intention among Korean nurses who have experienced workplace violence. Nurses were recruited for an online survey in May 2021 (n = 203). The following four symptom clusters are extracted: (a) depression-anxiety, (b) shame-somatization, (c) nightmare-loss of appetite, and (d) anger-shock. Three symptom cluster groups were identified. Group 1 had the highest score for the anger-shock symptom cluster, as well as the highest symptom scores and turnover intention. Group 2 had the highest score for the nightmare-loss of appetite symptom cluster and the lowest QNWL. Group 3 had a similar symptom cluster pattern to Group 1 but lower scores for all symptom clusters. Symptom monitoring and programs tailored to symptom cluster groups at the institutional level could be useful for managing QNWL and turnover intention.

Near-Infrared Fluorescent and Photoacoustic Dual-Mode Probe for Highly Sensitive and Selective Imaging of Cysteine In Vivo. Cysteine (Cys) plays an important role in many physiological activities of human beings. Various diseases are always accompanied by abnormal levels of Cys. A series of Cys-responsive probes were recently developed. However, most fluorescent probes have many disadvantages and exhibit poor in vivo imaging. Therefore, a near-infrared fluorescence (NIRF)/photoacoustic (PA) dual-mode probe with high selectivity and sensitivity (limit of detection = 10.6 nM) toward Cys was developed in this study. The new Probe I interacted with Cys to activate NIRF/PA signals, detecting Cys in vitro with a large emission wavelength (851 nm) and Stokes shift (191 nm), monitoring the occurrence of liver cancer in vivo. This work not only presented an effective NIRF/PA dual-mode dicyanoisophorone probe for the first time in the imaging of Cys but also provided a comprehensive and accurate tool for detecting different analytes and tumors in deeper tissues, which could be conducive to the early diagnosis of diseases.

Angelica gigas: Signature Compounds, In Vivo Anticancer, Analgesic, Neuroprotective and Other Activities, and the Clinical Translation Challenges. Angelica gigas Nakai (AGN) root is a medicinal herbal widely used in traditional medicine in Korea. AGN root ethanolic extract dietary supplements are marketed in the United States for memory health and pain management. We comprehensively reviewed the anticancer, analgesic, pro-memory and other bio-activities of AGN extract and its signature phytochemicals decursin, decursinol angelate, and decursinol a decade ago in 2012 and updated their anticancer activities in 2015. In the last decade, significant progress has been made for understanding the pharmacokinetics (PK) and metabolism of these compounds in animal models and single dose human PK studies have been published by us and others. In addition to increased knowledge of the known bioactivities, new bioactivities with potential novel health benefits have been reported in animal models of cerebral ischemia/stroke, anxiety, sleep disorder, epilepsy, inflammatory bowel disease, sepsis, metabolic disorders, osteoporosis, osteoarthritis, and even male infertility. Herein, we will update PK and metabolism of pyranocoumarins, review in vivo bioactivities from animal models and human studies, and critically appraise the relevant active compounds, the cellular and molecular pharmacodynamic targets, and pertinent mechanisms of action. Knowledge gaps include whether human pyranocoumarin PK metrics are AGN dose dependent and subjected to metabolic ceiling, or metabolic adaptation after repeated use. Critical clinical translation challenges include sourcing of AGN extracts, product consistency and quality control, and AGN dose optimization for different health conditions and disease indications. Future research directions are articulated to fill knowledge gaps and address these challenges.

Involvement of NGATHA-Like 1 Transcription Factor in Boron Transport under Low and High Boron Conditions. NGATHA-Like 1 (NGAL1) transcription factor has been identified as a gene regulated through AUG-stop-mediated boron (B)-dependent translation stall; however, its function in B response remains unknown. Here, we show that NGAL1 plays an important role in the maintenance of B transport under both low- and high-B conditions in Arabidopsis thaliana. NGAL1 mRNA is accumulated predominantly in shoots in response to B stress. Independent ngal1 mutants carrying transferred DNA (T-DNA) and Ds-transposon insertions exhibit reduced B concentrations in aerial tissues and produce shortened and reduced number of siliques when B supply is limited. Furthermore, the expression of B transporter genes including nodulin 26-like intrinsic protein 6; 1 (NIP6;1), NIP5;1, NIP7;1 and borate exporter 1 (BOR1) is significantly decreased in ngal1 mutants under low-B condition, suggesting that NGAL1 is required for the transcript accumulation of B transporter genes to facilitate B transport and distribution under B limitation. Under high-B condition, ngal1 mutants exhibit reduced growth and increased B concentration in their shoots. The accumulation of BOR4 mRNA, a B transporter required for B efflux to soil, is significantly reduced in roots of ngal1 plants under high-B condition, suggesting that NGAL1 is involved in the upregulation of BOR4 in response to excess B. Together, our results indicate that NGAL1 is involved in the transcriptional regulation of B transporter genes to facilitate B transport and distribution under both low- and high-B conditions.

Effective features extraction by analyzing heart sound for identifying cardiovascular diseases related to COVID-19: A diagnostic model. Incidence and exacerbation of some of the cardiovascular diseases in the presence of the coronavirus will lead to an increase in the mortality rate among patients. Therefore, early diagnosis of such diseases is critical, especially during the COVID-19 pandemic (mild COVID-19 infection). Thus, for diagnosing the heart diseases related to the COVID-19, an automatic, non-invasive, and inexpensive method based on the heart sound processing approach is proposed. In the present study, a set of features related to the nature of heart signals is defined and extracted. The investigated features included morphological and statistical features in the heart sound frequencies. By extracting and selecting a set of effective features related to the mentioned diseases, and avoiding to use different segmentation and filtering techniques, dependence on a limited dataset and specific sampling procedures has been eliminated. Different classifiers with various kernels are applied for diagnosis in data unbalanced and balanced conditions. The results showed 93.15% accuracy and 93.72% F1-score using 60 effective features in data balanced conditions. The identification system using the extracted features from Azad dataset is able to achieve the desired results in a generalized dataset. In this way, in the shortest possible sampling time, the present system provided an effective and generalizable method and a practical model for diagnosing important cardiovascular diseases in the presence of coronavirus in the COVID-19 pandemic.

Ancillary ligand-regulated Ti(IV)-based metallocalixarene coordination cages for photocatalytic H2 evolution. High-valence Ti(IV)-based metallocalixarene coordination cages that are linked by oriented ancillary ligands are unknown so far. Herein, the first family of tunable calixarene-based coordination cages of Ti(IV) with a framework formula [Ti12(OiPr)12(TBC[4])6L6] have been assembled from six {Ti2(OiPr)2(TBC[4])}2+ nodes and six pyridinedicarboxylic ligands. Furthermore, the {Ti12L6} cage showed strong photocatalytic H2 evolution activity, and DFT studies were performed to explore its electronic structure.

Lactobacillus Spp.-Enhanced Memory is Strain-Dependent and Associated, in Part, with Amyloidogenic and anti-Oxidant/Oxidative Stress Interplay in Amyloid Beta Precursor Protein Transgenic Mice. This study explored mechanisms underpinning enhanced memory in amyloid precursor protein (APP) transgenic mice (male; 10-12 months; n = 6/group) supplemented with Lactobacillus plantarum LAB12 (LAB12)/Lactobacillus casei Shirota (LcS). Morris Water Maze test was performed before brains were harvested for gene expression and biochemical studies. LAB-supplemented mice exhibited reduced escape latency and distance but significant increased time spent in platform zone. This was associated with downregulated beta-site APP cleaving enzyme-1 (BACE1) mRNA and significant reduced nitric oxide in brains. LAB12 also significantly increased glutathione. The LAB-enhanced memory is strain-dependent and could be mediated, in part, through amyloidogenic pathway and anti-oxidant/oxidative stress interplay.

CCN2 Facilitates IL-17 Production and Osteoclastogenesis in Human Osteoarthritis Synovial Fibroblasts by Inhibiting miR-655 Expression. Osteoarthritis (OA) is associated with extensive upregulation of osteoclastogenesis and subsequent bone breakdown. The CCN family protein connective tissue growth factor (CCN2, also called CCN2) enhances inflammatory cytokine production in OA disease. The cytokine interleukin (IL)-17 is known to induce osteoclastogenesis and bone erosion in arthritic disease. Our retrieval of data from the Gene Expression Omnibus (GEO) data set and clinical tissues exhibited higher CCN2 and IL-17 expression in OA synovial sample than in normal healthy samples. We observed the same phenomenon in synovial tissue from rats with anterior cruciate ligament transaction (ACLT)-elicited OA compared with synovial tissue from control healthy rats. We also found that CCN2 facilitated increases in IL-17 synthesis in human OA synovial fibroblasts (OASFs) and promoted osteoclast formation. CCN2 affected IL-17 production by reducing miR-655 expression through the ILK and Syk signaling cascades. Our findings improve our understanding about the effect of CCN2 in OA pathogenesis and, in particular, IL-17 production and osteoclastogenesis, which may help with the design of more effective OA treatments. © 2022 American Society for Bone and Mineral Research (ASBMR).

Gas phase acidity of water clusters. In the present work, we have estimated the gas-phase acidity of different water clusters, i.e., (H2O)n, n = 1-20, 30, 35, 42, 54, 80, and 100. The present work indicates that the gas-phase acidity of the terminal hydrogen atom increases with the size of water clusters and starts converging at (H2O)30. Furthermore, the present work also indicates that the gas-phase acidity of a terminal hydrogen atom is higher than that of the corresponding bulk hydrogen atom for the same size of water cluster.

Effects of Domestication on Plant-Microbiome Interactions. Through the process of domestication, selection is targeted on a limited number of plant traits that are typically associated with yield. As an unintended consequence, domesticated plants often perform poorly compared to their wild progenitors for a multitude of traits that were not under selection during domestication, including abiotic and biotic stress tolerance. Over the past decade, advances in sequencing technology have allowed for the rigorous characterization of host-associated microbial communities, termed the microbiome. It is now clear that nearly every conceivable plant interaction with the environment is mediated by interactions with the microbiome. For this reason, plant-microbiome interactions are an area of great promise for plant breeding and crop improvement. Here, we review the literature to assess the potential impact that domestication has had on plant-microbiome interactions and the current understanding of the genetic basis of microbiome variation to inform plant breeding efforts. Overall, we find limited evidence that domestication impacts the diversity of microbiomes, but domestication is often associated with shifts in the abundance and composition of microbial communities, including taxa of known functional significance. Moreover, genome-wide association studies and mutant analysis have not revealed a consistent set of core candidate genes or genetic pathways that confer variation in microbiomes across systems. However, such studies do implicate a consistent role for plant immunity, root traits, root and leaf exudates and cell wall integrity as key traits that control microbiome colonization and assembly. Therefore, selection on these key traits may pose the most immediate promise for enhancing plant-microbiome interactions through breeding.

Impact of worsening surgically induced chronic kidney disease (CKD-S) in preoperative CKD-naïve patients on survival in renal cell carcinoma. To evaluate effects of worsening surgically induced chronic kidney disease (CKD-S) on oncological and non-oncological survival outcomes in renal cell carcinoma (RCC). We performed a retrospective analysis of patients who underwent partial (PN) or radical nephrectomy (RN) and were free of preoperative CKD (estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m2 ). Patients were stratified by CKD stage at last follow-up: no CKD-S (eGFR ≥60 mL/min/1.73 m2 ), de novo CKD-S 3a (eGFR 45-59 mL/min/1.73 m2 ), CKD-S 3b (eGFR <45 and ≥30 mL/min/1.73 m2 ) and CKD-S 4 (eGFR <30 and ≥15 mL/min/1.73 m2 ). The primary outcome was all-cause mortality (ACM). Secondary outcomes included non-cancer mortality (NCM), cancer-specific mortality (CSM) and de novo CKD-S Stage 3/4. Multivariable analysis (MVA) was utilised to identify risk factors for outcomes. Kaplan-Meier analysis (KMA) was utilised to evaluate overall (OS), non-cancer (NCS), and cancer-specific survival with respect to CKD-S categories. We analysed 3239 patients. The mean preoperative and last-follow-up eGFRs were 87.4 and 69.5 mL/min/1.73 m2 , respectively. On last follow-up, 57.9% (n = 1876) had no CKD-S, 18.7% (n = 606) had CKD-S 3a, 15.1% (n = 489) had CKD-S 3b and 8.3% (n = 268) had CKD-S 4. On MVA, de novo CKD-S 3b and 4 were independently associated with ACM (hazard ratios [HRs] 1.3-2.1, P = 0.003-0.001) and NCM (HRs 1.5-2.8, P = 0.021-0.001), but not CSM (P = 0.219-0.909); de novo CKD-S 3a was not predictive for any mortality outcomes (P = 0.102-0.81). RN was independently associated with CKD-S 3-4 (HRs 1.78-1.99, P < 0.001-0.035). Comparing no CKD-S, CKD-S 3a, CKD-S 3b and CKD-S 4, KMA demonstrated worsening outcomes with progressive CKD-S stage: 5-year OS 84% vs 78% vs 71% vs 60% (P < 0.001) and 5-year NCS 93% vs 87% vs 83% vs 72% (P < 0.001). Development of CKD-S Stage 3b and 4, but not 3a, was associated with worsened ACM and NCM. The decision to proceed with nephron preservation via PN should be individualised based on oncological risk and risk of functional decline to CKD-S 3b or 4, and not CKD-S 3a.

Aging Effect, Reproducibility, and Test-Retest Reliability of a New Cerebral Amyloid Angiopathy MRI Severity Marker-Cerebrovascular Reactivity to Visual Stimulation. Decreased cerebrovascular reactivity, measured as changes in blood-oxygen-level-dependent (BOLD) signal, is a potential new cerebral amyloid angiopathy (CAA) severity marker. Before clinical application, the effect of aging on BOLD parameters, and reproducibility and test-retest reliability of these parameters should be assessed. Assess the effect of healthy aging on cerebrovascular reactivity (BOLD amplitude, time to peak, and time to baseline). And determine reproducibility and test-retest reliability of these parameters. Prospective-observational. Eighty-six healthy adults (mean age 56 years, 55% female), 10 presymptomatic D-CAA mutation carriers (mean age 34 years, 70% female), and 10 symptomatic D-CAA mutation carriers (mean age 54 years, 70% female). 3-T, three-dimensional (3D) T1-weighted MRI and gradient echo BOLD fMRI. To assess test-retest reliability of BOLD parameters, i.e. BOLD amplitude, time to peak, and time to baseline, BOLD fMRI scans were repeated three times immediately after each other, in both controls and mutation carriers. To assess reproducibility, BOLD fMRI scans were repeated with a 3-week interval for each subject. Linear regression analyses and two-way mixed absolute agreement intra-class correlation approach. Healthy aging was associated with decreased BOLD amplitude (β = -0.711) and prolonged time to baseline (β = 0.236) in the visual cortex after visual stimulation Reproducibility of BOLD amplitude was excellent (ICC 0.940) in the subgroup of healthy adults. Test-retest reliability for BOLD amplitude was excellent in healthy adults (ICC 0.856-0.910) and presymptomatic D-CAA mutation carriers (ICC 0.959-0.981). In symptomatic D-CAA mutation carriers, test-retest reliability was poor for all parameters (ICCs < 0.5). Healthy aging is associated with decreased cerebrovascular reactivity, measured by changes in BOLD response to visual stimulation. The BOLD amplitude appears to be a robust measurement in healthy adults and presymptomatic D-CAA mutation carriers, but not in symptomatic D-CAA mutation carriers.

Relationships between the serum TPOAb and TGAb antibody distributions and water iodine concentrations, thyroid hormones and thyroid diseases: a cross-sectional study of 2503 adults in China. The aim of this study was to explore the status of thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) in three areas with differing water iodine concentrations; and to discuss the relationships between these two thyroid antibodies and thyroid diseases in the three areas. We investigated 2503 adults from three areas. Urinary iodine concentrations, thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), TPOAb, TGAb and thyroid volume (TV) were measured, and thyroid ultrasonography was performed. The positivity rates of TGAb(+), TPOAb(+) and TGAb(+) and TPOAb(+) or TGAb(+) were significantly higher in iodine fortification (IF) areas than iodine adequate (IA) areas (all P < 0·05). In IF and iodine excess areas, the positivity rates of TPOAb(+), TGAb(+) and TPOAb(+) or TGAb(+) significantly increased with age (all P for trend < 0·05). The levels of TSH, TV and the prevalence of overt hypothyroidism, subclinical hypothyroidism and goitre were significantly elevated in the thyroid antibody-positive groups in the three areas, but the FT3 was diminished (all P < 0·010). Positivity for TPOAb and TGAb was associated with an increased risk of subclinical hypothyroidism in the three areas. In areas with different median water iodine, positivity for both TPOAb and TGAb was associated with elevated TSH values. Notably, with the increased levels of TPOAb, the frequency of abnormally elevated TSH increased dramatically in the three areas.

Symmetry-Adapted Synthesis of Dicopper Oxidases with Divergent Dioxygen Reactivity. Artificial metalloenzymes have fed our understanding of how inorganic reactivities emerge, evolve, and diversify in protein environments. Herein, we created dinuclear copper oxidases by genetically encoding a metal-ligating unnatural amino acid (bpy-Ala) per protomer in the vicinity of the innate C2 rotational axis of a homo-oligomeric protein. The inherent protein symmetry allows the precise multiplication and placement of two Cu(bpy) species. Depending on the location of bpy-Ala, the tailor-made metalloenzymes exhibited electronically uncoupled or coupled dicopper sites. Consequently, they displayed various reactivities with dioxygen associated with multiple protons and electrons, illustrating a diverse chemical repertoire of artificial copper-dependent enzymes.

Technical and economic aspects of a sequential MF + NF + zeolite system treating landfill leachate. This work explores the techno-economic aspects of landfill leachate treatment by an integrated scheme composed of microfiltration (MF), nanofiltration (NF), and zeolite application for carbon and nitrogen removal. In bench-scale experiments, MF and NF were investigated, and zeolite batch tests were carried out to determine optimum conditions. A preliminary economic analysis is presented for a 200 m3 d-1 full-scale treatment facility based on the data obtained from experimental tests and literature surveys. The maximum removals of 92%, 94%, and 79% for chemical oxygen demand (COD), absorbance at 254 nm, and ammonium nitrogen (NH4+-N) were achieved in bench experiments, respectively. It was possible to reach the local discharge standard for COD (200 mg L-1), but it was not possible to reach the Brazilian disposal requirement for NH4+-N (20 mg L-1). The total cost of the integrated MF + NF + zeolite system was estimated at 19.89 US$m-3. In this study, the costs of the zeolite application account for around 70% of the total costs of the integrated scheme. Membrane process integration was an adequate strategy for removing organic compounds at low operating costs; However, further NH4+-N depuration is needed to meet discharge requirements.

Chemical constituents from the seeds of Cullen corylifolium and their inhibitory activity on diacylglycerol acyltransferase. A large number of extracts of medicinal plants or natural products shows beneficial to combat obesity. In the present work, a new flavonoid named (2S,1″R,2″R)-4'-hydroxy-7-methoxy-6-(1,2,3-trihydroxy-3-methyl-butyl)-flavanone (1), along with seven known compounds (2-8) were isolated from the seeds of Cullen corylifolium. Their structures, including the absolute configurations, were determined by the analysis of comprehensive spectroscopic data and computational calculation methods. All isolates were evaluated for their diacylglycerol acyltransferase (DGAT) inhibitory activity. Compounds 1-4 exhibited different level of DGAT1 inhibitory activity with IC50 values ranging from 28.2 ± 1.1 to 127.3 ± 1.9 μM. In addition, 45 flavonoids which be evaluated for DGAT inhibitory activity were summarised and potential structure-activity relationships were discussed.

MRG Chip: A High-Throughput qPCR-Based Tool for Assessment of the Heavy Metal(loid) Resistome. Bacterial metal detoxification mechanisms have been well studied for centuries in pure culture systems. However, profiling metal resistance determinants at the community level is still a challenge due to the lack of comprehensive and reliable quantification tools. Here, a novel high-throughput quantitative polymerase chain reaction (HT-qPCR) chip, termed the metal resistance gene (MRG) chip, has been developed for the quantification of genes involved in the homeostasis of 9 metals. The MRG chip contains 77 newly designed degenerate primer sets and 9 published primer sets covering 56 metal resistance genes. Computational evaluation of the taxonomic coverage indicated that the MRG chip had a broad coverage matching 2 kingdoms, 29 phyla, 64 classes, 130 orders, 226 families, and 382 genera. Temperature gradient PCR and HT-qPCR verified that 57 °C was the optimal annealing temperature, with amplification efficiencies of over 94% primer sets achieving 80-110%, with R2 > 0.993. Both computational evaluation and the melting curve analysis of HT-qPCR validated a high specificity. The MRG chip has been successfully applied to characterize the distribution of diverse metal resistance determinants in natural and human-related environments, confirming its wide scope of application. Collectively, the MRG chip is a powerful and efficient high-throughput quantification tool for exploring the microbial metal resistome.

Long-term Surgical Outcomes in Patients of Centurion Syndrome: A Mystic Etiology of Epiphora in Young. To describe the clinical features and long-term outcomes of the medial canthal tendon (MCT) release procedure in patients with Centurion Syndrome (CS). We performed a retrospective analysis of the diagnosed patients with CS from July 2013 to December 2019. CS was diagnosed clinically based on the anterior displacement of MCT, anterior dislocation of lacrimal punctum out of tear lake, prominent nasal bridge, beak sign, and synophyrs. All symptomatic patients were advised the anterior limb of MCT release with modified closure of the skin incision. The outcome measures were based on Munk's score (subjective) and the fluorescein dye disappearance test (objective). A minimum postoperative follow-up of 12 months was an inclusion criterion. We studied 22 patients (44 eyes) having a median age of 14.5 years. Anteriorly displaced MCT and lacrimal punctum were noted in 44 eyes (100%), prominent nasal bridge in 20 patients (90.9%), beak sign in 36 eyes (81.8%), and synophyrs in 17 (77.3%) patients. All 44 eyes underwent MCT release with adjunctive punctoplasty (n = 6 eyes) or lower eyelid retractor plication (n = 4 eyes). At a mean follow-up of 12.6 months, 26 eyes (59.1%) showed complete response, i.e., negative FDDT and grade 0 Munk score. Partial response was noted in 14 (31.8%) eyes, i.e., delayed FDDT and reduction of ≥2 grades on Munk score. Along with the classic features of CS, beak sign and synophyrs are important diagnostic ophthalmic-facial features of CS. The transverse closure of surgical wounds may provide effective long-term benefits in the medial canthal tendon release procedure.

Isolation and structural characterization of phytoconstituents from leaves of Bignonia binata. Phytochemical investigation of Bignonia binata leaves led to the isolation of three new compounds: including a glycoside of simple alcohol, namely binatoside (2), 3,4-dihydroxy-N-methyl piperidin-2-one (7), and a phenyl ethanoid glycoside, namely bignanoside C (8), alongside with five known compounds; including a glycoside of simple alcohol; (2S) propane-1,2-diol 1-O-(6-O-caffeoy1)-β-D-glucopyranoside (1), phenyl ethanoids; leucosceptoside A (3) and plantainoside C (4), and iridoids; ipolamiide (5) and strictoloside (6). The structure of the isolated compounds was elucidated by various spectroscopic methods, including 1 D and 2 D NMR experiments, HR-ESI-MS as well as by comparison with the literature.

Metabolic Blockade-Based Genome Mining Reveals Lipochain-Linked Dihydro-β-alanine Synthetases Involved in Autucedine Biosynthesis. Continuously mining the Streptomyces olivaceus SCSIO T05 genome leads to the identification of new lipopeptides (autucedines A-C), constituting members of the 10th skeleton isolated from this strain. The corresponding biosynthetic gene cluster (aut) was verified by heterogeneous expression, and another two analogues (autucedines D and E) were isolated from the heterogeneous expression strain. Gene inactivation experiments revealed that construction of the unique "lipochain-linked dihydro-β-alanine" unit takes place prior to the NRPS assembly line.

Two-Step Kinetic Resolution of Racemic Secondary Benzylic Alcohols Using the Combination of Enantioselective Silylation and Acylation: One-Pot Procedure Catalyzed by Chiral Guanidine. A novel two-step kinetic resolution of racemic secondary benzylic alcohols with practical enantiomeric ratios was achieved. The reactions were carried out via a one-pot operation by combining enantioselective silylation and acylation mediated by the same chiral guanidine catalyst.

Etiologic mechanisms in an adapted family-based preventive intervention for underage alcohol use in Mexico: Results of an exploratory pilot study. Alcohol use represents a global health problem, especially for Latin American youth. As part of the Global Smart Drinking Goals campaign, a family-based preventive intervention was adapted and piloted in Mexico based on an existing evidence-based program, Guiding Good Choices. In this study, we explored the malleability and session-specific mean-level changes in protective and risk factors targeted by the adapted family intervention as related to the prevention of underage alcohol use and abuse. The sample consisted of 177 parents working at four private local companies who had children between the ages of 8 and 16. Data were collected before and after each program session. Linear mixed-effects models were used to examine growth trajectories and session-specific mean differences for selected etiologic factors. Significant effects on protective and risk factors were found. Among protective factors, positive family involvement showed the most considerable linear growth over time, while clear standards for youth showed the largest within-session increase. The greatest linear decrease in risk was observed for family conflict, which also showed the greatest pre-, and post-session reduction. Our findings suggest that the adapted program helped families develop protection against, and reduce risk of, alcohol use in their adolescent children. Results from this exploratory pilot study provide support for further rigorous evaluation and dissemination of the adapted intervention for Hispanic families.

Luminescent Gold Nanoclusters Interacting with Synthetic and Biological Vesicles. According to their high electron density and ultrasmall size, gold nanoclusters (AuNCs) have unique luminescence and photoelectrochemical properties that make them very attractive for various biomedical fields. These applications require a clear understanding of their interaction with biological membranes. Here we demonstrate the ability of the AuNCs as markers for lipidic bilayer structures such as synthetic liposomes and biological extracellular vesicles (EVs). The AuNCs can selectively interact with liposomes or EVs through an attractive electrostatic interaction as demonstrated by zetametry and fluorescence microscopy. According to the ratio of nanoclusters to vesicles, the lipidic membranes can be fluorescently labeled without altering their thickness until charge reversion, the AuNCs being located at the level of the phosphate headgroups. In presence of an excess of AuNCs, the vesicles tend to adhere and aggregate. The strong adsorption of AuNCs results in the formation of a lamellar phase as demonstrated by cryo-transmission electron microscopy and small-angle X-ray scattering techniques.

Bell's palsy with facial bone involvement: A rare presentation of chronic nonbacterial osteomyelitis with literature review. Chronic nonbacterial osteomyelitis (CNO) is a chronic, sterile, inflammatory disease. It primarily presents with nonspecific bone pain and swelling but ultimately can cause bone destruction and deformities, if left untreated. The involvement of the cranial bones (apart from the mandible) is rare in CNO. In this report, we present a rare case of CNO affecting facial and cranial bones presenting as facial palsy with a review of the literature about similar affection. A 10-year-old, previously healthy female was initially evaluated for swelling of the left side of her face with slight tenderness on palpation, but no fever. Her complete blood count was unremarkable, her inflammatory markers were elevated (C-reactive protein 7.5 mg/dl and erythrocyte sedimentation rate 104 mm/h), and CT of facial and skull bones and MRI of brain showed a destructive osseous process involving the left maxillary, zygomatic, sphenoid bones and the clivus. Bone biopsy of the left maxilla showed fibrous dysplasia with abscess formation, most consistent with an infectious aetiology (acute osteomyelitis). She was started on oral clindamycin for a 3-month course. The facial swelling improved after starting clindamycin, but on her sixth week of treatment, she developed right-sided Bell's palsy. An MRI of the brain showed hyperenhancement of the right seventh cranial nerve. A month later, she was evaluated for right wrist and knee swelling, pain, and limitation of movement. Skeletal survey and MRI showed multifocal lesions with mixed sclerosis and lucency. Her inflammatory markers continued to be elevated. Another bone biopsy of the right radius showed similar findings of destruction with no evidence of malignancy. She was ultimately diagnosed with CNO. She was started on nonsteroidal anti-inflammatory drugs with gastric protection and regular follow-up. Over more than a year of follow-up, the patient's inflammatory markers remain normal, and joint swelling/limitation has remained in remission. We found five additional cases in the literature that presented with a similar presentation. To our knowledge, our patient is the first reported case in the USA involving the cranial/facial bones apart from the mandible presenting with facial palsy. The affection of the facial bones (apart from the mandible) in CNO is very rare, but the awareness of such a presentation by the clinician is an important aspect of reaching the diagnosis.

Rapid Construction of Enantioenriched Benzofurochromanes by SaBOX/Copper(II) Catalyzed Enantioselective [3 + 2] Annulation of γ-Chromenes with Quinones. A rapid construction of enantioenriched benzofurochromanes was developed by SaBOX/copper(II) catalyzed enantioselective [3 + 2] annulation of γ-chromenes with quinones. This process takes advantage of the simple starting materials and a highly efficient chiral SaBOX/copper(II) catalyst system, leading to a variety of benzofurochromanes in up to 96% yield with up to 97% ee.

Whole exome sequencing and transcript analysis discover a novel pathogenic splice site mutation in DCAF17 gene underlying Woodhouse-Sakati syndrome. Woodhouse-Sakati syndrome (WSS) is an extremely rare multisystemic disorder with neuroendocrine dysfunctions. It is characterized by hypogonadism, alopecia, diabetes mellitus, intellectual disability and progressive extrapyramidal syndrome along with radiological features of small pituitary gland, progressive frontoparietal white matter changes and abnormal accumulation of iron on globus pallidus. WSS is caused by mutations in DCAF17 gene that encodes for DDB1 and CUL4 associated factor 17. In this study, we report a 17-year-old boy with clinical and radiological features of WSS including mild global developmental delay, mild intellectual disability, sensorineural hearing loss, progressive extrapyramidal syndrome, alopecia, hypogonadotropic hypogonadism and dysmorphic features. Whole exome sequencing analysis revealed a novel potentially pathogenic splice donor site variant (c.458+1G>T) on the intron 4 of DCAF17 gene. Transcript analysis revealed splicing ablation resulting in aberrant splicing of exons 3 and 5 and skipping of exon 4 (c.322_458del). This results in a frameshift and is predicted to cause premature termination of protein synthesis resulting in a protein product of length 120 amino acids (p.[Gly108Ilefs*14]). Our study identified a novel pathogenic variant causing WSS in a patient and expands the spectrum of clinical and genetic characteristics of patients with WSS.

Convenient Diaryl Ureas as Promising Anti-pseudo-allergic Agents. Allergic diseases are a group of allergen-induced unfavorable immune responses initiating various symptoms in different organs. Mas-related G protein-coupled receptor X2 (MRGPRX2) on mast cells has been reported to be responsible for immunoglobulin E (IgE)-independent immune diseases and allergic drug reactions and has therefore been a crucial drug target for the development of anti-pseudo-allergic agents. Considering the active structural features of MRGPRX2, we designed and synthesized a series of diaryl ureas (DPUs). DPUs exert promising potency for inhibiting β-hexosaminidase release in LAD2 cells with half-maximal inhibitory concentrations (IC50) values of 2.51-0.62 μM, as well as favorable antilocal and systemic anaphylaxis in mice at a dosage of 10 mg/kg. MRGPRX2 is further revealed to participate in the anti-pseudo-allergic activity of DPUs by binding with electrophilic urea and trifluoromethyl substituents. In brief, these results highlight entities with powerful electrophilic substituents as a prospective therapeutic strategy for the treatment of IgE-independent disorders.

Analysis of STMN2 CA repeats in italian ALS patients shows no association. Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease caused by a complex interaction of genetic and environmental factors. Recently, a polymorphic intronic CA repeat in STMN2 gene has been proposed as risk factor for ALS. The presence of long/long CA genotype, especially if one allele had 24 CA, was reported to be significantly associated with the disease in a cohort of sporadic ALS patients. We tested an Italian cohort of 366 ALS patients and 353 healthy controls and we found no association between CA length and ALS risk.

Evaluation of the dual effects of antiviral drugs on SARS-CoV-2 receptors and the ACE2 receptor using structure-based virtual screening and molecular dynamics simulation. The use of US FDA-approved drugs is preferred due to the need for lower costs and less time. In in silico medicine, repurposing is a quick and accurate way to screen US FDA-approved medications to find a therapeutic option for COVID-19 infection. Dual inhibitors possess dual inhibitory activity, which may be due to the inhibition of two different enzymes, and are considered better than combination therapy from the developmental and clinical perspectives. In this study, a molecular docking simulation was performed to identify the interactions of antiviral drugs with the critical residues in the binding site of the main SARS-CoV-2 protease, spike glycoprotein, and papain-like protease receptors compared to the angiotensin-converting enzyme-related carboxypeptidase (ACE2) receptor of host cells. Each of the receptors was docked with 70 US FDA-approved antiviral drugs using AutoDock Vina. A molecular dynamics (MD) simulation study was also used for 100 ns to confirm the stability behaviour of the ligand receptor complexes. Among the drugs that had the strongest interaction with the SARS-CoV-2 main protease, spike glycoprotein and papain-like protease receptors, and host cell ACE2 receptors, Simeprevir, Maraviroc and Saquinavir had dual inhibitory effects. The MD simulation study confirmed the stability of the strongest interactions between the antiviral drugs and the main protease, ACE2, spike glycoprotein, and papain-like protease receptors to 100 ns. However the results of MMPBSA analysis showed that the bond between Saquinavir and the ACE2 receptor was weak. Simeprevir and Maraviroc drugs had acceptable binding energies with dual receptors, especially the Simeprevir.Communicated by Ramaswamy H. Sarma.

Influence of firing temperature and duration on the hardness of dental zirconia for optimum selection of sintering conditions. In order to optimize the properties of dental zirconia, the sintering process involves firing zirconia to elevated temperatures for an extended time that can take several hours. The aim of this study is to investigate the effect of firing temperature and firing duration on the hardness of dental zirconia to indicate the optimum sintering conditions. Thirty-six zirconia specimens in shape of bars were randomly assigned to nine groups. The zirconia specimen groups were sintered using a sintering furnace with different firing temperatures (900°C, 1200°C, and 1800°C) and firing durations (6, 9, and 12 h). A total of 108 hardness measurements were conducted for all specimens (12 hardness readings per group). For each of the specimen groups, micro Vickers hardness test was performed using a load of 1 Kgf (9.807 N) and the Vickers hardness number was computed. Statistical analysis using Kruskal-Wallis test was conducted to examine the significant differences on Vickers hardness number HV among the specimen groups according to the firing parameters with 0.005 p-value used as an indicator. Results suggest that there is an association between the increase in the hardness number and the increase in firing duration at a given firing temperature. The results also indicate that there is an association between the increase in the hardness number and increase in firing temperature at a given firing duration. The greatest rate of hardness increase with time is associated with groups of firing temperature 1200°C. The highest rate of hardness increase with temperature happened during the first 6 h of sintering process. On the other hand, there is no significant increase in the hardness number when increasing the firing temperature beyond 1200°C.

Efficient drug development of oseltamivir capsules based on process control, bioequivalence and PBPK modeling. Oseltamivir phosphate is used to treat influenza. For registration of a generic product, bioequivalence studies are crucial, however, in vitro studies can sometimes replace the conventional human pharmacokinetic. To assess whether the dissolution profile is comparable with the in vivo release, physiologically based pharmacokinetic absorption models (PBPK) are being used. The aim of the study was to develop a generic capsule of oseltamivir phosphate 30 mg with process understanding and control, development of PBPK model and comparison of virtual bioequivalence study (VBE) to the real bioequivalence study that was also performed. For that, 30 mg capsules were prepared by wet granulation according to 22 full factorial design. The biobatch was prepared with the selected process and a batch was made with the API from the second manufacture. Both manufactures presented polymorph A and the second manufacture showed higher particle size. Product batches produced without adding water during granulation showed higher dissolution. The addition of water associated with higher conical mill speed, lowered the average weight of the capsules. The biobatch dissolution was similar to Tamiflu; also, they were bioequivalent. The crossover VBE between the biobatch and Tamiflu corroborated with the real bioequivalence study. The same result was found for the batch with higher particle size. PBPK model showed that computer simulations can help pharmaceutical companies to replace in vivo studies.

Measuring disability in amyotrophic lateral sclerosis/motor neuron disease: the WHODAS 2.0-36, WHODAS 2.0-32, and WHODAS 2.0-12. Aim: To investigate whether the World Health Organization Disability Assessment Schedule 2.0 (WHODAS) can provide interval level measurement of disability in Amyotrophic Lateral Sclerosis (ALS), allowing parametric analyses. Methods: Data on the WHODAS 12, 32, and 36-item versions, from 1120 patients studied at one or more time points, were fit to the Rasch model and comparisons made against ALSFRS-R, King's staging, and mortality. Trajectory modeling was undertaken for a newly diagnosed (≤6 months) cohort of 454 individuals. Results: Total scores for WHODAS 32 and 36-item versions can be converted to interval level measurement suitable for individual clinical use, and the 12-item WHODAS total for group use. The 36-item version is shown to be equivalent to the 32-item version. Expected correlations were seen with King's staging, ALSFRS-R, and EQ-5D-5L. Trajectory analysis of disability (WHODAS 2.0) showed three clearly demarcated groups with differences in King's staging, depressive symptomatology and mortality, but not age. Conclusions: The WHODAS 2.0 is a brief patient reported outcome measure which can be used to measure disability in ALS. Provided the patient answers all 36 (32 if not working) items, the conversion table produces an interval level estimate for parametric analyses. The different trajectories demonstrated from diagnosis support the concept of a prodromal period, and suggest the WHODAS 2.0 could be used for surveillance of at risk populations, such as those with genetic predisposition.