Miracle-dz/UniFAR-FTUs huggingface dataset:
The efficacy and safety of cyclosporine A plus androgen versus androgen alone for adult patients with non-severe aplastic anemia in China: a meta-analysis of randomized controlled trials

ABSTRACT Background Whether combined CsA with androgen therapy was superior to androgen therapy alone in NSAA remains controversial. This study aimed to assess the efficacy and safety of combined therapy versus androgen therapy for NSAA patients using a meta-analytic approach. Methods An electronic database of PubMed, EmBase, Cochrane library, CNKI, VIP, and Wanfang was systematically searched for randomized controlled trials (RCTs) from their inception to February 2020. The primary endpoint was effective rate, while the secondary endpoints included white blood cell (WBC), hemoglobin, platelet, and potential adverse events. The pooled results from included trials were calculated with the random-effects model. Results Forty-three RCTs recruited 2610 NSAA patients for the final quantitative meta-analysis. We noted that combined therapy was associated with an increased incidence of effective rate than androgen therapy alone (relative risk [RR]: 1.35; 95% confidence interval [CI]: 1.29–1.41; P < 0.001). Moreover, patients treated with combined therapy were associated with higher WBC (weighted mean difference [WMD]: 1.22; 95%CI: 0.94–1.49; P < 0.001), hemoglobin (WMD: 12.93; 95%CI: 8.86–17.01; P < 0.001), and platelet (WMD: 8.65; 95%CI: 7.05–10.24; P < 0.001). Finally, the pooled incidence of hirsutism, handshake, gingiva hyperplasia, liver function damage, and renal function damage were 0.35 (95%CI: 0.22–0.48), 0.24 (95%CI: 0.15–0.32), 0.22 (95%CI: 0.10–0.35), 0.19 (95%CI: 0.14–0.25), and 0.06 (95%CI: 0.01–0.11), respectively. Conclusions This study found that combined CsA with androgen therapy was superior to androgen therapy alone for Chinese patients with NSAA, and the most common adverse of combined therapy included hirsutism, handshake, gingiva hyperplasia, liver function damage, and renal function damage.
Alloy-type Anodes for High-performance Rechargeable Batteries.

Alloy-type anodes are one of the most promising classes of next-generation anode materials due to their ultra-high theoretical capacity (2~10 times that of graphite). However, current alloy-type anodes have several limitations: a huge volume expansion, a high tendency to fracture and disintegrate, an unstable solid-electrolyte interphase (SEI) layer, and low Coulombic efficiency. Efforts to overcome these challenges are ongoing. This review details recent progress in the research of batteries based on alloy-type anodes and discusses the direction of their future development. We conclude that improvements in structural design, the introduction of a protective interface, and the selection of suitable electrolytes are the most effective ways to improve the performance of alloy-type anodes. Furthermore, future studies should direct more attention toward analyzing their synergistic promoting effect.
Efficient engineering of human auricular cartilage through mesenchymal stem cell chaperoning

A major challenge to the clinical translation of tissue‐engineered ear scaffolds for ear reconstruction is the limited auricular chondrocyte (hAuC) yield available from patients. Starting with a relatively small number of chondrocytes in culture results in dedifferentiation and loss of phenotype with subsequent expansion. To significantly decrease the number of chondrocytes required for human elastic cartilage engineering, we co‐cultured human mesenchymal stem cells (hMSCs) with HAuCs to promote healthy elastic cartilage formation. HAuCs along with human bone marrow‐derived hMSCs were encapsulated into 1% Type I collagen at 25 million/mL total cell density with different ratios (HAuCs/hMSCs: 10/90, 25/75, 50/50) and then injected into customized 3D‐printed polylactic acid (PLA) ridged external scaffolds, which simulate the shape of the auricular helical rim, and implanted subcutaneously in nude rats for 1, 3 and 6 months. The explanted constructs demonstrated near complete volume preservation and topography maintenance of the ridged “helical” feature after 6 months with all ratios. Cartilaginous appearing tissue formed within scaffolds by 3 months, verified by histologic analysis demonstrating mature elastic cartilage within the constructs with chondrocytes seen in lacunae within a Type II collagen and proteoglycan‐enriched matrix, and surrounded by a neoperichondrial external layer. Compressive mechanical properties comparable to human elastic cartilage were achieved after 6 months. Co‐implantation of hAuCs and hMSCs in collagen within an external scaffold efficiently produced shaped human elastic cartilage without volume loss even when hAuC comprised only 10% of the implanted cell population, marking a crucial step toward the clinical translation of auricular tissue engineering.
Diatom community composition on submerged macrophyte species from an Ontario (Canada) lake

The introduction of invasive macrophyte species can affect submerged macrophyte community composition and abundance, which in turn can alter the functions of lake ecosystems. Knowing when and how invasive macrophytes arrive and spread can help disentangle the effects of invasive species from other stressors on lake ecosystems. This requires a long‐term (decades) perspective of macrophyte community composition, which is rarely available. An alternative is paleolimnological inferences of macrophyte community composition from fossil diatom assemblages, which requires knowledge of epiphytic diatom communities. Here, we investigated the epiphytic diatom community composition of three common submerged macrophyte species (Chara sp., Potamogeton robbinsii, and the invasive Myriophyllum spicatum) in a typical temperate, mixed forest lake, Chandos Lake, Ontario, Canada, to provide a basis for future paleolimnological research. Non‐parametric, multivariate analysis of variance indicated a statistically significant difference in the epiphytic diatom communities of different macrophyte species, despite principal components analysis showing some overlap among the diatom communities. Diatom community composition of all macrophytes had abundant Achnanthidium minutissimum and Cocconeis placentula. Generalized linear models and univariate analysis of variance identified six diatoms (Encyonopsis microcephala, Epithemia turgida, Gomphonema parvulius, Navicula gerloffi, Rhopalodia gibba, and Rossithidium anastasiae) that were significantly different among macrophyte species. Although it remains uncertain whether these differences are sufficient to infer historical macrophyte community composition from epiphytic diatom fossil assemblages, our results indicate the potential of such an approach and offer suggestions for future research.
Reliability of the footwear total asymmetry score tool

Abstract Both design and degradation of footwear contribute to mediolateral asymmetry of the inner-, mid- and outersole. Mediolateral asymmetry in footwear affects joint moments around the ankle, knee and hip and may contribute to lower limb injuries and the development of knee osteoarthritis. The aim of this study was to establish the reliability of an objective clinical assessment tool for measuring footwear asymmetry. We assessed the within-rater, between-rater and between-day reliability of the Footwear Total Mediolateral Asymmetry Score tool. Two novice and two expert raters assessed ten individual shoes varying in style, size and brand. The inner-, mid- and outersole thickness of each shoe was measured at 14 locations, while midsole hardness was assessed at four locations. Within-rater ICC(2,1), between-rater ICC(2,1),(2,2),(2,3) and between-day ICC(2,1),(2,2),(2,3) intraclass correlation coefficients were calculated for each measurement and for the total asymmetry scores of each shoe. Standard error of measurements (SEM) was determined for all footwear measurements and minimal detectable differences (MDD) were determined for between-day measurements. Within- and between-rater and between-day reliability of all measurements were poor to excellent (0.31–1.00). The MDD for rearfoot and forefoot total asymmetry scores was ≤1 mm, regardless of rater experience. Based on our findings, the footwear total asymmetry score tool is reliable for assessing the location and magnitude of mediolateral asymmetry in running shoes.
Microphysiological Systems Evaluation: Experience of TEX-VAL Tissue Chip Testing Consortium.

Much has been written and said about the promise and excitement of microphysiological systems, miniature devices that aim to recreate aspects of human physiology on a chip. The rapid explosion of the offerings and persistent publicity placed high expectations on both product manufacturers and regulatory agencies to adopt the data. Inevitably, discussions of where this technology fits in chemical testing paradigms are ongoing. Some end-users became early adopters, while others have taken a more cautious approach because of the high cost and uncertainties of their utility. Here, we detail the experience of a public-private collaboration established for testing of diverse microphysiological systems. Collectively, we present a number of considerations on practical aspects of using microphysiological systems in the context of their applications in decision-making. Specifically, future end-users need to be prepared for extensive on-site optimization and have access to a wide range of imaging and other equipment. We reason that cells, related reagents and the technical skills of the research staff, not the devices themselves, are the most critical determinants of success. Extrapolation from concentration-response effects in microphysiological systems to human blood or oral exposures, difficulties with replicating the whole organ, and long-term functionality remain as critical challenges. Overall, we conclude that it is unlikely that a rodent- or human-equivalent model is achievable through a finite number of microphysiological systems in the near future; therefore, building consensus and promoting the gradual incorporation of these models into tiered approaches for safety assessment and decision-making is the sensible path to wide adoption.
Understanding Customer Opinions From Online Discussion Forums: A Design Science Framework

Abstract Online discussion forums, which are full of user-generated content including user opinions and comments, are a potential gold mine for exploring new and useful ideas to augment competence in innovation. Companies need to systematically analyze and interpret online commentaries to enhance in-house research and design activities. To this end, a framework is proposed using a design science approach to enable automatic analysis of the content of online opinions and comments in connection with specific products, using a web lexicon established for this purpose. Furthermore, this framework is applied to an automobile as a proof-of-concept. Several nicknames for the car brand studied were created by web users, some with irony and sarcasm. A few metaphorical expressions were also used to describe product features. Engineering practitioners should recognize the importance of stylized online expressions in order to have a better understanding of customer needs and expectations through the application of this framework, which incorporates an evolutionary web lexicon.
Somatostatin receptor ligands suppressed proliferation and lipogenesis in 3T3‐L1 preadipocytes

Somatostatin and its analogues, known as somatostatin receptor ligands (SRLs), have been reported to attenuate weight gain in some clinical settings. However, their direct effects on preadipocytes are barely investigated. Therefore, this study aimed to evaluate the influence of SRLs on preadipocytes and to further explore the potential mechanisms. Cell Counting Kit‐8 assay, Oil Red O staining, triglyceride contents measurements, quantitative polymerase chain reaction (qPCR) and western blot were used to investigate the effects of SRLs on preadipocytes. We found that three SRLs (octreotide, TT232 and pasireotide) inhibited cell viability after 8–48 h but not 4 h. Further western blot results showed that they significantly suppressed activation of PI3K/Akt pathway. Besides, lipid accumulation was also significantly inhibited by these SRLs. Moreover, mRNA levels of some critical adipogenic markers, including Pparg, Cebpa, Fasn, Fabp4, Acaca and Lpl, were downregulated by the treatments of all these SRLs. Consistently, the protein expression of peroxisome proliferator‐activated receptor γ (PPARγ), CCAAT/enhancer binding protein α (C/EBPα) and fatty acid synthase (FAS) was also suppressed by SRLs. SRLs inhibit the proliferation and lipogenesis in preadipocytes. Their inhibitory effects on cell proliferation may be mediated by the downregulated PI3K/Akt pathway, and the suppressive actions on lipogenesis may be related to the decreased PPARγ and C/EBPα expression.
Nafamostat is a Potent Human Diamine Oxidase Inhibitor Possibly Augmenting Hypersensitivity Reactions during Nafamostat Administration

Nafamostat is an approved short-acting serine protease inhibitor. However, its administration is also associated with anaphylactic reactions. One mechanism to augment hypersensitivity reactions could be inhibition of diamine oxidase (DAO). The chemical structure of nafamostat is related to the potent DAO inhibitors pentamidine and diminazene. Therefore, we tested whether nafamostat is a human DAO inhibitor. Using different activity assays, nafamostat reversibly inhibited recombinant human DAO with an IC50 of 300–400 nM using 200 µM substrate concentrations. The Ki of nafamostat for the inhibition of putrescine and histamine deamination is 27 nM and 138 nM, respectively For both substrates, nafamostat is a mixed mode inhibitor with P values of <0.01 compared with other inhibition types. Using 80–90% EDTA plasma, the IC50 of nafamostat inhibition was approximately 360 nM using 20 µM cadaverine. In 90% EDTA plasma, the IC50 concentrations were 2–3 µM using 0.9 µM and 0.18 µM histamine as substrate. In silico modeling showed a high overlap compared with published diminazene crystallography data, with a preferred orientation of the guanidine group toward topaquinone. In conclusion, nafamostat is a potent human DAO inhibitor and might increase severity of anaphylactic reaction by interfering with DAO-mediated extracellular histamine degradation. SIGNIFICANCE STATEMENT Treatment with the short-acting anticoagulant nafamostat during hemodialysis, leukocytapheresis, extracorporeal membrane oxygenator procedures, and disseminated intravascular coagulation is associated with severe anaphylaxis in humans. Histamine is a central mediator in anaphylaxis. Potent inhibition of the only extracellularly histamine-degrading enzyme diamine oxidase could augment anaphylaxis reactions during nafamostat treatment.
Processes and mechanisms of coastal woody‐plant mortality

Observations of woody plant mortality in coastal ecosystems are globally widespread, but the overarching processes and underlying mechanisms are poorly understood. This knowledge deficiency, combined with rapidly changing water levels, storm surges, atmospheric CO2, and vapor pressure deficit, creates large predictive uncertainty regarding how coastal ecosystems will respond to global change. Here, we synthesize the literature on the mechanisms that underlie coastal woody‐plant mortality, with the goal of producing a testable hypothesis framework. The key emergent mechanisms underlying mortality include hypoxic, osmotic, and ionic‐driven reductions in whole‐plant hydraulic conductance and photosynthesis that ultimately drive the coupled processes of hydraulic failure and carbon starvation. The relative importance of these processes in driving mortality, their order of progression, and their degree of coupling depends on the characteristics of the anomalous water exposure, on topographic effects, and on taxa‐specific variation in traits and trait acclimation. Greater inundation exposure could accelerate mortality globally; however, the interaction of changing inundation exposure with elevated CO2, drought, and rising vapor pressure deficit could influence mortality likelihood. Models of coastal forests that incorporate the frequency and duration of inundation, the role of climatic drivers, and the processes of hydraulic failure and carbon starvation can yield improved estimates of inundation‐induced woody‐plant mortality.
Contrasting the Social Cognitive and Metacognitive Capacities Among Patients With Schizophrenia and Autism Spectrum Disorders Enrolled in Psychiatric Rehabilitation

Abstract Unique deficits in synthetic metacognition have been found in schizophrenia when compared with other psychiatric conditions and community controls. Although persons with autism spectrum disorders (ASD) display similar deficits in social cognition relative to those with schizophrenia, to date no study has compared metacognitive function between these groups. We aimed to compare the metacognitive capacities of persons with schizophrenia and ASD and their associations with other outcomes (neurocognition, social cognition, depression, and quality of life). Fifty-six outpatients with schizophrenia or ASD (mean age, 32.50 [9.05]; 67.9% male) were recruited from two French Centers of Reference for Psychiatric Rehabilitation of the REHABase cohort. Evaluation included the Indiana Psychiatric Illness Interview, Metacognition Assessment Scale–Abbreviated, Movie for the Assessment of Social Cognition, and a large cognitive battery. Compared with those with schizophrenia, participants with ASD had higher self-reflectivity (p = 0.025; odds ratio, 1.38 [1.05–1.86]) in univariable analyses. Metacognitive deficits may be found in ASD with a profile that varies from what is found in schizophrenia. It is possible that methods for enhancing metacognitive abilities during psychiatric rehabilitation may be refined to assist adults with ASD to better manage their own recovery.
Effectiveness and safety of isavuconazole prophylaxis for invasive fungal infections in the haematologic setting

ABSTRACT Objectives Patients with haematologic malignancies are at high risk of developing invasive fungal infections (IFIs). Current guidelines recommend the use of azoles for IFI prophylaxis; however, in many clinical situations, antifungal prophylaxis is used off-label. We conducted a systematic literature review to provide haematologists with the available evidence on the effectiveness and safety of isavuconazole in IFI prophylaxis in interventional and real-world, observational studies. Methods Embase, MEDLINE and Cochrane Library databases, and relevant conference proceedings and clinical trial registries, were searched for studies on the effectiveness and safety of isavuconazole prophylaxis in adults at high risk of IFIs. Studies were assessed for inclusion and risk of bias. Results Nine studies were eligible for inclusion in the review, eight of which were in haematologic populations (patients undergoing haematopoietic stem cell transplantation or with acute myeloid leukaemia or myelodysplastic syndromes; n = 5) or included haematologic populations (n = 3). Evidence from these studies suggests isavuconazole is effective for IFI prophylaxis in the haematologic setting. However, the studies frequently lacked safety data, most were based on small patient populations from single centres and risk of bias could not be assessed for five studies. Discussion These findings provide evidence for isavuconazole as an alternative azole for prophylaxis in high-risk populations. Limitations include lack of applicability of risk of bias assessment tools, level of filtering applied in the search strategy and focus on English-language publications. Conclusion Isavuconazole may be an effective azole for IFI prophylaxis in high-risk haematologic populations, although further studies are needed.
Noncanonical NF-κB factor p100/p52 regulates homologous recombination and modulates sensitivity to DNA-damaging therapy

Abstract Homologous recombination (HR) serves multiple roles in DNA repair that are essential for maintaining genomic stability, including double-strand DNA break (DSB) repair. The central HR protein, RAD51, is frequently overexpressed in human malignancies, thereby elevating HR proficiency and promoting resistance to DNA-damaging therapies. Here, we find that the non-canonical NF-κB factors p100/52, but not RelB, control the expression of RAD51 in various human cancer subtypes. While p100/p52 depletion inhibits HR function in human tumor cells, it does not significantly influence the proficiency of non-homologous end joining, the other key mechanism of DSB repair. Clonogenic survival assays were performed using a pair DLD-1 cell lines that differ only in their expression of the key HR protein BRCA2. Targeted silencing of p100/p52 sensitizes the HR-competent cells to camptothecin, while sensitization is absent in HR-deficient control cells. These results suggest that p100/p52-dependent signaling specifically controls HR activity in cancer cells. Since non-canonical NF-κB signaling is known to be activated after various forms of genomic crisis, compensatory HR upregulation may represent a natural consequence of DNA damage. We propose that p100/p52-dependent signaling represents a promising oncologic target in combination with DNA-damaging treatments.
Regression Discontinuity for Binary Response and Local Maximum Likelihood Estimator to Extrapolate Treatment

Regression discontinuity is popular in finding treatment/policy effects when the treatment is determined by a continuous variable crossing a cutoff. Typically, a local linear regression (LLR) estimator is used to find the effects. For binary response, however, LLR is not suitable in extrapolating the treatment, as in doubling/tripling the treatment dose/intensity. The reason is that doubling/tripling the LLR estimate can give a number out of the bound [ − 1 , 1 ] , despite that the effect should be a change in probability. We propose local maximum likelihood estimators which overcome these shortcomings, while giving almost the same estimates as the LLR estimator does for the original treatment. A simulation study and an empirical analysis for effects of an income subsidy program on religion demonstrate these points.
Psychological Stress Management and Stress Reduction Strategies for Stroke Survivors: A Scoping Review

Abstract Background Stroke can be a life-changing event, with survivors frequently experiencing some level of disability, reduced independence, and an abrupt lifestyle change. Not surprisingly, many stroke survivors report elevated levels of stress during the recovery process, which has been associated with worse outcomes. Purpose Given the multiple roles of stress in the etiology of stroke recovery outcomes, we aimed to scope the existing literature on stress management interventions that have been trialed in stroke survivors. Methods We performed a database search for intervention studies conducted in stroke survivors which reported the effects on stress, resilience, or coping outcome. Medline (OVID), Embase (OVID), CINAHL (EBSCO), Cochrane Library, and PsycInfo (OVID) were searched from database inception until March 11, 2019, and updated on September 1, 2020. Results Twenty-four studies met the inclusion criteria. There was significant variation in the range of trialed interventions, as well as the outcome measures used to assess stress. Overall, just over half (13/24) of the included studies reported a benefit in terms of stress reduction. Acceptability and feasibility were considered in 71% (17/24) and costs were considered in 17% (4/24) of studies. The management of stress was rarely linked to the prevention of symptoms of stress-related disorders. The overall evidence base of included studies is weak. However, an increase in the number of studies over time suggests a growing interest in this subject. Conclusions Further research is required to identify optimum stress management interventions in stroke survivors, including whether the management of stress can ameliorate the negative impacts of stress on health.