bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinically actionable genotypes for anticancer prescribing among >1500 patients with pharmacogenomic testing
Authors: Reizine Natalie M. , Danahey Keith , Truong Tien M. , George David , House Larry K. , Karrison Theodore G. , van Wijk Xander M. R. , Yeo Kiang‐Teck J. , Ratain Mark J. , O’Donnell Peter H.
Published: January 2022

BACKGROUND

In recent years, there has been increasing evidence supporting the role of germline pharmacogenomic factors predicting toxicity for anticancer therapies. Although somatic genomic data are used frequently in oncology care planning, germline pharmacogenomic testing is not. This study hypothesizes that comprehensive germline pharmacogenomic profiling could have high relevance for cancer care.

METHODS

Between January 2011 and August 2020, patients at the University of Chicago Medical Center were genotyped across custom germline pharmacogenomic panels for reasons unrelated to cancer care. Actionable anticancer pharmacogenomic gene/drug interactions identified by the FDA were defined including:CYP2C9(erdafitinib),CYP2D6(gefitinib),DPYD(5‐fluorouracil and capecitabine),TPMT(thioguanine and mercaptopurine), andUGT1A1(belinostat, irinotecan, nilotinib, pazopanib, and sacituzumab‐govitecan hziy). The primary objective was to determine the frequency of individuals with actionable or high‐risk genotypes across these 5 key pharmacogenes, thus potentially impacting prescribing for at least 1 of these 11 commonly prescribed anticancer therapies.

RESULTS

Data from a total of 1586 genotyped individuals were analyzed. The oncology pharmacogene with the highest prevalence of high‐risk, actionable genotypes wasUGT1A1, impacting 17% of genotyped individuals. ActionableTPMTandDPYDgenotypes were found in 9% and 4% of patients, respectively. Overall, nearly one‐third of patients genotyped across all 5 genes (161/525, 31%) had at least one actionable genotype.

CONCLUSIONS

These data suggest that germline pharmacogenomic testing for 5 key pharmacogenes could identify a substantial proportion of patients at risk with standard dosing, an estimated impact similar to that of somatic genomic profiling.

LAY SUMMARY

Differences in our genes may explain why some drugs work safely in certain individuals but can cause side effects in others.

Pharmacogenomics is the study of how genetic variations affect an individual's response to medications.

In this study, an evaluation was done for important genetic variations that can affect the tolerability of anticancer therapy.

By analyzing the genetic results of >1500 patients, it was found that nearly one‐third have genetic variations that could alter recommendations of what drug, or how much of, an anticancer therapy they should be given.

Performing pharmacogenomic testing before prescribing could help to guide personalized oncology care.
Identification of tissue optical properties during thermal laser‐tissue interactions: An ensemble Kalman filter‐based approach
Authors: Arnold Andrea , Fichera Loris
Published: January 2022

In this article, we propose a computational framework to estimate the physical properties that govern the thermal response of laser‐irradiated tissue. We focus in particular on two quantities, the absorption and scattering coefficients, which describe the optical absorption of light in the tissue and whose knowledge is vital to correctly plan medical laser treatments. To perform the estimation, we utilize an implementation of the ensemble Kalman filter (EnKF), a type of Bayesian filtering algorithm for data assimilation. Unlike prior approaches, in this work, we estimate the tissue optical properties based on observations of the tissue thermal response to laser irradiation. This method has the potential for straightforward implementation in a clinical setup, as it would only require a simple thermal sensor, for example, a miniaturized infrared camera. Because the optical properties of tissue can undergo shifts during laser exposure, we employ a variant of EnKF capable of tracking time‐varying parameters. Through simulated experimental studies, we demonstrate the ability of the proposed technique to identify the tissue optical properties and track their dynamic changes during laser exposure, while simultaneously tracking changes in the tissue temperature at locations beneath the surface. We further demonstrate the framework's capability in estimating additional unknown tissue properties (i.e., the volumetric heat capacity and thermal conductivity) along with the optical properties of interest.
Design of Ni‐substituted La2(CeZrNi)2O7 Pyrochlore Catalysts for Methane Dry Reforming
Authors: Bai Jieru , Fu Yu , Kong Wenbo , Pan Bingrong , Yuan Changkun , Li Shuqing , Wang Jiyang , Zhang Jun , Sun Yuhan
Published: January 2022

Ni‐based catalysts for dry reforming of methane (DRM) are prone to suffer from deactivation caused by carbon deposition and sintering. Pyrochlore (typically A2B2O7) is a thermostable material with substantial redox capacity, which makes it suitable as a support for Ni‐based DRM catalysts. Here we demonstrated that by adjusting the Zr/Ce ratio in the B‐site of the La2(CeZrNi)2O7 (10 wt.% Ni loading), its structural order could be significantly altered. With decreasing Zr/Ce ratio, the structure of the catalysts became less ordered with a phase transformation from pyrochlore (La2Zr2O7) to defective fluorite (La2Ce2O7). Meanwhile, a second phase La2NiZrO6/LaNiO3 other than pyrochlore was formed for each sample. By tuning the structure, samples presented different properties and XPS results illustrated that the compositions of the surface oxygen species of samples were significantly different. Catalysts possessing more oxygen vacancies displayed evidently enhanced coke resistance. Among all five catalysts, LNZ3C1 exhibited the highest activity, stability and carbon deposition resistance, which could be attributed to the most oxygen vacancies, the strongest nickel‐carrier interaction, and the best particle size distribution of it.
Research on the Lattice Matching of Different Solute Atoms in BCC Fe: A Molecular Dynamics Simulation
Authors: Wu Minghui , Zhang Xiaoxun , Ma Fang , Li Jiayi , Tian Wenqi , Gongcheng Meiqi , Xu Luyang , Chang Gaoyuan , Zhang Cheng
Published: January 2022

In this article, molecular dynamics simulation is used to primarily explore the lattice matching problem of solute atoms in different configurations after entering the Fe lattice at 0 K temperature. It reveals that by changing the initial configurations, metal solute atoms (Cr, Cu, Ti, Al) are more stable in the <110> configuration while C atom tends to stay in the octahedral gap of the BCC lattice. In addition, the matching mechanisms of different solute atoms in BCC Fe lattice in different configurations are elaborated in detail. The relaxation of metal solute atoms in different configurations eventually forms different stable structures while C atoms only exist in the nearest‐neighbor octahedral gap of the BCC Fe lattice in each configuration.
The Ideal and Regular Mechanisms of Hematite Reduction Reactions
Authors: Zhang Wei , Xue Zhengliang , Zou Zongshu , Saxén Henrik
Published: January 2022

The thermodynamic data of iron oxides reduction reactions from the most recognized thermodynamic database (NIST‐JANAF) show remarkable difference between stoichiometric and nonstoichiometric iron oxides. Iron oxides reduction equilibria in both CO‐CO2 and H2‐H2O atmospheres are calculated with Dieckmann's and Weiss’ defect models. Relevant literatures are investigated and reduction experiments are carried out to complement and interpret the newly calculated equilibrium diagram. The results suggest a conjecture of two routes for hematite reduction reactions. With the ideal and widely accepted mechanism, hematite is reduced to magnetite and then to iron below 576 °C, while the reduction route follows the sequence of Fe2O3 → Fe3−δO4 → FexO → Fe above 576 °C. With the regular but always unrecognized mechanism, the reduction process of hematite experiences Fe3O4, FeO, and Fe step by step in all possible temperature above 156 °C. In the regular mechanism, sufficient scattered impurities occupy crystal interstices of magnetite and prevent the newly produced FeO unit cell from dissolving into the solid solution of magnetite, and then the FeO will accumulate above 156 °C. Actually the regular mechanism is hard to realize and usually confused with the ideal mechanism. The presence of the regular mechanism is proved by experimental phenomena of the drop of eutectoid temperature.
How does corporate R&D investment respond to climate policy uncertainty? Evidence from heavy emitter firms in the United States
Authors: Hoang Khanh
Published: January 2022

This study explores how climate policy uncertainty (CPU) affects research and development (R&D) investment of heavy emitter firms in the United States during 2000–2019. Our empirical evidence indicates that while CPU exerts a positive impact on R&D investment of general firms, it seems to be a completely different story for heavy emitter firms. After a battery of sensitivity tests, we find a robust negative impact of CPU on R&D investment of heavy emitters, suggesting that those firms play a “wait‐and‐see” strategy in response to changes in environmental policies until more is known to make decisions. However, such behavior is not observed in light emitters. Even among heavy emitters, we show that the impact of CPU is only pronounced in heavy emitters with more technology uncertainty. Further analyses show such an impact varies with management sentiment, managerial ability, and firm maturity. Our findings have implications for policymaking and corporate strategy of heavy emitters in response to CPU.
Inaccurate recognition of own comorbidities is associated with poor prognosis in elderly patients with heart failure
Authors: Maeda Daichi , Matsue Yuya , Kagiyama Nobuyuki , Jujo Kentaro , Saito Kazuya , Kamiya Kentaro , Saito Hiroshi , Ogasahara Yuki , Maekawa Emi , Konishi Masaaki , Kitai Takeshi , Iwata Kentaro , Wada Hiroshi , Hiki Masaru , Dotare Taishi , Sunayama Tsutomu , Kasai Takatoshi , Nagamatsu Hirofumi , Ozawa Tetsuya , Izawa Katsuya , Yamamoto Shuhei , Aizawa Naoki , Yonezawa Ryusuke , Oka Kazuhiro , Momomura Shin‐ichi , Minamino Tohru
Published: January 2022

Aims

A patient's understanding of his or her own comorbidities is part of the recommended patient education for those with heart failure. The accuracy of patients' understanding of their comorbidities and its prognostic impact have not been reported.

Methods and results

Patients hospitalized for heart failure (n = 1234) aged ≥65 years (mean age: 80.1 ± 7.7 years; 531 females) completed a questionnaire regarding their diagnoses of diabetes, malignancy, stroke, hypertension, chronic obstructive pulmonary disease (COPD), and coronary artery disease (CAD). The patients were categorized into three groups based on the number of agreements between self‐reported comorbidities and provider‐reported comorbidities: low (1–2, n = 19); fair (3–4, n = 376); and high (5–6, n = 839) agreement groups. The primary outcome was a composite of all‐cause mortality or heart failure rehospitalization at 1 year. The low agreement group had more comorbidities and a higher prevalence of a history of heart failure. The agreement was good for diabetes (κ = 0.73), moderate for malignancy (κ = 0.56) and stroke (κ = 0.50), and poor‐to‐fair for hypertension (κ = 0.33), COPD (κ = 0.25), and CAD (κ = 0.30). The fair and low agreement groups had poorer outcomes than the good agreement group [fair agreement group: hazard ratio (HR): 1.25; 95% confidence interval (CI): 1.01–1.56; P = 0.041; low agreement group: HR: 2.74: 95% CI: 1.40–5.35; P = 0.003].

Conclusions

The ability to recognize their own comorbidities among older patients with heart failure was low. Patients with less accurate recognition of their comorbidities may be at higher risk for a composite of all‐cause mortality or heart failure rehospitalization.
Intramolecular Displacement Reactions Involving Sulfur Leading to the Formation of 3,6‐Thiaanhydro Sugar Derivatives during the Synthesis of 3,5‐Dithio‐glucofuranose
Authors: Liao Xiaoxiao , Yuan Kai , Crich David
Published: January 2022

During a synthesis of 3,5‐dithio‐glucofuranose, we discovered two interesting intramolecular displacement reactions involving thiolate sulfur on the one hand and a thiirane sulfur on the other. Both generated 3,6‐thiaanhydro structures. We solved the intramolecular displacement problem by using a 5‐S,6‐O‐isopropylidene protecting group and accomplished 3,5‐dithio‐glucofuranose synthesis in 9 % overall yield.
Insights into the Gold‐Catalyzed Cycloisomerization of 3‐Allyl‐1,4‐diynes for the Synthesis of Bicyclic Hydrocarbons
Authors: Yu Jhen‐Kuei , Czekelius Constantin
Published: January 2022

An efficient protocol for the synthesis of 3‐ethynyl‐2‐aryl‐bicyclo[3.1.0]hexenes through a gold‐catalyzed enyne cyclization was established in this work. Depending on the specific substitution pattern, unusual cationic rearrangements of the corresponding gold carbene were revealed, leading to either cyclohexadienes or 5,9‐methanobenzo[8]annulene derivatives, respectively.
Total Synthesis and Antibiotic Properties of Amino‐Functionalized Aromatic Terpenoids Related to Erogorgiaene and the Pseudopterosins
Authors: Schumacher Christian Eric , Rausch Marvin , Greven Tobias , Neudörfl Jörg‐Martin , Schneider Tanja , Schmalz Hans‐Günther
Published: January 2022

Following a concept recently introduced by Hergenrother,[6] the present study addresses the question of whether certain antimicrobially active aromatic (marine) natural products can be converted into more potent broad‐spectrum antibiotics by introducing an aminoalkyl side chain. To this end, phenolic mono‐ and sesquiterpenoids (incl. carvacrol, xanthorrhizol, and 7‐hydroxycalamene) as well as the diterpenes 7‐hydroxyerogorgiaene and 9‐deoxypseudopterosin A were converted into amino‐functionalized analogs that display either an amino‐methyl or a 2‐amino‐ethoxy substituent in place of (or next to) the OH group. This was achieved either by Pd‐catalyzed nitromethylation/reduction of the aryltriflates, by O‐alkylation of the phenols with bromoacetonitrile and subsequent reduction, or by ortho‐hydroxymethylation/amination. During the study, an efficient enantioselective total synthesis of 7‐hydroxyerogorgiaene (8 steps, 29 % overall yield) and 9‐deoxypseudopterosin A (9 steps, 30 % overall yield) was elaborated using an asymmetric cobalt‐catalyzed hydrovinylation (91 % ee) of 3‐methoxy‐4‐methyl‐styrene as the chirogenic step. Other important C−C bond forming steps include a Pd‐catalyzed Suzuki cross‐coupling and diastereoselective Lewis acid‐mediated cyclization reactions. A total of 16 amino derivatives of natural products were prepared and subsequently tested for their antibacterial properties. Some of the diterpene‐derived amines showed high efficacy, not only against Gram‐positive (S. aureus SG511, S. aureus HG003, B. subtilis 168; MIC=0.5 to 2 μg/ml), but also against Gram‐negative bacterial strains (E. coli K12; E. coli I‐11276b; MIC=8 to 32 μg/ml). This clearly supported the underlying working hypothesis.
Psychosocial and psychophysical assessment in paediatric patients and young adults with chronic back pain: A cluster analysis
Authors: Ocay D. D. , Loewen A. , Premachandran S. , Ingelmo P. M. , Saran N. , Ouellet J. A. , Ferland Catherine E.
Published: January 2022

Background

Identifying subgroups with different clinical profiles may inform tailored management and improve outcomes. The objective of this study was to identify psychosocial and psychophysical profiles of children and adolescents with chronic back pain.

Methods

One hundred and ninety‐eight patients with chronic back pain were recruited for the study. Pain assessment was mainly conducted in the form of an interview and with the use of validated pain‐related questionnaires assessing their psychosocial factors and disability. All patients underwent mechanical and thermal quantitative sensory tests assessing detection and pain thresholds, and conditioned pain modulation efficacy.

Results

Hierarchal clustering partitioned our patients into three clusters accounting for 34.73% of the total variation of the data. The adaptive cluster represented 45.5% of the patients and was characterized to display high thermal and pressure pain thresholds. The high somatic symptoms cluster, representing 19.2% of patients, was characterized to use more sensory, affective, evaluative and temporal descriptors of pain, more likely to report their pain as neuropathic of nature, report a more functional disability, report symptoms of anxiety and depression and report poor sleep quality. The pain‐sensitive cluster, representing 35.4% of the cohort, displayed deep tissue sensitivity and thermal hyperalgesia.

Conclusions

This study identified clinical profiles of children and adolescents experiencing chronic back pain based on specific psychophysical and psychosocial characteristics highlighting that chronic pain treatment should address underlying nociceptive and non‐nociceptive mechanisms.

Significance

To our current knowledge, this study is the first to conduct cluster analysis with youth experiencing chronic back pain and displays clinical profiles based on specific physical and psychosocial characteristics. This study highlights that in a clinical context, chronic pain assessment should include multiple elements contributing to pain which can be assessed in a clinical context and addressed when pathoanatomical symptoms are unidentifiable.
Repeating stereotypes: Increased belief and subsequent discrimination
Authors: Oğuz Taşbaş Esra Hatice , Unkelbach Christian
Published: January 2022

People believe repeated information more than novel information. Classic research on this repetition‐induced truth effect used trivia statements as information and truth ratings as the main DV. We investigate how repeating stereotypes about groups influence the stereotypes' believability and decisions about group members. Participants learned positive stereotypes about two groups of aliens. However, for one group, we repeated the stereotypes. Then, participants completed a mock personnel selection task based on short CVs of the aliens. Finally, participants evaluated the truth of the presented stereotypes. Experiment 1 showed a preference for the group with repeated information and increased belief in repeated information. Experiment 2 replicated this pattern and excluded alternative explanations in terms of better memory, evaluative conditioning, and mere exposure. We thereby provide evidence for the repetition‐induced truth effect in the stereotyping domain and show the influence of mere information repetition on subsequent group‐based discriminatory behaviour.
Cyclic behaviour of precast beam‐to‐column connections with low seismic detailing
Authors: Batalha Nádia , Rodrigues Hugo , Arêde António , Furtado André , Sousa Romain , Varum Humberto
Published: January 2022

Beam‐to‐column connections are a crucial element in industrial precast reinforced concrete (PRC) buildings. They are also the source of several damages reported after recent earthquakes. This typology of buildings is very common both in the Portuguese industrial park and throughout Europe. In order to have a better knowledge of the connection behaviour an extensive experimental work was done and it is here presented to characterize, under cyclic loading, the pure friction behaviour and friction and dowel beam–to–column behaviour. The research was focused on the parameters that might influence the seismic performance of the connections. These are the friction between elements, the absence or presence of dowels and their position on the column's corbel, and finally the different axial load level applied on the connections. The results presented in this study pointed to the importance of using neoprene pad between concrete faces, with the main objective of damage control. The use of mechanical connectors (dowels) was also highlighted as a source of increasing the strength of the beam–to–column connection in values greater than 50%.
Data and Diversity in the Development of Acute Water Quality Criteria in the United States
Authors: Coleman Alice L. , Edmands Suzanne
Published: January 2022

The US Environmental Protection Agency (USEPA) is responsible for the development of water quality criteria, regulatory standards that protect aquatic organisms from harmful chemical exposure. Although these criteria are intended to be broadly protective of aquatic life, the data used to derive criteria do not necessarily reflect the actual diversity of natural communities nor are they available for most chemicals. In addition, although the USEPA's current procedures emphasize using toxicity data with a certain minimum amount of biological diversity, the quantitative impact of such diversity on criteria is unclear. In the present study we assessed the changes to acute toxicity data over time, determined the prevalence of significant taxonomic differences in sensitivity, and investigated the effect of biological diversity on criteria. We found major gaps in existing toxicity data that we hypothesize have contributed to the absence of acute criteria for the majority of chemical pollutants. Taxonomic patterns of sensitivity in these data are abundant, although the resolution of the patterns is relatively poor. In addition, we found that the amount of biological diversity in a toxicity data set and the data set's taxonomic composition does not quantitatively affect criteria in most cases. Because the USEPA has published acute criteria for fewer than 20% of priority pollutants and the persistence of major gaps in toxicity data over the last 37 years, we recommend that the USEPA consider revisions to their water quality criteria guidelines that will expedite the criteria development process and advance the responsible management of pollutants in the aquatic environment. Environ Toxicol Chem 2022;41:1333–1343. © 2022 SETAC
Distribution of polyphenolic compounds, antioxidant potential, and free amino acids in Ziziphus fruits extract; a study for determining the influence of wider geography
Authors: Uddin Nisar , Muhammad Noor , Nisar Mohammad , Aisha  , Ali Niaz , Ullah Riaz , Ali Essam A. , Khan Azhar Abbas , Rahman Inayat Ur , Khan Anwar , Zeb Alam
Published: January 2022

Ziziphus fruits have attracted much attention within the field of medicine due to their high potential against central nervous system disorders. Abundance of secondary metabolites and their composition is key to the pharmaceutical potential and commercial qualities of plants. The in vitro antioxidant activities of Ziziphus nummularia (Burm. f.) and Ziziphus oxyphylla Edgew fruit extract were analyzed using 2,2‐diphenil‐1‐pycrilhydrazyl (DPPH) and 2,2′‐azino‐bis (3‐ethylbenzothiazoline)‐6‐sulfonic acid (ABTS) free radical scavenging assay methods. Phenolic profiles were explored using high‐performance liquid chromatography‐diode array detector (HPLC‐DAD). The result revealed high concentration of polyphenols and their antioxidant potential. In Z. nummularia, the total phenolic content (TPC) (80.270 ± 0.422 μg/ml), DPPH (62.03 ± 0.98 μg/ml), ABTS (66.32 ± 0.73 μg/ml), and TFC (90.683 ± 0.274 μg/ml) were recorded. However, in Z. oxyphylla, DPPH and ABTS values were 60.66 ± 0.56 μg/ml and 61.55 ± 0.77 μg/ml, respectively, indicative of the impacts of climate and soil nutrients. The overall screening of phytochemicals revealed that both the Ziziphus species contain diverse bioactive compounds, including spinacetine‐3‐O‐(2 feruloyl glucopyranosyl)‐glucopyranoside, kaempferol‐3‐O‐glucoside‐7‐O‐glucoside, and caffeic acid; p‐hydroxybenzoyl hexose, p‐coumaric acid, salicylic acid, and ellagic acid pentoxide. Additionally, the highest concentrated amino acid noted was of Lue 0.19 g/100 g with 596.00 retention time (RT), followed by Thr>Ale>Isl>Phya>Val in Z. nummularia. Similarly, the highest concentration of Lue amino acid was recorded as 0.18/100 g with 564.52 RT followed by Pr>Thr>Ale>Lue>Isl>Phya>Val in all genotypes of Z. oxyphylla. Reporting of polyphenols rich and stable species along with identification of favorable regions of cultivation for amino acid, polyphenols, and higher antioxidant potential may lead the way for the identification of elite clones of the species as well as may result in new drug discovery.
Effects of the Covid‐19 pandemic on derivatives markets: Evidence from global futures and options exchanges
Authors: Emm Ekaterina E. , Gay Gerald D. , Ma Han , Ren Honglin
Published: January 2022

We examine key developments in trade‐related activity on global derivatives markets during the Covid‐19 pandemic. We first document significant increases in volumes and open interest. Drawing upon techniques from network theory, we next find greater market interconnectedness and notable changes in market centrality. For US exchanges, we examine their response to the increased market uncertainty and find large and more frequent changes to margin requirements. We also find a considerable drop in trader participation driven mainly by noncommercial traders along with an increase in the percent of open interest held by commercial shorts and noncommercial longs.
Dating stone arrangements using optically stimulated luminescence and fallout radionuclides
Authors: Kemp Justine , Olley Jon , Stout Justin , Pietsch Timothy ,   Mithaka Aboriginal Corporation
Published: January 2022

Buildings and monuments constructed from stone provide some of the best‐preserved surface archaeology, but their construction ages can be difficult to determine using radiocarbon techniques. In Australia, stone arrangements are recognised as architectural or symbolic features belonging to Aboriginal societies. The structures are predominantly inorganic with shallow infill, hampering attempts to determine their antiquity. Optically stimulated luminescence (OSL) techniques have the potential to date these features, but their complex geometry requires careful consideration of the background radiation. Here, we present the first ages for Australian Aboriginal stone construction using single‐grain OSL techniques on quartz from stone arrangements in central Australia. Beta and gamma dose rates and the cosmic ray dose have been estimated from mapping the gross geometry of stone and sand courses. The resulting OSL ages are internally consistent and, together with fallout radionuclides137Cs and210Pb, indicate a minimum age for construction between 1959 and 1981 AD. We demonstrate that single‐grain OSL techniques can be used to determine the age of emplaced sand between stones and, assuming a stable substrate, can be used to date stone building construction as well as building occupation, providing chronologies for sites where organic material for radiocarbon analysis is limited or unavailable.
Viral mediated knockdown of GATA6 in SMA iPSC‐derived astrocytes prevents motor neuron loss and microglial activation
Authors: Allison Reilly L. , Welby Emily , Khayrullina Guzal , Burnett Barrington G. , Ebert Allison D.
Published: January 2022

Spinal muscular atrophy (SMA), a pediatric genetic disorder, is characterized by the profound loss of spinal cord motor neurons and subsequent muscle atrophy and death. Although the mechanisms underlying motor neuron loss are not entirely clear, data from our work and others support the idea that glial cells contribute to disease pathology. GATA6, a transcription factor that we have previously shown to be upregulated in SMA astrocytes, is negatively regulated by SMN (survival motor neuron) and can increase the expression of inflammatory regulator NFκB. In this study, we identified upregulated GATA6 as a contributor to increased activation, pro‐inflammatory ligand production, and neurotoxicity in spinal‐cord patterned astrocytes differentiated from SMA patient induced pluripotent stem cells. Reducing GATA6 expression in SMA astrocytes via lentiviral infection ameliorated these effects to healthy control levels. Additionally, we found that SMA astrocytes contribute to SMA microglial phagocytosis, which was again decreased by lentiviral‐mediated knockdown of GATA6. Together these data identify a role of GATA6 in SMA astrocyte pathology and further highlight glia as important targets of therapeutic intervention in SMA.
Insight into the dynamics of micropolar fluid about a vertical cone when nonlinear thermal radiation is significant: The case of triple mixed convection
Authors: Patil P. M. , Shankar H. F.
Published: January 2022

This novel research investigates the nonlinear triple diffusive combined convective micropolar liquid flow past a vertical cone in the presence of nonlinear thermal radiation, cross‐diffusion, and a convective boundary condition. We aim to analyze this present problem using nonsimilar transformations. This report presents the significance of nonlinear mixed convection, energy flux due to the concentration gradient, and mass flux due to the temperature gradient and nonlinear thermal radiation in the dynamics of the fluid subject with micropolar fluid is presented. The differential equations defining the boundary‐layer parameters are then transformed into dimensionless view, taking into account the nonsimilar transformation. Furthermore, the method of quasilinearization and implicit finite difference approximation is used to work out the nondimensional governing equations for the solution. The velocity pattern diminishes, while dimensionless temperature and concentration distributions enhance with growing values of microrotation parameter. Furthermore, species concentrations of the fluid increase with increasing Soret effect values, while opposite results appear for mass transfer rates. Also, drag coefficient enhances for assisting buoyancy flow whilst diminishes for opposing buoyancy flow with increasing values of the microrotation parameter. The microrotation pattern reduces with growing values of the nonsimilarity characteristics. Furthermore, the Prandtl number is displayed on a comparison graph, and the results are very similar.
Association of serotonin transporter gene polymorphism with efficacy of the antidepressant drugs sertraline and mirtazapine in newly diagnosed patients with major depressive disorders
Authors: Gulfishan Syed , Halder Sumita , Kar Rajarshi , Srivastava Shruti , Gupta Rachna
Published: January 2022

Objective

We examined the association of serotonin receptor transporter gene polymorphism in patients with MDD with the clinical efficacy of mirtazapine (MZ) and sertraline (ST).

Method

Newly diagnosed, treatment naïve, 80 MDD patients (aged 18–45) diagnosed using DSM‐5 criteria and with Beck's depression inventory score (BDI) score ≥21 were included and randomly divided into two groups of 40 participants and were administered MZ 15–45 mg/day or ST 25–200 mg/day respectively. Patients were followed up for 6 weeks for evaluation of BDI scores. Genotypic evaluation was done and three allele variants were identified based on the polymerase chain reaction fragment sizes: short (S; 486 bp), long (L; 529 bp), or extralong (XL; 612 or 654 bp) and classified into five genotypes: S/S,S/L, L/L, S/XL, and L/XL.

Result

We found that 32.5% patients belonged to the S/S genotype, suggesting that individuals with the SS genotype are at higher risk of developing MDD. No statistically significant association was seen with ST or MZ groups on the basis of genotypes. Clinically significant improvement was observed with a more than 50% reduction in BDI scores at 6 weeks of treatment with both drugs.

Conclusion

Identification of risk population can be carried out by genotype testing. Prior genotyping in MDD patients might help to predict a better clinical outcome with antidepressants.
Utility of the avian sub-acute dietary toxicity test in ecological risk assessment and a path forward to reduce animal use
Authors: Bone Audrey J. , Brewer Larry , Habig Cliff , Levine Steve L. , Moore Dwayne R. J. , Plautz Stephanie
Published: January 2022

The United States Environmental Protection Agency (USEPA) has long required both avian sub-acute dietary and acute oral studies to inform risk assessments for pesticides. Recently, the USEPA collaborated with People for the Ethical Treatment of Animals to determine whether the results of the acute oral avian toxicity test or the sub-acute dietary toxicity test consistently generated the greatest risk predictions in USEPA tier 1 assessments for pesticides first registered between 1998 and 2017. Their study concluded that in 99% of the cases, risk conclusions were driven by the acute oral study (OPPTS 850.2100, OCSPP 850.2100, or similar) because using these data results in higher risk quotients than sub-acute dietary data. Shortly after publishing these results, the USEPA released a formal memorandum providing guidance for waiving the sub-acute dietary study for most pesticides. The USEPA will, however, retain the option to require sub-acute dietary studies for pesticides with certain chemical properties. However, as the avian sub-acute dietary study has an exposure regimen that is often more representative of how birds are exposed to pesticides under actual use conditions than does the acute oral study (i.e., as part of a dietary item eaten over the course of a day and not a bolus dose), this study can provide useful context for risk assessment on a case-by-case basis. Decision criteria are needed to determine a path forward that both minimizes vertebrate animal testing and positions the avian sub-acute dietary data as an option for risk refinement. Decision criteria are proposed here with recommendations for refining the design of avian sub-acute dietary studies to ensure that the data generated are optimized to support a science-based acute avian risk assessment, supported by a case study demonstrating when and how sub-acute dietary studies may be used in a higher-tier risk assessment. Integr Environ Assess Manag 2022;18:1629–1638. © 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

KEY POINTS

Given recent guidance from the USEPA on waiving the avian sub-acute dietary study for pesticide registration, this article provides recommendations for the use of this study as a risk refinement option.
An all‐inclusive computer‐aided melanoma diagnosis based on soft computing
Authors: Jiao Xiongfei , Li Juan , Zhao Zhilei , Badami Benjamin
Published: January 2022

This paper provides a different optimized approach for melanoma diagnosis from the inputted dermoscopy images. The technique is a pipeline technique with four main steps, including noise reduction, lesion segmentation, feature selection, and final classification. For decreasing the complexity of the feature extraction stage, Fuzzy C‐means has been used. The classifier has been improved based on a developed decision tree. The modification of the classifier is based on a new enhanced design of a metaheuristic, called Quantum Fluid Search Optimizer. The efficiency of the suggested technique is calculated by considering some measurement indicators and their achievements are compared with five other latest methods. The results showed the maximum accuracy equal to 94.12% with the highest precision being achieved by the proposed method. The results also indicate that the proposed method with the highest value of 91.18% sensitivity against the other techniques, provides the highest reliability.
Using the River Ecosystem Service Index to evaluate “Free Moving Rivers” restoration measures: A case study on the Ammer river (Bavaria)
Authors: Becker Isabell , Egger Gregory , Gerstner Lars , Householder John Ethan , Damm Christian
Published: January 2022

Restoring natural fluvial dynamics is fundamental for sustaining biodiversity and functional integrity of river and floodplain ecosystems. In Central Europe, however, pervasive river regulation and bank protection have greatly impaired ecosystem functioning and many water bodies fail to achieve a good ecological status within the European Water Framework Directive. The “Free Moving Rivers” approach seeks to restore the ecological integrity of rivers and floodplains by creating appropriate conditions for natural fluvial dynamics. Principal goals of the approach include removing artificial constraints on river processes and expanding the river corridor to restore natural river habitats and structures. Lacking, however, are complementary tools that evaluate and predict changes to ecosystem services (ESSs) after implementation. Here, we describe a case study of the Ammer river in Bavaria, Germany, to (i) calculate the extent of the “Free Moving Rivers” corridor, and (ii) assess changes to ESSs of a proposed river restoration measure under two alternative land‐use scenarios. To do this, we apply the River Ecosystem Service Index (RESI), whereby individual ESSs are assessed in a spatially explicit way. We show how a proposed implementation of the “Free Moving Rivers” approach enhances three investigated ESSs: flood retention, sediment balance and habitat provision. We conclude that RESI is a potentially useful tool with wide applicability for restoration planning that synthesises floodplain complexity in such a way that facilitates decision making.
Efficient activation of peroxymonosulfate by 3D hollow petal‐like spherical NiCo2O4 nanomaterials for the decomposition of phenol solution: performance and mechanism
Authors: Lu Lingzhu , Yue Lijuan , Hao Liangyun , Niu Weibing , Cheng Ping , Zhu Yuanzheng , Zhang Shuping , Chen Chunguang
Published: January 2022

BACKGROUND

Phenolic pollutant contamination is a serious problem. The advanced oxidation process based on sulfate radicals (SR‐AOPs) is an efficient technology for the degradation of phenolic contaminants in the aquatic environment. Bimetallic nanomaterials have attracted much attention because of their excellent catalytic performance in activating peroxymonosulfate (PMS). Herein, 3D mesoporous NiCo2O4 hollow petal spheres with a specific surface area of 252.35 m2 g−1 were successfully prepared.

RESULTS

In the NiCo2O4/PMS system, phenol (50 mg L−1) was absolutely removed within 25 min with a degradation rate constant (k) of 0.19651 min−1, which is 6.2 times higher than that of the Co3O4/PMS system. The excellent catalytic activity of NiCo2O4 is attributed to the larger amount of redox cycles of Co3+/Co2+ and Ni3+/Ni2+ as well as its large specific surface area and multi‐step pore channel structure. Moreover, the related influencing factors were systematically researched in the NiCo2O4/PMS system, including reaction temperature, solution pH, initial concentration, catalyst and PMS dose, as well as matrix species (HCO3−, Cl−, NO3−, and humic acid). The recycling tests revealed the outstanding chemical stability of NiCo2O4. The electron paramagnetic resonance (EPR) and quenching experiments verify that sulfate radical (SO4• −) acts as the leading role for phenol decomposition. The possible degradation path was proposed based on the several major degradation intermediates that were detected by Gas Chromatography‐Mass Spectrometer (GC–MS).

CONCLUSION

This research provides a facile and mild method for the fabrication of promising 3D heterogeneous catalysts for PMS activation and provides a green and promising technology for effective contaminant control in modern wastewater remediation. © 2022 Society of Chemical Industry (SCI).
Cellular architecture of the testis of Egyptian wild boar (Sus scrofa) in young and adult age
Authors: Elghoul Mahmoud M. , Zaghloul Doaa M. , Morsy Kareem , Abumandour Mohamed M. A.
Published: January 2022

Testicular parenchyma is split into lobules, each lobule contains convoluted seminiferous tubules surrounded by myoid cells and the interstitial tissue contains groups of Leydig cells. The seminiferous tubules are lined by two groups of cells the first one is the spermatogenic cells and the second one is Sertoli cells.
Spontaneous portosystemic shunt diameter predicts liver function after balloon‐occluded retrograde transvenous obliteration
Authors: Tatsumi Akihisa , Maekawa Shinya , Osawa Leona , Katoh Ryo , Komiyama Yasuyuki , Nakakuki Natsuko , Takada Hitomi , Matsuda Shuya , Muraoka Masaru , Suzuki Yuichiro , Sato Mitsuaki , Takahashi Ei , Miura Mika , Amemiya Fumitake , Takano Shinichi , Fukasawa Mitsuharu , Yamaguchi Tatsuya , Nakayama Yasuhiro , Inoue Taisuke , Okada Hiroki , Araki Takuji , Onishi Hiroshi , Enomoto Nobuyuki
Published: January 2022

Background and Aim

Recently, balloon‐occluded retrograde transvenous obliteration (BRTO), performed for spontaneous portosystemic shunts (SPSS), has been receiving attention as a measure to improve liver function in cirrhotic patients with portal hypertension. However, it is unclear whether SPSS diameter is associated with changes in hepatic venous pressure gradient (HVPG) and liver function after BRTO.

Methods

In 34 cirrhotic patients receiving BRTO for hepatic encephalopathy/gastric varices, the association of SPSS diameter with liver function at baseline and 6 months after BRTO and the accompanying changes in HVPG were investigated.

Results

Patients had Child–Pugh (CP) scores of A/B/C (7/19/8), SPSS diameters of ≤10 mm/11–20 mm/<20 mm (8/21/5), and an average observation period of 3.2 (0.3–8.5) years. SPSS diameter was significantly associated with male sex, alcohol use, and values of albumin, prothrombin time (PT%), and NH3 at baseline. Moreover, the SPSS diameter was significantly correlated with the changes in HVPG observed upon BRTO (r = 0.55, P = 0.005), and a large shunt diameter was significantly associated with a greater increase in HVPG. At 6 months, significant improvements in albumin, PT%, bilirubin, and NH3 were observed overall, but the improvement was marked in those with larger shunt diameters if they had CP A/B.

Conclusion

SPSS diameter was strongly associated with liver function at baseline and after BRTO and also with changes in HVPG, indicating that SPSS diameter is an important predictor of BRTO outcome.
Loading of cell cultures with cholesterol‐dextran particles as a new functional test for Niemann–Pick type C disease
Authors: Majer Filip , Asfaw Befekadu , Kuchař Ladislav , Mušálková Dita , Steiner‐Mrázová Lenka , Dobrovolný Robert , Ledvinová Jana , Hřebíček Martin
Published: January 2022

Deuterium‐labeled cholesterol‐dextran particles (d4‐CholDex), prepared by co‐precipitation, were internalized by cultured human skin fibroblasts and HEK293 cells. Subcellular particles from d4‐CholDex‐treated HEK293 cells were fractionated on iodixanol gradients. More than 60% of d4‐cholesterol (d4‐UC) in the gradient co‐fractionated with lysosomal markers and NPC1. This and formation of d4‐cholesteryl esters (d4‐CE) in the cells suggests that d4‐CholDex is lysosomally processed. In accordance with these findings, we observed an increase in lysosomal cholesterol content by fluorescence microscopy in CholDex‐loaded cells. Fibroblast cultures including 13 NPC1‐deficient, four heterozygous and six control lines were treated with d4‐CholDex at final d4‐UC concentration of 0.05 mg/ml (127.98 μmol/L) for 3 h and chased for 48 h in medium without d4‐CholDex. Concentrations of d4‐UC and d4‐CE in harvested cells were measured by tandem mass spectrometry (MS/MS). d4‐UC/d4‐CE ratios were elevated in NP‐C lines compared to controls (n = 6, mean = 4.36, range = 1.89–8.91), with the highest ratios in severe NP‐C1 phenotypes and the lowest in adolescent/adult type patients. There were overlaps between NP‐C1 forms: early infantile (n = 1, mean = 48.6), late infantile (n = 4, mean = 36.3, range = 20.6–54.0), juvenile (n = 5, mean = 24.7, range = 13.4–38.3), adolescent/adult (n = 3, mean = 14.5, range = 11.7–19.8). The ratios in NP‐C1 heterozygotes were mildly elevated (n = 4, mean = 16.4, range = 14.9–17.4) and comparable to patients with adolescent/adult NP‐C1. The test can be useful in evaluation of suspected NP‐C patients with inconclusive results of biomarker or molecular tests. Its advantages include standardized preparation of particles with longer shelf life at 4 °C, quantitative results, and no requirement for radioactive chemicals.
Original and alteration mineral phases in the NWA 10628 Martian shergottite determined by micro‐Raman spectroscopy assisted with micro‐energy dispersive X‐ray fluorescence imaging
Authors: Prieto‐delaVega Itziar , García‐Florentino Cristina , Torre‐Fdez Imanol , Huidobro Jennifer , Aramendia Julene , Arana Gorka , Castro Kepa , Madariaga Juan Manuel
Published: January 2022

NorthWest Africa 10628 (NWA 10628) is a shergottite found in Tindouf (Algeria) in 2014. Little is known on this meteorite apart from the Meteoritical Bulletin report. In this work, original and altered mineral phases of NWA 10628 were characterised by micro‐Raman spectroscopy assisted with micro‐energy dispersive X‐ray fluorescence imaging. The matrix of the meteorite is dominated by high‐Ca pyroxenes, augite ((Ca,Na)(Mg,Fe,Al,Ti)(Si,Al)2O6) and diopside (CaMgSi2O6). Olivine and feldspars appeared as small crystals all along the matrix. Merrillite (Ca9NaMg(PO4)7) was found as big crystals in inclusions. As whitlockite (Ca9NaMg(PO4)6(HPO4)) can be transformed into merrillite at high temperature and pressure, we suggest that merrillite in the meteorite was originally whitlockite, before its ejection from Mars. Gypsum (CaSO4·2H2O) was found as small crystals and in fractures; this last one could come from terrestrial weathering because it was associated with calcite (CaCO3). Small anhydrite (CaSO4) crystals are shown in the bulk together with gypsum, probably from the partial dehydration of original Martian gypsum by the high‐pressure/temperature of ejection. Pyrite and marcasite (FeS2 polymorphs) minerals were detected, as well as their oxidation products, goethite (α‐FeO (OH)) and rozenite (FeSO4·4H2O), due to their terrestrial weathering. The identification of hematite (Fe2O3), magnetite (Fe3O4), ilmenite (FeTiO3) and anatase (TiO2) suggested that ulvospinel (Fe2TiO4) was the precursor on Mars, because ulvospinel is transformed into ilmenite by pressure and later ilmenite can be altered to magnetite/hematite and anatase by oxidative weathering on Earth. This non‐destructive analytical methodology provides deep mineralogical characterisation adequate for scarce samples like those returning from the Mars Sample Return mission.
New York MH advocates laud investments in proposed budget
Authors: Canady Valerie A.
Published: January 2022

New York state advocates and providers say they are pleased with the governor's attentiveness to a long‐overdue cost‐of‐living adjustment (COLA) increase, support of retention and recruitment of the health care workforce, and monitoring and enforcement of Medicaid managed care behavioral health services.
School closures during COVID lockdown impacting student MH
Authors: Canady Valerie A.
Published: January 2022

School closures as part of broader social lockdown measures during the COVID‐19 pandemic may be associated with a decline in the health and well‐being of children and adolescents, according to new research published in JAMA Pediatrics. Researchers found that the pandemic caused significant damage to children's mental health.