Miracle-dz/UniFAR-FTUs huggingface dataset:
Concordance of Programmed Death-Ligand 1 Expression between SP142 and 22C3/SP263 Assays in Triple-Negative Breast Cancer

Purpose Triple-negative breast cancer (TNBC) represents a major clinical challenge due to its aggressive and metastatic behavior and the lack of available targeted therapies. Therefore, therapeutic strategies are needed to improve TNBC patient management. Recently, atezolizumab and nab-paclitaxel chemotherapy has been approved by the Food and Drug Administration for the first-line treatment of patients with locally advanced and metastatic TNBC. The programmed death-ligand 1 (PD-L1) immunohistochemical SP142 assay was also approved as a companion diagnostic device for selecting TNBC patients for atezolizumab treatment. This study aimed to evaluate and compare the analytical performance of the PD-L1 22C3/SP263 assays in comparison with the SP142 assay for ≥ 1% immune cells (ICs). Methods Immunohistochemical expression for the PD-L1 22C3/SP263 assays, in comparison with the SP142 assay, was analyzed for the ≥ 1% ICs in 95 TNBCs. Results At the 1% cut-off value, the proportions of positive cases were 52.6% for the SP142 assay in infiltrating ICs and 50.5% and 52.6% for the 22C3 and SP263 assays in tumor cells, respectively. The PD-L1 SP263 assay had the highest while the PD-L1 22C3 assay had the lowest total positive expression rate at all cut-off values. The concordance rate between the assays was highest at a 1% cut-off value and decreased when the cut-off value increased. The concordance rate between the SP142 and SP263 assays at 1% cut-off was high, while in comparison, the concordance rate between the SP142 and 22C3 assays at 1% cut-off was relatively lower. Conclusion This study demonstrates that although the 22C3 assay at a 1% cut-off value compared with the PD-L1 SP142 assay at the clinically relevant cut-off shows comparable but not interchangeable analytical performance, the analytical performance of the SP263 assay at a 1% cut-off value shows interchangeable performance with the PD-L1 SP142 assay at the clinically relevant cut-off.
Suicide prevention skills, confidence and training: Results from the Zero Suicide Workforce Survey of behavioral health care professionals

Introduction: In behavioral health care settings, a workforce well trained in suicide prevention is critically important for behavioral health care professionals across different disciplines and service sectors who are likely to have considerable exposure to patients at risk for suicidal behavior. This study examined the types of training behavioral health care professionals received, their self-reported skills, comfort level and confidence related to suicide prevention, the association of types and length of training with skills, comfort level and confidence, and areas in which participants would like more training. Methods: The Zero Suicide Workforce Survey was administered electronically to behavioral health care professionals at six behavioral health treatment centers with both inpatient and ambulatory programs in Connecticut, USA. Item numbers and percentages were calculated for 847 respondents with behavioral health care roles. The chi-square tests were performed to determine the statistical significance of group differences. Non-parametric sign tests were performed to determine the statistical significance of the collective differences in direction among items between groups. Results: Suicide prevention training is associated with increased levels of behavioral health care professionals’ skills and confidence, but one-third of behavioral health care professionals in the sample received no formal training in suicide prevention/intervention. Even brief training appears to have a positive impact on behavioral health care professionals’ assessment of their skills and confidence. Prominent topics for additional training include suicide-specific treatment approaches, suicide prevention and awareness, and identification of risk factors and warning signs. Conclusion: Although behavioral health care professionals may often encounter patients at risk for suicide, many have not obtained any relevant training. The findings highlight the need to strengthen suicide identification, assessment and treatment within behavioral health care treatment settings as part of an effort to prevent suicide.
Emergence of HIV-1 C/A1 and C/A1/D circulating recombinant forms, and dominance of subtype C and R5 use from whole genome sequence analysis in Addis Ababa

Background The HIV pandemic in Ethiopia is dominated by subtype C with sporadic A and D epidemiology. The presence of subtypes A and D may result in emergence of recombinant viruses, and increase the genetic diversity that makes monitoring the HIV epidemic, and the development of vaccines and therapeutics difficult. This study is aimed at determining subtypes, circulating recombinant forms (CRFs), and the dominant coreceptor use in Addis Ababa, Ethiopia. Methods Participants with a range of purposely selected CD4+ T-cell counts were included. Chi-square and Mann-Whitney tests were used. Whole genome next-generation sequencing (NGS) of HIV was performed using a PCR amplification method and Illumina MiSeq. Subtyping and scanning of recombination were done by the REGA subtyping tool version 3.0. Prediction of coreceptor usage was performed using Geno2Pheno clonal-model and PhenoSeq. Signature amino acids and positive charges were also used in the tropism prediction. Phylogenetic analyses were conducted with MEGA version 6 using maximum likelihood with the neighbor-joining (N-J) methods. Results Sixty participants were included with a median age of 34.5 [interquartile range (IQR) 30.0-40.0]. Seven (11.7%) of the study participants were at WHO clinical stage 3/4 and 13 (21.7%) were at AIDS stage with CD4+ T cell count <200 cells/uL. Among the total 60 HIV genomes sequenced, 49 were subtype C (81.7%), one was subtype A1 (1.7%), six were recombinant C/A1 (10%), three were recombinant C/A1/D (5.0%), and one was unassigned. From 50 of the sequences where coreceptor usage was determined by PhenoSeq, 44 (88.0%) were CCR5-tropic and six (12.0%) used CXCR4. Conclusion The study confirmed that the dominant subtype in Addis Ababa is HIV-1 subtype C. In addition, HIV-1 subtype A1, CRFs C/A1 and C/A1/D were also identified. The dominance of R5-tropic viruses was detected and these were associated with a higher CD4 T-cell count and lower viral load. Further studies on HIV subtypes and CRFs will be essential to fully understand HIV/AIDS epidemiology. In addition, the tropism information is important in Ethiopia if the use of the co-receptor antagonist maraviroc is planned.
Arbuscular mycorrhizal fungi benefit from 7 years of free air CO2 enrichment in well‐fertilized grass and legume monocultures

Rising atmospheric carbon dioxide partial pressure (pCO2) and nitrogen (N) deposition are important components of global environmental change. In the Swiss free air carbon dioxide enrichment (FACE) experiment, the effect of altered atmospheric pCO2 (35 vs. 60 Pa) and the influence of two different N‐fertilization regimes (14 vs. 56 g N m−2 a−1) on root colonization by arbuscular mycorrhizal fungi (AMF) and other fungi (non‐AMF) of Lolium perenne and Trifolium repens were studied. Plants were grown in permanent monoculture plots, and fumigated during the growth period for 7 years. At elevated pCO2 AMF and non‐AMF root colonization was generally increased in both plant species, with significant effects on colonization intensity and on hyphal and non‐AMF colonization. The CO2 effect on arbuscules was marginally significant (P=0.076). Moreover, the number of small AMF spores (≤100 μm) in the soils of monocultures (at low‐N fertilization) of both plant species was significantly increased, whereas that of large spores (>100 μm) was increased only in L. perenne plots. N fertilization resulted in a significant decrease of root colonization in L. perenne, including the AMF parameters, hyphae, arbuscules, vesicles and intensity, but not in T. repens. This phenomenon was probably caused by different C‐sink limitations of grass and legume. Lacking effects of CO2 fumigation on intraradical AMF structures (under high‐N fertilization) and no response to N fertilization of arbuscules, vesicles and colonization intensity suggest that the function of AMF in T. repens was non‐nutritional. In L. perenne, however, AM symbiosis may have amended N nutrition, because all root colonization parameters were significantly increased under low‐N fertilization, whereas under high‐N fertilization only vesicle colonization was increased. Commonly observed P‐nutritional benefits from AMF appeared to be absent under the phosphorus‐rich soil conditions of our field experiment. We hypothesize that in well‐fertilized agricultural ecosystems, grasses benefit from improved N nutrition and legumes benefit from increased protection against pathogens and/or herbivores. This is different from what is expected in nutritionally limited plant communities.
Pharmacokinetics Alterations in Critically Ill Pediatric Patients on Extracorporeal Membrane Oxygenation: A Systematic Review

Objectives: This study aimed to identify alterations in pharmacokinetics in children on extracorporeal membrane oxygenation (ECMO), identify knowledge gaps, and inform future pharmacology studies. Data Sources: We systematically searched the databases MEDLINE, CINAHL, and Embase from earliest publication until November 2018 using a controlled vocabulary and keywords related to “ECMO” and “pharmacokinetics,” “pharmacology,” “drug disposition,” “dosing,” and “pediatrics. ” Study Selection: Inclusion criteria were as follows: study population aged <18 years, supported on ECMO for any indications, received any medications while on ECMO, and reported pharmacokinetic data. Data Extraction: Clearance and/or volume of distribution values were extracted from included studies. Data Synthesis: Forty-one studies (total patients = 574) evaluating 23 drugs met the inclusion criteria. The most common drugs studied were antimicrobials (n = 13) and anticonvulsants (n = 3). Twenty-eight studies (68%) were conducted in children <1 year of age. Thirty-three studies (80%) were conducted without intra-study comparisons to non-ECMO controls. Increase in volume of distribution attributable to ECMO was demonstrated for nine (56%) drugs: cefotaxime, gentamicin, piperacillin/tazobactam, fluconazole, micafungin, levetiracetam, clonidine, midazolam, and sildenafil (range: 23–345% increase relative to non-ECMO controls), which may suggest the need for higher initial dosing. Decreased volume of distribution was reported for two drugs: acyclovir and ribavirin (50 and 69%, respectively). Decreased clearance was reported for gentamicin, ticarcillin/clavulanate, bumetanide, and ranitidine (range: 26–95% decrease relative to non-ECMO controls). Increased clearance was reported for caspofungin, micafungin, clonidine, midazolam, morphine, and sildenafil (range: 25–455% increase relative to non-ECMO controls). Conclusions: There were substantial pharmacokinetic alterations in 70% of drugs studied in children on ECMO. However, studies evaluating pharmacokinetic changes of many drug classes and those that allow direct comparisons between ECMO and non-ECMO patients are still lacking. Systematic evaluations of pharmacokinetic alterations of drugs on ECMO that incorporate multidrug opportunistic trials, physiologically based pharmacokinetic modeling, and other methods are necessary for definitive dose recommendations. Trial Registration Prospero Identifier: CRD42019114881.
Genome-Wide Identification, Evolution, and Expression of GDSL-Type Esterase/Lipase Gene Family in Soybean

GDSL-type esterase/lipase proteins (GELPs) belong to the SGNH hydrolase superfamily and contain a conserved GDSL motif at their N-terminus. GELPs are widely distributed in nature, from microbes to plants, and play crucial roles in growth and development, stress responses and pathogen defense. However, the identification and functional analysis of GELP genes are hardly explored in soybean. This study describes the identification of 194 GELP genes in the soybean genome and their phylogenetic classification into 11 subfamilies (A–K). GmGELP genes are disproportionally distributed on 20 soybean chromosomes. Large-scale WGD/segmental duplication events contribute greatly to the expansion of the soybean GDSL gene family. The Ka/Ks ratios of more than 70% of duplicated gene pairs ranged from 0.1–0.3, indicating that most GmGELP genes were under purifying selection pressure. Gene structure analysis indicate that more than 74% of GmGELP genes are interrupted by 4 introns and composed of 5 exons in their coding regions, and closer homologous genes in the phylogenetic tree often have similar exon-intron organization. Further statistics revealed that approximately 56% of subfamily K members contain more than 4 introns, and about 28% of subfamily I members consist of less than 4 introns. For this reason, the two subfamilies were used to simulate intron gain and loss events, respectively. Furthermore, a new model of intron position distribution was established in current study to explore whether the evolution of multi-gene families resulted from the diversity of gene structure. Finally, RNA-seq data were used to investigate the expression profiles of GmGELP gene under different tissues and multiple abiotic stress treatments. Subsequently, 7 stress-responsive GmGELP genes were selected to verify their expression levels by RT-qPCR, the results were consistent with RNA-seq data. Among 7 GmGELP genes, GmGELP28 was selected for further study owing to clear responses to drought, salt and ABA treatments. Transgenic Arabidopsis thaliana and soybean plants showed drought and salt tolerant phenotype. Overexpression of GmGELP28 resulted in the changes of several physiological indicators, which allowed plants to adapt adverse conditions. In all, GmGELP28 is a potential candidate gene for improving the salinity and drought tolerance of soybean.
Menstrual Cycle Effects on Exercise-Induced Fatigability

Estrogen and progesterone have distinct concentrations across the menstrual cycle, each one promoting several physiological alterations other than preparing the uterus for pregnancy. Whether these physiological alterations can influence motor output during a fatiguing contraction is the goal of this review, with an emphasis on the obtained effect sizes. Studies on this topic frequently attempt to report if there is a statistically significant difference in fatigability between the follicular and luteal phases of the menstrual cycle. Although the significant difference (the P-value) can inform the probability of the event, it does not indicate the magnitude of it. We also investigated whether the type of task performed (e.g., isometric vs. dynamic) can further influence the magnitude by which exercise-induced fatigue changes with fluctuations in the concentration of ovarian hormones. We retrieved experimental studies in eumenorrheic women published between 1975 and 2019. The initial search yielded 921 studies, and after manual refinement, 46 experimental studies that reported metrics of motor output in both the follicular and luteal phases of the menstrual cycle were included. From these retrieved studies, 15 showed a statistical difference between the luteal and follicular phases (seven showing less fatigability during the luteal phase and eight during the follicular phase). The effect size was not consistent across studies and with a large range (-6.77; 1.61, favoring the luteal and follicular phase, respectively). The inconsistencies across studies may be a consequence of the differences in the limb used during the fatiguing contraction (upper vs. lower extremity), the type of contraction (isometric vs. dynamic), the muscle mass engaged (single limb vs. full body), and the techniques used to define the menstrual cycle phase (e.g., serum concentration vs. reported day of menses). Further studies are required to determine the effects of a regular menstrual cycle phase on the exercise-induced fatigability.
Geographic Distribution, Ecology, and Phylogenetic Affinities of Thyroptera lavali Pine 1993

Thyroptera lavali (Chiroptera: Thyropteridae) is a rare Neotropical species that until now has been recorded from only five localities in the Amazonian rainforests of Peru, Ecuador, Venezuela, and Brazil. Fewer than 10 specimens of T. lavali exist and, accordingly, little is known about its distribution, natural history, and phylogenetic affinities. We report new records for the species from southeastern Peru. Together with other recently published records, these expand the known range of the species considerably, as well as increase our knowledge of its ecology. Thyroptera lavali seems to prefer primary forest near swamps, and probably roosts in palms; its reproductive pattern is similar to that of other Neotropical insectivorous bats, with parturition at the beginning of wet season. Finally, we used two different data matrices to assess its phylogenetic relationships: one of discrete morphological characters, the other of DNA sequences of mitochondrial genes. Both data sets support a sister relationship between T. lavali and T. tricolor, with T. discifera as the basal member of the genus Thyroptera.
Role of Calcitonin Gene-Related Peptide in Nociceptive Modulationin Anterior Cingulate Cortex of Naïve Rats and Rats With Inflammatory Pain

It is known that calcitonin gene-related peptide (CGRP) plays a key role in pain modulation in the brain. There are high expressions of CGRP and CGRP receptor in anterior cingulate cortex (ACC), an important brain structure in pain modulation. The present study explored the role and mechanisms of CGRP and CGRP receptor in nociceptive modulation in ACC in naïve rats and inflammatory rats. Administration of different does of CGRP in ACC induced significant antinociception in a dose-dependent manner in both naïve rats and rats with inflammatory pain. The CGRP-induced antinociception was attenuated by injection of the CGRP receptor antagonist CGRP8-37 in ACC. Interestingly, both CGRP-induced antinociception and CGRP receptor expression decreased in ACC in rats with inflammatory pain compared with naïve rats. Knockdown of CGRP receptor in ACC by siRNA targeting to CGRP receptor attenuated both the CGRP receptor expression and the CGRP-induced antinociception significantly in rats. These findings demonstrate that CGRP and CGRP receptor participate in nociceptive modulation in ACC in rats, inhibiting CGRP receptor expression induces decrease in CGRP-induced antinociception in ACC.
Mismatch Repair Pathway, Genome Stability and Cancer

The acquisition of genomic instability is one of the key characteristics of the cancer cell, and microsatellite instability (MSI) is an important segment of this phenomenon. This review aims to describe the mismatch DNA repair (MMR) system whose deficiency is responsible for MSI and discuss the cellular roles of MMR genes. Malfunctioning of the MMR repair pathway increases the mutational burden of specific cancers and is often involved in its etiology, sometimes as an influential bystander and sometimes as the main driving force. Detecting the presence of MSI has for a long time been an important part of clinical diagnostics, but has still not achieved its full potential. The MSI blueprints of specific tumors are useful for precize grading, evaluation of cancer chance and prognosis and to help us understand how and why therapy-resistant cancers arise. Furthermore, evidence indicates that MSI is an important predictive biomarker for the application of immunotherapy.
Risk for Behavioral Problems Independent of Cognitive Functioning in Children Born at Low Gestational Ages

This study aimed to investigate cognitive and behavioral outcomes in relation to gestational age (GA) in school-aged children born preterm (PT). Results from the Wechsler Intelligence Scale for Children, 4th edition (WISC-IV), and the Child Behavior Checklist (CBCL) were analyzed in 51 children (mean age: 7.8 years [range: 7.0–8.7]) born PT (mean GA: 31 weeks [range: 23–35]; birth weight, mean: 1,637 g [range: 404–2,962]) with the majority (96%) having no diagnosed cognitive, sensory, or motor impairments. The control group included 57 age-matched typically developing children (mean age: 7.9 years [range: 6.2–8.7]) born full-term (FT). Children born PT, extremely PT (GA < 28) in particular, showed significantly lower cognitive performance and higher behavioral problem scores compared with children born FT. GA was found to predict aspects of both cognitive functioning and behavioral problems within the PT group, with lower GA being related to both poorer cognitive outcomes and elevated affective and attention-deficit/hyperactivity problems. Global cognitive functioning did not independently predict aspects of behavioral outcomes. Findings demonstrate that, even in children born PT without severe perinatal and/or postnatal complications and receiving active perinatal care, a short gestation is an evident risk factor for long-term negative effects on mental health independent of cognitive functioning. Additional findings suggest that both reduced growth and lower parental educational level may contribute to increased risk for poorer cognitive and behavioral functioning in children born PT.
Assessment of Water and Nitrogen Use Efficiencies Through UAV-Based Multispectral Phenotyping in Winter Wheat

Unmanned aerial vehicle (UAV) based remote sensing is a promising approach for non-destructive and high-throughput assessment of crop water and nitrogen (N) efficiencies. In this study, UAV was used to evaluate two field trials using four water (T0 = 0 mm, T1 = 80 mm, T2 = 120 mm, and T3 = 160 mm), and four N (T0 = 0, T1 = 120 kg ha–1, T2 = 180 kg ha–1, and T3 = 240 kg ha–1) treatments, respectively, conducted on three wheat genotypes at two locations. Ground-based destructive data of water and N indictors such as biomass and N contents were also measured to validate the aerial surveillance results. Multispectral traits including red normalized difference vegetation index (RNDVI), green normalized difference vegetation index (GNDVI), normalized difference red-edge index (NDRE), red-edge chlorophyll index (RECI) and normalized green red difference index (NGRDI) were recorded using UAV as reliable replacement of destructive measurements by showing high r values up to 0.90. NGRDI was identified as the most efficient non-destructive indicator through strong prediction values ranged from R2 = 0.69 to 0.89 for water use efficiencies (WUE) calculated from biomass (WUE.BM), and R2 = 0.80 to 0.86 from grain yield (WUE.GY). RNDVI was better in predicting the phenotypic variations for N use efficiency calculated from nitrogen contents of plant samples (NUE.NC) with high R2 values ranging from 0.72 to 0.94, while NDRE was consistent in predicting both NUE.NC and NUE.GY by 0.73 to 0.84 with low root mean square errors. UAV-based remote sensing demonstrates that treatment T2 in both water 120 mm and N 180 kg ha–1 supply trials was most appropriate dosages for optimum uptake of water and N with high GY. Among three cultivars, Zhongmai 895 was highly efficient in WUE and NUE across the water and N treatments. Conclusively, UAV can be used to predict time-series WUE and NUE across the season for selection of elite genotypes, and to monitor crop efficiency under varying N and water dosages.