Miracle-dz/UniFAR-FTUs huggingface dataset:
Methodological challenges in translational drug response modeling in cancer: A systematic analysis with FORESEE

Translational models directly relating drug response specific processes that can be observed in vitro to their in vivo role in cancer patients constitute a crucial part of the development of personalized medication. Unfortunately, current studies often focus on the optimization of isolated model characteristics instead of examining the overall modeling workflow and the interplay of the individual model components. Moreover, they are often limited to specific data sets only. Therefore, they are often confined by the irreproducibility of the results and the non-transferability of the approaches into other contexts. In this study, we present a thorough investigation of translational models and their ability to predict the drug responses of cancer patients originating from diverse data sets using the R-package FORESEE. By systematically scanning the modeling space for optimal combinations of different model settings, we can determine models of extremely high predictivity and work out a few modeling guidelines that promote simplicity. Yet, we identify noise within the data, sample size effects, and drug unspecificity as factors that deteriorate the models’ robustness. Moreover, we show that cell line models of high accuracy do not necessarily excel in predicting drug response processes in patients. We therefore hope to motivate future research to consider in vivo aspects more carefully to ultimately generate deeper insights into applicable precision medicine.
MAP Train My Brain: Meditation Combined with Aerobic Exercise Reduces Stress and Rumination While Enhancing Quality of Life in Medical Students.

Medical students must commit a great deal of concentration and energy during their first 2 years of study, leaving minimal time for self-care. However, once they become physicians, they are in the position of instructing their patients to engage in self-care. Objectives: In this study, first- and second-year medical students participated in a combined mental and physical (MAP) training program with meditation and aerobic exercise that targeted brain health. Design: Each weekly session began with 30 min of instructional training that emphasized the benefit of the program for brain and body health, followed by 30 min of silent meditation, and ending with 30 min of aerobic exercise. Participants monitored their heart rate to achieve 60%-80% of their personal maximum. Participants engaged in one additional session of MAP training each week on their own. Location and Subjects: Sixty-one first- and second-year medical students were recruited to be participants from the Robert Wood Johnson Medical School (RWJMS) in Piscataway, NJ. Outcome measures: Participants completed questionnaires of depressive symptoms, perceived stress, ruminative thoughts, and quality of life, before and after the training approximately 8-9 weeks apart. Results: After 8 weeks of training and in contrast to students who did not participate, the medical students reported significantly fewer ruminations (-17%), including depressive (-16%) and brooding ruminations (-24%). Ruminations are repetitive thoughts that are typically negative in nature and associated with symptoms of depression. The medical students also reported greater quality of life at the end of training and less perceived stress. The majority (84%) would recommend these types of practices and this one in particular to their future patients. Previous studies have demonstrated that MAP training can reduce symptoms of depression in patients with major depressive disorder as well as trauma-related cognitions in those with post-traumatic stress disorder, while increasing oxygen consumption and synchronized brain activity during cognitive control procedures. Overall, MAP training offers a time-efficient and evidence-based means of maintaining mental and physical wellness for students during medical school and into their future, as well as their patients alike.
Facets and Defects in Perovskite Nanocrystals for Photocatalytic CO2 Reduction.

Light emitting lead halide perovskite nanocrystals are typically obtained in six faceted cube shape. However, for applications like catalysis, more active facets for adsorption/desorption of reactants/products and suppression of carrier recombination are essentially required. To meet these challenges, herein, CsPbBr3 perovskite nanocrystals in cube and faceted non-cube shapes were explored for photocatalytic reductions of CO2. Importantly, the halide deficient dim multifaceted non-cube emitters having less than 1% photoluminescence quantum yields showed superior catalytic activity than the bright halide rich cube nanocrystals. Beyond these, hexapod shaped nanocrystals were also explored and these remained in intermediate. With support of density functional theory, adsorption and desorption probability of reactants/products in different facets were also calculated and correlated with experimental findings. These results concluded that facets and defects of perovskite nanocrystals are equally important for carrying out catalytic reactions.
Rapid and repeated divergence of animal chemical signals in an island introduction experiment.

Studies of animal communication have documented myriad rapid, context-dependent changes in visual and acoustic signal design. In contrast, relatively little is known about the capacity of vertebrate chemical signals to rapidly respond, either plastically or deterministically, to changes in context. Four years following an experimental introduction of lizards to replicate experimental islets, we aimed to determine if chemical signal design of the experimental populations differed from that of the source population. In 2014, we translocated Podarcis erhardii lizards from a large, predator-rich island to each of five replicate predator-free islets. Mean population densities increased fivefold over the following 4 years and bite scars suggest significantly more intraspecific fighting among these experimental populations. In 2018, we analysed the chemical signal design of males in each of the experimental populations and compared it to the chemical signals of the source population. We found that males consistently presented a significantly more complex chemical signal compared to the source population. Moreover, their chemical signals were marked by high proportions of octadecanoic acid, oleic acid and α-tocopherol, the three compounds that are known to be associated with lizard territoriality and mate choice. Our island introduction experiment thus suggests that the chemical signal design of animals can shift rapidly and predictably in novel ecological contexts.
Armed against Unhappiness: Psychoanalytic Grammars in Buenos Aires.

Psychoanalysis has produced an ensemble of institutions, expertise, procedures, and practices for rendering the psychoanalytic subject legible and, through this, psychic life as an actionable site of intervention, dislocation, and struggle. This article examines how diverse psychoanalytic communities in Buenos Aires have produced unique grammars that influence how individuals articulate ideas about health and well-being. Descriptive, culturally specific, historically informed, and always provisional, this grammar is empirically grounded in lived experience. Through presenting several case studies, I flesh out how this grammar, as a deictic expression of/for the unconscious is deployed, reworked, and embodied in everyday interactions. I demonstrate how psychic life is enmeshed within social and political experience. In doing so, I consider how interpersonal, existential, environmental, social, and political contingencies shape divergent notions of well-being and structure desires of what it means to live "a good life. "
An unusual variant glycophorin expressing protease‐resistant M antigen encoded by the GYPB‐E(2‐4)‐B hybrid gene

MNS is a highly polymorphic blood group comprising 49 antigens recognized by International Society of Blood Transfusion, some of which may have been generated by genomic recombination among the closely linked genes GYPA, GYPB and GYPE. The GYPE gene has an almost identical sequence to GYPA*01 allele in exon 2 (99% homology), which accounts for M antigen. We investigated an unusual glycophorin molecule with protease‐resistant M antigen.
Meta‐analytic evidence for a joint neural mechanism underlying response inhibition and state anger

Although anger may weaken response inhibition (RI) by allowing outbursts to bypass deliberate processing, it is equally likely that RI deficits precipitate a state of anger (SA). In adolescents, for instance, anger occurs more frequently and often leads to escalating aggressive behaviors. Even though RI is considered a key component in explaining individual differences in SA expression, the neural overlap between SA and RI remains elusive. Here, we aimed to meta‐analytically revisit and update the neural correlates of motor RI, to determine a consistent neural architecture of SA, and to identify their joint neural network. Considering that inhibitory abilities follow a protracted maturation until early adulthood, we additionally computed RI meta‐analyses in youths and adults. Using activation likelihood estimation, we calculated twelve meta‐analyses across 157 RI and 39 SA experiments on healthy individuals. Consistent with previous findings, RI was associated with a broad frontoparietal network including the anterior insula/inferior frontal gyrus (aI/IFG), premotor and midcingulate cortices, extending into right temporoparietal areas. Youths showed convergent activity in right midcingulate and medial prefrontal areas, left aI/IFG, and the temporal poles. SA, on the other hand, reliably recruited the right aI/IFG and anterior cingulate cortex. Conjunction analyses between RI and SA yielded a single convergence cluster in the right aI/IFG. While frontoparietal networks and bilateral aI are ubiquitously recruited during RI, the right aI/IFG cluster likely represents a node in a dynamically‐adjusting monitoring network that integrates salient information thereby facilitating the execution of goal‐directed behaviors under highly unpredictable scenarios.
Infant behavioral inhibition predicts personality and social outcomes three decades later

Significance Children show different temperamental styles early in development. Whether temperament predicts who children become as adults and how early we can predict these outcomes have been long-standing questions of interest to the scientific and public community. The current study used rigorous methods to characterize an inhibited temperament by 14 mo of age in a cohort of infants and followed them for three decades. We provide the strongest and earliest evidence showing that infants with an inhibited temperament at 14 mo became introverted adults, with poorer functioning in some social and mental health domains. Also, brain activity underlying cognitive control in adolescence was associated with adult mental health. These findings highlight the lasting influence of early temperament on social-emotional development. Does infant temperament predict adult personality and life-course patterns? To date, there is scant evidence examining relations between child temperament and adult outcomes, and extant research has relied on limited methods for measuring temperament such as maternal report. This prospective longitudinal study followed a cohort of infants (n = 165) for three decades to examine whether infant behavioral inhibition, a temperament characterized by cautious and fearful behaviors to unfamiliar situations, shapes long-term personality, social relationships, vocational/education, and mental health outcomes in adulthood. At age 14 mo, behavioral inhibition was assessed using an observation paradigm. In adolescence (15 y; n = 115), error monitoring event-related potentials were measured in a flanker task. In adulthood (26 y; n = 109), personality, psychopathology, and sociodemographics were self-reported using questionnaires. We found that infants with higher levels of behavioral inhibition at 14 mo grew up to become more reserved and introverted adults (β = 0.34) with lower social functioning with friends and family (β = −0.23) at age 26. Infant behavioral inhibition was also a specific risk factor for adult internalizing (i.e., anxiety and depression, β = 0.20) psychopathology, rather than a transdiagnostic risk for general and externalizing psychopathology. We identified a neurophysiologic mechanism underlying risk and resilience for later psychopathology. Heightened error monitoring in adolescence moderated higher levels of adult internalizing psychopathology among behaviorally inhibited individuals. These findings suggest meaningful continuity between infant temperament and the development of adult personality. They provide the earliest evidence suggesting that the foundation of long-term well-being is rooted in individual differences in temperament observed in infancy.
Genome-wide binding analysis reveals that ANAC060 directly represses sugar-induced ABI5 transcription in Arabidopsis.

Plant sugar status acts as a signal affecting growth and development. The phenomenon by which high-levels of sugars inhibit seedling establishment has been widely used to gain insight into sugar-signaling pathways. Natural allelic variation has been identified at the ANAC060 locus. In the Columbia ecotype, a short ANAC060 protein without a transmembrane domain (TMD) is produced which is constitutively located to the nucleus causing sugar insensitivity when overexpressed. In this study, we generated a genome-wide DNA binding map of ANAC060 via chromatin immunoprecipitation sequencing (ChIP-seq) using transgenic lines that express a functional ANAC060-GFP fusion protein in an anac060 background. A total of 3282 genes associated with ANAC060 binding sites were identified. These genes were enriched in biotic and abiotic stress responses, and the G-box binding motif was highly enriched in ANAC060-bound genomic regions. Expression microarray analysis resulted in the identification of 8350 genes whose activities were altered in the anac060 mutant and upon sugar treatment. Cluster analysis revealed that ANAC060 attenuates sugar-regulated gene expression. Direct target genes of ANAC060 included equivalent numbers of genes that were up-regulated or down-regulated by ANAC060. The various functions of these target genes indicate that ANAC060 has several functions. Our results demonstrate that ANAC060 directly binds to the promoter of ABI5 and represses the sugar-induced transcription of ABI5. Genetic data indicate that ABI5 is epistatic to ANAC060 in both sugar and abscisic Acid (ABA) responses.
Chinese herbal medicine combination therapy for patients with steroid-dependent ulcerative colitis

Abstract Background: Ulcerative colitis (UC) is a chronic non-specific intestinal inflammatory disease characterized by continuous and diffuse inflammatory response of colonic mucosa. Steroid-dependent UC is an important type of UC. Chinese herbal medicine is widely used in treating steroid-dependent UC in China. However, there is no systematic review and meta-analysis to collate and evaluate the evidence of these studies. The purpose of this research is to provide evidence of the efficacy and safety of Chinese herbal medicine in treating steroid-dependent UC. Methods and analysis: Six databases, including 3 English databases and 3 Chinese databases will be searched. In addition, other grey literatures and ongoing studies will also be searched. Two researchers will independently select eligible studies by reading titles, abstracts and full texts according to the inclusion and exclusion criteria. Risk of bias assessment will be conducted by 2 independent reviewers using Cochrane risk-of-bias tool. The outcomes include steroid-free remission rate, Total clinical effective rate, Incidence of adverse events, Disease activity index (modified Mayo score), Results of enteroscopy (Baron score) and mucosa (geboes index score). Heterogeneity between studies will be assessed by Cochrane X2 and I2 tests. We will conduct subgroup analysis and meta-regression to explore the source of heterogeneity. We will also evaluate the stability of the results through sensitivity analysis and publication bias through funnel plot and Egger test. Results: The results will be published in peer-reviewed journals. Conclusion: Our meta-analysis and systematic evaluation results will confirm whether Chinese herbal medicine is effective in the treatment of steroid-dependent UC. It will provide more ideas for future research. OSF registration number: DOI: 10.17605/OSF.IO/YP79Z
Outcomes of immunomodulatory and biologic therapy in people living with HIV: a report from two academic hospitals.

OBJECTIVES Immunomodulatory drugs (IMDs) are crucial for treating autoimmune, inflammatory, and oncologic conditions. Data regarding the safety of IMDs in people living with HIV (PLWH) are limited. We describe outcomes in all PLWH prescribed these agents from 2000--2019 at two academic medical centers. DESIGN Retrospective cohort study. METHODS We systematically identified and reviewed charts of all PLWH receiving IMDs. We defined a treatment episode as an uninterrupted period on an IMD regimen. We quantified infections, blips (detectable viral load following an undetectable result), and virologic failure (progression from viral load <200 copies/ml to two consecutive values >200 copies/ml despite ART). RESULTS Seventy-seven patients contributed 110 treatment episodes. Rheumatologic comorbidities were the most frequent indication. The most common IMD classes were TNF inhibitors, antimetabolites, and checkpoint inhibitors. Ninety percent of treatment episodes involved concomitant ART. Median pretreatment CD4 T-cell count was 609 (IQR 375--861). Among 51 treatment episodes on ART with undetectable pretreatment plasma HIV RNA, HIV became detectable within 1 year in 21 cases (41.2%); there were no instances of virologic failure. Compared with other agents, treatment episodes involving checkpoint inhibitors were more likely to involve a blip (77.8 vs. 33.3%, P = 0.015). Thirteen treatment episodes (11.8%) were associated with concomitant infection; none was attributed to IMDs by the treating clinician. CONCLUSION PLWH treated with IMDs should be monitored carefully for virologic blips and incident infections. Checkpoint inhibitors may be associated with a higher rate of viral blips, although the clinical significance is unclear.
Galectin-3 mediates high-glucose-induced cardiomyocyte injury by NADPH oxidase/reactive oxygen species pathway.

Galectin-3 is a member of the β-galactoside-binding lectin family taken part in the regulation of inflammation, angiogenesis, and fibrosis. This study was designed to study the improved effect of galectin-3 inhibition on diabetic cardiomyopathy (DCM). Sprague-Dawley rats were randomized into the control, DCM, and DCM + modified citrus pectin (MCP, a galectin-3 pharmacological inhibitor) groups. After 8 weeks, streptozotocin (STZ)-induced DCM led to high blood glucose level, oxidative stress, cardiac injury, and dysfunction, accompanied by suppressed body weight. On the contrary, MCP (100 mg/kg/day) administration improved body weight and blood glucose level and attenuated cardiac injury and dysfunction in DCM rats. Additionally, MCP attenuated pathological changes in plasma and myocardial tissue markers of oxidative stress, such as hydrogen peroxide and malonydialdehyde, although it did not change superoxide dismutase (SOD) activities, which were decreased in the DCM group. The levels of oxidative stress-associated proteins evaluated by Western blot, such as p67phox and NADPH oxidase (NOX) 4, were obviously increased in the DCM group, while it was reversed by MCP treatment. Therefore, galectin-3 mediated high-glucose-induced cardiomyocyte injury, and galectin-3 inhibition attenuated DCM by suppressing NADPH oxidase. These findings suggested that galectin-3 could be a potential target for treatment of patients with DCM.
Development of an annelid-like peristaltic crawling soft robot using dielectric elastomer actuators

The annelid, which consists of several identical segments, exploits its soft structures to move effectively in complex natural environments. Elongation and shortening of different segments produce a reverse peristaltic wave while retractable setae generate a variable friction, enabling bidirectional crawling locomotion. Although several designs have applied soft technologies towards the construction of annelid-like robots, these robots do not exhibit the homonymous segmentation, reverse peristaltic wave and variable friction. This paper reports the development of an annelid-like soft robot based on an improved dielectric elastomer (DE) minimum energy structure actuator to have these annelidan features. Each biomimetic segment of the robot is supported by a polyethylene terephthalate (PET) frame adhered to the DE actuator. The DE actuator induces segment elongation or shortening, which causes silica gel pads attached to the PET frame to contact or separate from the ground, producing a variable friction. The designed robot, whose identical segments conform to the homonymous segmentation, achieves forward or backward movement via the cooperative efforts of all the biomimetic segments. This cooperative movement, which produces the reverse peristaltic wave, strongly resembles that of natural annelidan locomotion. In addition, the kinematic analysis of the robot is investigated. Experimental results confirm that the designed robot is capable of bidirectional and rapid locomotion. The robot can achieve a maximum velocity of 11.5 mm s−1 and a maximum velocity/mass ratio of 86.25 mm (min−1 g−1). Compared to other existing annelid-like soft robots, this designed robot exhibits a superior average velocity, velocity/length ratio, body length/cycle, and velocity/mass ratio, and its performance affords the best approximation to that of the natural annelid.
Cloning and sequencing of Candidatus liberibacter asiaticus isolated from citrus trees in Malaysia.

Candidatus liberibacter asiaticus, a causal agent of huanglongbing (HLB) disease of citrus in Malaysia, was detected in infected leaf samples collected from citrus growing areas in Selangor and Terangganu. The HLB bacterium was cloned and sequenced. The nucleotide sequences were 1324 and 1337 bp for GFB (greening fastidious bacterium) -T and-S isolate, respectively including the upstream and downstream nucleotides. It was confirmed that both sequences were full of 16S rDNA gene of C. liberibacter asiaticus. The sequences of 16S rDNA gene of Malaysian isolates are identical to each other, and had close relationship with isolates or strains from China. However, it showed slight difference from those African and American species.
On the evolution of the quality of macromolecular models in the PDB

Crystallographic models of biological macromolecules have been ranked using the quality criteria associated with them in the Protein Data Bank (PDB). The outcomes of this quality analysis have been correlated with time and with the journals that published papers based on those models. The results show that the overall quality of PDB structures has substantially improved over the last ten years, but this period of progress was preceded by several years of stagnation or even depression. Moreover, the study shows that the historically observed negative correlation between journal impact and the quality of structural models presented therein seems to disappear as time progresses.