Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of Primary Systemic Therapy on PD-1, PD-L1, and PD-L2 mRNA Expression in Advanced Breast Cancer

Objective: The association between PD-1, PD-L1, and PD-L2 expression and prognosis has been extensively studied in various cancers but remained controversial in breast cancer. Besides, little is known about the prognostic value of PD-1, PD-L1, and PD-L2 upregulation or downregulation following systemic therapy (chemotherapy and hormonal therapy) in breast cancer. Therefore, we aim to investigate the change of PD-1, PD-L1, and PD-L2 expression in mRNA level after primary systemic therapy in breast cancer patients and its clinical implications. Methods: Expression of PD-1, PD-L1, and PD-L2 mRNA were measured before-after chemotherapy and hormonal therapy with real-time PCR in 80 advanced breast cancer patients. The correlation between alteration of PD-1, PD-L1, and PD-L2 expression and clinicopathological characteristics as well as overall survival was also statistically analyzed. Results: Chemotherapy and hormonal therapy altered PD-1, PD-L1, and PD-L2 expression in breast cancer with most patients have an increase expression. As much as 57.1%, 62.9% and 60% patients have an increase PD-1, PD-L1, and PD-L2 expression after chemotherapy, while 60%, 60%, and 64% patients have an increase PD-1, PD-L1, and PD-L2 expression after hormonal therapy. Alteration of PD-1, PD-L1, and PD-L2 expression was not correlated with all clinicopathological characteristics. Increase in PD-1, PD-L1, and PD-L2 expression was significantly associated with better OS (p=0.031, p=0.019, and p=0.019 for PD-1, PD-L1, and PD-L2, respectively), which remained significant in multivariate analysis including age, stage, primary systemic therapy, histology grade, subtype and primary tumor histology (HR PD-1 0.5 (95% CI 0.28-0.88) p=0.031; HR PD-L1 0.43 (95% CI 0.24-0.8) p=0.019; HR PD-L2 (95% CI 0.24-0.87) p=0.019). Conclusion: Expression of PD-1, PD-L1, and PD-L2 in breast cancer patients is mostly enhanced after chemotherapy and hormonal therapy, and the enhancement is associated with good OS. This result revealed the potential of measuring PD-1, PD-L1, and PD-L2 mRNA expression in predicting clinical outcome.
COVID-19 state anxiety of older adults: effects of defensive information processes

ABSTRACT Background and Objectives To explore coping processes used by adults aged 60 and above (defined as high age-related risk group) in reaction to the COVID-19 threat, and the associations between these processes and state anxiety. Design and Methods A cross-sectional study with 498 respondents of an online survey, 72 (15%) in the high age-related risk group. Questionnaires measured: background variables, state anxiety, and COVID-19 related perceptions. Results The high age-related risk group perceived the coronavirus as more severe, their belongingness to a risk group as higher, and the behavioral recommendations as more effective compared to the low age-related risk group. The part of perceived vulnerability that is not explained by belonging to an age-related risk group (defined as residual perceived vulnerability) was lower in the high age-related risk group. Mediation analysis indicated that the high (compared to the low) age-related risk group had lower anxiety levels, and that this effect was mediated by lower residual perceived vulnerability and higher perceived disease severity levels. Conclusions The higher age-related risk group maintains a relatively moderate level of anxiety without denying their belonging to a high risk group. This can be explained by defensive processing of COVID-19 related information and by developmental processes.
Transition to psychosis in randomized clinical trials of individuals at clinical high risk of psychosis compared to observational cohorts: a systematic review and meta-analysis

Abstract Background Individuals at clinical high risk of psychosis (CHR-P) recruited in randomized clinical trials (RCTs) and observational cohorts may display a different enrichment and hence risk of transition to psychosis. No meta-analysis has ever addressed this issue. Methods “Preferred Reporting Items for Systematic reviews and Meta-Analyses” (PRISMA) and “Meta-analysis Of Observational Studies in Epidemiology” (MOOSE)–compliant meta-analysis. PubMed and Web of Science were searched until November 2020 (PROSPERO:CRD42021229223). We included nonoverlapping longitudinal studies (RCTs-control condition and observational cohorts) reporting the transition to psychosis in CHR-P individuals. The primary effect size measure was the cumulative risk of transition at 0.5, 1, and 2 years follow-up in RCTs compared to observational cohorts. Random effects meta-analyses, heterogeneity assessment, quality assessment, and meta-regressions were conducted. Results Ninety-four independent studies (24 RCTs, 70 observational cohorts) and 9,243 individuals (mean age = 20.1 ± 3.0 years; 43.7% females) were included. The meta-analytical risk of transitioning to psychosis from a CHR-P stage was 0.091 (95% confidence intervals [CI] = 0.068–0.121) at 0.5 years, 0.140 (95% CI = 0.101–0.191) at 1 year and 0.165 (95% CI = 0.097–0.267) at 2 years follow-up in RCTs, and 0.081 (95% CI = 0.067–0.099) at 0.5 years, 0.138 (95% CI = 0.114–0.167) at 1 year, and 0.174 (95% CI = 0.156–0.193) at 2 years follow-up in observational cohorts. There were no between-group differences in transition risks (p > 0.05). The proportion of CHR-P individuals with substance use disorders (excluding alcohol and cannabis) was higher in observational cohorts (16.8, 95% CI = 13.3–21.0%) than in RCTs (3.4, 95% CI = 0.8–12.7%; p = 0.018). Conclusions There is no meta-analytic evidence supporting sampling biases in RCTs of CHR-P individuals. Further RCTs are needed to detect effective interventions to prevent psychosis in this at-risk group.
Oxygenation, Life, and the Planetary System during Earth's Middle History: An Overview

The long history of life on Earth has unfolded as a cause-and-effect relationship with the evolving amount of oxygen (O2) in the oceans and atmosphere. Oxygen deficiency characterized our planet's first 2 billion years, yet evidence for biological O2 production and local enrichments in the surface ocean appear long before the first accumulations of O2 in the atmosphere roughly 2.4 to 2.3 billion years ago. Much has been written about this fundamental transition and the related balance between biological O2 production and sinks coupled to deep Earth processes that could buffer against the accumulation of biogenic O2. However, the relationship between complex life (eukaryotes, including animals) and later oxygenation is less clear. Some data suggest O2 was higher but still mostly low for another billion and a half years before increasing again around 800 million years ago, potentially setting a challenging course for complex life during its initial development and ecological expansion. The apparent rise in O2 around 800 million years ago is coincident with major developments in complex life. Multiple geochemical and paleontological records point to a major biogeochemical transition at that time, but whether rising and still dynamic biospheric oxygen triggered or merely followed from innovations in eukaryotic ecology, including the emergence of animals, is still debated. This paper focuses on the geochemical records of Earth's middle history, roughly 1.8 to 0.5 billion years ago, as a backdrop for exploring possible cause-and-effect relationships with biological evolution and the primary controls that may have set its pace, including solid Earth/tectonic processes, nutrient limitation, and their possible linkages. A richer mechanistic understanding of the interplay between coevolving life and Earth surface environments can provide a template for understanding and remotely searching for sustained habitability and even life on distant exoplanets.
Fifteen‐Year Trends in Incidence of Cardiogenic Shock Hospitalization and In‐Hospital Mortality in the United States

Background There is a lack of contemporary data on cardiogenic shock (CS) in‐hospital mortality trends. Methods and Results Patients with CS admitted January 1, 2004 to December 31, 2018, were identified from the US National Inpatient Sample. We reported the crude and adjusted trends of in‐hospital mortality among the overall population and selected subgroups. Among a total of 563 949 644 hospitalizations during the period from January 1, 2004, to December 30, 2018, 1 254 358 (0.2%) were attributed to CS. There has been a steady increase in hospitalizations attributed to CS from 122 per 100 000 hospitalizations in 2004 to 408 per 100 000 hospitalizations in 2018 (P trend<0.001). This was associated with a steady decline in the adjusted trends of in‐hospital mortality during the study period in the overall population (from 49% in 2004 to 37% in 2018; P trend<0.001), among patients with acute myocardial infarction CS (from 43% in 2004 to 34% in 2018; P trend<0.001), and among patients with non–acute myocardial infarction CS (from 52% in 2004 to 37% in 2018; P trend<0.001). Consistent trends of reduced mortality were seen among women, men, different racial/ethnic groups, different US regions, and different hospital sizes, regardless of the hospital teaching status. Conclusions Hospitalizations attributed to CS have tripled in the period from January 2004 to December 2018. However, there has been a slow decline in CS in‐hospital mortality during the studied period. Further studies are necessary to determine if the recent adoption of treatment algorithms in treating patients with CS will further impact in‐hospital mortality.
Negotiating Time and Space When Working From Home: Experiences During COVID-19

Stay-at-home mandates following the COVID-19 pandemic increased work from home (WFH). While WFH offers many benefits, navigating work in nontraditional contexts can be a challenge. The objective of this study was to explore the benefits and challenges of WFH during COVID-19 to identify supports and resources necessary. Comments from two free-response questions on a survey regarding experiences of WFH (N = 648, N = 366) were analyzed using inductive qualitative content analysis. Four themes emerged: time use, considerations of working in the home space, intersections between work-life and home-life, and temporality of WFH as situated within a pandemic. Across all themes were concerns related to participation in both work and home roles, work performance, and well-being. Findings highlight the importance of support during times of disruption of occupational patterns, roles, and routines. Despite challenges, many individuals hoped to continue WFH. Organizations should consider the complex intersections of work-life and home-life to develop supportive policies and resources.
First Report of a Multidrug-Resistant ST58 Escherichia coli Harboring Extended-Spectrum Beta-Lactamase of the CTX-M-1 Class in a Fecal Sample of a Captive Baird's Tapir (Tapirus bairdii) in Costa Rica, Central America.

Objective: This study's main objective was to analyze the antibiotic susceptibility profile of Escherichia coli isolates obtained from a fecal sample of a captive Baird's tapir (Tapirus bairdii) in Costa Rica. Materials and Methods: The fecal sample was collected inside the enclosure on March 3, 2017, right after the animal defecated. Samples were cultured on MacConkey agar plates nonsupplemented and supplemented with 2 μg/mL of cefotaxime. Bacterial identification and antibiotic susceptibility were performed with the Vitek 2 Compact System and the Kirby Bauer disk diffusion method, respectively. Polymerase chain reaction amplification was performed to detect blaCTX-M beta-lactamase genes. Resistant isolates were subjected to whole-genome sequencing (WGS). Results: After evaluating several antibiotic classes, a multidrug-resistant E. coli strain with extended-spectrum beta-lactamase phenotype was isolated. Resistance to cefotaxime, cefepime, ampicillin, ampicillin/sulbactam, and tetracycline was detected. WGS analysis showed the presence of blaCTX-M-1, blaTEM-1B, and tet(B) genes. The presence of IncN plasmids and Col156 was also detected. Conclusion: Our findings are according with the notion that animals' high density enhances the spread of resistant determinants in a captive environment in a limited space, where the likelihood of direct or indirect contact with other animals and humans is more frequent.
Leveraging a preexisting global infectious disease network for local decision-making during a pandemic

Abstract Emerging infectious disease epidemics require a rapid response from health systems; however, evidence-based consensus guidelines are generally absent early in the course of events. Formed in 2017 by five high-level isolation units spanning three continents, the experience of the Global Infectious Disease Preparedness Network (GIDPN) early in the course of COVID-19 provides a model for accelerating best practice development and improving decision-making in health emergencies. The network served as a platform for real-time, open and transparent information-sharing during unknowns of an active outbreak by clinicians caring for patients, by researchers conducting clinical trials and transmission and infection prevention studies, and by teams advising local and national policymakers. Shared knowledge led to earlier adoption of some treatment modalities as compared to most peer institutions and to implementation of protocols prior to incorporation into national guidelines. GIDPN and similar networks are integral in enhancing preparedness for and response to future epidemics/pandemics.
The association between personalities, alternative breeding strategies and reproductive success in dunnocks

Although consistent between‐individual differences in behaviour (i.e. animal personality) are ubiquitous in natural populations, relatively few studies have examined how personalities influence the formation of social relationships. Yet, behavioural characteristics of both sexes might be key when it comes to pair‐bond formation, and cooperation with partners to successfully rear offspring. We here use a wild population of dunnocks (Prunella modularis) to first investigate whether individuals mate nonrandomly (i.e. assortative mating) with regard to four behavioural traits—flight‐initiation distance (FID), provisioning, activity and vigilance—that differ in repeatability and have previously been associated with mating patterns and fitness in other species. Second, we test whether an individual's FID is associated with variability in the dunnocks' mating system (i.e. monogamous pairs vs. polygamous groups). Finally, we determine whether FID and provisioning of males and females associate with their reproductive success. We found no statistical support for assortative mating in FID between males and females. Interestingly, in polygamous groups, co‐breeding males differed in their FIDs with dominant alpha males having significantly shorter FIDs compared with subordinate beta‐males. Moreover, there was evidence for assortative mating in provisioning for alpha males and females in polygamous groups. We also found that male provisioning influenced reproductive success of both sexes, whereas female provisioning rates only positively correlated with her own but not their partner(s) reproductive output. Our results suggest that personality differences may have important implications for social relationships, the emergence of different mating patterns and ultimately reproductive success within populations.
A chondroitin sulfate proteoglycan 4-specific monoclonal antibody inhibits melanoma cell invasion in a spheroid model

The overexpression of chondroitin sulfate proteoglycan 4 (CSPG4) is associated with several tumor types, including malignant melanoma, squamous cell carcinoma, triple-negative breast carcinoma, oligodendrocytomas or gliomas. Due to its restricted distribution in normal tissues, CSPG4 has been considered a potential target for several antitumor approaches, including monoclonal antibody (mAb) therapies. The aim of the present study was to characterize the impact of the CSPG4-specific mAb clone 9.2. 27 on its own or in combination with the commonly used BRAF-selective inhibitor, PLX4032, on different functions of melanoma cells to assess the potential synergistic effects. The BRAF V600-mutant human melanoma cell lines, M14 (CSPG4-negative) and WM164 (CSPG4-positive), were exposed to the CSPG4-specific 9.2. 27 mAb and/or PLX4032. Cell viability and colony formation capacity were evaluated. A 3D-cell culture spheroid model was used to assess the invasive properties of the treated cells. In addition, flow cytometric analysis of apoptosis and cell cycle analyses were performed. Incubation of the WM164 cell line with CSPG4-specific 9.2. 27 mAb decreased viability, colony formation ability and the invasive capacity of CSPG4-positive tumor cells, which was not the case for the CSPG4-negative M14 cell line. Combined treatment of the WM164 cells with 9.2. 27 mAb plus PLX4032 did not exert any significant additional effect in comparison to treatment with PLX4032 alone in the clonogenic and invasion assays. M14 cell cycle distribution was not influenced by the CSPG4-specific 9.2. 27 mAb. By contrast, the exposure of WM164 cells to the mAb resulted in an arrest of the cells in the S phase. Moreover, combined treatment of the WM164 cells led to a significantly increased accumulation of cells in the subG1 phase, combined with a decrease of cells in the G2/M phase. On the whole, findings of the present study indicate that the CSPG4-specific 9.2. 27 mAb exerts an anti-invasive effect on CSPG4-positive melanoma spheroids, which is not enhanced by BRAF inhibition. These findings provide the basis for further investigations on the effects of anti-CSPG4-based treatments of CSPG4-positive tumors.
Age‐related functional connectivity along the hippocampal longitudinal axis

Accumulated evidence points toward a long‐axis functional division of the hippocampus, with its anterior part primarily associated with emotional processes and the posterior with navigation and cognition. It is yet unclear, however, how functional connectivity between areas along the hippocampal longitudinal axis and other brain regions differ, and how they are affected by age. Applying an anatomically driven general linear model‐based functional connectivity analysis on a large database of resting‐state fMRI data, we demonstrate that independent of age, the posterior hippocampus is functionally connected primarily with sensory and motor areas, the middle hippocampus with the default mode network, and the anterior with limbic and prefrontal regions. Along with an age‐related disintegration of intra‐hippocampal BOLD signal uniformity, the middle and posterior sub‐regions exhibit mostly decreases in their functional connectivity with cortical regions, whereas the anterior hippocampus and ventral striatum appear to become more synchronized with age. These findings indicate that long‐axis hippocampal areas are tuned to particular functional networks, which do not age in a unified manner.
A preliminary analysis of physical therapist agreement regarding the perceived impairments in cases of runners with knee pain

ABSTRACT Background There is a scarcity of evidence describing how physical therapists use data from clinical examinations to inform the treatment of runners with knee pain. Objective Our purpose was to examine the between physical therapist agreement on the selection of perceived impairments in runners with knee pain. Methods Twelve physical therapists reviewed two cases of runners with knee pain. The cases included clinical subjective information, objective data, and review of videos of each participant running. Each rater selected up to three perceived impairments (from a list of eight) that each physical therapist would address at the next physical therapy session. Percent agreement was calculated to determine the between rater agreement on each individual perceived impairment selection and Fleiss Kappa was calculated for each unique combination of three perceived impairments per case. Results Twelve raters with 51 (18–156) months of clinical experience participated. Percent agreement ranged from 8%-100% for both cases for individual impairments. When assessing the unique combination of three impairments selected, inter-rater agreement was less than what is expected due to chance alone (κ = −0.09, p = .92; κ = −0.09, p = .98) for both cases. Conclusion The 12 physical therapists demonstrated poor to excellent levels of agreement when selecting an individual perceived impairment. Agreement was worse than chance when selecting a combination of three unique impairments.
Ras/ERK and PI3K/AKT signaling differentially regulate oncogenic ERG mediated transcription in prostate cells

The TMPRSS2/ERG gene rearrangement occurs in 50% of prostate tumors and results in expression of the transcription factor ERG, which is normally silent in prostate cells. ERG expression promotes prostate tumor formation and luminal epithelial cell fates when combined with PI3K/AKT pathway activation, however the mechanism of synergy is not known. In contrast to luminal fates, expression of ERG alone in immortalized normal prostate epithelial cells promotes cell migration and epithelial to mesenchymal transition (EMT). Migration requires ERG serine 96 phosphorylation via endogenous Ras/ERK signaling. We found that a phosphomimetic mutant, S96E ERG, drove tumor formation and clonogenic survival without activated AKT. S96 was only phosphorylated on nuclear ERG, and differential recruitment of ERK to a subset of ERG-bound chromatin associated with ERG-activated, but not ERG-repressed genes. S96E did not alter ERG genomic binding, but caused a loss of ERG-mediated repression, EZH2 binding and H3K27 methylation. In contrast, AKT activation altered the ERG cistrome and promoted expression of luminal cell fate genes. These data suggest that, depending on AKT status, ERG can promote either luminal or EMT transcription programs, but ERG can promote tumorigenesis independent of these cell fates and tumorigenesis requires only the transcriptional activation function.
Chronic effects of flywheel training on physical capacities in soccer players: a systematic review

ABSTRACT The aims of the current systematic review were to evaluate the current literature surrounding the chronic effect of flywheel training on the physical capacities of soccer players, and to identify areas for future research to establish guidelines for its use. Studies were identified following a search of electronic databases (PubMed and SPORTDiscus) in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA). Eleven studies met the inclusion criteria and were included. The methodological quality of the included studies ranged between 10 and 18 with an average score of 15 points using the PEDro scale. The training duration ranged from 6 weeks to 27 weeks, with volume ranging from 1 to 6 sets and 6 to 10 repetitions, and frequency from 1 to 2 times a week. This systematic review reported that a diverse range of flywheel training interventions can effectively improve strength, power, jump, and changes of direction in male soccer players of varying levels. Flywheel training interventions improve the physical capacities of soccer players of varying levels. Nonetheless, the current literature suggests contrasting evidence regarding flywheel training induced changes in sprint speed and acceleration capacity of soccer players.