Miracle-dz/UniFAR-FTUs huggingface dataset:
Investigating differential abundance methods in microbiome data: A benchmark study

The development of increasingly efficient and cost-effective high throughput DNA sequencing techniques has enhanced the possibility of studying complex microbial systems. Recently, researchers have shown great interest in studying the microorganisms that characterise different ecological niches. Differential abundance analysis aims to find the differences in the abundance of each taxa between two classes of subjects or samples, assigning a significance value to each comparison. Several bioinformatic methods have been specifically developed, taking into account the challenges of microbiome data, such as sparsity, the different sequencing depth constraint between samples and compositionality. Differential abundance analysis has led to important conclusions in different fields, from health to the environment. However, the lack of a known biological truth makes it difficult to validate the results obtained. In this work we exploit metaSPARSim, a microbial sequencing count data simulator, to simulate data with differential abundance features between experimental groups. We perform a complete comparison of recently developed and established methods on a common benchmark with great effort to the reliability of both the simulated scenarios and the evaluation metrics. The performance overview includes the investigation of numerous scenarios, studying the effect on methods’ results on the main covariates such as sample size, percentage of differentially abundant features, sequencing depth, feature variability, normalisation approach and ecological niches. Mainly, we find that methods show a good control of the type I error and, generally, also of the false discovery rate at high sample size, while recall seem to depend on the dataset and sample size.
Yield of conilon coffee using the programmed pruning cycle and different cultivation densities

Determining the correct population of plants and number of orthotropic stems to be kept per area, along with optimal pruning management, is very important for crops of Coffea canephora. The aim of this work was to improve conilon coffee cropping management, evaluating the influence of the programmed pruning cycle with different combinations of spacing and numbers of orthotropic stems per plant on crop yield. Two experiments were carried out: one with smaller spacing and lower numbers of stems per plant, and another with larger spacing and higher numbers of stems per plant. Both assays followed a triple factorial scheme 2 x 3 x 4 (2 spacing x 3 numbers of stems per plant x 4 harvests) in a random block statistical design, using four replications and 11 plants pen plot. The results show that a reduction in spacing associated with an increase in number of stems per plant has a positive effect on the conilon coffee yield.
Factors influencing COVID-19 vaccine decision-making among hesitant adopters in the United States

ABSTRACT Increasing COVID-19 vaccine uptake is crucial to managing the endemic. In this qualitative study, we examine factors influencing the decision-making process of COVID-19 hesitant adopters – those who reported some level of hesitancy and are vaccinated. Using interviews with 49 participants, we documented multiple factors influencing the decision-making process to get the COVID-19 vaccine among a racially and ethnically diverse sample of hesitant adopters in the US. Participants described influences related to sociocultural context and personal and group influences, which affected their decision to get the COVID-19 vaccine despite being hesitant. We find politics, culture, healthcare professionals, employment, vaccine attitudes and beliefs, social networks, and the media influence the decision to get vaccinated. Our findings provide nuanced and in-depth information in their own words. This study expands on prior literature on COVID-19 vaccine hesitancy, especially among hesitant adopters. These findings can inform future interventions and research targeting vaccine-hesitant populations to increase vaccine uptake.
Enhancer Function and Evolutionary Roles of Human Accelerated Regions.

Human accelerated regions (HARs) are the fastest-evolving sequences in the human genome. When HARs were discovered in 2006, their function was mysterious due to scant annotation of the noncoding genome. Diverse technologies, from transgenic animals to machine learning, have consistently shown that HARs function as gene regulatory enhancers with significant enrichment in neurodevelopment. It is now possible to quantitatively measure the enhancer activity of thousands of HARs in parallel and model how each nucleotide contributes to gene expression. These strategies have revealed that many human HAR sequences function differently than their chimpanzee orthologs, though individual nucleotide changes in the same HAR may have opposite effects, consistent with compensatory substitutions. To fully evaluate the role of HARs in human evolution, it will be necessary to experimentally and computationally dissect them across more cell types and developmental stages. Expected final online publication date for the Annual Review of Genetics, Volume 56 is November 2022. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Physiotherapy practice for hospitalized patients with COVID-19

ABSTRACT Objective: To identify the indications for physiotherapy and to evaluate physiotherapy practices in patients with COVID-19 admitted to the ICU (on mechanical ventilation) or to the ward (spontaneously breathing). Methods: An online, 50-item survey was completed by physiotherapists who had been treating hospitalized patients with COVID-19 in Brazil. Results: Of the 644 physiotherapists who initiated the survey, 488 (76%) completed it. The main reasons for indications for physiotherapy in both settings reported as “very frequently” and “frequently” both in the ICU and the ward by most respondents were oxygenation improvement (> 95%) and prevention of general complications (> 83%). Physical deconditioning was considered an infrequent indication. When compared with mobilization strategies, the use of respiratory interventions showed great variability in both work settings, and techniques considered effective were underutilized. The most frequently used respiratory techniques in the ICU were positioning (86%), alveolar recruitment (73%), and hard/brief expiratory rib cage compression (46%), whereas those in the ward were active prone positioning (90%), breathing exercises (88%), and directed/assisted cough (75%). The mobilization interventions reported by more than 75% of the respondents were sitting on the edge of the bed, active and resistive range of motion exercises, standing, ambulation, and stepping in place. Conclusions: The least common reason for indications for physiotherapy was avoidance of deconditioning, whereas oxygenation improvement was the most frequent one. Great variability in respiratory interventions was observed when compared with mobilization therapies, and there is a clear need to standardize respiratory physiotherapy treatment for hospitalized patients with COVID-19.
Role of Excessive Weight Gain During Gestation in the Risk of ADHD in Offspring of Women With Gestational Diabetes.

CONTEXT Although attention-deficit/hyperactivity disorder (ADHD) has been associated with gestational diabetes mellitus (GDM) and maternal obesity, excessive weight gain (EWG) during pregnancy has scarcely been evaluated. OBJECTIVE This study aimed to assess the joint effect of maternal weight and EWG on the risk of ADHD in offspring of GDM pregnancies. METHODS In this cohort study of singleton births >22 weeks of gestation of women with GDM between 1991 and 2008, gestational weight gain above the National Academy of Medicine (NAM) recommendations was classified into EWG. Cox-regression models estimated the effect of maternal pregestational weight and EWG on the risk of ADHD (identified from medical records), adjusted for pregnancy outcomes and GDM-related variables. RESULTS Of 1036 children who were included, with a median follow-up of 17.7 years, 135 (13%) were diagnosed with ADHD. ADHD rates according to pregestational maternal weight were 1/14 (7.1%) for underweight, 62/546 (11.4%) for normal weight, 40/281 (14.2%) for overweight, and 32/195 (16.4%) for obesity. Only maternal obesity was independently associated with ADHD (HRadjusted 1.66 [95% CI, 1.07-2.60]), but not maternal overweight or EWG. On evaluating the joint contribution of maternal weight and EWG, maternal obesity with EWG was associated with the highest risk of ADHD (vs normal weight without EWG; HRadjusted 2.13 [95% CI, 1.14-4.01]). Pregestational obesity without EWG was no longer associated (HRadjusted 1.36 [95% CI, 0.78-2.36]). CONCLUSION Among GDM pregnancies, pregestational obesity was associated with a higher risk of ADHD in offspring. Nonetheless, when gestational weight gain was taken into account, only the joint association of obesity and EWG remained significant.
Comparison of the tumor immune microenvironment phenotypes in different breast cancers after neoadjuvant therapy

Neoadjuvant therapy (NAT) treats early‐stage breast cancers, especially triple‐negative breast cancers (TNBCs). NAT improves pathological complete response (pCR) rates for different breast cancer patients. Recently, immune checkpoint inhibitors that target programmed death 1 (PD‐1) or programmed death ligand 1 (PD‐L1) in combination with NAT have shown antitumor activity in patients with early breast cancer. However, the tumor immune microenvironment (TME) in different subtypes of breast cancers, like TNBC, hormone receptor‐positive (HR+), and human epidermal growth factor receptor 2 amplified (HER2+) and its changes by NAT remain to be fully characterized. We analyzed pre‐NAT tumor biopsies from TNBC (n = 27), HR+ (n = 24), and HER2+ (n = 30) breast cancer patients who received NAT, followed by surgery. The different immune makers (PD‐1, PD‐L1, CD3, and CD8) of tumor‐infiltrating lymphocytes (TILs) were identified with immunofluorescence‐based microenvironment analysis. TILs within cancer parenchyma (iTILs) and in cancer stroma (sTILs) were counted separately. We found that PD‐L1+ cells in tumor and stroma were significantly higher in TNBC patients than in others. PD‐L1+ sTILs were significantly higher in pCR than in non‐pCR patients of all the subtypes. The infiltration scores of B‐cell memory, T‐cell CD4+ memory activated, T‐cell follicular helper, and Macrophage M0 and M1 were relatively higher in TNBC patients, indicating immunoreactive TME in TNBC. Analysis of TCGA‐BRCA RNA‐seq indicated that PD‐L1 was highly expressed in TNBC patients compared with HR+ and HER2+ patients. Higher PD‐L1 expression in TNBC patients was associated with significantly longer overall survival (OS). Our results demonstrated that PD‐L1 expression level of iTILs and sTILs is highest in TNBC among breast cancers. TNBC patients had significantly different immunoreactive TME compared with HR+ and HER2+ patients, suggesting potentially favorable outcomes for immunotherapy in these patients. Also, PD‐L1+ could be a powerful predictor of pCR in TNBC patients after NAT.
Coevolution of the Ess1-CTD axis in polar fungi suggests a role for phase separation in cold tolerance

Most of the world’s biodiversity lives in cold (−2° to 4°C) and hypersaline environments. To understand how cells adapt to such conditions, we isolated two key components of the transcription machinery from fungal species that live in extreme polar environments: the Ess1 prolyl isomerase and its target, the carboxy-terminal domain (CTD) of RNA polymerase II. Polar Ess1 enzymes are conserved and functional in the model yeast, Saccharomyces cerevisiae. By contrast, polar CTDs diverge from the consensus (YSPTSPS)26 and are not fully functional in S. cerevisiae. These CTDs retain the critical Ess1 Ser-Pro target motifs, but substitutions at Y1, T4, and S7 profoundly affected their ability to undergo phase separation in vitro and localize in vivo. We propose that environmentally tuned phase separation by the CTD and other intrinsically disordered regions plays an adaptive role in cold tolerance by concentrating enzymes and substrates to overcome energetic barriers to metabolic activity.
Suspected chlamydial foetal loss highlights the need for standardised on‐farm protocols

Chlamydia psittaci is a recognised cause of late‐term equine foetal loss and poses a zoonotic risk in Australia. However, a management strategy is lacking to protect at‐risk humans handling infected aborted material and pregnant mares. This study proposes a protocol for approaching C. psittaci foetal loss after investigating four foetal losses that occurred on a horse stud in the Hunter Valley, Australia in 2021. Swabs from the foetal loss cases (n = 4), close contact mares (n = 59), and foals of the close contact mares (n = 33) were collected and tested for C. psittaci using both isothermal points of care and quantitative polymerase chain reaction (qPCR) laboratory‐based testing. Genotyping was performed utilising C. psittaci multilocus sequence typing and ompA sequencing from C. psittaci positive pooled foetal and placental (n = 3) DNA. Foetal and placental samples from the four foetal loss cases were all positive for C. psittaci with 100% agreement between the isothermal swab testing on the farm and qPCR DNA testing at an external laboratory. Genotyping revealed the clonal and identical sequence type 24 (ST24) C. psittaci strains in all samples. C. psittaci was not detected in close contact with mares or their foals. There was no statistically significant difference in foal survival between the close contact mare groups that did and did not receive antimicrobial intervention (P > 0.05). The proposed protocol is intended to raise awareness and begin a discussion for guidelines around handling of chlamydial foetal loss cases in late pregnant mares which pose a zoonotic threat to farm workers and veterinarians.
Rectal MRI Interpretation After Neoadjuvant Therapy

In recent years, several key advances in the management of locally advanced rectal cancer have been made, including the implementation of total mesorectal excision as the standard surgical approach; use of neoadjuvant chemoradiotherapy in selected patients with a high risk of local recurrence, and finally, adoption of organ preservation strategies, through either local excision or nonoperative management in selected patients with clinical complete response following neoadjuvant chemoradiotherapy. This review aims to shed light on the role of rectal MRI in the assessment of treatment response after neoadjuvant therapy, which is especially important given the growing feasibility of nonoperative management. First, an overview of current neoadjuvant therapies and response assessment based on digital rectal examination, endoscopy, and MRI will be provided. Second, the use of a high‐quality restaging rectal MRI protocol will be presented. Third, a step‐by‐step approach to assessing treatment response on restaging rectal MRI following neoadjuvant treatment will be outlined, acknowledging challenges faced by radiologists during MRI interpretation. Finally, research related to response assessment will be discussed.
Association of Measured Quality and Future Financial Performance Among Hospitals Performing Cardiac Surgery

Goal: For decades, hospitals performing cardiac surgery have carried the cost of implementing quality improvement activities and reporting quality outcomes. However, the financial return of such investments is unclear, which weakens the incentive for hospitals to invest in quality improvement activities. This study explored the relationship between a hospital's measured quality and its financial performance. Methods: Using data from the American Hospital Association and Hospital Compare from 2014 to 2018, we performed an observational study of hospitals performing cardiac surgery. We used mixed-effects regression models with fixed-year effects and random intercepts to explore associations between measured quality and hospital financial performance. Our dependent variables were margins (profit divided by revenue) and financial distress; our independent variables included Patient Safety Indicator 90 (PSI-90) and hospital characteristics. Principal Findings: Our sample included 4,927 hospital-years from 1,209 unique hospitals. Hospitals in the worst-performing PSI-90 score quartile experienced a lower operating margin (−1.26%, 95% CI [−2.10 to −0.41], p = .004), a lower total margin (−0.92%, 95% CI [−1.66 to −0.17], p = .016), and an increased odds of financial distress in the next year (OR: 2.12, 95% CI [1.36–3.30], p = .001) when compared with the best-performing hospitals. Practical Applications: Our exploration into financial distress provides managers with a better understanding of the relationship between a hospital's measured quality and its financial position. In reflecting on our findings, hospital leaders may consider viewing patient safety as a modifiable factor that can improve their organization's overall financial health. Our findings suggest that excellent safety performance may be both financially and clinically beneficial to hospitals.
Effects of short‐term unloading and active recovery on human motor unit properties, neuromuscular junction transmission and transcriptomic profile

Electrophysiological alterations of the neuromuscular junction (NMJ) and motor unit potential (MUP) with unloading are poorly studied. We aimed to investigate these aspects and the underlying molecular mechanisms with short‐term unloading and active recovery (AR). Eleven healthy males underwent a 10‐day unilateral lower limb suspension (ULLS) period, followed by 21‐day AR based on resistance exercise. Quadriceps femoris (QF) cross‐sectional area (CSA) and isometric maximum voluntary contraction (MVC) were evaluated. Intramuscular electromyographic recordings were obtained during 10% and 25% MVC isometric contractions from the vastus lateralis (VL). Biomarkers of NMJ molecular instability (serum c‐terminal agrin fragment, CAF), axonal damage (neurofilament light chain) and denervation status were assessed from blood samples and VL biopsies. NMJ and ion channel transcriptomic profiles were investigated by RNA‐sequencing. QF CSA and MVC decreased with ULLS. Increased CAF and altered NMJ transcriptome with unloading suggested the emergence of NMJ molecular instability, which was not associated with impaired NMJ transmission stability. Instead, increased MUP complexity and decreased motor unit firing rates were found after ULLS. Downregulation of ion channel gene expression was found together with increased neurofilament light chain concentration and partial denervation. The AR period restored most of these neuromuscular alterations. In conclusion, the human NMJ is destabilized at the molecular level but shows functional resilience to a 10‐day unloading period at least at relatively low contraction intensities. However, MUP properties are altered by ULLS, possibly due to alterations in ion channel dynamics and initial axonal damage and denervation. These changes are fully reversed by 21 days of AR.
Outcomes of transcatheter aortic valve replacement at teaching versus nonteaching hospitals

Prior studies have demonstrated that outcomes of invasive cardiac interventions may vary by hospital teaching status and volume. As transcatheter aortic valve replacement (TAVR) rapidly expands from teaching to nonteaching hospitals across the country, the clinical impact of hospital teaching status has not been clearly established. This study aimed to compare TAVR outcomes between nonteaching and teaching hospitals.
Perceived Adequacy of Infection Control Practices and Symptoms of Anxiety Among In-Person Elementary School Educators in Ontario

In this paper perceptions of inadequate infection control procedures were associated with elevated levels of anxiety symptoms. Educators, school administrators and policy makers should work collaboratively to design school environments that address perceptions of unmet infection control practices, focusing on physical distancing between educators and students and allowing greater compliance with student masking and cohorting. Objective The aim of this study was to examine the association between the perceived adequacy of infection control practices (ICPs) and symptoms of anxiety among educators in Ontario, Canada. Methods Data from 4947 educators were collected in December 2020. Modified Poisson models assessed the association between adequacy of ICPs and moderate or severe anxiety symptoms, adjusting for a range of covariates. Results Approximately 60% of respondents reported moderate or severe anxiety symptoms. Two-thirds (66.5%) of the sample had less than half of their ICP needs met. Respondents with less than half their ICP needs met were more than three times more likely to have moderate or severe anxiety, compared with respondents with their ICP needs met. Conclusion Findings highlight the importance of adequate administrative and engineering controls in schools, not only to minimize risk of infection, but also for educator's mental health.
Anisotropy and Vp/Vs in the uppermost mantle beneath the western United States from joint analysis of Pn and Sn phases

Pn and Sn phases are valuable for resolving velocity structure in the mantle lid, as they propagate horizontally right below the Moho. Relatively few Sn tomography attempts have been made compared to Pn, because Sn is often highly attenuated or buried in P wave coda. USArray has greatly increased data coverage for regional phases, and both Pn and Sn are routinely picked by network analysts. Here we jointly invert Pn and Sn arrival time residuals with a modified time‐term analysis and a regularized tomography method and present new maps of crustal thickness, uppermost mantle P velocity perturbations, Vp/Vs ratios, and azimuthal anisotropy strength and orientation beneath the western United States. The results indicate partially molten mantle below the Snake River Plain and the Colorado Plateau. The seismic structure of the top ∼40 km of the mantle below the Colorado Plateau differs from that seen at greater depths in other studies, such as surface wave or teleseismic body wave tomography, whereas the Snake River Plain anomaly just below the Moho is comparable to structures seen at about ∼200 km depth. Pn fast axes provide complementary information to SKS shear wave splitting observations, and our analysis indicates that in several regions in the western United States the orientation of azimuthal anisotropy changes with depth in the upper mantle. However, we have so far been unable to resolve shear wave splitting directly in Sn waveforms, which seem to be dominated by Sn‐SV energy.