Miracle-dz/UniFAR-FTUs huggingface dataset:
Infection and Transmission of SARS-CoV-2 B.1.617.2 Lineage (Delta Variant) among Fully Vaccinated Individuals

The SARS-CoV-2 lineage B.1. 617.2 (Delta variant) emerged in Asia and rapidly spread to other countries, becoming the dominant circulating lineage. Worldwide infections with B.1. 617.2 peaked at a time in which vaccination rates were increasing. ABSTRACT The emergence of the SARS-CoV-2 B.1. 617.2 lineage (Delta variant) in 2021 was associated with increased case numbers and test positivity rates, including a large number of infections in fully vaccinated individuals. Here, we describe the findings of an investigation conducted in Tompkins County, New York, to evaluate factors underlying a significant uptick in the number of coronavirus disease 2019 (COVID-19) cases observed in the months of July and August 2021. We performed genomic surveillance and genotyping as well as virological assessments to determine infectivity of the virus in a select number of clinical diagnostic samples. Genomic sequence analyses revealed complete replacement of the B.1. 1.7 lineage (Alpha variant) with the B.1. 617.2 lineage (Delta variant) between July 1 and August 4 2021. We observed a strong association between viral RNA loads detected by real-time reverse transcriptase PCR and infectious virus detected in respiratory secretions by virus titration. A marked increase in positive cases among fully vaccinated individuals was observed. The sequence divergence between two index Delta variant cases in April and May, and the cases after July 1st, revealed independent Delta variant introductions in Tompkins County. Contact tracing information enabled the detection of clusters of connected cases within closely related phylogenetic clusters. We also found evidence of transmission between vaccinated individuals and between vaccinated and unvaccinated individuals. This was confirmed by detection and isolation of infectious virus from a group of individuals within epidemiologically connected transmission clusters, confirming shedding of high viral loads and transmission of the virus by fully vaccinated individuals. IMPORTANCE The SARS-CoV-2 lineage B.1. 617.2 (Delta variant) emerged in Asia and rapidly spread to other countries, becoming the dominant circulating lineage. Worldwide infections with B.1. 617.2 peaked at a time in which vaccination rates were increasing. In this study, we present data characterizing the emergence of SARS-CoV-2 lineage B.1. 617.2 (Delta variant) in Tompkins County, New York, which has one of the highest vaccination rates in the state. We present evidence demonstrating infection, replication, and transmission of SARS-CoV-2 lineage B.1. 617.2 (Delta variant) between fully vaccinated individuals. Importantly, infectious virus loads were determined in a subset of samples and demonstrated shedding of high viral titers in respiratory secretions of vaccinated individuals.
Updates of cancer hallmarks in patients with inborn errors of immunity

Purpose of review The development of cancer in patients with genetically determined inborn errors of immunity (IEI) is much higher than in the general population. The hallmarks of cancer are a conceptualization tool that can refine the complexities of cancer development and pathophysiology. Each genetic defect may impose a different pathological tumor predisposition, which needs to be identified and linked with known hallmarks of cancer. Recent findings Four new hallmarks of cancer have been suggested, recently, including unlocking phenotypic plasticity, senescent cells, nonmutational epigenetic reprogramming, and polymorphic microbiomes. Moreover, more than 50 new IEI genes have been discovered during the last 2 years from which 15 monogenic defects perturb tumor immune surveillance in patients. Summary This review provides a more comprehensive and updated overview of all 14 cancer hallmarks in IEI patients and covers aspects of cancer predisposition in novel genes in the ever-increasing field of IEI.
Clinical outcomes of therapy-related acute myeloid leukemia: over 20 years long single center retrospective analysis.

INTRODUCTION Therapy-related acute myeloid leukemia (t-AML), a life-threatening complication of cytotoxic therapy, represents an emerging challenge of modern oncology. OBJECTIVES Evaluation of t-AML clinical outcomes, considering genetic changes and treatment intensity. PATIENTS AND METHODS We conducted a retrospective analysis of all consecutive AML patients from one hematology center (hospitalisation between 2000-2021). t-AML diagnosis was established according to the 2016 WHO criteria. Overall survival (OS) and progression free survival (PFS) were defined to evaluate treatment outcomes. Retrospective identification of 17p13 deletion and TP53 mutation was conducted. RESULTS Among 743 AML patients, 60 (8.1%) were diagnosed with t-AML (63.4% with previous solid tumors). Complex karyotype (CK) and 17p13 deletion were detected in 26.8% and 26.7% of t-AML, respectively, while FLT3-ITD and TP53 mutations occurred in 15.4% and 12.5% t-AML. Median OS and PFS were 13 and 8 months, respectively. Survival outcomes were superior for alloHCT treatment than intensive chemotherapy alone (median OS: 47 vs 7 months, P=0.01). APL patients did not reach median OS and worse survival was noted within CK than non-CK t-AML (median OS: 6 vs 24 months, P=0.02). In intensively treated t-AML, survival was better for patients under 64 years of age (P=0.03). In the multivariable Cox proportional hazards regression model, alloHCT was associated with superior OS (HR=0.19, 95% CI=0.04-0.91, P=0.04). Moreover, we noted high frequency of treatment-related complications of t-AML. CONCLUSIONS Our study revealed that prognosis of t-AML varies. Hence, the treatment strategy should rely on performing alloHCT as soon as possible in patients with adverse genetics.
Sustained Drought, but Not Short-Term Warming, Alters the Gut Microbiomes of Wild Anolis Lizards

As climate change progresses, it is crucial to understand how animals will respond to shifts in their local environments. One component of this response involves changes in the microbial communities living in and on host organisms. ABSTRACT As rising temperatures threaten biodiversity across the globe, tropical ectotherms are thought to be particularly vulnerable due to their narrow thermal tolerance ranges. Nevertheless, physiology-based models highlighting the vulnerability of tropical organisms rarely consider the contributions of their gut microbiota, even though microbiomes influence numerous host traits, including thermal tolerance. We combined field and lab experiments to understand the response of the slender anole lizard (Anolis apletophallus) gut microbiome to climatic shifts of various magnitude and duration. First, to examine the effects of long-term climate warming in the wild, we transplanted lizards from the mainland Panama to a series of warmer islands in the Panama Canal and compared their gut microbiome compositions after three generations of divergence. Next, we mimicked the effects of a short-term “heat-wave” by using a greenhouse experiment and explored the link between gut microbiome composition and lizard thermal physiology. Finally, we examined variation in gut microbiomes in our mainland population in the years both before and after a naturally occurring drought. Our results suggest that slender anole microbiomes are surprisingly resilient to short-term warming. However, both the taxonomic and predicted functional compositions of the gut microbiome varied by sampling year across all sites, suggesting that the drought may have had a regional effect. We provide evidence that short-term heat waves may not substantially affect the gut microbiota, while more sustained climate anomalies may have effects at broad geographic scales. IMPORTANCE As climate change progresses, it is crucial to understand how animals will respond to shifts in their local environments. One component of this response involves changes in the microbial communities living in and on host organisms. These “microbiomes” can affect many processes that contribute to host health and survival, yet few studies have measured changes in the microbiomes of wild organisms experiencing novel climatic conditions. We examined the effects of shifting climates on the gut microbiome of the slender anole lizard (Anolis apletophallus) by using a combination of field and laboratory studies, including transplants to warm islands in the Panama Canal. We found that slender anole microbiomes remain stable in response to short-term warming but may be sensitive to sustained climate anomalies, such as droughts. We discuss the significance of these findings for a species that is considered highly vulnerable to climate change.
Preexercise High-Fat Meal Following Carbohydrate Loading Attenuates Glycogen Utilization During Endurance Exercise in Male Recreational Runners

Abstract Iwayama, K, Tanabe, Y, Yajima, K, Tanji, F, Onishi, T, and Takahashi, H. Preexercise high-fat meal following carbohydrate loading attenuates glycogen utilization during endurance exercise in male recreational runners. J Strength Cond Res 37(3): 661–668, 2023—This study aimed to investigate whether one preexercise high-fat meal can increase glycogen conservation during endurance exercise, as compared with one preexercise high-carbohydrate meal. Ten young male recreational runners (22.0 ± 0.6 years; 171.3 ± 0.9 cm; 58.3 ± 1.9 kg; maximal oxygen uptake [V̇o2max], 62.0 ± 1.6 ml·kg−1·min−1) completed 2 exercise trials after high-carbohydrate loading: eating a high-carbohydrate (CHO; 7% protein, 13% fat, 80% carbohydrate) meal or eating a high-fat (FAT; 7% protein, 42% fat, 52% carbohydrate) meal 3.5 hours before exercise. The order of the 2 trials was randomized, and the interval between trials was at least 1 week. The experimental exercise consisted of running on a treadmill for 60 minutes at 95% of each subject's lactate threshold. Muscle and liver glycogen content were assessed using noninvasive carbon magnetic resonance spectroscopy before the experimental meal as well as before and after exercise; respiratory gases were measured continuously during exercise. The respiratory exchange ratio during exercise was statistically lower in the FAT trial than in the CHO trial (p < 0.01). In addition, muscle (p < 0.05) and liver (p < 0.05) glycogen utilization during exercise was less in the FAT trial than in the CHO trial. Therefore, one high-fat meal following carbohydrate loading reduced muscle and liver glycogen use during the 60-minute exercise. These results suggest that this dietary approach may be applied as a strategy to optimize energy utilization during endurance exercise.
Confirmation of fifth Candida auris clade by whole genome sequencing

ABSTRACT Candida auris has emerged globally as a multidrug-resistant pathogen causing outbreaks in health care facilities. Whole genome sequencing (WGS) analysis has identified four major clades, while earlier WGS data from a single Iranian isolate suggested the existence of a potential fifth clade. Here, we confirm the existence of this fifth clade by providing WGS data of another four Iranian isolates. These clade V isolates differed less than 100 single-nucleotide polymorphisms (SNPs) between each other, while they were separated from the other clades by more than 200,000 SNPs. Two of these isolates were resistant to fluconazole and were found to harbour mutations in the TAC1b and ERG11 genes.
Predicting Hospitalization among Medicaid Home- and Community-Based Services Users Using Machine Learning Methods

We compare multiple machine learning algorithms and develop models to predict future hospitalization among Home- and Community-Based Services (HCBS) Users. Furthermore, we calculate feature importance, the score of input variables based on their importance to predict the outcome, to identify the most relevant variables to predict hospitalization. We use the 2012 national Medicaid Analytic eXtract data and Medicare Provider Analysis and Review data. Predicting any hospitalization, Random Forest appears to be the most robust approach, though XGBoost achieved similar predictive performance. While the importance of features varies by algorithm, chronic conditions, previous hospitalizations, as well as use of services for ambulance, personal care, and durable medical equipment were generally found to be important predictors of hospitalization. Utilizing prediction models to identify those who are prone to hospitalization could be useful in developing early interventions to improve outcomes among HCBS users.
M6A RNA Methylation-Based Epitranscriptomic Modifications in Plasticity-Related Genes via miR-124-C/EBPα-FTO-Transcriptional Axis in the Hippocampus of Learned Helplessness Rats

Abstract Background Impaired synaptic plasticity has been linked to dynamic gene regulatory network changes. Recently, gene regulation has been introduced with the emerging concept of unique N6-methyladenosine (m6A)-based reversible transcript methylation. In this study, we tested whether m6A RNA methylation may potentially serve as a link between the stressful insults and altered expression of plasticity-related genes. Methods Expression of plasticity genes Nr3c1, Creb1, Ntrk2; m6A-modifying enzymes Fto, methyltransferase like (Mettl)-3 and 14; DNA methylation enzymes Dnmt1, Dnmt3a; transcription factor C/ebp-α; and miRNA-124-3p were determined by quantitative polymerase chain reaction (qPCR) in the hippocampus of rats that showed susceptibility to develop stress-induced depression (learned helplessness). M6A methylation of plasticity-related genes was determined following m6A mRNA immunoprecipitation. Chromatin immunoprecipitation was used to examine the endogenous binding of C/EBP-α to the Fto promoter. MiR-124–mediated post-transcriptional inhibition of Fto via C/EBPα was determined using an in vitro model. Results Hippocampus of learned helplessness rats showed downregulation of Nr3c1, Creb1, and Ntrk2 along with enrichment in their m6A methylation. A downregulation in demethylating enzyme Fto and upregulation in methylating enzyme Mettl3 were also noted. The Fto promoter was hypomethylated due to the lower expression of Dnmt1 and Dnmt3a. At the same time, there was a lower occupancy of transcription factor C/EBPα on the Fto promoter. Conversely, C/ebp-α transcript was downregulated via induced miR-124-3p expression. Conclusions Our study mechanistically linked defective C/EBP-α-FTO-axis, epigenetically influenced by induced expression of miR-124-3p, in modifying m6A enrichment in plasticity-related genes. This could potentially be linked with abnormal neuronal plasticity in depression.
Genotyping of patients treated with selective serotonin reuptake inhibitors.

BACKGROUND Selective serotonin reuptake inhibitors (SSRIs) are used by over 180,000 people in Norway. The enzymes CYP2D6 and CYP2C19 are key in the metabolism of SSRI antidepressants. The serotonin transporter coded by SLC6A4 may be significant for the efficacy of the drugs. MATERIAL AND METHOD All patients who had undergone genotyping for CYP2D6, CYP2C19 and SLC6A4 at the Centre for Psychopharmacology in 2020 were included, irrespective of indication. For those patients where data were available, CYP2C19 genotype was linked to serum concentration measurement of escitalopram, which is the most commonly used SSRI drug. RESULTS Out of 3,492 patients, 432 (12.4 %) had a combination of genotypes of CYP2D6, CYP2C19 and SLC6A4 considered to lead to the most favourable metabolism and efficacy of SSRI antidepressants. The dose requirement in patients with poor CYP2C19 metabolism was more than halved to achieve the same concentration of escitalopram compared to patients with normal metabolism. INTERPRETATION Our findings demonstrate the low prevalence of the most favourable genotype combination for response to SSRIs. Genotype combinations probably contribute to the wide variation between individuals in the efficacy of these drugs and the fact that treatment does not produce the desired outcome in many patients.
Measures of tonic and phasic activity of the locus coeruleus—norepinephrine system in children with autism spectrum disorder: An event‐related potential and pupillometry study

A growing body of research suggests that locus coeruleus‐norepinephrine (LC‐NE) system may function differently in individuals with autism spectrum disorder (ASD). Understanding the dynamics of both tonic (resting pupil diameter) and phasic (pupil dilation response [PDR] and event‐related potential [ERP]) indices may provide meaningful insights about the nature of LC‐NE function in ASD. Twenty‐four children with ASD and 27 age‐ and nonverbal‐IQ matched typically developing (TD) children completed two experiments: (1) a resting eye‐tracking task to measure tonic pupil diameter, and (2) a three‐stimulus oddball paradigm to measure phasic responsivity using PDR and ERP. Consistent with prior reports, our results indicate that children with ASD exhibit increased tonic (resting pupil diameter) and reduced phasic (PDR and ERP) activity of the LC‐NE system compared to their TD peers. For both groups, decreased phasic responsivity was associated with increased resting pupil diameter. Lastly, tonic and phasic LC‐NE indices were primarily related to measures of attention‐deficit/hyperactivity disorder (ADHD), and not ASD, symptomatology. These findings expand our understanding of neurophysiological differences present in ASD and demonstrate that aberrant LC‐NE activation may be associated with atypical arousal and decreased responsivity to behaviorally‐relevant information in ASD.
The Role of Communication Style and External Motivators in Predicting Vaccination Experiences and Intentions: An Experimental Vignette Study

ABSTRACT This vignette-based study examined in a sample of unvaccinated Belgian citizens (N = 1918; M age = 45.99) how health care workers could foster reflection about and intentions to get vaccinated against COVID-19 by experimentally varying their communication style (i.e., autonomy-supportive vs. controlling) and the reference to external motivators (i.e., use of a monetary voucher or corona pass vs. the lack thereof). Each participant was randomly assigned to one of six conditions and rated a vignette in terms of anticipated autonomy satisfaction, perceived effectiveness, reflection, and vaccination intention. An autonomy-supportive, relative to a controlling, communication style predicted greater autonomy need satisfaction, which in turn related positively to perceived effectiveness, reflection, and vaccination intention. External motivators failed to generate positive effects compared to the control condition. The findings highlight the critical role of autonomy support in promoting a self-endorsed decision to get vaccinated.
Contract Cheating and Ghostwriting among University Students in Health Specialties

Contract cheating and ghostwriting are forms of misconduct that are unethical and a serious academic issue, especially among healthcare professionals, as they directly impact patient health. To date, research on this area in the Middle East has been limited. Therefore, we used a validated self-administered questionnaire to investigate the awareness, perceptions, and reasons for these behaviors among 682 students in health specialties at five universities in Riyadh, Saudi Arabia. The majority of the students (60.1%) were unaware of the terms “contract cheating” and “ghostwriting,” and 69.5% had not received any prior training on integrity. However, having prior training had a positive effect on awareness levels, and respondents attending private universities were significantly more aware than those attending public universities. The factors that contributed to contract cheating behavior included poor time management, English language difficulties, and a lack of writing skills. These findings emphasize the need for integrity training at the national level to raise awareness.
Systematic review of exercise therapy in the management of post-thrombotic syndrome

Objectives Exercise improves haemodynamic parameters in patients with chronic venous disease. There is a paucity of evidence on its effect in post-thrombotic syndrome (PTS). The aim of this systematic review is to assess the impact of exercise in PTS. Methods Adhering to PRISMA guidelines and following PROSPERO registration (CRD42021220924), MEDLINE, Cochrane Library, EMBASE database, and trial registries were searched on 19th May 2022. Results One article met the inclusion criteria and a narrative synthesis was carried out. The included randomised controlled trial reported a between-group mean difference of 4.6 points (p = .027) in the VEINES-QOL score and −2.0 points (p = .14) in the Villalta score, in favour of exercise therapy. The statistical significance threshold was not reached. Conclusion Data on exercise in PTS remains sparse but exercise appears to be a safe intervention. In the context of this literature, a potential future trial and outcome reporting measures are suggested.
Supporting Expressive and Faithful Pictorial Visualization Design with Visual Style Transfer

Pictorial visualizations portray data with figurative messages and approximate the audience to the visualization. Previous research on pictorial visualizations has developed authoring tools or generation systems, but their methods are restricted to specific visualization types and templates. Instead, we propose to augment pictorial visualization authoring with visual style transfer, enabling a more extensible approach to visualization design. To explore this, our work presents Vistylist, a design support tool that disentangles the visual style of a source pictorial visualization from its content and transfers the visual style to one or more intended pictorial visualizations. We evaluated Vistylist through a survey of example pictorial visualizations, a controlled user study, and a series of expert interviews. The results of our evaluation indicated that Vistylist is useful for creating expressive and faithful pictorial visualizations.
The unusual convergence of steroid catabolic pathways in Mycobacterium abscessus

Significance Cholesterol catabolism, a potential therapeutic target in Mycobacterium tuberculosis, remains underexplored in nontuberculosis mycobacteria. Our study revealed that the opportunistic pathogen Mycobacterium abscessus contains catabolic pathways for cholesterol and 4-androstenedione, and that among strains of the M. abscessus complex, the two pathways converge at a point that is unique among steroid-degrading bacteria. Consistent with it being the enzyme at the point of convergence, HsaD efficiently transformed substrates from both pathways. A ΔhsaD mutant of M. abscessus did not grow in macrophages, indicating that cholesterol is a growth substrate for intracellular bacteria. The mutant also showed steroid-dependent toxicity. This study provides insight into the bacterial catabolism of steroids and the nutritional requirements of intracellular M. abscessus.
Structures of a large prolate virus capsid in unexpanded and expanded states generate insights into the icosahedral virus assembly

Significance Virus assembly occurs by repeated association of tiny building blocks, the capsid protein subunits. The assembled structures are highly dynamic and undergo maturation transformations, ultimately generating an infectious virion particle. We describe, at near-atomic resolution, a major “expansion” transformation in a large, prolate, icosahedral virus, the bacteriophage T4. It involves large-scale movements and remodeling of capsid protein domains that lead to extraordinary capsid stability and additional 70% increase in volume. Small changes in capsid subunit interactions lead to profound alterations in capsid size and volume, allowing evolution of viral variants with survival advantages. These basic principles are relevant to all viruses, particularly the herpesviruses that share common structural features and assembly mechanisms with T4.