Miracle-dz/UniFAR-FTUs huggingface dataset:
Predicted impact of the viral mutational landscape on the cytotoxic response against SARS-CoV-2

The massive assessment of immune evasion due to viral mutations that increase COVID-19 susceptibility can be computationally facilitated. The adaptive cytotoxic T response is critical during primary infection and the generation of long-term protection. Here, potential HLA class I epitopes in the SARS-CoV-2 proteome were predicted for 2,915 human alleles of 71 families using the netMHCIpan EL algorithm. Allele families showed extreme epitopic differences, underscoring genetic variability of protective capacity between humans. Up to 1,222 epitopes were associated with any of the twelve supertypes, that is, allele clusters covering 90% population. Next, from all mutations identified in ~118,000 viral NCBI isolates, those causing significant epitope score reduction were considered epitope escape mutations. These mutations mainly involved non-conservative substitutions at the second and C-terminal position of the ligand core, or total ligand removal by large recurrent deletions. Escape mutations affected 47% of supertype epitopes, which in 21% of cases concerned isolates from two or more sub-continental areas. Some of these changes were coupled, but never surpassed 15% of evaded epitopes for the same supertype in the same isolate, except for B27. In contrast to most supertypes, eight allele families mostly contained alleles with few SARS-CoV-2 ligands. Isolates harboring cytotoxic escape mutations for these families co-existed geographically within sub-Saharan and Asian populations enriched in these alleles according to the Allele Frequency Net Database. Collectively, our findings indicate that escape mutation events have already occurred for half of HLA class I supertype epitopes. However, it is presently unlikely that, overall, it poses a threat to the global population. In contrast, single and double mutations for susceptible alleles may be associated with viral selective pressure and alarming local outbreaks. The integration of genomic, geographical and immunoinformatic information eases the surveillance of variants potentially affecting the global population, as well as minority subpopulations.
Towards a Neurometric-based Construct Validity of Trust

Trust is a nebulous construct central to successful cooperative exchanges and interpersonal relationships. In this study, we introduce a new approach to establishing construct validity of trust using “neurometrics”. We develop a whole-brain multivariate pattern capable of classifying whether new participants will trust a relationship partner in the context of a cooperative interpersonal investment game (n=40) with 90% accuracy and find that it also generalizes to a variant of the same task collected in a different country with 82% accuracy (n=17). Moreover, we establish the convergent and discriminant validity by testing the pattern on thirteen separate datasets (n=1,427) and find that trust is reliably related to beliefs of safety, inversely related to negative affect, but unrelated to reward, cognitive control, social perception, theory of mind, and self-referential processing. Together these results provide support for the notion that the psychological experience of trust contains elements of beliefs of reciprocation and fear of betrayal aversion. Contrary to our predictions, we found no evidence that trust is related to anticipated reward. This work demonstrates how “neurometrics” can be used to characterize the psychological processes associated with brain-based multivariate representations.
Novel microbial syntrophies identified by longitudinal metagenomics

Identifying species interactions in a microbial community and how this relates to community function is a key challenge. Towards addressing this challenge, we present here an extensive genome-resolved, longitudinal dataset and associated metadata. We collected weekly samples of microbial communities and recorded operating conditions from industrial methane producing anaerobic digestion reactors for a year. This allowed us to recover 2240 dereplicated metagenome assembled genomes (dMAGs), together with their coverage dynamics and functional annotations from which functional traits were inferred. Of these dMAGs, 1910 were novel species, with 22 representing novel orders and classes. Methanogenic communities are expected to be strongly structured by syntrophic and other associations between the methanogens and syntrophs that produce their substrates. We identified 450 potential syntrophic dMAGs by searching for pairs of methanogenic and non-methanogenic dMAGs that had highly correlated time-series. Genomes of potential syntrophs were enriched for oxidoreductases and sugar transport genes and there was a strong taxonomic signal in their associations with methanogens. Of particular note, we found that Bathyarchaeiea associated specifically with methanogens from the Thermoplasmata, and Thermococci classes. Same syntrophic associations were only rarely observed across multiple reactors, suggesting that syntrophies might be facultative, with particular strains within a species forming syntrophic associations only sometimes and not necessarily always with the same methanogenic partner. The presented results show that longitudinal metagenomics is a highly valuable approach for identifying species and their interactions in microbial communities. One Sentence Summary Longitudinal study of microbial communities identifies novel species and predicts their interactions and role in community function.
Linguistic modulation of the neural encoding of phonemes

Speech comprehension entails the neural mapping of the acoustic speech signal onto learned linguistic units. This acousto-linguistic transformation is bi-directional, whereby higher-level linguistic processes (e.g., semantics) modulate the acoustic analysis of individual linguistic units. Here, we investigated the cortical topography and linguistic modulation of the most fundamental linguistic unit, the phoneme. We presented natural speech and ‘phoneme quilts’ (pseudo-randomly shuffled phonemes) in either a familiar (English) or unfamiliar (Korean) language to native English speakers while recording fMRI. This allowed us to dissociate the contribution of acoustic vs. linguistic processes towards phoneme analysis. We show that (1) the acoustic analysis of phonemes is modulated by linguistic analysis and (2) that for this modulation both of acoustic and phonetic information need to be incorporated. These results suggest that the linguistic modulation of cortical sensitivity to phoneme classes minimizes prediction error during natural speech perception, thereby aiding speech comprehension in challenging listening situations.
Gut microbial diversity in stingless bees is linked to host wing size and is influenced by geography

Stingless bees are globally important social corbiculate bees, fulfilling critical pollination roles in many ecosystems; however, their gut microbiota, especially fungal communities, are not well characterized to date. We collected 121 bee samples from two species, Tetragonula carbonaria and Austroplebeia australis, across a distance of 1,200 km of eastern Australia, and analysed their gut microbiomes. We found that the gut bacterial richness of T. carbonaria was influenced by geography (latitude and longitude) and positively correlated to an established fitness indicator in insects; namely, host forewing length/size that relates to flight capacity of stingless bees. We characterized the core microbiomes of the two bees and found that they consisted of the bacterial taxa Snodgrassella, Lactobacillus, Acetobacteraceae and Bombella, and the fungal taxa Didymellaceae, Monocilium mucidum, Malassezia restricta and Aureobasidium pullulans. Both host species identity and management (wild or managed) significantly influenced the gut microbial diversity and composition, and similarity between colonies declined as the geographical distance between them increased. This result was also supported by our co-existing network analyses. Overall, we have thoroughly analysed stingless bee gut microbiomes, and provided novel evidence that T. carbonaria bees with larger wings or from more southern populations have higher microbial diversity in their guts. Originality-Significance Statement Beneficial interactions between insects and their microbial symbionts are pivotal for their fitness. In this study, we analysed the gut microbiomes of two stingless bee species, Tetragonula carbonaria and Austroplebeia australis, that are widespread and important pollinators in Australia. We characterized their gut microbiomes and detected a significant positive correlation between gut bacterial richness and host forewing size for T. carbonaria; the first time that gut microbial diversity has been linked to a morphological trait in stingless bees. Furthermore, we found that host species’ identity, management type (wild or managed) and geography all significantly influenced bee gut microbial diversity and composition, and were able to describe both bacterial and fungal core microbial taxa. This study reveals novel understandings of stingless bee gut microbiomes and provides the basis for utilizing microbial strategies to maintain colony health.
Members of the CUGBP Elav-Like Family of RNA-Binding Proteins are Expressed in Distinct Populations of Primary Sensory Neurons

Primary sensory Dorsal Root Ganglia (DRG) neurons are diverse, with distinct populations that respond to specific stimuli. Previously, we observed that functionally distinct populations of DRG neurons express mRNA transcript variants with different 3’ untranslated regions (3’UTR’s). 3’UTRs harbor binding sites for interaction with RNA-binding proteins (RBPs) for transporting mRNAs to subcellular domains, modulating transcript stability and regulating the rate of translation. In the current study, analysis of publicly available single-cell RNA-Sequencing (scRNA-Seq) data generated from adult mice revealed that 17 3’UTR-binding RBPs were enriched in specific populations of DRG neurons. This included 4 members of the CUGBP Elav-Like Family (CELF): CELF2 and CELF4 were enriched in peptidergic, CELF6 in both peptidergic and nonpeptidergic and CELF3 in tyrosine hydroxylase-expressing neurons. Immunofluorescence studies confirmed that 60% of CELF4+ neurons are small diameter C fibers and 33% medium diameter myelinated (likely Aδ) fibers and showed that CELF4 is distributed to peripheral termini. Co-expression analyses using transcriptomic data and immunofluorescence revealed that CELF4 is enriched in nociceptive neurons that express GFRA3, CGRP and the capsaicin receptor TRPV1. Re-analysis of published transcriptomic data from macaque DRG revealed a highly similar distribution of CELF members, and re-analysis of single-nucleus RNA sequencing data derived mouse and rat DRG after sciatic injury revealed differential expression of CELFs in specific populations of sensory neurons. We propose that CELF RNA-binding proteins may regulate the fate of mRNAs in populations of nociceptors, and may play a role in pain and/or neuronal regeneration following nerve injury.
Tactile suppression stems from sensation-specific sensorimotor predictions

The ability to sample sensory information with our hands is crucial for smooth and efficient interactions with the world. Despite this important role of touch, tactile sensations on a moving hand are perceived weaker than when presented on the same but stationary hand.1–3 This phenomenon of tactile suppression has been explained by predictive mechanisms, such as forward models, that estimate future sensory states of the body on the basis of the motor command and suppress the associated predicted sensory feedback.4 The origins of tactile suppression have sparked a lot of debate, with contemporary accounts claiming that suppression is independent of predictive mechanisms and is instead akin to unspecific gating.5 Here, we target this debate and provide evidence for sensation-specific tactile suppression due to sensorimotor predictions. Participants stroked with their finger over textured surfaces that caused predictable vibrotactile feedback signals on that finger. Shortly before touching the texture, we applied external vibrotactile probes on the moving finger that either matched or mismatched the frequency generated by the stroking movement. We found stronger suppression of the probes that matched the predicted sensory feedback. These results show that tactile suppression is not limited to unspecific gating but is specifically tuned to the predicted sensory states of a movement.
Fly Cell Atlas: a single-cell transcriptomic atlas of the adult fruit fly

The ability to obtain single cell transcriptomes for stable cell types and dynamic cell states is ushering in a new era for biology. We created the Tabula Drosophilae, a single cell atlas of the adult fruit fly which includes 580k cells from 15 individually dissected sexed tissues as well as the entire head and body. Over 100 researchers from the fly community contributed annotations to >250 distinct cell types across all tissues. We provide an in-depth analysis of cell type-related gene signatures and transcription factor markers, as well as sexual dimorphism, across the whole animal. Analysis of common cell types that are shared between tissues, such as blood and muscle cells, allowed the discovery of rare cell types and tissue-specific subtypes. This atlas provides a valuable resource for the entire Drosophila community and serves as a comprehensive reference to study genetic perturbations and disease models at single cell resolution.
Multifaceted roles of SAMHD1 in cancer

SAMHD1 is discussed as a tumour suppressor protein, but its potential role in cancer has only been investigated in very few cancer types. Here, we performed a systematic analysis of the TCGA (adult cancer) and TARGET (paediatric cancer) databases, the results of which did not suggest that SAMHD1 should be regarded as a bona fide tumour suppressor. SAMHD1 mutations that interfere with SAMHD1 function were not associated with poor outcome, which would be expected for a tumour suppressor. High SAMHD1 tumour levels were associated with increased survival in some cancer entities and reduced survival in others. Moreover, the data suggested differences in the role of SAMHD1 between males and females and between different races. Often, there was no significant relationship between SAMHD1 levels and cancer outcome. Taken together, our results indicate that SAMHD1 may exert pro-or anti-tumourigenic effects and that SAMHD1 is involved in the oncogenic process in a minority of cancer cases. These findings seem to be in disaccord with a perception and narrative forming in the field suggesting that SAMHD1 is a tumour suppressor. A systematic literature review confirmed that most of the available scientific articles focus on a potential role of SAMHD1 as a tumour suppressor. The reasons for this remain unclear but may include confirmation bias and publication bias. Our findings emphasise that hypotheses, perceptions, and assumptions need to be continuously challenged by using all available data and evidence.
Factors Associated With Burnout, Post-traumatic Stress and Anxio-Depressive Symptoms in Healthcare Workers 3 Months Into the COVID-19 Pandemic: An Observational Study

Objective: This study examined how best to identify modifiable protective and risk factors for burnout in healthcare workers in the face of the COVID-19 pandemic. Individual, occupational, organizational and social factors were investigated. The study also assessed the impact of these factors on post-traumatic stress disorder (PTSD), anxiety, and depression. Methods: Healthcare workers in the Quebec (Canada) healthcare system were recruited between May 21 to June 5, 2020. Participants answered an electronic survey 3 months after the COVID-19 epidemic outbreak began in Canada. Using the Maslach Burnout Inventory, PTSD Checklist for DSM-5, and Hospital Anxiety and Depression Scale, we studied the prevalence of burnout, PTSD, anxiety and depression in this cohort. Multivariable logistic or linear regression models including resilience, social and organizational support, workload and access to mental health help, simulation techniques and protective personal equipment (PPE) as well as perception of PPE security were conducted for each outcome. Results: In mid-June 2020, 467 participants completed the survey. We found that half (51.8%) of the respondents experienced burnout characterized by emotional exhaustion and/or depersonalization at least once a week. In total, 158 healthcare workers (35.6%) displayed severe symptoms of at least one of the mental health disorders (24.3% PTSD, 23.3% anxiety, 10.6% depression). Resilience (OR = 0.69, 95% CI: [0.55–0.87]; p = 0.002) and perceived organizational support (OR = 0.75, 95% CI: [0.61–0.93]; p = 0.009) were significantly associated with burnout and other outcomes. Social support satisfaction, perception of PPE security, work type and environment, mental health antecedents and reassignment were associated with PTSD and/or anxiety and/or depression, but not burnout. Conclusion: Future studies should address primarily resilience and perceived organizational support to promote mental health and prevent burnout, PTSD, anxiety and depression.
Circulating miRNAs as Auxiliary Diagnostic Biomarkers for Multiple Myeloma: A Systematic Review, Meta-Analysis, and Recommendations

Multiple myeloma (MM) is a hematologic malignancy characterized by aberrant expansion of monoclonal plasma cells with high mortality and severe complications due to the lack of early diagnosis and timely treatment. Circulating miRNAs have shown potential in the diagnosis of MM with inconsistent results, which remains to be fully assessed. Here we updated a meta-analysis with relative studies and essays published in English before Jan 31, 2021. After steps of screening, 32 studies from 11 articles that included a total of 627 MM patients and 314 healthy controls were collected. All data were analyzed by REVMAN 5.3 and Stata MP 16, and the quality of included literatures was estimated by Diagnostic Accuracy Study 2 (QUADAS-2). The pooled area under the curve (AUC) shown in summary receiver operating characteristic (SROC) analyses of circulating miRNAs was 0.87 (95%CI, 0.81–0.89), and the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were 0.79, 0.86, 5, 0.27, 22, respectively. Meta-regression and subgroup analysis exhibited that “miRNA cluster”, patient “detailed stage or Ig isotype” accounted for a considerable proportion of heterogeneity, revealing the importance of study design and patient inclusion in diagnostic trials; thus standardized recommendations were proposed for further studies. In addition, the performance of the circulating miRNAs included in MM prognosis and treatment response prediction was summarized, indicating that they could serve as valuable biomarkers, which would expand their clinical application greatly. Systematic Review Registration https://www.crd. york.ac. uk/prospero/display_record. php? RecordID=234297, PROSPERO, identifier (CRD42021234297).
Anxiety, Loneliness, Drug Craving, and Depression Among Substance Abusers in Sichuan Province, China

Studies have reported that anxiety had a positive effect on depression among substance abusers in males. However, little is known about the mechanism underlying this relationship in substance abusers in males. The purpose of this study was to investigate the mediating effect of loneliness and drug craving between anxiety and depression in substance abusers in males. State-Trait Anxiety Inventory, The UCLA Loneliness Scale, Drug Craving Scale, and The Center for Epidemiologic Studies Depression Scale were employed into this study to investigate 585 substance abusers in males (age range of 20–58 years: M = 33.21, SD = 6.97). Structural equation modeling and the bootstrap approach were used to analyze the mediating effect of loneliness and drug craving on the relationship between anxiety and depression. The results indicated that: Loneliness had a significant positive correlation with anxiety (r = 0.37, p < 0.001) and depression (r = 0.49, p < 0.001); Drug craving had a significant positive correlation with anxiety (r = 0.28, p < 0.001) and depression (r = 0.39, p < 0.001). Loneliness and drug craving mediated the link between anxiety and depression. There was a significant positive correlation between substance abusers in male’s anxiety, loneliness, drug craving, and depression. Loneliness and drug craving had a significant mediating effect on the relationship between anxiety and depression. Therefore, it was suggested that substance abusers in male’s anxiety and depression might be improved and driven by decreasing loneliness and drug craving. Targeted interventions to decrease substance abusers in male’s loneliness and drug craving should be developed, implemented, and help them to recover.
Precision Medicine Gains Momentum: Novel 3D Models and Stem Cell-Based Approaches in Head and Neck Cancer

Despite the current progress in the development of new concepts of precision medicine for head and neck squamous cell carcinoma (HNSCC), in particular targeted therapies and immune checkpoint inhibition (CPI), overall survival rates have not improved during the last decades. This is, on the one hand, caused by the fact that a significant number of patients presents with late stage disease at the time of diagnosis, on the other hand HNSCC frequently develop therapeutic resistance. Distinct intratumoral and intertumoral heterogeneity is one of the strongest features in HNSCC and has hindered both the identification of specific biomarkers and the establishment of targeted therapies for this disease so far. To date, there is a paucity of reliable preclinical models, particularly those that can predict responses to immune CPI, as these models require an intact tumor microenvironment (TME). The “ideal” preclinical cancer model is supposed to take both the TME as well as tumor heterogeneity into account. Although HNSCC patients are frequently studied in clinical trials, there is a lack of reliable prognostic biomarkers allowing a better stratification of individuals who might benefit from new concepts of targeted or immunotherapeutic strategies. Emerging evidence indicates that cancer stem cells (CSCs) are highly tumorigenic. Through the process of stemness, epithelial cells acquire an invasive phenotype contributing to metastasis and recurrence. Specific markers for CSC such as CD133 and CD44 expression and ALDH activity help to identify CSC in HNSCC. For the majority of patients, allocation of treatment regimens is simply based on histological diagnosis and on tumor location and disease staging (clinical risk assessments) rather than on specific or individual tumor biology. Hence there is an urgent need for tools to stratify HNSCC patients and pave the way for personalized therapeutic options. This work reviews the current literature on novel approaches in implementing three-dimensional (3D) HNSCC in vitro and in vivo tumor models in the clinical daily routine. Stem-cell based assays will be particularly discussed. Those models are highly anticipated to serve as a preclinical prediction platform for the evaluation of stable biomarkers and for therapeutic efficacy testing.