Miracle-dz/UniFAR-FTUs huggingface dataset:
Acquisition of optimal TFH cell function is defined by specific molecular, positional, and TCR dynamic signatures

Significance We characterized the heterogeneity of human TFH cells at a cellular, molecular, functional, and positional level and revealed possible mechanistic links between relevant determinants of this heterogeneity. Linking the topology with specific molecular profile and function is a key aspect in the understanding of the role of particular TFH cell subsets in the pathogenesis of relevant diseases and the delivery of optimal help to GC B cells for the development of potent neutralizing antibodies. The development of follicular helper CD4 T (TFH) cells is a dynamic process resulting in a heterogenous pool of TFH subsets. However, the cellular and molecular determinants of this heterogeneity and the possible mechanistic links between them is not clear. We found that human TFH differentiation is associated with significant changes in phenotypic, chemokine, functional, metabolic and transcriptional profile. Furthermore, this differentiation was associated with distinct positioning to follicular proliferating B cells. Single-cell T cell receptor (TCR) clonotype analysis indicated the transitioning toward PD-1hiCD57hi phenotype. Furthermore, the differentiation of TFH cells was associated with significant reduction in TCR level and drastic changes in immunological synapse formation. TFH synapse lacks a tight cSMAC (central supra molecular activation Cluster) but displays the TCR in peripheral microclusters, which are potentially advantageous in the ability of germinal center (GC) B cells to receive necessary help. Our data reveal significant aspects of human TFH heterogeneity and suggest that the PD-1hiCD57hi TFH cells, in particular, are endowed with distinctive programming and spatial positioning for optimal GC B cell help.
Serum interleukin-30 level in patients with psoriasis and its correlation with psoriasis severity: a case-control study

Objectives To examine the serum levels of interleukin (IL)-30 in patients with psoriasis and evaluate the correlations with the Psoriasis Area and Severity Index (PASI). Methods Serum was collected from 26 patients with psoriasis and 26 healthy controls in a case–control setting, and the level of IL-30 was determined using an enzyme-linked immunosorbent assay. Statistical analysis of the IL-30 levels among groups and further correlation analyses of IL-30 levels with PASI scores were performed. Results A significant increase in the level of IL-30 in patients with psoriasis compared with healthy controls was observed. In addition, a positive correlation between the IL-30 concentration and PASI scores was found in patients with psoriasis. Conclusion IL-30 is presumably involved in the proliferation of epidermal cells during the development of psoriasis. Further studies with a larger number of participants are required to comprehensively elucidate the biological roles of IL-30 in the pathogenesis of psoriasis.
Consequences of space radiation on the brain and cardiovascular system

Abstract Staying longer in outer space will inevitably increase the health risks of astronauts due to the exposures to galactic cosmic rays and solar particle events. Exposure may pose a significant hazard to space flight crews not only during the mission but also later, when slow-developing adverse effects could finally become apparent. The body of literature examining ground-based outcomes in response to high-energy charged-particle radiation suggests differential effects in response to different particles and energies. Numerous animal and cellular models have repeatedly demonstrated the negative effects of high-energy charged-particle on the brain and cognitive function. However, research on the role of space radiation in potentiating cardiovascular dysfunction is still in its early stages. This review summarizes the available data from studies using ground-based animal models to evaluate the response of the brain and heart to the high-energy charged particles of GCR and SPE, addresses potential sex differences in these effects, and aims to highlight gaps in the current literature for future study.
Prognostic Value of Angiopoietin-like 4 in Patients with Acute Respiratory Distress Syndrome

ABSTRACT Background: Angiopoietin-like 4 (ANGPTL4) is a secreted glycoprotein that plays an important role in endothelial injury and the inflammatory response. Experimental models have implicated ANGPTL4 in acute respiratory distress syndrome (ARDS), but its impact on the progression of ARDS is unclear. Methods: Paired bronchoalveolar lavage fluid (BALF) and serum samples were obtained from patients with ARDS (n = 56) within 24 h of diagnosis and from control subjects (n = 32). ANGPTL4, angiopoietin-2, interleukin (IL)-6, and TNF-α levels were measured by magnetic Luminex assay. BALF albumin (BA) and serum albumin (SA) were evaluated by enzyme-linked immunosorbent assay. Results: BALF and serum ANGPTL4 concentrations were higher in patients with ARDS than in controls and were even higher in non-survivors than in survivors. The serum ANGPTL4 level was higher in indirect (extrapulmonary) ARDS than in direct (pulmonary) ARDS. Furthermore, BALF and serum ANGPTL4 levels correlated well with angiopoietin-2, IL-6, and TNF-α levels in BALF and serum. BALF ANGPTL4 was positively correlated with the BA/SA ratio (an indicator of pulmonary vascular permeability), and serum ANGPTL4 was associated with the severity of multiple organ dysfunction syndrome based on SOFA and APACHE II scores. Moreover, serum ANGPTL4 was better able to predict 28-day ARDS-related mortality (AUC 0.746, P < 0.01) than the APACHE II score or PaO2/FiO2 ratio. Serum ANGPTL4 was identified as an independent risk factor for mortality in a univariate Cox regression model (P < 0.001). Conclusion: ANGPTL4 levels were elevated in patients with ARDS and significantly correlated with disease severity and mortality. ANGPTL4 may be a novel prognostic biomarker in ARDS.
Quantitative relations between BOLD responses, cortical energetics and impulse firing across cortical depth

The blood oxygen level‐dependent (BOLD) functional magnetic resonance imaging (fMRI) signal arises as a consequence of changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) that in turn are modulated by changes in neural activity. Recent advances in imaging have achieved sub‐millimetre resolution and allowed investigation of the BOLD response as a function of cortical depth. Here, we adapt our previous theory relating the BOLD signal to neural activity to produce a quantitative model that incorporates venous blood draining between cortical layers. The adjustable inputs to the model are the neural activity and a parameter governing this blood draining. A three‐layer version for transient neural inputs and a multi‐layer version for constant or tonic neural inputs are able to account for a variety of experimental results, including negative BOLD signals.
Association of chronic pain with comorbidities and health care utilization: a retrospective cohort study using health administrative data.

ABSTRACT Health administrative data provide a potentially robust information source regarding the substantial burden chronic pain exerts on individuals and the health care system. This study aimed to use health administrative data to estimate comorbidity prevalence and annual health care utilization associated with chronic pain in Newfoundland and Labrador, Canada. Applying the validated Chronic Pain Algorithm to provincial Fee-for-Service Physician Claims File data (1999-2009) established the Chronic Pain (n = 184,580) and No Chronic Pain (n = 320,113) comparator groups. Applying the Canadian Chronic Disease Surveillance System coding algorithms to Claims File and Provincial Discharge Abstract Data (1999-2009) determined the prevalence of 16 comorbidities. The 2009/2010 risk and person-year rate of physician and diagnostic imaging visits and hospital admissions were calculated and adjusted using the robust Poisson model with log link function (risks) and negative binomial model (rates). Results indicated a significantly higher prevalence of all comorbidities and up to 4 times the odds of multimorbidity in the Chronic Pain Group (P-value < 0.001). Chronic Pain Group members accounted for 58.8% of all physician visits, 57.6% of all diagnostic imaging visits, and 54.2% of all hospital admissions in 2009/2010, but only 12% to 16% of these were for pain-related conditions as per recorded diagnostic codes. The Chronic Pain Group had significantly higher rates of physician visits and high-cost hospital admission/diagnostic imaging visits (P-value < 0.001) when adjusted for demographics and comorbidities. Observations made using this methodology supported that people identified as having chronic pain have higher prevalence of comorbidities and use significantly more publicly funded health services.
Humanoid socially assistive robots in dementia care: a qualitative study about expectations of caregivers and dementia trainers

Abstract Objective To examine the expectations of informal caregivers, nurses, and dementia trainers regarding the support of (physical and psychosocial) human needs by humanoid social assistive robots (SARs) in dementia care. Methods A qualitative study was conducted with 11 homogeneous focus groups of informal caregivers, nurses and dementia trainers providing dementia care at home, in adult daycare centers, or in nursing homes. A qualitative content analysis was performed using a concept- and data-driven coding frame. Results Focus group discussions with 52 individuals were held. Participants reported mostly positive expectations and stated that SARs could offer potential support in all components of human needs, especially in avoiding danger (e.g. recognise danger, organise help), communication/contact with others (e.g. enable telephone calls, provide company), daily activities (e.g. remind of appointments, household obligations), recreational activities (e.g. provide music), eating/drinking (e.g. help cook), and mobility/body posture (e.g. give reminders/instructions for physical exercise). Participants also mentioned some negative expectations in all human needs, predominantly in communication/contact with others (e.g. loss of interpersonal interaction) and avoiding danger (e.g. scepticism regarding emergencies). Conclusion Participants stated that SARs had great potential to provide assistance in dementia care, especially by reminding, motivating/encouraging and instructing people with dementia. Informal caregivers and nurses also considered them as useful supportive devices for themselves. However, participants also mentioned negative expectations, especially in communication/contact with others and avoiding danger. These findings demonstrate the support caregivers and dementia trainers expect from humanoid SARs and may contribute to their optimisation for dementia care.
Numerical and experimental characterization of splitter blade impact on pump as turbine performance

Several rivers and streams are available in Africa and Asian regions with great potentials not applicable for constructing large hydropower dams but feasible for small and mini hydro generation. This study strive for investigating the impact of splitter blade on pump as turbine performance considering different speed and flow rates. Two specific centrifugal pump models one with six blades without splitter and another with four blades and four splitters were used for the study. The inlet diameter and outlet diameters of both impellers were 104 mm/116 mm, and 160 mm respectively at a designed flow rate Q = 12.5 m3/h, head H = 16 m, rotational speed n = 1450 rpm and efficiency of 56%, outlet impeller width of 0.006 m, a blade outlet angle of 30° was used for the study. CFD simulations were conducted with the use of k-ε turbulence model. The influence of splitter blade position on the performance of pump as turbine in the selected specific pumps with and without splitter blades has been investigated both experimentally and numerically at three different flow rates and rotational speed. The simulated data were in good agreement with the experimental results, the maximum deviation error between the CFD and test for each model are 5.6%, 2.6%, for the head and efficiency; 7.5% and 3.6% at different flow conditions.
Radicicol Inhibits Chikungunya Virus Replication by Targeting Nonstructural Protein 2

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes a debilitating febrile illness characterized by persistent muscle and joint pain. The widespread distribution of transmission-competent vectors, Aedes species mosquitoes, indicates the potential risk of large-scale epidemics with high attack rates that can severely impact public health globally. ABSTRACT Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes a debilitating febrile illness characterized by persistent muscle and joint pain. The widespread distribution of transmission-competent vectors, Aedes species mosquitoes, indicates the potential risk of large-scale epidemics with high attack rates that can severely impact public health globally. Despite this, currently, there are no antivirals available for the treatment of CHIKV infections. Thus, we aimed to identify potential drug candidates by screening a chemical library using a cytopathic effect-based high-throughput screening assay. As a result, we identified radicicol, a heat shock protein 90 (Hsp90) inhibitor that effectively suppressed CHIKV replication by blocking the synthesis of both positive- and negative-strand viral RNA as well as expression of viral proteins. Interestingly, selection for viral drug-resistant variants and mutational studies revealed nonstructural protein 2 (nsP2) as a putative molecular target of radicicol. Moreover, coimmunoprecipitation and in silico modeling analyses determined that G641D mutation in the methyltransferase (MT)-like domain of nsP2 is essential for its interaction with cytoplasmic Hsp90β chaperone. Our findings collectively support the potential application of radicicol as an anti-CHIKV agent. The detailed study of the underlying mechanism of action further contributes to our understanding of virus-host interactions for novel therapeutics against CHIKV infection.
An artificial intelligence deep learning model for identification of small bowel obstruction on plain abdominal radiographs

Objectives: Small bowel obstruction is a common surgical emergency which can lead to bowel necrosis, perforation and death. Plain abdominal X-rays are frequently used as a first-line test but the availability of immediate expert radiological review is variable. The aim was to investigate the feasibility of using a deep learning model for automated identification of small bowel obstruction. Methods: A total of 990 plain abdominal radiographs were collected, 445 with normal findings and 445 demonstrating small bowel obstruction. The images were labelled using the radiology reports, subsequent CT scans, surgical operation notes and enhanced radiological review. The data were used to develop a predictive model comprising an ensemble of five convolutional neural networks trained using transfer learning. Results: The performance of the model was excellent with an area under the receiver operator curve (AUC) of 0.961, corresponding to sensitivity and specificity of 91 and 93% respectively. Conclusion: Deep learning can be used to identify small bowel obstruction on plain radiographs with a high degree of accuracy. A system such as this could be used to alert clinicians to the presence of urgent findings with the potential for expedited clinical review and improved patient outcomes. Advances in knowledge: This paper describes a novel labelling method using composite clinical follow-up and demonstrates that ensemble models can be used effectively in medical imaging tasks. It also provides evidence that deep learning methods can be used to identify small bowel obstruction with high accuracy.
Therapeutic Inertia in the Management of Moderate-to-Severe Plaque Psoriasis in Adolescents

Society for Publication of Acta Dermato-Venereologica 1https://doi.org/10.2340/00015555-3813 Psoriasis is one of the most common chronic inflammatory skin diseases, the management of which has been revolutionized over the past decade by the development of biotherapies (1, 2) Symptoms occur in 20–30% of patients before the age of 18 years (3). When considered mild, psoriasis in children and adolescents may be managed with topical treatments. For moderate-to-severe psoriasis, guidelines are rare and poorly applied, and management is frequently delayed (4–6). Therapeutic inertia is the failure to initiate or intensify treatment in a patient even when recommended (7, 8). Already evaluated in chronic diseases (e.g. diabetes, multiple sclerosis, hypertension), this phenomenon is rarely considered in dermatology (9, 10). The aim of this study was to investigate therapeutic inertia among dermatologists treating moderate-to-severe plaque psoriasis in adolescents.
Systematic Assessment of Medical Diagnoses Preceding the First Diagnosis of Multiple Sclerosis

Objective To explore the occurrence of diseases and symptoms in the 5 years before diagnosis in patients with multiple sclerosis (MS) in a case-control study. Methods Using ambulatory claims data, we systematically assessed differences in the occurrence of diseases and symptoms in the 5 years before first diagnosis in patients with MS (n = 10,262) compared to patients with 2 other autoimmune diseases, Crohn disease (n = 15,502) and psoriasis (n = 98,432), and individuals without these diseases (n = 73,430). Results Forty-three ICD-10 codes were recorded more frequently for patients with MS before diagnosis compared to controls without autoimmune disease. Many of these findings were confirmed in a comparison to the other control groups. A high proportion of these ICD-10 codes represent symptoms suggestive of demyelinating events or other neurologic diagnoses. In a sensitivity analysis excluding patients with such recordings before first diagnosis, no association remained significant. Seven ICD-10 codes were associated with lower odds ratios of MS, 4 of which represent upper respiratory tract infections. Here, the relations with MS were even more pronounced in the sensitivity analysis. Conclusions Our analyses suggest that patients with MS are frequently not diagnosed at their first demyelinating event but often years later. Symptoms and physician encounters before MS diagnosis seem to be related to already ongoing disease rather than a prodrome. The observed association of upper respiratory tract infections with lower odds ratios of MS diagnosis suggests a link between protection from infection and MS that, however, needs to be validated and further investigated.
Ecophysiological steps of marine adaptation in extant and extinct non‐avian tetrapods

Marine reptiles and mammals are phylogenetically so distant from each other that their marine adaptations are rarely compared directly. We reviewed ecophysiological features in extant non‐avian marine tetrapods representing 31 marine colonizations to test whether there is a common pattern across higher taxonomic groups, such as mammals and reptiles. Marine adaptations in tetrapods can be roughly divided into aquatic and haline adaptations, each of which seems to follow a sequence of three steps. In combination, these six categories exhibit five steps of marine adaptation that apply across all clades except snakes: Step M1, incipient use of marine resources; Step M2, direct feeding in the saline sea; Step M3, water balance maintenance without terrestrial fresh water; Step M4, minimized terrestrial travel and loss of terrestrial feeding; and Step M5, loss of terrestrial thermoregulation and fur/plumage. Acquisition of viviparity is not included because there is no known case where viviparity evolved after a tetrapod lineage colonized the sea. A similar sequence is found in snakes but with the haline adaptation step (Step M3) lagging behind aquatic adaptation (haline adaptation is Step S5 in snakes), most likely because their unique method of water balance maintenance requires a supply of fresh water. The same constraint may limit the maximum body size of fully marine snakes. Steps M4 and M5 in all taxa except snakes are associated with skeletal adaptations that are mechanistically linked to relevant ecophysiological features, allowing assessment of marine adaptation steps in some fossil marine tetrapods. We identified four fossil clades containing members that reached Step M5 outside of stem whales, pinnipeds, sea cows and sea turtles, namely Eosauropterygia, Ichthyosauromorpha, Mosasauroidea, and Thalattosuchia, while five other clades reached Step M4: Saurosphargidae, Placodontia, Dinocephalosaurus, Desmostylia, and Odontochelys. Clades reaching Steps M4 and M5, both extant and extinct, appear to have higher species diversity than those only reaching Steps M1 to M3, while the total number of clades is higher for the earlier steps. This suggests that marine colonizers only diversified greatly after they minimized their use of terrestrial resources, with many lineages not reaching these advanced steps. Historical patterns suggest that a clade does not advance to Steps M4 and M5 unless these steps are reached early in the evolution of the clade. Intermediate forms before a clade reached Steps M4 and M5 tend to become extinct without leaving extant descendants or fossil evidence. This makes it difficult to reconstruct the evolutionary history of marine adaptation in many clades. Clades that reached Steps M4 and M5 tend to last longer than other marine tetrapod clades, sometimes for more than 100 million years.
Identifying Medicare beneficiaries with dementia

No data exist regarding the validity of International Classification of Disease (ICD)‐10 dementia diagnoses against a clinician‐adjudicated reference standard within Medicare claims data. We examined the accuracy of claims‐based diagnoses with respect to expert clinician adjudication using a novel database with individual‐level linkages between electronic health record (EHR) and claims.
Management of Salivary Gland Malignancy: ASCO Guideline

PURPOSE To provide evidence-based recommendations for practicing physicians and other healthcare providers on the management of salivary gland malignancy. METHODS ASCO convened an Expert Panel of medical oncology, surgical oncology, radiation oncology, neuroradiology, pathology, and patient advocacy experts to conduct a literature search, which included systematic reviews, meta-analyses, randomized controlled trials, and prospective and retrospective comparative observational studies published from 2000 through 2020. Outcomes of interest included survival, diagnostic accuracy, disease recurrence, and quality of life. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS The literature search identified 293 relevant studies to inform the evidence base for this guideline. Six main clinical questions were addressed, which included subquestions on preoperative evaluations, surgical diagnostic and therapeutic procedures, appropriate radiotherapy techniques, the role of systemic therapy, and follow-up evaluations. RECOMMENDATIONS When possible, evidence-based recommendations were developed to address the diagnosis and appropriate preoperative evaluations for patients with a salivary gland malignancy, therapeutic procedures, and appropriate treatment options in various salivary gland histologies. Additional information is available at www.asco. org/head-neck-cancer-guidelines.