Miracle-dz/UniFAR-FTUs huggingface dataset:
Muscle stem cells contribute to long‐term tissue repletion following surgical sepsis

Over the past decade, advances in sepsis identification and management have resulted in decreased sepsis mortality. This increase in survivorship has highlighted a new clinical obstacle: chronic critical illness (CCI), for which there are no effective treatment options. Up to half of sepsis survivors suffer from CCI, which can include multi‐organ dysfunction, chronic inflammation, muscle wasting, physical and mental disabilities, and enhanced frailty. These symptoms prevent survivors from returning to regular day‐to‐day activities and are directly associated with poor quality of life.
The interactions of SARS-CoV-2 with cocirculating pathogens: Epidemiological implications and current knowledge gaps

Despite the availability of effective vaccines, the persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suggests that cocirculation with other pathogens and resulting multiepidemics (of, for example, COVID-19 and influenza) may become increasingly frequent. To better forecast and control the risk of such multiepidemics, it is essential to elucidate the potential interactions of SARS-CoV-2 with other pathogens; these interactions, however, remain poorly defined. Here, we aimed to review the current body of evidence about SARS-CoV-2 interactions. Our review is structured in four parts. To study pathogen interactions in a systematic and comprehensive way, we first developed a general framework to capture their major components: sign (either negative for antagonistic interactions or positive for synergistic interactions), strength (i.e., magnitude of the interaction), symmetry (describing whether the interaction depends on the order of infection of interacting pathogens), duration (describing whether the interaction is short-lived or long-lived), and mechanism (e.g., whether interaction modifies susceptibility to infection, transmissibility of infection, or severity of disease). Second, we reviewed the experimental evidence from animal models about SARS-CoV-2 interactions. Of the 14 studies identified, 11 focused on the outcomes of coinfection with nonattenuated influenza A viruses (IAVs), and 3 with other pathogens. The 11 studies on IAV used different designs and animal models (ferrets, hamsters, and mice) but generally demonstrated that coinfection increased disease severity compared with either monoinfection. By contrast, the effect of coinfection on the viral load of either virus was variable and inconsistent across studies. Third, we reviewed the epidemiological evidence about SARS-CoV-2 interactions in human populations. Although numerous studies were identified, only a few were specifically designed to infer interaction, and many were prone to multiple biases, including confounding. Nevertheless, their results suggested that influenza and pneumococcal conjugate vaccinations were associated with a reduced risk of SARS-CoV-2 infection. Finally, fourth, we formulated simple transmission models of SARS-CoV-2 cocirculation with an epidemic viral pathogen or an endemic bacterial pathogen, showing how they can naturally incorporate the proposed framework. More generally, we argue that such models, when designed with an integrative and multidisciplinary perspective, will be invaluable tools to resolve the substantial uncertainties that remain about SARS-CoV-2 interactions.
Chemotherapy with the use of next‐generation tyrosine kinase inhibitors based on measurable residual disease has the potential to avoid hematopoietic stem cell transplantation in treatment for adults with Philadelphia chromosome–positive acute lymphoblastic leukemia

Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) as postremission treatment is recommended for Philadelphia‐positive acute lymphoblastic leukemia (Ph+ ALL) in current guidelines. However, comparisons of later generation tyrosine kinase inhibitors (TKIs) plus chemotherapy with allo‐HSCT have yielded similar outcomes. This meta‐analysis was performed to evaluate allo‐HSCT in first complete remission (CR1) versus chemotherapy for adult Ph+ ALL in the TKI era.
Seasonal variation in blood pressure control across US health systems

Objective: We aimed to characterize seasonal variation in US population-based blood pressure (BP) control and BP-related metrics and evaluate the association between outdoor temperature and BP control variation. Methods: We queried electronic health records (EHRs) from 26 health systems, representing 21 states, to summarize BP metrics by quarters of 12-month periods from January 2017 to March 2020. Patients with at least one ambulatory visit during the measurement period and a hypertension diagnosis during the first 6 months or prior to the measurement period were included. Changes in BP control, BP improvement, medication intensification, average SBP reduction after medication intensification across quarters and association with outdoor temperature were analyzed using weighted generalized linear models with repeated measures. Results: Among 1 818 041 people with hypertension, the majority were more than 65 years of age (52.2%), female (52.1%), white non-Hispanic (69.8%) and had stage 1/2 hypertension (64.8%). Overall, BP control and process metrics were highest in quarters 2 and 3, and lowest in quarters 1 and 4. Quarter 2 had the highest percentage of improved BP (31.95 ± 0.90%) and average SBP reduction after medication intensification (16 ± 0.23 mmHg). Quarter 3 had the highest percentage of BP controlled (62.25 ± 2.55%) and lowest with medication intensification (9.73 ± 0.60%). Results were largely consistent in adjusted models. Average temperature was associated with BP control metrics in unadjusted models, but associations were attenuated following adjustment. Conclusion: In this large, national, EHR-based study, BP control and BP-related process metrics improved during spring/summer months, but outdoor temperature was not associated with performance following adjustment for potential confounders.
PARTICLE DENSITIES WITHIN THE ACCELERATION REGION OF A SOLAR FLARE

The limb flare SOL2012-07-19T05:58 (M7.7) provides the best example of a non-thermal above-the-loop-top hard X-ray source with simultaneous observations by the Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI) and the Atmospheric Imaging Assembly on board the Solar Dynamic Observatory. By combining the two sets of observations, we present the first direct measurement of the thermal proton density and non-thermal electron density within the above-the-loop-top source where particle acceleration occurs. We find that both densities are of the same order of magnitude of a few times 109 cm−3, about 30 times lower than the density in the underlying thermal flare loops. The equal densities indicate that the entire electron population within the above-the-loop-top source is energized. While the derived densities depend on the unknown source depth and filling factor, the ratio of these two densities does not. Within the uncertainties, the ratio is one for a low energy cutoff of the non-thermal electron spectrum between 10 and 15 keV. RHESSI observations only constrain the cutoff energy to below ∼15 keV, leaving the spectral shape of the electrons within the above-the-loop-top source at lower energies unknown. Nevertheless, these robust results strongly corroborate earlier findings that the above-the-loop-top source is the acceleration region where a bulk energization process acts on all electrons.
Early development of respiratory motor circuits in larval zebrafish (Danio rerio)

Rhythm‐generating circuits in the vertebrate hindbrain form synaptic connections with cranial and spinal motor neurons, to generate coordinated, patterned respiratory behaviors. Zebrafish provide a uniquely tractable model system to investigate the earliest stages in respiratory motor circuit development in vivo. In larval zebrafish, respiratory behaviors are carried out by muscles innervated by cranial motor neurons—including the facial branchiomotor neurons (FBMNs), which innervate muscles that move the jaw, buccal cavity, and operculum. However, it is unclear when FBMNs first receive functional synaptic input from respiratory pattern‐generating neurons, and how the functional output of the respiratory motor circuit changes across larval development. In the current study, we used behavior and calcium imaging to determine how early FBMNs receive functional synaptic inputs from respiratory pattern‐generating networks in larval zebrafish. Zebrafish exhibited patterned operculum movements by 3 days postfertilization (dpf), though this behavior became more consistent at 4 and 5 dpf. Also by 3dpf, FBMNs fell into two distinct categories (“rhythmic” and “nonrhythmic”), based on patterns of neural activity. These two neuron categories were arranged differently along the dorsoventral axis, demonstrating that FBMNs have already established dorsoventral topography by 3 dpf. Finally, operculum movements were coordinated with pectoral fin movements at 3 dpf, indicating that the operculum behavioral pattern was driven by synaptic input. Taken together, this evidence suggests that FBMNs begin to receive initial synaptic input from a functional respiratory central pattern generator at or prior to 3 dpf. Future studies will use this model to study mechanisms of normal and abnormal respiratory circuit development.
Evolution of antibody titers after two doses of mRNA Pfizer-BioNTech vaccine and effect of the third dose in nursing home residents

Objectives We evaluated the IgG antibody titer against SARS-CoV-2 in 196 residents of a Spanish nursing home after the second dose of the BNT162b2 vaccine and the evolution of this titer over time. The role of the third dose of the vaccine on immune-response is also analysed in 115 of participants. Methods Vaccine response was evaluated 1, 3 and 6 months after second dose of Pfizer-BioNTech COVID-19 Vaccine and 30 days after booster vaccination. Total anti-RBD (receptor binding domain) IgG immunoglobulins were measured to assess response. Six month after the second dose of vaccine and previously to the booster, T-cell response was also measured in 24 resident with different antibody levels. T-spot Discovery SARS-CoV-2 kit was used to identify cellular immunogenicity. Results As high as 99% of residents demonstrated a positive serological response after second dose. Only two patients showed no serologic response, two men without records of previous SARS-CoV-2 infection. A higher immune response was associated with prior SARS-CoV-2 infection regardless of the gender or age. The anti-S IgG titers decreased significantly in almost all the participants (98.5%) after six months of vaccination whatever previous COVID-infection. The third dose of vaccine increased antibody titers in all patients, although initial vaccination values were not restored in the majority of cases. Conclusion The main conclusion of the study is that vaccine resulted in good immunogenicity in this vulnerable population. Nevertheless more data are needed on the long-term maintenance of antibody response after booster vaccination.
The effect of omega-3 polyunsaturated fatty acid intake on blood levels of omega-3s in people with chronic atherosclerotic disease: a systematic review

Abstract Context Atherosclerosis is a systemic pro-inflammatory and pro-oxidative disease, accounting for approximately a third of deaths globally. It has been proposed that omega-3s, through their antioxidant and anti-inflammatory properties, mitigate atherosclerotic disease progression. However, due to the systemic pro-inflammatory and pro-oxidative state of atherosclerosis, it is proposed that patients with atherosclerotic disease may have higher omega-3 requirements than the average requirement, due to increased nutrient utilization in anti-inflammatory and anti-oxidant processes. Objective The aim of this review was to determine what dose and duration of omega-3 supplementation is required to reach a therapeutic blood level of omega-3s (eicosapentaenoic acid ≥150 µg/mL or omega-3 index ≥8%) in people with chronic atherosclerotic disease. Data Sources This systematic review comprehensively searched MEDLINE, Emcare, Scopus, and CINAHL using key search terms for atherosclerotic disease, omega-3, supplementation, and blood levels of omega-3s. Data Extraction Two reviewers independently screened 529 randomized controlled trials (RCTs) supplementing omega-3s in patients with chronic atherosclerotic disease. Data Analysis In total, 25 journal articles from 17 original RCTs were included and assessed quantitatively. Supplementation at 1.8 g to 3.4 g per day for a 3-month–6-month duration, and at 4.4 g and above for as little as 1 month–6 months were identified as the most effective dosage ranges for increasing blood levels of omega-3s to therapeutic levels in people with atherosclerotic disease. Conclusions Consideration should be given to routine omega-3 supplementation and to increasing the omega-3 dietary recommendations and upper limits of daily intake to improve clinical outcomes and reduce the risk of cardiac mortality in this population.
Massive Somatic and Germline Chromosomal Integrations of Polydnaviruses in Lepidopterans

Abstract Increasing numbers of horizontal transfer (HT) of genes and transposable elements are reported in insects. Yet the mechanisms underlying these transfers remain unknown. Here we first quantify and characterize the patterns of chromosomal integration of the polydnavirus (PDV) encoded by the Campopleginae Hyposoter didymator parasitoid wasp (HdIV) in somatic cells of parasitized fall armyworm (Spodoptera frugiperda). PDVs are domesticated viruses injected by wasps together with their eggs into their hosts in order to facilitate the development of wasp larvae. We found that six HdIV DNA circles integrate into the genome of host somatic cells. Each host haploid genome suffers between 23 and 40 integration events (IEs) on average 72 h post-parasitism. Almost all IEs are mediated by DNA double-strand breaks occurring in the host integration motif (HIM) of HdIV circles. We show that despite their independent evolutionary origins, PDV from both Campopleginae and Braconidae wasps use remarkably similar mechanisms for chromosomal integration. Next, our similarity search performed on 775 genomes reveals that PDVs of both Campopleginae and Braconidae wasps have recurrently colonized the germline of dozens of lepidopteran species through the same mechanisms they use to integrate into somatic host chromosomes during parasitism. We found evidence of HIM-mediated HT of PDV DNA circles in no less than 124 species belonging to 15 lepidopteran families. Thus, this mechanism underlies a major route of HT of genetic material from wasps to lepidopterans with likely important consequences on lepidopterans.
Systematically analysing the acceptability of pig farming systems with different animal welfare levels when considering intra-sustainability trade-offs: Are citizens willing to compromise?

In recent years, intensive pig husbandry has been subject to increasing public criticism, including a clear demand for more animal-friendly housing systems in many countries. However, such systems are associated with trade-offs at the expense of other sustainability domains, which challenges implementation and makes prioritization necessary. Overall, research is scarce that systematically analyses citizens’ evaluation of different pig housing systems and associated trade-offs. Given the ongoing transformation process of future livestock systems that meet social demands, it is crucial to include public attitudes. We therefore assessed how citizens evaluate different pig housing systems and whether they are willing to compromise animal welfare in trade-off situations. We conducted an online survey with 1,038 German citizens using quota and split sampling in a picture-based survey design. Participants were asked to evaluate several housing systems with different animal welfare levels and associated trade-offs based on an either positive (‘free-range’ in split 1) or negative (‘indoor housing with fully slatted floors’ in split 2) reference system. Initial acceptability was highest for the ‘free-range’ system, followed by ‘indoor housing with straw bedding and outdoor access’, ‘indoor housing with straw bedding’, and ‘indoor housing with fully slatted floors’, with only the latter being clearly not acceptable for many. Overall acceptability was higher with a positive rather than a negative reference system. When confronted with several trade-off situations, participants became uncertain and temporarily adjusted their evaluations. Thereby participants were most likely to trade off housing conditions against animal or human health rather than against climate protection or a lower product price. Nevertheless, a final evaluation demonstrated that participants did not fundamentally change their initial attitudes. Our findings provide evidence that citizens’ desire for good housing conditions is relatively stable, but they are willing to compromise at the expense of animal welfare up to a moderate level.
Virtuous victims: Disability claimants who over- and under-report

Abstract Objective: The present study was the first to investigate the test performance and symptom reports of individuals who engage in both over-reporting (i.e., exaggerating or fabricating symptoms) and under-reporting (i.e., exaggerating positive qualities or denying shortcomings) in the context of a forensic evaluation. We focused on comparing individuals who over- and under-reported (OR + UR) with those who only over-reported (OR-only) on the MMPI-3. Method: Using a disability claimant sample referred for comprehensive psychological evaluations (n = 848), the present study first determined the rates of possible over-reporting (MMPI-3 F ≥ 75 T, Fp ≥ 70 T, Fs ≥ 100 T, or FBS or RBS ≥ 90 T) with (n = 42) and without (n = 332) under-reporting (L ≥ 65 T). Next, we examined group mean differences on MMPI-3 substantive scale scores and scores on several additional measures completed by the disability claimant sample during their evaluation. Results: The small group of individuals identified as both over-reporting and under-reporting (OR + UR) scored meaningfully higher than the OR-only group on several over- and under-reporting symptom validity tests, as well as on measures of emotional and cognitive/somatic complaints, but lower on externalizing measures. The OR + UR group also performed significantly worse than the OR-only group on several performance validity tests and measures of cognitive ability. Conclusions: The present study indicated that disability claimants who engage in simultaneous over- and under-reporting portray themselves as having greater levels of dysfunction but fewer externalizing tendencies relative to claimants who only over-report; however, these portrayals are likely less accurate reflections of their true functioning.
Investigation of the Relevant Factors in the Complexity of Chronic Low Back Pain Patients With a Physiotherapy Prescription

Objective Chronic low back pain (CLBP) is the leading cause of disability worldwide, and several factors have been proposed as potential causes or cofactors. The aim of this study was to explore their direct and indirect relations to understand CLBP and identify relevant rehabilitation targets. Methods A total of 119 patients with CLBP and 117 chronic pain–free individuals were assessed. A network analysis approach was used to explore the complexity of CLBP by assessing the relations between pain intensity, disability, functionality (physical, social, and psychological), age, body mass index, and education level. Results The network analysis revealed the independence of pain and disability related to CLBP from age, sex, and body mass index. Crucially, pain intensity and disability are directly and strongly connected in chronic pain–free individuals, but not in patients with CLBP. Psychosocial functioning is related to pain intensity and disability indirectly through the mediation of one’s general health perception and perceived physical functionality. Conclusion Clinicians should pay more attention to perceived physical functionality and psychosocial factors as they are tightly linked to CLBP. Indeed, pain intensity seems a suboptimal rehabilitation target. This study suggests that a biopsychosocial approach is much needed to investigate CLBP, but it also warns against overestimating the direct impact of each potential contributor. To Claim CME Credits Complete the self-assessment activity and evaluation online at http://www.physiatry. org/JournalCME CME Objectives Upon completion of this article, the reader should be able to: (1) Recognize the relation of pain intensity, disability, and loss of function in patients with CLBP; (2) Determine the impact of the most common biological and psychosocial factors in addressing the assessment of chronic back pain patients; and (3) Enhance confidence in selecting the relevant outcomes for the assessment of patients with CLBP following a multidimensional assessment. Level Advanced Accreditation The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.
Immature platelets in COVID-19

Abstract Platelets play a critical role in immune response. Coronavirus disease 2019 (COVID-19) patients with a severe course often show pathological coagulation parameters including thrombocytopenia, and at the same time the proportion of immature platelets increases. In this study, the platelet count and the immature platelet fraction (IPF) of hospitalized patients with different oxygenation requirements was investigated daily over a course of 40 days. In addition, the platelet function of COVID-19 patients was analyzed. It was found that the number of platelets in patients with the most severe course (intubation and extracorporeal membrane oxygenation (ECMO)) was significantly lower (111.5 ∙ 106 /mL) than in the other groups (mild (no intubation, no ECMO): 203.5 ∙ 106 /mL, p < . 0001, moderate (intubation, no ECMO): 208.0 ∙ 106 /mL, p < . 0001). IPF tended to be elevated (10.9%). Platelet function was reduced. Differentiation by outcome revealed that the deceased patients had a highly significant lower platelet count and higher IPF (97.3 ∙ 106 /mL, p < .0001, 12.2%, p = .0003). Plain Language Summary What is the context? Pathological coagulation is a feature of severe cases of COVID-19, with both bleeding complications and thrombosis. Patients with severe COVID-19 are frequently treated with extracorporeal membrane oxygenation (ECMO), which is often associated with bleeding complications. Platelets play an important role in blood clotting. The proportion of immature platelets has been characterized as hyperreactive and associated with high prothrombotic activity. In addition, they are discussed as predictors of COVID-19 disease severity. What is new? In grading the severity of disease in our patient cohort, we consider the required oxygenation measures. Thus, the focus is on severe cases requiring intubation and ECMO compared to moderate (intubation, no ECMO) and mild (no intubation, no ECMO) cases. What is the impact? This study focuses on severely ill patients who require ECMO treatment. Therefore, this study provides further evidence to use immature platelet fraction to predict the outcome of severe COVID-19 courses.