Miracle-dz/UniFAR-FTUs huggingface dataset:
Immunity, Infection, and the Zebrafish Clock

Circadian clocks are universally used to coordinate biological processes with the Earth’s 24-h solar day and are critical for the health and environmental success of an organism. Circadian rhythms in eukaryotes are driven by a cell-intrinsic transcription-translation feedback loop that controls daily oscillations in gene expression which regulate diverse physiological functions. ABSTRACT Circadian clocks are universally used to coordinate biological processes with the Earth’s 24-h solar day and are critical for the health and environmental success of an organism. Circadian rhythms in eukaryotes are driven by a cell-intrinsic transcription-translation feedback loop that controls daily oscillations in gene expression which regulate diverse physiological functions. Substantial evidence now exists demonstrating that immune activation and inflammatory responses during infection are under circadian control, however, the cellular mechanisms responsible for this are not well understood. The zebrafish (Danio rerio) is a powerful model organism to study vertebrate circadian biology and immune function. Zebrafish contain homologs of mammalian circadian clock genes which, to our current knowledge, function similarly to impart timekeeping ability. Consistent with studies in mammalian models, several studies in fish have now demonstrated a bidirectional relationship between the circadian clock and inflammation: the circadian clock regulates immune activity, and inflammation can alter circadian rhythms. This review summarizes our current understanding of the molecular mechanisms of the zebrafish clock and the bi-directional relationship between the circadian clock and inflammation in fish.
Cardiovascular implications of gestational diabetes mellitus for the mother and fetus/neonate

Taye et al. aimed to identify determinants of gestational diabetes mellitus (GDM) among pregnant women in Ethiopia. They demonstrated that a family history of diabetes mellitus (odds ratio [OR] 1.837; 95% confidence interval [CI] 1.06–3.18), a history of spontaneous abortion (OR 2.39; 95% CI 1.33–4.31), a history of stillbirth (OR 2.240; 95% CI 1.222–4.105) and a history of delivery of a macrosomic baby in the previous pregnancy (OR 1.99; 95% CI 1.157–3.43) were predictors of GDM. Due to the obesity pandemic, the prevalence of GDM has increased exponentially in the last few years. Maternal obesity not only makes GDM and pre-eclampsia during pregnancy more likely, but it also increases the risk of the mother developing metabolic syndrome and type 2 diabetes in later life. Besides the mother, GDM has implications for the fetus, including macrosomia, increased fetal cardiovascular disease and a high risk of metabolic and endocrine dysfunction in the offspring later in life. We have previously identified potential prognostic biomarkers of cardiovascular disease in large-for-gestational-age fetuses born to mothers with GDM. Serum cardiotrophin-1 (p< .001) and titin (p1⁄4 .023) concentrations were higher in large-for-gestational-age compared with appropriate-forgestational-age fetuses. Following subgroup analysis in the large-for-gestational-age group, serum cardiotrophin-1 concentrations were higher only in diabetic pregnancies. It was concluded that the determination of several cardiac biomarkers, such as cardiotrophin-1 and titin, in cord blood may have early prognostic value for later development of cardiovascular disease in macrosomic fetuses, particularly those derived from pregnancies with GDM. Besides cardiovascular diseases, GDM may also be associated with future offspring neurodevelopmental disorders. It was demonstrated that fetal serum brain-derived neurotrophic factor concentrations are down-regulated in fetuses exposed to GDM, independently of the fetal growth pattern. This may represent a candidate mechanism underlying the association between maternal GDM and later psychopathology in the offspring. Determining markers of GDM among pregnant women, as in the study by Taye et al., has important implications both for mothers, as well as for fetuses/neonates. Future studies should aim to assess cardiovascular risk early in life in order to optimize not only maternal, but also neonatal cardiovascular disease prevention measures in adult life. Transparency
Germline predisposition variants occur in myelodysplastic syndrome patients of all ages.

The frequency of pathogenic/likely pathogenic (P/LP) germline variants in myelodysplastic syndrome (MDS) patients diagnosed at or younger than 40 years old is 15 to 20%. However, there are no comprehensive studies assessing the frequency of such variants across the age spectrum. We performed augmented whole exome sequencing from peripheral blood of 404 MDS patients and their related donors prior to allogeneic hematopoietic stem cell transplantation. Single nucleotide and copy number variants in 233 genes were analyzed and interpreted. Germline status was established by the presence of a variant in the patient and related donor or for those seen previously only as germline alleles. We identified P/LP germline variants in 28 out of 404 MDS patients (7%) within all age deciles. Patients with P/LP variants were more likely to develop higher-grade MDS than those without (43% vs. 25%, p=0.04). There was no statistical difference in outcome parameters between patients with and without a germline variant, but the analysis was underpowered. P/LP variants in bone marrow failure syndrome genes were found in five patients under age 40, whereas variants in DDX41 (n=4), telomere biology disorder genes (n=2), and tumor predisposition genes (n=17) were found in patients over 40. If presumed germline variants were included, the yield of P/LP variants would increase to 11% and by adding suspicious variants of unknown significance, it would rise further to 12%. The high frequency of P/LP germline variants in our study supports comprehensive germline genetic testing for all MDS patients regardless of their age at diagnosis.
Phased Reconnaissance Approach to Documenting Landslides following the 2016 Central Italy Earthquakes

The 2016 Central Italy earthquake sequence caused numerous landslides over a large area in the Central Apennines. As a result, the Geotechnical Extreme Events Reconnaissance Association (GEER) organized post-earthquake reconnaissance missions to collect perishable data. Given the challenging conditions following the earthquakes, the GEER team implemented a phased reconnaissance approach. This paper illustrates this approach and how it was used to document the largest and most impactful seismically induced landslides. This phased approach relied upon satellite-based interferometric damage proxy maps, preliminary published reports of observed landslides, digital imaging from small unmanned aerial vehicles (UAVs), traditional manual observations, and terrestrial laser scanning. Data collected from the reconnoitered sites were used to develop orthophotos and meshed three-dimensional digital surface models. These products can provide valuable information such as accurate measurements of landslide ground movements in complex topographic geometries or boulder runout distances from rock falls. The paper describes three significant landslide case histories developed and documented with the phased approach: Nera Valley, Village of Pescara del Tronto, and near the villages of Crognaleto and Cervaro.
Intensive behavioural interventions based on applied behaviour analysis (ABA) for young children with autism: A cost-effectiveness analysis

Background The economic and social costs of autism are significant. This study evaluates the cost-effectiveness of early intensive Applied Behaviour Analysis (ABA)-based interventions for autistic pre-school children in the UK. Methods A de novo economic analysis was developed in Microsoft Excel comparing early intensive ABA-based interventions compared with treatment as usual (TAU). The analysis used 15.5-year time horizon, with costs and benefits discounted a 3.5%. The model structure was based on cohort structure to capture changes in adaptive behaviour and cognitive ability over time. The analysis was informed by an individual patient data (IPD) meta-analysis of available evidence. Results Adopting a public sector perspective, early intensive ABA-based therapies were associated with greater incremental costs and greater benefits. When pessimistic assumptions were made regarding the long-term effects of treatment incremental costs were £46,103 and incremental quality-adjusted life years (QALYs) were 0.24, resulting in an incremental cost-effectiveness ratio (ICER) of £189,122 per quality-adjusted life year (QALY). When optimistic assumptions were made about long-term effects, incremental costs were £39,233 with incremental benefits of 0.84 QALYs. The resulting ICER was £46,768 per QALY. Scenario analyses emphasised the importance of assumptions made regarding adult outcomes and type of school attended, both of which significantly affect the results of the analysis. Conclusions The results of this economic analysis suggest that early intensive ABA-based interventions are unlikely to represent value for money, based on a £20,000 to £30,000 per QALY threshold typically adopted to inform UK healthcare funding decisions. However, important gaps in the available evidence, limit the strength of the conclusions that can be drawn from the presented analysis. Further research, focusing on the trajectory of autistic children following intervention is likely to be highly beneficial to resolving some of these uncertainties.
Mitochondrial stress in advanced fibrosis and cirrhosis associated with chronic hepatitis B, chronic hepatitis C, or nonalcoholic steatohepatitis

Background and Aims: Hepatitis B virus (HBV) infection causes oxidative stress (OS) and alters mitochondria in experimental models. Our goal was to investigate whether HBV might alter liver mitochondria also in humans, and the resulting mitochondrial stress might account for the progression of fibrosis in chronic hepatitis B (CHB). Approach and Results: The study included 146 treatment‐naïve CHB mono‐infected patients. Patients with CHB and advanced fibrosis (AF) or cirrhosis (F3‐F4) were compared to patients with no/mild‐moderate fibrosis (F0‐F2). Patients with CHB were further compared to patients with chronic hepatitis C (CHC; n = 33), nonalcoholic steatohepatatis (NASH; n = 12), and healthy controls (n = 24). We detected oxidative damage to mitochondrial DNA (mtDNA), including mtDNA strand beaks, and identified multiple mtDNA deletions in patients with F3‐F4 as compared to patients with F0‐F2. Alterations in mitochondrial function, mitochondrial unfolded protein response, biogenesis, mitophagy, and liver inflammation were observed in patients with AF or cirrhosis associated with CHB, CHC, and NASH. In vitro, significant increases of the mitochondrial formation of superoxide and peroxynitrite as well as mtDNA damage, nitration of the mitochondrial respiratory chain complexes, and impairment of complex I occurred in HepG2 cells replicating HBV or transiently expressing hepatitits B virus X protein. mtDNA damage and complex I impairment were prevented with the superoxide‐scavenging Mito‐Tempo or with inducible nitric oxide synthase (iNOS)–specific inhibitor 1400 W. Conclusions: Our results emphasized the importance of mitochondrial OS, mtDNA damage, and associated alterations in mitochondrial function and dynamics in AF or cirrhosis in CHB and NASH. Mitochondria might be a target in drug development to stop fibrosis progression.
Lucky number 13: Association between center-specific chest wall stabilization volumes and patient outcomes

Analysis of 2019 TQIP data shows a favorable volume-outcome relationship at centers that performed chest wall stabilization. We identified a cut point of 13 annual surgeries per center to be associated with improved outcomes regardless of trauma center designation BACKGROUND Chest wall stabilization (CWS) improves outcomes for patients with chest wall injury (CWI). We hypothesized that patients treated at centers with higher annual CWS volumes experience superior outcomes. METHODS A retrospective study of adults with acute CWI undergoing surgical stabilization of rib or sternal fractures within the 2019 Trauma Quality Improvement Program database, excluding those with 24-hour mortality or any Abbreviated Injury Scale body region of six, was conducted. Hospitals were grouped in quartiles by annual CWS volume. Our primary outcome was a composite of in-hospital mortality, ventilator-associated pneumonia, acute respiratory distress syndrome, sepsis, and unplanned intubation or intensive care unit readmission. Regression was controlled for age, sex, Injury Severity Scale, flail chest, medical comorbidities, and Abbreviated Injury Scale chest. We performed cut-point analysis and compared patient outcomes from high- and low-volume centers. RESULTS We included 3,207 patients undergoing CWS at 430 hospitals with annual volumes ranging from 1 to 66. There were no differences between groups in age, sex, or Injury Severity Scale. Patients in the highest volume quartile (Q4) experienced significantly lower rates of the primary outcome (Q4, 14%; Q3, 18.4%; Q2, 17.4%; Q1, 22.1%) and significantly shorter hospital and intensive care unit lengths of stay. Q4 versus Q1 had lower adjusted odds of the primary outcome (odds ratio, 0.58; 95% confidence interval, 0.43–0.80). An optimal cut point of 12.5 procedures annually was used to define high- and low-volume centers. Patients treated at high-volume centers experienced significantly lower rates of the primary composite outcome, in-hospital mortality, and deep venous thrombosis with shorter lengths of stay and higher rates of home discharge. CONCLUSION Center-specific CWS volume is associated with superior in-hospital patient outcomes. These findings support efforts to establish CWI centers of excellence. Further investigation should explore the impact of center-specific volume on patient-reported outcomes including pain and postdischarge quality of life. LEVEL OF EVIDENCE Prognostic and Epidemiologic; Level III.
Selection against early flowering in geothermally heated soils is associated with pollen but not prey availability in a carnivorous plant

Abstract Premise In high‐latitude environments, plastic responses of phenology to increasing spring temperatures allow plants to extend growing seasons while avoiding late frosts. However, evolved plasticity might become maladaptive if climatic conditions change and spring temperatures no longer provide reliable cues for conditions important for fitness. Maladaptative phenological responses might be related to both abiotic factors and mismatches with interacting species. When mismatches arise, we expect selection to favor changes in phenology. Methods We combined observations along a soil temperature gradient in a geothermally heated area with pollen and prey supplementation experiments and examined how phenotypic selection on flowering time in the carnivorous plant Pinguicula vulgaris depends on soil temperature, and pollen and prey availability. Results Flowering advanced and fitness decreased with increasing soil temperature. However, in pollen‐supplemented plants, fitness instead increased with soil temperature. In heated soils, there was selection favoring later flowering, while earlier flowering was favored in unheated soils. This pattern remained also after artificially increasing pollen and prey availability. Conclusions Plant–pollinator mismatches can be an important reason why evolved plastic responses of flowering time to increasing spring temperatures become maladaptive under novel environmental conditions, and why there is selection to delay flowering. In our study, selection for later flowering remained after artificially increasing pollen availability, suggesting that abiotic factors also contribute to the observed selection. Identifying the factors that make evolved phenological responses maladaptive under novel conditions is fundamental for understanding and predicting evolutionary responses to climate warming.
The Effect of Exercise on Neurogenesis in the Brain.

BACKGROUND The connection between physical exercise and the brain has long been studied. The evidence showing that physical exercise plays a significant role on neurogenesis and cognitive function has primarily been based on research examining aerobic exercise. In this review, we described three exercise modalities: aerobic, anaerobic, and resistance exercise and their impact on brain plasticity and cognitive function. While each of these exercise modalities have been demonstrated to positively influence brain plasticity and cognitive function, the specific mechanism that stimulates these changes appear to differ to some degree between these training modalities. The effect of aerobic and anaerobic exercise appears to be primarily mediated by changes in expression of brain-derived neurotrophic factor (BDNF), lactate, vascular endothelial growth factor (VEGF), and several additional proteins within the brain. However, resistance exercise appears to influence brain plasticity by myokines such as irisin, insulin-growth factor-1 (IGF1), and BDNF that are secreted from skeletal tissue and stimulate neurogenesis within the brain. In addition to the various training modes, manipulation of various acute program variables such as intensity, volume, and rest intervals leads to numerous possible training paradigms that can provide a different stimulus for neurogenesis. This review focuses on the three primary training modes and their connection to neurogenesis and cognitive function.
A Genetic Interaction between the Core and NS3 Proteins of Hepatitis C Virus Is Essential for Production of Infectious Virus (cid:1) †

By analogy to other members of the Flaviviridae family, the hepatitis C virus (HCV) core protein is presumed to oligomerize to form the viral nucleocapsid, which encloses the single-stranded RNA genome. Core protein is directed to lipid droplets (LDs) by domain 2 (D2) of the protein, and this process is critical for virus production. Domain 1 (D1) of core is also important for infectious particle morphogenesis, although its precise contribution to this process is poorly understood. In this study, we mutated amino acids 64 to 75 within D1 of core and examined the ability of these mutants to produce infectious virus. We found that residues 64 to 66 are critical for generation of infectious progeny, whereas 67 to 75 were dispensable for this process. Further investigation of the defective 64 to 66 mutant (termed JFH1 T -64–66) revealed it to be incapable of producing infectious intracellular virions, suggesting a fault during HCV assembly. Furthermore, isopycnic gradient analyses revealed that JFH1 T -64–66 assembled dense intracellular species of core, presumably representing nucleocapsids. Thus, amino acids 64 to 66 are seemingly not involved in core oligomerization/nucleocapsid assembly. Passaging of JFH1 T
(2021). Physical activity and risk of atrial fibrillation in the general population: meta-analysis of 23 cohort studies involving about 2 million participants. European Journal of Epidemiology, 36(3), 259-274.

Regular physical activity is well established to be associated with reduced risk of cardiovascular disease outcomes. Whether physical activity is associated with the future risk of atrial fibrillation (AF) remains a controversy. Using a systematic review and meta-analysis of published observational cohort studies in general populations with at least one-year of follow-up, we aimed to evaluate the association between regular physical activity and the risk of AF. Relevant studies were sought from inception until October 2020 in MEDLINE, Embase, Web of Science, and manual search of relevant articles. Extracted relative risks (RRs) with 95% confidence intervals (CIs) for the maximum versus the minimal amount of physical activity groups were pooled using random-effects meta-analysis. Quality of the evidence was assessed by GRADE. A total of 23 unique observational cohort studies comprising of 1,930,725 participants and 45,839 AF cases were eligible. The pooled multivariable-adjusted RR (95% CI) for AF comparing the most physically active versus the least physically active groups was 0.99 (0.93–1.05). This association was modified by sex: an increased risk was observed in men: 1.20 (1.02–1.42), with a decreased risk in women: 0.91 (0.84–0.99). The quality of the evidence ranged from low to moderate. Pooled observational cohort studies suggest that the absence of associations reported between regular physical activity and AF risk in previous general population studies and their aggregate analyses could be driven by a sex-specific difference in the associations – an increased risk in men and a decreased risk in women.
Dietary Patterns and Oncological Morbidity in European and Mediterranean Countries

Purpose of the study is an analysis of the impact of per capita income, latitude and nutrition structure on the cancer incidence in European (Euro) and Mediterranean (Med) countries. Materials and Methods: Study design is observational. Nutrition structures for countries are presented as a general level of food consumption (g/person/ day) and as the percentage contribution of 4 blocks: animal products; grains and vegetables; fruit and drinks; alcoholic beverages. Results: In European countries, compared with the Med countries, the incidence of 7 cancer types in Euro countries depend on per capita income and latitude. In Euro countries, the incidence of 5 cancer types depends on “clean” per capita income. The incidence of 5 cancer types depends on “clean” latitude. The incidence of 7 cancer types in Euro and Mediterranean countries does not depend on per capita income, nor on latitude. The nutrition structure in Euro and Med countries depends on per capita income. The higher is per capita income in Euro countries, the higher is a share of animal products and alcoholic beverages in the nutrition structure. (p = 0.004). The level of macronutrients of animal in Euro countries is 1.5, 2.3 and 3.0 times higher than in Med countries and depends on per capita income (p = 0.001). Conclusions: The nutrition structure as a risk factor for cancer in the Euro and Med countries depends on per capita income. The composition and sources of macronutrients play an important role in the nutrition structure.
(Non-)Density Properties of Discrete Gabor Multipliers

—This paper is concerned with the possibility of ap- proximating arbitrary operators by multipliers for Gabor frames or more general Bessel sequences. It addresses the question of whether sets of multipliers (whose symbols come from prescribed function classes such as (cid:96) 2 ) constitute dense subsets of various spaces of operators (such as Hilbert-Schmidt class). We prove a number of negative results that show that in the discrete setting subspaces of multipliers are usually not dense and thus too small to guarantee arbitrary good approximation. This is in contrast to the continuous case.
Performance studies of R433A in a direct expansion solar-assisted heat pump

ABSTRACT Energy assessment of a simple direct expansion solar-assisted heat pump system has been experimentally assessed with R433A as a possible alternative to R22. An artificial neural network integrated genetic algorithm model was developed to assess the performance system. The data obtained from the experimentation at different ambient conditions are used as the training data for the ANN network. The back propagation learning mechanism with variants Lavenberg-Maguardt with 20 neurons in the hidden layer were used in modelling of ANN. The values obtained from the analysis using ANN are optimised further by integrating the ANN procedure with GA. The results indicated that R433A has 6.4% and 1% lower instantaneous compressor power consumption and heating capacity compared to R22. Energy performance ratio of R433A was found to be about 5.67% higher compared to R22. The results confirmed that R433A can be used as a possible alternative to R22 DX-SAHP systems.