Miracle-dz/UniFAR-FTUs huggingface dataset:
ASSOCIATION BETWEEN EPIRETINAL MEMBRANE, EPIRETINAL PROLIFERATION, AND PROGNOSIS OF FULL-THICKNESS MACULAR HOLE CLOSURE

Supplemental Digital Content is Available in the Text. Patients with the epiretinal membrane had a higher risk for adverse surgical outcomes for full-thickness macular hole and that epiretinal membrane location relative to the macular hole, and the presence of epiretinal proliferation may significantly affect surgical outcomes in full-thickness macular hole closure. Purpose: To demonstrate the effects of epiretinal membrane (ERM) and epiretinal proliferation on surgical outcomes for full-thickness macular hole. Methods: Nested case–control study with propensity score matching. Patients operated on for full-thickness macular hole between January 2011 and March 2020 were enrolled. The primary outcome was failure of the macular hole closure, and the secondary outcome was unfavorable hole closure (V or λ type closure) at 6 months after the surgery. Results: Five hundred and thirty-four eyes of 534 patients met the inclusion criteria. After 1:1 propensity score matching (127 pairs), patients demonstrating ERM were more likely to have a failure of hole closure (adjusted odds ratio, 2.71; 95% confidence interval, 1.19–6.14) and unfavorable hole closure (adjusted odds ratio, 2.07; 95% confidence interval, 1.16–3.71). Epiretinal membrane spanning the hole margin (hole marginal ERM) greatly increased the likelihood of unfavorable hole closure (adjusted odds ratio, 2.13; 95% confidence interval, 1.12–4.07). Patients with hole marginal-ERM + epiretinal proliferation were more likely to have a failure of hole closure (38.4%) compared with those with no ERM (11.8%). Conclusion: Patients with ERM had a higher risk for adverse surgical outcomes for full-thickness macular hole closure. The location of the ERM relative to the macular hole and the presence of epiretinal proliferation might affect the surgical outcomes for full-thickness macular hole closure.
A test of the photoprotection hypothesis for the evolution of autumn colours: Chlorophyll resorption, not anthocyanin production, is correlated with nitrogen translocation

A prominent hypothesis for the adaptive value of anthocyanin production in the autumn leaves of trees and shrubs is that anthocyanins protect leaves from photooxidative stress at low temperatures, allowing a better resorption of nutrients—in particular, nitrogen—before leaf fall. While there is evidence that anthocyanins enable photoprotection, it is not clear whether this translates to improved nitrogen translocation and how this can explain inter‐specific variation in autumn colours. A recent comparative analysis showed no correlation between temperature and anthocyanin production across species but did not analyse nitrogen content and nitrogen resorption efficiency. Here, we provide this comparison by analysing the nitrogen content of mature and senescent leaves and their autumn colours in 55 species of trees. We find no correlation between the presence of anthocyanins and the efficiency of nitrogen resorption. We find, instead, that nitrogen resorption is more efficient in species with yellow autumn colours, pointing to chlorophyll resorption, rather than anthocyanin synthesis, as the main determinant of nitrogen translocation efficiency. Hence, our results do not corroborate the photoprotection hypothesis for the evolution of autumn colours.
Subcutaneous Adipose Tissue Metabolic Function and Insulin Sensitivity in People With Obesity

We used stable isotope–labeled glucose and palmitate tracer infusions, a hyperinsulinemic-euglycemic clamp, positron emission tomography of muscles and adipose tissue after [18F]fluorodeoxyglucose and [15O]water injections, and subcutaneous adipose tissue (SAT) biopsy to test the hypotheses that 1) increased glucose uptake in SAT is responsible for high insulin-stimulated whole-body glucose uptake in people with obesity who are insulin sensitive and 2) putative SAT factors thought to cause insulin resistance are present in people with obesity who are insulin resistant but not in those who are insulin sensitive. We found that high insulin-stimulated whole-body glucose uptake in insulin-sensitive participants with obesity was not due to channeling of glucose into SAT but, rather, was due to high insulin-stimulated muscle glucose uptake. Furthermore, insulin-stimulated muscle glucose uptake was not different between insulin-sensitive obese and lean participants even though adipocytes were larger, SAT perfusion and oxygenation were lower, and markers of SAT inflammation, fatty acid appearance in plasma in relation to fat-free mass, and plasma fatty acid concentration were higher in the insulin-sensitive obese than in lean participants. In addition, we observed only marginal or no differences in adipocyte size, SAT perfusion and oxygenation, and markers of SAT inflammation between insulin-resistant and insulin-sensitive obese participants. Plasma fatty acid concentration was also not different between insulin-sensitive and insulin-resistant obese participants, even though SAT was resistant to the inhibitory effect of insulin on lipolysis in the insulin-resistant obese group. These data suggest that several putative SAT factors commonly implicated in causing insulin resistance are normal consequences of SAT expansion unrelated to insulin resistance.
Assessment of the Maximal Range of Motion from Initial Sensation of Stretching to the Limits of Tolerance.

The aim of this study was to determine whether the first sensation of stretching (ROMFSS) may predict the maximum range of motion (ROMMAX) in male (N = 37) and female (N = 32) volunteer subjects, and to assess the reliability of the ROM perceived by subjects in relation to a pre-determined ROM (ROM50%). Subjects attempted three experimental sessions with 48 hours between sessions 1 and 2 and 28 days between sessions 1 and 3. Within each session, five trials were performed with isokinetic equipment to assess posterior thigh muscle flexibility. The results revealed a strong and significant correlation between ROMMAX and ROMFSS for both sexes, females (r = 0.96, p < 0.001, R 2 = 0.92) and males (r = 0.91, p < 0.001; R 2 = 0.82). The accuracy of the model verified by the standard error of estimate (SEE) was high in the equations proposed for both female (SEE = 4.53%) and male (SEE = 5.45%). Our results revealed that ROMFSS may predict the ROMMAX for both male and female subjects. The ROMFSS may contribute to the development of evaluation methods that do not subject the individuals to conditions that may include unnecessary risk of injury and is well suited to monitor the training process of stretching exercises with submaximal loads.
Prognostic role of programmed cell death ligand-1 expression in head and neck cancer treated with programmed cell death protein-1/programmed cell death ligand-1 inhibitors: A meta-analysis based on clinical trials

Purpose: The purpose of our meta-analysis is to clarify whether the biomarker of programmed cell death ligand-1 (PD-L1) could predict the treatment efficacy and prognosis of programmed cell death protein-1 (PD-1)/PD-L1 immune-checkpoint inhibitors (ICIs) in head and neck cancer (HNC) patients. Materials and Methods: We performed the article search in four main online databases. The search deadline was September 8, 2020. To elucidate whether a positive or negative PD-L1 expression correlates with different efficacy and prognosis of PD-1/PD-L1–related therapy in HNC, the relative risk (RR) and 95% confidence interval (95% CI) were pooled. Our meta-analysis assigned the overall survival (OS) at 6 and 12 months and the objective response rate (ORR) for the primary end points. Results: The present meta-analysis included 11 relevant studies, which have 1663 HNC cases who received the treatment of PD-1/PD-L1 ICIs. The pooled results revealed that the high or positive expression of PD-L1 predicted better 6- and 12-month OS in head and neck squamous cell carcinoma (HNSCC) (RR 1.30, 95% CI: 1.02–1.65, P = 0.03; and RR 1.31, 95% CI: 1.05–1.62, P = 0.01). PD-L1 expressors were also relevant with higher ORR in HNC patients who had treatment of PD-1/PD-L1 inhibitors compared to PD-L1 nonexpressors (RR 1.84, 95% CI: 1.41–2.41, P < 0.00001). Conclusions: In summary, PD-L1–positive HNSCC patients portend favorable OS at 6 and 12 months from PD-1/PD-L1 ICIs. Increased ORR also favored to appear in PD-L1 expressors of HNC or recurrent/metastatic HNSCC who received PD-1/PD-L1 ICIs. Therefore, PD-L1 proved to be an appropriate biomarker to predict the clinical efficacy and prognosis of PD-1/PD-L1 ICIs in HNC.
Avaliação de efeitos de um extrato aquoso de cinnamomum zeylanicum L. na marcação de constituintes sanguíneos com tecnécio-99m e na morfologia das hemácias de ratos wistar

Radiobiocomplexos sao utilizados para obtencao de imagens em medicina nuclear e empregados na pesquisa basica. Constituintes sanguineos marcados com tecnecio-99m tem sido empregados como radiobiocomplexos e utilizados como modelo experimental para avaliacao de efeitos biologicos de drogas naturais ou sinteticas. A analise da forma e de parâmetros morfometricos (relacao perimetro/area) pode ser usada para avaliar os efeitos de drogas sobre a estrutura da membrana de hemacias. Cinnamomum zeylanicum (canela) e uma especiaria usada como planta medicinal para tratar doencas. O objetivo desse estudo foi avaliar efeitos de um extrato aquoso de Cinnamomum zeylanicum na marcacao de constituintes sanguineos com tecnecio-99m e na morfologia de hemacias de ratos Wistar. No tratamento in vitro, amostras de sangue de animais foram isoladas e incubadas com um extrato de canela. No tratamento in vivo, animais foram tratados com um extrato de canela e amostras de sangue foram isoladas. Em ambas as situacoes foram realizadas a radiomarcacao de constituintes sanguineos e a analise morfologica. Como controle, o sangue ou os animais foram tratados com cloreto de sodio 0,9%. Os dados obtidos nos experimentos de marcacao de constituintes sanguineos com tecnecio-99m indicaram que o tratamento in vitro com extrato de canela foi capaz de diminuir significativamente (p<0,05) a porcentagem de radioatividade nos compartimentos celulares e na fixacao das proteinas celulares e plasmaticas. Esses efeitos nao foram observados no tratamento in vivo. Os resultados obtidos na morfologia de hemacias sugerem que os tratamentos in vitro e in vivo nao alteram a forma nem a razao perimetro/area. O tratamento in vitro com o extrato aquoso de canela poderia afetar estruturas da membrana celular relacionadas ao transporte de Ions ou ao estado de oxidacao do ion estanoso ou do ion pertecnetato, alterando a marcacao de constituintes sanguineos com tecnecio-99m. Esse estudo e uma pesquisa experimental com carater multidisciplinar. Foi desenvolvido em colaboracao com diferentes Departamentos e Servicos da area biomedica do Hospital Universitario Pedro Ernesto, UERJ, atestando o carater multidisciplinar da pesquisa
HIV residual risk in Canada for apheresis source plasma donation without deferral for men who have sex with men

In Canada, men having sex with men (MSM) are deferred for 3 months from last sexual contact to reduce human immunodeficiency virus (HIV) risk to recipients. The aim of this paper was to model the Canadian residual risk of HIV‐positive source plasma incorporating pathogen inactivation (PI) under no MSM deferral scenarios for apheresis plasma donations.
Leptin system loss of function in the absence of obesity in zebrafish.

The leptin system plays a crucial role in the regulation of appetite and energy homeostasis in vertebrates. While the phenotype of morbid obesity due to leptin or leptin receptor (lepr) loss of function is well established in mammals, evidence in fish is controversial, questioning the role of leptin as the vertebrate adipostat. Here we report on 3 lepr loss of function (lof) and one leptin loss of function allele in zebrafish. In order to demonstrate that the lepr lof alleles cannot transduce a leptin signal, we measured socs3a transcription after intraperitoneal leptin which is abolished by lepr lof. None of the lepr/lepa lof alleles lead to obesity / a body growth phenotype. We explore possible reasons leading to the difference in published results and find that even slight changes in background genetics such as inbreeding siblings and cousins can lead to significant variance in growth.
Home blood pressure monitoring: methodology, clinical relevance and practical application: a 2021 position paper by the Working Group on Blood Pressure Monitoring and Cardiovascular Variability of the European Society of Hypertension

Supplemental Digital Content is available in the text The present paper provides an update of previous recommendations on Home Blood Pressure Monitoring from the European Society of Hypertension (ESH) Working Group on Blood Pressure Monitoring and Cardiovascular Variability sequentially published in years 2000, 2008 and 2010. This update has taken into account new evidence in this field, including a recent statement by the American Heart association, as well as technological developments, which have occurred over the past 20 years. The present document has been developed by the same ESH Working Group with inputs from an international team of experts, and has been endorsed by the ESH.
Cell contact guidance via sensing anisotropy of network mechanical resistance

Significance Cell contact guidance in aligned fibers is, in many ways, a final frontier in directed cell migration. Despite its ubiquitous importance in normal/pathological processes, notably metastasis from solid tumors, and scaffold design for tissue engineering/regenerative medicine, the signal that induces contact guidance in an aligned fiber network has defied elucidation. We report definitive demonstration of a biophysical signal sensed by fibroblasts cultured within aligned fibrils: mechanical resistance anisotropy, the resistance resulting from viscous and elastic properties of fibril network to pseudopod protrusion/retraction and how it differs in different directions (anisotropy). This discovery is of fundamental importance to understanding contact guidance, providing a rationale, currently lacking, for future studies of the intracellular signal transduction/response pathways for physiologically relevant contact guidance. Despite the ubiquitous importance of cell contact guidance, the signal-inducing contact guidance of mammalian cells in an aligned fibril network has defied elucidation. This is due to multiple interdependent signals that an aligned fibril network presents to cells, including, at least, anisotropy of adhesion, porosity, and mechanical resistance. By forming aligned fibrin gels with the same alignment strength, but cross-linked to different extents, the anisotropic mechanical resistance hypothesis of contact guidance was tested for human dermal fibroblasts. The cross-linking was shown to increase the mechanical resistance anisotropy, without detectable change in network microstructure and without change in cell adhesion to the cross-linked fibrin gel. This methodology thus isolated anisotropic mechanical resistance as a variable for fixed anisotropy of adhesion and porosity. The mechanical resistance anisotropy |Y*|−1 − |X*|−1 increased over fourfold in terms of the Fourier magnitudes of microbead displacement |X*| and |Y*| at the drive frequency with respect to alignment direction Y obtained by optical forces in active microrheology. Cells were found to exhibit stronger contact guidance in the cross-linked gels possessing greater mechanical resistance anisotropy: the cell anisotropy index based on the tensor of cell orientation, which has a range 0 to 1, increased by 18% with the fourfold increase in mechanical resistance anisotropy. We also show that modulation of adhesion via function-blocking antibodies can modulate the guidance response, suggesting a concomitant role of cell adhesion. These results indicate that fibroblasts can exhibit contact guidance in aligned fibril networks by sensing anisotropy of network mechanical resistance.
Impact of Anaerobic Antibacterial Spectrum on Cystic Fibrosis Airway Microbiome Diversity and Pulmonary Function

Supplemental Digital Content is available in the text. Background: The role of anaerobic organisms in the cystic fibrosis (CF) lung microbiome is unclear. Our objectives were to investigate the effect of broad (BS) versus narrow (NS) spectrum antianaerobic antibiotic activity on lung microbiome diversity and pulmonary function, hypothesizing that BS antibiotics would cause greater change in microbiome diversity without a significant improvement in lung function. Methods: Pulmonary function tests and respiratory samples were collected prospectively in persons with CF before and after treatment for pulmonary exacerbations. Treatment antibiotics were classified as BS or NS. Gene sequencing data from 16S rRNA were used for diversity analysis and bacterial genera classification. We compared the effects of BS versus NS on diversity indices, lung function and anaerobic/aerobic ratios. Statistical significance was determined by multilevel mixed-effects generalized linear models and mixed-effects regression models. Results: Twenty patients, 6–20 years of age, experienced 30 exacerbations. BS therapy had a greater effect on beta diversity than NS therapy when comparing time points before antibiotics to after and at recovery. After antibiotics, the NS therapy group had a greater return toward baseline forced expiratory volume at 1 second and forced expiratory flow 25%–75% values than the BS group. The ratio of anaerobic/aerobic organisms showed a predominance of anaerobes in the NS group with aerobes dominating in the BS group. Conclusions: BS antianaerobic therapy had a greater and possibly longer lasting effect on the lung microbiome of persons with CF, without achieving the recovery of pulmonary function seen with the NS therapy. Specific antibiotic therapies may affect disease progression by changing the airway microbiome.
Distinct mechanisms mediate X chromosome dosage compensation in Anopheles and Drosophila

CRISPR knockout of msl-2 and epigenome analyses in Anopheles reveal that X chromosome dosage compensation in mosquitos and Drosophila is achieved by two different molecular mechanisms. Sex chromosomes induce potentially deleterious gene expression imbalances that are frequently corrected by dosage compensation (DC). Three distinct molecular strategies to achieve DC have been previously described in nematodes, fruit flies, and mammals. Is this a consequence of distinct genomes, functional or ecological constraints, or random initial commitment to an evolutionary trajectory? Here, we study DC in the malaria mosquito Anopheles gambiae. The Anopheles and Drosophila X chromosomes evolved independently but share a high degree of homology. We find that Anopheles achieves DC by a mechanism distinct from the Drosophila MSL complex–histone H4 lysine 16 acetylation pathway. CRISPR knockout of Anopheles msl-2 leads to embryonic lethality in both sexes. Transcriptome analyses indicate that this phenotype is not a consequence of defective X chromosome DC. By immunofluorescence and ChIP, H4K16ac does not preferentially enrich on the male X. Instead, the mosquito MSL pathway regulates conserved developmental genes. We conclude that a novel mechanism confers X chromosome up-regulation in Anopheles. Our findings highlight the pluralism of gene-dosage buffering mechanisms even under similar genomic and functional constraints.
The miR-182-5p/FGF21/acetylcholine axis mediates the crosstalk between adipocytes and macrophages to promote beige fat thermogenesis

A dynamically regulated microenvironment, which is mediated by crosstalk between adipocytes and neighboring cells, is critical for adipose tissue homeostasis and function. However, information on key molecules and/or signaling pathways regulating the crosstalk remains limited. In this study, we identify adipocyte miRNA-182-5p (miR-182-5p) as a crucial antiobesity molecule that stimulated beige fat thermogenesis by promoting the crosstalk between adipocytes and macrophages. miR-182-5p was highly enriched in thermogenic adipocytes, and its expression was markedly stimulated by cold exposure in mice. In contrast, miR-182-5p expression was significantly reduced in adipose tissues of obese humans and mice. Knockout of miR-185-5p decreased cold-induced beige fat thermogenesis whereas overexpression of miR-185-5p increased beiging and thermogenesis in mice. Mechanistically, miR-182-5p promoted FGF21 expression and secretion in adipocytes by suppressing nuclear receptor subfamily 1 group D member 1 (Nr1d1) at 5′-UTR, which in turn stimulates acetylcholine synthesis and release in macrophages. Increased acetylcholine expression activated the nicotine acetylcholine receptor in adipocytes, which stimulated PKA signaling and consequent thermogenic gene expression. Our study reveals a key role of the miR-182-5p/FGF21/acetylcholine/acetylcholine receptor axis that mediates the crosstalk between adipocytes and macrophages to promote beige fat thermogenesis. Activation of the miR-182-5p–induced signaling pathway in adipose tissue may be an effective approach to ameliorate obesity and associated metabolic diseases.
The Molecular Signature of High-intensity Training in the Human Body

Abstract High-intensity training is becoming increasingly popular outside of elite sport for health prevention and rehabilitation. This expanded application of high-intensity training in different populations requires a deeper understanding of its molecular signature in the human body. Therefore, in this integrative review, cellular and systemic molecular responses to high-intensity training are described for skeletal muscle, cardiovascular system, and the immune system as major effectors and targets of health and performance. Different kinds of stimuli and resulting homeostatic perturbations (i. e., metabolic, mechanical, neuronal, and hormonal) are reflected, taking into account their role in the local and systemic deflection of molecular sensors and mediators, and their role in tissue and organ adaptations. In skeletal muscle, a high metabolic perturbation induced by high-intensity training is the major stimulus for skeletal muscle adaptation. In the cardio-vascular system, high-intensity training induces haemodynamic stress and deflection of the Ca 2+ handling as major stimuli for functional and structural adaptation of the heart and vessels. For the immune system haemodynamic stress, hormones, exosomes, and O2 availability are proposed stimuli that mediate their effects by alteration of different signalling processes leading to local and systemic (anti)inflammatory responses. Overall, high-intensity training shows specific molecular signatures that demonstrate its high potential to improve health and physical performance.
A phase 1/2 study of the combination of acalabrutinib and vistusertib in patients with relapsed/refractory B-cell malignancies

Abstract In a phase 1b study of acalabrutinib (a covalent Bruton tyrosine kinase (BTK) inhibitor) in combination with vistusertib (a dual mTORC1/2 inhibitor) in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), multiple ascending doses of the combination as intermittent or continuous schedules of vistusertib were evaluated. The overall response rate was 12% (3/25). The pharmacodynamic (PD) profile for acalabrutinib showed that BTK occupancy in all patients was >95%. In contrast, PD analysis for vistusertib showed variable inhibition of phosphorylated 4EBP1 (p4EBP1) without modulation of AKT phosphorylation (pAKT). The pharmacokinetic (PK)/PD relationship of vistusertib was direct for TORC1 inhibition (p4EBP1) but did not correlate with TORC2 inhibition (pAKT). Cell-of-origin subtyping or next-generation sequencing did not identify a subset of DLBCL patients with clinical benefit; however, circulating tumor DNA dynamics correlated with radiographic response. These data suggest that vistusertib does not modulate targets sufficiently to add to the clinical activity of acalabrutinib monotherapy. Clinicaltrials.gov identifier: NCT03205046.