Miracle-dz/UniFAR-FTUs huggingface dataset:
Platelet factor 4 limits neutrophil extracellular trap– and cell-free DNA–induced thrombogenicity and endothelial injury

Plasma cell-free DNA (cfDNA), a marker of disease severity in sepsis, is a recognized driver of thromboinflammation and a potential therapeutic target. In sepsis, plasma cfDNA is mostly derived from neutrophil extracellular trap (NET) degradation. Proposed NET-directed therapeutic strategies include preventing NET formation or accelerating NET degradation. However, NET digestion liberates pathogens and releases cfDNA that promote thrombosis and endothelial cell injury. We propose an alternative strategy of cfDNA and NET stabilization with chemokine platelet factor 4 (PF4, CXCL4). We previously showed that human PF4 (hPF4) enhances NET-mediated microbial entrapment. We now show that hPF4 interferes with thrombogenicity of cfDNA and NETs by preventing their cleavage to short-fragment and single-stranded cfDNA that more effectively activates the contact pathway of coagulation. In vitro, hPF4 also inhibits cfDNA-induced endothelial tissue factor surface expression and von Willebrand factor release. In vivo, hPF4 expression reduced plasma thrombin-antithrombin (TAT) levels in animals infused with exogenous cfDNA. Following lipopolysaccharide challenge, Cxcl4–/– mice had significant elevation in plasma TAT, cfDNA, and cystatin C levels, effects prevented by hPF4 infusion. These results show that hPF4 interacts with cfDNA and NETs to limit thrombosis and endothelial injury, an observation of potential clinical benefit in the treatment of sepsis.
17β‐Estradiol mediates TGFBR3/Smad2/3 signaling to attenuate the fibrosis of TGF‐β1‐induced bovine endometrial epithelial cells via GPER

Abnormal function and fibrosis of endometrium caused by cows' endometritis pose difficult implantation of embryos and uterine cavity adhesions. 17β‐Estradiol (E2) serves as the most effective aromatized estrogen, and its synthetase and receptors have been detected in the endometrium. Studies have demonstrated the positive role of estrogen in combating pathological fibrosis in diverse diseases. However, it is still unknown whether E2 regulates endometrium fibrosis in bovine endometritis. Herein, we evaluated the expression patterns of transforming growth factor‐β1 (TGF‐β1), epithelial‐mesenchymal transformation (EMT)‐related proteins (α‐SMA, vimentin N‐cadherin and E‐cadherin), cytochrome P450 19A1 (CYP19A1), and G protein‐coupled estrogen receptor (GPER) in bovine healthy endometrium and Inflammatory endometrium. Our data showed that the inflamed endometrium presented low CYP19A1 and GPER expression, and significantly higher EMT process versus the normal tissue. Moreover, we established a TGF‐β1‐induced fibrosis model in BEND cells, and found that E2 inhibited the EMT process of BEND cells in a dose‐dependent manner. The anti‐fibrotic effect of E2 was blocked by the GPER inhibitor G15, but not the estrogen nuclear receptors (ERs) inhibitor ICI182780. Moreover, the GPER agonist G1 inhibited fibrosis and Smad2/3 phosphorylation but increased the expression of TGFBR3 in BEND cells. Transfection with TGFBR3 small interfering RNA blocked the effect of G1 on fibrosis of BEND cells and upregulated the expression of P‐Smad2/3. Our in vivo data also showed that E2 and G1 affected uterus fibrosis in mice endometritis model caused by LPS, which was associated with the inhibition of TGFBR3/Smad2/3 signaling. In conclusion, our data implied that E2 alleviates the fibrosis of TGF‐β1‐induced BEND cells, which is associated with the GPER mediation of TGFBR3/Smad2/3 signaling.
Real-world clinical management of individuals with Rett syndrome: a physician survey

Abstract Background Rett syndrome (RTT) is a severe neurodevelopmental disorder. Management strategies are heterogeneous with no clear definition of success. This study describes physician decision-making regarding diagnosis, therapeutic goals, and management strategies to better understand RTT clinical management in the US. Methods This study was conducted among practicing physicians, specifically neurologists and pediatricians in the US with experience treating ≥2 individuals with RTT, including ≥1 individuals within the past two years. In-depth interviews with five physicians informed survey development. A cross-sectional survey was then conducted among 100 physicians. Results Neurologists had treated more individuals with RTT (median: 12 vs. 5, p < 0.001) than pediatricians throughout their career and were more likely to report being “very comfortable” managing RTT (31 vs. 4%, p < 0.001). Among physicians with experience diagnosing RTT (93%), most evaluated symptoms (91%) or used genetic testing (86%) for RTT diagnoses; neurologists used the 2010 consensus diagnostic criteria more than pediatricians (54 vs. 29%; p = 0.012). Improving the quality of life (QOL) of individuals with RTT was the most important therapeutic goal among physicians, followed by improving caregivers’ QOL. Most physicians used clinical practice guidelines to monitor the progress of individuals with RTT, although neurologists relied more on clinical scales than pediatricians. Among all physicians, the most commonly treated symptoms included behavioral issues, epilepsy/seizures, and feeding issues. Management strategies varied by symptom, with referral to appropriate specialists being common across symptoms. A large proportion of physicians (37%) identified the lack of novel therapies and reliance on symptom-specific management as an unmet need. Conclusion Although most physicians had experience and were comfortable diagnosing and treating individuals with RTT, better education and support among pediatricians is warranted. Additionally, novel treatments that target multiple symptoms associated with RTT could reduce the burden and improve the QOL of individuals with RTT and their caregivers.
The characterization of CD8+ T-cell responses in COVID-19

ABSTRACT This review gives an overview of the protective role of CD8+ T cells in SARS-CoV-2 infection. The cross-reactive responses intermediated by CD8+ T cells in unexposed cohorts are described. Additionally, the relevance of resident CD8+ T cells in the upper and lower airway during infection and CD8+ T-cell responses following vaccination are discussed, including recent worrisome breakthrough infections and variants of concerns (VOCs). Lastly, we explain the correlation between CD8+ T cells and COVID-19 severity. This review aids in a deeper comprehension of the association between CD8+ T cells and SARS-CoV-2 and broadens a vision for future exploration.
EFFECT OF RAINFALL INTENSITY, SLOPE, LAND USE AND ANTECEDENT SOIL MOISTURE ON SOIL EROSION IN AN ARID ENVIRONMENT

Most climate change scenarios predict a significant increase in the frequency of high intensity rainfall events especially in the dry areas, which will increase runoff and soil erosion. Understanding the factors that control soil erosion is crucial to recommending appropriate measures to protect soils and reduce their vulnerability. The objective of this research was to investigate the effect of rainfall intensity, slope, land use and antecedent soil moisture on soil erosion and runoff. Twelve sites from Al‐Muwaqqar watershed, Jordan, were selected to represent six slope angles: 1, 2, 3, 5, 7 and 9%. Two sites, one cultivated with barley and one as rangeland, were selected within each slope. Erosion was measured under three rainfall intensities: 3, 5 and 10 mm h−1; and three different antecedent soil moisture contents: dry, wet and very wet; using a rotating disk rainfall simulator. Regression equations indicated that rainfall intensity was the most important factor affecting soil erosion and that erosion could occur at a relatively small intensity on wet soils as a result of subsequent rainfall events. Soil erosion on cultivated land was primarily affected by moisture content, while on uncultivated land, it was mostly affected by slope steepness. Rainfall intensity, slope and antecedent moisture explained 84–89 and 59–66% of the variation in runoff and soil loss, respectively. The results indicated the significant influence of cultivating the land on soil erosion. Copyright © 2013 John Wiley & Sons, Ltd.
Improving physician wellness through the Applied Mindfulness Program for Medical Personnel: findings from a prospective qualitative study

Background: Physicians play a critical role across health care delivery systems, yet their own well-being is often overlooked; mindfulness has been widely recommended as a promising modality to support physician wellness. We sought to explore how physicians experience and engage with a 5-week applied mindfulness program and how they perceive its impact on their personal well-being in the context of their daily lives. Method: We delivered the Applied Mindfulness Program for Medical Personnel (AMP-MP) at a tertiary care hospital in downtown Toronto, Canada. This prospective qualitative study consists of a thematic analysis of post-program interviews with physicians, from across different specialties, who participated in the AMP-MP. The program includes 2-hour sessions, delivered once a week over 5 weeks, and is based on the teachings of Thích Nhất Hạnh. Results: We interviewed 28 physicians after they completed the AMP-MP. Our data show that a 5-week training was sufficient for physicians to develop a foundational level of mindfulness that integrated into their daily life. Two themes were identified: mindfulness encourages behavioural and cognitive changes that facilitate well-being, and mindfulness improves communication with patients and colleagues. Interpretation: Our results show applied mindfulness to be well received by physicians as an effective modality to increase their perceived sense of wellness and enhance communication with their patients and colleagues. Further research is necessary to better understand the individual and systemic implications of mindfulness training, and how this modality can complement other efforts being made to address and maintain physician wellness.
SxBLxM Melezi Kuzularda Besi ve Karkas Özellikleri Aras›ndaki Fenotipik Korelasyonlar

Ozet: Bu araflt›rma, 35-5 gunde sutten kesilen SxBLxM melezi 40 bafl kuzuda besi ve karkas ozellikleri aras›ndaki iliflkileri belirlemek icin yap›lm›flt›r. Araflt›rmada besi bafl› canl› a¤›rl›¤› ile gunluk youn yem tuketimi ve gunluk canl› a¤›rl›k kazanc› aras›nda onemli iliflkiler saptanm›flt›r(P<0.05). Besi ozelliklerinden besi sonu canl› a¤›rl›¤› ile sar› genifllii, vucut uzunluu ve go¤us genifllii aras›nda pozitif iliflkiler belirlenmifltir. Kesim ozelliklerinden s›cak ve souk karkas a¤›rl›¤›n›n, uc pirzola ozelliklerinden et(g) ve ya¤(g) ile olan iliflkisi de onemli bulunmufltur(P<0.01). Bobrek ya¤› a¤›rl›¤›n›n sadece ya¤(%) ile olan iliflkisi onemlidir(P<0.01). Kemik a¤›rl›¤›(g) ile dier kesim ozellikleri aras›ndaki iliflkiler onemsiz bulunmufltur. Abstract: This research was carried out to determine the relationships between the fattening and carcass characteristics of 40 weaned 35-5 day-old SxBLxM crossbred lambs. Significant relationships between initial body weight of fattening, daily intake and daily gain were found. Positive relationships were found between body weight and rump width, and body length and chest width. Moreover, there was a significant relationship between the hot and cold carcass weight and the meat and fat. In addition, a of the carcass. No significant relationship was found between the bone and the other characteristics.
Thalamic connectivity topography in newborns with spina bifida: association with neurological functional level but not developmental outcome at 2 years

Abstract Spina bifida affects spinal cord and cerebral development, leading to motor and cognitive delay. We investigated whether there are associations between thalamocortical connectivity topography, neurological function, and developmental outcomes in open spina bifida. Diffusion tensor MRI was used to assess thalamocortical connectivity in 44 newborns with open spina bifida who underwent prenatal surgical repair. We quantified the volume of clusters formed based on the strongest probabilistic connectivity to the frontal, parietal, and temporal cortex. Developmental outcomes were assessed using the Bayley III Scales, while the functional level of the lesion was assessed by neurological examination at 2 years of age. Higher functional level was associated with smaller thalamo-parietal, while lower functional level was associated with smaller thalamo-temporal connectivity clusters (Bonferroni-corrected P < 0.05). Lower functional levels were associated with weaker thalamic temporal connectivity, particularly in the ventrolateral and ventral anterior nuclei. No associations were found between thalamocortical connectivity and developmental outcomes. Our findings suggest that altered thalamocortical circuitry development in open spina bifida may contribute to impaired lower extremity function, impacting motor function and independent ambulation. We hypothesize that the neurologic function might not merely be caused by the spinal cord lesion, but further impacted by the disruption of cerebral neuronal circuitry.
Baseline haemoglobin variability by measurement technique in pregnant people on the day of childbirth

Point‐of‐care haemoglobin measurement devices may play an important role in the antenatal detection of anaemia in pregnant people and may be useful in guiding blood transfusion during resuscitation in obstetric haemorrhage. We compared baseline haemoglobin variability of venous and capillary HemoCue® haemoglobin, and Masimo® Rad‐67 Pulse CO‐Oximeter haemoglobin with laboratory haemoglobin in people on the day of their planned vaginal birth. A total of 180 people undergoing planned vaginal birth were enrolled in this prospective observational study. Laboratory haemoglobin was compared with HemoCue and Masimo Rad‐67 Pulse CO‐Oximeter measurements using Bland–Altman analysis, calculating mean difference (bias) and limits of agreement. Five (2.8%) people had anaemia (haemoglobin < 110 g.l‐1). Laboratory haemoglobin and HemoCue venous haemoglobin comparison showed an acceptable bias (SD) 0.7 (7.54) g.l‐1 (95%CI ‐0.43–1.79), with limits of agreement ‐14.10–15.46 g.l‐1 and acceptable agreement range of 29.6 g.l‐1. Laboratory and HemoCue capillary haemoglobin comparison showed an unacceptable bias (SD) 13.3 (14.12) g.l‐1 (95%CI 11.17–15.34), with limits of agreement ‐ 14.42–40.93 g.l‐1 and unacceptable agreement range of 55.3 g.l‐1. Laboratory and Masimo haemoglobin comparison showed an unacceptable bias (SD) ‐14.0 (11.15) g.l‐1 (95%CI ‐15.63 to ‐12.34), with limits of agreement to ‐35.85 to 7.87 g.l‐1 and acceptable agreement range of 43.7 g.l−1. Venous HemoCue, with its acceptable bias and limits of agreement, should be applied more widely in the antenatal setting to detect, manage and risk stratify pregnant people with anaemia. HemoCue capillary measurement under‐estimated haemoglobin and Masimo haemoglobin measurement over‐estimated, limiting their clinical use. Serial studies are needed to determine if the accuracy of venous HemoCue haemoglobin measurement is sustained in other obstetric settings.
OLD RED SEQUENCE, SOUTHWEST NORWAY

LIE, L. G. , STORETVEDT, K. M. , GJELLESTAD, GURo: The palaeomag­ netism of the Kvarnshesten Old Red sequence, southwest Norway. Norsk Geologisk Tidsskrift, Vol. 49, pp. 241-249. Oslo 1969. The inferred pole position (22"N, 170°E) for the Kvarnshesten Old Red sequence is in fairly good harmony with other Old Red data of southern Norway. However, a deviation in declination of about 15° is thought to have arisen from a rotation (anti-clockwise) of this complex, a conclusion which is compatible with the geological observations. The stable remanence is considered as a mtemperature viscous magnetization acquired during the time of diagenesis.
Correlation between baseline immature platelets fraction levels and peak troponin in patients with acute myocardial infarction

Introduction Elevated peak cardiac troponin levels have been linked with increased morbidity and mortality in patients with acute myocardial infarction (AMI). Immature Platelets are young and relatively large platelets that are hyper-reactive and pro-thrombotic compared to regular platelets. Increased immature platelet fraction (IPF) has been associated with an elevated risk of thrombotic events. We hypothesize that patients with higher IPF levels during AMI, will experience a more severe infarct, leading to elevated peak troponin levels. Methods Clinical data from patients admitted to the cardiology division between 2018 and 2022, who were diagnosed with AMI and underwent an IPF testing. Univariate and multivariate regression analyses were performed to identify predictors of elevated peak troponin. Results Among the 277 patients diagnosed with AMI who underwent IPF testing, 113 had (STEMI) and 164 had (NSTEMI). The median value of IPF of 4.2% was used as the threshold for defining elevated IPF. Notably, among STEMI patients, those with IPF ≥ 4.2% had significantly higher peak troponin levels (P = 0.021). Conversely, no significant difference in peak troponin levels was observed among NSTEMI patients (P = 0.348). Multivariate analysis identified patients with STEMI in the higher IPF group as one of the significant predictors for elevated peak troponin levels. Conclusion This study revealed a correlation between higher baseline IPF levels and increased peak troponin levels specifically in STEMI patients, while no such association was found in NSTEMI patients. Incorporating IPF levels above the median into risk stratification scores for STEMI patients may provide valuable support for adopting a more proactive therapeutic approach.
Racial and Ethnic Disparity in Preoperative Chemosensitivity and Survival in Patients With Early-Stage Breast Cancer

Key Points Question Is there racial and ethnic disparity in preoperative chemosensitivity in early-stage breast cancer? Findings In this cohort study of 103 605 patients with early-stage breast cancer who received neoadjuvant chemotherapy, Black patients had more refractory disease in ERBB2-positive and triple-negative breast cancer. Black patients had significantly inferior survival rates compared with other races and ethnicities across all breast cancer subtypes, and this disparity was pronounced among those with sensitive and refractory preoperative chemosensitivity. Meaning These findings suggest the presence of racial and ethnic disparity in preoperative chemosensitivity among patients with early-stage breast cancer and that there is a need for personalized treatment options for Black patients.
Coiled-coil-mediated dimerization of Atg16 is required for binding to the PROPPIN Atg21

PROPPINs/WIPIs are β-propeller proteins that bind phosphoinositides and contribute to the recruitment of protein complexes involved in membrane remodelling processes such as autophagosome formation and endosomal trafficking. Yeast Atg21 and mammalian WIPI2 interact with Atg16/ATG16L1 to mediate recruitment of the lipidation machinery to the autophagosomal membrane. Here, we used the reverse double two-hybrid method (RD2H) to identify residues in Atg21 and Atg16 critical for protein–protein binding. Although our results are generally consistent with the crystal structure of the Atg21-Atg16 complex reported previously, they also reveal that dimerization of the Atg16 coiled-coil domain is required for Atg21 binding. Furthermore, most of the residues identified in Atg21 are conserved in WIPI2 and we showed that these residues also mediate ATG16L1 binding. Strikingly, these residues occupy the same position in the β-propeller structure as residues in PROPPINs/WIPIs Hsv2 and WIPI4 that mediate Atg2/ATG2A binding, supporting the idea that these proteins use different amino acids at the same position to interact with different autophagic proteins. Finally, our findings demonstrate the effectiveness of the RD2H system to identify critical residues for protein–protein interactions and the utility of this method to generate combinatory mutants with a complete loss of binding capacity.
Cross-cultural evaluation of learning and memory using a consonant-vowel-consonant trigram list

Abstract Objective: Word list-learning tasks are commonly used to evaluate auditory-verbal learning and memory. However, different frequencies of word usage, subtle meaning nuances, unique word phonology, and different preexisting associations among words make translation across languages difficult. We administered lists of consonant-vowel-consonant (CVC) nonword trigrams to independent American and Italian young adult samples. We evaluated whether an auditory list-learning task using CVC nonword trigrams instead of words could be applied cross-culturally to evaluate similar learning and associative memory processes. Participants and Methods: Seventy-five native English-speaking (USA) and 104 native Italian-speaking (Italy) university students were administered 15-item lists of CVC trigrams using the Rey Auditory Verbal Learning Test paradigm with five study-test trials, an interference trial, and short- and long-term delayed recall. Bayesian t tests and mixed-design ANOVAs contrasted the primary learning indexes across the two samples and biological sex. Results: Performance was comparable between nationalities on all primary memory indices except the interference trial (List B), where the Italian group recalled approximately one item more than the American sample. For both nationalities, recall increased across the five learning trials and declined significantly on the postinterference trial, demonstrating susceptibility to retroactive interference. No effects of sex, age, vocabulary, or depressive symptoms were observed. Conclusions: Using lists of unfamiliar nonword CVC trigrams, Italian and American younger adults showed a similar performance pattern across immediate and delayed recall trials. Whereas word list-learning performance is typically affected by cultural, demographic, mood, and cognitive factors, this trigram list-learning task does not show such effects, demonstrating its utility for cross-cultural memory assessment.
Calibrating a land surface model of varying complexity using multicriteria methods and the Cabauw dataset

Abstract The multicriteria methodology, which provides a means to estimate optimal ranges for land surface model parameter values via calibration, is evaluated. Following calibration, differences between schemes resulting from effective parameter values can be isolated from differences resulting from scheme structure or scheme parameterizations. The method is applied to the Project for the Intercomparison of Land Surface Parameterization Schemes (PILPS) phase-2a data from the Cabauw site in the Netherlands using the Chameleon Surface Model (CHASM) as the surrogate for a range of land surface schemes. Simulations are performed calibrating six modes of CHASM, representing a range of land surface complexity, against observed net radiation and latent and sensible heat fluxes. The six modes range from a simple bucket model to a complex mosaic-type structure with separate energy balances for each mosaic tile and explicit treatment of transpiration, canopy interception, and bare-ground evaporation. Results demon.