Miracle-dz/UniFAR-FTUs huggingface dataset:
Complement Activation Impaired in Its Ability To Regulate Lupus Susceptibility Interval Is Not Sle1c An Allelic Variant of Crry in the Murine

The Sle1c subinterval on distal murine chromosome 1 confers loss of tolerance to chromatin. Cr2 , which encodes complement receptors 1 and 2 (CR1/CR2; CD35/CD21), is a strong candidate gene for lupus susceptibility within this interval based on structural and functional alterations in its protein products. CR1-related protein/gene Y ( Crry ) lies 10 kb from Cr2 and encodes a ubiquitously expressed complement regulatory protein that could also play a role in the pathogenesis of systemic lupus erythematosus. Crry derived from B6. Sle1c congenic mice migrated at a higher m.w. by SDS-PAGE compared with B6 Crry, as a result of differential glycosylation. A single-nucleotide polymorphism in the ﬁrst short consensus repeat of Sle1c Crry introduced a novel N-linked glycosylation site likely responsible for this structural alteration. Five additional single-nucleotide polymorphisms in the signal peptide and short consensus repeat 1 of Sle1c Crry were identiﬁed. However, the cellular expression of B6 and B6. Sle1c Crry and their ability to regulate the classical pathway of complement were not signiﬁcantly different. Although soluble Sle1c Crry regulated the alternative pathway of complement more efﬁciently than B6 Crry, as a membrane protein, it regulated the alternative pathway equivalently to B6 Crry. These data fail to provide evidence for a functional effect of the structural alterations in Sle1c Crry and suggest that the role of Cr2 in the Sle1c autoimmune phenotypes can be isolated in recombinant congenic mice containing both genes. The Journal of Immunology , 2010, 185: 2331–2339.
Adjustable on-chip sub-capacitor design

The present invention capacitor having a capacitance value that is accurately calibrated within the range of between about 1% and 5% of the target value is mounted on it, to provide a silicon semiconductor chip. A one or more on-chip VNCAP or MIMCAP capacitor, to improve the uniform electrostatic capacitance value of the capacitor, using a variable MOS capacitor. Thus, a capacitor having a capacitance value that is adjusted precisely to the range of between about 1% and 5% of its design value is mounted thereon, it is possible to manufacture a silicon semiconductor chip. This optimization, for DC decoupling, by the use of back-to-back connection between a pair of variable MOS capacitor can be achieved. It is by inserting a pair of back-to-back variable MOS capacitor in FEOL, with the parallelism of the on-chip BEOL capacitance of VNCAP and / or MIMCAP capacitor. FIELD 4
Multi‐scale attention network for segmentation of electron dense deposits in glomerular microscopic images

Electron dense deposit on the epithelial side of the glomerular capillary basement membrane is one of the pathological changes of membranous nephropathy. Automatic segmentation of deposits can relieve clinicians from the tedious and manual effort of identifying and localizing region of interest (ROI) in medical images and also assist to diagnose membranous nephropathy. Electron dense deposits are characterized by different sizes, irregular shapes, and low contrast to surrounding tissue structures in glomerular electron microscopy images. Considering the characteristics of dense deposits, we propose a multi‐scale attention network for automatic segmentation of electron dense deposits of glomeruli in electron microscope images. Our method is built on the fully convolutional network but also takes advantages of the multi‐scale skip connections and attention mechanism. Specifically, the multi‐scale skip connection combines feature maps of different scales, makes the segmentation field larger, and integrates the shallow features of the image and high‐level semantic information, which is more conducive to distinguishing dense deposits. At the same time, attention mechanism can focus on salient structures that normally produces a distinguishable feature representation. To evaluate the segmentation performance of the proposed method, we also collected a dataset of electron microscope images of membranous nephropathy. To the best of our knowledge, this is the largest image dataset for segmentation of glomerular basement membrane dense deposits. Experimental result shows that our model can accurately segment ordinary‐sized dense deposits. Compared with state‐of‐the‐art methods, our proposed method lower both false positive and false negative segmentation of small‐sized protein sediments.
Parent Artery Complex Coil Protection for Side-Branched Wide-Neck Aneurysms

This study aimed to validate the usefulness of parent artery complex coil protection for the treatment of wide-neck, side-branched, and ruptured aneurysms. A microcatheter was first introduced into the aneurysmal sac, and another microcatheter was introduced into the parent artery or near the orifice of the branch artery. A framing coil was deployed partially from the first microcatheter, and a protection coil was deployed from the second microcatheter to prevent protrusion of the first framing coil to the parent artery and side branches. After the first framing coil insertion, the protection coil was withdrawn to confirm the stability of the framing coil and blood flow. The procedures with this technique were successful for 3 patients. Parent artery complex coil protection can be an effective and safe coil embolization technique for the preservation of parent and side branch arteries and an alternative method for emergent ruptured cases.
COPD_A_276792 3183..3192

1Birmingham Acute Care Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK; 2NIHR Clinical Research Facility Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK Abstract: Alpha-1 antitrypsin deficiency (AATD) is a genetic condition characterised by low circulating levels of alpha-1 antitrypsin (AAT), a serine proteinase inhibitor. The most common deficiency variants are the S and Z mutations, which cause the accumulation of misfolded AAT in hepatocytes resulting in endoplasmic reticular stress and insufficient release of AAT into the circulation (<11μmol/L). This leads to liver disease, as well as an increased risk of emphysema due to unopposed proteolytic activity of neutrophil-derived serine proteinases in the lungs. AATD has been traditionally viewed as an inflammatory disorder caused directly by a proteinase-antiproteinase imbalance in the lung, but increasing evidence suggests that low AAT levels may affect other cellular functions. Recently, AAT polymers have been identified in both monocytes and macrophages from AATD patients and evidence is building that these cells may also play a role in the development of AATD lung disease. Alveolar macrophages are phagocytic cells that are important in the lung immune response but are also implicated in driving inflammation. This review explores the potential implications of monocyte and macrophage involvement in non-liver AAT synthesis and the pathophysiology of AATD lung disease.
Effects of Muscles on Bone Metabolism—with a Focus on Myokines

Skeletal muscles and bones, the largest tissues in the body of a non-obese person, comprise the musculoskeletal system, which allows mobility and protects internal organs. Although muscles and bones are closely related throughout life, observations during development and aging and in human and animal disuse models have revealed the synchronization of tissue mass such that muscle phenotype changes precede alterations in bone mineral density and strength. This review discussed that mechanical forces, which have been the traditional research focus, are not the only mechanism by which muscle-derived signals may affect bone metabolism and emphasized the significance of skeletal muscles as an endocrine organ that secretes bone-regulatory factors. Consequently, both mechanical and biochemical aspects should be considered to fully understand muscle–bone crosstalk. This review also suggested that specific myokines could be ideal therapeutic targets for osteoporosis to both increase bone formation and reduce bone resorption; moreover, these myokines could also be potential circulating biomarkers to predict musculoskeletal health.
Prewarming for Prevention of Hypothermia in Older Patients Undergoing Hand Surgery Under Brachial Plexus Block

Background Older patients are more vulnerable to inadvertent perioperative hypothermia. Prewarming contributes to the prevention of inadvertent perioperative hypothermia in patients under general or neuraxial anesthesia. However, the effects of brachial plexus block (BPB) on thermoregulation and the efficacy of prewarming in the prevention of hypothermia in older patients undergoing surgery with BPB remain unclear. This study evaluated the effects of BPB on thermoregulation and the efficacy of prewarming during BPB in older patients. Methods Patients aged ≥65 years were randomly allocated to receive either standard preoperative insulation (control group, n=20) or preanesthetic forced-air warming for 20 minutes before BPB (prewarming group, n=20). During the perioperative period, tympanic temperatures were measured. Thermal comfort scores and shivering grades were also obtained. Results The tympanic temperatures at the end of surgery did not differ between the groups (36.9°C±0.5°C and 37.0°C±0.4°C in the control and prewarming groups, respectively; p=0.252). The maximum temperature change was significantly lower in the prewarming group compared to the control group (0.36°C±0.4°C and 0.65°C±0.3°C, respectively; p=0.013). The hypothermia incidence and severity, thermal comfort scores, and shivering grades did not differ between the groups. Conclusion Regardless of the application of prewarming, BPB did not cause a clinically significant impairment of thermoregulation. Moreover, the efficacy of prewarming appeared to be low; thus, it may not be routinely required in patients undergoing orthopedic hand surgery under BPB.
Microscopic anatomy of the upper aerodigestive tract in harbor seals (Phoca vitulina): Functional adaptations to swallowing

Abandoned harbor seal pups (Phoca vitulina) are frequently recovered by rehabilitation centers and often require intensive nursing, gavage feeding and swallowing rehabilitation prior to anticipated release. Seal upper aerodigestive tract (UAT) histology descriptions relevant to deglutition are limited, impacting advances in rehabilitation practice. Therefore, we examined the histological characteristics of the harbor seal UAT to understand species‐specific functional anatomy and characterize adaptations. To this end, we conducted gross dissections, compiled measurements and reviewed histologic features of the UAT structures of 14 preweaned harbor seal pups that died due to natural causes or were humanely euthanized. Representative samples for histologic evaluation included the tongue, salivary glands, epiglottis, and varying levels of the trachea and esophagus. Histologically, there was a prominent muscularis in the tongue with fewer lingual papillae types compared to humans. Abundant submucosal glands were observed in lateral and pharyngeal parts of the tongue and rostral parts of the esophagus. When compared to other mammalian species, there was a disproportionate increase in the amount of striated muscle throughout the length of the esophageal muscularis externa. This may indicate a lesser degree of autonomic control over the esophageal phase of swallowing in harbor seals. Our study represents the first detailed UAT histological descriptions for neonatal harbor seals. Collectively, these findings support specific anatomic and biomechanical adaptations relevant to suckling, prehension, and deglutition. This work will inform rehabilitation practices and guide future studies on swallowing physiology in harbor seals with potential applications to other pinniped and otariid species in rehabilitation settings.
Antimicrobial Use in Pediatric Oncology and Hematology: Protocol for a Multicenter Point-Prevalence Study With Qualitative Expert Panel Assessment

Background Because infections are a major driver of morbidity and mortality in children with hematologic or oncologic diseases, antimicrobials are frequently prescribed in pediatric oncology practice. However, excess or inappropriate use of antimicrobials is directly linked to the emergence of antimicrobial resistance. Although point-prevalence studies have examined the extent of antimicrobial use, a comprehensive qualitative evaluation of individual antimicrobial prescriptions remains lacking. Objective The aim of this study is to identify appropriate versus inappropriate antimicrobial use among pediatric cancer patients in a point-prevalence study, followed by an expert panel adjudication process and a subsequent report of these findings to participating centers. This study also aims to improve the quality of patient care by informing centers about discrepancies between internal standards of care and national guidelines. Methods Our point-prevalence study is performed at pediatric cancer centers in Germany and Austria. All patients under 18 years old who are hospitalized at the time of the study are included. As a supplement to the point-prevalence study, an expert panel is qualitatively assessing each of the antimicrobial prescriptions at the participating centers to review local guidelines and compare them with national guidelines. Results As of December 2021, the point-prevalence survey has been conducted at 30 sites and expert panel adjudication for qualitative assessment of each antimicrobial use is ongoing. Results of the study are expected in 2022. Conclusions This is the first point-prevalence study conducted among pediatric cancer centers with an integrated, multistep, qualitative approach that assesses each antimicrobial prescription. The results of this study will inform possible interventions for internal guidelines and antimicrobial stewardship programs implemented at pediatric cancer centers. In addition, local guidelines will be compared with national guidelines. Furthermore, this study will contribute to the overall integration of antimicrobial stewardship principles and initiatives in pediatric oncology and hematology, thereby improving safety and quality of care for children and adolescents with cancer and blood disorders. International Registered Report Identifier (IRRID) DERR1-10.2196/35774
Feeding dihydroquercetin in wheat-based diets to laying hens: impact on egg production and quality of fresh and stored eggs

ABSTRACT 1. This study assessed the impact of dietary dihydroquercetin (DHQ) in wheat-based diets on egg production, composition and quality when fed to laying hens. A total of 80 Hy-Line Brown hens were allocated to 20 enriched layer cages, over two tiers, in groups of four birds. 2. Two wheat-based diets were used in the study. A basal diet, meeting the nutrient requirement of the hens, containing 11.56 MJ/kg AME and 172 g/kg crude protein, was mixed and split into two parts. One part was fed as prepared to the control group of birds. The second diet was made by adding 1.5 g DHQ per kg basal diet and fed to the treatment group of birds. This level was relatively high and extended the data on levels normally fed. The diets were fed in a meal form and did not contain any coccidiostat, antimicrobial growth promoters or other similar additives. Each diet was fed to hens in 10 replicate cages for 4 weeks, from 22 to 26 weeks of age, following randomisation. 3. Subsequently, eggs were investigated to determine the impact of dietary DHQ on the quality variables of fresh and 28-d stored eggs. 4. Overall, feeding 1.5 g/kg dietary DHQ for 4 weeks did not affect (P > 0.05) egg production or the quality of fresh and stored eggs. Any observed egg quality changes (P < 0.05) confirmed the expected effects of egg storage.
Targeting mitochondrial metabolism for metastatic cancer therapy

Primary tumors evolve metabolic mechanisms favoring glycolysis for adenosine triphosphate (ATP) generation and antioxidant defenses. In contrast, metastatic cells frequently depend on mitochondrial respiration and oxidative phosphorylation (OxPhos). This reliance of metastatic cells on OxPhos can be exploited using drugs that target mitochondrial metabolism. Therefore, therapeutic agents that act via diverse mechanisms, including the activation of signaling pathways that promote the production of reactive oxygen species (ROS) and/or a reduction in antioxidant defenses may elevate oxidative stress and inhibit tumor cell survival. In this review, we will provide (1) a mechanistic analysis of function‐selective extracellular signal‐regulated kinase‐1/2 (ERK1/2) inhibitors that inhibit cancer cells through enhanced ROS, (2) a review of the role of mitochondrial ATP synthase in redox regulation and drug resistance, (3) a rationale for inhibiting ERK signaling and mitochondrial OxPhos toward the therapeutic goal of reducing tumor metastasis and treatment resistance. Recent reports from our laboratories using metastatic melanoma and breast cancer models have shown the preclinical efficacy of novel and rationally designed therapeutic agents that target ERK1/2 signaling and mitochondrial ATP synthase, which modulate ROS events that may prevent or treat metastatic cancer. These findings and those of others suggest that targeting a tumor's metabolic requirements and vulnerabilities may inhibit metastatic pathways and tumor growth. Approaches that exploit the ability of therapeutic agents to alter oxidative balance in tumor cells may be selective for cancer cells and may ultimately have an impact on clinical efficacy and safety. Elucidating the translational potential of metabolic targeting could lead to the discovery of new approaches for treatment of metastatic cancer.
Ensuring Care for Transgender Adolescents Who Need It: Response to ‘Reconsidering Informed Consent for Trans-Identified Children, Adolescents and Young Adults’

Abstract Adolescent transgender care is increasingly surrounded by controversies and criticism. One of these concerns expressed in a review article by Levine et al. entitled ‘Reconsidering Informed Consent for Trans-Identified Children, Adolescents and Young Adults’ is the limited evidence base, especially of the Dutch studies which provided the first and mostly cited basis for medical intervention at a young age. This Response is written by the first author of two of those studies that showed effectiveness of the approach that included puberty blockers. The author rebuts several of the concerns that Levine et al.have regarding these Dutch studies, among which are the limited statistical improvements of psychological measures, the use of the Utrecht Gender Dysphoria and the selection of participants. The author further refers to several shorter term longitudinal follow up studies that have been published, which are not mentioned by Levine et al. They also show improvement or stable psychological functioning and relief of gender incongruence. Finally, a careful evaluation and informed consent provision has always been recommended in all editions of the WPATH’s Standards of Care and are also part of the 8th version as well as the Endocrine Society guidelines. The author agrees therefore with Levine et al. that clinicians in transgender care should follow these international guidelines and provide such an assessment in order to ensure that medical interventions are appropriately provided for those transgender adolescents who need them.
Virologic and Immunologic Characterization of Coronavirus Disease 2019 Recrudescence After Nirmatrelvir/Ritonavir Treatment

Abstract We isolated a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BA.2 variant from a person with coronavirus disease 2019 recrudescence after nirmatrelvir/ritonavir treatment. Antiviral sensitivity and neutralizing antibody testing were performed with both parental SARS-CoV-2 and multiple variants of concern. We found that neither nirmatrelvir resistance nor absence of neutralizing immunity was a likely cause of the recrudescence.
Hydrophilic Crosslinked TEMPO‐Methacrylate Copolymers – a Straight Forward Approach towards Aqueous Semi‐Organic Batteries

Abstract Crosslinked hydrophilic poly(2,2,6,6‐tetramethylpiperidinyl‐N‐oxyl‐co‐[2‐(methacryloyloxy)‐ethyl]trimethyl ammonium chloride) [poly(TEMPO‐co‐METAC)] polymers with different monomer ratios are synthesized and characterized regarding a utilization as electrode material in organic batteries. These polymers can be synthesized rapidly utilizing commercial starting materials and reveal an increased hydrophilicity compared to the state‐of‐the‐art poly(2,2,6,6‐tetramethylpiperidinyl‐N‐oxyl‐4‐methacrylate) (PTMA). By increasing the hydrophilicity of the polymer, a preparation of cathode composites is enabled, which can be used for aqueous semi‐organic batteries. Detailed battery testing confirms that the additional METAC groups do not impair the battery behavior while enabling straight‐forward zinc‐TEMPO batteries.
Emergency Departments’ Uptake of Telehealth for Stroke Versus Pediatric Care: Observational Study

Background Telehealth for emergency stroke care delivery (telestroke) has had widespread adoption, enabling many hospitals to obtain stroke center certification. Telehealth for pediatric emergency care has been less widely adopted. Objective Our primary objective was to determine whether differences in policy or certification requirements contributed to differential uptake of telestroke versus pediatric telehealth. We hypothesized that differences in financial incentives, based on differences in patient volume, prehospital routing policy, and certification requirements, contributed to differential emergency department (ED) adoption of telestroke versus pediatric telehealth. Methods We used the 2016 National Emergency Department Inventory–USA to identify EDs that were using telestroke and pediatric telehealth services. We surveyed all EDs using pediatric telehealth services (n=339) and a convenience sample of the 1758 EDs with telestroke services (n=366). The surveys characterized ED staffing, transfer patterns, reasons for adoption, and frequency of use. We used bivariate comparisons to examine differences in reasons for adoption and use between EDs with only telestroke services, only pediatric telehealth services, or both. Results Of the 442 EDs surveyed, 378 (85.5%) indicated use of telestroke, pediatric telehealth, or both. EDs with both services were smaller in bed size, volume, and ED attending coverage than those with only telestroke services or only pediatric telehealth services. EDs with telestroke services reported more frequent use, overall, than EDs with pediatric telehealth services: 14.1% (45/320) of EDs with telestroke services reported weekly use versus 2.9% (8/272) of EDs with pediatric telehealth services (P<.001). In addition, 37 out of 272 (13.6%) EDs with pediatric telehealth services reported no consults in the past year. Across applications, the most frequently selected reason for adoption was “improving level of clinical care. ” Policy-related reasons (ie, for compliance with outside certification or standards or for improving ED performance on quality metrics) were rarely indicated as the most important, but these reasons were indicated slightly more often for telestroke adoption (12/320, 3.8%) than for pediatric telehealth adoption (1/272, 0.4%; P=.003). Conclusions In 2016, more US EDs had telestroke services than pediatric telehealth services; among EDs with the technology, consults were more frequently made for stroke than for pediatric patients. The most frequently indicated reason for adoption among all EDs was related to clinical care.