Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of Killer Cell Immunoglobulin-Like Receptors and Their HLA-Ligands with Type 1 Diabetes Among South Indian Population

ABSTRACT Background Type 1 diabetes (T1D) is a multifactorial autoimmune disease, involving strong genetic components with familial predisposition. Killer cell immunoglobulin-like receptors (KIRs) found on the surface of NK cells have ligands of human leukocyte antigen (HLA) class I that are associated with T1D. The present study evaluates the influence of KIR genes and their HLA-ligands in the aetiology of T1D among the South Indian population. Methods A total of 125 T1D patients, along with their parents (n = 126) and siblings (n = 52) were recruited. PCR-based genotyping was performed for KIR genes and HLA class I ligands. The gene frequencies were compared between patients and siblings/parents. Linkage-disequilibrium (LD) analysis was performed to assess the genetic association between KIR gene pairs. Results The results show significant differences in HLA-ligands of KIR genes between patients and parents. The HLA-C1C1 homozygosity was found to be a predisposing risk factor, and HLA-C1C2 heterozygosity was protective towards T1D along with either the activating KIR2DS2 or inhibitory KIRs 2DL1, 2DL2, 2DL3. However, the frequency of inhibitory KIR3DL1 significantly increased in the presence of HLA-B Bw4 Ile80 in parents when compared to patients showing a protective effect on T1D. Two pairs of KIR genes, 2DS4-3DL1 and 2DS1-2DL5, showed strong LD in patients, siblings and parents. Conclusion The KIR-HLA ligand combinations have a significant effect on T1D aetiology among the South Indian population. This study defines a pattern for family-based association studies with genotypic information about KIR genes and their HLA-ligands, providing the first evidence towards T1D among the South Indian population.
Predictive modeling of concentration-dependent viscosity behavior of monoclonal antibody solutions using artificial neural networks

ABSTRACT Solutions of monoclonal antibodies (mAbs) can show increased viscosity at high concentration, which can be a disadvantage during protein purification, filling, and administration. The viscosity is determined by protein-protein-interactions, which are influenced by the antibody’s sequence as well as solution conditions, like pH, buffer type, or the presence of salts and other excipients. To predict viscosity, experimental parameters, like the diffusion interaction parameter (kD), or computational tools harnessing information derived from primary sequence, are often used, but a reliable predictive tool is still missing. We present a modeling approach employing artificial neural networks (ANNs) using experimental factors combined with simulation-derived parameters plus viscosity data from 27 highly concentrated (180 mg/mL) mAbs. These ANNs can be used to predict if mAbs exhibit problematic viscosity at distinct concentrations or to model viscosity-concentration-curves.
Targeting Ara h 2 with human‐derived monoclonal antibodies prevents peanut‐induced anaphylaxis in mice

Peanut allergy is a type‐I hypersensitivity immune reaction mediated by the binding of peanut allergens to IgE‐FcεRI complexes on mast cells and basophils and by their subsequent cellular degranulation. Of all major peanut allergens, Ara h 2 is considered the most anaphylactic. With few options but allergen avoidance, effective treatment of allergic patients is needed. Passive immunotherapy (herein called PIT) based on prophylactic administration of peanut‐specific monoclonal antibodies (mAbs) may present a promising treatment option for this under‐served disease.
Radiometric correction of C-band imagery for topographic effects in regions of moderate relief

The combined effects of topography, slope, look angle, and aspect on C-band synthetic-aperture radar (SAR) data on the radiometric quality of SAR images in a region of moderate relief are examined. A correction method was used to attenuate the change of illumination across the swath due to the antenna pattern. Ground data were integrated into the analysis using a digital terrain model (DTM). Correction functions based on the cosine of the incidence angle were applied to the thematic classes and to the grouped classes in order to reduce the effects related to topography. It was found that it is possible to eliminate part of the radiometric variations created by moderate topographic relief. After the corrections were applied, a reduction was noted of the variance in the radiometric values of the spectral signatures of the cover types, which ranged between 3.03% and 9.47%, depending on the correction function used. >
A gravity‐wave induced quasi‐biennial oscillation in a three‐dimensional mechanistic model

Previous two‐dimensional model simulations using the Hines parametrization of unresolved gravity waves have produced long‐period oscillations in the tropics. Such oscillations include the quasi‐biennial oscillation (QBO) and the semi‐annual oscillation (SAO). In this paper simulations with a three‐dimensional mechanistic model are reported which show an even more realistic representation of the QBO. These simulations show the expected dependence of the period of the QBO on the momentum flux entering the stratosphere, but also show a hitherto unreported dependency of the period on the upper boundary condition. In these simulations the dependency is linked to changes in mesospheric vertical velocities associated with the SAO.
Multiplication and inversion over a class of GF(2/sup m/)

Finite fields GF(2/sup m/) generated by irreducible all one polynomials are considered. Field elements are represented by a canonical basis. For such representation, a structure for parallel multiplier is presented. The structure is modular, and suitable for VLSI implementation. Sequential computation of inverses of the field elements is also considered and a high-speed configuration is presented. <<ETX>>
Domain generation algorithms detection with feature extraction and Domain Center construction

Network attacks using Command and Control (C&C) servers have increased significantly. To hide their C&C servers, attackers often use Domain Generation Algorithms (DGA), which automatically generate domain names for C&C servers. Researchers have constructed many unique feature sets and detected DGA domains through machine learning or deep learning models. However, due to the limited features contained in the domain name, the DGA detection results are limited. In order to overcome this problem, the domain name features, the Whois features and the N-gram features are extracted for DGA detection. To obtain the N-gram features, the domain name whitelist and blacklist substring feature sets are constructed. In addition, a deep learning model based on BiLSTM, Attention and CNN is constructed. Additionally, the Domain Center is constructed for fast classification of domain names. Multiple comparative experiment results prove that the proposed model not only gets the best Accuracy, Precision, Recall and F1, but also greatly reduces the detection time.
Immune Checkpoint Inhibitors in Solid Organ Transplant Recipients With Advanced Skin Cancers—Emerging Strategies for Clinical Management

Use of immune checkpoint inhibitors (ICIs) in solid organ transplant recipients (SOTRs) with advanced skin cancers presents a significant clinical management dilemma. SOTRs and other immunosuppressed patients have been routinely excluded from ICI clinical trials with good reason: immune checkpoints play an important role in self- and allograft-tolerance and risk of acute allograft rejection reported in retrospective studies affects 10% to 65% of cases. These reports also confirm that cutaneous squamous cell carcinoma and melanoma respond to ICI therapy, although response rates are generally lower than those observed in immunocompetent populations. Prospective trials are now of critical importance in further establishing ICI efficacy and safety. However, based on current knowledge, we recommend that ICIs should be offered to kidney transplant recipients with advanced cutaneous squamous cell carcinoma, melanoma, or Merkel cell carcinoma if surgery and/or radiotherapy have failed. For kidney transplant recipients, this should be first line ahead of chemotherapy and targeted therapies. In SOTRs, the use of ICIs should be carefully considered with the benefits of ICIs versus risks of allograft rejection weighed up on a case-by-case basis as part of shared decision-making with patients. In all cases, parallel management of immunosuppression may be key to ICI responsiveness. We recommend maintaining immunosuppression before ICI initiation with a dual immunosuppressive regimen combining mammalian target of rapamycin inhibitors and either corticosteroids or calcineurin inhibitors. Such modification of immunosuppression must be considered in the context of allograft risk (both rejection and also its subsequent treatment) and risk of tumor progression. Ultimately, a multidisciplinary approach should underpin all clinical decision-making in this challenging scenario.
Is there a benefit for anesthesiologists of adding difficult airway scenarios for learning fiberoptic intubation skills using virtual reality training? A randomized controlled study

Fiberoptic intubation for a difficult airway requires significant experience. Traditionally only normal airways were available for high fidelity bronchoscopy simulators. It is not clear if training on difficult airways offers an advantage over training on normal airways. This study investigates the added value of difficult airway scenarios during virtual reality fiberoptic intubation training. A prospective multicentric randomized study was conducted 2019 to 2020, among 86 inexperienced anesthesia residents, fellows and staff. Two groups were compared: Group N (control, n = 43) first trained on a normal airway and Group D (n = 43) first trained on a normal, followed by three difficult airways. All were then tested by comparing their ORSIM® scores on 5 scenarios (1 normal and 4 difficult airways). The final evaluation ORSIM® score for the normal airway testing scenario was significantly higher for group N than group D: median score 76% (IQR 56.5–90) versus 58% (IQR 51.5–69, p = 0.0039), but there was no difference in ORSIM® scores for the difficult intubation testing scenarios. A single exposure to each of 3 different difficult airway scenarios did not lead to better fiberoptic intubation skills on previously unseen difficult airways, when compared to multiple exposures to a normal airway scenario. This finding may be due to the learning curve of approximately 5–10 exposures to a specific airway scenario required to reach proficiency.
Exploring dissections of rectangles into right-angled triangles

In this article we highlight how a simple classroom activity associated with the dissection of rectangles into right-angled triangles can lead on to a number of interesting explorations for students following a post-16 mathematics course. Several results connected with this construction are obtained, and some of the educational benefits of carrying out an investigation such as this are also discussed.
Cooling of low-mass carbon-oxygen dwarfs from the planetary nucleus stage through the crystallization stage

The evolution of a carbon-oxygen dwarf of mass Mroughly-equal0.6 Msun has been carried all the way from an initial nuclear burning stage, when it is the central star of a planetary nebula, to the stage of complete internal crystallization, after 10/sup 10/ yr of cooling. Shell hydrogen and helium burning, neutrino losses, and the effects of liquification and crystallization have been taken into account. We show how the luminosity-time relationship may be understood in terms of balances between competing physical processes and demonstrate that, after complete crystallization, the time scale for cooling to terrestrial-like temperatures, in our approximation, is simply the optical depth of the outer, nonisothermal layer multiplied by a dimensional constant which, in years, is of the order of unity. A luminosity function based on the results covers the range -5< or approx. =log(L/Lsun)< or approx. =4 and agrees reasonably well with the observed luminosity function extending from the brighest planetary nebula nuclei to the dimmest observed white dwarfs, except perhaps for log(L/L/sub sun/)< or approx. =-4.5. Possible reasons for the apparent discrepancy at low luminosity, apart from the extreme obstacles against discovery, are discussed, one of the simplest is that the oldest dwarfs in the solar vicinitymore » are distributed over a distance from the galactic plane that is approx.5 times larger than is the case for the youngest dwarfs; another possibility is that the opacity in the outer layers of the oldest dwarf models has been overestimated (or underestimatedexclamation) by a factor of 5 or more. « less
NE‐RDFE: A protocol and toolkit for computing relative dissociation free energies with GROMACS between dissimilar molecules using bidirectional nonequilibrium dual topology schemes

We describe a step‐by‐step protocol and toolkit for the computation of the relative dissociation free energy (RDFE) with the GROMACS molecular dynamics package, based on a novel bidirectional nonequilibrium alchemical approach. The proposed methodology does not require any intervention on the code and allows computing with good accuracy the RDFE between small molecules with arbitrary differences in volume, charge, and chemical topology. The procedure is illustrated for the challenging SAMPL9 batch of host–guest pairs. The article is supplemented by a detailed online tutorial, available at https://procacci.github. io/vdssb_gromacs/NE-RDFE and by a public Zenodo repository available at https://zenodo.org/record/6982932.
Fully Automatic Method for Reliable Spinal Cord Compartment Segmentation in Multiple Sclerosis

BACKGROUND AND PURPOSE: Fully automatic quantification methods of spinal cord compartments are needed to study pathologic changes of the spinal cord GM and WM in MS in vivo. We propose a novel method for automatic spinal cord compartment segmentation (SCORE) in patients with MS. MATERIALS AND METHODS: The cervical spinal cords of 24 patients with MS and 24 sex- and age-matched healthy controls were scanned on a 3T MR imaging system, including an averaged magnetization inversion recovery acquisition sequence. Three experienced raters manually segmented the spinal cord GM and WM, anterior and posterior horns, gray commissure, and MS lesions. Subsequently, manual segmentations were used to train neural segmentation networks of spinal cord compartments with multidimensional gated recurrent units in a 3-fold cross-validation fashion. Total intracranial volumes were quantified using FreeSurfer. RESULTS: The intra- and intersession reproducibility of SCORE was high in all spinal cord compartments (eg, mean relative SD of GM and WM: ≤ 3.50% and ≤1.47%, respectively) and was better than manual segmentations (all P < .001). The accuracy of SCORE compared with manual segmentations was excellent, both in healthy controls and in patients with MS (Dice similarity coefficients of GM and WM: ≥ 0.84 and ≥0.92, respectively). Patients with MS had lower total WM areas (P < .05), and total anterior horn areas (P < .01 respectively), as measured with SCORE. CONCLUSIONS: We demonstrate a novel, reliable quantification method for spinal cord tissue segmentation in healthy controls and patients with MS and other neurologic disorders affecting the spinal cord. Patients with MS have reduced areas in specific spinal cord tissue compartments, which may be used as MS biomarkers.
Semismooth Newton methods for variational problems with inequality constraints

Inequality constraints occur in many different fields of application, e.g., in structural mechanics, flow processes in porous media or mathematical finance. In this paper, we make use of the mathematical structure of these conditions in order to obtain an abstract computational framework for problems with inequality conditions. The constraints are enforced locally by means of Lagrange multipliers which are defined with respect to dual basis functions. The reformulation of the inequality conditions in terms of nonlinear complementarity functions leads to a system of semismooth nonlinear equations that is solved by a generalized version of Newton's method for semismooth problems. By this, both nonlinearities in the pde model and inequality constraints are treated within a single Newton iteration which converges locally superlinear. The scheme can efficiently be implemented in terms of an active set strategy with local static condensation of the non‐essential variables. Numerical examples from different fields of application illustrate the generality and the robustness of the method (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Crisis Response and Suicidal Behaviors of Essential Workers and Children of Essential Workers During the COVID-19 Pandemic

Objective: The COVID-19 pandemic has put unprecedented stress on essential workers and their children. Limited cross-sectional research has found increases in mental health conditions from workload, reduced income, and isolation among essential workers. Less research has been conducted on children of essential workers. We examined trends in the crisis response of essential workers and their children from April 2020 through August 2021. Methods: We investigated the impact during 3 periods of the pandemic on workers and their children using anonymized data from the Crisis Text Line on crisis help-seeking texts for thoughts of suicide or active suicidal ideation (desire, intent, capability, time frame), abuse (emotional, physical, sexual, unspecified), anxiety/stress, grief, depression, isolation, bullying, eating or body image, gender/sexual identity, self-harm, and substance use. We used generalized estimating equations to study the longitudinal change in crisis response across the later stages of the pandemic using adjusted odds ratios (aORs) for worker status and crisis outcomes. Results: Results demonstrated higher odds of crisis outcomes for thoughts of suicide (aOR = 1.06; 95% CI, 1.00-1.12) and suicide capability (aOR = 1.14; 95% CI, 1.02-1.27) among essential workers than among nonessential workers. Children of essential workers had higher odds of substance use than children of nonessential workers (aOR = 1.33; 95% CI, 1.08-1.65), particularly for Indigenous American children (aOR = 2.76; 95% CI, 1.35-5.36). Essential workers (aOR = 1.17; 95% CI, 1.07-1.27) and their children (aOR = 1.18; 95% CI, 1.07-1.30) had higher odds of grief than nonessential workers and their children. Conclusion: Essential workers and their children had elevated crisis outcomes. Immediate and low-cost psychologically supportive interventions are needed to mitigate the mental health impacts of the COVID-19 pandemic on these populations.
Clinical Utility of WAIS-IV Matrix Reasoning Among Adult Low Educated Recent Immigrants; A Note of Caution.

OBJECTIVE To examine the clinical utility of Wechsler Adult Intelligence Scale-IV (WAIS-IV) Matrix Reasoning in limited educated recently arrived immigrants in Denmark. METHOD Participants were 64 limited educated (0-9 years' education) independently living adult immigrants primarily from Middle Eastern and Sub-Saharan African countries who completed WAIS-IV Matrix Reasoning as well as demographic, and medical questionnaires. RESULTS Thirty-eight participants (59%) scored more than two standard deviations below the Scandinavian mean (scaled score < 4). Performances were significantly associated with years of education but not with occupational status, years of residence in Denmark, or Danish language skills. The most common error types were repetition errors (15.84%) and incomplete correlate errors (10.47%), with a strong trend for a higher proportion of repetition errors in participants with <5 years of education. CONCLUSIONS The findings indicate that WAIS-IV Matrix Reasoning underestimates cognitive functioning in limited educated recently arrived immigrants, thus calling its clinical utility into question.
Unraveling the kinetochore nanostructure in Schizosaccharomyces pombe using multi-color SMLM imaging

Virant et al. build an in situ model of the Schizosaccharomyces pombe kinetochore by determining inter-protein distances and copy numbers. Next to confirming its conserved nature known from in vitro data, they point out S. pombe specifics, e.g., within DASHc and the inner kinetochore structure.
Is there a relationship between surgical volume and outcome for total elbow arthroplasty? A systematic review

Purpose: Total elbow arthroplasty (TEA) is rarely performed compared to other arthroplasties. For many surgical procedures, literature shows better outcomes when they are performed by experienced surgeons and in so-called ‘high-volume’ hospitals. We systematically reviewed the literature on the relationship between surgical volume and outcomes following TEA. Methods: A literature search was performed using the MEDLINE, EMBASE and CINAHL databases. The literature was systematically reviewed for original studies comparing TEA outcomes among hospitals or surgeons with different annual or career volumes. For each study, data were collected on study design, indications for TEA, number of included patients, implant types, cut-off values for volume, number and types of complications, revision rate and functional outcome measures. The methodological quality of the included studies was assessed using the Newcastle–Ottawa Scale. Results: Two studies, which included a combined 2301 TEAs, found that higher surgeon volumes were associated with lower revision rates. The examined complication rates did not differ between high- and low-volume surgeons. In one study, low-hospital volume is associated with an increased risk of revision compared to high-volume hospitals, but for other complication types, no difference was found. Conclusions: Based on the results, the evidence suggests that high-volume centers have a lower revision rate in the long term. No minimum amount of procedures per year can be advised, as the included studies have different cut-off values between groups. As higher surgeon- and center-volume, (therefore presumably experience) appear to yield better outcomes, centralization of total elbow arthroplasty should be encouraged.
IT COULD BE WORSE: A RARE CASE OF SPONTANEOUS CHOLEDOCHODUODENAL FISTULA WITH SUCCESSFUL DRAINAGE TO RELIEVE ACUTE SEVERE CHOLANGITIS

Correspondence to: Chunhua Wang, MD, Department of Gastroenterology, the 980th Hospital of the People’s Liberation Army Joint Service (Bethune International Peace Hospital), No. 398 of Zhongshan West St, Shijiazhuang, Hebei, 050082, China (hpyykyzy@163.com or crown99@126.com). IT COULD BE WORSE: A RARE CASE OF SPONTANEOUS CHOLEDOCHODUODENAL FISTULA WITH SUCCESSFUL DRAINAGE TO RELIEVE ACUTE SEVERE CHOLANGITIS