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Sterile alpha motif domain-containing proteins 9 and 9-like (SAMD9/9L) are associated with life-threatening genetic diseases in humans and are restriction factors of poxviruses. Yet, their cellular function and the extent of their antiviral role are poorly known. Here, we found that interferon-stimulated human SAMD9L restricts HIV-1 in the late phases of replication, at the posttranscriptional and prematuration steps, impacting viral translation and, possibly, endosomal trafficking. Surprisingly, the paralog SAMD9 exerted an opposite effect, enhancing HIV-1. More broadly, we showed that SAMD9L restricts primate lentiviruses, but not a gammaretrovirus (MLV), nor 2 RNA viruses (arenavirus MOPV and rhabdovirus VSV). Using structural modeling and mutagenesis of SAMD9L, we identified a conserved Schlafen-like active site necessary for HIV-1 restriction by human and a rodent SAMD9L. By testing a gain-of-function constitutively active variant from patients with SAMD9L-associated autoinflammatory disease, we determined that SAMD9L pathogenic functions also depend on the Schlafen-like active site. Finally, we found that the constitutively active SAMD9L strongly inhibited HIV, MLV, and, to a lesser extent, MOPV. This suggests that the virus-specific effect of SAMD9L may involve its differential activation/sensing and the virus ability to evade from SAMD9L restriction. Overall, our study identifies SAMD9L as an HIV-1 antiviral factor from the cell autonomous immunity and deciphers host determinants underlying the translational repression. This provides novel links and therapeutic avenues against viral infections and genetic diseases., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Legrand et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

ISG20 is an IFN-induced 3'-5' RNA exonuclease that acts as a broad antiviral factor. At present, the features that expose RNA to ISG20 remain unclear, although recent studies have pointed to the modulatory role of epitranscriptomic modifications in the susceptibility of target RNAs to ISG20. These findings raise the question as to how cellular RNAs, on which these modifications are abundant, cope with ISG20. To obtain an unbiased perspective on this topic, we used RNA-seq and biochemical assays to identify elements that regulate the behavior of RNAs against ISG20. RNA-seq analyses not only indicate a general preservation of the cell transcriptome, but they also highlight a small, but detectable, decrease in the levels of histone mRNAs. Contrarily to all other cellular ones, histone mRNAs are non-polyadenylated and possess a short stem-loop at their 3' end, prompting us to examine the relationship between these features and ISG20 degradation. The results we have obtained indicate that poly(A)-binding protein loading on the RNA 3' tail provides a primal protection against ISG20, easily explaining the overall protection of cellular mRNAs observed by RNA-seq. Terminal stem-loop RNA structures have been associated with ISG20 protection before. Here, we re-examined this question and found that the balance between resistance and susceptibility to ISG20 depends on their thermodynamic stability. These results shed new light on the complex interplay that regulates the susceptibility of different classes of viruses against ISG20., (© 2024 Louvat et al.)

Lassa fever hits West African countries annually in the absence of licensed vaccine to limit the burden of this viral hemorrhagic fever. We previously developed MeV-NP, a single-shot vaccine protecting cynomolgus monkeys against divergent strains one month or more than a year before Lassa virus infection. Given the limited dissemination area during outbreaks and the risk of nosocomial transmission, a vaccine inducing rapid protection could be useful to protect exposed people during outbreaks in the absence of preventive vaccination. Here, we test whether the time to protection can be reduced after immunization by challenging measles virus pre-immune male cynomolgus monkeys sixteen or eight days after a single shot of MeV-NP. None of the immunized monkeys develop disease and they rapidly control viral replication. Animals immunized eight days before the challenge are the best controllers, producing a strong CD8 T-cell response against the viral glycoprotein. A group of animals was also vaccinated one hour after the challenge, but was not protected and succumbed to the disease as the control animals. This study demonstrates that MeV-NP can induce a rapid protective immune response against Lassa fever in the presence of MeV pre-existing immunity but can likely not be used as therapeutic vaccine., (© 2023. The Author(s).)

Spatiotemporal data can be analyzed using spatial, time-series, and machine learning algorithms to extract regional biocrust trends. Analyzing the spatial trends of biocrusts through time, using satellite imagery, may improve the quantification and understanding of their change drivers. The current work strives to develop a unique framework for analyzing spatiotemporal trends of the spectral Crust Index (CI), thus identifying the drivers of the biocrusts' spatial and temporal patterns. To fulfill this goal, CI maps, derived from 31 annual Landsat images, were analyzed by applying advanced statistical and machine learning algorithms. A comprehensive overview of biocrusts' spatiotemporal patterns was achieved using an integrative approach, including a long-term analysis, using the Mann-Kendall (MK) statistical test, and a short-term analysis, using a rolling MK with a window size of five years. Additionally, temporal clustering, using the partition around medoids (PAM) algorithm, was applied to model the spatial multi-annual dynamics of the CI. A Granger Causality test was then applied to quantify the relations between CI dynamics and precipitation. The findings show that 88.7% of pixels experienced a significant negative change, and only 0.5% experienced a significant positive change. A strong association was found in temporal trends among all clusters (0.67 ≤ r ≤ 0.8), signifying a regional effect due to precipitation levels (p < 0.05 for most clusters). The biocrust dynamics were also locally affected by anthropogenic factors (0.58 > CI > 0.64 and 0.64 > CI > 0.71 for strongly and weakly affected regions, respectively). A spatiotemporal analysis of a series of spaceborne images may improve conservation management by evaluating biocrust development in drylands. The suggested framework may also by applied to various disciplines related to quantifying spatial and temporal trends., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Many bariatric surgeons test the anastomosis and staple lines with some sort of provocative test. This can take the form of an air leak test with a nasogastric tube with methylene blue dye or with an endoscopy. The State Department of Health Statistics in Texas tracks outcomes using the Texas Public Use Data File (PUDF)., Methods: We queried the Texas Inpatient and Outpatient PUDFs for 2013 to 2017 to examine the number of bariatric surgeries with endoscopy performed at the same time. We used the International Classification of Diseases Clinical Modification Version 9 (ICD-9-CM) and ICD-10 procedure codes and Current Procedural Terminology for Sleeve Gastrectomy (SG) and laparoscopic Roux-en-Y gastric bypass (LRYGB) and endoscopy, and the ICD-9-CM and ICD-10 diagnosis codes for morbid obesity., Results: There were 74,075 SG reported in the Texas Inpatient and Outpatient PUDF for the years 2013-2017. Of the SG performed, 5,521 (7.4%) had an intraoperative endoscopy. For the 19,192 LRYGB reported, 1640 (8.6%) underwent LRYGB + endoscopy. This was broken down by SG only vs SG + endoscopy and LRYGB only vs LRYGB + endoscopy. Overall, SG + endoscopy had a significantly shorter length of stay (LOS) vs LRYGB + endoscopy at 1.74 d vs 2.34 d ( P < .001) and a significantly less cost of $71,685 vs $91,093 ( P < .001)., Conclusions: A small percentage of SG and LRYGB patients underwent endoscopy for provocative testing over the study period. Provocative testing with endoscopy costs more for SG and LRYGB and was associated with a shorter LOS., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest directly relevant to the content of this article., (© 2020 by JSLS, Journal of the Society of Laparoscopic & Robotic Surgeons.)

Hematopoietic cell transplantation (HCT) affords curative potential for high-risk patients but also carries risk of morbidity and mortality. Early palliative care (PC) integration can aid in supporting patients and families, fostering goal-directed care, and maximizing quality-of-life throughout. However, little is known about patient and family hopes, worries, goals, or values in pediatric HCT. Through retrospective review of pretransplant PC consultations, this study sought to provide insights from this unique patient population. Across 100 initial PC encounters conducted between December 2015 and March 2018, patient and caregiver responses to five targeted questions were extracted and analyzed. Data analysis revealed themes related to patient quality-of-life, caregiver/parent role, hopes, and worries. The most commonly identified thematic responses within each topic area were patient quality-of-life "electronics/entertainment" (49%), caregiver/parent role "doing right by my child" (58%), hopes "cure" (83%), worries "potential side effects" (43%), other spirituality (34%), and resiliency (29%). These findings provide an understanding of the values, goals, priorities, hopes, and fears experienced by pediatric HCT patients and their families, which may help inform a targeted approach to improve communication and overall care throughout transplantation. Variability was noted, underscoring the importance of fostering flexible, patient/family-centered communication beginning in the pretransplant period.

Introduction: Mindfulness-based therapies are rooted in the Buddhist tradition, and promote cultivation of qualities such as open awareness, acceptance and compassion. While various studies have demonstrated the efficacy of integrating mindfulness in therapeutic practice for people suffering from clinical conditions such as depression and anxiety as well as the non-clinical population, this was rarely replicated in Israel. In the Mindfulness Clinic, located in the Mental Health Center, Beer Sheva, mindfulness workshops are now available for diverse populations dealing with various challenges such as daily stress, chronic pain, and depression., Aims: This article aims to describe the effects of mindfulnessbased workshops in a mixed sample, via the examination of various outcome variables such as quality of life, depression and anxiety symptoms, mindfulness, self-compassion and self-criticism., Methods: Self-report questionnaires provided before and after the workshop., Results: Results: Preliminary results demonstrated that among 18 participants in mindfulness workshops during the period November 2013 till March 2014, a significant improvement was observed for most of the variables. In addition, effect sizes were measured, demonstrating medium to large effects, with the largest effect size for self-compassion., Discussion: These preliminary results demonstrate the time limited efficacy of Mindfulness Workshops in a mixed sample. In addition, it is conceivable that mindfulness-based workshop may provide an effective preventive and/or therapeutic approach for people living in the south of Israel, who were facing an ongoing rackets' threat in recent years. In the future, this hypothesis should be examined empirically.

Endothermic arousal from torpor is an energetically costly process and imposes enormous demands on the cardiovascular system, particularly during early stage arousal from low body temperature (Tb). To minimize these costs many bats and other heterothermic endotherms rewarm passively from torpor using solar radiation or fluctuating ambient temperature (Ta). Because the heart plays a critical role in the arousal process in terms of blood distribution and as a source of heat production, it is desirable to understand how the function of this organ responds to passive rewarming and how this relates to changes in metabolism and Tb. We investigated heart rate (HR) in hibernating long-eared bats (Nyctophilus gouldi) and its relationship to oxygen consumption (V̇o₂) and subcutaneous temperature (Tsub) during exposure to increasing Ta compared with endogenous arousals at constant low Ta. During passive rewarming, HR and V̇o₂ remained low over a large Tsub range and increased concurrently with increasing Ta (Q₁₀ 2.4 and 2.5, respectively). Absolute values were higher than during steady-state torpor but below those measured during torpor entry. During active arousals, mean HR and V̇o₂ were substantially higher than during passive rewarming at corresponding Tsub. In addition, partial passive rewarming reduced the cost of arousal from torpor by 53% compared with entirely active arousal. Our data show that passive rewarming considerably reduces arousal costs and arousal time; we suggest this may also contribute to minimizing exposure to oxidative stresses as well as demands on the cardiovascular system., (Copyright © 2015 the American Physiological Society.)

Background: Paediatric low-grade gliomas (LGGs) encompass a heterogeneous set of tumours of different histologies, site of lesion, age and gender distribution, growth potential, morphological features, tendency to progression and clinical course. Among LGGs, Pilocytic astrocytomas (PAs) are the most common central nervous system (CNS) tumours in children. They are typically well-circumscribed, classified as grade I by the World Health Organization (WHO), but recurrence or progressive disease occurs in about 10-20% of cases. Despite radiological and neuropathological features deemed as classic are acknowledged, PA may present a bewildering variety of microscopic features. Indeed, tumours containing both neoplastic ganglion and astrocytic cells occur at a lower frequency., Methods: Gene expression profiling on 40 primary LGGs including PAs and mixed glial-neuronal tumours comprising gangliogliomas (GG) and desmoplastic infantile gangliogliomas (DIG) using Affymetrix array platform was performed. A biologically validated machine learning workflow for the identification of microarray-based gene signatures was devised. The method is based on a sparsity inducing regularization algorithm l₁l₂ that selects relevant variables and takes into account their correlation. The most significant genetic signatures emerging from gene-chip analysis were confirmed and validated by qPCR., Results: We identified an expression signature composed by a biologically validated list of 15 genes, able to distinguish infratentorial from supratentorial LGGs. In addition, a specific molecular fingerprinting distinguishes the supratentorial PAs from those originating in the posterior fossa. Lastly, within supratentorial tumours, we also identified a gene expression pattern composed by neurogenesis, cell motility and cell growth genes which dichotomize mixed glial-neuronal tumours versus PAs. Our results reinforce previous observations about aberrant activation of the mitogen-activated protein kinase (MAPK) pathway in LGGs, but still point to an active involvement of TGF-beta signaling pathway in the PA development and pick out some hitherto unreported genes worthy of further investigation for the mixed glial-neuronal tumours., Conclusions: The identification of a brain region-specific gene signature suggests that LGGs, with similar pathological features but located at different sites, may be distinguishable on the basis of cancer genetics. Molecular fingerprinting seems to be able to better sub-classify such morphologically heterogeneous tumours and it is remarkable that mixed glial-neuronal tumours are strikingly separated from PAs.

The characterization of proteins via liquid chromatography-mass spectrometry (LC-MS) and tandem MS is a challenge due to the large dynamic range and the high complexity of the molecules of interest. In LC-MS experiments, the inconsistent variation in the travel time of analytes in the LC column results in nonlinear shifts in the LC retention time (RT). This variability must be corrected to accurately match corresponding peptide features across samples in LC-MS experiments. Standard methods for RT alignment applied to the raw data are computationally expensive, making it impractical to process a large number of samples. More successful algorithms perform the alignment on features that matched across experiments based on pre-specified mass and RT windows. Features that match across multiple experiments are more likely to be true positives and, therefore, will be more suitable to drive the alignment correction. However, depending on the feature matching algorithm, ambiguities can arise when more than one candidate feature match falls within the specified windows which might affect the alignment performance. In addition, some of the feature-based alignment algorithms do not correct for nonlinear RT shifts. We propose a novel feature matching algorithm that incorporates wavelet-based shape information about the features. We tested our algorithm on two different applications of MS. First, we combined the feature matching algorithm with a robust nonparametric kernel-type regression to form a nonlinear feature-based alignment framework for LC-MS experiments. We validated our alignment framework on LC-MS data from complex samples with known spiked-in proteins, demonstrating our ability to correctly identify each of them with higher reproducibility and probability score when comparing with the SuperHirn software. In addition, by using our feature-based alignment framework, we were able to increase the number of matched features and improve the correlation between replicates. Second, we tested our feature matching algorithm on MALDI MS with MS/MS acquisitions. We found that using only features that matched across replicates of tandem mass spectra we could improve the identification of peptides compared with the current state-of-the-art software. Supplementary Material is available online at www.libertonline.com/cmb ., (© Mary Ann Liebert, Inc.)

Finding new peptide biomarkers for stomach cancer in human sera that can be implemented into a clinically practicable prediction method for monitoring of stomach cancer. We studied the serum peptidome from two different biorepositories. We first employed a C8-reverse phase liquid chromatography approach for sample purification, followed by mass-spectrometry analysis. These were applied onto serum samples from cancer-free controls and stomach cancer patients at various clinical stages. We then created a bioinformatics analysis pipeline and identified peptide signature discriminating stomach adenocarcinoma patients from cancer-free controls. Matrix Assisted Laser Desorption/Ionization-Time of Flight (MALDI-TOF) results from 103 samples revealed 9 signature peptides; with prediction accuracy of 89% in the training set and 88% in the validation set. Three of the discriminating peptides discovered were fragments of Apolipoproteins C-I and C-III (apoC-I and C-III); we further quantified their serum levels, as well as CA19-9 and CRP, employing quantitative commercial-clinical assays in 142 samples. ApoC-I and apoC-III quantitative results correlated with the MS results. We then employed apoB-100-normalized apoC-I and apoC-III, CA19-9 and CRP levels to generate rules set for stomach cancer prediction. For training, we used sera from one repository, and for validation, we used sera from the second repository. Prediction accuracies of 88.4% and 74.4% were obtained in the training and validation sets, respectively. Serum levels of apoC-I and apoC-III combined with other clinical parameters can serve as a basis for the formulation of a diagnostic score for stomach cancer patients.

Background: The structural stability of peptides in solution strongly affects their binding affinities and specificities. Thus, in peptide biotechnology, an increase in the structural stability is often desirable. The present work combines two orthogonal computational techniques, Molecular Dynamics and a knowledge-based potential, for the prediction of structural stability of short peptides (< 20 residues) in solution., Results: We tested the new approach on four families of short beta-hairpin peptides: TrpZip, MBH, bhpW and EPO, whose structural stabilities have been experimentally measured in previous studies. For all four families, both computational techniques show considerable correlation (r > 0.65) with the experimentally measured stabilities. The consensus of the two techniques shows higher correlation (r > 0.82)., Conclusion: Our results suggest a prediction scheme that can be used to estimate the relative structural stability within a peptide family. We discuss the applicability of this predictive approach for in-silico screening of combinatorial peptide libraries.

Motivation: Mass spectrometry (MS) is increasingly being used for biomedical research. The typical analysis of MS data consists of several steps. Feature extraction is a crucial step since subsequent analyses are performed only on the detected features. Current methodologies applied to low-resolution MS, in which features are peaks or wavelet functions, are parameter-sensitive and inaccurate in the sense that peaks and wavelet functions do not directly correspond to the underlying molecules under observation. In high-resolution MS, the model-based approach is more appealing as it can provide a better representation of the MS signals by incorporating information about peak shapes and isotopic distributions. Current model-based techniques are computationally expensive; various algorithms have been proposed to improve the computational efficiency of this paradigm. However, these methods cannot deal well with overlapping features, especially when they are merged to create one broad peak. In addition, no method has been proven to perform well across different MS platforms., Results: We suggest a new model-based approach to feature extraction in which spectra are decomposed into a mixture of distributions derived from peptide models. By incorporating kernel-based smoothing and perceptual similarity for matching distributions, our statistical framework improves existing methodologies in terms of computational efficiency and the accuracy of the results. Our model is parameterized by physical properties and is therefore applicable to different MS instruments and settings. We validate our approach on simulated data, and show that the performance is higher than commonly used tools on real high- and low-resolution MS, and MS/MS data sets.

Despite advances in the investigation and treatment of angina and myocardial infarction, and increased knowledge of the factors associated with the development and progression of ischaemic heart disease, it remains the leading cause of death and morbidity in the majority of industrialized countries. Cardiac rehabilitation provides a means of modifying lifestyle and other risk factors in patients presenting with established, symptomatic coronary artery disease, thereby reducing the risk of further cardiac events. It has also been proven to be cost-efficient.

Diabetes mellitus affects 2% of the population and up to 5% of people over 65 years of age (Thomas, 1993). Diabetic patients have more coronary artery disease and a higher mortality from acute myocardial infarction (AMI) than the rest of the population (Patmore and Jennings, 1996). They have similar-size infarcts to those without diabetes, but the total mortality post-MI is higher (Karlson et al, 1993). This article examines the literature on AMI in diabetic patients to ascertain the most effective management of these patients and hence improve their prognosis.

The drug knowledge of 107 patients was determined before and after entering a self-medication scheme on the post-coronary care unit (PCCU) at City Hospital, Birmingham, and approximately 6 weeks post-discharge when these patients attended their cardiac rehabilitation classes. Fifty-two completed questionnaires were returned. The results indicated a general increase in patients knowledge about the names and side-effects of their drugs, the times at which they take them and the reasons for taking them, following self-medication. A smaller number of questionnaires (19) were completed 6 weeks after discharge. The responses to these suggested that patients who self-medicated in hospital showed greater drug knowledge, especially with regard to potential side-effects, than those who had not. Patients' confidence in their ability to self-medicate safely at home showed no relation to their actual knowledge. It is suggested that self-medication on the PCCU is an important part of the cardiac rehabilitation programme.