bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Association Between Sleep Disturbance and Proinflammatory Markers in Patients With Cancer
Authors: Tong Huan-huan , Li Jing-ru , Feng Yuan , Li Shu-wen , Qiu Huan , Hong Jing-fang 
Published: March 2022

Background
Sleep disturbance is one of the symptoms with high incidence and negative influence in patients with cancer. A better understanding of the biological factors associated with sleep disturbance is critical to predict, treat, and manage this condition.

Objective
The aim of this study was to determine the correlation between sleep disturbance and proinflammatory markers in adult patients with cancer.

Methods
A systematic search was conducted in 7 databases from inception to March 1, 2020, for this meta-analysis. Two reviewers independently screened the studies, extracted data, and appraised the quality of the studies. Meta-analyses were conducted using Stata 12.0 software.

Results
Sixteen studies were included. Results indicated that sleep disturbance was associated with higher levels of the overall proinflammatory markers and that the effect size was small yet significant. Further subgroup analyses suggested that sleep disturbance was significantly associated with interleukin-6 and C-reactive protein, but not with interleukin-1β or tumor necrosis factor-α. Meta-regression results indicated that only the sample source affected the association between sleep disturbance and proinflammatory markers.

Conclusion
There was a positive relationship between sleep disturbance and selected proinflammatory markers in adult patients with cancer.

Implication for Practice
This review provides empirical support for the association between sleep disturbance and certain proinflammatory markers. Healthcare providers can further explore specific biomarkers to precisely identify the individuals at risk of sleep disturbance and develop targeted strategies for therapeutic and clinical interventions.
Nonopioid drug combinations for cancer pain: a systematic review
Authors: Sohi Gursharan , Lao Nicholas , Caraceni Augusto , Moulin Dwight E. , Zimmermann Camilla , Herx Leonie , Gilron Ian 
Published: March 2022

Abstract
Pain is highly prevalent in patients with cancer—nearly 40% report moderate-severe pain, which is commonly treated with opioids. Increasing cancer survivorship, opioid epidemics in some regions of the world, and limited opioid access in other regions have focused attention on nonopioid treatments. Given the limitations of monotherapy, combining nonopioids—such as antiepileptics and antidepressants—have shown promise in noncancer pain. This review seeks to evaluate efficacy of nonopioid combinations for cancer-related pain. Systematic searches of PubMed, EMBASE, and Cochrane CENTRAL were conducted for double-blind, randomized, controlled trials comparing a nonopioid combination with at least one of its components and/or placebo. This search yielded 4 randomized controlled trials, published between 1998 and 2019 involving studies of (1) imipramine + diclofenac; (2) mitoxantrone + prednisone + clodronate; (3) pentoxifylline + tocopherol + clodronate; and (4) duloxetine + pregabalin + opioid. In the first 3 of these trials, trends favouring combination efficacy failed to reach statistical significance. However, in the fourth trial, duloxetine + pregabalin + opioid was superior to pregabalin + opioid. This review illustrates recognition for the need to evaluate nonopioid drug combinations in cancer pain, although few trials have been published to date. Given the growing practice of prescribing more than 1 nonopioid for cancer pain and the need to expand the evidence base for rational combination therapy, more high-quality trials in this area are needed.
NOVEL RT-qPCR ASSAYS ENABLE RAPID DETECTION AND DIFFERENTIATION BETWEEN SARS-COV-2 OMICRON (BA.1) AND BA.2 VARIANTS
Authors: Erster Oran , Kabat Areej , Asraf Hadar , Levy Virginia , Mannasse Batya , Azar Roberto , Nemet Ital , Kliker Limor , Fleishon Shay , Mandelboim Michal , Mendelson Ella , Zuckerman Neta S 
Published: March 2022

ABSTRACTIn this report, we describe the development and initial validation of novel SARS-COV-2 Omicron-specific reactions that enable the identification of Omicron (BA.1) and BA.2 variants. Mutations that are either shared by both BA.1 and BA.2, or are exclusive for BA.1 or for BA.2 were identified by bioinformatic analysis, and corresponding probe-based quantitative PCR reactions were developed to identify them. We show that multiplex combinations of these reactions provide a single-reaction identification of the sample as BA.1, BA.2, or as non-Omicron SARS-COV-2. All four reactions described herein have a sensitivity of less than ten copies per reaction, and are amendable for multiplexing. The results of this study suggest that the new assays may be useful for testing both clinical and environmental samples to differentiate between these two variants.
Identifying risk factors associated with death among patients with MDR-TB in KwaZulu-Natal, South Africa: an illustration using Weibull parametric model
Authors: Mbona Sizwe Vincent , Mwambi Henry , Chifurira Retius 
Published: March 2022

AbstractBackgroundThis study aim was to identify the risk factors associated with multidrug-resistant tuberculosis (MDR-TB) disease. The Weibull model has shown to perform better than the Cox proportional models with respect to the accuracy and efficient of the estimates. Therefore, a Weibull parametric model was employed to identify predictors of death in patients with MDR-TB and the efficiency of the models using current dataset.MethodsPatients diagnosed with MDR-TB were studied in four decentralised sites located in rural areas and one centralised hospital in KwaZulu-Natal, South Africa from July 2008 to July 2012. Patients were followed from the date of MDR-TB diagnosis until death or the last follow-up date.ResultsA total of 1 542 patients were included in the analyses: 812 and 730 from the centralised hospital and decentralised sites, respectively. Of the 1 542 enrolled, 15.9% patients died. We found that the hazard of death was significantly higher among patients treated in decentralised sites (aHR) = 1.84, 95% CI = 1.38 – 2.75; SE = 0.81 than that of those who were treated in the centralised hospital. However, the results from the Cox PH model showed an insignificant hazard of death between the decentralised sites and the centralised hospital (aHR = 1.46, 95% CI = 0.69 – 2.36; SE = 0.92). Patients who are between 31 – 40 years of age had increased hazard of death compared to those between 18 – 30 years (aHR = 1.52, 95% CI = 1.04 - 2.23). The hazard of death in female patients was 24% higher compared to male patients (aHR = 1.24, 95% CI = 0.93 - 1.63). Furthermore, patients with previous MDR-TB episodes had an increased hazard of death (aHR = 1.79, 95% CI = 0.23 – 0.62) compared to those with no previous MDR-TB episodes. The hazard of death in HIV negative patients was low compared to those who were HIV positive (aHR = 0.95, 95% CI = 0.57 – 0.77).ConclusionMore health facilities are needed especially in decentralised places and that can help the 2030 World Health Organisation strategy to reduce or end TB infection.
A gene expression map of host immune response in human brucellosis
Authors: Mitroulis Ioannis , Chrysanthopoulou Akrivi , Divolis Georgios , Ioannidis Charalampos , Ntinopoulou Maria , Tasis Athanasios , Konstantinidis Theocharis , Soteriou Natalia , Lallas George , Mitka Stella , Lesche Mathias , Dahl Andreas , Gembardt Stephanie , Panopoulou Maria , Sideras Paschalis , Wielockx Ben , Coskun Ünal , Ritis Konstantinos , Skendros Panagiotis 
Published: March 2022

ABSTRACTBrucellosis is a common zoonotic disease caused by intracellular pathogens of the genus Brucella. Brucella infects macrophages and evades clearance mechanisms, which results in chronic parasitism. Herein, we studied the molecular changes that take place in human brucellosis bothin vitroandin vivo. RNA sequencing was performed in primary human macrophages (Μφ) and polymorphonuclear neutrophils (PMNs) infected with clinical strains ofB. melitensis. We observed a downregulation in the expression of genes involved in host response, such as TNF signaling, IL-1β production and phagosome formation in Μφ, and phosphatidylinositol signaling and TNF signaling in PMNs, being in line with the ability of the pathogen to survive within phagocytes. Further transcriptomic analysis of isolated peripheral blood mononuclear cells (PBMCs) and PMNs from patients with acute brucellosis before treatment initiation and after successful treatment revealed a positive correlation of the molecular signature of active disease with pathways associated with response to interferons (IFN). We identified 24 common genes that were significantly altered in both PMNs and PBMCs, including genes involved in IFN signaling that were downregulated after treatment in both cell populations, andIL1R1that was upregulated. The levels of several inflammatory mediators were evaluated in the serum of these patients, and we observed increased levels of IFN-γ, IL-1β and IL-6 before the treatment of acute brucellosis. An independent cohort of patients with chronic brucellosis also revealed the increased levels of IFN-γ during relapse compared to remissions. Taken together, this study provides for the first time an in-depth analysis of the molecular alterations that take place in human phagocytes upon infection, and in peripheral blood immune populations during active disease.
Proteogenomics refines the molecular classification of chronic lymphocytic leukemia
Authors: Herbst Sophie A. , Vesterlund Mattias , Helmboldt Alexander J. , Jafari Rozbeh , Siavelis Ioannis , Stahl Matthias , Schitter Eva C. , Liebers Nora , Brinkmann Berit J. , Czernilofsky Felix , Roider Tobias , Bruch Peter-Martin , Iskar Murat , Kittai Adam , Huang Ying , Lu Junyan , Richter Sarah , Mermelekas Georgios , Umer Husen Muhammad , Knoll Mareike , Kolb Carolin , Lenze Angela , Cao Xiaofang , Österholm Cecilia , Wahnschaffe Linus , Herling Carmen , Scheinost Sebastian , Ganzinger Matthias , Mansouri Larry , Kriegsmann Katharina , Kriegsmann Mark , Anders Simon , Zapatka Marc , Poeta Giovanni Del , Zucchetto Antonella , Bomben Riccardo , Gattei Valter , Dreger Peter , Woyach Jennifer , Herling Marco , Müller-Tidow Carsten , Rosenquist Richard , Stilgenbauer Stephan , Zenz Thorsten , Huber Wolfgang , Tausch Eugen , Lehtiö Janne , Dietrich Sascha 
Published: March 2022

SummaryCancer heterogeneity at the proteome level may explain differences in therapy response and prognosis beyond the currently established genomic and transcriptomic based diagnostics. The relevance of proteomics for disease classifications remains to be established in clinically heterogeneous cancer entities such as chronic lymphocytic leukemia (CLL). Here, we characterized the proteome and transcriptome in-depth alongside genetic and ex-vivo drug response profiling in a clinically well annotated CLL discovery cohort (n= 68). Unsupervised clustering of the proteome data revealed six subgroups. Five of these proteomic groups were associated with genetic features, while one group was only detectable at the proteome level. This new group was characterized by accelerated disease progression, high spliceosomal protein abundances associated with aberrant splicing, and low B cell receptor signaling protein abundances (ASB-CLL). We developed classifiers to identify ASB-CLL based on its characteristic proteome or splicing signature in two independent cohorts (n= 165, n= 169) and confirmed that ASB-CLL comprises about 20 % of CLL patients. The inferior overall survival observed in ASB-CLL was independent of both TP53- and IGHV mutation status. Our multi-omics analysis refines the classification of CLL and highlights the potential of proteomics to improve cancer patient stratification beyond genetic and transcriptomic profiling.Single sentence summaryWe performed the largest proteogenomic analysis of CLL, linked proteomic profiles to clinical outcomes, and discovered a new poor outcome subgroup (ASB-CLL).
VIsoQLR: an interactive tool for the detection, quantification and fine-tuning of isoforms using long-read sequencing
Authors: Núñez-Moreno Gonzalo , Tamayo Alejandra , Ruiz-Sánchez Carolina , Cortón Marta , Mínguez Pablo 
Published: March 2022

ABSTRACTDNA variants altering the pre-mRNA splicing process represent an underestimated cause of human genetic diseases. Their association with disease traits should be confirmed using functional assays from patient cell lines or other alternative models to detect the formation of aberrant mRNAs. Long-read sequencing is a suitable technique to identify and quantify mRNA isoforms. Available isoform clusterization and/or quantification tools are generally designed for the whole transcriptome analysis. Experiments focusing on a single locus analysis need more precise data fine-tuning and visualization tools.Here we describe VIsoQLR, an interactive analyzer, viewer and editor for the semi-automated identification and quantification of known and novel isoforms using long-read sequencing data. VIsoQLR is tailored to thoroughly analyze mRNA expression and maturation in low-throughput splicing assays. This tool takes sequences aligned to a reference, defines consensus splice sites, and quantifies isoforms. Users can edit splice sites through dynamic and interactive graphics and tables as part of their manual curation. Known transcripts, or isoforms detected by other methods, can also be imported as references for comparison. Here, we explain VIsoQLR principles and features, and show its applicability in a case study example using Nanopore sequencing. VIsoQLR is available at https://github.com/TBLabFJD/VIsoQLR.
Manipulating prior beliefs causally induces under- and overconfidence
Authors: Van Marcke Hélène , Le Denmat Pierre , Verguts Tom , Desender Kobe 
Published: March 2022

AbstractMaking a decision is invariably accompanied by a sense of confidence in that decision. Across subjects and tasks, there is widespread variability in the exact level of confidence, even for tasks that do not differ in objective difficulty. Such expressions of under- and overconfidence are of vital importance, as they relate to fundamental life outcomes. Yet, a computational account specifying the mechanisms underlying under- and overconfidence is currently missing. Here, we propose that prior beliefs in the ability to perform a task, based on prior experience with this or a similar task, explain why confidence can differ dramatically across subjects and tasks, despite similar performance. In two perceptual decision-making experiments, we provide evidence for this hypothesis by showing that manipulating prior beliefs about task performance in a training phase causally influences reported levels of confidence in a test phase, while leaving objective performance in the test phase unaffected. This is true both when prior beliefs are induced via manipulated comparative feedback and via manipulating task difficulty during the training phase. We account for these results within an accumulation-to-bound model by explicitly modeling prior beliefs based on earlier exposure to the task. Decision confidence is then quantified as the probability of being correct conditional on these prior beliefs, leading to under- or overconfidence depending on the task context. Our results provide a fundamental mechanistic insight into the computations underlying under- and overconfidence in perceptual decision-making.
Molecular and cognitive signatures of ageing partially restored through synthetic delivery of IL2 to the brain
Authors: Lemaitre Pierre , Tareen Samar , Pasciuto Emanuela , Mascali Loriana , Martirosyan Araks , Callaerts-Vegh Zsuzsanna , Dooley James , Holt Matthew G. , Yshii Lidia , Liston Adrian 
Published: March 2022

AbstractCognitive decline is a common pathological outcome during aging, with an ill-defined cellular or molecular basis. Among the cellular changes observed with age are alterations to neuronal plasticity, changes in the glial compartment and the decline of the neurogenic niche. In the recent years, the concept of inflammaging, defined as a low-grade inflammation increasing with age, has emerged as a nexus for age-related diseases. This increase of basal inflammation is also observed in the central nervous system. While not classically considered a neurological cell type, infiltrating T cells increase in the brain with age, and may be responsible for amplification of inflammatory cascades and disruptions to the neurogenic niche. Recently, a small resident population of regulatory T cells has been identified in the brain, and the capacity of IL2-mediated expansion of this population to counter neuroinflammatory disease has been demonstrated. Here we test a brain-specific IL2 delivery system for the prevention of neurological decline in aging mice. We identify the molecular hallmarks of aging in the brain glial compartments, and identify partial restoration of this signature through IL2 treatment. At a behavioral level, brain IL2 delivery prevented the age-induced defect in spatial learning, without improving the general decline in motor skill or arousal. These results identify immune modulation as a potential path to preserving cognitive function for healthy ageing.
Ascorbic acid derived carbon dots promote circadian rhythm and contribute to attention deficit hyperactivity disorder
Authors: Huang Jian , Wang Yun , Zhong Zhaomin , Ma Yurong , Liu Changhong , Deng Keru , Huang Hui , Liu Yang , Ding Xin , Kang Zhenhui 
Published: March 2022

ABSTRACTAttention deficit hyperactivity disorder (ADHD) is one of the most prevalent psychiatric disorders in children, and ADHD patients always display circadian abnormalities. While, the ADHD drugs currently used in clinic have strong side effects, such as psychosis, allergic reactions and heart problems. Here, we demonstrated carbon dots derived from the ascorbic acid (VCDs) could strongly rescue the hyperactive and impulsive behaviour of a zebrafish ADHD disease model caused byper1bmutation. VCDs prolonged the circadian period of zebrafish for more than half an hour. In addition, the amplitude and circadian phase were also changed. The dopamine level was specifically increased, which may be caused by stimulation of the dopaminergic neuron development in the midbrain. Notably, it was found that the serotonin level was not altered by VCDs treatments. Also, the gene transcriptome effects of VCDs were discussed in present work. Our results provided the dynamic interactions of carbon dots with circadian system and dopamine signaling pathway, which illustrates a potential application of degradable and bio-safe VCDs for the treatment of the attention deficient and hyperactive disorder through circadian intervention.Brief summary
Optimal vaccination with time-varying based on immunity barrier in Hunan Province, China
Authors: Guo Xiaohao , Liu Ziyan , Yang Shiting , Zhao Zeyu , Guo Yichao , Abudurusuli Guzainuer , Rui Jia , Wang Yao , Zhao Shanlu , Zeng Ge , Hu Shixiong , Luo Kaiwei , Chen Tianmu 
Published: March 2022

AbstractThe current outbreak of novel coronavirus disease 2019 (COVID-19) is already causing a serious disease burden worldwide, this paper analyzed data of a delta variant Covid-19 outbreak in Hunan, China, and proposed an optimal dose-wise dynamical vaccinating process based on local contact pattern and vaccine coverage that minimize the accumulative cases in a certain future time interval. The optimized result requires an immediate vaccination to that none vaccinated at age group 30 to 39, which is coherent to the prevailing strategies. The dose-wise optimal vaccinating process can be directive for countries or regions where vaccines are not abundant. We recommend that vaccination should be further intensified to increase the coverage of booster shots, thus effectively reducing the spread of COVID-19.
Predictive Model of Risk Factors of High Flow Nasal Cannula Using Machine Learning in COVID-19
Authors: Matsunaga Nobuaki , Kamata Keisuke , Asai Yusuke , Tsuzuki Shinya , Sakamoto Yasuaki , Ijichi Shinpei , Akiyama Takayuki , Yu Jiefu , Yamada Gen , Terada Mari , Suzuki Setsuko , Suzuki Kumiko , Saito Sho , Hayakawa Kayoko , Ohmagari Norio 
Published: March 2022

AbstractBackgroundWith the rapid increase in the number of COVID-19 patients in Japan, the number of patients receiving oxygen at home has also increased rapidly, and some of these patients have died. An efficient approach to identify high-risk patients with slowly progressing and rapidly worsening COVID-19, and to avoid missing the timing of therapeutic intervention will improve patient prognosis and prevent medical complications.MethodsPatients admitted to medical institutions in Japan from November 14, 2020 to April 11, 2021 and registered in the COVID-19 Registry Japan were included. Risk factors for patients with High Flow Nasal Cannula invasive respiratory management or higher were comprehensively explored using machine learning. Age-specific cohorts were created, and severity prediction was performed for the patient surge period and normal times, respectively.ResultsWe were able to obtain a model that was able to predict severe disease with a sensitivity of 57% when the specificity was set at 90% for those aged 40-59 years, and with a specificity of 50% and 43% when the sensitivity was set at 90% for those aged 60-79 years and 80 years and older, respectively. We were able to identify lactate dehydrogenase level (LDH) as an important factor in predicting the severity of illness in all age groups.DiscussionUsing machine learning, we were able to identify risk factors with high accuracy, and predict the severity of the disease. Using machine learning, we were able to identify risk factors with high accuracy, and predict the severity of the disease. We plan to develop a tool that will be useful in determining the indications for hospitalisation for patients undergoing home care and early hospitalisation.