bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene expression-based biomarkers designating glioblastomas resistant to multiple treatment strategies
Authors: Menyhárt Otília , Fekete János Tibor , Győrffy Balázs 
Published: March 2021

Abstract
Despite advances in molecular characterization of glioblastoma multiforme (GBM), only a handful of predictive biomarkers exist with limited clinical relevance. We aimed to identify differentially expressed genes in tumor samples collected at surgery associated with response to subsequent treatment, including temozolomide (TMZ) and nitrosoureas. Gene expression was collected from multiple independent datasets. Patients were categorized as responders/nonresponders based on their survival status at 16 months postsurgery. For each gene, the expression was compared between responders and nonresponders with a Mann–Whitney U-test and receiver operating characteristic. The package ‘roc’ was used to calculate the area under the curve (AUC). The integrated database comprises 454 GBM patients from 3 independent datasets and 10 103 genes. The highest proportion of responders (68%) were among patients treated with TMZ combined with nitrosoureas, where FCGR2B upregulation provided the strongest predictive value (AUC = 0.72, P &lt; 0.001). Elevated expression of CSTA and MRPS17 was associated with a lack of response to multiple treatment strategies. DLL3 upregulation was present in subsequent responders to any treatment combination containing TMZ. Three genes (PLSCR1, MX1 and MDM2) upregulated both in the younger cohort and in patients expressing low MGMT delineate a subset of patients with worse prognosis within a population generally associated with a favorable outcome. The identified transcriptomic changes provide biomarkers of responsiveness, offer avenues for preclinical studies and may enhance future GBM patient stratifications. The described methodology provides a reliable pipeline for the initial testing of potential biomarker candidates for future validation studies.
Second-generation laser balloon ablation for the treatment of atrial fibrillation assessed by continuous rhythm monitoring: the LIGHT-AF study
Authors: Rovaris Giovanni , Ciconte Giuseppe , Schiavone Marco , Mitacchione Gianfranco , Gasperetti Alessio , Piazzi Elena , Negro Gabriele , Montemerlo Elisabetta , Rondine Roberto , Pozzi Mattia , Casiraghi Mirko , De Ceglia Sergio , Giacopelli Daniele , Viecca Maurizio , Vicedomini Gabriele , Forleo Giovanni B , Pappone Carlo 
Published: March 2021

Abstract

Aims
Balloon-based technologies have been developed to simplify catheter ablation of atrial fibrillation (AF), to improve the clinical outcome of the procedure and to achieve durable pulmonary vein isolation (PVI). The objective of this study is to evaluate the safety and efficacy of second-generation laser balloon (LB2) ablation in the treatment of AF using a continuous cardiac rhythm monitoring strategy. Atrial tachyarrhythmias (ATas) recurrences were assessed with implantable cardiac monitors (ICMs) or devices.

Methods and results
All patients underwent LB2 ablation procedure. The primary endpoint was the first recurrence of any, &gt;5.5 and &gt;24 h duration ATas after the blanking period (90 days). In-hospital visits were performed at 3, 6, and 12 months. Seventy-three patients (68% male, mean age 59.8 ± 11.3) were included in the study. The average procedure, fluoroscopy, and laser ablation times were 81.5 ± 30.1, 21.5 ± 12.4, and 33.8 ± 9.7, respectively. All PVs were isolated using the LB2 with no need of touch-up using focal catheters. No major complications occurred during or after the procedures. The one-year freedom from recurrences was 66.9% (95% CI: 57.0–76.7%), 81.0% (69.5–88.5%), and 86.8% (76.1–92.9%) considering any, 5.5-h and 24-h cut-off duration, respectively. At 3, 6, and 12 months, any ATas was recorded in 22%, 32%, and 25% of patients, with a ≥5% arrhythmic burden documented in 4%, 5%, and 3%, respectively. Few patients reported AF-related symptoms (7%, 8%, and 5%).

Conclusion
LB2 ablation is a safe and effective procedure, showing a high freedom from recurrences and low arrhythmic burden as documented by a continuous rhythm monitoring strategy.
Local search or beyond? The influence of interfirm technological distance on co-innovation success
Authors: Huo Dong 
Published: March 2021

AbstractIn the interfirm co-innovation process, knowledge search spanning organizational boundaries is believed to be essential to innovation but is often technologically, geographically, and socially bounded. Given that spanning any type of boundary may lead to both decreased learning and increased creativity, its influence on co-innovation success remains unclear. Using a sample of 18,575 US utility patents co-invented by 6,595 dyads of firms during 1993–2002, the net effect of interfirm technological distance (which depicts cognitive boundary-spanning search) on the quality of a co-invented patent is found to depend largely on other types of boundary-spanning searches, such as cross-regional and cross-network partnerships. The net effect is negative when co-inventing partners are within the same region and network, whereas the net effect becomes positive when partners originate from distinct regions and networks. The findings advance the understanding of boundary-spanning searches of various types and their complicated interactions, suggesting that boundary spanning is crucial to co-innovation success.
Longitudinal Analysis of Human Memory T-Cell Response According to the Severity of Illness up to 8 Months After Severe Acute Respiratory Syndrome Coronavirus 2 Infection
Authors: Kang Chang Kyung , Kim Minji , Lee Soojin , Kim Gwanghun , Choe Pyoeng Gyun , Park Wan Beom , Kim Nam Joong , Lee Chang-Han , Kim Ik Soo , Jung Keehoon , Lee Dong-Sup , Shin Hyun Mu , Kim Hang-Rae , Oh Myoung-don 
Published: March 2021

Abstract

Background
Understanding the memory T-cell response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial for assessing the longevity of protective immunity after SARS-CoV-2 infection or coronavirus disease 2019 (COVID-19) vaccination. However, the longitudinal memory T-cell response up to 8 months post–symptom onset (PSO) according to the severity of illness is unknown.

Methods
We analyzed peripheral blood mononuclear cells (PBMCs) from healthy volunteers or patients with COVID-19 who experienced asymptomatic, mild, or severe illness at 2, 5, and 8 months PSO. SARS-CoV-2 spike, nucleocapsid, and membrane protein-stimulated PBMCs were subjected to flow cytometry analysis.

Results
A total of 24 patients (7 asymptomatic, 9 with mild disease, and 8 with severe disease) and 6 healthy volunteers were analyzed. SARS-CoV-2–specific OX40+CD137+CD4+ T cells and CD69+CD137+CD8+ T cells persisted at 8 months PSO. Also, antigen-specific cytokine-producing or polyfunctional CD4+ T cells were maintained for up to 8 months PSO. Memory CD4+ T-cell responses tended to be greater in patients who had severe illness than in those with mild or asymptomatic disease.

Conclusions
Memory response to SARS-CoV-2, based on the frequency and functionality, persists for 8 months PSO. Further investigations involving its longevity and protective effect from reinfection are warranted.
Feather Gene Expression Elucidates the Developmental Basis of Plumage Iridescence in African Starlings
Authors: Rubenstein Dustin R , Corvelo André , MacManes Matthew D , Maia Rafael , Narzisi Giuseppe , Rousaki Anastasia , Vandenabeele Peter , Shawkey Matthew D , Solomon Joseph 
Published: March 2021

Abstract
Iridescence is widespread in the living world, occurring in organisms as diverse as bacteria, plants, and animals. Yet, compared to pigment-based forms of coloration, we know surprisingly little about the developmental and molecular bases of the structural colors that give rise to iridescence. Birds display a rich diversity of iridescent structural colors that are produced in feathers by the arrangement of melanin-containing organelles called melanosomes into nanoscale configurations, but how these often unusually shaped melanosomes form, or how they are arranged into highly organized nanostructures, remains largely unknown. Here, we use functional genomics to explore the developmental basis of iridescent plumage using superb starlings (Lamprotornis superbus), which produce both iridescent blue and non-iridescent red feathers. Through morphological and chemical analyses, we confirm that hollow, flattened melanosomes in iridescent feathers are eumelanin-based, whereas melanosomes in non-iridescent feathers are solid and amorphous, suggesting that high pheomelanin content underlies red coloration. Intriguingly, the nanoscale arrangement of melanosomes within the barbules was surprisingly similar between feather types. After creating a new genome assembly, we use transcriptomics to show that non-iridescent feather development is associated with genes related to pigmentation, metabolism, and mitochondrial function, suggesting non-iridescent feathers are more energetically expensive to produce than iridescent feathers. However, iridescent feather development is associated with genes related to structural and cellular organization, suggesting that, while nanostructures themselves may passively assemble, barbules and melanosomes may require active organization to give them their shape. Together, our analyses suggest that iridescent feathers form through a combination of passive self-assembly and active processes.
Constituent order in silent gesture reflects the perspective of the producer
Authors: Kirton Fiona , Kirby Simon , Smith Kenny , Culbertson Jennifer , Schouwstra Marieke 
Published: March 2021

Abstract
Understanding the relationship between human cognition and linguistic structure is a central theme in language evolution research. Numerous studies have investigated this question using the silent gesture paradigm in which participants describe events using only gesture and no speech. Research using this paradigm has found that Agent–Patient–Action (APV) is the most commonly produced gesture order, regardless of the producer’s native language. However, studies have uncovered a range of factors that influence ordering preferences. One such factor is salience, which has been suggested as a key determiner of word order. Specifically, humans, who are typically agents, are more salient than inanimate objects, so tend to be mentioned first. In this study, we investigated the role of salience in more detail and asked whether manipulating the salience of a human agent would modulate the tendency to express humans before objects. We found, first, that APV was less common than expected based on previous literature. Secondly, salience influenced the relative ordering of the patient and action, but not the agent and patient. For events involving a non-salient agent, participants typically expressed the patient before the action and vice versa for salient agents. Thirdly, participants typically omitted non-salient agents from their descriptions. We present details of a novel computational solution that infers the orders participants would have produced had they expressed all three constituents on every trial. Our analysis showed that events involving salient agents tended to elicit AVP; those involving a non-salient agent were typically described with APV, modulated by a strong tendency to omit the agent. We argue that these findings provide evidence that the effect of salience is realized through its effect on the perspective from which a producer frames an event.
Lower Limb Biomechanical Responses During a Standardized Load Carriage Task are Sex Specific
Authors: Wills Jodie A , Saxby David J , Lenton Gavin K , Doyle Timothy L A 
Published: March 2021

ABSTRACT

Introduction
The purpose of this study was to investigate sex-specific lower limb biomechanical adaptations during a standardized load carriage task in response to a targeted physical training program.

Materials and Methods
Twenty-five healthy civilians (males [n = 13] and females [n = 12]) completed a load carriage task (5 km at 5.5 km·h−1, wearing a 23 kg vest) before and after a 10-week lower-body–focused training program. Kinematics and ground reaction force data were collected during the task and were used to estimate lower limb joint kinematics and kinetics (i.e., moments and powers). Direct statistical comparisons were not conducted due to different data collection protocols between sexes. A two-way repeated measures ANOVA tested for significant interactions between, and main effects of training and distance marched for male and female data, respectively.

Results
Primary kinematic and kinetic changes were observed at the knee and ankle joints for males and at the hip and knee joints for females. Knee joint moments increased for both sexes over the 5 km distance marched (P &gt; .05), with males demonstrating significant reductions in peak knee joint extension after training. Hip adduction, internal rotation, and knee internal rotation angles significantly increased after the 5 km load carriage task for females but not males.

Conclusion
Differences in adaptive gait strategies between sexes indicate that physical training needs to be tailored to sex-specific requirements to meet standardized load carriage task demands. The findings highlighted previously unfound sex-specific responses that could inform military training and facilitate the integration of female soldiers into physically demanding military roles.
Review of Military Casualties in Modern Conflicts—The Re-emergence of Casualties From Armored Warfare
Authors: Khorram-Manesh Amir , Goniewicz Krzysztof , Burkle Frederick M , Robinson Yohan 
Published: March 2021

ABSTRACTIntroductionThe re-emergence of armored warfare in modern conflicts has resulted in a higher number of extremity injuries, burns, and brain injuries. Despite this dramatic increase, little is reported on the type of injuries caused and their management. This review summarizes the publicly available literature and reports on the rate and type of injuries related to armored warfare, their medical outcomes, and management limitations.Materials and MethodsThis rapid evidence review involves a systematic literature search, followed by a non-systematic literature review. The reason for choosing this approach was the inherent lack of quantitative outcome data in the literature to satisfy the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. The study also used content analysis to study all peer-reviewed articles, focusing on similarities and differences in the findings necessary to formulate tentative results. The electronic search included PubMed, Scopus, and Web of Science, using the following search string: “Armored; Injuries; Mechanized; Morbidity; Mortality; War; Warfare”, alone or in combination.ResultsModern conflicts are associated with higher number of extremity injuries, burns, and brain injuries among military casualties. Several publications claim that the characteristics of armored warfare and anticipated injuries in this type of warfare might require the far forward deployment of medical support supported by a reliable casualty evacuation chain. Still the quality of the available casualty data is low.ConclusionsBecause of the limited availability of reliable data or military trauma registries, up-to-date military casualty estimation remains a recognized knowledge gap, which needs to be addressed by armed forces worldwide. The future management of modern war casualties requires professional and well-trained staff in all levels, indicating a need for educational initiatives to provide both nurses and medics a greater proportion of medical care and management capabilities and responsibilities than in past conflicts.
Coevolution of ribosomal RNA expansion segment 7L and assembly factor Noc2p specializes the ribosome biogenesis pathway between Saccharomyces cerevisiae and Candida albicans
Authors: Wang Xiangxiang , Yue Zhiyong , Xu Feifei , Wang Sufang , Hu Xin , Dai Junbiao , Zhao Guanghou 
Published: March 2021

Abstract
Ribosomes of different species share an evolutionarily conserved core, exhibiting flexible shells formed partially by the addition of species-specific ribosomal RNAs (rRNAs) with largely unexplored functions. In this study, we showed that by swapping the Saccharomyces cerevisiae 25S rRNA genes with non-S. cerevisiae homologs, species-specific rRNA variations caused moderate to severe pre-rRNA processing defects. Specifically, rRNA substitution by the Candida albicans caused severe growth defects and deficient pre-rRNA processing. We observed that such defects could be attributed primarily to variations in expansion segment 7L (ES7L) and could be restored by an assembly factor Noc2p mutant (Noc2p-K384R). We showed that swapping ES7L attenuated the incorporation of Noc2p and other proteins (Erb1p, Rrp1p, Rpl6p and Rpl7p) into pre-ribosomes, and this effect could be compensated for by Noc2p-K384R. Furthermore, replacement of Noc2p with ortholog from C. albicans could also enhance the incorporation of Noc2p and the above proteins into pre-ribosomes and consequently restore normal growth. Taken together, our findings help to elucidate the roles played by the species-specific rRNA variations in ribosomal biogenesis and further provide evidence that coevolution of rRNA expansion segments and cognate assembly factors specialized the ribosome biogenesis pathway, providing further insights into the function and evolution of ribosome.
Clinical Effectiveness and Safety of Antivirals for Influenza in Pregnancy
Authors: Chow Eric J , Beigi Richard H , Riley Laura E , Uyeki Timothy M 
Published: March 2021

Abstract
Seasonal influenza epidemics result in substantial health care burden annually. Early initiation of antiviral treatment of influenza has been shown to reduce the risk of complications and duration of illness. Pregnant and postpartum women may be at increased risk for influenza-associated complications; however, pregnant women have been generally excluded from clinical trials of antiviral treatment of influenza. In this review, we summarize the available evidence on the clinical effectiveness and safety of antiviral treatment of pregnant women with influenza. Observational data show a reduction of severe outcomes when pregnant and postpartum women are treated with oseltamivir and other neuraminidase inhibitors without increased risk of adverse maternal, fetal, or neonatal outcomes. Due to lack of safety and efficacy data for baloxavir treatment of pregnant and postpartum women, baloxavir is currently not recommended for use in these populations.
Navigating the complex realm of drug access in paediatric care
Authors: Dean Paige H , Carr Roxane , Jensen Chris , Strahlendorf Caron 
Published: March 2021

Abstract
A Drug Access Navigator (DAN) is a role that has been established in patient care settings with the goal of expediting the process by which patients obtain drugs through the Health Canada Special Access Program (SAP), individual drug companies’ patient access programs (PAP), and public and private drug plans. In the paediatric setting, the process of accessing many drugs has grown increasingly complex. The majority of paediatric prescriptions involve ‘off-label’ drug use. This leads to an increased need for drug access through the SAP and/or PAPs and demonstrates that the need for a DAN may be particularly prominent in the paediatric population. To our knowledge, there is no evidence in the literature of a DAN functioning in a paediatric setting, though there is a demonstrable need. We plan to address this need by introducing a DAN for shared use at BC Children’s Hospital, a paediatric tertiary care centre.
The effects of disease activity on neuronal and behavioural cognitive processes in systemic lupus erythematosus
Authors: Barraclough Michelle , McKie Shane , Parker Ben , Elliott Rebecca , Bruce Ian N 
Published: March 2021

Abstract

Objectives
Factors common across many chronic diseases, such as fatigue and depression affect cognitive dysfunction (CD) but the effect of SLE disease activity on CD remains unclear. We aimed to explore the effects of disease activity in SLE on cognitive function whilst taking into consideration other potential mediators.

Methods
Two groups of SLE patients were recruited; stable/low disease activity (SLE-S, n = 36) and active disease (SLE-F, n = 26). The SLE-F group were studied during a flare; with a second visit when disease activity had reduced. In addition to demographic, clinical and psychiatric data, CD was measured using a computerised battery of tests (CANTAB®). Functional MRI (fMRI) was used to examine neuronal responses to working memory and emotional processing tasks.

Results
No differences between the groups/visits were found using the CANTAB® battery. The fMRI results showed that the SLE-F group had a less attenuated response in the medial prefrontal cortex (a default mode network—DMN region) compared with the SLE-S group during the working memory task (P =0.012). Exploratory correlations within the SLE-F group showed associations between neuronal responses and depression, cognitive fatigue, disease activity measures and IL-6.

Conclusion
Functional brain processes but not cognitive behavioural measures were affected by disease activity. Flaring SLE patients were less able to suppress DMN regions during a working memory task. This could reflect emotional interference during cognitive tasks and may cause cognitive fatigue. A number of factors are associated with brain function in flaring patients, which has potential implications for holistic treatments.
IL-23 orchestrating immune cell activation in arthritis
Authors: Najm Aurélie , McInnes Iain B 
Published: March 2021

Abstract
IL-23 is a cytokine member of the IL-12 superfamily. These heterodimeric cytokines offer broad immune regulatory activity with potential effector function in inflammatory arthritis. IL-23 is a pro-inflammatory cytokine secreted by dendritic cells and macrophages. It plays a key role in both innate and adaptive immunity. By promoting and maintaining T cell differentiation into Th17 T cells, IL-23 is a key player in the pathogenesis of rheumatic diseases. Data from pre-clinical IL-23 knockout models show the major importance of IL-23 in development of arthritis. The induction and maintenance of type 17 cells, which secrete IL-17A and other pro-inflammatory cytokines, contributes to local synovial inflammation and skin inflammation in PsA, and perhaps in RA. Commensurate with this, therapeutic strategies targeting IL-23 have proven efficient in PsA in several studies, albeit not yet in RA.