bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of ferroptosis‐related genes in CD8+ NKT cells and classical monocytes may affect the immunotherapy response after combined treatment in triple negative breast cancer
Authors: Liu Zheming , He Songjiang , Huang Zhou , Liu Jiahui , Gong Yiping , Yao Yi , Zhang Xue 
Published: October 2023

AbstractBackgroundDrug resistance has led to the failure of immunotherapy in triple negative breast cancer patients. Here we aimed to explore the mechanisms of drug resistance in patients in order to enhance their response to immunotherapy.MethodsWe downloaded publicly available single‐cell RNA‐sequencing data of peripheral blood mononuclear cells from patients after treatment to investigate the possible mechanisms of drug resistance. The publicly available TCGA transcriptomic data and somatic mutation data were used for further validation. In this study, a series of bioinformatics and machine learning methods were employed.ResultsWe identified the vital roles of CD8+ NKT cells and classical monocytes in the immunotherapy response of triple‐negative breast cancer patients. The proportion of these cell types was significantly increased in group partial response. We also found that downregulation of ferroptosis‐related genes regulates the immune pathway. The analysis of scRNA data and TCGA transcriptomic data presented that DUSP1 may play a crucial role in immunotherapy resistance.ConclusionOverall, the composition of the tumor microenvironment affects the immunotherapy response of patients, and DUSP1 may be a potential target for overcoming drug resistance.
Letter: Exploring the clinical utility of ammonia in critically ill patients with cirrhosis: More to do?
Authors: Dong Jia‐Jia , Zhang Qiong‐Ying , Cai Yi‐Jing 
Published: October 2023

LINKED CONTENTThis article is linked to Cardoso et al papers. To view these articles, visit https://doi.org/10.1111/apt.17650 and https://doi.org/10.1111/apt.17725
Letter: Exploring the clinical utility of ammonia in critically ill patients with cirrhosis: More to do? Authors' reply
Authors: Cardoso Filipe S. , Kim Minjee , Pereira Rui , Bagulho Luís , Fidalgo Pedro , Pawlowski Anna , Wunderink Richard , Germano Nuno , Bagshaw Sean M. , Abraldes Juan G. , Karvellas Constantine J. 
Published: October 2023

LINKED CONTENTThis article is linked to Cardoso et al papers. To view these articles, visithttps://doi.org/10.1111/apt.17650andhttps://doi.org/10.1111/apt.17698
Review: Systematic review and metasynthesis of qualitative literature on young people's experiences of going to A&E/emergency departments for mental health support
Authors: Cadorna Gianna , Vera San Juan Norha , Staples Heather , Johnson Sonia , Appleton Rebecca 
Published: October 2023

BackgroundThere has been an increase in children and young people attending emergency departments for mental health reasons, including self‐harm. Patients often report having poor experiences when attending emergency departments for mental health support. However, there has yet to be a review exploring the experiences of young people. Our aim in this study was to synthesise qualitative literature on young people's experiences of going to emergency departments for mental health support.MethodsA systematic review and metasynthesis were conducted. Five databases and grey literature were searched for relevant studies. Five articles met study criteria and were analysed using an iterative process of thematic synthesis.ResultsThe synthesis yielded four overarching themes: (a) emergency departments' inability to meet the mental health needs of young people, (b) emergency departments exacerbating patient distress, (c) patients feeling like a burden or undeserving of treatment and (d) consequences of poor emergency department experiences.ConclusionsThese findings (based on a still very limited literature) highlight the role that emergency departments have in relation to being a key point of contact with young people who self‐harm. To properly engage with patients, emergency departments need to have the resources to provide compassionate care and follow clinical guidelines regarding assessments.
Agreement between self‐reported and objectively assessed physical activity among out‐of‐hospital cardiac arrest survivors
Authors: Heimburg Katarina , Lilja Gisela , Blennow Nordström Erik , Friberg Hans , Gregersen Oestergaard Lisa , Grejs Anders M. , Keeble Thomas R. , Mion Marco , Nielsen Niklas , Rylander Christian , Segerström Magnus , Thomsen Ida Katrine , Ullén Susann , Undén Johan , Wise Matthew P. , Cronberg Tobias , Tornberg Åsa B. 
Published: October 2023

AbstractBackgroundLow level of physical activity is a risk factor for new cardiac events in out‐of‐hospital cardiac arrest (OHCA) survivors. Physical activity can be assessed by self‐reporting or objectively by accelerometery.AimTo investigate the agreement between self‐reported and objectively assessed physical activity among OHCA survivorsHypothesisSelf‐reported levels of physical activity will show moderate agreement with objectively assessed levels of physical activity.MethodCross‐sectional study including OHCA survivors in Sweden, Denmark, and the United Kingdom. Two questions about moderate and vigorous intensity physical activity during the last week were used as self‐reports. Moderate and vigorous intensity physical activity were objectively assessed with accelerometers (ActiGraph GT3X‐BT) worn upon the right hip for 7 consecutive days.ResultsForty‐nine of 106 OHCA survivors answered the two questions for self‐reporting and had 7 valid days of accelerometer assessment. More physically active days were registered by self‐report compared with accelerometery for both moderate intensity (median 5 [3:7] vs. 3 [0:5] days; p < 0.001) and vigorous intensity (1 [0:3] vs. 0 [0:0] days; p < 0.001). Correlations between self‐reported and accelerometer assessed physical activity were sufficient (moderate intensity: rs = 0.336, p = 0.018; vigorous intensity: rs = 0.375, p = 0.008), and agreements were fair and none to slight (moderate intensity: k = 0.269, p = 0.001; vigorous intensity: k = 0.148, p = 0.015). The categorization of self‐reported versus objectively assessed physical activity showed that 26% versus 65% had a low level of physical activity.ConclusionOHCA survivors reported more physically active days compared with the results of the accelerometer assessment and correlated sufficiently and agreed fairly and none to slightly.
Using repeated measures to study the contribution of alcohol consumption and smoking to the social gradient in all‐cause mortality: Results from the Stockholm Public Health Cohort
Authors: Berg Lisa , Landberg Jonas , Thern Emelie 
Published: October 2023

AbstractIntroductionThe social gradient in consumption behaviours has been suggested to partly explain health inequalities. The majority of previous studies have only included baseline measurements and not considered potential changes in behaviours over time. The study aimed to investigate the contribution of alcohol consumption and smoking to the social gradient in mortality and to assess whether the use of repeated measurements results in larger attenuations of the main association compared to using single baseline assessments.MethodsLongitudinal survey data from the population‐based Stockholm Public Health Cohort from 2006 to 2014 was linked to register data on mortality until 2018 for 13,688 individuals and analysed through Cox regression.ResultsLow socioeconomic position (SEP) was associated with increased mortality compared with high SEP; hazard ratios 1.56 (95% CI 1.30–1.88) for occupational status and 1.77 (95% CI 1.49–2.11) for education, after adjustment for demographic characteristics. Using repeated measurements, alcohol consumption and smoking explained 44% of the association between occupational status and all‐cause mortality. Comparing repeated and baseline measures, the percentage attenuation due to alcohol consumption increased from 11% to 18%, whereas it remained similar for smoking (25–23%).Discussion and ConclusionsSmoking and alcohol consumption explained a large part of the association between SEP and mortality. Comparing results from time‐fixed and time‐varying models, there was an increase in overall percentage attenuation that was mainly due to the increased proportion explained by alcohol consumption. Repeated measurements provide a better estimation of the contribution of alcohol consumption, but not smoking, for the association between SEP and mortality.
Patterns of anti‐CGRP mAbs use and variation of triptan consumption following treatment initiation: A descriptive drug utilization study in the Tuscany region, Italy
Authors: Hyeraci Giulia , Paoletti Olga , Iannone Luigi Francesco , Gini Rosa , De Cesaris Francesco , Geppetti Pierangelo , Roberto Giuseppe 
Published: October 2023

AbstractObjectiveTo describe the pattern of anti‐calcitonin gene–related peptide monoclonal antibodies (anti‐CGRP mAbs) utilization in the Tuscany region, Italy, and the variation of triptan consumption after treatment initiation.BackgroundGiven the recent commercialization of anti‐CGRP mAbs as migraine preventive medications, real‐world evidence on their patterns of utilization and their impact on migraine abortive medication use is still limited.MethodsA retrospective, descriptive, cohort study on the real‐world utilization of anti‐CGRP mAbs was performed using the population‐based regional administrative database of Tuscany. Patients with ≥1 anti‐CGRP mAb dispensing (namely erenumab, galcanezumab, fremanezumab) between April 1, 2019, and September 30, 2021, were identified. The first dispensing was the cohort entry (CE). New users (NUs) were patients with no anti‐CGRP mAb dispensing before CE. Kaplan–Meier (KM) curves were plotted to describe the cumulative probability of remaining with the initial anti‐CGRP mAb during a 15‐month follow‐up period as a measure of treatment persistence. Among NUs with ≥2 triptan dispensings during the 6 months before CE (i.e., baseline), the mean monthly number of triptan dosage units dispensed was measured in five consecutive follow‐up time windows (months 1–3, 4–6, 7–9, 10–12, 13–15) and the difference from the baseline was calculated.ResultsA total of 624 NUs (erenumab = 295, galcanezumab = 223, fremanezumab = 106) were identified, of whom 188 (78%) were women. Mean age was 49.2 years (standard deviation [SD] = 12.6). The survival to discontinuation at 6, 12, and 15 months was about 69%, 48%, and 6%, respectively. The survival to switch was about 6% at 15 months. The observed variation of triptan consumption at 3/6/9/12/15 months and the corresponding SD was −4.4 [8.2]/−5.2 [9.0]/−5.5 [9.2]/−5.4 [9.2]/−4.5 [10.0], respectively.ConclusionPatient demographics reflect the place of these medications in therapy. Overall, findings seem to indicate a favorable tolerability and effectiveness profile. Further studies are warranted to better establish the long‐term comparative effectiveness, safety, and cost effectiveness of anti‐CGRP mAbs compared to other preventive medications.
A HYBRID ANALYSIS OF THE FRENCH PRONOUN EN*
Authors: Hvidsten Eirik 
Published: October 2023

AbstractThis paper puts forward a novel account of the clitic pronoun en in French. It is shown that previous analyses cannot account for the rich nominal structure involved in en‐pronominalization, in particular structures with stranded DP‐internal remnants. The analysis proposed sees en‐pronominalization as a hybrid between pronominalization and ellipsis, which includes DP‐internal focus movement for the stranded remnants. It will be argued that en itself is best analyzed as being derived from an nP within the DP, even when it seemingly pronominalizes the entire DP. Following Cinque (2010), the analysis presented here also assumes that only modifiers of the indirect kind can be stranded by en‐pronominalization.
Residual Stresses in Surgical Growing Rods
Authors: Croonenborghs Maïté , Ismail Karim , Mousny Maryline , Delannay Laurent , Everaerts Joris , Korsunsky Alexander M. , Jacques Pascal J. , Pardoen Thomas 
Published: October 2023

Abstract
The treatment of early onset scoliosis using surgical growing rods suffers from high failure rate. Fatigue resistance can be improved by inducing compressive residual stresses within the near surface region. An in-depth investigation of the residual stresses profile evolution is performed through the sequence of material processing steps followed by surgeons handling operations, in connection to material properties. The final goal is to guide further improvements of growing rod lifetime. Residual stress evaluation was carried out on Ti-6Al-4V rods using digital image correlation applied to microbeam ring-core milling by focused ion beam. This provided experimental stress profiles in shot-peened rods before and after bending and demonstrated that compressive residual stresses are maintained at both concave and convex rod sides. A finite element model using different core and skin conditions was validated by comparison to experiments. The combination of an initial shot peening profile associated with a significant level of backstress was found to primarily control the generation of compressive stresses at the rod surface after bending. Guidelines to promote larger compressive stresses at the surface were formulated based on a parametric analysis. The analysis revealed the first order impact of the initial yield strength, kinematic hardening parameters and intensity of the shot peening operation, while the bending angle and the depth of shot peening stresses were found to be of minor importance. Materials exhibiting large kinematic hardening and low yield strength should be selected in order to induce compressive residual stresses at key fatigue initiation site.
Proteasome activity is required for reovirus entry into cells
Authors: Abad Andrew T. , McNamara Andrew J. , Danthi Pranav 
Published: October 2023

ABSTRACT
Since viruses have limited coding capacity in their genomes, they use host cell machinery to complete virtually every stage of their replication cycle. Mammalian orthoreovirus (reovirus) is comprised of two concentric protein shells, the inner core and the outer capsid. Following attachment to its receptor, reovirus enters the cell by receptor-mediated endocytosis. Within endosomes, reovirus utilizes host acid-dependent proteases to process the viral outer capsid. Specifically, the outer capsid protein σ3 is degraded, and μ1 is cleaved to form the disassembly intermediate infectious subvirion particles (ISVPs). ISVPs undergo additional conformational changes into ISVP*s that release small peptides, which mediate the penetration of endosomal membranes. Membrane penetration allows for delivery of the remaining viral core into the cytoplasm for subsequent gene expression. Here, we describe that proteasomes control an entry step of reovirus particles. We show that chemically inhibiting the proteasome blocks infection at a stage following ISVP formation but prior to transcriptional activation of cores. Specifically, inhibition of the proteasome prevents conformational changes in μ1 characteristic of ISVP-to-ISVP* conversion. In the absence of these conformational changes, cores are unable to be delivered and become transcriptionally active, thereby blocking viral replication. This work highlights a previously unknown way in which reovirus relies on host factors for successful replication.

IMPORTANCE
Due to their limited genetic capacity, viruses are reliant on multiple host systems to replicate successfully. Mammalian orthoreovirus (reovirus) is commonly used as a model system for understanding host-virus interactions. In this study, we identify that the proteasome system, which is critical for cellular protein turnover, affects reovirus entry. Inhibition of the proteasome using a chemical inhibitor blocks reovirus uncoating. Blocking these events reduces subsequent replication of the virus. This work identifies that additional host factors control reovirus entry.
Silencing essential gene expression in
Mycobacterium abscessus
during infection
Authors: Boudehen Yves-Marie , Tasrini Yara , Aguilera-Correa John Jairo , Alcaraz Matthéo , Kremer Laurent 
Published: October 2023

ABSTRACT

Mycobacterium abscessus
is a multi-drug-resistant non-tuberculous mycobacterial species causing tuberculosis-like lung infections. The functional characterization of the extensive repertoire of genes encoding virulence factors and drug targets has been largely restricted by the lack of powerful genetic tools. In this study, we evaluated the performances of a Tet-OFF system, previously optimized for
M. tuberculosis
and
M. smegmatis
. Fluorescence reporter
M. abscessus
strains were developed where mCherry was under the control of the Tet-OFF regulatory system on an integrative plasmid. The addition of anhydrotetracycline (ATc) correlated with a decrease in fluorescence intensity not only in solid and broth medium but also in colony biofilms, for both smooth and rough variants of
M. abscessus
. Next, unmarked
mmpL3
conditional knockdown mutants were engineered in both smooth and rough
M. abscessus
. Biochemical studies indicated that the addition of ATc was associated with a dose-dependent decrease in (i) the production of the MmpL3 protein, (ii) the biosynthesis of trehalose dimycolate and mycolylated arabinogalactan, (iii) bacterial viability on agar and liquid medium as well as in biofilms. Importantly, intravenous injection of ATc in zebrafish embryos infected with the rough
mmpL3
conditional mutant impeded bacterial growth and correlated with a significant gain in embryo survival. These results suggest that
mmpL3
is essential for
M. abscessus
growth
in vitro
and in the infected host, thus validating MmpL3 as an attractive drug target. Together, this study demonstrates the potential of ATc-dependent repression to modulate the expression of
M. abscessus
genes in the infected host.

IMPORTANCE

Mycobacterium abscessus
represents the most common rapidly growing mycobacterial pathogen in cystic fibrosis and is extremely difficult to eradicate. Essential genes are required for growth, often participate in pathogenesis, and encode valid drug targets for further chemotherapeutic developments. However, assessing the function of essential genes in
M. abscessus
remains challenging due to the limited spectrum of efficient genetic tools. Herein, we generated a Tet-OFF-based system allowing to knock down the expression of
mmpL3
, encoding the mycolic acid transporter in mycobacteria. Using this conditional mutant, we confirm the essentiality of
mmpL3
in planktonic cultures, in biofilms, and during infection in zebrafish embryos. Thus, in this study, we developed a robust and reliable method to silence the expression of any
M. abscessus
gene during host infection.
Role of Antimicrobial Peptides in Immunity of Parasitic Leeches
Authors: Kaygorodova I. A. 
Published: October 2023

Abstract
The review summarizes the current state of knowledge about leech immunity, with emphasis on the special role of antimicrobial peptides (AMPs), and highlights the wide variety of primary AMP structures, which seem to correlate with a variety of life strategies and the ecology of ectoparasites. Antimicrobial proteins and AMPs are a diverse class of natural molecules that are produced in all living organisms in response to an attack by a pathogen and are essential components of the immune system. AMPs can have a wide range of antibiotic activities against foreign and opportunistic bacteria, fungi, and viruses. AMPs play an important role in selection of colonizing bacterial symbionts, thus helping multicellular organisms to cope with certain environmental problems. AMPs are especially important for invertebrates, which lack an adaptive immune system. Although many AMPs are similar in physicochemical properties (a total length from 10 to 100 amino acids, a positive total charge, or a high cysteine content), their immunomodulatory activities are specific for each AMP type.
Polygenic risk score predicts risk of primary sclerosing cholangitis in inflammatory bowel disease
Authors: Wang Ming-Hsi , Friton Jessica J , Raffals Laura E , Leighton Jonathan A , Pasha Shabana F , Picco Michael F , Monroe Kelly , Nix Billy D , Newberry Rodney D , Faubion William A 
Published: October 2023

BackgroundForty distinct primary sclerosing cholangitis (PSC) genomic loci have been identified through multiancestry meta-analyses. The polygenic risk score (PRS) could serve as a promising tool to discover unique disease behaviour, like PSC, underlying inflammatory bowel disease (IBD).AimTo test whether PRS indicates PSC risk in patients with IBD.Materials and methodsMayo Clinic and Washington University at St Louis IBD cohorts were used to test our hypothesis. PRS was modelled through the published PSC loci and weighted with their corresponding effect size. Logistic regression was applied to predict the PSC risk.ResultsIn total, 63 (5.6%) among 1130 patients with IBD of European ancestry had PSC. Among 381 ulcerative colitis (UC), 12% had PSC; in contrast to 1.4% in 761 Crohn disease (CD). Compared with IBD alone, IBD-PSC had significantly higher PRS (PSC risk: 3.0% at the lowest PRS quartile vs 7.2% at the highest PRS quartile, Ptrend=.03). In IBD subphenotypes subgroup analysis, multivariate analysis shows that UC-PSC is associated with more extensive UC disease (OR, 5.60; p=0.002) and younger age at diagnosis (p=0.02). In CD, multivariate analysis suggests that CD-PSC is associated with colorectal cancer (OR, 50; p=0.005).ConclusionsWe found evidence that patients with IBD with PSC presented with a clinical course difference from that of patients with IBD alone. PRS can influence PSC risk in patients with IBD. Once validated in an independent cohort, this may help identify patients with the highest likelihood of developing PSC.