bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral immunization with
Shigella sonnei
WRSs2 and WRSs3 vaccine strains elicits systemic and mucosal antibodies with functional anti-microbial activity
Authors: Shrivastava Shikha , Agnememel Alain B. , Ndungo Esther , Islam Dilara , Liang Yuanyuan , Frenck Robert W. , Pasetti Marcela F. 
Published: December 2023

ABSTRACT

Shigella
causes bacillary dysentery and is responsible for a high burden of disease globally. Several studies have emphasized the value of functional antibody activity to understand
Shigella
immunity and correlates of protection. The anti-microbial function of local (mucosal) antibodies and their contribution to preventing
Shigella
infection remain unknown. The goal of this study was to identify the functional humoral immune effectors elicited by two
Shigella sonnei
live oral vaccine candidates, WRSs2 and WRSs3. Complement-dependent bactericidal [serum bactericidal antibody (SBA)/bactericidal antibody (BA)] and opsonophagocytic killing antibody (OPKA) activity were determined in sera and stool extracts as indicators of systemic and local anti-microbial immunity. High levels of SBA/BA and OPKA were detected in serum as well as in fecal extracts from volunteers who received a single dose of WRSs2 and WRSs3. Functional antibody activity peaked on days 10 and 14 post-vaccination in fecal and serum samples, respectively. Bactericidal and OPKA titers were closely associated. Peak fold rises in functional antibody titers in serum and fecal extracts were also associated. Antibody activity interrogated in IgG and IgA purified from stool fractions identified IgG as the primary driver of mucosal bactericidal and OPKA activity, with minimal functional activity of IgA alone, highlighting an underappreciated role for IgG in bacterial clearance in the mucosa. The combination of IgG and IgA in equal proportions enhanced bactericidal and OPKA titers hinting at a co-operative or synergistic action. Our findings provide insight into the functional anti-microbial capacity of vaccine-induced mucosal IgG and IgA and propose an operative local humoral effector of protective immunity.

IMPORTANCE

There is an urgent need for a safe, effective, and affordable vaccine against
Shigella
. Understanding the immunological underpinning of
Shigella
infection and the make-up of protective immunity is critical to achieve the best approach to prevent illness caused by this mucosal pathogen. We measured the complement-dependent bactericidal and opsonophagocytic antibody killing in serum and stool extracts from adult volunteers vaccinated with
Shigella sonnei
live oral vaccine candidates WRSs2 and WRSs3. For the first time, we detected functional antibody responses in stool samples that were correlated with those in sera. Using purified stool IgA and IgG fractions, we found that functional activity was mediated by IgG, with some help from IgA. These findings provide insight into the functional anti-microbial capacity of vaccine-induced mucosal IgG and IgA and support future studies to identify potential markers of protective mucosal immunity.
Phenotypes of a
Pseudomonas aeruginosa
hypermutator lineage that emerged during prolonged mechanical ventilation in a patient without cystic fibrosis
Authors: Nozick Sophia H. , Ozer Egon A. , Medernach Rachel , Kochan Travis J. , Kumar Rebecca , Mills Jori O. , Wunderlink Richard G. , Qi Chao , Hauser Alan R. 
Published: December 2023

ABSTRACT

Hypermutator lineages of
Pseudomonas aeruginosa
arise frequently during the years of airway infection experienced by patients with cystic fibrosis and bronchiectasis but are rare in the absence of chronic infection and structural lung disease. Since the onset of the COVID-19 pandemic, large numbers of patients have remained mechanically ventilated for extended periods of time. These patients are prone to acquire bacterial pathogens that persist for many weeks and have the opportunity to evolve within the pulmonary environment. However, little is known about what types of adaptations occur in these bacteria and whether these adaptations mimic those observed in chronic infections. We describe a COVID-19 patient with a secondary
P. aeruginosa
lung infection in whom the causative bacterium persisted for >50 days. Over the course of this infection, a hypermutator lineage of
P. aeruginosa
emerged and co-existed with a non-hypermutator lineage. Compared to the parental lineage, the hypermutator lineage evolved to be less cytotoxic and less virulent. Genomic analyses of the hypermutator lineage identified numerous mutations, including in the mismatch repair gene
mutL
and other genes frequently mutated in individuals with cystic fibrosis. Together, these findings demonstrate that hypermutator lineages can emerge when
P. aeruginosa
persists following acute infections such as ventilator-associated pneumonia and that these lineages have the potential to affect patient outcomes.

IMPORTANCE

Pseudomonas aeruginosa
may evolve to accumulate large numbers of mutations in the context of chronic infections such as those that occur in individuals with cystic fibrosis. However, these “hypermutator” lineages are rare following acute infections. Here, we describe a non-cystic fibrosis patient with COVID-19 pneumonia who remained mechanically ventilated for months. The patient became infected with a strain of
P. aeruginosa
that evolved to become a hypermutator. We demonstrate that hypermutation led to changes in cytotoxicity and virulence. These findings are important because they demonstrate that
P. aeruginosa
hypermutators can emerge following acute infections and that they have the potential to affect patient outcomes in this setting.
Dietary habits in adolescent male and female handball players: the Swedish Handball Cohort
Authors: Onell Clara , Skillgate Eva , Melin Anna , Källberg Henrik , Waldén Markus , Edlund Klara , Hägglund Martin , Côté Pierre , Asker Martin 
Published: December 2023

ObjectivesThis cross-sectional study aimed to describe dietary habits in Swedish adolescent handball players and differences with respect to sex and school grade.MethodsParticipants in the Swedish Handball Cohort answered a web-survey assessing adherence to sports nutrition recommendations for meal frequency and meal timing, and the Nordic Nutrition Recommendations (NNR) for fruits/vegetables and fish/seafood, food exclusions and use of dietary supplements. Differences with respect to sex and school grade were estimated with generalised linear models, generating prevalence ratios (PR) with 95% CIs.ResultsA total of 1040 participants (16.6±0.9 years, 51% males) were included. Overall, 70% and 90%, respectively, met recommendations for meal frequency and meal timing, whereas adherence to recommended carbohydrate intake during training/game was met by 17%. Adherence to the NNR for fruits/vegetables and fish/seafood was met by 16% and 37%, respectively. Twenty-eight per cent reported using dietary supplements. Females reported lower frequency of meals, especially morning snacks (−0.6 days/week (95% CI −0.3 to −0.9)) and evening snacks (−0.8 days/week (95% CI −0.5 to –1.1)), higher prevalence of exclusions due to intolerances (PR 1.66 (95% CI 1.31 to 2.01)) and other reasons (PR 1.36 (95% CI 1.08 to 1.64)), higher adherence to the NNR for fruits/vegetables (PR 2.30 (95% CI 1.98 to 2.62)) and use of micronutrient supplements (PR 1.72 (95% CI 1.43 to 2.00)) compared with males. Only small differences were observed between school grades.ConclusionsSwedish adolescent handball players’ dietary habits are fairly in accordance with sports nutrition recommendations but not the NNR. Females appear to display more restrictive habits than males.
Women have less progression of paroxysmal atrial fibrillation: data from the RACE V study
Authors: Mulder Bart A , Khalilian Ekrami Neda , Van De Lande Martijn E , Nguyen Bao-Oanh , Weberndorfer Vanessa , Crijns Harry J , Geelhoed Bastiaan , Blaauw Yuri , Hemels Martin EW , Tieleman Robert G , Scheerder Coert OS , De Melis Mirko , Schotten Ulrich , Linz Dominik , Van Gelder Isabelle C , Rienstra Michiel 
Published: December 2023

BackgroundSex differences in atrial fibrillation (AF) are observed in terms of comorbidities, symptoms, therapies received, AF progression and cardiovascular complications.MethodsWe assessed the differences in prevalence and the determinants of AF progression, as well as the clinical characteristics and quality of life (QoL), between women and men with paroxysmal AF included in the RACE V (Reappraisal of Atrial Fibrillation: Interaction between hyperCoagulability, Electrical remodeling, and Vascular Destabilisation in the Progression of AF) study. At baseline, extensive phenotyping was done. To assess AF progression, implantable loop recorder (ILR) monitoring was used throughout follow-up. AF progression was defined as (1) progression to persistent or permanent AF or (2) progression of paroxysmal AF (>3% burden increase).Results417 patients were included, 179 (43%) of whom were women. Women were older (median 67 years vs 63 years, p<0.001), less often had coronary artery disease (n=11 (6%) vs n=36 (16%), p=0.003), had more obesity (n=57 (32%) vs n=50 (21%), p=0.013), had less epicardial and pericardial fat (median 144 (interquartile range [IQR] 94–191) mL vs 199 (IQR 146–248) mL, p<0.001; and median 89 (ICQ 61–121) mL vs 105 (IQR 83–133) mL, p<0.001, respectively) and had more impaired left atrial function. The median follow-up was 2.2 (1.6–2.8) years. 51 of 417 patients (5.5% per year) showed AF progression (15/179 (8.4%) women and 36/238 (15.1%) men, p=0.032). Multivariable analysis showed tissue factor pathway inhibitor, N-terminal prohormone brain natriuretic peptide (NT-proBNP) and PR interval being associated with AF progression in women and factor XIIa:C1 esterase, NT-proBNP and proprotein convertase subtilisin/kexin type 9 in men. QoL was not different between sexes.ConclusionDespite older age, the incidence of AF progression was lower in women. Parameters associated with AF progression varied in part between sexes, suggesting different underlying pathophysiological mechanisms.
A Composite Decision Rule of CD8+ T-cell Density in Tumor Biopsies Predicts Efficacy in Early-stage, Immunotherapy Trials
Authors: Dejardin David , Kraxner Anton , Blank Annika , Rieder Natascha , Teichgräber Volker , Städler Nicolas , Beyer Ulrich , Gomes Bruno , Charo Jehad 
Published: December 2023

Abstract

Purpose:
To examine whether CD8+ T-cell numbers in paired tumor biopsies in early-stage clinical trials can be used as an early indicator of clinical benefit for cancer immunotherapies.

Experimental Design:
Paraffin sections of tumor biopsies were stained immunohistochemically for CD8+ T cells, which were digitally enumerated. The tumor biopsies were from cancer patients in early-phase trials testing novel immunotherapeutic agents. Paired biopsies taken before the start of treatment and on-treatment were compared. A total of 155 patients were used as the training set and an additional 221 patients were used as the validation set.

Results:
Using the Cox proportional hazard model, a ≥0.9- increase in fold change (FC) on a ln scale in CD8+ T cells (corresponding to a 2.5-fold increase on the linear scale), from baseline, demonstrated a greater association with prolonged progression-free survival and allowed improved differentiation between groups above and below the threshold. Similarly, a ≥6.2 threshold in geometric mean of the on-treatment density (OTD) of T cells, which approximately corresponds to 500 cells/mm2, correlated with longer PFS. The combination of both criteria (FC and OTD) provided the best discrimination between clinically nonactive and active compounds.

Conclusions:
We propose that a composite score of CD8+ T-cell density in paired biopsies taken before and on-treatment may be a new biomarker to inform on clinical outcomes in early immunotherapy clinical trials.
Finding Fairness: Two Perspectives in International Criminal Law
Authors: Coleman Michelle 
Published: December 2023

Abstract
This review essay discusses two books: Fairness and Rights in International Criminal Procedure by Sophie Rigney and Punishing Atrocities through a Fair Trial by Jonathan Hafetz. It discusses the methods used in each book, their conceptions of fairness, and what they see as the future of fairness in international criminal law. The review argues that when the two books are read together they show how far fairness has come, where it is now, and where fairness is headed in the future.
On-Orbit Response Characteristics of Fengyun-4A Lightning Mapping Imager (LMI) and Their Impacts on LMI Detection
Authors: Hui Wen , Zhang Wenjuan , Lyu Weitao , Zhang Yijun , Li Pengfei 
Published: December 2023

Abstract
The effects of the response characteristics of the Fengyun-4A Lightning Mapping Imager (LMI) on its detection capability were studied using the raw event data of LMI in 2020. The simultaneous observation data of the Lightning Imaging Sensor (LIS) on the International Space Station (ISS) were used to evaluate the LMI detection capability. The results reveal that the minimum detectable radiance of lightning events in the 16 subregions of LMI has shown regional differences, with the southern subregions lower than the northern subregions, indicating that the southern ones are more conducive to the identification of events. The diurnal variation of the detectable event radiance in all subregions presents the main peak around noon, which comes from the influence of the bright background and varies largely in different subregions depending on the subregions’ response capability. The overall high values and regional differences of flash properties observed by LMI also show strong correlation with the variation of the minimum detectable radiance of events. Moreover, it is found that the southwest subregions have the highest coincidence ratio (CR) with ISS LIS, followed by the southeast subregions and the northeast subregions, and the northwest subregions have the lowest CR, which is closely related to the response of each subregion. The LIS flashes that can be detected by LMI are brighter, larger, and last longer compared to the total LIS flashes. The findings in this study will help explain the inconsistency of the LMI detection capability and promote the LMI data processing associated with pixel energy distribution.

Significance Statement
The Fengyun-4A (FY-4A) Lightning Mapping Imager (LMI) is the first geostationary satellite-borne lightning imager developed in China, which has the ability to continuously observe lightning within a large field of view. However, in the application of the data, it was found that the detection capability of the LMI differed significantly in different regions and exhibited diurnal variations, which may be related to the response characteristics of the LMI detector. This study reveals the effect of the response characteristics of the LMI detector on its detection results. The findings will help improve the usability of LMI data and improve the processing of these data to adjust the observation inconsistency.
PWSC: a novel clustering method based on polynomial weight-adjusted sparse clustering for sparse biomedical data and its application in cancer subtyping
Authors: Zhang Xiaomeng , Zhang Hongtao , Wang Zhihao , Ma Xiaofei , Luo Jiancheng , Zhu Yingying 
Published: December 2023

Abstract
Background
Clustering analysis is widely used to interpret biomedical data and uncover new knowledge and patterns. However, conventional clustering methods are not effective when dealing with sparse biomedical data. To overcome this limitation, we propose a hierarchical clustering method called polynomial weight-adjusted sparse clustering (PWSC).

Results
The PWSC algorithm adjusts feature weights using a polynomial function, redefines the distances between samples, and performs hierarchical clustering analysis based on these adjusted distances. Additionally, we incorporate a consensus clustering approach to determine the optimal number of classifications. This consensus approach utilizes relative change in the cumulative distribution function to identify the best number of clusters, resulting in more stable clustering results. Leveraging the PWSC algorithm, we successfully classified a cohort of gastric cancer patients, enabling categorization of patients carrying different types of altered genes. Further evaluation using Entropy showed a significant improvement (p = 2.905e−05), while using the Calinski–Harabasz index demonstrates a remarkable 100% improvement in the quality of the best classification compared to conventional algorithms. Similarly, significantly increased entropy (p = 0.0336) and comparable CHI, were observed when classifying another colorectal cancer cohort with microbial abundance. The above attempts in cancer subtyping demonstrate that PWSC is highly applicable to different types of biomedical data. To facilitate its application, we have developed a user-friendly tool that implements the PWSC algorithm, which canbe accessed at http://pwsc.aiyimed.com/.

Conclusions
PWSC addresses the limitations of conventional approaches when clustering sparse biomedical data. By adjusting feature weights and employing consensus clustering, we achieve improved clustering results compared to conventional methods. The PWSC algorithm provides a valuable tool for researchers in the field, enabling more accurate and stable clustering analysis. Its application can enhance our understanding of complex biological systems and contribute to advancements in various biomedical disciplines.
Unveiling promising immunogenic targets in Coxiella burnetii through in silico analysis: paving the way for novel vaccine strategies
Authors: Kodori Mansoor , Amani Jafar , Ahmadi Ali 
Published: December 2023

Abstract
Background
Coxiella burnetii, an intracellular pathogen, serves as the causative agent of zoonotic Q fever. This pathogen presents a significant threat due to its potential for airborne transmission, environmental persistence, and pathogenicity. The current whole-cell vaccine (WCV) utilized in Australia to combat Q fever exhibits notable limitations, including severe adverse reactions and limited regulatory approval for human use. This research employed the reverse vaccinology (RV) approach to uncover antigenic proteins and epitopes of C. burnetii, facilitating the development of more potent vaccine candidates.

Methods
The potential immunogenic proteins derived from C. burnetii RSA493/Nine Mile phase I (NMI) were extracted through manual, automated RV, and virulence factor database (VFDB) methods. Web tools and bioinformatics were used to evaluate physiochemical attributes, subcellular localization, antigenicity, allergenicity, human homology, B-cell epitopes, MHC I and II binding ratios, functional class scores, adhesion probabilities, protein-protein interactions, and molecular docking.

Results
Out of the 1850 proteins encoded by RSA493/NMI, a subset of 178 demonstrated the potential for surface or membrane localization. Following a series of analytical iterations, 14 putative immunogenic proteins emerged. This collection included nine proteins (57.1%) intricately involved in cell wall/membrane/envelope biogenesis processes (CBU_0197 (Q83EW1), CBU_0311 (Q83EK8), CBU_0489 (Q83E43), CBU_0939 (Q83D08), CBU_1190 (P39917), CBU_1829 (Q83AQ2), CBU_1412 (Q83BU0), CBU_1414 (Q83BT8), and CBU_1600 (Q83BB2)). The CBU_1627 (Q83B86 ) (7.1%) implicated in intracellular trafficking, secretion, and vesicular transport, and CBU_0092 (Q83F57) (7.1%) contributing to cell division. Additionally, three proteins (21.4%) displayed uncharacterized functions (CBU_0736 (Q83DJ4), CBU_1095 (Q83CL9), and CBU_2079 (Q83A32)). The congruent results obtained from molecular docking and immune response stimulation lend support to the inclusion of all 14 putative proteins as potential vaccine candidates. Notably, seven proteins with well-defined functions stand out among these candidates.

Conclusions
The outcomes of this study introduce promising proteins and epitopes for the forthcoming formulation of subunit vaccines against Q fever, with a primary emphasis on cellular processes and the virulence factors of C. burnetii.
Does the ultrasound imaging predict lower limb tendinopathy in athletes: a systematic review
Authors: Sharif Faiza , Ahmad Ashfaq , Shabbir Aliha 
Published: December 2023

Abstract
Background
To conduct a systematic review looking into the possibility of US imaging to anticipate and identify future patellar or Achilles tendinopathy symptoms.

Methods
The studies that were taken into consideration for this review were prospective studies that employed baseline US imaging of the patellar OR Achilles tendons in asymptomatic patients and follow-up measures of pain and/or function. Two impartial reviewers evaluated the study’s quality using the Critical Appraisal Skills Programme instrument.

Results
Participants in the included studies in this review came from various sports. The systematic review revealed a link between baseline tendon abnormalities in the US and a higher chance of developing both patellar and Achilles tendinopathy as well as their future occurrence. Nine of the included studies examined the patellar tendon alone, eight the patellar and Achilles tendon together, and four the Achilles tendon exclusively. For both tendons, US administration is done in a largely consistent manner. The tendon abnormalities of tendon thickness, hypoechogenicity and vascularity at baseline were associated with an increased risk of both Achilles and patellar tendinopathy.

Conclusions
This systematic review shows that abnormal tendon structures seen by US in asymptomatic persons can predict the development of tendinopathy.
Relationship between mental health literacy and professional psychological help-seeking attitudes in China: a chain mediation model
Authors: Yang Jingyuan , Li Yunjia , Gao Rui , Chen Hui , Yang Zhihui 
Published: December 2023

Abstract
Background
Mental health literacy is considered an important factor in promoting professional psychological help-seeking attitudes. However, it is important to clarify the emotional and behavioral factors that underlie this association. Drawing from the ABC model of attitudes and the Health Disclosure Decision-Making Model, this study aimed to examine the mediating role of psychological help-seeking stigma and distress disclosure in the relationship between mental health literacy and professional psychological help-seeking attitudes.

Methods
We collected data from 827 participants in seven regions of China (597 female; Mage = 26.019, SD = 5.592 years old) using self-report measures, including the Mental Health Literacy Scale, Questionnaire of Stigma for Seeking Professional Psychological Help, Distress Disclosure Index, and Attitudes Toward Seeking Professional Psychological Help-Short Form. A chain mediation model was built to examine the relationships among mental health literacy, psychological help-seeking stigma, distress disclosure, and professional psychological help-seeking attitudes.

Results
The results of the analyses showed a positive association between mental health literacy and professional psychological help-seeking attitudes, with psychological help-seeking stigma and distress disclosure playing mediating roles in this relationship. Furthermore, even after controlling for participants’ age, gender, and education, the chain mediation effect of psychological help-seeking stigma and distress disclosure on the relationship between mental health literacy and professional psychological help-seeking attitudes was observed among the Chinese population.

Conclusions
These findings underscore the significance of mental health literacy in shaping professional psychological help-seeking attitudes, while emphasizing the need to account for psychological help-seeking stigma and distress disclosure when examining this association. Additionally, the model proposed in this study provides a valuable framework for promoting the utilization of professional mental health services.