bluuebunny/crossref_metadata_2025 huggingface dataset:
Follicular fluid C3a-peptide promotes oocyte maturation through F-actin aggregation
Authors: Yang Ye , Zhao Chun , Chen Beili , Yu Xiaoning , Zhou Yuxi , Ni Danyu , Zhang Xiaolan , Zhang Junqiang , Ling Xiufeng , Zhang Zhiguo , Huo Ran
Published: December 2023

Background

Immature cumulus-oocyte complexes are retrieved to obtain mature oocytes by in vitro maturation (IVM), a laboratory tool in reproductive medicine to obtain mature oocytes. Unfortunately, the efficiency of IVM is not satisfactory. To circumvent this problem, we therefore intended to commence with the composition of ovarian follicular fluid (FF), an important microenvironment influencing oocyte growth. It is well known that FF has a critical role in oocyte development and maturation. However, the components in human FF remain largely unknown, particularly with regard to small molecular peptides.

Results

In current study, the follicular fluid derived from human mature and immature follicles were harvested. The peptide profiles of FF were further investigated by using combined ultrafiltration and LC–MS/MS. The differential peptides were preliminary determined by performing differentially expressed analysis. Human and mouse oocyte culture were used to verify the influence of differential peptides on oocyte development. Constructing plasmids, cell transfecting, Co-IP, PLA etc. were used to reveal the detail molecular mechanism. The results from differentially expressed peptide as well as cultured human and mouse oocytes analyses showed that highly conserved C3a-peptide, a cleavage product of complement C3a, definitely affected oocytes development. Intriguingly, C3a-peptide possessed a novel function that promoted F-actin aggregation and spindle migration, raised the percentage of oocytes at the MII stage, without increasing the chromosome aneuploidy ratio, especially in poor-quality oocytes. These effects of C3a-peptide were attenuated by C3aR morpholino inhibition, suggesting that C3a-peptide affected oocytes development by collaborating with its classical receptor, C3aR. Specially, we found that C3aR co-localized to the spindle with β-tubulin to recruit F-actin toward the spindle and subcortical region of the oocytes through specific binding to MYO10, a key regulator for actin organization, spindle morphogenesis and positioning in oocytes.

Conclusions

Our results provide a new perspective for improving IVM culture systems by applying FF components and also provide molecular insights into the physiological function of C3a-peptide, its interaction with C3aR, and their roles in enabling meiotic division of oocytes.
New chromosome-scale genomes provide insights into marine adaptations of sea snakes (Hydrophis: Elapidae)
Authors: Ludington Alastair J. , Hammond Jillian M. , Breen James , Deveson Ira W. , Sanders Kate L.
Published: December 2023

Background

Sea snakes underwent a complete transition from land to sea within the last ~ 15 million years, yet they remain a conspicuous gap in molecular studies of marine adaptation in vertebrates.

Results

Here, we generate four new annotated sea snake genomes, three of these at chromosome-scale (Hydrophis major,H.ornatusandH. curtus), and perform detailed comparative genomic analyses of sea snakes and their closest terrestrial relatives. Phylogenomic analyses highlight the possibility of near-simultaneous speciation at the root ofHydrophis, and synteny maps show intra-chromosomal variations that will be important targets for future adaptation and speciation genomic studies of this system. We then used a strict screen for positive selection in sea snakes (against a background of seven terrestrial snake genomes) to identify genes over-represented in hypoxia adaptation, sensory perception, immune response and morphological development.

Conclusions

We provide the best reference genomes currently available for the prolific and medically important elapid snake radiation. Our analyses highlight the phylogenetic complexity and conserved genome structure withinHydrophis. Positively selected marine-associated genes provide promising candidates for future, functional studies linking genetic signatures to the marine phenotypes of sea snakes and other vertebrates.
Geroprotector drugs and exercise: friends or foes on healthy longevity?
Authors: Elliehausen Christian J. , Anderson Rozalyn M. , Diffee Gary M. , Rhoads Timothy W. , Lamming Dudley W. , Hornberger Troy A. , Konopka Adam R.
Published: December 2023

Physical activity and several pharmacological approaches individually combat age-associated conditions and extend healthy longevity in model systems. It is tantalizing to extrapolate that combining geroprotector drugs with exercise could extend healthy longevity beyond any individual treatment. However, the current dogma suggests that taking leading geroprotector drugs on the same day as exercise may limit several health benefits. Here, we review leading candidate geroprotector drugs and their interactions with exercise and highlight salient gaps in knowledge that need to be addressed to identify if geroprotector drugs can have a harmonious relationship with exercise.
CYP4V2 rs56413992 C > T was associated with the risk of coronary heart disease in the Chinese Han population: a case–control study
Authors: Huang Kang , Ma Tianyi , Li Qiang , Zhong Zanrui , Zhou Yilei , Zhang Wei , Qin Ting , Tang Shilin , Zhong Jianghua , Lu Shijuan
Published: December 2023

Purpose

The research aimed to detect the association between single nucleotide polymorphisms (SNPs) in CYP4V2 gene and coronary heart disease (CHD) risk.

Methods

This case–control study included 487 CHD subjects and 487 healthy individuals. Logistic regression was performed to analyze the connection between five SNPs in CYP4V2 (rs1398007, rs13146272, rs3736455, rs1053094, and rs56413992) and CHD risk, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the connection.

Results

As a result, we found that rs56413992 T allele (OR = 1.36, 95% CI = 1.09–1.70, p = 0.007) and CT genotype (OR = 1.40, 95% CI = 1.06–1.83, p = 0.017) were significantly associated with an increased risk of CHD in the overall analysis. Precisely, rs56413992 was linked to an elevated risk of CHD in people aged > 60, males, smokers and drinkers. The study also indicated that rs1398007 was linked to an increased CHD risk in drinkers. In addition, rs1053094 was correlated with a decreased risk of CHD complicated with diabetes mellitus (DM), and rs1398007 was correlated with a decreased risk of CHD complicated with hypertension (HTN).

Conclusion

This study was the first to experimentally demonstrate that CYP4V2 rs56413992 was associated with the risk of CHD, which will provide a certain reference for revealing the pathogenesis of CHD.
Access to infertility care in Brazil: validation of a questionnaire for a bioethical discussion
Authors: Oppenheimer Drauzio , Caldas Christiane Peres , Rego Francisca , Nunes Rui
Published: December 2023

Background

The World Health Organization characterizes infertility as a disease since 2009; however, in many countries, reproductive health is not prioritized. Characterizing a target population and knowing the barriers to accessing reproductive care may allow for a broadening of the discussion on how to provide equal opportunities. The objective of this study was to develop and validate a questionnaire that seeks to identify socioeconomic and cultural characteristics of Brazilian infertile couples to open the discussion on the principle of fair access to health.

Methods

(1) literature review in the main databases, (2) questionnaire elaboration by researchers within the areas of human reproduction and bioethics, concerned with content adequacy and comprehension, using the Google Forms online platform, (3) pilot study - the questionnaire was applied to 54 couples, over 18 years of age, that were seeking treatment for infertility and accepted to participate in the study and (4) statistical analysis - for continuous numerical variables, mean, standard deviation and 95% CI of the means were presented. For discrete numerical variables, median, interquartile range, minimum and maximum were presented.

Results

Forty-four questionnaires were fully completed and with adequate answers. The questionnaire proved to be objective and easy to understand. It was possible to obtain information on education, race of the couple, the impact of infertility on the couple’s life, socioeconomic conditions, and the main difficulties in accessing medical care for treatment of infertility.

Conclusion

The questionnaire proved to be feasible in collecting appropriate information to characterize a target population and the only limitation was that there was no academic expert evaluation prior to the pilot test.
Human exposure to diesel exhaust induces CYP1A1 expression and AhR activation without a coordinated antioxidant response
Authors: Friberg M. , Behndig A. F. , Bosson J. A. , Muala Ala , Barath S. , Dove R. , Glencross D. , Kelly F. J. , Blomberg A. , Mudway I. S. , Sandström T. , Pourazar J.
Published: December 2023

Background

Diesel exhaust (DE) induces neutrophilia and lymphocytosis in experimentally exposed humans. These responses occur in parallel to nuclear migration of NF-κB and c-Jun, activation of mitogen activated protein kinases and increased production of inflammatory mediators. There remains uncertainty regarding the impact of DE on endogenous antioxidant and xenobiotic defences, mediated by nuclear factor erythroid 2-related factor 2 (Nrf2) and the aryl hydrocarbon receptor (AhR) respectively, and the extent to which cellular antioxidant adaptations protect against the adverse effects of DE.

Methods

Using immunohistochemistry we investigated the nuclear localization of Nrf2 and AhR in the epithelium of endobronchial mucosal biopsies from healthy subjects six-hours post exposure to DE (PM10, 300 µg/m3) versus post-filtered air in a randomized double blind study, as a marker of activation. Cytoplasmic expression of cytochrome P450s, family 1, subfamily A, polypeptide 1 (CYP1A1) and subfamily B, Polypeptide 1 (CYP1B1) were examined to confirm AhR activation; with the expression of aldo–keto reductases (AKR1A1, AKR1C1 and AKR1C3), epoxide hydrolase and NAD(P)H dehydrogenase quinone 1 (NQO1) also quantified. Inflammatory and oxidative stress markers were examined to contextualize the responses observed.

Results

DE exposure caused an influx of neutrophils to the bronchial airway surface (p = 0.013), as well as increased bronchial submucosal neutrophil (p < 0.001), lymphocyte (p = 0.007) and mast cell (p = 0.002) numbers. In addition, DE exposure enhanced the nuclear translocation of the AhR and increased the CYP1A1 expression in the bronchial epithelium (p = 0.001 and p = 0.028, respectively). Nuclear translocation of AhR was also increased in the submucosal leukocytes (p < 0.001). Epithelial nuclear AhR expression was negatively associated with bronchial submucosal CD3 numbers post DE (r = −0.706, p = 0.002). In contrast, DE did not increase nuclear translocation of Nrf2 and was associated with decreased NQO1 in bronchial epithelial cells (p = 0.02), without affecting CYP1B1, aldo–keto reductases, or epoxide hydrolase protein expression.

Conclusion

These in vivo human data confirm earlier cell and animal-based observations of the induction of the AhR and CYP1A1 by diesel exhaust. The induction of phase I xenobiotic response occurred in the absence of the induction of antioxidant or phase II xenobiotic defences at the investigated time point 6 h post-exposures. This suggests DE-associated compounds, such as polycyclic aromatic hydrocarbons (PAHs), may induce acute inflammation and alter detoxification enzymes without concomitant protective cellular adaptations in human airways.
Technical aspects of reconstruction for inadequate left atrial cuff in lung transplantation
Authors: Citak Sevinc , Cardak Murat Ersin
Published: December 2023

Objective

Lung transplantation is the only life-saving treatment for lung diseases that do not respond to medical treatment. Heart-lung harvesting requires a careful procedure to protect an adequate donor left atrial cuff around the junction of the superior and inferior pulmonary veins. This study aims to describe inadequate left atrial cuff during harvest and techniques of reconstruction at the threshold of literature.

Methods

Left atrial cuff complications were retrospectively analyzed in consecutive lung transplant procedures between December 2016 and December 2021. Donor and patient demographics, reconstruction material and method of application and postoperative follow-up were examined.

Results

In the study period, 84 consecutive lung transplant procedures were performed. Reconstruction of the inadequate left atrial cuff was 3.7% (6/162) for atrial anastomoses. However, the inadequate left atrial cuff was 9.1% (5/55) in heart-lung harvesting. Donor aorta graft was used in 4 patients and Dacron mesh was used on the bilateral atrial cuff in one patient. Hospital mortality occurred in one patient. One patient died 6 months later due to antibody-mediated rejection. The follow-ups of the other three patients are continuing without any problems.

Conclusions

Inadequate left atrial cuff complications occurring in heart-lung harvest seem to be more common than in the literature. Techniques of reconstruction for the inadequate left atrial cuff is vital for the patient who has reached irreversible progress in surgery for the recipient, as well as increasing the number of organs.
The pregnancy and oncology outcome of fertility-sparing management for synchronous primary neoplasm of endometrium and ovary
Authors: Gama Qujia , Luo Shuhan , Wu Pengfei , Wang Lulu , Liu Sijia , Zhang Hongwei , Sun Li , Wang Yiqin , Yu Min , Chen Xiaojun , Shan Weiwei , Luo Xuezhen
Published: December 2023

Purpose

To investigate the efficacy of fertility-preserving treatment for young women with synchronous primary neoplasm of endometrium and ovary.

Methods

We retrospectively reviewed eight patients with concurrent primary grade 1 presumed stage IA endometrioid endometrial adenocarcinoma (EEA) or endometrial atypical hyperplasia (EAH) and primary stage I ovarian tumors who underwent fertility-sparing treatment in the Obstetrics and Gynecology Hospital of Fudan University between April 2016 and December 2022.

Results

Synchronous endometrial and ovarian cancers (SEOC) accounted for 50% of these eight patients. The median age of patients was 30.5 years (range, 28–34 years). None of them received chemotherapy. The median treatment time was 4 months (range, 3–8 months). 87.5% (7/8) cases achieved complete response (CR), and the median time to CR was 3.8 months (range, 1.5–7.7 months). Among patients who got CR, none of them showed any signs of recurrence. Pregnancies and successful deliveries were achieved in 4 of 5 patients. Till September 2023, the median follow-up period was 50.5 months (range:15.2–85.2 months).

Conclusion

Fertility-sparing treatment is feasible for highly selected patients with synchronous neoplasm of the endometrium and ovary, but strict screening and monitoring are mandatory. Though the results of our limited cases are encouraging, long follow-up and more clinical data are required. Enrolled patients must be fully informed of the risks during conservative treatment.
SMAD4 variants and its genotype–phenotype correlations to juvenile polyposis syndrome
Authors: Cao Kimberley , Plazzer John-Paul , Macrae Finlay
Published: December 2023

Background

Juvenile polyposis syndrome (JPS), a rare autosomal dominant syndrome, affects one per 100 000 births, increasing lifetime cancer risk by 9 – 50%. Around 40–60% of JPS cases are caused by disease-causing variants (DCV) in SMAD4 or BMPR1A genes, of which SMAD4 accounts for 20–30%.

Objectives

To characterise genotype–phenotype correlations between sites and types of variants within SMAD4 to JPS phenotypes, to inform diagnosis, screening, and management of JPS.

Search methods

Online search databases utilised included Ovid MEDLINE, Embase Classic + Embase and PubMed, using search terms classified by MeSH on Demand. Adjacency operators, word truncation and Boolean operators were employed. 110 articles were included in the review, collating 291 variants from the literature.

Results

In SMAD4 + JPS patients, most variants are located around SMAD4’s MH2 domain (3’ end). Extracolonic involvement, massive gastric polyposis and a more aggressive phenotype have been associated with SMAD4 + JPS, predisposing to gastric cancer. This has contributed to an overall higher incidence of GI cancers compared to other genes causing JPS, with DCVs mostly all within the MH2 domain. Genetically related allelic disorders of SMAD4 also have variants in this region, including hereditary haemorrhagic telangiectasia (HHT) alongside SMAD4 + JPS, and Myhre syndrome, independent of JPS. Similarly, with DCVs in the MH2 domain, Ménétrier’s disease, hypertrophic osteoarthropathy and juvenile idiopathic arthritis have been seen in this population, whereas cardiac pathologies have occurred both alongside and independently of SMAD4 + JPS with DCVs in the MH1 domain.

Conclusion

Truncating and missense variants around the MH2 region of SMAD4 are most prevalent and pathogenic, thus should undergo careful surveillance. Given association with extracolonic polyposis and higher GI cancer risk, endoscopic screening should occur more frequently and at an earlier age in SMAD4 + JPS patients than in patients with other causative genes, with consideration of Ménétrier’s disease on upper GI endoscopy. In addition, HHT should be evaluated within 6 months of diagnosis, alongside targeted clinical examination for extraintestinal manifestations associated with SMAD4 + JPS. This review may help modify clinical diagnosis and management of SMAD4 + JPS patients, and aid pathogenicity classification for SMAD4 DCVs through a better understanding of the phenotypes.
Additional predictive value of optic nerve sheath diameter for neurological prognosis after cardiac arrest: a prospective cohort study
Authors: Verhulst Marlous M. L. H. , Visser Iris M. , Keijzer Hanneke M. , de Kruijf Nicole L. M. , Peters Erwin J. G. , Wilbers Thom , Peelen Roel V. , Hofmeijer Jeannette , Blans Michiel J.
Published: December 2023

Background

The goal is to estimate the additional value of ultrasonographic optic nerve sheath diameter (ONSD) measurement on days 1–3, on top of electroencephalography (EEG), pupillary light reflexes (PLR), and somatosensory evoked potentials (SSEP), for neurological outcome prediction of comatose cardiac arrest patients. We performed a prospective longitudinal cohort study in adult comatose patients after cardiac arrest. ONSD was measured on days 1–3 using ultrasound. Continuous EEG, PLR, and SSEP were acquired as standard care. Poor outcome was defined as cerebral performance categories 3–5 at 3–6 months. Logistic regression models were created for outcome prediction based on the established predictors with and without ONSD. Additional predictive value was assessed by increase in sensitivity for poor (at 100% specificity) and good outcome (at 90% specificity).

Results

We included 100 patients, 54 with poor outcome. Mean ONSD did not differ significantly between patients with good and poor outcome. Sensitivity for predicting poor outcome increased by adding ONSD to EEG and SSEP from 25% to 41% in all patients and from 27% to 50% after exclusion of patients with non-neurological death.

Conclusions

ONSD on days 1–3 after cardiac arrest holds potential to add to neurological outcome prediction.

Trialregistration: clinicaltrials.gov, NCT04084054. Registered 10 September 2019, https://www.clinicaltrials.gov/study/NCT04084054.
Prediction of mortality in secondary peritonitis: a prospective study comparing p-POSSUM, Mannheim Peritonitis Index, and Jabalpur Peritonitis Index
Authors: Pathak Akshant Anil , Agrawal Vivek , Sharma Naveen , Kumar Karan , Bagla Chinmay , Fouzdar Aakash
Published: December 2023

Background

Risk scoring systems are required to allow accurate prognostication, compare outcomes of surgery, and allow patients to make informed decisions about their health. This prospective study compares the p-POSSUM (Portsmouth Modification to Physiological and Operative Severity Score for Enumeration of Mortality), Mannheim Peritonitis Index, and Jabalpur Peritonitis Index for their utility in predicting mortality in patients with peritonitis.

Methods

Perioperative data was collected from 235 patients with secondary peritonitis and used to calculate p-POSSUM, MPI, and JPI scores. The accuracy of the 3 scores was compared using receiver operator characteristic curves.

Results

p-POSSUM and Mannheim Peritonitis Index were similar in their accuracy with area under the curve (AUC) values of 0.756 and 0.757. Jabalpur Peritonitis Index had an AUC of 0.665.

Conclusion

p-POSSUM and Mannheim Peritonitis Index can be used to predict mortality in patients with secondary peritonitis. Jabalpur Peritonitis Index is not suited for this purpose. Further studies are required to improve the diagnostic performance of p-POSSUM and MPI in patients with secondary peritonitis.
Description of a nationwide structure for monitoring nosocomial outbreaks of (highly resistant) microorganisms in the Netherlands: characteristics of outbreaks in 2012–2021
Authors: Woudt Sjoukje HS , Schoffelen Annelot F , Frakking Florine NJ , Reuland E Ascelijn , Severin Juliëtte A , den Drijver Marije , Haenen Anja , Nonneman Marga MG , Notermans Daan W , aan de Stegge Desiree CM , de Stoppelaar Sacha F , Vandenbroucke-Grauls Christina MJE , de Greeff Sabine C
Published: December 2023

Background

Before 2012, established national surveillance systems in the Netherlands were not able to provide a timely, comprehensive epidemiological view on nosocomial outbreaks. The Healthcare-associated Infections and AntiMicrobial Resistance Monitoring Group (SO-ZI/AMR) was initiated in 2012 for timely national nosocomial outbreak monitoring and risk assessment. This paper aims to describe the achievements of the SO-ZI/AMR by presenting characteristics of outbreaks reported in 2012–2021.

Methods

Hospitals and, since 2015, long-term care facilities (LTCF) were requested to report outbreaks when (1) continuity of care was threatened, or (2) transmission continued despite control measures. A multi-disciplinary expert panel (re-)assessed the public health risk of outbreaks during monthly meetings, using 5 severity phases and based on data collected via standardised questionnaires. We descriptively studied the panel’s consensus-based severity classification, distribution of (highly resistant) microorganisms, and duration and size of outbreaks between April 2012 and December 2021.

Results

In total, 353 hospital outbreaks and 110 LTCF outbreaks were reported. Most outbreaks (hospitals: n = 309 (88%), LTCF: n = 103 (94%)) did not progress beyond phase 1 (no public health implications, outbreak expected to be controlled within two months), one hospital outbreak reached phase 4 (insufficient/ineffective response: possible public health threat, support offered). Highly resistant microorganisms (HRMO) were involved in 269 (76%) hospital and 103 (94%) LTCF outbreaks. Most outbreaks were caused by methicillin-resistant Staphylococcus aureus (MRSA; n = 93 (26%) in hospitals, n = 80 (72%) in LTCF), vancomycin-resistant Enterococcus faecium (VRE; n = 116 (33%) in hospitals, n = 2 (2%) in LTCF) and highly resistant Enterobacterales (n = 41 (12%) in hospitals, n = 20 (18%) in LTCF). Carbapenemase-producing gram-negative bacteria were involved in 32 (9.1%) hospital and five (4.5%) LTCF outbreaks. In hospitals, VRE outbreaks had the longest duration (median 2.3; range 0.0-22.8 months) and widest range of affected patients (median 9; range 2-483).

Conclusions

The SO-ZI/AMR provided national insight into the characteristics of nosocomial outbreaks over the past decade. HRMO outbreaks – mostly caused by MRSA, VRE (in hospitals) and highly resistant Enterobacterales – occurred regularly, but most of them were controlled quickly and did not develop into a public health threat. The SO-ZI/AMR has become a solid monitoring body, essential to assess risks and raise awareness of potential HRMO threats.
Food insecurity, coping strategies, and resilience of agricultural cooperative members during COVID-19 in West Africa
Authors: Kpadé Cokou Patrice , Bélanger Marie-Christine , Laplante Catherine , Lambert Constance , Bocoum Ibrahima
Published: December 2023

Background

Lockdown measures of COVID-19 have had different repercussions on the well-being of households in West Africa depending on their resilience capacity. This study compares the dynamic of households’ food insecurity during COVID-19 pandemic according to their membership in different types of agricultural cooperatives in four West African countries, namely Ghana, Mali, Ivory Coast, and Senegal.

Methodology

We used data collected from 1270 members of agricultural cooperatives and regression analyses, to understand the link between the nature of their cooperatives and the food insecurity dynamic of their household, while controlling for other sociodemographic characteristics. Cooperative were categorized either “active” or “poorly/not active” depending on their capacity to conduct initiatives that address the needs of their members, to maintain communication between leaders and members, the participation of members to decisions, and their possession of a good understanding of business management. Food insecurity is measured using the Food Insecurity Experience Scale (FIES) and the Coping Strategy Index (CSI). Respondents were asked to answer questions related to their food security status for the period before and during the pandemic.

Results

The COVID-19 pandemic has adversely affected respondents' food security status. These effects varied according to the severity of sanitary measures implemented and to the dynamism of cooperatives. Households of poorly or not active cooperatives have experienced more food insecurity in Ivory Coast and Senegal than those who were members of active cooperatives; in Ghana the effects were significant but similar in both types of cooperatives. Members of both cooperatives in Mali appear to have been less affected than members in other countries. Furthermore, households of poorly/not active cooperatives have used more severe coping strategies in Ivory Coast, Ghana, and Senegal during the pandemic.

Conclusions

Strong collaboration and support provided by cooperatives can contribute to increase the resilience capacity of their members to shocks such as the COVID-19 pandemic.
The role of pyroptosis and gasdermin family in tumor progression and immune microenvironment
Authors: Li Mengyuan , Jiang Ping , Yang Yuhan , Xiong Liting , Wei Shuhua , Wang Junjie , Li Chunxiao
Published: December 2023

Pyroptosis, an inflammatory programmed cell death, distinguishes itself from apoptosis and necroptosis and has drawn increasing attention. Recent studies have revealed a correlation between the expression levels of many pyroptosis-related genes and both tumorigenesis and progression. Despite advancements in cancer treatments such as surgery, radiotherapy, chemotherapy, and immunotherapy, the persistent hallmark of cancer enables malignant cells to elude cell death and develop resistance to therapy. Recent findings indicate that pyroptosis can overcome apoptosis resistance amplify treatment-induced tumor cell death. Moreover, pyroptosis triggers antitumor immunity by releasing pro-inflammatory cytokines, augmenting macrophage phagocytosis, and activating cytotoxic T cells and natural killer cells. Additionally, it transforms “cold” tumors into “hot” tumors, thereby enhancing the antitumor effects of various treatments. Consequently, pyroptosis is intricately linked to tumor development and holds promise as an effective strategy for boosting therapeutic efficacy. As the principal executive protein of pyroptosis, the gasdermin family plays a pivotal role in influencing pyroptosis-associated outcomes in tumors and can serve as a regulatory target. This review provides a comprehensive summary of the relationship between pyroptosis and gasdermin family members, discusses their roles in tumor progression and the tumor immune microenvironment, and analyses the underlying therapeutic strategies for tumor treatment based on pyroptotic cell death.
Triangulating nutrigenomics, metabolomics and microbiomics toward personalized nutrition and healthy living
Authors: Lagoumintzis George , Patrinos George P.
Published: December 2023

The unique physiological and genetic characteristics of individuals influence their reactions to different dietary constituents and nutrients. This notion is the foundation of personalized nutrition. The field of nutrigenetics has witnessed significant progress in understanding the impact of genetic variants on macronutrient and micronutrient levels and the individual's responsiveness to dietary intake. These variants hold significant value in facilitating the development of personalized nutritional interventions, thereby enabling the effective translation from conventional dietary guidelines to genome-guided nutrition. Nevertheless, certain obstacles could impede the extensive implementation of individualized nutrition, which is still in its infancy, such as the polygenic nature of nutrition-related pathologies. Consequently, many disorders are susceptible to the collective influence of multiple genes and environmental interplay, wherein each gene exerts a moderate to modest effect. Furthermore, it is widely accepted that diseases emerge because of the intricate interplay between genetic predisposition and external environmental influences. In the context of this specific paradigm, the utilization of advanced "omic" technologies, including epigenomics, transcriptomics, proteomics, metabolomics, and microbiome analysis, in conjunction with comprehensive phenotyping, has the potential to unveil hitherto undisclosed hereditary elements and interactions between genes and the environment. This review aims to provide up-to-date information regarding the fundamentals of personalized nutrition, specifically emphasizing the complex triangulation interplay among microbiota, dietary metabolites, and genes. Furthermore, it highlights the intestinal microbiota's unique makeup, its influence on nutrigenomics, and the tailoring of dietary suggestions. Finally, this article provides an overview of genotyping versus microbiomics, focusing on investigating the potential applications of this knowledge in the context of tailored dietary plans that aim to improve human well-being and overall health.
Randomised controlled trial of neurostimulation for symptoms of anorexia nervosa (TRENA study): study protocol
Authors: Harvey Anna J. , Madden Sloane , Rodgers Anthony , Bull Michael , Chatterton Mary Lou , Hadzi-Pavlovic Dusan , Loo Colleen K. , Martin Donel M.
Published: December 2023

Background

Anorexia nervosa (AN) has amongst the highest mortality rates and the highest treatment costs of any psychiatric disorder. Recently, interest in non-invasive brain stimulation as a novel treatment for AN has grown. These include repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS).

Methods

This double-blind, randomised sham-controlled trial will compare the relative acceptability and efficacy of tDCS and rTMS in people with AN. 70 participants will be randomised to active or sham tDCS, or active or sham rTMS treatment (2:1:2:1 ratio) over an 8-week treatment period. Participants will receive treatment as usual across the study duration. The primary outcomes are change on the Eating Disorder Examination Questionnaire and treatment acceptability. Secondary outcomes will include change in weight, cognition, mood, interpersonal functioning, and quality of life. Following the 8-week assessment, all participants will have the option of receiving an additional 12 weeks of at-home tDCS. A follow-up assessment will be conducted at 20 weeks post treatment.

Discussion

Research into non-invasive brain stimulation as treatments for AN has potential to improve clinical outcomes for patients by comparing the relative efficacy and acceptability of both treatment modalities in the inpatient and at-home setting (i.e., for at-home tDCS) results from this study will provide important information for informing future larger clinical trials of these treatments for AN.

Trial registration

ClinicalTrials.gov Identifier: NCT05788042.
Cross-cultural adaptation and validation of the Mental Health Quality of Life (MHQoL) questionnaire in a Chinese-speaking population with chronic musculoskeletal pain
Authors: Wang Jialin , Wang Ruirui , Zhao Peng , Han Tianran , Li Meng , He Yuwei , Liu Yan
Published: December 2023

Background

The Mental Health Quality of Life (MHQoL) questionnaire is concise and suitable for rapid assessment of CMP (chronic musculoskeletal pain) patients in primary care. However, there is a lack of Chinese versions of the MHQoL.

Objective

To cross-culturally translate the MHQoL into Chinese and to assess its psychometric properties in Chinese-speaking patients with CMP.

Methods

The MHQoL was translated into Chinese according to the International Guidelines for the Cross-Cultural Adaptation of Self-Report Measures. 171 CMP patients were recruited to receive the Chinese versions of the MHQoL, SF-36, and HADS tests, and the MHQoL was retested seven days later.

Result

The Chinese version of MHQoL had good retest reliability (MHQoL-7D: ICC = 0.971; MHQoL-VAS: ICC = 0.988) and internal consistency (Cronbach’s alpha = 0.829). It showed a moderate correlation with the SF-36 total score (r=-0.509); the MHQoL-VAS moderately correlated with the Hospital Anxiety Depression Scale (r=-0.548). The MHQoL-7D showed no correlations with the SF-36’s PF (r=-0.083) and BP (r=-0.170), weak correlations with RP (r=-0.284), RE (r=-0.298), and SF (r=-0.380), and moderate-to-strong correlations with GH (r=-0.638), VT (r=-0.480), and MH (r=-0.632).

Conclusion

The Chinese version of the MHQoL can be used in clinical practice and research in Chinese-speaking CMP patients.
A novel BRAF::PTPRN2 fusion in meningioma: a case report
Authors: Sadagopan Nishanth S. , Nandoliya Khizar R. , Youngblood Mark W. , Horbinski Craig M. , Ahrendsen Jared T. , Magill Stephen T.
Published: December 2023

Gene fusion events have been linked to oncogenesis in many cancers. However, gene fusions in meningioma are understudied compared to somatic mutations, chromosomal gains/losses, and epigenetic changes. Fusions involving B-raf proto-oncogene, serine/threonine kinase (BRAF) are subtypes of oncogenic BRAF genetic abnormalities that have been reported in certain cases of brain tumors, such as pilocytic astrocytomas. However, BRAF fusions have not been recognized in meningioma. We present the case of an adult female presenting with episodic partial seizures characterized by déjà vu, confusion, and cognitive changes. Brain imaging revealed a cavernous sinus and sphenoid wing mass and she underwent resection. Histopathology revealed a World Health Organization (WHO) grade 1 meningioma. Genetic profiling with next generation sequencing and microarray analysis revealed an in-frame BRAF::PTPRN2 fusion affecting the BRAF kinase domain as well as chromothripsis of chromosome 7q resulting in multiple segmental gains and losses including amplifications of cyclin dependent kinase 6 (CDK6), tyrosine protein-kinase Met (MET), and smoothened (SMO). Elevated pERK staining in tumor cells provided evidence of activated mitogen-activated protein kinase (MAPK) signaling. This report raises the possibility that gene fusion events may be involved in meningioma pathogenesis and warrant further investigation.
Pandemic-related challenges for team leadership in ECEC centres in Germany
Authors: Lattner Katrin , Strehmel Petra
Published: December 2023

This article investigates Early Childhood Education and Care (ECEC) leadership during the COVID-19 pandemic. The focus is on ECEC leaders’ perceptions of team leadership during the COVID-19 pandemic in Germany. The purpose of the study is to increase understanding of the team-related challenges ECEC leaders have been confronted with, how they have been experienced and mastered. Therefore, two qualitative studies were designed (Hamburg, Leipzig). A total of 55 ECEC leaders from different federal states were surveyed in guideline-based qualitative interviews (Leipzig study: n = 20 ECEC leaders; Hamburg study: n = 35 ECEC leaders) and analysed with a qualitative content analysis. The results show how teamwork changed under the pandemic conditions and what challenges the leaders faced, including a lack of staff (due to e. g. quarantine, disease), structural separation of teams, lack of communication, additional tasks (political regulations), and missing collaboration with parents. The results indicate that not only ECEC leaders are required to organise team development activities on a regular basis or to reflect on the experiences of the pandemic within heterogeneous teams but also setting providers and sectoral policies are called upon to support ECEC centres in crisis according to their needs.
DNA from non-viable bacteria biases diversity estimates in the corals Acropora loripes and Pocillopora acuta
Authors: Dungan Ashley M. , Geissler Laura , Williams Amanda S. , Gotze Cecilie Ravn , Flynn Emily C. , Blackall Linda L. , van Oppen Madeleine J. H.
Published: December 2023

Background

Nucleic acid-based analytical methods have greatly expanded our understanding of global prokaryotic diversity, yet standard metabarcoding methods provide no information on the most fundamental physiological state of bacteria, viability. Scleractinian corals harbour a complex microbiome in which bacterial symbionts play critical roles in maintaining health and functioning of the holobiont. However, the coral holobiont contains both dead and living bacteria. The former can be the result of corals feeding on bacteria, rapid swings from hyper- to hypoxic conditions in the coral tissue, the presence of antimicrobial compounds in coral mucus, and an abundance of lytic bacteriophages.

Results

By combining propidium monoazide (PMA) treatment with high-throughput sequencing on six coral species (Acropora loripes,A. millepora,A. kenti,Platygyra daedalea,Pocillopora acuta, andPorites lutea) we were able to obtain information on bacterial communities with little noise from non-viable microbial DNA. Metabarcoding of the 16S rRNA gene showed significantly higher community evenness (85%) and species diversity (31%) in untreated compared with PMA-treated tissue forA. loripesonly. While PMA-treated coral did not differ significantly from untreated samples in terms of observed number of ASVs, > 30% of ASVs were identified in untreated samples only, suggesting that they originated from cell-free/non-viable DNA. Further, the bacterial community structure was significantly different between PMA-treated and untreated samples forA. loripesandP. acutaindicating that DNA from non-viable microbes can bias community composition data in coral species with low bacterial diversity.

Conclusions

Our study is highly relevant to microbiome studies on coral and other host organisms as it delivers a solution to excluding non-viable DNA in a complex community. These results provide novel insights into the dynamic nature of host-associated microbiomes and underline the importance of applying versatile tools in the analysis of metabarcoding or next-generation sequencing data sets.
Generalized dystonia following resuscitation from a cardiac arrest: a case report and review of the literature
Authors: Mbodji Ahmadou Bamba , Fall Maouly , Gaye Ndiaga Matar , Ka Mamadou , Dione Jean Claude , Ndiaye Moustapha , Diop Amadou Gallo
Published: December 2023

Background

A wide variety of movement disorders can be observed after cerebral hypoxia, including akineto-hypertonic syndrome and dystonia. Post-anoxic dystonia is a rare clinical syndrome that is not widely reported in the literatures. It is thought to be related to cerebral hypoxia leading to ischaemia of the basal ganglia.

Case description

We report a case of an 11-year-old girl who represented with generalized dystonia following resuscitation from a cardiac arrest after open heart surgery. Brain MRI showed basal ganglia hypersignals in T2-FLAIR (fluid attenuated inversion recovery) weighted sequence and in the diffusion sequence without restriction of ACD in favour of subacute ischemic lesions. Treated with oral baclofen, the evolution was favourable with regression of the dystonia.

Conclusion

It is often difficult to accurately predict the final neurological outcome of a patient who has survived cardiac arrest. Baclofen and anticholinergic can be used for the treatment for dystonia post-cerebral hypoxia.
Post-traumatic stress disorder in adolescents during the COVID-19 pandemic: a cross-sectional Tunisian study
Authors: Boudabous Jaweher , Kerkeni Ali , Kraiem Mayssa , Ayadi Hela , Moalla Yousr
Published: December 2023

Objectives

Evaluate the prevalence of post-traumatic stress disorder (PTSD) on Tunisian adolescents enrolled in secondary schools during the COVID-19 pandemic and to identify associated factors.

Methods

We conducted a cross-sectional, descriptive, and analytic study on a sample of Tunisian adolescents. Participants were randomly selected from two schools in the region of Hamma (southern of Tunisia). This survey took place during the period extending from 5 March to 26 May 2021. Students were asked to complete a pre-established information sheet which contains questions about socio-demographic features, medical history, knowledge about the pandemic of COVID-19, and personal or family history of being infected with this virus. The Child PTSD Symptom Scale (CPSS) was used to screen for PTSD among students.

Results

The sample was composed of 326 students (92 boys and 234 girls; mean age 16.65 years). The prevalence of PTSD was 37.4% according to the CPSS. Adolescents had more PTSD symptoms when they lived in a conflictual family atmosphere (AOR = 3.1 [1.4–6.9]). Moreover, adolescents who were infected by the virus, or whose relatives were contaminated or dead because of the COVID-19 infection, were more likely to develop PTSD symptoms. We stated that students who estimated that their knowledge about the COVID-19 pandemic were insufficient had a significant  higher risk for PTSD (AOR = 2.5 [1.4–4.6]).

Conclusion

Students seemed to have high frequency of PTSD symptoms during the COVID-19 pandemic. The identification of risk and protective factors are interesting to guide screening and prevention actions.

Key points

• Adolescents were vulnerable to psychological distress during COVID-19 pandemic, they were more exposed to develop post-traumatic stress disorder.

• A total of 37.4% was the prevalence of PTSD among Tunisian adolescents. Sufficient information about the pandemic was protective. Conflictual family atmosphere constitutes a risk factor.

• Family and social efforts should be directed toward supporting teenagers to cope with the pandemics’ mental health burden.
Adolescents and Young Adults With Cancer: CNS Tumors
Authors: Wu Jing , Heidelberg R. Elyse , Gajjar Amar
Published: December 2023

Tumors of CNS are common in adolescents and young adults (AYAs). As the second leading cause of cancer-related death, CNS tumors in AYAs require improved clinical management. In this review, we discussed the current diagnostic approaches and recommended management strategies for malignant tumors in adult-type (IDH-mutant gliomas) and pediatric-type gliomas (pediatric high-grade gliomas), ependymoma and medulloblastoma, which commonly occur in AYAs. The impact of advanced molecular diagnostic approaches on the understanding of tumor biology of AYA CNS tumors is emphasized. To enhance participation in clinical trials, which poses a unique challenge in AYAs with CNS tumors, we propose encouraging referrals to neuro-oncology specialty care and improving collaboration between oncologists who care for both pediatric and adult patients. This will ensure better representation of AYA patients in research studies. Finally, we discussed the importance of considering neurocognitive and psychological function in AYAs with CNS tumor.
Pascal without Apology
Authors: Braider Christopher
Published: December 2023

We’ve always had two Pascals, one apologetic, the other startlingly unapologetic. The unapologetic Pascal is the merciless, proto-ethnographic observer of human psychology and human social arrangements whose sardonic picture of what he calls the wretchedness of life without God is summed up in the strikingly Hobbesian chiasmus “Lacking the might to compel obedience to right, we’ve made it right to compel obedience to might.” However, Pascal turns demoralizing insights like this to apologetic purposes by showing how they’re the natural effect of a lack of specifically Christian belief. The question this essay poses against the background of the conflicted history of Pascalian exegesis is, how should we read the Pensées? The answer proposed is that we should do so in the dialectical terms that Pascal’s characteristic resort to chiasmoi like this one suggest. The result takes the form of a three-cornered conversation that links Pascalian thinking not only to the Hobbes of Leviathan but to the Hegel of the Phenomenology of Spirit and the Elements of Right and to the Wittgenstein of the late, sadly fruitless notebook On Certainty.
Factors Associated with Improving Appropriate Medical Sharps Disposal Practice Among Diabetic Patients Using Insulin Therapy
Authors: Herardi Ryan , Djajawiguna Hafidz Naeriansyah , Wahyuningsih Sri , Kshanti Ida Ayu , Medina Shahnaz , Praditya Lingga Etantyo
Published: December 2023

Background Diabetic patients are always in contact with medical sharps, such as pen needles, lancets, and syringes. Sometimes, patients improperly dispose of these items and cause needle stick injuries. This study aimed to identify factors that improve appropriate manner in which individuals with diabetes who require insulin therapy dispose of medical sharps. Methods In December 2019, a cross-sectional investigation was undertaken amongst insulin therapy-dependent diabetic patients visiting Jakarta’s Fatmawati General Hospital. A questionnaire was formulated to appraise medical sharps’ disposal procedure. The data gathered the questionnaire, including age, gender, educational level, employment status, length of time as a diabetic, duration of insulin treatment, and receipt of formal medical training, were also recorded. Results Of 103 diabetic patients, 77.3% were over 50 years old, 58.3% were female, 68% were a low level of education, 74.8% were not working, 84.5% were diagnosed with diabetes for more than 5 years, 53.4% were using insulin therapy for more than 5 years, and only 65% had got formal training on medical sharp products disposal. Nearby 83.5% still recap the pen needle insulin with the inner needle cap after injecting insulin, and 92.2% still threw medical sharps on the street when traveling outside. Approximately 81.6% of respondents stored their unused needles and lancets in a secured manner that was inaccessible to children. The practice score for proper medical sharps disposal increased from 4.5 to 6.0 as a result of formal training provided by healthcare professionals, as determined by the Mann Whitney Test (p=0.001). Conclusions Formal training by healthcare workers was the only factor that improved medical sharps disposal practice among diabetic patients using insulin therapy.