bluuebunny/crossref_metadata_2025 huggingface dataset:
Early educational trajectories of children with autism spectrum disorder in Chile: challenges and facilitators
Authors: Martinez Camila , Davidoff Alexandra , Briceño Rocío
Published: October 2023

Inclusive education and special education are the means of education for people with special educational needs and specific disabilities. Inclusive education has been promoted in recent decades as the optimal method of educating in diversity. However, in Chile, access to quality education remains a major challenge for students and their families. In this article, we explore the experiences, motivations, and main factors in making early educational decisions by families and caregivers of children on the autism spectrum. In particular, using six semi-structured interviews conducted with families and caregivers of children, we study the process of initial entry into the educational system, including parents’ perceptions and knowledge of the access routes to it and the facilitators and barriers present for their incorporation. The results indicate that, from the very beginning, the information available social and family attitudes, may hinder children’s access to the available care and education system, with a generalized demand to strengthen social and institutional support networks. In general, and as may be expected, educational decisions, trajectories, and expectations are interdependent and evolve with the experience of caregivers and children in the educational system and their families.
Bariatric surgery and calcifediol treatment, Gordian knot of severe-obesity-related comorbidities treatment
Authors: Herrera-Martínez Aura D. , Castillo-Peinado Laura L. S. , Molina-Puerta María J. , Calañas-Continente Alfonso , Membrives Antonio , Castilla Juan , Camacho Cardenosa Marta , Casado-Díaz Antonio , Gálvez-Moreno María A. , Gahete Manuel D. , Quesada Gómez José Manuel , Bouillon Roger , Priego-Capote Feliciano , Luque Raúl M.
Published: October 2023

Background

Obesity (OB) is a chronic metabolic disease with important associated comorbidities and mortality. Vitamin D supplementation is frequently administered after bariatric surgery (BS), so as to reduce OB-related complications, maybe including chronic inflammation.

Aim

This study aimed to explore relations between vitamin D metabolites and components of the inflammasome machinery in OB before and after BS and their relations with the improvement of metabolic comorbidities.

Patients and methods

Epidemiological/clinical/anthropometric/biochemical evaluation was performed in patients with OB at baseline and 6 months after BS. Evaluation of i) vitamin-D metabolites in plasma and ii) components of the inflammasome machinery and inflammatory-associated factors [NOD-like-receptors (NLRs), inflammasome-activation-components, cytokines and inflammation/apoptosis-related components, and cell-cycle and DNA-damage regulators] in peripheral blood mononuclear cells (PBMCs) was performed at baseline and 6 months after BS. Clinical and molecular correlations/associations were analyzed.

Results

Significant correlations between vitamin D metabolites and inflammasome-machinery components were observed at baseline, and these correlations were significantly reduced 6 months after BS in parallel to a decrease in inflammation markers, fat mass, and body weight. Treatment with calcifediol remarkably increased 25OHD levels, despite 24,25(OH)2D3 remained stable after BS. Several inflammasome-machinery components were associated with improvement in metabolic comorbidities, especially hypertension and dyslipidemia.

Conclusion

The beneficial effects of vitamin D on OB-related comorbidities after BS patients are associated with significant changes in the molecular expression of key inflammasome-machinery components. The expression profile of these inflammasome components can be dynamically modulated in PBMCs after BS and vitamin D supplementation, suggesting that this profile could likely serve as a sensor and early predictor of the reversal of OB-related complications after BS.
Bibliometric analysis of rheumatic immune related adverse events associated with immune checkpoint inhibitors
Authors: Zeng Li , Ma Gang , Chen Kai , Zhou Qiao
Published: October 2023

Background

Immune checkpoint inhibitors (ICIs) has emerged as a popular cancer treatment approach. However, non-specific activation of T cells by ICIs can lead to immune-related adverse events (irAEs), including specific rheumatic manifestations. The study aimed to explore the current trend of ICIs associated rheumatic irAEs and summarize the knowledge structure through bibliometric methods.

Methods

The Web of Science Core Collection database (WoSCC) was selected for retrieving literature on ICIs associated rheumatic irAEs. To evaluate contributions from different countries/regions, institutions, journals, and authors, bibliometric analysis software, including VOSviewer and CiteSpace, as well as bibliometric online platforms, were utilized to construct and visualize bibliometric networks. Through the systematic review of this knowledge domain, future research directions were determined.

Results

In This study, a total of 803 publications on ICIs-associated rheumatic irAEs were included for analysis. The distribution of these publications revealed two distinct growth phases: a stable phase between 2007 to 2015 followed by rapid growth from 2016 to 2020. The United States emerged as the top contributor in terms of publications, citations, and h-index, with the majority of leading institutions and funding agencies located there. Apart from government funding, pharmaceutical companies such as Bristol Myers Squibb and Merck Company also play a significant role in drug development and research. Analysis of keywords and citation bursts indicated that the initial burst was related to “monoclonal antibody,” “anti-CLTA4 antibody,” and “melanoma”. This was followed by a rise in interest related to “sarcoidosis,” “safety,” “inflammatory arthritis,” and “preexisting autoimmune.”

Conclusion

This study summarized the global research trends concerning ICIs associated rheumatic irAEs. The findings can provide valuable insights into the current understanding of rheumatic irAEs, highlight the research trend and developments in the field. Future efforts should focus on developing classification criteria and guidelines, conducting prospective studies, investigating the mechanisms involved, and identifying biomarkers for prediction and monitoring of these events.
Age- and sex-specific differences in immune responses to BNT162b2 COVID-19 and live-attenuated influenza vaccines in UK adolescents
Authors: Jay Cecilia , Adland Emily , Csala Anna , Lim Nicholas , Longet Stephanie , Ogbe Ane , Ratcliff Jeremy , Sampson Oliver , Thompson Craig P. , Turtle Lance , Barnes Eleanor , Dunachie Susanna , Klenerman Paul , Carroll Miles , Goulder Philip
Published: October 2023

Introduction

The key to understanding the COVID-19 correlates of protection is assessing vaccine-induced immunity in different demographic groups. Young people are at a lower risk of COVID-19 mortality, females are at a lower risk than males, and females often generate stronger immune responses to vaccination.

Methods

We studied immune responses to two doses of BNT162b2 Pfizer COVID-19 vaccine in an adolescent cohort (n = 34, ages 12–16), an age group previously shown to elicit significantly greater immune responses to the same vaccine than young adults. Adolescents were studied with the aim of comparing their response to BNT162b2 to that of adults; and to assess the impacts of other factors such as sex, ongoing SARS–CoV–2 infection in schools, and prior exposure to endemic coronaviruses that circulate at high levels in young people. At the same time, we were able to evaluate immune responses to the co-administered live attenuated influenza vaccine. Blood samples from 34 adolescents taken before and after vaccination with COVID-19 and influenza vaccines were assayed for SARS–CoV–2-specific IgG and neutralising antibodies and cellular immunity specific for SARS–CoV–2 and endemic betacoronaviruses. The IgG targeting influenza lineages contained in the influenza vaccine were also assessed.

Results

Robust neutralising responses were identified in previously infected adolescents after one dose, and two doses were required in infection-naïve adolescents. As previously demonstrated, total IgG responses to SARS–CoV-2 Spike were significantly higher among vaccinated adolescents than among adults (aged 32–52) who received the BNT162b2 vaccine (comparing infection-naïve, 49,696 vs. 33,339; p = 0.03; comparing SARS-CoV–2 previously infected, 743,691 vs. 269,985; p <0.0001) by the MSD v-plex assay. There was no evidence of a stronger vaccine-induced immunity in females compared than in males.

Discussion

These findings may result from the introduction of novel mRNA vaccination platforms, generating patterns of immunity divergent from established trends and providing new insights into what might be protective following COVID-19 vaccination.
Metabolic regulation of forkhead box P3 alternative splicing isoforms and their impact on health and disease
Authors: Luo Zhidan , Zhang Yihua , Saleh Qais Waleed , Zhang Jie , Zhu Zhiming , Tepel Martin
Published: October 2023

Forkhead Box P3 (FOXP3) is crucial for the development and suppressive function of human regulatory T cells (Tregs). There are two predominant FOXP3 splicing isoforms in healthy humans, the full-length isoform and the isoform lacking exon 2, with different functions and regulation mechanisms. FOXP3 splicing isoforms show distinct abilities in the cofactor interaction and the nuclear translocation, resulting in different effects on the differentiation, cytokine secretion, suppressive function, linage stability, and environmental adaptation of Tregs. The balance of FOXP3 splicing isoforms is related to autoimmune diseases, inflammatory diseases, and cancers. In response to environmental challenges, FOXP3 transcription and splicing can be finely regulated by T cell antigen receptor stimulation, glycolysis, fatty acid oxidation, and reactive oxygen species, with various signaling pathways involved. Strategies targeting energy metabolism and FOXP3 splicing isoforms in Tregs may provide potential new approaches for the treatment of autoimmune diseases, inflammatory diseases, and cancers. In this review, we summarize recent discoveries about the FOXP3 splicing isoforms and address the metabolic regulation and specific functions of FOXP3 splicing isoforms in Tregs.
Multiobjective optimization of dimension and position of elliptical crush initiator on crashworthiness performance of square tube using response surface methodology
Authors: Hafid M. , Istiyanto Jos , Nasruddin Nasruddin
Published: October 2023

In this study, the crashworthiness performance of a thin-walled square steel-tube structure with an elliptical crush initiator under impact loading was investigated. The effect of the height, width, and distance of the crush initiator from the top of the tube on the crashworthiness performance was analyzed using several numerical simulations using ABAQUS Explicit. The response surface methodology was used to predict the crashworthiness performance indices, and optimization was performed to determine the optimal dimensions and position of the crush initiator. The optimization was aimed at minimizing the peak force (PF) while maximizing the mean crushing force (MCF), crush force efficiency (CFE), and specific energy absorption (SEA). The result was an elliptical crush initiator with a height of 15 mm, width of 24.784 mm, and distance of 15.08 mm. Validation was performed to verify these results. The optimal crush initiator effect resulted in a 10.12% decrease in the peak force, 13.67% increase in the crush force efficiency, and 2.23% increase in the mean crushing force. However, a slight decrease of 0.82% in specific energy absorption was observed.
A cross-sectional study confirms temporary post-COVID-19 vaccine menstrual irregularity and the associated physiological changes among vaccinated women in Jordan
Authors: Almomani Ensaf Y. , Hajjo Rima , Qablan Ahmad , Sabbah Dima A. , Al-Momany Abass
Published: October 2023

Background

COVID-19 vaccines continue to save people’s lives around the world; however, some vaccine adverse events have been a major concern which slowed down vaccination campaigns. Anecdotal evidence pointed to the vaccine effect on menstruation but evidence from the adverse event reporting systems and the biomedical literature was lacking. This study aimed to investigate the physiological changes in women during menstruation amid the COVID-19 vaccination.

Methods

A cross-sectional online survey was distributed to COVID-19 vaccinated women from Nov 2021 to Jan 2022. The results were analyzed using the SPSS software.

Results

Among the 564 vaccinated women, 52% experienced significant menstrual irregularities post-vaccination compared to before regardless of the vaccine type. The kind of menstrual irregularity varied among the vaccinated women, for example, 33% had earlier menstruation, while 35% reported delayed menstruation. About 31% experienced heavier menstruation, whereas 24% had lighter menstrual flow. About 29% had menstruation last longer, but 13% had it shorter than usual. Noteworthy, the menstrual irregularities were more frequent after the second vaccine shot, and they disappeared within 3 months on average. Interestingly, 24% of the vaccinated women reported these irregularities to their gynecologist.

Conclusion

The COVID-19 vaccine may cause physiological disturbances during menstruation. Luckily, these irregularities were short-termed and should not be a reason for vaccine hesitancy in women. Further studies are encouraged to unravel the COVID-19 vaccine adverse effect on women’s health.
HMGN2 and Histone H1.2: potential targets of a novel probiotic mixture for seasonal allergic rhinitis
Authors: Li Lisha , Wen Xueyi , Gong Yiyi , Chen Yuling , Xu Jiatong , Sun Jinlyu , Deng Haiteng , Guan Kai
Published: October 2023

Background

Allergic rhinitis (AR) is a common nasal inflammatory disorder that severely affects an individual's quality of life (QoL) and poses a heavy financial burden. In addition to routine treatments, probiotic intervention has emerged as a promising strategy for preventing and alleviating allergic diseases. The main objective of this study was to determine the effect of a novel multi-strain probiotic mixture on AR symptoms and investigate potential targets underlying the probiotic intervention.

Methods

A randomized, double-blind, placebo-controlled clinical study was conducted on AR patients who were allergic to autumnal pollens (n = 31). Placebo or a novel probiotic mixture, composed of Lactobacillus rhamnosus (L. rhamnosus) HN001, L. acidophilus NCFM, Bifidobacterium lactis (B. lactis) Bi-07, L. paracasei LPC-37, and L. reuteri LE16, was administered after 2 months. The therapeutic efficacy was evaluated by a symptom assessment scale. Before and during the pollen season, blood samples were collected, and peripheral blood mononuclear cells (PBMCs) were isolated for further tandem mass tags (TMTs)-based quantitative proteomic analyses. Potential targets and underlying pathological pathways were explored using bioinformatics methods.

Results

During the pollen season, the rhinoconjunctivitis symptom score of participants who were administered probiotics (probiotic group, n = 15) was significantly lower than those administered placebo (placebo group, n = 15) (P = 0.037). The proteomic analyses identified 60 differentially expressed proteins (DEPs) in the placebo group, and subsequent enrichment analyses enriched a series of pathways and biological processes, including signaling pathways of inflammation, coagulation cascade, lipid, carbohydrate and amino acid metabolic pathways, and transcription and translation processes. Least Absolute Shrinkage and Selection Operator (LASSO) regression extracted five main elements, namely, GSTO1, ATP2A2, MCM7, PROS1, and TRIM58, as signature proteins. A total of 17 DEPs were identified in the probiotic group, and there was no pathway enriched. Comparison of DEPs in the two groups revealed that the expression levels of the high-mobility group nucleosome-binding domain-containing protein 2 (HMGN2) and Histone H1.2 presented an opposite trend with different interventions.

Conclusion

Our data showed that AR symptoms alleviated after treatment with the novel multi-strain probiotic mixture, and the proteomic analyses suggested that HMGN2 and Histone H1.2 might be targets of probiotic intervention for seasonal AR.
Hyposalivation but not Sjögren’s syndrome associated with microbial dysbiosis in women
Authors: Saúco Carlos , Rus Maria J. , Nieto María R. , Barros Carolina , Cantiga-Silva Cristiane , Lendines-Cordero Débora , Calderer-Ortiz Marta , Zurita-García Miriam , Arias-Herrera Santiago , Monsalve-Guil Loreto , Segura-Egea Juan José , Simon-Soro Aurea
Published: October 2023

Background

Saliva modulates the environment of the oral biofilm through pH buffer, microbial attachment to host surfaces, and nutritional source. The ecology of stress occurs when a physical factor adversely impacts an ecosystem or its biotic components. Therefore, reduced salivary flow can affect oral-host balance. The leading causes of hyposalivation include disease-associated Sjögren’s syndrome (SS) and menopausal women as aging-associated. However, little is known about the oral microbiome integrated with sex hormones in hyposalivation. This study aimed to characterize the hyposalivation microbiome caused by aging or disease affecting the salivary glands in women.

Methods

We included 50 women older than 40 years of age in any menopausal phase. We collected stimulated saliva from 25 women diagnosed with SS (SS) and 25 without SS (non-SS). The bacterial profile of the patients was obtained by 16S rRNA sequencing. Bioinformatics analysis used machine learning to analyze the cohort’s signs, symptoms, and bacterial profile. Salivary estradiol as a sex hormone variation level was determined.

Results

We obtained that 79% of the SS group, and 52% of the non-SS group had hyposalivation. We found a negatively correlated Prevotella-age and Rothia-estradiol in the SS group. Highlight, we found that the cause of the hyposalivation in the study did not explain differences in microbial diversity comparing non-SS and SS groups. Therefore, microbial communities found in hyposalivation but not related to systemic conditions suggest that changes in the oral environment might underpin host-microbial balance.

Conclusion

The salivary microbiome was similar in women with and without SS. However, hyposalivation showed two distinctive clusters associated with the bacterial population profiles. Our study suggests that local ecological disturbances could drive the change in the microbiome.
A comprehensive review of the applications of bacteriophage-derived endolysins for foodborne bacterial pathogens and food safety: recent advances, challenges, and future perspective
Authors: Khan Fazal Mehmood , Chen Jie-Hua , Zhang Rui , Liu Bin
Published: October 2023

Foodborne diseases are caused by food contaminated by pathogenic bacteria such as Escherichia coli, Salmonella, Staphylococcus aureus, Listeria monocytogenes, Campylobacter, and Clostridium, a critical threat to human health. As a novel antibacterial agent against foodborne pathogens, endolysins are peptidoglycan hydrolases encoded by bacteriophages that lyse bacterial cells by targeting their cell wall, notably in Gram-positive bacteria due to their naturally exposed peptidoglycan layer. These lytic enzymes have gained scientists’ interest in recent years due to their selectivity, mode of action, engineering potential, and lack of resistance mechanisms. The use of endolysins for food safety has undergone significant improvements, which are summarized and discussed in this review. Endolysins can remove bacterial biofilms of foodborne pathogens and their cell wall-binding domain can be employed as a tool for quick detection of foodborne pathogens. We explained the applications of endolysin for eliminating pathogenic bacteria in livestock and various food matrices, as well as the limitations and challenges in use as a dietary supplement. We also highlight the novel techniques of the development of engineering endolysin for targeting Gram-negative bacterial pathogens. In conclusion, endolysin is safe and effective against foodborne pathogens and has no adverse effect on human cells and beneficial microbiota. As a result, endolysin could be employed as a functional bio-preservative agent to improve food stability and safety and maintain the natural taste of food quality.
The multidrug-resistant Pseudomonas fluorescens strain: a hidden threat in boar semen preservation
Authors: Xiong Zhixuan , Hong Ziqiang , Li Xinxin , Gao Dongyang , Wang Linkang , Liu Shudan , Zhao Junna , Li Xiangmin , Qian Ping
Published: October 2023

Although the bacterial composition of boar ejaculate has been extensively studied, the bacterial composition of extended boar semen is often overlooked, despite the potential risks these microorganisms may pose to the long-term preservation of extended boar semen at 15–17°C. In this study, we characterized the bacterial community composition of extended semen and discovered that Pseudomonas spp. was the dominant flora. The dominant strains were further isolated and identified as a potential new species in the Pseudomonas fluorescens group and named GXZC strain, which had adverse effects on sperm quality and was better adapted to growth at 17°C. Antimicrobial susceptibility testing showed that the GXZC strain was resistant to all commonly used veterinary antibiotics. Whole-genome sequencing (WGS) and genome annotation revealed the large genetic structure and function [7,253,751 base pairs and 6,790 coding sequences (CDSs)]. Comparative genomic analysis with the closest type strains showed that the GXZC strain predicted more diversity of intrinsic and acquired resistance genes to multi-antimicrobial agents. Taken together, our study highlights a problem associated with the long-term storage of extended boar semen caused by a P. fluorescens group strain with unique biological characteristics. It is essential to develop a new antibacterial solution for the long-term preservation of boar semen.
Cryo-electron microscopy in the fight against COVID-19—mechanism of virus entry
Authors: Bodakuntla Satish , Kuhn Christopher Cyrus , Biertümpfel Christian , Mizuno Naoko
Published: October 2023

Cryogenic electron microscopy (cryo-EM) and electron tomography (cryo-ET) have become a critical tool for studying viral particles. Cryo-EM has enhanced our understanding of viral assembly and replication processes at a molecular resolution. Meanwhile, in situ cryo-ET has been used to investigate how viruses attach to and invade host cells. These advances have significantly contributed to our knowledge of viral biology. Particularly, prompt elucidations of structures of the SARS-CoV-2 spike protein and its variants have directly impacted the development of vaccines and therapeutic measures. This review discusses the progress made by cryo-EM based technologies in comprehending the severe acute respiratory syndrome coronavirus-2 (SARS-Cov-2), the virus responsible for the devastating global COVID-19 pandemic in 2020 with focus on the SARS-CoV-2 spike protein and the mechanisms of the virus entry and replication.
Cardiolipin occupancy profiles of YidC paralogs reveal the significance of respective TM2 helix residues in determining paralog-specific phenotypes
Authors: Mishra Surabhi , van Aalst Evan J. , Wylie Benjamin J. , Brady L. Jeannine
Published: October 2023

YidC belongs to an evolutionarily conserved family of insertases, YidC/Oxa1/Alb3, in bacteria, mitochondria, and chloroplasts, respectively. Unlike Gram-negative bacteria, Gram-positives includingStreptococcus mutansharbor two paralogs of YidC. The mechanism for paralog-specific phenotypes of bacterial YidC1 versus YidC2 has been partially attributed to the differences in their cytoplasmic domains. However, we previously identified a W138R gain-of-function mutation in the YidC1 transmembrane helix 2. YidC1W138Rmostly phenocopied YidC2, yet the mechanism remained unknown. Primary sequence comparison of streptococcal YidCs led us to identify and mutate the YidC1W138analog, YidC2S152to W/A, which resulted in a loss of YidC2- and acquisition of YidC1-like phenotype. The predicted lipid-facing side chains of YidC1W138/YidC2S152led us to propose a role for membrane phospholipids in specific-residue dependent phenotypes ofS. mutansYidC paralogs. Cardiolipin (CL), a prevalent phospholipid in theS. mutanscytoplasmic membrane during acid stress, is encoded by a single gene,cls. We show a concerted mechanism for cardiolipin and YidC2 under acid stress based on similarly increased promoter activities and similar elimination phenotypes. Using coarse grain molecular dynamics simulations with the Martini2.2 Forcefield, YidC1 and YidC2 wild-type and mutant interactions with CL were assessedin silico. We observed substantially increased CL interaction in dimeric versus monomeric proteins, and variable CL occupancy in YidC1 and YidC2 mutant constructs that mimicked characteristics of the other wild-type paralog. Hence, paralog-specific amino acid- CL interactions contribute to YidC1 and YidC2-associated phenotypes that can be exchanged by point mutation at positions 138 or 152, respectively.
System-level biological effects of extremely low-frequency electromagnetic fields: an in vivo experimental review
Authors: Tian Haoyang , Zhu Haozheng , Gao Chenhao , Shi Mingxia , Yang Dekun , Jin Mingyu , Wang Fenghua , Sui Xiaohong
Published: October 2023

During the past decades, the potential effects of extremely low-frequency electromagnetic fields (ELF-EMFs) on human health have gained great interest all around the world. Though the International Commission on Non-Ionizing Radiation Protection recommended a 100 μT, and then a 200 μT magnetic field limit, the long-term effects of ELF-EMFs on organisms and systems need to be further investigated. It was reported that both electrotherapy and possible effects on human health could be induced under ELF-EM radiation with varied EM frequencies and fields. This present article intends to systematically review the in vivo experimental outcome and the corresponding mechanisms to shed some light on the safety considerations of ELF-EMFs. This will further advance the subsequent application of electrotherapy in human health.
Germline landscape of RPA1, RPA2 and RPA3 variants in pediatric malignancies: identification of RPA1 as a novel cancer predisposition candidate gene
Authors: Sharma Richa , Oak Ninad , Chen Wenan , Gogal Rose , Kirschner Martin , Beier Fabian , Schnieders Michael J. , Spies Maria , Nichols Kim E. , Wlodarski Marcin
Published: October 2023

Replication Protein A (RPA) is single-strand DNA binding protein that plays a key role in the replication and repair of DNA. RPA is a heterotrimer made of 3 subunits – RPA1, RPA2, and RPA3. Germline pathogenic variants affecting RPA1 were recently described in patients with Telomere Biology Disorders (TBD), also known as dyskeratosis congenita or short telomere syndrome. Premature telomere shortening is a hallmark of TBD and results in bone marrow failure and predisposition to hematologic malignancies. Building on the finding that somatic mutations in RPA subunit genes occur in ~1% of cancers, we hypothesized that germline RPA alterations might be enriched in human cancers. Because germline RPA1 mutations are linked to early onset TBD with predisposition to myelodysplastic syndromes, we interrogated pediatric cancer cohorts to define the prevalence and spectrum of rare/novel and putative damaging germline RPA1, RPA2, and RPA3 variants. In this study of 5,993 children with cancer, 75 (1.25%) harbored heterozygous rare (non-cancer population allele frequency (AF) < 0.1%) variants in the RPA heterotrimer genes, of which 51 cases (0.85%) had ultra-rare (AF < 0.005%) or novel variants. Compared with Genome Aggregation Database (gnomAD) non-cancer controls, there was significant enrichment of ultra-rare and novel RPA1, but not RPA2 or RPA3, germline variants in our cohort (adjusted p-value < 0.05). Taken together, these findings suggest that germline putative damaging variants affecting RPA1 are found in excess in children with cancer, warranting further investigation into the functional role of these variants in oncogenesis.
Cohort profile: the Turin prostate cancer prognostication (TPCP) cohort
Authors: Destefanis Nicolas , Fiano Valentina , Milani Lorenzo , Vasapolli Paolo , Fiorentino Michelangelo , Giunchi Francesca , Lianas Luca , Del Rio Mauro , Frexia Francesca , Pireddu Luca , Molinaro Luca , Cassoni Paola , Papotti Mauro Giulio , Gontero Paolo , Calleris Giorgio , Oderda Marco , Ricardi Umberto , Iorio Giuseppe Carlo , Fariselli Piero , Isaevska Elena , Akre Olof , Zelic Renata , Pettersson Andreas , Zugna Daniela , Richiardi Lorenzo
Published: October 2023

Introduction

Prostate cancer (PCa) is the most frequent tumor among men in Europe and has both indolent and aggressive forms. There are several treatment options, the choice of which depends on multiple factors. To further improve current prognostication models, we established the Turin Prostate Cancer Prognostication (TPCP) cohort, an Italian retrospective biopsy cohort of patients with PCa and long-term follow-up. This work presents this new cohort with its main characteristics and the distributions of some of its core variables, along with its potential contributions to PCa research.

Methods

The TPCP cohort includes consecutive non-metastatic patients with first positive biopsy for PCa performed between 2008 and 2013 at the main hospital in Turin, Italy. The follow-up ended on December 31st 2021. The primary outcome is the occurrence of metastasis; death from PCa and overall mortality are the secondary outcomes. In addition to numerous clinical variables, the study’s prognostic variables include histopathologic information assigned by a centralized uropathology review using a digital pathology software system specialized for the study of PCa, tumor DNA methylation in candidate genes, and features extracted from digitized slide images via Deep Neural Networks.

Results

The cohort includes 891 patients followed-up for a median time of 10 years. During this period, 97 patients had progression to metastatic disease and 301 died; of these, 56 died from PCa. In total, 65.3% of the cohort has a Gleason score less than or equal to 3 + 4, and 44.5% has a clinical stage cT1. Consistent with previous studies, age and clinical stage at diagnosis are important prognostic factors: the crude cumulative incidence of metastatic disease during the 14-years of follow-up increases from 9.1% among patients younger than 64 to 16.2% for patients in the age group of 75-84, and from 6.1% for cT1 stage to 27.9% in cT3 stage.

Discussion

This study stands to be an important resource for updating existing prognostic models for PCa on an Italian cohort. In addition, the integrated collection of multi-modal data will allow development and/or validation of new models including new histopathological, digital, and molecular markers, with the goal of better directing clinical decisions to manage patients with PCa.
Efficacy and safety of olaparib combined with abiraterone in patients with metastatic castration-resistant prostate cancer: a systematic review and meta-analysis of randomized controlled trials
Authors: Luo Zhanyang , Zhu Bukun , Xu Hong , Chen Lixin , Song Xiaoyun , Wang Yu , Wang Rui , Zheng Jinzhou , Qiu Yunhua , Yang Jianfeng , Shi Youyang
Published: October 2023

Background

Olaparib has been proven for the treatment of metastatic castration-resistant prostate cancer (mCRPC). This meta-analysis aims to comprehensively evaluate the efficacy and safety of the combination of olaparib and abiraterone in patients with mCRPC.

Methods

The literature in PubMed, Embase, and Cochrane Library up until April 27, 2023, was systematically searched. In the studies included in this meta-analysis, olaparib combined with abiraterone was compared with abiraterone combined with placebo.

Results

Two randomized controlled trials involving a total of 938 patients were included. Analysis indicated that olaparib combined with abiraterone significantly prolonged radiographic progression-free survival (rPFS: relative risk [RR] 0.66, 95% confidence interval [CI] 0.55–0.79), time to secondary progression or death (PFS2: hazard ratio [HR] 0.72, 95% CI 0.56–0.93), time to first subsequent therapy or death (TFST: HR 0.75, 95% CI 0.63–0.89), time to second subsequent therapy or death (TSST: HR 0.73, 95% CI 0.58–0.93), and confirmed prostate-specific antigen (PSA) response (RR 1.14, 95% CI 1.05–1.24). However, no statistically significant differences were found in the overall survival (OS: HR 0.87 95% CI 0.70–1.09), objective response rate (ORR: RR 0.97, 95% CI 0.70–1.33), and incidence of total adverse events (RR 1.07, 95% CI 0.94–1.22). A notable detail that the combination of olaparib and abiraterone was associated with an increased incidence of high-grade anemia (RR 7.47, 95% CI 1.36–40.88).

Conclusion

Olaparib combined with abiraterone is effective for patients with mCRPC. However, combination therapy has treatment-related adverse events compared with monotherapy, and this could be improved in future treatment management.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023432287.
Case report: Chronic pain in a pediatric patient with late-onset pompe disease
Authors: Cao Amanda , van Gool Raquel , Golden Emma , Goodlett Benjamin , Camelo Carlos , Bujoreanu Simona , Al-Hertani Walla , Upadhyay Jaymin
Published: October 2023

Pompe disease (PD) is a rare inherited metabolic disorder of deficient or absent acid alpha-glucosidase (GAA), resulting in defective lysosomal glycogen catabolism. Muscle weakness, respiratory deficiency and gastrointestinal symptoms are commonly monitored in PD. However, pain and associated psychological symptoms are less focused upon. A pediatric patient with late-onset Pompe disease (LOPD) comorbid with chronic pain is presented. Symptoms of pain in the feet were first reported between 6 and 7 years of age and were attributed to growing pains. Following progression of lower body pain, weakness, fatigue, and difficulties with ambulation, a thorough clinical assessment including genetic testing was performed, which led to a diagnosis of LOPD at 9 years of age. ERT with recombinant human alglucosidase alfa was subsequently started. The patient’s clinical status is compounded by depressed mood, anxiety, and attention deficit hyperactivity disorder, which may further exacerbate pain. A multidisciplinary pain treatment approach consisting of orthopedics, physical therapy, and psychosocial therapy aimed at enhancing pain coping skills is described for this LOPD patient. This case highlights the need for a greater understanding of pain generation and identification of optimized pain treatment approaches in children with LOPD that can be implemented alongside ERT.
A systematic review of clinical practice guidelines and recommendations for the management of pain, sedation, delirium and iatrogenic withdrawal syndrome in pediatric intensive care
Authors: MacDonald Ibo , Alvarado Silvia , Marston Mark T. , Gomez Tovar Luz , Chanez Vivianne , Favre Eva , Gu Ying , Trombert Alexia , Perez Maria-Helena , Ramelet Anne-Sylvie
Published: October 2023

Introduction

This systematic review aimed to evaluate the quality of clinical practice guidelines (CPGs) and recommendations for managing pain, sedation, delirium, and iatrogenic withdrawal syndrome in pediatric intensive care (PICU). The objectives included evaluating the quality of recommendations, synthesizing recommendations, harmonizing the strength of the recommendation (SoR) and the certainty of evidence (CoE), and assessing the relevance of supporting evidence.

Methods

A comprehensive search in four electronic databases (Medline, Embase.com, CINAHL and JBI EBP Database), 9 guideline repositories, and 13 professional societies was conducted to identify CPGs published from January 2010 to the end of May 2023 in any language. The quality of CPGs and recommendations was assessed using the AGREE II and AGREE-REX instruments. Thematic analysis was used to synthesize recommendations, and the GRADE SoR and CoE harmonization method was used to interpret the credibility of summary recommendations.

Results

A total of 18 CPGs and 170 recommendations were identified. Most CPGs were of medium-quality, and three were classified as high. A total of 30 summary recommendations were synthesized across each condition, focused on common management approaches. There was inconsistency in the SoRs and CoE for summary recommendations, those for assessment showed the highest consistency, the remaining were conditional, inconsistent, inconclusive, and lacked support from evidence.

Conclusion

This systematic review provides an overview of the quality of CPGs for these four conditions in the PICU. While three CPGs achieved high-quality ratings, the overall findings reveal gaps in the evidence base of recommendations, patient and family involvement, and resources for implementation. The findings highlight the need for more rigorous and evidence-based approaches in the development and reporting of CPGs to enhance their trustworthiness. Further research is necessary to enhance the quality of recommendations for this setting. The results of this review can provide a valuable foundation for future CPG development.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=274364, PROSPERO (CRD42021274364).
Real-world study of the leakage of two types of infusion bags in multicenter pharmacy intravenous admixture service (PIVAS)
Authors: Yin Yanchao , Fu Wei , Liu Wenhua , Li Feie , Gong Xuepeng , Liu Dong , Li Juan
Published: October 2023

Background: This study sought to analyze the leakage rate, economic loss caused by leakage, leakage reasons, and usage of upright polypropylene infusion bags and non-polyvinyl chloride (PVC) infusion bags, two types of closed intravenous infusion containers used in pharmacy intravenous admixture service (PIVAS), to improve the product quality of drug infusion packaging materials, reduce drug and clinical economic losses, and reduce the safety hazards of medication.

Method: A real-world study was used to collect statistics for these infusion containers. The study was conducted in 21 hospitals in China from September to December 2022. Upright polypropylene infusion bags or non-PVC infusion bags in PIVAS of these 21 hospitals were chosen as the research material.

Results: In total, 2,349,899 upright polypropylene infusion bags and 3,301,722 non-PVC infusion bags were collected. Eleven cases of upright polypropylene infusion bag leakage occurred (with a the leakage rate of 0.05‱), and 394 cases of non-PVC infusion bag leakage occurred (with a leakage rate of 1.19‱). The leakage rate of non-PVC infusion bags was significantly higher than that of upright polypropylene infusion bags (p < 0.01). The main reason for leakage in upright polypropylene infusion bags was sharp objects such as glass fragments or aluminum caps piercing the bag. The main reason for leakage in non-PVC infusion bags was squeezing, stacking, and uneven arrangement that causes folding of edges. For non-PVC bags, additional reasons for leakage included leakage at the nozzle joint, excessive manual or machine throwing force, and excessive dosage. The economic loss of upright polypropylene infusion bags was 1,116.56 CNY. The economic loss of non-PVC infusion bags was 32,210.86 CNY.

Conclusion: Based on real-world study data on the leakage of upright polypropylene infusion bags and non-PVC infusion bags in multicenter PIVAS, it can be concluded that the leakage rates of upright polypropylene infusion bags are significantly lower than those of non-PVC infusion bags in PIVAS, and the economic losses due to upright polypropylene infusion bags are lower than those due to non-PVC infusion bags in PIVAS. Therefore, we can infer that upright polypropylene infusion bags are superior to non-PVC infusion bags.
Cardiorenal ketone metabolism: a positron emission tomography study in healthy humans
Authors: Cuenoud Bernard , Croteau Etienne , St-Pierre Valérie , Richard Gabriel , Fortier Mélanie , Vandenberghe Camille , Carpentier André C. , Cunnane Stephen C.
Published: October 2023

Ketones are alternative energy substrates for the heart and kidney but no studies have investigated their metabolism simultaneously in both organs in humans. The present double tracer positron emission tomography (PET) study evaluated the organ distribution and basal kinetic rates of the radiolabeled ketone, 11C-acetoacetate (11C-AcAc), in the heart and kidney compared to 11C-acetate (11C-Ac), which is a well-validated metabolic radiotracer. Both tracers were highly metabolized by the left ventricle and the renal cortex. In the heart, kinetic rates were similar for both tracers. But in the renal cortex, uptake of 11C-Ac was higher compared to 11C-AcAc, while the reverse was observed for the clearance. Interestingly, infusion of 11C-AcAc led to a significantly delayed release of radioactivity in the renal medulla and pelvis, a phenomenon not observed with 11C-Ac. This suggests an equilibrium of 11C-AcAc with the other ketone, 11C-D-beta-hydroxybutyrate, and a different clearance profile. Overall, this suggests that in the kidney, the absorption and metabolism of 11C-AcAc is different compared to 11C-Ac. This dual tracer PET protocol provides the opportunity to explore the relative importance of ketone metabolism in cardiac and renal diseases, and to improve our mechanistic understanding of new metabolic interventions targeting these two organs.
Exploring friendship quality and the practice of savoring in relation to the wellbeing of Greek adults
Authors: Pezirkianidis Christos , Christopoulou Maria , Galanaki Evangelia , Kounenou Kalliope , Karakasidou Eirini , Lekka Dimitra , Kalamatianos Antonios , Stalikas Anastassios
Published: October 2023

Previous research findings demonstrate that both savoring ability and the presence of high-quality friendships play a significant role in enhancing one’s overall sense of wellbeing. However, these associations have not been thoroughly investigated within a diverse range of adults across their lifespans, nor have they been explored in the specific cultural context of Greece. Thus, the primary objective of this study was to delve into the relationships between close friendship quality, the utilization of savoring techniques, and wellbeing within the Greek cultural framework. The study involved 771 adults from Greece with an average age of 38.35 years, who completed the McGill Friendship Functions Questionnaire, the PERMA Profiler, and the Abridged Ways of Savoring Checklist. Results revealed that there exists a positive correlation between friendship quality and savoring strategies with overall wellbeing. Moreover, the study identified a significant association wherein a greater employment of savoring strategies was linked to higher levels of friendship quality. While this study contributes valuable insights, it also has limitations that warrant acknowledgment. Furthermore, suggestions for potential future research directions are proposed, and the implications of these findings are discussed in relation to interventions aimed at enhancing both friendships and the practice of savoring across various contexts.
Exploring the experience of meaning-centered group psychotherapy among Chinese cancer patients during active treatment: a descriptive qualitative study
Authors: Wang Shuman , Zheng Mimi , Zhu Yu , Zhang Lijuan , Li Xiaoru , Wan Hongwei
Published: October 2023

Objective

Meaninglessness poses a significant psychological challenge for cancer patients, negatively affecting their quality of life and increasing the risk of suicide. Meaning-Centered Group Therapy (MCGP) is an intervention designed specifically to enhance the meaning of life of cancer patients. Extensive research has documented its effectiveness across various cultures and populations. However, limited research has been conducted on the subjective experiences and perspectives of participants engaged in MCGP. Thus, the purpose of this study was to employ a qualitative design to explore the experiences and viewpoints of Chinese cancer patients who have undergone MCGP.

Methods

Within a two-week timeframe following the conclusion of MCGP, semi-structured interviews were administered to twenty-one participants who had engaged in the therapy. The interview data were transcribed and subjected to thematic analysis.

Results

Four main themes were identified: (a) Self-perceived personal change, (b) Overall experience of group therapy, (c) Barriers to participation of MCGP, and (d) Suggestions for future interventions.

Conclusion

Despite the barriers to participation in the MCGP process, the overall experience for Chinese cancer patients undergoing active treatment is valuable and positive, providing multiple benefits. Future studies could explore the adaptation of MCGP to a broader range of cancer populations and diverse study populations.
The relationship between obesity associated weight-adjusted waist index and the prevalence of hypertension in US adults aged ≥60 years: a brief report
Authors: Wang Jiao , Yang Qing-Ye , Chai Dong-jian , Su Yue , Jin Qi-Zhi , Wang Jin-Hua
Published: October 2023

Objectives

The main objective was to examine the relationship between weight-adjusted waist index (WWI) and the prevalence of hypertension among individuals aged ≥60 years who participated in the NHANES between 2011 and 2018 years.

Methods

The data for this study were obtained from the National Health and Nutrition Examination Survey (NHANES) 2011–2018. In this population-based study, we focused on participants who were over 60 years old. Data were collected from the aforementioned survey, and the variable of interest was WWI, which was calculated as waist (cm) divided by the square root of body weight (kg). Multivariable logistic regression model was applied to calculate adjusted ORs with 95% CIs in order to explore any possible correlation between WWI and the prevalence of hypertension. Subgroup analysis were used to verify the stability of the relationship between WWI and the prevalence of hypertension. The interaction tests were also conducted in this research.

Results

Results revealed that adults aged ≥60 years who were in the highest WWI quartile had significantly higher chances of developing hypertension when compared to those in the lowest quartile, after adjusting for covariates and potential confounders (p < 0.001).

Conclusion

These findings suggest that there is a strong correlation between elevated levels of WWI and the risk of developing hypertension among older adults. As such, WWI could serve as a unique and valuable biomarker for identifying hypertension risk at an earlier stage in the older adults population.