bluuebunny/crossref_metadata_2025 huggingface dataset:
Cryptosporidium species and subtypes identified in human domestic cases through the national microbiological surveillance programme in Sweden from 2018 to 2022
Authors: Bujila Ioana , Troell Karin , Ögren Jessica , Hansen Anette , Killander Gustav , Agudelo Lady , Lebbad Marianne , Beser Jessica
Published: January 2024

Background

The intestinal protozoan parasite Cryptosporidium is an important cause of diarrheal disease worldwide. A national microbiological surveillance programme was implemented in Sweden in 2018 in order to increase knowledge of the molecular epidemiology of human cryptosporidiosis to better understand transmission patterns and potential zoonotic sources. This article summarises the results of the first five years of the surveillance programme.

Methods

Cryptosporidium-positive faecal and DNA samples from domestically acquired infections were collected from clinical microbiological laboratories in Sweden. Species and subtype determination was performed using 60 kDa glycoprotein and/or small subunit ribosomal RNA gene analysis.

Results

Between 2018 and 2022, 1654 samples were analysed and 11 different species were identified: C. parvum (n = 1412), C. mortiferum (n = 59), C. hominis (n = 56), C. erinacei (n = 11), C. cuniculus (n = 5), C. meleagridis (n = 3), C. equi (n = 2), C. ubiquitum (n = 2), and one each of C. canis, C. ditrichi and C. felis. Subtyping revealed seven subtype families of C. parvum (new subtype families IIy and IIz) and 69 different subtypes (11 new subtypes). The most common C. parvum subtypes were IIdA22G1c, IIdA24G1, IIdA15G2R1 and IIaA16G1R1b. For C. hominis, four different subtype families and nine different subtypes (two new subtypes) were identified. For additional species, two new subtype families (IIIk and VId) and nine new subtypes were identified. All successfully subtyped C. mortiferum cases were subtype XIVaA20G2T1, confirming previous findings in Sweden. Several outbreaks were identified of which the majority were foodborne and a few were due to direct contact with infected animals.

Conclusion

Infection with C. parvum is the leading cause of human cryptosporidiosis acquired in Sweden, where more than 90% of domestic cases are caused by this zoonotic species and only a small proportion of cases are due to infection with other species. The rodent-associated C. mortiferum is considered an emerging zoonotic species in Sweden and the number of domestically acquired human cases has surpassed that of infection with C. hominis. A high diversity of species and subtypes, as well as diversity within the same subtype, was detected. Also, cryptosporidiosis appears to affect adults to a great extent in Sweden.
Assessment of the hematological profile of children with chronic kidney disease on follow-up at St. Paul’s Hospital Millennium Medical College and Tikur Anbessa Specialized Hospital in Addis Ababa, Ethiopia
Authors: Shenkut Melaku , Urgessa Fekadu , Alemu Rahel , Abebe Bezaye
Published: January 2024

Background

Chronic kidney disease (CKD) is a major public health issue with an increasing incidence and prevalence worldwide. In CKD, hematological parameters are influenced, and the effect increases with CKD stage. Thus, the aim of this study was to assess hematological profile of children with CKD on follow up at Tikur Anbessa Specialized Hospital and St. Paul’s Hospital Millennium Medical College in Addis Ababa, Ethiopia.

Methods

A cross-sectional study was carried out from March 1 to June 30, 2021 among 238 children with CKD. EDTA tubes were used to collect 4 ml blood samples, which were then examined by Beckman Coulter automated hematology analyzer. SPSS Version 20 was used for statistical analysis, and a bivariate and multivariate regression model were applied to assess correlations. Mean and standard deviation was used to determine hematological profiles.

Results

The total number of patients in the study were 238, with 42 (59.7%) of them being men. The majority of the patients (81%) had CKD stage 1. Mean ± standard deviation determined for white blood cell (WBC) parameters in (thousand/µL); WBC, Neutrophil, Lymphocytes, Eosinophil, Monocytes and Basophil were 8.93 ± 3.32, 4.6 ± 8.31, 2.79 ± 1.62, 0.31 ± 0.51, 0.50 ± 3.03 and 0.03 ± 0.24, respectively. For some of red blood cell (RBC) parameters; RBC (million/ µL), Hemoglobin (Hgb) (g/dL), Hematocrit (Hct) (%) and Mean cell volume (fl.) were 4.73 ± 0.87, 12.82 ± 2.76, 38.28 ± 7.53 and 80.32 ± 7.89, respectively. For the platelet count (PLT) (thousand/µL) and Mean Platelet volume (MPV) (fL) 349.34 ± 130.18 and 9.03 ± 4.31 were determined, respectively. This study also found hematologic parameters such as RBC, HGB, HCT and MPV were found to be positively correlated with eGFR with a P-value < 0.05 for all parameters.

Conclusion

The study found that the majority of study participants were in stages 1 to 3 based on their estimated glomerular filtration rate (eGFR). Some of hematological parameters found to have positive correlation with eGFR. There is a need to improve multiple aspects of CKD management, including routine hematological tests for children with chronic kidney disease.
Discontinuation risk from adverse events: immunotherapy alone vs. combined with chemotherapy: a systematic review and network meta-analysis
Authors: Shin Sangwon , Moon Jimin , Oum Chiyoon , Kim Seulki , Cho Soo Ick , Lim Yoojoo , Ock Chan-Young , Shin Seunghwan
Published: January 2024

Background

While immunotherapy combined with chemotherapy (Chemo-IO) is generally recognized for providing superior outcomes compared to monotherapy (mono-IO), it is associated with a higher incidence of treatment-related adverse events (TRAEs), which may lead to treatment discontinuation. In this study, we compared the rates of treatment discontinuation between mono-IO and Chemo-IO as first-line treatments for various solid tumors.

Methods

We systematically reviewed clinical trials from databases (PubMed, Embase, Cochrane Library, and an additional source) published from January 1, 2018, to July 10, 2023. We included phase III randomized controlled trials (RCTs) that utilized immunotherapy agents in at least one arm as first-line treatments for a variety of solid tumors. Data extraction followed the Preferred Reporting Items for Systematic Reviews (PRISMA) extension statement for network meta-analysis. A random effects model was used for the network meta-analysis, with the risk of bias assessed using the Cochrane risk-of-bias tool II. The primary outcomes encompassed treatment discontinuation rates due to TRAEs among patients who underwent immunotherapy, either alone or combined with chemotherapy, for various solid tumors. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated to compare between treatment groups.

Results

From 29 RCTs, a total of 21,677 patients and 5 types of treatment were analyzed. Compared to mono-IO, Chemo-IO showed a significantly higher rate of discontinuation due to TRAEs (RR 2.68, 95% CI 1.98–3.63). Subgroup analysis for non-small cell lung cancer (NSCLC) patients also exhibited a greater risk of discontinuation due to TRAEs with Chemo-IO compared to mono-IO (RR 2.93, 95% CI 1.67–5.14). Additional analyses evaluating discontinuation rates due to either treatment emergent adverse events (TEAEs) or AEs regardless of causality (any AEs) consistently revealed an elevated risk associated with Chemo-IO.

Conclusions

Chemo-IO was associated with an elevated risk of treatment discontinuation not only due to TRAEs but also any AEs or TEAEs. Given that the treatment duration can impact clinical outcomes, a subset of patients might benefit more from mono-IO than combination therapy. Further research is imperative to identify and characterize this subset.
Evaluation of the relationship of posterior tibial slope with gender and age in Turkish population with 3 different methods
Authors: Kavak Seyhmus , Kaya Sehmuz
Published: January 2024

Background

This study aimed to reveal the posterior tibial slope (PTS) angle with 3 different methods in a large case group in the Turkish population. In addition, the reproducibility of the measurement methods used was questioned while determining the age groups, gender and side relationship of this angle.

Materials and methods

In our retrospective study, radiographs of both knees were evaluated in all 610 patients (344 women, 56.4%) aged 25–65 years. PTS angles were measured by a radiologist and an orthopedist using anterior tibial cortex (ATC), posterior tibial cortex (PTC) and proximal tibial anatomical axis (PTAA) methods. The relationship of these angles with age group and gender, and the intra-class and inter-class correlations of all three methods were evaluated.

Results

The mean and standard deviation (SD) of PTS angle was 11.03 ± 2.33° with ATC method, 6.25 ± 2.22° with PTC and 8.68 ± 2.16° with PTAA, and the difference was significant (p < .001). In the evaluation according to age groups, the highest mean PTS angles were detected in cases aged 25–35 (9.63 ± 1.97° [mean ± SD] by PTAA method), and there was a significant difference in comparison with other age groups (p < .05). In comparison with age groups, higher mean PTS angles were found in women and on the right side, but the difference was not statistically significant (p > .05). The intraclass and interclass correlation coefficient (ICC) of all three methods was excellent (ICC > 0.91).

Conclusion

This study emphasizes that the mean PTS angle in Turkish population is higher than the angle values ​​recommended by prosthesis manufacturers, and factors such as patient age and gender should be calculated in order to ensure more effective prostheses to be applied to patients.
Meckel’s diverticulum mimicking acute appendicitis in children: a retrospective cohort study
Authors: Yan Ling , Zhou Bi , Wu Peng , Tian You , Lou Yi
Published: January 2024

Background

The aims of this study were to summarize the clinical presentation and histological results of 20 cases of complicated Meckel diverticulum (MD) who were presumed to have acute appendicitis before surgery, as well as to improve the diagnosis and treatment of complicated MD in children.

Materials and methods

We retrospectively reviewed the records of 20 complicated MD admitted to our institution who were preoperatively diagnosed with acute appendicitis from January 2012 to January 2019. Patients were divided into the perforated MD group and the Meckel’s diverticulitis group. Patient demographics, clinical manifestations, laboratory data, auxiliary examinations, surgical methods, and the result of heterotopic tissue were recorded.

Results

A total of 20 cases of complicated MD (perforated or diverticulitis) were identified. Children were aged from 3 to 13 years, with a mean age of 7.75 years (median 7.75; range, 1–13 years). Perforated Meckel’s diverticulum occurred in 5 of 20 (25%) cases. For perforated MD versus diverticulitis, no significant differences were found between age, time to intervention, length of hospital stay, and distance from the ileo-cecal valve. Heterotopic tissue was confirmed on histopathology in 75% of all patients, including 10 cases of gastric mucosa, 3 cases of coexistent gastric mucosa and pancreatic tissue, and 2 cases of pancreatic tissue. All patients underwent diverticulectomy or partial ileal resection under laparoscopy or laparotomy; two cases combined with appendectomy owing to slight inflammation of the appendix.

Conclusions

The most common presentation of symptomatic MD is painless rectal bleeding; however, it can present symptoms of acute abdomen mimicking acute appendicitis. The key point of diverticulectomy is to remove the ectopic mucosa completely.
Development of a mobile application to represent food intake in inpatients: dietary data systematization
Authors: Molter Alan Renier Jamal Occhioni , da Rocha Carvalho Naise Oliveira , Torres Paloma Ribeiro , da Silva Marlete Pereira , de Brito Patrícia Dias , do Brasil Pedro Emmanuel Alvarenga Americano , Fonseca Claudio Fico , Bacelo Adriana Costa
Published: January 2024

Background

Nutritional risk situations related to decreased food intake in the hospital environment hinder nutritional care and increase malnutrition in hospitalized patients and are often associated with increased morbidity and mortality. The objective of this study is to develop and test the reliability and data similarity of a mobile application as a virtual instrument to assess the acceptability and quality of hospital diets for inpatients.

Methods

This intra- and interobserver development and reliability study investigated an in-hospital food intake monitoring application based on a validated instrument for patients with infectious diseases who were treated at the Evandro Chagas National Institute of Infectious Diseases (INI/FIOCRUZ). The instrument was sequentially administered to patients 48 h after admission to INI hospital units using the printed instrument (paper) and the digital application (ARIETI) simultaneously. The tested reliability factor was the consistency of the method in the digital platform, checking whether the application provided equivalent data to the paper instrument, and finally, a statistical analysis plan was performed in the R platform version 4.2.0. This project was authorized by the FIOCRUZ/INI Research Ethics Committee.

Results

The ARIETI was developed and tested for reliability in 70 participants, showing a similar ability to calculate caloric intake in Kcal, protein intake (g), the proportion of caloric intake and protein intake relative to the prescribed goal. These instrument comparison analyses showed statistical significance (p < 0.001). The application was superior to the paper-based instrument, accelerating the time to perform the nutritional risk diagnosis based on food intake by approximately 250 s (average time).

Conclusions

The ARIETI application has demonstrated equivalent reliability compared to the original instrument. Moreover, it optimized the time between the diagnosis of nutritional risk related to dietary intake and the nutritionist’s decision making, showing an improved ability to maintain information quality compared to the paper-based instrument.
EN1 promotes lung metastasis of salivary adenoid cystic carcinoma by regulating the PI3K-AKT pathway and epithelial-mesenchymal transition
Authors: Cui Yajuan , Zhang Ye , Liu Yuping , Zhou Zheng , Zhu Lijing , Zhou Chuan-Xiang
Published: January 2024

Background

Engrailed homeobox 1 (EN1) is a candidate oncogene that is epigenetically modified in salivary adenoid cystic carcinoma (SACC). We investigated the expression of EN1 in SACC tissues and cells, EN1 promoter methylation, and the role of EN1 in tumour progression in SACC.

Methods

Thirty-five SACC samples were screened for key transcription factors that affect tumour progression. In vitro and in vivo assays were performed to determine the viability, tumorigenicity, and metastatic ability of SACC cells with modulated EN1 expression. Quantitative methylation-specific polymerase chain reaction analysis was performed on SACC samples.

Results

EN1 was identified as a transcription factor that was highly overexpressed in SACC tissues, regardless of clinical stage and histology subtype, and its level of expression correlated with distant metastasis. EN1 promoted cell invasion and migration through epithelial-mesenchymal transition in vitro and enhanced SACC metastasis to the lung in vivo. RNA-seq combined with in vitro assays indicated that EN1 might play an oncogenic role in SACC through the PI3K-AKT pathway. EN1 mRNA levels were negatively correlated with promoter hypermethylation, and inhibition of DNA methylation by 5-aza-dC increased EN1 expression.

Conclusions

The transcription factor EN1 is overexpressed in SACC under methylation regulation and plays a pivotal role in SACC progression through the PI3K-AKT pathway. These results suggest that EN1 may be a diagnostic biomarker and a potential therapeutic target for SACC.
An estrogen-regulated long non-coding RNA NCALD promotes luminal breast cancer proliferation by activating GRHL2
Authors: Meng Yue , Zhou Dianrong , Luo Ying , Chen Jierong , Li Hui
Published: January 2024

Purpose

Luminal breast cancer (BC) is a prevalent subtype associated with an increased risk of late disease recurrence and mortality. Long noncoding RNAs (lncRNAs) likely play significant roles in regulating tissue-specific gene expression during tumorigenesis. However, the biological function and underlying mechanisms of specific dysregulated lncRNAs in luminal BC remain largely unknown, which has drawn our attention.

Methods

The expression pattern of lncRNA NCALD in luminal BC was predicted and validated in collected tissue samples. Following cell transfection with knockdown of lncRNA NCALD and ESR1 and overexpression of GRHL2 and ESR1, we investigated the interactions among lncRNA NCALD, ESR1, and GRHL2. Additionally, their regulatory functions in luminal BC cell biological processes were studied. Subsequently, a xenograft tumor model was prepared for validation.

Results

Our study identified a specific overexpression of the lncRNA NCALD in luminal BC, which correlated with an unfavorable prognosis. Suppression of lncRNA NCALD or ESR1 led to inhibition of GRHL2 expression, while concurrent overexpression of ESR1 and lncRNA NCALD potentially elevated GRHL2 expression. Mechanistically, ERα may drive the expression of lncRNA NCALD. Furthermore, the 1–151 nt fragment of lncRNA NCALD was found to recruit ERα and interact with its oest-Recep domain located in the promoter region of GRHL2, ultimately inducing GRHL2 transcription.

Conclusions

These findings reveal the involvement of lncRNA NCALD and its specific expression pattern in luminal BC. Targeting lncRNA NCALD could be a potential therapeutic strategy for delaying the progression of BC.
Association of saturated fatty acids with cancer risk: a systematic review and meta-analysis
Authors: Mei Jin , Qian Meiyu , Hou Yanting , Liang Maodi , Chen Yao , Wang Cuizhe , Zhang Jun
Published: January 2024

Objective

Extensive research has explored the link between saturated fatty acids (SFAs) and cardiovascular diseases, alongside other biological dysfunctions. Yet, their association with cancer risk remains a topic of debate among scholars. The present study aimed to elucidate this association through a robust meta-analysis.

Methods

PubMed, Embase, Cochrane Library, and Web of Science databases were searched systematically to identify relevant studies published until December 2023. The Newcastle-Ottawa Scale was used as the primary metric for evaluating the quality of the included studies. Further, fixed- or random-effects models were adopted to determine the ORs and the associated confidence intervals using the Stata15.1 software. The subsequent subgroup analysis revealed the source of detection and the cancer types, accompanied by sensitivity analyses and publication bias evaluations.

Results

The meta-analysis incorporated 55 studies, comprising 38 case-control studies and 17 cohort studies. It revealed a significant positive correlation between elevated levels of total SFAs and the cancer risk (OR of 1.294; 95% CI: 1.182–1.416; P-value less than 0.001). Moreover, elevated levels of C14:0, C16:0, and C18:0 were implicated in the augmentation of the risk of cancer. However, no statistically significant correlation of the risk of cancer was observed with the elevated levels of C4:0, C6:0, C8:0, C10:0, C12:0, C15:0, C17:0, C20:0, C22:0, and C24:0. Subgroup analysis showed a significant relationship between excessive dietary SFA intake, elevated blood SFA levels, and heightened cancer risk. Increased total SFA levels correlated with higher risks of breast, prostate, and colorectal cancers, but not with lung, pancreatic, ovarian, or stomach cancers.

Conclusion

High total SFA levels were correlated with an increased cancer risk, particularly affecting breast, prostate, and colorectal cancers. Higher levels of specific SFA subtypes (C14:0, C16:0, and C18:0) are also linked to an increased cancer risk. The findings of the present study would assist in providing dietary recommendations for cancer prevention, thereby contributing to the development of potential strategies for clinical trials in which diet-related interventions would be used in combination with immunotherapy to alter the levels of SFAs in patients and thereby improve the outcomes in cancer patients. Nonetheless, further high-quality studies are warranted to confirm these associations.
Double-layered N-S1 protein nanoparticle immunization elicits robust cellular immune and broad antibody responses against SARS-CoV-2
Authors: Li Ruiqi , Chang Zejie , Liu Hongliang , Wang Yanan , Li Minghui , Chen Yilan , Fan Lu , Wang Siqiao , Sun Xueke , Liu Siyuan , Cheng Anchun , Ding Peiyang , Zhang Gaiping
Published: January 2024

Background

The COVID-19 pandemic is a persistent global threat to public health. As for the emerging variants of SARS-CoV-2, it is necessary to develop vaccines that can induce broader immune responses, particularly vaccines with weak cellular immunity.

Methods

In this study, we generated a double-layered N-S1 protein nanoparticle (N-S1 PNp) that was formed by desolvating N protein into a protein nanoparticle as the core and crosslinking S1 protein onto the core surface against SARS-CoV-2.

Results

Vaccination with N-S1 PNp elicited robust humoral and vigorous cellular immune responses specific to SARS-CoV-2 in mice. Compared to soluble protein groups, the N-S1 PNp induced a higher level of humoral response, as evidenced by the ability of S1-specific antibodies to block hACE2 receptor binding and neutralize pseudovirus. Critically, N-S1 PNp induced Th1-biased, long-lasting, and cross-neutralizing antibodies, which neutralized the variants of SARS-CoV-2 with minimal loss of activity. N-S1 PNp induced strong responses of CD4+ and CD8+ T cells, mDCs, Tfh cells, and GCs B cells in spleens.

Conclusions

These results demonstrate that N-S1 PNp vaccination is a practical approach for promoting protection, which has the potential to counteract the waning immune responses against SARS-CoV-2 variants and confer broad efficacy against future new variants. This study provides a new idea for the design of next-generation SARS-CoV-2 vaccines based on the B and T cells response coordination.

Graphical Abstract
Association between preoperative sarcopenia and prognosis of pancreatic cancer after curative-intent surgery: a updated systematic review and meta-analysis
Authors: Liu Chenming , An Liang , Zhang Siyuan , Deng Shiqing , Wang Neng , Tang Haijun
Published: January 2024

Background

Sarcopenia is associated with poor outcomes in many malignancies. However, the relationship between sarcopenia and the prognosis of pancreatic cancer has not been well understood. The aim of this meta-analysis was to identify the prognostic value of preoperative sarcopenia in patients with pancreatic cancer after curative-intent surgery.

Methods

Database from PubMed, Embase, and Web of Science were searched from its inception to July 2023. The primary outcomes were overall survival (OS), progression-free survival (PFS), and the incidence of major complications. The hazard ratio (HR), odds ratio (OR), and 95% confidence intervals (CIs) were used to assess the relationship between preoperative sarcopenia and the prognosis of patients with pancreatic cancer. All statistical analyses were conducted by Review Manager 5.3 and STATA 17.0 software.

Results

A total of 23 retrospective studies involving 5888 patients were included in this meta-analysis. The pooled results demonstrated that sarcopenia was significantly associated with worse OS (HR = 1.53, P < 0.00001) and PFS (HR = 1.55, P < 0.00001). However, this association was not obvious in regard to the incidence of major complications (OR = 1.33, P = 0.11).

Conclusion

Preoperative sarcopenia was preliminarily proved to be associated with the terrible prognosis of pancreatic cancer after surgery. However, this relationship needs to be further validated in more prospective studies.
The scaffold protein AXIN1: gene ontology, signal network, and physiological function
Authors: Qiu Lu , Sun Yixuan , Ning Haoming , Chen Guanyu , Zhao Wenshan , Gao Yanfeng
Published: January 2024

AXIN1, has been initially identified as a prominent antagonist within the WNT/β-catenin signaling pathway, and subsequently unveiled its integral involvement across a diverse spectrum of signaling cascades. These encompass the WNT/β-catenin, Hippo, TGFβ, AMPK, mTOR, MAPK, and antioxidant signaling pathways. The versatile engagement of AXIN1 underscores its pivotal role in the modulation of developmental biological signaling, maintenance of metabolic homeostasis, and coordination of cellular stress responses. The multifaceted functionalities of AXIN1 render it as a compelling candidate for targeted intervention in the realms of degenerative pathologies, systemic metabolic disorders, cancer therapeutics, and anti-aging strategies. This review provides an intricate exploration of the mechanisms governing mammalian AXIN1 gene expression and protein turnover since its initial discovery, while also elucidating its significance in the regulation of signaling pathways, tissue development, and carcinogenesis. Furthermore, we have introduced the innovative concept of the AXIN1-Associated Phosphokinase Complex (AAPC), where the scaffold protein AXIN1 assumes a pivotal role in orchestrating site-specific phosphorylation modifications through interactions with various phosphokinases and their respective substrates.
Cross-sectional associations between 24-hour time-use composition, grey matter volume and cognitive function in healthy older adults
Authors: Mellow Maddison L , Dumuid Dorothea , Olds Timothy , Stanford Ty , Dorrian Jillian , Wade Alexandra T , Fripp Jurgen , Xia Ying , Goldsworthy Mitchell R , Karayanidis Frini , Breakspear Michael J , Smith Ashleigh E
Published: January 2024

Background

Increasing physical activity (PA) is an effective strategy to slow reductions in cortical volume and maintain cognitive function in older adulthood. However, PA does not exist in isolation, but coexists with sleep and sedentary behaviour to make up the 24-hour day. We investigated how the balance of all three behaviours (24-hour time-use composition) is associated with grey matter volume in healthy older adults, and whether grey matter volume influences the relationship between 24-hour time-use composition and cognitive function.

Methods

This cross-sectional study included 378 older adults (65.6 ± 3.0 years old, 123 male) from the ACTIVate study across two Australian sites (Adelaide and Newcastle). Time-use composition was captured using 7-day accelerometry, and T1-weighted magnetic resonance imaging was used to measure grey matter volume both globally and across regions of interest (ROI: frontal lobe, temporal lobe, hippocampi, and lateral ventricles). Pairwise correlations were used to explore univariate associations between time-use variables, grey matter volumes and cognitive outcomes. Compositional data analysis linear regression models were used to quantify associations between ROI volumes and time-use composition, and explore potential associations between the interaction between ROI volumes and time-use composition with cognitive outcomes.

Results

After adjusting for covariates (age, sex, education), there were no significant associations between time-use composition and any volumetric outcomes. There were significant interactions between time-use composition and frontal lobe volume for long-term memory (p = 0.018) and executive function (p = 0.018), and between time-use composition and total grey matter volume for executive function (p = 0.028). Spending more time in moderate-vigorous PA was associated with better long-term memory scores, but only for those with smaller frontal lobe volume (below the sample mean). Conversely, spending more time in sleep and less time in sedentary behaviour was associated with better executive function in those with smaller total grey matter volume.

Conclusions

Although 24-hour time use was not associated with total or regional grey matter independently, total grey matter and frontal lobe grey matter volume moderated the relationship between time-use composition and several cognitive outcomes. Future studies should investigate these relationships longitudinally to assess whether changes in time-use composition correspond to changes in grey matter volume and cognition.
Impact of Ebola and COVID-19 on maternal, neonatal, and child health care among populations affected by conflicts: a scoping review exploring demand and supply-side barriers and solutions
Authors: Shafiq Yasir , Rubini Elena , Fazal Zoha Zahid , Bukhari Muhammad Murtaza , Zakaria Maheen , Zeeshan Noor ul Huda , Muhammad Ameer , Ragazzoni Luca , Barone-Adesi Francesco , Valente Martina
Published: January 2024

Introduction

Armed conflicts have a severe impact on the health of women and children. Global health emergencies such as pandemics and disease outbreaks further exacerbate the challenges faced by vulnerable populations in accessing maternal, neonatal, and child healthcare (MNCH). There is a lack of evidence that summarizes the challenges faced by conflict-affected pregnant women, mothers, and children in accessing MNCH services during global health emergencies, mainly the Ebola and COVID-19 pandemics. This scoping review aimed to analyze studies evaluating and addressing barriers to accessing comprehensive MNCH services during Ebola and COVID-19 emergencies in populations affected by conflict.

Methods

The search was conducted on PubMed, Scopus, and Web of Science databases using terms related to Ebola and COVID-19, conflicts, and MNCH. Original studies published between 1990 and 2022 were retrieved. Articles addressing the challenges in accessing MNCH-related services during pandemics in conflict-affected settings were included. Thematic analysis was performed to categorize the findings and identify barriers and solutions.

Results

Twenty-nine studies met the inclusion criteria. Challenges were identified in various MNCH domains, including antenatal care, intrapartum care, postnatal care, vaccination, family planning, and the management of childhood illnesses. Ebola-related supply-side challenges mainly concerned accessibility issues, health workforce constraints, and the adoption of stringent protocols. COVID-19 has resulted in barriers related to access to care, challenges pertaining to the health workforce, and new service adoption. On the demand-side, Ebola- and COVID-19-related risks and apprehensions were the leading barriers in accessing MNCH care. Community constraints on utilizing services during Ebola were caused by a lack of trust and awareness. Demand-side challenges of COVID-19 included fear of disease, language barriers, and communication difficulties. Strategies such as partnerships, strengthening of health systems, service innovation, and community-based initiatives have been employed to overcome these barriers.

Conclusion

Global health emergencies amplify the barriers to accessing MNCH services faced by conflict-affected populations. Cultural, linguistic, and supply-side factors are key challenges affecting various MNCH domains. Community-sensitive initiatives enhancing primary health care (PHC), mobile clinics, or outreach programs, and the integration of MNCH into PHC delivery should be implemented. Efforts should prioritize the well-being and empowerment of vulnerable populations. Addressing these barriers is crucial for achieving universal health coverage and the Sustainable Development Goals.
Revealing third-order interactions through the integration of machine learning and entropy methods in genomic studies
Authors: Yaldız Burcu , Erdoğan Onur , Rafatov Sevda , Iyigün Cem , Aydın Son Yeşim
Published: January 2024

Background

Non-linear relationships at the genotype level are essential in understanding the genetic interactions of complex disease traits. Genome-wide association Studies (GWAS) have revealed statistical association of the SNPs in many complex diseases. As GWAS results could not thoroughly reveal the genetic background of these disorders, Genome-Wide Interaction Studies have started to gain importance. In recent years, various statistical approaches, such as entropy-based methods, have been suggested for revealing these non-additive interactions between variants. This study presents a novel prioritization workflow integrating two-step Random Forest (RF) modeling and entropy analysis after PLINK filtering. PLINK-RF-RF workflow is followed by an entropy-based 3-way interaction information (3WII) method to capture the hidden patterns resulting from non-linear relationships between genotypes in Late-Onset Alzheimer Disease to discover early and differential diagnosis markers.

Results

Three models from different datasets are developed by integrating PLINK-RF-RF analysis and entropy-based three-way interaction information (3WII) calculation method, which enables the detection of the third-order interactions, which are not primarily considered in epistatic interaction studies. A reduced SNP set is selected for all three datasets by 3WII analysis by PLINK filtering and prioritization of SNP with RF-RF modeling, promising as a model minimization approach. Among SNPs revealed by 3WII, 4 SNPs out of 19 from GenADA, 1 SNP out of 27 from ADNI, and 4 SNPs out of 106 from NCRAD are mapped to genes directly associated with Alzheimer Disease. Additionally, several SNPs are associated with other neurological disorders. Also, the genes the variants mapped to in all datasets are significantly enriched in calcium ion binding, extracellular matrix, external encapsulating structure, and RUNX1 regulates estrogen receptor-mediated transcription pathways. Therefore, these functional pathways are proposed for further examination for a possible LOAD association. Besides, all 3WII variants are proposed as candidate biomarkers for the genotyping-based LOAD diagnosis.

Conclusion

The entropy approach performed in this study reveals the complex genetic interactions that significantly contribute to LOAD risk. We benefited from the entropy-based 3WII as a model minimization step and determined the significant 3-way interactions between the prioritized SNPs by PLINK-RF-RF. This framework is a promising approach for disease association studies, which can also be modified by integrating other machine learning and entropy-based interaction methods.
Stability indicating eco-friendly quantitation of terbutaline and its pro-drug bambuterol using quantitative proton nuclear magnetic spectroscopy
Authors: El-Sayed Asmaa , Sabry Mohamed A. , Elmansi Heba , Eid Manal , Shalan Shereen
Published: January 2024

Quantitative 1H-NMR became an increasingly important issue in pharmaceutical analytical chemistry. This study used NMR spectroscopy to assay the bronchodilator drug terbutaline sulfate and its pro-drug bambuterol hydrochloride in pure form and pharmaceutical preparations. The technique proceeded using deuterium oxide (D2O) as an 1H-NMR solvent and phloroglucinol anhydrous as an internal standard (IS). Comparatively, to the phloroglucinol signal at 5.9 ppm, the resulting quantitative signals of the studied drugs were corrected. The terbutaline singlet signal at 6.3 ppm was chosen for quantification, while the bambuterol quantitative singlet signal was at 2.9 ppm. The two drugs were rectilinear over the concentration range of 1.0–16.0 mg/mL. LOD values were 0.19 and 0.21 mg/mL while LOQ values were 0.58 and 0.64 mg/mL for terbutaline and bambuterol respectively. The developed method has been validated according to the International Conference of Harmonization (ICH) regarding linearity, accuracy, precision, specificity, and robustness. A greenness profile assessment was applied, and the method proved to be green. The method enables the assay of the two drugs in pure drug and pharmaceutical preparations. The method also enables the assay of the two drugs in the presence of each other; thus, it is considered a stability-indicating method where terbutaline is an acid degradation product of bambuterol.
CRAFT: a web-integrated cavity prediction tool based on flow transfer algorithm
Authors: Gahlawat Anuj , Singh Anjali , Sandhu Hardeep , Garg Prabha
Published: January 2024

Numerous computational methods, including evolutionary-based, energy-based, and geometrical-based methods, are utilized to identify cavities inside proteins. Cavity information aids protein function annotation, drug design, poly-pharmacology, and allosteric site investigation. This article introduces “flow transfer algorithm” for rapid and effective identification of diverse protein cavities through multidimensional cavity scan. Initially, it identifies delimiter and susceptible tetrahedra to establish boundary regions and provide seed tetrahedra. Seed tetrahedron faces are precisely scanned using the maximum circle radius to transfer seed flow to neighboring tetrahedra. Seed flow continues until terminated by boundaries or forbidden faces, where a face is forbidden if the estimated maximum circle radius is less or equal to the user-defined maximum circle radius. After a seed scanning, tetrahedra involved in the flow are clustered to locate the cavity. The CRAFT web interface integrates this algorithm for protein cavity identification with enhanced user control. It supports proteins with cofactors, hydrogens, and ligands and provides comprehensive features such as 3D visualization, cavity physicochemical properties, percentage contribution graphs, and highlighted residues for each cavity. CRAFT can be accessed through its web interface at http://pitools.niper.ac.in/CRAFT, complemented by the command version available at https://github.com/PGlab-NIPER/CRAFT/.

Scientific contribution

Flow transfer algorithm is a novel geometric approach for accurate and reliable prediction of diverse protein cavities. This algorithm employs a distinct concept involving maximum circle radius within the 3D Delaunay triangulation to address diverse van der Waals radii while existing methods overlook atom specific van der Waals radii or rely on complex weighted geometric techniques.
Unraveling data from an idea management system of 11 radical innovation portfolios: key lessons and avenues for artificial intelligence integration
Authors: Jakobsen Henning Sejer , Brix Jacob , Jakobsen Rune Sejer
Published: January 2024

In strategic and radical innovation, the degree of uncertainty and the amount of complexity is much higher compared to ‘business as usual’. Therefore, idea management systems are often used to support such innovation processes. An interesting question is what we can learn from studying data in such idea management systems and what potential implications we can derive from the innovation management literature. In this study, we were allowed to access and analyze data from the same idea management system used in 11 radical innovation projects from the years 2012–2018. Our analysis unravels 8 findings that in different ways nuance or challenge current research on innovation management. Finally, we discuss how the integration of artificial intelligence (AI) in idea management systems can support innovation team members in increasing the innovation potential of the ideas that are elaborated.
Association between regional critical care capacity and the incidence of invasive mechanical ventilation for coronavirus disease 2019: a population-based cohort study
Authors: Ohbe Hiroyuki , Hashimoto Satoru , Ogura Takayuki , Nishikimi Mitsuaki , Kudo Daisuke , Shime Nobuaki , Kushimoto Shigeki
Published: January 2024

Background

Coronavirus disease 2019 (COVID-19) has exposed critical care supply shortages worldwide. This study aimed to investigate the association between regional critical care capacity and the incidence of invasive mechanical ventilation following novel COVID-19 during the pandemic in Japan, a country with a limited intensive care unit (ICU) bed capacity of a median of 5.1 ICU beds per 100,000 individuals.

Methods

This population-based cohort study used data from the CRoss Icu Searchable Information System database and publicly available databases provided by the Japanese government and Japanese Society of Intensive Care Medicine. We identified patients recently diagnosed with COVID-19, those who received invasive mechanical ventilation, and those who received extracorporeal membrane oxygenation (ECMO) between February 2020 and March 2023. We analyzed the association between regional critical care capacity (ICU beds, high-dependency care unit (HDU) beds, resource-rich ICU beds, and intensivists) and the incidence of invasive mechanical ventilation, ECMO, and risk-adjusted mortality across 47 Japanese prefectures.

Results

Among the approximately 127 million individuals residing in Japan, 33,189,809 were recently diagnosed with COVID-19, with 12,203 and 1,426 COVID-19 patients on invasive mechanical ventilation and ECMO, respectively, during the study period. Prefecture-level linear regression analysis revealed that the addition of ICU beds, resource-rich ICU beds, and intensivists per 100,000 individuals increased the incidence of IMV by 5.37 (95% confidence interval, 1.99–8.76), 7.27 (1.61–12.9), and 13.12 (3.48–22.76), respectively. However, the number of HDU beds per 100,000 individuals was not statistically significantly associated with the incidence of invasive mechanical ventilation. None of the four indicators of regional critical care capacity was statistically significantly associated with the incidence of ECMO and risk-adjusted mortality.

Conclusions

The results of prefecture-level analyses demonstrate that increased numbers of ICU beds, resource-rich ICU beds, and intensivists are associated with the incidence of invasive mechanical ventilation among patients recently diagnosed with COVID-19 during the pandemic. These findings have important implications for healthcare policymakers, aiding in efficiently allocating critical care resources during crises, particularly in regions with limited ICU bed capacities.

Registry and the registration no. of the study/trial The approval date of the registry was August 20, 2020, and the registration no. of the study was lUMIN000041450.
Application of a weighted ensemble forecasting method based on online learning in subseasonal forecast in the South China
Authors: Xin Fei , Shen Yichen , Lu Chuhan
Published: January 2024

Under the proposal of “seamless forecasting”, it has become a key problem for meteorologists to improve the skills of subseasonal forecasts. Since the launch of the subseasonal-to-seasonal (S2S) plan by WMO, the precision of model predictions has been further developed. However, when we are focusing on the practical applications of models in the South China (SC) in recent years, we found that large disagreements appear between forecast members. Some of the members predicted well in this area, while others are not satisfactory. To improve the accuracy of subseasonal forecast in the SC, new methods making full use of different forecast models must be proposed. In this passage, we introduced a weighted ensemble forecasting method based on online learning (OL) to overcome this difficulty. As the state-of-the-art forecast models in the world, three models from China Meteorological Administration, European Centre for Medium-Range Weather Forecasts and National Centers for Environmental Prediction provided by the S2S prediction dataset are used as ensemble members, and an ensemble weight is trained through the aforementioned OL model for the predictions of temperature and precipitation in subseasonal timescale in the SC. The results show that the forecast results produced under the OL method are better than the original model predictions. Compared with the three model ensemble results, the weighted ensemble model has a good ability in depicting the temperature and precipitation in the SC. Furthermore, we also compared this strategy against the climatology predictions and found out that the weighted ensemble model is superior in 10–30 days. Thus, the weighted ensemble method trained thorough OL may shed light on improving the skill of subseasonal forecasts.
Publicly available data sources in sport-related concussion research: a caution for missing data
Authors: Bretzin Abigail C. , D’Alonzo Bernadette A. , van der Mei Elsa R. , Gravel Jason , Wiebe Douglas J.
Published: January 2024

Background

Researchers often use publicly available data sources to describe injuries occurring in professional athletes, developing and testing hypotheses regarding athletic-related injury. It is reasonable to question whether publicly available data sources accurately indicate athletic-related injuries resulting from professional sport participation. We compared sport-related concussion (SRC) clinical incidence using data from publicly available sources to a recent publication reporting SRC using electronic health records (EHR) from the National Football League (NFL). We hypothesize publicly available data sources will underrepresent SRC in the NFL. We obtained SRCs reported from two publicly available data sources (NFL.com, pro-football-reference.com) and data reported from the NFL’s published EHR. We computed SRC per 100 unique player signings from 2015–2019 and compared the clinical incidence from publicly available data sources to EHR rates using clinical incidence ratios (CIR) and 95% confidence intervals (CI).

Findings

From 2015–2019, SRC counts from published EHR record data ranged from 135–192 during the regular season, whereas SRC counts ranged from 102–194 and 69–202 depending on the publicly available data source. In NFL.com the SRC clinical incidence was significantly and progressively lower in 2017 (CIR: 0.73, 95% CI: 0.58–0.91), 2018 (CIR: 0.66, 95% CI: 0.50–0.87), and 2019 (CIR: 0.48, 95% CI: 0.35–0.64) relative to the gold-standard EHR. In the pro-football-reference.com data, the documented SRCs in publicly available data sources for other years were ~ 20–30% lower than the gold-standard EHR numbers (CIRs 0.70–0.81).

Conclusions

Publicly available data for SRCs per 100 unique player signings did not match published data from the NFL’s EHR and in several years were significantly lower. Researchers should use caution before using publicly available data sources for injury research.
Morpho-molecular characterization of two Syrian soil-sourced isolates of Beauveria (Bals.) Vuill.
Authors: Rajab Lobna , Ahmad Mohammad , Gazal Ibtisam
Published: January 2024

Background

The genus Beauveria (Bals.) Vuill. includes many species, some of which are limited to specific regions while others are distributed worldwide. The diversity of Beauveria species is poorly investigated in Syria and most studies lack proper diagnosis of species. Entomopathogenic isolates of this genus were obtained using the Galleria Bait Method. This study aimed to identify these isolates based on morphological characterizations combined with molecular data, using nuclear ribosomal internal transcribed spacer (ITS) and elongation factor 1-alpha (EF1-α) sequences. The diversity of this genus in Syria has also been evaluated using a phylogenetic analysis of available ITS sequences of Syrian isolates in the GenBank.

Results

Two entomopathogenic isolates, B195 and B243, were detected in the soil of agro-ecosystems in the Syrian coastal region. Morphological and molecular information revealed that these two isolates belong to Beauveria bassiana (Bals.) Vuill. (Hypocreales: Cordycipitaceae) with 514 bp and 284 bp for the sequences of each isolate for ITS and EF1-α, respectively. Pathogenicity test showed 100% mortality of Galleria mellonella L. larvae 2–3 days post-fungal exposure for both isolates. The phylogenetic tree showed that all Syrian sequences of Beauveria clustered within the species B. bassiana, with a considerable intraspecific diversity, except for two isolates previously identified as B. bassiana, which are closely related to Beuveria pseudobassiana S.A. Rehner and Humber.

Conclusions

This study presents a morpho-molecular characterization of two Syrian soil-sourced B. bassiana isolates highly pathogenic to G. mellonella larvae and clarifies their phylogenetic placement. Depending on our findings, further exploration studies of the genus Beauveria in Syria are still needed to better our understanding of the diversity and distribution of this entomopathogen in Syria.