bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk factors associated with Crimean-Congo hemorrhagic fever virus circulation among human, livestock and ticks in Mauritania through a one health retrospective study
Authors: El Ghassem Abdellahi , Apolloni Andrea , Vial Laurence , Bouvier Romain , Bernard Celia , Khayar Mariem Seyidna , Cheikh Ahmed Mariem , Fausther-Bovendo Hugues , Beyit Abdallahi Diambar , Yahya Barry , Ould El Mamy Mohamed Bezeid , Elbara Ahmed , Bollahi Mohamed Abdellahi , Cêtre-Sossah Catherine , Ould Mohamed Salem Boukhary Ali
Published: November 2023

Background

Crimean Congo hemorrhagic fever (CCHF) is endemic in Southern Mauritania where recurrent outbreaks have been constantly observed since the 1980’s. The present study is the first to assess CCHFV antibodies and RNA in humans.

Methods

A retrospective study was conducted using 263 humans and 1380 domestic animals serum samples, and 282 tick specimens of Hyalomma genus collected from 54 settings in 12 provinces across Mauritania. Antibodies targeting CCHF viral nucleoprotein were detected in animal and human sera using double-antigen ELISA. CCHFV specific RNA was detected in human and animal sera as well as tick supernatants using a CCHFV real time RT-PCR kit. Individual characteristics of sampled hosts were collected at the same time and data were geo-referenced. Satellite data of several environmental and climatic factors, were downloaded from publicly available datasets, and combined with data on livestock mobility, animal and human density, road accessibility and individual characteristics to identify possible risk factors for CCHFV spatial distribution. To this end, multivariate logistic models were developed for each host category (human, small and large ruminants).

Results

The overall CCHFV antibody prevalence was 11.8% [95% CI: 8.4–16.3] in humans (17.9% in 2020 and 5.4% in 2021; p = 0.0017) and 33.1% (95% CI: 30.1–36.3) in livestock. CCHFV-specific antibodies were detected in 91 (18.1%) out of 502 sheep, 43 (9.0%) out of 477 goats, 144 (90.5%) out of 161 dromedaries and 179 (74.6%) out of 240 cattle. CCHFV RNA was detected in only 2 (0.7%) sera out of 263 animals herders samples from Hodh El Gharbi province and in 32 (11.3%) out of 282 Hyalomma ticks. In humans as well as in animals, seropositivity was not associated with sex or age groups. The multivariate analysis determined the role of different environmental, climatic and anthropic factors in the spatial distribution of the disease with animal mobility and age being identified as risk factors.

Conclusion

Results of the present study demonstrate the potential risk of CCHF for human population in Mauritania primarily those living in rural areas in close vicinity with animals. Future studies should prioritize an integrative human and veterinary approach for better understanding and managing Crimean-Congo hemorrhagic fever.
Novel approach of prophylactic radiation to reduce toxicities comparing 2-step40 with 56-Gy simultaneous integrated boost intensity-modulated radiation therapy for locally advanced squamous cell carcinoma of the head and neck, an intergroup phase III trial (JCOG1912, NEW BRIDGE)
Authors: Yokota Tomoya , Zenda Sadamoto , Kodaira Takeshi , Kiyota Naomi , Fujimoto Yasushi , Wasano Koichiro , Takahashi Ryo , Mizowaki Takashi , Homma Akihiro , Sasaki Keita , Machida Ryunosuke , Sekino Yuta , Fukuda Haruhiko ,   Japan Clinical Oncology Group Radiation Therapy Study Group,   Japan Clinical Oncology Group Head and Neck Cancer Study Group
Published: November 2023

Background

Chemoradiotherapy (CRT) with concurrent cisplatin is the standard of care as a nonsurgical definitive treatment for patients with locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). However, CRT is associated with increased severe late adverse events, including swallowing dysfunction, xerostomia, ototoxicity, and hypothyroidism. Few strategies aimed at less invasive CRT without compromising treatment outcomes have been successful. The purpose of this study is to confirm the non-inferiority of reduced dose prophylactic radiation with 40 Gy compared to standard dose prophylactic radiation with 56 Gy in terms of the time to treatment failure (TTF) among patients with clinical stage III-IVB LA-SCCHN.

Methods

This study is a multicenter, two-arm, open-label, randomized phase III trial. Patients with LA-SCCHN excluding p16 positive oropharynx cancer are randomized to the standard arm or experimental arm. A total dose of 70 Gy for tumors with concurrent cisplatin at 100 mg/m2 are administered in both arms. For prophylactic field, patients in the standard arm receive a total dose of 56 Gy in 35 fractions for 7 weeks using simultaneous integrated boost (SIB56) and those in the experimental arm receive 40 Gy in 20 fractions using two-step methods for 4 weeks (2-step40). A total of 400 patients will be enrolled from 52 Japanese institutions within 5 years. The primary endpoint is TTF, and the secondary endpoints are overall survival, complete response rate, progression-free survival, locoregional relapse-free survival, acute and late adverse events, quality of life score, and swallowing function score.

Discussion

If the experimental arm is non-inferior to the standard arm in terms of TTF and superior on the safety endpoints, the 2-step40 procedure is the more useful treatment than SIB56 for definitive CRT.

Trial registration

This trial has been registered in the Japan Registry of Clinical Trials as jRCTs031210100 (https://jrct.niph.go.jp/latest-detail/jRCTs031210100). Date of Registration: May 2021.
A pan-cancer analysis revealing the role of LFNG, MFNG and RFNG in tumor prognosis and microenvironment
Authors: Gong Xun , Zheng Chenglong , Jia Haiying , Liu Yangruiyu , Yang Rui , Chen Zizhou , Pan Yihang , Li Xiaowu , Liu Yuchen
Published: November 2023

Background

Fringe is a glycosyltransferase involved in tumor occurrence and metastasis. However, a comprehensive analysis of the Fringe family members lunatic fringe (LFNG), manic fringe (MFNG), radical fringe (RFNG) in human cancers is lacking.

Methods

In this study, we performed a pan-cancer analysis of Fringe family members in 33 cancer types with transcriptomic, genomic, methylation data from The Cancer Genome Atlas (TCGA) project. The correlation between Fringe family member expression and patient overall survival, copy number variation, methylation, Gene Ontology enrichment, and tumor-infiltrating lymphocytes (TILs) was investigated by using multiple databases, such as cBioPortal, Human Protein Atlas, GeneCards, STRING, MSigDB, TISIDB, and TIMER2. In vitro experiments and immunohistochemical assays were performed to validate our findings.

Results

High expression levels of LFNG, MFNG, RFNG were closely associated with poor overall survival in multiple cancers, particularly in pancreatic adenocarcinoma (PAAD), uveal melanoma (UVM), and brain lower-grade glioma (LGG). Copy number variation analysis revealed that diploid and gain mutations of LFNG was significantly increased in PAAD and stomach adenocarcinoma (STAD), and significantly associated with the methylation levels in promoter regions. Significant differential genes between high and low expression groups of these Fringe family members were found to be consistently enriched in immune response and T cell activation pathway, extracellular matrix adhesion pathway, RNA splicing and ion transport pathways. Correlation between the abundance of tumor-infiltrating lymphocytes (TILs) and LFNG, MFNG, and RFNG expression showed that high LFNG expression was associated with lower TIL levels, particularly in PAAD. In vitro experiment by using pancreatic cancer PANC1 cells showed that LFNG overexpression promoted cell proliferation and invasion. Immunohistochemical assay in 90 PAAD patients verified the expression level of LFNG and its relationship with the prognosis.

Conclusions

Our study provides a relatively comprehensive understanding of the expression, mutation, copy number, promoter methylation level changes along with prognosis values of LFNG, MFNG, and RFNG in different tumors. High LFNG expression may serve as a poor prognosis molecular marker for PAAD.
Suicide attempt among Malaysian school-going adolescents: relationship with bullying
Authors: Liew Siaw Hun , Razak Mohamad Aznuddin Abd , Kassim Mohd Shaiful Azlan , Ahmad Noor Ani , Tan LeeAnn
Published: November 2023

Background

According to World Health Organization (WHO), the fourth leading cause of death among adolescents aged 15 -19 years is suicide. The National Health and Morbidity Survey (NHMS) 2017 reported that suicidal attempts among school adolescents increased from 6.8%—6.9% as compared to NHMS 2012. Suicide attempts can cause significant negative impacts on health, social and economic status. Bullying is one of the factors for adolescent suicide attempts, and its relationship to suicidality in adolescents has been shown in numerous research.

Objectives

This study examined the relationship between suicide attempts and bullying among school adolescents in Malaysia.

Methods

Data from the Malaysia NHMS 2017, a nationwide study that adopted a two-stage cluster sampling design, were analysed. The survey used a self-administered questionnaire in bilingual language adapted from GSHS developed by WHO. Participants were secondary school students aged 13 -17 in all states. Descriptive and multiple logistic regression analyses were performed using IBM SPSS version 28.

Results

A total of 27,497 school adolescents participated in the study. Results showed that 6.9% of school adolescents had attempted suicide. There was 16.2% of adolescents being bullied. Multiple logistic regression revealed that students who were bullied were more likely to have suicide attempts (aOR 4.827, 95% CI: 4.143, 5.624) P < 0.001.

Discussion/conclusion

This study revealed that bullying is associated with suicide attempts among school adolescents in Malaysia. The respective authority should consider and plan effective measures to curb bullying among school adolescents.
The development and evaluation of the worker-occupation fit inventory
Authors: Lv Keyao , Sun Ruican , Chen Xiaofang , Lan Yajia
Published: November 2023

Background

Person-environment fit (PEF) theory, one of the foundational theories of occupational stress, has primarily found applications in organizational behavior and human resource management. Given the alignment between the definition of occupational stress and the essence of PEF, we introduced the concept of worker-occupation fit (WOF). To validate our theoretical model, the development of an instrument to measure WOF becomes imperative.

Methods

The Worker-Occupation Fit Inventory (WOFI) comprises three dimensions: personal trait fit (PTF), need-supply fit (NSF) and demand-ability fit (DAF). Job-related mental disorders (JRMDs) were assessed using the DASS-21. During the pre-investigation, items of the WOFI underwent screening through classic test theory (CTT) analysis. In the formal investigation, item response theory (IRT) analysis was employed to evaluate the selected items. The relationship between WOF and JRMD was verified by Pearson’s correlation analysis and multiple logistic regression analysis.

Results

The initial version consisted of 26 items. Three common factors were extracted by exploratory factor analysis (EFA): 6 items were included in the PTF, 6 items were included in the NSF, 4 items were included in the DAF, and 10 items were deleted because of unacceptable factor loadings. The confirmatory factor analysis (CFA) verified the structure of the WOFI with χ2/df = 1.822, CFI = 0.947, and SRMSR = 0.056. The Cronbach's alpha coefficients of the PTF, NSF, and DAF were 0.91, 0.92, and 0.80, respectively. In IRT analysis, the discrimination values of all items ranged from 1.25 to 2.53, and the difficulty values of all items ranged from -6.28 to 1.30 (with no difficulty of reversal). The WOF was negatively related to job-related stress (r = -0.34, p<0.001), anxiety (r = -0.37, p<0.001), and depression (r = -0.41, p<0.001). The multiple logistic regression analysis suggested that a high level of WOF was a protective factor against job-related mental disorders, with ORs all less than 1 (p<0.001), and a low level of WOF was a risk factor for job-related mental disorders, with ORs all more than 1.0 (p<0.001).

Conclusions

The results of CTT and IRT analysis indicated that the WOFI exhibits reliability and validation. The WOF effectively predicted job-related mental disorders. Subsequent studies will delve into the influence of WOFI on diverse professions and various health outcomes.
A comparative analysis of road and vehicle qualities as factors of road traffic carnage in Nigeria
Authors: Eneh Onyenekenwa Cyprian , Okosun Andy , Egbenta Idu R , Obi Nicholas I , Oloto Martin C , Ubani Obinna , Eneh Chinemelum A , Eneonwo Cosmas I
Published: November 2023

Background and objective

Carnage on roads is a growing concern in Nigeria. Over 27 persons, equivalent to more than 4 families, die daily from road traffic crashes. Two direct factors of a road crash are road quality and vehicle quality. To interrogate and compare both factors to road traffic accidents, the longitudinal study regressed secondary data on death tolls against road quality and vehicle quality.

Materials and methods

Data on the estimated number of vehicles imported into Nigeria (1992–2021) served as the indicator of vehicle quality on Nigerian roads. The longitudinal study regressed secondary data on death tolls (2013–2019) against road quality (2006–2019) and vehicle quality (1992–2021).

Results

Results showed that road quality is degenerating as well as vehicle quality in Nigeria, resulting in increase in the number of road traffic crashes and the attendant death tolls. For every 1% decrease in road quality, death tolls from road traffic crashes in Nigeria increased by 0.00642% at 5% significance, and for every decrease in vehicle quality, death tolls from road traffic crashes in Nigeria increased by 0.327% at 5% significance.

Conclusion

The study recommended increased advocacy on the sanctity of life and the need for all tiers of government to prioritize policy and implementation of improving the road quality and vehicle quality to reduce road traffic crashes and save lives on Nigerian roads.
Atypical presentations of primary acquired hypothyroidism – a case series
Authors: Pravin R. R. , Kan Sheau Yun , Soh Ser Yee , Chan Daniel , Farhad Vasanwala Rashida
Published: November 2023

Primary acquired hypothyroidism in children manifests with a myriad of clinical presentations. Clinical features can be insidious in nature, often under the guise of non-specific presentations to other subspecialties prior to referral to the endocrinologist. Growth failure is a hallmark feature in these children alongside their presenting clinical symptomology which needs to be identified through detailed history, physical examination and analysis of the growth charts. In this case series, we discuss 5 atypical presentations of acquired primary hypothyroidism with multisystemic involvement, including musculoskeletal, hepatobiliary, gynaecological and haematological manifestations. This is of importance as untreated hypothyroidism leads to fatigue, decreased physical activity, suboptimal height gain, disordered puberty and poor neurocognitive development in children with long term detrimental outcomes.
Socio-demographic predictors of obesity among women in Mukono Central Division in Central Uganda: a cross-sectional study
Authors: Athieno Justine , Seera Georgina , Mayanja Namayengo Faith Muyonga , Galabuzi Joweria Nambooze , Namasaba Mariam
Published: November 2023

Background

There is a steadily increasing trend in obesity globally and in Sub-Saharan Africa that disproportionately affects women in most places. This is not different in Uganda, where the Uganda Demographic and Health Survey indicated an increase in obesity among women of reproductive age as measured by the body mass index (BMI). However, studies on the predictors of obesity in women are still limited. Particularly, studies using specific indicators of body fat are scant. This study explored the socio-demographic predictors of obesity as indicated by total body fat percentage among women in the age range of 18 to 69 years old living in Mukono Central Division in Central Uganda.

Methods

A cross sectional study design using quantitative methods was employed. A total of 384 women between 18 and 69 years old from Mukono Central Division in Central Uganda were randomly recruited. A structured questionnaire was used to collect socio-demographic data including age, level of education, marital status, childbearing status, household expenditure, household size and employment status. Total body fat percentage, the indicator for obesity was measured using the body composition meter from TANITA. The data was analyzed using multinomial logistic regression analysis using SPSS version 20.

Results

155 women, nearly two fifths (40.4% CI 95% 38.4–42.4) were classified as obese. Age, marital status, childbearing status, and employment status were the factors that were associated with obesity among these women. Employment status was the only variable that remained significantly associated with obesity among the women after adjusting for other factors. Unemployed women were nearly two times more likely to be obese than the employed women (AOR 1.9; 95% CI 1.1–3.1). The prevalence of obesity among the unemployed and employed women was 48.2% and 34.4% respectively.

Conclusions

Obesity in women was predicted by employment status. An in-depth study on factors that predispose unemployed women to obesity, will be instrumental in guiding interventions to curb the emerging obesity epidemic in Uganda. In the same vein, strategies to reduce levels of unemployment among women living in urban Uganda are essential for protecting public health from the dimension of reducing obesity levels.
A deep learning-based automated algorithm for labeling coronary arteries in computed tomography angiography images
Authors: Ren Pengling , He Yi , Guo Ning , Luo Nan , Li Fang , Wang Zhenchang , Yang Zhenghan
Published: November 2023

Objective

Using two three-dimensional U-Net architectures for myocardium structure extraction and a distance transformation algorithm specifically for the left circumflex artery, we have designed a fully automated algorithm for coronary artery labeling in coronary computed tomography angiography (CCTA) images.

Methods

In this retrospective analysis, a cohort of 157 patients who had undergone coronary computed tomography angiography (CCTA) was included. An automated coronary artery labeling algorithm was developed using a distance transformation approach to delineate the anatomical segments along the centerlines extracted from the CCTA images. A total of 16 segments were successfully identified and labeled. The algorithm’s outcomes were recorded and reviewed by three experts, and the performance of segment detection and labeling was assessed. Additionally, the level of agreement in manually labeled segments between two experts was quantified.

Results

When comparing the labels generated by the experts with those produced by the algorithm, it was necessary to modify or eliminate 117 labels (5.4%) out of 2180 segments assigned by the algorithm. The overall accuracy for label presence was 96.2%, with an average overlap of 94.0% between the expert reference and algorithm-generated labels. Furthermore, the average agreement rate between the two experts stood at 95.0%.

Conclusions

Based on the labels of the clinical experts, the proposed deep learning algorithm exhibits high accuracy for automatic labeling. Therefore, our proposed method exhibits promising results for the automatic labeling of the coronary arteries and will alleviate the burden on radiologists in the near future.
“I use salt. However, I also use soy sauce, oyster sauce, sometimes chili sauce and….”: interviews with Australians of Chinese ancestry regarding reducing salt consumption for hypertension prevention
Authors: Chan Alex , Kinsman Leigh , Chan Sally Wai-chi
Published: November 2023

Background

High dietary salt consumption is a significant health issue in Chinese populations. This study identified the facilitators for and barriers to salt reduction for prevention of hypertension among Chinese Australians.

Methods

An inductive qualitative study with semi-structured interviews (n = 8) was conducted with convenience samples recruited from social media. Adults who a) were over 18 years old, b) were of Chinese ancestry and c) had lived in Australia for at least 6 months were eligible for participation. Interview transcripts were transcribed and analysed using content analysis.

Results

Four facilitators for and eight barriers to reducing salt consumption were synthesised from the narrative materials. The facilitators were: 1) individual perceptions of health benefits, 2) salt alternatives, 3) digital information and 4) increased awareness of negative health impacts from a high-salt diet. The barriers identified were: 1) negative physical changes not apparent, 2) inadequate salt-related health education, 3) hidden salt in food products, 4) inadequate food literacy, 5) pricing, 6) busy lifestyle, 7) low perceived susceptibility and 8) individual food taste preference and cooking habits. Peer and family influence had positive and negative effects on participants’ likelihood of reducing salt consumption.

Conclusions

The facilitators for and barriers to maintaining a low-salt diet in Chinese Australians were multifaceted and interrelated. Future salt-reduction strategies should focus on the health benefits of reduced salt consumption and practical interventions such as salt alternatives and education on low-salt food choices and cooking methods and changing perceptions about salt reduction to become a social norm in the Chinese community.
Expression divergence of expansin genes drive the heteroblasty in Ceratopteris chingii
Authors: Zhang Yue , Van de Peer Yves , Lu Bei , Zhang Sisi , Che Jingru , Chen Jinming , Marchal Kathleen , Yang Xingyu
Published: November 2023

Background

Sterile-fertile heteroblasty is a common phenomenon observed in ferns, where the leaf shape of a fern sporophyll, responsible for sporangium production, differs from that of a regular trophophyll. However, due to the large size and complexity of most fern genomes, the molecular mechanisms that regulate the formation of these functionally different heteroblasty have remained elusive. To shed light on these mechanisms, we generated a full-length transcriptome of Ceratopteris chingii with PacBio Iso-Seq from five tissue samples. By integrating Illumina-based sequencing short reads, we identified the genes exhibiting the most significant differential expression between sporophylls and trophophylls.

Results

The long reads were assembled, resulting in a total of 24,024 gene models. The differential expressed genes between heteroblasty primarily involved reproduction and cell wall composition, with a particular focus on expansin genes. Reconstructing the phylogeny of expansin genes across 19 plant species, ranging from green algae to seed plants, we identified four ortholog groups for expansins. The observed high expression of expansin genes in the young sporophylls of C. chingii emphasizes their role in the development of heteroblastic leaves. Through gene coexpression analysis, we identified highly divergent expressions of expansin genes both within and between species.

Conclusions

The specific regulatory interactions and accompanying expression patterns of expansin genes are associated with variations in leaf shapes between sporophylls and trophophylls.
Determining the prognosis of Lung cancer from mutated genes using a deep learning survival model: a large multi-center study
Authors: Peng Jie , Xiao Lushan , Zhu Hongbo , Han Lijie , Ma Honglian
Published: November 2023

Background

Gene status has become the focus of prognosis prediction. Furthermore, deep learning has frequently been implemented in medical imaging to diagnose, prognosticate, and evaluate treatment responses in patients with cancer. However, few deep learning survival (DLS) models based on mutational genes that are directly associated with patient prognosis in terms of progression-free survival (PFS) or overall survival (OS) have been reported. Additionally, DLS models have not been applied to determine IO-related prognosis based on mutational genes. Herein, we developed a deep learning method to predict the prognosis of patients with lung cancer treated with or without immunotherapy (IO).

Methods

Samples from 6542 patients from different centers were subjected to genome sequencing. A DLS model based on multi-panels of somatic mutations was trained and validated to predict OS in patients treated without IO and PFS in patients treated with IO.

Results

In patients treated without IO, the DLS model (low vs. high DLS) was trained using the training MSK-MET cohort (HR = 0.241 [0.213–0.273], P < 0.001) and tested in the inter-validation MSK-MET cohort (HR = 0.175 [0.148–0.206], P < 0.001). The DLS model was then validated with the OncoSG, MSK-CSC, and TCGA-LUAD cohorts (HR = 0.420 [0.272–0.649], P < 0.001; HR = 0.550 [0.424–0.714], P < 0.001; HR = 0.215 [0.159–0.291], P < 0.001, respectively). Subsequently, it was fine-tuned and retrained in patients treated with IO. The DLS model (low vs. high DLS) could predict PFS and OS in the MIND, MSKCC, and POPLAR/OAK cohorts (P < 0.001, respectively). Compared with tumor-node-metastasis staging, the COX model, tumor mutational burden, and programmed death-ligand 1 expression, the DLS model had the highest C-index in patients treated with or without IO.

Conclusions

The DLS model based on mutational genes can robustly predict the prognosis of patients with lung cancer treated with or without IO.
Association between the non-HDL-cholesterol to HDL- cholesterol ratio and abdominal aortic aneurysm from a Chinese screening program
Authors: Lin Wenhui , Luo Songyuan , Li Wei , Liu Jitao , Zhou Ting , Yang Fan , Zhou Dan , Liu Yuan , Huang Wenhui , Feng Yingqing , Luo Jianfang
Published: November 2023

Background

Abdominal aortic aneurysms (AAAs) can result in high mortality upon rupture but are usually undiagnosed because of the absence of symptoms in the early stage. Ultrasound screening is regarded as an impactful way to prevent the AAA-related death but cannot be performed efficiently; therefore, a target population, especially in Asia, for this procedure is lacking. Additionally, although dyslipidaemia and atherosclerosis are associated with AAA. However, it remains undetermined whether the non-high-density lipoprotein-cholesterol to high-density lipoprotein-cholesterol ratio (NHHR) is associated with AAA. Therefore, this study was aimed at examining whether NHHR is associated with AAA.

Method

A total of 9559 participants who underwent AAA screening at Guangdong Provincial People’s Hospital and through screening in two communities in Dongguan, from June 2019 to June 2021 joined in this screening program. The diagnosis of AAA was confirmed by the ultrasound examination of the abdominal aorta rather than any known or suspected AAA. Clinical and laboratory data of participants were collected. The participants were separated into a normal group and an AAA group according to the abdominal aortic status. To eliminate confounding factors, a propensity score matching (PSM) approach was utilized. The independent relationship between NHHR and AAA was assessed through the utilization of multivariable logistic regression analysis. In addition, internal consistency was evaluated through subgroup analysis, which controlled for significant risk factors.

Results

Of all the participants, 219 (2.29%) participants were diagnosed with AAA. A significant elevation in NHHR was identified in the AAA group when contrasted with that in the normal group (P < 0.001). As demonstrated by the results of the multivariable logistic regression analysis, AAA was independently associated with NHHR before (odds ratio [OR], 1.440, P < 0.001) and after PSM (OR, 1.515, P < 0.001). Significant extension was observed in the areas under the receiver operating characteristic curves (AUROCs) of NHHR compared to those of single lipid parameters before and after PSM. An accordant association between NHHR and AAA in different subgroups was demonstrated by subgroup analysis.

Conclusion

In the Chinese population, there is an independent association between NHHR and AAA. NHHR might be propitious to distinguish individuals with high risk of AAA.
TROP2-directed nanobody-drug conjugate elicited potent antitumor effect in pancreatic cancer
Authors: Xu Caili , Zhu Min , Wang Qian , Cui Jiajun , Huang Yuping , Huang Xiting , Huang Jing , Gai Junwei , Li Guanghui , Qiao Peng , Zeng Xian , Ju Dianwen , Wan Yakun , Zhang Xuyao
Published: November 2023

Background

Pancreatic cancer is a highly aggressive malignancy with limited treatment options and a poor prognosis. Trophoblast cell surface antigen 2 (TROP2), a cell surface antigen overexpressed in the tumors of more than half of pancreatic cancer patients, has been identified as a potential target for antibody–drug conjugates (ADCs). Almost all reported TROP2-targeted ADCs are of the IgG type and have been poorly studied in pancreatic cancer. Here, we aimed to develop a novel nanobody-drug conjugate (NDC) targeting TROP2 for the treatment of pancreatic cancer.

Results

In this study, we developed a novel TROP2-targeted NDC, HuNbTROP2-HSA-MMAE, for the treatment of TROP2-positive pancreatic cancer. HuNbTROP2-HSA-MMAE is characterized by the use of nanobodies against TROP2 and human serum albumin (HSA) and has a drug-antibody ratio of 1. HuNbTROP2-HSA-MMAE exhibited specific binding to TROP2 and was internalized into tumor cells with high endocytosis efficiency within 5 h, followed by intracellular translocation to lysosomes and release of MMAE to induce cell apoptosis in TROP2-positive pancreatic cancer cells through the caspase-3/9 pathway. In a xenograft model of pancreatic cancer, doses of 0.2 mg/kg and 1 mg/kg HuNbTROP2-HSA-MMAE demonstrated significant antitumor effects, and a dose of 5 mg/kg even eradicated the tumor.

Conclusion

HuNbTROP2-HSA-MMAE has desirable affinity, internalization efficiency and antitumor activity. It holds significant promise as a potential therapeutic option for the treatment of TROP2-positive pancreatic cancer.

Graphical Abstract
A novel prognostic prediction indicator in patients with acute pulmonary embolism: Naples prognostic score
Authors: Zhu Ning , Lin Shanhong , Cao Chao
Published: November 2023

Acute pulmonary embolism (APE) is a potentially fatal disease. Early risk stratification is essential to determining appropriate treatment. We aimed to investigate the predictive value of the Naples Prognostic Score (NPS) for 30-day all-cause mortality in patients with APE. In this retrospective analysis, 325 hospitalized patients with APE were divided into Groups 0 (n = 131), 1 (n = 153), and 2 (n = 41) according to the NPS. The primary outcome event was all-cause mortality during 30 days of follow-up from the day of admission. The correlation between NPS, clinical features, and outcomes in each group was evaluated. The patients were divided into two groups, survivor (n = 294) and nonsurvivor (n = 31), according to their prognosis. The results of the comparison between the three NPS groups revealed that patients with older age, faster heart rate, lower systolic blood pressure, low albumin and total cholesterol levels, high neutrophil to lymphocyte ratio (NLR), low lymphocyte-to-monocyte ratio (LMR), right heart dilatation, heart failure, malignancy, and lower extremity venous thrombosis had significantly higher 30-day all-cause mortality (P < 0.05). Area under the receiver operating characteristic curve (AUC) for NPS to predict all-cause death within 30 days in patients with APE was 0.780 (95% confidence interval [CI] = 0.678–0.855), with sensitivity being 80.6% (95% CI = 0.667–0.946) and specificity being 72.1% (95% CI = 0.670–0.772). Kaplan-Meier (KM) curves showed that Group 2 APE patients had the highest risk of all-cause mortality compared with the other two groups (log-rank test, P = 0.0004). Forest plot visualization using the Cox proportional hazard model showed a significant increase in the risk of 30-day all-cause mortality by 239% (hazard ratio [HR] = 3.385 [1.115–10.273], P = 0.031) and 338% (HR = 4.377 [1.228–15.598], P = 0.023), and the trend test showed a statistical difference (P = 0.042). The study concluded that NPS is a novel, reliable, and multidimensional prognostic scoring system with good prediction of 30-day all-cause mortality in patients with APE.
Effect of online intervention mode on breastfeeding results: a systematic review and meta-analysis
Authors: Sun Yue , Gao Yutong , Zhu Zhiling , Zhu Lili
Published: November 2023

Objective

To evaluate the effect of Internet based intervention model on breastfeeding knowledge, attitude, self-confidence and breastfeeding rate.

Methods

An electronic literature search of PubMed, Embase, Web of Science, Cochrane Library, CINAHL, CNKI, Wanfang, CBM and VIP database was performed using combinations of the keywords “Breastfeeding,” “Breastfeeding, Exclusive,” “Internet,” “Online,” and “Website”. The retrieval period was from their inception to March 31, 2023. Quality appraisal was performed using the Cochrane 5.1 for randomized controlled trials (RCTs). RevMan5.3 was used for data analysis.

Results

Thirty-two studies were included in the review, with a total of 9514 samples. The results of Meta-analysis showed that, compared with routine nursing, the intervention model based on the Internet can effectively improve breastfeeding knowledge and attitude of pregnant women, improve breastfeeding self-confidence (P < 0.05), and improve the rate of exclusive breastfeeding in the short term (within 6 weeks) and the long-term postpartum (3–6 months) had a positive effect on the rate of exclusive breastfeeding (P < 0.05).

Conclusions

The Internet breastfeeding intervention model may be an effective intervention to improve the effect of exclusive breastfeeding. In the future, more high-quality, large-sample randomized controlled trials can be carried out to further explore the effect of the Internet intervention model on breastfeeding.
Inflammation and altered metabolism impede efficacy of functional electrical stimulation in critically ill patients
Authors: Jameson T. S. O. , Caldow M. K. , Stephens F. , Denehy L. , Lynch G. S. , Koopman R. , Krajcova A. , Urban T. , Berney S. , Duska F. , Puthucheary Z.
Published: November 2023

Background

Critically ill patients suffer from acute muscle wasting, which is associated with significant physical functional impairment. We describe data from nested muscle biopsy studies from two trials of functional electrical stimulation (FES) that did not shown improvements in physical function.

Methods

Primary cohort: single-centre randomized controlled trial. Additional healthy volunteer data from patients undergoing elective hip arthroplasty.Validation cohort: Four-centre randomized controlled trial.Intervention: FES cycling for 60-90min/day.Analyses: Skeletal muscle mRNA expression of 223 genes underwent hierarchal clustering for targeted analysis and validation.

Results

Positively enriched pathways between healthy volunteers and ICU participants were “stress response”, “response to stimuli” and “protein metabolism”, in keeping with published data. Positively enriched pathways between admission and day 7 ICU participants were “FOXO-mediated transcription” (admission = 0.48 ± 0.94, day 7 = − 0.47 ± 1.04 mean log2fold change;P = 0.042), “Fatty acid metabolism” (admission = 0.50 ± 0.67, day 7 = 0.07 ± 1.65 mean log2fold change;P = 0.042) and “Interleukin-1 processing” (admission = 0.88 ± 0.50, day 7 = 0.97 ± 0.76 mean log2fold change;P = 0.054). Muscle mRNA expression of UCP3 (P = 0.030) and DGKD (P = 0.040) decreased in both cohorts with no between group differences. Changes in IL-18 were not observed in the validation cohort (P = 0.268). Targeted analyses related to intramuscular mitochondrial substrate oxidation, fatty acid oxidation and intramuscular inflammation showed PPARγ-C1α; (P < 0.001), SLC25A20 (P = 0.017) and UCP3 (P < 0.001) decreased between admission and day 7 in both arms. LPIN-1 (P < 0.001) and SPT1 (P = 0.044) decreased between admission and day 7. IL-18 (P = 0.011) and TNFRSF12A (P = 0.009) increased in both arms between admission and day 7. IL-1β (P = 0.007), its receptor IL-1R1 (P = 0.005) and IL-6R (P = 0.001) decreased in both arms between admission and day 7. No between group differences were seen in any of these (all p > 0.05).

Conclusions

Intramuscular inflammation and altered substrate utilization are persistent in skeletal muscle during first week of critical illness and are not improved by the application of Functional Electrical Stimulation-assisted exercise. Future trials of exercise to prevent muscle wasting and physical impairment are unlikely to be successful unless these processes are addressed by other means than exercise alone.
Alterations to DNA methylation patterns induced by chemotherapy treatment are associated with negative impacts on the olfactory pathway
Authors: Ho Peh Joo , Khng Alexis Jiaying , Tan Benita Kiat-Tee , Lim Geok Hoon , Tan Su-Ming , Tan Veronique Kiak Mien , Tan Ryan Shea Ying Cong , Lim Elaine Hsuen , Iau Philip Tsau-Choong , Chew Ying Jia , Lim Yi Ying , Hartman Mikael , Tan Ern Yu , Li Jingmei
Published: November 2023

Background

Exposure to cytotoxic chemotherapy treatment may alter DNA methylation (DNAm) in breast cancer patients.

Methods

We performed DNAm analysis in 125 breast cancer patients with blood drawn before and after chemotherapy, using the Illumina MethylationEPIC array. DNAm changes of 588,798 individual CpGs (including 41,207 promoter regions) were evaluated using linear regression models adjusted for monocyte proportion. Gene set enrichment analyses (GSEA) were conducted to identify key Gene Ontology (GO) biological processes or Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with chemotherapy. Results were validated in a separate cohort of breast cancer patients who were treated (n = 1273) and not treated (n = 872) by chemotherapy (1808 blood, 337 saliva).

Results

A total of 141 differentially methylated CpGs and 11 promoters were significantly associated with chemotherapy after multiple testing corrections in both the paired sample and single time point analyses. GSEA of promoter regions (pre-ranked by test statistics) identified six suppressed biological processes (p < 4.67e−8) related to sensory perception and detection of chemical stimuli, including smell perception (GO:0007606, GO:0007608, GO:0009593, GO:0050906, GO:0050907, and GO:0050911). The same six biological processes were significantly suppressed in the validation dataset (p < 9.02e−14). The KEGG pathway olfactory transduction (hsa04740) was also found to be significantly suppressed (ppaired-samples = 1.72e−9, psingle-timepoint-blood = 2.03e−15 and psingle-timepoint-saliva = 7.52e−56).

Conclusion

The enrichment of imprinted genes within biological processes and pathways suggests a biological mechanism by which chemotherapy could affect the perception of smell.
The chromatin landscape of the euryarchaeon Haloferax volcanii
Authors: Marinov Georgi K. , Bagdatli S. Tansu , Wu Tong , He Chuan , Kundaje Anshul , Greenleaf William J.
Published: November 2023

Background

Archaea, together with Bacteria, represent the two main divisions of life on Earth, with many of the defining characteristics of the more complex eukaryotes tracing their origin to evolutionary innovations first made in their archaeal ancestors. One of the most notable such features is nucleosomal chromatin, although archaeal histones and chromatin differ significantly from those of eukaryotes, not all archaea possess histones and it is not clear if histones are a main packaging component for all that do. Despite increased interest in archaeal chromatin in recent years, its properties have been little studied using genomic tools.

Results

Here, we adapt the ATAC-seq assay to archaea and use it to map the accessible landscape of the genome of the euryarchaeote Haloferax volcanii. We integrate the resulting datasets with genome-wide maps of active transcription and single-stranded DNA (ssDNA) and find that while H. volcanii promoters exist in a preferentially accessible state, unlike most eukaryotes, modulation of transcriptional activity is not associated with changes in promoter accessibility. Applying orthogonal single-molecule footprinting methods, we quantify the absolute levels of physical protection of H. volcanii and find that Haloferax chromatin is similarly or only slightly more accessible, in aggregate, than that of eukaryotes. We also evaluate the degree of coordination of transcription within archaeal operons and make the unexpected observation that some CRISPR arrays are associated with highly prevalent ssDNA structures.

Conclusions

Our results provide the first comprehensive maps of chromatin accessibility and active transcription in Haloferax across conditions and thus a foundation for future functional studies of archaeal chromatin.
A gist on an obscure neoplasm in Ghana: gastrointestinal stromal tumours
Authors: Yorke Joseph , Brenu Samuel Gyasi , Awoonor-Williams Ronald , Tabiri Stephen , Seidu Anwar Sadat , Yamoah Francis Akwaw , Akpaloo Joseph , Der Edmund Muonir , Adjei Ernest , Okyere Isaac , Ihekanandu Kenneth Kelechi , Bonsu Ernest Bawuah Osei , Kyei Ishmael , Mensah Samuel , Adinku Michael Ofoe , Yorke Dennis Afful , Agyapong Akwasi Opoku , Aitpillah Francis Somiah-Kwaw , Agyei Martin Kofi , Oppong-Nkrumah Nana Akosua , Annan Kwasi Dadzie , Ellis Theodora-Ann Fremponma , Danso Patrick , Buckman Tonnies Abeku , Acheampong Emmanuel
Published: November 2023

Background

Gastrointestinal Stromal Tumour is a rare but potentially curable tumour of the gastrointestinal tract accounting for up to 1% of all gastrointestinal tumours. The discovery of Imatinib mesylate, a novel tyrosine kinase inhibitor has improved the chances even for unresectable, recurrent, or metastatic diseases.

Methods

This study sought to document the clinical and pathological characteristics of GISTs from two tertiary hospitals in Ghana that have undergone immunohistochemistry confirmation between 2014 and 2021.

Results

The median age of the subjects was 50 years with most of them (28.0%) being above 61 years. There were more females than males (64.0% vs. 36.0%). Abdominal mass and abdominal pain made up the majority of the clinical presentations. The majority of the subjects had partial gastrectomy (32.0%) which was followed by wedge resection (28.0%). Appendectomy and sleeve gastrectomy were the least performed procedures (8% each). Four of the 25 patients (16.0%) had resections of involved contiguous organs done with splenectomy being the most common procedure. The majority of GISTs were found in the stomach (68.0%) followed by the appendix (12.0%) and small bowel (12.0%). Gastrointestinal bleeding (55.8%) and abdominal pain (38.5%) were the most reported symptoms. Free resection margins were observed in 84.0% of the subjects and only 3/25 (12.0%) experienced tumour recurrence.

Conclusion

GIST is a potentially curable tumour that once was obscure but currently gaining popularity. Surgical resection offers the hope of a cure for localized disease while targeted therapies is a viable option for recurrent, metastatic, or unresectable tumours.
Safety and effectiveness of the Canadian food ladders for children with IgE-mediated food allergies to cow’s milk and/or egg
Authors: Chomyn Alanna , Chan Edmond S. , Yeung Joanne , Cameron Scott , Chua Gilbert T. , Vander Leek Timothy K. , Williams Brock A , Soller Lianne , Abrams Elissa M. , Mak Raymond , Wong Tiffany
Published: November 2023

Background

Food ladders are tools designed to facilitate home-based dietary advancement in children with food allergies through stepwise exposures to increasingly allergenic forms of milk and egg. Several studies have now documented safety and efficacy of food ladders. In 2021, we published a Canadian adaptation of the previously existing milk and egg ladders originating in Europe using foods more readily available/consumed in Canada. Our study adds to the growing body of evidence supporting food ladder use and provides safety and effectiveness data for our Canadian adaptation of the milk and egg ladders.

Methods

Surveys were distributed to families of children using the Canadian Milk Ladder and/or the Canadian Egg Ladder at baseline, with follow up surveys at 3 months, 6 months, and 12 months. Data were analyzed using REDCap and descriptive and inferential statistics are presented.

Results

One hundred and nine participants were started on milk/egg ladders between September 2020 and June 2022. 53 participants responded to follow up surveys. Only 2 of 53 (3.8%) participants reported receiving epinephrine during the study. Severe grade 4 reactions (defined according to the modified World Allergy Organization grading system) were not reported by any participants. Minor cutaneous adverse reactions were common, with about 71% (n = 10/14) of respondents reporting cutaneous adverse reactions by 1 year of food ladder use. An increasing proportion of participants could tolerate most foods from steps 2–4 foods after 3, 6, and 12 months of the food ladder compared to baseline.

Conclusion

The Canadian food ladders are safe tools for children with cow’s milk and/or egg allergies, and participants tolerated a larger range of foods with food ladder use compared to baseline.
Generalizable attention U-Net for segmentation of fibroglandular tissue and background parenchymal enhancement in breast DCE-MRI
Authors: Nowakowska Sylwia , Borkowski Karol , Ruppert Carlotta M. , Landsmann Anna , Marcon Magda , Berger Nicole , Boss Andreas , Ciritsis Alexander , Rossi Cristina
Published: November 2023

Objectives

Development of automated segmentation models enabling standardized volumetric quantification of fibroglandular tissue (FGT) from native volumes and background parenchymal enhancement (BPE) from subtraction volumes of dynamic contrast-enhanced breast MRI. Subsequent assessment of the developed models in the context of FGT and BPE Breast Imaging Reporting and Data System (BI-RADS)-compliant classification.

Methods

For the training and validation of attention U-Net models, data coming from a single 3.0-T scanner was used. For testing, additional data from 1.5-T scanner and data acquired in a different institution with a 3.0-T scanner was utilized. The developed models were used to quantify the amount of FGT and BPE in 80 DCE-MRI examinations, and a correlation between these volumetric measures and the classes assigned by radiologists was performed.

Results

To assess the model performance using application-relevant metrics, the correlation between the volumes of breast, FGT, and BPE calculated from ground truth masks and predicted masks was checked. Pearson correlation coefficients ranging from 0.963 ± 0.004 to 0.999 ± 0.001 were achieved. The Spearman correlation coefficient for the quantitative and qualitative assessment, i.e., classification by radiologist, of FGT amounted to 0.70 (p < 0.0001), whereas BPE amounted to 0.37 (p = 0.0006).

Conclusions

Generalizable algorithms for FGT and BPE segmentation were developed and tested. Our results suggest that when assessing FGT, it is sufficient to use volumetric measures alone. However, for the evaluation of BPE, additional models considering voxels’ intensity distribution and morphology are required.

Critical relevance statement

A standardized assessment of FGT density can rely on volumetric measures, whereas in the case of BPE, the volumetric measures constitute, along with voxels’ intensity distribution and morphology, an important factor.

Key points

• Our work contributes to the standardization of FGT and BPE assessment.

• Attention U-Net can reliably segment intricately shaped FGT and BPE structures.

• The developed models were robust to domain shift.

Graphical Abstract