bluuebunny/crossref_metadata_2025 huggingface dataset:
Physical activity levels among undergraduate students at the College of Applied Medical Sciences, King Saud University, Riyadh: A prevalence study
Authors: Alhammad Saad A. , Almutairi Faisal M. , Bajsair Abdulaziz S. , Alghamdi Abdulrahman S. , Algarni Fahad S. , Aldaihan Mishal M. , Alshehri Waleed M. , Alwadeai Khalid S.
Published: December 2023

Physical inactivity and sedentary behavior pose significant health concerns, particularly among young adults like college students. However, little research exists on the attitudes towards physical activity among Saudi Arabian healthcare students. This study aimed to assess the prevalence of physical activity and determine the reason for being physically inactive among students and interns across all programs in the College of Applied Medical Sciences (CAMS) at King Saud University (KSU), Riyadh, Saudi Arabia. A cross-sectional online survey was conducted between March and May 2023. CAMS students aged 18 and above, fluent in Arabic or English, and willing to participate were included. The Global Physical Activity Questionnaire (GPAQ) was used to measure physical activity. Descriptive statistics were used for data analysis. Out of 433 respondents, 377 met the inclusion criteria (response rate: 89.3%). Physical activity prevalence was 54.60%, with walking being the most common activity (42.70%). Lack of time was the primary reason for inactivity (51.40%). On average, students engaged in 1.5 hours/day of vigorous-intensity activities and 1.3 hours/day of vigorous-intensity sports and fitness activities at work. Sedentary behavior, characterized by continuous sitting, averaged 5.37 hours per day. Approximately half of CAMS students are physically active, while 20% rely solely on short walks due to time constraints, limited activity hours, or sedentary habits. A lack of time was cited as the primary reason for inactivity by most students. Future research should focus on strategies to enhance physical activity among healthcare students. In addition, academicians and policymakers should propose time-efficient initiatives that accommodate the demanding and busy schedules of healthcare students.
Construction and validation of a nomogram prediction model for postoperative incisional infection in ankle fractures
Authors: Deng Guang-Hua
Published: December 2023

The aim was to investigate the independent risk factors for postoperative incisional infection in ankle fractures and to establish a nomogram prediction model accordingly. Data were collected from ankle fracture patients in the Affiliated Hospital of Xinjiang Medical University from January 2018 to December 2022. Univariate and multivariate logistic regression analyses were used to determine the independent risk factors for postoperative incisional infection in ankle fractures and to establish the corresponding nomogram. Receiver operating characteristic curves were plotted and area under the curve was calculated, and calibration curves and decision curve analysis were plotted to evaluate the model performance. A total of 722 patients with ankle fractures were included in the study, and 76 patients developed postoperative incisional infections, with an incidence of 10.53%. After univariate and multivariate logistic regression analysis, a total of 5 variables were identified as independent risk factors for postoperative incisional infection in ankle fractures, namely, age ≥ 60 years (OR, 1.885; 95% CI, 1.156–3.045), having diabetes (OR1.625; 95% CI, 1.095–2.876), open fracture (OR, 5.564; 95% CI, 3.099–9.990), albumin < 35 g/L (OR, 2.618; 95% CI, 1.217–4.215), and operative time ≥ 2 hours (OR, 1.606; 95% CI, 1.077–3.247). The nomogram for postoperative incisional infection after ankle fracture constructed in this study has good predictive accuracy and helps orthopedic surgeons to intervene earlier in patients at high risk of postoperative incisional infection after ankle fracture.
Estimating surgical probability: Development and validation of a prognostic model for patients with lumbar disc herniation treated with acupuncture
Authors: Chen Di , Lv Zimeng , Wu Yicheng , Hao Panfu , Liu Liu , Pan Bin , Shi Haiping , Che Youlu , Shen Bo , Du Peng , Si Xiaohua , Hu Zhongling , Luan Guorui , Xue Mingxin
Published: December 2023

Lumbar disc herniation (LDH) is a common cause of pain in the lumbar spine and legs. While acupuncture has become the primary conservative treatment for LDH, some patients experience treatment failure and require surgery, causing substantial concern for clinicians. We developed an effective personalized clinical prediction model to identify the independent risk factors associated with acupuncture failure in patients with LDH. Our model aimed to predict the probability of surgery within 6 months of acupuncture failure in patients with LDH. A total of 738 patients with LDH who underwent acupuncture at 4 Chinese hospitals between January 2019 and October 2021 were selected. The patients were divided into training (n = 496) and validation (n = 242) cohorts. Seven predictive variables, including smoking, Oswestry Disability Index (ODI) score, lower-limb herniation, disc herniation type, lumbar spinal stenosis, lumbar lateral recess stenosis, and acupuncture frequency, were selected as risk factors using least absolute shrinkage and selection operato (LASSO) regression. A prediction model was developed using multivariate logistic regression analysis and a nomogram was constructed. The model exhibited good discrimination, with an area under the ROC curve (AUC) of 0.903 for the development cohort and 0.899 for the validation cohort. The Hosmer-Lemeshow goodness-of-fit test was a good fit for both cohorts (P = .956 for the development cohort; P = .513 for the validation cohort). Decision curve analysis (DCA) demonstrated that the threshold probabilities for the 2 cohorts ranged from > 4% and 5–95%, respectively. Therefore, the prediction model had a good net benefit. The nomogram established in this study, incorporating 7 risk factors, demonstrated a good predictive ability. It could predict acupuncture failure in LDH patients and the risk of surgery within 6 months, enabling physicians to conduct individualized treatment measures.
Expression and Functional Analysis of core stemness factors OSKM (OCT4, SOX2, KLF4, and MYC) in Pan-cancer
Authors: Hong Liwei , Hong Sijie , Zhang Xueqin
Published: December 2023

The dedifferentiation process of tumorigenesis and somatic cell reprogramming has some commonness and differences, which is the key question to cancer therapeutic strategy and stem cell applications. To further explore the commonalities and variance between carcinogenesis and induced pluripotent stem cell reprogramming, we investigated the role of stemness factors OSKM (OCT4, SOX2, KLF4, and MYC) in the pan-cancer process using public clinical data. Expression of OSKM in human pan-cancer was analyzed via the Genotype Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) database based on the RNA-seq data of tissues. The correlation of expression between OSKM genes was analyzed via the Tumor Immune Evaluation Resource (TIMER) database, while the STRING tool was used to construct the protein-protein interaction network for OSKM. Prognostic impact of OSKM in pan-cancer was analyzed by Cox proportional hazards regression model. The relationships between OSKM and tumor stemness, tumor microenvironment and immune checkpoint and were performed by Sangerbox platform using Pearson correlation analysis. Our results showed that OSKM were universally expressed and significantly altered in tumors compared with adjacent normal tissues in most tumor types. In addition, correlation analysis revealed the relevance of OSKM genes to patient prognosis, cancer cell stemness, tumor microenvironment or immune checkpoint. However, there is little similarity between these genes in terms of how they function in each cancer type. This study elucidates the different roles of core stemness factors OSKM in pan-cancer, offering potential therapeutic targets for novel anti-cancer strategies and knowledge to minimize the potential carcinogenic effects during stem cell transplantation.
Intelectin-1 is a novel prognostic biomarker for hepatocellular carcinoma
Authors: Li Jiang , Tao Hai-Su , Yuan Tong , Huang Zhi-Yong , Zhang Er-Lei
Published: December 2023

The molecular mechanisms of hepatocellular carcinoma (HCC) are still not well understood. Gene microarray analysis showed that the expression of Intelectin-1 (ITLN-1) in tumor-adjacent normal liver tissue was 454.8 times higher than in the corresponding cancer tissue. ITLN-1 is a secreted soluble glycoprotein which has been reported to be associated with the occurrence and development of various tumor types. However, the prognostic significance of ITLN-1 in HCC remain unclear. Real-time fluorescence quantitative polymerase chain reaction was used to investigate 149 liver cancer cases for ITLN-1 mRNA expression. Immunohistochemistry and western blot analysis were used to ascertain protein expression of ITLN-1 in cancer and para-carcinomatous tissue, and further to evaluate the correlation between ITLN-1 mRNA expression and surgical prognosis after liver resection. The ITLN-1 mRNA and protein levels were significantly higher in adjacent normal liver tissues than HCC tissues. Real-time fluorescence quantitative polymerase chain reaction showed that the ITLN-1 expression was decreased in 78.5% (117/149) of HCC tissues compared with their corresponding adjacent liver tissues. Moreover, its low expression was significantly correlated with increased tumor size, tumor differentiation degree, degree of liver cirrhosis, capsule integrity, vascular invasion and tumor recurrence. Patients with high ITLN-1 expression had significantly better overall and recurrence-free survival after curative liver resection. Multivariate cox regression analysis showed that ITLN-1 was an independent predictor of surgical outcomes in HCC patients. The present study suggested that low ITLN-1 expression was associated with poor clinical outcome for HCC patients, indicating a novel biomarker for prognosis evaluation and a potential therapeutic target for HCC patients.
Analysis of the antibacterial effects of turmeric on particular bacteria
Authors: Odo Edward Odogbu , Ikwuegbu Josephine Adaku , Obeagu Emmanuel Ifeanyi , Chibueze Silas Andrew , Ochiaka Raphael E.
Published: December 2023

Antimicrobial properties of plants have been investigated by a number of studies worldwide and many of them have been used as therapeutic alternatives because of their antimicrobial properties. The quest for suitable and affordable alternative in the face of increasing antimicrobial drug resistant has led researchers into exploring the use of plant extract in the treatment of infections. The antibacterial properties of turmeric (Curcuma longa) on selected bacteria were evaluated. Different concentrations of turmeric extract (100, 50, 25, and 12.5 mg/mL) were prepared using 2 solvents namely water and ethanol. The antibacterial activity was tested against Bacillus species, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa at different concentration of the extract using disc diffusion method and ciprofloxacin was the control. The zones of inhibition exhibited by ethanol and aqueous extracts against test organisms ranged from 1 to 10 mm. the ethanolic extracts were more effective than the aqueous extracts exhibiting zones of inhibition ranging from 3 to 10 mm against Bacillus species, 4 to 9 mm against S aureus, and 1 to 7 mm against E coli. There was no inhibitory effect against P aeruginosa. There was significant difference between the ethanol and aqueous extracts (P < .05). This study reveal that Turmeric plant has antibacterial potential against selected organisms and may be of great use of pharmaceutical industries for the development of medicine to cure ailments and control abnormal serum lipid profile.
Comprehensive review of aortic aneurysms, dissections, and cardiovascular complications in connective tissue disorders
Authors: Elendu Chukwuka , Amaechi Dependable C. , Elendu Tochi C. , Ibhiedu Jennifer O. , Torubiri Augustina O. , Okoye Osinachi K.
Published: December 2023

Connective tissue disorders, including Marfan syndrome (MS) and Ehlers-Danlos syndrome (EDS), are characterized by genetic mutations affecting connective tissue structural integrity. These disorders significantly elevate the risk of aortic dissection, a life-threatening condition. This comprehensive review delves into the intricate interplay between connective tissue disorders and aortic dissection, shedding light on the clinical features, pathophysiology, genetic underpinnings, diagnostic approaches, clinical management, associated comorbidities, and prognosis, mainly focusing on MS and EDS, while also exploring rare connective tissue disorders and forms of cutis laxa contributing to aortic pathology.
Endocrine features of primary mitochondrial diseases
Authors: Romo Lindsay , Gold Nina B. , Walker Melissa A.
Published: December 2023

Purpose of review

Primary mitochondrial diseases are one of the most prevalent groups of multisystem genetic disorders. Endocrinopathies associated with mitochondrial diseases may have clinical features that are distinct from the more common forms. We provide an overview of mitochondrial disorder genetics and phenotypes, focusing on recent studies regarding identification and treatment of associated endocrinopathies.

Recent findings

Known endocrine phenotypes of mitochondrial disorders continue to expand, and now include growth hormone deficiency, hypogonadism, precocious puberty, hypoparathyroidism, hypo- and hyperthyroidism, diabetes, and adrenal insufficiency. Recent studies suggest several genotype-phenotype correlations, including those related to nuclear variants. Diagnosis is important, as special considerations should be made in the management of endocrinopathies in mitochondrial patients. Finally, new mitochondrial replacement strategies may soon be available for women interested in preventing mitochondrial disease transmission to offspring.

Patients with multiple endocrinopathies or atypical endocrinopathies should be evaluated for primary mitochondrial disease, as a diagnosis may impact management of these individuals.
Interaction between dietary flavonoid intake and trouble sleeping on non-alcoholic fatty liver disease risk: a cross-sectional study
Authors: Yang Xinxia , Zhuo Shitu , Fang Taiyong
Published: December 2023

Objective

The possible interaction of dietary flavonoid intake and sleep on non-alcoholic fatty liver disease (NAFLD) has not been well studied. This study investigated the interaction between dietary flavonoid intake and trouble sleeping on the risk of NAFLD.

Methods

Three discrete National Health and Nutrition Examination Survey data cycles from 2007 to 2010 and 2017 to 2018 were used. NAFLD was diagnosed by a US Fatty Liver Index ≥30. A sleep questionnaire diagnosed trouble sleeping. Univariate and multivariate logistic regression, restricted cubic spline (RCS) and subgroup analyses were used to evaluate the association between dietary flavonoids, trouble sleeping and NAFLD. We employed the relative excess risk due to interaction, attributable proportion of interaction and synergy index to evaluate additive interactions.

Results

Ultimately, 5056 participants were enrolled, and higher anthocyanidins and flavanones intake was negatively correlated with NAFLD. Conversely, trouble sleeping was positively associated with NAFLD. These correlations remained stable after adjusting for confounders, and there was a sex difference in this relationship. In the RCS model, anthocyanins were negatively non-linearly related to NAFLD, while flavanones showed a negative linear relationship. Moreover, there was a synergistic interplay between low dietary anthocyanin intake and trouble sleeping on the risk of NAFLD. A similar relationship existed for flavanone intake.

Conclusion

Anthocyanin and flavanone intake were negatively associated, whereas trouble sleeping was positively associated with NAFLD risk. There was a synergistic effect of low anthocyanin intake and trouble sleeping. The same relationship existed for low flavanone intake.
Association of BMI with mortality in drug-induced liver injury
Authors: Ma Zikun , Li Min , Wang Yan , Zou Cailun , Wang Yu , Guo Tiantian , Su Yu , Zhang Mengmeng , Meng Yao , Jia Jidong , Zhang Jing , Zou Zhengsheng , Zhao Xinyan
Published: December 2023

Background

To clarify the associations between BMI and the incidences of all-cause death or liver-related death (LRD)/liver transplantation (LT) in drug-induced liver injury (DILI).

Methods

DILI patients from three hospitals were retrospectively retrieved and follow-up from 2009 to 2021. They were categorized into underweight (BMI < 18.5 kg/m2), normal weight (BMI of 18.5–23.9 kg/m2), overweight (BMI of 24–27.9 kg/m2) and obese (BMI ≥ 28 kg/m2) groups. Cox regression models were conducted to reveal the effect of BMI on all-cause death or LRD/LT.

Results

A total of 1469 eligible DILI patients were included: underweight 73 (4.97%), normal weight 811 (55.21%), overweight 473 (32.20%) and obese 112 (7.62%). Eighty-nine patients (6.06%) had all-cause death, of which 66 patients (4.49%) had LRD/LT. The median age was 52 years old, and females were 1039 (70.73%). The associations between BMI and all-cause mortality (nonlinear test P < 0.01) or liver-related mortality/LT (nonlinear test P = 0.01) were J-shaped. Multivariate Cox regression analysis showed that underweight (HR: 3.02, 95% CI: 1.51–6.02) was significantly associated with all-cause mortality after adjusting for age and sex. Furthermore, obese males were significantly associated with liver-related mortality/LT (HR: 3.49, 95% CI: 1.13–10.72) after additional adjustment for serological indices and comorbidities.

Conclusion

Association between BMI and mortality is a J-shape. The overall mortality was significantly higher in underweight and obese group. Male obesity is independently associated with LRD/LT. These findings indicate that DILI patients with extreme BMI would have a high risk of dismal outcomes, which warrants extra medical care.
Paroxysmal atrial fibrillation and hemochromatosis: a narrative review
Authors: Ahmed Gulzar , Rathi Sushma , Sidhu Harmandeep K. , Muzaffar Momil , Wajid Muhammad H. , Kumari Komal , Fakhor Hajar , Attia Nada M. , Majumder Koushik , Kumar Vikash , Tejwaney Usha , Ram Nanik
Published: December 2023

Paroxysmal atrial fibrillation (PAF) and hemochromatosis have a complex relationship. This review explores its mechanisms, prevalence, correlations, and clinical manifestations. Hereditary hemochromatosis (HH) involves iron overload due to HFE protein mutations, while atrial fibrillation (AF) is characterized by irregular heart rhythms. Iron overload in hemochromatosis can promote cardiac arrhythmias. AF is prevalent in developed countries and may be linked to cryptogenic strokes. Genetic variations and demographic factors influence the occurrence of both conditions. HH affects multiple organ systems, including the heart, while AF causes palpitations and reduced exercise tolerance. Diagnosis involves iron markers, genotypic testing, and electrocardiogram (ECG) findings. Treatment strategies focus on reducing iron levels in hemochromatosis and managing AF through antithrombotic therapy and rhythm control. Untreated hemochromatosis carries a higher risk of complications, and PAF is associated with increased cardiovascular-related mortality. For better understanding of the mechanisms and to improve management, additional studies are required. Tailored approaches and combined treatments may enhance patient outcomes.
Coronavirus Disease 2019 Infection in Cervical Artery Dissections
Authors: Wahood Waseem , Flemming Kelly D. , Lanzino Giuseppe , Keser Zafer
Published: December 2023

Objective:

Most cervical artery dissection (CeAD) cases are spontaneous or due to minor traumas, and preceding viral infections have been suggested to be a triggering event for CeAD in some. Herein, we analyze the prevalence of coronavirus disease 2019 (COVID-19) in hospitalized patients with CeAD using a national database.

Methods:

The National Inpatient Sample was queried from April 2020 to December 2020 for patients with a diagnosis of CeAD using International Classification of Diseases, 10th edition-Clinical Modification codes. Among these, patients with COVID-19 were identified. Multivariable logistic regression was conducted to assess the patient profile of those with COVID-19, in-patient mortality, and home discharge among patients with CeAD.

Results:

There were 360 (2.32%) hospitalizations involving COVID-19 among 15,500 with CeAD. Concomitant acute ischemic stroke constituted 43.06% of those with a COVID-19 diagnosis, whereas it was 43.73% among those without a COVID-19 diagnosis (P = 0.902). Home discharges were less common in patients with COVID-19 and CeAD compared to CeAD alone (34.85% vs. 48.63%; P = 0.03), but this was likely due to other factors as multivariate regression analysis did not show an association between COVID-19 and home discharges (odds ratio: 0.69; 95% CI: 0.39 to 1.25; P = 0.22). COVID-19 diagnosis had similar odds of inpatient mortality (odds ratio: 1.11; 95% CI: 0.43 to 2.84; P = 0.84).

Conclusion:

The prevalence of COVID-19 among hospitalized patients with CeAD is low with 2.32% of all CeAD cases. Concomitant COVID infection did not lead to an increased risk of stroke in CeAD. However, potentially worse functional outcomes (fewer home discharges) without an increase in mortality were seen in patients with COVID and CeAD.
An overview of the physiopathology and various treatment strategies for polycystic ovary syndrome
Authors: Rajabi Ayda , Babaie Soraya , Sadeghzadeh Oskouei Behnaz , Mehdizadeh Amir , Farshbaf-Khalili Azizeh
Published: December 2023

Polycystic ovary syndrome (PCOS), a common endocrine disorder with metabolic and reproductive consequences, affects a significant percentage of women of reproductive age. Because of its complexity and impact on the quality of life, PCOS requires timely diagnosis and screening for complications. The most common clinical manifestations of PCOS are hirsutism, hyperandrogenism, acne, irregular cycles, amenorrhea, and anovulation. Although PCOS has different clinical manifestations in women, hyperandrogenism, and anovulation are the most common symptoms. A good medical history, examination, blood tests, and ultrasound findings facilitate the diagnosis of PCOS. Novel treatments have also undergone clinical trials to improve the symptoms of PCOS. However, comprehensive review articles investigating the different communities of this disease are limited, and this review aimed to collect data on the different etiologies of PCOS along with the latest diagnostic methods and the most common and up-to-date treatments for this disease.
Microcystic Serous Cystadenoma Masquerading as Pancreatic Neuroendocrine Tumor on 99mTc-HYNIC-TOC SPECT/CT
Authors: Cai Wenjiao , Dong Yiyuan , Zhao Tingting , Dong Aisheng , Zhao Qian
Published: December 2023

We present 99mTc-HYNIC-TOC SPECT/CT findings in a case of microcystic serous cystadenoma of the pancreatic head. The pancreatic tumor showed intense 99mTc-HYNIC-TOC uptake mimicking neuroendocrine tumor on SPECT/CT. This case indicates that microcystic serous cystadenoma should be included in the differential diagnosis of 99mTc-HYNIC-TOC–avid pancreatic masses.
Relationship between Blood Group (ABO) and Risk of COVID-19 Infection in a Patient Cohort in Tehran, Iran
Authors: Fathollahi Asal , bashizadeh fakhar haniyeh , Shaghaghi Babak
Published: December 2023

Background and purpose: Coronavirus (COVID-19) is a contagious disease causing severe acute respiratory syndrome which had a catastrophic effect on the world population and resulted in more than 2.9 million deaths worldwide. Epidemiological investigations have recently announced blood type has an association with the incidence of COVID-19 infection. Consequently, research in this regard can be effective in determining a person's susceptibility to a viral infection. Therefore, we investigated the relationship between blood types and the risk of COVID-19 in patients admitted to Khorshid laboratory, Tehran, Iran.
Materials and methods: From January to March 2020, 50 nasal and throat swap samples of patients’ secretions were obtained from patients who were admitted to Khorshid laboratory. They were confirmed to have COVID-19 virus RNA and real-time polymerase chain reaction (PCR)-ABI, and their blood type was determined simultaneously. After collecting data to determine the relationship between COVID-19 infection and blood type, a confidence interval of 90% was considered using SPSS 16.
Results: The mean age of the patients was measured at 38.4±6.3 years. According to PCR results, 100% of the subjects with COVID-19 showed blood type A. In addition, the ratio of blood type A to the percentage of reference type O was higher (P=0.009).
Conclusion: There was a significant relationship between ABO blood type and susceptibility to COVID-19. As the current study suggests, those with blood type A are at a higher COVID-19 infection risk than those with blood type O.
Williamsia muralis bacteraemia in a patient with Fanconi anaemia after haematopoietic cell transplantation
Authors: Sonoda Motoshi , Motomura Yoshitomo , Ishimura Masataka , Kanno Shunsuke , Kiyosuke Makiko , Ohga Shouichi
Published: December 2023

Introduction.

Williamsia muralis

is an environmental bacterium first detected in 1999. Infections with

W. muralis

isolated have been reported in two elderly patients, and were associated with the surgical intervention of artificial objects. We present a case of bacteraemia caused by

W. muralis

following haematopoietic cell transplantation (HCT).

Case presentation. A 10-year-old Japanese boy presented with fever and the swelling of the left cheek 8 days after HCT for the treatment of Fanconi anaemia. Gram-positive, rod-shaped bacteria were isolated from the blood cultures after 5 days incubation. 16S rRNA sequencing, but not mass spectrometry, identified a strain of

W. muralis

(1 414 bp, %ID 100 %). The phlegmon did not respond to antimicrobial therapy, but remitted with defervescence after a successful engraftment with teicoplanin and meropenem therapy on day 16 after HCT. The patient experienced recurrence of the bacteraemia, leading to central venous catheter (CVC) line removal. The same strain of

W. muralis

was isolated from the cultured tip of the CVC. To our knowledge, this is the first reported case of

W. muralis

bacteraemia and was complicated by CVC infection after HCT.

Conclusion.

W. muralis

bacteraemia developed in an immunocompromised child. Introduction of artificial objects into the body raises a risk of rare infection with slowly growing environmental bacteria.
The Fracture Risk Assessment Tool Probability and Trabecular Bone Score Mediate the Relationship between Sphingosine 1-phosphate Levels and Fracture Risk
Authors: Lee Seung Hun , Kim Jae Seung , Koh Jung-Min
Published: December 2023

Background: The sphingosine 1-phosphate (S1P) concentration is a potential biomarker of osteoporotic fracture and is associated with both the fracture risk assessment tool (FRAX) probability and trabecular bone score (TBS), which are well-known predictors of fracture. We sought to estimate the effect of the S1P concentration on fracture risk using the FRAX probability and TBS as mediators.Methods: Plasma S1P concentrations, FRAX variables, and TBSs were measured in 66 postmenopausal women with fractures and 273 postmenopausal women without fractures. Associations between S1P concentration, FRAX probability, TBS, and fracture risk were analyzed using correlation, logistic regression, and mediation analyses.Results: Subjects in the highest S1P concentration tertile had a higher fracture risk (odds ratio [OR], 5.09; 95% confidence interval [CI], 2.22–11.67) than those in the lowest S1P concentration tertile before adjustment. Subjects in the highest FRAX probability tertile had a higher fracture risk (OR, 14.59; 95% CI, 5.01–42.53) than those in the lowest FRAX probability tertile before adjustment. Subjects in the lowest TBS tertile had a higher fracture risk (OR, 4.76; 95% CI, 2.28–9.93) than those in the highest TBS tertile before adjustment. After adjustment for FRAX probability and TBS, the highest S1P concentration tertile was still associated with a higher fracture risk (OR, 3.13; 95% CI, 1.28–7.66). The FRAX probability and TBS accounted for 32.6% and 21.7%, respectively, of the relationship between the S1P concentration and fracture risk.Conclusions: The relationship between the circulating S1P concentration and fracture risk was partly mediated by the FRAX probability, bone microarchitecture, and other factors.
A (Sub)field Guide to Quality Control in Hippocampal Subfield Segmentation on High-resolution T2-weighted MRI
Authors: Canada K.L. , Mazloum-Farzaghi N. , Rådman G. , Adams J.N. , Bakker A. , Baumeister H. , Berron D. , Bocchetta M. , Carr V. , Dalton M.A. , de Flores R. , Keresztes A. , La Joie R. , Mueller S.G. , Raz N. , Santini T. , Shaw T. , Stark C.E.L. , Tran T.T. , Wang L. , Wisse L.E.M. , Wuestefeld A. , Yushkevich P.A. , Olsen R.K. , Daugherty A.M.
Published: December 2023

Inquiries into properties of brain structure and function have progressed due to developments in magnetic resonance imaging (MRI). To sustain progress in investigating and quantifying neuroanatomical detailsin vivo, the reliability and validity of brain measurements are paramount. Quality control (QC) is a set of procedures for mitigating errors and ensuring the validity and reliability of brain measurements. Despite its importance, there is little guidance on best QC practices and reporting procedures. The study of hippocampal subfieldsin vivois a critical case for QC because of their small size, inter-dependent boundary definitions, and common artifacts in the MRI data used for subfield measurements. We addressed this gap by surveying the broader scientific community studying hippocampal subfields on their views and approaches to QC. We received responses from 37 investigators spanning 10 countries, covering different career stages, and studying both healthy and pathological development and aging. In this sample, 81% of researchers considered QC to be very important or important, and 19% viewed it as fairly important. Despite this, only 46% of researchers reported on their QC processes in prior publications. In many instances, lack of reporting appeared due to ambiguous guidance on relevant details and guidance for reporting, rather than absence of QC. Here, we provide recommendations for correcting errors to maximize reliability and minimize bias. We also summarize threats to segmentation accuracy, review common QC methods, and make recommendations for best practices and reporting in publications. Implementing the recommended QC practices will collectively improve inferences to the larger population, as well as have implications for clinical practice and public health.
GABA(A) receptor activation drives GABARAP-Nix mediated autophagy to radiation-sensitize primary and brain-metastatic lung adenocarcinoma tumors
Authors: Bhattacharya Debanjan , Barille Riccardo , Toukam Donatien Kamdem , Gawali Vaibhavkumar S. , Kallay Laura , Ahmed Taukir , Brown Hawley , Rezvanian Sepideh , Karve Aniruddha , Desai Pankaj B. , Medvedovic Mario , Wang Kyle , Ionascu Dan , Harun Nusrat , Wang Chenran , Baschnagel Andrew M. , Kritzer Joshua A. , Cook James M. , Pomeranz Krummel Daniel A. , Sengupta Soma
Published: December 2023

In non-small cell lung cancer (NSCLC) treatment, targeted therapies benefit only a subset of NSCLC, while radiotherapy responses are not durable and toxicity limits therapy. We find that a GABA(A) receptor activator, AM-101, impairs viability and clonogenicity of NSCLC primary and brain metastatic cells. Employing anex vivo‘chip’, AM-101 is as efficacious as the chemotherapeutic docetaxel, which is used with radiotherapy for advanced-stage NSCLC.In vivo, AM-101 potentiates radiation, including conferring a survival benefit to mice bearing NSCLC intracranial tumors. GABA(A) receptor activation stimulates a selective-autophagic response via multimerization of GABA(A) Receptor-Associated Protein (GABARAP), stabilization of mitochondrial receptor Nix, and utilization of ubiquitin-binding protein p62. A targeted-peptide disrupting Nix binding to GABARAP inhibits AM-101 cytotoxicity. This supports a model of GABA(A) receptor activation driving a GABARAP-Nix multimerization axis triggering autophagy. In patients receiving radiotherapy, GABA(A) receptor activation may improve tumor control while allowing radiation dose de-intensification to reduce toxicity.

Highlights

Activating GABA(A) receptors intrinsic to lung primary and metastatic brain cancer cells triggers a cytotoxic response.

GABA(A) receptor activation works as well as chemotherapeutic docetaxel in impairing lung cancer viabilityex vivo.

GABA(A) receptor activation increases survival of mice bearing lung metastatic brain tumors.

A selective-autophagic response is stimulated by GABA(A) receptor activation that includes multimerization of GABARAP and Nix.

Employing a new nanomolar affinity peptide that abrogates autophagosome formation inhibits cytotoxicity elicited by GABA(A) receptor activation.
Assessment of Socio-Demographic factors associated with the Utilization of Insecticide-Treated Nets (ITNs) Among Children Under-5 years old and Pregnant Women in Nigeria: A secondary analysis of NMIS data
Authors: Omole Emmanuel Babagbotemi , Ndukwe Olachi Sandra
Published: December 2023

Malaria remains a persistent global health challenge, particularly in sub-Saharan Africa, with Nigeria shouldering a disproportionate burden. Despite extensive interventions, insecticide-treated nets (ITNs) have emerged as a cost-effective tool in the World Health Organization’s malaria control strategy. Utilizing data from the 2021 Nigeria Malaria Indicator Survey, this study explores socio-demographic determinants influencing ITN utilization among specific cohorts—children under-5 years and pregnant women. Findings indicate that 56% of Nigerian households possessed at least one ITN, with significant utilization observed among rural households, households from the North West and North East geopolitical zones, and households in the second and lowest wealth quintiles (p<0.05). Only 41.2% of children under-5 years old slept under an ITN on the night before the survey, underscoring notable coverage gaps. Statistical analyses reveal significant associations (p< 0.05) between ITN usage and variables such as age, residence, geopolitical zone, and wealth quintile at both bivariate and multivariate analytical levels. ITN usage decreases with increasing child age and household wealth quintile. For pregnant women, almost half (50%) in all households slept under an ITN the night before the survey. At both bivariate and multivariate analytical levels, significant associations (p< 0.05) were observed between ITN usage among pregnant women and variables such as geopolitical zone and household wealth quintile. Additionally, at the multivariate level, ITN utilization decreases with increasing educational level. Our study reveals the dynamic nature of ITN usage patterns, necessitating ongoing monitoring and adaptive strategies to address regional and socioeconomic differentials, while sustaining awareness initiatives to meet the targets set by the Nigeria National Malaria Strategic Plan.
The immune landscape of the inflamed joint defined by spectral flow cytometry
Authors: Attrill Meryl H. , Shinko Diana , Alexiou Vicky , Kartawinata Melissa ,   CHARMS study,   JIAP study, Wedderburn Lucy R. , Pesenacker Anne M.
Published: December 2023

Cellular phenotype and function are altered in different microenvironments. For targeted therapies it is important to understand site-specific cellular adaptations. Juvenile Idiopathic Arthritis (JIA) is characterised by joint inflammation, with frequent inadequate treatment responses. To comprehensively assess the inflammatory immune landscape, we designed a 37-parameter spectral flow cytometry panel delineating mononuclear cells from JIA synovial fluid (SF), compared to JIA and healthy control blood. Synovial monocytes and NK cells lack the Fc-receptor CD16, suggesting antibody-mediated targeting may be ineffective. B cells and DCs, both in small frequencies in SF, undergo maturation with high 4-1BB, CD71, CD39 expression, supporting T cell activation. SF effector and regulatory T cells were highly active with newly described co-receptor combinations that may alter function, and suggestion of metabolic reprogramming via CD71, TNFR2 and PD-1. Most SF effector phenotypes, as well as an identified CD4-Foxp3+ T cell population, were restricted to the inflamed joint, yet specific SF-predominant Treg (CD4+Foxp3+) subpopulations were increased in blood of active but not inactive JIA, suggesting possible recirculation and loss of immunoregulation at distal sites. This first comprehensive dataset of the site-specific inflammatory landscape at protein level will inform functional studies and the development of targeted therapeutics to restore immunoregulatory balance and achieve remission in JIA.

Graphical Abstract
Quantifying the diverse contributions of hierarchical muscle interactions to motor function
Authors: O’Reilly David , Shaw William , Hilt Pauline , de Castro Aguiar Rafael , Astill Sarah L , Delis Ioannis
Published: December 2023

The muscle synergy concept suggests that the human motor system is organised into functional modules comprised of muscles‘working together’towards common task-goals. This study offers a nuanced computational perspective to muscle synergies, where muscles interacting across multiple scales have functionally-similar, - complementary and -independent roles. Making this viewpoint implicit to a methodological approach applying Partial Information Decomposition to large-scale muscle activations, we unveiled nested networks of functionally diverse inter- and intra-muscular interactions with distinct functional consequences on task performance. This approach’s effectiveness is demonstrated using simulations and by extracting generalisable muscle networks from benchmark datasets of muscle activity. Specific network components are shown to correlate with a) balance performance and b) differences in motor variability between young and older adults. By aligning muscle synergy analysis with leading theoretical insights on movement modularity, the mechanistic insights presented here suggest the proposed methodology offers enhanced research opportunities towards health and engineering applications.
A Graph Matching Approach to Tracking Neurons in Freely-MovingC. elegans
Authors: Jones Corinne , Barzegar-Keshteli Mahsa , Gross Alice , Obozinski Guillaume , Rahi Sahand Jamal
Published: December 2023

Motivation

Recent advances in 3D microscopy allow for recording the neurons in freely-movingC. elegansat high frame rates. In order to read out calcium activity, it is necessary to track individual neurons from frame to frame. However, doing this by hand for tens of neurons in a single ten-minute recording requires more than a hundred hours. Moreover, most methods proposed in the literature for tracking neurons focus on immobilized or partially-immobilized worms and fail with freely-behaving worms.

Results

In this paper we present an approach based on graph matching for tracking fluorescently-marked neurons in freely-movingC. elegans. Neurites (and sometimes neurons) can be oversegmented into pieces at the preprocessing phase; our algorithm allows several segments to match the same reference neuron or neurite. We demon-strate our method on three recordings. We find that with five labeled frames we can typically track the neurons and pieces of neurites with over 75% accuracy, with more reliable annotations for the most distinctive neurons.

Availability and Implementation

The code and preprocessed data will be made available upon publication.

Contact

corinne.jones@epfl.ch
Evolution of hybrid inviability associated with chromosome fusions
Authors: Boman Jesper , Näsvall Karin , Vila Roger , Wiklund Christer , Backström Niclas
Published: December 2023

Chromosomal rearrangements, such as inversions, have received considerable attention in the speciation literature due to their hampering effects on recombination. However, less is known about how other rearrangements, such as chromosome fissions and fusions, can affect the evolution of reproductive isolation. Here, we used crosses between populations of the wood white butterfly (Leptidea sinapis) with different karyotypes to identify genomic regions associated with hybrid inviability. By contrasting allele frequencies between F2hybrids that survived until the adult stage with individuals of the same cohort that succumbed to hybrid incompatibilities, we show that candidate loci for hybrid inviability mainly are situated in fast-evolving regions with reduced recombination rates, especially in regions where chromosome fusions have occurred. Our results show that the extensive variation in chromosome numbers observed across the tree of life can be involved in speciation by being hotspots for the early evolution of postzygotic reproductive isolation.
The evolution of diverse antimicrobial responses in vancomycin-intermediateStaphylococcus aureusand its therapeutic implications
Authors: Crozier Dena , Gray Jason M. , Maltas Jeff A , Bonomo Robert A. , Burke Zachary D. C. , Card Kyle J , Scott Jacob G
Published: December 2023

Staphylococcus aureuscauses endocarditis, osteomyelitis, and bacteremia. Clinicians often prescribe vancomycin as an empiric therapy to account for methicillin-resistantS. aureus(MRSA) and narrow treatment based on culture susceptibility results. However, these results reflect a single time point before empiric treatment and represent a limited subset of the total bacterial population within the patient. Thus, while they may indicate that the infection is susceptible to a particular drug, this recommendation may no longer be accurate during therapy. Here, we addressed how antibiotic susceptibility changes over time by accounting for evolution. We evolved 18 methicillin-susceptibleS. aureus(MSSA) populations under increasing vancomycin concentrations until they reached intermediate resistance levels. Sequencing revealed parallel mutations that affect cell membrane stress response and cell-wall biosynthesis. The populations exhibited repeated cross-resistance to daptomycin and varied responses to meropenem, gentamicin, and nafcillin. We accounted for this variability by deriving likelihood estimates that express a population's probability of exhibiting a drug response following vancomycin treatment. Our results suggest antistaphylococcal penicillins are preferable first-line treatments for MSSA infections but also highlight the inherent uncertainty that evolution poses to effective therapies. Infections may take varied evolutionary paths; therefore, considering evolution as a probabilistic process should inform our therapeutic choices.
The implicit influence of pitch contours and emotional timbre on P300 components in an own-name oddball paradigm
Authors: Pruvost-Robieux Estelle , Joucla Coralie , Benghanem Sarah , Guha Rudradeep , Liuni Marco , Gavaret Martine , Aucouturier Jean-Julien
Published: December 2023

Objective

Previous evidence has suggested that paralinguistic features of speech stimuli may influence the characteristics of P300 components when used in clinical evaluation of consciousness. However, it remains unknown what exact acoustic components of speech are influential in such tasks, and whether they are capable of interacting with attentional deployment (as indexed by P300) in an implicit manner.

Method

To study this question, we adapted here an auditory oddball-paradigm used in clinical practice (the “own-name” paradigm), and tested whether systematic transformations of pitch contours (i.e. rising or falling intonation) and emotional timbre (i.e. smiling or rough voices) on the participants’ names influenced P300 responses in 24 healthy participants.

Results

P300 responses to rising pitch contours were smaller than to falling pitch contours, possibly reflecting an interference of the rising contours with participant attention in the deviant-counting task. No such difference was observed with emotional timbre variations.

Conclusion and Significance

These results suggest that the cognitive resources involved in pitch contour processing overlap more strongly than timbre with the resources required to count own-name deviants, and that rising pitch contours should be tested prospectively as a way to increase the saliency of consciousness evaluation in unconscious patients.
Multi-task machine learning reveals the neuroanatomy fingerprint of mental processing
Authors: Wang Zifan , Chen Yuzhong , Mao Wei , Xiao Zhenxiang , Cao Guannan , Toussaint Paule-J , Guo Weitong , Zhao Boyu , Sun Hailin , Zhang Tuo , Evans Alan C , Jiang Xi
Published: December 2023

Mental processing delineates the functions of the human mind encompassing a wide range of motor, sensory, emotional, and cognitive processes, each of which is underlain by the neuroanatomical substrates. Identifying accurate representation of neuroanatomical substrates of mental processing could inform understanding of its neural mechanism. The challenge is that it is unclear whether a specific mental process possesses a ’neuroanatomy fingerprint’, i.e., a unique pattern of neuroanatomy that determines the mental process. We used multi-task deep learning to disentangle the neuroanatomy fingerprint of a mental process from other multiple mental processes. The neuroanatomy fingerprint is a unique set of functional activity strength of whole-brain regions with high discrimination ability (AUC = 0.99) among different mental processes. The functional activity strength distribution of neuroanatomy fingerprint unveils both common and distinct brain regions involved in different mental processes. The neuroanatomy fingerprint also addresses a long-standing hypothesis: At least in Chinese and US populations, there consistently exists a neuroanatomy fingerprint to underlie the associated mental process.

One-Sentence Summary

Each mental process has a neuroanatomy fingerprint, which is represented as a unique pattern of functional activity strength of whole-brain regions, to differentiate from other different mental processes.