bluuebunny/crossref_metadata_2025 huggingface dataset:
Compulsory treatment at home: an interview study exploring the experiences of an early group of patients, relatives and mental-health workers
Authors: de Waardt D. A. , de Jong I. C. , Lubben M. , Haakma I. , Mulder C. L. , Widdershoven G. A. M.
Published: November 2024

Background

When introduced in 2020, the Netherlands’ Compulsory Mental Healthcare Act included provisions for compulsory community treatment (CCT) and compulsory treatment in patients’ homes (CTH). Although CCT has been incorporated into mental health care in many countries, its effectiveness is debated. We know of no other countries in which CTH has been adopted.

The aim of this study is to evaluate how an early group of participants experienced CTH. They were drawn from three stakeholder groups: patients, relatives and mental-health workers.

Methods

In total, 17 open interviews were conducted with six patients, five relatives and six mental-health workers. All had experience with CTH. Thematic analysis was used to analyze the interviews.

Results

Five themes were identified: 1). Reasons for applying for a court order with options for CTH. The reasons included preventing harm, avoiding hospitalization, and providing a safety net. 2.) Participants’ experiences with CTH in practice. The four most noteworthy experiences were related to the process of applying for a court order; compulsory home visits and the compulsory use of medication; the involvement of relatives during treatment; and the influence of CTH on the relationship between patients and relatives.  3.) The advantages and disadvantages of CTH. The most important advantages were avoiding hospitalization; improving medication adherence; facilitating easy access to care; early signaling of deterioration; early intervention; and regained autonomy. The most important disadvantages were restricted autonomy; fewer options for monitoring compared to hospitalization; and problems regarding control of patient behavior. 4.) Participants’ preferences. All preferred CTH to hospitalization. 5.) Participants’ suggestions for improving CTH. These included the need not only to provide patients with better information, but also to improve the involvement of relatives during treatment.

Conclusion

The interviewees found that CTH might help to avoid hospitalization by providing stakeholders with more options for arranging effective care at home. Although this suggests that initial experiences of CTH under the new Dutch mental health law were positive, it is still uncertain whether CTH as currently implemented really differs from CCT.
Role of glucagon-like peptide-1 receptor agonists in Alzheimer’s disease and Parkinson’s disease
Authors: Hong Chien-Tai , Chen Jia-Hung , Hu Chaur-Jong
Published: November 2024

Neurodegenerative diseases, including Alzheimer’s Disease (AD) and Parkinson’s Disease (PD) are common complications of diabetes, arising from insulin resistance, inflammation, and other pathological processes in the central nervous system. The potential of numerous antidiabetic agents to modify neurodegenerative disease progression, both preclinically and clinically, has been assessed. These agents may provide additional therapeutic benefits beyond glycemic control. Introduced in the twenty-first century, glucagon-like peptide-1 receptor agonists (GLP-1RAs) are a class of antidiabetic drugs noted not only for their potent glucose-lowering effects but also for their cardiovascular and renal protective benefits. Various GLP-1RAs have been demonstrated to have significant benefits in in vitro and in vivo models of neurodegenerative diseases through modulating a variety of pathogenic mechanisms, including neuroinflammation, autophagy, mitochondrial dysfunction, and the abnormal phosphorylation of pathognomonic proteins. These agents also have substantial protective effects on cognitive and behavioral functions, such as motor function. However, clinical trials investigating GLP-1RAs in diseases such as AD, PD, mild cognitive impairment, psychiatric disorders, and diabetes have yielded mixed results for cognitive and motor function. This review examines the link between diabetes and neurodegenerative diseases, explores the effects of antidiabetic agents on neurodegeneration, provides a concise overview of the GLP-1 pathway, and discusses both preclinical and clinical trial outcomes of GLP-1RAs for neurodegenerative diseases, including their effects on cognition in AD and PD. This review also proposed new strategies for the design of future clinical trials on GLP-1 RAs for both AD and PD.
Role of joint interactions in upper limb joint movements: a disability simulation study using wearable inertial sensors for 3D motion capture
Authors: Bhagat Nishtha , Raghavan Preeti , Kapila Vikram
Published: November 2024

Background

Restriction of movement at a joint due to disease or dysfunction can alter the range of motion (ROM) at other joints due to joint interactions. In this paper, we quantify the extent to which joint restrictions impact upper limb joint movements by conducting a disability simulation study that used wearable inertial sensors for three-dimensional (3D) motion capture.

Methods

We employed the Wearable Inertial Sensors for Exergames (WISE) system for assessing the ROM at the shoulder (flexion–extension, abduction–adduction, and internal–external rotation), elbow (flexion–extension), and forearm (pronation-supination). We recruited 20 healthy individuals to first perform instructed shoulder, elbow, and forearm movements without any external restrictions, and then perform the same movements with restriction braces placed to limit movement at the shoulder, elbow, and forearm, separately, to simulate disability. To quantify the extent to which a restriction at a non-instructed joint affected movement at an instructed joint, we computed average percentage reduction in ROM in the restrictedversusunrestricted conditions. Moreover, we performed analysis of variance and post hoc Tukey tests (qstatistic) to determine the statistical significance (p < 0.05 denoted using *) of the differences in ROM of an instructed joint in the unrestrictedversusrestricted conditions.

Results

Restricting movement at the shoulder led to a large reduction in the average ROM for elbow flexion–extension (21.93%,q = 9.34*) and restricting elbow movement significantly reduced the average ROM for shoulder flexion–extension (17.77%,q = 8.05*), shoulder abduction–adduction (19.80%,q = 7.60*), and forearm pronation-supination (14.04%,q = 4.96*). Finally, restricting the forearm significantly reduced the average ROM for shoulder internal–external rotation (16.71%,q = 3.81*) and elbow flexion–extension (10.01%,q = 4.27*).

Conclusions

Joint interactions across non-instructed joints can reduce the ROM of instructed movements. Assessment of ROM in the real-world using 3D motion capture, for example using the WISE system, can aid in understanding movement limitations, informing interventions, and monitoring progress with rehabilitation.
Ren-Shen-Bu-Qi decoction alleviates exercise fatigue through activating PI3K/AKT/Nrf2 pathway in mice
Authors: Chen Yangyang , Gao Tinghui , Bai Jing , Zhang Wenjing , Zhou Yutong , Zhao Ruichang , Deng Youhui , Liu Xiaogang , Huang Zhangjun , Wang Songtao , Shen Caihong , Liu Sijing , Guo Jinlin
Published: November 2024

Background

Fatigue is a prevalent issue that can lead individuals to a sub-health condition, impacting their work efficiency and quality of life. There are limited effective treatment options available for fatigue. Ren-Shen-Bu-Qi decoction (RSBQD) is a proprietary herbal remedy that is designed to address fatigue. However, the specific pharmacological mechanisms and basis of RSBQD are not yet fully understood.

Purpose

This study aimed to investigate the pharmacological effects and mechanisms of RSBQD in a mouse model of exercise fatigue.

Materials and methods

UPLC-Q-Orbitrap HRMS was used to analyze the chemical composition of RSBQD. The pharmacological basis and molecular mechanism of RSBQD on exercise fatigue were predicted using network pharmacology analysis. Subsequently, an exercise fatigue mouse model was established and used to analysis the effects of RSBQD. The potential mechanisms were verified by hematoxylin–eosin (HE) staining, real-time fluorescence quantitative PCR (RT-qPCR), Western blot (WB) and molecular docking.

Results

The results showed that 88 main components of RSBQD were identified, which have mainly belonged to flavonoids and carboxylic acid compounds. The network pharmacology analysis indicated that RSBQD ameliorate fatigue through PI3K/AKT signaling pathway. Notably, RSBQD prolonged the swimming time and diminished body weight loss of exercise fatigue mice (P < 0.05). Meanwhile, RSBQD significantly alleviated the injury of liver and kidney induced by exhaustive exercise, and decreasing the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea and BUN levels (P < 0.05). In addition, RSBQD was found could relieve exercise fatigue by decreasing the content of creatine kinase (CK), lactate dehydrogenase (LDH), and lactic acid (LA), but increasing the blood glucose (GLU) and liver glycogen (HG) levels (P < 0.05). RSBQD also significantly increased the hepatic superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) but decreased hepatic malondialdehyde (MDA) levels. Moreover, RSBQD was able to upregulate protein level of activated Nrf2 and PI3K/AKT signaling pathways.

Conclusions

RSBQD mitigates exercise fatigue by reversing metabolic changes and reducing oxidative damage through the PI3K/AKT/Nrf2 signaling pathway. This study offers pharmacological support for the utilization of RSBQD in exercise fatigue treatment.

Graphical Abstract
Quality of life and mental health status in caregivers of pediatric patients with nephropathic cystinosis
Authors: González Karina , Eixarch Teresa , Nuñez Laura , Ariceta Gema
Published: November 2024

There are few studies assessing psychological burden and quality of life (QoL) in caregivers of pediatric patients with nephropathic cystinosis, a severe chronic disease. This observational, single-center study aimed to explore the levels of anxiety, depression, care burden, and QoL status in caregivers of patients with nephropathic cystinosis. The Hospital Anxiety and Depression Scale (HADS), the Zarit Caregiver Burden Scale, and the Short Form-36 (SF-36) were administered to caregivers of pediatric patients with nephropathic cystinosis. Nine caregivers of pediatric patients with nephropathic cystinosis participated in the study (6 boys and 3 girls; mean age, 12.6 ± 4.2 years). All participating caregivers were the patient’s mothers. Of the 9 caregivers, 6 showed anxiety/depression and 4 severe care burden. Overall, SF-36 QoL domains with a worse perception by caregivers were ‘general health’ and ‘health change over time’. Mothers without depression/anxiety and low care burden had better QoL perception (p = 0.02). All caregivers with high care burden showed anxiety/depression. In our study cohort, caregivers of pediatric patients with nephropathic cystinosis showed high levels of anxiety/depression, high care burden, and impaired QoL, highlighting the importance of detecting psycho-social issues to implement strategies that relieve family stress and improve coping strategies.
Study on the disease burden of patients with mucopolysaccharidosis type II in China
Authors: Yuan Ni , Li Min , Wang Shan-Shan , Yu Hua-Xin , Wang Ya-Qun , Dong Fan-Yu , Chen Han-Xiang , Duan Sheng-Nan , Luo Ji
Published: November 2024

Background

In this study, we investigated the patient population of Mucopolysaccharidosis type II (MPS II) in China, understood the basic situation, prevalence and diagnosis and treatment status of the patients, as well as the economic burden of the patients, and analyzed the influencing factors.

Methods

A cross-sectional study focusing on patients with MPS II was conducted in China in 2023. Participants in the study were drawn from the Beijing Zhengyu Mucopolysaccharide Rare Disease Care Center, which is the only non-profit organization in mainland China registered with the civil affairs department that focuses on mucopolysaccharidosis. Data were collected through an online questionnaire, which included basic patient information, disease status, self-assessment of quality of life, diagnosis and treatment, as well as direct and indirect medical costs. The demographic and diagnosis and treatment profile of patients were analyzed by descriptive statistics. Furthermore, univariate and multiple linear regression were used to explore the economic burden and influencing factors of patients with MPS II.

Results

The survival data of 145 patients were collected, the majority (98.62%) were male, and 78 were less than or equal to 10 years old. All patients were covered by medical insurance, mainly urban residents (135 cases). In terms of expenses, the 124 patients in the year before the survey incurred a total cost of about 14.7895 million yuan, and the direct economic burden accounted for 87.19%. Univariate analysis showed that age, number of hospitalizations, length of hospital stay, number of outpatient/emergency departments, hematopoietic stem cell transplantation (HSCT), and enzyme replacement therapy (ERT) were significantly associated with the economic burden of disease. Multiple regression analysis showed that the number of hospitalizations, days of hospitalization, number of outpatient/emergency departments and HSCT treatment were the main influencing factors.

Conclusions

This study found that patients with MPS II were difficult to diagnose and easily misdiagnosed, their physical functions were impaired in many aspects. The existing treatment options are not sufficient in terms of economy and effectiveness, and there is also a lack of corresponding policy guarantees and support, which makes patients and their families have to face huge financial pressure.
A nanoencapsulated oral formulation of fenretinide promotes local and metastatic breast cancer dormancy in HER2/neu transgenic mice
Authors: De Angelis Maria Laura , Francescangeli Federica , Aricò Eleonora , Verachi Paola , Zucchetti Massimo , Matteo Cristina , Petricci Elena , Pilozzi Emanuela , Orienti Isabella , Boe Alessandra , Eramo Adriana , Rossi Rachele , Corati Tiberio , Macchia Daniele , Pacca Anna Maria , Zeuner Ann , Baiocchi Marta
Published: November 2024

Background

Prevention and treatment of metastatic breast cancer (BC) is an unmet clinical need. The retinoic acid derivative fenretinide (FeR) was previously evaluated in Phase I-III clinical trials but, despite its excellent tolerability and antitumor activity in preclinical models, showed limited therapeutic efficacy due to poor bioavailability. We recently generated a new micellar formulation of FeR, Bionanofenretinide (Bio-nFeR) showing enhanced bioavailability, low toxicity, and strong antitumor efficacy on human lung cancer, colorectal cancer, and melanoma xenografts. In the present study, we tested the effect of Bio-nFeR on a preclinical model of metastatic BC.

Methods

We used BC cell lines for in vitro analyses of cell viability, cell cycle and migratory capacity. For in vivo studies, we used HER2/neu transgenic mice (neuT) as a model of spontaneously metastatic BC. Mice were treated orally with Bio-nFeR and at sacrifice primary and metastatic breast tumors were analyzed by histology and immunohistochemistry. Molecular pathways activated in primary tumors were analyzed by immunoblotting. Stem cell content was assessed by flow cytometry, immunoblotting and functional assays such as colony formation ex vivo and second transplantation assay in immunocompromised mice.

Results

Bio-nFeR inhibited the proliferation and migration of neuT BC cells in vitro and showed significant efficacy against BC onset in neuT mice. Importantly, Bio-nFeR showed the highest effectiveness against metastatic progression, counteracting both metastasis initiation and expansion. The main mechanism of Bio-nFeR action consists of promoting tumor dormancy through a combined induction of antiproliferative signals and inhibition of the mTOR pathway.

Conclusion

The high effectiveness of Bio-nFeR in the neuT model of mammary carcinogenesis, coupled with its low toxicity, indicates this formulation as a potential candidate for the treatment of metastatic BC and for the adjuvant therapy of BC patients at high risk of developing metastasis.
Interplay of paternal caregiving and screen use habits on early childhood development and children’s tantrums
Authors: Sari Emre , Yalçın Sıddıka Songül
Published: November 2024

Background

This study aims to examine the association for paternal care and father-child screen use with early childhood development and children’s temper tantrums.

Method

Study file included questions about paternal characteristics, child care, father-child screen habits, and utilized the UNICEF Early Childhood Development Index (ECDI). Factors influencing ECDI-on-track status and children’s responses when screen use was restricted were investigated with Chi-square test and multiple logistic regression.

Results

The study included 464 fathers having children aged 3–4 years. The findings showed that 89.7% of the children were on track in three out of the four ECDI subgroups. When screen use was restricted, 55.6% of the children engaged in another activity, while 44.4% reacted by crying. Multiple logistic regression analysis revealed that the father’s education level, the child’s age and gender, the starting age for screen usage, the child’s reaction to screen restriction, and having three or more books were associated with ECDI. Furthermore, the child’s reaction to screen restriction was related to the child’s and father’s screen time, the presence of three or more books, the adequacy of care, and being on track in the literacy-numeracy ECDI subgroup.

Conclusion

Screen usage habits significantly impact early childhood development and children’s reactions to screen restrictions. These findings underscore the importance of educating fathers about the effects of their own and their child’s media habits, the quality of fatherly caregiving, and the presence of books in fostering positive child development.
CaClust: linking genotype to transcriptional heterogeneity of follicular lymphoma using BCR and exomic variants
Authors: Oksza-Orzechowski Kazimierz , Quinten Edwin , Shafighi Shadi , Kiełbasa Szymon M. , van Kessel Hugo W. , de Groen Ruben A. L. , Vermaat Joost S. P. , Sepúlveda Yáñez Julieta H. , Navarrete Marcelo A. , Veelken Hendrik , van Bergen Cornelis A. M. , Szczurek Ewa
Published: November 2024

Tumours exhibit high genotypic and transcriptional heterogeneity. Both affect cancer progression and treatment, but have been predominantly studied separately in follicular lymphoma. To comprehensively investigate the evolution and genotype-to-phenotype maps in follicular lymphoma, we introduce CaClust, a probabilistic graphical model integrating deep whole exome, single-cell RNA and B-cell receptor sequencing data to infer clone genotypes, cell-to-clone mapping, and single-cell genotyping. CaClust outperforms a state-of-the-art model on simulated and patient data. In-depth analyses of single cells from four samples showcase effects of driver mutations, follicular lymphoma evolution, possible therapeutic targets, and single-cell genotyping that agrees with an independent targeted resequencing experiment.
Interleukin-6 receptor antibodies (tocilizumab) in acute myocardial infarction with intermediate to high risk of cardiogenic shock development (DOBERMANN-T): study protocol for a double-blinded, placebo-controlled, single-center, randomized clinical trial
Authors: Kunkel Joakim Bo , Holle Sarah Louise Duus , Hassager Christian , Pecini Redi , Wiberg Sebastian , Palm Pernille , Holmvang Lene , Bang Lia Evi , Kjærgaard Jesper , Thomsen Jakob Hartvig , Engstrøm Thomas , Møller Jacob Eifer , Lønborg Jacob Thomsen , Frydland Martin , Søholm Helle
Published: November 2024

Background

Inflammation and neurohormonal activation play a significant role in the adverse outcome seen in acute myocardial infarction (AMI) and the development of cardiogenic shock (CS), which is associated with a mortality rate up to 50%. Treatment with anti-inflammatory drugs such as tocilizumab, an interleukin-6 receptor antagonist, has been shown to reduce troponin release and reduce the myocardial infarct size in AMI patients and it may therefore have cardioprotective properties.

Methods

This is a double-blind, placebo-controlled, single-center randomized clinical trial, including adult AMI patients without CS at hospital arrival, undergoing percutaneous coronary intervention (PCI) within 24 h from symptom onset, and at intermediate to high risk of developing CS (ORBI risk score ≥ 10). A total of 100 participants will be randomized to receive a single intravenous dose of tocilizumab (280 mg) or placebo (normal saline). The primary outcome is peak plasma pro-B-type natriuretic peptide (proBNP) within 48 h, assessed using serial measurements at intervals: before infusion, 12, 24, 36, and 48 h after infusion. Secondary endpoints include the following: (1) cardiac magnetic resonance imaging (CMR) during 24–48 h after admission and at follow-up after 3 months with assessment of left ventricular area at risk, final infarct size, and the derived salvage index and (2) biochemical markers of inflammation (C-reactive protein and leukocyte counts) and cardiac injury (troponin T and creatinine kinase MB).

Discussion

Modulation of interleukin-6-mediated inflammation in patients with AMI, treated with acute PCI, and at intermediate to high risk of in-hospital CS may lead to increased hemodynamic stability and reduced left ventricular infarct size, which will be assessed using blood biomarkers with proBNP as the primary outcome and inflammatory markers, troponin T, and CMR with myocardial salvage index as the secondary endpoints.

Trial registration

Registered with the Regional Ethics Committee (H-21045751), EudraCT (2021–002028-19), ClinicalTrials.gov (NCT05350592). Study registration date: 2022-03-08, Universal Trial Number U1111-1277–8523.
Associations between biomarkers and skeletal muscle function in individuals with osteoarthritis: a systematic review and meta-analysis
Authors: Smith Stephanie L. , Paul Lorna , Steultjens Martijn P. M. , Jones Rebecca L.
Published: November 2024

Objectives

Skeletal muscle dysfunction is the primary cause of functional limitations in osteoarthritis, associated biomarkers have the potential as targets for early disease identification, diagnosis, and prevention of osteoarthritis disability. This review aimed to identify associations between biomarkers and lower limb skeletal muscle function in individuals with osteoarthritis.

Methods

A systematic literature review and meta-analysis conducted in PubMed, MEDLINE, CINAHL, EMBASE, Scopus, SPORTDiscus and Web of Science databases from inception to 8th August 2023. Two independent reviewers performed the title, abstract, full-text screening, data extraction and methodological quality assessment. A meta-analysis was undertaken based on the available data.

Results

Twenty-four studies with 4101 participants with osteoarthritis were included (females: 78%; age range; 49 to 71 years). One study reported muscle-specific biomarkers (n = 3), whilst six studies reported osteoarthritis-specific markers (n = 5). Overall, 93 biomarkers were reported, predominately characterised as inflammatory (n = 35), metabolic (n = 15), and hormones (n = 10). Muscle strength and vitamin D reported a significant association (Hedge’s g: 0.58 (Standard Error (SE): 0.27; P = 0.03), k = 3 studies). Walking speed and high-sensitivity C-reactive protein reported no significant associations (Hedge’s g: -0.02 (SE: 0.05; P = 0.73), k = 3 studies).

Conclusion

Associations between biomarkers and lower limb skeletal muscle function in individuals with osteoarthritis was limited, the few studies exploring lower limb muscle measures were mainly secondary outcomes. Furthermore, biomarkers were largely related to overall health, with a lack of muscle specific biomarkers. As such, the mechanistic pathways through which these associations occur are less evident, and difficult to draw clear conclusions on these relationships.

Trial registration

Registered on PROSPERO (CRD42022359405).
Healthcare professionals’ views about delivering a rehabilitation programme for individuals living with Atrial Fibrillation: a cross – sectional survey
Authors: Alhotye Munyra , Evans Rachael , Ng Andre , Singh Sally J.
Published: November 2024

Background

People living with Atrial Fibrillation (AF) often experience symptoms such as irregular heartbeat, shortness of breath, and fatigue, which can significantly limit their physical activity and overall quality of life. The existing approach to managing AF predominantly revolves around medication and medical procedures, and no prescription of tailored rehabilitation program (RP) is currently offered for this population.

Aims

This study aims to gauge the perspectives of healthcare professionals regarding the implementation of a personalised RP for individuals living with AF and to identify the barriers hindering the referral process.

Methods

A cross-sectional online survey was conducted among healthcare professionals in the UK responsible for caring for adults with AF. The survey consisted of twelve questions designed to uncover healthcare professionals' views on RP for individuals with AF.

Results

A total of 209 respondents participated in the survey, with 57% being female and 43% identifying as specialist arrhythmia nurses. A significant majority (61%) of the participants expressed agreement that an RP could help individuals with AF regain their ability to carry out daily activities, and 58% believed that RP could effectively alleviate symptoms such as breathlessness and palpitations (52%). Virtually all respondents (99%) recommended that a tailored program should encompass education about AF, weight management, and symptom control (94%). Notably, the primary factor influencing their decision to make a referral was the low physical activity levels (80%). Transportation emerged as the chief obstacle to referring patients to the program (62%). A substantial majority (79%) favoured a home-based rehabilitation program as the optimal mean of delivery.

Conclusions

The responses from healthcare professionals reflect a keen interest in implementing a program tailored to individuals with AF, with patients' low physical activity levels being the primary motivator for referrals. Home-based rehabilitation was the preferred mode of delivery, followed by digital interventions.
An automated pheochromocytoma and paraganglioma lesion segmentation AI-model at whole-body 68Ga- DOTATATE PET/CT
Authors: Haque Fahmida , Carrasquillo Jorge A. , Turkbey Evrim B. , Mena Esther , Lindenberg Liza , Eclarinal Philip C. , Nilubol Naris , Choyke Peter L. , Floudas Charalampos S. , Lin Frank I. , Turkbey Baris , Harmon Stephanie A.
Published: November 2024

Background

Somatostatin receptor (SSR) targeting radiotracer 68Ga-DOTATATE is used for Positron Emission Tomography (PET)/Computed Tomography (CT) imaging to assess patients with Pheochromocytoma and paraganglioma (PPGL), rare types of Neuroendocrine tumor (NET) which can metastasize thereby becoming difficult to quantify. The goal of this study is to develop an artificial intelligence (AI) model for automated lesion segmentation on whole-body 3D DOTATATE-PET/CT and to automate the tumor burden calculation. 132 68Ga-DOTATATE PET/CT scans from 38 patients with metastatic and inoperable PPGL, were split into 70, and 62 scans, from 20, and 18 patients for training, and test sets, respectively. The training set was further divided into patient-stratified 5 folds for cross-validation. 3D-full resolution nnUNet configuration was trained with 5-fold cross-validation. The model’s detection performance was evaluated at both scan and lesion levels for the PPGL test set and two other clinical cohorts with NET (n = 9) and olfactory neuroblastoma (ONB, n = 5). Additionally, quantitative statistical analysis of PET parameters including SUVmax, total lesion uptake (TLU), and total tumor volume (TTV), was conducted.

Results

The nnUNet AI model achieved an average 5-fold validation dice similarity coefficient of 0.84 at the scan level. The model achieved dice similarity coefficients (DSC) of 0.88, 0.6, and 0.67 at the scan level, the sensitivity of 86%, 61.13%, and 61.64%, and a positive predictive value of 89%, 74%, and 86.54% at the lesion level for the PPGL test, NET and ONB cohorts, respectively. For PPGL cohorts, smaller lesions with low uptake were missed by the AI model (p < 0.001). Anatomical region-based failure analysis showed most of the false negative and false positive lesions within the liver for all the cohorts, mainly due to the high physiologic liver background activity and image noise on 68Ga- DOTATATE PET scans.

Conclusions

The developed deep learning-based AI model showed reliable performance for automated segmentation of metastatic PPGL lesions on whole-body 68Ga-DOTATATE-PET/CT images, which may be beneficial for tumor burden estimation for objective evaluation during therapy follow-up.

https://www.clinicaltrials.gov/study/NCT03206060, https://www.clinicaltrials.gov/study/NCT04086485, https://www.clinicaltrials.gov/study/NCT05012098.
The long non-coding RNA lncRNA-DRNR enhances infectious bronchitis virus replication by targeting chicken JMJD6 and modulating interferon-stimulated genes expression via the JAK-STAT signalling pathway
Authors: Yan Wenjun , Fu Xue , Li Hao , Wang Kailu , Song Cailiang , Hou Chengyao , Lei Cangwei , Wang Hongning , Yang Xin
Published: November 2024

Infectious bronchitis virus (IBV) is the causative agent of infectious bronchitis (IB), a severe disease that primarily affects young chickens and poses a significant challenge to the global poultry industry. Understanding the complex interaction between the virus and its host is vital for developing innovative antiviral strategies. Long non-coding RNA (lncRNA) plays a crucial role in regulating host antiviral immune responses. Our previous studies have shown that IBV infection disrupts the stability of lncRNA in host cells, indicating a potential regulatory role for lncRNA in IBV pathogenesis. It is still not clear how lncRNA precisely modulates IBV replication. In this study, we observed down-regulation ofMSTRG.26120.58 (named lncRNA-DRNR) expression in various chicken cell lines upon IBV infection. We demonstrated that silencing lncRNA-DRNR using siRNA enhances intracellular replication of IBV. Through exploring genes encoding proteins upstream and downstream of lncRNA-DRNR within a 100 kb range, we identified chJMJD6 (chicken JMJD6) as a potential target gene negatively regulated by lncRNA-DRNR expression levels. Furthermore, chJMJD6 inhibits STAT1 methylation, thereby affecting the induction of interferon-stimulated genes (ISGs) through the activation of the IFN-β-mediated JAK-STAT signalling pathway, ultimately promoting the intracellular replication of IBV. In summary, our findings reveal the critical role played by lncRNA-DRNR during IBV infection, providing novel insights into mechanisms underlying coronavirus-induced disruption in lncRNA stability.
Scaling up production of cephalosporin C by Acremonium chrysogenum W42-I in a fermenter using submerged fermentation
Authors: Ibrahim Asmaa A. , El-Housseiny Ghadir S. , Aboshanab Khaled M. , Stratmann Ansgar , Yassien Mahmoud A. , Hassouna Nadia A.
Published: November 2024

Cephalosporins presently stand as the most extensively utilized antibiotic in clinical settings. Acremonium (A.) chrysogenum is the main strain used in the manufacturing of cephalosporin C (CPC), which offers distinct advantages, including a wide-ranging antibacterial spectrum and powerful antibacterial efficacy. Our study aimed to determine the optimal conditions for scaling up the production of CPC from A. chrysogenum W42-I starting with the optimized conditions on the shake flask level obtained from our previous study and utilizing the optimized media (CPC2). The results indicated that an inoculum size equivalent to 1% v/v, aeration at 1 vvm, and an agitation rate of 400 rpm, with controlled pH at 4, were the most favorable conditions for the CPC production using a laboratory fermentor (14 L). The concentration of generated CPC was assessed using two standard curves obtained from agar well diffusion and high-performance liquid chromatography (HPLC). These optimized conditions resulted in a production of 399.52 µg/mL showing a significant increase of approximately 3.4 folds when compared to the unoptimized fermentation run. In conclusion, our findings demonstrated a more favorable time course for CPC production in the fermentor compared to that in the shake flask. Notably, there was a two-fold increase in production within the first three days. Fortunately, the fermentor achieved a noteworthy increase in output, generating 1.598 gm of the CPC within 4 L.
Motivations of Israeli physicians to return, or not, to Israel after their fellowship abroad
Authors: Seluk Lior , Weltsch Daniel , Segal Gadi , Gilboa Mayan
Published: November 2024

Background

Emigration of healthcare professionals, particularly physicians, is an unresolved “pandemic”, influenced by various factors. In high-income countries, the training phase (fellowship) abroad is critical for career development, yet it poses challenges for the retention of these professionals upon their completion of training. This study aimed to identify the determinants influencing Israeli physicians' decisions to return to their home country after completing fellowship training abroad.

Methods

This cross-sectional study conducted in early 2024, surveyed Israeli physicians with post-graduate training who pursued a fellowship abroad between 2013 and 2024. An anonymous survey included questions on demographics, training experience, and professional challenges. Analytical methods included descriptive statistics and regression analysis to explore factors associated with the decision to return.

Results

Of the 323 individuals surveyed, 297 met the inclusion criteria. Among them, 141 (47.5%) have returned to Israel, while 156 (52.5%) currently reside abroad, 48 (31%) of them have completed their fellowship. Respondents identified several challenges, beginning with a complex application process prior to fellowship (47% stated this as a major challenge), substantial financial burdens averaging 35,546 USD in direct out-of-pocket expenses during, and job uncertainty, with only 55% having secured positions upon return. Of the 156 Israeli fellows still abroad, 107 (69%) reported medium to low confidence in returning. Factors associated with a higher likelihood of confidence in returning to Israel included a secured job position upon return (OR 8.6, 95% CI 3.1–28.9) and having an opportunity for a position that would utilize the skills gained during the fellowship (OR 3.5, 95% CI 1.3–10.2).

Conclusion

The decision to return to Israel after a fellowship abroad is influenced by a mix of professional, personal, and geopolitical factors. To counteract the critical issue of brain drain, it is essential to enhance occupational certainty for returning physicians. These findings highlight the urgent need for healthcare policies that provide robust support for returning professionals and address their specific challenges.
Multi-channel neural audio decorrelation using generative adversarial networks
Authors: Anemüller Carlotta , Thiergart Oliver , Habets Emanuël A. P.
Published: November 2024

The degree of correlation between the sounds received by the ears significantly influences the spatial perception of a sound image. Audio signal decorrelation is, therefore, a commonly used tool in various spatial audio rendering applications. In this paper, we propose a multi-channel extension of a previously proposed decorrelation method based on generative adversarial networks. A separate generator network is employed for each output channel. All generator networks are optimized jointly to obtain a multi-channel output signal with the desired properties. The training objective includes a number of individual loss terms to control both the input-output and the inter-channel correlation as well as the quality of the individual output channels. The proposed approach is trained on music signals and evaluated both objectively and through formal listening tests. Thereby, a comparison with two classical signal processing-based multi-channel decorrelators is performed. Additionally, the influence of the number of output channels, the individual loss term weightings, and the employed training data on the proposed method’s performance is investigated.
Multi-scale Information Aggregation for Spoofing Detection
Authors: Li Changtao , Wan Yi , Yang Feiran , Yang Jun
Published: November 2024

Synthesis artifacts that span scales from small to large are important cues for spoofing detection. However, few spoofing detection models leverage artifacts across different scales together. In this paper, we propose a spoofing detection system built on SincNet and Deep Layer Aggregation (DLA), which leverages speech representations at different levels to distinguish synthetic speech. DLA is totally convolutional with an iterative tree-like structure. The unique topology of DLA makes possible compounding of speech features from convolution layers at different depths, and therefore the local and the global speech representations can be incorporated simultaneously. Moreover, SincNet is employed as the frontend feature extractor to circumvent manual feature extraction and selection. SincNet can learn fine-grained features directly from the input speech waveform, thus making the proposed spoofing detection system end-to-end. The proposed system outperforms the baselines when tested on ASVspoof LA and DF datasets. Notably, our single model surpasses all competing systems in ASVspoof DF competition with an equal error rate (EER) of 13.99%, which demonstrates the importance of multi-scale information aggregation for synthetic speech detection.
Non-linear connection between the triglyceride–glucose index and prediabetes risk among Chinese adults: a secondary retrospective cohort study
Authors: Cao Changchun , Han Yong , Deng Huanhua , Zhang Xiaohua , Hu Haofei , Zha Fubing , Wang Yulong
Published: November 2024

Background

The triglyceride–glucose (TyG) index has garnered recognition as a surrogate marker for insulin resistance, a pivotal factor in the pathogenesis of various metabolic disorders. Despite its emerging role, the empirical evidence delineating its association with prediabetes mellitus (Pre-DM) remains scant. This research aims to clarify the link between the TyG index and the likelihood of Pre-DM development within a Chinese demographic.

Methods

This investigation was structured as a retrospective cohort analysis, encompassing a sample of 179,177 Chinese adults. These individuals underwent medical examinations at the Rich Healthcare Group over a period spanning from 2010 to 2016. To ascertain the relationship between the TyG index and the incidence of Pre-DM, this study employed Cox regression analysis complemented by sensitivity and subgroup assessments. Furthermore, Cox proportional hazards regression with cubic spline functions and smooth curve fitting was incorporated to explore the existence of any non-linear connection within this association.

Results

Upon adjusting for a comprehensive array of confounding variables, a statistically significant positive correlation between the TyG index and the risk of Pre-DM was identified (HR: 1.60, 95%CI 1.56–1.65, P < 0.001). The analysis illuminated a non-linear relationship, with an inflection point at a TyG index value of 8.78. For TyG index values below and above this inflection point, the HR was calculated to be 1.94 (95%CI 1.86–2.03) and 1.26 (95%CI 1.20–1.33), respectively. Sensitivity analyses further fortified the reliability of these findings.

Conclusions

This comprehensive examination delineated a significantly positive, non-linear correlation between the TyG index and the risk of Pre-DM within a Chinese population. Individuals with TyG index values below 8.78 have a significantly increased risk of developing prediabetes. These findings underscore the TyG index’s potential efficacy as a predictive tool for assessing Pre-DM risk in clinical practice.
Optimized Machine Learning Algorithms for Predicting the Punching Shear Resistance of Flat Slabs with Transverse Reinforcement
Authors: Yan Hua-Jun , Xie Nan
Published: November 2024

In the calculation of reinforced concrete (RC) flat slabs with transverse reinforcement, punching shear resistance is one of the most critical factors. It is true that design provisions may be implemented, but they often result in significant biases and deviations from expectations. This study aims to present an optimized machine learning (ML) algorithm for estimating the punching shear resistance. Four machine learning (ML) algorithms (SVR, DT, RF, and XGBoost) with Bayesian optimization (BO) are presented in this paper to provide accurate predictions for flat slabs. The adoptability and optimization of the models are achieved through the analysis of a database of 337 test specimens with nine design parameters. Machine learning (ML) techniques are used to estimate punching shear resistance, which is compared with design provisions and equations relating to critical shear crack theory (CSCT). According to this study, Bayesian optimization is still capable of improving the performance of conventional machine learning algorithms, while the XGBoost-based model offers advanced capabilities. Predictions based on BO-XGBoost are in good agreement with actual values (MAE, RMSE, and R2 are 0.09 MN, 0.14 MN, and 0.92, respectively) in test set. Following a detailed explanation using Shapley additive explanation (SHAP), a high-performance ML approach is used to investigate the predictive results. With the proposed optimized algorithms, it is possible to determine the punching shear resistance of flat slabs with transverse reinforcement during the preliminary stages of the construction.
Out-of-pocket payment and catastrophic health expenditure of tuberculosis patients in accessing care at public-private mix clinics in Myanmar, 2022
Authors: Khaing Myat Noe Thiri , U Nandi , Maw Luu , Arkar Htet , Naing Saw Pa Pa , Thet May Me
Published: November 2024

Background

The financial burden of tuberculosis (TB) can hinder patients and their families, creating obstacles throughout the care cascade, despite TB prevention and control being provided free of charge. In Myanmar, patients can visit private providers operating under public-private mix (PPM) schemes, where TB services (diagnosis and treatment) are typically offered at no cost. The study focused on quantifying the financial burden faced by TB patients seeking care from Myanmar's PPM providers.

Methods

This cross-sectional telephone survey included 695 adults seeking TB treatment [drug-susceptible TB (DS-TB) and retreatment TB] from various private providers in four states and regions with high TB burden in Myanmar. Telephone interviews were conducted in May and June 2022. Both direct and indirect costs incurred from the patient and their household perspective were valued in 2022 and estimated throughout pre- and post-TB treatment episodes. The TB-affected households were defined as experiencing catastrophic health expenditure if their expenditure due to TB exceeded 20% of their capacity to pay, as recommended by the World Health Organization. All cost data were collected in Myanmar Kyats (MMK) and converted to USD (1 USD = 1850 MMK as of July 20, 2022). Logistic regression analysis was done to identify the determinants of catastrophic health expenditure.

Results

The findings showed patients made a median of 7 times for clinic visits throughout their treatment, with the median total cost for the entire TB treatment being 53.4 US dollars (USD), including direct medical and testing costs (11.9 USD) and direct non-medical patient expenditure (11.6 USD). Pre-treatment costs were higher compared to post-treatment costs (the intensive phase and continuation phase). During the intensive phase, TB care cost was nearly free, but during the continuation phase, it was a median of 2.6 USD. About 34.5% of patients experienced catastrophic health expenditure due to TB treatment, with expenses exceeding 20% of their capacity to pay. Multivariate regression analysis revealed that patients with a history of hospitalization (aOR = 14.84; P < 0.01), seeking care from regions other than Yangon (aOR = 2.6; P < 0.01), and using coping strategies (aOR = 12.53; P < 0.01), were more likely to face catastrophic financial burdens. Higher monthly household income (over 162 USD) was associated with a decreased risk of incurring catastrophic health expenditure (aOR = 0.38; P < 0.01).

Conclusions

TB patients and their households in Myanmar faced risk of catastrophic costs, even when treated in the private sector with free diagnostic charges and anti-TB medicine. The study highlighted the need for additional strategies or policies to make TB care affordable and mitigate the financial burden of TB-affected households.

Graphical Abstract
Clinical characteristics and short-term outcomes of patients with critical acute pulmonary embolism requiring extracorporeal membrane oxygenation: from the COMMAND VTE Registry-2
Authors: Takabayashi Kensuke , Yamashita Yugo , Morimoto Takeshi , Chatani Ryuki , Kaneda Kazuhisa , Nishimoto Yuji , Ikeda Nobutaka , Kobayashi Yohei , Ikeda Satoshi , Kim Kitae , Inoko Moriaki , Takase Toru , Tsuji Shuhei , Oi Maki , Takada Takuma , Otsui Kazunori , Sakamoto Jiro , Ogihara Yoshito , Inoue Takeshi , Usami Shunsuke , Chen Po-Min , Togi Kiyonori , Koitabashi Norimichi , Hiramori Seiichi , Doi Kosuke , Mabuchi Hiroshi , Tsuyuki Yoshiaki , Murata Koichiro , Nakai Hisato , Sueta Daisuke , Shioyama Wataru , Dohke Tomohiro , Nishikawa Ryusuke , Ono Koh , Kimura Takeshi ,   On behalf of the COMMAND VTE Registry-2 Investigators
Published: November 2024

Background

Extracorporeal membrane oxygenation (ECMO) might be required as a treatment option in patients with critical pulmonary embolism (PE). However, the clinical features and outcomes of the use of ECMO for critical acute PE are still limited. The present study aimed to clarify the clinical characteristics, management strategies and outcomes of patients with acute PE requiring ECMO in the current era using data from a large-scale observational database.

Methods

We analyzed the data of the COMMAND VTE Registry-2: a physician-initiated, multicenter, retrospective cohort study enrolling consecutive patients with acute symptomatic venous thromboembolism (VTE). Among 2035 patients with acute symptomatic PE, there were 76 patients (3.7%) requiring ECMO.

Results

Overall, the mean age was 58.4 years, and 34 patients (44.7%) were men. Cardiac arrest or circulatory collapse at diagnosis was reported in 67 patients (88.2%). The 30-day incidence of all-cause death was 30.3%, which were all PE-related deaths. The 30-day incidence of major bleeding was 54.0%, and the vast majority of bleedings were procedure site-related bleeding events and surgery-related bleeding (22.4%). The 30-day incidence of all-cause death was 6.3% in 16 patients with surgical intervention, 43.8% in 16 patients with catheter intervention, 25.0% in 16 patients with thrombolytic therapy, and 39.3% in 28 patients with anticoagulation only.

Conclusions

The current large real-world VTE registry in Japan revealed clinical features and outcomes of critical acute PE requiring ECMO in the current era, which suggested several unmet needs for future clinical trials.