bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multimodal deep learning model to infer cell-type-specific functional gene networks
Authors: Afshar Shiva , Braun Patricia R. , Han Shizhong , Lin Ying 
Published: February 2023

Abstract
Background
Functional gene networks (FGNs) capture functional relationships among genes that vary across tissues and cell types. Construction of cell-type-specific FGNs enables the understanding of cell-type-specific functional gene relationships and insights into genetic mechanisms of human diseases in disease-relevant cell types. However, most existing FGNs were developed without consideration of specific cell types within tissues.

Results
In this study, we created a multimodal deep learning model (MDLCN) to predict cell-type-specific FGNs in the human brain by integrating single-nuclei gene expression data with global protein interaction networks. We systematically evaluated the prediction performance of the MDLCN and showed its superior performance compared to two baseline models (boosting tree and convolutional neural network). Based on the predicted cell-type-specific FGNs, we observed that cell-type marker genes had a higher level of hubness than non-marker genes in their corresponding cell type. Furthermore, we showed that risk genes underlying autism and Alzheimer’s disease were more strongly connected in disease-relevant cell types, supporting the cellular context of predicted cell-type-specific FGNs.

Conclusions
Our study proposes a powerful deep learning approach (MDLCN) to predict FGNs underlying a diverse set of cell types in human brain. The MDLCN model enhances prediction accuracy of cell-type-specific FGNs compared to single modality convolutional neural network (CNN) and boosting tree models, as shown by higher areas under both receiver operating characteristic (ROC) and precision-recall curves for different levels of independent test datasets. The predicted FGNs also show evidence for the cellular context and distinct topological features (i.e. higher hubness and topological score) of cell-type marker genes. Moreover, we observed stronger modularity among disease-associated risk genes in FGNs of disease-relevant cell types. For example, the strength of connectivity among autism risk genes was stronger in neurons, but risk genes underlying Alzheimer’s disease were more connected in microglia.
The effect of combining therapeutic drug monitoring of antihypertensive drugs with personalised feedback on adherence and resistant hypertension: the (RHYME-RCT) trial protocol of a multi-centre randomised controlled trial
Authors: Peeters L. E. J. , Kappers M. H. W. , Boersma E. , Massey E. K. , van Dijk L. , van Gelder T. , Koch B. C. P. , Versmissen J. 
Published: February 2023

AbstractBackgroundAdherence to antihypertensive drugs (AHDs) is important for adequate blood pressure control. Not taking these drugs as prescribed is one of the main underlying causes for resistant hypertension (RH), which in turn leads to an increased risk of cardiovascular events, stroke and kidney damage. Therefore, correct identification of patients that are non-adherent to AHDs is crucial to improve clinical outcome. For this goal, therapeutic drug monitoring is the most reliable method. The primary objective of this trial is to investigate whether monitoring of drug concentrations with a dried blood spot (DBS) sampling method combined with personalised feedback leads to a decrease in prevalence of RH after 12 months due to an increase in adherence. Secondary objectives include the difference over time in the number of required AHDs as well as the defined daily dose (DDD). Lastly, the cost-utility of SoC versus the intervention in RH is determined.MethodsThis is a multi-centre single-blinded randomised controlled trial (RHYME-RCT). First, at an eligibility visit, DBS sampling, to monitor drug concentrations in blood, and a 24-h ambulatory blood pressure measurement (24-h ABPM) are performed simultaneously. Patients with a daytime systolic blood pressure (SBP) > 135 and/or diastolic blood pressure (DBP) > 85 mmHg are randomised to SoC or intervention + SoC. The intervention is performed by the treating physician and includes information on drug concentrations and a comprehensive personalised feedback conversation with the use of a communication tool. The follow-up period is one year with visits at 3, 6 and 12 months randomisation and includes 24-h ABPM and DBS sampling.DiscussionThis will be the first trial that focusses specifically on patients with RH without taking into account suspicion of non-adherence and it combines monitoring of AHD concentrations to identify non-adherence to AHDs with a comprehensive feedback to improve non-adherence. Furthermore, if this trial shows positive outcomes for the intervention it can be directly implemented in clinical practice, which would be a great improvement in the treatment of RH.Trial registration. RHYME-RCT is registered in the Dutch Trial Register on 27/12/2017 (NTR6914) and can be found in the International Clinical Trials Registry Platform.
The effects of high versus low frequency of combined physical and cognitive training on cognitive function in older adults with cognitive decline: a quasi-experimental study
Authors: Chuang I-Ching , Chen I-Chen , Su Ken-Hsien , Wu Yih-Ru , Wu Ching-Yi 
Published: February 2023

Abstract
Background
The effects of combined training can be affected by training characteristics such as frequency, session length, and duration. No empirical studies to date have directly compared how combined physical and cognitive training offered at different training frequencies affects cognitive function for older adults with cognitive decline. This study investigated the impact of training frequency on cognitive outcomes after combined physical and cognitive training for older adults with cognitive decline.

Methods
A quasi-experimental study was conducted in community facilities and day care centers. The study assigned 89 older adults with cognitive decline into high-frequency (HF) or low-frequency (LF) training groups. The participants received 90- to 105-min training sessions, one (LF) or three (HF) times a week, for 12 weeks. Outcome measures were the Montreal Cognitive Assessment, Word List subtest of the Wechsler Memory Scale, Digit Symbol Substitution Test (DSST), and Stroop Color Word Test.

Results
The HF group demonstrated greater improvement in immediate memory measured by the WL-IM (F = 8.7, P = 0.004) and in executive function measured by the SCWT (F = 5.89, P = 0.017) than the LF group. Compared with the HF group, the LF group showed a great improvement in delayed memory measured by the WL-DM (F = 9.62, P = 0.003). The HF and LF groups both increased in processing speed and global cognitive function.

Conclusions
Our study indicated that the different training frequency of combined physical and cognitive training may result in benefits on different cognitive functions in older adults with cognitive decline. These findings may assist clinical practitioners in choosing appropriate training frequencies based on various intervention purposes for the elderly with cognitive decline.

Trial registration
ClinicalTrials.gov Identifier NCT03619577 (08/08/2018).
Biomarkers of macular neovascularisation activity using optical coherence tomography angiography in treated stable neovascular age related macular degeneration
Authors: Hanumunthadu Daren , Saleh Azahir , Florea Daniela , Balaskas Konstantinos , Keane Pearse A , Aslam Tariq , Patel Praveen J. 
Published: February 2023

Abstract
Background
The aim of this study was to describe features of disease activity in patients with treated stable macular neovascularisation (MNV) in neovascular age related macular degeneration (nAMD) using optical coherence tomography angiography (OCTA).

Methods
Thirty-two eyes of 32 patients with nAMD were included in this prospective, observational study. These patients were undergoing treatment with aflibercept on a treat-and-extend regimen attending an extension to a 12-week treatment interval.

Results
All subjects had no macular haemorrhage and no structural OCT markers of active MNV activity at the index 12-week treatment extension visit. 31/32 OCTA images were gradeable without significant imaging artefact. The mean MNV size was 3.6mm2 ± 4.6mm2 and 27 (87.1%) had detectable MNV blood flow. 29/31 (93.5%) subjects had MNV with mature phenotypes including 10 non-specific, 10 tangle and 3 deadtree phenotypes. MNV halo and MNV central feeder vessel were noted in 18 (58.1%) and 19 (61.3%) of subjects respectively; only 1 (3.2%) subject was noted to have a MNV capillary fringe.

Conclusions
MNV blood flow is still detectable using OCTA in the majority of subjects in this study with treated stable MNV. OCTA features associated included MNV mature phenotype, MNV feeder vessel, MNV halo and absence of capillary fringe.
Diagnostic pathways of Chagas disease in Spain: a qualitative study
Authors: Iglesias-Rus Laura , Boquete Teresa , Romay-Barja María , Benito Agustín , Jordan Briggitte , Blasco-Hernández Teresa 
Published: February 2023

Abstract
Background
Due to the mobility of the population in recent years and the spread of Chagas disease (CD) to non-endemic regions, early diagnosis and treatment of CD has become increasingly relevant in non-endemic countries. In order for screening to be effective, health system accessibility must be taken into consideration. This study uses Tanahashi’s Health Service Coverage model to gain a deeper understanding of the main diagnostic pathways for Chagas disease in a non-endemic country and the barriers and bottlenecks present in each pathway.

Methods
This study used a qualitative design with a phenomenological approach. Twenty-one interviews, two focus group sessions, and two triangular group sessions were conducted between 2015 and 2018 with 37 Bolivian men and women diagnosed with CD in Madrid, Spain. A topic guide was designed to ensure that the interviewers obtained the data concerning knowledge of CD (transmission, symptoms, and treatment), attitudes towards CD, and health behaviour (practices in relation to CD). All interviews, focus groups and triangular groups were recorded and transcribed. A thematic, inductive analysis based on Grounded Theory was performed by two researchers.

Results
Three main pathways to CD diagnosis were identified: 1) pregnancy or blood/organ donation, with no bottlenecks in effective coverage; 2) an individual actively seeking CD testing, with bottlenecks relating to administrative, physical, and time-related accessibility, and effectiveness based on the healthcare professional’s knowledge of CD; 3) an individual not actively seeking CD testing, who expresses psychological discomfort or embarrassment about visiting a physician, with a low perception of risk, afraid of stigma, and testing positive, and with little confidence in physicians’ knowledge of CD.

Conclusions
Existing bottlenecks in the three main diagnostic pathways for CD are less prevalent during pregnancy and blood donation, but are more prevalent in individuals who do not voluntarily seek serological testing for CD. Future screening protocols will need to take these bottlenecks into consideration to achieve effective coverage.
De novo HNF1A mutation of young maturity-onset diabetes 3 of a young girl—Case report
Authors: Peng Haoran , Li Jianbo , Wang Zhang 
Published: February 2023

AbstractYoung maturity-onset diabetes of the young type3(MODY3) as a special type of diabetes, the probability of diagnosis is low. This article reports on a case and reviews the relevant knowledge of the disease. We report an 11-year-and-11-month-old girl whose grandmother died from diabetic complications while the rest of the families were non-diabetes. The proband was initially treated with insulin and metformin but the threatment proved inefficient. After an exome-targeted capture sequencing test, she was diagnosed with mature-onset diabetes of young type 3 (MODY3), and sulfonylureas make sense. The key to mody treatment is a correct and timely diagnosis, which contributes to helping patients overcome the problems of MODY3, especially for blood sugar control.
Development and psychometric evaluation of a self-management behaviours scale in rheumatoid arthritis patients (RA-SMBS)
Authors: Chen Jinglin , Song Yuqing , Ou Lihong , Wang Xia , Wang Ying , Chen Yanling , Chen Hong 
Published: February 2023

Abstract
Background
Self-management behaviours can be crucial to improving disease symptoms and health outcomes in rheumatoid arthritis (RA) patients. Currently, the tools available for measuring self-management behaviours in RA patients are either generalized for patients with chronic diseases, which lack specificity or have poor reliability in the only specific scale—self-care behaviours scale (SCBS). The aim of this study was to develop a self-management behaviours scale for RA patients and evaluate its psychometric properties.

Methods
The study included two steps: scale development and the psychometric evaluation. The items were developed from a literature review, in-depth individual interviews, nominal group technique, Delphi expert consultation, and a pilot test. For the psychometric evaluation, a sample of 561 patients with RA was recruited. Item analysis, content validity, exploratory and confirmatory factor analysis, convergent and discriminant validity, and internal consistency reliability were conducted to examine the psychometric properties of the RA-SMBS.

Results
The final scale consists of 23 items with 4 dimensions, including medication management, exercise and joint protection, resource utilization and emotional management, and symptom management. The content validity index was 0.78. Exploratory factor analysis explained 61.89% of the total item variance. Confirmatory factor analysis indicated that the RA-SMBS fit well. Good internal consistency reliability was demonstrated (Cronbach's alpha = 0.908), and the test–retest reliability was found to be acceptable (ICC = 0.628, r = 0.780).

Conclusions
The scale has good content validity, construct validity, and internal consistency reliability. It can be used to assess the level of self-management behaviours in RA patients.
Quantification of parasite clearance in Plasmodium knowlesi infections
Authors: T. Thurai Rathnam Jeyamalar , Grigg Matthew J. , Dini Saber , William Timothy , Sakam Sitti Saimah , Cooper Daniel J. , Rajahram Giri S. , Barber Bridget E. , Anstey Nicholas M. , Haghiri Ali , Rajasekhar Megha , Simpson Julie A. 
Published: February 2023

Abstract
Background
The incidence of zoonotic Plasmodium knowlesi infections in humans is rising in Southeast Asia, leading to clinical studies to monitor the efficacy of anti-malarial treatments for knowlesi malaria. One of the key outcomes of anti-malarial drug efficacy is parasite clearance. For Plasmodium falciparum, parasite clearance is typically estimated using a two-stage method, that involves estimating parasite clearance for individual patients followed by pooling of individual estimates to derive population estimates. An alternative approach is Bayesian hierarchical modelling which simultaneously analyses all parasite-time patient profiles to determine parasite clearance. This study compared these methods for estimating parasite clearance in P. knowlesi treatment efficacy studies, with typically fewer parasite measurements per patient due to high susceptibility to anti-malarials.

Methods
Using parasite clearance data from 714 patients with knowlesi malaria and enrolled in three trials, the Worldwide Antimalarial Resistance Network (WWARN) Parasite Clearance Estimator (PCE) standard two-stage approach and Bayesian hierarchical modelling were compared. Both methods estimate the parasite clearance rate from a model that incorporates a lag phase, slope, and tail phase for the parasitaemia profiles.

Results
The standard two-stage approach successfully estimated the parasite clearance rate for 678 patients, with 36 (5%) patients excluded due to an insufficient number of available parasitaemia measurements. The Bayesian hierarchical estimation method was applied to the parasitaemia data of all 714 patients. Overall, the Bayesian method estimated a faster population mean parasite clearance (0.36/h, 95% credible interval [0.18, 0.65]) compared to the standard two-stage method (0.26/h, 95% confidence interval [0.11, 0.46]), with better model fits (compared visually). Artemisinin-based combination therapy (ACT) is more effective in treating P. knowlesi than chloroquine, as confirmed by both methods, with a mean estimated parasite clearance half-life of 2.5 and 3.6 h, respectively using the standard two-stage method, and 1.8 and 2.9 h using the Bayesian method.

Conclusion
For clinical studies of P. knowlesi with frequent parasite measurements, the standard two-stage approach (WWARN’s PCE) is recommended as this method is straightforward to implement. For studies with fewer parasite measurements per patient, the Bayesian approach should be considered. Regardless of method used, ACT is more efficacious than chloroquine, confirming the findings of the original trials.
Safety and efficacy of first-in-man intrathecal injection of human astrocytes (AstroRx®) in ALS patients: phase I/IIa clinical trial results
Authors: Gotkine Marc , Caraco Yoseph , Lerner Yossef , Blotnick Simcha , Wanounou Maor , Slutsky Shalom Guy , Chebath Judith , Kuperstein Graciela , Estrin Elena , Ben-Hur Tamir , Hasson Arik , Molakandov Kfir , Sonnenfeld Tehila , Stark Yafit , Revel Ariel , Revel Michel , Izrael Michal 
Published: February 2023

Abstract
Background
Malfunction of astrocytes is implicated as one of the pathological factors of ALS. Thus, intrathecal injection of healthy astrocytes in ALS can potentially compensate for the diseased astrocytes. AstroRx® is an allogeneic cell-based product, composed of healthy and functional human astrocytes derived from embryonic stem cells. AstroRx® was shown to clear excessive glutamate, reduce oxidative stress, secrete various neuroprotective factors, and act as an immunomodulator. Intrathecal injection of AstroRx® to animal models of ALS slowed disease progression and extended survival. Here we report the result of a first-in-human clinical study evaluating intrathecal injection of AstroRx® in ALS patients.

Methods
We conducted a phase I/IIa, open-label, dose-escalating clinical trial to evaluate the safety, tolerability, and therapeutic effects of intrathecal injection of AstroRx® in patients with ALS. Five patients were injected intrathecally with a single dose of 100 × 106 AstroRx® cells and 5 patients with 250 × 106 cells (low and high dose, respectively). Safety and efficacy assessments were recorded for 3 months pre-treatment (run-in period) and 12 months post-treatment (follow-up period).

Results
A single administration of AstroRx® at either low or high doses was safe and well tolerated. No adverse events (AEs) related to AstroRx® itself were reported. Transient AEs related to the Intrathecal (IT) procedure were all mild to moderate. The study demonstrated a clinically meaningful effect that was maintained over the first 3 months after treatment, as measured by the pre-post slope change in ALSFRS-R. In the 100 × 106 AstroRx® arm, the ALSFRS-R rate of deterioration was attenuated from − 0.88/month pre-treatment to − 0.30/month in the first 3 months post-treatment (p = 0.039). In the 250 × 106 AstroRx® arm, the ALSFRS-R slope decreased from − 1.43/month to − 0.78/month (p = 0.0023). The effect was even more profound in a rapid progressor subgroup of 5 patients. No statistically significant change was measured in muscle strength using hand-held dynamometry and slow vital capacity continued to deteriorate during the study.

Conclusions
Overall, these findings suggest that a single IT administration of AstroRx® to ALS patients at a dose of 100 × 106 or 250 × 106 cells is safe. A signal of beneficial clinical effect was observed for the first 3 months following cell injection. These results support further investigation of repeated intrathecal administrations of AstroRx®, e.g., every 3 months.
Trial Registration: NCT03482050.
Venous thromboembolism after arthroscopic shoulder surgery: a systematic review
Authors: Li Tao , Li Yinghao , Zhang Linmin , Pang Long , Tang Xin , Zhu Jing 
Published: February 2023

Abstract
Purpose
To summarize the incidence, risk factors, diagnosis methods, prophylaxis methods, and treatment of venous thromboembolism (VTE) following arthroscopic shoulder surgery.

Methods
Literature on VTE after arthroscopic shoulder surgeries was summarized, and all primary full-text articles reporting at least 1 case of deep vein thrombosis (DVT) or pulmonary embolism (PE) after arthroscopic shoulder surgeries were included. Articles were critically appraised and systematically analyzed to determine the incidence, risk factors, diagnosis, prophylaxis, and management of VTE following arthroscopic shoulder surgeries.

Results
This study included 42 articles in which the incidence of VTE ranges from 0 to 5.71% and the overall incidence was 0.26%. Most VTE events took place between the operation day and the 14th day after the operation (35/51). Possible risk factors included advanced age (> 70 years), obesity (BMI ≥ 30 kg/m2), diabetes mellitus, thrombophilia, history of VTE, prolonged operation time, hormone use, and immobilization after surgery. The most common prophylaxis method was mechanical prophylaxis (13/15). No statistical difference was detected when chemoprophylaxis was applied. The management included heparinization followed by oral warfarin, warfarin alone and rivaroxaban, a direct oral anticoagulant.

Conclusion
Based on the included studies, the incidence rate of VTE after arthroscopic shoulder surgeries is relatively low. The risk factors for VTE are still unclear. CT/CTA and ultrasound were the mainstream diagnosis methods for PE and DVT, respectively. Current evidence shows that chemical prophylaxis did not deliver significant benefits, since none of the existing studies reported statistically different results. High-quality studies focusing on the prophylaxis and management of VTE population undergoing arthroscopic shoulder surgeries should be done in the future.
Changes in epidemiological characteristics of knee arthroplasty in eastern, northern and central China between 2011 and 2020
Authors: Sun Weiyi , Yuwen Peizhi , Yang Xuemei , Chen Wei , Zhang Yingze 
Published: February 2023

Abstract
Objective
To explore changes in the epidemiological and clinical characteristics of patients who underwent knee arthroplasty (KA) over a 10-year period in China.

Methods
Medical records of patients with knee osteoarthritis (KOA), who underwent primary unilateral KA in 5 level I center hospitals in China between January 2011 and December 2020, were retrospectively reviewed and analyzed. To more clearly define changes over the years, patients were divided into two groups according to time of admission at 5-year intervals. Age, sex, body mass index (BMI), Kellgren–Lawrence (K–L) classification, comorbid diseases, surgical procedures, hospital stay, and hospitalization costs were compared between the two groups.

Results
A total of 23,610 patients with KOA (5400 male and 18,210 females; mean age: 65.7 ± 7.6 years) who underwent primary unilateral KA were included. The number of KAs increased in recent years (group A, n = 7606 vs. group B, n = 16,004). Significant differences were noted in age, sex, BMI, K–L classification, comorbidities, surgical procedures, hospital stay, and hospitalization costs between the two periods (P < 0.05). More than three-quarters of KA cases involved females, and the age at surgery tended to be younger than that reported in foreign countries. In group B, the proportion of overweight and grade III, number of comorbidities, and unicompartmental knee arthroplasty patients increased compared to that in group A; however, hospitalization costs and length of hospital stay decreased.

Conclusions
Results suggested that the epidemiological characteristics of patients undergoing KA have changed over time. An analysis of the epidemiological characteristics of patients undergoing KA treatment may provide a scientific basis for the prevention and control of KOA.