bluuebunny/crossref_metadata_2025_split huggingface dataset:
Automated assessment of foot elevation in adults with hereditary spastic paraplegia using inertial measurements and machine learning
Authors: Ollenschläger Malte , Höfner Patrick , Ullrich Martin , Kluge Felix , Greinwalder Teresa , Loris Evelyn , Regensburger Martin , Eskofier Bjoern M. , Winkler Jürgen , Gaßner Heiko 
Published: August 2023

Abstract
Background
Hereditary spastic paraplegias (HSPs) cause characteristic gait impairment leading to an increased risk of stumbling or even falling. Biomechanically, gait deficits are characterized by reduced ranges of motion in lower body joints, limiting foot clearance and ankle range of motion. To date, there is no standardized approach to continuously and objectively track the degree of dysfunction in foot elevation since established clinical rating scales require an experienced investigator and are considered to be rather subjective. Therefore, digital disease-specific biomarkers for foot elevation are needed.

Methods
This study investigated the performance of machine learning classifiers for the automated detection and classification of reduced foot dorsiflexion and clearance using wearable sensors. Wearable inertial sensors were used to record gait patterns of 50 patients during standardized 4 $$\times$$
×
10 m walking tests at the hospital. Three movement disorder specialists independently annotated symptom severity. The majority vote of these annotations and the wearable sensor data were used to train and evaluate machine learning classifiers in a nested cross-validation scheme.

Results
The results showed that automated detection of reduced range of motion and foot clearance was possible with an accuracy of 87%. This accuracy is in the range of individual annotators, reaching an average accuracy of 88% compared to the ground truth majority vote. For classifying symptom severity, the algorithm reached an accuracy of 74%.

Conclusion
Here, we show that the present wearable gait analysis system is able to objectively assess foot elevation patterns in HSP. Future studies will aim to improve the granularity for continuous tracking of disease severity and monitoring therapy response of HSP patients in a real-world environment.
Analysis of the genetic contribution to thoracic aortic aneurysm or dissection in a prospective cohort of patients with familial and sporadic cases in East China
Authors: Duan Yanyu , Xiong Jianxian , Lai Zhenghong , Zhong Yiming , Tian Chengnan , Du Zhiming , Luo Zhifang , Yu Junjian , Li Wentong , Xu Weichang , Wang Yabing , Ding Ting , Zhong Xuehong , Pan Mengmeng , Qiu Yu , Lan Xuemei , Chen Taihua , Li Peijun , Liu Kang , Gao Meng , Hu Yanqiu , Liu Ziyou 
Published: August 2023

Abstract
Background
Thoracic aortic aneurysm or dissections (TAADs) represent a group of life-threatening diseases. Genetic aetiology can affect the age of onset, clinical phenotype, and timing of intervention. We conducted a prospective trial to determine the prevalence of pathogenic variants in TAAD patients and to elucidate the traits related to harbouring the pathogenic variants. One hundred and one unrelated TAAD patients underwent genetic sequencing and analysis for 23 TAAD-associated genes using a targeted PCR and next-generation sequencing-based panel.

Results
A total of 47 variants were identified in 52 TAAD patients (51.5%), including 5 pathogenic, 1 likely pathogenic and 41 variants of uncertain significance. The pathogenic or likely pathogenic (P/LP) variants in 4 disease-causing genes were carried by 1 patient with familial and 5 patients with sporadic TAAD (5.9%). In addition to harbouring one variant causing familial TAAD, the FBN1 gene harboured half of the P/LP variants causing sporadic TAAD. Individuals with an age of onset less than 50 years or normotension had a significantly increased genetic risk.

Conclusions
TAAD patients with a younger age at diagnosis or normotension were more likely to carry a P/LP variant; thus, routine genetic testing will be beneficial to a better prognosis through genetically personalized care prior to acute rupture or dissection.
Economic burden of adult patients with β-thalassaemia major in mainland China
Authors: Zhen Xuemei , Ming Jing , Zhang Runqi , Zhang Shuo , Xie Jing , Liu Baoguo , Wang Zijing , Sun Xiaojie , Shi Lizheng 
Published: August 2023

Abstract
Background
β-thalassaemia major poses a substantial economic burden, especially in adults. We aimed to estimate the economic burden of adult patients with β-thalassaemia major from a societal perspective using the real-world data. According to the clinical guideline, we also estimated the annual medical costs for patients with the same body weight and calculated the lifetime medical costs over 50 years in mainland China.

Methods
This was a retrospective cross-sectional study. An online survey with snowball sampling covering seven provinces was conducted. We extracted patient demographics, caregiver demographics, disease and therapy information, caring burden, and costs for adult patients diagnosed with β-thalassaemia major and their primary caregivers. In the real world, we estimated the annual direct medical cost, direct nonmedical cost, and indirect cost. In addition, we calculated the annual direct medical cost and lifetime direct medical cost by weight with discounted and undiscounted rates according to the clinical guideline.

Results
Direct medical costs was the main driver of total cost, with blood transfusion and iron chelation therapy as the most expensive components of direct medical cost. In addition, adult patients with β-thalassaemia major weighing 56 kg were associated with an increase of $2,764 in the annual direct medical cost using the real-world data. The undiscounted and discounted (5% discount rate) total lifetime treatment costs were $518,871 and $163,441, respectively.

Conclusions
Patients with β-thalassaemia major often encounter a substantial economic burden in mainland China. Efforts must be made to help policymakers develop effective strategies to reduce the burden and pevalence of thalassaemia.
Identification of two novel SALL1 mutations in chinese families with townes-brocks syndrome and literature review
Authors: Wang Zhendong , Sun Zhenfu , Diao Yujie , Wang Zhouyang , Yang Xiangdong , Jiang Bei , Wu Yumei , Liu Guangyi 
Published: August 2023

Abstract
Background
Townes-Brocks syndrome is a rare autosomal dominant genetic syndrome caused by mutations in SALL1. The clinical features of Townes-Brocks syndrome are highly heterogonous. Identification of new SALL1 mutations and study of the relation between SALL1 mutations and clinical features can facilitate diagnosis of Townes-Brocks syndrome.

Methods
We collected clinical data and blood samples of the two patients and their family members for whole-exome sequencing and Sanger sequencing. Prediction analysis of the SALL1variation protein structure was achieved using Alphafold. The clinical materials and gene sequencing results were analyzed. The clinical materials and gene sequencing results were analyzed. The related literature of Townes-Brocks syndrome were searched and the genotype-renal phenotype analysis was performed combined with this two cases.

Results
Based on the clinical features and gene sequencing results, the two patients were diagnosed as Townes-Brocks syndrome. Two novel SALL1 mutations (c.878-887del and c.1240G > T) were identified, both of which were pathogenic mutations. The correlation between genotypes and renal phenotypes in Townes-Brocks syndrome patients caused by SALL1 mutation were summarized.

Conclusion
This study identified two novel mutations and provided new insights into the correlation of genotypes and renal phenotypes of Townes-Brocks syndrome.
Lumbar vertebral canal stenosis due to marked bone overgrowth after routine hemilaminectomy in a dog
Authors: Tavola Francesca , Ruggeri Marco , Carrera Ines , Pumarola Martí , Alegria Pablo Menendez , Tauro Anna 
Published: August 2023

Abstract
Background
Bone overgrowth after decompressive surgery for lumbar stenosis resulting in recurrence of neurological signs has not been reported in veterinary literature. However, there are few cases described in human medicine.

Case presentation
A 13-month-old entire female dog, a crossbreed between a Springer Spaniel and a Border Collie, weighing 24 kg, was referred with a 5-day history of progressive spastic paraplegia, indicative of a T3-L3 myelopathy. Magnetic resonance (MR) imaging revealed a right-sided L2-L3 compressive extradural lesion, compatible with epidural haemorrhage, which was confirmed by histopathology. The lesion was approached via right-sided L2-L3 hemilaminectomy and was successfully removed. One-year postoperatively the dog re-presented with pelvic limb ataxia. MR and computed tomography (CT) images demonstrated excessive vertebral bone formation affecting the right articular processes, ventral aspect of the spinous process of L2-L3, and contiguous vertebral laminae, causing spinal cord compression. Revision surgery was performed, and histopathology revealed normal or reactive osseous tissue with a possible chondroid metaplasia and endochondral ossification, failing to identify a definitive reason for the bone overgrowth. Nine-month postoperatively, imaging studies showed a similar vertebral overgrowth, resulting in minimal spinal cord compression. The patient remained stable with mild proprioceptive ataxia up until the last follow-up 18 months post-revision surgery.

Conclusion
This is the first report in the veterinary literature of bone overgrowth after lumbar hemilaminectomy which resulted in neurological deficits and required a revision decompressive surgery.
Physicians in police tactical teams – ethical considerations
Authors: de Valence Timothee , Suppan Laurent 
Published: August 2023

AbstractHigh-profile mass shootings, terrorist attacks, and experience acquired during recent conflicts have led to a shift in police tactics, who now follow an aggressive approach to immediately neutralize the threat in addition to providing early tactical medical care. A growing number of police tactical teams now include physicians in their ranks to increase the level of forward care. Many ethical questions arise from having physicians on police tactical teams, such as the notion of risk, the use of force, and the ultimate role the physician is expected to play. Having a physician in such a team may be an invaluable asset to increase the team’s safety and allow for advanced forward care, however, this requires two important conditions. The first is that the role of the physician is clearly defined and that what is expected of him is in line with medical ethics, while the second is extensive tactical training with the team to collaborate flawlessly in this complex, high-stress environment.
Determinants of incident atherosclerotic cardiovascular disease events among individuals with type 2 diabetic microvascular complications in the UK: a prospective cohort study
Authors: Wang Yaxin , Bulloch Gabriella , Huang Yu , Liang Yingying , Du Zijing , Wu Guanrong , Fang Ying , Hu Yijun , Shang Xianwen , Zhu Zhuoting , Zhang Xiayin , Yang Xiaohong , Yu Honghua 
Published: August 2023

Abstract
Objective
To evaluate the association of atherosclerotic cardiovascular disease (ASCVD) risk factors with incident ASCVD events among type 2 diabetes (T2D) individuals with microvascular complications.

Methods
We included T2D participants with only microvascular complications from the UK Biobank cohort at baseline (2006–2010). Multivariable-adjusted Cox proportional hazards models were used to study the association between ASCVD risk factors with adjudicated incident ASCVD in T2D participants with only microvascular complications. A restricted cubic spline approach was employed to evaluate potential nonlinear associations between ASCVD risk factors and ASCVD.

Results
We studied 4,129 T2D individuals with microvascular complications at baseline. Over a median follow-up of 11.7 years, a total of 1,180 cases of incident ASCVD were documented, of which 1,040 were CHD, 100 were stroke, and 40 were both CHD and stroke events. After multivariable-adjustment, high-density lipoprotein cholesterol (HDL-C) level was linearly associated with a decreased risk of incident ASCVD [hazard ratio (HR): 0.49, 95% Confidence interval (CI): 0.32–0.75, Plinear = 0.011] and each 10 nmol/L increase of lipoprotein(a) [Lp(a)] level (HR: 1.02, 95% CI: 1.00-1.04, Plinear = 0.012) was linearly associated with an increased risk of incident ASCVD in T2D participants with only microvascular complications.

Conclusion
HDL-C levels and Lp(a) levels (per 10 nmol/L) showed an independent linear relation with ASCVD risk among T2D individuals with only microvascular complications at long-term follow-up.
Association of DNA methylation of vitamin D metabolic pathway related genes with colorectal cancer risk
Authors: Wang Yi-Fan , Li Lei , Deng Xue-Qing , Fang Yu-Jing , Zhang Cai-Xia 
Published: August 2023

Abstract
Background
Vitamin D might have anti-tumor effect, which is affected by the genes related to vitamin D metabolic pathway. Epigenetic mechanism may affect the expression level of vitamin D metabolic pathway related genes, then plays an important role in the occurrence and development of colorectal cancer. To date, no study has reported on the association between blood-based DNA methylation level of vitamin D metabolic pathway related genes and colorectal cancer risk.

Methods
A case–control study was conducted including 102 colorectal cancer cases and 102 sex- and age-frequency-matched controls in Guangzhou, China. CpG islands in the VDR, CYP24A1, CYP27B1 and CYP2R1 genes were chosen for DNA methylation analysis by MethylTarget sequencing. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of DNA methylation levels for colorectal cancer. Taking the point with the largest Youden index as the boundary value, the cumulative methylation levels of vitamin D metabolic pathway related genes were divided into hypomethylation and hypermethylation. Unconditional multivariable logistical regression model was used to calculate the adjusted odds ratio (aOR) and 95% confidence intervals (95% CIs) after adjusting for potential confounders.

Results
Among 153 CpG sites, 8 CpG sites were significantly different between the cases and the controls. The cumulative methylation level of all CpG sites in CYP2R1 was inversely associated with the risk of colorectal cancer (aOR, 0.49; 95% CI, 0.26–0.91). However, no significant association was found between cumulative methylation levels of all CpG sites in VDR, CYP24A1 and CYP27B1 and colorectal cancer risk. Significant inverse association was observed between cumulative methylation level of significant CpG sites in VDR (aOR, 0.28; 95% CI, 0.16–0.51) and CYP24A1 (aOR, 0.19; 95% CI, 0.09–0.40) and colorectal cancer risk. There were no significant associations between cumulative methylation levels of significant CpG sites in CYP2R1 and CYP27B1 and colorectal cancer risk.

Conclusions
This study indicated that the cumulative methylation levels of significant CpG sites in VDR and CYP24A1 and all CpG sites in CYP2R1 were inversely associated with colorectal cancer risk.
Cyclosporine for omalizumab-refractory chronic urticaria: a report of five cases
Authors: LaCava Anthony F. , Fadugba Olajumoke O. 
Published: August 2023

Abstract
Background
While both the AAAAI/ACAAI and the EAACI/GA2LEN/EuroGuiDerm/APAAACI guidelines recommend starting cyclosporine for patients with chronic urticaria who have had an inadequate response to omalizumab, many clinicians are hesitant to initiate cyclosporine due to paucity of clinical data. The objective of this study was to report real-life clinical outcomes in adult patients with chronic urticaria who had an inadequate response to omalizumab and were switched from omalizumab to cyclosporine. Medical records of adult patients with chronic urticaria who had an inadequate response with omalizumab and were later treated with cyclosporine were reviewed retrospectively. Data pertaining to treatment method, clinical response, and adverse effects were recorded.

Results/presentation of cases
Five patients with omalizumab-refractory chronic urticaria, three of whom also had angioedema and one with an inducible urticaria, were treated with low doses of oral cyclosporine (1–3 mg/kg/d). Four of five patients in this case series had complete resolution of symptoms with oral cyclosporine, while continuing other standard therapies. Systemic side effects occurred in three patients which prompted drug discontinuation in two patients.

Discussion
Cyclosporine alone was effective in inducing urticaria control in adult patients with chronic urticaria who had an inadequate response to omalizumab, though the impact of cyclosporine was limited by reversible adverse effects. Adverse effects were associated with pre-existing medical conditions. As novel chronic urticaria therapies are being investigated, this experience highlights the importance of uncovering chronic urticaria subtypes which tend to respond to cyclosporine, while providing alternative treatments with better tolerability.
Long-term persistence of piscine orthoreovirus-1 (PRV-1) infection during the pre-smolt stages of Atlantic salmon in freshwater
Authors: Kannimuthu Dhamotharan , Roh HyeongJin , Peñaranda Ma. Michelle D. , Wessel Øystein , Mæhle Stig , Berhe Ghebretnsae Dawit , Nordbø Joachim , Kvamme Bjørn Olav , Morton H. Craig , Grove Søren 
Published: August 2023

AbstractPiscine orthoreovirus (PRV) causes heart and skeletal muscle inflammation (HSMI) in farmed Atlantic salmon. During salmon production cycles, HSMI has predominantly been observed after seawater transfer. More recently, better surveillance and longitudinal studies have detected occurrences of PRV-1 in freshwater broodstock farms and hatcheries. However, very little is known about the viral kinetics of PRV-1 or disease development of HSMI during these pre-smolt stages. In this study, we conducted a long-term PRV-1 challenge experiment to examine the profile of viral load, infectiousness and/or clearance in Atlantic salmon during their development from fry to parr stage. Atlantic salmon fry (mean weight: 1.1 ± 0.19 g) were infected with PRV-1 (high virulent variant) via intraperitoneal (IP) injection. The viral load reached a peak at 2–4 weeks post-challenge (wpc) in heart and muscle tissues. The virus was detected at relatively high levels in whole blood, spleen, and head kidney tissues until 65 wpc. Heart and muscle lesions typical of HSMI were clearly observed at 6 and 8 wpc but then subsided afterwards resolving inflammation. Innate and adaptive immune responses were elicited during the early/acute phase but returned to basal levels during the persistent phase of infection. Despite achieving high viremia, PRV-1 infection failed to cause any mortality during the 65-week virus challenge period. Cohabitation of PRV-1 infected fish (10 and 31 wpc) with naïve Atlantic salmon fry resulted in very low or no infection. Moreover, repeated chasing stress exposures did not affect the viral load or shedding of PRV-1 at 26 and 44 wpc. The present findings provide knowledge about PRV-1 infection in juvenile salmon and highlight the importance of continued monitoring and management to prevent and mitigate the PRV-1 infection in freshwater facilities.
The therapeutic potential for targeting CSE/H2S signaling in macrophages against Escherichia coli infection
Authors: Fu Shaodong , Wang Zhenglei , Han Xiangan , Xu Yuanyuan , Miao Jinfeng 
Published: August 2023

AbstractMacrophages play a pivotal role in the inflammatory response to the zoonotic pathogen E. coli, responsible for causing enteric infections. While considerable research has been conducted to comprehend the pathogenesis of this disease, scant attention devoted to host-derived H2S. Herein, we reported that E. coli infection enhanced the expression of CSE in macrophages, accompanied by a significantly increased inflammatory response. This process may be mediated by the involvement of excessive autophagy. Inhibition of AMPK or autophagy with pharmacological inhibitors could alleviate the inflammation. Additionally, cell model showed that the mRNA expression of classic inflammatory factors (Il-1β, Il-6), macrophage polarization markers (iNOS, Arg1) and ROS production was significantly down-regulated after employing CSE specific inhibitor PAG. And PAG is capable of inhibiting excessive autophagy through the LKB1-AMPK-ULK1 axis. Interestingly, exogenous H2S could suppress inflammation response. Our study emphasizes the importance of CSE in regulating the macrophage-mediated response to E. coli. Increased CSE in macrophages leads to excessive inflammation, which should be considered a new target for drug development to treat intestinal infection.
Performance of RIS-aided near-field localization under beams approximation from real hardware characterization
Authors: Rahal Moustafa , Denis Benoît , Keykhosravi Kamran , Keskin Musa Furkan , Uguen Bernard , Alexandropoulos George C. , Wymeersch Henk 
Published: August 2023

AbstractThe technology of reconfigurable intelligent surfaces (RISs) has been showing promising potential in a variety of applications relying on Beyond-5G networks. RIS can indeed provide fine channel flexibility to improve communication quality of service (QoS) or restore localization capabilities in challenging operating conditions, while conventional approaches fail (e.g., due to insufficient infrastructure, severe radio obstructions). In this paper, we tackle a general low-complexity approach for optimizing the precoders that control such reflective surfaces under hardware constraints. More specifically, it allows the approximation of any desired beam pattern using a pre-characterized lookup table of feasible complex reflection coefficients for each RIS element. The proposed method is first evaluated in terms of beam fidelity for several examples of RIS hardware prototypes. Then, by means of a theoretical bounds analysis, we examine the impact of RIS beams approximation on the performance of near-field downlink positioning in non-line-of-sight conditions, while considering several RIS phase profiles (including directional, random and localization-optimal designs). Simulation results in a canonical scenario illustrate how the introduced RIS profile optimization scheme can reliably produce the desired RIS beams under realistic hardware limitations. They also highlight its sensitivity to both the underlying hardware characteristics and the required beam kinds in relation to the specificity of RIS-aided localization applications.