bluuebunny/crossref_metadata_2025_split huggingface dataset:
Instrumented assessment of gait disturbance in PMM2-CDG adults: a feasibility analysis
Authors: Cirnigliaro Lara , Pettinato Fabio , Valle Maria Stella , Casabona Antonino , Fiumara Agata , Vecchio Michele , Amico Valerio , Rizzo Renata , Jaeken Jaak , Barone Rita , Cioni Matteo 
Published: February 2024

Abstract
Background
Congenital disorders of glycosylation (CDG) are genetic diseases caused by impaired synthesis of glycan moieties linked to glycoconjugates. Phosphomannomutase 2 deficiency (PMM2-CDG), the most frequent CDG, is characterized by prominent neurological involvement. Gait disturbance is a major cause of functional disability in patients with PMM2-CDG. However, no specific gait assessment for PMM2-CDG is available. This study analyses gait-related parameters in PMM2-CDG patients using a standardized clinical assessment and instrumented gait analysis (IGA).

Results
Seven adult patients with a molecular diagnosis of PMM2-CDG were followed-up from February 2021 to December 2022 and compared to a group of healthy control (HC) subjects, matched for age and sex. Standardized assessment of disease severity including ataxia and peripheral neuropathy along with isometric muscle strength and echo-biometry measurements at lower limbs were performed. IGA spatiotemporal parameters were obtained by means of a wearable sensor in basal conditions. PMM2-CDG patients displayed lower gait speed, stride length, cadence and symmetry index, compared to HC. Significant correlations were found among the used clinical scales and between disease severity (NCRS) scores and the gait speed measured by IGA. Variable reduction of knee extension strength and a significant decrease of lower limb muscle thickness with conserved echo intensity were found in PMM2-CDG compared to HC.

Conclusions
The study elucidates different components of gait disturbance in PMM2-CDG patients and shows advantages of using wearable sensor-based IGA in this frame. IGA parameters may potentially serve as quantitative measures for follow-up or outcome quantification in PMM2-CDG.
Reducing agalsidase beta infusion time in Fabry patients: low incidence of antibody formation and infusion-associated reactions in an Italian multicenter study
Authors: Mignani Renzo , Americo Claudio , Aucella Filippo , Battaglia Yuri , Cianci Vittoria , Sapuppo Annamaria , Lanzillo Chiara , Pennacchiotti Fabio , Tartaglia Luciano , Marchi Giacomo , Pieruzzi Federico 
Published: February 2024

Abstract
Background
Fabry disease is a rare progressive X-linked lysosomal storage disease caused by mutations in the GLA gene that encodes α-galactosidase A. Agalsidase beta is a recombinant enzyme replacement therapy authorized in Europe at a standard dose of 1.0 mg/kg intravenously every other week at an initial infusion rate of ≤ 0.25 mg/min until patient tolerance is established, after which the infusion rate may be increased gradually. However, specific practical guidance regarding the progressive reduction in infusion time is lacking. This study investigated a new and specific protocol for reducing agalsidase beta infusion time in which a stable dosage of 15 mg/h is infused for the first four months, and the infusion rate is increased progressively from 15 to 35 mg/h for the subsequent four infusions. The shortest infusion time is reached after six months and maintained thereafter. The incidence of infusion-associated reactions (IARs) and the development of anti-drug antibodies were analyzed, and the disease burden and the clinical evolution of the disease at 12 months were evaluated.

Results
Twenty-five of the 31 patients were naïve to enzyme or chaperone treatment at baseline and six patients had been switched from agalsidase alfa. The reduced infusion time protocol was well tolerated. Only one patient exhibited an IAR, with mild symptoms that resolved with low-dose steroids. Six patients globally seroconverted during treatment (4 with a classic phenotype and 2 with late-onset disease). All but three patients were seronegative at month 12. All patients were stable at the study’s end (FAbry STabilization indEX value < 20%); reducing infusion time did not negatively impact clinical outcomes in any patient. The perceived medical assessment showed that the quality of life of all patients improved.

Conclusions
The study demonstrates that reducing agalsidase beta infusion time is possible and safe from both an immunogenic and clinical point of view. The use of a low infusion rate in the first months when the probability of onset of the development of antibodies is higher contributed to very limited seroconversion to antibody-positive status.
Aneuploid serves as a prognostic marker and favors immunosuppressive microenvironment in ovarian cancer
Authors: Du Ming , Cai Qingqing , Sun Jiaan , Zhang Mingxing , Zhang Shuo , Liu Xiaoxia , Zhang Mengyu , Zhang Xiaoyan 
Published: February 2024

AbstractOvarian cancer is the most lethal gynecologic neoplasm, and most patients experience recurrence and chemoresistance. Even the promising immunotherapy showed limited efficacy in ovarian cancer, probably due to the immunosuppressive microenvironment. However, the behind mechanisms of the immune exclusion or cold phenotype in ovarian cancer still remain to be explored. As a cancer dominated by copy number variations instead of mutations, ovarian cancer contains a high fraction of aneuploid, which might correlate with immune inhibition. Nevertheless, whether or how aneuploid affects ovarian cancer is still unclear. For exploring the role of aneuploid cancer cells and the potential ploidy-immune relationship, herein, the ploidy information was first comprehensively analyzed combining the karyotype data and copy number variation data obtained from Mitelman and cBioPortal databases, respectively. Ovarian cancer showed strong ploidy heterogeneity, with high fraction of aneuploid and recurrent arm-level and whole chromosome changes. Furthermore, clinical parameters were compared between the highly-aneuploid and the near-diploid ovarian cancers. Aneuploid indicated high grade, poor overall survival and poor disease-free survival in ovarian cancer. To understand the biofunction affected by aneuploid, the differentially expressed genes between the highly-aneuploid and the near-diploid groups were analyzed. Transcription data suggested that aneuploid cancer correlated with deregulated MHC expression, abnormal antigen presentation, and less infiltration of macrophages and activated T cells and higher level of T cell exclusion. Furthermore, the ploidy-MHC association was verified using the Human Protein Atlas database. All these data supported that aneuploid might be promising for cancer management and immune surveillance in ovarian cancer.
USP40 promotes hepatocellular carcinoma cell proliferation, migration and stemness by deubiquitinating and stabilizing Claudin1
Authors: Wu Qingsong , Qiu Yuanyuan , Guo Jinhui , Yuan Zibo , Yang Yingnan , Zhu Qingwei , Zhang Zhe , Guo Junwei , Wu Yanfang , Zhang Junyu , Huang Dongsheng , Tu Kangsheng , Hu Xiaoge 
Published: February 2024

Abstract
Background
Hepatocellular carcinoma (HCC) is a prevalent malignant tumor that poses a major threat to people’s lives and health. Previous studies have found that multiple deubiquitinating enzymes are involved in the pathogenesis of HCC. The purpose of this work was to elucidate the function and mechanism of the deubiquitinating enzyme USP40 in HCC progression.

Methods
The expression of USP40 in human HCC tissues and HCC cell lines was investigated using RT-qPCR, western blotting and immunohistochemistry (IHC). Both in vitro and in vivo experiments were conducted to determine the crucial role of USP40 in HCC progression. The interaction between USP40 and Claudin1 was identified by immunofluorescence, co-immunoprecipitation and ubiquitination assays.

Results
We discovered that USP40 is elevated in HCC tissues and predicts poor prognosis in HCC patients. USP40 knockdown inhibits HCC cell proliferation, migration and stemness, whereas USP40 overexpression shows the opposite impact. Furthermore, we confirmed that Claudin1 is a downstream gene of USP40. Mechanistically, USP40 interacts with Claudin1 and inhibits its polyubiquitination to stabilize Claudin1 protein.

Conclusions
Our study reveals that USP40 enhances HCC malignant development by deubiquitinating and stabilizing Claudin1, suggesting that targeting USP40 may be a novel approach for HCC therapy.
Health economic evaluation of a nurse-assisted online eye screening in home healthcare to reduce avoidable vision impairment (iScreen): study protocol for a cluster randomized controlled trial
Authors: Rooth Vera , van der Aa Hilde , Wisse Robert P. L. , Maarsingh Otto R. , Koopmanschap Marc , Keunen Jan E. E. , Vermeulen Hester , Klaver Caroline C. W. , Janssen Gabriëlle , van Rens Ger H. M. B. , van Nispen Ruth M. A. 
Published: February 2024

Abstract
Background
Among older people undiagnosed and untreated vision impairment and blindness are common. The leading causes are uncorrected refractive errors and cataracts. Vision problems are associated with a lower quality of life, several health problems, and a higher chance of falling accidents and fractures. To eliminate avoidable vision impairment and blindness, targeted eye screening programs are recommended. Older patients, receiving home healthcare, have not yet been considered as a population at risk who could benefit from eye screening.

Methods
A cluster-randomized controlled trial will be conducted to investigate the cost-effectiveness and cost-utility of online nurse-assisted eye screening in home healthcare, compared to care as usual, in reducing avoidable vision impairment. A healthcare and societal perspective will be used. The study will be performed in collaboration with several home healthcare organizations in the Netherlands. The online eye screening consists of near and distance visual acuity, followed by an Amsler grading test. Measurements in both groups will take place at baseline and after 6 and 12 months of follow-up. A total of 240 participants will be recruited. Older men and women (65 +), who receive home-based nursing and are cognitively able to participate, will be included. The primary outcome will be the change of two lines or more on the Colenbrander-1 M visual acuity chart between baseline and 12-month follow-up.

Discussion
An eye screening for populations at risk contributes to the detection of undiagnosed and untreated vision impairment. This may reduce the health-related consequences of vision loss and the high economic burden associated with vision impairment.

Trial registration
ClinicalTrials.gov NCT06058637. Registered on 27 September 2023.
Unveiling the sound of the cognitive status: Machine Learning-based speech analysis in the Alzheimer’s disease spectrum
Authors: García-Gutiérrez Fernando , Alegret Montserrat , Marquié Marta , Muñoz Nathalia , Ortega Gemma , Cano Amanda , De Rojas Itziar , García-González Pablo , Olivé Clàudia , Puerta Raquel , García-Sanchez Ainhoa , Capdevila-Bayo María , Montrreal Laura , Pytel Vanesa , Rosende-Roca Maitee , Zaldua Carla , Gabirondo Peru , Tárraga Lluís , Ruiz Agustín , Boada Mercè , Valero Sergi 
Published: February 2024

Abstract
Background
Advancement in screening tools accessible to the general population for the early detection of Alzheimer’s disease (AD) and prediction of its progression is essential for achieving timely therapeutic interventions and conducting decentralized clinical trials. This study delves into the application of Machine Learning (ML) techniques by leveraging paralinguistic features extracted directly from a brief spontaneous speech (SS) protocol. We aimed to explore the capability of ML techniques to discriminate between different degrees of cognitive impairment based on SS. Furthermore, for the first time, this study investigates the relationship between paralinguistic features from SS and cognitive function within the AD spectrum.

Methods
Physical-acoustic features were extracted from voice recordings of patients evaluated in a memory unit who underwent a SS protocol. We implemented several ML models evaluated via cross-validation to identify individuals without cognitive impairment (subjective cognitive decline, SCD), with mild cognitive impairment (MCI), and with dementia due to AD (ADD). In addition, we established models capable of predicting cognitive domain performance based on a comprehensive neuropsychological battery from Fundació Ace (NBACE) using SS-derived information.

Results
The results of this study showed that, based on a paralinguistic analysis of sound, it is possible to identify individuals with ADD (F1 = 0.92) and MCI (F1 = 0.84). Furthermore, our models, based on physical acoustic information, exhibited correlations greater than 0.5 for predicting the cognitive domains of attention, memory, executive functions, language, and visuospatial ability.

Conclusions
In this study, we show the potential of a brief and cost-effective SS protocol in distinguishing between different degrees of cognitive impairment and forecasting performance in cognitive domains commonly affected within the AD spectrum. Our results demonstrate a high correspondence with protocols traditionally used to assess cognitive function. Overall, it opens up novel prospects for developing screening tools and remote disease monitoring.
Outcome of severe COVID-19: spotlight on fatigue, fatigability, multidomain complaints and pattern of cognitive deficits in a case series without prior brain dysfunction and without COVID-19-related stroke and/or cardiac arrest
Authors: Beaud Valérie , Crottaz-Herbette Sonia , Dunet Vincent , Knebel Jean-François , Bart Pierre-Alexandre , Clarke Stephanie 
Published: February 2024

Abstract
Background
Population-wide surveys and large-scale investigations highlighted the presence of cognitive deficits in the acute and postacute stages of severe COVID-19; a few studies documented their occurrence in cases without prior or COVID-19-related brain damage. The evolution of cognitive deficits in the latter population and their relationship to the post-COVID-19 fatigue syndrome are poorly understood.

Case presentation
We report the outcome at 12 months after severe COVID-19 involving an intensive care unit stay and mechanical ventilation in six (five Caucasian and one Asian) patients (age range: 53–71 years, mean age 61.7 ± 6.5 years) without history of prior brain dysfunction and without stroke and/or cardiac arrest during or after COVID-19. All patients reported pervading mental and physical fatigue as well as numerous multidomain complaints, which impacted everyday life. Individual patients described mental fatigability, apathy, and/or anxiety. Standardized neuropsychological tests revealed isolated symptoms of cognitive dysfunction or performance at the lower limit of the norm in the attentional, executive, and/or working memory domains in four of the six patients. Somatic scales documented dyspnoea, muscle weakness, olfactory disorder, and/or minor sleep problems in some, but not all, patients.

Conclusion
Fatigue, fatigability, multidomain complaints, cognitive difficulties, or dysfunction, as well as isolated neurobehavioral and/or psychiatric and/or somatic symptoms, tend to occur in the aftermath of severe COVID-19 and persist at 12 months, even in the absence of prior and/or COVID-19-related brain damage. This clinical situation, which impacts everyday life, calls for a detailed investigation of patients’ complaints, its neural underpinning, and an elaboration of specific rehabilitation programs.
Efficacy of the immediate adipose-derived stromal vascular fraction autograft on functional sensorimotor recovery after spinal cord contusion in rats
Authors: Ertlen Céline , Seblani Mostafa , Bonnet Maxime , Brezun Jean-Michel , Coyle Thelma , Sabatier Florence , Fuentes Stéphane , Decherchi Patrick , Serratrice Nicolas , Marqueste Tanguy 
Published: February 2024

Abstract
Background
Spinal cord injuries (SCI) lead to functional alteration with important consequences such as motor and sensory disorders. The repair strategies developed to date remain ineffective. The adipose tissue-derived stromal vascular fraction (SVF) is composed of a cocktail of cells with trophic, pro-angiogenic and immunomodulatory effects. Numerous therapeutic benefits were shown for tissue reconstitution, peripheral neuropathy and for the improvement of neurodegenerative diseases. Here, the therapeutic efficacy of SVF on sensorimotor recovery after an acute thoracic spinal cord contusion in adult rats was determined.

Method
Male Sprague Dawley rats (n = 45) were divided into 3 groups: SHAM (without SCI and treatment), NaCl (animals with a spinal lesion and receiving a saline injection through the dura mater) and SVF (animals with a spinal lesion and receiving a fraction of fat removed from adipocytes through the dura mater). Some animals were sacrificed 14 days after the start of the experiment to determine the inflammatory reaction by measuring the interleukin-1β, interleukin-6 and Tumor Necrosis Factor-α in the lesion area. Other animals were followed once a week for 12 weeks to assess functional recovery (postural and locomotor activities, sensorimotor coordination). At the end of this period, spinal reflexivity (rate-dependent depression of the H-reflex) and physiological adjustments (ventilatory response to metabosensitive muscle activation following muscle fatigue) were measured with electrophysiological tools.

Results
Compared to non-treated animals, results indicated that the SVF reduced the endogenous inflammation and increased the behavioral recovery in treated animals. Moreover, H-reflex depression and ventilatory adjustments to muscle fatigue were found to be comparable between SHAM and SVF groups.

Conclusion
Our results highlight the effectiveness of SVF and its high therapeutic potential to improve sensorimotor functions and to restore the segmental sensorimotor loop and the communication between supra- and sub-lesional spinal cord regions after traumatic contusion.

Graphical Abstract
Meta-analysis of elastic versus rigid fixation in the treatment of acute tibiofibular syndesmosis injury
Authors: Wang Qin , Liu Shuan , Wang Zhemin , Li Ao , Ding Jinhui 
Published: February 2024

Abstract
Objective
The objective of this study was to conduct a meta-analysis by synthesizing multiple literature sources to explore whether there are any differences between elastic fixation and rigid fixation in the treatment of acute tibiofibular syndesmosis injuries. The aim was to provide effective guidance for clinical treatment.

Methods
We conducted a comprehensive search across seven databases, including both Chinese and English, to include all studies related to the treatment of acute tibiofibular syndesmosis injuries with elastic fixation and rigid fixation published between January 1, 2013, and November 15, 2022. Following the PRISMA guidelines, we rigorously screened, assessed, and extracted data from the included studies. The outcome measures included AOFAS scores at 3, 6, and 12 months postoperatively; tibiofibular clear space (TBCS) and tibiofibular overlap distance (TBOL) at the early postoperative and 12-month follow-up; intraoperative blood loss; operative time; time to full weight-bearing postoperatively; and postoperative complications. Meta-analysis was performed using Review Manager 5.4.

Results
A total of 35 studies were included, comprising 16 randomized controlled trials and 19 retrospective cohort studies. The study population included 2120 cases, with 1044 cases in the elastic fixation group and 1076 cases in the rigid fixation group. The elastic fixation group had higher AOFAS scores at 3, 6, and 12 months postoperatively compared to the rigid fixation group. Although the elastic fixation group had a slightly larger TBCS than the rigid fixation group in the early postoperative period, the difference between the two groups became statistically insignificant at 12 months postoperatively. There was no statistically significant difference in TBOL between the two groups in the early postoperative period, but at 12 months, the elastic fixation group had a greater TBOL than the rigid fixation group. Additionally, the elastic fixation group had lower rates of postoperative local irritation, wound infection, and postoperative internal fixation loosening or rupture compared to the rigid fixation group. The rate of postoperative tibiofibular redislocation did not differ statistically between the two groups. The time to full weight-bearing was shorter in the elastic fixation group than in the rigid fixation group. Although the elastic fixation group had a slightly longer operative time, there was no statistically significant difference in intraoperative blood loss between the two groups.

Conclusion
Compared to rigid fixation, elastic fixation in the treatment of acute tibiofibular syndesmosis injuries offers several advantages, including better postoperative ankle joint function recovery, more precise anatomical reduction of the syndesmosis postoperatively, a lower incidence of postoperative complications, and shorter time to full weight-bearing postoperatively. These findings provide robust guidance for clinical treatment.
A cross-sectional analysis of the effectiveness of a nutritional support programme for people with tuberculosis in Southern Madagascar using secondary data from a non-governmental organisation
Authors: Franke Mara Anna , Emmrich Julius Valentin , Ranjaharinony Fierenantsoa , Ravololohanitra Onja Gabrielle , Andriamasy Harizaka Emmanuel , Knauss Samuel , Muller Nadine 
Published: February 2024

Abstract
Background
There is a strong, bi-directional link between tuberculosis (TB) and undernutrition: TB often causes undernutrition, and undernourished people are more likely to contract TB and experience worse outcomes. Globally, several TB nutritional support programmes exist; however, evidence on their effectiveness is limited and contested. This study evaluates the effect of a nutritional support programme implemented for people with TB in the Atsimo-Andrefana region, Madagascar in 2022. Within this programme, undernourished people with TB [with a body mass index (BMI) of < 18.5 kg/m2] receive 0.6 L of vegetable oil and 6.0 kg of a soy-wheat blend per month throughout their TB treatment.

Methods
We analysed secondary non-governmental organisation data collected between January and November 2022 in the Atsimo-Andrefana region, Southern Madagascar, including information on an individual’s medical conditions (e.g., type of TB, treatment outcomes) and nutritional status measured prior to, during, and after completion of treatment (e.g., height, weight, mid-upper arm circumference). We conducted descriptive analyses of patient baseline characteristics and outcomes to assess the impact of the provided nutritional support on the BMI of people with TB.

Results
A total of 1310 people with TB were included in the study [9.9% (130) children under the age of 5, 32.1% (420) children between 5 and 18 years, 58.0% (760) adults]. 55.4% of children under 5, 28.1% of children between ages 5 and 18, and 81.3% of adults were undernourished at treatment initiation. 42.3% (55/130) of children under 5 experienced severe acute malnutrition at treatment uptake. While the average BMI of adults with TB receiving food support increased over time, from 17.1 kg/m2 (interquartile range: 15.8–18.3, range: 10.3–22.5) to 17.9 kg/m2 (interquartile range: 16.6–19.1, range: 11.9–24.1), most adults remained undernourished even after completing TB treatment.

Conclusions
The current TB nutritional support programme falls short of sufficiently increasing the BMI of people with TB to overcome malnutrition. There is an urgent need to revise the nutritional support available for people with TB, particularly for children under 5.

Graphical Abstract