bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of repair protocols and chewing simulation on the microtensile bond strength of two resin matrix ceramics to composite resin
Authors: Elkassaby Annan Ahmed , Kandil Mohamed M. , Alian Ghada Atef
Published: February 2024

Background

To assess the micro tensile bond strength (µTBS) of two resin matrix ceramic (RMC) blocks bonded to composite resin by using different repair protocols with and without chewing simulation (CS).

Materials and methods

Two resin matrix ceramic blocks (Vita Enamic and Lava Ultimate) were divided into 4 groups according to the surface treatments: Bur grinding (control), Bur grinding + silane, 9.5% HF acid etching, and 9.5% HF acid etching + silane. The single bond universal adhesive was applied on all specimens after the surface treatments according to the manufacturer’s instructions, it was administered actively on the treated surface for 20 s and then light cured for 10 s, followed by incremental packing of composite resin to the treated surface. Each group was further divided into 2 subgroups (with/without chewing simulation for 500,000 cycles). A micro tensile bond strength test was performed for each group (n = 15). The effect of surface treatments on the materials was examined by using a scanning electron microscope (SEM). The micro tensile bond strength (MPa) data were analyzed with a three-way ANOVA, the independent t-test, and one-way ANOVA followed by the Tukey post-hoc test.

Results

µTBS results were significantly higher for Lava Ultimate than Vita Enamic for all the surface treatment protocols with (p < 0.01). The chewing simulation significantly negatively affected the micro-tensile bond strength (p < 0.001). Bur grinding + saline exhibited the highest bond strength values for Lava Ultimate, both with and without chewing simulation. For Vita Enamic, bur grinding + saline and HF acid + saline showed significantly higher bond strength values compared to other surface treatments, both with and without chewing simulation (p ≤ 0.05).

Conclusion

Bur grinding + silane could be recommended as a durable repair protocol for indirect resin matrix ceramics blocks with composite resin material.
Effects of aquatic exercise program versus on-land exercise program on cancer-related fatigue, neuropathy, activity and participation, quality of life, and return to work for cancer patients: study protocol for a randomized controlled trial
Authors: Nissim Michal , Rottenberg Yakir , Karniel Naama , Ratzon Navah Z.
Published: February 2024

Background

Exercise has shown positive effects on fatigue, exhaustion, neuropathy, and quality of life in cancer patients. While on-land exercises have been studied, the aquatic environment offers unique advantages. Water's density and viscosity provide resistance, enhancing muscle strength, while hydrostatic pressure improves venous return. This trial aims to investigate the effect of aquatic exercises on time to return to work, work hours, work-related difficulties, daily life activity and participation, quality of life, exhaustion, fatigue, and neuropathy among cancer patients, compared to on-land exercise intervention group and a non-exercise group.

Methods

This randomized controlled trial will include 150 cancer patients aged 18–65 years with stage III colon cancer or breast cancer patients with lymph node involvement. Participants in the aquatic exercise intervention group will undergo an 8-week, twice-weekly group-based Ai-Chi program, while the on-land exercise group will perform identical exercise. The control group will not engage in any exercise.

The primary outcome will be assessed using an employment barriers questionnaire, capturing return to work date and working hours and daily life participation and activity and quality of life. Secondary outcomes include exhaustion, fatigue, and neuropathy. Data will be collected at baseline, post-intervention (8 weeks), and at 3,12, and 24 months. Mixed variance analyses will explore relationships among groups and over time for independent variables, with separate analyses for each dependent variable.

Discussion

The potential benefits include an earlier return to work for patients, reducing their need for social and economic support. The study's implications on socio-economic policies are noteworthy, as a successful intervention could offer a cost-effective and non-invasive solution, improving patients' quality of life and increasing their participation in daily activities. This, in turn, could lead to a faster return to work, contributing to both personal well-being and broader societal interests by reducing reliance on social services.

Trial registration

The trial is registered at ClinicalTrials.gov NCT05427344 (22 June 2022).
Variation of the essential oil components of Citrus aurantium leaves upon using different distillation techniques and evaluation of their antioxidant, antidiabetic, and neuroprotective effect against Alzheimer’s disease
Authors: Elhawary Esraa A. , Nilofar Nilofar , Zengin Gokhan , Eldahshan Omayma A.
Published: February 2024

Citrus fruit essential oil is considered one of the widely studied essential oils while its leaves attract less attention although being rich in nearly the same composition as the peel and flowers. The leaves of bitter orange or sour orange (Citrus aurantium L.) were extracted using three different techniques namely; hydrodistillation (HD), steam distillation (SD), and microwave-assisted distillation (MV) to compare their chemical composition. The three essential oil samples were analyzed through GC/FID and GC/MS analyses. The samples were tested in vitro using different antioxidant techniques (DPPH, ABTS, CUPRAC, FRAP, PBD, and MCA), neuroprotective enzyme inhibitory activities (acetylcholine and butyl choline enzymes), and antidiabetic activities (α-amylase and α-glucosidase). The results showed that thirty-five volatile ingredients were detected and quantified. Monoterpenes represented the most abundant class in the three essential oils followed by sesquiterpenes. C. aurantium essential oil carried potential antioxidant activity where SD exhibited the highest antioxidant activity, with values arranged in the following order: FRAP (200.43 mg TE/g), CUPRAC (138.69 mg TE/g), ABTS (129.49 mg TE/g), and DPPH (51.67 mg TE/g). SD essential oil also presented the most potent α-amylase (0.32) inhibition while the MV essential oil showed the highest α-glucosidase inhibition (2.73 mmol ACAE/g), followed by HD (2.53 mmol ACAE/g), and SD (2.46 mmol ACAE/g). The SD essential oil exhibited the highest BChE and AChE inhibitory activities (3.73 and 2.06 mg GALAE/g), respectively). Thus, bitter orange essential oil can act as a potential source of potent antioxidant, antidiabetic, and neuroprotective activities for future drug leads.
Nursing experience and leadership skills among staff nurses and intern nursing students in Saudi Arabia: a mixed methods study
Authors: Alilyyani Bayan , Althobaiti Emad , Al-Talhi Muath , Almalki Talal , Alharthy Tariq , Alnefaie Mohammed , Talbi Husam , Abuzaid Ahmed
Published: February 2024

Background

Nurse leaders have a crucial impact in healthcare settings. Hospitals require qualified nurses with leadership skills to provide healthy work environments and enhance the outcomes related to staff nurses and patients. This study aimed to investigate the effect of nursing experience on leadership skills among staff nurses and intern nursing students.

Methods

A mixed methods design was applied (quantitative survey design for quantitative part and open-ended questions for qualitative part). Convenience sampling of staff nurses and intern nursing students in Saudi Arabia was applied. There were148 participants who completed the survey of the quantitative part, and 50 of them completed the qualitative part. Participants completed the Leadership Practice Inventory Questionnaire. SPSS v26 was used to analyze quantitative part, and thematic analysis was used to analyze qualitative part.

Results

This study found a significance difference among participating groups regarding to the years of experience (F = 5.05, p = 0.00). Three themes were found for the qualitative part which were strategies to enhance leadership skills, factors affecting leadership skills, and obstacles facing participants related to leadership skills. The qualitative data also revealed that participants found that clinical supervision and education ways to enhance the leadership skills, while work pressure, work environment and communication were obstacles of developing their leadership skills.

Conclusion

Leadership skills are considered as a significant component of the function of qualified nurses and should be viewed as central to intern nursing students’ learning development. Moreover, leadership skills are essential for the patient and organization outcomes. Nursing colleges and educators play an important role in enhancing to leadership skills as well as experience. Nurse leaders can create healthy care environments that have high quality and safety for patients. Management systems in healthcare organizations must motivate and support clinical leaders who can recognize both individual and clinical requirements and address current issues in their field.
The impact of education/training on nurses caring for patients with stroke: a scoping review
Authors: Zhao Yanjie , Xu Yuezhen , Ma Dongfei , Fang Shuyan , Zhi Shengze , He Meng , Zhu Xiangning , Dong Yueyang , Song DongPo , Yiming Atigu , Sun Jiao
Published: February 2024

Background

Stroke survivors have complex needs that necessitate the expertise and skill of well-trained healthcare professionals to provide effective rehabilitation and long-term support. Limited knowledge exists regarding the availability of specialized education and training programs specifically designed for nurses caring for stroke patients.

Aim

This review aims to assess the content and methods of training for nurses caring for stroke patients, examine its impact on both nurses and patients, and identify key facilitators and barriers to its implementation.

Methods

We conducted a comprehensive scoping review by reviewing multiple databases, including PubMed, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, Embase, Web of Science, Scopus, ProQuest Dissertations and Theses, Google Scholar, and Cochrane databases. Data extraction and narrative synthesis were performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines.

Results

Seventeen articles were included in this review. We found that education/training not only enhanced patients' self-care abilities, nursing outcomes, and satisfaction, but also had a positive impact on the knowledge, skills, and practices of nurses. The obstacles to education/training included feasibility and cost-effectiveness, while the driving factors were management support and participation, professional education/training, and controlled environment creation.

Conclusions

This review highlights the crucial role of education/training in enhancing stroke care provided by nurses. Effective education/training integrates various educational methods and management support to overcome implementation barriers and optimize clinical practice benefits. These findings indicate the necessity of universal and consistent stroke education/training for nurses to further improve patient outcomes in stroke care.
Understanding the barriers and facilitators to implementing and sustaining Mobile Overdose Response Services from the perspective of Canadian key interest groups: a qualitative study
Authors: Seo Boogyung , Rider Nathan , Rioux William , Teare Adrian , Jones Stephanie , Taplay Pamela , Monty Ghosh S.
Published: February 2024

Introduction

Unregulated supply of fentanyl and adulterants continues to drive the overdose crisis. Mobile Overdose Response Services (MORS) are novel technologies that offer virtual supervised consumption to minimize the risk of fatal overdose for those who are unable to access other forms of harm reduction. However, as newly implemented services, they are also faced with numerous limitations. The aim of this study was to examine the facilitators and barriers to the adoption of MORS in Canada.

Methods

A total of 64 semi-structured interviews were conducted between November 2021 and April 2022. Participants consisted of people who use substances (PWUS), family members of PWUS, health care professionals, harm reduction workers, MORS operators, and members of the general public. Inductive thematic analysis was used to identify the major themes and subthemes.

Results

Respondents revealed that MORS facilitated a safe, anonymous, and nonjudgmental environment for PWUS to seek harm reduction and other necessary support. It also created a new sense of purpose for operators to positively contribute to the community. Further advertising and promotional efforts were deemed important to increase its awareness. However, barriers to MORS implementation included concerns regarding privacy/confidentiality, uncertainty of funding, and compassion fatigue among the operators.

Conclusion

Although MORS were generally viewed as a useful addition to the currently existing harm reduction services, it’s important to monitor and tackle these barriers by engaging the perspectives of key interest groups.
Repurposing of Zika virus live-attenuated vaccine (ZIKV-LAV) strains as oncolytic viruses targeting human glioblastoma multiforme cells
Authors: Victorio Carla Bianca Luena , Novera Wisna , Ganasarajah Arun , Ong Joanne , Thomas Melisyaa , Wu Jonas , Toh Hilary Si Yin , Sun Alfred Xuyang , Ooi Eng Eong , Chacko Ann-Marie
Published: February 2024

Glioblastoma multiforme (GBM) is the most common malignant primary brain cancer affecting the adult population. Median overall survival for GBM patients is poor (15 months), primarily due to high rates of tumour recurrence and the paucity of treatment options. Oncolytic virotherapy is a promising treatment alternative for GBM patients, where engineered viruses selectively infect and eradicate cancer cells by inducing cell lysis and eliciting robust anti-tumour immune response. In this study, we evaluated the oncolytic potency of live-attenuated vaccine strains of Zika virus (ZIKV-LAV) against human GBM cells in vitro. Our findings revealed that Axl and integrin αvβ5 function as cellular receptors mediating ZIKV-LAV infection in GBM cells. ZIKV-LAV strains productively infected and lysed human GBM cells but not primary endothelia and terminally differentiated neurons. Upon infection, ZIKV-LAV mediated GBM cell death via apoptosis and pyroptosis. This is the first in-depth molecular dissection of how oncolytic ZIKV infects and induces death in tumour cells.
Long-term impact of maternal obesity on the gliovascular unit and ephrin signaling in the hippocampus of adult offspring
Authors: Shiadeh Seyedeh Marziyeh Jabbari , Goretta Fanny , Svedin Pernilla , Jansson Thomas , Mallard Carina , Ardalan Maryam
Published: February 2024

Background

Children born to obese mothers are at increased risk of developing mood disorders and cognitive impairment. Experimental studies have reported structural changes in the brain such as the gliovascular unit as well as activation of neuroinflammatory cells as a part of neuroinflammation processing in aged offspring of obese mothers. However, the molecular mechanisms linking maternal obesity to poor neurodevelopmental outcomes are not well established. The ephrin system plays a major role in a variety of cellular processes including cell–cell interaction, synaptic plasticity, and long-term potentiation. Therefore, in this study we determined the impact of maternal obesity in pregnancy on cortical, hippocampal development, vasculature and ephrin-A3/EphA4-signaling, in the adult offspring in mice.

Methods

Maternal obesity was induced in mice by a high fat/high sugar Western type of diet (HF/HS). We collected brain tissue (prefrontal cortex and hippocampus) from 6-month-old offspring of obese and lean (control) dams. Hippocampal volume, cortical thickness, myelination of white matter, density of astrocytes and microglia in relation to their activity were analyzed using 3-D stereological quantification. mRNA expression of ephrin-A3, EphA4 and synaptic markers were measured by qPCR in the brain tissue. Moreover, expression of gap junction protein connexin-43, lipocalin-2, and vascular CD31/Aquaporin 4 were determined in the hippocampus by immunohistochemistry.

Results

Volume of hippocampus and cortical thickness were significantly smaller, and myelination impaired, while mRNA levels of hippocampal EphA4 and post-synaptic density (PSD) 95 were significantly lower in the hippocampus in the offspring of obese dams as compared to offspring of controls. Further analysis of the hippocampal gliovascular unit indicated higher coverage of capillaries by astrocytic end-feet, expression of connexin-43 and lipocalin-2 in endothelial cells in the offspring of obese dams. In addition, offspring of obese dams demonstrated activation of microglia together with higher density of cells, while astrocyte cell density was lower.

Conclusion

Maternal obesity affects brain size, impairs myelination, disrupts the hippocampal gliovascular unit and decreases the mRNA expression of EphA4 and PSD-95 in the hippocampus of adult offspring. These results indicate that the vasculature–glia cross-talk may be an important mediator of altered synaptic plasticity, which could be a link between maternal obesity and neurodevelopmental/neuropsychiatric disorders in the offspring.

Graphical Abstract
Inhibition of HOXD11 promotes cartilage degradation and induces osteoarthritis development
Authors: Hong Quan , Liu Zhong-Xun , Liang Hai-Feng , Wu De-Guang , Chen Yan , Yu Bo
Published: February 2024

The 5′-HOXD genes are important for chondrogenesis in vertebrates, but their roles in osteoarthritis (OA) are still ambiguous. In our study, 5′-HOXD genes involvement contributing to cartilage degradation and OA was investigated. In bioinformatics analysis of 5′-HOXD genes, we obtained the GSE169077 data set related to OA in the GEO and analyzed DEGs using the GEO2R tool attached to the GEO. Then, we screened the mRNA levels of 5′-HOXD genes by quantitative reverse transcriptase–polymerase chain reaction (qRT-PCR). We discovered that OA chondrocyte proliferation was inhibited, and apoptosis was increased. Moreover, it was discovered that SOX9 and COL2A1 were downregulated at mRNA and protein levels, while matrix metalloproteinases (MMPs) and a disintegrin-like and metalloproteinase with thrombospondin motifs (ADAMTSs) were upregulated. According to the results of differentially expressed genes (DEGs) and qRT-PCR, we evaluated the protein level of HOXD11 and found that the expression of HOXD11 was downregulated, reversed to MMPs and ADAMTSs but consistent with the cartilage-specific factors, SOX9 and COL2A1. In the lentivirus transfection experiments, HOXD11 overexpression reversed the effects in OA chondrocytes. In human OA articular cartilage, aberrant subchondral bone was formed in hematoxylin–eosin (H&E) and Safranin O and fast green (SOFG) staining results. Furthermore, according to immunohistochemistry findings, SOX9 and HOXD11 expression was inhibited. The results of this study established that HOXD11 was downregulated in OA cartilage and that overexpression of HOXD11 could prevent cartilage degradation in OA.
Kirschner Wire Prying and Leverage Technique: a new closed reduction method in treatment of pediatric “Irreducible Supracondylar Humerus Fractures”
Authors: Xiao Yuan , Clement Arthur , Kang Chi , Ren Bo , Liu Xin
Published: February 2024

Background

This study employs an innovative closed reduction approach to treat pediatric "Irreducible Supracondylar Humerus Fractures" with the goal of demonstrating its practical application compared to conventional methods.

Methods

This study sampled 146 surgically treated cases of "Irreducible Supracondylar Humerus Fractures" in our department. After applying inclusion and exclusion criteria, 120 children were selected and divided into two groups based on treatment methods. Group 1 underwent Closed Reduction and Percutaneous Pinning (CRPP), while Group 2 received treatment using the Kirschner Wire Prying and Leverage Technique alongside CRPP. The relevant data to the study were collected and assessed during the follow-up period.

Results

Results indicate that Group 2 demonstrated significantly shorter operative times and fewer instances of intraoperative fluoroscopy compared to Group 1. Furthermore, the percentage of cases requiring open reduction was notably higher in Group 1 than in Group 2. The analysis also identified age, BMI, time from injury to surgery, and the initial deviation of the distal fragment as independent risk factors associated with the failure of closed reduction.

The integration of CRPP with the Kirschner Wire Prying and Leverage Technique emerges as a safe and effective strategy for managing "Irreducible Supracondylar Humerus Fractures." This innovative approach not only reduces operative time and intraoperative fluoroscopy needs but also diminishes the reliance on open reduction without compromising safety.
One case of surgical treatment of coagulation factor XI deficiency complicated with esophageal cancer: a case report
Authors: Tian Yang , Zheng Zhaowei , Song Nannan , Wang Jun
Published: February 2024

Background

Coagulation factor XI deficiency is an autosomal recessive hereditary disease with a low incidence. It usually occurs after surgery or trauma; Esophageal cancer is a common malignant tumor of the digestive tract in China. But so far, surgery-based comprehensive treatment of esophageal cancer still dominates.

Case presentation

We report a case of an Asian patient with XI factor deficiency and lower esophageal squamous cell carcinoma who was admitted to our hospital recently. After active preoperative preparation, the operation was successfully performed, and there was no obvious abnormal bleeding during and after the operation.

Conclusions

Coagulation factor XI deficiency is a relatively rare disease, and patients with the disease will face a greater risk of bleeding during the perioperative period. The encouraging perioperative outcome enables us to have a deeper understanding of surgical treatment strategies for patients with Coagulation factor XI deficiency.
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

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

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

Ovarian 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

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

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

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

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

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

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

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
Immersive virtual reality and computer vision for heritage: visual evaluation and perception of the industrial heritage sites along the Yunnan–Vietnam railway (Yunnan section)
Authors: Wang Yingxue , Wang Shuoyi , Pan Yue , Li Chunhua , Chen Chunxu , Wang Jin
Published: February 2024

The visual composition and human perception are found to relate to the reuse and tourism of heritage railways. Previous studies have used either environmental audits and on-site interviews that have limitations in terms of cost, time, and measurement scale, or virtual perception base on two-dimension images but with gaps in interactivity, virtual immersion and field of view. This study developed an “objective + subjective” visual evaluation and perception framework integrating Computer Vision (CV) and Immersive Virtual Reality (IVR) to assess the visual quality of industrial heritage sites along the Yunnan-Vietnam Railway (Yunnan Section). The stepwise multiple linear regression models were carried out to investigate the relationship between objective evaluation and subjective perception. The results showed that 16 landscape elements of the heritage sites were successfully segmented. According to the visual perception score bands, the 120 industrial heritage sites were classified as 39 high-score sites, 66 medium-score sites, and 15 low-score sites. In general, although the sky and hard ground accounted for a higher proportion, they had little effect on the sum scores, while the vegetation, water, and buildings played a significant role in the perception of visual quality. The results can help researchers, planners, and government departments clarify the visual quality to scientifically specify bottom-up planning and management solutions for railway industrial heritage sites. Moreover, the simplicity, accuracy, and effectiveness of this framework make it suitable for large-scale visual evaluation of other railway industrial heritage sites and linear heritage sites.