bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of soft tissue asymmetry indicators to characterize aging and functional mobility
Authors: Ricciardi Carlo , Ponsiglione Alfonso Maria , Recenti Marco , Amato Francesco , Gislason Magnus Kjartan , Chang Milan , Gargiulo Paolo 
Published: December 2023

Introduction: The aging population poses significant challenges to healthcare systems globally, necessitating a comprehensive understanding of age-related changes affecting physical function. Age-related functional decline highlights the urgency of understanding how tissue composition changes impact mobility, independence, and quality of life in older adults. Previous research has emphasized the influence of muscle quality, but the role of tissue composition asymmetry across various tissue types remains understudied. This work develops asymmetry indicators based on muscle, connective and fat tissue extracted from cross-sectional CT scans, and shows their interplay with BMI and lower extremity function among community-dwelling older adults.Methods: We used data from 3157 older adults from 71 to 98 years of age (mean: 80.06). Tissue composition asymmetry was defined by the differences between the right and left sides using CT scans and the non-Linear Trimodal Regression Analysis (NTRA) parameters. Functional mobility was measured through a 6-meter gait (Normal-GAIT and Fast-GAIT) and the Timed Up and Go (TUG) performance test. Statistical analysis included paired t-tests, polynomial fitting curves, and regression analysis to uncover relationships between tissue asymmetry, age, and functional mobility.Results: Findings revealed an increase in tissue composition asymmetry with age. Notably, muscle and connective tissue width asymmetry showed significant variation across age groups. BMI classifications and gait tasks also influenced tissue asymmetry. The Fast-GAIT task demonstrated a substantial separation in tissue asymmetry between normal and slow groups, whereas the Normal-GAIT and the TUG task did not exhibit such distinction. Muscle quality, as reflected by asymmetry indicators, appears crucial in understanding age-related changes in muscle function, while fat and connective tissue play roles in body composition and mobility.Discussion: Our study emphasizes the importance of tissue asymmetry indicators in understanding how muscle function changes with age in older individuals, demonstrating their role as risk factor and their potential employment in clinical assessment. We also identified the influence of fat and connective tissue on body composition and functional mobility. Incorporating the NTRA technology into clinical evaluations could enable personalized interventions for older adults, promoting healthier aging and maintaining physical function.
Three-dimensional hydrogel with human Wharton jelly-derived mesenchymal stem cells towards nucleus pulposus niche
Authors: Mohd Isa Isma Liza , Zulkiflee Izzat , Ogaili Raed H. , Mohd Yusoff Nurul Huda , Sahruddin Natasya Nadia , Sapri Shaiful Ridzwan , Mohd Ramli Elvy Suhana , Fauzi Mh Busra , Mokhtar Sabarul Afian 
Published: December 2023

Introduction: A regenerative strategy employing extracellular matrix (ECM)-based biomaterials and stem cells provide a better approach to mimicking the three-dimensional (3D) microenvironment of intervertebral disc for endogenous tissue regeneration. However, there is currently limited understanding regarding the human Wharton Jelly derived-mesenchymal stem cells (hWJ-MSCs) towards nucleus pulposus (NP)-like cells. Our study focused on the development of 3D bioengineered hydrogel based on the predominant ECM of native NP, including type II collagen (COLII) and hyaluronic acid (HA), which aims to tailor the needs of the microenvironment in NP.Methods: We have fabricated a 3D hydrogel using from COLII enriched with HA by varying the biomacromolecule concentration and characterised it for degradation, stability and swelling properties. The WJ-MSC was then encapsulated in the hydrogel system to guide the cell differentiation into NP-like cells.Results: We successfully fabricated COLII hydrogel (2 mg/ml) and HA 10 mg/ml at a weight ratio of HA and COLII at 1:9 and 4.5:9, and both hydrogels physically maintained their 3D sphere-shaped structure after complete gelation. The higher composition of HA in the hydrogel system indicated a higher water intake capacity in the hydrogel with a higher amount of HA. All hydrogels showed over 60% hydrolytic stability over a month. The hydrogel showed an increase in degradation on day 14. The hWJ-MSCs encapsulated in hydrogel showed a round morphology shape that was homogenously distributed within the hydrogel of both groups. The viability study indicated a higher cell growth of hWJ-MSCs encapsulated in all hydrogel groups until day 14.Discussion: Overall, our findings demonstrate that HA/COLII hydrogel provides an optimal swelling capacity, stability, degradability, and non-cytotoxic, thus mimics the NP microenvironment in guiding hWJ-MSCs towards NP phenotype, which is potentially used as an advanced cell delivery system for intervertebral disc regeneration.
Brewers’ spent grain pretreatment optimisation to enhance enzymatic hydrolysis of whole slurry and resuspended pellet
Authors: Castilla-Archilla Juan , Cermeño Maria , Tuohy Maria G. , FitzGerald Richard J. , Lens Piet N. L. 
Published: December 2023

A thermal diluted acid pretreatment using brewers spent grain (BSG) was optimised to improve enzymatic hydrolysis while minimising energy and chemical inputs. First, the use of hydrochloric or sulfuric acid for pretreatment was compared, using hydrochloric acid for the next steps. Three different dilute acid thermal pretreatment combinations were optimised in terms of acid concentration, temperature and time using a response surface methodology. Optimization was based on i) highest remaining protein content in the solid fraction (C1: 0.49% HCl; 87.7°C; 92 min), ii) highest liquid recovery (C2: 0.80% HCl; 121.0°C; 142 min), iii) lowest acid concentration applied to achieve largest protein and lowest remaining solid levels (C3: 0.10% HCl; 104.0°C; 70 min); and iv) a final condition based on the lowest water retention capacity when using HCl (C4: 0.20% HCl; 121.0°C; 20 min). The efficiency of enzymatic hydrolysis was evaluated, in the absence and presence of a large concentration of reducing carbohydrates, by centrifuging the slurry after acid pretreatment, recovering the solid fraction and resuspending it in fresh water. In C2, the enzyme (Depol 40L) was added directly to the entire slurry after pretreatment. For C1, C3, and C4 direct addition of enzyme to the whole slurry resulted in a higher release of carbohydrates during hydrolysis. Only in the case of C2 did the use of the resuspended solid result in a higher carbohydrate release. The overall carbohydrate recovery efficiency in the liquid fractions for C1, C2, C3 and C4 corresponded to 399.1 (±26.1), 535.8 (±28.7), 257.0 (±11.5), and 446.3 (±81.1) mg carbohydrate per Gram of BSG (dry weight), respectively. C1 and C4 were considered the optimal pretreatments as these combined a low acid concentration and energy input prior to enzymatic hydrolysis.
Effect of blood pressure on mortality in patients with cognitive impairment: a prospective cohort study
Authors: Shang YanChang , Wang ShuHui , Wei Chao , Gao ZhongBao , Xie HengGe , Wang ZhenFu 
Published: December 2023

BackgroundCognitive impairment is a prevalent condition that substantially elevates mortality rates among the elderly. The impact of hypertension on mortality in older adults with cognitive impairment is a subject of contention. This study aims to examine the influence of hypertension on both all-cause and CVD-specific mortality in elderly individuals experiencing cognitive impairment within a prospective cohort.MethodsThis study encompassed 2,925 participants (weighted 53,086,905) aged 60 years or older from National Health and Nutrition Examination Survey (NHANES) spanning 2011–2014. Incidence of all-cause and CVD-specific mortality was ascertained through linkage with National Death Index records until 31 December 2019. Survival was performed employing the Kaplan–Meier method. Hazard ratios (HRs) were calculated via Cox proportional hazards regression models.ResultsOver the follow-up period of up to 9.17 years [with a median (IQR) time to death of 6.58 years], equivalent to 18,731.56 (weighted 3.46 × 108) person-years, there were a total of 576 recorded deaths. Participants with CI exhibited a 1.96-fold higher risk of all-cause mortality (95% CI: 1.55–2.49; p &lt; 0.01) and a 2.8-fold higher risk of CVD-specific mortality (95% CI: 1.83–4.29; p &lt; 0.01) in comparison to participants without CI. Among participants with CI, concurrent hypertension comorbidity was linked to a 2.73-fold elevated risk of all-cause mortality (95% CI: 1.78–4.17; p &lt; 0.01) and a 5.3-fold elevated risk of CVD-specific mortality (95% CI: 2.54–11.04; p &lt; 0.01). Further stratified analyses revealed that the combined effects of hypertension and CI on all-cause and CVD-specific mortality were more pronounced in participants aged 60–69 years compared to those aged 70–80 years (p for interaction &lt;0.01). The primary findings exhibited resilience across a series of sensitivity analyses.ConclusionsParticipants with CI exhibited a markedly elevated risk of all-cause and CVD-specific mortality when coexisting with hypertension. Appropriate management of hypertension in patients with CI may be helpful in reducing the excess risk of death.
The determinants of postpartum contraceptive use in Nigeria
Authors: Anyatonwu Obinna Princewill , Nwoku Kelechi Amy , Jonsson Håkan , Namatovu Fredinah 
Published: December 2023

IntroductionPostpartum contraception is vital for maternal and child health, and reduces the risk of infant mortality. The Health Belief Model (HBM) is a widely accepted framework for exploring health behaviors, such as contraceptive use. Therefore, this study aimed to investigate the factors influencing postpartum contraceptive use in Nigeria and to contextualize the findings within the framework of the HBM.MethodsThis study was a secondary analysis of cross-sectional data collected from the Demographic Health Survey conducted in Nigeria (NDHS). In total, 28,041 women were included in this study. Self-reported contraceptive use was the outcome, while the explanatory variables included maternal age, place of residence, region of residence, religion, marital status, educational level, household wealth quintiles, knowledge of the ovulatory cycle, decision-maker for health care, and distance to health care facilities. Descriptive statistics and multivariate logistic regression were used to summarize and identify factors influencing postpartum contraceptive use. The HBM was used to discuss the main findings.ResultsThe prevalence of postpartum contraceptive use in Nigeria is 27%. Our findings showed that the odds of using contraceptives during the postpartum period were higher among women who knew their ovulation cycles, lived in urban areas in the southern region, had no distance barriers to health care, and were 25–49 years old. Education, wealth, and marital status also increase the odds of contraceptive use. However, women who lived in the northeast and northwest regions or shared decision-making with their partners had lower odds.ConclusionThis study highlights the need for region-specific and age-focused interventions to increase contraceptive use in Nigeria. Additionally, increasing accessibility and affordability of contraceptives for younger and economically disadvantaged women, along with promoting women's autonomy in decision-making, can further enhance contraceptive use across Nigeria.
Clinical characteristics and prognosis in patients with neuronal surface antibody-mediated autoimmune encephalitis: a single-center cohort study in China
Authors: Huang Teng , Liu Fei , Wang Baojie , Wang Chunjuan , Hao Maolin , Guo Shougang 
Published: December 2023

ObjectiveThis retrospective observational study primarily aimed to analyse the clinical characteristics of patients with neuronal surface antibody-mediated autoimmune encephalitis (AE) in China and report their prognosis after immunotherapy.MethodsClinical characteristics, laboratory or imaging examinations, and treatment outcomes of 103 patients diagnosed with AE between 1 September 2014 and 31 December 2020 were collected. Univariate and multivariate logistic regression analyses were performed to determine the predictors of poor prognosis.ResultsOverall, 103 patients were enrolled in the study. The main clinical symptoms included seizures (74.8%), psychiatric and behavior disorders (66.0%), cognitive deficits (51.5%), disturbances of consciousness (45.6%), and movement disorders/involuntary movements (26.2%). The distribution of clinical syndromes also differed for different AE subtypes. The efficacy rates of first-line immunotherapy for anti-NMDAR, anti-LGI1, anti-GABABR, and anti-CASPR2 encephalitis were 70.2%, 92.3%, 70%, and 83.3%, respectively, and rituximab was administered to 21 patients as second-line immunotherapy, including 14 patients with anti-NMDAR encephalitis, 4 with anti-LGI1 encephalitis, 2 with anti-GABABR encephalitis, and 1 with anti-CASPR2 encephalitis. Five patients with poor effect of the second-line treatment received bortezomib. According to the results of the last follow-up, 78 patients had a good prognosis (mRS 0–2), and 21 patients had a poor prognosis (mRS 3–6). The proportion of patients with a poor prognosis was significantly higher in anti-GABABR encephalitis compared to the other AE subtypes (p&lt;0.001). Multivariate analysis indicated that elevated neutrophil-to-lymphocyte ratio (NLR) and tumour presence were independent risk factors for poor prognosis. The regression equation of the model was logit(P)=-3.480 + 0.318 NLR+2.434 with or without tumour (with assignment =1, without assignment =0). The prediction probability generated by the regression model equation was used as the independent variable for receiver operating curve (ROC) analysis. The results showed that the area under the curve (AUC) of the prediction probability was 0.847 (95% CI, 0.733–0.961; p &lt; 0.001).ConclusionsDifferent AE subtypes demonstrated different clinical symptom spectra throughout the disease stage. Anti-LGI1 encephalitis and anti-CASPR2 encephalitis were more sensitive to first-line and second-line treatments. Anti-GABABR encephalitis had the worst prognosis among the abovementioned subtypes. The regression equation constructed using NLR and tumour presence effectively predicted the poor prognosis.
A highly potent anti-VISTA antibody KVA12123 - a new immune checkpoint inhibitor and a promising therapy against poorly immunogenic tumors
Authors: Iadonato Shawn , Ovechkina Yulia , Lustig Kurt , Cross Jessica , Eyde Nathan , Frazier Emily , Kabi Neda , Katz Chen , Lance Remington , Peckham David , Sridhar Shaarwari , Talbaux Carla , Tihista Isabelle , Xu Mei , Guillaudeux Thierry 
Published: December 2023

BackgroundImmune checkpoint therapies have led to significant breakthroughs in cancer patient treatment in recent years. However, their efficiency is variable, and resistance to immunotherapies is common. VISTA is an immune-suppressive checkpoint inhibitor of T cell response belonging to the B7 family and a promising novel therapeutic target. VISTA is expressed in the immuno-suppressive tumor microenvironment, primarily by myeloid lineage cells, and its genetic knockout or antibody blockade restores an efficient antitumor immune response.MethodsFully human monoclonal antibodies directed against VISTA were produced after immunizing humanized Trianni mice and sorting and sequencing natively-linked B cell scFv repertoires. Anti-VISTA antibodies were evaluated for specificity, cross-reactivity, monocyte and T cell activation, Fc-effector functions, and antitumor efficacy using in vitro and in vivo models to select the KVA12123 antibody lead candidate. The pharmacokinetics and safety profiles of KVA12123 were evaluated in cynomolgus monkeys.ResultsHere, we report the development of a clinical candidate anti-VISTA monoclonal antibody, KVA12123. KVA12123 showed high affinity binding to VISTA through a unique epitope distinct from other clinical-stage anti-VISTA monoclonal antibodies. This clinical candidate demonstrated high specificity against VISTA with no cross-reactivity detected against other members of the B7 family. KVA12123 blocked VISTA binding to its binding partners. KVA12123 induced T cell activation and demonstrated NK-mediated monocyte activation. KVA12123 treatment mediated strong single-agent antitumor activity in several syngeneic tumor models and showed enhanced efficacy in combination with anti-PD-1 treatment. This clinical candidate was engineered to improve its pharmacokinetic characteristics and reduce Fc-effector functions. It was well-tolerated in preclinical toxicology studies in cynomolgus monkeys, where hematology, clinical chemistry evaluations, and clinical observations revealed no indicators of toxicity. No cytokines associated with cytokine release syndrome were elevated.ConclusionThese results establish that KVA12123 is a promising drug candidate with a distinct but complementary mechanism of action of the first generation of immune checkpoint inhibitors. This antibody is currently evaluated alone and in combination with pembrolizumab in a Phase 1/2 open-label clinical trial in patients with advanced solid tumors.
Case report: Whole-exome sequencing for a hereditary elliptocytosis case with an unexpectedly low HbA1c
Authors: Pang Lu , Zeng Ziyi , Ding Yadi , Huang Haiming , Li Haixia 
Published: December 2023

ObjectivesHereditary elliptocytosis is a group of erythroid hereditary diseases characterized by elliptically shaped erythrocytes in peripheral blood. It is mainly inherited through autosomal dominant inheritance. This study aimed to conduct a genetic etiology analysis in a case with a clinical diagnosis of hereditary elliptocytosis and an unexpectedly low HbA1c.MethodsWhole-exome sequencing was performed to find the possible pathogenic mutations. At the same time, bioinformatics software was used to predict the mutation function. Sanger sequencing was performed to verify the suspected pathogenic mutations.ResultsWhole-exome sequencing results showed that the proband with mild anemia had a heterozygous c.2303G&gt;A (p.G768D) missense mutation in the 13th exon of the SPTB gene. The Sanger sequencing confirmed this heterozygous mutation. This mutation was extremely rare in the population, and multiple software’s predictions were harmful. Conservative analysis revealed that this site was highly conserved in various species.ConclusionThe c.2303G&gt;A mutation of the SPTB gene is the suspected cause of hereditary elliptocytosis in the patient. Our data show that microscopic examination of red blood cells on blood smears is an important means of diagnosing hereditary elliptocytosis. Whole-exome sequencing is an effective tool to determine the genetic etiology of erythrocyte membrane diseases, which can promote accurate diagnosis and genetic counseling.
Late-onset cobalamin C deficiency type in adult with cognitive and behavioral disturbances and significant cortical atrophy and cerebellar damage in the MRI: a case report
Authors: Sun Miao , Dai Yingjie 
Published: December 2023

BackgroundLate-onset cobalamin C (cblC) deficiency is associated with a wide range of neurological and psychiatric symptoms, hematological manifestations, anorexia, renal failure, ocular abnormalities, dermatitis, and pancreatitis. However, the neuroimaging characteristics of late-onset cblC deficiency remain insufficiently documented. Common findings include diffuse white matter swelling, varying degrees of severe leukoaraiosis, hydrocephalus, corpus callosum atrophy, and symmetric bilateral basal ganglia lesions. In this report, we present a case of late-onset cblC deficiency in adults presenting with cerebellar ataxia as the primary symptom. The MRI findings revealed bilateral lateral cerebellar hemispheres exhibiting symmetric hyperintensity, primarily observed in diffusion-weighted imaging (DWI), which is a rarely reported imaging change in this context.Case presentationOur patient was a male who experienced symptoms starting at the age of 30 years, including unsteady walking, apparent cerebellar ataxia, and cognitive impairment upon nervous system examination. Brain magnetic resonance imaging (MRI) exhibited symmetric hyperintensity in the bilateral lateral cerebellar hemispheres, predominantly manifested in DWI, without any enhancement. Subsequently, significantly elevated blood total homocysteine and urinary methylmalonic acid levels were observed. Genetic analysis confirmed the presence of MMACHC compound heterozygous mutants c.482G &gt; A and c.609G &gt; A, thus confirming the diagnosis of cblC deficiency. These variants were classified as likely pathogenic following the guidelines of the American College of Medical Genetics and Genomics (ACMG) and were verified using Sanger sequencing. Following treatment, the patient experienced improvements in walking ability and cognition, a significant decrease in blood total homocysteine levels, and reversal of the imaging lesions.In conclusionLate-onset cblC deficiency presents with diverse clinical and imaging manifestations. Early diagnosis and treatment are crucial in achieving a favorable prognosis. This case serves as a reminder to clinicians not to overlook genetic metabolic disorders, particularly those causing multisite damage, in adult patients with undiagnosed neurological disorders, especially those affecting the cerebellum. Notably, methylmalonic acidemia should be considered within the spectrum of bilateral cerebellar lesions.
Trends in the incidence of peripheral vestibular disorders: a Nationwide population-based study
Authors: Hung Shih-Han , Xirasagar Sudha , Dang Luong Huu , Chen Yen-Chun , Cheng Yen-Fu , Lin Herng-Ching , Chen Chin-Shyan 
Published: December 2023

PurposeThis study aimed to examines the long-term trend of incidence of peripheral vestibular disorders between 2010 and 2018 in Taiwan.MethodsStudy-eligible patients were identified from Taiwan’s Longitudinal Health Insurance Database 2005 maintained by the Ministry of Health and Welfare in Taiwan. We retrieved 230,566 patients with a first-time diagnosis of peripheral vestibular disorders between 2010 and 2018. We calculated annual incidence rates of peripheral vestibular disorders per 100,000 population. We used the annual percent change (APC) to test the trend of peripheral vestibular disorders over time.ResultsThe mean annual incidence rate of peripheral vestibular disorders during the study period was 1489.6 per 100,000 population. Incidence showed a statistically significant steady decrease from 2010 to 2018 with a mean APC of −6.15% (95% CI = −6.97% ~ −5.32%). The decline was led by Meniere’s disease (APC = −9.83, 95% CI = −10.66% ~ −8.99%), followed by benign paroxysmal positional vertigo (APC = −3.69, 95% CI = −4.53% ~ −3.03%), vestibular neuritis (APC = −7.85, 95% CI = -8.96 ~ −6.73), and other peripheral vestibular dizziness (APC = −5.56, 95% CI = −6.69% ~ −4.43%).ConclusionThe incidence of peripheral vestibular disorders, overall, and the four major subgroups, benign paroxysmal positional vertigo, Meniere’s disease, vestibular neuritis, and other peripheral vestibular dizziness, all decreased substantially, year by year within the 2010–2018 period.