bluuebunny/crossref_metadata_2025_split huggingface dataset:
PKCε activator protects hippocampal microvascular disruption and memory defect in 3×Tg-Alzheimer’s disease mice with cerebral microinfarcts
Authors: Wang Huaixing , Zhang Zongxiu , Hongpaisan Jarin 
Published: December 2023

BackgroundCurrent evidence suggests that microvessel disease is involved in Alzheimer’s disease (AD). Cerebrovascular disease correlates with cardiovascular disease and is complicated in ≈40% of AD patients. The protein kinase C (PKC) ε activator DCPLA can stimulate human antigen (Hu) R that prevents degradation and promotes the translation of mitochondrial Mn-superoxide dismutase (MnSOD) and vascular endothelial growth factor-A (VEGF) mRNAs.MethodsTo induce brain microinfarcts, we injected triple transgenic (3×Tg) and wild-type (WT) control mice with microbeads (20 μm caliber) into common carotid arteries, with or without the DCPLA-ME (methyl-ester) for 2 weeks. After water maze training, mice at 16 months old were examined for confocal immunohistochemistry at a single cell or microvessel level in the hippocampal CA1 area, important for spatial memory storage, and in the dorsal hippocampus by western blots.ResultsIn 3×Tg mice without cerebral microinfarcts, an accelerating age-related increase in (mild) oxidative stress and hypoxia inducible factor (HIF)-1α, but a reduction in VEGF, mitochondrial transcription factor A (TFAM), and MnSOD were associated with capillary loss. The change was less pronounced in arterioles. However, in 3×Tg mice with cerebral microinfarcts, increasing arteriolar diameter and their wall cells were related with the strong oxidative DNA damage 8-hydroxy-2′-deoxyguanosine (8-OHdG), apoptosis (cleaved caspase 3), and sustained hypoxia (increased HIF-1α and VEGF/PKCε/extracellular signal regulated kinase or ERK pathway). Microocclusion enhanced the loss of the synaptic marker spinophilin, astrocytic number, and astrocyte-vascular coupling areas and demyelination of axons. DCPLA-ME prevented spatial memory defect; strong oxidative stress-related apoptosis; sustained hypoxia (by reducing HIF-1α and VEGF); and exaggerated cell repair in arteriolar walls, pericapillary space dilation, neuro-glial-vascular disruption, and demyelination.ConclusionIn conclusion, in 3×Tg mice with cerebral microinfarcts, sustained hypoxia (increased HIF-1α and VEGF signals) is dominant with arteriolar wall thickening, and DCPLA has a protective effect on sustained hypoxia.
Complications and outcomes of hospitalizations for patients with and without Parkinson disease
Authors: George Benjamin P. , Barbosa William A. , Sethi Anish , Richard Irene H. 
Published: December 2023

ObjectiveTo examine complications and outcomes of hospitalizations for common indications for hospitalization among patients with Parkinson disease (PD).MethodsWe identified and selected the ten most common indications for hospitalization among individuals ≥65 years of age using principal diagnoses from the California State Inpatient Database, 2018–2020. Patients with comorbid PD were identified using secondary diagnosis codes and matched one-to-one to patients without PD based on principal diagnosis (exact matching), age, gender, race and ethnicity, and Elixhauser comorbidity index (coarsened exact matching). We identified potentially preventable complications based on the absence of present on admission indicators among secondary diagnoses. In the matched cohort, we compared inpatient complications, early Do-Not-Resuscitate (DNR) orders (placed within 24 h of admission), use of life-sustaining therapies, new nursing facility requirement on discharge, and death or hospice discharge for patients with and without PD.ResultsWe identified 35,457 patients with PD among the ten leading indications for hospitalization in older adults who were matched one-to-one to patients without PD (n = 70,914 in total). Comorbid PD was associated with an increased odds of developing aspiration pneumonia (OR 1.17 95% CI 1.02–1.35) and delirium (OR 1.11 95% CI 1.02–1.22) during admission. Patients with PD had greater odds of early DNR orders [placed within 24 h of admission] (OR 1.34 95% CI 1.29–1.39). While there was no difference in the odds of mechanical ventilation (OR 1.04 95% CI 0.98–1.11), patients with PD demonstrated greater odds of tracheostomy (OR 1.41 95% CI 1.12–1.77) and gastrostomy placement (OR 2.00 95% CI 1.82–2.20). PD was associated with greater odds of new nursing facility requirement upon discharge (OR 1.58 95% CI 1.53–1.64). Patients with PD were more likely to die as a result of their hospitalization (OR 1.11 95% CI 1.06–1.16).ConclusionPatients with PD are at greater risk of developing aspiration pneumonia and delirium as a complication of their hospitalization. While patients with PD more often have early DNR orders, they have greater utilization of life-sustaining therapies and experience worse outcomes of their hospitalization including new nursing facility requirement upon discharge and greater mortality.
Neuromyelitis optica spectrum disorder safely and successfully treated with satralizumab during pregnancy and breastfeeding: a case report
Authors: Yoshida Takashi , Watanabe Osamu , Nomura Miwa , Yoshimoto Yusuke , Maki Yoshimitsu , Takashima Hiroshi 
Published: December 2023

BackgroundSatralizumab, a monoclonal antibody that recognizes interleukin-6 receptors, is known to reduce the relapse rate in neuromyelitis optica spectrum disorder (NMOSD), but its safety during pregnancy has not been established. We present the case of an NMOSD patient who safely completed pregnancy, parturition, and breastfeeding under satralizumab treatment. Importantly, satralizumab transfer to umbilical cord blood, infant serum, or breast milk was not observed.Case presentationA 37-year-old Japanese female developed anti-aquaporin 4 antibody-positive NMOSD with left optic neuritis. Despite responding to steroid and azathioprine therapy, she experienced moon face and weight gain and desired the prompt reduction of the steroid dosage. She also wanted to conceive a child with a safe and preferably early pregnancy and parturition. Because pregnancy and parturition after the onset of NMOSD elevate the risk of relapse and miscarriage, treatment with satralizumab was initiated with the patient's consent. She experienced normal parturition and continued with satralizumab, steroid, and azathioprine treatments while breastfeeding without experiencing any relapses. Concentrations of satralizumab in the umbilical cord blood, infant serum, and breast milk were below the detection sensitivity.ConclusionThese findings suggest that satralizumab may be safe and effective for the perinatal management of NMOSD, especially when there are concerns about continuing pregnancy and the risk of relapse after parturition.
Urine-based point-of-care testing for factor-Xa-inhibitors in acute ischemic stroke patients: a feasibility study
Authors: Doeppner Thorsten R. , Olbricht Linus , Maxhuni Toska , Alhaj Omar Omar , Sachs Ulrich J. , Juenemann Martin B. , Huttner Hagen B. , Gerner Stefan T. 
Published: December 2023

IntroductionDirect oral anticoagulants (DOACs) have become widely used in clinical practice for preventing thromboembolic events. Point-of-care testing methods, particularly those based on urine samples, offer a promising approach for rapid and accurate assessment of DOAC presence. This pilot study aims to evaluate the utility of a urine-based DOAC dipstick test as a point-of-care tool for identifying DOAB presence in acute ischemic stroke (AIS) or transient ischemic attack (TIA) patients.Patients and methodsThis prospective pilot study included patients with AIS/TIA eligible for DOAC-measurement. After exclusion of 3 patients, 23 patients with DOAC-intake (DOAC group; factor-Xa-inhibitors; n = 23) and 21 patients without DOAC-intake (control-group) remained for analyses. The urine-based DOAC dipstick test and parallel blood-based specific DOAC-level assessment were performed in all patients. Time-intervals of sampling urine/blood sampling and result of DOAC-test were recorded to analyze a potential time benefit based on dipstick evaluation.ResultsThe urine-based DOAC dipstick test demonstrated high sensitivity (100%) and specificity (100%), correctly identifying all patients with anticoagulatory activity due to DOAC intake (i.e., anti-Xalevel ≥30 ng/mL). Moreover, the visual readout of the test provided semiquantitative information on drug-specific anti-Xa levels, showing a sensitivity of 83% and specificity of 93% to detect anti-Xa levels ≥120 ng/mL. The dipstick test exhibited a median time-benefit of 2:25 h compared to standard blood-based DOAC-level testing.DiscussionThe results of this pilot study underline the efficacy of urine-based point-of-care testing as a rapid and reliable method for assessing DOAC presence in patients with acute ischemic stroke.ConclusionThe value of this tool for clinical decision-making in stroke management needs to be established in future trials.Clinical Trial Registration: Clinicaltrails.org identifier [NCT06037200].
Elucidating the Influence of MPT-driven necrosis-linked LncRNAs on immunotherapy outcomes, sensitivity to chemotherapy, and mechanisms of cell death in clear cell renal carcinoma
Authors: Huang Jinbang , Liu Mengtao , Chen Haiqing , Zhang Jinhao , Xie Xixi , Jiang Lai , Zhang Shengke , Jiang Chenglu , Zhang Jieying , Zhang Qinhong , Yang Guanhu , Chi Hao , Tian Gang 
Published: December 2023

BackgroundClear cell renal carcinoma (ccRCC) stands as the prevailing subtype among kidney cancers, making it one of the most prevalent malignancies characterized by significant mortality rates. Notably,mitochondrial permeability transition drives necrosis (MPT-Driven Necrosis) emerges as a form of cell death triggered by alterations in the intracellular microenvironment. MPT-Driven Necrosis, recognized as a distinctive type of programmed cell death. Despite the association of MPT-Driven Necrosis programmed-cell-death-related lncRNAs (MPTDNLs) with ccRCC, their precise functions within the tumor microenvironment and prognostic implications remain poorly understood. Therefore, this study aimed to develop a novel prognostic model that enhances prognostic predictions for ccRCC.MethodsEmploying both univariate Cox proportional hazards and Lasso regression methodologies, this investigation distinguished genes with differential expression that are intimately linked to prognosis.Furthermore, a comprehensive prognostic risk assessment model was established using multiple Cox proportional hazards regression. Additionally, a thorough evaluation was conducted to explore the associations between the characteristics of MPTDNLs and clinicopathological features, tumor microenvironment, and chemotherapy sensitivity, thereby providing insights into their interconnectedness.The model constructed based on the signatures of MPTDNLs was verified to exhibit excellent prediction performance by Cell Culture and Transient Transfection, Transwell and other experiments.ResultsBy analyzing relevant studies, we identified risk scores derived from MPTDNLs as an independent prognostic determinant for ccRCC, and subsequently we developed a Nomogram prediction model that combines clinical features and associated risk assessment. Finally, the application of experimental techniques such as qRT-PCR helped to compare the expression of MPTDNLs in healthy tissues and tumor samples, as well as their role in the proliferation and migration of renal clear cell carcinoma cells. It was found that there was a significant correlation between CDK6-AS1 and ccRCC results, and CDK6-AS1 plays a key role in the proliferation and migration of ccRCC cells. Impressive predictive results were generated using marker constructs based on these MPTDNLs.ConclusionsIn this research, we formulated a new prognostic framework for ccRCC, integrating mitochondrial permeability transition-induced necrosis. This model holds significant potential for enhancing prognostic predictions in ccRCC patients and establishing a foundation for optimizing therapeutic strategies.
Detection of lymph node metastasis in colon cancer by ectopically expressed fibroblast markers FOXQ1 and THBS2
Authors: Ali Haytham , AbdelMageed Manar , Olsson Lina , Lindmark Gudrun , Hammarström Marie-Louise , Hammarström Sten , Sitohy Basel 
Published: December 2023

IntroductionApproximately 25% of colon cancer (CC) patients having curative surgery will relapse. Therefore, it is crucial to identify patients with increased recurrence risk to offer them adjuvant chemotherapy. Three markers with prominent expression in fibroblasts: forkhead box Q1 (FOXQ1), matrix metalloproteinase-11 (MMP11), and thrombospondin-2 (THBS2), and the fibroblast expressed chemokine CXCL12 were selected for studies because of the critical role of fibroblasts in the microenvironment of the tumor.MethodsThe expression levels of the biomarkers were assessed in primary CC tumors, lymph nodes of CC patients and controls, and CC cell lines at mRNA and protein levels by real-time qRT-PCR and immunohistochemistry, respectively.ResultsFOXQ1, MMP11, and THBS2 mRNAs were expressed at significantly higher levels in primary tumors compared to normal colon (P=0.002, P&lt;0.0001, and P&lt;0.0001, respectively). In contrast, CXCL12 mRNA levels were higher in normal colon tissue. FOXQ1, MMP11, and THBS2 levels were also expressed at significantly higher levels in metastasis-positive lymph nodes compared to both metastasis-negative- and control nodes (P&lt;0.0001/P=0.002, P&lt;0.0001/P&lt;0.0001, and P&lt;0.0001/P&lt;0.0001, respectively). Immuno-morphometry revealed that 30–40% of the tumor cells expressed FOXQ1, MMP11, and THBS2. FOXQ1 and THBS2 were barely detected in normal colon epithelium (P&lt;0.0001), while MMP11 was expressed in normal colon epithelium at high levels.DiscussionWe conclude that CC tumor cells show ectopic expression of FOXQ1 and THBS2 possibly making these tumor cells independent of fibroblast cell support. The high expression levels of these two biomarkers in metastatic lymph nodes suggest that they are potential indicators of patients at risk for recurrence.
Lung cancer mortality and associated predictors: systematic review using 32 scientific research findings
Authors: Tesfaw Lijalem Melie , Dessie Zelalem G. , Mekonnen Fenta Haile 
Published: December 2023

BackgroundCancer is a chronic disease brought on by mutations to the genes that control our cells’ functions and become the most common cause of mortality and comorbidities. Thus, this study aimed to assess the comprehensive and common mortality-related risk factors of lung cancer using more than thirty scientific research papers.MethodsPossible risk factors contributing to lung cancer mortality were assessed across 201 studies sourced from electronic databases, including Google Scholar, Cochrane Library, Web of Science (WOS), EMBASE, Medline/PubMed, the Lung Cancer Open Research Dataset Challenge, and Scopus. Out of these, 32 studies meeting the eligibility criteria for meta-analysis were included. Due to the heterogeneous nature of the studies, a random-effects model was applied to estimate the pooled effects of covariates.ResultsThe overall prevalence of mortality rate was 10% with a 95% confidence interval of 6 and 16%. Twenty studies (62.50%) studies included in this study considered the ages of lung cancer patients as the risk factors for mortality. Whereas, eighteen (56.25%) and thirteen (40.63%) studies incorporated the gender and smoking status of patients respectively. The comorbidities of lung cancer mortality such as cardiovascular disease, hypertension, diabetes, and pneumonia were also involved in 7 (21.90%), 6 (18.75%), 5 (15.63%), and 2 (6.25%) studies, respectively. Patients of older age are more likely to die as compared to patients of younger age. Similarly, lung patients who had smoking practice were more likely to die as compared to patients who hadn’t practiced smokingConclusionThe mortality rate of lung cancer patients is considerably high. Older age, gender, stage, and comorbidities such as cardiovascular, hypertension, and diabetes have a significant positive effect on lung cancer mortality. The study results will contribute to future research, management, and prevention strategies for lung cancer.
Physical fitness and motor competence performance characteristics of Chinese elite youth athletes from four track and field throwing disciplines—a cross-sectional study
Authors: Zhao Kewei , Siener Maximilian , Zhao Yifan , Hohmann Andreas 
Published: December 2023

Purpose: For systematic athletic training and targeted talent development, it is essential to know the physical fitness and motor competencies of top athletes in detail. However, it can be difficult to identify differences in performance requirements and thus to provide adequate support, especially for sports that at first glance appear to have similar demands—such as track and field throwing disciplines. Therefore, the aim of the study was to examine the physical fitness and motor competence of top athletes from different throwing disciplines and to check whether the athletes’ performance parameters match the specific requirements of the respective sport.Methods: The study involved 289 male youth athletes (aged 14–18 years) across four distinct throwing disciplines: shot put (n = 101), hammer throw (n = 16), discus throw (n = 63), and javelin throw (n = 109). The performance evaluation comprised three anthropometric measurements and twelve motor performance prerequisites applicable to the throwing disciplines. Discriminant analysis and neural networks (Multilayer Perceptron) were implemented to determine the possibility of distinguishing among athletes from the four sports.Results: The study’s findings indicate that in male throwing athletes, disparities in general physical fitness and motor proficiency assessments discern the majority of talented young athletes based on their specific sport (discriminant analysis: 68.2%; multilayer perceptron analysis: 72.2%). This remains applicable irrespective of the classification method employed. Discus throwers possessed a height advantage, while shot putters and hammer throwers exhibited superior arm strength. Javelin throwers displayed better explosive strength and sprinting speed. Except for the hammer throwers, all events demonstrated a high level of explosive power in the medicine ball forward or backward throw test, which was especially crucial for shot put and discus athletes.Conclusion: The significance of physical fitness and motor competence tests in identifying and transferring talented athletes in track and field throwing disciplines has been affirmed. Using linear and non-linear classification methods, most athletes could be assigned to their correct sport. However, this also shows that slightly different training and talent identification is required for each of these sports. Furthermore, non-linear analysis methods can provide useful support for the development processes in junior competitive sports.
Occupational characteristics and disability-free survival after retirement age: an exploratory analysis from the ASPREE study
Authors: Alif Sheikh M. , Benke Geza P. , Ronaldson Kathlyn J. , Walker-Bone Karen , Woods Robyn L. , Tran Cammie , Beilin Lawrence J. , Tonkin Andrew M. , Owen Alice J. , McNeil John J. 
Published: December 2023

BackgroundCertain occupational characteristics have been linked with poor health and reduced longevity. However, the association between occupational characteristics and survival free of disability in a post-retirement age group has not been investigated.MethodsWe investigated outcomes in 12,215 healthy older Australian adults in the Aspirin in Reducing Events in the Elderly (ASPREE) and ASPREE Longitudinal Study of Older Persons (ALSOP) sub-study. The ISCO-88 major occupational groups, settings, and activity levels were assigned based on free-text job descriptions. The Finnish Job Exposure Matrix was used to assign occupational characteristics to the three longest-held jobs. The primary endpoint, disability-free survival, was defined as a composite measure of death, dementia, or persistent physical disability. The endpoint of all-cause mortality was analyzed separately. Because of multiple exploratory analyses, only those associations with a two-sided value of p less than 0.005 were considered statistically significant. Cox proportional hazard models were used to calculate adjusted hazard ratios.ResultsHaving worked in an ‘elementary’ occupation was associated with a reduction in disability-free survival. A specific impact on disability-free survival was observed among those whose work had involved high accident risk and adverse social climate. No significant relationship was identified with those previously exposed to sedentary work, vigorous physical activity, work primarily outdoors, or a range of other occupational characteristics. All-cause mortality was not increased among any of the occupational groups.ConclusionThis exploratory study found a reduction in disability-free survival among people who worked in ‘elementary’ occupations, with specific risks associated with occupations involving high accident risks and adverse social climate.
Depressive and anxiety symptoms during the COVID-19 pandemic in the oldest-old population and the role of psychosocial factors: a multivariate and multi-wave analysis
Authors: Gerhards Sina K. , Pabst Alexander , Luppa Melanie , Riedel-Heller Steffi G. 
Published: December 2023

BackgroundSince the oldest-old population was identified as a high-risk group for a severe course of the coronavirus disease and higher mortality, it was assumed that they might be particularly psychologically burdened. The aim of the study is to analyze the development of anxiety and depressive symptoms over the course of the pandemic from 2020 to 2022, as well as psychosocial factors associated with these outcomes.MethodWe analyzed data of n = 135 participants aged 78 to 97 years old (2020: M = 86.77, SD = 4.54) with three points of measurement from May to June 2020 (t1), March to May 2021 (t2) and November to January 2022 (t3). Besides sociodemographic variables, worries about the Sars-Cov-2 virus, living situation, perceived social support (ESSI), resilience (BRS), anxiety and depressive symptoms (BSI-18) were assessed. We calculated multilevel mixed-effects generalized linear models with a negative binominal distribution to model anxiety and depressive symptoms over time.ResultsWhile there is an increase in depressive and anxiety symptoms in the investigated oldest-old individuals in Germany from 2020 to 2021, there is no further increase in symptomatology from 2021 to 2022. Participants of older age reported higher levels of anxiety symptoms. Higher perceived social support was associated with both less depressive and less anxiety symptoms, while resilience was associated with less depressive symptoms only. More worries about the Sars-Cov-2 virus were associated with higher anxiety levels.ConclusionOverall, the oldest-old population appeared to show rather stable mental health after a slight increase in symptomatology within the first year of the pandemic. Social support is an important factor to target in mental health prevention programs for oldest-old individuals in times of future crises such as a pandemic.