bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prominent tauopathy and intracellular β-amyloid accumulation triggered by genetic deletion of cathepsin D: implications for Alzheimer disease pathogenesis
Authors: Terron Heather M. , Parikh Sagar J. , Abdul-Hay Samer O. , Sahara Tomoko , Kang Dongcheul , Dickson Dennis W. , Saftig Paul , LaFerla Frank M. , Lane Shelley , Leissring Malcolm A. 
Published: April 2024

Abstract
Background
Cathepsin D (CatD) is a lysosomal protease that degrades both the amyloid-β protein (Aβ) and the microtubule-associated protein, tau, which accumulate pathognomonically in Alzheimer disease (AD), but few studies have examined the role of CatD in the development of Aβ pathology and tauopathy in vivo.

Methods
CatD knockout (KO) mice were crossed to human amyloid precursor protein (hAPP) transgenic mice, and amyloid burden was quantified by ELISA and immunohistochemistry (IHC). Tauopathy in CatD-KO mice, as initially suggested by Gallyas silver staining, was further characterized by extensive IHC and biochemical analyses. Controls included human tau transgenic mice (JNPL3) and another mouse model of a disease (Krabbe A) characterized by pronounced lysosomal dysfunction. Additional experiments examined the effects of CatD inhibition on tau catabolism in vitro and in cultured neuroblastoma cells with inducible expression of human tau.

Results
Deletion of CatD in hAPP transgenic mice triggers large increases in cerebral Aβ, manifesting as intense, exclusively intracellular aggregates; extracellular Aβ deposition, by contrast, is neither triggered by CatD deletion, nor affected in older, haploinsufficient mice. Unexpectedly, CatD-KO mice were found to develop prominent tauopathy by just ∼ 3 weeks of age, accumulating sarkosyl-insoluble, hyperphosphorylated tau exceeding the pathology present in aged JNPL3 mice. CatD-KO mice exhibit pronounced perinuclear Gallyas silver staining reminiscent of mature neurofibrillary tangles in human AD, together with widespread phospho-tau immunoreactivity. Striking increases in sarkosyl-insoluble phospho-tau (∼ 1250%) are present in CatD-KO mice but notably absent from Krabbe A mice collected at an identical antemortem interval. In vitro and in cultured cells, we show that tau catabolism is slowed by blockade of CatD proteolytic activity, including via competitive inhibition by Aβ42.

Conclusions
Our findings support a major role for CatD in the proteostasis of both Aβ and tau in vivo. To our knowledge, the CatD-KO mouse line is the only model to develop detectable Aβ accumulation and profound tauopathy in the absence of overexpression of hAPP or human tau with disease-associated mutations. Given that tauopathy emerges from disruption of CatD, which can itself be potently inhibited by Aβ42, our findings suggest that impaired CatD activity may represent a key mechanism linking amyloid accumulation and tauopathy in AD.
Self-reporting of psychoneurophysical (PNP) symptoms in adults with four chronic diseases: a protocol for a scoping review
Authors: Rio Carielle Joy , Blumhorst Catherine , Kwiat Catherine A. , Nguyen Christopher M. , Livinski Alicia A. , Saligan Leorey N. 
Published: April 2024

Abstract
Background
Patient self-reporting of health-specific information, including symptoms, allows healthcare providers to provide more timely, personalized, and patient-centered care to meet their needs. It is critical to acknowledge that symptom reporting draws from the individual’s unique sociocultural background influencing how one perceives health and illness. This scoping review will explore whether racial groups with 4 chronic diseases (cardiovascular diseases, respiratory diseases, cancers, and diabetes) differ in self-reporting of psychoneurophysical (PNP) symptoms. The PNP symptoms of interest include depressive symptoms, fatigue, anxiety, pain, cognitive impairment, sleep impairment, mood impairment, irritability, and shortness of breath.

Methods
Four databases will be searched by a biomedical librarian: CINAHL Plus (EBSCOhost), Embase (Elsevier), PubMed (NLM), Web of Science: Core Collection (Clarivate Analytics), and limited to publications written in the English language. Two independent reviewers will screen the records’ title, abstract, and then full text and extract the data from included articles using Covidence. A third reviewer will be used for resolving disagreements. Included articles must comprise adult patients with at least one of the specified chronic diseases who self-report at least one of the specified PNP symptoms. Studies that used clinician-administered questionnaires or obtained symptom responses from primary caregiver or patient designee will be excluded. Articles on patient-reported functionality or perceived quality of life will also be excluded from the review. Two reviewers will independently extract data (e.g., demographics, study design, racial group, chronic disease, measure/scale used for self-report) from each included article using Covidence and Microsoft Excel for data cleaning and analyses.

Discussion
This scoping review may potentially identify the relevant and practical implications related to clinical decision-making and health outcomes for patients experiencing the psychoneurophysical symptoms included in this study. The authors will present how the results can be utilized in clinical practice, health policy, and research planning.

Systematic review registration
The protocol was registered on Open Science Framework (OSF) at: https://osf.io/ps7aw
EpiDiP/NanoDiP: a versatile unsupervised machine learning edge computing platform for epigenomic tumour diagnostics
Authors: Hench Jürgen , Hultschig Claus , Brugger Jon , Mariani Luigi , Guzman Raphael , Soleman Jehuda , Leu Severina , Benton Miles , Stec Irenäus Maria , Hench Ivana Bratic , Hoffmann Per , Harter Patrick , Weber Katharina J , Albers Anne , Thomas Christian , Hasselblatt Martin , Schüller Ulrich , Restelli Lisa , Capper David , Hewer Ekkehard , Diebold Joachim , Kolenc Danijela , Schneider Ulf C. , Rushing Elisabeth , della Monica Rosa , Chiariotti Lorenzo , Sill Martin , Schrimpf Daniel , von Deimling Andreas , Sahm Felix , Kölsche Christian , Tolnay Markus , Frank Stephan 
Published: April 2024

AbstractDNA methylation analysis based on supervised machine learning algorithms with static reference data, allowing diagnostic tumour typing with unprecedented precision, has quickly become a new standard of care. Whereas genome-wide diagnostic methylation profiling is mostly performed on microarrays, an increasing number of institutions additionally employ nanopore sequencing as a faster alternative. In addition, methylation-specific parallel sequencing can generate methylation and genomic copy number data. Given these diverse approaches to methylation profiling, to date, there is no single tool that allows (1) classification and interpretation of microarray, nanopore and parallel sequencing data, (2) direct control of nanopore sequencers, and (3) the integration of microarray-based methylation reference data. Furthermore, no software capable of entirely running in routine diagnostic laboratory environments lacking high-performance computing and network infrastructure exists. To overcome these shortcomings, we present EpiDiP/NanoDiP as an open-source DNA methylation and copy number profiling suite, which has been benchmarked against an established supervised machine learning approach using in-house routine diagnostics data obtained between 2019 and 2021. Running locally on portable, cost- and energy-saving system-on-chip as well as gpGPU-augmented edge computing devices, NanoDiP works in offline mode, ensuring data privacy. It does not require the rigid training data annotation of supervised approaches. Furthermore, NanoDiP is the core of our public, free-of-charge EpiDiP web service which enables comparative methylation data analysis against an extensive reference data collection. We envision this versatile platform as a useful resource not only for neuropathologists and surgical pathologists but also for the tumour epigenetics research community. In daily diagnostic routine, analysis of native, unfixed biopsies by NanoDiP delivers molecular tumour classification in an intraoperative time frame.
Examining the reliability of brain age algorithms under varying degrees of participant motion
Authors: Hanson Jamie L. , Adkins Dorthea J. , Bacas Eva , Zhou Peiran 
Published: April 2024

AbstractBrain age algorithms using data science and machine learning techniques show promise as biomarkers for neurodegenerative disorders and aging. However, head motion during MRI scanning may compromise image quality and influence brain age estimates. We examined the effects of motion on brain age predictions in adult participants with low, high, and no motion MRI scans (Original N = 148; Analytic N = 138). Five popular algorithms were tested: brainageR, DeepBrainNet, XGBoost, ENIGMA, and pyment. Evaluation metrics, intraclass correlations (ICCs), and Bland–Altman analyses assessed reliability across motion conditions. Linear mixed models quantified motion effects. Results demonstrated motion significantly impacted brain age estimates for some algorithms, with ICCs dropping as low as 0.609 and errors increasing up to 11.5 years for high motion scans. DeepBrainNet and pyment showed greatest robustness and reliability (ICCs = 0.956–0.965). XGBoost and brainageR had the largest errors (up to 13.5 RMSE) and bias with motion. Findings indicate motion artifacts influence brain age estimates in significant ways. Furthermore, our results suggest certain algorithms like DeepBrainNet and pyment may be preferable for deployment in populations where motion during MRI acquisition is likely. Further optimization and validation of brain age algorithms is critical to use brain age as a biomarker relevant for clinical outcomes.
Male involvement in maternal and child nutrition in low-income informal settlements, Nairobi, Kenya
Authors: Muthiru Ann W. , Bukachi Salome A. 
Published: April 2024

Abstract
Background
Maternal and child nutrition is a significant public health concern because adequate nutrition is essential for the health, development, and well-being of mothers and children. Men can play a critical role in improving maternal and child health, including through their involvement in the nutrition of the mother and child. However, little has been studied on male involvement in maternal and child nutrition; therefore, this qualitative exploratory study focused on the level of male involvement and factors influencing male involvement in maternal and child nutrition in low-income urban informal settings.

Methods
Qualitative data collection methods were triangulated in the exploratory study to inform the study objectives. In-depth interviews (IDIs) were conducted with 30 men and 20 women based on the inclusion criteria that they have children aged between 6 and 23 months. An additional 10 key informant interviews with stakeholders in nutrition within the study setting were also carried out. Data from the qualitative interviews were captured in audio files with informed consent and permission to record from the study participants. The interviews were transcribed and translated into English transcripts for coding and analysis. Themes were derived from the five levels of the socio-ecological model of human behavior, namely, (i) individual factors; (ii) interpersonal factors; (iii) community factors; (iv) institutional factors guided the analysis.

Results
Findings from the study revealed that personal beliefs and values, the nature of work, mistrust and stigma and discrimination, and the association clinic visits with HIV testing, were some of the factors that influenced male involvement in maternal and child nutrition.

Conclusion
It is important to recognize the potential value of research on the role of men in maternal and child nutrition and to identify ways to overcome the barriers to their involvement. By better understanding the factors that influence male involvement in maternal and child nutrition and the impact of this involvement on maternal and child nutrition, it may be possible to develop more effective interventions to promote the nutritional well-being of mothers and children.
Status epilepticus in patients with brain tumors and metastases: A multicenter cohort study of 208 patients and literature review
Authors: Rickel Johanna K. , Zeeb Daria , Knake Susanne , Urban Hans , Konczalla Jürgen , Weber Katharina J. , Zeiner Pia S. , Pagenstecher Axel , Hattingen Elke , Kemmling André , Fokas Emmanouil , Adeberg Sebastian , Wolff Robert , Sebastian Martin , Rusch Tillmann , Ronellenfitsch Michael W. , Menzler Katja , Habermehl Lena , Möller Leona , Czabanka Marcus , Nimsky Christopher , Timmermann Lars , Grefkes Christian , Steinbach Joachim P. , Rosenow Felix , Kämppi Leena , Strzelczyk Adam 
Published: April 2024

Abstract
Objective
Brain tumors and metastases account for approximately 10% of all status epilepticus (SE) cases. This study described the clinical characteristics, treatment, and short- and long-term outcomes of this population.

Methods
This retrospective, multi-center cohort study analyzed all brain tumor patients treated for SE at the university hospitals of Frankfurt and Marburg between 2011 and 2017.

Results
The 208 patients (mean 61.5 ± 14.7 years of age; 51% male) presented with adult-type diffuse gliomas (55.8%), metastatic entities (25.5%), intracranial extradural tumors (14.4%), or other tumors (4.3%). The radiological criteria for tumor progression were evidenced in 128 (61.5%) patients, while 57 (27.4%) were newly diagnosed with tumor at admission and 113 (54.3%) had refractory SE. The mean hospital length of stay (LOS) was 14.8 days (median 12.0, range 1–57), 171 (82.2%) patients required intensive care (mean LOS 8.9 days, median 5, range 1–46), and 44 (21.2%) were administered mechanical ventilation. All patients exhibited significant functional status decline (modified Rankin Scale) post-SE at discharge (p < 0.001). Mortality at discharge was 17.3% (n = 36), with the greatest occurring in patients with metastatic disease (26.4%, p = 0.031) and those that met the radiological criteria for tumor progression (25%, p < 0.001). Long-term mortality at one year (65.9%) was highest in those diagnosed with adult-type diffuse gliomas (68.1%) and metastatic disease (79.2%). Refractory status epilepticus cases showed lower survival rates than non-refractory SE patients (log-rank p = 0.02) and those with signs of tumor progression (log-rank p = 0.001).

Conclusions
SE occurrence contributed to a decline in functional status in all cases, regardless of tumor type, tumor progression status, and SE refractoriness, while long-term mortality was increased in those with malignant tumor entities, tumor progressions, and refractory SE. SE prevention may preserve functional status and improve survival in individuals with brain tumors.
Parity-time symmetry enabled ultra-efficient nonlinear optical signal processing
Authors: Kim Chanju , Lu Xinda , Kong Deming , Chen Nuo , Chen Yuntian , Oxenløwe Leif Katsuo , Yvind Kresten , Zhang Xinliang , Yang Lan , Pu Minhao , Xu Jing 
Published: April 2024

AbstractNonlinear optical signal processing (NOSP) has the potential to significantly improve the throughput, flexibility, and cost-efficiency of optical communication networks by exploiting the intrinsically ultrafast optical nonlinear wave mixing. It can support digital signal processing speeds of up to terabits per second, far exceeding the line rate of the electronic counterpart. In NOSP, high-intensity light fields are used to generate nonlinear optical responses, which can be used to process optical signals. Great efforts have been devoted to developing new materials and structures for NOSP. However, one of the challenges in implementing NOSP is the requirement of high-intensity light fields, which is difficult to generate and maintain. This has been a major roadblock to realize practical NOSP systems for high-speed, high-capacity optical communications. Here, we propose using a parity-time (PT) symmetric microresonator system to significantly enhance the light intensity and support high-speed operation by relieving the bandwidth-efficiency limit imposed on conventional single resonator systems. The design concept is the co-existence of a PT symmetry broken regime for a narrow-linewidth pump wave and near-exceptional point operation for broadband signal and idler waves. This enables us to achieve a new NOSP system with two orders of magnitude improvement in efficiency compared to a single resonator. With a highly nonlinear AlGaAs-on-Insulator platform, we demonstrate an NOSP at a data rate approaching 40 gigabits per second with a record low pump power of one milliwatt. These findings pave the way for the development of fully chip-scale NOSP devices with pump light sources integrated together, potentially leading to a wide range of applications in optical communication networks and classical or quantum computation. The combination of PT symmetry and NOSP may also open up opportunities for amplification, detection, and sensing, where response speed and efficiency are equally important.
Functional connectivity of the amygdala subregions and the antidepressant effects of repeated ketamine infusions in major depressive disorder
Authors: Liu Haiyan , Wang Chengyu , Lan Xiaofeng , Li Weicheng , Zhang Fan , Hu Zhibo , Ye Yanxiang , Ning Yuping , Zhou Yanling 
Published: April 2024

Abstract

Background
Amygdala subregion-based network dysfunction has been determined to be centrally implicated in major depressive disorder (MDD). Little is known about whether ketamine modulates amygdala subarea-related networks. We aimed to investigate the relationships between changes in the resting-state functional connectivity (RSFC) of amygdala subregions and ketamine treatment and to identify important neuroimaging predictors of treatment outcomes.

Methods
Thirty-nine MDD patients received six doses of ketamine (0.5 mg/kg). Depressive symptoms were assessed, and magnetic resonance imaging (MRI) scans were performed before and after treatment. Forty-five healthy controls underwent one MRI scan. Seed-to-voxel RSFC analyses were performed on the amygdala subregions, including the centromedial amygdala (CMA), laterobasal amygdala (LBA), and superficial amygdala subregions.

Results
Abnormal RSFC between the left LBA and the left precuneus in MDD patients is related to the therapeutic efficacy of ketamine. There were significant differences in changes in bilateral CMA RSFC with the left orbital part superior frontal gyrus and in changes in the left LBA with the right middle frontal gyrus between responders and nonresponders following ketamine treatment. Moreover, there was a difference in the RSFC of left LBA and the right superior temporal gyrus/middle temporal gyrus (STG/MTG) between responders and nonresponders at baseline, which could predict the antidepressant effect of ketamine on Day 13.

Conclusions
The mechanism by which ketamine improves depressive symptoms may be related to its regulation of RSFC in the amygdala subregion. The RSFC between the left LBA and right STG/MTG may predict the response to the antidepressant effect of ketamine.
Prevalence and Cancer-Specific Patterns of Functional Disability Among US Cancer Survivors, 2017-2022
Authors: Cao Chao , Yang Lin , Schmitz Kathryn H. , Ligibel Jennifer A. 
Published: April 2024

PURPOSE To examine the prevalence and cancer-specific patterns of functional disabilities among US cancer survivors. METHODS Data from 47,768 cancer survivors and 2,432,754 noncancer adults age 18 years and older from the 2017 to 2022 Behavioral Risk Factor Surveillance System were analyzed. Functional disabilities assessed included mobility disability (ie, serious difficulty walking or climbing stairs) and self-care disability (ie, self-reported difficulty dressing or bathing). Multivariable logistic regression models were used to assess the associations between functional disabilities and sociodemographic, lifestyle, and health-related factors. RESULTS Cancer survivors tended to be older and non-Hispanic White than noncancer adults. The prevalence of mobility disability (27.9% v 13.4%) and self-care disability (7.4% v 3.8%) were higher among cancer survivors compared with noncancer adults. After multivariable adjustments, cancer survivors were more likely to report mobility (odds ratio [OR], 1.21 [95% CI, 1.16 to 1.26]) and self-care (OR, 1.19 [95% CI, 1.10 to 1.29]) disability than noncancer adults. The prevalence of mobility (34.9% v 26.3%) and self-care disability (9.8% v 6.7%) was higher in cancer survivors who were receiving active cancer treatment than in those who had completed cancer treatment. Higher prevalence of mobility and self-care disabilities was observed in cancer survivors who were racial/ethnic minorities and with higher BMI, low physical activity, lower levels of education and/or income, comorbidities, and those experiencing cancer/treatment-related pain. Patterns of mobility and self-care disabilities varied across cancer types. CONCLUSION Over a quarter of US cancer survivors reported mobility disability, and nearly 10% reported self-care disability, with patterns varying across cancer types and treatment status. Racial/ethnic minorities, along with underserved groups and individuals with unhealthy lifestyles or comorbidities, were notably more affected by functional disabilities, underscoring the need for targeted disability prevention efforts.
Activities of living, 4: breathing
Authors: Peate Ian 
Published: April 2024

Breathing is the focus of this article in the series discussing the activities of living ( Roper et al, 2000 ). Breathing is a fundamental and vital activity of living; it plays a crucial role in the process of respiration. It is the mechanism by which gases are exchanged, primarily oxygen and carbon dioxide, with their environment. This process is essential for the production of energy through cellular respiration, which is crucial for the survival of most aerobic organisms, including humans. This article highlights the recognition that breathing is a fundamental aspect of daily life that contributes to an individual's overall wellbeing. The healthcare assistant (HCA) and assistant practitioner (AP) have a key role to play in assisting people, where needed, with this activity of living.