bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heparin treatment is associated with a delayed diagnosis of Alzheimer’s dementia in electronic health records from two large United States health systems
Authors: Readhead Benjamin , Klang Eyal , Gisladottir Undina , Vandromme Maxence , Li Li , Quiroz Yakeel T. , Arboleda-Velasquez Joseph F. , Dudley Joel T. , Tatonetti Nicholas P. , Glicksberg Benjamin S. , Reiman Eric M. 
Published: October 2024

AbstractRecent studies suggest that heparan sulfate proteoglycans (HSPG) contribute to the predisposition to, protection from, and potential treatment and prevention of Alzheimer’s disease (AD). Here, we used electronic health records (EHR) from two different health systems to examine whether heparin therapy was associated with a delayed diagnosis of AD dementia. Longitudinal EHR data from 15,183 patients from the Mount Sinai Health System (MSHS) and 6207 patients from Columbia University Medical Center (CUMC) were used in separate survival analyses to compare those who did or did not receive heparin therapy, had a least 5 years of observation, were at least 65 years old by their last visit, and had subsequent diagnostic code or drug treatment evidence of possible AD dementia. Analyses controlled for age, sex, comorbidities, follow-up duration and number of inpatient visits. Heparin therapy was associated with significant delays in age of clinical diagnosis of AD dementia, including +1.0 years in the MSMS cohort (P < 0.001) and +1.0 years in the CUMC cohort (P < 0.001). While additional studies are needed, this study supports the potential roles of heparin-like drugs and HSPGs in the protection from and prevention of AD dementia.
Exploring new horizons in neovascular age-related macular degeneration: novel mechanisms of action and future therapeutic avenues
Authors: Shirian Jonathan D. , Shukla Priya , Singh Rishi P. 
Published: October 2024

Abstract
Neovascular age-related macular degeneration (nAMD) can lead to significant vision impairment through the growth of abnormal neovascular membranes in the choroid. Despite advancements with current anti-vascular endothelial growth factor (VEGF) therapies, challenges such as frequent injections, inadequate response, and patient-related concerns persist. Emerging therapeutics aim to reduce vision-loss through a variety of mechanisms. Gene therapies, including RGX-314 and Ixo-vec, express an anti-VEGF protein, and 4D-150, expresses an anti-VEGF protein and a VEGF-C inhibitory miRNA. Anti-VEGF associated therapeutics include OPT-302, targeting VEGF-C and VEGF-D, BI 836880, which inhibits VEGF-A and Ang-2 activity, and Tarcocimab tedromer, inhibiting all VEGF-A isoforms. Agents with novel mechanisms of action include UBX1325, which inhibits an anti-apoptotic protein, Restoret (EYE103), a Wnt agonist, and the tyrosine kinase inhibitors, EYP-1901, OTX-TKI, CLS-AX, and KHK4951.
Heterogeneous afferent arteriolopathy: a key concept for understanding blood pressure–dependent renal damage
Authors: Kohagura Kentaro , Zamami Ryo , Oshiro Nanako , Shinzato Yuki , Uesugi Noriko 
Published: October 2024

AbstractHypertension, aging, and other factors are associated with arteriosclerosis and arteriolosclerosis, primary morphological features of nephrosclerosis. Although such pathological changes are not invariably linked with renal decline but are prevalent across chronic kidney disease (CKD), understanding kidney damage progression is more pragmatic than precisely diagnosing nephrosclerosis itself. Hyalinosis and medial thickening of the afferent arteriole, along with intimal thickening of small arteries, can disrupt the autoregulatory system, jeopardizing glomerular perfusion pressure given systemic blood pressure (BP) fluctuations. Consequently, such vascular lesions cause glomerular damage by inducing glomerular hypertension and ischemia at the single nephron level. Thus, the interaction between systemic BP and afferent arteriolopathy markedly influences BP-dependent renal damage progression in nephrosclerosis. Both dilated and narrowed types of afferent arteriolopathy coexist throughout the kidney, with varying proportions among patients. Therefore, optimizing antihypertensive therapy to target either glomerular hypertension or ischemia is imperative. In recent years, clinical trials have indicated that combining renin–angiotensin system inhibitors (RASis) and sodium–glucose transporter 2 inhibitors (SGLT2is) is superior to using RASis alone in slowing renal function decline, despite comparable reductions in albuminuria. The superior efficacy of SGLT2is may arise from their beneficial effects on both glomerular hypertension and renal ischemia. A comprehensive understanding of the interaction between systemic BP and heterogeneous afferent arteriolopathy is pivotal for optimizing therapy and mitigating renal decline in patients with CKD of any etiology. Therefore, in this comprehensive review, we explore the role of afferent arteriolopathy in BP-dependent renal damage.
Light-harvesting properties of photocatalyst supports—no photon left behind
Authors: Tountas Athanasios A. , Dreher Anselm , Zhou Wenjie , Mohan Abhinav , Kherani Nazir P. , Ozin Geoffrey A. , Sain Mohini M. 
Published: October 2024

AbstractIn this work, we set out to elucidate the light-harvesting properties of various random and ordered photocatalyst supports (PSs) with different macropore sizes. To accomplish this, we propose two studies of increasing relevance, enabled by computed tomography (CT) reconstructions and ray-tracing COMSOL Multiphysics simulations: (a) a 360-degree light release study approximating a PS situated within a compound parabolic concentrator (CPC) or cylindrical LED reactor with open ends; and (b) the same system as before but with closed ends. The ordered geometry is of interest, as it can be 3D printed at scale with a tailored morphology and porosity, and it can potentially be refined using machine learning models to optimize its light-harvesting properties. As will be shown, the local volumetric light absorption (LVLA) data suggests that an ordered PS with a more open pore interior and a smaller pore exterior would begin to approach the more isophotonic light-harvesting properties of random PSs.
Chemical inhibition of the integrated stress response impairs the ubiquitin-proteasome system
Authors: Xu Shanshan , Gierisch Maria E. , Barchi Enrica , Poser Ina , Alberti Simon , Salomons Florian A. , Dantuma Nico P. 
Published: October 2024

AbstractInhibitors of the integrated stress response (ISR) have been used to explore the potential beneficial effects of reducing the activation of this pathway in diseases. As the ISR is in essence a protective response, there is, however, a risk that inhibition may compromise the cell’s ability to restore protein homeostasis. Here, we show that the experimental compound ISRIB impairs degradation of proteins by the ubiquitin-proteasome system (UPS) during proteotoxic stress in the cytosolic, but not nuclear, compartment. Accumulation of a UPS reporter substrate that is intercepted by ribosome quality control was comparable to the level observed after blocking the UPS with a proteasome inhibitor. Consistent with impairment of the cytosolic UPS, ISRIB treatment caused an accumulation of polyubiquitylated and detergent insoluble defective ribosome products (DRiPs) in the presence of puromycin. Our data suggest that the persistent protein translation during proteotoxic stress in the absence of a functional ISR increases the pool of DRiPs, thereby hindering the efficient clearance of cytosolic substrates by the UPS.
Methodological concerns underlying a lack of evidence for cultural heterogeneity in the replication of psychological effects
Authors: Schimmelpfennig Robin , Spicer Rachel , White Cindel J. M. , Gervais Will , Norenzayan Ara , Heine Steven , Henrich Joseph , Muthukrishna Michael 
Published: October 2024

AbstractThe multi-site replication study, Many Labs 2, concluded that sample location and setting did not substantially affect the replicability of findings. Here, we examine theoretical and methodological considerations for a subset of the analyses, namely exploratory tests of heterogeneity in the replicability of studies between “WEIRD and less-WEIRD cultures”. We conducted a review of literature citing the study, a re-examination of the existing cultural variability, a power stimulation for detecting cultural heterogeneity, and re-analyses of the original exploratory tests. Findings indicate little cultural variability and low power to detect cultural heterogeneity effects in the Many Labs 2 data, yet the literature review indicates the study is cited regarding the moderating role of culture. Our reanalysis of the data found that using different operationalizations of culture slightly increased effect sizes but did not substantially alter the conclusions of Many Labs 2. Future studies of cultural heterogeneity can be improved with theoretical consideration of which effects and which cultures are likely to show variation as well as a priori methodological planning for appropriate operationalizations of culture and sufficient power to detect effects.
DELE1 maintains muscle proteostasis to promote growth and survival in mitochondrial myopathy
Authors: Lin Hsin-Pin , Petersen Jennifer D , Gilsrud Alexandra J , Madruga Angelo , D’Silva Theresa M , Huang Xiaoping , Shammas Mario K , Randolph Nicholas P , Johnson Kory R , Li Yan , Jones Drew R , Pacold Michael E , Narendra Derek P 
Published: October 2024

AbstractMitochondrial dysfunction causes devastating disorders, including mitochondrial myopathy, but how muscle senses and adapts to mitochondrial dysfunction is not well understood. Here, we used diverse mouse models of mitochondrial myopathy to show that the signal for mitochondrial dysfunction originates within mitochondria. The mitochondrial proteins OMA1 and DELE1 sensed disruption of the inner mitochondrial membrane and, in response, activated the mitochondrial integrated stress response (mt-ISR) to increase the building blocks for protein synthesis. In the absence of the mt-ISR, protein synthesis in muscle was dysregulated causing protein misfolding, and mice with early-onset mitochondrial myopathy failed to grow and survive. The mt-ISR was similar following disruptions in mtDNA maintenance (Tfam knockout) and mitochondrial protein misfolding (CHCHD10 G58R and S59L knockin) but heterogenous among mitochondria-rich tissues, with broad gene expression changes observed in heart and skeletal muscle and limited changes observed in liver and brown adipose tissue. Taken together, our findings identify that the DELE1 mt-ISR mediates a similar response to diverse forms of mitochondrial stress and is critical for maintaining growth and survival in early-onset mitochondrial myopathy.
Strong turbulence and magnetic coherent structures in the interstellar medium
Authors: Ntormousi Evangelia , Vlahos Loukas , Konstantinou Anna , Isliker Heinz 
Published: October 2024

Context. Magnetic turbulence is classified as weak or strong based on the relative amplitude of the magnetic field fluctuations compared to the mean field. These two classes have different energy transport properties.
Aims. The purpose of this study is to analyze turbulence in the interstellar medium (ISM) based on this classification. Specifically, we examined the ISM of simulated galaxies to detect evidence of strong magnetic turbulence and provide statistics on the associated magnetic coherent structures (MCoSs), such as current sheets, that arise in this context.
Methods. We analyzed magnetohydrodynamic galaxy simulations with different initial magnetic field structures (either completely ordered or completely random) and recorded statistics on the magnetic field fluctuations (δB/B0) and the MCoSs, which are defined here as regions where the current density surpasses a certain threshold. We also studied the MCoS sizes and kinematics.
Results. The magnetic field disturbances in both models follow a log-normal distribution, peaking at values close to unity; this distribution turns into a power law at large values (δB/B0 > 1), which is consistent with strong magnetic turbulence The current densities are widely distributed, with non-power-law deviations from a log-normal at the largest values. These deviating values of the current density define MCoSs. We find that, in both models, MCoSs are fractally distributed in space, with a typical volume-filling factor of about 10%, and tend to coincide with peaks of star formation density. Their fractal dimension is close to unity on sub-kiloparsec scales, and between 2 and 3 on larger scales. These values are consistent with MCoSs having a sheet-like or filament-like morphology.
Conclusions. Our work challenges the prevailing paradigm of weak magnetic turbulence in the ISM by demonstrating that strong magnetic disturbances can occur even when the initial magnetic field is completely ordered. This strong magnetic turbulence arises self-consistently from differential rotation and supernova feedback. Our findings provide a foundation for a magnetic turbulence description of the galactic ISM that includes strong fluctuations of the magnetic field.
Pulmonale Sarkoidose
Authors: Jentzsch Benedikt , Jouanjan Louis , Frye Björn Christian 
Published: October 2024

ZUSAMMENFASSUNGSarkoidose ist eine seltene, granulomatöse Erkrankung unklarer Ätiologie, die vor allem das lymphatische System und die Lunge befällt, jedoch auch alle anderen Organe betreffen kann. Die Diagnose wird anhand passender klinischer Symptome, dem histologischen Nachweis von nicht nekrotisierenden Granulomen sowie dem Ausschluss relevanter Differenzialdiagnosen gestellt. Der histologische Nachweis von Granulomen gelingt häufig mittels endobronchialer ultraschallgesteuerter transbronchialer Feinnadelbiopsie der thorakalen Lymphknoten, alternativ können bronchoskopisch Schleimhaut- oder transbronchiale Parenchymbiopsien zur Diagnose vorgenommen werden. Die Entscheidung für eine immunsuppressive Therapie sollte vor allem unter Berücksichtigung der Nebenwirkungen dann getroffen werden, wenn die Sarkoidose die Lebensqualität der*s Betroffenen reduziert oder Organfunktionen einschränkt. Die Therapie erfolgt primär mit Kortikosteroiden und kann in der Zweitlinientherapie um Azathioprin oder Methotrexat (oder andere DMARD) als steroidsparende Medikamente erweitert werden. Die klinische Verlaufskontrolle zielt auf das Monitoring der Organfunktionen (z. B. Lungenfunktion) und der Lebensqualität.
Typ-1-Interferonopathien
Authors: Wege Lisa , Lee-Kirsch Min Ae 
Published: October 2024

ZUSAMMENFASSUNGDie Typ-1-Interferonopathien umfassen eine klinisch heterogene Gruppe seltener Erkrankungen, die auf einer genetisch bedingten Fehlfunktion des angeborenen Immunsystems beruhen. Zentrales Merkmal ist eine chronisch gesteigerte Aktivität der antiviralen Typ-1-Interferon(IFN)-Achse, die zu einer Immundysregulation führt. Das klinische Spektrum der Typ-1-Interferonopathien ist breit und primär durch Autoinflammation und Autoimmunität gekennzeichnet, wobei bei einigen Erkrankungen auch eine Infektneigung auftreten kann. Neben systemischen Zeichen wie Fieberschüben und erhöhten Entzündungswerten können verschiedene organspezifische Manifestationen auftreten. Pathogenetisch liegen den Typ-1-Interferonopathien Störungen des Metabolismus und der immunologischen Erkennung von intrazellulären Nukleinsäuren zugrunde. Da einige Erkrankungen therapeutisch auf eine immunmodulatorische Intervention ansprechen, die der inadäquaten Typ-1-IFN-Aktvierung entgegenwirkt, ist eine möglichst frühzeitige Diagnose von großer Bedeutung.
Salbe, Creme, Gel? Dermatika für jede Indikation!
Authors: Wendland Matthias 
Published: October 2024

SummaryFür die topische Anwendung stehen je nach Indikation unterschiedliche Zubereitungen bereit, darunter insbesondere Salben, Cremes, Lösungen, Gele und Puder. Während Salben über eine ausschließlich fette Grundlage verfügen, kommen in Cremes ein Wasseranteil und ein geeigneter Emulgator dazu, indes Gele meist zu über 95 % aus Wasser bestehen. Aufgrund ihrer Zusammensetzung und spezifischen Eigenschaften eignen sich Salben und Wasser-in-Öl-Cremes insbesondere für trockene und schuppende Haut und sind vorteilhaft, wenn eine lange und tiefe Wirkung erwünscht ist. Gele bieten sich bei akuter Entzündung, Schmerz und Schwellung, Öl-in-Wasser-Cremes und feuchte Umschläge bei exsudativen Dermatosen an.
Fieberklee - nah am Wasser gebaut
Authors: Lorenz Daniel 
Published: October 2024

SummaryAuf der gesamten Nordhalbkugel ist der Fieberklee (Menyanthes trifoliata) in Feuchtgebieten zu finden. Diese bemerkenswerte Pflanze, die auch unter den Namen Bitterklee oder Wasserklee bekannt ist, wird seit Jahrhunderten wegen ihrer heilenden Eigenschaften geschätzt.
Alles fließt von Kopf bis Fuß
Authors: Corts Magga 
Published: October 2024

SummaryMithilfe zirkulatorischer Behandlungstechniken werden der Liquor-, der Lymph- und der Blutfluss angeregt, um den Stoffwechsel, die Zellregeneration und das Immunsystem zu unterstützen und Stauungen entgegenzuwirken. Der Beitrag erläutert die verschiedenen Systeme, beleuchtet den parasympathischen Einfluss auf den menschlichen Organismus und stellt wichtige Behandlungsschritte von Kopf bis Fuß vor. Für die gesamte Homöostase hilfreich können die beschriebenen Techniken manuelle sowie medikamentöse Therapien ergänzenund zu einem wichtigen Bestandteil naturheilkundlicher Konzepte werden.
Schweiß lass nach!
Authors: Welsch Katja 
Published: October 2024

SummaryDie primäre Hyperhidrose ist eine idiopathische Erkrankung, lässt sich also nicht einer bestimmten Ursache zuordnen. Da die Klassische Homöopathie symptombezogen vorgeht, lässt sich in vielen Fällen ein passendes Homöopathikum für das übermäßige Schwitzen finden, zum Beispiel das häufig verordnete Sulfur. Viele homöopathische Arzneien haben einen Bezug zu Schwitzen und Schweiß. Daher ist es umso wichtiger, für die Mittelfindung weitere begleitende Symptome oder Modalitäten herauszufinden.
Clinical evaluation of a novel single-use therapeutic gastroscope: a pilot feasibility study
Authors: Römmele Christoph , Ayoub Mousa , Wanzl Julia , Tadic Vidan , Braun Georg , Weber Tobias , Scheppach Markus Wolfgang , Roser David , Matic Katharina , Nagl Sandra , Messmann Helmut , Ebigbo Alanna 
Published: October 2024

Abstract
Background The trend toward disposable products in gastrointestinal endoscopy, including single-use endoscopes, remains undeterred, even though crucial questions of sustainability and performance have not been sufficiently studied. The first single-use therapeutic gastroscope was recently approved in Europe, but clinical data to support its use are currently lacking. We aimed to evaluate the performance of this novel device in routine procedures requiring a large working channel.
Methods Between January and May 2024, consecutive patients with an indication for therapeutic gastroscopy were included prospectively. The primary outcome was intraprocedural technical success rate.
Results Eight gastrointestinal bleedings, two pancreatic necrosectomies, four foreign body removals, four stent placements, and two cryo-balloon ablations were performed. The technical success rate was 84% (16/19 patients). Crossover to a standard endoscope was required in three procedures. Clinical success was achieved in all cases with technical success. Overall user experience was 3.2 on a Likert scale of 1–5. No adverse events were reported.
Conclusions The single-use therapeutic gastroscope demonstrated feasibility in various therapeutic procedures; however, a 16% crossover rate and fair user assessment score suggest that further technical improvements to the device are necessary.
Single Institution Experience with Lumbar Drainage and Subarachnoid Hemorrhage
Authors: Coggins William S. , Banko Lauren E. , Chokhani Purav , Rushing Elise G. , Necarsulmer Julie , Sasaki-Adams Deanna 
Published: October 2024

Abstract
Introduction In our article, we evaluate the effect of lumbar drainage on delayed cerebral ischemia and requirements for permanent cerebrospinal fluid diversion in patients with aneurysmal subarachnoid hemorrhage.
Methods We performed a retrospective cohort study from 2014 to 2023 at the University of Arkansas for Medical Sciences (UAMS) examining factors associated with patients (n = 150) who had aneurysmal subarachnoid hemorrhage and a lumbar drain placed. The main outcomes examined were incidence of delayed cerebral ischemia, need for permanent cerebrospinal fluid diversion, and neurologic outcomes at discharge that were compared to currently published standards.
Results We failed to appreciate a reduced occurrence of delayed cerebral ischemia (37.3% with the current literature supporting rates of 20–30%); however, we did find a low rate of requiring permanent cerebrospinal fluid diversion (12% compared to 10–20% in the current literature) with overall good neurologic outcomes at discharge (∼69% of patients had a Glasgow Outcome Scale [GOS] of 4–5 at discharge). Patients with GOS ≥ 4 at discharge were noted to be more likely to have more days or lumbar drainage and less likely to be older than 65 years, have had an external ventricular drain placed, and have experienced delayed cerebral ischemia.
Conclusion Lumbar drainage is a potentially useful adjunct in the management of secondary neurologic injury in subarachnoid hemorrhage.
Radiomic Applications in Skull Base Pathology: A Systematic Review of Potential Clinical Uses
Authors: Tenhoeve Samuel A. , Lefler Sydnee , Brown Julian , Owens Monica-Rae , Rawson Clayton , Tabachnick Dora R. , Shaik Kamal , Karsy Michael 
Published: October 2024

Abstract
Objectives Radiomics involves the extraction and analysis of numerous quantitative features of medical imaging which can add more information from radiological images often beyond initial comprehension of a clinician. Unlike deep learning, radiomics allows some understanding of identified quantitative features for clinical prediction. We sought to explore the current state of radiomics applications in the skull base literature.
Methods A systematic review of studies evaluating radiomics in skull base was performed, including those with and without machine-learning approaches. Studies were summarized into thematic elements as well as specific pathologies.
Results A total of 102 studies with 26,280 radiographic images were included. The earliest radiomic study was published in 2017 with exponential growth in research since then. Most studies focused on tumor diagnosis (40.8%), followed by tumor prognosis (31.1%), automated segmentation (16.5%), other applications (7.8%), and lastly prediction of intraoperative features (3.9%). Pituitary adenomas (41.7%) and vestibular schwannomas (18.4%) represented the most commonly evaluated pathologies; however, radiomics could be applied to a heterogeneous collection of skull base pathologies. The average study included 258 ± 677 cases (range 4; 6,755).
Conclusion Radiomics offers many functions in treating skull base pathology and will likely be an essential component of future clinical care. Larger sample sizes, validation of predictive models, and clinical application are needed. Further investigation into the strengths and weaknesses of radiomic applications in skull base treatments is warranted.