bluuebunny/crossref_metadata_2025_split huggingface dataset:
CRLF1 bridges AKT and mTORC2 through SIN1 to inhibit pyroptosis and enhance chemo-resistance in ovarian cancer
Authors: Xiang Cong , Chen Li , Zhu Shilei , Chen Yue , Huang Haodong , Yang Chunmao , Chi Yugang , Wang Yanzhou , Lei Yunlong , Cai Xiongwei 
Published: September 2024

AbstractOvarian cancer, the second most leading cause of gynecologic cancer mortality worldwide, is challenged by chemotherapy resistance, presenting a significant hurdle. Pyroptosis, an inflammation-linked programmed cell death mediated by gasdermins, has been shown to impact chemoresistance when dysregulated. However, the mechanisms connecting pyroptosis to chemotherapy resistance in ovarian cancer are unclear. We found that cytokine receptor-like factor 1 (CRLF1) is a novel component of mTORC2, enhancing AKT Ser473 phosphorylation through strengthening the interaction between AKT and stress-activated protein kinase interacting protein 1 (SIN1), which in turn inhibits the mitogen-activated protein kinase kinase kinase 5 (ASK1)-JNK-caspase-3-gasdermin E pyroptotic pathway and ultimately confers chemoresistance. High CRLF1-expressing tumors showed sensitivity to AKT inhibition but tolerance to cisplatin. Remarkably, overexpression of binding-defective CRLF1 variants impaired AKT-SIN1 interaction, promoting pyroptosis and chemosensitization. Thus, CRLF1 critically regulates chemoresistance in ovarian cancer by modulating AKT/SIN1-dependent pyroptosis. Binding-defective CRLF1 variants could be developed as tumor-specific polypeptide drugs to enhance chemotherapy for ovarian cancer.
NEK6 dampens FOXO3 nuclear translocation to stabilize C-MYC and promotes subsequent de novo purine synthesis to support ovarian cancer chemoresistance
Authors: Liu Jingchun , Wang Haoyu , Wan Huanzhi , Yang Jiang , Gao Likun , Wang Zhi , Zhang Xiaoyi , Han Wuyue , Peng Jiaxin , Yang Lian , Hong Li 
Published: September 2024

AbstractDe novo purine synthesis metabolism plays a crucial role in tumor cell survival and malignant progression. However, the specific impact of this metabolic pathway on chemoresistance in ovarian cancer remains unclear. This study aims to elucidate the influence of de novo purine synthesis on chemoresistance in ovarian cancer and its underlying regulatory mechanisms. We analyzed metabolic differences between chemosensitive and chemoresistant ovarian cancer tissues using mass spectrometry-based metabolomics. Cell growth, metabolism, chemoresistance, and DNA damage repair characteristics were assessed in vitro using cell line models. Tumor growth and chemoresistance were assessed in vivo using ovarian cancer xenograft tumors. Intervention of purines and NEK6-mediated purine metabolism on chemoresistance was investigated at multiple levels. Chemoresistant ovarian cancers exhibited higher purine abundance and NEK6 expression. Inhibiting NEK6 led to decreased de novo purine synthesis, resulting in diminished chemoresistance in ovarian cancer cells. Mechanistically, NEK6 directly interacted with FOXO3, contributing to the phosphorylation of FOXO3 at S7 through its kinase activity, thereby inhibiting its nuclear translocation. Nuclear FOXO3 promoted FBXW7 transcription, leading to c-MYC ubiquitination and suppression of de novo purine synthesis. Paeonol, by inhibiting NEK6, suppressed de novo purine synthesis and enhanced chemosensitivity. The NEK6-mediated reprogramming of de novo purine synthesis emerges as a critical pathway influencing chemoresistance in ovarian cancer. Paeonol exhibits the potential to interfere with NEK6, thereby inhibiting chemoresistance.
Spermidine-eIF5A axis is essential for muscle stem cell activation via translational control
Authors: Zhang Qianying , Han Wanhong , Wu Rimao , Deng Shixian , Meng Jiemiao , Yang Yuanping , Li Lili , Sun Mingwei , Ai Heng , Chen Yingxi , Liu Qinyao , Gao Tian , Niu Xingchen , Liu Haixia , Zhang Li , Zhang Dan , Chen Meihong , Yin Pengbin , Zhang Licheng , Tang Peifu , Zhu Dahai , Zhang Yong , Li Hu 
Published: September 2024

AbstractAdult skeletal muscle stem cells, also known satellite cells (SCs), are quiescent and activate in response to injury. However, the activation mechanisms of quiescent SCs (QSCs) remain largely unknown. Here, we investigated the metabolic regulation of SC activation by identifying regulatory metabolites that promote SC activation. Using targeted metabolomics, we found that spermidine acts as a regulatory metabolite to promote SC activation and muscle regeneration in mice. Mechanistically, spermidine activates SCs via generating hypusinated eIF5A. Using SC-specific eIF5A-knockout (KO) and Myod-KO mice, we further found that eIF5A is required for spermidine-mediated SC activation by controlling MyoD translation. More significantly, depletion of eIF5A in SCs results in impaired muscle regeneration in mice. Together, the findings of our study define a novel mechanism that is essential for SC activation and acts via spermidine-eIF5A-mediated MyoD translation. Our findings suggest that the spermidine-eIF5A axis represents a promising pharmacological target in efforts to activate endogenous SCs for the treatment of muscular disease.
Interim safety and efficacy of gene therapy for RLBP1-associated retinal dystrophy: a phase 1/2 trial
Authors: Kvanta Anders , Rangaswamy Nalini , Holopigian Karen , Watters Christine , Jennings Nicki , Liew Melissa S. H. , Bigelow Chad , Grosskreutz Cynthia , Burstedt Marie , Venkataraman Abinaya , Westman Sofie , Geirsdottir Asbjörg , Stasi Kalliopi , André Helder 
Published: September 2024

AbstractGene therapy holds promise for treatment of inherited retinal dystrophies, a group of rare genetic disorders characterized by severe loss of vision. Here, we report up to 3-year pre-specified interim safety and efficacy results of an open-label first-in-human dose-escalation phase 1/2 gene therapy clinical trial in 12 patients with retinal dystrophy caused by biallelic mutations in the retinaldehyde-binding protein 1 (RLBP1) gene of the visual cycle. The primary endpoints were systemic and ocular safety and recovery of dark adaptation. Secondary endpoints included microperimetry, visual field sensitivity, dominant eye test and patient-reported outcomes. Subretinal delivery of an adeno-associated viral vector (AAV8-RLBP1) was well tolerated with dose-dependent intraocular inflammation which responded to corticosteroid treatment, and focal atrophy of the retinal pigment epithelium as the dose limiting toxicity. Dark adaptation kinetics, the primary efficacy endpoint, improved significantly in all dose-cohorts. Treatment with AAV8-RLBP1 resulted in the resolution of disease-related retinal deposits, suggestive of successful restoration of the visual cycle. In conclusion, to date, AAV8-RLBP1 has shown preliminary safety and efficacy in patients with RLBP1-associated retinal dystrophy. Trial number: NCT03374657.
Lethal Borna disease virus 1 infections of humans and animals – in-depth molecular epidemiology and phylogeography
Authors: Ebinger Arnt , Santos Pauline D. , Pfaff Florian , Dürrwald Ralf , Kolodziejek Jolanta , Schlottau Kore , Ruf Viktoria , Liesche-Starnecker Friederike , Ensser Armin , Korn Klaus , Ulrich Reiner , Fürstenau Jenny , Matiasek Kaspar , Hansmann Florian , Seuberlich Torsten , Nobach Daniel , Müller Matthias , Neubauer-Juric Antonie , Suchowski Marcel , Bauswein Markus , Niller Hans-Helmut , Schmidt Barbara , Tappe Dennis , Cadar Daniel , Homeier-Bachmann Timo , Haring Viola C. , Pörtner Kirsten , Frank Christina , Mundhenk Lars , Hoffmann Bernd , Herms Jochen , Baumgärtner Wolfgang , Nowotny Norbert , Schlegel Jürgen , Ulrich Rainer G. , Beer Martin , Rubbenstroth Dennis 
Published: September 2024

AbstractBorna disease virus 1 (BoDV-1) is the causative agent of Borna disease, a fatal neurologic disorder of domestic mammals and humans, resulting from spill-over infection from its natural reservoir host, the bicolored white-toothed shrew (Crocidura leucodon). The known BoDV-1-endemic area is remarkably restricted to parts of Germany, Austria, Switzerland and Liechtenstein. To gain comprehensive data on its occurrence, we analysed diagnostic material from suspected BoDV-1-induced encephalitis cases based on clinical and/or histopathological diagnosis. BoDV-1 infection was confirmed by RT-qPCR in 207 domestic mammals, 28 humans and seven wild shrews. Thereby, this study markedly raises the number of published laboratory-confirmed human BoDV-1 infections and provides a first comprehensive summary. Generation of 136 new BoDV-1 genome sequences from animals and humans facilitated an in-depth phylogeographic analysis, allowing for the definition of risk areas for zoonotic BoDV-1 transmission and facilitating the assessment of geographical infection sources. Consistent with the low mobility of its reservoir host, BoDV-1 sequences showed a remarkable geographic association, with individual phylogenetic clades occupying distinct areas. The closest genetic relatives of most human-derived BoDV-1 sequences were located at distances of less than 40 km, indicating that spill-over transmission from the natural reservoir usually occurs in the patient´s home region.
A whole-body micro-CT scan library that captures the skeletal diversity of Lake Malawi cichlid fishes
Authors: Bucklow Callum V. , Genner Martin J. , Turner George F. , Maclaine James , Benson Roger , Verd Berta 
Published: September 2024

AbstractHere we describe a dataset of freely available, readily processed, whole-body μCT-scans of 56 species (116 specimens) of Lake Malawi cichlid fishes that captures a considerable majority of the morphological variation present in this remarkable adaptive radiation. We contextualise the scanned specimens within a discussion of their respective ecomorphological groupings and suggest possible macroevolutionary studies that could be conducted with these data. In addition, we describe a methodology to efficiently μCT-scan (on average) 23 specimens per hour, limiting scanning time and alleviating the financial cost whilst maintaining high resolution. We demonstrate the utility of this method by reconstructing 3D models of multiple bones from multiple specimens within the dataset. We hope this dataset will enable further morphological study of this fascinating system and permit wider-scale comparisons with other cichlid adaptive radiations.
Unmasking and quantifying racial bias of large language models in medical report generation
Authors: Yang Yifan , Liu Xiaoyu , Jin Qiao , Huang Furong , Lu Zhiyong 
Published: September 2024

Abstract
Background
Large language models like GPT-3.5-turbo and GPT-4 hold promise for healthcare professionals, but they may inadvertently inherit biases during their training, potentially affecting their utility in medical applications. Despite few attempts in the past, the precise impact and extent of these biases remain uncertain.

Methods
We use LLMs to generate responses that predict hospitalization, cost and mortality based on real patient cases. We manually examine the generated responses to identify biases.

Results
We find that these models tend to project higher costs and longer hospitalizations for white populations and exhibit optimistic views in challenging medical scenarios with much higher survival rates. These biases, which mirror real-world healthcare disparities, are evident in the generation of patient backgrounds, the association of specific diseases with certain racial and ethnic groups, and disparities in treatment recommendations, etc.

Conclusions
Our findings underscore the critical need for future research to address and mitigate biases in language models, especially in critical healthcare applications, to ensure fair and accurate outcomes for all patients.
Lipidomic biomarkers in plasma correlate with disease severity in adrenoleukodystrophy
Authors: Jaspers Yorrick R. J. , Yska Hemmo A. F. , Bergner Caroline G. , Dijkstra Inge M. E. , Huffnagel Irene C. , Voermans Marije M. C. , Wever Eric , Salomons Gajja S. , Vaz Frédéric M. , Jongejan Aldo , Hermans Jill , Tryon Rebecca K. , Lund Troy C. , Köhler Wolfgang , Engelen Marc , Kemp Stephan 
Published: September 2024

Abstract
Background
X-linked adrenoleukodystrophy (ALD) is a neurometabolic disorder caused by pathogenic variants in ABCD1 resulting very long-chain fatty acids (VLCFA) accumulation in plasma and tissues. Males can present with various clinical manifestations, including adrenal insufficiency, spinal cord disease, and leukodystrophy. Female patients typically develop spinal cord disease and peripheral neuropathy. Predicting the clinical outcome of an individual patient remains impossible due to the lack of genotype-phenotype correlation and predictive biomarkers.

Methods
The availability of a large prospective cohort of well-characterized patients and associated biobank samples allowed us to investigate the relationship between lipidome and disease severity in ALD. We performed a lipidomic analysis of plasma samples from 24 healthy controls, 92 male and 65 female ALD patients.

Results
Here we show that VLCFA are incorporated into different lipid classes, including lysophosphatidylcholines, phosphatidylcholines, triglycerides, and sphingomyelins. Our results show a strong association between higher levels of VLCFA-containing lipids and the presence of leukodystrophy, adrenal insufficiency, and severe spinal cord disease in male ALD patients. In female ALD patients, VLCFA-lipid levels correlate with X-inactivation patterns in blood mononuclear cells, and higher levels are associated with more severe disease manifestations. Finally, hematopoietic stem cell transplantation significantly reduces, but does not normalize, plasma C26:0-lysophosphatidylcholine levels in male ALD patients. Our findings are supported by the concordance of C26:0-lysophosphatidylcholine and total VLCFA analysis with the lipidomics results.

Conclusions
This study reveals the profound impact of ALD on the lipidome and provides potential biomarkers for predicting clinical outcomes in ALD patients.
The global phosphorylation landscape of mouse oocytes during meiotic maturation
Authors: Sun Hongzheng , Han Longsen , Guo Yueshuai , An Huiqing , Wang Bing , Zhang Xiangzheng , Li Jiashuo , Jiang Yingtong , Wang Yue , Sun Guangyi , Zhu Shuai , Tang Shoubin , Ge Juan , Chen Minjian , Guo Xuejiang , Wang Qiang 
Published: September 2024

AbstractPhosphorylation is a key post-translational modification regulating protein function and biological outcomes. However, the phosphorylation dynamics orchestrating mammalian oocyte development remains poorly understood. In the present study, we apply high-resolution mass spectrometry-based phosphoproteomics to obtain the first global in vivo quantification of mouse oocyte phosphorylation. Of more than 8000 phosphosites, 75% significantly oscillate and 64% exhibit marked upregulation during meiotic maturation, indicative of the dominant regulatory role. Moreover, we identify numerous novel phosphosites on oocyte proteins and a few highly conserved phosphosites in oocytes from different species. Through functional perturbations, we demonstrate that phosphorylation status of specific sites participates in modulating critical events including metabolism, translation, and RNA processing during meiosis. Finally, we combine inhibitor screening and enzyme-substrate network prediction to discover previously unexplored kinases and phosphatases that are essential for oocyte maturation. In sum, our data define landscape of the oocyte phosphoproteome, enabling in-depth mechanistic insights into developmental control of germ cells.
Thermodynamic phase control of Cu–Sn alloy electrocatalysts for selective CO2 reduction
Authors: Go Soohyun , Kwon Woosuck , Hong Deokgi , Lee Taemin , Oh Sang-Ho , Bae Daewon , Kim Jeong-Heon , Lim Seolha , Joo Young-Chang , Nam Dae-Hyun 
Published: September 2024

Cu–Sn alloy catalyst can regulate CO2 reduction reaction (CO2RR) intermediates. However, previous Cu–Sn alloy catalysts were limited in phase control. Here, we report thermodynamic based Cu–Sn bimetallic phase control and selective CO2RR.
Discontinuous Galerkin finite element method for the continuum radiative transfer problem inside axis-symmetric circumstellar envelopes
Authors: Perdigon J. , Faurobert M. , Niccolini G. 
Published: September 2024

Context. The study of the continuum radiative transfer problem inside circumstellar envelopes is both a theoretical and numerical challenge, especially in the frequency-dependent and multi-dimensional case. While approximate methods are easier to handle numerically, they often fail to accurately describe the radiation field inside complex geometries. For these cases, it is necessary to directly solve the radiative transfer equation numerically.
Aims. We investigate the accuracy of the discontinuous Galerkin finite element method (DGFEM hereafter) applied to the frequency-dependent two-dimensional radiative transfer problem, and coupled with the radiative equilibrium equation. We next used this method in the context of axis-symmetric circumstellar envelopes.
Methods. The DGFEM is a variant of finite element methods. It employs discontinuous elements and flux integrals along their boundaries, ensuring local flux conservation. However, as opposed to the classical finite element methods, the solution is discontinuous across element edges. We implemented this approach in a code and tested its accuracy by comparing our results with the benchmarks from the literature.
Results. For all the tested cases, the temperatures profiles agree within one percent. Additionally, the emerging spectral energy distributions (SEDs) and images, obtained by ray-tracing techniques from the DGFEM emissivity, agree on average within 5% and 10%, respectively.
Conclusions. We show that the DGFEM can accurately describe the continuum radiative transfer problem inside axis-symmetric circumstellar envelopes. Consecutively the emerging SEDs and images are also well reproduced. The DGFEM provides an alternative method (other than Monte-Carlo methods for instance) for solving the radiative transfer equation, and it could be used in cases that are more difficult to handle with the other methods.
Die Weiterbildungsstruktur der Handchirurgie in Deutschland –
Auswertung eines Online-Fragebogens
Authors: Rische Christian , Schmiechen Jule , Kremer Thomas , Rein Susanne 
Published: September 2024

Zusammenfassung
Hintergrund Da einige europäische Länder bereits eine eigene
handchirurgische Facharztbezeichnung haben und andererseits in Deutschland die
Weiterbildungszeit der Zusatzbezeichnung für Handchirurgie von drei auf zwei
Jahre reduziert wurde, wird die Weiterbildungsstruktur des Fachgebietes
Handchirurgie intensiv diskutiert.
Ziel der Arbeit Das Ziel der vorliegenden Studie war es, die aktuelle
Situation der handchirurgischen Weiterbildung in Deutschland zu evaluieren.
Material und Methoden Es wurden zwei separate Online-Fragebögen zur
Selbsteinschätzung von Weiterbildungsassistenten und Weiterbildern in
handchirurgischen Abteilungen entwickelt. Der Fragebogen für
Weiterbildungsassistenten umfasste 29 Fragen und der für Weiterbilder 24 Fragen.
Erhoben wurden neben demografischen Daten und chirurgischen Trainingsparametern
auch der Umgang mit Lehrmedien sowie die Zufriedenheit. Der Online-Fragebogen
wurde über den E-Mail-Verteiler der Deutschen Gesellschaft für Handchirurgie im
Untersuchungszeitraum Mai bis Juli 2023 zur Verfügung gestellt.
Ergebnisse Es nahmen 54 Weiterbildungsassistenten (WBA) und 94
Weiterbilder (WB) an der Umfrage teil. Unter den WBA befanden sich 70% Frauen in
der Weiterbildung, währenddessen 65% Männer als WB fungieren. Die
handchirurgische Ausbildung erfolgte hauptsächlich in Kliniken der Schwerpunkt-
(p=0,012) und Maximalversorgung (p<0,001). Digitale Lehrmedien wurden
signifikant häufiger von WBA im Vergleich zu den WB verwendet (p<0,001). Im
Gegensatz dazu nutzten WB signifikant häufiger Zeitschriften (p=0,006) und
Hospitationen (p=0,024) im Vergleich zu den WBA für ihre Weiterbildung. Die
Einordung bestimmter chirurgischer Eingriffe im zeitlichen Verlauf der
Weiterbildung wurde von WBA und WB vergleichbar eingeschätzt. Sowohl die WBA,
als auch die WB waren mit der praktischen und theoretischen Ausbildung
größtenteils zufrieden. 61,1% der WBA und 57,1% der WB würden die Einführung
eines eigenständigen Facharztes für Handchirurgie begrüßen.
Fazit Die Bedeutung von digitalen Medien in der handchirurgischen
Weiterbildung wird zukünftig einen hohen Stellenwert einnehmen, weshalb digitale
Weiterbildungsangebote ausgebaut werden sollten. Es zeigte sich, dass sowohl die
WBA als auch die WB der Einführung des eigenständigen Facharztes für
Handchirurgie aufgeschlossen sind, was trotz der Verkürzung der
Weiterbildungszeit, die Kompetenz im Fachgebiet der Handchirurgie stärken
könnte.
Multiple Shunt Catheter Tips Migration into an Inguinal Hernia in an Adult
Authors: Alsheik Zuhdy , Margolin Emil , Robin Sharif , Dykman Daniel , Ezer Haim 
Published: September 2024

AbstractAlthough ventriculoperitoneal shunt tip migration into an inguinal hernia is considered common in children, while in adults it is quite rare. In fact, only a handful of cases have been reported in the literature. We report a rare case whereby two catheter tips (one from a lateral ventricle shunt and a second from a 4th ventricular shunt) migrated into an inguinal hernia. This migration caused distal shunt malfunction, and only distal catheter shortening and suturing to the abdominal wall caused the two shunts to function again.
Comparison of Effectiveness of Brivaracetam and Levetiracetam for Prophylaxis of Early Post-Traumatic Seizures: A Prospective Comparative Interventional Study
Authors: Pandya Rajan , Sundaram Ponraj Kamatchi , Baghel Shashank Singh 
Published: September 2024

Abstract
Introduction Early posttraumatic seizures (EPTS) are a major complication after a head injury, defined as seizures developing within the first 7 days of trauma. Levetiracetam has become a popular drug for the prevention of posttraumatic seizures in institutions worldwide. However, it has been reportedly associated with adverse effects like behavioral changes and somnolence. This study aimed to compare the efficacy of a newer drug, brivaracetam, which is reported to have a better pharmacokinetic profile. These findings may be significant in providing a safer yet efficacious alternative to levetiracetam.
Objective The aim of this study was to evaluate the efficacy of brivaracetam for prophylaxis of EPTS and to compare it with levetiracetam.
Materials and Methods A prospective, single-blind, parallel-group (alternate allocation) controlled trial over 100 patients admitted with traumatic brain injury in the Department of Neurosurgery, Goa Medical College, Panaji, Goa, India. The data was analyzed using IBM SPSS Statistics 29.0.
Results Twenty patients developed EPTS in the study group: 8 from the group receiving brivaracetam and 12 from the group receiving levetiracetam. Although the brivaracetam group had a lower incidence of EPTS, the difference was not statistically significant. Eleven patients from the levetiracetam group developed side effects, while six patients from the brivaracetam group had side effects. There was no significant difference in the incidence of side effects.
Conclusion Brivaracetam has efficacy equal to that of levetiracetam for prophylaxis of EPTS.