bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel anti-HER2 monoclonal antibody IAH0968 in HER2-positive heavily pretreated solid tumors: results from a phase Ia/Ib first-in-human, open-label, single center study
Authors: Song Na , Teng Yuee , Shi Jing , Teng Zan , Jin Bo , Qu Jinglei , Zhang Lingyun , Yu Ping , Zhao Lei , Wang Jin , Li Aodi , Tong Linlin , Jiang Shujie , Liu Yang , Yin Liusong , Jiang Xiaoling , Xu Tie , Cui Jian , Qu Xiujuan , Liu Yunpeng 
Published: November 2024

BackgroundIAH0968 is an afucosylated anti-epidermal growth factor receptor 2 (HER2) monoclonal antibody which improved the activity of antibody-dependent cellular cytotoxicity (ADCC) and superior anti-tumor efficacy.MethodsTo determine the maximum tolerated dose (MTD) with dose-limiting toxicity (DLT), a single institution, phase Ia/Ib study was undertaken, using 3 + 3 design. The primary endpoints were safety, tolerability and preliminary clinical activity. Eighteen patients were evaluable for safety and fifteen patients were suitable for efficacy analysis. Dose escalations were 6 mg/kg (N = 2), 10 mg/kg (N = 7), 15 mg/kg (N = 5), and tolerable up to 20 mg/kg (N = 4).ResultsOnly one DLT was found at dosage 10 mg/kg, and no MTD was reached. The most common Grade 3 treatment-related adverse events (TRAEs) were hypokalemia (5.6%), supraventricular tachycardia (5.6%), interval extension of QTC (5.6%), and infusion reaction (5.6%). Grade 4 TRAE was arrhythmia (5.6%). No serious TRAE or Grade 5 was reported. 22.2% of patients had a TRAE leading to dose adjustment and 16.7% of patients had a TRAE resulting in discontinuation of IAH0968. After a median follow-up of 9.7 months (range, 3.7 - 22.0), the objective response rate (ORR) was 13.3% (2/15), the disease control rate (DCR) was 53.3% (8/15), and median progression-free survival (mPFS) was 4.2 months (95% CI: 1.4 - 7.7), and the median duration of disease control (DDC) was 6.3 months (95% CI: 2.9–not reached), with 4/15 responses ongoing.ConclusionsIn HER2-positive heavily pretreated metastatic patients, IAH0968 demonstrated promising clinical activity with durable responses and tolerable safety profiles.Clinical trial registrationClinicalTrials.gov, identifier NCT04934514.
Comparison of lenvatinib plus pembrolizumab versus first-line systemic chemotherapy for advanced intrahepatic cholangiocarcinoma: a real-world retrospective study
Authors: Yang Zhenyun , Wu Weijie , Hu Zhiwen , Fu Yizhen , Hu Zili , Pan Yangxun , Wang Juncheng , Chen Jinbin , Zhou Zhongguo , Zhang Yaojun , Chen Minshan , Hu Dandan 
Published: November 2024

BackgroundSystemic chemotherapy (SC) stands the only first-line treatment for advanced intrahepatic cholangiocarcinoma (iCCA) for the past few decades. Immune checkpoint inhibitors (ICIs) have been proved to provide additional benefit in disease control. However, oncological outcome of iCCA remains poor and awaits further improvement with new treatment modalities. Promising results have been observed in lenvatinib plus pembrolizumab (Len-P) as a second-line therapy in iCCA. This study aimed to explore the safety and efficacy of Len-P as a first-line therapy for iCCA patients in real-world clinical practice.MethodsWe retrospectively enrolled 133 patients with advanced iCCA who received Len-P or SC between May 2019 and May 2023. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were compared between the two groups.ResultsThere were 72 patients and 61 patients in the Len-P and SC groups, respectively. The median OS for the Len-P and SC groups was 16.3 and 17.8 months, respectively. The median PFS for the Len-P and SC groups was 8.9 and 11.4 months, respectively. There was no significant difference in ORR and DCR between the Len-P and SC groups (ORR: 22.2% vs. 23%; P=0.92; DCR: 69.4% vs. 77%; P=0.58). Additionally, the overall incidence of AEs was lower in the Len-P group than SC group. Low inflammation-based scores were indicative of favorable outcomes in patients undergoing Len-P therapy.ConclusionThis study demonstrated that Len-P is promising for the treatment of advanced ICC, with highly improved safety. It emerges as a viable treatment alternative for advanced iCCA. Inflammation-based scores show potential utility in identifying individuals likely to benefit from Len-P therapy.
The bidirectional relationship between subjective visual function and domain-specific cognition in cognitively unimpaired older adults and adults with mild cognitive impairment
Authors: Dubois Abigail , Sergio Jordan , Mozdbar Sima , Price Ashley , Stradtman Megan , Thompson Louisa I. , Snyder Peter J. , Alber Jessica 
Published: November 2024

IntroductionSubjective visual impairment (VI) is related to cognition in cognitively unimpaired (CU) older adults, mild cognitive impairment (MCI) patients, and Alzheimer’s disease (AD) patients. The utility of subjective VI as an indicator for domain-specific cognitive impairment is unknown.MethodsWe used the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25 item) and a neuropsychological battery to assess the relationship between subjective VI and domain-specific cognitive performance in CU older adults (N = 58) and MCI patients (N = 16).ResultsThe CU group showed a positive relationship between subjective VI and visuospatial performance. CU older adults at high risk for AD demonstrated a unique relationship between subjective VI and attention, processing speed, and executive function. Peripheral vision was related to domain-specific performance in the patient group.DiscussionSubjective VI complaints may indicate potential for domain-specific cognitive decline in visuospatial performance, executive function, processing speed, and attention in older adults.
Association between cardiometabolic index and biological aging in the US population: evidence from NHANES 2015–2020
Authors: Sun Miao , Bao Shuang 
Published: November 2024

PurposeIt is crucial to identify biomarkers that influence the aging process and associated health risks, given the growing severity of the global population aging issue. The objectives of our research were to evaluate cardiac metabolic index (CMI) as a novel biomarker for identifying individuals at increased risk of accelerated biological aging and to assess its use in guiding preventive strategies for aging-related health risks.MethodsThe National Health and Nutrition Examination Survey (NHANES) provided cross-sectional data on participants with complete information on CMI, phenotypic age (PA), and other variables. Analyses of variance and weighted χ2 tests were conducted to assess differences between groups. The relationship between CMI and biological aging was investigated using a weighted multivariate logistic regression model, restricted cubic spline (RCS) regression analysis, subgroup analysis, and interaction testing.ResultsA positive correlation between CMI and biological aging was observed in 6,272 participants. RCS regression analysis confirmed the non-linear relationship, identifying significant inflection point at 1.10. In the crude or adjusted models, the OR (95% CI), for the highest group versus the reference were 3.608 (3.108, 4.188), 3.397 (2.920, 3.952), and 1.550 (1.299, 1.850), respectively, when categorizing CMI into different groups. Subgroup analyses and interaction tests indicate that the association between CMI and biological aging remained consistent across different subgroups. Gender, race, education level, marital status, poverty income ratio (PIR), drinking status and diabetes had an interaction with CMI in relation to biological aging.ConclusionAn elevated CMI is linked to increased risk for biological aging. This relationship may inform more effective prevention and treatment strategies for biological aging in the future. CMI be integrated into routine health screenings or aging assessments by healthcare professionals.
Prognostic factors and surgical approaches in the analysis of primary central nervous system diffuse large B-cell lymphoma: a large population-based cohort study and external validation
Authors: Pan Zhibo , Huang Zhaoneng , Xing Zhenqiu , Yang Jianjing , Huang Shengwei , Zhang Yu 
Published: November 2024

IntroductionThis study aims to investigate prognostic indicators and assess surgical interventions’ impact on Primary central nervous system lymphoma-diffuse large B-cell lymphoma (PCNS-DLBCL) patients.MethodsA comprehensive examination was performed on a group of 3,962 cases in the Surveillance, Epidemiology, and End Results (SEER) database, as well as 27 cases of PCNS-DLBCL from the First Affiliated Hospital of Wenzhou Medical University. The application of both univariate and multivariate Cox regression analyses facilitated the identification of significant risk factors associated with PCNS-DLBCL. Developing and verifying nomograms, the reliability of the nomogram was evaluated by C-index, ROC curve, calibration curve and decision curve analysis. Finally, by using Kaplan–Meier (KM) curves to assess the survival rates for PCNS-DLBCL patients.ResultsAge, gender, marital status, tumor location, HIV infection status, chemotherapy, and surgical scopes emerged as independent prognostic factors for overall survival (OS) in multivariate Cox regression analysis, whereas gender did not demonstrate significance as a factor for cancer-specific survival (CSS). The C-index, calibration curves, ROC curves, and DCA curves demonstrating strong reliability and practicality. KM analysis revealed significantly improved OS and CSS in patients who underwent surgical resection compared to those who received no surgery/biopsy, especially receiving subtotal resection (STR). In addition, among patients receiving chemotherapy, both STR and gross total resection (GTR) improved survival time compared to chemotherapy alone, particularly with STR. In the non-chemotherapy group, GTR potentially improved CSS, there was no notable disparity in OS between patients who underwent surgery and those who did not or received biopsy.ConclusionThis study analyzed prognostic factors in PCNS-DLBCL patients, resulting in nomograms predicting 1-, 3-, and 5-year OS and CSS, which showed preferable performance. Combining different resection scopes with chemotherapy improved survival compared to chemotherapy alone, advocating for integrated treatment strategies. Surgery alone is not recommended based on our findings.
Cognition and behavior in adults with neurofibromatosis type 1
Authors: Bos-Roubos Anja , van Leeuwen Hanneke , Wingbermühle Ellen , van den Bosch Louisa , Ossewaarde Lindsey , Taal Walter , de Graaff Laura , Egger Jos 
Published: November 2024

BackgroundNeurofibromatosis Type 1 (NF1) is a congenital neurocutaneous disorder. As NF1 is incurable and presents with a wide range of physical and mental symptoms, knowledge of neurocognitive and behavioral functioning can be an important aid in understanding their functional impact, and developing treatment options. To date, studies in children with NF1 have shown dysfunction in several domains, but much less is known about cognition and behavior in adults with NF1. The present study describes the neuropsychological phenotype of adults with NF1 based on comprehensive clinical examination of cognition and behavior across multiple functions.MethodsParticipants were 62 adults with NF1 (mean age 38.2 years; SD 13.4). All underwent individual clinical neuropsychological assessment at the Center of Excellence for Neuropsychiatry as part of regular care. Scores on all individual measures were standardized into z-scores based on the corresponding normative group data. The proportions of mean z-scores in the NF1 study group were calculated according to cut-off points (±1 to ±1.5 SD; &gt; ±1.5 SD) and compared to the expected proportions in the normal population distribution. Cognition and behavior was tested against population means constructed by bootstrapping.ResultsPerformance on the cognitive measures oral reading speed, visuospatial copying, visuospatial immediate recall, visual learning/imprinting, and visual memory immediate recall in the NF1 group were lower than normative means. The behavioral measures indicated higher levels of dysfunction, including psychopathology. The proportions of the NF1 study group with lower cognitive performance and higher levels of behavioral dysfunction were larger than in the normal population distributions. In addition, domain-level results revealed that intelligence, attention/speed, memory, and social cognition reflect cognitive dysfunction. Moreover, levels of emotion perception problems, experienced executive dysfunction, internalizing psychopathology (e.g., anxiety, depression), and severe fatigue were significantly higher compared to the simulated population sample. The mean level of emotion regulation (coping strategies) did not differ significantly from the population.ConclusionIdentified cognitive and behavioral dysfunction in multiple domains indicates high vulnerability in adults with NF1 and underscores the importance of individualized neuropsychological assessment and treatment. Further research on the relationships between cognition and behavior (including fatigue) in NF1 is warranted.
Ephaptic conduction in tonic–clonic seizures
Authors: Rabinovitch Avinoam , Rabinovitch Revital , Smolik Ella , Biton Yaacov , Braunstein Doron 
Published: November 2024

ObjectivesElectroencephalograms (EEGs) or multi-unit activities (MUAs) of tonic–clonic seizures typically exhibit a distinct structure. After a preliminary phase (DC shift, spikes), the tonic phase is characterized by synchronized activity of numerous neurons, followed by the clonic phase, marked by a periodic sequence of spikes. However, the mechanisms underlying the transition from tonic to clonic phases remain poorly understood.MethodsWe employ a simple two-dimensional cellular automaton model to simulate seizure activity, specifically focusing on replicating the tonic–clonic transition. This model effectively illustrates the physical processes during the ictal phase and, more importantly, differentiates the roles of neurons’ activity, identifying their origin as either synaptic or ephaptic.ResultsOur model reveals an intriguing interaction between the synaptic and ephaptic modes of action potential wave conduction. By replicating the EEG and multi-unit activity (MUA) structure of a tonic–clonic seizure and comparing it with real MUA data, we validate the model’s underlying assumption: the transition from tonic to clonic phases is driven by a shift in dominance from synaptic to ephaptic conduction. During synaptic-mode control, neural conduction occurs through synaptic transmission involving chemical substances, while in the ephaptic mode, information transfer occurs through direct Ohmic conduction.SignificanceGaining a deeper understanding of the neuronal electrical conduction transitions during tonic–clonic seizures is crucial for improving the treatment of this debilitating condition.
Chronic post-dural puncture headache–a serious and underrated complication following lumbar puncture: a cohort study
Authors: Kraus Luisa Mona , Häni Levin , El Rahal Amir , Vasilikos Ioannis , Fariña Nuñez Mateo Tomas , Volz Florian , Urbach Horst , Lützen Niklas , Ulrich Christian , Beck Jürgen , Fung Christian 
Published: November 2024

BackgroundPost-dural puncture headache (PDPH) is still mostly regarded a minor complication after lumbar puncture. In the International Classification of Headache Disorders (ICHD)-3 headaches lasting longer than 14 days or persisting after epidural blood patch (EBP) are not even considered. We illustrate that there may be many patients with persisting headaches and a large disease burden.MethodsIn a retrospective, single center analysis from 04/2018 to 03/2022 we assessed patients with a dural puncture and orthostatic headache of &gt;14 days duration, resistant to one or more EBPs. Socioeconomic factors and individual patient history were assessed by a specifically designed questionnaire.ResultsWe included 30 patients with a mean age of 36.4 (±10.6) years. The median duration of acute inpatient care was 31 (Interquartile ratio (IQR) = 32) days and of sick leave 381 (IQR = 666.3) days. Patients consulted a median of 5 (IQR = 6.5) different physicians/ institutions due to chronic post-dural puncture headache (cPDPH). All patients reported major negative impact of cPDPH on their social and work life.ConclusionDespite long hospitalizations and a profound impairment of social and work lives cPDPH was neglected and underrated in all patients. We conclude that cPDPH needs to be considered and might be an underreported, severe condition which requires further prospective studies.
The population based cognitive testing in subjects with SARS-CoV-2 (POPCOV2) study: longitudinal investigation of remote cognitive and fatigue screening in PCR-positive cases and negative controls
Authors: von Etzdorf Alina , Harzen Maja , Heinrichs Hannah , Seifert Henning , Groiß Stefan J. , Balloff Carolin , Feldt Torsten , Jensen Björn-Erik Ole , Lüdde Tom , Bernhard Michael , Schnitzler Alfons , Goebels Klaus , Kraus Jörg , Meuth Sven G. , Elben Saskia , Albrecht Philipp 
Published: November 2024

BackgroundThe majority of people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) only show mild respiratory symptoms. However, some patients with SARS-CoV-2 display neurological symptoms. Data on the exact prevalence and course of cognitive symptoms are often limited to patient reported outcomes or studies recruited at specialized centers.MethodsFor this prospective, non-interventional population based POPCOV2 study, 156 subjects who performed SARS-CoV-2 testing in the Düsseldorf metropolitan area at public test centers between December 2020 and February 2022 were recruited by handouts. SARS-CoV-2-positive and negatively tested subjects were included within the first seven days after the PCR test results. Cognitive testing was performed at baseline during home quarantine and after 4–6 as well as 12–14 weeks of follow-up. Individuals were examined remotely by videocalls using the Symbol Digit Modalities Test (SDMT) and the Montreal Cognitive Assessment (MoCA) in addition to the Brief Fatigue Inventory (BFI) and the Beck Depression Inventory-Fast Screen (BDI-FS).ResultsAt baseline, the SARS-CoV-2-positive group presented with higher levels of fatigue in the BFI. In both the SARS-CoV-2-positive and SARS-CoV-2-negative groups, some subjects presented attention and memory deficits, defined as a z-score &lt; −1,65 on the SDMT or &lt; 26 points on the MoCA (SDMT: 22.9% in the positive and 8.8% in the negative group, p = 0.024; MoCA: 35.6% in the positive and 27.3% in the negative group, p = 0.313). MoCA and SDMT improved over time in both groups. For MoCA scores, a significant difference between the two groups was only seen at the first follow-up. SDMT z-scores did not differ at any time between the groups.ConclusionThese results support previous evidence that mild SARS-CoV-2 infections are associated with increased fatigue. However, we found relevant rates of cognitive impairment not only in the infected but also in the control group. This underlines the importance of including a control group in such investigations.
Does exercise enhance the benefits of nutritional support on the biochemical markers of nutrition, anthropometry, and body composition in hemodialysis patients? A systematic review
Authors: Kamalzadeh Yazdi Raheleh , Radkhah Nima , Ostadrahimi Alireza 
Published: November 2024

BackgroundExercise and nutritional support are effective strategies in hemodialysis patients who often face health issues like protein-energy wasting (PEW). Therefore, this study aimed to evaluate whether combining exercise with nutritional support offers additional benefits for anthropometry, body composition, and biochemical markers of nutrition in hemodialysis patients.MethodsThis systematic review searched databases, including PubMed, Scopus, and Web of Science, until 14 February 2024 to identify relevant randomized controlled trials. Following screening and data extraction, quality assessment was conducted using the revised Cochrane Risk of Bias tool (ROB2). The study was reported following PRISMA guidelines.ResultsSix studies comprising 199 male and female hemodialysis patients were included. These studies did not report any significant differences in anthropometry, body composition, and nutritional status between individuals who received an exercise program along with nutritional support and those who received only nutritional support.ConclusionThis systematic review suggests that the combination of exercise with nutritional support may not improve the positive effects of nutritional support on anthropometry, body composition, and nutritional status in hemodialysis patients. However, due to the low quality and significant heterogeneity among the existing studies, further research is required to draw definitive conclusions.Systematic review registrationPROSPERO (www.crd.york.ac.uk/prospero; registration no: CRD42024542613).
Commissioning a clinical proton pencil beam scanning beamline for pre-clinical ultra-high dose rate irradiations on a cyclotron-based system
Authors: Saini Jatinder , Erickson Danielle P. Johnson , Vander Stappen François , Ruth Matt , Cui Sunan , Gorman Vanessa , Rossomme Séverine , Cao Ning , Ford Eric C. , Meyer Juergen , Bloch Charles , Wong Tony , Grassberger Clemens , Rengan Ramesh , Zeng Jing , Schwarz Marco 
Published: November 2024

BackgroundThis manuscript describes modifications to a pencil beam scanning (PBS) proton gantry that enables ultra-high dose rates (UHDR) irradiation, including treatment planning and validation.MethodsBeamline modifications consisted of opening the energy slits and setting the degrader to pass-through mode to maximize the dose rate. A range shifter was inserted upstream from the isocenter to enlarge the spot size and make it rotationally symmetric. We measured the beamline transport efficiency and investigated the variation in output due to the recombination of charge in the dose monitoring chamber. The output calibration was performed through a parallel plate chamber (PPC05), and an intercomparison was performed for various detectors. The pre-clinical field for mice irradiation consisted of different dose levels to deliver uniform doses in transmission mode. The field dose rates were determined through log files while scripting in TPS was used to estimate PBS dose rates. The survival experiments consisted of irradiating the full pelvis of the mice at UHDR and conventional dose rates.ResultsThe spot size was constant with beam current and had a sigma of 8.5 mm at the isocenter. The beam output increased by 35% at 720 nA compared to 5.6 nA, primarily due to recombination in the dose-monitoring ion chambers. The Faraday Cup and PPC05 agreed within 2%, while other detectors were within 3% of FC for dose rates &lt;60 Gy/s. The pre-clinical fields’ PBS dose rate is above 45 Gy/sec for all voxels within the target volume. The average and PBS dose rates decrease as field size increases and approaches 40 Gy/s for a field size of 7x7 cm2. All UHDR arms showed better survival than the corresponding conventional dose rate arms.ConclusionsWe successfully modified a clinical system to perform UHDR pre-clinical experiments. As part of our pre-clinical experiments, we observed the FLASH effect concerning mice survival.