bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surrogacy of Recurrence-free Survival for Overall Survival as an Endpoint of Clinical Trials of Perioperative Adjuvant Therapy in Hepatobiliary-pancreatic Cancers
Authors: Imamura Taisuke , Ohgi Katsuhisa , Mori Keita , Ashida Ryo , Yamada Mihoko , Otsuka Shimpei , Uesaka Katsuhiko , Sugiura Teiichi 
Published: August 2023

Objective:
To assess the correlation between recurrence-free survival (RFS) and overall survival (OS) in the hepato-biliary-pancreatic (HBP) surgical setting in order to validate RFS as a surrogate endpoint.

Summary Background Data:
Reliable surrogate endpoints for OS are still limited in the field of HBP surgery.

Methods:
We analyzed patients who underwent curative resection for HBP disease (986 patients with pancreatic ductal adenocarcinoma [PDAC], 1168 with biliary tract cancer [BTC], 1043 with hepatocellular carcinoma [HCC], and 1071 with colorectal liver metastasis [CRLM]) from September 2002 to June 2022. We also conducted meta-analyses of randomized controlled trials of neoadjuvant or adjuvant therapy to validate the surrogacy in PDAC and BTC.

Results:
Correlation coefficients between RFS and OS were low for HCC (ρ = 0.67) and CRLM (ρ = 0.53) but strong for PDAC (ρ = 0.80) and BTC (ρ = 0.75). In a landmark analysis, the concordance rates between survival or death at 5 years postoperatively and the presence or absence of recurrence at each time point (1, 2, 3, and 4 y) were 50%, 70%, 74%, and 77% for PDAC and 54%, 67%, 73%, and 78% for BTC, respectively, both increasing and reaching a plateau at 3 years. In a meta-analysis, the correlation coefficients for the RFS hazard ratio and OS hazard ratio in PDAC and BTC were ρ = 0.88 (P < 0.001) and ρ = 0.87 (P < 0.001), respectively.

Conclusion:
Three-year RFS can be a reliable surrogate endpoint for OS in clinical trials of neoadjuvant or adjuvant therapy for PDAC and BTC.
The Association of Cannabis use After Discharge from Surgery with Opioid Consumption and Patient-Reported Outcomes
Authors: Bicket Mark C , Ladha Karim S , Boehnke Kevin F , Lai Yenling , Gunaseelan Vidhya , Waljee Jennifer F , Englesbe Michael , Brummett Chad M 
Published: August 2023

Objective:
Compare outcomes of patients using versus not using cannabis as a treatment for pain after discharge from surgery.

Summary Background Data:
Cannabis is increasingly available and is often taken by patients to relieve pain. However, it is unclear whether cannabis use for pain after surgery impacts opioid consumption and postoperative outcomes.

Methods:
Using Michigan Surgical Quality Collaborative registry data at 69 hospitals, we analyzed a cohort of patients undergoing sixteen procedure types between January 1, 2021, and October 31, 2021. The key exposure was cannabis use for pain after surgery. Outcomes included post-discharge opioid consumption (primary) and patient-reported outcomes of pain, satisfaction, quality of life and regret to undergo surgery (secondary).

Results:
Of 11,314 included patients (58% female, mean age 55.1 years), 581 (5.1%) reported using cannabis to treat pain after surgery. In adjusted models, patients who used cannabis consumed an additional 1.0 (95% CI 0.4 to 1.5) opioid pills after surgery. Patients who used cannabis were more likely to report moderate-to-severe surgical site pain at 1 week (aOR 1.7, 95% CI 1.4 to 2.1) and 1 month (aOR 2.1, 95% CI 1.7 to 2.7) after surgery. Patients who used cannabis were less likely to endorse high satisfaction (72.1% vs. 82.6%), best quality of life (46.7% vs. 63.0%), and no regret (87.6% vs. 92.7%) (all P<0.001).

Conclusions:
Patient-reported cannabis use to treat postoperative pain was associated with increased opioid consumption after discharge from surgery that was of clinically insignificant amounts, but worse pain and other postoperative patient-reported outcomes.
Association Between Emergency Medical Service Agency Volume and Mortality in Trauma Patients
Authors: Silver David S. , Sperry Jason L. , Beiriger Jamison , Lu Liling , Guyette Francis X. , Wisniewski Stephen , Moore Ernest E. , Schreiber Martin , Joseph Bellal , Wilson Chad T. , Cotton Bryan , Ostermayer Daniel , Fox Erin E. , Harbrecht Brian G. , Patel Mayur , Brown Joshua B. 
Published: August 2023

Objective:
Evaluate the association of annual trauma patient volume on outcomes for emergency medical services (EMS) agencies.

Summary Background Data:
Regionalization of trauma care saves lives. The underlying concept driving this is a volume-outcome relationship. EMS are the entry point to the trauma system, yet it is unknown if a volume-outcome relationship exists for EMS.

Methods:
Retrospective analysis of prospective cohort including eight trauma centers and 20 EMS air medical and metropolitan ground transport agencies. Patients 18-90 years old with injury severity scores >9 transported from scene were included. Patient and agency-level risk-adjusted regression determined the association between EMS agency trauma patient volume and mortality.

Results:
33,511 were included with a median EMS agency volume of 374 patients annually (IQR 90-580). Each 50-patient increase in EMS agency volume was associated with 5% decreased odds of 6-hour mortality (aOR 0.95; 95%CI 0.92-0.99, P=0.03) and 3% decreased odds of 24-hour mortality (aOR 0.97; 95%CI 0.95-0.99, P=0.04). Pre-specified subgroup analysis showed EMS agency volume was associated with reduced odds of mortality for patients with prehospital shock, requiring prehospital airway placement, undergoing air medical transport, and those with traumatic brain injury. Agency-level analysis demonstrated that high-volume (>374 patients/year) EMS agencies had a significantly lower risk-standardized 6-hour mortality rate than low-volume (<374 patients/year) EMS agencies (1.9% versus 4.8%, P<0.01).

Conclusions:
A higher volume of trauma patients transported at the EMS agency-level is associated with improved early survival. Further investigation of this volume-outcome relationship is necessary to leverage quality improvement, benchmarking, and educational initiatives.
Technical Variant Liver Transplant Utilization for Pediatric Recipients: Equal Graft Survival to Whole Liver Transplants and Promotion of Timely Transplantation Only When Performed at High-volume Centers
Authors: Stoltz Daniel J. , Gallo Amy E. , Lum Grant , Mendoza Julianne , Esquivel Carlos O. , Bonham Andrew 
Published: August 2023

Background.
Technical variant liver transplantation (TVLT) is a strategy to mitigate persistent pediatric waitlist mortality in the United States, although its implementation remains stagnant. This study investigated the relationship between TVLT utilization, transplant center volume, and graft survival.

Methods.
Pediatric liver transplant recipients from 2010 to 2020 (n = 5208) were analyzed using the Scientific Registry of Transplant Recipients database. Transplant centers were categorized according to the average number of pediatric liver transplants performed per year (high-volume, ≥5; low-volume, <5). Graft survival rates were compared using Kaplan-Meier curves and log-rank tests. Cox proportional hazards models were used to identify predictors of graft failure.

Results.
High-volume centers demonstrated equivalent whole liver transplant and TVLT graft survival (P = 0.057) and significantly improved TVLT graft survival compared with low-volume centers (P < 0.001). Transplantation at a low-volume center was significantly associated with graft failure (adjusted hazard ratio, 1.6; 95% confidence interval, 1.14-2.24; P = 0.007 in patients <12 y old and 1.8; 95% confidence interval, 1.13-2.87; P = 0.013 in patients ≥12 y old). A subset of high-volume centers with a significantly higher rate of TVLT use demonstrated a 23% reduction in waitlist mortality.

Conclusions.
Prompt transplantation with increased TVLT utilization at high-volume centers may reduce pediatric waitlist mortality without compromising graft survival.
The current clinical perception of myotonic dystrophy type 2
Authors: Kleefeld Felix , Schoser Benedikt 
Published: August 2023

Purpose of review
Myotonic dystrophy type 2 (DM2) is a genetic disorder belonging to the spectrum of myotonic dystrophies. DM2 is characterized by progressive muscle weakness, wasting and muscle pain (myalgia), but can also affect many other organ systems. In this review, we provide an updated overview on the research literature on DM2 with a focus on the management of multisystemic involvement and atypical clinical phenotypes.

Recent findings
Recent studies have focused on different aspects of multisystemic involvement. Early and severe cardiac involvement can occur in DM2 and needs to be managed appropriately. Diabetes has been shown to be more common in DM2 than in DM1, while a combination of symptoms (cataracts, myotonia, tremor) can be used to raise clinical suspicion and initiate genetic testing for DM2. Autoimmune disease has been shown to occur in up to one-third of DM2 patients, possibly due to altered immune pathways. New evidence also suggests a childhood-onset phenotype presenting with foot deformities.

Summary
The multisystemic aspects of the disease require a multidisciplinary approach for some patients, most likely even including state-of-the-art cardiac and brain imaging to detect and treat complications earlier. Of note, our concept of DM2 as an adult-onset disease is somewhat challenged by evidence suggesting a few pediatric DM2 patients and possibly anticipation, at least in some DM2 families. More studies, including larger cohorts, are needed to better understand this possible early-onset DM2 phenotype variant.
Pan-Neurofascin autoimmune nodopathy – a life-threatening, but reversible neuropathy
Authors: Appeltshauser Luise , Doppler Kathrin 
Published: August 2023

Purpose of reviewAutoimmune nodopathies are immune-mediated neuropathies associated with antibodies targeting the peripheral node of Ranvier. Recently, antibodies against all neurofascin-isoforms (pan-neurofascin) have been linked to a clinical phenotype distinct from previously described autoimmune nodopathies. Here, we aim at highlighting the molecular background and the red flags for diagnostic assessment and provide treatment and surveillance approaches for this new disease.Recent findingsNeurofascin-isoforms are located at different compartments of the node of Ranvier: Neurofascin-186 at the axonal nodal gap, and Neurofascin-155 at the terminal Schwann cell loops at the paranode. Pan-neurofascin antibodies recognize a common epitope on both isoforms and can access the node of Ranvier directly. Depending on their subclass profile, antibodies can induce direct structural disorganization and complement activation. Affected patients present with acute and immobilizing sensorimotor neuropathy, with cranial nerve involvement and long-term respiratory insufficiency. Early antibody-depleting therapy is crucial to avoid axonal damage, and remission is possible despite extended disease and high mortality. The antibody titer and serum neurofilament light chain levels can serve as biomarkers for diagnosis and therapy monitoring.SummaryPan-neurofascin-associated autoimmune nodopathies has unique molecular and clinical features. Testing should be considered in severe and prolonged Guillain-Barré-like phenotype.
Profiling an integrated network of cellular senescence and immune resilience measures in natural aging: a prospective multi-cohort study
Authors: Mitin Natalia , Entwistle Amy , Knecht Anne , Strum Susan L. , Ross Allison , Nyrop Kirsten , Muss Hyman B. , Tsygankov Denis , Raffaele Joseph M. 
Published: August 2023

AbstractBackgroundBiological aging begins decades before the onset of age-related clinical conditions and is mediated by both cellular senescence and declining adaptive immune function. These processes are functionally related with the rate of senescent cell accumulation dependent upon a balance between induction and immune clearance. We previously showed that biomarkers in these domains can identify patients at-risk of surgery-related adverse events. Here, we describe evidence of clinical relevance in early aging and metabolic phenotypes in a general adult population.MethodsWe enrolled a total of 482 participants (ages 25-90) into two prospective, cross-sectional healthy aging cohorts. Expression of biomarkers of adaptive immune function and cellular senescence (SapereX) was measured in CD3+ T cells isolated from peripheral blood.FindingsWe established a network of biomarkers of adaptive immune function that correlate with cellular senescence and associate with early aging phenotypes. SapereX immune components associated with a decrease in CD4+ T cells, an increase in cytotoxic CD8+ T cells, and a loss of CD8+ naïve T cells (Pearson correlation 0.3-0.6). These components also associated with a metric of immune resilience, an ability to withstand antigen challenge and inflammation. In contrast, SapereX components were only weakly associated with GlycanAge (Pearson correlation 0.03-0.15) and commonly used DNA methylation clocks (Pearson correlation 0-0.25). Finally, SapereX biomarkers, in particular p16, were associated with chronic inflammation and metabolic dysregulation.InterpretationMeasurement of SapereX biomarkers may capture essential elements of the relationship between cellular senescence and dysregulated adaptive immune function and may provide a benchmark for clinically relevant health decisions.
Microsoft Bing vs. Google Bard in Neurology: A Comparative Study of AI-Generated Patient Education Material
Authors: Nazir Talha , Ahmad Usman , Mal Madho , Rehman Mushhood Ur , Saeed Reeda , Kalia Junaid S. 
Published: August 2023

AbstractBackgroundPatient education is an essential component of healthcare, and artificial intelligence (AI) language models such as Google Bard and Microsoft Bing have the potential to improve information transmission and enhance patient care. However, it is crucial to evaluate the quality, accuracy, and understandability of the materials generated by these models before applying them in medical practice. This study aimed to assess and compare the quality of patient education materials produced by Google Bard and Microsoft Bing in response to questions related to neurological conditions.MethodsA cross-sectional study design was used to evaluate and compare the ability of Google Bard and Microsoft Bing to generate patient education materials. The study included the top ten prevalent neurological diseases based on WHO prevalence data. Ten board-certified neurologists and four neurology residents evaluated the responses generated by the models on six quality metrics. The scores for each model were compiled and averaged across all measures, and the significance of any observed variations was assessed using an independent t-test.ResultsGoogle Bard performed better than Microsoft Bing in all six-quality metrics, with an overall mean score of 79% and 69%, respectively. Google Bard outperformed Microsoft Bing in all measures for eight questions, while Microsoft Bing performed marginally better in terms of objectivity and clarity for the epilepsy query.ConclusionThis study showed that Google Bard performs better than Microsoft Bing in generating patient education materials for neurological diseases. However, healthcare professionals should take into account both AI models’ advantages and disadvantages when providing support for health information requirements. Future studies can help determine the underlying causes of these variations and guide cooperative initiatives to create more user-focused AI-generated patient education materials. Finally, researchers should consider the perception of patients regarding AI-generated patient education material and its impact on implementing these solutions in healthcare settings.
In vivomapping of the deep and superficial white matter connectivity in the chimpanzee brain
Authors: Chauvel Maëlig , Uszynski Ivy , Herlin Bastien , Popov Alexandros , Leprince Yann , Mangin Jean-François , Hopkins William D. , Poupon Cyril 
Published: August 2023

AbstractMapping the chimpanzee brain connectome, and comparing it to humans, is key to our understanding of similarities and differences in primate evolution that occurred after the split from their common ancestor around 6 million years ago. In contrast with macaque species brain studies, less studies have specifically addressed the structural connectivity of the chim-panzee brain and its comparison with the human brain. Most comparative studies in the liter-ature focus on the anatomy of the cortex and deep nuclei to evaluate how their morphometry and asymmetry differs from that of the human brain, and some studies have emerged concern-ing the study of brain connectivity between primates. In this work, we established a new white matter atlas of the deep and superficial white matter structural connectivity in chimpanzees. In vivo anatomical and diffusion weighted magnetic resonance imaging (MRI) data were collected on a 3 Tesla magnetic resonance imaging (MRI) system in 39 chimpanzees. These datasets were subsequently processed using a dedicated fiber clustering pipeline adapted to the chimpanzee brain enabling us to create two novel deep and superficial white matter connectivity atlases representative of the chimpanzee brain. These atlases provide the scientific community with an important and novel set of reference data for understanding the commonalities and differ-ences of the structural connectivity between the human and chimpanzee brains, which will contribute to a better understanding of the hominin brain evolution.
Neuronal tuning and population representations of shape and category in human visual cortex
Authors: Bougou Vasiliki , Vanhoyland Michaël , Bertrand Alexander , Van Paesschen Wim , Op De Beeck Hans , Janssen Peter , Theys Tom 
Published: August 2023

ABSTRACTObject recognition and categorization are essential cognitive processes which engage considerable neural resources in the human ventral visual stream. However, the tuning properties of human ventral stream neurons for object shape and category are virtually unknown. We performed the first large-scale recordings of spiking activity in human Lateral Occipital Complex in response to stimuli in which the shape dimension was dissociated from the category dimension. Consistent with studies in nonhuman primates, the neuronal representations were primarily shape-based, although we also observed category-like encoding for images of animals. Surprisingly, linear decoders could reliably classify stimulus category even in data sets that were entirely shape-based. In addition, many tuning curves showed an interaction between shape and category tuning. These results represent the first detailed study on shape and category coding at the neuronal level in the human ventral visual stream, furnishing essential evidence that reconciles human imaging and macaque single-cell studies.
Histone Lactylation Drives CD8 T Cell Metabolism and Function
Authors: Raychaudhuri Deblina , Singh Pratishtha , Hennessey Mercedes , Chakraborty Bidisha , Tannir Aminah J. , Trujillo-Ocampo Abel , Im Jin Seon , Goswami Sangeeta 
Published: August 2023

SummaryThe activation and functional differentiation of CD8 T cells are linked to metabolic pathways that result in the production of lactate. Lactylation is a lactate-derived histone post-translational modification (hPTM); however, the relevance of histone lactylation in the context of CD8 T cell activation and function is not known. Here, we show the enrichment of H3K18-lactylation (H3K18la) and H3K9-lactylation (H3K9la) in human and murine CD8 T cells which act as transcription initiators of key genes regulating CD8 T cell phenotype and function. Further, we note distinct impacts of H3K18la and H3K9la on CD8 T cell subsets linked to their specific metabolic profiles. Importantly, we demonstrate that modulation of H3K18la and H3K9la by targeting metabolic and epigenetic pathways regulates CD8 T cell effector function including anti-tumor immunity in preclinical models. Overall, our study uncovers the unique contributions of H3K18la and H3K9la in modulating CD8 T cell phenotype and function intricately associated with metabolic state.
Structural and functional vascular dysfunction within brain metastases is linked to pembrolizumab inefficacy
Authors: Kim Albert E. , Lou Kevin W. , Giobbie-Hurder Anita , Chang Ken , Gidwani Mishka , Hoebel Katharina , Patel Jay B. , Cleveland Mason C. , Singh Praveer , Bridge Christopher P. , Ahmed Syed Rakin , Bearce Benjamin A. , Liu William , Fuster-Garcia Elies , Lee Eudocia Q. , Lin Nancy U. , Overmoyer Beth , Wen Patrick Y. , Nayak Lakshmi , Cohen Justine V. , Dietrich Jorg , Eichler April , Heist Rebecca , Krop Ian , Lawrence Donald , Ligibel Jennifer , Tolaney Sara , Mayer Erica , Winer Eric , Perrino Carmen M. , Summers Elizabeth J. , Mahar Maura , Oh Kevin , Shih Helen A. , Cahill Daniel P. , Rosen Bruce R. , Yen Yi-Fen , Kalpathy-Cramer Jayashree , Martinez-Lage Maria , Sullivan Ryan J. , Brastianos Priscilla K. , Emblem Kyrre E. , Gerstner Elizabeth R. 
Published: August 2023

AbstractStructurally and functionally aberrant vasculature is a hallmark of tumor angiogenesis and treatment resistance. Given the synergistic link between aberrant tumor vasculature and immunosuppression, we analyzed perfusion MRI for 44 patients with brain metastases (BM) undergoing treatment with pembrolizumab. To date, vascular-immune communication, or the relationship between immune checkpoint inhibitor (ICI) efficacy and vascular architecture, has not been well-characterized in human imaging studies. We found that ICI-responsive BM possessed a structurally balanced vascular makeup, which was linked to improved vascular efficiency and an immune-stimulatory microenvironment. In contrast, ICI-resistant BM were characterized by a lack of immune cell infiltration and a highly aberrant vasculature dominated by large-caliber vessels. Peri-tumor region analysis revealed early functional changes predictive of ICI resistance before radiographic evidence on conventional MRI. This study was one of the largest functional imaging studies for BM and establishes a foundation for functional studies that illuminate the mechanisms linking patterns of vascular architecture with immunosuppression, as targeting these aspects of cancer biology may serve as the basis for future combination treatments.