bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Vitamin D Level on The Prediction of The Success of Secondary Alveolar Cleft Grafting: A Retrospective Study
Authors: Fathy Abeer , Elhadidi Yasser Nabil , Gaber Ramy , Khairy Maggie A. , El Kassaby Marwa , Yehia Mahmoud 
Published: February 2025

Introduction:
Alveolar cleft grafting plays a vital role in the treatment of individuals with cleft lip and palate. Vitamin D plays a crucial role in bone healing.

Methodology:
The study involved 40 patients with cleft alveolus who were seeking alveolar cleft grafting (ACG). Participants were categorized into 2 groups—study and control—based on their vitamin D levels: those with levels below 20 were placed in the control group, while those with levels above 20 were assigned to the study group.

Results:
Assessment of alveolar cleft grafting success rate was done by Bergland Scale assessment. The assessment using χ2 showed that the bone level in the study group was better than the control. However, the improvement was not statistically significant (P=0.2). Assessment of volumetric bone fill was done on the CBCT. The results were statistically checked by independent t-test and showed that the bone fill in the study group (224±78.4 mm3) was better than the control (176±135 mm3). However, the improvement was not statistically significant (P=0.17). Assessment of the incidence of fistula recurrence was done using the χ2 test. In the study group, the incidence of fistula was 5%, while in the control group, it was 30%. The incidence of success in reducing fistula recurrence was statistically significant (P=0.04).

Conclusion:
Adjustment of vitamin D level may be a successful tool in predicting the success of the alveolar cleft grafting procedure, especially regarding the elimination of fistula recurrence.
Neoadjuvant Multiagent Systemic Therapy Approach to Liver Transplantation for Perihilar Cholangiocarcinoma
Authors: Soliman Nadine , Connor Ashton A. , Saharia Ashish , Kodali Sudha , Elaileh Ahmed , Patel Khush , Semaan Samar , Basra Tamneet , Victor David W. , Simon Caroline J. , Cheah Yee Lee , Hobeika Mark J. , Mobley Constance M. , Divatia Mukul , Dhingra Sadhna , Schwartz Mary , Maqsood Anaum , Heyne Kirk , Abdelrahim Maen , Javle Milind , Vauthey Jean-Nicolas , Gaber A. Osama , Ghobrial R. Mark 
Published: February 2025

Background.
Perihilar cholangiocarcinoma (phCCA) has excellent outcomes following liver transplantation (LT). Neoadjuvant radiation-based locoregional therapy is standard-of-care. Gemcitabine and cisplatin (gem/cis) combination systemic therapies have improved outcomes in advanced settings, but their efficacy pre-LT has not been studied.

Methods.
We review our experience following neoadjuvant gem/cis alone versus radiation-based approaches. Patients with phCCA undergoing LT at a single center between January 2008 and February 2023 were identified retrospectively. Neoadjuvant therapy was categorized as gem/cis systemic therapy (ST) alone, or any ST and radiotherapy (RT). Outcomes were posttransplant overall survival (OS), recurrence-free survival (RFS), waitlist time, and pathologic tumor response.

Results.
During study period, 27 phCCA patients underwent LT. One patient decompensated with neoadjuvant therapy and was excluded. Median age was 61 y (interquartile range, 53–68 y) and 14 (54%) were male. Of 26 patients, 12 (46%) received ST and 14 (54%) RT. Six RT patients received gem/cis ST. Median waitlist time was 199 d (interquartile range, 98–405 d) and did not differ by neoadjuvant regimen. Explanted tumors were predominantly T1 stage, without lymphovascular invasion or nodal involvement. Neither pathologic features nor percent tumor necrosis differed by regimen. OS probabilities at 1 and 3 y were 84% and 55% for the cohort. There was no significant difference in OS and RFS when stratified by regimen.

Conclusions.
Post-LT OS, RFS, waitlist time, and tumor response were similar in the 2 groups. Patients with phCCA who do not undergo RT may still be considered for LT under appropriate institution-based protocols that adhere to other established criteria.
Predicted Indirectly Recognizable T-cell Epitope (PIRCHE) Load Correlates With Rejection Events After Simultaneous Pancreas-Kidney Transplantation
Authors: Parajuli Sandesh , Niemann Matthias , Dale Bethany L. , Hidalgo Luis , Gupta Gaurav , Kaufman Dixon , Odorico Jon , Mandelbrot Didier 
Published: February 2025

Background.
Given the lack of specificity of current blood and urine testing and the resistance/inability to perform pancreas allograft biopsies, additional noninvasive investigational tools to assess the risk for rejection are needed. This study examines the clinical impact of molecular HLA matching in a large single-center simultaneous pancreas-kidney (SPK) transplant program.

Methods.
The study cohort comprised 238 SPK recipients between 2012 and 2021. The number of HLA mismatches, eplet, Snow (that counts the number of protein-specific surface-accessible donor HLA amino acid mismatches), and predicted indirectly recognizable T-cell epitope (PIRCHE, version 4.2; 100%) loads were calculated on the basis of 2-field HLA-A, -B, -C, -DRB1, and -DQB1 typing of recipients and donors. Univariable and multivariable Cox proportional hazard, as well as Kaplan-Meier analyses, were performed considering either first rejection events of a graft or a composite endpoint of de novo donor-specific antibodies, first rejection, and uncensored graft failure of either organ.

Results.
Kaplan-Meier analyses considered class II PIRCHE groups separated by a threshold of 7. From the considered histocompatibility metrics, multivariable regression analysis revealed only PIRCHE-II derived from donor HLA class II as statistically significantly correlated with clinical events and rejection after SPK, mostly driven by pancreas rejections. Furthermore, longer dialysis time and the induction agent had significant negative impacts on the defined composite endpoint.

Conclusions.
Our data support the clinical benefit of incorporating PIRCHE scores for the interpretation of class II HLA mismatches among patients undergoing SPK transplantation.
3D Tumor-Mimicking Phantom Models for Assessing NIR I/II Nanoparticles in Fluorescence-Guided Surgical Interventions
Authors: Harun Asma , Bendele Nathaniel , Khalil Mohammad Ibrahim , Vasquez Isabella , Djuanda Jonathan , Posey Robert , Christopher Gordon , Bickel Ulrich , Gruev Viktor , Tropp Joshua , Egan Paul F. , Srivastava Indrajit 
Published: February 2025

ABSTRACTFluorescence image-guided surgery (FIGS) offers high spatial resolution and real-time feedback but is limited by shallow tissue penetration and autofluorescence from current clinically approved fluorophores. The near-infrared (NIR) spectrum, specifically the NIR-I (700-900 nm) and NIR-II (950-1700 nm), addresses these limitations with deeper tissue penetration and improved signal-to-noise ratios. However, biological barriers and suboptimal optical performance under surgical conditions have hindered the clinical translation of NIR-I/II nanoprobes.In vivomouse models have shown promise, but these models do not replicate the complex optical scenarios encountered during real-world surgeries. Existing tissue-mimicking phantoms used to evaluate NIR-I/II imaging systems are useful but fall short when assessing nanoprobes in surgical environments. These phantoms often fail to replicate the tumor microenvironment, limiting their predictive assessment. To overcome these challenges, we propose developing tumor-mimicking phantom models (TMPs) that integrate key tumor features, such as tunable tumor cell densities,in vivo-like nanoparticle concentrations, biologically relevant factors (pH, enzymes), replicate light absorption components (hemoglobin), and light scattering components (intralipid). These TMPs enable more clinically relevant assessments of NIR-I/II nanoprobes, including optical tissue penetration profiling, tumor margin delineation, andex vivothoracic surgery on porcine lungs. The components of TMPs can be further modulated to closely match the optical profiles ofin vivoandex vivotumors. Additionally, 3D bioprinting technology facilitates a high-throughput platform for screening nanoprobes under realistic conditions. This approach will identify high-performing NIR-I/II probes with superior surgical utility, bridging the gap between preclinical findings and clinical applications, and ensuring results extend beyond traditionalin vivomouse studies.TOC
Evaluation and Replication of a Social Contagion Component of Opioid Use Disorder using Agent-Based Simulation Modeling
Authors: Bilden Rebecca C. , Kumar Praveen , Roberts Mark S. 
Published: February 2025

AbstractPurposeExplore the potential role of a social contagion factor of opioid use disorder by attempting to replicate the exponential rise in opioid overdose mortality rates using agent-based simulation modeling.MethodsWe utilized an agent-based simulation model built using the Framework for Reconstructing Epidemiological Dynamics software to implement the social contagion component. This updated model was run in Allegheny County for a 21-year period for this pilot study.ResultsThe opioid overdose death rate trend was closely replicated by adding the social contagion component to our model.LimitationsThe original model does not account for individual-specific risk factors. Furthermore, our model does not capture the effect of a social contagion on success in treatment.ConclusionsOur findings show that a social contagion component of opioid use disorder is potentially important in understanding the driving factors behind the exponential increase in opioid overdose death rates. There are likely other factors that are also partly responsible for these trends.ImplicationsSocial contagion could help explain the trends in opioid epidemic, but more research is warranted to understand its interaction with other factors, such as age, sex, race, opioid prescription rate etc.
Development of an artificial intelligence-generated, explainable treatment recommendation system for urothelial carcinoma and renal cell carcinoma to support multidisciplinary cancer conferences
Authors: Duwe Gregor , Mercier Dominique , Kauth Verena , Moench Kerstin , Rajashekar Vikas , Junker Markus , Dengel Andreas , Haferkamp Axel , Höfner Thomas 
Published: February 2025

AbstractBackground and ObjectiveDecisions on the best available treatment in clinical oncology are based on expert opinions in multidisciplinary cancer conferences (MCC). Artificial intelligence (AI) could increase evidence-based treatment by generating additional treatment recommendations (TR). We aimed to develop such an AI system for urothelial carcinoma (UC) and renal cell carcinoma (RCC).MethodsComprehensive data of patients with histologically confirmed UC and RCC who received MCC recommendations in the years 2015 – 2022 were transformed into machine readable representations. Development of a two-step process to train a classifier to mimic TR. Identification of superordinate categories of recommendations followed by specification of detailed TR. Machine learning (CatBoost, XGBoost, Random Forest) and deep learning (TabPFN, TabNet, SoftOrdering CNN, FCN) techniques were trained. Results were measured by F1-scores for accuracy weights. Additionally, clinical trial data for drugs were included.Key Findings and LimitationsAI training was performed with 1617 (UC) and 880 (RCC) MCC recommendations (77 and 76 patient input parameters). AI system generated fully automated TR with excellent F1-scores for UC (e.g. ‘Surgery’ 0.81, ‘Anti-cancer drug’ 0.83, ‘Gemcitabine/Cisplatin’ 0.88) and RCC (e.g. ‘Anti-cancer drug’ 0.92 ‘Nivolumab’ 0.78, ‘Pembrolizumab/Axitinib’ 0.89). Explainability is provided by clinical features and their importance score. TR and explainability were visualized on a dashboard. Main limitations: single-centre and retrospective study.Conclusions and Clinical ImplicationsFirst AI-generated explainable TR in UC and RCC with excellent performance results. Potential support tool for high-quality, evidence-based TR in MCC. Study sets global reference standards for AI development in MCC recommendations in clinical oncology.Patient SummaryOur artificial intelligence tool is designed to help experts at multidisciplinary cancer conferences make personalized treatment recommendations for each patient with urothelial or renal cell cancer. It was trained with extensive specific patient data and provides explanations of how recommendations were generated with good outcomes. Artificial intelligence can lead to improved treatment recommendations by providing a more comprehensive view of the individual patient in multidisciplinary decision making.
Age and Learning Shapes Sound Representations in Auditory Cortex During Adolescence
Authors: Benedikt Praegel , Feng Chen , Adria Dym , Amichai Lavi-Rudel , Shaul Druckmann , Adi Mizrahi 
Published: February 2025

SummaryAdolescence is a developmental period characterized by heightened plasticity, yet how ongoing development affects sensory processing and cognitive function is unclear. We investigated how adolescent (postnatal day 40 ± 2) and adult (postnatal day 80 ± 2) mice differ in performance on a pure tone Go/NoGo auditory discrimination task of varying difficulty. Using dense electrophysiological recordings, we measured spiking activity at single neuron resolution in the auditory cortex while mice were engaged in the task. Adolescent mice showed lower auditory discrimination performance compared to adults, particularly in more challenging versions of the discrimination. This performance difference was due to higher response variability and weaker cognitive control expressed as lower response bias. Adolescent and adult neuronal responses differed only slightly in representations of pure tones when measured outside the context of learning and the task. However, cortical representations after learning within the context of the task were markedly different. We found differences in stimulus- and choice-related activity at the single neuron level representations, as well as lower population-level decoding in adolescents. Overall, cortical decoding in adolescents was lower and slower, especially for difficult sound discrimination, reflecting immature cortical representations of sounds and choices. Notably, we found age-related differences, which were higher after learning, reflecting the combined impact of age and learning. Our findings highlight distinct neurophysiological and behavioral profiles in adolescence, underscoring the ongoing development of cognitive control mechanisms and cortical plasticity during this sensitive developmental period.
Structural Diversity of Metabotropic Glutamate Receptor/Beta-Arrestin Coupling
Authors: Marx Dagan C. , Gonzalez-Hernandez Alberto J. , Huynh Kevin , Strauss Alexa , Rico Carlos , Siepe Dirk , Gallo Pamela , Lee Joon , Sharghi Sheida , Arefin Anisul , Broichhagen Johannes , Eliezer David , Kalocsay Marian , Khelashvili George , Levitz Joshua 
Published: February 2025

AbstractDespite the widespread physiological roles of beta-arrestin (β-arr) coupling in G protein-coupled receptor (GPCR) regulation, the molecular basis of GPCR/β-arr interaction has been studied primarily in monomeric family A GPCRs. Here we take an integrative biophysical and structural approach to uncover extreme molecular diversity in β-arr coupling to the neuromodulatory metabotropic glutamate receptors (mGluRs), prototypical, dimeric family C GPCRs. Using a new single molecule pulldown assay, we find that mGluRs couple to β-arrs with a 2:1 or 2:2 stoichiometry via a combination of “tail” and “core” interactions. Single molecule FRET and electron microscopy show that β-arr1 stabilizes active conformations of mGluR8 and a combination of cryo-EM structures and molecular dynamics simulations define the positioning of mGluR8-bound β-arr1, together suggesting a steric mechanism of mGluR desensitization involving interactions with both subunits and the lipid bilayer. Finally, combinatorial mutagenesis enables the identification of a landscape of homo- and hetero-dimeric mGluR/β-arr complexes, including mGluR/β-arr1/β-arr2 megacomplexes, providing a framework for family C GPCR/β-arr coupling and expanding the known range of GPCR/transducer coupling modes.
Optical brain pulse monitoring of microvascular blood flow during endovascular treatment for acute ischemic stroke
Authors: Petautschnig Sigrid , Teo Elliot J , Sanders Lauren , Jhamb Ashu , Maingard Julian , Isik Finula I , Lee Jean , Dixon Barry 
Published: February 2025

AbstractBackgroundEndovascular treatment (EVT) of large vessel occlusion (LVO) strokes improves patient outcomes. However, significant challenges remain including detection of microvascular no reflow phenomena, emboli to new territories and improving neuro-prognostication. Real time monitoring of the brain microcirculation could assist in addressing these challenges. This first-in-human cohort study evaluated Optical Brain Pulse Monitoring (OBPM) of microvascular blood flow during EVT.MethodsOBPM is a non-invasive device using red and infrared light to capture brain pulse waveforms, reflecting the relative arteriole and venous pressure levels driving microvascular blood flow. OBPM brain pulse classes – Arterial, Hybrid, Venous I, Venous II and Monotonous – represent a continuum of blood flow states from normal (Arterial) to critically low blood flow (Monotonous). OBPM sensors were positioned bilaterally over the middle cerebral artery territories of LVO stroke patients undergoing EVT. Data on patient demographics, imaging and clinical outcomes were collected.ResultsEleven patients (mean age 71, NIHSS 13) were enrolled. The most common brain pulse class at presentation was the Venous I (64%). The brain pulse class at presentation was associated with the hypoperfused tissue volume (p = 0.005). The brain pulse class following EVT was associated with long-term patient outcomes, including length of hospital stay (p = 0.04), the modified Rankin Score (p = 0.06) and hospital death (p = 0.02). In one patient, OBPM detected an embolization to a new territory that occurred during internal carotid artery stenting.ConclusionThe OBPM brain pulse waveforms demonstrated venous circulation features in patients presenting with LVO stroke. These waveforms were also associated with clinical outcomes, such as stroke size at presentation, hospital LOS and mortality. Monitoring of the brain pulse during EVT could improve intra-procedural evaluation of microvascular no reflow, detection of complications and neuro-prognostication. OBPM also has potential as a simple method for earlier LVO stroke detection.Clinical trial registrationURL:https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=384769&isReview=true; Unique identifier: ACTRN12622001320741
Glucose Circadian Rhythm Disruption is Associated with Preeclampsia
Authors: Bravo R , Lee KH , Nazeer SA , Ashby Cornthwaite J , Sibai B , Fishel Bartal M , Pedroza C 
Published: February 2025

ABSTRACTBackgroundThere is emerging evidence of an association between circadian rhythms disruption and pregnancy complications. Preeclampsia is a leading cause of maternal death during pregnancy, and the role of circadian rhythms in predicting preeclampsia is not well understood.ObjectiveOur aim was to determine whether glucose circadian rhythm disruption is associated with preeclampsia and can be used to predict this pregnancy disorder.MethodsWe analyzed a dataset of 92 recruited individuals with Continuous Glucose Monitoring (CGM) data recorded at 24.62 (sd = 4.97) weeks of gestational age. To study rhythmicity, we performed a cosinor analysis using the packagescosinorandcosinor2, and we calculated the non-parametric circadian rhythm variables using thenparACTpackage in R. Furthermore, we performed multiple component cosinor analysis to detect internal oscillations and identify glucose postprandial peaks using the packageCosinorPyin Python.Results71 participants (20 women with preeclampsia) had sufficient data for studying glucose circadian rhythmicity and performing cosinor analysis for multiple components to detect the postprandial peaks. We found that all the participants exhibited a significant circadian rhythm in their glucose oscillation. We developed a model including the time difference between the first postprandial peak and the last one, L5 start-time (time at which the five consecutive hours with the lowest average glucose levels start) and age that was predictive for preeclampsia incidence (AUC: 0.80 95%CI: 0.69-0.91, specificity= 0.88, sensitivity = 0.37). Patients diagnoses with preeclampsia from this model had a reduced amplitude (p < 0.05) and less robust (p < 0.05) glucose rhythmicity.ConclusionWe conclude that evaluating glucose circadian rhythm during pregnancy may help to an earlier identification of preeclampsia.
Improving school age nutrition and school performance through amaranth plus flaxseed food product distribution in Sidama, Ethiopia: a study protocol
Authors: Orsango Alemselam Zebdewos , Dadhi Aberash Eifa , Tigistu Mekdes , Dinage Mehretu Belayneh , Engebretsen Ingunn Marie S. 
Published: February 2025

AbstractUnder-nutrition contributes to compromised learning, productivity and creativity in children. Primary school age children are a vulnerable group to under-nutrition, specifically anaemia and underweight. School feeding programs using locally grown foods targeting food insecure areas is one of the strategies to decrease the prevalence of under-nutrition in school children. Even if school feeding programs have been initiated in Ethiopia, the majority of vulnerable children have not benefitted from these interventions. Moreover, inadequate amount and poor quality of foods as well as sustainability of programs are challenging. Exploring underutilized and nutrient rich food sources could be one of the ways to mitigate the shortage of energy and nutrient dense food supplementation for school feeding. Amaranth is one of the few plants where leaves are eaten as a vegetable, while the seeds are used in the same way as cereals. In our previous work, we discovered that amaranth grain which grows as a wild plant has better nutrient content compared with the commonly consumed staple food maize. Also, an amaranth intervention done by this study group in younger children showed a significant effect on decreasing anaemia prevalence in children. But, we did not identify a significant weight or height change in the amaranth group. Further we found that the consumption of fish or seafood in the study area was almost null.This study aims to assess nutritional health and to reduce under-nutrition among school children by promoting amaranth plus flaxseed food from locally grown, standardised foods in Sidama, Ethiopia.Under this research project the following three study designs will be undertaken: a laboratory based food analysis study, a cross sectional study and an experimental pilot study.