bluuebunny/crossref_metadata_2025 huggingface dataset:
A New Holistic Theoretical Framework to Inform Opioid Use Disorder Management
Authors: Coffee Zhanette , Taylor-Piliae Ruth , Badger Terry , Gordon Judith , Reed Pamela
Published: February 2025

Opioid use disorders (OUDs) are a public health crisis. Individuals with OUD often have coexisting symptoms: smoking, chronic pain, and anxiety. These coexisting symptoms increase the prevalence and severity of OUD. To inform OUD management, a new holistic theoretical framework (Complexity of Opioid Use Disorder Model [COUDM]) is proposed by combining two theories: Theory of Unpleasant Symptoms and Self-Determination Theory (SDT). TOUS and SDT comprehensively represent the complexity of the OUD experience, including influencing factors, interconnected conditions, and the motivation of individuals based on psychological needs that impact overall outcomes. Individuals receiving OUD treatment informed by SDT are more engaged and experience lower occurrences of drug relapse when they are intrinsically and autonomously motivated. COUDM encompasses the multidimensional aspects of OUD. To acquire a healthier and better future for OUD patients, novel frameworks to guide new approaches are needed. COUDM is a new theoretical framework, incorporating biopsychosocial factors and symptom clusters associated with OUD to improve treatment strategies.
“It Needs to Become a Norm Again and Not Make It Feel Like It’s Something so Foreign”: (Re)normalizing and Reclaiming Breastfeeding in African American Families
Authors: Woods Barr Alexis
Published: February 2025

Purpose:

To explore the lived experiences and perspectives of 3 generations of African American women regarding breastfeeding within their historical and cultural contexts, and to identify factors influencing their breastfeeding decisions and practices.

Background:

African American communities have a rich cultural heritage that includes infant nurturing. However, breastfeeding rates among African American mothers are comparatively low due to various societal factors, despite well-established health benefits. This disparity stems from historical trauma, socioeconomic inequities, and systemic barriers that disrupt community breastfeeding norms.

Methods:

This study presents a secondary analysis of data from an original qualitative study. Semi-structured interviews were conducted with 35 African American women from 15 family dyads/triads across 3 generations. Data were reexamined using deductive thematic analysis, allowing for emergent themes.

Results:

Six main themes emerged: intergenerational dynamics, tenacity/grit, self-empowerment, Blactivism, overcoming guilt, and a supportive breastfeeding ecosystem. These themes collectively form the framework of “(Re)Normalizing and Reclaiming Breastfeeding in African American Families,” highlighting patients’ resilience and agency in reclaiming breastfeeding practices.

Conclusions:

This study provides valuable insights into the complex factors influencing breastfeeding decisions and experiences among African American women. Findings underscore the importance of intergenerational support, self-empowerment, community activism, and a nurturing ecosystem in renormalizing breastfeeding within the African American community.

Implications:

Results can inform the development of culturally relevant interventions, policies, and support systems that promote breastfeeding equity and empowerment. Future research could focus on implementing and evaluating these strategies while addressing historical trauma and ongoing systemic barriers faced by African American women.
Urology Residency Program Directors’ Criteria for Evaluating Applicants
Authors: Bushweller Leila , Alvarez-Suarez Armando , Munoz-Lopez Carlos , Miranda Andre F. , Hudak Steven J. , Campbell Steven C. , DeWitt-Foy Molly E. , Han Justin S. , Nowacki Amy S. , Khouri Roger K.
Published: February 2025

Objective:

To evaluate how the recent changes to the urology residency application process affect program directors' (PD) criteria for evaluating applicants.

Methods:

All 148 urology PDs were invited to participate in an anonymous survey administered by REDCap in 2024.

Results:

Forty-eight of 148 PDs (32.4%) responded to the survey. When evaluating whether to interview an applicant, the highest ranked criterion of the 9 options listed was sub-internship (sub-I) performance at the PD’s institution, followed by letters of recommendation (LORs), preference signal (PS) sent to institution, and grades on surgery clerkships. The differences between these top 4 criteria were not statistically significant. Only 23% of PDs were likely to interview applicants who did not complete a sub-I with or send a PS to their program; 23% were neutral. However, 51% of PDs were likely to interview an applicant who sent them a PS, even if the applicant did not complete any sub-Is in their geographic region or send a geographic preference signal to their region; 31% were neutral. Only 21% of PDs were likely to interview applicants who did not submit a Step 2 score with their application; 44% were neutral.

Conclusions:

Sub-I performance is the most important factor for urology PDs, highlighting the importance of away rotations. LOR and PS continue to have a strong influence on interview invitations, but geographic signaling and geographic location of sub-Is do not. Having a Step 2 score at the time of application has become critical for many PDs. These findings will help guide future applicants in navigating the match.
Extracorporeal Membranous Oxygenation Associated With Tracheal Procedures: An Extracorporeal Life Support Organization (ELSO) Registry Analysis
Authors: Suzuki Yota , Christie Ian G. , Chan Ernest G. , Ryan John , Schuchert Matthew J. , Murray Holt N. , Furukawa Masashi , Sanchez Pablo G.
Published: February 2025

Extracorporeal membrane oxygenation (ECMO) has been primarily used for respiratory and circulatory failure, but its airway-related use has not been investigated well. Tracheal procedures are a situation when ECMO could be used to support patients during anticipated difficult airway management. The Extracorporeal Life Support Organization registry was queried for adult patients treated with ECMO in 2010–2022 during the same admission with types of tracheal procedures. Tracheal procedures were divided into surgical procedure and bronchoscopic procedure groups, and the survival rate was analyzed for each procedural type. Two-hundred sixty-nine patients met the inclusion criteria (64 surgical procedures and 205 bronchoscopic procedures), and 173 (64.3%) patients survived to discharge. Among the surgical procedures, tracheal resection was most performed (30 patients; 46.9%) and was associated with a high survival rate to discharge (86.7%; p = 0.003) compared with airway reconstruction (57.1%) and airway injury repair (46.2%). In bronchoscopic procedure, tracheal stent had favorable survival (76.1%; p = 0.004), whereas tumor debulking was associated with poor prognosis (48.3%; p = 0.006). Hemorrhagic complications were seen in 70 (26.0%) patients and were associated with a worse survival rate (58.6%; p < 0.001). Among them, surgical site bleeding was seen in 35 (13.0%) patients and was also associated with worse survival (42.9%; p = 0.007).
Stool Antigen Test for Helicobacter Pylori Infection in Adults
Authors: Silva Luz Marcel , Tianeze de Castro Caroline , Bueno Lemos Fabian Fellipe , Reis Rocha Gabriel , Lima Correa Santos Gabriel , Rocha Pinheiro Samuel Luca , de Oliveira Silva Luis Guilherme , Santos Calmon Mariana , Vasconcelos Oliveira Márcio , Teixeira Kádima Nayara , de Magalhães Queiroz Dulciene Maria , Freire de Melo Fabrício
Published: February 2025

Objective:

The stool antigen test (SAT) is a convenient noninvasive option for the diagnosis of Helicobacter pylori (H. pylori) infection. However, despite having been previously evaluated, there is currently a lack of evidence regarding the comparative accuracy of conventional and rapid SATs utilizing monoclonal or polyclonal antibodies in adults. Here, we perform a thorough statistical synthesis to determine and compare the diagnostic accuracy of conventional and rapid SATs for the diagnosis of H. pylori infection in adults.

Materials and Methods:

We conducted independent searches through July 25, 2023, for studies evaluating the accuracy of SAT against a reference standard. We assessed methodological quality using Quality Assessment of Diagnostic Accuracy Studies-2 and calculated overall accuracy measures using the bivariate random-effect model. We also conducted subgroup analyses based on model and assessment technique, and Spearman correlation analysis to investigate a possible threshold effect. We generated summary receiver operating characteristic curves to assess heterogeneity and evaluated publication bias.

Results:

Conventional SAT demonstrated superior sensitivity (92.19% vs 85.79%), specificity (92.93% vs 91.18%), likelihood ratios (LR+ 9.68 vs 8.16; LR- 0.10 vs 0.15), and area under the curve (0.958 vs 0.940) compared with rapid SAT. Notably, the diagnostic odds ratio for conventional SAT (114.70) significantly outperformed rapid SAT (diagnostic odds ratio: 57.72). Correlation analysis revealed no threshold effect and summary receiver operating characteristic curves showed consistent accuracy for both tests.

Conclusion:

Our study establishes evidence of the superior diagnostic accuracy of conventional SATs over rapid SATs for detecting H. pylori infection in adults. Also, we provide valuable insights into the impact of using monoclonal or polyclonal antibodies and different assessment techniques on diagnostic accuracy measures.
Accuracy of Single-dose Transcatheter Aortic Valve Replacement Planning CT Angiography for the Detection of Coronary Artery Disease
Authors: Gassert Florian T. , Brismar Torkel B. , Durukan Taha , Themudo Raquel , Svensson-Marcial Anders
Published: February 2025

Purpose:

To assess the accuracy of transaortic valve replacement (TAVR) planning CT examinations with a broad detector and a single dose of contrast media to diagnose CAD in a large patient cohort.

Materials and Methods:

In this retrospective study, consecutive patients who underwent a dedicated TAVR planning CT examination with a single contrast media dose and a 320-detector row between November 2017 and March 2021 were screened for inclusion. Inclusion criteria were a complete and correctly performed CT exam as well as an invasive coronary angiography (ICA). The scan consisted of 3 series: (1) ECG-triggered calcium score series over the heart. (2) ECG triggered i.v. CM scanning over the heart covering the entire cardiac cycle (0% to 100%). (3) non-ECG triggered scanning over the thoracic-abdominal area including subclavian and femoral arteries. For 2 and 3, a single i.v. CM bolus was used (300 mg iodine per kg total body weight of iodixanol, minimum 47 mL, maximum 75 mL at 100 kVp; 90 mL at 120 kVp). CT-derived CAD was defined as either free of obstructive CAD (<50%) or showing obstructive disease (>50%), further subclassified in moderate stenosis (50%–70%), or severe stenosis (>70%) for each vessel. ICA data were used as standard of reference.

Results:

We studied 599 patients (78.6±7.5 y, 358 men). In ICA, 428 of 2396 coronary vessels (17.8%) demonstrated stenosis of 50% or more. In a per-patient analysis, CTA had a sensitivity of 97.6% and specificity of 84.3% for the detection of patients with at least one vessel with stenosis of 50% or more as well as a NPV and PPV of 97.8% and 82.2%, respectively. In a per-vessel analysis, CTA had 80.8% sensitivity and 88.1% specificity for the detection of stenosis of 50% or more, as well as an NPV and PPV of 95.5% and 59.6%, respectively.

Conclusions:

Single-dose TAVR planning CT imaging with a wide detector has high sensitivity and NPV to exclude at least moderate CAD in TAVR candidates.
Hybrid Technique for Question Mark Ear Treatment
Authors: Chen Yongjun , Wei Siming , Hao Dongyue , Guo Yaotao , Ma Xianjie , Dong Liwei
Published: February 2025

The question mark ear is a rare external auricular deformity characterized by the cleft between the helix and earlobe. There is also limited guidance on the management of these deformities. A noteworthy aspect of the question mark ear is the broadening of the upper auricle, yet this feature can be easily overlooked. The hybrid technique, consisting of antihelix reformation, scapha reduction, and helical rim flap advancement, was proposed to correct the deformity and restore the natural appearance of the auricle. Auricular measurements, including the length and width of the auricle, the lateral circumference of the helix rim from the superior apex to the inferior apex, and the height of the cleft, were performed preoperatively and postoperatively. Fourteen patients with question mark ear deformities were treated, 11 unilaterally and 3 bilaterally. The patient’s ages ranged from 5 to 23 years old and 14.3 years on average. Follow-up ranged from 4 to 24 months and 10 months on average. Preoperative measurements indicated that the auricular width of the question mark ear was greater than that of the contralateral side, while postoperative measurements showed no significant difference in auricular width compared to the contralateral side. In addition, auricular measurements demonstrated a notable enhancement in the overall auricular configuration and cleft repair. The hybrid technique was applicable to correct question mark deformities with good results. The vertical mattress suture technique could reform the natural appearance of the antihelix. Scapha reduction and helical rim flap advancement were effective in correcting the cleft between the helix and earlobe.
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.
Chronic Graft-versus-host Disease, Part 2: Clinical Success and Roadmap to the Future
Authors: El Jurdi Najla , Blazar Bruce R. , Pavletic Steven Z.
Published: February 2025

Chronic graft-versus-host disease (cGVHD) is an immune-mediated, heterogeneous, multiorgan complication affecting allogeneic hematopoietic cell transplantation recipients, leading to increased morbidity, mortality, and decline in health-related quality-of-life. Advances in understanding the complex disease pathophysiology, and collaborative efforts lead by the National Institutes of Health to standardize criteria for clinical trials, led to bench-to-bedside efforts resulting in the development of 4 US Food and Drug Administration-approved agents for the treatment steroids-refractory cGVHD since 2017. Despite the remarkable advances in the field of hematopoietic cell transplantation in prevention of cGVHD, and more treatment options, the outcome of patients with moderate-severe cGVHD remains suboptimal. Essential to successful cGVHD management is to recognize the disease at early stages before the onset of irreversible damage, allowing for personalized multidisciplinary specialized interventions that include pharmacologic therapies and additional supportive care measures. The aim of this review is to summarize key areas of active clinical research and new developments in cGVHD therapeutic approaches, with focus on (1) preemptive therapy, (2) upfront therapy beyond corticosteroids, (3) treatment refractory cGVHD novel agents, role of combination therapies, and organ-specific approaches, and (4) challenges, gaps, and future directions.
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.
Tamlana flava sp. nov., isolated from mangrove sediment and genome-based taxonomic analysis of the genus Tamlana
Authors: Huang Zhaobin , Lai Qiliang , Dai Congjie
Published: February 2025

A novel yellow-coloured bacterial strain MA10T was isolated from mangrove sediment and subjected to polyphasic taxonomic identification. Strain MA10T was Gram-negative, rod-shaped, catalase-positive and oxidase-positive. Carotenoid pigment was present, and flexirubin-type pigment was absent. The 16S rRNA gene of strain MA10T had the highest sequence similarity with Tamlana crocina HST1-43T of 94.5%. The genome size was 3.77 Mbp with a genomic G+C content of 36.3%. The phylogenetic analysis of the 16S rRNA gene sequence and whole-genome sequence showed that strain MA10T belonged to the genus Tamlana of the family Flavobacteriaceae and tightly clustered with T. crocina HST1-43T. The digital DNA–DNA hybridization value and average nucleotide identity value between strain MA10T and T. crocina HST1-43T were 20.4 and 76.7%, respectively. The major menaquinone was MK-6. The major fatty acids (>10 %) were iso-C15:0 (41.6%) and iso-C15:1 G (16.8%). The polar lipids consisted of phosphatidylethanolamine, two unidentified aminolipids and three unidentified lipids. Based on the present polyphasic taxonomic study, strain MA10T was considered to represent a novel species of the genus Tamlana, for which the name Tamlana flava sp. nov. was proposed. The type strain was MA10T (=MCCC 1K09289T=KCTC 102321T). Additionally, the phylogeny of the 16S rRNA gene and whole-genome sequences found that the hitherto described nine species of the genus Tamlana and Algibacter onchidii presented polyphyletic clades, which could be divided into five different genera. The average amino acid identity value of 80% was chosen as the boundary of the five genera. Thus, except for the genus Tamlana, four novel genera named Allotamlana gen. nov., Cognatitamlana gen. nov., Neotamlana gen. nov. and Pseudotamlana gen. nov. were proposed. This study provided valuable taxonomic analysis of the genus Tamlana.
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

Fluorescence 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

Purpose

Explore 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.

Methods

We 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.

Results

The opioid overdose death rate trend was closely replicated by adding the social contagion component to our model.

Limitations

The 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.

Conclusions

Our 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.

Implications

Social 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

Background and Objective

Decisions 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).

Methods

Comprehensive 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 Limitations

AI 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 Implications

First 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 Summary

Our 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

Adolescence 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

Despite 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

Background

Endovascular 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.

Methods

OBPM 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.

Results

Eleven 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.

Conclusion

The 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 registration

URL: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

Background

There 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.

Objective

Our aim was to determine whether glucose circadian rhythm disruption is associated with preeclampsia and can be used to predict this pregnancy disorder.

Methods

We 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.

Results

71 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.

Conclusion

We 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

Under-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.
Continuous Outcome Estimation in N-of-1 Trials for Accelerated Decision-Making
Authors: Defelippe Victoria , Bartoš František , Wagenmakers Eric-Jan , Braun Kees P.J. , Jansen Floor E. , Otte Willem M.
Published: February 2025

N-of-1 trials aim to determine the therapeutic effect for a single individual. This individualized approach necessitates collecting multiple data points over time through repeated alternating periods of active treatment and a comparator or control condition. The extended duration of the treatment periods may increase patient burden, prolong placebo exposure, and increase the likelihood of study discontinuation. In theory, treatment responders (or non-responders) can be identified early during the trial if the therapeutic effect is strong (or completely lacking). There are no theoretical constraints to evaluate treatment efficacy more regularly – not only after a predetermined number of treatment periods – given that the individualized character of the N-of-1 study permits a statistical model update as soon as new data becomes accessible. Regularly updating estimates on treatment effects allows clinicians to accelerate clinical decision-making regarding N-of-1 study termination. This study examines the importance of continuous treatment effect estimation in N-of-1 trials through simulation and re-analysis of existing trial datasets of neurological diseases. Results indicate that treatment efficacy decisions can be expedited when outcome estimation is performed continuously rather than delayed until the end of the trial.
Associations between plasma proteins and psychological wellbeing: evidence from over 20 years of the English Longitudinal Study of Ageing
Authors: Gong Jessica , Scholes Shaun , Cole Steven , Zaninotto Paola , Steptoe Andrew
Published: February 2025

A deeper understanding of the molecular processes involved in psychological wellbeing in older adults is essential for advancing knowledge of underlying biological mechanisms. Leveraging proteomics data from 3,262 older adults (mean age=63.5 years, 55% female) of the English Longitudinal Study of Ageing (ELSA), we investigated the cross-sectional and longitudinal associations (before and after protein measurement) between 276 proteins and eudaimonic wellbeing, hedonic wellbeing, life satisfaction, and depressive symptoms, over 20-year span. For positive wellbeing, two proteins (DEFB4A and ECE1) were longitudinally associated with subsequent eudaimonic wellbeing trajectory. We further identified higher concentrations of 7, 8, and 2 proteins were linked to subsequent lower eudaimonic wellbeing, hedonic wellbeing, and life satisfaction, respectively. Sex differences in XCL1 and SLAMF7 were observed, associated with lower eudaimonic and hedonic wellbeing in males. These findings link human psychological wellbeing to regulation of several biological pathways, particularly involving cytokine regulation, neurotrophic signaling, inflammatory and immune systems.
Longitudinal evaluation of anti-SARS-CoV-2 neutralizing antibody levels in 3-dose homologous (mRNA-1273- mRNA-1273- BNT162b2) vaccinated Kidney transplant population: 18-month follow-up
Authors: Karunathilake Ridma P. , Kumara A , Karunathilaka A , Wazil AWM , Nanayakkara N , Bandara K , Abeysekera R , Noordeen F , Gawarammana IB , Ratnatunga Champa N.
Published: February 2025

Background

Kidney transplant recipients (KTRs) were given a 3-dose primary series of COVID-19 vaccination as they were vulnerable to infection due to immunosuppression.

Methods

This study was a longitudinal evaluation of nAB dynamics in 43 KTRs in a low-middle income setting receiving 3-dose homologous (mRNA-1273- mRNA-1273- BNT162b2) vaccination against COVID-19. Samples were obtained at time-points (TP) 0- pre-vaccination, TP1- 1 month post first dose(mRNA-1273), TP2-1-month post second dose (mRNA-1273), TP3- 4 months post-second dose, TP4- 2 weeks post-third dose(BNT162b2), TP5-5 months post-third dose and TP6-12 months-post third dose. Anti-SARS-CoV-2 nAB were detected using Genscript cPassTM pseudoviral neutralization kit. Demographic and clinical details were obtained through interviewer administered questionnaires.

Results

Pre-vaccination serum analysis showed n=7 KTRs had prior COVID-19 infection, classified as ‘infected+vaccinated,’ while others were ‘vaccinated. ‘ Both groups were similar in age(41.7years vs 46.7years,p=0.2383), gender, and transplant characteristics. Seroconversion and MAB in the vaccinated and infected+vaccinated KTRs were:TP1-8.3% vs 100%(p<0.001), MAB-64.3IU/ml vs 1424IU/ml(p=0.0167TP2-52.7% vs 100%(p=0.0194), MAB-175IU/ml vs 2790IU/ml(p<0.0001), TP3-100% vs 100%, MAB-106IU/ml vs 2153IU/ml(p=0.0002), TP4-100% vs 100%, MAB-736 IU/ml vs 2152IU/ml(p=0.0307) and TP6-100% vs 100%, MAB >2565IU/ml vs >3028IU/ml(p=0.5238) No factors were associated with seroconversion or MAB.

Conclusion

KTRs receiving a three-dose mRNA COVID-19 vaccine regime maintained strong nAB levels at one-year follow-up, with comparable antibody levels seen between KTRs with prior infection + vaccination and vaccination alone.
Semi-automated analysis of beading in degenerating axons
Authors: Pretheesh Kumar V C , Pullarkat Pramod
Published: February 2025

Axonal beading is a key morphological indicator of axonal degeneration, which plays a significant role in various neurodegenerative diseases and drug-induced neuropathies. Quantification of axonal susceptibility to beading using neuronal cell culture can be used as a facile assay to evaluate induced degenerative conditions, and thus aid in understanding mechanisms of beading and in drug development. Manual analysis of axonal beading for large datasets is labor-intensive and prone to subjectivity, limiting the reproducibility of results. To address these challenges, we developed a semi-automated Python-based tool to track axonal beading in time-lapse microscopy images. The software significantly reduces human effort by detecting the onset of axonal swelling. Our method is based on classical image processing techniques rather than an AI approach. This provides interpretable results while allowing the extraction of additional quantitative data, such as bead density, coarsening dynamics, and morphological changes over time. Comparison of results obtained through human analysis and the software shows strong agreement. The code can be easily extended to analyze diameter information of ridge-like structures in branched networks of rivers, road networks, blood vessels, etc.
Spectral preferences of mosquitos are altered by odors
Authors: Blake Adam J. , Riffell Jeffrey A.
Published: February 2025

Vision underlies many important behaviors in insects generally and in mosquitos specifically. Mosquito vision plays a role in predator avoidance, mate finding, oviposition, locating vertebrate hosts, and vectoring disease. Recent work has shown that when sensitized to CO2, the visual responses ofAedes aegyptiare wavelength-dependent, but little is known about how other olfactory stimuli can modulate visual responses. The visual cues associated with flowers, vertebrate hosts, or oviposition sites differs substantially and it is possible that odors might prime the mosquito visual system to respond to these different resources. To investigate the interplay of olfactory and visual cues, we adapted previously used wind tunnel bioassays to use quasi-monochromatic targets (390-740 nm) created with a novel LED synth. We coupled these visual targets with CO2 and the odors representative of vertebrate hosts, floral nectar or oviposition sites and assessed responses via 3D tracking of female mosquitos. When CO2 alone is present, we observe a lower preference for wavelengths in the green portion of the visible spectrum with a gradual increase as wavelengths moved towards the violet and red ends of the spectrum. However, when odors associated both with flowers and oviposition sites, we observed significant increases in mosquito preference for green (475-575 nm) stimuli. In contrast when vertebrate host odor was present, we saw increased preference for stimuli across the entire visible spectrum. These odor shifts in the mosquito spectral preferences suggest these preferences are not fixed and shift depending on behavioral context.