bluuebunny/crossref_metadata_2025 huggingface dataset:
Nutritional Risk Index (NRI) predicts the clinical outcomes of patients with gastric cancer who received immune checkpoint inhibitors (PD-1/PD-L1)
Authors: Xu Yuehua , Zhang Limin , Huang Qi , Yin Zhidong , Zhang Wei
Published: January 2025

Numerous studies have consistently indicated a connection between the clinical results of individuals who receive immunotherapy and their nutritional condition. This study aims to evaluate the predictive capacity of the Nutritional Risk Index (NRI) in gastric cancer patients who are undergoing treatment with immune checkpoint inhibitors (ICIs). This study included a total of 146 individuals diagnosed with gastric cancer and received a combination of chemotherapy and immunotherapy using PD-1/PD-L1 inhibitors. The threshold was established by utilizing the receiver operating characteristic (ROC) curve. To analyze the clinical and pathological characteristics of the 2 groups, we performed Chi-square test or Fisher exact test. Univariate and multivariate analyses were performed to assess the factors influencing progression-free survival (PFS) and overall survival (OS) rates. Additionally, we developed nomograms to accurately predict the probability of 1- year and 3-year survival in these patients. According to the threshold, there were 38 (26.0%) patients in the low NRI category and 108 (74.0%) patients in the high NRI category. In the high NRI group, the median survival PFS was 32.50 months, while it was 11.77 months in the low NRI group. Likewise, the average survival OS in the 2 categories was 18.57 months compared to an indefinite duration. Individuals classified in the low NRI category encountered reduced PFS and OS, with a hazard ratio (HR) of 2.015 and 2.093 respectively, along with corresponding P-values of .009 and .006. The analysis of multiple variables showed that the number of platelets and TNM stage were separate factors that predicted both PFS and OS. Additionally, NRI was further recognized as a separate predictive factor for overall survival. The analysis of a specific subgroup revealed that individuals in the low NRI category experienced worse PFS and OS, especially within the group receiving ICIs. The C-index and the respective 95% CI of the nomograms to forecast the likelihood of PFS and OS survival were 0.646 (0.583–0.709) and 0.693 (0.635–0.751). NRI has the capability to forecast the clinical results of individuals who were diagnosed with gastric cancer and have received ICIs. This makes it a feasible biomarker for identifying patients who could benefit from ICIs.
Integrative Korean medicine for recurrent lumbar disc herniation after coronavirus disease vaccination: A case report and literature review
Authors: Koh Ah-Ra , Kim Hyun-Woo , Lee Young-Jin , Jo Hye-Jeong , Chae Go-Eun , Kim Dong-Woo , Ha In-Hyuk , Kim Doori
Published: January 2025

Rationale:

Many side effects have been associated with the coronavirus disease (COVID-19) vaccine. While most adverse events (AEs) are mild, serious adverse events are occasionally observed in the neurological and musculoskeletal systems. Nevertheless, articles reporting such serious adverse events after COVID-19 vaccination are limited, and only few case reports with detailed descriptions are available in the literature.

Patient concerns:

Herein, we report the case of a 41-year-old male office worker who developed symptoms of recurrent disc herniation 2 days after COVID-19 vaccination; the patient had no other factors that may have caused the recurrence of disc herniation, such as excessively vigorous activities, following vaccination.

Diagnoses:

Consequently, the patient was suspected of having cauda equina syndrome owing to recurrent lumbar disc herniation, and he underwent surgery.

Interventions:

The patient underwent integrative Korean medicine treatment, including acupuncture, pharmacopuncture, and Chuna manual therapy, for 8 months postoperatively.

Outcomes:

After treatment, the patient’s postoperative complications improved; the Numerical Rating Scale score changed from 5 to 1, and the Oswestry Disability Index score changed from 30 to 3. A literature review showed various cases of adverse events related to musculoskeletal inflammation or immune-mediated pathogenesis.

Lessons:

This paper confirmed the possibility that COVID vaccination is related to lumbar disc herniation recurrence and the possibility of integrative Korean medicine as an effective treatment option after lumbar disc herniation surgery.
How cesarean section rates can be reduced through an effective financial strategy: A protocol for systematic review
Authors: Sugiyo Dianita , Kyvernitakis Ioannis , Bahlmann Franz , Brüggmann Dörthe , Al Naimi Ammar
Published: January 2025

Background:

The incidence of cesarean section (c-section) has been increasing after the introduction of national health coverage. There is potential evidence that unnecessary c-sections can be reduced through an effective financial strategy, which would make it possible to increase health equity in the future. Consistent with global trends, the rate of c-section in Indonesia increased from 1.6% in 1991 to 17.6% in 2017, while the World Health Organization standard rate is 10% to 15%. This study aims to explore and analyze strategies to reduce c-section rates and to report evidence-based research on an effective financial strategy model for reducing these rates.

Methods:

We used a systematic review framework involving electronic databases including PubMed, ProQuest, and ScienceDirect. The following literature search terms were used: “cost-benefit analysis,” “universal health care,” “cost controls,” “health expenditures,” “out-of-pocket expenses,” “c-section,” and “abdominal delivery.” The Joanna Briggs Institute critical appraisal checklist was used to independently assess the methodological quality. The findings were compiled using a meta-aggregation approach to summarize quantitative analysis results potentially based on different methodologies.

Results:

Among 883 database records, 26 studies were retained for full-text review. C-section risk factors, the role of financial system evaluation, and the application of the clinical audit cycles with assessments using Robson classification were discussed in the included papers. Several studies highlighted the crucial function of evaluating reward reimbursement schemes, suggesting that decreased c-section rates and other maternal-neonatal outcomes should be used as indicators.

Discussion:

This study identified an evidence base that suggests using Robson classification in clinical audit cycles to reduce c-section rates and avoid unnecessary c-sections. The other proposals for decreasing the rate were mainly focused on financial and nonfinancial strategies applied nationally and locally in hospital settings.
The causal relationship between circulating inflammatory proteins and heart failure: A two-sample Mendelian randomization study
Authors: Wei Fangxiang , Rui Haomiao , Bian Rutao , Liu Shunyu
Published: January 2025

This study aims to explore the causal associations of 91 circulating inflammatory proteins with ischemic cardiomyopathy heart failure (ICM), dilated cardiomyopathy heart failure (DCM), and hypertrophic cardiomyopathy heart failure (HCM) to provide new ideas for the study of relevant heart failure mechanisms, adjunctive diagnosis and differentiation, and the clinical application of relevant drug targets. An analysis of the causal relationship between circulating inflammatory proteins and heart failure was conducted via inverse-variance weighted, weighted median estimator (WME), weighted mode (WM), and Mendelian randomization-Egger regression with Mendelian randomization. A Mendelian randomization analysis of 91 circulating inflammatory proteins revealed that natural killer cell receptor 2B4 levels, CXCL-6, fibroblast growth factor 5 levels, and interleukin-10 levels had positive causal relationships with ICM, whereas CX3CL-1, C-X-C motif chemokine 9 levels, interleukin-10 levels, leukemia inhibitory factor receptor levels, and signaling lymphocytic activation molecule levels had negative causal relationships; C-C motif chemokine 20 levels, C-X-C motif chemokine 5 levels, C-X-C motif chemokine 9 levels, fibroblast growth factor 5 levels, and oncostatin-M levels were positively correlated with DCM, whereas eukaryotic translation initiation factor 4E-binding protein 1 levels and Fms-related tyrosine kinase 3 ligand levels were negatively associated with DCM; and the CD40L receptor, Fms-related tyrosine kinase 3 ligand levels, hepatocyte growth factor levels, and sulfotransferase 1A1 levels were negatively associated with HCM. In this study, 9 of the 91 circulating inflammatory proteins were causally related to the ICM (4 positive, 5 negative), 7 were causally related to the DCM (5 positive, 2 negative), and 4 were causally related to the HCM (all negative). This study provides a theoretical foundation for the study of the relevant mechanisms of heart failure, clinical diagnosis, and treatment, as well as potential drug candidates closely related to heart failure.
Factors contributing to under-5 child mortality in Nigeria: A narrative review
Authors: Olawade David B. , Wada Ojima Z. , Aderinto Nicholas , Odetayo Aderonke , Adebisi Yusuff Adebayo , Esan Deborah Tolulope , Ling Jonathan
Published: January 2025

Despite repeated efforts by the Nigerian government and the international community, under-5 child mortality remains alarmingly high in Nigeria. This narrative review aims to reassess the key factors contributing to this persistent public health challenge. A comprehensive search of peer-reviewed articles and reports published in English was conducted to identify and synthesize data on the factors predisposing Nigerian children under 5 to mortality. The review identifies multiple interrelated contributors, including socioeconomic, sociocultural, and demographic factors, inadequate access to healthcare services, an under-resourced healthcare system, and a shortage of qualified healthcare professionals. The high burden of communicable and preventable diseases also plays a significant role in under-5 mortality. To address these issues, targeted interventions such as improving healthcare access, strengthening the health system, and reducing poverty are essential. The findings underscore the urgent need for a coordinated, multi-sectoral approach to effectively reduce under-5 mortality in Nigeria and improve the health outcomes of vulnerable children. Government, healthcare providers, and communities must work together to address these concerns so that all children can access the care they need to live and flourish.
Network pharmacology and molecular docking approach to explore the potential mechanisms of Xuefu Zhuyu Capsule in coronary heart disease
Authors: Qian He , Chen Bing-Bing , Zhang Min , Zeng San-Jin , Jia Zhuang-Zhuang , Wang Shuo , Gao Shan , Shi An-Hua , Xie Jing
Published: January 2025

Xuefu Zhuyu Capsule (XFZYC) plays a pivotal role in treating coronary heart disease (CHD) because of its potent clinical effects and fewer side effects. However, the possible pharmacological effect on CHD is limited. Thus, this research systematically analyzes XFZYC and CHD through network pharmacology technology. We identified 139 active compounds and 127 overlapped target genes in 11 herbs of XFZYC by using network pharmacology, and these 127 genes regulated the major signaling pathways related to CHD. The analysis of protein–protein interaction networks demonstrated that 30 important gene targets, such as interleukin-6, signal transducer and activator of transcription 3, protein kinase B1, mitogen activated protein kinases 3, cellular tumor antigen p53, vascular endothelial growth factor A, transcription factor p65, and proto-oncogene c-Fos, participated in the regulation of 79 major signaling pathways related to CHD. On this basis, we found that protein kinase B1, cellular tumor antigen p53, and transcription factor p65, which played a role in multiple regulatory pathways of the network, were also regulated by more than 3 compounds and expressed in at least 4 herbs. Molecular docking showed that XFZYC had a good binding potential with the overlapped protein targets. Gene Ontology enrichment analysis revealed that the active targets involved a various of biological process, cellular component, and molecular function, which included the key ones such as positive regulation of transcription from RNA polymerase II promoter, plasma membrane, and protein binding. T cell receptor signaling pathway, programmed death-ligand 1 expression and programmed death cell receptor-1 checkpoint pathway in cancer, FOXO signaling pathway, Ras signaling pathway, interleukin-17 signaling pathway, and VEGF signaling pathway, which were selected from Kyoto Encyclopedia of Genes and Genomes, were closely related to XFZYC in the treatment of CHD. XFZYC has a potential pharmacological effect on CHD, which provides the value for further study of XFZYC’s therapeutic effect on CHD.
Investigating the causal relationships between attention-deficit/hyperactivity disorder and autoimmune diseases: Evidence from Mendelian randomization study
Authors: Zhou Yidong , Jin Bowen , Qiao Kai
Published: January 2025

Attention-deficit/hyperactivity disorder (ADHD) and autoimmune diseases have been found to be correlated in the observational studies, but the causal relationships have not been fully investigated. Two-sample Mendelian randomization (MR) analysis was used to explore the causal relationships between ADHD and 8 autoimmune disorders (systemic lupus erythematosus, Crohn disease, ulcerative colitis, type 1 diabetes, rheumatoid arthritis, psoriasis, ankylosing spondylitis [AS], and multiple sclerosis) with the publicly available genome-wide association study data in the European populations. Inverse-variance weighted (IVW), weighted median, and MR-Egger were used to estimate the causal effects. Extensive sensitivity analyses were employed to validate the 3 assumptions of MR and robustness of the results. Multivariable MR (MVMR) analysis was used to evaluate the direct causal effects adjusting for the potential confounding factors. The potential mediators of the causal effects were explored through the 2-step MR mediation analysis. With the Bonferroni corrected threshold, the IVW results indicated that genetically determined higher risk of ADHD was significantly associated with increased risk of psoriasis (IVW OR: 1.29; 95% CI: 1.11–1.49, P = 6.3e−04), but not with other autoimmune disorders. The reverse MR didn’t find significant causal effects of autoimmune diseases on ADHD. MVMR analysis indicated that the significant causal effects of ADHD on psoriasis remained significant after accounting for obesity, alcohol drinking, depression, and biological sex, but became nonsignificant when adjusting for smoking. Further mediation analysis suggested smoking might partially mediate the causal effects of ADHD on psoriasis (mediated percentage: 11.16%, 95% CI: 1.54% to 20.77%, P = .023). There is a significant causal relationship between ADHD and psoriasis, but not with other autoimmune disorders. The causal effects might be mediate by smoking. Our findings suggested that early prevention and lifestyle changes (such as smoking cessation) might be helpful to reduce the risk of developing psoriasis for ADHD patients. Further investigations were warranted to explore the underlying mechanisms and the potential clinical applications.
Primary sclerosing cholangitis with PLKR and UGT1A1 mutation manifested as recurrent bile duct stones: A case report
Authors: Zhou Yijun , Shen Wei , Cui Yusheng , Li Yunjiang , Liu Hong , Bao Jianfeng , Jin Qiaofei
Published: January 2025

Rationale:

Primary sclerosing cholangitis (PSC) is characterized by idiopathic intra- and extrahepatic bile duct inflammation and biliary fibrotic changes. Recurrent bile duct stones due to PLKR and UGT1A1 mutation is an extremely rare complications of PSC.

Patient concerns:

A 26-year-old male patient complains a history of recurrent yellow skin and urine for over a year.

Diagnoses:

Following dynamic magnetic resonance cholangiopancreatography imaging, colonoscopic manifestation, liver biopsy and whole exome sequencing, the patient was finally diagnosed with PSC - ulcerative colitis with PLKR and UGT1A1 mutation.

Interventions:

Following resolution of the obstruction, a long-term regimen of 1000 mg/d ursodeoxycholic acid in combination with 10 mg/d obeticholic acid to improve cholestasis, 8 g/d colestyramine to facilitate adsorption of excess bile acids and 1.2 g/d rifaximin to prevent biliary tract infection were prescribed.

Outcomes:

The patient’s liver biochemical parameters have improved significantly. His condition is stable and has not undergone liver transplantation at this time.

Lessons:

Close and dynamic detection of the patient’s biliary ductal lesions play an important role in the diagnosis of PSC. In the event of relatively rare biliary complications, attention should be paid to the presence of gene mutation.
Recovery from inferior alveolar neurosensory changes after lower third molar extraction: A multicenter, retrospective study
Authors: Naruse Tomofumi , Suyama Koki , Fukushima Hiromasa , Nakamura Norio , Yamashita Kentaro , Furukawa Kohei , Morishita Kota , Rokutanda Satoshi , Yamada Tomohiro
Published: January 2025

Inferior alveolar (IA) neurosensory changes are complications that infrequently occur after third molar extraction. However, no adequate treatment has been established for IA neurosensory changes. The present study aimed to establish an effective treatment for IA neurosensory changes following lower third molar extraction. A total of 10,062 patients (12,776 teeth) who underwent lower third molar extractions were enrolled between April 2014 and June 2022. The medical records of the patients were reviewed, and relevant data were extracted. The prevalence of risk factors for recovery from IA neurosensory changes was analyzed. In total, 221 patients (224 teeth) developed IA neurosensory changes. Temporary and permanent IA neurosensory changes occurred in 1.75% and 0.71% of patients, respectively. The 1-, 3-, and 6-month cumulative recovery rates were 25.0%, 60.1%, and 71.1%, respectively. Univariate analysis revealed that age < 40 years (hazard ratio [HR], 2.02; P < .001), local anesthesia (HR, 1.45; P = .03), and postoperative administration of corticosteroids (HR, 1.63; P = .04) were significantly associated with high recovery rates. The cumulative recovery rate significantly improved with corticosteroid administration (P = .04). However, no significant differences were observed using the propensity score matching method. No significant differences were observed with or without vitamin B12 administration. These results suggest that postoperative administration of corticosteroids enables recovery from IA neurosensory changes after third molar extraction.
Addressing Late-arriving Surgeons in Support of First-case On-time Starts
Authors: Ida Jonathan B. , Schechter Jamie H. , Olmstead John , Menon Archana , Iafelice Mary Beth , Sawardekar Amod , Leavitt Olga , Lavin Jennifer M.
Published: January 2025

Introduction:

First-case on-time starts (FCOTS) is an established metric of perioperative efficiency, impacting global perioperative throughput. Late-arriving surgeons are a common cause of late operating room (OR) starts. This project reflects a quality improvement effort to reduce late surgeon arrivals by 30% for 24 months and improve FCOTS.

Methods:

A multidisciplinary perioperative leadership team developed clear expectations, including tracking, roles, review processes, and consequences. These were broadly communicated among stakeholders, and feedback was incorporated. A new same-day surgeon-to-surgeon feedback mechanism was instituted for late surgeon arrivals, allowing for surgeon feedback and reiteration of expectations. Results were prospectively tracked for 24 months before and following implementation.

Results:

Late surgeon arrivals decreased by 45%, from 23.6 to 13 per month for 24 months before and following implementation, respectively (P < 0.001). Balancing measures did not see increases for the same periods. FCOTS increased from 66% to 72% postimplementation (P < 0.001). Statistical process control P-charts demonstrated centerline shifts for both metrics.

Conclusions:

Development and communication of a clear framework of expectations, review, and consequences, with ongoing monitoring, clear performance expectations, and timely feedback, can reduce late surgeon arrival and improve FCOTS. Direct and timely communication provided immediate feedback to late surgeons and indicated reporting errors, providing more accurate data on late starts. Consistent policy enforcement is critical for credibility.
TMJ Metastasis: Evaluation of 3 Patients
Authors: Machoň Vladimír , Vlachopulos Vasilis , Michl Petr
Published: January 2025

Metastases of the articular process, temporomandibular joint (TMJ), are rare findings. Their frequency is around 5% of patients with metastatic involvement of the mandible. The most common primary tumor is adenocarcinoma of the lung in women and adenocarcinoma of the prostate in men. The authors present 3 patients with TMJ metastasis. These were metastasis of breast adenocarcinoma, prostate adenocarcinoma, and lung adenocarcinoma. TMJ metastases are rare but complicated to diagnose because their presence may be accompanied by symptoms typical of other TMJ diseases (discopathy, arthritis, osteoarthritis). However, the authors recommend the unequivocal exclusion of a metastatic process in cases where the patient has a positive cancer history and their complaints do not respond to usual therapy.
Lesion-Network Mapping of Post-Stroke Depressive Symptoms: Evidence from Two Prospective Ischemic Stroke Cohorts
Authors: Ríos Ana Sofía , Temuulen Uchralt , Khalil Ahmed , Villringer Kersten , Ali Huma Fatima , Akdeniz Asli , Grittner Ulrike , Becher Matthias , Rackoll Torsten , Nave Alexander Heinrich , Sperber Pia S. , Liman Thomas , Otte Christian , Endres Matthias , Kufner Anna
Published: January 2025

Background

Post-stroke depression (PSD) affects up to one-third of stroke survivors, significantly impacting rehabilitation success and quality of life. However, its underlying pathophysiology remains unclear.

Methods

We analyzed two independent, prospective ischemic stroke cohorts (PROSCIS-BNCT01363856and BAPTISeNCT01954797; total N=377) to identify brain regions and networks associated with depressive symptoms post-stroke. Lesion-symptom mapping (LSM) assessed associations between lesion location and depressive symptoms measured via the Center for Epidemiologic Studies Depression Scale (CES-D) up to 12 months post-stroke, while lesion network mapping (LNM) evaluated lesion connectivity with brain networks. We explored correlations between spatial similarity to the LNM-identified network and CES-D scores using linear regression models.

Results

LSM revealed no significant associations between lesion location and depressive symptoms. In contrast, LNM showed that lesion connectivity to brain regions—including the frontal pole, middle and inferior frontal gyri, inferior temporal gyrus, supramarginal gyrus, angular gyrus, frontal orbital cortex, and thalamus—correlated with CES-D scores (r=0.12, p=0.02). These regions overlapped with canonical resting-state networks, such as the frontoparietal (Dice coefficient [DC] = 0.28), salience (DC = 0.27), and default-mode networks (DC = 0.20), as well as a previously published depression circuit (DC = 0.43).

Conclusions

Lesion location alone was not associated with depressive symptoms post- stroke. However, lesion connectivity analysis revealed associations with brain networks, particularly the frontoparietal, salience, and default-mode networks, suggesting that disruption to these circuits may contribute to the development of PSD up to one-year post-stroke.
Different mechanisms link gain and loss of kinesin functions to axonal degeneration
Authors: Liew Yu-Ting , Voelzmann André , Owens Milli , Day Maureece , Cairns William , Jones Ella , Dajas-Bailador Federico , McCann Sophie , Murphy Thomas , Tortoishell Haydn , Parkin Jill , Bailey David M.D. , Landgraf Matthias , Prokop Andreas
Published: January 2025

Axons are the slender, often meter-long projections of neurons that form the biological cables wiring our bodies. Most of these delicate structures must survive for an organism’s lifetime, meaning up to a century in humans. Long-term maintenance and sustained functionality of axons requires motor protein-driven transport distributing life-sustaining materials and organelles to places of need. It seems therefore plausible that loss of motor function can cause axon degeneration; however, also gain-of-function conditions were linked to disorders including motor neuron disease or spastic paraplegia. To understand this phenomenon, we studied ∼40 genetic manipulations of motor proteins, cargo linkers and regulators of reactive oxygen species in one standardisedDrosophilaprimary neuron system. Using axonal microtubule bundle organisation as a relevant readout reflecting the state of axon integrity, we found that losses of Dynein heavy chain, KIF1A/Unc-104 and KIF5/Kinesin heavy chain (Khc) all cause bundle disintegration in the form of chaotically curled microtubules. Detailed functional studies of Khc and its adaptor proteins revealed that losses of mitochondrial or lysosomal transport cause ROS dyshomeostasis, which is a condition that inducing MT-curling in fly and mouse neurons alike. We find that hyper-activated Khc induces the same MT-curling phenotype, not through ROS but directly through enhanced mechanical forces. Studies with loss of Unc-104 and expression of an ALS-linked mutant form of the human Khc orthologue KIF5A suggest that the two mechanisms apply to motors beyond Khc. We discuss a model which can explain the surprising common outcome of both conditions and examine its relevance for understanding motor-linked neurodegeneration.
Human resources and healthcare infrastructure in Peru: A cross-sectional analysis from 2018 to 2024
Authors: Bellido-Boza Luciana , Villarreal-Zegarra David , Valdivia-Miranda Paul
Published: January 2025

Background

The healthcare challenges from 2018 to 2024 in Peru focused on resource distribution, infrastructure gaps, and the impact of public policies on equity.

Objective

To describe the variations in the spatial distribution of healthcare professionals and available infrastructure in Peru between 2018 and 2024.

Method

Our design is observational. The Electronic Information Transfer System of Health Service Provider Institutions (IPRESS) and IPRESS Management Units (SETI-IPRESS) database was used between 2018 and 2024. Our study conducted a spatial visual analysis and a multiple linear regression mode

Results

Our study reveals an increase in IPRESS reporting data to SETI IPRESS in Peru, resulting in an increase in reported coverage from 2,255 institutions in 2018 to 3,560 in 2024. Additionally, significant growth has been identified in the average number of total clinics, beds, psychologists, medical technologists, obstetricians, pharmacists, and assistants available within IPRESS between 2018 and 2024. However, the average number of nurses and dentists decreased. Furthermore, a concentration of medical resources and infrastructure is observed in specific geographical areas, such as the departments of Lima and Lambayeque.

Conclusions

This study highlights the importance of health policies and strategies that could increase the number of care centers and improve the quality and equity in the distribution of health resources throughout Peru.
Mesoscale landscaping of the TRIM protein family reveals a novel human condensatopathy
Authors: Singh Hari R. , Sharma Vineeta , Nijssen Jik , Pozniakovski Andrei , Rubin Alexander , Liang Lorrin , Ball David , Hong Sunwoo , Gauntner Victoria , Yu Guanghao , Ranga Arathi , Salant David , Hildebrandt Friedhelm , Hyman Anthony A. , Majmundar Amar J.
Published: January 2025

The mesoscale organization of cells is central to cellular physiology and pathology. Cellular condensates often form via biomolecular phase separation, mediated by intrinsically disordered regions (IDRs) and represent a key mechanism for mesoscale organization. The TRI-partite Motif (TRIM) family of ubiquitin ligases is implicated in diverse cellular functions and disease, yet the role of biomolecular condensation in TRIM family organization remains understudied. Here, we systematically investigate the mesoscale localization of 72 TRIM proteins, revealing that a majority form condensates in distinct cellular compartments. IDR content correlates with dynamic condensate formation, suggesting a critical role in mesoscale organization. Focusing on TRIM8, associated with a neuro-renal disorder, we demonstrate that disease-causing truncations of the TRIM8 C-terminal IDR result in acondensatopathy, characterized by disrupted condensation, proteasomal regulation, and TAK1/NFκB signaling. Functional assays in cellular and animal models link these disruptions to podocyte dysfunction and impaired response to injury. Our findings establish a framework for understandingcondensatopathiesand the mesoscale principles governing TRIM family organization and function.
Untangling the Evolutionary Dynamics of the Phenome in Megadiverse Hymenoptera
Authors: Porto Diego S. , Vilhelmsen Lars , Mikó István , Tarasov Sergei
Published: January 2025

Hymenoptera is a megadiverse insect order, yet the drivers of its massive radiation remain poorly understood. Here, we employ novel comparative phylogenetic methods that integrate computational ontologies with ancestral state reconstructions of 346 discrete morphological characters to investigate the tempo and mode of phenome evolution in Hymenoptera across both adults and larvae. We examine the interplay between phenotypic rates, selection, modularity, and lineage diversification over deep time. Our analyses reveal that both larval and adult phenomes experienced an early burst scenario during the Late Permian - Triassic. However, their evolution appears decoupled, which enhanced the overall evolvability of Hymenoptera. Moreover, major phenotypic transitions in the order are complex, multifaceted processes driven by directional selection. One such event---the emergence of the wasp waist---involved a fundamental reorganization of the adult phenome. This dramatic transformation shifted net diversification from negative to positive during the Triassic, thereby enabling the subsequent survival and explosive diversification of the apocritan lineage.
Communication and teamwork between dental surgeons and dental technologists during fabrication of removable complete dentures in Makerere University Dental Hospital: a qualitative research study
Authors: Nono David , Bagenda Godfrey , Okullo Isaac , Rwenyonyi Charles Mugisha
Published: January 2025

Background and Objective

Edentulous patients seek services from dental professionals to replace lost teeth with removable complete dentures (RCDs). The dentist (dental surgeon) and dental technologists are expected to work as a team to fulfill all the expectations of the patient. Effective communication between the dentist and the technologist is important in ensuring that dentures are well-fabricated and fitted, and it also impacts the working relationship between the two professionals. The present study explored communication and teamwork between dental surgeons and dental technologists during the fabrication of RCDs.

Design

The study employed a qualitative design to explore communication and teamwork between dental surgeons and dental technologists. It was conducted using in-depth interviews of dental surgeons and technologists guided by data saturation.

Setting

The study was conducted in Makerere University Dental Hospital in Kampala, Uganda.

Participants

Twenty five participants: 13 dental surgeons and 12 dental technologists were interviewed during data collection.

Results

Generally, participants reported having a good working relationship, where they closely worked together and supported each other to ensure that patients are satisfied with RCD services. The dental surgeons and technologists used different forms of communication. However, the common form of communication was through the use of dental laboratory request forms on which all details about the procedures and materials were provided by the dental surgeons to dental technologists. To complement the dental laboratory request forms, the use of phone calls and electronic media like WhatsApp messages were equally important in emphasizing instructions and follow-ups to ensure that the work was well executed.

Conclusion

Most of the participants reported having a good working relationship aimed at offering the best services to the patients. Communication between the dental surgeons and dental technologists was mainly through the use of dental laboratory request forms. Phone calls and electronic media were equally important in emphasizing instructions and follow-ups to ensure that the work was well executed.

Strengths and Limitations of this study

◆

The strength of the present study was that it provided baseline data on communication and teamwork between dental surgeons and dental technologists, and how best they can be improved.

◆

The study limitations were that the participants were limited to general dental practitioners and no dental consultants were interviewed who probably could have different views. It was also conducted at one site (Makerere University Dental Hospital), which renders the findings to be generalized with caution.
Undergraduate GPA does not predict success in PhD programs for cohorts of MS students at two minority-serving institutions
Authors: Fuse M , Rath K , Riggs B , Esquerra RM , Peterfreund A , Gutierrez C , Bayliss F
Published: January 2025

Master of Science (MS) research training programs funded by organizations such as the NIH, the NSF as well as private corporations represent the potential for significant interventions for student success, especially for marginalized or underrepresented and first-generation students, to bridge the gap between undergraduate studies and doctoral programs. These students often face serious challenges during their undergraduate years, such as navigating unfamiliar academic systems, balancing demanding coursework with work responsibilities, and fulfilling family obligations. These and other systemic pressures can impede their academic progress and opportunities for research experience. We therefore asked how their undergraduate GPA impacted success in the PhD in terms of (i) acceptance, (ii) completion, and (iii) time to degree after participating in a funded MS research training program. We examined data collected at San Francisco State University and California State University, Los Angeles over a 30-year period because they (i) had similar student demographics, (ii) were institutions with strong MS degrees, and (iii) had an infrastructure (established offices) to coordinate various training programs. We found that high GPA did not predict greater success in entering or completing the PhD, or in time to degree. This study, therefore, demonstrates that undergraduates from diverse groups with lower undergraduate GPA levels can benefit from a structured MS research training program in reaching their goal of becoming a PhD scientist. Moreover, it indicates that more holistic approaches in admissions are required, including limiting the use of a GPA below 3.0 as an early filter to eliminate applicants. These MS programs appear to play a crucial role as a bridge to PhD studies and are instrumental in enhancing diversity within STEM fields. We suggest that a strategy for success is to provide infrastructure in the form of a coordinated office housing the training grants as a means of structuring mentorship and professional development for under-represented and first generation students.
Transcriptomic Profiling of Old Age Sarcoma Patients using TCGA RNA-seq data
Authors: Nagarajan Vidhyavathy , Karandikar Shreya S. , Dhevanayagam Mary S.J.
Published: January 2025

Sarcoma is a rare malignancy with poor prognosis, especially in older patients (≥ 65 years) as seen in our preliminary analysis and some previous studies. Moreover, these patients have limited treatment options due to therapy-associated adverse effects and altered tumor micro-environment, which could be associated with their lower prognosis. Studying the underlying biology that drives cancer progression in these patients will help design personalized therapy and improve outcomes for them. This study aims to analyze TCGA-SARC RNA-seq data for characterizing the transcriptomic profile of older age (OA: ≥ 65 years) compared to younger age (YA: 18-65 years) sarcoma patients. RNA-seq and clinical data of sarcoma patients were acquired from TCGA, and the samples were grouped as OA (≥ 65 years) and YA (18-65 years) patients. Differential gene expression analysis, pathway analysis, transcription factor enrichment analysis, gene-specific survival analysis and network analysis were performed. When comparing the gene expression profiles of the 108 OA and 154 YA patients, significant differentially regulated genes (n=733), transcription factors (n=10), hub genes (n=10) and the pathways that characterize the former were identified. Furthermore, 16 dysregulated genes were found that were significantly associated with a poor prognosis in OA sarcoma patients. In accordance with existing evidence of an altered tumor microenvironment in older-age cancer patients, the identified significant genes are associated with the regulation of certain important tumorigenic pathways such as EMT (epithelial-to-mesenchymal transition), calcium signaling, angiogenesis, ECM (extracellular matrix) degradation, Wnt/β-catenin pathways, suggesting the potential cause for lower prognosis in the OA patients. Thus, these findings pave the way to characterize the OA sarcoma patients which can be validated by multi-omics analysis and clinical studies in the future, in turn providing improved treatment options and survival for the same.
Biopolymers can be used for consolidation of lunar and Martian regoliths
Authors: Gupta Nitin , Kumar Aloke , Viswanathan Koushik
Published: January 2025

Creating long-term extraterrestrial habitats to support continuous human occupation requires structures that can bear load, while remaining resilient to large temperature fluctuations. Exploiting locally available regolith is part of a paradigm termedin situresource utilization (ISRU) that advocates minimal dependence on terrestrial supplies via local resource exploitation for construction. In this work, we report on a consolidation method for making load-bearing structures out of lunar and Martian regolith simulants using biopolymer binders. We quantify the compressive and tensile strength of the final brick-like structures, termed biopolymer regolith composites, and investigate their dependence on biopolymer concentration and chemistry. A pressure-assisted die casting process is developed that can produce bricks with compressive strengths of ∼ 15 MPa and tensile strengths of around 2 MPa, from regolith simulants. We finally report on the performance of these bricks under large temperature and pressure variations and find that their strengths remain unchanged. We believe that this makes biopolymer regolith composite bricks suitable candidates for use in harsh extraterrestrial environments, while adhering to the guidelines of the ISRU paradigm.

Keyword:Lunar regolith; Martian regolith; Space habitation; Extraterrestrial construction; Biopolymers; Regolith simulant
Value of chest Computed Tomography imaging radiomics features in predicting breast density classification
Authors: Zhou Weipeng , Yang Qi , Zhang Huimao
Published: January 2025

Objective: To explore the correlation between the radiomic characteristics derived from chest CT scan imaging and breast density classification, to construct an imaging radiomics model that can automatically achieve CT breast density classification, and to evaluate its diagnostic efficacy, so as to provide a valuable reference for breast density AI classification through chest CT scanning images. Methods: 393 patients who had negative results of breast ultrasound and mammography in our hospital and had undergone CT scanning of the chest within one year were collected for retrospective analysis, and 330 patients who had consistent results of breast density classification judged by two radiologists based on mammography images were used for the construction of imaging radiomics prediction models, which involved mapping of three-dimensional regions of interest (ROI) of the breast, extraction of imaging radiomics features and dimensionality reduction, screening of dominant radiomics features, establishment of multiple four-classification prediction models, and evaluation the effectiveness of each model. Results: A U-net neural network segmentation model was trained to automatically delineate breast ROI, extract 1427 radiomics features, and screen out 28 dominant features closely related to breast density for AI automatic classification of breast density. Among the four types of four-classification prediction models constructed based on classifier including ?Xgboost Classifier, ?One Vs Rest Classifier(Logistic Regression in the One Vs Rest framework), ?Gradient Boosting, ?Random Forest Classifier, Xgboost four-classification prediction model has the best prediction performance, and after its parameter tuning, the classification accuracy for the test set reaches 0.866, and the area beneath the curve (AUC) derived from the receiver operating characteristic curves (ROC) of the four categories of classification labels are 1.00, 0.93, 0.93,and 0.99, respectively, and the AUC of the micro-averaged ROC of each classification label is 0.97, and the AUC of the macro-averaged ROC is 0.96, indicating the best prediction performance. Conclusion: Chest CT plain images can provide breast density classification, a valuable information that reveal significant insights pertaining to breast cancer risk, and can be used to automatically achieve breast density four-classification through imaging radiomics model, which lays the foundation for precise and individualized breast screening programs. Introducing AI methods for automatic breast density classification can help clinical diagnosis.
Deciphering Functional Heterogeneity of Cancer-Associated Fibroblasts Across Molecular Subtypes of Breast Cancer
Authors: Kashyap Dharambir
Published: January 2025

Breast cancer heterogeneity has been well understood based solely on tumor components. However, the tumor microenvironment, which plays a crucial role in cancer by regulating tumor cells’ differentiation, maturation, and malignant potential, remains under-explored. This study conducted high-throughput RNA-Seq analysis on fresh breast cancer tissues from each molecular subtype and a pure population of cancer-associated fibroblasts (CAFs) isolated from cancer tissue and adjacent normal parts. Based on their functions, we identified three populations of CAFs: a) immune response-related, b) ECM remodeling, and c) calcium/protein binding. Validation of differentially expressed genes among these CAF populations revealed subtype-specific correlations. For instance, CAFs expressing immune response-related genes were significantly enriched in Luminal A/B and TNBC (log +1-fold; p =0.00047), compared to Her-2 positive (log -2.3-fold; p =0.0026). ECM remodeling genes exhibited greater expression in Her-2 positive and TNBC (log +4 to +11-fold; p =7.87E-08) when compared to Luminal subtypes (log +1.5-fold to +6-fold; p =8.66E-05). Calcium binding genes displayed overall similar expression across breast cancer subtypes. Thus, this study identified and underscored the functional heterogeneity of CAFs within the tumor microenvironment across the molecular subtypes of breast cancer.
Prospective screening for monkeypox infection among men who have sex with men at an infectious diseases’ outpatient clinic in Copenhagen, Denmark
Authors: Miranda Freire De Andrade Nuno Felipe , Pinholt Mette , Korsholm Mindedahl Nyamadi Julie Maria , Kronborg Gitte , Engsig Frederik Neess
Published: January 2025

Since 2022, over 102,000 cases of mpox clade IIb have been reported worldwide, primarily affecting men who have sex with men. Key risk factors include the use of HIV pre-exposure prophylaxis (PrEP) and HIV infection. In Denmark, the smallpox vaccine (Imvanex®) has been available to at-risk individuals since 2022. However, cases of reinfection with mpox have raised concerns about immunity, asymptomatic transmission.

Between August and October 2023, we screened 123 PrEP users for mpox at an outpatient clinic at Copenhagen University Hospital Hvidovre, Denmark. Mpox PCR testing was conducted using rectal swabs. Among the participants, 97% had received at least one dose of the mpox vaccine. No mpox cases were detected.

These findings suggest that, in a highly vaccinated high-risk population during a period of very low mpox prevalence in Denmark, asymptomatic mpox circulation is unlikely. The results support the current strategy of focusing mpox testing on symptomatic individuals and contact tracing during low-prevalence periods with high vaccination coverage.
Potential of ChatGPT in Youth Mental Health Emergency Triage: Comparative Analysis with Clinicians
Authors: Thotapalli Samanvith , Yilanli Musa , McKay Ian , Leever William , Youngstrom Eric , Harvey-Nuckles Karah , Lowder Kimberly , Schweitzer Steffanie , Sunderland Erin , Jackson Daniel I. , Sezgin Emre
Published: January 2025

Background

Large language models (LLMs), such as GPT-4, are increasingly integrated into healthcare to support clinicians in making informed decisions. Given ChatGPT’s potential, it is necessary to explore such applications as a support tool, particularly within mental health telephone triage services. This study evaluates whether GPT-4 models can accurately triage psychiatric emergency vignettes and compares its performance to clinicians.

Methods

A cross-sectional study with qualitative analysis was conducted. Two clinical psychologists developed 22 psychiatric emergency vignettes. Responses were generated by three versions of GPT-4 (GPT-4o, GPT-4o Mini, GPT-4 Legacy) using ChatGPT, and two independent nurse practitioners (clinicians). The responses focused on three triage criteria: risk (Low 1-3 High), admission (Yes-1; No-2), and urgency (Low 1-3 High).

Results

Substantial interrater reliability was observed between clinicians and GPT-4 responses across the three triage criteria (Cohen’s Kappa: Admission = 0.77; Risk = 0.78; Urgency = 0.76). Among the GPT-4 models, Kappa values indicated moderate to substantial agreement (Fleiss’ Kappa: Admission = 0.69, Risk = 0.63, Urgency = 0.72). The mean scores for triage criteria responses between GPT-4 models and clinicians exhibited consistent patterns with minimal variability. Admission responses had a mean score of 1.73 (SD = 0.45), risk scores had a mean of 2.12 (SD= 0.83), and urgency scores averaged 2.27 (SD = 0.44).

Conclusion

This study suggests that GPT-4 models could be leveraged as a support tool in mental health telephone triage, particularly for psychiatric emergencies. While findings are promising, further research is required to confirm clinical relevance.