bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantifying the Diagnostic Odyssey Burden Among Persons with Inborn Errors of Immunity
Authors: Nikzad Sarina , Johnson Rebekah , Scalchunes Chrisopher , Rider Nicholas L.
Published: December 2024

Purpose
Patients with inborn errors of immunity (IEI) have lifelong health complications including severe infections and physical impairments. Previous studies show that a patient’s perception of their health is an important predictor of health outcomes. The purpose of our study is to understand factors related to patient reported overall health status.
Methods
We used data from the Immunodeficiency Foundation (IDF) 2017 National Patient Survey and analyzed factors which correlated with the reported health status (RHS). Among a cohort of 1139 self-reported IEI patients, we identified age at the time of diagnosis, time gap between symptom onset and diagnosis, number of physicians seen, and whether the diagnosis was made in the first 5 years of life as significant. We used a two-tailed t-test, single-factor ANOVA, and Tukey-Kramer post-hoc test to analyze the statistical significance in the observed difference.
Results
Patients who received a diagnosis before the age of 12 had a significantly better RHS (n = 207 pre-12a vs. n = 900 post-12a; p < 0.0001). Patients who received a diagnosis within 10 years of symptom onset showed improved RHS (n = 413 pre-10s vs. n = 524 post-10s; p = < 0.0001). Among patients who had symptom onset within the first 5 years of life, those who received a diagnosis had a significantly improved RHS (n = 275 undiagnosed pre-5a vs. n = 108 diagnosed pre-5a; p < 0.0001). Finally, RHS was significantly impacted by the number of physicians they saw (n = 252 low vs. n = 886 high; p = < 0.0001).
Conclusion
These findings shed light upon critical factors which impact IEI patients’ RHS.
Routine cold storage leads to hyperacute graft loss in pig-to-primate kidney xenotransplantation; hypothermic machine perfusion may be preferred preservation modality in xenotransplantation
Authors: Yamada Kazuhiko , Hisadome Yu , Eisenson Daniel , Chen WeiLi , Schulick Alex , Santillan Michelle , Luo Adam , Casella Kelly , Gu Du , Sekijima Mitsuhiro , Sahara Hisashi , Warren Daniel , Cameron Andrew , Iwase Hayato , Shenderov Eugene
Published: December 2024

Xenotransplantation (XTx) is an increasingly realistic solution to the organ shortage. Clinical XTx may require off-site procurement in a designated pathogen free (DPF) facility necessitating a period of cold ischemic time during transportation. This study evaluates the impact of different kidney preservation strategies on early graft function in pig-to-baboon XTx in a series of eight cases of pig-to-baboon xenotransplantation performed after five hours of cold ischemic time and compares these results to six cases of pig-to-baboon xenotransplantation performed with minimal ischemic time. Our data indicates that porcine kidneys appear to be particularly sensitive to IRI after cold preservation, especially across xenogeneic barriers, and routine static cold storage leads to hyperacute graft loss even in recipients with low levels of preformed antibodies. Hypothermic machine perfusion minimizes IRI and may prevent early xenograft loss.
Lenalidomide in combination with Rituximab, Dexamethasone, High-dose ARA-C and Cisplatinum as Salvage Therapy in Refractory or Relapsed Aggressive B-cell Non-Hodgkin-Lymphoma - An open-label, multicentre phase I/II study (DSHNHL-R6)
Authors: Fuhrmann Stephan , Nickelsen Maike , Hasenkamp Justin , Hüttmann Andreas , Dreyling Martin , Kiehl Michael , Salwender Hans , Placzek Marius , Schmitz Norbert , Glass Bertram
Published: December 2024

Treatment of relapsed and refractory large cell B-NHL (LBCL) is still an unmet medical need. Platinum-containing salvage immunotherapies achieve remission rates of 40-60 %. The phase I/II DSHNHL-R6 trial sought to investigate feasibility, safety and efficacy of R-DHAP plus lenalidomide in patients with first or subsequent relapse of LBCL.
35 patients were enrolled in the trial and 33 could be analyzed (ITT). Lenalidomide dose was stepwise increased if no dose-limiting toxicities were observed.
MTD for lenalidomide in combination with R-DHAP was 15 mg administered on days 1-7 of each cycle. The overall response rates (ORR; defined as complete, unconfirmed complete or partial remission) and complete response rates (CR) rates were 62.5% and 29.0% for the ITT-population and 81.3% and 50.0% in the patients treated as per protocol (PP). With a median follow-up of 13.9 months, the median OS was 21.2 months and PFS for the ITT and PP-population were 10.7 and 18.9 months respectively. No treatment related deaths were observed. Haematologic adverse events (77% grade 3-4) were common.
Combining Lenalidomide with R-DHAP is an effective and tolerable salvage therapy for patients with LBCL.(registered at www.clinicaltrialsregister.eu; EudraCT number: 2009-010824-25; Start Date: 2010-04-12)
Deep learning algorithms enable MRI-based scapular morphology analysis with values comparable to CT-based assessments
Authors: Hess Hanspeter , Oswald Alexandra , Rojas J Tomás , Lädermann Alexandre , Zumstein Matthias A. , Gerber Kate
Published: December 2024

Scapular morphological attributes show promise as prognostic indicators of retear following rotator cuff repair. Current evaluation techniques using single-slice magnetic-resonance imaging (MRI) are, however, prone to error, while more accurate computed tomography (CT)-based three-dimensional techniques, are limited by cost and radiation exposure. In this study we propose deep learning-based methods that enable automatic scapular morphological analysis from diagnostic MRI despite the anisotropic resolution and reduced field of view, compared to CT. A deep learning-based segmentation network was trained with paired CT derived scapula segmentations. An algorithm to fuse multi-plane segmentations was developed to generated high-resolution 3D models of the scapula on which morphological landmark- and axes were predicted using a second deep learning network for morphological analysis. Using the proposed methods, the critical shoulder angle, glenoid inclination and version were measured from MRI with accuracies of -1.3 ± 1.7 degrees, 1.3 ± 2.1 degree, and − 1.4 ± 3.4 degrees respectively, compared to CT. Inter-class correlation between MRI and CT derived metrics were substantial for the glenoid version and almost perfect for the other metrics. This study demonstrates how deep learning can overcome reduced resolution, bone border contrast and field of view, to enable 3D scapular morphology analysis on MRI.
Single-Cell RNA Sequencing to Identify an Immunogenic Cell Death-Related Prognostic Signature in Intrahepatic Cholangiocarcinoma
Authors: Sha Bowen , Tong Fei , Shu Qinghua , Wu Miao , Zhao Liang , Zhang Yufeng
Published: December 2024

Immunogenic cell death (ICD) is crucial for cancer development and enhances the effectiveness of immunotherapy by triggering an adaptive immune response. However, the impact of ICD-related genes (ICDRGs) on iCCA progression and patient prognosis remains unclear. iCCA samples from The Cancer Genome Atlas (TCGA) were categorized into two ICD-associated subtypes by consensus clustering, and patient prognosis in these subgroups was assessed. Single-cell RNA sequencing was conducted on viable cells from 8 iCCA patients to understand their transcriptomic profiles, heterogeneity, and immune microenvironment. Principal component analysis (PCA) and uniform manifold approximation and projection (UMAP) analysis were applied to identified 13 cell subpopulations. The gene set enrichment analysis (GSEA) was used to investigate pathway heterogeneity among these subpopulations. CellChat was employed for intercellular communication analysis. Pseudotime trajectory analyses with CytoTRACE and Monocle2 were used to explore differentiation trajectories and functional differences across various states. 30485 single cells from human iCCA and normal tissues were sequenced, revealing two ICD-associated subtypes. The ICD-low subtype correlates with better clinical outcomes, whereas the ICD-high subtype is linked to increased immune cell infiltration and immune response signaling activity. Distinct biological functions and metabolic characteristics were observed in iCCA between high- and low-ICD groups. High infiltration of ICD-low subtype in iCCA is associated with poor prognosis, potentially through the ANXA-FPR pathway affecting macrophage proliferation and differentiation. Our study constructed an immunogenic cell death-related signature that can promise prognosis prediction and personalized medicine in iCCA. This finding might help guide clinicians for iCCA patients.
Untargeted Metabolomics Reveals Key Pathways in Miscarriage: Steroid, Folate, Fatty Acid & Glycosaminoglycan Metabolism
Authors: Ku Chee Wai , Tan Yu Bin , Chew Kuan Yang , Ku Chee Onn , Ng Carissa , Sultana Rehena , Tan Thiam Chye , Lee Yie Hou
Published: December 2024

Metabolites influencing miscarriage outcomes remain understudied. We hypothesized that aberrant metabolism impacts threatened miscarriage outcomes and that understanding these pathways could offer new management strategies. This case-control study analyzed serum metabolomics from 80 women between 5-12 weeks’ gestation at KK Women’s and Children’s Hospital, Singapore, comparing three groups: women with threatened miscarriage who miscarried (TMMC), those with ongoing pregnancies (TMO), and women with normal pregnancies (NP). Using untargeted liquid chromatography-mass spectrometry and pathway analysis through MetaboAnalyst 5.0 and the Kyoto Encyclopedia of Genes and Genomes, 267 metabolites across 12 enriched pathways were identified. Dysregulations in steroid (AUC 0.82), folate (AUC 0.59), fatty acid (AUC 0.70), and glucosaminoglycan (AUC 0.64) pathways distinguished women who miscarried from those with ongoing pregnancies. We provide initial insights into the metabolic profile associated with miscarriage, highlighting disruptions in steroid hormone, fatty acid, folate, and glucosaminoglycan biosynthesis. Further validation may support biomarker development for prognostication.
Factors affecting intensive care length of stay in critically ill pediatric patients with burn injuries
Authors: Lerner Reut Kassif , Gibori Amit , Hubara Evyatar , Sadeh Tal , Rubinstein Marina , Paret Gidi , Pessach Itai M.
Published: December 2024

Background
Burns in children are often complex injuries, leading to prolonged length of stay (LOS) and significant morbidity. LOS in pediatric intensive care units (PICUs) is a key measure for evaluating illness severity, clinical outcomes, and quality of care. Accurate prediction of LOS is vital for improving care planning and resource allocation. There is limited data for predicting LOS in severely burned children in PICU. This study aims to identify significant factors associated with prolonged PICU stays and offer a simple LOS predicting model.
Methods
This historical cohort study included all patients < 18 years, admitted for severe burn injuries to Israel’s largest tertiary hospital PICU, from 2015 to 2020. Statistical analyses were conducted to identify factors linked to prolonged LOS, and a predictive model was designed.
Results
The study included 39 pediatric burn patients and identified several factors associated with longer PICU stays. Patients with "long LOS" had significantly higher %TBSA (33.11 ± 17.87% vs. 16.67 ± 7.98%, p < 0.001. During the first 24 and 48 hours, the "long LOS" group had lower minimal systolic blood pressure (SBP) (70.67 ± 17.49 mmHg vs. 84.38 ± 16.73 mmHg, p = 0.015 and 69.39 mmHg ± 16.44 vs. 81.10 mmHg ± 19.67, p = 0.018). Although serum lactate levels were higher in the "long LOS" group, the difference was not significant, and platelet counts in this group were significantly lower during the first 48 hours (184 K/µL vs. 264.5 K/µL, p = 0.003). A predictive model based on %TBSA, SBP, lactate, and platelet count was developed, demonstrating 100% specificity and positive predictive value for predicting LOS over 7 days in severely burned children.
Conclusions
Key clinical indicators at PICU admission in severely burned children were associated with LOS > 7 days. The resulting predictive model, although requiring further validation in multi-site studies, offers a promising tool for enhancing care planning in this population.
Utility of Prostate-Specific Antigen Derivatives to Minimize Unnecessary Magnetic Resonance Imaging in Patients with Prior Negative Prostate Biopsy Running title: PSAD to Minimize MRI in Prior Negative Prostate Biopsy
Authors: Lee Sangchul , Ryu Hoyoung , Song Sang Hun , Hwang Sung Il , Lee Hak Jong , Lee Hakmin , Hong Sung Kyu , Byun Seok-Soo , Song Byeongdo
Published: December 2024

Magnetic resonance imaging (MRI) has become an important tool for recommending prostate biopsy (PB) in prostate cancer (PCa) detection. However, the routine use of MRI in patients with previous negative PB remains debatable. This study aimed to evaluate the utility of prostate-specific antigen (PSA) derivatives to guide MRI use and reduce unnecessary scans in such cases. Receiver operating characteristic analysis identified a Prostate Imaging Reporting and Data System score ≥ 4 as the optimal threshold for predicting clinically significant PCa (Gleason score ≥ 7). A cohort of 251 patients with at least one prior negative PB who underwent serum PSA testing, free PSA, and MRI between October 2015 and June 2024 were analyzed. The optimal cutoff values for PSA, PSA density (PSAD), and free-to-total PSA ratio (%fPSA) were 11.87 ng/mL, 0.19 ng/mL2, and 18.76%, respectively (all p < 0.001). Restricting MRI to patients with PSA < 11.87 ng/mL, PSAD < 0.19 ng/mL2, or %fPSA > 18.76% could induce MRI use by 22.7% while missing only 9.1% of significant PCa cases on MRI-targeted PB.
Acupuncture for Collaborative Efficiency in Eosinophilic Chronic Rhinosinusitis with Nasal Polyps After Nasal Surgery: A Randomized Controlled Trial Protocol
Authors: Huang Yue , Lv Zeyi , Pan Zhuo , Sui Wen , Chen Yulan , Li Qihong , Li Yu , Yin Man , Chen Xi , Yang Hao , Li Xinrong
Published: December 2024

Background: Eosinophilic chronic rhinosinusitis with nasal polyps(eCRSwNP) is a chronic inflammatory disease of the nasal and sinus mucosa dominated by eosinophil infiltration with polyp formation. both hormonal and surgical treatment face a high recurrence rate, with studies showing that when eosinophils constitute more than 27%, the recurrence rate of eCRSwNP is more than 90%. Hence, alternative therapy is needed. However, the insufficient randomized controlled trial limited the quality of evidence.
Methods: From November 2024 to April 2026, 84 acupuncture eCRSwNP patients after nasal surgery will be recruited at the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine. Participants will be randomized 1:1 to the acupuncture and sham acupuncture groups. The visual analogue scale (VAS), nasal sinus outcome test 22 (SNOT-22), and Lund-Kennedy endoscopic mucosal morphology score are used as the main outcome measures, and the SAS anxiety self-rating scale is used as the secondary outcome measures. Assessments are performed before and at the end of each week and at the end of 1 month, a total of 6 times.
Expected Results and Conclusion: We will be able to measure the effectiveness of acupuncture in patients with eCRSwNP and whether acupuncture is superior to sham acupuncture and usual care. The proposed acupuncture treatment might provide an alternative option for those patients.
The study was registered with the Chinese Clinical Trial Registry on 1 November 2024. (identifier: ChiCTR2400091693)
Antitumor activity of Gilteritinib, an inhibitor of AXL, in human solid tumor
Authors: wang liefeng , Zhang Zuxiong , Hu Ruxia , Liu Jie , Yang Xiaohan , Xiao Youban , Xu Xi , Liu Xinxin , Zeng Wen , Zhang Shuyong
Published: December 2024

AXL, a receptor tyrosine kinase, has recently emerged as a potential therapeutic target against various cancer types. Gilteritinib, a FDA-approved small-molecule inhibitor, is used for the treatment of patients with FLT3-mutated acute myeloid leukemia. However, the antitumor activity of Gilteritinib in solid tumors remains poorly elucidated. Here, The antitumor activity of Gilteritinib and molecular mechanisms underlying were explored in the AXL- expressing esophageal cancer (EC), ovarian cancer (OC) and gastric cancer (GC). Our data demonstrated that Gilteritinib significantly inhibited cell proliferation and spheroids formation via triggering apoptosis and cell cycle arrest in AXL-positive EC, OC and GC cells. Moreover, we found that Gilteritinib treatment repressed EC, OC and GC cell migration and invasion. Mechanistically, RNA-seq analysis revealed that Gilteritinib significantly downregulated multiple cancer-related pathways, such as apoptosis, cell cycle, mTOR pathway, AMPK pathway, p53 pathway, FOXO pathway, Hippo pathway and Wnt pathway, etc. Furthermore, Gilteritinib inhibited a unique set of E2F and MYC targets-associated genes in EC, OC and GC cells. Intriguingly, interrogation of the EC, OC and GC cohort demonstrated that these genes were overexpressed and associated with poor prognosis. Finally, Gilteritinib also displayed strong antitumor effects on AXL-positive PDX-derived explants (PDXEs) and PDX-derived organoids (PDXOs) ex vivo, and PDXs in vivo. Collectively, these findings reveals Gilteritinib as a potent therapeutic agent for the treatment of AXL-positive solid tumors.
Vessel volume decrease during early brain injury period as predictor for evolving delayed cerebral ischemia after SAH – a case-control study
Authors: Pantel Tobias , Kranawetter Beate , Sauvigny Jennifer , Ricklefs Franz L. , Drexler Richard , Thaler Christian , Malinova Vesna , Meyer Hanno S. , Czorlich Patrick , Sauvigny Thomas , Mielke Dorothee , Dührsen Lasse
Published: December 2024

Introduction: Delayed cerebral ischemia (DCI) secondary to aneurysmal subarachnoid hemorrhage (SAH) is a feared complication with frequent negative impact on the neurological outcome. Although early diagnosis and treatment is crucial, identifying patients at increased risk is difficult despite clinical risk stratifies such as the VASOGRADE score. Since a reduction in vessel volumes occurs regularly in this cohort and may indicate evolving DCI, the aim of this study was to investigated the reduction in vessel volume in the early brain injury (EBI) phase as an additional predictive marker for the development of DCI.
Methods: A bi-centric retrospective case-control study for the period 01/2018 to 12/2020 was conducted. Inclusion criteria were 1) angiographically confirmed aneurysmatic bleeding source and 2) cranial CT (CCT) scan with CT-angiography on admission (SAH onset) and between EBI (day 1–3). Patient-related, disease-specific and outcome parameters (modified Rankin scale (mRs)) were collected. VASOGRADE score was calculated and the volume of M1 segments of the middle cerebral arteries were measured. Subsequently, the occurrence of DCI was unblinded and the data were statistically analyzed.
Results: 80 patients met the inclusion criteria, of those 32 developed a DCI. Vessel volume was reduced in the DCI cohort at SAH onset (0.072 ± 0.027 cm3 vs. 0.108 ± 0.029 cm3, p < 0.001) and during EBI period (0.085 ± 0.028 cm3 vs. 0.121 ± 0.029 cm3, p < 0.001). ROC-analysis unveiled a volume of 0.095 cm3 AUC 0.836; p < 0.001) at SAH onset and 0.105 cm3 (AUC 0.837; p < 0.001) for the EBI period as predictive for the development of DCI. The predictive statistical markers of the volume threshold were superior to those of the VASOGRADE score.
Conclusions: Our data indicate that a reduction in vessel volume during the early brain injury (EBI) phase is a predictive marker for delayed cerebral ischemia (DCI). Furthermore, the statistical parameters associated with the volume threshold suggest that it serves as a more accurate predictor of DCI risk compared to the VASOGRADE score.
Long non-coding RNA PRKG1-AS1 Promotes Cell Proliferation and Migration in Lung Adenocarcinoma
Authors: Jiao Tong , Wen Haimei , Zeng Lizhong , Chen Yang , Shi Jie , Yang Shuanying
Published: December 2024

In previous studies, we have discovered a significant correlation between cGMP-dependent protein kinase I antisense RNA 1 (PRKG1-AS1) and the prognosis of lung adenocarcinoma (LUAD). Through analysis of The Cancer Genome Atlas (TCGA) database and expression data from non-small cell lung cancer tissues and cells, we found that PRKG1-AS1 is overexpressed in LUAD tissues. High expression of PRKG1-AS1 is associated with poor prognosis in LUAD patients. Cox regression analysis revealed that PRKG1-AS1 is an independent factor affecting the prognosis of LUAD. Gene Set Enrichment Analysis (GSEA) results indicated that PRKG1-AS1 might participate in various cancer-related biological processes and signaling pathways, including immune response. Furthermore, our study demonstrated that knockdown of PRKG1-AS1 expression inhibited proliferation and metastasis in LUAD. Correlation analysis between PRKG1-AS1 and protein-coding genes (PCGs) revealed a positive correlation between PRKG1-AS1 and dickkopf-1 (DKK1). Downregulation of PRKG1-AS1 led to decreased expression of DKK1, which is highly expressed in LUAD and is associated with poor prognosis. In summary, our findings suggest that PRKG1-AS1 may function as an oncogene contributing to the development of LUAD and holds significant prognostic value.
PPP5C pathogenic variant identified: a potential key to gaining insight into developmental and epileptic encephalopathy?
Authors: Falsaperla Raffaele , Sapuppo Annamaria , Pappalardo Xena Giada , Rizzo Roberta , Rocca Roberta , Fusto Gaia , Marino Silvia , Sortino Vincenzo , Saccuzzo Lucia , Ruggieri Martino , Fichera Marco
Published: December 2024

Background Emerging evidence suggesting a possible link between the PPP5C gene (Protein Phosphatase 5 Catalytic Subunit; OMIM#600658) and developmental and epileptic encephalopathy (DEE, OMIM#308350), although the clinical significance of pathogenic variants in this gene remains unclear. PPP5C is a member of the protein phosphatase catalytic subunit family, which is involved in various signaling pathways governing cell growth, differentiation, and responses to hormonal signals or cellular stress. To date, only one case with a PPP5C variant has been reported, associated with a severe neurological phenotype, including microcephaly, failure to thrive, and early-onset seizures.Results We report a 12-year-old girl affected by epilepsy and learning disorders. At the age of five, she presented convulsive status epilepticus with respiratory failure at onset and she started anticonvulsant therapy with Levetiracetam with a significant improvement. Genetic analysis revealed a de novo heterozygous missense variant of PPP5C gene (c.202C > T: p.Arg68Cys), which had not been previously described in the literature.Conclusion This case expands the phenotypic spectrum associated with PPP5C variants, highlighting the potential role of this gene in neurological disorders. Our findings may provide some valuable insights into the spectrum of phenotypic manifestations linked to this gene less investigated in neuropediatrics.
Development of a prediction system for KRAS mutation detection via circulating tumour DNA analysis among patients with unresectable pancreatic cancer
Authors: Shimizu Hiroshi , Suzuki Rei , Asama Hiroyuki , Sugimoto Mitsuru , Sato Kentaro , Ohira Rei , Kametaka Akira , Nakamura Jun , Kato Tsunetaka , Yanagita Takumi , Hikichi Takuto , Takagi Tadayuki , Ohira Hiromasa
Published: December 2024

Background
Pancreatic cancer (PC) is an aggressive malignancy with a poor prognosis and limited treatment options. Advances in molecular profiling and liquid biopsy, specifically the detection of circulating tumour DNA (ctDNA), offer new avenues for personalized therapy. KRAS mutations are present in approximately 63–70% of PC patients, but detection via liquid biopsy can be influenced by disease stage, metastasis site, and ctDNA concentration. The aim of this retrospective study was to develop a prediction model for KRAS mutation detection in unresectable PC patients using clinical variables.
Methods
We analysed 32 patients who underwent ctDNA testing from 2019 to 2024, utilizing FoundationOne® Liquid CDx and Guardant360® CDx panels. Multivariate analysis of the clinical factors was performed via logistic regression with stepwise selection to elucidate independent predictors of KRAS mutation detection. According to the independent predictors of successful KRAS detection, a nomogram was plotted
Results
Multivariate analysis revealed that liver metastasis, multiple metastatic sites, and disease progression were significant predictors of successful KRAS mutation detection. A nomogram and ROC curve demonstrated high predictive accuracy, with a sensitivity of 70%, specificity of 90.9%, and AUC of 0.83.
Conclusions
Our prediction system effectively stratified patients by the likelihood of KRAS mutation detection, offering a practical tool for selecting candidates for liquid biopsy. These findings underscore the importance of personalized approaches in PC management and suggest that patients without these key clinical factors may not benefit from ctDNA testing. Future studies should validate this model in larger cohorts.
Association between remnant cholesterol levels and reversion to normoglycemia from prediabetes: a 5-year longitudinal cohort study of Chinese non-obese adults
Authors: Liu Wei , Jian Wenjing , Lin Suina , Huang Zhenhua
Published: December 2024

The primary objective of this study is to explore the relationship between remnant cholesterol (RC) levels and the reversion to normoglycemia in non-obese Chinese individuals with prediabetes. To achieve this goal, we conducted a retrospective cohort study involving 8,109 non-obese prediabetic participants in China, using the Cox proportional hazards regression model to analyze the correlation between RC and the likelihood of returning to normoglycemia. The results indicate a significant negative correlation between RC levels and reversion to normoglycemia (HR = 0.55, 95% CI: 0.47–0.64). Specifically, as RC quartiles increase, the probability of reverting to normoglycemia significantly decreases, with participants in the highest quartile having a 49% lower likelihood of recovery compared to those in the lowest quartile. Furthermore, we identified a nonlinear relationship between RC and the reversion to normoglycemia, with 1.47 mmol/L established as the inflection point. When RC levels are below this threshold, decreasing RC significantly increases the likelihood of recovery, whereas above this threshold, the relationship is no longer significant. To further validate the robustness of our findings, we conducted sensitivity and subgroup analyses, all of which support the reliability of the main results. In summary, there exists a significant negative and nonlinear relationship between RC levels and the reversion to normoglycemia in non-obese Chinese prediabetic patients. This suggests that lowering RC levels may play an important role in the blood glucose recovery of these patients. Aggressive interventions aimed at reducing RC levels below 1.47 mmol/L may significantly enhance the chances of prediabetic patients returning to normoglycemia.
Characteristics and prevalence of MHT use among women aged 40-65 years with low socioeconomic status: a multi-district study in Shanghai, China
Authors: Zhou Yang , Li Changbin , Sun Yixuan , Zhang Dongyao , Wang Zhijie , Wang Mei , liu Zhou , Fengyun Yang , Su Minjun , Pang Xixia , Jin Ruifu , Xu Fengyin , Chen Xuelian , Zhang Lin , Teng Yincheng , Tao Minfang
Published: December 2024

Background:
China faces a burgeoning demand for menopausal health care. Guidelines recommend Menopausal Hormone Therapy (MHT) as the most effective treatment for menopausal symptoms. However, the prevalence of MHT use and its influencing factors remains largely unknown in China, especially for women with minimal assurance.
Objective: This multi-center study aimed to explore the prevalence of MHT use with low socioeconomic status in shanghai and to understand its factors associated with MHT use.
Methods and design
We conducted a cross-sectional, multi-district, large-scale study of 6068 women aged 40-65 years with minimal living assurance from 10 health facilities in 7 districts of Shanghai supported by the Chinese government's public health benefit program. Data from cross-sectional survey of women between January 2023 and September 2023 were collected from comprehensive and modified questionnaires. Odds ratios (ORs) were calculated using logistic regression for characteristics related to MHT use, adjusting for sociodemographic, reproductive, health and lifestyle factors.
Discussion
This was the first largest of all similar studies to investigate the prevalence and the specific determinants of MHT use in southeast China. Our study revealed a low rate of MHT prescription among women with minimal assurance in Shanghai and MHT use was independently associated with undergoing a dual energy x-ray absorptiometry (DXA) scan, family history of osteoporosis, hospital-based sample source, regular physical activity, menopause, employment and higher educational level. It raises the need for increased awareness and strategies to help women seek menopausal health care of socioeconomic deprivation.
Trial registration: chiCTR-EPC-17011255.
Trends in prevalence, associated comorbid burden, and subsequent mortality of social isolation: A gender perspective
Authors: Shu Xukai , Sun Zihui , Yang Yipeng , Huang Huiming , Guo Qian , Ye Linjie , Qiu Weida , Zhang Zhan , Wu Shike
Published: December 2024

Background
Social isolation has been a major public health issue associated with increased mortality. However, gender differences in social isolation have not been thoroughly characterized. This study aimed to estimate the gender differences in the trends in the prevalence of social isolation, evaluate the gender-based differences in its comorbid burden, and examine their subsequent associated mortality by gender.
Methods
This nationwide cross-sectional and prospective cohort study used data from the China Health and Retirement Longitudinal Study. Social isolation was measured using 4 dichotomized indicators. The Cochran-Armitage trend test and multivariate Poisson regression models were constructed to analyze the trends in social isolation and the longitudinal associations between social isolation and mortality by gender. All analyses were weighted to account for the multistage, probability-proportional-to-size sampling scheme.
Results
Among the 10197 participants, the mean age was 60.0 years, and 48.1% were men. The prevalence of social isolation was 20.8%, with an average age-adjusted Charlson Comorbidity Index (ACCI) of 2.7 (± 1.8) and 1.5 (± 1.4) comorbidities. A significant downward trend in social isolation was observed in men, with a weighted prevalence of 19.4% (95% confidence interval (CI): 17.7, 21.3) in 2011 and 14.1% (95% CI: 12.9, 15.4) in 2018 (P for trend < 0.001). In contrast, a stable trend in social isolation was noted in women, with a weighted prevalence of 24.0% (95% CI: 22.5, 25.6) in 2011 and 24.1% (95% CI: 22.7, 25.6) in 2018 (P for trend = 0.154). A steeper increase in ACCI and number of comorbidities was observed in women compared to men. (P for gender-by-social isolation score interaction < 0.001) Over a 9-year follow-up period, females with social isolation had more than double the risk of mortality (incidence rate ratio (IRR): 2.05, 95% CI: 1.65, 2.53), while males with social isolation had only a 60% increased IRR (95% CI: 1.31, 1.95) of all-cause mortality (P for interaction = 0.032).
Conclusion
Several gender differences in social isolation were observed, including the higher prevalence, heavier comorbid burdens, and a more prominent impact on mortality noted in women, highlighting the importance of enhancing family and social support for older adults, particularly in improving the socioeconomic statuses and rights of women.
Oral Health, DMFT and Disease Prevalence Among HIV-Positive Patients in Tabriz, Iran in 2024
Authors: Ghahremani Saman Khodavirdizadeh , Shayan Ramin Ghasemi , Kia Seyed Javad , Ghahremani Gholamreza Khodavirdizadeh , Sani Sahba Khosousi
Published: December 2024

Background In HIV-positive patients, due to weak immunity, long-term use of drug treatment, stigma and discrimination, oral and dental problems are more common than in the non-affected population. Lack of adequate attention and planning to facilitate their access to oral and dental care and treatment services without stigma and discrimination and at low cost causes the reduction of referrals or concealment of the disease and as a result the exacerbation of the underlying oral and dental disease and the possibility of the disease spreading to the patient's relatives and health personnel.Materials and methods Demographic information of the patients was extracted from the counseling center software. After obtaining consent, the examination and filling of the questionnaire was done. The results were entered and analyzed in SPSS 26 software.Results Out of 134 patients studied, 96 were men and 38 were women. The average age of all patients was 44 years and the average duration of the disease was 106 months. Less than five percent of the patients were in the AIDS stage. The average DMFT of all patients was 16.7 and it had a significant correlation with smoking, drug use, education level and CD4 count. The prevalence of periodontal disease was 69%, angular cheilitis was 17.9% and aphthous ulcer was 16.4%. Mucosal lesions (candida, hairy leukoplakia and cancer) had a prevalence of less than five percent. The most important reasons for not receiving dental services were financial poverty (66%), stigma and discrimination (27%).Conclusion The prevalence of oral and dental diseases in patients with HIV is very high and it is necessary to include free or low-cost dental services without stigma and discrimination in the description of the duties of counseling, care and treatment centers for behavioral diseases.
Efficacy of Revisional Endoscopic Sleeve Gastroplasty After Laparoscopic Sleeve Gastrectomy
Authors: Deng John , Wool Julia , Montecino Ronald Blanco , Arbaiza Alvaro Cadillo , Xie Luyu , Messiah Sarah E. , Matthew Sunil , Shiffer Shannon , Almandoz Jaime P. , Tavakkoli Anna
Published: December 2024

Introduction
Recurrent weight gain after laparoscopic sleeve gastrectomy (LSG) is common. Revisional endoscopic sleeve gastroplasty (r-ESG) has been shown to be a promising endoscopic bariatric therapy (EBT) to treat weight recurrence after LSG. However, to date, weight loss outcomes beyond one-year follow-up are unknown. Our study aims to: 1) Examine one year, 18-month, and 24-month weight loss outcomes post-r-ESG; 2) Determine if weight loss outcomes post-LSG predict clinical outcomes post-r-ESG.
Methods
This was a retrospective cohort data of patients who completed r-ESG from December 2020 to November 2023. The primary outcome was percentage of total body weight loss (TBWL) at one-year post-r-ESG. Secondary outcomes included TBWL at 18- and 24- month post-r-ESG. Multivariable logistic regression analysis was used to determine predictors of weight loss ≥ 5% at 12 months.
Results
A total of 55 patients completed r-ESG. TBWL post-r-ESG at 12-months was 8.6% (n = 37), at 18-months was 10.7% (n = 31), and at 24 months was 12.6% (n = 18) [Table 2] There were no statistically significant variables associated with weight loss ≥ 5% at 12 months [Table 3].
Conclusion
Our study demonstrates that r-ESG is an effective and durable EBT for post-LSG weight recurrence. Further research is needed to determine optimal timing of r-ESG for weight recurrence as well as the adjunctive role of anti-obesity medications.
RMX1002 as monotherapy and in combination with anti-PD-1 antibody in advanced solid tumors: a phase I dose-escalation and expansion study
Authors: Liu Dan , Gong Jifang , Zhang Jian , Shu Yongqian , Wu Hao , Liu Tianshu , Xu Yanhua , Zhang Lijia , Li Min , Hu Xichun , Shen Lin
Published: December 2024

Background: RMX1002 (grapiprant) is a selective E-type prostanoid receptor 4 (EP4) antagonist and a promising candidate for cancer therapy, potentially enhancing anti-tumor immune responses. This study aimed to evaluate the safety, pharmacokinetics, pharmacodynamics, and efficacy of RMX1002 as monotherapy and in combination with anti-PD-1 antibody toripalimab for advanced solid tumors. Patients and Methods: This multicenter, phase I trial enrolled patients with histologically or cytologically confirmed advanced solid tumors. This study included three phases: Ia (dose-escalation of RMX1002 monotherapy from 200 to 650mg BID), Ib (dose-escalation from 500 to 650mg BID in combination with toripalimab), and Ic (dose-expansion of 500mg BID with toripalimab). Safety, pharmacokinetics, pharmacodynamics, and efficacy were assessed.
Results: A total of 45 patients were enrolled (17 in phase Ia, 12 in phase Ib, and 16 in phase Ic). No dose-limiting toxicity was reported, and the MTD was not reached. Overall, 21 patients experienced RMX1002-related adverse events with CTCAE grade ≥3. Pharmacokinetics revealed rapid absorption of RMX1002 with the maximum concentration (Cmax) reached within 2 to 5 hours, and dose-dependent increases in Cmax and area under the concentration-time curve. The increase in urinary metabolite of PGE2 suggested the inhibition of EP4 signaling pathway. The best response of stable disease was reported in 64.7%, 28.6%, and 18.8% of patients in phase Ia, Ib, and Ic, respectively.
Conclusion: RMX1002 was well tolerated at the tested doses and showed signs of antitumor activity. RMX1002 500 mg BID with toripalimab 240 mg biweekly was selected as the recommended dose for future clinical trials.
Structural identification of the RY12 domain of RyR1 as an ADP sensor and the target of the malignant hyperthermia therapeutic dantrolene
Authors: Clarke Oliver , Kim Kookjoo , Li Huan , Yuan Qi , Melville Zephan , Zalk Ran , des Georges Amedee , Frank Joachim , Hendrickson Wayne , Marks Andrew
Published: December 2024

Malignant hyperthermia (MH) is a life-threatening pharmacogenetic condition triggered by volatile anesthetics, which activate pathogenic RyR1 mutants. The small molecule therapeutic dantrolene has long been used to treat MH. However, the binding site and mechanism of dantrolene remain unclear. Here, we present cryo-EM structures of RyR1 bound to dantrolene and the MH trigger agent 4-chloro-m-cresol (4CmC), revealing the dantrolene and 4CmC binding sites in atomic detail. Dantrolene binds stacked with ATP or ADP in the RY12 domain at the corner of the receptor, inducing a conformational change in this domain which is allosterically coupled to pore closure. Functional analyses revealed that ATP or ADP was required for dantrolene inhibition, and a single point mutation that disrupts the peripheral ATP binding site abolished ATP/ADP-dependent dantrolene inhibition. Strikingly, in the absence of dantrolene, this site selectively binds two ADP molecules, suggesting a possible role in ATP/ADP ratio sensing.
Structures and maps can be found here: https://www.dropbox.com/scl/fi/elb0vm1evd0y47lnt6mwz/RyR1_maps_and_models.zip?rlkey=0zguve9jievklj1fb9s3mburg&dl=0
SLC38A1 as a novel therapeutic target in upper tract urothelial carcinoma via regulating cell proliferation and migration through suppressing Akt/mTOR signaling
Authors: Cheng Yuan-Tso , Liu Yu-Liang , Tsai Wan-Chi , Chen Chien-Hsu , Kao Ying-Hsien , Chung Yueh-Hua
Published: December 2024

Upper tract urothelial carcinoma (UTUC) has specific high prevalence in Asian population and, compared to bladder cancer, there are unique etiologic and genomic factors contributing to its tumorigenesis. Although up-regulation of sodium-coupled neutral amino acid transporter 1 (SLC38A1) gene has been previously implicated as a promising therapeutic target for many tumors, the role of SLC38A1 in UTUC tumorigenesis, however, remains unknown. This study measured the expression levels of SLC38A1 protein in human renal pelvis carcinoma tissues and evaluated the effect of SLC38A1 gene silencing on behaviors of two UTUC cell lines, BFTC-909 and UM-UC-14. Immunohistochemical observation indicated that SLC38A1 was significantly up-regulated in UTUC lesion tissues compared to adjacent normal tissues. Using siRNA-mediated gene silencing approach, knockdown of SLC38A1 protein clearly showed inhibitory effects on proliferation and migration of UTUC cells. In addition, the SLC38A1 siRNA delivery significantly The SLC38A1 siRNA delivery effectively ameliorated the constitutive phosphorylation levels of Akt and mTOR, and simultaneously suppressed the expression of NF-κB and MMP-9 in the UTUC cells. In conclusion, our findings demonstrated that SLC38A1 may serve as a diagnostic and prognostic biomarkers in UTUC, and strongly suggested that SLC38A1 silencing is a novel therapeutic strategy for UTUC treatment.
Patient and provider perceptions of the impact of COVID-19 on tuberculosis healthcare access and delivery: A qualitative study of the complexities of a pandemic within a pandemic
Authors: Brehon Katelyn , Hung Pam , Miciak Maxi , Lau Angela , Heffernan Courtney , Ferrara Giovanni , Lim Rachel , Perreault Kadija , Weatherald Jason , Ronksley Paul E. , Stickland Michael K. , Gross Douglas P. , Lam Grace Y.
Published: December 2024

Objective: We aimed to explore patient and provider perspectives of the impact of the COVID-19 pandemic on tuberculosis healthcare access and service delivery.
Methods: We used Interpretive Description, a qualitative approach with the end-goal of informing decisions and actions in clinical practice. Levesque et al.’s “Conceptual framework of access to health care” informed the development of our interview guides. Interviews were conducted virtually and confidentially transcribed verbatim. Data generation and analysis occurred concurrently. Analysis was informed by Braun and Clarke’s six phases of reflexive thematic analysis. Strategies to enhance rigour and trustworthiness of the findings were utilized.
Results: We completed 15 interviews: 6 with patients and 9 with providers. Three key themes were generated: (a) Diagnostic hurdles created delay; (b) Hybrid services promote health equity; and (c) Navigating the complexities of a pandemic within a pandemic. Diagnosing tuberculosis was challenging even prior to the pandemic since some providers lacked experience and familiarity with the condition. The diagnostic process was further complicated with the onset of the COVID-19 pandemic. However, COVID-19 also introduced streamlined virtual care for patients which was convenient and improved access but was not viewed as being equivalent to in-person care. The intersection of the COVID-19 and tuberculosis pandemics created competition for limited resources while highlighting learnings that may positively impact future tuberculosis care.
Conclusions: Our findings can inform health system leadership about how the COVID-19 pandemic impacted care of other public health threats like tuberculosis, helping to prepare more effectively and equitably for future challenges.
Staple-Related Midgut Volvulus Following Appendectomy: A Pediatric Case Report and a Comprehensive Literature Review
Authors: Montero Javier Arredondo , Villafañe Alicia Escudero , Ruiz María Rodríguez
Published: December 2024

The development of an intestinal volvulus after an appendectomy is an exceptional and extremely serious complication. A 12-year-old female patient underwent surgery for uncomplicated acute appendicitis. The surgery and postoperative period were uneventful. Two and a half months later, she presented with an acute abdomen. Radiological studies confirmed a midgut volvulus and identified a free surgical staple close to it. A midgut volvulus secondary to a bridle in the mesenteric root was identified during surgery. Adhesiolysis and manual detorsion were performed, with adequate recovery of intestinal tissue perfusion. The free staple was not found during surgery. The patient evolved favorably and is asymptomatic and under follow-up. Although it is difficult to demonstrate a causal association, several post-appendectomy intestinal volvulus reported cases (including ours) seem related to free surgical staples in the peritoneal cavity acting as a mesenteric or intestinal anchor point. Thorough cavity cleaning after surgery, avoiding free staples, is essential to prevent this complication. A targeted computed tomography review can help identify free staples in the abdominal cavity.
Screen Culture and Literary Mythology of Mass Consciousness (two “Onegins” – 1999 and 2024)
Authors:   Saint Petersburg State University, Ilchenko Sergey
Published: December 2024

The article discusses the practice of promoting the images and meanings of classical works of Russian
literature in modern screen culture. The relevance of this topic is connected with the widespread use of images
of Russian literature in those samples of screen culture that the modern mass audience is faced with. In the
article, the method of comparative analysis will be used as the main research method. The author proposes to
compare two cinematic versions of one of the key works of Russian literature - the novel ‘Eugene Onegin’ by A.
S. Pushkin. In the course of the analysis, it is proposed to study the circumstances of the creation of both fi lms,
the cultural and socio-psychological context of the appearance of screen adaptations, and the general historical
background. Particular attention will be paid to the country of origin of each of the fi lms (Great Britain and Russia), which, of course, could not affect the fi nal result. The author examines the adequacy of screen versions,
taking into account the existing traditions of fi lm viewing and fi lm perception, determined not only by the practice
of the viewers themselves, but also by the dominant information and analytical trends characteristic of mass
communication channels, taking into account the circumstances of their functioning in each specifi c, chronological deterministic case. The author paid special attention to the principles of creating both fi lms, the factors that
formed the fi nal aesthetic solution of each of the versions - from the selection of actors to the choice of locations
and location locations. The article also touches upon the history of cinematic versions of the literary source. The
traditions of literary criticism and critical analysis of the original text by A. S. Pushkin in Russian literary criticism
are also taken into account. Attention is also paid to the distribution fate of each of the fi lms, since they were created in completely different conditions and in different systems of fi lm production with different cultural traditions
necessary for subsequent promotion to audiences.The author comes to the conclusion about the varying degree
of aesthetic adequacy of the analyzed phenomena of screen culture to the literary source, when, in his opinion,
the approach of British cinematographers is preferable.