bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Glycemic Variability Evaluated by Continuous Glucose Monitoring is Associated with Osteoporosis in Type 2 Diabetic Patients
Authors: Huang Rong , Wang Huiying , Shen Ziyang , Cai Tingting , Zhou Yunting , Wang Yuming , Xia Wenqing , Ding Bo , Yan Rengna , Li Huiqin , Wu Jindan , Ma Jianhua 
Published: June 2022

BackgroundSubjects with type 2 diabetes mellitus (T2DM) are susceptible to osteoporosis. This study was conducted to evaluate the association between glycemic variability evaluated by continuous glucose monitoring (CGM) and osteoporosis in type 2 diabetic patient.MethodsA total of 362 type 2 diabetic subjects who underwent bone mineral density (BMD) measurement and were monitored by a CGM system from Jan 2019 to May 2020 were enrolled in this cross-sectional study. Glycemic variability was calculated with the Easy GV software, including 24-hour mean blood glucose (24-h MBG), the standard deviation of 24-h MBG (SDBG), coefficient of variation (CV), mean amplitude of glycemic excursions (MAGE), and time in range between 3.9 and 10.0 mmol/L (TIR). Other potential influence factors for osteoporosis were also examined.ResultsBased on the T-scores of BMD measurement, there were 190 patients with normal bone mass, 132 patients with osteopenia and 40 patients with osteoporosis. T2DM patients with osteoporosis showed a higher 24-h MBG, SDBG, CV, and MAGE, but a lower TIR (all p &lt; 0.05). Multivariate logistic regression analysis revealed that age, female gender, body mass index (BMI), low-density lipoprotein cholesterol (LDL-C), serum uric acid (SUA) and MAGE independently contribute to osteoporosis, and corresponding odds ratio [95% confidence interval (CI)] was 1.129 (1.072-1.190), 4.215 (1.613-11.012), 0.801 (0.712-0.901), 2.743 (1.385-5.431), 0.993 (0.988-0.999), and 1.380 (1.026-1.857), respectively. Further receiver operating characteristic analysis with Youden index indicated that the area under the curve and its 95% CI were 0.673 and 0.604-0.742, with the optimal cut-off value of MAGE predicting osteoporosis being 4.31 mmol/L.ConclusionIn addition to conventional influence factors including age, female gender, BMI, LDL-C and SUA, increased glycemic variability assessed by MAGE is associated with osteoporosis in type 2 diabetic patients.
Identification of Tumor Antigens and Immune Subtypes of Esophageal Squamous Cell Carcinoma for mRNA Vaccine Development
Authors: Lu Tong , Xu Ran , Wang Cheng-Hao , Zhao Jia-Ying , Peng Bo , Wang Jun , Zhang Lin-You 
Published: June 2022

Purpose: The applicability of mRNA vaccines against esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we identified potential antigens for developing mRNA vaccines against ESCC and characterized immune subtypes to select appropriate patients for vaccination.Methods: RNA-seq, genetic alteration data, and corresponding clinical information of ESCC patients were obtained from the Cancer Genome Atlas (TCGA) database. The RNA-seq data of normal esophageal tissue were obtained from the Genotype-Tissue Expression (GTEx) database. Potential tumor antigens were screened by analyzing differentially expressed and mutated genes and potential antigens with significant differences in prognosis were screened using the Kaplan-Meier method. The proportion of immune cell infiltration in the tumor microenvironment was estimated using CIBERSORT and MCPcounter, and the correlation of potential antigens with antigen-presenting cells and major histocompatibility complex class II was analyzed. Subsequently, immune subtypes were constructed using consensus clustering analysis and characterized by single-sample gene set enrichment analysis and weighted gene co-expression network analysis (WGCNA). The Genomics of Drug Sensitivity in Cancer (GDSC) database was used to analyze the drug sensitivity of different immune subtypes.Results: Four overexpressed and mutated tumor antigens associated with antigen presentation and poor prognosis were identified in ESCC, including NLRC5, FCRL4, TMEM229B, and LCP2. By consensus clustering, we identified two immune-associated ESCC subtypes, immune subtype 1 (IS1) and immune subtype 2 (IS2); the prognosis of the two subtypes was statistically different. In addition, the two immune subtypes had distinctly different cellular, molecular, and clinical characteristics. IS1 patients have a distinct immune “hot” phenotype with strong immune tolerance, whereas patients with IS2 have an immune “cold” phenotype. Differential expression of immune checkpoints and immunogenic cell death modulators was observed between the different immune subtypes. Finally, we found that IS1 and IS2 patients showed different drug sensitivities to common anti-tumor drugs, possibly facilitating the development of individualized treatment regimens for patients.Conclusion: NLRC5, LCP2, TMEM229B, and FCRL4 are potential antigens for ESCC mRNA vaccines, and such vaccines may be more suitable for IS2 patients. This study provides a theoretical basis for mRNA vaccines against ESCC, by identifying the critical characteristics to predict ESCC prognosis and select suitable patients for vaccination.
Clinical Benefits of Olaparib in Mexican Ovarian Cancer Patients With Founder Mutation BRCA1-Del ex9-12
Authors: Gallardo-Rincón Dolores , Montes-Servín Edgar , Alamilla-García Gabriela , Montes-Servín Elizabeth , Bahena-González Antonio , Cetina-Pérez Lucely , Morales Vásquez Flavia , Cano-Blanco Claudia , Coronel-Martínez Jaime , González-Ibarra Ernesto , Espinosa-Romero Raquel , María Alvarez-Gómez Rosa , Pedroza-Torres Abraham , Castro-Eguiluz Denisse 
Published: June 2022

Background: Ovarian cancer (OC) is gynecologic cancer with the highest mortality rate. It is estimated that 13–17% of ovarian cancers are due to heritable mutations in BRCA1 and BRCA2. The BRCA1 (BRCA1-Del ex9-12) Mexican founder mutation is responsible for 28–35% of the cases with ovarian cancer. The aim was to describe the PFS of OC patients treated with olaparib, emphasizing patients carrying the Mexican founder mutation (BRCA1-Del ex9-12).Methods: In this observational study, of 107 patients with BRCAm, 35 patients were treated with olaparib from November 2016 to May 2021 at the Ovarian Cancer Program (COE) of Mexico; patient information was extracted from electronic medical records.Results: Of 311 patients, 107 (34.4%) were with BRCAm; 71.9% (77/107) were with BRCA1, of which 27.3% (21/77) were with BRCA1-Del ex9-12, and 28.1% (30/107) were with BRCA2 mutations. Only 35 patients received olaparib treatment, and the median follow-up was 12.87 months. The PFS of BRCA1-Del ex9-12 was NR (non-reach); however, 73% of the patients received the treatment at 36 vs. 11.59 months (95% CI; 10.43–12.75) in patients with other BRCAm (p = 0.008). Almost 50% of patients required dose reduction due to toxicity; the most frequent adverse events were hematological in 76.5% and gastrointestinal in 4%.Conclusion: Mexican OC BRCA1-Del ex9-12 patients treated with olaparib had a significant increase in PFS regardless of the line of treatment compared to other mutations in BRCA.
Outcomes of Care by Geriatricians and Non-geriatricians in an Academic Hospital
Authors: Merchant Reshma Aziz , Ho Vanda Wen Teng , Chen Matthew Zhixuan , Wong Beatrix Ling Ling , Lim Zhiying , Chan Yiong Huak , Ling Natalie , Ng Shu Ee , Santosa Amelia , Murphy Diarmuid , Vathsala Anantharaman 
Published: June 2022

IntroductionWhile hospitalist and internist inpatient care models dominate the landscape in many countries, geriatricians and internists are at the frontlines managing hospitalized older adults in countries such as Singapore and the United Kingdom. The primary aim of this study was to determine outcomes for older patients cared for by geriatricians compared with non-geriatrician-led care teams.Materials and MethodsA retrospective cohort study of 1,486 Internal Medicine patients aged ≥75 years admitted between April and September 2021 was conducted. They were either under geriatrician or non-geriatrician (internists or specialty physicians) care. Data on demographics, primary diagnosis, comorbidities, mortality, readmission rate, Hospital Frailty Risk Score (HFRS), Age-adjusted Charlson Comorbidity Index, Length of Stay (LOS), and cost of hospital stay were obtained from the hospital database and analyzed.ResultsThe mean age of patients was 84.0 ± 6.3 years, 860 (57.9%) females, 1,183 (79.6%) of Chinese ethnicity, and 902 (60.7%) under the care of geriatricians. Patients under geriatrician were significantly older and had a higher prevalence of frailty, dementia, and stroke, whereas patients under non-geriatrician had a higher prevalence of diabetes and hypertension. Delirium as the primary diagnosis was significantly higher among patients under geriatrician care. Geriatrician-led care model was associated with shorter LOS, lower cost, similar inpatient mortality, and 30-day readmission rates. LOS and cost were lower for patients under geriatrician care regardless of frailty status but significant only for low and intermediate frailty groups. Geriatrician-led care was associated with significantly lower extended hospital stay (OR 0.73; 95% CI 0.56–0.95) and extended cost (OR 0.69; 95% CI 0.54–0.95).ConclusionGeriatrician-led care model showed shorter LOS, lower cost, and was associated with lower odds of extended LOS and cost.
Cross-Talk Between the Intestinal Epithelium and Salmonella Typhimurium
Authors: Ménard Sandrine , Lacroix-Lamandé Sonia , Ehrhardt Katrin , Yan Jin , Grassl Guntram A. , Wiedemann Agnès 
Published: June 2022

Salmonella entericaserovars are invasive gram-negative bacteria, causing a wide range of diseases from gastroenteritis to typhoid fever, representing a public health threat around the world.Salmonellagains access to the intestinal lumen after oral ingestion of contaminated food or water. The crucial initial step to establish infection is the interaction with the intestinal epithelium. Human-adapted serovars such asS.Typhi orS.Paratyphi disseminate to systemic organs and induce life-threatening disease known as typhoid fever, whereas broad-host serovars such asS.Typhimurium usually are limited to the intestine and responsible for gastroenteritis in humans. To overcome intestinal epithelial barrier,Salmonelladeveloped mechanisms to induce cellular invasion, intracellular replication and to face host defence mechanisms. Depending on the serovar and the respective host organism, disease symptoms differ and are linked to the ability of the bacteria to manipulate the epithelial barrier for its own profit and cross the intestinal epithelium.This review will focus onS.Typhimurium (STm). To better understand STm pathogenesis, it is crucial to characterize the crosstalk between STm and the intestinal epithelium and decipher the mechanisms and epithelial cell types involved. Thus, the purpose of this review is to summarize our current knowledge on the molecular dialogue between STm and the various cell types constituting the intestinal epithelium with a focus on the mechanisms developed by STm to cross the intestinal epithelium and access to subepithelial or systemic sites and survive host defense mechanisms.
Comparison of Oncologic Outcomes Between Incomplete Obstructive Colon Cancer and Non-Obstructive Colon Cancer by Tumor Location
Authors: Lim Ji Ha , Lee Woo Yong , Yun Seong Hyeon , Kim Hee Cheol , Cho Yong Beom , Huh Jung Wook , Park Yoon Ah , Shin Jung Kyong 
Published: June 2022

IntroductionObstruction in colon cancer is a well-known risk factor for worse oncologic outcomes. However, studies on differences in survival of patients with incomplete obstructive colon cancer (IOCC) by tumor location are insufficient. Thus, the aim of this study was to compare oncologic outcomes between IOCC and non-obstructive colon cancer (NOCC) according to tumor location.MethodsFrom January 2010 to December 2015, a total of 2,004 patients diagnosed with stage II or stage III colon adenocarcinoma who underwent elective colectomy were included (IOCC, n = 405; NOCC, n = 1,599). Incomplete obstruction was defined as a state in which colonoscopy could not pass through the cancer lesion but did not require emergent surgery, stent insertion, or stoma formation because the patient was asymptomatic without problem in bowel preparation. Kaplan–Meier method and log-rank tests were used to compare survival between IOCC and NOCC. Multivariable analysis was performed to determine which factors affected survivals.ResultsStage III IOCC patients showed significantly lower overall survival (OS) and recurrence-free survival (RFS). Stage II IOCC patients and stage III NOCC patients had similar survival curves. IOCC patients with tumors on the right side showed worse OS than other patients. In multivariable analysis, incomplete obstruction was an independent risk factor for worse OS and RFS in all stages. Tumor located at the right side in stage III was an independent risk factor for RFS (HR: 1.40, p = 0.030).ConclusionsPatients with IOCC showed significantly worse survival outcomes than those with NOCC. Stage II IOCC patients and stage III NOCC patients showed similar survival. Patients with stage III IOCC located at the right side showed significantly worse oncologic outcomes than those located at the left side. These results confirm that prognosis is different depending on the presence of incomplete obstruction and the location of the tumor, even in the same stage.
Myeloid-Derived Suppressor Cells and Clinical Outcomes in Children With COVID-19
Authors: Bline Katherine , Andrews Angel , Moore-Clingenpeel Melissa , Mertz Sara , Ye Fang , Best Victoria , Sayegh Rouba , Tomatis-Souverbielle Cristina , Quintero Ana M. , Maynard Zachary , Glowinski Rebecca , Mejias Asuncion , Ramilo Octavio 
Published: June 2022

BackgroundAlthough children with COVID-19 account for fewer hospitalizations than adults, many develop severe disease requiring intensive care treatment. Critical illness due to COVID-19 has been associated with lymphopenia and functional immune suppression. Myeloid-derived suppressor cells (MDSCs) potently suppress T cells and are significantly increased in adults with severe COVID-19. The role of MDSCs in the immune response of children with COVID-19 is unknown.AimsWe hypothesized that children with severe COVID-19 will have expansion of MDSC populations compared to those with milder disease, and that higher proportions of MDSCs will correlate with clinical outcomes.MethodsWe conducted a prospective, observational study on a convenience sample of children hospitalized with PCR-confirmed COVID-19 and pre-pandemic, uninfected healthy controls (HC). Blood samples were obtained within 48 h of admission and analyzed for MDSCs, T cells, and natural killer (NK) cells by flow cytometry. Demographic information and clinical outcomes were obtained from the electronic medical record and a dedicated survey built for this study.ResultsFifty children admitted to the hospital were enrolled; 28 diagnosed with symptomatic COVID-19 (10 requiring ICU admission) and 22 detected by universal screening (6 requiring ICU admission). We found that children with severe COVID-19 had a significantly higher percentage of MDSCs than those admitted to the ward and uninfected healthy controls. Increased percentages of MDSCs in peripheral blood mononuclear cells (PBMC) were associated with CD4+ T cell lymphopenia. MDSC expansion was associated with longer hospitalizations and need for respiratory support in children admitted with acute COVID-19.ConclusionThese findings suggest that MDSCs are part of the dysregulated immune responses observed in children with severe COVID-19 and may play a role in disease pathogenesis. Future mechanistic studies are required to further understand the function of MDSCs in the setting of SARS-CoV-2 infection in children.
Real-World Data and Budget Impact Analysis (BIA): Evaluation of a Targeted Next-Generation Sequencing Diagnostic Approach in Two Orthopedic Rare Diseases
Authors: Pedrini Elena , Negro Antonella , Di Brino Eugenio , Pecoraro Valentina , Sculco Camilla , Abelli Elisabetta , Gnoli Maria , Magrelli Armando , Sangiorgi Luca , Cicchetti Americo 
Published: June 2022

Objective: Next-generation sequencing (NGS) technology, changing the diagnostic approach, has become essential in clinical settings, and its adoption by public health laboratories is now the practice. Despite this, as technological innovations, its intake requires an evaluation of both the clinical utility and the economic investment, especially considering the rare disease scenario. This study evaluated the analytical validity and the budget impact of an NGS-Ion Torrent™ approach for the molecular germline diagnosis of two musculoskeletal rare diseases.Methods: Two cohorts of 200 and 199 patients with suspect or clinical diagnosis of multiple osteochondromas (MO) and osteogenesis imperfecta (OI) previously evaluated with a single-gene diagnostic protocol were re-analyzed using a targeted NGS assay. Analytical validity was assessed by comparing NGS and single-gene protocol. A budget impact analysis using real-world cost data-considering the healthcare perspective— was performed by applying activity-based costing (ABC). The cost considered consumables, personnel, and equipment. Additional costs not related to NGS activities were not considered. Sensitivity analysis was performed.Results: The NGS method showed a higher (for MO) and comparable (for OI) diagnostic sensitivity than the traditional techniques, apart from always reducing the time and costs of diagnosis. Overall, the cost saving per patient is € 765 for OI and € 74 for MO. Materials represented the highest cost driver of the NGS process. A time saving—proportional to the panel size—has been assessed in both cases.Conclusions: Our targeted NGS diagnostic approach decreases time to diagnosis and costs, appearing to be beneficial and recommended both for patients and from a healthcare perspective in routine diagnosis also considering very small gene panels and a low patient flow. The adequate analytical sensitivity always required the additional Sanger sequencing step of the low- and non-covered regions. A more accurate strategy evaluation is suggested in the case of ultra-rare/complex diseases, large gene-panel, or non-reference diagnostic centers.
Homologous Recombination Pathway Alternation Predicts Prognosis of Colorectal Cancer With Chemotherapy
Authors: Lin Yan , Liao Xiaoli , Zhang Yumei , Wu Guobin , Ye Jiazhou , Luo Shanshan , He Xinxin , Luo Min , Xie Mingzhi , Zhang Jinyan , Li Qian , Huang Yu , Liao Sina , Li Yongqiang , Liang Rong 
Published: June 2022

Background: Chemotherapy is the basic treatment for colorectal cancer (CRC). However, colorectal cancer cells often develop resistance to chemotherapy drugs, leading to recurrence and poor prognosis. More and more studies have shown that the Homologous recombination (HR) pathway plays an important role in chemotherapy treatment for tumors. However, the relationship between HR pathway, chemotherapy sensitivity, and the prognosis of CRC patients is still unclear.Methods: We collected 35 samples of CRC patients after chemotherapy treatment from Guangxi Medical University Cancer Hospital, then collected mutation data and clinical prognosis data from the group. We also downloaded Mondaca-CRC, TCGA-CRC cohorts for chemotherapy treatment.Result: We found that HR mutant-type (HR-MUT) patients are less likely to experience tumor metastasis after receiving chemotherapy. Additionally, our univariate and multivariate cox regression models showed that HR-MUT can be used as an independent predictor of the prognosis of chemotherapy for CRC patients. The KM curve showed that patients with HR-MUT CRC had significantly prolonged overall survival (OS) time (log-rank p = 0.017; hazard ratio (HR) = 0.69). Compared to HR mutant-type (HR-WT), HR-MUT has a significantly lower IC50 value with several chemotherapeutic drugs. Pathway enrichment analysis further revealed that the HR-MUT displayed a significantly lower rate of DNA damage repair ability, tumor growth, metastasis activity, and tumor fatty acid metabolism activity than HR-WT, though its immune response activity was notably higher.Conclusion: These findings indicate that HR-MUT may be a relevant marker for CRC patients receiving chemotherapy, as it is closely related to improving OS time and reducing chemotherapy resistance.
Sociodemographic Determinants of Willingness and Extent to Pay for COVID-19 Vaccine in India
Authors: Kiran Tanvi , Junaid K. P. , Sharma Divya , Jain Lovely , Vij Jatina , Satapathy Prakasini , Chakrapani Venkatesan , Patro Binod Kumar , Kar Sitanshu Sekhar , Singh Ritesh , Pala Star , Bali Surya , Rustagi Neeti , Goel Kapil , Sankhe Lalit , Modi Bhavesh , Gupta Madhu , Aggarwal Arun Kumar , Rajagopal Vineeth , Padhi Bijaya Kumar 
Published: June 2022

BackgroundResponding to the fast transmission rates and increasing fatality rates, countries across the world expedited the development and deployment of the vaccine for coronavirus disease 2019 (COVID-19). Evaluation of individuals' willingness to pay (WTP) would provide pertinent information regarding future demand and financing preferences, which shall help to devise the effective payment strategy for COVID-19 vaccination.MethodsA nationwide, cross-sectional, and self-administered online survey using a structured questionnaire was conducted to identify the sociodemographic determinants of willingness and extent to pay for COVID-19 vaccine in India. A non-probability convenience sampling followed by snowball sampling was employed to recruit participants (n = 3,341). The likelihood of sociodemographic determinants to predict willingness and extent to pay was modeled using the multivariate binary logistic regression analysis.ResultsOut of 3,341 participants, 68% (n = 2,271) were willingness to pay for COVID-19 vaccine. Results showed significantly higher odds for willingness to pay among participants who were single [adjusted odds ratio (aOR) = 1.394, p &lt; 0.01] and having a family size of 4 members (aOR = 1.346, p &lt; 0.01). The adjusted odds ratio sizably increased from 1.396 for participants whose monthly income was between INR 10,000 and 20,000/month to 2.240 for participants whose monthly income was above INR 50,000/month. Further, out of 2,271 of those participants who were willingness to pay for COVID-19 vaccine, majority (n = 1,246, 54.9%) of participants were willingness to pay below 50% of COVID-19 vaccine cost. This study found that those who are single (aOR = 0.688, p &lt; 0.01), having an income between INR 20,000 and 50,000/month (aOR = 0.686, p &lt; 0.05), and those who belonged to socially disadvantaged category (aOR = 0.450, p &lt; 0.01) were estimated to have significantly lower odds of willingness to pay more than 50% of COVID-19 vaccine cost.ConclusionThis study observed that majority of those participants who willingness to pay for COVID-19 vaccine were willingness to pay only up to 50% of COVID-19 vaccine and income was observed as a precursor predictor of the willingness and extent to pay for COVID-19 vaccine. The understanding on the willingness and extent to pay for COVID-19 vaccine and its sociodemographic determinants will be helpful for making the strategic decisions related to the financing of COVID vaccine in India.