bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of endocrine-related immune-related adverse events in Japanese subjects with various types of cancer
Authors: Iwamoto Yuichiro , Kimura Tomohiko , Iwamoto Hideyuki , Sanada Junpei , Fushimi Yoshiro , Katakura Yukino , Tatsumi Fuminori , Shimoda Masashi , Nakanishi Shuhei , Mune Tomoatsu , Kaku Kohei , Kaneto Hideaki 
Published: January 2023

BackgroundImmune checkpoint inhibitors (ICIs), such as cytotoxic T lymphocyte antigen-4 (CTLA-4) inhibitors, programmed cell death protein 1 (PD-1) inhibitors, and programmed cell death protein 1 ligand 1 (PD-L1) inhibitors, are often used to treat a variety of malignancies. ICIs are known to cause endocrine-related immune-related adverse events (irAEs), but the incidence varies among reports and/or agents. This study evaluated the incidence of endocrine-related irAEs in patients who were treated with ICIs in Japan.MethodThis single-center, retrospective, observational study examined the incidence and clinical characteristics of endocrine-related irAEs in 466 participants who were treated with ICIs at Kawasaki Medical School Hospital.ResultThe mean age of participants with and without endocrine-related irAEs was 69.1 ± 1.8 years and 68.1 ± 1.1 years, respectively, with no difference between them. The overall incidence of any endocrine-related irAEs among the participants was 25.5%. Hypothyroidism was prevalent in 24.3%, hypoadrenocorticism in 3.2%, hypopituitarism in 0.9%, and insulin-dependent diabetes mellitus in 1.1%. Participants receiving combination therapy with CTLA-4 and PD-1 inhibitors had a significantly higher incidence of endocrine-related irAEs than those receiving monotherapy.ConclusionEndocrine-related irAEs correlated significantly with survival and mean observation period. There was substantial difference in the incidence of endocrine-related irAEs among various types of ICIs and types of cancer. We should bear in mind that endocrine testing is necessary during the treatment with ICIs.
Assessment of ecosystem health based on landscape pattern in ecologically fragile regions at different spatial scales: A case study of Dianchi Lake basin, China
Authors: Lei Dongmei , Zhang Yuan , Ran Yuju , Gao Liping , Li Jie , Li Zhiguo , Mo Jinxiao , Liu Xuan 
Published: January 2023

In the process of urbanization, maintaining ecosystem health in ecologically fragile regions is an inevitable requirement for sustainable development in the future, but the ecological health status varies greatly at different spatial scales. Determining the appropriate spatial scale of ecological health assessment is the basis and premise of ecological management and environmental protection policy making. Taking Dianchi Lake basin as the research area, based on the vigor-organization-resilience (VOR) model and landscape pattern index, this study established an assessment system of ecological health to evaluate the ecosystem health status from quadrat, ecological and administrative scales, with the aim to determine a reasonable evaluation scale and strengthen regional sustainability. The results show that: 1) The suitable spatial grain of landscape pattern analysis in Dianchi Lake basin is 150 m. 2) The average values of ecosystem health indices at quadrat scale, ecological scale and administrative scale are 0.5466, 0.4977 and 0.5373, respectively, demonstrating a sub-health state. 3) The most suitable scale for ecological health assessment of Dianchi Lake basin is ecological scale, because taking sub-watershed as ecological unit can ensure the integrity of the evaluated ecosystem to the greatest extent. Multiscale assessment is helpful for eco-environmental management departments to understand the ecosystem health status at different scales and provide a scientific basis for regional eco-environmental management decisions.
Network-based quantitative trait linkage analysis of microbiome composition in inflammatory bowel disease families
Authors: Sharma Arunabh , Junge Olaf , Szymczak Silke , Rühlemann Malte Christoph , Enderle Janna , Schreiber Stefan , Laudes Matthias , Franke Andre , Lieb Wolfgang , Krawczak Michael , Dempfle Astrid 
Published: January 2023

Introduction:Inflammatory bowel disease (IBD) is characterized by a dysbiosis of the gut microbiome that results from the interaction of the constituting taxa with one another, and with the host. At the same time, host genetic variation is associated with both IBD risk and microbiome composition.Methods:In the present study, we defined quantitative traits (QTs) from modules identified in microbial co-occurrence networks to measure the inter-individual consistency of microbial abundance and subjected these QTs to a genome-wide quantitative trait locus (QTL) linkage analysis.Results:Four microbial network modules were consistently identified in two cohorts of healthy individuals, but three of the corresponding QTs differed significantly between IBD patients and unaffected individuals. The QTL linkage analysis was performed in a sub-sample of the Kiel IBD family cohort (IBD-KC), an ongoing study of 256 German families comprising 455 IBD patients and 575 first- and second-degree, non-affected relatives. The analysis revealed five chromosomal regions linked to one of three microbial module QTs, namely on chromosomes 3 (spanning 10.79 cM) and 11 (6.69 cM) for the first module, chr9 (0.13 cM) and chr16 (1.20 cM) for the second module, and chr13 (19.98 cM) for the third module. None of these loci have been implicated in a microbial phenotype before.Discussion:Our study illustrates the benefit of combining network and family-based linkage analysis to identify novel genetic drivers of microbiome composition in a specific disease context.
Autophagy-related IFNG is a prognostic and immunochemotherapeutic biomarker of COAD patients
Authors: Yue Taohua , Cai Yunlong , Zhu Jing , Liu Yucun , Chen Shanwen , Wang Pengyuan , Rong Long 
Published: January 2023

BackgroundNumerous studies have shown autophagy affects cellular immune responses. This study aims to explore prognosis and immunotherapeutic biomarkers related to autophagy in colon adenocarcinoma (COAD).MethodsBased on R software, we performed the ssGSEA, differential expression analysis, Kaplan-Meier survival analysis, correlation analysis, and enrichment analysis. For wet experiment, we did qRT-PCR, immunohistochemistry and CCK-8 experiments.ResultsUsing autophagy-related genes (ARGs) and the ssGSEA, COAD patients were divided into low and high autophagy groups. For immune score, stromal score, tumor purity, tumor infiltrating immune cells, co-signaling molecules, tumor mutational burden, microsatellite instability, mismatch repair, immune-related pathways, immune signatures, somatic mutations and subtype analysis, high autophagy group might benefit more from immunotherapy. Among 232 ARGs, IFNG was generally significantly correlated with tumor immunotherapy biomarkers (PD-L1, CD8A and cytotoxic T lymphocytes (CTL)). The disease-free survival of high IFNG group was significantly longer than that of low group. On above-mentioned immune-related research, the high IFNG group reached the same conclusion. The qRT-PCR and IHC analysis confirmed that IFNG was significantly higher expressed in dMMR samples compared to pMMR samples. For chemotherapy, the autophagy and IFNG were significantly negatively related to the chemosensitivity to cisplatin; IFNG inhibitor glucosamine increased cisplatin chemoresistance while IFNG increased cisplatin chemosensitivity; IFNG could reverse glucosamine induced chemoresistance. The functional enrichment analysis of IFNG, PD-L1, CD8A and 20 similar proteins were related to the activation of the immune system. The GSEA and ceRNA network partly described interaction mechanisms of IFNG with PD-L1 and CD8A.ConclusionAutophagy score and IFNG expression were novel immunotherapy predictive biomarkers, which might play predictive effects through the JAK-STAT signaling pathway. IFNG might be a potential targeted therapy for cisplatin resistant colon cancer. Besides, IFNG was also a prognostic indicator.
The effect of anti-PD-1/PD-L1 antibodies combined with VEGF receptor tyrosine kinase inhibitors versus bevacizumab in unresectable hepatocellular carcinoma
Authors: Zeng Hui , Xu Qi , Wang Jinyu , Xu Xiaoqing , Luo Jun , Zhang Lei , Luo Cong , Ying Jieer , Li Jingjing 
Published: January 2023

IntroductionImmune checkpoint inhibition (ICI) plus bevacizumab (BEV) is the standard first-line treatment for unresectable hepatocellular carcinoma (uHCC). We aimed to assess the efficacy and safety of ICI plus bevacizumab and ICI plus receptor tyrosine kinase inhibitor (TKI) in this patient population.MethodsThis retrospective single-institution study enrolled 94 patients with uHCC who received ICI plus TKI or bevacizumab as the first-line treatment. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR) were used to evaluate treatment efficacy. RECIST v1.1 criteria were used to calculate the objective clinical response. Common Terminology Criteria for Adverse Events were used to report and categorize adverse events.ResultsBy the last follow-up interview on May 15, 2022, there were 57 deaths, and 19 patients did not develop disease progression. Thirty patients received sintilimab/atezolizumab plus bevacizumab (ICI + BEV group), and 64 received ICI plus TKI (ICI + TKI group). The median OS was 430 days (95% CI, 266-NA) in the ICI+TKI group and 498 days (95% CI, 349-NA) in the ICI+BEV group (HR, 1.20; 95% CI, 0.69-2.07; P = 0.52). There was no significant difference between the two groups in the median PFS (182 vs. 221 days, P=0.67). In the ICI+TKI group, the ORR and DCR were 28.1% and 67.2%, respectively. In the ICI+BEV group, the ORR and DCR were 26.7% and 66.7%, respectively. The overall incidence of adverse events was similar between the two groups. Palmar-plantar erythrodysesthesia syndrome (23[36%]) occurred only in the ICI + TKI group. Patients who received ICI+BEV were more prone to upper gastrointestinal bleeding (2 [7%]), with one patient with grade 4 requiring emergency DSA treatment.ConclusionThis study found that ICI+TKI and ICI+BEV as first-line treatments were similar in OS, PFS, and tumor response in uHCC. Different populations are suitable for different regimens because of the different adverse events.
Impact of antimicrobial stewardship interventions on days of therapy and guideline adherence: A comparative point-prevalence survey assessment
Authors: Shamseddine Jinan , Sadeq Ahmed , Yousuf Khadija , Abukhater Rawan , Yahya Lamia Omer , Espil Maysaa Abdulatif , Hassan Mohamed Elamin , Fadl Rayan Elamin , Ahmed Rami Tag Elsir , Elkonaissi Islam , Abdelsalam Abeer Elmahi , Naqbi Aisha Al , Nuaimi Nora Al , Hosani Maitha Al , Marri Rowdha Al , Abdouli Asma Al , Alakhras Abdullah Mohamad , Masri Neamat Ibrahim Al , O’Sullivan Siobhan , Everett Dean , Babiker Zahir Osman Eltahir 
Published: January 2023

BackgroundAntimicrobial stewardship (AMS) is a crucial tool for rationalizing the use of antimicrobial agents and reducing the burden of antimicrobial resistance. We aimed to assess the impact of AMS interventions on antimicrobial utilization and adherence to antimicrobial guidelines.MethodsWe conducted a prospective quasi-experimental study at a major tertiary hospital in the United Arab Emirates. Using standardized World Health Organization’s methodology, point-prevalence surveys (PPS) were performed in November 2019 and January 2022. Core AMS interventions consisted of proactive bloodstream infection service, proactive and reactive infectious diseases consult service, prospective audit and feedback by clinical pharmacists, development of antimicrobial guidelines based on cumulative antibiograms, and implementation of induction programs for new clinical staff. Days of therapy (DOT) per 1000 patient days present and rate of compliance with antimicrobial guidelines were compared before and after the core interventions. Multiple logistic regression analysis was carried out to adjust for the potential confounding effects of age, gender, hospitalization within 90 days, central or peripheral line insertion, urinary catheterization, and mechanical ventilation. P-value&lt;0.05 was considered statistically significant.ResultsPre- and post-intervention PPSs included 292 and 370 patients, respectively. Both had similar age and gender distribution. Patients receiving antimicrobials were 51% (149/292) in 2019 and 45% (166/370) in 2022 (p 0.12). Univariate analysis showed a reduced post-intervention DOT per 1000 patients present (6.1 +/- 16.2 vs 2.4 +/-5.1, p&lt;0.01) and an improved post-intervention guideline compliance (59% vs 67%, p 0.23). Following multiple logistic regression, the reduction in post-intervention DOT remained statistically significant (co-efficient -0.17 (95% CI -8.58 to -1.94, p&lt;0.01), and the improvement in guideline adherence became statistically significant (adjusted odds ratio 1.91 (95% CI 1.05 to 3.45, p 0.03).ConclusionCoordinated and sustained AMS interventions have a significant impact on improving antimicrobial utilisation and adherence to guidelines.
Effect of thermal cycles on the engineering properties and durability of sustainable fibrous high-strength concrete
Authors: Hakeem Ibrahim Y. , Hosen MD. Akter , Alyami Mana , Qaidi Shaker , Özkılıç Yasin O. , Alhamami Ali , Alharthai Mohammad 
Published: January 2023

In this research, the effect of heat–cool cycles (HCCs) on high-strength concrete (HSC) containing steel fibres (SFs), polypropylene fibres (PPFs), and date palm fibres (DPFs), which were named fibrous high-strength concrete (FHSC), was studied. To produce FHSC, three doses of 0.2, 0.6, and 1 percent of each fibre were used. All samples were tested after 28 days of normal water curing and 270 days of exposure to HCCs (continuing the authors’ project and research published at 28 and 180 days). This entails heating for 2 days at 60 C in the oven and cooling for another 2 days at room temperature for 270 days. The experiment’s findings revealed that fibre reinforcement in concrete enhances its strength and durability. By incorporating the three types of fibres into high-strength concrete, with and without HCCs, the modulus of rupture was significantly increased. In both conditions, including with or without the implementation of HCCs, incorporating the three fibre types into the HSC showed a significant increase in toughness. As a result, natural date palm fibres can produce sustainable FHSC that can withstand harsh environmental conditions. Moreover, compared to the previous study conducted by the authors at 180 days, there is a slight severity in both the pattern of decrease and increase of the studied characteristics at 270 days caused by the effect of thermal cycles and fibres.
Extracutaneous features and complications of the Ehlers-Danlos syndromes: A systematic review
Authors: Doolan Brent J. , Lavallee Mark E. , Hausser Ingrid , Schubart Jane R. , Michael Pope F. , Seneviratne Suranjith L. , Winship Ingrid M. , Burrows Nigel P. 
Published: January 2023

IntroductionThe Ehlers-Danlos syndromes (EDS) comprise a group of inherited connective tissue disorders presenting with variable fragility to skin, soft tissue, and certain internal organs, which can cause significant complications, particularly arterial rupture, bowel perforation and joint difficulties. Currently, there are 14 proposed subtypes of EDS, with all except one subtype (hypermobile EDS) having an identified genetic etiology. An understanding of the extracutaneous features and complications within each subtype is key to maximizing clinical care and reducing the risk of further complications.MethodsA systematic review of EDS-related extracutaneous features and complications was undertaken.ResultsWe identified 839 EDS cases that met the inclusion criteria. We noted a high prevalence of joint hypermobility amongst kyphoscoliotic (39/39, 100%), spondylodysplastic (24/25, 96.0%), and hypermobile (153/160, 95.6%) EDS subtypes. The most common musculoskeletal complications were decreased bone density (39/43, 90.7%), joint pain (217/270, 80.4%), and hypotonia/weakness (79/140, 56.4%). Vascular EDS presented with cerebrovascular events (25/153, 16.3%), aneurysm (77/245, 31.4%), arterial dissection/rupture (89/250, 35.5%), and pneumothorax/hemothorax. Chronic pain was the most common miscellaneous complication, disproportionately affecting hypermobile EDS patients (139/157, 88.5%). Hypermobile EDS cases also presented with chronic fatigue (61/63, 96.8%) and gastrointestinal complications (57/63, 90.5%). Neuropsychiatric complications were noted in almost all subtypes.DiscussionUnderstanding the extracutaneous features and complications of each EDS subtype may help diagnose and treat EDS prior to the development of substantial comorbidities and/or additional complications.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022308151, identifier CRD42022308151.
Anammox bacterial abundance and diversity in different temperatures of purple paddy soils by 13C-DNA stable-isotope probing combined with high-throughput sequencing
Authors: Yu Zijie , He Xinhua , Li Zhitong , Zhou Shuang , Guo Dalu , Pu Hao , Luo Hongyan 
Published: January 2023

IntroductionAnaerobic ammonium oxidation (anammox) plays a vital role in the global nitrogen cycle by oxidizing ammonium to nitrogen under anaerobic environments. However, the existence, abundance, and diversity of anammox bacteria between different temperatures are less studied, particularly in purple paddy soils.Methods13C-DNA stable-isotope probe combined with Illumina MiSeq high-throughput sequencing was employed to explore soil abundance and diversity of anammox bacteria. In doing so, 40–60 cm depth soils from typical purple paddy soils in Chongqing, southwest China, were cultured under 12CO2-labeled and 13CO2-labeled at 35°C, 25°C, 15°C, and 5°C for 56 days.Results and DiscussionAnammox bacteria were not labeled at all by 13CO2 at 5°C. The highest abundance of anammox bacteria was found at 25°C (3.52 × 106~3.66 × 106 copies·g−1 dry soil), followed by 35°C and 15°C (2.01 × 106~2.37 × 106 copies·g−1 dry soil) and almost no increase at 5°C. The relative abundance of Candidatus Jettenia sp. was higher at 25°C and 15°C, while Candidatus Brocadia sp. was higher at 35°C and 5°C. Our results revealed differences in anammox bacteria at different temperatures in purple paddy soils, which could provide a better understanding of soil N cycling regulated by anammox bacteria.
Effect of transcranial direct current stimulation for patients with disorders of consciousness: A systematic review and meta-analysis
Authors: Ma Hui , Zhao Kehong , Jia Chengsen , You Jiuhong , Zhou Mei , Wang Tingting , Huang Cheng 
Published: January 2023

IntroductionTranscranial direct current stimulation (tDCS) could potentially facilitate consciousness improvement in patients with disorders of consciousness (DOC). The aim of this study was to investigate the therapeutic efficacy of tDCS on consciousness recovery for patients with DOC.MethodsEight databases were systematically searched from their inception to June 2022. Quality of included studies were assessed using PEDro score and Cochrane’s risk of bias assessment. All statistical analyses were performed using RevMan software. Seventeen studies with 618 patients were identified eligible for this study, and fifteen studies with sufficient data were pooled in the meta-analysis.ResultsThe results of meta-analysis showed a significant effect on increasing GCS scores (MD = 1.73; 95% CI, 1.28–2.18; P &lt; 0.01) and CRS-R scores (MD = 1.28; 95% CI = 0.56–2.00; P &lt; 0.01) in favor of the real stimulation group as compared to sham. The results of subgroup analysis demonstrated that only more than 20 sessions of stimulation could significantly enhance the improvement of GCS scores and the CRS-R scores. Moreover, the effect of tDCS on CRS-R score improvement was predominant in patients with minimal conscious state (MCS) (MD = 1.84; 95% CI = 0.74–2.93; P &lt; 0.01).ConclusionAnodal tDCS with sufficient stimulation doses appears to be an effective approach for patients with MCS, in terms of CRS-R scores.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022336958.
Strategies for five tumour markers in the screening and diagnosis of female breast cancer
Authors: Luo Jun , Xiao Jianbo , Yang Yuwei , Chen Gang , Hu Dong , Zeng Jiawei 
Published: January 2023

ObjectiveThis study evaluated the diagnostic value of different combinations of five commonly used tumour markers and screened the best combination of tumour markers.MethodsRegression analysis was used to evaluate 185 patients with suspected breast cancer admitted to Mianyang Central Hospital from January 2020 to December 2021. The differences of five tumour markers between a breast cancer group and a benign lesion group were analysed. The sensitivity and specificity of five tumour markers were compared.ResultsOf 185 patients with suspected breast cancer, 108 patients had breast cancer and 77 patients had benign breast tumours. The detection results of carcinoembryonic antigen (CEA), alpha fetoprotein (AFP), carbohydrate antigen 125 (CA125), carbohydrate antigen 199 (CA199) and carbohydrate antigen 153 (CA153) in patients with breast cancer were significantly higher than those in patients with benign breast tumours. In the analysis of the single-detection results of tumour markers, CEA had the highest sensitivity (23.94%), CA153 had the highest specificity (96.43%), AFP had the highest accuracy (47.66%) and CA153 had the highest area under the curve (AUC) value (0.727). With the increase of parallel indicators, the sensitivity, accuracy and AUC value increased in turn, and the increase was obvious in the front. The increase began to slow down after the three parallel indicators. Among the different combinations of three parallel detections of breast cancer tumour markers, the highest sensitivity was AFP + CEA + CA153 (83.46%), the highest accuracy was AFP + CEA + CA153 and AFP + CA153 + CA125 (80.25%), and the highest AUC was CEA + CA125 + CA199 (0.922).ConclusionAFP, CA153 and CA199 are recommended for clinical diagnosis of breast cancer. In routine physical examination and early breast cancer screening, the optimal combination of AFP + CEA + CA153 three parallel tests is recommended.
Reconstructive types effect the prognosis of patients with tumors in the central and nipple portion of breast cancer? An analysis based on SEER database
Authors: Wang Ping , Wang Le , Liang Xiaming , Si Erran , Yang Yongguang , Kong Lingfei , Dong Yonghui 
Published: January 2023

IntroductionThe impact of different types of reconstruction, including tissue reconstruction, implant reconstruction and combined reconstruction, on patient survival were not illustrated completely. We tried to investigate the impact of patient survival between different types of reconstruction.MethodsWe enrolled 6271 patients with tumors in the central and nipple portion of breast cancer from the Surveillance, Epidemiology, and End Results database. Factors associated with survival were identified by Cox regression analyses. The mortality rates per 1,000 person-years were calculated and compared. Survival curves were produced by Kaplan-Meier analyses using log-rank tests and cox proportional hazards regression quantified the risk of survival.ResultsReconstructive types, region, insurance, race, marial status, grade, stage, ER status, PR status, HER-2 status and chemotherapy were significant prognostic factors associated with breast cancer-specific survival. The breast cancer mortality rates per 1,000 person-years for patients with tissue, implant and combined group were 26.01,21.54 and 19.83 which showed a downward trend. The HR of implant and combined reconstruction adjusted for demographic, pathological, and therapeutic data was 0.82 (95% CI: 0.67-1.00, p=0.052) and 0.73(95% CI:0.55-0.97, p=0.03) compared with tissue reconstruction.ConclusionBreast cancer-related mortality between implant reconstruction and autologous tissue reconstruction showed no significantly different, but the risk of BCSS of compound reconstruction was lower than tissue reconstruction.