bluuebunny/crossref_metadata_2025_split huggingface dataset:
Baseline Testosterone Predicts Body Composition and Metabolic Response to Testosterone Therapy
Authors: Deepika FNU , Ballato Elliot , Colleluori Georgia , Aguirre Lina , Chen Rui , Qualls Clifford , Villareal Dennis T. , Armamento-Villareal Reina 
Published: July 2022

ContextMale hypogonadism adversely affects body composition, bone mineral density (BMD), and metabolic health. A previous report showed that pre-treatment testosterone (T) levels of &lt;200 ng/dl is associated with greater improvement in spine BMD with T therapy. However, to date, there is no study that investigates whether baseline T levels also influence body composition and metabolic response to T therapy.ObjectiveThe aim of this study is to determine if there are differences in the changes in body composition, metabolic profile, and bone turnover markers, in addition to BMD, in response to T therapy in men with a baseline T level of &lt;264 ng/dl compared to those with levels ≥264 ng/dl.MethodsThis is a secondary analysis of a single-arm, open-label clinical trial (NCT01378299) on pharmacogenetics of response to T therapy conducted between 2011 and 2016 involving 105 men (40–74 years old), with average morning T &lt; 300 ng/dl, given intramuscular T cypionate 200 mg every 2 weeks for 18 months. Subjects were divided into those with baseline T levels of &lt;264 ng/dl (N = 43) and those with ≥264 ng/dl (N = 57). T and estradiol (E2) were measured by liquid chromatography/mass spectrometry; serum bone turnover markers (C-telopeptide [CTX], osteocalcin, and sclerostin), adiponectin, and leptin were measured by enzyme-linked immunosorbent assay; glycated hemoglobin (HbA1c) was measured by high-performance liquid chromatography; and areal BMD and body composition was measured by dual-energy x-ray absorptiometry (DXA).ResultsMen with T &lt; 264 ng/dl showed greater increases in total fat-free mass (FFM) at 18 months compared to those with T ≥ 264 ng/dl (4.2 ± 4.1 vs. 2.7 ± 3.8%; p = 0.047) and unadjusted appendicular FFM at 6 and 18 months (8.7 ± 11.5 vs. 4.4 ± 4.3%, 7.3 ± 11.6 vs. 2.4 ± 6.8%; p = 0.033 and p = 0.043, respectively). Men with T ≥ 264 ng/dl showed significant decreases in HbA1c at 12 months (−3.1 ± 9.2 vs. 3.2 ± 13.9%; p = 0.005), fasting glucose at 18 months (−4.2 ± 31.9 vs. 13.0 ± 57.3%; p = 0.040), LDL at 6 months (−6.4 ± 27.5 vs. 12.8 ± 44.1%; p = 0.034), and leptin at 18 months (−40.2 ± 35.1 vs. −27.6 ± 31.0%; p = 0.034) compared to those with T &lt; 264 ng/dl. No significant differences in BMD and bone turnover markers were observed.ConclusionT therapy results in improvement in body composition irrespective of baseline T levels but T &lt; 264 ng/dl is associated with greater improvement in FFM, whereas a T level of ≥264 ng/dl favors improvement in metabolic profile.
An Elevated METS-IR Index Is Associated With Higher Asthma Morbidity and Earlier Age of First Asthma in US Adults: Results Based on a Cross-Sectional Study
Authors: Chen Yan , Yang Junping , Han Kexing , Wang Yan , Zhuang Cuixia , Zhu Laxiang , Chen Mingwei 
Published: July 2022

ObjectiveThe purpose of this study was to evaluate whether there is a correlation between the METS-IR index and asthma among Americans.MethodsIn an attempt to establish the relationship between the METS-IR index and asthma prevalence and age at first onset of asthma, we conducted a logistic regression analysis, subgroup analysis, and dose-response curve analysis using the National Health and Nutrition Examination Survey (NHANES) database.ResultsIn model 3, each unit increase in METS-IR index led to 1.5% increase in asthma prevalence (OR= 1.015, 95% CI: 1.012, 1.018) and an earlier age of onset of asthma by 0.057years (β= -0.057, 95% CI: -0.112, -0.002).Stratified analysis determined that an increase in METS-IR index was associated with asthma prevalence in almost all subgroups, except in the group where it was not known whether a blood relative had asthma, and a positive linear relationship was found between METS-IR index and asthma prevalence, as well as a linear negative relationship with age at asthma onset.ConclusionDespite the fact that a direct causal relationship cannot be demonstrated, a higher METS-IR index is positively related to asthma prevalence and correspondingly may result in asthma onset at younger ages.
Addition of Capecitabine to Adjuvant Chemotherapy May be the Most Effective Strategy for Patients With Early-Stage Triple-Negative Breast Cancer: A Network Meta-Analysis of 9 Randomized Controlled Trials
Authors: Li Zhiyang , Zheng Jiehua , Ji Zeqi , Chen Lingzhi , Wu Jinyao , Zou Juan , Liu Yiyuan , Lin Weixun , Cai Jiehui , Chen Yaokun , Chen Yexi , Lu Hai 
Published: July 2022

Background and ObjectivePrevious studies determined the therapeutic effects of capecitabine-based chemotherapy regimens on early-stage triple-negative breast cancer (TNBC). However, the optimal strategy of capecitabine-based chemotherapy remains uncertain. We conducted this network meta-analysis to address this issue.MethodsWe systematically searched PubMed, Embase, and the Cochrane Registry of Controlled Trials (CENTRAL) to retrieve eligible studies published before September 2021. Two independent reviewers extracted information from eligible studies using a pre-designed data extraction sheet. The primary outcome included disease-free survival, and the second outcome showed overall survival and adverse events. Direct meta-analysis was performed using RevMan 5.4, and Bayesian network analysis was performed using R version 3.6.1 with the “gemtc” and “rjags” packages.ResultsNine studies involving 3661 TNBC patients met the selection criteria. The network meta-analysis suggested that the addition of capecitabine to adjuvant chemotherapy achieved a significantly longer disease-free (HR = 0.66, 95% CrI = 0.49 to 0.86) and overall survival time (HR = 0.60, 95% CrI = 0.43 to 0.83) than standard chemotherapy. All comparisons did not achieve statistical significance. The addition of capecitabine to adjuvant chemotherapy was the most effective treatment for improving disease-free (81.24%) and overall survival (78.46%) times, and the replacement of capecitabine to adjuvant chemotherapy was the safest regime.ConclusionsBased on available evidence, capecitabine-based chemotherapy benefits TNBC patients, and the addition of capecitabine with adjuvant chemotherapy was the most effective regime. In contrast, the replacement of capecitabine to adjuvant chemotherapy was the safest regime. More studies of high quality and large scale are needed to confirm our findings.
Evolution of the Anthropogenic Gallium Cycle in China From 2005 to 2020
Authors: Jia Hongxiang , Zhou Yanjing , Wang Anjian , Wang Gaoshang , Li Tianjiao , Wang Chunhui , Xing Wanli , Ma Zhe , Li Pengyuan 
Published: July 2022

Gallium is deemed to be a critical mineral given its irreplaceable use in consumer electronics and clean energy technologies. China has become a significant consumer of gallium while also playing a leading role in global gallium production, accounting for more than 90% of the world’s primary output in recent years. However, the quantification and evolution of China’s gallium cycle is limited until now. This study aims to uncover the dynamic flows and stocks of gallium in China during the period of 2005–2020. The results reveal that: 1) From 2005 to 2020, China’s gallium demand increased more than 20-fold, as a result of the booming semiconductor industry and the surging use of gallium in some low-carbon technologies; 2) despite the inefficient recovery issues existed in the production stage, the supply of gallium extracted as a byproduct grew in tandem with the capacity of alumina production, resulting in a significant supply surplus of 948 t by 2020; 3) China exported nearly half of its gallium mainly as raw materials and final products, but still experienced a high reliance on imported gallium-containing intermediate products from abroad, such as integrated circuits; 4) the generations of in-use stocks and end-of-life flows of gallium have accelerated since 2005 and reached about 278 t and 169 t in 2020, respectively. These indicate a large amount of available secondary gallium resource, with nonexistent recycling. The results provide a basis for identifying gallium extraction, use, loss and recycling within its anthropogenic cycle in China, as well as guidance for stakeholders to make future decisions concerning ways to improve resource efficiency and promote sustainable gallium practices from a dynamic material cycle perspective.
Impacts on Meteorological Parameters and Pollutants by Aerosol Direct Radiative Effect Over Tianjin, China
Authors: Hao Jian , Cai Ziying , Han Suqin , Ma Gengxue , Zhang Min , Qiu Xiaobin 
Published: July 2022

The direct radiative effect (DRE) of anthropogenic aerosols on meteorological elements and pollutants over Tianjin, China, was investigated using a fully coupled meteorology-chemistry model [Weather Research and Forecasting (WRF) model coupled with Chemistry (WRF-Chem)] for the entire year of 2021. The results showed that the ground solar radiation decreased from 208.84 W m−2 to 194.52 W m−2 due to DRE in Tianjin, and the percentage of the reduction was 6.86%. The reduction of ground solar radiation resulted in a 0.90% decrease in temperature, 1.13% decrease in boundary layer height, and 6.01% decrease in visibility, respectively, and a 0.80% increase in relative humidity. Changes in meteorological parameters changed the diffuse conditions of pollutants, leading to an increase of PM2.5. Higher concentration of pollutants leads to stronger DRE, and the percentages of changes caused by DRE on polluted days are higher than those on clean days. The DRE influence on pollutants can be summarized as a weather → aerosol → weather → air quality circulation mechanism. The DRE had more severe influence on meteorological elements and pollutants on foggy days. With the emission reduction of pollutants, the influence of the DRE has declined.
Immunogenomic Characteristics of Cell-Death-Associated Genes with Prognostic Implications in Bladder Cancer
Authors: Xu Wenhao , Tang Hai-Jia , Anwaier Aihetaimujiang , Liu Wangrui , Tian Xi , Su Jiaqi , Wei Shiyin , Qu Yuanyuan , Zhang Hailiang , Ye Dingwei 
Published: July 2022

Bladder cancer is one of the most common genitourinary malignant cancers worldwide. Cell death processes, including apoptosis, ferroptosis, and necrosis, provide novel clinical and immunological insights promoting the management of precision medicine. Therefore, this study aimed to evaluate the transcriptomic profile of signatures in cell death pathways with significant prognostic implications in patients with bladder cancer from multiple independent cohorts (n = 1999). First, genes involved in apoptosis (n = 19), ferroptosis (n = 31), and necrosis (n = 6) were analyzed to evaluate the prognostic implications in bladder cancer. Significant genes were included to establish the cell-death index (CDI) of 36 genes that distinguished patients according to high and low risks. Survival analysis using the Kaplan-Meier curves clustered patients based on overall survival (18.8 vs. 96.7 months; hazard model [HR] = 3.12, P&lt;00001). Cox proportional hazard model was significantly associated with a higher risk of mortality using 10 external independent cohorts in patients with CDIhigh (HR = 1.31, 95% CI: 1.04–1.62). To explore immune parameters associated with CDI, microenvironment cell-population-counter algorithms indicated increased intratumoral heterogeneity and macrophage/monocyte infiltration and CD8+ T cells in patients with CDIhigh group. Besides, the CDIhigh group showed an increased expression of the following immune checkpoints: CD276, PD-L1, CTLA-4, and T-cell exhaustion signatures. Cytokine expression analysis revealed the highest association of IL-9R, IL-17A, IL-17F, GDF7, and IFNW1 with the high-risk group. In addition, 42 patients with BCa receiving immunotherapies were enrolled from a real-world cohort, and expression patterns of three CDI hub genes (DRD5, SCL2A14, and IGF1) were detected using immunohistochemical staining. Patients with triple-negative staining of tumor tissues had significantly higher tumor-associated macrophage abundance, PD-L1 expression, predicted immunocompromised microenvironment, and prominently progressive progression (HR = 4.316, P = 0.0028). In conclusion, this study highlights the immunoevasive tumor microenvironment characterized by the higher tumor-associated macrophage infiltration with the presence of immune checkpoint and T-cell exhaustion genes in patients with BCa at CDIhigh risk who might suffer progression and be more suitable to benefit from immune checkpoint inhibitors or other immunotherapies.
Development of Live Attenuated Salmonella Typhimurium Vaccine Strain Using Radiation Mutation Enhancement Technology (R-MET)
Authors: Ji Hyun Jung , Jang A-Yeung , Song Joon Young , Ahn Ki Bum , Han Seung Hyun , Bang Seok Jin , Jung Ho Kyoung , Hur Jin , Seo Ho Seong 
Published: July 2022

Salmonella enterica is a leading cause of food-borne diseases in humans worldwide, resulting in severe morbidity and mortality. They are carried asymptomatically in the intestine or gallbladder of livestock, and are transmitted predominantly from animals to humans via the fecal-oral route. Thus, the best preventive strategy is to preemptively prevent transmission to humans by vaccinating livestock. Live attenuated vaccines have been mostly favored because they elicit both cellular and humoral immunity and provide long-term protective immunity. However, developing these vaccines is a laborious and time-consuming process. Therefore, most live attenuated vaccines have been mainly used for phenotypic screening using the auxotrophic replica plate method, and new types of vaccines have not been sufficiently explored. In this study, we used Radiation-Mutation Enhancement Technology (R-MET) to introduce a wide variety of mutations and attenuate the virulence of Salmonella spp. to develop live vaccine strains. The Salmonella Typhimurium, ST454 strain (ST WT) was irradiated with Cobalt60 gamma-irradiator at 1.5 kGy for 1 h to maximize the mutation rate, and attenuated daughter colonies were screened using in vitro macrophage replication capacity and in vivo mouse infection assays. Among 30 candidates, ATOMSal-L6, with 9,961-fold lower virulence than the parent strain (ST454) in the mouse LD50 model, was chosen. This vaccine candidate was mutated at 71 sites, and in particular, lost one bacteriophage. As a vaccine, ATOMSal-L6 induced a Salmonella-specific IgG response to provide effective protective immunity upon intramuscular vaccination of mice. Furthermore, when mice and sows were orally immunized with ATOMSal-L6, we found a strong protective immune response, including multifunctional cellular immunity. These results indicate that ATOMSal-L6 is the first live vaccine candidate to be developed using R-MET, to the best of our knowledge. R-MET can be used as a fast and effective live vaccine development technology that can be used to develop vaccine strains against emerging or serotype-shifting pathogens.
Cargo and Functional Profile of Saliva-Derived Exosomes Reveal Biomarkers Specific for Head and Neck Cancer
Authors: Hofmann Linda , Medyany Valentin , Ezić Jasmin , Lotfi Ramin , Niesler Beate , Röth Ralph , Engelhardt Daphne , Laban Simon , Schuler Patrick J. , Hoffmann Thomas K. , Brunner Cornelia , Jackson Edwin K. , Theodoraki Marie-Nicole 
Published: July 2022

BackgroundExosomes contribute to immunosuppression in head and neck squamous cell carcinoma (HNSCC), a tumor entity which lacks specific tumor biomarkers. Plasma-derived exosomes from HNSCC patients correlate with clinical parameters and have potential as liquid biopsy. Here, we investigate the cargo and functional profile of saliva-derived exosomes from HNSCC patients and their potential as non-invasive biomarkers for disease detection and immunomodulation.MethodsExosomes were isolated from saliva of HNSCC patients (n = 21) and healthy donors (HD, n = 12) by differential ultracentrifugation. Surface values of immune checkpoints and tumor associated antigens on saliva-derived exosomes were analyzed by bead-based flow cytometry using CD63 capture. Upon co-incubation with saliva-derived exosomes, activity and proliferation of T cells were assessed by flow cytometry (CD69 expression, CFSE assay). Adenosine levels were measured by mass spectrometry after incubation of saliva-derived exosomes with exogenous ATP. miRNA profiling of saliva-derived exosomes was performed using the nCounter® SPRINT system.ResultsSaliva-derived, CD63-captured exosomes from HNSCC patients carried high amounts of CD44v3, PDL1 and CD39. Compared to plasma, saliva was rich in tumor-derived, CD44v3+ exosomes and poor in hematopoietic cell-derived, CD45+ exosomes. CD8+ T cell activity was attenuated by saliva-derived exosomes from HNSCC patients, while proliferation of CD4+ T cells was not affected. Further, saliva-derived exosomes produced high levels of immunosuppressive adenosine. 62 HD- and 31 HNSCC-exclusive miRNAs were identified. Samples were grouped in “Healthy” and “Cancer” based on their saliva-derived exosomal miRNA profile, which was further found to be involved in RAS/MAPK, NF-κB complex, Smad2/3, and IFN-α signaling.ConclusionsSaliva-derived exosomes from HNSCC patients were enriched in tumor-derived exosomes whose cargo and functional profile reflected an immunosuppressive TME. Surface values of CD44v3, PDL1 and CD39 on CD63-captured exosomes, adenosine production and the miRNA cargo of saliva-derived exosomes emerged as discriminators of disease and emphasized their potential as liquid biomarkers specific for HNSCC.
Cations Do Not Alter the Membrane Structure of POPC—A Lipid With an Intermediate Area
Authors: Kurakin Sergei , Ivankov Oleksandr , Skoi Vadim , Kuklin Alexander , Uhríková Daniela , Kučerka Norbert 
Published: July 2022

Combining small-angle neutron scattering (SANS), small-angle X-ray scattering (SAXS), and densitometric measurements, we have studied the interactions of the divalent cations Ca2+ and Mg2+ with the lipid vesicles prepared of a mixed-chain palmitoyl-oleoyl-phosphatidylcholine (POPC) at 25°C. The structural parameters of the POPC bilayer, such as the bilayer thickness, lateral area, and volume per lipid, displayed no changes upon the ion addition at concentrations up to 30 mM and minor changes at &gt; 30 mM Ca2+ and Mg2+, while some decrease in the vesicle radius was observed over the entire concentration range studied. This examination allows us to validate the concept of lipid–ion interactions governed by the area per lipid suggested previously and to propose the mixed mode of those interactions that emerge in the POPC vesicles. We speculate that the average area per POPC lipid that corresponds to the cutoff length of lipid–ion interactions generates an equal but opposite impact on ion bridges and separate lipid–ion pairs. As a result of the dynamic equilibrium, the overall structural properties of bilayers are not affected. As the molecular mechanism proposed is affected by the structural properties of a particular lipid, it might help us to understand the fundamentals of processes occurring in complex multicomponent membrane systems.
Comparison of Recurrence Patterns and Salvage Treatments After Definitive Radiotherapy for cT1a and cT1bN0M0 Esophageal Cancer
Authors: Kawamoto Terufumi , Shikama Naoto , Mine Shinji , Sasai Keisuke 
Published: July 2022

BackgroundDefinitive radiotherapy (RT) for stage I esophageal cancer was reported to result in noninferior overall survival (OS) compared with surgery. However, only a few detailed reports of recurrence patterns and subsequent salvage treatments have been published. This study aimed to compare recurrence patterns and subsequent salvage treatments after definitive RT or chemoradiotherapy (CRT) between cT1a and cT1bN0M0 esophageal cancer (EC).MethodsPatients with cT1a or cT1bN0M0 esophageal squamous cell carcinoma who received definitive RT or CRT were included. Survival outcomes, recurrence patterns, and salvage treatments were evaluated.ResultsIn total, 40 patients with EC receiving RT or CRT were divided into two groups for evaluation: cT1a (20 patients) and cT1b (20 patients) groups. The 3-year OS rates were 83% and 65% (p = 0.06) and the 3-year progression-free survival rates were 68% and 44% (p = 0.15) in the cT1a and cT1b groups, respectively. Among those in the cT1a group, six had local recurrence and two had metachronous recurrence. Seven patients underwent salvage endoscopic submucosal dissection and one patient received argon plasma coagulation treatment. Among those in the cT1b group, six had local recurrence, one had regional recurrence, and one had both. Of these, one underwent salvage endoscopic submucosal dissection, one received photodynamic therapy, three underwent surgery, one received RT, and two received the best supportive care. Compared with the cT1b group, the cT1a group had a higher proportion of patients who underwent endoscopic treatments (p = 0.007). After the endoscopic treatments, no recurrences were observed in both groups.ConclusionsRegional recurrence and distant metastasis were not observed in the cT1a group. A higher proportion of patients in the cT1a group received salvage endoscopic treatments, and their OS tended to be favorable.
Nomogram Predicts Overall Survival in Patients With Stage IV Thyroid Cancer (TC): A Population-Based Analysis From the SEER Database
Authors: Yang Tianqing , Hu Tingting , Zhao Mingyi , He Qingnan 
Published: July 2022

BackgroundStage IV Thyroid cancer (TC) has a relatively poor prognosis and lacks a precise and efficient instrument to forecast prognosis. Our study aimed to construct a nomogram for predicting the prognosis of patients with stage IV TC based on data from the SEER programme.MethodsWe enrolled patients diagnosed with TC from 2004 to 2015 in the study. Furthermore, the median survival time (MST) for the patients equalled 25 months. The patients were split into two groups: the training group and validation group. We used descriptive statistics to calculate demographic and clinical variables, Student’s t test was used to describe continuous variables, and the chi-square test was used to describe classified variables. We used the concordance index (C-index) to evaluate discrimination ability and calibration plots to evaluate calibration ability. The improvement of the nomogram compared with the AJCC TNM system was evaluated by the net weight classification index (NRI), comprehensive discriminant rate improvement (IDI) and decision curve analysis (DCA).ResultsThere were 3501 patients contained within our cohort, and the median follow-up was 25 months [quartile range (IQR): 6-60] in the whole population, 25 months (IQR: 6-60) in the training cohort, and 25 months (IQR: 5-59) in the validation cohort. The C-index value of the training cohort equalled 0.86 (95% CI: 0.85-0.87), and the value of the validation cohort equalled 0.85 (95% CI: 0.84-0.86). The NRI values were as follows: training queue: 1.16 for three-year and 1.12 for five-year OS prediction; authentication group: 1.22 for three-year and 1.21 for five-year OS prediction. The IDI values were as follows: training cohort: 0.25 for three-year and 0.21 for five-year OS prediction; validation cohort: 0.27 for three-year and 0.21 for five-year OS prediction. The DCA diagram showed that the nomogram was superior in predicting the three-year and five-year trends.ConclusionsOur nomogram can be used to forecast the survival of patients with stage IV TC.