bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phosphorylation of Dynamin-Related Protein 1 (DRP1) Regulates Mitochondrial Dynamics and Skeletal Muscle Wasting in Cancer Cachexia
Authors: Mao Xiangyu , Gu Yihua , Sui Xiangyu , Shen Lei , Han Jun , Wang Haiyu , Xi Qiulei , Zhuang Qiulin , Meng Qingyang , Wu Guohao 
Published: August 2021

BackgroundCancer-associated cachexia (CAC) is a syndrome characterized by skeletal muscle atrophy, and the underlying mechanisms are still unclear. Recent research studies have shed light on a noteworthy link between mitochondrial dynamics and muscle physiology. In the present study, we investigate the role of dynamin-related protein 1 (DRP1), a pivotal factor of mitochondrial dynamics, in myotube atrophy during cancer-associated cachexia.MethodsSeventy-six surgical patients, including gastrointestinal tumor and benign disease, were enrolled in the study and divided to three groups: control, non-cachexia, and cancer-associated cachexia. Demographic data were collected. Their rectus abdominis samples were acquired intraoperatively. Muscle fiber size, markers of ubiquitin proteasome system (UPS), mitochondrial ultrastructure, and markers of mitochondrial function and dynamics were assayed. A cachexia model in vitro was established via coculturing a C2C12 myotube with media from C26 colon cancer cells. A specific DRP1 inhibitor, Mdivi-1, and a lentivirus of DRP1 knockdown/overexpression were used to regulate the expression of DRP1. Muscle diameter, mitochondrial morphology, mass, reactive oxygen species (ROS), membrane potential, and markers of UPS, mitochondrial function, and dynamics were determined.ResultsPatients of cachexia suffered from a conspicuous worsened nutrition status and muscle loss compared to patients of other groups. Severe mitochondrial swelling and enlarged area were observed, and partial alterations in mitochondrial function were found in muscle. Analysis of mitochondrial dynamics indicated an upregulation of phosphorylated DRP1 at the ser616 site. In vitro, cancer media resulted in the atrophy of myotube. This was accompanied with a prominent unbalance of mitochondrial dynamics, as well as enhanced mitochondrial ROS and decreased mitochondrial function and membrane potential. However, certain concentrations of Mdivi-1 and DRP1 knockdown rebalanced the mitochondrial dynamics, mitigating this negative phenotype caused by cachexia. Moreover, overexpression of DRP1 aggravated these phenomena.ConclusionIn clinical patients, cachexia induces abnormal mitochondrial changes and possible fission activation for the atrophied muscle. Our cachexia model in vitro further demonstrates that unbalanced mitochondrial dynamics contributes to this atrophy and mitochondrial impairment, and rebuilding the balance by regulating of DRP1 could ameliorate these alterations.
Development, Validation, and Application of a Novel Method for the Analysis of Vitamin E Acetate and Other Tocopherols in Aerosol Emissions of E-Cigarettes, or Vaping Products Associated With Lung Injury
Authors: Puetz Andrew , Morel Espinosa Maria , Watson Clifford , Blount Benjamin C. , Valentín-Blasini Liza 
Published: August 2021

E-cigarette, or vaping, product (EVP) use has increased dramatically in the United States over the last 4 years, particularly in youth and young adults. Little information is available on the chemical contents of these products. Typically, EVPs contain an active ingredient such as nicotine, CBD, or THC dissolved in a suitable solvent that facilitates aerosol generation. One EVP solvent, vitamin E acetate (VEA), has been measured in EVP liquids associated with lung injury. However, no validated analytical methods for measuring VEA in the aerosol from these devices was previously available. Therefore, we developed a high throughput isotope dilution LC-MS/MS method to simultaneously measure VEA and three other related tocopherols in aerosolized EVP samples. The assay was precise, with VEA repeatability ranging from 4.0 to 8.3% and intermediate precision ranging from 2.5 to 6.7%. Similar precision was obtained for the three other tocopherols measured. The LODs for the four analytes ranged from 8.85 × 10−6 to 2.28 × 10−5 μg analyte per mL of aerosol puff volume, and calibration curves were linear (R2 &gt; 0.99). This method was used to analyze aerosol emissions of 147 EVPs associated with EVALI case patients. We detected VEA in 46% of the case-associated EVPs with a range of 1.87 × 10−4–74.1 µg per mL of aerosol puff volume and mean of 25.1 µg per mL of aerosol puff volume. Macro-levels of VEA (&gt;0.1% w/w total aerosol particulate matter) were not detected in nicotine or cannabidiol (CBD) products; conversely 71% of the EVALI associated tetrahydrocannabinol (THC) products contained macro-levels of VEA. Trace levels of other tocopherol isoforms were detected at lower rates and concentrations (α-tocopherol: 41% detected, mean 0.095 µg analyte per mL of aerosol puff volume; γ-tocopherol: 5% detected, mean 0.0193 µg analyte per mL of aerosol puff volume; δ-tocopherol: not detected). Our results indicate that VEA can be efficiently transferred to aerosol by EVALI-associated EVPs vaped using a standardized protocol.
S-Propargyl-Cysteine Remodels the Gut Microbiota to Alleviate Rheumatoid Arthritis by Regulating Bile Acid Metabolism
Authors: Wang Zhou , Yu Yue , Liao Junyi , Hu Wei , Bian Xiqing , Wu Jianlin , Zhu Yi Zhun 
Published: August 2021

BackgroundRheumatoid arthritis (RA) is a long-term autoimmune disorder characterized by chronic inflammation that results in swollen and painful joints and even cartilage and bone damage. The gut microbiota, a novel anti-inflammatory target, is considered an important environmental factor in the development of RA. S-propargyl-cysteine (SPRC), an amino acid analogue, exerts anti-inflammatory, cardioprotective effects, and neuroprotective effects on various diseases. In recent studies, an SPRC treatment exerted anti-inflammatory effects on RA. Meanwhile, gut microbiome dysbiosis in individuals with RA has also been reported by many researchers. However, the relationship between SPRC and gut microbiota in individuals with RA remains unclear.MethodsThirty male Sprague-Dawley (SD) rats were randomly divided into three groups of 10 each, including the Control, Model, and SPRC groups. Adjuvant-induced arthritis (AIA) rats in SPRC group were treated with SPRC. Measurement of paw volume and serum tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) levels were applied to evaluate the inflammatory status. Fecal samples were collected on the 14th day and 28th day. Gut microbiota were analyzed using 16S ribosomal RNA (rRNA) gene amplicon sequencing. Untargeted metabolomics on plasma samples was applied to investigate the metabolic changes induced by the altered gut microbiota by using derivatization-UHPLC-Q-TOF/MS.FindingsUsing 16S rRNA amplicon sequencing, we found that SPRC significantly altered the gut microbiota structure in AIA rats. In particular, Bifidobacterium, a genus of BSH (Bile Salt Hydrolase)-producing microbes, was overrepresented in SPRC-treated AIA rats. Additionally, a subsequent metabolomics analysis indicated that bile acid metabolism was also altered by SPRC treatment. Interestingly, glycochenodeoxycholic acid (GCDCA) and glycocholic acid (GCA), which are formed with the participation of BSH-producing microbes in the intestine, were identified as crucial biomarkers responding to SPRC treatment with significantly lowered levels.InterpretationA mechanistic link between the gut microbiota and plasma metabolites was revealed in this study, which provides insights into the mechanism of SPRC treatment for RA from the perspective of the gut microbiota.
Experiences, Preferences, and Needs of Adolescents and Urban Youth in Contraceptive Use in Conakry, 2019, Guinea
Authors: Bangoura Charlotte , Dioubaté Nafissatou , Manet Hawa , Camara Bienvenu Salim , Kouyaté Mariama , Douno Moussa , Tetui Moses , El Ayadi Alison M. , Delamou Alexandre 
Published: August 2021

Introduction: The use of contraceptive methods is very low in Guinea, particularly among adolescents and young people. The purpose of this study is to analyze the experiences and expectations of adolescents and young people regarding the use of contraceptive methods in 2019 in Conakry, Guinea.Methods: We conducted a 6-month qualitative and descriptive study. Data were collected through individual in-depth interviews and focus group discussions with adolescents and young people, health providers and health policy makers. Two approaches of deductive and inductive analysis were used to synthesize the main insights from the data.Findings: Twenty-six participants were included in this study. Adolescents and young people have personal, family and community experiences that positively or negatively influence their contraceptive needs and preferences. Positive experiences include the relative cost of injectable forms, perceived absence of side effects of implants, proven efficacy and duration of action of the modern method used (implants and injectable form). Negative experiences included cost of implants remain high (15 Euros), perceived side effects including weight gain, pill compliance, method indiscretion, and low sensation of sexual pleasure for the condom. The preferences of the young participants were dominated by Implants and injectable forms that better meet their contraceptive needs. In terms of needs, the expectations expressed revolved around needs related to the health system, including sex education, reduction in the cost of some contraceptives (implants), availability of contraceptive methods, and equity in the provision of family planning services to adolescents and young people.Conclusion: Exploring the contraceptive experiences, needs and preferences of adolescents and young people reveals decision-making dilemmas. Adolescents and young people expressed their experiences in terms of the cost of preferred contraceptives (implants), side effects, proven efficacy, and duration of action. However, their decisions are still influenced by availability, equity in service delivery, and the involvement of parents and religious leaders in sex education. Decision-makers should then place particular emphasis on improving health service delivery, adolescent sexual and reproductive health, availability of preferred contraceptive methods at affordable cost, and a program on sexuality education with the involvement of parents and religious leaders and the promotion of condom use.
One Gene, Many Facets: Multiple Immune Pathway Dysregulation in SOCS1 Haploinsufficiency
Authors: Körholz Julia , Gabrielyan Anastasia , Sowerby John M. , Boschann Felix , Chen Lan-Sun , Paul Diana , Brandt David , Kleymann Janina , Kolditz Martin , Toepfner Nicole , Knöfler Ralf , Jacobsen Eva-Maria , Wolf Christine , Conrad Karsten , Röber Nadja , Lee-Kirsch Min Ae , Smith Kenneth G. C. , Mundlos Stefan , Berner Reinhard , Dalpke Alexander H. , Schuetz Catharina , Rae William 
Published: August 2021

BackgroundInborn errors of immunity (IEI) present with a large phenotypic spectrum of disease, which can pose diagnostic and therapeutic challenges. Suppressor of cytokine signaling 1 (SOCS1) is a key negative regulator of cytokine signaling, and has recently been associated with a novel IEI. Of patients described to date, it is apparent that SOCS1 haploinsufficiency has a pleiotropic effect in humans.ObjectiveWe sought to investigate whether dysregulation of immune pathways, in addition to STAT1, play a role in the broad clinical manifestations of SOCS1 haploinsufficiency.MethodsWe assessed impacts of reduced SOCS1 expression across multiple immune cell pathways utilizing patient cells and CRISPR/Cas9 edited primary human T cells.ResultsSOCS1 haploinsufficiency phenotypes straddled across the International Union of Immunological Societies classifications of IEI. We found that reduced SOCS1 expression led to dysregulation of multiple intracellular pathways in immune cells. STAT1 phosphorylation is enhanced, comparably with STAT1 gain-of-function mutations, and STAT3 phosphorylation is similarly reduced with concurrent reduction of Th17 cells. Furthermore, reduced SOCS1 E3 ligase function was associated with increased FAK1 in immune cells, and increased AKT and p70 ribosomal protein S6 kinase phosphorylation. We also found Toll-like receptor responses are increased in SOCS1 haploinsufficiency patients.ConclusionsSOCS1 haploinsufficiency is a pleiotropic monogenic IEI. Dysregulation of multiple immune cell pathways may explain the variable clinical phenotype associated with this new condition. Knowledge of these additional dysregulated immune pathways is important when considering the optimum management for SOCS1 haploinsufficient patients.
Efficacy of Humanized Anti-BCMA CAR T Cell Therapy in Relapsed/Refractory Multiple Myeloma Patients With and Without Extramedullary Disease
Authors: Deng Haobin , Liu Meijing , Yuan Ting , Zhang Huan , Cui Rui , Li Jingyi , Yuan Jijun , Wang Xiaofang , Wang Yafei , Deng Qi 
Published: August 2021

In recent years, many new treatments for relapsed/refractory (R/R) multiple myeloma (MM) have improved patient prognosis, but the prognosis of patients with extramedullary MM is still particularly poor. Therefore, more efficacious therapies and novel strategies are urgently needed for these patients. The aim of this study was to observe and compare the efficacy and safety of humanized anti-B cell maturation antigen (anti-BCMA) chimeric antigen receptor (CAR) T cell therapy in R/R MM patients with and without extramedullary disease. Seven R/R MM patients with extramedullary disease and 13 without extramedullary disease received humanized anti-BCMA CAR T cell therapy. The overall response rate was not different between patients with and without extramedullary disease. There was no difference in the progression-free survival (PFS) or overall survival (OS) rates between the two groups at 180 days, but the PFS and OS rates in patients with extramedullary disease were lower at 360 days than those in patients without extramedullary disease. Although some patients with extramedullary disease experienced further disease progression, their M protein level did not increase. We did not see this change trend of M protein in patients without extramedullary disease. However, this was not observed in patients without extramedullary disease. Among patients who responded to CAR T cell therapy, the grades of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxic syndrome (ICANS) were much higher among patients with extramedullary disease. In summary, R/R MM patients with extramedullary disease could benefit from humanized anti-BCMA CAR T cell therapy in the short term, although the CRS and ICANS grades were much higher in patients with extramedullary disease. Therefore, anti-BCMA CAR T cell therapy allows for a remission time for R/R MM patients with extramedullary disease, which could be maintained by bridging hematopoietic stem cell transplantation, radiotherapy, and other therapies.Clinical Trial Registrationhttp://www.chictr.org.cn/index.aspx, identifiers ChiCTR1800017051 and ChiCTR2000033925.
Clinical Evaluation for Sublingual Immunotherapy With Dermatophagoides farinae in Polysensitized Allergic Asthma Patients
Authors: Zhang Ai-zhi , Liang Mei-e , Chen Xiao-xue , Wang Yan-fen , Ma Ke , Lin Zhi , Xue Kuan-kuan , Cao Li-ru , Yang Rong , Zhang Huan-ping 
Published: August 2021

Background: Many studies have demonstrated the efficacy of single-allergen sublingual immunotherapy (SLIT) in polysensitized patients with allergic rhinitis (AR), but less is reported in polysensitized patients with allergic asthma (AS).Method: Data of 133 adult patients with house dust mite (HDM)-induced AS who had been treated for 3 years were collected. These patients were divided into the control group (treated with low to moderate dose of inhaled glucocorticoids and long-acting β2 agonists, n = 37) and the SLIT group (further treated with Dermatophagoides farinae drops, n = 96). The SLIT group contained three subgroups: the single-allergen group (only sensitized to HDM, n = 35), the 1- to 2-allergen group (HDM combined with one to two other allergens, n = 32), and the 3-or-more-allergen group (HDM combined with three or more other allergens, n = 29). The total asthma symptom score (TASS), total asthma medicine score (TAMS), and asthma control test (ACT) were assessed before treatment and at yearly visits. Forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) was assessed before treatment and at the end of SLIT.Results: TASS and ACT scores in the control group were significantly higher than that in the single-allergen group and the 1- to 2-allergen group after 1, 2, and 3 years of SLIT and significantly higher than that in the 3-or-more-allergen group after 3-year SLIT (all p &lt; 0.05). TAMS of the control group was significantly higher than that of the other three groups after 0.5, 1, 2, and 3 years of SLIT (all p &lt; 0.05). FEV1/FVC in the control group was significantly higher than baseline after 3 years of immunotherapy (p &lt; 0.05).Conclusion: Patients sensitized to HDM with/without other allergens showed similar efficacy after 3 years of SLIT. However, the initial response of patients with three or more allergens was slower during immunotherapy process.
The Clinical Application of Robot-Assisted Ventriculoperitoneal Shunting in the Treatment of Hydrocephalus
Authors: Liu De-feng , Liu Huan-guang , Zhang Kai , Meng Fan-gang , Yang An-chao , Zhang Jian-guo 
Published: August 2021

BackgroundThis work aims to assess the effectiveness and safety of robotic assistance in ventriculoperitoneal shunting and to compare the results with data from traditional surgery.MethodsWe retrospectively analyzed 60 patients who had undergone ventriculoperitoneal shunting, of which shunts were implanted using a robot in 20 patients and using traditional surgical methods in the other 40 patients. Data related to surgery were compared between the two groups, and the accuracy of the drainage tube in the robot-assisted group was assessed.ResultsIn the robot-assisted surgery group, the operation duration was 29.75 ± 6.38 min, intraoperative blood loss was 10.0 ± 3.98 ml, the success rate of a single puncture was 100%, and the bone hole diameter was 4.0 ± 0.3 mm. On the other hand, the operation duration was 48.63 ± 6.60 min, intraoperative blood loss was 22.25 ± 4.52 ml, the success rate of a single puncture was 77.5%, and the bone hole diameter was 11.0 ± 0.2 mm in the traditional surgery group. The above are statistically different between the two groups (P &lt; 0.05). Only one case of surgery-related complications occurred in the robot-assisted group, while 13 cases occurred in the traditional surgery group. There was no significant difference in the hospitalization time. In the robot-assisted surgery group, the average radial error was 2.4 ± 1.5 mm and the average axial error was 1.9 ± 2.1 mm.ConclusionIn summary, robot-assisted implantation is accurate, simple to operate, and practical; the duration of surgery is short; trauma to the patient is reduced; and fewer postoperative complications related to surgery are reported.
Development and Usability Study of an Open-Access Interviewer-Administered Automated 24-h Dietary Recall Tool in Argentina: MAR24
Authors: Contreras-Guillén Ismael A. , Leeson Sara , Gili Rocio V. , Carlino Belén , Xutuc Daniel , Martins Marcia Cristina Teixeira , Zapata María E. , Segovia-Siapco Gina , Sabaté Joan , Pacheco Fabio J. , Pacheco Sandaly O. S. 
Published: August 2021

Background: Latin American countries show a fast-growing rate of non-communicable diseases (NCDs) and diet is a critical risk factor that must be properly assessed. Automated dietary assessment tools to collect 24-h dietary recalls (24HR) are lacking in Argentina.Objective: This study aimed to develop an open-access automated tool (MAR24) for collecting 24HR using a multiple pass method and a database containing foods and recipes commonly consumed in Argentina.Methods: MAR24 was developed based on data from 1,285 24HR provided by male and female participants aged 18 to 68 years from the six Argentinian geographical regions. The main structure and interface of the tool were designed using Visual Basic for Applications programming language in Excel Microsoft Office 365, integrating the five steps of the United States Department of Agriculture (USDA) Automated Multiple-Pass Method (AMPM) for the application of 24HR in Spanish. The tool underwent alpha testing and expert assessment to address structural and usability issues. Critical feedback and face validation from researchers and experienced dietitians, and repeated testing to collect 24HR were used to adjust and improve the tool.Results: A total of 968 food items and 100 standard Argentinian recipes were added to its database. MAR24 allows the estimation of the nutrient profile of dietary intake. The analytic food composition includes energy and 50 nutrients including water, macronutrients, total dietary fiber, total sugar, 10 minerals, 19 vitamins, eight fatty acids, cholesterol, ethyl alcohol, caffeine, and theobromine. MAR24 includes a user manual and technical manual to guide users to apply changes (e.g., add foods or recipes, or change food designation according to local terms) to fit different research and clinical applications.Conclusions: MAR24 is the first tool that uses the AMPM methodology for 24HR applications in Argentina. The tool may be used in clinical practice and clinical trials for monitoring purposes, and in validation of food frequency questionnaires (FFQ) for nutritional epidemiology studies addressing dietary-associated risk factors for NCDs.
Pyrotinib Plus Vinorelbine Versus Lapatinib Plus Capecitabine in Patients With Previously Treated HER2-Positive Metastatic Breast Cancer: A Multicenter, Retrospective Study
Authors: Xie Yizhao , Li Yi , Ting Luo , Sang Die , Yuan Peng , Li Wei , Li Huihui , Ge Rui , Wang Biyun 
Published: August 2021

BackgroundPyrotinib is a newly-developed irreversible pan-ErbB (erythroblastic leukemia viral oncogene homolog) receptor oral tyrosine kinase inhibitor (TKI) with promising efficacy in the human epidermal growth factor receptor-2 (HER2) positive breast cancer. The phase III PHOEBE study proved that pyrotinib plus capecitabine exceeded lapatinib plus capecitabine (LX) in PFS (p &lt; 0.001). Oral vinorelbine is commonly used in combination with anti-HER2 treatment. However, no evidence was reported in terms of the real-world pattern, safety, and efficacy of pyrotinib plus vinorelbine (NP) compared with LX.MethodsMedical records were retrospectively evaluated for all HER2-positive metastatic breast cancer (MBC) patients who experienced progression on prior trastuzumab-containing regimens (advanced setting) and taxane (any setting) and received NP or LX therapy from 2015 to 2021 in five institutions.ResultsA total of 224 patients were enrolled and evaluated, of which 132 (58.9%) patients received LX and 92 (41.1%) patients received NP. The median progression-free survival (mPFS) of NP group was significantly longer than that in LX group (8.3 vs 5.0 months, HR = 0.47 95% CI 0.34–0.65, p &lt; 0.001). The advantage of NP over LX was seen both in patients with trastuzumab resistance (p &lt; 0.001) and refractoriness (p = 0.004). The NP group had more diarrhea cases (23.9%) compared to the LX group (8.3%). Discontinuation rates in the two groups were similar.ConclusionsThis trial revealed the clinical practice of NP and LX treatment among HER2+ MBC patients pretreated with trastuzumab in China. More patients received LX than NP in real-world while the efficacy of NP exceeded LX in terms of PFS regardless of resistant status of trastuzumab. Although the NP group had more diarrhea cases, toxicities in both groups were acceptable.