bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gut microbiota is correlated with gastrointestinal adverse events of metformin in patients with type 2 diabetes
Authors: Huang Yuxin , Lou Xudan , Jiang Cuiping , Ji Xueying , Tao Xiaoming , Sun Jiao , Bao Zhijun 
Published: November 2022

AimGastrointestinal discomfort is the most common adverse event in metformin treatment for type 2 diabetes. The mechanism of action of metformin is associated with gut microbiota. However, the gut microbial community structure related to metformin-induced gastrointestinal adverse events remains unclear. This study aimed to investigate it.Methods50 patients with newly diagnosed diabetes were treated with metformin 1500mg/d for 12 weeks. The patients were divided into two groups according to whether gastrointestinal adverse events occurred (group B) or did not occur (group A) after treatment. The fecal bacterial communities and short-chain fatty acids (SCFAs) were sequenced and compared. 70 diabetes mice were randomly divided into 8 groups and treated with metformin (Met), clindamycin (Clin) and/or SCFA, which were the Met+/Clin+, Met+/Clin-, Met-/Clin+, Met-/Clin-, Met+/SCFA+, Met+/SCFA-, Met-/SCFA+ and Met-/SCFA- group. After 4 weeks of metformin treatment, blood glucose, food intake, fecal SCFAs, gut microbiota and gut hormones were measured.ResultsMetformin increased the abundance of Phascolarctobacterium, Intestinimonas and Clostridium III. Functional prediction analysis showed that the propanoate metabolism pathway was significantly up-regulated. The concentrations of acetic acid and propanoic acid in feces were significantly increased. The abundance of Clostridium sensu stricto, Streptococcus and Akkermansia induced by metformin in group B was higher than that in group A. The propanoate metabolism pathway and propanoic acid in feces were significantly up-regulated in group B. In the animal experiments, the food intake decreased and glucose control increased in metformin groups compared with those in the control groups. The total GLP-1 level in the Met+/Clin- group was significantly higher than that in the Met-/Clin- group, while there was no statistical difference between the Met-/Clin- and Met+/Clin+ group. The total GLP-1 level in the Met-/SCFA+ group was significantly higher than that in the Met-/SCFA-group, while the levels of total GLP-1 and active GLP-1 in the Met+/SCFA- group and the Met+/SCFA+ group were significantly higher than those in the Met-/SCFA-group.ConclusionsOur data suggest that metformin promotes the secretion of intestinal hormones such as GLP-1 by increasing the abundance of SCFA-producing bacteria, which not only plays an anti-diabetic role, but also may causes gastrointestinal adverse events.
“Short agonist stop” protocol, an ovarian stimulation for poor responders in in vitro fertilization (IVF): A pilot study
Authors: Mauries Charlotte , Ranisavljevic Noemie , Mollevi Caroline , Brunet Cecile , Hamamah Samir , Brouillet Sophie , Anahory Tal 
Published: November 2022

IntroductionPoor responder patients remain a challenge in assisted reproductive technologies. The “short agonist stop” (SAS) stimulation protocol uses a double stimulation (flare up effect with the gonadotropin-releasing hormone (GnRH) agonist (GnRH-a) then gonadotropins) associated with a less strenuous blockage (discontinuation of GnRH-a) to favor follicular recruitment in order to obtain a better ovarian response. This study aims to compare the number of oocytes obtained after a SAS stimulation protocol with those obtained after the previous stimulation protocol, in the same women, with poor ovarian response (POR) diagnosed according to the POSEIDON criteria.DesignThis therapeutic observational retrospective cohort from 2018 to 2022, with a case-control evaluation compared with the same patients’ previous performance, included women with POR undergoing IVF with SAS stimulation protocol. The primary outcome was the number of total oocytes recovered and secondary outcomes were the numbers of mature oocytes, total embryos observed at day 2 and usable cleaved embryos and blastocysts (day 5/6).Results63 patients with SAS and previous cycles were included. In the SAS group, the mean number of oocytes was significantly higher: 7.3 vs 5.7, p=0.018 in comparison with the previous attempt. So was the number of mature oocytes (5.8 vs 4.1, p=0.032) and the total mean number of embryos obtained at day 2 (4.1 versus 2.7, p=0.016). The SAS stimulation generated 84 usable embryos: 57 cleaved embryos and 27 blastocysts. The mean number of usable embryos was similar in both groups (1.64 vs 1.31, respectively, p=0.178). In total, out of 63 patients, after the SAS protocol, and subsequent embryo transfers (fresh and frozen, n=54), 9 patients had ongoing pregnancies and no miscarriage occurred. The cumulative ongoing pregnancy rate (cOPR) after the SAS protocol was 14.3% (9/63) per oocyte pick-up and 16.7% (9/54) per transfer.ConclusionSAS stimulation is a short and original protocol strengthening the therapeutic arsenal of poor responders, that may offer promising results for those patients with low prognosis and previous failed IVF. Results must be confirmed with a randomized controlled trial.
miRNA–mRNA–protein dysregulated network in COPD in women
Authors: Li Chuan Xing , Gao Jing , Sköld C. Magnus , Wheelock Åsa M. 
Published: November 2022

Rationale: Chronic obstructive pulmonary disease (COPD) is a complex disease caused by a multitude of underlying mechanisms, and molecular mechanistic modeling of COPD, especially at a multi-molecular level, is needed to facilitate the development of molecular diagnostic and prognostic tools and efficacious treatments.Objectives: To investigate the miRNA–mRNA–protein dysregulated network to facilitate prediction of biomarkers and disease subnetwork in COPD in women.Measurements and Results: Three omics data blocks (mRNA, miRNA, and protein) collected from BAL cells from female current-smoker COPD patients, smokers with normal lung function, and healthy never-smokers were integrated with miRNA–mRNA–protein regulatory networks to construct a COPD-specific dysregulated network. Furthermore, downstream network topology, literature annotation, and functional enrichment analysis identified both known and novel disease-related biomarkers and pathways. Both abnormal regulations in miRNA-induced mRNA transcription and protein translation repression play roles in COPD. Finally, the let-7-AIFM1-FKBP1A pathway is highlighted in COPD pathology.Conclusion: For the first time, a comprehensive miRNA–mRNA–protein dysregulated network of primary immune cells from the lung related to COPD in females was constructed to elucidate specific biomarkers and disease pathways. The multi-omics network provides a new molecular insight from a multi-molecular aspect and highlights dysregulated interactions. The highlighted let-7-AIFM1-FKBP1A pathway also indicates new hypotheses of COPD pathology.
Identification of four novel variants in the CDH23 gene from four affected families with hearing loss
Authors: Kang Baoling , Lu Xinshu , Xiong Jianjun , Li Yuan , Zhu Jinwen , Cai Tao 
Published: November 2022

Background: Hearing loss (HL) is the most common form of sensory disorder in humans. Molecular diagnosis of HL is important for genetic counseling for the affected individuals and their families.Methods: To identify potential genetic causes, we performed whole-exome sequencing and related biomedical informatics for 351 non-syndromic HL patients and their family members.Results: In the present study, we report the identification of four compound heterozygous variants in the CDH23 gene from four affected families, including four novel variants (c.995C&gt;A, p.T332K; c.2159G&gt;A, p.R720Q; c.5534A&gt;G, p.N1845S, and c.7055-1G&gt;C) and two frequently reported variants (c.719C&gt;T, p.P240L and c.4762C&gt;T, p.R1588W).Conclusion: Our findings significantly expanded the mutation spectrum of CDH23-associated autosomal recessive hearing loss.
Comprehensive analysis of cuproptosis-related lncRNAs to predict prognosis and immune infiltration characteristics in colorectal cancer
Authors: Zhu Zhonglin , Zhao Qiuyan , Li Shanbao , Weng Junyong , Guo Tianan , Zhu Congcong , Xu Ye 
Published: November 2022

Background: Cuproptosis is a novel form of cell death discovered in recent. A great quantity of researches has confirmed the close relationships and crucial roles between long non-coding RNAs (lncRNAs) with the progression of colorectal cancer (CRC). However, the relationship between cuproptosis and lncRNAs remains unclear in CRC.Methods: 1,111 co-expressed lncRNAs with 16 cuproptosis regulators were retrieved from CRC samples of The Cancer Genome Atlas (TCGA) database. Through univariate Cox and least absolute shrinkage and selection operator regression analysis, a prognosis model was constructed with 15 lncRNAs. The Kaplan-Meier, receiver operating characteristic curve, C-index and principal component analysis identified the prognostic power. Furthermore, a cuproptosis-related cluster was generated based on the 15 lncRNAs by unsupervised methods. The correlations between the cuproptosis-related signatures with immune cell infiltration and anti-tumor therapy were explored by multiple algorithms.Results: A risk score and nomogram with great prediction ability were constructed for CRC prognosis evaluation. The immune activate pathways, immune infiltration cells, immune functions, immune score and immune activation genes were remarkably enriched in the high risk group. The cuproptosis-related cluster was generated, of which the cluster 2 showed longer overall survival. The immune cell infiltration analysis indicated the similar results of cluster 2 with the high risk group, implying a significant marker for “hot tumor.” The cluster 2 also presented high expression of immune checkpoint molecules, MSI-H status and higher susceptibility to multiple immunotherapy drugs.Conclusion: We appraised a novel cuproptosis-related prognosis model and molecular signature associated with prognosis, immune infiltration and immunotherapy. The identification of cuproptosis-related lncRNAs improved our understanding of immune infiltration and provided a significant marker for prognosis and immunotherapy in CRC.
Prospective longitudinal analysis of antibody response after standard and booster doses of SARS-COV2 vaccination in patients with early breast cancer
Authors: Kim Jinyong , Jeong Jiyun , Lee Chan Mi , Lee Dae-Won , Kang Chang Kyung , Choe Pyeong Gyun , Kim Nam Joong , Oh Myoung-don , Lee Chang-Han , Park Wan Beom , Lee Kyung-Hun , Im Seock-Ah 
Published: November 2022

IntroductionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants brought waves of pandemics with breakthrough infections in vaccinated individuals. We analyzed the antibody responses after primary and booster vaccination in healthy controls (HC) and patients with early breast cancer (BC).MethodsIn this prospective longitudinal cohort study, the binding activity of serum antibody level against spike proteins and antigens of SARS-CoV-2 variants was measured within 21 days after each vaccination in the BC group and HC group.ResultsAll participants, 40 in the BC and 20 in the HC group, had increased antibody response after vaccination. BC group, however, had weaker humoral responses than the HC group (IgG: 1.5, 2.3, 2.5-folds in BC vs. 1.9, 3.6, 4.0-folds in HC after each dose; IgA: 2.1, 3.0, 3.6-folds in BC vs. 4.2, 10.4, 5.2-folds in HC after each dose, respectively). Those under concurrent cytotoxic chemotherapy had weaker antibody response than the non-cytotoxic treatment group and HC. Adjunct use of steroids and age were not significant risk factors. The levels of binding antibody against the Delta and the Omicron (BA1) variants were lower than the wild-type, especially in BC.ConclusionIn the waves of new sub-variants, our study suggests that an additional dose of vaccinations should be recommended according to the anti-cancer treatment modality in patients with BC who had received booster vaccination.
Age related immune modulation of experimental autoimmune encephalomyelitis in PINK1 knockout mice
Authors: Cossu Davide , Yokoyama Kazumasa , Sato Shigeto , Noda Sachiko , Sakanishi Tamami , Sechi Leonardo Antonio , Hattori Nobutaka 
Published: November 2022

ObjectiveRecent research has shown that Parkin, an E3 ubiquitin ligase, modulates peripheral immune cells-mediated immunity during experimental autoimmune encephalomyelitis (EAE). Because the PTEN-induced putative kinase 1 (PINK1) protein acts upstream of Parkin in a common mitochondrial quality control pathway, we hypothesized that the systemic deletion of PINK1 could also modify the clinical course of EAE, altering the peripheral and central nervous systems’ immune responses.MethodsEAE was induced in female PINK1-/- mice of different age groups by immunization with myelin oligodendrocyte glycoprotein peptide.ResultsCompared to young wild-type controls, PINK1-/- mice showed earlier disease onset, albeit with a slightly less severe disease, while adult PINK1-/- mice displayed early onset and more severe acute symptoms than controls, showing persistent disease during the recovery phase. In adult mice, EAE severity was associated with significant increases in frequency of dendritic cells (CD11C+, IAIE+), lymphocytes (CD8+), neutrophils (Ly6G+, CD11b+), and a dysregulated cytokine profile in spleen. Furthermore, a massive macrophage (CD68+) infiltration and microglia (TMEM119+) and astrocyte (GFAP+) activation were detected in the spinal cord of adult PINK1-/- mice.ConclusionsPINK1 plays an age-related role in modulating the peripheral inflammatory response during EAE, potentially contributing to the pathogenesis of neuroinflammatory and other associated conditions.
Pathologic responses and surgical outcomes after neoadjuvant immunochemotherapy versus neoadjuvant chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma
Authors: Xu Lei , Wei Xiu-feng , Li Can-jun , Yang Zhao-yang , Yu Yong-kui , Li Hao-miao , Xie Hou-nai , Yang Ya-fan , Jing Wei-wei , Wang Zhen , Kang Xiao-zheng , Zhang Rui-xiang , Qin Jian-jun , Xue Li-yan , Bi Nan , Chen Xian-kai , Li Yin 
Published: November 2022

BackgroundCurrently, the role of immunotherapy in neoadjuvant setting for patients with locally advanced esophageal squamous cell carcinoma (ESCC) is gradually attracting attention. Few studies compared the efficacy of neoadjuvant immunochemotherapy (NICT) and neoadjuvant chemoradiotherapy (NCRT). Our study aimed to compare treatment response and postoperative complications after NICT followed by surgery with that after conventional NCRT in patients with locally advanced ESCC.MethodsOf 468 patients with locally advanced ESCC, 154 received conventional NCRT, whereas 314 received NICT. Treatment response, postoperative complications and mortality between two groups were compared. Pathological response of primary tumor was evaluated using the Mandard tumor regression grade (TRG) scoring system. Pathological complete response (pCR) of metastatic lymph nodes (LNs) was defined as no viable tumor cell within all resected metastatic LNs. According to regression directionality, tumor regression pattern was summarized into four categories: type I, regression toward the lumen; type II, regression toward the invasive front; type III, concentric regression; and type IV, scattered regression. Inverse probability propensity score weighting was performed to minimize the influence of confounding factors.ResultsAfter adjusting for baseline characteristics, the R0 resection rates (90.9% vs. 89.0%, P=0.302) and pCR (ypT0N0) rates (29.8% vs. 34.0%, P=0.167) were comparable between two groups. Patients receiving NCRT showed lower TRG score (P&lt;0.001) and higher major pathological response (MPR) rate (64.7% vs. 53.6%, P=0.001) compared to those receiving NICT. However, NICT brought a higher pCR rate of metastatic LNs than conventional NCRT (53.9% vs. 37.1%, P&lt;0.001). The rates of type I/II/III/IV regression patterns were 44.6%, 6.8%, 11.4% and 37.1% in the NICT group, 16.9%, 8.2%, 18.3% and 56.6% in the NCRT group, indicating a significant difference (P&lt;0.001). Moreover, there were no significant differences in the incidence of total postoperative complications (35.8% vs. 39.9%, P=0.189) and 30-d mortality (0.0% vs. 1.1%, P=0.062).ConclusionFor patients with locally advanced ESCC, NICT showed a R0 resection rate and pCR (ypT0N0) rate comparable to conventional NCRT, without increased incidence of postoperative complications and mortality. Notablely, NICT followed by surgery might bring a promising treatment response of metastatic LNs.
Clostridium butyricum potentially improves inflammation and immunity through alteration of the microbiota and metabolism of gastric cancer patients after gastrectomy
Authors: Cao Wenjie , Zheng Cihua , Xu Xuan , Jin Rui , Huang Feng , Shi Meng , He Zhipeng , Luo Yufeng , Liu Lulin , Liu Zhaoxia , Wei Jing , Deng Xiaorong , Chen Tingtao 
Published: November 2022

BackgroundGastrectomy is the most effective treatment to improve the clinical survival rate of patients with gastric cancer. However, the pathophysiological changes caused by gastrectomy have seriously affected the postoperative recovery.MethodsIn the present trial, Ataining (containing C. butyricum, CGMCC0313.1) was applied in patients after gastrectomy to investigate the effect of C. butyricum on the early postoperative recovery by monitoring the inflammatory immune response with blood indicators, detecting the gut microbiota with high-throughput sequencing, and analyzing the short-chain fatty acids (SCFAs) with targeted metabolomics. This study is registered with the number ChiCTR2000040915.ResultsOur outcomes revealed that C. butyricum had significantly reduced the number of Leucocyte (P &lt; 0.001), the percentage of Neutrophil (P &lt; 0.001), the expression of IL-1β (P &lt; 0.01), IL-6 (P &lt; 0.05), and TNF-α (P &lt; 0.01), while markedly enhanced the immunity indexes (immunoglobulin and lymphocyte) (P &lt; 0.05) and nutrition indexes (albumin and total protein) (P &lt; 0.05). In addition, the use of the C. butyricum greatly enriched the relative abundance of beneficial bacteria Bacteroides, Faecalibacterium and Gemmiger, while the abundance of pathogenic Streptococcus, Desulfovibrio and Actinomyces were markedly decreased at genus level. We also observed significant up-regulation of SCFAs, including acetic acid, propionic acid, butyric acid and isobutyric acid, after C. butyricum administration in patients receiving gastrectomy.ConclusionTherefore, evidence supported that oral administration of C. butyricum after gastrectomy can reduce early postoperative inflammation, enhance immune ability, restore intestinal microbiota eubiosis, increase intestinal SCFAs, reduce the occurrence of postoperative complications, and ultimately promote the early recovery of the patient.Clinical trial registrationhttp://www.chictr.org.cn/, identifier (ChiCTR2000040915).
Biogenic calcium carbonate derived from waste shells for advanced material applications: A review
Authors: Azarian Mohammad Hossein , Sutapun Wimonlak 
Published: November 2022

Biogenic calcium carbonate derived from waste shells has received significant attention in the last 2 decades as a replacement for limestone due to its contribution to reducing environmental impact by turning wastes into value-added biomaterial and moving global society toward net-zero waste. Recently, several review papers have been published regarding applying biogenic derived calcium carbonate in engineering, biomedical, electrochemical, and environmental technologies. This review stands apart from other reviews on this topic in terms of focusing and reviewing the published papers used and reported indirect methods only to obtain calcium carbonate from biogenic waste shells and not by direct methods. The direct or untreated methods include simple grinding, ball milling, or mortar and pestle techniques. In contrast, the indirect methods covered in this review paper consist of precipitation and different chemical treatment techniques. Therefore, this review paper aims to comprehensively summarize the usage of calcium carbonate derived from eggshells and seashells by indirect methods and glance at its recent development for advanced material applications including water treatment, bio-filler, and reinforcement in polymer composites, energy application, pharmaceutical, biomedical, and drug delivery applications.
Hospital-acquired bloodstream infections in patients deceased with COVID-19 in Italy (2020–2021)
Authors: Monaco Monica , Floridia Marco , Giuliano Marina , Palmieri Luigi , Lo Noce Cinzia , Pantosti Annalisa , Palamara Anna Teresa , Brusaferro Silvio , Onder Graziano ,   The Italian National Institute of Health COVID-19 Mortality Group
Published: November 2022

IntroductionIn hospitalized patients with COVID-19, bloodstream infections (BSI) are associated with high mortality and high antibiotic resistance rates. The aim of this study was to describe BSI etiology, antimicrobial resistance profile and risk factors in a sample of patients deceased with COVID-19 from the Italian National COVID-19 surveillance.MethodsHospital charts of patients who developed BSI during hospitalization were reviewed to describe the causative microorganisms and their antimicrobial susceptibility profiles. Risk factors were analyzed in univariate and multivariate analyses.ResultsThe study included 73 patients (71.2% male, median age 70): 40 of them (54.8%) received antibiotics and 30 (41.1%) systemic steroids within 48 h after admission; 53 (72.6%) were admitted to intensive care unit. Early steroid use was associated with a significantly shorter interval between admission and BSI occurrence. Among 107 isolated microorganisms, the most frequent were Enterococcus spp., Candida spp., Acinetobacter baumannii, and Klebsiella pneumoniae. Median time from admission to BSI was shorter for Staphylococcus aureus compared to all other bacteria (8 vs. 24 days, p = 0.003), and longer for Enterococcus spp., compared to all other bacteria (26 vs. 18 days, p = 0.009). Susceptibility tests showed a high rate of resistance, with 37.6% of the bacterial isolates resistant to key antibiotics. Resistance was associated with geographical area [adjusted odds ratio (AOR) for Central/South Italy compared to North Italy: 6.775, p = 0.002], and with early use of systemic steroids (AOR 6.971, p = 0.018).ConclusionsIn patients deceased with COVID-19, a large proportion of BSI are caused by antibiotic-resistant bacteria. Early steroid use may facilitate this occurrence.