bluuebunny/crossref_metadata_2025_split huggingface dataset:
The bile acid‐activated retinoic acid response in dendritic cells is involved in food allergen sensitization
Authors: Wu Renlan , Yuan Xiefang , Li Xingjie , Ma Ning , Jiang Hongyu , Tang Hongmei , Xu Guofeng , Liu Zhigang , Zhang Zongde 
Published: August 2021

AbstractBackgroundAlteration of commensal microbiota is highly correlated with the prevalence of allergic reactions to food in the gastrointestinal tract. The mechanisms by which microbiota modulate food allergen sensitization in the mucosal site are not fully understood.MethodsWe generate DCs specific knockout of retinoic acid receptor α (Rara) gene mice (DC KO Rara) to evaluate food sensitization. The bile acid‐activated retinoic acid response was evaluated by flow cytometry, real‐time RT‐PCR and Illumina transcriptome sequencing. The global effect of Abx treatment on BA profiles in the mucosal lymph tissue mLN in mice was examined by UPLC‐MS analysis.ResultsIn this study, we demonstrate that depletion of commensal gut bacteria leads to enhanced retinoic acid (RA) signaling in mucosal dendritic cells (DCs). RA signaling in DCs is required for the production of food allergen‐specific IgE and IgG1. Antibiotics induced an enlarged bile acid (BA) pool, and dysregulated BA profiles contributed to enhanced RA signaling in mucosal DCs. BA‐activated RA signaling promoted DC upregulation of interferon I signature, RA signature, OX40L, and PDL2, which may lead to T helper 2 differentiation of CD4+ T cells. BA‐activated RA signaling involved the farnesoid X receptor and RA receptor α (RARa) interaction. Depletion of bile acid reduces food allergen specific IgE and IgG1 levels in mice.ConclusionOur research unveils a mechanism of food sensitization modulated by BA‐RA signaling in DCs, which suggests a potential new approach for the intervention of food allergic reactions.
Clinical benefit for cryopreservation of single human spermatozoa for ICSI: A systematic review and meta‐analysis
Authors: Huang Chuan , Gan Run‐Xin , Hu Jian‐Lin , Liu Feng , Hong Yan , Zhu Wen‐Bing , Li Zheng 
Published: August 2021

AbstractBackgroundSystematic reviews have focused on sperm recovery and post‐thaw parameters after cryopreservation, but there is no information on the associated clinical outcomes. In recent years, an increasing number of studies have reported cryopreservation of a single sperm due to the importance of fertility preservation.ObjectivesTo assess whether the cryopreservation of single human spermatozoa improves clinical outcomes in patients with azoospermia or severe oligospermia.Materials and methodsWe conducted an extensive literature search using the following databases: CENTRAL, CNKI, Cochrane Systematic Reviews, EMBASE, MEDLINE, PUBMED, and Web of Science for relevant studies published through December 31, 2019. We calculated the pooled proportions of cryopreservation of a single human spermatozoon to assess the recovery, survival, fertilization, pregnancy, miscarriage, and delivery rates. Subgroup analyses were performed for the following covariates, (a) different carriers, (b) year of publication, and (c) source of sperm.ResultsWe included 25 studies, which included 13 carriers. The pooled proportion of recovery rate of spermatozoa cryopreserved was 92% (95% CI, 87%–96%), and the survival, fertilization, pregnancy, miscarriage, and delivery rates were 76% (95% CI, 69%–83%), 63% (95% CI, 58%–67%), 57% (95% CI, 39%–74%), 12% (95% CI, 0%–33%), and 40% (95% CI, 12%–71%), respectively. Based on the subgroup analysis, the recovery and survival rates of frozen spermatozoa in a subgroup of different carriers were statistically significant. In the past decade, frozen single human spermatozoon technology has improved the recovery rates of frozen‐thawed spermatozoa. However, the differences in clinical outcomes of frozen spermatozoa in subgroups of different sources of sperm were not statistically significant.Discussion and conclusionThe techniques for single human spermatozoa are feasible and efficient and may benefit patients with severe oligospermia or azoospermia.
Apatinib combined with Keytruda treatment induces apoptosis of gastric carcinoma cells through CES4/miR‐616‐5p/DUSP2 axis
Authors: Zhang Fengli , Yin Yanfen , Xu Wenwen , Zhou Zhou , Sun Xin , Li Ping 
Published: August 2021

AbstractGastric carcinoma (GC) is a highly malignant and heterogeneous tumour. Long non‐coding RNA CES4 is down‐regulated in GC. However, whether CES4 can participate in GC remains unclear; we have carried out research on this topic. GC cells (HGC‐27 and MKN‐7) were treated with anti‐tumour drugs: apatinib combined with Keytruda. Cell viability and apoptosis were detected by CCK‐8 assay and flow cytometry. Gene and protein expression were examined by quantitative real‐time PCR and western blot. Luciferase reporter assay was performed to verify the relationship among CES4, miR‐616‐5p and dual‐specificity phosphatase‐2 (DUSP2). CES4 was highly expressed in the apatinib combined with Keytruda‐treated HGC‐27 and MKN‐7 cells. Apatinib combined with Keytruda treatment repressed cell viability and promoted apoptosis of HGC‐27 and MKN‐7 cells, which was abrogated by CES4 knockdown. Furthermore, CES4 promoted DUSP2 expression by sponging miR‐616‐5p in HGC‐27 and MKN‐7 cells. CES4 knockdown promoted cell viability and inhibited apoptosis of drug‐treated HGC‐27 and MKN‐7 cells by regulating miR‐616‐5p/DUSP2 axis. In conclusion, these data demonstrate that apatinib combined with Keytruda treatment induces apoptosis of GC cells through CES4/miR‐616‐5p/DUSP2 axis. Thus, this work provides the experimental basis for the combination of apatinib and Keytruda as a treatment for GC.
Percutaneous nephrolithotomy – the puncture
Authors: Alken Peter 
Published: August 2021

AbstractObjectiveTo determine what importance is given to the puncture and assistive technologies in percutaneous nephrolithotomy (PNL) in the current urological literature.MethodsPubMed was searched for English publications and reviews for the keywords: ‘percutaneous nephrolithotomy’, ‘percutaneous nephrostomy’, ‘puncture’. The search was limited to the last 5 years, January 2016 until February 2021. Based on 183 abstracts, 121 publications were selected, read, and reviewed. References, older or seminal papers were read and cited if they contributed to a better understanding. A total of 198 references form the basis of this narrative review.ResultsThe puncture is frequently referred to as the most crucial part of PNL. In contrast, the influence of the puncture on the failure rate of PNL and the specific puncture‐related complications seems to be low in the single‐digit percentage range. However, there are no universally accepted definitions and standards measuring the quality of puncture. Consequently, the impact of the puncture on general PNL complications, on stone scores predicting success rates and on learning curves evaluating surgeons’ performance have not been systematically studied. Assistive technologies rely on fluoroscopy and ultrasonography, the latter of which is becoming the preferred imaging modality for monitoring the entire procedure. Needle bending, a problem relevant to all puncture techniques, is not addressed in the urological literature.ConclusionsThe importance attached to puncture in PNL in the current urological literature is subjectively high but objectively low. Some basics of puncture are not well understood in urology. Disciplines other than urology are more actively involved in the development of puncture techniques.
Glucagon‐like peptide‐1 in diabetes care: Can glycaemic control be achieved without nausea and vomiting?
Authors: Borner Tito , Tinsley Ian C. , Doyle Robert P. , Hayes Matthew R. , De Jonghe Bart C. 
Published: August 2021

Introduced less than two decades ago, glucagon‐like peptide‐1 receptor agonists rapidly reshaped the field of Type 2 diabetes mellitus (T2DM) care by providing glycaemic control in tandem with weight loss. However, FDA‐approved GLP‐1 receptor agonists are often accompanied by nausea and emesis and, in some lean T2DM patients, by undesired anorexia. Importantly, the hypophagic and emetic effects of GLP‐1 receptor agonists are caused by activation of central GLP‐1 receptors. This review summarizes two different approaches to mitigate the incidence and severity of nausea and emesis related to GLP‐1 receptor agonists: conjugation with vitamin B12, or related corrin ring‐containing compounds (‘corrination’), and development of dual agonists of GLP‐1 receptors with glucose‐dependent insulinotropic polypeptide (GIP). Such approaches could lead to the generation of GLP‐1 receptor agonists with improved therapeutic efficacy, thus decreasing treatment attrition, increasing patient compliance and extending treatment to a broader population of T2DM patients. The data reviewed show that it is possible to pharmacologically separate the emetic effects of GLP‐1 receptor agonists from their glucoregulatory action.LINKED ARTICLESThis article is part of a themed issue on GLP1 receptor ligands (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.4/issuetoc
Metabolomics reveals biomarkers in human urine and plasma to predict cytochrome P450 2D6 (CYP2D6) activity
Authors: Magliocco Gaëlle , Desmeules Jules , Matthey Alain , Quirós‐Guerrero Luis M. , Bararpour Nasim , Joye Timothée , Marcourt Laurence , Queiroz Emerson F. , Wolfender Jean‐Luc , Gloor Yvonne , Thomas Aurélien , Daali Youssef 
Published: August 2021

Background and PurposeIndividualized assessment of cytochrome P450 2D6 (CYP2D6) activity is usually performed through phenotyping following administration of a probe drug to measure the enzyme's activity. To avoid any iatrogenic harm (allergic drug reaction, dosing error) related to the probe drug, the development of non‐burdensome tools for real‐time phenotyping of CYP2D6 could significantly contribute to precision medicine. This study focuses on the identification of markers of the CYP2D6 enzyme in human biofluids using an LC‐high‐resolution mass spectrometry‐based metabolomic approach.Experimental ApproachPlasma and urine samples from healthy volunteers were analysed before and after intake of a daily dose of paroxetine 20 mg over 7 days. CYP2D6 genotyping and phenotyping, using single oral dose of dextromethorphan 5 mg, were also performed in all participants.Key ResultsWe report four metabolites of solanidine and two unknown compounds as possible novel CYP2D6 markers. Mean relative intensities of these features were significantly reduced during the inhibition session compared with the control session (n = 37). Semi‐quantitative analysis showed that the largest decrease (−85%) was observed for the ion m/z 432.3108 normalized to solanidine (m/z 398.3417). Mean relative intensities of these ions were significantly higher in the CYP2D6 normal–ultrarapid metabolizer group (n = 37) compared with the poor metabolizer group (n = 6). Solanidine intensity was more than 15 times higher in CYP2D6‐deficient individuals compared with other volunteers.Conclusion and ImplicationsThe applied untargeted metabolomic strategy identified potential novel markers capable of semi‐quantitatively predicting CYP2D6 activity, a promising discovery for personalized medicine.
The survival and proliferation of osteosarcoma cells are dependent on the mitochondrial BIG3‐PHB2 complex formation
Authors: Toki Shunichi , Yoshimaru Tetsuro , Matsushita Yosuke , Aihara Hitoshi , Ono Masaya , Tsuneyama Koichi , Sairyo Koichi , Katagiri Toyomasa 
Published: August 2021

AbstractPrevious studies reported the critical role of the brefeldin A–inhibited guanine nucleotide exchange protein 3–prohibitin 2 (BIG3‐PHB2) complex in modulating estrogen signaling activation in breast cancer cells, yet its pathophysiological roles in osteosarcoma (OS) cells remain elusive. Here, we report a novel function of BIG3‐PHB2 in OS malignancy. BIG3‐PHB2 complexes were localized mainly in mitochondria in OS cells, unlike in estrogen‐dependent breast cancer cells. Depletion of endogenous BIG3 expression by small interfering RNA (siRNA) treatment led to significant inhibition of OS cell growth. Disruption of BIG3‐PHB2 complex formation by treatment with specific peptide inhibitor also resulted in significant dose‐dependent suppression of OS cell growth, migration, and invasion resulting from G2/M‐phase arrest and in PARP cleavage, ultimately leading to PARP‐1/apoptosis‐inducing factor (AIF) pathway activation–dependent apoptosis in OS cells. Subsequent proteomic and bioinformatic pathway analyses revealed that disruption of the BIG3‐PHB2 complex might lead to downregulation of inner mitochondrial membrane protein complex activity. Our findings indicate that the mitochondrial BIG3‐PHB2 complex might regulate PARP‐1/AIF pathway–dependent apoptosis during OS cell proliferation and progression and that disruption of this complex may be a promising therapeutic strategy for OS.
Inflammatory cytokine responses in children with asymptomatic malaria infection living in rural, semi-urban and urban areas in south-eastern Gabon
Authors: Mbani Mpega Ntigui Chérone Nancy , Oyegue-Liabagui Sandrine Lydie , Kouna Lady Charlene , Imboumy Karl Roméo , Tsafack Tegomo Nathalie Pernelle , Okouga Alain Prince , Ontoua Seinnat , Lekana-Douki Jean-Bernard 
Published: August 2021

Abstract
Cytokines are soluble mediators of the immune response, and their evolution influences the disease outcome. Gaining knowledge on cytokines has become important, as they can constitute biomarkers allowing the diagnosis of malaria and preventing severe forms of the disease. Here, we investigated 10 cytokines and their circulating levels in asymptomatic Gabonese children with Plasmodium falciparum infection living in urban, semi-urban and rural areas. Blood samples were collected from 273 schoolchildren (153 uninfected and 120 infected) aged 6 to 192 months. Hematological parameters were determined and P. falciparum diagnosis was performed using a rapid diagnosis test, microscopy and nested polymerase chain reaction (PCR). Plasma pro- [interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-12p70, IL-17A and IL-22] and anti-inflammatory [IL-10, IL-4, IL-13 and transforming growth factor (TGF)-β] cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA) and compared between asymptomatic-infected and uninfected children. Results revealed that without distinction of area, IL-10 and IL-6 levels were higher in infected compared to uninfected children; however, the pro- and anti-inflammatory ratios (IL-6/IL-10 and TNF-α/IL-10) were similar. Furthermore, with area distinction significantly elevated levels of IL-10 in these asymptomatic children were always accompanied by either significantly low or high levels of a proinflammatory cytokine. Also, comparison between asymptomatic-infected children from the three areas showed significantly lower IL-17A, IL-22 and TGF-β levels in urban area compared to semi-urban and rural areas. These results suggest that asymptomatic malaria infections induce significantly high inflammatory cytokine levels without modifying the balanced between pro- and anti-inflammatory cytokines and underline the higher exposure to infections of children in rural areas.
Prospects of antibodies targeting CD47 or CD24 in the treatment of glioblastoma
Authors: Wu Hao , Liu Jialin , Wang Zhifei , Yuan Wen , Chen Ling 
Published: August 2021

AbstractGlioma is a malignant tumor with the highest incidence among all brain tumors (about 46% of intracranial tumors) and is the most common primary intracranial tumor. Among them, glioblastoma (GBM) is highly malignant and is one of the three refractory tumors with the highest mortality rate in the world. The survival time from glioblastoma diagnosis to death is only 14–16 months for patients with standard treatment such as surgery plus radiotherapy and chemotherapy. Due to its high malignancy and poor prognosis, in‐depth studies have been conducted to explore effective therapeutic strategies for glioblastoma. In addition to the conventional surgery, radiotherapy, and chemotherapy, the glioblastoma treatments also include targeted therapy, immunotherapy, and electric field treatment. However, current treatment methods provide limited benefits because of the heterogeneity of glioblastoma and the complexity of the immune microenvironment within a tumor. Therefore, seeking an effective treatment plan is imperative. In particular, developing an active immunotherapy for glioblastoma has become an essential objective in the field. This article reviews the feasibility of CD47/CD24 antibody treatment, either individually or in combination, to target the tumor stem cells and the antitumor immunity in glioblastoma. The potential mechanisms underlying the antitumor effects of CD47/CD24 antibodies are also discussed.
Interposition of a biological mesh may not affect the rate of rectovaginal fistula after excision of large rectovaginal endometriotic nodules: a pilot study of 209 patients
Authors: Roman Horace , Pontré Jennifer , Braund Sophia , Khalil Haitham , Klapczynski Clemence , Hennetier Clotilde , Bridoux Valérie , Tuech Jean‐Jacques 
Published: August 2021

AbstractAimThe aim of this work was to assess whether placement of a biological mesh (Permacol®) between the vaginal and rectal sutures reduces the rate of rectovaginal fistula in patients with deep rectovaginal endometriosis.MethodWe report a retrospective, comparative study enrolling patients with vaginal infiltration of more than 3 cm in diameter and rectal involvement in two centres. They benefited from complete excision of rectovaginal endometriotic nodules with or without a biological mesh placed between the vaginal and rectal sutures. The rate of rectovaginal fistula was compared between the two groups.ResultsTwo hundred and nine patients were enrolled: 42 patients underwent interposition of biological mesh (cases) and 167 did not (controls). Ninety‐two per cent of cases and 86.2% of controls had rectal infiltration more than 3 cm in diameter. Cases underwent rectal disc excision more frequently (64.3% vs. 49.1%) and had a smaller distance between the rectal staple line and the anal verge (4.4 ± 1.4 cm vs. 6 ± 2.9 cm). Rectovaginal fistulas occurred in 4 cases (9.5%) and 12 controls (7.2%). Logistic regression analyses revealed no difference in the rate of rectovaginal fistula following the use of mesh (adjusted OR 1.6, 95% CI 0.3–9.5). A distance of less than 7 cm between the rectal staple line and the anal verge was found to be an independent risk factor for the development of rectovaginal fistula (adjusted OR 15.1, 95% CI 1.7–132).ConclusionOur results suggest that the placement of a biological mesh between the vagina and rectal sutures may not affect the rate of formation of postoperative rectovaginal fistula following excision of deep infiltrating rectovaginal endometriosis.
Advanced heart failure and heart transplantation in adult congenital heart disease in the current era
Authors: de la Rosa Angelo L. , Singer‐Englar Tahli , Tompkins Rose O. , Patel Jignesh K. , Kobashigawa Jon A. , Kittleson Michelle M. 
Published: August 2021

AbstractBackgroundAdults with congenital heart disease (ACHD) may undergo heart transplantation (HTx) despite increased risk of poor short‐term outcomes due to factors including surgical complexity and antibody sensitization. We assessed the clinical characteristics and outcomes of patients with ACHD in the current era referred for HTx at a single high‐volume transplant center.MethodsFrom 2010 to 2020, 37 ACHD patients were evaluated for HTx. ACHD HTx recipients were compared to non‐ACHD HTx recipients matched for age, sex, listing status, and prior cardiac surgery.ResultsOf the 37 patients with ACHD, eight (21.6%) were declined for HTx. Of 29 ACHD patients listed, 19 (65.5%) underwent HTx. Compared with non‐ACHD HTx controls, the ACHD HTx recipients had more treated cellular (21.1% vs. 15.8%, P = .010) and antibody‐mediated (15.8% vs. 10.5%, P = .033) rejection. There was no difference in hospital readmission or allograft vasculopathy at 1 year. There was a nonsignificant higher 1‐year mortality in ACHD HTx recipients (21.1% vs. 7.9%, P = .21).ConclusionAt a high‐volume transplant center, ACHD patients undergoing HTx appear to have a marginally higher risk of rejection, but no significant increase in 1‐year mortality. With careful selection and management, HTx for patients with ACHD may be feasible in the current era.
Clinical and histopathological evaluation of 50 acantholytic cutaneous squamous cell carcinomas: Analysis outcome in a retrospective case‐control study
Authors: Conde‐Ferreirós Alberto , Moyano‐Bueno David , Santos‐Briz Ángel , Revelles‐Peñas Leonor , Revilla‐Nebreda David , Becerril‐Andrés Sara , Román‐Curto Concepción , Cañueto Javier 
Published: August 2021

AbstractBackgroundAcantholytic cutaneous squamous cell carcinomas (aCSCCs) have been classically considered as a high‐risk variant of CSCC. However, more recent studies show that aCSCC does not confer more aggressiveness. This study aims to establish whether the prognosis of the aCSCC is worse than that of the non‐acantholytic (naCSCC) or not.MethodsRetrospective case‐control study with 50 aCSCCs and 50 naCSCCs. For each aCSCC, an naCSCC with similar high‐risk features to the aCSCC but with no acantholysis was selected. Prognosis between both groups was compared.ResultsThe mean age was 86 years (SD 9.61). Sixty‐one patients were men. Thirty‐nine CSCCs were located in high‐risk head and neck areas. Twenty CSCCs exhibited a poor degree of differentiation, and 36 showed an infiltrative growth pattern. The tumor diameter was 18.71 mm (interquartile range, IQR 35), and the tumor thickness was 6.72 mm (IQR 15.50). Twelve CSCCs exhibited perineural infiltration, and eight CSCCs exhibited invasion beyond the subcutaneous fat. Positive margins after excision of the tumor in 22 aCSCCs vs eight naCSCCs (P < 0.02). Nineteen poor‐prognosis events were observed (local recurrence, lymph node metastasis, and death from CSCC). However, no differences were observed between both groups when comparing poor‐prognosis events.ConclusionThe proportion of unfavorable events is similar in aCSCC and naCSCC. The acantholytic histopathological subtype is not associated with a poorer prognosis than the non‐acantholytic CSCC in our cohort.