bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case report: Mild phenotype of a patient with vascular Ehlers–Danlos syndrome and COL3A1 duplication mutation without alteration in the [Gly-X-Y] repeat sequence
Authors: Hayashi Shujiro , Yamaguchi Tomomi , Kosho Tomoki , Igawa Ken 
Published: November 2022

Background: Vascular-type Ehlers–Danlos syndrome (vEDS) is an autosomal dominant inherited disorder caused by a deficit in collagen III as a result of heterogeneous mutations in the α1 type III collagen gene (COL3A1). Patients with vEDS often experience the first major complications in their early 20s and &gt;80% have at least one complication by their 40s, reducing their average life expectancy to 48 years. Most commonly, vEDS variants are heterozygous missense substitutions of a base-pair encoding a glycine (Gly) residue of the [Gly-X-Y] repeat of the COL3A1 protein. When a peptide chain derived from a mutant allele is present in the procollagen triple helical structure, the helical structure cannot be maintained. Therefore, typically, the mutated collagen peptide induces a dominant negative effect on procollagen production. We reported the case of a patient with vEDS and a unique novel duplication mutation without alteration in the [Gly-X-Y] triplet repeat sequence.Case presentation: A 58-year-old man developed a sudden disorder of consciousness and abdominal pain and was consequently taken to a nearby hospital, where an intra-abdominal aneurysm was found, in addition to mild small joint hypermobility and acrogeria. There has been no history of spontaneous pneumothorax, dislocation, or subcutaneous hematoma. The analysis of genomic DNA from a blood sample identified a likely pathogenic in-frame duplication mutation in the COL3A1 gene coding region. Interestingly, this mutation is not expected to alter the [Gly-X-Y] triplet repeat sequence. We verified the mutation’s pathogenicity by performing an analysis of synthetic procollagen from cultured skin fibroblasts, electron microscopy, and mRNA expression analysis of unfolded protein response sensors for endoplasmic reticulum (ER) stress.Conclusion: Although the clinical findings of the case were mild, when compared to typical vEDS, decreased α1 collagen III levels and morphological abnormalities of the collagenous bundles were observed in the patient samples when compared with the normal control samples. Our evidence supports the conclusion that this variant is pathogenic. However, unlike the common vEDS, ER stress was not observed, and the mild phenotype presentation was suggested to be due to the unique mutation, allowing the triple helical structure to be maintained to a certain extent.
GOLM1 is related to the inflammatory/immune nature of uveal melanoma and acts as a promising indicator for prognosis and immunotherapy response
Authors: Liang Xin , Yin Yu , Li Ning 
Published: November 2022

Purpose: Inflammatory/immune-related features are associated with the immunotherapy and prognosis of uveal melanoma (UVM). In this study, we systematically analyzed the correlation between GOLM1 and the inflammatory/immune nature of UVM and explored its potential value in predicting prognosis and guiding immunotherapy for UVM patients.Methods: A total of 143 UVM patients were enrolled in the current study. The differentially expressed genes between the GOLM1-low expression (LEXP) and GOLM1-high expression (HEXP) subgroups were calculated by the “limma” package and further annotated to reveal the key pathways by the “ClusterProfiler” package. Immunocyte infiltration was evaluated by single-sample gene set enrichment analysis, while the potential response to immunotherapy was realized by subclass mapping analysis. Moreover, tumor tissue sections from 23 UVM patients were collected and stained for GOLM1 (1:300; cat# DF8100, Affinity Biosciences), PD-L1 (1:250; cat# ab213524, Abcam), PD-1 (1:100; cat# ab52587, Abcam), CTLA-4 (1:300; cat# DF6793, Affinity Biosciences), and IFN-γ (1:300; cat# DF6045, Affinity Biosciences).Results: We found that higher expression of GOLM1 correlated with an unfavorable prognosis in UVM patients. Multivariate Cox regression analysis suggested that GOLM1 served as a prognostic factor independent of clinicopathological parameters. Notably, we found that the expression of PD-1, PD-L1, IFN-γ, and CTLA4 was higher in the GOLM1-high subgroup than in the GOLM1-low expression subgroup at the mRNA level and was subsequently validated at the protein level by immunohistochemistry. Gene pattern and SubMap analyses confirmed the indicator role of GOLM1 in predicting immunotherapy response in UVM.Conclusion: Taken together, GOLM1 is a novel prognostic marker, and it can be employed to predict the overall survival outcomes and treatment responses of anti-PD-1/PD-L1 and anti-CTLA4 therapies for UVM patients.
Detection and management of postpartum haemorrhage: Qualitative evidence on healthcare providers' knowledge and practices in Kenya, Nigeria, and South Africa
Authors: Akter Shahinoor , Forbes Gillian , Miller Suellen , Galadanci Hadiza , Qureshi Zahida , Fawcus Sue , Justus Hofmeyr G. , Moran Neil , Singata-Madliki Mandisa , Amole Taiwo Gboluwaga , Gwako George , Osoti Alfred , Thomas Eleanor , Gallos Ioannis , Mammoliti Kristie-Marie , Coomarasamy Arri , Althabe Fernando , Lorencatto Fabiana , Bohren Meghan A. 
Published: November 2022

BackgroundPostpartum haemorrhage (PPH) is the leading cause of maternal death globally. Most PPH deaths can be avoided with timely detection and management; however, critical challenges persist. A multi-country cluster-randomised trial (E-MOTIVE) will introduce a clinical care bundle for early detection and first-response PPH management in hospital settings. This formative qualitative study aimed to explore healthcare providers' knowledge and practices of PPH detection and management after vaginal birth, to inform design and implementation of E-MOTIVE.MethodsBetween July 2020–June 2021, semi-structured qualitative interviews were conducted with 45 maternity healthcare providers (midwives, nurses, doctors, managers) of nine hospitals in Kenya, Nigeria, and South Africa. A thematic analysis approach was used.ResultsFour key themes were identified, which varied across contexts: in-service training on emergency obstetric care; limited knowledge about PPH; current approaches to PPH detection; and current PPH management and associated challenges. PPH was recognised as an emergency but understanding of PPH varied. Early PPH detection was limited by the subjective nature of visual estimation of blood loss. Lack of expertise on PPH detection and using visual estimation can result in delays in initiation of PPH management. Shortages of trained staff and essential resources, and late inter-hospital referrals were common barriers to PPH management.ConclusionThere are critical needs to address context-specific barriers to early and timely detection and management of PPH in hospital settings. These findings will be used to develop evidence-informed implementation strategies, such as improved in-service training, and objective measurement of blood loss, which are key components of the E-MOTIVE trial (Trial registration: ClinicalTrials.gov: NCT04341662).
Evolutionary analyses of polymeric immunoglobulin receptor (pIgR) in the mammals reveals an outstanding mutation rate in the lagomorphs
Authors: Neves Fabiana , de Sousa-Pereira Patrícia , Melo-Ferreira José , Esteves Pedro J. , Pinheiro Ana 
Published: November 2022

BackgroundThe transcytosis of polymeric immunoglobulins, IgA and IgM, across the epithelial barrier to the luminal side of mucosal tissues is mediated by the polymeric immunoglobulin receptor (pIgR). At the luminal side the extracellular ligand binding region of pIgR, the secretory component (SC), is cleaved and released bound to dimeric IgA (dIgA), protecting it from proteolytic degradation, or in free form, protecting the mucosa form pathogens attacks. The pIgR was first cloned for rabbit in early 1980’s and since then has been described for all vertebrates, from fish to mammals. The existence of more than one functional pIgR alternative-spliced variant in the European rabbit, the complete pIgR as other mammals and a shorter pIgR lacking two SC exons, raised the question whether other lagomorphs share the same characteristics and how has thePIGRgene evolved in these mammals.ResultsTo investigate these questions, we sequenced expressed pIgR genes for other leporid genus,Lepusspp., and obtained and aligned pIgR sequences from representative species of all mammalian orders. The obtained mammalian phylogeny, as well as the Bayesian inference of evolutionary rates and genetic distances, show that Lagomorpha pIgR is evolving at a higher substitution rate. Codon-based analyses of positive selection show that mammalian pIgR is evolving under strong positive selection, with strong incidence in the domains excised from the rabbit short pIgR isoform. We further confirmed that the hares also express the two rabbit pIgR isoforms.ConclusionsThe Lagomorpha pIgR unique evolutionary pattern may reflect a group specific adaptation. The pIgR evolution may be linked to the unusual expansion of IgA genes observed in lagomorphs, or to neofunctionalization in this group. Further studies are necessary to clarify the driving forces behind the unique lagomorph pIgR evolution.
The development of cortical processing of speech differs between children with cochlear implants and normal hearing and changes with parental singing
Authors: Torppa Ritva , Kuuluvainen Soila , Lipsanen Jari 
Published: November 2022

ObjectiveThe aim of the present study was to investigate speech processing development in children with normal hearing (NH) and cochlear implants (CI) groups using a multifeature event-related potential (ERP) paradigm. Singing is associated to enhanced attention and speech perception. Therefore, its connection to ERPs was investigated in the CI group.MethodsThe paradigm included five change types in a pseudoword: two easy- (duration, gap) and three difficult-to-detect (vowel, pitch, intensity) with CIs. The positive mismatch responses (pMMR), mismatch negativity (MMN), P3a and late differentiating negativity (LDN) responses of preschoolers (below 6 years 9 months) and schoolchildren (above 6 years 9 months) with NH or CIs at two time points (T1, T2) were investigated with Linear Mixed Modeling (LMM). For the CI group, the association of singing at home and ERP development was modeled with LMM.ResultsOverall, responses elicited by the easy- and difficult to detect changes differed between the CI and NH groups. Compared to the NH group, the CI group had smaller MMNs to vowel duration changes and gaps, larger P3a responses to gaps, and larger pMMRs and smaller LDNs to vowel identity changes. Preschoolers had smaller P3a responses and larger LDNs to gaps, and larger pMMRs to vowel identity changes than schoolchildren. In addition, the pMMRs to gaps increased from T1 to T2 in preschoolers. More parental singing in the CI group was associated with increasing pMMR and less parental singing with decreasing P3a amplitudes from T1 to T2.ConclusionThe multifeature paradigm is suitable for assessing cortical speech processing development in children. In children with CIs, cortical discrimination is often reflected in pMMR and P3a responses, and in MMN and LDN responses in children with NH. Moreover, the cortical speech discrimination of children with CIs develops late, and over time and age, their speech sound change processing changes as does the processing of children with NH. Importantly, multisensory activities such as parental singing can lead to improvement in the discrimination and attention shifting toward speech changes in children with CIs. These novel results should be taken into account in future research and rehabilitation.
Combining effect of camellia oil and squalene on hyperlipidemia-induced reproductive damage in male rats
Authors: Xu Qi , Luo Minhui , Cheng Gengjinsheng , Zhong Qi , Guo Yixing , Luo Jianghong 
Published: November 2022

IntroductionCamellia oil (CO), a common edible oil in China, contains a variety of active ingredients. In this study, we explored the combining effect and optimal feeding time of CO and squalene on hyperlipemia-induced reproductive damage rats and probably provided supportive data for use of CO for health benefits.MethodsWe established the hyperlipidaemia-induced reproductive damage model, and then the successfully modeled rats were randomly classified into four groups including a model control (MC) group, a camellia oil (CO) group, a camellia oil + squalene (COS) group, and a sildenafil (SN) group, which were feeding with different subjects during days 30 and 60. The normal (NC) group was fed under the same conditions.ResultsOur results showed that compared with the MC group, the CO, COS, and SN groups could significantly decline the serum TG, TC and LDL-C levels, increase the serum testosterone levels, the sperm counts in epididymidis and organ coefficients of penises, and no pathological change in penis and testis at days 30 and 60. Compared with the pure CO, the mixture of CO and squalene could significantly enhance the effect of decreasing the concentrations of TG, TC, and LDL-C and increasing the serum testosterone level and sperm count of epididymal tail, and the results of day 30 were better than those of day 60.DiscussionCO and squalene have a combining effect on lowering blood lipid, improving the level of testosterone and the number of epididymal tail sperm, and promoting the recovery of erectile and sexual function on hyperlipidemia-induced reproductive damage rats on day 30.
Mid- and long-term changes in satiety-related hormones, lipid and glucose metabolism, and inflammation after a Mediterranean diet intervention with the goal of losing weight: A randomized, clinical trial
Authors: Hernando-Redondo J , Toloba A , Benaiges D , Salas-Salvadó J , Martínez-Gonzalez MA , Corella D , Estruch R , Tinahones FJ , Ros E , Goday A , Castañer O , Fitó M 
Published: November 2022

BackgroundObesity is produced by the enlargement of the adipose tissue. Functioning as an endocrine organ, it releases and receives information through a complex network of cytokines, hormones, and substrates contributing to a low-chronic inflammation environment. Diet and healthy habits play key roles in the prevention of obesity and its related pathologies. In this regard, there is a need to switch to healthier and more appetizing diets, such as the Mediterranean one.ObjectiveTo compare the mid-and long-term effects of two Mediterranean diet (MedDiet) interventions, one energy-reduced plus physical activity promotion versus a non-restrictive diet, on peripheral satiety-related hormones, weight loss, glucose/lipid metabolism, and pro-inflammatory markers in subjects with obesity/overweight and metabolic syndrome.Materials and methodsA randomized, lifestyle intervention was conducted in 23 Spanish centers, with a large cohort of patients presenting metabolic syndrome. Our study is a subproject set in IMIM (Hospital del Mar Research Institute). Participants were men and women, aged 55–75 and 60–75, respectively, who at baseline met at least three metabolic syndrome components. Subjects were assigned to two intervention groups: (1) an intensive lifestyle intervention with an energy-reduced MedDiet and physical activity promotion (intervention group) with the aim of weight loss; and (2) a normocaloric MedDiet (control). We quantified in a subsample of 300 volunteers from Hospital del Mar Research Institute (Barcelona), following analytes at baseline, 6 months, and 1 year: glucose, HbA1c, triglycerides, total cholesterol, high-density lipoprotein cholesterol, LDL cholesterol, C-peptide, ghrelin, GLP-1, glucagon, insulin, leptin, PAI-1, resistin, and visfatin. Anthropometric and classical cardiovascular risk factors were also determined. A multivariate statistical model was employed to compare the two groups. Linear mixed-effect models were performed to compare changes in risk factors and biomarkers between intervention groups and over time.ResultsCompared to participants in the control group, those in intervention one showed greater improvements in weight, waist circumference, insulin (P &lt; 0.001), glucose metabolism-related compounds (P &lt; 0.05), triglyceride-related lipid profile (P &lt; 0.05), leptin, blood pressure, and pro-inflammatory markers such as PAI-1 (P &lt; 0.001) at mid-and/or long-term. High-sensitivity C-reactive protein, resistin, and vifastin also decreased in both groups.ConclusionA weight loss intervention employing a hypocaloric MedDiet and physical activity promotion has beneficial effects on adiposity, glucose metabolism, lipid profile, leptin, and pro-inflammatory markers, such as PAI-1 in both mid-and long-term.
Comparison of laparoscopic and open pancreaticoduodenectomy for the treatment of distal cholangiocarcinoma: A propensity score matching analysis
Authors: Zhu Yuwen , Zu Guangchen , Wu Di , Zhang Yue , Yang Yang , Wu Han , Chen Xuemin , Chen Weibo 
Published: November 2022

BackgroundThere are few studies comparing the oncological outcomes of laparoscopic pancreaticoduodenectomy (LPD) and open pancreaticoduodenectomy (OPD) for distal cholangiocarcinoma (DCC). Our objective was to assess the short-term efficacy and long-term survival of LPD and OPD in patients with DCC.MethodsThe data of 124 DCC patients who underwent LPD or OPD at the Third Affiliated Hospital of Soochow University from May 2010 to May 2021 were retrospectively analyzed. Propensity score matching was performed to balance the two groups of baseline characteristics. After 1:1 matching, the overall survival (OS) of the two groups was compared by the Kaplan−Meier method. Univariate and multivariate Cox regression analyses were used to identify independent predictors of OS.ResultsThe original cohort consisted of 124 patients. Nineteen patients were excluded because of incomplete baseline or follow-up data, and the remaining 105 patients were divided into two cohorts (45 in the LPD group and 60 in the OPD group). The LPD group showed more favorable results in OS analysis (LPD vs. OPD, 56.4 [46.2-66.5] vs. 48.9 [36.4-61.4], months, P=0. 01). PSM analysis identified 30 pairs of patients, and differences between matching groups were still significant (LPD vs. OPD, 67.9[58.2-77.6] vs. 47.4[31.4-67.5], months, P=0.002). Moreover, the LPD group experienced less intraoperative bleeding (LPD vs. OPD, 292.67 vs. 519.17 mL, P=0.002). Univariate analysis showed that surgical modality (P=0.012), carbohydrate antigen 19-9 (P=0.043), carcinoembryonic antigen (P=0.003), neutrophil-to-lymphocyte ratio (P=0.012), blood transfusion (P=0.031), clinically relevant postoperative pancreatic fistula (P&lt;0.001) and lymphatic metastasis (P=0.004) were predictors of OS. Multivariate Cox analysis demonstrated that carbohydrate antigen 19-9 (P=0.048), carcinoembryonic antigen (P=0.031) and lymphatic metastasis (P=0.023) were independent predictive factors of OS. However, adjuvant therapy had no significant effect on the OS of DCC patients after radical pancreaticoduodenectomy (P&gt;0.05).ConclusionsFor DCC patients, LPD may be a more recommended procedure because of its advantages over OPD in terms of intraoperative bleeding and long-term survival.
A retrospective study on the characteristics of renal pathological grades in HSPN children with mild to moderate proteinuria
Authors: Cao Yan , Shen Tian , Li Yongzhen , Shuai Lanjun , Chen Qiaoping , Mo Shuanghong , Li Canlin , Li Xiaoyan , Wang Ying , Wu Xiaochuan 
Published: November 2022

ObjectiveTo investigate the characteristics of renal pathological grades in Henoch–Schönlein purpura nephritis (HSPN) children with mild to moderate proteinuria and the correlation between pathological grade and severity of proteinuria among this population.MethodsHSPN children who were presented with mild (150 mg &lt;24 h urinary protein &lt;25 mg/kg) to moderate (25 mg/kg ≤24 h urinary protein &lt;50 mg/kg) proteinuria and performed renal biopsy without steroid ± immunosuppressant treatment in the Second Xiangya Hospital between January 2010 and March 2021 were involved. We retrospectively analyzed the correlation between age, disease course, degree of proteinuria, type of immunoglobulin deposits, C3 deposits in glomeruli and renal pathological grade.Results(1) 72 HSPN children including 46 boys and 26 girls were included, with a mean age of onset of 9.01 ± 2.65 years old. The majority of these patients (62.5%) had a disease course between 1 week to 1 month. 51 patients presented with mild proteinuria and 21 patients with moderate proteinuria. (2) Renal biopsy results showed that ISKDC Grade IIIa were both predominant in mild proteinuria group (25, 49%) and moderate proteinuria group (11, 52.4%). 32 patients had grade II (44.4%), 2 had grade IIIb (2.8%), 1 had grade IV (1.4%), and 1 had grade VI (1.4%). There was no correlation between age, disease course and renal pathological grade (p &gt; 0.05). (3) In patients with mild proteinuria (n = 51), 27 (52.9%) HSPN children had a pathological grade ≥ grade III. In patients with moderate proteinuria (n = 21), 13 (61.9%) HSPN children had grade ≥ III. There was no significant difference in the proportion of renal pathological grade between the 2 groups (p &gt; 0.05). (4) There was no significant correlation between glomerular C3 deposits or immunoglobulin deposit types and renal pathological grade (p = 0.776 and p = 0.056 respectively).ConclusionIn HSPN children with mild to moderate proteinuria, longer disease course or heavier urinary protein level is not completely parallel with higher renal pathological grade. ISKDC grade IIIa is the most common pathological grade. Clinicians should pay great attention to the renal injury in patients with mild to moderate proteinuria.