bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and pathologic characteristics of appendiceal neuroendocrine neoplasms diagnosed during pregnancy
Authors: Twito Orit , Akirov Amit , Rosenblum Rachel Chava , Herzberg Dana , Oleinikov Kira , Rotman-Pikielny Pnina , Grozinsky-Glasberg Simona 
Published: February 2023

IntroductionAlthough appendicitis occurs in approximately 1:1000 pregnancies, appendiceal neuroendocrine neoplasm (ANEN) diagnosis during pregnancy is very rare. Data on presentation, treatment and prognosis is scarce.AimTo describe ANEN cases diagnosed during pregnancy.Materials and methodsA retrospective appraisal of 7 consecutive ANEN patients diagnosed during pregnancy from four Israeli tertiary medical centers and comparison with 17 cases described in the literature from 1965-2021.ResultsAge at ANEN diagnosis was 26.4 ± 3.5 years (range 21-33). Patients were diagnosed between gestational weeks 6-40, most frequently in the third trimester (53%). The most common presenting symptom was abdominal pain. Tumor size was 14.3 ± 8.9mm (range 3-45mm). In patients from our series appendiceal base involvement was reported in 2/7; mesoappendiceal invasion in 5/7; lympho-vascular invasion in 2/7. Ki67 staining was reported in 6/7 cases and ranged from 1-10%. Pathology details were lacking in most of the previously published cases. All 7 pregnancies in our series resulted in term delivery with no complications, whereas in historical cases there were one first trimester abortion, one ectopic pregnancy, and one stillbirth. Right hemicolectomy was performed in 5/7 patients in our series and reported in 2/17 historical cases. All hemicolectomies were performed after delivery, 3-16 months after appendectomy. Local metastases were reported in two cases. Follow-up duration was 7-98 months for our patients and 3-48 months in 5 historical cases. No disease recurrence, distant metastases or mortality were noted.ConclusionsTo the best of our knowledge, this is the largest series describing the extremely rare diagnosis of ANEN during pregnancy. Although pathologic characteristics varied, pregnancy outcomes were usually favorable and long-term prognosis was excellent. This data may suggest that a conservative approach to patients with ANEN diagnosis during pregnancy can be considered.
Association between serum total testosterone levels and metabolic syndrome among adult women in the United States, NHANES 2011–2016
Authors: Liu Chenning , Zhao Meiduo , Zhao Yonghua , Hu Yuanjia 
Published: February 2023

ObjectiveTo investigate the association between serum total testosterone (TT) levels and metabolic syndrome (MetS) or its components among adult women.Methods2,678 women from NHANES 2011-2016 were included in this cross-sectional study. MetS was determined according to the National Cholesterol Education Program Adult Treatment Panel III guidelines. The association between serum TT levels and MetS was evaluated by two logistics regression models and the adjusted restricted cubic spline (RCS). Stratified analysis and sensitive analysis were also conducted.ResultsContinuous TT levels were negatively associated with the occurrence of MetS, and the ORs associated with per SD increase in ln TT were 0.70 (95%CI: 0.58-0.85) in 2011-2014 and 0.56 (95%CI: 0.39-0.79) in 2015-2016 in Model A. High TT group were less likely to have MetS (OR=0.60, 95%CI: 0.45-0.80 in 2011-2014 and OR=0.50, 95%CI: 0.32-0.78 in 2015-2016) when compared to the low TT group. When TT levels were divided into quartiles, TT levels were negatively correlated with the incidence of MetS (p for trend &lt; 0.001). Similar trend was observed in Model B. Multivariate-adjusted logistic regression with RCS exhibited that TT had a L-shaped dose–response association with MetS or its components. Interaction analyses revealed that women who were less than 50 years old (OR=0.37, 95%CI: 0.22, 0.63), with depression (OR=0.50, 95%CI: 0.29, 0.87) or being smokers (OR=0.37, 95%CI: 0.23, 0.54) showed lower ORs than those who were over 50 years old (OR=0.66, 95%CI: 0.40, 1.09), without depression (OR=0.59, 95%CI: 0.41, 0.85) or non-smokers (OR=0.59, 95%CI: 0.39, 0.89) when measure the association between ln TT and the occurrence of MetS.ConclusionsOur study indicated that TT levels are negatively correlated with the occurrence of MetS, with interaction effects of age, smoke behaviors, and depressive status.
F8 gene inversion and duplication cause no obvious hemophilia A phenotype
Authors: Li Shaoying , He Jianchun , Chu Liming , Ren Shuai , He Wenzhi , Ma Xiaoyan , Wang Yanchao , Zhang Mincong , Kong Lingyin , Liang Bo , Li Qing 
Published: February 2023

Hemophilia A (HA, OMIM#306700) is an X-linked recessive bleeding disorder caused by the defects in the F8 gene, which encodes coagulation factor VIII (FVIII). Intron 22 inversion (Inv22) is found in about 45% of patients with severe hemophilia A. Here, we reported a male without obvious hemophilia A phenotype but bearing an inherited segmental variant duplication encompassing F8 as well as Inv22. The duplication was approximately 0.16 Mb and involved from exon 1 to intron 22 of F8. This partial duplication and Inv22 in F8 was first found in the abortion tissue of his older sister with recurrent miscarriage. The genetic testing of his family revealed that his phenotypically normal older sister and mother also had this heterozygous Inv22 and a 0.16 Mb partial duplication of F8, while his father was genotypically normal. The integrity of the F8 gene transcript was verified by sequencing of the adjacent exons at the inversion breakpoint, which explained why this male had no phenotype for hemophilia A. Interestingly, although he had no significant hemophilia A phenotype, the expression of C1QA in his mother, sister, and the male subject was only about half of that in his father and normal population. Our report broadens the mutation spectrum of F8 inversion and duplication and its pathogenicity in hemophilia A.
Anti-inflammatory actions of Pentosan polysulfate sodium in a mouse model of influenza virus A/PR8/34-induced pulmonary inflammation
Authors: Krishnan Ravi , Stapledon Catherine J. M. , Mostafavi Helen , Freitas Joseph R. , Liu Xiang , Mahalingam Suresh , Zaid Ali 
Published: February 2023

IntroductionThere is an unmet medical need for effective anti-inflammatory agents for the treatment of acute and post-acute lung inflammation caused by respiratory viruses. The semi-synthetic polysaccharide, Pentosan polysulfate sodium (PPS), an inhibitor of NF-kB activation, was investigated for its systemic and local anti-inflammatory effects in a mouse model of influenza virus A/PR8/1934 (PR8 strain) mediated infection.MethodsImmunocompetent C57BL/6J mice were infected intranasally with a sublethal dose of PR8 and treated subcutaneously with 3 or 6 mg/kg PPS or vehicle. Disease was monitored and tissues were collected at the acute (8 days post-infection; dpi) or post-acute (21 dpi) phase of disease to assess the effect of PPS on PR8-induced pathology.ResultsIn the acute phase of PR8 infection, PPS treatment was associated with a reduction in weight loss and improvement in oxygen saturation when compared to vehicle-treated mice. Associated with these clinical improvements, PPS treatment showed a significant retention in the numbers of protective SiglecF+ resident alveolar macrophages, despite uneventful changes in pulmonary leukocyte infiltrates assessed by flow cytometry. PPS treatment in PR8- infected mice showed significant reductions systemically but not locally of the inflammatory molecules, IL-6, IFN-g, TNF-a, IL-12p70 and CCL2. In the post-acute phase of infection, PPS demonstrated a reduction in the pulmonary fibrotic biomarkers, sICAM-1 and complement factor C5b9.DiscussionThe systemic and local anti-inflammatory actions of PPS may regulate acute and post-acute pulmonary inflammation and tissue remodeling mediated by PR8 infection, which warrants further investigation.
The immune-metabolic crosstalk between CD3+C1q+TAM and CD8+T cells associated with relapse-free survival in HCC
Authors: Yang Yanying , Sun Lu , Chen Zhouyi , Liu Weiren , Xu Qiyue , Liu Fangming , Ma Mingyue , Chen Yuwen , Lu Yan , Fang Hao , Chen Geng , Shi Yinghong , Wu Duojiao 
Published: February 2023

IntroductionAlthough multiple targeted treatments have appeared, hepatocellular carcinoma (HCC) is still one of the most common causes of cancer-related deaths. The immunosuppressive tumor microenvironment (TME) is a critical factor in the oncogenesis and progression of HCC. The emerging scRNA-seq makes it possible to explore the TME at a high resolution. This study was designed to reveal the immune-metabolic crosstalk between immune cells in HCC and provide novel strategies to regulate immunosuppressive TME.MethodIn this study, we performed scRNA-seq on paired tumor and peri-tumor tissues of HCC. The composition and differentiation trajectory of the immune populations in TME were portrayed. Cellphone DB was utilized to calculate interactions between the identified clusters. Besides, flow cytometry, RT-PCR and seahorse experiments were implemented to explore potential metabolic and epigenetic mechanisms of the inter-cellular interaction.ResultA total of 19 immune cell clusters were identified and 7 were found closely related to HCC prognosis. Besides, differentiation trajectories of T cells were also presented. Moreover, a new population, CD3+C1q+ tumor-associated macrophages (TAM) were identified and found significantly interacted with CD8+ CCL4+T cells. Compared to the peri-tumor tissue, their interaction was attenuated in tumor. Additionally, the dynamic presence of this newly found cluster was also verified in the peripheral blood of patients with sepsis. Furthermore, we found that CD3+C1q+TAM affected T cell immunity through C1q signaling-induced metabolic and epigenetic reprogramming, thereby potentially affecting tumor prognosis.ConclusionOur study revealed the interaction between CD3+C1q+TAM and CD8+ CCL4+T cells and may provide implications for tackling the immunosuppressive TME in HCC.
Characteristics of refined lymphocyte subsets changes in people living with HIV/AIDS during antiretroviral therapy period: An observation from Wuhan, China
Authors: Yuan Rui , Li Ling , Hu Wenjia , Zhuang Ke , Zhang Ejuan , Yan Yajun , Feng Ling , Chen Xiaoping , Cao Qian , Ke Hengning , Gui Xien , Yang Rongrong 
Published: February 2023

BackgroundTo analyze the changing characteristics of continuous monitoring of refined lymphocyte subsets in people living with HIV/AIDS (PLWHA) during ART period.MethodsRefined lymphocyte subsets was continuously monitored using flow cytometry for 173 PLWHA, who were hospitalized in Zhongnan Hospital of Wuhan University from August 17, 2021 to September 14, 2022. The effect of ART status and duration of ART on changes of refined lymphocyte subsets were compared in different groups. Then, the levels of refined lymphocyte subsets in PLWHA treated for more than 10 years were compared to those of 1086 healthy individuals.ResultsIn addition to conventional CD4+ T lymphocytes and CD4+/CD8+ ratio, gradually increasing in numbers of CD3+CD4+CD45RO cells, CD3+CD4+CD45RA cells, CD45RA+CD3+CD4+CD25+CD127low and CD45RO+CD3+CD4+CD25+CD127low cells were found with the increase of ART duration. The number of CD4+CD28+ cells and CD8+CD28+ cells were 174/ul and 233/ul at 6 months post-ART, which gradually increased to 616/ul and 461/ul after ART initiation more than 10 years. Moreover, in ART ≤ 6 months, 6 months-3years, 3-10 years and &gt;10 years groups, the percentage of CD3+CD8+HLA-DR+/CD8 were 79.66%, 69.73%, 60.19% and 57.90%, respectively, and the differences between groups showed statistical significance (F=5.727, P=0.001). For those PLWHA with ART more than 10 years, the levels of CD4+ T lymphocytes, CD3+CD4+CD45RO cells, CD3+CD4+CD45RA cells, CD4+CD28+ cells and CD8+CD28+ cells can increase to levels similar to those of healthy control. However, for those PLWHA with ART more than 10 years, CD4+/CD8+ ratio was 0.86 ± 0.47, which was lower than that of healthy control (0.86 ± 0.47 vs 1.32 ± 0.59, t=3.611, P=0.003); absolute counts and percentage of CD3+CD8+HLA-DR+ cells were 547/ul and 57.90%, which were higher than those of healthy control(547/ul vs 135/ul, t=3.612, P=0.003; 57.90% vs 22.38%, t=6.959, P&lt;0.001).ConclusionPersistent ART can gradually improve the immune status of PLWHA, which is manifested in the increase of lymphocytes, function recovery of lymphocytes and reduction of aberrant activation status of the immune system. After 10 years of standardized ART, most lymphocytes could return to levels of healthy persons, although it may take longer to complete recovery for CD4+/CD8+ ratio and CD3+CD8+HLA-DR+ cells.
Inhibition of tumor necrosis factor receptor 1 and the risk of periodontitis
Authors: Alayash Zoheir , Baumeister Sebastian-Edgar , Holtfreter Birte , Kocher Thomas , Baurecht Hansjörg , Ehmke Benjamin , Reckelkamm Stefan Lars , Nolde Michael 
Published: February 2023

AimTo investigate the effect of genetically proxied inhibition of tumor necrosis factor receptor 1 (TNFR1) on the risk of periodontitis.Materials and methodsGenetic instruments were selected from the vicinity of TNFR superfamily member 1A (TNFRSF1A) gene (chromosome 12; base pairs 6,437,923–6,451,280 as per GRCh37 assembly) based on their association with C-reactive protein (N= 575,531). Summary statistics of these variants were obtained from a genome-wide association study (GWAS) of 17,353 periodontitis cases and 28,210 controls to estimate the effect of TNFR1 inhibition on periodontitis using a fixed-effects inverse method.ResultsConsidering rs1800693 as an instrument, we found no effect of TNFR1 inhibition on periodontitis risk (Odds ratio (OR) scaled per standard deviation increment in CRP: 1.57, 95% confidence interval (CI): 0.38;6.46). Similar results were derived from a secondary analysis that used three variants (rs767455, rs4149570, and rs4149577) to index TNFR1 inhibition.ConclusionsWe found no evidence of a potential efficacy of TNFR1 inhibition on periodontitis risk.
Multi-omics analysis unravels the underlying mechanisms of poor prognosis and differential therapeutic responses of solid predominant lung adenocarcinoma
Authors: Li Feng , Wang Shuaibo , Wang Yaru , Lv Zhuoheng , Jin Donghui , Yi Hang , Fu Li , Zhai Suokai , Xiao Ting , Mao Yousheng 
Published: February 2023

BackgroundSolid predominant adenocarcinoma (SPA) has been reported to be a subtype with poor prognosis and unsatisfactory response to chemotherapy and targeted therapy in lung adenocarcinoma (LUAD). However, the underlying mechanisms remain largely unknown and the suitability of immunotherapy for SPA has not been investigated.MethodsWe conducted a multi-omics analysis of 1078 untreated LUAD patients with clinicopathologic, genomic, transcriptomic, and proteomic data from both public and internal cohorts to determine the underlying mechanisms of poor prognosis and differential therapeutic responses of SPA and to investigate the potential of immunotherapy for SPA. The suitability of immunotherapy for SPA was further confirmed in a cohort of LUAD patients who received neoadjuvant immunotherapy in our center.ResultsAlong with its aggressive clinicopathologic behaviors, SPA had significantly higher tumor mutation burden (TMB) and number of pathways altered, lower TTF-1 and Napsin-A expression, higher proliferation score and a more immunoresistant microenvironment than non-solid predominant adenocarcinoma (Non-SPA), accounting for its worse prognosis. Additionally, SPA had significantly lower frequency of therapeutically targetable driver mutations and higher frequency of EGFR/TP53 co-mutation which was related to resistance to EGFR tyrosine kinase inhibitors, indicating a lower potential for targeted therapy. Meanwhile, SPA was enriched for molecular features associated with poor response to chemotherapy (higher chemoresistence signature score, lower chemotherapy response signature score, hypoxic microenvironment, and higher frequency of TP53 mutation). Instead, muti-omics profiling revealed that SPA had stronger immunogenicity and was enriched for positive biomarkers for immunotherapy (higher TMB and T cell receptor diversity; higher PD-L1 expression and more immune cell infiltration; higher frequency of gene mutations predicting efficacious immunotherapy, and elevated expression of immunotherapy-related gene signatures). Furthermore, in the cohort of LUAD patients who received neoadjuvant immunotherapy, SPA had higher pathological regression rates than Non-SPA and patients with major pathological response were enriched in SPA, confirming that SPA was more prone to respond to immunotherapy.ConclusionsCompared with Non-SPA, SPA was enriched for molecular features associated with poor prognosis, unsatisfactory response to chemotherapy and targeted therapy, and good response to immunotherapy, indicating more suitability for immunotherapy while less suitability for chemotherapy and targeted therapy.
SAMHD1 expression modulates innate immune activation and correlates with ovarian cancer prognosis
Authors: Gutiérrez-Chamorro Lucía , Felip Eudald , Bernat-Peguera Adrià , Ezeonwumelu Ifeanyi Jude , Teruel Iris , Martínez-Cardús Anna , Clotet Bonaventura , Riveira-Muñoz Eva , Romeo Margarita , Margelí Mireia , Ballana Ester 
Published: February 2023

PurposeSAMHD1 is a deoxynucleotide triphosphate (dNTP) triphosphohydrolase which has been proposed as a putative prognostic factor in haematological cancers and certain solid tumours, although with controversial data. Here, we evaluate SAMHD1 function in ovarian cancer, both in vitro and in ovarian cancer patients.MethodsSAMHD1 expression was downregulated in ovarian cancer cell lines OVCAR3 and SKOV3 by RNA interference. Gene and protein expression changes in immune signalling pathways were assessed. SAMHD1 expression in ovarian cancer patients was evaluated by immunohistochemistry and survival analysis was performed according to SAMHD1 expression.ResultsSAMHD1 knockdown induced a significant upregulation of proinflammatory cytokines concomitant to increased expression of the main RNA-sensors, MDA5 and RIG-I, and interferon-stimulated genes, supporting the idea that the absence of SAMHD1 promotes innate immune activation in vitro. To assess the contribution of SAMHD1 in ovarian cancer patients, tumours were stratified in SAMHD1-low and SAMHD1-high expressing tumours, resulting in significantly shorter progression free survival (PFS) and overall survival (OS) in SAMHD1-high expression subgroup (p=0.01 and 0.04, respectively).ConclusionsSAMHD1 depletion correlates with increased innate immune cell signalling in ovarian cancer cells. In clinical samples, SAMHD1-low expressing tumors showed increased progression free survival and overall survival irrespective of BRCA mutation status. These results point towards SAMHD1 modulation as a new therapeutic strategy, able to enhance innate immune activation directly in tumour cells, leading to improved prognosis in ovarian cancer.
Metagenomic next-generation sequencing for the etiological diagnosis of rabies virus in cerebrospinal fluid
Authors: Liu Yong , Mo Xichao , Feng Ye , Willoughby Rodney E. , Weng Xing , Wang Yuyang , Li Xing , Gao Junling , Tian Jinfei , Peng Jie 
Published: February 2023

BackgroundRabies is a highly fatal disease. Once symptoms develop, death usually occurs within days. Survivors were occasionally reported in the literatures. Ante-mortem diagnosis remains a challenge in most rabies endemic countries. A novel, accurate diagnostic assay is highly desirable.MethodsWe used metagenomic next-generation sequencing (mNGS) to examine the cerebrospinal fluid (CSF) samples of a 49-year-old patient with rabies and validated the results by TaqMan PCR and RT-PCR/Sanger sequencing.ResultsMetagenomic next-generation sequencing identified sequence reads uniquely aligned to the rabies virus (RABV). PCR confirmed the presence of the partial RABV N gene in the CSF. Phylogenetic analysis showed that the RABV grouped as an Asian clade, which is the most broadly distributed clade in China.ConclusionMetagenomic next-generation sequencing may be a useful screening tool for the etiological diagnosis of rabies, especially in the absence of timely rabies laboratory testing or in patients with no exposure history.
Detection and identification of fungi in the lower airway of children with and without cystic fibrosis
Authors: O’Connor John B. , Wagner Brandie D. , Harris J. Kirk , Frank Daniel N. , Clabots Diana E. , Laguna Theresa A. 
Published: February 2023

IntroductionAirway infection and inflammation lead to the progression of obstructive lung disease in persons with cystic fibrosis (PWCF). However, cystic fibrosis (CF) fungal communities, known drivers of CF pathophysiology, remain poorly understood due to the shortcomings of traditional fungal culture. Our objective was to apply a novel small subunit rRNA gene (SSU-rRNA) sequencing approach to characterize the lower airway mycobiome in children with and without CF.MethodsBronchoalveolar lavage fluid (BALF) samples and relevant clinical data were collected from pediatric PWCF and disease control (DC) subjects. Total fungal load (TFL) was measured using quantitative PCR, and SSU-rRNA sequencing was used for mycobiome characterization. Results were compared across groups, and Morisita-Horn clustering was performed.Results161 (84%) of the BALF samples collected had sufficient load for SSU-rRNA sequencing, with amplification being more common in PWCF. BALF from PWCF had increased TFL and increased neutrophilic inflammation compared to DC subjects. PWCF exhibited increased abundance of Aspergillus and Candida, while Malassezia, Cladosporium, and Pleosporales were prevalent in both groups. CF and DC samples showed no clear differences in clustering when compared to each other or to negative controls. SSU-rRNA sequencing was used to profile the mycobiome in pediatric PWCF and DC subjects. Notable differences were observed between the groups, including the abundance of Aspergillus and Candida.DiscussionFungal DNA detected in the airway could represent a combination of pathogenic fungi and environmental exposure (e.g., dust) to fungus indicative of a common background signature. Next steps will require comparisons to airway bacterial communities.