bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased High-Risk Human Papillomavirus Viral Load Is Associated With Immunosuppressed Microenvironment and Predicts a Worse Long-Term Survival in Cervical Cancer Patients
Authors: Cao Meng , Wang Ying , Wang Depu , Duan Yixin , Hong Wei , Zhang Nana , Shah Walayat , Wang Yili , Chen Hongwei 
Published: October 2019

Abstract

Objectives
To evaluate the correlation between tumor-infiltrating lymphocytes (TILs) and the viral load of high-risk human papillomavirus (HR-HPV) in cervical cancer patients.

Methods
A total of 62 cervical cancer patients were recruited during 1993-1994 and assigned into four groups treated with radiotherapy alone or radiotherapy combined with chemotherapy and/or thermotherapy. Ki67+ tumor cells, CD4+, CD8+, FoxP3+, OX40+ and granzyme B+ TILs were detected by immunohistochemistry. The viral load of HR-HPV in biopsy tissues before therapy was detected by in situ hybridization.

Results
The patients with high HPV viral load showed a significantly lower 15-year survival rate and an advanced International Federation of Gynecology and Obstetrics (FIGO) stage and increased recurrence rate. The distribution of Ki67+ tumor cells, FoxP3+ TILs, and CD8+/FoxP3+ ratio was obviously different between low and high HPV viral load groups. A worse clinical outcome was also implicated with increased HPV viral load tested by Cox regression analysis.

Conclusions
Patients with increased HR-HPV viral load tend to be resistant to therapy with decreased immune surveillance in the immune microenvironment. Thus, HR-HPV viral load would influence the local immune microenvironment, and then further affect the survival of cervical cancer patients.
A Note on Proposed Estimation Procedures for Claims-Based Frailty Indexes
Authors: R  Van Domelen Dane , Bandeen-Roche Karen 
Published: October 2019

Abstract
Two groups (Segal et al. Med Care. 2017;55(7):716–722; Segal et al. Am J Epidemiol. 2017;186(6):745–747; and Kim et al. J Gerontol A Biol Sci Med Sci. 2018;73(7):980–987) recently proposed methods for modeling frailty in studies where a reference standard frailty measure is not directly observed, but Medicare claims data are available. The groups use competing frailty measures, but the premise is similar: In a validation data set, model the frailty measure versus claims variables; in the primary data set, impute frailty status from claims variables, and conduct inference with those imputed values in place of the unobserved frailty measure. Potential use cases include risk prediction, confounding control, and prevalence estimation. In this commentary, we describe validity issues underlying these approaches, focusing mainly on risk prediction. Our main concern is that these approaches do not permit valid estimation of associations between the reference standard frailty measure (i.e., “frailty”) and health outcomes. We argue that Segal’s approach is akin to multiple imputation but with the outcome variable omitted from the imputation model, while Kim’s is akin to regression calibration but with many variables improperly treated as surrogates. We discuss alternatives for risk prediction, including a secondary approach previously considered by Kim et al., and briefly comment on other use cases.
Molecular fingerprint of female bovine embryos produced in vitro with high competence to establish and maintain pregnancy†
Authors: Zolini A M , Block J , Rabaglino M B , Tríbulo P , Hoelker M , Rincon G , Bromfield J J , Hansen P J 
Published: October 2019

Abstract
The objective was to identify the transcriptomic profile of in vitro-derived embryos with high competence to establish and maintain gestation. Embryos produced with X-sorted sperm were cultured from day 5 to day 7 in serum-free medium containing 10 ng/ml recombinant bovine colony-stimulating factor 2 (CSF2) or vehicle. The CSF2 was administered because this molecule can increase blastocyst competence for survival after embryo transfer. Blastocysts were harvested on day 7 of culture and manually bisected. One demi-embryo from a single blastocyst was transferred into a synchronized recipient and the other half was used for RNA-seq analysis. Using P &lt; 0.01 and a fold change &gt;2-fold or &lt;0.5 fold as cutoffs, there were 617 differentially expressed genes (DEG) between embryos that survived to day 30 of gestation vs those that did not, 470 DEG between embryos that survived to day 60 and those that did not, 432 DEG between embryos that maintained pregnancy from day 30 to day 60 vs those where pregnancy failed after day 30, and 635 DEG regulated by CSF2. Pathways and ontologies in which DEG were overrepresented included many related to cellular responses to stress and cell survival. It was concluded that gene expression in the blastocyst is different between embryos that are competent to establish and maintain pregnancy vs those that are not. The relationship between expression of genes related to cell stress and subsequent embryonic survival probably reflects cellular perturbations caused by embryonic development taking place in the artificial environment associated with cell culture.
Analysis of the uterine lumen in fertility-classified heifers: I. Glucose, prostaglandins, and lipids†
Authors: Moraes Joao G N , Behura Susanta K , Geary Thomas W , Spencer Thomas E 
Published: October 2019

AbstractSurvival and growth of the bovine conceptus (embryo and associated extraembryonic membranes) are dependent on endometrial secretions or histotroph found in the uterine lumen. Previously, serial embryo transfer was used to classify heifers as high fertile (HF), subfertile (SF), or infertile (IF). Here, we investigated specific histotroph components [glucose, prostaglandins (PGs), and lipids] in the uterine lumen of day 17 pregnant and open fertility-classified heifers. Concentrations of glucose in the uterine lumen were increased by pregnancy but did not differ among fertility-classified heifers. Differences in expression of genes encoding glucose transporters and involved with glycolysis and gluconeogenesis were observed between conceptuses collected from HF and SF heifers. In the uterine lumen, PGE2 and PGF2α were increased by pregnancy, and HF heifers had higher concentrations of PGE2, PGF2α, and 6-keto-PFG1α than SF heifers. Differences were found in expression of genes regulating PG signaling, arachidonic acid metabolism, and peroxisome proliferator-activated receptor signaling among conceptuses and endometrium from fertility-classified heifers. Lipidomics was conducted exclusively in samples from HF heifers, and phosphatidylcholine was the main lipid class that increased in the uterine lumen by pregnancy. Expression of several lipid metabolism genes differed between HF and SF conceptuses, and a number of fatty acids were differentially abundant in the uterine lumen of pregnant HF and SF heifers. These results support the ideas that uterine luminal histotroph impacts conceptus survival and programs its development and is a facet of dysregulated conceptus–endometrial interactions that result in loss of the conceptus in SF cattle during the implantation period of pregnancy establishment.
Ablation of conceptus PTGS2 expression does not alter early conceptus development and establishment of pregnancy in the pig†
Authors: Pfeiffer Caroline A , Meyer Ashley E , Brooks Kelsey E , Chen Paula R , Milano-Foster Jessica , Spate Lee D , Benne Joshua A , Cecil Raissa F , Samuel Melissa S , Ciernia Lauren A , Spinka Christine M , Smith Michael F , Wells Kevin D , Spencer Thomas E , Prather Randall S , Geisert Rodney D 
Published: October 2019

AbstractPig conceptuses secrete estrogens (E2), interleukin 1 beta 2 (IL1B2), and prostaglandins (PGs) during the period of rapid trophoblast elongation and establishment of pregnancy. Previous studies established that IL1B2 is essential for rapid conceptus elongation, whereas E2 is not essential for conceptus elongation or early maintenance of the corpora lutea. The objective of the present study was to determine if conceptus expression of prostaglandin-endoperoxide synthase 2 (PTGS2) and release of PG are important for early development and establishment of pregnancy. To understand the role of PTGS2 in conceptus elongation and pregnancy establishment, a loss-of-function study was conducted by editing PTGS2 using CRISPR/Cas9 technology. Wild-type (PTGS2+/+) and null (PTGS2−/−) fibroblast cells were used to create embryos through somatic cell nuclear transfer. Immunolocalization of PTGS2 and PG production was absent in cultured PTGS2−/− blastocysts on day 7. PTGS2+/+ and PTGS2−/− blastocysts were transferred into surrogate gilts, and the reproductive tracts were collected on either days 14, 17, or 35 of pregnancy. After flushing the uterus on days 14 and 17, filamentous conceptuses were cultured for 3 h to determine PG production. Conceptus release of total PG, prostaglandin F2⍺ (PGF2α), and PGE in culture media was lower with PTGS2−/− conceptuses compared to PTGS2+/+ conceptuses. However, the total PG, PGF2α, and PGE content in the uterine flushings was not different. PTGS2−/− conceptus surrogates allowed to continue pregnancy were maintained beyond 30 days of gestation. These results indicate that pig conceptus PTGS2 is not essential for early development and establishment of pregnancy in the pig.
Estrogen degrades Scribble in endometrial epithelial cells through E3 ubiquitin ligase HECW1 in the development of diffuse adenomyosis
Authors: Jin Zhixing , Liu Haiou , Xu Congjian 
Published: October 2019

Abstract
Despite its prevalence and the severity of symptoms, little is known about the pathogenesis and etiology of adenomyosis. In previous studies, the protein expression level of the polarity protein Scribble in the eutopic endometrium of patients with adenomyosis was found to be significantly decreased; however, little is known about its regulatory mechanism. In consideration of the important role of supraphysiologic estrogen production in the endometrium in the development of adenomyosis, we analyzed the effect and mechanism of estrogen on the expression of Scribble in vivo and in vitro. Firstly, we found Scribble was down-regulated in eutopic endometrium and negatively related with aromatase P450 in Tamoxifen-induced adenomyosis. Then, we established a 3D culture of primary endometrial epithelial cells and used found that estrogen could disrupt apical-basal polarity of endometrial glandular epithelial cells. Based on the following experiments and GEO datasets screening, we found estrogen regulates the expression level of Scribble by HECW1 through ubiquitination of Scribble protein. At last, we verified the expression of Scribble, HECW1 and aromatase P450 in eutopic endometrium of human and mouse specimens and found the expression of HECW1 and aromatase P450 was significantly increased, while the expression of Scribble was significantly downregulated. Furthermore, a positive correlation was found between HECW1 and aromatase P450, while a negative correlation was found between HECW1 and Scribble in human clinical tissue specimens. Therefore, our research may provide a new understanding of the pathogenesis of adenomyosis.
A positive feedback self-regulatory loop between miR-210 and HIF-1α mediated by CPEB2 is involved in trophoblast syncytiolization: implication of trophoblast malfunction in preeclampsia
Authors: Wang Hao , Zhao Yangyu , Luo Rongcan , Bian Xiaotao , Wang Yongqing , Shao Xuan , Li Yu-xia , Liu Ming , Wang Yan-Ling 
Published: October 2019

Abstract
The pregnancy complication preeclampsia is directly associated with hypoxic stress and insufficient trophoblast cell differentiation. The hypoxia-inducible microRNA (miRNA), miR-210, has been identified as a significantly up-regulated miRNA in preeclamptic placenta, and evidence in other cell types has indicated a feedback regulation between miR-210 and hypoxia-inducible factor-1α (HIF-1α) under hypoxic condition. It remains unclear whether and how the feedback loop between miR-210 and HIF-1α may contribute to trophoblast dysfunction in preeclampsia. Here we proved that cytoplasmic polyadenylation element-binding 2 (CPEB2) was a direct target of miR-210 in human trophoblast. CPEB2 could inhibit the translation of hypoxia-induced HIF-1α via directly binding the cytoplasmic polyadenylation element (CPE) site in the 3′-untranslated region (UTR) of HIF-1α mRNA. The increase in the HIF-1α level upon hypoxia treatment could be efficiently reversed by miR-210 inhibitor. In addition, CPEB2 was primarily expressed in villous syncytiotrophoblasts, and the suppression of trophoblast cell syncytialization by miR-210 could be significantly rescued by CPEB2 overexpression. In preeclamptic placenta, the expression of CPEB2 was evidently lower than normal pregnant control, and the miR-210 level was aberrantly higher and trophoblast syncytialization was limited. The findings revealed a positive feedback loop between miR-210 and HIF-1α that is mediated by CPEB2 in human trophoblasts, and demonstrated a mechanism underlying the insufficient trophoblast syncytialization in preeclampsia under hypoxic stress.
Analysis of the uterine lumen in fertility-classified heifers: II. Proteins and metabolites†
Authors: Moraes Joao G N , Behura Susanta K , Bishop Jeanette V , Hansen Thomas R , Geary Thomas W , Spencer Thomas E 
Published: October 2019

AbstractSurvival and growth of the bovine conceptus is dependent on endometrial secretions or histotroph. Previously, serial blastocyst transfer was used to classify heifers as high fertile (HF), subfertile (SF), or infertile (IF). Here, we investigated specific histotroph components (proteins and metabolites) in the uterine lumen of day 17 fertility-classified heifers. Interferon tau (IFNT) was more abundant in uterine lumenal fluid (ULF) of pregnant HF than SF animals as the conceptus was longer in HF heifers. However, no differences in endometrial expression of selected classical and nonclassical interferon-stimulated genes (ISGs) were observed, suggesting that IFNT signaling in the endometrium of pregnant HF and SF heifers was similar. Pregnancy significantly increased the abundance of several proteins in ULF. Based on functional annotation, the abundance of a number of proteins involved in energy metabolism, oxidative stress, amino acid metabolism, and cell proliferation and differentiation were greater in the ULF of pregnant HF than SF heifers. Metabolomics analysis found that pregnancy only changed the metabolome composition of ULF from HF heifers. The majority of the metabolites that increased in the ULF of pregnant HF as compared to SF heifers were associated with energy and amino acid metabolism. The observed differences in ULF proteome and metabolome are hypothesized to influence uterine receptivity with consequences on conceptus development and survival in fertility-classified heifers.
Imaging markers of disability in aquaporin-4 immunoglobulin G seropositive neuromyelitis optica: a graph theory study
Authors: Chien Claudia , Oertel Frederike Cosima , Siebert Nadja , Zimmermann Hanna , Asseyer Susanna , Kuchling Joseph , Scheel Michael , Ruprecht Klemens , Bellmann-Strobl Judith , Paul Friedemann , Brandt Alexander U 
Published: October 2019

Abstract
Neuromyelitis optica spectrum disorders lack imaging biomarkers associated with disease course and supporting prognosis. This complex and heterogeneous set of disorders affects many regions of the central nervous system, including the spinal cord and visual pathway. Here, we use graph theory-based multimodal network analysis to investigate hypothesis-free mixed networks and associations between clinical disease with neuroimaging markers in 40 aquaporin-4-immunoglobulin G antibody seropositive patients (age = 48.16 ± 14.3 years, female:male = 36:4) and 31 healthy controls (age = 45.92 ± 13.3 years, female:male = 24:7). Magnetic resonance imaging measures included total brain and deep grey matter volumes, cortical thickness and spinal cord atrophy. Optical coherence tomography measures of the retina and clinical measures comprised of clinical attack types and expanded disability status scale were also utilized. For multimodal network analysis, all measures were introduced as nodes and tested for directed connectivity from clinical attack types and disease duration to systematic imaging and clinical disability measures. Analysis of variance, with group interactions, gave weights and significance for each nodal association (hyperedges). Connectivity matrices from 80% and 95% F-distribution networks were analyzed and revealed the number of combined attack types and disease duration as the most connected nodes, directly affecting changes in several regions of the central nervous system. Subsequent multivariable regression models, including interaction effects with clinical parameters, identified associations between decreased nucleus accumbens (β = −0.85, P = 0.021) and caudate nucleus (β = −0.61, P = 0.011) volumes with higher combined attack type count and longer disease duration, respectively. We also confirmed previously reported associations between spinal cord atrophy with increased number of clinical myelitis attacks. Age was the most important factor associated with normalized brain volume, pallidum volume, cortical thickness and the expanded disability status scale score. The identified imaging biomarker candidates warrant further investigation in larger-scale studies. Graph theory-based multimodal networks allow for connectivity and interaction analysis, where this method may be applied in other complex heterogeneous disease investigations with different outcome measures.
Charting the Path Forward: Development, Goals and Initiatives of the 2019 Infectious Diseases Society of America Strategic Plan
Authors: Sears Cynthia L , File Thomas M , Alexander Barbara D , McQuillen Daniel P , MacIntyre Ann T , Allen Upton D , Colasanti Jonathan A , Siddiqui Javeed , Reveles Kelly R , Busky Chris ,   Infectious Diseases Society of America (IDSA) Board of Directors
Published: October 2019

Abstract
In October 2018, the Infectious Diseases Society of America (IDSA) Board of Directors (BOD) decided to develop a 2019 IDSA Strategic Plan. The IDSA BOD has invested in strategic planning at regular intervals as part of an ongoing process to review and to renew the vision and direction of IDSA. Herein, the 2018–2019 strategic planning process and outcomes are described. The 2019 IDSA Strategic Plan presents 4 key initiatives: (1) optimize the development, dissemination, and adoption of timely and relevant ID guidance and guidelines that improve the outcomes of clinical care; (2) quantify, communicate, and advocate for the value of ID physicians to increase professional fulfillment and compensation; (3) facilitate the growth and development of the ID workforce to meet emerging scientific, clinical, and leadership needs; and (4) develop and position a new tool to serve as the leading US benchmark to measure and drive national progress on antimicrobial resistance. The BOD looks forward to developing, implementing, assessing, and advancing the 2019 IDSA Strategic Plan working with member volunteers, Society partners, and IDSA staff.
The risk of venous thromboembolism after surgery for esophagogastric malignancy and the impact of chemotherapy: a population-based cohort study
Authors: Adiamah Alfred , Ban Lu , West Joe , Humes David J 
Published: October 2019

SUMMARY
To define the incidence of postoperative venous thromboembolism (VTE) and effects of chemotherapy in a population undergoing surgery for esophagogastric cancer. This population-based cohort study used linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care data from England to identify subjects undergoing esophageal or gastric cancer surgery between 1997 and 2014. Exposures included age, comorbidity, smoking, body mass index, and chemotherapy. Crude rates and adjusted hazard ratios (HRs) were calculated for rate of first postoperative VTE using Cox regression models. The cumulative incidence of VTE at 1 and 6 months was estimated accounting for the competing risk of death from any cause. Of the 2,452 patients identified, 1,012 underwent gastrectomy (41.3%) and 1,440 esophagectomy (58.7%). Risk of VTE was highest in the first month, with absolute VTE rates of 114 per 1,000 person-years (95% CI 59.32–219.10) following gastrectomy and 172.73 per 1,000 person-years (95% CI 111.44–267.74) following esophagectomy. Neoadjuvant and adjuvant chemotherapy was associated with a six-fold increased risk of VTE following gastrectomy, HR 6.19 (95% CI 2.49–15.38). Cumulative incidence estimates of VTE at 6 months following gastrectomy in patients receiving no chemotherapy was 1.90% and esophagectomy 2.21%. However, in those receiving both neoadjuvant and adjuvant chemotherapy, cumulative incidence following gastrectomy was 10.47% and esophagectomy, 3.9%. VTE rates are especially high in the first month following surgery for esophageal and gastric cancer. The cumulative incidence of VTE at 6 months is highest in patients treated with chemotherapy. In this category of patients, targeted VTE prophylaxis may prove beneficial during chemotherapy treatment.
A Natural High-Sugar Diet Has Different Effects on the Prokaryotic Community Structures of Lower and Higher Termites (Blattaria)
Authors: Zeng Wenhui , Liu Bingrong , Zhong Junhong , Li Qiujian , Li Zhiqiang 
Published: October 2019

Abstract
The lignocellulosic digestive symbiosis in termites is a dynamic survival adaptation system. While the contribution of hereditary and habitat factors to the development of the symbiotic bacterial community of termites had been confirmed, the manner in which these factors affect functional synergism among different bacterial lineages has still not been fully elucidated. Therefore, the 16S rRNA gene libraries of Odontotermes formosanus Shiraki (Blattodea: Termitidae) and Coptotermes formosanus Shiraki (Blattodea: Rhinotermitidae) sampled from sugarcane fields (high sugar) or pine tree forests (no free sugar) were sequenced. The results verify that the prokaryotic community structures of termites could be significantly reshaped by native dietary isolation within a species. Although the most dominant phyla are convergent in all samples, their relative abundances in these two termite species exhibited a reverse variation pattern when the termite hosts were fed on the high-sugar diet. Furthermore, we showed that the taxonomic composition of the dominant phyla at the family or genus level differentiate depending on the diet and the host phylogeny. We hypothesize that the flexible bacterial assemblages at low taxonomic level might exert variable functional collaboration to accommodate to high-sugar diet. In addition, the functional predictions of Tax4Fun suggest a stable metabolic functional structure of the microbial communities of the termites in both different diet habitats and taxonomy. We propose that the symbiotic bacterial community in different host termites developed a different functional synergistic pattern, which may be essential to maintain the stability of the overall metabolic function for the survival of termites.