bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I Study of the Bifunctional Fusion Protein Bintrafusp Alfa in Asian Patients with Advanced Solid Tumors, Including a Hepatocellular Carcinoma Safety-Assessment Cohort
Authors: Doi Toshihiko , Fujiwara Yutaka , Koyama Takafumi , Ikeda Masafumi , Helwig Christoph , Watanabe Morihiro , Vugmeyster Yulia , Kudo Masatoshi 
Published: April 2020

Abstract

Lessons Learned
Bintrafusp alfa had a manageable safety profile and demonstrated preliminary clinical activity in heavily pretreated patients with solid tumors (including hepatocellular carcinoma) with no or limited treatment options. Findings from this study suggest bintrafusp alfa may be a novel therapeutic approach for patients with advanced solid tumors. Additional trials are needed to further explore safety and efficacy of bintrafusp alfa in specific tumor types.

Background
Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of transforming growth factor-β (TGF-β) RII receptor (a TGF-β “trap”) fused to a human immunoglobulin (Ig) G1 antibody blocking programmed death-ligand 1 (PD-L1). Bintrafusp alfa is designed to neutralize TGF-β signaling by “trapping” and sequestering all TGF-β isoforms, and this trap function is physically linked to PD-L1 blockade in the tumor microenvironment.

Methods
NCT02699515 was a phase I, open-label, dose-escalation study of bintrafusp alfa (3, 10, and 20 mg/kg every 2 weeks) in Asian patients with advanced solid tumors, including a hepatocellular carcinoma (HCC) safety-assessment cohort. The primary objective was safety and tolerability; the secondary objective is best overall response.

Results
As of August 24, 2018, 23 patients (including 9 in the HCC cohort) received bintrafusp alfa. Eight patients experienced treatment-related adverse events (TRAEs). Three patients had grade 3 TRAEs (13.0%; hypoacusis, hyponatremia, hypopituitarism, increased blood creatine phosphokinase, and intracranial tumor hemorrhage); one had grade 4 hyponatremia (4.3%). No treatment-related deaths occurred. In the dose-escalation cohort, two patients had a confirmed partial response, and 3 had stable disease (SD), for an overall response rate of 14.3% and a disease control rate (DCR) of 35.7%. In the HCC cohort, one patient had SD (DCR, 11.1%). A dose-proportional pharmacokinetics profile was observed at doses of &gt;3 mg/kg.

Conclusion
Bintrafusp alfa had a manageable safety profile and preliminary efficacy in heavily pretreated patients with advanced solid tumors, including HCC.
Papular atrichia
Authors: Lunge Snehal B. , Vyshak B. M. 
Published: April 2020

<p>Congenital atrichia or papular atrichia is a rare form of irreversible alopecia inherited autosomal recessively. Atrichia congenita with papular lesions represents a complex and heterogeneous group of genodermatoses characterized by irreversible complete hair loss soon after birth, and associated with the development of keratin-filled cysts over the body. Mutation of the human hairless (HR) gene on chromosome 8p22 has been implicated with this condition. It has broad differential diagnosis and poses diagnostic and therapeutic challenges. We report an 8 year girl presenting with complete loss of hair over scalp, eye brows, eye lashes, and body soon after birth with papular lesions over face.<strong></strong></p>
A study on the presenting features observed in 100 patients of atopic dermatitis in a tertiary care hospital in North-Eastern India
Authors: Gupta Bhaskar , Lochav Bhawna 
Published: April 2020

Atopic dermatitis is a relatively common age-related disease. Its pathophysiology is majorly insubstantial. Also, it appears as a result of interplay of maternal and inheritance, intrauterine and environmental factors. Also, immune dysregulation has an important role.To study the presenting features of atopic dermatitis.100 patients of atopic dermatitis which were diagnosed on the basis of modified UK working party criteria, after which clinical presentations were noted in a preset proforma.78% were in the age group of 2-12 years, of which 65% were males and 35% were females.Atopic dermatitis is a distinct, overt, age and IgE-related entity frequently showing different demographic and clinical presentations.
MiR-34c Downregulation Leads to SOX4 Overexpression and Cisplatin Resistance in Nasopharyngeal Carcinoma
Authors: Bissey Pierre-Antoine , Teng Mona , Law Jacqueline H , Shi Wei , Bruce Jeff P , Petit Valentin , Sai Tsao W , Yip Kenneth W , Liu Fei-Fei 
Published: April 2020

Abstract
Background : A major cause of disease-related death in nasopharyngeal carcinoma (NPC) is the development of distant metastasis (DM) despite combination chemoradiotherapy treatment. We previously identified and validated a four microRNA (miRNA) signature that is prognostic for DM. In this study, characterization of a key component of this signature, miR-34c, revealed its role in chemotherapy resistance. Methods: 246 NPC patient biopsy samples were subject to comprehensive miRNA profiling and immunohistochemistry (IHC). Two human normal nasopharyngeal cell lines (immortalized; NP69 and NP460), as well as the NPC cell line C666-1, were used to generate pre-miR-34c (gain-of-function) and anti-miR-34c (loss-of-function) cells. Signaling pathways were assessed using quantitative real-time PCR (qRT-PCR) and Western blot. Cell viability was measured using the ATPlite assay. Results: MiR-34c was downregulated in NPC patient samples, and confirmed in vitro to directly target SOX4, a master regulator of epithelial-to-mesenchymal transition (EMT). MiR-34c downregulation triggered EMT-representative changes in NP69 and NP460 whereby Snail, ZEB1, CDH2, and SOX2 were upregulated, while Claudin-1 and CDH1 were downregulated. Phenotypically, inhibition of miR-34c led to cisplatin resistance, whereas miR-34c over-expression sensitized NPC cells to cisplatin. TGFβ1 decreased miR-34c and increased SOX4 expression in vitro . The TGFβ receptor 1 inhibitor SB431542 reduced SOX4 expression and increased cisplatin sensitivity. Finally, IHC revealed that lower SOX4 expression was associated with improved overall survival in chemotherapy-treated NPC patients. Conclusion: miR-34c downregulation correlates with higher incidence of DM. Repression of miR-34c was shown to increase SOX4 expression, which leads to cisplatin resistance, while TGFβ1 was found to repress miR-34c expression. Taken together, our study demonstrates that inhibition of the TGFβ1 pathway could be a strategy to restore cisplatin sensitivity in NPC.
Health-related quality of life (FACT-GP) in Sweden
Authors: Bagge Ann-Sophie Lindqvist , Carlander Anders , Fahlke Claudia , Bagge Roger Olofsson 
Published: April 2020

Abstract
Background: Many studies have used disease-specific instruments, such as the Functional Assessment of Cancer Therapy (FACT), when studying health-related quality of life (HRQOL) in patients. Few studies however, have described normative HRQOL values in the general population using FACT - General Population (FACT-GP) . The general aim of the present study is thus to describe the normative HRQOL values in the general Swedish population by using the FACT-GP instrument and to investigate to what degree sociodemographic factors and status of self-rated health (SRH) correlate with HRQOL. Methods: The participants consisted of a pre-stratified (gender, age and education) sample of Swedish citizens that previously had enrolled to be a part of a web panel hosted by a research institute (SOM Institute) at the University of Gothenburg in Sweden. The HRQOL was assessed by using the FACT-GP and SRH. Results: A higher FACT-GP score was mainly associated with males, higher age, higher income and better SRH. The results showed that the Swedish sample scored lower on FACT-GP than previous studies. Conclusions: Since HRQOL is frequently used as an important endpoint in healthcare research, there is an increasing need for normative data. The results from this study serve as a general population standard against which other studied HRQOL-data could be evaluated.
Serum Lipids Profiling Perturbances in Patients with Ischemic Heart Disease and Ischemic Cardiomyopathy
Authors: Yang Lin , Wang Liang , Deng Yangyang , Sun Lizhe , Low Bowen , Yuan Zuyi , Wu Yue , Zhou Bo , Liu Junhui , She Jianqing 
Published: April 2020

Abstract
Background: Ischemic heart disease (IHD) is a common cardiovascular disorder associated with inadequate blood supply to the myocardium. Chronic coronary ischemia leads to ischemic cardiomyopathy (ICM). Despite their rising prevalence and morbidity, few studies have discussed the lipids alterations in these patients. Methods: In this cross-sectional study, we analyzed serum lipids profile in IHD and ICM patients using a lipidomics approach. Consecutive consenting patients admitted to the hospital for IHD and ICM were enrolled. Serum samples were obtained after overnight fasting. Non-targeted metabolomics was applied to demonstrate lipids metabolic profile in control, IHD and ICM patients. Results: A total of 63 and 62 lipids were detected in negative and positive ion mode respectively. Among them, 16:0 Lyso PI, 18:1 Lyso PI in negative ion mode, and 19:0 Lyso PC, 12:0 SM d18:1/12:0, 15:0 Lyso PC, 17:0 PC, 18:1-18:0 PC in positive ion mode were significantly altered both in IHD and ICM as compared to control. 13:0 Lyso PI, 18:0 Lyso PI, 16:0 PE, 14:0 PC DMPC, 16:0 ceramide, 18:0 ceramide in negative ion mode, and 17:0 PE, 19:0 PC, 14:0 Lyso PC, 20:0 Lyso PC, 18:0 PC DSPC, 18:0-22:6 PC in positive ion mode were significantly altered only in ICM as compared to IHD and control. Conclusion: Using non-targeted lipidomics profiling, we have successfully identified a group of circulating lipids that were significantly altered in IHD and ICM. The lipids metabolic signatures shed light on potential new biomarkers and therapeutics for preventing and treating ICM.
Oral Status of elderly patients in long stay centres: A systematic review
Authors: Ruiz-Roca Juan Antonio , Martin-Fuentes Dora , Martinez-Beneyto Yolanda , Oñate-Sanchez Ricardo Elias 
Published: April 2020

Abstract
Background: Elderly patients who spend long periods hospitalized or those who are in a situation of institutionalization represent a risk group in this regard, as many of them suffer a degree of dependence and need help to perform the basic tasks of personal care. It is therefore important to learn more of the oral health status of this group of patients in order to make a proper assessment of the situation and to develop protocols for its management. The purpose of the study was to conduct a systematic review to ascertain the oral health status of elderly patients admitted to institutions or hospitalized for a long period of time.Methods: a systematic review of the literature published in two different databases (PubMed, Embase and Cochrane Library) was carried out, with 12 different combinations of keywords based on the following selection criteria: studies published in the last 5 years, in English and/or Spanish and/or Portuguese, with samples of ≥30 patients, performed in patients older than 65 years, admitted to any type of institution and/or hospital center for at least 7 days and in which the state of hard and/or soft tissues of the oral cavity were evaluated in some way. The selected articles were subjected to a thorough analysis.Results: The search strategy covered 1,014 articles: 689 from Pubmed and 325 from Cochrane Library. After applying the eligibility criteria, five articles were selected for our review. The level of evidence of the articles was3, a sample of 773 patients most of them were women with an average age older than 70 years old.Conclusions: the oral health of patients aged more than 65 is worse than that of the rest population. Long hospital stays or being institutionalized in a residence makes this group susceptible to a worsening of their oral health status. It is necessary to develop protocols for the oral health care of these patients, accompanied by training programs for the personnel responsible.
Differences among families in craniofacial shape at early life-stages of Arctic charr (Salvelinus alpinus)
Authors: Beck Samantha Victoria , Räsänen Katja , Leblanc Camille A. , Skúlason Skúli , Jónsson Zophonías O. , Kristjánsson Bjarni K. 
Published: April 2020

Abstract
Background
Organismal fitness can be determined at early life-stages, but phenotypic variation at these early life-stages has rarely been considered in studies on evolutionary diversification. The trophic apparatus has been shown to contribute to sympatric resource-mediated divergence in several taxa. However, processes underlying this diversification are poorly understood. Using a phenotypically variable morph of Icelandic Arctic charr (Salvelinus alpinus), we reared offspring from multiple families under standardized laboratory conditions and tested to what extent family (i.e. direct genetic and maternal effects) contributes to offspring morphology at hatching (H) and first feeding (FF). To understand the underlying mechanisms behind early life-stage variation in morphology, we examined how craniofacial shape varied according to family, egg size, offspring size and individual candidate genes related to craniofacial development. Finally, we assessed whether craniofacial shape and expression of genes related to craniofacial development covaried.
Results
We found effects of family for offspring craniofacial shape at both H and FF, whilst relative expression levels of Sgk1 (a gene involved in craniofacial shape divergence) correlated with craniofacial shape at FF. However, there were no evidence to suggest that mean egg size or individual offspring size influenced offspring morphology.
Conclusions
This study provides evidence for within population family effects for phenotypic variation in trophic morphology, indicating the potential for genetic and/or maternal effects to facilitate resource polymorphism.
Variability of the Edinburgh Postnatal Depression Scale for Antenatal Depression Screening in Spanish: a Cross-Sectional Study.
Authors: Manso-Martínez María Esperanza , Esteban-Gonzalo Laura , Marazuela-López Beatriz , García-Luengo Alfonso , de-la-Torre-Gallego Arantzazu , González-Pascual Juan Luis 
Published: April 2020

Abstract
Background Depression during pregnancy is a prevalent problem with significant potential health effects on women and children. The most widely used screening instrument is the Edinburgh Postnatal Depression Scale (EPDS). Two validations of the EDPS in Spanish have been published. Given the differences in cut-off point, sensibility and specificity among the Spanish EPDS validations, the aim of this study is to provide further information regarding the topic through a validation of the EPDS is Spain with a different sample.Methods Cross-sectional study. 194 women being followed up for normal pregnancy in Primary Healthcare in Spain completed the EPDS and had a semi-structured interview with a clinical psychologist using the DSM-5 manual criteria for diagnosing depression. The ROC curve was calculated to determine the optimal cut-off point, sensitivity and specificity.Results The age range of the participating pregnant women was from 18 to 42 years of age. The optimal cut-off point is 11/12, with a sensitivity of 93.33% and a specificity of 91.62%. The ROC curve has an area of 0.936. Discussion The cut-off point is slightly lower than that of the Spanish version validated in Chile. Likewise, compared to the version validated in Spain, the cut-off point is slightly higher. In our research, sensitivity is notably higher, and specificity slightly lower than in the Spanish version validated in Chile. Compared with the Spanish version validated in Spain, sensibility and specificity were notably higher in our research.Conclusions Given the differences in cut-off point, sensibility and specificity, we propose to continue searching for an optimal cut-off point in the Spanish version of the EPDS. In our opinion, further research is necessary in order to use the EPDS for antenatal depression screening in Spain. A multicentric study including pregnant women from all over the country would be suitable.
Endoscopic severe mucosal atrophy indicates the presence of gastric cancer after Helicobacter pylori eradication
Authors: Ohno Akiko , Miyoshi Jun , Kato Atsushi , Miyamoto Naohiko , Yatagai Takahito , Hada Yu , Kusuhara Mitsunori , Jimbo Yoko , Ida Yosuke , Tokunaga Kengo , Okamoto Susumu , Hisamatsu Tadakazu 
Published: April 2020

Abstract
Background
Gastric cancer after Helicobacter pylori (HP) eradication is a crucial clinical challenge today as HP eradication therapy is widely performed. Detecting gastric cancer after HP eradication tends to be difficult with normal white-light endoscopy. In the present study, we aimed to identify easily-evaluated endoscopic findings that indicate the presence of gastric cancer after HP eradication so that endoscopists can consider additional detailed examinations at the site.
Methods
We analyzed the endoscopic images of 43 patients who underwent endoscopic submucosal dissection for early gastric cancer after HP eradication and 119 patients with an HP eradication history who underwent esophagogastroduodenoscopy for a medical checkup. Endoscopic findings were evaluated according to the Kyoto classification of gastritis (atrophy, intestinal metaplasia, enlarged folds, nodularity, and diffuse redness) and map-like redness.
Results
Patients with gastric cancer had significantly higher total Kyoto risk scores; more atrophy, intestinal metaplasia, and diffuse redness; and a significantly higher prevalence of map-like redness compared with those without gastric cancer, in the univariate analyses. We used logistic regression analysis with forward selection based on the likelihood ratio to develop a model using atrophy and diffuse redness. Receiver operating characteristic analysis showed that a score of A2 in the Kyoto classification of gastritis (open-type atrophic pattern in the Kimura–Takemoto classification) was an endoscopic marker for the presence of post-HP-eradication gastric cancer.
Conclusions
Endoscopic severe gastric mucosal atrophy is useful to screen patients for gastric cancer after HP eradication.
LDHs enhanced the immune response of animals to foot-and-mouth disease virus
Authors: Wu Peng , Zhang Yunfeng , Yin Xinyue , He Yanhua , Zhang Qian , Chen Chuangfu 
Published: April 2020

Abstract
Background: Foot-and-mouth disease (FMD) is a highly transmissible disease that leads to vast economic losses in many countries. Prevention using inactivated vaccines is one effective measure used to control FMD. Unfortunately, inactivated FMD vaccines provide only short-term protection and require a cold-chain system. In recent years, many studies have shown that layered double metal hydroxides (LDHs) carrying antigens can be used to strongly induce immune responses. In this study, LDH nanoparticles (NPs) were prepared by hydrothermal synthesis. LDH particle size, electric potential, and morphology were measured and observed. The adsorption capacity of LDH NPs to FMDV was tested. The effects of LDH as an adjuvant on inactivated FMDV vaccines were further evaluated and compared with commercial FMDV ISA-206 in BALB/C female mice and Yorkshire pigs.Results: LDH NPs were successfully prepared with a uniform particle size of ~87.21 nm, regular edges, a loose hexagonal shape and positive zeta charge of 32 mV. The maximum absorption concentration was 0.16-0.31 µg FMDV/µg LDH. In the mouse experiment, antibody of immunized with LDH + FMDV were induced significantly higher from days 42-98 compared to saline + FMDV (P<0.01) and significantly higher compared to ISA-206+FMDV on day 56 post-immunization (P<0.05). After day14 post-immunization, IFN-γ content was significantly increased (P<0.05). In the pig experiment, antibody levels in both the ISA-206 + FMDV and LDH + FMDV were positive and were significantly higher compared with the PBS group on day 7 (P<0.005). Antibody levels in 90% pigs were positive on day 56 in the LDH group. The neutralizing antibody levels in the LDH and ISA-206 groups were significantly higher from days 7-28 compared to the PBS control group (P<0.05). Thus, LDH NPs were effective at inducing an immune response against FMDV.Conclusions: LDHs with a loose hexagonal shape and a positive charge were prepared. LDHs can effectively induce humoral- and cell-mediated immune responses in mice and pigs. In addition, the LDHs had a slow-release effect and produced antibodies continuously. LDHs may act as an excellent FMDV adjuvant.
Sarcopenia as a Novel Prognostic Factor in the Patients of Primary Localized Gastrointestinal Stromal Tumor
Authors: Song He , Dong Ming 
Published: April 2020

Abstract
BackgroundSarcopenia predicts poor prognosis of a variety of gastrointestinal malignancies. However, there is a lack of study on the association between skeletal muscle index (SMI) and the prognosis of gastrointestinal stromal tumor (GIST). The aim of this study is to develop a novel nomogram based on sarcopenia for GIST patients to predict overall survival (OS)MethodsSMI was measured by computed tomography scan of 107 patients who underwent resection for primary localized gastrointestinal stromal tumor (GIST). Sarcopenia was defined by cutoff values for SMI as 40.1 cm 2 /m 2 and 39.8 cm 2 /m 2 using optimum stratification for males and females respectively. Factors were included in the nomogram were specified by univariate and multiple Cox proportional hazard analysis. Concordance index (C-index) and calibration curves were conducted to measure the discrimination and accuracy of the nomogram. The utility of the nomogram was assessed by the decision curve analysis (DCA).ResultsTwenty-eight (26.2%) of 107 patients were sarcopenic. Sarcopenia was correlated significantly with BMI, albumin, female sex, resection style, mitotic index, rupture status, survival. Sarcopenia was significantly related to decreased overall survival (p = 0.003).The nomogram including sarcopenia status, resection style and mitotic index had an excellent discrimination with C-index 0.794. The calibration curves represented a good accordance between the actual observation and nomogram prediction for overall survival. Decision curve analysis illustrated that the nomogram was helpful in clinic .ConclusionsWe developed a nomogram based on sarcopenia to predict overall survival after resection of GISTs which is an effective and favorable prognostication tool.