bluuebunny/crossref_metadata_2025_split huggingface dataset:
Participation of the ATR/CHK1 pathway in replicative stress targeted therapy of high-grade ovarian cancer
Authors: Gralewska Patrycja , Gajek Arkadiusz , Marczak Agnieszka , Rogalska Aneta 
Published: April 2020

AbstractOvarian cancer is one of the most lethal gynecologic malignancies reported throughout the world. The initial, standard-of-care, adjuvant chemotherapy in epithelial ovarian cancer is usually a platinum drug, such as cisplatin or carboplatin, combined with a taxane. However, despite surgical removal of the tumor and initial high response rates to first-line chemotherapy, around 80% of women will develop cancer recurrence. Effective strategies, including chemotherapy and new research models, are necessary to improve the prognosis. The replication stress response (RSR) is characteristic of the development of tumors, including ovarian cancer. Hence, RSR pathway and DNA repair proteins have emerged as a new area for anticancer drug development. Although clinical trials have shown poly (ADP-ribose) polymerase inhibitors (PARPi) response rates of around 40% in women who carry a mutation in the BRCA1/2 genes, PARPi is responsible for tumor suppression, but not for complete tumor regression. Recent reports suggest that cells with impaired homologous recombination (HR) activities due to mutations in TP53 gene or specific DNA repair proteins are specifically sensitive to ataxia telangiectasia and Rad3-related protein (ATR) inhibitors. Replication stress activates DNA repair checkpoint proteins (ATR, CHK1), which prevent further DNA damage. This review describes the use of DNA repair checkpoint inhibitors as single agents and strategies combining these inhibitors with DNA-damaging compounds for ovarian cancer therapy, as well as the new platforms used for optimizing ovarian cancer therapy.
Rare homozygous mutation in TUBB8 associated with oocyte maturation defect-2 in a consanguineous mating family
Authors: Xing Qiong , Wang Ruyi , Chen Beili , Li Lin , Pan Hong , Li Tengyan , Ma Xu , Cao Yunxia , Wang Binbin 
Published: April 2020

Abstract
Purpose
Variations in many genes may lead to the occurrence of oocyte maturation defects. To investigate the genetic basis of oocyte maturation defects, we performed clinical and genetic analysis of a pedigree.

Methods
The proband with oocyte maturation defect-2 receiving ovulation induction therapy and her parents were selected for clinical detection, whole exome sequencing and Sanger sequencing. One unrelated healthy woman received ovulation induction therapy as control. Mutations were assessed after frequency screening of public exome databases. Then homozygous variants shared by the proband and her parents were selected.

Results
Arrest of oocytes maturation was observed. A new missense mutation in TUBB8 (TUBB8: NM_177,987: exon 2: c. C161T: p. A54V) was identified, which was shown to be rare compared with public databases. The variant was highly conserved among primates, and was suggested to be deleterious by online software prediction.

Conclusions
The homozygote of this variant (TUBB8: NM_ 177,987: exon 2:c.C161T: p.A54V) might affect spindle assembly, cause arrest of oocyte maturation and lead to oocyte maturation defect-2.
Biological control of Aedes mosquito larvae with carnivorous aquatic plant, Utricularia macrorhiza
Authors: Couret Jannelle , Notarangelo Marco , Veera Sarashwathy , LeClaire-Conway Noah , Ginsberg Howard S. , LeBrun Roger L. 
Published: April 2020

Abstract
Background
Biological controls with predators of larval mosquito vectors have historically focused almost exclusively on insectivorous animals, with few studies examining predatory plants as potential larvacidal agents. In this study, we experimentally evaluate a generalist plant predator of North America, Utricularia macrorhiza, the common bladderwort, and evaluate its larvacidal efficiency for the mosquito vectors Aedes aegypti and Aedes albopictus in no-choice, laboratory experiments. We sought to determine first, whether U. macrorhiza is a competent predator of container-breeding mosquitoes, and secondly, its predation efficiency for early and late instar larvae of each mosquito species.

Methods
Newly hatched, first-instar Ae. albopictus and Ae. aegypti larvae were separately exposed in cohorts of 10 to field-collected U. macrorhiza cuttings. Data on development time and larval survival were collected on a daily basis to ascertain the effectiveness of U. macrorhiza as a larval predator. Survival models were used to assess differences in larval survival between cohorts that were exposed to U. macrorhiza and those that were not. A permutation analysis was used to investigate whether storing U. macrorhiza in laboratory conditions for extended periods of time (1 month vs 6 months) affected its predation efficiency.

Results
Our results indicated a 100% and 95% reduction of survival of Ae. aegypti and Ae. albopictus larvae, respectively, in the presence of U. macrorhiza relative to controls within five days, with peak larvacidal efficiency in plant cuttings from ponds collected in August. Utricularia macrorhiza cuttings, which were prey-deprived, and maintained in laboratory conditions for 6 months were more effective larval predators than cuttings, which were maintained prey-free for 1 month.

Conclusions
Due to the combination of high predation efficiency and the unique biological feature of facultative predation, we suggest that U. macrorhiza warrants further development as a method for larval mosquito control.
A unique thymus-derived regulatory T cell subset associated with systemic lupus erythematosus
Authors: Hanaoka Hironari , Nishimoto Tetsuya , Okazaki Yuka , Takeuchi Tsutomu , Kuwana Masataka 
Published: April 2020

Abstract
Background
Foxp3 is a marker for regulatory T cells (Treg cells), but recent studies have shown the plasticity and heterogeneity of CD4+Foxp3+ T cells. This study aimed to examine the phenotype and function of circulating CD4+Foxp3+ T cells in patients with systemic lupus erythematosus (SLE).

Methods
We enrolled 47 patients with SLE, 31 with organ-specific autoimmune diseases (15 with multiple sclerosis and 16 with primary immune thrombocytopenia), and 19 healthy subjects. Peripheral blood mononuclear cells were used to evaluate the proportion and phenotype of CD4+Foxp3+ cells using multicolor flow cytometry, the status of the Treg-specific demethylated region (TSDR) of the foxp3 gene by methylation-specific polymerase chain reaction, and the immunoregulatory function of CD4+CD25+ cells by allogeneic mixed lymphocyte reaction. Immunohistochemistry of renal biopsy specimens obtained from 6 patients with lupus nephritis and 5 with IgA nephropathy was conducted to detect IL-17A-expressing CD4+Foxp3+ cells.

Results
CD4+Foxp3+ T cells were increased in SLE patients compared with organ-specific autoimmune disease controls or healthy controls. Circulating CD4+Foxp3+ T cells were correlated with the disease activity of SLE. The increased CD4+Foxp3+ T cells in active SLE patients were mainly derived from thymus-derived Treg (tTreg) cells, as determined by a demethylated TSDR status, and represented a unique phenotype, upregulated expression of CD49d, CD161, and IL-17A, with immunosuppressive ability comparable to that of healthy controls. Finally, CD4+Foxp3+IL-17A+ cells were infiltrated into the renal biopsy specimens of patients with active lupus nephritis.

Conclusions
A unique tTreg subset with dichotomic immunoregulatory and T helper 17 phenotypes is increased in the circulation of SLE patients and may be involved in the pathogenic process of SLE.
The effectiveness of a longitudinal ultrasound curriculum for general pediatricians working in a Puerto Rican emergency department: a pilot study
Authors: Sepulveda-Ortiz Veronica , Warkentine Fred , Starr-Seal Rebecca , Rominger Anna 
Published: April 2020

Abstract
Background
The Hospital Pediatrico Universitario (HOPU) is the principal institution in Puerto Rico offering medical services to the children of the island and the Caribbean. There is limited use of point-of-care ultrasound (PoCUS) in their emergency department (ED) and obtaining an ultrasound through radiology is prohibitively time consuming. The objective of this study is to increase PoCUS knowledge and comfort by the ED physicians in the HOPU pediatric emergency department.

Results
Thirteen general pediatricians completed the entire PoCUS course, but only 10 completed both the pre- and post-tests and therefore included in the analysis (N = 10). Pretest scores ranged from 30 to 63.3% with a mean of 41.6% [standard deviation (SD) 9.95]. The posttest scores ranged from 55 to 96%, with a mean of 66.1% (SD 12.26). The mean difference in scores was 24.42% (95% confidence interval 17.9, 30.9) with a significance of p < 0.05 and range of 8.3–36.6%. Physician experience and confidence with each topic improved from baseline. After the course, the majority of the participants (> 70%) had at least some confidence in 5 of the 6 topics.

Conclusions
In EDs with limited resources, a longitudinal PoCUS educational curriculum is effective in improving the knowledge and comfort of physicians with limited PoCUS experience. The effectiveness of scheduled, repeated courses to refresh and refocus participants was highlighted following the unexpected challenges encountered during the course, including multiple natural disasters.
Inequalities of Green’s functions and positive solutions to nonlocal boundary value problems
Authors: Fan Shijie , Wen Pengxu , Zhang Guowei 
Published: April 2020

AbstractIn this paper, we discuss the positive solutions of beam equations with the nonlinearities including the slope and bending moment under nonlocal boundary conditions involving Stieltjes integrals. We pose some inequality conditions on nonlinearities and the spectral radius conditions on associated linear operators. These conditions mean that the nonlinearities have superlinear or sublinear growth. The existence of positive solutions is obtained by fixed point index on cones in $C^{2}[0,1]$C2[0,1], and some examples are given for beam equations subject to mixed integral and multi-point boundary conditions with sign-changing coefficients.
Comparative effect of dipeptidyl-peptidase 4 inhibitors on laboratory parameters in patients with diabetes mellitus
Authors: Nishida Yayoi , Takahashi Yasuo , Tezuka Kotoe , Akimoto Hayato , Nakayama Tomohiro , Asai Satoshi 
Published: April 2020

Abstract
Background
The purpose of this study was to evaluate and compare the effects on laboratory parameters among monotherapy with five DPP-4 inhibitors in patients with type 2 diabetes mellitus (DM).

Methods
We identified cohorts of new sitagliptin users (n = 879), vildagliptin users (n = 253), teneligliptin users (n = 260), alogliptin users (n = 237), and linagliptin users (n = 180) in patients with type 2 DM. We used a multivariate regression model to evaluate and compare the effects of the drugs on laboratory parameters including HbA1c concentration and serum concentrations of creatinine, estimated glomerular filtration rate, high density lipoprotein, total cholesterol, triglyceride, aspartate aminotransferase, and alanine aminotransferase among the five DPP-4 inhibitors up to 12 months.

Results
Our study showed a favorable effect on HbA1c concentration and a slightly unfavorable effect on serum creatinine concentration in users of the five DPP-4 inhibitors, a favorable effect on lipid metabolism in sitagliptin, vildagliptin, and alogliptin users, and a favorable effect on hepatic parameters in sitagliptin, alogliptin, and linagliptin users, in comparison of the baseline and exposure periods. However, there was no significant difference in mean change in the concentration of any laboratory parameter among the five groups of DPP-4 inhibitor users.

Conclusions
In this study, we showed the effect of five DPP-4 inhibitors on glycemic, renal, and lipid metabolism, and hepatic parameters. DPP-4 inhibitors are well-tolerated hypoglycemic drugs.
Knowledge and attitudes towards antibiotic use and resistance among undergraduate healthcare students at University of Rwanda
Authors: Nisabwe Lyduine , Brice Hirwa , Umuhire Marie Christine , Gwira Olivia , Harelimana Jean De Dieu , Nzeyimana Zephanie , Sebatunzi Osee Rurambya , Rusingiza Emmanuel Kamanzi , Hahirwa Innocent , Muvunyi Claude Mambo 
Published: April 2020

Abstract
Background
Antimicrobial resistance (AMR) is an imminent threat to modern medicine. As the efficacy of treatment regimens is reduced, mortality and morbidity attributed to infectious diseases is expected to rise dramatically across the globe. Antimicrobial stewardship and good prescription practices are critical to conserving available therapeutics; it is appropriate, therefore, to appraise our attitudes and knowledge of antimicrobial resistance, particularly for the future healthcare practitioners.

Methods
This is a descriptive cross-sectional study that was conducted among 282 medicals, dental and pharmacy students from the University of Rwanda. Questionnaires were used to collect data from the 4th to 29th March 2017.

Results
Students from Level 3 to level 6 have demonstrated a good knowledge on antibiotics and antimicrobial resistance. Generally, 95% (n = 218) agreed that the inappropriate use of antibiotics could lead to antibiotic resistance. It was found that 96% (n = 220) of the respondents had heard about AMR outside their degree courses. 49% (n = 112) of the participants reported that they are able to purchase antibiotics without a prescription. 96% (n = 220) agreed that it was important for healthcare students to be knowledgeable about antimicrobial resistance. Perhaps most surprisingly, it was found that 83% (n = 191) of participants were unfamiliar with the concept of antimicrobial stewardship and 49% (n = 21) had not yet discussed antimicrobial resistance as part of their education, albeit only 1% (n = 3) was completely unfamiliar with the term. Furthermore, 38% (n = 86) did not support that the antibiotics were overused in Rwanda, 23% (n = 10) did not agree that inappropriate antimicrobial use contributed to antimicrobial resistance, and 50% (n = 22) of participants agreed that antibiotics were indicated in the treatment of pain and inflammation.

Conclusions
The present study reports a moderate knowledge on AMR among the healthcare students. The gaps in the current formal training of healthcare individuals have been identified as well. We highlight the necessity to enhance educational approaches to introduce the key concepts of AMR and antimicrobial stewardship to the curriculum of healthcare students.
Factors influencing participation of underrepresented students in STEM fields: matched mentors and mindsets
Authors: Kricorian Katherine , Seu Michelle , Lopez Daniel , Ureta Elsie , Equils Ozlem 
Published: April 2020

Abstract
Background
Women and ethnic minorities remain underrepresented in science, technology, engineering, and math (STEM) fields. The goal of this pilot study is to better understand the beliefs and experiences of underrepresented US students pursuing STEM. Our focus was to gain insights into their mentorship experiences and preferences regarding having mentors who are gender and ethnicity matched. Environmental and psychological factors associated with participants’ decision to pursue STEM, such as family influences, academic mindsets, and attitudes towards STEM, were also studied.

Methods
We developed a survey tool based on published literature and established instruments, including measures of STEM belonging, science identity, and growth mindset, as well as measures assessing students’ views on their STEM participation. We surveyed members of a STEM-focused non-profit who were in college, graduate school, or were recent graduates.

Results
Forty-eight adults currently pursuing STEM responded to the survey. The majority (71%) were female and nearly all (96%) identified as an ethnic minority. Most reported knowing someone of their same gender (68%) or ethnicity (66%) with a STEM career who served as a role model. The majority (54%) stated that meeting a STEM professional of their own gender and ethnicity would be effective encouragement to pursue STEM. A similar percentage (56%) believed that media exposure to gender- and ethnicity-matched STEM professionals would be effective encouragement. Most (73%) demonstrated a growth mindset and had strong family support to pursue STEM (68%). Only two-thirds (66%) felt they belonged in STEM careers, and 30% agreed that people in their STEM classes are a lot like them.

Conclusion
This study contributes additional information on the views and experiences of diverse students actively pursuing STEM. Most participants indicated the importance of meeting and being mentored in STEM by those of their same gender and ethnicity, either in person or through media. Future educational efforts to increase STEM diversity should consider students’ mentorship preferences and facilitate interactions with matched-background mentors accordingly, with consideration given to the use of media. Educators should focus on inclusive learning by highlighting the accomplishments of diverse STEM professionals, to help strengthen feelings of STEM belonging.
Multiple cholangiocarcinomas in the intrahepatic and extrahepatic biliary tree due to dichloromethane exposure: a case report
Authors: Ogawa Daisuke , Hayashi Hiromitsu , Kitamura Fumimasa , Uemura Norio , Miyata Tatsunori , Okabe Hirohisa , Imai Katsunori , Yamasita Yoichi , Kubo Shoji , Baba Hideo 
Published: April 2020

Abstract
Background
An outbreak of cholangiocarcinoma in Japan has led to widespread concern among workers in printing plants. In March 2013, the Japanese Ministry of Health, Labour and Welfare, confirmed a causal relationship between cholangiocarcinoma and long-term exposure to dichloromethane (DCM) and 1,2-dichloropropane (DCP), which were widely used in printing plants. We herein report a rare case of successful radical resection of multiple cholangiocarcinomas in the intrahepatic and extrahepatic bile ducts caused by past exposure to DCM.

Case presentation
A 54-year-old man developed brown urine 22 years after his last exposure to DCP and DCM. He had an 11-year history of working at a printing plant from the age of 21 to 31 years and dealt with organic solvents during his employment. Enhanced computed tomography revealed a thickened distal bile duct wall with upstream biliary dilatation and multiple intrahepatic cholangiocarcinomas located in liver segments III, VI, and VIII. Biopsy of the distal bile duct wall revealed adenocarcinoma, and a diagnosis of distal cholangiocarcinoma was made. Tumor marker levels were within the reference range (carcinoembryonic antigen, 3.3 ng/mL; carbohydrate antigen 19-9, 25.4 U/mL; SPAN-1, 13 U/mL; and DUPAN-2, 33 U/mL). The multiple intrahepatic and extrahepatic bile duct cancers were treated by subtotal stomach-preserving pancreatoduodenectomy and partial hepatectomy of segments III, VI, and VIII. Pathological examination of the surgical specimens revealed multiple cholangiocarcinomas with well-differentiated adenocarcinoma in the biliary tree. The patient was still alive without recurrence 17 months after the operation.

Conclusions
We experienced a rare case of multiple cholangiocarcinomas in the intrahepatic and extrahepatic bile ducts that developed 22 years after the patient’s last exposure to DCP and DCM. Long-term and careful follow-up is required for workers with an occupational history of exposure to organic solvents because of the risk of development of cholangiocarcinoma.
Prognostic factors of delayed cerebral ischemia after subarachnoid hemorrhage including CT perfusion: a prospective cohort study
Authors: Abdel-Tawab Mohamed , Hasan Afaf A. , Ahmed Mohamed A. , Seif Hany M. A. , Yousif Hazem A. 
Published: April 2020

Abstract
Background
Delayed cerebral ischemia (DCI) is the worst sequel following subarachnoid hemorrhage (SAH), representing a challenge in prediction and prevention. The current study aims to identify the optimum predictors of DCI including CT perfusion (CTP) and to determine the best prognostic thresholds.
This prospective study included 49 SAH patients. All patients were treated with the standard therapy and underwent non-contrast CT, CTP, and CTA within 3 days after SAH. Hunt and Hess and Fisher scales were assessed besides quantitative CTP parameters. The primary endpoint was DCI within 21 days after SAH, defined as clinical deterioration or infarction.

Results
Out of 49 eligible patients with SAH, 9 patients developed DCI. Univariate analysis revealed that Hunt and Hess scale, Fisher scale, the presence of a cerebral aneurysm, and mean transit time (MTT) were predictive for DCI. Diagnostic threshold values by ROC curve analysis with optimal sensitivity and specificity were Hunt and Hess scale > 2, Fisher scale > 2, and MTT of 4.65 s.

Conclusion
MTT is a sensitive and specific predictor of DCI. However, Hunt and Hess scale has the optimal sensitivity and specificity to distinguish between patients who developed DCI and clinically stable patients.
Maternal Glycemia During Pregnancy and Child Carotid Intima Media Thickness, Pulse Wave Velocity, and Augmentation Index
Authors: Yuan Wen Lun , Lin Jinjie , Kramer Michael S , Godfrey Keith M , Gluckman Peter D , Chong Yap-Seng , Shek Lynette P , Tan Kok Hian , Chan Shiao-Yng , Eriksson Johan G , Yap Fabian , Lee Yung Seng , Choo Jonathan T L , Ling Lieng Hsi 
Published: April 2020

Abstract

Background
In women without diabetes, little is known about the consequences of hyperglycemia during pregnancy for the offspring’s cardiovascular structure and function.

Objective
To investigate the association of maternal glycemia during pregnancy with cardiovascular risk markers in their children in GUSTO, a Singaporean birth cohort study.

Methods
Around 26 weeks’ gestation, a 75 g oral glucose tolerance test was performed and fasting plasma glucose (FPG) and 2-hour postprandial plasma glucose (PPPG) concentrations were measured. Gestational diabetes mellitus (GDM) was defined using WHO 1999 diagnostic criteria. At 6 years of age, we measured the child’s carotid intima-media thickness (cIMT), carotid-femoral pulse wave velocity (cfPWV), aortic augmentation index (AIx), and blood pressure (BP). Association of maternal glycemia during pregnancy with cardiovascular risk markers in their children were analyzed using multiple linear and logistic regressions.

Results
Analysis were performed on 479 mother–child dyads. Higher maternal FPG was associated with higher cIMT and, in males, with a higher cfPWV in the offspring (adjusted β [CI 95%], cIMT: 0.08 per 10mm increase [0.02; 0.15], cfPWV: 0.36 m/s [0.01; 0.70]). Higher 2-hour PPPG was associated with higher cfPWV and AIx. Gestational diabetes mellitus was associated with higher AIx. No association was found between maternal glycemia and their offspring blood pressure.

Conclusions
among mothers without pre-existing diabetes, higher glycemia during pregnancy was associated with mild structural and functional vascular changes in their children at 6 years of age across a continuum. These results support the necessity to monitor maternal glycemia during pregnancy even in the absence of pre-existing diabetes or diagnosed GDM.