bluuebunny/crossref_metadata_2025_split huggingface dataset:
Germline genome protection: implications for gamete quality and germ cell tumorigenesis
Authors: Bloom J. C. , Loehr A. R. , Schimenti J. C. , Weiss R. S. 
Published: May 2019

AbstractBackgroundGerm cells have a unique and critical role as the conduit for hereditary information and therefore employ multiple strategies to protect genomic integrity and avoid mutations. Unlike somatic cells, which often respond to DNA damage by arresting the cell cycle and conducting DNA repair, germ cells as well as long‐lived pluripotent stem cells typically avoid the use of error‐prone repair mechanisms and favor apoptosis, reducing the risk of genetic alterations. Testicular germ cell tumors, the most common cancers of young men, arise from pre‐natal germ cells.ObjectivesTo summarize the current understanding of DNA damage response mechanisms in pre‐meiotic germ cells and to discuss how they impact both the origins of testicular germ cell tumors and their remarkable responsiveness to genotoxic chemotherapy.Materials and methodsWe conducted a review of literature gathered from PubMed regarding the DNA damage response properties of testicular germ cell tumors and the germ cells from which they arise, as well as the influence of these mechanisms on therapeutic responses by testicular germ cell tumors.Results and discussionThis review provides a comprehensive evaluation of how the developmental origins of male germ cells and their inherent germ cell‐like DNA damage response directly impact the development and therapeutic sensitivity of testicular germ cell tumors.ConclusionsThe DNA damage response of germ cells directly impacts the development and therapeutic sensitivity of testicular germ cell tumors. Recent advances in the study of primordial germ cells, post‐natal mitotically dividing germ cells, and pluripotent stem cells will allow for new investigations into the initiation, progression, and treatment of testicular germ cell tumors.
Systematic review with meta‐analysis: efficacy and safety of oral Janus kinase inhibitors for inflammatory bowel disease
Authors: Ma Christopher , Lee Jeffrey K. , Mitra Anish R. , Teriaky Anouar , Choudhary Daksh , Nguyen Tran M. , Vande Casteele Niels , Khanna Reena , Panaccione Remo , Feagan Brian G. , Jairath Vipul 
Published: May 2019

SummaryBackgroundJanus kinase (JAK) inhibitors represent a novel therapeutic class for treatment of inflammatory bowel disease.AimsTo determine the efficacy and safety of JAK inhibitors compared to placebo for the treatment of Crohn's disease (CD) and ulcerative colitis (UC).MethodsPubMed, Embase and CENTRAL were systematically searched to November 1, 2018. Randomised placebo‐controlled trials (RCTs) of JAK inhibitors in adult patients with CD or UC were eligible. Open‐label extension studies without a placebo comparator arm were excluded. Clinical, endoscopic, and safety outcomes were extracted and rates relative to placebo were pooled using a random‐effects model.ResultsA total of 12 RCTs (5 CD, 7 UC) were included. Patients were randomised to placebo (n = 844), tofacitinib (n = 1882), filgotinib (n = 130), peficitinib (n = 176), upadacitinib (n = 387) or TD‐1473 (n = 31). JAK inhibitor treatment was associated with induction of clinical remission in CD (RR, relative risk 1.38 [95% confidence interval CI 1.04‐1.83], P = 0.025, I2 = 14%) and UC (RR 3.07 [95% CI 2.03‐4.63], P < 0.001, I2 = 0%). In UC, JAK inhibitor treatment was associated with induction of endoscopic remission (endoscopic Mayo subscore MCSe = 0/1) (RR 2.43 [95% CI 1.64‐3.59], P < 0.001, I2 = 27%) and mucosal healing (MCSe = 0) (RR 5.50 [95% CI 2.46‐12.32], P < 0.001, I2 = 0%). JAK inhibitor treatment increased the risk of infection compared to placebo (RR 1.40 [95% CI 1.18‐1.67], P < 0.001, I2 = 0%), particularly for herpes zoster.ConclusionsJAK inhibitors are effective for inducing clinical remission in CD and induction of clinical and endoscopic remission in UC, although are associated with an increased risk of infectious complications.
Evolutionary stakeholder theory and public utility regulation
Authors: Kline William , McDermott Karl 
Published: May 2019

AbstractPublic utility regulation is one example of how stakeholder theory has actually evolved in practice. Through trial and error, court cases, statutory law and economic realities, stakeholder theory has its origins almost a century before R Edward Freeman published his seminal workStrategic Management: A Stakeholder Approach. This wealth of historical data is largely overlooked by the stakeholder literature. We will show in this article how the specific history of public utility regulation provides at least one answer to how stakeholder theory can be formulated, used, and applied. Thisprocessof determining and protecting stakeholder interests is significantly different from rationalist trends in stakeholder theory.1Rather than first trying to determine the requirements of stakeholder theory in conjunction with an ideal ethical theory, the account given here is of anevolutionary stakeholder theorywhere rules arise out of the ongoing search for cooperative solutions among all stakeholders.
Tumor‐associated macrophages promote bladder tumor growth through PI3K/AKT signal induced by collagen
Authors: Qiu Shi , Deng Linghui , Liao Xinyang , Nie Ling , Qi Fang , Jin Kun , Tu Xiang , Zheng Xiaonan , Li Jiakun , Liu Liangren , Liu Zhenhua , Bao Yige , Ai Jianzhong , Lin Tianhai , Yang Lu , Wei Qiang 
Published: May 2019

AbstractThe tumor microenvironment is associated with various tumor progressions, including cancer metastasis, immunosuppression, and tumor sustained growth. Tumor‐associated macrophages (TAMs) are considered an indispensable component of the tumor microenvironment, participating in the progression of tumor microenvironment remodeling and creating various compounds to regulate tumor activities. This study aims to observe enriched TAMs in tumor tissues during bladder cancer development, which markedly facilitated the proliferation of bladder cancer cells and promoted tumor growth in vivo. We determined that TAMs regulate tumor sustained growth by secreting type I collagen, which can activate the prosurvival integrin α2β1/PI3K/AKT signaling pathway. Furthermore, traditional chemotherapeutic drugs combined with integrin α2β1 inhibitor showed intensive anticancer effects, revealing an innovative approach in clinical bladder cancer treatment.
Allele frequency of pathogenic variants related to adult‐onset Mendelian diseases
Authors: Li Xiang , Jin Yan , Yin Yuxin 
Published: May 2019

AbstractAn increasing number of variants related to Mendelian diseases have been discovered through analyses of next‐generation sequencing data, but the results related to adult‐onset Mendelian diseases are insufficient. One possible explanation is that the methods commonly used to evaluate pathogenic variants in patients with congenital Mendelian diseases may not be appropriate for adult‐onset diseases due to differences in selection pressure, particularly when assessing the frequency of variants in the general population. We established a well‐processed and filtered database of pathogenic variants with both phenotype and frequency information based on the ClinVar and GnomAD public database to better explore the genetic features of adult‐onset diseases under real‐world conditions. Compared with the control group, pathogenic variants related to adult‐onset dominant diseases had a higher allele frequency pattern. Further, the allele frequency patterns of both dominant and recessive variants were higher in patients with neurodegenerative diseases than those in patients with intellectual disabilities. Based on the mutation‐selection balance model, the above observation of allele frequency described the lower selection pressure on pathogenic variants related to adult‐onset Mendelian diseases and suggests a lower effectiveness of population and loss‐of‐function evidence in investigations of adult‐onset Mendelian diseases.
Efficient solution to the millionaires' problem based on asymmetric commutative encryption scheme
Authors: Liu Meng , Luo Yun , Nanda Priyadarsi , Yu Shui , Zhang Jianbing 
Published: May 2019

AbstractSecure multiparty computation is an important scheme in cryptography and can be applied in various real‐life problems. The first secure multiparty computation problem is the millionaires' problem, and its protocol is an important building block. Because of the less efficiency of public key encryption scheme, most existing solutions based on public key cryptography to this problem are inefficient. Thus, a solution based on the symmetric encryption scheme has been proposed. In this paper, we formally analyse the vulnerability of this solution, and propose a new scheme based on the decisional Diffie‐Hellman assumption. Our solution also uses 0‐encoding and 1‐encoding generated by our modified encoding method to reduce the computation cost. We implement the solution based on symmetric encryption scheme and our protocol. Extensive experiments are conducted to evaluate the efficiency of our solution, and the experimental results show that our solution can be much more efficient and be approximately 8000 times faster than the solution based on symmetric encryption scheme for a 32‐bit input and short‐term security. Moreover, our solution is also more efficient than the state‐of‐the‐art solution without precomputation and can also compare well with the state‐of‐the‐art protocol while the bit length of private inputs is large enough.
Pulse wave velocity to the global longitudinal strain ratio in survivors of myocardial infarction
Authors: Wykretowicz Andrzej , Schneider Agata , Krauze Tomasz , Szczepanik Adam , Banaszak Agnieszka , Minczykowski Andrzej , Piskorski Jaroslaw , Guzik Przemyslaw 
Published: May 2019

AbstractBackgroundNew index of pulse wave velocity to global longitudinal peak systolic strain (PWV/GLPSS) was reported to be associated with cardiovascular damage. We evaluated the prognostic role of this metric in survivors of acute myocardial infarction (AMI).Material and methodsWe investigated in 569 patients with AMI, whether PWV/GLPSS was associated with a composite endpoint of death, stroke or new myocardial infarction, in long‐term follow‐up. Left ventricular longitudinal strain was evaluated by speckle tracking, and carotid arterial stiffness (local PWV) was determined using radiofrequency data technology.ResultsDuring follow‐up (median 1316 days), 114 subjects reached composite endpoint. These subjects were significantly older (P < 0.0001) and were characterized by lower ejection fraction (P < 0.0001), lower GLPSS (P < 0.0001), higher PWV (P = 0.007) and lower PWV/GLPSS index (P < 0.0001). Patients with PWV/GLPSS <−0.74 were at a significantly higher risk for the composite endpoint during the follow‐up (hazard rate: 1.7; 95% confidence interval: 1.2‐2.6; P < 0.001). The PWV/GLPSS was additive to the predictive value of EF < 35%—patients with PWV/GLPSS <−0.74 and EF < 35% had the highest risk for the endpoint events.ConclusionsThe current study shows that PWV/GLPSS index has significant, independent and additive value in predicting CV complications, in subjects with myocardial infarction.
Fertility and marital status in adults with childhood onset epilepsy: A population‐based cohort study
Authors: Starck Christian , Nevalainen Olli , Auvinen Anssi , Eriksson Kai 
Published: May 2019

AbstractObjectiveOur objective was to explore the association of childhood onset epilepsy (COE) and clinical factors on marital status and fertility in adulthood.MethodsWe identified a population‐based cohort of 307 individuals with COE treated in the Tampere University Hospital district with an inception date of December 31, 1992. A matched reference cohort of 1244 individuals without COE was established as a random sample of the population in the study area through the Population Register Center (PRC). The PRC also provided data on marriages and offspring up to 2018. Fertility and marriage analysis was done by calculating the time until first child and marriage. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated with Cox regression for follow‐up spanning up to January 2018.ResultsPatients with COE had lower fertility rates (32.2% vs 57.3% any offspring, HR = 0.47, 95% CI = 0.38‐0.58) and fewer marriages (28.3% vs 49.7% ever married, HR = 0.49, 95% CI = 0.39‐0.61) than the referents without COE during 25‐year follow‐up. The largest impact was in patients with COE who had any disability (10.1% any offspring, HR = 0.20, 95% CI = 0.10‐0.41; 6.5% ever married, HR = 0.11, 95% CI = 0.06‐0.21), symptomatic etiology of epilepsy (13.1%, HR = 0.18, 95% CI = 0.11‐0.31; 12.1%, HR = 0.21, 95% CI = 0.12‐0.36), onset of epilepsy before 2 years of age (HR = 0.20, 95% CI = 0.12‐0.31; HR = 0.29, 95% CI = 0.18‐0.46), and high seizure frequency after start of treatment (HR = 0.13, 95% CI = 0.06‐0.28; HR = 0.20, 95% CI = 0.10‐0.41). Patients with COE without any disabilities had only slightly lowered fertility (HR = 0.76, 95% CI = 0.61‐0.95) and a nonsignificant reduction in marriages (HR = 0.80, 95% CI = 0.64‐1.02).SignificanceCOE was associated with a lower chance of finding a partner at adulthood and having fewer children. The extent of such effect varied between patient subgroups.
Healthy African American Families in the 21st Century: Navigating Opportunities and Transcending Adversities
Authors: Murry Velma McBride 
Published: May 2019

ObjectiveTo identify pathways through which African American families successfully negotiate and navigate stressful life events to facilitate positive family functioning, relationships, and healthy developmental outcomes in their children.BackgroundDespite the advancement of African Americans since passing of the 1965 Civil Rights Act, racism remains a major stressor that affects everyday life experiences of 21st‐century African American families. Little is known about the cascading effects of race‐related exposure on processes in African American families, nor about what promotes healthy functioning among African American families.MethodThree waves of data on 867 families participating in the Family and Community Health Study were analyzed to identify pathways that forecast family functioning and developmental outcomes of youth as they transitioned from middle childhood to late adolescence.ResultsStressful life events heightened maternal depression and anxiety, which were associated with a more cynical and hostile worldview and poorer quality of family relations. Parenting practices and family relationship quality were linked with children's self‐pride, which was closely associated with more optimistic worldview. Self‐pride was also associated with future aspirations among youth, and future‐oriented youth tended to engage in fewer self‐harm behaviors as they transitioned from middle childhood to early adolescence.ConclusionReframing one's life situation, despite exposure to racial discrimination, serves a protective function for African American families. Exerting a sense of agency, internal will, capacity, and strength are effective strategies to transcend adversities.ImplicationsThat positive worldview can render more manageable family outcomes for African Americans, regardless of socioeconomic status, is worth considering in research, clinical practice, and preventive interventions.
Facies selectivity of benthic invertebrates in a Permian/Triassic boundary microbialite succession: Implications for the “microbialite refuge” hypothesis
Authors: Foster William J. , Lehrmann Daniel J. , Yu Meiyi , Martindale Rowan C. 
Published: May 2019

AbstractThrombolite and stromatolite habitats are becoming increasingly recognized as important refuges for invertebrates during Phanerozoic Oceanic Anoxic Events (OAEs); it is posited that oxygenic photosynthesis by cyanobacteria in these microbialites provided a refuge from anoxic conditions (i.e., the “microbialite refuge” hypothesis). Here, we test this hypothesis by investigating the distribution of ~34, 500 benthic invertebrate fossils found in ~100 samples from a microbialite succession that developed following the latest Permian mass extinction event on the Great Bank of Guizhou (South China), representing microbial (stromatolites and thrombolites) and non‐microbial facies. The stromatolites were the least taxonomically diverse facies, and the thrombolites also recorded significantly lower diversities when compared to the non‐microbial facies. Based on the distribution and ornamentation of the bioclasts within the thrombolites and stromatolites, the bioclasts are inferred to have been transported and concentrated in the non‐microbial fabrics, that is, cavities around the microbial framework. Therefore, many of the identified metazoans from the post‐extinction microbialites are not observed to have been living within a microbial mat. Furthermore, the lifestyle of many of the taxa identified from the microbialites was not suited for, or even amenable to, life within a benthic microbial mat. The high diversity of oxygen‐dependent metazoans in the non‐microbial facies on the Great Bank of Guizhou, and inferences from geochemical records, suggests that the microbialites and benthic communities developed in oxygenated environments, which disproves that the microbes were the source of the oxygenation. Instead, we posit that microbialite successions represent a taphonomic window for exceptional preservation of the biota, similar to a Konzentrat‐Lagerstätte, which has allowed for diverse fossil assemblages to be preserved during intervals of poor preservation.
Field Trials of Chaotic Advection to Enhance Reagent Delivery
Authors: Cho Michelle S. , Solano Felipe , Thomson Neil R. , Trefry Michael G. , Lester Daniel R. , Metcalfe Guy 
Published: May 2019

AbstractChaotic advection is a novel approach that has the potential to enhance contact between an injected reagent and target contaminants, and thereby improve the effectiveness of in situ treatment technologies. One configuration that is capable of generating chaotic advection is termed the rotated potential mixing (RPM) flow. A conventional RPM flow system involves periodically reoriented dipole flow driven by transient switching of pressures at a series of radial wells. To determine whether chaotic advection can be engineered using such an RPM flow system, and to assess the consequent impact on the spatial distribution of a conservative tracer, a series of field‐scale experiments were conducted. These experiments involved the injection of a tracer in the center of a circular array of wells followed by either mixing using an engineered RPM flow system to invoke chaotic advection, or by natural processes (advection and diffusion) as the control. Pressure fluctuations from the mixing tests using the RPM flow system showed consistent peak amplitudes during injection and extraction at a frequency corresponding to the switching time, suggesting that the target hydraulic behavior was achieved with the time‐dependent flow field. The tracer breakthrough responses showed oscillatory behavior at all monitoring locations during the mixing tests which indicated that the desired RPM flow was generated. The presence of chaotic advection was supported by comparisons to observations from a previous laboratory experiment using RPM flow, and the Fourier spectrum of the temporal tracer data. Results from several quantitative metrics adopted to demonstrate field‐scale evidence of chaotic advection showed that mixing led to improved lateral tracer spreading and approximately uniform concentrations across the monitoring network. The multiple lines of evidence assembled in this proof‐of‐concept study conclusively demonstrated that chaotic advection can be engineered at the field scale. This investigation is a critical step in the development of chaotic advection as a viable and efficient approach to enhance reagent delivery.
Effectiveness of a hepatitis B vaccination program at two tertiary hemodialysis centers
Authors: Kufta Lindsay , Shalansky Karen F. , Jastrzebski Jacek , Lau Wynnie 
Published: May 2019

AbstractIntroduction: Hemodialysis (HD) patients are at increased risk of hepatitis B infection in comparison to the general population. Despite a more intensified hepatitis vaccination regimen, response rates in HD patients are typically low. The study was conducted to quantify response rate to a new hepatitis B vaccination protocol initiated in late 2015, determine risk factors affecting response rate, and assess adherence to protocol.Methods: This retrospective chart review evaluated all HD patients eligible for hepatitis B vaccination in two large dialysis clinics from initiation of the hepatitis B protocol to July 2017. Recombinant hepatitis vaccine (Recombivax® HB) 40 μg was administered in a 3‐dose regimen at months 0, 1, and 6 to patients with hepatitis B surface antibodies (anti‐HBs) <10 mIU/mL. A repeat series was given if anti‐HBs levels remained below 10 mIU/mL after the first series. A booster dose was given if anti‐HBs titers fell below 10 mIU/mL after initial response to a second series vaccination.Findings: Of 411 patients at the two HD centers, 142 patients received hepatitis B vaccination with a total of 168 vaccine courses given, series 1: n = 86, series 2: n = 60 and booster: n = 22. Response rates to vaccination were 61.4%, 58.3%, and 81.8%, respectively. In univariate analysis, adherence to protocol significantly affected response rate (P = 0.035). A multivariate analysis assessing response rates to series 1, 2 or booster confirmed that adherence was a significant risk factor (OR = 2.2; 95% CI 1.4–3.4; P = 0.0005).Discussion: This was the first study to examine adherence to regimen and identified adherence as an important predictor of vaccine response. Adherence is one of the few modifiable risk factors that can be optimized in an effort to improve response to hepatitis B vaccination.
Development and characterization of novel anti‐C5 monoclonal antibodies capable of inhibiting complement in multiple species
Authors: Zelek Wioleta M. , Taylor Philip R. , Morgan B. Paul 
Published: May 2019

SummaryOver the last decade there has been an explosion in complement therapies; one‐third of the drugs in the clinic or in development target C5 protein. Eculizumab, a monoclonal antibody (mAb) that binds C5 and blocks its cleavage by the convertase, is the current reference standard treatment for atypical haemolytic uraemic syndrome (aHUS) and paroxysmal nocturnal haemoglobinuria (PNH) and in clinical trials for many other diseases. Here we describe a panel of novel anti‐C5 mAb, including mAb that, like Eculizumab, are efficient inhibitors of complement but, unlike Eculizumab, inhibit across species, including human, rat, rabbit and guinea pig. Several inhibitory anti‐C5 mAb were identified and characterized for C5 binding and lytic inhibitory capacity in comparison to current therapeutic anti‐C5 mAb; three clones, 4G2, 7D4 and 10B6, were selected and further characterized for ligand specificity and affinity and cross‐species inhibitory activity. The mAb 10B6 was human‐specific whereas mAb 4G2 and 7D4 efficiently inhibited lysis by human, rabbit and rat serum, and weakly inhibited guinea pig complement; 7D4 also weakly inhibited mouse complement in vitro The rat C5‐cross‐reactive mAb 4G2, when administered intraperitoneally in a rat model of myasthenia gravis, effectively blocked the disease and protected muscle endplates from destruction. To our knowledge this is the first report of an anti‐C5 function blocking mAb that permits preclinical studies in rats.