bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retinal oxygen saturation is associated with HbA1c but not with short‐term diabetes control, internal environment, smoking and mild retinopathy ‐ ROXINEGLYD study
Authors: Mlčák Petr , Chlup Rudolf , Kudlová Pavla , Krystyník Ondřej , Král Michal , Kučerová Veronika , Spurná Jaromíra , Titzová Simona , Hübnerová Petra , Vláčil Ondřej , Šínová Irena , Karhanová Marta , Zapletalová Jana , Šín Martin 
Published: March 2021

AbstractPurposePurpose of this prospective uncontrolled single‐centre pilot study was to find an association of retinal oxygen saturation (SatO2) with acid–base balance (ABB), carboxyhaemoglobin concentration, current plasma glucose concentration (PG), mean PG and PG variability over the last 72 hr, haemoglobin A1c (HbA1c), and other conditions.MethodsForty‐one adults (17 men) with type 1 (N = 14) or type 2 (N = 27) diabetes mellitus, age 48.6 ± 13.5 years, diabetes duration 9 (0.1–36) years, BMI 29.4 ± 6.3 kg/m2, and HbA1c 52 ± 12.7 mmol/mol completed the study. The 4‐day study comprised two visits (Day l, Day 4) including 72 hr of continuous glucose monitoring (CGM) by iPro®2 Professional CGM (Medtronic, MiniMed, Inc., Northridge, CA, USA). Retinal oximeter Oxymap T1 (Oxymap ehf., Reykjavik, Iceland) was used to assess SatO2.ResultsWilcoxon signed‐rank test showed no SatO2 difference between eyes and visits. Spearman's correlation analysis revealed a significant correlation between arterial SatO2 and PG variability in type 2 diabetes mellitus, a positive correlation of venous SatO2 with HbA1c and with finger pulse oximetry. However, no correlation of SatO2 with ABB, carboxyhaemoglobin, current PG, mean PG over the 72 hr, age, diabetes duration, BMI, lipoproteinaemia, body temperature, systolic and diastolic blood pressure, heart rate, central retinal thickness and retinal nerve fibre layer thickness was found.ConclusionThis study confirmed the association of venous SatO2 with long‐term but not with short‐term diabetes control, ABB and other conditions. The increased SatO2 and questionable impact of PG variability on retinal SatO2 is a research challenge.
Parapapillary deep‐layer microvasculature dropout is only found near the retinal nerve fibre layer defect location in open‐angle glaucoma
Authors: Son Ki Young , Han Jong Chul , Kee Changwon 
Published: March 2021

AbstractPurposeWe aimed to investigate the topographic correspondence between deep‐layer microvasculature dropout (MvD) and retinal nerve fibre layer (RNFL) defects in eyes with open‐angle glaucoma (OAG) using spectral‐domain optical coherence tomography (SD‐OCT) and optical coherence tomography angiography (OCT‐A).MethodsMicrovasculature dropout width and location were determined using OCT‐A, RNFL thickness, RNFL defect width and location were revealed using SD‐OCT. The association between MvD and RNFL widths and that between the location of the MvD and RNFL defects were investigated. In addition, patients with OAG were divided into two groups: the RNFL defect in one hemiretina (RNFLD‐HR) group (n = 24 eyes) and the RNFL defects in both hemiretinas (RNFLD‐BR) group (n = 25 eyes). The presence, width and location of MvDs were compared between the two groups.ResultsForty‐nine eyes were included. In 24 RNFLD‐HR eyes, all MvDs were found in the inferior area, corresponding with the location of the RNFL defect. Meanwhile, in 25 RNFLD‐BR eyes, 18 MvDs (72%) were found in the inferior hemiretina, two (8%) were found in the superior hemiretina, and five (20%) were found in both hemiretinas. In RNFLD‐BR eyes, the average RNFL thickness was thinner in a location with MvD than a location without MvD.ConclusionConsidering that MvD is only observed at the location of the RNFL defect in RNFLD‐HR eyes and is usually found in the location of more severe RNFL defects in RNFLD‐BR eyes, MvD seems to be a sign that accompanies glaucomatous damage in OAG eyes.
Glomerular filtration and shrunken pore syndrome in children and adults
Authors: Grubb Anders 
Published: March 2021

AbstractA major function of the kidney is to, by glomerular filtration, maintain the overall steady‐state of 5–30 kDa proteins, many of which are signalling molecules. This function of the kidney has been overlooked, since predominantly low‐molecular‐mass substances <1 kDa have been used to measure or estimate glomerular filtration rate (GFR). The use of cystatin C (13 kDa) as a marker of GFR has allowed the discovery that the filtration of 5–30 kDa molecules can be selectively impaired defining the shrunken pore syndrome. The discovery, pathophysiology, morbidity (mainly cardiovascular manifestations) and mortality of this syndrome are described.
Thyroid function in postpartum psychosis: An exploratory study
Authors: Sethy Rati Ranjan , Garg Shobit , Ram Daya , Tikka Sai Krishna 
Published: March 2021

AbstractThe study aimed to compare thyroid function between psychosis with postpartum onset (PPO), psychosis without postpartum onset (PWPO), and normal postpartum females (HC). Twenty women were recruited in each of the three groups. The PPO group had significantly greater psychopathology and shorter episodes compared to the PWPO group. The PPO group was found to have significantly greater right lobe volume than the other groups. The PPO group also had significantly higher FT4 levels than the HC group. We conclude that isolated increase in FT4 and thyroid lobe volumetric changes could be more specifically associated with psychosis of post‐partum onset.
Women's evaluation of costs and benefits in public versus private spheres: The role of gender ideology
Authors: Villanueva‐Moya Laura , Expósito Francisca 
Published: March 2021

AbstractGender equality's progress in the public sphere has not expanded to the private sphere, where women are primarily responsible for housework, which seems to affect them at individual, family, and social levels. We investigated how women perceive contextual (society), intrapersonal (decision‐making), or interpersonal (romantic relationship) factors could affect them (cost and benefits) at these levels; considering women's gender ideology as moderator. In Study 1, women (N = 94) rated the associated costs and benefits of a context (equal vs. unequal) and a decision (work vs. family). Findings showed that an equal context and the decision to invest in work benefited women at the individual level; investing in work benefited women at the social level but not at the family level. Moreover, women's gender ideology affected their evaluation. The Study 2 focused on the private sphere, women (N = 91) rated the associated costs and benefits of an egalitarian (vs. traditional) partner. Women perceived more benefits at all levels in an egalitarian (vs. traditional) partner. The effect a partner's ideology had on women's perception was stronger than the women's ideology. These findings highlight that—although women progress in the public sphere—certain factors in the private sphere seem to affect them.
Evaluation of the protective effect of lycopene on growth performance, intestinal morphology, and digestive enzyme activities of aflatoxinB1 challenged broilers
Authors: Sarker Md Touhiduzzaman , Wang Zhi Yue , Yang Haiming , Wan Xiaoli , Emmanuel Asare 
Published: March 2021

AbstractThe current study was conducted to investigate the protective efficiency of dietary lycopene (LYC) supplementation on growth performance, intestinal morphology, and digestive enzyme activities aflatoxinB1 (AFB1) challenged broilers. A total of 240 days old Arber across male broiler chicks were randomly allocated in five treatments and six replicates (eight birds per replicate); feed and water were provided ad libitum during the 42 days experiment. The treatment diets were as follows: (i) Basal diet (control), (ii) Basal diet + 100 µg/kg AFB1 contaminated diet, (iii) Basal diet + 100 µg/kg AFB1 + 100 mg/kg LYC1, (iv) Basal diet + 100 µg/kg AFB1 + 200 mg/kg LYC2, and (v) Basal diet + 100 µg/kg AFB1 + 400 mg/kg LYC3. The results showed that the addition of LYC to AFB1 contaminated broiler diets significantly increased (p < .05) average daily gain (ADG) and decreased feed conversion ratio (FCR) compared to the AFB1 diet. AFB1 diet decreased the intestinal villus height (VH) and crypt depth ratio (VCR) while increasing the crypt depth (CD). However, dietary LYC supplemented diets relieved the intestinal morphological alterations. Dietary LYC supplementation (200 and 400 mg/kg) significantly improved (p < .05) intestinal digestive enzyme amylase and lipase activities with AFB1 contaminated diet. These findings suggested that LYC is a promising feed supplement in the broiler industry, alleviating the harmful effects of AFB1.
The effect of interleukin‐17F on vasculogenic mimicry in oral tongue squamous cell carcinoma
Authors: Almahmoudi Rabeia , Salem Abdelhakim , Hadler‐Olsen Elin , Svineng Gunbjørg , Salo Tuula , Al‐Samadi Ahmed 
Published: March 2021

AbstractOral tongue squamous cell carcinoma (OTSCC) is one of the most common cancers worldwide and is characterized by early metastasis and poor prognosis. Recently, we reported that extracellular interleukin‐17F (IL‐17F) correlates with better disease‐specific survival in OTSCC patients and has promising anticancer effects in vitro. Vasculogenic mimicry (VM) is the formation of an alternative vasculogenic system by aggressive tumor cells, which is implicated in treatment failure and poor survival of cancer patients. We sought to confirm the formation of VM in OTSCC and to investigate the effect of IL‐17F on VM formation. Here, we showed that highly invasive OTSCC cells (HSC‐3 and SAS) form tube‐like VM on Matrigel similar to those formed by human umbilical vein endothelial cells. Interestingly, the less invasive cells (SCC‐25) did not form any VM structures. Droplet‐digital PCR, FACS, and immunofluorescence staining revealed the presence of CD31 mRNA and protein in OTSCC cells. Additionally, in a mouse orthotopic model, HSC‐3 cells expressed VE‐cadherin (CD144) but lacked Von Willebrand Factor. We identified different patterns of VM structures in patient samples and in an orthotopic OTSCC mouse model. Similar to the effect produced by the antiangiogenic drug sorafenib, IL‐17F inhibited the formation of VM structures in vitro by HSC‐3 and reduced almost all VM‐related parameters. In conclusion, our findings indicate the presence of VM in OTSCC and the antitumorigenic effect of IL‐17F through its effect on the VM. Therefore, targeting IL‐17F or its regulatory pathways may lead to promising therapeutic strategies in patients with OTSCC.
Ppp6c haploinsufficiency accelerates UV‐induced BRAF(V600E)‐initiated melanomagenesis
Authors: Kanazawa Kosuke , Kishimoto Kazuhiro , Nomura Miyuki , Kurosawa Koreyuki , Kato Hiroyuki , Inoue Yui , Miura Koh , Fukui Katsuya , Yamashita Yoji , Sato Ikuro , Tsuji Hiroyuki , Watanabe Toshio , Tanaka Takuji , Yasuda Jun , Tanuma Nobuhiro , Shima Hiroshi 
Published: March 2021

AbstractAccording to TCGA database, mutations in PPP6C (encoding phosphatase PP6) are found in c. 10% of tumors from melanoma patients, in which they coexist with BRAF and NRAS mutations. To assess PP6 function in melanoma carcinogenesis, we generated mice in which we could specifically induce BRAF(V600E) expression and delete Ppp6c in melanocytes. In these mice, melanoma susceptibility following UVB irradiation exhibited the following pattern: Ppp6c semi‐deficient (heterozygous) > Ppp6c wild‐type > Ppp6c‐deficient (homozygous) tumor types. Next‐generation sequencing of Ppp6c heterozygous and wild‐type melanoma tumors revealed that all harbored Trp53 mutations. However, Ppp6c heterozygous tumors showed a higher Signature 1 (mitotic/mitotic clock) mutation index compared with Ppp6c wild‐type tumors, suggesting increased cell division. Analysis of cell lines derived from either Ppp6c heterozygous or wild‐type melanoma tissues showed that both formed tumors in nude mice, but Ppp6c heterozygous tumors grew faster compared with those from the wild‐type line. Ppp6c knockdown via siRNA in the Ppp6c heterozygous line promoted the accumulation of genomic damage and enhanced apoptosis relative to siRNA controls. We conclude that in the presence of BRAF(V600E) expression and UV‐induced Trp53 mutation, Ppp6c haploinsufficiency promotes tumorigenesis.
Tournament incentives and performance: Evidence from the WNBA
Authors: Hill Brian 
Published: March 2021

AbstractPlayers entering the Women's National Basketball Association (WNBA) are allocated to teams based on a draft where lower performing teams in the regular season earn the highest odds of selecting the best players, creating an incentive for teams to lose games. Using data from the 2000–2019 seasons, results indicate that WNBA teams are more likely to lose after they have been eliminated from postseason playoffs regardless of the gender of the coach or general manager. Evidence of tanking is concentrated in seasons after the WNBA made a draft lottery change in 2015, which was intended to reduce tanking.
A metabolomic analysis of thiol response for standard and modified N‐acetyl cysteine treatment regimens in patients with acetaminophen overdose
Authors: Dear James W , Ng Mei Li , Bateman D. Nicholas , Leroy Sivappiragasam Pakkiri , Choi Hyungwon , Khoo Benjamin Bing Jie , Ibrahim Baharudin , Drum Chester Lee 
Published: March 2021

AbstractN‐acetylcysteine (NAC) is an antidote to prevent acetaminophen (paracetamol‐APAP)‐induced acute liver injury (ALI). The 3‐bag licensed 20.25 h standard regimen, and a 12 h modified regimen, are used to treat APAP overdose. This study evaluated the redox thiol response and APAP metabolites, in patients with a single APAP overdose treated with either the 20.25 h standard or 12 h modified regimen. We used liquid chromatography tandem mass spectrometry to quantify clinically important oxidative stress biomarkers and APAP metabolites in plasma samples from 45 patients who participated in a randomized controlled trial (SNAP trial). We investigated the time course response of plasma metabolites at predose, 12 h, and 20.25 h post‐start of NAC infusion. The results showed that the 12 h modified regimen resulted in a significant elevation of plasma NAC and cysteine concentrations at 12 h post‐infusion. We found no significant alteration in the metabolism of APAP, mitochondrial, amino acids, and other thiol biomarkers with the two regimens. We examined APAP and purine metabolism in overdose patients who developed ALI. We showed the major APAP‐metabolites and xanthine were significantly higher in patients with ALI. These biomarkers correlated well with alanine aminotransferase activity at admission. Receiver operating characteristic analysis showed that at admission, plasma APAP‐metabolites and xanthine concentrations were predictive for ALI. In conclusion, a significantly higher redox thiol response with the modified NAC regimen at 12 h postdose suggests this regimen may produce greater antioxidant efficacy. At baseline, plasma APAP and purine metabolites may be useful biomarkers for early prediction of APAP‐induced ALI.
Safety, tolerability, pharmacokinetics, and pharmacodynamics of a TLR7 agonist prodrug RO6870868 in healthy volunteers
Authors: Grippo Joseph F. , Folitar Ilia , Passe Sharon , Jiang Qiudi , Rodriguez Ignacio , Fettner Scott H. , Calleja Elizabeth 
Published: March 2021

AbstractRO6870868 is an oral prodrug of the toll‐like receptor 7 (TLR7) specific agonist, RO6871765. TLR7 agonists augment host immune activity and are in development to treat hepatitis B infection. We evaluated the safety, tolerability, pharmacokinetics (PKs), and pharmacodynamics (PDs) of RO6870868 in a first‐in‐human, phase I, randomized, single ascending oral dose study in 60 healthy volunteers at 6 dose levels (200–2000 mg). Single oral doses were generally well‐tolerated with a predictable safety profile associated with dose‐dependent increases in systemic interferon. No serious adverse events (AEs) were reported and no subject withdrew from the study due to an AE. No clinically significant changes were observed in vital signs, electrocardiograms, or laboratory parameters. Following oral RO6870868 doses, plasma RO6871765 concentrations increased rapidly, exhibiting mean terminal half‐life ranging 2–6 h across all cohorts, with area under the plasma concentration versus time curve extrapolated to infinity (AUC0‐∞) increasing proportionally with dose. A pattern of dose and time‐dependent PD activity was demonstrated consistent with engagement of the TLR7 system. Single RO6870868 doses activated components of the TLR innate immune system in a dose‐dependent manner with adequate safety and tolerability. Single‐dose data in healthy volunteers are useful to evaluate safety, PK, and PD activity of TLR7 agonists and help to guide dose and regimen selection for further trials in patients with chronic hepatitis B.
Regulatory guidelines do not accurately predict tolvaptan and metabolite interactions at BCRP, OATP1B1, and OAT3 transporters
Authors: Shoaf Susan E. , Bricmont Patricia , Repella Gordon Jennifer 
Published: March 2021

AbstractTolvaptan (TLV) was US Food and Drug Administration (FDA)‐approved for the indication to slow kidney function decline in adults at risk of rapidly progressing autosomal dominant polycystic kidney disease in 2018. In vitro, TLV was a breast cancer resistance protein (BCRP) inhibitor, whereas the oxobutyric acid metabolite of TLV (DM‐4013) was an inhibitor of organic anion transport polypeptide (OATP)1B1 and organic anion transporter (OAT)3. Based on the 2017 FDA guidance, potential for clinically relevant inhibition at these transporters was indicated for the highest TLV regimen. Consequently, two postmarketing clinical trials in healthy subjects were required. In trial 1, 5 mg rosuvastatin calcium (BCRP and OATP1B1 substrate) was administered alone, with 90 mg TLV or 48 h following 7 days of once daily 300 mg TLV (i.e., in the presence of DM‐4103). In trial 2, 40 mg furosemide (OAT3 substrate) was administered alone and in presence of DM‐4103. For BCRP, rosuvastatin geometric mean ratios (90% confidence intervals [CIs]) for maximum plasma concentration (Cmax) were 1.54 (90% CI 1.26–1.88) and for area under the concentration‐time curve from time 0 to the time of the last measurable concentration (AUCt) were 1.69 (90% CI 1.34–2.14), indicating no clinically significant interaction. DM‐4103 produced no clinically meaningful changes in rosuvastatin or furosemide concentrations, indicating no inhibition at OATP1B1 or OAT3. The BCRP prediction assumed the drug dose is completely soluble in 250 ml; TLV has solubility of ~0.01 g/250 ml. For OATP1B1/OAT3, if fraction unbound for plasma protein binding (PPB) is less than 1%, then 1% is assumed. DM‐4103 has PPB greater than 99.8%. Use of actual drug substance solubility and unbound fraction in plasma would have produced predictions consistent with the clinical results.
Model‐based approach to sampling optimization in studies of antibacterial drugs for infants and young children
Authors: Orito Yuji , Kakara Makoto , Okada Akira , Nagai Naomi 
Published: March 2021

AbstractClinical trials for pediatric indications and new pediatric drugs face challenges, including the limited blood volume due to the patients’ small bodies. In Japan, the Evaluation Committee on Unapproved or Off‐labeled Drugs with High Medical Needs has discussed the necessity of pediatric indications against the background of a lack of Japanese pediatric data. The limited treatment options regarding antibiotics for pediatric patients are associated with the emergence of antibiotic‐resistant bacteria. Regulatory guidelines promote the use of model‐based drug development to reduce practical and ethical constraints for pediatric patients. Sampling optimization is one of the key study designs for pediatric drug development. In this simulation study, we evaluated the precision of the empirical Bayes estimates of pharmacokinetic (PK) parameters based on the sampling times optimized by published pediatric population PK models. We selected three previous PK studies of cefepime and ciprofloxacin in infants and young children as paradigms. The number of sampling times was reduced from original full sampling times to two to four sampling times based on the Fisher information matrix. We observed that the precision of empirical Bayes estimates of the key PK parameters and the predicted efficacy based on the reduced sampling times were generally comparable to those based on the original full sampling times. The model‐based approach to sampling optimization provided a maximization of PK information with a minimum burden on infants and young children for the future development of pediatric drugs.
Application of MCAT questions as a testing tool and evaluation metric for knowledge graph–based reasoning systems
Authors: Fecho Karamarie , Balhoff James , Bizon Chris , Byrd William E. , Hang Sui , Koslicki David , Rensi Stefano E. , Schmitt Patrick L. , Wawer Mathias J. , Williams Mark , Ahalt Stanley C. 
Published: March 2021

Abstract“Knowledge graphs” (KGs) have become a common approach for representing biomedical knowledge. In a KG, multiple biomedical data sets can be linked together as a graph representation, with nodes representing entities, such as “chemical substance” or “genes,” and edges representing predicates, such as “causes” or “treats.” Reasoning and inference algorithms can then be applied to the KG and used to generate new knowledge. We developed three KG‐based question‐answering systems as part of the Biomedical Data Translator program. These systems are typically tested and evaluated using traditional software engineering tools and approaches. In this study, we explored a team‐based approach to test and evaluate the prototype “Translator Reasoners” through the application of Medical College Admission Test (MCAT) questions. Specifically, we describe three “hackathons,” in which the developers of each of the three systems worked together with a moderator to determine whether the applications could be used to solve MCAT questions. The results demonstrate progressive improvement in system performance, with 0% (0/5) correct answers during the first hackathon, 75% (3/4) correct during the second hackathon, and 100% (5/5) correct during the final hackathon. We discuss the technical and sociologic lessons learned and conclude that MCAT questions can be applied successfully in the context of moderated hackathons to test and evaluate prototype KG‐based question‐answering systems, identify gaps in current capabilities, and improve performance. Finally, we highlight several published clinical and translational science applications of the Translator Reasoners.
Optimizing clinical phenotyping to better delineate the complex relationship between type 2 diabetes and Alzheimer’s disease
Authors: Hanson Angela J. , Rubinow Katya B. 
Published: March 2021

AbstractAlzheimer’s disease (AD) is the most common form of dementia, and its prevalence is increasing rapidly. According to the Alzheimer’s Association, over 5 million adults in the United States over the age of 65 years currently have AD, and this number is expected to exceed 13 million by 2050 in the absence of novel, preventative strategies. Epidemiologic studies have implicated the presence of type 2 diabetes mellitus (T2DM) specifically at midlife as a key modifiable risk factor for AD, and AD may increase risk of dysglycemia and T2DM. However, data have been inconsistent with regard to the magnitude of AD risk attributable to T2DM, and the pathways underlying this apparent relationship remain poorly understood. Elucidating the impact of T2DM on AD risk and progression requires greater attention to the myriad facets of T2DM pathophysiology, its comorbid conditions, and attendant treatment modalities, all of which may differentially impact the relationships among T2DM, cognitive decline, and AD. This mini‐review will summarize the discrete facets of T2DM that may influence AD risk and highlight the importance of careful clinical phenotyping in both epidemiologic and interventional studies to better delineate the key pathways and mechanisms linking T2DM and AD.