bluuebunny/crossref_metadata_2025_split huggingface dataset:
LncRNA SNHG1 contributes to the regulation of acute myeloid leukemia cell growth by modulating miR‐489‐3p/SOX12/Wnt/β‐catenin signaling
Authors: Li Chengliang , Gao Qiuying , Wang Minjuan , Xin Hong 
Published: June 2020

AbstractThe long noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) is a critical regulator for the development and progression of multiple tumors. Yet, the role of SNHG1 in acute myeloid leukemia (AML) is unknown. The present study demonstrated that SNHG1 expression was upregulated in AML. SNHG1 silencing markedly repressed AML cell growth, whereas SNHG1 overexpression had the opposite effect. MicroRNA‐489‐3p (miR‐489‐3p) was identified as a SNHG1‐targeting miRNA. SNHG1 knockdown increased miR‐489‐3p expression. Low expression of miR‐489‐3p was correlated with high expression of SNHG1 in AML tissues. miR‐489‐3p overexpression restricted AML cell growth, and SRY‐related high‐mobility‐group box 12 (SOX12) was identified as a miR‐489‐3p‐targeting gene. SNHG1 inhibition or miR‐489‐3p overexpression inactivated Wnt/β‐catenin signaling through downregulation of SOX12. SOX12 overexpression partially reversed the SNHG1 knockdown‐ or miR‐489‐3p overexpression‐mediated effects. Taken together, these data indicate that suppression of SNHG1 downregulates AML cell growth by inactivating SOX12/Wnt/β‐catenin signaling via upregulating miR‐489‐3p.
Application of Physiologically Based Pharmacokinetic Modeling to Predict Drug Exposure and Support Dosing Recommendations for Potential Drug‐Drug Interactions or in Special Populations: An Example Using Tofacitinib
Authors: Tse Susanna , Dowty Martin E. , Menon Sujatha , Gupta Pankaj , Krishnaswami Sriram 
Published: June 2020

AbstractTofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis. It is eliminated via multiple pathways including oxidative metabolism (∼70%) and renal excretion (29%). This study aimed to predict the impact of drug‐drug interactions and renal or hepatic impairment on tofacitinib pharmacokinetics using a physiologically based pharmacokinetic (PBPK) model. The model was developed using Simcyp based on the physicochemical properties and in vitro and in vivo pharmacokinetics data for tofacitinib. The model was verified by comparing the predicted pharmacokinetic profiles with those observed in available clinical studies after single or multiple doses of tofacitinib, as well as with tofacitinib as a victim of drug‐drug interactions (because of inhibition of cytochrome P450 [CYP450] 3A4, CYP450 2C19, or CYP450 induction). In general, good agreement was observed between Simcyp predictions and clinical data. The results from this study provide confidence in using the PBPK modeling and simulation approach to predict the pharmacokinetics of tofacitinib under intrinsic (eg, renal or hepatic impairment) or extrinsic (eg, inhibition of CYP450 enzymes and/or renal transporters) conditions. This approach may also be useful in predicting pharmacokinetics under untested or complex situations (eg, when a combination of intrinsic and extrinsic factors may impact pharmacokinetics) when conducting clinical studies may be difficult, in response to health authority questions regarding dosing in special populations, or for labeling discussions.
Using taurine to increase mesopores in Ce‐based metal–organic framework for enhancing the production of 5‐hydroxymethylfurfural and 5‐ethoxymethylfurfural from fructose
Authors: Wang Chenyu , Li Ke , Ji Peijun 
Published: June 2020

AbstractBACKGROUND5‐hydroxymethylfurfural (HMF) and 5‐ethoxymethylfurfural (EMF) are biomass‐based value‐added chemicals. Various catalytic systems have been studied for converting fructose into HMF and EMF. A more efficient and stable solid acid catalyst is highly desirable for the conversion process.RESULTSIn this study, a novel taurine‐involved Ce metal organic framework material (T‐CeMOF) was synthesized by coordinating Ce to 1,3,5‐benzenetricarboxylic acid (BTC) in the presence of taurine. T‐CeMOF was analyzed with Fourier‐transform infrared (FTIR) spectroscopy, transmission electron microscoy (TEM), and nitrogen adsorption–desorption analysis. Results showed that the presence of taurine makes T‐CeMOF have a much larger specific pore volume than Ce based metal‐organic framwork (CeMOF), which was synthesized by coordinating Ce with the ligand BTC in absence of taurine. It is implied that T‐CeMOF has many more swinging carboxyl groups on the surface than CeMOF. In addition, the sulfonic acid group of taurine is introduced into T‐CeMOF. All of these contribute toward making sure that T‐CeMOF is effective for the conversion of fructose to HMF and EMF in ethanol. Under the catalysis of T‐CeMOF, the total yield of HMF and EMF reached 78.4% within 1 h. T‐CeMOF could be recycled and the catalytic activity of the catalyst was maintained after five cycles.CONCLUSIONT‐CeMOF can be synthesized at room temperature and it achieved a high total yield of HMF and EMF in ethanol within 1 h. T‐CeMOF opens a new route for one‐pot conversion of abundant and cheap fructose‐based biomass into promising biochemicals. © 2020 Society of Chemical Industry (SCI)
Evolutionary sequences in mammalian reproductive biology
Authors: Hunter Ronald H. F. , López‐Gatius Fernando 
Published: June 2020

AbstractBroad biological aspects and accepted evolutionary sequences may offer useful guidance towards a comprehensive explanation of the function of mammalian ovaries and oviducts and their vital contribution to the events of fertilization. Cooling of the preovulatory follicles before ovulation may well have its roots in the primitive stages of external fertilization in which aggregates of oocytes are shed into freshwater.
Fractionated small cell‐free DNA increases possibility to detect cancer‐related gene mutations in advanced colorectal cancer
Authors: Ishida Yasuaki , Takano Shinichi , Maekawa Shinya , Yamaguchi Tatsuya , Yoshida Takashi , Kobayashi Shoji , Iwamoto Fumihiko , Kuno Toru , Hayakawa Hiroshi , Matsuda Shuya , Fukasawa Mitsuharu , Shindo Hiroko , Inoue Taisuke , Nakayama Yasuhiro , Ichikawa Daisuke , Sato Tadashi , Enomoto Nobuyuki 
Published: June 2020

AbstractBackground and AimLiquid biopsy is a method that can efficiently detect tumor genetic abnormalities from body fluids such as blood and urine. Detection sensitivity and the available number of mutations in cell‐free DNA (cfDNA) are limited. In this study, we develop a highly sensitive and comprehensive method to detect mutations from cfDNA by concentrating tumor fractions of small cfDNA in advanced colorectal cancers.MethodsBiopsied specimens and 37 serum samples were collected from 27 patients with advanced colorectal carcinoma. A serum‐extracted cfDNA was divided into enriched fractionated small cfDNA and unfractionated cfDNA. Both cfDNAs were subjected to digital polymerase chain reaction (PCR) to evaluate their KRAS, BRAF, CDKN2A, and TP53 status. Consequently, their mutant allele frequencies (MAFs) were compared and analyzed by next‐generation sequencing (NGS) in conjunction with tissue‐derived DNA.ResultsNGS analyses revealed mutations in TP53 (63%), KRAS (63%), APC (30%), and PIK3CA (22%). Digital PCR could detect mutations in 25 of 27 samples (93%) of unfractionated cfDNA, a rate that increased to 100% when samples were enriched with fractionated small cfDNA (6.8 vs 10.7%, P < 0.001). NGS also showed increased MAFs in fractionated small cfDNA compared to unfractionated cfDNA (16.3 vs 18.8%, P = 0.012) and a tendency to detect a greater number of cancer‐related genes in fractionated cfDNA.ConclusionsFractionated small cfDNA increased MAFs of gene mutations and increases the possibilities to detect cancer‐related genes even in advanced cancer patients from whom it is difficult to obtain tissue samples.
Regioselective aza‐Michael additions of 2‐arylidene‐1,3‐diphenylpropan‐1,3‐diones with isatins: Synthesis of N‐diketone‐functionalized isatins
Authors: Cheng Ya , Li Zheng 
Published: June 2020

AbstractThe efficient aza‐Michael additions of isatins to 2‐arylidene‐1,3‐diphenylpropan‐1,3‐diones at room temperature in the presence of cesium carbonate are described. The salient features of this protocol are no transition‐metal catalysts, mild conditions, high regioselectivity, high atom economy, satisfactory yield and simple work‐up procedures.
An implementation study of oral and blood‐based HIV self‐testing and linkage to care among men in rural and peri‐urban KwaZulu‐Natal, South Africa
Authors: Shapiro Adrienne E , van Heerden Alastair , Krows Meighan , Sausi Kombi , Sithole Nsika , Schaafsma Torin T , Koole Olivier , van Rooyen Heidi , Celum Connie L , Barnabas Ruanne V 
Published: June 2020

AbstractIntroductionIn South Africa, HIV‐infected men are less likely than women to test and know their status (the first UNAIDS “90‐90‐90” target), and men have worse outcomes across the HIV care cascade. HIV self‐testing (HIVST) may address this testing disparity but questions remain over the most effective distribution strategy and linkage following a positive test result. We implemented a men‐focused HIVST distribution programme to evaluate components contributing to participation and retention.MethodsWe conducted an implementation study of multi‐venue HIVST kit distribution in rural and peri‐urban KwaZulu‐Natal (KZN), South Africa. We distributed HIVST kits at community points, workplaces and social venues for on site or take‐home use. Clients could choose blood‐based or oral‐fluid‐based HIVST kits and elect to watch an in‐person or video demonstration. We provided a USD2 incentive to facilitate reporting test results by phone or SMS. Persons with reactive HIVST results were provided immediate confirmatory tests (if used HIVST on site) or were referred for confirmatory testing (if took HIVST off site) and linkage to care for ART initiation. We describe the testing and linkage cascade in this sample and describe predictors of reactive HIVST results and linkage.ResultsBetween July and November 2018, we distributed 4496 HIVST kits in two regions of KZN (96% to men, median age 28 (IQR 23 to 35). Most participants (58%) chose blood‐based HIVST and 42% chose oral‐swab kits. 11% of men were testing for the first time. A total of 3902 (83%) of testers reported their test result to the study team, with 314 (8%) screening positive for HIV. Among 274 men with reactive HIVST results, 68% linked to ART; no significant predictors of linkage were identified. 10% of kit users reported they would prefer a different type (oral vs. blood) of kit for repeat testing than the type they used.ConclusionsHIVST is acceptable to men and rapid distribution with optional testing support is feasible in rural and peri‐urban settings. HIVST kits successfully reached younger men and identified undetected infections. Both oral and blood‐based HIVST were selected. Scaling up HIVST distribution and guidance may increase the number of first‐time testers among men and help achieve the first UNAIDS “90” for men in South Africa.
Male partner testing and sexual behaviour following provision of multiple HIV self‐tests to Kenyan women at higher risk of HIV infection in a cluster randomized trial
Authors: Napierala Sue , Bair Elizabeth F , Marcus Noora , Ochwal Perez , Maman Suzanne , Agot Kawango , Thirumurthy Harsha 
Published: June 2020

AbstractIntroductionWithout significant increases in uptake of HIV testing among men, it will be difficult to reduce HIV incidence to disease elimination levels. Secondary distribution of HIV self‐tests by women to their male partners is a promising approach for increasing male testing that is being implemented in several countries. Here, we examine male partner and couples testing outcomes and sexual decision making associated with this approach in a cluster randomized trial.MethodsWe examined data from women at higher risk of HIV participating in the intervention arm of an ongoing pair‐matched cluster randomized trial in Kenya. HIV‐negative women ≥18 years who self‐reported ≥2 partners in the past month were eligible. Participants received self‐tests at enrolment and three‐monthly intervals. They were encouraged to offer tests to sexual partners with whom they anticipated condomless sex. At six months, we collected data on self‐test distribution, male partner and couples testing, and testing and sexual behaviour in the three most recent transactional sex encounters. We used descriptive analyses and generalized estimating equation models to understand how sexual behaviour was influenced by self‐test distribution.ResultsFrom January 2018 to April 2019, 921/1057 (87%) participants completed six‐month follow‐up. Average age was 28 years, 65% were married, and 72% reported income through sex work. Participants received 7283 self‐tests over six months, a median of eight per participant. Participants offered a median three self‐tests to sexual partners. Of participants with a primary partner, 94% offered them a self‐test. Of these, 97% accepted the test. When accepted, couples testing was reported among 91% of participants. Among 1954 transactional sex encounters, 64% included an offer to self‐test. When offered self‐tests were accepted by 93% of partners, and 84% who accepted conducted couples testing. Compared to partners with an HIV‐negative result, condom use was higher when men had a reactive result (56.3% vs. 89.7%, p < 0.01), were not offered a self‐test (56.3% vs. 62.0%, p = 0.02), or refused to self‐test (56.3% vs. 78.3, p < 0.01).ConclusionsProviding women with multiple self‐tests facilitated male partner and couples testing, and led to safer sexual behaviour. These findings suggest secondary distribution is a promising approach for reaching men and has HIV prevention potential.Clinical Trial Number: NCT03135067.
Creating HIV risk profiles for men in South Africa: a latent class approach using cross‐sectional survey data
Authors: Gottert Ann , Pulerwitz Julie , Heck Craig J , Cawood Cherie , Mathur Sanyukta 
Published: June 2020

AbstractIntroductionEngaging at‐risk men in HIV prevention programs and services is a current priority, yet there are few effective ways to identify which men are at highest risk or how to best reach them. In this study we generated multi‐factor profiles of HIV acquisition/transmission risk for men in Durban, South Africa, to help inform targeted programming and service delivery.MethodsData come from surveys with 947 men ages 20 to 40 conducted in two informal settlements from May to September 2017. Using latent class analysis (LCA), which detects a small set of underlying groups based on multiple dimensions, we identified classes based on nine HIV risk factors and socio‐demographic characteristics. We then compared HIV service use between the classes.ResultsWe identified four latent classes, with good model fit statistics. Theolder high‐risk class(20% of the sample; mean age 36) were more likely married/cohabiting and employed, with multiple sexual partners, substantial age‐disparity with partners (eight years younger on‐average), transactional relationships (including more resource‐intensive forms like paying for partner’s rent), and hazardous drinking. Theyounger high‐risk class(24%; mean age 27) were likely unmarried and employed, with the highest probability of multiple partners in the last year (including 42% with 5+ partners), transactional relationships (less resource‐intensive, e.g., clothes/transportation), hazardous drinking, and inequitable gender views. Theyounger moderate‐risk class(36%; mean age 23) were most likely unmarried, unemployed technical college/university students/graduates. They had a relatively high probability of multiple partners and transactional relationships (less resource‐intensive), and moderate hazardous drinking. Finally, theolder low‐risk class(20%; mean age 29) were more likely married/cohabiting, employed, and highly gender‐equitable, with few partners and limited transactional relationships. Circumcision (status) was higher among the younger moderate‐risk class than either high‐risk class (p < 0.001). HIV testing and treatment literacy score were suboptimal and did not differ across classes.ConclusionsDistinct HIV risk profiles among men were identified. Interventions should focus on reaching the highest‐risk profiles who, despite their elevated risk, were less or no more likely than the lower‐risk to use HIV services. By enabling a more synergistic understanding of subgroups, LCA has potential to enable more strategic, data‐driven programming and evaluation.
Lottery incentives have short‐term impact on ART initiation among men: results from a randomized pilot study
Authors: Barnabas Ruanne V , van Heerden Alastair , McConnell Margaret , Szpiro Adam A , Krows Meighan L , Schaafsma Torin T , Ngubane Thulani , Nxele Rose B , Joseph Philip , Baeten Jared M , Celum Connie L , van Rooyen Heidi 
Published: June 2020

AbstractIntroductionAmong people living with HIV in South Africa, viral suppression is lower among men than women. The study aim was to test the impact of lottery incentives, which reward positive health choice (e.g. antiretroviral therapy (ART) linkage) with a chance to win a prize, on strengthening the HIV care continuum including ART initiation and viral suppression for men.MethodsWe conducted a randomized, prospective trial of lottery incentives in the context of HIV testing and linkage to ART in rural KwaZulu‐Natal, South Africa. Men living with HIV were randomly allocated to: lottery incentives and motivational text messages or motivational text messages only. Lottery prize eligibility was conditional on clinic registration, ART initiation, or viral suppression by one, three and six months respectively. After completing each continuum step, participants in the lottery group were notified whether they had won and were encouraged to continue in care. Lottery prizes were either a mobile phone, data or a gift card (valued at R1000/$100). Kaplan–Meier curves were plotted to determine time to ART initiation by study group. The primary outcome was viral suppression at six months.ResultsBetween November 2017 and December 2018, we tested 740 men for HIV and enrolled 131 HIV‐positive men who reported not being on ART. At baseline, 100 (76%) participants were 30 years and older, 95 (73%) were unemployed and the median CD4 count was 472 cells/μL. At study exit, 84% (110/131) of participants had visited a clinic and 62% (81/131) were virally suppressed. Compared to motivational text messages, lottery incentives decreased the median time to ART initiation from 126 to 66 days (p = 0.0043, age‐adjusted Cox regression) among all participants, and, from 134 days to 20 days (p = 0.0077) among participants who were not virally suppressed at baseline. Lottery incentives had an inconclusive effect on clinic registration (RR = 1.21, 95% CI: 0.83 to 1.76) and on viral suppression at six months (RR = 1.13, 95% CI: 0.73 to 1.75) compared to motivational text messages.ConclusionsConditional lottery incentives shortened the time to ART initiation among South African men. Behavioural economics strategies strengthen linkage to ART, but the study power was limited to see an impact on viral suppression.Clinical Trial NumberNCT03808194.
Comparative forelimb morphology of scratch‐digging and chisel‐tooth digging African mole‐rat species
Authors: Doubell Narusa S. , Sahd Lauren , Kotzé Sanet H. 
Published: June 2020

AbstractBathyergus suillus (Cape dune mole‐rat) and Heterocephalus glaber (naked mole‐rat) are two species of subterranean burrowing rodents. Bathyergus suillus occurs in soft sandy soils and is regarded as a scratch‐digger, while H. glaber is found in hard, compact soils and is a chisel‐tooth digging species. The present study aimed to determine musculoskeletal differences in the forelimb of these two species. The muscles of the forelimb, back and neck were dissected to the points of origin and insertion in the left and right forelimbs, B. suillus (n = 7) and H. glaber (n = 5). Dissected muscles were photographed before maceration to demonstrate muscle attachments. The scapular spine, acromion process and clavicle were relatively straight in B. suillus. In comparison a curved scapular spine, acromion process and clavicle were observed in H. glaber. In both species, the clavicle rested on the greater tuberosity of the humerus. In B. suillus, the deltoid tuberosity was prominent and situated more distally on the humeral shaft compared to the indistinct, more proximally situated deltoid tuberosity in H. glaber. A prominent bony structure underlying the thenar pad as well as a cartilaginous protrusion beneath the hypothenar pad were observed on the palmar surface of the manus in B. suillus. Prominent claws were observed in B. suillus. A robust m. sternohyoideus was observed in H. glaber while mm. tensor fasciae antebrachii and coracobrachialis were absent. The flexors of the antebrachium of B. suillus had additional and enlarged attachment sites. The forelimb of B. suillus may be morphologically adapted for scratch‐digging with relatively large and additional forelimb muscles and robust bones. In comparison, H. glaber had a reduction in the relative size, amount of muscles as well as number of attachment sites in the forelimb muscles, while the well‐developed ventral neck muscles may facilitate neck and head stabilisation during chisel‐tooth digging.
Gold and silver nanoparticles‐based laser desorption/ionization mass spectrometry method for detection and quantification of carboxylic acids
Authors: Kołodziej Artur , Ruman Tomasz , Nizioł Joanna 
Published: June 2020

AbstractA comparison of ionization efficiency for gold and silver nanoparticles used as an active media of matrix‐less laser desorption/ionization (LDI) mass spectrometry (MS) methods was made for carboxylic acids including fatty acids. The matrix‐assisted laser desorption/ionization (MALDI)‐type targets containing monoisotopic cationic 109Ag nanoparticles (109AgNPs) and Au nanoparticles (AuNPs) were used for rapid MS measurements of 10 carboxylic acids of different chemical properties. Carboxylic acids were directly quantified in experiments with 10 000‐fold concentration change conditions ranging from 1 mg/ml to 100 ng/ml which equates to 1 μg to 100 pg of carboxylic acids per measurement spot.
Dissecting the potential role of hepatitis E virus ORF1 nonstructural gene in cross‐species infection by using intergenotypic chimeric viruses
Authors: Tian Debin , Yugo Danielle M. , Kenney Scott P. , Lynn Heffron C. , Opriessnig Tanja , Karuppannan Anbu K. , Bayne Jenna , Halbur Patrick G. , Meng Xiang‐Jin 
Published: June 2020

AbstractHepatitis E virus (HEV) infects humans and more than a dozen other animal species. We previously showed that open reading frame 2 (ORF2) and ORF3 are apparently not involved in HEV cross‐species infection, which infers that the ORF1 may contribute to host tropism. In this study, we utilize the genomic backbone of HEV‐1 which only infects humans to construct a panel of intergenotypic chimeras in which the entire ORF1 gene or its functional domains were swapped with the corresponding regions from HEV‐3 that infects both humans and pigs. We demonstrated that the chimeric HEVs were replication competent in human liver cells. Subsequently, we intrahepatically inoculated the RNA transcripts of chimeras into pigs to determine if the swapped ORF1 regions confer the chimeras’ ability to infect pigs. We showed that there was no evidence of infectivity in pigs for any of the chimeras. We also investigated the role of human ribosome protein sequence S17, which expanded host range in cultured cells, in HEV cross‐species infection. We demonstrated that S17 insertion in HEV ORF1 did not abolish HEV replication competency in vitro, but also did not expand HEV host tropism in vivo. The results highlight the complexity of the underlying mechanism of HEV cross‐species infection.