bluuebunny/crossref_metadata_2025 huggingface dataset:
“When I got the news”: Aboriginal fathers in the Kimberley region yarning about their experience of the antenatal period
Authors: Carlin Emma , Cox Zaccariah , Spry Erica , Monahan Conor , Marley Julia V. , Atkinson David
Published: June 2020

Issue addressed

Paternal involvement during the antenatal period is recognised as a positive contributor to a child's health and developmental outcomes. Little is known about Aboriginal Australian men's experiences and perceptions during their partner's antenatal period.

Methods

A qualitative yarning methodology was used to explore the experiences of ten Aboriginal Australian fathers during their partner's antenatal period, in a remote Northern Australian town.

Results

The study found the participants valued supporting their partners through pregnancy, making positive changes to their lifestyles, and having access to information on pregnancy. Participants described experiencing multiple stressors during the antenatal period that impacted on their social and emotional wellbeing. This is despite the range of protective factors identified by them. Participants had diverse experiences with health care providers during the antenatal period.

Conclusions

This study demonstrated that these Aboriginal men valued engagement with antenatal care (ANC) services and highlighted strategies to improve Aboriginal paternal involvement with ANC services.

So what?

Enhancing ANC to be inclusive of fathers, through a local co‐design process, could strengthen and support Aboriginal families to achieve improved health and wellbeing outcomes across the family system.
A feasibility study of implementing a patient‐centered outcome set for pregnancy and childbirth
Authors: Depla Anne L. , Ernst‐Smelt Hiske E. , Poels Marjolein , Crombag Neeltje M. , Franx Arie , Bekker Mireille N.
Published: June 2020

Background and Aims

Patient‐reported outcome and experience measures (PROM and PREM) can facilitate shared decision making and hold potential to improve healthcare quality. However, their adoption in perinatal care is still limited. The International Consortium for Health Outcomes Measurement (ICHOM) developed a Pregnancy and Childbirth (PCB) outcome set, including PROM and PREM questionnaires. We studied the feasibility to use these PROMs/PREMs in Dutch perinatal care, addressing both women's and professionals' perspective.

Methods

Patients and professionals in primary and hospital care participated. Women under care at one of five timepoints for PROM/PREM collection of the PCB set (2 during pregnancy, 3 postpartum) were e‐mailed a questionnaire and discussed their answers with their obstetric professional the next regular visit. Compliance was recorded. After discussing the PROMs/PREMs, usability and experience were assessed with separate surveys amongst women and professionals.

Results

Of 26 women approached, 21 completed and discussed their PROM/PREM questionnaire. Mean questionnaire completion rate was 97%. Average reported time completing the questionnaires was 10 minutes; most women (90%) stated this was acceptable. Women preferred completing questionnaires digitally and discuss their answers with an obstetric professional rather than other care professionals, also 6 months postpartum. Over half of women agreed PROMs/PREMs supported shared decision making (58%), ability to raise issues (60%), and patient‐clinician relationship (52%). Six professionals participated: two obstetricians, two clinical midwives, and two community midwives. Most professionals experienced sufficient time to discuss the responses, except at 6 months postpartum. They knew what items to discuss but did not always feel responsible to act upon them. Professionals agreed PROMs/PREMs supported symptom detection and personalized care.

Conclusions

Patients and obstetric professionals consider the PCB set a feasible instrument for PROM/PREM assessment, with good compliance, acceptability and usability. Important determinants of successful implementation are a well‐equipped ICT‐tool, agreements regarding professionals' responsibilities and how outcomes are discussed or acted upon.
Automated diagnosis system for age‐related macular degeneration using hybrid features set from fundus images
Authors: Khalid Samina , Akram Muhammad Usman , Shehryar Tehmina , Ahmed Waqas , Sadiq Marium , Manzoor Mahak , Nosheen Nelam
Published: June 2020

Impairment to macula can cause loss of central vision. There are various macular disorders that can affect macular region and if not treated at an early stage can cause irreversible central vision loss. Age‐related macular degeneration (AMD) disorder is one of the most threading macular disorder. Bright lesion, drusens presence in macular region is known as the hallmark of AMD disorder. This bright lesion differentiation from other bright lesion like exudates is important for accurate diagnosis of AMD. Focus of this article is automated diagnosis of affected macular region by applying a hybrid features set containing textural, color, and structural/shape features for more accurate detection of AMD at an early stage using fundus images. These features also help to distinguish drusens from exudates. The proposed algorithm at first stage, detect macular region from input fundus image and then perform features extraction based on textural pattern, edge, and structural properties of macular region to classify abnormal macula from normal macula. For classification, we have used support vector machine (SVM), K‐nearest neighbor and neural networks but SVM classifier achieves high accuracy. The proposed algorithm is tested on publicly available STARE and locally available AFIO datasets. Attained sensitivity, specificity, and accuracy of our proposed system are 97.5%, 95% and 95.45%, respectively, when applied on STARE dataset. When we have applied our proposed system on AFIO dataset, we have attained sensitivity, specificity, and accuracy of 93.3%, 92% and 92.34%, respectively.
Promoting parent–infant responsiveness in families experiencing homelessness
Authors: Herbers Janette E. , Cutuli J. J. , Fugo Perrin B. , Nordeen Elke R. , Hartman Michael J.
Published: June 2020

My Baby's First Teacher is an intervention designed specifically for parents with infants staying in emergency homeless shelters. Infants are overrepresented in shelter populations and face considerable risk to their development, including mental health. We utilized a randomized controlled design across three family shelters to evaluate the program's effectiveness with 24 dyads assigned to the intervention compared to 21 dyads in care‐as‐usual. Dyads were randomized by round at each site to account for shelter effects. We used path analysis to illustrate change over time and in relation to intervention assignment.
Mother's prenatal and postpartum depression symptoms and infant's sleep problems at 6 months
Authors: Dias Cláudia Castro , Figueiredo Bárbara
Published: June 2020

Mother's prenatal and postpartum depression have been associated with infant's sleep problems. This study aimed to analyze (a) the effects of mother's prenatal and postpartum depression symptoms, including the effects of prenatal and postpartum anxiety and depression scores of the Edinburgh Postnatal Depression Scale (EPDS), on infant's sleep problems at 6 months, and (b) the interaction effect between mother's prenatal and postpartum depression symptoms and infant's sex on infant's sleep problems at 6 months. The sample was comprised of 164 mother–infant dyads whose mothers completed measures of depression at the third trimester of pregnancy, 2 weeks, 3 and 6 months postpartum and a measure of infant's sleep problems at 6 months (CSHQ‐I). Mother's prenatal depression symptoms, specifically depression scores of the EPDS, predicted more infant's sleep anxiety and daytime sleepiness, while mother's depression symptoms at 2 weeks postpartum, specifically anxiety scores of the EPDS, predicted more bedtime resistance and CSHQ‐I total scores at 6 months. Boys of mothers with more prenatal depression symptoms presented more sleep anxiety at 6 months. Both mother's prenatal and early postpartum depression symptoms have a negative effect on the emergence of infant's sleep problems. Additionally, boys seem more vulnerable to mother's prenatal depression symptoms.
Nuclear factor erythroid 2 (NF‐E2) p45‐related factor 2 interferes with homeodomain‐interacting protein kinase 2/p53 activity to impair solid tumors chemosensitivity
Authors: D'Orazi Gabriella , Garufi Alessia , Cirone Mara
Published: June 2020

Resistance to chemotherapy represents a major hurdle to successful cancer treatment. A key role for efficient response to anticancer therapies is played by TP53 oncosuppressor gene that indeed is mutated in 50% of human cancers or inactivated at protein level in the remaining 50%. Homeodomain‐interacting protein kinase 2 (HIPK2) is the wild‐type p53 (wtp53) apoptotic activator, and its inhibition by hypoxia or hyperglycemia may contribute to tumor chemoresistance mainly by impairing p53 apoptotic activity. Another important molecule able to induce chemoresistance is nuclear factor erythroid 2 (NF‐E2) p45‐related factor 2 (NRF2) transcription factor, whose activation by oxidative and/or electrophilic stress regulates a transcriptional antioxidant program allowing cancer cells to adapt and survive to stresses. NRF2 may shift from cytoprotective to tumor‐promoting function, according to tumor phases. NRF2 may crosstalk with both wtp53 and mutant p53 (mutp53), inhibiting the wtp53 apoptotic function and strengthening the mutp53 oncogenic function. NRF2 has also been shown to induce HIPK2 mRNA expression cooperating in inducing cytoprotection. Although HIPK2, p53, and NRF2 have been individually extensively studied, their interplay has not been clearly addressed yet. On the basis of the background and our results, we aim at hypothesizing the unexpected pro‐survival activity played by the NRF2/HIPK2/p53 interplay that can be hijacked by cancer cells to bypass drugs cytotoxicity.
Effects of genetic variations in Acads gene on the risk of chronic obstructive pulmonary disease
Authors: Yuan Yiming , Yang Shanshan , Deng Dan , Chen Yulong , Zhang Caixia , Zhou Ruixue , Su Zhiguang
Published: June 2020

Short‐chain acyl‐CoA dehydrogenase (SCAD), encoded by the Acads gene, functions in the mitochondrial β‐oxidation of saturated short‐chain fatty acids. SCAD deficiency results in mitochondrial dysfunction, which is one underlying biological mechanism of chronic obstructive pulmonary disease (COPD) pathogenesis. In this case–control study, we aimed to examine the effects of Acads gene polymorphisms on the susceptibility to COPD. A total of 16 tagging single‐nucleotide polymorphisms (SNPs) in Acads gene region was identified and genotyped in 646 unrelated ethnic Chinese Han individuals including 279 patients with COPD and 367 healthy controls, their allelic and genotypic associations with COPD were determined by different genetic models. Furthermore, we estimated the linkage disequilibrium and haplotypes from these tested variants and determined the effects of haplotypes on the risk of COPD. The allelic and genotypic frequencies of SNPs rs2239686 and rs487915 in Acads gene were significantly different between COPD patients and controls, no statistically significant results were observed for other SNPs. Minor alleles A of rs2239686 and T of rs487915 were associated with a decreased pulmonary function and an increased COPD risk in a dominant manner. Functional analysis indicated that the risk allele A of rs2239686 could increase Acads expressions and the intracellular reactive oxygen species content. Haplotype analysis revealed that the haplotypes CTCCT in block 2 (rs3794216‐rs3794215‐rs34491494‐rs558314‐rs7312316) as well as GC in block 3 (rs2239686‐rs487915) were protective against COPD, while haplotypes CTCGC in block 2 and AT in block 3 exhibited significant associations with the increased susceptibility to COPD. Our results suggest that Acads gene could potentially be a risk factor of COPD and thus its genetic variants might be as genetic biomarkers to predict the COPD susceptibility.
Initial outcomes of an augmented competing stimulus assessment
Authors: Hagopian Louis P. , Frank‐Crawford Michelle A. , Javed Noor , Fisher Alyssa B. , Dillon Christopher M. , Zarcone Jennifer R. , Rooker Griffin W.
Published: June 2020

Competing stimulus assessments (CSAs) are designed to identify stimuli that, when made freely available, reduce problem behavior. Although CSAs have demonstrated utility, identifying competing stimuli can be difficult for some individuals. The current study describes outcomes from an augmented CSA (A‐CSA) for 6 consecutively encountered cases with treatment‐resistant subtypes of automatically maintained problem behavior. When test stimuli were made freely available, only between 0 and 1 effective competing stimuli were identified for each case. Prompting and response blocking were temporarily employed in succession to promote engagement with stimuli and disrupt problem behavior. When those procedures were withdrawn and stimuli made freely available, the number of effective competing stimuli increased in all 6 cases. Findings suggest that procedures designed to promote engagement and disrupt problem behavior may allow the A‐CSA to be a platform not only for identifying competing stimuli, but also for actively establishing competing stimuli.
Potential damage in pulmonary arterial hypertension: An experimental study of pressure‐induced damage of pulmonary artery
Authors: Wang Yuheng , Gharahi Hamidreza , Grobbel Marissa R. , Rao Akshay , Roccabianca Sara , Baek Seungik
Published: June 2020

Pulmonary arterial hypertension (PAH) is associated with elevated pulmonary arterial pressure. PAH prognosis remains poor with a 15% mortality rate within 1 year, even with modern clinical management. Previous clinical studies proposed wall shear stress (WSS) to be an important hemodynamic factor affecting cell mechanotransduction, growth and remodeling, and disease progress in PAH. However, WSS in vivo is typically at most 2.5 Pa and a doubt has been cast whether WSS alone can drive disease progress. Furthermore, our current understanding of PAH pathology largely comes from small animals' studies in which caliber enlargement, a hallmark of PAH in humans, is rarely reported. Therefore, a large‐animal experiment on pulmonary arteries (PAs) is needed to validate whether increased pressure can induce enlargement of PAs caliber. In this study, we use an inflation testing device to characterize the mechanical behavior, both nonlinear elastic behavior and irreversible damage of porcine arteries. The parameters of elastic behavior are estimated from the inflation test at a low‐pressure range before and after over‐pressurization. Then, histological images are qualitatively examined for medial and adventitial layers. This study sheds light on the relevance of pressure‐induced damage mechanism in human PAH.
Effects of metformin and pioglitazone combination on apoptosis and AMPK/mTOR signaling pathway in human anaplastic thyroid cancer cells
Authors: Ozdemir Kutbay Nilufer , Biray Avci Cigir , Sarer Yurekli Banu , Caliskan Kurt Cansu , Shademan Behrouz , Gunduz Cumhur , Erdogan Mehmet
Published: June 2020

Anaplastic cancer constitutes 1% of thyroid cancers, and it is one of the most aggressive cancers. Treatment options are external radiation therapy and/or chemotherapy. The success rate with these treatment modalities is not satisfactory. We aimed to evaluate the effects of metformin (MET) and pioglitazone (PIO) combination on apoptosis and AMP‐activated protein kinase/mammalian target of rapamycin (mTOR) signaling pathway in human anaplastic thyroid cancer cells. In this study, we evaluated the effects of MET and PIO individually and the combination of the two drugs on the cellular lines SW1736 and C643 ATC. Genes contained in the mTOR signaling pathway were examined using human mTOR Signalization RT2 Profiler PCR Array. In C643 and SW1736 cell lines, IC50 doses of MET and PIO were found out as 17.69 mM, 11.64 mM, 27.12 µM, and 23.17 µM. Also, the combination of MET and PIO was determined as an additive according to isobologram analyses. We have found the downregulation of the expression levels of oncogenic genes: AKT3, CHUK, CDC42, EIF4E, HIF1A, IKBKB, ILK, MTOR, PIK3CA, PIK3CG, PLD1, PRKCA, and RICTOR genes, in the MET and PIO combination‐treated cells. In addition, expression levels of tumor suppressor genes, DDIT4, DDIT4L, EIF4EBP1, EIF4EBP2, FKBP1A, FKBP8, GSK3B, MYO1C, PTEN, ULK1, and ULK2, were found to have increased significantly. The MET + PIO combination was first applied to thyroid cancer cells, and significant reductions in the level of oncogenic genes were detected. The decreases, particularly, in AKT3, DEPTOR, EIF4E, ILK, MTOR, PIK3C, and PRKCA expressions indicate that progression can be prevented in thyroid cancer cells and these genes could be selected as therapeutic targets.
MiR‐10b inhibits migration and invasion of pancreatic ductal adenocarcinoma via regulating E2F7
Authors: Xu Cui , Qi Xiangxiu
Published: June 2020

Background

Abnormal microRNAs (miRNAs) expression is closely related to the development and poor prognosis of pancreatic ductal adenocarcinoma (PDAC). We aimed to elucidate the invasive mechanism and clinical significance of miR‐10b in PDAC.

Methods

The RNA sequence data of pancreatic cancer were extracted from the TCGA database. R packages were performed to analyze the differential expression of RNAs. TargetScan, picTar, and miRanda were used to predict the target gene of miRNA. The expression level of the selected candidate was tested by western blot and RT‐PCR in PDAC cells and tissues. Scrape and Transwell assays were determined the effect of candidate molecules on cell migration and invasion. The gain of function and loss of function was achieved by co‐culture with mimics and vector. Luciferase reporters were generated based on the psiCHECK2 vector. The relative luciferase activity was measured with the Dual‐Luciferase Reporter Assay System and Infinate M200 PRO microplate reader.

Results

Based on the TCGA data and bioinformatics analysis, we obtained seven differentially expressed miRNAs. Both TCGA data and our center clinical date indicated that miR‐10b was contributed to the poor survival of PDAC. Based on the target gene prediction database, we found that E2F7 was a target mRNA of miR‐10b. In subsequent experiments in molecular biology, miR‐10b expression was downregulated in PDAC cells and tissues, while E2F7 was upregulated. Scrape and Transwell assay indicated that miR‐10b could inhibit the invasion and migration of PDAC. MiR‐10b was confirmed to be by the E2F7 targeting site by dual‐luciferase report. Moreover, rescue experiments prove that miR‐10b could inhibit the invasion and migration of PDAC cells by regulating E2F7 expression.

Conclusion

Our results suggest that miR‐10b could inhibit the progression of PDAC by regulating E2F7 expression and acts as an independent prognostic risk factor for PDAC.
Urinary neutrophil gelatinase‐associated lipocalin rapidly decreases in the first week after kidney transplantation
Authors: Wang Yaqi , Jia Yu , Wang Chunyan , Gao Xiaojuan , Liu Yuke , Yue Baohong
Published: June 2020

Background

Recipient delayed graft function, which is defined as dialysis in the first week after transplantation, is one of the most common early complications after kidney transplantation. This study aimed to evaluate the daily changes in renal function‐related biomarkers in the first week post‐transplant.

Methods

A total of 72 kidney transplant recipients were retrospectively included in this study. Clinical and laboratory data were collected daily during the first week post‐transplant, including urinary concentrations of neutrophil gelatinase‐associated lipocalin (NGAL), serum concentrations of NGAL, creatinine, urea nitrogen, uric acid (UA), β2‐microglobulin, cystatin C, and estimated glomerular filtration rate (eGFR).

Results

There were no significant differences in urea nitrogen (P = .375), UA (P = .090), and cystatin C (P = .691), while urinary NGAL (P < .0001), serum NGAL (P < .0001), creatinine (P < .0001), β2‐microglobulin (P < .0001), and eGFR (P < .0001) were statistically significant in the first week post‐transplant. In comparison with serum NGAL (P < .0001), creatinine (P < .0001), β2‐microglobulin (P = .001), and eGFR (P = .001), the change ratios of urinary NGAL changed the most between day 1 and day 2 after renal transplantation, while the changing degree of urinary NGAL showed no significant difference compared with these indicators between day 1 and day 7 after kidney transplantation.

Conclusion

Urinary NGAL is a sensitive marker for indicating renal function. Urinary NGAL combined with other markers can be more helpful for evaluating renal function in the first week following kidney transplantation.
Development of a sensitive HPLC‐MS/MS method for 25‐hydroxyvitamin D2 and D3 measurement in capillary blood
Authors: Jiao XianTing , Yuan Yichun , Wang Xirui , Li Juan , Liu Bin , Yuan Tao , Yu XiaoDan
Published: June 2020

Background

Measurement of 25‐hydroxyvitamin D [25(OH)D)] levels is important. The current method requires a relatively large volume of serum. To minimize the amount of serum needed, we established a high‐performance liquid chromatography‐tandem mass spectrometry (HPLC‐MS/MS) method to measure 25(OH)D in capillary serum.

Methods

Venous blood and fingertip blood were collected from 90 participants. Volumes of 100 µL of venous serum and 20 µL of capillary serum were collected. The serum samples were pretreated by protein removal, extraction and concentration, and an HPLC‐MS/MS method based on chromatographic separation and multi reactive ion monitoring was conducted. The intra‐ and inter‐batch variation coefficients were less than 10% for both 25‐hydroxyvitamin D3[25(OH)D3] and 25‐hydroxyvitamin D2[25(OH)D2)]. For venous specimens, the accuracies were 3.87% and 4.91%, respectively. For capillary specimens, the accuracies were 1.65% and 5.32%, respectively.

Results

The limit of detection (LOD) of 25(OH)D3 was 0.01 ng/mL, and the LOD of 25(OH)D2 was 0.05 ng/mL. The results showed that the mean concentration of 25(OH)D in venous blood was 22.56 ± 9.50 ng/mL, while the mean concentration of 25(OH)D in capillary blood was 18.14 ± 7.86 ng/mL. Furthermore, the adjusted capillary blood 25(OH)D level was 22.99 ± 10.24 ng/mL by the correction formula in our study. Similarly, the mean concentration of 25(OH)D3 in capillary blood was 17.98 ± 7.98 ng/mL. The adjusted capillary blood 25(OH)D3 level was 22.85 ± 10.42 ng/mL. No difference in the content of 25(OH)D or 25(OH)D3 was found between venous serum and corrected capillary serum. The correlation coefficients between venous and corrected capillary concentrations of 25(OH)D and 25(OH)D3 were 0.7941 and 0.8103, respectively, and the areas under the receiver operating characteristic curve were 0.9367 and 0.9565, respectively.

Conclusions

This capillary blood method requires minimal sample preparation and is suitable for routine use in the 25(OH)D detection.
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

The 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

Tofacitinib 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

BACKGROUND

5‐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.

RESULTS

In 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.

CONCLUSION

T‐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

Broad 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

Background and Aim

Liquid 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.

Methods

Biopsied 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.

Results

NGS 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.

Conclusions

Fractionated 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

The 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

Introduction

In 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.

Methods

We 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.

Results

Between 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.

Conclusions

HIVST 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

Introduction

Without 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.

Methods

We 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.

Results

From 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).

Conclusions

Providing 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

Introduction

Engaging 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.

Methods

Data 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.

Results

We 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.

Conclusions

Distinct 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

Introduction

Among 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.

Methods

We 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.

Results

Between 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.

Conclusions

Conditional 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 Number

NCT03808194.
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

Bathyergus 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

A 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

Hepatitis 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.