bluuebunny/crossref_metadata_2025 huggingface dataset:
Drug-target interactions prediction using marginalized denoising model on heterogeneous networks
Authors: Tang Chunyan , Zhong Cheng , Chen Danyang , Wang Jianyi
Published: July 2020

Background

Drugs achieve pharmacological functions by acting on target proteins. Identifying interactions between drugs and target proteins is an essential task in old drug repositioning and new drug discovery. To recommend new drug candidates and reposition existing drugs, computational approaches are commonly adopted. Compared with the wet-lab experiments, the computational approaches have lower cost for drug discovery and provides effective guidance in the subsequent experimental verification. How to integrate different types of biological data and handle the sparsity of drug-target interaction data are still great challenges.

Results

In this paper, we propose a novel drug-target interactions (DTIs) prediction method incorporating marginalized denoising model on heterogeneous networks with association index kernel matrix and latent global association. The experimental results on benchmark datasets and new compiled datasets indicate that compared to other existing methods, our method achieves higher scores of AUC (area under curve of receiver operating characteristic) and larger values of AUPR (area under precision-recall curve).

Conclusions

The performance improvement in our method depends on the association index kernel matrix and the latent global association. The association index kernel matrix calculates the sharing relationship between drugs and targets. The latent global associations address the false positive issue caused by network link sparsity. Our method can provide a useful approach to recommend new drug candidates and reposition existing drugs.
Males of a sexually cannibalistic spider chemically assess relative female quality
Authors: Cory Anna-Lena , Schneider Jutta M.
Published: July 2020

Background

Mate choice is a taxonomically wide-spread phenomenon, mostly exerted by females although male mate choice occurs as well. While costs and benefits of choosiness have been well studied, the underlying mechanisms are largely unclear. Different models exist, namely best-of-n or threshold rules, based on sequential or simultaneous sampling, which differ in the required cognitive demands. We applied an experimental approach to shed light on the underlying mechanisms of male mate choice in the sexually cannibalistic spider Argiope bruennichi. Males are limited to two copulations and preferentially monopolise large females, while they may leave smaller females after a single copulation and resume mate search. Here, we utilised significant size-differences between females from Northern and Southern populations and presented males with three different-sized females that were matched for origin: all three females originated either from the same Northern European population as the males or from Southern populations where the smallest female was about the same size as the largest Northern female. This allowed testing the hypothesis that males base their mating tactic on a fixed local size threshold. We predicted Northern males to be choosy among Northern females, but to accept all Southern females since they would all be above that threshold.

Results

Males copulated with the first female they encountered, which was independent of her body size. Regardless of the females’ origins, males chose a monogynous tactic with the largest female in the trio, while they left the smallest female after one copulation. The same pattern applied to Southern females even though the smallest females in the trio were of a similar size as monopolised Northern females. Since males have poor eyesight and did not actively sample all females, they likely have gained information about relative size differences between females based on volatile chemical cues only.

Conclusions

Our findings suggest that male A. bruennichi can assess relative differences in mate quality and adjust their mating tactic to the prevailing conditions (Northern vs. Southern). We reject the presence of a locally-adapted fixed threshold and argue that our results are best explained by an adjustable threshold that was raised under Southern conditions.
Identification of candidate genes and regulatory factors related to growth rate through hypothalamus transcriptome analyses in broiler chickens
Authors: Piórkowska Katarzyna , Żukowski Kacper , Połtowicz Katarzyna , Nowak Joanna , Ropka-Molik Katarzyna , Derebecka Natalia , Wesoły Joanna , Wojtysiak Dorota
Published: July 2020

Background

Intensive selection for growth rate (GR) in broiler chickens carries negative after-effects, such as aberrations in skeletal development and the immune system, heart failure, and deterioration of meat quality. In Poland, fast-growing chicken populations are highly non-uniform in term of growth rate, which is highly unprofitable for poultry producers. Therefore, the identification of genetic markers for boiler GR that could support the selection process is needed. The hypothalamus is strongly associated with growth regulation by inducing important pituitary hormones. Therefore, the present study used this tissue to pinpoint genes involved in chicken growth control.

Results

The experiment included male broilers of Ross 308 strain in two developmental stages, after 3rd and 6th week of age, which were maintained in the same housing and feeding conditions. The obtained results show for the overexpression of genes related to orexigenic molecules, such as neuropeptide Y (NPY), aldehyde dehydrogenase 1 family, member A1 (ALDH1A1), galanin (GAL), and pro-melanin concentrating hormone (PMCH) in low GR cockerels.

Conclusion

The results reveal strong associations between satiety centre and the growth process. The present study delivers new insights into hypothalamic regulation in broiler chickens and narrows the area for the searching of genetic markers for GR.

Graphical abstract
Identification and distribution of gene clusters required for synthesis of sphingolipid metabolism inhibitors in diverse species of the filamentous fungus Fusarium
Authors: Kim Hye-Seon , Lohmar Jessica M. , Busman Mark , Brown Daren W. , Naumann Todd A. , Divon Hege H. , Lysøe Erik , Uhlig Silvio , Proctor Robert H.
Published: July 2020

Background

Sphingolipids are structural components and signaling molecules in eukaryotic membranes, and many organisms produce compounds that inhibit sphingolipid metabolism. Some of the inhibitors are structurally similar to the sphingolipid biosynthetic intermediate sphinganine and are referred to as sphinganine-analog metabolites (SAMs). The mycotoxins fumonisins, which are frequent contaminants in maize, are one family of SAMs. Due to food and feed safety concerns, fumonisin biosynthesis has been investigated extensively, including characterization of the fumonisin biosynthetic gene cluster in the agriculturally important fungiAspergillusandFusarium. Production of several other SAMs has also been reported in fungi, but there is almost no information on their biosynthesis. There is also little information on how widely SAM production occurs in fungi or on the extent of structural variation of fungal SAMs.

Results

Using fumonisin biosynthesis as a model, we predicted that SAM biosynthetic gene clusters in fungi should include a polyketide synthase (PKS), an aminotransferase and a dehydrogenase gene. Surveys of genome sequences identified five putative clusters with this three-gene combination in 92 of 186Fusariumspecies examined. Collectively, the putative SAM clusters were distributed widely but discontinuously among the species. We propose that the SAM5 cluster confers production of a previously reportedFusariumSAM, 2-amino-14,16-dimethyloctadecan-3-ol (AOD), based on the occurrence of AOD production only in species with the cluster and on deletion analysis of the SAM5 cluster PKS gene. We also identified SAM clusters in 24 species of other fungal genera, and propose that one of the clusters confers production of sphingofungin, a previously reportedAspergillusSAM.

Conclusion

Our results provide a genomics approach to identify novel SAM biosynthetic gene clusters in fungi, which should in turn contribute to identification of novel SAMs with applications in medicine and other fields. Information about novel SAMs could also provide insights into the role of SAMs in the ecology of fungi. Such insights have potential to contribute to strategies to reduce fumonisin contamination in crops and to control crop diseases caused by SAM-producing fungi.
Breeding history and candidate genes responsible for black skin of Xichuan black-bone chicken
Authors: Li Donghua , Sun Guirong , Zhang Meng , Cao Yanfang , Zhang Chenxi , Fu Yawei , Li Fang , Li Guoxi , Jiang Ruirui , Han Ruili , Li Zhuanjian , Wang Yanbin , Tian Yadong , Liu Xiaojun , Li Wenting , Kang Xiangtao
Published: July 2020

Background

Domesticated chickens have a wide variety of phenotypes, in contrast with their wild progenitors. Unlike other chicken breeds, Xichuan black-bone chickens have blue-shelled eggs, and black meat, beaks, skin, bones, and legs. The breeding history and the economically important traits of this breed have not yet been explored at the genomic level. We therefore used whole genome resequencing to analyze the breeding history of the Xichuan black-bone chickens and to identify genes responsible for its unique phenotype.

Results

Principal component and population structure analysis showed that Xichuan black-bone chicken is in a distinct clade apart from eight other breeds. Linkage disequilibrium analysis showed that the selection intensity of Xichuan black-bone chickens is higher than for other chicken breeds. The estimated time of divergence between the Xichuan black-bone chickens and other breeds is 2.89 ka years ago.Fstanalysis identified a selective sweep that contains genes related to melanogenesis. This region is probably associated with the black skin of the Xichuan black-bone chickens and may be the product of long-term artificial selection. A combined analysis of genomic and transcriptomic data suggests that the candidate gene related to the black-bone trait,EDN3, might interact with the upstream ncRNALOC101747896to generate black skin color during melanogenesis.

Conclusions

These findings help explain the unique genetic and phenotypic characteristics of Xichuan black-bone chickens, and provide basic research data for studying melanin deposition in animals.
Adverse clinical events caused by pacemaker battery depletion: two case reports
Authors: Liu Junpeng , Wen Li , Yao Simin , Zheng Peipei , Zhao Shuang , Yang Jiefu
Published: July 2020

Background

The clinical symptoms and adverse events caused by pacemaker battery depletion are not uncommon, but it is easy to miss or misdiagnose them clinically. To raise the level of awareness towards this clinical situation, we report two cases.

Case presentation

We described two cases of pacemaker battery depletion. Case 1 was an 83-year-old male manifesting chest pain and dyspnea. Automatic reprogramming after pacemaker battery depletion resulted in pacemaker syndrome. While case 2 was an 80-year-old female with complete atrioventricular heart block and torsade de pointes, due to complete depletion of pacemaker battery. In addition, we introduce a method that can easily identify the depletion of the pacemaker battery, which has clinical promotion value of a certain degree.

Conclusions

Those cases emphasize that serious morbidity can arise from pacemaker battery depletion, even in the early stages. Therefore, early detection and diagnosis is especially important.
Cultural adoption, and validation of the Persian version of the coronary artery disease education questionnaire (CADE-Q): a second-order confirmatory factor analysis
Authors: Marofi Zahra , Bandari Razieh , Heravi-Karimooi Majideh , Rejeh Nahid , Montazeri Ali
Published: July 2020

Background

Evaluating knowledge in patients with coronary artery disease requires a specific measure. The aim of the present study was to translate and evaluate the CADE-Q in patients with coronary artery disease in Iran.

Methods

Forward-backward procedure was applied to translate the questionnaire from English into Persian. Then a cross-sectional study was conducted to evaluate psychometric properties of the questionnaire. A sample of patients with coronary artery disease attending to cardiac departments of teaching hospitals affiliated to medical universities in Tehran, Iran completed the 19-item CADE-Q from April to December 2017. Structural validity of CADE-Q was assessed using both exploratory and confirmatory factor analyses. Reliability was examined using Cronbach’s alpha coefficient. Stability was evaluated by estimation intraclass correlation coefficient.

Results

In all 500 patients participated in the study. The mean age of patients was 53.63. (SD = 14.36) years, and 57% were male. The results obtained from the exploratory factor analysis showed a four factor solution (lifestyle habits and exercise, risk factors, diagnosis and treatment, signals & symptoms and medicine) that jointly explained 48.9% of the total variance observed. However, the second-order confirmatory factor analysis supported the three-factor solution while convergent and divergent validity were not confirmed. Finally, the Cronbach’s alpha coefficient of 0.84 ranging from 0.50 to 0.82 was obtained for the scale and its subscales. In addition, the ICC value of 0.88 showed satisfactory stability for the questionnaire.

Conclusion

The Coronary Artery Disease Education Questionnaire was found to be a multidimensional instrument. The results confirmed the factor structure of the questionnaire with a second-order analysis. Since the convergent and divergent validity of the scale were not confirmed, further assessment is essential to establish fitness of the questionnaire in Iran.
COVID-19 prevalence estimation by random sampling in population - optimal sample pooling under varying assumptions about true prevalence
Authors: Brynildsrud Ola
Published: July 2020

Background

The number of confirmed COVID-19 cases divided by population size is used as a coarse measurement for the burden of disease in a population. However, this fraction depends heavily on the sampling intensity and the various test criteria used in different jurisdictions, and many sources indicate that a large fraction of cases tend to go undetected.

Methods

Estimates of the true prevalence of COVID-19 in a population can be made by random sampling and pooling of RT-PCR tests. Here I use simulations to explore how experiment sample size and degrees of sample pooling impact precision of prevalence estimates and potential for minimizing the total number of tests required to get individual-level diagnostic results.

Results

Sample pooling can greatly reduce the total number of tests required for prevalence estimation. In low-prevalence populations, it is theoretically possible to pool hundreds of samples with only marginal loss of precision. Even when the true prevalence is as high as 10% it can be appropriate to pool up to 15 samples. Sample pooling can be particularly beneficial when the test has imperfect specificity by providing more accurate estimates of the prevalence than an equal number of individual-level tests.

Conclusion

Sample pooling should be considered in COVID-19 prevalence estimation efforts.
Colon perforation due to cytomegalovirus infection in a patient with idiopathic hypereosinophilic syndrome: a case report
Authors: Luo Bin , Deng Chengxin , Hou Tieying , Xu Fangping , Liao Qianchao , Li Yong , Wang Junjiang
Published: July 2020

Background

Hypereosinophilic syndrome (HES) is a very rare disease and usually treated with corticosteroids. Gastrointestinal (GI) cytomegalovirus (CMV) infection is also rare but frequent in patients with immunocompromised status. These two related diseases present with similar manifestations, and may result in a life-threatening complication: perforation. However, the treatment strategies differ greatly. Here, we report a case of colon perforation due to cytomegalovirus infection in a patient with idiopathic HES.

Case presentation

A 41-year-old man with a history of HES was transferred to our hospital due to an acute onset of abdominal pain. During the treatment course of HES, this patient received CMV-DNA test with a result of < 2000 copies/ml. Computed tomography (CT) suggested colon perforation. An emergency surgery was performed immediately. Pathological diagnosis revealed CMV infection and infiltration of eosinophils. This patient received both anti-CMV therapy and immunosuppression therapy. Subsequently, the patient recovered and was discharged 25 days after the operation.

Conclusion

During the course of HES treatment, CMV infection should be reconsidered if digestive symptoms relapse.
Bile pigment in small-bowel water content may reflect bowel habits: a retrospective analysis of a capsule endoscopy imaging series
Authors: Aoyama Taiki , Fukumoto Akira , Shigita Kenjiro , Asayama Naoki , Mukai Shinichi , Nagata Shinji
Published: July 2020

Background

Pigmented bile salts darken the small-bowel lumen and are present with bile acid, which is involved in the development of bowel habits. The small-bowel water content (SBWC) in the ileum could represent the colonic environment, but no studies have focused on this feature. However, measurement of crude SBWC can be challenging because of the technical difficulty of the endoscopic approach without preparation. Our aim was to evaluate optically active bile pigments in the SBWC of patients with abnormal bowel habits using capsule endoscopy (CE) to investigate the impact of bile acid on bowel habits.

Methods

The study population included 37 constipated patients, 20 patients with diarrhea, and 77 patients with normal bowel habits who underwent CE between January 2015 and May 2018. Patients with secondary abnormal bowel habits were excluded. In addition to conventional imaging, we used flexible spectral imaging color enhancement (FICE) setting 1 imaging, in which the effects of bile pigments on color are suppressed. Intergroup color differences of SBWC in the ileum (ΔE) were evaluated from conventional and FICE setting 1 images. Color values were assessed using the CIE L*a*b* color space. Differences in SBWC lightness (black to white, range 0–100) were also evaluated.

Results

The ΔE values from the comparison of conventional images between patients with constipation and with normal bowel habits and between patients with diarrhea and with normal bowel habits were 12.4 and 11.2, respectively. These values decreased to 4.4 and 3.3, respectively, when FICE setting 1 images were evaluated. Patients with constipation and diarrhea had significantly brighter (34.4 versus 27.6,P < .0001) and darker (19.6 versus 27.6,P < .0001) SBWC lightness, respectively, than patients with normal bowel habits. The FICE setting 1 images did not reveal significant differences in SBWC lightness between those with constipation and with normal bowel habits (44.1 versus 43.5,P = .83) or between those with diarrhea and with normal bowel habits (39.1 versus 43.5,P = .20).

Conclusions

Differences in SBWC color and darkness in the ileum appear to be attributable to bile pigments. Therefore, bile pigments in SBWC may reflect bowel habits.
Unusual presentation of fatal disseminated varicella zoster virus infection in a patient with lupus nephritis: a case report
Authors: Vassia Veronica , Croce Alessandro , Ravanini Paolo , Leutner Monica , Saglietti Chiara , Fangazio Stefano , Quaglia Marco , Smirne Carlo
Published: July 2020

Background

The risk of life-threatening complications, such as visceral disseminated varicella zoster virus (VZV) infection, is greater in immunosuppressed individuals, such as systemic lupus erythematosus (SLE) patients.

Case presentation

Here, a case is reported of a Caucasian woman diagnosed with lupus nephritis and anti-phospholipid syndrome, who was subjected to mycophenolate mofetil and high-dose steroid remission-induction therapy. Two months later she developed abdominal pain followed by a fatal rapid multi-organ failure. As no typical skin rashes were evident, death was initially attributed to catastrophic anti-phospholipid syndrome. However, autopsy and virological examinations on archival material revealed a disseminated VZV infection.

Conclusions

Overall, this case highlights the importance of having a high clinical suspicion of fatal VZV infections in heavily immunosuppressed SLE patients even when typical signs and symptoms are lacking.
Magnitude of screening for gestational diabetes mellitus in an urban setting in Tanzania; a cross-sectional analytic study
Authors: Mukuve Akampa , Noorani Mariam , Sendagire Ibrahim , Mgonja Miriam
Published: July 2020

Background

Medical screening detects risk factors for disease or presence of disease in otherwise well persons in order to intervene early and reduce morbidity and mortality. During antenatal care (ANC) it is important to detect conditions that complicate pregnancy, like gestational diabetes mellitus (GDM). Despite international and local guidelines recommending screening for GDM during ANC, there is evidence to suggest that the practice was not being carried out adequately. A major challenge may be lack of consensus on uniform GDM screening and diagnostic guidelines internationally and locally.

The primary objective was to determine the magnitude of screening for GDM among women receiving ANC at the Aga Khan Hospital, Dar es Salaam and Muhimbili National Hospital, Dar es Salaam. Secondary objectives were: to determine the methods used by health practitioners to screen for GDM, to determine the magnitude of undiagnosed gestational diabetes mellitus among women attending ANC and factors associated with screening for GDM among these women.

Methods

A cross-sectional analytical study was done. Data collection was done using pre-tested questionnaires and reviewing antenatal care records. The proportion of women attending ANC who were screened for GDM was determined. The 75 g Oral Glucose Tolerance Test (OGTT) was offered to women who had not been screened after education and consent.

Results

Only 107 out of 358 (29.9%) had been offered some form of GDM screening. Tests used for GDM screening were random blood sugar (56.8%), fasting blood sugar (32.8%), HbA1C (6%) and 75 g OGTT (3.4%). The uptake of the OGTT was 27%. Of these women the prevalence of GDM was 27.9%. Factors associated with screening for GDM were history of big baby, history of pregnancy induced hypertension and participant awareness of GDM (allp: < 0.05).

Conclusions

Screening for GDM among women attending ANC was lower than the World Health Organization target. Efforts should be directed towards promoting GDM screening, increasing awareness about GDM and developing more effective screening methods.
Neuropathy, claw toes, intrinsic muscle volume, and plantar aponeurosis thickness in diabetic feet
Authors: Kimura Tadashi , Thorhauer Eric D. , Kindig Matthew W. , Shofer Jane B. , Sangeorzan Bruce J. , Ledoux William R.
Published: July 2020

Background

The objective of this study was to explore the relationships between claw toe deformity, peripheral neuropathy, intrinsic muscle volume, and plantar aponeurosis thickness using computed tomography (CT) images of diabetic feet in a cross-sectional analysis.

Methods

Forty randomly-selected subjects with type 2 diabetes were selected for each of the following four groups (n = 10 per group): 1) peripheral neuropathy with claw toes, 2) peripheral neuropathy without claw toes, 3) non-neuropathic with claw toes, and 4) non-neuropathic without claw toes. The intrinsic muscles of the foot were segmented from processed CT images. Plantar aponeurosis thickness was measured in the reformatted sagittal plane at 20% of the distance from the most inferior point of the calcaneus to the most inferior point of the second metatarsal. Five measurement sites in the medial-lateral direction were utilized to fully characterize the plantar aponeurosis thickness. A linear mixed-effects analysis on the effects of peripheral neuropathy and claw toe deformity on plantar aponeurosis thickness and intrinsic muscle volume was performed.

Results

Subjects with concurrent neuropathy and claw toes had thicker mean plantar aponeurosis (p < 0.006) and may have had less mean intrinsic muscle volume (p = 0.083) than the other 3 groups. The effects of neuropathy and claw toes on aponeurosis thickness were synergistic rather than additive. A similar pattern may exist for intrinsic muscle volume, but results were not as conclusive. A negative correlation was observed between plantar aponeurosis thickness and intrinsic muscle volume (R2 = 0.323, p < 0.001).

Conclusions

Subjects with concurrent neuropathy and claw toe deformity were associated with the smallest intrinsic foot muscle volumes and the thickest plantar aponeuroses. Intrinsic muscle atrophy and plantar aponeurosis thickening may be related to the development of claw toes in the presence of neuropathy.
Marital status, an independent predictor for survival of gastric neuroendocrine neoplasm patients: a SEER database analysis
Authors: Zhou Yu-Jie , Lu Xiao-Fan , Zheng Kenneth I. , Wang Qi-Wen , Chen Jin-Nan , Zhang Qing-Wei , Yan Fang-Rong , Li Xiao-Bo
Published: July 2020

Background

Marital status proves to be an independent prognostic factor in a variety of cancers. However, its prognostic impact on gastric neuroendocrine neoplasms (G-NEN) has not been investigated.

Methods

We identified 3947 G-NEN patients from the Surveillance, Epidemiology, and End Results (SEER) database. Meanwhile, propensity scores for marital status were used to match 506 unmarried patients with 506 married patients. We used Kaplan–Meier method and multivariate Cox regression to analyse the association between marital status and the overall survival (OS) and G-NEN cause-specific survival (CSS) before matching and after matching.

Results

Married patients enjoyed better OS and CSS, compared with divorced/separated, single, and widowed patients. Multivariate Cox regression analysis indicated that unmarried status was associated with higher mortality hazards for both OS and CSS among G-NEN patients. Additionally, widowed individuals had the highest risks of overall (adjusted hazard ratio (HR): 1.56, 95% confidence interval (CI): 1.35–1.81, P < 0.001) and cancer-specific mortality (adjusted HR: 1.33, 95% CI: 1.05–1.68, P = 0.02) compared to other unmarried groups in both males and females. Furthermore, unmarried status remained an independent prognostic and risk factor for both OS (HR 1.51, 95% CI 1.19–1.90, P = 0.001) and CSS (HR 1.50, 95% CI 1.10–2.05, P = 0.01) in 1:1 propensity score-matched analysis.

Conclusion

Marital status was an independent prognostic factor for G-NEN. Meanwhile, widowed patients with G-NEN had the highest risk of death compared with single, married, and divorced/separated patients.
Perinatal mood and anxiety disorders, serious mental illness, and delivery-related health outcomes, United States, 2006–2015
Authors: McKee Kimberly , Admon Lindsay K. , Winkelman Tyler N. A. , Muzik Maria , Hall Stephanie , Dalton Vanessa K. , Zivin Kara
Published: July 2020

Background

National estimates of perinatal mood and anxiety disorders (PMAD) and serious mental illness (SMI) among delivering women over time, as well as associated outcomes and costs, are lacking. The prevalence of perinatal mood and anxiety disorders and serious mental illness from 2006 to 2015 were estimated as well as associated risk of adverse obstetric outcomes, including severe maternal morbidity and mortality (SMMM), and delivery costs.

Methods

The study was a serial, cross-sectional analysis of National Inpatient Sample data. The prevalence of PMAD and SMI was estimated among delivering women as well as obstetric outcomes, healthcare utilization, and delivery costs using adjusted weighted logistic with predictive margins and generalized linear regression models, respectively.

Results

The study included an estimated 39,025,974 delivery hospitalizations from 2006 to 2015 in the U.S. PMAD increased from 18.4 (95% CI 16.4–20.0) to 40.4 (95% CI 39.3–41.6) per 1000 deliveries. SMI also increased among delivering women over time, from 4.2 (95% CI 3.9–4.6) to 8.1 (95% CI 7.9–8.4) per 1000 deliveries. Medicaid covered 72% (95% CI 71.2–72.9) of deliveries complicated by SMI compared to 44% (95% CI 43.1–45.0) and 43.5% (95% CI 42.5–44.5) among PMAD and all other deliveries, respectively. Women with PMAD and SMI experienced higher incidence of SMMM, and increased hospital transfers, lengths of stay, and delivery-related costs compared to other deliveries (P < .001 for all).

Conclusion

Over the past decade, the prevalence of both PMAD and SMI among delivering women increased substantially across the United States, and affected women had more adverse obstetric outcomes and delivery-related costs compared to other deliveries.
Acceptability of quality indicators for the management of endometrial, cervical and ovarian cancer: results of an online survey
Authors: Luyckx Annemie , Wyckmans Leen , Bonte Anne-Sophie , Trinh Xuan Bich , van Dam Peter A.
Published: July 2020

Background

Measuring quality indicators (QI’s) is a tool to improve the quality of care. The aim of this study was to evaluate the acceptability of 36 QI’s, defined after a literature search for the management of endometrial, cervical and ovarian cancer. Relevant specialists in the field of interest were surveyed.

Methods

To quantify the opinions of these specialists, an online survey was sent out via mailing to members of gynaecological or oncological societies. The relevance of each QI was questioned on a scale from one to five (1 = irrelevant, 2 = less relevant, 3 = no opinion/neutral, 4 = relevant, 5 = very relevant). If a QI received a score of 4 or 5 in 65% or more of the answers, we state that the respondents consider this QI to be sufficiently relevant to use in daily practice.

Results

The survey was visited 238 times and resulted in 53 complete responses (29 Belgian, 24 other European countries). The majority of the specialists were gynaecologists (45%). Five of the 36 QI’s (13,9%) did not reach the cut-off of 65%: referral to a tertiary center, preoperative staging of endometrial cancer by MRI, preoperative staging of cervical cancer by positron-emission tomography, incorporation of intracavitary brachytherapy in the treatment of cervical cancer, reporting ASA and WHO score for each patient. After removing the 5 QI’s that were not considered as relevant by the specialists and 3 additional 3 QI’s that we were considered to be superfluous, we obtained an optimized QI list.

Conclusion

As QI’s gain importance in gynecological oncology, their use can only be of value if they are universally interpreted in the same manner. We propose an optimized list of 28 QI’s for the management of endometrial, cervical and ovarian cancer which responders of our survey found relevant. Further validation is needed to finalize and define a set of QI’s that can be used in future studies, audits and benchmarking.
Development and validation of a tool to assess the risk of QT drug-drug interactions in clinical practice
Authors: Berger Florine A. , van der Sijs Heleen , Becker Matthijs L. , van Gelder Teun , van den Bemt Patricia M. L. A.
Published: July 2020

Background

The exact risk of developing QTc-prolongation when using a combination of QTc-prolonging drugs is still unknown, making it difficult to interpret these QT drug-drug interactions (QT-DDIs). A tool to identify high-risk patients is needed to support healthcare providers in handling automatically generated alerts in clinical practice. The main aim of this study was to develop and validate a tool to assess the risk of QT-DDIs in clinical practice.

Methods

A model was developed based on risk factors associated with QTc-prolongation determined in a prospective study on QT-DDIs in a university medical center inthe Netherlands. The main outcome measure was QTc-prolongation defined as a QTc interval > 450 ms for males and > 470 ms for females. Risk points were assigned to risk factors based on their odds ratios. Additional risk factors were added based on a literature review. The ability of the model to predict QTc-prolongation was validated in an independent dataset obtained from a general teaching hospital against QTc-prolongation as measured by an ECG as the gold standard. Sensitivities, specificities, false omission rates, accuracy and Youden’s index were calculated.

Results

The model included age, gender, cardiac comorbidities, hypertension, diabetes mellitus, renal function, potassium levels, loop diuretics, and QTc-prolonging drugs as risk factors. Application of the model to the independent dataset resulted in an area under the ROC-curve of 0.54 (95% CI 0.51–0.56) when QTc-prolongation was defined as > 450/470 ms, and 0.59 (0.54–0.63) when QTc-prolongation was defined as > 500 ms. A cut-off value of 6 led to a sensitivity of 76.6 and 83.9% and a specificity of 28.5 and 27.5% respectively.

Conclusions

A clinical decision support tool with fair performance characteristics was developed. Optimization of this tool may aid in assessing the risk associated with QT-DDIs.

Trial registration

No trial registration, MEC-2015-368.
Improving shared decision-making in vascular surgery by implementing decision support tools: study protocol for the stepped-wedge cluster-randomised OVIDIUS trial
Authors: de Mik S. M. L. , Stubenrouch F. E. , Legemate D. A. , Balm R. , Ubbink D. T.
Published: July 2020

Background

Shared decision-making improves the quality of patient care. Unfortunately, shared decision-making is not yet common practice among vascular surgeons. Thus, decision support tools were developed to assist vascular surgeons and their patients in using shared decision-making. This trial aims to evaluate the effectiveness and implementation of decision support tools to improve shared decision-making during vascular surgical consultations in which a treatment decision is to be made.

Methods

The study design is a multicentre stepped-wedge cluster-randomised trial. Eligible patients are adult patients, visiting the outpatient clinic of a participating medical centre for whom several treatment options are feasible and who face a primary treatment decision for their abdominal aortic aneurysm, carotid artery disease, intermittent claudication, or varicose veins. Patients and vascular surgeons in the intervention group receive decision support tools that may help them adopt shared decision-making when making the final treatment decision. These decision support tools are decision aids, consultation cards, decision cards, and a practical training. Decision aids are informative websites that help patients become more aware of the pros and cons of the treatment options and their preferences regarding the treatment choice. Consultation cards with text or decision cards with images are used by vascular surgeons during consultation to determine which aspect of a treatment is most important to their patient. In the training vascular surgeons can practice shared decision-making with a patient actor, guided by a medical psychologist. This trial aims to include 502 vascular surgical patients to achieve a clinically relevant improvement in shared decision-making of 10 out of 100 points, using the 5-item OPTION instrument to score the audio-recordings of consultations.

Discussion

In the OVIDIUS trial the available decision support tools for vascular surgical patients are implemented in clinical practice. We will evaluate whether these tools actually improve shared decision-making in the consultation room. The stepped-wedge cluster-randomised study design will ensure that at the end of the study all participating centres have implemented at least some of the decision support tools and thereby a certain level of shared decision-making.

Trial registration

Netherlands Trial Registry, NTR6487. Registered 7 June 2017. URL: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6487
Normalizing inconvenience to promote childhood vaccination: a qualitative implementation evaluation of a novel Michigan program
Authors: Lillvis Denise F. , Willison Charley , Noyes Katia
Published: July 2020

Background

In 2015, Michigan implemented a rule requiring parents to attend an education session at a local health department (LHD) prior to waiving mandatory child vaccinations. This study utilizes Normalization Process Theory (NPT) to assess program implementation, identifying potential threats to fidelity and sustainability.

Methods

We conducted 32 semi-structured interviews with individuals involved in these education programs across 16 LHDs. Participating LHDs were selected from a stratified, representative sample. One interviewer conducted all interviews using a semi-structured interview guide; two authors coded and analyzed the interview transcripts according to the NPT framework (i.e, sense-making, engagement, collective action, and reflexive monitoring).

Results

There was a lack of consensus about who the stakeholders of this new rule and its resulting program were (sense-making). Perhaps as a result, most LHDs did not solicit advice from key stakeholder groups (i.e., schools, health care providers, community stakeholders) in their planning (engagement). While most interviewees identified providing education and information as the goal, some identified the more challenging goal of persuading vaccine hesitant parents to immunize their children. There was also some variation in perception of who held health educators accountable for meeting the goals of the waiver education program (collective action). Formal program evaluation by LHDs was rare, although some held informal staff debriefings. Additionally, sessions that went particularly well or poorly were top-of-mind (reflexive monitoring).

Conclusions

The immunization waiver education program may be at risk of not becoming fully embedded into routine LHD practice, potentially compromising its long-term effectiveness and sustainability. Managers at the local and state level should maintain oversight to ensure that the program is delivered with fidelity. As the program relies on sustaining inconvenience to encourage parents to immunize their children, any shortcuts taken will undermine its success.
Surgery scheduling heuristic considering OR downstream and upstream facilities and resources
Authors: Calegari Rafael , Fogliatto Flavio S. , Lucini Filipe R. , Anzanello Michel J. , Schaan Beatriz D.
Published: July 2020

Background

Surgical theater (ST) operations planning is a key subject in the healthcare management literature, particularly the scheduling of procedures in operating rooms (ORs). The OR scheduling problem is usually approached using mathematical modeling and made available to ST managers through dedicated software. Regardless of the large body of knowledge on the subject, OR scheduling models rarely consider the integration of OR downstream and upstream facilities and resources or validate their propositions in real life, rather using simulated scenarios. We propose a heuristic to sequence surgeries that considers both upstream and downstream resources required to perform them, such as surgical kits, post anesthesia care unit (PACU) beds, and surgical teams (surgeons, nurses and anesthetists).

Methods

Using hybrid flow shop (HFS) techniques and the break-in-moment (BIM) concept, the goal is to find a sequence that maximizes the number of procedures assigned to the ORs while minimizing the variance of intervals between surgeries’ completions, smoothing the demand for downstream resources such as PACU beds and OR sanitizing teams. There are five steps to the proposed heuristic: listing of priorities, local scheduling, global scheduling, feasibility check and identification of best scheduling.

Results

Our propositions were validated in a high complexity tertiary University hospital in two ways: first, applying the heuristic to historical data from five typical ST days and comparing the performance of our proposed sequences to the ones actually implemented; second, pilot testing the heuristic during ten days in the ORs, allowing a full rotation of surgical specialties. Results displayed an average increase of 37.2% in OR occupancy, allowing an average increase of 4.5 in the number of surgeries performed daily, and reducing the variance of intervals between surgeries’ completions by 55.5%. A more uniform distribution of patients’ arrivals at the PACU was also observed.

Conclusions

Our proposed heuristic is particularly useful to plan the operation of STs in which resources are constrained, a situation that is common in hospital from developing countries. Our propositions were validated through a pilot implementation in a large hospital, contributing to the scarce literature on actual OR scheduling implementation.
The gut bacterial diversity of sheep associated with different breeds in Qinghai province
Authors: Chang Jianjun , Yao Xiaoting , Zuo Chenxiang , Qi Yuxu , Chen Dekun , Ma Wentao
Published: July 2020

Background

Gut microbiota play important roles in their co-evolution with mammals. However, little is understood about gut bacterial community of Tibetan sheep compared with other sheep breeds. In this study, we investigated the gut bacterial community in 4 different sheep breeds living in the Qinghai-Tibetan Plateau (QTP) of China using high-throughput sequencing (HTS) technique.

Results

The results suggested that bacterial community abundance and breeds diversity of Tibetan sheep (TS) were significantly lower than that of the other three breeds of sheep [Dorset sheep (DrS), Dorper sheep (DrS) and Small Tail Han sheep (STHS)] (p < 0.05). Principal coordinates analysis (PCoA) and nonmetric multidimensional scaling (NMDS) analysis indicated that microbiome composition of TS was significantly different from that of other three sheep breeds (p < 0.01). Firmicutes was the most predominant microbial phylum in the gut, followed by Bacteroidetes. The gut bacterial community of TS showed higher proportions of phylum Spirochaetes, Proteobacteria and Verrucomicrobia, compared to the other three sheep breeds, but the Deferribacteres was absent in TS. At the genus level, Treponema, Succinivibrio, 5-7 N15 and Prevotella showed significantly higher abundance in TS than in the other three sheep breeds (p < 0.05).

Conclusions

In this study, we first employed HTS to understand the gut microbiomes among different sheep breeds in QTP of China.
LncRNA ANRIL/miR-7-5p/TCF4 axis contributes to the progression of T cell acute lymphoblastic leukemia
Authors: Li Gang , Gao Lan , Zhao Jing , Liu Dejun , Li Hui , Hu Min
Published: July 2020

Background

Antisense non-coding RNA in the INK4 locus (ANRIL) is of great importance in cell biological behaviors, and ANRIL functions in many kinds of cancers including leukemia. However, the mechanism of ANRIL in the progression of T-cell acute lymphoblastic leukemia (T-ALL) has not been clarified clearly.

Methods

qRT-PCR was performed to detect ANRIL expression in T-ALL samples. T-ALL cell lines (MOLT4, CCRF-CEM and KOPT-K1) were used as the cell models. The function of ANRIL on T-ALL cells was investigated by CCK-8 assays, Transwell assays, and apoptosis experiments in vitro. qRT-PCR, Western blot, luciferase reporter assay and RIP assay were used to confirm the interactions between ANRIL and miR-7-5p, miR-7-5p and its target gene transcription factor 4 (TCF4).

Results

ANRIL was significantly up-regulated in T-ALL samples. Its knockdown markedly inhibited viability, migration and invasion of T-ALL cells, but its overexpression exerted the opposite effects. TCF4 was proved to be a target gene of miR-7-5p. ANRIL down-regulated miR-7-5p via sponging it and in turn up-regulated TCF4.

Conclusions

LncRNA ANRIL can modulate malignant phenotypes of T-ALL cells, possibly by regulating miR-7-5p/TCF4 axis, and it serves as a potential therapeutic target for T-ALL.
Pathophysiology and neurologic sequelae of cerebral malaria
Authors: Schiess Nicoline , Villabona-Rueda Andres , Cottier Karissa E. , Huether Katherine , Chipeta James , Stins Monique F.
Published: July 2020

Cerebral malaria (CM), results from Plasmodium falciparum infection, and has a high mortality rate. CM survivors can retain life-long post CM sequelae, including seizures and neurocognitive deficits profoundly affecting their quality of life. As the Plasmodium parasite does not enter the brain, but resides inside erythrocytes and are confined to the lumen of the brain’s vasculature, the neuropathogenesis leading to these neurologic sequelae is unclear and under-investigated. Interestingly, postmortem CM pathology differs in brain regions, such as the appearance of haemorragic punctae in white versus gray matter. Various host and parasite factors contribute to the risk of CM, including exposure at a young age, parasite- and host-related genetics, parasite sequestration and the extent of host inflammatory responses. Thus far, several proposed adjunctive treatments have not been successful in the treatment of CM but are highly needed. The region-specific CM neuro-pathogenesis leading to neurologic sequelae is intriguing, but not sufficiently addressed in research. More attention to this may lead to the development of effective adjunctive treatments to address CM neurologic sequelae.
Predictors of health workers’ knowledge about artesunate-based severe malaria treatment recommendations in government and faith-based hospitals in Kenya
Authors: Machini Beatrice , Zurovac Dejan , Amboko Beatrice , Malla Lucas , Snow Robert W. , Kipruto Hillary , Achia Thomas N. O.
Published: July 2020

Background

Health workers’ knowledge deficiencies about artesunate-based severe malaria treatment recommendations have been reported. However, predictors of the treatment knowledge have not been examined. In this paper, predictors of artesunate-based treatment knowledge among inpatient health workers in two hospital sectors in Kenya are reported.

Methods

Secondary analysis of 367 and 330 inpatient health workers randomly selected and interviewed at 47 government hospitals in 2016 and 43 faith-based hospitals in 2017 respectively, was undertaken. Multilevel ordinal and binary logistic regressions examining the effects of 11 factors on five knowledge outcomes in government and faith-based hospital sectors were performed.

Results

Among respective government and faith-based health workers, about a third of health workers had high knowledge of artesunate treatment policies (30.8% vs 32.9%), a third knew all dosing intervals (33.5% vs 33.3%), about half knew preparation solutions (49.9% vs 55.8%), half to two-thirds knew artesunate dose for both weight categories (50.8% vs 66.7%) and over three-quarters knew the preferred route of administration (78.7% vs 82.4%). Eight predictors were significantly associated with at least one of the examined knowledge outcomes. In the government sector, display of artesunate administration posters, paediatric ward allocation and repeated surveys were significantly associated with more than one of the knowledge outcomes. In the faith-based hospitals, availability of artesunate at hospitals and health worker pre-service training were associated with multiple outcomes. Exposure to in-service malaria case-management training and access to malaria guidelines were only associated with higher knowledge about artesunate treatment policy.

Conclusion

Programmatic interventions ensuring display of artesunate administration posters in the wards, targeting of health workers managing adult patients in the medical wards, and repeated knowledge assessments are likely to be beneficial for improving the knowledge of government health workers about artesunate-based severe malaria treatment recommendations. The availability of artesunate and focus on improvements of nurses’ knowledge should be prioritized at the faith-based hospitals.