bluuebunny/crossref_metadata_2025 huggingface dataset:
Correction to: Multimodal analgesia with ropivacaine wound infiltration and intravenous flurbiprofen axetil provides enhanced analgesic effects after radical thyroidectomy: a randomized controlled trial
Authors: Li Xiaoxi , Yu Ling , Yang Jiaonan , Tan Hongyu
Published: November 2019

Following publication of the original article [1], the authors reported that there has been a mistake regarding the unit of duration of surgery, consciousness recovery time, and extubation time in Table 1; the correct unit is minute.
Prediction mapping of human leptospirosis using ANN, GWR, SVM and GLM approaches
Authors: Mohammadinia Ali , Saeidian Bahram , Pradhan Biswajeet , Ghaemi Zeinab
Published: November 2019

Background

Recent reports of the National Ministry of Health and Treatment of Iran (NMHT) show that Gilan has a higher annual incidence rate of leptospirosis than other provinces across the country. Despite several efforts of the government and NMHT to eradicate leptospirosis, it remains a public health problem in this province. Modelling and Prediction of this disease may play an important role in reduction of the prevalence.

Methods

This study aims to model and predict the spatial distribution of leptospirosis utilizing Geographically Weighted Regression (GWR), Generalized Linear Model (GLM), Support Vector Machine (SVM) and Artificial Neural Network (ANN) as capable approaches. Five environmental parameters of precipitation, temperature, humidity, elevation and vegetation are used for modelling and predicting of the disease. Data of 2009 and 2010 are used for training, and 2011 for testing and evaluating the models.

Results

Results indicate that utilized approaches in this study can model and predict leptospirosis with high significance level. To evaluate the efficiency of the approaches, MSE (GWR = 0.050, SVM = 0.137, GLM = 0.118 and ANN = 0.137), MAE (0.012, 0.063, 0.052 and 0.063), MRE (0.011, 0.018, 0.017 and 0.018) and R2(0.85, 0.80, 0.78 and 0.75) are used.

Conclusion

Results indicate the practical usefulness of approaches for spatial modelling and predicting leptospirosis. The efficiency of models is as follow: GWR > SVM > GLM > ANN. In addition, temperature and humidity are investigated as the most influential parameters. Moreover, the suitable habitat of leptospirosis is mostly within the central rural districts of the province.
Capsular warning syndrome: clinical analysis and treatment
Authors: He Lanying , Xu Ronghua , Wang Jian , Zhang Lili , Zhang Lijuan , Zhou Fangfang , Dong Weiwei
Published: November 2019

Background

Capsular warning syndrome (CWS) is a rare clinical syndrome, which is defined as a recurrent transient lacunar syndrome. The mechanism and clinical management of CWS remain unclear. The aim of the study was to discuss the clinical characteristics of CWS and evaluate the different outcome between rt-PA and no rt-PA therapy.

Methods

The present multicenter retrospective study involved three medical centers, and the clinical data were collected from patients with CWS between January 2013 and December 2018. The clinical characteristics of CWS were analyzed. Patients were divided into two groups: rt-PA and no rt-PA groups. The therapeutic effects and prognosis of these two groups were analyzed. A good prognosis was defined as 3-month modified Rankin Scale (mRS) ≤ 2.

Results

Our study included 72 patients, 27 patients were assigned to rt-PA group, 45 in no rt-PA group. Hypertension and dyslipidemia were the most common risk factors. The mean number of episodes before irreversible neurological impairment or the symptoms completely disappeared was five times (range: 3–11 times). A total of 58 (80.55%) patients had acute infarction lesions on the diffusion weighted imaging (DWI). The most common infarct location was the internal capsule (41,70.69%), followed by the thalamus and pons. The difference in therapeutic effects between the rt-PA, single and double antiplatelet groups was not statistically significant (P > 0.05). A good prognosis was observed in 61 (84.72%) patients after 3 months, in which 23 (23/27, 85.19%) patients were from the rt-PA group and 38 (38/45,84.44%) patients were from the no rt-PA group (P > 0.05). After 3 months of follow-up, two patients had recurrent ischemic stroke.

Conclusion

The most effective treatment of CWS remains unclear. Intravenous thrombolysis is safe for CWS patients. Regardless of the high frequency of infarction in CWS patients, more than 80% patients had a favorable functional prognosis.
Impact of the intervention program “JolinchenKids – fit and healthy in daycare” on energy balance related-behaviors: results of a cluster controlled trial
Authors: Steenbock Berit , Buck Christoph , Zeeb Hajo , Rach Stefan , Pischke Claudia R.
Published: November 2019

Background

The purpose of this study was to evaluate the multi-component health promotion program, JolinchenKids – fit and healthy in daycare, designed to promote physical activity (PA), healthy eating, and mental wellbeing among 3- to 6-year-old preschoolers.

Methods

For this cluster controlled trial, 62 daycare facilities (DFs) from thirteen different federal states in Germany were recruited (31 intervention, 31 control DFs). Outcome measures were children’s habitual PA, fruits and vegetable consumption, consumption of unsweetened beverages and snacks with parents as raters. Study nurses assessed children’s body composition and motor skills. Data was collected at baseline and 12 months later. To track adherence to the implementation of intervention modules at individual DF groups, an implementation calendar was used from baseline to follow-up. Linear mixed models were used to investigate effects for survey, group and their interaction at the individual level while accounting for clustering.

Results

Samples of 831 (baseline) and 641 (follow-up) children aged 4.3 ± 0.8 and 5.2 ± 0.8 years were analysed. More than half of the intervention DFs chose the nutrition or PA module for the first year of implementation while an implementation level of > 50% was only achieved in less than a third. A significant intervention effect (survey × group interaction) was found for the standing long jump favouring children at intervention DFs (β = 3.08; 95% Confidence interval [CI]: (0.09; 6.07)). No significant intervention effects were found for time spent on PA, total screen time, dietary habits, and body composition, i.e. body-mass-index and percentage of body fat.

Conclusions

Participation in JolinchenKids – fit and healthy in daycare led to improvements in some indicators for motor skills. However, other health outcomes and behaviours were not affected by program participation over the course of 1 year.

Trial registration

German Clinical Trials Register DRKS00011065 (Date of registration 16-09-2016).
Non-inferior comparative study comparing one or two day antimicrobial prophylaxis after clean orthopaedic surgery (NOCOTA study): a study protocol for a cluster pseudo-randomized controlled trial comparing duration of antibiotic prophylaxis
Authors: Nagata Kosei , Yamada Koji , Shinozaki Tomohiro , Miyazaki Tsuyoshi , Tokimura Fumiaki , Oka Hiroyuki , Tajiri Yasuhito , Tanaka Sakae , Okazaki Hiroshi
Published: November 2019

Background

Antimicrobial prophylaxis (AMP) is one of the most important measures for preventing surgical site infections (SSIs); however, controversies remain regarding its adequate duration. Although the World Health Organization and the Center for Disease Control and Prevention do not recommend additional AMP after closure, the American Society of Health-System Pharmacists and the Musculoskeletal Infection Society permit the use of postoperative AMP, but recommend discontinuation within 24 h. Similarly, the Japanese Society of Chemotherapy and the Japan Society for Surgical Infection also permit AMP within 24–48 h after various orthopaedic procedures. In these guidelines, recommendations regarding AMP duration were weak due to a relative lack of evidence, and currently, there is no high-quality evidence comparing AMP use within 24 h versus 24–48 h regarding orthopaedic procedures. Urinary tract infection (UTI) and respiratory tract infection (RTI) are also important health care-associated infections (HAIs) faced after surgery. Although AMP duration may affect these HAIs, its effects have not been well evaluated.

Methods

We have organized a multicenter, prospective, cluster pseudo-randomized controlled trial to examine the non-inferiority of shorter AMP duration (within 24 h) against longer duration (24–48 h) in preventing postoperative HAIs. Participating facilities will be divided into two groups. In Group 24, AMP will be discontinued within 24 h after surgery. In Group 48, AMP will be discontinued within 24–48 h after surgery. The group allocation will be switched every 2 months until the targeted recruitment (500 participants per group) is met.

The primary outcome will be the cumulative incidence of all HAIs (SSI, UTI, RTI, and other infectious diseases), which require antibiotic therapies within 30 days after surgery. In addition to mortality and cardiovascular events, prolonged hospitalization (> 30 days) and the rate of antibiotic resistance rate of SSI pathogens will also be evaluated. Outcomes will be evaluated within 30–180 days after surgery in person by the surgeon, by mail, or by telephone survey. Data will be analyzed by a statistician not engaged in data collection.

Discussion

This study may provide valuable information for developing future recommendations for adequate AMP duration after clean orthopaedic surgery.

Trial registration

UMIN000030929, registered January 22, 2018.
Feet deformities and their close association with postural stability deficits in children aged 10–15 years
Authors: Szczepanowska-Wolowiec Beata , Sztandera Paulina , Kotela Ireneusz , Zak Marek
Published: November 2019

Background

Children and young people make up an age group most vulnerable to falls. Various stability disorders may become instrumental in sustaining more frequent falls and resultant fractures. Correct morphological structure impacts overall efficiency of the foot, as well as offers significant diagnostic potential. Even minor foot disorders may affect the entire bio kinematic chain, also impacting the foot’s motility. Structural alterations within a foot may also impair balance in the standing position, and contribute to more frequent injuries. The study aimed to assess the relationship between feet deformities and postural stability deficits in schoolchildren prone to sustain accidental falls.

Methods

The study involved 200 children (101 girls and 99 boys) aged 10–15 years,

randomly selected from primary schools. A 2D podoscan was used to assess the plantar part of the foot, while stabilometric examination was aided by the FreeMed dynamometric platform.

Results

Correlation between respective variables was reflected by Spearman’s rank coefficient. The subjects’ age negatively correlated with the COP range of movement along the Y axis, and the COP surface area, while their BMI negatively correlated with the COP trajectory’s length. Step regression analysis indicated that the width of the left foot, the left foot Wejsflog index, the left foot Clark’s angle, the hallux valgus angle were the essential predictors of stabilometric variables in girls. In boys, though, predictive value was associated with Clarke’s angle of the left and right foot, Wejsflog index of the right foot, and the width of both the left and right foot.

Conclusions

There is a statistically significant correlation between morphological variables of the foot and postural stability. When assessing the key variables of the foot and their interrelationship with postural stability, the Clarke’s angle, Wejsflog index, hallux valgus angle, and foot width, should be granted due prominence in the girls. As regards the boys, the following variables were established as predictive in assessing postural stability: Clarke’s angle, Wejsflog index, and foot width.
Integrative molecular analysis of metastatic hepatocellular carcinoma
Authors: Wang Dongfang , Zhu Yanjing , Tang Jing , Lian Qiuyu , Luo Guijuan , Wen Wen , Zhang Michael Q. , Wang Hongyang , Chen Lei , Gu Jin
Published: November 2019

Background

Hepatocellular carcinoma (HCC) is the major type of primary liver cancer. Intrahepatic metastasis, such as portal vein tumor thrombosis (PVTT), strongly indicates poor prognosis of HCC. But now, there are limited understandings of the molecular features and mechanisms of those metastatic HCCs.

Methods

To characterize the molecular alterations of the metastatic HCCs, we implemented an integrative analysis of the copy number variations (CNVs), DNA methylations and transcriptomes of matched adjacent normal, primary tumor and PVTT samples from 19 HCC patients.

Results

CNV analysis identified a frequently amplified focal region chr11q13.3 and a novel deletion peak chr19q13.41 containing three miRNAs. The integrative analysis with RNA-seq data suggests that CNVs and differential promoter methylations regulate distinct oncogenic processes. Then, we used individualized differential analysis to identify the differentially expressed genes between matched primary tumor and PVTT of each patient. Results show that 5 out of 19 studied patients acquire evidential progressive alterations of gene expressions (more than 1000 differentially expressed genes were identified in each patient). While, another subset of eight patients have nearly identical gene expressions between the corresponding matched primary tumor and PVTT. Twenty genes were found to be recurrently and progressively differentially expressed in multiple patients. These genes are mainly associated with focal adhesion, xenobiotics metabolism by cytochrome P450 and amino acid metabolism. For several differentially expressed genes in metabolic pathways, their expressions are significantly associated with overall survivals and vascular invasions of HCC patients. The following transwell assay experiments validate that they can regulate invasive phenotypes of HCC cells.

Conclusions

The metastatic HCCs with PVTTs have significant molecular alterations comparing with adjacent normal tissues. The recurrent alteration patterns are similar to several previously published general HCC cohorts, but usually with higher severity. By an individualized differential analysis strategy, the progressively differentially expressed genes between the primary tumor and PVTT were identified for each patient. A few patients aquire evidential progressive alterations of gene expressions. And, experiments show that several recurrently differentially expressed genes can strongly regulate HCC cell invasions.
Lysine pathway metabolites and the risk of type 2 diabetes and cardiovascular disease in the PREDIMED study: results from two case-cohort studies
Authors: Razquin Cristina , Ruiz-Canela Miguel , Clish Clary B. , Li Jun , Toledo Estefania , Dennis Courtney , Liang Liming , Salas-Huetos Albert , Pierce Kerry A. , Guasch-Ferré Marta , Corella Dolores , Ros Emilio , Estruch Ramon , Gómez-Gracia Enrique , Fitó Montse , Lapetra Jose , Romaguera Dora , Alonso-Gómez Angel , Serra-Majem Lluis , Salas-Salvadó Jordi , Hu Frank B. , Martínez-González Miguel A.
Published: November 2019

Background

The pandemic of cardiovascular disease (CVD) and type 2 diabetes (T2D) requires the identification of new predictor biomarkers. Biomarkers potentially modifiable with lifestyle changes deserve a special interest. Our aims were to analyze: (a) The associations of lysine, 2-aminoadipic acid (2-AAA) or pipecolic acid with the risk of T2D or CVD in the PREDIMED trial; (b) the effect of the dietary intervention on 1-year changes in these metabolites, and (c) whether the Mediterranean diet (MedDiet) interventions can modify the effects of these metabolites on CVD or T2D risk.

Methods

Two unstratified case-cohort studies nested within the PREDIMED trial were used. For CVD analyses, we selected 696 non-cases and 221 incident CVD cases; for T2D, we included 610 non-cases and 243 type 2 diabetes incident cases. Metabolites were quantified using liquid chromatography–tandem mass spectrometry, at baseline and after 1-year of intervention.

Results

In weighted Cox regression models, we found that baseline lysine (HR+1 SD increase = 1.26; 95% CI 1.06–1.51) and 2-AAA (HR+1 SD increase = 1.28; 95% CI 1.05–1.55) were both associated with a higher risk of T2D, but not with CVD. A significant interaction (p = 0.032) between baseline lysine and T2D on the risk of CVD was observed: subjects with prevalent T2D and high levels of lysine exhibited the highest risk of CVD. The intervention with MedDiet did not have a significant effect on 1-year changes of the metabolites.

Conclusions

Our results provide an independent prospective replication of the association of 2-AAA with future risk of T2D. We show an association of lysine with subsequent CVD risk, which is apparently diabetes-dependent. No evidence of effects of MedDiet intervention on lysine, 2-AAA or pipecolic acid changes was found.

Trial registration ISRCTN35739639; registration date: 05/10/2005; recruitment start date 01/10/2003
Salinomycin effectively eliminates cancer stem-like cells and obviates hepatic metastasis in uveal melanoma
Authors: Zhou Jingfeng , Liu Shenglan , Wang Yun , Dai Wei , Zou Hailin , Wang Shubo , Zhang Jing , Pan Jingxuan
Published: November 2019

Background

Uveal melanoma (UM) is the most common primary intraocular tumor. Hepatic metastasis is the major and direct death-related reason in UM patients. Given that cancer stem-like cells (CSCs) are roots of metastasis, targeting CSCs may be a promising strategy to overcome hepatic metastasis in UM. Salinomycin, which has been identified as a selective inhibitor of CSCs in multiple types of cancer, may be an attractive agent against CSCs thereby restrain hepatic metastasis in UM. The objective of the study is to explore the antitumor activity of salinomycin against UM and clarify its underlying mechanism.

Methods

UM cells were treated with salinomycin, and its effects on cell proliferation, apoptosis, migration, invasion, CSCs population, and the related signal transduction pathways were determined. The in vivo antitumor activity of salinomycin was evaluated in the NOD/SCID UM xenograft model and intrasplenic transplantation liver metastasis mouse model.

Results

We found that salinomycin remarkably obviated growth and survival in UM cell lines and in a UM xenograft mouse model. Meanwhile, salinomycin significantly eliminated CSCs and efficiently hampered hepatic metastasis in UM liver metastasis mouse model. Mechanistically, Twist1 was fundamental for the salinomycin-enabled CSCs elimination and migration/invasion blockage in UM cells.

Conclusions

Our findings suggest that targeting UM CSCs by salinomycin is a promising therapeutic strategy to hamper hepatic metastasis in UM. These results provide the first pre-clinical evidence for further testing of salinomycin for its antitumor efficacy in UM patients with hepatic metastasis.
A systematic review of instruments for the analysis of national-level physical activity and sedentary behaviour policies
Authors: Klepac Pogrmilovic Bojana , O’Sullivan Grant , Milton Karen , Biddle Stuart J. H. , Pedisic Zeljko
Published: November 2019

Background

This systematic review aimed to identify and critically assess available instruments for the analysis of national-level physical activity (PA) and sedentary behaviour (SB) policies and provide recommendations for their future use.

Methods

We conducted a systematic search of academic and grey literature through six bibliographic databases, Google and the websites of three international organisations for PA promotion to identify instruments that are used or that may be used for national-level PA/SB policy analysis. In order to describe and categorise the identified instruments, we used the Comprehensive Analysis of Policy on Physical Activity framework. This framework specifies the elements of a comprehensive analysis of PA/SB policies through the following categories: purpose, level, policy sector, type of policy, stages of policy cycle and scope of analysis.

Results

Out of 22,071 screened items, 26 publications describing 16 instruments met the selection criteria. All the instruments can be used for analysing PA policy, whilst only two include questions about SB policy. None of the instruments allow for the analysis of all the relevant components of national PA/SB policy. Some important elements of PA policy analysis, such as the tourism and research sectors, the agenda-setting and endorsement/legitimisation stages, and the effects of policy, are addressed by only a few instruments. Moreover, none of the instruments address unwritten formal statements, informal policies, and the termination and succession stages of the policy cycle.

Conclusion

Designing new instruments or adapting existing ones is needed to allow for a more thorough analysis of national PA and SB policies. Given that policy analysis covering all important components of PA/SB policy may be extremely time-consuming, a way forward might be to develop a set of complementary instruments, with each tool collecting detailed information about a specific component.
Chromatin accessibility and transcription dynamics during in vitro astrocyte differentiation of Huntington’s Disease Monkey pluripotent stem cells
Authors: Goodnight Alexandra V. , Kremsky Isaac , Khampang Sujittra , Jung Yoon Hee , Billingsley James M. , Bosinger Steven E. , Corces Victor G. , Chan Anthony W. S.
Published: November 2019

Background

Huntington’s Disease (HD) is a fatal neurodegenerative disorder caused by a CAG repeat expansion, resulting in a mutant huntingtin protein. While it is now clear that astrocytes are affected by HD and significantly contribute to neuronal dysfunction and pathogenesis, the alterations in the transcriptional and epigenetic profiles in HD astrocytes have yet to be characterized. Here, we examine global transcription and chromatin accessibility dynamics during in vitro astrocyte differentiation in a transgenic non-human primate model of HD.

Results

We found global changes in accessibility and transcription across different stages of HD pluripotent stem cell differentiation, with distinct trends first observed in neural progenitor cells (NPCs), once cells have committed to a neural lineage. Transcription of p53 signaling and cell cycle pathway genes was highly impacted during differentiation, with depletion in HD NPCs and upregulation in HD astrocytes. E2F target genes also displayed this inverse expression pattern, and strong associations between E2F target gene expression and accessibility at nearby putative enhancers were observed.

Conclusions

The results suggest that chromatin accessibility and transcription are altered throughout in vitro HD astrocyte differentiation and provide evidence that E2F dysregulation contributes to aberrant cell-cycle re-entry and apoptosis throughout the progression from NPCs to astrocytes.
Optimality and duality results for E-differentiable multiobjective fractional programming problems under E-convexity
Authors: Antczak Tadeusz , Abdulaleem Najeeb
Published: November 2019

A new class of (not necessarily differentiable) multiobjective fractional programming problems with E-differentiable functions is considered. The so-called parametric E-Karush–Kuhn–Tucker necessary optimality conditions and, under E-convexity hypotheses, sufficient E-optimality conditions are established for such nonsmooth vector optimization problems. Further, various duality models are formulated for the considered E-differentiable multiobjective fractional programming problems and several E-duality results are derived also under appropriate E-convexity hypotheses.
DNA barcoding confirms the first record of a Desmodema polystictum (Ogilby, 1898) egg and all-time high adult catches in the Indian Ocean
Authors: Rathnasuriya M. I. G. , Mateos-Rivera A. , Bandara A. G. G. C. , Skern-Mauritzen R. , Jayasinghe R. P. P. K. , Krakstad J. O. , Dalpadado P.
Published: November 2019

The eggs of Polka-dot ribbonfish Desmodema polystictum have been recorded for the first time in the Indian Ocean. Although the only previous information on eggs from this species consists of line drawings from 1973 (Pacific Ocean), the identification was possible by combining morphological and molecular analyses. As far as we are aware, only few confirmed records of adult individuals have been previously reported from the Indian Ocean. We found eggs in the proximity of numerous adults (57 and 42 individuals at two stations) indicating that the Central Indian Ocean is potentially an important spawning ground of D. polystictum.
New records of marine decapods and stomatopods in Área de Conservación Guanacaste (ACG): four years of marine biodiversity inventorying
Authors: Vargas-Castillo Rita , Cortés Jorge
Published: November 2019

The marine area of Área de Conservación Guanacaste (ACG) contains a 43,000 ha formal marine protected area, a 732 ha special management zone in Bahía Santa Elena, and 150 km of wild protected coastline. In an effort to broaden the biodiversity knowledge of all marine taxa present in the area, an inventory was started in 2015 (BioMar-ACG Project). This initiative is being funded by the Guanacaste Dry Forest Conservation Fund (GDFCF) in collaboration with government staff at ACG, and is carried out by Centro de Investigación en Ciencias del Mar y Limnología (CIMAR, Center for Research in Marine Science and Limnology) and Museo de Zoología (Zoology Museum), both from Universidad de Costa Rica (UCR). After four years of the project, 2650 specimens of marine decapod crustaceans and stomatopods have been collected, belonging to 209 species, out of which 99 are new records for ACG, four may be new species and nine (Cyrtoplax panamensis, Glyptoxanthus labyrinthicus, Pachyches marcortezensis, Petrolisthes donadio, Pylopagurus holmesi, Synalpheus pinkfloydi, Typton granulosus, Zenopontonia soror, Neogonodactylus pumilus) are new records for Costa Rica. With this contribution the total number of decapods (257 spp.) and stomatopods (14 spp.) for ACG is 271 species, more than half the species reported for Costa Rica, and more than a quarter of all crustaceans reported for the eastern tropical Pacific. The high concentration of species in ACG may be attributed to the diversity of habitats, the seasonal upwelling and to the recent sampling efforts. In only four years, the BioMar-ACG has increased the number of species in these groups of crustaceans by 37% over the past 85 years of previous studies in the ACG.
A case report of rare location of ganglioglioma
Authors: Sharma Vikas , Bhaskar S. , Hire Sumit Ramdas , Ahuja Arvind
Published: November 2019

Background

Gangliogliomas are rare tumors of the central nervous system. They can occur anywhere in the central nervous system but are most commonly located in the temporal lobe and are mainly found in children. Anaplastic ganglioglioma can result from either de novo or transformation of a pre-existing lesion.

Case presentation

We report a case of de novo anaplastic ganglioglioma in the parieto occipital region, which is a rare location. A 34-year-old lady presented with features of raised intracranial pressure (ICP) with right side hemiparesis. Contrast-enhanced magnetic resonance imaging (CEMRI) of the brain showed well-defined intense heterogenously enhancing solid cystic mass lesion 5.3 × 5.2 cm in the left parieto occipital region with mass effect and midline shift. Intraoperatively, a cystic mass lesion with reddish brown nodule was seen in the left occipital lobe. Complete tumor excision was done. Microscopic and IHC examination was suggestive of anaplastic ganglioglioma. The post-operative period was uneventful. The patient received 60-Gy radiotherapy with temozolamide as adjuvant therapy, and repeat imaging showed no tumor recurrence.

Conclusion

Anaplastic gangliogliomas are rare tumors with parieto occipital as rare location.
TarGo: network based target gene selection system for human disease related mouse models
Authors: Hyung Daejin , Mallon Ann-Marie , Kyung Dong Soo , Cho Soo Young , Seong Je Kyung
Published: November 2019

Genetically engineered mouse models are used in high-throughput phenotyping screens to understand genotype-phenotype associations and their relevance to human diseases. However, not all mutant mouse lines with detectable phenotypes are associated with human diseases. Here, we propose the “Target gene selection system for Genetically engineered mouse models” (TarGo). Using a combination of human disease descriptions, network topology, and genotype-phenotype correlations, novel genes that are potentially related to human diseases are suggested. We constructed a gene interaction network using protein-protein interactions, molecular pathways, and co-expression data. Several repositories for human disease signatures were used to obtain information on human disease-related genes. We calculated disease- or phenotype-specific gene ranks using network topology and disease signatures. In conclusion, TarGo provides many novel features for gene function prediction.
The importance of harmonising diagnostic criteria sets for pathological grief
Authors: Lenferink Lonneke I. M. , Boelen Paul A. , Smid Geert E. , Paap Muirne C. S.
Published: November 2019

Five diagnostic criteria sets for pathological grief are currently used in research. Studies evaluating their performance indicate that it is not justified to generalise findings regarding prevalence rates and predictive validity across studies using different diagnostic criteria of pathological grief. We provide recommendations to move the bereavement field forward.
Results of a Multicenter Phase II Study of Atezolizumab and Bevacizumab for Patients With Metastatic Renal Cell Carcinoma With Variant Histology and/or Sarcomatoid Features
Authors: McGregor Bradley A. , McKay Rana R. , Braun David A. , Werner Lillian , Gray Kathryn , Flaifel Abdallah , Signoretti Sabina , Hirsch Michelle S. , Steinharter John A. , Bakouny Ziad , Flippot Ronan , Wei Xiao X. , Choudhury Atish , Kilbridge Kerry , Freeman Gordon J. , Van Allen Eliezer M. , Harshman Lauren C. , McDermott David F. , Vaishampayan Ulka , Choueiri Toni K.
Published: November 2019

PURPOSE

In this multicenter phase II trial, we evaluated atezolizumab combined with bevacizumab in patients with advanced renal cell carcinoma (RCC) with variant histology or any RCC histology with ≥ 20% sarcomatoid differentiation.

PATIENTS AND METHODS

Eligible patients may have received previous systemic therapy, excluding prior bevacizumab or checkpoint inhibitors. Patients underwent a baseline biopsy and received atezolizumab 1,200 mg and bevacizumab 15 mg/kg intravenously every 3 weeks. The primary end point was overall response rate (ORR) by RECIST version 1.1. Additional end points were progression-free survival (PFS), toxicity, biomarkers of response as determined by programmed death-ligand 1 (PD-L1) status, and on-therapy quality-of-life (QOL) metrics using the Functional Assessment of Cancer Therapy Kidney Symptom Index-19 and the Brief Fatigue Inventory.

RESULTS

Sixty patients received at least 1 dose of either study agent; the majority (65%) were treatment naïve. The ORR for the overall population was 33% and 50% in patients with clear cell RCC with sarcomatoid differentiation and 26% in patients with variant histology RCC. Median PFS was 8.3 months (95% CI, 5.7 to 10.9 months). PD-L1 status was available for 36 patients; 15 (42%) had ≥ 1% expression on tumor cells. ORR in PD-L1–positive patients was 60% (n = 9) v 19% (n = 4) in PD-L1–negative patients. Eight patients (13%) developed treatment-related grade 3 toxicities. There were no treatment-related grade 4-5 toxicities. QOL was maintained throughout therapy.

CONCLUSION

In this study, atezolizumab and bevacizumab demonstrated safety and resulted in objective responses in patients with variant histology RCC or RCC with ≥ 20% sarcomatoid differentiation. This regimen warrants additional exploration in patients with rare RCC, particularly those with PD-L1–positive tumors.
Obstructive Sleep Apnea in Acromegaly and the Effect of Treatment: A Systematic Review and Meta-Analysis
Authors: Parolin Matteo , Dassie Francesca , Alessio Luigi , Wennberg Alexandra , Rossato Marco , Vettor Roberto , Maffei Pietro , Pagano Claudio
Published: November 2019

Background

Obstructive sleep apnea (OSA) is a common disorder characterized by upper airway collapse requiring nocturnal ventilatory assistance. Multiple studies have investigated the relationship between acromegaly and OSA, reporting discordant results.

Aim

To conduct a meta-analysis on the risk for OSA in acromegaly, and in particular to assess the role of disease activity and the effect of treatments.

Methods and Study Selection

A search through literature databases retrieved 21 articles for a total of 24 studies (n = 734). Selected outcomes were OSA prevalence and apnea-hypopnea index (AHI) in studies comparing acromegalic patients with active (ACT) vs inactive (INACT) disease and pretreatment and posttreatment measures. Factors used for moderator and meta-regression analysis included the percentage of patients with severe OSA, patient sex, age, body mass index, levels of insulin-like growth factor 1, disease duration and follow-up, and therapy.

Results

OSA prevalence was similar in patients with acromegaly who had ACT and INACT disease (ES = −0.16; 95% CI, −0.47 to 0.15; number of studies [k] = 10; P = 0.32). In addition, AHI was similar in ACT and INACT acromegaly patients (ES = −0.03; 95% CI, −0.49 to 0.43; k = 6; P = 0.89). When AHI was compared before and after treatment in patients with acromegaly (median follow-up of 6 months), a significant improvement was observed after treatment (ES = −0.36; 95% CI, −0.49 to −0.23; k = 10; P < 0.0001). In moderator analysis, the percentage of patients with severe OSA in the populations significantly influenced the difference in OSA prevalence (P = 0.038) and AHI (P = 0.04) in ACT vs INACT patients.

Conclusion

Prevalence of OSA and AHI is similar in ACT and INACT patients in cross-sectional studies. However, when AHI was measured longitudinally before and after treatment, a significant improvement was observed after treatment.
Weight Loss Improves β-Cell Function in People With Severe Obesity and Impaired Fasting Glucose: A Window of Opportunity
Authors: Rothberg Amy E , Herman William H , Wu Chunyi , IglayReger Heidi B , Horowitz Jeffrey F , Burant Charles F , Galecki Andrzej T , Halter Jeffrey B
Published: November 2019

Background

In people with obesity, β-cell function may adapt to insulin resistance. We describe β-cell function in people with severe obesity and normal fasting glucose (NFG), impaired fasting glucose (IFG), and type 2 diabetes (T2DM), as assessed before, 3 to 6 months after, and 2 years after medical weight loss to describe its effects on insulin sensitivity, insulin secretion, and β-cell function.

Methods

Fifty-eight participants with body mass index (BMI) ≥ 35 kg/m2 (14 with NFG, 24 with IFG, and 20 with T2DM) and 13 normal weight participants with NFG underwent mixed meal tolerance tests to estimate insulin sensitivity (S[I]), insulin secretion (Φ), and β-cell function assessed as model-based Φ adjusted for S(I). All 58 obese participants were restudied at 3 to 6 months and 27 were restudied at 2 years.

Results

At 3 to 6 months, after a 20-kg weight loss and a decrease in BMI of 6 kg/m2, S(I) improved in all obese participants, Φ decreased in obese participants with NFG and IFG and tended to decrease in obese participants with T2DM, and β-cell function improved in obese participants with NFG and tended to improve in obese participants with IFG. At 2 years, β-cell function deteriorated in participants with NFG and T2DM but remained significantly better in participants with IFG compared to baseline.

Conclusions

Short-term weight loss improves β-cell function in participants with NFG and IFG, but β-cell function tends to deteriorate over 2 years. In participants with IFG, weight loss improves longer-term β-cell function relative to baseline and likely relative to no intervention, suggesting that obese people with IFG are a subpopulation whose β-cell function is most likely to benefit from weight loss.
Review: Diabetes, Obesity, and Cancer—Pathophysiology and Clinical Implications
Authors: Lega Iliana C , Lipscombe Lorraine L
Published: November 2019

Obesity and diabetes have both been associated with an increased risk of cancer. In the face of increasing obesity and diabetes rates worldwide, this is a worrying trend for cancer rates. Factors such as hyperinsulinemia, chronic inflammation, antihyperglycemic medications, and shared risk factors have all been identified as potential mechanisms underlying the relationship. The most common obesity- and diabetes-related cancers are endometrial, colorectal, and postmenopausal breast cancers. In this review, we summarize the existing evidence that describes the complex relationship between obesity, diabetes, and cancer, focusing on epidemiological and pathophysiological evidence, and also reviewing the role of antihyperglycemic agents, novel research approaches such as Mendelian Randomization, and the methodological limitations of existing research. In addition, we also describe the bidirectional relationship between diabetes and cancer with a review of the evidence summarizing the risk of diabetes following cancer treatment. We conclude this review by providing clinical implications that are relevant for caring for patients with obesity, diabetes, and cancer and provide recommendations for improving both clinical care and research for patients with these conditions.
A Prospective, Randomized, Double-Blinded Study of the Effect of Intravenous Ondansetron on the Effective Dose in 50% of Subjects of Prophylactic Phenylephrine Infusions for Preventing Spinal Anesthesia–Induced Hypotension During Cesarean Delivery
Authors: Xiao Fei , Wei Changna , Chang Xiangyang , Zhang Yinfa , Xue Lili , Shen Huaxiang , Ngan Kee Warwick D. , Chen Xinzhong
Published: November 2019

BACKGROUND:

Ondansetron has been shown to reduce the incidence of hypotension and vasopressor requirement during spinal anesthesia for obstetric and nonobstetric surgery. However, the magnitude of this effect has not been fully quantified. In this parallel-group, randomized, double-blinded study, we determined the effective dose in 50% of subjects (ED50) of a prophylactic phenylephrine infusion for preventing hypotension in patients who received a single dose of intravenous ondansetron 4 mg or saline control before combined spinal–epidural anesthesia for elective cesarean delivery. ED50 values obtained were compared to estimate the effect of ondansetron versus placebo on vasopressor requirement.

METHODS:

Sixty parturients were randomly assigned to receive ondansetron (group O) or saline control (group C) 10 minutes before positioning for induction of spinal anesthesia. A prophylactic phenylephrine infusion was used to prevent hypotension. The first patient in each group received a phenylephrine infusion at the rate of 0.5 µg/kg/min. The infusion rate for each subsequent patient was varied with increments or decrements of 0.05 µg/kg/min based on the response of the previous patient, and the effective dose of the phenylephrine infusion for preventing hypotension in 50% of patients (ED50) was calculated for each group and compared using up-down sequential analysis. Probit regression was applied as a backup and sensitivity analysis was used to compare ED50 values for phenylephrine between groups by comparing calculated relative mean potency.

RESULTS:

The ED50 (mean [95% confidence interval (CI)]) of the rate of phenylephrine infusion was lower in group O (0.24 µg/kg/min [0.10–0.38 µg/kg/min]) compared with group C (0.32 µg/kg/min [0.14–0.47 µg/kg/min]) (P < .001). The total consumption of phenylephrine (mean ± standard deviation [SD]) until delivery was lower in group O (316.5 ± 25.9 µg) than in group C (387.7 ± 14.7 µg, P = .02). The estimate of relative median potency for phenylephrine for group O versus group C was 0.74 (95% CI, 0.37–0.95).

CONCLUSIONS:

Under the conditions of this study, intravenous ondansetron 4 mg reduced the ED50 of a prophylactic phenylephrine infusion by approximately 26% in patients undergoing cesarean delivery under combined spinal–epidural anesthesia.
Calculation of Confidence Intervals for Differences in Medians Between Groups and Comparison of Methods
Authors: Staffa Steven J. , Zurakowski David
Published: November 2019

Continuous data that are not normally distributed are typically presented in terms of median and interquartile range (IQR) for each group. High-quality anesthesia journals often require that confidence intervals are calculated and presented for all estimated associations of interest reported within a manuscript submission, and therefore, methods for calculating confidence intervals for differences in medians are vital. It is informative to present the difference in medians along with a confidence interval to provide insight about the magnitude of variability for the estimated difference. In a clinical research example using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Pediatric database, we demonstrate how to estimate confidence intervals for the difference in medians using 3 different statistical methods: the Hodges-Lehmann estimator, bootstrap resampling with replacement, and quantile regression modeling on the median (median regression). We discuss specific recommendations regarding the methods according to the objectives of the study as well as the distribution of the data as it pertains to the assumptions of the respective methods. Quantile regression allows for covariate adjustment, which may be an advantage in situations where differences in medians between groups may be due to confounding.
Analysis of rural egg production to improve the economy of the Andean communities in Ecuador
Authors: Bravo Avalos María Belén , Vaca Cárdenas Maritza , López Salazar José Luis , Herrera Chico María Fernanda , Villamarín Padilla Jenny Margoth
Published: November 2019

Background: An economically active population refers to people involved in any economic activity, such as agriculture, livestock, or industry. This activity can supply benefits to its owners and may generate the growth of small businesses. Our study presents a qualitative analysis of the egg production in Ecuadorian Andean communities (Tzimbuto, Bayushig "La Liberad," and La Victoria "Pusuca.")

Methods: Analysis was performed using a random sample of 81 hens and 29 eggs obtained from 65 producers, belonging to 50 farming families at the Utopia Community Fair. Zoometric characterization of the hens was carried out according to FAO protocols, and egg yolk quality, egg width and weight, and egg shell weight and thickness were calculated. The 65 producers were interviewed to answer questions pertaining to selling eggs, costs of production, and realized profit. The profit/cost indicator was calculated from the ratio of expenditure (egress) and total revenue of egg sales.

Results: 84% of surveyed participants indicated that they purchase eggs for their nutritional value, 12% because the animals are raised with organic food, and 4% showed preference for the eggs’ special flavor. The quality analysis of the eggs sold at the Fair demonstrated that the average weight of the eggs was 47.24 g; the length was 55.24 mm; and the width was 41.66 mm; weight and thickness of the shell were 4.90 g and 0.42 mm, respectively. The color of the yolk had a brightness of 57.62 L*, 5.53 a* for red/green tones and 47.15 b* for yellow/blue tones. The costs to produce the eggs for the Fair was US$0.21 with a profit/cost of US$0.04 per egg; the unit sale price is US$0.25.

Conclusions: 84% of surveyed participants indicated that they purchase eggs for their nutritional value, revealing the need to train the communities toward more efficient egg production.
The Human Right of Reproduction: Ovum Donation and Surrogacy
Authors: Rosenau Henning
Published: November 2019

The right to reproduction, including the use of modern methods of fertility medicine, is well founded on constitutional grounds and is protected by the Constitution Germany and of Estonia as well. This right is protected also at the level of European human rights, by Article 8 of the European Convention on Human Rights, which addresses the right to a private and family life. In light of Article 8(2) of that convention, restrictions to these are deemed legitimate only when they are based on scientifically valid evidence and to protect the wellbeing of the child. The author concludes that the current state of scientific knowledge gives insufficient reason to justify prohibition of ovum donation and surrogate motherhood. Said prohibition discriminates against people who rely on such methods (thereby infringing on Article 14 of the European Convention on Human Rights and Article 3(1) of the German Basic Law). Therefore, ovum donation and surrogacy should be allowed by law, as is proposed under sections 6 and 8 of the proposal for a modern law on reproductive medicine (AME-FMedG) issued by the Augsburg and Munich Working Group of medical ethics lawyers.
Is Full Preference for a Secured Claim in Insolvency Proceedings Justified?
Authors: Kasak Anto
Published: November 2019

Secured claims have priority over other claims in the event of debtor insolvency with respect to the distribution of the debtor’s encumbered assets. Numerous writings have discussed the necessity of security instruments in the context of growth and development of the economy. Credit is indeed necessary for the economy’s development, but, at the same time, credit is the cause of insolvency. This can be put another way: efficient credit develops the economy, while inefficient credit causes insolvency. The author argues on this basis that restriction of the secured creditor’s rights in insolvency proceedings means not less credit but more effective credit. A security-holder whose rights are limited is going to lend more responsibly and monitor the activity of the debtor more intensively and effectively, because the risk of loss would otherwise increase. Better monitoring should lead also to earlier intervention by the secured creditor in the actions of the debtor, which can be expected to increase the number of cases of rescue of debtors headed for insolvency. The author suggests the option of removing a small amount from the secured creditor and distributing it among the unsecured creditors to make the credit system more efficient and reduce injustice. Implementing this option would not harm the interests of the secured creditor as much as it helps to render the whole system more efficient.
Improvement of the Training System: Case Blizko.Ru
Authors: Fedorenko A.
Published: November 2019

Successful development of personnel, and with them the company is impossible without continuous improvement of skills and abilities, that is, without proper training of personnel. The income of the company, the opinion of customers and the prosperity of the company depend on the qualifi cation of the staff . The article presents an overview of the basic concepts and stages of the process of training and development of personnel. A study of the system of personnel training information portal BLIZKO.ru — analysis of documents, interviews with HR-Manager, an employee survey — helped to embed the system of training of personnel both in the administrative (development provisions for staff training, Supplement to the staff instructions of the personnel Manager) and meaningful (training) aspects. The social eff ect of the implemented measures is realized as an increase in the level of satisfaction with training, the level of competitiveness of the employee (professional mobility, the ability to acquire new knowledge, skills and practical skills), the compliance of professional training of the employee with the strategy of personnel management BLIZKO.ru.