bluuebunny/crossref_metadata_2025 huggingface dataset:
Drink (Socially) and Be Merry: Predicting Enjoyment and Self-Perceptions From Alcohol Consumption Among College Students
Authors: Hamilton Hannah R. , Armeli Stephen , Tennen Howard
Published: August 2020

Although many college students view drinking as a means of gaining a community and being social, research has not established whether alcohol consumption influences students’ enjoyment and perceptions of how others view them or how this may differ based on the social or solitary nature of that consumption. The current study used online daily diary methods to examine the association between alcohol consumption and enjoyment and self-perceptions at the within- and between-person levels of analysis. Results indicated that undergraduate students ( N = 877, 52% female) enjoyed their evenings more when they consumed more than their typical number of drinks with others but enjoyed evenings less when they consumed more than their typical number of drinks alone. In addition, consuming greater than their average number of drinks with others (but not alone) was related to feeling more social and attractive but less competent. These findings further highlight the distinct nature of social and solitary drinking and demonstrate positive outcomes of social alcohol consumption that may contribute to college alcohol consumption.
Outcomes of Meaningful Work in the Context of Indian Blue-collar Employees: The Moderating Role of Relational Identification and Organisation-based Self-esteem
Authors: Jena Lalatendu Kesari , Pattnaik Subhra
Published: August 2020

The study investigates the moderating effect of relational identification and organisation-based self-esteem (OBSE) on the relationship between meaningful work and prudence, as well as meaningful work and civic virtue behaviour, in the context of blue-collar employees working in the Indian aeronautical manufacturing sector (IAMS). Survey data collected from 312 blue-collar employees showed that meaningful work has a positive influence on prudence as well as civic virtue behavior only at high levels of relational identification and OBSE. These relationships were insignificant at the lower level of the moderators. The findings of the study hold significant research, practice, and societal implications, because meaningful work in the context of blue-collar employees of the aeronautical industry has not been studied before, though this industry has high growth potential.
Does Having a Rotator Cuff Repair Before Total Shoulder Arthroplasty Influence Outcomes?
Authors: Erickson Brandon J. , Ling Daphne , Wong Alexandra , Dines Joshua S. , Dines David M. , Gulotta Lawrence V.
Published: August 2020

Background:

The number of rotator cuff repairs (RCRs) is increasing each year. Total shoulder arthroplasty (TSA) is a successful treatment option for patients with glenohumeral osteoarthritis with a functioning rotator cuff.

Purpose/Hypothesis:

The purposes of this study were to report the outcomes of TSA in patients with ipsilateral RCR and determine whether patients with a history of ipsilateral RCR who subsequently underwent TSA had differences in outcomes compared with matched controls who underwent TSA with no history of RCR. We hypothesized that patients with prior RCR will have significant improvements in clinical outcome scores, with no difference in outcomes after TSA compared with those with no prior RCR.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

Patients eligible for inclusion were those with a history of prior RCR who underwent TSA at a single institution with a minimum 2-year follow-up between 2000 and 2015. Outcomes for this group, including American Shoulder and Elbow Surgeons (ASES) scores, were reported and then compared with a matched control group of patients who underwent TSA with no history of prior RCR. Controls were matched based on age, sex, and preoperative ASES score.

Results:

Overall, 14 patients (64% males; mean ± SD age, 65.1 ± 11.1 years) underwent prior ipsilateral RCR before TSA. ASES scores significantly improved from 42.9 to 78.5 at 2 years and to 86.6 at 5 years. When compared with 42 matched control patients (matched 1:3) who underwent TSA with no history of RCR, there was no significant difference in ASES scores at 2 years (78.5 vs 85.3; P = .19) and 5 years (86.6 vs 90.9; P = .72) between the prior RCR and no RCR groups.

Conclusion:

TSA in patients with a history of prior ipsilateral RCR led to significant improvements in clinical outcomes. No difference in clinical outcomes at 2 or 5 years after TSA was found between patients with and without a history of prior ipsilateral RCR.
Teacher Staffing Challenges in California: Examining the Uniqueness of Rural School Districts
Authors: Goldhaber Dan , Strunk Katharine O. , Brown Nate , Naito Natsumi , Wolff Malcolm
Published: August 2020

Using unique data from California on teacher job vacancies, we investigate staffing challenges across the urbanicity spectrum, focusing on the extent to which the characteristics of rural school systems explain the differences in staffing challenges as measured by vacancy rates and emergency credentialed teachers, relative to other urbanicities. We find that rural districts have significantly and substantially higher staffing challenges than districts from different urbanicity classifications (urban, suburban, and towns). Some of these differences are explained by district-level attributes, such as the proportion of students in poverty in the district. The geography of rural districts itself also explains the high levels of staffing challenge as rural districts are more likely to be located on a state border and far from teacher education programs, both of which are strongly associated with staffing challenge measures. Even after controlling for a rich set of observable covariates, there is evidence that rural districts are still somewhat more likely to face staffing challenges, suggesting that there are unobserved aspects of being rural associated with the desirability of employment that are not readily captured by quantitative data.
The local structures of human mobility in Chicago
Authors: Saxon James
Published: August 2020

A large literature establishes the role of mobility in the maintenance of neighborhood social structures. Jane Jacobs famously argued that social capital is maintained through “cross-use of space,” and James Coleman formalized its dependence on the “closure” of human interactions. Since many of these interactions entail human movement, neighborhoods with higher social capital should be distinguishable by more cohesive mobility networks. I observe the mobility of Chicago residents through a large dataset of smartphone users. I construct a neighborhood-level mobility network for the city and characterize neighborhoods according to their local graph structure. Neighborhoods that are well integrated with their surroundings have higher income and educational attainment. Consistent with social capital theory and routine activity theory in criminology, higher local network integration independently predicts lower levels of violent and property crime. The methodologies presented provide a meaningful, replicable, and inexpensive approach to the structural measurement of neighborhood networks and social structure.
Effect of Psychotropic Medications on Hammertoe Reconstruction Outcomes
Authors: Maidman Samuel D. , Nash Amalie E. , Fantry Amanda , Tenenbaum Shay , Daoud Yahya , Brodsky James , Bariteau Jason T.
Published: August 2020

Background:

Hammertoe deformities can seriously affect activity level and footwear. The use of prescription, mood-altering medications is very common, with some estimates as high as 25% of the population. Mood disorders, especially depression, negatively affect the results of medical and operative treatments. This study assessed the relationship of mood-altering medication use with the outcomes and complications of operative reconstruction of hammertoes.

Methods:

Data were prospectively collected from 116 patients who underwent hammertoe reconstruction, including demographic information, medical history, the use of mood-altering psychotropic medications (antidepressants, anxiolytics, hypnotics, and mood stabilizers), and postoperative complications. Preoperative patient-reported outcomes were measured using the visual analog scale (VAS) for pain and Short Form Health Survey (SF-36), which were repeated at 1-year follow-up.

Results:

A total of 36.2% of patients were taking psychotropic medications. Medication and nonmedication groups had similar pain VAS and SF-36 Physical Component Summary (PCS) scores before and after surgery. Compared with nonmedication patients, patients on psychotropic medications had significantly lower SF-36 Mental Component Summary (MCS) scores preoperatively ( P = .001) and postoperatively ( P = .006), but no significant difference in the change in MCS (ΔMCS) from preoperative to postoperative. Psychotropic medication use was associated with superficial wound infections ( P = .048), but not other complications.

Conclusions:

Patients taking psychotropic medications were equally likely to benefit from forefoot reconstruction as nonmedication patients. Preoperative and postoperative PCS and VAS were not significantly different between medication and nonmedication groups. Although the medication group had lower absolute MCS, they reported the same magnitude of improvement in MCS (ΔMCS) as the nonmedication group.

Level of Evidence:

Level II, prospective cohort study.
Autofluorescence indexes as biomarkers for antiangiogenic loading dose outcome in diabetic macular edema
Authors: Hernández Da Mota Sergio E. , Béjar Cornejo Francisco , Esquivel Velázquez Marcela , Lima Gómez Virgilio , González Saldívar Gerardo , Rodríguez Ayala Ernesto , Vélez-Montoya Raul
Published: August 2020

Purpose:

To evaluate the combination of fundus autofluorescence results with several clinical and structural variables into mathematical indexes to enhance their ability to predict visual and anatomical changes after the antivascular endothelial growth factor loading dose.

Methods:

Patients with diabetic macular edema were enrolled. Each patient had a comprehensive ophthalmological examination, contrast sensitivity, optical coherence tomography, and fundus autofluorescence assessment. All patients received three monthly doses of ziv-aflibercept and were followed each month for response assessment. Autofluorescence was classified according to its level into five grades. The grades were combined with other variables (best-corrected visual acuity, contrast sensitivity, central macular thickness, macular cube volume, and macular cube average thickness) into normalized indexes. Statistical assessment was done using a Spearman’s rank correlation coefficient, linear regression, and interobserver-agreement analysis.

Results:

There was a strong correlation between the fundus autofluorescence/baseline best-corrected visual acuity index and the fundus autofluorescence/contrast-sensitivity index at baseline with the best-corrected visual acuity after the third dose of ziv-aflibercept ( rs = −0.78, p = .000 and rs = −0.68, p = .0009 respectively). The fundus autofluorescence/baseline best-corrected visual acuity index and the fundus autofluorescence/contrast-sensitivity index, both at baseline had a mild correlation with the macular volume at 1 month of follow-up ( rs = 0.56, p = .008 and ( rs = 0.64, p = .002, respectively).

Conclusion:

This study suggests that it is possible to combine fundus autofluorescence results with functional and structural variables into normalized indexes that could potentially predict outcomes after antivascular endothelial growth factor loading dose in patients with diabetic macular edema.
Performance Evaluation of Agro-tourism Clusters using AHP–TOPSIS
Authors: Joshi Sudhanshu , Sharma Manu , Singh R. K.
Published: August 2020

The aim of this article is to recognize the key critical success factors (CSFs) that determine the performance of agritourism clusters using combined analytical hierarchy process (AHP)-the technique for order of preference by similarity to ideal solution (TOPSIS) method. The operational performance of agritourism clusters was determined using integrated approach, and 11 CSFs were initially identified through systematic literature review. Furthermore, experts validated and finalized nine CSFs that can determine the sustainable performance of agritourism network. Totally 15 experts (including practitioners and agritourism supply chain partners), were engaged in data collection process. The AHP application exhibits that destination attractiveness (D5) has the highest priority (0.156) among all the dimensions followed by local community contribution and sustainable livelihoods (D9). Furthermore, TOPSIS demonstrates that Pithoragarh (C7) has the ideal best value (0.7705) indicating that this cluster is performing the best among all the clusters followed by Almora (0.7209). The identification of CSFs to evaluate the performance of clusters in Uttarakhand, India can serve as guiding tool for the agritourism practitioners. The examination of pertinent issues with the focus on major support required, bottlenecks in adoption, key benefits of sustainable agritourism activities and most common sustainable practices are expected to provide new understanding about the sustainable agritourism business-based issues in India. The only limitation of this study is the geographic coverage and limited demography of the respondents. This study is one of the first efforts on assessing agritourism supply chain practices in India, with the special reference to Uttarakhand state.
Five decades of low intensity and low survival: adapting intensified regimens to cure pediatric Burkitt lymphoma in Africa
Authors: Ozuah Nmazuo W. , Lubega Joseph , Allen Carl E. , El-Mallawany Nader Kim
Published: August 2020

Long-term cure of childhood Burkitt lymphoma (BL) in sub-Saharan Africa after treatment with single-agent cyclophosphamide has been documented for more than half of a century. Contemporary cure rates for the highest-risk patients with BL in high-income countries exceed 90% using intensive multiagent chemotherapy. By contrast, the majority of African children with BL still die. Data spanning 5 decades in Africa have repeatedly shown that the children most likely to achieve cure with limited cyclophosphamide regimens are those with lower-stage disease isolated to the jaw. Attempts to intensify the cyclophosphamide monotherapy backbone with the addition of vincristine, low-dose methotrexate, prednisone, doxorubicin, and/or low-dose cytarabine have not yielded significant improvement. High-dose methotrexate is a critical component in the treatment of childhood BL worldwide. Although initial efforts in Africa to incorporate high-dose methotrexate resulted in high treatment-related mortality, more recent collaborative experiences from North and West Africa, as well as Central America, demonstrate that it can be administered safely and effectively, despite limitations in supportive care resources. Recognizing the unacceptable disparity in curative outcomes for BL between the United States/Europe and equatorial Africa, there is a critical need to safely adapt contemporary treatment regimens to optimize curative outcomes amid the resource limitations in regions where BL is endemic. Here, we critically review reports of BL treatment outcomes from low- and middle-income countries, in addition to data from high-income countries that predated modern intensified regimens, to identify potential strategies to improve the therapeutic approach for children suffering from BL in sub-Saharan Africa.
Determination of the phenotypic age in residents of Mexico City: effect of accelerated ageing on lung function and structure
Authors: Buendía-Roldan Ivette , Fernández-Plata Rosario , Valdes-Bartolo Abigail , Mejia Mayra , Jaramillo Luis E. , Martínez-Briseño David , Santiago-Ruiz Armando , Tapia-Aguilar Hugo , Gómez-Zamora Brenda , Pardo Annie , Selman Moises
Published: August 2020

Introduction

Phenotypic age better represents age-related biological dysregulation than chronological age. Recently, a multisystem-based ageing measure, which integrates chronological age and nine biomarkers, was proposed.

Methods

Phenotypic age was determined in 774 residents of Mexico City over 60 years old and without respiratory problems. We arbitrarily classified as “accelerated” ageing, those showing >4 years compared with their chronological age, and “slowed” ageing, those with <4 years compared with chronological age. Demographic risk factors were analysed with structured questionnaires. Lung structure was evaluated by high-resolution computed tomography and functional competence was analysed by forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), diffusion capacity of carbon monoxide (DLCO), and the 6-minute walk test (6MWT).

Results

Overall, 13% of this cohort showed accelerated ageing, which was corroborated with four independent biomarkers of ageing, 42% had normal ageing and 46% had slowed ageing. Risk factors associated with accelerated ageing were male sex (OR 4.4, 95% CI 2.4–7.9; p<0.01), diabetes mellitus (OR 9.7, 95% CI 5.5–17.2; p<0.01), and long-term sleep duration (OR 2.9 95% CI 1.34–6.35, p<0.01). Among smokers, there was a slight but significant association with the number of pack-years. Subjects with accelerated ageing showed decreased FVC (p<0.0001), FEV1(p<0.0001),DLCO(p<0.02) and walking distance in the 6MWT (p=0.0001). Slowed-ageing subjects presented less frequently with emphysematous lesions compared with those with accelerated ageing.

Conclusions

A small but significant proportion of residents of Mexico City age rapidly, which is associated with male sex, diabetes, and long-term sleep duration. They exhibit lower levels of lung function and develop emphysema more frequently.
Bioinformatics tools for marine biotechnology: a practical tutorial with a metagenomic approach
Authors: Liguori Ludovica , Monticelli Maria , Allocca Mariateresa , Cubellis Maria Vittoria , Hay Mele Bruno
Published: August 2020

Background

Bioinformatics has pervaded all fields of biology and has become an indispensable tool for almost all research projects. Although teaching bioinformatics has been incorporated in all traditional life science curricula, practical hands-on experiences in tight combination with wet-lab experiments are needed to motivate students.

Results

We present a tutorial that starts from a practical problem: finding novel enzymes from marine environments. First, we introduce the idea of metagenomics, a recent approach that extends biotechnology to non-culturable microbes. We presuppose that a probe for the screening of metagenomic cosmid library is needed. The students start from the chemical structure of the substrate that should be acted on by the novel enzyme and end with the sequence of the probe. To attain their goal, they discover databases such as BRENDA and programs such as BLAST and Clustal Omega.

Students’ answers to a satisfaction questionnaire show that a multistep tutorial integrated into a research wet-lab project is preferable to conventional lectures illustrating bioinformatics tools.

Conclusion

Experimental biologists can better operate basic bioinformatics if a problem-solving approach is chosen.
Clustering analysis of tumor metabolic networks
Authors: Manipur Ichcha , Granata Ilaria , Maddalena Lucia , Guarracino Mario R.
Published: August 2020

Background

Biological networks are representative of the diverse molecular interactions that occur within cells. Some of the commonly studied biological networks are modeled through protein-protein interactions, gene regulatory, and metabolic pathways. Among these, metabolic networks are probably the most studied, as they directly influence all physiological processes. Exploration of biochemical pathways using multigraph representation is important in understanding complex regulatory mechanisms. Feature extraction and clustering of these networks enable grouping of samples obtained from different biological specimens. Clustering techniques separate networks depending on their mutual similarity.

Results

We present a clustering analysis on tissue-specific metabolic networks for single samples from three primary tumor sites: breast, lung, and kidney cancer. The metabolic networks were obtained by integrating genome scale metabolic models with gene expression data. We performed network simplification to reduce the computational time needed for the computation of network distances. We empirically proved that networks clustering can characterize groups of patients in multiple conditions.

Conclusions

We provide a computational methodology to explore and characterize the metabolic landscape of tumors, thus providing a general methodology to integrate analytic metabolic models with gene expression data. This method represents a first attempt in clustering large scale metabolic networks. Moreover, this approach gives the possibility to get valuable information on what are the effects of different conditions on the overall metabolism.
ELIXIR-IT HPC@CINECA: high performance computing resources for the bioinformatics community
Authors: Castrignanò Tiziana , Gioiosa Silvia , Flati Tiziano , Cestari Mirko , Picardi Ernesto , Chiara Matteo , Fratelli Maddalena , Amente Stefano , Cirilli Marco , Tangaro Marco Antonio , Chillemi Giovanni , Pesole Graziano , Zambelli Federico
Published: August 2020

Background

The advent of Next Generation Sequencing (NGS) technologies and the concomitant reduction in sequencing costs allows unprecedented high throughput profiling of biological systems in a cost-efficient manner. Modern biological experiments are increasingly becoming both data and computationally intensive and the wealth of publicly available biological data is introducing bioinformatics into the “Big Data” era. For these reasons, the effective application of High Performance Computing (HPC) architectures is becoming progressively more recognized also by bioinformaticians.

Here we describe HPC resources provisioning pilot programs dedicated to bioinformaticians, run by the Italian Node of ELIXIR (ELIXIR-IT) in collaboration with CINECA, the main Italian supercomputing center.

Results

Starting from April 2016, CINECA and ELIXIR-IT launched the pilot Call “ELIXIR-IT HPC@CINECA”, offering streamlined access to HPC resources for bioinformatics. Resources are made available either through web front-ends to dedicated workflows developed at CINECA or by providing direct access to the High Performance Computing systems through a standard command-line interface tailored for bioinformatics data analysis. This allows to offer to the biomedical research community a production scale environment, continuously updated with the latest available versions of publicly available reference datasets and bioinformatic tools. Currently, 63 research projects have gained access to the HPC@CINECA program, for a total handout of ~ 8 Millions of CPU/hours and, for data storage, ~ 100 TB of permanent and ~ 300 TB of temporary space.

Conclusions

Three years after the beginning of the ELIXIR-IT HPC@CINECA program, we can appreciate its impact over the Italian bioinformatics community and draw some considerations. Several Italian researchers who applied to the program have gained access to one of the top-ranking public scientific supercomputing facilities in Europe. Those investigators had the opportunity to sensibly reduce computational turnaround times in their research projects and to process massive amounts of data, pursuing research approaches that would have been otherwise difficult or impossible to undertake. Moreover, by taking advantage of the wealth of documentation and training material provided by CINECA, participants had the opportunity to improve their skills in the usage of HPC systems and be better positioned to apply to similar EU programs of greater scale, such as PRACE. To illustrate the effective usage and impact of the resources awarded by the program - in different research applications - we report five successful use cases, which have already published their findings in peer-reviewed journals.
Postoperative outcomes of kidney transplant recipients undergoing non-transplant-related elective surgery: a systematic review and meta-analysis
Authors: Palamuthusingam Dharmenaan , Kunarajah Kuhan , Pascoe Elaine M. , Johnson David W. , Hawley Camel M. , Fahim Magid
Published: August 2020

Background

Reliable estimates of the absolute and relative risks of postoperative complications in kidney transplant recipients undergoing elective surgery are needed to inform clinical practice. This systematic review and meta-analysis aimed to estimate the odds of both fatal and non-fatal postoperative outcomes in kidney transplant recipients following elective surgery compared to non-transplanted patients.

Methods

Systematic searches were performed through Embase and MEDLINE databases to identify relevant studies from inception to January 2020. Risk of bias was assessed by the Newcastle Ottawa Scale and quality of evidence was summarised in accordance with GRADE methodology (grading of recommendations, assessment, development and evaluation). Random effects meta-analysis was performed to derive summary risk estimates of outcomes. Meta-regression and sensitivity analyses were performed to explore heterogeneity.

Results

Fourteen studies involving 14,427 kidney transplant patients were eligible for inclusion. Kidney transplant recipients had increased odds of postoperative mortality; cardiac surgery (OR 2.2, 95%CI 1.9–2.5), general surgery (OR 2.2, 95% CI 1.3–4.0) compared to non-transplanted patients. The magnitude of the mortality odds was increased in the presence of diabetes mellitus. Acute kidney injury was the most frequently reported non-fatal complication whereby kidney transplant recipients had increased odds compared to their non-transplanted counterparts. The odds for acute kidney injury was highest following orthopaedic surgery (OR 15.3, 95% CI 3.9–59.4). However, there was no difference in the odds of stroke and pneumonia.

Conclusion

Kidney transplant recipients are at increased odds for postoperative mortality and acute kidney injury following elective surgery. This review also highlights the urgent need for further studies to better inform perioperative risk assessment to assist in planning perioperative care.
Working conditions of healthcare workers and clients’ satisfaction with care: study protocol and baseline results of a cluster-randomised workplace intervention
Authors: Montano Diego , Kuchenbaur Marco , Geissler Heinrich , Peter Richard
Published: August 2020

Background

In the present investigation the study protocol and the results at baseline of a workplace intervention are reported. It is hypothesised that the reduction of the physical and psychosocial workload of healthcare workers increases 1 their self-assessed physical and mental work ability, and 2. clients’ satisfaction with care.

Methods

Two-arm, cluster-randomised trial. Outcome data on workers and clients are collected in questionnaires at baseline, and two follow-ups between 2019 and 2021. Participants of the interventions are healthcare workers of 11 healthcare providers in Germany. At baseline, the intervention arm comprised 22 clusters (n = 174 workers); the control arm, 47 clusters (n = 276). The intervention consists of interviews and workshops, in which employees propose measures aiming to reduce the physical and psychosocial load, and strengthen resources at work. The primary outcome is the workers’ physical and mental work ability. The secondary outcome is the clients’ satisfaction with care.

Results

There was no evidence of substantial differences between trial arms at baseline concerning the outcomes. The design effect estimates for physical and mental work ability were 1.29 and 1.05, respectively. At the end of the trial, effect sizes of at least 0.30 and 0.27 at the 80% power and 5% significance levels can be attained.

Conclusions

The results suggest that the implementation of the study design has been satisfactory. The intervention is expected to provide evidence of relatively small to medium-size effects of the intervention activities on the work ability of healthcare workers and the clients’ satisfaction with care.

Trial registration

Registration trial DRKS00021138 on the German Registry of Clinical Studies (DRKS), retrospectively registered on 25 March, 2020.
Historical trends in breast Cancer among women in China from age-period-cohort modeling of the 1990–2015 breast Cancer mortality data
Authors: Ding Yani , Chen Xinguang , Zhang Qingjun , Liu Qing
Published: August 2020

Background

Evidence on historical trends extracted embedded in recent data can advance our understanding of the epidemiology of breast cancer for Chinese women. China is a country with significant political, socioeconomic, and cultural events since the 1900s; however, no such studies are reported in the literature.

Methods

Age-specific mortality rates of breast cancer during 1990–2015 in China were analyzed using APC modeling (age-period-cohort modeling) method. Net effect from birth cohort was derived to measure cancer mortality risk during 1906–1990 when no mortality data were collected, and net effect from time period was derived to measure cancer mortality risk during 1990–2015 when data were collected. Model parameters were estimated using intrinsic estimator, a novel method to handle collinearity. The estimated effects were numerical differentiated to enhance presentations of time/age trend.

Results

Breast cancer mortality rate per 100,000 women increased from 6.83 in 1990 to 12.07 in 2015. After controlling for age and period, the risk of breast cancer mortality declined from 0.626 in 1906–10 to − 1.752 in 1991–95 (RR = 0.09). The decline consisted of 3 phases, a gradual phase during 1906–1940, a moderate phase with some fluctuations during 1941–1970, and a rapid phase with large fluctuations during 1971–1995. After controlling for age and cohort, the risk of breast cancer mortality increased from − 0.141 in 1990 to 0.258 in 2015 (RR = 1.49) with an acceleration after 2005. The time trends revealed by both the cohort effect and the period effect were in consistency with the significant political and socioeconomic events in China since the 1900s.

Conclusions

With recent mortality data in 1990–2015, we detected the risk of breast cancer mortality for Chinese women over a long period from 1906 to 2015. The risk declined more than 90% from the highest level in 1906–10 to the lowest in 1990–95, followed by an increase of 49% from 1990 to 2015. Findings of this study connected historical evidence with recent data, supporting further research to exam the relationship between development and risk of breast cancer for medical and health decision-making at the population level and prevention and treatment at the individual level.
Safety studies and viral shedding of intramuscular administration of oncolytic vaccinia virus TG6002 in healthy beagle dogs
Authors: Béguin Jérémy , Nourtier Virginie , Gantzer Murielle , Cochin Sandrine , Foloppe Johann , Balloul Jean-Marc , Laloy Eve , Tierny Dominique , Klonjkowski Bernard , Quemeneur Eric , Maurey Christelle , Erbs Philippe
Published: August 2020

Background

Cancer is a leading cause of mortality for both humans and dogs. As spontaneous canine cancers appear to be relevant models of human cancers, developing new therapeutic approaches could benefit both species. Oncolytic virotherapy is a promising therapeutic approach in cancer treatment. TG6002 is a recombinant oncolytic vaccinia virus deleted in the thymidine kinase and ribonucleotide reductase genes and armed with the suicide gene FCU1 that encodes a protein which catalyses the conversion of the non-toxic 5-fluorocytosine into the toxic metabolite 5-fluorouracil. Previous studies have shown the ability of TG6002 to infect and replicate in canine tumor cell lines, and demonstrated its oncolytic potency in cell lines, xenograft models and canine mammary adenocarcinoma explants. Moreover, 5-fluorouracil synthesis has been confirmed in fresh canine mammary adenocarcinoma explants infected with TG6002 with 5-fluorocytosine. This study aims at assessing the safety profile and viral shedding after unique or repeated intramuscular injections of TG6002 in seven healthy Beagle dogs.

Results

Repeated intramuscular administrations of TG6002 at the dose of 5 × 107 PFU/kg resulted in no clinical or biological adverse effects. Residual TG6002 in blood, saliva, urine and feces of treated dogs was not detected by infectious titer assay nor by qPCR, ensuring the safety of the virus in the dogs and their environment.

Conclusions

These results establish the good tolerability of TG6002 in healthy dogs with undetectable viral shedding after multiple injections. This study supports the initiation of further studies in canine cancer patients to evaluate the oncolytic potential of TG6002 and provides critical data for clinical development of TG6002 as a human cancer therapy.
A novel two-step, direct-to-PCR method for virus detection off swabs using human coronavirus 229E
Authors: Morehouse Zachary P. , Proctor Caleb M. , Ryan Gabriella L. , Nash Rodney J.
Published: August 2020

Background

Currently, one of the most reliable methods for viral infection detection are polymerase chain reaction (PCR) based assays. This process is time and resource heavy, requiring multiple steps of lysis, extraction, purification, and amplification procedures. Herein, we have developed a method to detect virus off swabs using solely shaker-mill based mechanical lysis and the transfer of the viral lysate directly to a PCR assay for virus detection, bypassing the substantial reagent and time investments required for extraction and purification steps.

Methods

Using Human Coronavirus 229E (HCoV-229E) as a model system, we spiked swabs in vitro for proof-of-concept testing. Swabs were spiked in serial dilutions from 1.2 × 106 to 1.2 × 101 copies/mL and then placed in 2 mL tubes with viral transport media (VTM) to mimic the specimen collection procedures in the clinic prior to processing via shaker-mill homogenization. After homogenization, 1 μL of lysate was processed using RT-qPCR for amplification of the nucleocapsid (N) gene, qualifying viral detection.

Results

HCoV-229E in vitro spiked swabs were processed in a novel two-step, direct-to-PCR methodology for viral detection. After running 54 swabs, we confidently determined our limit of detection to be 1.2 × 103 viral copies/mL with 96.30% sensitivity.

Conclusion

We have proven that the shaker-mill homogenization-based two-step, direct-to-PCR procedures provides sufficient viral lysis off swabs, where the resulting lysate can be used directly in PCR for the detection of HCoV-229E. This finding allows for reductions in the time and resources required for PCR based virus detection in comparison to the traditional extraction-to-PCR methodology.
Clinical application of chromosomal microarray analysis for fetuses with craniofacial malformations
Authors: Xu Chenyang , Xiang Yanbao , Xu Xueqin , Zhou Lili , Li Huanzheng , Dong Xueqin , Tang Shaohua
Published: August 2020

Background

The potential correlations between chromosomal abnormalities and craniofacial malformations (CFMs) remain a challenge in prenatal diagnosis. This study aimed to evaluate 118 fetuses with CFMs by applying chromosomal microarray analysis (CMA) and G-banded chromosome analysis.

Results

Of the 118 cases in this study, 39.8% were isolated CFMs (47/118) whereas 60.2% were non-isolated CFMs (71/118). The detection rate of chromosomal abnormalities in non-isolated CFM fetuses was significantly higher than that in isolated CFM fetuses (26/71 vs. 7/47, p = 0.01). Compared to the 16 fetuses (16/104; 15.4%) with pathogenic chromosomal abnormalities detected by karyotype analysis, CMA identified a total of 33 fetuses (33/118; 28.0%) with clinically significant findings. These 33 fetuses included cases with aneuploidy abnormalities (14/118; 11.9%), microdeletion/microduplication syndromes (9/118; 7.6%), and other pathogenic copy number variations (CNVs) only (10/118; 8.5%).We further explored the CNV/phenotype correlation and found a series of clear or suspected dosage-sensitive CFM genes including TBX1, MAPK1, PCYT1A, DLG1, LHX1, SHH, SF3B4, FOXC1, ZIC2, CREBBP, SNRPB, and CSNK2A1.

Conclusion

These findings enrich our understanding of the potential causative CNVs and genes in CFMs. Identification of the genetic basis of CFMs contributes to our understanding of their pathogenesis and allows detailed genetic counselling.
Author Correction: SMURF-seq: efficient copy number profiling on long-read sequencers
Authors: Prabakar Rishvanth K. , Xu Liya , Hicks James , Smith Andrew D.
Published: August 2020

An amendment to this paper has been published and can be accessed via the original article.
Protein delivery in intermittent and continuous enteral nutrition with a protein-rich formula in critically ill patients—a protocol for the prospective randomized controlled proof-of-concept Protein Bolus Nutrition (Pro BoNo) study
Authors: Reinhold Simona , Yeginsoy Desirée , Hollinger Alexa , Todorov Atanas , Tintignac Lionel , Sinnreich Michael , Kiss Caroline , Gebhard Caroline E. , Kovács Balázs , Gysi Bianca , Imwinkelried Lara , Siegemund Martin
Published: August 2020

Background

Critically ill patients rapidly develop muscle wasting resulting in sarcopenia, long-term disability and higher mortality. Bolus nutrition (30–60 min period), whilst having a similar incidence of aspiration as continuous feeding, seems to provide metabolic benefits through increased muscle protein synthesis due to higher leucine peaks.

To date, clinical evidence on achievement of nutritional goals and influence of bolus nutrition on skeletal muscle metabolism in ICU patients is lacking. The aim of the Pro BoNo study (Protein Bolus Nutrition) is to compare intermittent and continuous enteral feeding with a specific high-protein formula. We hypothesise that target quantity of protein is reached earlier (within 36 h) by an intermittent feeding protocol with a favourable influence on muscle protein synthesis.

Methods

Pro BoNo is a prospective randomised controlled study aiming to compare the impact of intermittent and continuous enteral feeding on preventing muscle wasting in 60 critically ill patients recruited during the first 48 h after ICU admission. The primary outcome measure is the time until the daily protein target (≥ 1.5 g protein/kg bodyweight/24 h) is achieved. Secondary outcome measures include tolerance of enteral feeding and evolution of glucose, urea and IGF-1. Ultrasound and muscle biopsy of the quadriceps will be performed.

Discussion

The Basel Pro BoNo study aims to collect innovative data on the effect of intermittent enteral feeding of critically ill patients on muscle wasting.

Trial registration

ClinicalTrials.govNCT03587870. Registered on July 16, 2018. Swiss National Clinical Trials Portal SNCTP000003234. Last updated on July 24, 2019.
Lower peripheral helper T cell levels in the synovium are associated with a better response to anti-TNF therapy in rheumatoid arthritis
Authors: Julià Antonio , Ávila Gabriela , Celis Raquel , Sanmartí Raimon , Ramírez Julio , Marsal Sara , Cañete Juan D.
Published: August 2020

Background

The mechanisms by which only some rheumatoid arthritis (RA) patients respond favorably to TNF blockade are still poorly characterized. The goal of this study was to identify biological features that explain this differential response using a multilevel transcriptome analysis of the synovial membrane.

Methods

Synovial samples from 11 patients on anti-TNF therapy were obtained by arthroscopy at baseline and week 20. Analysis of the synovial transcriptome was performed at the gene, pathway, and cell-type levels. Newly characterized pathogenic cell types in RA, peripheral helper T cells (TPH), and CD34-THY1+ fibroblasts were estimated using a cell-type deconvolution approach. TPHassociation was validated using immunofluorescence. External validation was performed on an independent dataset.

Results

After multiple-test correction, 16 and 4 genes were differentially expressed at baseline and week 20, respectively. At the pathway level, 86 and 17 biological processes were significantly enriched at baseline and week 20, respectively. Longitudinal expression changes were associated with a drastic decrease of innate immune activity (P < 5e−30), and an activation of the bone and cartilage regeneration processes (P < 5e−10). Cell-type deconvolution revealed a significant association between low TPHcells at baseline and a better response (P = 0.026). Lower TPHcells were maintained in good responders up to week 20 (P = 0.032). Immunofluorescent analyses confirmed the accuracy of the cell-type estimation (r2 = 0.58,P = 0.005) and an association with response. TPHassociation with anti-TNF response was validated in an independent sample of RA patients (P = 0.0040).

Conclusions

A lower abundance in the synovial membrane of the pathogenic T cell type newly associated with RA, peripheral helper T lymphocyte, is associated with a good response to anti-TNF therapy. Major changes in the myeloid cell compartment were also observed in response to therapy. The results of this study could help develop more effective therapies aimed at treating the pathogenic mechanisms in RA that are currently not well targeted by anti-TNF agents.
Furosemide and spironolactone doses and hyponatremia in patients with heart failure
Authors: Velat Ivan , Bušić Željko , Jurić Paić Marina , Čulić Viktor
Published: August 2020

Background

Hyponatremia, a marker of disease severity and prognosis, has been associated with various clinical factors and drug use, especially diuretics.

Methods

This observational prospective cohort study enrolled patients hospitalized at the University Hospital Center Split because of heart failure (HF). We investigated the association of clinical variables and cardiovascular drugs, including furosemide, hydrochlorothiazide, spironolactone, and their doses, with the presence of hyponatremia at admission.

Results

Of the 565 included patients, 32.4% were hyponatremic, 62.6% were males, and the mean age was 73.1 ± 10.6 years. In the univariate analysis, hyponatremic patients were more often current smokers (p = 0.01), alcohol consumers (p = 0.01), receiving spironolactone (p = 0.004) or combination of furosemide and spironolactone (p = 0.003). Patients who received 50 and 100 mg of spironolactone, compared to those receiving 25 mg (p < 0.0001), as well as patients who received 250 to 500 mg of furosemide compared to ≤240 mg (p = 0.001), were significantly more often hyponatremic. In the multivariate analysis, when diuretic doses were accounted for, furosemide doses of 250 to 500 mg (p = 0.009), spironolactone doses of 50 to 100 mg (p = 0.0003), increasing age (p = 0.03), diabetes mellitus (p = 0.02) and alcohol consumption (p = 0.04) were independently associated with hyponatremia.

Conclusion

High doses of furosemide and spironolactone, or concomitant use of these diuretics, seem to be an important cause of hyponatremia in HF patients, particularly in combination with advanced age, diabetes and alcohol consumption. Diuretic dose reduction may help avoid hyponatremia and improve clinical status and prognosis in such patients.
New somatic TERT promoter variants enhance the Telomerase activity in Glioblastoma
Authors: Pierini Tiziana , Nardelli Carlotta , Lema Fernandez Anair Graciela , Pierini Valentina , Pellanera Fabrizia , Nofrini Valeria , Gorello Paolo , Moretti Martina , Arniani Silvia , Roti Giovanni , Giovenali Paolo , Lupattelli Marco , Metro Giulio , Molica Carmen , Castrioto Corrado , Corinaldesi Rodolfo , Laurenti Maria Elena , Ascani Stefano , Mecucci Cristina , La Starza Roberta
Published: August 2020

The catalytic activity of human Telomerase Reverse Transcriptase (TERT) compensates for the loss of telomere length, eroded during each cell cycle, to ensure a correct division of stem and germinal cells. In human tumors, ectopic TERT reactivation, most frequently due to hotspot mutations in the promoter region (TERTp), i.e. c.1-124 C > T, c.1-146 C > T, confers a proliferative advantage to neoplastic cells. In gliomas, TERTp mutations (TERTpmut) mainly occur in oligodendroglioma and glioblastoma. We screened, for TERTp hotspot mutations, 301 adult patients with gliomas and identified heterozygous mutations in 239 cases: 94% of oligodendroglioma, 85% of glioblastoma, and 37.5% of diffuse/anaplastic astrocytoma. Besides the recurrent c.1-124 C > T and c.1-146 C > T, two cases of glioblastoma harbored novel somatic TERTp variants, which consisted of a tandem duplications of 22 nucleotides, i.e. a TERTp c.1-100_1-79dup and TERTp c.1-110_1-89, both located downstream c.1-124 C > T and c.1-146 C > T. In silico analysis predicted the formation of 119 and 108 new transcription factor’s recognition sites for TERTp c.1-100_1-79dup and TERTp c.1-110_1-89, respectively. TERTp duplications (TERTpdup) mainly affected the binding capacity of two transcription factors’ families, i.e. the members of the E-twenty-six and the Specificity Protein/Krüppel-Like Factor groups. In fact, these new TERTpdup significantly enhanced the E-twenty-six transcription factors’ binding capacity, which is also typically increased by the two c.1-124 C > T/c.1-146 C > T hotspot TERTpmut. On the other hand, they were distinguished by enhanced affinity for the Krüppel proteins. The luciferase assay confirmed that TERTpdup behaved as gain-of-function mutations causing a 2,3-2,5 fold increase of TERT transcription. The present study provides new insights into TERTp mutational spectrum occurring in central nervous system tumors, with the identification of new recurrent somatic gain-of-function mutations, occurring in 0.8% of glioblastoma IDH-wildtype.
Aluminum tanning of hide powder and skin pieces under microwave irradiation
Authors: Liu Yue , Song Bin , Zhang Jinwei , Gaidau Carmen , Gu Haibin
Published: August 2020

The application and mechanism study of microwave irradiation in traditional industries have attracted considerable attention owing to the unique thermal and athermal effects that could lead to unexpected benefits in high-efficiency and clean production. Herein, we report the investigation of the aluminum tanning under microwave irradiation upon using hide powder and skin pieces, respectively, as simulants of real hide or skin. The aluminum tanning process and the tanned products under microwave heating (MWH) were studied and compared with those of conventional water bath heating (WBH) as the controls. For the tanning system of hide powder, the tanning effluents were analyzed in terms of pH, conductivity, dielectric constant and aluminum content, and the tanned powder was investigated by differential scanning calorimetry (DSC), thermogravimetric (TG) analysis, and FT-IR spectroscopy. For the skin piece system, the pH and aluminum content of tanning effluents were also determined, and at the same time, DSC, TG, SEM, FT-IR and shrinkage temperature were used to illustrate the actions of microwaves on the structure and properties of the tanned pieces. The results show that aluminum reactivity in the penetration and binding process of collagen fibers in hide powder and skin pieces improved using microwave treatment. The residual aluminum content was greatly reduced by microwave heating action, and the increased amount of aluminum with evener distribution was observed in the tanned products. Microwave irradiation also resulted in the tanned products with better thermal stability and thermal decomposition resistance. This work further promotes application of microwave treatments for aluminum-based tanning in leather industry.

Graphical abstract