bluuebunny/crossref_metadata_2025 huggingface dataset:
The alveolar epithelial cells are involved in pulmonary vascular remodeling and constriction of hypoxic pulmonary hypertension
Authors: Wang Yanxia , Li Xiaoming , Niu Wen , Chen Jian , Zhang Bo , Zhang Xiumin , Wang Yingmei , Dang Shaokang , Li Zhichao
Published: May 2021

Background

Hypoxic pulmonary hypertension (HPH) is a common type of pulmonary hypertension and characterized by pulmonary vascular remodeling and constriction. Alveolar epithelial cells (AECs) primarily sense alveolar hypoxia, but the role of AECs in HPH remains unclear. In this study, we explored whether AECs are involved in pulmonary vascular remodeling and constriction.

Methods

In the constructed rat HPH model, hemodynamic and morphological characteristics were measured. By treating AECs with hypoxia, we further detected the levels of superoxide dismutase 2 (SOD2), catalase (CAT), reactive oxygen species (ROS) and hydrogen peroxide (H2O2), respectively. To detect the effects of AECs on pulmonary vascular remodeling and constriction, AECs and pulmonary artery smooth cells (PASMCs) were co-cultured under hypoxia, and PASMCs and isolated pulmonary artery (PA) were treated with AECs hypoxic culture medium. In addition, to explore the mechanism of AECs on pulmonary vascular remodeling and constriction, ROS inhibitor N-acetylcysteine (NAC) was used.

Results

Hypoxia caused pulmonary vascular remodeling and increased pulmonary artery pressure, but had little effect on non-pulmonary vessels in vivo. Meanwhile, in vitro, hypoxia promoted the imbalance of SOD2 and CAT in AECs, leading to increased ROS and hydrogen peroxide (H2O2) production in the AECs culture medium. In addition, AECs caused the proliferation of co-cultured PASMCs under hypoxia, and the hypoxic culture medium of AECs enhanced the constriction of isolated PA. However, treatment with ROS inhibitor NAC effectively alleviated the above effects.

Conclusion

The findings of present study demonstrated that AECs were involved in pulmonary vascular remodeling and constriction under hypoxia by paracrine H2O2into the pulmonary vascular microenvironment.
Comparative outcomes in patients receiving pirfenidone or nintedanib for idiopathic pulmonary fibrosis
Authors: Belhassen Manon , Dalon Faustine , Nolin Maëva , Van Ganse Eric
Published: May 2021

Background

Real-world data regarding outcomes of idiopathic pulmonary fibrosis (IPF) are scarce, outside of registries. In France, pirfenidone and nintedanib are only reimbursed for documented IPF, with similar reimbursement criteria with respect to disease characteristics, prescription through a dedicated form, and IPF diagnosis established in multidisciplinary discussion.

Research question

The data of the comprehensive French National Health System were used to evaluate outcomes in patients newly treated with pirfenidone or nintedanib in 2015–2016.

Study design and methods

Patients aged < 50 years or who had pulmonary fibrosis secondary to an identified cause were excluded. All-cause mortality, acute respiratory-related hospitalisations and treatment discontinuations up to 31 December 2017 were compared using a Cox proportional hazards model adjusted for age, sex, year of treatment initiation, time to treatment initiation and proxies of disease severity identified during a pre-treatment period.

Results

During the study period, a treatment with pirfenidone or nintedanib was newly initiated in 804 and 509 patients, respectively. No difference was found between groups for age, sex, time to treatment initiation, Charlson comorbidity score, and number of hospitalisations or medical contacts prior to treatment initiation. As compared to pirfenidone, nintedanib was associated with a greater risk of all-cause mortality (hazard ratio [HR], 1.8; 95% confidence interval [CI] 1.3–2.6), a greater risk of acute respiratory-related hospitalisations (HR 1.3; 95% CI 1.0–1.7) and a lower risk of treatment discontinuation at 12 months (HR 0.7; 95% CI 0.6–0.9).

Interpretation

This observational study identified potential differences in outcome under newly prescribed antifibrotic drugs, deserving further explorations.
Pals1 prevents Rac1-dependent colorectal cancer cell metastasis by inhibiting Arf6
Authors: Lüttgenau Simona Mareike , Emming Christin , Wagner Thomas , Harms Julia , Guske Justine , Weber Katrin , Neugebauer Ute , Schröter Rita , Panichkina Olga , Pethő Zoltán , Weber Florian , Schwab Albrecht , Wege Anja Kathrin , Nedvetsky Pavel , Krahn Michael P.
Published: May 2021

Loss of apical-basal polarity and downregulation of cell-cell contacts is a critical step during the pathogenesis of cancer. Both processes are regulated by the scaffolding protein Pals1, however, it is unclear whether the expression of Pals1 is affected in cancer cells and whether Pals1 is implicated in the pathogenesis of the disease.

Using mRNA expression data and immunostainings of cancer specimen, we show that Pals1 is frequently downregulated in colorectal cancer, correlating with poorer survival of patients. We further found that Pals1 prevents cancer cell metastasis by controlling Rac1-dependent cell migration through inhibition of Arf6, which is independent of the canonical binding partners of Pals1. Loss of Pals1 in colorectal cancer cells results in increased Arf6 and Rac1 activity, enhanced cell migration and invasion in vitro and increased metastasis of transplanted tumor cells in mice. Thus, our data reveal a new function of Pals1 as a key inhibitor of cell migration and metastasis of colorectal cancer cells. Notably, this new function is independent of the known role of Pals1 in tight junction formation and apical-basal polarity.
Inequality of weight status in urban Cuba: 2001–2010
Authors: Nie Peng , Ding Lanlin , Sousa-Poza Alfonso , Leon Alina Alfonso , Xue Hong , Jia Peng , Wang Liang , Wang Youfa
Published: May 2021

Background

Although understanding changes in the body weight distribution and trends in obesity inequality plays a key role in assessing the causes and persistence of obesity, limited research on this topic is available for Cuba. This study thus analyzed changes in body mass index (BMI) and waist circumference (WC) distributions and obesity inequality over a 9-year period among urban Cuban adults.

Methods

Kolmogorov-Smirnov tests were first applied to the data from the 2001 and 2010 National Survey on Risk Factors and Chronic Diseases to identify a rightward shift in both the BMI and WC distributions over the 2001–2010 period. A Shapley technique decomposed the increase in obesity prevalence into a mean-growth effect and a (re)distributional component. A univariate assessment of obesity inequality was then derived by calculating both the Gini and generalized entropy (GE) measures. Lastly, a GE-based decomposition partitioned overall obesity inequality into within-group and between-group values.

Results

Despite some relatively pronounced left-skewing, both the BMI and WC distributions exhibited a clear rightward shift to which the increases in general and central obesity can be mostly attributed. According to the Gini coefficients, both general and central obesity inequality increased over the 2001–2010 period, from 0.105 [95% confidence interval (CI) = 0.103–0.106] to 0.110 [95% CI = 0.107–0.112] and from 0.083 [95% CI = 0.082–0.084] to 0.085 [95% CI = 0.084–0.087], respectively. The GE-based decomposition further revealed that both types of inequality were accounted for primarily by within-group inequality (93.3%/89.6% and 87.5%/84.8% in 2001/2010 for general/central obesity, respectively).

Conclusions

Obesity inequality in urban Cuba worsened over the 2001–2010 time period, with within-group inequality in overall obesity dominant over between-group inequality. In general, the results also imply that the rise in obesity inequality is immune to health care system characteristics.
Estimating causes of out-of-hospital deaths in China: application of SmartVA methods
Authors: Qi Jinlei , Adair Tim , Chowdhury Hafizur R. , Li Hang , McLaughlin Deirdre , Liu Yunning , Liu Jiangmei , Zeng Xinying , You Jinling , Firth Sonja , Sorchik Renee , Yin Peng , Wang Lijun , Zhou Maigeng , Lopez Alan D.
Published: May 2021

Background

Most deaths in China occur at home, making it difficult to collect reliable cause of death (CoD) information. Verbal autopsy (VA) was applied using the SmartVA tool to a sample of home deaths in China to explore its feasibility as a means of improving the quality of CoD data.

Methods

The study was carried out in 22 districts in 9 provinces, located in north-east, central, and western areas of China during 2017 and 2018. Trained interviewers selected suitable respondents in each household to collect information using the Population Health Metrics Research Consortium (PHMRC) shortened and validated electronic VA questionnaire on tablets. The CoD was diagnosed from the interview data using the SmartVA-Analyze 2.0 software (Tariff 2.0).

Results

Non-communicable diseases (NCDs) dominated the leading causes of death in all age groups and for both sexes. After redistribution of undetermined causes, stroke (24%), ischemic heart diseases (IHD) (21%), chronic respiratory diseases (11%), and lung cancer (6%) were the leading causes of death. The cause fractions for level-one cause categories and ranking of specific causes were similar between SmartVA and results from the Global Burden of Disease (GBD) study.

Conclusion

Evidence from this large pilot study suggests that SmartVA is a feasible and plausible tool and could be a valuable tool to improve the quality and standardization of CoD information across China.
Impact of mixed meal tolerance test composition on measures of beta-cell function in type 2 diabetes
Authors: Kössler Theresa , Bobrov Pavel , Strassburger Klaus , Kuss Oliver , Zaharia Oana-Patricia , Karusheva Yanislava , Möser Clara , Bódis Kálmán , Burkart Volker , Roden Michael , Szendroedi Julia ,   for the GDS Group, Roden M. , Al-Hasani H. , Belgardt B. , Burkart V. , Buyken A. E. , Geerling G. , Herder C. , Hwang J. H. , Icks A. , Jandeleit-Dahm K. , Kahl S. , Kotzka J. , Kuß O. , Lammert E. , Rathmann W. , Szendroedi J. , Trenkamp S. , Ziegler D.
Published: May 2021

Background

Application of mixed meal tolerance tests (MMTT) to measure beta-cell function in long-term studies is limited by modification of the commercial products occurring over time. This study assessed the intra-individual reliability of MMTTs and compared the effects of liquid meals differing in macronutrient composition on the estimation of beta-cell function in type 2 diabetes (T2DM).

Methods

To test the reliability of MMTTs, 10 people with T2DM (age 58 ± 11 years, body mass index 30.0 ± 4.9 kg/m2) received Boost®high Protein 20 g protein three times. For comparing different meals, another 10 persons with T2DM (58 ± 5 years, 31.9 ± 5.3 kg/m2) ingested either Boost®high Protein 20 g protein or the isocaloric Boost®high Protein 15 g protein containing 35% less protein and 18% more carbohydrates. C-peptide, insulin and glucose release were assessed from the incremental area under the concentration time curve (iAUC) and the intra- and inter-individual variation of these parameters from the coefficients of variations (CV).

Results

Repetitive ingestion of one meal revealed intra-individual CVs for the iAUCs of C-peptide, insulin and glucose, which were at least 3-times lower than the inter-individual variation of these parameters (18.2%, 19.7% and 18.9% vs. 74.2%, 70.5% and 207.7%) indicating a good reliability. Ingestion of two different meals resulted in comparable intra-individual CVs of the iAUCs of C-peptide and insulin (16.9%, 20.5%).

Conclusion

MMTTs provide reliable estimation of beta-cell function in people with T2DM. Furthermore, moderate differences in the protein and carbohydrate contents in a standardized liquid meal do not result in relevant changes of C-peptide and insulin responses.

Trial registration: Clinicaltrials.gov, Identifier number: NCT01055093. Registered 22 January 2010 – Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/study/NCT01055093
Convalescent plasma for adults with acute COVID-19 respiratory illness (CONCOR-1): study protocol for an international, multicentre, randomized, open-label trial
Authors: Bégin Philippe , Callum Jeannie , Heddle Nancy M. , Cook Richard , Zeller Michelle P. , Tinmouth Alan , Fergusson Dean A. , Cushing Melissa M. , Glesby Marshall J. , Chassé Michaël , Devine Dana V. , Robitalle Nancy , Bazin Renée , Shehata Nadine , Finzi Andrés , McGeer Allison , Scales Damon C. , Schwartz Lisa , Turgeon Alexis F. , Zarychanski Ryan , Daneman Nick , Carl Richard , Amorim Luiz , Gabe Caroline , Ellis Martin , Sachais Bruce S. , Loftsgard Kent Cadogan , Jamula Erin , Carruthers Julie , Duncan Joanne , Lucier Kayla , Li Na , Liu Yang , Armali Chantal , Kron Amie , Modi Dimpy , Auclair Marie-Christine , Cerro Sabrina , Avram Meda , Arnold Donald M.
Published: May 2021

Background

Convalescent plasma has been used for numerous viral diseases including influenza, severe acute respiratory syndrome, Middle East respiratory syndrome and Ebola virus; however, evidence to support its use is weak. SARS-CoV-2 is a novel coronavirus responsible for the 2019 global pandemic of COVID-19 community acquired pneumonia. We have undertaken a randomized controlled trial to assess the efficacy and safety of COVID-19 convalescent plasma (CCP) in patients with SARS-CoV-2 infection.

Methods

CONCOR-1 is an open-label, multicentre, randomized trial. Inclusion criteria include the following: patients > 16 years, admitted to hospital with COVID-19 infection, receiving supplemental oxygen for respiratory complications of COVID-19, and availability of blood group compatible CCP. Exclusion criteria are : onset of respiratory symptoms more than 12 days prior to randomization, intubated or imminent plan for intubation, and previous severe reactions to plasma. Consenting patients are randomized 2:1 to receive either approximately 500 mL of CCP or standard of care. CCP is collected from donors who have recovered from COVID-19 and who have detectable anti-SARS-CoV-2 antibodies quantified serologically. The primary outcome is intubation or death at day 30. Secondary outcomes include ventilator-free days, length of stay in intensive care or hospital, transfusion reactions, serious adverse events, and reduction in SARS-CoV-2 viral load. Exploratory analyses include patients who received CCP containing high titre antibodies. A sample size of 1200 patients gives 80% power to detect a 25% relative risk reduction assuming a 30% baseline risk of intubation or death at 30 days (two-sided test; α = 0.05). An interim analysis and sample size re-estimation will be done by an unblinded independent biostatistician after primary outcome data are available for 50% of the target recruitment (n = 600).

Discussion

This trial will determine whether CCP will reduce intubation or death non-intubated adults with COVID-19. The trial will also provide information on the role of and thresholds for SARS-CoV-2 antibody titres and neutralization assays for donor qualification.

Trial registration

Clinicaltrials.govNCT04348656. Registered on 16 April 2020.
Multidisciplinary corroboration in differentiation syndrome: a case report
Authors: Sarkar Sayan , Ghosh Priya , Gehani Anisha , Ghara Niharendu , Bhattacharyya Parthasarathi
Published: May 2021

Background

Differentiation syndrome (DS) is a life-threatening complication that may be seen in patients with acute promyelocytic leukaemia undergoing induction therapy with all-trans retinoic acid or arsenic trioxide. It can lead to severe inflammatory response syndrome and shock if adequate measures are not taken immediately. The radiological features of lung nodules with changes in ground-glass opacity can represent DS. The principal unique feature of the case reported here is that the diagnosis of DS was based on imaging results in the absence of a low total leukocyte count.

Case presentation

A 14-year-old Indian girl diagnosed with acute promyelocytic leukaemia currently undergoing a chemotherapy regimen that included all-trans retinoic acid/arsenic trioxide was sent to the radiology department for investigation of respiratory distress which she had developed soon after the initiation of chemotherapy. Her chest radiograph showed bilateral lower zone lung infiltrates. Computed tomography (CT) revealed changes in ground-glass opacity in the lower lobes with multiple lung nodules. Differential diagnosis included bacterial, viral or fungal infections, leukemic infiltrates, drug toxicity, pulmonary haemorrhage or leukostasis. She was started on dexamethasone immediately after stopping the chemotherapy with all-trans retinoic acid/arsenic trioxide and given ventilatory support. Her condition subsequently improved and her follow-up chest radiograph and CT scan showed a significant reduction of abnormal lung findings. Based on the clinical improvement and the resolution of findings on imaging following the withdrawal of all-trans retinoic acid/arsenic trioxide, we made the diagnosis of DS.

Conclusions

Though a rather unusual possibility, the treatment history of the patient enabled a rather crucial diagnosis in the nick of time and imaging played a pivotal role. This case further iterates the importance of keeping DS in mind when dealing with similar patients in the future.
Multi-base compressive sensing procedure with application to ECG signal reconstruction
Authors: Orovic Irena , Stanković Srdjan , Beko Marko
Published: May 2021

Standard compressive sensing (CS) scenario assumes a single sparsifying basis used to reconstruct the signals from a small set of incoherent measurements. However, in many cases, the signal cannot be sparsely represented using a single transformation. Particularly, in ECG signal analysis, each signal segment is specific in nature and reflects different physical phenomena. Hence, using the same transformation for all segments may be inappropriate for efficient analysis and reconstruction. Moreover, in the CS scenario, it would be necessary to combine different transforms to achieve compact signal support and to provide successful reconstruction from randomly under-sampled data. This work proposes a hybrid CS reconstruction algorithm that combines different transform basis, based on the concept of orthogonal matching pursuit. The performance of the proposed approach is verified experimentally using the combination of the Fourier and the Hermite transform on the real ECG signals.
CARAMEL: results on a secure architecture for connected and autonomous vehicles detecting GPS spoofing attacks
Authors: Vitale Christian , Piperigkos Nikos , Laoudias Christos , Ellinas Georgios , Casademont Jordi , Escrig Josep , Kloukiniotis Andreas , Lalos Aris S. , Moustakas Konstantinos , Diaz Rodriguez Rodrigo , Baños Daniel , Roqueta Crusats Gemma , Kapsalas Petros , Hofmann Klaus-Peter , Khodashenas Pouria Sayyad
Published: May 2021

The main goal of the H2020-CARAMEL project is to address the cybersecurity gaps introduced by the new technological domains adopted by modern vehicles applying, among others, advanced Artificial Intelligence and Machine Learning techniques. As a result, CARAMEL enhances the protection against threats related to automated driving, smart charging of Electric Vehicles, and communication among vehicles or between vehicles and the roadside infrastructure. This work focuses on the latter and presents the CARAMEL architecture aiming at assessing the integrity of the information transmitted by vehicles, as well as at improving the security and privacy of communication for connected and autonomous driving. The proposed architecture includes: (1) multi-radio access technology capabilities, with simultaneous 802.11p and LTE-Uu support, enabled by the connectivity infrastructure; (2) a MEC platform, where, among others, algorithms for detecting attacks are implemented; (3) an intelligent On-Board Unit with anti-hacking features inside the vehicle; (4) a Public Key Infrastructure that validates in real-time the integrity of vehicle’s data transmissions. As an indicative application, the interaction between the entities of the CARAMEL architecture is showcased in case of a GPS spoofing attack scenario. Adopted attack detection techniques exploit robust in-vehicle and cooperative approaches that do not rely on encrypted GPS signals, but only on measurements available in the CARAMEL architecture.
Architecture for integrating vertical customer’s programmability control of network functions and connectivity in a slice-as-a-service schema
Authors: Contreras Luis M. , Barguil Samier , Vilalta Ricard , López Victor
Published: May 2021

Network slicing will permit offering to vertical customers tailored end-to-end logical networks in an on-demand fashion, on top of a common telecom infrastructure, achieving a Slices-as-a-Service (SlaaS) business model. This is possible due to the progressive introduction of network softwarization techniques, such as programmability and virtualization, into existing operational networks, enabling dynamic and flexible provision of slices. Those vertical customers could require the control not only of the network functions composing the end-to-end service, but also of the connectivity among them, e.g., for influencing the paths for steering traffic among function instances. However, this can be problematic since decisions from one vertical customer can collide with decisions from others. One aspect not yet sufficiently investigated is how to permit vertical customers to jointly control the service functions and the underlay connectivity, in such a way that could operate the allocated slice as if it was actually a dedicated network entirely for them. This paper explores some architectural proposition in this respect illustrated with some potential use cases and it provides an example of the provision of SlaaS for a vertical customer.
Global classical solutions to the elastodynamic equations with damping
Authors: Liu Mengmeng , Lin Xueyun
Published: May 2021

In this paper, we show the global existence of classical solutions to the incompressible elastodynamics equations with a damping mechanism on the stress tensor in dimension three for sufficiently small initial data on periodic boxes, that is, with periodic boundary conditions. The approach is based on a time-weighted energy estimate, under the assumptions that the initial deformation tensor is a small perturbation around an equilibrium state and the initial data have some symmetry.
Factors that influence clinical efficacy of live biotherapeutic products
Authors: Pot Bruno , Vandenplas Yvan
Published: May 2021

Traditional probiotics are increasingly being used in a medical context. The use of these products as drugs is considerably different from the traditional use as food or food supplements, as, obviously, the target population is different (diseased versus healthy or at risk population). Besides the target population, also the regulatory context is different, mainly with respect to production, administration regime and type of clinical studies required. In this paper we will, besides the regulatory differences, focus on aspects that may impact the efficacy of a live biotherapeutic product (drug), especially in a clinical setting. The impact of the dosage seems to depend on the strain and the application and may follow some rationale. In contrast, information on the impact of the time of administration or diet, is often still lacking. The matrix and the use of protective measures may clearly have an impact on the survival and efficacy of the strain.
Synergistic action of the gut microbiota in environmental RNA interference in a leaf beetle
Authors: Xu Letian , Xu Shijing , Sun Liuwei , Zhang Yiqiu , Luo Jing , Bock Ralph , Zhang Jiang
Published: May 2021

Background

RNA interference (RNAi) has emerged as an efficient tool to control insect pests. When insects ingest double-stranded RNAs (dsRNAs) targeted against essential genes, strong gene silencing and mortality can be induced. To exert their function, dsRNA molecules must pass through the insect’s gut and enter epithelial cells and/or the hemolymph. Gut bacteria are known to play multifarious roles in food digestion and nutrition, and confer protection against pathogens and parasites. Whether there is a cross talk between gut bacteria and ingested dsRNAs and whether the microbiome affects RNAi efficiency are unknown.

Results

Here, using a leaf beetle gut microbiota system, we investigated whether gut bacteria interact with dsRNA molecules and how the gut microbiota affects RNAi responses in insects. We first showed that the leaf beetle Plagiodera versicolora (Coleoptera) is highly susceptible to RNAi. We then demonstrated that ingestion of dsRNAs by non-axenic P. versicolora larvae results in (i) significantly accelerated mortality compared with axenic larvae, and (ii) overgrowth and dysbiosis of the gut microbiota. The latter may be caused by bacterial utilization of dsRNA degradation products. Furthermore, we found that Pseudomonas putida, a gut bacterium of P. versicolora, acts as major accelerator of the death of P. versicolora larvae by transitioning from commensal to pathogenic lifestyle.

Conclusions

The present study illuminates the complex interplay between lethal dsRNA, the insect host, and its gut microbiota. The ingestion of dsRNA by the leaf beetle caused a dysbiosis of gut bacterial community, and the dsRNA degradation products by host insect preferentially promoted the growth of an entomopathogenic bacterium, which accelerated dsRNA lethality to the insect. Our findings reveal a synergistic role of the gut microbiota in dsRNA-induced mortality of pest insects, and provide new insights in the mechanisms of RNAi-based pest control.
Production forecast and estimation of the recovery factor of the Los Humeros geothermal field, Mexico
Authors: González-García Héctor , Francke Henning , Sass Ingo , Huenges Ernst
Published: May 2021

Production data from the Los Humeros geothermal field in Mexico are used to develop a forecast method for operation of the field in the future. This method supports understanding the limitations of sustainably exploiting a geothermal reservoir. Using such forecasts, fluid extraction could be scheduled in order to fulfill the steam demand of the installed capacity. Moreover, the forecast of the extraction can diminish the commercial risk involved and therefore clear the way for new investments. Herein, we determined the total extracted heat from the Los Humeros geothermal system, with the aim to forecast the next phase of fluid extraction. We took the information from 29 producing wells to analyze their historic geothermal fluid production. From their statistical distribution of data, we estimated the amount of extracted fluids for a future phase. The size of the heat reserve previous to exploitation was calculated from the forecasted and the extracted heat. Thus, the recovery factor of the system was calculated as the ratio of the accumulated production of heat and the initial heat in place. The general recovery factor for 60 years of production was calculated as 37–44%. Due to the heterogeneity of the system, this study conducted individual assessments. The forecasted heat extraction for the next 30 years of production, amounts to 580 PJ assuming a constant extraction rate between 6 and 56 ton·[h]−1 depending on the particular well. The results of this study potentially complement the existing models of the geothermal exploitation and offer an estimation of the future production of the Los Humeros, which could be a good basis for decision-making and management of the site.
Parkin and its molecular associations in gliomas – a systematic review
Authors: de Castro Eduardo Morais , Barbosa Leonardo Vinícius , Ferreira João Vitor Alves , de Andrade Diancarlos Pereira , Mello Rosiane Guetter , Torres Luiz Fernando Bleggi , de Noronha Lucia , Machado-Souza Cleber
Published: May 2021

Parkin, a protein encoded by PRKN, discovered in the context of Parkinson’s disease, controls proteasomal degradation by protein ubiquitination and acts on cell cycle control and mitochondrial homeostasis, among other cellular processes. Parkin has been also implicated in several carcinomas, melanoma and leukemia. In the neoplastic setting, reduced parkin level usually indicates poorer prognosis. Some authors have described the associations between parkin and gliomas. Gliomas are a heterogeneous group of tumors that arise in the central nervous system, astrocytomas being the most common. The aim of this systematic review is to evaluate how parkin behaves in gliomas and the molecular pathways associated in this interaction. A search was conducted in PubMed, EBSCO and Scopus and 8 published articles were identified as eligible studies. The studies were categorized in three groups, according to their main emphasis: PRKN mutation patterns detected in gliomas, parkin effects on tumor growth and survival rates, and molecular interactions between parkin and other proteins. The studies showed higher PRKN mutation rates and lower parkin expression in high grade gliomas. Patients with higher parkin expression had better overall survival. Besides, different molecular pathways associated with parkin were described, some of them regarded as potential therapeutic targets.
Mid-term clinical and radiographic outcomes of porous-coated metaphyseal sleeves used in revision total knee arthroplasty
Authors: Gurel Ron , Morgan Samuel , Elbaz Etay , Ashlenazi Itay , Snir Nimrod , Kadar Assaf , Gold Aviram , Warschawski Yaniv
Published: May 2021

Background

The management of bone defects remains one of the major challenges surgeons are faced with in revision total knee arthroplasty (RTKA). Large and uncontained bone defects are traditionally managed with metaphyseal sleeves that facilitate osseointegration and have reported construct stability. While many studies have presented excellent short-term outcomes using metaphyseal sleeves, less is known on their performance in the longer term. The purpose of this study was to present our mid-term results of the metaphyseal sleeves used in patients undergoing RTKA.

Materials and methods

Between January 2007 and January 2015, 30 patients underwent RTKA with the use of a CCKMB prosthesis combined with an osteointegrative sleeve. The main indications for RTKA were instability in 40% of the cases (n = 12), aseptic loosening in 30% (n = 9), infection in 26.7% (n = 8), and “other” in 3.3% (n = 1). The minimal follow-up time was 5 years and the mean follow-up time was 82.4 months (SD = 22.6). Clinical outcomes were assessed by Knee Society scores (KSS), range of motion and rate of re-operation.

Results

The mean Knee Society score increased significantly from 72.1 preoperatively to 90.0 postoperatively (p < 0.001). The cumulative incidence of re-operation in our study was 13.3% (n = 4). Our study reported no cases of aseptic loosening or mobile-bearing spin-out. Knee flexion to 90° and more was impossible in seven cases (23.3%) preoperatively and in one case (3.3%) postoperatively.

Conclusion

Porous-coated metaphyseal sleeves demonstrated excellent rates of survivorship and radiographic ingrowth in the mid-term setting. However, further studies are required to assess their outcomes in the long-term.
Can ultrasound suffice for triaging patients requiring surgical correction of rotator cuff tears—a comparative evaluation of ultrasound and magnetic resonance imaging
Authors: Agarwal Aniket , Vani Kavita , Batta Anurag , Verma Kavita , Chumber Shishir
Published: May 2021

Background

Objectives: To comparatively evaluate the role of ultrasound and MRI in rotator cuff and biceps tendon pathologies and to establish ultrasound as a consistently reproducible, quick and accurate primary investigation modality sufficient to triage patients requiring surgical correction of full thickness rotator cuff tears. Methods: Fifty patients, clinically suspected to have rotator cuff and/or biceps tendon pathologies, with no contraindications to MRI, were evaluated by US and MRI, in a prospective cross-sectional observational study. US was done with high-frequency linear probe, and MRI was done on a 1.5-T scanner using T1 oblique sagittal, proton density (PD)/T2 fat-suppressed (FS) oblique sagittal, T1 axial, PD/T2 FS axial, T1 oblique coronal, T2 oblique coronal and PD FS oblique coronal sequences. Statistical testing was conducted with the statistical package for the social science system version SPSS 17.0. The sensitivity, specificity, PPV, NPV and accuracy were also calculated to analyze the diagnostic accuracy of US findings correlating with MRI findings. A p value less than 0.05 was taken to indicate a significant difference.

Results

Mean age was 45 years; 74% patients were males; 77% females and 60% males had tears. Majority of patients with rotator cuff tears were in the sixth decade of life. The frequency of tears was higher among older patients. Fourteen percent of patients had full thickness tears while 64% had partial thickness tears. US was comparable to MRI for detection of full thickness tears with overall sensitivity, specificity, PPV and accuracy of 93.8%, 100%, 100% and 98.2%, respectively (p value < 0.001). For partial thickness tears, US had overall sensitivity, specificity, PPV and accuracy of 75.6%, 82.6%, 89.5% and 78%, respectively (p value < 0.001), as compared to MRI. Subacromial-subdeltoid bursal effusion and long head of biceps tendon sheath effusion were common associated, though, non-specific findings.

Conclusion

Ultrasound findings in our study were found to be in significant correlation with findings on MRI in detection of rotator cuff tears. US was equivalent to MRI in detection of full thickness tears and fairly accurate for partial thickness tears. Therefore, US should be considered as the first line of investigation for rotator cuff pathologies.
The pattern of cardiovascular manifestations in Egyptian Behçet’s patients and its relation to disease activity
Authors: Morshedy Nashwa Aly , Mohammed Dalia Fayez , Badr Fatma Mohammed , Teama Mohammed Abd El monem
Published: May 2021

Background

Behçet’s disease (BD) is also referred to as vascular BD when it frequently involves the heart and vessels. This study aimed to describe the cardiovascular manifestations in patients with BD and its correlation to disease activity. We conducted a cross-sectional study on 40 patients diagnosed with BD according to the International Criteria for Behçet’s Disease 2014. All the patients were subjected to detailed history taking, full clinical examination, lab investigations, resting electrocardiogram, trans-thoracic echocardiography, and carotid artery duplex for measuring intimal thickness, peripheral arterial and venous duplex, computed tomography pulmonary angiography, and full ophthalmological examination. Regarding the activity of the disease, it was assessed according to the score of Behçet’s Disease Current Activity Form (BDCAF).

Results

The most common cardiac manifestation was valvular lesion (67.5%) where the most frequently affected valve was the tricuspid valve (27.5%). Although 25% of patients had left ventricular diastolic dysfunction, only 5% had intracardiac masses. Approximately 52.5% of patients had vascular lesion (deep venous thrombosis 45%, arterial involvement 7.5% [as pulmonary artery thrombosis 5% and aneurysm 2.5%]). Increase in intima media thickness (IMT) was observed in 7.5% of patients, while 60% had abnormal lipid profiles. Hypercholesterolemia was the most common lipid abnormality (50%). BDCAF score range was 4–12, which was significantly correlated to multiple cardiovascular parameters as a mitral, tricuspid valve, and vascular venous involvement (p < 0.05), while not significantly correlated to lipid profile (p > 0.05).

Conclusion

Cardiovascular complications are frequent among patients with BD, even those who are asymptomatic; therefore, these complications must be screened for early detection and proper management.
Gender differences in the comorbidity of neurological and psychological disorders in a large clinical sample of children
Authors: Brandt Valerie , Napoleone Elisa , Patalay Praveetha
Published: May 2021

This study aimed to establish rates and gender patterns of 25 comorbidities in 1912 children (72% male) with a neurological disorder and a comparison group (n = 40 718, 45% male) from a large clinical records data-set in child mental health services in the UK with clinician-recorded data on neurological and psychological conditions. Obsessive–compulsive disorder, oppositional defiant/conduct disorders, autism spectrum disorders and intellectual disabilities (also known in UK health services as learning disabilities) occurred significantly more often in both boys and girls with neurological disorders than in the comparison group. Girls with neurological disorders showed a ‘male-typic’ comorbidity profile.
Ixazomib, Daratumumab, and Low-Dose Dexamethasone in Frail Patients With Newly Diagnosed Multiple Myeloma: The Hovon 143 Study
Authors: Stege Claudia A. M. , Nasserinejad Kazem , van der Spek Ellen , Bilgin Yavuz M. , Kentos Alain , Sohne Maaike , van Kampen Roel J. W. , Ludwig Inge , Thielen Noortje , Durdu-Rayman Nazik , de Graauw Nicole C. H. P. , van de Donk Niels W. C. J. , de Waal Esther G. M. , Vekemans Marie-Christiane , Timmers Gert Jan , van der Klift Marjolein , Soechit Savita , Geerts Paul A. F. , Silbermann Matthijs H. , Oosterveld Margriet , Nijhof Inger S. , Sonneveld Pieter , Klein Saskia K. , Levin Mark-David , Zweegman Sonja
Published: May 2021

PURPOSE

Frail patients with newly diagnosed multiple myeloma have an inferior outcome, mainly because of a high discontinuation rate due to toxicity. We designed a phase II trial specifically for frail patients, evaluating the efficacy and tolerability of ixazomib-daratumumab-low-dose-dexamethasone (Ixa-Dara-dex).

METHODS

Sixty-five patients, who were frail according to the International Myeloma Working Group frailty index, were treated with nine induction cycles Ixa-Dara-dex followed by maintenance with Ixa-Dara for a maximum of 2 years.

RESULTS

The overall response rate on induction therapy was 78%. After a median follow-up of 22.9 months, median progression-free survival (PFS) was 13.8 months and 12-month overall survival (OS) was 78%. Median PFS and 12-month OS were 21.6 months and 92% in patients who were frail based on age > 80 years alone, versus 13.8 months and 78%, and 10.1 months and 70% in patients who were frail based on additional frailty parameters either ≤ 80 or > 80 years of age, respectively. In 51% of patients, induction therapy had to be discontinued prematurely, of which 6% because of noncompliance to study treatment, 9% because of toxicity, and 9% because of death (8% within 2 months, of which 80% because of toxicity). Quality of life improved during induction treatment, being clinically meaningful already after three induction cycles.

CONCLUSION

Ixa-Dara-dex lead to a high response rate and improved quality of life. However, treatment discontinuation because of toxicity and early mortality, negatively influencing PFS and OS, remains a concern in frail patients. The outcome was heterogeneous across frail subpopulations. This should be taken into account in the design and interpretation of future studies in frail patients, to pave the way for more precise treatment guidance.
Performance of molecular methods for the detection of Salmonella in human stool specimens
Authors: Chirambo Angeziwa Chunga , Nyirenda Tonney S. , Jambo Ndaru , Msefula Chisomo , Kamng'ona Arox , Molina Sandra , Mandala Wilson L. , Heyderman Robert S. , Iturizza-Gomara Miren , Henrion Marc Y.R. , Gordon Melita A.
Published: May 2021

Background: The relationship between asymptomatic Salmonella exposure within the gastrointestinal tract and Salmonella bacteraemia is poorly understood, in part due to the low sensitivity of stool culture and the lack of validated molecular diagnostic tests for the detection of Salmonella in the stool. The study aimed to determine a reliable molecular diagnostic test for Salmonella in stool specimens.

Methods: We optimised an in-house monoplex real-time polymerase chain reaction (PCR) for the detection of Salmonella ttr and InvA genes in stool by including a selenite broth pre-culture step for Salmonella before DNA extraction and validated their specificity against other local common pathogens. Then we assessed their performance against a well-validated multiplex PCR targeting the same ttr and InvA genes and against stool culture using clinical stool specimens collected from a cohort of 50 asymptomatic healthy Malawian children that were sampled at 1-month intervals over 12 months. We employed a latent Markov model to estimate the specificities and sensitivities of PCR methods.

Results: Ttr and InvA primers were both able to detect all the different Salmonella serovars tested and had superior limits of detection when DNA was extracted after selenite pre-culture. Ttr sensitivity and specificity for monoplex-PCR were (99.53%, 95.46%) and for multiplex-PCR (90.30%, 99.30%) respectively. InvA specificity and specificity for using monoplex-PCR was (95.06%, 90.31%) and multiplex-PCRs (89.41%, 98.00%) respectively. Sensitivity and specificity for standard stool culture were 62.88% and 99.99%, respectively. Culture showed the highest PPV (99.73%), and monoplex-ttr had the highest NPV (99.67%).

Conclusion: Test methods demonstrated high concordance, although stool culture and monoplexed ttr primers had superior specificity and sensitivity, respectively. The use of selenite pre-enrichment step increased Salmonella detection rate. Taken together, molecular detection methods used here could be used to reveal the true extent of both asymptomatic and symptomatic Salmonella exposure events.
Increased expression of Polδ does not alter the canonical replication program in vivo
Authors: Zach Róbert , Carr Antony M.
Published: May 2021

Background: In vitro experiments utilising the reconstituted Saccharomyces cerevisiae eukaryotic replisome indicated that the efficiency of the leading strand replication is impaired by a moderate increase in Polδ concentration. It was hypothesised that the slower rate of the leading strand synthesis characteristic for reactions containing two-fold and four-fold increased concentration of Polδ represented a consequence of a relatively rare event, during which Polδ stochastically outcompeted Polε and, in an inefficient manner, temporarily facilitated extension of the leading strand. Inspired by this observation, we aimed to determine whether similarly increased Polδ levels influence replication dynamics in vivo using the fission yeast Schizosaccharomyces pombe as a model system.

Methods: To generate S. pombe strains over-expressing Polδ, we utilised Cre-Lox mediated cassette exchange and integrated one or three extra genomic copies of all four Polδ genes. To estimate expression of respective Polδ genes in Polδ-overexpressing mutants, we measured relative transcript levels of cdc1+, cdc6+ (or cdc6L591G), cdc27+ and cdm1+ by reverse transcription followed by quantitative PCR (RT-qPCR). To assess the impact of Polδ over-expression on cell physiology and replication dynamics, we used standard cell biology techniques and polymerase usage sequencing.

Results: We provide an evidence that two-fold and four-fold over-production of Polδ does not significantly alter growth rate, cellular morphology and S-phase duration. Polymerase usage sequencing analysis further indicates that increased Polδ expression does not change activities of Polδ, Polε and Polα at replication initiation sites and across replication termination zones. Additionally, we show that mutants over-expressing Polδ preserve WT-like distribution of replication origin efficiencies.

Conclusions: Our experiments do not disprove the existence of opportunistic polymerase switches; however, the data indicate that, if stochastic replacement of Polε for Polδ does occur in vivo, it represents a rare phenomenon that does not significantly influence canonical replication program.
Formation of Communicative Competence of Personnel
Authors: Omel'chenko N. , Skripnichenko L.
Published: May 2021

The ongoing processes in society related to globalization, improvement of information and communication flows contribute to the expansion of contacts between people, developing a corporate culture, social and communicative competence of staff. Communicative competence is a qualitative characteristic of the individual, responsible for realizing the need for social recognition, self-actualization, and therefore contributing to the development of successful socialization. The concept can include a set of knowledge and skills that ensure the effective functioning of the communication process.

This concept is a component of a competent approach in working with the organization's personnel.

Today, it is impossible to imagine a specialist without communicative knowledge, skills and skills. The communicative competence of personnel gets an important role in modern conditions of development of economy where major factors is knowledge, abilities, skills of personnel.

It is important to note that the formed communication competence is especially necessary for managers. It is the main tool for managing tasks.

The results of the personnel's work can be considered through the results of the production, economic and other activities of the organization or subdivisions, as well as through the socio-economic working conditions of employees subordinate to it. The formed communication competence will help to achieve the goals set for the organization, increase efficiency and ensure the growth of the company, which directly affects the stability of personnel and customer loyalty. In order to analyze the peculiarities of the formation of comunicative competence of the personnel of the organization, the authors attempted to conduct this study.
Features of Personnel Management at the Enterprises of the Hotel Industry
Authors: Shostak Marina , Yakovleva Mariya
Published: May 2021

The specific features of personnel management at hospitality industry’ enterprises have been identified and formulated in the article. Since personnel is a key multifunctional resource in the hotel business, the research analyses in close-up how the specificity of HR-management is manifested in the personnel management’s functions in hotels. The identified specific features define the characteristics of business processes in the hotel industry and reveal the mechanisms for improving the personnel management system. The factors having a direct impact on the characteristics of personnel management, the labor market in the hotel industry and the cause-and-effect relationships of influence will receive attention in the authors’ further research. HR managers, specialists interacting with human resources, undergraduate and postgraduate students specializing in Management will benefit from studying this material, as it will deepen their professional knowledge and competencies in the field of understanding the features of personnel and human resources management at the hospitality industry establishments.
Problems of Improving Organizational Structures Management of Construction Companies
Authors: Panin V. , Belikova D.
Published: May 2021

In this article, special attention is paid to the issues of improving the organizational structures of management of companies in the construction industry. The criteria for changes in the management structure of the company are being specified; tasks that pose the transformation and optimization of the management structure to business entities. The main reasons for the search for new organizational structures of management in the organizations of the investment and construction sphere are considered; the main reasons that prevent the introduction of methods of structural adjustment. The main problems of the formation and improvement of organizational structures of management in the investment and construction sphere at different levels of the organization are raised. Attention is focused on the main tasks of modernizing the organizational structure of company management.