bluuebunny/crossref_metadata_2025_split huggingface dataset:
The novel membrane protein Hoka regulates septate junction organization and stem cell homeostasis in the Drosophila gut
Authors: Izumi Yasushi , Furuse Kyoko , Furuse Mikio 
Published: February 2021

ABSTRACT
Smooth septate junctions (sSJs) regulate the paracellular transport in the intestinal tract in arthropods. In Drosophila, the organization and physiological function of sSJs are regulated by at least three sSJ-specific membrane proteins: Ssk, Mesh and Tsp2A. Here, we report a novel sSJ membrane protein, Hoka, which has a single membrane-spanning segment with a short extracellular region, and a cytoplasmic region with Tyr-Thr-Pro-Ala motifs. The larval midgut in hoka mutants shows a defect in sSJ structure. Hoka forms a complex with Ssk, Mesh and Tsp2A, and is required for the correct localization of these proteins to sSJs. Knockdown of hoka in the adult midgut leads to intestinal barrier dysfunction and stem cell overproliferation. In hoka-knockdown midguts, aPKC is upregulated in the cytoplasm and the apical membrane of epithelial cells. The depletion of aPKC and yki in hoka-knockdown midguts results in reduced stem cell overproliferation. These findings indicate that Hoka cooperates with the sSJ proteins Ssk, Mesh and Tsp2A to organize sSJs, and is required for maintaining intestinal stem cell homeostasis through the regulation of aPKC and Yki activities in the Drosophila midgut.
Optimising retention success: a research team’s experience of following-up participants recruited to a pilot trial through community pharmacies in England
Authors: Watson Michelle , van Dongen Anne , Hewitt Catherine , Mandefield Laura , Stewart Duncan , Watson Judith , McCambridge Jim 
Published: February 2021

Background: The CHAMP-1 (Community pharmacy: Highlighting Alcohol use in Medication aPpointments) pilot trial aimed to explore an intervention discussing alcohol during medication consultations with community pharmacists. It presented various challenges regarding patient retention, as participants were recruited by their pharmacist and followed-up remotely by a trained researcher, who they had not met, two months later. We discuss our actions and experiences of completing follow-up activities. Methods: Community pharmacists recruited patients aged 18 and over, attending a Medicine Use Review (MUR) or New Medicine Service (NMS) consultation, and drinking alcohol at least twice per week. Pharmacies were randomised to conduct their consultations as usual (control), or to incorporate the Medicines and Alcohol Consultation (MAC) intervention. All participants were followed-up by a researcher after two months to complete data collection via telephone or post. We employed standard follow-up strategies, including a plan to text participants with a reminder in advance of their follow-up. Results: Forty-seven of 51 participants (92%) completed the two month follow-up. Thirty-eight (81%) responses were provided by telephone and nine (19%) by post. Of the 38 follow-up calls completed by telephone, 17 (45%) participants were reached at first attempt; 16 (42%) at second attempt; and five (13%) at the third attempt. We observed a high percentage of data completion across telephone and postal collection methods. Participants were willing to discuss potentially sensitive issues, such as alcohol consumption, anxiety, and depression, with a researcher who was external to the pharmacy team. Conclusions: The results suggest that patients recruited to a trial by community pharmacists are willing to take part in data collection activities, and remote follow-up can be successfully conducted by researchers. The techniques employed to encourage high levels of retention should be investigated further in a larger study, alongside consideration of optimal strategies to collect data within community pharmacies.
Associated predictor covariates of cervical cancer and impact on survival at Khartoum oncology hospital, Sudan
Authors: Elgoraish Amanda , Alnory Ahmed 
Published: February 2021

Background: Cervical cancer can be invasive and advanced at diagnosis causing devastating suffering and premature death. Cancer stage at presentation is related to survival evaluation and several factors determine stage. The aim of the study was to examine predictors covariates associated with cervical cancer stage and its impact on patient prognosis and survival. Methods: This retrospective cross-sectional study was carried out at Khartoum oncology hospital, Sudan. Participants were 239 cervical cancer patients diagnosed and treated between 2011-2015. Patients’ pathological and socio-demographic data were extracted from their medical files and survival times calculated from follow-up. Chi-square, Kaplan-Meier, Log-rank test and Cox regression model were used to examine relationships between demographic and clinical variables and survival outcome. Results: The mean age of the participants was 56.91 years and the majority were ≥45 years. Cancer survival analysis showed that stage at diagnosis had limited association with socio-demographic factors, with the exception of where patients residing. Multivariate regression using the Cox proportional hazard model confirmed strongly that stage (p=0.035, chemotherapy (p=0.000) and radiotherapy (p=0.001) were the most likely predictor covariates of patient prognosis and survival time. Conclusions: The results of this study suggest cancer stage at diagnosis and certain treatments are the most important factors impacting prognosis and survival of patients with cervical cancer. Early detection and vaccination of women against HPV infection provide enormous opportunities for early diagnosis, more effective treatment and better chances of survival.
Study protocol for the COvid-19 Toolbox for All IslaNd (CONTAIN) project: A cross-border analysis in Ireland to disentangle psychological, behavioural, media and governmental responses to COVID-19
Authors: Darker Catherine D. , O'Connell Nicola , Dempster Martin , Graham Christopher D. , O'Connor Cliodhna , Zgaga Lina , Nolan Ann , Tobin Katy , Brennan Niamh , Nicolson Gail , Burke Emma , Mather Luke , Crowley Philip , Scally Gabriel , Barry Joseph 
Published: February 2021

COVID-19 represents a serious challenge to governments and healthcare systems. In addition to testing/contact tracing, behavioural and social responses such as handwashing and social distancing or cocooning are effective tools for mitigating the spread of the disease. Psychological (e.g., risk perceptions, self-efficacy) and contextual factors (government, public health messaging, etc.) are likely to drive these behaviours. Collated real-time information of these indicators strengthens local, national and international public health advice and messaging. Further, understanding how well public health and government messages and measures are understood, communicated via (social) media and adhered to is vital. There are two governments and public health jurisdictions on the island of Ireland, the Republic of Ireland (ROI) and Northern Ireland (NI). This represents an opportunity to explore implications of differing measures and messaging across these two jurisdictions as they relate to COVID-19 on two similar populations. The expert research team are drawn from a range of disciplines in the two countries. This project has four nested studies: Assessment of key behavioural, social and psychological factors through a large, prospective representative telephone survey of individuals aged over-18 on a weekly basis over eight weeks (n=3072); and conduct qualitative focus groups over the same period.Interrogation of social media messaging and formal media responses in both jurisdictions to investigate the spread of (mis)information.Modelling data from Studies 1 and 2, plotting the psychosocial/behavioural and media messaging information with international, ROI and NI incidence and mortality data. Conducting an assessment of health policy transfer in an attempt to incorporate the most significant public health and political insights from each jurisdiction. The CONTAIN project will develop an evidence-based toolbox for targeting public health messaging and political leadership and will be created for use for the anticipated second wave of COVID-19, and subsequently for future epidemics/pandemics.
A Tríade Sombria da Personalidade: Afetos e Lócus de Controle
Authors: Bonfá-Araujo Bruno , Costa Ariela Raissa Lima , Cremasco Gabriela da Silva , Sette Catarina Possenti , Jesuíno Ana Deyvis Santos Araújo 
Published: February 2021

A tríade sombria da personalidade —narcisismo, maquiavelismo e psicopatia— retrata características antagonistas, insensíveis e socialmente aversivas. É sabido que diversos fatores são afetados por traços de personalidade, tanto saudáveis quanto psicopatológicos. Este estudo buscou compreender a capacidade explicativa da tríade sombria nos afetos positivos e negativos e no lócus de controle. Para tanto foram realizados dois estudos. Compuseram o primeiro deles 154 participantes, com média de idade de 27,14 anos (DP = 9,28) que responderam ao Dirty Dozen e a Escala de Afetos Positivos e Negativos. O segundo estudo foi composto por 660 participantes, com média de idade 22,83 anos (DP = 7,21) que foram avaliados pelo Short Dark Triad e a Escala Multidimensional de Lócus de Controle. Os resultados indicaram que a tríade sombria explica positivamente os afetos negativos, enquanto maquiavelismo explica negativamente lócus de controle externo e narcisismo e psicopatia explicam o lócus de controle interno —de maneira negativa e positiva, respectivamente. Tais achados são possíveis explicações para os desfechos aversivos em indivíduos com altos escores na tríade sombria, de modo que estes vivenciam mais desprazer e raiva, como também se eximem de suas responsabilidades emocionais e se satisfazem ao notarem que causam danos em terceiros.
Impairment of microvascular blood flow in patients with type 2 diabetes and cardiovascular autonomic neuropathy
Authors: Zelenina T. A. , Salukhov V. V. , Zemlianoi A. B. , Zheleznjak S. G. , Klitsenko O. A. 
Published: February 2021

BACKGROUND: Diabetic autonomic neuropathy is the reason for early morbidity and mortality on diabetic patients. The pathology not only cardiac innervation but microvascular is presented.AIMS: We estimated the parameters of skin microvascular blood flow in accordance with cardiovascular autonomic neuropathy (CAN) staging in diabetic patients. We also assessed other risk factors of CAN in patients with diabetes.MATERIALS AND METHODS: We included 76 patients with type 2 diabetes in the study (24 patients with resent-onset diabetes and/or diabetes without microvascular complications, 26 with diabetic sensorimotor neuropathy (SMN) and 26 with SMN and previous history of diabetic foot amputation). The SMN was diagnosed on the basis of patients complaints, anamnesis and data of clinical neurological examinations. CAN was detected using several cardiovascular autonomic reflex tests (CART) as a gold standard of diagnosis: the tilt-table test, a deepbreathing and Valsalva Maneuver, handgrip test, cold-stress vasoconstriction. According to the Toronto Diabetic Neuropathy Expert Group Recommendation all patients was separated on the groups: CAN 0 (all CARTs were normal), CAN 1 (possible/early CAN — one abnormal CART was presented), CAN 2 (definite/confirmed CAN –at least two abnormal CARTs were found), CAN 3 (severe/advanced CAN — in the cases of orthostatic hypotension in addition to CARTs abnormalities). Microvascular blood flow of skin at the nail roller of fingers skin was valuated at rest as well as in functional cold test by the method of High-frequency Ultrasonic Dopplerography using the “Minimax Doppler K” device (LLC JV “Minimax”, St. Petersburg, Russia).RESULTS: CAN 1 was found in 8% diabetic patients without microvascular complications, 42 and 21% patients with SMN and diabetic foot amputations respectively. CAN 2 was diagnosed in 27% patients with SMN and 58% patients history of diabetic foot amputations. CAN 3 in 8% and 19% cases in patients with SMN and history of diabetic foot amputations respectively. The parameters of microvascular blood flow at rest were significantly decreased in patients with confirmed/severe CAN in comparison with early staging of CAN and patients without CAN (Vm=2.5±0.66 sm/sec vs. 4.4±0.54 sm/sec and 5.1±1.01 sm/sec respectively; p=0.0033). The abnormal result of cold test was detected in 94% patients with confirmed/ severe CAN and 26% patients with CAN 1.CONCLUSIONS: This investigation has demonstrated in a cohort with type 2 diabetes patients with/without SMN and with/ without history of previously foot amputations that decrease the Vm (the variable of microvascular blood flow assessed by High-frequency Ultrasonic Dopplerography) lower than 2.4 sm/sec is associated with 6.4 times increased likelihood of confirmed/severe CAN as well as positive cold test result. That the patients with positive cold test results were 28.6 times more likely have confirmed/severe CAN.
Structural and functional indicators of the heart of patients with ischemic heart disease and type 2 diabetes mellitus. Rhythmoinotropic response isolated myocardium at different levels of glycated hemoglobin
Authors: Kondratieva D. S. , Afanasiev S. A. , Budnikova O. V. , Vorozhtsova I. N. , Akhmedov S. D. , Kozlov B. N. 
Published: February 2021

BACKGROUND: Adequate glycemic control can significantly reduce the risk of developing cardiovascular events. However, until now, glycaemic targets in aged patients remain a subject of discussion, especially in the conditions of the combined development of Type 2 Diabetes Mellitus (T2DM) and ischemic heart disease (IHD).AIMS: To examine the structural and functional heart parameters in patients with IHD associated with T2DM and the rhythmoinotropic responses of their isolated myocardium depending on glycated hemoglobin level.MATERIALS AND METHODS: The study included 44 patients with a diagnosis of "chronic IHD associated with T2DM", of which 2 groups were formed. Patients with glycated hemoglobin level (HbA1c) <8% were included in the 1st group, and patients with HbA1c ≥8% were included in the 2nd group. The structural and functional heart parameters obtained with ultrasonography, and the rhythmoinotropic responses of myocardium in patients ex vivo were analyzed using the right atrial appendage fragments obtained during elective coronary artery bypass graft. The inotropic response of muscle strips at a basic stimulation frequency of 0,5 Hz to testing influences was assessed. An extrasystolic test and post-rest test were performed.RESULTS: It was found that extrasystolic contractions of isolated myocardial strips in patients of the 2nd group appeared at shorter extrasystolic intervals, which indicates a greater excitability of the myocardium in patients of this group. Postextrasystolic muscle contractions in patients of the 2nd group had significant potentiation. The amplitude of the muscle strips contractions in patients of both groups was potentiative after short rest periods. However, with an increase in the rest duration, potentiation of contractions was observed only in the group with a higher HbA1c level. According to the ultrasonography data, it was found that the values of the endsystolic and diastolic volumes, the interventricular septum thickness and the left ventricular (LV) myocardium mass were significantly lower in the patients of the 1st group compared with the corresponding indicators in the patients of the 2nd group. The early LV filling velocity (peak E) was significantly lower in the patients of the 1st group, which indicates a slower LV relaxation. At the same time, the rapid LV filling velocity did not have a significant intergroup difference, but this indicator exceeded the reference values in both groups.CONCLUSIONS: With a moderately increased glycemic level (9,2 [8,0; 10,3]%), the structural and functional heart parameters are preserved both at the level of the isolated myocardial tissue and at the level of the whole heart.
Results of a clinical trial of the efficacy and safety of vildagliptin and metformin fixed combination in real clinical practice in Russia (MASTER study)
Authors: Demidov N. A. , Antsiferov M. B. , Zilov A. V. 
Published: February 2021

BACKGRAUND: The widespread prevalence of type 2 diabetes mellitus (T2DM), high mortality and disability of such patients are the reason for the constant active search for effective approaches to hypoglycemic therapy. Recent years have been marked by a change in the strategy for treatment initiation of T2DM. In clinical studies, evidence has been obtained about the benefits of prescribing combination therapy from the time of diagnosis. It seems important to study this treatment option also in real clinical practice.AIMS: To evaluate the effectiveness and safety of the initiation with Galvus Met® as compared with any other combination therapy approaches used in everyday clinical practice.MATERIALS AND METHODS: multicenter prospective observational study in 15 regions of Russia lasting 6 months. Patients were included in the study after the endocrinologist made a decision on the appointment of therapy. Of the men and women over 18 years of age with first diagnosed or previously untreated type 2 diabetes and a level of glycated hemoglobin >7.5%, two groups were formed. The first group included patients who received vildagliptin + metformin (Galvus Met®) in a fixed dose of 50/1000 mg, n=729, the second — another double combination (with the exception of insulin and GLP-1), n=669. The primary endpoint was defined as the proportion of patients (%) who achieved the level of HbA1c <7.0% without proven hypoglycemia at the end of the observation. The NHPQ questionnaire was used to assess the frequency of hypoglycemia.RESULTS: 1385 patients completed the study. For the other combination therapy group, metformin and sulfonylurea derivatives were most often selected (66.5%). In the Galvus Met® group, 68.7% of patients achieved an HbA1c level of <7.0% without proven hypoglycemia, which is significantly better compared to the group of other combinations (40.7%, p <0.001). Galvus Met® therapy contributed to a significantly greater decrease in HbA1c levels by the end of the study compared to other combinations (delta HbA1c -1.6 ± 0.8% versus -1.4 ± 0.9%, p <0.001). In the same group, the average level of HbA1c reached 6.7 ± 0.6% by the end of the study versus 7.1 ± 0.8% in the comparison group, p <0.001. In the Galvus Met® group, body weight decreased by 3.2 ± 3.9 kg, and in the comparison group by 1.3 ± 4.8 kg, p <0.001. The frequency of hypoglycemia episodes in the Galvus Met® group by the end of the study was significantly lower than in the comparison group: 0.8 ± 0.7 episodes per person, versus 1.4 ± 0.8, p = 0.037. In the Galvus Met® group, there were significantly fewer adverse events (4.9% versus 17.7%, p <0.001).CONCLUSIONS: In real clinical practice, Galvus Met® starting therapy has shown better efficacy and safety in terms of achieving glycemic control, HbA1c dynamics, effects on body weight, the frequency of hypoglycemic conditions compared with other combined oral hypoglycemic therapy.
On the centenary of the insulin discovery
Authors: Dedov I. I. , Shestakova M. V. 
Published: February 2021

The discovery of insulin and the beginning of its use in 1921–1922 made a revolution in endocrinology and in medicine in general. This significant event gave millions of patients with diabetes not only the opportunity to live, but also the hope that their life with this disease would be full.The article examines the history of insulin discovery, as well as the evolution of several generations of insulin preparations and the advantages of each of the generations that have radically changed not only life expectancy, but also its quality.The first generation — insulins of animal origin and the solution of the first tasks of their sufficient production and purification. The next generation is human insulins, the purification of which was also a problem. The third generation is insulin analogues, the action of which became closer to the action profile of natural insulin. And the last generation — insulin analogues, most closely mimicking the action of endogenous insulin.Along with the development of insulin preparations, the article traces the evolution of the devices of its administration.
The prospects for the creation of the National Center for Personalized Medicine of Endocrine Diseases
Authors: Dedov I. I. , Mokrysheva N. G. , Shestakova M. V. , Volchkov P. Y. , Mayorov A. Y. , Rebrova O. Yu. , Barysheva V. O. , Krupinova Ju. A. , Troshina E. A. , Dzeranova L. K. , Melnichenko G. A. 
Published: February 2021

The National Medical Research Center for Endocrinology (NMRCE) received the right to implement the development program of the World-class Research Centre “The National Center for personalized medicine of endocrine diseases” (NMCPMED). The objective of the NMCPMED will be not only the creation of a system of personalized treatment, but also the training of new specialists for medicine. Fundamental researches, carried out on the basis of the already existing institutes and laboratories of the NMRCE will be expanded by creating new laboratories of the NCPMED created de novo in accordance with the approved project. This article introduces the reader to the most important laboratories that would be created in NCPMED. These are laboratories of general, molecular and population genetics, bioinformatics, pharmacogenomics, microbiota, genome editing, mathematical and digital technologies, non-invasive technologies for the diagnosis of endocrinopathies, cellular technologies, artificial intelligence and a fundamentally new laboratory of metabolic visualization and radioteranostics. The authors hope that readers of one of the main journals for endocrinologists in our country will actively participate in the implementation of NMRCE, as both young and experienced talented researchers will have a chance to be a part of the Centre. To realize the ambitious implementation plans for the achievements of the Centre, it is necessary to radically change the worldview of the doctors in our country, to train them in a new way, and to expand the structure of the Center’s team by increasing the number of specialists in medical genetics, transcriptomics, biostatistics and bioinformatics, working at the intersection of experimental and clinical endocrinology, and ensuring the transit of innovative technologies into clinical practice. New laboratories of the World-Class Research Center, will become the place of routine work of a new generation of doctors, who possess not only the basics of clinical work, but also the skills of fundamental researches that will allow them to significantly improve the methods of diagnosis and treatment.