bluuebunny/crossref_metadata_2025 huggingface dataset:
Pengaruh Glukosa Tinggi terhadap Proliferasi, Migrasi dan Ekspresi Gen OCT-4 pada Kultur Sel Dermal Fibroblast Manusia
Authors: Hadi Restu Syamsul , Sandra Yurika
Published: April 2021

Human dermal fibroblasts (HDF) termasuk sel mesenchymal yang diisolasi dari lapisan dermis kulit. HDF berpotensi digunakan untuk pengobatan penyembuhan luka berdasarkan pengobatan regeneratif. Peningkatan konsentrasi glukosa dapat merusak fungsi sel dan menghambat terapi penyembuhan luka. Penelitian ini dilakukan untuk mengkaji pengaruh glukosa tinggi pada proliferasi, migrasi dan ekspresi gen OCT-4 sel HDF sebagai model penyembuhan luka diabetes in vitro. Pada penelitian eksperimental ini, fibroblast diisolasi dari kulit setelah sirkumsisi, kemudian ditumbuhkan dalam medium Minimal Essential Medium (DMEM) Dulbecco lengkap dengan serum 10%. Untuk menguji efek glukosa tinggi pada proliferasi sel HDF dilakukan dengan uji CCK-8. Migrasi sel HDF dievaluasi menggunakan uji scratch-assay. RT-PCR digunakan untuk menentukan ekspresi gen OCT-4.  Hasilnya menunjukkan bahwa glukosa tinggi (25 mM-50 mM) meningkatkan kemampuan proliferasi dan migrasi sel HDF. Efek glukosa tinggi tergantung pada dosis. Perlakuan glukosa pada dosis 75 mM akan menghambat kemampuan pertumbuhan HDF. Ekspresi gen OCT-4 meningkat secara bermakna pada pemberian glukosa dosis 25-50 mM. Hasil penelitian ini memberikan dasar untuk pengembangan terapi dalam kondisi diabetes bahwa terapi sel HDF dapat meningkatkan penyembuhan luka meskipun dalam kondisi glukosa tinggi.
Hubungan Konsumsi Fast Food Dengan Rasio Lingkar Pinggang Panggul pada Mahasiswa Fakultas Kedokteran Universitas YARSI Tahun Pertama dan Tahun Kedua
Authors: Cantika Istri Bela , Widayanti Etty , Zulhamidah Yenni
Published: April 2021

Latar Belakang: Gaya hidup modern saat ini cenderung merugikan karena berdampak buruk pada kesehatan seperti memilih makanan siap saji (instant) atau fast food yang dianggap lebih praktis namun mengandung gizi tidak seimbang sehingga memicu berbagai penyakit ditandai dengan gejala obesitas. Mahasiswa cenderung memiliki gaya hidup modern yang praktis dan kebiasaan mengonsumsi makanan fast food sebagai pilihan utama untuk makan sehari-hari. Obesitas pada remaja penting untuk diperhatikan karena 75% dari mereka cenderung mengalami obesitas pada saat dewasa. Metode: Penelitian ini merupakan penelitian kuantitatif komparatif dengan menggunakan rancangan penelitian cross sectional analitik. Data primer yang didapatkan merupakan hasil sampling dengan metode simple random sampling. Metode korelasi Chi Square dan C Cramers digunakan untuk mengetahui hubungan konsumsi fast food dengan rasio lingkar pinggang panggul. Data penelitian dianalisis secara deskriptif dengan bantuan Microsoft Excel 2010 dan analisis korelasional dengan SPSS Statistics 17.0. Hasil: Berdasarkan uji korelasional dari konsumsi fast food dengan rasio lingkar pinggang panggul menghasilkan nilai signifikansi yang lebih besar dari alpha. Hal ini menunjukkan bahwa tidak terdapat hubungan yang signifikan antara konsumsi fast food dengan rasio lingkar pinggang dan panggul pada mahasiswa Fakultas Kedokteran Universitas YARSI tahun pertama dan tahun kedua. Simpulan: Tidak terdapat adanya hubungan antara konsumsi fast food dengan rasio lingkar pinggang dan panggul pada mahasiswa Fakultas Kedokteran Universitas YARSI tahun pertama dan tahun kedua.
Exploring drift simulations from ocean circulation experiments: application to cod eggs and larval drift
Authors: Melsom A , KØ Kvile , Dagestad KF , Broström G , Langangen Ø
Published: April 2021

Drift models are commonly used to study the transport of early life stages of fish and other marine organisms. Various approaches may be applied to examine the distribution and variability of ocean trajectory pathways. In the present study, we compare results using passive Eulerian tracers and Lagrangian float trajectories that are embedded in numerical models. We supplement this analysis by applying an offline model for drift computations. The contrasts in the results from the various configurations are mainly due to differences in drift depth. Simulations were performed using horizontal resolutions of 4 and 0.8 km. The higher-resolution experiment gives somewhat more realistic results for the drift time from Lofoten to the Tromsøflaket bank at the southwestern entrance of the Barents Sea. Furthermore, differences in results between simulation years are much larger than the differences that arise from the choice of model configuration. Climate variability at high latitudes on a multi-decadal time scale is dominated by large interannual variability superimposed on an underlying moderate warming trend. We conclude that a properly configured offline drift model using hourly or 2-hourly results from a simulation with a horizontal resolution of 1 km or finer is the best approach for investigations of trajectory pathways. The flexibility of an offline drift model is also highly advantageous in biological contexts, as it easily allows for a variety of ways in which behavioural characteristics can be parameterized, including descriptions that are defined after the ocean circulation simulation has been executed.
Comparative Analysis of Rare and Endangered Plants of Hirkan Dendroflora
Authors: Mammadov T. , Rasulova A. , Bagirova S.
Published: April 2021

In the research work has been comparatively analyzed the Hirkan dendroflora and have been collected herbariums of rare and endangered trees and shrubs. There are identified 26 families, 40 genera, 60 species of rare and endangered trees and shrubs naturally spreading areas, distribution of individuals in populations, have been performed tree-ring analysis on old samples. As a result of the observations have been determined, that in the Hirkan flora the majority of species in the areas have been diminished and decreased compared to previous years, many species are in danger of being disappeared. From this point of view by the monitorings of the area were studied threat criteria, the reasons of decline in plant varieties, those plants have been identified based on version of IUCN 3.1. In the research work have been processed out the protection measures, the biological features of species, the causes of change in natural resources.
Influence of the Natural-Geographical Location of Surkhandarya Region on the Placement of Settlements
Authors: Sattarov A.
Published: April 2021

The article examines the influence of natural and geographical factors on the location of settlements in Surkhandarya region from a scientific point of view. The structure of the surface of the Surkhandarya region, the natural geographic tariff, the population and the number of settlements, the historical formation of villages have been studied. In connection with the multinationality of the population in the region, it is natural to divide the village into certain groups, its structural structure and distribution. In mountainous areas, villages are generally more concentrated along streams and springs. Ancient villages consist of seasonal settlements, reflecting the study of the reasons for the location of villages in the highlands, socio-economic, geographical factors, as well as the level of development of the area.
A Study on Lithium Hydroxide Recovery Using Bipolar Membrane Electrodialysis
Authors: Cho Yeonchul , Kim Kihun , Ahn Jaewoo , Lee Jaeheon
Published: April 2021

Bipolar electrodialysis was used in a process of desalting a lithium sulfate solution, converting it to lithium hydroxide and sulfuric acid, and concentrating and recovering them. The effects of the experimental variables such as applied voltage, the concentration of electrode solution, the concentration of raw material solution, volume ratio, and impurity were confirmed. The optimum conditions were investigated by comparing the conversion(%) of lithium hydroxide and sulfuric acid, the process time, and energy consumption. As the applied voltage was increased, the energy consumption tended to increase, but the processing time decreased significantly. As the concentration of lithium sulfate in the raw material solution increased, the conversion(%) of lithium hydroxide decreased. As the concentration of lithium sulfate increased, the energy consumption did not increase linearly, and energy consumption increased significantly. When a raw material solution of 0.5 M Li2SO4 or more is used in the bipolar electrodialysis process, an applied voltage of 25 V is preferable. As the applied voltage increased at a constant process time, the conversion(%) of LiOH and H2SO4 increased. Regarding the effect of the electrode solution concentration, when a 5.0 wt% electrode solution was used rather than a 3.0 wt% electrode solution, energy consumption decreased by more than 10%. When the volume of the raw material solution was increased, the processing time required for desalting increased. By using a low concentration raw material solution, it was confirmed that it was simultaneously possible to recover and concentrate lithium hydroxide and sulfuric acid through volume ratio control. When the raw material solution contained Na as an impurity, it was converted to NaOH with a surface LiOH, and it was not possible to separate the lithium and sodium.
Effect of ZnS/C Mass Ratio on the Morphologies and Luminescence Properties of ZnO Nano/Microstructures Synthesized via Thermal Evaporation of ZnS and C Powder Mixtures
Authors: Lee Geun-Hyoung
Published: April 2021

ZnO nano/microstructures were grown via a simple thermal evaporation process in air at atmospheric pressure. Mixtures of ZnS and carbon powders were used as the sources. The effects of growth temperature and mass ratio of carbon powder to ZnS on the morphologies and luminescence properties of the ZnO nano/microstructures were investigated in this study. When the growth temperature was 1000 oC, ZnO nanowires with a hexagonal wurtzite crystal structure started to be formed and were preferentially grown along the [0001] direction. As the temperature increased to 1200 oC, the crystal growth in the lateral direction perpendicular to the [0001] direction was enhanced, which resulted in a decreasing aspect ratio of the onedimensional ZnO nanowires. When source powders with different mass ratios of ZnS:C=2:1, 1:1 and 1:2 were used to grow ZnO nano/microstructures at 1200 oC, ZnO microrods with wurtzite crystal structure were formed in all the samples. As the mass ratio of carbon powder to ZnS increased, the aspect ratio of ZnO microrods was reduced, which suggests that the carbon powder enhanced the growth of ZnO microrods in the lateral directions. A strong ultraviolet emission band centered at 380 nm was observed in the ZnO nano/microstructures synthesized using the source powders with the mass ratios of ZnS:C=1:1 and 1:2, indicating that the ZnO nano/microstructures had a high crystalline quality.
Definition and Inquiry in Archytas
Authors: Payne Andrew
Published: April 2021

In Archytas of Tarentum, Carl Huffman reconstructs Archytas’ theory of definition by linking definitions to the mathematical study of ratios and proportions. This paper considers whether and how Archytas used definitions and whether he possessed a theory of definition. Our evidence does not support the claim that Archytas has a theory of definition, and his approach to the science of harmonics suggests that he relied on analogies and proportions in the practice of inquiry. We understand sounds and other entities by placing them in a network of relations governed by mathematical proportions. Although he does not seem to have formulated definitions of sound, Archytas pursued inquiry into motion and rest by formulating definitions in such a way that they fit into a larger network of causal explanations.
HISTORY OF RELIGIOUS TOLERATION IN THE RUSSIAN NORTH: RESEARCH ASPECTS
Authors:   Northern (Arctic) Federal University named after M.V. Lomonosov, Arkhangelsk, Russian Federation, KILDYASHOVA TATIANA , PARSHEVA EVGENIYA , SIBIRTSEVA YULIA
Published: April 2021

The formation of religious toleration in the Russian context had a complex and long history. But history of religious toleration in different regions had its own features. The idea of the Russian North as a special example of a multicultural and multi-confessional space has always existed. However, this topic has not received complex studying in the framework of regional studies. The aim of this research is to systematize and analyze the scientific works devoted to the development of the religious situation in the Russian North for identifying traditions of religious toleration and tolerance in this territory. The systematization of the sources is based on the chronological principle up to the beginning of the XX century, and takes into account the three main models of religious life in the region. The analysis showed that the formation of religious toleration in the Russian North was related to the emergence of new religious cultures in the region, which led to their coexistence, and not to the displacement. The official policy of the Orthodox Church and the Russian state towards non-Orthodox and non-Christian people was not always supported by the local community. Moreover, there is evidence for the existence of not only a “passive” form of toleration in the Russian North, but also an “active” form of toleration that was manifested towards non-Orthodox and non-Christian people.
CRIMINAL LEGAL MEANS OF PROVIDING HEALTH CARE DURING THE COVID-19 PANDEMIC
Authors:   NO Moscow bar Association “Unity of Solidarity”, Moscow, Russian Federation, ILIN DANILA
Published: April 2021

The article presents the results of a study of the problems of criminal legal assessment of criminal attacks on the health care system during the COVID-19 pandemic. The social background of such crime and its criminological characteristics are studied. Given the fact that most of criminal law, aimed at preventing crime, reducing the capacity of the state in the fight against novel coronavirus infection treated in depth by the legal and regulatory framework is impeding the spread of the pandemic COVID-19, and analyzed Federal laws, decrees of the President of the Russian Federation, decisions and orders of the Government of the Russian Federation, orders of the Ministry of health of Russia and other state bodies governing the functioning of public authorities, medical institutions and organizations, the rights and obligations of citizens and legal entities, this includes measures for the prevention of this disease in various areas of social life that are additionally regulated during the COVID-19 pandemic. The task of optimizing the criminal law provision of health care during the COVID-19 pandemic is formulated, taking into account the actual situation with the spread of this infection and the practice of countering it. As part of this task, based on a critical analysis of existing approaches in the science of criminal law, we formulate our own concept of crimes that infringe on the health system during the COVID-19 pandemic, characterize the problem, study their legal and social nature, and systematize such crimes. On the basis of the obtained data, a General description of crimes that encroach on the health system during the COVID-19 pandemic is given, their criminal-legal features are considered, theoretical approaches to determining their essence are studied, and the author's position on this issue is formulated. The author's classification of crimes that hinder the provision of health care during the COVID-19 pandemic is given. Groups of such crimes are consistently considered. A General description of their objective and subjective characteristics is given. Proposals for improving the interpretation of the relevant criminal law norms in science and law enforcement practice have been developed, and suggestions for their improvement have been substantiated and formulated. The article is addressed not only to scientists and practitioners of law enforcement agencies, but also to doctors who often work in conditions of a lack of legal knowledge about their rights and obligations, the qualification of certain acts from the point of view of criminal law, the grounds and limits of criminal liability for those that constitute a crime, and algorithms for actions in case of detection of such acts.
PROBLEMS AND PROSPECTS FOR THE ESTABLISHMENT OF A PALESTINIAN STATE IN THE INTERNATIONAL CONTEXT (AMERICAN AND EUROPEAN APPROACHES)
Authors:   Ural Federal University named after B.N. Yeltsin, Yekaterinburg, Russian Federation, RABAYA FUAD MAHMOUD AHMAD
Published: April 2021

The urgency of the issue is determined by the disregard of the international community, especially the United States and its allies, of the will of the Palestinian people to create their own state. The article is devoted to the problem of creating a sovereign Palestinian state. Palestine currently remains a hostage of intermediary States, especially the United States, which does not allow direct negotiations with Israel on the return of the occupied territories, the solution of the refugee issue, the regulation of the status of Jerusalem, and other problems. The Palestinian authority does not have state sovereignty as an integral state entity. The author, after analyzing various projects on the settlement of the Palestinian-Israeli conflict, comes to a disappointing conclusion that it is impossible to achieve the goal of creating a Palestinian state through the assistance of the international community, primarily the United States and the European Union. Due to the current circumstances, it is not possible to hold direct Palestinian-Israeli negotiations. As a conclusion, it is noted that the us monopoly influence on the negotiation process is not productive. To solve this problem, we need a wider range of intermediaries, including international organizations, global and regional actors. Success is possible if the leadership of Israel is inclined to compromise, agreement is reached in Israeli society on the creation of a Palestinian state, and internal contradictions are overcome in the Palestinian society, first of all, the intra-elite split, which further pushes the prospect of the creation of a state of Palestine. The work is based on General scientific research methods and works of Russian and foreign researchers. Empirical data are taken from open sources.
Casting ballots when knowing results
Authors: Araújo Victor , Gatto Malu
Published: April 2021

Access to information about candidates' performance has long stood as a key factor shaping voter behaviour but establishing how it impacts behaviour in real-world settings has remained challenging. In the 2018 Brazilian presidential elections, unpredictable technical glitches caused by the implementation of biometrics as a form of ID led some voters to cast ballots after official tallies started being announced. In addition to providing a source of exogenous variation of information exposure, runoff elections also enable us to distinguish between different mechanisms underlying the impact of information exposure. We find strong support for a vote-switching bandwagon effect: information exposure motivates voters to abandon losing candidates and switch support for the frontrunner---a finding that stands in the second round when only two candidates compete against each other. These findings provide theoretical nuance and stronger empirical support for the mechanisms underpinning the impact of information exposure on voter behaviour.
SISTEM KONTROL UNTUK MENCAPAI ALTITUDE POINT PADA UAV (UNMANNED AERIAL VEHICLE) GLIDER
Authors: Ardila Armanu Putra Bhakti , Tarmukan Tarmukan , Nurcahyo Sidik
Published: April 2021

UAV Glider merupakan pesawat yang didesain dengan bentangan sayap UAV yang memiliki panjang 254cm. Ditinjau dari prinsip aerodinamis, desain tersebut sudah dapat memecah dan melayang di udara dengan baik, dengan catatan perlu adanya kontrol yang baik guna stabilitas terbang dari pesawat tersebut. Dengan desain seperti ini dapat digunakan sebagai pesawat monitoring area dengan ketahanan daya yang lebih lama dibandingkan quadcopter atau drone. UAV Glider menggunakan kontrol Proporsional pada mode pencapaian ketinggian dengan nilai konstanta Kp = 2,5. UAV Glider menggunakan kontroler Arduino Mega dan sensor ketinggian BMP180.  Alat ini bertujuan untuk mencapai ketinggian yang telah ditetapkan dengan sensor BMP180 sebagai referensi untuk pencapaian ketinggian sesuai dengan set point yang ditentukan mulai dari ketinggian 10 meter sampai 21 meter. Saat di udara UAV Glider akan terus berusaha mencapai ketinggian set point, jika set point yang diinginkan tercapai maka langkah selanjutnya UAV Glider akan terbang dengan mempertahankan ketinggian sesuai dengan set point.
New narrow-leafed lupin variety Belorozovy 144
Authors: Ageeva Polina
Published: April 2021

The article presents the description of a new feed middle-ripening narrow-leafed lupin variety. Its vegetation period takes 88–103 days. The average grain yield is 25–30 cwt/ha, the potential one — 40 cwt/ha. The average green mass yield is 340–400 cwt/ha, the potential one — to 6000 cwt/ha. The content of grain raw protein is 33.0–36.0%; the alkaloid content is 0.027–0.050%.
Exosomes Released From Human Bone Marrow–Derived Mesenchymal Stem Cell Attenuate Acute Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation in Mice
Authors: Li Ke-Liang , Li Jin-Yan , Xie Gui-Ling , Ma Xiao-Yan
Published: April 2021

Objective

Mesenchymal stromal cell–derived exosomes have been applied for the treatment of several immune diseases. This study aimed to explore the effect of human bone marrow–derived mesenchymal stem cell (hBMSC)–derived exosomes on acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT).

Methods

hBMSC were cultured, and the culture supernatants were then collected to prepare exosomes using total exosome isolation reagent from Invitrogen. Mouse aGVHD model was established by allogeneic cell transplantation and injected with hBMSC-derived exosomes (Msc-exo) via tail vein. Exosomes from human fibroblast (Fib-exo) were used as the treatment control. The effects of Msc-exo on dendritic cells, CD4+, and CD8+T cells in aGVHD mice were analyzed through flow cytometry. The impact on inflammatory cytokines was tested by ELISA. Besides, the body weight, survival rate, and clinical score of treated mice were monitored.

Results

Msc-exo were successfully prepared. aGVHD mice injected with Msc-exo led to 7–8-fold increase of the CD8α+conventional dendritic cells (cDCs) and CD11b+cDCs compared with the controls. In addition, Msc-exo altered the T help and Treg subpopulation, and decreased the cytotoxicity and proliferation of cytotoxic T cells to favor inflammatory inhibition in aGVHD mice. Mice that received Msc-exo exhibited decreased weight loss and reduced aGVHD clinical score in a time-dependent manner as well as reduced lethality compared with Fib-exo treated or untreated control. Furthermore, the levels of IL-2, TNF-α, and IFN-γ were decreased, as well as the level of IL-10 was increased after Msc-exo treatmentin vivoandin vitro.

Conclusion

hBMSC-derived exosomes could attenuate aGVHD damage and promote the survival of aGVHD mice by regulating the DC and T-cell subpopulation and function, and lead to inhibited inflammatory response in aGVHD mice.
Towards an Automatic Speech-Based Diagnostic Test for Alzheimer’s Disease
Authors: Sadeghian Roozbeh , Schaffer J. David , Zahorian Stephen A.
Published: April 2021

Automatic Speech Recognition (ASR) is widely used in many applications and tools. Smartphones, video games, and cars are a few examples where people use ASR routinely and often daily. A less commonly used, but potentially very important arena for using ASR, is the health domain. For some people, the impact on life could be enormous. The goal of this work is to develop an easy-to-use, non-invasive, inexpensive speech-based diagnostic test for dementia that can easily be applied in a clinician’s office or even at home. While considerable work has been published along these lines, increasing dramatically recently, it is primarily of theoretical value and not yet practical to apply. A large gap exists between current scientific understanding, and the creation of a diagnostic test for dementia. The aim of this paper is to bridge this gap between theory and practice by engineering a practical test. Experimental evidence suggests that strong discrimination between subjects with a diagnosis of probable Alzheimer’s vs. matched normal controls can be achieved with a combination of acoustic features from speech, linguistic features extracted from a transcription of the speech, and results of a mini mental state exam. A fully automatic speech recognition system tuned for the speech-to-text aspect of this application, including automatic punctuation, is also described.
Evaluation of Surgical Gown Textiles for Resistance Against Aerosols: A Preclinical Double-Blind Study
Authors: Barboza Eliane Porto , dos Santos Gustavo Oliveira , Montez Caroline , Sendra Luiza Abreu , Vieira Esio de Oliveira , Carvalho Waldimir , Ferreira Vinicius Farias
Published: April 2021

Personal protective equipment is used to prevent healthcare workers from contaminants. With the advent of COVID-19 pandemic, the use of effective PPE becomes more critical to avoiding infection by SARS-CoV-2. This preclinical double-blind study evaluated the performance of surgical gown textiles for penetration resistance against aerosols. The different textiles were divided into seven groups: (1) SMS PP OE Phobic; (2) Laminated Phobic; (3) Medical Barrier; (4) Trilayer Fabric; (5) Impermeable gown; (6) Impermeable with heat sealing tape; and (7) Clean Wear. All groups were exposed to aerosol-generating procedure for 5 min, according to Barboza et al. 2020. All measurements were recorded and exported to a datasheet for analysis using SPSS software. The groups showed significant differences (p < 0.01). Groups 2, 3, 4, 5, and 6 proved to be effective barriers against aerosols and presented a constant behavior. Groups 1 and 7 showed pigmented areas of 13.05 and 48.23%, respectively, suggesting that, in the present test model, these water-repellent and antimicrobial fabrics were not effective barriers against 5-min aerosols generated by a high-speed dental handpiece. Polyethylene or polyurethane laminated fabrics were efficient against 5-min aerosols. The SMS textile, globally used for surgical gowns, and the cotton fabric, impregnated with nanoparticles, were not effective barriers. The breathability and comfort of these textiles should be tested in future studies. Healthcare workers should be aware of the exact specifications of their surgical gown textiles.
Modern India and Dietary Calcium Deficiency—Half a Century Nutrition Data—Retrospect–Introspect and the Road Ahead
Authors: Harinarayan Chittari Venkata , Akhila Harinarayan , Shanthisree Edara
Published: April 2021

Calcium and vitamin D are inseparable nutrients required for bone health. In the past half a century, the dietary calcium intake of rural, tribal, and urban India has declined. Though India is the largest producer of milk and cereals, the major source of calcium in India is through non-dairy products. The highest intake of cereals and lowest intake of milk & milk products was observed in rural and tribal subjects whereas, the intake of cereals, milk & milk products were similar in both urban and metropolitan subjects. One of the reasons for lower calcium intake was the proportion of calcium derived from dairy sources. Over the past half a century, the average 30-day consumption of cereals in the rural and urban population has declined by 30%. The Per Capita Cereal Consumption (PCCC)has declined despite sustained raise in Monthly Per capita Consumption Expenditure (MPCE) in both rural and urban households. The cereal consumption was the highest in the lowest income group, despite spending smaller portion of their income, as cereals were supplied through public distribution system (PDS). About 85% of the Indian population are vitamin D deficient despite abundant sunlight. Dietary calcium deficiency can cause secondary vitamin D deficiency. Though India as a nation is the largest producer of milk, there is profound shortage of calcium intake in the diet with all negative consequences on bone health. There is a decline in dietary calcium in the background of upward revision of RDI/RDA. There is a gap in the production-consumption-supply chain with respect to dietary calcium. To achieve a strong bone health across India, it is imperative to have population based strategies addressing different segments including supplementing dietary/supplemental calcium in ICDS, mid-day-meals scheme, public distribution system, educational strategies. Other measures like mass food fortification, biofortification, bioaddition, leveraging digital technologies, investments from corporate sector are some measures which can address this problem. India is a vast country with diverse social, cultural and dietary habits. No single measure can address this problem and requires a multi-pronged strategic approach to tackle the dietary calcium deficiency to achieve strong bone health while solving the problem of nutritional deficiency.
Non-Alcoholic Fatty Liver Disease in Obese Youth With Insulin Resistance and Type 2 Diabetes
Authors: Scapaticci Serena , D’Adamo Ebe , Mohn Angelika , Chiarelli Francesco , Giannini Cosimo
Published: April 2021

Currently, Non-Alcoholic Fatty Liver Disease (NAFLD) is the most prevalent form of chronic liver disease in children and adolescents worldwide. Simultaneously to the epidemic spreading of childhood obesity, the rate of affected young has dramatically increased in the last decades with an estimated prevalence of NAFLD of 3%–10% in pediatric subjects in the world. The continuous improvement in NAFLD knowledge has significantly defined several risk factors associated to the natural history of this complex liver alteration. Among them, Insulin Resistance (IR) is certainly one of the main features. As well, not surprisingly, abnormal glucose tolerance (prediabetes and diabetes) is highly prevalent among children/adolescents with biopsy-proven NAFLD. In addition, other factors such as genetic, ethnicity, gender, age, puberty and lifestyle might affect the development and progression of hepatic alterations. However, available data are still lacking to confirm whether IR is a risk factor or a consequence of hepatic steatosis. There is also evidence that NAFLD is the hepatic manifestation of Metabolic Syndrome (MetS). In fact, NAFLD often coexist with central obesity, impaired glucose tolerance, dyslipidemia, and hypertension, which represent the main features of MetS. In this Review, main aspects of the natural history and risk factors of the disease are summarized in children and adolescents. In addition, the most relevant scientific evidence about the association between NAFLD and metabolic dysregulation, focusing on clinical, pathogenetic, and histological implication will be provided with some focuses on the main treatment options.
Immune Subtyping in Latent Tuberculosis
Authors: Banerjee Ushashi , Baloni Priyanka , Singh Amit , Chandra Nagasuma
Published: April 2021

Latent tuberculosis infection (LTBI) poses a major roadblock in the global effort to eradicate tuberculosis (TB). A deep understanding of the host responses involved in establishment and maintenance of TB latency is required to propel the development of sensitive methods to detect and treat LTBI. Given that LTBI individuals are typically asymptomatic, it is challenging to differentiate latently infected from uninfected individuals. A major contributor to this problem is that no clear pattern of host response is linked with LTBI, as molecular correlates of latent infection have been hard to identify. In this study, we have analyzed the global perturbations in host response in LTBI individuals as compared to uninfected individuals and particularly the heterogeneity in such response, across LTBI cohorts. For this, we constructed individualized genome-wide host response networks informed by blood transcriptomes for 136 LTBI cases and have used a sensitive network mining algorithm to identify top-ranked host response subnetworks in each case. Our analysis indicates that despite the high heterogeneity in the gene expression profiles among LTBI samples, clear patterns of perturbation are found in the immune response pathways, leading to grouping LTBI samples into 4 different immune-subtypes. Our results suggest that different subnetworks of molecular perturbations are associated with latent tuberculosis.
GVHD Prophylaxis 2020
Authors: Gooptu Mahasweta , Antin Joseph Harry
Published: April 2021

Graft-vs. host disease (GVHD), both acute and chronic are among the chief non-relapse complications of allogeneic transplantation which still cause substantial morbidity and mortality despite significant advances in supportive care over the last few decades. The prevention of GVHD therefore remains critical to the success of allogeneic transplantation. In this review we briefly discuss the pathophysiology and immunobiology of GVHD and the current standards in the field which remain centered around calcineurin inhibitors. We then discuss important translational advances in GVHD prophylaxis, approaching these various platforms from a mechanistic standpoint based on the pathophysiology of GVHD including in-vivo and ex-vivo T-cell depletion alongwith methods of selective T-cell depletion, modulation of T-cell co-stimulatory pathways (checkpoints), enhancing regulatory T-cells (Tregs), targeting T-cell trafficking as well as cytokine pathways. Finally we highlight exciting novel pre-clinical research that has the potential to translate to the clinic successfully. We approach these methods from a pathophysiology based perspective as well and touch upon strategies targeting the interaction between tissue damage induced antigens and T-cells, regimen related endothelial toxicity, T-cell co-stimulatory pathways and other T-cell modulatory approaches, T-cell trafficking, and cytokine pathways. We end this review with a critical discussion of existing data and novel therapies that may be transformative in the field in the near future as a comprehensive picture of GVHD prophylaxis in 2020. While calcineurin inhibitors remain the standard, post-transplant eparinsphamide originally developed to facilitate haploidentical transplantation is becoming an attractive alternative to traditional calcinuerin inhibitor based prophylaxis due to its ability to reduce severe forms of acute and chronic GVHD without compromising other outcomes, even in the HLA-matched setting. In addition T-cell modulation, particularly targeting some important T-cell co-stimulatory pathways have resulted in promising outcomes and may be a part of GVHD prophylaxis in the future. Novel approaches including targeting early events in GVHD pathogenesis such as interactions bvetween tissue damage associated antigens and T-cells, endothelial toxicity, and T-cell trafficking are also promising and discussed in this review. GVHD prophylaxis in 2020 continues to evolve with novel exicitng therapies on the horizon based on a more sophisticated understanding of the immunobiology of GVHD.
Delineating the Association Between Soluble CD26 and Autoantibodies Against G-Protein Coupled Receptors, Immunological and Cardiovascular Parameters Identifies Distinct Patterns in Post-Infectious vs. Non-Infection-Triggered Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Authors: Szklarski Marvin , Freitag Helma , Lorenz Sebastian , Becker Sonya C. , Sotzny Franziska , Bauer Sandra , Hartwig Jelka , Heidecke Harald , Wittke Kirsten , Kedor Claudia , Hanitsch Leif G. , Grabowski Patricia , Sepúlveda Nuno , Scheibenbogen Carmen
Published: April 2021

Soluble cluster of differentiation 26 (sCD26) has a wide range of enzymatic functions affecting immunological, metabolic and vascular regulation. Diminished sCD26 concentrations have been reported in various autoimmune diseases and also in Myalgic Encephalomyelitis/Chronic fatigue syndrome (ME/CFS). Here we re-evaluate sCD26 as a diagnostic marker and perform a comprehensive correlation analysis of sCD26 concentrations with clinical and paraclinical parameters in ME/CFS patients. Though this study did find significantly lower concentrations of sCD26 only in the female cohort and could not confirm diagnostic suitability, results from correlation analyses provide striking pathomechanistic insights. In patients with infection-triggered onset, the associations of low sCD26 with elevated autoantibodies (AAB) against alpha1 adrenergic (AR) and M3 muscarinic acetylcholine receptors (mAChR) point to a pathomechanism of infection-triggered autoimmune-mediated vascular and immunological dysregulation. sCD26 concentrations in infection-triggered ME/CFS were found to be associated with activated T cells, liver enzymes, creatin kinase (CK) and lactate dehydrogenase (LDH) and inversely with Interleukin-1 beta (IL-1b). Most associations are in line with the known effects of sCD26/DPP-4 inhibition. Remarkably, in non-infection-triggered ME/CFS lower sCD26 in patients with higher heart rate after orthostatic challenge and postural orthostatic tachycardia syndrome (POTS) suggest an association with orthostatic regulation. These findings provide evidence that the key enzyme sCD26 is linked to immunological alterations in infection-triggered ME/CFS and delineate a different pathomechanism in the non-infectious ME/CFS subset.
The Evolving Landscape of Biomarkers in Celiac Disease: Leading the Way to Clinical Development
Authors: Smithson Glennda , Siegelman Jenifer , Oki Toshihiko , Maxwell Joseph R. , Leffler Daniel A.
Published: April 2021

Celiac disease is a common immune-mediated disease characterized by abnormal T-cell responses to gluten. For many patients, symptoms and intestinal damage can be controlled by a gluten-free diet, but, for some, this approach is not enough, and celiac disease progresses, with serious medical consequences. Multiple therapies are now under development, increasing the need for biomarkers that allow identification of specific patient populations and monitoring of therapeutic activity and durability. The advantage of identifying biomarkers in celiac disease is that the underlying pathways driving disease are well characterized and the histological, cellular, and serological changes with gluten response have been defined in gluten challenge studies. However, there is room for improvement. Biomarkers that measure histological changes require duodenal biopsies and are invasive. Less invasive peripheral blood cell and cytokine biomarkers are transient and dependent upon gluten challenge. Here, we discuss established biomarkers and new approaches for biomarkers that may overcome current limitations.
An Exploratory Study of Telomere Length in the Deep-Sea Shark, Etmopterus granulosus
Authors: Nehmens Melissa C. , Varney Rebecca M. , Janosik Alexis M. , Ebert David A.
Published: April 2021

The history of elasmobranch ageing highlights the difficulty of age estimation in animals lacking ossified structures. Ageing techniques are numerous, yet all are limited by difficulties of validation and verification and inherent subjectivity. Sample scarcity further hinders progress as limited samples cannot be risked on exploratory techniques. This study explored the use of genetic analysis of telomeres as a method of age determination in a deep-sea shark, Etmopterus granulosus, a representative of a poorly studied taxon with regard to ageing due to sample scarcity. Telomeres were amplified in 39 individuals with qPCR, compared across samples, and were found to differ across size classes. More work is needed to determine whether telomeres consistently correlate with size class across elasmobranchs. However, telomeres offer easily obtainable data that can be combined with traditional methods to provide additional points of comparison for elasmobranch biology. Our results underscore the importance of expanding current ageing methods and highlight a necessary distinction between chronological and biological ages when describing elasmobranch populations.
Assessment of the Safety and Therapeutic Benefits of Convalescent Plasma in COVID-19 Treatment: A Systematic Review and Meta-Analysis
Authors: Barreira Daniela Ferreira , Lourenço Rita Adubeiro , Calisto Rita , Moreira-Gonçalves Daniel , Santos Lúcio Lara , Videira Paula Alexandra
Published: April 2021

Background: The coronavirus disease (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), prompted a global health crisis, with no available specific treatments. Convalescent plasma (CP) with neutralizing antibodies could be a promising therapeutic approach to reduce mortality.

Objectives: To evaluate the therapeutic potential of CP for COVID-19 and to assess its safety and efficacy in reducing the patients' mortality.

Methods: We retrieved clinical trial references from multiple Databases (e.g., PubMed, B-On, SCOPUS), for complete studies until November 26th 2020. We included Randomized controlled trials (RCT) and controlled non-randomized trials (CNRT), that assessed the efficacy of CP to treat hospitalized COVID-19 patients. Trials were included regardless of concomitant medications in the intervention's arms. Eleven trials met our eligibility criteria. This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. We defined a methodological protocol to extract and evaluate all pertinent baseline demographics and interventions' characteristics from trials. The primary outcomes were the safety profile of CP, measured by the type, frequency and severity of adverse events, and CP effectiveness in reducing mortality, measured by the number of deaths registered for this therapy.

Results: We assessed 11 trials (5 RCT and 6 CNRT) with 3,098 participants, of whom 923 patients were treated with CP. Only 32 (3.5%) of the treated patients suffered adverse events (from which 9.4% serious transfusion-related adverse events). The overall mortality rates were significantly decreased by CP administration {risk ratio (RR) 0.71, p = 0.005, 95% confidence interval (Cl) [0.57–0.90]}, with low heterogeneity. In the sub-analysis by period of transfusion, CP transfusion within a week of hospitalization contributed to diminished mortality rate (RR = 0.71, p = 0.03, 95%Cl [0.53–0.96]). CP therapy also led to significantly reduced viral loads at 72 h after transfusion (RR = 0.61, p = 0.04, 95%Cl [0.38–0.98]), despite high heterogeneity due to disease severity.

Conclusion: This meta-analysis established CP as a safe and potentially effective therapy for COVID-19, decreasing the mortality rates and promoting a swift viral clearance. Further studies are necessary to provide stronger evidence.
Development of a Nomogram to Predict 28-Day Mortality of Patients With Sepsis-Induced Coagulopathy: An Analysis of the MIMIC-III Database
Authors: Lu Zongqing , Zhang Jin , Hong Jianchao , Wu Jiatian , Liu Yu , Xiao Wenyan , Hua Tianfeng , Yang Min
Published: April 2021

Background: Sepsis-induced coagulopathy (SIC) is a common cause for inducing poor prognosis of critically ill patients in intensive care unit (ICU). However, currently there are no tools specifically designed for assessing short-term mortality in SIC patients. This study aimed to develop a practical nomogram to predict the risk of 28-day mortality in SIC patients.

Methods: In this retrospective cohort study, we extracted patients from the Medical Information Mart for Intensive Care III (MIMIC-III) database. Sepsis was defined based on Sepsis 3.0 criteria and SIC based on Toshiaki Iba's criteria. Kaplan–Meier curves were plotted to compare the short survival time between SIC and non-SIC patients. Afterward, only SIC cohort was randomly divided into training or validation set. We employed univariate logistic regression and stepwise multivariate analysis to select predictive features. The proposed nomogram was developed based on multivariate logistic regression model, and the discrimination and calibration were verified by internal validation. We then compared model discrimination with other traditional severity scores and machine learning models.

Results: 9432 sepsis patients in MIMIC III were enrolled, in which 3280 (34.8%) patients were diagnosed as SIC during the first ICU admission. SIC was independently associated with the 7- and 28-day mortality of ICU patients. K–M curve indicated a significant difference in 7-day (Log-Rank: P < 0.001 and P = 0.017) and 28-day survival (Log-Rank: P < 0.001 and P < 0.001) between SIC and non-SIC groups whether the propensity score match (PSM) was balanced or not. For nomogram development, a total of thirteen variables of 3,280 SIC patients were enrolled. When predicted the risk of 28-day mortality, the nomogram performed a good discrimination in training and validation sets (AUROC: 0.78 and 0.81). The AUROC values were 0.80, 0.81, 0.71, 0.70, 0.74, and 0.60 for random forest, support vector machine, sequential organ failure assessment (SOFA) score, logistic organ dysfunction score (LODS), simplified acute physiology II score (SAPS II) and SIC score, respectively, in validation set. And the nomogram calibration slope was 0.91, the Brier value was 0.15. As presented by the decision curve analyses, the nomogram always obtained more net benefit when compared with other severity scores.

Conclusions: SIC is independently related to the short-term mortality of ICU patients. The nomogram achieved an optimal prediction of 28-day mortality in SIC patient, which can lead to a better prognostics assessment. However, the discriminative ability of the nomogram requires validation in external cohorts to further improve generalizability.
Prevalence, Risk Factors, and Comorbidities of Obstructive Sleep Apnea Risk Among a Working Population in Kuwait: A Cross-Sectional Study
Authors: Al-Qattan Husain , Al-Omairah Hamad , Al-Hashash Khaled , Al-Mutairi Fahad , Al-Mutairat Mohammad , Al-Ajmi Mohammad , Mohammad Anwar , Alterki Abdulmohsen , Ziyab Ali H.
Published: April 2021

Background: Obstructive sleep apnea (OSA) affects a considerable proportion of adults globally and is associated with elevated morbidity and mortality. Given the lack of epidemiologic data on the burden of OSA in Kuwait, this study sought to estimate its prevalence, associated risk factors, and comorbid conditions among a working population in Kuwait.

Methods: This was a cross-sectional study of a sample of working adults (n = 651) from public institutions in Kuwait. High/low risk for OSA was ascertained according to the Berlin Questionnaire criteria. Participants self-reported their coexisting health conditions. Associations were assessed using Poisson regression with robust variance estimation; adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs) were estimated.

Results: Overall, 20.0% (130/651) of participants were classified as being at high risk for OSA, with more male than female subjects being at high risk (24.0% [56/233] vs. 17.7% [74/418], P = 0.053), though this difference did not gain statistical significance. Moreover, a high risk for OSA was more common among older and obese subjects. Factors associated with increased prevalence of a high risk for OSA included current smoking status (aPR = 1.58, 95% CI: 1.02–2.06), longer hours spent watching television (1.76, 1.10–2.81), and lower self-perceived physical health (2.11, 1.15–3.87). However, decreasing trends in the prevalence of high risk for OSA were observed with frequent engagement in vigorous physical activity and longer nightly sleep duration. Compared to those at a low risk for OSA, the subjects at high risk for OSA were more likely to have insomnia disorder (2.83, 1.81–4.41), diabetes (1.94, 1.15–3.27), hypertension (3.00, 1.75–5.16), and depression (4.47, 1.80–11.08).

Conclusion: This study estimated that 1/5 of working adults in Kuwait were at high risk for OSA, and the prevalence varied according to personal characteristics and lifestyle factors. Also, a high risk for OSA classification was associated with multiple comorbid health conditions.