bluuebunny/crossref_metadata_2025 huggingface dataset:
Pelatihan Keterampilan Menjahit Masker Kain Dalam Memanfaatkan Peluang Bisnis Era Pandemi Covid-19
Authors: Emilda Emilda , Wulandari Try , Lazuarni Shafiera
Published: May 2021

Abstract: Nowadays, medical mask is difficult to find in several pharmacies in Palembang. This situation could be a promising business opportunity during the Covid-19 epidemic. The target partners in this activity are residents of Gang Sei Saling, Siring Agung Sub-district, Ilir Barat 1 District, Palembang. This PkM activity aims to provide cloth mask sewing skills to take advantage of business opportunities during the Covid-19 pandemic. The method used in this activity is the training method. The sewing training activities consist of two types of activities, namely the presentation of sewing theory and practical training on sewing cloth masks. The presentation is going to explain about sewing theory, sewing concepts, tools and equipment needed in sewing, types and selection of fabrics. Meanwhile, training for sewing cloth masks, undoing the practice of operating a sewing machine, making cloth mask patterns, cutting patterns, sewing cloth masks, and finishing. In this PkM activity, participants not only provided skills in sewing cloth masks, but also at the finishing step such as folding and packaging. Keywords: cloth masks; sewing; training  Abstrak: Dengan adanya kelangkaan masker medis yang mulai sulit ditemukan di apotek     Palembang, hal ini menjadi peluang bisnis di masa pendemi Covid – 19. Target mitra dalam kegiatan ini adalah Warga Gang Sei Saling, kelurahan Siring Agung, kecamatan Ilir Barat 1, Palembang. Kegiatan PkM ini bertujuan memberikan keterampilan menjahit masker kain untuk memanfaatkan peluang bisnis pada saat pandemi Covid – 19. Metode yang digunakan dalam kegiatan ini adalah metode pelatihan. Kegiatan pelaksanaan pelatihan menjahit ini terdiri dari dua jenis kegiatan yaitu pemaparan teori menjahit dan pelatihan praktek menjahit masker kain. Pemaparan teori menjahit terdiri konsep menjahit, peralatan dan perlengkapan yang dibutuhkan dalam menjahit, dan jenis dan pemilihan kain. Sedangkan kegiatan pelatihan praktek menjahit masker kain terdiri dari praktek mengoperasikan mesin jahit,membuat pola masker kain, menggunting pola, menjahit masker kain, dan finishing. Dalam kegiatan PkM ini, peserta tidak hanya diberikan keterampilan menjahit masker kain, tetapi juga hingga tahap finishing seperti melipat dan mengemas masker kain.Kata kunci: masker kain; menjahit; pelatihan
Implementation of the Bayes Method for diagnosing tuberculosis
Authors: Sari Nina , Sihombing Volvo , Irmayani Deci
Published: May 2021

Tuberculosis is an infection caused by acid-resistant bacilli or an infectious disease that can attack anyone through the air is also a dangerous infectious disease besides it is also a chronic or chronic disease that can strike between the ages of 15-35 years. The purpose of this study is to help prevent tuberculosis by implementing an expert system using the Bayes method. The method used in this research includes identifying problems faced in the medical world for treating tuberculosis, analyzing the problem, then formulating the problem and applying an expert system with the Bayes method to solve the problems that are obtained, the next stage is designing an application as needed, testing the application with the aim of knowing the success rate of the system. The implementation of the Bayes method in diagnosing tuberculosis is found. The result is that the calculation process using the Bayes method is based on the symptoms experienced by the patient. It can be seen that the patient is "most likely" to have pulmonary tuberculosis with a confidence value of 0.64 or 64%. From the results of the research conducted, it can be concluded that in diagnosing Tuberculosis by using the Bayes method expert system, it can help medical parties handle cases more quickly in terms of recognizing the symptoms of Tuberculosis so that people quickly know the disease they are experiencing.
Pharmacotherapy of pandemic and post-pandemic stress-related mental disorders
Authors: Heitzman Janusz
Published: May 2021

Objectives. The outbreak of the COVID-19 pandemic at the end of 2019, caused by the SARS-CoV-2 virus, manifested in the form of severe acute respiratory failure, also results in a reduced mental condition and resilience on an unprecedented scale and with consequences that are difficult to assess.
Literature review. It has been observed that the clinical picture of mental disorders manifested in reaction to confrontation with the pandemic trauma does not strictly coincide with the diagnostic criteria of commonly used diagnoses, i.e. acute stress reaction (ASR), acute stress disorder (ASD), and post-traumatic stress disorder (PTSD). In the case of PTSD in particular, it is difficult to adopt unambiguous criteria for a precise diagnosis during the ongoing pandemic. The occurrence of mental disorders in response to pandemic trauma depends on individual risk factors, the nature of traumatic stress, and environmental factors.
Conclusions. The phenomenon of a widespread population confrontation with the pandemic, more than the intensity of the stressor itself, prompts us to recall the possibility of effective pharmacological support in already existing pandemic mental disorders and to prepare for pharmacological intervention against mental disorders that will manifest themselves after the pandemic has expired.
From Analogue to Digital Banking: Developments in the European Union from 2007 to 2019
Authors: Menrad Michael , Varga József
Published: May 2021

Research on banking regularly assumes that digitalisation has an impact on banking. This blanket assumption is not erroneous, but it is too inaccurate, too undifferentiated and probably only applies in the long term. Results of this study show that the customers’ habits and requirements and thus the willingness to accept digital technologies in the banking sector are changing within a significantly different speed. The spread ranges from almost complete use, as in Scandinavia, dynamic development, as in the Czech Republic and Greece, to almost complete rejection, as in Bulgaria and Romania. This paper examines and demonstrates the influence of various socio-demographic and emotional characteristics on the use of digital media. Shifts in customer behaviours are revealed and discrepancies are identified by time series analyses and factor analyses. The results reveal the forthcoming death of the bank branch network accompanied by a regionally varying acceptance of Internet and mobile banking. This area of tension requires banks to have a good understanding of customer requirements regarding the demand for digitisation in order to avoid misguided decisions. However, the bank’s side in the adoption process of new technologies by customers has been neglected by scientific studies so far. In order to measure the state of digitisation of banking services, a comparison equation is presented that allows banks to be benchmarked in terms of the degree of digitisation and enables banks to dynamically track changes in their customer portfolios.
Reviews of Sustainable Rural Development in the Scope of Building New Rural Areas in Vietnam
Authors: Thuy Nguyen Thi Thu
Published: May 2021

In Vietnam, rural area is a region for living and working of a rural resident community, including mainly farmers. It is a region of agricultural production (by the general meaning). Besides, there are manufacturing activities and service, but priority is given to agriculture and rural community. Meanwhile, the rural density is lower than urban density. Vietnam introduced its development programme “Building new rural areas”, which program aims at finding a concept of sustainable development in rural areas in order to emerge the role of sustainable development toward the National direction for local strategies and to ensure sustainable rural development. This paper is a work at the scope of reviews and literature available worldwide in development policies and programmes on sustainable rural development. It compares the dimensions of these policies and programmes on the basis of definitions, methodology and practical framework applied in order to identify a promotion for building new rural areas in disciplines, and especially supply a background for data analyses of the Vietnamese case in the National Target Programme “Building new rural areas during the period 2011-2015”.
ARTICULATE STORYLINE: SEBUAH PENGEMBANGAN MEDIA PEMBELAJARAN INTERAKTIF PADA MATERI SEL
Authors: Suhailah Fina , Muttaqin Muhammad , Suhada Idad , Jamaluddin Dindin , Paujiah Epa
Published: May 2021

Kendala yang terjadi pada saat mengajar  yaitu kurangnya media untuk diperlihatkan ke siswa tentang materi sel dan kurangnya sumber daya dalam pemanfaatan fasilitas yang tersedia di MA Pondok Quran di era pandemi seperti sekarang. Penelitian ini bertujuan untuk mengembangkan desain media, mengetahui kelayakan dan respon siswa terhadap media pembelajaran interaktif berbasis Articulate Storyline pada materi sel. Rancangan penelitian menggunakan metode Research and Development (RD) dengan model penelitian 4D dimodifikasi menjadi 3D yang dikembangkan oleh Sivasailam Thiagarajan, Dorothy S. Semmel dan Melvyn I. Semmel. Sumber data pada penelitian ini adalah validator yaitu ahli media dan ahli materi, guru bidang mata pelajaran biologi dan siswa kelas XI IPA MA Pondok Quran. Instrumen pengumpulan data menggunakan lembar validasi ahli media, lembar validasi ahli materi dan angket respon siswa. Teknik pengumpulan data menggunakan validasi ahli media, validasi ahli materi dan angket. Teknik analisis data menggunakan uji kelayakan dan respon siswa terhadap media pembelajaran interaktif berbasis Articulate Storyline. Hasil penelitian menunjukkan bahwa penelitian pengembangan ini menghasilkan media pembelajaran interaktif berbasis Articulate Storyline dengan link akses https://bit.ly/MediaInteraktifSelXI. Uji kelayakan media pembelajaran interaktif berbasis Articulate Storyline pada materi sel diperoleh hasil 85,28%. Respon siswa terhadap media pembelajaran mendapat hasil 83,6% dengan kriteria sangat positif. Hal ini dapat disimpulkan bahwa media pembelajaran interaktif berbasis Articulate Storyline sangat layak digunakan sebagai media belajar yang efektif untuk siswa kelas XI MIPA MA Pondok Quran.
Building a Bigger Table: Networking 101 For Graduate Students
Authors: Kim Seo-young Silvia , Lebovits Hannah , Shugars Sarah
Published: May 2021

Although the importance of networking is often emphasized to graduate students, straightforward guidance on how to approach this task is typically reliant on individual advisors both knowing and demystifying the discipline's hidden and informal practices. This article provides concrete, point-by-point tips for both graduate students and their supporters, building on our experiences creating an online communication forum for early-career scholars on the market. Specifically, we suggest a model of community networking focused on robust, cross-rank engagement along dimensions of similar experiences and similar interests. Community networking aims to move beyond individuals angling to get a seat at the table and instead builds a bigger, more inclusive table. While junior scholars must primarily focus on their research rather than expansive service commitments, community networking is ultimately both a service to the discipline and a fruitful strategy for raising one's profile and finding coauthors, colleagues, friends, and allies.
UK magazine advertising portrayals of older adults: a longitudinal, content analytic, and a social semiotic lens
Authors: Ylänne Virpi
Published: May 2021

The focus of this article is the depiction of older adults in UK magazine advertising. Theoretically located in the broad area of cultural gerontology, with its central focus on culturally constitutive meaning of age(ing) (e.g. Twigg & Martin 2015), it applies social semiotic categories (Kress & van Leeuwen 1996, 2004) and draws on critical discourse analytic insights in investigating persistent trends in advertising images of older adults. These are linked with the role of advertising media in constructing and contributing to specific social “imaginary” or “imagination” of later life. A content analytic comparison between two corpora of adverts (221 ads from 1999 to 2004 and 313 ads from 2011 to 2016) reveals only minor changes over time. These include relative consistency in the product categories linked with older models, the adverts predominantly targeting older adults, but a decline in humorous portrayals. A semiotically oriented analysis of a subset of adverts further examines their compositional and affective dimensions, in addition to representational qualities. This uncovers strategies that are in line with aspirational third age discourse and imagery, but which also contribute to the marginalisation of older adults via a restricted portrayal of later life(styles) and can also be seen to problematise “ageless” depictions.
Mobile Monitoring of Air Pollution Reveals Spatial and Temporal Variation in an Urban Landscape
Authors: Cummings Lucas E. , Stewart Justin D. , Reist Radley , Shakya Kabindra M. , Kremer Peleg
Published: May 2021

Urban air pollution poses a major threat to human health. Understanding where and when urban air pollutant concentrations peak is essential for effective air quality management and sustainable urban development. To this end, we implement a mobile monitoring methodology to determine the spatiotemporal distribution of particulate matter (PM) and black carbon (BC) throughout Philadelphia, Pennsylvania and use hot spot analysis and heatmaps to determine times and locations where pollutant concentrations are highest. Over the course of 12 days between June 27 and July 29, 2019, we measured air pollution concentrations continuously across two 150 mile (241.4 km) long routes. Average daily mean concentrations were 11.55 ± 5.34 μg/m3 (PM1), 13.48 ± 5.59 μg/m3 (PM2.5), 16.13 ± 5.80 μg/m3 (PM10), and 1.56 ± 0.39 μg/m3 (BC). We find that fine PM size fractions (PM2.5) constitute approximately 84% of PM10 and that BC comprises 11.6% of observed PM2.5. Air pollution hotspots across three size fractions of PM (PM1, PM2.5, and PM10) and BC had similar distributions throughout Philadelphia, but were most prevalent in the North Delaware, River Wards, and North planning districts. A plurality of detected hotspots found throughout the data collection period (30.19%) occurred between the hours of 8:00 AM–9:00 AM.
Novel Truncating and Missense Variants in SEMA6B in Patients With Early-Onset Epilepsy
Authors: Xiaozhen Song , Fan Yuan , Fang Yuan , Xiaoping Lan , Jia Jia , Wuhen Xu , Xiaojun Tang , Jun Shen , Yucai Chen , Hong Zhang , Guang He , Shengnan Wu
Published: May 2021

Progressive myoclonic epilepsy (PME) is a rare neurodegenerative disease, characterized by myoclonic seizures and tonic clonic seizures, with genetical and phenotypical heterogeneity. The semaphorin 6B (SEMA6B) gene has been recently reported a causal gene of PME. Independent studies are warranted to further support these findings. Here we report that one nonsense variant in NM_032108.3 exon17 c.2056C > T (p.Gln686∗) and one missense variant in exon14 c.1483G > T (p.Gly495Trp) of SEMA6B, both occurring de novo, underlie early-onset epilepsy with variable severity and different response to treatment in two patients. In vitro analyses have demonstrated that the nonsense variant, p.Gln686∗, results in a truncated protein with remarkably increased expression compared to that of the wild type. The truncated protein presented more homogeneous and failed to locate in the plasma membrane. The missense variant p.Gly495Trp affects evolutionarily conserved amino acid and is located in the sema domain, a key functional domain of SEMA6B. It was predicted to perturb the SEMA6B function by altering the tertiary structure of mutant protein, although neither change of protein length and expression nor difference of cellular distribution was observed. Co-immunoprecipitation studies have demonstrated that both variants influence protein binding of SEMA6B and PlxnA2 with varying degrees. Our results provide further evidence to support the initial findings of SEMA6B being causal to epilepsy and indicate that mediating Semaphorin/Plexin signaling is the potential mechanism of the SEMA6B-related disease.
Adhesion Process of Biomimetic Myelin Membranes Triggered by Myelin Basic Protein
Authors: Krugmann Benjamin , Koutsioubas Alexandros , Haris Luman , Micciulla Samantha , Lairez Didier , Radulescu Aurel , Förster Stephan , Stadler Andreas M.
Published: May 2021

The myelin sheath—a multi-double-bilayer membrane wrapped around axons—is an essential part of the nervous system which enables rapid signal conduction. Damage of this complex membrane system results in demyelinating diseases such as multiple sclerosis (MS). The process in which myelin is generatedin vivois called myelination. In our study, we investigated the adhesion process of large unilamellar vesicles with a supported membrane bilayer that was coated with myelin basic protein (MBP) using time-resolved neutron reflectometry. Our aim was to mimic and to study the myelination process of membrane systems having either a lipid-composition resembling that of native myelin or that of the standard animal model for experimental autoimmune encephalomyelitis (EAE) which represents MS-like conditions. We were able to measure the kinetics of the partial formation of a double bilayer in those systems and to characterize the scattering length density profiles of the initial and final states of the membrane. The kinetics could be modeled using a random sequential adsorption simulation. By using a free energy minimization method, we were able to calculate the shape of the adhered vesicles and to determine the adhesion energy per MBP. For the native membrane the resulting adhesion energy per MBP is larger than that of the EAE modified membrane type. Our observations might help in understanding myelination and especially remyelination—a process in which damaged myelin is repaired—which is a promising candidate for treatment of the still mostly incurable demyelinating diseases such as MS.
Modulating Target Protein Biology Through the Re-mapping of Conformational Distributions Using Small Molecules
Authors: Lawson Alastair D. G. , MacCoss Malcolm , Baeten Dominique L. , Macpherson Alex , Shi Jiye , Henry Alistair J.
Published: May 2021

Over the last 10 years considerable progress has been made in the application of small molecules to modulating protein-protein interactions (PPIs), and the navigation from “undruggable” to a host of candidate molecules in clinical trials has been well-charted in recent, comprehensive reviews. Structure-based design has played an important role in this scientific journey, with three dimensional structures guiding medicinal chemistry efforts. However, the importance of two additional dimensions: movement and time is only now being realised, as increasing computing power, closely aligned with wet lab validation, is applied to the challenge. Protein dynamics are fundamental to biology and disease, and application to PPI drug discovery has massively widened the scope for new chemical entities to influence function from allosteric, and previously unreported, sites. In this forward-looking perspective we highlight exciting, new opportunities for small molecules to modulate disease biology, by adjusting the frequency profile of natural conformational sampling, through the stabilisation of clinically desired conformers of target proteins.
Pesticides and Soil Invertebrates: A Hazard Assessment
Authors: Gunstone Tari , Cornelisse Tara , Klein Kendra , Dubey Aditi , Donley Nathan
Published: May 2021

Agricultural pesticide use and its associated environmental harms is widespread throughout much of the world. Efforts to mitigate this harm have largely been focused on reducing pesticide contamination of the water and air, as runoff and pesticide drift are the most significant sources of offsite pesticide movement. Yet pesticide contamination of the soil can also result in environmental harm. Pesticides are often applied directly to soil as drenches and granules and increasingly in the form of seed coatings, making it important to understand how pesticides impact soil ecosystems. Soils contain an abundance of biologically diverse organisms that perform many important functions such as nutrient cycling, soil structure maintenance, carbon transformation, and the regulation of pests and diseases. Many terrestrial invertebrates have declined in recent decades. Habitat loss and agrichemical pollution due to agricultural intensification have been identified as major driving factors. Here, we review nearly 400 studies on the effects of pesticides on non-target invertebrates that have egg, larval, or immature development in the soil. This review encompasses 275 unique species, taxa or combined taxa of soil organisms and 284 different pesticide active ingredients or unique mixtures of active ingredients. We identified and extracted relevant data in relation to the following endpoints: mortality, abundance, biomass, behavior, reproduction, biochemical biomarkers, growth, richness and diversity, and structural changes. This resulted in an analysis of over 2,800 separate “tested parameters,” measured as a change in a specific endpoint following exposure of a specific organism to a specific pesticide. We found that 70.5% of tested parameters showed negative effects, whereas 1.4% and 28.1% of tested parameters showed positive or no significant effects from pesticide exposure, respectively. In addition, we discuss general effect trends among pesticide classes, taxa, and endpoints, as well as data gaps. Our review indicates that pesticides of all types pose a clear hazard to soil invertebrates. Negative effects are evident in both lab and field studies, across all studied pesticide classes, and in a wide variety of soil organisms and endpoints. The prevalence of negative effects in our results underscores the need for soil organisms to be represented in any risk analysis of a pesticide that has the potential to contaminate soil, and for any significant risk to be mitigated in a way that will specifically reduce harm to soil organisms and to the many important ecosystem services they provide.
A Study of the Regulatory Mechanism of the CB1/PPARγ2/PLIN1/HSL Pathway for Fat Metabolism in Cattle
Authors: Liu Ruili , Liu Xianxun , Bai Xuejin , Xiao Chaozhu , Dong Yajuan
Published: May 2021

Fat metabolism is closely related to the economic characteristics of beef cattle. Therefore, regulating fat deposition and increasing intramuscular fat deposition are among the main goals of breeders. In this study, we aim to explore the regulatory role of CB1 gene on PPARγ2/PLIN1/HSL pathway in fat metabolism, and to further explore the differential expression of regulatory factors of this pathway in Shandong black cattle and Luxi cattle. In this study, CB1 overexpression stimulated lipid synthesis in adipocytes to some extent by increasing the levels of FASN and ACSL1. CB1 inhibitors reduce the lipid content in adipocytes and reduce the expression of GLUT1 and Insig1. In addition, overexpression of CB1 decreased the expression of PPARγ2 and led to an increase in PLIN1 expression and a decrease in HSL expression in adipocytes. We also found that the CB1/PPARγ2/PLIN1/HSL was differentially expressed in the different breeds of cattle and was involved in the regulation of fat metabolism, which affected the fatty acid content in the longissimus dorsi muscle of the two breeds. In short, CB1 participates in lipid metabolism by regulating HSL in the PPARγ2 and PLIN1 pathways, and improves lipid formation in adipocytes. In conclusion, CB1/PPARγ2/PLIN1/HSL pathway may be involved in the regulation of lipid metabolism.
Comparison of Two Strategies to Generate Antigen-Specific Human Monoclonal Antibodies: Which Method to Choose for Which Purpose?
Authors: Ehlers Anna M. , den Hartog Jager Constance F. , Kardol-Hoefnagel Tineke , Katsburg Miriam M.D. , Knulst André C. , Otten Henny G.
Published: May 2021

Human monoclonal antibodies (mAbs) are valuable tools to link genetic information with functional features and to provide a platform for conformational epitope mapping. Additionally, combined data on genetic and functional features provide a valuable mosaic for systems immunology approaches. Strategies to generate human mAbs from peripheral blood have been described and used in several studies including single cell sequencing of antigen-binding B cells and the establishment of antigen-specific monoclonal Epstein-Barr Virus (EBV) immortalized lymphoblastoid cell lines (LCLs). However, direct comparisons of these two strategies are scarce. Hence, we sought to set up these two strategies in our laboratory using peanut 2S albumins (allergens) and the autoantigen anti-Rho guanosine diphosphate dissociation inhibitor 2 (RhoGDI2, alternatively ‘ARHGDIB’) as antigen targets to directly compare these strategies regarding costs, time expenditure, recovery, throughput and complexity. Regarding single cell sequencing, up to 50% of corresponding V(D)J gene transcripts were successfully amplified of which 54% were successfully cloned into expression vectors used for heterologous expression. Seventy-five percent of heterologously expressed mAbs showed specific binding to peanut 2S albumins resulting in an overall recovery of 20.3%, which may be increased to around 29% by ordering gene sequences commercially for antibody cloning. In comparison, the establishment of monoclonal EBV-LCLs showed a lower overall recovery of around 17.6%. Heterologous expression of a mAb carrying the same variable region as its native counterpart showed comparable concentration-dependent binding abilities. By directly comparing those two strategies, single cell sequencing allows a broad examination of antigen-binding mAbs in a moderate-throughput manner, while the establishment of monoclonal EBV-LCLs is a powerful tool to select a small number of highly reactive mAbs restricted to certain B cell subpopulations. Overall, both strategies, initially set-up for peanut 2S albumins, are suitable to obtain human mAbs and they are easily transferrable to other target antigens as shown for ARHGDIB.
argoFloats: An R Package for Analyzing Argo Data
Authors: Kelley Dan E. , Harbin Jaimie , Richards Clark
Published: May 2021

An R package named argoFloats has been developed to facilitate identifying, downloading, caching, and analyzing oceanographic data collected by Argo profiling floats. The analysis phase benefits from close connections between argoFloats and the oce package, which is likely to be familiar to those who already use R for the analysis of oceanographic data of other kinds. This paper outlines how to use argoFloats to accomplish some everyday tasks that are particular to Argo data, ranging from downloading data and finding subsets to handling quality control and producing a variety of diagnostic plots. The benefits of the R environment are sketched in the examples, and also in some notes on the future of the argoFloats package.
On the Influence of Microtopography on the Sliding Performance of Cross Country Skis
Authors: Scherge Matthias , Stoll Melissa , Moseler Michael
Published: May 2021

The sliding performance of cross country skis is mainly influenced by the ability of the ski base to minimize capillary forces and contact area. Whereas, the first condition depends on hydrophobicity, the second one is controlled by the ski grinding structure and the morphology of snow. In this contribution the results of sliding tests with five typical grinding structures will be presented and compared to calculations of the real area of contact. Surface topographies were measured and corresponding roughness features were analyzed by 3D optical microscopy. The measured ski base profiles and the measured grain size distribution of granular snow at −2°C were employed within a bearing model for a rough surface in contact with loose and freely-moving snow grains treated as ice spheres. For the five grinding structures, this model revealed a good correlation of the real area of contact between ski and snow with run times in lab-condition sliding tests. The results indicate that the snow-containing volume of the grinding structure is pivotal for tailoring the sliding behavior.
Post-COVID-19 Syndrome: The Persistent Symptoms at the Post-viral Stage of the Disease. A Systematic Review of the Current Data
Authors: Salamanna Francesca , Veronesi Francesca , Martini Lucia , Landini Maria Paola , Fini Milena
Published: May 2021

Whilst the entire world is battling the second wave of COVID-19, a substantial proportion of patients who have suffered from the condition in the past months are reporting symptoms that last for months after recovery, i. e., long-term COVID-19 symptoms. We aimed to assess the current evidence on the long-term symptoms in COVID-19 patients. We did a systematic review on PubMed, Web of Science, EMBASE, and Google Scholar from database inception to February 15, 2021, for studies on long-term COVID-19 symptoms. We included all type of papers that reported at least one long-term COVID-19 symptom. We screened studies using a standardized data collection form and pooled data from published studies. Cohort cross-sectional, case-report, cases-series, case-control studies, and review were graded using specific quality assessment tools. Of 11,361 publications found following our initial search we assessed 218 full-text articles, of which 145 met all selection criteria. We found that 20.70% of reports on long-term COVID-19 symptoms were on abnormal lung functions, 24.13% on neurologic complaints and olfactory dysfunctions, and 55.17% on specific widespread symptoms, mainly chronic fatigue, and pain. Despite the relatively high heterogeneity of the reviewed studies, our findings highlighted that a noteworthy proportion of patients who have suffered from SARS-CoV-2 infection present a “post-COVID syndrome.” The multifaceted understanding of all aspects of the COVID-19 pandemic, including these long-term symptoms, will allow us to respond to all the global health challenges, thus paving the way to a stronger public health.
RNase J1 and J2 Are Host-Encoded Factors for Plasmid Replication
Authors: Guimarães Vanessa Andrade , Le Scornet Alexandre , Khemici Vanessa , Hausmann Stéphane , Armitano Joshua , Prados Julien , Jousselin Ambre , Manzano Caroline , Linder Patrick , Redder Peter
Published: May 2021

Plasmids need to ensure their transmission to both daughter-cells when their host divides, but should at the same time avoid overtaxing their hosts by directing excessive host-resources toward production of plasmid factors. Naturally occurring plasmids have therefore evolved regulatory mechanisms to restrict their copy-number in response to the volume of the cytoplasm. In many plasmid families, copy-number control is mediated by a small plasmid-specified RNA, which is continuously produced and rapidly degraded, to ensure that its concentration is proportional to the current plasmid copy-number. We show here that pSA564 from the RepA_N-family is regulated by a small antisense RNA (RNA1), which, when over-expressed in trans, blocks plasmid replication and cures the bacterial host. The 5′ untranslated region (5′UTR) of the plasmid replication initiation gene (repA) potentially forms two mutually exclusive secondary structures, ON and OFF, where the latter both sequesters the repA ribosome binding site and acts as a rho-independent transcriptional terminator. Duplex formation between RNA1 and the 5′UTR shifts the equilibrium to favor the putative OFF-structure, enabling a single small RNA to down-regulate repA expression at both transcriptional and translational levels. We further examine which sequence elements on the antisense RNA and on its 5′UTR target are needed for this regulation. Finally, we identify the host-encoded exoribonucleases RNase J1 and J2 as the enzymes responsible for rapidly degrading the replication-inhibiting section of RNA1. This region accumulates and blocks RepA expression in the absence of either RNase J1 or J2, which are therefore essential host factors for pSA564 replication in Staphylococcus aureus.
Cognition and Cerebrovascular Reactivity in Midlife Women With History of Preeclampsia and Placental Evidence of Maternal Vascular Malperfusion
Authors: Shaaban C. Elizabeth , Rosano Caterina , Cohen Ann D. , Huppert Theodore , Butters Meryl A. , Hengenius James , Parks W. Tony , Catov Janet M.
Published: May 2021

Background: Preeclampsia is emerging as a sex-specific risk factor for cerebral small vessel disease (SVD) and dementia, but the reason is unknown. We assessed the relationship of maternal vascular malperfusion (MVM), a marker of placental SVD, with cognition and cerebral SVD in women with and without preeclampsia. We hypothesized women with both preeclampsia and MVM would perform worst on information processing speed and executive function.

Methods: Women (n = 45; mean 10.5 years post-delivery; mean age: 41 years; 42.2% Black) were classified as preeclampsia-/MVM-, preeclampsia+/MVM-, or preeclampsia+/MVM+. Information processing speed, executive function, and memory were assessed. In a pilot sub-study of cerebrovascular reactivity (CVR; n = 22), cerebral blood flow during room-air breathing and breath-hold induced hypercapnia were obtained via arterial spin labeling MRI. Non-parametric tests and regression models were used to test associations.

Results: Between-group cognitive differences were significant for information processing speed (p = 0.02); preeclampsia+/MVM+ had the lowest scores. Cerebral blood flow increased from room-air to breath-hold, globally and in all regions in the three groups, except the preeclampsia+/MVM+ parietal region (p = 0.12). Lower parietal CVR (less change from room-air breathing to breath-holding) was correlated with poorer information processing speed (partial ρ = 0.63, p = 0.005) and executive function (ρ = 0.50, p = 0.03) independent of preeclampsia/MVM status.

Conclusion: Compared to women without preeclampsia and MVM, midlife women with both preeclampsia and MVM have worse information processing speed and may have blunted parietal CVR, an area important for information processing speed and executive function. MVM in women with preeclampsia is a promising sex-specific indicator of cerebrovascular integrity in midlife.
The Significance of Vascular Pathogenesis in the Examination of Corticobasal Syndrome
Authors: Dunalska Anna , Pikul Julia , Schok Katarzyna , Wiejak Katarzyna Anna , Alster Piotr
Published: May 2021

Corticobasal syndrome (CBS) is a clinical entity, classified as an atypical Parkinsonism, characterized by both motor and higher cortical dysfunctions. The clinical manifestation of CBS is associated with several pathologies, among which corticobasal degeneration (CBD) is the most common. The aim of our study was to elaborate on the possible vascular pathogenesis of CBS and consider types of vascular lesions in these cases. Several cases of vascular CBS are described in the literature. The majority of presented patients were affected by internal carotid artery (ICA) stenosis and ischemic strokes; few cases were associated with vascular malformations or autoimmune diseases. Vascular CBS is preceded by an abrupt onset. The clinical manifestation does not significantly differ with non-vascular CBS. Patients with vascular CBS are usually elderly; often with coexistent hypertension, dyslipidemia and diabetes mellitus. Inferring from our observations, cerebral hypoperfusion can play a significant role in neuropathological changes in neurodegenerative diseases. To the best of our knowledge paper is the first comprehensive review of vascular CBS and we are positive that our observations show that further research concerning the vascular pathogenesis of tauopathy atypical Parkinsonism is required.
Neuronal Glycoprotein M6a: An Emerging Molecule in Chemical Synapse Formation and Dysfunction
Authors: León Antonella , Aparicio Gabriela I. , Scorticati Camila
Published: May 2021

The cellular and molecular mechanisms underlying neuropsychiatric and neurodevelopmental disorders show that most of them can be categorized as synaptopathies—or damage of synaptic function and plasticity. Synaptic formation and maintenance are orchestrated by protein complexes that are in turn regulated in space and time during neuronal development allowing synaptic plasticity. However, the exact mechanisms by which these processes are managed remain unknown. Large-scale genomic and proteomic projects led to the discovery of new molecules and their associated variants as disease risk factors. Neuronal glycoprotein M6a, encoded by theGPM6Agene is emerging as one of these molecules. M6a has been involved in neuron development and synapse formation and plasticity, and was also recently proposed as a gene-target in various neuropsychiatric disorders where it could also be used as a biomarker. In this review, we provide an overview of the structure and molecular mechanisms by which glycoprotein M6a participates in synapse formation and maintenance. We also review evidence collected from patients carrying mutations in theGPM6Agene; animal models, andin vitrostudies that together emphasize the relevance of M6a, particularly in synapses and in neurological conditions.
The Effect of Vitamin D Supplementation on Clinical Outcomes for Critically Ill Patients: A Systemic Review and Meta-Analysis of Randomized Clinical Trials
Authors: Shen Hejuan , Mei Yijun , Zhang Kai , Xu Xiaoya
Published: May 2021

Purpose: Vitamin D deficiency is a common scenario in critically ill patients and has been proven to be associated with poor outcomes. However, the effect of vitamin D supplementation for critically ill patients remains controversial. Thus, we conducted a meta-analysis to evaluate the effect of vitamin D supplementation among critically ill patients.

Methods: Electronic databases PubMed, Embase, Scopus, and the Cochrane Library were searched for eligible randomized controlled trials between 2000 and January 2021. The primary outcome was overall mortality, and the secondary ones were the length of intensive care unit stay, the length of hospital stay, as well as the duration of mechanical ventilation. Subgroup analyses were performed to explore the treatment effect by type of admission, route of administration, dose of supplemented vitamin D, and the degree of vitamin D deficiency.

Results: A total of 14 studies involving 2,324 patients were finally included. No effect on overall mortality was found between vitamin D supplementation and control group [odds ratio (OR), 0.73; 95% CI, 0.52–1.03; I2 = 28%]. The vitamin D supplementation reduced the length of intensive care unit stay [mean difference (MD), −2.25; 95% CI, −4.07 to −0.44, I2 = 71%] and duration of mechanical ventilation (MD, −3.47; 95% CI, −6.37 to −0.57, I2 = 88%). In the subgroup analyses, the vitamin D supplementation for surgical patients (OR, 0.67; 95% CI, 0.47–0.94; I2 = 0%) or through parenteral way (OR, 0.42; 95% CI, 0.22–0.82, I2 = 0%) was associated with reduced mortality.

Conclusion: In critically ill patients, the supplementation of vitamin D has no effect on overall mortality compared to placebo but may decrease the length of intensive care unit stay and mechanical ventilation. Further trials are necessary to confirm our findings.
Epigenetic Silencing of Immune-Checkpoint Receptors in Bone Marrow- Infiltrating T Cells in Acute Myeloid Leukemia
Authors: Radpour Ramin , Stucki Miriam , Riether Carsten , Ochsenbein Adrian F.
Published: May 2021

Background

Immune-checkpoint (IC) inhibitors have revolutionized the treatment of multiple solid tumors and defined lymphomas, but they are largely ineffective in acute myeloid leukemia (AML). The reason why especially PD1/PD-L1 blocking agents are not efficacious is not well-understood but it may be due to the contribution of different IC ligand/receptor interactions that determine the function of T cells in AML.

Methods

To analyze the interactions of IC ligands and receptors in AML, we performed a comprehensive transcriptomic analysis of FACS-purified leukemia stem/progenitor cells and paired bone marrow (BM)-infiltrating CD4+ and CD8+ T cells from 30 patients with AML. The gene expression profiles of activating and inhibiting IC ligands and receptors were correlated with the clinical data. Epigenetic mechanisms were studied by inhibiting the histone deacetylase with valproic acid or by gene silencing of PAC1.

Results

We observed that IC ligands and receptors were mainly upregulated in leukemia stem cells. The gene expression of activating IC ligands and receptors correlated with improved prognosis and vice versa. In contrast, the majority of IC receptor genes were downregulated in BM-infiltrating CD8+ T cells and partially in CD4+ T cells, due to pathological chromatin remodeling via histone deacetylation. Therefore, treatment with histone deacetylase inhibitor (HDACi) or silencing of PAC1, as a T cell-specific epigenetic modulator, significantly increased the expression of IC receptors and defined effector molecules in CD8+ T cells.

Conclusions

Our results suggest that CD8+ T cells in AML are dysfunctional mainly due to pathological epigenetic silencing of activating IC receptors rather than due to signaling by immune inhibitory IC receptors, which may explain the limited efficacy of antibodies that block immune-inhibitory ICs in AML.
Sweat Testing and Recent Advances
Authors: Gokdemir Yasemin , Karadag Bulent Taner
Published: May 2021

Cystic fibrosis (CF) is the most common fatal genetic disease of the Caucasian population. Sweat testing is the principal diagnostic test for CF, and it is used for the evaluation of infants with positive CF newborn screening (NBS) and in patients with clinical findings suggesting CF. This article describes the classical sweat test method in detail and also provides an overwiew of recent advances.
Mortality and Outcomes of Pediatric Tracheostomy Dependent Patients
Authors: Hebbar Kiran B. , Kasi Ajay S. , Vielkind Monica , McCracken Courtney E. , Ivie Caroline C. , Prickett Kara K. , Simon Dawn M.
Published: May 2021

Objective: To describe clinical factors associated with mortality and causes of death in tracheostomy-dependent (TD) children.

Methods: A retrospective study of patients with a new or established tracheostomy requiring hospitalization at a large tertiary children's hospital between 2009 and 2015 was conducted. Patient groups were developed based on indication for tracheostomy: pulmonary, anatomic/airway obstruction, and neurologic causes. The outcome measures were overall mortality rate, mortality risk factors, and causes of death.

Results: A total of 187 patients were identified as TD with complete data available for 164 patients. Primary indications for tracheostomy included pulmonary (40%), anatomic/airway obstruction (36%), and neurologic (24%). The median age at tracheostomy and duration of follow up were 6.6 months (IQR 3.5–19.5 months) and 23.8 months (IQR 9.9–46.7 months), respectively. Overall, 45 (27%) patients died during the study period and the median time to death following tracheostomy was 9.8 months (IQR 6.1–29.7 months). Overall survival at 1- and 5-years following tracheostomy was 83% (95% CI: 76–88%) and 68% (95% CI: 57–76%), respectively. There was no significant difference in mortality based on indication for tracheostomy (p = 0.35), however pulmonary indication for tracheostomy was associated with a shorter time to death (HR: 1.9; 95% CI: 1.04–3.4; p = 0.04). Among the co-morbid medical conditions, children with seizure disorder had higher mortality (p = 0.04).

Conclusion: In this study, TD children had a high mortality rate with no significant difference in mortality based on indication for tracheostomy. Pulmonary indication for tracheostomy was associated with a shorter time to death and neurologic indication was associated with lower decannulation rates.
Integrated Random Negative Sampling and Uncertainty Sampling in Active Learning Improve Clinical Drug Safety Drug–Drug Interaction Information Retrieval
Authors: Xie Weixin , Wang Limei , Cheng Qi , Wang Xueying , Wang Ying , Bi Hongyuan , He Bo , Feng Weixing
Published: May 2021

Clinical drug–drug interactions (DDIs) have been a major cause for not only medical error but also adverse drug events (ADEs). The published literature on DDI clinical toxicity continues to grow significantly, and high-performance DDI information retrieval (IR) text mining methods are in high demand. The effectiveness of IR and its machine learning (ML) algorithm depends on the availability of a large amount of training and validation data that have been manually reviewed and annotated. In this study, we investigated how active learning (AL) might improve ML performance in clinical safety DDI IR analysis. We recognized that a direct application of AL would not address several primary challenges in DDI IR from the literature. For instance, the vast majority of abstracts in PubMed will be negative, existing positive and negative labeled samples do not represent the general sample distributions, and potentially biased samples may arise during uncertainty sampling in an AL algorithm. Therefore, we developed several novel sampling and ML schemes to improve AL performance in DDI IR analysis. In particular, random negative sampling was added as a part of AL since it has no expanse in the manual data label. We also used two ML algorithms in an AL process to differentiate random negative samples from manually labeled negative samples, and updated both the training and validation samples during the AL process to avoid or reduce biased sampling. Two supervised ML algorithms, support vector machine (SVM) and logistic regression (LR), were used to investigate the consistency of our proposed AL algorithm. Because the ultimate goal of clinical safety DDI IR is to retrieve all DDI toxicity–relevant abstracts, a recall rate of 0.99 was set in developing the AL methods. When we used our newly proposed AL method with SVM, the precision in differentiating the positive samples from manually labeled negative samples improved from 0.45 in the first round to 0.83 in the second round, and the precision in differentiating the positive samples from random negative samples improved from 0.70 to 0.82 in the first and second rounds, respectively. When our proposed AL method was used with LR, the improvements in precision followed a similar trend. However, the other AL algorithms tested did not show improved precision largely because of biased samples caused by the uncertainty sampling or differences between training and validation data sets.