bluuebunny/crossref_metadata_2025 huggingface dataset:
Contrast of positively charged oxide precipitate in out-lens, in-lens and in-column SE image
Authors: Mikmeková Šárka , Nakamichi Haruo , Nagoshi Masayasu
Published: December 2020

Modern scanning electron microscopes are usually equipped with multiple detectors and enable simultaneous collection of two or even three secondary electron images. The secondary electrons become divided between the detectors in dependence on their initial kinetic energy and emission angle. In this study, sharing of the secondary electrons by out-lens, in-lens and in-column detectors has been systematically investigated. Energy filtering of the signal electrons is demonstrated by separation of the voltage and the topographical contrast in the micrographs obtained by out-lens and in-lens/in-column detectors. The presence of two detectors inside the electron column enables further filtering of the low kinetic energy secondary electrons, which results to unusual contrasts and phenomena. In this paper, inversion of the contrast sign between a positively charged oxide particle and conductive steel matrix (i.e. voltage contrast) in SE images collected under specific imaging conditions is demonstrated.
Information Choice, Uncertainty, and Expected Returns
Authors: Cao Charles , Gempesaw David , Simin Timothy T
Published: December 2020

We investigate how information choices affect equity returns and risk. Building on an existing theoretical model of information and investment choice, we estimate a learning index that reflects the expected benefits of learning about an asset. High learning index stocks have lower future returns and risk compared to low learning index stocks. Analysis of a conditional asset pricing model, long-run patterns in returns and volatilities, other measures of information flow, and the information environment surrounding earnings announcements reinforce our interpretation of the learning index. Our findings support the model’s predictions and illustrate a novel empirical measure of investor learning.
Childhood B-Cell Acute Lymphoblastic Leukemia Following SARS CoV-2 Infection: A Potential Second “Hit” in Leukemogenesis
Authors: Persaud Yogindra , Shamoun Mark , Chitlur Meera , Des Rosier Kyle J. , Taub Jeffrey W.
Published: December 2020

The Coronavirus Disease 2019 (COVID-19) pandemic has become the worst pandemic in modern history. The lack of prior immunity to the virus has resulted in a high mortality rate, though children have fared better than adults, overall. We present a case of a child who developed B-cell acute lymphoblastic leukemia 1 week following a symptomatic COVID-19 infection. It is possible that this viral infection provided the “second hit” posited to occur in pediatric leukemogenesis as proposed by Dr Greaves, with his initial viral exposure occurring several weeks earlier.
Signaling interaction link prediction using deep graph neural networks integrating protein-protein interactions and omics data
Authors: Feng Jiarui , Zeng Amanda , Chen Yixin , Payne Philip , Li Fuhai
Published: December 2020

Uncovering signaling links or cascades among proteins that potentially regulate tumor development and drug response is one of the most critical and challenging tasks in cancer molecular biology. Inhibition of the targets on the core signaling cascades can be effective as novel cancer treatment regimens. However, signaling cascades inference remains an open problem, and there is a lack of effective computational models. The widely used gene co-expression network (no-direct signaling cascades) and shortest-path based protein-protein interaction (PPI) network analysis (with too many interactions, and did not consider the sparsity of signaling cascades) were not specifically designed to predict the direct and sparse signaling cascades. To resolve the challenges, we proposed a novel deep learning model,deepSignalingLinkNet, to predict signaling cascades by integrating transcriptomics data and copy number data of a large set of cancer samples with the protein-protein interactions (PPIs) via a novel deep graph neural network model. Different from the existing models, the proposed deep learning model was trained using the curated KEGG signaling pathways to identify the informative omics and PPI topology features in the data-driven manner to predict the potential signaling cascades. The validation results indicated the feasibility of signaling cascade prediction using the proposed deep learning models. Moreover, the trained model can potentially predict the signaling cascades among the new proteins by transferring the learned patterns on the curated signaling pathways. The code was available at:https://github.com/fuhaililab/deepSignalingPathwayPrediction.
An efficient lentiviral CRISPRi approach to silence genes in primary human monocytes
Authors: Liu Bingxu , Gentili Matteo , Lieb David , Eisenhaure Thomas , Irvine Darrell J. , Hacohen Nir
Published: December 2020

Human primary monocytes are critical in controlling immune responses and tissue homeostasis. However, to identify and study molecular components that underlie the function of these cells, there remains a need to develop methods to perturb genes in these cells. Here we report lentiviral-based delivery of dCas9-KRAB and guide RNAs to efficiently silent target genes, such asCD45andCD209. We further show that sgRNAs againstTICAM1dampen proinflammatory cytokine and interferon expression in response to lipopolysaccharide. When delivered by lentivirus, sgRNAs are incorporated into the genome, thus enabling pooled screening to perturb and identify coding and non-coding elements that contribute to the functions of primary human monocytes.
Red-beet betalain pigments inhibit amyloid-β aggregation and toxicity in amyloid-β expressingCaenorhabditis elegans
Authors: Imamura Tomohiro , Koga Hironori , Higashimura Yasuki , Isozumi Noriyoshi , Matsumoto Kenji , Ohki Shinya , Mori Masashi
Published: December 2020

BACKGROUND

Betalain pigments are mainly produced by plants in the order Caryophyllales. Recent interest in the biological functions of betalain pigments has increased with antioxidant, anti-inflammatory, and anticancer activities reported.

RESULTS

We investigated the effects of betalain pigments derived from red-beet on amyloid-β (Aβ) aggregation, a cause of Alzheimer’s disease. Inhibition of Aβ aggregation against Aβ40 and Aβ42 by betalain pigmentsin vitrowas demonstrated by the Thioflavin T fluorescence assay, circular dichroism spectroscopy analysis and transmission electron microscopic observations. Moreover, we examined the ability of betalain pigments to interfere with Aβ toxicity by using the transgenicCaenorhabditis elegansstrain CL2006, which expresses the human Aβ42 protein intracellularly within the body wall muscle and responds to Aβ-toxicity with paralysis. Treatment with 50 μM betalain pigments significantly delayed the paralysis ofCaenorhabditis elegans.

CONCLUSION

These results suggest that betalain pigments reduce Aβ-induced toxicity by inhibiting Aβ aggregation and may lead to their use as inhibitors of Aβ aggregation.
A new Dicistrovirus from soldier flyInopus flavus(James) (Diptera: Stratiomyidae), a pest of sugarcane
Authors: Asselin Angelique K. , Etabari Kayvan , Furlong Michael J. , Johnson Karyn N.
Published: December 2020

The native Australian soldier flies,Inopusspp. (Diptera: Stratiomyidae), are agricultural pests of economic importance to the sugarcane industry. While adult soldier flies do not feed on sugarcane, larvae spend one to two-years underground feeding on roots, causing mechanical and systemic damage to crops (Saccharum officinarum L.) that impacts yield. Current measures of pest control commonly target above ground pests and are ineffective against solider fly larvae, highlighting the importance of novel control methods. A screen of the salivary gland transcriptome ofInopus flavus(James) revealed the presence of viral RNA belonging to a potentially novel member of theDicistroviridaefamily. Viruses from this family have been found naturally infecting insects from a range of taxonomic groups and they often cause pathogenesis in their hosts. To characterise the genetic and physical properties of the new virus, the positive RNA genome was analysed using a combination of sequencing approaches. The virus genome is organised similarly to members of theDicistroviridaewith two open reading frames (ORF) the first encoding non-structural proteins and the second encoding structural proteins. The genome includes two potential internal ribosomal entry sites (IRES) one within the 5’ UTR and the other in the intergenic region (IGR). Based on the amino acid sequences of the non-structural and structural polyproteins encoded by the two ORF soldier fly virus groups within the dicistrovirus family. Virus particles purified from infected larvae and visualised by electron microscopy are icosahedral, non-enveloped, and 30 nm in diameter. The genetic and physical characteristics of this novel soldier fly virus are consistent with it being a member of theDicistroviridae.
Sustained antibody response to ZIKV infection induced by NS1 protein is accompanied by the progressive appearance of autoreactive antibodies and cross-reactive B cell clones
Authors: Cavazzoni Cecilia B. , Bozza Vicente B. T. , Tostes Lucas , Maia Bruno , Mesin Luka , Schiepers Ariën , Ersching Jonatan , Neris Romulo L.S. , Conde Jonas N. , Coelho Diego R. , Conde Luciana , de Paula Neto Heitor A. , Lima Tulio M. , Alvim Renata G.F. , Castilho Leda R. , Mohana-Borges Ronaldo , Assunção-Miranda Iranaia , Nobrega Alberto , Victora Gabriel D. , Vale Andre M.
Published: December 2020

Besides antigen-specific responses to viral antigens, humoral immune response in virus infection can generate polyreactive and autoreactive antibodies. Dengue and Zika virus infections have been linked to antibody-mediated autoimmune disorders including Guillain-Barrè syndrome. A unique feature of flaviviruses is the secretion of non-structural protein 1 (NS1) by infected cells. NS1 is highly immunogenic and antibodies targeting NS1 can have both protective and pathogenic roles. In the present study, we investigated the humoral immune response to Zika virus NS1 and found NS1 to be an immunodominant viral antigen associated with the presence of autoreactive antibodies. Through single B cell cultures, we coupled binding assays and BCR sequencing, confirming the immunodominance of NS1. Of note, we demonstrate the presence of self-reactive clones in germinal centers after both infection and immunization, some of which clones presenting cross-reactivity with NS1. Sequence analysis of anti-NS1 B cell clones showed sequence features associated with pathogenic autoreactive antibodies. Our findings demonstrate NS1 immunodominance at the cellular level as well as a potential role for NS1 in ZIKV associated autoimmune manifestations.
Experimental SARS-CoV-2 infection of bank voles - general susceptibility but lack of direct transmission
Authors: Ulrich Lorenz , Michelitsch Anna , Halwe Nico , Wernike Kerstin , Hoffmann Donata , Beer Martin
Published: December 2020

After experimental inoculation, SARS-CoV-2 infection was proven for bank voles by seroconversion within eight days and detection of viral RNA in nasal tissue for up to 21 days. However, transmission to contact animals was not detected. Therefore, bank voles are unlikely to establish effective SARS-CoV-2 transmission cycles in nature.

Article Summary Line

Bank voles show low-level viral replication and seroconversion upon infection with SARS-CoV-2, but lack transmission to contact animals.
MG53 is not a critical regulator of insulin signaling pathway in skeletal muscle
Authors: Philouze Clothilde , Turban Sophie , Cremers Béatrice , Caliez Audrey , Lamarche Gwladys , Bernard Catherine , Provost Nicolas , Delerive Philippe
Published: December 2020

In type 2 diabetes (T2D), both muscle and liver are severely resistant to insulin action. Muscle insulin resistance accounts for more than 80% of the impairment in total body glucose disposal in T2D patients and is often characterized by an impaired insulin signaling. Mitsugumin 53 (MG53), a muscle-specific TRIM family protein initially identified as a key regulator of cell membrane repair machinery has been suggested to be a critical regulator of muscle insulin signaling pathway by acting as ubiquitin E3 ligase targeting both the insulin receptor and insulin receptor substrate 1 (IRS1). Here, we show usingin vitroandin vivoapproaches that MG53 is not a critical regulator of insulin signaling and glucose homeostasis. First, MG53 expression is not consistently regulated in skeletal muscle from various preclinical models of insulin resistance. Second, MG53 gene knock-down in muscle cells does not lead to impaired insulin response as measured by Akt phosphorylation on Serine 473 and glucose uptake. Third, recombinant human MG53 does not alter insulin response in both differentiated C2C12 and human skeletal muscle cells. Fourth, ectopic expression of MG53 in HEK293 cells lacking endogenous MG53 expression fails to alter insulin response as measured by Akt phosphorylation. Finally, both male and female mg53 −/− mice were not resistant to high fat induced obesity and glucose intolerance compared to wild-type mice. Taken together, these results strongly suggest that MG53 is not a critical regulator of insulin signaling pathway in skeletal muscle.
Retrospective analysis of the use of osteoporosis medication at the presentation of fragility fractures in a predominantly Hispanic population
Authors: Serra-Torres Michael J. , Torres-Reveron Annelyn
Published: December 2020

Despite the high incidence of osteoporosis, many patients at risk of fragility fractures may not initiate treatment due to concerns about side effects, or cost. We aimed to identify whether the patient population presenting with fragility fractures is receiving prophylactic treatment for osteoporosis within a single academic hospital in the southernmost region of the United States. This region is characterized by a high number of patients from Hispanic/Latino heritage (80%) and reduced access to healthcare services. We conducted a three-year, retrospective cohort study of patients presenting with low impact fractures of the humerus or the shoulder griddle, lower end of radius or ulna and forearm, hip fractures (femoral neck, intertrochanteric/subtrochanteric), the lower end of tibia, medial malleolus, lateral malleolus or lower leg. Male and female subjects of 50 years or older were included. Demographic data and information on medications reported at fracture presentation were extracted from electronic medical records. We found that 42% of the patients were taking at least one medication to prevent osteoporosis. The predominant combination was vitamin D plus calcium and bisphosphonates. If patients taking only vitamin D plus calcium are excluded, 16.7% of the sample took osteoporosis medications at the fragility fracture presentation. The likelihood of taking osteoporosis medication was increased by age and type of health insurance (Medicare/private insurance), and concomitant diagnosis of impaired gait and mobility. The percentage of the patients taking prophylactic medications for osteoporosis at the time of a fragility fracture was comparable to reported national standards and associated with increased age and health insurance coverage. In a predominantly Hispanic/Latino patient population living in a medically underserved region, there is substantial recognition and prevention strategies for osteoporosis.
Cytoplasmic and nuclear Sw-5b NLR act both independently and synergistically to dictate full host defense against tospovirus infection
Authors: Chen Hongyu , Qian Xin , Chen Xiaojiao , Yang Tongqing , Feng Mingfeng , Chen Jing , Cheng Ruixiang , Hong Hao , Zheng Ying , Mei Yuzhen , Shen Danyu , Xu Yi , Zhu Min , Ding Xin Shun , Tao Xiaorong
Published: December 2020

Plant intracellular nucleotide binding-leucine-rich repeat (NLR) receptors play critical roles in mediating host immunity to pathogen attack. We use tomato Sw-5b::tospovirus as a model system to study the specific role of the compartmentalized plant NLR in dictating host defense against virus at different infection steps.

We demonstrated here that tomato NLR Sw-5b translocates to cytoplasm and nucleus, respectively, to play different roles in inducing host resistances againstTomato spotted wilt tospovirus(TSWV) infection. The cytoplasmic Sw-5b functions to induce a strong cell death response to inhibit TSWV replication. This host response is, however, insufficient to block viral intercellular and long-distance movement. The nucleus-localized Sw-5b triggers a host defense that weakly inhibits viral replication but strongly impedes virus intercellular and systemic movement. Furthermore, the cytoplasmic and nuclear Sw-5b act synergistically to dictate full host defense to TSWV infection.

We further demonstrated that the extended N-terminalSolanaceaedomain (SD) of Sw-5b plays critical roles in cytoplasm/nucleus partitioning. Sw-5b nucleotide-binding leucine-rich repeat (NB-LRR) controls its cytoplasm localization. Strikingly, the SD but not coil-coil (CC) domain is crucial for Sw-5b receptor to translocate from cytoplasm to nucleus to trigger the immunity. The SD was found to interact with importins. Silencing both importin α and β expression disrupted Sw-5b nucleus translocation and host immunity against TSWV systemic infection.

Collectively, our findings suggest that Sw-5b bifurcates disease resistances by cytoplasm/nucleus partitioning to block different infection steps of TSWV. The findings also identified a new regulatory role of extra domain of a plant NLR in mediating host innate immunity.
Development of a continuous fluorescence-based assay for N-terminal acetyltransferase D
Authors: Ho Yi-Hsun , Chen Lan , Huang Rong
Published: December 2020

N-terminal acetylation catalyzed by N-terminal acetyltransferases (NATs) has various biological functions in protein regulation. N-terminal acetyltransferase D (NatD) is one of the most specific NAT with only histone H4 and H2A proteins as the known substrates. Dysregulation of NatD has been implicated in colorectal and lung cancer progression, implying its therapeutic potential in cancers. However, there is no reported inhibitor for NatD yet. To facilitate the discovery of small-molecule NatD inhibitors, we report the development of a fluorescence-based acetyltransferase assay in 384-well high-throughput screening (HTS) format through monitoring the formation of coenzyme A. The fluorescent signal is generated from the adduct in the reaction between coenzyme A and fluorescent probe ThioGlo4. The assay exhibited a Z’-factor of 0.77 and a coefficient of variation of 6%, indicating it is a robust assay for HTS. A pilot screen of 1280 pharmacologically active compounds and subsequent validation identified two hits, confirming the application of this fluorescence assay in HTS.
Retracing the evolutionary trajectory of adenine base editors using theoretical approaches
Authors: Rallapalli Kartik L. , Ranzau Brodie L. , Ganapathy Kaushik R. , Komor Alexis C. , Paesani Francesco
Published: December 2020

Adenine base editors (ABEs) have been subjected to multiple rounds of mutagenesis with the goal of optimizing their function as efficient and precise genome editing agents. Despite this ever-increasing data accumulation of the effects that these mutations have on the activity of ABEs, the molecular mechanisms defining these changes in activity remain to be elucidated. In this study, we provide a systematic interpretation of the nature of these mutations using an entropy-based classification model that relies on evolutionary data from extant protein sequences. Using this model in conjunction with experimental analyses, we identify two previously reported mutations that form an epistatic pair in the RNA-editing functional landscape of ABEs. Molecular dynamics simulations reveal the atomistic details of how these two mutations affect substrate-binding and catalytic activity, via both individual and cooperative effects, hence providing insights into the mechanisms through which these two mutations are epistatically coupled.
Risk-related decision making evokes distinct brain activation patterns in reward evaluation regions in substance use naïve versus non-naïve adolescents
Authors: McQuaid Goldie A. , Darcey Valerie L. , Patterson Amanda E. , Rose Emma J. , VanMeter John W. , Fishbein Diana H.
Published: December 2020

Identifying brain and behavioral precursors to substance use (SU) may guide interventions that delay initiation in youth at risk for SU disorders (SUD). Heightened reward-sensitivity and risk-taking may confer risk for SUD. In a longitudinal, prospective study, we characterized behavioral and neural profiles associated with reward-sensitivity and risk-taking in substance-naïve adolescents, examining whether they differed as a function of SU initiation at 18- and 36-months follow-up.

Adolescents (N=70; 11.1-14.0 years) completed a reward-related decision-making task (Wheel of Fortune (WOF)) while undergoing functional MRI. Measures of reward sensitivity (Behavioral Inhibition System-Behavioral Approach System; BIS-BAS), impulsive decision-making (delay discounting task), and SUD risk (Drug Use Screening Inventory, Revised (DUSI-R)) were collected at baseline. Baseline metrics were compared for youth who did (SI;n=27) and did not (SN;n=43) initiate SU at follow-up.

While groups displayed similar discounting and risk taking behavior, SI youth showed more variable patterns of activation in left insular cortex during high-risk selections, and left anterior cingulate cortex in response to rewarded outcomes. SI participants scored higher on the DUSI-R and BAS subscales. Results suggest differences in brain regions critical in the development and experience of SUDs may precede SU and serve as a biomarker for SUD risk.
Associative memory networks for graph-based abstraction
Authors: Haga Tatsuya , Fukai Tomoki
Published: December 2020

Our cognition relies on the ability of the brain to segment hierarchically structured events on multiple scales. Recent evidence suggests that the brain performs this event segmentation based on the structure of state-transition graphs behind sequential experiences. However, the underlying circuit mechanisms are only poorly understood. In this paper, we propose an extended attractor network model for the graph-based hierarchical computation, called as Laplacian associative memory. This model generates multiscale representations for communities (clusters) of associative links between memory items, and the scale is regulated by heterogenous modulation of inhibitory circuits. We analytically and numerically show that these representations correspond to graph Laplacian eigenvectors, a popular method for graph segmentation and dimensionality reduction. Finally, we demonstrate that our model with asymmetricity exhibits chunking resembling to hippocampal theta sequences. Our model connects graph theory and the attractor dynamics to provide a biologically plausible mechanism for abstraction in the brain.
Measurement error models reveal the scale of consumer movements along an isoscape gradient
Authors: Rodríguez Marco A.
Published: December 2020

In isotopic studies of mobile consumers, measurement error in spatial location is almost inevitable when individuals are observed only once. This error can have considerable impacts on the interpretation of ecologically important features, such as individual movement behaviour and dietary niche breadth. This study introduces a measurement error modelling framework for estimating movement scale and isotopic fractionation for consumers that move and feed along a linear isoscape gradient.

The model assumes that the key mechanism underlying the difference in spatial isotopic regression slopes of mobile consumers and their baseline resources is the presence of measurement error in the spatial location of consumers. Measurement error is assumed to arise from consumer movements, which are represented by realistic movement kernels. Simulations with known parameter values are used to evaluate the performance of the models under scenarios involving different combinations of consumer mobility and sample size. Several variants of the model are fit to empirical data, and their parameter estimates are compared with those of alternative models.

In simulations with known parameter values, model estimates of movement scale converged to the known values and had substantially smaller bias and variance than those of alternative models. Estimates of movement scale and fractionation for empirical data were consistent with previously reported estimates.

Neglecting measurement error in spatial location is likely to hinder progress in spatial isotopic analyses. The proposed framework provides a statistically principled basis for incorporating measurement error in spatial location into isoscape analyses to provide improved estimates of parameters of interest, such as movement scale and fractionation. The framework is sufficiently general to be applicable to a variety of species, isotopic tracers, environments and spatial scales. Logical next steps to extend the framework could involve modelling of multiple species, nonlinear isoscape gradients and 2‐dimensional isoscapes.
Vitamin D3–elicited CD14+ human skin dendritic cells promote thymic stromal lymphopoietin–independent type 2 T‐helper responses
Authors: Brulefert Adrien , Hoste Astrid , Muller Quentin , Fauny Jean‐Daniel , Mueller Christopher G. , Flacher Vincent
Published: December 2020

Background

Immune modulation by vitamin D3 through dendritic cells (DCs) remains controversial. Human DCs exposed in vitro counteract type‐1 T‐helper (Th1) differentiation and induce regulatory T cells. However, cutaneous application on mice promotes Th2‐driven inflammation resembling atopic dermatitis and relying on thymic stromal lymphopoietin (TSLP) from keratinocytes and T‐cell orientation by TSLP‐stimulated skin DCs. We studied the effects of vitamin D3 in human skin, focusing on TSLP production and the role of skin DCs in T‐cell differentiation.

Methods

Human healthy skin explants were exposed in vitro to vitamin D3 analogs. Migrating DCs were analyzed and TSLP quantified in the supernatant. Allogeneic naïve CD4+ T cells were cocultured with DCs to assess their proliferation and cytokine production.

Results

Vitamin D3 induced skin DCs to differentiate Th2 cells producing IL‐4 and IL‐13. Vitamin D3 triggered TSLP release in ~30% of skin explants, correlating with IL‐13 detection in Th2 cells. In these donors, blocking TSLP receptor during skin explant cultures abrogated IL‐13 production, yet IL‐4+ Th2 cells were unaffected. Among skin DCs emerged CD14+ cells that had responded directly to vitamin D3 and differed from classical CD14+ dermal emigrants. Vitamin D3‐elicited CD14+ DCs sufficed to promote IL‐4+ Th2 cells in a TSLP‐independent manner.

Conclusion

Vitamin D3, despite inducing TSLP in some donors, had a direct influence on skin DCs, affecting their phenotype and ability to drive Th2 responses independently of TSLP. Our findings pave the way toward in vitro systems that accurately model human cutaneous Th2 responses, notably involved in atopic dermatitis.
SGLT2 inhibitors and GLP1 agonists administered without metformin compared to other glucose‐lowering drugs in patients with type 2 diabetes mellitus to prevent cardiovascular events: A systematic review
Authors: Escobar Carlos , Barrios Vivencio , Cosín Juan , Gámez Martínez José María , Huelmos Rodrigo Ana Isabel , Ortíz Cortés Carolina , Torres Llergo Javier , Requeijo Carolina , Solà Ivan , Martínez Zapata Mª José
Published: December 2020

Objectives

To assess the efficacy of glucagon‐like peptide‐1 receptor agonists (GLP1‐RAs) and sodium‐glucose co‐transporter 2 (SGLT2) inhibitors, administered without metformin on cardiovascular outcomes in type 2 diabetes patients.

Methods

A systematic review was performed according to Cochrane's methodological standards. We included randomized clinical trials (RCTs) on adult type 2 diabetes patients, assessing the efficacy of SGLT2 inhibitors and GLP1‐RAs compared to other glucose‐lowering drugs and/or RCTs that presented data of a subgroup of type 2 diabetes patients without metformin use at baseline. The main outcome was the reduction of the risk of any major adverse cardiovascular events (MACE) reported individually or as a composite outcome.

Results

Five RCTs including 50,725 type 2 diabetes patients, of whom 10,013 had not received metformin, were included in this meta‐analysis. Three of these studies assessed the efficacy of GLP1‐RAs and two of SGLT2 inhibitors. In patients without metformin at baseline, GLP1‐RAs in comparison with placebo reduced the risk of MACE significantly by 20% (HR: 0.80; 95% CI: 0.71–0.89). SGLT2 inhibitors also significantly reduced the risk of MACE by 32% (HR: 0.68; 95% CI: 0.57–0.81).

Conclusions

SGLT2 inhibitors and GLP1‐RAs provided without metformin at baseline may reduce the risk of MACE in comparison with placebo in type 2 diabetes patients at increased risk of cardiovascular events.
The psychopathology of recurrent diabetic ketoacidosis: A case–control study
Authors: Garrett Christopher J. , Moulton Calum D. , Choudhary Pratik , Amiel Stephanie A. , Fonagy Peter , Ismail Khalida
Published: December 2020

Background

Despite its poor prognosis, the psychological factors associated with recurrent diabetic ketoacidosis are poorly understood. In people with type 1 diabetes, we assessed for psychopathology in those with and without recurrent diabetic ketoacidosis (DKA).

Method

The design was a case–control study. Cases were defined as people with two or more DKA episodes in a 12‐month period (recurrent DKA). Cases and controls were matched for gender and age. We compared groups for scores on Beck's Anxiety Inventory (BAI), Beck's Depression Inventory II, Difficulty in Emotion Regulation Scale (DERS), Experiences in Close Relationships‐Revised, Standardised Assessment of Personality‐Abbreviated Scale (SAPAS), Interpersonal Problem Inventory, Eating Disorder Examination Questionnaire and Problem Areas in Diabetes (PAID) using unpaired t‐tests or Mann–Whitney U tests for parametric and non‐parametric data, respectively. Correction was made for multiple testing.

Results

In all, 23 cases and 23 controls were recruited with mean age 31.0 (11.4) years and 65.2% were men. Cases had higher HbA1c levels than controls (101.1 (23.2) vs. 85.7 (21.7) mmol/mol, (p = 0.02)). Compared to controls, people with recurrent DKA had higher scores on the BAI (p = 0.004), PAID (p = 0.004), DERS (p = 0.001) and SAPAS (p < 0.001). Sixteen of 23 (69.6%) cases screened positive for a personality disorder compared to 6 of 23 (26.1%) controls.

Conclusions

People with recurrent DKA have elevated levels of anxiety and diabetes distress, greater difficulty with emotion regulation and personality dysfunction compared to matched controls.
Making it “Easy to Help”: The Evolution of Norwegian Volunteer Initiatives for Refugees
Authors: Jumbert Maria Gabrielsen
Published: December 2020

At the height of the refugee reception crisis in 2015, a large number of volunteers across Norway mobilized to bring assistance in different forms. The two most notable initiatives were Refugees Welcome Norway (RWN) and A Drop in the Ocean (Dråpen i Havet, DiH). RWN focused on those arriving in Norway and DiH on those arriving in Greece. Looking at these two initiatives’ organizational trajectories together allows us to examine how they managed the transition from the immediate ‘crisis’ and large volunteer mobilization to finding a role for themselves in the longer‐term. Drawing on social movement theory and literature on humanitarian action, the article argues that the two organizations, while adapting in different ways, focused their organizations around ‘making it easy’ for volunteers to help. The article explores how this allowed to forge their distinct identity in the organizational landscape, while also engaging with volunteers’ ‘need to do something’.
A comparison of avoidance to acoustic stimuli in fish with different auditory capabilities: juvenile chum salmon (Oncorhynchus keta) and common carp (Cyprinus carpio)
Authors: Matsuda Keishi
Published: December 2020

This study compared the repulsive effects of sound playbacks of intermittent 30, 150, 300, 600 and 900 Hz tones on two fish with different auditory capabilities: juvenile chum salmon (Oncorhynchus keta) and common carp (Cyprinus carpio). When 150 and 300 Hz tones were emitted from an underwater speaker, O. keta exhibited a moderate repulse reaction. Conversely, C. carpio exhibited a moderate repulse reaction to a tone with a frequency of 30 Hz, which indicates that a low‐frequency component in complex broadband sound may be important for inducing a repulse reaction in cyprinids.
End‐of‐Life Cost Trajectories in Cancer Patients Treated by Medicare versus the Veterans Health Administration
Authors: Gidwani Risha , Asch Steven M. , Needleman Jack , Faricy‐Anderson Katherine , Boothroyd Derek B. , Illarmo Samantha , Lorenz Karl A. , Patel Manali I. , Hsin Gary , Ramchandran Kavitha , Wagner Todd H.
Published: December 2020

BACKGROUND/OBJECTIVES

To evaluate differences in end‐of‐life cost trajectories for cancer patients treated through Medicare versus by the Veterans Health Administration (VA).

DESIGN

A retrospective analysis of VA and Medicare administrative data from FY 2010 to 2014. We employed three‐level generalized estimating equations to evaluate monthly cost trajectories experienced by patients in their last year of life, with patients nested within hospital referral region.

SETTING

Care received at VA facilities or by Medicare‐reimbursed providers nationwide.

PARTICIPANTS

A total of 36,401 patients dying from cancer and dually enrolled in VA and Medicare.

MEASUREMENTS

We evaluated trajectories for total, inpatient, outpatient, and drug costs, using the last 12 months of life. Cost trajectories were prioritized as costs are not directly comparable across Medicare and VA. Patients were assigned to be VA‐reliant, Medicare‐reliant or Mixed‐reliant based on their healthcare utilization in the last year of life.

RESULTS

All three groups experienced significantly different cost trajectories for total costs in the last year of life. Inpatient cost trajectories were significantly different between Medicare‐reliant and VA‐reliant patients, but did not differ between VA‐reliant and Mixed‐reliant patients. Outpatient and drug cost trajectories exhibited the inverse pattern: they were significantly different between VA‐reliant and Mixed‐reliant patients, but not between VA‐reliant and Medicare‐reliant patients. However, visual examination of cost trajectories revealed similar cost patterns in the last year of life among all three groups; there was a sharp rise in costs as patients approach death, largely due to inpatient care.

CONCLUSION

Despite substantially different financial incentives and organization, VA‐ and Medicare‐treated patients exhibit similar patterns of increasing end‐of‐life costs, largely driven by inpatient costs. Both systems require improvement to ensure quality of end‐of‐life care is aligned with recommended practice.
The discovery of the HLA‐B*56:75 allele shows that HLA sequencing is important in all transplant settings
Authors: Quon Justin C. , Lyle William D. , Baxter‐Lowe Lee Ann
Published: December 2020

HLA‐B*56:75 has a nonsynonymous C to G substitution in codon 73 compared to HLA‐B*56:01:01:02.
Defining postoperative transfusion thresholds in liver transplant recipients: A novel retrospective approach
Authors: Connor Joseph P. , Aufhauser David , Welch Bridget M. , Leverson Glen , Al‐Adra David
Published: December 2020

Background

The optimal transfusion threshold for most patient populations has been defined as hematocrit (HCT) <21%. However, some specific patient populations are known to benefit from higher transfusion thresholds. To date, the optimal postoperative transfusion threshold for patients undergoing liver transplant has not been determined. To define the ideal transfusion threshold for liver transplant patients, we designed a retrospective study of 496 liver transplant recipients.

Methods

Using HCT prior to discharge as a surrogate marker for transfusion thresholds we grouped patients into three groups of transfusion thresholds (HCT <21%, <24%, and >30%). Transfusion rates (intra‐ and postoperative), graft and patient survival, and complications requiring readmission were compared between groups.

Results

Ninety‐two percent of patients were transfused during their hospital stay. Graft survival, patient survival, and rates of readmission within 30 days of discharge were no different between the three discharge HCT groups. Patients discharged with HCT >30% were less likely to be readmitted with infectious complications; however, this group also had the lowest model of end‐stage liver (MELD) score at time of transplantation and were less likely to have received a transfusion during their hospital stay.

Conclusion

Transfusion thresholds of HCT <24%, and potentially as low as 21% are acceptable in postoperative liver transplant recipients. The conduct of a randomized clinical trial, as supported by these data, will be necessary to support the use of lower thresholds.
Assessing Level of Knowledge and Uptake of Hepatitis B Vaccination among Health Care Workers at Juba Teaching Hospital, Juba City, South Sudan
Authors: Alege John Bosco , Gulom Godfrey , Ochom Alphonse , Kaku Viola Emmanuel
Published: December 2020

Background. Chronic hepatitis B (CHB) virus (HBV) infection remains a severe problem worldwide. An estimated 240–400 million persons are reported to have chronic HBV infection, and the annual mortality from HBV-related complications including cirrhosis and hepatocellular carcinoma was 600,000 persons. In Sub-Saharan Africa, the prevalence of HBV chronic infection is particularly high while in South Sudan, hepatitis B remains a serious problem of public health importance with health care workers being more at greater risk. Vaccination coverage against HBV is low among all age groups, yet vaccination status among health care workers is not even known in South Sudan. This study aimed at assessing viral hepatitis B vaccination uptake among health care workers at Juba Teaching Hospital, Juba City, South Sudan. Objective. To assess the uptake of viral hepatitis B vaccination among health care workers in Juba Teaching Hospital, Juba City, South Sudan. Methods. An analytical cross-sectional study design was conducted targeting 154 health workers. A convenient sampling procedure was used to recruit study participants. Questionnaires were used to collect data. SPSS version 20.0 was used for data analysis. Chi-square tests were used to determine the association between the uptake of hepatitis B vaccination and individual and health facility factors. Multivariable analysis was conducted. Adjusted OR was used to interpret the findings. Results. Uptake of hepatitis B vaccination was found to be low at 44.20%, only 48.8% had received one dose, 29.1% received two doses, and 22.1% had received all three doses. Being married (

p
≤
0.008

), knowing that hepatitis B can be prevented by vaccination (

p
≤
0.001

), knowing that HBV can be got through unprotected sexual intercourse (

p
≤
0.001

), awareness of where to get hepatitis B vaccination from (

p
≤
0.001

), availability of vaccines in the health facility (

p
≤
0.027

), and availability of guidelines followed by all health workers in this facility (

p
≤
0.006

) were the factors independently associated with the uptake of hepatitis B vaccination. Conclusion. The uptake of hepatitis B vaccination among health workers at Juba Teaching Hospital was low (22.1%), putting health workers at great risk of HBV infection. Having knowledge about hepatitis B vaccination and unprotected sexual intercourse were individual factors associated with hepatitis B vaccination. Availability of the vaccine and vaccination guidelines were the health-related factors associated with hepatitis B vaccination. The government of South Sudan through the Ministry of Health should first track approval of the viral hepatitis B vaccination policy and ensure that it is adopted and implemented by all hospitals. Health care workers must be prioritized and mandatorily vaccinated against viral hepatitis B.
Have a Korean Lineage and Transmit a Chinese One Too: Lineage Practices in Seon Buddhism
Authors: Ahn Juhn Y.
Published: December 2020

Today, Korean dharma lineages all trace themselves back to Seosan Hyujeong 西山休靜 (1520–1604). Although some claim that Hyujeong’s own lineage should be traced back to Taego Bou 太古普愚 (1301–1382), others claim that it should be traced back to Naong Hyegeun 懶翁慧勤 (1320–1376) instead. The present article will demonstrate that both claims are flawed. They fail to take an important fact into account: the assumptions that guided lineage practices in the fourteenth century were no longer guiding lineage practices in the seventeenth century, which is when both claims were first made. Attempts to trace Hyujeong’s lineage to either Taego or Naong mistakenly accept the veracity of seventeenth-century lineage claims and assumptions. In pre-seventeenth century Korea Seon masters who received dharma transmission in China officially recognized not only their Chinese Chan lineage but also their Korean Seon lineage(s). As shown in this article, there was nothing wrong with having two or more dharma lineages in Korea. Hyegeun is a good example. He claimed to have inherited two different dharma lineages and may have even had a third. Hyegeun’s lineage began to lose favor, this article argues, because it did not accord with the new assumptions that began to guide lineage practices in seventeenth-century Korea.
Experimental and Theoretical Nuclear Magnetic Resonance Data from Tryptanthrin, an Alkaloid with Potential Activity Against Human Coronavirus
Authors: Costa Fabio Luiz Paranhos , Fernandes Sidnei Bessa de Oliveira , Fingolo Catharina Eccard , Boylan Fabio , Neto Antônio M. de J. Chaves , Mota Gunar Vingre da Silva , Soares Breno Almeida , Siqueira Marcelo Ricardo Souza , Giacomello Thaís Forest
Published: December 2020

Coronaviruses belong to the subfamily Coronavirinae, which are large viruses with a single Ribonucleic acid tape and a nucleocapsid. In a recent study it was found that the molecule of tryptanthrin has antiviral potential against human coronavirus NL63. In this work, we used
a combination of theoretical techniques with experimental nuclear magnetic resonance data to assist in the structural characterization of the Tryptanthrin molecule. Tryptanthrin was extracted from Couroupita guianensis leaves. The theoretical calculations of hydrogen-1, homonuclear
spin–spin coupling constants and the quantum theory of atoms in molecules were performed employing density functional theory. Our results show that the hydrogen-1 chemical shifts calculated at the gaseous phase and solvent presented similar performance. The quantum theory of atoms in
molecules calculations was able to quantify and qualify bonded interactions based on five topological parameters obtained at the analyzed bond critical point to tryptanthrin molecule. We obtained a satisfactory correlation between tryptanthrin delocalization index values and its experimental
and calculated proton–proton coupling constants. In conclusion, the theoretical techniques used in this work in combination with NMR experimental data can be a useful tool in aiding the structural determination of organic compounds.
Biosynthesizing Gold Nanoparticles with Parkia biglobosa Leaf Extract for Antibacterial Efficacy In Vitro and Photocatalytic Degradation Activities of Rhodamine B Dye
Authors: Shine Davids Joan , Shasha Sun , Kingdom Alorku , Emmanuel Okoampah , Fometu Sandra Senyo , Guohua Wu
Published: December 2020

The toxicity and cost involved in the synthesis of nanoparticles using physical and chemical methods have led to the emergence of biological techniques being employed by scientists. Hence the present study employed an eco-friendly method by using Parkia biglobosa leaves extract
as a reducing and stabilizing agent of chloroauric gold (HAuCl4) to gold nanoparticle (AuNPs). Direct Analysis in Real-Time (DART-MS) was employed for phytochemical screening. However, the AuNPs were characterized by Ultraviolet-Visible spectroscopy (UV/Vis), Transmission Electron
Microscopy (TEM), Energy Dispersive X-ray spectroscopy, Fourier Transmission Infrared Spectroscopy, and X-ray diffraction spectroscopy, before the antibacterial and photocatalysis study. DART-MS showed more than 20 phytochemicals, including phenolic compounds. The FT-IR revealed the existence
of flavonoids that we hypothesized are responsible for gold chloride reduction reactions. The optical properties of the gold nanoparticles by UV/Vis spectra registered plasmon surface resonance at a peak of 530 nm, whiles TEM revealed the AuNPs to be mono-dispersed and shapes were spherical
and triangular with sizes ranging from 3.4 nm to 39.7 nm. XRD also recorded face-centered cubic AuNPs with 20.94 nm as the average crystallite size. The synthesized AuNPs were able to elucidate their anti-bacterial efficacy on Gram-positive bacteria Staphylococcus aureus, enterococcus faecalis
and Gram-negative bacteria Escherichia coli, pseudomonas aeruginosa. The photocatalytic activities of AuNPs under UV/Vis irradiation exhibited a substantial degradation effect on rhodamine b (RhB) within 75 minutes. Due to their non-toxic nature, plant-mediated biosynthesized AuNPs,
would be valuable in enhancing their biomedical applications and in wastewater treatment.
Joint Modeling of Longitudinal Measurements and Multiple Failure Time Using Fully-specified Subdistribution Model: A Bayesian Perspective
Authors: Hosseini-Baharanchi F. S. , Baghestani A. R. , Baghfalaki T. , Hajizadeh E. , Najafizadeh K. , Shafaghi S.
Published: December 2020

In biomedical studies, competing risks framework in which an individual fails due to multiple causes is frequently available. Joint modeling of longitudinal measurements and competing risks has become prominent, recently. In this paper, we proposed a joint model considering fully-specified subdistribution model introduced by Ge and Chen (2012) and longitudinal measurements. The proposed model links a linear mixed effect submodel to a fully-specified subdistribution submodel through a shared random effect. A Bayesian paradigm using MCMC is adopted to estimate the parameters. Performance of the proposed model is illustrated using a simulation study. In addition, this model is used to analyze the lung transplant dataset.
TEKSTİL SEKTÖRÜNDE SÜRDÜRÜLEBİLİRLİĞİN ANALİZİ: KAHRAMANMARAŞ’TA FAALİYET GÖSTEREN BİR TEKSTİL İŞLETMESİNDE DEMATEL UYGULAMASI
Authors: ERDEM Mehri Banu , DOĞAN Nuri Özgür
Published: December 2020

Sürdürülebilirlik, bugünün ihtiyaçlarını; gelecek nesillerin ihtiyaçlarına zarar vermeden karşılayabilmektir. İnsanoğlunun günümüzde ihtiyaçtan çok keyfi olarak tüketime yönelmesiyle birlikte tüketim hızı da giderek artmaktadır. Özellikle moda anlayışının da tekstil sektörüne getirmiş olduğu keyfi tüketim, bu sektörün ekosistemi bozan sektörler arasında önemli bir yer edinmesine neden olmuştur. Bu çalışmada, tekstil ve konfeksiyon sektöründe Türkiye’nin önde gelen illerinden biri olan Kahramanmaraş’ın sürdürülebilirlikte karşılaştığı zorlukların belirlenerek modellenmesi amaçlanmıştır. Araştırma 10 adet kriter belirlenerek yürütülmüştür. Çalışmada çok kriterli karar verme tekniklerinden DEMATEL yöntemi kullanılmış, veriler ilgili sektörden uzmanlarla yüz yüze görüşme yöntemiyle elde edilmiştir. Verilerin analizi sonucu elde edilen bulguların yorumlanması neticesinde genel olarak sistemde en baskın kriter karmaşık tedarik zincirleri olarak ortaya çıkmıştır. Sistem içerisindeki etkisi en az olan kriterin ise hükümet politikalarının eksikliği olduğu belirlenmiştir. Bu sonuçlardan yola çıkılarak Kahramanmaraş ilinin tekstil sektörünün sürdürülebilirlikteki mevcut durumunun iyileştirilmesine yönelik bir takım önerilerde bulunulmuştur.