bluuebunny/crossref_metadata_2025 huggingface dataset:
Narrowband diffuse reflectance spectroscopy in the 900–1000 nm wavelength region to quantify water and lipid content of turbid media
Authors: Lam Jesse H. , Tu Kelsey J. , Kim Sehwan
Published: April 2021

We report a narrow wavelength band diffuse reflectance spectroscopy (nb-DRS) method to determine water and fat ratios of scattering media in the 900–1000 nm range. This method was shown to be linearly correlated with absolute water and fat concentrations as tested on a set of turbid emulsion phantoms with a range of water and lipid compositions. Robustness to scattering assumptions was demonstrated and compared against measured scattering by a frequency-domain photon migration system. nb-DRS was also tested on ex-vivo porcine samples and compared against direct tissue water extraction by analytical chemistry methods. We speculate nb-DRS has potential applications in portable devices such as clinical and digital health wearables.
Direct generation of optical vortex arrays by rotating in an all-solid-state Yb:CALGO laser
Authors: Yuan Ye , Tong Luyang , Cai Fangxin , Zhang Wenyu , Cai Yangjian , Zhao Lina
Published: April 2021

We report the direct generation of optical vortex arrays in a diode-pumped bulk Yb:CALGO laser. By adjusting the angles of the input mirror, output coupler and laser crystal to achieve off-axis-pumped condition, the ring-shaped LG0,±1, two to six order vortex array have been obtained. The phase singularities of optical vortex arrays were tunable from 1 to 6. When the pump power was 13.41 W, the maximum output power of LG0,±1, double-vortex array, three-vortex array and four-vortex array were 1.93 W, 1.5 W, 1.02 W and 0.79 W respectively. The chirality could be adjusted by rotating the output coupler. The topological charges of each phase singularity were determined by interference pattern. Theoretical simulation including intensity distribution, interference fringes and phase distribution have been analyzed. The simulations are in good accordance with experimental results.
The mysterious ecosystem at the ocean’s surface
Authors: Helm Rebecca R.
Published: April 2021

Life on the ocean’s surface connects worlds. From shallow waters to the deep sea, the open ocean to rivers and lakes, numerous terrestrial and marine species depend on the surface ecosystem and the organisms found therein. Organisms that live freely at the surface, termed “neuston,” include keystone organisms like the golden seaweedSargassumthat makes up the Sargasso Sea, floating barnacles, snails, nudibranchs, and cnidarians. Many ecologically and economically important fish species live as or rely upon neuston. Species at the surface are not distributed uniformly; the ocean’s surface harbors unique neustonic communities and ecoregions found at only certain latitudes and only in specific ocean basins. But the surface is also on the front line of climate change and pollution. Despite the diversity and importance of the ocean’s surface in connecting disparate habitats, and the risks it faces, we know very little about neustonic life. This Essay will introduce you to the neuston, their connections to diverse habitats, the threats they face, and new opportunities for research and discovery at the air-sea interface.
ANGPTL8 protein-truncating variant associated with lower serum triglycerides and risk of coronary disease
Authors: Helkkula Pyry , Kiiskinen Tuomo , Havulinna Aki S. , Karjalainen Juha , Koskinen Seppo , Salomaa Veikko , Daly Mark J. , Palotie Aarno , Surakka Ida , Ripatti Samuli ,   FinnGen
Published: April 2021

Protein-truncating variants (PTVs) affecting dyslipidemia risk may point to therapeutic targets for cardiometabolic disease. Our objective was to identify PTVs that were associated with both lipid levels and the risk of coronary artery disease (CAD) or type 2 diabetes (T2D) and assess their possible associations with risks of other diseases. To achieve this aim, we leveraged the enrichment of PTVs in the Finnish population and tested the association of low-frequency PTVs in 1,209 genes with serum lipid levels in the Finrisk Study (n = 23,435). We then tested which of the lipid-associated PTVs were also associated with the risks of T2D or CAD, as well as 2,683 disease endpoints curated in the FinnGen Study (n = 218,792). Two PTVs were associated with both lipid levels and the risk of CAD or T2D: triglyceride-lowering variants in ANGPTL8 (-24.0[-30.4 to -16.9] mg/dL per rs760351239-T allele, P = 3.4 × 10−9) and ANGPTL4 (-14.4[-18.6 to -9.8] mg/dL per rs746226153-G allele, P = 4.3 × 10−9). The risk of T2D was lower in carriers of the ANGPTL4 PTV (OR = 0.70[0.60–0.81], P = 2.2 × 10−6) than noncarriers. The odds of CAD were 47% lower in carriers of a PTV in ANGPTL8 (OR = 0.53[0.37–0.76], P = 4.5 × 10−4) than noncarriers. Finally, the phenome-wide scan of the ANGPTL8 PTV showed that the ANGPTL8 PTV carriers were less likely to use statin therapy (68,782 cases, OR = 0.52[0.40–0.68], P = 1.7 × 10−6) compared to noncarriers. Our findings provide genetic evidence of potential long-term efficacy and safety of therapeutic targeting of dyslipidemias.
Basement membrane proteins as a substrate for efficient Trypanosoma brucei differentiation in vitro
Authors: Rojas Federico , Cayla Mathieu , Matthews Keith R.
Published: April 2021

The ability to reproduce the developmental events of trypanosomes that occur in their mammalian host in vitro offers significant potential to assist in understanding of the underlying biology of the process. For example, the transition from bloodstream slender to bloodstream stumpy forms is a quorum-sensing response to the parasite-derived peptidase digestion products of environmental proteins. As an abundant physiological substrate in vivo, we studied the ability of a basement membrane matrix enriched gel (BME) in the culture medium to support differentiation of pleomorphic Trypanosoma brucei to stumpy forms. BME comprises extracellular matrix proteins, which are among the most abundant proteins found in connective tissues in mammals and known substrates of parasite-released peptidases. We previously showed that two of these released peptidases are involved in generating a signal that promotes slender-to-stumpy differentiation. Here, we tested the ability of basement membrane extract to enhance parasite differentiation through its provision of suitable substrates to generate the quorum sensing signal, namely oligopeptides. Our results show that when grown in the presence of BME, T. brucei pleomorphic cells arrest at the G0/1 phase of the cell cycle and express the differentiation marker PAD1, the response being restricted to differentiation-competent parasites. Further, the stumpy forms generated in BME medium are able to efficiently proceed onto the next life cycle stage in vitro, procyclic forms, when incubated with cis-aconitate, further validating the in vitro BME differentiation system. Hence, BME provides a suitable in vitro substrate able to accurately recapitulate physiological parasite differentiation without the use of experimental animals.
The worldwide seroprevalence of DENV, CHIKV and ZIKV infection: A systematic review and meta-analysis
Authors: Li Zhihui , Wang Jin , Cheng Xiaomin , Hu Huan , Guo Cheng , Huang Jingyi , Chen Zeliang , Lu Jiahai
Published: April 2021

Background

As the three major arthropod-borne viruses, dengue virus (DENV), chikungunya virus (CHIKV), and zika virus (ZIKV) are posing a growing threat to global public health and socioeconomic development. Our study aimed to systematically review the global seroprevalences of these arboviruses from existing publications.

Methods

Articles published between Jan 01, 2000 and Dec 31, 2019 in the databases of Embase, Pubmed and Web of Science were searched and collected. Countries or areas with known local presence of Aedes vector mosquitoes were included. Random effects model was utilized to estimate the pooled seroprevalences and the proportion of inapparent infection.

Results

Out of 1375, a total of 133 articles involving 176,001 subjects were included for our analysis. The pooled seroprevalences of DENV, CHIKV and ZIKV were 38%, 25% and 18%, respectively; and their corresponding proportions of inapparent infections were 80%, 40% and 50%. The South-East Asia Region had the highest seroprevalences of DENV and CHIKV, while the Region of the Americas had the highest seroprevalence of ZIKV. The seroprevalences of DENV and CHIKV were similar when comparing developed and developing countries, urban and rural areas, or among different populations. In addition, we observed a decreased global seroprevalences in the new decade (2010–2019) comparing to the decade before (2000–2009) for CHIKV. For ZIKV, the positive rates tested with the nucleic acid detection method were lower than those tested with the antibody detection method. Lastly, numerous cases of dual seropositivity for CHIKV and DENV were reported.

Conclusions

Our results revealed a varied prevalence of arbovirus infections in different geographical regions and countries, and the inapparent infection accounted an unneglected portion of infections that requires more attention. This study will shed lights on our understanding of the true burden of arbovirus infections and promote appropriate vaccination in the future.
Identification of antigenic linear peptides in the soil-transmitted helminth and Schistosoma mansoni proteome
Authors: Vlaminck Johnny , Lagatie Ole , Dana Daniel , Mekonnen Zeleke , Geldhof Peter , Levecke Bruno , Stuyver Lieven J.
Published: April 2021

The scientific community identified non stool-based biomarkers as the way forward to support soil-transmitted helminth (STH; Ascaris lumbricoides, Trichuris trichiura and the hookworms Ancylostoma duodenale and Necator americanus) and schistosome (S. mansoni and S. haematobium) deworming programs. This support is needed in making the decision of whether or not to stop preventive chemotherapy intervention efforts and to ultimately transition towards a post-intervention surveillance phase. We applied a two-step micro-array approach to identify antigenic linear epitopes in the STH and S. mansoni proteomes. In a first experiment, we identified antigenic peptides by applying sera from 24 STH and/or S. mansoni infected Ethiopian children on a high-density peptide microarray containing 3.3 million peptides derived from the complete STH and S. mansoni proteomes. A second array experiment with 170,185 peptides that were recognized in the first array was designed to identify non-specific antibody reactivity by applying sera from 24 healthy individuals from Belgium (a non-endemic country). From this array testing cascade, several peptides were identified for STH but none of them appeared to be unique for one species. We therefore concluded that for STH, none of the peptides revealed to be sufficiently sensitive or species specific. For S. mansoni, some promising peptides were identified prompting future investigation. Based on these results, it is unlikely that linear epitopes would be highly useful in detecting species-specific antibody responses to STH in endemic communities. For S. mansoni, one particular peptide of the micro-exon gene 12 (MEG-12) protein deserves further research. In addition, this study emphasizes the need of well-characterized biobanks for biomarker discovery, particularly when the integration of multiple disease programs is envisioned.
Analytical validation and performance characteristics of a 48-gene next-generation sequencing panel for detecting potentially actionable genomic alterations in myeloid neoplasms
Authors: Rosenthal Sun Hee , Gerasimova Anna , Ma Charles , Li Hai-Rong , Grupe Andrew , Chong Hansook , Acab Allan , Smolgovsky Alla , Owen Renius , Elzinga Christopher , Chen Rebecca , Sugganth Daniel , Freitas Tracey , Graham Jennifer , Champion Kristen , Bhattacharya Anindya , Racke Frederick , Lacbawan Felicitas
Published: April 2021

Identification of genomic mutations by molecular testing plays an important role in diagnosis, prognosis, and treatment of myeloid neoplasms. Next-generation sequencing (NGS) is an efficient method for simultaneous detection of clinically significant genomic mutations with high sensitivity. Various NGS based in-house developed and commercial myeloid neoplasm panels have been integrated into routine clinical practice. However, some genes frequently mutated in myeloid malignancies are particularly difficult to sequence with NGS panels (e.g., CEBPA, CARL, and FLT3). We report development and validation of a 48-gene NGS panel that includes genes that are technically challenging for molecular profiling of myeloid neoplasms including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and myeloproliferative neoplasms (MPN). Target regions were captured by hybridization with complementary biotinylated DNA baits, and NGS was performed on an Illumina NextSeq500 instrument. A bioinformatics pipeline that was developed in-house was used to detect single nucleotide variations (SNVs), insertions/deletions (indels), and FLT3 internal tandem duplications (FLT3-ITD). An analytical validation study was performed on 184 unique specimens for variants with allele frequencies ≥5%. Variants identified by the 48-gene panel were compared to those identified by a 35-gene hematologic neoplasms panel using an additional 137 unique specimens. The developed assay was applied to a large cohort (n = 2,053) of patients with suspected myeloid neoplasms. Analytical validation yielded 99.6% sensitivity (95% CI: 98.9–99.9%) and 100% specificity (95% CI: 100%). Concordance of variants detected by the 2 tested panels was 100%. Among patients with suspected myeloid neoplasms (n = 2,053), 54.5% patients harbored at least one clinically significant mutation: 77% in AML patients, 48% in MDS, and 45% in MPN. Together, these findings demonstrate that the assay can identify mutations associated with diagnosis, prognosis, and treatment options of myeloid neoplasms even in technically challenging genes.
A pseudomolecule assembly of the Rocky Mountain elk genome
Authors: Masonbrink Rick E. , Alt David , Bayles Darrell O. , Boggiatto Paola , Edwards William , Tatum Fred , Williams Jeffrey , Wilson-Welder Jennifer , Zimin Aleksey , Severin Andrew , Olsen Steven
Published: April 2021

Rocky Mountain elk (Cervus canadensis) populations have significant economic implications to the cattle industry, as they are a major reservoir forBrucella abortusin the Greater Yellowstone area. Vaccination attempts against intracellular bacterial diseases in elk populations have not been successful due to a negligible adaptive cellular immune response. A lack of genomic resources has impeded attempts to better understand why vaccination does not induce protective immunity. To overcome this limitation, PacBio, Illumina, and Hi-C sequencing with a total of 686-fold coverage was used to assemble the elk genome into 35 pseudomolecules. A robust gene annotation was generated resulting in 18,013 gene models and 33,422 mRNAs. The accuracy of the assembly was assessed using synteny to the red deer and cattle genomes identifying several chromosomal rearrangements, fusions and fissions. Because this genome assembly and annotation provide a foundation for genome-enabled exploration of Cervus species, we demonstrate its utility by exploring the conservation of immune system-related genes. We conclude by comparing cattle immune system-related genes to the elk genome, revealing eight putative gene losses in elk.
Internal, external and repeated-sprint demands in small-sided games: A comparison between bouts and age groups in elite youth soccer players
Authors: Hauer Richard , Störchle Paul , Karsten Bettina , Tschan Harald , Baca Arnold
Published: April 2021

This study investigated the activity profile during small-sided games (SSG) in elite youth soccer players. Internal load (IL) including heart rate (HR) and external load (EL) such as distance covered in different speed-zones (SZ) were collected from forty-eight players of three different teams (U15, U16, U18). The investigation included a total of eighteen 5vs.5 SSGs, each consisting of four 2-minute bouts on a 40x32m pitch during spring season. Total group results (n = 48) showed a reduction in total-distance (p = 0.001; ηp2 = 0.12), high-intensity-running (p = 0.009; ηp2 = 0.09), and low-intensity-running distance (p = 0.028; ηp2 = 0.07) between bouts. Similarly, a reduction in the number of both acceleration-low (p = 0.001; ηp2 = 0.12) and deceleration-high (p = 0.003; ηp2 = 0.11) values was observed. Additionally, time spent in HR-zones 3 and 4 (p≤0.007; ηp2 ≥ 0.10), increased, with a reduction in HR-zone 1 (p = 0.000, ηp2 = 0.25). Age group comparison showed less distance covered in SZ 1 (p≤0.000; ηp2 = 0.56) and greater deceleration-high values (p≤0.038; ηp2 = 0.32) in U15 players compared to other age groups. Further, U15 showed lower values in low-intensity-running compared to U18 (p = 0.038; ηp2 = 0.22). No age-related differences were found for IL and repeated sprint ability (RSA) values. The higher EL in younger age groups should be taken into account when implementing soccer specific SSGs. In addition, HRmean values between 80–85% of HRmax and RSA numbers, which are similar to match-play data, indicate SSGs as an effective training tool to prepare youth soccer athletes for the demands of competition.
Iron can be microbially extracted from Lunar and Martian regolith simulants and 3D printed into tough structural materials
Authors: Castelein Sofie M. , Aarts Tom F. , Schleppi Juergen , Hendrikx Ruud , Böttger Amarante J. , Benz Dominik , Marechal Maude , Makaya Advenit , Brouns Stan J. J. , Schwentenwein Martin , Meyer Anne S. , Lehner Benjamin A. E.
Published: April 2021

In-situ resource utilization (ISRU) is increasingly acknowledged as an essential requirement for the construction of sustainable extra-terrestrial colonies. Even with decreasing launch costs, the ultimate goal of establishing colonies must be the usage of resources found at the destination of interest. Typical approaches towards ISRU are often constrained by the mass and energy requirements of transporting processing machineries, such as rovers and massive reactors, and the vast amount of consumables needed. Application of self-reproducing bacteria for the extraction of resources is a promising approach to reduce these pitfalls. In this work, the bacterium Shewanella oneidensis was used to reduce three different types of Lunar and Martian regolith simulants, allowing for the magnetic extraction of iron-rich materials. The combination of bacterial treatment and magnetic extraction resulted in a 5.8-times higher quantity of iron and 43.6% higher iron concentration compared to solely magnetic extraction. The materials were 3D printed into cylinders and the mechanical properties were tested, resulting in a 400% improvement in compressive strength in the bacterially treated samples. This work demonstrates a proof of concept for the on-demand production of construction and replacement parts in space exploration.
Changing parental feeding practices through web-based interventions: A systematic review and meta-analysis
Authors: Gomes Ana Isabel , Pereira Ana Isabel , Roberto Magda Sofia , Boraska Klara , Barros Luisa
Published: April 2021

Web-based parent interventions designed to promote children’s healthy eating patterns can enhance parents’ engagement and facilitate behavior change. However, it is still unclear how much the existing programs focus on changing parental feeding practices, and if so, which behavioral methodologies are used and how effective these interventions are in changing these parental behaviors. This systematic review and meta-analysis studied randomized controlled trials of web-based interventions targeting parents of 0-12-year-old children, aiming to promote children’s healthy diet or prevent nutrition-related problems and reporting parental feeding behaviors as one of the outcomes. We conducted an electronic search in four databases from the earliest publication date until February 2020. Of the 1271 records found, we retained twelve studies about nine programs, comprising 1766 parents that completed the baseline evaluation. We found recent interventions, mainly directed to parents of young children, with small, non-clinical samples, and mostly theory-based. The programs were heterogeneous regarding the type of intervention delivered and its duration. The most assessed parental feeding practices were Restriction, Pressure to eat, and Food availability/accessibility. The behavior change techniques Instruction on how to perform the behavior, Demonstration of the behavior, and Identification of self as role model were frequently used. Meta-analytic results indicated that most programs’ effects were small for the evaluated parental practices, except for Food availability/accessibility that benefited the intervention group only when all follow-up measurements were considered. The development of high-quality and controlled trials with larger samples is needed to determine with greater certainty the interventions’ impact on parental feeding behaviors. The more frequent inclusion of measures to evaluate parental practices to support children’s autonomy and of self-regulatory strategies as intervention components should be considered when designing programs.
Seroprevalence of anti-SARS-CoV-2 antibodies in a cohort of New York City metro blood donors using multiple SARS-CoV-2 serological assays: Implications for controlling the epidemic and “Reopening”
Authors: Jin Daniel K. , Nesbitt Daniel J. , Yang Jenny , Chen Haidee , Horowitz Julie , Jones Marcus , Vandergaast Rianna , Carey Timothy , Reiter Samantha , Russell Stephen J. , Kyratsous Christos , Hooper Andrea , Hamilton Jennifer , Ferreira Manuel , Deng Sarah , Straus Donna , Baras Aris , Hillyer Christopher D. , Luchsinger Larry L.
Published: April 2021

Projections of the stage of the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) pandemic and local, regional and national public health policies to limit coronavirus spread as well as “reopen” cities and states, are best informed by serum neutralizing antibody titers measured by reproducible, high throughput, and statically credible antibody (Ab) assays. To date, a myriad of Ab tests, both available and FDA authorized for emergency, has led to confusion rather than insight per se. The present study reports the results of a rapid, point-in-time 1,000-person cohort study using serial blood donors in the New York City metropolitan area (NYC) using multiple serological tests, including enzyme-linked immunosorbent assays (ELISAs) and high throughput serological assays (HTSAs). These were then tested and associated with assays for neutralizing Ab (NAb). Of the 1,000 NYC blood donor samples in late June and early July 2020, 12.1% and 10.9% were seropositive using the Ortho Total Ig and the Abbott IgG HTSA assays, respectively. These serological assays correlated with neutralization activity specific to SARS-CoV-2. The data reported herein suggest that seroconversion in this population occurred in approximately 1 in 8 blood donors from the beginning of the pandemic in NYC (considered March 1, 2020). These findings deviate with an earlier seroprevalence study in NYC showing 13.7% positivity. Collectively however, these data demonstrate that a low number of individuals have serologic evidence of infection during this “first wave” and suggest that the notion of “herd immunity” at rates of ~60% or higher are not near. Furthermore, the data presented herein show that the nature of the Ab-based immunity is not invariably associated with the development of NAb. While the blood donor population may not mimic precisely the NYC population as a whole, rapid assessment of seroprevalence in this cohort and serial reassessment could aid public health decision making.
Effect of focused ultrasound cavitation augmented with aerobic exercise on abdominal and intrahepatic fat in patients with non-alcoholic fatty liver disease: A randomized controlled trial
Authors: Taha Mona Mohamed , Aneis Yasser M. , Mohamady Heba Mohamed , S. A. Alrasheedy , Elsayed Shereen Hamed
Published: April 2021

Objectives

The study aimed to examine the effect of focused ultrasound cavitation augmented with aerobic exercise on localized abdominal and intrahepatic fat in fatty liver patients.

Methods

34 fatty liver patients aged 30–45 with a body mass index (BMI) of 30–40 kg/m2 were randomly assigned into two equally numbered groups. Group A received focused ultrasound cavitation and moderate aerobic exercise for three months, while Group B (control group) received moderate aerobic exercise only. Abdominal subcutaneous fat volume, visceral fat volume, liver-to-spleen ratio (L/S ratio), body weight, BMI, and waist circumference were measured both before and after the study period.

Results

Both groups showed significant improvements in subcutaneous fat volume, visceral fat volume, body weight, BMI, and waist circumference relative to baseline where (P < 0.001), with a higher percentage in group A. L/S ratio only showed a significant improvement in group A. Between-group differences were noteworthy regarding L/S ratio and waist circumference where (P < 0.0001).

Conclusion

While substantial risky measures in non-alcoholic fatty liver disease have been modified by aerobic exercise, its combination with focused ultrasound cavitation causes more notable effects on the reduction of abdominal and intrahepatic fat, making it a superior option.

Trial registration

ClinicalTrials.gov: NCT04161703
Particle jet impact deep-rock in rotary drilling: Failure process and lab experiment
Authors: Fang Tiancheng , Ren Fushen , Wang Baojin , Cheng Jianxun , Liu Hanxu
Published: April 2021

Aimed at the technical problems of low drilling speed and difficult rock-breaking in deep-well and hard rock-stratum, particle waterjet coupled impact rock-breaking technology in rotary drilling is put forward in this paper. Firstly, the working principle of particle jet impact rock-breaking in rotary drilling was introduced, and the acceleration model of particle jet and the damage model of rock were established. The acceleration mechanism of particles and dynamic damage evolution process of rock under particle jet were studied, which showed that the broken pit and rock damage would increase with time gone on, and damage evolution of rock presented the radial expansion. Then, experimental device of particle jet coupled impact rock-breaking in rotary state was developed, and the effect of jet parameters on penetration depth and failure volume was analyzed with comparison of la experiment and numerical simulation. The results showed that drilling speed with particle jet impact is twice that of conventional drilling, and combination nozzles layout of impact angle with 8°and 20° can achieve rock-drilled rapidly, which also demonstrated the correctness of simulation method. The device development and the rock-breaking results analysis would be of great value for engineering application.
Impact of environmental changes on the dynamics of temporal networks
Authors: Kim Hyewon , Jo Hang-Hyun , Jeong Hawoong
Published: April 2021

Dynamics of complex social systems has often been described in the framework of temporal networks, where links are considered to exist only at the moment of interaction between nodes. Such interaction patterns are not only driven by internal interaction mechanisms, but also affected by environmental changes. To investigate the impact of the environmental changes on the dynamics of temporal networks, we analyze several face-to-face interaction datasets using the multiscale entropy (MSE) method to find that the observed temporal correlations can be categorized according to the environmental similarity of datasets such as classes and break times in schools. By devising and studying a temporal network model considering a periodically changing environment as well as a preferential activation mechanism, we numerically show that our model could successfully reproduce various empirical results by the MSE method in terms of multiscale temporal correlations. Our results demonstrate that the environmental changes can play an important role in shaping the dynamics of temporal networks when the interactions between nodes are influenced by the environment of the systems.
Pathological findings in organs and tissues of patients with COVID-19: A systematic review
Authors: Peiris Sasha , Mesa Hector , Aysola Agnes , Manivel Juan , Toledo Joao , Borges-Sa Marcio , Aldighieri Sylvain , Reveiz Ludovic
Published: April 2021

Background

Coronavirus disease (COVID-19) is the pandemic caused by SARS-CoV-2 that has caused more than 2.2 million deaths worldwide. We summarize the reported pathologic findings on biopsy and autopsy in patients with severe/fatal COVID-19 and documented the presence and/or effect of SARS-CoV-2 in all organs.

Methods and findings

A systematic search of the PubMed, Embase, MedRxiv, Lilacs and Epistemonikos databases from January to August 2020 for all case reports and case series that reported histopathologic findings of COVID-19 infection at autopsy or tissue biopsy was performed. 603 COVID-19 cases from 75 of 451 screened studies met inclusion criteria. The most common pathologic findings were lungs: diffuse alveolar damage (DAD) (92%) and superimposed acute bronchopneumonia (27%); liver: hepatitis (21%), heart: myocarditis (11.4%). Vasculitis was common only in skin biopsies (25%). Microthrombi were described in the placenta (57.9%), lung (38%), kidney (20%), Central Nervous System (CNS) (18%), and gastrointestinal (GI) tract (2%). Injury of endothelial cells was common in the lung (18%) and heart (4%). Hemodynamic changes such as necrosis due to hypoxia/hypoperfusion, edema and congestion were common in kidney (53%), liver (48%), CNS (31%) and GI tract (18%). SARS-CoV-2 viral particles were demonstrated within organ-specific cells in the trachea, lung, liver, large intestine, kidney, CNS either by electron microscopy, immunofluorescence, or immunohistochemistry. Additional tissues were positive by Polymerase Chain Reaction (PCR) tests only. The included studies were from numerous countries, some were not peer reviewed, and some studies were performed by subspecialists, resulting in variable and inconsistent reporting or over statement of the reported findings.

Conclusions

The main pathologic findings of severe/fatal COVID-19 infection are DAD, changes related to coagulopathy and/or hemodynamic compromise. In addition, according to the observed organ damage myocarditis may be associated with sequelae.
Risk of rapid evolutionary escape from biomedical interventions targeting SARS-CoV-2 spike protein
Authors: Van Egeren Debra , Novokhodko Alexander , Stoddard Madison , Tran Uyen , Zetter Bruce , Rogers Michael , Pentelute Bradley L. , Carlson Jonathan M. , Hixon Mark , Joseph-McCarthy Diane , Chakravarty Arijit
Published: April 2021

The spike protein receptor-binding domain (RBD) of SARS-CoV-2 is the molecular target for many vaccines and antibody-based prophylactics aimed at bringing COVID-19 under control. Such a narrow molecular focus raises the specter of viral immune evasion as a potential failure mode for these biomedical interventions. With the emergence of new strains of SARS-CoV-2 with altered transmissibility and immune evasion potential, a critical question is this: how easily can the virus escape neutralizing antibodies (nAbs) targeting the spike RBD? To answer this question, we combined an analysis of the RBD structure-function with an evolutionary modeling framework. Our structure-function analysis revealed that epitopes for RBD-targeting nAbs overlap one another substantially and can be evaded by escape mutants with ACE2 affinities comparable to the wild type, that are observed in sequence surveillance data and infect cells in vitro. This suggests that the fitness cost of nAb-evading mutations is low. We then used evolutionary modeling to predict the frequency of immune escape before and after the widespread presence of nAbs due to vaccines, passive immunization or natural immunity. Our modeling suggests that SARS-CoV-2 mutants with one or two mildly deleterious mutations are expected to exist in high numbers due to neutral genetic variation, and consequently resistance to vaccines or other prophylactics that rely on one or two antibodies for protection can develop quickly -and repeatedly- under positive selection. Predicted resistance timelines are comparable to those of the decay kinetics of nAbs raised against vaccinal or natural antigens, raising a second potential mechanism for loss of immunity in the population. Strategies for viral elimination should therefore be diversified across molecular targets and therapeutic modalities.
Potential impact of introducing vaccines against COVID-19 under supply and uptake constraints in France: A modelling study
Authors: Coudeville Laurent , Jollivet Ombeline , Mahé Cedric , Chaves Sandra , Gomez Gabriela B.
Published: April 2021

Background

The accelerated vaccine development in response to the COVID-19 pandemic should lead to a vaccine being available early 2021, albeit in limited supply and possibly without full vaccine acceptance. We assessed the short-term impact of a COVID-19 immunization program with varying constraints on population health and non-pharmaceutical interventions (NPIs) needs.

Methods

A SARS-CoV-2 transmission model was calibrated to French epidemiological data. We defined several vaccine implementation scenarios starting in January 2021 based on timing of discontinuation of NPIs, supply and uptake constraints, and their relaxation. We assessed the number of COVID-19 hospitalizations averted, the need for and number of days with NPIs in place over the 2021–2022 period.

Results

An immunisation program under constraints could reduce the burden of COVID-19 hospitalizations by 9–40% if the vaccine prevents against infections. Relaxation of constraints not only reduces further COVID-19 hospitalizations (30–39% incremental reduction), it also allows for NPIs to be discontinued post-2021 (0 days with NPIs in 2022 versus 11 to 125 days for vaccination programs under constraints and 327 in the absence of vaccination).

Conclusion

For 2021, COVID-19 control is expected to rely on a combination of NPIs and the outcome of early immunisation programs. The ability to overcome supply and uptake constraints will help prevent the need for further NPIs post-2021. As the programs expand, efficiency assessments will be needed to ensure optimisation of control policies post-emergency use.
Development and psychometric properties of the Japanese Consumer Assessment of Healthcare Providers and Systems Clinician & Group Survey (CG-CAHPS)
Authors: Aoki Takuya , Taguchi Kuichiro , Hama Eiichi
Published: April 2021

The Consumer Assessment of Healthcare Providers and Systems Clinician & Group Survey (CG-CAHPS) is one of the most widely studied and endorsed patient experience measures for ambulatory care. This study aimed to develop a Japanese CG-CAHPS and examine its psychometric properties. We evaluated the structural validity, criterion-related validity, internal consistency reliability, and site-level reliability of the scale. Data were analyzed for 674 outpatients aged 18 years or older in 11 internal medicine clinics. The confirmatory factor analysis supported the scale’s structural validity and the same composites (Access, Provider Communication, Care Coordination, and Office Staff) as that of the original CG-CAHPS. All site-level Pearson correlation coefficients between the Japanese CG-CAHPS composites and overall provider rating exceeded the criteria. Results of item-total correlations and Cronbach’s alpha indicated adequate internal consistency reliability. We developed the Japanese CG-CAHPS and examined its validity and reliability to measure the quality of ambulatory care based on patient experience. The results of the Japanese CG-CAHPS survey will provide useful information to providers, organizations, and policy makers for achieving a patient-centered healthcare system in Japan.
The RNA helicase DDX5 promotes viral infection via regulating N6-methyladenosine levels on the DHX58 and NFκB transcripts to dampen antiviral innate immunity
Authors: Xu Jian , Cai Yunhong , Ma ZhenBang , Jiang Bo , Liu Wenxiao , Cheng Jing , Guo Nannan , Wang Zishu , Sealy Joshua E. , Song Cuiping , Wang Xiaojia , Li Yongqing
Published: April 2021

Multi-functional DEAD-box helicase 5 (DDX5), which is important in transcriptional regulation, is hijacked by diverse viruses to facilitate viral replication. However, its regulatory effect in antiviral innate immunity remains unclear. We found that DDX5 interacts with the N6-methyladenosine (m6A) writer METTL3 to regulate methylation of mRNA through affecting the m6A writer METTL3–METTL14 heterodimer complex. Meanwhile, DDX5 promoted the m6A modification and nuclear export of transcripts DHX58, p65, and IKKγ by binding conserved UGCUGCAG element in innate response after viral infection. Stable IKKγ and p65 transcripts underwent YTHDF2-dependent mRNA decay, whereas DHX58 translation was promoted, resulting in inhibited antiviral innate response by DDX5 via blocking the p65 pathway and activating the DHX58-TBK1 pathway after infection with RNA virus. Furthermore, we found that DDX5 suppresses antiviral innate immunity in vivo. Our findings reveal that DDX5 serves as a negative regulator of innate immunity by promoting RNA methylation of antiviral transcripts and consequently facilitating viral propagation.
Two StAR-related lipid transfer proteins play specific roles in endocytosis, exocytosis, and motility in the parasitic protist Entamoeba histolytica
Authors: Das Koushik , Watanabe Natsuki , Nozaki Tomoyoshi
Published: April 2021

Lipid transfer proteins (LTPs) are the key contributor of organelle-specific lipid distribution and cellular lipid homeostasis. Here, we report a novel implication of LTPs in phagocytosis, trogocytosis, pinocytosis, biosynthetic secretion, recycling of pinosomes, and motility of the parasitic protist E. histolytica, the etiological agent of human amoebiasis. We show that two StAR-related lipid transfer (START) domain-containing LTPs (named as EhLTP1 and 3) are involved in these biological pathways in an LTP-specific manner. Our findings provide novel implications of LTPs, which are relevant to the elucidation of pathophysiology of the diseases caused by parasitic protists.
Facilitating educational opportunities and raised self-esteem in disadvantaged young people in South East Wales: Effects of the Junior Rock Music Academy widening participation programme
Authors: Ellis Jane
Published: April 2021

This study examined the effects of the Junior Rock Music Academy (JRMA) on participants’ (N = 39) confidence and self-esteem. The JRMA was a widening participation Saturday music programme developed to reduce the influences of poverty on educational underachievement for young people (10–18 years) from poorer families across South East Wales. Participants’ confidence and self-esteem scores reported a significant rise, with no significant difference reported between genders or age groups. Participants (N = 5), programme tutors (N = 3) and participant parents/guardians (N = 4) were interviewed using semi-structured interviews to establish the fidelity of the structure and content of the intervention. The impact of JRMA on the psychosocial, cultural and emotional characteristics of participants and their parents/guardians as barriers to educational attainment and preparedness to thrive in education are discussed; these include enhanced cognitive development, social and emotional skills and learner motivation.
Building the youth music industry in South Wales, 1996–2020
Authors: Griffiths Spike
Published: April 2021

This article shines a light on the tailored and targeted popular music provision provided by Sonig, Rhondda Cynon Taf County Borough Council’s (RCTCBC) long-standing music industry programme. Over a twenty-year period, Sonig has successfully engaged with young people in disenfranchised areas of South Wales, many of whom have never experienced a way of accessing the music industry. Through workshops, masterclasses, performance opportunities, mentoring, networking and signposting career pathways, Sonig has become a new gateway for young talent. Creating these pathways is key to an equality of access and furthermore, enabling young people to reach their creative potential, through developing confidence, self-esteem and raising their aspirations. This article tracks the history of Sonig and provides a focus on how its constant evolution has positively intervened in the lives of many young people living in Wales.
An equal opportunity: Using technology to engage young people in Welsh music making
Authors: Parton Simon
Published: April 2021

Through his work as a self-employed music tutor based in the coastal city of Swansea, the author has found that many young people can regard making music as a difficult or even impossible thing to achieve – whether this means playing guitar, producing music, composing a song, writing lyrics or singing. This article examines some of the techniques employed by the author to break down a range of social and personal barriers in students, using technology as a creative medium. It also outlines some of the success stories of participants who have engaged in his teaching programme.
Comparison of Clinical and Biochemical Markers of Hirsutism in Polycystic Ovary Syndrome – A Study from a Teaching Hospital in Sri Ramachandra Institute, Chennai, India
Authors: Logaprabhu Nandhini , Murugesan Sarmishta
Published: April 2021

BACKGROUND We wanted to analyse the clinical profile of polycystic ovarian syndrome (PCOS) women with history, examination and ultrasonogram and correlate hirsutism with biochemical markers as free testosterone, dehydro-epiandrosterone sulphate (DHEAS), sex hormone binding globulin (SHBG), free testosterone, DHEAS, and SHBG. METHODS This study is a prospective observational study conducted from 2011 to 2013 in the Department of Obstetrics and Gynaecology, Shree Balaji Medical College and Hospital, Chrompet in patients attending Gynaecology OPD. 100 women visiting the OPD were taken as control and 100 women were taken for PCOS study. RESULTS Hyperandrogenism was studied and all the biochemical markers were significantly higher in polycystic ovarian syndrome patients than in controls (P < 0.0001). The highest AUC-ROC was found for bioavailable testosterone (0.852) followed by free androgen index (0.847) and free testosterone (0.837). Lower AUC-ROC was found for androstenedione, total testosterone and SHBG (0.706, 0.799 and 0.76, respectively). When free androgen index of 4.97 was taken as a cut off value, sensitivity was 71.4 % and specificity was 85.2 %. A cut off of 0.78 nmol / L for bioavailable testosterone had even higher sensitivity of 75.9 %, but slightly lower specificity of 83.3 %. Bioavailable testosterone and free androgen index correlated significantly (all P < 0.05) with DHEAS, LH / FSH ratio, androstenedione and total testosterone. In addition, bioavailable testosterone, free androgen index, and free testosterone correlated significantly with follicle count, ovarian volume, and hirsutism scores. CONCLUSIONS White women have about 20 % of excess of dehydro-epiandrosterone sulphate (DHEAS) and black women have 30 % excess of dehydro-epiandrosterone sulphate (DHEAS) in those having poly cystic ovaries patients. There is an age-associated decline in DHEAS levels which is similar in both control and poly cystic ovaries women, regardless of the race which was seen in this study. KEY WORDS Free Testosterone, Dehydro–Epiandrosterone Sulphate (DHEAS), Sex Hormone Binding Globulin (SHBG)
Prosthetic Rehabilitation of Maxillectomy Defects, with Single-Piece Open-Hollow Bulb Definitive Obturator
Authors: Mishra Ananya , Mohamed Kasim , Kumar Prasanna , Jayagandhi Sathish Kumar
Published: April 2021

Patients who undergo surgical resection of the maxillo-mandibular structures as a result of trauma, infection or malignancy, suffer from psycho-social setbacks which has a profound impact on their over-all quality of life. 1,2 These defects, especially those following maxillectomy, result in oroantral communication, facial deformation, impaired speech and difficulty in deglutition. For the rehabilitation of patients with such defects, surgical and prosthetic treatment options are available. As, not all patients can be successfully rehabilitated with reconstructive surgeries due to postoperative complications like graft rejection, the extent of the surgical defect and high psychological impact factor associated with repeated surgeries, prosthetic rehabilitation proves to be an alternative treatment option. The prosthetic rehabilitation of such patients is challenging as it requires restoration of the lost form, function and aesthetics, under constantly changing state of post-surgical intraoral tissues, with limited mouth opening. The maxillofacial prosthesis designed to close congenital or an acquired tissue opening, primarily of the hard palate, is known as an obturator. 3 The obturator has two functional components, one seals the surgical defect and the other replaces the lost dentoalveolarstructures.4-7 The design of an obturator may vary depending on the extent of the defect, remnant dentoalveolar complex, soft tissue undercuts and existent muscle physiology.8,9 Among the two designs, solid and hollow, hollow obturators are widely used. The bulb portion of the hollow obturator, which accommodates the surgical defect, can be open or closed9,10and its selection depends on the prosthodontist’s clinical decision-making skills and the ease of fabrication. In this article we have discussed the rehabilitated patients with single-piece, openhollow bulb definitive obturator. Patients undergo extensive maxillary surgical resections due to aggressive lesions like malignancies and deep fungal infections. Prosthetic rehabilitation of such patients with an obturator becomes of paramount importance as it separates the oropharynx from the nasopharynx, reduces the risk of recurrent infections, replaces lost dentoalveolar structures, permits intelligible speech, reinstates mastication and deglutition, restores facial contour and patient’s self-esteem. The bulb portion of the obturator extends into the defect and accommodates it, forming a hermetic seal. In this clinical report, we highlight the success of prosthetic rehabilitation of maxillectomy patients using single-piece, open-hollow bulb definitive obturator. The meticulous follow-up carried out reveals the success of the prosthesis and adds practice-based evidence to the maxillectomy rehabilitation outcome.
Nursing Care Management of Chronic Myeloid Leukemia – A Case Report
Authors: Sheikh Shakib Hasan , Tembhare Vaishali , Singh Seema , Pohekar Savita , Gujar Samruddhi
Published: April 2021

Excessive growth of mature granulocytes in the bone marrow induces chronic myeloid leukemia. The excess neoplastic granulocytes travel massively into the peripheral blood and in the end invade the liver and spleen. The protein encoded on the Philadelphia chromosome by the newly created BCR-ABL gene interferes with normal cell cycle activities, including regulating cell proliferation. Philadelphia chromosome is present in 90 - 95 percent of chronic myeloid leukemia (CML) patients. Their involvement is often a vital indicator of persistent disease or posttreatment relapse. However, for the diagnosis of CML, the presence of the Philadelphia chromosome is not specific since it is also present in acute lymphocytic leukemia (ALL) and rarely in acute myeloid leukemia (AML). 1 Chronic myeloid leukemia is a myeloproliferative neoplasm (MPN) characterised by involvement of the fusion gene BCRABL1 located in the Philadelphia chromosome. In reactive neutrophilia or chronic neutrophilic leukemia, the Ph chromosome is pathognomonic to CML and is never registered.2,3