bluuebunny/crossref_metadata_2025 huggingface dataset:
Time-encoded mid-infrared Fourier-domain optical coherence tomography
Authors: Zorin Ivan , Gattinger Paul , Prylepa Andrii , Heise Bettina
Published: July 2021

We report on a technically simple approach to achieve high-resolution and high-sensitivity Fourier-domain optical coherence tomography (OCT) imaging in the mid-infrared (mid-IR) range. The proposed OCT system employs an

I
n
F

3

supercontinuum source. A specially designed dispersive scanning spectrometer based on a single InAsSb point detector is employed for detection. The spectrometer enables structural OCT imaging in the spectral range from 3140 nm to 4190 nm with a characteristic sensitivity of over 80 dB and an axial resolution below

8

µ

m

. The capabilities of the system are demonstrated for imaging of porous ceramic samples and transition-stage green parts fabricated using an emerging method of lithography-based ceramic manufacturing. Additionally, we demonstrate the performance and flexibility of the system by OCT imaging using an inexpensive low-power (average power of 16 mW above

3

µ

m

wavelength) mid-IR supercontinuum source.
Structure of the human C9orf72-SMCR8 complex reveals a multivalent protein interaction architecture
Authors: Nörpel Julia , Cavadini Simone , Schenk Andreas D. , Graff-Meyer Alexandra , Hess Daniel , Seebacher Jan , Chao Jeffrey A. , Bhaskar Varun
Published: July 2021

A major cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) spectrum disorder is the hexanucleotide G4C2repeat expansion in the first intron of the C9orf72 gene. Many underlying mechanisms lead to manifestation of disease that include toxic gain-of-function by repeat G4C2RNAs, dipeptide repeat proteins, and a reduction of the C9orf72 gene product. The C9orf72 protein interacts with SMCR8 and WDR41 to form a trimeric complex and regulates multiple cellular pathways including autophagy. Here, we report the structure of the C9orf72-SMCR8 complex at 3.8 Å resolution using single-particle cryo-electron microscopy (cryo-EM). The structure reveals 2 distinct dimerization interfaces between C9orf72 and SMCR8 that involves an extensive network of interactions. Homology between C9orf72-SMCR8 and Folliculin-Folliculin Interacting Protein 2 (FLCN-FNIP2), a GTPase activating protein (GAP) complex, enabled identification of a key residue within the active site of SMCR8. Further structural analysis suggested that a coiled-coil region within the uDenn domain of SMCR8 could act as an interaction platform for other coiled-coil proteins, and its deletion reduced the interaction of the C9orf72-SMCR8 complex with FIP200 upon starvation. In summary, this study contributes toward our understanding of the biological function of the C9orf72-SMCR8 complex.
A conserved ubiquitin- and ESCRT-dependent pathway internalizes human lysosomal membrane proteins for degradation
Authors: Zhang Weichao , Yang Xi , Chen Liang , Liu Yun-Yu , Venkatarangan Varsha , Reist Lucas , Hanson Phyllis , Xu Haoxing , Wang Yanzhuang , Li Ming
Published: July 2021

The lysosome is an essential organelle to recycle cellular materials and maintain nutrient homeostasis, but the mechanism to down-regulate its membrane proteins is poorly understood. In this study, we performed a cycloheximide (CHX) chase assay to measure the half-lives of approximately 30 human lysosomal membrane proteins (LMPs) and identified RNF152 and LAPTM4A as short-lived membrane proteins. The degradation of both proteins is ubiquitin dependent. RNF152 is a transmembrane E3 ligase that ubiquitinates itself, whereas LAPTM4A uses its carboxyl-terminal PY motifs to recruit NEDD4-1 for ubiquitination. After ubiquitination, they are internalized into the lysosome lumen by the endosomal sorting complexes required for transport (ESCRT) machinery for degradation. Strikingly, when ectopically expressed in budding yeast, human RNF152 is still degraded by the vacuole (yeast lysosome) in an ESCRT-dependent manner. Thus, our study uncovered a conserved mechanism to down-regulate lysosome membrane proteins.
Experimental and molecular predictions of the adjuvanticity of snail mucin on hepatitis B vaccine in albino mice
Authors: Joshua Parker Elijah , Nwauzor Cynthia Ogochukwu , Odimegwu Damian Chukwu , Ukachukwu Uzochukwu Gospel , Asomadu Rita Onyekachukwu , Ezeorba Timothy Prince Chidike
Published: July 2021

Although aluminum-containing adjuvants are widely used in human vaccination due to their excellent safety profile, they exhibit low effectiveness with many recombinant antigens. This study investigated the adjuvanticity of snail mucin with recombinant Hepatitis B Vaccine (rHBsAg). Twenty-five (25) female mice distributed unbiasedly into 5 groups were used in the study and were administered different rHBsAg/Mucin formulation at 7 days intervals. Blood samples were collected a day following the administration for analysis. The results of liver function and body weight analysis were indications that snail mucin had no adverse effect on the mice. The treatment group (administer mucin and rHBsAg) showed significantly (P<0.05) higher mean titres of anti-HBsAg antibodies when compared with the negative controls and the positive control administered with two doses of rHBsAg after the boost doses (day 28). Furthermore, a comparable immune response to positive control administered with three doses rHBaAG was recorded. In silico prediction, studies of the protein-protein interaction of a homology modelled snail mucus protein and HBsAg gave an indication of enhanced HBV antigen-antibody interaction. Therefore, this study has shown that snail mucin possesses some adjuvant properties and enhances immune response towards rHBsAg vaccine. However, there is a need for further molecular dynamics studies to understand its mechanism of action.
SecSel, a new software tool for conservation prioritization that is applicable to ordinal-scale data for multiple biodiversity features
Authors: Akio Takenaka , Hiroyuki Oguma , Yukihiro Amagai , Fumiko Ishihama
Published: July 2021

SecSel, a protected-area prioritization tool, has been developed to help design areas that efficiently protect multiple features, including conservation of biodiversity and use of ecosystem services. The prioritization by SecSel is based on evaluation of the local units of each feature. The evaluation metrics should be quantitative but need not be ratio scale. The minimum requirement of the input data is that they are ordinal. The conservation target is the number of local units with high values of each feature to be protected in the area. SecSel can handle conflicts among features, including conflicts between conservation and utilization of land or specific ecosystem functions. Before the selection procedure, one of a conflicting pair of features in a site is discarded. That decision is based on the dispensability of the local unit to fulfilling the conservation target of each feature. SecSel also considers the cost of including each site in the protected area and the compactness of the area in terms of total boundary length or the distance to the nearest site. To demonstrate the functionality of Secsel, we used it to design land use in an alpine region of northern Japan where conservation of alpine vegetation and its recreational use are important considerations.
On the way to routine cardiac MRI at 7 Tesla - a pilot study on consecutive 84 examinations
Authors: Reiter Theresa , Lohr David , Hock Michael , Ankenbrand Markus Johannes , Stefanescu Maria Roxana , Kosmala Aleksander , Kaspar Mathias , Juchem Christoph , Terekhov Maxim , Schreiber Laura Maria
Published: July 2021

Introduction

Cardiac magnetic resonance (CMR) at ultrahigh field (UHF) offers the potential of high resolution and fast image acquisition. Both technical and physiological challenges associated with CMR at 7T require specific hardware and pulse sequences. This study aimed to assess the current status and existing, publicly available technology regarding the potential of a clinical application of 7T CMR.

Methods

Using a 7T MRI scanner and a commercially available radiofrequency coil, a total of 84 CMR examinations on 72 healthy volunteers (32 males, age 19–70 years, weight 50–103 kg) were obtained. Both electrocardiographic and acoustic triggering were employed. The data were analyzed regarding the diagnostic image quality and the influence of patient and hardware dependent factors. 50 complete short axis stacks and 35 four chamber CINE views were used for left ventricular (LV) and right ventricular (RV), mono-planar LV function, and RV fractional area change (FAC). Twenty-seven data sets included aortic flow measurements that were used to calculate stroke volumes. Subjective acceptance was obtained from all volunteers with a standardized questionnaire.

Results

Functional analysis showed good functions of LV (mean EF 56%), RV (mean EF 59%) and RV FAC (mean FAC 52%). Flow measurements showed congruent results with both ECG and ACT triggering. No significant influence of experimental parameters on the image quality of the LV was detected. Small fractions of 5.4% of LV and 2.5% of RV segments showed a non-diagnostic image quality. The nominal flip angle significantly influenced the RV image quality.

Conclusion

The results demonstrate that already now a commercially available 7T MRI system, without major methods developments, allows for a solid morphological and functional analysis similar to the clinically established CMR routine approach. This opens the door towards combing routine CMR in patients with development of advanced 7T technology.
Comparing the impact of an icon array versus a bar graph on preference and understanding of risk information: Results from an online, randomized study
Authors: Scalia Peter , Schubbe Danielle C. , Lu Emily S. , Durand Marie-Anne , Frascara Jorge , Noel Guillermina , O’Malley A. James , Elwyn Glyn
Published: July 2021

Background

Few studies have examined the best way to convey the probability of serious events occurring in the future (i.e., risk of stroke or death) to persons with low numeracy or graph literacy proficiency. To address this gap, we developed and user-tested a bar graph and compared it to icon arrays to assess its impact on understanding and preference for viewing risk information.

Objectives

To determine the: (i) formats’ impact on participants’ understanding of risk information; (ii) formats’ impact on understanding and format preference across numeracy and graph literacy subgroups; (iii) rationale supporting participants’ preference for each graphical display format.

Methods

An online sample (evenly made up of participants with high and low objective numeracy and graph literacy) was randomized to view either the icon array or the bar graph. Each format conveyed the risk of major stroke and death five years after choosing surgery, a stent, or medication to treat carotid artery stenosis. Participants answered questions to assess their understanding of the risk information. Lastly, both formats were presented in parallel, and participants were asked to identify their preferred format to view risk information and explain their preference.

Results

Of the 407 participants, 197 were assigned the icon array and 210 the bar graph. Understanding of risk information and format preference did not differ significantly between the two trial arms, irrespective of numeracy and graph literacy proficiency. High numeracy and graph literacy proficiency was associated with high understanding (p<0.01) and a preference for the bar graph (p = 0.01).

Conclusion

We found no evidence to demonstrate the superiority of one format over another on understanding. The majority of participants preferred viewing the risk information using the bar graph format.
Endpoint PCR coupled with capillary electrophoresis (celPCR) provides sensitive and quantitative measures of environmental DNA in singleplex and multiplex reactions
Authors: Thalinger Bettina , Pütz Yannick , Traugott Michael
Published: July 2021

The use of sensitive methods is key for the detection of target taxa from trace amounts of environmental DNA (eDNA) in a sample. In this context, digital PCR (dPCR) enables direct quantification and is commonly perceived as more sensitive than endpoint PCR. However, endpoint PCR coupled with capillary electrophoresis (celPCR) potentially embodies a viable alternative as it quantitatively measures signal strength after PCR in Relative Fluorescence Units (RFU). Provided comparable levels of sensitivity are reached, celPCR permits the development of cost-efficient multiplex reactions, enabling the simultaneous detection of several target taxa. Here, we compared the sensitivity of singleplex and multiplex celPCR to dPCR for species-specific primer pairs amplifying mitochondrial DNA (COI) of fish species occurring in European freshwaters by analyzing dilution series of tissue extracts as well as field-collected water samples. Both singleplex and multiplex celPCR and dPCR displayed comparable sensitivity with reliable positive amplifications starting at two to 10 target DNA copies per μl extract. celPCR was suitable for quantifying target DNA and direct inference of copy numbers from RFU was possible after accounting for primer effects in linear mixed-effects models and calibration via dPCR. Furthermore, multiplex celPCR and dPCR were successfully used for the detection and quantification of fish-eDNA in field-collected water samples, confirming the results of the dilution series experiment and exemplifying the high sensitivity of the two approaches. The possibility of detection and quantification via multiplex celPCR is appealing for the cost-efficient screening of high sample numbers. The present results confirm the sensitivity of this approach thus enabling its application for future eDNA-based monitoring efforts.
A huggable device can reduce the stress of calling an unfamiliar person on the phone for individuals with ASD
Authors: Sumioka Hidenobu , Kumazaki Hirokazu , Muramatsu Taro , Yoshikawa Yuichiro , Ishiguro Hiroshi , Higashida Haruhiro , Yuhi Teruko , Mimura Masaru
Published: July 2021

Individuals with autism spectrum disorders (ASD) are often not comfortable during mobile-phone conversations with unfamiliar people. “Hugvie” is a pillow with a human-like shape that has been designed to provide users with the tactile sensation of hugging another person during phone conversations to promote feelings of comfort and trust in the speaker toward their conversation partners. Our primary aim was to examine whether physical contact by hugging a Hugvie could reduce the stress of speaking with an unfamiliar person on the phone in individuals with ASD. We enrolled 24 individuals and requested them to carry out phone conversations either using only a mobile phone or using a mobile phone along with the Hugvie. All participants in both groups completed questionnaires designed to evaluate their self-confidence while talking on the phone, and also provided salivary cortisol samples four times each day. Our analysis revealed that the medium of communication was a significant factor, indicating that individuals with ASD who spoke with an unfamiliar person on the phone while hugging a Hugvie had stronger self-confidence and lower stress levels than those who did not use Hugvie. Hence, we recommend that huggable devices be used as adjunctive tools to support individuals with ASD during telephonic conversations with unfamiliar people.
Improving quality of care for pregnancy, perinatal and newborn care at district and sub-district public health facilities in three districts of Haryana, India: An Implementation study
Authors: Das Manoja Kumar , Arora Narendra Kumar , Dalpath Suresh Kumar , Kumar Saket , Kumar Amneet P. , Khanna Abhishek , Bhatnagar Ayushi , Bahl Rajiv , Nisar Yasir Bin , Qazi Shamim Ahmad , Arora Gulshan Kumar , Dhankhad R. K. , Kumar Krishan , Chander Ramesh , Singh Bhanwar
Published: July 2021

Introduction

Improving quality of care (QoC) for childbirth and sick newborns is critical for maternal and neonatal mortality reduction. Information on the process and impact of quality improvement at district and sub-district hospitals in India is limited. This implementation research was prioritized by the Haryana State (India) to improve the QoC for maternal and newborn care at the busy hospitals in districts.

Methods

This study at nine district and sub-district referral hospitals in three districts (Faridabad, Rewari and Jhajjar) during April 2017-March 2019 adopted pre-post, quasi-experimental study design and plan-do-study-act quality improvement method. During the six quarterly plan-do-study-act cycles, the facility and district quality improvement teams led the gap identification, solution planning and implementation with external facilitation. The external facilitators monitored and collected data on indicators related to maternal and newborn service availability, patient satisfaction, case record quality, provider’s knowledge and skills during the cycles. These indicators were compared between baseline (pre-intervention) and endline (post-intervention) cycles for documenting impact.

Results

The interventions closed 50% of gaps identified, increased the number of deliveries (1562 to 1631 monthly), improved care of pregnant women in labour with hypertension (1.2% to 3.9%, p<0.01) and essential newborn care services at birth (achieved ≥90% at most facilities). Antenatal identification of high-risk pregnancies increased from 4.1% to 8.8% (p<0.01). Hand hygiene practices improved from 35.7% to 58.7% (p<0.01). The case record completeness improved from 66% to 87% (p<0.01). The time spent in antenatal clinics declined by 19–42 minutes (p<0.01). The pooled patient satisfaction scores improved from 82.5% to 95.5% (p<0.01). Key challenges included manpower shortage, staff transfers, leadership change and limited orientation for QoC.

Conclusion

This multipronged quality improvement strategy improved the maternal and newborn services, case documentation and patient satisfaction at district and sub-district hospitals. The processes and lessons learned shall be useful for replicating and scaling up.
TREND database: Retinal images of healthy young subjects visualized by a portable digital non-mydriatic fundus camera
Authors: Popovic Natasa , Vujosevic Stela , Radunović Miroslav , Radunović Miodrag , Popovic Tomo
Published: July 2021

Topological characterization of the Retinal microvascular nEtwork visualized by portable fuNDus camera (TREND) is a database comprising of 72 color digital retinal images collected from the students of the Faculty of Medicine at the University of Montenegro, in the period from February 18th to March 11th 2020. The database also includes binarized images of manually segmented microvascular networks associated with each raw image. The participant demographic characteristics, health status, and social habits information such as age, sex, body mass index, smoking history, alcohol use, as well as previous medical history was collected. As proof of the concept, a smaller set of 10 color digital fundus images from healthy older participants is also included. Comparison of the microvascular parameters of these two sets of images demonstrate that digital fundus images recorded with a hand-held portable camera are able to capture the changes in patterns of microvascular network associated with aging. The raw images from the TREND database provide a standard that defines normal retinal anatomy and microvascular network geometry in young healthy people in Montenegro as it is seen with the digital hand-held portable non-mydriatic MiiS HORUS Scope DEC 200.This knowledge could facilitate the application of this technology at the primary level of health care for large scale telematic screening for complications of chronic diseases, such as hypertensive and diabetic retinopathy. In addition, it could aid in the development of new methods for early detection of age-related changes in the retina, systemic chronic diseases, as well as eye-specific diseases. The associated manually segmented images of the microvascular networks provide the standard that can be used for development of automatic software for image quality assessment, segmentation of microvascular network, and for computer-aided detection of pathological changes in retina. The TREND database is freely available at https://doi.org/10.5281/zenodo.4521043.
Mothers’ utilization and associated factors of preconception care in Africa, a systematic review and meta-analysis
Authors: Tekalign Tiwabwork , Lemma Tesfanesh , Silesh Mulualem , Lake Eyasu Alem , Teshome Mistire , Yitna Tesfaye , Awoke Nefsu
Published: July 2021

Background

As the studies show, in every minute in the world, 380 women become pregnant and 190 face unplanned or unwanted pregnancies; 110 experience pregnancy-related complications, and one woman dies from a pregnancy-related cause. Preconception care is one of the proven strategies for the reduction in mortality and decreases the risk of adverse health effects for the woman, fetus, and neonate by optimizing maternal health services and improves woman’s health. Therefore, this study aimed to estimate the pooled prevalence of utilization of preconception of care and associated factors in Africa.

Methods

Systematic search of published studies done on PubMed, EMBASE, MEDLINE, Cochrane, Scopus, Web of Science CINAHL, and manually on Google Scholar. This meta-analysis follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The quality of studies was assessed by the modified Newcastle-Ottawa Scale (NOS). Meta-analysis was carried out using a random-effects method using the STATA™ Version 14 software.

Result

From 249,301 obtained studies, 28 studies from 3 African regions involving 13067 women included in this Meta-analysis. The overall pooled prevalence of utilization of preconception care among pregnant women in Africa was found to be 18.72% (95% CI: 14.44, 23.00). Knowledge of preconception care (P = <0.001), preexisting medical condition (P = 0.045), and pregnancy intention (P = 0.016) were significantly associated with the utilization of preconception care.

Conclusion

The results of this meta-analysis indicated, as one of best approaches to improve birth outcomes, the utilization of preconception care is significantly low among mothers in Africa. Therefore, health care organizations should work on strategies to improve preconception care utilization.
Effects of self-management programs on behavioral modification among individuals with chronic disease: A systematic review and meta-analysis of randomized trials
Authors: Kim Sunju , Park Moonkyoung , Song Rhayun
Published: July 2021

The prevalence of chronic disease associated with unhealthy lifestyles has been increasing worldwide. Health professionals have recognized that self-management programs (SMPs) can provide health benefits by promoting health behaviors, especially when applied to individuals with lifestyle-related chronic disease. This review performed a meta-analysis of the features of SMPs using randomized studies and analyzed the magnitude of the combined effects of self-management on behavioral modification. We searched the PubMed, CINAHL, ScienceDirect, SCOPUS, Web of Science, Embase, Cochrane Library, DBpia, and KISS to identify randomized trials that evaluated the behavioral outcomes of SMPs. Subgroup analyses were performed for program duration, providers, type of comparisons, and program settings. We selected 25 studies (N = 5,681) to perform analyses with random-effects models. The effect sizes of SMPs were small but significant for physical activity (standardized difference in means [SDM] = 0.25), dietary habits (SDM = 0.28), and health responsibility (SDM = 0.18), and not significant for stress management and smoking behaviors. A short-term SMPs (less than 12 weeks) was indicated as being effective in modifying physical activity, dietary habits, and health responsibility, while the program effects on dietary habits were significant only with expert-delivered education and when compared with inactive controls. The findings of this study indicate that SMPs can effectively improve physical activity, dietary habits, and health responsibility in individuals with chronic disease, with a small but significant effect size. Future studies should explore the effects of SMPs on stress management and smoking cessation and assess the long-term maintenance of healthy lifestyles in individuals with lifestyle-related chronic disease.
Pathogenicity of local and exotic entomopathogenic fungi isolates against different life stages of red palm weevil (Rhynchophorus ferrugineus)
Authors: Sutanto Koko Dwi , Husain Mureed , Rasool Khawaja Ghulam , Al-Qahtani Wahidah Hazza , Aldawood Abdulrahman Saad
Published: July 2021

Entomopathogenic fungi are regarded as effective biocontrol agents in pest management. Different fungi isolates exhibit varying degree of pathogenicity against red palm weevil [Rhynchophorus ferrugineus(Olivier)]. The pathogenicity of four native isolate from Saudi Arabia (threeBeauveria bassiananamed as BbSA-1, BbSA-2, BbSA-3 and oneMetarhizium anisopliaeregarded as MaSA-1) and three exotic isolates from Indonesia (B.bassianacoded as BbIDN-1 andM.anisopliaenamed as MaIDN-1 and MaIDN-2) was evaluated against red palm weevil under laboratory conditions. The isolates were applied to eggs (1 day old), larvae (3 and 35 days old), pupae (5 days old) and adults (10 days old). The average mortality rate of eggs and hatched larvae was 100% in all of the isolates except BbSA-2 and BbIDN-1, where mortality was 93.3 and 90%, respectively. The lowest mortality rate (73.3%) was recorded for BbSA-3 against 3-days-old larvae; however, all other isolates caused >80% larval mortality. Meanwhile, 93.3% mortality of 35-day-old larvae was noted for MaSA-1 isolate. The highest pupa mortality (80%) was observed for MaSA-1, while remaining isolates caused >60% mortality. The isolates BbSA-1 and MaSA-1 caused 61 and 74.3% mortality in adults, respectively. The tested fungi isolates exhibited high virulence against all life stages of red palm weevil. Local isolates had higher pathogenicity than exotic isolates. The findings of the current study suggest that entomopathogenic fungi could be used as biological control agents for the management of red palm weevil. However, field studies are needed to reach the sound conclusions and practical applications.
Ethical review of COVID-19 research in the Netherlands; a mixed-method evaluation among medical research ethics committees and investigators
Authors: IJkema R. , Janssens M. J. P. A. , van der Post J. A. M. , Licht C. M.
Published: July 2021

Background

During the beginning of the COVID-19 pandemic there was an urgent need for accelerated review of COVID-19 research by Medical Research Ethics Committees (MRECs). In the Netherlands this led to the implementation of so-called ‘fast-track-review-procedures’ (FTRPs) to enable a swift start of urgent and relevant research. The objective of this study is to evaluate FTRPs of MRECs in the Netherlands during the COVID-19 pandemic and to compare them with the regular review procedures (RRPs).

Methods and findings

An explanatory sequential mixed method study was conducted. Online questionnaires and four group interviews were conducted among MREC representatives and investigators of COVID-19 research. In addition, data from a national research registration system was requested. Main outcome measures are differences in timelines, quality of the review and satisfaction between FTRPs and RRPs. The total number of review days was shorter in FTRP (median 10.5) compared to RRPs (median 98.0). Review days attributable to the MRECs also declined in FTRPs (median 8.0 versus 50.0). This shortening can be explained by installing ad hoc (sub)committees, full priority given to COVID-19 research, regular research put on hold, online review meetings and administrative leniency. The shorter timelines did not affect the perceived quality of the review and ethical and legal aspects were not weighted differently. Both MREC representatives and investigators were generally satisfied with the review of COVID-19 research. Weaknesses identified were the lack of overview of COVID-19 research and central collaboration and coordination, the delay of review of regular research, and limited reachability of secretariats.

Conclusions

This study shows that accelerated review is feasible during emergency situations. We did not find evidence that review quality was compromised and both investigators and MRECs were content with the FTRP. To improve future medical ethical review during pandemic situations and beyond, distinguishing main and side issues, working digitally, and (inter)national collaboration and coordination are important.
The synchronicity of COVID-19 disparities: Statewide epidemiologic trends in SARS-CoV-2 morbidity, hospitalization, and mortality among racial minorities and in rural America
Authors: Dixon Brian E. , Grannis Shaun J. , Lembcke Lauren R. , Valvi Nimish , Roberts Anna R. , Embi Peter J.
Published: July 2021

Background

Early studies on COVID-19 identified unequal patterns in hospitalization and mortality in urban environments for racial and ethnic minorities. These studies were primarily single center observational studies conducted within the first few weeks or months of the pandemic. We sought to examine trends in COVID-19 morbidity, hospitalization, and mortality over time for minority and rural populations, especially during the U.S. fall surge.

Methods

Data were extracted from a statewide cohort of all adult residents in Indiana tested for SARS-CoV-2 infection between March 1 and December 31, 2020, linked to electronic health records. Primary measures were per capita rates of infection, hospitalization, and death. Age adjusted rates were calculated for multiple time periods corresponding to public health mitigation efforts. Comparisons across time within groups were compared using ANOVA.

Results

Morbidity and mortality increased over time with notable differences among sub-populations. Initially, hospitalization rates among racial minorities were 3–4 times higher than whites, and mortality rates among urban residents were twice those of rural residents. By fall 2020, hospitalization and mortality rates in rural areas surpassed those of urban areas, and gaps between black/brown and white populations narrowed. Changes across time among demographic groups was significant for morbidity and hospitalization. Cumulative morbidity and mortality were highest among minority groups and in rural communities.

Conclusions

The synchronicity of disparities in COVID-19 by race and geography suggests that health officials should explicitly measure disparities and adjust mitigation as well as vaccination strategies to protect those sub-populations with greater disease burden.
Prevalence of complications associated with the use of a peripherally inserted central catheter in newborns: A systematic review protocol
Authors: Sarmento Diniz Edienne Rosângela , de Medeiros Kleyton Santos , Rosendo da Silva Richardson Augusto , Cobucci Ricardo Ney , Roncalli Angelo Giuseppe
Published: July 2021

Background

The improper handling of a peripherally inserted central catheter (PICC) in newborns (NBs) may result in mechanical and infectious complications.

Aim

The aim of this systematic review (SR) is to estimate the prevalence of complications associated with the use of PICC in NBs.

Methods

We will utilize PubMed, Embase, CENTRAL, Web of Science, Scopus, Cochrane Library, CINAHL, and Google Scholar for the databases search. There will be no restrictions on the search for languages, and observational studies will be selected wherein the prevalence rate of complications associated with the use of PICC in NBs has been presented or can be calculated. The systematic review will follow the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Two reviewers will independently select studies and assess their eligibility using predefined criteria. Using standardized forms, two other reviewers will independently extract data from each included study, and the random-effects pooled prevalence will be calculated in the meta-analysis with the respective 95% confidence intervals. The methodological quality of the studies will be assessed using the modified Newcastle-Ottawa Scale. Review Manager V.5.3.5 will be used for the qualitative and quantitative synthesis. A protocol was developed and published on PROSPERO (Registration number CRD42020211983).

Expected results

This SR will show the prevalence of complications caused by the inadequate management of PICC in NBs, which is information considered important for clinical practice improvement.
Rethinking remdesivir for COVID-19: A Bayesian reanalysis of trial findings
Authors: Hoek Joyce M. , Field Sarahanne M. , de Vries Ymkje Anna , Linde Maximilian , Pittelkow Merle-Marie , Muradchanian Jasmine , van Ravenzwaaij Don
Published: July 2021

Background

Following testing in clinical trials, the use of remdesivir for treatment of COVID-19 has been authorized for use in parts of the world, including the USA and Europe. Early authorizations were largely based on results from two clinical trials. A third study published by Wang et al. was underpowered and deemed inconclusive. Although regulators have shown an interest in interpreting the Wang et al. study, under a frequentist framework it is difficult to determine if the non-significant finding was caused by a lack of power or by the absence of an effect. Bayesian hypothesis testing does allow for quantification of evidence in favor of the absence of an effect.

Findings

Results of our Bayesian reanalysis of the three trials show ambiguous evidence for the primary outcome of clinical improvement and moderate evidence against the secondary outcome of decreased mortality rate. Additional analyses of three studies published after initial marketing approval support these findings.

Conclusions

We recommend that regulatory bodies take all available evidence into account for endorsement decisions. A Bayesian approach can be beneficial, in particular in case of statistically non-significant results. This is especially pressing when limited clinical efficacy data is available.
SARS-CoV-2 variant evolution in the United States: High accumulation of viral mutations over time likely through serial Founder Events and mutational bursts
Authors: Tasakis Rafail Nikolaos , Samaras Georgios , Jamison Anna , Lee Michelle , Paulus Alexandra , Whitehouse Gabrielle , Verkoczy Laurent , Papavasiliou F. Nina , Diaz Marilyn
Published: July 2021

Since the first case of COVID-19 in December 2019 in Wuhan, China, SARS-CoV-2 has spread worldwide and within a year and a half has caused 3.56 million deaths globally. With dramatically increasing infection numbers, and the arrival of new variants with increased infectivity, tracking the evolution of its genome is crucial for effectively controlling the pandemic and informing vaccine platform development. Our study explores evolution of SARS-CoV-2 in a representative cohort of sequences covering the entire genome in the United States, through all of 2020 and early 2021. Strikingly, we detected many accumulating Single Nucleotide Variations (SNVs) encoding amino acid changes in the SARS-CoV-2 genome, with a pattern indicative of RNA editing enzymes as major mutators of SARS-CoV-2 genomes. We report three major variants through October of 2020. These revealed 14 key mutations that were found in various combinations among 14 distinct predominant signatures. These signatures likely represent evolutionary lineages of SARS-CoV-2 in the U.S. and reveal clues to its evolution such as a mutational burst in the summer of 2020 likely leading to a homegrown new variant, and a trend towards higher mutational load among viral isolates, but with occasional mutation loss. The last quartile of 2020 revealed a concerning accumulation of mostly novel low frequency replacement mutations in the Spike protein, and a hypermutable glutamine residue near the putative furin cleavage site. Finally, end of the year data and 2021 revealed the gradual increase to prevalence of known variants of concern, particularly B.1.1.7, that have acquired additional Spike mutations. Overall, our results suggest that predominant viral genomes are dynamically evolving over time, with periods of mutational bursts and unabated mutation accumulation. This high level of existing variation, even at low frequencies and especially in the Spike-encoding region may become problematic when super-spreader events, akin to serial Founder Events in evolution, drive these rare mutations to prominence.
Genetic characterization of extended-spectrum β-Lactamase- and carbapenemase-producing Escherichia coli isolated from Egyptian hospitals and environments
Authors: El-Shaer Soha , Abdel-Rhman Shaymaa H. , Barwa Rasha , Hassan Ramadan
Published: July 2021

Over the past decades, Escherichia coli (E. coli) have acquired extensive resistance to antibiotics; especially β- lactams. This study aimed to investigate the frequency of Extended-spectrum β-lactamase (ESBL) and carbapenemase producers among E. coli isolates and their correlation with serotypes, phylogenetic background, and pathogenicity associated islands. A total of 105 E. coli strains were isolated and subjected to antimicrobial susceptibility testing against β-lactam antibiotics. All isolates showed a high resistance profile. Resistant isolates were tested for ESBL and carbapenemase production. Fifty-three and 18 isolates were positive for ESBL and carbapenemase producers, respectively. ESBL and carbapenemase genes were detected by PCR. TEM gene was the most prevalent gene among all isolates followed by SHV and CTX-M15. In carbapenemase-producers, OXA-48 and IMP were the predominant genes. Enteropathogenic E. coli (EPEC) and Enterohemorrhagic E. coli (EHEC) were the major producers of ESBL and carbapenemase, respectively as indicated by serodiagnosis. They were further assessed for the presence of pathogenicity islands (PAIs) and phylogenetic background. The most predominant DEC PAI and ExPEC PAI were HPI and IICFT073. Most clinically ESBL-producers were group D and B2 while environmentally ones were group B1 and A. On contrary, clinically carbapenemase-producers belonged to group C and D. In conclusion, our study confirms the importance of phylogenetic group D, B2, and C origin for antibiotic resistance in E. coli. Ultimately, our findings support the fact that environmental isolates contribute to the local spread of E. coli pathogenicity in Egypt and these isolates maybe serve as reservoirs for transmission of resistance.
Archival bone marrow smears are useful in targeted next-generation sequencing for diagnosing myeloid neoplasms
Authors: Sadato Daichi , Hirama Chizuko , Kaiho-Soma Ai , Yamaguchi Ayaka , Kogure Hiroko , Takakuwa Sonomi , Ogawa Mina , Doki Noriko , Ohashi Kazuteru , Harada Hironori , Oboki Keisuke , Harada Yuka
Published: July 2021

Gene abnormalities, including mutations and fusions, are important determinants in the molecular diagnosis of myeloid neoplasms. The use of bone marrow (BM) smears as a source of DNA and RNA for next-generation sequencing (NGS) enables molecular diagnosis to be done with small amounts of bone marrow and is especially useful for patients without stocked cells, DNA or RNA. The present study aimed to analyze the quality of DNA and RNA derived from smear samples and the utility of NGS for diagnosing myeloid neoplasms. Targeted DNA sequencing using paired BM cells and smears yielded sequencing data of adequate quality for variant calling. The detected variants were analyzed using the bioinformatics approach to detect mutations reliably and increase sensitivity. Noise deriving from variants with extremely low variant allele frequency (VAF) was detected in smear sample data and removed by filtering. Consequently, various driver gene mutations were detected across a wide range of allele frequencies in patients with myeloid neoplasms. Moreover, targeted RNA sequencing successfully detected fusion genes using smear-derived, very low-quality RNA, even in a patient with a normal karyotype. These findings demonstrated that smear samples can be used for clinical molecular diagnosis with adequate noise-reduction methods even if the DNA and RNA quality is inferior.
Targeted capture sequencing identifies genetic variations of GRK4 and RDH8 in Han Chinese with essential hypertension in Xinjiang
Authors: Jiang Wenxi , Wang Xizi , Li Ronghui , Wang Panpan , Shan Guangle , Jia Xiaodong , Gu Mingliang
Published: July 2021

Essential hypertension is a common cardiovascular disease with complex etiology, closely related to genetic and environmental factors. The pathogenesis of hypertension involves alteration in vascular resistance caused by sympathetic nervous system (SNS) and renin angiotensin system (RAS). Susceptibility factors of hypertension vary with regions and ethnicities. In this study, we conducted target capture sequencing on 54 genes related to SNS and RAS derived from a collection of Han nationality, consisting of 151 hypertension patients and 65 normal subjects in Xinjiang, China. Six non-synonymous mutations related to hypertension were identified, including GRK4 rs1644731 and RDH8 rs1801058, Mutations are predicted to affect 3D conformation, force field, transmembrane domain and RNA secondary structure of corresponding genes. Based on protein interaction network and pathway enrichment, GRK4 is predicted to participate in hypertension by acting on dopaminergic synapse, together with interacting components. RDH8 is involved in vitamin A (retinol) metabolism and consequent biological processes related to hypertension. Thus, GRK4 and RDH8 may serve as susceptibility genes for hypertension. This finding provides new genetic evidence for elucidating risk factors of hypertension in Han nationality in Xinjiang, which in turn, enriches genetic resource bank of hypertension susceptibility genes.
Bunin's Plots in "Another Life" by Yuri Trifonov
Authors: Vladimirov Oleg
Published: July 2021

The article deals with the influence of Bunin's works on a novel by Trifonov "Another Life" («Другая жизнь»). In addition to direct and implicit reminiscences from verse and prose by Bunin, the plot of the story "Cold Autumn" («Холодная осень») is especially significant to the novel. The poem "What a cold Autumn!" («Какая холодная осень!») by Fet is a kind of a mediator between the two works, the first two lines of which are quoted in both writings by Bunin and Trifonov. The story and the novel correlated in terms of their theme, plot, composition and characters, are conceptually close in understanding the problem of "a person's private life and history". The correlation of the heroes' fates with epoch-making events taking place in these texts, as well as other concordances, bring us to the conclusion that the inclusion of Bunin's works supports Trifonov's concept of the world and the person – the uniqueness of individual human existence in the context of History. The writer, who like his hero Sergei Troitsky overcomes the formally ideological understanding of history, is attracted by Bunin's artistic experience of comprehension of memory, love, and nature metaphysics.
The Role of the Title in the Characterization of the Hero in G.I. Gazdanov’s Story "Black Swans"
Authors: Kukhtenkova Anastasia
Published: July 2021

The article deals with the role of the heading as a symbol in the characterization of the hero of the story by Gazdanov «Black Swans". The author of the article describes the actualization of the heading and the character's characteristics by taking into account the artistic psychologism. The frequency of repetition of the heading close to the end of the text is one of the individual style features of the writer's linguopoetics ("The Flight", "The Bombay", "The Iron Lord", etc.). There is a comparison between the vocabulary and text fields of the heading associative stimulus presented in the article. The psychological autobiography of the story hero is depicted by the textual interaction of the components of the heading. The black color corresponds to the refugee implication, suicide and uniqueness of the main character. The image of swans denotes Pavlov's longing for freedom, for the search of  illusions as an attempt to get rid of courageous loneliness, as well as his desire to unravel the existential mystery. The use of the syntactic lexeme "black swans" denotes the intertextual key message of the works by Gazdanov - that is "the inner journey", which is associated with the confessional narrative and the self-analysis of the hero-narrator
‘A Gentle Creature’ by Fyodor Dostoevsky: The Author As an Observer, an Interpreter and a Fantasist
Authors: Kovalev Oleg
Published: July 2021

Fyodor Dostoevsky's short story “A Gentle Creatureˮ, first published by the writer in 1876 as the November issue of his “Diary of a Writerˮ, is usually viewed in the context of the author's discourse on suicide contained in the previous issue of The “Diary of a Writerˮ, where the writer’s lot is described as an in-depth interpretation of life. At the same time, the theme of suicide is also brought up in connection with the overwhelming task of interpreting the event. However, the writer ultimately changed his writing strategy to produce “A Gentle Creatureˮ. Basing the story on an actual case of a suicide committed by a young woman amplified with autobiographical details, Dostoevsky develops a narrative model with complexity exceeding that of the original interpretation of the fact while in its essence being equivalent to the complexity of reality itself. The images of a straight line and a dot, employed by the author to interpret the event and the text of the short story, demonstrate that the author sees as a problem converting true-life information into a compressed narrative. Thus, in his short story “A Gentle Creatureˮ Dostoevsky offers the reader a model as complex as the life itself.
Was there Nevsky? Ideology and Poetics of V. M. Shukshin’s Story “Conversations under a Clear Moon”
Authors: Kulyapin Alexander
Published: July 2021

The article deals with the problematic issues and poetics of Shukshin’s story “Conversations under a Clear Moon”. Despite the fact that the title of the story contains the word “conversations”, there is no truly dialogical relations between the characters. The characters of the story, in fact, speak different languages. They need an interpreter, since they themselves do not understand interlocutor's speech well. The emergence of a language barrier between compatriots is natural. This is a consequence of the story’s character loss of identity: national, social and even gender. The writer focuses on the features of “non-Russianness” in the appearance, speeches, mentality of the main character - old man Baev. The process of losing national identity goes so far for Baev that he even puts forward an absurd hypothesis about his American origin. The interlocutor of Baev, Marya Selezneva, generally loses not only social, but also gender identity. The artistic world of the story “Conversations under a Clear Moon” is largely simulative. It is so illusory that the characters in the story cannot distinguish day from night, the moon from the sun. The line between (pseudo)life and death is practically erased in the story.