bluuebunny/crossref_metadata_2025 huggingface dataset:
scMethBank: a database for single-cell whole genome DNA methylation maps
Authors: Zong Wenting , Kang Hongen , Xiong Zhuang , Ma Yingke , Jin Tong , Gong Zheng , Yi Lizhi , Zhang Mochen , Wu Song , Wang Guoliang , Bao Yiming , Li Rujiao
Published: September 2021

Single-cell bisulfite sequencing methods are widely used to assess epigenomic heterogeneity in cell states. Over the past few years, large amounts of data have been generated and facilitated deeper understanding of the epigenetic regulation of many key biological processes including early embryonic development, cell differentiation and tumor progression. It is an urgent need to build a functional resource platform with the massive amount of data. Here, we present scMethBank, the first open access and comprehensive database dedicated to the collection, integration, analysis and visualization of single-cell DNA methylation data and metadata. Current release of scMethBank includes processed single-cell bisulfite sequencing data and curated metadata of 8328 samples derived from 15 public single-cell datasets, involving two species (human and mouse), 29 cell types and two diseases. In summary, scMethBank aims to assist researchers who are interested in cell heterogeneity to explore and utilize whole genome methylation data at single-cell level by providing browse, search, visualization, download functions and user-friendly online tools. The database is accessible at: https://ngdc.cncb.ac.cn/methbank/scm/.
A transcriptional complex of NGATHA and bHLH transcription factors directs stigma development in Arabidopsis
Authors: Ballester Patricia , Martínez-Godoy Maria A , Ezquerro Miguel , Navarrete-Gómez Marisa , Trigueros Marina , Rodríguez-Concepción Manuel , Ferrándiz Cristina
Published: September 2021

The stigma is an angiosperm-specific tissue that is essential for pollination. In the last two decades, several transcription factors with key roles in stigma development in Arabidopsis thaliana have been identified. However, genetic analyses have thus far been unable to unravel the precise regulatory interactions among these transcription factors or the molecular basis for their selective roles in different spatial and temporal domains. Here, we show that the NGATHA (NGA) and HECATE (HEC) transcription factors, which are involved in different developmental processes but are both essential for stigma development, require each other to perform this function. This relationship is likely mediated by their physical interaction in the apical gynoecium. NGA/HEC transcription factors subsequently upregulate INDEHISCENT (IND) and SPATULA and are indispensable for the binding of IND to some of its targets to allow stigma differentiation. Our findings support a nonhierarchical regulatory scenario in which the combinatorial action of different transcription factors provides exquisite temporal and spatial specificity of their developmental outputs.
The OsSPK1–OsRac1–RAI1 defense signaling pathway is shared by two distantly related NLR proteins in rice blast resistance
Authors: Yu Minxiang , Zhou Zhuangzhi , Liu Xue , Yin Dedong , Li Dayong , Zhao Xianfeng , Li Xiaobing , Li Shengping , Chen Renjie , Lu Ling , Yang Dewei , Tang Dingzhong , Zhu Lihuang
Published: September 2021

Resistance (R) proteins are important components of plant innate immunity. Most known R proteins are nucleotide-binding site leucine-rich repeat (NLR) proteins. Although a number of signaling components downstream of NLRs have been identified, we lack a general understanding of the signaling pathways. Here, we used the interaction between rice (Oryza sativa) and Magnaporthe oryzae to study signaling of rice NLRs in response to blast infection. We found that in blast resistance mediated by the NLR PIRICULARIA ORYZAE RESISTANCE IN DIGU 3 (PID3), the guanine nucleotide exchange factor OsSPK1 works downstream of PID3. OsSPK1 activates the small GTPase OsRac1, which in turn transduces the signal to the transcription factor RAC IMMUNITY1 (RAI1). Further investigation revealed that the three signaling components also play important roles in disease resistance mediated by the distantly related NLR protein Pi9, suggesting that the OsSPK1–OsRac1–RAI1 signaling pathway could be conserved across rice NLR-induced blast resistance. In addition, we observed changes in RAI1 levels during blast infection, which led to identification of OsRPT2a, a subunit of the 19S regulatory particle of the 26S proteasome. OsRPT2a seemed to be responsible for RAI1 turnover in a 26S proteasome-dependent manner. Collectively, our results suggest a defense signaling route that might be common to NLR proteins in response to blast infection.
Psychological Factors Change During the Rehabilitation of an Achilles Tendon Rupture: A Multicenter Prospective Cohort Study
Authors: Slagers Anton J , Dams Olivier C , van Zalinge Sara D , Geertzen Jan HB , Zwerver Johannes , Reininga Inge HF , van den Akker-Scheek Inge
Published: September 2021

Objective

The authors sought to gain insight into the changes in psychological factors during rehabilitation after Achilles tendon rupture (ATR) and to explore the association between psychological factors during rehabilitation and functional outcome 12 months after ATR.

Methods

Fifty patients clinically diagnosed with ATR were invited to visit the hospital 3, 6, and 12 months after injury for data collection. They completed questionnaires assessing psychological factors: psychological readiness to return to sport (Injury Psychological Readiness to Return to Sport Questionnaire); kinesiophobia (Tampa Scale for Kinesiophobia); expectations, motivation, and outcome measures related to symptoms and physical activity (Achilles Tendon Total Rupture Score); and sports participation and performance (Oslo Sports Trauma Research Centre Overuse Injury Questionnaire). To determine whether psychological factors changed over time, generalized estimating equation analyses were performed. Multivariate regression analyses were used to study the association between psychological factors at 3, 6, and 12 months and outcome measures at 12 months after ATR.

Results

Psychological readiness to return to sport improved, and kinesiophobia decreased significantly during rehabilitation. Psychological readiness at 6 and 12 months showed significant associations with sports participation and performance. Kinesiophobia at 6 months was significantly associated with symptoms and physical activity. Motivation remained high during rehabilitation and was highly associated with symptoms and physical activity, sports participation, and performance.

Conclusion

Psychological factors change during rehabilitation after ATR. Patients with lower motivation levels during rehabilitation, low psychological readiness to return to sports, and/or high levels of kinesiophobia at 6 months after ATR need to be identified.

Impact

According to these results, psychological factors can affect the rehabilitation of patients with ATR. Physical therapists can play an important role in recognizing patients with low motivation levels and low psychological readiness for return to sport and patients with high levels of kinesiophobia at 6 months post-ATR. Physical therapist interventions to enhance motivation and psychological readiness to return to sport and to reduce kinesiophobia need to be developed and studied in the post-ATR population.

Lay Summary

With Achilles tendon rupture, level of motivation, psychological readiness for return to sport, and fear of movement can affect rehabilitation outcome. A physical therapist can help recognize these factors.
Do peers share the same criteria for assessing grant applications?
Authors: Hug Sven E , Ochsner Michael
Published: September 2021

This study examines a basic assumption of peer review, namely, the idea that there is a consensus on evaluation criteria among peers, which is a necessary condition for the reliability of peer judgements. Empirical evidence indicating that there is no consensus or more than one consensus would offer an explanation for the disagreement effect, the low inter-rater reliability consistently observed in peer review. To investigate this basic assumption, we have surveyed all humanities scholars in Switzerland on 23 grant review criteria. We have employed latent class tree modelling to identify subgroups in which scholars rated criteria similarly (i.e. latent classes) and to explore covariates predicting class membership. We have identified two consensus classes, two consensus-close classes, and a consensus-far class. The consensus classes contain a core consensus (10 criteria related to knowledge gaps; feasibility; rigour; comprehensibility and argumentation; academic relevance; competence and experience of the applicant) and a broad consensus that include the core consensus plus eight contribution-related criteria, such as originality. These results provide a possible explanation for the disagreement effect. Moreover, the results are consistent with the notion of conservatism, which holds that original research is undervalued in peer review, while other aspects, such as methodology and feasibility, are overweighted. The covariate analysis indicated that age and having tenure increase from the consensus far to the consensus close to the consensus classes. This suggests that the more academic experience scholars accumulate, the more their understanding of review criteria conforms to the social norm.
Neotropical jewels in the moss: biodiversity, distribution and evolution of the genus Barbaria (Heterotardigrada: Echiniscidae)
Authors: Gąsiorek Piotr , Wilamowski Andrzej , Vončina Katarzyna , Michalczyk Łukasz
Published: September 2021

The genus Barbaria, recently established to accommodate the former Echiniscus bigranulatus group, is a tardigrade group emblematic for the South American tardigrade fauna. This unappendaged echiniscid lineage is widely recognized for the so-called ‘double’ sculpturing composed of endocuticular pillars and pseudopores or pores in the dorsal cuticle. The phylogenetic relationships in the genus have so far been completely unknown, but the discovery of two new species (B. paucigranulata sp. nov. and B. weglarskae sp. nov.), together with new genetic data for further six species (B. bigranulata, B. charrua comb. nov., B. danieli, B. jenningsi, B. madonnae and B. ollantaytamboensis), create an opportunity not only to uncover phyletic relationships, but also to reconstruct morphological evolution in the genus. To achieve this, we sequenced five genetic markers (18S rRNA, 28S rRNA, ITS1, ITS2, COI) for multiple populations of eight species of Barbaria (two-thirds of all known species) collected in Alabama (USA), Argentina and the Antarctic, and we analysed them in tandem with detailed morphological data. Our phylogentic analysis and the reconstruction of evolution of morphological traits suggests that the ancestor of the genus inhabited the Neotropics, and it was morphologically most similar to B. bigranulata. We also analyse literature records of Barbaria and conclude that the genus is most likely limited to the Neotropics, Antarctica and southern parts of the Nearctic. The findings are discussed in the context of the phylogeny of the Echiniscus evolutionary line.
Mitigating Drowsy Driving Risk for Night Shift Nurses
Authors: Geiger-Brown Jeanne , McDonald Anthony
Published: September 2021

Preventive measures range from napping to installing driver monitoring systems in cars.
Controversial Approval of New Drug to Treat Alzheimer's Disease
Authors: Aschenbrenner Diane S.
Published: September 2021

Aducanumab (Aduhelm), the first new drug to treat Alzheimer's disease since 2003, has received accelerated approval from the Food and Drug Administration (FDA).

This drug's approval has been highly contentious in the medical and scientific community owing to contradictory study findings and the FDA's advisory panel not recommending its approval.
More Adverse Events with Home Infusions
Authors: Rosenberg Karen
Published: September 2021

According to this study:

Patients with immune-mediated disease who received biologic infusions at home were more likely to be admitted to the ED or hospital that day or the next compared with patients who received infusions at a facility.

The safety implications of biologic home infusions need to be further evaluated.
Sugar-Sweetened Beverage Intake Linked to Early-Onset Colorectal Cancer Risk
Authors: Rosenberg Karen
Published: September 2021

According to this study:

Among women, a higher intake of sugar-sweetened beverages in adulthood and adolescence is associated with a substantially higher risk of early-onset colorectal cancer.

Reducing the intake of sugar-sweetened beverages in this population may reduce the incidence of early-onset colorectal cancer.
Transgender and Gender Diverse Nursing Care
Authors: Nye Caitlin Marie , Anderson Amanda
Published: September 2021

This column is designed to help new nurses in their first year at the bedside—a time of insecurity, growth, and constant challenges—and to offer advice as they learn what it means to be a nurse. Because content on the care of patients who are transgender and gender diverse (TGD) is largely missing from undergraduate nursing curricula, most nurses will learn to care for TGD patients when first working at the bedside. This article offers guidance on providing affirming care to TGD patients, including discussions of gender and pronouns, privacy considerations, and communication and advocacy.
A Case of Sudden Cardiac Arrest
Authors: Kupchik Nicole , Green Joel
Published: September 2021

Editor's note: This is the next installment in a series on electrocardiogram (ECG) interpretation. Nurses in all settings should know the basics, as medications and physiological changes can cause cardiac arrhythmias. Each article will start with a brief case scenario and an ECG strip and then take you step by step through analyzing the heart rhythm.
Aroused: A Rousing Look at Hormones
Authors: Brown Theresa
Published: September 2021

Stories of discovery, wrong turns, and hope.
Following the Lead
Authors: Gerber Lois
Published: September 2021

You can support a family member's treatment plan without taking charge.
Anemia in Pregnancy
Authors: Stanley Angela Y. , Wallace Jerrol B. , Hernandez Andrea M. , Spell Jenna L.
Published: September 2021

Screening recommendations for anemia during pregnancy, etiologies of inherited and noninherited forms of anemia, their impact on maternal–fetal outcomes, and the clinical management of pregnant patients presenting with these conditions are reviewed. Anemia during pregnancy can cause adverse perinatal outcomes including preterm labor, premature rupture of membranes, and increased maternal and fetal mortality. Physiologic (dilutional) anemia and iron deficiency anemia are the two most common noninherited forms of anemia, and some cases may be the result of an underlying comorbidity such as diabetes or lupus. Aplastic anemia and autoimmune hemolytic anemia are uncommon forms of noninherited anemias that also merit discussion. Inherited forms of anemia include sickle cell disease, alpha-thalassemia, and beta-thalassemia. Timely diagnosis and treatment of anemia during pregnancy, whether inherited or noninherited, is imperative to protect mother and baby from potential adverse outcomes associated with these conditions.
Use of Lean Healthcare to Improve Hospital Throughput and Reduce LOS
Authors: Mangum Christopher D. , Andam-Mejia Rachel L. , Hale Leslie R. , Mananquil Ana , Fulcher Kyle R. , Hall Jason L. , McDonald Laura Anne C. , Sjogren Karl N. , Villalon Felicita D. , Mehta Ami , Shomaker Kyrie , Johnson Edward A. , Godambe Sandip A.
Published: September 2021

Introduction:

Improving the discharge process is an area of focus throughout healthcare organizations. Capacity constraints, efficiency improvement, patient safety, and quality care are driving forces for many discharge process workgroups.

Methods:

Following the Pareto principle, we focused on improving the discharge process on the medical-surgical units that received the most patients admitted from the emergency department. Increased demand for medical-surgical beds, renovations, and diminished bed capacity made it imperative to improve efficiency using quality improvement techniques. A core team of frontline staff decreased the time between computer entry of discharge orders and patient’s departure from the unit to less than 60 minutes, with 80% compliance. The team developed a daily dashboard that detailed the process and outcome measures to create situational awareness and daily visual management. Additional observations of staff workflow uncovered excessive walking for printer use. Printers were placed at the point of use to reduce transport times. Next, using survey results provided by patients on discharge quality, a Treasure Map that aided with teach-back and Team Discharge were implemented to level the staff’s workload. Finally, physicians discharged patients earlier in the day. They standardized their discharge criteria to remove subjectivity from the discharge process and enable better team involvement.

Results:

After implementing 4 interventions, the average time between computer entry of discharge orders and patient’s departure from the unit decreased (94.26 versus 65.98 minutes; P < 0.001), simultaneously reducing our average length of stay from 5.62 to 4.81 days (P < 0.001).

Conclusions:

In conclusion, hardwiring proven interventions and complementing them with daily visual management led to significant, sustained results.
Outcomes following out-of-hours acute cholecystectomy: A systematic review and meta-analysis
Authors: Bhat Sameer , Varghese Chris , Xu William , Barazanchi Ahmed W.H. , Ratnayake Bathiya , O’Grady Gregory , Windsor John A. , Wells Cameron I.
Published: September 2021

BACKGROUND

Cholecystectomy is one of the most commonly performed abdominal operations. Rising demands on acute operating theater availability and resource utilization in the daytime have led to acute cholecystectomy being performed out-of-hours (in the evenings, at night, or on weekends), although it remains unknown whether outcomes differ between out-of-hours and in-hours (during the daytime on weekdays) acute cholecystectomy. This systematic review and meta-analysis aimed to compare outcomes following out-of-hours versus in-hours acute cholecystectomy.

METHODS

The study protocol was prospectively registered on PROSPERO (ID: CRD42021226127). MEDLINE, EMBASE, and Scopus databases were systematically searched for studies comparing outcomes following out-of-hours and in-hours acute cholecystectomy in adults with any acute benign gallbladder disease. The outcomes of interest were rates of bile leakage, bile duct injury, overall postoperative complications, conversion to open cholecystectomy, specific intraoperative and postoperative complications, length of stay, readmission, and mortality. Subgroup (evening/night-time vs. daytime, weekend vs. weekday, acute surgical unit [ASU]-only, non-ASU, and laparoscopic-only) and sensitivity analyses of adjusted multivariate regression analysis results was also performed.

RESULTS

Eleven studies were included. There were no differences between out-of-hours and in-hours acute cholecystectomy for rates of bile leakage, bile duct injury, overall postoperative complications, conversion to open cholecystectomy, operative duration, readmission, mortality, and postoperative length of stay. Higher rates of postoperative sepsis (odds ratio, 1.58; 95% confidence interval, 1.04–2.41; p = 0.03) and pneumonia (odds ratio, 1.55; 95% confidence interval, 1.06–2.26; p = 0.02) were observed following out-of-hours acute cholecystectomy on univariate meta-analysis, but not after the adjusted multivariate meta-analysis. Higher conversion rates were observed when out-of-hours cholecystectomy was performed in centers without an ASU.

CONCLUSION

This systematic review and meta-analysis has not shown an increased risk in overall or specific complications associated with out-of-hours compared with in-hours acute cholecystectomy. However, future studies should assess the potential impact of structural hospital factors, such as an ASU, on outcomes following out-of-hours acute cholecystectomy.

LEVEL OF EVIDENCE

Systematic Review and Meta-Analysis Study, Level IV.
Improving mortality in older adult trauma patients: Are we doing better?
Authors: Karam Basil S. , Patnaik Rohan , Murphy Patrick , deRoon-Cassini Terri A. , Trevino Colleen , Hemmila Mark R. , Haines Krista , Puzio Thaddeus J. , Charles Anthony , Tignanelli Christopher , Morris Rachel
Published: September 2021

BACKGROUND

Older adult trauma is associated with high morbidity and mortality. Individuals older than 65 years are expected to make up more than 21% of the total population and almost 39% of trauma admissions by 2050. Our objective was to perform a national review of older adult trauma mortality and identify associated risk factors to highlight potential areas for improvement in quality of care.

MATERIALS AND METHODS

This is a retrospective cohort study of the National Trauma Data Bank including all patients age ≥65 years with at least one International Classification of Diseases, Ninth Revision, Clinical Modification trauma code admitted to a Level I or II US trauma center between 2007 and 2015. Variables examined included demographics, comorbidities, emergency department vitals, injury characteristics, and trauma center characteristics. Multilevel mixed-effect logistic regression was performed to identify independent risk factors of in-hospital mortality.

RESULTS

There were 1,492,759 patients included in this study. The number of older adult trauma patients increased from 88,056 in 2007 to 158,929 in 2015 (p > 0.001). Adjusted in-hospital mortality decreased in 2014 to 2015 (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.86–0.91) when compared with 2007 to 2009. Admission to a university hospital was protective (OR, 0.83; 95% CI, 0.74–0.93) as compared with a community hospital admission. There was no difference in mortality risk between Level II and Level I admission (OR, 1.00; 95% CI, 0.92–1.08). The strongest trauma-related risk factor for in-patient mortality was pancreas/bowel injury (OR, 2.25; 95% CI, 2.04–2.49).

CONCLUSION

Mortality in older trauma patients is decreasing over time, indicating an improvement in the quality of trauma care. The outcomes of university based hospitals can be used as national benchmarks to guide quality metrics.

LEVEL OF EVIDENCE

Therapeutic/Care Management, Level IV.
Developing a national trauma research action plan: Results from the Burn Research Gap Delphi Survey
Authors: Gibran Nicole S. , Shipper Edward , Phuong Jimmy , Braverman Max , Bixby Pam , Price Michelle A. , Bulger Eileen M. ,   on behalf of the NTRAP Burns & Reconstructive Surgery Panel Group
Published: September 2021

BACKGROUND

The 2016 National Academies of Science, Engineering and Medicine call for a national integrated, military-civilian trauma action plan to achieve zero preventable deaths and disability after injury included a proposal to establish a National Trauma Research Action Plan to “strengthen trauma research and ensure that the resources available for this research are commensurate with the importance of injury and the potential for improvement in patient outcomes.” The Department of Defense funded the Coalition for National Trauma Research to generate a comprehensive research agenda spanning the continuum of trauma/burn care from prehospital to rehabilitation. The Burn/Reconstructive Surgery group represents one focus area for this research agenda development.

METHODS

Experts in burn and reconstructive surgery research identified gaps in knowledge, generated research questions and prioritized questions using a consensus driven Delphi survey approach. Participants were identified using established Delphi recruitment guidelines to ensure heterogeneity and generalizability with military and civilian representatives. Literature reviews informed the panel. Panelists were encouraged to use a PICO format to generate research questions: Patient/Population; Intervention; Compare/Control; Outcome. Participants ranked the priority of each question on a nine-point Likert scale, which was categorized to represent low, medium, and high priority items. Consensus was defined based on ≥60% panelist agreement.

RESULTS

Subject matter experts generated 949 research questions in 29 Burn & 26 Reconstruction topics. Five hundred ninety-seven questions reached consensus. Of these, 338 (57%) were high-priority, 180 (30%), medium-priority, and 78 (13%) low-priority questions.

CONCLUSION

Many high-priority questions translate to complex wound management and outcomes. Panel recognition that significant gaps in knowledge exist in understanding functional outcomes after injury underscores the importance of long-term recovery metrics even when studying acute injury or interventions such as resuscitation or inhalation injury. Funding agencies and burn/reconstructive surgery researchers should consider these gaps when they prioritize future research.

LEVEL OF EVIDENCE

Expert consensus, Level IV.
The derivation of an International Classification of Diseases, Tenth Revision–based trauma-related mortality model using machine learning
Authors: Tran Zachary , Zhang Wenhao , Verma Arjun , Cook Alan , Kim Dennis , Burruss Sigrid , Ramezani Ramin , Benharash Peyman
Published: September 2021

BACKGROUND

Existing mortality prediction models have attempted to quantify injury burden following trauma-related admissions with the most notable being the Injury Severity Score (ISS). Although easy to calculate, it requires additional administrative coding. International Classification of Diseases (ICD)–based models such as the Trauma Mortality Prediction Model (TMPM-ICD10) circumvent these limitations, but they use linear modeling, which may not adequately capture the intricate relationships of injuries on mortality. Using ICD-10 coding and machine learning (ML) algorithms, the present study used the National Trauma Data Bank to develop mortality prediction models whose performance was compared with logistic regression, ISS, and TMPM-ICD10.

METHODS

The 2015 to 2017 National Trauma Data Bank was used to identify adults following trauma-related admissions. Of 8,021 ICD-10 codes, injuries were categorized into 1,495 unique variables. The primary outcome was in-hospital mortality. eXtreme Gradient Boosting (XGBoost), a ML technique that uses iterations of decision trees, was used to develop mortality models. Model discrimination was compared with logistic regression, ISS, and TMPM-ICD10 using receiver operating characteristic curve and probabilistic accuracy with calibration curves.

RESULTS

Of 1,611,063 patients, 54,870 (3.41%) experienced in-hospital mortality. Compared with those who survived, those who died more frequently suffered from penetrating trauma and had a greater number of injuries. The XGBoost model exhibited superior receiver operating characteristic curve (0.863 [95% confidence interval (CI), 0.862–0.864]) compared with logistic regression (0.845 [95% CI, 0.844–0.846]), ISS (0.828 [95% CI, 0.827–0.829]), and TMPM-ICD10 (0.861 [95% CI, 0.860–0.862]) (all p < 0.001). Importantly, the ML model also had significantly improved calibration compared with other methodologies (XGBoost, coefficient of determination (R
2) = 0.993; logistic regression, R
2 = 0.981; ISS, R
2 = 0.649; TMPM-ICD10, R
2 = 0.830).

CONCLUSION

Machine learning models using XGBoost demonstrated superior performance and calibration compared with logistic regression, ISS, and TMPM-ICD10. Such approaches in quantifying injury severity may improve its utility in mortality prognostication, quality improvement, and trauma research.

LEVEL OF EVIDENCE

Prognostic and Epidemiologic; level III.
Reconstituting the genus Mycobacterium
Authors: Meehan Conor J. , Barco Roman A. , Loh Yong-Hwee E. , Cogneau Sari , Rigouts Leen
Published: September 2021

The definition of a genus has wide-ranging implications both in terms of binomial species names and also evolutionary relationships. In recent years, the definition of the genus

Mycobacterium

has been debated due to the proposed split of this genus into five new genera (

Mycolicibacterium

,

Mycolicibacter

,

Mycolicibacillus

,

Mycobacteroides

and an emended

Mycobacterium

). Since this group of species contains many important obligate and opportunistic pathogens, it is important that any renaming of species does not cause confusion in clinical treatment as outlined by the nomen periculosum rule (56a) of the Prokaryotic Code. In this study, we evaluated the proposed and original genus boundaries for the mycobacteria, to determine if the split into five genera was warranted. By combining multiple approaches for defining genus boundaries (16S rRNA gene similarity, amino acid identity index, average nucleotide identity, alignment fraction and percentage of conserved proteins) we show that the original genus

Mycobacterium

is strongly supported over the proposed five-way split. Thus, we propose that the original genus label be reapplied to all species within this group, with the proposed five genera potentially used as sub-genus complex names.
Natural antimicrobial peptides as a source of new antiviral agents
Authors: Zakaryan Hovakim , Chilingaryan Garri , Arabyan Erik , Serobian Andre , Wang Guangshun
Published: September 2021

Current antiviral drugs are limited because of their adverse side effects and increased rate of resistance. In recent decades, much scientific effort has been invested in the discovery of new synthetic and natural compounds with promising antiviral properties. Among this new generation of compounds, antimicrobial peptides with antiviral activity have been described and are attracting attention due to their mechanism of action and biological properties. To understand the potential of antiviral peptides (AVPs), we analyse the antiviral activity of well-known AVP families isolated from different natural sources, discuss their physical–chemical properties, and demonstrate how AVP databases can guide us to design synthetic AVPs with better therapeutic properties. All considerations in this sphere of antiviral therapy clearly demonstrate the remarkable contribution that AVPs may make in conquering old as well as newly emerging viruses that plague humanity.
Karawun: assisting evaluation of advances in multimodal imaging for neurosurgical planning and intraoperative neuronavigation
Authors: Beare Richard , Alexander Bonnie , Warren Aaron , Kean Michael , Seal Marc , Wray Alison , Maixner Wirginia , Yang Joseph Yuan-Mou
Published: September 2021

Submitted toMagnetic Resonance in Medicine

Purpose

To introduce a tool allowing neurosurgeons to evaluate the results of research tractography workflows for presurgical planning and intraoperative image-guidance, using standard neurosurgical navigation platforms.

Theory and Methods

Improving communication between neurosurgeons and researchers developing new image acquisition and processing methods is critical for rapid translation of research to surgical practice. Presenting research outputs within existing clinical workflows is one approach that can assist such interdisciplinary communication. Neurosurgical navigation platforms can display and manipulate a wide range of medical image data and associated delineations and thus allow clinicians to evaluate the impact of new imaging research on their work. Currently, it is extremely difficult to integrate research-based image processing outputs into standard neurosurgical navigation platforms.

Results

In this note we introduceKarawun, an open-source software tool for converting outputs from research imaging pipelines, especially diffusion MRI tractography reconstructions using advanced methodologies currently unavailable on commercial navigation platforms, into forms that can be imported into theBrainlabneurosurgical navigation platform (Brainlab AG, Munich, Germany). The externally created tractography images and delineations can be viewed and manipulated as if they were created byBrainlab. We illustrate how two surgical workups, created using open-source tools and different processing choices can be presented to the neurosurgeon who can evaluate the impact of the differences between the two workups on surgical decisions.

Conclusion

Karawunallows researchers developing novel imaging methodologies to display their results in environments that are familiar to clinical end-users, especially neurosurgeons, thus assisting translation of research into clinical practice.
Two doses of the mRNA BNT162b2 vaccine reduce severe outcomes, viral load and secondary attack rate: evidence from a SARS-CoV-2 Alpha outbreak in a nursing home in Germany, January-March 2021
Authors: Meyer Emily Dorothee , Sandfort Mirco , Bender Jennifer , Matysiak-Klose Dorothea , Dörre Achim , Bojara Gerhard , Beyrer Konrad , Hellenbrand Wiebke
Published: September 2021

A SARS-CoV-2 Alpha outbreak was detected in a nursing home after residents and staff had completed vaccination with BNT162b. In a retrospective cohort study, we estimated an age-adjusted vaccine effectiveness of 88% [95% confidence interval (95%CI) 41-98%] against hospitalization/death. Ct values at diagnosis were higher with longer intervals since the second vaccination [>21 vs. ≤21 days: 4.82 cycles, 95%CI: 0.06-9.58]. Secondary attack rates were 67% lower in households of vaccinated [2/9 (22.2%)] than unvaccinated infected staff [12/18 (66.7%); p=0.046]. Vaccination reduced the risk of severe outcomes, Ct values and transmission, but not fully. Non-pharmaceutical interventions remain important for vaccinated individuals.
Subtyping of common complex diseases and disorders by integrating heterogeneous data. Identifying clusters among women with lower urinary tract symptoms in the LURN study
Authors: Andreev Victor P. , Helmuth Margaret E. , Liu Gang , Smith Abigail R. , Merion Robert M. , Yang Claire C. , Cameron Anne P. , Jelovsek J. Eric , Amundsen Cindy L. , Helfand Brian T. , Bradley Catherine S. , DeLancey John O. L. , Griffith James W. , Glaser Alexander P. , Gillespie Brenda W. , Clemens J. Quentin , Lai H. Henry ,   the LURN Study Group
Published: September 2021

We present a novel methodology for subtyping of persons with a common clinical symptom complex by integrating heterogeneous continuous and categorical data. We illustrate it by clustering women with lower urinary tract symptoms (LUTS), who represent a heterogeneous cohort with overlapping symptoms and multifactorial etiology. Identifying subtypes within this group would potentially lead to better diagnosis and treatment decision-making. Data collected in the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN), a multi-center prospective observational cohort study, included self-reported urinary and non-urinary symptoms, bladder diaries, and physical examination data for 545 women. Heterogeneity in these multidimensional data required thorough and non-trivial preprocessing, including scaling by controls and weighting to mitigate data redundancy, while the various data types (continuous and categorical) required novel methodology using a weighted Tanimoto indices approach. Data domains only available on a subset of the cohort were integrated using a semi-supervised clustering approach. Novel contrast criterion for determination of the optimal number of clusters in consensus clustering was introduced and compared with existing criteria. Distinctiveness of the clusters was confirmed by using multiple criteria for cluster quality, and by testing for significantly different variables in pairwise comparisons of the clusters. Cluster dynamics were explored by analyzing longitudinal data at 3- and 12-month follow-up. Five distinct clusters of women with LUTS were identified using the developed methodology. The clinical relevance of the identified clusters is discussed and compared with the current conventional approaches to the evaluation of LUTS patients. Rationale and thought process are described for selection of procedures for data preprocessing, clustering, and cluster evaluation. Suggestions are provided for minimum reporting requirements in publications utilizing clustering methodology with multiple heterogeneous data domains.
Concerted changes in the pediatric single-cell intestinal ecosystem before and after anti-TNF blockade
Authors: Zheng Hengqi Betty , Doran Benjamin A. , Kimler Kyle , Yu Alison , Tkachev Victor , Niederlova Veronika , Cribbin Kayla , Fleming Ryan , Bratrude Brandi , Betz Kayla , Cagnin Lorenzo , McGuckin Connor , Keskula Paula , Albanese Alexandre , Sacta Maria , de Sousa Casal Joshua , van Esch Ruben , Kwong Andrew C. , Kummerlowe Conner , Taliaferro Faith , Fiaschi Nathalie , Kou Baijun , Coetzee Sandra , Jalal Sumreen , Yabe Yoko , Dobosz Michael , Wipperman Matthew F. , Hamon Sara , Kalliolias George D. , Hooper Andrea , Lim Wei Keat , Haxhinasto Sokol , Wei Yi , Ford Madeline , Ambartsumyan Lusine , Suskind David L. , Lee Dale , Deutsch Gail , Deng Xuemei , Collen Lauren V. , Mitsialis Vanessa , Snapper Scott B. , Wahbeh Ghassan , Shalek Alex K. , Ordovas-Montanes Jose , Kean Leslie S.
Published: September 2021

Crohn’s disease is an inflammatory bowel disease (IBD) commonly treated through anti-TNF blockade. However, most patients still relapse and inevitably progress. Comprehensive single-cell RNA-sequencing (scRNA-seq) atlases have largely sampled patients with established treatment-refractory IBD, limiting our understanding of which cell types, subsets, and states at diagnosis anticipate disease severity and response to treatment. Here, through combining clinical, flow cytometry, histology, and scRNA-seq methods, we profile diagnostic human biopsies from the terminal ileum of treatment-naïve pediatric patients with Crohn’s disease (pediCD; n=14), matched repeat biopsies (pediCD-treated; n=8) and from non-inflamed pediatric controls with functional gastrointestinal disorders (FGID; n=13). To resolve and annotate epithelial, stromal, and immune cell states among the 201,883 baseline single-cell transcriptomes, we develop a principled and unbiased tiered clustering approach, ARBOL. Through flow cytometry and scRNA-seq, we observe that treatment-naïve pediCD and FGID have similar broad cell type composition. However, through high-resolution scRNA-seq analysis and microscopy, we identify significant differences in cell subsets and states that arise during pediCD relative to FGID. By closely linking our scRNA-seq analysis with clinical meta-data, we resolve a vector of T cell, innate lymphocyte, myeloid, and epithelial cell states in treatment-naïve pediCD (pediCD-TIME) samples which can distinguish patients along the trajectory of disease severity and anti-TNF response. By using ARBOL with integration, we position repeat on-treatment biopsies from our patients between treatment-naïve pediCD and on-treatment adult CD. We identify that anti-TNF treatment pushes the pediatric cellular ecosystem towards an adult, more treatment-refractory state. Our study jointly leverages a treatment-naïve cohort, high-resolution principled scRNA-seq data analysis, and clinical outcomes to understand which baseline cell states may predict Crohn’s disease trajectory.
Unusual SARS-CoV-2 intra-host diversity reveals lineages superinfection
Authors: Dezordi Filipe Zimmer , Resende Paola Cristina , Naveca Felipe Gomes , do Nascimento Valdinete Alves , de Souza Victor Costa , Paixão Anna Carolina Dias , Appolinario Luciana , Lopes Renata Serrano , Mendonça Ana Carolina da Fonseca , da Rocha Alice Sampaio Barreto , Venas Taina Moreira Martins , Pereira Elisa Cavalcante , Salvato Richard Steiner , Gregianini Tatiana Schäffer , Martins Leticia Garay , Pereira Felicidade Mota , Rovaris Darcita Buerger , Fernandes Sandra Bianchini , Ribeiro-Rodrigues Rodrigo , Costa Thais Oliveira , Sousa Joaquim Cesar , Miyajima Fabio , Delatorre Edson , Gräf Tiago , Bello Gonzalo , Siqueira Marilda Mendonça , Wallau Gabriel da Luz
Published: September 2021

The SARS-CoV-2 has infected almost 200 million people worldwide by July 2021 and the pandemic has been characterized by infection waves of viral lineages showing distinct fitness profiles. The simultaneous infection of a single individual by two distinct SARS-CoV-2 lineages provides a window of opportunity for viral recombination and the emergence of new lineages with differential phenotype. Several hundred SARS-CoV-2 lineages are currently well characterized but two main factors have precluded major coinfection/codetection analysis thus far: i) the low diversity of SARS-CoV-2 lineages during the first year of the pandemic which limited the identification of lineage defining mutations necessary to distinguish coinfecting viral lineages; and the ii) limited availability of raw sequencing data where abundance and distribution of intrasample/intrahost variability can be accessed. Here, we have put together a large sequencing dataset from Brazilian samples covering a period of 18 May 2020 to 30 April 2021 and probed it for unexpected patterns of high intrasample/intrahost variability. It enabled us to detect nine cases of SARS-CoV-2 coinfection with well characterized lineage-defining mutations. In addition, we matched these SARS-CoV-2 coinfections with spatio-temporal epidemiological data confirming their plausibility with the co-circulating lineages at the timeframe investigated. These coinfections represent around 0.61% of all samples investigated. Although our data suggests that coinfection with distinct SARS-CoV-2 lineages is a rare phenomenon, it is likely an underestimation and coinfection rates warrants further investigation.

DATA SUMMARY

The raw fastq data of codetection cases are deposited on gisaid.org and correlated to gisaid codes: EPI_ISL_1068258, EPI_ISL_2491769, EPI_ISL_2491781, EPI_ISL_2645599, EPI_ISL_2661789, EPI_ISL_2661931, EPI_ISL_2677092, EPI_ISL_2777552, EPI_ISL_3869215. Supplementary data are available on https://doi.org/10.6084/m9.figshare.16570602.v1. The workflow code used in this study is publicly available on: https://github.com/dezordi/IAM_SARSCOV2.
Understanding the pathways leading to socioeconomic inequalities in HIV testing uptake in 18 sub-Saharan African countries: a mediation analysis
Authors: Ante-Testard Pearl Anne , Hamidouche Mohamed , Apouey Bénédicte , Baggaley Rachel , Larmarange Joseph , Benmarhnia Tarik , Temime Laura , Jean Kévin
Published: September 2021

Introduction

Although socioeconomic inequalities in HIV prevention, testing and treatment services have been well documented, their drivers remain poorly understood. Understanding the different pathways between socioeconomic position and HIV testing across different countries could help designing tailored programs aimed at reducing such inequalities.

Methods

We analysed data from Demographic and Health Surveys conducted between 2010 and 2018 in 18 sub-Saharan African countries (Burkina Faso, Cameroon, Côte d’Ivoire, Congo DR, Ethiopia, Guinea, Kenya, Lesotho, Liberia, Malawi, Mali, Niger, Rwanda, Senegal, Sierra Leone, Tanzania, Zambia and Zimbabwe). Using a potential outcomes framework and the product method, we decomposed the total effect linking wealth and recent (< 12 months) HIV testing into i) direct effects, and ii) indirect effects, via demand-related (related to individual’s ability to perceive need for care and inclination to seek care) or supply-related (related to individual’s ability to reach, pay for and engage in health care) mediators. Multivariable gender-specific modified Poisson models were fitted to estimate proportions mediated, while accounting for exposure-mediator interaction when present.

Results

A total of 392,044 participants were included in the analysis. Pro-rich wealth-related inequalities were observed in a majority of countries, with nine countries with high levels of inequalities among women and 15 countries among men.

The indirect effects of each mediator varied greatly across countries. The proportion mediated tended to be higher for demand-related than for supply-related mediators. For instance, among women, HIV-related knowledge was estimated to mediate up to 12.1% of inequalities in Côte d’Ivoire; this proportion was up to 31.5% for positive attitudes toward people living with HIV (PLHIV) in Senegal. For the four supply-related mediators, the proportion mediated was systematically below 7%. Similar conclusions were found when repeating analyses on men for the demand-related mediators, with higher proportions mediated by positive attitudes toward PLHIV (up to 39.9% in Senegal).

Conclusions

Our findings suggest that socioeconomic inequalities in HIV testing may be mediated by the demand-side more than supply-side characteristics, with important variability across countries. Overall, the important inter-country heterogeneity in pathways of socioeconomic inequalities in HIV testing illustrates that addressing inequalities requires tailored efforts as well as upstream interventions.

A French version of the abstract is available upon request from the corresponding author.
Detection of COVID-19 in smartphone-based breathing recordings using CNN-BiLSTM: a pre-screening deep learning tool
Authors: Alkhodari Mohanad , Khandoker Ahsan H.
Published: September 2021

This study was sought to investigate the feasibility of using smartphone-based breathing sounds within a deep learning framework to discriminate between COVID-19, including asymptomatic, and healthy subjects. A total of 480 breathing sounds (240 shallow and 240 deep) were obtained from a publicly available database named Coswara. These sounds were recorded by 120 COVID-19 and 120 healthy subjects via a smartphone microphone through a website application. A deep learning framework was proposed herein the relies on hand-crafted features extracted from the original recordings and from the mel-frequency cepstral coefficients (MFCC) as well as deep-activated features learned by a combination of convolutional neural network and bi-directional long short-term memory units (CNN-BiLSTM). Analysis of the normal distribution of the combined MFCC values showed that COVID-19 subjects tended to have a distribution that is skewed more towards the right side of the zero mean (shallow: 0.59±1.74, deep: 0.65±4.35). In addition, the proposed deep learning approach had an overall discrimination accuracy of 94.58% and 92.08% using shallow and deep recordings, respectively. Furthermore, it detected COVID-19 subjects successfully with a maximum sensitivity of 94.21%, specificity of 94.96%, and area under the receiver operating characteristic (AUROC) curves of 0.90. Among the 120 COVID-19 participants, asymptomatic subjects (18 subjects) were successfully detected with 100.00% accuracy using shallow recordings and 88.89% using deep recordings. This study paves the way towards utilizing smartphone-based breathing sounds for the purpose of COVID-19 detection. The observations found in this study were promising to suggest deep learning and smartphone-based breathing sounds as an effective pre-screening tool for COVID-19 alongside the current reverse-transcription polymerase chain reaction (RT-PCR) assay. It can be considered as an early, rapid, easily distributed, time-efficient, and almost no-cost diagnosis technique complying with social distancing restrictions during COVID-19 pandemic.