bluuebunny/crossref_metadata_2025 huggingface dataset:
First-time Glenohumeral Dislocations: Current Evidence and Considerations in Clinical Decision Making
Authors: Kunze Kyle N. , Cohn Matthew R. , Williams Brady T. , Garrigues Grant , Chahla Jorge
Published: November 2020

The decision to manage first-time shoulder dislocations conservatively or operatively has become increasingly complex because of conflicting literature. Although shoulder dislocations have traditionally been managed with reduction and immobilization, recent evidence has suggested high rates of subsequent recurrence. Surgical intervention is thought to better restore stability and decrease recurrence rates; however, it also has the potential for additional morbidity and financial cost. As such, recent literature has sought to better define patient risk profiles to identify optimal candidates for both conservative and operative management. The purpose of the current review is to provide a comprehensive and evidence-based assessment of the most recent literature to better delineate an appropriate treatment algorithm for this challenging clinical scenario.
Health-Related Quality of Life After Community-Acquired Septic Shock in Children With Preexisting Severe Developmental Disabilities
Authors: Meert Kathleen L. , Reeder Ron W. , Maddux Aline B. , Banks Russell , Berg Robert A. , Newth Christopher J. , Hall Mark W. , Quasney Michael , Carcillo Joseph A. , McQuillen Patrick S. , Mourani Peter M. , Chima Ranjit S. , Holubkov Richard , Sorenson Samuel , McGalliard Julie , Dean J. Michael , Zimmerman Jerry J.
Published: November 2020

OBJECTIVES:

To serially evaluate health-related quality of life during the first year after community-acquired septic shock in children with preexisting severe developmental disabilities and explore factors associated with health-related quality of life changes in these children.

DESIGN:

Secondary analysis of the Life after Pediatric Sepsis Evaluation investigation.

SETTING:

Twelve academic PICU in the United States.

PATIENTS:

Children greater than or equal to 1 month and less than 18 years old identified by their family caregiver (e.g., parent/guardian) as having severe developmental disability prior to septic shock.

INTERVENTIONS:

Family caregivers completed the Stein-Jessop Functional Status II-R Short Form as a measure of their child’s health-related quality of life at baseline (reflecting preadmission status), day 7, and months 1, 3, 6, and 12 following PICU admission. Stein-Jessop Functional Status II-R Short Form scores were linearly transformed to a 0–100 scale, with higher scores indicating better health-related quality of life.

MEASUREMENTS AND MAIN RESULTS:

Of 392 Life after Pediatric Sepsis Evaluation participants, 137 were identified by their caregiver as having a severe developmental disability. Sixteen children (11.6%) with severe disability died during the 12 months following septic shock. Among 121 survivors, Stein-Jessop Functional Status II-R Short Form scores declined from preadmission baseline to day 7 (70.7 ± 16.1 vs 55.6 ± 19.2; p < 0.001). Stein-Jessop Functional Status II-R Short Form scores remained below baseline through month 12 (59.1 ± 21.0, p < 0.001 vs baseline). After adjusting for baseline Stein-Jessop Functional Status II-R Short Form, the caregiver being a single parent/guardian was associated with lower month 3 Stein-Jessop Functional Status II-R Short Form scores (p = 0.041). No other baseline child or caregiver characteristic, or critical illness-related factors were significantly associated with month 3 Stein-Jessop Functional Status II-R Short Form scores.

CONCLUSIONS:

Health-related quality of life among children with severe developmental disability remains, on average, below baseline during the first year following community-acquired septic shock. Children with severe disability and septic shock that are in single parent families are at increased risk. Clinical awareness of the potential for decline in health-related quality of life among disabled children is essential to prevent this adverse outcome from being missed.
Facial Aging: A Quantitative Analysis of Midface Volume Changes over 11 Years
Authors: Boehm Lucas M. , Morgan Aaron , Hettinger Patrick , Matloub Hani S.
Published: November 2020

Background:

Anatomical studies have identified separate superficial and deep facial fat compartments, leading some to theorize that volume loss from the deep midface causes overlying superficial fat pseudoptosis. Unfortunately, a paucity of evidence exists regarding whether facial fat volume is truly lost with age and, if so, whether it is lost equally or differentially from the superficial and deep compartments. The aim of this study was to quantify volume changes occurring with age within the superficial, deep, and buccal fat compartments of the midface.

Methods:

A retrospective longitudinal study was performed evaluating individuals aged 30 to 65 years who underwent facial computed tomography followed by facial computed tomography greater than or equal to 10 years later. Superficial midface, deep midface, and buccal fat volumes were quantified using Horos radiology software.

Results:

Nineteen subjects met inclusion criteria. Mean total fat volume decreased significantly from 46.47 cc to 40.81 cc (p < 0.01). The mean superficial and deep fat volumes both decreased significantly from 26.10 cc to 23.15 cc (p < 0.01) and from 11.01 cc to 8.98 cc (p < 0.01), respectively. No significant difference was observed in buccal fat volume over time (9.36 cc to 8.68 cc; p = 0.04). Patients lost an average of 11.3 percent of their initial superficial fat volume and 18.4 percent of their initial deep fat volume.

Conclusions:

Significant volume loss was observed from both superficial and deep facial fat compartments over a mean 11.3 years. Patients lost a greater percentage of deep facial fat volume, providing support for the theory of pseudoptosis caused by deep midface fat loss.
The Role of Magnetic Resonance Imaging in (Future) Cancer Staging
Authors: Scheenen Tom W.J. , Zamecnik Patrik
Published: November 2020

The presence or absence of lymph node metastases is a very important prognostic factor in patients with solid tumors. Current invasive and noninvasive diagnostic methods for N-staging like lymph node dissection, morphologic computed tomography/magnetic resonance imaging (MRI), or positron emission tomography–computed tomography have significant limitations because of technical, biological, or anatomical reasons. Therefore, there is a great clinical need for more precise, reliable, and noninvasive N-staging in patients with solid tumors. Using ultrasmall superparamagnetic particles of ironoxide (USPIO)-enhanced MRI offers noninvasive diagnostic possibilities for N-staging of different types of cancer, including the 4 examples given in this work (head and neck cancer, esophageal cancer, rectal cancer, and prostate cancer). The excellent soft tissue contrast of MRI and an USPIO-based differentiation of metastatic versus nonmetastatic lymph nodes can enable more precise therapy and, therefore, fewer side effects, essentially in cancer patients in oligometastatic disease stage. By discussing 3 important questions in this article, we explain why lymph node staging is so important, why the timing for more accurate N-staging is right, and how it can be done with MRI. We illustrate this with the newest developments in magnetic resonance methodology enabling the use of USPIO-enhanced MRI at ultrahigh magnetic field strength and in moving parts of the body like upper abdomen or mediastinum. For prostate cancer, a comparison with radionuclide tracers connected to prostate specific membrane antigen is made. Under consideration also is the use of MRI for improvement of ex vivo cancer diagnostics. Further scientific and clinical development is needed to assess the accuracy of USPIO-enhanced MRI of detecting small metastatic deposits for different cancer types in different anatomical locations and to broaden the indications for the use of (USPIO-enhanced) MRI in lymph node imaging in clinical practice.
Factors Influencing US Physician and Surgeon Suicide Rates 2003 to 2017
Authors: Elkbuli Adel , Sutherland Mason , Shepherd Aaron , Kinslow Kyle , Liu Huazhi , Ang Darwin , McKenney Mark
Published: November 2020

Background and Objectives:

With the rate of physician suicide increasing, more research is needed to implement adequate prevention interventions. This study aims to identify trends and patterns in physician/surgeon suicide and the key factors influencing physician suicide. We hope such information can highlight areas for targeted interventions to decrease physician suicide.

Methods:

Review of Centers for Disease Control and Preventions National Violent Death Reporting System (NVDRS) for 2003 to 2017 of physician and dentists dying by suicide. Twenty-eight medical, surgical, and dental specialties were included.

Results:

Nine hundred five reported suicides were reviewed. Physician suicides increased from 2003 to 2017. Majority surgeons’ suicides were middle-aged, White males. Orthopedic surgeons had the highest prevalence of suicide among surgical fields (28.2%). Black/African American surgeons were 56% less likely [odds ratio (OR) = 0.44, 95% confidence interval (CI): 0.06-3.16] and Asian/Pacific Islander were 438% more likely (OR = 5.38, 95% CI: 2.13–13.56) to die by suicide. Surgeons were 362% more likely to have a history of a mental disorder (OR = 4.62, 95% CI: 2.71–7.85), were 139% more likely to use alcohol (OR = 2.39, 95% CI: 1.36–4.21), and were 289% more likely to have experienced civil/legal issues (OR = 3.89, 95% CI: 1.36–11.11).

Conclusions:

The prevalence of physician suicide increased over the 2003 to 2017 time-frame with over a third of deaths occurring from 2015 to 2017. Among surgeons, orthopedics has the highest prevalence of reported suicide.

Risk factors for surgeon suicide include Asian/Pacific Islander race/ethnicity, older age, history of mental disorder, alcohol use, and civil/legal issues.
Time-varying Reproductive Rates for SARS-CoV-2 and its Implications as a Means of Disease Surveillance on Lockdown Restrictions
Authors: Toraih Eman A. , Hussein Mohammad H. , Elshazli Rami M. , Fawzy Manal S. , Houghton August , Tatum Danielle , Killackey Mary , Kandil Emad , Duchesne Juan
Published: November 2020

Objective:

To quantify the time-varying reproductive rates for SARS-CoV-2 and its implication in Louisiana.

Summary of Background Data:

Basic reproductive number (R

0
) and effective reproductive number (R

e
or R

t
) are 2 measures of the ability of an infectious agent to spread in the environment. They differ in that R

0
assumes zero immunity in the population, while R

e
or R

t
accounts for change over time. Reproductive number modeling is influenced by several factors, including serial interval, the time between the onset of symptoms in an infector, and a secondary case. Quantification of the ability of a pathogen to spread is essential in guiding policy.

Methods:

Here, we construct epidemic curves and calculate daily R

t
values for the state of Louisiana and each of its 9 regions.

Results:

Our results demonstrated variation over both time and geography in calculated R

0
and R

t
values. Generally, as time has progressed, predicted R

0
and R

t
values have decreased. In Louisiana, mean R

t
was calculated at 3.07 in March and 0.82 by May. A reproductive number less than one is important as it indicates infectious spread will decline with time. The most recent finding of mean R

t
= 0.82 is important. It stands in stark contrast to the situation in April when New Orleans, Louisiana, had the highest per capita coronavirus mortality rate in the United States – twice that of New York City and 4 times the rate in Seattle.

Conclusion:

As locations around the world begin to lift restrictions, monitoring of infectious spread will be essential.
Examining state-dependent effects of transcranial direct current stimulation on visual search and executive function tasks
Authors: Brunyé Tad T. , Elliott Grace , Loverro Kari
Published: November 2020

Objective

The aim of this study was to evaluate whether the effects of transcranial direct current stimulation (tDCS) on cognitive performance are influenced by the state-dependency of targeted cortical regions.

Methods

In a mixed within- and between-participants design, we targeted either the right parietal or left dorsolateral prefrontal cortex and measured effects on visual search versus inhibitory control (respectively). Critically, during active and sham stimulation, participants were exposed to an unrelated or task-congruent prime.

Results

Analyses examined whether priming induced state-dependent changes in behavior on a subsequent visual search or inhibitory control task. Results demonstrated consistent support for the null hypothesis, with neither tDCS nor priming influencing behavioral outcomes.

Conclusions

This outcome does not provide direct support for state-dependency or activity-selectivity models of tDCS effects on cognitive outcomes. We discuss the possibility that behavioral patterns supporting these mechanistic models may only be found when the priming and outcome tasks share critical neurocognitive features. Overall, we found no evidence that offline (pretask) tDCS targeting the right parietal or left dorsolateral prefrontal induces reliable changes in visual search or inhibitory control behavior, and this pattern is not modulated by state-dependency induced by priming task-related activity.
The upper atmospheres of Uranus and Neptune
Authors: Melin Henrik
Published: November 2020

We review the current understanding of the upper atmospheres of Uranus and Neptune, and explore the upcoming opportunities available to study these exciting planets. The ice giants are the least understood planets in the solar system, having been only visited by a single spacecraft, in 1986 and 1989, respectively. The upper atmosphere plays a critical role in connecting the atmosphere to the forces and processes contained within the magnetic field. For example, auroral current systems can drive charged particles into the atmosphere, heating it by way of Joule heating. Ground-based observations of H3+provides a powerful remote diagnostic of the physical properties and processes that occur within the upper atmosphere, and a rich dataset exists for Uranus. These observations span almost three decades and have revealed that the upper atmosphere has continuously cooled between 1992 and 2018 at about 8 K/year, from approximately 750 K to approximately 500 K. The reason for this trend remain unclear, but could be related to seasonally driven changes in the Joule heating rates due to the tilted and offset magnetic field, or could be related to changing vertical distributions of hydrocarbons. H3+has not yet been detected at Neptune, but this discovery provides low-hanging fruit for upcoming facilities such as the James Webb Space Telescope and the next generation of 30 m telescopes. Detecting H3+at Neptune would enable the characterization of its upper atmosphere for the first time since 1989. To fully understand the ice giants, we need dedicated orbital missions, in the same way the Cassini spacecraft explored Saturn. Only by combiningin situobservations of the magnetic field with in-orbit remote sensing can we get the complete picture of how energy moves between the atmosphere and the magnetic field.

This article is part of a discussion meeting issue ‘Future exploration of ice giant systems’.
Ice giant magnetospheres
Authors: Paty Carol , Arridge Chris S. , Cohen Ian J. , DiBraccio Gina A. , Ebert Robert W. , Rymer Abigail M.
Published: November 2020

The ice giant planets provide some of the most interesting natural laboratories for studying the influence of large obliquities, rapid rotation, highly asymmetric magnetic fields and wide-ranging Alfvénic and sonic Mach numbers on magnetospheric processes. The geometries of the solar wind–magnetosphere interaction at the ice giants vary dramatically on diurnal timescales due to the large tilt of the magnetic axis relative to each planet's rotational axis and the apparent off-centred nature of the magnetic field. There is also a seasonal effect on this interaction geometry due to the large obliquity of each planet (especially Uranus). Within situobservations at Uranus and Neptune limited to a single encounter by the Voyager 2 spacecraft, a growing number of analytical and numerical models have been put forward to characterize these unique magnetospheres and test hypotheses related to the magnetic structures and the distribution of plasma observed. Yet many questions regarding magnetospheric structure and dynamics, magnetospheric coupling to the ionosphere and atmosphere, and potential interactions with orbiting satellites remain unanswered. Continuing to study and explore ice giant magnetospheres is important for comparative planetology as they represent critical benchmarks on a broad spectrum of planetary magnetospheric interactions, and provide insight beyond the scope of our own Solar System with implications for exoplanet magnetospheres and magnetic reversals.

This article is part of a discussion meeting issue ‘Future exploration of ice giant systems'.
Enabling technologies for ice giant exploration
Authors: Spilker Thomas R.
Published: November 2020

Future missions to an ice giant planet, especially orbital missions, are technologically challenging. But with one exception, radioisotope power sources (RPSs), the technologies that would enable such missions are currently available. RPSs are not a new technology, but devices used in the past that are appropriate to an ice giant mission are no longer available without engineering development work (currently unfunded), and it is uncertain whether the new NASA unit under development will be available for flight in time to take advantage of the best transfer trajectories of the next 15 years. This paper describes technologies already in hand that enable an ice giant mission, but for them to be useful they must be maintained. If an enabling technology is lost a replacement must be developed, potentially impacting the cost and schedule of a mission. In addition to the enabling technologies, there are a number of technologies that, while not enabling, could greatly enhance the science return and science value of a mission, making the programmatic aspects of approval an easier task and the funding of those development tasks a high priority.

This article is part of a discussion meeting issue ‘Future exploration of ice giant systems'.
Genome-based classification of Calidifontibacillus erzurumensis gen. nov., sp. nov., isolated from a hot spring in Turkey, with reclassification of Bacillus azotoformans as Calidifontibacillus azotoformans comb. nov. and Bacillus oryziterrae as Calidifontibacillus oryziterrae comb. nov.
Authors: Adiguzel Ahmet , Ay Hilal , Baltaci Mustafa Ozkan , Akbulut Sumeyya , Albayrak Seyda , Omeroglu Mehmet Akif
Published: November 2020

A novel Gram-stain-positive, rod-shaped, endospore-forming, motile, aerobic bacterium, designated as P2T, was isolated from a hot spring water sample collected from Ilica-Erzurum, Turkey. Phylogenetic analyses based on 16S rRNA gene sequence comparisons affiliated strain P2T with the genus

Bacillus

, and the strain showed the highest sequence identity to

Bacillus azotoformans

NBRC 15712T (96.7 %). However, the pairwise sequence comparisons of the 16S rRNA genes revealed that strain P2T shared only 94.7 % sequence identity with

Bacillus subtilis

subsp.

subtilis

NCIB 3610T, indicating that strain P2T might not be a member of the genus

Bacillus

. The digital DNA–DNA hybridization and average nucleotide identity values between strain P2T and

B. azotoformans

NBRC 15712T were 19.8 and 74.2 %, respectively. The cell-wall peptidoglycan of strain P2T contained meso-diaminopimelic acid. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, an aminophospholipid, five unidentified phospholipids and two unidentified lipids while the predominant isoprenoid quinone was MK-7. The major fatty acids were iso-C15 : 0 and iso-C16 : 0. The draft genome of strain P2T was composed of 82 contigs and found to be 3.5 Mb with 36.1 mol% G+C content. The results of phylogenomic and phenotypic analyses revealed that strain P2T represents a novel genus in the family

Bacillaceae

, for which the name Calidifontibacillus erzurumensis gen. nov., sp. nov. is proposed. The type strain of Calidifontibacillus erzurumensis is P2T (=CECT 9886T=DSM 107530T=NCCB 100675T). Based on the results of the present study, it is also suggested that

Bacillus azotoformans

and

Bacillus oryziterrae

should be transferred to this novel genus as Calidifontibacillus azotoformans comb. nov. and Calidifontibacillus oryziterrae comb. nov., respectively.
Aquipluma nitroreducens gen. nov. sp. nov., a novel facultatively anaerobic bacterium isolated from a freshwater lake
Authors: Watanabe Miho , Kojima Hisaya , Fukui Manabu
Published: November 2020

A novel facultatively anaerobic, nitrate-reducing bacterium, designated MeG22T, was isolated from a freshwater lake in Japan. Cells of the strain were straight rods (0.8×2.5–10 µm), motile, and Gram-stain-negative. For growth, the optimum NaCl concentration was 0 % and the optimum temperature was 30 °C. Under anoxic conditions, strain MeG22T reduced nitrate to nitrite. Major cellular fatty acids were C15 : 1 ω6c (13.6 %), C17 : 0 (11.9 %), anteiso-C15 : 0 (10.6 %) and iso-C15 : 0 (10.6 %). The major respiratory quinone was menaquinone-7. The genome sequence of strain MeG22T consists of 5 712 279 bp with a G+C content of 40.3 mol%. Phylogenetic analysis based on the 16S rRNA gene revealed that the novel strain belonged to the family

Prolixibacteraceae

within the phylum

Bacteroidetes

. The closest relative of strain MeG22T was

Sunxiuqinia faeciviva

strain JAM-BA0302T with a 16S rRNA gene sequence similarity of 90.9 %. On the basis of phylogenetic and phenotypic characterization, Aquipluma nitroreducens, gen. nov., sp. nov., belonging to the family

Prolixibacteraceae

is proposed with the type strain MeG22T (=NBRC 112896T=DSM 106262T).
Effect of a Mobile-based Intervention on Mental Health in Frontline Healthcare Workers Against COVID-19: Protocol for a Randomized Controlled Trial
Authors: Serrano-Ripoll Maria J. , Ricci-Cabello Ignacio , Jiménez Rafael , Zamanillo-Campos Rocío , Yañez Juan Aina M. , Bennasar-Veny Miquel , Sitges Carolina , Gervilla Elena , Leiva Alfonso , García-Campayo Javier , García-Buades Maria Esther , García-Toro Mauro , Pastor Moreno Guadalupe , Ruiz-Perez Isabel , Alonso-Coello Pablo , Llobera Canaves Joan , Fiol-Deroque Maria A.
Published: November 2020

Aim

To evaluate the impact of a psychoeducational, mobile health intervention based on cognitive behavioural therapy and mindfulness-based approaches on the mental health of healthcare workers at the frontline against COVID-19 in Spain.

Design

We will carry out a two-week, individually randomised, parallel group, controlled trial. Participants will be individually randomised to receive the PsyCovidApp intervention or control App intervention.

Methods

The PsyCovidApp intervention will include five modules: emotional skills, lifestyle behaviour, work stress and burnout, social support, and practical tools. Healthcare workers having attended COVID-19 patients will be randomized to receive the PsyCovidApp intervention (intervention group) or a control App intervention (control group). A total of 440 healthcare workers will be necessary to assure statistical power. Measures will be collected telephonically by a team of psychologists at baseline and immediately after the two weeks intervention period. Measures will include stress, depression and anxiety (DASS-21 questionnaire – primary endpoint), insomnia (ISI), burnout (MBI-HSS), post-traumatic stress disorder (DTS), and self-efficacy (GSE). The study was funded in May 2020, and was ethically approved in June 2020. Trial participants, outcome assessors and data analysts will be blinded to group allocation.

Discussion

Despite the increasing use of mobile health interventions to deliver mental health care, this area of research is still on its infancy. This study will help increase the scientific evidence regarding the effectiveness of this type of intervention on this specific population and context.

Impact

Despite the lack of solid evidence about their effectiveness, mobile-based health interventions are already being widely implemented because of their low cost and high scalability. The findings from this study will help health services and organizations to make informed decisions in relation to the development and implementation of this type of interventions, allowing them pondering not only their attractive implementability features, but also empirical data about its benefits.

Clinical trial registration

NCT04393818 (ClinicalTrials.gov identifier)
Frequent testing and immunity-based staffing will help mitigate outbreaks in nursing home settings
Authors: Holmdahl Inga , Kahn Rebecca , Hay James , Buckee Caroline O. , Mina Michael
Published: November 2020

Background

Nursing homes and other long term care facilities have been disproportionately impacted by the COVID-19 pandemic. Strategies are urgently needed to reduce transmission in these vulnerable populations. We aim to evaluate the reduction in transmission in nursing homes achieved through contact-targeted interventions and testing.

Methods

We developed an agent-based Susceptible–Exposed– Infectious(Asymptomatic/Symptomatic)–Recovered (SEIR) model to examine SARS-CoV-2 transmission in nursing homes. Residents and staff are modelled individually; residents are split into two cohorts based on COVID-19 diagnosis. We evaluate the effectiveness of two contact-targeted interventions. In the resident cohorting intervention, recovered residents are moved back from the COVID (infected) cohort to the non-COVID (susceptible/uninfected) cohort. In the immunity-based staffing intervention, recovered staff, who we assume have protective immunity, are assigned to work in the non-COVID cohort, while susceptible staff work in the COVID cohort and are assumed to have high levels of protection from personal protective equipment. These interventions aim to reduce the fraction of people’s contacts that are presumed susceptible (and therefore potentially infected) and replace them with recovered (immune) contacts. We further evaluate two types of screening tests conducted with varying frequency: 1) rapid antigen testing and 2) PCR testing.

Results

The frequency and type of testing has a larger impact on the size of outbreaks than the cohorting and staffing interventions. The most effective testing strategy modeled is daily antigen testing. Under all screening testing strategies, the resident cohorting intervention and the immunity-based staffing intervention reduce the final size of the outbreak among residents, with the latter reducing it more. The efficacy of these interventions among staff varies by testing strategy and outbreak size.

Conclusions

Increasing the frequency of screening testing of all residents and staff, or even staff alone, in nursing homes has the potential to greatly reduce outbreaks in this vulnerable setting. Immunity-based staffing can further reduce spread at little or no additional cost and becomes particularly important when daily testing is not feasible.
COVID-19 Demographics, Acute Care Resource Use and Mortality by Age and Sex in Ontario, Canada: Population-based Retrospective Cohort Analysis
Authors: Mac Stephen , Barrett Kali , Khan Yasin A. , Naimark David MJ , Rosella Laura , Ximenes Raphael , Sander Beate
Published: November 2020

Background

Understanding resource use for COVID-19 is critical. We conducted a population-based cohort study using public health data to describe COVID-19 associated age- and sex-specific acute care use, length of stay (LOS), and mortality.

Methods

We used Ontario’s Case and Contact Management (CCM) Plus database of individuals who tested positive for COVID-19 in Ontario from March 1 to September 30, 2020 to determine age- and sex-specific hospitalizations, intensive care unit (ICU) admissions, invasive mechanical ventilation (IMV) use, LOS, and mortality. We stratified analyses by month of infection to study temporal trends and conducted subgroup analyses by long-term care residency.

Results

During the observation period, 56,476 COVID-19 cases were reported (72% < 60 years, 52% female). The proportion of cases shifted from older populations (> 60 years) to younger populations (10-39 years) over time. Overall, 10% of individuals were hospitalized, of those 22% were admitted to ICU, and 60% of those used IMV. Mean LOS for individuals in the ward, ICU without IMV, and ICU with IMV was 12.8, 8.5, 20.5 days, respectively. Mortality for individuals receiving care in the ward, ICU without IMV, and ICU with IMV was 24%, 30%, and 45%, respectively. All outcomes varied by age and decreased over time, overall and within age groups.

Interpretation

This descriptive study shows acute care use and mortality varying by age, and decreasing between March and September in Ontario. Improvements in clinical practice and changing risk distributions among those infected may contribute to fewer severe outcomes among those infected with COVID-19.
Elevated COVID-19 outcomes among persons living with diagnosed HIV infection in New York State: Results from a population-level match of HIV, COVID-19, and hospitalization databases
Authors: Tesoriero James M. , Swain Carol-Ann E. , Pierce Jennifer L. , Zamboni Lucila , Wu Meng , Holtgrave David R. , Gonzalez Charles J. , Udo Tomoko , Morne Johanne E. , Hart-Malloy Rachel , Rajulu Deepa T. , Leung Shu-Yin John , Rosenberg Eli S.
Published: November 2020

Background

New York State (NYS) has been an epicenter for both COVID-19 and HIV/AIDS epidemics. Persons Living with diagnosed HIV (PLWDH) may be more prone to COVID-19 infection and severe outcomes, yet few population-based studies have assessed the extent to which PLWDH are diagnosed, hospitalized, and have died with COVID-19, relative to non-PLWDH.

Methods

NYS HIV surveillance, COVID-19 laboratory confirmed diagnoses, and hospitalization databases were matched. COVID-19 diagnoses, hospitalization, and in-hospital death rates comparing PLWDH to non-PLWDH were computed, with unadjusted rate ratios (RR) and indirect standardized RR (sRR), adjusting for sex, age, and region. Adjusted RR (aRR) for outcomes among PLWDH were assessed by age/CD4-defined HIV disease stage, and viral load suppression, using Poisson regression models.

Results

From March 1-June 7, 2020, PLWDH were more frequently diagnosed with COVID-19 than non-PLWDH in unadjusted (RR [95% confidence interval (CI)]: 1.43[1.38-1.48), 2,988 PLWDH], but not in adjusted comparisons (sRR [95% CI]: 0.94[0.91-0.97]). Per-population COVID-19 hospitalization was higher among PLWDH (RR [95% CI]: 2.61[2.45-2.79], sRR [95% CI]: 1.38[1.29-1.47], 896 PLWDH), as was in-hospital death (RR [95% CI]: 2.55[2.22-2.93], sRR [95%CI]: 1.23 [1.07-1.40], 207 PLWDH), albeit not among those hospitalized (sRR [95% CI]: 0.96[0.83-1.09]). Among PLWDH, hospitalization risk increased with disease progression from HIV Stage 1 to Stage 2 (aRR [95% CI]:1.27[1.09-1.47]) and Stage 3 (aRR [95% CI]: 1.54[1.24-1.91]), and for those virally unsuppressed (aRR [95% CI]: 1.54[1.24-1.91]).

Conclusion

PLWDH experienced poorer COVID-related outcomes relative to non-PLWDH, with 1-in-522 PLWDH dying with COVID-19, seemingly driven by higher rates of severe disease requiring hospitalization.
Quality of life and patient-reported outcomes following proton therapy for oropharyngeal carcinoma: a systematic review
Authors: Yahya Noorazrul , Manan Hanani A.
Published: November 2020

Background

Complex anatomy surrounding the oropharynx makes proton therapy (PT) especially intensity-modulated PT (IMPT) a good option due to its ability to reduce the volume of irradiated healthy tissues. Dosimetric improvement may not translate to clinically relevant benefit. As outcome data are emerging, we aimed to systematically review current evidence of the quality of life (QOL) and patient-reported outcomes (PRO) following PT of oropharyngeal carcinoma (OC).

Materials and Methods

We searched PubMed and Scopus electronic databases to identify eligible reports on QOL and PRO following PT of OC according to PRISMA guidelines. Reports were extracted for information on demographics, main results and clinical and dose factors correlates.

Results

Six reports were selected from which four compared between PT and photon-based therapy. All endpoints where significant differences were found favour PT. The change following treatment improves but never to the baseline level.

Conclusion

Available evidence suggests that PT causes less QOL deterioration and PRO compared to photon therapy. Whether or not it is cost-effective should be a subject of further investigation.
Wastewater Analysis of SARS-CoV-2 as a Predictive Metric of Positivity Rate for a Major Metropolis
Authors: Stadler L.B. , Ensor K.B. , Clark J.R. , Kalvapalle P. , LaTurner Z. W. , Mojica L. , Terwilliger A. , Zhuo Y. , Ali P. , Avadhanula V. , Bertolusso R. , Crosby T. , Hernandez H. , Hollstein M. , Weesner K. , Zong D.M. , Persse D. , Piedra P.A. , Maresso A.W. , Hopkins L.
Published: November 2020

Wastewater monitoring for SARS-CoV-2 has been suggested as an epidemiological indicator of community infection dynamics and disease prevalence. We report wastewater viral RNA levels of SARS-CoV-2 in a major metropolis serving over 3.6 million people geographically spread over 39 distinct sampling sites. Viral RNA levels were followed weekly for 22 weeks, both before, during, and after a major surge in cases, and simultaneously by two independent laboratories. We found SARS-CoV-2 RNA wastewater levels were a strong predictive indicator of trends in the nasal positivity rate two-weeks in advance. Furthermore, wastewater viral RNA loads demonstrated robust tracking of positivity rate for populations served by individual treatment plants, findings which were used in real-time to make public health interventions, including deployment of testing and education strike teams.
Regulation of touch dependantde novoroot regeneration in Arabidopsis
Authors: Shanmukhan Anju Pallipurath , Mathew Mabel Maria , Aiyaz Mohammed , Kareem Abdul , Radhakrishnan Dhanya , Prasad Kalika
Published: November 2020

The versatile regeneration capability of leaves enable even a detached Arabidopsis leaf to yield two kinds of regenerative responses namely, wound healing at the cut end in form of callus formation or de novo root regeneration (DNRR). Using various experimental approaches, we show that the factor favouring DNRR over callus formation seems to be a mechanical cue, possibly touch, at the cut end of the detached leaf. Here, we show that the forced expression of a PLETHORA transcription factor can bypass the need for touch to initiate DNRR. Our findings provide a genetic frame-work for touch dependant DNRR and suggest that a core PLT transcription regulatory module acts in response to mechano-sensing stimuli.
A new duck genome reveals conserved and convergently evolved chromosome architectures of birds and mammals
Authors: Li Jing , Zhang Jilin , Liu Jing , Zhou Yang , Cai Cheng , Xu Luohao , Dai Xuelei , Feng Shaohong , Guo Chunxue , Rao Jinpeng , Wei Kai , Jarvis Erich D. , Jiang Yu , Zhou Zhengkui , Zhang Guojie , Zhou Qi
Published: November 2020

Background

Ducks have a typical avian karyotype that consists of macro- and microchromosomes, but a pair of much less differentiated ZW sex chromosomes compared to chicken. To elucidate the evolution of chromosome architectures between duck and chicken, and between birds and mammals, we produced a nearly complete chromosomal assembly of a female Pekin duck by combining long-read sequencing and multiplatform scaffolding techniques.

Results

The major improvement of genome assembly and annotation quality resulted from successful resolution of lineage-specific propagated repeats that fragmented the previous Illumina-based assembly. We found that the duck topologically associated domains (TAD) are demarcated by putative binding sites of the insulator protein CTCF, housekeeping genes, or transitions of active/inactive chromatin compartments, indicating the conserved mechanisms of spatial chromosome folding with mammals. There are extensive overlaps of TAD boundaries between duck and chicken, and also between the TAD boundaries and chromosome inversion breakpoints. This suggests strong natural selection on maintaining regulatory domain integrity, or vulnerability of TAD boundaries to DNA double-strand breaks. The duck W chromosome retains 2.5-fold more genes relative to chicken. Similar to the independently evolved human Y chromosome, the duck W evolved massive dispersed palindromic structures, and a pattern of sequence divergence with the Z chromosome that reflects stepwise suppression of homologous recombination.

Conclusions

Our results provide novel insights into the conserved and convergently evolved chromosome features of birds and mammals, and also importantly add to the genomic resources for poultry studies.
An Abundant New Saponin-Polybromophenol Antibiotic (CU1) fromCassia fistulaBark Against Multi-Drug Resistant Bacteria Targeting RNA Polymerase
Authors: Chakraborty Asit Kumar , Saha Sourajit , Poria Kousik , Samanta Tanmoy , Gautam Sudhanshu , Mukhopadhyay Jayanta
Published: November 2020

Spread of multidrug-resistant infections is a threat to human race and need for new drug development is great. Bark ethanol extract ofCassia fistulainhibited MDR bacteria isolated from Ganga River water, human and animal. On TLC, a gray colour major band ran fast (CU1; 6.6% of bark and ~30% of crude extract) which quickly purified on HPLC C18column at 3 min. Chemical assays suggested a triterpene linked to polyphenol known as saponin. CHN Elements analysis (35.9% C; 5.5% H) did not identified nitrogen suggesting a polyphenol or glycoside. VU-Vis spectra gave high peak at below 200nm with a secondary peak at 275nm with minor hinge at 578nm indicating a fused ring with bromo-polyphenol. CU1 Mass (897 Daltons) with fragments of 515, 325, 269, 180 daltons and six halogen substitutions reflected by 82 molecular mass of DBr deviate six larger fragments. FT-IR suggested broad band at 3500-3000 cm−1for −OH where as two strong peaks at 1552cm−1for aromatic C=C and 1408cm−1for phenol. Proton-NMR confirmed polymeric phenol at δ 4.86-4.91 ppm and tetratet at δ3.57-3.618 ppm with phenolic bromo-substituents. Carbon-NMR identified a strong peak at δ=23.7ppm for many C-Br and at 165ppm for a polybenzoid compound. CU1 inhibited the RNA Polymerase ofE. coli(IC50=23μg/ml) andM. tuberculosis(IC50=34μg/ml) but not DNA polymerase. Gel shift assays demonstrated that CU1 drug interacted with enzyme and inhibited its binding to open promoter complex. Thus, CU1 phyto-chemical is an alternative safer and low cost drug against MDR-TB as well as other MDR pathogens.
IRIS-FGM: an integrative single-cell RNA-Seq interpretation system for functional gene module analysis
Authors: Chang Yuzhou , Allen Carter , Wan Changlin , Chung Dongjun , Zhang Chi , Li Zihai , Ma Qin
Published: November 2020

Single-cell RNA-Seq (scRNA-Seq) data is useful in discovering cell heterogeneity and signature genes in specific cell populations in cancer and other complex diseases. Specifically, the investigation of functional gene modules (FGM) can help to understand gene interactive networks and complex biological processes. QUBIC2 is recognized as one of the most efficient and effective tools for FGM identification from scRNA-Seq data. However, its limited availability to a C implementation restricted its application to only a few downstream analyses functionalities. We developed an R package named IRIS-FGM (Integrative scRNA-Seq Interpretation System for Functional Gene Module analysis) to support the investigation of FGMs and cell clustering using scRNA-Seq data. Empowered by QUBIC2, IRIS-FGM can effectively identify co-expressed and co-regulated FGMs, predict cell types/clusters, uncover differentially expressed genes, and perform functional enrichment analysis. It is noteworthy that IRIS-FGM can also takes Seurat objects as input, which facilitate easy integration with existing analysis pipeline.

Availability and Implementation

IRIS-FGM is implemented in R environment (as of version 3.6) with the source code freely available athttps://github.com/OSU-BMBL/IRIS-FGM

Contact

qin.ma@osumc.edu

Supplementary information

Supplementary data are available atBioinformaticsonline.
Spatiotemporal Variations in Growth Rate and Virulence Plasmid Copy Number duringYersinia pseudotuberculosisInfection
Authors: Schneiders Stephan , Hechard Tifaine , Edgren Tomas , Avican Kemal , Fällman Maria , Fahlgren Anna , Wang Helen
Published: November 2020

PathogenicYersinia spp.depend on the activity of a potent virulence plasmid-encodedysc/yoptype 3 secretion system (T3SS) to colonize hosts and cause disease. It was recently shown thatY. pseudotuberculosisup-regulates the virulence plasmid copy number (PCN) during infection and the resulting elevated gene dose of plasmid-encoded T3SS genes is essential for virulence. When and how this novel regulatory mechanism is deployed and regulates the replication of the virulence plasmid during infection is unknown. In the current study, we applied droplet digital PCR (ddPCR) to investigate the dynamics ofY. pseudotuberculosisvirulence PCN variations and growth rates in infected mouse organs. We demonstrated that both PCN and growth varied in different tissues and over time throughout the course of infection, indicating that the bacteria adapted to discrete microenvironments during infection. The PCN was highest in Peyer’s Patches and caecum during the clonal invasive phase of the infection, while the fastest growth rates were found in the draining mesenteric lymph nodes. In deeper, systemic organs, the PCN was lower and more modest growth rates were recorded. Our study indicates that increased gene dosage of the plasmid-encoded T3SS genes is most important early in the infection during invasion of the host. The described ddPCR approach will greatly simplify analyses of PCN, growth dynamics, and bacterial loads in infected tissues, and will be readily applicable to other infection models.

Importance

Studying pathogenic bacteria proliferating inside infected hosts is challenging using traditional methods, especially the transit and reversible genetic events. The bacteria are effectively diluted by the overwhelming number of host cells present in infected tissues. Using an innovative droplet digital PCR (ddPCR) approach, we have determined the virulence plasmid copy number (PCN) variations and growth rates ofYersiniaduring the course of infection in a mouse model. Here, we show that both the virulence plasmid copy number and bacterial growth rates display spatiotemporal variations in mice during infection. We demonstrate that the peak-to-trough ratio can be used as a proxy for determining the growth rate of invasive bacterial pathogen during infection, and ddPCR as the method of choice for quantifying DNA in host-pathogen interaction context. This proof-of-concept ddPCR approach can be easily applied for any bacterial pathogens and any infection models, for analysis of PCN, growth dynamics and bacterial loads.
In situ3D comparison ofChlorella pyrenoidosawith nuclear-irradiated mutagenic strains by using focused ion beam milling and cryo-electron tomography
Authors: Guo Wangbiao , Feng Lingchong , Wang Zhenyi , Guo Jiansheng , Park Donghyun , Carroll Brittany L. , Zhang Xing , Liu Jun , Cheng Jun
Published: November 2020

Microalgae are highly efficient photosynthetic organisms that hold enormous potential as sources of renewable energy. In particular,Chlorella pyrenoidosadisplays a rapid growth rate, high tolerance to light, and high lipid content, making it especially valuable for applications such as flue gas CO2fixation, biofuel production, and nutritional extracts. In order to unveil its full potential, it is necessary to characterize its subcellular architecture. Here, we achieved three-dimensional (3D) visualization of the architectures ofC. pyrenoidosacells, by combining focused ion beam scanning electron microscopy (FIB/SEM), cryo-FIB milling, and cryo-electron tomography (cryo-ET). These high-resolution images bring to light intricate features of intact organelles, including thylakoid membranes, pyrenoid, starch granules, mitochondria, nucleus, lipid droplets and vacuoles, as well as the fine architectures within the chloroplast, including the concave-convex pyrenoid, plastoglobules, thylakoid tips, and convergence zones. Significantly, comparative analysis of wild-type and nuclear-irradiated mutagenic strains determined that cell volume and surface area of mutant cells have increased substantially to 2.2-fold and 1.7-fold, respectively, consistent with up-regulation of the enzyme Rubisco and enhanced photosynthetic metabolic processes. Moreover, quantitative analysis established that the thylakoid membrane width in mutant cells increased to 1.3-fold, while the membrane gap decreased to 0.8-fold, possibly contributing to the higher biomass growth rate of mutant cells. Our work reveals the first 3D subcellular architectures ofC. pyrenoidosacell and provides a structural framework for unlocking the higher growth rate in microalgae relevant to a wide range of industrial applications.
“Dimerization of the Mineralocorticoid Receptor Ligand Binding Domain by helix 9, 10 and the F-domain”
Authors: Bianchetti Laurent , Sinar Deniz , Depenveiller Camille , Dejaegere Annick
Published: November 2020

In vertebrates, the mineralocorticoid receptor (MR) is a steroid-activated nuclear receptor (NR) that plays essential roles in water-electrolyte balance and blood pressure homeostasis. It belongs to the group of oxo-steroidian NRs, together with the glucocorticoid (GR), progesterone (PR), and androgen (AR) receptors. Classically, these oxo-steroidian NRs homodimerize and bind to specific genomic sequences to activate gene expression. NRs are multi-domain proteins, and dimerization is mediated by both the DNA (DBD) and ligand binding (LBD) domains, with the latter thought to provide the largest dimerization interface. However, at the structural level, the LBD dimerization of oxo-steroidian receptors has remained largely a matter of debate. This is linked to the receptor refractory expression, purification and crystallization. As a result, there is currently no consensus on a common homodimer assembly across the 4 receptors,i.e. GR, PR, AR and MR, despite their sequence homology. Examining the available MR LBD crystals and using widely plebiscited tools such as PISA, PRISM and EPPIC, and the MM/PBSA method, we have determined that an interface mediated by the helices H9 and H10 of the LBD as well as by the F domain presents the features of a biological protein-protein interaction surface. This interface which has been observed in both GRα and MR crystals, distinguished itself among other contacts and provided for the first time a homodimer architecture that is common to both oxo-steroidian receptors.