bluuebunny/crossref_metadata_2025 huggingface dataset:
Presurgical Short-Term Halo-Pelvic Traction for Severe Rigid Scoliosis (Cobb Angle >120°)
Authors: Wang Yu , Li Chunde , Liu Long , Li Hong , Yi Xiaodong
Published: October 2020

Study Design.

A 2-year follow-up review of 62 patients with severe rigid scoliosis (>120°).

Objective.

To evaluate the effectiveness and safety of halo-pelvic traction (HPT) for treating severe rigid scoliosis (>120°).

Summary of Background Data.

Severe rigid scoliosis (>120°) is still a challenge for spine surgeons. A combination of presurgical HPT traction, osteotomy, and internal fixation could be a safe and effective solution for these cases.

Methods.

We reviewed the records of all the patients with severe rigid scoliosis (>120°) treated with presurgical HPT from 2013 through 2017. Radiographic measurements were performed. The period of traction, estimated blood loss, operation time, complications, and bed rest period were recorded.

Results.

A total of 62 patients who had 2-year radiological follow-up were included in the study. In 30 patients, vertebral column resection (VCR) was performed aiming to achieve a better correction rate. In patients who received a VCR, the average preoperative Cobb angle was 133.6°, and the average correction rate at 2 years after surgery was 65.4%. Compared with the average height before treatment, at 2 years after surgery the average height was 12.5 cm greater. In patients who did NOT received VCR, the average preoperative Cobb angle was 131.5°, and the average correction rate at 2 years after surgery was 64.1%. Compared with the average height before treatment, at 2 years after surgery the average height was 14.0 cm greater. Common complications during HPT included infected pelvic pins, brachial plexus palsy, and weakness of the lower extremities. No patients experienced permanent neurological deficits or death.

Conclusion.

For severe rigid scoliosis with a Cobb angle greater than 120°, a combination of short-term presurgical HPT and posterior surgery is an effective and safe solution. After 4 to 6 weeks of presurgical HPT the Cobb angle can be decreased by approximately 50%, providing a favorable condition for spine corrective surgery.

Level of Evidence: 3
Dabrafenib and trametinib induced pancreatitis: a case report and review of the literature
Authors: Ogliari Francesca R. , Rodolfo Masera Giovanni L. , Gueli Rossana , Chini Claudio
Published: October 2020

Approximately 50% of melanomas are characterized by BRAF mutation (V600E in 90% of cases), that predicts more aggressive behaviour. This mutation is the target of dabrafenib, an anti-BRAF tyrosine-kinase inhibitor (TKI), that together with trametinib, anti-MEK TKI, is approved for first-line treatment of metastatic melanoma due to significant benefit in overall and progression-free survival. Most common treatment-related adverse events are pyrexia, chills, fatigue, rash, nausea, vomiting, and diarrhoea. This case report aims to present another less common adverse event of combined anti-BRAF and anti-MEK treatment. Our patient, after 4 months on target-therapy, experienced sudden deep abdominal pain. At the initial work-out at the emergency department, increase in serum lipase was detected and radiological findings were consistent with acute pancreatitis. Admitted to the hospital, other causes were ruled out and target-therapy was discontinued with symptoms improvement. Radiological and clinical follow-up was performed and a diagnosis of drug-induced pancreatitis was made. After few days of medical support with analgesia and antibiotic, the patient felt better and was discharged; target-therapy was permanently interrupted. Searching the literature, not so many cases of iatrogenic pancreatitis are described with this TKI combination, therefore, we have reported it as a rare but life-threatening adverse event that should be investigated whenever conceivable.
Online educational curriculum in pediatric epilepsy: A pilot study
Authors: Winesett Steven. Parrish , Amankwah Ernest K. , Nguyen Anh Thy H. , Sibinga Erica
Published: October 2020

Recent projections suggest that increasing numbers of nurse practitioners (NPs) and physician assistants (PAs) will be needed to meet the increasing need for pediatric neurology expertise. This pilot study assessed feasibility and preliminary effectiveness of an online curriculum designed to impact knowledge, skills, attitudes, and behaviors of NPs/PAs treating patients with pediatric epilepsy. Ten-session online curriculum was developed using previous experience and published recommendations to improve knowledge, electroencephalogram (EEG) skills, attitudes, and behaviors related to treating patients with pediatric epilepsy. Participants were NPs and PAs recruited from regional pediatric neurology practices. Three successive 10-week courses were provided. Attendance and completion were used to assess feasibility. Knowledge, EEG skills, attitudes, and behaviors were evaluated using pretest versus posttest questionnaires and compared analytically using a paired t-test and McNemar test. Twenty-nine NPs/PAs started the course, with typical attendance ∼85%. Twenty-two participants (76%) completed the course. Completers showed significant improvements in medication knowledge (premedication: mean = 74.6, SD = 16.4; postmedication: mean: 88.3, SD = 14.0; p = .001), EEG skills (premedication: mean = 44.8, SD = 24.4; postmedication: mean: 77.3, SD = 19.8; p < .001), and several measures of attitude and behavior. This pilot study shows feasibility and potential educational benefit of a 10-hour online course on pediatric epilepsy and may provide a convenient and effective option for continuing education for hard-to-reach students.
Introducing telehealth skills into the Doctor of Nursing Practice curriculum
Authors: Love Rene , Carrington Jane M.
Published: October 2020

Telehealth training was important for nurse practitioner (NP) students prior to the COVID-19 pandemic, but now it is essential. Training in telehealth allows access to health care for vulnerable populations in rural health areas and beyond. As the future of health care delivery changes, providers will be required to use this technology. Therefore, it is imperative that such training become part of NP education to prepare students to be technologically competent providers in the 21st century. The objective of this educational pilot project was to educate Doctor of Nursing Practice nurse practitioner students to conduct patient interviews and provide interprofessional collaboration using telehealth. The project addressed a gap in the literature on planning for simulations from varying NP specialties and provided feedback from standardized patients on their experiences. A total of 83 students from four specialty tracks received telehealth education. Students then interviewed simulated patients and provided a collaborating report. The students and patients were asked to complete questionnaires to assess the modules and the experience itself. Quantitative descriptive data were gathered, and qualitative themes were obtained from open-ended questions. Both the students and simulated patients indicated that they appreciated the ease and convenience of interviewing patients through technology. Both struggled with issues related to the technology and the need to have backup systems available. The students demonstrated that they were very capable of using telehealth and were generally very positive about the experience.
Advancing the health of homeless populations through vaccinations
Authors: Washington-Brown Linda , Cirilo Rose Wimbish
Published: October 2020

Background:

Homeless individuals and families are at an increased risk for contracting and transmitting communicable infections and diseases. Due to poor living conditions and limited access to health care resources, homeless people of all ages are vulnerable to acquiring communicable infections, such as pneumococcal pneumonia.

Local problem:

Less than 40% of sheltered and unsheltered homeless people in South Florida, who were interviewed for this project, knew their immunization status and/or were up-to-date with their recommended vaccine histories.

Methods:

The immunization project implemented a five-step process to provide pneumococcus (pneumococcal polysaccharide vaccine 23) and Prevnar 13 vaccinations to a convenience sample of adult homeless men and women (N = 209) participants, who completed the financial eligibility form (J11) during their intake process to admission, for sheltered services from two local clinics.

Interventions:

To promote herd immunity, the five-step process was followed. As per the Centers for Disease Control and Prevention guidelines, initial training was provided to homeless shelter health care providers on vaccine storage, handling, and vaccination. A subsequent 1-week follow-up was completed with participants to determine if any delayed vaccination adverse reactions occurred.

Results:

Descriptive statistics was used to examine data from the initial project implementation. Findings indicated that more African Americans (n = 117) participated in the project than Whites (n = 50), Hispanics (n = 35), or Haitians (n = 7).

Conclusions:

Homeless individuals experience illnesses that are preventable through involvement with a structured immunization program. Collectively, nurse practitioners can reduce barriers to immunization by increasing vaccine coverage and introducing incremental policy changes that enhance the health status among homeless populations.
Heterozygous intragenic deletions of FREM1 are not associated with trigonocephaly
Authors: Dawson Angelika J. , Hovanes Karine , Liu Jing , Marles Sandra , Greenberg Cheryl , Mhanni Aziz , Chudley Albert , Frosk Patrick , Sahoo Trilochan , Schanze Denny , Zenker Martin
Published: October 2020

Recessive mutations in FRAS1-related extracellular matrix 1 (FREM1) are associated with two rare genetic disorders, Manitoba-oculo-tricho-anal (MOTA) and bifid nose with or without anorectal and renal anomalies (BNAR). Fraser syndrome is a more severe disorder that shows phenotypic overlap with both MOTA and anorectal and renal anomalies and results from mutations in FRAS1, FREM2 and GRIP1. Heterozygous missense mutations in FREM1 were reported in association with isolated trigonocephaly with dominant inheritance and incomplete penetrance. Moreover, large deletions encompassing FREM1 have been reported in association with a syndromic form of trigonocephaly and were designated as trigonocephaly type 2. Trigonocephaly results from premature closure of the metopic suture and typically manifests as a form of nonsyndromic craniosynostosis. We report on 20 patients evaluated for developmental delay and without abnormal metopic suture. Chromosomal microarray analysis revealed heterozygous FREM1 deletions in 18 patients and in 4 phenotypically normal parents. Two patients were diagnosed with MOTA and had homozygous FREM1 deletions. Therefore, although our results are consistent with the previous reports of homozygous deletions causing MOTA, we report no association between heterozygous FREM1 deletions and trigonocephaly in this cohort.
Bone Marrow Reconversion With Reambulation
Authors: Liu Tammy , Melkus Gerd , Ramsay Tim , Sheikh Adnan , Laneuville Odette , Trudel Guy
Published: October 2020

Objectives

Marrow adipose tissue may be modulated by physical activity and reambulation after inactivity. The aim of this study was to measure the effect of reambulation for up to 2 years after 60 days of bed rest on the lumbar bone marrow composition.

Methods

In a prospective clinical trial, 20 healthy men participated in a 60-day, 6-degree head-down tilt bed rest study. Serial 3-T magnetic resonance (MR) imaging measures of the lumbar spine were performed at baseline, after 57 days of bed rest, and at 30, 360, and 720 days of reambulation (100 MR imaging scans). Proton density with and without fat saturation, 2-point Dixon, and single-voxel MR spectroscopy techniques were used to assess bone marrow composition (300 measures). Erythropoiesis was measured using hematocrit, reticulocyte, and ferritin. Also, participants randomly received either a nutritional intervention composed of polyphenols, omega-3, vitamin E, and selenium or a normal diet.

Results

Thirty days of reambulation after 60 days of bed rest caused a marked decrease of the mean lumbar vertebral fat fraction (VFF) (−9.2 ± 1.6 percentage points, −8.0 ± 1.3 percentage points, and −12.7 ± 1.2 percentage points compared with baseline using proton density, Dixon, MR spectroscopy, respectively; all 3, P < 0.05). Reambulation also decreased the fat saturation index (−5.3 ± 1.1 percentage points compared with baseline; P < 0.05). These coincided with lower hematocrit and ferritin and with increased reticulocytes at reambulation day 13 compared with baseline (all 3, P < 0.05). After 57 days of bed rest, the VFF was unchanged from baseline (all 3 MR techniques, P > 0.05); reambulation for 2 years returned the lumbar VFF to baseline values.

Interpretation

This longitudinal trial established that 30 days of reambulation after 60 days of bed rest constituted a powerful stimulus for bone marrow reconversion. In this model, the enhanced erythropoiesis coupled with preferential consumption of fatty acids from regulated marrow adipose tissue to supply energy for erythropoiesis and bone anabolism may explain the lumbar vertebrae reconversion. These results will help interpreting bone marrow signal in ambulatory patients after long periods of bed rest.
Deformation Assessment of the Manually Pre-Bent Titanium Miniplates in Orthognathic Surgery With Finite Element Analysis
Authors: Liu Li-Nan , Li Jia-Yang , Li Ke-Han , Wu Qiong-Hui , Liu Yao , Luo En
Published: October 2020

This study summarized the literature regarding the application of pre-bent titanium miniplates in orthognathic surgery and evaluated the extra deformation of the manually pre-bent titanium miniplates via finite element analysis for acquiring higher surgical accuracy. The literature was reviewed with a chart. Three models of titanium miniplates with different thicknesses (1.0 mm, 0.8 mm, 0.6 mm) were created using COMSOL Multiphysics software for biomechanical behavior analysis. The 3 models were virtually bent into 5 angles (15 degree, 30 degree, 45 degree, 60 degree, 80 degree). respectively to simulate the preoperative virtual bending, then to simulate the practical manual bending via finite element analysis. The stresses and displacements of these models were recorded. The models from virtual bending simulation and manual bending simulation were registered to analyze the deviations. The results showed that the maximum stress and the displacement deviations between the virtual bending models and the manual bending models increased with the thickness and bending angle of the pre-bent miniplate models. To improve the surgical accuracy, measures should be applied to the manually pre-bent titanium miniplates to reduce the extra deformation when the plate being thicker and the bending angle being larger.
Carotid Sacrifice via Endonasal Clipping to Treat Carotid Injury in Extended Endoscopic Endonasal Surgery
Authors: Liu Bin , Tian Hailong , Wang Zhigang
Published: October 2020

Internal carotid artery (ICA) injury is a rare but disastrous complication during extended endoscopic endonasal surgery. The method of ICA sacrifice via endonasal clipping has only been reported in a few cases to treat ICA injury. To provide some technical experience of this method, here the authors present 2 cases of ICA injury during extended endoscopic endonasal surgery with 2-year follow-up. The 2-nostrils/4-hands technique was used to control the active bleeding. Based on the good collateral circulation status and the normal results of intraoperative electrophysiological monitoring, we sacrificed the injured ICAs via endonasal clipping. Both cases had a satisfying tumor resection rate and a good clinical outcome.
Evaluation of diastolic function in newly diagnosed hyperthyroid patients with preserved left ventricular systolic function
Authors: Shojaeifard Maryam , Davoudi Zahra , Erfanifar Azam , Fattahi Neisiani Hamed , Erami Sajad , Bakhshandeh Hooman , Mohammadi Khadije
Published: October 2020

Background

Diastolic dysfunction has been reported as a cardiovascular effect of hyperthyroidism, and is also supposed to be a cause of heart failure manifestations in the patients with preserved ejection fraction (EF).

Methods

For evaluation of diastolic function in hyperthyroid patients and also diastolic function during performing exercise stress echocardiography, we conducted this study on 25 newly diagnosed hyperthyroid patients compared to 26 healthy subjects as control group. Diastolic function of the patients at rest was assessed using these parameters as follows: left atrium volume index, tricuspid regurgitation (TR) velocity, mitral inflow early diastolic flow (E wave), tissue Doppler of mitral annular velocity (e′), E/e′ ratio, and isovolumic relaxation time (IVRT); and during exercise stress echocardiography, we judged diastolic response by measuring E/e′ ratio and TR velocity at the peak of stress.

Results

The mean age of the patients was 39.64 ± 12.23 years old and 52% of them were female. History of exertional dyspnea was found in 64% of patients. All the patients had normal diastolic function at the time of resting and there was no significant difference in diastolic parameters between the two groups except for IVRT, which was lower in hyperthyroid patients. Interestingly, no patients developed diastolic dysfunction during exercise stress echocardiography.

Conclusion

Our finding did not show diastolic dysfunction in hyperthyroid patients neither at rest nor during exercise echocardiography and did not support the hypothesis that diastolic dysfunction can be a cause of exertional intolerance and dyspnea in the patients with preserved EF.
Salifodinibacter halophilus gen. nov., sp. nov., a halophilic gammaproteobacterium in the family Salinisphaeraceae isolated from a salt mine in the Colombian Andes
Authors: Parada-Pinilla María Paula , Díaz-Cárdenas Carolina , López Gina , Díaz-Riaño Jorge Iván , Gonzalez Laura N. , Restrepo Silvia , Trujillo Martha E. , Baena Sandra
Published: October 2020

Two morphologically similar halophilic strains, named USBA 874 and USBA 960T, were isolated from water and sediment samples collected from the Zipaquirá salt mine in the Colombian Andes. Both isolates had non-spore-forming, Gram-stain-negative and motile cells that grew aerobically. The strains grew optimally at 30 °C, pH 7.0 and with 25 % NaCl (w/v). The isolates showed almost identical 16S rRNA gene sequences (99.0 % similarity). The predominant quinones of USBA-960T were Q-8, Q-7 and Q-9. The major cellular fatty acids were C19 : 0 cyclo ω8c, C18 : 0 and C16 : 0. According to 16S rRNA gene sequencing, the closest phylogenetic relatives are

Salinisphaera

species (similarity between 93.6 and 92.3 %),

Abyssibacter profundi

OUC007T (88.6 %) and

Oceanococcus atlanticus

22II-S10r2T (88.7 %). In addition, the result of genome blast distance phylogeny analysis between strains USBA 874 and USBA 960T,

Salinisphaera halophila

(YIM 95161T),

Salinisphaera shabanensis

(E1L3AT),

Salinisphaera orenii

(MK-B5T) and

Salinisphaera japonica

(YTM-1T) was 18.5 %. Other in silico species delineation analyses also showed low identity such as ANIb and ANIm values (<69.0 and <84.0 % respectively), TETRA (<0.81) and AAI values (<0.67). Genome sequencing of USBA 960T revealed a genome size of 2.47 Mbp and a G+C content of 59.71 mol%. Phylogenetic analysis of strains USBA 874 and USBA 960T indicated that they formed a different lineage within the family

Salinisphaeraceae

. Based on phenotypic and chemotaxonomic characteristics, phylogenetic analysis and DNA–DNA relatedness values, along with identity at whole genome level, it can be concluded that strains USBA 960T and USBA 874 represent a novel genus of the family

Salinisphaeraceae

and the name Salifodinibacter halophilus gen. nov., sp. nov. is proposed. The type strain is USBA 960T (CMPUJ U095T=CECT 30006T).
Transcriptome-wide expression profiling of Sporothrix schenckii yeast and mycelial forms and the establishment of the Sporothrix Genome DataBase
Authors: Giosa Domenico , Felice Maria Rosa , Giuffrè Letterio , Aiese Cigliano Riccardo , Paytuví-Gallart Andreu , Lo Passo Carla , Barresi Cinzia , D'Alessandro Enrico , Huang Huaiqiu , Criseo Giuseppe , Mora-Montes Héctor M. , de Hoog Sybren , Romeo Orazio
Published: October 2020

Sporothrix schenckii is a dimorphic fungus existing as mould in the environment and as yeast in the host. The morphological shift between mycelial/yeast phases is crucial for its virulence, but the transcriptional networks implicated in dimorphic transition are still not fully understood. Here, we report the global transcriptomic differences occurring between mould and yeast phases of S. schenckii, including changes in gene expression profiles associated with these distinct cellular phenotypes. Moreover, we also propose a new genome annotation, which reveals a more complex transcriptional architecture than previously assumed. Using RNA-seq, we identified a total of 17 307 genes, of which 11 217 were classified as protein-encoding genes, whereas 6090 were designated as non-coding RNAs (ncRNAs). Approximately ~71 % of all annotated genes were found to overlap and the different-strand overlapping type was the most common. Gene expression analysis revealed that 8795 genes were differentially regulated among yeast and mould forms. Differential gene expression was also observed for antisense ncRNAs overlapping neighbouring protein-encoding genes. The release of transcriptome-wide data and the establishment of the Sporothrix Genome DataBase (http://sporothrixgenomedatabase.unime.it) represent an important milestone for Sporothrix research, because they provide a strong basis for future studies on the molecular pathways involved in numerous biological processes.
Predictors of Death in Severe COVID-19 Patients at Millennium COVID-19 Care Center in Ethiopia: A Case-Control Study
Authors: Maru Endalkachew H. , Leulseged Tigist W. , Hassen Ishmael S. , Zewde Wuletaw C. , Chamesew Nigat W. , Abebe Daniel S. , Jagema Tariku B. , Bayisa Abdi B. , Gezahegn Mesfin A. , Tefera Oli S. , Shiferaw Wondmagegn G. , Admasu Teketel T.
Published: October 2020

Background

As the number of new cases and death due to COVID-19 is increasing, understanding the characteristics of severe COVID-19 patients and identifying characteristics that lead to death is a key to make an informed decision. In Ethiopia, as of September 27, 2020, a total of 72,700 cases and 1165 deaths were reported.

Objective

The study aimed to assess the determinants of death in Severe COVID-19 patients admitted to Millennium COVID-19 Care Center in Ethiopia.

Methods

A case-control study of 147 Severe COVID-19 patients (49 deaths and 98 discharged alive cases) was conducted from August to September 2020. A comparison of underlying characteristics between cases (death) and controls (alive) was assessed using a chi-square test and an independent t-test with a p-value of <0.05 considered as having a statistically significant difference. Multivariable binary logistic regression was used to assess a statistically significant association between the predictor variables and outcome of Severe COVID-19 (Alive Vs Death) where Adjusted Odds ratio (AOR), 95% CIs for AOR, and P-values were used for testing significance and interpretation of results.

Results

Having diabetes mellitus (AOR= 3.257, 95% CI= 1.348, 7.867, p-value=0.00), fever (AOR=0.328, 95% CI: 0.123, 0.878, p-value= 0.027) and Shortness of breath (AOR= 4.034, 95% CI= 1.481, 10.988, p-value=0.006) were found to be significant predictors of death in Severe COVID-19 patients.

Conclusions

The outcome of death in Severe COVID-19 patients is found to be associated with exposures to being diabetic and having SOB at admission. On the other hand, having a fever at admission was associated with a favorable outcome of being discharged alive.
Dry eye disease: A Canadian quality of life and productivity loss survey
Authors: Chan Clara C. , Ziai Setareh , Myageri Varun , Burns James G. , Prokopich C. Lisa
Published: October 2020

Aim

To capture the direct and indirect cost estimates of dry eye disease (DED), stratified by disease severity, in patients from Canada and to understand the impact of DED on quality of life (QoL) in this group.

Methods

A prospective, multi-centre, observational, cross-sectional study was conducted at six optometry and ophthalmology sites across Canada. Eligible patients completed a 20-minute survey on demography, general health, disease severity, QoL, and direct and indirect costs.

Results

A total of 151 patients participated in the study and 146 were included in the analysis. Mean (standard deviation [SD]) age was 49.8 (11.4) years and most patients were female (89.7%). DED was considered moderate or severe by 19.2% and 69.2% of patients, respectively. Sjögren’s syndrome was reported by 8.2% of patients. Total mean annual costs of DED were $24,331 (Canadian dollars [CAD]) per patient and increased with disease severity. Mean (SD) indirect costs for mild, moderate, and severe disease were $5,961 ($6,275), $16,525 ($11,607), and $25,485 ($22,879), respectively. Mean (SD) direct costs were $958 ($1,216), $1,303 ($1,574), and $2,766 ($7,161), respectively. QoL scores were lowest in patients with Sjögren’s syndrome and those with severe DED.

Conclusions

This study provides important insights into the negative impact of DED in a Canadian setting. Patients with severe DED reported higher direct and indirect costs and lower QoL compared with those with mild or moderate disease. Increased costs and poorer QoL were also evident for patients with DED plus Sjögren’s syndrome versus DED alone.
Role of high-dose exposure in transmission hot zones as a driver of SARS-CoV2 dynamics
Authors: Wodarz Dominik , Komarova Natalia L. , Schang Luis M.
Published: October 2020

Epidemiological data on the spread of SARS-CoV-2 in the absence and presence of various non-pharmaceutical interventions indicate that the virus is not transmitted uniformly in the population. Transmission tends to be more effective in select settings that involve exposure to relatively high viral dose, such as in crowded indoor settings, assisted living facilities, prisons, or food processing plants. To explore the effect on infection dynamics, we describe a new mathematical model where transmission can occur (i) in the community at large, characterized by low dose exposure and mostly mild disease, and (ii) in so called transmission hot zones, characterized by high dose exposure that can be associated with more severe disease. Interestingly, we find that successful infection spread can hinge upon high-dose hot zone transmission, yet the majority of infections are predicted to occur in the community at large with mild disease. This gives rise to the prediction that targeted interventions that specifically reduce virus transmission in the hot zones (but not in the community at large) have the potential to suppress overall infection spread, including in the community at large. The model can further reconcile seemingly contradicting epidemiological observations. While in some locations like California, strict stay-home orders failed to significantly reduce infection prevalence, in other locations, such as New York and several European countries, stay-home orders lead to a pronounced fall in infection levels, which remained suppressed for some months after re-opening of society. Differences in hot zone transmission levels during and after social distancing interventions can account for these diverging infection patterns. These modeling results warrant further epidemiological investigations into the role of high dose hot zone transmission for the maintenance of SARS-CoV-2 spread.
Report on COVID-19 Verification Case Study in Nine Countries Using the SIQR model
Authors: Suda Reiji
Published: October 2020

This report uses the SIQR model proposed by Takashi Odagaki to examine the epidemic trend of COVID-19 in nine major countries during February-May 2020, and to clarify the peculiar trend of infection in Japan. The SIQR model, which is an improvement on the conventional SIR model, is unique in that it allows us to theoretically clarify the epidemic phenomenon by separating the number of daily confirmed new cases by testing and the number of infecteds at large who remain untested, and also allows us to theoretically consider measures to control the epidemic. The infection control measures of each country were analyzed by dividing them into three groups according to the size of the decay (or growth) rate of infected at large (λ). The active group includes China and South Korea, the passive group includes the United States and Sweden, and the average group includes Germany, Italy, France, Spain, and Japan. China and South Korea are the countries with the best testing and quarantine systems, and South Korea in particular having managed to contain the infection without lockdown through early quarantine by thorough testing. On the other hand, the United States and Sweden do not have a well-developed inspection and quarantine system and have shown little restraint in social distancing. In the case of Japan, the following special factors may have contributed to the extreme lack of PCR testing : (1) The “4-day fever rule” established by the Ministry of Health, Labour and Welfare was strictly enforced. (2) Even after the decision to postpone the Olympics, the government continued to monopolize PCR testing for the sake of unified analysis of infection data, and the policy of expanding PCR testing by private companies was not implemented.
Cost-effectiveness of Dengue Vaccination in Puerto Rico
Authors: España Guido , Leidner Andrew J. , Waterman Stephen , Perkins T. Alex
Published: October 2020

An effective and widely used vaccine could reduce the burden of dengue virus (DENV) around the world. DENV is endemic in Puerto Rico, where the dengue vaccine CYD-TDV is currently under consideration as a control measure. CYD-TDV has demonstrated efficacy in clinical trials in vaccinees who had prior dengue infection. However, in vaccinees who had no prior dengue infection, the vaccine had a modestly elevated risk of hospitalization and severe disease. The WHO therefore recommended a strategy of pre-vaccination screening and vaccination of seropositive persons. To estimate the cost-effectiveness and benefits of this intervention (i.e., screening and vaccination of seropositive persons) in Puerto Rico, we simulated 10 years of the intervention in 9-year-olds using an agent-based model. Across the entire population, we found that 5.5% (4.6%-6.3%) of dengue hospitalizations could be averted. However, we also found that 1.6 (1.3 - 2.1) additional hospitalizations could occur for every 1,000 DENV-naïve children who were vaccinated following a false-positive test results for prior exposure. The ratio of the averted hospitalizations among all vaccinees to additional hospitalizations among DENV-naïve vaccinees was estimated to be 19 (13-24). At a base case cost of vaccination of 382 USD, we found an incremental cost-effectiveness ratio of 122,000 USD per QALY gained. Our estimates can provide information for considerations to introduce the CYD-TDV vaccine in Puerto Rico.
Pharmacological inhibition of the ALK axis elicits therapeutic potential in Consensus Molecular Subtype 1 colon cancer patients
Authors: Mazzeschi Martina , Sgarzi Michela , Romaniello Donatella , Gelfo Valerio , Cavallo Carola , Santi Spartaco , Fiorentino Michelangelo , D’Uva Gabriele , Győrffy Balázs , Palmer Ruth , Lauriola Mattia
Published: October 2020

In the last years, several efforts have been made to classify colorectal cancer (CRC) into well-defined molecular subgroups, representing the intrinsic inter-patient heterogeneity, known as Consensus Molecular Subtypes (CMSs). In this work, we performed a meta-analysis of 1700 CRC patients stratified into four CMSs. We identified a negative correlation between a high level of anaplastic lymphoma kinase (ALK) expression and relapse-free survival, exclusively in CMS1 subtype. Stemming from this observation, we tested several CMSsin vitromodels with crizotinib (CZB) or alectinib (ALC), potent ALK inhibitors, already approved for clinical use. ALK interception strongly inhibits cell proliferation already at nanomolar doses, specifically in CMS1 cell lines, while no effect was found in CMS2/3/4 groups. Furthermore,in vivoimaging identified a role for ALK in the dynamic formation of 3D spheroids, which was impaired by the pharmacological inhibition of ALK. Consistently, CZB was responsible for the dampened activation of ALK along with the downstream AKT cascade. Mechanistically, we found a specific pro-apoptotic effect of ALK inhibition in CMS1 cell lines, both in 2D and 3D. Confocal analysis suggests that inhibition in CMS1 cells enhances cell-cell adhesion when growing in 3D. In agreement with our findings, an ALK signature encompassing 65 genes statistically associated with worse relapse-free survival in CMS1 subtype. Finally, the efficacy of ALK inhibition treatment was demonstrated in patient-derived organoids. Collectively, our findings suggest that ALK inhibition may represent an attractive therapy for CRC, and CMS classification may provide a useful tool to identify patients who could benefit from this treatment. These findings offer rationale and pharmacological strategies for the treatment of CMS1 CRC.
COUP-TFI regulates diameter of the axon initial segment in the mammalian neocortex
Authors: Wu Xuanyuan , Li Haixiang , Huang Jiechang , Xiao Cheng , He Shuijin
Published: October 2020

The axon initial segment is a specialized structure that controls neuronal excitability by generating action potentials. Currently, AIS plasticity with regard to changes in length and location in response to neural activity has been extensively investigated, but how AIS diameter is regulated remains elusive. Here we report that COUP-TFI is an essential regulator of AIS diameter in both developing and adult mouse neocortex. Embryonic ablation of COUP-TFI prevented expansion of AIS diameter that occurs during postnatal development in layer II/III pyramidal cells of the mouse motor cortex, thereby leading to an impairment of action potential generation. Inactivation of COUP-TFI in adult neurons also led to reduced AIS diameter and impaired action potential generation. In contrast to different developmental stages, single-cell ablation and global ablation produced opposite effects on spontaneous network in COUP-TFI-deficient neurons. Further, mice exhibited less anxiety-like behaviors after postnatal inactivation of COUP-TFI induced by tamoxifen. Our results demonstrate that COUP-TFI is indispensable for both expansion and maintenance of AIS diameter and that a change in AIS diameter fine-tunes synaptic inputs through a metaplasticity mechanism in the adult neocortex.
Schengen-pathway controls spatially separated and chemically distinct lignin deposition in the endodermis
Authors: Reyt Guilhem , Ramakrishna Priya , Salas-González Isai , Fujita Satoshi , Love Ashley , Tiemessen David , Lapierre Catherine , Morreel Kris , Polanco Monica Calvo , Flis Paulina , Geldner Niko , Boursiac Yann , Boerjan Wout , George Michael W. , Castrillo Gabriel , Salt David E.
Published: October 2020

Lignin is a complex polymer precisely deposited in the cell wall of specialised plant cells, where it provides essential cellular functions. Plants coordinate timing, location, abundance and composition of lignin deposition in response to endogenous and exogenous cues. In roots, a fine band of lignin, the Casparian strip encircles endodermal cells. This forms an extracellular barrier to solutes and water and plays a critical role in maintaining nutrient homeostasis. A signalling pathway senses the integrity of this diffusion barrier and can induce over-lignification to compensate for barrier defects. Here, we report that activation of this endodermal sensing mechanism triggers a transcriptional reprogramming strongly inducing the phenylpropanoid pathway and immune signaling. This leads to deposition of compensatory lignin that is chemically distinct from Casparian strip lignin. We also report that a complete loss of endodermal lignification drastically impacts mineral nutrients homeostasis and plant growth.
Single-nucleus transcriptome analysis reveals cell type-specific molecular signatures across reward circuitry in the human brain
Authors: Tran Matthew N. , Maynard Kristen R. , Spangler Abby , Collado-Torres Leonardo , Sadashivaiah Vijay , Tippani Madhavi , Barry Brianna K. , Hancock Dana B. , Hicks Stephanie C. , Kleinman Joel E. , Hyde Thomas M. , Martinowich Keri , Jaffe Andrew E.
Published: October 2020

Single cell/nucleus technologies are powerful tools to study cell type-specific expression in the human brain, but most large-scale efforts have focused on characterizing cortical brain regions and their constituent cell types. However, additional brain regions - particularly those embedded in basal ganglia and limbic circuits - play important roles in neuropsychiatric disorders and addiction, suggesting a critical need to better understand their molecular characteristics. We therefore created a single-nucleus RNA-sequencing (snRNA-seq) resource across five human brain regions (hippocampus, HPC; dorsolateral prefrontal cortex, DLPFC; subgenual anterior cingulate cortex, sACC; nucleus accumbens, NAc; and amygdala, AMY), with emphasis on the NAc and AMY, given their involvement in reward signaling and emotional processing. We identified distinct and potentially novel neuronal subpopulations, which we validated by smFISH for various subclasses of NAc interneurons and medium spiny neurons (MSNs). We additionally benchmarked these datasets against published datasets for corresponding regions in rodent models to define cross-species convergence and divergence across analogous cell subclasses. We characterized the transcriptomic architecture of regionally-defined neuronal subpopulations, which revealed strong patterns of similarities in specific neuronal subclasses across the five profiled regions. Finally, we measured genetic associations between risk for psychiatric disease and substance use behaviors with each of the regionally-defined cell types. This analysis further supported NAc and AMY involvement in risk for psychiatric illness by implicating specific neuronal subpopulations, and highlighted potential involvement of an MSN population associated with stress signaling in genetic risk for substance use.
Haploid, diploid, and pooled exome capture recapitulate features of biology and paralogy in two non-model tree species
Authors: Lind Brandon , Lu Mengmeng , Vidakovic Dragana Obreht , Singh Pooja , Booker Tom , Yeaman Sam , Aitken Sally
Published: October 2020

Despite their suitability for studying evolution, many conifer species have large and repetitive giga-genomes (16-31Gbp) that create hurdles to producing high coverage SNP datasets that captures diversity from across the entirety of the genome. Due in part to multiple ancient whole genome duplication events, gene family expansion and subsequent evolution withinPinaceae, false diversity from the misalignment of paralog copies create further challenges in accurately and reproducibly inferring evolutionary history from sequence data. Here, we leverage the cost-saving benefits of pool-seq and exome-capture to discover SNPs in two conifer species, Douglas-fir (Pseudotsuga menziesiivar.menziesii(Mirb.) Franco,Pinaceae) and jack pine (Pinus banksianaLamb.,Pinaceae). We show, using minimal baseline filtering, that allele frequencies estimated from pooled individuals show a strong positive correlation with those estimated by sequencing the same population as individuals (r > 0.948), on par with such comparisons made in model organisms. Further, we highlight the use of haploid megagametophyte tissue in identifying sites that are likely due to misaligned paralogs. Together with additional minor filtering, we show that it is possible to remove many of the loci with large frequency estimate discrepancies between individual and pooled sequencing approaches, improving the correlation further (r > 0.973). Our work addresses bioinformatic challenges in non-model organisms with large and complex genomes, highlights the use of megagametophyte tissue for the identification of paralog sites when sequencing large numbers of populations, and suggests the combination of pool-seq and exome capture to be robust for further evolutionary hypothesis testing in these systems.
Genetic Analysis of Methyl Anthranilate, Mesifurane, Linalool and Other Flavor Compounds in Cultivated Strawberry (Fragaria×ananassa)
Authors: Barbey Christopher R. , Hogshead Maxwell H. , Harrison Benjamin , Schwartz Anne E. , Verma Sujeet , Oh Youngjae , Lee Seonghee , Folta Kevin M. , Whitaker Vance M.
Published: October 2020

The cultivated strawberry (Fragaria×ananassa) is an economically important fruit crop that is intensively bred for improved sensory qualities. The diversity of fruit flavors and aromas in strawberry result mainly from the interactions of sugars, acids, and volatile organic compounds (VOCs) that are derived from diverse biochemical pathways influenced by the expression of many genes. This study integrates multi-omics analyses to identify QTL and candidate genes for multiple aroma compounds in a complex strawberry breeding population. Novel fruit volatile QTL were discovered for methyl anthranilate, methyl 2-hexenoate, methyl 2-methylbutyrate, mesifurane, and a shared QTL on Chr 3 was found for nine monoterpene and sesquiterpene compounds, including linalool, 3-carene, β-phellandrene, α-limonene, linalool oxide, nerolidol, α-caryophellene, α-farnesene, and β-farnesene. Fruit transcriptomes from a subset of sixty-four individuals were used to support candidate gene identification. For methyl esters including the grape-like methyl anthranilate, a novelANTHANILIC ACID METHYL TRANSFERASE–like gene was identified. Two mesifurane QTL correspond with the known biosynthesis geneO-METHYL TRANSFERASE 1and a novelFURANEOL GLUCOSYLTRANSFERASE. The shared terpene QTL contains multiple fruit-expressed terpenoid pathway-related genes includingNEROLIDOL SYNTHASE 1(FanNES1). The abundance of linalool and other monoterpenes is partially governed by a co-segregating expression-QTL (eQTL) forFanNES1transcript variation, and there is additional evidence for quantitative effects from other terpenoid-pathway genes in this narrow genomic region. These QTL present new opportunities in breeding for improved flavor in commercial strawberry.
Transcribed germline-limited coding sequences inOxytricha trifallax
Authors: Miller Richard V. , Neme Rafik , Clay Derek M. , Pathmanathan Jananan S. , Lu Michael W. , Yerlici V. Talya , Khurana Jaspreet S. , Landweber Laura F.
Published: October 2020

The germline-soma divide is a fundamental distinction in developmental biology, and different genes are expressed in germline and somatic cells throughout metazoan life cycles. Ciliates, a group of microbial eukaryotes, exhibit germline-somatic nuclear dimorphism within a single cell with two different genomes. The ciliateOxytricha trifallaxundergoes massive RNA-guided DNA elimination and genome rearrangement to produce a new somatic macronucleus (MAC) from a copy of the germline micronucleus (MIC). This process eliminates noncoding DNA sequences that interrupt genes and also deletes hundreds of germline-limited open reading frames (ORFs) that are transcribed during genome rearrangement. Here, we update the set of transcribed germline-limited ORFs (TGLOs) inO. trifallax. We show that TGLOs tend to be expressed during nuclear development and then are absent from the somatic MAC. We also demonstrate that exposure to synthetic RNA can reprogram TGLO retention in the somatic MAC and that TGLO retention leads to transcription outside the normal developmental program. These data suggest that TGLOs represent a group of developmentally regulated protein coding sequences whose gene expression is terminated by DNA elimination.
DUBStepR: correlation-based feature selection for clustering single-cell RNA sequencing data
Authors: Ranjan Bobby , Sun Wenjie , Park Jinyu , Mishra Kunal , Xie Ronald , Alipour Fatemeh , Singhal Vipul , Schmidt Florian , Joanito Ignasius , Rayan Nirmala Arul , Gek Liang Lim Michelle , Prabhakar Shyam
Published: October 2020

Feature selection (marker gene selection) is widely believed to improve clustering accuracy, and is thus a key component of single cell clustering pipelines. However, we found that the performance of existing feature selection methods was inconsistent across benchmark datasets, and occasionally even worse than without feature selection. Moreover, existing methods ignored information contained in gene-gene correlations. We therefore developed DUBStepR (Determining theUnderlyingBasis usingStepwiseRegression), a feature selection algorithm that leverages gene-gene correlations with a novel measure of inhomogeneity in feature space, termed the Density Index (DI). Despite selecting a relatively small number of genes, DUBStepR substantially outperformed existing single-cell feature selection methods across diverse clustering benchmarks. In a published scRNA-seq dataset from sorted monocytes, DUBStepR sensitively detected a rare and previously invisible population of contaminating basophils. DUBStepR is scalable to over a million cells, and can be straightforwardly applied to other data types such as single-cell ATAC-seq. We propose DUBStepR as a general-purpose feature selection solution for accurately clustering single-cell data.
High contrast probe cleavage detection on porous silicon biosensors via quantum dot labeled DNA probes
Authors: Layouni Rabeb , Dubrovsky Michael , Bao Mengdi , Chung Haejun , Du Ke , Boriskina Svetlana V. , Weiss Sharon M. , Vermeulen Diedrik
Published: October 2020

Using porous silicon (PSi) interferometer sensors, we show the first experimental implementation of the high contrast probe cleavage detection (HCPCD) mechanism. HCPCD makes use of dramatic optical signal amplification caused by cleavage of high-contrast nanoparticle labels on probes instead of the capture of low-index biological molecules. An approximately 2 nm reflectance peak shift was detected after cleavage of DNA-quantum dot probes from the PSi surface via exposure to a 12.5 nM DNase enzyme solution for 2 hrs. This signal change is 20 times greater than the resolution of the spectrometer used for the interferometric measurements, and the interferometric measurements agree with the interferometric response predicted by simulations and fluorescence measurements. These proof of principle experiments show a clear path to real-time, highly sensitive and inexpensive point-of-care readout for a broad range of biological diagnostic assays that generate signal via nucleic acid cleavage.
Structural basis of the human Scribble-Vangl2 association in health and disease
Authors: How Jing Yuan , Stephens Rebecca K. , Lim Krystle Y.B. , Humbert Patrick O. , Kvansakul Marc
Published: October 2020

Scribble is a critical cell polarity regulator that has been shown to work as either an oncogene or tumor suppressor in a context dependent manner, and also impacts cell migration, tissue architecture and immunity. Mutations in Scribble lead to neural tube defects in mice and humans, which has been attributed to a loss of interaction with the planar cell polarity regulator Vangl2. We show that the Scribble PDZ domains 1, 2 and 3 are able to interact with the C-terminal PDZ binding motif of Vangl2 and have now determined crystal structures of these Scribble PDZ domains bound to the Vangl2 peptide. Mapping of mammalian neural tube defect mutations reveal that mutations located distal to the canonical PDZ domain ligand binding groove can not only ablate binding to Vangl2 but also disrupt binding to multiple other signaling regulators. Our findings suggest that PDZ-associated neural tube defect mutations in Scribble may not simply act in a Vangl2 dependent manner but as broad-spectrum loss of function mutants by disrupting the global Scribble-mediated interaction network.