bluuebunny/crossref_metadata_2025 huggingface dataset:
Racial and Ethnic Differences in Prescription Filling After Discharge From an Urban Pediatric Emergency Department
Authors: Berkowitz Deena , Breslin Kristen , Croskey Annabelle , Badolato Gia , Goyal Monika K.
Published: June 2020

Objective

The aim of this study was to measure racial/ethnic differences in prescription filling among children prescribed with outpatient antibiotics from the emergency department (ED).

Methods

This study is a retrospective cohort study of ED visits among children (0–21 years) from January 1 to March 31, 2018, during which oral antibiotics were prescribed. We measured the proportion of filled prescriptions in aggregate and by patient race/ethnicity. We performed multivariable logistic regression to identify patient and visit-level factors associated with prescription filling. Secondarily, we measured differences in ED revisits by prescription filling.

Results

A total of 2881 participants were enrolled. A total of 66.3% (95% confidence interval, 64.5–68.0) of prescriptions were filled. Prescription filling varied by race/ethnicity; these are as follows: 77.3% non-Hispanic (NH) white, 73.5% NH black, 51.5% Hispanic, and 51.3% others (P < 0.0001). After adjustment for patient and visit-level characteristics, Hispanic children (adjusted odds ratio [aOR], 0.5 [0.3–0.9]) and children of other racial/ethnic groups (aOR, 0.5 [0.3–0.8]) had lower odds of prescription filling in comparison to NH white children. Interpreter use (aOR, 0.5 [0.4–0.6]) and uninsured status (aOR, 0.4 [0.3–0.5]) were additional independent risk factors associated with lower odds of prescription filling. There were no differences in the 72-hour revisit rates between those who filled their prescriptions and those who did not.

Conclusions

A third of antibiotic prescriptions for bacterial infections in the ED are unfilled. Hispanic children and children of other racial/ethnic groups have lower rates of prescription filling compared with NH white children. Interpreter use and uninsured status also have lower rates of prescription filling. Barriers to prescription filling should be explored further to help reduce racial and ethnic disparities in the provision of health care.
Fibularis Intersection Syndrome
Authors: Monsour Marc , Sangha Harpreet , Farag Jordan , Mittal Nimish
Published: June 2020

Running is a common cause of foot and ankle injuries. Accurate diagnosis is important for appropriate management to resolve the issue. For clarity of diagnoses, the physician should be able to perform a thorough physical examination in conjunction with point-of-care ultrasound. The authors report a case study of a young male runner with lateral ankle pain. Based on clinical assessment and point-of-care ultrasound, a diagnosis of fibularis intersection syndrome was proposed. This type of injury can be treated with graded eccentric loading of fibularis tendons and proprioceptive exercises. This case report highlights the importance of point-of-care ultrasound to determine the appropriate diagnosis and management.
Outcomes of Volume Replacement Oncoplastic Breast-Conserving Surgery Using Chest Wall Perforator Flaps: Comparison with Volume Displacement Oncoplastic Surgery and Total Breast Reconstruction
Authors: Schaverien Mark V. , Kuerer Henry M. , Caudle Abigail S. , Smith Benjamin D. , Hwang Rosa F. , Robb Geoffrey L.
Published: June 2020

Background:

Volume replacement oncoplastic breast-conserving surgery (VR-OBCS) uses islanded or pedicled chest wall fasciocutaneous perforator flaps from outside of the breast footprint to replace the volume that has been excised during lumpectomy, extending the options for breast conservation to patients who may otherwise require mastectomy. This study compares outcomes for VR-OBCS with both standard volume displacement oncoplastic breast-conserving surgery (VD-OBCS) and mastectomy with immediate total breast reconstruction (TBR).

Methods:

A retrospective cohort study was conducted; demographic data, clinicopathologic factors, surgical details, and postoperative events were collected until patients had completed their reconstructions. Variables were compared using the t test and analysis of variance test, or chi-square analysis and Fisher’s exact test, as appropriate.

Results:

Ninety-seven consecutive patients (109 immediate breast reconstruction procedures) were included: 43 percent underwent standard VD-OBCS procedures, 35 percent underwent mastectomy with immediate TBR, and VR-OBCS techniques were used in 22 percent, of which only one patient required a delayed procedure for symmetry. Mean whole tumor size was similar in the VR-OBCS and TBR groups and was significantly higher than for the VD-OBCS group (p < 0.05). Overall rate of complications affecting the breast area (p < 0.001), need for additional surgery to either breast (p < 0.001), and time to reconstruction completion (p < 0.001) were significantly higher in the TBR group.

Conclusions:

VR-OBCS extends the options for breast conservation to many patients that would otherwise require mastectomy. The complication rate is lower, fewer procedures are necessary, and less time is required to complete the reconstruction when compared with mastectomy and immediate TBR.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Trends in Medicare Reimbursement for Reconstructive Plastic Surgery Procedures: 2000 to 2019
Authors: Gupta Nikita , Haglin Jack M. , Marostica Chance W. , Thornburg Danielle A. , Casey William J.
Published: June 2020

Background:

An understanding of financial trends is important to advance agreeable reimbursement models in plastic surgery. This study aimed to evaluate trends in Medicare reimbursement rates for the 20 most commonly billed reconstructive plastic surgery procedures from 2000 to 2019.

Methods:

The Centers for Medicare and Medicaid Services Physician and Other Supplier Public Use File was used to identify the 20 reconstructive procedures most commonly billed to Medicare by plastic surgeons in 2016. Reimbursement data were extracted from The Physician Fee Schedule Look-Up Tool from the Centers for Medicare and Medicaid Services for each CPT code. Monetary data were adjusted for inflation to 2019 U.S. dollars. Average annual and total percentage changes in reimbursement were calculated based on these adjusted trends.

Results:

The average adjusted reimbursement for all procedures decreased by 14.0 percent from 2000 to 2019. The greatest mean decrease was observed in complex wound repair of the scalp, arms, or legs (−33.2 percent). The only procedure with an increased adjusted reimbursement rate was layer-closure of the scalp, axillae, trunk, and/or extremities (6.5 percent). From 2000 to 2019, the adjusted reimbursement rate for all procedures decreased by an average of 0.8 percent annually.

Conclusions:

This is the first comprehensive study evaluating trends in Medicare reimbursement in plastic surgery. When adjusted for inflation, Medicare reimbursement for the included procedures has steadily decreased from 2000 to 2019. Increased consideration of these trends will be important for U.S. policymakers, hospitals, and surgeons to ensure continued access to meaningful reconstructive plastic surgery care.
Current Trends in the Use of Social Media by Plastic Surgeons
Authors: Cho Min-Jeong , Li Alexander Y. , Furnas Heather J. , Rohrich Rod J.
Published: June 2020

Background:

As social media continue to be widely used, understanding the current trend in social media use by plastic surgeons will help determine how the specialty can better harness its power and respect its risks. In this study, the authors performed a survey study of trainees, candidates, and members of the American Society of Plastic Surgeons to determine current use and consensus on social media in plastic surgery.

Methods:

An electronic survey was sent to plastic surgery trainees, candidates, and members of the American Society of Plastic Surgeons using SurveyMonkey. Demographic data, social media use patterns, and views on social media use were collected.

Results:

When compared with salaried surgeons, private practitioners used social media for the promotion of their practice, such as patient acquisition (74.3 percent versus 28.3 percent) and branding (61 percent versus 21.7 percent). The majority of nonusers felt social media was too time consuming and susceptible to breach of patient privacy. The majority of social media users agreed that acceptable use included before-and-after photographs, video testimonials, and patient reviews. Both social media users and nonusers alike agreed that plastic surgery residents should receive training on social media.

Conclusions:

This study showed that a majority of plastic surgeons use social media to brand their practice, attract patients, and educate the public. Without engaging in this valuable tool, plastic surgeons’ voices will be lost in the conversation. To use social media to their greatest potential, this specialty needs to begin formal training in the proper and ethical use of social media.
An HIV-1 Nef genotype that diminishes immune control mediated by protective human leucocyte antigen alleles
Authors: Mwimanzi Francis , Ngare Isaac , Toyoda Mako , Mori Masahiko , Mann Jaclyn , Ndung’u Thumbi , Goulder Phillip , Ueno Takamasa
Published: June 2020

Objectives:

Certain human leucocyte antigen (HLA)-B alleles (protective alleles) associate with durable immune control of HIV-1, but with substantial heterogeneity in the level of control. It remains elusive whether viral factors including Nef-mediated immune evasion function diminish protective allele effect on viral control.

Design:

The naturally occurring non-Ser variant at position 9 of HIV-1 subtype C Nef has recently exhibited an association with enhanced HLA-B downregulation function and decreased susceptibility to recognition by CD8+ T cells. We therefore hypothesized this Nef genotype leads to diminished immune control mediated by protective HLA alleles.

Methods:

Nef sequences were isolated from HIV-1 subtype C-infected patients harboring protective alleles and several Nef functions including downregulation of HLA-A, HLA-B, CD4, and SERINC5 were examined. Association between Nef non-Ser9 and plasma viral load was examined in two independent South African and Botswanan treatment-naïve cohorts.

Results:

Nef clones isolated from protective allele+ individuals encoding Nef non-Ser9 variant exhibited greater ability to downregulate HLA-B when compared with the Ser9 variant, while other Nef functions including HLA-A, CD4, and SERINC5 downregulation activity were unaltered. By analyzing a cohort of South African participants chronically infected with subtype C HIV-1, Nef non-Ser9 associated with higher plasma viral load in patients harboring protective alleles. Corroboratively, the Nef non-Ser9 correlated with higher plasma viral load in an independent cohort in Botswana.

Conclusion:

Taken together, our study identifies the Nef genotype, non-Ser9 that subverts host immune control in HIV-1 subtype C infection.
Low hepatitis C virus reinfection rate despite ongoing risk following universal access to direct-acting antiviral therapy among people living with HIV
Authors: Hosseini-Hooshyar Samira , Martinello Marianne , Yee Jasmine , Read Phillip , Baker David , Post Jeffrey J. , Finlayson Robert , Bloch Mark , Doyle Joseph S. , Shaw David , Hellard Margaret , Petoumenos Kathy , Carson Joanne , Dore Gregory J. , Matthews Gail V.
Published: June 2020

Objective(s):

To evaluate changes in injecting and sexual risk behaviours, and hepatitis C virus (HCV) reinfection incidence among people with HIV/HCV coinfection following unrestricted access to direct-acting antiviral therapy in Australia.

Design:

Prospective observational cohort study (2014–2018).

Methods:

Among people enrolled in the Control and Elimination of HCV from HIV-infected individuals within Australia study, changes in injecting and sexual behaviour were evaluated, including injecting drug use (IDU) in the last 6 months and last month, frequency of IDU and equipment sharing, condom-less anal intercourse with casual male partner(s), and group sex. HCV reinfection incidence was evaluated with follow-up through May 2018.

Results:

Overall, 272 HIV/HCV antibody-positive participants [median age; 50 years, 96% male, 83% identified as gay and bisexual men (GBM)] had behavioural data at enrolment and follow-up (median 2.91 years) available for analysis. The proportion reporting IDU in the last 6 months remained stable from enrolment (35%) to follow-up (39%). Among GBM, the proportion reporting condom-less anal intercourse with casual partner(s) at enrolment (48%) and follow-up (46%) was also similar. Reinfection was detected in five individuals (all GBM) during total follow-up of 474 person-years for an overall incidence of 1.05 per 100 person-years (95% confidence interval, 0.44–2.53).

Conclusion:

No change was observed in levels of injecting or sexual risk behaviour for HCV infection following unrestricted access to direct-acting antiviral therapy in an Australian HIV/HCV cohort. Incidence of HCV reinfection was low potentially reflecting high levels of treatment coverage within this population. Continued screening and rapid retreatment of reinfection will be required to maintain progress towards elimination.
Influence of Primary Health Care Physicians' Perceived Overqualification on Turnover Intention in China
Authors: Li Wenjun , Xu Ailin , Lu Mengqing , Lin Guohua , Wo Tian , Xi Xiaoyu
Published: June 2020

Background:

With the aging population and increasing prevalence of chronic disease, the number of primary health care physicians in China is inadequate and physicians' turnover intention is too high.

Objective:

To analyze the status of primary health care physicians' turnover intention in China and the relationship between physicians' perceived overqualification and their turnover intention.

Methods:

With multistage stratified sampling, we randomly selected 1456 primary health care physicians as study subjects. Information on personal characteristics, job satisfaction, working pressure, turnover intention, and perceived overqualification was collected. The data were analyzed using descriptive statistics and multiple regression analysis.

Results:

We found that primary health care physicians in China have high turnover intention and perceived overqualification is positively related to turnover intention.

Conclusion:

Government and primary health care may address perceived overqualification to reduce physicians' turnover intention.
Ultrasound First for Pediatric Patients in an Electrodiagnostic Laboratory
Authors: Rardin Benjamin P. , Verenes Michael P. , Cartwright Michael S.
Published: June 2020

Purpose:

Electrodiagnostic testing is often critical for the diagnosis of neuromuscular disease, but it can be challenging in the pediatric population because of poor tolerance. This study evaluates an ultrasound-first approach as a means of reducing the number of electrodiagnostic tests (nerves stimulated and muscles sampled) in the pediatric population.

Methods:

A retrospective analysis of 21 pediatric patients who underwent ultrasound before electrodiagnostic testing as part of a quality-improvement project was conducted and compared with an age-matched control group of 84 patients.

Results:

The ultrasound-first group underwent significantly fewer muscle samplings (P = 0.0002) and overall number of electrodiagnostic tests (P = 0.0010) than the control group. The ultrasound-first group also underwent fewer nerve stimulations, which approached statistical significance (P = 0.0600).

Conclusions:

Using ultrasound first in the electrodiagnostic laboratory in pediatric patients could reduce the number of electrodiagnostic tests needed to arrive at a diagnosis.
KEAP1, a cysteine-based sensor and a drug target for the prevention and treatment of chronic disease
Authors: Dayalan Naidu Sharadha , Dinkova-Kostova Albena T.
Published: June 2020

Redox imbalance and persistent inflammation are the underlying causes of most chronic diseases. Mammalian cells have evolved elaborate mechanisms for restoring redox homeostasis and resolving acute inflammatory responses. One prominent mechanism is that of inducing the expression of antioxidant, anti-inflammatory and other cytoprotective proteins, while also suppressing the production of pro-inflammatory mediators, through the activation of transcription factor nuclear factor-erythroid 2 p45-related factor 2 (NRF2). At homeostatic conditions, NRF2 is a short-lived protein, which avidly binds to Kelch-like ECH-associated protein 1 (KEAP1). KEAP1 functions as (i) a substrate adaptor for a Cullin 3 (CUL3)-based E3 ubiquitin ligase that targets NRF2 for ubiquitination and proteasomal degradation, and (ii) a cysteine-based sensor for a myriad of physiological and pharmacological NRF2 activators. Here, we review the intricate molecular mechanisms by which KEAP1 senses electrophiles and oxidants. Chemical modification of specific cysteine sensors of KEAP1 results in loss of NRF2-repressor function and alterations in the expression of NRF2-target genes that encode large networks of diverse proteins, which collectively restore redox balance and resolve inflammation, thus ensuring a comprehensive cytoprotection. We focus on the cyclic cyanoenones, the most potent NRF2 activators, some of which are currently in clinical trials for various pathologies characterized by redox imbalance and inflammation.
An miRNA fingerprint using neural-enriched extracellular vesicles from blood plasma: towards a biomarker for amyotrophic lateral sclerosis/motor neuron disease
Authors: Banack Sandra Anne , Dunlop Rachael Anne , Cox Paul Alan
Published: June 2020

Biomarkers for amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) are currently not clinically available for disease diagnosis or analysis of disease progression. If identified, biomarkers could improve patient outcomes by enabling early intervention and assist in the determination of treatment efficacy. We hypothesized that neural-enriched extracellular vesicles could provide microRNA (miRNA) fingerprints with unequivocal signatures of neurodegeneration. Using blood plasma from ALS/MND patients and controls, we extracted neural-enriched extracellular vesicle fractions and conducted next-generation sequencing and qPCR of miRNA components of the transcriptome. We here report eight miRNA sequences which significantly distinguish ALS/MND patients from controls in a replicated experiment using a second cohort of patients and controls. miRNA sequences from patient blood samples using neural-enriched extracellular vesicles may yield unique insights into mechanisms of neurodegeneration and assist in early diagnosis of ALS/MND.
SARS-CoV-2 titers in wastewater foreshadow dynamics and clinical presentation of new COVID-19 cases
Authors: Wu Fuqing , Xiao Amy , Zhang Jianbo , Moniz Katya , Endo Noriko , Armas Federica , Bonneau Richard , Brown Megan A , Bushman Mary , Chai Peter R , Duvallet Claire , Erickson Timothy B , Foppe Katelyn , Ghaeli Newsha , Gu Xiaoqiong , Hanage William P , Huang Katherine H , Lee Wei Lin , Matus Mariana , McElroy Kyle A , Nagler Jonathan , Rhode Steven F , Santillana Mauricio , Tucker Joshua A , Wuertz Stefan , Zhao Shijie , Thompson Janelle , Alm Eric J
Published: June 2020

Current estimates of COVID-19 prevalence are largely based on symptomatic, clinically diagnosed cases. The existence of a large number of undiagnosed infections hampers population-wide investigation of viral circulation. Here, we use longitudinal wastewater analysis to track SARS-CoV-2 dynamics in wastewater at a major urban wastewater treatment facility in Massachusetts, between early January and May 2020. SARS-CoV-2 was first detected in wastewater on March 3. Viral titers in wastewater increased exponentially from mid-March to mid-April, after which they began to decline. Viral titers in wastewater correlated with clinically diagnosed new COVID-19 cases, with the trends appearing 4-10 days earlier in wastewater than in clinical data. We inferred viral shedding dynamics by modeling wastewater viral titers as a convolution of back-dated new clinical cases with the viral shedding function of an individual. The inferred viral shedding function showed an early peak, likely before symptom onset and clinical diagnosis, consistent with emerging clinical and experimental evidence. Finally, we found that wastewater viral titers at the neighborhood level correlate better with demographic variables than with population size. This work suggests that longitudinal wastewater analysis can be used to identify trends in disease transmission in advance of clinical case reporting, and may shed light on infection characteristics that are difficult to capture in clinical investigations, such as early viral shedding dynamics.
Molecular characterization of pathogenic African trypanosomes in biting flies and camels in surra-endemic areas outside the tsetse fly belt in Kenya
Authors: Getahun Merid N. , Villinger Jandouwe , Bargul Joel L. , Orone Abel , Ngiela John , Ahuya Peter O. , Muema Jackson M. , Saini Rajinder K. , Torto Baldwyn , Masiga Daniel K.
Published: June 2020

Background

African animal trypanosomosis is becoming prevalent beyond its traditionally defined geographical boundaries and is a threat to animals beyond the tsetse belts in and outside Africa. However, knowledge of infections with clinically important trypanosome species and their diversity among field-collected hematophagous biting flies and domestic animals is limited mainly to tsetse and their mammalian hosts in tsetse-infested areas. This study aimed to examine the presence of trypanosomes in both biting flies and domestic animals outside the tsetse belt in northern Kenya, potential mechanical vector species, and their host-feeding profiles.

Methods

We screened for pathogenic African trypanosomes in blood samples from domestic animals and field-trapped flies by microscopy and sequencing of internal transcribed spacer (ITS1) gene PCR products. We sequenced kinetoplast maxicircle genes to confirmTrypanosoma bruceidetection and the RoTat 1.2 and kinetoplast minicircle genes to differentiate type-A and type-BTrypanosoma evansi, respectively. Further, we identified the hosts that field-trapped flies fed on by PCR-HRM and sequencing of 16S rRNA genes.

Results

Hippobosca camelina,Stomoxys calcitrans, Tabanusspp., andPangonia rueppelliiare potential vectors of trypanosomes outside the tsetse belt in Marsabit County, northern Kenya. We identifiedTrypanosoma spp., includingTrypanosoma vivax,T. evansi,T. brucei, andT. congolensein these biting flies as well as in camels (Camelus dromedarius). Trypanosomes detected varied from single up to three trypanosome species inH. camelinaand camels in areas where no tsetse flies were trapped. Similar trypanosomes were detected inGlossina pallidipescollected from a tsetse-infested area in Shimba Hills, coastal Kenya, showing the wide geographic distribution of trypanosomes. Furthermore, we show that these biting flies acquired blood meals from camels, cattle, goats, and sheep. Phylogenetic analysis revealed diverseTrypanosomaspp. associated with variations in virulence and epidemiology in camels, which suggests that camel trypanosomosis may be due to mixed trypanosome infections rather than only surra (T. evansi), as previously thought.
Deep convolutional approaches for the analysis of Covid-19 using chest X-Ray images from portable devices
Authors: de Moura Joaquim , Ramos Lucía , Vidal Plácido L. , Cruz Milena , Abelairas Laura , Castro Eva , Novo Jorge , Ortega Marcos
Published: June 2020

The recent human coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been declared as a global pandemic on 11 March 2020 by the World Health Organization. Given the effects of COVID-19 in pulmonary tissues, chest radiography imaging plays an important role for the screening, early detection and monitoring of the suspected individuals. Hence, as the pandemic of COVID-19 progresses, there will be a greater reliance on the use of portable equipment for the acquisition of chest X-Ray images due to its accessibility, widespread availability and benefits regarding to infection control issues, minimizing the risk of cross contamination. This work presents novel fully automatic approaches specifically tailored for the classification of chest X-Ray images acquired by portable equipment into 3 different clinical categories: normal, pathological and COVID-19. For this purpose, two complementary deep learning approaches based on a densely convolutional network architecture are herein presented. The joint response of both approaches allows to enhance the differentiation between patients infected with COVID-19, patients with other diseases that manifest characteristics similar to COVID-19 and normal cases. The proposed approaches were validated over a dataset provided by the Radiology Service of the Complexo Hospitalario Universitario A Coruña (CHUAC) specifically retrieved for this research. Despite the poor quality of chest X-Ray images that is inherent to the nature of the portable equipment, the proposed approaches provided satisfactory results, allowing a reliable analysis of portable radiographs, to support the clinical decision-making process.
On the secondary waves of the pandemic launched in Iran and other countries
Authors: Kovriguine D. , Nikitenkova S.
Published: June 2020

In the last decade of April 2020, the second epidemic wave began in Iran. If judging by the dynamics of total cases, the birth of this second wave coincides practically with the maximum growth rate of the primary epidemic started in Iran from the very beginning of 2020. Today, the secondary epidemic wave almost doubles the peak of the primary. The new epidemic wave grows rapidly and unpredictably. Also, we admit that the secondary epidemic waves are already getting started in other countries.
Comparison of Care Utilization and Medical Institutional Death among Older Adults by Home Care Facility Type: A Retrospective Cohort Study in Fukuoka, Japan
Authors: Kim Sung-A , Babazono Akira , Jamal Aziz , Li Yunfei , Liu Ning
Published: June 2020

Objectives

We compared the care services use and medical institutional deaths among older adults across four home care facility types.

Design

This was a retrospective cohort study.

Setting

We used administrative claims data from April 2014 to March 2017.

Participants

We included 18,347 residents of Fukuoka Prefecture, Japan, who received home care during the period, and aged ≥75 years with certified care needs of at least level 3. Participants were categorized based on home care facility use (i.e., general clinics, Home Care Support Clinics/Hospitals (HCSCs), enhanced HCSCs with beds, and enhanced HCSCs without beds).

Primary and secondary outcome measures

We used generalized linear regression models to estimate care utilization and the incidence of medical institutional death, as well as the potential influence of sex, age, care needs level, and Charlson comorbidity index as risk factors.

Results

The results of generalized linear models showed the inpatient days were 53.3, 67.4, 63.9, and 72.6 for users of enhanced HCSCs with beds, enhanced HCSCs without beds, HCSCs, and general clinics, respectively. Correspondingly, the numbers of home care days were 64.0, 51.6, 57.9, and 28.4. Our multivariable logistic regression model estimated medical institutional death rate among participants who died during the study period (n = 9919) was 2.32 times higher (P<0.001) for general clinic users than enhanced HCSCs with beds users (relative risks=1.69, P<0.001).

Conclusions

Participants who used enhanced HCSCs with beds had a relatively low inpatient utilization, medical institutional deaths, and a high utilization of home care and home-based end-of-life care. Findings suggest enhanced HCSCs with beds could reduce hospitalization days and medical institutional deaths. Our study warrants further investigations of home care as part of community-based integrated care.

Trial registration

This study was approved by the Kyushu University Institutional Review Board for Clinical Research (Approval No. 20209).

Strengths and limitations of this study

This was a retrospective cohort study including data on 18,347 individuals.

This study was designed to suggest the kind of healthcare system that will be needed in the future in aging societies by examining the associations of the type of home care provision system with end-of-life care and place of death for older adults.

We calculated the number of years that participants lived during the study period and estimated the annual utilization rates per person-year of observation.

This study was conducted using data only on residents of Fukuoka Prefecture in Japan, which limits the generalizability of our findings

There were no clinical data for individual participants because this study focused on the types of healthcare facilities that provide home care.
Modelling the impact of lockdown easing measures on cumulative COVID-19 cases and deaths in England
Authors: Ziauddeen H , Subramaniam N , Gurdasani D
Published: June 2020

Background

As countries begin to ease the lockdown measures instituted to control the COVID-19 pandemic, there is a risk of a resurgence of the pandemic, and early reports of this are already emerging from some countries. Unlike many other countries, the UK started easing lockdown in England when levels of community transmission were still high, and this could have a major impact on case numbers and deaths. However thus far, the likely impacts of easing restrictions at this point in the pandemic have not been quantified. Using a Bayesian model, we assessed the potential impacts of successive lockdown easing measures in England, focussing on scenarios where the reproductive number (R) remains ≤1 in line with the UK government’s stated aim.

Methods

We developed a Bayesian model to infer incident cases and R in England, from incident death data from the Office of National Statistics. We then used this to forecast excess cases and deaths in multiple plausible scenarios in which R increases at one or more time points, compared to a baseline scenario where R remains unchanged by the easing of lockdown.

Findings

The model inferred an R of 0.752 on the 13th May when England first started easing lockdown. In the most conservative scenario where R increases to 0.80 as lockdown was eased further on 1st June and then remained constant, the model predicts an excess 257 (95% 108-492) deaths and 26,447 (95% CI 11,105-50,549) cumulative cases over 90 days. In the scenario with maximal increases in R (but staying ≤1) with successive easing of lockdown, the model predicts 3,174 (95% 1,334-6,060) excess cumulative deaths and 421,310 (95% 177,012-804,811) excess cases.

Results

When levels of transmission are high, even small changes in R with easing of lockdown can have significant impacts on expected cases and deaths, even if R remains ≤1. This will have a major impact on population health, tracing systems and health care services in England.. Following an elimination strategy rather than one of maintenance of R below 1 would substantially mitigate the impact of the COVID-19 epidemic within England. This study provides urgently needed information for developing public health policy for the next stages of the pandemic.
Tracking the contribution of inductive bias to individualized internal models
Authors: Török Balázs , Nagy Dávid G. , Kiss Mariann M. , Janacsek Karolina , Németh Dezső , Orbán Gergő
Published: June 2020

Internal models capture the regularities of the environment and are central to understanding how humans adapt to environmental statistics. In general, the correct internal model is unknown to observers, instead approximate and transient ones are recruited. However, experimenters assume an ideal observer model, which captures stimulus structure but ignores the diverging hypotheses that humans form during learning. We combine non-parametric Bayesian methods and probabilistic programming to infer rich and dynamic individualised internal models from response times in an implicit visuomotor sequence learning task. We identify two contributors to the internal model: the ideal observer model and a Markov model capturing only immediate temporal dependencies between observations. Individual learning curves revealed internal models initially dominated by the Markov model, which was later traded-off with the ideal observer model. Thus, our results reveal a structured inductive bias that varies across individuals both in strength and persistence but is consistent in overall structure.
Docking studies in targeting proteins involved in cardiovascular disorders using phytocompounds fromTerminalia arjuna
Authors: Kumar Vikas , Sharma Nitin , Sourirajan Anuradha , Khosla Prem Kumar , Dev Kamal
Published: June 2020

Terminalia arjuna(Roxb.) Wight and Arnot (T. arjuna) commonly known as Arjuna has been known for its cardiotonic nature in heart failure, ischemic, cardiomyopathy, atherosclerosis, myocardium necrosis and also has been used in the treatment of different human disorders such as blood diseases, anaemia and viral diseases. Our focus has been on phytochemicals which do not exhibit any cytotoxicity and have significant cardioprotective activity. Since Protein-Ligand interactions play a key role in structure-based drug design, therefore with the help of molecular docking, we screened 19 phytochemicals present inT. arjunaand investigated their binding affinity against different cardiovascular target proteins. The three-dimensional (3D) structure of target cardiovascular proteins were retrieved from Protein Data Bank, and docked with 3D Pubchem structures of 19 phytochemicals using Autodock vina. Molecular docking and drug-likeness studies were made using ADMET properties while Lipinski’s rule of five was performed for the phytochemicals to evaluate their cardio protective activity. Among all selected phytocompounds, arjunic acid, arjungenin, and terminic acid were found to fulfill all ADMET rules, drug likeness, and are less toxic in nature. Our studies, therefore revealed that these three phytochemicals fromT. arjunacan be used as promising candidates for developing broad spectrum drugs against cardiovascular diseases.
PP1 promotes cyclin B destruction and the metaphase-anaphase transition by dephosphorylating CDC20
Authors: Bancroft James , Holder James , Geraghty Zoë , Alfonso-Pérez Tatiana , Murphy Daniel , Barr Francis A. , Gruneberg Ulrike
Published: June 2020

Ubiquitin-dependent proteolysis of cyclin B and securin initiates sister chromatid segregation and anaphase. The anaphase promoting complex/cyclosome (APC/C) and its co-activator CDC20 form the main ubiquitin E3 ligase for these proteins. APC/CCDC20is regulated by CDK1-cyclin B and counteracting PP1 and PP2A family phosphatases through modulation of both activating and inhibitory phosphorylations. Here we report that PP1 promotes cyclin B destruction at the onset of anaphase by removing specific inhibitory phosphorylation in the N-terminus of CDC20. Depletion or chemical inhibition of PP1 stabilises cyclin B and results in a pronounced delay at the metaphase-to-anaphase transition after chromosome alignment. This requirement for PP1 is lost in cells expressing CDK1-phosphorylation defective CDC206Amutants. These CDC206Acells show a normal spindle checkpoint response, but once all chromosomes have aligned rapidly degrade cyclin B and enter into anaphase in the absence of PP1 activity. PP1 therefore facilitates the metaphase-to-anaphase by promoting APC/CCDC20-dependent destruction of cyclin B in human cells.
Tumor to normal single cell mRNA comparisons reveal a pan-neuroblastoma cancer cell
Authors: Kildisiute Gerda , Kholosy Waleed M. , Young Matthew D. , Roberts Kenny , Elmentaite Rasa , van Hooff Sander R. , Khabirova Eleonora , Piapi Alice , Thevanesan Christine , Blanco Eva Bugallo , Burke Christina , Mamanova Lira , Lijnzaad Philip , Margaritis Thanasis , Holstege Frank C.P. , Tas Michelle L. , Wijnen Marc H.W.A. , van Noesel Max M. , del Valle Ignacio , Barone Giuseppe , van der Linden Reinier , Duncan Catriona , Anderson John , Achermann John C. , Haniffa Muzlifah , Teichmann Sarah A. , Rampling Dyanne , Sebire Neil J. , He Xiaoling , de Krijger Ronald R. , Barker Roger A. , Meyer Kerstin B. , Bayraktar Omer , Straathof Karin , Molenaar Jan J. , Behjati Sam
Published: June 2020

Neuroblastoma is an embryonal childhood cancer that arises from aberrant development of the neural crest, mostly within the fetal adrenal medulla. It is not established what developmental processes neuroblastoma cancer cells represent. Here, we sought to reveal the phenotype of neuroblastoma cancer cells by comparing cancer (n=16,591) with fetal adrenal single cell transcriptomes (n=57,972). Our principal finding was that the neuroblastoma cancer cell resembled fetal sympathoblasts, but no other fetal adrenal cell type. The sympathoblastic state was a universal feature of neuroblastoma cells, transcending cell cluster diversity, individual patients and clinical phenotypes. We substantiated our findings in 652 neuroblastoma bulk transcriptomes and by integrating canonical features of the neuroblastoma genome with transcriptional signals. Overall, our observations indicate that there exists a pan-neuroblastoma cancer cell state which may be an attractive target for novel therapeutic avenues.
Comparison of real-time quantitative Polymerase Chain Reaction (PCR) and digital droplet PCR for quantification of hormone membrane receptorFSHR, GPERandLHCGRtranscripts in human primary granulosa lutein cells
Authors: Sperduti Samantha , Anzivino Claudia , Villani Maria Teresa , De Feo Gaetano , Simoni Manuela , Casarini Livio
Published: June 2020

Background

Quantitative real time polymerase chain reaction (qPCR) and droplet digital PCR (ddPCR) are methods used for gene expression analysis in several contexts, including reproductive endocrinology.

Objectives

Herein, we compared qPCR and ddPCR technologies for gene expression analysis of hormone membrane receptor-encoding genes, such as follicle-stimulating hormone (FSHR), G protein-coupled estrogen (GPER)and choriogonadotropin receptors (LHCGR), as well as the commonly usedRPS7housekeeping gene, in order to identify the most reliable method to be applied for gene expression analysis in the context of human reproduction.

Methods

Total RNA was extracted from human primary granulosa cells of donor patients undergoing assisted reproduction and used for gene expression analysis by qPCR and ddPCR, after finding the optimal annealing temperature.

Results

Both techniques provided results reflecting the low number ofFSHRandGPERtranscripts, although ddPCR detected also unspecific transcripts in usingRPS7primers and quantified the low-expressed genes with major accuracy, thanks to its higher reaction efficiency. The absoluteFSHRandGPERtranscript number was also determined by ddPCR, resulting in 50- to 170-fold lower amount thanLHCGRtranscripts.

Conclusion

These results suggest that ddPCR is the candidate technology for analysis of genes with relatively low expression levels and provides useful insights for characterizing hormone receptor expression levels in the context of reproductive endocrinology.
Fusion Speed of Biomolecular Condensates
Authors: Ghosh Archishman , Zhou Huan-Xiang
Published: June 2020

Biomolecular condensates formed through phase separation have a tendency to fuse. The speed with which fusion occurs is a direct indicator of condensate liquidity, which is key to both cellular functions and diseases. Using a dual-trap optical tweezers setup, we found the fusion speeds of four types of condensates to differ by two orders of magnitude. The order of fusion speed correlates with the fluorescence of Thioflavin T, which in turn reflects the macromolecular packing density inside condensates. Unstructured protein or polymer chains pack loosely and readily rearrange, leading to fast fusion. In contrast, structured protein domains pack more closely and have to break extensive contacts before rearrangement, corresponding to slower fusion. This molecular interpretation for disparate fusion speeds portends a unified understanding of the underlying physicochemical determinants.

Entry for the Table of Contents

The tendency of biomolecular condensates to fuse is key to cellular function and diseases. Using optical tweezers, fluorescence microscopy, and theoretical modeling, Ghosh and Zhou have begun to unravel the molecular origin for disparate fusion speeds among different biomolecular condensates. They found that fusion speed is dictated by macromolecular packing density inside condensates, which can be reported by ThT fluorescence.
Phase response analyses support a relaxation oscillator model of locomotor rhythm generation inCaenorhabditis elegans
Authors: Ji Hongfei , Fouad Anthony D. , Teng Shelly , Liu Alice , Alvarez-Illera Pilar , Yao Bowen , Li Zihao , Fang-Yen Christopher
Published: June 2020

Neural circuits coordinate with muscles and sensory feedback to generate motor behaviors appropriate to an animal’s environment. InC. elegans, the mechanisms by which the motor circuit generates undulations and modulates them based on the environment are largely unclear. We quantitatively analyzedC. eleganslocomotion during free movement and during transient optogenetic muscle inhibition. Undulatory movements were highly asymmetrical with respect to the duration of bending and unbending during each cycle. Phase response curves induced by brief optogenetic inhibition of head muscles showed gradual increases and rapid decreases as a function of phase at which the perturbation was applied. A relaxation oscillator model based on proprioceptive thresholds that switch the active muscle moment was developed and is shown to quantitatively agree with data from free movement, phase responses, and previous results for gait adaptation to mechanical loadings. Our results suggest a neuromuscular mechanism underlyingC. elegansmotor pattern generation within a compact circuit.
Puromycin reactivity does not accurately localize translation at the subcellular level
Authors: Enam Syed Usman , Zinshteyn Boris , Goldman Daniel H. , Cassani Madeline , Livingston Nathan M. , Seydoux Geraldine , Green Rachel
Published: June 2020

Puromycin is a tyrosyl-tRNA mimic that blocks translation by labeling and releasing elongating polypeptide chains from translating ribosomes. Puromycin has been used in molecular biology research for decades as a translation inhibitor. The development of puromycin antibodies and derivatized puromycin analogs has enabled the quantification of active translation in bulk and single-cell assays. More recently,in vivopuromycylation assays have become popular tools for localizing translating ribosomes in cells. These assays often use elongation inhibitors to purportedly inhibit the release of puromycin-labeled nascent peptides from ribosomes. Here, usingin vitroandin vivoexperiments, we demonstrate that, even in the presence of elongation inhibitors, puromycylated peptides are released and diffuse away from ribosomes. Puromycylation assays reveal subcellular sites, such as nuclei, where puromycylated peptides accumulate post-release and which do not necessarily coincide with sites of active translation. Our findings urge caution when interpreting puromycylation assays in thein vivocontext.
It’s all relative: population estimates enhance kin recognition in the guppy
Authors: Daniel Mitchel J.
Published: June 2020

Kin recognition plays a fundamental role in social evolution, enabling active inbreeding avoidance, nepotism, and promoting cooperative social organization. Many organisms recognize kin based on phenotypic similarity – a process called phenotype matching – by comparing information associated with their own phenotype against the phenotypes of conspecifics. However, recent theory demonstrates that to accurately judge phenotypic similarity (and hence, relatedness), individuals require estimates of the population’s distribution of phenotypes as a “frame of reference.” Here, I use the Trinidadian guppy (Poecilia reticulata) to provide the first empirical test of this population estimation theory. I varied the phenotypic distributions of the groups in which focal individuals developed and found that, as adults, their patterns of inbreeding avoidance and nepotistic intrasexual competition differed as predicted by population estimation theory. Individuals reared with conspecifics more similar to themselves treated novel conspecifics as less closely related, suggesting a shifted population estimate. Individuals reared with more phenotypically variable conspecifics exhibited less extreme kin discrimination, suggesting a broader population estimate. These results provide experimental evidence that population estimates inform phenotype matching, and are acquired plastically through social experience. By calibrating phenotype matching to the population distribution of phenotypes, population estimation enhances kin recognition, increasing opportunities for the evolution of inbreeding avoidance and nepotism.
Nanopore sequencing from liquid biopsy: analysis of copy number variations from cell-free DNA of lung cancer patients
Authors: Martignano Filippo , Crucitta Stefania , Mingrino Alessandra , Semeraro Roberto , Del Re Marzia , Petrini Iacopo , Magi Alberto , Conticello Silvestro G.
Published: June 2020

Alterations in the genetic content, such as Copy Number Variations (CNVs) is one of the hallmarks of cancer and their detection is used to recognize tumoral DNA. Analysis of cell-free DNA from plasma is a powerful tool for non-invasive disease monitoring in cancer patients. Here we exploit third generation sequencing (Nanopore) to obtain a CNVs profile of tumoral DNA from plasma, where cancer-related chromosomal alterations are readily identifiable.

Compared to Illumina sequencing -the only available alternative- Nanopore sequencing represents a viable approach to characterize the molecular phenotype, both for its ease of use, costs and rapid turnaround (6 hours).
Synergistic effects of conductivity and cell-imprinted topography of chitosan-polyaniline based scaffolds for neural differentiation of adipose-derived stem cells
Authors: Eftekhari Behnaz Sadat , Eskandari Mahnaz , Janmey Paul , Samadikuchaksaraei Ali , Gholipurmalekabadi Mazaher
Published: June 2020

Smart nano-environments that mimic the stem cell niche can guide cell behavior to support functional repair and regeneration of tissues. The specific microenvironment of nervous tissue is composed of several physical signaling factors, including proper topography, flexibility, and electric conductance. In this study, a cell-imprinting technique was used to obtain a hierarchical topographical conductive scaffold based on chitosan-polyaniline (PANI) hydrogels for directing the neural differentiation of rat adipose-derived stem cells (rADSCs). A chitosan-polyaniline hydrogel was synthesized, followed by characterization tests, such as Fourier transform infrared spectroscopy (FTIR), electrical conductivity, Young modulus, and contact angle measurements. A chitosan-PANI scaffold with a biomimetic topography was fabricated by molding it on a chemically fixed culture of PC12 cells. This substrate was used to test the hypothesis that the PC12 cell-imprinted chitosan-PANI hydrogel provides the required hierarchical topographical surface to induce neural differentiation. To test the importance of spatial imprinting, rADSCs were seeded on these conductive patterned substrates, and the resulting cultures were compared to those of the same cells grown on flat conductive chitosan-polyaniline, and flat pure chitosan substrates for evaluation of adhesion, cell viability, and expression of neural differentiation markers. The morphology of rADSCs grown on conductive patterned scaffolds noticeably was significantly different from that of stem cells cultivated on flat scaffolds. This difference suggests that the change in cell and nuclear shape imposed by the patterned conductive substrate leads to altered gene expression and neural differentiation of cultured cells. In summary, a conductive chitosan-polyaniline scaffold with biomimetic topography demonstrates a promising method for enhancing the neural differentiation of rADSCs for the treatment of neurodegenerative diseases.