bluuebunny/crossref_metadata_2025 huggingface dataset:
The Public Health Gains Had Cigarette Companies Chosen to Sell Very Low Nicotine Cigarettes
Authors: Levy David T , Cummings K Michael , Heckman Bryan W , Li Yameng , Yuan Zhe , Smith Tracy T , Meza Rafael
Published: July 2020

Introduction

The U.S. Food and Drug Administration (FDA) has proposed lowering the nicotine content of cigarettes to a minimally addictive level to increase smoking cessation and reduce initiation. This study has two aims: (1) to determine when cigarette manufacturers had the technical capability to reduce cigarette nicotine content and (2) to estimate the lost public health benefits of implementing a standard in 1965, 1975, or 1985.

Methods

To determine the technical capability of cigarette companies, we reviewed public patents and internal cigarette company business records using the Truth Tobacco Industry Documents. To evaluate the impact of a very low nicotine content cigarette (VLNC) standard on smoking attributable deaths (SADs) and life-years lost (LYLs), we applied a validated (CISNET) model that uses past smoking data, along with estimates of the potential impact of VLNCs derived from expert elicitation.

Results

Cigarette manufacturers recognized that cigarettes were deadly and addictive before 1964. Manufacturers have had the technical capability to lower cigarette nicotine content for decades. Our model projected that a standard implemented in 1965 could have averted 21 million SADs (54% reduction) and 272 million LYLs (64% reduction) from 1965 to 2064, a standard implemented in 1975 could have averted 18.9 million SADs and 245.4 million LYLs from 1975 to 2074, and a standard implemented in 1985 could have averted 16.3 million SADs and 211.5 million LYLs from 1985 to 2084.

Conclusions

Millions of premature deaths could have been averted if companies had only sold VLNCs decades ago. FDA should act immediately to implement a VLNC standard.

Implications

Prior research has shown that a mandated reduction in the nicotine content of cigarettes could reduce the prevalence of smoking and improve public health. Here we report that cigarette manufacturers have had the ability to voluntarily implement such a standard for decades. We use a well-validated model to demonstrate that millions of smoking attributable deaths and life-years lost would have been averted if the industry had implemented such a standard.
Whole Genome Sequencing of Peruvian Klebsiella pneumoniae Identifies Novel Plasmid Vectors Bearing Carbapenem Resistance Gene NDM-1
Authors: Roach David , Waalkes Adam , Abanto Jorge , Zunt Joseph , Cucho Carolina , Soria Jaime , Salipante Stephen J
Published: July 2020

Background

Klebsiella pneumoniae is a bacterial pathogen with increasing rates of resistance to carbapenem antibiotics, but the population structure and genetic drivers of carbapenem-resistant K pneumoniae (CRKP) remain underexplored in developing countries. Carbapenem-resistant K pneumoniae were recently introduced into Peru but have grown rapidly in prevalence, enabling study of this pathogen as it expands into an unaffected environment.

Methods

In this study, using whole genome sequencing, we show that 3 distinct lineages encompass almost all CRKP identified in the hospital where it was first reported in Peru.

Results

The most prevalent lineage, ST348, has not been described outside of Europe, raising concern for global dissemination. We identified metallo- β -lactamase NDM-1 as the primary carbapenem resistance effector, which was harbored on a novel vector resulting from recombination between 2 different plasmids, pKP1-NDM-1 and pMS7884A.

Conclusions

This study is the first of its kind performed in Peru, and it furthers our understanding of the landscape of CRKP infections in Latin America.
Influenza With and Without Fever: Clinical Predictors and Impact on Outcomes in Patients Requiring Hospitalization
Authors: Smith Benjamin J , Price David J , Johnson Douglas , Garbutt Bruce , Thompson Michelle , Irving Louis B , Putland Mark , Tong Steven Y C
Published: July 2020

Background

The Infectious Diseases Society of America influenza guidelines no longer require fever as part of their influenza case definition in patients requiring hospitalization. However, the impact of fever or lack of fever on clinical decision-making and patient outcomes has not been studied.

Methods

We conducted a retrospective review of adult patients admitted to our tertiary health service between April 2016 and June 2019 with laboratory-confirmed influenza, with and without fever (≥37.8ºC). Patient demographics, presenting features, and outcomes were analyzed using Pearson’s chi-square test, the Wilcoxon rank-sum test, and logistic regression.

Results

Of 578 influenza inpatients, 219 (37.9%) had no fever at presentation. Fever was less likely in individuals with a nonrespiratory syndrome (adjusted odds ratio [aOR], 0.44; 95% CI, 0.26–0.77), symptoms for ≥3 days (aOR, 0.53; 95% CI, 0.36–0.78), influenza B infection (aOR, 0.45; 95% CI, 0.29–0.70), chronic lung disease (aOR, 0.55; 95% CI, 0.37–0.81), age ≥65 (aOR, 0.36; 95% CI, 0.23–0.54), and female sex (aOR, 0.69; 95% CI, 0.48–0.99). Patients without fever had lower rates of testing for influenza in the emergency department (64.8% vs 77.2%; P = .002) and longer inpatient stays (median, 2.4 vs 1.9 days; P = .015). These patients were less likely to receive antiviral treatment (55.7% vs 65.6%; P = .024) and more likely die in the hospital (3.2% vs 0.6%; P = .031), and these differences persisted after adjustment for potential confounders.

Conclusions

Absence of fever in influenza is associated with delayed diagnosis, longer length of stay, and higher mortality.
Changing the Use of HIV Pre-exposure Prophylaxis Among Men Who Have Sex With Men During the COVID-19 Pandemic in Melbourne, Australia
Authors: Chow Eric P F , Hocking Jane S , Ong Jason J , Schmidt Tina , Buchanan Andrew , Rodriguez Elena , Maddaford Kate , Patel Prital , Fairley Christopher K
Published: July 2020

We surveyed 204 men who have sex with men (MSM) who were pre-exposure prophylaxis (PrEP) users. One in 4 daily PrEP users stopped taking PrEP during the COVID-19 pandemic, and 5% switched to on-demand PrEP. Most men reduced PrEP use because they stopped having casual sex and reduced the number of casual partners during the COVID-19 pandemic.
Minimizing Time to Optimal Antimicrobial Therapy for Enterobacteriaceae Bloodstream Infections: A Retrospective, Hypothetical Application of Predictive Scoring Tools vs Rapid Diagnostics Tests
Authors: Cwengros Laura N , Mynatt Ryan P , Timbrook Tristan T , Mitchell Robert , Salimnia Hossein , Lephart Paul , Pogue Jason M
Published: July 2020

Background

Bloodstream infections (BSIs) due to ceftriaxone (CRO)-resistant Enterobacteriaceae are associated with delays in time to appropriate therapy and worse outcomes compared with infections due to susceptible isolates. However, treating all at-risk patients with empiric carbapenem therapy risks overexposure. Strategies are needed to appropriately balance these competing interests. The purpose of this study was to compare 4 methods for achieving this balance.

Methods

This was a retrospective hypothetical observational study of patients at the Detroit Medical Center with monomicrobial BSIs due to E. coli, K. oxytoca, K. pneumoniae, or P. mirabilis. This study compared the effectiveness of 4 methods to predict CRO resistance at the time of organism isolation. Three methods were based on applying published extended-spectrum beta-lactamase (ESBL) scoring tools. The fourth method was based on the presence or absence of the CTX-M marker from Verigene.

Results

Four hundred fifty-one Enterobacteriaceae BSIs were included, 73 (16%) of which were CRO-resistant. Verigene accurately predicted ceftriaxone susceptibility for 97% of isolates, compared with 70%–81% using the scoring tools (P < .001). Verigene was associated with fewer cases of treatment with CRO when the isolate was CRO-resistant (15% vs 63%–71% with scoring tools) and fewer cases of overtreatment with a carbapenem for CRO-susceptible strains (0.3% vs 10%–12%).

Conclusions

Verigene significantly outperformed published ESBL scoring tools for identifying CRO-resistant Enterobacteriaceae BSI. Institutions should validate scoring tools before implementation. Stewardship programs should consider adoption of rapid diagnostic tests to optimize early therapy.
Minimally Invasive Scoliosis Correction in Parkinson Disease: Retrospective Case Series
Authors: Nunna Ravi S , Fessler Richard G
Published: July 2020

BACKGROUND

Parkinson disease (PD) is the second most common neurodegenerative disease in the United States. In the context of the disability inherent to PD, the additional physical challenges and pain from scoliosis can be debilitating for these patients. However, the magnitude of surgery required to correct the deformity combined with the medical co-morbidities and frailty in this population of patients makes surgery very risky.

OBJECTIVE

To investigate clinical presentations and outcomes of patients with PD that underwent minimally invasive long-segment fusion for scoliosis correction.

METHODS

A retrospective chart review was performed over the years 2007 to 2017 for patients diagnosed with PD undergoing long-segment spinal fusion (5 or more levels) with the use of circumferential minimally invasive spine surgery techniques. Data including age, sex, race, medical co-morbidities, presenting symptoms, radiographic findings, surgical procedure, case history, and complications were collected from the medical record.

RESULTS

Retrospective chart review revealed three patients that met the inclusion criteria. They included 2 males and 1 female, with a mean age of 68.7 yr (range 63-75 yr). Ability to maintain upright posture, return to activities of daily living, and visual analog scale (VAS)-back improved in all patients at 1-yr follow-up. Results were durable at 2-yr follow-up. No medical complications were observed.

CONCLUSION

The generally positive results suggest that minimally invasive technique could have significant benefits in this high-risk group of patients.
Dengue epidemic in Malaysia: urban versus rural comparison of dengue immunoglobulin G seroprevalence among Malaysian adults aged 35–74 years
Authors: Azami Nor Azila Muhammad , Moi Meng Ling , Salleh Sharifah Azura , Neoh Hui-min , Kamaruddin Mohd Arman , Jalal Nazihah Abdul , Ismail Norliza , Takasaki Tomohiko , Kurane Ichiro , Jamal Rahman
Published: July 2020

Background

A periodic serosurvey of dengue seroprevalence is vital to determine the prevalence of dengue in countries where this disease is endemic. This study aimed to determine the prevalence of dengue immunoglobulin G (IgG) seropositivity among healthy Malaysian adults living in urban and rural areas.

Methods

A total of 2598 serum samples (1417 urban samples, 1181 rural samples) were randomly collected from adults ages 35–74 y. The presence of the dengue IgG antibody and neutralising antibodies to dengue virus (DENV) 1–4 was determined using enzyme-linked immunosorbent assay and the plaque reduction neutralisation test assay, respectively.

Results

The prevalence of dengue IgG seropositivity was 85.39% in urban areas and 83.48% in rural areas. The seropositivity increased with every 10-y increase in age. Ethnicity was associated with dengue seropositivity in urban areas but not in rural areas. The factors associated with dengue seropositivity were sex and working outdoors. In dengue IgG-positive serum samples, 98.39% of the samples had neutralising antibodies against DENV3, but only 70.97% of them had neutralising antibodies against DENV4.

Conclusion

The high seroprevalence of dengue found in urban and rural areas suggests that both urban and rural communities are vital for establishing and sustaining DENV transmission in Malaysia.
Histopathological Spectrum and Immunophenotypic Characterization of Symmetrical Drug-Related Intertriginous and Flexural Exanthema
Authors: Muresan Ana-Maria , Metze Dieter , Böer-Auer Almut , Braun Stephan A.
Published: July 2020

Introduction:

Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) is a clinically very well-defined drug eruption, but the histopathological findings are still considered to be nonspecific.

Objectives:

To characterize the histopathological and immunophenotypical features of SDRIFE.

Material and Methods:

We performed a retrospective study that identified 11 biopsies from 9 patients with SDRIFE. The histopathological features were analyzed in conjunction with the immunohistochemical findings.

Results:

The most common histopathological feature was basal cell vacuolization, which was often associated with necrotic keratinocytes and focal spongiosis. TIA1+T cells and neutrophils were frequently detected in the epidermis and at the dermoepidermal junction. The dermal inflammatory infiltrate was mixed, consisting of CD3+T cells, macrophages, granulocytes, low numbers of CD20+B cells, and plasma cells. A combination of histopathological patterns was observed in 5 cases. The most frequent combined histopathological patterns were interface dermatitis, spongiotic dermatitis, and psoriasiform dermatitis. Other histopathological patterns found in different combinations were pustular dermatitis, perivascular and interstitial neutrophilic dermatitis, and interstitial granulomatous dermatitis. In the other 4 cases, a single histopathological pattern predominated, such as psoriasiform dermatitis, vacuolar interface dermatitis of erythema multiforme-like type, or superficial and deep perivascular and interstitial dermatitis with eosinophils and neutrophils.

Conclusions:

SDRIFE is characterized histologically by a vacuolar interface dermatitis induced by cytotoxic T lymphocytes and neutrophilic granulocytes. This pattern may be obscured by accompanying spongiotic, psoriasiform, or pustular features combined with a mixed superficial and sometimes deep dermal infiltrate.
Lacrimal Sac Actinomycosis: A Masquerade of Lacrimal Sac Malignancy
Authors: Singh Manpreet , Saikia Uma Nahar , Kaur Manpreet , Sharma Manjula , Gupta Pankaj
Published: July 2020

A 60-year-old woman had blood-stained discharge with intermittent hemolacria from the left eye, of 3 months duration. The ophthalmic examination showed a firm, nontender, and immobile mass in the left lacrimal sac region. The sac regurgitation test was positive with purulent blood-stained discharge. Lacrimal punctum and canaliculi of both sides were normal. CT scan of orbits showed a hyperdense lesion in the left lacrimal sac region without bone erosion. A complete dacryocystectomy was performed, and the histopathology revealed actinomycosis of the lacrimal sac. At 14 months of follow-up visit, the patient has no clinical evidence of recurrence.
Recurrence of a Totally Excised Cavernous Venous Malformation 25 Years Later
Authors: Kiratli Hayyam , Koç Irem , Toprak Hilal , Yildirim Selma , Söylemezoğlu Figen
Published: July 2020

Recurrence of cavernous venous malformation is exceedingly rare. In 1995, a 16-year-old woman was referred for left axial proptosis. Her left visual acuity was 20/200, and there were choroidal folds in the OS. MRI studies showed a well-circumscribed retrobulbar intraconal mass in the left orbit. The tumor was totally removed with intact capsule through a transconjunctival orbitotomy and proved to be a cavernous venous malformation. In 2020, at the age of 41 years and 25 years after the operation, she again presented with left proptosis. Imaging results were very similar to those at first presentation. This tumor was also extirpated in its entirety via an inferior forniceal orbitotomy with the histopathologic diagnosis of a cavernous venous malformation. Her final left visual acuity remained 20/50. Women with orbital cavernous venous malformations, especially those who undergo surgical removal at a relatively young age are advised to have long-term follow up complemented with occasional imaging studies.
Patient-Specific Implants in Oculofacial Plastic Surgery
Authors: Copperman Thomas S , Idowu Oluwatobi O. , Jalaj Sanjai , Winn Bryan J. , Pham Chau , Setabutr Pete , Kersten Robert C. , Vagefi M. Reza
Published: July 2020

Purpose:

To investigate how patient-specific implants (PSIs) are being utilized for periocular facial skeletal reconstruction. Specifically, to characterize indications for custom implants, areas of reconstruction, intraoperative variables impacting implant placement, as well as to report on postoperative outcomes.

Materials and Methods:

A retrospective chart review was performed for patients who received a PSI for periocular skeletal reconstruction between 2015 and 2019. Three independent academic centers were included in this study, which encompassed 4 different primary surgeons. Medical records, radiographic imaging, and operative reports were reviewed.

Results:

Eleven patients, 8 females and 3 males, ages ranging from 15 to 63 years old received PSIs. The average duration of follow up was 16 months ± 6.6 months (range: 9–30 months). The most common underlying etiology for reconstruction was prior trauma (54.5%) followed by benign tumor resection (18.2%). The most frequent area of reconstruction involved the inferior orbital rim and adjacent maxilla (63.6%). Implant materials included porous polyethylene, polyetheretherketone, and titanium. Six implants required intraoperative modification, most commonly accommodate critical neurovascular structures (66.6%) or improve contour (33.3%). Two postoperative complications were noted, both in the form of infection with 1 implant requiring removal.

Conclusions:

Reconstruction of complex facial skeletal defects can be achieved by utilizing computer-assisted design software and 3D printing techniques to create PSIs. These implants represent the most customizable option for symmetric restoration of the facial skeleton by not only addressing structural deficits but also volumetric loss. This was particularly apparent in reconstruction of the orbital rim and midface. PSIs were found to be of most benefit in patients with prior trauma or complex skeletal defects after tumor resection.
Metabolic Syndrome in Commercial Truck Drivers
Authors: Robbins Riann B. , Thiese Matthew S. , Ott Ulrike , Wood Eric M. , Effiong Atim , Murtaugh Maureen , Kapellusch Jay , Cheng Melissa , Hegmann Kurt
Published: July 2020

Introduction:

Commercial motor vehicle drivers, such as truck drivers, experience unique health, lifestyle, and occupational challenges directly associated with their profession.

Methods:

All participants in this multistate cross-sectional study completed questionnaire measurements. Participants were categorized with metabolic syndrome (MetS) if they had at least three of the five modified criteria used in the joint scientific statement on metabolic syndrome.

Results:

Overall MetS prevalence was 52.4% (n = 428) of the 817 participants. Prevalence of MetS criteria were waist circumference (n = 634, 77.0%), low HDL cholesterol (n = 580, 71.0%), elevated triglycerides (n = 552, 67.6%), elevated blood pressure (n = 175, 21.2%), and elevated hemoglobin A1c (n = 97, 11.9%). Truck drivers were 2.7 times more likely to have MetS compared to the general working population.

Conclusion:

Truck drivers in the United States have a high prevalence of MetS compared to the general working population.
Tuberculosis Screening, Testing, and Treatment of US Health Care Personnel
Authors: Thanassi Wendy , Behrman Amy J. , Reves Randall , Russi Mark , Swift Melanie , Warkentin Jon , Miyakawa Ryo , Wegener Donna , Budnick Lawrence , Murray Ellen , Scarpita Ann , Hurst Bobbi Jo , Foster-Chang Sarah , Mathew Trini , Gruden MaryAnn , Higashi Julie , Hudson Thomas Warner
Published: July 2020

On May 17, 2019, the US Centers for Disease Control and Prevention and National Tuberculosis Controllers Association issued new Recommendations for Tuberculosis Screening, Testing, and Treatment of Health Care Personnel, United States, 2019, updating the health care personnel-related sections of the Guidelines for Preventing the Transmission of Mycobacterium tuberculosis in Health-Care Settings, 2005. This companion document offers the collective effort and experience of occupational health, infectious disease, and public health experts from major academic and public health institutions across the United States and expands on each section of the 2019 recommendations to provide clarifications, explanations, and considerations that go beyond the 2019 recommendations to answer questions that may arise and to offer strategies for implementation.
The new place of enterohormones in intestinal failure
Authors: Daoud Dane Christina , Joly Francisca
Published: July 2020

Purpose of review

Since the approval of teduglutide, a glucagon-like peptide-2 (GLP-2) analog, for the treatment of patients with short bowel syndrome (SBS) associated with intestinal failure, enterohormone therapy has received significant interest and is becoming the first choice of treatment in selected patients. As such, it is paramount to assess and understand the new place of hormonal therapy in the algorithm of treatments in SBS-intestinal failure.

Recent findings

Specialized intestinal failure units have recently reported their outcomes with teduglutide to evaluate if they are consistent with the phase III trials results. SBS-intestinal failure patients are very heterogenous including their response to this treatment, hence the importance of real-life studies beyond the context of clinical trials. Moreover, it is essential to find a consensus on criteria identifying candidate patients for teduglutide. In addition, the impact of teduglutide on quality of life and its cost-effectiveness are emerging as well as new enterohormone treatments are being studied whether it is long action GLP-2 analog or other ileocolonic break hormones like glucagon-like peptide-1 analog.

Hormonotherapy is currently modifying the natural history of patients with SBS-intestinal failure by decreasing their need for parenteral support and possibly even complications associated with long-term parenteral support. Enterohormone treatment is now the cornerstone in SBS-intestinal failure and should be offered as a first-line therapy to selected patients.
Experience of Ambulatory Cancer Care
Authors: Vehviläinen-Julkunen Katri , Turpeinen Saija , Kvist Tarja , Ryden-Kortelainen Margaretha , Nelimarkka Siiri , Enshaeifar Shirin , Faithfull Sara ,   for INEXCA Consortium
Published: July 2020

Background

The move of cancer treatment into the outpatient setting can impact patient experience. Understanding how service delivery change impacts different people requires service feedback to inform future delivery development. The use of patient experience questionnaires often generates large amount of free-text data that are difficult to analyze.

Objective

The aim of this study was to describe a proof-of-concept study exploring the experiences and perceptions of people undergoing cancer treatment, using novel analysis techniques to provide rapid free-text data analysis.

Method

This was a mixed-methods qualitative analysis from qualitative questions gathered in Finland using the National Cancer Patient Experience Survey (n = 92 of 208 patients) and supplemented with 7 focus groups (31 people with cancer). Data were analyzed using natural language processing, via an automated sentiment analysis algorithm and supported with focus groups to inform the initial thematic analysis.

Results

Participants were on average 65 years of age. Of the 196 free-text comments, 121 (73.6%) were positive about patient experiences and 75 (38.5%) negative with suggestions for improvement.

Conclusion

Communication between patients and clinicians was an indicator of quality, and lack of psychological support was a barrier to quality care provision. The methodology of using sentiment analysis for free content to review quality was demonstrated through this study as a novel and feasible method to look at large-scale qualitative data.

Implications for Practice

Using the free content on experience of care questionnaire to review gaps or needs in services is valuable in developing future practice.
Cardiopulmonary Bypass Duration and the Incidence of Pressure Injuries in Patients Undergoing Cardiovascular Surgery
Authors: Chen Xiaomei , Liao Haitao , Gao Wen , Chen Yunchao , Huang Jiegang , Wei Yiping
Published: July 2020

PURPOSE:

The purpose of our study was to investigate the association between cardiopulmonary bypass (CPB) duration and the incidence of pressure injuries (PIs) in patients undergoing cardiovascular surgery.

DESIGN:

Retrospective chart review.

SUBJECTS AND SETTING:

Two hundred and eighty-eight patients who underwent cardiovascular surgery with CPB from January 2016 through December 2016 in a 2000-bed general hospital, which integrates medical service, education, and research and in which 300 to 350 cardiovascular surgical procedures with CPB are performed each year.

METHODS:

We retrospectively collected data from patients' medical records. Univariate analysis and multivariate logistic regression analysis were performed to identify the independent risk factors for the development of PI. In addition, a simple linear regression model was conducted to assess the relationship between CPB duration and PI development.

RESULTS:

Of the 288 patients, 56 developed 80 PIs, with an incidence of 19.4% (95% confidence interval, 14.9%-24.3%). Multivariate logistic regression analysis showed that CPB duration, use of vasoactive drugs, and diabetes mellitus were independent risk factors for the development of PIs in patients receiving cardiovascular surgery. Median CPB duration was significantly longer in the group with PIs compared with the group without PIs (144 [range 48-415] minutes compared with 102.5 [range 16-678] minutes, P = .000). This result was consistent in the subgroup analysis of pediatric and adult patients. Pressure injuries also increased proportionally with CPB duration, from 12.2% at 60 minutes or shorter to 45.5% at more than 300 minutes (P = .002, R
2 = 0.936).

CONCLUSIONS:

The CPB duration, use of vasoactive drugs, and presence of diabetes mellitus are independent risk factors for the development of PIs in patients undergoing cardiovascular surgery with CPB. Our findings indicated that PI incidence increased incrementally with the duration of CPB. We recommend implementing measures to prevent PIs in cardiovascular surgical patients, especially those undergoing prolonged CPB, receiving vasoactive drugs, and diagnosed with diabetes.
Foot Health Assessment and Problem Identification in a Dominican Batey Community
Authors: O'Connor Jennifer J. , Enriquez Maithe , Wipke-Tevis Deidre D.
Published: July 2020

PURPOSE:

Foot problems can adversely impact foot function and quality of life. Foot problems are often overlooked, particularly in populations with limited health care access. Little is known about the foot health of Haitian immigrants who live and work in the bateyes (rural sugarcane villages) of the Dominican Republic. These immigrant workers may experience foot problems that could affect foot function and the ability to work and provide for their families.

DESIGN:

Cross-sectional, exploratory, descriptive study design.

SUBJECTS AND SETTING:

A convenience sample of adults was recruited from an ongoing community-based participatory research project evaluating a mobile hypertension screening and treatment clinic program in 11 Dominican batey communities.

METHODS:

Foot health was assessed using the Foot Problems Checklist, a 24-item survey instrument developed for this study based on a review of the literature and foot clinician expertise. A certified foot care nurse recorded foot health data on the Foot Problems Checklist via visual and physical inspection.

RESULTS:

Study participants were 25 females and 16 males, aged 18 to 90 years, and all had at least one foot health problem. The most common foot problems were calluses (78%), dry skin (76%), thick nails (59%), jagged nails (29%), long/overgrown nails (17%), and skin fissures (12%).

CONCLUSIONS:

While the foot problems we observed were not considered serious, they could become progressively debilitating and be prevented with proper self-management guided by appropriate knowledge and skills and available supplies. We recommend the development and testing of foot care self-management interventions deliverable via mobile clinics to increase access and improve foot health outcomes.
Creating a Pediatric and Neonatal Pressure Injury Prevention Program When Evidence Was Sparse or Absent
Authors: Nie Ann Marie
Published: July 2020

Pressure injuries are a common occurrence in the pediatric population, but only within the past decade has prevention intervention been developed specifically for the pediatric patient. At the time of the safety collaborative described, pressure injuries in children were considered nonexistent. A safety collaborative was formed to see if the pressure injury prevention guidelines for adults could be adapted to the pediatric patient. The PDSA (plan-do-study-act) quality improvement model was utilized. The collaborative brought forth not only prevention interventions specifically for the pediatric population, but the work also described medical device-related pressure injuries that were not being considered prior to the collaborative. Several national initiatives transpired that elevated pressure injury prevention of the pediatric population as a hospital safety concern.
Sequential MAVS- and MyD88/TRIF-signaling triggers anti-viral responses of tick-borne encephalitis virus-infected murine astrocytes
Authors: Ghita Luca , Breitkopf Veronika , Mulenge Felix , Pavlou Andreas , Gern Olivia Luise , Durán Verónica , Prajeeth Chittappen Kandiyil , Kohls Moritz , Jung Klaus , Stangel Martin , Steffen Imke , Kalinke Ulrich
Published: July 2020

Tick-borne encephalitis virus (TBEV), a member of theFlaviviridaefamily, is typically transmitted upon tick bite and can cause meningitis and encephalitis in humans. In TBEV infected mice,mitochondrial antiviral signaling protein(MAVS), the downstream adaptor ofretinoic acid inducible gene I-like receptor(RLR)-signaling, is needed to induce early type I interferon (IFN) responses and to confer protection. To identify the brain resident cell subset that produces protective IFN-β in TBEV infected mice, we isolated neurons, astrocytes and microglia and exposed these cells to TBEVin vitro. Under such conditions, neurons showed the highest percentage of infected cells, whereas astrocytes and microglia were infected to a lesser extent. In the supernatant (SN) of infected neurons, IFN-β was not detectable, while infected astrocytes showed very high and microglia low IFN-β production. Transcriptome analyses of astrocytes implied that MAVS-signaling was needed early after TBEV infection. Accordingly, MAVS-deficient astrocytes showed enhanced TBEV infection and significantly reduced early IFN-β responses. At later time points, moderate amounts of IFN-β were detected in the SN of infected MAVS-deficient astrocytes. Transcriptome analyses indicated that MAVS-deficiency negatively affected the induction of early anti-viral responses, which resulted in significantly increased TBEV replication. Treatment with MyD88 and TRIF inhibiting peptides reduced late IFN-β responses of TBEV infected WT astrocytes and entirely blocked IFN-β responses of infected MAVS-deficient astrocytes. Thus, upon TBEV exposure of brain-resident cells, astrocytes are important IFN-β producers that show biphasic IFN-β induction that initially depends on MAVS- and later on MyD88/TRIF-signaling.
Single-cell analysis of developing B cells reveals dynamic gene expression networks that govern B cell development and transformation
Authors: Lee Robin D. , Munro Sarah A. , Knutson Todd P. , LaRue Rebecca S. , Heltemes-Harris Lynn M. , Farrar Michael A.
Published: July 2020

Integration of external signals and B-lymphoid transcription factor activities orchestrate B cell lineage commitment through alternating cycles of proliferation and differentiation, producing a diverse repertoire of mature B cells. We used single-cell transcriptomics and proteomics to characterize B cell development. Our analysis revealed unique transcriptional signatures that refine the pre-B cell expansion stages into novel pre-BCR-dependent and pre-BCR-independent proliferative phases. These changes correlate with unexpected dynamic and reciprocal changes in expression of the transcription factor EBF1 and the RNA binding protein YBX3, that are defining features of the pre-BCR-dependent stage. Using pseudotime analysis, we further characterize the expression kinetics of different biological modalities across B cell development, including transcription factors, cytokines, chemokines, and their associated receptors. Our findings reveal the underlying heterogeneity of developing B cells and point to key developmental nodes linked to B cell transformation.
Recurrent training rejuvenates and enhances transcriptome and methylome responses in young and older human muscle
Authors: Blocquiaux Sara , Ramaekers Monique , Van Thienen Ruud , Nielens Henri , Delecluse Christophe , De Bock Katrien , Thomis Martine
Published: July 2020

Background

The interaction between the muscle methylome and transcriptome is understudied during ageing and periods of resistance training in young, but especially older adults. In addition, more information is needed on the role of retained methylome training adaptations in muscle memory to understand muscle phenotypical and molecular restoration after inactivity or disuse.

Methods

We measured CpG methylation (microarray) and RNA expression (RNA sequencing) in young (n = 5; age = 22 ± 2 yrs) and older (n = 6; age = 65 ± 5 yrs) vastus lateralis muscle samples, taken at baseline, after 12 weeks of resistance training, after training interruption (2 weeks of leg immobilization in young men, 12 weeks of detraining in older men) and after 12 weeks of retraining to identify muscle memory-related adaptations and rejuvenating effects of training.

Results

We report that of the 427 differentially expressed genes with advanced age, 71 % contained differentially methylated (dm)CpGs in older versus young muscle. The more dmCpGs within a gene, the clearer the inverse methylation-expression relationship. Around 73 % of the age-related dmCpGs approached younger methylation levels when older muscle was trained for 12 weeks. A second resistance training period after training cessation increased the number of hypomethylated CpGs and upregulated genes in both young and older muscle. We found indication for an epi-memory within pro-proliferatingAMOTL1in young muscle and mechanosensing-relatedVCLin older muscle. For the first time, we integrate muscle methylome and transcriptome data in relation to both ageing and training/inactivity-induced responses and identify focal adhesion as an important pathway herein.

Conclusion

Previously trained muscle is more responsive to training than untrained muscle at methylome and transcriptome level and recurrent resistance training can partially restore ageing-induced methylome alterations.
Phylogeny inference under the general Markov model using MST-backbone
Authors: Kalaghatgi Prabhav
Published: July 2020

Motivation

Phylogeny inference via maximum likelihood is NP-hard. Current methods make simplifying assumptions such as stationarity, homogeneity, and time-reversibility for computational ease. The stationarity assumption is violated by empirical observations of GC content evolution, and might systematically bias phylogeny inference. The general Markov model (GM) is a suitable alternative to stationary models because it allows for the evolution of GC content. Related work on the GM model has predominantly focused on inferring unrooted trees using either the log-det distance or phylogenetic invariants.

Methods

We adapted the structural EM framework to perform tree search under the GM model (SEM-GM). Additionally, we implemented a minimum spanning tree framework called MST-backbone to improve the scalability of SEM-GM by constraining search through tree space. MST-backbone(SEM-GM) was used to infer unrooted trees, which are subsequently rooted under the GM model; the latter procedure is called rSEM-GM. We compared our method with RAxML-NG, IQ-TREE, and FastTree on simulated data. We validated our methods on six empirical datasets.

Results

Estimated experimental phylogenies are rooted with high accuracy under the GM model (recall ranging from 80% to 94%). However, virus phylogenies are not realistically rooted, suggesting that the GM model may be overtrained on some empirical datasets. The comparative analysis of simulated data suggests that MST-backbone(SEM-GM) and FastTree scale linearly whereas rSEM-GM, RAxML-NG, and IQ-TREE scale quadratically. The results on empirical data suggest that it is not necessary to use the general time-reversible model for computational ease.

Availability

https://github.com/prabhavk/mst-backbone-sem-gm

Contact

prabhav.kalaghatgi@molgen.mpg.de

Supplementary information

Supplementary data are available online
Bi-channel Image Registration and Deep-learning Segmentation (BIRDS) for efficient, versatile 3D mapping of mouse brain
Authors: Wang Xuechun , Zeng Weilin , Yang Xiaodan , Fang Chunyu , Han Yunyun , Fei Peng
Published: July 2020

We have developed an open-source software called BIRDS (bi-channel image registration and deep-learning segmentation) for the mapping and analysis of 3D microscopy data of mouse brain. BIRDS features a graphical user interface that is used to submit jobs, monitor their progress, and display results. It implements a full pipeline including image pre-processing, bi-channel registration, automatic annotation, creation of 3D digital frame, high-resolution visualization, and expandable quantitative analysis (via link with Imaris). The new bi-channel registration algorithm is adaptive to various types of whole brain data from different microscopy platforms and shows obviously improved registration accuracy. Also, the attraction of combing registration with neural network lies in that the registration procedure can readily provide training data for network, while the network can efficiently segment incomplete/defective brain data that are otherwise difficult for registration. Our software is thus optimized to enable either minute-timescale registration-based segmentation of cross-modality whole-brain datasets, or real-time inference-based image segmentation for various brain region of interests. Jobs can be easily implemented on Fiji plugin that can be adapted for most computing environments.
Next-generation diagnostics: virus capture facilitates a sensitive viral diagnosis for epizootic and zoonotic pathogens including SARS-CoV-2
Authors: Wylezich Claudia , Calvelage Sten , Schlottau Kore , Ziegler Ute , Pohlmann Anne , Höper Dirk , Beer Martin
Published: July 2020

Background

The detection of pathogens in clinical and environmental samples using high-throughput sequencing (HTS) is often hampered by large amounts of background information, which is especially true for viruses with small genomes. Enormous sequencing depth can be necessary to compile sufficient information for identification of a certain pathogen. Generic HTS combining with in-solution capture enrichment can markedly increase the sensitivity for virus detection in complex diagnostic samples.

Methods

A virus panel based on the principle of biotinylated RNA-baits was developed for specific capture enrichment of epizootic and zoonotic viruses (VirBaits). The VirBaits set was supplemented by a SARS-CoV-2 predesigned bait set for testing recent SARS-CoV-2 positive samples. Libraries generated from complex samples were sequenced via generic HTS and afterwards enriched with the VirBaits set. For validation, an internal proficiency test for emerging epizootic and zoonotic viruses (African swine fever virus, Ebolavirus, Marburgvirus, Nipah henipavirus, Rift Valley fever virus) was conducted.

Results

The VirBaits set consists of 177,471 RNA-baits (80-mer) based on about 18,800 complete viral genomes targeting 35 epizootic and zoonotic viruses. In all tested samples, viruses with both DNA and RNA genomes were clearly enriched ranging from about 10-fold to 10,000-fold for viruses including distantly related viruses with at least 72% overall identity to viruses represented in the bait set. Viruses showing a lower overall identity (38% and 46%) to them were not enriched but could nonetheless be detected based on capturing conserved genome regions. The internal proficiency test supports the improved virus detection using the combination of HTS plus targeted enrichment but also point to the risk of carryover between samples.

Conclusions

The VirBaits approach showed a high diagnostic performance, also for distantly related viruses. The bait set is modular and expandable according to the favored diagnostics, health sector or research question. The risk of carryover needs to be taken into consideration. The application of the RNA-baits principle turned out to be user-friendly, and even non-experts (without sophisticated bioinformatics skills) can easily use the VirBait workflow. The rapid extension of the established VirBaits set adapted to actual outbreak events is possible without any problems as shown for SARS-CoV-2.
ROX Index Predicts Intubation in Patients with COVID-19 Pneumonia and Moderate to Severe Hypoxemic Respiratory Failure Receiving High Flow Nasal Therapy
Authors: Patel Maulin , Chowdhury Junad , Mills Nicole , Marron Robert , Gangemi Andrew , Dorey-Stein Zachariah , Yousef Ibraheem , Zheng Matthew , Tragesser Lauren , Giurintano Julie , Gupta Rohit , Rali Parth , D’Alonzo Gilbert , Zhao Huaqing , Patlakh Nicole , Marchetti Nathaniel , Criner Gerard J. , Gordon Matthew ,   for the Temple University COVID-19 Research Group
Published: July 2020

Use of high flow nasal therapy (HFNT) to treat COVID-19 pneumonia has been greatly debated around the world due to concern for increased healthcare worker transmission and delays in invasive mechanical Ventilation (IMV).

Methods

A retrospective analysis of consecutive patients admitted to Temple University Hospital in Philadelphia, Pennsylvania, from March 10, 2020, to May 17, 2020 with moderate to severe respiratory failure treated with High Flow nasal therapy (HFNT). HFNT patients were divided into two groups: HFNT only and HFNT progressed to IMV. The primary outcome was the ability of the ROX index to predict the need of IMV.

Results

Of the 837 patients with COVID-19, 129 met inclusion criteria. The mean age was 60.8 (±13.6) years, BMI 32.6 (±8), 58 (45 %) were female, 72 (55.8%) were African American, 40 (31%) Hispanic. 48 (37.2%) were smokers. Mean time to intubation was 2.5 days (± 3.3). ROX index of less than 5 at HFNT initiation was predictive of progression to IMV (OR = 2.137, p = 0,052). Any decrease in ROX index after HFNT initiation was predictive of intubation (OR= 14.67, p <0.0001). ΔROX (<=0 versus >0), peak D-dimer >4000 and admission GFR < 60 ml/min were very strongly predictive of need for IMV (ROC = 0.86, p=). Mortality was 11.2% in HFNT only group versus 47.5% in the HFNT progressed to IMV group (p,0.0001). Mortality and need for pulmonary vasodilators were higher in the HNFT progressed to IMV group.

Conclusion

ROX index is a valuable, noninvasive tool to evaluate patients with moderate to severe hypoxemic respiratory failure in COVID-19 treated with HFNT. ROX helps predicts need for IMV and thus limiting morbidity and mortality associated with IMV.
Scale-free structure of cancer networks and their vulnerability to hub-directed combination therapy
Authors: Chen Andrew X. , Zopf Christopher J. , Mettetal Jerome , Shyu Wen Chyi , Bolen Joseph , Chakravarty Arijit , Palani Santhosh
Published: July 2020

Background

The effectiveness of many targeted therapies is limited by toxicity and the rise of drug resistance. A growing appreciation of the inherent redundancies of cancer signaling has led to a rise in the number of combination therapies under development, but a better understanding of the overall cancer network topology would provide a conceptual framework for choosing effective combination partners. In this work, we explore the scale-free nature of cancer protein-protein interaction networks in 14 indications. Scale-free networks, characterized by a power-law degree distribution, are known to be resilient to random attack on their nodes, yet vulnerable to directed attacks on their hubs (their most highly connected nodes).

Results

Consistent with the properties of scale-free networks, we find that lethal genes are associated with ∼5-fold higher protein connectivity partners than non-lethal genes. This provides a biological rationale for a hub-centered combination attack. Our simulations show that combinations targeting hubs can efficiently disrupt 50% of network integrity by inhibiting less than 1% of the connected proteins, whereas a random attack can require inhibition of more than 30% of the connected proteins.

Conclusions

We find that the scale-free nature of cancer networks makes them vulnerable to focused attack on their highly connected protein hubs. Thus, we propose a new strategy for designing combination therapies by targeting hubs in cancer networks that are not associated with relevant toxicity networks.
Building a tRNA thermometer to access the world’s biochemical diversity
Authors: Cimen Emre , Jensen Sarah E. , Buckler Edward S.
Published: July 2020

Because ambient temperature affects biochemical reactions, organisms living in extreme temperature conditions adapt protein composition and structure to maintain biochemical functions. While it is not feasible to experimentally determine optimal growth temperature (OGT) for every known microbial species, organisms adapted to different temperatures have measurable differences in DNA, RNA, and protein composition that allow OGT prediction from genome sequence alone. In this study, we built a model using tRNA sequence to predict OGT. We used tRNA sequences from 100 archaea and 683 bacteria species as input to train two Convolutional Neural Network models. The first pairs individual tRNA sequences from different species to predict which comes from a more thermophilic organism, with accuracy ranging from 0.538 to 0.992. The second uses the complete set of tRNAs in a species to predict optimal growth temperature, achieving a maximumr2of 0.86; comparable with other prediction accuracies in the literature despite a significant reduction in the quantity of input data. This model improves on previous OGT prediction models by providing a model with minimum input data requirements, removing laborious feature extraction and data preprocessing steps, and widening the scope of valid downstream analyses.