bluuebunny/crossref_metadata_2025 huggingface dataset:
Marijuana Use, Sexual Behaviors, and Prevalent Sexually Transmitted Infections Among Sexually Experienced Males and Females in the United States: Findings From the National Health and Nutrition Examination Surveys
Authors: Patel Eshan U. , White Jodie L. , Gaydos Charlotte A. , Quinn Thomas C. , Mehta Shruti H. , Tobian Aaron A.R.
Published: July 2020

Background

Several national guidelines consider illicit drug use as an indication for testing and/or counseling for some sexually transmitted infections (STIs). The legal and social landscape of marijuana use is changing, and its relevance with STI risk is unclear.

Methods

Sex-specific prevalence of T. vaginalis and/or C. trachomatis infection was examined by past-year marijuana use (no vs yes) among 2958 sexually experienced, 20- to 39-year-old participants of the 2013–2016 National Health and Nutrition Examination Surveys. Prevalence ratios (PRs) with 95% confidence intervals [CIs] were estimated by Poisson regression. Adjusted PRs (aPR) were estimated following propensity score covariate-adjustment accounting for sociodemographics, alcohol use, injection drug use, depression, and age at sexual debut.

Results

Past-year marijuana use was reported by 27.3% and 36.3% of females and males, respectively. Male and female past-year marijuana users were more likely to have new and multiple sexual partners in the past year (P < 0.05). Past-year marijuana use was associated with prevalent C. trachomatis and/or T. vaginalis infection among females (7.4% vs. 2.9%; PR, 2.57 [95% CI, 1.62–4.07]) and males (4.0% vs. 1.1%; PR, 3.59 [95% CI, 1.96–6.58]), but this association was attenuated after propensity score covariate adjustment among females (aPR, 1.15 [95% CI, 0.72–1.83]) and males (aPR, 2.10 [95% CI, 0.88–5.02]). Additional adjustment for new or multiple sexual partners further attenuated the associations (aPRs, 1.02 [95% CI, 0.65–1.51] and 1.91 [95% CI, 0.82–4.47] for females and males, respectively).

Conclusions

Sexually transmitted infection prevalence was higher among persons with a past-year history of marijuana use; however, this association was not significant after accounting for measured confounders. Additional work is needed to characterize STI prevalence by the mode, duration, and frequency of marijuana use.
Colorectal Adenocarcinomas Harboring ALK Fusion Genes
Authors: Lasota Jerzy , Chłopek Małgorzata , Wasąg Bartosz , Kowalik Artur , Christiansen Jason , Lamoureux Jennifer , Kuźniacka Alina , Felisiak-Gołąbek Anna , Liu Yalan , Reyes Tiffany Ashley R. , Saha Rishabh , Agaimy Abbas , Behenska Kristyna , Biernat Wojciech , Cattaneo Laura , Centonze Giovanni , Daum Ondrej , Daumova Magdalena , Domagała Paweł , Dziuba Ireneusz , Geppert Carol E. , Góźdź Stanisław , Nasierowska-Guttmejer Anna , Hałoń Agnieszka , Hartmann Arndt , Inaguma Shingo , Iżycka-Świeszewska Ewa , Kaczorowski Maciej , Kołos Małgorzata , Kopczyński Janusz , Michal Michal , Milione Massimo , Okoń Krzysztof , Pęksa Rafał , Pyzlak Michał , Ryś Janusz , Waloszczyk Piotr , Wejman Jaroslaw , Miettinen Markku
Published: July 2020

This study determined the frequency and the clinicopathologic and genetic features of colorectal carcinomas driven by oncogenic fusions of the anaplastic lymphoma kinase gene (ALK). Of the 8150 screened tumors, 12 (0.15%) were immunohistochemically ALK-positive with D5F3 antibody. These cancers harbored CAD-ALK (n=1), DIAPH2-ALK (n=2), EML4-ALK (n=2), LOC101929227-ALK (n=1), SLMAP-ALK (n=1), SPTBN1-ALK (n=4), and STRN-ALK (n=1) fusions, as detected by an RNA-based next-generation sequencing assay. ALK fusion carcinomas were diagnosed mostly in older patients with a 9:3 female predominance (median age: 72 y). All tumors, except a rectal one, occurred in the right colon. Most tumors were stage T3 (n=7) or T4 (n=3). Local lymph node and distant metastases were seen at presentation in 9 and 2 patients. These tumors showed moderate (n=6) or poor (n=3) glandular differentiation, solid medullary growth pattern (n=2), and pure mucinous morphology (n=1). DNA mismatch repair–deficient phenotype was identified in 10 cases. Tumor-infiltrating lymphocytes were prominent in 9 carcinomas. In 4 carcinomas, tumor cells showed strong, focal (n=3), or diffuse programmed death-ligand 1 immunoreactivity. CDX2 expression and loss of CK20 and MUC2 expression were frequent. CK7 was expressed in 5 tumors. Four patients died of disease within 3 years, and 7 were alive with follow-up ranging from 1 to 8 years. No mutations in BRAF, RAS, and in genes encoding components of PI3K-AKT/MTOR pathway were identified. However, 1 tumor had a loss-of-function PTEN mutation. Aberration of p53 signaling, TP53 mutations, and/or nuclear accumulation of p53 protein was seen in 9 cases. ALK fusion colorectal carcinomas are a distinct and rare subtype of colorectal cancers displaying some features of mismatch repair–deficient tumors.
Urothelial Carcinomas With Trophoblastic Differentiation, Including Choriocarcinoma
Authors: Przybycin Christopher G. , McKenney Jesse K. , Nguyen Jane K. , Shah Rajal B. , Umar Saleem A. , Harik Lara , Shih Ie-Ming , Cox Roni M.
Published: July 2020

Trophoblastic differentiation (including choriocarcinoma) arising in urothelial carcinoma has been described in numerous case reports, but never in a single series. We present a series of these tumors, describing the morphologic spectrum, applying traditional and novel immunohistochemical stains, and characterizing clinical follow-up. We identified 16 cases, arising predominantly in the bladder (N=14), but also the ureter (N=1) and prostatic urethra (N=1). Six of our cases (38%) contained invasive urothelial carcinoma with admixed syncytiotrophoblasts, 8 cases (50%) consisted of invasive urothelial carcinoma with choriocarcinoma, 1 case (6%) showed urothelial carcinoma in situ with associated choriocarcinoma, and 1 case (6%) consisted of pure choriocarcinoma. Other subtypes of variant morphology were seen in 5 of our cases (31%) and included squamous, glandular, lipoid, chordoid/myxoid, and sarcomatoid features. Given the limited specificity of human chorionic gonadotropin immunohistochemistry, we also studied the expression of a novel specific trophoblastic marker, hydroxyl-δ-5-steroid dehydrogenase, as well as Sal-like protein 4. Human chorionic gonadotropin expression was seen in nearly all cases (93%) but was often not limited to the trophoblastic component, staining the urothelial component also in 85% of the cases. Expression of hydroxyl-δ-5-steroid dehydrogenase was more sensitive and more specific, staining 100% of the cases and limited to trophoblasts in all but 1 case. Sal-like protein 4 expression was variable, staining trophoblast in only 50% of cases and staining the urothelial carcinoma component in 43% of those positive cases. Most of our tumors presented at a high stage and were associated with poor clinical outcomes, with at least muscle-invasive disease (pT2) in 10 of the 14 bladder tumors (71%), periureteric fat invasion in the ureter tumor (pT3), distant metastases in 7 of 16 cases (44%) and death of disease in 3 of the 15 patients with follow-up (20%). Our study describes a series of urothelial carcinomas with trophoblastic differentiation, demonstrating the morphologic spectrum of this entity, its frequent association with other subtypes of variant morphology, its characteristic immunoprofile, and its aggressive clinical behavior.
Specific Biomarker Expression Patterns in the Diagnosis of Residual and Recurrent Endometrial Precancers After Progestin Treatment
Authors: Chen Hao , Lucas Elena , Strickland Amanda L. , Carrick Kelley , Gwin Katja , Castrillon Diego H. , Rivera-Colon Glorimar , Niu Shuang , Molberg Kyle H. , Zheng Wenxin
Published: July 2020

Background:

Conservative management with progestin is a treatment option for atypical hyperplasia (AH). However, pathologic diagnosis of residual/recurrent lesions is often problematic because of the profound morphologic changes induced by progestin and the lack of established diagnostic criteria for progestin-treated residual AH.

Methods:

We conducted a longitudinal study of 265 endometrial biopsies from 54 patients with a history of AH on progestin therapy. Patient outcomes were divided into 3 categories after morphologic review and immunohistochemical staining with phosphatase and tensin homolog (PTEN) and paired box 2 (PAX2): (1) persistent or residual disease; (2) recurrent disease; (3) complete response. All specimens were classified into 3 categories based on morphology: (1) persistent/recurrent disease (nonresponse), (2) morphologically uncertain response, (3) optimally treated (complete response). The staining patterns of PTEN/PAX2 were tracked over time in individual patients and correlated with morphologic findings before and after progestin therapy.

Results:

Our data showed that aberrant expression patterns of PTEN and/or PAX2 were identified in 48 (88.9%) of the 54 primary biopsies and persisted in persistent/recurrent AH across serial endometrial biopsies (n=99, P<0.00001), while normal PTEN and PAX2 expressions were consistently observed in optimally treated cases (n=84, P<0.00001). More importantly, follow-up biopsies that showed a morphologically uncertain response but a PTEN/PAX2 expression pattern identical to the initial biopsy were significantly correlated with persistent or recurrent disease (n=18, P=0.000182), as evidenced by areas with morphologic features diagnostic of AH on subsequent biopsy.

Conclusions:

Biomarker PTEN/PAX2 signatures offer a valuable diagnostic aid to identify residual AH in progestin-treated endometrial samples for which the biomarker status from preprogestin treated AH is known. The findings of this study are promising for a possible future change of diagnostic practice.
Analysis of Risk Factors for Patient Safety Events Occurring in the Emergency Department
Authors: Alsabri Mohamed , Boudi Zoubir , Zoubeidi Taoufik , Alfaki Ibrahim Abdalla , Levy Phillip , Oneyji Churchill , Shan Liu , Camargo Carlos A. , Michel Philippe , Tazarourte Karim , Hachimi-Idrissi Said , Grossman Shamai , Bellou Abdelouahab
Published: July 2020

Objective

The aim of the study was to describe and analyze the risk factors associated with patient safety events (PSEs), defined as adverse events (AEs), preventable AEs (PAEs), and near-miss events (NMEs), in the emergency department (ED).

Methods

It was a retrospective cohort study using ED patients’ data retrieved from January 2010 to December 2016. Quality assurance issues (QAIs) used as triggers included the following: issues during procedural sedation, death within 24 hours of admission, patients’ and physicians’ complaints, returns to the ED within 72 hours, and transfers to an intensive care unit within 24 hours.

Results

Of 383,586 ED visits, 6519 (1.7%) QAIs were reported with a PSEs incidence of 6.1%. Among the 397 PSEs, 258 were AEs including 82 PAEs, and 139 NMEs. During the 7-year period, we observed a fourfold increase in NMEs, and despite a decrease in the rate of AEs with the highest (3.1%) and lowest (0.8%) incidence in 2011 and 2016, respectively, the incidence of PAEs events remained relatively constant. Unadjusted analysis showed that ED waiting time, boarding time, ED length of stay (LOS), ED disposition, as well as diagnostic and QAIs were significantly related to PSEs (P < 0.05). Multivariable analysis showed that the type of QAIs and diagnostic were associated with PSEs (P < 0.001). Type of QAIs was a risk factor for AEs and PAEs occurrence and factors involved in NMEs were type of QAIs (P = 0.02) and ED LOS (P < 0.001). “The odds of a PSE occurring increased by 0.2% for each additional minute increase in the ED waiting time, by 5.2% for each additional boarding hour, and by 4.5% for each ED LOS hour.”

Conclusions

This study showed several potential risk factors for PSEs, especially ED LOS, type of QAIs, and diagnostic. Systematic interventions might have more impact on risk of PSE.
The Incidence and Preventability of Adverse Events in Older Acutely Admitted Patients: A Longitudinal Study With 4292 Patient Records
Authors: Schouten Bo , Merten Hanneke , Spreeuwenberg Peter M. M. , Nanayakkara Prabath W. B. , Wagner Cordula
Published: July 2020

Objectives

Acute care crowding is a global issue, jeopardizing patient safety. An important cause of crowding is the growing number of older, vulnerable, and complex patients. This group is at higher risk of experiencing (preventable) adverse events (AEs) than younger patients.

This study aimed to identify the incidence, preventability, nature, and prevention strategies of AEs in older patients during an acute hospital admission and to assess changes over time.

Methods

We analyzed data of 4292 acutely admitted patients (70+) who died in the hospital, using data of a multicenter Dutch AE record review study (2008, 2012, 2016). Multilevel logistic regression analyses were performed to adjust for patient-mix differences and clustering on department/hospital level per year.

Results

The incidence of AEs in this group declined significantly (χ2(1) = 8.78, P = 0.003) from 10.7% (95% confidence interval [CI] =8.2–13.9) in 2008, 7.4% (95% CI = 5.6–9.7) in 2012, to 7.2% (95% CI = 5.5–9.3) in 2016. The relative preventability showed a significant parabolic trend (χ2(1) = 4.86, P = 0.027), from 46.2% (95% CI = 34.1–58.7), to 32.4% (95% CI = 21.1–46.1), to 44.6% (95% CI = 32–58). Adverse events were often related to medication (26.3% in 2008, 35.1% in 2012, and 39.5% in 2016), and the preventability in AEs related to diagnosis was highest (88.3%, 70.8%, and 79.9%).

Conclusions

The incidence of AEs in older acutely admitted patients declined over the years; however, the preventability increased again after an initial decline. This could be related to crowding or increasing complexity in the acute care chain. Further monitoring and improvement in (preventable) AE rates are necessary to pinpoint areas of improvement to make hospital care for this vulnerable group safer.
Implications of Training Pathways on Future Academic Plastic Surgeon Employment
Authors: Glener Adam D. , Glener Steven R. , Shammas Ronnie L. , Le Elliot , Cason Roger W. , Rezak Kristen , Phillips Brett T.
Published: July 2020

Background

The limited supply of academic plastic surgery positions has led to increased demand and strong competition for these desired positions. Residents and students now seek out academic opportunities earlier in their training to account for this employment shortage. Training pathways and locations play an extremely important role in obtaining an academic position at most institutions. This study aimed to evaluate the training patterns of academic plastic surgeons in an attempt to elucidate its value and role for trainees interested in pursuing future academic careers.

Methods

All full-time faculty members at currently accredited integrated and independent plastic surgery programs were included in the study; clinical affiliates were excluded. These institutions' websites were then queried to obtain the training history of the surgeons meeting inclusion criteria. Data were entered into a centralized database from which descriptive statistics were obtained.

Results

In the 741 surgeons included in the study, 514 (69.4%) completed the independent plastic surgery track and 227 (30.6%) completed the integrated pathway. Residents completing the independent track had 20.8% and 31.7% employment at the same institution where they finished their general and plastic surgery residency, respectively. Of those completing the integrated pathway, 33.9% are employed at the same institution where they graduated from residency. In addition, 47.9% of the surgeons included in the study completed medical school, residency, or fellowship at the current institution at which they are employed. Lastly, 512 surgeons (69.4%) completed at least 1 postresidency fellowship.

Conclusions

Academic surgeons commonly complete a postresidency fellowship and are often employed at institutions where they have formerly trained. Trainees considering an academic career should consider these patterns when planning their future careers.
Biological Glue as an Alternative to Suction Drainage in Tissue-Expanded Flaps in Children
Authors: Bastard François , Seron Aurélie , Vitse Julian , de Berail Ambre , Brigly Thomas , Petiot Dominique , Galinier Philippe , Captier Guillaume
Published: July 2020

Introduction

Biological glue is already used as a hemostatic agent and tissue adhesive in plastic surgery. This study evaluates the use of this glue as an alternative to suction drainage for the adhesion of tissue-expanded flaps in pediatric patients.

Methods

This is a retrospective, multicenter case-control study on 48 flap procedures conducted on 42 children (5 months–12 years of age) between 2004 and 2017, comparing a “glue” group (n = 24) with a control group (n = 24), in which a classic redon drain was used. The control patients were matched according to age, etiology, location of the lesion, and the size of the expander. The primary end point was the duration of hospital stay.

Results

The conditions were 24 cases of congenital nevus, 14 of cicatricial alopecia, and 10 of sebaceous hamartoma. Twenty-nine lesions were located on the scalp, 15 on the back, 2 on the thigh, and 2 on the buttocks.

The average surgical durations (48 ± 24 vs 63 ± 32 minutes, P = 0.13) and average room occupancy time (126 ± 21 vs 139 ± 44 minutes, P = 0.29) were similar between the glue group and the control group. However, the average duration of hospital stay was lower in the glue group (1.5 ± 1.5 days) than in the control group (3.6 ± 1.3 days, P < 0.0001). The complication rates between the groups were similar.

Conclusions

The application of glue on expanded flaps is as reliable as suction drainage with the advantage of reducing the duration of hospital stay and potentially enabling outpatient treatment for certain patients.
Opposite-Running Double Abdominal Flap on Single Pivot Point (Udaipur Flap) for Circumferential Coverage of Wrist and Hand
Authors: Petkar Kiran
Published: July 2020

Complete or near circumferential defects over wrist and hand are difficult situations. They need flaps so long that available adjacent, distant or free flaps often seem inadequate. Hence, this innovative solution was designed. Twin axial flaps were elevated along an oblique axis over abdomen, extending in opposite directions while being pedicled and pivoted at about the same transverse plane. The flaps wrapped the limb from either side and gave complete coverage. Donor sites were closed directly or skin grafted. Three weeks later flap division was done, often after a delay procedure. The technique was used in 6 cases. All patients were young males with history of electrical burns or trauma resulting in total or near circumferential defect. Required length of flaps ranged from 15 to 26 cm with length/breadth ratio ranging from 3:1 to 5:1. Double abdominal flaps could cover all the exposed structures. Limb positioning was comfortable. All flaps survived; all limbs were salvaged. The cover was soft, supple, and pinchable. This is a simple yet effective flap design to address the difficult problem of circumferential defects at hand. The conceptualization and success of this flap system may be attributed to the understanding of patterns of cutaneous vasculature discovered by Ian Taylor. When the vascular axes in a region are known, the same can be exploited to design more than 1 flap in desired orientation. In conclusion, this “Undulate-design Double Abdominal flaps Insertion-Pouch for Upper limb Reconstruction” is a new and effective solution for circumferential defects of wrist and hand.
Peroral Endoscopic Diverticulotomy (POED) for Zenker Diverticulum Using Submucosal Injection to Perform a Complete Myotomy
Authors: Pugliese Francesco , Dioscoridi Lorenzo , Italia Angelo , Forgione Antonello , Cintolo Marcello , Forti Edoardo , Bonato Giulia , Massad Mutaz , Mutignani Massimiliano
Published: July 2020

Endoscopic diverticulotomy associated with cricopharyngeal myotomy is a well-known and safe treatment for Zenker diverticulum. We describe our first 5 consecutive cases treated by a new variant of the technique that allows a deeper and longer myotomy than the standard one. Technical success was achieved in all the cases. All patients showed a significant improvement and relevant disappearance of preoperative dysphagia. Tips for the technique are described in the paper. This variant of peroral endoscopic diverticulotomy for Zenker diverticulum is feasible, effective, and guarantees a complete myotomy in selected patients.
Evaluating the Prevalence of Pelvic Floor Disorders in Women in Nonmetropolitan Communities
Authors: Khan Aqsa , Zhang Nan , Carolan Alexandra , Tay Kimberly , Wolter Christopher
Published: July 2020

Introduction

Prevalence rates of pelvic floor disorders in women in nonmetropolitan communities compared with metropolitan communities are unknown. We hypothesize that the rates are higher in women in nonmetropolitan communities.

Methods

We accessed the health survey data from the NHANES (National Health and Nutrition Examination Survey) from 2009 to 2010 divided by geocodes into nonmetropolitan (<50,000 inhabitants) and metropolitan communities (>50,000). Responses were analyzed for the following conditions: urinary incontinence and nocturia, bowel urgency and anal incontinence, and symptomatic vaginal bulge. Age-adjusted prevalence rates were estimated using logistic regression.

Results

The 2009–2010 NHANES survey was completed nationwide by 302 women in nonmetropolitan communities and 2201 women in metropolitan communities. Overall, prevalence rates of PFDs did not significantly differ between groups. Prevalence rates of urinary incontinence and nocturia at least weekly were similar between metropolitan and nonmetropolitan groups (16.2% vs 14.6%, P = 0.47), with stress incontinence being more common than urgency and other types of incontinence (40% vs 23% and 8%). Women in metropolitan communities reported more bowel urgency than women in nonmetropolitan communities (33.3% vs 26.8%, P = 0.02); however, prevalence rates between both groups are similar with regards to anal incontinence at least once a month or more (9.2% vs 9.0%, P = 0.76). Prolapse symptoms were also not significantly different between the groups (2.4% in both). There was an increase in prevalence in each of the pelvic floor disorder symptoms with age.

Conclusions

Pelvic floor disorders are prevalent and increase with age in women in nonmetropolitan communities at rates similar to women in metropolitan communities.
Structure, space and size: competing drivers of variation in urban and rural measles transmission
Authors: Korevaar Hannah , Metcalf C. Jessica , Grenfell Bryan T.
Published: July 2020

A key concern in public health is whether disparities exist between urban and rural areas. One dimension of potential variation is the transmission of infectious diseases. In addition to potential differences between urban and rural local dynamics, the question of whether urban and rural areas participate equally in national dynamics remains unanswered. Specifically, urban and rural areas may diverge in local transmission as well as spatial connectivity, and thus risk for receiving imported cases. Finally, the potential confounding relationship of spatial proximity with size and urban/rural district type has not been addressed by previous research. It is rare to have sufficient data to explore these questions thoroughly. We use exhaustive weekly case reports of measles in 954 urban and 468 rural districts of the UK (1944–1965) to compare both local disease dynamics as well as regional transmission. We employ the time-series susceptible–infected–recovered model to estimate disease transmission, epidemic severity, seasonality and import dependence. Congruent with past results, we observe a clear dependence on population size for the majority of these measures. We use a matched-pair strategy to compare proximate urban and rural districts and control for possible spatial confounders. This analytical strategy reveals a modest difference between urban and rural areas. Rural areas tend to be characterized by more frequent, smaller outbreaks compared to urban counterparts. The magnitude of the difference is slight and the results primarily reinforce the importance of population size, both in terms of local and regional transmission. In sum, urban and rural areas demonstrate remarkable epidemiological similarity in this recent UK context.
Quantifying the spatial pattern of dialect words spreading from a central population
Authors: Takahashi Takuya , Ihara Yasuo
Published: July 2020

Some dialect words are shared among geographically distant groups of people without close interaction. Such a pattern may indicate the current or past presence of a cultural centre exerting a strong influence on peripheries. For example, concentric distributions of dialect variants in Japan may be explicable by repeated inventions of new variants at Kyoto, the ancient capital, with subsequent outward diffusion. Here we develop a model of linguistic diffusion within a population network to quantify the distribution of variants created at the central population. Equilibrium distributions of word ages are obtained for idealized networks and for a realistic network of Japanese prefectures. Our model successfully replicates the observed pattern, supporting the notion that a centre–periphery social structure underlies the emergence of concentric patterns. Unlike what has previously been claimed, our model indicates that a novelty bias in linguistic transmission is not always necessary to account for the concentric pattern, whereas some bias in the direction of transmission between populations is needed to be consistent with the observed absence of old words near the central population. Our analysis on the realistic network also suggests that the process of linguistic transmission was not much affected by between-prefecture differences in population size.
Polyethylene-like materials from plant oils
Authors: Mecking Stefan
Published: July 2020

Polyethylene (PE) is the most important synthetic polymer material produced. Its excellent material properties arise from crystalline interactions in its hydrocarbon chains. This simple concept inspires studies of materials based on alternative non-fossil feedstocks and with additional traits such as a non-persistent nature. Renewable seed oil or microalgae oil lipids can serve as a feedstock for long-chain difunctional monomers. Catalytic conversion of their unsaturated fatty acids by e.g. isomerizing carbonylation or olefin metathesis yields long-chain monomers X-(CH
2
)
n
-X with 18–26 carbon atoms and terminal dicarboxy, diol or diamine groups (X), and ultralong-chain PE telechelics with 48 carbon atoms. These can be polymerized to polyesters, polycarbonates and other (ultra)long-chain polycondensates. These in many cases possess PE-like solid-state structure and properties. Unlike PE, they contain in-chain functional groups that can potentially enhance degradability. The crystalline and hydrophobic nature of the polymers decelerates degradation strongly compared to rapidly degrading shorter chain analogues. Our preliminary findings suggest that a non-persistent nature can be achieved for these materials. This review article is based on a lecture held at the Royal Society Discussion Meeting on Science to enable the circular economy.

This article is part of a discussion meeting issue ‘Science to enable the circular economy’.
Sustainable catalytic rearrangement of terpene-derived epoxides: towards bio-based biscarbonyl monomers
Authors: Löser P. S. , Rauthe P. , Meier M. A. R. , Llevot A.
Published: July 2020

Seeking a sustainable and selective approach for terpene modification, a catalyst deconvolution approach was applied to the Meinwald rearrangement of (+)-limonene oxide as a model substrate to yield dihydrocarvone. In order to identify the most suitable catalyst and reaction conditions, different Lewis acids were evaluated. Bismuth triflate proved to be the most active catalyst under mild reaction conditions, with a low catalyst loading (1 mol%) and a relatively short reaction time (3 h). The optimized reaction conditions were subsequently transferred to other terpene-based epoxides, yielding different bio-based biscarbonyl structures, which constitute interesting and valuable substances, e.g. for polymer synthesis or as fragrances. Monoepoxides derived from (
R
)-(−)-carvone and (+)-dihydrocarvone rearranged to the desired products with high selectivities and yields. γ-Terpinene dioxide could be transformed in a double rearrangement to the respective biscarbonyl in moderate yields. A better result was achieved for limonene dioxide after further adjustment of the protocol to reach acceptable yields with a low catalyst loading of 0.1 mol% using 2-methyl tetrahydrofuran as a sustainable solvent. Compared to many procedures described in the literature, this procedure represents a step towards an increased sustainability in terpene modification by considering several principles of Green Chemistry, such as renewable resources, catalysis and mild reaction conditions for elementary chemical transformations.

This article is part of a discussion meeting issue ‘Science to enable the circular economy’.
Plastics as a materials system in a circular economy
Authors: Bucknall David G.
Published: July 2020

Plastics have transformed our modern world. With a range of outstanding properties, they are used in an ever-widening range of applications. However, the linear economy of their use means that a large volume of plastics is discarded after use. It is believed that approximately 80% of the estimated total 6.3 Bt of plastics ever produced have been discarded, representing not only a huge loss of valuable resources, but mismanaged waste is also the origin of an ever-increasing environmental disaster. Strategies to prevent loss of materials resources and damage to the environment are elements of a circular plastics economy that aims to maintain plastics at their highest value for the longest time possible and at the same time improve the economy and prevent detrimental environmental impact. The latter in particular is driving recent changes in policies and legislation across the world that are rapidly being introduced in order to solve these environmental issues. The achievement of a circular economy will require not only innovative technical developments, but also major economic investment and changes to business practice coupled with significant changes in social behaviour. This paper summarizes the complex and highly interrelated technical issues and provides an overview of the major challenges, potential solutions and opportunities required to achieve and operate a circular plastics economy.

This article is part of a discussion meeting issue ‘Science to enable the circular economy’.
Biocatalysis and biomass conversion: enabling a circular economy
Authors: Sheldon Roger A.
Published: July 2020

This paper is based on a lecture presented to the Royal Society in London on 24 June 2019. Two of the grand societal and technological challenges of the twenty-first century are the ‘greening' of chemicals manufacture and the ongoing transition to a sustainable, carbon neutral economy based on renewable biomass as the raw material, a so-called bio-based economy. These challenges are motivated by the need to eliminate environmental degradation and mitigate climate change. In a bio-based economy, ideally waste biomass, particularly agricultural and forestry residues and food supply chain waste, are converted to liquid fuels, commodity chemicals and biopolymers using clean, catalytic processes. Biocatalysis has the right credentials to achieve this goal. Enzymes are biocompatible, biodegradable and essentially non-hazardous. Additionally, they are derived from inexpensive renewable resources which are readily available and not subject to the large price fluctuations which undermine the long-term commercial viability of scarce precious metal catalysts. Thanks to spectacular advances in molecular biology the landscape of biocatalysis has dramatically changed in the last two decades. Developments in (meta)genomics in combination with ‘big data’ analysis have revolutionized new enzyme discovery and developments in protein engineering by directed evolution have enabled dramatic improvements in their performance. These developments have their confluence in the bio-based circular economy.

This article is part of a discussion meeting issue ‘Science to enable the circular economy'.
Biomass hydrodeoxygenation catalysts innovation from atomistic activity predictors
Authors: Morteo-Flores Fabian , Engel Julien , Roldan Alberto
Published: July 2020

Circular economy emphasizes the idea of transforming products involving economic growth and improving the ecological system to reduce the negative consequences caused by the excessive use of raw materials. This can be achieved with the use of second-generation biomass that converts industrial and agricultural wastes into bulk chemicals. The use of catalytic processes is essential to achieve a viable upgrade of biofuels from the lignocellulosic biomass. We carried out density functional theory calculations to explore the relationship between 13 transition metals (TMs) properties, as catalysts, and their affinity for hydrogen and oxygen, as key species in the valourization of biomass. The relation of these parameters will define the trends of the hydrodeoxygenation (HDO) process on biomass-derived compounds. We found the hydrogen and oxygen adsorption energies in the most stable site have a linear relation with electronic properties of these metals that will rationalize the surface's ability to bind the biomass-derived compounds and break the C–O bonds. This will accelerate the catalyst innovation for low temperature and efficient HDO processes on biomass derivates, e.g. guaiacol and anisole, among others. Among the monometallic catalysts explored, the scaling relationship pointed out that Ni has a promising balance between hydrogen and oxygen affinities according to thed-band centre andd-band width models. The comparison of the calculated descriptors to the adsorption strength of guaiacol on the investigated surfaces indicates that thed-band properties alone are not best suited to describe the trend. Instead, we found that a linear combination of work function andd-band properties gives significantly better correlation.

This article is part of a discussion meeting issue ‘Science to enable the circular economy’.
Octane isomer dynamics in H-ZSM-5 as a function of Si/Al ratio: a quasi-elastic neutron scattering study
Authors: O'Malley Alexander J. , García Sakai Victoria , Dimitratos Nikolaos , Jones Wilm , Catlow C. Richard A. , Parker Stewart F.
Published: July 2020

Dynamical behaviour of
n-
octane and 2,5-dimethylhexane in H-ZSM-5 zeolite catalysts of differing Si/Al ratios (15 and 140) was probed using quasi-elastic neutron scattering, to understand molecular shape and Brønsted acid site density effects on the behaviour of common species in the fluid catalytic cracking (FCC) process, where H-ZSM-5 is an additive catalyst. Between 300 and 400 K,
n
-octane displayed uniaxial rotation around its long axis. However, the population of mobile molecules was larger in H-ZSM-5(140), suggesting that the lower acid site concentration allows for more molecules to undergo rotation. The rotational diffusion coefficients were higher in H-ZSM-5(140), reflecting this increase in freedom. 2,5-dimethylhexane showed qualitative differences in behaviour to
n
-octane, with no full molecule rotation, probably due to steric hindrance in the constrictive channels. However, methyl group rotation in the static 2,5-dimethylhexane molecules was observed, with lower mobile fractions in H-ZSM-5(15), suggesting that this rotation is less hindered when fewer Brønsted sites are present. This was further illustrated by the lower activation barrier calculated for methyl rotation in H-ZSM-5(140). We highlight the significant immobilizing effect of isomeric branching in this important industrial catalyst and show how compositional changes of the zeolite can affect a range of dynamical behaviours of common FCC species upon adsorption.

This article is part of a discussion meeting issue ‘Science to enable the circular economy’.
Ranking Radiology Residency Programs: What Medical Students Think is Important Versus What Residents Say is Important
Authors: Rios Florentino Saenz , Alwan Shadan , Nguyen Quan
Published: July 2020

Background

Matching to a residency is a great success, but it is also a significant change in the lives of many graduating medical students. It is expected that during this time, many priorities may change, especially after participation in a residency program where residents are further exposed to the dynamics of the program.

Purpose

There are no current studies that attempt to determine what factors residents prefer after the match.

Methods

This study was an anonymous study conducted through an online survey. The survey asked two open-ended questions asking the survey taker to list four factors in order of importance that they considered important in a program, one as an MS4 and one as a resident. Results were compiled, tallied, and categorized to find common themes between the applicant’s preferences through descriptive statistics.

Results

Of the 24 surveys sent out, a total of 15 applicants responded for a response rate of 62.5%. The most common preferences among both MS4s were “Work Environment” and “Location,” however, factors like “Education” and “Faculty: Resident Ratio” was seen as increasing in importance among residents.

Conclusion

While an increase was seen in some factors (Education, Faculty:Residency Ratio, and Program Size), the general trend of preferences going from MS4 to a resident was more spread-out in the distribution of what residents considered essential factors. Education involves both formal didactics and readout of dictated exams. Higher Faculty:Residency affects education because more faculty decreases the clinical workload of each faculty and leaves the faculty more time for teaching. Larger program size decreases the amount of call burdern per resident.
Recurrent respiratory viral diseases and chronic sequelae due to dominant negative IFIH1
Authors: Deal Christin L , Thauland Timothy J , Signer Rebecca , Nelson Stanley F ,   Undiagnosed Diseases Network, Lee Hane , Butte Manish J
Published: July 2020

Viral respiratory infections are the most common childhood infection worldwide. However, even common pathogens can have significant consequences in the context of patients with primary immunodeficiency diseases. More than half or viral infections annually are due to rhinovirus/enterovirus strains. Most clinical manifestations of viral infection are mild. However 3% of cases result in hospitalization in patients who have no other known risk factors. These patients may have an inborn error of immunity, a genetic susceptibility to viral infections. Here we present the case of an adult male who suffered respiratory viral infections his whole life and developed chronic, inflammatory damage to sinuses and lungs as a consequence. Genomic sequencing identified compound heterozygous variants in the IFIH1 gene, encoding the protein Melanoma Differentiation Association Protein 5 (MDA5), a RIG-I-like cytoplasmic sensor of RNA intracellular infections. We show a dominant negative effect on these variants on the level of interferon-induced expression of MDA5 protein. This work supports that loss-of-function variants in IFIH1 affect the sensing of viral infections. Underlying genomic variants may dictate the point at which recurrent, respiratory viral infections leave commonplace experience and incur lasting damage.
Maternal biomarkers for early prediction of the neural tube defects pregnancies
Authors: Yadav Upendra , Kumar Pradeep , Rai Vandana
Published: July 2020

Neural tube defects (NTD) are the most common congenital birth defects. The reason for the NTD cause is still not completely known, but it is believed that some genetic and environmental factors might play a role in its etiology. Among the genetic factors the polymorphism in the folate gene pathway is crucial. Numerous studies have suggested the possible role of maternal higher plasma concentration of homocysteine and low concentration of folate and cobalamin in the development of NTD but some negative studies are also published. So, in this study, authors tried to find out the exact relation between NTD and maternal biomarkers like folate, cobalamin and homocysteine by conducting a meta-analysis. Different electronic databases were searched for the eligible studies. Standardized mean difference (SMD) with 95% confidence interval (CI) was used to determine association between maternal markers as risk for NTD pregnancy. The p value <0.05 was considered statistically significant in all tests. All the statistical analyses were done in the Open Meta-Analyst program. The homocysteine is significantly associated with the increased risk of NTD (SMD= 0.57; 95% CI: 0.35-0.80, p= <0.001; I2= 93.01%), s-folate showed protective role in NTD (SMD= −0.48; 95% CI: −0.77 to −0.19, p= 0.001; I2= 95.73%), similarly cobalamin is also having protective role (SMD= −0.28; 95% CI: −0.43 to −0.13, p= <0.001; I2= 80.40%). In conclusion this study suggest that different maternal biomarkers may be used for the early prediction of the NTDs.
Improving US Virgin Islands’ heath system: “You get more benefits with your insurance in the States than you get here”
Authors: Wang Karen H. , Hendrickson Zoé M. , Friedman Hannah R. , Nunez Maxine A. , Nunez-Smith Marcella
Published: July 2020

Background

The US Virgin Islands (USVI) are actively rebuilding their healthcare delivery system following destruction by Hurricanes Irma and Maria in 2017.

Methods

In 2013, we conducted a qualitative study in the US Virgin Islands using semi-structured one-on-one interviews to explore individuals’ decision-making regarding healthcare-seeking off-island. The coding team analyzed the transcripts using a constant comparative analysis, and Atlas.ti to organize our emerging thematic analysis.

Results

Five themes emerged from 19 interviews that illustrate healthcare system level factors that influence participants’ decisions about seeking healthcare off-island: 1) limited availability of services and desire for options, 2) limited accessibility of services, 3) healthcare system interactions and experiences, 4) healthcare system policies, and 5) trust in healthcare systems.

Conclusions

The experiences of care seeking off-island for our sample highlight several mechanisms through which the USVI healthcare delivery system could improve, including the adoption of telemedicine, changes in insurance, and healthcare workforce policies.
Artificial Intelligence-Enabled, Fully Automated Detection of Cardiac Amyloidosis Using Electrocardiograms and Echocardiograms
Authors: Goto Shinichi , Mahara Keitaro , Beussink-Nelson Lauren , Ikura Hidehiko , Katsumata Yoshinori , Endo Jin , Gaggin Hanna K. , Shah Sanjiv J. , Itabashi Yuji , MacRae Calum A , Deo Rahul C
Published: July 2020

Although individually uncommon, rare diseases collectively affect over 350 million patients worldwide and are increasingly the target of therapeutic development efforts1. Unfortunately, the pursuit and use of such therapies have been hindered by a common challenge: patients with specific rare diseases are difficult to identify, especially if the conditions resemble more prevalent disorders. Cardiac amyloidosis is one such rare disease, which is characterized by deposition of misfolded proteins within the heart muscle resulting in heart failure and death2–4. In recent years, specific therapies have emerged for cardiac amyloidosis5,6and several more are under investigation7–9, but because cardiac amyloidosis is mistaken for common forms of heart failure, it is typically diagnosed late in its course. As a possible solution, artificial intelligence methods could enable automated detection of rare diseases, but model performance must address low disease prevalence. Here we present an automated multi-modality pipeline for cardiac amyloidosis detection using two neural-network models; one using electrocardiograms (ECG) and the second using echocardiographic videos as input. These models were trained and validated on 3 and 5 academic medical centers (AMC), respectively, in the United States and Japan. Both models had excellent accuracy for detecting cardiac amyloidosis with C-statistics of 0.85-0.92 and 0.91-1.00 for the ECG and echocardiography models, respectively, with the latter outperforming expert diagnosis. Simulating deployment on 13,906 and 7,775 patients with ECG-echocardiography paired data for AMC2 and AMC3 indicated a positive predictive value (PPV) for the ECG model of 4% and 3% at 61% and 54% recall, respectively. Pre-screening with ECG enhanced the echocardiography model performance from PPV 23% and 20% to PPV 58% and 53% at 64% recall, respectively for AMC2 and AMC3. In conclusion, we have developed a robust pipeline to augment detection of cardiac amyloidosis, which should serve as a generalizable strategy for other rare and intermediate frequency cardiac diseases with established or emerging therapies.
Impact of Viz LVO on Time-to-Treatment and Clinical Outcomes in Large Vessel Occlusion Stroke Patients Presenting to Primary Stroke Centers
Authors: Morey Jacob R. , Fiano Emily , Yaeger Kurt A. , Zhang Xiangnan , Fifi Johanna T.
Published: July 2020

Introduction

Randomized controlled trials have demonstrated the importance of time-to-treatment on clinical outcomes in large vessel occlusion (LVO) stroke. Delays in interventional radiology (INR) consultation are associated with a significant delay in overall time to endovascular treatment (EVT). Delays in EVT are particularly prevalent in Primary Stroke Centers (PSC), hospitals without thrombectomy capability onsite, where the patient requires transfer to a Thrombectomy Capable or Comprehensive Stroke Center for EVT. A novel computer aided triage system, Viz LVO, assists in early notification of the PSC stroke team and affiliated INR team. This platform includes an image viewer, communication system, and an artificial intelligence algorithm that automatically identifies suspected LVO strokes on CTA imaging and rapidly triggers alerts.

Hypothesis

Viz LVO will decrease time-to-treatment and improve clinical outcomes.

Methods

A prospectively maintained database was assessed for all patients who presented to a PSC currently utilizing Viz LVO in the Mount Sinai Health System in New York and underwent EVT following transfer for LVO stroke between October 1, 2018 and March 15, 2020. There were 42 patients who fit the inclusion criteria and divided into pre- and post-Viz ContaCT implementation by comparing the periods of October 1, 2018, to March 15, 2019, “Pre-Viz”, and October 1, 2019, to March 15, 2020, “Post-Viz.” Time intervals and clinical outcomes were collected and compared.

Results

The Pre- and Post-Viz cohorts were similar in terms of gender, age, proportion receiving IV-tPA, and proportion with revascularization of TICI > 2B. The presenting NIHSS and pre-stroke mRS scores were not statistically different.

The median initial door-to-INR notification was significantly faster in the post-Viz cohort (21.5 minutes vs 36 minutes; p=0.02). The median initial door-to-puncture time interval was 20 minutes shorter in the Post-Viz cohort, but this was not statistically significant (p=0.20).

The 5-day NIHSS and discharge mRS were both significantly lower in the Post-Viz cohort (p=0.02 and p=0.03, respectively). The median 90-day mRS scores were also significantly lower post-Viz implementation, although a similar proportion received a good outcome (mRS score ≤ 2) (p=0.02 and p=0.42, respectively).

Conclusions

EVT is a time-sensitive intervention that is only available at select stroke centers. Significant delays in time-to-treatment are present when patients require transfer from PSCs to a EVT capable stroke center. In a large health care system, we have shown that Viz LVO implementation is associated with improved time to INR notification and clinical outcomes. Viz LVO has the potential for wide-spread improvement in clinical outcomes with implementation across large hub and stroke systems across the country.