bluuebunny/crossref_metadata_2025 huggingface dataset:
Generative adversarial networks in ophthalmology: what are these and how can they be used?
Authors: Wang Zhaoran , Lim Gilbert , Ng Wei Yan , Keane Pearse A. , Campbell J. Peter , Tan Gavin Siew Wei , Schmetterer Leopold , Wong Tien Yin , Liu Yong , Ting Daniel Shu Wei
Published: July 2021

Purpose of review

The development of deep learning (DL) systems requires a large amount of data, which may be limited by costs, protection of patient information and low prevalence of some conditions. Recent developments in artificial intelligence techniques have provided an innovative alternative to this challenge via the synthesis of biomedical images within a DL framework known as generative adversarial networks (GANs). This paper aims to introduce how GANs can be deployed for image synthesis in ophthalmology and to discuss the potential applications of GANs-produced images.

Recent findings

Image synthesis is the most relevant function of GANs to the medical field, and it has been widely used for generating ‘new’ medical images of various modalities. In ophthalmology, GANs have mainly been utilized for augmenting classification and predictive tasks, by synthesizing fundus images and optical coherence tomography images with and without pathologies such as age-related macular degeneration and diabetic retinopathy. Despite their ability to generate high-resolution images, the development of GANs remains data intensive, and there is a lack of consensus on how best to evaluate the outputs produced by GANs.

Although the problem of artificial biomedical data generation is of great interest, image synthesis by GANs represents an innovation with yet unclear relevance for ophthalmology.
Evaluation of Door-to-Balloon Times After Implementation of a ST-Segment Elevation Myocardial Infarction Network
Authors: Evers Julianne M. , York Nancy L. , Owens Heather , Hardin-Pierce Melanie G.
Published: July 2021

Background

ST-segment elevation myocardial infarction (STEMI) requires prompt therapy. It is recommended for door-to-balloon (DTB) times to be less than 90 minutes. In the United States, some locations have difficulty meeting this goal.

Objective

The objective of this study was to determine whether implementation of a STEMI network decreased DTB times at a large, STEMI-receiving, metropolitan academic hospital in the southeastern United States. Furthermore, differences among presentation types, including walk-in, emergency medical services, and transfers, were explored.

Methods

A pre-post time series study of electronic medical record data was conducted to evaluate the efficacy of a STEMI network.

Results

The sample included 127 patients with a diagnosis of STEMI, collected during 3 periods (T1, T2, and T3). Patients were primarily White (78.0%) and male (67.7%), with a mean (SD) age of 58.9 (13.9) years. The 1-way analysis of variance revealed a significant difference in overall DTB times, F
2 = 11.66, P < .001. Post hoc comparisons indicated longer mean DTB times for T1 compared with T3 (P < .001) and T2 (P < .001). When exploring presentation type, 1-way analysis of variance revealed a significant difference in mean DTB times in transfer patients between T1 and T2 (P < .001) and T1 to T3 (P < .001). No other statistical differences were noted; however, all DTB times with the exception of T2 for emergency medical services presentation decreased.

Conclusions

Implementation of a STEMI network was effective at decreasing overall DTB times with patients who presented to the hospital with a diagnosis of STEMI.
Characteristics of Patients Who Do Not Respond to Motivational Interviewing for Heart Failure Self-care
Authors: Stawnychy Michael A. , Zeffiro Valentina , Iovino Paolo , Vellone Ercole , Riegel Barbara
Published: July 2021

Background

Motivational interviewing (MI) improves heart failure (HF) self-care for most yet fails to work for some patients. Identifying patients less likely to benefit from MI would save time in identifying a more suitable treatment for these patients.

Objective

The aim of this study was to identify the characteristics of adults with HF less likely to clinically improve self-care after MI.

Methods

This was a secondary intervention group analysis (n = 230) of MOTIVATional intErviewing to improve self-care in Heart Failure patients (MOTIVATE-HF), a trial evaluating MI in improving HF self-care maintenance and management. Self-care was measured with the Self-care of Heart Failure Index v. 6.2 at baseline and 3 months from enrollment. Participants were dichotomized into MI nonresponder (standardized score change <8 points) or MI responder (score change ≥8 points). Logistic regression, adjusted for group differences, identified determinants of nonresponse (odds ratio [95% confidence interval]).

Results

Significant risk factors for self-care maintenance nonresponse 3 months after the intervention were nonischemic HF (2.58 [1.33–5.00], P = .005) and taking fewer medications (0.83 [0.74–0.93], P = .001). These variables explained 29.6% of the variance in HF self-care maintenance. Risk factors for self-care management nonresponse were living alone (4.33 [1.25–14.95], P = .021) and higher baseline self-care management (1.06 [1.02–1.09], P < .001), explaining 35% of the variance in HF self-care management.

Conclusions

Motivational interviewing may be less beneficial in patients with nonischemic HF and taking fewer medications. Patients with HF living alone with relatively better self-care management may be at risk for MI treatment failure. Identifying characteristics of nonresponders to MI in HF contributes to clinical decision making and personalized interventions.
Extracorporeal Membrane Oxygenation Support for Antineutrophil Cytoplasmic Antibody-associated Vasculitides: An ELSO Registry Analysis
Authors: O’Neil Erika R. , Quinn Rachel E. , Olson Taylor L. , Rycus Peter T. , Anders Marc M. , Chartan Corey A. , Vogel Tiphanie P. , Silva-Carmona Manuel , Coleman Ryan D.
Published: July 2021

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides with pulmonary involvement include granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis, and can present with life-threatening pulmonary hemorrhage in up to 40% of patients. Mortality in those patients who require intubation and mechanical ventilation can reach 77%. Extracorporeal membrane oxygenation (ECMO) can be used to support these patients through definitive diagnosis and treatment, although minimizing the risk of ventilator-induced lung injury. We aimed to determine factors associated with favorable outcomes in patients with (ANCA)-associated vasculitides supported on ECMO. We performed a retrospective observational study using the Extracorporeal Life Support Organization registry of pediatric and adult patients with ANCA-associated vasculitis supported on ECMO from 2010 to 2020. One hundred thirty-five patients were included for analysis. Many patients had renal involvement (39%) in addition to pulmonary involvement (93%). Survival was 73% in AAV patients supported on ECMO. The presence of pulmonary hemorrhage was not associated with worse outcomes in our cohort. Older age, the use of venoarterial ECMO, ECMO-cardiopulmonary resuscitation, or sustaining a cardiac arrest before ECMO was associated with decreased survival. In conclusion, venovenous ECMO should be considered as a supportive bridge to definitive diagnosis and treatment in (ANCA)-associated vasculitides, regardless if pulmonary hemorrhage is present.
Radiographic outcomes of femur fractures following SIGN Fin nailing in low- and middle-income countries
Authors: Birner Zachary H. , Hetzel Scott J. , Wilson Nathaniel M. , Whiting Paul S.
Published: July 2021

Objective:

To measure the effectiveness of the Surgical Implant Generation Network (SIGN) Fin nail for achieving satisfactory postoperative radiographic alignment following femoral shaft fractures.

Methods:

Femoral shaft fractures stabilized with the SIGN Fin nail were identified using the SIGN Online Surgical Database. A random number generator was used to identify 500 femur fractures fixed within 6 weeks of injury for which postoperative radiographs were available. Fractures were classified using OTA/AO and Winquist-Hansen classification systems. Deviation from anatomic alignment was measured on anterior-posterior and lateral radiographs using an on-screen protractor tool. Other clinical variables recorded in the SIGN Online Surgical Database were also analyzed. Simple logistic regression was used to assess for associations between subject and surgical characteristics and misalignment status. Intra- and inter-rater agreement was assessed with intraclass correlation coefficient (ICC).

Results:

The overall rate of malalignment >5° was 9.4%. Factors associated with increased incidence of malalignment include older age, increased time to surgery, distal diaphyseal location, closed (vs open) reduction, degree of comminution, and fracture classification. Intra-rater ICC was 0.70 (0.52, 0.82) in the coronal plane and 0.55 (0.32, 0.72) in the sagittal plane. Inter-rater ICC was 0.37 (0.08, 0.60) and 0.32 (0.05, 0.54), respectively.

Conclusion:

The SIGN Fin nail is an effective implant for fixation of femoral shaft fractures in resource-limited regions, achieving rates of satisfactory postoperative alignment comparable to that of the standard SIGN nail as well as femoral shaft fractures treated in North American Trauma Centers. Further research is required to investigate rotational alignment and long-term clinical outcomes for the SIGN Fin nail.

Level of evidence:

IV.
Adoption of Telehealth by Pediatric Physical Therapists During COVID-19: A Survey Study
Authors: Hall Jamie B. , Luechtefeld Jessica T. , Woods Morgan L.
Published: July 2021

Purpose:

To describe the characteristics of pediatric physical therapy telehealth practice during COVID-19.

Methods:

An anonymous, online survey was distributed to pediatric physical therapists (PTs) in the United States who transitioned to telehealth during COVID-19.

Results:

Two hundred five respondents completed all quantitative questions. Ninety-six percent reported never providing telehealth previously and only 14.6% had formal training. More than 35% reported 76% to 100% of their caseload transitioned to telehealth. Most respondents perceived that telehealth was somewhat or very effective for caregivers (90.3%) and children (77.1%) and felt somewhat or very confident providing telehealth (73.2%). However, those practicing in school-based settings rated perceived effectiveness and confidence lower than PTs in other settings. Ultimately, 76.1% of respondents would consider providing telehealth in the future.

Conclusion:

The forced transition of pediatric PTs to the telehealth model during the COVID-19 pandemic resulted in positive experiences for many, supporting wider adoption in the future.
Distal Gracilis Tear in an Equestrian
Authors: Chen Ya-Ting , Mills Catherine , von Rickenbach Kristian J. , McInnis Kelly C.
Published: July 2021

A 61-yr-old female equestrian presented after 2 wks of left medial thigh pain, which developed suddenly while exiting a car. She denied any history of recent trauma or falls. On examination, she was found to have tenderness at the left distal medial thigh with a palpable region of decreased tissue volume at the gracilis myotendinous junction. Point-of-care ultrasound and magnetic resonance imaging confirmed a high-grade partial thickness tear of the left distal gracilis at the myotendinous junction, as well as pes anserine bursal distention. She received physical therapy and underwent a 1-time ultrasound-guided corticosteroid injection to the left pes anserine bursa. At follow-up, her symptoms had significantly improved, and she had returned to horseback riding after 12 wks. Isolated gracilis myotendinous tear is a rare condition, and this is a unique case with an atypical mechanism of injury as gracilis injuries have only been reported during vigorous exercise-related activities rather than transitional movements. This case illustrates the potential increased risk of distal gracilis injury after repetitive corticosteroid injections (genicular nerve blocks and radiofrequency lesioning) in a patient who was also likely predisposed to gracilis microtrauma due to her equestrian activities. Gracilis injury should be considered in the differential diagnosis of distal medial thigh pain, especially in cases with similar interventional and recreational profiles.
Characterization of Medication Errors in a Medical Intensive Care Unit of a University Teaching Hospital in South Korea
Authors: Yoon Jimin , Yug Ji Seob , Ki Dae Yun , Yoon Ji-Eun , Kang Sung Wook , Chung Eun Kyoung
Published: July 2021

Objectives

The objective of this study was to characterize the current status of medication errors (MEs) throughout the medication therapy process from prescribing to use and monitoring in a medical intensive care unit (MICU) in Korea.

Methods

Four trained research pharmacists collected data through retrospectively reviewing electronic medical records for adults hospitalized in the MICU in 2017. The occurrence of MEs was determined through interprofessional team discussion led by an academic faculty pharmacist and a medical intensivist based on the medication administration records (MARs). The type of MEs and the consequent ME-related outcome severity were categorized according to the Pharmaceutical Care Network Europe and the National Coordinating Council for Medication Error Reporting and Prevention, respectively.

Results

Overall, electronic medical records for 293 patients with 78,761 MARs were reviewed in this study. At least one type of ME occurred in 271 patients (92.5%) in association with 16,203 MARs (21%), primarily caused by inappropriate dose (35.5%), drug (27.8%), and treatment duration (25.1%). Clinically significant harmful events occurred in 24 patients (8%), including life-threatening (n = 5) and death (n = 2) cases. The 2 patients died of enoxaparin-induced fatal hemorrhage and neutropenia associated with ganciclovir and cefepime. Antibiotics were the most common culprit medications leading to clinically significant harmful events.

Conclusions

In conclusion, MEs are prevalent in the MICU in Korea, most commonly prescribing errors. Although mostly benign, harmful events including deaths may occur due to MEs, mainly associated with antibiotics. Systematic strategies to minimize these potentially fatal MEs are urgently needed.
Can Subclinical Atherosclerosis Be Assessed More Precisely in Behçet Syndrome Patients by Using a Particular Cutoff Value for Carotid Intima Media Thickness?
Authors: Uslu Yurteri Emine , Üstüner Evren , Torgutalp Murat , Yayla Müçteba Enes , Okatan Ilyas Ercan , Sezer Serdar , Keleşoğlu Dinçer Ayşe Bahar , Gülöksüz Aydemir Emine Gözde , Turgay Tahsin Murat , Kinikli Gülay , Ateş Aşkin
Published: July 2021

Objective

Behçet syndrome (BS) is a multisystemic chronic vasculitic disease. Among previous studies, although there are some that showed increased risk of subclinical atherosclerosis in BS, there are also others that showed the opposite. The objective of this study is to evaluate subclinical atherosclerosis in BS by using the cutoff value for intima-media thickness in the 2013 European Society of Cardiology/European Society of Hypertension guideline.

Methods

We conducted a cross-sectional analysis of 100 BS patients and 30 healthy volunteers at a single center in a 4-month period. All ultrasound scans were performed in a blind manner to the clinical assessment, and they were carried out by the same researcher by a B-mode ultrasonography.

Result

When we grouped the patients based on the presence of subclinical atherosclerosis, the frequency of subclinical atherosclerosis in the BS patients was found to be higher than that in the healthy controls (32% and 7%, respectively; p = 0.006). When a cutoff is used for carotid intima-media thickness, increased atherosclerosis risk is observed in BS patients with vascular involvement (p = 0.043).

Conclusions

Although higher inflammation and increased atherosclerosis in vascular BS patients were expected, this situation was not supported much in previous studies. We think that this may have been caused by mere comparison of numerical data, and usage of a cutoff value could be more significant in distinguishing what is normal and what is abnormal as in several medical parameters.
Rheumatology Training in Latin America
Authors: Fernández-Ávila Daniel G. , Patino-Hernandez Daniela , Kowalskii Sergio , Vargas-Caselles Alfredo , Sapag Ana Maria , Cachafeiro-Vilar Antonio , Meléndez Belia , Santiago-Pastelín Carlos , Graf Cesar , Rossetto Chayanne , Palleiro Daniel , Trincado Daniela , Fernández-Ávila Diana Carolina , Arrieta Dina , Reyes Gil , Baez Jossiel Then , Ugarte-Gil Manuel F. , Cardiel Mario , Colman Nelly , Chávez Nilmo , Burgos Paula I. , Montufar Ruben , Sandino Sayonara , Fuentes-Silva Yurilis , Soriano Enrique R.
Published: July 2021

Background/Objective

Demand for rheumatology care has steadily increased in recent years. The number of specialists in this field, however, seems insufficient. No recent studies have diagnosed the attributes of rheumatology training in Latin America.

Methods

This is a descriptive cross-sectional study. We obtained data on each country through local rheumatologists of the Pan-American League Against Rheumatism, who acted as principal investigators for participating countries. Our sample was analyzed and described through means and standard deviations or through frequencies and percentages, depending on the variable.

Results

Countries with the most rheumatology-training programs were Brazil (n = 50), Argentina (n = 18), and Mexico (n = 15). Ecuador, Honduras, and Nicaragua do not have rheumatology-training programs. The countries with the most available slots for rheumatology residents were Brazil (n = 126) and Argentina (n = 36). To be admitted into rheumatology training, candidates were required to have completed graduate studies in internal medicine in 42.1% of the programs. In 8 countries (42.1%), residents are not required to pay tuition; the median cost of tuition in the remaining countries is US $528 (interquartile range, US $2153).

Conclusions

Conditions associated with rheumatology training in Latin America vary. Significant differences exist in income and tuition fees for residents, for example, and 4 countries in Latin America do not currently offer programs. Information collected in this study will be useful when comparing the status of rheumatology services offered in Latin America with those in other countries. Most countries require a wider offering of rheumatology-training programs, as well as more available slots.
Clinical Characteristics and Outcomes of Patients With ANCA-Associated Vasculitides in a Colombian Hospital
Authors: Santacruz-Sandoval Evelyn , López-Bonilla Jorge , Guevara-Calderón Lizbeth A. , Nieto-Aristizábal Ivana , Ruiz-Ordoñez Ingrid , Cañas Carlos A. , Santos Víctor A. , Tobón Gabriel J. , Aguirre-Valencia David
Published: July 2021

Background/Objective

Antineutrophil cytoplasmic antibody–associated vasculitides (AAVs) are uncommon systemic autoimmune diseases, of which few reports exist in Latin America. Our aim was to examine AAV evaluated in a high-complexity hospital in southwestern Colombia, with emphasis in severe forms.

Methods

A medical records review study of 67 patients was performed, and data were collected from electronic registries. Moderate and severe AAVs were defined as the presence of life-threatening complications, unfavorable Birmingham Vasculitis Activity Score outcomes, and hospitalization requirements at the time of diagnosis and by the last follow-up, between 2011 and 2019. Clinical manifestations, treatment, and outcomes were evaluated. The AAV subtypes were compared.

Results

A total of 67 cases were included. The majority were female (n = 44, 65.67%), and the median age was 52 (40–64) years. Granulomatosis with polyangiitis (GPA) was the most frequent with 42 patients (62.68%), followed by microscopic polyangiitis (MPA) and eosinophilic GPA, with 15 patients (22.38%) and 10 patients (14.92%), respectively. Forty-four patients (65.67%) presented pulmonary symptoms. The highest Birmingham Vasculitis Activity Score corresponded to MPA, with 21 (12–25) points. Fifteen patients (22.4%) were admitted to the intensive care unit throughout the course of the disease, of whom 10 had GPA. The longest stay and duration of mechanical ventilation were seen in MPA. The principal treatments were corticosteroids and cyclophosphamide, and the main outcome was end-stage renal disease.

Conclusions

In this cohort of AAV, most of cases corresponded to GPA, and pulmonary manifestations were the most common. Microscopic polyangiitis was the more severe subtype as it showed worse impairment in clinical characteristics and intensive care unit requirements.
Community Mobility and COVID-19 Dynamics in Jakarta, Indonesia
Authors: Nanda Ratih Oktri , Nursetyo Aldilas Achmad , Ramadona Aditya Lia , Imron Muhammad Ali , Fuad Anis , Setyawan Althaf , Ahmad Riris Andono
Published: July 2021

Background

Human mobility could act as a vector to facilitate the spread of infectious diseases. In response to the COVID-19 pandemic, Google Community Mobility Reports (CMR) provide the necessary data to explore community mobility further. Therefore, we aimed to examine the relationship between community mobility on COVID-19 dynamics in Jakarta, Indonesia.

Methods

We utilized the mobility data from Google from February 15 to December 31, 2020. We explored several statistical models to estimate the COVID-19 dynamics in Jakarta. Model 1 was a Poisson Regression Generalized Linear Model (GLM), Model 2 was a Negative Binomial Regression Generalized Linear Model (GLM), and Model 3 was a Multiple Linear Regression (MLR).

Results

We found that Multiple Linear Regression (MLR) with some adjustments using Principal Component Analysis (PCA) was the best fit model. It explained 52% of COVID-19 cases in Jakarta (R-Square: 0.52, p<0.05). All mobility variables were significant predictors of COVID-19 cases (p<0.05). More precisely, about 1% change in grocery and pharmacy would contribute to a 4.12% increase of the COVID-19 cases in Jakarta. Retails and recreations, workplaces, transit stations, and parks would result in 3.11%, 2.56%, 2.26%, and 1.93% of more COVID-19 cases, respectively.

Conclusion

Our study indicates that increased mobility contributes to increased COVID-19 cases. This finding will be beneficial to assist policymakers to have better outbreak management strategies, to anticipate increased COVID-19 cases in the future at certain public places and during seasonal events such as annual religious holidays or other long holidays in particular.
Analysis of Blood Gene Expression Data Toward Early Detection of Alzheimer’s Disease
Authors: Gorji Hamed Taheri , Kardan Ramtin , Rezagholizadeh Neda
Published: July 2021

Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder and the most commonly diagnosed cause of dementia, and it is the fifth leading cause of death among people aged 65 and older. During the years, the early diagnosis of AD patients has been a significant concern for researchers, in view of the fact that early diagnosis not only can lead to saving lives of the AD patients but also could bring a considerable amount of saving in health and long-term care expenditures for both people and the government. Mild cognitive impairment (MCI), defined as a transitional state between being healthy and having AD, is considered an established risk factor for AD. Hence, an accurate and reliable diagnosis of MCI and, consequently, discrimination between healthy people, MCI individuals, and AD patients can play a crucial role in the early diagnosis of AD. In recent years, analysis of blood gene expression data has been grabbed more attention than the conventional AD diagnosis method because it provides the opportunity to investigate the biochemical pathways, cellular functions, and regulatory mechanisms for finding the key genes associated with MCI and AD. Therefore, in this study, we employed blood gene expression data from Alzheimer’s Disease Neuroimaging Initiative (ADNI), two feature selection methods for determining the most prominent genes related to MCI and AD, and three classifiers for the most accurate discrimination between three groups of healthy, MCI and AD. The proposed method yielded the selection of top ten genes from more than 49,000 genes and the best overall classification result between healthy and AD patients with average values of the area under the curve (AUC) of 0.77 ± 0.08. Furthermore, gene ontology (GO) analysis revealed that four genes were enriched with the GO terms of regulation of cell proliferation, negative regulation of cell population proliferation, signaling receptor binding, biological adhesion, and cytokine production.
Effect of dialysis modality on the survival of end-stage renal disease patients starting dialysis in Sabah from 2007 to 2017: a retrospective cohort study
Authors: Keowmani Thamron , Ghazali Anis Kausar , Yaacob Najib Majdi , Wong Koh Wei
Published: July 2021

Background

The effect of dialysis modality on the survival of end-stage renal disease patients is a major public health interest.

Methods

In this retrospective cohort study, all adult end-stage renal disease patients receiving dialysis treatment in Sabah between January 1, 2007 and December 31, 2017 as identified from the Malaysian Dialysis and Transplant Registry were evaluated and followed up through December 31, 2018. The endpoint was all-cause mortality. The observation time was defined as the time from the date of dialysis initiation after the onset of end-stage renal disease to whichever of the following that came first: date of death, date of transplantation, date of last follow-up, date of recovered kidney function, or December 31, 2018. Weighted Cox regression was used to estimate the effect of dialysis modality. Analyses were restricted to patients with complete data on all variables.

Results

1,837 patients began hemodialysis and 156 patients started with peritoneal dialysis, yielding 7,548.10 (potential median 5.48 years/person) and 747.98 (potential median 5.68 years/person) person-years of observation. 3.1% of patients were lost to follow-up. The median survival time was 5.8 years (95% confidence interval: 5.4, 6.3) among patients who started on hemodialysis and 7.0 years (95% confidence interval: 5.9, indeterminate) among those who started on peritoneal dialysis. The effect of dialysis modality was not significant after controlling for confounders. The average hazard ratio was 0.80 (95% confidence interval: 0.61, 1.05) with hemodialysis as a reference.

Conclusion

There was no evidence of a difference in mortality between hemodialysis and peritoneal dialysis.
The cost-effectiveness of accelerated partner therapy (APT) compared to standard contact tracing for people with chlamydia: an economic evaluation based on the LUSTRUM population-based chlamydia transmission model
Authors: Williams EV , Okeke Ogwulu CB , Estcourt CS , Howarth AR , Copas A , Low N , Althaus C , Mapp F , Woode Owusu M , Symonds M , Roberts TE
Published: July 2021

Objective

To investigate the cost-effectiveness of accelerated partner therapy (APT) compared with standard contact tracing for people with sexually transmitted chlamydia infection in the United Kingdom

Design

Economic evaluation using a model consisting of two components: a population-based chlamydia transmission component, to estimate the impact of APT on chlamydia prevalence, and an economic component, to estimate the impact of APT on healthcare costs and health outcomes.

Setting

United Kingdom

Participants

Hypothetical heterosexual population of 50,000 men and 50,000 women aged 16-34 years.

Main Outcome Measures

Cost-effectiveness based on quality-adjusted life years (QALYs) gained and major outcomes averted (MOA), defined as mild pelvic inflammatory disease (PID), severe PID, chronic pelvic pain, ectopic pregnancy, tubal factor infertility and epididymitis.

Results

For a model population of 50,000 men and 50,000 women and an APT intervention lasting 5 years, the intervention cost of APT (£135,201) is greater than the intervention cost of standard contact tracing (£116,334). When the costs of complications arising from chlamydia are considered, the total cost of APT (£370,657) is lower than standard contact tracing (£379,597). Thus, APT yields a total cost saving of approximately £9000 and leads to 73 fewer major outcomes and 21 fewer QALYs lost. Hence, APT is the dominant PN strategy. APT remained cost-effective across the full range of sensitivity analyses.

Conclusions

Based on cost-effectiveness grounds APT is likely to be recommended as an alternative to standard contact tracing for chlamydia infection in the United Kingdom
Potentially inappropriate prescribing of DOACs to people with mechanical heart valves: a federated analysis of 57.9 million patients’ primary care records in situ using OpenSAFELY
Authors:   The OpenSAFELY Collaborative, Fisher Louis , Speed Victoria , Curtis Helen J , Rentsch Christopher T , Wong Angel YS , Schultze Anna , Massey Jon , Inglesby Peter , Morton Caroline E , Wood Marion , Walker Alex J , Morley Jessica , Mehrkar Amir , Bacon Seb , Hickman George , Bates Chris , Croker Richard , Evans David , Ward Tom , Cockburn Jonathan , Davy Simon , Bhaskaran Krishnan , Smith Becky , Williamson Elizabeth , Hulme William , Green Amelia , Eggo Rosalind M , Forbes Harriet , Tazare John , Parry John , Hester Frank , Harper Sam , Meadows Jonathan , O’Hanlon Shaun , Eavis Alex , Jarvis Richard , Avramov Dima , Griffiths Paul , Fowles Aaron , Parkes Nasreen , Douglas Ian J , Evans Stephen JW , Tomlinson Laurie , MacKenna Brian , Smeeth Liam , Goldacre Ben
Published: July 2021

National guidance was issued during the COVID-19 pandemic to switch patients on warfarin to direct oral anticoagulants (DOACs) where appropriate as these require less frequent blood testing. DOACs are not recommended for patients with mechanical heart valves. We conducted a retrospective cohort study of DOAC prescribing in people with a record of a mechanical heart valve between September 2019 and May 2021, and describe the characteristics of this population. We identified 15,457 individuals with a mechanical heart valve recorded in their records, of whom 1058 (6.8%) had been prescribed a DOAC during the study period. 767 individuals with a record of a mechanical heart valve were currently prescribed a DOAC as of May 31st 2021. This is suggestive of inappropriate prescribing of DOACs in individuals with mechanical heart valves. Direct alerts have been issued to clinicians through their EHR software informing the issue. We show that the OpenSAFELY platform can be used for rapid audit and feedback to mitigate the indirect health impacts of COVID-19 on the NHS. We will monitor changes in prescribing for this risk group over the following months.
Identification of TAZ as the essential molecular switch in orchestrating SCLC phenotypic transition and metastasis
Authors: Jin Yujuan , Zhao Qiqi , Zhu Weikang , Feng Yan , Xiao Tian , Zhang Peng , Jiang Liyan , Hou Yingyong , Guo Chenchen , Huang Hsinyi , Chen Yabin , Tong Xinyuan , Cao Jiayu , Li Fei , Zhu Xueliang , Qin Jun , Gao Dong , Liu Xin-Yuan , Zhang Hua , Chen Luonan , Thomas Roman K , Wong Kwok-Kin , Wang Yong , Hu Liang , Ji Hongbin
Published: July 2021

Small cell lung cancer (SCLC) is a recalcitrant cancer featured with high metastasis. However, the exact cell type contributing to metastasis remains elusive. UsingRb1L/L/Trp53L/Lmouse model, we identify the NCAMhiCD44lo/−subpopulation as SCLC metastasizing cell (SMC), which is progressively transitioned from non-metastasizing NCAMloCD44hicell (Non-SMC). Integrative chromatin accessibility and gene expression profiling studies reveal an important role of SWI/SNF complex, and knockout of its central component,Brg1, significantly inhibits such phenotypic transition and metastasis. Mechanistically, TAZ is silenced by SWI/SNF complex during SCLC malignant progression, and its knockdown promotes SMC transition and metastasis. Importantly, ectopic TAZ expression reversely drives SMC-to-Non-SMC transition and alleviates metastasis. Single-cell RNA-sequencing analyses identify SMC as the dominant subpopulation in human SCLC metastasis, and immunostaining data show a positive correlation between TAZ and patient prognosis. These data uncover high SCLC plasticity and identify TAZ as key molecular switch in orchestrating SCLC phenotypic transition and metastasis.
European-wide forest monitoring substantiate the neccessity for a joint conservation strategy to rescue European ash species (Fraxinus spp.)
Authors: George Jan-Peter , Sanders Tanja GM , Timmermann Volkmar , Potočić Nenad , Lang Mait
Published: July 2021

European ash (Fraxinus excelsior) and narrow-leafed ash (F. angustifolia) are keystone forest tree species in Europe with a broad ecological amplitude and significant economic importance. Besides global warming both species are currently under significant thread by an invasive fungal pathogen that has been progressively spreading throughout the continent for almost three decades. Ash dieback caused by the invasive ascomyceteHymenoscyphus fraxineusis capable of damaging ash trees of all age classes and often leads to the ultimate death of a tree after years of progressively developing crown defoliation. While studies at national and regional level already suggested rapid decline of ash populations as a result of ash dieback, a comprehensive survey at European level with harmonized crown assessment data across countries could shed more light into the population decline from a pan-European perspective and could also pave the way for a new conservation strategy beyond national boarders. Here, we present data from the ICP Forests Level I crown condition monitoring including 27 countries, covering the timespan from 1987-2020. In total, 407 survey plots randomly distributed across these countries were analyzed resulting in >36,000 individual observations. We found a substantial increase in defoliation and mortality over time indicating that crown defoliation has almost doubled during the last three decades. Hotspots of mortality are currently situated in southern Scandinavia and north-eastern Europe, well corresponding to the fact that the disease spread fast from north-east to north-west. Overall survival probability after nearly 30 years of infection has already reached a critical value of 0.51, but with large differences among regions (0.00-0.907). Both a Cox proportional hazard model as well as an Aalen additive regression model strongly suggest that survival of ash is significantly lower in locations with excessive water regime and which experienced more extreme precipitation events during the last two decades. Our results underpin the neccessity for fast governmental acting and joint rescue efforts beyond national boarders since overall mean defoliation will likely reach 50% as early as 2030 as suggested by time series forecasting. We strongly recommend to develop a pan-European conservation strategy before the decline will reach its tipping point resulting into non-reversible loss of diversity in the European forest landscape.
CCD
2: design constructs for protein expression, the easy way
Authors: Murachelli Andrea Giovanni , Damaskos George , Perrakis Anastassis
Published: July 2021

Studying the function or structure of proteins usually requires the generation of many protein-truncation constructs for recombinant expression, which is a tedious and error-prone job. CCD
2 is a software tool designed to facilitate and automate this task. CCD
2 helps scientists by aggregating the information necessary to design protein-expression constructs. This information includes sequence conservation, secondary structure prediction, domain(s) and disorder detection, post-translational modifications and information on similar (domain) structures that are available in the Protein Data Bank. CCD
2 then allows users to easily choose the boundaries for protein constructs and automatically generates the primers necessary for construct amplification by polymerase chain reaction. Finally, CCD
2 provides a quick analysis of the properties of the chosen constructs, together with their DNA vector maps for bookkeeping. The features of CCD
2 are discussed step by step, showing that it can be a useful tool for laboratories that engage in recombinant protein production for any type of experiment, and in particular for structural biology studies.
Structure of the unique tetrameric STENOFOLIA homeodomain bound with target promoter DNA
Authors: Pathak Prabhat Kumar , Zhang Fei , Peng Shuxia , Niu Lifang , Chaturvedi Juhi , Elliott Justin , Xiang Yan , Tadege Million , Deng Junpeng
Published: July 2021

Homeobox transcription factors are key regulators of morphogenesis and development in both animals and plants. In plants, the WUSCHEL-related homeobox (WOX) family of transcription factors function as central organizers of several developmental programs ranging from embryo patterning to meristematic stem-cell maintenance through transcriptional activation and repression mechanisms. The Medicago truncatula
STENOFOLIA (STF) gene is a master regulator of leaf-blade lateral development. Here, the crystal structure of the homeodomain (HD) of STF (STF-HD) in complex with its promoter DNA is reported at 2.1 Å resolution. STF-HD binds DNA as a tetramer, enclosing nearly the entire bound DNA surface. The STF-HD tetramer is partially stabilized by docking of the C-terminal tail of one protomer onto a conserved hydrophobic surface on the head of another protomer in a head-to-tail manner. STF-HD specifically binds TGA motifs, although the promoter sequence also contains TAAT motifs. Helix α3 not only serves a canonical role as a base reader in the major groove, but also provides DNA binding in the minor groove through basic residues located at its C-terminus. The structural and functional data in planta reported here provide new insights into the DNA-binding mechanisms of plant-specific HDs from the WOX family of transcription factors.
Structural studies of complexes of kallikrein 4 with wild-type and mutated forms of the Kunitz-type inhibitor BbKI
Authors: Li Mi , Srp Jaroslav , Mareš Michael , Wlodawer Alexander , Gustchina Alla
Published: July 2021

Structures of BbKI, a recombinant Kunitz-type serine protease inhibitor fromBauhinia bauhinioides, complexed with human kallikrein 4 (KLK4) were determined at medium-to-high resolution in four crystal forms (space groupsP3121,P6522,P21andP61). Although the fold of the protein was virtually identical in all of the crystals, some significant differences were observed in the conformation of Arg64 of BbKI, the residue that occupies the S1 pocket in KLK4. Whereas this residue exhibited two orientations in the highest resolution structure (P3121), making either a canonical trypsin-like interaction with Asp189 of KLK4 or an alternate interaction, only a single alternate orientation was observed in the other three structures. A neighboring disulfide, Cys191–Cys220, was partially or fully broken in all KLK4 structures. Four variants of BbKI in which Arg64 was replaced by Met, Phe, Ala and Asp were expressed and crystallized, and their structures were determined in complex with KLK4. Structures of the Phe and Met variants complexed with bovine trypsin and of the Phe variant complexed with α-chymotrypsin were also determined. Although the inhibitory potency of these variant forms of BbKI was lowered by up to four orders of magnitude, only small changes were seen in the vicinity of the mutated residues. Therefore, a totality of subtle differences in KLK4–BbKI interactions within the fully extended interface in the structures of these variants might be responsible for the observed effect. Screening of the BbKI variants against a panel of serine proteases revealed an altered pattern of inhibitory specificity, which was shifted towards that of chymotrypsin-like proteases for the hydrophobic Phe and Met P1 substitutions. This work reports the first structures of plant Kunitz inhibitors with S1-family serine proteases other than trypsin, as well as new insights into the specificity of inhibition of medically relevant kallikreins.
Structure of a C1/C4-oxidizing AA9 lytic polysaccharide monooxygenase from the thermophilic fungus Malbranchea cinnamomea
Authors: Mazurkewich Scott , Seveso Andrea , Hüttner Silvia , Brändén Gisela , Larsbrink Johan
Published: July 2021

The thermophilic fungus Malbranchea cinnamomea contains a host of enzymes that enable its ability as an efficient degrader of plant biomass and that could be mined for industrial applications. This thermophilic fungus has been studied and found to encode eight lytic polysaccharide monooxygenases (LPMOs) from auxiliary activity family 9 (AA9), which collectively possess different substrate specificities for a range of plant cell-wall-related polysaccharides and oligosaccharides. To gain greater insight into the molecular determinants defining the different specificities, structural studies were pursued and the structure of McAA9F was determined. The enzyme contains the immunoglobulin-like fold typical of previously solved AA9 LPMO structures, but contains prominent differences in the loop regions found on the surface of the substrate-binding site. Most significantly, McAA9F has a broad substrate specificity, with activity on both crystalline and soluble polysaccharides. Moreover, it contains a small loop in a region where a large loop has been proposed to govern specificity towards oligosaccharides. The presence of the small loop leads to a considerably flatter and more open surface that is likely to enable the broad specificity of the enzyme. The enzyme contains a succinimide residue substitution, arising from intramolecular cyclization of Asp10, at a position where several homologous members contain an equivalent residue but cyclization has not previously been observed. This first structure of an AA9 LPMO from M. cinnamomea aids both the understanding of this family of enzymes and the exploration of the repertoire of industrially relevant lignocellulolytic enzymes from this fungus.
A GH13 α-glucosidase from Weissella cibaria uncommonly acts on short-chain maltooligosaccharides
Authors: Wangpaiboon Karan , Laohawuttichai Pasunee , Kim Sun-Yong , Mori Tomoyuki , Nakapong Santhana , Pichyangkura Rath , Pongsawasdi Piamsook , Hakoshima Toshio , Krusong Kuakarun
Published: July 2021

α-Glucosidase (EC 3.2.1.20) is a carbohydrate-hydrolyzing enzyme which generally cleaves α-1,4-glycosidic bonds of oligosaccharides and starch from the nonreducing ends. In this study, the novel α-glucosidase from Weissella cibaria BBK-1 (WcAG) was biochemically and structurally characterized. WcAG belongs to glycoside hydrolase family 13 (GH13) and to the neopullanase subfamily. It exhibits distinct hydrolytic activity towards the α-1,4 linkages of short-chain oligosaccharides from the reducing end. The enzyme prefers to hydrolyse maltotriose and acarbose, while it cannot hydrolyse cyclic oligosaccharides and polysaccharides. In addition, WcAG can cleave pullulan hydrolysates and strongly exhibits transglycosylation activity in the presence of maltose. Size-exclusion chromatography and X-ray crystal structures revealed that WcAG forms a homodimer in which the N-terminal domain of one monomer is orientated in proximity to the catalytic domain of another, creating the substrate-binding groove. Crystal structures of WcAG in complexes with maltose, maltotriose and acarbose revealed a remarkable enzyme active site with accessible +2, +1 and −1 subsites, along with an Arg–Glu gate (Arg176–Glu296) in front of the active site. The −2 and −3 subsites were blocked by Met119 and Asn120 from the N-terminal domain of a different subunit, resulting in an extremely restricted substrate preference.
Mycobacterium tuberculosis ferritin: a suitable workhorse protein for cryo-EM development
Authors: Gijsbers Abril , Zhang Yue , Gao Ye , Peters Peter J. , Ravelli Raimond B. G.
Published: July 2021

The use of cryo-EM continues to expand worldwide and calls for good-quality standard proteins with simple protocols for their production. Here, a straightforward expression and purification protocol is presented that provides an apoferritin, bacterioferritin B (BfrB), from Mycobacterium tuberculosis with high yield and purity. A 2.12 Å resolution cryo-EM structure of BfrB is reported, showing the typical cage-like oligomer constituting of 24 monomers related by 432 symmetry. However, it also contains a unique C-terminal extension (164–181), which loops into the cage region of the shell and provides extra stability to the protein. Part of this region was ambiguous in previous crystal structures but could be built within the cryo-EM map. These findings and this protocol could serve the growing cryo-EM community in characterizing and pushing the limits of their electron microscopes and workflows.
Gender-based implications of the COVID-19 pandemic on household diet diversity and nutritional security in Pakistan
Authors: Shahbaz Pomi , Haq Shamsheer ul , Khalid Umer Bin , Boz Ismet
Published: July 2021

Purpose

The COVID-19 pandemic has profound implications on the food and nutritional security of millions of households. The study assessed the impacts of the COVID-19 pandemic on diet diversity, calorie consumption and intake of essential nutrients based on the gender of the households.

Design/methodology/approach

Mixed-design ANOVA and logistic regression were used to analyze the collected data from 260 female- and 463 male-headed households through an online survey in Pakistan.

Findings

The outcomes revealed that the diet diversity of female households was affected more due to the COVID-19 compared to male households. The decline in daily nutrients' (protein, phosphorus, zinc, iron and iodine) intake during the COVID-19 was also greater for female-headed households than male-headed households. The share of all food groups in daily calorie and nutrient provision decreased significantly during the COVID-19 for both types of households. The share of meat and meat products declined more for female-headed households compared to male-headed households. The share of perishable commodities in calorie provision to female and male households decreased 2% during the COVID-19 compared to the normal period. Small- and medium-sized female and male households were less likely to experience worsened diet diversity than large-sized households during the COVID-19. Low-income compared to medium- and high-income female and male households were more likely to report declined food diversity during the COVID-19.

Research limitations/implications

The data used in this study were collected through an online survey due to public health measures imposed in the country.

Originality/value

Despite the emergence of literature on the implications of the pandemic on food security, the studies related to the gender-based impacts of COVID-19 on diet diversity and nutritional intakes of necessary nutrients are still non-existent. The current study will add to the literature by filling this gap.