bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction Between Primary Tumor Resection, Primary Tumor Location, and Survival in Synchronous Metastatic Colorectal Cancer
Authors: van der Kruijssen Dave E.W. , Brouwer Nelleke P.M. , van der Kuil Auke J.S. , Verhoeven Rob H.A. , Elias Sjoerd G. , Vink Geraldine R. , Punt Cornelis J.A. , de Wilt Johannes H.W. , Koopman Miriam
Published: April 2021

Objectives:

Location of the primary tumor has prognostic value and predicts the effect of certain therapeutics in synchronous metastatic colorectal cancer. We investigated whether the association between primary tumor resection (PTR) and overall survival (OS) also depends on tumor location.

Methods:

Data on synchronous metastatic colorectal cancer patients from the Netherlands Cancer Registry (n=16,106) and Surveillance, Epidemiology, and End Results (SEER) registry (n=19,584) were extracted. Cox models using time-varying covariates were implemented. Median OS for right-sided colon cancer (RCC), left-sided colon cancer, and rectal cancer was calculated using inverse probability weighting and a landmark point of 6 months after diagnosis as reference.

Results:

The association between PTR and OS was dependent on tumor location (P<0.05), with a higher median OS of upfront PTR versus upfront systemic therapy in Netherlands Cancer Registry (NCR) of 1.9 (95% confidence interval: 0.9-2.8), 4.3 (3.3-5.6), and 3.4 (0.6-7.6) months in RCC, left-sided colon cancer and rectal cancer, respectively. In SEER data, the difference was 6.0 (4.0-8.0), 8.0 (5.0-10.0), and 10.0 (7.0-13.0) months, respectively. Hazard plots indicate a higher hazard of death 2 to 3 months after PTR in RCC.

Conclusion:

Upfront PTR is associated with improved survival regardless of primary tumor location. Patients with RCC appear to have less benefit because of higher mortality during 2 to 3 months after PTR.
Generalized Multinucleate Cell Angiohistiocytoma: Histopathological and Immunohistochemical Analyses of 10 Lesions
Authors: Ross Casey L. , Chung Jina , Ross Nicholas A. , Lee Jason B.
Published: April 2021

Multinucleate cell angiohistiocytoma (MCAH) is an uncommon fibrohistiocytic disorder that usually presents as a localized solitary papule or multiple grouped papules. Generalized presentation is very rare with less than 20 cases reported in the literature. In this article, we present histopathological and immunohistochemical studies of 10 lesions from a patient with generalized MCAH. In all lesions, the histopathological changes were confined to a discrete zone of the superficial dermis that consisted of (1) an increase in the number of capillary-sized vessels with thickened walls, (2) presence of oval to dendritic spindle cells and stellate hyperchromatic multinucleated cells, (3) fibrosis marked by compact collagen, (4) hypertrophy and hyperplasia of small nerve fibers, and (5) a moderately dense lymphocytic infiltrate. The entire population of the cellular component including the multinucleated cells stained for CD10, whereas a subpopulation of the mononuclear spindle cells stained for factor XIIIa and CD68. CD34 highlighted only the blood vessels. The results confirm that the multinucleated cells lack expression of CD68 and factor XIIIa and that CD10 may be used to highlight the entire cellular component. The rarely reported hypertrophy and hyperplasia of nerve fibers in MCAH may be a common finding as it was observed in all 10 lesions.
Visual Field Endpoints Based on Subgroups of Points May Be Useful in Glaucoma Clinical Trials: A Study With the Humphrey Field Analyzer and Compass Perimeter
Authors: Barkana Yaniv , Leshno Ari , Stern Ori , Singer Reut , Russ Hermann , Oddone Francesco , Lanzetta Paolo , Perdicchi Andrea , Johnson Chris A. , Garway-Heath David F. , Rossetti Luca M. , Skaat Alon
Published: April 2021

Precis:

Visual field (VF) endpoints based on average deviation of specific subsets of points rather than all points may offer a more homogeneous data set without necessarily worsening test-retest variability and so may be useful in clinical trials.

Purpose:

The purpose of this study was to characterize the outcome measures encompassing particular subsets of VF points and compare them as obtained with Humphrey [Humphrey visual field analyser (HVF)] and Compass perimeters.

Methods:

Thirty patients with imaging-based glaucomatous neuropathy performed a pair of 24-2 tests with each of 2 perimeters. Nonweighted mean deviation (MD) was calculated for the whole field and separate vertical hemifields, and again after censoring of points with low sensitivity (MDc) and subsequently including only “abnormal” points with a total deviation probability of <5% (MDc5%) or <2% (MDc2%). Test-retest variability was assessed using Bland-Altman 95% limits of agreement (95%LoA).

Results:

For the whole field, using HVF, MD was −7.5±6.9 dB, MDc −3.6±2.8 dB, MDc5% −6.4±1.7 dB, and MDc2% −7.3±1.5 dB. With Compass the MD was −7.5±6.6, MDc −2.9±1.7 dB, MDc5% −6.3±1.5, and MDC2% −7.9±1.6. The respective 95%LoA were 5.5, 5.3, 4.6, and 5.6 with HVF, and 4.8, 3.7, 7.1, and 7.1 with Compass. The respective number of eligible points were 52, 42±12, 20±11, and 15±9 with HVF, and 52, 41.2±12.6, 10±7, and 7±5 with Compass. With both machines, SD and 95%LoA increased in hemifields compared with the total field, but this increase was mitigated after censoring.

Conclusion:

Restricting analysis to particular subsets of points of interest in the VF after censoring points with low sensitivity, as compared with using the familiar total field MD, can provide outcome measures with a broader range of MD, a markedly reduced SD and therefore more homogeneous data set, without necessarily worsening test-retest variability.
Evaluation of an e-Learning Breastfeeding Program for Postpartum Mothers of Moderately High-Risk Newborn Infants Admitted to the Special Care Nursery
Authors: Fu Mei-Ling , Lee Tzu-Ying , Kuo Su-Chen
Published: April 2021

Because of a lack of proper breastfeeding education to mothers and the visitation policy in the special care nursery, breastfeeding initiation and maintenance can be very challenging for both the mother and her infant who is admitted to the neonatal special care nursery after birth. Difficulties associated with forming initial bonds may contribute to some mothers changing their mind about their initially chosen feeding method. The aim of this quasi-experimental study was to evaluate the effectiveness of an e-learning breastfeeding program on maternal breastfeeding outcomes. Thirty-four mothers in the comparison group received routine care; 34 in the intervention group received an e-learning breastfeeding program and routine care. The program included 28 modules of different topics downloaded to a personal tablet computer. Each module elaborated on a breastfeeding issue and provided video clips to show practice steps. During the mothers' 3- to 5-day stay in the postpartum unit, they could repeatedly watch selected topics related to their situations at their own pace. After adjusting for each infant's birth weight, mothers in the intervention group had better attachment to their infants, greater perceived nurse support, and a higher exclusive breastfeeding rate than mothers in the comparison group. Using a tablet computer device to disseminate breastfeeding education is a feasible and supplemental method for postpartum mothers whose infants are in the special care nursery. Through the demonstrated situations, mothers are better prepared to understand their high-risk infants and the situations they may encounter during breastfeeding.
Breastfeeding Plan of Care for the Late Preterm Infant From Birth Through Discharge
Authors: Busch Deborah W. , Silbert-Flagg JoAnne
Published: April 2021

The focus of this clinical practice case is on the initiation of successful breastfeeding in the late preterm infant. The exploration of a case of a late preterm infant born at 360/7 weeks' gestation, delivered via cesarean section, at risk for breastfeeding challenges. Common difficulties encountered in the late preterm, defined as 340/7 to 366/7 weeksʼ gestation, include delayed lactogenesis, decreased milk transfer, and ineffective suck and swallow. This may lead to hospital readmission due to inadequate weight gain, dehydration, and/or hyperbilirubinemia. These difficulties often result in premature breastfeeding cessation. A management strategy incorporating an individualized mother's breastfeeding plan of care across 2 care continuums is a unique feature in this case presentation. Assessment of the mother-infant dyad provides the foundation to develop clinical strategies to initiate prompt individualized lactation support for the late preterm infant. Interventions focus on establishing maternal milk supply, facilitating milk transfer, and providing breast milk to the newborn. This case illustrates how developing an individualized in-hospital breastfeeding plan for the late preterm infant, followed by comprehensive primary care follow-up at discharge, can reduce the risk factors that lead to readmission in the late preterm birth and promote breastfeeding success.
Diaphragm function in acute respiratory failure and the potential role of phrenic nerve stimulation
Authors: Reardon Peter M. , Wong Jenna , Fitzpatrick Aisling , Goligher Ewan C.
Published: April 2021

Purpose of review

The aim of this review was to describe the risk factors for developing diaphragm dysfunction, discuss the monitoring techniques for diaphragm activity and function, and introduce potential strategies to incorporate diaphragm protection into conventional lung-protective mechanical ventilation strategies.

Recent findings

It is increasingly apparent that an approach that addresses diaphragm-protective ventilations goals is needed to optimize ventilator management and improve patient outcomes. Ventilator-induced diaphragm dysfunction (VIDD) is common and is associated with increased ICU length of stay, prolonged weaning and increased mortality. Over-assistance, under-assistance and patient-ventilator dyssynchrony may have important downstream clinical consequences related to VIDD. Numerous monitoring techniques are available to assess diaphragm function, including respiratory system pressures, oesophageal manometry, diaphragm ultrasound and electromyography. Novel techniques including phrenic nerve stimulation may facilitate the achievement of lung and diaphragm-protective goals for mechanical ventilation.

Diaphragm protection is an important consideration in optimizing ventilator management in patients with acute respiratory failure. The delicate balance between lung and diaphragm-protective goals is challenging. Phrenic nerve stimulation may be uniquely situated to achieve and balance these two commonly conflicting goals.
Latinx Family Perspectives on Social Needs Screening and Referral during Well-Child Visits
Authors: Spain Angeline K. , Monahan Emma K. , Alvarez Kiara , Finno-Velasquez Megan
Published: April 2021

Objective:

To understand Latinx parent perspectives on screening and referral approaches to identify social determinants of health and address social and material needs during well-child visits and to identify techniques that promote their engagement with these approaches.

Study Design:

We investigated parent perspectives and engagement with social needs screening and referral practices during well-child visits using focus group methodology.

Results:

We conducted 17 focus groups (n = 134 parents and other primary caregivers) with families receiving care at sites operated by eight pediatric primary care clinics. Adding social needs screening and referral shifted the social context of well-child visits for Latinx parents. Participants reported greater engagement with the practices where they perceived an emotional connection with nurses and other clinicians and cultural brokering to ensure their screening responses accurately reflected family needs and priorities. Participants highlighted the importance of having a personal patient–provider relationship as many preferred to discuss social needs outside of the exam room.

Clinical Implications:

Nurses and other clinicians play a critical role in establishing systems needed to systematically screen and refer families for social needs. Future policy development should consider implications for nursing practice and leadership in adopting these approaches.
A Pediatric Nursing Professional Development Team’s COVID-19 Response
Authors: Bleazard Mark , Baker Ann-Marie C. , Crumpler Cherie L. , Dwyer Erin C. , Garver Dana , Gossman John W. , Haut Catherine M. , Jenkins Pamela S. , Lietzke Lisa M. , Nusspickel Kevin J. , Watson Norine
Published: April 2021

The role of pediatric hospitals in the COVID-19 pandemic changed quickly. The team of clinical nurse specialists and clinical nurse educators in a large pediatric hospital were instrumental in the institutional response through simulations, serving as change agents, collaboration, and implementing systems thinking. Leveraging the expertise of this team during this historical and unprecedented time optimized patient and associate safety as part of a pediatric hospital’s COVID-19 response.
Super-resolution structured illumination microscopy: past, present and future
Authors: Prakash Kirti , Diederich Benedict , Reichelt Stefanie , Heintzmann Rainer , Schermelleh Lothar
Published: April 2021

Structured illumination microscopy (SIM) has emerged as an essential technique for three-dimensional (3D) and live-cell super-resolution imaging. However, to date, there has not been a dedicated workshop or journal issue covering the various aspects of SIM, from bespoke hardware and software development and the use of commercial instruments to biological applications. This special issue aims to recap recent developments as well as outline future trends. In addition to SIM, we cover related topics such as complementary super-resolution microscopy techniques, computational imaging, visualization and image processing methods.

This article is part of the Theo Murphy meeting issue ‘Super-resolution structured illumination microscopy (part 1)’.
Extended mechanical force measurements using structured illumination microscopy
Authors: Korobchevskaya Kseniya , Colin-York Huw , Barbieri Liliana , Fritzsche Marco
Published: April 2021

Quantifying cell generated mechanical forces is key to furthering our understanding of mechanobiology. Traction force microscopy (TFM) is one of the most broadly applied force probing technologies, but its sensitivity is strictly dependent on the spatio-temporal resolution of the underlying imaging system. In previous works, it was demonstrated that increased sampling densities of cell derived forces permitted by super-resolution fluorescence imaging enhanced the sensitivity of the TFM method. However, these recent advances to TFM based on super-resolution techniques were limited to slow acquisition speeds and high illumination powers. Here, we present three novel TFM approaches that, in combination with total internal reflection, structured illumination microscopy and astigmatism, improve the spatial and temporal performance in either two-dimensional or three-dimensional mechanical force quantification, while maintaining low illumination powers. These three techniques can be straightforwardly implemented on a single optical set-up offering a powerful platform to provide new insights into the physiological force generation in a wide range of biological studies.

This article is part of the Theo Murphy meeting issue ‘Super-resolution structured illumination microscopy (part 1)'.
Attenuated alpha oscillations as an index of cortical hyperexcitability: Evidence from migraine patients
Authors: Fong Chun Yuen , Law Wai Him Crystal , Fahrenfort Johannes Jacobus , Braithwaite Jason J. , Mazaheri Ali
Published: April 2021

Anomalous phantom visual perceptions coupled to an aversion to some visual patterns has been associated with aberrant cortical hyperexcitability in migraine patients. Previous literature has found fluctuations of alpha oscillation (8-14 Hz) over the visual cortex to be associated with the gating of the visual stream. In the current study, we examined whether alpha activity was differentially modulated in migraineurs in anticipation of an upcoming stimulus as well as post-stimulus periods. We used EEG to examine the brain activity in a group of 28 migraineurs (17 with aura/11 without) and 29 non-migraineurs and compared the modulations of alpha power in the pre/post-stimulus period relative to onset of stripped gratings of 3 spatial frequencies 0.5, 3, and 13 cycles per degree (cpd). Overall, we found that that migraineurs had significantly less alpha power prior to the onset of the stimulus relative to controls. Moreover, relative to the control group, migraineurs had significantly greater post-stimulus alpha suppression (i.e event-related desynchronization) induced by the 3 cpd grating at the 2nd half of the experiment, the stimulus most often reported to induce visual disturbances. These findings taken together provide strong support of the presence of elevated cortical excitability in the visual cortex of migraine sufferers. We speculate that cortical hyperexcitation could be the consequence of impaired perceptual learning driven by the dysfunction of GABAergic inhibitory mechanism.
Predicting a diagnosis of ankylosing spondylitis using primary care health records – a machine learning approach
Authors: Kennedy Jonathan , Kennedy Natasha , Cooksey Roxanne , Choy Ernest , Siebert Stefan , Rahman Muhammad , Brophy Sinead
Published: April 2021

Ankylosing spondylitis is the second most common cause of inflammatory arthritis. However, a successful diagnosis can take a decade to confirm from symptom onset (via x-rays). The aim of this study was to use machine learning methods to develop a profile of the characteristics of people who are likely to be given a diagnosis of AS in future.

The Secure Anonymised Information Linkage databank was used. Patients with ankylosing spondylitis were identified using their routine data and matched with controls who had no record of a diagnosis of ankylosing spondylitis or axial spondyloarthritis. Data was analysed separately for men and women. The model was developed using feature/variable selection and principal component analysis to develop decision trees. The decision tree with the highest average F value was selected and validated with a test dataset.

The model for men indicated that lower back pain, uveitis, and NSAID use under age 20 is associated with AS development. The model for women showed an older age of symptom presentation compared to men with back pain and multiple pain relief medications. The models showed good prediction (positive predictive value 70%-80%) in test data but in the general population where prevalence is very low (0.09% of the population in this dataset) the positive predictive value would be very low (0.33%-0.25%).

Machine learning can be used to help profile and understand the characteristics of people who will develop AS, and in test datasets with artificially high prevalence, will perform well. However, when applied to a general population with low prevalence rates, such as that in primary care, the positive predictive value for even the best model would be 1.4%. Multiple models may be needed to narrow down the population over time to improve the predictive value and therefore reduce the time to diagnosis of ankylosing spondylitis.
COVID-19 Vaccine Hesitancy among the Adult Population in Bangladesh: A Nationally Representative Cross-sectional Survey
Authors: Hossain Mohammad Bellal , Alam Md. Zakiul , Islam Md. Syful , Sultan Shafayat , Faysal Md. Mahir , Rima Sharmin , Hossain Md. Anwer , Mamun Abdullah Al
Published: April 2021

Introduction

The study related to the COVID-19 vaccine hesitancy is scanty in the context of Bangladesh, despite the growing necessity of understanding the mass people’s vaccination-related behavior. Thus, the present study was conducted to assess the prevalence of the COVID-19 vaccine hesitancy and its associated factors in Bangladesh to fill the knowledge gap.

Methodology

This study adopted a cross-sectional study design to collect data from 1497 respondents using online (Google forms) and face-to-face interviews. We employed descriptive statistics and multiple hierarchical linear regression analysis.

Findings

The prevalence of vaccine hesitancy was 41.1%. Men had less hesitancy (β = -0.046, p = 0.030) than women. The Muslims (β = 0.057, p = 0.009) and the respondents living in the city corporation areas (β = 0.132, p <0.001) had more hesitancy. There was significant variation in vaccine hesitancy by administrative divisions (geographic regions). The vaccine hesitancy tended to decrease with increasing knowledge about the vaccine (β = -0.072, p=0.001) and the vaccination process (β= -0.058, p = 0.018). On the other hand, hesitancy increased with the increased negative attitudes towards vaccine (β = 0.291, p <0.001) and conspiracy beliefs towards the COVID-19 vaccine (β = 0.105, p=0.004). The perceived severity of the COVID-19 (β = -0.079, p=0.002) and perceived benefits of COVID-19 vaccination (β = -0.180, p=0.001) were negatively associated with hesitancy, while perceived barriers (β = 0.180, p <0.001) were positively associated. The participants were more hesitant to accept the vaccine from a specific manufacturer.

Conclusion

This study emphasizes that negative attitudes and conspiracies towards the COVID-19 vaccine should be reduced through effective communications and contracting with additional vaccine manufacturers should be prioritized. The barriers like online registration for receiving the COVID-19 vaccination need to be removed, and initiatives like text message service using the mobile phone operator can be introduced.

Highlights

About 41% of the respondents had had hesitancy to accept the COVID-19 vaccine.

The hesitancy increased with negative attitudes about vaccines and conspiracy beliefs.

Perceived barriers to receive the vaccine were increasing vaccine hesitancy.

Perceived severity of the COVID-19 decreased the vaccine hesitancy.

Perceived benefits of receiving the COVID-19 vaccine decreased the vaccine hesitancy.
Transmission of SARS-CoV-2 within households: a prospective cohort study in the Netherlands and Belgium – Interim results
Authors: Verberk JDM , de Hoog MLA , Westerhof I , Van Goethem S , Lammens C , Ieven M , de Bruin E , Bielicki J , Coenen S , van Beek J , Bonten M , Goossens H , Bruijning-Verhagen PCJL
Published: April 2021

Background

Household transmission studies are useful to obtain granular data on SARS-CoV-2 transmission dynamics and to gain insight into the main determinants. In this interim report we investigated secondary attack rates (SAR) by household and subject characteristics in the Netherlands and Belgium.

Methods

Households with a real-time reverse transcription polymerase chain reaction (RT-PCR) confirmed SARS-CoV-2 index case were enrolled <48 hours following report of the positive test result. Daily symptom follow-up, standardized nose-throat sampling at enrollment and at new-onset acute respiratory illness (ARI) and paired dried blood spots (DBS) were collected from each participant. Children 0-2 years of age were additionally requested to collect a stool sample 7 days after enrollment and at new-onset of ARI. Swabs and stool samples were tested by RT-PCR for virus detection and DBS by multiplex protein microarray for detection of SARS-CoV-2 antibodies. The SAR was calculated 1) per-household as the proportion of households with ≥1 secondary SARS-CoV-2 case and 2) per-person as the probability of infection in household members at risk. We explored differences in SARs by household and subject characteristics.

Results

This analysis includes 117 households that completed follow-up between April-December 2020. Among 382 subjects, 74 secondary infections were detected, of which 13 (17.6%) were asymptomatic and 20 (27.0%) infections were detected by seroconversion only. Of cases detected by RT-PCR, 50 (67.6%) were found at enrollment. The household SAR was 44.4% (95%-CI: 35.4-53.9%) and was higher for index cases meeting the ARI case definition (52.3%; 95%-CI 41.4-62.9%) compared to mildly symptomatic (22.2%; 95%-CI: 9.4-42.7%) and asymptomatic index cases (0.0%; 95%-CI: 0.0-80.2%). The per-person SAR was 27.9% (95%-CI: 22.7-33.8%). Transmission was lowest from child to parent (9.1%; 95%-CI: 2.4-25.5%) and highest from parent to child (28.1%; 95%-CI: 19.7-38.4%) and in children 6-12 years (34.2%; 95%-CI: 20.1-51.4%). Among 141 subjects with RT-PCR confirmed SARS-CoV-2 infections, seroconversion was detected in 111 (78.7%).

Conclusion

We found a high household SAR, with the large majority of transmissions detected early after identification of the index case. Our findings confirm differential SAR by symptom status of the index. In almost a quarter of RT-PCR positive cases, no antibodies were detected. Other factors influencing transmission will be further explored as more data accumulate.
Exploring the Behavioral Determinants of COVID-19 Vaccine Acceptance among an Urban Population in Bangladesh: Implications for Behavior Change Interventions
Authors: Kalam Md Abul , Davis Thomas P. , Shano Shahanaj , Uddin Nasir , Islam Md. Ariful , Kanwagi Robert , Islam Ariful , Hassan Mohammad Mahmudul , Larson Heidi J.
Published: April 2021

Background

While vaccines ensure individual protection against COVID-19 infection, delay in receipt or refusal of vaccines will have both individual and community impacts. The behavioral factors of vaccine hesitancy or refusal are a crucial dimension that need understanding to implicate appropriate interventions. The aim of this study was to assess the behavioral determinants of COVID-19 vaccine acceptance and to provide recommendations to increase the uptake of COVID-19 vaccines in Bangladesh.

Methods

We employed a Barrier Analysis (BA) approach to examine twelve potential behavioral determinants (drawn from the Health Belief Model and Theory of Reasoned Action [TRA]) of intended vaccine acceptance. We conducted 45 interviews with those who intended to take the vaccine (Acceptors) and another 45 interviews with those who did not have that intention (Non-acceptors). We performed data analysis to find statistically significant differences and to identify which beliefs were most highly associated with acceptance and non-acceptance with COVID-19 vaccines.

Results

COVID-19 vaccine Acceptors in Dhaka were different from Non-acceptors in terms of many of their beliefs and responses. The behavioral determinants associated with the behavior included perceived social norms, perceived safety of COVID-19 vaccines and trust in them, perceived risk/susceptibility, perceived self-efficacy, perceived positive and negative consequences, perceived action efficacy, perceived severity of COVID-19, access, and perceived divine will. In line with the Health Belief Model, beliefs about the disease itself were highly correlated with vaccine acceptance, although not the only determinant. Other responses of Acceptors provide clues such as providing vaccination through government health facilities, schools, and kiosks, and having vaccinators maintain proper COVID-19 health and safety protocols as to ways to make it easier to boost acceptance.

Conclusion

An effective behavior change strategy for COVID-19 vaccines uptake will need to address multiple beliefs and behavioral determinants, reducing barriers and leveraging enablers identified in this study. The national plans on COVID-19 vaccination should adopt culturally and community label acceptable and appropriate evidence-based behavior change interventions strategies to promote high vaccination coverage and acceptance in all societal structures across the country.
Reopen or redistribute? - Modeling years of life lost due to Covid-19, socioeconomic status, and non-pharmaceutical interventions
Authors: John Jari
Published: April 2021

Research in the current pandemic has put a sharp focus on the health burden of Covid-19, thereby largely neglecting the cost to life from the socioeconomic consequences of its containment. The paper develops a model for assessing their proportionality. It compares the years of life lost (YLL) due to Covid-19 and the socioeconomic consequences of its containment. The model reconciles the normative life table approach with de facto socioeconomic realities by correcting YLL estimates for socioeconomic differences in life expectancy. It thereby aims to improve on the attribution of YLL due to immediate and fundamental sources of inequalities in life expectancy. The application of the approach to the pandemic suggests that the socioeconomic consequences of containment measures potentially come with a much higher life tag than the disease itself and therefore need urgent attention, especially in poorer and more unequal societies. Avoiding 3 million additional cases of extreme poverty may come with a similar life tag as protecting 1 million people from dying from Covid-19.
Effects of the COVID-19 Pandemic on Park Use in U.S. Cities
Authors: Jay Jonathan , Heykoop Felicia , Hwang Linda , de Jong Jorrit , Kondo Michelle
Published: April 2021

Introduction

The COVID-19 pandemic focused attention on city parks as important public resources. However, it is unknown how city park use in 2020 compared to prior years and whether COVID-19 may have exacerbated racial/ethnic inequities in access. Moreover, traditional methods of measuring park use present major drawbacks.

Methods

We analyzed monthly mobility data derived from a large panel of smartphone devices, cross-referenced with a database of parks locations sourced from local agencies. We assessed park use trends in 44 of the 50 most populous U.S. cities from January 2018 to November 2020 using interrupted time series regressions. We also compared parks to other city amenities (e.g., gyms and libraries).

Results

Based on a sample of 5,559 city parks, park visits declined by 14.6% (95% CI [9.2, 19.7], p < 0.001) from March through November 2020, compared to prior levels and trends. When we segmented the COVID-19 period by time of widespread closures (March-April) and partial-to-full reopenings (May-November), we estimated a larger reduction during closures (35.7% reduction, 95% CI [33.5, 37.8], p < 0.001) compared to the reduction during reopenings (8.0% reduction, 95% CI [1.9, 13.7], p = 0.001). Reductions for other amenities were more prolonged. In park service areas where a greater proportion of residents were White, reopening was associated with more visits, suggesting that racial privilege influenced access.

Conclusions

Smartphone mobility data can address a data availability gap for monitoring park use. Park use only declined modestly in 2020. Opportunities exist to make access more racially equitable.

Significance statement

Parks are public resources that promote health. Little is known about how parks have been used during the COVID-19 pandemic, when parks have become particularly important public spaces. This study introduces an approach to monitor park use over time, using location data from smartphones. This approach enabled the authors to evaluate trends in park use during the pandemic, including major gaps in visits to parks according to whether they mostly served White residents or residents of color. This big data approach offers advantages over traditional methods for monitoring park use and can help city officials to identify and address inequities in park access.
Adherence to minimal experimental requirements for defining extracellular vesicles and their functions: a systematic review
Authors: Poupardin Rodolphe , Wolf Martin , Strunk Dirk
Published: April 2021

Rigorous measures are required to cope with the advance of extracellular vesicle (EV) research, from 183 to 2,309 studies/year, between 2012-2020. The ‘MISEV’ guidelines requested standardizing methods, thereby assuring and improving of EV research quality. We investigated how EV research improved over time.

We conducted a keyword search in 5,093 accessible publications over the period 2012-2020 and analyzed the methodology used for EV isolation and characterization. We found a significant improvement over the years particularly regarding EV characterization where recent papers used a higher number of methods and EV markers to check for quantity and purity. Interestingly, we also found that EV papers using more methods and EV markers were cited more frequently cited. Papers citing MISEV criteria were more prone to use a higher number of characterization methods.

We therefore established a concise checklist summarizing MISEV criteria to support EV researchers towards reaching the highest standards in the field.

Abstract Figure

Graphical abstract
Causal neural mechanisms of context-based object recognition
Authors: Wischnewski Miles , Peelen Marius V.
Published: April 2021

Objects can be recognized based on their intrinsic features, including shape, color, and texture. In daily life, however, such features are often not clearly visible, for example when objects appear in the periphery, in clutter, or at a distance. Interestingly, object recognition can still be highly accurate under these conditions when objects are seen within their typical scene context. What are the neural mechanisms of context-based object recognition? According to parallel processing accounts, context-based object recognition is supported by the parallel processing of object and scene information in separate pathways. Output of these pathways is then combined in downstream regions, leading to contextual benefits in object recognition. Alternatively, according to feedback accounts, context-based object recognition is supported by (direct or indirect) feedback from scene-selective to object-selective regions. Here, in three pre-registered transcranial magnetic stimulation (TMS) experiments, we tested a key prediction of the feedback hypothesis: that scene-selective cortex causally and selectively supports context-based object recognition before object-selective cortex does. Early visual cortex (EVC), object-selective lateral occipital cortex (LOC), and scene-selective occipital place area (OPA) were stimulated at three time points relative to stimulus onset while participants categorized degraded objects in scenes and intact objects in isolation, in different trials. Results confirmed our predictions: relative to isolated object recognition, context-based object recognition was selectively and causally supported by OPA at 160-200 ms after onset, followed by LOC at 260-300 ms after onset. These results indicate that context-based expectations facilitate object recognition by disambiguating object representations in visual cortex.
The false mussels (Mytilopsis leucophaeata) can be mechanical carriers of the shrimp microsporidianEnterocytozoon hepatopenaei(EHP)
Authors: Munkongwongsiri Natthinee , Thepmanee Orawan , Lertsiri Kanokwan , Vanichviriyakit Rapeepun , Itsathitphaisarn Ornchuma , Sritunyalucksana Kallaya
Published: April 2021

Enterocytozoon hepatopenaei(EHP) is an obligate intracellular parasite causing hepatopancreatic microsporidiosis (HPM) in cultivated shrimp in Asian countries. One strategy to control EHP is to identify and eliminate biological reservoir(s) in shrimp ponds. Several marine and brackish-water organisms, including false mussels (Mytilopsis) have been reported to test positive for EHP using polymerase chain reaction (PCR) technology. Thus, we tested samples of commonly found Thai false musselMytilopsis leucophaeatafrom 6 EHP-infected shrimp ponds by PCR for the presence of EHP using the spore wall protein (SWP) gene primers. The mussel samples from all 6 ponds were positive. Subsequent bioassays carried out using naïve mussels cohabitated with EHP-infected shrimp gave 100% SWP-PCR positive mussels at 20 days. One batch of such PCR-positive mussels was transferred for cohabitation with naïve shrimp and gave 37.5% EHP-positive shrimp within 10 days. Tissue analysis of the EHP-PCR-positive mussels using light microscopy,in situhybridization analysis for the SWP gene and electron microscopy did not confirm EHP infection. In summary, we obtained no evidence thatMytilopsis leucophaeatawas itself infected with EHP. However, it was apparently capable carrying infectious spores for some period after ingestion and serving as a mechanical or passive carrier. The results support previous reports warning of the danger of feeding living or fresh bivalves to broodstock shrimp in hatcheries or shrimp in rearing ponds without prior heating or freezing.
Safety and efficacy of Pulmonary physiotherapy in hospitalized patients with severe COVID-19 pneumonia (PPTCOVID Study): A prospective, randomised, single-blind, controlled trial
Authors: Javaherian Mohammad , Shadmehr Azadeh , Keshtkar Abbasali , Beigmohammadi Mohammad-Taghi , Dabbaghipour Narges , Syed Aabis , Moghadam Behrouz Attarbashi
Published: April 2021

Background

Pulmonary physiotherapy (PPT) is an important treatment in the management of patients with different types of pulmonary disorders. We aimed to evaluate safety and efficacy of PPT in hospitalized patients with severe COVID-19 pneumonia.

Methods

In this randomised, single-blind, controlled trial, we enrolled hospitalized, non-intubated patients (18 to 75 years with oxygen saturation (Spo2) in free-air breathing ≤90%) with COVID-19 pneumonia at a referral hospital. Participants were randomly assigned (1:1) to receive PPT (six sessions PPT with breathing exercises and airway clearance techniques) or basic care. The primary outcomes were venous blood O2 (pO2) and CO2 (pCO2) pressures, Spo2, and three-minute walking test (3MWT) that were assessed before and end of sixth session. Secondary outcomes included level of dyspnea, venous blood PH, one-month mortality, three-month mortality and short form-36 (SF-36) after one and three months. The assessor was blinded to the assignment. This trial is registered with ClinicalTrials.gov (NCT04357340).

Findings

In April-May 2020, 40 participants were randomly assigned to PPT or basic care groups. While at the end of intervention, pO2 (adjusted mean difference to baseline measure (AMD) 6.43 mmHg [95%CI 2.8, 10.07], P<0.01), Spo2 (AMD 4.43% [95%CI 2.04, 6.83], P=0.0011), and 3MTW (AMD 91.44 m [95%CI 68.88, 113.99], P<0.01) were higher in PPT group and basic care group, pCO2 was not improved (AMD -2.1 mmHg [95%CI-6.36, 2.21], P=0.33). Mortality rate was 20% (OR adjusted to baseline Spo2 .19 [95%CI .03, 1.30], P=.09) and 25% (OR adjusted to baseline Spo2 .16 [95%CI .26, 1.05], P=.056) lower in the PPT group at three-month at one-month and three-month, respectively. There were no significant differences in most SF-36 domains scores after one and three months. No serious adverse event was observed during PPT sessions.

Conclusion

Early PPT can be considered a safe and effective therapeutic choice for patients with severe COVID-19.
Reduced Reflex Autonomic Responses following Intradetrusor OnabotulinumtoxinA Injections: A pre/post study in Individuals with Cervical and Upper Thoracic Spinal Cord Injury
Authors: Dorey Tristan W. , Walter Matthias , Krassioukov Andrei V
Published: April 2021

Importance

Urodynamic studies (UDS) can provoke autonomic dysreflexia (AD) in individuals with spinal cord injury (SCI) at and above the sixth thoracic (T6) spinal segment potentially leading to profound vagally mediated heart rate reductions. Intradetrusor onabotulinumtoxinA injections have been shown to reduce AD events during UDS in this cohort but evidence is lacking whether this treatment can improve reflex autonomic responses.

Objective

To assess the effects of intradetrusor onabotulinumtoxinA injections on heart rate variability (HRV) responses to UDS in individuals, 18-65 years of age, with chronic (>1-year) SCI at or above T6 with confirmed neurogenic detrusor overactivity and AD during UDS.

Design, Setting, and Participants

This cohort study used participants from our recent prospective phase IV clinical trial. Individuals were screened at an academic medical centre between November 2014 and December 2019. After enrollment, participants underwent UDS prior to (i.e., baseline) and one month after intradetrusor onabotulinumtoxinA injections (post-treatment).

Interventions

OnabotulinumtoxinA (200 U) was injected into the detrusor muscle at 20 sites (10 U/site).

Main Outcomes and Measures

Continuous electrocardiogram (ECG) and blood pressure (BP) recordings were used to assess RR-interval, time and frequency domain metrics of HRV (a surrogate marker of autonomic nervous system activity), and AD pre- and post-intervention.

Results

A total of 19 participants with SCI (5 women; mean [SD] age 42 [8.3] years) with complete ECG and BP data sets were suitable for autonomic analysis. During baseline UDS, an increase in RR-interval (adjusted mean difference, -0.08; 95% CI, -0.14 to -0.03; P=0.002) as well as time and frequency domain metrics of HRV were detected. Vagally mediated increases in high frequency (HF) power during UDS were larger in participants with cervical SCI compared to upper thoracic SCI (adjusted mean difference, 20.3; 95% CI, 3.3 to 37.2; P=0.013). Intradetrusor onabotulinumtoxinA injections significantly reduced time domain metrics of HRV and HF power (adjusted mean difference, 9.1; 95% CI, 3.1 to 15.1, P<0.01) responses to UDS across all participants.

Conclusions and Relevance

Changes in HRV during UDS could be a potential indicator of improved autonomic cardiovascular function following interventions such as intradetrusor onabotulinumtoxinA injections.

Trial Registration

ClinicalTrials.gov Identifier: NCT02298660
A divergent protein kinase A in the human pathogenLeishmaniais associated with cell cortex microtubules and controls cell shape
Authors: Fischer Weinberger R. , Bachmaier S. , Ober V. , Githure G.B. , Dandugudumula R. , Phan I.Q. , Almoznino M. , Polatoglou E. , Tsigankov P. , Nitzan Koren R. , Myler P.J. , Boshart M. , Zilberstein D.
Published: April 2021

Parasitic protozoa of the genusLeishmaniacycle between the phagolysosome of mammalian macrophages, where they reside as rounded intracellular amastigotes, and the midgut of female sand flies, which they colonize as elongated extracellular promastigotes. Previous studies indicated that protein kinase A (PKA) plays an important role in the initial steps of promastigote development into amastigotes. Here, we describe a novel regulatory subunit of PKA (which we have named PKAR3) that is unique toLeishmaniaand most (but not all) other Kinetoplastea. PKAR3 is localized to subpellicular microtubules (SPMT) in the cell cortex, where it recruits a specific catalytic subunit (PKAC3). Promastigotes ofPKAR3orPKAC3null mutants lose their elongated shape and are round but remain flagellated. Truncation of an N-terminal formin homology-like domain of PKAR3 results in its detachment from the SPMT, also leading to rounded promastigotes. Thus, the tethering of PKAC3 kinase activity via PKAR3 at the cell cortex is essential for maintenance of the elongated shape of promastigotes. This role of PKAR3 is reminiscent of PKARIβ and PKARIIβ binding to microtubules of mammalian neurons, which is essential for the elongation of dendrites and axons, respectively. Interestingly, PKAR3 does not bind cAMP but nucleoside analogs with a very high affinity similar to the PKAR1 isoform ofTrypanosoma. We propose that these early diverged protists have re-purposed PKA for a novel signaling pathway that spatiotemporally controls microtubule remodeling and cell shapeviaPKA activity.
Structure-activity mapping of the peptide- and force-dependent landscape of T-cell activation
Authors: Feng Yinnian , Zhao Xiang , White Adam K. , Garcia K. Christopher , Fordyce Polly M.
Published: April 2021

Adaptive immunity relies on T lymphocytes that use αβ T-cell receptors (TCRs) to discriminate amongst peptides presented by MHC molecules (pMHCs). An enhanced ability to screen for pMHCs capable of inducing robust T-cell responses could have broad applications in diagnosing and treating immune diseases. T cell activation relies on biomechanical forces to initiate triggering of the TCR. Yet, mostin vitroscreening technologies for antigenic peptides test potential pMHCs for T cell binding without force and thus are often not predictive of activating peptides. Here, we present a technology that uses biomechanical force to initiate T cell triggering in high throughput. BATTLES (Biomechanically-AssistedT-cellTriggering forLarge-scaleExogenous-pMHCScreening) displays candidate pMHCs on spectrally encoded ‘smart beads’ capable of applying physiological loads to T cells, facilitating exploration of the force- and sequence-dependent landscape of T-cell responses. BATTLES can be used to explore basic T-cell mechanobiology and T cell-based immunotherapies.
Hotspots of pest-induced US urban tree death, 2020-2050
Authors: Hudgins Emma J. , Koch Frank H. , Ambrose Mark J. , Leung Brian
Published: April 2021

Urban trees are important nature-based solutions for future wellbeing and livability but are at high risk of mortality from insect pests. In the United States (US), 82% of the population live in urban settings and this number is growing, making urban tree mortality a matter of concern for most of its population. Until now, the magnitudes and spatial distributions of risks were unknown.

Here, we combine new models of street tree populations in ∼30,000 US communities, species-specific spread predictions for 57 invasive insect species, and estimates of tree death due to insect exposure for 48 host tree genera.

We estimate that 1.4 million street trees will be killed by invasive insects from 2020 through 2050, costing an annualized average of US$ 30M. However, these estimates hide substantial variation: 23% of urban centers will experience 95% of all insect-induced mortality. Further, 90% of all mortality will be due to emerald ash borer (Agrilus planipennis, EAB), which is expected to kill virtually all ash trees (Fraxinusspp.) in >6000 communities.

We define an EAB high-impact zone spanning 902,500km2, largely within the southern and central US, within which we predict the death of 98.8% of all ash trees. “Mortality hotspot cities” include Milwaukee, WI; Chicago, IL; and New York, NY.

We identify Asian wood borers of maple and oak trees as the highest risk future invaders, where a new establishment could cost US$ 4.9B over 30 years.

Policy implications:To plan effective mitigation, managers must know which tree species in which communities will be at the greatest risk, as well as the highest-risk insects. We provide the first country-wide, spatial forecast of urban tree mortality due to invasive insect pests. This framework identifies dominant pest insects and spatial impact hotspots, which can provide the basis for spatial prioritization of spread control efforts such as quarantines and biological control release sites. Our results highlight the need for EAB early-detection efforts as far from current infestations as Seattle, WA. Further, these findings produce a list of biotic and spatiotemporal risk factors for future high-impact US urban forest insect pests.
Encoding model for continuous motion-sensitive neurons in the intermediate and deep layers of pigeon Optic Tectum
Authors: Wang Songwei , Zhao Mengyu , Qian Longlong , Wang Zhizhong , Shi Li
Published: April 2021

There are typical neurons in the intermediate and deep layers of the optic tectum of avian, which are sensitive to small continuous moving targets. Based on this sensitivity of these neurons to continuous moving targets, the hypothesis of directed energy accumulation in dendrite field of these neurons is proposed. Based on the phenomenon that single dendrite activation can induce somatic spikes in vitro, the hypothesis of sequential probability activation mechanism of soma is proposed. Combined with the above hypotheses, the information encoding model of these typical neurons is constructed. Moreover, electrophysiological experiments and model simulations are carried out to obtain the response of neurons to visual stimuli of sequential motion, random motion and random sequential motion. Results show that the encoding model fits the response properties of continuous motion-sensitive neurons well. This study is of great significance for understanding the neurophysiological process of small-target perception for avian tectofugal pathway and the construction of the brain-inspired small-target detection algorithm.