bluuebunny/crossref_metadata_2025 huggingface dataset:
Hemosuccus Pancreaticus Following Acute Pancreatitis in a 12-years-old Boy Secondary to Pancreatic Pseudoaneurysm Treated With Endovascular Coil Embolization
Authors: Ekezie Christiana , Gill Kara G. , Pfau Patrick R. , Johannes Andrew R. , Woods Michael , Pinchot Jason , Furuya Katryn N. , O’Connell Daniel M. , Ratchford Thomas , Sigurdsson Luther , Walkiewicz Dorota , Valentyne Alyssa , St. Clair Nicole E. , Ehlenbach Mary L. , Woodring Therese , Danko Istvan
Published: October 2021

Hemosuccus pancreaticus is a very rare cause of upper gastrointestinal bleeding in children. It is defined as bleeding from the pancreatic or peripancreatic vessels into the main pancreatic duct and may be life-threatening. We present the case of a 12-year-old boy with hematemesis and severe anemia that developed following an episode of acute pancreatitis. Upper endoscopy did not reveal a bleeding source. An endoscopic retrograde cholangiopancreatography performed for the evaluation of common bile duct obstruction identified bleeding from the pancreatic duct. Subsequently, the bleeding source, a pseudoaneurysm of the splenic artery, was identified by conventional angiography and occluded with coil embolization. The diagnosis of hemosuccus pancreaticus may be difficult in children due to rare occurrence and the unusual anatomical site; hence, a high index of suspicion is needed in a patient with a history of pancreatitis who presents with intermittent upper gastrointestinal bleeding and normal upper endoscopy.
Association of Antibiotic Usage With Food Protein-Induced Enterocolitis Syndrome Development From a Caregiver’s Survey
Authors: Boyer Jeanelle , Sgambelluri Lizzy , Yuan Qian
Published: October 2021

Background:

Food protein-induced enterocolitis syndrome (FPIES) is a frequently misdiagnosed, serious, non-IgE–mediated food allergy, and the precise mechanism of disease is unknown. Acute FPIES typically presents with repetitive, profuse vomiting approximately 1 to 4 hours post-ingestion of a food trigger. Chronic FPIES is considered less common and less well characterized.

Objective:

We aimed to better describe FPIES and identify factors that may influence FPIES development through use of a self-reported, caregiver’s survey.

Methods:

FPIES and allergy-free infant caregivers completed a survey regarding lifestyle factors that may influence allergy acquisition such as antibiotic usage and delivery mode. FPIES caregivers reported symptoms, number of food triggers, type of FPIES, and symptoms from breastmilk ingestion. FPIES infants were compared to allergy-free infants to identify factors potentially associated with FPIES.

Results:

Infant and prenatal maternal antibiotic usage was higher in FPIES infants compared to allergy-free infants (43.8% versus 20.6% and 48.8% versus 23.57%, respectively; P < 0.05). When compared to infants with acute FPIES alone, infants described as both acute and chronic FPIES reported earlier onset of symptoms, more nonspecific symptoms, and symptoms triggered by breast milk, more antibiotic exposure, and more food triggers (P < 0.05).

Conclusion:

Antibiotic usage was significantly higher in FPIES infants when compared to allergy-free infants. Work is needed to elucidate the role of antibiotic usage in the etiology of FPIES. Infants reported to have both acute and chronic FPIES were significantly different from infants with acute FPIES alone, highlighting the need to more closely examine these different subtypes of FPIES.
The Influence of Age on Propofol Dosing Requirements During Procedural Sedation in the Emergency Department
Authors: Wells Maegan E. , Barnes Ryan M. , Caporossi Jeffrey , Weant Kyle A.
Published: October 2021

Propofol is a frequently used agent for procedural sedation in the emergency department (ED). Some have suggested that propofol dosing in this setting should be adjusted in elderly patients; however, limited data exist supporting this recommendation. Additional factors that may contribute to altered propofol dose requirements in this setting have not been thoroughly explored. The objective of this analysis was to ascertain the effect age may have on the propofol dose required during procedural sedation in the ED. This retrospective study was conducted at a Level 1 academic medical center ED and included patients 18 years or older who received propofol for procedural sedation from 2015 to 2017. Those patients who were 18–64 years of age were compared with those 65 years or older. Between the two groups, total and weight-based propofol requirements for sedation, opioid doses, and adverse events were compared. This analysis included 101 procedural sedations. The median induction dose and opioid requirements before or during the procedure were not significantly different between the two groups. Compared with patients 18–64 years of age, those 65 years or older had significantly less total weight-based propofol requirements (p = 0.024) and required less total propofol for sedation (p = 0.007). In addition, patients 65 years or older required fewer repeat doses of propofol during the procedure than younger patients (p = 0.043). The incidence of adverse effects, including respiratory suppression, was not significantly different between the two groups. Patients 65 years or older may have lower weight-based propofol dosing requirements than younger patients. Utilizing a reduced total dose and repeat dosing strategy for propofol in this setting may be indicated. Further investigations are recommended to clarify factors that signal the need for more tailored dosing.
Opioid-Related Risk Screening Measures for the Emergency Care Setting
Authors: Punches Brittany E. , Ali Abeer Alhaj , Brown Jennifer L. , Freiermuth Caroline E. , Clark Angela K. , Lyons Michael S.
Published: October 2021

Efforts to minimize the impact of prescribed opioids on future adverse outcomes are reliant on emergency care providers' ability to screen and detect opioid use disorder (OUD). Many prescriptions are initiated in the emergency department (ED) for acute pain; thus, validated measures are especially needed. Our systematic review describes the available opioid-related screening measures identified through search of the available literature. Measures were categorized by intent and applied clinical setting. We found 44 articles, identifying 15 screening measures. Of these, nine were developed to screen for current opioid misuse and five to screen for risk of future opioid misuse. None were created for use outside of a chronic pain setting. Many measures were applied differently from intended purpose. Although several measures are available, screening for adverse opioid outcomes in the ED is hampered by lack of validated instruments. Development of clarified conceptual models and ED-specific research is necessary to limit OUD.
Implementing Safe and Effective Pediatric Procedural Sedation in the Emergency Department
Authors: Jordan Kathleen S. , Steelman Sara H.
Published: October 2021

There has been a great increase in the number of diagnostic and therapeutic procedures performed in the emergency department (ED) setting over the past several decades. Most of these procedures are unscheduled, unplanned, and much more likely to be successful and result in a positive outcome when the child's pain, fear, anxiety, and movement are controlled. To promote patient quality and safety, increase the effectiveness and efficiency of care, and improve patient and caregiver satisfaction, there has been a proportionate increase in the number of pediatric procedural sedations performed in the ED. With proper education and skills verification, pediatric procedural sedation can be safely and efficaciously performed in the ED. The purpose of this article is to present an overview of pediatric analgesia, anxiolysis, and sedation to promote compassionate, evidence-based emergency care of children and optimize procedural performance and outcomes.
Reversal of Fortune: ECG STEMI Mimic
Authors: Sweeney Michael
Published: October 2021

This column discusses what appears to be a lead reversal in a 12-lead electrocardiogram (ECG) of a routine low-risk chest pain evaluation in a 36-year-old man. A 12-lead ECG was completed and identified ST changes suggestive of ischemia in the inferior leads. Findings in the ECG suggested arm lead reversal that created an ST-segment elevation myocardial infarction (STEMI) mimic. Repeating the ECG and correcting the arm lead mistake identified a correction of these changes and identified an ECG more suggestive of benign early repolarization or J-point elevation. This case discusses the importance of identifying ECG findings that may suggest arm lead reversal and how sometimes misplaced leads could create the appearance of an STEMI. This is a review of the case, key points to interpreting ECGs for possible lead reversal and identifying the REVERSE mnemonic.
The role of DDK and Treslin–MTBP in coordinating replication licensing and pre-initiation complex formation
Authors: Volpi Ilaria , Gillespie Peter J. , Chadha Gaganmeet Singh , Blow J. Julian
Published: October 2021

Treslin/Ticrr is required for the initiation of DNA replication and binds to MTBP (Mdm2 Binding Protein). Here, we show that in
Xenopus
egg extract, MTBP forms an elongated tetramer with Treslin containing two molecules of each protein. Immunodepletion and add-back experiments show that Treslin–MTBP is rate limiting for replication initiation. It is recruited onto chromatin before S phase starts and recruitment continues during S phase. We show that DDK activity both increases and strengthens the interaction of Treslin–MTBP with licensed chromatin. We also show that DDK activity cooperates with CDK activity to drive the interaction of Treslin–MTBP with TopBP1 which is a regulated crucial step in pre-initiation complex formation. These results suggest how DDK works together with CDKs to regulate Treslin–MTBP and plays a crucial in selecting which origins will undergo initiation.
Identification of epidemic scarlet fever group A Streptococcus strains in the paediatric population of Houston, TX, USA
Authors: Cubria M. Belen , Delgado Jose , Shah Brittany J. , Sanson Misu A. , Flores Anthony R.
Published: October 2021

Scarlet fever (SF) has recently been associated with group A streptococcal (GAS) strains possessing multidrug resistance and specific streptococcal exotoxins. We screened a local surveillance collection of GAS emm12 strains in Houston, TX, USA for antimicrobial resistance and identified a single isolate matching the antimicrobial resistance pattern previously reported for SF clones. Using whole-genome sequencing and combining genome sequence data derived from national surveillance databases, we identified additional emm12 GAS clones similar to those associated with prior SF outbreaks, emphasizing the need for continued surveillance for epidemic emergence in the USA.
Opioid Use Stigmatization and Destigmatization in Healthcare Professional Social Media
Authors: Graham S. Scott , Conway Fiona N. , Bottner Richard , Claborn Kasey
Published: October 2021

Stigmatization of opioid use constitutes a significant barrier to addressing the opioid crisis. Increasing use of social media by healthcare professionals provides an opportunity to foster destigmatization. However, little is known about stigmatization and destigmatization within healthcare professional social media communities. Accordingly, this study investigates the use of stigmatizing and destigmatizing language in three such communities: Medical Twitter, Public Health Twitter, and Epidemiology Twitter. Using a dataset of 2,319 tweets discussing opioids and associated with these Twitter communities, we analyzed each tweet for evidence of stigmatizing or destigmatizing language based on guidance from the National Institute on Drug Abuse. The results indicate that overall use of both stigmatizing and destigmatizing language is currently low across communities compared to the overall volume of opioid-related content. Additionally, there are measurable changes in stigmatizing and destigmatizing language on quarterly bases between 2012 and 2020. During this time, Public Health Twitter has seen a quarterly 19% reduction in rates of stigmatizing (IRR = 0.81, 95% CI 0.67 to 0.97), and all communities have experienced a quarterly 57% increase in destigmatizing language (IRR = 1.57, 95% CI: 1.33 to 1.85). This study also reveals that tweets containing stigmatizing and destigmatizing language receive minimal user engagement (measured by likes, retweets, quote tweets, and comments). While the longitudinal findings on increasing use of destigmatizing language are promising, they also indicate a need for increased efforts to encourage broader use of destigmatizing language. Leveraging the social learning potentials of Twitter offers one promising pathway for future initiatives.
Environmental injustice - Neighborhood characteristics as confounders and effect modifiers for the association between air pollution exposure and cognitive function
Authors: Li Zhenjiang , Christensen Grace M. , Lah James J. , Marcus Michele , Russell Armistead G. , Ebelt Stefanie , Waller Lance A. , Huels Anke
Published: October 2021

Background

Air pollution has been associated with cognitive decline among the elderly. Previous studies have not evaluated the simultaneous effect of neighborhood-level socioeconomic status (N-SES), which can be an essential source of bias.

Objectives

We explored N-SES as a confounder and effect modifier in a cross-sectional study of air pollution and cognitive function among the elderly.

Methods

We included 12,058 participants age 50+ years from the Emory Healthy Aging Study in Metro Atlanta using the Cognitive Function Instrument (CFI) score as our outcome, with higher scores representing worse cognition. We estimated 9-year average ambient carbon monoxide (CO), nitrogen oxides (NOx), and fine particulate matter (PM2.5) concentrations at residential addresses using a fusion of dispersion and chemical transport models. We collected census-tract level N-SES indicators and created two composite measures using principal component analysis and k-means clustering. Associations between pollutants and CFI and effect modification by N-SES were estimated via linear regression models adjusted for age, education, race and N-SES.

Results

N-SES confounded the association between air pollution and CFI, independent of individual characteristics. We found significant interactions between all air pollutants and N-SES for CFI (p-values<0.001) suggesting that effects of air pollution differ depending on N-SES. Participants living in areas with low N-SES were most vulnerable to air pollution. In the lowest N-SES urban areas, interquartile range (IQR) increases in CO, NOx, and PM2.5 were associated with 5.4% (95%-confidence interval, -0.2,11.4), 4.9% (-0.4,10.4), and 9.8% (2.2,18.0) increases in CFI, respectively. In lowest N-SES suburban areas, IQR increases in CO, NOx, and PM2.5 were associated with higher increases in CFI, namely 13.4% (1.3,26.9), 13.4% (0.3,28.2), and 17.6% (2.8,34.5), respectively.

Discussion

N-SES is an important confounder and effect modifier in our study. This finding could have implications for studying health effects of air pollution in the context of environmental injustice.
Knowledge towards breast cancer, and breast self-examination practices and its barriers among university female students in Bangladesh: Findings from a cross-sectional study
Authors: Sarker Rumpa , Islam Md. Saiful , Moonajilin Mst. Sabrina , Rahman Mahmudur , Gesesew Hailay Abrha , Ward Paul R
Published: October 2021

Early diagnosis of breast cancer is the best approach towards its control that may result in alleviating related mortality and morbidity. This study aimed to evaluate knowledge about breast cancer and both practices and perceived barriers to breast self-examination among female university students in Bangladesh. A cross-sectional study was carried out with 400 female students of Jahangirnagar University, Bangladesh. Participants were sampled from female dormitories at the university from January to April 2020. Proportionate stratified random sampling was conducted to calculate the study sample from each dormitory. A pre-tested, semi-structured self-reported questionnaire was employed to collect data from participants during the survey periods. The questionnaire consists of demographic variables, items about knowledge about breast cancer, breast self-examination practices and its barriers. We applied descriptive and inferential statistics, and data were analyzed using SPSS. Participants aged between 18-26 years and comprised university students of 1st year (20%), 2nd year (24%), 3rd year (22%), 4th year (21%) and Master’s (14.%). 18% of them had reported positive family history (mother, aunt, sister/cousin, grandmother) of breast cancer. The overall mean score of total knowledge items was 15 (SD = 3) out of 43, with an overall correct rate of 34%. The mean score of total knowledge items was significantly higher (p<0.001) among Master’s students and students with family members who have breast cancer. Only one in five students (21%) ever practiced breast self-examination. The mean score of practice towards breast self-examination was significantly higher (p<0.001) among participants who reported having family member of breast cancer. It is noted that the total knowledge score about breast cancer and practice towards breast self-examination are significantly correlated with each other (r = 0.54; p<0.001). About 33% participants had reported that ‘lack of knowledge as the main barrier to practicing breast self-examination followed by ‘I do not have the symptoms’ (22%), and shyness/ uncomfortable feelings (17%). The study revealed low levels of knowledge about breast cancer and low breast self-examination practices. This implies the need of promotion and implementation of educational interventions programs that are social and culturally appropriate and suitable for specific age groups.
A capacity assessment of healthcare workers to provide second-line antiretroviral therapy in Malawi: 2016
Authors: Ng’ambi Wingston , Babaye Yusuf , Nyasulu Paul , Jahn Andreas , Kalua Thoko , Longwe-Ngwira Abiba , Odo Michael , Namakhoma Ireen , Nyirenda Rose , O’Malley Gabrielle
Published: October 2021

INTRODUCTION

According to the estimates by the World Health Organisation, Malawi is lagging behind for the number of patients that should have been on second-line ART. In settings like Malawi the low switching may be attributable to low knowledge of clinical assessment for first-line antiretroviral treatment (ART) failure. We analyzed the knowledge level of different cadres of health workers on the management of second-line ART.

METHODS

This cross-sectional study assessed whether the first-line ART providers were capable to provide second-line ART in Malawi. Descriptive statistics were conducted using STATA v15.0. The passing score was 80%. Associations were assessed using Chi-Square tests with a statistical significance set at P<0.05.

RESULTS

Of the 754 ART providers assessed, 290 (38%) were eligible to prescribe second-line ARVs. We observed significant differences for eligibility by cadre and district (P<0.001). Furthermore, 69% of the ART providers correctly identified second-line ARVs while 9% of the providers correctly chose second-line ARVs for management of different side-effects. Both competencies varied by cadre and district (P<0.001). Of the ART providers, 9% correctly interpreted the VL results which we found to significantly vary by cadre (P<0.001) and not districts. However, 78% of ART providers were able to prescribe correct dose of second-line ART which did not significantly vary by cadre (P=0.27). Spatial analysis showed Thyolo and Chiradzulu as high performing districts.

CONCLUSIONS

This assessment found that registered nurses had comparable knowledge to medical doctors with at least Bachelor of Medicine and Bachelor of Surgery and clinical officers with a Diploma in Clinical Medicine in most areas but not in correctly selecting second line ARVs. To strengthen task shifting approaches, capacity building should focus on how to correctly select second line regimen and interpret viral load results. Training activities should also consider regional and district-level variability in capacity.
Efficacy of Spirulina for Allergic Rhinitis
Authors: Batista Iury Gomes , Person Osmar Clayton , Bogar Priscila , Angélico Júnior Fernando Veiga
Published: October 2021

Introduction

Allergic rhinitis is a condition of high prevalence in the population and widely studied, with several treatments being consecrated for its control. Spirulina is a dietary supplement that modulates immune function, and has been shown to modulate the inflammatory response of allergic rhinitis.

Purpose

To evaluate spirulina in the treatment and control of allergic rhinitis.

Material and Methods

This is a systematic review of randomized clinical trials. Searches were performed for randomized clinical trials relating spirulina to allergic rhinitis in five electronic databases: Cochrane - Central Register of Controlled Trials - CENTRAL (2021), PUBMED (1966-2021), EMBASE (1974-2021), LILACS (1982-2021) AND SCOPUS (2021). Two investigators independently extracted data and assessed trial quality.

Results

Two clinical trials involving a total of 215 patients were included. Both studies assessed the efficacy of spirulina in improving allergic rhinitis as the primary outcome. The first study described a significant reduction in runny nose, nasal congestion and itching over time of medication use (p<0.001) and in the second study the prevalence of rhinorrhea (P = 0.021), nasal congestion or obstruction (P = 0.039) and decreased smell (P = 0.030) were significantly less in the experimental group than in the control group.

Conclusions

The included studies were in favor of the use of spirrulina. However, the level of evidence is very low and limited. We should have caution due to the small number of clinical trials and participants in these studies. It is recommended to carry out new RCTs following the CONSORT standardization.
Combining faecal immunochemical testing with blood test results to identify patients with symptoms at risk of colorectal cancer: a consecutive cohort of 16,604 patients tested in primary care
Authors: Withrow Diana R , Shine Brian , Oke Jason , Tamm Andres , James Tim , Morris Eva , Davies Jim , Harris Steve , East James E , Nicholson Brian D
Published: October 2021

Structured abstract

Objective

Faecal immunochemical tests (FITs) are used to triage primary care patients with low risk colorectal cancer symptoms for referral to colonoscopy. The aim of this study was to determine whether combining FIT with routine blood test results could improve the performance of FIT in the primary care setting.

Design

Results of all consecutive FITs requested by primary care providers between March 2017 and December 2020 were retrieved from the Oxford University Hospitals NHS Foundation Trust. Demographic factors (age, sex), reason for referral, and results of blood tests within 90 days were also retrieved. Patients were followed up for incident colorectal cancer in linked hospital records. The sensitivity, specificity, positive and negative predictive values of FIT alone, FIT paired with blood test results, and several multivariable FIT models, were compared.

Results

Among 16,604 eligible patients, 139 colorectal cancers were diagnosed (0.8%). Sensitivity and specificity of FIT alone at a threshold of 10 µg Hb/g were 92.1% and 91.5% respectively. Compared to FIT alone, blood test results did not improve the performance of FIT. Pairing blood test abnormalities with FIT reduced the number of abnormal results needed to detect one cancer but increased the number of cancers missed. Multivariable models retaining FIT, sex, and mean cell volume performed similarly to FIT alone.

Conclusion

FIT is a highly sensitive tool for identifying higher risk individuals presenting to primary care with lower risk symptoms. Combining blood test results with FIT does not appear to lead to better discrimination for colorectal cancer than using FIT alone.
Response to the coronavirus disease 2019 (COVID-19) pandemic at private retail pharmacies in Kenya: a mixed methods study
Authors: Mugo Peter , Mumbi Audrey , Munene Daniella , Nzinga Jacinta , Molyneux Sassy , Barasa Edwine
Published: October 2021

Background

Private retail pharmacies in developing countries present a unique channel for COVID-19 prevention. We assessed the response to the COVID-19 pandemic by pharmacies in Kenya, aiming to identify strategies for maximising their contribution to the national response.

Methods

We conducted a prospective mixed-methods study, consisting of a questionnaire survey (n=195), a simulated client survey (n=103), and in-depth interviews (n=18). Data collection started approximately seven months after the pandemic reached Kenya. Quantitative data were summarized using measures of central tendency and multivariable modelling done using logistic regression. Qualitative analysis followed a thematic approach.

Results

The initial weeks of the pandemic were characterized by fear and panic among service providers and a surge in client flow. Subsequently, 61% of pharmacies experienced a dip in demand to below pre-pandemic levels and 31% reported challenges with unavailability, high price, and poor-quality of products. Almost all pharmacies were actively providing preventive materials and therapies; educating clients on prevention measures; counselling anxious clients; and handling and referring suspect cases. Fifty-nine pharmacies (55% [95% CI 45-65%]) reported ever receiving a client asking for COVID-19 testing and a similar proportion supported pharmacy-based testing. For treatment, most pharmacies (71%) recommended alternative therapies and nutritional supplements such as vitamin C; only 27% recommended conventional therapies such as antibiotics. While 48% had at least one staff member trained on COVID-19, a general feeling of disconnection from the national program prevailed.

Conclusions

Private pharmacies in Kenya were actively contributing to the COVID-19 response, but more deliberate engagement, support and linkages are required. Notably, there is an urgent need to develop guidelines for pharmacy-based COVID-19 testing, a service that is clearly needed and which could greatly increase test coverage. Roll-out of this and other pharmacy-based COVID-19 programs should be accompanied with implementation research in order to inform current and future pandemic responses.
A novel computational methodology for GWAS multi-locus analysis based on graph theory and machine learning
Authors: Saha Subrata , Singh Himanshu Narayan , Soliman Ahmed , Rajasekaran Sanguthevar
Published: October 2021

Background

Current form of genome-wide association studies (GWAS) is inadequate to accurately explain the genetics of complex traits due to the lack of sufficient statistical power. It explores each variant individually, but current studies show that multiple variants with varying effect sizes actually act in a concerted way to develop a complex disease. To address this issue, we have developed an algorithmic framework that can effectively solve the multi-locus problem in GWAS with a very high level of confidence. Our methodology consists of three novel algorithms based on graph theory and machine learning. It identifies a set of highly discriminating variants that are stable and robust with little (if any) spuriousness. Consequently, likely these variants should be able to interpret missing heritability of a convoluted disease as an entity.

Results

To demonstrate the efficacy of our proposed algorithms, we have considered astigmatism case-control GWAS dataset. Astigmatism is a common eye condition that causes blurred vision because of an error in the shape of the cornea. The cause of astigmatism is not entirely known but a sizable inheritability is assumed. Clinical studies show that developmental disorders (such as, autism) and astigmatism co-occur in a statistically significant number of individuals. By performing classical GWAS analysis, we didn’t find any genome-wide statistically significant variants. Conversely, we have identified a set of stable, robust, and highly predictive variants that can together explain the genetics of astigmatism. We have performed a set of biological enrichment analyses based on gene ontology (GO) terms, disease ontology (DO) terms, biological pathways, network of pathways, and so forth to manifest the accuracy and novelty of our findings.

Conclusions

Rigorous experimental evaluations show that our proposed methodology can solve GWAS multi-locus problem effectively and efficiently. It can identify signals from the GWAS dataset having small number of samples with a high level of accuracy. We believe that the proposed methodology based on graph theory and machine learning is the most comprehensive one compared to any other machine learning based tools in this domain.
Higher mortality associated with the SARS-CoV-2 Delta variant in the Western Cape, South Africa, using RdRp target delay as a proxy
Authors: Hussey Hannah , Davies Mary-Ann , Heekes Alexa , Williamson Carolyn , Valley-Omar Ziyaad , Hardie Diana , Korsman Stephen , Doolabh Deelan , Preiser Wolfgang , Maponga Tongai , Iranzadeh Arash , Engelbrecht Susan , Wasserman Sean , Schrueder Neshaad , Boloko Linda , Symons Greg , Raubenheimer Peter , Viljoen Abraham , Parker Arifa , Cohen Cheryl , Jassat Waasila , Lessells Richard , Wilkinson Robert J , Boulle Andrew , Hsiao Nei-yuan
Published: October 2021

A novel proxy for the Delta variant, RNA-dependent RNA polymerase target delay in the Seegene Allplex™ 2019-nCoV PCR assay, was associated with higher mortality (adjusted Odds Ratio 1.45 [95%CI 1.13-1.86]), compared to presumptive Beta infection, in the Western Cape, South Africa (April-July 2021). Prior diagnosed infection and vaccination were protective.
Mapping routine measles vaccination and factors related to uncompleted vaccination in Japan: An ecological study
Authors: Matsumoto Yuki
Published: October 2021

Objective

Few studies in Japan have considered regional differences in immunisation coverage and have geographically examined its distribution. We aimed to identify the municipal-level distribution of immunisation coverage and explore regional characteristics associated with its regional differences through ecological studies.

Design

An ecological study.

Setting

Japan municipalities.

Participants

All 1737 municipalities.

Outcome measure

The mean measles-rubella (MR) vaccination rate distribution from 2013 to 2018 was drawn using GIS. We tested the null hypothesis of non-random distribution using spatial autocorrelation analysis (Global Moran’s I). We presented clusters of municipalities with significantly higher and lower vaccination rates by hot spot analysis (Getis-Ord Gi*). Furthermore, we estimated among municipality characteristics, regional ones associated with vaccination rates.

Results

According to Global Moran’s I, the MR vaccine coverage distribution was clustered significantly (z = 11.44, p <0.00). Based on the hot spot analysis, the western Japan region tended to have more cold spots with low inoculation rates, small numbers of births and areas with considerable annual variations in vaccination rates. In multiple regression analysis using regional characteristics as independent variables, the 1-year and 6-month check-up rates (Model 2: 95% confidence interval [CI], 0.21-0.36), number of births (0.96-1.54), and standard deviation of the vaccination rate in a target year per municipality (0.17-0.24), were positively associated with the vaccination rate. Contrariwise, average mothers’ age (−1.15 to -0.34), percentage of single-parent households (−0.48 to -0.17), percentage of households with multiple children (−0.12 to -0.04), and moving-in rates (−0.26 to -0.05) were negatively associated with vaccination rate.

Conclusion

To eliminate regional differences in immunisation coverage, it is practical to identify areas with low immunisation coverage for a proactive corrective approach. The regional characteristics identified in this study, such as population structure, administrative characteristics, and trends in socioeconomic status in municipalities will make it possible to identify target areas.

Strengths and limitations of this study

The mean measles-rubella (MR) vaccination rate distribution from 2013 to 2018 was drawn using GIS.

We tested the null hypothesis of non-random distribution using spatial autocorrelation analysis (Global Moran’s I).

We presented clusters of municipalities with significantly higher and lower vaccination rates by hot spot analysis (Getis-Ord Gi*).

Furthermore, we estimated among municipality characteristics, regional ones associated with vaccination rates
The challenges of independence: ontogeny of at-sea behaviour in a long-lived seabird
Authors: Delord Karine , Weimerskirch Henri , Barbraud Christophe
Published: October 2021

The transition to independent foraging represents an important developmental stage in the life cycle of most vertebrate animals. Juveniles differ from adults in various life history traits and tend to survive less well than adults in most long-lived animals. Several hypotheses have been proposed to explain higher mortality including that of inadequate/inferior foraging skills compared to adults, young naïve individuals combining lack of experience and physical immaturity. Thus a change in behaviour, resulting in an improvement of skills acquired from growing experience, is expected to occur during a period of learning through the immaturity phase. Very few studies have investigated the ontogeny of foraging behaviour over long periods of time, particularly in long-lived pelagic seabirds, due to the difficulty of obtaining individual tracking data over several years. We investigated the foraging behaviour, through activity patterns, during the three life stages of the endangered Amsterdam albatross by using miniaturized activity loggers on naïve juveniles, immatures and adults. Naïve juveniles during their first month at sea after leaving their colony exhibited lower foraging effort (greater proportion of time spent sitting on water, longer and more numerous bouts on water, shorter and fewer flying bouts). Patterns of activity parameters in juveniles after independence suggested a progressive change of foraging performances during the first two months after fledging. We found sex differences in activity parameters according to time since departure from the colony and month of the year, consistent with the important sexual dimorphism in the Amsterdam albatross. Regardless of life stage considered, activity parameters exhibited temporal variability reflecting the modulation of foraging behaviour. This variability is discussed in light of both extrinsic (i.e. environmental conditions such as variability in food resources or in wind) and intrinsic (i.e. energetic demands linked to plumage renew during moult) factors.
Matching Adjusted Indirect Comparisons (MAICs) and Systematic Review: Efficacy and Safety of Experimental Chimeric Antigen Receptor (CAR) T-cells versus Axicabtagene ciloleucel (Yescarta) for the Treatment of Relapsed/Refractory Large B-Cell Lymphoma (LBCL)
Authors: Weinstein Bayarmagnai , Muresan Bogdan , Solano Sara , Vaz de Macedo Antonio , Lee YoonJung , Su Yu-Chen , Ahn Yeseul , Henriquez Gabriela , Camargo Cristina , Kim Gwang-Jin , Carpenter David O.
Published: October 2021

Despite favorable results of CAR T-cell therapy for relapsed/refractory large B-cell lymphoma (R/R LBCL), several challenges remain, including incomplete response, immune-mediated toxicity, and antigen-loss relapse. We delineated the relative clinical benefit of the novel approaches compared to the currently approved CAR T-cell therapies. In the absence of head-to-head comparisons and randomized controlled trials, we performed Matching Adjusted Indirect Comparisons to quantify the relative efficacy and safety of experimental CARs against Axicabtagene ciloleucel (Yescarta), the first FDA-approved CAR. A total of 182 R/R LBCL patients from 15 clinical trials with individual patient data (IPD) were pooled into eight populations by their CAR T-cell constructs and +/- ASCT status. The study endpoints were Progression-Free Survival (PFS), grade ≥ 3 cytokine release syndrome (CRS), and grade ≥ 3 neurotoxicity (NT). Tandem CD19.CD20.4-1BBζ CARs indicated favorable efficacy and safety, whereas the co-infusion of CD19 & CD20 with 4-1BBζ showed no clinical benefit compared to Yescarta. Third generation CD19. CD28. 4-1BBζ, and sequential administration of autologous stem cell transplantation (ASCT) and CD19. CARs presented statistically insignificant yet improved PFS and safety except for ASCT combined intervention which had suggestively higher NT risk than Yescarta. CARs with modified co-stimulatory domains to reduce toxicity (Hu19. CD8.28Zζ and CD19. BBz.86ζ) presented remarkable safety with no severe adverse events; however, both presented worse PFS than Yescarta. Third-generation CARs demonstrated statistically significantly lower NT than Yescarta. CD20. 4-1BBζ data suggested targeting CD20 antigen alone lacks clinical or safety benefit compared to Yescarta. Further comparisons with other FDA-approved CARs are needed.

NOVELTY AND IMPACT

Although currently approved CAR T-cells demonstrated unprecedently high response in relapsed / refractory LBCL in the salvage setting, lack of outcome durability and toxicity remain. We delineated the relative clinical benefit of the innovative experimental CAR T-cell approaches to Yescarta for insights into the ongoing efforts to address these inadequacies. Tandem CAR T-cells may provide higher efficacy and safer profile than Yescarta. Toxicity attenuated CAR T-cells present remarkable safety but no Progression-Free Survival (PFS) benefit.
Metabolic demand regulates selective cell death in Parkinson’s Disease
Authors: Zhao Luke , Nanal Ishaan , Wang Linxi , Looka Andrew , Bezaire Marianne
Published: October 2021

Parkinson’s Disease (PD) is a debilitating neurodegenerative condition that affects over 10 million people across the world, causing tremors and muscle weakness. Its mechanisms are unknown, but one key feature is selective cell death: neurons in the Substantia Nigra Pars Compacta (SNc) die, but their neighbors, the cells in the Ventral Tegmental Area (VTA), remain healthy. To study this phenomenon, we used an established single neuron model of the SNc, adapting its biophysical and bioenergetic properties to match that of the VTA. We discovered that reducing calcium influx correlates with higher ATP and lower ROS concentrations in the cell, suggesting in silico the importance of calcium influx in metabolic stress and selective vulnerability for Parkinson’s Disease. Future efforts may target calcium channel inhibition as a therapeutic strategy, although caution is needed with potential metabolic side effects.
Plant structural and nutritional responses to drought differ among common pasture species
Authors: Catunda Karen L. M. , Churchill Amber C. , Power Sally A. , Zhang Haiyang , Fuller Kathryn J. , Moore Ben D.
Published: October 2021

In the face of a changing climate, research indicates that more frequent and severe drought conditions are critical problems that will constrain production of high-quality forage and influence the performance of grazing animals in the future. In addition, the duration of drought and potential trade-offs between plant morphology and nutritional composition may influence plant drought adaptation strategies across pasture species, and the consequences for forage quality are not well understood. Here we present the results of a study investigating the effects of drought on biomass productivity, dead material, leaf:stem biomass allocation and nutritional composition (whole-plant and tissue-specific) across nine diverse pasture species. For this, we conducted a field experiment exposing species to a 6-month period of simulated severe drought (60% rainfall reduction during winter and spring) and samples were collected at multiple harvests. We found that drought had different, harvest-specific effects on plant biomass structure and nutritional composition among pasture species. The severity of drought impacts on productivity, but not on nutritional quality, increased with drought duration. In general, drought strongly reduced productivity, increased the percentage of dead material and had mixed effects (increases, decreases and no effect) on leaf:stem ratio and concentrations of crude protein, non-structural carbohydrates, neutral detergent fibre and lignin. Changes in plant-level nutritional quality were driven by simultaneous changes in both leaf and stem tissues for most, but not all, species. Our findings may be especially helpful for selection of adapted species/cultivars that could minimize potential drought risks on forage, thereby optimising pasture performance under future drought scenarios.
ReviewR: A light-weight and extensible tool for manual review of clinical records
Authors: Mayer David A. , Rasmussen Luke V. , Roark Christopher D. , Kahn Michael G. , Schilling Lisa M. , Wiley Laura K.
Published: October 2021

OBJECTIVES

Manual record review is a crucial step for electronic health record (EHR)-based research, but it has poor workflows and is error prone. We sought to build a tool that provides a unified environment for data review and chart abstraction data entry.

MATERIALS AND METHODS

ReviewR is an open-source R Shiny application that can be deployed on a single machine or made available to multiple users. It supports multiple data models and database systems, and integrates with the REDCap API for storing abstraction results.

RESULTS

We describe two real-world uses and extensions of ReviewR. Since its release in April 2021 as a package on CRAN it has been downloaded 2,204 times.

DISCUSSION AND CONCLUSION

ReviewR provides an easily accessible review interface for clinical data warehouses. Its modular, extensible, and open source nature afford future expansion by other researchers.

LAY SUMMARY

When doing research using data from electronic health records (EHRs), data may need to be extracted by hand, either to perform the study or to ensure its accuracy. However many researchers can’t access the EHR for this purpose. Even when researchers have access, they must flip between their review list, the EHR, and the location they are recording the results of their review, which is difficult and can cause errors. We developed a software application, ReviewR, to make this process easier and less error prone and have used it in two real-world projects.
Safety and Immunogenicity of the COVID-19 Vaccine BNT162b2 in Patients Undergoing Chemotherapy for Solid Cancer
Authors: Funakoshi Yohei , Yakushijin Kimikazu , Ohji Goh , Hojo Wataru , Sakai Hironori , Takai Ryo , Nose Taku , Ohata Shinya , Nagatani Yoshiaki , Koyama Taiji , Kitao Akihito , Nishimura Meiko , Imamura Yoshinori , Kiyota Naomi , Harada Kenichi , Tanaka Yugo , Mori Yasuko , Minami Hironobu
Published: October 2021

Background

Although COVID-19 severity in cancer patients is high, the safety and immunogenicity of the BNT162b2 mRNA COVID-19 vaccine in patients undergoing chemotherapy for solid cancers in Japan have not been reported.

Methods

We investigated the safety and immunogenicity of BNT162b2 in 41 patients undergoing chemotherapy for solid cancers and in healthy volunteers who received 2 doses of BNT162b2. We evaluated serum IgG antibody titers for S1 protein by ELISA at pre-vaccination, prior to the second dose and 14 days after the second vaccination in 24 cancer patients undergoing cytotoxic chemotherapy (CC group), 17 cancer patients undergoing immune checkpoint inhibitor therapy (ICI group) and 12 age-matched healthy volunteers (HV group). Additionally, inflammatory cytokine levels were compared between the HV and ICI groups at pre and the next day of each vaccination.

Results

Anti-S1 antibody levels were significantly lower in the ICI and CC groups than in the HV group after the second dose (median optimal density: 0.241 [0.063-1.205] and 0.161 [0.07-0.857] vs 0.644 [0.259-1.498], p = 0.0024 and p < 0.0001, respectively). Adverse effect profile did not differ among the three groups, and no serious adverse event occurred. There were no differences in vaccine-induced inflammatory cytokines between the HV and ICI groups.

Conclusion

Although there were no significant differences in adverse events in three groups, antibody titers were significantly lower in the ICI and CC groups than in the HV group. Further protection strategies should be considered in cancer patients undergoing CC or ICI.

Mini abstract

Titers of anti-S1 antibody after the second dose of BNT162b2 were significantly lower in patients with solid tumors undergoing active anticancer treatment than in the healthy volunteers.
Metacognitive insight into cognitive performance in pre and early-stage Huntington’s disease
Authors: Hewitt Samuel RC , White Alice J , Mason Sarah L , Barker Roger A
Published: October 2021

Objectives

Insight is an important predictor of quality of life in Huntington’s disease and other neurodegenerative conditions. However, estimating insight with traditional methods such as questionnaires is challenging and subject to limitations. This cross-sectional study experimentally quantified metacognitive insight into cognitive performance in Huntington’s disease gene-carriers.

Methods

We dissociated perceptual decision-making performance and metacognitive insight into performance in healthy controls (n=29), premanifest (n=19) and early-manifest (n=10) Huntington’s disease gene-carriers. Insight was operationalised as the degree to which a participant’s confidence in their performance was informative of their actual performance (metacognitive efficiency) and estimated using a computational model (HMeta-d).

Results

We found that pre and early-manifest Huntington’s disease gene-carriers were impaired in making perceptual decisions compared to controls. Gene-carriers required more evidence in favour of the correct choice to achieve similar performance and perceptual impairments were increased in those with manifest disease. Surprisingly, despite marked perceptual impairments, Huntington’s disease gene-carriers retained metacognitive insight into their perceptual performance. This was the case after controlling for confounding variables and regardless of disease stage.

Conclusion

We report for the first time a dissociation between impaired cognition and intact metacognition (trial-by-trial insight) in the early-stages of a neurodegenerative disease. This unexpected finding contrasts with the prevailing assumption that cognitive deficits are associated with impaired insight. Future studies should investigate how intact metacognitive insight could be used by some early Huntington’s disease gene-carriers to positively impact their quality of life.