bluuebunny/crossref_metadata_2025 huggingface dataset:
Intravenous Fosphenytoin Therapy as Acute Rescue Treatment for Glossopharyngeal Neuralgia Crisis in Patients Awaiting Neurosurgical Procedures: A Case Series
Authors: Noro Shusaku , Seo Yoshinobu , Honjo Kaori , Okuma Masahiro , Asayama Bunsho , Amano Yuki , Nakamura Hirohiko
Published: September 2022

Introduction

Few treatments exist for acute attacks of glossopharyngeal neuralgia (GPN). We investigated the efficacy of intravenous fosphenytoin therapy (IFT) during GPN crisis.

Case Presentation

We evaluated records of 4 consecutive patients with GPN awaiting microvascular decompression (MVD) who received IFT (total, 750 mg). Pain severity was evaluated using a Numerical Rating Scale (NRS). The score was 10 (maximum pain) before treatment. Case 1 (a 52-year-old woman, left GPN): for 12 hours after IFT, pain was eliminated (NRS 0/10); however, severe pain recurred 2 days later. She received MVD 9 days after IFT. Case 2 (a 72-year-old woman, right GPN): pain score reduced to 0/10 immediately after IFT and remained so for 2 days. Severe pain recurred, and she underwent MVD 4 days after IFT. Case 3 (a 69-year-old woman, right GPN): pain was reduced (NRS, 5/10) immediately after IFT and nearly eliminated (1/10) 1 hour later. After 6 hours, severe pain recurred; she received a second IFT 3 days later, and pain score dropped to 1/10. She was pain-free for 24 hours but intermediate pain recurred in 2 days. Microvascular decompression was performed 9 days after the second IFT. Case 4 (a 32-year-old woman, right GPN): Pain score reduced to 0/10 immediately after IFT and remained so for 4 days. She underwent MVD 4 days after IFT. No evidence of recurrence was found throughout the 24-, 22-, 20-, and 5-month follow-ups.

Conclusions

These results provide new insights into the innovative therapeutic option of intravenous fosphenytoin and contribute to advancements in treating acute GPN crisis.
Pressure injury prevention in the operating unit of a Swiss university hospital: a best practice implementation project
Authors: Perrenoud Beatrice , Maravic Philippe , Delpy Pierre
Published: September 2022

Objectives:

The aim of this project was to promote best practice in pressure injury prevention for patients during the intraoperative period in the main operating unit of a Swiss tertiary hospital, through improving risk assessment, safe positioning and documentation.

Introduction:

Pressure injury is a common and serious complication of surgery patients. Despite pressure injuries being mostly preventable, they are not a top priority of operating room professionals.

Methods:

A baseline audit was conducted using the JBI Practical Application of Clinical Evidence System, applying nine evidence-based criteria. The audit was followed by the implementation of multiple strategies to promote best practice in pressure injury prevention. A follow-up audit was conducted to determine the compliance with best practice recommendations.

Results:

The baseline audit indicated poor compliance with evidence-based practice in most audited criteria. The project team identified barriers to best practice and strategies implemented to improve practice, including tailored education, direct support in each surgery specialty, assignment of responsibilities regarding pressure injury prevention measures among the multidisciplinary team members and multiple channels of communication. Improvements in practice were observed in eight of nine criteria in the follow-up audit.

Conclusion:

The project demonstrated important positive changes in pressure injury prevention during the intraoperative period, despite a sharp slowdown in its implementation process. Continuing education for nursing and nonnursing practitioners has been systematized. Follow-up audits will need to be conducted in the future to maintain pressure injury prevention processes, and contribute to safety of care in adult patients during the perioperative period.
Electroconvulsive Therapy and Risk of Road Traffic Accidents
Authors: Hjerrild Simon , Jørgensen Martin Balslev , Dam Ole Henrik , Tehrani Elisabeth , Videbech Poul , Osler Merete
Published: September 2022

Objective

The aim of the study is to examine whether electroconvulsive therapy (ECT) was associated with the subsequent risk of being involved in a road traffic accident.

Methods

A cohort of all 375,435 patients older than 18 years with their first psychiatric hospital contact between 2003 and 2017 in the Danish National Patient Registry was followed for road traffic accidents until December 2018. Associations between ECT and road traffic accidents were examined using Cox regression analyses with multiple adjustments and using propensity score matching on sociodemographic and clinical variables.

Results

A total of 8486 patients (0.2%) were treated with ECT. During the median follow-up of 5.9 years, 778 of these patients (12.5%) were involved in a road traffic accident and the unadjusted incidence of road traffic accidents was lower among these patients (incidence rate, 15.5 per 1000 patient-years; 95% confidence interval [CI], 14.5–16.7) compared with patients not treated with ECT (incidence rate, 20.0 per 1000 patient-years; 95% CI, 20.0–20.3). Electroconvulsive therapy was not associated with road traffic accidents in the Cox regression models after adjustment for all covariables (hazard ratio, 1.00; 95% CI, 0.92–1.08) or in the propensity score–matched sample (hazard ratio, 0.91; 95% CI, 0.83–1.08). The HRs did not vary materially with follow-up time or when analyses were stratified on sex, age, or type of hospital contact.

Conclusions

The analysis of Danish National registry data indicates that ECT is not associated with the risk of being involved in major road traffic accidents.
Antiviral activity of salt-coated materials against SARS-CoV-2.
Authors: Coleman Christopher Michael , Wang Belinda , Wang Yixin , Tapia-Brito Emannuel , Chen Ziwei , Riffat James , Riffat Saffa , Tarlinton Rachael , Ghaemmaghami Amir
Published: September 2022

The SARS-CoV-2 pandemic demonstrated the importance of human coronaviruses and the need to develop materials to prevent the spread of emergent viruses. Here we describe that simple salt coating on a range of surfaces can degrade SARS-CoV-2.
Postoperative throat discomfort and associated factors among elective surgical patients at Ethiopian Teaching Hospitals
Authors: Chawaka Hunduma Jisha , Teshome Zenebe Bekele
Published: September 2022

Introduction

Throat pain and airway discomfort are the most commonly upsetting conditions of the patients’ wellbeing after surgery. However; little is known about the problem and associated factors.

Objective

To assess the magnitude, severity and associated factors of throat discomfort within 24 hours after surgery.

Design

Facility-based cross-sectional study was employed from July 01 to December 30, 2021. Data was extracted through patient interview and document review during the postoperative period.

Setting

The study was conducted at Ambo university referral hospital. On average, about six major elective surgical procedures are performed each day with a total of >1800 patients per year. The patients were scheduled from Orthopedic and trauma, General Surgery, Gynecologic, and Obstetric surgery department.

Participant

Using systematic sampling technique 370 elective surgical patients were recruited (k=2) and 36 were excluded from analysis; with incomplete data.

Result

The majority 63.2% (211) of the participants were females with a mean age of 35.7 + 9.7 years. The overall postoperative throat discomfort were observed in 122 (36.5%) and it were severe in 20.5% of them. However; the severity level declined over time 21.9% (21/96), 15.3% (18/118) and 5.6% (5/89); on the 1st, 6th hour and 24th hour, respectively. Utilization of larger ETT (AOR= 6.288, P= 0.001), surgery lasting > 2hours (AOR= 10.839, P= 0.000), awake extubation (AOR= 0.155, P=0.000), frequent episodes of hypotension (AOR= 13.220, P= 0.001), and less experienced anesthetist (AOR= 18.571, P=0.000); were significantly associated with throat discomfort.

Conclusion

Post-extubation throat discomfort complaints are high (36.5%). Due attention has to be given to minimize or prevent perioperative frequent episodes of hypotension, higher ETT size utilization, blood loss, and duration of surgery as much as possible. Patient reassurance with analgesia and orientation has to be considered during the postoperative time.
Early outcomes of a large four-year MDMPH program: Results of a cross sectional survey of graduates (from three cohorts)
Authors: Belkowitz Julia , Payoute Sabrina , Agarwal Gauri , Lichtstein Daniel , King Roderick , Shafazand Shirin , Chandran Latha
Published: September 2022

To address the public health needs of the 21st century, the University of Miami Miller School of Medicine implemented a four-year MD/ MPH program in 2011 with a mission to graduate public health physician leaders. The first cohort of students graduated in 2015. In the summer of 2020, a survey was sent to graduates to gather information on their early career involvement in the areas of leadership, research, and public health. In addition to several multiple-choice questions, the survey included an open-ended question on the impact of public health training in their careers. Content analysis was used to analyze the responses to the open-ended question. Eighty-two graduates completed the survey; 80 of whom had participated in residency training. Forty-nine (61%) joined a residency in a primary care field. Many graduates had leadership roles in their early careers, including 35 (44%) who were selected as chief residents. Fifty-seven (71%) participated in research, most commonly in quality improvement (40, 50%), clinical (34, 43%) and community based (19, 24%). Over one third (30, 38%) chose to do work in public health during residency.

Themes that emerged regarding the impact of public health training on their careers were: 1) Shift in perspective, 2) Value of specific skills related to public health, 3) Steppingstone for professional opportunities 4) Focus on health disparities, social determinants, and inadequacies of the healthcare system, 5) Status as leaders and mentors for peers, and 6) Self-efficacy during the pandemic. Graduates self-reported significant commitment and involvement in leadership, research, and public health as well as towards addressing some of our most pressing public health needs. Although long-term career outcomes need to be determined over time, currently graduates report significant benefits of their public health training for their professional outcomes.
Associations of habitual glucosamine use with SARS-CoV-2 infection and hospital admission and death with COVID-19: Evidence from a large population based cohort study
Authors: Meng Meijun , Wu Yanjun , Zeng Ruijie , Luo Dongling , Jiang Rui , Wu Huihuan , Zhuo Zewei , Yang Qi , Li Jingwei , Leung Felix W , Chen Qian , Sha Weihong , Chen Hao
Published: September 2022

Objectives

To assess the association of habitual glucosamine use with coronavirus 2 (SARS-CoV-2) infection, hospital admission, or mortality with Corona Virus Disease-19 (COVID-19) in a large population based cohort.

Design

Population based, prospective cohort study.

Setting

UK Biobank.

Participants

Participants with complete information on habitual glucosamine use and SARS-CoV-2 infection or COVID-19-related outcomes were included. These participants were registered from 2006 to 2010, followed up until 2022 and participated in SARS-CoV-2 tests between 2020 and 2022.

Main outcome measures

SARS-CoV-2 infection, COVID-19 hospital admission, and COVID-19 mortality.

Results

At baseline, 20,118 (15.9%) of the 126,518 participants reported as habitual glucosamine users. During the median follow-up 12.16 years, there were 53,682 cases of SARS-CoV-2 infection, 2,120 cases of COVID-19 hospital admission and 548 cases of COVID-19 mortality. The multivariate adjusted hazard ratios of habitual glucosamine users to non-users were 1.02 (95% confidence interval [CI] 0.99 to 1.05) for SARS-CoV-2 infection, 0.73 (95% CI 0.63 to 0.85) for COVID-19 hospital admission, and 0.74 (95% CI 0.56 to 0.98) for COVID-19 mortality. The Cox proportional hazard analysis after propensity-score matching yielded consistent results.

Conclusions

Habitual glucosamine use seems to be associated with a lower risk of hospital admission and mortality with COVID-19, but not the risk of SARS-CoV-2 infection.
Impact of sex in stroke in the young
Authors: Schwarzwald Anina , Fischer Urs , Seiffge David , Beyeler Morin , Scutelnic Adrian , Kaesmacher Johannes , Mordasini Pasquale , Dobrocky Tomas , Gralla Jan , Heldner Mirjam R , Umarova Roza , Meinel Thomas R , Arnold Marcel , Jung Simon , Simonetti Barbara Goeggel
Published: September 2022

Background and Purpose

Limited data is available on sex differences in young stroke patients describing discrepant findings. This study aims to investigate the sex differences in young stroke patients.

Methods

Prospective cohort study comparing risk factors, etiology, stroke localization, severity on admission, management and outcome in patients aged 16-55 years with acute ischemic stroke consecutively included in the Bernese stroke database between 01/2015 to 12/2018 with subgroup analyses for very young (16-35y) and young patients (36-55y).

Results

689 patients (39% female) were included. Stroke in women dominated in the very young (53.8%, p<0.001) and in men in the young (63.9%, p<0.001). As risk factors only sleep-disordered breathing was more predominant in men in the very young, whereas almost all risk factors were more predominant in men in patients older than 35y. The higher incidence of stroke in women in the very young may be explained by the sex specific risk factors pregnancy, puerperium, the use of oral contraceptives, and hormonal replacement therapy. Stroke severity at presentation, etiology, stroke localization, management, and outcome did not differ between women and men.

Conclusions

The main finding of this study is that sex specific risk factors in women may contribute to a large extent to the higher incidence of stroke in the very young in women. Almost all modifiable stroke risk factors are more prevalent in men, either in the young as well as in the very young. These findings have major implications for primary preventive strategies of stroke in young people.
Statistical Analysis Plan for Balanced versus Saline trialists living systematic review individual patient and aggregated data meta-analysis of randomized controlled trials (BEST-Living Study)
Authors: Zampieri Fernando G , Cavalcanti Alexandre B , Tanna Gian Luca Di , Damiani Lucas P , Hammond Naomi E , Machado Flavia R , Micallef Sharon , Myburgh John , Ramanan Mahesh , Rice Todd W , Semler Matthew W , Young Paul J , Finfer Simon
Published: September 2022

Purpose

The Balanced versus Saline Trialists (BEST) -Living Study is an ongoing living systematic review with aggregated and individual patient data meta-analysis (IPDMA) from eligible trials that assessed the effects of using balanced solutions compared with saline in critically ill adults. We herein present the search strategies for the BEST-Living Study and provide details for future analysis and presentation.

Methods

The report will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Individual Participant Data (PRISMA-IPD) recommendations. Search was performed in Pubmed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL). The primary endpoint will be hospital mortality, which will be analyzed using a Bayesian hierarchical model. Secondary endpoints include nurvival until longest follow-up available, use of kidney replacement therapy, and intensive care unit and hospital length-of-stay. Details on the analysis plan are provided in this statistical analysis plan.

Conclusion

The study will provide the most up-to-date and comprehensive assessment using the best evidence available for the use of balanced solutions in critically ill patients.

Approvals

The undersigned and all authors have reviewed this plan and approve it as final. They find it to be consistent with the requirements of the protocol as it applies to their respective areas. They also find it to be compliant with ICH-E9 principles and, in particular, confirm that this analysis plan was final prior to any analysis of the aggregated data.
Containing monkeypox on a college campus: a model-based analysis
Authors: Savinkina Alexandra , Chitwood Melanie , Kwon Jiye , Pitzer Virginia E. , Gonsalves Gregg , Paltiel A. David
Published: September 2022

We developed a stochastic dynamic transmission model of Monkeypox Virus (hMPXV) to simulate potential spread of hMPXV on a university campus. We used the model to evaluate containment strategies, including detection and isolation of cases and vaccination or quarantine of detected case contacts. We found that detection and isolation of cases was key to containing an outbreak and was able to avert 33%-85% of secondary infections depending on detection rate. Vaccination of known contacts was a useful strategy alongside isolation and detection and could prevent 50% of additional cases. Quarantine was found to have limited benefit.
A Deep Learning Model for Brain Age Prediction Using Minimally Pre-processed T1w-images as Input
Authors: Dartora Caroline , Marseglia Anna , Mårtensson Gustav , Rukh Gull , Dang Junhua , Muehlboeck J-Sebastian , Wahlund Lars-Olof , Moreno Rodrigo , Barroso José , Ferreira Daniel , Schiöth Helgi B. , Westman Eric ,   Alzheimer’s Disease Neuroimaging Initiative,   Australian Imaging Biomarkers and Lifestyle flagship study of ageing,   Japanese Alzheimer’s Disease Neuroimaging Initiative,   AddNeuroMed consortium
Published: September 2022

In the last few years, several models trying to calculate the biological brain age have been proposed based on structural magnetic resonance imaging scans (T1-weighted MRIs, T1w) using multivariate methods and artificial intelligence. We developed and validated a convolutional neural network (CNN)-based biological brain age prediction model that uses only one T1w MRI pre-processing step to simplify implementation and increase accessibility in research settings. Our model only requires rigid image registration to the MNI space, which is an advantage compared to previous methods that require more pre-processing steps, such as feature extraction. We used a multicohort dataset of cognitively healthy individuals (age range = 32.0 – 95.7 yrs.) comprising 17296 MRIs for training and evaluation. We compared our model using hold-out (CNN1) and cross-validation (CNN2-4) approaches. To verify generalizability, we used two external datasets with different population and MRI scan characteristics to evaluate the model. To demonstrate its usability, we included the external dataset’s images in the cross-validation training (CNN3). To ensure that our model used only the brain signal on the image, we also predicted brain age using skull-stripped images (CNN4). The trained models achieved a mean absolute error of 2.99, 2.67, 2.67, and 3.08 yrs. for the CNN1-4, respectively. The model’s performance in the external dataset was in the typical range of mean absolute error (MAE) found in the literature for testing sets. Adding the external dataset to the training set (CNN3), overall, MAE is unaffected, but individual cohort MAE improves (2.25 to 5.63 years). Salience maps of predictions reveal that periventricular, temporal, and insular regions are the most important for age prediction. We provide indicators for using biological (predicted) brain age as a metric for age correction in neuroimaging studies as an alternative to the traditional chronological age. In conclusion, using different approaches, our CNN-based model showed good performance using only one T1w brain MRI pre-processing step. The proposed CNN model is made publicly available for the research community to be easily implemented and used to study aging and age-related disorders.
Understanding the Experiences and Needs of LGBTIQA+ Individuals when Accessing Abortion Care and Pregnancy Options Counselling: A scoping review
Authors: Bowler Sally , Vallury Kari , Sofija Ernesta
Published: September 2022

Background

Safe, accessible, and inclusive abortion care and pregnancy options counselling are essential components of sexual and reproductive health and rights. Recent research has documented LGBTIQA+ people are as or more likely than the general population of women to experience an abortion in their lifetime yet face significant barriers to accessing abortion and related care which undermine wellbeing.

Aims

The present study undertakes a scoping review of research on the needs and experiences of the LGBTIQA+ population when accessing abortion care, pregnancy options, and post-abortion counselling, to support improved understanding of pregnant people’s preferences, needs, and experiences.

Materials and Methods

Online academic databases were searched using terms relating to gender identity and sexuality, abortion, pregnancy-options, and post-abortion counselling to identify peer reviewed papers published in English, from which we selected six publications from the United States, and one from Colombia that described experiences of LGBTIQA+ people accessing abortion-related care.

Results

Four of the seven studies reported in-depth or semi-structured interview studies while the remaining three examined cross-sectional surveys. Thematic analysis of all studies highlighted frequent discrimination and exclusion experienced by participants, healthcare avoidance, unsafe abortion, non-disclosure to providers, provision of poor quality of care, and poor health outcomes for LGBTIQA+ people.

Conclusions

Gender-inclusive services and training for health providers are key to the provision of safe and accessible abortion care, and imperative to overcome generations of mistrust held by the LGBTIQA+ community. Research into the needs of LGBTIQA+ people when accessing pregnancy options counselling is critically needed.

Key messages

LGBTIQA+ people experience exclusion, isolation, misgendering, and denial of care when accessing abortion, and barriers faced are compounded by socioeconomic status and race.

Poor provision of abortion care and negative experiences for this population result in deep mistrust of providers, non-disclosure of gender/sexuality, healthcare avoidance, and self-induced abortion.

Appropriate, inclusive, and accessible care requires gender affirming and inclusive services, educational materials, and intake forms, community consultation, and improved healthcare provider training and knowledge.
“Just Saiyan: Tail-trimming Human Monkeypox Virus Assemblies Emphasizes Resolvable Regions in Inverted Terminal Repeats to Improve the Resolution of Reference and Production Genomes for Genomic Surveillance”
Authors: Gener Alejandro R.
Published: September 2022

Our ability to track the spread of the human monkeypox virus (hMPXV) during the ongoing monkeypox (hMPX) outbreak of 2022 relies on the availability of high-quality reference genomes. However, the way the information content of these genomes is organized in genome databases leaves room for interpretation. A current limitation of hMPXV genomic analysis is that the variability occurring in the inverted terminal repeats (ITRs) cannot be effectively resolved. This is because of shortcomings of the leading short-read sequencing and reference-guided assembly and variant calling used in the ongoing global hMPXV outbreak surveillance effort. Here I propose ITR tail-trimming, a simple no-cost reframing of how we organize hMPXV reference genomes and future assemblies. This approach is based on long terminal repeat (LTR) tail-trimming, which is a common practice in HIV sequence analysis. The main point of repeat sequence trimming is to remove problematic sequences while paying attention to limitations of mapping and variant calling in remaining repeat-associated (but ideally no longer repetitive) sequence. ITR tail-trimming would neutralize ITRs as distracting features at the read- and assembly-levels, allowing the global community to focus our efforts to track variability across hMPXV genomes.
Hierarchical Two-Stage Cost-Sensitive Clinical Decision Support System for Screening Prodromal Alzheimer’s Disease and Related Dementias
Authors: Kleiman Michael J. , Ariko Taylor , Galvin James E. ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: September 2022

Background

The detection of subtle cognitive impairment in a clinical setting is difficult, and because time is a key factor in small clinics and research sites, the brief cognitive assessments that are relied upon often misclassify patients with very mild impairment as normal. In this study, we seek to identify a parsimonious screening tool in one stage, followed by additional assessments in an optional second stage if additional specificity is desired, tested using a machine learning algorithm capable of being integrated into a clinical decision support system.

Methods

The best primary stage incorporated measures of short-term memory, executive and visuospatial functioning, and self-reported memory and daily living questions, with a total time of 5 minutes. The best secondary stage incorporated a measure of neurobiology as well as additional cognitive assessment and brief informant report questionnaires, totaling 30 minutes including delayed recall. Combined performance was evaluated using 25 sets of models, trained on 1181 ADNI participants and tested on 127 patients from a memory clinic.

Results

The 5-minute primary stage was highly sensitive (96.5%) but lacked specificity (34.1%), with an AUC of 87.5% and DOR of 14.3. The optional secondary stage increased specificity to 58.6%, resulting in an overall AUC of 89.7% using the best model combination of logistic regression for stage 1 and gradient-boosted machine for stage 2.

Conclusions

The primary stage is brief and effective at screening, with the optional two-stage technique further increasing specificity. The hierarchical two-stage technique exhibited similar accuracy but with reduced costs compared to the more common single-stage paradigm.
Genomic epidemiology of SARS-CoV-2 infections in The Gambia, March 2020 to Jan 2022
Authors: Kanteh Abdoulie , Jallow Haruna S. , Manneh Jarra , Sanyang Bakary , Kujabi Mariama A. , Ndure Sainabou Laye , Jarju Sheikh , Sey Alhagie Papa , Damilare Dabiri K , Bah Yaya , Sambou Sana , Jarju Gibril , Manjang Buba , Jagne Abubacarr , Bittaye Sheikh Omar , Bittaye Mustapha , Forrest Karen , Tiruneh Desta Alamerew , Samateh Ahmadou Lamin , Jange Sheriffo , Hué Stéphane , Muhammed Nuredin , Amambua-Ngwa Alfred , Kampmann Beate , D’Alessandro Umberto , de Silva Thushan I. , Roca Anna , Sesay Abdul Karim
Published: September 2022

Background

COVID-19, caused by SARS-CoV-2, is one of the deadliest pandemics over the last 100 years. Sequencing is playing an important role in monitoring the evolution of the virus, including the detection of new viral variants. This study describes the genomic epidemiology of SARS-CoV-2 infections in The Gambia.

Methods

Nasopharyngeal and/or oropharyngeal swabs collected from suspected cases and travellers were tested for SARS-CoV-2 using standard RT-PCR methods. SARS-CoV-2 positive samples were sequenced following standard library preparation and sequencing protocols. Bioinformatic analysis was done using ARTIC pipelines and lineages assigned using Pangolin.

Findings

Between March 2020 to January 2022, there were almost 12,000 SARS-CoV-2 confirmed cases distributed into four waves, each of them lasting between 4 weeks and 4 months, with more cases during the rainy seasons (July-October). As shown by the 1643 sequenced samples, each wave occurred after new viral variants and/or lineages were introduced in The Gambia, generally those already established in Europe and/or in other African countries. Local transmission was higher during the first and third wave, with mostly B.1.416/Senegal/Gambian lineage and AY.34.1/Delta subtype, respectively. The second wave was driven by two variants, namely Alpha and Eta and B.1.1.420 lineage. The Omicron/fourth wave was the shortest.

Interpretation

Efficient surveillance, including strengthening entry points and screening asymptomatic individuals especially during the rainy seasons would be important to promptly detect and control future waves in The Gambia and the subregion.

Funding

Medical Research Unit The Gambia at LSHTM, UK Research and Innovation funding (grant reference MC_PC_19084), MRC/UKRI MC_PC_19084 and World Health Organisation.
Screening the use of DCA for the treatment of cancer in adult patients: a scoping review protocol
Authors: Bianchi Cecilia , Martinelli Romina P , Rozados Viviana R , Scharovsky O Graciela
Published: September 2022

Sodium dichloroacetate (DCA), a small-molecular-weight drug, is capable to shift the tumor metabolism by reactivating the oxidative phosphorylation in the mitochondria. As a consequence, apoptosis resistance in cancer cells decreased. Numerous studies have been performed in cell lines and animal models, to unveil its efficacy as an antitumor drug. It is also being studied in patients with different types of tumors, with a variety of doses and administration schedules. Even so, the lack of controlled studies makes the safety profile a concern. This scoping review aims to explore the existing scientific literature to provide an overview of the use of DCA (any dose, frequency, or route of administration) in adults with cancer. The search will be performed in MEDLINE/PubMed, and LILACS databases.

Additional data sources will be consulted. Two reviewers will screen all identified records for relevance, and chart the data using a data charting form. Findings will be reported according to PRISMA for Scoping Reviews (PRISMA-ScR). No quality assessment will be performed.
The profile and distribution of skin disorders in ambulatory community-dwelling adult patients with Schizophrenia: a study from North India
Authors: Varadharajan Natarajan , Narang Tarun , Rani Seema , Mehta Hitaishi , Kathiravan Sanjana , Singh Shubh Mohan
Published: September 2022

Introduction

Schizophrenia is a severe mental disorder. There is ample evidence to suggest that there are various multi-systemic co-morbidities in the patients with schizophrenia. However, data for dermatological comorbidities in these patients is scarce. This is relevant because of the common embryological basis of the central nervous system and skin, and also the disabling nature of schizophrenia itself.

Objective

To analyze the profile and distribution of cutaneous conditions in patients with schizophrenia.

Methods

Consecutive adult patients with schizophrenia attending the follow-up service of the outpatient clinic of the department of psychiatry of a tertiary hospital in North India were evaluated for the presence of a skin disorder by a dermatologist.

Results

Dermatological findings were seen in 71 patients (69.60%), 39 patients (38.23%) had multiple skin conditions. As a group, infections were the most prevalent diagnosis seen in 18 patients (17.64%) and fungal infections were commonly observed (n=14, 13.72%). Other common dermatoses were nevi, age related cutaneous changes, dyschromias and drug-induced acne. Among medical disorders, blood pressure was found to be elevated in 28 patients (27.45%) while sixty-four patients (69.74%) were either overweight or obese.

Conclusion

A high prevalence of dermatological diseases is seen in patients with schizophrenia. Both caregivers and psychiatrists managing these patients should familiarize themselves with these conditions and dermatology consultation should be sought for the prompt diagnosis and management.
The SumRank method efficiently detects valid pleiotropic variants using GWAS summary level data
Authors: Lamballais Sander , Roshchupkin Gennady V. , Poot Raymond A. , Kushner Steven A. , Ikram M. Arfan , Adams Hieab H. H. , Tiemeier Henning
Published: September 2022

Genome-wide association studies (GWASs) have illustrated that pleiotropy is the norm rather than the exception in the genetic architecture of complex traits. Previous methods have been proposed to investigate cross-trait associations; however, these typically suffer from substantially inflated false positive rates, are limited to associations between only two traits, or examine only a subset of genome-wide variants. Here, we introduce SumRank, a novel method for discovering cross-trait associations based on p-values from GWAS summary statistics. Using numerical and genotype simulations, we demonstrated that SumRank had a near-zero false positive rate, in contrast to contemporary meta-analytical approaches that yielded severely inflated rates. We applied SumRank to GWAS summary data of eight psychiatric disorders and identified 515 independent pleiotropic variants across 175 loci, of which 92 were novel and 71 had previously been associated with only one disorder. Overall, SumRank provides a valid and efficient method for genome-wide discovery of pleiotropic variants that underlie a scalable number of traits.
Optimal combinations of CSF biomarkers for predicting cognitive decline and clinical conversion in cognitively unimpaired participants and mild cognitive impairment patients: A multi-cohort study
Authors: Salvadó Gemma , Larsson Viktoria , Cody Karly A , Cullen Nicholas C. , Jonaitis Erin M , Stomrud Erik , Kollmorgen Gwendlyn , Wild Norbert , Palmqvist Sebastian , Janelidze Shorena , Mattsson-Carlgren Niklas , Zetterberg Henrik , Blennow Kaj , Johnson Sterling C. , Ossenkoppele Rik , Hansson Oskar
Published: September 2022

INTRODUCTION: Our objective was determining the optimal combinations of cerebrospinal fluid (CSF) biomarkers for predicting disease progression in Alzheimer's disease (AD) and other neurodegenerative diseases.

METHODS: We included 1,983 participants from three different cohorts with longitudinal cognitive and clinical data, and baseline CSF levels of Aβ42, Aβ40, p-tau, NfL, neurogranin, α-synuclein, sTREM2, GFAP, YKL-40, S100b and IL-6 (Elecsys® NeuroToolKit).

RESULTS: Change of modified Preclinical Alzheimer's Cognitive Composite (mPACC) in cognitively unimpaired (CU) was best predicted by p-tau/Aβ42 alone (R2≥0.31) or together with neurofilament light ([NfL],R2=0.25), while p-tau/Aβ42 (R2≥0.19) was sufficient to accurately predict change of the Mini-Mental State Examination (MMSE) in mild cognitive impairment (MCI) patients. P-tau/Aβ42 (AUC≥0.87) and p-tau/Aβ42 with NfL (AUC≥0.75) were the best predictors of conversion to AD and all-cause dementia, respectively.

DISCUSSION: P-tau/Aβ42 is sufficient for predicting progression in AD, with very high accuracy. Adding NfL improves the prediction of all-cause dementia conversion and cognitive decline.
Brain-Based Gene Expression of Putative Risk Genes for Anorexia Nervosa in the Human Brain
Authors: Murray Stuart B. , Rokicki Jaroslav , Sartorius Alina , Winterton Adriano , Andreassen Ole A. , Westlye Lars T. , Nagata Jason M. , Quintana Daniel S.
Published: September 2022

The etiology of anorexia nervosa (AN) remains elusive. Here, we characterize spatially distributed expression patterns of risk genes for AN in the human brain, developing whole-brain maps of AN gene expression. We found that genes associated with AN are most expressed in the brain, relative to all other body tissue types, and demonstrate gene-specific expression patterns which extend to cerebellar, limbic and basal ganglia structures in particular. fMRI meta-analyses reveal that AN gene expression maps correspond with functional brain activity involved in processing and anticipating appetitive and aversive cues.
Safety and immunogenicity of a third dose of COVID-19 protein subunit vaccine (Covovax™) after homologous and heterologous two-dose regimens
Authors: Kanokudom Sitthichai , Chansaenroj Jira , Suntronwong Nungruthai , Assawakosri Suvichada , Yorsaeng Ritthideach , Nilyanimit Pornjarim , Aeemjinda Ratchadawan , Khanarat Nongkanok , Vichaiwattana Preeyaporn , Klinfueng Sirapa , Thongmee Thanunrat , Katanyutanon Apirat , Thanasopon Wichai , Arayapong Jirawan , Withaksabut Withak , Srimuan Donchida , Thatsanatorn Thaksaporn , Sudhinaraset Natthinee , Wanlapakorn Nasamon , Honsawek Sittisak , Poovorawan Yong
Published: September 2022

Objective

To report the safety and immunogenicity profile of a protein subunit vaccine (Covovax™) given as a third (booster) dose to individuals primed with different primary vaccine regimens.

Methods

Individuals primed with two doses of COVID-19 vaccines for at least 3 months were enrolled and assigned to five groups according to their primary vaccine regimens: CoronaVac, BBIBP-CorV, AZD1222, BNT162b2, and CoronaVac/AZD1222. Immunogenicity analysis was performed to determine binding antibodies, neutralizing activity, and the T-cell response.

Results

Overall, 215 individuals were enrolled and boosted with the Covovax™ vaccine. The reactogenicity achieved was mild-to-moderate. Most participants elicited a high level of binding and neutralizing antibody responses against wild type and omicron variants following the booster dose. The 197 participants were classified by anti-N IgG. Of these, 141/197 (71.6%) were a seronegative population, and neutralizing activity and IFN-γ release were further monitored. A booster dose could elicit neutralizing activity to wild type and omicron variants by more than 95% and 70% inhibition at 28 days, respectively. The Covovax™ vaccine could elicit a cell-mediated immune response.

Conclusion

The protein subunit vaccine (Covovax™) can be proposed as a booster dose after two different priming dose regimens. It has strong immunogenicity and good safety profiles.
A JOURNEY THROUGH RURAL COMMUNITY RADIOGRAPHY PRACTICE IN SOUTH-SOUTH NIGERIA: RADIOGRAPHERS’ PERCEPTION, WILLINGNESS AND BARRIERS
Authors: Ogolodom Michael Promise , Mbaba Awajimijan Nathaniel , Maduka Beatrice Ukamaka , Iloka Chima Jude , Erondu Ikechukwu Felix , Eja-Egwu Uche Nathaniel , Alazigha Nengi , Brownson Egop Egop , Nwodo Victor Kelechi , Akhigbe Robert O.
Published: September 2022

Introduction

The lack of healthcare professionals and their retention in rural areas has become a serious concern to the health sector globally. Retaining health staff in rural areas has proven difficult as young professionals prefer urban postings. This study aimed to assess radiographers’ perception and willingness to work in rural areas of Rivers State.

Method

This cross-sectional questionnaire-based study was conducted among radiographers in Rivers State. The participants’ socio-demographic variables and their responses to willingness and perception to work in rural areas were obtained and analyzed.

Results

Only few 30% (n=12) of the respondents were willing to work in the rural areas of Rivers state. However, the majority of 95 %(n=38) of the respondents perceived extra payment as an incentive for them to be willing to work in the rural areas of this study location. Most 88 %(n=35) of the respondents perceived unfavorable working conditions in rural areas as a barrier to their willingness. A large proportion of 55 %(n=22) of the respondents stated that their marital status was a barrier to working in rural areas. More than half (85%, n=34) of the respondents perceived poor accommodation as a barrier to working in rural areas. The majority 88% (n=35) of the respondents stated that militant activities was a barrier to their willingness to work in the rural areas of Rivers State. There were statistically significant relationships between the evaluated respondent’s socio-demographic variables gender (χ2 = 48.000, p = 0.000), years of working experience (χ2 = 47.500, p = 0.000), marital status (χ2 = 84.966, p = 0.000) and age (χ2 = 76.758, p = 0.021) and their willingness to work in the rural areas of Rivers State.

Conclusion

The key findings suggest that the majority of the Radiographers were not willing to work in the rural areas of Rivers State. The reasons adduced for their strong disinclination were based on their perception of unfavorable working conditions in the rural areas. Nonetheless, they were of the opinion that financial inducement could influence their willingness to work in rural areas.
Higher-order epistasis creates idiosyncrasy, confounding predictions in protein evolution
Authors: Buda Karol , Miton Charlotte M. , Tokuriki Nobuhiko
Published: September 2022

Epistasis shapes evolutionary outcomes during protein adaptation. In particular, when the effects of single mutations or mutational interactions are idiosyncratic, that is, unique to a genetic background, the predictability of protein evolution becomes greatly impaired. Here, we unveil a quantitative picture of the prevalence and role of idiosyncrasy in protein evolution by analysing 45 protein fitness landscapes, generated from seven enzymes. We found that mutational effects and epistasis are highly idiosyncratic across the landscapes. Idiosyncrasy obscured functional predictions of mutated proteins when using limited mutational data, and often continued to impair prediction upon incorporation of epistatic information. We show that idiosyncrasy stems from higher-order epistasis, and highlight examples where it permits, or restricts, evolutionary accessibility of certain genotypes. Our work suggests that idiosyncrasy deeply confounds predictions in protein evolution necessitating its incorporation into predictive models and in-depth exploration of its underlying molecular mechanisms.
An optimized approach to study sub-sarcomere structure utilizing super-resolution microscopy with secondary VHH nanobodies
Authors: Douglas CM , Bird JE , Kopinke D , Esser KA
Published: September 2022

The sarcomere is the fundamental contractile unit in skeletal muscle, and the maintenance of its structure is critical for its function. While alterations in sarcomere structure are implicated in many clinical conditions of muscle weakness this area has made limited progress due, in part, to limitations in the ability to robustly detect and measure at sub-sarcomere resolution. Classically the field has relied on approaches including confocal and electron microscopy, but there are technique-specific limitations with respect to resolution, tissue morphology, and protein specific labeling. In this study, our goal was to establish a robust and reproducible method to probe sub-sarcomere protein localization in longitudinal muscle sections. We optimized several steps from tissue preparation to antibody selection and imaging to provide the ability to quantitatively assess spatial distribution of proteins within a single sarcomere. This includes 1) in situ fixation for structural integrity, 2) use of multiple same host-species primary antibodies with Fab fragment antibody blocking to maintain specificity, and 3) the use of super-resolution structured illumination microscopy (SIM) to improve from confocal, along with use of emergent VHH secondary nanobodies to double the resolution. The combination of these methods provides a unique approach to improve visualization of sarcomere structure while simultaneously providing the ability to rigorously probe protein localization. While this study focused on assessment of skeletal muscle structure and provides an important set of tools for analysis of skeletal muscle health in disease and aging, we suggest the methods herein may prove advantageous for research outside of skeletal muscle.
Musleblind-1 regulates microtubule cytoskeleton in C. elegans mechanosensory neuron through tubulin mRNAs
Authors: Puri Dharmendra , Samaddar Sarbani , Banerjee Sourav , Ghosh-Roy Anindya
Published: September 2022

Regulation of microtubule cytoskeleton is fundamental for the development and maintenance of neuronal architecture. Recent studies have shown that regulated RNA processing is also critical for the establishment and maintenance of neural circuits. In a genetic screen using mechanosensory neurons of C. elegans, we identified a mutation in muscleblind-1 as a suppressor of loss of kinesin-13 family microtubule destabilizing factor klp-7. Muscleblind-1(MBL-1) is an RNA-binding protein that regulates the splicing, localization, and stability of RNA. We found that mbl-1 is required cell-autonomously for axon growth and synapse formation in the posterior lateral microtubule (PLM) neuron. Loss of mbl-1 affects stability and plus-end-out organization of microtubules in the anterior process of PLM. These defects are also accompanied by abnormal axonal transport of the synaptic protein RAB-3 and loss of gentle touch sensation in mbl-1 mutant. Our data showed that mbl-1 is genetically epistatic to mec-7 (β tubulin) and mec-12 (a tubulin) for axon growth. The immunoprecipitation of MBL-1 pulls down the mec-7, mec-12, and sad-1 mRNAs. Additionally, the mbl-1 mutants show a reduction in the level and stability of mec-7 and mec-12 transcripts. Independently, mbl-1 is epistatic to sad-1 for synapse formation. Our work elucidated a previously unknown link between RNA binding protein and cytoskeletal machinery for the development and maintenance of the nervous system.
On the performance of multi-compartment relaxometry for myelin water imaging – Intra-subject and inter-protocol reproducibility
Authors: Chan Kwok-Shing , Chamberland Maxime , Marques José P.
Published: September 2022

We evaluate the test-retest repeatability and study the tissue properties of multicompartment relaxometry-based myelin water imaging (MCR-MWI) derived from different gradient echo (GRE) acquisition settings. Additionally, the variable flip angle acquisition scheme is optimised based on numerical simulations to reduce the acquisition time of MCR-MWI in a clinically practical range without using advanced image acquisition methods. For the test-retest analysis, in vivo imaging was performed to collect data from three healthy volunteers in two identical sessions. Three GRE sequence settings with different echo times and repetition times imitating various scanner setups were evaluated. The in vivo data was also used to validate the optimal variable flip angle combination derived from simulations. Bundle-specific profiles of MCR-MWI derived microstructural parameters were investigated, as well as the cross-correlations of those parameters. Good cross-session repeatability is observed for MCR-MWI. While good correlations can also be found in myelin water fraction (MWF) across protocols, systematic differences, particularly for protocols with different repetition times, are observed. Numerical simulations indicate that MCR-MWI can be performed with a minimum of three flip angles covering a wide range of T1 weighting without adding significant measurement bias and the result is supported by the in vivo experiment allowing whole brain 1.5mm isotropic MWF maps to be acquired in 9 minutes. Bundles-specific MWF analysis reveals that certain white matter bundles are similar in all three participants. We also found that microstructure relaxation parameters have low correlations with MWF. MCR-MWI is a reproducible measure of myelin. However, attention should be paid to considering the protocol related MWF differences for comparison studies, especially when different repetition times are used as this can introduce biases up to 0.5% of MWF in our tested protocols. The optimised flip angle acquisition scheme can reduce the total scan time to 40% of the original implementation without significant quality degradation.

Highlights

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Multi-compartment relaxometry based myelin water imaging (MCR-MWI) can be performed with data comprising as few as 3 flip angles without introducing substantial bias or instability in the fitting procedure;

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MCR-MWI is a reproducible measure of myelin water fraction (MWF) and incorporating DWI can further improve the measurement reproducibility;

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MCR-MWI allows the acquisition of whole brain 1.5mm isotropic MWF maps in 9 minutes, even without the use of advanced model-based reconstructions;

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Small MWF bias can present in cross-protocol comparison if the MT effect is not constant across GRE protocols (e.g., different TRs or flip angle combinations);

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Compartmental relaxation parameters derived from MCR-MWI possess complimentary information beyond myelin water concentration.