bluuebunny/crossref_metadata_2025 huggingface dataset:
Periprosthetic fracture management: global approaches
Authors: Miclau Theodore
Published: March 2023

The incidence of periprosthetic fractures (PPFs) continues to increase worldwide. The goal of management is to restore mobility early while minimizing potential treatment complications. The general medical frailty of patients sustaining PPFs complicates the management of these conditions, with many of those affected being highly susceptible to the consequences of impaired mobilization. Outcomes depend on patient-related (eg, age, physiological condition, medical comorbidities, quality of bone, presence of osteolysis, previous procedures, sex) and surgeon-related (eg, diagnosis, choice of procedure, selected implant, and surgical technique) factors, and preventative measures to decrease the risk of PPFs should be pursued whenever possible. The articles in this supplement address the treatment of the most commonly encountered PPFs, specifically those in the proximal humerus, acetabulum, proximal femur, distal femur, and proximal tibia. This work represents a collaborative effort of the member societies of the International Orthopaedic Trauma Association, an international association of orthopaedic organizations dedicated to the promotion of musculoskeletal trauma care through advancements in patient care, research, and education. The expectation is that the information provided in this supplement will improve the care of patients with PPFs.
The Epidemiology and Costs of Disease Intervention Specialist Retention
Authors: Becher Julie , Salmon Melinda E. , Gift Thomas L.
Published: March 2023

Introduction

The COVID-19 pandemic changed the environment in which disease intervention specialists (DIS) operate, as their skills were in demand beyond STD control programs. Workforce conditions generally have changed in the last 2 years, imposing additional challenges. Retaining STD DIS has become more difficult in the changed environment.

Materials and Methods

We conducted a landscape scan and obtained data from literature and personal observations to characterize current DIS workforce issues. We used published employment data to characterize current labor market conditions and described how cost-effectiveness analysis could be used to assess potential DIS retention interventions. An example illustrating cost-effectiveness concepts was developed.

Results

Many STD control programs faced difficulties in retaining STD DIS, because competing positions often could be done without field work. Economic and crime issues posed additional challenges. General workforce turnover has increased 33% since 2016. Turnover varies by age, gender, and education. Cost-effectiveness analysis can be used to assess DIS retention interventions, but data on costs and outcomes are needed on an ongoing basis. Changes in the workforce environment could impact both retention and the effectiveness of retention interventions.

Conclusions

Workforce changes have impacted employee retention. Increased federal funding makes expansion of the DIS workforce possible, but the labor market environment will continue to pose challenges to recruitment and retention.
Safety and Efficacy of 68Ga- or 177Lu-Labeled DOTA-IBA as a Novel Theranostic Radiopharmaceutical for Bone Metastases
Authors: Qiu Lin , Wang Yingwei , Liu Hanxiang , Wang Qixin , Chen Lin , Liu Lin , Wang Li , Feng Yue , Chen Yue
Published: March 2023

Purpose

We designed and synthesized a novel theranostic bisphosphonate radiopharmaceutical (68Ga- or 177Lu-labeled DOTA-ibandronic acid [68Ga/177Lu-DOTA-IBA]) for bone metastasis. In this study, the dosimetry, safety, and efficacy of 68Ga/177Lu-DOTA-IBA as a theranostic radiopharmaceutical for bone metastases were evaluated in patients with malignancy based on 68Ga- and 177Lu-DOTA-IBA images, blood samples, and dosimetric analysis.

Patients and Methods

Eighteen patients with bone metastasis and progression under conventional therapies were included in this study. Baseline 99mTc-MDP SPECT and 68Ga-DOTA-IBA PET/CT were performed for comparative purposes within 3 days. After receiving 891.5 ± 301.3 MBq 177Lu-DOTA-IBA, serial 177Lu-DOTA-IBA SPECT bone scan was performed over 14 days. Dosimetric evaluation was performed for main organs and tumor lesions. Safety was assessed by blood biomarkers. Karnofsky Performance Status, pain score, and follow-up 68Ga-DOTA-IBA PET/CT were performed for response evaluation.

Results

Baseline 68Ga-DOTA-IBA PET demonstrated a higher efficacy for detecting bone metastases compared with 99mTc-MDP SPECT. The time-activity curves showed fast uptake and high retention of 177Lu-DOTA-IBA in bone metastases (24 hours: 9.43 ± 2.75 %IA; 14 days: 5.45 ± 2.52 %IA). Liver, kidneys, and red marrow time-activity curves revealed a low uptake and fast clearance. The radiation-absorbed dose in bone metastasis lesions (6.40 ± 2.13 Gy/GBq) was significantly higher than that in red marrow (0.47 ± 0.19 Gy/GBq), kidneys (0.56 ± 0.19 Gy/GBq), or liver (0.28 ± 0.07 Gy/GBq), with all P’s < 0.001. Compared with baseline level, only one patient developed new grade 1 leukopenia (toxicity rate, 6%). The 177Lu-DOTA-IBA therapy had no statistically significant effect on bone marrow hematopoietic function, liver function, and kidney function at any follow-up visit. Bone pain palliation was achieved in 82% (14/17) of patients. The 8-week follow-up 68Ga-DOTA-IBA PET/CT demonstrated partial response in 3 patients, disease progression in 1 patient, and stable disease in 14 patients.

Conclusions

68Ga/177Lu-DOTA-IBA provides a set of potential theranostic radiopharmaceuticals and may have a good prospect for the management of bone metastasis.
Orbital Foraminal Morphometrics in Nonsyndromic Unilateral Coronal Craniosynostosis
Authors: Liu Helen , Katz Abigail , Janssen Pierce , Rajasekaran Vignesh , Stanton Eloise , Oleru Olachi O. , Bellaire Christopher P. , Devarajan Alex , Napoli James G. , Rutland John W. , Lacoste Joshua , Frempong Tamiesha , Delman Bradley N. , Urata Mark M. , Taub Peter J.
Published: March 2023

Nonsyndromic unilateral coronal craniosynostosis (UCS) is a rare congenital disorder that results from premature fusion of either coronal suture. The result is growth restriction across the suture, between the ipsilateral frontal and parietal bones, leading to bony dysmorphogenesis affecting the calvarium, orbit, and skull base. Prior studies have reported associations between UCS and visual abnormalities. The present study utilizes a novel geometric morphometric analysis to compare dimensions of orbital foramina on synostotic versus nonsynostotic sides in patients with UCS. Computed tomography head scans of pediatric UCS patients were converted into 3-dimensional mesh models. Anatomical borders of left and right orbital structures were plotted by a single trained team member. Dimensions between synostotic and nonsynostotic sides were measured and compared. Medical records were examined to determine prevalence of visual abnormalities in this patient cohort. Visual abnormalities were reported in 22 of the 27 UCS patients (77.8%). Astigmatism (66.7%), anisometropic amblyopia (44.4%), and motor nerve palsies (33.3%) represented the 3 most prevalent ophthalmologic abnormalities. Orbits on synostotic sides were 11.3% narrower (P < 0.001) with 21.2% less volume (P = 0.028) than orbits on nonsynostotic sides. However, average widths, circumferences, and areas were similar between synostotic and nonsynostotic sides upon comparison of supraorbital foramina, infraorbital foramina, optic foramina, and foramina ovalia. Therefore, previously proposed compression or distortion of vital neurovascular structures within bony orbital foramina does not seem to be a likely etiology of visual abnormalities in UCS patients. Future studies will examine the role of ocular and/or neuro-ophthalmologic pathology in this disease process.
Comparison of Tumescent Anesthesia Versus Pectoral Nerve Block in Bilateral Reduction Mammaplasty
Authors: McLaughlin Caroline M. , Hughes Alexa J. , Lee Charles C. , Perez Holguin Rolfy A. , Warfield Dennis J. , Henry Cathy R. , Johnson Timothy S. , Potochny John D.
Published: March 2023

Introduction

With an increasing focus on multimodal pain control to reduce opioid requirements, regional and local anesthesia techniques have been investigated in bilateral reduction mammaplasty with variable results. The purpose of this study is to compare tumescent anesthesia with pectoral nerve block II (PECS II) in patients undergoing bilateral reduction mammaplasty with respect to postoperative pain and nausea, opioid consumption, length of stay, and cost.

Methods

A retrospective review of patients undergoing bilateral reduction mammaplasty for macromastia between November 2020 and December 2021 was performed. Demographic information, operative and anesthesia times, antiemetic and morphine equivalent requirements, postoperative numeric pain rating scales, and time until hospital discharge were compared between groups.χ2and Fisher exact tests examined subgroup differences in categorical variables. Two-samplettest and Wilcoxon rank-sum test evaluated differences in continuous parametric and nonparametric variables, respectively.

Results

Fifty-three patients underwent bilateral reduction mammaplasty by 3 surgeons, 71.7% (n = 38) with tumescent anesthesia infiltrated by the operating surgeon before the start of the procedure and 28.3% (n = 15) with bilateral PECS II blocks performed by anesthesia before the start of the procedure. There was no difference in age, body mass index, weight resected, intraoperative medication, or immediate postoperative complications. Postoperative pain scores and opioid requirements were similar between the 2 groups. Twenty-one percent (n = 8) of tumescent patients compared with 66.7% (n = 10) of block patients required 1 or more doses of postoperative antiemetics (P= 0.002). Patients who received blocks spent longer in the postoperative recovery area (5.3 vs 7.1 hours,P< 0.01). However, this did not translate to a significant increase in overnight stays. The block group had significantly higher hospitalization cost by an average of $4000, driven by pharmacy and procedural cost (P< 0.01).

Conclusion

In this cohort of multimodal perioperative pain-controlled reduction mammaplasty patients, tumescent anesthesia was associated with decreased antiemetic requirements, less time in recovery before discharge, and lower cost compared with PECS II blocks. Therefore, tumescent anesthesia may be favored over PECS II blocks when considering multimodal pain control strategies in reduction mammaplasty patients.
Examination of Outcome Disparities in Reports of Prepectoral and Subpectoral Direct-to-Implant Reconstruction
Authors: Montorfano Lisandro , Hung Ya-Ching , Chaker Sara , Saad Mariam , Kalmar Christopher L. , Ferri Francisco , Higdon Kent K. , Perdikis Galen
Published: March 2023

Background

There are mixed results in surgical complications regarding the usage of prepectoral versus subpectoral implant placement in direct-to-implant breast reconstruction. This study aimed to provide a comprehensive synthesis of surgical complications between the subpectoral and prepectoral reconstructive method.

Methods

PubMed, Embase, and Cochrane were searched for literature published up until December 2022. Studies that compared subpectoral and prepectoral breast reconstruction and reported at least one postoperative complication were included. The following 8 major outcomes were included: revision and reoperation, capsular contracture, explantation, seroma, hematoma, infection, skin necrosis, and animation deformity. Systematic review and meta-analysis were performed to compare outcomes of the 2 techniques. Subgroup analysis was performed to compare whether practice differences in different countries may have an impact on outcomes.

Results

A total of 18 studies were identified in our literature search. Two thousand three hundred sixty patients were included, representing a total of 3135 breasts. Our analysis demonstrated that prepectoral reconstruction had significantly lower odds of developing postoperative hematoma [odds ratio (OR), 0.62; P = 0.05], seroma (OR, 0.67; P = 0.01), infection (OR, 0.64; P = 0.03), revision and reoperation (OR, 0.44; P < 0.00001), and animation deformity (OR, 0.01; P < 0.00001), compared with the subpectoral method. Subgroup analysis showed that differences between 3 countries (United States, Korea, Italy) are low (all subgroup heterogeneity test P > 0.1).

Conclusions

While both subpectoral and prepectoral are safe methods for breast reconstruction, the prepectoral technique may lead to lower odds of developing multiple major postoperative complications.
Viral infectivity in pediatric SARS-CoV-2 clinical samples does not vary by age
Authors: Schmidt Madaline M , Despres Hannah W , Shirley David J , Bose Michael E , McCaul Kate C , Crothers Jessica W , Henrickson Kelly J , Lee Benjamin , Bruce Emily A
Published: March 2023

At the start of the SARS-CoV-2 pandemic, there was much uncertainty about the role of children in infection and transmission dynamics. Through the course of the pandemic, it became clear that children were susceptible to SARS-CoV-2 infection, however they were experiencing a notable lack of severe disease outcomes as compared to the adult population. This trend held true with the emergence of new SARS-CoV-2 variants, even in pediatric populations that were ineligible to be vaccinated. The difference in disease outcomes has prompted questions about the virologic features of SARS-CoV-2 infection in this population. In order to determine if there was any difference in the infectivity of the virus produced by children infected with COVID-19, we compared viral RNA levels (clinical RT-qPCR CTs) and infectious virus titers from 144 SARS-CoV-2 positive clinical samples collected from children ages 0 to 18 years old. We found that age had no impact on the infectiousness of SARS-CoV-2 within our cohort, with children of all ages able to produce high levels of infectious virus.
Multi-omics analysis reveals drivers of loss of β-cell function after newly diagnosed autoimmune type 1 diabetes: An INNODIA‡multicenter study
Authors: Armenteros Jose Juan Almagro , Brorsson Caroline , Johansen Christian Holm , Banasik Karina , Mazzoni Gianluca , Moulder Robert , Hirvonen Karoliina , Suomi Tomi , Rasool Omid , Bruggraber Sylvaine FA , Marcovecchio M Loredana , Hendricks Emile , Al-Sari Naba , Mattila Ismo , Legido-Quigley Cristina , Suvitaival Tommi , Chmura Piotr J , Knip Mikael , Schulte Anke M , Lee Jeong Heon , Sebastiani Guido , Grieco Giuseppina Emanuela , Elo Laura L , Kaur Simranjeet , Pociot Flemming , Dotta Francesco , Tree Tim , Lahesmaa Riitta , Overbergh Lut , Mathieu Chantal , Peakman Mark , Brunak Søren
Published: March 2023

Background

Heterogeneity in the rate of β-cell loss in newly diagnosed type 1 diabetes patients is poorly understood and creates a barrier to designing and interpreting disease-modifying clinical trials. Integrative analyses of complementary multi-omics data obtained after the diagnosis of T1D may provide mechanistic insight into the diverse rates of disease progression.

Methods

We collected samples in a pan-European consortium that enabled the concerted analysis of five different omics modalities in data from 97 newly diagnosed patients. In this study we used Multi-Omics Factor Analysis to identify molecular signatures correlating with post-diagnosis decline in β-cell mass measured as fasting C-peptide.

Results

Two molecular signatures were significantly correlated with fasting C-peptide levels. One signature showed a correlation to neutrophil degranulation, cytokine signaling, lymphoid and non-lymphoid cell interactions and G-protein coupled receptor signaling events that were inversely associated with rapid decline in β-cell function. The second signature was related to translation and viral infection were inversely associated with change in β-cell function. In addition, the immunomics data revealed a Natural Killer cell signature associated with rapid β-cell decline.

Conclusion

Features that differ between individuals with slow and rapid decline in β-cell mass could be valuable in staging and prediction of the rate of disease progression and thus enable smarter (shorter and smaller) trial designs for disease modifying therapies, as well as offering biomarkers of therapeutic effect.

Funding

This work is funded by the Innovative Medicine Initiative 2 Joint Undertaking (IMI2 JU) under grant agreement N° 115797 (INNODIA) and N° 945268 (INNODIA HARVEST). This Joint Undertaking receives support from the Union’s Horizon 2020 research and innovation program and ‘EFPIA’, ‘JDRF’ and ‘The Leona M. and Harry B. Helmsley Charitable Trust’.
The Mediating Role of Systemic Inflammation and Moderating Role of Race/Ethnicity in Racialized Disparities in Incident Dementia: A Decomposition Analysis
Authors: Higgins Tejera César , Ware Erin B. , Hicken Margaret T. , Kobayashi Lindsay C. , Wang Herong , Adkins-Jackson Paris B. , Blostein Freida , Zawistowski Matthew , Mukherjee Bhramar , Bakulski Kelly M.
Published: March 2023

Abstract Description

Background

Exposure to systemic racism is linked to increased dementia burden. To assess systemic inflammation as a potential pathway linking exposure to racism and dementia disparities, we investigated the mediating role of C-reactive protein (CRP), a systemic inflammation marker, and the moderating role of race/ethnicity on racialized disparities in incident dementia.

Methods

In the US Health and Retirement Study (n=5,143), serum CRP was measured at baseline (2006, 2008 waves). Incident dementia was classified by cognitive tests over a six-year follow-up. Self-reported racialized categories were a proxy for exposure to the racialization process. We decomposed racialized disparities in dementia incidence (non-Hispanic Black and/or Hispanic vs. non-Hispanic White) into 1) the mediated effect of CRP, 2) the moderated portion attributable to the interaction between racialized group membership and CRP, and 3) the controlled direct effect (other pathways through which racism operates).

Results

The 6-year cumulative incidence of dementia was 15.5%. Among minoritized participants (i.e., non-Hispanic Black and/or Hispanic), high CRP levels (> 75thpercentile or 4.57μg/mL) was associated with 1.27 (95%CI: 1.01,1.59) times greater risk of incident dementia than low CRP (<4.57μg/mL). Decomposition analysis comparing minoritized versus non-Hispanic White participants showed that the mediating effect of CRP accounted for 2% (95% CI: 0%, 6%) of the racial disparity, while the interaction effect between minoritized group status and high CRP accounted for 12% (95% CI: 2%, 22%) of the disparity. Findings were robust to potential violations of causal mediation assumptions.

Conclusions

Systemic inflammation mediates racialized disparities in incident dementia.
An App-Based Ecological Momentary Assessment of Undergraduate Mental Health During the COVID-19 pandemic in Canada (Smart Healthy Campus Version 2.0): Longitudinal Study
Authors: Brogly Chris , Lizotte Daniel J , Mitchell Marc , Speechley Mark , MacDougall Arlene , Huner Erin , Anderson Kelly K , Bauer Michael A
Published: March 2023

This paper presents results from the Smart Healthy Campus 2.0 study/smartphone app, developed and used to collect mental health-related lifestyle data from 86 Canadian undergraduates January – August 2021. This was a longitudinal repeat measures study conducted over 40 weeks. A 9-item mental health questionnaire was accessible once daily in the app. Two variants of this mental health questionnaire existed; the first was a weekly variant, available each Monday or until a participant responded during the week. The second was a daily variant available after the weekly variant. Mixed models were fit for responses to the two variants and 12 phone digital measures (e.g. GPS, step counts). A second round of models was fit based on backward elimination to determine associations between the 12 digital measures and the variants. 6518 digital measure samples and 1722 questionnaire responses were collected. The daily questionnaire had positive associations with floors walked, installed apps, and campus proximity, while having negative associations with uptime, and daily calendar events. Daily depression had a positive association with uptime. Daily resilience appeared to have a slight positive association with campus proximity. The weekly questionnaire variant had positive associations with device idling and installed apps, and negative associations with floors walked, calendar events, and campus proximity. Physical activity, weekly, had a negative association with uptime, and a positive association with calendar events and device idling. SHC 2.0, via phone digital measures, identified indicators of lifestyle that appeared to be associated with measures of mental health in undergraduates during COVID-19.

Author Summary

This paper analyzes the associations between digital measures from smartphones (such as GPS and step counts) and a broad mental health questionnaire (covering items like depression and anxiety). This data was collected from students at a relatively large, urban university in Canada during the COVID-19 pandemic. We conducted this study because smartphone-based studies observing aspects of mental health in students as they go about their daily lives are uncommon in Canada. Additionally, mental health concerns, such as depression and anxiety, can be common on university campuses, although it isn’t always clear what is associated with those concerns, especially when only looking at them with smartphone data. We were also interested in how an overview of student mental health would relate to digital measures coming from smartphones during the pandemic, as this information would be relevant to inform future pandemics. In general, these relationships might potentially inform ways to improve student mental health, or potentially predict aspects of it, based on data coming in from smartphones.
Inhibition of the beta-1 adrenergic receptor does not potentiate mirabegron-stimulated human brown adipose tissue thermogenesis.
Authors: Dumont Lauralyne , Caron Alexandre , Richard Gabriel , Croteau Etienne , Fortin Melanie , Frisch Frederique , Phoenix Serge , Dubreuil Stephanie , Guerin Brigitte , Turcotte Eric E. , Carpentier Andre C. , Blondin Denis P.
Published: March 2023

Pharmacological stimulation of human brown adipose tissue (BAT) has been hindered by either ineffective activation or undesirable off-target secondary effects. Oral administration of the maximal allowable dose of mirabegron (200 mg), a β3-adrenergic receptor (β3-AR) agonist, has been effective in stimulating BAT thermogenesis and whole-body energy expenditure. However, this too has been accompanied by undesirable cardiovascular effects. Combining mirabegron with a cardio-selective β1-AR antagonist could not only suppress these unwanted effects, but potentially increase the sensitivity of the β3-AR and β2-AR in WAT and BAT. Here we report that co-ingesting a high dose of the β1-AR antagonist bisoprolol with mirabegron suppresses the increase in heart rate, systolic blood pressure and myocardial oxygen consumption. However, it also blunted the mirabegron-stimulated increase in BAT lipolysis, thermogenesis and glucose uptake. Whether the attenuation in BAT blood flow induced by the large dose of bisoprolol limited BAT thermogenesis remains to be determined. Clinical Trial Registration ID #:NCT04823442
Keeping the ‘C’ in CBPR: Exploring Community Researchers’ Experiences with Human Subjects Protection Training Requirements
Authors: Cruz Naomi , Adams Christiana , Akhimien Constance , Abdulkadir Fauziyya Allibay , Battle Cherriece , Oluwayemi Maria , Salimon Olanike , Lassiter Teri , Kantor Leslie
Published: March 2023

Community-engaged research is increasingly recognized for its potential to advance health equity. The ability to conduct such research in the United States is predicated on the completion of human subjects protection courses; however, prior studies suggest that many of these required courses may not adequately accommodate the varied skillsets and backgrounds of community members involved with carrying out research. The present study explores community researchers’ (CRs’) experiences with a widely used human subjects protection course frequently mandated by universities. Six CRs involved in conducting a community-based participatory research (CBPR) project on Black women’s pregnancy-related experiences were interviewed about their completion of a required human subjects protection course. Across multiple interviews, CRs noted challenges with the training length, competing external demands, module readability, content relevancy, end-of-module quizzes, and technology requirements. Despite such obstacles, CRs still valued the opportunity to learn and felt more knowledgeable and capable post-course completion. Recommendations for course improvement were explored. University requirements for human subjects protection trainings may place an undue burden on community members preparing to conduct research, impede academic-community partnerships, and discourage the initiation and continuation of community-engaged studies. Course alternatives that are tailored to CRs are needed.
DWI ASPECTS Can Detect Patients Who Require Puncture to Recanalization within 30 minutes for Large Vessel Occlusion
Authors: Yoshie Tomohide , Ueda Toshihiro , Hasegawa Yasuhiro , Takeuchi Masataka , Morimoto Masafumi , Tsuboi Yoshifumi , Yamamoto Ryoo , Kaku Shogo , Ayabe Junichi , Akiyama Takekazu , Yamamoto Daisuke , Mori Kentaro , Kagami Hiroshi , Ito Hidemichi , Onodera Hidetaka , Kaga Yasuyuki , Ohtsubo Haruki , Tatsuno Kentaro , Usuki Noriko , Takaishi Satoshi , Yamano Yoshihisa
Published: March 2023

Abstracts

BACKGROUND

Faster recanalization for acute large vessel occlusion is associated with better clinical outcome. The aim of this study was to identify patient characteristics that require puncture-to-recanalization (P-R) time within 30 min for good clinical outcome.

METHODS

We evaluated the patients from K-NET Registry, which is a prospective, multicenter, observational registry of acute ischemic stroke patients. The present analysis included patients who met the following criteria: (1) treated with endovascular therapy for ICA or MCA M1 occlusion; and (2) achieved successful recanalization (mTICI 2b or more). Patients were divided into subgroups according to pre-treatment patients’ characteristics; DWI ASPECTS, age, NIHSS, occlusion site and symptom recognition to puncture time. In each subgroup, the frequency of good clinical outcomes was compared between P-R time <30min and >30min. We entered interaction terms into the models to evaluate the correlation between each patient characteristic and P-R time.

RESULTS

1053 patients were included in this study. Overall, P-R <30min was significantly associated with good outcome. Univariate analysis in each subgroup revealed a significant association between P-R <30min and good outcomes in the patients with DWI ASPECTS ≤6, age >85 and NIHSS ≥16. In multivariable analysis, NIHSS, age, symptom recognition to puncture time, DWI ASPECTS and P-R <30 minutes were significant independent predictors of good outcomes; however, only DWI ASPECTS had interaction terms with P-R <30 minutes. Multivariable analysis showed P-R <30min was an independent predictor for good outcome in patients with DWI ASPECTS ≤6, whereas P-R<30min was not in patients with DWI ≥7.

CONCLUSIONS

P-R<30 min is a predictor of good clinical outcome, however, the effect depends on DWI ASPECTS. A target P-R time of less than 30 minutes is appropriate for patients with DWI ASPECTS scores of 0-6, whereas 30 minutes or longer is reasonable for patients with DWI ASPECTS 7 or higher.
Genetic study of psoriasis highlights its close link with socio-economic status and affective symptoms
Authors: Heikkilä Anni , Sliz Eeva , Huilaja Laura , FinnGen  ,   Estonian Biobank Research Team, Reis Kadri , Palta Priit , Elnahas Abdelrahman G. , Reigo Anu , Esko Tõnu , Laisk Triin , Teder-Laving Maris , Tasanen Kaisa , Kettunen Johannes
Published: March 2023

Psoriasis is an inflammatory skin disease with an estimated heritability of around 70 %. Previous genome-wide association studies (GWASs) have detected several risk loci for psoriasis. To further improve the understanding of the genetic risk factors impacting the disease, we conducted a discovery GWAS in FinnGen and a subsequent replication and meta-analysis with data from the Estonian Biobank and the UK biobank; the study sample included 925 649 individuals (22 659 cases and 902 990 controls), the largest sample for psoriasis yet. In addition, we conducted downstream analyses to find out more about psoriasis’ cross-trait genetic correlations and causal relationships. We report 8 novel risk loci, most of which harbor genes related to nuclear factor kappa-light-chain-enhancer of activated B-cells-signaling pathway and overall immunity. Genetic correlations highlight the relationship between psoriasis and smoking, higher body weight, and lower education level. Additionally, we report novel causal relationships between psoriasis and mood symptoms, as well as two-directioned causal relationship between psoriasis and lower education level. Our results provide new knowledge on psoriasis risk factors, which may be useful in the development of future treatment strategies.
A small-scale Development Impact Bond for hepatitis C diagnosis and treatment in Cameroon: the way to elimination?
Authors: Dieteren C.M. , Boers A.C. , Thomas W. , Njoya O. , Coutinho R.A. , Mossus T , Essomb F , Wafeu G , Agnouanang B
Published: March 2023

In the absence of sufficient (tax-based) healthcare financing in low-and middle-income countries, innovative financing models are needed. This study assessed quantitatively and qualitative the feasibility of a Development Impact Bond (DIB) for hepatitis C Virus (HCV) diagnosis and treatment in Cameroon. A revolving fund of up to €230,000 was made available by the investor. The outcome payor repaid the investor only in case of good performance, defined as cured patients (HCV-RNA negative). Identified HCV carriers were referred for treatment and tested for cure 12 weeks after completion of treatment, the outcome being validated by an independent party. The evaluation was guided by a recognized framework, involving interviews with relevant stakeholders (N= 22). In total, 253 (98%) patients completed treatment of which 244 (96%) are cured at week 24. We estimated that the average per patientoutcome paymentfor HCV diagnosis and treatment is €1,542 and theaverage costs per treated patientis €1,858. The investor was fully repaid including the agreed interest and bonus rate. The interviews confirmed the feasibility of the DIB in a low-resource setting. This study demonstrates that a DIB can be a suitable financing mechanism for HCV services, supporting the path towards elimination. When governments do not have sufficient resources to fund such elimination programs upfront, such public-private partnerships can offer a solution.

Highlights

The availability of a short-course highly effective hepatitis C treatment paves the way towards its elimination.

We demonstrate feasibility of the first Development Impact Bond (DIB) as a financing mechanism for hepatitis C diagnosis and treatment.

This study shows that with an average per patient outcome payment of €1,542, one HCV patient can be diagnosed and treated in a lower-middle income country.
Malaria temporal dynamic clustering for surveillance and intervention planning
Authors: Legendre Eva , Lehot Laurent , Dieng Sokhna , Rebaudet Stanislas , Thu Aung Myint , Rae Jade D , Delmas Gilles , Girond Florian , Herbreteau Vincent , Nosten François , Landier Jordi , Gaudart Jean
Published: March 2023

Background

Targeting interventions where most needed and effective is crucial for public health. Malaria control and elimination strategies increasingly rely on stratification to guide surveillance, to allocate vector control campaigns, and to prioritize access to community-based early diagnosis and treatment (EDT). We developed an original approach of dynamic clustering to improve local discrimination between heterogeneous malaria transmission settings.

Methods

We analysed weekly malaria incidence records obtained from community-based EDT (malaria posts) in Karen/Kayin state, Myanmar. We smoothed longitudinal incidence series over multiple seasons using functional transformation. We regrouped village incidence series into clusters using a dynamic time warping clustering and compared them to the standard, 5-category annual incidence standard stratification.

Results

We included 1,115 villages from 2016 to 2020. We identified elevenP. falciparumandP. vivaxincidence clusters which differed by amplitude, trends and seasonality. Specifically the 124 villages classified as “high transmission area” in the standardP. falciparumstratification belonged to the 11 distinct groups when accounting to inter-annual trends and intra-annual variations. Likewise forP. vivax, 399 “high transmission” villages actually corresponded to the 11 distinct dynamics.

Conclusion

Our temporal dynamic clustering methodology is easy to implement and extracts more information than standard malaria stratification. Our method exploits longitudinal surveillance data to distinguish local dynamics, such as increasing inter-annual trends or seasonal differences, providing key information for decision-making. It is relevant to malaria strategies in other settings and to other diseases, especially when many countries deploy health information systems and collect increasing amounts of health outcome data.

Funding

The Bill & Melinda Gates Foundation, The Global Fund against AIDS, Tuberculosis and Malaria (the Regional Artemisinin Initiative) and the Wellcome Trust funded the METF program.
Where, who, and what counts under area-based conservation targets: A framework for identifying opportunities that benefit biodiversity, climate mitigation, and human communities
Authors: Bateman Brooke L , Feng Emily , Grand Joanna , Taylor Lotem , Wu Joanna X , Saunders Sarah P , Wilsey Chad
Published: March 2023

Area-based conservation targets, such as ‘30−30’, if strategically applied, can increase resiliency to climate change and provide co-benefits to people and biodiversity. However, protected areas historically were not designated within the context of global change, and human communities at highest risk are often overlooked in conservation planning.

To inform 30−30 conservation planning in the United States (i.e., America the Beautiful; ATB), we evaluatedwhereUS conservation opportunities exist by identifying habitats that can simultaneously benefit climate change mitigation and bird populations, as well aswholives in these areas and how conservation actions could both improve human well-being or potentially be at odds with local communities. To inform the equitable implementation of area-based conservation targets, we integrated maps of critical habitat for birds now and under a changing climate with carbon stocks and sinks and developed a prioritization framework to investigate the spatial alignment of these locations with areas identified as important for both human well-being and land-dependent human communities.

Although nearly 30% of US lands have some level of protection, only 6% of US lands (143 million acres) are managed for biodiversity and align with Bird and Carbon (BC) priorities, and <3% of protected US lands (59 million acres) align with priorities for Birds, Carbon, and Human well-being (BCH).

Of the 312 million acres of BCH priorities identified, 71% lack known protection or formal conservation plans (14% of US lands) and should be considered conservation opportunities that could simultaneously address the biodiversity and climate crises, and social inequities. Targeting these BCH areas for conservation action would contribute to more equitable benefits to marginalized communities, and could fulfill the ‘Justice 40’ commitment, which aims to allocate 40% of federal investments in climate benefits to marginalized communities (which, for the 30% goal under ATB equates to 12% of US lands).

At least 80% of all BCH priorities co-occur with Indigenous peoples and local communities (IPLCs) who have strong cultural and socioeconomic ties to the land, making it imperative to work with local communities to definewhat countsas conservation actions towards the 30% goal and what successful conservation outcomes that benefit biodiversity, climate change mitigation, and human communities look like.
Diagnostic Performance of MRI Radiomics for Classification of Alzheimer’s disease, Mild Cognitive Impairment, and Normal Subjects: A Systematic Review and Meta-analysis
Authors: Shahidi Ramin , Baradaran Mansoureh , Asgarzadeh Ali , Bagherieh Sara , Tajabadi Zohreh , Farhadi Akram , Korani Setayesh Sotoudehnia , Khalafi Mohammad , Shobeiri Parnian , Sadeghsalehi Hamidreza , Shafieyoun Arezoo , Yazdanifar Mohammad Amin , Singhal Aparna , Sotoudeh Houman
Published: March 2023

Background

Alzheimer’s disease (AD) is a debilitating neurodegenerative disease. Early diagnosis of AD and its precursor, mild cognitive impairment (MCI), is crucial for timely intervention and management. Magnetic resonance imaging (MRI) radiomics showed a promising result for diagnosing and classifying AD, and MCI from normal subjects. Thus, we aimed to systematically evaluate the diagnostic performance of the MRI radiomics for this task.

Methods and materials

A comprehensive search of the current literature was conducted using relevant keywords in PubMed/MEDLINE, Embase, Scopus, and Web of Science databases from inception to October 17, 2022. Original studies discussing the diagnostic performance of MRI Radiomics for the classification of AD, MCI, and normal subjects were included. Method quality was evaluated with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2), and the Radiomic Quality Score tool (RQS).

Results

We identified 10 studies that met the inclusion criteria, involving a total of 3446 participants. The overall quality of the included studies was moderate to high. The pooled sensitivity and specificity of MRI radiomics for differentiating AD from normal subjects were 0.8822 (95% CI 0.7888-0.9376), and 0.8849 (95% CI 0.7978-0.9374), respectively. The pooled sensitivity and specificity of MRI radiomics for differentiating MCI from normal subjects were 0.7882 (95% CI 0.6272-0.8917) and 0.7736 (95% CI 0.6480-0.8639), respectively. Also, the pooled sensitivity and specificity of MRI radiomics for differentiating AD from MCI were 0.6938 (95% CI 0.6465-0.7374) and 0.8173 (95% CI 0.6117-0.9270), respectively.

Conclusion

MRI radiomics has promising diagnostic performance in differentiating AD, MCI, and normal subjects. It can potentially serve as a non-invasive and reliable tool for early diagnosis and classification of AD and MCI.
Dark citations to Federal resources and their contribution to the public health literature
Authors: Keralis Jessica M. , Albertorio-Díaz Juan , Hoppe Travis
Published: March 2023

The term “dark citations”, which has been previously used to refer to citations of information products outside of traditional peer-reviewed journal articles, is adapted here to refer to those that are not linked to a known indexed identifier and are effectively invisible to traditional bibliometric analysis. We investigate an unexplored source of citations in the biomedical and public health literature by surveying the extent of dark citations across the U.S. government. We systematically focus on public health, quantify their occurrences across the government, and provide a comprehensive dataset for all dark citations within PubMed.
ScRNA-seq of Diverse Pheochromocytoma Patients Reveals Distinct Microenvironment Characteristics and Supports an Informative Molecular Classification System
Authors: Qin Sen , Xu Yawei , Yu Shimiao , Han Wencong , Fan Shiheng , Ai Wenxiang , Zhang Kenan , Wang Yizhou , Zhou Xuehong , Shen Qi , Gong Kan , Sun Luyang , Zhang Zheng
Published: March 2023

Pheochromocytomas (PCCs) are rare neuroendocrine tumors that originate from chromaffin cells in the adrenal gland. However, the cellular molecular characteristics and immune microenvironment of PCCs are incompletely understood. Here, we performed single-cell RNA sequencing (scRNA-seq) on 16 tissues from 4 sporadic unclassified PCC patients and 1 hereditary PCC patient with Von Hippel-Lindau (VHL) syndrome. We found that intra-tumoral heterogeneity was less extensive than the inter-individual heterogeneity of PCCs. Further, the unclassified PCC patients were divided into two types, metabolism-type (marked by NDUFA4L2 and COX4I2) and kinase-type (marked by RET and PNMT), validated by immunohistochemical staining. Trajectory analysis of tumor evolution revealed that metabolism-type PCC cells display phenotype of consistently active metabolism and increased metastasis potential, while kinase-type PCC cells showed decreased epinephrine synthesis and neuron-like phenotypes. Cell-cell communication analysis showed activation of the annexin pathway and a strong inflammation reaction in metabolism-type PCCs and activation of FGF signaling in the kinase-type PCC. Although multispectral immunofluorescence staining showed a lack of CD8+T cell infiltration in both metabolism-type and kinase-type PCCs, only the kinase-type PCC exhibited downregulation ofHLA-Imolecules that possibly regulated byRET, suggesting the potential of combined therapy with kinase inhibitors and immunotherapy for kinase-type PCCs; in contrast, the application of immunotherapy to metabolism-type PCCs (with antigen presentation ability) is likely unsuitable. Our study presents a single-cell transcriptomics-based molecular classification and microenvironment characterization of PCCs, providing clues for potential therapeutic strategies to treat PCCs.
Structural modification of naturally-occurring phenolics as a strategy for developing cytotoxic molecules towards cancer cells
Authors: Olim Pedro , Pereira Renato B. , Fernandes Maria José G. , Natal Carolina M. , Coelho José R. A. , Fortes A. Gil , Sameiro M. , Gonçalves T. , Pereira David M.
Published: March 2023

Natural products belonging to different chemical classes have been established as a promising source of novel anticancer drugs. Several low molecular weight compounds from the classes of monoterpenes, phenylpropanoids and flavonoids were shown to possess anticancer activities in previous studies. In this work, over 20 semisynthetic derivatives of molecules belonging to these classes, namely thymol, eugenol and 6-hydroxyflavanone were synthesized and tested for their cytotoxicity against two human cancer cell lines, namely gastric adenocarcinoma (AGS cells) and human lung carcinoma (A549 cells). An initial screening based on viability assessment was performed in order to identify the most cytotoxic compounds at 100 μM. The results evidenced that two 6-hydroxyflavanone derivatives were the most cytotoxic among the compounds tested, being selected for further studies. Noteworthy, in a general way some of the derivatives synthesized displayed enhanced toxicity when compared with their natural counterparts. Moreover, LDH assay showed that the loss of cell viability was not accompanied by a loss of membrane integrity, thus ruling out a necrotic process. Morphological studies with AGS cells demonstrated chromatin condensation compatible with apoptosis, confirmed by the activation of caspase 3/7. Furthermore, a viability assay on non-cancer human embryonic lung fibroblast cell line (MRC-5) confirmed these two derivatives possess selective anticancer activity.
Design of anArabidopsis thalianareporter line to detect heat-sensing and signaling mutants
Authors: Guihur Anthony , Bourgine Baptiste , Rebeaud Mathieu E. , Goloubinoff Pierre
Published: March 2023

Background

Global warming is a major challenge for plant survival and growth. Understanding the molecular mechanisms by which higher plants sense and adapt to upsurges in the ambient temperature, is essential for developing strategies to enhance plant tolerance to heat stress. Here, we designed a special heat-responsiveArabidopsis thalianareporter line that allowed an in-depth investigation of the mechanisms underlying the accumulation of protective heat-shock proteins (HSPs) in response to high temperature.

Methods

A transgenicArabidopsis thalianareporter line named “Heat-Inducible Bioluminescence And Toxicity” (HIBAT) was designed to express from a conditional heat-inducible promoter, a fusion gene encoding for nanoluciferase and D-amino acid oxidase, whose expression was found to be toxic only in the presence of D-valine. HIBAT seedlings were exposed to different heat treatments in presence or absence of D-valine and analyzed for survival rate, bioluminescence and HSP gene expression.

Results

Whereas at 22°C, HIBAT seedlings grew unaffected by D-valine, and all survived following iterative heat treatments without D-valine, 98% died following heat treatments on D-valine. The HSP17.3B promoter was highly specific to heat, as it remained unresponsive to various plant hormones, Flagellin, H2O2, osmotic stress and high salt. Confirming that HIBAT does not significantly differ from its Col-0 parent, RNAseq analysis of heat-treated seedlings showed a strong correlation between the two lines. Using HIBAT, a forward genetic screen revealed candidate loss-of-function mutants defective either at accumulating HSPs at high temperature or at repressing HSP accumulation at low, non-heat-shock temperatures.

Conclusion

This study adds insights into the molecular mechanisms by which higher plants sense and adapt to rapid elevations of ambient temperatures. HIBAT was a valuable tool to identifyArabidopsismutants defective in the response to high temperature stress. Our findings open new avenues for future research on the regulation of HSP expression and understanding their role in the onset of plant acquired thermotolerance.
Thymidine kinase-independent click chemistry DNADetect™ probes for DNA proliferation assessment in malaria parasites
Authors: Hilko David H. , Fisher Gillian M. , Addison Russell S. , Andrews Katherine T. , Poulsen Sally-Ann
Published: March 2023

Metabolic chemical probes are small molecule reagents that utilise naturally occurring biosynthetic enzymes forin situincorporation into biomolecules of interest. These reagents can be used to label, detect, and track important biological processes within living cells including protein synthesis, protein glycosylation and nucleic acid proliferation. A limitation of current chemical probes, which have largely focused on mammalian cells, is that they often cannot be applied to other organisms due to metabolic differences. For example, the thymidine derivative 5-ethynyl-2’-deoxyuridine (EdU) is a gold standard metabolic chemical probe for assessing DNA proliferation in mammalian cells however is unsuitable for the study of malaria parasites due toPlasmodiumspecies lacking the thymidine kinase enzyme that is essential for metabolism of EdU. Herein we report the design and synthesis of new thymidine-based probes that sidestep the requirement for a thymidine kinase enzyme inPlasmodium. Two of these DNADetect™ probes exhibit robust labelling of replicating asexual intraerythrocyticP. falciparumparasites, as determined by flow cytometry using copper catalysed azide-alkyne cycloaddition (CuAAC) to a fluorescent azide. The DNADetect™ chemical probes are synthetically accessible and thus can be made widely available to researchers as tools to further understand the biology of differentPlasmodiumspecies, including laboratory lines and clinical isolates.