bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonparametric receiver operating characteristic curve analysis with an imperfect gold standard
Authors: Sun Jiarui , Tang Chao , Xie Wuxiang , Zhou Xiao-Hua
Published: July 2024

This article addresses the challenge of estimating receiver operating characteristic (ROC) curves and the areas under these curves (AUC) in the context of an imperfect gold standard, a common issue in diagnostic accuracy studies. We delve into the nonparametric identification and estimation of ROC curves and AUCs when the reference standard for disease status is prone to error. Our approach hinges on the known or estimable accuracy of this imperfect reference standard and the conditional independent assumption, under which we demonstrate the identifiability of ROC curves and propose a nonparametric estimation method. In cases where the accuracy of the imperfect reference standard remains unknown, we establish that while ROC curves are unidentifiable, the sign of the difference between two AUCs is identifiable. This insight leads us to develop a hypothesis-testing method for assessing the relative superiority of AUCs. Compared to the existing methods, the proposed methods are nonparametric so that they do not rely on the parametric model assumptions. In addition, they are applicable to both the ROC/AUC analysis of continuous biomarkers and the AUC analysis of ordinal biomarkers. Our theoretical results and simulation studies validate the proposed methods, which we further illustrate through application in two real-world diagnostic studies.
Prediction of melanoma metastasis using dermatoscopy deep features: an international multicentre cohort study
Authors: Lallas Konstantinos , Spyridonos Panagiota , Kittler Harald , Tschandl Philipp , Liopyris Konstantinos , Argenziano Giuseppe , Bakos Renato , Braun Ralph , Cabo Horacio , Dika Emi , Malvehy Josep , Marghoob Ash , Puig Susana , Scope Alon , Stolz Wilhelm , Tanaka Masaru , Thomas Luc , Apalla Zoe , Vakirlis Efstratios , Zalaudek Iris , Lallas Aimilios
Published: July 2024

Whether dermatoscopy deep features could serve as biomarker for the prediction of melanoma metastasis remains an underexplored area in medical research. In this cohort of 712 patients from 10 centres in 3 continents, a support vector machine classifier that analysed deep features on dermatoscopic images demonstrated similar prognostic performance for metastasis in terms of AUC and true positive rate to current benchmarks of melanoma staging, namely Breslow thickness and ulceration. Deep features derived from dermatoscopy could predict early-stage melanomas with high metastatic potential, tailoring further treatment strategies.
Artificial intelligence-driven radiomics: developing valuable radiomics signatures with the use of artificial intelligence
Authors: Vrettos Konstantinos , Triantafyllou Matthaios , Marias Kostas , Karantanas Apostolos H , Klontzas Michail E
Published: July 2024

The advent of radiomics has revolutionized medical image analysis, affording the extraction of high dimensional quantitative data for the detailed examination of normal and abnormal tissues. Artificial intelligence (AI) can be used for the enhancement of a series of steps in the radiomics pipeline, from image acquisition and preprocessing, to segmentation, feature extraction, feature selection, and model development. The aim of this review is to present the most used AI methods for radiomics analysis, explaining the advantages and limitations of the methods. Some of the most prominent AI architectures mentioned in this review include Boruta, random forests, gradient boosting, generative adversarial networks, convolutional neural networks, and transformers. Employing these models in the process of radiomics analysis can significantly enhance the quality and effectiveness of the analysis, while addressing several limitations that can reduce the quality of predictions. Addressing these limitations can enable high quality clinical decisions and wider clinical adoption. Importantly, this review will aim to highlight how AI can assist radiomics in overcoming major bottlenecks in clinical implementation, ultimately improving the translation potential of the method.
Healthcare Seeking Behavior and Disease Perception Toward Cholera and Acute Diarrhea Among Populations Living in Cholera High-Priority Hotspots in Shashemene, Ethiopia
Authors: Getahun Tomas , Hailu Dejene , Mogeni Ondari D , Mesfin Getachew Edlawit , Yeshitela Biruk , Jeon Yeonji , Gedefaw Abel , Ayele Abebe Samuyel , Hundito Ermiyas , Mukasa David , Jang Geun Hyeog , Pak Gi Deok , Kim Deok Ryun , Worku Demlie Yeshambel , Hussen Mukemil , Teferi Mekonnen , Park Se Eun
Published: July 2024

Background

Healthcare seeking behavior (HSB) and community perception on cholera can influence its management. We conducted a cross-sectional survey to generate evidence on cholera associated HSB and disease perception in populations living in cholera hotspots in Ethiopia.

Methods

A total of 870 randomly selected households (HHs) in Shashemene Town (ST) and Shashemene Woreda (SW) participated in our survey in January 2022.

Results

Predominant HHs (91.0%; 792/870) responded “primary health center” as the nearest healthcare facility (HCF). Around 57.4% (247/430) of ST HHs traveled <30 minutes to the nearest HCF. In SW, 60.2% (265/440) of HHs travelled over 30 minutes and 25.9% (114/440) over 4 km. Two-thirds of all HHs paid <USD1 travel cost; SW residents had slightly higher cost burden. When cholera symptoms occur, 68.0% (83/122), 75.5% (114/151), 100.0% (52/52), and 100.0% (426/426) of 0–4, 5–14, 15–17, and ≥18 years, respectively, in ST sought healthcare at our sentinel-HCFs. In SW, younger children visited our sentinel-HCFs slightly more (82.6%, 86.7% in 1–4, 5–14 years, respectively) than older age groups (74.4%, 75.6% in 15–17, ≥ 18 years, respectively). Relatively more adults in ST (12.0%; 51/426) sought over-the-counter drugs at pharmacies than those in SW (2.5%; 11/435). Around 73.8% (642/870) of HHs were aware of cholera disease and 66.7% (428/642) of HHs considered eating unclean food as main causes of cholera.

Conclusions

Variations in cholera prevention practices between rural and urban residents were shown. Addressing differences in HSB per age groups is needed for community engagement for early case detection and case management; critical in reducing cholera deaths and transmission.
Coverage of Two-Dose Preemptive Cholera Mass Vaccination Campaign in High-Priority Hotspots in Shashemene, Oromia Region, Ethiopia
Authors: Park Se Eun , Gedefaw Abel , Hailu Dejene , Jeon Yeonji , Mogeni Ondari D , Jang Geun Hyeog , Mukasa David , Mraidi Ramzi , Kim Deok Ryun , Getahun Tomas , Mesfin Getachew Edlawit , Yeshitela Biruk , Ayele Abebe Samuyel , Hussen Mukemil , Worku Demlie Yeshambel , Teferi Mekonnen
Published: July 2024

Background

Cholera is a public health priority in Ethiopia. The Ethiopian National Cholera Plan elaborates a multi-year scheme of oral cholera vaccine (OCV) use. Aligned with this, a preemptive OCV campaign was conducted under our Ethiopia Cholera Control and Prevention project. Here, we present the OCV vaccination outcomes.

Method

Cholera high-priority hotspots in the Oromia Region, Shashemene Town (ST) and Shashemene Woreda (SW), were selected. Four kebelles (Abosto, Alelu, Arada, and Awasho) in ST and 4 clusters (Faji Gole, Harabate, Toga, and Chabi) in SW were study sites with OCV areas nested within. A total of 40 000 and 60 000 people in ST and SW, respectively, were targeted for a 2-dose OCV (Euvichol-Plus) campaign in 11–15 May (first round [R1]) and 27–31 May (second round [R2]) 2022. Daily administrative OCV coverage and a coverage survey in 277 randomly selected households were conducted.

Results

The administrative OCV coverage was high: 102.0% for R1 and 100.5% for R2 in ST and 99.1% (R1) and 100.0% (R1) in SW. The coverage survey showed 78.0% (95% confidence interval [CI]: 73.1–82.9) of household members with 2-dose OCV and 16.8% (95% CI: 12.4–21.3) with no OCV in ST; and 83.1% (95% CI: 79.6–86.5) with 2-dose OCV and 11.8% (95% CI: 8.8–14.8) with no OCV in SW. The 2-dose coverages in 1–4-, 5–14-, and ≥15-year age groups were 88.3% (95% CI: 70.6–96.1), 88.9% (95% CI: 82.1–95.7), and 71.3% (95% CI: 64.2–78.3), respectively, in ST and 78.2% (95% CI: 68.8–87.7), 91.0% (95% CI: 86.6–95.3), and 78.7% (95% CI: 73.2–84.1) in SW.

Conclusions

High 2-dose OCV coverage was achieved. Cholera surveillance is needed to assess the vaccine impact and effectiveness.
Retrospective Analysis of Cholera/Acute Watery Diarrhea Outbreaks in Ethiopia From 2001 To 2023: Incidence, Case Fatality Rate, and Seasonal and Multiyear Epidemic Patterns
Authors: Worku Demlie Yeshambel , Gedefaw Abel , Jeon Yeonji , Hailu Dejene , Getahun Tomas , Mogeni Ondari D , Mukasa David , Jang Geun Hyeog , Pak Gi Deok , Kim Deok Ryun , Getachew Edlawit Mesfin , Yeshitela Biruk , Ayele Abebe Samuyel , Edosa Moti , Wossen Mesfin , Teferi Mekonnen , Park Se Eun
Published: July 2024

Background

The Ethiopian government has developed the multisectoral cholera elimination plan (NCP) with an aim of reducing cholera incidence and case fatality rate (CFR). To better understand and monitor the progress of this plan, a comprehensive review of national cholera epidemiology is needed.

Methods

Reported data on cholera/acute watery diarrhea (AWD) cases in the past 20 years were extracted from the Ethiopian Public Health Institute and World Health Organization databases. Descriptive statistics, Pearson χ2, and logistic regression analyses were conducted.

Results

From January 2001 to November 2023, a total of 215 205 cholera/AWD cases, 2355 deaths with a cumulative CFR of 1.10% (95% confidence interval [CI], 1.092–1.095), and a mean annual incidence rate of 8.9/100 000 (95% CI, 6.5–11.3) were reported. Two major upsurges of cholera epidemics were found in the last two decades with mean attack rate (AR) of 20.57/100 000 in 2006–2010 and 14.83/100 000 in 2016–2020. Another resurgence of outbreaks occured in 2021–2023 (mean AR, 8.63/100 000). In 2015–2023, 54.0% (53 990/99 945) of cases were aged 15–44 years. National cholera CFR (3.13% [95% CI: 2.1–4.5]) was the highest in 2022. The 2015–2023 cumulative cholera CFR was different across regions: Benishangul Gumuz (6.07%), Gambela (1.89%), Sidama (1.42%), Southern Nation, Nationalities, and Peoples’ (1.34%), Oromia (1.10%), and Amhara (1.09%). Cholera/AWD patients in older adults (≥45 years), severe dehydration, peak rainy season (June–August), and outpatients were associated with higher risk of death.

Conclusions

Cholera has been a public health problem in Ethiopia with case fatalities still above the global target. Case management needs to be improved particularly in outpatients and older populations. Outbreak preparedness should be rolled out well in advance of the typical rainy seasons. Significant investments are essential to advance the cholera surveillance system at healthcare setting and community level. Underlying factors of cholera deaths per areas should be further investigated to guide appropriate interventions to meet the NCP target by 2028.
Immunogenicity, Safety, and Efficacy of a Tetravalent Dengue Vaccine in Children and Adolescents: An Analysis by Age Group
Authors: Borja-Tabora Charissa , Fernando LakKumar , Lopez Medina Eduardo , Reynales Humberto , Rivera Luis , Saez-Llorens Xavier , Sirivichayakul Chukiat , Yu Delia , Folschweiller Nicolas , Moss Kelley J , Rauscher Martina , Tricou Vianney , Zhao Yuan , Biswal Shibadas
Published: July 2024

Background

Dengue is an increasing threat to global health. This exploratory analysis evaluated the immunogenicity, safety, and vaccine efficacy (VE) of a live-attenuated tetravalent dengue vaccine (TAK-003) in participants enrolled in the phase 3 DEN-301 trial (NCT02747927), stratified by baseline age (4–5 years, 6–11 years, or 12–16 years).

Methods

Participants were randomized 2:1 to receive 2 doses of TAK-003, administered 3 months apart, or placebo. Dengue serostatus was evaluated at enrolment. VE against virologically confirmed dengue (VCD) and hospitalized VCD; immunogenicity (geometric mean titers [GMTs]); and safety were evaluated per age group through ∼4 years postvaccination.

Results

VE against VCD across serotypes was 43.5% (95% confidence interval [CI]: 25.3%, 57.3%) for 4–5 year-olds; 63.5% (95% CI: 56.9%, 69.1%) for 6–11 year-olds, and 67.7% (95% CI: 57.8%, 75.2%) for 12–16 year-olds. VE against hospitalized VCD was 63.8% (95% CI: 21.1%, 83.4%), 85.1% (95% CI: 77.1%, 90.3%), and 89.7% (95% CI: 77.9%, 95.2%), for the 3 age groups, respectively. GMTs remained elevated against all 4 serotypes for ∼4 years postvaccination, with no evident differences across age groups. No clear differences in safety by age were identified.

Conclusions

This exploratory analysis shows TAK-003 was efficacious in dengue prevention across age groups in children and adolescents 4–16 years of age living in dengue endemic areas. Relatively lower VE in 4–5 year-olds was potentially confounded by causative serotype distribution, small sample size, and VE by serotype, and should be considered in benefit-risk evaluations in this age group.
DrugRepoBank: a comprehensive database and discovery platform for accelerating drug repositioning
Authors: Huang Yixian , Dong Danhong , Zhang Wenyang , Wang Ruiting , Lin Yang-Chi-Dung , Zuo Huali , Huang Hsi-Yuan , Huang Hsien-Da
Published: July 2024

In recent years, drug repositioning has emerged as a promising alternative to the time-consuming, expensive and risky process of developing new drugs for diseases. However, the current database for drug repositioning faces several issues, including insufficient data volume, restricted data types, algorithm inaccuracies resulting from the neglect of multidimensional or heterogeneous data, a lack of systematic organization of literature data associated with drug repositioning, limited analytical capabilities and user-unfriendly webpage interfaces. Hence, we have established the first all-encompassing database called DrugRepoBank, consisting of two main modules: the ‘Literature’ module and the ‘Prediction’ module. The ‘Literature’ module serves as the largest repository of literature-supported drug repositioning data with experimental evidence, encompassing 169 repositioned drugs from 134 articles from 1 January 2000 to 1 July 2023. The ‘Prediction’ module employs 18 efficient algorithms, including similarity-based, artificial-intelligence-based, signature-based and network-based methods to predict repositioned drug candidates. The DrugRepoBank features an interactive and user-friendly web interface and offers comprehensive functionalities such as bioinformatics analysis of disease signatures. When users provide information about a drug, target or disease of interest, DrugRepoBank offers new indications and targets for the drug, proposes new drugs that bind to the target or suggests potential drugs for the queried disease. Additionally, it provides basic information about drugs, targets or diseases, along with supporting literature. We utilize three case studies to demonstrate the feasibility and effectiveness of predictively repositioned drugs within DrugRepoBank. The establishment of the DrugRepoBank database will significantly accelerate the pace of drug repositioning.

Database URL: https://awi.cuhk.edu.cn/DrugRepoBank
Long-term outcome after the Ross procedure in 173 adults with up to 25 years of follow-up
Authors: Van Hoof Lucas , Rooyackers Bert , Schuermans Art , Duponselle Jolien , Van De Bruaene Alexander , De Meester Pieter , Troost Els , Meuris Bart , Budts Werner , Gewillig Marc , Flameng Willem , Daenen Willem , Meyns Bart , Verbrugghe Peter , Rega Filip
Published: July 2024

OBJECTIVES

The potential risk of autograft dilatation and homograft stenosis after the Ross procedure mandates lifelong follow-up. This retrospective cohort study aimed to determine long-term outcome of the Ross procedure, investigating autograft and homograft failure patterns leading to reintervention.

METHODS

All adults who underwent the Ross procedure between 1991 and 2018 at the University Hospitals Leuven were included, with follow-up data collected retrospectively. Autograft implantation was performed using the full root replacement technique. The primary end-point was long-term survival. Secondary end-points were survival free from any reintervention, autograft or homograft reintervention-free survival, and evolution of autograft diameter, homograft gradient and aortic regurgitation grade over time.

RESULTS

A total of 173 adult patients (66% male) with a median age of 32 years (range 18–58 years) were included. External support at both the annulus and sinotubular junction was used in 38.7% (67/173). Median follow-up duration was 11.1 years (IQR, 6.4–15.9; 2065 patient-years) with 95% follow-up completeness. There was one (0.6%) perioperative death. Kaplan–Meier estimate for 15-year survival was 91.1% and Ross-related reintervention-free survival was 75.7% (autograft: 83.5%, homograft: 85%). Regression analyses demonstrated progressive neoaortic root dilatation (0.56 mm/year) and increase in homograft gradient (0.72 mmHg/year).

CONCLUSIONS

The Ross procedure has the potential to offer excellent long-term survival and reintervention-free survival. These long-term data further confirm that the Ross procedure is a suitable option in young adults with aortic valve disease which should be considered on an individual basis.
Safety of treating acute pulmonary embolism at home: an individual patient data meta-analysis
Authors: Luijten Dieuwke , Douillet Delphine , Luijken Kim , Tromeur Cecile , Penaloza Andrea , Hugli Olivier , Aujesky Drahomir , Barco Stefano , Bledsoe Joseph R , Chang Kyle E , Couturaud Francis , den Exter Paul L , Font Carme , Huisman Menno V , Jimenez David , Kabrhel Christopher , Kline Jeffrey A , Konstantinides Stavros , van Mens Thijs , Otero Remedios , Peacock W Frank , Sanchez Olivier , Stubblefield William B , Valerio Luca , Vinson David R , Wells Philip , van Smeden Maarten , Roy Pierre-Marie , Klok Frederikus A
Published: July 2024

Background and Aims

Home treatment is considered safe in acute pulmonary embolism (PE) patients selected by a validated triage tool (e.g. simplified PE severity index score or Hestia rule), but there is uncertainty regarding the applicability in underrepresented subgroups. The aim was to evaluate the safety of home treatment by performing an individual patient-level data meta-analysis.

Methods

Ten prospective cohort studies or randomized controlled trials were identified in a systematic search, totalling 2694 PE patients treated at home (discharged within 24 h) and identified by a predefined triage tool. The 14- and 30-day incidences of all-cause mortality and adverse events (combined endpoint of recurrent venous thromboembolism, major bleeding, and/or all-cause mortality) were evaluated. The relative risk (RR) for 14- and 30-day mortalities and adverse events is calculated in subgroups using a random effects model.

Results

The 14- and 30-day mortalities were 0.11% [95% confidence interval (CI) 0.0–0.24, I2 = 0) and 0.30% (95% CI 0.09–0.51, I2 = 0). The 14- and 30-day incidences of adverse events were 0.56% (95% CI 0.28–0.84, I2 = 0) and 1.2% (95% CI 0.79–1.6, I2 = 0). Cancer was associated with increased 30-day mortality [RR 4.9; 95% prediction interval (PI) 2.7–9.1; I2 = 0]. Pre-existing cardiopulmonary disease, abnormal troponin, and abnormal (N-terminal pro–)B-type natriuretic peptide [(NT-pro)BNP] at presentation were associated with an increased incidence of 14-day adverse events [RR 3.5 (95% PI 1.5–7.9, I2 = 0), 2.5 (95% PI 1.3–4.9, I2 = 0), and 3.9 (95% PI 1.6–9.8, I2 = 0), respectively], but not mortality. At 30 days, cancer, abnormal troponin, and abnormal (NT-pro)BNP were associated with an increased incidence of adverse events [RR 2.7 (95% PI 1.4–5.2, I2 = 0), 2.9 (95% PI 1.5–5.7, I2 = 0), and 3.3 (95% PI 1.6–7.1, I2 = 0), respectively].

Conclusions

The incidence of adverse events in home-treated PE patients, selected by a validated triage tool, was very low. Patients with cancer had a three- to five-fold higher incidence of adverse events and death. Patients with increased troponin or (NT-pro)BNP had a three-fold higher risk of adverse events, driven by recurrent venous thromboembolism and bleeding.
Pulmonary vein isolation using pulsed field ablation vs. high-power short-duration radiofrequency ablation in paroxysmal atrial fibrillation: efficacy, safety, and long-term follow-up (PRIORI study)
Authors: Reinsch Nico , Füting Anna , Hartl Stefan , Höwel Dennis , Rausch Eva , Lin Yali , Kasparian Karampet , Neven Kars
Published: July 2024

Aims

Pulsed field ablation (PFA) is a novel, non-thermal, cardiac tissue-selective ablation modality. To date, radiofrequency (RF)-guided high-power short-duration (HPSD) ablation represents the gold standard besides cryo-ablation for pulmonary vein isolation (PVI). This single-centre, retrospective study investigated the efficacy of PFA-PVI vs. HPSD-RF PVI in terms of single-procedure arrhythmia-free outcome and safety in a real-world setting.

Methods and results

Consecutive, paroxysmal atrial fibrillation (AF) patients who underwent PVI using PFA or HPSD-RF were enrolled. In group PFA, PVI was performed using a pentaspline PFA catheter. The ablation procedure in group HPSD-RF was performed with RF energy (45 W, ablation index). A total of 410 patients (group PFA, 201; group HPSD-RF, 209) were included. There was no difference between both groups regarding age, gender, and CHA2DS2-VASc score. The procedure time was significantly shorter in group PFA [61 (44–103) vs. 125 (105–143) min; P < 0.001]; fluoroscopy time and dose area product were significantly higher in group PFA [16 (13–20) vs. 4 (2–5) min; P < 0.01 and 412 (270–739) vs. 129 (58–265) μGym2; P < 0.01]. The overall complication rates were 2.9% in group PFA and 6.2% in group HPSD (P = 0.158). There was one fatal stroke in the PFA group. The 1-year Kaplan–Meier estimated freedom from any atrial tachyarrhythmia was 85% with PFA and 79% with HPSD-RF (log-rank P = 0.160). In 56 repeat ablation procedures, the PV reconnection rate was 30% after PFA and 38% after HPSD-RF (P = 0.372).

Conclusion

Both PFA and HPSD-RF were highly efficient and effective in achieving PVI in paroxysmal AF patients. The arrhythmia-free survival is comparable. The PV reconnection rate was not different.
Guidelines to practice in hospitals at home: safe and effective continuous infusion pumps substantially increased penicillin use in erysipelas treatment
Authors: Metsä-Simola Niina , Saarenketo Jenni , Lehtonen Henri , Broman Niklas , Häggblom Tony , Björklöf Pia , Sariola Salla , Valta Maija P
Published: July 2024

Hospitals at home are increasingly offering outpatient parenteral antimicrobial therapy (OPAT) in an attempt to reduce costly inpatient care, but these settings favour broad-spectrum antibiotics that require less frequent dosing than penicillin. Benzyl penicillin could be delivered via continuous infusion pumps (eCIPs), but studies on their safety and efficacy in OPAT are scarce, and it remains unclear how much the availability of eCIPs increases penicillin use in real-life settings. We examined 462 electronic healthcare records of erysipelas patients treated between January 2018 and January 2022 in a large Finnish OPAT clinic. Average marginal effects from logistic models were estimated to assess how the introduction of eCIPs in December 2020 affected penicillin use and to compare clinical outcomes between patients with and without eCIPs. Introduction of eCIPs increased the predicted probability of penicillin treatment by 36.0 percentage points (95% confidence interval 25.5–46.5). During eCIP implementation, patients who received an eCIP had 73.1 (58.0–88.2) percentage points higher probability than patients without an eCIP to receive penicillin treatment. They also had about 20 percentage points higher probability to be cured at the time of discharge and 3 months after it. Patient and nurse satisfaction regarding eCIPs was very high. Benzyl penicillin eCIP treatment is effective and safe, and substantially increases the use of penicillin instead of broad-spectrum antibiotics. To reduce the risk of antimicrobial resistance, eCIPs could increasingly be promoted for use in OPAT clinics, and there should be adequate education and support in their implementation.
Longitudinal Changes in a Claims-Based Frailty Proxy Measure Compared to Concurrent Changes in the Fried Frailty Phenotype
Authors: Duchesneau Emilie D , Kim Dae Hyun , Stürmer Til , Reeder-Hayes Katherine , Edwards Jessie K , Faurot Keturah R , Lund Jennifer L
Published: July 2024

Background

Frailty is a dynamic aging-related syndrome, but measuring frailty transitions is challenging. The Faurot frailty index is a validated Medicare claims-based frailty proxy based on demographic and billing information. We evaluated whether 3-year changes in the Faurot frailty index were consistent with concurrent changes in the frailty phenotype in a cohort of older adults.

Methods

We used longitudinal data from the National Health and Aging Trends Study (NHATS) with Medicare claims linkage (2010–2018). We identified older adults (66+ years) in the 2011 and 2015 NHATS cohorts with at least 1 year of Medicare fee-for-service continuous enrollment (N = 6 951). We described annual changes in mean claims-based frailty for up to 3 years, based on concurrent transitions in the frailty phenotype.

Results

At baseline, 32% were robust, 48% prefrail, and 19% frail based on the frailty phenotype. Mean claims-based frailty for older adults who were robust at baseline and worsened to frail increased over 3 years (0.09–0.25). Similarly, those who worsened from prefrail to frail experienced an increase in mean claims-based frailty (0.14–0.26). Improvements in the frailty phenotype did not correspond to decreases in claims-based frailty. Older adults whose frailty phenotype improved over time had a lower baseline claims-based frailty score than those who experienced stable or worsening frailty.

Conclusions

Older adults who experienced a frailty phenotype worsening over 3 years experienced concurrent increases in the Faurot frailty index. Our results suggest that claims data may be used to identify clinically meaningful worsening in frailty.
Long-term Trajectories of Low Back Pain in Older Men: A Prospective Cohort Study With 10-Year Analysis of the Osteoporotic Fractures in Men Study
Authors: McNaughton David T , Roseen Eric J , Patel Sheena , Downie Aron , Øverås Cecilie K , Nim Casper , Harsted Steen , Jenkins Hazel , Young James J , Hartvigsen Jan , Wong Jessica J , Stone Katie L , Ensrud Kristine E , Lee Soomi , Cawthon Peggy M , Fink Howard A
Published: July 2024

Although low back pain (LBP) may persist or recur over time, few studies have evaluated the individual course of LBP over a long-term period, particularly among older adults. Based on data from the longitudinal Osteoporotic Fractures in Men (MrOS) Study, we aimed to identify and describe different LBP trajectories in older men and characterize members in each trajectory group. A total of 5 976 community-dwelling men (mean age = 74.2) enrolled at 6 U.S. sites were analyzed. Participants self-reported LBP (yes/no) every 4 months for a maximum of 10 years. Latent class growth modeling was performed to identify unique LBP trajectory groups that explained variation in the LBP data. The association of baseline characteristics with trajectory group membership was assessed using univariable and multivariable multinominal logistic regression. A 5-class solution was chosen; no/rare LBP (n = 2 442/40.9%), low frequency-stable LBP (n = 1 040/17.4%), low frequency-increasing LBP (n = 719/12%), moderate frequency-decreasing LBP (n = 745/12.5%), and high frequency-stable LBP (n = 1 030/17.2%). History of falls (OR = 1.52), history of LBP (OR = 6.37), higher physical impairment (OR = 1.51–2.85), and worse psychological function (OR = 1.41–1.62) at baseline were all associated with worse LBP trajectory groups in this sample of older men. These findings present an opportunity for targeted interventions and/or management to older men with worse or increasing LBP trajectories and associated modifiable risk factors to reduce the impact of LBP and improve quality of life.
Mechanical Property, Efficacy, and User Experience of an Innovative Wearable Device in Preventing Fall-Induced Injuries
Authors: Hu Kaixin , Guan Zhongyang , He Zhijie , Luo Siran , Fang Hongbin , Zhang Yan , Ding Li , Xu Ying , Jiang Liuya , Fu Conghui , Zhao Xiaoqing , Jia Jie , Wu Chenkai
Published: July 2024

Background and Objectives

With the global population aging at an unprecedented pace, the imminent surge in falls and fall-induced injuries necessitates urgent attention. Innovative assistive technologies are crucial in addressing this daunting challenge. This study aimed to evaluate the mechanical properties, efficacy, safety, and user experience of the Intelligent Bone Protection Vest (IBPV), a novel, reusable, non-airbag wearable device.

Research Design and Methods

The IBPV integrates a machine learning-based algorithm for real-time monitoring of wearer motion and a unique honeycomb-structured foldable cushion for fall impact attenuation. We evaluated the impact attenuation capabilities of the IBPV and conducted 2 human subject studies to assess its efficacy and safety. Additionally, semistructured interviews were conducted to qualitatively explore its usability, safety, and opportunities for enhancement.

Results

The compression tests confirmed the energy absorption capacity of the honeycomb-structured foldable cushion. In over 800 fall tests involving 14 young and middle-aged subjects using a touchdown fall test, as well as 7 older subjects using a novel fall simulation test, the IBPV demonstrated an overall protection rate exceeding 84%.

Discussion and Implications

These results underscored the potential of the IBPV in reducing fall-induced injuries by mitigating the impact force on the hip during falls. Future studies with more rigorous design are needed to confirm whether this active wearable device may serve as a dependable fall protection product.
Multivariate variational mode decomposition to extract the stripe noise in GRACE harmonic coefficients
Authors: Jian Guangyu , Zou Fang , Xu Chuang , Yan Zhengwen
Published: July 2024

In this work, a novel method has been developed to remove the north–south stripe noise in the Level-2 spherical harmonic coefficient products collected by the Gravity Recovery and Climate Experiment (GRACE) mission. The proposed method extracts the stripe noise from the equivalent water height (EWH) map via the Multivariate Variational Mode Decomposition algorithm. The idea behind our method is to extract the cofrequency mode in multiple-channel series in the longitude direction. The parameters of our method are empirically determined. The investigation in a closed-loop simulation proves the improvement of our methods compared with the Singular Spectrum Analysis Spatial (SSAS) filter. Subsequently, the spatial-domain and spectral-domain investigations are conducted by using real GRACE data. Our method only suppresses stripe noise at low latitudes (30°S–30°N) and imposes an order-dependent impact on spherical harmonic coefficients but with potential oversmoothing. Meanwhile, the well-documented water level proves that our method further reduces outliers in a time-series of localized mass variations compared with the SSAS filter. More importantly, users are allowed to reduce the filtering strength of our method to preserve small-scale strong signals while suppressing stripe noise. Moreover, noise levels over the ocean at low latitudes are evaluated as well. The noise level of our method using empirical parameters is 32.48 mm of EWH, with 31.54 and 53.52 mm for DDK6 and SSAS, respectively. Our work introduces a novel method to address the issue of north–south stripe noise in the spatial domain.
Enzymatic glycosylation of aloesone performed by plant UDP-dependent glycosyltransferases
Authors: Putkaradze Natalia , Dato Laura , Kırtel Onur , Hansen Jørgen , Welner Ditte Hededam
Published: July 2024

Aloesone is a bioactive natural product and biosynthetic precursor of rare glucosides found in rhubarb and some aloe plants including Aloe vera. This study aimed to investigate biocatalytic aloesone glycosylation and more than 400 uridine diphosphate-dependent glycosyltransferase (UGT) candidates, including multifunctional and promiscuous enzymes from a variety of plant species were assayed. As a result, 137 selective aloesone UGTs were discovered, including four from the natural producer rhubarb. Rhubarb UGT72B49 was further studied and its catalytic constants (kcat = 0.00092 ± 0.00003 s−1, KM = 30 ± 2.5 μM) as well as temperature and pH optima (50 °C and pH 7, respectively) were determined. We further aimed to find an efficient aloesone glycosylating enzyme with potential application for biocatalytic production of the glucoside. We discovered UGT71C1 from Arabidopsis thaliana as an efficient aloesone UGT showing a 167-fold higher catalytic efficiency compared to that of UGT72B49. Interestingly, sequence analysis of all the 137 newly identified aloesone UGTs showed that they belong to different phylogenetic groups, with the highest representation in groups B, D, E, F and L. Finally, our study indicates that aloesone C-glycosylation is highly specific and rare, since it was not possible to achieve in an efficient manner with any of the 422 UGTs assayed, including multifunctional GTs and 28 known C-UGTs.
Why Patents on Climate Technologies Must Be Cut Short
Authors: Van Dycke Lodewijk
Published: July 2024

This contribution questions the term of protection for patents under circumstances of climate change. Patents typically last for 20 years but, for climate-related technologies, this is arguably too long. Under the 1.5°C scenario of the Paris Agreement, we need to make significant headway before 2030. Luckily, the technologies that need to be implemented broadly to reach the 2030 threshold have been developed already. To save civilisation from the worst impacts of climate change, the roll-out of existing technologies (static efficiency) is more important than the development of new ones (dynamic efficiency).

However, patent terms take neither static efficiency nor the climate timeframe into account. Technologies developed today will come off patent only in the 2040s, limiting their free availability when their wide roll-out should be the main concern. Conversely, the climate technologies that come off patent today were developed in the early 2000s, long before climate change acquired its current urgency and investment in climate technologies was ramped up.

These developments show that innovation systems for climate change have worked well, but they also show how terms of protection may now curtail the usefulness of past innovations. The contribution will analyse patent terms from a domestic and an international political economy perspective. The contribution will argue that, on balance, the situation requires a change of the TRIPS Agreement to shorten the term of patents on mature climate technologies. The TRIPS-waiver for patents on COVID-19 vaccines provides a partial precedent.
Siderophore interactions drive the ability of Pseudomonas spp. consortia to protect tomato against
Ralstonia solanacearum
Authors: Shao Zhengying , Gu Shaohua , Zhang Xiaoni , Xue Jiao , Yan Tao , Guo Saisai , Pommier Thomas , Jousset Alexandre , Yang Tianjie , Xu Yangchun , Shen Qirong , Wei Zhong
Published: July 2024

The soil-borne bacterial pathogen Ralstonia solanacearum causes significant losses in Solanaceae crop production worldwide, including tomato, potato, and eggplant. To efficiently prevent outbreaks, it is essential to understand the complex interactions between pathogens and the microbiome. One promising mechanism for enhancing microbiome functionality is siderophore-mediated competition, which is shaped by the low iron availability in the rhizosphere. This study explores the critical role of iron competition in determining microbiome functionality and its potential for designing high-performance microbiome engineering strategies. We investigated the impact of siderophore-mediated interactions on the efficacy of Pseudomonas spp. consortia in suppressing R. solanacearum, both in vitro and in vivo. Our findings show that siderophore production significantly enhances the inhibitory effects of Pseudomonas strains on pathogen growth, while other metabolites are less effective under iron-limited conditions. Moreover, siderophores play a crucial role in shaping interactions within the consortia, ultimately determining the level of protection against bacterial wilt disease. This study highlights the key role of siderophores in mediating consortium interactions and their impact on tomato health. Our results also emphasize the limited efficacy of other secondary metabolites in iron-limited environments, underscoring the importance of siderophore-mediated competition in maintaining tomato health and suppressing disease.
Energetic Costs of Stress in Developing Fishes: Quantifying Allostasis and Allostatic Load
Authors: Hunt von Herbing Ione
Published: July 2024

Synopsis

Stress exerts negative effects on fish health through stimulation of the hypothalamic-pituitary-interrenal axis and autonomic nervous system, resulting in heightened neural and neuroendocrine responses. Energetic investment and physiological adaptation are then required to re-establish homeostatic stability or reach a new allostatic state. The cost of the energetic investment is referred to as allostatic load (AL). While determining the sources of stress and assessing their consequences have resulted in estimates of AL, most of this work has been conducted in adult mammals and humans; no ALs exist for developing fish. From a series of experiments on a model species, zebrafish (Danio rerio), whose yolk-sac larvae were exposed to two chronic stressors (high-temperature and hypoxia), ALs were quantified based on biomarkers of ontogenetic changes in growth, morphometrics, and metabolic activities. Results showed that for zebrafish yolk-sac larvae, chronic stress imposed high AL and, thus, high total allostatic energetic costs, (Rt (AL)), because of prolonged energy demand in the face of limited resources (e.g., yolk). Under severe chronic stress, energetic costs were sufficiently large that energy-limited developing fish may not be able to fully compensate, resulting in maladaptive responses from allostatic overload, leading either to death or to novel allostatic states, possibly more resilient to environmental change.
The surgical outcome of standard lobectomy versus sleeve lobectomy in patients with non-small cell lung cancer: propensity score matching
Authors: Ülker Melike , Ağkoç Melek , Amirov Fahmin , Duman Salih , Özkan Berker , Erelel Mustafa , Kara Murat , Toker Alper
Published: July 2024

OBJECTIVES

The goal of this study was to compare the patients who underwent standard or sleeve lobectomy for non-small cell lung cancer in terms of postoperative outcomes, prognostic factors and overall survival.

METHODS

Between January 2002 and January 2020, the patients with squamous cell carcinoma or adenocarcinoma who underwent standard lobectomy or sleeve lobectomy by thoracotomy in our clinic were analysed retrospectively. Standard and sleeve groups were compared after propensity score matching in terms of age, comorbidity, T status, N status and pathological stage. Primary outcomes were morbidity and mortality; the secondary outcome was overall survival.

RESULTS

The study included 476 patients, and sleeve lobectomy was performed in 196 (41.1%) patients. Multivariable analysis revealed that age over 61 years (P = 0.003 and P = 0.005, respectively), forced expiratory volume in 1 s (FEV1) below 84% (P = 0.013 and P = 0.205, respectively) and the presence of perineural invasion (P = 0.052 and P = 0.001, respectively) were poor prognostic factors in the standard lobectomy and the sleeve groups. The propensity matching analysis included 276 patients (138 sleeve lobectomy and 138 standard lobectomy). Complications occurred in 96 (69.6%) and 92 (66.7%) patients in the standard and sleeve groups, respectively (P = 0.605). Three (2.2%) patients in the standard group and 5 (3.6%) patients in the sleeve group died within 90 days postoperatively (P = 0.723).

CONCLUSIONS

Bronchial sleeve lobectomy is a safe procedure that can be applied in oncologically suitable cases without causing higher mortality than a standard lobectomy.
Inverse probability weighting for self-selection bias correction in the investigation of social inequality in mortality
Authors: Petersen Gitte Lindved , Jørgensen Terese Sara Høj , Mathisen Jimmi , Osler Merete , Mortensen Erik Lykke , Molbo Drude , Hougaard Charlotte Ørsted , Lange Theis , Lund Rikke
Published: July 2024

Background

Empirical evaluation of inverse probability weighting (IPW) for self-selection bias correction is inaccessible without the full source population. We aimed to: (i) investigate how self-selection biases frequency and association measures and (ii) assess self-selection bias correction using IPW in a cohort with register linkage.

Methods

The source population included 17 936 individuals invited to the Copenhagen Aging and Midlife Biobank during 2009–11 (ages 49–63 years). Participants counted 7185 (40.1%). Register data were obtained for every invited person from 7 years before invitation to the end of 2020. The association between education and mortality was estimated using Cox regression models among participants, IPW participants and the source population.

Results

Participants had higher socioeconomic position and fewer hospital contacts before baseline than the source population. Frequency measures of participants approached those of the source population after IPW. Compared with primary/lower secondary education, upper secondary, short tertiary, bachelor and master/doctoral were associated with reduced risk of death among participants (adjusted hazard ratio [95% CI]: 0.60 [0.46; 0.77], 0.68 [0.42; 1.11], 0.37 [0.25; 0.54], 0.28 [0.18; 0.46], respectively). IPW changed the estimates marginally (0.59 [0.45; 0.77], 0.57 [0.34; 0.93], 0.34 [0.23; 0.50], 0.24 [0.15; 0.39]) but not only towards those of the source population (0.57 [0.51; 0.64], 0.43 [0.32; 0.60], 0.38 [0.32; 0.47], 0.22 [0.16; 0.29]).

Conclusions

Frequency measures of study participants may not reflect the source population in the presence of self-selection, but the impact on association measures can be limited. IPW may be useful for (self-)selection bias correction, but the returned results can still reflect residual or other biases and random errors.
Constitutionalizing Protection for Refugee Women and Girls in South Asia
Authors: Shanker Roshni
Published: July 2024

The South Asian region remains an epicentre of forced migration. Women comprise about half the region’s refugee population, and many are traumatized by sexual and gender-based violence (SGBV) experienced in their countries of origin and during flight. The 1951 Refugee Convention is not well ratified in the region and few States have developed domestic asylum laws, relying instead on ad hoc policies, core rule of law principles, and constitutional provisions to facilitate refugees’ access to essential legal protections. Many refugees in South Asia do not have a clear legal status, which can exacerbate rights violations, including SGBV. Over the years, through judicial activism, courts have developed a layered refugee law jurisprudence relying on criminal justice principles, executive orders, corresponding laws, and key international human rights treaties. These efforts have been complemented by the evolution of several formal and informal systems at the grassroots level, such as community-based dispute resolution mechanisms and State-run legal aid services, which have allowed refugee women and girls to access justice systems and seek redress. This article examines the legal strategies adopted by courts in Bangladesh, Pakistan, and India to uphold the rights of refugee women and girls and to protect survivors of SGBV, in particular.
Relative Contribution of Diagnostic Testing to the Diagnosis of Respiratory Syncytial Virus in Hospitalized Adults in the United States
Authors: Anderson Evan J , Tippett Ashley , Begier Elizabeth , Gibson Theda , Ess Gabby , Patel Vikash , Taylor Meg , Reese Olivia , Salazar Luis , Jadhao Samadhan , Sun He-Ying , Hsiao Hui-Mien , Gupta Shadwal , Li Wensheng , Stephens Kathleen , Keane Amy , Ciric Caroline , Hellmeister Kieffer , Cheng Andrew , Al-Husein Zayna , Bristow Laurel , Hubler Robin , Liu Qing , Gessner Bradford D , Jodar Luis , Swerdlow David , Kalina Warren , Uppal Sonal , Kamidani Satoshi , Rouphael Nadine , Anderson Larry J , Rostad Christina A
Published: July 2024

Background

Respiratory syncytial virus (RSV) is a leading cause of acute respiratory illness (ARI) in older adults. Optimizing diagnosis could improve understanding of RSV burden.

Methods

We enrolled adults ≥50 years of age hospitalized with ARI and adults of any age hospitalized with congestive heart failure or chronic obstructive pulmonary disease exacerbations at 2 hospitals during 2 respiratory seasons (2018–2020). We collected nasopharyngeal (NP) and oropharyngeal (OP) swabs (n = 1558), acute and convalescent sera (n = 568), and expectorated sputum (n = 153) from participants, and recorded standard-of-care (SOC) NP results (n = 805). We measured RSV antibodies by 2 immunoassays and performed BioFire testing on respiratory specimens.

Results

Of 1558 eligible participants, 92 (5.9%) tested positive for RSV by any diagnostic method. Combined NP/OP polymerase chain reaction (PCR) testing yielded 58 positives, while separate NP and OP testing identified 11 additional positives (18.9% increase). Compared to study NP/OP PCR alone, the addition of paired serology increased RSV detection by 42.9% (28 vs 40) among those with both specimen types, while the addition of SOC swab PCR increased RSV detection by 25.9% (47 vs 59).

Conclusions

The addition of paired serology testing, SOC swab results, and separate testing of NP and OP swabs improved RSV diagnostic yield in hospitalized adults.
Applications of Machine Learning on Electronic Health Record Data to Combat Antibiotic Resistance
Authors: Blechman Samuel E , Wright Erik S
Published: July 2024

There is growing excitement about the clinical use of artificial intelligence and machine learning (ML) technologies. Advancements in computing and the accessibility of ML frameworks enable researchers to easily train predictive models using electronic health record data. However, several practical factors must be considered when employing ML on electronic health record data. We provide a primer on ML and approaches commonly taken to address these challenges. To illustrate how these approaches have been applied to address antimicrobial resistance, we review the use of electronic health record data to construct ML models for predicting pathogen carriage or infection, optimizing empiric therapy, and aiding antimicrobial stewardship tasks. ML shows promise in promoting the appropriate use of antimicrobials, although clinical deployment is limited. We conclude by describing the potential dangers of, and barriers to, implementation of ML models in the clinic.