bluuebunny/crossref_metadata_2025 huggingface dataset:
High-sensitivity troponins and mortality in the general population
Authors: McEvoy John W , Daya Natalie , Tang Olive , Fang Michael , Ndumele Chiadi E , Coresh Josef , Christenson Robert H , Selvin Elizabeth
Published: June 2023

Aims

Cardiac troponin T and I can be measured using a number of high-sensitivity (hs) assays. This study aimed to characterize correlations between four such assays and test their comparative associations with mortality.

Methods and results

Among adults without cardiovascular disease in the 1999–2004 National Health and Nutrition Examination Survey, hs-troponin T was measured using one assay (Roche) and hs-troponin I using three assays (Abbott, Siemens, and Ortho). Cox regression was used to estimate associations with all-cause and cardiovascular mortality. Pearson’s correlation coefficients comparing concentrations from each assay ranged from 0.53 to 0.77. There were 2188 deaths (488 cardiovascular) among 9810 participants. Each hs-troponin assay [log-transformed, per 1 standard deviation (SD)] was independently associated with all-cause mortality: hazard ratio (HR) 1.20 [95% confidence interval (CI) 1.13–1.28] for Abbott hs-troponin I; HR 1.10 (95% CI 1.02–1.18) for Siemens hs-troponin I; HR 1.23 (95% CI 1.14–1.33) for Ortho hs-troponin I; and HR 1.31 (95% CI 1.21–1.42) for Roche hs-troponin T. Each hs-troponin assay was also independently associated with cardiovascular mortality (HR 1.44 to 1.65 per 1 SD). Associations of hs-troponin T and all-cause and cardiovascular mortality remained significant after adjusting for hs-troponin I. Furthermore, associations of hs-troponin I remained significant after mutually adjusting for hs-troponin I from the other individual assays: e.g. cardiovascular mortality HR 1.46 (95% CI 1.19–1.79) for Abbott after adjustment for the Siemens assay and HR 1.29 (95% CI 1.09–1.53) for Abbott after adjustment for the Ortho assay.

Conclusion

This study demonstrates only modest correlations between hs-troponin T and three hs-troponin I assays and that hs-troponin I assays can provide distinct risk information for mortality in the general population.
Improving 10-year cardiovascular risk prediction in apparently healthy people: flexible addition of risk modifiers on top of SCORE2
Authors: Hageman Steven H J , Petitjean Carmen , Pennells Lisa , Kaptoge Stephen , Pajouheshnia Romin , Tillmann Taavi , Blaha Michael J , McClelland Robyn L , Matsushita Kunihiro , Nambi Vijay , Klungel Olaf H , Souverein Patrick C , van der Schouw Yvonne T , Verschuren W M Monique , Lehmann Nils , Erbel Raimund , Jöckel Karl-Heinz , Di Angelantonio Emanuele , Visseren Frank L J , Dorresteijn Jannick A N
Published: June 2023

Aims

In clinical practice, factors associated with cardiovascular disease (CVD) like albuminuria, education level, or coronary artery calcium (CAC) are often known, but not incorporated in cardiovascular risk prediction models. The aims of the current study were to evaluate a methodology for the flexible addition of risk modifying characteristics on top of SCORE2 and to quantify the added value of several clinically relevant risk modifying characteristics.

Methods and results

Individuals without previous CVD or DM were included from the UK Biobank; Atherosclerosis Risk in Communities (ARIC); Multi-Ethnic Study of Atherosclerosis (MESA); European Prospective Investigation into Cancer, The Netherlands (EPIC-NL); and Heinz Nixdorf Recall (HNR) studies (n = 409 757) in whom 16 166 CVD events and 19 149 non-cardiovascular deaths were observed over exactly 10.0 years of follow-up. The effect of each possible risk modifying characteristic was derived using competing risk-adjusted Fine and Gray models. The risk modifying characteristics were applied to individual predictions with a flexible method using the population prevalence and the subdistribution hazard ratio (SHR) of the relevant predictor. Risk modifying characteristics that increased discrimination most were CAC percentile with 0.0198 [95% confidence interval (CI) 0.0115; 0.0281] and hs-Troponin-T with 0.0100 (95% CI 0.0063; 0.0137). External validation was performed in the Clinical Practice Research Datalink (CPRD) cohort (UK, n = 518 015, 12 675 CVD events). Adjustment of SCORE2-predicted risks with both single and multiple risk modifiers did not negatively affect calibration and led to a modest increase in discrimination [0.740 (95% CI 0.736–0.745) vs. unimproved SCORE2 risk C-index 0.737 (95% CI 0.732–0.741)].

Conclusion

The current paper presents a method on how to integrate possible risk modifying characteristics that are not included in existing CVD risk models for the prediction of CVD event risk in apparently healthy people. This flexible methodology improves the accuracy of predicted risks and increases applicability of prediction models for individuals with additional risk known modifiers.
Community factors and excess mortality in the COVID-19 pandemic in England, Italy and Sweden
Authors: Parkes Brandon , Stafoggia Massimo , Fecht Daniela , Davies Bethan , Bonander Carl , de’ Donato Francesca , Michelozzi Paola , Piel Frédéric B , Strömberg Ulf , Blangiardo Marta
Published: June 2023

Background

Analyses of coronavirus disease 19 suggest specific risk factors make communities more or less vulnerable to pandemic-related deaths within countries. What is unclear is whether the characteristics affecting vulnerability of small communities within countries produce similar patterns of excess mortality across countries with different demographics and public health responses to the pandemic. Our aim is to quantify community-level variations in excess mortality within England, Italy and Sweden and identify how such spatial variability was driven by community-level characteristics.

Methods

We applied a two-stage Bayesian model to quantify inequalities in excess mortality in people aged 40 years and older at the community level in England, Italy and Sweden during the first year of the pandemic (March 2020–February 2021). We used community characteristics measuring deprivation, air pollution, living conditions, population density and movement of people as covariates to quantify their associations with excess mortality.

Results

We found just under half of communities in England (48.1%) and Italy (45.8%) had an excess mortality of over 300 per 100 000 males over the age of 40, while for Sweden that covered 23.1% of communities. We showed that deprivation is a strong predictor of excess mortality across the three countries, and communities with high levels of overcrowding were associated with higher excess mortality in England and Sweden.

Conclusion

These results highlight some international similarities in factors affecting mortality that will help policy makers target public health measures to increase resilience to the mortality impacts of this and future pandemics.
Age and sex differences in cause-specific excess mortality and years of life lost associated with COVID-19 infection in the Swedish population
Authors: Lundberg Christina E , Santosa Ailiana , Björk Jonas , Brandén Maria , Cronie Ottmar , Lindgren Martin , Edqvist Jon , Åberg Maria , Adiels Martin , Rosengren Annika
Published: June 2023

Background

Estimating excess mortality and years of life lost (YLL) attributed to coronavirus disease 19 (COVID-19) infection provides a comprehensive picture of the mortality burden on society. We aimed to estimate the impact of the COVID-19 pandemic on age- and sex-specific excess mortality and YLL in Sweden during the first 17 months of the pandemic.

Methods

In this population-based observational study, we calculated age- and sex-specific excess all-cause mortality and excess YLL during 2020 and the first 5 months of 2021 and cause-specific death [deaths from cardiovascular disease (CVD), cancer, other causes and deaths excluding COVID-19] in 2020 compared with an average baseline for 2017–19 in the whole Swedish population.

Results

COVID-19 deaths contributed 9.9% of total deaths (98 441 deaths, 960 305 YLL) in 2020, accounting for 75 151 YLL (7.7 YLL/death). There were 2672 (5.7%) and 1408 (3.0%) excess deaths, and 19 141 (3.8%) and 3596 (0.8%) excess YLL in men and women, respectively. Men aged 65–110 years and women aged 75–110 years were the greatest contributors. Fewer deaths and YLL from CVD, cancer and other causes were observed in 2020 compared with the baseline adjusted to the population size in 2020.

Conclusions

Compared with the baseline, excess mortality and YLL from all causes were experienced in Sweden during 2020, with a higher excess observed in men than in women, indicating that more men died at a younger age while more women died at older ages than expected. A notable reduction in deaths and YLL due to CVD suggests a displacement effect from CVD to COVID-19.
Automatic Differentiation is no Panacea for Phylogenetic Gradient Computation
Authors: Fourment Mathieu , Swanepoel Christiaan J , Galloway Jared G , Ji Xiang , Gangavarapu Karthik , Suchard Marc A , Matsen IV Frederick A
Published: June 2023

Gradients of probabilistic model likelihoods with respect to their parameters are essential for modern computational statistics and machine learning. These calculations are readily available for arbitrary models via “automatic differentiation” implemented in general-purpose machine-learning libraries such as TensorFlow and PyTorch. Although these libraries are highly optimized, it is not clear if their general-purpose nature will limit their algorithmic complexity or implementation speed for the phylogenetic case compared to phylogenetics-specific code. In this paper, we compare six gradient implementations of the phylogenetic likelihood functions, in isolation and also as part of a variational inference procedure. We find that although automatic differentiation can scale approximately linearly in tree size, it is much slower than the carefully implemented gradient calculation for tree likelihood and ratio transformation operations. We conclude that a mixed approach combining phylogenetic libraries with machine learning libraries will provide the optimal combination of speed and model flexibility moving forward.
Trans reproduction: Continuity, cis-normativity, and trans inequality in law
Authors: Sørlie Anniken
Published: June 2023

In recent years, increasing numbers of jurisdictions are abolishing sterilization requirements for legal gender recognition and are introducing self-declared change of legal gender. The abolition of this requirement leads to a change in the reproductive capacities of legal men and legal women, enabling legal men to become pregnant and to give birth, and legal women to beget children. The change in the reproductive capacities of the legal genders leads to biopolitical questions about how states do and should govern trans reproduction after decades of state-regulated sterilization. This article uses the situation in Norway to explore the regulation of trans reproduction and aims to explain why trans people’s reproductive rights are lesser than those of cis people. It first investigates the Norwegian regulation of medically assisted reproduction and how it applies to people who have changed their legal gender. It shows that trans people are excluded from accessing medically assisted reproduction because their legal gender does not fit the conceptions of reproduction and gender under the Norwegian Biotechnology Act. Second, the article explores why trans people’s reproductive rights are limited, and argues that the law is based on cis-normative assumptions about reproduction, pregnancy, and the desire to become pregnant. Such assumptions, it is argued, permeate the law and lead to discrimination against trans people. The Norwegian legislature has not given any reasons as to why trans people’s reproductive rights are limited. The article demonstrates that although the sterilization requirement for legal gender recognition is abolished, the law continues to concentrate on cis realities and to restrict trans people’s ability to form a family with children.
Grounded in reality: artificial intelligence in medical education
Authors: Krive Jacob , Isola Miriam , Chang Linda , Patel Tushar , Anderson Max , Sreedhar Radhika
Published: June 2023

Background

In a recent survey, medical students expressed eagerness to acquire competencies in the use of artificial intelligence (AI) in medicine. It is time that undergraduate medical education takes the lead in helping students develop these competencies. We propose a solution that integrates competency-driven AI instruction in medical school curriculum.

Methods

We applied constructivist and backwards design principles to design online learning assignments simulating the real-world work done in the healthcare industry. Our innovative approach assumed no technical background for students, yet addressed the need for training clinicians to be ready to practice in the new digital patient care environment. This modular 4-week AI course was implemented in 2019, integrating AI with evidence-based medicine, pathology, pharmacology, tele-monitoring, quality improvement, value-based care, and patient safety.

Results

This educational innovation was tested in 2 cohorts of fourth year medical students who demonstrated an improvement in knowledge with an average quiz score of 97% and in skills with an average application assignment score of 89%. Weekly reflections revealed how students learned to transition from theory to practice of AI and how these concepts might apply to their upcoming residency training programs and future medical practice.

Conclusions

We present an innovative product that achieves the objective of competency-based education of students regarding the role of AI in medicine. This course can be integrated in the preclinical years with a focus on foundational knowledge, vocabulary, and concepts, and in clinical years with a focus on application of core knowledge to real-world scenarios.
Biological traits of the zoophytophagous predatory mirid Nesidiocoris poppiusi (Heteroptera: Miridae), a candidate biocontrol agent in China
Authors: Wang Lili , Zhang Yibo , Huang Ningxing , Di Ning , Tian Lixia , Zhu Zhengyang , Liu Junxiu , Wang Su
Published: June 2023

Mirid predators are increasingly used in biological control of multiple greenhouse crops pests. However, due to great morphological similarity and tiny body size, some mirid predators have been largely confused with their allied species. Nesidiocoris tenuis Reuter as a commercial mirid predator was confused largely with Nesidiocoris poppiusi Carvalho in China. To evaluate the biocontrol potential of N. poppiusi, its biological traits and the functional response to Bemisia tabaci Gennadius were studied compared with N. tenuis under laboratory conditions. The results showed that no significant differences of the developmental times from the first instar to adult stages between the 2 mirids fed on Corcyra cephalonica Stainton eggs were observed, while N. poppiusi had better population growth parameters than N. tenuis. Under the condition with prey, both female and male of N. poppiusi lived significantly longer than those of N. tenuis. It could lay 74.0 eggs, which was significantly higher than that of N. tenuis (30.2 eggs). Under the condition without prey, both N. poppiusi and N. tenuis couldn't complete development to adulthood on tomato, tobacco, muskmelon, and cabbage leaves, however, tobacco and tomato were more suitable than the other 2 plants. A type II functional response was observed for both males and females of the 2 predators. Nesidiocoris poppiusi females consumed significantly more B. tabaci pupae than N. tenuis when prey densities were large than 30. Our results indicated that N. poppiusi could be a promising candidate for biological control of B. tabaci.
Lazarus stars: numerical investigations of stellar evolution with star-lifting as a life extension strategy
Authors: Scoggins Matthew T , Kipping David
Published: June 2023

The aging and gradual brightening of the Sun will challenge Earth’s habitability in the next few billion years. If life exists elsewhere in the Universe, the aging of its host star similarly poses an existential threat. One solution, which we dub a Lazarus star, is for an advanced civilization to remove (or star-lift) mass from their host star at a rate that offsets the increase in luminosity, keeping the flux on the habitable planet(s) constant and extending the lifetime of their star. While this idea has existed since 1985 when it was first proposed by Criswell, numerical investigations of star-lifting have been lacking. Here, we use the stellar evolution code mesa to find mass versus age and $\dot{M}$ versus age relations that would hold the flux on surrounding planets constant. We explore initial mass ranging from $0.2$ to $1.2\, {\rm M}_{\odot }$. For most stars with a mass initially below about 0.4 M⊙, we find that star-lifting increases their main-sequence lifetimes up to 500 Gyr until they approach the hydrogen burning limit and star-lifting is no longer possible. For more massive stars, star-lifting increases main-sequence lifetimes by 1–100 Gyr, though they still enter the red-giant phase. For example, a Sun-like star has a main-sequence lifetime that can be increased by up to 3 Gyr. This requires a mass-loss rate of about $0.05\, {\rm \mathit{ M}}_{\mathrm{Ceres}}$ per year. We compare star-lifting to other survival strategies and briefly discuss methods for detecting these engineered stars.
A different view of wind in X-ray binaries: the accretion disc corona source 2S 0921-630
Authors: Tomaru Ryota , Done Chris , Odaka Hirokazu , Tanimoto Atsushi
Published: June 2023

Accretion disc coronae (ADC) sources are very high inclination neutron star or black hole binaries, where the outer accretion flow blocks a direct view of the central source. The weak observed X-ray emission is instead produced mainly by scattering of the intrinsic radiation from highly ionized gas surrounding the source, the ADC. However, the origin of this scattering material is still under debate. We use the ADC source 2S 0921-630 (V395 Car) to test whether it is consistent with a thermal-radiative wind produced by the central X-ray source illuminating and puffing up the outer disc. This wind is clearly visible in blueshifted absorption lines in less highly inclined systems, where the source is seen directly through this material. Using the phenomenological photoionized plasma model, we first characterize the parameter that drives emission lines observed in 2S0921 in XMM–Newton and Chandra data. Following this, we run the Monte Carlo radiation transfer simulation to get scattered/reprocessed emissions in the wind, with the density and velocity structure obtained from the previous work. Our model agrees with all the wind emission lines in the Chandra high and medium energy grating spectra for an intrinsic source luminosity of L > 0.2 LEdd. This result strongly favours thermal-radiative winds as the origin of the ADC. We also show how high-resolution spectra via microcalorimeters can provide a definitive test by detecting blueshifted absorption lines.
Multiomic analysis of cohesin reveals that ZBTB transcription factors contribute to chromatin interactions
Authors: Wang Rui , Xu Qiqin , Wang Chenlu , Tian Kai , Wang Hui , Ji Xiong
Published: June 2023

One bottleneck in understanding the principles of 3D chromatin structures is caused by the paucity of known regulators. Cohesin is essential for 3D chromatin organization, and its interacting partners are candidate regulators. Here, we performed proteomic profiling of the cohesin in chromatin and identified transcription factors, RNA-binding proteins and chromatin regulators associated with cohesin. Acute protein degradation followed by time-series genomic binding quantitation and BAT Hi-C analysis were conducted, and the results showed that the transcription factor ZBTB21 contributes to cohesin chromatin binding, 3D chromatin interactions and transcriptional repression. Strikingly, multiomic analyses revealed that the other four ZBTB factors interacted with cohesin, and double degradation of ZBTB21 and ZBTB7B led to a further decrease in cohesin chromatin occupancy. We propose that multiple ZBTB transcription factors orchestrate the chromatin binding of cohesin to regulate chromatin interactions, and we provide a catalog of many additional proteins associated with cohesin that warrant further investigation.
Mechanistic insight into AP-endonuclease 1 cleavage of abasic sites at stalled replication fork mimics
Authors: Hoitsma Nicole M , Norris Jessica , Khoang Thu H , Kaushik Vikas , Chadda Rahul , Antony Edwin , Hedglin Mark , Freudenthal Bret D
Published: June 2023

Many types of damage, including abasic sites, block replicative DNA polymerases causing replication fork uncoupling and generating ssDNA. AP-Endonuclease 1 (APE1) has been shown to cleave abasic sites in ssDNA. Importantly, APE1 cleavage of ssDNA at a replication fork has significant biological implications by generating double strand breaks that could collapse the replication fork. Despite this, the molecular basis and efficiency of APE1 processing abasic sites at replication forks remain elusive. Here, we investigate APE1 cleavage of abasic substrates that mimic APE1 interactions at stalled replication forks or gaps. We determine that APE1 has robust activity on these substrates, like dsDNA, and report rates for cleavage and product release. X-ray structures visualize the APE1 active site, highlighting an analogous mechanism is used to process ssDNA substrates as canonical APE1 activity on dsDNA. However, mutational analysis reveals R177 to be uniquely critical for the APE1 ssDNA cleavage mechanism. Additionally, we investigate the interplay between APE1 and Replication Protein A (RPA), the major ssDNA-binding protein at replication forks, revealing that APE1 can cleave an abasic site while RPA is still bound to the DNA. Together, this work provides molecular level insights into abasic ssDNA processing by APE1, including the presence of RPA.
Using Typhoid Conjugate Vaccines to Prevent Disease, Promote Health Equity, and Counter Drug-Resistant Typhoid Fever
Authors: Nampota-Nkomba Nginache , Carey Megan E , Jamka Leslie P , Fecteau Natalie , Neuzil Kathleen M
Published: June 2023

Typhoid fever is a serious disease that disproportionately impacts children in low-resource settings in sub-Saharan Africa, South and Southeast Asia, and the Western Pacific. The prevalence of antimicrobial-resistant strains of S. Typhi continue to increase worldwide. Two safe, effective, and cost-effective typhoid conjugate vaccines (TCVs) are World Health Organization-prequalified for the prevention of typhoid fever in children as young as 6 months. Typhoid conjugate vaccines have proven effectiveness in preventing drug-resistant S. Typhi and have been deployed successfully in outbreak response and routine immunization scenarios. Broad and equitable distribution of TCVs is essential to combat the spread and potentially devastating consequences of typhoid fever. It is vital to empower decision-makers in typhoid-endemic countries to introduce TCVs and for leaders to embrace this critical tool to prevent typhoid fever, slow the spread of drug-resistant S. Typhi strains, promote health equity, and save lives.
Informed consent practices in clinical research: present and future
Authors: Jawa Natasha A , Boyd J Gordon , Maslove David M , Scott Stephen H , Silver Samuel A
Published: June 2023

Clinical research must balance the need for ambitious recruitment with protecting participants’ autonomy; a requirement of which is informed consent. Despite efforts to improve the informed consent process, participants are seldom provided sufficient information regarding research, hindering their ability to make informed decisions. These issues are particularly pervasive among patients experiencing acute illness or neurological impairment, both of which may impede their capacity to provide consent. There is a critical need to understand the components, requirements, and methods of obtaining true informed consent to achieve the vast numbers required for meaningful research. This paper provides a comprehensive review of the tenets underlying informed consent in research, including the assessment of capacity to consent, considerations for patients unable to consent, when to seek consent from substitute decision-makers, and consent under special circumstances. Various methods for obtaining informed consent are addressed, along with strategies for balancing recruitment and consent.
Association between prolonged weekly duty hours and self-study time among residents: a cross-sectional study
Authors: Nagasaki Kazuya , Nishizaki Yuji , Shinozaki Tomohiro , Shimizu Taro , Yamamoto Yu , Shikino Kiyoshi , Fukui Sho , Nishiguchi Sho , Kurihara Masaru , Katayama Kohta , Kobayashi Hiroyuki , Tokuda Yasuharu
Published: June 2023

Purpose

In 2024, the Japanese government will enforce a maximum 80-hour weekly duty hours (DHs) regulation for medical residents. Although this reduction in weekly DHs could increase the self-study time (SST) of these residents, the relationship between these two variables remains unclear. The aim of the study was to investigate the relationship between the SST and DHs of residents in Japan.

Methods

In this nationwide cross-sectional study, the subjects were candidates of the General Medicine In-Training Examination in the 2020 academic year. We administered questionnaires and categorically asked questions regarding daily SST and weekly DHs during the training period. To account for hospital variability, proportional odds regression models with generalized estimating equations were used to analyse the association between SST and DHs.

Results

Of the surveyed 6117 residents, 32.0% were female, 49.1% were postgraduate year-1 residents, 83.8% were affiliated with community hospitals, and 19.9% worked for ≥80 hours/week. Multivariable analysis revealed that residents working ≥80 hours/week spent more time on self-study than those working 60–70 hours/week. Conversely, residents who worked <50 hours/week spent less time on self-study than those who worked 60–70 hours/week. The factors associated with longer SST were sex, postgraduate year, career aspiration for internal medicine, affiliation with community hospitals, academic involvement, and well-being.

Conclusion

Residents with long DHs had longer SSTs than residents with short DHs. Future DH restrictions may not increase but rather decrease resident SST. Effective measures to encourage self-study are required, as DH restrictions may shorten SST.
Effects of a Dedicated Cardiac Rehabilitation Program for Patients With Obesity on Body Weight, Physical Activity, Sedentary Behavior, and Physical Fitness: The OPTICARE XL Randomized Controlled Trial
Authors: den Uijl Iris , van den Berg-Emons Rita J G , Sunamura Madoka , Lenzen Mattie J , Stam Henk J , Boersma Eric , Tenbült-van Limpt Nicole C C W , Kemps Hareld M C , Geleijnse Marcel L , ter Hoeve Nienke
Published: June 2023

Objective

Previously published results of the OPTICARE XL open label randomized controlled trial showed no added value of OPTICARE XL CR, a dedicated cardiac rehabilitation (CR) program for patients with obesity, with respect to health–related quality of life (primary outcome). This clinical trial studied the effects of OPTICARE XL CR on several secondary outcomes, which included body weight, physical activity, sedentary behavior, and physical fitness.

Methods

Patients with coronary artery disease or atrial fibrillation and body mass index ≥ 30 were randomized to OPTICARE XL CR (n = 102) or standard CR (n = 99). OPTICARE XL CR was a 1-year group intervention, specifically designed for patients with obesity that included aerobic and strength exercise, behavioral coaching, and an aftercare program. Standard CR consisted of a 6- to 12-week group aerobic exercise program, supplemented with cardiovascular lifestyle education. Study end points included body weight, physical activity, sedentary behavior (accelerometer), and physical fitness (6-Minute Walk Test and handgrip strength), which were evaluated 6 months after the end of CR (primary endpoint) and 3 months after the start of CR.

Results

Six months after completion of either program, improvements in body weight, physical activity, sedentary behavior, and physical fitness were similar between the groups. Three months after CR start, patients randomized to OPTICARE XL CR showed greater weight loss (mean change = −3.6 vs −1.8 kg) and a larger improvement in physical activity (+880 vs +481 steps per day) than patients randomized to standard CR.

Conclusion

Patients allocated to OPTICARE XL CR lost significantly more body weight and showed promising results with respect to physical activity 3 months after the start of CR; however, these short-term results were not expanded or sustained in the longer term.

Impact

Patients with obesity do not benefit from standard CR programs. The new OPTICARE XL CR program showed its effects in the short term on weight loss and physical activity, and, therefore, redesign of the aftercare phase is recommended.
Single-Cell RNA-Seq Reveals LRRC75A-Expressing Cell Population Involved in VEGF Secretion of Multipotent Mesenchymal Stromal/Stem Cells Under Ischemia
Authors: Miura Takumi , Kouno Tsukasa , Takano Megumi , Kuroda Takuya , Yamamoto Yumiko , Kusakawa Shinji , Morioka Masaki Suimye , Sugawara Tohru , Hirai Takamasa , Yasuda Satoshi , Sawada Rumi , Matsuyama Satoko , Kawaji Hideya , Kasukawa Takeya , Itoh Masayoshi , Matsuyama Akifumi , Shin Jay W , Umezawa Akihiro , Kawai Jun , Sato Yoji
Published: June 2023

Human multipotent mesenchymal stromal/stem cells (MSCs) have been utilized in cell therapy for various diseases and their clinical applications are expected to increase in the future. However, the variation in MSC-based product quality due to the MSC heterogeneity has resulted in significant constraints in the clinical utility of MSCs. Therefore, we hypothesized that it might be important to identify and ensure/enrich suitable cell subpopulations for therapies using MSC-based products. In this study, we aimed to identify functional cell subpopulations to predict the efficacy of angiogenic therapy using bone marrow-derived MSCs (BM-MSCs). To assess its angiogenic potency, we observed various levels of vascular endothelial growth factor (VEGF) secretion among 11 donor-derived BM-MSC lines under in vitro ischemic culture conditions. Next, by clarifying the heterogeneity of BM-MSCs using single-cell RNA-sequencing analysis, we identified a functional cell subpopulation that contributed to the overall VEGF production in BM-MSC lines under ischemic conditions. We also found that leucine-rich repeat-containing 75A (LRRC75A) was more highly expressed in this cell subpopulation than in the others. Importantly, knockdown of LRRC75A using small interfering RNA resulted in significant inhibition of VEGF secretion in ischemic BM-MSCs, indicating that LRRC75A regulates VEGF secretion under ischemic conditions. Therefore, LRRC75A may be a useful biomarker to identify cell subpopulations that contribute to the angiogenic effects of BM-MSCs. Our work provides evidence that a strategy based on single-cell transcriptome profiles is effective for identifying functional cell subpopulations in heterogeneous MSC-based products.
Extra-intestinal complications of Ascaris lumbricoides infections in India: A systematic review and meta-analysis
Authors: Mewara Abhishek , Kanaujia Rimjhim , Malla Nancy
Published: June 2023

The aberrant migration of Ascaris lumbricoides may cause extra-intestinal ascariasis (EIA) involving hepato-biliary-pancreatic (HBP) or other extra-gastro-intestinal (EGI) organs. We performed a systematic review and meta-analysis to study the risk factors and clinical presentations of EIA, and differences in HBP and EGI ascariasis. Medline, Web of Science and Embase were searched for cases of EIA in the English language from India. From 1204 articles, 86 studies (105 cases) were included. The majority of the cases involved the HBP system (78%). Among HBP ascariasis, the most commonly involved site was the bile duct (53.6%). Females had 11.3 times higher odds (95% CI 2.852 to 44.856; p=0.001) of HBP ascariasis, while the pediatric population had lower odds (OR=0.323). Previous gallbladder disease was significantly associated with HBP ascariasis in adults (p=0.046), while a significantly higher number of cases of EGI ascariasis were observed among pediatric patients (p=0.003). Ocular symptoms occurred exclusively in the pediatric population (p=0.017). Overall, death was reported in 3.8% of patients (n=4). This review emphasizes the importance of the complications of EIA. It encourages future research into issues such as the reasons of higher gall bladder ascariasis in females and the implications of Ascaris-related complications following biliary tract interventions. It also suggests considering Ascaris as a differential diagnosis for airway obstuction in intubated critically ill patients.
Murder and Memory in Territorial Hawai‘i: A Moloka‘i Microhistory
Authors: Hoxie Frederick E
Published: June 2023

The murder of Elmer Conant on the tiny island of Moloka‘i in June, 1923, was an act of local resistance to a wave of social and economic change. The hunt for Conant’s murderer, and the subsequent prosecution of a Native Hawaiian man local authorities believed was responsible for it, reveal the power territorial elites could exercise over life in rural Hawai‘i, the ambiguous nature of indigenous response to that rule, and the way colonial power could shape memories of the era. This microhistory reverses the conventional lens used to examine Hawaiian history by concentrating on rural events and ordinary people far removed from the capital city who confronted the forces of colonialism and whose struggles helped shape island history.
Continuous Finger-cuff versus Intermittent Oscillometric Arterial Pressure Monitoring and Hypotension during Induction of Anesthesia and Noncardiac Surgery: The DETECT Randomized Trial
Authors: Kouz Karim , Weidemann Friederike , Naebian Ashkan , Lohr Anneke , Bergholz Alina , Thomsen Kristen K. , Krause Linda , Petzoldt Martin , Moll-Khosrawi Parisa , Sessler Daniel I. , Flick Moritz , Saugel Bernd
Published: June 2023

Background

Finger-cuff methods allow noninvasive continuous arterial pressure monitoring. This study aimed to determine whether continuous finger-cuff arterial pressure monitoring helps clinicians reduce hypotension within 15 min after starting induction of anesthesia and during noncardiac surgery. Specifically, this study tested the hypotheses that continuous finger-cuff—compared to intermittent oscillometric—arterial pressure monitoring helps clinicians reduce the area under a mean arterial pressure of 65 mmHg within 15 min after starting induction of anesthesia and the time-weighted average mean arterial pressure less than 65 mmHg during noncardiac surgery.

Methods

In this single-center trial, 242 noncardiac surgery patients were randomized to unblinded continuous finger-cuff arterial pressure monitoring or to intermittent oscillometric arterial pressure monitoring (with blinded continuous finger-cuff arterial pressure monitoring). The first of two hierarchical primary endpoints was the area under a mean arterial pressure of 65 mmHg within 15 min after starting induction of anesthesia; the second primary endpoint was the time-weighted average mean arterial pressure less than 65 mmHg during surgery.

Results

Within 15 min after starting induction of anesthesia, the median (interquartile range) area under a mean arterial pressure of 65 mmHg was 7 (0, 24) mmHg × min in 109 patients assigned to continuous finger-cuff monitoring versus 19 (0.3, 60) mmHg × min in 113 patients assigned to intermittent oscillometric monitoring (P = 0.004; estimated location shift: −6 [95% CI: −15 to −0.3] mmHg × min). During surgery, the median (interquartile range) time-weighted average mean arterial pressure less than 65 mmHg was 0.04 (0, 0.27) mmHg in 112 patients assigned to continuous finger-cuff monitoring and 0.40 (0.03, 1.74) mmHg in 115 patients assigned to intermittent oscillometric monitoring (P < 0.001; estimated location shift: −0.17 [95% CI: −0.41 to −0.05] mmHg).

Conclusions

Continuous finger-cuff arterial pressure monitoring helps clinicians reduce hypotension within 15 min after starting induction of anesthesia and during noncardiac surgery compared to intermittent oscillometric arterial pressure monitoring.

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The Role of Remimazolam in Neurosurgery and in Patients With Neurological Diseases: A Narrative Review
Authors: Teixeira Miguel T. , Brinkman Nathan J. , Pasternak Jeffrey J. , Abcejo Arnoley S.
Published: June 2023

Remimazolam is a novel ultrashort-acting benzodiazepine that produces sedation by acting as a positive allosteric modulator of the gamma-amino butyric acid-A receptor. Its high water solubility and metabolism via tissue esterases allow for a rapid onset of sedation/anesthesia and prompt arousal despite prolonged use. In addition, the effects of remimazolam can be reversed with flumazenil. This narrative review discusses the role of remimazolam in patients undergoing neurosurgical and neuroradiological procedures, specifically its role during awake craniotomies and compatibility with neuromonitoring. Considerations for remimazolam use in patients with neurological diseases are also highlighted. In addition, the impact of remimazolam on postoperative excitation, risk for postoperative delirium, and delayed neurocognitive recovery are discussed. Although there seems to be a clinical promise for remimazolam based on limited case studies and our own institutional experience of its use, further clinical investigation is warranted to understand the potential impact of remimazolam on surgical and neurological outcomes.
The John Hopkins classification system used in pediatric supracondylar humerus fractures requires more experience than the Gartland system
Authors: Şahbat Yavuz , Bekiroğlu Gülnaz Nural , Çat Görkem , Gündoğdu Mert , Ağirdil Yücel , Onay Tolga , Akgülle Ahmet Hamdi
Published: June 2023

The Gartland classification is used to decide on surgery. In contrast, the John Hopkins classification system predicts clinical outcomes for patients undergoing surgery and determines the risk of reduction loss. This study aims to investigate the usability of the Gartland and the John Hopkins classification systems by pediatric and general orthopedic surgeons. The preoperative images of 200 patients who presented at a tertiary-level trauma center with a supracondylar humerus fracture were examined by 4 observers, twice at an interval of 6 weeks. The observers comprised 2 pediatric orthopedic surgeons and 2 orthopedics and traumatology surgeons. Inter- and intra-observer reliability were excellent for the first and second measurements of the Gartland classification. The inter-observer agreement of the pediatric orthopedic surgeons and the general orthopedic surgeons was found to be similar (ICC >90). Inter-observer reliability was excellent (ICC: 0.808) and good (ICC: 0.732) for the measurements of the John Hopkins classification, respectively. The inter-observer agreement of the pediatric orthopedic surgeons and the general orthopedic surgeons was not similar. The inter-observer agreement between the two pediatric orthopedic surgeons was excellent for the measurements (ICC: 0.868; ICC: 0.756, respectively). The inter-observer agreement between the two general orthopedic surgeons was good for the measurements (ICC: 0.605; ICC: 0.663, respectively). The John Hopkins classification system has good intra- and inter-observer reliability, and a high experience level increases the agreement. The Gartland classification system was not affected by experience. This should be considered when taking measurements in studies and patient management.
Intra- and inter-observer reliability of Dias-Tachdjian classification in pediatric ankle fractures: do clinical experience and expertise matter?
Authors: Demirel Mehmet , Yenigün Mehmet Yağiz , Mert Lezgin , Kendirci Alper Şükrü , Yağci Taha Furkan , Demir Taha Bedir , Sağlam Yavuz , Cirdi Yiğit , Yağdiran Burak , Korkmazer Bora
Published: June 2023

The Dias-Tachdjian classification is the most commonly used system for the classification of pediatric ankle fractures, but its inter- and intra-observer reliability has not been studied in detail. Also, the impact of the clinician’s experience and expertise on the reliability of this system is unknown. This study aimed: (1) to determine the intra- and inter-observer reliability of the Dias-Tachdjian classification and (2) to investigate the effect of the clinician’s experience and expertise on the reliability of this system. Anteroposterior and lateral ankle radiographs of 56 children (34 male, 22 female) with ankle fractures, aged between 3 and 14 years, with open growth cartilages, were retrospectively identified and included in the study. Each patient radiograph was examined by 10 observers from two different specialties with different levels of clinical experience (two orthopedic surgeons with interest in pediatric orthopedics, three orthopedic surgeons with no interest in pediatric orthopedics, three orthopedic residents, and two radiology specialists) from two different specialties (orthopedics and radiology). All observers were then asked to classify pediatric ankle fractures at 6-week intervals per the Dias-Tachdjian classification system. Overall, intra-observer reliability as substantial to very good (κ = 0.77–0.95, P < 0.01), but inter-observer reliability as fair for both assessments (κ = 0.21, P < 0.01 and κ = 0.20, P < 0.01 for the first and second occasions, respectively). Inter-observer reliability among pediatric orthopedic surgeons as very good (κ = 0.90, 95% CI = 0.86–0.94, P < 0.01 and κ = 0.82, 95% CI = 0.71–0.93, P < 0.01 for the first and second occasions, respectively). Orthopedic surgeons with no special interest in pediatric orthopedics demonstrated substantial agreement in the first occasion (κ = 0.63, 95% CI = 0.53–0.72, P < 0.01) but moderate in the second one. Orthopedic residents exhibited moderate levels of agreement in each assessment period (κ = 0.58, 95% CI = 0.47–0.68, P < 0.01 and κ = 0.44, 95% CI = 0.37–0.51, P < 0.01 for the first and second occasion, respectively). Considering that the specialists dealing with pediatric orthopedics show very good consistency for Dias-Tachdjian classification, both within and between observers, consistency in the identification of the ankle fracture models increases as the interest in the field of pediatric orthopedics intensifies.
ATV-Related Trauma in the Pediatric Population
Authors: Giertych Benjamin , Morrow Vincent R. , Rizwan Umer , Danby Grace C. , Lubicky John P. , Hobbs Gerald , Grant Daniel R.
Published: June 2023

Background:

All-terrain vehicles (ATVs) are prevalent in Appalachia and cause significant morbidity and mortality in the pediatric population. This study investigated the injury types and severity in pediatric patients over a 15-year period.

Methods:

A retrospective chart review was performed on pediatric ATV-related traumas presenting to our institution from 2005 to 2020. Patients were divided into 3 age groups (0–7, 8–12, and 13–17 y) to evaluate differences in accident demographics, hospitalization, Glasgow Coma Scale, Injury Severity Score, substance use, characterization of orthopaedic and nonorthopaedic injuries, and procedures performed.

Results:

Inclusion criteria were met by 802 patients. Males represented 71.7% (n=575) and females 28.3% (n=227); the mean age was 12.4 years. The majority (88.5%, n=710) of patients admitted following their accident had a mean stay length of 3.3 days. Of admissions, intensive care unit admission was required by 23.8%, n=191 (mean stay 4.0 d). There were 7 fatalities. The vast majority of accidents occurred between May and September (79.2%, n=635). In patients with documented helmet status, 45% (n=271) were helmeted. Roughly half of all patients (n=393) sustained a fracture (excluding fractures to the head), 370 sustained an injury to the head/face, 129 sustained intra-abdominal/intra-thoracic injuries, and 29 sustained injuries to all 3 systems. The most common fractures involved the forearm (n=98), femur (n=65), and spine (n=59). The most common open fractures were the tibia (n=12), humerus (n=8), and forearm (n=8). The oldest group was more likely than the middle or younger groups to sustain spine (P<0.0001), pelvis (P=0.0001), hand (P=0.0089), and foot (P=0.0487) fractures. Ethanol testing was positive in 5.0% (n=25) of the oldest group and cannabinoids were present in 6.8% (n=34). The youngest group was significantly more likely to sustain a fracture of the humerus than the middle or older groups (P<0.0001). Orthopaedic surgical management was required in 24.4% (n=196) of patients.

Conclusions:

Pediatric ATV accidents present a significant source of morbidity and mortality. Further intervention is necessary to minimize pediatric ATV injuries.

Level of Evidence:

Level IV—Retrospective Case Series.
Selpercatinib monotherapy in a Chinese patient with RET fusion/EGFR co-mutated nonsmall cell lung cancer from the Phase II LIBRETTO-321 study: a case report
Authors: Wu Lin , Cheng Ying , Huang Dingzhi , Sun Yuping , Zhou Chengzhi , Zhou Jianying , Guo Ye , Shao Jingxin , Zhang Wanli , Lu Shun
Published: June 2023

Rearranged during transfection (RET) fusions and epidermal growth factor receptor (EGFR) mutations are potent oncogenic drivers in patients with nonsmall cell lung cancer (NSCLC), but rarely co-exist. Concurrent RET/EGFR mutations have been reported in patients with NSCLC who develop resistance to EGFR tyrosine kinase inhibitors but are even less frequent in treatment-naïve patients. Consequently, there is no standard treatment for RET/EGFR-mutated NSCLC. We report a case of RET/EGFR mutant NSCLC successfully treated with the oral, potent, highly selective RET inhibitor selpercatinib (160 mg daily for 28-day cycles) in an ongoing phase II study in Chinese patients with NSCLC (LIBRETTO-321). The patient, a female nonsmoker, was diagnosed with de-novo left lung adenocarcinoma with neuroendocrine differentiation, and a RET fusion was detected by next-generation sequencing testing. The patient had two tumors in the pleura, a third in the subcarinal lymph node, and a nontarget tumor in the pleura. Pleural biopsy analysis confirmed a RET fusion KIF5B (K15;R12) and an EGFR exon 19 deletion. The patient achieved a partial response (PR) with selpercatinib (absence of target tumors in pleura and reduction in the size of lymph node tumor). The PR persisted for 14.7 months, with disease progression in the nontarget lesion in the pleura and a new lesion in the liver (the PR had persisted), resulting in the discontinuation of selpercatinib. The only notable adverse event was grade 3 elevated transaminase, that was effectively managed by dose reduction. These data may support the use of selpercatinib in patients with RET/EGFR co-mutated NSCLC.