bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of the Triglyceride‐Glucose Index With Resistant Hypertension and a Nomogram Model Construction
Authors: Yang Hai‐Tao , Liu Jing‐Kun , Liu Bang‐Quan , Yang Yi , Xie Xiang
Published: September 2024

Background

Resistant hypertension (RH) remains one of the major risk factors for cardiovascular disease. This study aims to investigate the association between the triglyceride‐glucose (TyG) index and RH incidence in patients with hypertension and to construct a nomogram for predicting the occurrence of RH.

Methods and Results

A retrospective cohort study was conducted on 1635 patients initially diagnosed with hypertension at the Affiliated Traditional Chinese Medicine Hospital of Xinjiang Medical University from August 2019 to August 2021. Patients were followed up for a median of 31 months, with 373 cases (22.81%) developing RH. Least absolute shrinkage and selection operator regression and multivariable Cox regression analysis identified the TyG index as the strongest predictor of RH (hazard ratio, 5.472 [95% CI, 4.028–7.433];
P
<0.001). Consistent results were also observed in subgroup analyses across different ages and sexes. In addition to the TyG index, other independent risk factors, including uric acid, age, and the apnea‐hypopnea index, were noted. A nomogram model was subsequently developed using these risk factors, and including the TyG index notably enhanced the diagnostic effectiveness of the model in predicting the occurrence of RH.

Conclusions

The TyG index appears to be a potential predictor of RH in patients with hypertension, indicating that insulin resistance might be an important factor in the development and progression of RH.
Ischemic Stroke in Adults With Congenital Heart Disease: Cumulative Incidence and Associated Factors
Authors: Angerbjörn Maria , Johansson Bengt , Eriksson Marie , Rinnström Daniel , Sandberg Camilla , Christersson Christina , Sörensson Peder , Trzebiatowska‐Krzynska Aleksandra , Mandalenakis Zacharias , Thilén Ulf , Pennlert Johanna
Published: September 2024

Background

When more patients with congenital heart disease reach adult age, increased incidence of long‐term complications, including ischemic stroke, are expected. The aim of this study was to analyze cumulative incidence of ischemic stroke, associated factors, and case fatality in adult congenital heart disease.

Methods and Results

The study is based on Swedish national registers on congenital heart disease and stroke. Patients with congenital heart disease were followed between 2001 and 2018 for first‐ever ischemic stroke events (ischemic stroke due to patent foramen ovale excluded). Factors possibly associated with ischemic stroke were analyzed using Cox regression models. Out of 8914 adult patients with congenital heart disease, 108 suffered ischemic stroke over a mean period of 7.6±4.7 years. The mean age at ischemic stroke was 53.8 years, and the cumulative incidence was 0.15% at 1 year, 0.5% at 5 years, and 1.5% at 10 years. In multivariable analysis, age (hazard ratio [HR], 1.04 [95% CI, 1.03–1.06]), diabetes (HR, 2.9 [95% CI, 1.3–6.4]), ejection fraction <50% (HR, 1.9 [95% CI, 1.1–3.4]), atrial septal defect (HR, 3.0 [95% CI, 1.03–8.5]), and aortic valve lesions (HR, 4.8 [95% CI, 1.6–14.1]) were associated with increased risk. Among those with ischemic stroke, approximately half were on antithrombotic treatment (anticoagulants or antiplatelets) before admission. Case fatality was 6.5%.

Conclusions

The cumulative incidence of ischemic stroke was 1.5% after 10 years. In adult congenital heart disease, the type of heart lesion, diabetes, ejection fraction <50%, and age were important factors associated with ischemic stroke. Despite a relatively young age, mortality is a significant threat. At time of the ischemic stroke event, approximately half of the patients were on antithrombotic treatment.
Quantitative Electroencephalography for Predication of Neurological Dysfunction in Type A Aortic Dissection: A Prospective Observational Study
Authors: Wang Ya‐peng , Cheng Yong‐qing , Wang Hanghang , Wang Huanhuan , Liu Wen‐xue , Jiang Yi , Xue Yun‐xing , Chen Yang , Zhou Qing , Luo Xuan , Zhang Qingxiu , Qu Jason Zhensheng , Wang Dong‐jin
Published: September 2024

Background

Type A aortic dissection presents challenges with postoperative cerebral complications, and this study evaluates the predictive value of quantitative electroencephalography for perioperative brain function prognosis.

Methods and Results

Amplitude‐integrated electroencephalography (aEEG) processes raw signals through filtering, amplitude integration, and time compression, displaying the data in a semilogarithmic format. Using this method, postoperative relative band power (post‐RBP) α% and dynamic aEEG (ΔaEEG) grade were significantly associated with neurological dysfunction in univariate and multivariable analyses, with area under the receiver operating characteristic curve of 0.876 (95% CI, 0.825–0.926) for the combined model. Postoperative relative band power α% and ΔaEEG were significantly associated with adverse outcomes, with area under the receiver operating characteristic curve of 0.903 (95% CI, 0.835–0.971) for the combined model. Postoperative relative band power α% and ΔaEEG were significantly associated with transient neurological dysfunction and stroke, with areas under the receiver operating characteristic curve of 0.818 (95% CI, 0.760–0.876) and 0.868 (95% CI, 0.810–0.926) for transient neurological dysfunction, and 0.815 (95% CI, 0.743–0.886) and 0.831 (95% CI, 0.746–0.916) for stroke. Among 56 patients, the Alberta Stroke Program Early Computed Tomography score was superior to ΔaEEG in predicting neurological outcomes (area under the receiver operating characteristic curve of 0.872 versus 0.708 [95% CI, 0.633–0.783];
P
<0.05).

Conclusions

Perioperative quantitative electroencephalography monitoring offers valuable insights into brain function changes in patients with type A aortic dissection. ∆aEEG grades can aid in early detection of adverse outcomes, while postoperative relative band power and ∆aEEG grades predict transient neurological dysfunction. Quantitative electroencephalography can assist cardiac surgeons in assessing brain function and improving outcomes in patients with type A aortic dissection.

Registration

URL:
https://www.chictr.org.cn
; Unique identifier: ChiCTR2200055980.
Clinical Outcomes in Relation to Total Hospital Surgical and Transcatheter Aortic Valve Replacement Volumes
Authors: Elbadawi Ayman , Mohamed Amr , Sedhom Ramy , Garcia Lisardo , Pandey Ambarish , Girotra Saket , Bavry Anthony , Vemulapalli Sreekanth , Kumbhani Dharam J.
Published: September 2024

Background

There is a paucity of data regarding the relationship between overall hospital volumes for total aortic valve replacement (AVR; transcatheter AVR [TAVR] or surgical AVR [SAVR]) and patient outcomes.

Methods and Results

We queried the 2019 Nationwide Readmission Database for patients undergoing AVR. Based on procedural volumes of TAVR or SAVR, we classified hospitals as high (≥50th percentile) or low (<50th percentile) volume centers and categorized hospitals as high TAVR/high SAVR, high TAVR/low SAVR, high SAVR/low TAVR, and low TAVR/low SAVR. Multivariable regression models were employed. The main study outcomes were in‐hospital mortality and 30‐day readmission after total AVR. Our final analysis included 72 123 patients undergoing AVR at 400 hospitals across the United States. The median (interquartile range) hospital procedural volumes for total AVR, TAVR, and SAVR were 137 (86–210), 82 (50–127), and 56 (31–87) procedures, respectively. There was an inverse correlation between hospital procedural volumes of AVR, TAVR, or SAVR and in‐hospital mortality after total AVR but not with 30‐day readmission. Using high TAVR/high SAVR hospitals as reference, there was higher in‐hospital mortality after total AVR among low TAVR/low SAVR hospitals (adjusted odds ratio [OR], 1.29 [95% CI, 1.07–1.56]) but similar in‐hospital mortality among high TAVR/low SAVR hospitals and low TAVR/high SAVR volumes. There was no difference in 30‐day readmission rates after total AVR among the 4 hospital categories.

Conclusions

Nationwide data revealed that in‐hospital mortality after total AVR (SAVR or TAVR) is inversely related to hospital total volumes of AVR. Patients with aortic stenosis have better outcomes if they are managed among experienced centers with high case volumes of both TAVR and SAVR.
Risk of Traumatic Intracranial Hemorrhage After Stroke: A Nationwide Population‐Based Cohort Study in Taiwan
Authors: Fang Yun‐Ting , Liao Shu‐Fen , Chen Ping‐Ling , Yeh Tian‐Shin , Chen Chin‐I , Piravej Krisna , Wu Chia‐Chieh , Chiu Wen‐Ta , Lam Carlos
Published: September 2024

Background

Stroke and traumatic intracranial hemorrhage (tICH) are major causes of disability worldwide, with stroke exerting significant negative effects on the brain, potentially elevating tICH risk. In this study, we investigated tICH risk in stroke survivors.

Methods and Results

Using relevant data (2017–2019) from Taiwan's National Health Insurance Research Database, we conducted a population‐based retrospective cohort study. Patients were categorized into stroke and nonstroke groups, and tICH risk was compared using a Cox proportional‐hazards model. Among 164 628 patients with stroke, 1004 experienced tICH. Patients with stroke had a higher tICH risk than nonstroke counterparts (adjusted hazard ratio [HR], 3.49 [95% CI, 3.17–3.84]). Subgroup analysis by stroke type revealed higher tICH risk in hemorrhagic stroke survivors compared with ischemic stroke survivors (HR, 5.64 [95% CI, 4.97–6.39] versus 2.87 [95% CI, 2.58–3.18], respectively). Older patients (≥45 years) with stroke had a higher tICH risk compared with their younger counterparts (<45 years), in contrast to younger patients without stroke (HR, 7.89 [95% CI, 6.41–9.70] versus 4.44 [95% CI, 2.99–6.59], respectively). Dementia and Parkinson disease emerged as significant tICH risk factors (HR, 1.69 [95% CI, 1.44–2.00] versus 2.17 [95% CI, 1.71–2.75], respectively). In the stroke group, the highest tICH incidence density occurred 3 months after stroke, particularly in patients aged >65 years.

Conclusions

Stroke survivors, particularly those with hemorrhagic stroke and those aged ≥45 years, face elevated tICH risk. Interventions targeting the high‐risk period are vital, with fall injuries potentially contributing to tICH incidence.
Folate, Homocysteine, and Adverse Outcomes After Ischemic Stroke
Authors: Shi Mengyao , Zheng Jin , Liu Yang , Mao Xueyu , Wu Xuechun , Chu Min , Niu Huicong , Sun Lulu , Chang Xinyue , He Yu , Liu Yi , Guo Daoxia , Zhang Yonghong , Zhu Zhengbao , Zhao Jing
Published: September 2024

Background

As a risk factor of cardiovascular diseases, homocysteine can be effectively lowered by folate. However, the associations of folate and homocysteine levels with the prognosis of ischemic stroke remained unclear.

Methods and Results

A total of 3530 patients with ischemic stroke were included. Serum folate and homocysteine levels were measured at admission. The primary outcome was composite of death and major disability (modified Rankin Scale score≥3) at 3 months after stroke onset. Univariate and multivariate logistic regression models were used. The mediation effect of homocysteine was examined. During follow‐up, 1056 participants developed the primary outcome. In the univariate model, participants in the highest quartile of folate had a 29% (95% CI, 0.58–0.87) decreased risk of primary outcome compared with those in the lowest quartile. After multivariate adjustment, the odds ratio associated with the highest quartile of folate was 0.58 (95% CI, 0.46–0.73) for primary outcome. In contrast, participants in the highest quartile of homocysteine had a 52% (95% CI, 1.24–1.98) increased risk of primary outcome compared with those in the lowest quartile. After multivariate adjustment, the odds ratio associated with highest quartile of homocysteine was 1.57 (95% CI, 1.24–1.98) for primary outcome. In addition, 25.5% of the observed associations between folate and primary outcome was mediated through homocysteine (
P
=0.012).

Conclusions

High folate levels were associated with low risks of death and major disability among Chinese patients with ischemic stroke, and homocysteine partially mediated the observed potential beneficial role of folate.
Exercise Alleviates Cardiovascular Diseases by Improving Mitochondrial Homeostasis
Authors: Zhang Huijie , Zhang Yuxuan , Zhang Jiaqiao , Jia Dandan
Published: September 2024

Engaging in regular exercise and physical activity contributes to delaying the onset of cardiovascular diseases (CVDs). However, the physiological mechanisms underlying the benefits of regular exercise or physical activity in CVDs remain unclear. The disruption of mitochondrial homeostasis is implicated in the pathological process of CVDs. Exercise training effectively delays the onset and progression of CVDs by significantly ameliorating the disruption of mitochondrial homeostasis. This includes improving mitochondrial biogenesis, increasing mitochondrial fusion, decreasing mitochondrial fission, promoting mitophagy, and mitigating mitochondrial morphology and function. This review provides a comprehensive overview of the benefits of physical exercise in the context of CVDs, establishing a connection between the disruption of mitochondrial homeostasis and the onset of these conditions. Through a detailed examination of the underlying molecular mechanisms within mitochondria, the study illuminates how exercise can provide innovative perspectives for future therapies for CVDs.
Typifications in Epidendrum species (Laeliinae, Orchidaceae) endemic to Brazil
Authors: PESSOA EDLLEY M. , ZOCAL KELVIN H. , FEITOZA LUCAS H.J. , RONDON-ANJOS MARCOS V. , PINHO MAX F. , RIBEIRO MURILO G. , CABRAL THAINÁ P.S. , KOCH ANA K.
Published: September 2024

During ongoing studies of the Brazilian species of Epidendrum, we determined that some names needed formal typification. Lectotypes for E. brevicolle, E. caldense, E. campestre, E. cinnabarinum, E. cooperianum E. goebelii, E. henschenii, E. longispathum, E. longispathum, E. paulense, E. revolutum, and E. setiferum, and an epitype for E. cooperianum are designated here. We provide discussions of the history of the names linked to each species.
A new name Maesa sleumeri for Maesa lineolata Sleumer and lectotypification of Maesa lineolata H.R. Fletcher (Primulaceae)
Authors: DEVANATHAN KRISHANAMOORTHY , DHATCHANAMOORTHY NARAYANASAMY
Published: September 2024

N/A
Equity and Environmental Hazards: Intersections Across the United States and Associated Territories
Authors: Herrera Isabella
Published: September 2024

The United States and its associated territories uniquely experience challenges in weather, water, and climate (WWC); equity, inclusion, and justice (EIJ); and the intersection of WWC and EIJ, though these issues are not exclusive to any one state or territory and often transcend geographic and political boundaries. Socioeconomic and WWC vulnerabilities are inextricably linked, and historically underserved communities are disproportionately impacted by climate and weather hazards. This study by the American Meteorological Society (AMS) Policy Program aims to 1) identify key challenges and opportunities in weather, water, and climate for the United States and associated territories; 2) assess issues and potential areas for the advancement of equity, inclusion, and justice; and 3) develop a database of challenges and opportunities in WWC and/or EIJ within each respective U.S. state or territory.
Climatic significance of clay minerals in Cenozoic marine and lacustrine sediments
Authors: Fagel Nathalie
Published: September 2024

In sediments, clay minerals are mainly detrital. Formed by continental weathering, they are carried by surface transport predominantly by rivers, glaciers and, to a lesser extent, winds to the adjacent sedimentary basins and then are redistributed by oceanic currents. In a sedimentary core, the variability in the clay mineral assemblages reflects either variable physical and chemical weathering conditions in the watershed, typically with a significant link to climatic conditions, or changes in the mineral source, the latter being associated with various transport agents. When different sources are involved, a combination of mineralogical and geochemical proxies allows us to trace the detrital provenance, but they also indirectly provide valuable information on transport pathways and palaeocurrents. This manuscript reviews several examples from the literature and ongoing research on clay mineral variability in marine or lacustrine sedimentary records and interprets them in terms of: (1) climate control at different timescales, from the Neogene to the Quaternary; and (2) transport paths. Examples are selected to review the various clay-derived proxies in existence.
Navigating therapeutic challenges in VEXAS syndrome: exploring IL-6 and JAK inhibitors at the forefront
Authors: Li Xiao Xiao , Huang Wen Hui , Yang Xiao Bin , Yang Qi Lin , Zheng Yu , Huo Yong Bao , Xie Ting Ting , Huang Cheng Hui , Yu Shui Lian
Published: September 2024

VEXAS syndrome, an uncommon yet severe autoimmune disorder stemming from a mutation in the UBA1 gene, is the focus of this paper. The overview encompasses its discovery, epidemiological traits, genetic underpinnings, and clinical presentations. Delving into whether distinct genotypes yield varied clinical phenotypes in VEXAS patients, and the consequent adjustment of treatment strategies based on genotypic and clinical profiles necessitates thorough exploration within the clinical realm. Additionally, the current therapeutic landscape and future outlook are examined, with particular attention to the potential therapeutic roles of IL-6 inhibitors and JAK inhibitors, alongside an elucidation of prevailing limitations and avenues for further research. This study contributes essential theoretical groundwork and clinical insights for both diagnosing and managing VEXAS syndrome.
Lactic acid bacteria isolated from women’ breast milk and infants’ faeces have appreciable immunogenic and probiotic potentials against diarrheagenic E. coli strains
Authors: Obisesan Abiola O. , Abiodun Oyindamola O. , Ayeni Funmilola A.
Published: September 2024

Diarrheal diseases remain the leading cause of high mortality among the infants, particularly in the developing countries; Probiotic intervention for diarrhea has been an ongoing novel approach to diarrheal prevention and treatment. This study aims to characterize immunogenic and probiotic properties of lactic acid bacteria (LAB) isolated from human breast milk and neonates’ faeces. The LAB isolates from 16 mothers’ breast milk and 13 infants’ faeces were screened and identified by 16 S rRNA gene partial sequencing. Their antimicrobial activities against 5 strains of diarrheagenic Escherichia coli were tested. Organic acids production was quantified by HPLC, and antibiotic resistance pattern were determined by VITEK®. Autoaggregation, co-aggregation and hydrophobicity properties were assessed by UV spectrophotometry and immunomodulatory effect was determined in mouse model. Ninety-three LAB of five genera were identified. The most abundant species was Lactiplantibacillus plantarum with inhibition zones ranged from 8.0 to 25.0 ± 1 mm. Lacticaseibacillus rhamnosus A012 had 76.8 mg/mL lactic acid, (the highest concentration), was susceptible to all antibiotics tested. L. plantarum A011 and L. rhamnosus A012 were highly resistance to gastrointestinal conditions. L. rhamnosus A012 produced hydrophobicity of 25.01% (n-hexadecane), 15.4% (xylene) and its autoaggregation was 32.52%. L. rhamnosus A012 and L. plantarum A011 exert immunomodulatory effects on the cyclophosphamide-treated mice by upregulating anti-inflammatory cytokine and downregulating proinflammatory cytokines. Lactobacillus sp. demonstrated good probiotic and immunomodulatory properties. Further works are ongoing on the practical use of the strains.
A mixed methods study on poisoning and injury-related emergency department visits associated with opioids in Canada, 2011 to 2022: from the Canadian hospitals injury reporting and prevention program
Authors: Yao Xiaoquan , Rama Alyssa-Ann , Mazzitelli Julianna , McFaull Steven R. , Thompson Wendy
Published: September 2024

Background

The opioid crisis is a serious public health issue in Canada. There have been many surveillance programs and research studies on opioid-related emergency department (ED) visits at a national, provincial, regional or municipal level. However, no published studies have investigated the in-depth contexts surrounding opioid-related ED visits. In addition, few studies have examined injuries other than poisonings in those visits. The objective of this study is to investigate the contextual factors and co-occurrence of poisonings and injuries among the opioid-related ED visits in a Canadian sentinel surveillance system on injuries and poisonings from 2011 to 2022.

Methods

This study used a mixed methods design. The data source was the Canadian Hospitals Injury Reporting and Prevention Program. We first selected all opioid-related ED visits during our study period and then identified the contextual factors through a content analysis of the combination of the narrative description and other variables in the patients’ records. The contextual factors were organized into themes as opioid use context, social resource utilization, bystander involvement, and prior naloxone use. The opioid use context was used as a co-variable to examine the other themes and ED presentations (poisonings and other injuries). Quantitative descriptive approach was used to analyze all the contexts and ED presentations.

Results

The most common opioid use context was non-prescribed opioid use without intention to cause harm, followed by self-poisoning, children’s exposure, and medication error. Various rare contexts occurred. Paramedics participated in 27.9% of visits. Police and security guards were involved in 5.1% and 2.3% of visits, respectively. Child welfare or social workers were involved in 0.4% of visits. Bystanders initiated 18.9% of the ED visits. Naloxone use before arriving at the ED occurred in 23.4% of the visits with a variety of administrators. The majority of patients presented with poisoning effects, either with poisoning effects only or with other injuries or conditions.

Conclusions

Our study has provided an in-depth analysis of contextual factors and co-occurrence of poisonings and injuries among opioid-related ED visits in Canada. This information is important for ED programming and opioid-related poisoning and injury intervention and prevention.
Virtual reality education on myalgic encephalomyelitis for medical students and healthcare professionals: a pilot study
Authors: Anderson Tara , Duffy Grace , Corry Dagmar
Published: September 2024

Introduction

Myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS) is a chronic condition which may be characterised by debilitating fatigue, post-exertional malaise, unrefreshing sleep, and cognitive difficulties. ME/CFS has significant negative impact on quality of life for those living with the condition. This may be exacerbated by a lack of knowledge within healthcare regarding the condition. Previous research has found that immersive virtual reality (VR) educational experiences within healthcare education can increase knowledge and empathy.

Methods

The present study employed a quasi-experimental pre-test-post-test design to investigate the impact of a short immersive VR educational experience on knowledge of ME/CFS and empathy for those living with the condition. The VR experience placed participants into a virtual scene which told real life stories of the experience of people living with ME/CFS and their families. 43 participants completed in this pilot study: 28 medical students and 15 primary care health professionals. Participants completed measures of knowledge of ME/CFS and empathy before and after engagement with the experience.

Results

A statistically significant increase was found for levels of knowledge (p < .001, d = 0.74) and empathy (p < .001, d = 1.56) from pre-VR experience levels to post-VR experience levels with a medium and large effect size, respectively. Further analysis revealed no statistically significant difference between baseline levels of knowledge of ME/CFS between healthcare professionals and medical students.

Discussion

The present study is the first to explore the use of this short immersive VR experience as an education tool within healthcare to increase knowledge of ME/CFS, and empathy for those living with the condition. Findings allude to the previously established lack of knowledge of ME/CFS within healthcare although promisingly the increases in knowledge and empathy found suggest that this immersive VR experience has potential to address this. Such changes found in this small-scale pilot study suggest that future research into the use of VR as an educational tool within this setting may be beneficial. Use of a control group, and larger sample size as well as investigation of retention of these changes may also enhance future research.
No medication prescription and residential distance from the hospital are important factors associated with nonsurgical weight-loss treatment discontinuance in Japanese patients with high-degree obesity: a retrospective study
Authors: Ohira Masahiro , Tsuji Sayaka , Watanabe Yasuhiro , Abe Kazuki , Yamaoka Shuhei , Nakamura Shoko , Oka Rena , Tanaka Shou , Kawagoe Naoyuki , Yamaguchi Takashi , Nagayama Daiji , Tatsuno Ichiro , Saiki Atsuhito
Published: September 2024

Background

Although the percentage of the population with a high degree of obesity (body mass index [BMI] ≥ 35 kg/m2) is low in Japan, the prevalence of obesity-related diseases in patients with high-degree obesity is greater than that in patients with a BMI < 35 kg/m2. Therefore, treatment for high-degree obesity is important. However, clinical studies have reported that 20–50% of patients with obesity discontinue weight-loss treatment in other countries. The circumstances surrounding antiobesity agents are quite different between Japan and other countries. In this study, we investigated the predictors of treatment discontinuation in Japanese patients with high-degree obesity.

Methods

We retrospectively reviewed the medical charts of 271 Japanese patients with high-degree obesity who presented at Toho University Sakura Medical Center for obesity treatment between April 1, 2014, and December 31, 2017. The patients were divided into non-dropout and dropout groups. Patients who discontinued weight-loss treatment within 24 months of the first visit were defined as “dropouts.” Multivariate Cox proportional hazards regression analysis and Kaplan–Meier survival analysis were performed to examine the factors predicting treatment withdrawal.

Results

Among the 271 patients, 119 (43.9%) discontinued treatment within 24 months of the first visit. The decrease in BMI did not significantly differ between the two groups. No prescription of medication and residential distance from the hospital exceeding 15 km were the top contributors to treatment discontinuation, and the absence of prescription medication was the most important factor. The dropout-free rate was significantly higher in patients with medication prescriptions than in those without and in patients who lived within 15 km of the hospital than in those who lived farther than 15 km from the hospital.

Conclusions

No medication prescription and longer residential distance from the hospital were associated with treatment dropout in Japanese patients with high-degree obesity; therefore, the addition of antiobesity medications and telemedicine may be necessary to prevent treatment discontinuation in such patients.
Truncated mini LRP1 transports cargo from luminal to basolateral side across the blood brain barrier
Authors: Fritzen Laura , Wienken Katharina , Wagner Lelia , Kurtyka Magdalena , Vogel Katharina , Körbelin Jakob , Weggen Sascha , Fricker Gert , Pietrzik Claus U.
Published: September 2024

Background

The most crucial area to focus on when thinking of novel pathways for drug delivery into the CNS is the blood brain barrier (BBB). A number of nanoparticulate formulations have been shown in earlier research to target receptors at the BBB and transport therapeutics into the CNS. However, no mechanism for CNS entrance and movement throughout the CNS parenchyma has been proposed yet. Here, the truncated mini low-density lipoprotein receptor-related protein 1 mLRP1_DIV* was presented as blood to brain transport carrier, exemplified by antibodies and immunoliposomes using a systematic approach to screen the receptor and its ligands’ route across endothelial cells in vitro.

Methods

The use of mLRP1_DIV* as liposomal carrier into the CNS was validated based on internalization and transport assays across an in vitro model of the BBB using hcMEC/D3 and bEnd.3 cells. Trafficking routes of mLRP1_DIV* and corresponding cargo across endothelial cells were analyzed using immunofluorescence. Modulation of γ-secretase activity by immunoliposomes loaded with the γ-secretase modulator BB25 was investigated in co-cultures of bEnd.3 mLRP1_DIV* cells and CHO cells overexpressing human amyloid precursor protein (APP) and presenilin 1 (PSEN1).

Results

We showed that while expressed in vitro, mLRP1_DIV* transports both, antibodies and functionalized immunoliposomes from luminal to basolateral side across an in vitro model of the BBB, followed by their mLRP1_DIV* dependent release of the cargo. Importantly, functionalized liposomes loaded with the γ-secretase modulator BB25 were demonstrated to effectively reduce toxic Aß42 peptide levels after mLRP1_DIV* mediated transport across a co-cultured endothelial monolayer.

Conclusion

Together, the data strongly suggest mLRP1_DIV* as a promising tool for drug delivery into the CNS, as it allows a straight transport of cargo from luminal to abluminal side across an endothelial monolayer and it’s release into brain parenchyma in vitro, where it exhibits its intended therapeutic effect.
Severe pancytopenia at the presentation of Imerslund-Gräsbeck syndrome in a 23-month-old Italian boy
Authors: Di Sario Francesca , Piloni Francesca , Gasparini Francesco , Serpetti Eleonora , Bruschi Barbara , Coccia Paola , Lionetti Maria Elena , Gatti Simona
Published: September 2024

Background

Imerslund-Gräsbeck syndrome (IGS) is a rare autosomal recessive disorder characterized by megaloblastic anemia due to selective cobalamin malabsorption and benign proteinuria. IGS is caused by a disfunction of the cubam receptor, which mediates the reabsorption of cobalamin in the ileum and the reuptake of albumin in renal proximal tubules.

Case presentation

We describe the case of a 23-month-old-italian infant presenting with severe pancytopenia and failure to thrive in whom the diagnosis of IGS was made and vitamin B12 replacement therapy was resolutive. Genetic analysis (NGS with CNV analysis including 214 genes involved in bone marrow failure and anemia), showed the presence of two pathogenetic variants in the AMN gene (c-208–2 A > G and c.1006 + 34_1007-31del). These variants have been previously described in the literature, but their combination has never been reported.

Conclusions

Imerslund-Gräsbeck syndrome should be considered in the differential diagnosis of children with severe pancytopenia even in those without neurological involvement. This case emphasizes the importance of an early diagnosis and prompt treatment, to prevent irreversible neurological injury.
Should my child be given antibiotics? A systematic review of parental decision making in rural and remote locations
Authors: Marsh Stephanie A. , Parsafar Sara , Byrne Mitchell K.
Published: September 2024

Background

The emergence and growth in antibiotic resistant bacteria is a critical public health problem exacerbated by the misuse of antibiotics. Children frequently succumb to illness and are often treated with antibiotic medicines which may be used improperly by the parent. There is limited evidence of the factors influencing parental decision-making about the use of antibiotics in low-resource contexts. The aim of this systematic review was to understand and describe how parents living in rural and remote locations make choices about their children’s antibiotic use.

Method

The CINAHL, Web of Science, Medline, Scopus and Academic Search Premier databases were systematically searched from 31 January until 28 June in 2023. No date restrictions were applied and additional search methods were utilised to identify further studies that met inclusion criteria. Eligibility criteria included studies which reported on factors contributing to parental decisions about their children’s use of antibiotics in rural and remote settings. The Joanna Briggs Institute Critical Appraisal Checklists were employed to evaluate studies. Characteristics and findings were extracted from studies, and data was synthesised descriptively and presented in summary tables.

Results

A total of 3827 articles were screened and 25 worldwide studies comprising of quantitative, qualitative and prospective designs were included in the review. Studies that reported the number of rural caregivers consisted of 12 143 participants. Data analysis produced six broad themes representing the mechanisms that influenced parents in their access and use of antibiotics: the child’s symptoms; external advice and influences; parent-related determinants; barriers to healthcare; access to antibiotics; and socio-demographic characteristics.

Conclusions

A number of factors that influence parents’ prudent use of antibiotics in rural contexts were identified. In seeking to enhance appropriate use of antibiotics by parents in rural and remote settings, these determinants can serve to inform interventions. However, the identified studies all relied upon parental self-reports and not all studies reviewed reported survey validation. Further research incorporating validated measures and intervention strategies is required.

Registration details

Should my child be given antibiotics? A systematic review of parental decision making in rural and remote locations; CRD42023382169; 29 January 2023 (date of registration). Available from PROSPERO.
Clinical efficacy and safety of faecal microbiota transplantation in the treatment of irritable bowel syndrome: a systematic review, meta-analysis and trial sequential analysis
Authors: Lo Shao-Wei , Hung Tsung-Hsuan , Lin Yen-Tsen , Lee Chun-Shen , Chen Chiung-Yu , Fang Ching-Ju , Lai Pei-Chun
Published: September 2024

Background

The aim of this study is to evaluate the efficacy and safety of faecal microbiota transplantation (FMT) for the treatment of irritable bowel syndrome (IBS).

Methods

We searched four databases for randomised controlled trials (RCTs) that compared FMT with a control intervention in patients with IBS. The revised Cochrane risk-of-bias (RoB) tool was chosen for appraisal. Meta-analysis with trial sequential analysis (TSA) was conducted. Grading of Recommendations Assessment Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence (CoE).

Results

We included 12 RCTs with a total of 615 participants. Meta-analyses showed no significant difference between the FMT and control groups in terms of clinical responses (relative risk [RR] = 1.44, 95% confidence interval [CI] 0.88–2.33) and changes in IBS Severity Scoring System (IBS-SSS) scores (standardised mean difference [SMD] =  − 0.31, 95% CI  − 0.72 to 0.09) and IBS Quality of Life (IBS-QOL) scores (SMD = 0.30, 95% CI  − 0.09 to 0.69). Subgroup analysis revealed that in studies with low RoB and using endoscopy, nasojejunal tube and rectal enema delivery, FMT led to a significant improvement in clinical responses and changes in IBS-SSS and IBS-QOL scores. TSA suggested that the current evidence is inconclusive and that the CoE is very low.

Conclusion

This study suggests that patients with IBS may benefit from FMT especially when it is administered via endoscopy, nasojejunal tube or rectal enema. However, the certainty of evidence is very low. Further research is needed to confirm the efficacy and safety of FMT for IBS treatment.

Trial Registration: PROSPERO registration number CRD42020211002.
Immune-related [18F]FDG PET findings in patients undergoing checkpoint inhibitors treatment: correlation with clinical adverse events and prognostic implications
Authors: Santo Giulia , Cucè Maria , Restuccia Antonino , Del Giudice Teresa , Tassone Pierfrancesco , Cicone Francesco , Tagliaferri Pierosandro , Cascini Giuseppe Lucio
Published: September 2024

Background

Direct comparisons between [18F]FDG PET/CT findings and clinical occurrence of immune-related adverse events (irAEs) based on independent assessments of clinical and imaging features in patients receiving immune checkpoint inhibitors (ICIs) are missing. Our aim was to estimate sites, frequency, and timing of immune-related PET findings during ICIs treatment in patients with melanoma and NSCLC, and to assess their correlation with clinical irAEs. Prognostic implications of immune-related events were also investigated.

Methods

Fifty-one patients with melanoma (47%) or NSCLC (53%) undergoing multiple PET examinations during anti-PD1/PDL1 treatment were retrospectively included. Clinical irAEs were graded according to CTCAE v.5.0. Abnormal PET findings suggestive of immune activation were described by two readers blinded to the clinical data. Progression-free survival (PFS) and overall survival (OS) were analyzed with the Kaplan-Meier method in patients stratified according to the presence of irAEs, immune-related PET findings or both.

Results

Twenty-one patients showed clinical irAEs only (n = 6), immune-related PET findings only (n = 6), or both (n = 9). In patients whose imaging findings corresponded to clinical irAEs (n = 7), a positive correlation between SUVmax and the severity of the clinical event was observed (rs=0.763, p = 0.046). Clinical irAEs occurred more frequently in patients without macroscopic disease than in metastatic patients (55% vs. 23%, p = 0.039). Patients who developed clinical irAEs had a significantly longer PFS than patients who remained clinically asymptomatic, both in the overall cohort (p = 0.011) and in the subgroup of (n = 35) patients with metastatic disease (p = 0.019). The occurrence of immune-related PET findings significantly stratified PFS in the overall cohort (p = 0.040), and slightly missed statistical significance in patients with metastatic disease (p = 0.08). The best stratification of PFS was achieved when all patients who developed immune-related events, either clinically relevant or detected by PET only, were grouped together both in the overall cohort (p = 0.002) and in patients with metastatic disease (p = 0.004). In the whole sample, OS was longer in patients who developed any immune-related events (p = 0.032).

Conclusion

Patients with melanoma or NSCLC under ICI treatment can develop clinical irAEs, immune-related PET findings, or both. The occurrence of immune-related events has a prognostic impact. Combining clinical information with PET assessment improved outcome stratification.
Impact of ante-mortem fluoxetine administration on estimation of post-mortem interval and insect activity in rabbit carcasses
Authors: Saleh Fatema M. , Badawy Assem H. , Badawy Rawda M. , Rahman Asmaa Abdel , Adly Eslam
Published: September 2024

Background

Increasing the number of drug-related deaths has affected medico-legal death investigations. Drugs within a corpse have a great impact on the insects’ development rate which in turn will affect the rate of post-mortem decomposition and the estimation of the post-mortem interval. This explains the importance of the application of forensic entomotoxicology, which studies the impact of drugs and toxins on the development and succession patterns of insects. The current study aimed to determine the impact of fluoxetine, one of the selective serotonin reuptake inhibitors (SSRIs), on post-mortem decomposition, insects’ attraction, and its pattern of succession on carcasses. Sixteen healthy male and female Oryctolagus cuniculus rabbits were chosen to be included in this study. They were divided into a treated group of eight rabbits received oral fluoxetine for 28 days and a control group of eight rabbits received oral distilled water for 28 days. After oral administration of 10 mg/kg/day of fluoxetine and distilled water for 28 days, rabbits were sacrificed, and carcasses were transmitted to the roof of Research and Training Centre on Vectors of Diseases at faculty of Sciences, Ain Shams University, for following up the post-mortem decomposition process and insect’s attraction to carcasses for 60 days. Carcasses were put in two outdoor sites that differ in temperature to assess the effect of temperature on decomposition process.

Results

Fluoxetine administration has accelerated the rate of post-mortem decomposition in the treated carcasses by 3–9 days compared to the control ones and affected the numbers and species of attracted insects, while it had no effect on the insects’ succession patterns. Exposure of carcasses to direct sunlight has accelerated the rate of decomposition in comparison to that of carcasses put in shade in the overall period of decomposition by about 14 to 16 days.

Conclusions

Fluoxetine has an important and effective role in post-mortem decomposition and estimation of post-mortem interval (PMI) and has a great impact on attracted insects to the treated carcasses. Temperature has a great effect on the rate of decomposition of carcasses. Higher temperature accelerates the rate of post-mortem decomposition.
A systematic review of sofosbuvir/velpatasvir/voxilaprevir in HCV patients previously treated with direct-acting antivirals
Authors: Rustam Rehan , Qaisar Aqsa
Published: September 2024

The importance of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) remains crucial in managing chronic HCV infection among patients who have experienced treatment failure and relapse after prior use of direct-acting antivirals (DAAs), as evidenced by high SVR12. However, limited real-world data exists on safety and efficacy. Therefore, the study’s goal was to conduct a qualitative systematic review to assess SOF/VEL/VOX’s effectiveness and safety. Thorough searches spanned PubMed, Embase, and Scopus, from 2015 to August 1st, 2023. The outcomes assessed were SVR12 and treatment-related adverse events (AEs). We identified and analyzed 12 studies in which SVR12 of the per-protocol (PP) population was 96.7% and of the intention-to-treat (ITT) population was 92.6% showing excellent efficacy of SOF/VEL/VOX. SVR12 rates notably differed among patients: those without GT3 infection (94.20%) and without cirrhosis (97.60%) experienced higher rates compared to patients having GT3 infection (87.40%) and cirrhotic patients (94.20%). Treatment-related AEs were also recorded. To summarize, our study presents evidence that SOF/VEL/VOX serves as an extremely safe and efficacious therapy for HCV-infected patients, previously treated with DAAs.
The Moral Hazards of Technical Debt in Large Language Models: Why Moving Fast and Breaking Things Is Bad
Authors: Vee Annette
Published: September 2024

Companies such as OpenAI and other tech start-ups often pass on “technical debt” to consumers—that is, they roll out undertested software so that users can discover errors and problems. The breakneck pace of our current AI “arms race” implicitly encourages this practice and has resulted in consumer-facing large language models (LLMs) that have problems with bias and truth and unclear social implications. Yet, once the models are out, they are rarely retracted. The result of passing on the technical debt of LLMs to users is a “moral hazard,” where companies are incentivized to take greater risks because they do not bear their full cost. The concepts of technical debt and moral hazards help to explain the dangers of LLMs to society and underscore a need for a critical approach to AI to balance the ledger of AI risks.
Harriet Tubman's Deep Voice
Authors: Wallace Maurice , Peeler Matthew
Published: September 2024

The authors suggest that national investment in the educational utility of automated software comes at an enormous cost, a price paid by the very students that technology aims to convert to history as a lively and accessible field. This “high-tech mimicry” pretends to incarnate the past but instead silences the inflections of time, gender, region, race, or other vocalic variables. Further, the perception that technology is objective or unbiased conceals the vulnerabilities of language models. The authors argue that the illusions of authenticity these bots produce does not bode well for teaching African American history.
The Origins of Generative AI in Transcription and Machine Translation, and Why That Matters
Authors: Stone Matthew , Goodlad Lauren M. E. , Sammons Mark
Published: September 2024

In this essay, written in dialogue with the introduction to this special issue, the authors offer a critical history of the development of large language models (LLMs). The essay's goal is to clearly explicate their functionalities and illuminate the effects of their “generative” capacities—particularly the troubling divergences between how these models came into being, how they are currently developed, and how they are marketed. The evolution of LLMs and of their deployment as chatbots was not rooted in the design of interactive systems or in robust frameworks for humanlike communication or information access. Instead LLMs—in particular, generative pretrained transformers (GPTs)—arose through the steady advance of statistical proxies for predicting the plausibility of automated transcriptions and translations. Buoyed by their increasing faith in scale and “data positivism,” researchers adapted these powerful models for the probabilistic scoring of text to chat interaction and other “generative” applications—even though the models generate convincingly humanlike output without any means of tracking its provenance or ensuring its veracity. The authors contrast this technical trajectory with other intellectual currents in AI research that aimed to create empowering tools to help users to accomplish explicit goals by augmenting their capabilities to think, act, and communicate, through mechanisms that were transparent and accountable. The comparison to this “road not taken” positions the weaknesses of LLMs, chatbots, and LLM-based digital assistants—including their well-known “misalignment” with helpful and safe human use—as a reflection of developers’ failure to conceptualize and pursue their ambitions for intelligent assistance as responsible to and engaged with a broader public.
E depois das eleições?
Authors: Wilner Adriana
Published: September 2024

O que esperar das novas prefeitas e dos novos prefeitos? Em um cenário político polarizado, o debate é dominado por temas pouco relevantes para o bom funcionamento das cidades, mas que repercutem nas redes sociais. Passado o pleito, entretanto, eleitas(os) terão que se deparar com a realidade: os municípios enfrentam o desafio de gerenciar crescentes atribuições, com autonomia limitada para acessar recursos.