bluuebunny/crossref_metadata_2025 huggingface dataset:
QT Prolongation Associated with Administration of Bedaquiline, a Novel Anti-Tuberculosis Drug
Authors: Gavras Nicholas , Schluger Neil W.
Published: October 2024

Bedaquiline is a diarylquinoline compound that has recently been introduced and approved for use in the treatment of multidrug-resistant tuberculosis (MDR-TB). Its mechanism of action is inhibition of adenosine triphosphate-synthase. In combination with other antibiotics, bedaquiline-containing regimens administered for 6 months achieve cure rates of roughly 90%, in contrast to the previously used, 24-month-long WHO-recommended regimens for the treatment of MDR-TB. However, since its introduction, concerns have been raised about its effects on QT prolongation and its safety in routine clinical use. We reviewed the published experience regarding bedaquiline use, QT prolongation, and adverse cardiac events when the drug was used alone or in combination. Overall, data are reassuring that bedaquiline use in clinical practice is not associated with an excess of cardiac deaths or other clinically meaningful cardiac events. This review provides reassurance and support for the continued use of bedaquiline in the treatment of MDR-TB.
Revolutionizing Cardiac Care: The Role of Gene Therapy in Treating Cardiomyopathy
Authors: Desai Dev , Maheta Darshil Kumar , Agrawal Siddharth Pravin , Patel Monit , Frishman William H. , Aronow Wilbert S.
Published: October 2024

Gene therapy presents a method for addressing types of cardiomyopathies that play a substantial role in heart failure. This innovative approach, leveraging technologies such as clustered regularly interspaced short palindromic repeats/Cas9 for modifying genomes, holds promise for lasting treatments or potential cures that go beyond therapies. It is essential to grasp the workings of gene therapy, including gene silencing, clustered regularly interspaced short palindromic repeats genome editing, and enhancing sarcomere function to effectively apply it to treating cardiomyopathy. Examining current trials will shed light on the advancements and accomplishments in this field while also addressing the obstacles, uncertainties, and opportunities ahead. Delving into the possibilities of gene therapy involves exploring targets and inventive delivery methods that underscore the evolving landscape of research in this domain hinting at a future brimming with opportunities to transform care. The progress made in using gene therapy to treat cardiomyopathies represents the progress of medicine in driving forward scientific innovation to provide more precise and enduring solutions for patients. Continuously refining gene therapy techniques and deepening our knowledge of genetics are factors that will shape the future direction of cardiac care. The potential of gene therapy does not just benefit individuals with cardiomyopathy but also represents a move toward effective treatments for various genetic conditions. This signifies a step in the pursuit of holistic healthcare solutions.
The First Triple Agonist for Antiobesity: Retatrutide
Authors: Tetelbaun Lauren , Mullally Jamie A. , Frishman William H.
Published: October 2024

The prevalence of individuals with overweight and obesity has increased by 18% since 1990 and it is projected that by 2030, nearly 50% of US adults will have obesity. Lifestyle modifications, such as diet and exercise, typically lead to approximately 3–5% weight loss, whereas 5–15% weight loss is necessary to significantly impact obesity-associated comorbidities and improve overall health outcomes. In addition to lifestyle modifications, pharmacotherapy has been utilized as an adjunctive treatment to increase weight loss and improve health outcomes. The Food and Drug Administration has currently approved 6 drugs to treat overweight and obesity, with the recently approved drugs surging in popularity after demonstrating superior weight loss outcomes. Additionally, a number of agents are in the pipeline, offering promise of unprecedented degrees of weight loss. One such drug is retatrutide, which is a triple agonist targeting the glucagon-like peptide-1 receptor (GLP-1R), glucose-dependent insulinotropic polypeptide receptor, and glucagon receptor. Phase 1 and 2 clinical trials have demonstrated the safety, tolerability, and pharmacokinetics of retatrutide in patients with obesity and/or type 2 diabetes. The pharmacokinetics of retatrutide were dose proportional and its mean half-life of approximately 6 days supported a once-weekly dosing. The safety profile was similar to GLP-1R agonists and glucose-dependent insulinotropic polypeptide receptor/GLP-1R co-agonists, with gastrointestinal disorders being the most common adverse effects reported. Each trial demonstrated greater weight loss with retatrutide treatment in comparison to placebo, with greatest efficacy at higher doses. Overall, these clinical trials have demonstrated the superior efficacy of retatrutide as a weight loss medication in patients with overweight and obesity.
Scar-Related Ventricular Tachycardia: Pathophysiology, Diagnosis, and Management
Authors: Biswas Ratnadeep , Kapoor Abhay , Maheta Darshilkumar , Agrawal Siddharth Pravin , Mendha Akash , Frishman William H. , Aronow Wilbert S.
Published: October 2024

Scar-related ventricular tachycardia (VT) commonly results from scarring in the myocardium, principally produced by antecedent myocardial infarction, cardiomyopathy, or prior cardiac surgery. The resultant arrhythmogenic substrate from scarred tissue and the alteration of normal cardiac electrical conduction predispose patients to reentrant circuits, followed by VT. This literature review synthesizes current research on pathophysiology, diagnostic methods, and treatment modalities of scar-related VT. The primary contents of the review are descriptions of the mechanisms through which myocardial fibrosis results in VT, clinical presentations of the condition, and advanced diagnostic techniques, including electrophysiological studies and mapping. Furthermore, the review outlines the various management strategies, such as implantable cardioverter-defibrillators, catheter ablation, stereotactic arrhythmia radioablation, and surgical ablation. The discussion also includes emerging therapeutics, such as gene therapy, artificial intelligence, and precision medicine in managing scar-related VT, emphasizing the ongoing advancements aimed at improving patient outcomes.
Nocebo Effect on Pain Perception and Attention with Children With and Without Attention Deficit And/Or Hyperactivity Disorder
Authors: Belleï-Rodriguez Carmen-Édith , Colloca Luana , Lorrain Dominique , Marchand Serge , Léonard Guillaume
Published: October 2024

Objective:

Attention deficit disorder with or without hyperactivity (ADHD) has negative consequences for children. The effectiveness of medical interventions and educational outcomes are strongly influenced by expectations, which can be modulated by nocebo effects. The aims of this study were to compare the nocebo effect on pain perception and attention in children with and without ADHD as well as to characterize the associations of the nocebo effect with personal variables, such as anxiety, sleep, and pain catastrophizing.

Methods:

Data were collected from 30 children with and without ADHD. The nocebo effect was induced using an inactive pill, “increasing” pain perception and attention deficits. Experimental thermal pain was evoked using a thermode and recorded using a computerized visual analog scale. Attention abilities were measured with the Stop-Signal Task. We also used questionnaires to measure personal variables.

Results:

When combining groups, the nocebo treatment led to comparable nocebo effects for pain (increased pain perception) and attention (increased time needed for inhibition). When comparing groups, the nocebo effect on pain perception was similar for children with and without ADHD. Inattention, learning problems, anxiety, and sleep problems were associated with the nocebo response for pain and attention.

Conclusion:

This exploratory study conducted in an experimental setting emphasizes the importance of managing children's expectations for pain perception and attention as well as the potentially deleterious impact of negative suggestions on elementary school children.
Nonpharmaceutical Interventions and Neurodevelopmental Outcomes in School-Age Preterm Children and Adolescents: A Systematic Review
Authors: Ha-Vinh Leuchter Russia , Siffredi Vanessa
Published: October 2024

Objective:

To systematically review nonpharmaceutical interventions aiming to enhance neurodevelopment in preterm children and adolescents (aged 4–18 years).

Method:

A systematic review of the literature was conducted for all studies published up to May 1, 2022, across Medline, Web of Science, and PsycINFO databases. Studies were evaluated for inclusion by 2 independent reviewers using predetermined inclusion criteria. The Risk of Bias In Non-randomized Studies of Interventions and the Cochrane risk-of-bias tool for randomized trials (RoB 2) tools were used to assess bias in the selected studies.

Results:

Of the 1778 articles identified, 23 were included. Quality assessment revealed moderate bias in 52.2%, low bias in 21.7%, and serious bias in 26.1%. The selected studies comprised 60.9% randomized controlled trials and 21.7% pre- versus postdesigns. Interventions included Cogmed Working Memory Training® (43.5%), BrainGame Brian (13%), physiotherapy (13%), and others (30.4%). Qualitative analysis showed the limited impact of interventions on neurodevelopmental outcomes in preterm children aged 4–18 years.

Conclusion:

Despite recent efforts to use more rigorous methodologies, current research on school-age interventions for preterm neurodevelopment exhibits methodological limitations. There is a pressing need for well-designed, large-scale clinical trials to evaluate the efficacy of nonpharmaceutical interventions in this vulnerable population.
Maternal Mobile Device Use and Mealtime Interactions With Children
Authors: Radesky Jenny S. , Weeks Heidi M. , McCaffery Harlan , Kaciroti Niko , Lumeng Julie C. , Miller Alison L.
Published: October 2024

Objective:

This study examined (1) whether different types of mobile device use are associated with quantity/quality of parent–child interactions and (2) moment-to-moment changes in quantity/quality of parent–child interactions when devices are used.

Method:

In 47 videorecorded home mealtimes conducted in 2011 to 2013, we conducted detailed coding of maternal device use (talking, texting/scrolling, having device on table), frequency of mother and child verbalizations, child bids for attention, and maternal response to bids (contingent, no response, negative response) in 5-second intervals. We examined between-mother differences in parent–child interaction variables for a 10-percentage point increase in each type of device use comparisons using negative binomial or logistic regression. We then compared intervals when there was active mobile device use to nonuse intervals using generalized estimating equation logistic regression, predicting the odds of each parent–child interaction variable.

Results:

Mothers averaged 29.8 years (SD 6.10), child age 5.97 years (SD 0.56), and 55% had completed at least some college. Higher percentage of time spent texting/scrolling was associated with a lower rate of maternal verbalization (adjusted rate ratio 0.89 [95% confidence interval, 0.84–0.95]) and contingent response (adjusted rate ratio 0.92 [0.84–1.00]) and higher odds of nonresponse (adjusted odds ratio 1.13 [1.04–1.22]). In each 5-second interval of active device use, there was decreased odds of maternal verbalizations (adjusted odds ratio 0.48 [0.34–0.69]), child verbalizations (0.62 [0.44–0.88]), contingent response (0.45 [0.28–0.74]), and higher odds of maternal nonresponse (2.36 [1.40–4.00]).

Conclusion:

These results demonstrate decreased parent–child verbal interaction and lower parent responsiveness during mobile device use, particularly with texting and scrolling.
Drug treatments to prevent first decompensation in cirrhosis
Authors: Kezer Camille A. , Berzigotti Annalisa , Fortune Brett E. , Simonetto Douglas A.
Published: October 2024

Cirrhosis is a prevalent condition affecting more than 100 million people globally and carrying significant morbidity and mortality related to the development of portal hypertension and hepatic decompensation. Current treatment is primarily targeted at identifying chronic liver disease early and preventing the progression of fibrosis by treating the underlying etiology of liver disease. Treatment options for patients with advanced fibrosis are limited, and the only drug class approved for the prevention of hepatic decompensation remains nonselective beta-blockers. There are several pharmacological therapies being developed in both preclinical and clinical trials to explore their efficacy in preventing first hepatic decompensation. Most studies evaluate primary endpoints reflective of disease severity and portal hypertension, such as changes in HVPG or fibrosis stage based on histology or imaging. While many drugs are being investigated, much work is still needed to identify treatment targets with effective outcomes to move the needle in the field of cirrhosis management. This narrative review will address the current state of cirrhosis therapies, including potential new therapeutic targets, and provide direction on future advancements that will improve our current treatment paradigm and lead to better outcomes for those burdened with cirrhosis.
Toripalimab: a promising immunotherapeutic advancement in the management of nasopharyngeal carcinoma
Authors: Singh Ajeet , Riaz Rumaisa , Shaukat Ayesha , Ahsan Areeba , Kumar Aashish , Ojha Kartikeya , Akilimali Aymar
Published: October 2024

Nasopharyngeal carcinoma (NPC) poses a formidable challenge globally, particularly in regions with high Epstein-Barr virus (EBV) prevalence such as Southern China and Southeast Asia. This malignancy is primarily managed through radiotherapy, with recent advances incorporating induction chemotherapy and immunotherapy showing promise in improving treatment outcomes. Toripalimab, a programmed death receptor-1 (PD-1) blocking antibody, has emerged as a significant therapeutic option, demonstrating efficacy in both monotherapy and combination regimens in clinical trials such as POLARIS-02 and JUPITER-02. However, challenges including immune-related adverse events warrant careful consideration. This article focuses on toripalimab exploring its characteristics, dosage, mechanism of action, and potential benefits in the management of NPC. It aims to provide valuable insights into this treatment option, helping people better understand the potential benefits of toripalimab in managing this rare condition.
Ocular and Systemic Abnormalities in Punctal Agenesis
Authors: Marshall Rayna F. , Landau-Prat Daphna , Strong Alanna , Katowitz James A. , Katowitz William R.
Published: October 2024

Background:

Punctal agenesis (PA) is a rare congenital anomaly that can occur in isolation or as part of an underlying syndrome. The benefit of genetic assessment in individuals with PA and clinical features that should prompt molecular workup has not been systematically studied. The aim of this study was to identify ocular and extraocular features associated with PA and determine its association with an underlying syndrome.

Methods:

A retrospective medical records review of ocular and extraocular medical histories in all patients diagnosed with PA at the Children’s Hospital of Philadelphia between 2009 and 2023 was conducted.

Results:

Forty-four patients were included, ages 3.3 ± 3.3 years. Our cohort was 31 males (70%). Twenty patients had isolated PA (45.5%), while 24 patients (54.5%) had other associated ocular or extraocular abnormalities. The most common ocular comorbidities were refractive disorders (n = 8, 33%), ptosis (n = 8, 33%), strabismus (n = 7, 29%), other eyelid disorders (n = 9, 38%), and amblyopia (n = 6, 25%). Nineteen (43%) individuals had systemic disorders and 18 (41%) underwent genetic testing. An associated genetic diagnosis was found in 17 (39%) individuals. The most common associated syndrome was ectodermal dysplasia. Systemic disorders were more prevalent in individuals with syndromic PA (4, 20% isolated PA vs. 15, 63%, PA-plus, p = 0.005).

Conclusions:

The presence of additional ocular abnormalities was associated with an increased rate of systemic disorders (63%). In individuals with PA who also exhibit additional ocular disorders, systemic evaluation and genetic workup should be considered.
Probable IgG4-related Orbital Disease Masked by Exuberant Ocular Surface Pseudoepitheliomatous Hyperplasia
Authors: Doctor Sumer , Vempuluru Vijitha S. , Mishra Dilip K. , Kaliki Swathi
Published: October 2024

A 40-year-old woman presented with a mass in her OS for 2 years. Examination revealed a large conjunctival lesion on the nasal bulbar conjunctiva OS and a small upper tarsal conjunctival lesion in the OD. Biopsy OD revealed inflammatory granulation tissue, and OS revealed pseudoepitheliomatous hyperplasia with granulation tissue. The lesion responded well to steroids. She was lost to follow-up and returned with an enlarged lesion with orbital extension and corneal perforation. Orbital exenteration was performed. The entire conjunctiva showed extensive epithelial downgrowth and mononuclear round cell infiltrates, predominantly plasma cells admixed with neutrophils suggestive of aggressive pseudoepitheliomatous hyperplasia. Orbital tissue showed ill-defined granuloma formation with acute on chronic inflammation and plasma cells. The tissue IgG4/IgG ratio was 34%, suggestive of probable IgG4-related orbital disease. Based on this case, we conclude that IgG4-related orbital disease can rarely cause conjunctival and scleral inflammation with secondary pseudoepitheliomatous hyperplasia-like changes.
China ARCHES: A Phase 3 Trial of Enzalutamide vs Placebo in Metastatic Hormone-Sensitive Prostate Cancer
Authors: Chang Yuan , Li Yonghong , Zeng Gongqian , Guo Hongqian , Hu Zhiquan , Zhang Xiaoping , He Dalin , He Zhisong , Zhang Dahong , Kadeerbai Haishan , Liu Yuning , Zhou Fangjian , Ye Dingwei
Published: October 2024

Purpose:

This study evaluated the efficacy and safety of enzalutamide vs placebo, both combined with androgen deprivation therapy, in Chinese men with metastatic hormone-sensitive prostate cancer.

Materials and Methods:

Patients were randomized 2:1 to enzalutamide 160 mg/day or placebo, both in combination with androgen deprivation therapy. The primary trial end point was the time to prostate-specific antigen progression. Selected secondary end points included radiographic progression-free survival, time to castration resistance, time to initiation of new antineoplastic therapy, undetectable prostate-specific antigen (<0.2 ng/mL) rate among patients with detectable levels at baseline, and safety.

Results:

From September 11, 2019, to November 18, 2022, 180 patients were randomized to treatment (enzalutamide: n = 120; placebo: n = 60). Baseline characteristics were balanced between the treatment arms. Median treatment duration in the enzalutamide vs the placebo arm was 25.66 vs 15.11 months. After 63 prostate-specific antigen progression events (enzalutamide: n = 23; placebo: n = 40), enzalutamide significantly reduced the hazard for prostate-specific antigen progression by 87% (hazard ratio: 0.130; 95% confidence interval: 0.076, 0.222; P < .0001) vs placebo. Radiographic progression-free survival, time to castration resistance, and achievement of undetectable prostate-specific antigen levels were increased with enzalutamide vs placebo, while treatment-emergent adverse event rates were similar. Serious and grade 3 to 4 treatment-emergent adverse events occurred in 35.3% and 52.1%, respectively, of enzalutamide recipients vs 20.3% and 39.0%, respectively, of placebo recipients.

Conclusions:

In Chinese men with metastatic hormone-sensitive prostate cancer, enzalutamide significantly reduced the hazard for prostate-specific antigen progression vs placebo when combined with androgen deprivation therapy. The China ARCHES (NCT04076059) results were consistent with those of the global ARCHES study (NCT02677896).
Urologist-Administered MRI-Guided Transurethral Ultrasound Ablation of the Prostate Using a Mobile Treatment Center: A Case Series
Authors: Childs Alexandria , Donkor Emmanuel , Wootton Cole , Chopra Rajiv , Cookson Michael , Stratton Kelly
Published: October 2024

Introduction:

Transurethral ultrasound ablation (TULSA) relies on real-time MRI to precisely control the treatment of prostate cancer and avoid side effects. To overcome limited urologist access to MRI, we present a case series on the first use of a mobile TULSA treatment center.

Methods:

Clinical outcomes were retrospectively reviewed from our institutional database. A mobile MRI scanner was installed next to a surgical hospital, equipped with the ablation system and MRI-compatible anesthesia. Manufacturer testing confirmed that mobile TULSA continued to meet the requirements of fixed installations. Patients underwent preoperative assessment of candidacy for anesthesia and treatment in a mobile MRI setting. Positioning, anesthesia induction, and device placement were performed in the MRI scanner room. The intended ablation zone was delineated by the urologist using magnetic resonance images acquired with treatment devices in place. Ablation was controlled by the treatment software and monitored by the urologist using real-time MRI. A Foley catheter was placed for postoperative drainage; the patients awoke in the mobile MRI before transfer to postanesthesia care unit.

Results:

Six patients underwent TULSA in the mobile treatment unit, with no intraoperative complications. The median procedure time was 3.2 hours, with workflow improvements during equipment setup, patient positioning, and treatment planning. Contrast-enhanced images confirmed devascularization of the index lesion and successful nerve sparing. Six-month follow-up demonstrated promising PSA and MRI findings, and improvements in lower urinary tract symptoms.

Conclusions:

TULSA can be safely administered by urologists using a mobile MRI treatment center. Mobile MRI units could be used to expand patient access to TULSA.
Durability of Laser Endoureterotomy for the Treatment of Benign Ureteral Strictures: A Systematic Review and Meta-Analysis
Authors: Bhojani Naeem , Miller Larry E. , Bhattacharyya Samir , Emiliani Esteban , Krambeck Amy , Kamphuis Guido M. , Chew Ben H.
Published: October 2024

Purpose:

Laser endoureterotomy is a common minimally invasive treatment of ureteral strictures. However, data evaluating the durability of this technique are limited. This systematic review and meta-analysis assessed treatment success rates after laser endoureterotomy for managing benign ureteral strictures.

Materials and Methods:

A systematic literature search identified studies published from January 2000 to December 2023 reporting outcomes of laser endoureterotomy for benign ureteral strictures. Random-effects meta-analysis models calculated treatment success rates at 3 months, 6 months, and annually thereafter until estimates became unreliable (standard error > 10%).

Results:

Nine studies comprising 308 patients (310 strictures) met eligibility criteria. The methodological quality of the studies was rated as good in 8 studies and fair in 1 study. Strictures were most commonly attributable to stone disease or previous surgery, predominantly located in the proximal (38%) or distal (35%) ureter, with a median length of 10 mm. Holmium laser was used in 98% of cases. Intraoperative complication rates were low (0.9%). The treatment success rate was 84% at 3 months, 74% at 1 year, 70% at 2 years, and 68% at 3 years. Sensitivity analysis indicated that the results were not overly influenced by any single study, and modest heterogeneity was observed among studies.

Conclusions:

Minimally invasive laser endoureterotomy is an effective and durable treatment for short benign ureteral strictures, making it a viable alternative to reconstructive surgery.
Differences in Exposures to Adverse Childhood Experiences by Primary Source of Health Care, Behavioral Risk Factor Surveillance System 2019–2020
Authors: Yang Alina W. , Blosnich John R.
Published: October 2024

Objectives:

To estimate the prevalence of adverse childhood experiences (ACEs) among a population-based sample of adults in the United States by their primary source of health care.

Background:

Debate continues around the effectiveness and implementation of health care–based screening of ACEs. However, it is unclear how the burden of ACEs would be distributed across different sources of health care (ie, what a health system might expect should it implement ACEs screening).

Methods:

Data are from 8 U.S. states that include optional modules for ACEs and health care utilization in their 2019 or 2020 Behavioral Risk Factor Surveillance System survey. The analytic sample includes respondents with completed interviews (n = 45,820). ACEs were categorized into ordinal categories of 0, 1, 2, 3, or ≥4; and the prevalence of ACEs was summarized across 5 sources of health care: (1) employer-based or purchased plan; (2) Medicare, Medicaid, or other state programs; (3) TRICARE, Veterans Affairs, or military (ie, military-related health care); (4) Indian Health Service; or (5) some other source. All estimates were weighted to account for the complex sampling design.

Results:

Across all health insurance types, at least 60% of individuals reported at least one ACE. The greatest prevalence of patients reporting ≥4 ACEs occurred for military-related health care (21.6%, 95% CI = 18.2–25.5) and Indian Health Service (45.4%, 95% CI = 22.6–70.3).

Conclusions:

ACEs are extremely common across sources of health care, but some health systems have greater proportions of patients with high ACE exposures. The unique strengths and challenges of specific health care systems need to be integrated into the debate about clinical ACEs screening.
Platelet-derived extracellular vesicles in cardiovascular disease and treatment – from maintaining homeostasis to targeted drug delivery
Authors: Weiss Luisa , Macleod Hayley , Maguire Patricia B.
Published: October 2024

Purpose of review

Cardiovascular disease (CVD) remains a major global health burden. Rising incidences necessitate improved understanding of the pathophysiological processes underlying disease progression to foster the development of novel therapeutic strategies. Besides their well recognized role in CVD, platelet-derived extracellular vesicles (PEVs) mediate inter-organ cross talk and contribute to various inflammatory diseases.

Recent findings

PEVs are readily accessible diagnostic biomarkers that mirror pathophysiological disease progression but also may confer cardioprotective properties. Monitoring the effects of modulation of PEV signatures through pharmacotherapies has also provided novel insights into treatment efficacy. Furthermore, exploiting their inherent ability to infiltrate thrombi, atherosclerotic plaques and solid tumours, PEVs as well as platelet-membrane coated nanoparticles are emerging as novel effective and targeted treatment options for CVD and cancer.

Collectively, in-depth characterization of PEVs in various diseases ultimately enhances their use as diagnostic or prognostic biomarkers and potential therapeutic targets, making them clinically relevant candidates to positively impact patient outcomes.
Novel intravesical therapies and delivery systems for the management of bladder cancer
Authors: Grobet-Jeandin Elisabeth , Rouprêt Morgan , Seisen Thomas
Published: October 2024

Purpose of review

Bladder cancer is a substantial burden for public health worldwide. A risk-adapted treatment strategy is required for non muscle-invasive (NMIBC) and muscle-invasive bladder cancer (MIBC). To date, treatment includes surgery with or without peri-operative local or systemic treatment. The aim of this review was to explore novel intravesical therapies and delivery systems emerging in NMIBC and MIBC.

Recent findings

Several novel intravesical therapies and delivery systems for NMIBC and MIBC treatment recently emerged. Hyperthermic intravesical chemotherapy (HIVEC) allows a reasonable cancer control in selected high-risk NMIBC. Novel intravesical drugs such as nadofaragene firadenovec, Oncofid-P-B or Nogapendekin alfa-inbakicept seem to be safe and well tolerated. However, their efficacy in high-risk NMIBC should be further investigated. Hydrogels appear to be safe, well tolerated and potentially efficient in primary chemoablation in selected cases of low-grade intermediate-risk NMIBC tumors. Drug-releasing intravesical systems (drug-RIS) such as TAR-200 are safe and well tolerated, providing high partial and complete response rate in both NMIBC and MIBC patients.

The armamentarium for the treatment of bladder cancer patients is expanding, notably with HIVEC, hydrogels, drug-RIS and novel therapies. However, accurate patients’ selection is key to prevent disease progression in any bladder-sparing strategy, and radical cystectomy remains the gold-standard to date.
Adverse perinatal outcomes associated with different classes of antiretroviral drugs in pregnant women with HIV
Authors: Hey Molly , Thompson Lucy , Portwood Clara , Sexton Harriet , Kumarendran Mary , Brandon Zoe , Kirtley Shona , Hemelaar Joris
Published: October 2024

Objective:

Women with HIV (WHIV) are at an increased risk of adverse perinatal outcomes compared to women without HIV, despite antiretroviral therapy (ART). There is evidence that the risk of adverse perinatal outcomes may differ according to ART regimen. We aimed to assess the risk of adverse perinatal outcomes among WHIV receiving different classes of ART, compared to women without HIV.

Design:

A systematic review and meta-analysis

Methods:

We searched Medline, CINAHL, Global Health, and EMBASE for studies published between January 1, 1980, and July 14, 2023. We included studies which assessed the risk of 11 predefined adverse perinatal outcomes among WHIV receiving nonnucleoside reverse transcriptase inhibitor (NNRTI)-based ART, protease inhibitor based ART or integrase strand transfer inhibitor (INSTI)-based ART, compared to women without HIV. The perinatal outcomes assessed were preterm birth (PTB), very PTB (VPTB), spontaneous PTB (sPTB), low birthweight (LBW), very LBW (VLBW), term LBW, preterm LBW, small for gestational age (SGA), very SGA (VSGA), stillbirth and neonatal death (NND). Random effects meta-analyses examined the risk of each adverse outcome in WHIV receiving NNRTI-based, protease inhibitor based, or INSTI-based ART, compared with women without HIV. Subgroup and sensitivity analyses were conducted based on country income status, study quality, and timing of ART initiation. The protocol is registered with PROSPERO, CRD42021248987.

Results:

Of 108 720 identified citations, 22 cohort studies including 191 857 women were eligible for analysis. We found that WHIV receiving NNRTI-based ART (mainly efavirenz or nevirapine) are at an increased risk of PTB (risk ratio 1.40, 95% confidence interval 1.27–1.56), VPTB (1.94, 1.25–3.01), LBW (1.63, 1.30–2.04), SGA (1.53, 1.17–1.99), and VSGA (1.48, 1.16–1.87), compared with women without HIV. WHIV receiving protease inhibitor based ART (mainly lopinavir/ritonavir or unspecified) are at an increased risk of PTB (1.88, 1.55–2.28), VPTB (2.06, 1.01–4.18), sPTB (16.96, 1.01–284.08), LBW (2.90, 2.41–3.50), VLBW (4.35, 2.67–7.09), and VSGA (2.37, 1.84–3.05), compared with women without HIV. WHIV receiving INSTI-based ART (mainly dolutegravir) are at an increased risk of PTB (1.17, 1.06–1.30) and SGA (1.20, 1.08–1.33), compared with women without HIV.

Conclusion:

The risks of adverse perinatal outcomes are higher among WHIV receiving ART compared with women without HIV, irrespective of the class of ART drugs. This underlines the need to further optimize ART in pregnancy and improve perinatal outcomes of WHIV.
Optimizing Catheter Verification
Authors: Stroeder Jonas , Multusch Malte , Berkel Lennart , Hansen Lasse , Saalbach Axel , Schulz Heinrich , Heinrich Mattias P. , Elser Yannic , Barkhausen Jörg , Sieren Malte Maria
Published: October 2024

Purpose

Accurate detection of central venous catheter (CVC) misplacement is crucial for patient safety and effective treatment. Existing artificial intelligence (AI) often grapple with the limitations of label inaccuracies and output interpretations that lack clinician-friendly comprehensibility. This study aims to introduce an approach that employs segmentation of support material and anatomy to enhance the precision and comprehensibility of CVC misplacement detection.

Materials and Methods

The study utilized 2 datasets: the publicly accessible RANZCR CLiP dataset and a bespoke in-house dataset of 1006 annotated supine chest x-rays. Three deep learning models were trained: a classification network, a segmentation network, and a combination of both. These models were evaluated using receiver operating characteristic analysis, area under the curve, DICE similarity coefficient, and Hausdorff distance.

Results

The combined model demonstrated superior performance with an area under the curve of 0.99 for correctly positioned CVCs and 0.95 for misplacements. The model maintained high efficacy even with reduced training data from the local dataset. Sensitivity and specificity rates were high, and the model effectively managed the segmentation and classification tasks, even in images with multiple CVCs and other support materials.

Conclusions

This study illustrates the potential of AI-based models in accurately and reliably determining CVC placement in chest x-rays. The proposed method shows high accuracy and offers improved interpretability, important for clinical decision-making. The findings also highlight the importance of dataset quality and diversity in training AI models for medical image analysis.
DIABEZE: Diabetes self-management among the elderly in a Belgian home for the aged: a best practice implementation project
Authors: Corremans Marleen , Ohenewaa Comfort , Van Steenberghe Isaura , Bekkering Trudy , Jespers Hilke
Published: October 2024

Objectives:

The aim of this project was to improve the self-management of diabetes among elderly residents in a Belgian home for the aged.

Introduction:

Diabetes is a common chronic condition with significant comorbidity. Incidence is increasing, but a third of patients with diabetes are unaware that they have the disease. The treatment of diabetes requires a multifactorial approach. Treatment guidelines on diabetes recommend involving patients in monitoring their condition because supported self-management improves daily glycemic control.

Methods:

This evidence implementation project used the JBI Evidence Implementation Framework, which follows three phases. In the first phase, the area of change, stakeholders’ role, and practice context and readiness for change are investigated. In the second phase, a baseline audit is conducted to compare current practice with best practice. Strategies are then implemented to address any areas of non-compliance with best practice. In the third phase, a follow-up audit is conducted to evaluate changes in practice.

Results:

At baseline, six criteria had 0% compliance, two criteria had compliance lower than 50%, and only 49% of health care workers were familiar with the procedure for hypoglycemia treatment. Improvement strategies included creating awareness among health workers. In the follow-up audit, one criterion improved from 0% to 100%, three criteria improved from 0% to 85%, two criteria reached the threshold of 50% compliance, and one criterion reached 19%. Further audits are needed to ensure sustainability.

Conclusions:

This project improved diabetes self-management in elderly people living in a Belgian home for the aged. An in-depth planning phase with internal facilitation and interdisciplinary collaboration between all co-workers addressed barriers related to quality systems, structure, communication, and education.

Spanish abstract:

http://links.lww.com/IJEBH/A258
A burrowing annelid from the early Cambrian
Authors: Yang Xiaoyu , Aguado M. Teresa , Yang Jie , Bleidorn Christoph
Published: October 2024

Soft-bodied fossils of annelids from the Cambrian are relatively rare but provide vital insights into the early evolution and diversification of annelids. Here we describe a new annelid,
Xiaoshibachaeta biodiversa
gen. et sp. nov., from the early Cambrian (Stage 3) Xiaoshiba biota of Kunming, Yunnan Provence, China. This worm is obliquely oriented in the sediment, and is characteristic of a cephalic cage-like structure formed by the anteriorly directed parapodia and long chaetae of chaetiger 1, strongly suggesting an endobenthic lifestyle. This first report of an annelid worm from the Xiaoshiba biota provides the earliest known plausible evidence of burrowing behaviour in Annelida. Phylogenetic analyses recover
X. biodiversa
in the polytomy with other crown-group Annelida, indicating that the evolution of cephalic cage in Annelida is most likely convergent.
A model of task-level human stepping regulation yields semistable walking
Authors: Patil Navendu S. , Dingwell Jonathan B. , Cusumano Joseph P.
Published: October 2024

A simple lateral dynamic walker, with swing leg dynamics and three adjustable input parameters, is used to study how motor regulation affects frontal-plane stepping. Motivated by experimental observations and phenomenological models, we imposed task-level multi-objective regulation targeting the walker’s optimal lateral foot placement at each step. The regulator prioritizes achieving step width and lateral body position goals to varying degrees by choosing a mixture parameter. Our model thus integrates a lateral
mechanical template
, which captures the fundamental mechanics of frontal-plane walking, with a lateral
motor regulation template
, an empirically verified model of how humans manipulate lateral foot placements in a goal-directed manner. The model captures experimentally observed stepping fluctuation statistics and demonstrates how linear empirical models of stepping dynamics can emerge from first-principles nonlinear mechanics. We find that task-level regulation gives rise to a goal-equivalent manifold in the system’s extended state space of mechanical states and inputs, a subset of which contains a continuum of period-1 gaits forming a
semistable
set: perturbations off of any of its gaits result in transients that return to the set, though typically to different gaits.
Trade-offs and thermodynamics of energy-relay proofreading
Authors: Berx Jonas , Proesmans Karel
Published: October 2024

Biological processes that are able to discriminate between different molecules consume energy and dissipate heat, using a mechanism known as proofreading. In this work, we thoroughly analyse the thermodynamic properties of one of the most important proofreading mechanisms, namely Hopfield’s energy-relay proofreading. We discover several trade-off relations and scaling laws between several kinetic and thermodynamic observables. These trade-off relations are obtained both analytically and numerically through Pareto optimal fronts. We show that the scheme is able to operate in three distinct regimes: an energy-relay regime, a mixed relay-Michaelis–Menten (MM) regime and a Michaelis–Menten regime, depending on the kinetic and energetic parameters that tune transitions between states. The mixed regime features a dynamical phase transition in the error-entropy production Pareto trade-off, while the pure energy-relay regime contains a region where this type of proofreading energetically outperforms standard kinetic proofreading.
Spatial correlations in laboratory insect swarms
Authors: Reynolds Andy M.
Published: October 2024

In contrast with flocks of birds, schools of fish and herds of animals, swarms of the non-biting midge
Chironomus riparius
do not possess global order and under quiescent conditions velocities are only weakly correlated at long distances. Without such order it is challenging to characterize the collective behaviours of the swarms which until now have only been evident in their coordinated responses to disturbances. Here I show that the positions of the midges in laboratory swarms are maximally anticorrelated. This novel form of long-range ordering has until now gone unnoticed in the literature on collective animal movements. Here, its occurrence is attributed to midges being, in nearly equal measure, attracted towards the centre of the swarm and repelled by one another. It is shown that the midge swarms are poised at the cusp of a stable–unstable phase transition.
The influence of talus size and shape on
in vivo
talocrural hopping kinematics
Authors: Behling Anja-Verena , Kelly Luke , Welte Lauren , Rainbow Michael J.
Published: October 2024

Talus morphology (shape and size) plays a pivotal role in talocrural joint function. Despite its importance, the relationship between talus morphology, particularly the talar dome, and dynamic,
in vivo
talocrural function is poorly understood. Understanding these form–function relationships in a healthy cohort is essential for advancing patient-specific treatments aimed at restoring function. Nine participants (five females) hopped on one leg while biplanar videoradiography and ground reaction forces were simultaneously collected. Three-dimensional bone models were created from computed tomography scans. Helical axes of motion were calculated for the talus relative to the tibia (rotation axes), and a cylinder was fitted through the talar dome (morphological axis). Bland–Altman plots and spatial angles were used to examine the level of agreement between the rotation and morphological axes. A shape model of 36 (15 females) participants was established, and a cylinder fit was morphed through the range of ±3 standard deviations. The rotation and morphological axes largely agree regarding their orientation and location during hopping. The morphological axes were consistently oriented more anteriorly during landing than the rotation axes. Some shape components affect talar dome orientation and curvature independent of size. This suggests that besides bone size, the shape of the talar dome might influence the movement pattern during locomotion. Our findings may further inform talocrural joint arthroplasty design.
Personality testing of large language models: limited temporal stability, but highlighted prosociality
Authors: Bodroža Bojana , Dinić Bojana M. , Bojić Ljubiša
Published: October 2024

As large language models (LLMs) continue to gain popularity due to their human-like traits and the intimacy they offer to users, their societal impact inevitably expands. This leads to the rising necessity for comprehensive studies to fully understand LLMs and reveal their potential opportunities, drawbacks and overall societal impact. With that in mind, this research conducted an extensive investigation into seven LLMs, aiming to assess the temporal stability and inter-rater agreement on their responses on personality instruments in two time points. In addition, LLMs’ personality profile was analysed and compared with human normative data. The findings revealed varying levels of inter-rater agreement in the LLMs’ responses over a short time, with some LLMs showing higher agreement (e.g. Llama3 and GPT-4o) compared with others (e.g. GPT-4 and Gemini). Furthermore, agreement depended on used instruments as well as on domain or trait. This implies the variable robustness in LLMs’ ability to reliably simulate stable personality characteristics. In the case of scales which showed at least fair agreement, LLMs displayed mostly a socially desirable profile in both agentic and communal domains, as well as a prosocial personality profile reflected in higher agreeableness and conscientiousness and lower Machiavellianism. Exhibiting temporal stability and coherent responses on personality traits is crucial for AI systems due to their societal impact and AI safety concerns.
The effect of experimental warming on reproductive performance and parental care in the burying beetle
Nicrophorus nepalensis
Authors: Malik Tanzil Gaffar , Jarrett Benjamin J. M. , Sun Syuan-Jyun
Published: October 2024

Rising temperatures can adversely affect parental care and reproductive performance across a range of taxa. However, the warming impact is contingent upon understanding how temperature affects the spectrum of parental behaviours and their interplay. Here, we assessed how temperature affects parental care and reproductive success in the burying beetle,
Nicrophorus nepalensis
, which exhibits complex parental care behaviours. We exposed breeding pairs of
N. nepalensis
, to three temperature regimes (18°C, 20°C and 22°C) and assessed changes in parental care, and the subsequent development and growth of their offspring. Our findings show that 22°C disrupts carcass nest building by the parents and results in smaller clutches. Moreover, no eggs successfully hatched in the 22°C treatment. A milder increase to 20°C did not affect the hatching rate but resulted in smaller broods and lighter offspring, even when considering brood size, suggesting a change in post-hatching care quality. Our research suggests that warming may weakly affect parental care but has strong detrimental effects on offspring performance. These findings highlight the necessity of investigating the effect of ambient temperature across a diversity of traits and behaviours and across a range of life-history stages to fully assess species vulnerability in the face of future climate change.
Evolutionary palaeoecology of European rhinocerotids across the Oligocene–Miocene transition
Authors: Hullot Manon , Martin Céline , Blondel Cécile , Becker Damien , Rössner Gertrud E.
Published: October 2024

The Oligocene–Miocene transition witnessed great environmental and faunal changes, spanning from late Oligocene to early Miocene (MP28–MN3). Its drivers and consequences on mammals are, however, poorly understood. Rhinocerotoids are among the most affected taxa, reflected by great taxonomical and morphological changes. However, potential associated changes in ecology have not been explored. Here, we investigated the palaeoecology of 10 rhinocerotid species coming from 15 localities across Western Europe and ranging from MP28 to MN3. We explored evolutionary trends for diet, physiology and habitat via dental wear, hypoplasia, body mass and stable isotopy. All rhinocerotids studied were C3 feeders, whether browsing or mixed-feeding, but clear dietary differences were observed at some localities and between Oligocene and Miocene rhinocerotids. The prevalence of hypoplasia was low (less than 10%) to moderate (less than 20%), but there were great differences by loci, species and localities. Body mass covaried with hypoplasia prevalence, suggesting that larger species might be more susceptible to stresses and environmental changes. We reconstructed similar warm conditions at all localities except Gaimersheim, but found greater variations in precipitation. Indeed, a clear shift in δ
13
C values was noticed at the end of the Oligocene, consistent with climatic and vegetation changes reported at that time.