bluuebunny/crossref_metadata_2025 huggingface dataset:
Dual-chamber leadless pacemaker in complex adult congenital heart disease: a case report
Authors: Ngan Ho Ting Abe , Fabbricatore Davide , Regan William , Rosenthal Eric , Wong Tom
Published: September 2024

Background

Atrioventricular block is common with adult congenital heart disease and pacemaker implantation is challenging. Atrioventricular synchronous pacing is important for better haemodynamics. This case reports the implantation of a dual-chamber leadless pacemaker in a patient with univentricular heart physiology and contributes to the literature regarding the management option in complex adult congenital heart disease patients with conduction abnormalities.

Case summary

A 25-year-old male with double inlet left ventricular, transposition of great arteries, hypoplastic aortic arch receive multiple surgeries including the Glenn shunt at the age of 1. He presented with 2:1 and 3:1 heart block at the age of 13 with a transvenous dual-chamber pacemaker implanted by pacing the superior vena cava stump and puncturing the Glenn shunt for the ventricular lead. A decade later, lead malfunctioned and the patient progressed to complete heart block. A subcutaneous implantable cardioverter defibrillator was implanted when he was 23 for monomorphic ventricular tachycardia. Given the anticipated challenges with transvenous lead extraction and epicardial pacemaker implantation, we implanted the novel dual-chamber leadless pacemakers which resulted in satisfactory atrioventricular synchronous pacing performance immediately post-op and 2 weeks after the procedure.

Discussion

We present a case of a novel dual-chamber leadless pacemaker implantation to maintain atrioventricular synchrony in the patient with complete heart block and univentricular physiology. This case illustrates an additional pacing option in complex adult congenital heart to maintain atrioventricular synchrony.
Diet and risk of atrial fibrillation: a systematic review
Authors: Gawałko Monika , Middeldorp Melissa E , Saljic Arnela , Penders John , Jespersen Thomas , Albert Christine M , Marcus Gregory M , Wong Christopher X , Sanders Prashanthan , Linz Dominik
Published: September 2024

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia. Comprehensive modification of established AF risk factors combined with dietary interventions and breaking deleterious habits has been shown to reduce AF burden and recurrence. Numerous AF risk factors, such as diabetes, obesity or hypertension can be partially related to dietary and lifestyle choices. Therefore, dietary interventions may have potential as a therapeutic approach in AF. Based on available data, current guidelines recommend alcohol abstinence or reduction to decrease AF symptoms, burden, and progression, and do not indicate the need for caffeine abstention to prevent AF episodes (unless it is a trigger for AF symptoms). Uncertainty persists regarding harms or benefits of other dietary factors including chocolate, fish, salt, polyunsaturated and monounsaturated fatty acids, vitamins, and micronutrients. This article provides a systematic review of the association between AF and both dietary patterns and components. Additionally, it discusses potentially related mechanisms and introduces different strategies to assess patients’ nutrition patterns, including mobile health solutions and diet indices. Finally, it highlights the gaps in knowledge requiring future investigation.
Untangling the colonization history of the Australo-Pacific reed warblers, one of the world’s great island radiations
Authors: Kearns Anna M , Campana Michael G , Slikas Beth , Berry Lainie , Saitoh Takema , Graves Gary R , Cibois Alice , Fleischer Robert C
Published: September 2024

Island radiations, such as those of the Australo-Pacific, offer unique insight into diversification, extinction, and early speciation processes. Yet, their speciation and colonization histories are often obscured by conflicting genomic signals from incomplete lineage sorting (ILS) or hybridization. Here, we integrated mitogenomes and genome-wide SNPs to unravel the evolutionary history of one of the world’s most geographically widespread island radiations. The Australo-Pacific reed warblers (Acrocephalus luscinius complex) are a speciose lineage including five species that have become extinct since the 19th century and ten additional species of conservation concern. The radiation spans over 10,000 km across Australo-Papua, Micronesia and Polynesia, including the Mariana, Hawaii and Pitcairn Island archipelagos. Earlier mtDNA studies suggested a stepping-stone colonization process, resulting in archipelago-level secondary sympatry of divergent mtDNA lineages in the Mariana Islands and Marquesas. These studies hypothesized that morphologically similar species on neighboring islands arose from ecological convergence. Using DNA from historical museum specimens and modern genetic samples, we show that ILS and/or gene flow have shaped the radiation of Australo-Pacific reed warblers rather than secondary sympatry. The nuclear genome reconstructs a simpler biogeographic history than mtDNA, showing close relationships between species in the Mariana Islands and Marquesas despite their paraphyletic mtDNA lineages. Gene flow likely involved early and late colonizing waves of the radiation before the loss of ancestral dispersive ability. Our results highlight how collection genomics can elucidate evolutionary history and inform conservation efforts for threatened species.
A haplotype-resolved, chromosome-scale genome for Malus domestica Borkh. ‘WA 38’
Authors: Zhang Huiting , Ko Itsuhiro , Eaker Abigail , Haney Sabrina , Khuu Ninh , Ryan Kara , Appleby Aaron B , Hoffmann Brendan , Landis Henry , Pierro Kenneth A , Willsea Noah , Hargarten Heidi , Yocca Alan E , Harkess Alex , Honaas Loren , Ficklin Stephen
Published: September 2024

Genome sequencing for agriculturally important Rosaceous crops has made rapid progress both in completeness and annotation quality. Whole genome sequence and annotation give breeders, researchers, and growers information about cultivar-specific traits such as fruit quality and disease resistance, and inform strategies to enhance postharvest storage. Here we present a haplotype-phased, chromosomal-level genome of Malus domestica, ‘WA 38’, a new apple cultivar released to market in 2017 as Cosmic Crisp®. Using both short and long-read sequencing data with a k-mer-based approach, chromosomes originating from each parent were assembled and segregated. This is the first pome fruit genome fully phased into parental haplotypes in which chromosomes from each parent are identified and separated into their unique, respective haplomes. The two haplome assemblies, ‘Honeycrisp’ originated HapA and ‘Enterprise’ originated HapB, are about 650 Megabases each, and both have a BUSCO score of 98.7% complete. A total of 53,028 and 54,235 genes were annotated from HapA and HapB, respectively. Additionally, we provide genome-scale comparisons to ‘Gala’, ‘Honeycrisp’, and other relevant cultivars highlighting major differences in genome structure and gene family circumscription. This assembly and annotation was done in collaboration with the American Campus Tree Genomes project that includes ‘WA 38’ (Washington State University), ‘d’Anjou’ pear (Auburn University), and many more. To ensure transparency, reproducibility, and applicability for any genome project, our genome assembly and annotation workflow is recorded in detail and shared under a public GitLab repository. All software is containerized, offering a simple implementation of the workflow.
The Raf/LIN-45 C-terminal distal tail segment negatively regulates signaling in Caenorhabditis elegans
Authors: Townley Robert A , Stacy Kennedy S , Cheraghi Fatemeh , de la Cova Claire C
Published: September 2024

Raf protein kinases act as Ras-GTP sensing components of the ERK signal transduction pathway in animal cells, influencing cell proliferation, differentiation, and survival. In humans, somatic and germline mutations in the genes BRAF and RAF1 are associated with malignancies and developmental disorders. Recent studies shed light on the structure of activated Raf, a heterotetramer consisting of Raf and 14-3-3 dimers, and raised the possibility that a Raf C-terminal distal tail segment (DTS) regulates activation. We investigated the role of the DTS using the Caenorhabditis elegans Raf ortholog lin-45. Truncations removing the DTS strongly enhanced lin-45(S312A), a weak gain-of-function allele equivalent to RAF1 mutations found in patients with Noonan Syndrome. We genetically defined three elements of the LIN-45 DTS, which we termed the active site binding sequence (ASBS), the KTP motif, and the aromatic cluster. In the context of lin-45(S312A), the mutation of each of these elements enhanced activity. We used AlphaFold to predict DTS protein interactions for LIN-45, fly Raf, and human BRAF within the activated heterotetramer complex. We propose the following distinct functions for the LIN-45 DTS elements: (1) the ASBS binds the kinase active site as an inhibitor; (2) phosphorylation of the KTP motif modulates the DTS–kinase domain interaction; and (3) the aromatic cluster anchors the DTS in an inhibitory conformation. Human RASopathy-associated variants in BRAF affect residues of the DTS, consistent with these predictions. This work establishes that the Raf/LIN-45 DTS negatively regulates signaling in C. elegans and provides a model for its function in other Raf proteins.
Seeking Dental Healthcare in the Context of COVID-19 Pandemic: A Study Examining the Health Belief Model
Authors: Goldstein Aviv , Matalon Shlomo , Fridenberg Na’ama , Slutzky Hagay
Published: September 2024

Background and Objectives

The main purpose of the study was to examine the factors influencing older adults’ seeking dental care, in the context of coronavirus disease 2019 (COVID-19) pandemic, based on the Health Belief Model (HBM).

Research Design and Methods

Phone interviews were conducted using a structured questionnaire, among 200 older adults aged 65 and above, who are members of the Israeli largest sick fund Clalit Health Services, that were sampled through a systematic random sample. The data were collected between January 2022 and March 2022 and during September 2022.

Results

Our findings indicate that since the outbreak of COVID-19 in Israel, 61.5% and 55% of the participants reported visiting a dentist and a dental hygienist, respectively, and about a fifth of the participants have foregone care at both. Seeking dental care was associated with an increase in perceived threat, benefits, willingness to seek care, and with a decrease in perceived barriers. The HBM was found to be a suitable framework for illuminating older adults’ dental behavior, which explains 43% of the variance.

Discussion and Implications

The results of the study provided first-hand findings regarding seeking dental care during the COVID-19 pandemic. These findings emphasize the importance of providing dental services with clear recommendations about dental care and appropriate protective equipment, even under conditions of health concern, to enhance oral health services utilization.
The financial burden of noncommunicable diseases from out-of-pocket expenditure in sub-Saharan Africa: a scoping review
Authors: Odunyemi Adelakun , Islam Md Tauhidul , Alam Khurshid
Published: September 2024

The growing financial burden of noncommunicable diseases (NCDs) in sub-Saharan Africa (SSA) hinders the attainment of the sustainable development goals. However, there has been no updated synthesis of evidence in this regard. Therefore, our study summarizes the current evidence in the literature and identifies the gaps. We systematically search relevant databases (PubMed, Scopus, ProQuest) between 2015 and 2023, focusing on empirical studies on NCDs and their financial burden indicators, namely, catastrophic health expenditure (CHE), impoverishment, coping strategies, crowding-out effects and unmet needs for financial reasons (UNFRs) in SSA. We examined the distribution of the indicators, their magnitudes, methodological approaches and the depth of analysis. The 71 included studies mostly came from single-country (n = 64), facility-based (n = 52) research in low-income (n = 22), lower-middle-income (n = 47) and upper-middle-income (n = 10) countries in SSA. Approximately 50% of the countries lacked studies (n = 25), with 46% coming from West Africa. Cancer, cardiovascular disease (CVD) and diabetes were the most commonly studied NCDs, with cancer and CVD causing the most financial burden. The review revealed methodological deficiencies related to lack of depth, equity analysis and robustness. CHE was high (up to 95.2%) in lower-middle-income countries but low in low-income and upper-middle-income countries. UNFR was almost 100% in both low-income and lower-middle-income countries. The use of extreme coping strategies was most common in low-income countries. There are no studies on crowding-out effect and pandemic-related UNFR. This study underscores the importance of expanded research that refines the methodological estimation of the financial burden of NCDs in SSA for equity implications and policy recommendations.
Deployment of an Artificial Intelligence Histology Tool to Aid Qualitative Assessment of Histopathology Using the Nancy Histopathology Index in Ulcerative Colitis
Authors: Rubin David T , Kubassova Olga , Weber Christopher R , Adsul Shashi , Freire Marcelo , Biedermann Luc , Koelzer Viktor H , Bressler Brian , Xiong Wei , Niess Jan H , Matter Matthias S , Kopylov Uri , Barshack Iris , Mayer Chen , Magro Fernando , Carneiro Fatima , Maharshak Nitsan , Greenberg Ariel , Hart Simon , Dehmeshki Jamshid , Peyrin-Biroulet Laurent
Published: September 2024

Background

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by increased stool frequency, rectal bleeding, and urgency. To streamline the quantitative assessment of histopathology using the Nancy Index in UC patients, we developed a novel artificial intelligence (AI) tool based on deep learning and tested it in a proof-of-concept trial. In this study, we report the performance of a modified version of the AI tool.

Methods

Nine sites from 6 countries were included. Patients were aged ≥18 years and had UC. Slides were prepared with hematoxylin and eosin staining. A total of 791 images were divided into 2 groups: 630 for training the tool and 161 for testing vs expert histopathologist assessment. The refined AI histology tool utilized a 4-neural network structure to characterize images into a series of cell and tissue type combinations and locations, and then 1 classifier module assigned a Nancy Index score.

Results

In comparison with the proof-of-concept tool, each feature demonstrated an improvement in accuracy. Confusion matrix analysis demonstrated an 80% correlation between predicted and true labels for Nancy scores of 0 or 4; a 96% correlation for a true score of 0 being predicted as 0 or 1; and a 100% correlation for a true score of 2 being predicted as 2 or 3. The Nancy metric (which evaluated Nancy Index prediction) was 74.9% compared with 72.3% for the proof-of-concept model.

Conclusions

We have developed a modified AI histology tool in UC that correlates highly with histopathologists’ assessments and suggests promising potential for its clinical application.
Uncrewed surface vehicles (USVs) as platforms for fisheries and plankton acoustics
Authors: Handegard Nils Olav , De Robertis Alex , Holmin Arne Johannes , Johnsen Espen , Lawrence Joshua , Le Bouffant Naig , O'Driscoll Richard , Peddie David , Pedersen Geir , Priou Pierre , Rogge Rabea , Samuelsen Mikal , Demer David A
Published: September 2024

Uncrewed surface vehicles (USVs) equipped with echosounders have the potential to replace or enhance acoustic observations from conventional research vessels (RVs), increase spatial and temporal coverage, and reduce cost and carbon emission. We discuss the objectives, system requirements, infrastructure, and regulations for using USVs with echosounders to conduct ecological experiments, acoustic-trawl surveys, and long-term monitoring. We present four example applications of USVs with lengths <8 m, and highlight some advantages and disadvantages relative to RV-based data acquisitions. Sail-driven USVs operate continuously for months and are more mature than motorized USVs, but they are slower. To maintain the pace of an RV, multiple sail-powered USVs sample in coordination. In comparison, motorized USVs can travel as fast as RVs and therefore may facilitate a combined survey, interleaving USV and RV transects, with RV-based biological sampling. Important considerations for all USVs include platform design, noise and transducer motion mitigation, communications and operations infrastructure, onboard data processing, biological sampling approach, and legal requirements. This technology is evolving and applied in multiple disciplines, but further development and institutional commitment are needed to allow USVs equipped with echosounders to become ubiquitous and useful components of a worldwide network of autonomous ocean observation platforms.
Calibration and comparison of SIR, SEIR/SLIR and SLAIR models for influenza dynamics: insights from the 2016-2017 season in the Valencian Community, Spain
Authors: Adenane Rim , Andreu-Vilarroig Carlos , Avram Florin , Villanueva Rafael-Jacinto
Published: September 2024

Influenza and influenza-like illnesses pose significant challenges to healthcare systems globally. Mathematical models play a crucial role in understanding their dynamics, calibrating them to specific scenarios and making projections about their evolution over time. This study proposes a calibration process for three different but well-known compartmental models—SIR, SEIR/SLIR and SLAIR—using influenza data from the 2016–2017 season in the Valencian Community, Spain. The calibration process involves indirect calibration for the SIR and SLIR models, requiring post-processing to compare model output with data, while the SLAIR model is directly calibrated through direct comparison. Our calibration results demonstrate remarkable consistency between the SIR and SLIR models, with slight variations observed in the SLAIR model due to its unique design and calibration strategy. Importantly, all models align with existing evidence and intuitions found in the medical literature. Our findings suggest that at the onset of the epidemiological season, a significant proportion of the population (ranging from 29.08% to 43.75% of the total population) may have already entered the recovered state, likely due to immunization from the previous season. Additionally, we estimate that the percentage of infected individuals seeking healthcare services ranges from 5.7% to 12.2%. Through a well-founded and calibrated modeling approach, our study contributes to supporting, settling and quantifying current medical issues despite the inherent uncertainties involved in influenza dynamics. The full Mathematica code can be downloaded from https://munqu.webs.upv.es/software.html.
Oscillations in a tumor–immune system interaction model with immune response delay
Authors: Huo Zhaoxuan , Huang Jicai , Kuang Yang , Ruan Shigui , Zhang Yuyue
Published: September 2024

In this paper we consider a tumor–immune system interaction model with immune response delay, in which a nonmonotonic function is used to describe immune response to the tumor burden and a time delay is used to represent the time for the immune system to respond and take effect. It is shown that the model may have one, two or three tumor equilibria, respectively, under different conditions. Time delay can only affect the stability of the low tumor equilibrium, and local Hopf bifurcation occurs when the time delay passes through a critical value. The direction and stability of the bifurcating periodic solutions are also determined. Moreover, the global existence of periodic solutions is established by using a global Hopf bifurcation theorem. We also observe the existence of relaxation oscillations and complex oscillating patterns driven by the time delay. Numerical simulations are presented to illustrate the theoretical results.
Neisseria gonorrhoeae treatment failure to the recommended antibiotic regimen—Québec, Canada, 2015–19
Authors: Blouin Karine , Lefebvre Brigitte , Trudelle Annick , Defay Fannie , Perrault-Sullivan Gentiane , Gnimatin Jean-Pierre , Labbé Annie-Claude
Published: September 2024

Objective

To describe Neisseria gonorrhoeae treatment failure to the recommended antimicrobial regimens (azithromycin, cefixime and ceftriaxone).

Methods

Our study was a longitudinal analysis of treatment failures from an observational open cohort of gonococcal infection cases collected in Québec, Canada (n = 2547) between September 2015 and December 2019. Epidemiological and clinical data were collected using a self-administered questionnaire, direct case interviews and chart reviews. Antimicrobial susceptibility testing was performed using the agar dilution method. To be retained as a treatment failure, cases must have had (i) a laboratory-confirmed gonococcal infection; (ii) a documented treatment; (iii) a positive test of cure (TOC) performed within a defined period and (iv) no sexual contact (vaginal, oral or anal), even protected with a condom, between the beginning of treatment and the positive TOC. A broader definition, including suspected cases, was also examined.

Results

Among 1593 cases where a TOC was performed, 83 had a positive TOC: 11 were retained as treatment failure, and 6 were considered suspected cases (overall = 17/1593; 1.1%). Possible explanations for retained or suspected treatment failure included resistance to the antibiotics used for treatment (n = 1), pharyngeal infection (n = 9, of which 5 had been treated with ceftriaxone and 4 with other regimens); and azithromycin monotherapy (n = 1). Some cases had more than one potential explanation.

Conclusions

Treatment failure occurred in 1.1% of cases of Neisseria gonorrhoeae infection for which a TOC was performed, including some cases of pharyngeal infection treated with ceftriaxone.
Lodestar DX, an evaluation: loop-mediated isothermal amplification (LAMP) for the diagnosis of urinary tract infection in symptomatic adult females
Authors: Diggle Joanna , Van Der Goes Van Naters Ayako , Roula Mohammed Ali , Mitchell Shanine , Whiffen Dewi , Nieuwland Jeroen , Hayhurst Emma
Published: September 2024

Background

Over 404.6 million people are affected worldwide each year by urinary tract infections (UTIs), with ∼237 000 associated deaths globally in 2019. Much more common in women than men, acute UTI occurs in up to 50% of the female population. Despite this, there is a lack of good diagnostic tools for use at the point-of-care, and over- and under-diagnosis are common, leading to long-term complications and patient suffering, and driving the spread of antimicrobial resistance through insufficient appropriate antibiotic stewardship.

Objectives

To evaluate the performance of a novel point-of-care testing platform, Lodestar DX, in comparison with standard laboratory processing of urine specimens.

Methods

A total of 199 fresh urine samples from symptomatic adult females suspected of having an acute UTI were tested using Lodestar DX and the results compared with standard laboratory methods performed at a local microbiology laboratory.

Results

Using standard laboratory methods, 129/199 samples produced a result and could be compared. Overall sensitivity and specificity of Lodestar DX were 88.1% (95% CI: 77.8%–94.7%) and 83.9% (95% CI: 72.3%–92.0%), respectively (n = 129), with a positive predictive value of 85.5% (95% CI: 76.9%–91.3%), a negative predictive value of 86.7% (95% CI: 77.1%–92.6%) and an overall accuracy of 86.1% (95% CI: 78.9%–91.5%).

Conclusions

The results show good correlation between Lodestar DX results and those of the standard laboratory method for this patient group. However, the platform would benefit from further testing to establish its true point-of-care compatibility and a direct comparison between this and other testing methods, such as urine dipstick testing.
The dynamic roles of intracellular vacuoles in heavy metal detoxification by Rhodotorula mucilaginosa
Authors: Shi Yixiao , Tang Lingyi , Shao Qi , Jiang Yizhou , Wang Zhijun , Peng Chao , Gu Tingting , Li Zhen
Published: September 2024

Aims

Rhodotorula mucilaginosa (Rho) can develop a range of strategies to resist the toxicity of heavy metals. This study aimed to investigate the physiological responses and transcriptomic regulation of the fungus under different heavy metal stresses.

Methods and results

This study applied transmission electron microscopy and RNA-seq to investigate the fungal resistance to Pb, Cd, and Cu stresses. Under Pb stress, the activated autophagy-related genes, vesicle-fusing ATPase, and vacuolar ATP synthase improved vacuolar sequestration. This offsets the loss of lipids. However, the metal sequestration by vacuoles was not improved under Cd stress. Vacuolar fusion was also inhibited following the interference of intravacuolar Ca2+ due to their similar ionic radii. Cu2+ showed the maximum toxic effects due to its lowest cellular sorption (as low as 7%) with respect to Pb2+ and Cd2+, although the efflux pumps and divalent metal ion transporters partially contributed to the detoxification.

Conclusions

Divalent cation transporters and vacuolar sequestration are the critical strategies for Rho to resist Pb stress. Superoxide dismutase (SOD) is the main strategy for Cd resistance in Rho. The intracellular Cu level was decreased by efflux pump and divalent metal ion transporters.
Exploring the impacts of fescue toxicosis on the pulmonary arterial pressure of angus cows
Authors: Rajo-Gomez E Benjamin , Giurgis Mariam , Pickworth Carrie L , Weaver Andrew R , Foster Derek M , Khanal Piush , Poole Daniel H
Published: September 2024

Vasoconstriction of peripheral blood vessels is one of the hallmark symptoms of fescue toxicosis in cattle. Thus, it was hypothesized that exposure to ergot alkaloids would increase the pulmonary arterial pressure (PAP). The objectives of this study were to examine the relationship between PAP and different physiological parameters of cows grazing either endophyte-infected (EI) or novel-endophyte (EN) fescue, then evaluate changes in PAP and other physiological measurements in cows exposed to EI pastures and deemed as susceptible or tolerant based on animal performance. Pregnant Angus cows at 2 different locations grazed either EI or EN fescue pastures for 14 consecutive weeks starting in early April of 2022. Forage measurements were collected to assess ergot alkaloid exposure throughout the study. In addition to measuring PAP, weekly measurements and blood samples were collected to evaluate physiological responses to ergot alkaloid consumption. The Fescue Toxicosis Selection Method (FTSM) was used for a post hoc analysis to identify cattle as either tolerant (EI-TOL) or susceptible (EI-SUS) when challenged with ergot alkaloid exposure. Data were analyzed using a MIXED procedure of SAS with repeated measures. Cows grazing on EN pastures had greater mean PAP values than EI cows, (P < 0.01), whereas a location effect was identified when comparing both EI-TOL and EI-SUS groups (P < 0.01). Cows exposed to EN pastures had greater average daily gain (ADG) (P = 0.04) and progesterone (P4) concentrations (P < 0.01), and lower hair shedding scores (HSS; P < 0.01) than EI cows. The EI-TOL cows tended to have greater final body weight, ADG and had lower HSS (P < 0.01) than EI-SUS cows. While cattle consuming EI tall fescue exhibited classical physiological changes, the decrease in PAP of cattle consuming EI fescue was unexpected and contradicted the initial hypothesis. Furthermore, the FTSM provides a means to identify animals with superior performance in spite of the chronic exposure to ergot alkaloids. Continued investigations examining the interaction between ergot alkaloid exposure and cardiovascular parameters will lead to a fuller understanding of the disease and are pivotal for developing innovative strategies that enhance best management practices to help guarantee the sustainability of the U.S. beef industry.
Benefits and harms of hepatocellular carcinoma screening outreach in patients with cirrhosis: a multicenter randomized clinical trial
Authors: Singal Amit G , Daher Darine , Narasimman Manasa , Yekkaluri Sruthi , Liu Yan , Cerda Vanessa , Banala Chaitra , Khan Aisha , Lee MinJae , Seif El Dahan Karim , Murphy Caitlin C , Kramer Jennifer R , Hernaez Ruben
Published: September 2024

Background

The value of hepatocellular carcinoma screening is defined by the balance of benefits from early tumor detection vs harms because of false-positive results. We evaluated the value of a mailed outreach strategy for hepatocellular carcinoma screening in patients with cirrhosis.

Methods

We conducted a multicenter pragmatic randomized clinical trial comparing mailed outreach for hepatocellular carcinoma screening (n = 1436) and usual care with visit-based screening (n = 1436) among patients with cirrhosis at 3 health systems from March 2018 to September 2021. Outcomes of interest were early stage hepatocellular carcinoma detection (ie, screening benefit) and diagnostic evaluation for false-positive or indeterminate results (ie, screening harm). Screening harm was categorized as mild, moderate, and severe based on number and type of diagnostic exams. All patients were included in intention-to-screen analyses.

Results

Of 125 patients diagnosed with hepatocellular carcinoma (67 outreach and 58 usual care), 71.2% were found at an early stage per the Milan criteria. Early tumor detection did not statistically significantly differ between the outreach and usual care arms (64.2% vs 79.3%; P = .06). The proportion of patients with physical harms also did not differ between the outreach and usual care arms (10.8% vs 10.7%; P = .95) with 5.9% in both arms having mild harms; 4.0% and 3.8%, respectively, with moderate harms; and 0.9% and 1.0%, respectively, with severe harms.

Conclusion

Most patients enrolled in hepatocellular carcinoma screening were detected at an early stage, and a minority experienced physical harms. A mailed outreach strategy did not increase early hepatocellular carcinoma detection or physical harms compared with usual care.

Clinical trials number

NCT02582918 and NCT03756051.
Spatial pattern and ecological adaptation of heterostylous and homostylous species of Primula in China
Authors: Li Shunqiu , Lyu Lisha , Lyu Tong , Dimitrov Dimitar , Wang Yunyun
Published: September 2024

Floral syndrome is one of the key components of plant pollination syndromes, affecting variety of evolutionary and ecological processes in angiosperms. The evolutionary transition from self-incompatible heterostyly to self-compatible homostyly occurred repeatedly in angiosperm families. Although the evolution of heterostyly and homostyly has been deeply studied, our understanding on their differences in ecological strategies is still lacking. In this work, using the floral syndrome and distributions of the Primula in China we compared the spatial pattern of floral syndrome frequency and its climatic determinants. Our results reveal that distylous and homostylous Primula have similar primary centers of species diversity in southwest China, while distylous species have larger range size than homostylous ones. Temperature seasonality is the dominant climate factor of these geographic patterns, but its effect is much stronger in distylous than in homostylous Primula. Distylous species have larger flower size and number, and fruit size than homostylous ones. Climate, especially temperature seasonality mainly influenced species range size via its effects on floral syndrome. Our study suggests that homostyly is likely derived from heterostylous ancestors in similar geographical context, and larger reproductive investment in floral phenotype may provide compensatory mechanisms for obligate out-breeding heterostyly. Future investigations regarding the evolutionary history and tolerance or resistance to environmental change between distyly and homostyly may greatly advance our understanding of their spatial pattern and adaptative differences.
The association between initiation weekday of radiotherapy and local control in stage 1 glottic carcinoma: a retrospective analysis
Authors: Endo Masashi , Takahashi Satoru , Fukuda Yukiko , Okada Kohei , Ogawa Kazunari , Nakamura Michiko , Kawahara Masahiro , Akahane Keiko , Murakami Eri , Shibayama Chiaki , Onaga Ryutaro , Nagatomo Takafumi , Kanazawa Takeharu , Nishino Hiroshi , Mori Harushi , Shirai Katsuyuki
Published: September 2024

Radiotherapy is one of the definitive treatments for head and neck squamous cell carcinoma, especially early-stage glottic squamous cell carcinoma. Although there are several studies on the initiation weekday of cancer treatment, there are very few studies in the radiotherapy field. Thus, the present study investigated whether the initiation weekday of radiotherapy affects the local control rate for stage 1 glottic squamous cell carcinoma. A total of 105 patients with stage 1 glottic squamous cell carcinoma underwent definitive radiotherapy alone between 2007 and 2021. The group in which radiotherapy was started between Monday and Wednesday was compared with the group in which radiotherapy was started on Thursday or Friday. Sixty-seven patients started radiotherapy between Monday and Wednesday and 38 on Thursday or Friday. The 5-year local control rate was 98% (95% confidence interval: 94–100%) in the Monday–Wednesday group and 83% (95% confidence interval: 71–96%) in the Thursday–Friday group, with a significant difference (P = 0.005). On multivariate analysis including age, overall administration time (days), fractionation, irradiation field size and initiation weekday of radiotherapy, no factors other than initiation weekday affecting local control were identified. Radiotherapy toxicity did not differ between the two groups. For stage 1 glottic squamous cell carcinoma, starting radiotherapy on Thursday or Friday is associated with a lower local control rate; therefore, radiotherapy should be started by Wednesday.
Optimal risk-assessment scheduling for primary prevention of cardiovascular disease
Authors: Gasperoni Francesca , Jackson Christopher H , Wood Angela M , Sweeting Michael J , Newcombe Paul J , Stevens David , Barrett Jessica K
Published: September 2024

In this work, we introduce a personalized and age-specific net benefit function, composed of benefits and costs, to recommend optimal timing of risk assessments for cardiovascular disease (CVD) prevention. We extend the 2-stage landmarking model to estimate patient-specific CVD risk profiles, adjusting for time-varying covariates. We apply our model to data from the Clinical Practice Research Datalink, comprising primary care electronic health records from the UK. We find that people at lower risk could be recommended an optimal risk-assessment interval of 5 years or more. Time-varying risk factors are required to discriminate between more frequent schedules for high-risk people.
Gallstone ileus: report of two cases and a mini literature review
Authors: Gerasopoulos Georgios , Karagianni Foteini , Nikas Spyridon , Besikiaris Dimitrios , Veniadou Kalliopi , Chondri Maria , Routis Panagiotis , Zonitsa Sotiria , Sgouridi Despoina , Karaklas Aggelos
Published: September 2024

Gallstone ileus is a relatively rare complication of cholelithiasis, and an uncommon cause of small bowel obstruction most commonly seen in elderly and debilitated people with associated comorbidities. Symptoms of gallstone ileus are insidious and may be vague while the delay in diagnosis results in a high mortality rate. Herein we report two cases of gallstone ileus in elderly patients with complex medical history who presented at the emergency department with abdominal pain and distension, vomiting and fluid/electrolyte disorders due to cholecysto-enteric fistula and bowel obstruction.
Relativistic SZ temperatures and hydrostatic mass bias for massive clusters in the FLAMINGO simulations
Authors: Kay Scott T , Braspenning Joey , Chluba Jens , Helly John C , Kugel Roi , Schaller Matthieu , Schaye Joop
Published: September 2024

The relativistic Sunyaev-Zel’dovich (SZ) effect can be used to measure intracluster gas temperatures independently of X-ray spectroscopy. Here, we use the large-volume FLAMINGO simulation suite to determine whether SZ y-weighted temperatures lead to more accurate hydrostatic mass estimates in massive ($M_{\rm 500c} \gt 7.5\times 10^{14}\, {\rm M}_{\odot }$) clusters than when using X-ray spectroscopic-like temperatures. We find this to be the case, on average. The median bias in the SZ mass at redshift zero is $\left\langle b \right\rangle \equiv 1-\left\langle M_{\rm 500c,hse}/M_{\rm 500c,true} \right\rangle = -0.05 \pm 0.01$, over 4 times smaller in magnitude than the X-ray spectroscopic-like case, $\left\langle b \right\rangle = 0.22 \pm 0.01$. However, the scatter in the SZ bias, $\sigma _{b} \approx 0.2$, is around 40 per cent larger than for the X-ray case. We show that this difference is strongly affected by clusters with large pressure fluctuations, as expected from shocks in ongoing mergers. Selecting the clusters with the best-fitting generalized NFW pressure profiles, the median SZ bias almost vanishes, $\left\langle b \right\rangle = -0.009 \pm 0.005$, and the scatter is halved to $\sigma _{b} \approx 0.1$. We study the origin of the SZ/X-ray difference and find that, at $R_{\rm 500c}$ and in the outskirts, SZ weighted gas better reflects the hot, hydrostatic atmosphere than the X-ray weighted gas. The SZ/X-ray temperature ratio increases with radius, a result we find to be insensitive to variations in baryonic physics, cosmology, and numerical resolution.
HaploSweep: Detecting and Distinguishing Recent Soft and Hard Selective Sweeps through Haplotype Structure
Authors: Zhao Shilei , Chi Lianjiang , Fu Mincong , Chen Hua
Published: September 2024

Identifying soft selective sweeps using genomic data is a challenging yet crucial task in population genetics. In this study, we present HaploSweep, a novel method for detecting and categorizing soft and hard selective sweeps based on haplotype structure. Through simulations spanning a broad range of selection intensities, softness levels, and demographic histories, we demonstrate that HaploSweep outperforms iHS, nSL, and H12 in detecting soft sweeps. HaploSweep achieves high classification accuracy—0.9247 for CHB, 0.9484 for CEU, and 0.9829 YRI—when applied to simulations in line with the human Out-of-Africa demographic model. We also observe that the classification accuracy remains consistently robust across different demographic models. Additionally, we introduce a refined method to accurately distinguish soft shoulders adjacent to hard sweeps from soft sweeps. Application of HaploSweep to genomic data of CHB, CEU, and YRI populations from the 1000 genomes project has led to the discovery of several new genes that bear strong evidence of population-specific soft sweeps (HRNR, AMBRA1, CBFA2T2, DYNC2H1, and RANBP2 etc.), with prevalent associations to immune functions and metabolic processes. The validated performance of HaploSweep, demonstrated through both simulated and real data, underscores its potential as a valuable tool for detecting and comprehending the role of soft sweeps in adaptive evolution.
Transcription start site scanning requires the fungi-specific hydrophobic loop of Tfb3
Authors: Yang Chun , Basnet Pratik , Sharmin Samah , Shen Hui , Kaplan Craig D , Murakami Kenji
Published: September 2024

RNA polymerase II (pol II) initiates transcription from transcription start sites (TSSs) located ∼30–35 bp downstream of the TATA box in metazoans, whereas in the yeast Saccharomyces cerevisiae, pol II scans further downstream TSSs located ∼40–120 bp downstream of the TATA box. Previously, we found that removal of the kinase module TFIIK (Kin28–Ccl1–Tfb3) from TFIIH shifts the TSS in a yeast in vitro system upstream to the location observed in metazoans and that addition of recombinant Tfb3 back to TFIIH-ΔTFIIK restores the downstream TSS usage. Here, we report that this biochemical activity of yeast TFIIK in TSS scanning is attributable to the Tfb3 RING domain at the interface with pol II in the pre-initiation complex (PIC): especially, swapping Tfb3 Pro51—a residue conserved among all fungi—with Ala or Ser as in MAT1, the metazoan homolog of Tfb3, confers an upstream TSS shift in vitro in a similar manner to the removal of TFIIK. Yeast genetic analysis suggests that both Pro51 and Arg64 of Tfb3 are required to maintain the stability of the Tfb3–pol II interface in the PIC. Cryo-electron microscopy analysis of a yeast PIC lacking TFIIK reveals considerable variability in the orientation of TFIIH, which impairs TSS scanning after promoter opening.
Comparative effectiveness of netupitant-palonosetron plus dexamethasone versus aprepitant-based regimens in mitigating chemotherapy-induced nausea and vomiting: a meta-analysis of randomized controlled trials
Authors: Luo Wun-Ting , Chang Chia-Lun , Huang Tsai-Wei , Gautama Made Satya Nugraha
Published: September 2024

Background

Despite guidelines for managing chemotherapy-induced nausea and vomiting (CINV), there remains a need to clarify the optimal use of neurokinin-1 (NK1) receptor antagonists. Comparing the effectiveness of NEPA (netupitant-palonosetron) plus dexamethasone with other NK1 antagonist-based regimens combined with a 5HT3 receptor antagonist and dexamethasone is crucial for informed decision-making and improving patient outcomes.

Methods

We conducted a systematic review of the literature to assess randomized controlled trials (RCTs) comparing the efficacy, safety, and cost-effectiveness of NEPA plus dexamethasone and other NK1 antagonist-based regimens combined with a 5HT3 receptor antagonist and dexamethasone. PubMed, Embase, and the Cochrane Library databases were systematically searched, with the latest update performed in December 2023. Data on patient demographics, chemotherapy regimen characteristics, and outcomes were extracted for meta-analysis using a random-effects model.

Results

Seven RCTs were analyzed. NEPA plus dexamethasone showed superior efficacy in achieving complete response in the overall (risk ratio [RR], 1.15; 95% CI, 1.02--1.30) and delayed phases (RR, 1.20; 95% CI, 1.03-1.41) of chemotherapy. It was more effective in controlling nausea (overall phase RR, 1.20; 95% CI, 1.05-1.36; delayed phase RR, 1.21; 95% CI, 1.05-1.40) and reducing rescue therapy use (overall phase RR, 1.45; 95% CI, 1.07-1.95; delayed phase RR, 1.75; 95% CI, 1.10-2.78). Adverse event rates were comparable (RR, 1.03; 95% CI, 0.96-1.10). Subgroup analysis indicated NEPA’s particular efficacy in patients receiving moderately emetogenic chemotherapy (RR, 1.31; 95% CI, 1.07-1.60).

Conclusion

NEPA plus dexamethasone regimens exhibit superior efficacy in preventing CINV, supporting their preferential inclusion in prophylactic treatment protocols. Its effective symptom control, safety profile, and cost-effectiveness endorse NEPA-based regimens as a beneficial option in CINV management.
Feasibility and tolerability of anlotinib plus PD-1 blockades as rechallenge immunotherapy in previously treated advanced ESCC: a retrospective study
Authors: Hong Yonggui , Liu Jun , Lu Ping , Chang Zhiwei , Zhang Guifang , Ma Xiumei , Liang Wei , Tian Yongjing , Xia Jin , Cao Heng , Huang Jing
Published: September 2024

Background

Rechallenge with immune checkpoint inhibitor (ICI) seemed favorable in several tumors, but clinical experience on esophageal squamous cell carcinoma (ESCC) was scanty. This real-world study aimed to assess the feasibility and safety of anlotinib plus ICI for patients with previously ICI-treated advanced ESCC.

Materials and Methods

We retrospectively identified advanced ESCC patients who received anlotinib plus ICI in the rechallenge setting for evaluation of clinical outcomes and safety. Totally 110 ICI-pretreated patients, of which 89 (80.9%) received prior first- or second-line treatment, were included from September 9, 2019, to November 30, 2022. Most patients (63.6%) discontinued initial ICI due to disease progression.

Results

After rechallenge, median overall survival (OS) and progression-free survival (PFS) were 11.1 (95% CI, 8.6-13.7) and 5.6 (95% CI, 4.4-6.8) months, respectively; estimated OS and PFS rates at 12 months were 47.6% (95% CI, 36.8%-57.7%) and 21.4% (95% CI, 10.9%-34.2%), respectively. No complete response was reported and 21 (19.1%) patients attained partial response; the objective response rate was 19.1%. Fifty-five (50.0%) had stable disease for a disease control rate of 69.1%. Of the 21 responders, median duration of response was 6.4 months. Tendencies for longer OS were observed in patients with Eastern Cooperative Oncology Group Performance of 0 (P = .056). The incidence of grade 3 or higher treatment-related adverse events was 10.0%.

Conclusion

Anlotinib plus ICI in the rechallenge setting was promising and resulted in encouraging benefits for patients with previously ICI-treated advanced ESCC. Our findings provided preliminary but unique evidence to help select ESCC patients benefiting from this strategy.

Trial registration

chictr.org.cn; number ChiCTR2300070777
Selective insensitivity to income held by the richest
Authors: Szaszi Barnabas , Habibnia Hooman , Tan Josephine , Hauser Oliver P , Jachimowicz Jon M
Published: September 2024

The misperception of income inequality is often touted as a critical barrier to more widespread support of redistributive policies. Here, we examine to what extent and why (mis)perceptions vary systematically across the income distribution. Drawing on data from four studies (N = 2,744)—including a representative sample and preregistered incentive-compatible experiments—we offer converging evidence that people specifically underestimate the amount of income held by the top of the income distribution. While this selective underestimation is likely driven by multiple mechanisms, including systemic factors, we find that cognitive biases contribute to the observed pattern of results. The rise of inequality in many developed countries has been documented before, and the fact that this growing inequality is largely driven by the outsized gains of the richest individuals may pose new challenges previously underappreciated: our theory and findings highlight that cognitive biases pose a key obstacle to people's recognition of the concentration of income among the richest individuals, and may potentially distort their preferences for redistribution. We conclude by discussing future directions for research and the importance of incorporating behavioral and cognitive limitations into the design of redistributive public policy.
Leveraging body-worn camera footage to assess the effects of training on officer communication during traffic stops
Authors: Camp Nicholas P , Voigt Rob , Hamedani MarYam G , Jurafsky Dan , Eberhardt Jennifer L
Published: September 2024

Can training police officers on how to best interact with the public actually improve their interactions with community members? This has been a challenging question to answer. Interpersonal aspects of policing are consequential but largely invisible in administrative records commonly used for evaluation. In this study, we offer a solution: body-worn camera footage captures police–community interactions and how they might change as a function of training. Using this footage-as-data approach, we consider changes in officers’ communication following procedural justice training in Oakland, CA, USA, one module of which sought to increase officer-communicated respect during traffic stops. We applied natural language processing tools and expert annotations of traffic stop recordings to detect whether officers enacted the five behaviors recommended in this module. Compared with recordings of stops that occurred prior to the training, we find that officers employed more of these techniques in posttraining stops; officers were more likely to express concern for drivers’ safety, offer reassurance, and provide explicit reasons for the stop. These methods demonstrate the promise of a footage-as-data approach to capture and affect change in police–community interactions.