bluuebunny/crossref_metadata_2025 huggingface dataset:
BS-clock, advancing epigenetic age prediction with high-resolution DNA methylation bisulfite sequencing data
Authors: Hu Congcong , Li Yunxiao , Li Longhui , Zhang Naiqian , Zheng Xiaoqi
Published: November 2024

Motivation

DNA methylation patterns provide precise and accurate estimates of biological age due to their robustness and predictable changes associated with aging processes. Although several methylation aging clocks have been developed in recent years, they are primarily designed for DNA methylation array data, which has limited CpG coverage and detection sensitivity compared to bisulfite sequencing data.

Results

Here, we present BS-clock, a novel DNA methylation clock for human aging based on bisulfite sequencing data. Using BS-seq data from 529 samples retrieved from four tissues, our BS-clock achieves higher correlations with chronological age in multiple tissue types compared to existing array-based clocks. Our study revealed age-dependent aging rates across different age stages and disease conditions, and overall low cross-tissue prediction capability by applying the model trained on one tissue type to others. In summary, BS-clock overcomes limitations of array-based techniques, offering genome-wide CpG site coverage and more robust and accurate aging quantification. This research paves the way for advanced epigenetic studies of aging and holds promise for developing targeted interventions to promote healthy aging.

Availability and implementation

All analysis codes for reproducing the results of the study are publicly available at https://github.com/hucongcong97/BS-clock.
How to achieve model-robust inference in stepped wedge trials with model-based methods?
Authors: Wang Bingkai , Wang Xueqi , Li Fan
Published: November 2024

A stepped wedge design is an unidirectional crossover design where clusters are randomized to distinct treatment sequences. While model-based analysis of stepped wedge designs is a standard practice to evaluate treatment effects accounting for clustering and adjusting for covariates, their properties under misspecification have not been systematically explored. In this article, we focus on model-based methods, including linear mixed models and generalized estimating equations with an independence, simple exchangeable, or nested exchangeable working correlation structure. We study when a potentially misspecified working model can offer consistent estimation of the marginal treatment effect estimands, which are defined nonparametrically with potential outcomes and may be functions of calendar time and/or exposure time. We prove a central result that consistency for nonparametric estimands usually requires a correctly specified treatment effect structure, but generally not the remaining aspects of the working model (functional form of covariates, random effects, and error distribution), and valid inference is obtained via the sandwich variance estimator. Furthermore, an additional g-computation step is required to achieve model-robust inference under non-identity link functions or for ratio estimands. The theoretical results are illustrated via several simulation experiments and re-analysis of a completed stepped wedge cluster randomized trial.
Wasserstein regression with empirical measures and density estimation for sparse data
Authors: Zhou Yidong , Müller Hans-Georg
Published: November 2024

The problem of modeling the relationship between univariate distributions and one or more explanatory variables lately has found increasing interest. Existing approaches proceed by substituting proxy estimated distributions for the typically unknown response distributions. These estimates are obtained from available data but are problematic when for some of the distributions only few data are available. Such situations are common in practice and cannot be addressed with currently available approaches, especially when one aims at density estimates. We show how this and other problems associated with density estimation such as tuning parameter selection and bias issues can be side-stepped when covariates are available. We also introduce a novel version of distribution-response regression that is based on empirical measures. By avoiding the preprocessing step of recovering complete individual response distributions, the proposed approach is applicable when the sample size available for each distribution varies and especially when it is small for some of the distributions but large for others. In this case, one can still obtain consistent distribution estimates even for distributions with only few data by gaining strength across the entire sample of distributions, while traditional approaches where distributions or densities are estimated individually fail, since sparsely sampled densities cannot be consistently estimated. The proposed model is demonstrated to outperform existing approaches through simulations and Environmental Influences on Child Health Outcomes data.
A case of biologic-resistant hand dermatitis demonstrates dual T2/T17 transcriptomic abnormalities and responds to Janus kinase inhibition
Authors: Taylor Mark A , Yuan Michelle , Wang Sijia , North Jeffrey P , Cheng Jeffrey B , Cho Raymond J
Published: November 2024

Many patients do not respond to targeted pathway-specific biologic therapies but predicting such failure remains an outstanding challenge. Here, in a case of adult-onset hand dermatitis that did not respond to multiple targeted biologic therapies, we detected gene expression programmes activated in both atopic dermatitis and psoriasis, via high-resolution genetic profiling. Broader, kinase-based immunosuppression elicited a near-complete clinical response. Therefore, our data suggest that such cases harbouring greater molecular complexity might be identified prospectively, circumventing some failures of single-pathway blockade.
Immunosuppression and transplantation-related characteristics affect the difference between eGFR equations based on creatinine compared to cystatin C in kidney transplant recipients
Authors: Weidmann Lukas , Laux Catherine , Castrezana Lopez Kai , Harmacek Dusan , George Britta , von Moos Seraina , Schachtner Thomas
Published: November 2024

Introduction

Previous studies show heterogeneity when applying estimated glomerular filtration (eGFR) equations to kidney transplant recipients (KTRs). However, research on the impact of transplantation-related characteristics on eGFR equations using creatinine (eGFRcr) compared to cystatin C (eGFRcys) is scarce.

Methods

We conducted a comprehensive analysis with three eGFRcr equations (Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009, European Kidney Function Consortium (EKFC) 2021, kidney recipient specific-glomerular filtration rate KRS-GFR) 2023), comparing them to two eGFRcys (CKD-EPI 2012 and EKFC 2023) in 596 KTRs. Bland–Altman plots demonstrated relative differences according to different eGFR-stages. Multivariable logistic regression identified transplantation-related characteristics independently associated with smaller or greater differences between eGFRcr and eGFRcys equations.

Results

94.3% of the cohort were White individuals. Median eGFR differed as much as 9 ml/min/1.73 m2 between equations. The median relative differences (Q2) were greater (more negative) when comparing the eGFRcr equations to eGFRcys CKD-EPI 2012, than when comparing them to eGFRcys EKFC 2023 (P < .001). Better average eGFR was associated with smaller mean relative differences in all comparisons but eGFRcr CKD-EPI 2009 with eGFR EKFC 2023 and eGFRcr EKFC 2021 with eGFRcys EKFC 2023. Living kidney donation and belatacept use were independent factors associated with a smaller difference (≥Q3) between eGFRcr and eGFRcys equations, while prednisone use or higher HbA1c were independently associated with a greater difference (≤Q1) between equations.

Conclusion

Different eGFR-stages, donor, or recipient characteristics, along with immunosuppression such as belatacept or prednisone, contribute to differences between eGFRcr and eGFRcys. These effects need to be considered in the clinical management of KTRs.
Predicting soccer matches with complex networks and machine learning
Authors: Baratela Eduardo Alves , Xavier Felipe Jordão , Peron Thomas , Ribeiro Villas-Boas Paulino , Rodrigues Francisco Aparecido
Published: November 2024

Soccer attracts the attention of many researchers and professionals in the sports industry. Therefore, the incorporation of science into the sport is constantly growing, with increasing investments in performance analysis and sports prediction industries. This study aims to (i) highlight the use of complex networks as an alternative tool for predicting soccer match outcomes and (ii) show how the combination of structural analysis of passing networks with match statistical data can provide deeper insights into the game patterns and strategies used by teams. In order to do so, complex network metrics and match statistics were used to build machine learning models that predict the wins and losses of soccer teams in different leagues. The results showed that models based on passing networks were as effective as ‘traditional’ models, which use general match statistics. Another finding was that by combining both approaches, more accurate models were obtained than when they were used separately, demonstrating that the fusion of such approaches can offer a deeper understanding of game patterns, allowing the comprehension of tactics employed by teams relationships between players, their positions and interactions during matches. It is worth mentioning that both network metrics and match statistics were important and impactful for the mixed model. Furthermore, the use of networks with a lower granularity of temporal evolution (such as creating a network for each half of the match) performed better than a single network for the entire game.
Epistemic authority in the digital public sphere. An integrative conceptual framework and research agenda
Authors: Bartsch Anne , Neuberger Christoph , Stark Birgit , Karnowski Veronika , Maurer Marcus , Pentzold Christian , Quandt Thorsten , Quiring Oliver , Schemer Christian
Published: November 2024

We develop an integrative conceptual framework and research agenda for studying epistemic authorities in the digital age. Consulting epistemic authorities (e.g., professional experts, well-informed laypeople, technologies) can be an efficient fast-track to knowledge. To fulfill this functional role, those who claim epistemic authority need to be both subjectively recognized (have a perceived advantage in knowledge) and objectively justified (have an actual advantage in knowledge). In a digital media context, new and unconventional knowledge sources have emerged that can fulfill the functional role of epistemic authorities. But false authorities that disseminate misinformation have emerged as well while other sources with important knowledge remain unrecognized. We further analyze the functional role of epistemic intermediaries that can mitigate such problematic developments by correcting false authorities and by providing endorsement for unrecognized authorities. We conclude with a research agenda to study functional forms of epistemic authorities and epistemic intermediaries in the digital public sphere.
Association between laryngopharyngeal reflux clinical scores and esophageal multichannel intraluminal impedance pH monitoring interpretation according to Lyon Consensus 2.0
Authors: Geeratragool Tanawat , Maneerattanaporn Monthira , Prapruetkit Jerdnaphang , Chuenprapai Pritsana , Chongkolwatana Cheerasook , Leelakusolvong Somchai
Published: November 2024

Laryngopharyngeal reflux remains a diagnostic challenge due to the lack of a definitive diagnostic tool. Esophageal multichannel intraluminal impedance (MII) pH monitoring has been proven reliable for detecting gastric reflux. This study aims to evaluate the association between clinical scores and MII/pH monitoring according to the Lyon Consensus 2.0. Patients with laryngo-pharyngeal symptoms (LPS) who had a reflux symptom index (RSI) ≥13 or reflux finding score (RFS) ≥7 underwent MII/pH monitoring. The findings were analyzed in comparison with clinical scores. A total of 100 patients meeting the inclusion criteria were recruited for this study. MII/pH monitoring revealed a median acid exposure time (AET) of 1.9% (interquartile range [IQR] = 0.2, 4.9), with 22% of patients recording an AET above 6%. The median number of reflux episodes was 29.5 episodes per day (IQR = 19.0, 43.8), with 7% experiencing more than 80 episodes per day. Gas reflux was identified as the most prevalent type. Based on the Lyon Consensus 2.0, 25 patients exhibited conclusive pathological reflux, while 75 patients showed no conclusive evidence of pathological reflux. No significant differences were found in RSI and RFS between these groups. Only gas reflux episodes showed a significant correlation with RSI (r = 0.255, P = 0.011). RSI and RFS among patients with LPS showed no statistically significant differences in identifying pathological reflux or no conclusive evidence of pathological reflux. This finding suggests that the pathophysiology underlying LPS may not be solely attributable to reflux.
Early recurrence of spontaneous coronary artery dissection: potential association with coronary vasospasm and optimal timing for spasm provocation test—a case series
Authors: Endo Toyohiro , Yunoki Kei , Miyahara Katsunori , Yamaguchi Satomi , Namba Yusuke , Yoshikawa Masaki , Oka Takefumi
Published: November 2024

Background

Spontaneous coronary artery dissection (SCAD) is an uncommon cause of acute coronary syndrome (ACS). Various factors predispose individuals to SCAD, including coronary vasospasm, which has been identified in some studies as a related factor.

Case summary

We present a series of three cases of ACS attributed to SCAD. Two cases involved early de novo recurrence potentially related to coronary spasm, and one case involved iatrogenic coronary artery dissection during a spasm provocation test.

Discussion

High recurrence rates of SCAD within 30 days of the initial event have been observed, although the effectiveness of pharmacologic therapy has not been conclusively established. While the administration of beta-blockers has been associated with a reduced risk of SCAD recurrence, their use may not be desirable in patients with coronary vasospasm. Detailed evaluations may be beneficial for patients where coronary vasospasm is suspected to tailor appropriate treatment strategies. Moreover, given the higher frequency of iatrogenic coronary artery dissection among patients with SCAD, careful consideration is needed to avoid high-risk periods when scheduling spasm provocation tests.
Anatomical vs. electrophysiological approach for ablation of premature ventricular contractions originating from the left ventricular summit (ISESHIMA-SUMMIT Study)
Authors: Watanabe Ryuta , Nagashima Koichi , Shirai Yasuhiro , Kitai Takayuki , Okada Takuya , Tokuda Michifumi , Fukunaga Masato , Onuki Koumei , Nakatani Yosuke , Yoshimura Shingo , Takatsuki Seiji , Hashimoto Kenji , Yamashita Shuhei , Kato Masafumi , Uchida Fumiya , Fukamizu Seiji , Hojo Rintaro , Mori Hitoshi , Matsumoto Kazuhisa , Kato Hiroyuki , Suga Kazumasa , Sakurai Taku , Sakamoto Yusuke , Hayashi Tatsuya , Wakamatsu Yuji , Hirata Shu , Hirata Moyuru , Sawada Masanaru , Kurokawa Sayaka , Okumura Yasuo
Published: November 2024

Aims

Catheter ablation (CA) of idiopathic ventricular arrhythmias (VAs) from the epicardial left ventricular summit is challenging. The endocardial approach targets two sites: the endocardial closest site (ECS) to the epicardial earliest activation site (epi-EAS) and the endocardial earliest activation site (endo-EAS). We aimed to differentiate between cases where CA at the ECS was effective and where CA at the endo-EAS yielded success.

Methods and results

Fifty-eight patients (47 men; age 60 ± 13 years) were analysed with VAs in which the EAS was observed in the coronary venous system (CVS). Overall, VAs were successfully eliminated in 42 (72%) patients: 8 in the CVS, 8 where the ECS matched with the endo-EAS, 11 at the ECS, and 15 at the endo-EAS. A successful ECS ablation was associated with a shorter epi-EAS–ECS distance (10.2 ± 4.7 vs. 18.8 ± 5.3 mm; P < 0.001) and shorter epi-EAS–left main coronary trunk (LMT) ostial distance (20.3 ± 7.6 vs. 30.3 ± 8.4 mm; P = 0.005), with optimal cut-off values of ≤12.6 and ≤24.0 mm, respectively. A successful endo-EAS ablation was associated with an earlier electrogram at the endo-EAS [23 (8, 36) vs. 15 (0, 19) ms preceding the QRS; P < 0.001] and shorter epi-EAS–endo-EAS interval [6 (1, 8) vs. 22 (12, 25) ms; P < 0.001], with optimal cut-off values of ≥18 and ≤9 ms, respectively.

Conclusion

Shorter anatomical distances between the epi-EAS and ECS, and between the epi-EAS and LMT ostium, predict a successful ECS ablation. The prematurity of the endo-EAS electrogram and a shorter interval between the epi-EAS and endo-EAS predicted a successful endo-EAS ablation.
Phylogenetic evaluation and genotypic identification of burn-related Pseudomonas aeruginosa strains isolated from post-burn human infections during hospitalization
Authors: Sanjar Fatemeh , Millan Claudia P , Leung Kai P
Published: November 2024

Cutaneous burn trauma, compromise of dermal layers and immune defense system is a physical and fiscal burden on healthcare systems. Burn-wound infections are a serious complication of thermal injury and contribute significantly to care burden. After burn-induced trauma, sepsis by Pseudomonas aeruginosa impairs patient recovery and contributes to mortality and morbidity. Past studies show positive correlation between detection of Pseudomonas species and healing-impaired traumatic wounds. Pseudomonas aeruginosa is a resilient opportunistic human pathogen and a nosocomial agent involved in pathology of healing-impaired wounds, especially in burn patients. Expansive array of virulence determinants has resulted in gentamicin- and silver-resistant P. aeruginosa outbreaks. Knowledge of molecular dynamics and phylogeny of P. aeruginosa associated with burn wounds is limited. Therefore, we conducted whole-genome sequencing for genotyping and phylogenetic analysis of P. aeruginosa burn-associated strains (n = 19) isolated from 7 burn cases during hospitalization. Comparison of genetic features in P. aeruginosa strains in the core genome and mobilome detected genetic variations within some clonal infections over time. Genetic variations were observed among different burn cases, with some features identified in severe lung infections. Polyclonal infections were also observed, with differing genotypes and virulence potentials, highlighting the importance of reasoned sampling of isolates for clinical testing.
Dynamic signatures: a mathematical approach to analysis
Authors: Okado Jessica Baleiro , da Camara e Silva Erick Simões , Sily Priscila Dias
Published: November 2024

This study evaluates mathematical tools (principal component analysis, dynamic time warping, and the Kolmogorov–Smirnov hypothesis test) to analyse global and local data from dynamic signatures to reduce subjectivity and increase the reproducibility of handwriting examination using a two-step approach. A dataset composed of 1 800 genuine signature samples, 870 simulated signatures, and 60 disguises (30 formally similar or “autosimulated” and 30 random but different from usual) provided by 30 volunteers was collected. The first step involved global data analysis using principal component analysis and a hypothesis test performed for 62 global characteristics, and associations of these characteristics were analysed through calculations of multivariate distance followed by a hypothesis test. The second step involved the analysis of local characteristics including vertical and horizontal positions, speed, pressure gradient, acceleration, and jerk point-to-point, by using dynamic time warping followed by a hypothesis test. Optimization of sensitivity and specificity metrics of the hypothesis test was explored by varying its stringency and observing accuracy rates for the simulated and genuine groups. A P-value threshold of 1 × 10−10 was found to be optimal, making the test more restrictive and yielding accuracy rates of 96.7% for genuine global data and 88.9% for simulated data. The same cut-off value for local characteristics provided an average accuracy rate of 95.4% for genuine samples and 94.7% for simulated samples, demonstrating high accuracy for both simulated and genuine samples. However, the method did not offer reasonable accuracy rates for disguises, consistent with observations in traditional handwriting examination. Our approach provided satisfactory results for forensic examination use. The visualization of graphs and signatures and analysis of all identifying elements of handwriting by the examining expert are still essential. In future studies, we plan to perform blind tests to validate our approach and propose a rigorous methodology.
Advances in the management of alcohol-associated liver disease
Authors: Anouti Ahmad , Kerr Thomas A , Mitchell Mack C , Cotter Thomas G
Published: November 2024

Alcohol-associated liver disease (ALD) is a significant global health challenge, encompassing a spectrum from steatotic liver disease to cirrhosis and alcohol-associated hepatitis, and contributed to 25% of global cirrhosis deaths in 2019. The identification of both modifiable (e.g. heavy drinking, metabolic syndromes) and non-modifiable risk factors (e.g. genetic predispositions) is crucial for effective disease management. Alcohol use assessment and treatment, by using both behavioral therapy and pharmacotherapeutic modalities, nutrition support, and optimization of liver disease modifiers, form the cornerstone of management. Advances in medical therapies, such as fecal microbiota transplantation and novel agents such as IL-22, are being explored for their therapeutic potential. A unifying theme in ALD care is the need for a personalized approach to management, accounting for the spectrum of the disease and individual patient characteristics, to tailor interventions effectively. Finally, it is essential to address the challenges to effective ALD treatment, including socioeconomic, logistical, and stigma-related barriers, to improve patient outcomes. This review discusses the current knowledge on ALD, including epidemiology, pathophysiology, risk factors, and management strategies, highlighting the critical role of integrated care models.
Ambient noise surface-wave imaging in a hardrock environment: implications for mineral exploration
Authors: Wilczynski Zbigniew , Kaslilar Ayse , Malehmir Alireza , Manzi Musa , Vivin Lilas , Lepine Jean , Valishin Oleg , Högdahl Karin
Published: November 2024

The advancement of seismic methods is vital for mineral exploration in the ongoing energy transition. In this study, we investigate the application of ambient noise seismic interferometry and surface-wave analysis to characterize the subsurface in a mineral exploration context. We then confirm the results of the passive seismic investigation through an active source experiment. We collected ambient noise data using a 2-D seismic line initially deployed for an active source reflection seismic study. By cross-correlating the signals, we retrieved the surface waves and constructed a 2-D shear-wave velocity profile using conventional surface-wave analysis. We utilized the active source data to establish initial assumptions about the surveyed medium and then validated the passive seismic experiment. The passive seismic results are concordant with the active source results and allow for the interpretation of geological contacts and fault zones. Our work demonstrates the potential of passive seismic methods for investigating local tectonic settings and their role in hardrock mineral exploration.
Teleseismic virtual-source reverse time migration of upper crustal structures in the Three Gorges region, China
Authors: Zou Zhihui , Zhou Hua-Wei , Fang Lihua , Kuang Wenhuan , Pei Jianxin
Published: November 2024

The Three Gorges (TG) in central China is an earthquake prone region that lacks active-source seismic surveys, hence requiring high-resolution passive seismic imaging to reveal crustal structures in detail. While teleseismic virtual-source reflection (TVR) profiling is effective for imaging gently dipping upper crustal structures, it is unsuitable for mapping steep structures beneath rugged topography in the TG region. Here we develop a teleseismic virtual-source reverse time migration (TV-RTM) to improve the imaging of steep structures. Synthetic tests are conducted to demonstrate the validity and resolution of the TV-RTM method. To mitigate the imaging inaccuracy due to sparse station spacing, we interpolate direct-arrival waveforms to achieve a doubling of the minimally required station spacing from 2 to 4 km. The TV-RTM images of the upper crustal structure beneath a 2-D array in the TG region reveal significant fold and thrust structures that correlate well with the surface geology and tectonic framework. The resolution of the images is assessed using 2-D and 3-D synthetic models with the station and source geometry of field data. The TV-RTM method provides a new passive seismic solution for studying upper crustal structures in regions that lack active-source seismic data.
The diversity of glycan chains in jellyfish mucin of three Cubozoan species: the contrast in molecular evolution rates of the peptide chain and Glycans
Authors: Kaneko Takuma , Tanaka Shinra , Sugiyama Minami , Kaise Shiori , Inui Hiroshi , Ushida Kiminori
Published: November 2024

The O-glycan composition of jellyfish (JF) mucin (qniumucin: Q-mucin) extracted from three Cubozoan species was studied after the optimization of the purification protocol. Application of a stepwise gradient of ionic strength to anion exchange chromatography (AEXC) was effective for isolating Q-mucin from coexisting impurities. In the three species, the amino acid sequence of the tandem repeat (TR) region in Q-mucin in all three Cubozoans seemed to remain the same as that in all Scyphozoans, although their glycan chains seemed to exhibit clear diversity. In particular, the amounts of acidic moieties on the glycan chains of Q-mucin from the Cubozoans markedly varied even in these genetically close species. In two of the three Cubozoan species, the fraction of disaccharides was large, showing a sharp contrast to that of the glycans of Q-mucin in Scyphozoans. This study also indicates that the simple sequence of TR commonly inherited in all Cubozoan and Scyphozoan JF species after the long term of evolution over 500 M years. According to this research, the glycans and the TR of mucin-type glycoproteins (MTGPs), forming a hierarchical structure, appear to complement each other in the evolutionary changes because the time required for their hereditary conversion is considerably different. The cooperation of these mechanisms is a strategy to achieve the contradictory functions of biosystems, namely species conservation and diversity acquisition.
Dynamic response analysis of a floating bridge structure under combined actions from seismic loading and waves at different incident angles
Authors: Wang Piguang , Xu Haoran , Shen Yiming , Qu Yang , Du Xiuli
Published: November 2024

This article investigates the complex-coupled response of a cross-sea floating bridge under the combined actions of seismic loading and wave at different incident angles. The bridge structure is modeled using the finite element method, considering the interaction between the girder, pier, pontoon, and mooring chains. Wave forces are calculated based on potential theory, and an added mass approach is applied to simulate the hydrodynamic forces induced by the earthquake. Simulations were conducted using a 1-year random wave at three different incident angles of 0o, 45o, and 90o, combined with three-dimensional seismic loading of varying magnitudes: 0.3, 0.5, and 1 g. The simulation results indicate that the direction of the incident wave significantly influences the bridge’s response. The coupling effect between wave and seismic forces on the floating bridge’s response is not simply additive. Generally, when the earthquake magnitude is low, the wave loading significantly impacts the bridge’s dynamics. However, as the earthquake magnitude increases, the bridge’s response becomes dominated by the seismic forces, rendering the influence of wave forces negligible.
Prolonged sitafloxacin and doxycycline combination regimen for treating infections by highly resistant Mycoplasma genitalium
Authors: Ando Naokatsu , Mizushima Daisuke , Takano Misao , Mitobe Morika , Kobayashi Kai , Kubota Hiroaki , Miyake Hirofumi , Suzuki Jun , Sadamasu Kenji , Aoki Takahiro , Watanabe Koji , Oka Shinichi , Gatanaga Hiroyuki
Published: November 2024

Background

Mycoplasma genitalium, which causes sexually transmitted diseases, is increasingly resistant to key antibiotics such as macrolides and quinolones, posing a challenge for treatment.

Objectives

To assess the effectiveness of prolonged sitafloxacin and doxycycline combination therapy as a new alternative treatment strategy for highly drug-resistant M. genitalium strains

Methods

A prospective cohort study was conducted at the National Center for Global Health and Medicine, Tokyo, Japan, from 1 January 2020 to 31 October 2022. Patients with M. genitalium urogenital or rectal infections and those who did not receive the initial sitafloxacin monotherapy were included. Patients were administered sitafloxacin and doxycycline for 21 days as salvage therapy. M. genitalium isolates were tested for parC, gyrA and 23S rRNA resistance-associated mutations.

Results

Twenty-seven patients received the combination therapy. All M. genitalium strains available for resistance analysis had parC (24/24) and macrolide resistance-associated (25/25) mutations, and 68% (17/25) had gyrA mutations. The overall cure rate was 77.8%. For strains with concurrent parC and gyrA mutations, the cure rate was 68.8% (P = 0.053) compared with that for monotherapy (37.5%).

Conclusions

Prolonged combination therapy is highly effective against M. genitalium strains with concurrent parC and gyrA mutations. Future research should focus on establishing the optimal treatment duration and monitoring the risk of resistance.
Associations between neighbourhood-level median household income and outpatients’ risk of antibiotic non-susceptible uropathogens in a major urban centre, USA
Authors: Mwansa Chanda M L , Babiker Ahmed , Satola Sarah , Logan Latania K , Nadimpalli Maya L
Published: November 2024

Introduction

Resistance to first-line antibiotics among urinary tract infections continues to rise, but how neighbourhood-level socioeconomic status impacts this risk remains unclear. We examined the effect of neighbourhood-level income on a patient’s risk of having a uropathogen non-susceptible to trimethoprim/sulfamethoxazole (TMP/SMX) or nitrofurantoin.

Methods

We used electronic health record data and antibiotic susceptibility test results for urinary Escherichia coli and Klebsiella pneumoniae collected at Emory Healthcare outpatient facilities in greater Atlanta between October 2022 and September 2023. We determined patients’ block group median household income (MHI) using their residential addresses and 2017–21 US census data. We performed a logistic regression with a priori risk factors using a generalized estimating equation, with subgroup analysis by organism and for patients with diabetes mellitus.

Results

We included 9325 urine E. coli and K. pneumoniae isolates from 3867 outpatients. Compared to uropathogenic E. coli, K. pneumoniae were more likely to be non-susceptible to nitrofurantoin (P < 0.001) and less likely to be non-susceptible to TMP/SMX (P < 0.001). Compared to the lowest MHI quintile, patients in the highest MHI quintile neighbourhoods had 0.78 odds of harbouring a non-susceptible uropathogen (95% CI: 0.64, 0.95) after controlling for patient age, sex and race/ethnicity, along with neighbourhood-level characteristics. This association was stronger for K. pneumoniae infections and non-significant among people with diabetes.

Conclusions

Higher neighbourhood-level MHI was associated with lower individual risk of harbouring a first-line antibiotic-non-susceptible uropathogen.
Possible role of bone turnover markers in the diagnosis of adult hypophosphatasia
Authors: Bertoldo Francesco , Tripepi Giovanni , Zaninotto Martina , Plebani Mario , Scillitani Alfredo , Varenna Massimo , Crotti Chiara , Cipriani Cristiana , Pepe Jessica , Minisola Salvatore , Pugliese Flavia , Guarnieri Vito , Baffa Valeria , Torres Marco Onofrio , Zanchetta Francesca , Fusaro Maria , Rossini Maurizio , Brandi Maria Luisa , Egan Colin Gerard , Simioni Paolo , Arcidiacono Gaetano Paride , Sella Stefania , Giannini Sandro
Published: November 2024

Hypophosphatasia (HPP) is a rare disorder of the bone metabolism, characterized by genetically determined low alkaline phosphatase (ALP) activity. Low ALP may also be observed in some common causes of bone fragility, such as in osteoporosis treated with antiresorptive drugs. This study aimed to verify whether differences in bone turnover markers (BTMs) could help differentiate adult patients with HPP from those with osteoporosis undergoing antiresorptive treatment. In this multicenter study, we enrolled 23 adult patients with a diagnosis of HPP and compared them with 46 osteoporotic subjects previously treated with zoledronic acid or denosumab. BTMs such as CTX, N-terminal propeptide of type I procollagen (P1NP), total ALP, and bone ALP (bALP) were measured, and ratios between BTMs were also calculated. Considering that the control group included only females, in the primary analysis we compared their characteristics with that of the 16 female patients with HPP. Both individual BTMs (CTX and P1NP) and 4 BTM ratios (ALP/P1NP, bALP/P1NP, ALP/CTX, and bALP/CTX) showed satisfactory discriminatory power, outperforming ALP alone. P1NP, in particular, had an area under the curve (AUC) of 0.962 with a cut-off of 32 μg/L, while as for the BTMs ratios, the ALP/P1NP ratio had an AUC of 0.964 with a cut-off of 1.114. Similar results were confirmed when including male HPP patients, when adjusting for age and sex, and finally when performing a sensitivity analysis only in patients with ALP less than or equal to 32 U/L (ie, the median of the distribution of the entire population). In cases of low ALP and bone fragility, BTM and their ratios could help distinguish HPP patients from osteoporotic individuals treated with antiresorptive drugs, aiding in accurate diagnosis and reducing the risk of inappropriate treatment.
An industrial robot-based sawing method for natural stone sculpture
Authors: Zhang Zhen , Yin Fangchen , Huang Hui , Huang Guoqin , Cui Changcai
Published: November 2024

In order to enhance the efficiency of stone sculpture machining while reducing natural stone waste and environmental pollution, a method for the efficient and green sawing of natural stone sculptures using industrial robots is proposed. The model contour is used as the directrix of the ruled surface to construct a ruled surface model that minimizes volume. The contour curve corresponding to this minimized-volume ruled surface model serves as the machining path for an integrated robotic diamond wire cutting system. A ruled surface model of Stanford Bunny was obtained by sawing a marble block using the robotic diamond wire cutting system. The experimental results show that the material removal rate of the robotic diamond wire cutting is 1.37 times that of saw blade cutting and 2.30 times that of grinding. The volume of stone powder generated during the processing was 0.16×10⁷mm³, accounting for only 1.47% of the total stone powder produced during the grinding process. In summary, the proposed method not only enhances processing efficiency but also reduces natural stone waste and mitigates environmental pollution.
Demographic parameters of Pachycrepoideus vindemiae (Hymenoptera: Pteromalidae) reared on Drosophila suzukii (Diptera: Drosophilidae), Ceratitis capitata (Diptera: Tephritidae), and Anastrepha fraterculus (Diptera: Tephritidae) puparia
Authors: Garcez Amanda M , Krüger Alexandra P , Nava Dori E
Published: November 2024

Pachycrepoideus vindemiae (Rondani) is a solitary generalist pupal ectoparasitoid that parasitizes dipterans of various families and genera. This study aimed to evaluate Anastrepha fraterculus (Wiedemann), Ceratitis capitata (Wiedemann), and Drosophila suzukii (Matsumura) to determine the best host for the development and mass production of parasitoid P. vindemiae in the laboratory. The experiments were performed in air-conditioned rooms at a temperature of 25 ± 2 °C, relative humidity of 70% ± 10%, and photophase of 12 h. Moreover, 24-h-old pupae of A. fraterculus, C. capitata, and D. suzukii were provided daily to 25 pairs of the parasitoid. The following parameters were determined: percentage of parasitism, percentage of emergence, hind tibia size, sex ratio, and longevity. A fertility life table was established using biological data. Notably, P. vindemiae parasitized the pupae of all 3 hosts but did not affect the sex ratio of the offspring. Parental parasitoids from the pupae of A. fraterculus and C. capitata lived longer than those from the pupae of D. suzukii. However, for all other parameters, parasitoids from D. suzukii showed better performance than those from other hosts, with shorter intervals between generations (T) and a higher net reproduction rate (Ro), intrinsic rate of increase (rm), and finite rate of increase (λ).
Axiomatization of Boolean Connexive Logics with syncategorematic negation and modalities
Authors: Jarmużek T , Malinowski J , Parol A , Zamperlin N
Published: November 2024

In the article we investigate three classes of extended Boolean Connexive Logics. Two of them are extensions of Modal and non-Modal Boolean Connexive Logics with a property of closure under an arbitrary number of negations. The remaining one is an extension of Modal Boolean Connexive Logic with a property of closure under the function of demodalization. In our work we provide a formal presentation of mentioned properties and axiom schemata that allow us to incorporate them into Hilbert-style calculi. The presented axiomatic systems are provided with proofs of soundness, completeness and decidability. The properties of closure under negation and demodalization are motivated by the syncategorematic view on the connectives of negation and modalities, which is discussed in the paper.
Resolution of IP disputes in Turkey: emerging trends of mandatory mediation and specialized courts for IP disputes
Authors: Kaya Serkan , Kervankıran Emrullah , Akıncı Muhammed Furkan
Published: November 2024

Resolving IP disputes is a critical challenge within the intricate framework of global business and innovation. Turkey, amidst its evolving legal landscape, has shown considerable attention towards efficiently managing disputes linked to IP rights. Notably, Turkey has significantly transformed its approach to handling these issues by introducing specialized IP courts and embracing mandatory mediation as a resolution method. The adoption of mandatory mediation in Turkey marks a notable departure from traditional litigation approaches, aiming to expedite disputes and resolve them in a cost-effective manner. Additionally, the establishment of dedicated IP courts signals a deliberate shift towards adjudication grounded in specialized knowledge tailored to address the intricate nuances of IP conflicts. This article seeks to delve into the burgeoning trends and evolving practices surrounding IP courts and mandatory mediation to resolve IP disputes within the Turkish jurisdiction. By examining the historical foundations, legislative developments and practical applications of mandatory mediation in the context of IP disputes, this study aims to provide an insightful evaluation of the efficacy and feasibility of these mechanisms while exploring their implications for stakeholders.
Identifying physicians’ needs in community-based palliative care consultation for cancer patients in palliative care specialist-deficient settings: a qualitative study
Authors: Aoki Miwa , Yamamoto Sena , Takao Ayumi , Tamura Saori , Kizawa Yoshiyuki , Arao Harue
Published: November 2024

Background

Consultation with palliative care specialists can be beneficial in addressing the numerous demands of patients with cancers and their families within communities. In settings lacking palliative care specialists, establishing a new community-based palliative care consultation system necessitates gathering evidence to support its development. This study aimed to identify the specific palliative care consultation needs and the consultation methods requested by Japanese physicians in settings without palliative care specialists.

Methods

A qualitative descriptive study utilizing semi-structured virtual interviews. From August 2023 to October 2023, we conducted interviews with 11 physicians providing cancer treatment in hospitals or clinics in a prefecture within the Kanto region of Japan without palliative care specialists. Participants were asked about the specific palliative care consultation needs they have and the need for consultation methods.

Results

Of the 11 physicians, nine had completed the nationwide basic primary palliative care education program. The survey revealed three themes regarding their consultation needs: ‘receiving specialized insight’, ‘inspiring confidence’, and ‘improving care capacity’, Two themes emerged regarding the need for consultation methods: ‘enhancing care collaboration’ and ‘improving accessibility’.

Conclusions

Physicians require consultation systems to empower them and enhance the community care capacity, in addition to providing specialized knowledge. These systems would include collaboration with specialists through outreach consultations, utilization of information and communications technology, and the establishment of nurse-led consultation teams to improve access to palliative care teams.
The Diverse Aspects of Uterine Serous Cancer: an NCI workshop on the status of and opportunities for advancement of research
Authors: Janakiram Naveena B , Clarke Megan A , Kai Mihoko , Wallace Tiffany A , Russo Sandra , Hecht Toby T , Kohn Elise C , Heckman-Stoddard Brandy
Published: November 2024

The marked increase in the incidence and mortality associated with endometrial cancer over the past 2 decades is driven in part by rising rates of higher-grade, more aggressive endometrial cancers with variations in TP53, uterine serous cancers and their dedifferentiated component, uterine carcinosarcomas. Uterine serous cancer rates have been increasing among all racial and ethnic groups, with higher rates of this aggressive uterine cancer in Black women. The National Cancer Institute hosted a workshop in June 2023 to examine the diverse aspects of uterine serous cancers across epidemiology, biology, and molecular genetics and to advance knowledge from basic to preclinical and translational efforts. Key stakeholders, including basic scientists, clinical investigators, and patient advocates, came together to identify critical research gaps that, when addressed, would facilitate more comprehensive and rapid progress in understanding and ultimately treating uterine serous cancers across all patients. The National Cancer Institute released a supplemental funding opportunity (NOT-CA-24-044) in spring 2024 to facilitate rapid translation of these recommendations.
Use of radiofrequency ablation of the vaginal canal for genitourinary syndrome of menopause
Authors: Rothenberger Rodger , Kopinga Elaine , Dell Jeffrey , Moore Robert D , Miklos John R , Karram Mickey
Published: November 2024

Background

Genitourinary syndrome of menopause (GSM) is a prevalent condition with a constellation of symptoms including burning, dryness, dyspareunia, and irritative lower urinary tract symptoms that result from vulvovaginal atrophic changes. Though hormonal therapy is a mainstay of treatment in GSM, some patients may pursue nonhormonal therapies.

Aim

To determine the efficacy of radiofrequency ablation of the vaginal canal with the MorpheusV applicator in reducing the symptoms of GSM.

Methods

We conducted a multicenter prospective case series of women with GSM as confirmed by Vaginal Health Index Score (VHIS). Subjects received 3 treatments of radiofrequency ablation ~4 weeks apart with follow-up to 6-month posttreatment.

Outcomes

The primary endpoint was VHIS at 6-month posttreatment. Secondary endpoints were VHIS at 3 months, Visual analog scale (VAS) pain with each treatment, 3- and 6-month measurements of urogenital distress inventory-6 (UDI-6), and female sexual function index (FSFI) questionnaires.

Results

From 2021 to 2023, 71 women were enrolled in the study with 51 followed to the 6-month follow-up time point. Treatments were found to be low in VAS pain score with mean values of 2.13 ± 2.1, 2.55 ± 2.38, and 2.18 ± 2.14 at treatments 1, 2, and 3 respectively. An improvement in VHIS score was seen from baseline to 3 months after the last treatment (15.00 ± 5.37 vs. 19.62 ± 4.44) and sustained at 6 months (20.23 ± 4.12) (P < .001). Significant improvements in both UDI-6 and FSFI were also noted. Between baseline and 6 months after treatment (FSFI: 18.81 ± 9.57 vs. 22.81 ± 10.34, P < 0.001; UDI-6: 39.58 ± 15.98 vs. 22.42 ± 14.03, P < 0.001). No adverse events were encountered by any subject during this study.

Clinical implications

A therapy that is safe and effective in the treatment of both GSM and lower urinary tract symptoms without the use of hormonal methods is clinically impactful for the many patients who cannot receive or do not desire to receive these medications.

Strengths and limitations

Strengths of this study include the utilization of 3 treatment sessions, with follow-up of subjects to 6-month posttreatment with a comprehensive assessment of patient symptoms. Limitations include the unblinded nature of the study and the lack of a comparator group.

Conclusion

The data from this study suggests that radiofrequency ablation of the vaginal canal by the MorpheusV applicator is a safe and effective intervention for GSM. It also shows subjective improvements in stress urinary incontinence, urge urinary incontinence, and sexual function.
Mitigation of chemotherapy-induced experimental intestinal mucositis through postbiotic lactate
Authors: Matos Isabel David , Borges Amanda Dias , Trindade Luísa Martins , Andrade Maria Emília Rabelo , Cavalcante Gregório Grama , Leocádio Paola Caroline Lacerda , Alvarez-Leite Jacqueline Isaura , Cassali Geovanni Dantas , Costa Bruno Galotti , Martins Flaviano dos Santos , Cardoso Valbert Nascimento , Generoso Simone de Vasconcelos
Published: November 2024

Postbiotic lactate modulates the immune system in inflammatory bowel diseases. However, its role in experimental intestinal mucositis (IM) has not been elucidated. This study aimed to evaluate the effects of lactate supplementation (1 and 2 × 10−1 mol/l) in a 5-fluorouracil (5-FU)-induced IM model. Male BALB/c mice (6–8 weeks old) were randomly divided into four groups: control (CTL), mucositis (MUC), mucositis with 1 × 10−1 mol/l lactate solution (MUC10), and mucositis with 2 × 10−1 mol/l lactate solution (MUC200). Lactate was administered via oral gavage for 10 days. Following the treatment period, the animals were subjected to an intraperitoneal injection of 300 mg/kg 5-FU to induce IM and were euthanized 72 h later for analysis. The MUC group presented intestinal damage with a poor histological score and decreased morphometric parameters as well as decreased mucus production and increased inflammatory infiltration and intestinal permeability compared to those of the CTL group (P < .05). However, the MUC200 group exhibited better results for the evaluated parameters than the MUC group (P < .05). Notably, the results in the MUC10 group were similar to those in the MUC group (P > .05). In conclusion, lactate supplementation attenuates mucositis-induced damage in a dose-dependent manner.