bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of antibiotic resistance mechanisms using a protein language model
Authors: Yagimoto Kanami , Hosoda Shion , Sato Miwa , Hamada Michiaki 
Published: September 2024

Abstract

Motivation
Antibiotic resistance has emerged as a major global health threat, with an increasing number of bacterial infections becoming difficult to treat. Predicting the underlying resistance mechanisms of antibiotic resistance genes (ARGs) is crucial for understanding and combating this problem. However, existing methods struggle to accurately predict resistance mechanisms for ARGs with low similarity to known sequences and lack sufficient interpretability of the prediction models.

Results
In this study, we present a novel approach for predicting ARG resistance mechanisms using ProteinBERT, a protein language model (pLM) based on deep learning. Our method outperforms state-of-the-art techniques on diverse ARG datasets, including those with low homology to the training data, highlighting its potential for predicting the resistance mechanisms of unknown ARGs. Attention analysis of the model reveals that it considers biologically relevant features, such as conserved amino acid residues and antibiotic target binding sites, when making predictions. These findings provide valuable insights into the molecular basis of antibiotic resistance and demonstrate the interpretability of pLMs, offering a new perspective on their application in bioinformatics.

Availability and implementation
The source code is available for free at https://github.com/hmdlab/ARG-BERT. The output results of the model are published at https://waseda.box.com/v/ARG-BERT-suppl.
Pooling controls from nested case–control studies with the proportional risks model
Authors: Chang Yen , Ivanova Anastasia , Albanes Demetrius , Fine Jason P , Shin Yei Eun 
Published: September 2024

Abstract
The standard approach to regression modeling for cause-specific hazards with prospective competing risks data specifies separate models for each failure type. An alternative proposed by Lunn and McNeil (1995) assumes the cause-specific hazards are proportional across causes. This may be more efficient than the standard approach, and allows the comparison of covariate effects across causes. In this paper, we extend Lunn and McNeil (1995) to nested case–control studies, accommodating scenarios with additional matching and non-proportionality. We also consider the case where data for different causes are obtained from different studies conducted in the same cohort. It is demonstrated that while only modest gains in efficiency are possible in full cohort analyses, substantial gains may be attained in nested case–control analyses for failure types that are relatively rare. Extensive simulation studies are conducted and real data analyses are provided using the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) study.
The influence of temperature and genomic variation on intracranial EEG measures in people with epilepsy
Authors: McNicholas Olivia C , Jiménez-Jiménez Diego , Oliveira Joana F A , Ferguson Lauren , Bellampalli Ravishankara , McLaughlin Charlotte , Chowdhury Fahmida Amin , Martins Custodio Helena , Moloney Patrick , Mavrogianni Anna , Diehl Beate , Sisodiya Sanjay M 
Published: September 2024

Abstract
Heatwaves have serious impacts on human health and constitute a key health concern from anthropogenic climate change. People have different individual tolerance for heatwaves or unaccustomed temperatures. Those with epilepsy may be particularly affected by temperature as the electroclinical hallmarks of brain excitability in epilepsy (inter-ictal epileptiform discharges and seizures) are influenced by a range of physiological and non-physiological conditions. Heatwaves are becoming more common and may affect brain excitability. Leveraging spontaneous heatwaves during periods of intracranial EEG recording in participants with epilepsy in a non–air-conditioned telemetry unit at the National Hospital for Neurology and Neurosurgery in London from May to August 2015–22, we examined the impact of heatwaves on brain excitability. In London, a heatwave is defined as three or more consecutive days with daily maximum temperatures ≥28°C. For each participant, we counted inter-ictal epileptiform discharges using four 10-min segments within, and outside of, heatwaves during periods of intracranial EEG recording. Additionally, we counted all clinical and subclinical seizures within, and outside of, heatwaves. We searched for causal rare genetic variants and calculated the epilepsy PRS. Nine participants were included in the study (six men, three women), median age 30 years (range 24–39). During heatwaves, there was a significant increase in the number of inter-ictal epileptiform discharges in three participants. Five participants had more seizures during the heatwave period, and as a group, there were significantly more seizures during the heatwaves. Genetic data, available for eight participants, showed none had known rare, genetically-determined epilepsies, whilst all had high polygenic risk scores for epilepsy. For some people with epilepsy, and not just those with known, rare, temperature-sensitive epilepsies, there is an association between heatwaves and increased brain excitability. These preliminary data require further validation and exploration, as they raise concerns about the impact of heatwaves directly on brain health.
Cerebral white matter damage in patients with end-stage kidney disease associates with cognitive impairment
Authors: Hou Yi-Chou , Tsai Chih-Chien , Chen Ruei-Ming , Liu Yi-Chien , Lu Kuo-Cheng , Chen Yao-Liang , Shen Ting-Wen , Wang Jiun-Jie 
Published: September 2024

ABSTRACT

Background
Damage to brain white matter often occurs in individuals with chronic kidney disease, which might be related to their cognitive decline. This study aims to investigate tract-specific white matter damage in patients with end-stage kidney disease by using fixel-based analysis.

Methods
Images of 31 end-stage kidney disease patients and 16 normal controls (aged: 61.1 ± 10.4 years; 11 men) were acquired from a 1.5T magnetic resonance scanner. The patients were subsequently divided into with normal cognition (N = 17, aged: 66.9 ± 7.2 years; 10 men) and cognitive impairment (N = 14, aged: 72.4 ± 9.4 years; 7 men). Cognitive assessment, and neurologic, hematologic and biochemical samples were collected. Fixel-based analysis was used to examine the tract-specific damage within white matter. Differences between groups were evaluated through connectivity-based fixel enhancement and non-parametric permutation testing. Correlation with biomarkers was conducted through general linear model. Significance was determined with family-wise error-corrected P-value &lt;.05.

Results
Reduced fixel-based metrics were observed in specific tract located the cerebral peduncle, internal capsule, corpus callosum, fornix and superior corona radiata in patients when compared with normal controls, indicating a reduction in fiber content. The fibers crossing the corpus callosum and the fornix/stria terminalis are particularly vulnerable sites, which can be associated with the decrease in both Mini-Mental State Examination (R2 ranged between 0.420 and 0.556) and Montreal Cognitive Assessment (R2 ranged between 0.425 and 0.509), as well as the plasma concentration of calcium (R2 ranged between 0.207 and 0.322). The plasma concentration of indoxyl sulfate was associated with the descending tracts from right posterior limb of internal capsule to cerebral peduncle (R2 ranged between 0.262 and 0.335).

Conclusions
Tract-specific white matter damage can be noticed in the patients with end-stage kidney disease, and could be associated with their cognitive decline.
Pulsed field ablation as a feasible option for the treatment of epicardial left ventricular summit premature complex foci near the coronary arteries: a case report
Authors: Spenkelink Dylan , van Wessel Harry , van Driel Vincent J , Ramanna Hemanth , van der Heijden Jeroen F 
Published: September 2024

Abstract

Background
Radiofrequency catheter ablation in the left ventricular summit region is a challenging procedure due to proximity to the coronary arteries. Pulsed field ablation, a novel non-thermal ablation modality, does not cause damage to coronary arteries and may be used in the left ventricular summit region.

Case summary
We describe a 45-year-old symptomatic patient with epicardial left ventricular summit premature ventricular complexes. Successful ablation of the focus was achieved by pulsed field ablation via a subxiphoid epicardial approach. Radiofrequency ablation would most likely have been ineffective due to the epicardial fat layer and potentially unsafe due to the proximity to the coronary arteries. Six months after ablation, the patient was asymptomatic and without ventricular ectopy.

Discussion
For the first time, epicardial pulsed field ablation was successfully used for ablation of left ventricular summit extrasystole, where radiofrequency ablation could not be used because of the proximity of the coronary arteries. We conclude that pulsed field ablation might be a feasible option for this indication.
Successful catheter ablation in an octogenarian with persistent atrial fibrillation complicated by cor triatriatum sinister: a case report
Authors: Okuyama Yusuke , Tamura Atsushi , Ueda Kohei , Matsuoka Shunzo , Nakagawa Yoshihisa 
Published: September 2024

Abstract

Background
Cor triatriatum sinister (CTS) is a rare congenital heart defect sometimes complicated with atrial fibrillation (AF). Catheter ablation (CA) relieves the AF-associated symptoms, but CA for AF with CTS has been reported rarely. Because CTS can be associated with other congenital heart disease, detailed preoperative assessment is important.

Case summary
An 80-year-old man was referred to our institution for shortness of breath that had persisted for 2 months when he was first diagnosed with AF. Transthoracic echocardiography revealed an enlarged left atrium (LA) divided into two chambers by a membrane. Transoesophageal echocardiography showed the membrane extending from the fossa ovalis (FO) to the Coumadin ridge, with the accessory (dorsal) chamber (AC) in closer proximity to the FO. Computed tomography showed that all pulmonary veins (PVs) flowed into the AC, with no PV anomalies. No other heart anomaly was identified, with no thrombus in the LA. With these findings, PV isolation (PVI) with CA was considered safe. Transseptal puncture was performed with intracardiac echocardiography for precise catheterization of the AC. Pulmonary vein isolation was performed successfully. The patient was discharged 4 days after the procedure, without any complications. His symptoms improved post-procedure, and sinus rhythm was maintained without antiarrhythmic drug therapy during the 18-month follow-up.

Discussion
Cor triatriatum sinister is a rare anomaly that accounts for 0.1% of all congenital heart diseases. Cor triatriatum sinister sometimes complicated with symptomatic AF. Detailed preoperative anatomical assessment with multiple imaging modalities helped us achieve safe and effective CA for a patient with AF and CTS, even in an octogenarian.
Multistep procedure for estimating non-linear soil response in low seismicity areas—a case study of Lucerne, Switzerland
Authors: Janusz Paulina , Bergamo Paolo , Bonilla Luis Fabian , Panzera Francesco , Roten Daniel , Loviknes Karina , Fäh Donat 
Published: September 2024

SUMMARY
The impact of non-linear soil behaviour on seismic hazard in low-to-moderate seismicity areas is often neglected; however, it may become relevant for long return periods. In this study, we used fully non-linear 1-D simulations to estimate the site-specific non-linear soil response in the low seismicity area, using the city of Lucerne in Switzerland as an example. The constitutive model considers the development of pore pressure excess and requires calibration of complex soil models, including the soil dilatancy parameters. In the absence of laboratory measurements, we mainly used the cone penetration test data to estimate the model variables and perform inversion for the dilatancy parameters. Our findings, using Swiss building code-compatible input ground motions, suggest a high probability of strong non-linear behaviour and the possibility of liquefaction at high ground motion levels in the case study area. While the non-linearity observations from strong-motion recordings are not available in Lucerne, the comparison with empirical data from other sites and other methods shows similarity with our predictions. Moreover, we show that the site response modelled is largely influenced by the strong pore pressure effects produced in thin sandy water-saturated layers. In addition, we demonstrate that the variability of the results due to the input motion and the soil parameters is significant, but within reasonable bounds.
Seismic traveltime tomography based on ensemble Kalman inversion
Authors: Li Yunduo , Zhang Yijie , Zhu Xueyu , Gao Jinghuai 
Published: September 2024

SUMMARY
In this paper, we present a new seismic traveltime tomography approach that combines ensemble Kalman inversion (EKI) with neural networks (NNs) to facilitate the inference of complex underground velocity fields. Our methodology tackles the challenges of high-dimensional velocity models through an efficient NN parametrization, enabling efficient training on coarse grids and accurate output on finer grids. This unique strategy, combined with a reduced-resolution forward solver, significantly enhances computational efficiency. Leveraging the robust capabilities of EKI, our method not only achieves rapid computations but also delivers informative uncertainty quantification for the estimated results. Through extensive numerical experiments, we demonstrate the exceptional accuracy and uncertainty quantification capabilities of our EKI-NNs approach. Even in the face of challenging geological scenarios, our method consistently generates valuable initial models for full wave inversion (FWI).
Return on investments in social determinants of health interventions: what is the evidence?
Authors: Nikpay Sayeh , Zhang Zhanji , Karaca-Mandic Pinar 
Published: September 2024

Abstract
There has been an increasing recognition of the importance and the value of addressing social determinants of health (SDOH) to improve population health outcomes, manage health care costs, and reduce health inequities. Despite the strong interest in investing in SDOH initiatives by various stakeholders, the literature on the return from such investments is scarce. The differences in study populations and methodologies, and the lack of data on SDOH intervention outcomes and/or costs, make it challenging to quantify and generalize outcomes for decision-making. We reviewed the literature on SDOH interventions focused on food and housing insecurity, and developed a methodology for estimating a key outcome: the return on investment (ROI), defined as the net returns from an intervention divided by its costs. The ROI estimates we report can be used by stakeholders to prioritize among alternative SDOH interventions for fundraising, investing, and implementing purposes. The average ROI for food-insecurity programs was 85% (ranging from 1% to 287%; except for 1 study‘s ROI, −31%) and for housing-insecurity programs was 50% (ranging from 5% to 224%; except for 1 ROI, −38%). In addition, these estimates can serve as key inputs for designing and employing innovative financing and policy solutions to increase the use of these interventions.
Converging functional phenotyping with systems mapping to illuminate the genotype–phenotype associations
Authors: Sun Ting , Shi Zheng , Jiang Rujia , Moshelion Menachem , Xu Pei 
Published: September 2024

Abstract
Illuminating the phenotype–genotype black box under complex traits is an ambitious goal for researchers. The generation of temporally or spatially phenotypic data today has far outpaced its interpretation, due to their highly dynamic nature depending on the environment and developmental stages. Here, we propose an integrated enviro-pheno-geno functional approach to pinpoint the major challenges of decomposing physiological traits. The strategy first features high-throughput functional physiological phenotyping (FPP) to efficiently acquire phenotypic and environmental data. It then features functional mapping (FM) and the extended systems mapping (SM) to tackle trait dynamics. FM, by modeling traits as continuous functions, can increase the power and efficiency in dissecting the spatiotemporal effects of QTLs. SM could enable reconstruction of a genotype–phenotype map from developmental pathways. We present a recent case study that combines FPP and SM to dissect complex physiological traits. This integrated approach will be an important engine to drive the translation of phenomic big data into genetic gain.
Economic Analyses for Disease Surveillance Planning and Advocacy
Authors: Hampton Lee M 
Published: September 2024

Abstract
Public health disease surveillance can guide a range of decisions related to the protection of populations. Economic analysis can be used to assess how surveillance for specific diseases can substitute for or complement other public health interventions and how to structure surveillance most efficiently. Assessing the value and costs of different disease surveillance options as part of broader disease prevention and control efforts is important for both using available resources efficiently to protect populations and communicating the need for additional resources as appropriate.
SARS-CoV-2 Variants May Affect Saliva RT-PCR Assay Sensitivity
Authors: Chwa Jason S , Shin Yunho , Lee Yesun , Fabrizio Thomas , Congrave-Wilson Zion , Cheng Wesley A , Jumarang Jaycee , Kim Minjun , Webby Richard , Bender Jeffrey M , Pannaraj Pia S 
Published: September 2024

Abstract

Background
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants demonstrate predilection for different regions of the respiratory tract. While saliva-based reverse transcription-polymerase chain reaction (RT-PCR) testing is a convenient, cost-effective alternative to nasopharyngeal swabs (NPS), few studies to date have investigated whether saliva sensitivity differs across variants of concern.

Methods
SARS-CoV-2 RT-PCR was performed on paired NPS and saliva specimens collected from individuals with acute coronavirus disease 2019 (COVID-19) symptoms or exposure to a COVID-19 household contact. Viral genome sequencing of NPS specimens and Los Angeles County surveillance data were used to determine the variant of infection. Saliva sensitivity was calculated using NPS-positive RT-PCR as the reference standard. Factors contributing to the likelihood of saliva SARS-CoV-2 RT-PCR positivity were evaluated with univariate and multivariable analyses.

Results
Between June 2020 and December 2022, 548 saliva samples paired with SARS-CoV-2 positive NPS samples were tested by RT-PCR. Overall, saliva sensitivity for SARS-CoV-2 detection was 61.7% (95% CI, 57.6%–65.7%). Sensitivity was highest with Delta infection (79.6%) compared to pre-Delta (58.5%) and Omicron (61.5%) (P = 0.003 and 0.01, respectively). Saliva sensitivity was higher in symptomatic individuals across all variants compared to asymptomatic cases [pre-Delta 80.6% vs 48.3% (P &lt; 0.001), Delta 100% vs 72.5% (P = 0.03), Omicron 78.7% vs 51.2% (P &lt; 0.001)]. Infection with Delta, symptoms, and high NPS viral load were independently associated with 2.99-, 3.45-, and 4.0-fold higher odds of SARS-CoV-2 detection by saliva-based RT-PCR (P = 0.004, &lt;0.001, and &lt;0.001), respectively.

Conclusions
As new variants emerge, evaluating saliva-based testing approaches may be crucial to ensure effective virus detection.
Impact of X-linked hypophosphatemic rickets/osteomalacia on health and quality of life: baseline data from the SUNFLOWER longitudinal, observational cohort study
Authors: Namba Noriyuki , Ito Nobuaki , Michigami Toshimi , Kang Hee Gyung , Kubota Takuo , Miyazaki Osamu , Shintani Ayumi , Kabata Daijiro , Nishida Yayoi , Fukumoto Seiji , Ozono Keiichi 
Published: September 2024

Abstract
The SUNFLOWER study was initiated in Japan and South Korea to clarify the course of X-linked hypophosphatemic rickets/osteomalacia (XLH); delineate its physical, mental, and financial burdens; and collect information on treatment. Here, we report cross-sectional data at the time of patient enrollment to better understand the real-world management and complications in patients with XLH and examine the effect of XLH on quality of life (QOL). This is an ongoing, longitudinal, observational cohort study of patients with a diagnosis of XLH. Data from 147 patients (118 in Japan and 29 in South Korea) were evaluated. In total, 77 children (mean age, 9.7 yr; 67.5% female) and 70 adults (mean age, 37.6 yr; 65.7% female) were enrolled. PHEX gene mutations were confirmed in 46/77 (59.7%) children and 37/70 (52.9%) adults. Most patients in both age groups were receiving a combination of phosphate and active vitamin D at baseline. The mean height Z-score was −2.21 among adults (male: −2.34; female: −2.14). The mean Rickets Severity Score in children was 1.62. Whereas children appeared to have low pain levels (mean revised faces pain scale score, 1.3), adults reported mild-to-moderate pain (mean Brief Pain Inventory pain severity, 2.02). Mean QOL in children (assessed using the 10-item short-form health survey for children) was low, with a score below normative level for physical functioning. In adults, results from the Western Ontario and McMaster Universities osteoarthritis index indicated the presence of pain, stiffness, and decreased physical function. The respective mean total days/year of work/school non-attendance due to symptoms/complications and management of XLH were 0.7 and 3.0 among adults, and 6.4 and 6.1 among children. Our findings reconfirmed a relationship between disease and QOL in patients with XLH. We anticipate that these data will be important in enabling clinicians to understand the daily reality of patients with XLH.
QTc prolongation across CDK4/6 inhibitors: a systematic review and meta-analysis of randomized controlled trials
Authors: Murad Bruno , Reis Pedro C A , Deberaldini Marinho Alice , Marin Comini Ana Carolina , Pinheiro Xavier Débora , Mella Soares Pessoa Beatriz , Raheem Farah , Ernst Brenda , Mina Lida A , Batalini Felipe 
Published: September 2024

Abstract

Background
Cyclin-dependent kinases (CDK) 4/6 inhibitors have significantly improved outcomes for patients with ER+/HER2− breast cancer. Nevertheless, they differ from each other in terms of chemical, biological, and pharmacological features, as well as toxicity profiles. We aim to determine whether QTc prolongation is caused by CDK4/6i in general or if it is associated with ribociclib only.

Methods
We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCTs) comparing the prevalence of QTc prolongation as an adverse event in HR+ breast cancer patients treated with CDK4/6i vs those without CDK4/6i. We pooled relative risk (RR) and mean difference (MD) with 95% confidence interval (CI) for the binary endpoint of QT prolongation.

Results
We included 14 RCTs comprising 16 196 patients, of whom 8576 underwent therapy with CDK4/6i. An increased risk of QTc prolongation was associated with the use of CDK4/6i (RR = 2.35, 95% CI = 1.67 to 3.29, P &lt; .001; I2 = 44%). Subgroup analyses revealed a significant increase in the QTc interval for the ribociclib and palbociclib cohorts. The ribociclib subgroup showed a relative risk of 3.12 (95% CI = 2.09 to 4.65, P &lt; .001; I2 = 12%), whereas the palbociclib subgroup had a relative risk of 1.51 (95% CI = 1.05 to 2.15, P = .025; I2 = 0%).

Conclusion
Palbociclib was associated with QTc prolongation; however, the relative risk for any grade QTc was quantitively twice with ribociclib. Furthermore, grade 3 QTc prolongations were observed exclusively with ribociclib. These results are important for guiding clinical decision-making and provide reassurance regarding the overall safety profile of this drug class.