bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyber security analysis of connected vehicles
Authors: Mwanje Maria Drolence , Kaiwartya Omprakash , Aljaidi Mohammad , Cao Yue , Kumar Sushil , Jha Devki Nandan , Naser Abdallah , Lloret Jaime
Published: April 2024

The sensor‐enabled in‐vehicle communication and infrastructure‐centric vehicle‐to‐everything (V2X) communications have significantly contributed to the spark in the amount of data exchange in the connected and autonomous vehicles (CAV) environment. The growing vehicular communications pose a potential cyber security risk considering online vehicle hijacking. Therefore, there is a critical need to prioritize the cyber security issues in the CAV research theme. In this context, this paper presents a cyber security analysis of connected vehicle traffic environments (CyACV). Specifically, potential cyber security attacks in CAV are critically investigated and validated via experimental data sets. Trust in V2X communication for connected vehicles is explored in detail focusing on trust computation and trust management approaches and related challenges. A wide range of trust‐based cyber security solutions for CAV have been critically investigated considering their strengths and weaknesses. Open research directions have been highlighted as potential new research themes in CAV cyber security area.
Real‐time multi‐objective speed planning ATO considering assist driving for subway
Authors: Wang Xiaowen , Zhang Zipei , Wang Qingyuan , Sun Pengfei , Feng Xiaoyun
Published: April 2024

Speed curve planning is one of the most important functions of automatic train operation (ATO). To improve the real‐time optimization capability and driver‐friendliness of the existing ATO, an extended ATO framework considering both automatic driving and assisted driving is designed. A multi‐objective optimization model based on quadratic programming is established considering energy‐saving, punctuality, and comfort. However, due to the influence of the weight of multi‐objectives, this method cannot directly obtain the speed curve satisfying the trip time constraint. Further, based on the analysis about the weight of multi‐objects, a time‐constrained quadratic programming algorithm is proposed. With the proposed method, the speed curve can be calculated in real‐time both before operations and during operations. For the former, time‐varying train mass and trip time are considered to guarantee an optimal solution. For the latter, deviations, delays, and maloperations on the way are corrected. Simulation experiments verify the solvability and real‐time performance of the proposed method. In particular, compared with the dynamic programming and (mixed‐integer linear programming) MILP method, the proposed method is more energy‐efficient and easier to be followed by the driver. In addition, a prototype is developed for commercial tests on a Beijing subway line. The relevant performance is verified in commercial tests.
Flexible optimal bus‐schedule bridging for metro operation‐interruption
Authors: Lai Yuanwen , Liang Jianhong , Rao Yinsheng , Fan Yanhui , Zhan Renyan , Easa Said , Wang Shuyi
Published: April 2024

Under the sudden interruption of the metro, it is significant to dispatch emergency bridging buses to evacuate stranded passengers to improve linkage management and service reliability. Aiming at the problem of emergency bridging bus scheduling, considering the remaining capacity of conventional buses, passenger tolerance, and site convenience, a flexible combined emergency bridging bus scheduling model is constructed based on the constraints of vehicle capacity, dispatching capacity, and maximum evacuation times of emergency bridging bus, aiming at minimizing the maximum evacuation time and passenger delay. The improved Harris hawk algorithm is used to solve the model, and the evacuation plan of the demand‐responsive and station‐station bridging lines is obtained. The maximum evacuation time is 41 min, and the average delay of stranded passengers is 19 min. The results show that the maximum evacuation time is 10% and 27% less than the fixed combined and single scheduling. The average delay is 16% and 42% less than the fixed combination and traditional single scheduling. The sensitivity analysis of the influencing factors of emergency bridging bus scheduling is conducted. The results show that the flexible combined emergency bridging bus scheduling model constructed in this paper can improve evacuation efficiency and reduce passenger travel delays.
A novel algorithm for open switch fault detection and fault tolerant control of interleaved DC‐DC boost converters
Authors: Zandi Omid , Poshtan Javad
Published: April 2024

This paper presents a novel algorithm for fault diagnosis and fault tolerant control of interleaved boost converters (IBCs) in the presence of single or double simultaneous open‐circuit faults (OCFs) in power switches. An innovative diagnosis signal (recorded by a cheap current sensor) will be introduced whose waveform mainly depends on the healthy or faulty condition of the converter. Since the diagnosis signal is periodic in the steady‐state operation of the converters, its Fourier Series coefficients, together with the duty cycle of the converter are used as distinguishing features for fault diagnosis of the OCFs in the converter. The well‐known Kalman filter is utilized for robust estimation of the Fourier‐based features. Finally, the modulation of the remaining healthy phases is rearranged in a way that the pre‐fault performance recovers. The proposed algorithm is verified in a laboratory four‐phase IBC setup in which the experimental results show its satisfactory performance. Also, the structure of the proposed method is straightforward and can be implemented in the same microcontroller which is used for voltage and current regulation of the converter.
De-risking pension plans: the impact on firm value from lump-sum buyouts
Authors: Jorgensen Randy , Obonyo Tirimba , Wingender John R.
Published: April 2024

Firms have attempted to de-risk their pension obligations by offering its pension beneficiaries a lump-sum distribution instead of the guaranteed payments to be paid to retirees in a defined benefit pension plan. We examine the stock market reaction to the announcement of these offerings using event study methodologies. We find a statistically significant positive cumulative abnormal returns for the 20-day period prior to the event, the 20-day period after the event, and for the entire 41-day event period surrounding the announcement. We also find that the cumulative abnormal returns are higher the more liabilities a firm has and increases with the level of funding of the pension plan. Our results contribute to the literature on pensions by finding that firms that buy out their pensioners’ defined benefit payments via a lump-sum distribution experience an increase in firm value. There is a significant amount of analysis of such buyouts in the literature and in the press, but our results are the first to examine and document the increase in value derived from such pension changes. We also more fully develop the motivations for such events from a cost/benefit perspective.
Career decisions in artistic professions during the COVID-19 pandemic in Germany—an experimental study
Authors: Seitz Matthias , Frick Ulrich , Tallon Miles , Gotthardt Karina , Rakoczy Katrin
Published: April 2024

The COVID-19 pandemic has had a significant impact on the professional situation in artistic professions. Repeated lockdowns resulted in the cancellation of cultural events and exacerbated economic challenges, depriving artists and people working in the culture industry of their primary source of income. Such drastic conditions could lead to important professional decisions, including career changes. This study aimed to determine the factors that could influence career decisions among artistic professionals during a second pandemic lockdown period in Germany. To examine whether health concerns or financial struggles are more important in shaping artistic professionals’ decisions to change or stay in their profession, a vignette experiment was conducted in an online survey (n = 788) in the winter of 2020–2021. In the experiment’s 2*3-factorial randomised design, all respondents were asked to put themselves in the role of artists and make decisions about career changes under different income conditions or with different health prospects. The vignette experiment revealed that income losses related to career changes decreased the willingness to change careers, whereas health prospects (hypothetical differences in vaccine efficacy) did not affect the decisions. In addition, other variables were found to explain career decisions; female gender and signs of a depressive disorder were associated with greater willingness for career turnover, whereas a higher educational level and status of earning one’s livelihood in the culture industry were associated with a diminished tendency for career turnover. The latter impact factor was interpreted as a kind of “don´t give up effect” that is particularly observable among artistic professionals.
Discrepancies in corrected calcium versus ionised calcium in a geriatric population: an observational study
Authors: Suryapranata Alexandra P S P , Keijsers Carolina J P W , Kurstjens Steef , Van Strien Astrid M
Published: April 2024

Background

Calcium can be measured as ionised (Ca-ionised) or albumin-adjusted total calcium (Ca-albumin). Current clinical guidelines predominantly utilise Ca-albumin, despite Ca-ionised being the gold standard. Discrepancies can occur between these measurement modalities and can lead to clinical dilemmas. It remains unclear how large these discrepancies are in older patients. This study investigated the discrepancies between Ca-ionised and Ca-albumin in geriatric patients.

Methods

This is an observational study of all geriatric patients (n = 876) in the Jeroen Bosch Hospital (January 2018 and January 2021) in whom both Ca-ionised and Ca-albumin were measured. Misclassification of calcaemic state (i.e. low, normal or high) was calculated (percentages), the measure of agreement was described using Cohen’s Kappa and for the continuous data Pearson’s correlation coefficient was used. Relevant categories of age and renal function were considered for effect modification effects and studied by interaction terms in a regression model.

Results

In one-third of the measurements, there was a misclassification. Ca-albumin measurements failed to identify 28% of hypocalcaemia. In 3.5%, hypercalcemia based on Ca-albumin was not confirmed by Ca-ionised. The correlation coefficient between Ca-ionised and Ca-albumin was 0.743 (P = 0.01) and measure of agreement by Kappa was 0.213 (P < 0.001). In the oldest old (≥ 85 years) and patients with eGFR <30 ml/min/1.73 m2 ,the agreement by Kappa was lower, with values of 0.192 and 0.104, respectively.

Conclusion

There is a discrepancy between Ca-albumin and Ca-ionised in one-third of the geriatric patients, leading to clinical dilemmas. In the oldest old and patients with renal dysfunction, this problem is most pronounced.
Understanding the association between pain and delirium in older hospital inpatients: systematic review and meta-analysis
Authors: White Nicola , Bazo-Alvarez Juan Carlos , Koopmans Michel , West Emily , Sampson Elizabeth L
Published: April 2024

Objective

Delirium and pain are common in older adults admitted to hospital. The relationship between these is unclear, but clinically important. We aimed to systematically review the association between pain (at rest, movement, pain severity) and delirium in this population.

Methods

PubMed, EMBASE, CINAHL, PsycINFO, Cochrane and Web of Science were searched (January 1982–November 2022) for Medical Subject Heading terms and synonyms (‘Pain’, ‘Analgesic’, ‘Delirium’). Study eligibility: (1) validated pain measure as exposure, (2) validated delirium tool as an outcome; participant eligibility: (1) medical or surgical (planned/unplanned) inpatients, (2) admission length ≥ 48 h and (3) median cohort age over 65 years. Study quality was assessed with the Newcastle Ottawa Scale. We collected/calculated odds ratios (ORs) for categorical data and standard mean differences (SMDs) for continuous data and conducted multi-level random-intercepts meta-regression models. This review was prospectively registered with PROSPERO [18/5/2020] (CRD42020181346).

Results

Thirty studies were selected: 14 reported categorical data; 16 reported continuous data. Delirium prevalence ranged from 2.2 to 55%. In the multi-level analysis, pain at rest (OR 2.14; 95% confidence interval [CI] 1.39–3.30), movement (OR 1.30; 95% CI 0.66–2.56), pain categorised as ‘severe’ (OR 3.42; 95% CI 2.09–5.59) and increased pain severity when measured continuously (SMD 0.33; 95% CI 0.08–0.59) were associated with an increased delirium risk. There was substantial heterogeneity in both categorical (I2 = 0%–77%) and continuous analyses (I2 = 85%).

Conclusion

An increase in pain was associated with a higher risk of developing delirium. Adequate pain management with appropriate analgesia may reduce incidence and severity of delirium.
Challenges and patient outcomes in chronic subdural haematoma at the level of a regional care system A multi-centre, mixed-methods study from the East of England
Authors: Stubbs Daniel James , Khanna Sam , Davies Benjamin M , Vivian Mark E , Bashford Tom , Adatia Krishma , Chen Ping , Clarkson Peter John , McGlennan Catherine , Indurawage Lalani , Patel Martyn , Tyagunenko Rada , Burnstein Rowan , Menon David K , Hutchinson Peter J , Joannides Alexis ,   on behalf of the SENIOR-C team
Published: April 2024

Background

Chronic subdural haematoma (cSDH) is a common neurosurgical pathology affecting older patients with other health conditions. A significant proportion (up-to 90%) of referrals for surgery in neurosciences units (NSU) come from secondary care. However, the organisation of this care and the experience of patients repatriated to non-specialist centres are currently unclear.

Objectives

This study aimed to clarify patient outcome in non-specialist centres following NSU discharge for cSDH surgery and to understand key system challenges. The study was set within a representative neurosurgical care system in the east of England.

Design and methods

We performed a retrospective cohort analysis of patients referred for cSDH surgery. Alongside case record review, patient and staff experience were explored using surveys as well as an interactive c-design workshop. Challenges were identified from thematic analysis of survey responses and triangulated by focussed workshop discussions.

Results

Data on 381 patients referred for cSDH surgery from six centres was reviewed. One hundred and fifty-six (41%) patients were repatriated following surgery. Sixty-one (39%) of those repatriated suffered an inpatient complication (new infection, troponin rise or renal injury) following NSU discharge, with 58 requiring institutional discharge or new care. Surveys for staff (n = 42) and patients (n = 209) identified that resourcing, communication, and inter-hospital distance posed care challenges. This was corroborated through workshop discussions with stakeholders from two institutions.

Conclusions

A significant amount of perioperative care for cSDH is delivered outside of specialist centres. Future improvement initiatives must recognise the system-wide nature of delivery and the challenges such an arrangement presents.
Development and implementation of ambulatory care pharmacy services at an internal medicine clinic
Authors: Wells Casey , Warren Anne Carrington , Scott Mollie Ashe
Published: April 2024

Purpose

This report describes the step-by-step process that led to expansion of ambulatory care pharmacy services at a newly established internal medicine clinic within a patient-centered medical home in North Carolina.

Implementation of clinical pharmacist services at the clinic was led by a postgraduate year 2 (PGY2) pharmacy resident and guided by the 9 steps described in the book Building a Successful Ambulatory Care Practice: A Complete Guide for Pharmacists. After a needs assessment and review of the demographics and insurance status of the clinic’s target population, it was determined that pharmacist services would focus on quality measures including diabetes nephropathy screening, diabetes eye examination, blood glucose control in diabetes, discharge medication reconciliation, annual wellness visits, and medication adherence in diabetes, hypercholesterolemia, and hypertension. Clinic appointments were conducted under 3 models: a pharmacist-physician covisit model, a “floor model” of pharmacist consultation on drug information or medication management issues during medical resident sign-out sessions with supervising physicians (medical residents could also see patients along with the pharmacist at a covisit appointment), and a covisit model of stacked physician and pharmacist appointments. The pharmacist’s services were expanded from 2 half-day clinic sessions per week initially to 5 or 6 half-day clinic sessions by the end of the residency year.

Conclusion

By the fourth quarter of the first PGY2 residency year in which ambulatory care pharmacy services were provided in the clinic, the clinical and financial impact of those services justified the addition of a second full-time pharmacist to the clinic team.
Surveying biomedical relation extraction: a critical examination of current datasets and the proposal of a new resource
Authors: Huang Ming-Siang , Han Jen-Chieh , Lin Pei-Yen , You Yu-Ting , Tsai Richard Tzong-Han , Hsu Wen-Lian
Published: April 2024

Natural language processing (NLP) has become an essential technique in various fields, offering a wide range of possibilities for analyzing data and developing diverse NLP tasks. In the biomedical domain, understanding the complex relationships between compounds and proteins is critical, especially in the context of signal transduction and biochemical pathways. Among these relationships, protein–protein interactions (PPIs) are of particular interest, given their potential to trigger a variety of biological reactions. To improve the ability to predict PPI events, we propose the protein event detection dataset (PEDD), which comprises 6823 abstracts, 39 488 sentences and 182 937 gene pairs. Our PEDD dataset has been utilized in the AI CUP Biomedical Paper Analysis competition, where systems are challenged to predict 12 different relation types. In this paper, we review the state-of-the-art relation extraction research and provide an overview of the PEDD’s compilation process. Furthermore, we present the results of the PPI extraction competition and evaluate several language models’ performances on the PEDD. This paper’s outcomes will provide a valuable roadmap for future studies on protein event detection in NLP. By addressing this critical challenge, we hope to enable breakthroughs in drug discovery and enhance our understanding of the molecular mechanisms underlying various diseases.
GLIMMERS: glioma molecular markers exploration using long-read sequencing
Authors: Thongrattana Wichayapat , Arigul Tantip , Suktitipat Bhoom , Pithukpakorn Manop , Sathornsumetee Sith , Wongsurawat Thidathip , Jenjaroenpun Piroon
Published: April 2024

The revised WHO guidelines for classifying and grading brain tumors include several copy number variation (CNV) markers. The turnaround time for detecting CNVs and alterations throughout the entire genome is drastically reduced with the customized read incremental approach on the nanopore platform. However, this approach is challenging for non-bioinformaticians due to the need to use multiple software tools, extract CNV markers and interpret results, which creates barriers due to the time and specialized resources that are necessary. To address this problem and help clinicians classify and grade brain tumors, we developed GLIMMERS: glioma molecular markers exploration using long-read sequencing, an open-access tool that automatically analyzes nanopore-based CNV data and generates simplified reports.

Availability and implementation

GLIMMERS is available at https://gitlab.com/silol_public/glimmers under the terms of the MIT license.
NeoAgDT: optimization of personal neoantigen vaccine composition by digital twin simulation of a cancer cell population
Authors: Mösch Anja , Grazioli Filippo , Machart Pierre , Malone Brandon
Published: April 2024

Motivation

Neoantigen vaccines make use of tumor-specific mutations to enable the patient’s immune system to recognize and eliminate cancer. Selecting vaccine elements, however, is a complex task which needs to take into account not only the underlying antigen presentation pathway but also tumor heterogeneity.

Results

Here, we present NeoAgDT, a two-step approach consisting of: (i) simulating individual cancer cells to create a digital twin of the patient’s tumor cell population and (ii) optimizing the vaccine composition by integer linear programming based on this digital twin. NeoAgDT shows improved selection of experimentally validated neoantigens over ranking-based approaches in a study of seven patients.

Availability and implementation

The NeoAgDT code is published on Github: https://github.com/nec-research/neoagdt.
A data-adaptive methods in detecting exogenous methyltransferase accessible chromatin in human genome using nanopore sequencing
Authors: Tu Kailing , Li Xuemei , Zhang Qilin , Huang Wei , Xie Dan
Published: April 2024

Motivation

Identifying chromatin accessibility is one of the key steps in studying the regulation of eukaryotic genomes. The combination of exogenous methyltransferase and nanopore sequencing provides an strategy to identify open chromatin over long genomic ranges at the single-molecule scale. However, endogenous methylation, non-open-chromatin-specific exogenous methylation and base-calling errors limit the accuracy and hinders its application to complex genomes.

Results

We systematically evaluated the impact of these three influence factors, and developed a model-based computational method, methyltransferase accessible genome region finder (MAGNIFIER), to address the issues. By incorporating control data, MAGNIFIER attenuates the three influence factors with data-adaptive comparison strategy. We demonstrate that MAGNIFIER is not only sensitive to identify the open chromatin with much improved accuracy, but also able to detect the chromatin accessibility of repetitive regions that are missed by NGS-based methods. By incorporating long-read RNA-seq data, we revealed the association between the accessible Alu elements and non-classic gene isoforms.

Availability and implementation

Freely available on web at https://github.com/Goatofmountain/MAGNIFIER.
Sensitivity analysis for matched observational studies with continuous exposures and binary outcomes
Authors: Zhang Jeffrey , Small Dylan S , Heng Siyu
Published: April 2024

Matching is one of the most widely used study designs for adjusting for measured confounders in observational studies. However, unmeasured confounding may exist and cannot be removed by matching. Therefore, a sensitivity analysis is typically needed to assess a causal conclusion’s sensitivity to unmeasured confounding. Sensitivity analysis frameworks for binary exposures have been well established for various matching designs and are commonly used in various studies. However, unlike the binary exposure case, there still lacks valid and general sensitivity analysis methods for continuous exposures, except in some special cases such as pair matching. To fill this gap in the binary outcome case, we develop a sensitivity analysis framework for general matching designs with continuous exposures and binary outcomes. First, we use probabilistic lattice theory to show that our sensitivity analysis approach is finite population exact under Fisher’s sharp null. Second, we prove a novel design sensitivity formula as a powerful tool for asymptotically evaluating the performance of our sensitivity analysis approach. Third, to allow effect heterogeneity with binary outcomes, we introduce a framework for conducting asymptotically exact inference and sensitivity analysis on generalized attributable effects with binary outcomes via mixed-integer programming. Fourth, for the continuous outcome case, we show that conducting an asymptotically exact sensitivity analysis in matched observational studies when both the exposures and outcomes are continuous is generally NP-hard, except in some special cases such as pair matching. As a real data application, we apply our new methods to study the effect of early-life lead exposure on juvenile delinquency. An implementation of the methods in this work is available in the R package doseSens.
Genetic divergences provide evidence to accept a new Mediterranean genus Antalia (Apiaceae) and insights into allopatric divergence extended to the Pliocene
Authors: Doğru-Koca Aslı
Published: April 2024

Narrow endemism is the core of plant diversity in flora of the Mediterranean Basin, which is among the world’s 36 biodiversity hotspots. The Mediterranean genus Kundmannia (Careae, Apioideae) comprises just three species, K. sicula, K. anatolica, and K. syriaca. Notably, K. sicula has a wide distribution from the western Mediterranean to Greece, while K. anatolica and K. syriaca occur only in Turkey’s Taurus Mountains, which is a phylogeographical hotspot. Initially, the aim herein was to determine the phylogenetic placement of the genus Kundmannia based on DNA sequences, but it later developed to describing a new genus, Antalia gen. nov., and revealing historical events that acted as drivers in the genetic divergence between Kundmannia and Antalia. Both ribosomal and combined chloroplast multilocus sequences were used to unravel the phylogenetic topology. Toward this aim, morphological characteristics were examined. Based on this, Antalia differs from Kundmannia by its shorter bracteoles and petals, the colour of the petals, and smaller fruits. The phylogenetic results revealed that the genus Kundmannia is nested within the tribe Careae and is not monophyletic. Antalia, which is genetically separate from Kundmannia, is described as a new genus. Detailed morphological descriptions and identification keys are provided. Causes of the genetic disjunction between Antalia and Kundmannia were carefully considered in a time-calibrated phylogenetic framework. The Mediterranean Sea has acted as a relatively effective barrier between these genera since the Messinian salinity crisis. The unwinged mericarps seem to have facilitated the work of the barrier. Historical events during and after the Pliocene and allopatric vicariance seem to have been the most important drivers of evolution between Kundmannia and Antalia and within Antalia.
“An Australian beauty-lover based in Singapore”: negotiating Asian Australian identity in the beauty vlogosphere
Authors: Dejmanee Tisha
Published: April 2024

This article explores how the conventions and culture of beauty vlogging elucidate Asian Australian identity and politics. Drawing on a qualitative analysis of Asian Australian beauty vlogger Tina Yong’s vlogs, I explore how national, ethnic, and racial identities are negotiated through platform logics, commercial imperatives, and community participation. Yong’s vlogs offer tangible ways to narrate the mundane, everyday experiences of Asian Australian identity that are underrepresented in mainstream Australian media. At the same time, Yong’s self-representation is made legible through her engagements with the commercialized beauty vlogosphere and her transnational audience, which tend to reduce the potential for illuminating hybrid and culturally specific Asian Australian experiences, communities, and politics. While Yong’s vlogs generate productive dialogue on race/ethnicity and race-based affinity communities, platform and commercial logics hinder her representational capacity as an Asian Australian subject who is doubly marginalized within the global beauty vlogosphere.
A Multivariate analysis on evoked components of Chinese semantic congruity: an OP-MEG study with EEG
Authors: Wu Huanqi , Liang Xiaoyu , Wang Ruonan , Ma Yuyu , Gao Yang , Ning Xiaolin
Published: April 2024

The application of wearable magnetoencephalography using optically-pumped magnetometers has drawn extensive attention in the field of neuroscience. Electroencephalogram system can cover the whole head and reflect the overall activity of a large number of neurons. The efficacy of optically-pumped magnetometer in detecting event-related components can be validated through electroencephalogram results. Multivariate pattern analysis is capable of tracking the evolution of neurocognitive processes over time. In this paper, we adopted a classical Chinese semantic congruity paradigm and separately collected electroencephalogram and optically-pumped magnetometer signals. Then, we verified the consistency of optically-pumped magnetometer and electroencephalogram in detecting N400 using mutual information index. Multivariate pattern analysis revealed the difference in decoding performance of these two modalities, which can be further validated by dynamic/stable coding analysis on the temporal generalization matrix. The results from searchlight analysis provided a neural basis for this dissimilarity at the magnetoencephalography source level and the electroencephalogram sensor level. This study opens a new avenue for investigating the brain’s coding patterns using wearable magnetoencephalography and reveals the differences in sensitivity between the two modalities in reflecting neuron representation patterns.
Pituitary volumes in patients with adjustment disorder
Authors: Atmaca Murad , Bibar Alper , Tabara Muhammed Fatih , Koc Mustafa , Gurok Mehmet Gurkan , Korkmaz Sevda , Mermi Osman , Yildirim Hanefi
Published: April 2024

The pituitary gland plays an important role in the stress response mechanism. Given the direct link between adjustment disorder and stress, we hypothesized that there might be changes in the pituitary gland in these patients. The study comprised a patient group of 19 individuals with adjustment disorder according to the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition, and 18 healthy controls. The mean pituitary gland volumes of the patient group were not statistically significantly different from those of the healthy control group (80.81 ± 1.82 mm3 in patients with adjustment disorder vs. 81.10 ± 7.04 mm3 in healthy controls, with a statistically nonsignificant difference of P > 0.05). This finding is contrary to our previous findings in anxiety-related disorders. In this regard, adjustment disorder is not similar to anxiety-related disorders in terms of pituitary gland volumes. We should also clearly state that our study is a pioneering study and that studies with large samples are needed to support our findings. The limitations of our study can be attributed to the small sample size, the utilization of a cross-sectional design, and the inclusion of patients using psychotropic drugs.
Acute kidney injury and point-of-care ultrasound in liver cirrhosis: redefining hepatorenal syndrome
Authors: Banegas-Deras Eduardo Josué , Mazón-Ruiz Jaime , Romero-González Gregorio , Ruiz-Cobo Juan Carlos , Sanz-García Clara , Serrano-Soto Mara , Sánchez Emilio , Argaiz Eduardo R
Published: April 2024

Acute kidney injury (AKI) in patients with cirrhosis is a diagnostic challenge due to multiple and sometimes overlapping possible etiologies. Many times, diagnosis cannot be made based on case history, physical examination or laboratory data, especially when the nephrologist is faced with AKI with a hemodynamic basis, such as hepatorenal syndrome. In addition, the guidelines still include generalized recommendations regarding withdrawal of diuretics and plasma volume expansion with albumin for 48 h, which may be ineffective and counterproductive and may have iatrogenic effects, such as fluid overload and acute cardiogenic pulmonary edema. For this reason, the use of new tools, such as hemodynamic point-of-care ultrasound (PoCUS), allows us to phenotype volume status more accurately and ultimately guide medical treatment in a noninvasive, rapid and individualized manner.
Biological validation of faecal corticosterone metabolites as a non-invasive stress assessment in translocated California valley quail (Callipepla californica)
Authors: Currier Sarah A , Whitt Jeffrey G , Reyna Kelly S
Published: April 2024

US quail species are vulnerable to population declines as a result of climate change, habitat loss and habitat fragmentation, all of which can result in physiological stress. Additionally, population restoration techniques (PRTs), like translocations, also induce stress. Traditional assessments of avian stress hormone levels include capturing and handling birds to extract blood, methods that are inherently stressful and can compound stress analyses. However, the stress hormone corticosterone (CORT) is metabolized from the blood and excreted in faeces as faecal corticosterone metabolites (FCMs). FCMs have been used as a non-invasive measurement of stress hormone levels in a variety of species, but must be validated for each species. The objective of this study was to biologically validate the use of FCMs as a non-invasive measurement of CORT levels in California valley quail (Callipepla californica). Reference and treatment quail were acclimated for 3 weeks in an outdoor aviary. Subsequently, treatment quail were subjected to a simulated 48-h translocation, a common and stress hormone-inducing PRT. Faecal samples were collected every 4 h and processed using an enzyme immunoassay. Mean FCM concentrations of treatment quail (41.50 ± 16.13 ng/g) were higher than reference FCM concentrations (24.07 ± 10.4 ng/g). These results biologically validate the use of FCMs as a non-invasive method to assess CORT levels in California valley quail, demonstrate diurnal variation in quail CORT levels, and confirm that quail translocations are a stress-inducing PRT. Ultimately, this research validates a new non-invasive tool for stress response measurement to advance quail research, management and conservation.
Effectiveness and Persistency of Ustekinumab Treatment for Ulcerative Colitis: A Phoenix retrospective Cohort Study
Authors: Ando Katsuyoshi , Fujiya Mikihiro , Ueno Nobuhiro , Ito Takahiro , Maemoto Atsuo , Nasuno Masanao , Tanaka Hiroki , Sakurai Kensuke , Katsurada Takehiko , Orii Fumika , Ashida Toshifumi , Motoya Satoshi , Kazama Tomoe , Yokoyama Yoshihiro , Hirayama Daisuke , Nakase Hiroshi
Published: April 2024

Background

Real-world data regarding ustekinumab (UST) for ulcerative colitis (UC) particularly in biologics-naïve patients is currently limited. This study aimed to elucidate the real-world effectiveness and safety of UST for UC.

Methods

Overall, 150 patients with UC treated with UST from March 2020 to January 2023 were enrolled across 7 referral hospitals. To assess the clinical efficacy and persistence of UST, retrospective analyses were conducted from weeks 8 to 56. Predictive factors concerning the response and persistence of UST were examined through univariate and multivariate analyses.

Results

Of the 150 patients, 125 received UST for remission induction, including 36% biologics-naïve. The response and remission rates were 72.8% and 56.0% at week 8 and 73.2% and 63.4% at week 56, respectively. Biologics-naïve patients represented higher response and remission rates at week 8 (84.4% and 73.3%) than those with biologics exposure (66.2% and 46.2%). Patients with prior antitumor necrosis factor (anti-TNF) and vedolizumab (VDZ) exposure had relatively lower response and remission rates (34.5% and 24.1%, respectively). The 1-year cumulative persistence rate was 84.0%. Multivariate analysis revealed that the chronic continuous type and prior anti-TNF and VDZ exposure were negative predictive factors for week 8 responsiveness. Clinical response at week 8 was a predictor of 1-year persistence. Adverse event incidence remained notably low at 6.4%.

Conclusions

This study highlights the safety and effectiveness of UST as an induction and maintenance therapy for UC. Chronic continuous type and previous anti-TNF and VDZ exposure negatively contributed to short-term effectiveness, whereas short-term effectiveness provided good persistency.
CancerMHL: the database of integrating key DNA methylation, histone modifications and lncRNAs in cancer
Authors: Du Pengyu , Chen Yingli , Li Qianzhong , Gai Zhimin , Bai Hui , Zhang Luqiang , Liu Yuxian , Cao Yanni , Zhai Yuanyuan , Jin Wen
Published: April 2024

The discovery of key epigenetic modifications in cancer is of great significance for the study of disease biomarkers. Through the mining of epigenetic modification data relevant to cancer, some researches on epigenetic modifications are accumulating. In order to make it easier to integrate the effects of key epigenetic modifications on the related cancers, we established CancerMHL (http://www.positionprediction.cn/), which provide key DNA methylation, histone modifications and lncRNAs as well as the effect of these key epigenetic modifications on gene expression in several cancers. To facilitate data retrieval, CancerMHL offers flexible query options and filters, allowing users to access specific key epigenetic modifications according to their own needs. In addition, based on the epigenetic modification data, three online prediction tools had been offered in CancerMHL for users. CancerMHL will be a useful resource platform for further exploring novel and potential biomarkers and therapeutic targets in cancer.

Database URL: http://www.positionprediction.cn/
Efficacy and Safety of Etrasimod in Patients with Moderately to Severely Active Isolated Proctitis: Results From the Phase 3 ELEVATE UC Clinical Programme
Authors: Peyrin-Biroulet Laurent , Dubinsky Marla C , Sands Bruce E , Panés Julian , Schreiber Stefan , Reinisch Walter , Feagan Brian G , Danese Silvio , Yarur Andres J , D’Haens Geert R , Goetsch Martina , Wosik Karolina , Keating Michael , Lazin Krisztina , Wu Joseph , Modesto Irene , McDonnell Aoibhinn , Bartolome Lauren , Vermeire Séverine
Published: April 2024

Background and Aims

Pivotal trials in ulcerative colitis have historically excluded patients with isolated proctitis. Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis. This post hoc analysis assessed efficacy and safety of etrasimod 2 mg once daily in patients with isolated proctitis (centrally read) from the phase 3 ELEVATE UC 52 and ELEVATE UC 12 trials.

Methods

Patients, including those with isolated proctitis (<10 cm rectal involvement) who met all other inclusion criteria in ELEVATE UC 52 and ELEVATE UC 12, were randomised 2:1 to receive etrasimod or placebo. Primary, secondary and other identified efficacy endpoints and safety were assessed.

Results

We analysed data from 64 and 723 patients at Week 12 (both trials pooled), and 36 and 397 patients at Week 52 (ELEVATE UC 52 only) with isolated proctitis and more extensive colitis (≥10 cm rectal involvement), respectively. Patients with isolated proctitis receiving etrasimod demonstrated significant improvements versus placebo, including clinical remission rates at Weeks 12 (42.9% vs 13.6%) and 52 (44.4% vs 11.1%), endoscopic improvement (52.4% vs 22.7%) at Week 12 and bowel urgency numerical rating scale score at Week 12 (all p < 0.01). Generally similar trends were observed in patients with more extensive colitis. Safety was consistent across subgroups, with no new findings.

Conclusions

Etrasimod demonstrated significant improvements versus placebo in patients with isolated proctitis, and those with more extensive disease, in most efficacy endpoints at Week 12 and 52.

Clinicaltrials.gov: NCT03945188; NCT03996369
Concordant B and T Cell Heterogeneity Inferred from the multi-omic Landscape of Peripheral Blood Mononuclear Cells in a Crohn’s Disease Cohort
Authors: Brown Margaret , Dodd Anne , Shi Fang , Greenwood Emily , Nagpal Sini , Kolachala Vasantha L , Kugathasan Subra , Gibson Greg
Published: April 2024

Background and Aims

Crohn’s disease is characterised by inflammation in the gastrointestinal tract due to a combination of genetic, immune, and environmental factors. Transcriptomic and epigenomic profiling of intestinal tissue of Crohn’s disease patients have revealed valuable insights into pathology, but have not been conducted jointly on less invasive peripheral blood mononuclear cells [PBMCs]. Furthermore, the heterogeneous responses to treatments among individuals with Crohn’s disease imply hidden diversity of pathological mechanisms.

Methods

We employed single nucleus multi-omic analysis, integrating both snRNA-seq and snATAC-seq of PBMCs with a variety of open source, bioinformatics applications.

Results

Our findings reveal a diverse range of transcriptional signatures among individuals, highlighting the heterogeneity in PBMC profiles. Nevertheless, striking concordance between three heterogeneous groups was observed across B cells and T cells. Differential gene regulatory mechanisms partially explain these profiles, notably including a signature involving TGFß signalling in two individuals with Crohn’s disease. A mutation mapped to a transcription factor binding site within a differentially accessible peak associated with the expression of this pathway, with implications for a personalised approach to understanding disease pathology.

Conclusions

This study highlights how multi-omic analysis can reveal common regulatory mechanisms that underlie heterogeneity of PBMC profiles, one of which may be specific to inflammatory disease.
A case report of successful primary percutaneous coronary intervention to an occluded anomalous left main coronary artery arising from the right coronary sinus
Authors: Wong Christopher C Y , Pogatchnik Brian P , Clark Daniel E , Sharma Rahul P
Published: April 2024

Background

Anomalous aortic origin of a coronary artery from the opposite sinus is a rare congenital abnormality that may be encountered during primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI).

Case summary

A 65-year-old man presented with chest pain and signs of heart failure. Electrocardiogram demonstrated atrial fibrillation with ST elevation in the high lateral leads, and he was taken emergently to the cardiac catheterization laboratory for primary PCI. Coronary angiography identified the culprit to be an occluded anomalous left main coronary artery (LMCA) arising from the right coronary cusp, and primary PCI was successfully performed in the LMCA and the left anterior descending artery (LAD). Computed tomography angiography confirmed a benign retroaortic course of the anomalous LMCA with no additional high-risk features, as well as a new left atrial appendage thrombus. He subsequently developed deep venous thrombosis, acute pulmonary embolism, and acute kidney injury secondary to renal artery embolism with associated infarction. Workup for patent foramen ovale and thrombophilia were negative, and he was discharged in a stable condition. At 2-month follow-up, he was asymptomatic with no evidence of myocardial ischaemia on stress cardiac magnetic resonance imaging.

Discussion

We present the first reported case of an occluded anomalous LMCA arising from the right coronary sinus in a patient presenting with STEMI. Rapid recognition of this congenital anomaly and selection of an appropriate guide catheter were keys to achieving timely reperfusion and a good outcome in this case.
Cohort profile: the European Unified Registries On Heart Care Evaluation and Randomized Trials (EuroHeart)—acute coronary syndrome and percutaneous coronary intervention
Authors: Bhatty Asad , Wilkinson Chris , Batra Gorav , Alfredsson Joakim , Erlinge David , Ferreira Jorge , Guðmundsdóttir Ingibjörg J , Hrafnkelsdóttir þórdís Jóna , Ingimarsdóttir Inga Jóna , Irs Alar , Járai Zoltán , Jánosi András , Popescu Bogdan A , Santos Manuel , Vasko Peter , Vinereanu Dragos , Yap Jonathan , Maggioni Aldo P , Wallentin Lars , Casadei Barabara , Gale Chris P
Published: April 2024

Aims

The European Unified Registries On Heart Care Evaluation and Randomized Trials (EuroHeart) aims to improve the quality of care and clinical outcomes for patients with cardiovascular disease. The collaboration of acute coronary syndrome/percutaneous coronary intervention (ACS/PCI) registries is operational in seven vanguard European Society of Cardiology member countries.

Methods and results

Adults admitted to hospitals with ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) are included, and individual patient-level data collected and aligned according to the internationally agreed EuroHeart data standards for ACS/PCI. The registries provide up to 155 variables spanning patient demographics and clinical characteristics, in-hospital care, in-hospital outcomes, and discharge medications. After performing statistical analyses on patient data, participating countries transfer aggregated data to EuroHeart for international reporting. Between 1st January 2022 and 31st December 2022, 40 021 admissions (STEMI 46.7%, NSTEMI 53.3%) were recorded from 192 hospitals in the seven vanguard countries: Estonia, Hungary, Iceland, Portugal, Romania, Singapore, and Sweden. The mean age for the cohort was 67.9 (standard deviation 12.6) years, and it included 12 628 (31.6%) women.

Conclusion

The EuroHeart collaboration of ACS/PCI registries prospectively collects and analyses individual data for ACS and PCI at a national level, after which aggregated results are transferred to the EuroHeart Data Science Centre. The collaboration will expand to other countries and provide continuous insights into the provision of clinical care and outcomes for patients with ACS and undergoing PCI. It will serve as a unique international platform for quality improvement, observational research, and registry-based clinical trials.
Multilayer anisotropy along the Alaska-Aleutians Subduction zone
Authors: Birkey Andrew , Lynner Colton
Published: April 2024

Increasing evidence from seismic methods shows that anisotropy within subduction zones should consist of multiple layers. To test this, we calculate and model shear wave splitting across the Alaska-Aleutians Subduction Zone (AASZ), where previous studies have argued for separate layers of anisotropy in the subslab, slab and mantle wedge. We present an updated teleseismic splitting catalogue along the span of the AASZ, which has many broad-band seismometers recently upgraded to three components. Splitting observations are sparse in the Western Aleutians, and fast directions are oriented generally trench parallel. There are significantly more splitting measurements further east along the AASZ. We identify six regions in the Central and Eastern Aleutians, Alaskan Peninsula and Cook Inlet with a high density of splits suitable for multilayered anisotropy analyses. These regions were tested for multilayer anisotropy, and for five of the six regions we favour multiple layers over a single layer of anisotropy. We find that the optimal setup for our models is one with a dipping middle layer oriented parallel to palaeospreading. A prominent feature of our modelling is that fast directions above and below the dipping layer are generally oriented parallel to the strike of the slab. Additionally, we lay out a framework for robust and statistically reliable multilayer shear wave splitting modelling.