bluuebunny/crossref_metadata_2025 huggingface dataset:
Beyond conventional therapies: IVIG in treating severe fingolimod-rebound in a postpartum patient with MS
Authors: Tunç Abdulkadir , AKBAŞ Alihan Abdullah , Bozkurt Beyzanur , Oncel Samet
Published: July 2024

This case report details a female patient with multiple sclerosis in her 30s, who experienced a significant fingolimod rebound syndrome post partum, characterised by worsening neurological symptoms and severe demyelinating lesions. Traditional treatments, including steroids and plasmapheresis, were ineffective. However, the introduction of intravenous immunoglobulin (IVIG) led to remarkable improvement in her symptoms and disability status. This case highlights the complex immunological changes associated with fingolimod cessation and underscores IVIG’s potential as a valuable treatment in managing such rebounds.
Non-reporting of sport-related concussion symptoms: a cross-sectional study of community rugby league players in the UK
Authors: Tadmor Daniel Isaac , Chesson Lucy , Till Kevin , Phillips Gemma , Fairbank Laura , Brown James , Cross Matt , Gardner Andrew J , Johnston Rich D , Owen Cameron , Hendricks Sharief , Stokes Keith A , Jones Ben
Published: July 2024

Recognising and removing players with suspected sport-related concussions is crucial for community sports.

Objectives

Quantify rates and factors associated with non-reporting of concussion symptoms in community rugby league.

Methods

Overall, 484 community rugby league players aged ≥18 years and 965 parents of rugby league players aged <18 years completed an online survey, regarding concussion history, knowledge, prevalence and reasons for non-reporting of concussion, long-term implications and perceptions of concussion.

Results

Thirty-five percent of players aged ≥18 years and 22% of parents of players aged <18 years reported at least one concussion in the last two seasons. Forty-three percent of players aged ≥18 years and 5% of parents of players aged<18 years surveyed stated they did not report concussion-related symptoms sustained during 2020 and 2021 seasons. The two most common reasons for non-reporting of concussion symptoms were‘didn’t want to be ruled out of a match’and‘didn’t want to let down the team’. Players aged ≥18 years who received external coaching pressures around concussion were more likely to not report concussion symptoms. Over 40% of parents and players were concerned about the potential long-term implications. Ten percent of players aged ≥18 years and 7% of parents of players aged <18 years would encourage their family members/children to not play rugby league.

Conclusions

Non-reporting rates of suspected concussion symptoms in adult community players were twice as high as in professional rugby league, with similar reasons (wanting to play and not letting the team down). Engaging coaches to prioritise brain health and providing broader and appropriate education on concussion should be focused on, given the concerns reported by community players and parents.
Retention of survival swimming skills among SwimSafe graduates in rural communities of Bangladesh: Results from a cross-sectional study
Authors: Rahman Aminur , Ashraf Lamisa , Rahman AKM Fazlur , Bhuiyan Md. Al-Amin , Shafkat Hossain Md , Alam Zobaer , Talab Abu , Li Qingfeng , Bachani Abdulgafoor
Published: July 2024

Background

Drowning is the leading cause of death among children in rural Bangladesh. While survival swimming for children ages 6 years and above is recommended in low-income and middle-income countries, research into the long-term retention of survival swimming skills is absent.

Methods

The retention of four survival swimming skills, including swimming for 25 m, floating/treading for 30 s, reach rescue skills and throw rescue skills, was observed among those trained under the SwimSafe programme more than 10 years ago. Information about the practice of survival swimming skills among SwimSafe graduates and whether they recommended such lessons for others was also collected through surveys. A multistage sampling strategy was used. Descriptive statistics on the retention of survival swimming skills and other variables and ORs from logistic regression analysis were reported.

Results

A total of 3603 SwimSafe graduates were observed. The retention of swimming and floating/treading skills was 88.4% and 89.7%, respectively, and that of swimming and floating/treading skills combined was 84.2%. While 87.7% of the graduates retained reach rescue skills, the retention of throw rescue skills was lower (71.9%). Approximately 60.6% of the graduates retained all four survival swimming skills. The majority of the graduates (70.3%) rarely practised swimming following graduation. Overall, 61.7% of the graduates recommended other children to learn survival swimming skills.

Conclusion

The majority of the SwimSafe graduates retained swimming and floating/treading skills for over 10 years despite minimal practice. Retention of throw rescue skills was lower. Therefore, refresher training and awareness campaigns focused on survival swimming skills are recommended.
Homicides of American Indians/Alaska Natives in urban versus rural areas: United States National Violent Death Reporting System, 2003–2020
Authors: Corry Daniel T , Kollar Laura M Mercer , Betz Carter J , Fowler Katherine A , Kearns Megan C , Smith Sharon G , Satter Delight E
Published: July 2024

Background

Missing and Murdered Indigenous People is a historic and contemporary issue that has gained national attention. In 2021, homicide was the eighth leading cause of death among American Indian/Alaska Native (AIAN) persons aged between 1 and 54 years old, and homicide is the sixth leading cause of death among all AIAN males aged 1–54 years old.

Aim

These data will build knowledge around AIAN homicides and to identify circumstances that can aid in comprehensive Missing and Murdered Indigenous People prevention efforts.

Methods

AIAN homicide data came from Centers for Disease Control and Prevention’s National Violent Death Reporting System, a state/jurisdiction-based surveillance system that collects detailed information about characteristics and circumstances of violent deaths. We examined data from 2003 to 2020 (all available years) from participating states/jurisdictions. We also assessed sociodemographic characteristics of victims and suspects, incident characteristics and differences across dichotomised urban/rural status. The study was conducted in 2022.

Results

The National Violent Death Reporting System provided data on 2959 AIAN homicides from 2003 to 2020 (54.2% urban and 45.8% rural). Significant differences based on the two locations included type of weapon used, the location of the injury, race of the primary suspect, the victim’s relationship to the suspect and select circumstances precipitating the homicide including crimes precipitating the homicide and homicides stemming from intimate partner violence.

Outcomes

These findings provide crucial information to strengthen public health efforts for prevention.
Longitudinal relationships between early-life homelessness and school-aged asthma and wheezing
Authors: Keen Ryan , Kim Hannah Hayoung , Chen Jarvis T , Tiemeier Henning , Sandel Megan T , Denckla Christy , Slopen Natalie
Published: July 2024

Background

Homelessness is a disruptive life event with profound impacts on children’s health. It remains unclear, however, whether homelessness in early life has an enduring association with asthma and wheezing among school-aged children.

Objective

To test whether early-life homelessness is prospectively associated with asthma and wheezing during school-aged years.

Methods

We draw on data from 9242 children from the Avon Longitudinal Study of Parents and Children. Children were categorised as ‘ever’ or ‘never’ homeless based on maternal reports from the prenatal period through age 5 years. Children were assigned a binary indicator of asthma/wheezing based on maternal reports of asthma and wheezing at ages 6.8, 7.6 and 8.6 years. We used multilevel logistic regression models to test the association of interest in both bivariate analyses and models adjusted for a broad set of potential confounders. We conducted sensitivity analyses using generalised estimating equations and considering asthma and wheezing separately to test the robustness of the results.

Results

Between 12.1% and 14.3% of children had asthma or wheezing at ages 6.8, 7.6 and 8.6 years, and these conditions were more common among ever homeless participants. Ever-homeless children displayed higher odds of asthma or wheezing than never-homeless children (OR: 1.59, 95% CI 1.02 to 2.48) after adjustment for child, maternal and household risk factors. Sensitivity analyses yielded similar results.

Conclusion

Early-life homelessness is prospectively associated with asthma and wheezing among school-aged children and should be prioritised by interventions promoting healthy child development.
Application of reliability models for crash frequency analysis: implications for network-wide safety performance
Authors: Deljouyi Nasim , Patnala Phani Kumar , Mehran Babak , Regehr Jonathan D.
Published: July 2024

The present study demonstrated the potential applications of reliability models for crash analysis of a large highway network. Specifically, three major outcomes of reliability models were investigated: temporal distributions of crashes, reliability score, and expected number of crashes, using 20-year data (2001–2020) of crashes recorded on the Saskatchewan highway network. A series of reliability models were developed for crashes by crash severity, vehicle involvement, and highway type. First, the temporal distributions of crashes on each segment were fit to a statistical distribution. Second, the reliability scores were used to rank the high crash risk segments. Third, the mean expected crash frequency was used to develop network-wide safety performance functions for total and fatal crashes in urban and rural highway segments using Poisson–Tweedie (PTw) regression models. The developed PTw models showed that the presence of trucks in the traffic composition has a significant effect on crash frequency, especially for urban highway segments.
Spin-dependent conductance and magnetoresistance ratio in two magnetic-barrier structures
Authors: Zheng Xingrong , Li Feifei
Published: July 2024

An improved transfer matrix method is developed with modular matrices for rectangular electric and magnetic vector potentials, as well as the δ-function like potentials. As an example, the spin-dependent conductance in two-dimensional electron gas under modulation of two magnetic barriers are recalculated and compared with those illustrated in (Wang et al. Chin. Phys. B 19, 037301(2010)). The previous results are found inaccurate, their transfer matrix was derived for slowly varying magnetic vector potential, which is inappropriate for δ-function like Zeeman interaction potentials. Furthermore, the last transfer matrix of eq. (4) is also found incorrect, and the Zeeman interaction is wrongly expressed and mistakenly enhanced about (1/0.067 ≈ 15) times. Our improved method here is general and is demonstrated very fast forevaluating various spin-dependent transport properties in complex hybrid magnetic–electric structures.
Transmission error modeling and analysis of herringbone gear drive based on the measured manufacturing errors
Authors: Zhang Chu , Hu Yunbo , Dong Huimin , Wang Changqing
Published: July 2024

Transmission error (TE) is an important index affecting the positioning accuracy and dynamic performance of gear drive. An original discrete slice model for TE analysis of herringbone gear drive based on the measured manufacturing errors (MEs) is proposed, involving tooth surface error, cumulative pitch error, and alignment error of double helical surfaces. In the model, herringbone gears are discretized into a series of slices to deal with the three-dimensional contact problem. The measured cumulative pitch error and alignment error are described as the position error of slices, while the measured tooth surface error is constructed as the real surface shape by B-spline method. Thus, the measured MEs are converted into the contact gaps of slices. The compatibility and equilibrium equations under error and load conditions are derived from the kinematic geometry and elastic mechanics. Based on the discrete slice model, the relationship between measured ME and TE is established explicitly. The ME of herringbone gear drive is measured, the effects of measured ME on TE under no-load and load conditions were analyzed, and TE test of herringbone gears was carried out. The test results are consistent with the properties and values of simulations, which verifies the proposed model.
CASE REPORT: A SPORADIC BOVINE PAPULAR STOMATITIS VIRUS INFECTION IN DAIRY CALVES IN SOUTH TAIWAN
Authors: Hsu Huan-Yu , Chuang Yu-Ching , Hsu Wei-Yu , Huang Chih-Wei , Ke Guan-Ming
Published: July 2024

An outbreak of a disease with multiple erosive papules and ulcers on the lips, noses, and tongues of calves was reported in Taiwan in August 2023. Five of 11 2–4-month-old dairy calves were affected. Oral swabs, nasal swabs, and esophageal–pharyngeal fluid were collected and tested positive for bovine papular stomatitis virus (BPSV) via quantitative real-time polymerase chain reaction assay (qPCR) for all of the affected calves. All of the positive calves remained positive for BPSV after 1 month of the outbreak, and the viral loads of the affected calves did not decrease within this period. To determine the genetic characteristics of this outbreak strain, phylogenetic analysis was performed with the partial B2L sequence of BPSV. The results revealed that the virus strain was closely related to isolates from Japan, the United States, and France. This is the first report on an outbreak in this particular region since 1988 and the first molecular characterization of BPSV in Taiwan.
Deconstruction of the Franciscan Complex Central Terrane Mélange and re-evaluation of Franciscan mélanges and architecture of the northwestern San Francisco Bay Area, California, USA
Authors: Raymond Loren A.
Published: July 2024

Various mélange types occur within the Franciscan accretionary Complex of western California. The largest mélange body, called the Central Belt Mélange (or similar names) served earlier as the type example for the orogen-long, subduction channel model, yet in the northwestern San Francisco Bay Area the name does not accurately reflect the geology. The mélange designation was commonly applied where resistant exotic and native blocks of rock are scattered across a relatively smooth terrain. Detailed mapping shows that many blocks experienced post-accretion transport. Areally large rock masses previously designated as Central Belt Mélange consist of multiple units and less than 30% of the tectonostratigraphy is mélange. Weakly metamorphosed sandstone–mudrock broken to dismembered formational units and similarly deformed sandstone–mudrock submarine fan facies dominate the tectonostratigraphy. Subordinate mélanges of the northwestern San Francisco Bay Area are of tectonic or sedimentary origin. The sedimentary bodies represent submarine mass flow deposits. Tectonic mélanges mark Mesozoic subduction-zone faults or Cenozoic strike-slip faults. Discriminating between mélange types and their origins, and reconstructing tectonostratigraphic columns for major fault blocks, clarifies the primary accretionary complex architecture and reveals significant along-strike variations in the Franciscan subduction accretionary Complex.
A Segment Augmentation and Prediction Consistency Framework for Multi-label Unknown Intent Detection
Authors: Yang Jiacheng , Chen Miaoxin , Liu Cao , Dai Boqi , Zheng Hai-Tao , Wang Hui , Xie Rui , Kim Hong-Gee
Published: July 2024

Multi-label unknown intent detection is a challenging task where each utterance may contain not only multiple known but also unknown intents. To tackle this challenge, pioneers proposed to predict the intent number of the utterance first, then compare it with the results of known intent matching to decide whether the utterence contains unknown intent(s). Though they have made remarkable progress on this task, their methods still suffer from two important issues: (1) It is inadequate to extract multiple intents using only utterance encoding; (2) Optimizing two sub-tasks (intent number prediction and known intent matching) independently leads to inconsistent predictions. In this article, we propose to incorporate segment augmentation rather than only use utterance encoding to better detect multiple intents. We also design a prediction consistency module to bridge the gap between the two sub-tasks. Empirical results on MultiWOZ2.3 and MixSNIPS datasets show that our method achieves state-of-the-art performance and significantly improves the best baseline.
Enhancing Energy-Awareness in Deep Learning through Fine-Grained Energy Measurement
Authors: Rajput Saurabhsingh , Widmayer Tim , Shang Ziyuan , Kechagia Maria , Sarro Federica , Sharma Tushar
Published: July 2024

With the increasing usage, scale, and complexity of Deep Learning (
dl
) models, their rapidly growing energy consumption has become a critical concern. Promoting green development and energy awareness at different granularities is the need of the hour to limit carbon emissions of
dl
systems. However, the lack of standard and repeatable tools to accurately measure and optimize energy consumption at fine granularity (e.g., at the
api
level) hinders progress in this area.

This paper introduces
FECoM (Fine-grained Energy Consumption Meter)
, a framework for fine-grained
dl
energy consumption measurement.
FECoM
enables researchers and developers to profile
dl
api
s from energy perspective.
FECoM
addresses the challenges of fine-grained energy measurement using static instrumentation while considering factors such as computational load and temperature stability. We assess
FECoM
’s capability for fine-grained energy measurement for one of the most popular open-source
dl
frameworks, namely
TensorFlow
. Using
FECoM
, we also investigate the impact of parameter size and execution time on energy consumption, enriching our understanding of
TensorFlow
api
s’ energy profiles. Furthermore, we elaborate on the considerations and challenges while designing and implementing a fine-grained energy measurement tool. This work will facilitate further advances in
dl
energy measurement and the development of energy-aware practices for
dl
systems.
A NUMA-Aware Version of an Adaptive Self-Scheduling Loop Scheduler
Authors: Booth Joshua Dennis , Lane Phillip
Published: July 2024

Parallelizing code in a shared-memory environment is commonly done utilizing loop scheduling (LS) in a fork-join manner as in OpenMP. This manner of parallelization is popular due to its ease to code, but the choice of the LS method is important when the workload per iteration is highly variable. Currently, the shared-memory environment is evolving in high-performance computing as larger chiplet-based processors with high core counts and segmented L3 cache are introduced. These processors have a stronger non-uniform memory access (NUMA) effect than the previous generation of x86-64 processors. This work attempts to modify the adaptive self-scheduling loop scheduler known as
iCh
(
i
rregular
Ch
unk) for these NUMA environments while analyzing the impact of these systems on default OpenMP LS methods. In particular,
iCh
is as a default LS method for irregular applications (i.e., applications where the workload per iteration is highly variable) that guarantees “good” performance without tuning. The modified version, named
NiCh
, is demonstrated over multiple irregular applications to show the variation in performance. The work demonstrates that
NiCh
is able to better handle architectures with stronger NUMA effects, and particularly is better than
iCh
when the number of threads is greater than the number of cores. However,
NiCh
also comes with being less universally “good” than
iCh
and a set of parameters that are hardware dependent.
A Critical Evaluation of Network Approaches for Studying Species Interactions
Authors: Blüthgen Nico , Staab Michael
Published: July 2024

Ecological networks of species interactions are popular and provide powerful analytical tools for understanding variation in community structure and ecosystem functioning. However, network analyses and commonly used metrics such as nestedness and connectance have also attracted criticism. One major concern is that observed patterns are misinterpreted as niche properties such as specialization, whereas they may instead merely reflect variation in sampling, abundance, and/or diversity. As a result, studies potentially draw flawed conclusions about ecological function, stability, or coextinction risks. We highlight potential biases in analyzing and interpreting species-interaction networks and review the solutions available to overcome them, among which we particularly recommend the use of null models that account for species abundances. We show why considering variation across species and networks is important for understanding species interactions and their consequences. Network analyses can advance knowledge on the principles of species interactions but only when judiciously applied.
Up-Conversion Luminescence and Optical Temperature Sensing of Tb3+, Yb3+, Er3+ Doped (Gd, Y, Lu)2O2S Series Phosphors
Authors: Shao Di , Lu Liping , Sun Haiying , Bai Zhaohui
Published: July 2024

The phase analysis, luminous intensity, and luminescence lifetime of different doping concentrations of Tb3+ (1 mol %–11 mol %), Yb3+ (9 mol %–54 mol %), Er3+ (0.1 mol %–1.1 mol %) ions and different introduction concentrations of Y3+ (1 mol %–6 mol %) and Lu3+ (0.5 mol %–3 mol %) of Gd2O2S series phosphors were studied systematically. In addition, the energy transfer model of Tb3+-Yb3+-Er3+ was established by analyzing the changes of luminous intensity and luminescence lifetime of novel (Gd, Y, Lu)2O2S phosphors co-doped Tb3+, Yb3+ and Er3+ which were prepared by the coprecipitation-high temperature solid-state reaction method. The luminescence intensity ratio equations of the sample excited by 980 nm was obtained at 313–553 K. And the absolute sensitivities were 0.0033 (313 K). This work is of reference value to the study of the mechanism of up-conversion system.
Study on Two Inorganic Consumables in PMMA Electrochromic Devices Based on Work Function Differences
Authors: Liu Yuhang , Mengnan Ruan , Nie Shanshan , Lian Yi , Zhao Lei , Zhifeng Liu
Published: July 2024

In electrochromic devices, the dielectric layer is not only an electrode dielectric, but also can provide compensating ions for electrochromism. In this paper, three composite porous materials, PMMA/SiO2, PMMA/TiO2, and PMMA/SiO2/TiO2, were prepared and assembled using polymethyl cellulose (PMMA) as the polymer matrix, impurity medium (SiO2) and titanium dioxide (TiO2) inorganic polymers, and the effect of doping two inorganic porous materials on the electrochromic performance was studied. The optical recovery and cycle stability of electrochromic wear of the PMMA/SiO2/TiO2 composite structure are significantly improved compared with the loss of other ceramic structures. Cyclic voltammetry analysis shows that the lithium ion diffusion coefficient of the electrochromic device using the PMMA/SiO2/TiO2 composite ceramic structure is the largest, which is 2.5 × 10−14 cm2​ s−1 . The improvement of electrochromic performance is mainly due to the difference in work function between SiO2 and TiO2 on the figure of merit diagram, which leads to the directional movement of the resonator, accelerates the transmission rate of Li+ and further optimizes the electrochemical properties of the composite ceramic. This study provides an effective method to improve the performance of electrochromic devices.
Impaired microvascular insulin-dependent dilation in women with a history of gestational diabetes
Authors: Schwartz Kelsey S. , Hernandez Paola V. , Maurer Grace S. , Wetzel Elizabeth M. , Sun Mingyao , Jalal Diana I. , Stanhewicz Anna E.
Published: July 2024

Women who have gestational diabetes during pregnancy are at a greater risk for cardiovascular disease and type 2 diabetes in the decade following pregnancy. The mechanisms mediating this increased risk are unclear. Herein, we demonstrate that insulin-dependent microvascular responses are reduced in women who had gestational diabetes, despite the remission of glucose intolerance. This reduced microvascular sensitivity to insulin may contribute to increased cardiovascular disease and type 2 diabetes risk in these women.
Sex Differences in Suicide Attempts: A Cross‐Sectional Study in Patients with First‐Episode and Drug‐Naïve Major Depression Disorder
Authors: Zhu Yingzhao , Zhang Jun , Liu Junjun , Jia Fengnan , Li Zhe , Zhao Xueli , Li Chuanwei , Deng Hanxu , Zhou Yue , Xia Xingzhi , Yang Ruchang , Du Xiangdong , Zhang Xiangyang
Published: July 2024

Object. Sex differences in suicide attempts in first‐episode and drug‐naïve (FEDN) patients with major depression disorder remain unclear. This study is aimed to examine sex differences in the prevalence and clinical correlates of suicide attempts in FEDN patients with MDD. Materials and Methods. A cross‐sectional study was conducted on the FEDN patients with MDD, and 1,718 patients’ demography information and clinical data were collected. The Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and Positive and Negative Syndrome Scale (PANSS) were used to evaluate symptoms of depression, anxiety, and psychotic symptoms, respectively. Thyroid hormones, lipid profile, and fasting blood glucose (FBG) were measured. A history of suicide attempt was verified based on medical records and interviews with patients and their families. A 2 × 2 ANOVA was used to compare the clinical parameters of MDD patients in the suicide attempts subgroup and the sex subgroup, as well as whether there is an interaction between these two subgroups. Univariate analysis and multivariate binary logistic regression analyses were used to assess factors associated with suicide attempts. Results. There was no sex difference in rates of suicide attempt among FEND patients with MDD (male: 19.0% vs. female: 20.7%, χ2 = 0.663, p = 0.416). Compared to males and females without suicide attempts, those with suicide attempts had higher levels of LDL‐C and lower levels of HDL‐C. There was a statistically significant difference in the course of disease, educational level, and TG in the female group but not in the male group. In both male and female patients, Lg (TPOAb) and severe anxiety symptoms were found to be positively correlated with suicide attempts. In addition, in male patients, suicide attempts were positively correlated with TC and FBG, while negatively correlated with body mass index. In female patients, there was a positive correlation between the severity of depression and elevated systolic blood pressure with suicide attempts (all p < 0.05). Conclusion. Our study showed that there is no sex difference in the prevalence of suicide attempts in FEDN patients with MDD and there are differences in factors related to suicide attempts between male and female MDD patients.
Efficacy of Brucella Vaccines in Sheep: A Systematic Review and Meta‐Analysis
Authors: Li Lian-Min , Xiang Wen-Tao , Li Ting , Xiang Mei-Mei , Liu Fei , Li Jian-Ming
Published: July 2024

Background. Brucellosis is a major worldwide public health problem with economic and zoonotic implications. Despite the importance of vaccines in preventing brucellosis, no previous systematic evaluation of vaccination in sheep has been conducted. Materials and Methods. Articles were searched in databases such as PubMed, Science Direct, Cochrane, VIP, Wan Fang, and CNKI by screening the articles, and articles reporting Brucella vaccination in sheep were included in the study. Meta‐analysis was performed using random effects models to calculate pooled risk ratios for vaccines and to calculate vaccine effectiveness. Results. A total of 2,605 articles were retrieved, and 17 articles were obtained through screening for analysis. The effectiveness of vaccination was 65% (RR = 0.35, 95% CI: 0.27–0.36; VE = 65%), with the M5 vaccine being significantly more effective at 84% (RR = 0.1587, 95% CI: 0.0256–0.9858; VE = 84%) than the other vaccines, and intramuscular injection could be the best route of immunization. Rev.1 was indicated for female sheep, especially for pregnant ewes (RR = 0.2016, 95% CI: 0.1139–0.3569; VE = 80%), and for reduced abortions (RR = 0.0978, 95% CI: 0.0459–0.2085). Conclusion. This meta‐analysis was conducted to identify the relevant factors affecting vaccine efficacy. We recommend that sheep be inoculated intramuscularly with Rev.1, different inoculation protocols be adopted for sheep of different ages, and pregnant ewes be inoculated with Rev.1 to prevent abortion.
Chemerin Enhances Migration and Invasion of OC Cells via CMKLR1/RhoA/ROCK‐Mediated EMT
Authors: Sun Xiaojing , Guo Yi
Published: July 2024

Chemerin is a newly described adipokine with significant effects on obesity, metabolic disorders, and immune trafficking. Recently, chemerin has gained prominence for its potential roles in cancer and tumorigenesis with pro‐ or antitumor effects. To date, most referenced multifunctions of chemerin are attributed to the chemokine‐like receptor 1 (CMKLR1), distributing broadly in many tissues. This study investigates the in vitro roles of chemerin treatment on migration and invasion of ovarian carcinoma cells (OVCAR‐3 and SK‐OV‐3) and potential underlying mechanisms. Herein, exogenous chemerin treatment promotes growth and invasion of SK‐OV‐3 cells but has no significant effects on OVCAR‐3 cells. SK‐OV‐3 cells undergo morphological elongation characterized by epithelial‐to‐mesenchymal transition (EMT) and Ras homologous genome members A (RhoA)/Rho protein‐related curl spiral kinase‐1 (ROCK1) activation. Furthermore, chemerin‐enhanced invasion and EMT of SK‐OV‐3 cells are effectively blocked by C3 transferase (C3T) and Y27632 and RhoA and ROCK1 inhibitor, respectively. More importantly, RhoA/ROCK1‐EMT‐mediated SK‐OV‐3 cell invasion is orchestrated by CMKLR1 upregulation after chemerin treatment (50 ng/mL). The silencing of CMKLR1 significantly (P < 0.0001) reverses the chemerin‐enhanced invasion, EMT, and RhoA/ROCK1 activation of SK‐OV‐3 cells. Our study indicates that chemerin promotes invasion of OC cells via CMKLR1‐RhoA/ROCK1‐mediated EMT, offering a novel potential target for metastasis of OC.
Effectiveness Evaluation of a Graded Pharmaceutical Care Model in Women with Intrahepatic Cholestasis of Pregnancy: A Before‐After Study
Authors: Guo Xiaohui , Zhang Yuan , Shen Yike , Sheng Mengdi , Zhang Haixia , Mei Hongliang
Published: July 2024

Objective. Intrahepatic cholestasis of pregnancy (ICP) significantly impacts the maternal and fetal safety. Research on the role of clinical pharmacists in guiding drug therapy for this condition remains limited. This study aimed to evaluate the effectiveness of graded pharmaceutical care for women with intrahepatic cholestasis of pregnancy and to provide a theoretical foundation for clinical pharmacist services. Study Design. This study comprises a pre‐and‐post analysis of women with intrahepatic cholestasis of pregnancy (ICP) treated between December 2019 and June 2023 at a tertiary hospital in Jiangsu province. Each group consisted of 102 participants. The control group received standard treatment, while the guardianship group received graded pharmacological care provided by a clinical pharmacist. The effectiveness of pharmacological monitoring by clinical pharmacists was assessed by comparing and analyzing clinical outcome indicators, quality management indicators, safety indicators, and economic factors. Results. The guardianship group exhibited a noteworthy 12.8% reduction in combined adverse pregnancy outcome and more effective management of total prenatal bile acids compared to the control group (16.05 µmol/L vs. 22.85 µmol/L, P < 0.05). The guardianship group displayed superior rationalization of therapeutic drugs and medication duration (P < 0.05). The cost‐benefit analysis revealed a favorable economic impact concerning medication costs but did not indicate economic significance regarding total inpatient costs. Conclusion. The implementation of a graded pharmaceutical care model by a clinical pharmacist holds the potential to enhance outcomes for women experiencing intrahepatic cholestasis during pregnancy, mitigate adverse pregnancy results, optimize the rational utilization of therapeutic medications, and yield positive economic results.
Figure 6 from Epigenetic Induction of Cancer-Testis Antigens and Endogenous Retroviruses at Single-Cell Level Enhances Immune Recognition and Response in Glioma
Authors: Lai Thomas J. , Sun Lu , Li Kevin , Prins Terry J. , Treger Janet , Li Tie , Sun Matthew Z. , Nathanson David A. , Liau Linda M. , Lai Albert , Prins Robert M. , Everson Richard G.
Published: July 2024

DAC reactivates hERV expression in gliomaspheres. A, FPKM of ERV3 and HERVR family for primary gliomasphere cell lines (n = 7; *, P < 0.05; **, P < 0.01; two-tailed unpaired t test). B, Average fold change of mRNA expression of treated GS277 for ERV3 and ERVW1/Syncytin-1 as measured by qPCR (n = 3; *, P < 0.05; ***, P < 0.001; two-tailed unpaired t test). C, Heatmap and hierarchical clustering of hERV gene families. Scale represents z-score of hERV family FPKM normalized to housekeeping FPKM.
Figure 2 from Epigenetic Induction of Cancer-Testis Antigens and Endogenous Retroviruses at Single-Cell Level Enhances Immune Recognition and Response in Glioma
Authors: Lai Thomas J. , Sun Lu , Li Kevin , Prins Terry J. , Treger Janet , Li Tie , Sun Matthew Z. , Nathanson David A. , Liau Linda M. , Lai Albert , Prins Robert M. , Everson Richard G.
Published: July 2024

DAC immunesensitization promotes specific, robust, and polyfunctional NY-ESO-1 TCR CD8+ T-cell responses in primary GBM cell lines. A, Representative Bis-Seq-TA cloning lollipop diagram and (B) percent of methylated CpGs to total CpGs of first eight sites of analyzed CpG island in primary GS277 cells treated with DMSO or 0.5 µmol/L DAC for 12 days. C, Average fold change of mRNA expression of treated GS277 (n = 3; **, P < 0.01; two-tailed unpaired t test). D, Cytotoxic analysis of treated GS277 over a 40-hour period when co-incubated with NY-ESO-1 TCR-transduced effector T cells at E:T ratio of 1:1 and (E) at multiple E:T ratios (1:5, 1:2, 1:1, 2:1) at 20-hour (n = 3; *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001; multiple unpaired t tests). F, Uniform manifold approximation projection (UMAP) of CD8+ T cells transduced with NY-ESO-1 TCR CD8 or untransduced control CD8 (CTR) from four stimulated groups: NY-ESO-1 CD8+ alone (n = 1665 CD8+ cells), NY-ESO-1 CD8+ stimulated with DBTRG-05 (n = 1902 CD8+ cells), NY-ESO-1 CD8+ stimulated with DBTRG-05 + DAC (n = 284 CD8+ cells), CTR CD8 stimulated with DBTRG-05 + DAC (n = 807 CD8+ cells). G and H, PSI defined as the percentage of polyfunctional cells, multiplied by MFI of the proteins secreted by the polyfunctional cells for stimulated CD8+ at the single-cell resolution across DBTRG-05 co-cultures.
Data from Epigenetic Induction of Cancer-Testis Antigens and Endogenous Retroviruses at Single-Cell Level Enhances Immune Recognition and Response in Glioma
Authors: Lai Thomas J. , Sun Lu , Li Kevin , Prins Terry J. , Treger Janet , Li Tie , Sun Matthew Z. , Nathanson David A. , Liau Linda M. , Lai Albert , Prins Robert M. , Everson Richard G.
Published: July 2024

Abstract
Glioblastoma (GBM) is the most common malignant primary brain tumor and remains incurable. Previous work has shown that systemic administration of Decitabine (DAC) induces sufficient expression of cancer-testis antigens (CTA) in GBM for targeting by adoptive T-cell therapy in vivo. However, the mechanisms by which DAC enhances immunogenicity in GBM remain to be elucidated. Using New York esophageal squamous cell carcinoma 1 (NY-ESO-1) as a representative inducible CTA, we demonstrate in patient tissue, immortalized glioma cells, and primary patient-derived gliomaspheres that basal CTA expression is restricted by promoter hypermethylation in gliomas. DAC treatment of glioma cells specifically inhibits DNA methylation silencing to render NY-ESO-1 and other CTA into inducible tumor antigens at single-cell resolution. Functionally, NY-ESO-1 T-cell receptor–engineered effector cell targeting of DAC-induced antigen in primary glioma cells promotes specific and polyfunctional T-cell cytokine profiles. In addition to induction of CTA, DAC concomitantly reactivates tumor-intrinsic human endogenous retroviruses, interferon response signatures, and MHC-I. Overall, we demonstrate that DAC induces targetable tumor antigen and enhances T-cell functionality against GBM, ultimately contributing to the improvement of targeted immune therapies in glioma.
Significance:
This study dissects the tumor-intrinsic epigenetic and transcriptional mechanisms underlying enhanced T-cell functionality targeting decitabine-induced cancer-testis antigens in glioma. Our findings demonstrate concomitant induction of tumor antigens, reactivation of human endogenous retroviruses, and stimulation of interferon signaling as a mechanistic rationale to epigenetically prime human gliomas to immunotherapeutic targeting.
Tumoral Interferon Beta Induces an Immune-Stimulatory Phenotype in Tumor-Associated Macrophages in Melanoma Brain Metastases
Authors: Gellert Julia , Agardy Dennis A. , Kumar Swaminathan , Kourtesakis Alexandros , Boschert Tamara , Jähne Kristine , Breckwoldt Michael O. , Bunse Lukas , Wick Wolfgang , Davies Michael A. , Platten Michael , Bunse Theresa
Published: July 2024

Type I interferons (IFN) are immune-stimulatory cytokines involved in antiviral and antitumor immune responses. They enhance the efficacy of immunogenic anticancer therapies such as radiotherapy by activating both innate and adaptive immune cells. Macrophages are one of the most abundant innate immune cells in the immune microenvironment of melanoma brain metastases (MBM) and can exert potent immune-suppressive functions. Here, we investigate the potential of tumoral type I IFNs to repolarize tumor-associated macrophages (TAM) in two murine MBM models and assess the effects of radiotherapy-induced type I IFN on TAMs in a transcriptomic MBM patient dataset. In mice, we describe a proinflammatory M1-like TAM phenotype induced by tumoral IFNβ and identify a myeloid type I IFN-response signature associated with a high M1/M2-like TAM ratio. Following irradiation, patients with MBM displaying a myeloid type I IFN-response signature showed increased overall survival, providing evidence that tumoral IFNβ supports an effective antitumor immune response by re-educating immune-regulatory TAM. These findings uncover type I IFN–inducing therapies as a potential macrophage-targeting therapeutic approach and provide a rationale for combining radiotherapy with concomitant immunotherapy to improve treatment response in patients with MBM.

Significance:

Our study shows that re-education of tumor-associated macrophages by tumoral IFNβ translates into improved clinical outcome in patients with melanoma brain metastases, providing pathomechanistic insights into synergistic type I interferon–inducing therapies with immunotherapies and warranting investigation of IFNβ as a predictive biomarker for combined radioimmunotherapy.
Another Round: Influence of Alcohol-Related Conditions and Other Drug Use-Related Disorders in Emergency Department Frequent Use – A Single-Site Matched Case-Control Study in Spain
Authors: Oliveras Clara , Bruguera Pol , Cordero Torres Imanol , Millán Hernández Andrea , Pons Maria Teresa , Guzmán Cortez Pablo Rodrigo , Gómez-Ramiro Marta , Vázquez Vallejo Mireia , Salgado Emilio , Asenjo Romero Maria , Vieta Eduard , Gual Antoni , López-Pelayo Hugo , Balcells-Oliveró Mercè
Published: July 2024

Introduction: Patients who make 5 or more visits per year to hospital emergency departments (EDs) are usually considered ED frequent users (FUs). This study aims to better characterize the influence of alcohol and other drug use-related disorders in this phenomenon in a European Mediterranean country with public, universal, tax-financed healthcare system. Methods: Matched case-control study. Cases were adults between 18 and 65 years old who consulted 5 or more times the ED of a tertiary hospital in Spain between December 2018 and November 2019. Each case was assigned a control of the same age and gender, who appeared to the ED on the same day, but who made 4 visits or less to the service during the study period. The electronic record of the first ED visit during this period was used to extract the variables of interest: emergency care received, clinical and social characteristics. Predictors of frequent ED use were identified with conditional logistic regression. Results: 609 case-control pairs (total n = 1,218) were selected. History of alcohol-related conditions (adjusted odds ratio [AOR] = 1.82 [95% CI: 1.26–2.64] p = 0.001) and also other drug use-related disorders (AOR = 1.50 [95% CI: 1.11–2.03] p = 0.009) significantly increased the probability of frequent use of emergency services. Discussion/Conclusion: Alcohol-related conditions and other drug use-related disorders must be evaluated in all ED FUs. Specific action protocols to concurrently address repeated attendance and addictions in the emergency room could be a good tool to reduce frequent ED use.
Allergy in Young Adults Associates with Elevated Fractional Exhaled Nitric Oxide Levels and IgE-Verified Parental Allergy but Is Confounded by Self-Reported Symptoms
Authors: Hellberg Ulrika , Sverremark-Ekström Eva , Nopp Anna , Nilsson Caroline
Published: July 2024

Introduction: Knowledge of IgE-verified allergy in young adults is limited as most studies are based on self-reported data. Allergic heredity is important in allergy development in early life, but less is known about the hereditary component later in life. The aim was to investigate IgE-verified and self-reported allergy and asthma at 20 years of age in association to parental allergy and environmental factors. Methods: In total, 281 individuals born into the cohort of well-characterized parents regarding allergic disease were followed to 20 years of age. The participants were categorized by parental allergy and examined regarding allergic diseases (IgE sensitization and allergic symptoms) at 2, 5, 10, and 20 years of age. FeNO was measured at 10 and 20 years. Results: In total, 45% of the study participants were allergic, with twice as many self-reported cases at age 20. Rhinitis was key to distinguishing confirmed allergy from self-reported. Having two allergic parents and increased FeNO were associated with an increased prevalence of allergic disease at 20 years. From a longitudinal perspective, rhinitis increased from childhood to young adulthood, in all heredity groups. Conclusion: In this longitudinal study, we have shown that two allergic parents as well as increased FeNO levels seem to be of importance for being allergic at 20 years old. Self-reported allergy was overreported – a result that should be considered in future survey-based reports on allergic diseases.
Human Proenkephalin A 119-159 (penKid) in Extracorporeal Therapies: Ex vivo Sieving Coefficient, Diffusive Clearance, and Hemoadsorption Kinetics
Authors: Lorenzin Anna , de Cal Massimo , Perin Natascha , Morisi Niccolò , Brendolan Alessandra , Lentini Paolo , Zanella Monica , Ronco Claudio
Published: July 2024

Introduction: Enkephalins, endogenous opioid peptides, are involved in the regulation of renal function. One derived molecule, proenkephalin A, also known as penKid, has been demonstrated to be a reliable biomarker for kidney function and its plasma concentration correlates with measured glomerular filtration rate. penKid is used for prediction and diagnosis of AKI and need of renal replacement therapy (RRT). penKid has also been used to predict the successful weaning from RRT in patients with AKI. Whether the concentration of penKid is affected or not by RRT is a controversial point and there are no studies describing the kinetics of the molecule in such conditions. The low molecular weight (4.5 kDa) would imply free removal by the glomerulus and the dialysis membranes. During RRT, this reduction could not be detected in clinical practice due to the complex kinetics involving either low dialytic clearance or increased production in response to impaired kidney function. The aim of this study was to determine the sieving coefficient and the diffusive clearance of the penKid molecule in conditions of in vitro continuous veno-venous hemofiltration (CVVH) and continuous veno-venous hemodialysis (CVVHD), respectively, and also the penKid removal ratio in conditions of in vitro hemoadsorption (HA) using a synthetic microporous resin. Methods: Blood spiked with a lyophilized penKid peptide solved in 20 mm dipotassium phosphate and 6 mm disodium EDTA [pH 8] to reach target concentrations is used as testing solution. In each experiment, the blood batch was adjusted at a volume of 1,000 mL, maintained at 37°, and continuously stirred. Samples were collected from blood, ultrafiltrate, and spent dialysate at different times during the experiments. Sieving, clearance, and removal ratio were calculated. Results: Significant removal of penKid was observed in CVVH (sieving 1.04 ± 0.27), in CVVHD (clearance 23.08 ± 0.89), and in HA (removal ratio 76.1 ± 1% after 120 min). Conclusion: penKid is effectively removed by extracorporeal therapies. In presence of anuria, penKid generation kinetics can be calculated based on extracorporeal removal and volume variation. In steady state conditions, declining values may be the result of an initial renal function recovery and may suggest discontinuation and successful liberation from RRT.
Infective Endocarditis in Patients Receiving Hemodialysis: A Current Review
Authors: Ding UZhe , Ooi LiJin , Wu Henry H.L. , Chinnadurai Rajkumar
Published: July 2024

Background: Cardiovascular and infective complications are commonly observed in patients receiving hemodialysis (HD) with cardiovascular events and infection-related complications being the first and second leading causes of death. Infective endocarditis (IE) is characterized by inflammation of the endocardium caused by infection, typically affecting the cardiac valves and can be in acute, subacute, or chronic forms. It is a serious complication within the HD population due to their predisposition for both infection and valvular damage. Considering the frailty and burden of comorbidities in those receiving HD, management of IE in the HD population is very challenging. There has been continuous discussion and debate on optimizing the diagnostic and treatment approach of IE in this patient group to improve their clinical outcomes. Currently, reported outcomes are relatively poor and there are updates from numerous guidelines relating to advances in IE management. Summary: In this review, we will evaluate the evidence in relation to the epidemiology of HD-associated IE and discuss the important risk factors of IE in patients requiring dialysis. We will also evaluate the current recommendations regarding diagnosis and treatment for suspected or confirmed IE cases amongst HD patients and present the updated data regarding clinical outcomes relating to HD-associated IE. Key Messages: The incidence of IE in HD patients is expected to increase going forward as HD becomes more easily accessible alongside an emerging uptake of home HD. A more thorough insight into this topic is required to improve clinical practice relating to IE prevention and management in the HD population, given relatively poor clinical outcomes.