bluuebunny/crossref_metadata_2025_split huggingface dataset:
Positive Impact of an Educational Brochure on Follow-Up for a Formal Hearing Evaluation
Authors: Wallhagen Margaret I , Strawbridge William J 
Published: March 2024

Abstract

Background and Objectives
Half of older persons experience serious hearing loss, yet it remains under-assessed in primary care clinics. Providers note time constraints as barriers and patients often minimize or deny their hearing loss. We tested the effectiveness of a simple hearing screen in primary care settings and whether including a brochure describing hearing loss, its consequences, and treatment would increase referrals for formal audiometric assessments.

Research Design and Methods
We designed a longitudinal effectiveness study assessing three interventions: Screening alone; Screening plus a brochure handed to the person testing positive; and Screening plus the brochure with a brief review. The screening was accomplished by intake personnel. The results of a positive screen were given to the primary care practitioner. The approach was designed to enable its use across a range of primary care settings. Follow-ups occurred at 4 and 8 months.

Results
A total of 111 older adults attending 7 primary care clinics screened positive for having possible hearing loss by intake personnel. A total of 46 received the educational brochure. Physicians discussed test results with two-thirds yet recommended further testing for only half of the participants. Physician recommendations were strongly motivating (OR = 9.12, 95% CI: 3.54–23.52) and those receiving the brochure were still more likely to seek further testing (OR = 2.61, 95% CI: 1.07–6.36) even when physician recommendations were controlled. Additionally, when combined, the 2 options were strongly motivating: all participants receiving both a referral and a brochure sought further testing.

Discussion and Implications
A simple screen and educational brochure on hearing loss improved follow-up for a formal hearing evaluation which may improve hearing health care and minimize negative outcomes. The study also identified barriers to implementation, including how to motivate practitioners and assist intake personnel in integrating hearing screening into their routine intake procedures, supporting further research.
Clinical Trials Registration Number: NCT0203713 9
Functional analysis of cell lines derived from SMAD3-related Loeys-Dietz syndrome patients provides insights into genotype-phenotype relation
Authors: de Wagenaar Nathalie P , van den Bersselaar Lisa M , Odijk Hanny J H M , Stefens Sanne J M , Reinhardt Dieter P , Roos-Hesselink Jolien W , Kanaar Roland , Verhagen Judith M A , Brüggenwirth Hennie T , van de Laar Ingrid M B H , van der Pluijm Ingrid , Essers Jeroen 
Published: March 2024

AbstractRationalePathogenic (P)/likely pathogenic (LP) SMAD3 variants cause Loeys-Dietz syndrome type 3 (LDS3), which is characterized by arterial aneurysms, dissections and tortuosity throughout the vascular system combined with osteoarthritis.ObjectivesInvestigate the impact of P/LP SMAD3 variants with functional tests on patient-derived fibroblasts and vascular smooth muscle cells (VSMCs), to optimize interpretation of SMAD3 variants.MethodsA retrospective analysis on clinical data from individuals with a P/LP SMAD3 variant and functional analyses on SMAD3 patient-derived VSMCs and SMAD3 patient-derived fibroblasts, differentiated into myofibroblasts.ResultsIndividuals with dominant negative (DN) SMAD3 variant in the MH2 domain exhibited more major events (66.7% vs. 44.0%, P = 0.054), occurring at a younger age compared to those with haploinsufficient (HI) variants. The age at first major event was 35.0 years [IQR 29.0–47.0] in individuals with DN variants in MH2, compared to 46.0 years [IQR 40.0–54.0] in those with HI variants (P = 0.065). Fibroblasts carrying DN SMAD3 variants displayed reduced differentiation potential, contrasting with increased differentiation potential in HI SMAD3 variant fibroblasts. HI SMAD3 variant VSMCs showed elevated SMA expression and altered expression of alternative MYH11 isoforms. DN SMAD3 variant myofibroblasts demonstrated reduced extracellular matrix formation compared to control cell lines.ConclusionDistinguishing between P/LP HI and DN SMAD3 variants can be achieved by assessing differentiation potential, and SMA and MYH11 expression. The differences between DN and HI SMAD3 variant fibroblasts and VSMCs potentially contribute to the differences in disease manifestation. Notably, myofibroblast differentiation seems a suitable alternative in vitro test system compared to VSMCs.
Study of prognostic splicing factors in cancer using machine learning approaches
Authors: Yang Mengyuan , Liu Jiajia , Kim Pora , Zhou Xiaobo 
Published: March 2024

Abstract
Splicing factors (SFs) are the major RNA-binding proteins (RBPs) and key molecules that regulate the splicing of mRNA molecules through binding to mRNAs. The expression of splicing factors is frequently deregulated in different cancer types, causing the generation of oncogenic proteins involved in cancer hallmarks. In this study, we investigated the genes that encode RNA-binding proteins and identified potential splicing factors that contribute to the aberrant splicing applying a random forest classification model. The result suggested 56 splicing factors were related to the prognosis of 13 cancers, two SF complexes in liver hepatocellular carcinoma, and one SF complex in esophageal carcinoma. Further systematic bioinformatics studies on these cancer prognostic splicing factors and their related alternative splicing events revealed the potential regulations in a cancer-specific manner. Our analysis found high ILF2-ILF3 expression correlates with poor prognosis in LIHC through alternative splicing. These findings emphasize the importance of SFs as potential indicators for prognosis or targets for therapeutic interventions. Their roles in cancer exhibit complexity and are contingent upon the specific context in which they operate. This recognition further underscores the need for a comprehensive understanding and exploration of the role of SFs in different types of cancer, paving the way for their potential utilization in prognostic assessments and the development of targeted therapies.
Characterization of the Neurochemical and Behavioral Effects of the Phenethylamine 2-Cl-4,5-MDMA in Adolescent and Adult Male Rats
Authors: Piras Gessica , Cadoni Cristina , Caria Francesca , Pintori Nicholas , Spano Enrica , Vanejevs Maksims , Ture Anastasija , Tocco Graziella , Simola Nicola , De Luca Maria Antonietta 
Published: March 2024

Abstract

Background
The proliferation of novel psychoactive substances (NPS) in the drug market raises concerns about uncertainty on their pharmacological profile and the health hazard linked to their use. Within the category of synthetic stimulant NPS, the phenethylamine 2-Cl-4,5-methylenedioxymethamphetamine (2-Cl-4,5-MDMA) has been linked to severe intoxication requiring hospitalization. Thereby, the characterization of its pharmacological profile is urgently warranted.

Methods
By in vivo brain microdialysis in adolescent and adult male rats we investigated the effects of 2-Cl-4,5-MDMA on dopamine (DA) and serotonin (5-HT) neurotransmission in two brain areas critical for the motivational and rewarding properties of drugs, the nucleus accumbens (NAc) shell and the medial prefrontal cortex (mPFC). Moreover, we evaluated the locomotor and stereotyped activity induced by 2-Cl-4,5-MDMA and the emission of 50-kHz ultrasonic vocalizations (USVs) to characterize its affective properties.

Results
2-Cl-4,5-MDMA increased dialysate DA and 5-HT in a dose-, brain area-, and age-dependent manner. Notably, 2-Cl-4,5-MDMA more markedly increased dialysate DA in the NAc shell and mPFC of adult than adolescent rats, while the opposite was observed on dialysate 5-HT in the NAc shell, with adolescent rats being more responsive. Furthermore, 2-Cl-4,5-MDMA stimulated locomotion and stereotyped activity in both adolescent and adult rats, although to a greater extent in adolescents. Finally, 2-Cl-4,5-MDMA did not stimulate the emission of 50-kHz USVs.

Conclusions
This is the first pharmacological characterization of 2-Cl-4,5-MDMA demonstrating that its neurochemical and behavioral effects may differ between adolescence and adulthood. These preclinical data could help understanding the central effects of 2-Cl-4,5-MDMA by increasing awareness on possible health damage in users.
A Phase 1, Double-Blinded, Placebo-Controlled Clinical Trial to Evaluate the Safety and Immunogenicity of HEV-239 (Hecolin) Vaccine in Healthy US Adults
Authors: Kao Carol M , Rostad Christina A , Nolan Lauren E , Peters Etza , Kleinhenz Jennifer , Sherman Jacob D , Tippett Ashley , Shih J Wai Kuo , Yildirim Inci , Agbakoba Vivien , Beresnev Tatiana , Ballou Cassandra , Kamidani Satoshi , Karmali Vinit , Natrajan Muktha , Scherer Erin M , Rouphael Nadine , Anderson Evan J 
Published: March 2024

Abstract

Background
Establishing the safety and immunogenicity of a hepatitis E virus vaccine in multiple populations could facilitate broader access and prevent maternal and infant mortality.

Methods
We conducted a phase 1, randomized, double-blinded, placebo-controlled (4:1 vaccine to placebo) trial of 30 µg HEV-239 (Hecolin, Xiamen Innovax Biotech Company Limited, China) administered intramuscularly in healthy US adults aged 18–45 years. Participants were vaccinated on days 1, 29, and 180. Participants reported solicited local and systemic reactions for 7 days following vaccination and were followed through 12 months after enrollment for safety and immunogenicity (IgG, IgM).

Results
Solicited local and systemic reactions between treatment and placebo group were similar and overall mild. No participants experienced serious adverse events related to HEV-239. All participants receiving HEV-239 seroconverted at 1 month following the first dose and remained seropositive throughout the study. HEV-239 elicited a robust hepatitis E IgG response that peaked 1 month following the second dose (geometric mean concentration [GMC], 6.16; 95% confidence interval [CI], 4.40–8.63), was boosted with the third dose (GMC, 11.50; 95% CI, 7.90–16.75) and persisted through 6 months.

Conclusions
HEV-239 is safe and elicits a durable immune response through at least 6 months after the third dose in healthy US adults.

Clinical Trials Registration
NCT03827395.
Trends of pre-treatment drug resistance in antiretroviral-naïve people with HIV-1 in the era of second-generation integrase strand-transfer inhibitors in Taiwan
Authors: Chen Guan-Jhou , Cheng Chien-Yu , Yang Chia-Jui , Lee Nan-Yao , Tang Hung-Jen , Huang Sung-Hsi , Huang Miao-Hui , Liou Bo-Huang , Lee Yi-Chien , Lin Chi-Ying , Hung Tung-Che , Lin Shih-Ping , Sun Hsin-Yun , Chang Sui-Yuan , Hung Chien-Ching ,   Taiwan HIV Study Group, Hung Chien-Ching , Chang Sui-Yuan , Sun Hsin-Yun , Huang Yu-Shan , Lin Kuan-Yin , Chen Guan-Jhou , Wu Pei-Ying , Chen Ling-Ya , Chang Hsi-Yen , Liu Wen-Chun , Su Yi-Ching , Wang Ning-Chi , Lin Te-Yu , Yang Chia-Jui , Tsai Mao-Song , Lee Mei-Hui , Lee Yi-Chien , Cheng Shu-Hsing , Cheng Chien-Yu , Liou Bo-Huang , Huang Sung-Hsi , Huang Yi-Chia , Peng An-Ting , Lee Yuan-Ti , Lee Yu-Lin , Lin Chia-Chun , Lin Shih-Ping , Hsieh Chia-Yin , Wang Hsiu-Wen , Ho Mao-Wang , Liu Chun-Eng , Hii Ing-Moi , Lin Chi-Ying , Tang Hung-Jen , Lee Nan-Yao , Tsai Chin-Shiang , Hung Tung-Che , Chen Yen-Hsu , Lu Po-Liang , Lee Chun-Yuan , Chen Tun-Chieh , Tsai Hung-Chin , Lin Hsi-Hsun , Lee Chen-Hsiang 
Published: March 2024

Abstract

Background
Monitoring the trends of pre-treatment drug resistance (PDR) and resistance-associated mutations (RAMs) among antiretroviral-naïve people with HIV (PWH) is important for the implementation of HIV treatment and control programmes. We analysed the trends of HIV-1 PDR after the introduction of second-generation integrase strand-transfer inhibitors (INSTIs) in 2016 in Taiwan, when single-tablet regimens of non-nucleoside reverse-transcriptase inhibitor (NNRTI-) and INSTI-based antiretroviral therapy became the preferred treatments.

Materials and methods
In this multicentre study, we included newly diagnosed, antiretroviral-naïve PWH who underwent tests for RAMs between 2016 and 2022. Pre-treatment genotypic resistance testing was performed, along with HIV-1 subtyping and determinations of plasma HIV RNA load and CD4 lymphocyte counts. RAMs were analysed using the Stanford University HIV Drug Resistance Database and only RAMs conferring at least low-level resistance were included.

Results
From 2016 to 2022, pre-treatment blood samples from 3001 newly diagnosed PWH, which constituted 24.3% of newly diagnosed PWH in Taiwan during the study period, were tested. Of the PWH with analysable gene sequences, the HIV-1 PDR prevalence to NNRTIs, nucleoside reverse-transcriptase inhibitors (NRTIs), first- and second-generation INSTIs and PIs was 10.0%, 2.1%, 2.5%, 0.6% and 0.4%, respectively. While the trends of PDR remained stable for NRTIs, INSTIs and PIs, there was a significantly increasing trend of PDR to NNRTIs from 6.0% in 2016% to 13.1% in 2022 (P = 0.001).

Conclusions
After the introduction of second-generation INSTIs in Taiwan, the trends of HIV-1 PDR to NRTIs and INSTIs remained low. Furthermore, there was no significant decrease of the prevalence of PDR toward NNRTIs between 2016 and 2022.
Understanding the effects of sub-inhibitory antibiotic concentrations on the development of β-lactamase resistance based on quantile regression analysis
Authors: Mira Portia , Guzman-Cole Candace , Meza Juan C 
Published: March 2024

Abstract

Aims
Quantile regression is an alternate type of regression analysis that has been shown to have numerous advantages over standard linear regression. Unlike linear regression, which uses the mean to fit a linear model, quantile regression uses a data set’s quantiles (or percentiles), which leads to a more comprehensive analysis of the data. However, while relatively common in other scientific fields such as economic and environmental modeling, it is infrequently used to understand biological and microbiological systems.

Methods and results
We analyzed a set of bacterial growth rates using quantile regression analysis to better understand the effects of antibiotics on bacterial fitness. Using a bacterial model system containing 16 variant genotypes of the TEM β-lactamase enzyme, we compared our quantile regression analysis to a previously published study that uses the Tukey’s range test, or Tukey honestly significantly difference (HSD) test. We find that trends in the distribution of bacterial growth rate data, as viewed through the lens of quantile regression, can distinguish between novel genotypes and ones that have been clinically isolated from patients. Quantile regression also identified certain combinations of genotypes and antibiotics that resulted in bacterial populations growing faster as the antibiotic concentration increased—the opposite of what was expected. These analyses can provide new insights into the relationships between enzymatic efficacy and antibiotic concentration.

Conclusions
Quantile regression analysis enhances our understanding of the impacts of sublethal antibiotic concentrations on enzymatic (TEM β-lactamase) efficacy and bacterial fitness. We illustrate that quantile regression analysis can link patterns in growth rates with clinically relevant mutations and provides an understanding of how increasing sub-lethal antibiotic concentrations, like those found in our modern environment, can affect bacterial growth rates, and provide insight into the genetic basis for varied resistance.
Analyzing time series to forecast hot rolled coil steel price in Spain by means of neural non-linear models
Authors: Alcalde Roberto , GarcÍa Santiago , Manzanedo Manuel , Basurto Nuño , de Armiño Carlos Alonso , Urda Daniel , Alonso Belén 
Published: March 2024

Abstract
In the industrial context, steel is a broadly-used raw material with applications in many different fields. Due to its high impact in the activity of many industries all over the world, forecasting its price is of utmost importance for a huge amount of companies. In this work, non-linear neural models are applied for the first time to different datasets in order to validate their suitability when predicting the price of this commodity. In particular, the NAR, NIO and NARX neural network models are innovatively applied for the first time to forecast the price of hot rolled steel in Spain. Besides these variety of models, different datasets consisting of a set of heterogenous variables from the last seven years and related to the price of this commodity are benchmarked and analyzed. The results showed that NARX is the best performing model when the price of raw materials used to produce steel and the stock market prices of three major global steel producing companies are employed as input to this predictive model. Consequently, this result may boost the application of Machine Learning in companies, in order to schedule the supplying operations according to the price forecasting.
Sacubitril/valsartan protective effect on induced intestinal ischemia/reperfusion injury via immune modulation of IL6/STAT1 pathway
Authors: Refaie Marwa Monier Mahmoud , Amin Entesar Farghly , Hassan Marwa Nadi , Rifaai Rehab Ahmed , Bayoumi Asmaa M A , Kamel Maha Yehia 
Published: March 2024

Abstract

Objectives
Intestinal ischemia reperfusion (IIR) is a critical emergency situation that needs immediate intervention. Small intestine is one of the most sensitive tissues to IR injury and it remains a highly morbid condition, with reported mortality rates ranging from 30% to 90%. Thus, we aimed to evaluate the suspected protective role of sacubitril/valsartan (SAC/VAL) on IIR injury.

Methods
Thirty-two adult male Wistar rats were used in our model and divided into four groups: sham group, SAC/VAL treated group without IIR, IIR group, and SAC/VAL treated group with IIR. SAC/VAL in a dose of 30 mg/kg was administered orally just before induction of IIR.

Key findings
SAC/VAL significantly ameliorated IIR-induced changes as it decreased malondialdehyde (MDA), tumor necrosis factor alpha (TNFα), angiotensin II (ANG II), interleukin 6 (IL 6), active caspase 3, and signal transducer- and activator-of transcription (STAT1). However, SAC/VAL administration significantly increased antioxidant parameters such as total antioxidant capacity (TAC), superoxide dismutase (SOD), and reduced glutathione (GSH). Moreover, alteration of the histological structure was observed in IIR group that was improved by SAC/VAL.

Conclusions
SAC/VAL prevents IIR-induced damage via modulation of renin angiotensin aldosterone system, antioxidant, anti-apoptotic, anti-inflammatory properties, and regulation of IL6/STAT1 pathway.
Prospective and systematic screening for invasive aspergillosis in the ICU during the COVID-19 pandemic, a proof of principle for future pandemics
Authors: van Grootveld Rebecca , van Paassen Judith , Claas Eric C J , Heerdink Laura , Kuijper Ed J , de Boer Mark G J , van der Beek Martha T ,   LUMC-COVID-19 Research Group
Published: March 2024

Abstract
The diagnostic performance of a prospective, systematic screening strategy for COVID-19 associated pulmonary aspergillosis (CAPA) during the COVID-19 pandemic was investigated. Patients with COVID-19 admitted to the ICU were screened for CAPA twice weekly by collection of tracheal aspirate (TA) for Aspergillus culture and PCR. Subsequently, bronchoalveolar lavage (BAL) sampling was performed in patients with positive screening results and clinical suspicion of infection. Patient data were collected from April 2020–February 2022. Patients were classified according to 2020 ECMM/ISHAM consensus criteria. In total, 126/370 (34%) patients were positive in screening and CAPA frequency was 52/370 (14%) (including 13 patients negative in screening). CAPA was confirmed in 32/43 (74%) screening positive patients who underwent BAL sampling. ICU mortality was 62% in patients with positive screening and confirmed CAPA, and 31% in CAPA cases who were screening negative. The sensitivity, specificity, positive and negative predictive value (PPV & NPV) of screening for CAPA were 0.71, 0.73, 0.27, and 0.95, respectively. The PPV was higher if screening was culture positive compared to PCR positive only, 0.42 and 0.12 respectively. CAPA was confirmed in 74% of screening positive patients, and culture of TA had a better diagnostic performance than PCR. Positive screening along with clinical manifestations appeared to be a good indication for BAL sampling since diagnosis of CAPA was confirmed in most of these patients. Prospective, systematic screening allowed to quickly gain insight into the epidemiology of fungal superinfections during the pandemic and could be applicable for future pandemics.
Nature versus nurture: distinguishing effects from stellar processing and chemical evolution on carbon and nitrogen in red giant stars
Authors: Roberts John D , Pinsonneault Marc H , Johnson Jennifer A , Zinn Joel C , Weinberg David H , Vrard Mathieu , Tayar Jamie , Stello Dennis , Mosser Benoît , Johnson James W , Cao Kaili , Stassun Keivan G , Stringfellow Guy S , Serenelli Aldo , Mathur Savita , Hekker Saskia , García Rafael A , Elsworth Yvonne P , Corsaro Enrico 
Published: March 2024

ABSTRACT
The surface [C/N] ratios of evolved giants are strongly affected by the first dredge-up (FDU) of nuclear-processed material from stellar cores. C and N also have distinct nucleosynthetic origins and serve as diagnostics of mixing and mass-loss. We use subgiants to find strong trends in the birth [C/N] with [Fe/H], which differ between the low-α and high-α populations. We demonstrate that these birth trends have a strong impact on the surface abundances after the FDU. This effect is neglected in current stellar models, which use solar-scaled C and N. We map out the FDU as a function of evolutionary state, mass, and composition using a large and precisely measured asteroseismic data set in first-ascent red giant branch (RGB) and core He-burning, or red clump (RC), stars. We describe the domains where [C/N] is a useful mass diagnostic and find that the RC complements the RGB and extends the range of validity to higher mass. We find evidence for extra mixing on the RGB below [Fe/H] = −0.4, matching literature results, for high-α giants, but there is no clear evidence of mixing in the low-α giants. The predicted signal of mass-loss is weak and difficult to detect in our sample. We discuss implications for stellar physics and stellar population applications.
The FAST Galactic Plane Pulsar Snapshot Survey – V. PSR J1901+0658 in a double neutron star system
Authors: Su W Q , Han J L , Yang Z L , Wang P F , Yuan J P , Wang C , Zhou D J , Wang T , Yan Y , Jing W C , Cai N N , Xie L , Xu J , Wang H G , Xu R X , You X P 
Published: March 2024

ABSTRACT
Double neutron star (DNS) systems offer excellent opportunities to test gravity theories. We report the timing results of PSR J1901+0658, the first pulsar discovered in the FAST Galactic Plane Pulsar Snapshot (GPPS) Survey. Based on timing observations by FAST over 5 yr, we obtain the phase-coherent timing solution and derive the precise measurements of its position, spin parameters, orbital parameters, and dispersion measure. It has a period of 75.7 ms, a period derivative of 2.169(6) × 10−19 s s−1, and a characteristic age of 5.5 Gyr. This pulsar is in an orbit with a period of 14.45 d and an eccentricity of 0.366. One post-Keplerian parameter, periastron advance, has been well-measured as being 0.00531(9) deg yr−1, from which the total mass of this system is derived to be 2.79(7) M⊙. The pulsar has the mass upper limit of 1.68 M⊙, so the lower limit for the companion mass is 1.11 M⊙. Because PSR J1901+0658 is a partially recycled pulsar in an eccentric binary orbit with such a large companion mass, it should be in a DNS system according to the evolution history of the binary system.