bluuebunny/crossref_metadata_2025 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

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

Rationale

Pathogenic (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.

Objectives

Investigate 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.

Methods

A 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.

Results

Individuals 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.

Conclusion

Distinguishing 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

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

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

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

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

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

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

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

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

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

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.
N2H+(1–0) as a tracer of dense gas in and between spiral arms
Authors: Fehér Orsolya , Ragan S E , Priestley F D , Clark P C , Moore T J T
Published: March 2024

Recent advances in identifying giant molecular filaments in Galactic surveys allow us to study the interstellar material and its dense, potentially star forming phase on scales comparable to resolved extragalactic clouds. Two large filaments detected in the 13CO/C18O(J = 3–2) Heterodyne Inner Milky Way Plane Survey (CHIMPS) survey, one in the Sagittarius-arm and one in an interarm region, were mapped with dense gas tracers inside a 0.06 square degrees area and with a spatial resolution of around 0.4 and 0.65 pc at the distance of the targets using the 30 m telescope of the Institut de Radioastronomie Millimétrique (IRAM) to investigate the environmental dependence of the dense gas fraction. The N2H+(1 − 0) transition, an excellent tracer of the dense gas, was detected in parsec-scale, elliptical clumps and with a filling factor of around 8.5  per cent in our maps. The N2H+-emitting areas appear to have higher dense gas fraction (e.g. the ratio of N2H+ and 13CO emission) in the interarm than in the arm which is opposite to the behaviour found by previous studies, using dust emission rather than N2H+ as a tracer of dense gas. However, the arm filament is brighter in 13CO and the infrared emission of dust, and the dense gas fraction determined as above is governed by the 13CO brightness. We caution that measurements regarding the distribution and fraction of dense gas on these scales may be influenced by many scale- and environment-dependent factors, as well as the chemistry and excitation of the particular tracers, then consider several scenarios that can reproduce the observed effect.
IgG4-related disease complicated with diffuse and chronic gastrointestinal inflammation leading to small intestinal perforation
Authors: Ino Kazuma , Arinuma Yoshiyuki , Akiya Masashi , Kajita Sabine , Okina Sosei , Sakamoto Junichi , Tanaka Tomoki , Matsueda Yu , Wada Tatsuhiko , Tanaka Sumiaki , Oku Kenji , Yamaoka Kunihiro
Published: March 2024

Immunoglobulin (Ig) G4–related disease (IgG4-RD) is a systemic inflammatory disease characterised by elevated serum IgG4, IgG4+ cell infiltration, storiform fibrosis, and obliterative phlebitis. While IgG4-RD can affect various organs, gastrointestinal tract involvement is less common. Here, we report a 70-year-old female with IgG4-RD complicated with diffuse and chronic gastrointestinal inflammation, which led to small intestinal perforation. She had been suffering from anorexia, abdominal pain, vomiting, and diarrhoea and hospitalised due to recurrent ileus. Consequently, she was referred due to small intestinal perforation required for surgical intervention. Pathology revealed acute and chronic inflammation with massive IgG4+ plasmacyte infiltration into mucosa of the small intestine and ischaemic change secondarily caused by chronic inflammation. Random biopsies from the mucosa of stomach, duodenum, ileum, and colon also revealed diffuse and massive IgG4+ plasmacyte infiltration in stomach, duodenum, small intestine, and colon. She was diagnosed with IgG4-RD based on the pathological findings and elevated serum IgG4 levels. Glucocorticoid rapidly ameliorated the symptoms. IgG4-RD may cause gastrointestinal manifestations, and histopathological assessment should be considered, even in the absence of specific characteristics of IgG4-RD.
Profiling the molecular and clinical landscape of glioblastoma utilizing the Oncology Research Information Exchange Network brain cancer database
Authors: Demetriou Alexandra N , Chow Frances , Craig David W , Webb Michelle G , Ormond D Ryan , Battiste James , Chakravarti Arnab , Colman Howard , Villano John L , Schneider Bryan P , Liu James K C , Churchman Michelle L , Zada Gabriel
Published: March 2024

Background

Glioblastoma exhibits aggressive growth and poor outcomes despite treatment, and its marked variability renders therapeutic design and prognostication challenging. The Oncology Research Information Exchange Network (ORIEN) database contains complementary clinical, genomic, and transcriptomic profiling of 206 glioblastoma patients, providing opportunities to identify novel associations between molecular features and clinical outcomes.

Methods

Survival analyses were performed using the Logrank test, and clinical features were evaluated using Wilcoxon and chi-squared tests with q-values derived via Benjamini-Hochberg correction. Mutational analyses utilized sample-level enrichments from whole exome sequencing data, and statistical tests were performed using the one-sided Fisher Exact test with Benjamini-Hochberg correction. Transcriptomic analyses utilized a student’s t-test with Benjamini-Hochberg correction. Expression fold changes were processed with Ingenuity Pathway Analysis to determine pathway-level alterations between groups.

Results

Key findings include an association of MUC17, SYNE1, and TENM1 mutations with prolonged overall survival (OS); decreased OS associated with higher epithelial growth factor receptor (EGFR) mRNA expression, but not with EGFR amplification or mutation; a 14-transcript signature associated with OS > 2 years; and 2 transcripts associated with OS < 1 year.

Conclusions

Herein, we report the first clinical, genomic, and transcriptomic analysis of ORIEN glioblastoma cases, incorporating sample reclassification under updated 2021 diagnostic criteria. These findings create multiple avenues for further investigation and reinforce the value of multi-institutional consortia such as ORIEN in deepening our knowledge of intractable diseases such as glioblastoma.
Shaking Hands and the Politics of Touch in Early Modern England
Authors: Walter John
Published: March 2024

Drawing on work in the social sciences on the handshake, this article examines the role of the handshake as a form of gestural communication and traces the changes in its relative importance in the ‘access rituals’ of early modern England. We lack a history of the handshake for early modern England. Such work as there is, is chronologically discontinuous and largely blind to the sociology of its performance. Working across the period from the later fifteenth into the eighteenth century, the article seeks to recover the chronological, spatial, social and gendered contours to the handshake. Discussing early modern understandings of the social and cultural meanings of touch and the hand, the article explores how performing a handshake could play a part in the representation, reproduction and negotiation of social and political relationships. Examining the micro-politics of shaking hands, the article offers a critical historical assessment of modern readings of the handshake as signalling friendship and social solidarity, analysing the changing significance of the ‘handshake entitlement’ as a ‘status-regulated’ gesture that helped both to enact and to challenge early modern social and political order.
Fluoritites Produced by Crystallization of Carbonate–Fluoride Magma
Authors: Stepanov Aleksandr S , Aminov Jovid , Odinaev Sharifjon , Iskandarov Farukh Sh , Jiang Shao-Yong , Karmanov Nikolai S
Published: March 2024

Fluorite-dominated rocks are occasionally found in association with carbonatites, but their geologic and petrologic relations are rarely reported. The Dunkeldyk area of the Pamir mountains in south-eastern Tajikistan contains dikes of distinctive rocks composed of calcite, fluorite, celestine-barite, sulfides, apatite, with minor quartz, biotite, and REE fluorcarbonates. The dikes have sharp contacts with the host (meta-)sedimentary rocks and layering with ribbons, ranging from fluorite-bearing calcite carbonatites to fluoritites (rocks with >50% fluorite). The fluoritites are characterized by high Ca, F, Ba, Sr, REE, and S coupled with anomalously low O. The geologic relations and textures suggest a magmatic origin of the dikes from melts close to calcite–fluorite eutectic that experienced nucleation-controlled differentiation during the crystallization of dikes and the formation of fluoritite cumulates in larger intrusions. The Dunkeldyk dikes demonstrate that sizable geological bodies of fluorite-dominated rocks could form from carbonate–fluoride melts originating from the differentiation of alkaline silicate magmas.
Political Alienation and the Trump Vote in the 2016 and 2020 US Presidential Elections
Authors: Allamong Maxwell B
Published: March 2024

Following Donald Trump’s surprising victory in the 2016 US presidential election, some popular and scholarly sources suggested that Trump’s candidacy may have been bolstered, in part, by the mobilization of “politically alienated” voters. This argument is puzzling, however, as certain forms of political alienation are often negatively related to political participation, making it unclear whether or how alienation may have been related to turnout and to support for Trump at the ballot box. I shed light on this puzzle using data from the American National Election Studies, which contain measures of two dimensions of political alienation: inefficacy and cynicism. With these data I examine how either dimension relates to turnout and to vote choice in 2016 and in 2020. Cynicism emerges as a positive predictor of both turnout and the Trump vote in 2016, but not in 2020. Inefficacy, however, does not positively predict turnout or the Trump vote in either election. I offer a potential explanation for the diminished relationship between cynicism and mobilization in the 2020 elections by applying a Structural Topic Model to open-ended survey responses about Trump, which reveals a substantial decrease in the salience of Trump’s “political outsider” qualities during his reelection bid.
Measuring Attentiveness in Self-Administered Surveys
Authors: Berinsky Adam J , Frydman Alejandro , Margolis Michele F , Sances Michael W , Valerio Diana Camilla
Published: March 2024

The surge in online self-administered surveys has given rise to an extensive body of literature on respondent inattention, also known as careless or insufficient effort responding. This burgeoning literature has outlined the consequences of inattention and made important strides in developing effective methods to identify inattentive respondents. However, differences in terminology, as well as a multiplicity of different methods for measuring and correcting for inattention, have made this literature unwieldy. We present an overview of the current state of this literature, highlighting commonalities, emphasizing key debates, and outlining open questions deserving of future research. Additionally, we emphasize the key considerations that survey researchers should take into account when measuring attention.
Attitudes toward Police and Police Spending
Authors: Sances Michael W
Published: March 2024

The Black Lives Matter movement focused scholarly and public attention on the politics of policing, but little is known about long-term trends in public opinion toward the police. I analyze three time series of attitudes toward police and police spending dating back as far as the 1960s: Gallup’s confidence in police question, the American National Election Studies’ feeling thermometer toward police, and the General Social Survey’s support for law enforcement spending question. The general public has become less positive toward police, and racial and partisan gaps have increased, in all three series. Partisan gaps are generally larger than racial gaps, and differences between white and Black Democrats have evolved in important ways. Divides on confidence and affect are more longstanding than divides on support for spending.
Sectorial Equidistribution of the Roots of x2 + 1 Modulo Primes
Authors: Musicantov Evgeny , Zehavi Sa’ar
Published: March 2024

The equation $x^2 + 1 = 0\mod p$ has solutions whenever p = 2 or $4n + 1$. A famous theorem of Fermat says that these primes are exactly the ones that can be described as a sum of two squares. The roots of the former equation are equidistributed is a beautiful theorem of Duke, Friedlander and Iwaniec. The angles associated to the representation of such prime as a sum of squares are equidistributed is a famous theorem of Hecke. We give a natural way to associate between roots and angles and prove that the joint equidistribution of the sequence of pairs of roots and angles is equidistributed as well. Our approach involves an automorphic interpretation, which reduces the problem to the study of certain Poincare series on an arithmetic quotient of $SL_2(\mathbb{R})$. Since our Poincare series have a nontrivial dependence on their Iwasawa θ-coordinate, they do not factor into functions on the upper half plane, as in the case studied by Duke et al.

Spectral analysis on these higher dimensional varieties involves the nonspherical spectrum, making this paper the first complete study of a nonspherical equidistribution problem, with an arithmetic application. A couple of notable challenges we had to overcome were that of obtaining pointwise bounds for nonspherical Eisenstein series and utilizing a non-spherical analogue of the Selberg inversion formula, which we believe may have further implications beyond this work.
Rheumatoid arthritis patients’ perspective on the use of prediction models in clinical decision-making
Authors: Messelink Marianne A , Fadaei Sina , Verhoef Lise M , Welsing Paco , Nijhof Nienke C , Westland Heleen
Published: March 2024

Objectives

A rapidly expanding number of prediction models is being developed, aiming to improve RA diagnosis and treatment. However, few are actually implemented in clinical practice. This study explores factors influencing the acceptance of prediction models in clinical decision-making by RA patients.

Methods

A qualitative study design was used with thematic analysis of semi-structured interviews. Purposive sampling was applied to capture a complete overview of the influencing factors. The interview topic list was based on pilot data.

Results

Data saturation was reached after 12 interviews. Patients were generally positive about the use of prediction models in clinical decision-making. Six key themes were identified from the interviews: (i) patients have a need for information about prediction models; (ii) factors influencing trust in model-supported treatment are described; (iii) patients envision the model to have a supportive role in clinical decision-making; (iv) patients hope to personally benefit from model-supported treatment in various ways; (v) patients are willing to contribute time and effort to contribute to model input; (vi) the effects of model-supported treatment on the relationship with the caregiver are discussed.

Conclusion

Within this study, RA patients were generally positive about the use of prediction models in their treatment, given some conditions were met and concerns addressed. The results of this study can be used during the development and implementation in RA care of prediction models in order to enhance patient acceptability.
Networked nexus of science diplomacy and domestic funding agency coordination: a case study of IntSam
Authors: Lundin Hans , Broström Anders , Geschwind Lars
Published: March 2024

This study explores the role of network administrative organizations (NAOs) in science diplomacy (SD) by means of a qualitative case study approach. The case in point is a Swedish government initiative to coordinate the internationalization efforts of domestic funding agencies. We examine how the NAO IntSam balances between governmental directives and agency autonomy. Utilizing primary data from semi-structured interviews supplemented by internal documents and policy reports, the analysis delves into the challenges and potential of NAOs in harmonizing top-down directives with agency autonomy. The findings highlight IntSam’s role in facilitating collaboration and aligning domestic and international policy landscapes, while also revealing inherent tensions due to divergent governmental and agency priorities. This study contributes to understanding the complexities of coordinating cross-border Science, Technology, and Innovation efforts, offering insights into the nuances, potentials, and limitations of NAOs in the realm of SD.
Precision medicine to personalize medicine in allergic airway disease
Authors: Kim Jean
Published: March 2024

Purpose of review

The purpose of this study is to understand the approach to precision medicine and personalized medicine in the management of allergic airway disease.

Recent findings

Identification of biomarkers as key tools used in precision medicine has led to the development of multiple biologic drugs being used as new treatments for allergic airway disease.

In addition to these advances, there is still much needed effort to improve the feasibility and utility of integrating biologic omics data of precision medicine with physicochemical, behavioral, psychological, and social data to deliver optimized treatments that is personalized for each individual.
Combined Wrist Extensor Tenodesis and Tendon Transfers for Severe Spastic Flexed Wrist Deformity: Surgical Technique and Case Series
Authors: Pino Paula A. , Crowe Christopher S. , Wu Kitty Y. , Rhee Peter C.
Published: March 2024

Spastic wrist flexion deformities both limit the functional use of the hand for grasp and pinch producing a stigmatizing appearance. Tendon transfers and total wrist arthrodesis are treatment options for this condition depending on the patient’s characteristics, the latter the most commonly used in patients with severe wrist flexion deformities. Tendon transfers alone in this scenario have the tendency for recurrent deformity due to tenorrhaphy failure or soft tissue creep and resultant loss of tension. Total wrist arthrodesis is a more invasive procedure, which can have hardware or fusion problems and that is irreversible. We propose a novel technique that incorporates a distally based wrist extensor tendon slip and suture tape tenodesis to the distal radius. The rationale of this technique is to act as a protective, internal splint to prevent recurrent deformity after primary or revision tendon transfer for moderate to severe spastic flexed wrist deformities, avoiding the need to perform a total wrist arthrodesis.
TIGIT Blockade Reshapes the Tumor Microenvironment Based on the Single-cell RNA-Sequencing Analysis
Authors: Lang Yanyan , Huang Hao , Jiang Hongwei , Wu Shaoxian , Chen Yaping , Xu Bin , Liu Yingting , Zhu Dawei , Zheng Xiao , Chen Lujun , Jiang Jingting
Published: March 2024

Immune checkpoint blockade therapy is a pivotal approach in treating malignant tumors. TIGIT has emerged as a focal point of interest among the diverse targets for tumor immunotherapy. Nonetheless, there is still a lack of comprehensive understanding regarding the immune microenvironment alterations following TIGIT blockade treatment. To bridge this knowledge gap, we performed single-cell sequencing on mice both before and after the administration of anti-TIGIT therapy. Our analysis revealed that TIGIT was predominantly expressed on T cells and natural killer (NK) cells. The blockade of TIGIT exhibited inhibitory effects on Treg cells by downregulating the expression of Foxp3 and reducing the secretion of immunosuppressive cytokines. In addition, TIGIT blockade facilitated the activation of NK cells, leading to an increase in cell numbers, and promoted cDC1 maturation through the secretion of XCL1 and Flt3L. This activation, in turn, stimulated the TCR signaling of CD8+T cells, thereby enhancing their antitumor effect. Consequently, anti-TIGIT therapy demonstrated substantial potential for cancer immunotherapy. Our research provided novel insights into future therapeutic strategies targeting TIGIT for patients with cancer.
Internal m6A and m7G RNA modifications in hematopoietic system and acute myeloid leukemia
Authors: Zhang Xiaoxu , Ma Yanni , Yu Jia , Su Rui , Wang Xiaoshuang
Published: March 2024

Epitranscriptomics focuses on the RNA-modification-mediated post-transcriptional regulation of gene expression. The past decade has witnessed tremendous progress in our understanding of the landscapes and biological functions of RNA modifications, as prompted by the emergence of potent analytical approaches. The hematopoietic system provides a lifelong supply of blood cells, and gene expression is tightly controlled during the differentiation of hematopoietic stem cells (HSCs). The dysregulation of gene expression during hematopoiesis may lead to severe disorders, including acute myeloid leukemia (AML). Emerging evidence supports the involvement of the mRNA modification system in normal hematopoiesis and AML pathogenesis, which has led to the development of small-molecule inhibitors that target N6-methyladenosine (m6A) modification machinery as treatments. Here, we summarize the latest findings and our most up-to-date information on the roles of m6A and N7-methylguanine in both physiological and pathological conditions in the hematopoietic system. Furthermore, we will discuss the therapeutic potential and limitations of cancer treatments targeting m6A.
Comparative Effectiveness and Safety of Intermittent, Repeated, or Continuous Use of Levosimendan, Milrinone, or Dobutamine in Patients With Advanced Heart Failure: A Network and Single-Arm Meta-analysis
Authors: Zhang Xue , Wang Zhongsu , Zhang Le , Zhao Xia , Han Yi
Published: March 2024

The aim of this study was to synthesize the available evidence regarding differences in the long-term safety and efficacy of intermittent, repeated, or continuous palliative inotropic therapy among patients with advanced heart failure. We systematically searched the PubMed, Embase, and Cochrane Library electronic databases, with a cutoff date of November 23, 2023, for studies reporting outcomes in adult patients with advanced heart failure treated with intermittent, repeated, or continuous levosimendan, milrinone, or dobutamine. Forty-one studies (18 randomized controlled trials and 23 cohort studies) comprising 5137 patients met the inclusion criteria. The results of the network meta-analysis of randomized controlled trials showed that levosimendan had significant advantages over milrinone or dobutamine in reducing mortality and improving left ventricular ejection fraction. A single-arm meta-analysis also indicated that levosimendan had the lowest mortality and significantly improved B-type brain natriuretic peptide and left ventricular ejection fraction. Regarding safety, hypotension events were observed more frequently in the levosimendan and milrinone groups. However, the current evidence is limited by the heterogeneity and relatively small sample size of the studies.
Bad behavior in healthcare: an insidious threat to patients, staff, and organizations
Authors: Crowe Liz , Riley Christine M.
Published: March 2024

Purpose of review

‘Bad’ or unprofessional behavior (UPB) destroys communication, teamwork, and professional wellbeing, presenting a significant threat to patients and staff. Understanding what constitutes ‘bad’ or UPB and creating broad accountability for its cessation is imperative to patient-centered care and the survival of the multidisciplinary health workforce.

Recent findings

Despite organizational and legislative commitments to provide well tolerated work environments, UPB is endemic in healthcare and continues to harm patients, staff, and organizations. Historically, categories of UPB have been researched separately which dilutes the problem. Typically, these behaviors cluster, are interchangeable, and are committed by same perpetrators. Women, junior staff, and minority groups remain the most prevalent targets. Even low intensity UPBs among health staff dramatically impacts risk to patient lives, limits quality care, and destroys staff wellbeing. Targeted interventions must address all five roles impacted by UPBs: the target, patients, bystanders, the perpetrator, and the organization to effectively eliminate UPBs. Organizational leaders must demonstrate and uphold organizational values and be swift in addressing UPB to limit the impact on teams and patients.

UPB in the healthcare setting presents a multifactorial threat to patients, staff, and organizations. To ensure the delivery of high-quality patient care, and the wellbeing of the health workforce it is crucial to understand the insidious impact of UPB and target interventions across all five roles.