bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mild autonomous cortisol secretion in patients with aldosterone-producing adenoma and risk for cardiac remodeling and diastolic dysfunction
Authors: Tsai Cheng-Hsuan , Liao Che-Wei , Wu Xue-Ming , Chen Zheng-Wei , Pan Chien-Ting , Chang Yi-Yao , Lee Bo-Ching , Chou Chia-Hung , Chang Chin-Chen , Wu Vin-Cent , Hung Chi-Sheng , Vaidya Anand , Lin Yen-Hung 
Published: January 2025

Abstract

Background
Mild autonomous cortisol secretion (MACS) is common in adrenal adenomas, including patients with primary aldosteronism (PA) with aldosterone-producing adenomas (APA). This study investigated the impact of MACS on cardiac remodeling and diastolic dysfunction in patients with APA.

Methods
We prospectively enrolled 483 patients with APA. MACS was defined as a cortisol level &gt;1.8 μg/dL after an overnight dexamethasone-suppression test (DST). Clinical, biochemical, and echocardiographic data were collected at baseline and one-year following targeted treatments.

Results
In this prospective cohort, 21% of patients with APA had concurrent MACS. Patients with MACS were older, had a higher prevalence of diabetes, larger adrenal tumor size, higher left ventricular mass index (LVMI), and worse diastolic function (E/e′). Multivariable linear regression analysis showed that concurrent MACS with APA was an independent risk factor for higher LVMI and worse E/e′. Among patients who underwent adrenalectomy, both those with and without MACS showed significant improvements in LVMI and E/e′. In contrast, among patients who received mineralocorticoid receptor antagonist (MRA) treatment, significant LVMI improvement was only observed in patients without MACS. MRA therapy did not improve E/e′ regardless of the presence or absence of MACS.

Conclusions
The presence of MACS in patients with PA was associated with worse cardiac hypertrophy and diastolic dysfunction. Surgical adrenalectomy was able to effectively reverse cardiac remodeling in patients with PA and concurrent MACS; however, MRA therapy was not associated with significant improvements in cardiac function. These findings highlight the independent deleterious effects of cortisol on cardiovascular disease in PA.
Hypertrophic cardiomyopathy: prevalence of disease-specific red flags
Authors: Maurizi Niccolò , Monda Emanuele , Biagini Elena , Field Ella , Passantino Silvia , Dall' Aglio Gabriella , Fumagalli Carlo , Antiochos Panagiotis , Skalidis Ioannis , Pieroni Maurizio , Argirò Alessia , Girolami Francesca , Cecchi Franco , Barbey Frederic , Monney Pierre , Elliott Perry M , Kaski Juan Pablo , Limongelli Giuseppe , Olivotto Iacopo 
Published: January 2025

Abstract

Background and Aims
The European Society of Cardiology guidelines recommend a systematic search for diagnostic clues or ‘red flags’ (RFs) in patients with hypertrophic cardiomyopathy (HCM) to better tailor disease management. To date, the prevalence and clinical significance of RF associated with HCM phenotypes in different clinical settings are unknown.

Methods
The study cohort comprised 818 patients with a clinical diagnosis of HCM [479 (62%) males, mean age 49 ± 21 years] referred to four European centres. Pre-specified RFs were categorized into one of five domains: (i) family history; (ii) physical examination; (iii) electrocardiography; (iv) echocardiography; and (v) laboratory.

Results
A total of 318 (39%) patients had a pathogenic or likely pathogenic sarcomere gene variant; 240 (29%) a TTR and GLA variant; 154 (19%) a syndromic cause; and 106 (13%) no identifiable cause. In the overall cohort, 2979 RFs were identified. Of these, 1018 (34%) were identifiable from clinical history and examination alone (generalist setting) and 1961 (66%) by 12-lead electrocardiogram and echocardiography (cardiologist’s office). Non-sarcomeric patients were diagnosed more often aged &lt;20 and after 60 years (476/500, 95%). Syndromic diseases such as Rasopathies, inherited metabolic disorders, and mitochondrial disorders were diagnosed in neonatal/early childhood (mean age 3 ± 2 years), whereas patients with Danon disease, Friedreich’s ataxia, Noonan syndrome, and PRKAG2 cardiomyopathy were identified mostly during adolescence (mean age 16 ± 8 years). Non-cardiac RFs identified by clinical history, physical examination, and routine laboratory testing were most frequent in patients with HCM caused by Rasopathies, inherited metabolic disorders, and mitochondrial disorders (48%, 47%, and 57%, respectively). Physical RFs were almost exclusively observed in patients with a definite non-sarcomeric aetiology [348/350 (99%)]. On the contrary, most RFs associated with geno-positive and geno-negative HCM were derived from electrocardiogram and echocardiography [692/990 (70%) and 332/375 (88%), respectively].

Conclusions
Red flags are a common finding in patients presenting with HCM, most commonly non-cardiac in non-sarcomeric aetiology and cardiac in sarcomeric HCM. Over 34% of RF, most relevant to rare HCM phenocopies, can be potentially detected in a generalist setting. Investing in high-touch-low tech, widespread awareness for HCM-related RF may provide substantial advantage in terms of diagnostic yield and appropriate use of resources.
Effects of changes to income tax and devolved benefits in Scotland on health inequalities: a modelling study
Authors: Richardson Elizabeth , Walsh David , McCartney Gerry , Pulford Andrew , Robinson Mark 
Published: January 2025

Abstract
There is a well-understood relationship between inequalities in income and health. We assessed how changes to income tax and social security—options recently devolved to the Scottish Government—could affect income and life expectancy inequalities. We used the microsimulation model UKMOD to estimate policies’ effects on household income distribution by socioeconomic deprivation, compared to baseline (Scottish income tax schedule for 2022/23). We then used the ‘Triple I’ (Informing Interventions to reduce health Inequalities) scenario modelling approach to estimate mortality effects for the income changes and calculated inequalities in life expectancy at birth. Scenario health impacts were determined largely by how much money they gave or took from households in the most deprived areas. Policies that increased incomes for households in deprived areas tended to reduce inequalities in life expectancy. Although we found this also applied to tax-cutting policies that increased income inequality, our estimates did not account for the public spending cuts that these costly policies would necessitate and their likely widening effect on health inequalities. Combining the best-performing (i.e. greatest positive impact) revenue-generating and revenue-spending policies we modelled—tax increases targeted at high earners and a doubling the value of social security benefits—would generate net revenue while reducing income inequality by approximately 10% and inequalities in life expectancy by 8% to 9%, but sizeable inequalities would remain. A multifaceted approach based on combinations of policies—including, but not limited to, bolder income tax measures—is required to achieve meaningful reductions in inequalities.
Reference genome of Calochortus tolmiei Hook. & Arn. (Liliaceae), a cat's ear mariposa lily
Authors: Landis Jacob B , Harden Julianna J , Eifler Evan , Buttelman Gretta L , Hernández Adriana I , Givnish Thomas J , Strickler Susan R , Specht Chelsea D 
Published: January 2025

Abstract
Calochortus tolmiei Hook. & Arn., a bulbous monocot with cat's ear flowers in the angiosperm family Liliaceae, is a perennial herb native to northern California, Oregon, and Washington. Calochortus exhibits substantial morphological and karyotype diversity with multiple floral forms and a haploid chromosome number varying from 6 to 10. Here, we present the first high-quality reference assembly in Liliaceae for C. tolmiei, with a scaffolded assembly of 2.9 Gb with an N50 of 296 Mb. Notably, 92% of the assembled genome is scaffolded into 10 pseudomolecules, matching the documented chromosome count of C. tolmiei. The genome contains 31,049 protein-coding genes, with 86.2% being functionally annotated. The closest reference-quality genome assembly to C. tolmiei is from Chionographis japonica (Willd.) Maxim. (Melianthiaceae), which diverged ∼83 Mya, providing a valuable genomic resource in the Liliales, an order which lacks genomic resources.
Disentangling Selection Into Mode From Mode Effects
Authors: O’Muircheartaigh Colm , Schumm L Philip , English Ned , Curtis Becki 
Published: January 2025

Abstract

Objectives
We investigate the impact of data collection mode on responses to variables in the National Social Life, Health, and Aging Project (NSHAP) Round 4 and discuss how potential mode differences should (and should not) be addressed in substantive analyses.

Methods
Among the set of respondents who were eligible to be contacted remotely in Round 4, we randomly selected 398 to be contacted instead for an in-person interview. We compare response rates and the distributions of selected key outcomes among those 398 respondents to those among the control group who were initially approached remotely. In contrast, we compared all R4 respondents according to the mode in which they completed the interview, including those not part of the randomized experiment.

Results
Among those included in the experiment, there was no evidence of systematic differences in responses to physical and mental health questions between remote and in-person modes, nor in responses to number recall measures. In-person respondents scored moderately lower on cognitive function measures requiring careful attention to a figure and/or task, though this difference became less with each similar item. Remote respondents named fewer social network members. Comparing all respondents according to their final mode yielded substantially different results in all cases.

Discussion
Mode did not appear to affect reports of physical and mental health based on a randomized comparison, though it did moderately affect other items in predictable ways. Naïve estimates of mode effects based on comparing all respondents according to mode yielded misleading results, and should not be used to adjust for mode differences in analyses.
Interleukin 6 Is Significantly Increased in Severe Pneumonia After Allo-Hematopoietic Stem Cell Transplantation and Might Induce Lung Injury via IL-6/sIL-6R/JAK1/STAT3 Pathway
Authors: Zhou Jing-Rui , Liao Yi , Cao Le-Qing , Ma Rui , He Yun , Li Na , Zhu Dan-Ping , Zhao Xiao-Su , Huang Xiao-Jun , Sun Yu-Qian 
Published: January 2025

Abstract

Background
Severe pneumonia after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with high mortality. Given that cytokines, including interleukin 6 (IL-6), play a critical role in immune-mediated organ injury in patients with severe coronavirus disease 2019 (COVID-19), we hypothesized that cytokines may also contribute to the pathogenesis of severe pneumonia after allo-HSCT. This study aimed to investigate the role of IL-6 in severe pneumonia after allo-HSCT and explore its underlying mechanism.

Methods
Serum cytokine levels were prospectively measured in patients with severe and nonsevere pneumonia following allo-HSCT. A mouse model of acute lung injury (ALI) and in vitro experiments using primary murine pulmonary microvascular endothelial cells (PMVECs) were conducted to assess the effects of IL-6 blockade, the mechanism of IL-6 in ALI, and immune-induced ALI.

Results
Serum IL-6 and soluble IL-6 receptor (sIL-6R) levels were higher in the severe pneumonia group than in the nonsevere group and were associated with disease progression. In a mouse model, preventive IL-6 blockade reduced ALI and improved survival. In vitro, the IL-6 trans-signaling complex caused more severe damage to mouse PMVECs than the classical signaling pathway. Soluble glycoprotein 130 and ruxolitinib effectively blocked the JAK1/STAT3 pathway activated by IL-6 trans-signaling in mouse PMVECs and reduced downstream inflammatory responses.

Conclusions
IL-6 levels were elevated in patients with severe pneumonia after allo-HSCT and were linked to disease progression. This injury may be driven by the IL-6/sIL-6R/JAK1/STAT3 pathway. This preliminary study suggests that targeting the IL-6 trans-signaling pathway may be a promising therapeutic approach for severe pneumonia/ALI following allo-HSCT.
Estimation for Nearest Neighbor Imputed Survey Data
Authors: Xia Xintao , Zhang Xiaofei , Fuller Wayne A 
Published: January 2025

Abstract
Nearest neighbor imputation is a popular procedure used to complete missing records. However, the nearest neighbor imputation estimator suffers from a bias that increases as the dimension of the matching variable increases. We study estimators that are model unbiased and have the hot-deck property. Estimation for domains is discussed. In the simulation study for the population mean, a proposed estimator is less biased and more efficient than the nearest neighbor estimator. The suggested replication variance estimator does not require repeated imputation and is appropriate for vectors with different missing patterns. In the simulation, the variance estimator gives confidence intervals with coverage rates close to the nominal level.
Engineered initiator tRNAs can effectively start translation at non-AUG start codons and diversify N-terminal amino acids for mRNA Display
Authors: Helmling Christina , Chan Alix I , Cunningham Christian N 
Published: January 2025

Abstract
mRNA display is an effective tool to identify high-affinity macrocyclic binders for challenging protein targets. The success of an mRNA display selection is dependent on generating highly diverse libraries with trillions of peptides. While translation elongation can canonically accommodate the 61 proteinogenic triplet codons, translation initiation is restricted to the native start codon AUG. Here, we investigate the ability of the Escherichia coli ribosome to initiate translation for 31 initiator tRNA (tRNAini) anticodon mutants at their respective cognate start codon using a NanoBiT translation assay. We show that the ability of those anticodon mutant tRNAsini to initiate translation is highly variable and is, in part, inhibited by tRNA misfolding induced by the anticodon mutations. We demonstrate based on two distinct misfolding patterns that translation efficiency can be effectively restored by introducing additional mutations that restore the active tRNA fold. We then used 10 of the engineered tRNAsini in a mutational analysis experiment for three reported macrocyclic peptides binding to Ubiquitin Specific Protease 7 (USP7). The observed enrichment of peptides correlates strongly with dissociation constants measured by surface plasmon resonance, and provides insights into the structure–activity relationship of the N-terminal amino acid without the requirement for peptide synthesis.
Cre-Lox miRNA-delivery technology optimized for inducible microRNA and gene-silencing studies in zebrafish
Authors: Guo Fangfei , Tromp Alisha , Wang Haitao , Hall Thomas E , Giacomotto Jean 
Published: January 2025

Abstract
While many genetic tools exist for zebrafish, this animal model still lacks robust gene-silencing and microRNA-delivery technologies enabling spatio-temporal control and traceability. We have recently demonstrated that engineered pri-miR backbones can trigger stable gene knockdown and/or express microRNA(s) of choice in this organism. However, this miRNA-expressing technology presents important limitations. First, to trigger potent knockdown(s), multiple synthetic-miRNAs must be expressed simultaneously, compromising the co-expression of fluorescent marker(s) and knockdown traceability. Second, when gene(s) knockdown triggers significant phenotypes, like homozygous mutants with severe early phenotypes, it is difficult, if not impossible, to maintain transgenic carriers. To solve these problems and provide a mature RNAi and microRNA-delivery technology, we have generated new RNAi reagents and an inducible delivery system based on the Cre/Lox technology. This system allows the creation of asymptomatic/silent carriers, easing the production of embryos with potent knockdowns that can be traced and spatiotemporally controlled. We further demonstrated the utility of this approach by establishing novel inducible and tissue-specific models of spinal muscular atrophy, opening new avenues for studying smn1-gene function and pathogenicity. All in all, these materials and techniques will be invaluable in studying microRNA biology and in modelling or tackling conditions in which gene dosage is key.
Perceived Harm of Vaping Relative to Smoking and Associations With Subsequent Smoking and Vaping Behaviors Among Young Adults: Evidence From a UK Cohort Study
Authors: East Katherine , Taylor Eve , McNeill Ann , Bakolis Ioannis , Taylor Amy E , Maynard Olivia M , Munafò Marcus R , Khouja Jasmine 
Published: January 2025

Abstract

Introduction
There is a lack of evidence on whether vaping harm perceptions can predict vaping and smoking behaviors among young adults in the United Kingdom. We aimed to assess whether the perceived harm of vaping relative to smoking is associated with subsequent changes in vaping and smoking behaviors in this population.

Methods
Data were from the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective cohort study. Longitudinal associations were assessed between the perceived harm of vaping relative to smoking at baseline (approximately 24 years old; Nov’15–Aug’17) and the following smoking/vaping outcomes at follow-up (approximately 30 years old; May–Oct’22): (1) stopping smoking, (2) initiation of ever smoking and/or vaping, and (3) uptake of past 30-day smoking and/or vaping. Multinomial logistic regressions were used, adjusting for sociodemographic factors.

Results
Among young adults who smoked but did not vape at baseline (n = 687), the perception that vaping is less harmful than smoking (vs. equally/more harmful, or don’t know) was associated with stopping smoking and now vaping at follow-up (adjusted Relative Risk Ratio (aRRR)=1.69, 95%CI = 1.02 to 2.81, p = .04). Initiation of ever smoking/vaping, or uptake of past 30-day smoking/vaping, were not common during the study period and there was little evidence that these outcomes were associated with relative vaping harm perceptions at baseline.

Conclusions
Among young adults who smoke, perceiving vaping as less harmful than smoking was associated with switching from smoking to vaping six years later. Few young adults who did not smoke or vape initiated these behaviors during the study period.

Implications
This is the first study in England to find that young adults who smoked and who accurately perceived vaping as less harmful than smoking were more likely to switch to vaping 6 years later. This is consistent with prior studies among adults and highlights the need for interventions to improve the pervasive misperceptions about vaping that are currently observed among young adults who smoke.
A first-in-human study of JNJ-70218902, a bispecific T-cell-redirecting antibody against TMEFF2 in metastatic castration-resistant prostate cancer
Authors: Calvo Emiliano , Doger Bernard , Carles Joan , Peer Avivit , Sarid David , Eigl Bernhard J , Avadhani Anjali , Yao David , Lin Vincent , Wu Shujian , Jaiprasart Pharavee , Loffredo John , Tamegnon Monelle , Xu Weichun , Xie Hong , Hansen Aaron R 
Published: January 2025

Abstract

Background
Metastatic castration-resistant prostate cancer (mCRPC) has a poor prognosis, necessitating the investigation of novel treatments and targets. This study evaluated JNJ-70218902 (JNJ-902), a T-cell redirector targeting transmembrane protein with epidermal growth factor-like and 2 follistatin-like domains 2 (TMEFF2) and cluster of differentiation 3, in mCRPC.

Patients and methods
Patients who had measurable/evaluable mCRPC after at least one novel androgen receptor–targeted therapy or chemotherapy were eligible. Participants received subcutaneous JNJ-902 0.3, 1.0, 1.5, 3.0, or 6.0 mg once weekly (QW) or 2.0, 3.0, 4.0, or 6.0 mg biweekly (Q2W). Study objectives included assessment of safety, pharmacokinetics, immunogenicity, and preliminary efficacy.

Results
Eighty-two participants were enrolled to receive at least one dose of JNJ-902 (QW; n = 38; Q2W; n = 44). Median duration of treatment was 1.91 (0.0-19.4) months across dosing groups. All participants experienced at least one treatment-emergent adverse event (TEAE) and 76 (92.7%) experienced treatment-related TEAEs. Fourteen participants (17.1%) experienced a TEAE that led to study discontinuation, of which 3 (3.7%) were related to JNJ-902. Dose-limiting toxicities were observed in 2 participants (2.4%). Five participants (15.2%) with measurable disease had a confirmed partial response and 10 participants (12.2%) had ≥50% decrease from baseline prostate-specific antigen levels. Clinical activity was not dose related and no clear exposure-response relationship was observed.

Conclusions
In this study, dose escalation was limited by emerging dose-limiting toxicities. Although a recommended phase II dose was not determined, findings indicate TMEFF2 to be a potential target in mCRPC that warrants further investigation.
Steroid-refractory immune mediated hepatitis managed with budesonide in patients with metastatic melanoma: proof of concept and literature review
Authors: Kankaria Roma A , Johnson Douglas B 
Published: January 2025

Abstract
Immune checkpoint inhibitors (ICIs) have advanced the treatment of metastatic melanoma. However, some patients develop ICI-associated toxicities like hepatitis (ie, immune-mediated hepatitis; IMH). Although these toxicities usually resolve with steroids, steroid-refractory events may occur, which may be a major source of morbidity and mortality without obviously defined treatment algorithms. Herein, we present 2 patients with metastatic melanoma who had IMH that was steroid-refractory and only partially mycophenolate-responsive, but fully resolved with budesonide. The case suggests that budesonide is a potential option to treat IMH that is refractory to standard treatments, but further investigation in a larger series is needed to identify the most optimal setting for budesonide use.