bluuebunny/crossref_metadata_2025 huggingface dataset:
CHRNA5-A3-B4, CYP2A6, and DBH Genetic Associations With Smoking Cessation Throughout Adulthood Within Two Longitudinal Studies of Women
Authors: Jones Stephanie K , Alberg Anthony J , Wallace Kristin , Froeliger Brett , Carpenter Matthew J , Wolf Bethany J
Published: December 2024

Introduction

Genetic studies of smoking cessation have been limited by short-term follow-up or cross-sectional design. Within seven genes (CHRNA3, CHRNA5, CHRNB2, CHRNB4, DRD2, DBH, and CYP2A6) influencing biological mechanisms relevant to smoking, this study aimed to identify single nucleotide polymorphisms (SNPs) associated with smoking cessation throughout up to 38 years of follow-up.

Aims and Methods

Participants were from two all-female cohort studies, Nurses’ Health Study (NHS) (n = 10 017) and NHS-2 (n = 2793). For 132 SNPs providing coverage of these genes, genotype associations with the probability of quitting smoking over time were evaluated using generalized estimating equations models. For SNPs reaching nominal statistical significance (p < .05) within NHS, NHS-2 was used as the replication cohort to control for multiple testing (false discovery rate [FDR] < 0.05). SNP genotype by smoking intensity (lifetime light vs. non-light smoking) interactions were also evaluated.

Results

Five SNPs identified in NHS were replicated in NHS-2 with FDR < 0.05. Women with the minor alleles of CHRNA5 SNPs rs637137 (odd ratio [OR] = 1.21) and rs503464 (OR = 1.24) had increased odds of cessation. Women with the minor alleles of CYP2A6 SNPs rs56113850 (OR = 0.81) and rs56267346 (OR = 0.82) and DBH SNP rs6479643 (OR = 0.78) had lower odds of cessation throughout adulthood. An interaction with smoking intensity was indicated for three SNPs, CHRNB4 rs4887074, CHRNA3 SNP rs77438700, and CHRNA5 SNP rs76474922.

Conclusion

Genetic associations with smoking cessation over decades of follow-up were observed and may guide targeted approaches for smokers most at risk for long-term relapse.

Implications

This study identified single nucleotide polymorphisms within CHRNA5-A3-B4, CYP2A6, and DBH that were associated with smoking cessation in women over decades of follow-up. This study is the first to examine these genetic associations over years of follow-up. Some associations were novel while others replicated previous findings from short-term studies for the first time. Potential differences in some associations between light and non-light smokers were also observed. Genetic factors associated with long-term smoking behavior may help inform interventions modeled on long-term chronic disease management approaches; specifically, targeted maintenance interventions to sustain abstinence could be implemented among high-risk smokers.
A Stop-Smoking Strategy After Cervical Cancer Screening: Results of a Cluster-Randomized Controlled Trial in Dutch General Practice
Authors: Mansour Marthe B L , Crone Mathilde R , van Weert Henk C , Chavannes Niels H , van Asselt Kristel M
Published: December 2024

Introduction

This study aimed to assess whether brief stop-smoking advice given to women who smoke and visit their general practice for cervical cancer screening improves smoking cessation outcomes.

Aims and Methods

This two-arm cluster-randomized controlled trial was conducted in 75 Dutch general practices. Participants in the intervention group received brief stop-smoking advice based on the Ask-Advise-Connect method, delivered by a practice assistant. Patient-reported outcomes were measured at 6 months: undertaking a serious quit attempt of at least 24 hours during follow-up (primary outcome), 7-day point prevalence abstinence at 6 months, reduction in number of cigarettes smoked, increase in motivation to quit smoking, exposure to advice or support, and other psychological and behavioral measurements.

Results

There was no significant difference in undertaking a serious quit attempt between the intervention (39.8% of n = 266) and control group (36.0% of n = 214), odds ratio 1.18 (95% confidence intervals: 0.80–1.72, p = .41). Neither did the point prevalence abstinence significantly differ between groups: 21.1% versus 16.3%, odds ratio 1.38 (95% confidence interval: 0.83–2.29, p = .21). Although nonsignificant, the direction of effects for the aforementioned outcomes was in favor of the intervention group. The reduction in the number of cigarettes smoked and increase in motivation to quit did not differ between groups. The uptake of cessation counseling was higher in the intervention (14.7%) than in the control group (2.8%).

Conclusions

A brief stop-smoking strategy after the smear test for cervical screening might encourage women who smoke to attempt quitting and seek cessation counseling, but a significant effect could not be demonstrated in this trial.

Implications

The results of this cluster-randomized trial suggest that brief advice to stop-smoking delivered by a practice assistant after routine cervical screening in general practice might encourage women who smoke to attempt quitting, but a significant effect could not be proven. Also, women who receive advice show a higher uptake of professional cessation counseling compared to their controls. Providing brief advice after the cervical smear might therefore be a useful opportunistic approach to stimulate cessation in women who smoke.
“What can I do? fight him?” Perceptions and Experiences in Reducing Secondhand Smoke Exposure During Pregnancy: A Qualitative Study Among Israeli Women
Authors: Rodnay Maya , Agbaria Nisreen , Neumark Yehuda , Guri-Scherman Anne-Laure Yehudit , Bar Zeev Yael
Published: December 2024

Introduction

Secondhand smoke (SHS) exposure during pregnancy is associated with negative health outcomes. We aimed to explore Israeli pregnant women’s perspectives on SHS exposure, with a focus on barriers and enablers to reducing SHS exposure at home and in the car.

Aims and Methods

Qualitative semi-structured telephone interviews with 68 women—54 Jewish and 14 Arab. Inclusion criteria: pregnant or up to 12 months post-partum; living with a person who smokes; age 18-45; Hebrew or Arabic speakers. Participants could be from any smoking status. Interviews were analyzed according to a reflective and collaborative thematic approach supported by the Capability (C) Opportunity (O) Motivation (M)-Behavior model.

Results

Participants knew SHS is harmful, but a lack of specific knowledge (C) was evident across all smoking status groups and population groups (Jewish, Arab). Women harbored misconceptions regarding their SHS exposure (C), employing ineffective strategies to eliminate exposure. Many perceived smoking as a significant source of tension in their relationship with their partners (M). Women described feeling uncomfortable asking people to not smoke around them (O) and bemoaned the lack of support from health professionals (O). Women who never smoked or formerly smoked described situations where they felt trapped and helpless. Specifically, Arab participants reported social isolation (O). The living environment (eg, building with no elevator) was a commonly mentioned barrier to reduce home SHS exposure (O).

Conclusions

Despite high motivation, the low level of knowledge and negotiation skills, misconceptions about exposure and effective strategies, together with insufficient support lead to behaviors resulting in high SHS exposure.

Implications

This research explored women’s experiences of SHS exposure during pregnancy, and barriers and enablers to reducing prenatal SHS exposure. Interventions need to empower pregnant women to feel confident in asking people not to smoke around them, focus on acquiring negotiation skills, raise awareness of actual exposure, and increase self-efficacy to use effective SHS reduction strategies. Interventions should be inclusive of all family members who smoke. These findings will inform the development of a digital intervention. Digital interventions have the potential for high reach among socially disadvantaged populations while allowing the tailoring of individualized messaging to the pregnant woman and her partner.
Herpesvirus Antibodies Are Correlated With Greater Expression of p16 in the T Cells of Humans
Authors: Noppert Grace , Wragg Kathleen , Li Chihua , Duchowny Kate , Mody Lona , Aiello Allison E , Nyquist Linda , O’Brien Martin , Yung Raymond , Goldstein Daniel
Published: December 2024

Background

There is an increasing awareness that aging of the immune system, or immunosenescence, is a key biological process underlying many of the hallmark diseases of aging and age-related decline broadly. While immunosenescence can be in part due to normal age-related changes in the immune system, emerging evidence posits that viral infections may be biological stressors of the immune system that accelerate the pace of immunosenescence

Methods

We used a convenience sample of 42 individuals aged 65 years and older to examine correlations between antiviral immunoglobulin G (IgG) levels for 4 human herpesviruses (cytomegalovirus [CMV], herpes simplex virus [types 1 and 2], and Epstein-Barr virus) and multiple indicators of T-cell immunosenescence.

Results

We found that most of the sample (n = 33) was antiviral IgG positive for 2 or more of the 4 herpesvirus infections. We also examined correlations between both the total number of viruses for which an individual had antiviral IgG and each individual virus and multiple indicators of T-cell immunosenescence, particularly p16 expression. The strongest correlations were observed between the total number of viruses for which an individual had detectable antiviral IgG and p16 mean fluorescent intensity (MFI) among CD27-CD28-CD57+ CD4+ cells (r = 0.60; P < .001) and between anti-CMV IgG and p16 MFI of CD27-CD57+ CD4+ cells (r = 0.59; P < .001).

Conclusions

Broadly, our findings offer compelling preliminary evidence for future investigations to incorporate multiple indicators of persistent viral infections and a more comprehensive set of markers of T-cell immunosenescence in population-based studies of aging.
Sepsis in Northern Tanzania: A Prospective Observational Study of Clinical Characteristics, Management, and Outcomes for Adolescents and Adults With Sepsis
Authors: Bonnewell John P , Crump John A , Egger Joseph R , Sakita Francis M , Hertz Julian T , Kilonzo Kajiru G , Maro Venance P , Rubach Matthew P
Published: December 2024

Background

Despite a high burden of sepsis in Sub-Saharan Africa, clinical data for adolescent and adult sepsis in this setting are limited. We sought to describe clinical characteristics, management, and outcomes in adolescents and adults with sepsis in northern Tanzania. We also assessed for clinical associations with in-hospital mortality.

Methods

We conducted a prospective observational cohort study at Kilimanjaro Christian Medical Centre in Moshi, Tanzania, 2019–2020. Data were collected on demographics, clinical characteristics, and management primarily from hours 0–6 after arrival at the emergency department. We calculated bivariable risk ratios (RRs) for associations between demographic and clinical factors and in-hospital death. A multivariable-adjusted analysis was performed for associations between antimicrobial and intravenous fluid administration and in-hospital death.

Results

Of 86 participants with sepsis, 25 (29.1%) died in the hospital. Baseline characteristics associated with in-hospital mortality included inability to drink unassisted (RR, 3.15; 95% CI, 1.58–6.30), altered mentation (RR, 3.94; 95% CI, 2.12–7.33), quick Sequential Organ Failure Assessment (qSOFA) score ≥2 (RR, 2.86; 95% CI, 1.42–5.72), and Universal Vital Assessment score ≥5 (RR, 6.33; 95% CI, 2.36–17.02). Twenty-nine (33.7%) received an antimicrobial by hour 6. HIV antibody testing was performed for 4 (4.7%) participants by hour 6. On multivariable analysis, neither antimicrobial administration nor intravenous fluids >1L by hour 6 was associated with in-hospital mortality.

Conclusions

Sepsis at our center in northern Tanzania carried a high risk of in-hospital mortality. Further research is needed to establish the highest-yield interventions suited to the unique characteristics of sepsis in Sub-Saharan Africa.
Clinicopathological and prognostic significance of HER2-low expression in advanced gastric cancer: a retrospective observational study
Authors: Narita Yukiya , Mizuno Taro , Ishizuka Yasunobu , Sakakida Tomoki , Masuishi Toshiki , Taniguchi Hiroya , Kadowaki Shigenori , Honda Kazunori , Ando Masashi , Tajika Masahiro , Takahari Daisuke , Muro Kei
Published: December 2024

Purpose

Human epidermal growth factor receptor 2 (HER2) status is a critical biomarker in advanced gastric cancer (AGC). While the role of HER2-positive tumors in guiding targeted therapies is well-established, the clinical implications of HER2-low expression, defined as immunohistochemistry (IHC) 1+ or IHC 2+/in situ hybridization-negative (ISH-negative), remain undetermined. The aim of this study was to investigate the prognostic significance and clinicopathological features of HER2-low AGC.

Patients and methods

This retrospective analysis involved patients with AGC treated with first-line fluoropyrimidine and platinum-based chemotherapy from 2011 to 2020. Patients were categorized into HER2-zero (HER2 IHC 0), HER2-low (IHC 1+ or 2+/ISH-negative), and HER2-positive (IHC 2+/ISH-positive or 3+) groups.

Results

Among 548 patients analyzed, 33.0%, 45.1%, and 21.8% were classified as HER2-zero, HER2-low, and HER2-positive, respectively. The proportions of male patients, intestinal-type histology, esophagogastric junction/cardia involvement, metastatic disease status, ≥2 metastatic sites, liver metastasis, lymph node metastasis, and high serum carcinoembryonic antigen levels were gradually elevated in the HER2-zero, HER2-low, and HER2-positive groups. Overall survival (median) was 13.8, 13.6, and 23.0 months, respectively, with a non-significant trend favoring HER2-positive over HER2-low (adjusted hazard ratio: 0.80; P = .0672). A delayed separation of Kaplan-Meier curves for overall survival between the HER2-zero and HER2-low groups was observed, without reaching statistical significance (adjusted hazard ratio: 1.12; P = .2568).

Conclusion

Patients with HER2-low status exhibited intermediate and specific clinicopathological features within the HER2-negative category. In terms of prognosis, HER2-low patients showed a worsening trend compared with HER2-positive patients. This evidence implies that HER2-low status represents a distinct clinical subset, bridging the gap between the HER2-zero and HER2-positive profiles.
Breeding Ammospiza nelsoni (Nelson’s Sparrow) exploits both saltmarsh and hayfields in northern habitats
Authors: Owen Kiirsti C , McLellan Nic R , Mallory Mark L , Nocera Joseph J
Published: December 2024

Ammospiza nelsoni subvirgata (Acadian subspecies of Nelson’s Sparrow) breeds in saltmarsh from northern Massachusetts to New Brunswick and eastern Quebec. In the Canadian Maritimes, this subspecies also successfully breeds in diked agricultural lands (i.e., “dikeland”) that were originally created by Acadian settlers in the 1600s. Little is known about the reasons for or consequences of using dikeland for breeding. To fill this knowledge gap, we tracked male and female sparrows, and monitored nest fates in natural saltmarsh and human-made dikeland habitats. We collected fecal samples from adults and nestlings to examine which habitat type they were foraging in, and we also quantified vegetative cover. We hypothesized that flood risk in saltmarsh played an important role in the decision of A. n. subvirgata to nest in dikeland given that the saltmarsh is regularly inundated with tidal water. Based on nest monitoring, we estimated higher overall nest success in dikeland than saltmarsh. Fecal sample analysis showed distinct differences in diet between individuals using dikeland compared with saltmarsh. We also observed differences in vegetation. These results suggest that A. n. subvirgata are able to take advantage of readily available human-made habitats for breeding. With rising sea levels and increased storm events threatening coastal habitats, it is important to understand whether coastal-breeding birds can adapt to changes and what trade-offs exist for individuals who shift to alternative habitats.
Post-flooding blooms of the non-indigenous freshwater jellyfish Craspedacusta sowerbii Lankester, 1880 in Kollam District of Kerala, India
Authors: Sreeram Miriam Paul , Prasad Reshma , Sreekumar Kaippaparambil Manikandan , Raju Aju Kallumpurathu , Augustina Treasa Areeparambil Xavier , Lüskow Florian , Saravanan Raju
Published: December 2024

Cnidarian jellyfish are common components of marine food webs, though a small number of species also thrive in freshwaters. Freshwater jellyfish (class Hydrozoa) are not uncommon in tropical and subtropical India. Several genera, each with few (<10) species, are represented. The non-indigenous Peach Blossom Jellyfish Craspedacusta sowerbii has, however, only been sighted thrice in India in the past; twice (2009 and 2016) in Kerala State, southwest India. We report on a mass occurrence of C. sowerbii in a small freshwater water body (Chirakkal pond, Karurkadavu village, Karunagapalli, Kollam District) following a major flood event in August 2018. We provide notes on environmental conditions present and the jellyfish bloom characteristics. This report establishes the presence of the invasive species in the water bodies of Kerala and its post-flooding, adding it to the 32 already reported aquatic alien species in the state. While the fate of the herein-reported C. sowerbii population explosion in Kerala State is not entirely known, we call for more regional awareness and research attention, including community involvement.
All together now: A mixed-planting experiment reveals adaptive drought tolerance in seedlings of 10 Eucalyptus species
Authors: Blackman Chris J , Halliwell Ben , Brodribb Tim J
Published: December 2024

The negative impacts of drought on plant productivity and survival in natural and crop systems are increasing with global heating, yet our capacity to identify species capable of surviving drought remains limited. Here, we tested the use of a mixed-planting approach for assessing differences in seedling drought tolerance. To homogenize dehydration rates, we grew seedlings of 10 species of Eucalyptus together in trays where roots of all individuals were overlapping in a common loam soil. These seedling combinations were dried down under cool and warm temperature conditions, and seedling responses were quantified from measurements of chlorophyll fluorescence (Fv/Fm). The day of drought (T) associated with an 88% decline in Fv/Fm (TF88) varied significantly among species and was unrelated to seedling size. No significant differences in water potentials were detected among seedlings dehydrated under warm conditions prior to leaf wilt. The rank-order of species TF88 was consistent under both temperature treatments. Under cool conditions, seedling TF88 increased with decreasing cavitation vulnerability measured on adult foliage. Under both treatments, a quadratic function best fit the relationship between seedling TF88 and sampling site mean annual precipitation. These results provide evidence for adaptive selection of seedling drought tolerance. Our findings highlight the use of mixed-planting experiments for comparing seedling drought tolerance with applications for improving plant breeding and conservation outcomes.
Referring without individuating the referent
Authors: Shahmoradi Ayoob
Published: December 2024

A theory of reference attributed to Frege, Russell, and others holds that referring to an object requires the ability to uniquely individuate it. According to a famous story told around campfires on winter nights, a group of young revolutionaries, led by Kripke and Donnellan, was destined to tear down the Frege–Russell edifice of reference—and indeed, they did. Reflecting the spirit of the 60s and 70s, this makes for a compelling tale. However, the truth is that what these young revolutionaries actually did was to merely suggest a type of reference largely ignored by others. The norms of success for this type of reference, constrained by its specific profile, cannot be generalized to all reference. Moreover, it presupposes a more fundamental kind of reference that lacks this distinctive profile.
Physical Therapist Perspectives on the Use of Telehealth with First Nations Peoples in Canada: A Qualitative Study
Authors: Moecke Débora Petry , Holyk Travis , Maddocks Stacy , Campbell Kristin L , Ho Kendall , Camp Pat G
Published: December 2024

Objective

This study aims to explore physical therapists’ perspectives on providing physical therapy to First Nations peoples in Canada via telehealth, specifically to understand 1) their perspectives on the feasibility of telehealth as a medium for health care delivery and 2) their experiences building trusting therapeutic relationships via telehealth care.

Methods

This study included 13 physical therapists who provided clinical care via telehealth for First Nations individuals in northern British Columbia in the past 3 years, and 7 master of physical therapy students undergoing or who completed their Indigenous Health clinical placement in the past 3 years and utilized telehealth. In-depth semi-structured interviews were conducted. Interview questions explored: telehealth usage and acceptance, experiences with telehealth, and overall recommendations for telehealth. Audio recordings were transcribed, and reflexive thematic analysis was conducted.

Results

Three overarching themes were identified: “Telehealth can make a huge difference, but it is widely underutilized;” “Telehealth is a little bit less personal and in-depth;” and “There is a time and place for telehealth.”

Conclusion

Telehealth shows promise in the delivery of physical therapist services to First Nations communities in Canada, enhancing accessibility, offering flexible scheduling options, and optimizing therapist time efficiency. However, successful implementation in these communities is contingent upon addressing several challenges, including building trusting therapeutic relationships. Technological glitches, the absence of physical interaction, and a history of trauma may hinder the development of the therapeutic relationship in telehealth encounters. To mitigate these challenges, cultural safety training, initial in-person appointments, community familiarity, and in-person support from a caregiver or other health care provider may play pivotal roles.

Impact

This study not only sheds light on the underutilization of telehealth but also underscores its potential to significantly improve the accessibility and efficiency of physical therapist services to First Nations peoples in Canada. The findings emphasize the nuanced dynamics of therapeutic relationships in telehealth, offering critical insights for the integration of culturally sensitive practices. Addressing the challenges pinpointed can enhance the quality of telehealth care for First Nations individuals, promote more equitable healthcare delivery, and foster positive health outcomes.
Putting Quantitative Models to the Test: An Application to the U.S.-China Trade War
Authors: Adão Rodrigo , Costinot Arnaud , Donaldson Dave
Published: December 2024

The primary motivation behind quantitative work in international trade and many other fields is to shed light on the economic consequences of policy changes and other shocks. To help assess and potentially strengthen the credibility of such quantitative predictions, we introduce an IV-based goodness-of-fit measure that provides the basis for testing causal predictions in arbitrary general equilibrium environments as well as for estimating the average misspecification in these predictions. As an illustration of how to use the measure in practice, we revisit the welfare consequences of the U.S.-China trade war predicted by Fajgelbaum et al. (2020).
A Neutral Isotropic Elastic Ellipsoidal Inhomogeneity with a Spring-Type Imperfect Interface
Authors: Wang Xu , Schiavone Peter
Published: December 2024

We study the design of an imperfectly bonded neutral isotropic elastic ellipsoidal inhomogeneity that does not disturb the prescribed uniform normal stresses in an isotropic elastic matrix. The imperfect inhomogeneity-matrix interface is modeled by a spring-type imperfect interface characterized by a single imperfect interface function. The same degree of interface imperfection is realized in both the normal and tangential directions. The two loading parameters and the imperfect interface function are determined by solving a resulting cubic equation for each one of the three types of elastic constants of the composite. All three roots of the cubic equation are permissible provided that the Young’s modulus (for the first two types) or the Poisson’s ratio (for the third type) of the inhomogeneity is higher or lower than that corresponding to the matrix. The design of a neutral superellipsoidal or paraboloidal elastic inhomogeneity with another kind of spring-type interface that does not sustain shear traction under a prescribed uniform hydrostatic stress field in the matrix is also achieved.
A classifier-based approach to multiclass anomaly detection for astronomical transients
Authors: Gupta Rithwik , Muthukrishna Daniel , Lochner Michelle
Published: December 2024

Automating real-time anomaly detection is essential for identifying rare transients, with modern survey telescopes generating tens of thousands of alerts per night, and future telescopes, such as the Vera C. Rubin Observatory, projected to increase this number dramatically. Currently, most anomaly detection algorithms for astronomical transients rely either on hand-crafted features extracted from light curves or on features generated through unsupervised representation learning, coupled with standard anomaly detection algorithms. In this work, we introduce an alternative approach: using the penultimate layer of a neural network classifier as the latent space for anomaly detection. We then propose a novel method, Multi-Class Isolation Forests, which trains separate isolation forests for each class to derive an anomaly score for a light curve from its latent space representation. This approach significantly outperforms a standard isolation forest. We also use a simpler input method for real-time transient classifiers which circumvents the need for interpolation and helps the neural network handle irregular sampling and model inter-passband relationships. Our anomaly detection pipeline identifies rare classes including kilonovae, pair-instability supernovae, and intermediate luminosity transients shortly after trigger on simulated Zwicky Transient Facility light curves. Using a sample of our simulations matching the population of anomalies expected in nature (54 anomalies and 12 040 common transients), our method discovered $41\pm 3$ anomalies ($\sim 75~{{\rm per\ cent}}$ recall) after following up the top 2000 ($\sim 15~{{\rm per\ cent}}$) ranked transients. Our novel method shows that classifiers can be effectively repurposed for real-time anomaly detection.
Optimal Pricing of a New Utility Service: The Case of Piped Water in Vietnam
Authors: Do Quy-Toan , Jacoby Hanan G
Published: December 2024

As utility services expand throughout the developing world, providers must grapple with how to set prices to recover average costs. Data from a multiyear randomised pricing experiment among nearly 1,500 recently connected piped water customers in Vietnam reveal month-to-month demand persistence. Based on structural demand estimation, we document how endogenous preferences, if unaccounted for, can lead to low take-up and thereby threaten the financial viability of the new water utility. We also show that such demand persistence calls for pricing schemes that defer lump-sum payment, effectively allowing future consumers to subsidise their present selves.
Increased risk of malignancy and osteoporosis in primary Sjögren’s syndrome with thyroid diseases: potential implication from T cells
Authors: Cui Xiaomeng , Li Jun , Sang Yizhen , Liu Wei , Lu Yikang , Li Wei , Ma Li , Liu Xinying
Published: December 2024

Objectives

To evaluate the impact of thyroid diseases (TDs) on the comorbidities incidence and immune system of patients with primary SS (pSS).

Methods

A total of 329 patients diagnosed with pSS who were admitted between January 2018 and September 2023 were evaluated. The patients were divided into two groups: those with and without TD. Clinical data at the onset of SS were recorded. Kaplan–Meier method and Cox proportional hazards model were utilized for survival analysis. Flow cytometry and immunofluorescence measurements were used to analyse the lymphocyte subtypes.

Results

Of the 329 patients, 109 had TD. The most common types of TD were thyroid nodules (40.4%) and autoimmune thyroid diseases (AITDs) (28.4%). Patients with TD exhibited a significantly elevated incidence risk of malignancy (14.7% vs. 6.4%, P = 0.01) and osteoporosis (OP) (23.9% vs. 14.1%, P = 0.03). TD comorbidity was an independent risk factor of malignancy (HR 4.7, 95% CI 1.1–19.3, P = 0.03) and OP (HR 3.7, 95% CI 1.3–10.2, P = 0.01). Patients with SS and TD exhibited a higher ratio of programmed death-1 (PD1) + subsets of total CD3+ T cells, Th and Tc cells (all P = 0.03), as well as a lower ratio of unswitched memory B cells (P = 0.01) in peripheral blood. The ratio of PD1+ subsets of Th cells in salivary glands also exhibited a significantly increase in these patients compared with those without TD (P = 0.03) and the controls (P < 0.01).

Conclusion

The incidence risk of malignancy and OP was significantly elevated in pSS patients with TD. The significant elevated proportions of PD1+ T cells may influence the occurrence of this process.
Efficacy and safety of guselkumab in patients with active lupus nephritis: results from a phase 2, randomized, placebo-controlled study
Authors: Anders Hans-Joachim , Chan Tak Mao , Sanchez-Guerrero Jorge , Wofsy David , Bensley Karen , Kim Lilianne , Lo Kim Hung , Shu Cathye , Shao Jie , Karyekar Chetan S , Diamond Betty
Published: December 2024

Objective

Evaluate the efficacy and safety of guselkumab, an IL-23p19-subunit inhibitor, in a phase 2, multicentre, randomized, double-blind, placebo-controlled study of patients with active LN.

Methods

Adults (18–75 years) with active LN [Class III–IV proliferative nephritis (kidney biopsy) and urine protein-to-creatinine ratio (UPCR) of ≥1 mg/mg despite standard-of-care therapy] were randomized (1:1; planned sample = 60) to receive i.v. infusions of guselkumab 400 mg or placebo at weeks 0, 4 and 8, then s.c. injections (guselkumab 200 mg or placebo) at week 12 and every 4 weeks through week 48 in addition to their background therapy. The primary endpoint was achievement of ≥50% decrease in proteinuria from baseline at week 24. Major secondary endpoints (week 24) were achievement of complete renal response (CRR), sustained reduction in steroid dose (≤10 mg/day prednisone/equivalent) from weeks 16–24, UPCR <0.5 mg/mg; <0.75 mg/mg, time to achieving CRR, and time to treatment failure. Safety was assessed through the end of the study.

Results

Following enrolment challenges (COVID-19 pandemic; Ukraine/Russia crisis), the sponsor terminated the study early; 33 participants were randomized (placebo, n = 16; guselkumab, n = 17). At week 24, 56.3% (9/16) in the placebo group and 35.3% (6/17) in the guselkumab group achieved the primary endpoint. No apparent differences were observed in the secondary endpoints. Through end-of-study, 75% of placebo patients and 71% of guselkumab patients reported ≥1 adverse event; most were of mild-to-moderate severity.

Conclusion

Guselkumab+background therapy did not demonstrate superior reduction in proteinuria vs placebo+background therapy in this small cohort of patients with active LN. Safety results were consistent with the known safety profile of guselkumab.

Trial registration

ClinicalTrials.gov: NCT04376827.
Development and internal–external cross-validation of a patient-reported definition for acute calcium pyrophosphate crystal arthritis
Authors: Cipolletta Edoardo , Rozza Davide , Andres Mariano , Ottaviani Sébastien , Pascart Tristan , Calvo-Aranda Enrique , Chiarvetto Peralta Maria Victoria , Muto Pietro , Calabuig Irene , Gómez-Sabater Silvia , Caño Rocío , Léger Bastien , Pacaud Aurore , Moscioni Erica , Bruno Caterina , Caira Virginia , Gómez-González Claudia , Rosa Javier Eduardo , Nakafero Georgina , Filippucci Emilio , Abhishek Abhishek
Published: December 2024

Objective

To develop and validate a patient-reported definition of acute calcium pyrophosphate (CPP) crystal arthritis in people with crystal-proven CPP deposition (CPPD) disease.

Methods

Consecutive patients with crystal-proven CPPD disease from seven centres across four countries were enrolled in a cross-sectional study. In each centre, patient-reported outcomes on the features of acute CPP crystal arthritis were collected. The expert opinion of an independent rheumatologist was the reference standard. We developed definitions based on multivariable logistic regression model with backward selection of predictors and classification and regression tree (CART) approaches.

Results

Two hundred and forty-six patients [mean age 73.2 years (s.d. 10.7), 65.9% female] were enrolled. At the time of the assessment, acute CPP crystal arthritis was diagnosed in 96/246 (39.0%) participants.

Patient-reported joint warmth, patient-reported joint swelling, time from pain onset to peak, and self-reported acute CPP crystal inflammatory arthritis were included in the multivariable logistic model. This model had good discrimination (optimism-adjusted c-index: 0.92; 95% CI: 0.89, 0.95) and calibration (optimism-adjusted calibration slope: 0.95; 95% CI: 0.71, 1.19; optimism-adjusted calibration-in-the-large: 0.005; 95% CI: −0.37, 0.37) in the internal validation. Probability threshold ≥0.53 had sensitivity of 0.83 (95% CI: 0.74, 0.90) and specificity of 0.86 (95% CI: 0.79, 0.91). Performances were similar in the internal–external cross-validation. The CART identified patient-reported acute CPP crystal inflammatory arthritis, followed by joint swelling and joint warmth as the most informative variables for ascertaining acute CPP crystal arthritis [sensitivity 0.83 (95% CI: 0.72, 0.91) and specificity 0.83 (95% CI: 0.74, 0.90)].

Conclusion

We developed and initially validated easy-to-use patient-reported definitions for acute CPP crystal arthritis for use in clinical trials and observational research in CPPD.
Integrating carotid Doppler, greyscale US, and aortic oscillometry to evaluate macroangiopathy in myositides: the MYOCARD cohort
Authors: Triantafyllias Konstantinos , Gauch Svea , Bertsias George , Boumpas Dimitrios , Hasseli Rebecca , Cavagna Lorenzo , Bergner Raoul , Schepers Markus , Schwarting Andreas
Published: December 2024

Objectives

To evaluate the combination of novel colour Doppler US (CDUS), greyscale US (GSUS), and oscillometric indices of macroangiopathy in patients with idiopathic inflammatory myopathies (IIM). Second, to explore the associations between these imaging markers and both patient-related and disease-related characteristics, as well as traditional cardiovascular (CV) risk factors.

Methods

We conducted CDUS to evaluate arterial compliance markers, specifically the resistance (RI) and pulsatility (PI) indices, both in the common (CCA) and internal carotid arteries (ICA) of patients with IIM and healthy controls. Additionally, we performed GSUS examinations to measure carotid intima-media thickness (cIMT), identify plaques, and quantify cumulative carotid calcification surface. Oscillometric assessments determined aortic stiffness using carotid-femoral pulse wave velocity (cfPWV).

Results

We recruited 82 IIM patients and 88 healthy controls. Patients showed significantly higher cIMT (Padj = 0.032), CCA-RI (Padj = 0.015), CCA-PI (Padj = 0.013), ICA-RI (Padj = 0.012), and ICA-PI (Padj = 0.039), compared with controls. RI and PI of CCA and ICA were higher in patients with lower lung function vital capacity, respectively (all Ps < 0.05). cfPWV correlated positively with traditional CV risk factors including age (ρ = 0.546, P < 0.001), mean arterial pressure (ρ = 0.331, P = 0.003), diabetes (P = 0.007), and hyperlipidaemia (P = 0.032), and associated negatively with lung carbon monoxide (CO) diffusion (ρ = −0.329, P = 0.031).

Conclusion

In one of the largest CV surrogate marker studies in IIM, patients exhibited increased carotid pulsatility, resistance, and atherosclerosis compared with controls. Lower lung function parameters predicted aortic stiffness and Doppler indices, suggesting a possible link between lung involvement and increased CV risk. Angiopathy markers may reveal significant vascular abnormalities in IIM patients, enhancing CV screening and risk classification.
Drug-induced liver injury related to avacopan therapy
Authors: Mori Kentaro , Shirai Tsuyoshi , Mutoh Tomoyuki , Inoue Jun , Fujishima Fumiyoshi , Kubo Satsuki , Watanabe Hirofumi , Sato Satoko , Narita Mamoru , Hoshi Yosuke , Sato Hiroko , Fujii Hiroshi
Published: December 2024

Objectives

The efficacy of avacopan as remission induction therapy for Anti-Neutrophil Cytoplasmic Autoantibody (ANCA)-associated vasculitis (AAV) is well-established. However, concerns regarding liver injury post-avacopan treatment remain, especially in Japan. Therefore, this study aimed to investigate drug-induced liver injury (DILI) associated with avacopan treatment.

Methods

This study included 22 patients with AAV who were treated with avacopan at multiple centres in Japan between September 2021 and March 2024. DILI was assessed by the Japanese version of a revised electronic causality assessment method (RECAM-J 2023).

Results

Among the 22 patients treated with avacopan, DILI was observed in nine cases (40.9%): six with microscopic polyangiitis and three with granulomatosis with polyangiitis. Severe DILI with elevated total bilirubin (T-Bil) was observed in four of the nine patients (44.4%), a few weeks after the initiation of avacopan therapy. Eight of the nine patients (88.9%) with DILI improved after discontinuation of avacopan and other medications, and one patient developed vanishing bile duct syndrome (VBDS) leading to death. Avacopan-induced DILI was classified into three patterns: 1, short-term injury without T-Bil elevation; 2, transient cholestatic liver injury with T-Bil elevation; 3, decompensated liver injury with marked T-Bil elevation (VBDS). The risk factors for severe DILI with T-Bil elevation in Japanese patients included older age, lower body mass index and early onset DILI following the initiation of avacopan treatment.

Conclusion

Avacopan-induced DILI is relatively common in Japan and could be lethal. Frequent laboratory follow-ups should be considered, especially for elderly and low-body-weight patients.
Enhancing 3D-printed chocolate drug delivery: the role of soy lecithin in improving formulation printability and consistency
Authors: Lesutan Vlad-Nicolae , Milliken Rachel Louise , Browne Amber , Ferguson Tommy , Lamprou Dimitrios A
Published: December 2024

Objectives

This study explores the potential of extrusion-based 3D printing to improve medication adherence by developing chocolate-based oral dosage forms incorporating active pharmaceutical ingredients such as paracetamol and ibuprofen while using soy lecithin as an emulsifier to enhance the flow properties of the chocolate formulation, enabling consistent and reliable 3D printing of the dosage forms.

Methods

Extrusion-based 3D printing was used to obtain drug-loaded solid oral dosage forms. The formulation components as well as the printing design and conditions were optimized, to enhance the appearance and patient acceptability of the final products. Techniques such as spectroscopy, thermal analysis, rheology, mechanical analysis, and in-vitro dissolution were employed to assess the physicochemical properties of these formulations.

Key findings

Soy lecithin was essential in obtaining robust and consistent dosage forms. The formulations showed good physicochemical stability of the components and demonstrated consistent drug release.

Conclusions

The findings suggest that extrusion-based 3D printing, with the aid of emulsifiers such as soy lecithin, is a viable method for producing personalized, chocolate-based drug delivery systems, potentially improving adherence through customizable dosage forms. Further research could enhance understanding of factors such as particle size, crystallinity, and the impact of chewing on drug release to optimize therapeutic outcomes.
Association Between Peptide Antigen-Related Antibody Levels and the Short- and Long-Term Efficacy of Antipsychotic Treatment in Drug-Naïve First-Episode Schizophrenia Patients
Authors: Zheng Yue , Du Jian , Wang Mingqia , Zhou Enpeng , Zhou Qi , Ji Yunfei , Huang Bingjie , Guo Xiaodong , Gao Tianqi , Hu Wanheng , Yin Xiaolin , Wang Xianghe , Pu Chengcheng , Yu Xin
Published: December 2024

Objective

This study investigated the relationships between baseline peptide antigen-related IgG levels and 8-week antipsychotic drug (APD) treatment response rates and one-year treatment outcomes, as well as the relationships between changes in peptide antigen-related IgG levels and one-year treatment outcomes, in first-episode schizophrenia (FES) patients.

Methods

Sixteen peptide antigen-related IgGs from proteins encoded by schizophrenia-related genes were selected on the basis of several selection criteria from a 2022 genome-wide association study. Novel peptide antigen-related IgG levels were measured in drug-naïve FES patients at baseline (n = 155) and in plasma samples from 60 healthy controls (HCs). At the one-year follow-up, 57 patients completed both symptom and autoantibody assessments. Statistical analyses included t tests, Pearson correlation analysis, linear regression analysis, linear mixed-effects models, and simple slope analysis.

Results

Anti-MOB4 IgG and anti-PDIA3 IgG levels were significantly lower in drug-naïve FES patients compared to HCs and showed a negative correlation with baseline excitement factor scores. Baseline anti-EMB IgG levels were associated with the 8-week treatment response, whereas anti-MAD1L1 IgG levels were correlated with one-year outcomes in drug-naïve FES patients. The one-year trajectory of changes in anti-FURIN IgG, anti-MAPK3 IgG, and anti-ACTR1B IgG levels was related to remission.

Conclusion

This study revealed that patients with schizophrenia had autoimmune abnormalities, with different peptide antigen-related IgG being associated with short-term or long-term treatment efficacy, and that these antibody levels were regulated by APDs.
Revisiting the Defeatist Performance Belief Scale in Adults With Schizophrenia and Youth at Clinical High-Risk for Psychosis: A Comprehensive Psychometric Analysis
Authors: Luther Lauren , Ahmed Anthony O , Grant Paul M , Granholm Eric , Gold James M , Williams Trevor F , Pratt Danielle , Holden Jason , Walker Elaine F , Arnold Lauren , Ellman Lauren M , Mittal Vijay A , Zinbarg Richard , Silverstein Steve M , Corlett Philip R , Powers Albert R , Woods Scott W , Waltz James A , Schiffman Jason , Strauss Gregory P
Published: December 2024

Background and Hypothesis

In accordance with the Cognitive Model of Negative Symptoms, defeatist performance beliefs (DPBs) are an important psychosocial mechanism of negative symptoms in schizophrenia-spectrum groups. DPBs are also mediators of negative symptom improvement in clinical trials. Despite the clinical significance of DPBs and their inclusion as a mechanism of change measure in clinical trials, the psychometric properties of the DPB scale have not been examined in any schizophrenia-spectrum group.

Study Design

This study evaluated the factor structure, reliability, and validity of the DPB scale in 943 schizophrenia and 250 clinical high-risk for psychosis (CHR) participants from multiple US sites. Confirmatory factor analyses tested competing factor structures: a unidimensional model—consistent with how DPBs are currently assessed—and multifactorial models with up to 4 factors identified with exploratory factor analyses.

Study Results

Models with 3 and 4 factors provided superior fit compared to the unidimensional model, with an advantage for the 3-factor model. The 3-factor model, consisting of Overvaluing Success, Overvaluing Failure, and Overvaluing Social Evaluation factors, demonstrated good replicability, temporal stability, and measurement invariance in schizophrenia and CHR samples. Convergent validity was demonstrated via significant correlations with negative symptoms and functioning, but limited associations were present with neurocognition. Discriminant validity was supported by low correlations with positive symptoms.

Conclusions

Findings support the validity and reliability of the 3-factor structure of the DPB scale across phases of psychosis. Use of a 3-factor structure may clarify the most critical DPB targets for negative symptom treatment and early prevention and intervention.
O002 Sleepy teens and the use of screens: A repeated measures analysis examining the relationship between pre-bedtime screen use and sleep
Authors: Wickham S , Brosnan B , Haszard J , Meredith-Jones K , Galland B , Taylor R
Published: December 2024

Aims

Pre-bedtime screen use among adolescents is highly prevalent and fast-paced, often involving multiple devices, and frequent switching between activities, which is presumed to be harmful to sleep. The aim of this study was to determine how objectively-measured evening screen time influenced sleep in young adolescents.

Methods

BED was a repeated-measures observational study in 85 healthy adolescents (11-14.9 years). Objective screen time data were captured over four non-consecutive nights using video cameras from two hours before bedtime until the adolescent attempted sleep (shuteye time) and coded using a reliable protocol (κ ≥ 0.8). Sleep outcomes (sleep timing, total sleep time, and WASO) were measured objectively via wrist-worn AX3 accelerometers. Screen use was related to sleep on a night-by-night basis using a mixed-effects regression model, which considered participant as a random effect and adjusted for weekends.

Results

Screen time in the two hours before bed had little effect on sleep that night. However, once in bed, screen time delayed sleep onset by 35 (95% CI: 20, 50) minutes compared to nights without screen use. Interactive screen use reduced TST more than passive screen use (9 compared with 4 minutes for every 10 minutes of use, but time since last screen use did not impact any measure of sleep health examined.

Conclusion

Improved methodology shows that screen time may impair sleep once in bed, especially if interactive. Current sleep hygiene recommendations to restrict all screen time before bed seem neither achievable nor appropriate within this age group.