bluuebunny/crossref_metadata_2025_split huggingface dataset:
Robust data integration from multiple external sources for generalized linear models with binary outcomes
Authors: Choi Kyuseong , Taylor Jeremy M G , Han Peisong 
Published: February 2024

ABSTRACTWe aim to estimate parameters in a generalized linear model (GLM) for a binary outcome when, in addition to the raw data from the internal study, more than 1 external study provides summary information in the form of parameter estimates from fitting GLMs with varying subsets of the internal study covariates. We propose an adaptive penalization method that exploits the external summary information and gains efficiency for estimation, and that is both robust and computationally efficient. The robust property comes from exploiting the relationship between parameters of a GLM and parameters of a GLM with omitted covariates and from downweighting external summary information that is less compatible with the internal data through a penalization. The computational burden associated with searching for the optimal tuning parameter for the penalization is reduced by using adaptive weights and by using an information criterion when searching for the optimal tuning parameter. Simulation studies show that the proposed estimator is robust against various types of population distribution heterogeneity and also gains efficiency compared to direct maximum likelihood estimation. The method is applied to improve a logistic regression model that predicts high-grade prostate cancer making use of parameter estimates from 2 external models.
A generalized phase 1-2-3 design integrating dose optimization with confirmatory treatment comparison
Authors: Zang Yong , Thall Peter F , Yuan Ying 
Published: February 2024

ABSTRACT
A generalized phase 1-2-3 design, Gen 1-2-3, that includes all phases of clinical treatment evaluation is proposed. The design extends and modifies the design of Chapple and Thall (2019), denoted by CT. Both designs begin with a phase 1-2 trial including dose acceptability and optimality criteria, and both select an optimal dose for phase 3. The Gen 1-2-3 design has the following key differences. In stage 1, it uses phase 1-2 criteria to identify a set of candidate doses rather than 1 dose. In stage 2, which is intermediate between phase 1-2 and phase 3, it randomizes additional patients fairly among the candidate doses and an active control treatment arm and uses survival time data from both stage 1 and stage 2 patients to select an optimal dose. It then makes a Go/No Go decision of whether or not to conduct phase 3 based on the predictive probability that the selected optimal dose will provide a specified substantive improvement in survival time over the control. A simulation study shows that the Gen 1-2-3 design has desirable operating characteristics compared to the CT design and 2 conventional designs.
Group work enhances student performance in biology: A meta-analysis
Authors: Driessen Emily P , Wilson Alan E , Hall Ian , Brewer Peyton , Odom Sara , Ramsey Sara Beth , Wood Sara , Ballen Cissy J 
Published: February 2024

Abstract
We conducted a meta-analysis to test the impacts of one active learning teaching strategy, group work, on student performance by calculating estimates across 91 studies from 53 articles. Our overall estimate indicates that the implementation of group work in biology classrooms increased student performance by 1.00 standard deviation, which we contextualized as a change greater than one letter grade. Moderator analyses revealed that this increase in performance held across all group sizes, class sizes, biology and life science majors and nonmajors, and whether the groups were assigned by the instructor. However, we did not observe increased performance in graduate level courses, in cases where group work was incorporated for only part of the course term (e.g., less than a semester or quarter) or when the group work was not graded. These results demonstrate that group work leads to impressive boosts in student performance and underscores the value of studying specific active learning strategies.
A Bayesian approach for investigating the pharmacogenetics of combination antiretroviral therapy in people with HIV
Authors: Jin Wei , Ni Yang , Spence Amanda B , Rubin Leah H , Xu Yanxun 
Published: February 2024

Summary
Combination antiretroviral therapy (ART) with at least three different drugs has become the standard of care for people with HIV (PWH) due to its exceptional effectiveness in viral suppression. However, many ART drugs have been reported to associate with neuropsychiatric adverse effects including depression, especially when certain genetic polymorphisms exist. Pharmacogenetics is an important consideration for administering combination ART as it may influence drug efficacy and increase risk for neuropsychiatric conditions. Large-scale longitudinal HIV databases provide researchers opportunities to investigate the pharmacogenetics of combination ART in a data-driven manner. However, with more than 30 FDA-approved ART drugs, the interplay between the large number of possible ART drug combinations and genetic polymorphisms imposes statistical modeling challenges. We develop a Bayesian approach to examine the longitudinal effects of combination ART and their interactions with genetic polymorphisms on depressive symptoms in PWH. The proposed method utilizes a Gaussian process with a composite kernel function to capture the longitudinal combination ART effects by directly incorporating individuals’ treatment histories, and a Bayesian classification and regression tree to account for individual heterogeneity. Through both simulation studies and an application to a dataset from the Women’s Interagency HIV Study, we demonstrate the clinical utility of the proposed approach in investigating the pharmacogenetics of combination ART and assisting physicians to make effective individualized treatment decisions that can improve health outcomes for PWH.
A multicentre randomized double-blind placebo-controlled phase III study of the efficacy and safety of xeligekimab (GR1501) in patients with moderate-to-severe plaque psoriasis
Authors: Cai Lin , Jiang Congjun , Zhang Guoqiang , Fang Hong , Wang Jinyan , Li Yumei , Xu Hui , Xiao Rong , Ding Yangfeng , Huang Kun , Zhang Chunlei , Zhang Litao , Chen Bin , Duan Xinsuo , Pan Weili , Han Guangming , Chen Rongyi , Liu Lunfei , Zhang Shoumin , Tao Juan , Pang Xiaowen , Yu Jianbin , Wang Huiping , Zhao Yi , Li Chengxin , Kang Xiaojing , Qin Lanying , Zhu Xiaofang , Su Juan , Li Shanshan , Yang Chunjun , Feng Wenli , Lei Tiechi , Jiang Shan , Fang Ruihua , Lin Mao , Lu Qianjin , Xu Chunxing , Wang Wei , Zhang Jianzhong 
Published: February 2024

Abstract

Background
Xeligekimab (GR1501) is a fully human monoclonal antibody that selectively neutralizes interleukin (IL)-17A and has shown potential efficacy in treating moderate-to-severe psoriasis in preliminary trials.

Objectives
To evaluate the efficacy and safety of xeligekimab in Chinese patients with moderate-to-severe psoriasis.

Methods
A total of 420 Chinese patients were randomized to 200 mg xeligekimab every 2 weeks (n = 281) or placebo (n = 139) for the first 12 weeks, followed by an extension of the treatment schedule to xeligekimab every 4 weeks for a further 40 weeks. Efficacy was assessed by evaluating achievement of Physician Global Assessment (PGA) 0/1 and 75%, 90% and 100% improvement in Psoriasis Area and Severity Index (PASI 75, PASI 90 and PASI 100, respectively). The safety profile was also evaluated.

Results
At week 12, PASI 75, PASI 90 and PASI 100 were achieved in 90.7%, 74.4% and 30.2% of patients in the xeligekimab group vs. 8.6%, 1.4% and 0% of patients in the placebo group, respectively. PGA 0/1 was achieved in 74.4% patients in the xeligekimab group and 3.6% of patients in the placebo group. PASI 75 and PGA 0/1 were maintained until week 52. No unexpected adverse events were recorded.

Conclusions
Xeligekimab showed high efficacy and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.
Acceptability of ‘as needed’ biologic therapy in psoriasis: insights from a multistakeholder mixed-methods study
Authors: Gleeson David , Naveed Maneeha , Moorhead Lucy , McAteer Helen , Sewell Georgia , McGuire Arlene , Weinman John , Barker Jonathan N W N , Norton Sam , Chapman Sarah C E , Smith Catherine H , Mahil Satveer K 
Published: February 2024

Abstract

Background
Biologic therapies have led to increasing numbers of patients with psoriasis who have clear or nearly clear skin. It is current practice to continue biologic therapy indefinitely in these patients, which contributes to a substantial long-term drug and healthcare burden. ‘As needed’ biologic therapy in psoriasis may address this; however, our understanding of patient and clinician perceptions of this strategy is limited.

Objectives
The aim of this mixed-methods study was to gain insight into the perspectives of both patients and clinicians regarding the acceptability of an ‘as needed’ approach to biologic therapy in psoriasis, including potential barriers and enablers to implementation in routine care.

Methods
We first conducted UK-wide online scoping surveys of patients with psoriasis and dermatology clinicians to explore their views on ‘as needed’ biologic therapy. Using topic guides informed by these survey findings, we then carried out qualitative focus groups with patients and clinicians. Themes were identified using reflexive thematic analysis.

Results
Of 67 patients and 27 clinicians completing the scoping surveys, 67% (43 of 64 patients) and 78% (21 of 27 clinicians) supported the use of ‘as needed’ biologic therapy, respectively. Respondents highlighted advantages such as a reduction in healthcare burden and greater ownership of care. Challenges included logistics of ‘as needed’ drug provision and potential risks of disease flare and drug immunogenicity. Focus groups comprised 15 patients with psoriasis [9 female patients (60%), average disease duration 32 years (range 9–64)] and 9 dermatology clinicians [8 female clinicians (89%), average dermatology experience 20 years (range 8–33)]. Both patients and clinicians felt that an ‘as needed’ treatment approach will deliver a reduction in treatment burden and present an opportunity for patient-led ownership of care. Both groups highlighted the importance of ensuring ongoing access to medication and discussing the potential impact of psoriasis recurrence. Patient preferences were influenced by their lived experiences, particularly previous difficulties with medication delivery logistics and establishing disease control. Clinician perspectives were informed by personal experience of their patients adapting their own dosing schedules. Clinicians highlighted the importance of targeted patient selection for an ‘as needed’ approach, ongoing disease monitoring, and prompt reaccess to medications upon psoriasis recurrence.

Conclusions
These data indicate that ‘as needed’ biologic therapy in psoriasis is acceptable for both patients and clinicians. Formal assessment of clinical effectiveness and cost-effectiveness is warranted to enable the real-world potential of this approach to be realized.
Clinical efficacy of motion-insensitive imaging technique with deep learning reconstruction to improve image quality in cervical spine MR imaging
Authors: Song You Seon , Lee In Sook , Hwang Moonjung , Jang Kyoungeun , Wang Xinzeng , Fung Maggie 
Published: February 2024

Abstract

Objective
To demonstrate that a T2 periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) technique using deep learning reconstruction (DLR) will provide better image quality and decrease image noise.

Methods
From December 2020 to March 2021, 35 patients examined cervical spine MRI were included in this study. Four sets of images including fast spin echo (FSE), original PROPELLER, PROPELLER DLR50%, and DLR75% were quantitatively and qualitatively reviewed. We calculated the signal-to-noise ratio (SNR) of the spinal cord and sternocleidomastoid (SCM) muscle and the contrast-to-noise ratio (CNR) of the spinal cord by applying region-of-interest at the spinal cord, SCM muscle, and background air. We evaluated image noise with regard to the spinal cord, SCM, and back muscles at each level from C2-3 to C6-7 in the 4 sets.

Results
At all disc levels, the mean SNR values for the spinal cord and SCM muscles were significantly higher in PROPELLER DLR50% and DLR75% compared to FSE and original PROPELLER images (P &lt; .0083). The mean CNR values of the spinal cord were significantly higher in PROPELLER DLR50% and DLR75% compared to FSE at the C3-4 and 4-5 levels and PROPELLER DLR75% compared to FSE at the C6-7 level (P &lt; .0083). Qualitative analysis of image noise on the spinal cord, SCM, and back muscles showed that PROPELLER DLR50% and PROPELLER DLR75% images showed a significant denoising effect compared to the FSE and original PROPELLER images.

Conclusion
The combination of PROPELLER and DLR improved image quality with a high SNR and CNR and reduced noise.

Advances in knowledge
Motion-insensitive imaging technique (PROPELLER) increased the image quality compared to conventional FSE images. PROPELLER technique with a DLR reduced image noise and improved image quality.
Differentiation of acute coronary syndrome with radiomics of pericoronary adipose tissue
Authors: Jing Mengyuan , Xi Huaze , Sun Jianqing , Zhu Hao , Deng Liangna , Han Tao , Zhang Bin , Zhang Yuting , Zhou Junlin 
Published: February 2024

Abstract

Objective
To assess the potential values of radiomics signatures of pericoronary adipose tissue (PCAT) in identifying patients with acute coronary syndrome (ACS).

Methods
In total, 149, 227, and 244 patients were clinically diagnosed with ACS, chronic coronary syndrome (CCS), and without coronary artery disease (CAD), respectively, and were retrospectively analysed and randomly divided into training and testing cohorts at a 2:1 ratio. From the PCATs of the proximal left anterior descending branch, left circumflex branch, and right coronary artery (RCA), the pericoronary fat attenuation index (FAI) value and radiomics signatures were calculated, among which features closely related to ACS were screened out. The ACS differentiation models AC1, AC2, AC3, AN1, AN2, and AN3 were constructed based on the FAI value of RCA and the final screened out first-order and texture features, respectively.

Results
The FAI values were all higher in patients with ACS than in those with CCS and no CAD (all P &lt; .05). For the identification of ACS and CCS, the area-under-the-curve (AUC) values of AC1, AC2, and AC3 were 0.92, 0.94, and 0.91 and 0.91, 0.86, and 0.88 in the training and testing cohorts, respectively. For the identification of ACS and no CAD, the AUC values of AN1, AN2, and AN3 were 0.95, 0.94, and 0.94 and 0.93, 0.87, and 0.89 in the training and testing cohorts, respectively.

Conclusions
Identification models constructed based on the radiomics signatures of PCAT are expected to be an effective tool for identifying patients with ACS.

Advances in knowledge
The radiomics signatures of PCAT and FAI values are expected to differentiate between patients with ACS, CCS and those without CAD on imaging.
Phenoconversion in pure autonomic failure: a multicentre prospective longitudinal cohort study
Authors: Millar Vernetti Patricio , Norcliffe-Kaufmann Lucy , Palma Jose-Alberto , Biaggioni Italo , Shibao Cyndya A , Peltier Amanda , Freeman Roy , Gibbons Christopher , Goldstein David S , Low Phillip A , Singer Wolfgang , Coon Elizabeth A , Miglis Mitchell G , Wenning Gregor K , Fanciulli Alessandra , Vernino Steven , Betensky Rebecca A , Kaufmann Horacio 
Published: February 2024

Abstract
We aimed to describe the clinical features of patients with pure autonomic failure (PAF) preceding phenoconversion that could be useful as predictive markers for advancing α-synuclein-associated neurodegeneration of the brain.
Patients diagnosed with PAF were evaluated at eight centres (seven US-based and one European) and enrolled in a longitudinal observational cohort study (NCT01799915). Subjects underwent detailed assessments of motor, sleep, olfactory, cognitive and autonomic function and were followed prospectively to determine whether they developed parkinsonism or dementia for up to 10 years. We identified incident cases of Parkinson's disease (PD), dementia with Lewy bodies (DLB) or multiple system atrophy (MSA) and computed hazard ratios for phenoconversion as functions of clinical features.
A total of 209 participants with PAF with a median disease duration of 6 years (IQR: 3–10) were enrolled. Of those, 149 provided follow-up information at an office or telemedicine visit. After a mean follow-up duration of 3 years, 48 (33%) participants phenoconverted (42% to PD, 35% to DLB and 23% to MSA). Faster phenoconversion from study enrolment to any diagnosis was associated with urinary and sexual dysfunction [hazard ratio (HR) 5.9, 95% confidence interval (CI): 1.6–22 and HR: 3.6, 95% CI: 1.1–12] followed by subtle motor signs (HR: 2.7, 95% CI: 1.2–6), trouble swallowing (HR 2.5, 95% CI: 1.4–4.5) and changes in speech (HR:2.4, 95% CI:1.1–4.8) at enrolment. Subjects reporting deterioration of handwriting were more likely to phenoconvert to PD (HR: 2.6, 95% CI: 1.1–5.9) and those reporting difficulty handling utensils were more likely to phenoconvert to DLB (HR: 6.8, 95% CI: 1.2–38). Patients with a younger age of PAF onset (HR: 11, 95% CI: 2.6–46), preserved olfaction (HR: 8.7, 95% CI: 1.7–45), anhidrosis (HR: 1.8, 95% CI: 1–3.1, P = 0.042) and severe urinary problems (HR 1.6, 95% CI: 1–2.5, P = 0.033) were more likely to phenoconvert to MSA. The best autonomic predictor of PD was a blunted heart rate increase during the tilt-table test (HR: 6.1, 95% CI: 1.4–26).
Patients with PAF have an estimated 12% (95% CI: 9–15%) per year annual risk following study entry of phenoconverting to a manifest CNS synucleinopathy.
Anatomo-functional basis of emotional and motor resonance elicited by facial expressions
Authors: Del Vecchio Maria , Avanzini Pietro , Gerbella Marzio , Costa Sara , Zauli Flavia Maria , d’Orio Piergiorgio , Focacci Elena , Sartori Ivana , Caruana Fausto 
Published: February 2024

Abstract
Simulation theories predict that the observation of other’s expressions modulates neural activity in the same centres controlling their production. This hypothesis has been developed by two models, postulating that the visual input is directly projected either to the motor system for action recognition (motor resonance) or to emotional/interoceptive regions for emotional contagion and social synchronization (emotional resonance). Here we investigated the role of frontal/insular regions in the processing of observed emotional expressions by combining intracranial recording, electrical stimulation and effective connectivity.
First, we intracranially recorded from prefrontal, premotor or anterior insular regions of 44 patients during the passive observation of emotional expressions, finding widespread modulations in prefrontal/insular regions (anterior cingulate cortex, anterior insula, orbitofrontal cortex and inferior frontal gyrus) and motor territories (Rolandic operculum and inferior frontal junction). Subsequently, we electrically stimulated the activated sites, finding that (i) in the anterior cingulate cortex and anterior insula, the stimulation elicited emotional/interoceptive responses, as predicted by the ‘emotional resonance model’; (ii) in the Rolandic operculum it evoked face/mouth sensorimotor responses, in line with the ‘motor resonance’ model; and (iii) all other regions were unresponsive or revealed functions unrelated to the processing of facial expressions. Finally, we traced the effective connectivity to sketch a network-level description of these regions, finding that the anterior cingulate cortex and the anterior insula are reciprocally interconnected while the Rolandic operculum is part of the parieto-frontal circuits and poorly connected with the former.
These results support the hypothesis that the pathways hypothesized by the ‘emotional resonance’ and the ‘motor resonance’ models work in parallel, differing in terms of spatio-temporal fingerprints, reactivity to electrical stimulation and connectivity patterns.
HSV-1 reactivation results in post-herpetic neuralgia by upregulating Prmt6 and inhibiting cGAS-STING
Authors: Kong Erliang , Hua Tong , Li Jian , Li Yongchang , Yang Mei , Ding Ruifeng , Wang Haowei , Wei Huawei , Feng Xudong , Han Chaofeng , Yuan Hongbin 
Published: February 2024

Abstract
Chronic varicella zoster virus (VZV) infection induced neuroinflammatory condition is the critical pathology of post-herpetic neuralgia (PHN). The immune escape mechanism of VZV remains elusive. As to mice have no VZV infection receptor, herpes simplex virus type 1 (HSV-1) infection is a well established PHN mice model.
Transcriptional expression analysis identified that the protein arginine methyltransferases 6 (Prmt6) was upregulated upon HSV-1 infection, which was further confirmed by immunofluorescence staining in spinal dorsal horn. Prmt6 deficiency decreased HSV-1-induced neuroinflammation and PHN by enhancing antiviral innate immunity and decreasing HSV-1 load in vivo and in vitro. Overexpression of Prmt6 in microglia dampened antiviral innate immunity and increased HSV-1 load. Mechanistically, Prmt6 methylated and inactivated STING, resulting in reduced phosphorylation of TANK binding kinase-1 (TBK1) and interferon regulatory factor 3 (IRF3), diminished production of type I interferon (IFN-I) and antiviral innate immunity. Furthermore, intrathecal or intraperitoneal administration of the Prmt6 inhibitor EPZ020411 decreased HSV-1-induced neuroinflammation and PHN by enhancing antiviral innate immunity and decreasing HSV-1 load.
Our findings revealed that HSV-1 escapes antiviral innate immunity and results in PHN by upregulating Prmt6 expression and inhibiting the cGAS-STING pathway, providing novel insights and a potential therapeutic target for PHN.