bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early German Positivism
Authors: Beiser Frederick C 
Published: October 2024

Abstract
This book is an attempt to recover a neglected chapter of the history of philosophy: the history of early German positivism, 1860–1914. It treats figures almost completely forgotten in the German and Anglo-American worlds: Theodor Gomperz (1832–1912), Eugen Dühring (1833–1921), Ernst Laas (1837–85), and Friedrich Jodl (1849–1914); it also examines Ernst Mach (1838–1916) and Richard Avenarius (1843–1896), who are much better known but contemporaries of these thinkers. The first four of these figures became famous, and published their major works, before the formation of the (first) Vienna Circle in 1912. Several positivist themes unite these thinkers: rejection of the synthetic a priori; opposition to pessimism; a philosophy of monism, naturalism, and historicism; and the belief that the highest good can be achieved only under the guidance of science. Positivism was thus a continuation of the Enlightenment into the 20th century. The examination of early positivism makes it necessary to question several claims made about positivism by Michael Friedman: that the positivists’ main concerns did not arise within the empiricist tradition; that the positivist rejection of the synthetic a priori arose from developments in geometry; that there is no foundationalism within positivism. Placing positivism in this broader intellectual context makes all these claims questionable. The aim throughout is to place positivism in a wider intellectual context, which goes back to the Enlightenment and the opposition to the Christian tradition.
Eugen Dühring
Authors: Beiser Frederick C 
Published: October 2024

Abstract
Dühring was the father of German positivism. His Natürliche Dialektik states many of the central themes of positivism: the unity of science; rejection of metaphysics; the defense of empiricism; the rejection of the synthetic a priori; the orientation of philosophy around the empirical sciences. Dühring was an admirer of Comte, and his major work, Cursus der Philosophie, was modeled around Comte’s Cours de philosohie positive. This chapter examines several aspects of Dühring’s philosophy: his critique of Schopenhauer’s pessimism; his naturalism and materialism; his philosophy of science; and his dispute with Friedrich Engels.
Marital Status Discrimination in India
Authors: Ghosh Arijeet , Sanyal* Diksha 
Published: October 2024

Abstract
Marital status discrimination, like race and sex, is a ground for discrimination in many jurisdictions. In India however, such a ground has neither been constitutionally nor statutorily recognized. With recent attempts by civil society to advocate for an anti-discrimination law, such a ground could, however, become a part of the legal system. This chapter identifies laws and policies across the domains of family, health, labour, welfare, and citizenship that privilege heterosexual, monogamous, married couples in India directly or indirectly. Thereafter, we attempt to analyse whether recognizing marital discrimination statutorily or constitutionally could be a potential way to challenge the discrimination experienced by non-heterosexual, non-marital couples, and single individuals. By undertaking a textual analysis of these central laws and policies, we aim to describe how marriage is entrenched in Indian legal discourse and the extent to which recognizing marital status as a ground could correct this.
Using Overlap Weights to Address Extreme Propensity Scores in Estimating Restricted Mean Counterfactual Survival Times
Authors: Cao Zhiqiang , Ghazi Lama , Mastrogiacomo Claudia , Forastiere Laura , Wilson F Perry , Li Fan 
Published: October 2024

Abstract
While inverse probability of treatment weighting (IPTW) is a commonly used approach for treatment comparisons in observational data, the resulting estimates may be subject to bias and excessively large variance under lack of overlap. By smoothly down-weighting units with extreme propensity scores, i.e., those that are close (or equal) to zero or one, overlap weighting (OW) can help mitigate the bias and variance issues associated with IPTW. Although theoretical and simulation results have supported the use of OW with continuous and binary outcomes, its performance with survival outcomes remains to be further investigated, especially when the target estimand is defined based on the restricted mean survival time (RMST). We combine propensity score weighting and inverse probability of censoring weighting to estimate the restricted mean counterfactual survival times, and provide computationally-efficient variance estimators when the propensity scores are estimated by logistic regression and the censoring process is estimated by Cox regression. We conduct simulations to compare the performance of weighting methods in terms of bias, variance, and 95% interval coverage, under various degrees of overlap. Under moderate and weak overlap, we demonstrate the advantage of OW over IPTW, trimming and truncation, with respect to bias, variance, and coverage when estimating RMST.
Board of Pharmacy Specialties 2022 recertification data: Characteristics and perceptions of pharmacists successfully recertified
Authors: LaNou Elizabeth , Meng Yu , Patel Parth , Saiar Amin , Bakken Brianne K 
Published: October 2024

Abstract

Purpose
The purpose of this retrospective study was to utilize existing data to (1) compare the characteristics of Board of Pharmacy Specialties (BPS) credentials successfully recertified vs those that were not successfully recertified in 2022 and (2) compare survey responses about maintaining board certification by continuing pharmacy education (CPE) vs examination among those who successfully recertified.

Summary
The characteristics of BPS credentials eligible for recertification in 2022 (n = 4,812) and survey responses from board-certified pharmacists who successfully recertified in 2022 (n = 3,629) were retrieved from the MyBPS database. Across all specialties, 75.4% of credentials were successfully recertified in 2022. Most credentials were recertified by CPE (92.1%). Successfully recertified credentials were predominately held by pharmacists practicing within the US (96.7%), those between the ages of 31 and 40 years (51.9%), and those completing the first 7-year certification cycle (73.9%). A significant difference was found between recertified credentials and those that were not recertified based on specialty, recertification pathway, credential holder practice location, and credential holder age. Over 89% of respondents reported that a primary benefit of maintaining board certification is to “expand knowledge and skills in pharmacy.”

Conclusion
Several factors influence the decision and/or ability of board-certified pharmacists to recertify and maintain their credentials. Successfully recertified board-certified pharmacists report expanded competency, credibility, personal gratification, and increased confidence among the primary benefits of maintaining board certification. Board-certified pharmacists who successfully recertify also report a preference for a recertification process that is temporally and financially efficient.
Long-term management of moderate-to-severe atopic dermatitis with lebrikizumab and concomitant topical corticosteroids: a 68-week randomized double-blind placebo-controlled phase III trial in Japan (ADhere-J)
Authors: Katoh Norito , Tanaka Akio , Takahashi Hidetoshi , Shimizu Ryosuke , Kataoka Yoko , Torisu-Itakura Hitoe , Morisaki Yoji , Yamamoto Chie , Igawa Ken 
Published: October 2024

Abstract

Background
Moderate-to-severe atopic dermatitis (AD) affects the quality of life of patients. More treatment options are urgently needed to manage this chronic disease. Lebrikizumab is a monoclonal antibody that binds to interleukin-13, a key mediator in AD pathogenesis. In Japanese patients, lebrikizumab has been evaluated through week 16 in the randomized placebo-controlled phase III ADhere-J study.

Objectives
To evaluate the long-term efficacy and safety of lebrikizumab in combination with topical corticosteroids (TCS) in the ADhere-J study.

Methods
Patients aged ≥12 years weighing ≥ 40 kg with moderate-to-severe AD and receiving either subcutaneous lebrikizumab 250 mg ­every 2 weeks (Q2W)/every 4 weeks (Q4W) or placebo during the 16-week induction period were evaluated during the long-term maintenance period from week 16 to week 68. Responders achieved the co-primary endpoints at week 16: an Investigator’s Global Assessment score of 0 or 1 [IGA (0,1)] with ≥ 2-point improvement from baseline and/or ≥ 75% improvement from baseline in Eczema Area and Severity Index (EASI 75). In this analysis, week 16 responders received lebrikizumab 250 mg Q2W or Q4W combined with TCS during the maintenance period (maintenance primary population; MPP); week 16 per-protocol nonresponders received lebrikizumab Q2W with TCS (maintenance escape population; MEP). Major endpoints included IGA (0,1) with ≥ 2-point improvement from baseline and EASI 75 through week 68. Other outcomes included quality of life, itch and serum thymus and activation-regulated chemokine. The trial was registered with ClinicalTrials.gov (NCT04760314).

Results
At week 68, 66–81% of 103 patients in the MPP and 32–38% of 168 patients in the MEP achieved IGA (0,1) with ≥ 2-point improvement from baseline. EASI 75 was maintained by 83–89% of patients in the MPP, while 71–80% of patients in the MEP achieved this outcome by week 68. Across treatment arms, patients in the MPP tended to maintain improvements recorded at week 16, while patients in the MEP steadily improved across the maintenance period. No new safety signals were reported, and most treatment-emergent adverse events were mild or moderate in severity in both populations. Safety outcomes were consistent with previous reports for lebrikizumab treatment in global studies.

Conclusions
These results support the use of lebrikizumab in combination with TCS for the treatment of moderate-to-severe AD in the Japanese population in the long term.
α2δ-2 regulates synaptic GluK1 kainate receptors in Purkinje cells and motor coordination
Authors: Zhou Meng-Hua , Zhou Jing-Jing , Chen Shao-Rui , Chen Hong , Jin Daozhong , Huang Yuying , Shao Jian-Ying , Pan Hui-Lin 
Published: October 2024

Abstract
Gabapentin and pregabalin are inhibitory ligands of both α2δ-1 and α2δ-2 proteins (also known as subunits of voltage-activated Ca2+ channels) and are commonly prescribed for the treatment of neuropathic pain and epilepsy. However, these drugs can cause gait disorders and ataxia through unknown mechanisms. α2δ-2 and GluK1, a glutamate-gated kainate receptor subtype, are coexpressed in cerebellar Purkinje cells. In this study, we used a heterologous expression system and Purkinje cells to investigate the potential role of α2δ-2 in regulating GluK1-containing kainate receptor activity.
Whole-cell patch-clamp recordings showed that α2δ-2 coexpression augmented GluK1, but not GluK2, currents in HEK293 cells, and pregabalin abolished this augmentation. Pregabalin lost its inhibitory effect on GluK1 currents in HEK293 cells expressing both GluK1 and the α2δ-2(R282A) mutant. Blocking GluK1-containing receptors with UBP310 substantially reduced the amplitude of excitatory post-synaptic currents at parallel fibre–Purkinje cell synapses in mice. Also, pregabalin markedly attenuated the amplitude of excitatory post-synaptic currents and currents elicited by ATPA, a selective GluK1 receptor agonist, in Purkinje cells in Cacna2d1 knockout mice. Co-immunoprecipitation assays indicated that α2δ-2, but not α2δ-1, formed a protein complex with GluK1 in cerebellar tissues and HEK293 cells through its C-terminus. Furthermore, α2δ-2 coexpression potentiated surface expression of GluK1 proteins in HEK293 cells, whereas pregabalin reduced GluK1 proteins in cerebellar synaptosomes.
Disrupting α2δ-2–GluK1 interactions using α2δ-2 C-terminus peptide abrogated the potentiating effect of α2δ-2 on GluK1 currents and attenuated the amplitude of GluK1-mediated excitatory post-synaptic currents in Purkinje cells. However, neither pregabalin nor α2δ-2 C-terminus peptide had significant effect on P/Q-type currents in HEK293 cells. Additionally, CRISPR/Cas9-induced conditional knockdown of Cacna2d2 or Grik1 in Purkinje cells, in addition to microinjection of α2δ-2 C-terminus peptide or UBP310 into the cerebellum, substantially impaired beam-walking and rotarod performance in mice.
Our study reveals that α2δ-2 directly interacts with GluK1 independently of its conventional role as a voltage-activated Ca2+ channel subunit. α2δ-2 regulates motor coordination by promoting synaptic expression and activity in GluK1-containing kainate receptors in Purkinje cells.
Adult-onset female focal segmental glomerulosclerosis with nephrotic syndrome caused by a TBC1D8B variant: a case report
Authors: Hu Xiaoying , Cheng Wenrong , Xu Xiaoyi , Sun Lijun , Wang Guoqin , Cheng Hong 
Published: October 2024

ABSTRACT
We report the case of a 49-year-old Chinese woman with nephrotic syndrome, characterized by normal kidney function but poor response to hormonal and immunosuppressive therapy, indicative of steroid-resistant nephrotic syndrome. Through renal biopsy, the patient was diagnosed as havingfocal segmental glomerulosclerosis (perihilar type), and subsequent whole-exome sequencing identified a pathogenic frameshift variant concerning the TBC domain of the TBC1D8B gene. This patient represents the first late-onset Chinese female who was found to carry a novel, pathogenic variant in the gene TBC1D8B.
Real-World Experience of the Association of HLADQA1*05 Allele With Loss of Response to Anti-TNF Inhibitors
Authors: Chokshi Aastha , Raker Christina A , Fine Sean 
Published: October 2024

Abstract

Background
Antitumor necrosis factor (anti-TNF) biologics have revolutionized the treatment of inflammatory bowel disease (IBD). Previously, studies have shown an association between the HLADQA1*05 allele and the development of antibodies and were predictive of loss of response. We sought to investigate the rate of the HLADQA1*05 allele in patients with IBD at a New England center and its association with antibody development and discontinuation of anti-TNF therapy.

Methods
A single center retrospective cohort study with patients on anti-TNF inhibitor therapy being followed at our IBD clinic who had testing performed for the HLADQA1*05 allele were identified and separated into 2 different groups: HLADQA1*05 positive (HLA carriers) or HLADQA1*05 negative (HLA noncarriers). Persistence of remaining on anti-TNF therapy, measurement of drug/antibody levels, and need for dose escalation were collected and stratified amongst the 2 groups.

Results
The prevalence of the HLADQA1*05 allele among all IBD patients followed was 53%. We identified 67 IBD patients being treated with anti-TNF medications, 46 (69%) patients with Crohn’s disease and 21 (31%) with ulcerative colitis. Most of the HLA carriers (85%) and HLA noncarriers (92%) remained on anti-TNF therapy at the end of the study period. Thirty-six (84%) patients had therapeutic drug monitoring performed during maintenance therapy. Three patients in the HLA carrier group had meaningful antidrug antibody levels necessitating cessation of therapy compared to one patient in the HLA noncarrier group (P = .61). Only 3 (13%) of HLA carriers and 4 (21%) of HLA noncarriers were on combination therapy with an immunomodulator. 65% of HLA carriers required dose escalation compared to 50% of HLA noncarriers (P = .70).

Conclusions
The prevalence of the HLADQA1*05 allele was 53% in our New England IBD patient population, similar to what has previously been reported in European studies. The majority of patients remained on anti-TNF therapy at the end of the study period despite carrier status. While there was a trend toward increased need for dose escalation among HLA carriers, this was not statistically significant. Future studies are needed to determine if the presence of the HLADQA1*05 allele leads to antibody development against anti-TNF inhibitors and treatment failure in patients with IBD.
Oral sarcoidosis preceding sudden cardiac arrest: a case report
Authors: Swain William , Castrichini Matteo , Siontis Konstantinos , Hasan Fadi , Arment Courtney 
Published: October 2024

Abstract

Background
Sarcoidosis is a disease characterized by non-caseating granulomas and may affect any organ system. Cardiac involvement may lead to conduction abnormalities, heart failure, or malignant ventricular arrhythmias. As sarcoidosis may present with heterogeneous manifestations, a detailed past medical history may provide clues that help guide further workup. We present a rare case of a patient with undiagnosed oral sarcoidosis who subsequently experienced cardiac arrest from cardiac involvement.

Case summary
A 43-year-old male with a history of palpitations and periodontitis consistent with oral sarcoidosis presents after experiencing sudden cardiac arrest. He was subsequently diagnosed with cardiac and pulmonary sarcoidosis. With contemporary management (both immunosuppression and antiarrhythmics), he has not experienced any recurrent arrhythmias.

Discussion
In the setting of cardiac arrest and non-ischaemic cardiomyopathy, a careful clinical history and targeted cardiac testing may help clinicians determine when to consider cardiac sarcoidosis as a diagnosis. While oral sarcoidosis is a very rare condition, this case highlights how infrequent manifestations of sarcoidosis may be encountered in the clinical setting.
Prediction of new-onset atrial fibrillation in patients with hypertrophic cardiomyopathy using plasma proteomics profiling
Authors: Lumish Heidi S , Harano Nina , Liang Lusha W , Hasegawa Kohei , Maurer Mathew S , Tower-Rader Albree , Fifer Michael A , Reilly Muredach P , Shimada Yuichi J 
Published: October 2024

Abstract

Aims
Atrial fibrillation (AF) is the most common sustained arrhythmia among patients with hypertrophic cardiomyopathy (HCM), increasing symptom burden and stroke risk. We aimed to construct a plasma proteomics-based model to predict new-onset AF in patients with HCM and determine dysregulated signalling pathways.

Methods and results
In this prospective, multi-centre cohort study, we conducted plasma proteomics profiling of 4986 proteins at enrolment. We developed a proteomics-based machine learning model to predict new-onset AF using samples from one institution (training set) and tested its predictive ability using independent samples from another institution (test set). We performed a survival analysis to compare the risk of new-onset AF among high- and low-risk groups in the test set. We performed pathway analysis of proteins significantly (univariable P &lt; 0.05) associated with new-onset AF using a false discovery rate (FDR) threshold of 0.001. The study included 284 patients with HCM (training set: 193, test set: 91). Thirty-seven (13%) patients developed AF during median follow-up of 3.2 years [25–75 percentile: 1.8–5.2]. Using the proteomics-based prediction model developed in the training set, the area under the receiver operating characteristic curve was 0.89 (95% confidence interval 0.78–0.99) in the test set. In the test set, patients categorized as high risk had a higher rate of developing new-onset AF (log-rank P = 0.002). The Ras-MAPK pathway was dysregulated in patients who developed incident AF during follow-up (FDR &lt; 1.0 × 10−6).

Conclusion
This is the first study to demonstrate the ability of plasma proteomics to predict new-onset AF in HCM and identify dysregulated signalling pathways.
Knowledge, attitudes, and practice of primary care professionals regarding community activities: a descriptive study
Authors: Mosteiro-Miguéns Diego G , Zapata-Cachafeiro Maruxa , Novío Silvia , Vieito-Pérez Natalia , Alfonso-González Tania , Rodríguez-Fernández Almudena 
Published: October 2024

Abstract

Background
Promoting health via a community approach is one of the most effective strategies for reducing the current incidence of chronic diseases. Primary care (PC), through the implementation of community activities (CA), has the potential to achieve this goal. Yet the implementation of CA at health centers is not standardized and is often thanks only to the voluntariness of health professionals.

Objective
To ascertain the knowledge, attitudes, and practices of PC professionals regarding the implementation of CA.

Methods
We carried out a cross-sectional study by circulating a self-administered online questionnaire on CA, across the period December 2022 through June 2023 in Galicia (Spain). All health professionals working in the Galician Health Service PC setting were invited to participate.

Results
A total of 521 health professionals participated in the study. They included all types of PC health professionals (physicians, general and specialist nurses -midwives, pediatrics, family and community, mental health- and social workers), including residents in training. Only 14.8% and 12.5% of professionals correctly identified CAs and social prescription (SPr) interventions, respectively. Furthermore, 93.9% recognized that the development of CA in health centers was deficient. Despite this, 76.5% showed a good attitude toward participation in CA.

Conclusions
PC professionals find it difficult to identify CA and SPr interventions. Therefore, it is necessary to improve the training of these professionals in the implementation of CA with a view to enhancing population health, reducing the incidence of chronic diseases, and helping lessen the healthcare burden of the health system.
PePalA/B/C are required for virulence and patulin biosynthesis by regulating the PePacC-processing proteolytic activity in Penicillium expansum
Authors: He Xinghui , Chen Yong , Tian Shiping , Li Boqiang 
Published: October 2024

Abstract

Background
The Pal/Rim signaling pathway is crucial for fungal responses to ambient pH conditions. It comprises the transcription factor PacC/Rim101 and six upstream peptidoglycan-associated lipoprotein (Pal) proteins. While the role of PacC has been extensively studied, there is limited information on the functions of the upstream Pal proteins.

Results
In the genome of Penicillium expansum, genes encoding the endosomal membrane complex (PalA/B/C) were identified. Among these, only the expression of PePalB, not PePalA or PePalC, is pH-dependent. Subcellular localization and functional analyses showed that PePalA/B/C are localized to the cytosol and peripheral punctate structures. Deletion of PePalA/B/C resulted in reduced growth and conidiation of P. expansum across various pH conditions. The virulence of the ΔPePalA/B/C mutant was significantly reduced in pear and apple fruits. Additionally, the mutants exhibited a loss of patulin production under both acidic and alkaline conditions and the downregulation of genes in the patulin biosynthetic cluster. pH shift experiments further demonstrated that PePalA/B/C are essential for both the PePacC expression and the pH-dependent proteolytic activation of PePacC.

Conclusions
These findings highlight the significant roles of PePalA/B/C in regulating growth, conidiation, virulence, and patulin production in P. expansum, thereby enhancing our understanding of the regulatory mechanisms underlying the Pal/Rim signaling pathway.