bluuebunny/crossref_metadata_2025_split huggingface dataset:
JC virus spread is potentiated by glial replication and demyelination-linked glial proliferation
Authors: Li Cui , Huynh Nguyen P T , Schanz Steven J , Windrem Martha S , Goldman Steven A 
Published: August 2024

Abstract
Progressive multifocal leukoencephalopathy is a demyelinating infection of the immunosuppressed brain, mediated by the gliotropic polyomavirus JCV. JCV replicates in human glial progenitor cells and astrocytes, which undergo viral T-antigen-triggered mitosis, enabling viral replication. We asked whether JCV spread might therefore be accelerated by glial proliferation.
Using both in vitro analysis and a human glial chimeric mouse model of JCV infection, we found that dividing human astrocytes supported JCV propagation to a substantially greater degree than did mitotically quiescent cells. Accordingly, bulk and single-cell RNA-sequence analysis revealed that JCV-infected glia differentially manifested cell cycle-linked disruption of both DNA damage response and transcriptional regulatory pathways. In vivo, JCV infection of humanized glial chimeras was greatly accentuated by cuprizone-induced demyelination and its associated mobilization of glial progenitor cells. Importantly, in vivo infection triggered the death of both uninfected and infected glia, reflecting significant bystander death.
Together, these data suggest that JCV propagation in progressive multifocal leukoencephalopathy might be accelerated by glial cell division. As such, the accentuated glial proliferation attending disease-associated demyelination might provide an especially favourable environment for JCV propagation, thus potentiating oligodendrocytic bystander death and further accelerating demyelination in susceptible hosts.
Histological features of immune cell infiltrate in lesional skin correlate with therapeutic response to dupilumab
Authors: Gori Niccolò , Chiricozzi Andrea , Sfregola Stefania , Ippoliti Elena , Di Stefani Alessandro , Malvaso Dalma , Di Nardo Lucia , Federico Francesco , Zannoni Gian Franco , Peris Ketty 
Published: August 2024

Abstract
Over the past decade, dupilumab, a monoclonal human antibody that inhibits interleukin (IL)-4 and IL-13 signalling, has revolutionized the therapeutic management of moderate-to-severe atopic dermatitis (AD), facilitating long-term control of its signs and symptoms. The aim of this study was to identify histological predictors of the efficacy of dupilumab after 16 weeks of treatment in a cohort of 40 adults with moderate-to-severe AD who had undergone a skin biopsy for diagnostic purposes before treatment initiation. We found that Eczema Area and Severity Index (EASI) 75 and EASI 90 responses at week 16 were significantly associated with perivascular localization [odds ratio (OR) 17.6; P = 0.04] and lichenoid distribution (OR 31.8; P = 0.03) of the immune infiltrate. Moreover, for each unit increase in the number (cells mm–2) of CD4+ cells, the likelihood of achieving an EASI 75 response decreased by 1% (OR 0.99; P = 0.04). In conclusion, our study found promising pretreatment immunohistochemical markers that could predict how well patients with AD respond to dupilumab.
Prevalence and clinical significance of anti-SSA antibody in the Chinese health screening population
Authors: Jia Yimeng , Luan Shuqi , Huang Sicheng , Zhang Wen , Li Mengtao , Xu Tengda , Fei Yunyun 
Published: August 2024

Abstract
Anti-Sjögren's syndrome type A (anti-SSA) antibodies are non-organ-specific autoantibodies highly prevalent in various autoimmune diseases. This study primarily investigated the prevalence of anti-SSA antibodies in the health screening population. Additionally, we explored the clinical features of the anti-SSA antibody-positive population and evaluated the development of connective tissue diseases (CTD) over the years in individuals with anti-SSA antibodies for whom follow-up was available. A total of, 64 045 individuals without a history of CTD from 2013 to 2022 who visited Peking Union Medical College Hospital for health screening were screened for autoimmune antibodies: 1.7% (1091/64 045) of the Chinese health screening population were positive for anti-SSA antibodies, with a prevalence of 0.9% (290/33 829) in men and 2.7% (801/30 216) in women. Compared with matched autoantibody-negative controls, anti-SSA antibody-positive individuals had higher levels of serological abnormalities, including erythrocyte sedimentation rate (ESR) [10 (6–15) mm/h vs. 7 (4–12) mm/h, P &lt; 0.0001], rheumatoid factor (RF) [7.15 (4.30–16.90) IU/ml vs. 5.00 (3.20–7.90) IU/ml, P &lt; 0.0001], and immunoglobulin G [13.09 (11.20–15.45) g/L vs. 11.34 (9.85–13.18) g/L, P &lt; 0.0001], and lower levels of white blood cells (WBC; 5.49 ± 1.50 × 109/L vs. 5.82 ± 1.49 × 109/L, P &lt; 0.0001). Additionally, they had a higher proportion of coexisting thyroid autoantibodies, including anti-thyroid peroxidase antibodies (TPO-Ab) (17.1% vs. 11.3%, P &lt; 0.0001) and anti-thyroglobulin antibodies (Tg-Ab) (17.8% vs. 11.0%, P &lt; 0.0001). Among the 381 subjects who were anti-SSA positive and followed up for a median of 4.6 years, 146 (38.3%) individuals developed CTD, including 68 (17.8%) cases of primary Sjögren’s syndrome (pSS), 10 (2.6%) cases of rheumatoid arthritis (RA), 5 (1.3%) cases of systemic lupus erythematosus (SLE), 4 (1.0%) cases of secondary Sjögren’s syndrome (sSS), and 59 (15.5%) cases of undifferentiated connective tissue disease (UCTD). In all, 235 (61.7%) individuals did not develop CTD over a median time of 5.9 (2.9–8.1) years after the earliest autoantibody detection. Elevated ESR (&gt;20 mm/h), RF positivity (&gt;20 IU/ml), and female gender were identified as independent risk factors for CTD among the anti-SSA antibody-positive individuals. Anti-SSA antibodies were found in 17 among approximately 1000 individuals without a history of autoimmune diseases. Anti-SSA antibody-positive individuals are advised to periodically monitor thyroid function. Elevated ESR (&gt;20 mm/h), female gender, and RF positivity may delineate a high-risk cohort for CTDs.
Medial to lateral frontal functional connectivity mapping reveals the organization of cingulate cortex
Authors: Ducret Marion , Giacometti Camille , Dirheimer Manon , Dureux Audrey , Autran-Clavagnier Delphine , Hadj-Bouziane Fadila , Verstraete Charles , Lamberton Franck , Wilson Charles R E , Amiez Céline , Procyk Emmanuel 
Published: August 2024

Abstract
The functional organization of the frontal lobe is a source of debate, focusing on broad functional subdivisions, large-scale networks, or local refined specificities. Multiple neurocognitive models have tried to explain how functional interactions between cingulate and lateral frontal regions contribute to decision making and cognitive control, but their neuroanatomical bases remain unclear. We provide a detailed description of the functional connectivity between cingulate and lateral frontal regions using resting-state functional MRI in rhesus macaques. The analysis focuses on the functional connectivity of the rostral part of the cingulate sulcus with the lateral frontal cortex. Data-driven and seed-based analysis revealed three clusters within the cingulate sulcus organized along the rostro-caudal axis: the anterior, mid, and posterior clusters display increased functional connectivity with, respectively, the anterior lateral prefrontal regions, face–eye lateral frontal motor cortical areas, and hand lateral frontal motor cortex. The location of these clusters can be predicted in individual subjects based on morphological landmarks. These results suggest that the anterior cluster corresponds to the anterior cingulate cortex, whereas the posterior clusters correspond to the face–eye and hand cingulate motor areas within the anterior midcingulate cortex. These data provide a comprehensive framework to identify cingulate subregions based on functional connectivity and local organization.
Anterior cingulate cortex lesions impair multiple facets of task engagement not mediated by dorsomedial striatum neuron firing
Authors: Vázquez Daniela , Peña-Flores Norma , Maulhardt Sean R , Solway Alec , Charpentier Caroline J , Roesch Matthew R 
Published: August 2024

Abstract
The anterior cingulate cortex (ACC) has been implicated across multiple highly specialized cognitive functions—including task engagement, motivation, error detection, attention allocation, value processing, and action selection. Here, we ask if ACC lesions disrupt task performance and firing in dorsomedial striatum (DMS) during the performance of a reward-guided decision-making task that engages many of these cognitive functions. We found that ACC lesions impacted several facets of task performance—including decreasing the initiation and completion of trials, slowing reaction times, and resulting in suboptimal and inaccurate action selection. Reductions in movement times towards the end of behavioral sessions further suggested attenuations in motivation, which paralleled reductions in directional action selection signals in the DMS that were observed later in recording sessions. Surprisingly, however, beyond altered action signals late in sessions—neural correlates in the DMS were largely unaffected, even though behavior was disrupted at multiple levels. We conclude that ACC lesions result in overall deficits in task engagement that impact multiple facets of task performance during our reward-guided decision-making task, which—beyond impacting motivated action signals—arise from dysregulated attentional signals in the ACC and are mediated via downstream targets other than DMS.
Laminar pattern of sensory-evoked dynamic high-frequency oscillatory activity in the macaque auditory cortex
Authors: Kajikawa Yoshinao , Mackey Chase A , O’Connell Monica Noelle 
Published: August 2024

Abstract
High-frequency (&gt;60 Hz) neuroelectric signals likely have functional roles distinct from low-frequency (&lt;30 Hz) signals. While high-gamma activity (&gt;60 Hz) does not simply equate to neuronal spiking, they are highly correlated, having similar information encoding. High-gamma activity is typically considered broadband and poorly phase-locked to sensory stimuli and thus is typically analyzed after transformations into absolute amplitude or spectral power. However, those analyses discard signal polarity, compromising the interpretation of neuroelectric events that are essentially dipolar. In the spectrotemporal profiles of field potentials in auditory cortex, we show high-frequency spectral peaks not phase-locked to sound onset, which follow the broadband peak of phase-locked onset responses. Isolating the signal components comprising the high-frequency peaks reveals narrow-band high-frequency oscillatory events, whose instantaneous frequency changes rapidly from &gt;150 to 60 Hz, which may underlie broadband high-frequency spectral peaks in previous reports. The laminar amplitude distributions of the isolated activity had two peak positions, while the laminar phase patterns showed a counterphase relationship between those peaks, indicating the formation of dipoles. Our findings suggest that nonphase-locked HGA arises in part from oscillatory or recurring activity of supragranular-layer neuronal ensembles in auditory cortex.
PITX2 deficiency leads to atrial mitochondrial dysfunction
Authors: Reyat Jasmeet S , Sommerfeld Laura C , O’Reilly Molly , Roth Cardoso Victor , Thiemann Ellen , Khan Abdullah O , O’Shea Christopher , Harder Sönke , Müller Christian , Barlow Jonathan , Stapley Rachel J , Chua Winnie , Kabir S Nashitha , Grech Olivia , Hummel Oliver , Hübner Norbert , Kääb Stefan , Mont Lluis , Hatem Stéphane N , Winters Joris , Zeemering Stef , Morgan Neil V , Rayes Julie , Gehmlich Katja , Stoll Monika , Brand Theresa , Schweizer Michaela , Piasecki Angelika , Schotten Ulrich , Gkoutos Georgios V , Lorenz Kristina , Cuello Friederike , Kirchhof Paulus , Fabritz Larissa 
Published: August 2024

Abstract

Aims
Reduced left atrial PITX2 is associated with atrial cardiomyopathy and atrial fibrillation (AF). PITX2 is restricted to left atrial cardiomyocytes (aCMs) in the adult heart. The links between PITX2 deficiency, atrial cardiomyopathy, and AF are not fully understood.

Methods and results
To identify mechanisms linking PITX2 deficiency to AF, we generated and characterized PITX2-deficient human aCMs derived from human induced pluripotent stem cells (hiPSC) and their controls. PITX2-deficient hiPSC-derived atrial cardiomyocytes showed shorter and disorganized sarcomeres and increased mononucleation. Electron microscopy found an increased number of smaller mitochondria compared with isogenic controls. Mitochondrial protein expression was altered in PITX2-deficient hiPSC-derived atrial cardiomyocytes. Single-nuclear RNA-sequencing found differences in cellular respiration pathways and differentially expressed mitochondrial and ion channel genes in PITX2-deficient hiPSC-derived atrial cardiomyocytes. PITX2 repression in hiPSC-derived atrial cardiomyocytes replicated dysregulation of cellular respiration. Mitochondrial respiration was shifted to increased glycolysis in PITX2-deficient hiPSC-derived atrial cardiomyocytes. PITX2-deficient human hiPSC-derived atrial cardiomyocytes showed higher spontaneous beating rates. Action potential duration was more variable with an overall prolongation of early repolarization, consistent with metabolic defects. Gene expression analyses confirmed changes in mitochondrial genes in left atria from 42 patients with AF compared with 43 patients with sinus rhythm. Dysregulation of left atrial mitochondrial (COX7C) and metabolic (FOXO1) genes was associated with PITX2 expression in human left atria.

Conclusion
PITX2 deficiency causes atrial mitochondrial dysfunction and a metabolic shift to glycolysis in human aCMs. PITX2-dependent metabolic changes can contribute to the structural and functional defects found in PITX2-deficient atria.
Evaluating the impacts of digital ECG denoising on the interpretive capabilities of healthcare professionals
Authors: McKenna Stacey , McCord Naomi , Diven Jordan , Fitzpatrick Matthew , Easlea Holly , Gibbs Austin , Mitchell Andrew R J 
Published: August 2024

Abstract

Aims
Electrocardiogram (ECG) interpretation is an essential skill across multiple medical disciplines; yet, studies have consistently identified deficiencies in the interpretive performance of healthcare professionals linked to a variety of educational and technological factors. Despite the established correlation between noise interference and erroneous diagnoses, research evaluating the impacts of digital denoising software on clinical ECG interpretation proficiency is lacking.

Methods and results
Forty-eight participants from a variety of medical professions and experience levels were prospectively recruited for this study. Participants’ capabilities in classifying common cardiac rhythms were evaluated using a sequential blinded and semi-blinded interpretation protocol on a challenging set of single-lead ECG signals (42 × 10 s) pre- and post-denoising with robust, cloud-based ECG processing software. Participants’ ECG rhythm interpretation performance was greatest when raw and denoised signals were viewed in a combined format that enabled comparative evaluation. The combined view resulted in a 4.9% increase in mean rhythm classification accuracy (raw: 75.7% ± 14.5% vs. combined: 80.6% ± 12.5%, P = 0.0087), a 6.2% improvement in mean five-point graded confidence score (raw: 4.05 ± 0.58 vs. combined: 4.30 ± 0.48, P &lt; 0.001), and 9.7% reduction in the mean proportion of undiagnosable data (raw: 14.2% ± 8.2% vs. combined: 4.5% ± 2.4%, P &lt; 0.001), relative to raw signals alone. Participants also had a predominantly positive perception of denoising as it related to revealing previously unseen pathologies, improving ECG readability, and reducing time to diagnosis.

Conclusion
Our findings have demonstrated that digital denoising software improves the efficacy of rhythm interpretation on single-lead ECGs, particularly when raw and denoised signals are provided in a combined viewing format, warranting further investigation into the impact of such technology on clinical decision-making and patient outcomes.
The AORTA Gene score for detection and risk stratification of ascending aortic dilation
Authors: Pirruccello James P , Khurshid Shaan , Lin Honghuang , Weng Lu-Chen , Zamirpour Siavash , Kany Shinwan , Raghavan Avanthi , Koyama Satoshi , Vasan Ramachandran S , Benjamin Emelia J , Lindsay Mark E , Ellinor Patrick T 
Published: August 2024

Abstract

Background and Aims
This study assessed whether a model incorporating clinical features and a polygenic score for ascending aortic diameter would improve diameter estimation and prediction of adverse thoracic aortic events over clinical features alone.

Methods
Aortic diameter estimation models were built with a 1.1 million-variant polygenic score (AORTA Gene) and without it. Models were validated internally in 4394 UK Biobank participants and externally in 5469 individuals from Mass General Brigham (MGB) Biobank, 1298 from the Framingham Heart Study (FHS), and 610 from All of Us. Model fit for adverse thoracic aortic events was compared in 401 453 UK Biobank and 164 789 All of Us participants.

Results
AORTA Gene explained more of the variance in thoracic aortic diameter compared to clinical factors alone: 39.5% (95% confidence interval 37.3%–41.8%) vs. 29.3% (27.0%–31.5%) in UK Biobank, 36.5% (34.4%–38.5%) vs. 32.5% (30.4%–34.5%) in MGB, 41.8% (37.7%–45.9%) vs. 33.0% (28.9%–37.2%) in FHS, and 34.9% (28.8%–41.0%) vs. 28.9% (22.9%–35.0%) in All of Us. AORTA Gene had a greater area under the receiver operating characteristic curve for identifying diameter ≥ 4 cm: 0.836 vs. 0.776 (P &lt; .0001) in UK Biobank, 0.808 vs. 0.767 in MGB (P &lt; .0001), 0.856 vs. 0.818 in FHS (P &lt; .0001), and 0.827 vs. 0.791 (P = .0078) in All of Us. AORTA Gene was more informative for adverse thoracic aortic events in UK Biobank (P = .0042) and All of Us (P = .049).

Conclusions
A comprehensive model incorporating polygenic information and clinical risk factors explained 34.9%–41.8% of the variation in ascending aortic diameter, improving the identification of ascending aortic dilation and adverse thoracic aortic events compared to clinical risk factors.
Towards a thorough understanding of mammalian glycosylphosphatidylinositol-anchored protein biosynthesis
Authors: Kinoshita Taroh 
Published: August 2024

Abstract
Glycosylphosphatidylinositols (GPIs) are glycolipids found ubiquitously in eukaryotes. They consist of a glycan and an inositol phospholipid, and act as membrane anchors of many cell-surface proteins by covalently linking to their C-termini. GPIs also exist as unlinked, free glycolipids on the cell surface. In human cells, at least 160 proteins with various functions are GPI-anchored proteins. Because the attachment of GPI is required for the cell-surface expression of GPI-anchored proteins, a thorough knowledge of the molecular basis of mammalian GPI-anchored protein biosynthesis is important for understanding the basic biochemistry and biology of GPI-anchored proteins and their medical significance. In this paper, I review our previous knowledge of the biosynthesis of mammalian GPI-anchored proteins and then examine new findings made since 2020.
Use of an emulated trial to investigate the association between use of nitrogen-based bisphosphonates and risk of epithelial ovarian cancer
Authors: Tuesley Karen M , Spilsbury Katrina , Webb Penelope M , Pearson Sallie-Anne , Donovan Peter , Coory Michael D , Steer Christopher B , Stewart Louise M , Pandeya Nirmala , Protani Melinda M , Dixon-Suen Suzanne , Marquart-Wilson Louise , Jordan Susan J 
Published: August 2024

Abstract

Background
Epithelial ovarian cancer (EOC) is the eighth most common cancer in women, with poor survival outcomes. Observational evidence suggests that nitrogen-based bisphosphonate (NBB) use may be associated with reduced risk of EOC, particularly the endometrioid and serous histotypes; however, confounding by indication is a concern. An alternative approach to investigate the chemo-preventive potential of NBBs is to emulate a target trial by identifying all women who initiate use of NBBs and investigate the risk of EOC for continued users compared with discontinued users.

Methods
Using population-based linked data, we identified all Australian women aged over 50 years who first used NBBs over 2004–12. We used the year after first use to define treatment for each woman as either continued or discontinued use. We emulated randomization using stabilized inverse probability weights to balance the treatment groups using covariates including age, comorbidities and socioeconomic status. We followed women from treatment assignment until EOC diagnosis, death or 31 December 2013. We assessed the risk of EOC (overall and by histotype) using flexible parametric time-to-event models allowing for time-varying effects, and produced time-varying coefficients.

Results
Of the 313 383 women in the study, 472 were diagnosed with EOC during follow-up (261 serous EOC), with an average age at diagnosis of 72 years. Continued use of NBBs was associated with reduced risk of EOC overall (HR = 0.87, 95% CI: 0.69, 1.10), and serous EOC (HR = 0.71, 95% CI: 0.53, 0.96), compared with discontinued treatment, with estimates remaining constant over the 9-year follow-up.

Conclusions
Results from our emulated trial suggest that in women who initiated NBB treatment, those who continued use had 13% and 29% lower hazards of being diagnosed with EOC overall and serous EOC, respectively, compared with women who discontinued use.
The Limits of Enforcement in Global Financial Governance: Blacklisting in FATF as Rational Myth
Authors: Case-Ruchala Devin , Nance Mark 
Published: August 2024

Abstract
How might international institutions matter? To consider this central question of International Relations, we analyze a most-likely case for the importance of materially driven enforcement: the Financial Action Task Force’s (FATF) use of blacklisting in the global regime targeting money laundering and terrorism financing. Scholars and practitioners often argue that fear of financial harm caused by FATF’s lists explains the near-global commitment to FATF’s standards, even if compliance lags. We search for statistical evidence of this impact across four different measures of financial flows and find that listing is not correlated with financial harm. To explain these null results, we examine bank decision-making and find that the lists’ impact is likely diminished by two overlooked factors: the existence of multiple, competing lists and banks’ access to more fine-grained, client-specific information provided by third-party companies. We interpret this contradiction—a commitment to compliance generated in part by a fear of enforcement, despite a lack of evidence for enforcement’s impact—as a “rational myth.” The results challenge a common understanding of a major global governance regime, confirm ideas about the limited ability of states or International Organizations to control governance outcomes, and advance a new research agenda on the impact of bank decision-making on global governance.