bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disease extent according to baseline [18F]fluorodeoxyglucose PET/CT and molecular subtype: prediction of axillary treatment response after neoadjuvant systemic therapy for breast cancer
Authors: van Amstel Florien J G , de Mooij Cornelis M , Simons Janine M , Mitea Cristina , van Diest Paul J , Nelemans Patty J , van der Pol Carmen C , Luiten Ernest J T , Koppert Linetta B , Smidt Marjolein L , van Nijnatten Thiemo J A ,   the REFINE Study Group, de Beer L , Boerma E G , Boskamp M , Brouwers-Kuyper E M J , Contant C M E , du Mée A W F , Heijmans H J , Ho-Han S , Hulsebosch F , Jager A , Janssen J A J , Kam B L R , Kelder W , Klem T M A L , Koopmans K P , Lobbes M B I , Menke-Pluijmers M B E , de Monye C , Sars P , Smit L H M , van Haaren E , van Klaveren D , Veltman J , Verhoef C , Vles W J 
Published: September 2024

Abstract

Background
Axillary disease extent according to baseline [18F]fluorodeoxyglucose PET/CT combined with pathological axillary treatment response has been proposed to guide de-escalation of axillary treatment for clinically node-positive breast cancer patients treated with neoadjuvant systemic therapy. The aim of this study was to assess whether axillary disease extent according to baseline [18F]fluorodeoxyglucose PET/CT and breast cancer molecular subtype are predictors of axillary pCR.

Methods
This study included clinically node-positive patients treated with neoadjuvant systemic therapy in the prospective Radioactive Iodine Seed placement in the Axilla with Sentinel lymph node biopsy (‘RISAS’) trial (NCT02800317) with baseline [18F]fluorodeoxyglucose PET/CT imaging available. The predictive value of axillary disease extent according to baseline [18F]fluorodeoxyglucose PET/CT and breast cancer molecular subtype to estimate axillary pCR was evaluated using logistic regression analysis. Discriminative ability is expressed using ORs with 95% confidence intervals.

Results
Overall, 185 patients were included, with an axillary pCR rate of 29.7%. The axillary pCR rate for patients with limited versus advanced baseline axillary disease according to [18F]fluorodeoxyglucose PET/CT was 31.9% versus 26.1% respectively. Axillary disease extent was not a significant predictor of axillary pCR (OR 0.75 (95% c.i. 0.38 to 1.46) (P = 0.404)). There were significant differences in axillary pCR rates between breast cancer molecular subtypes. The lowest probability (7%) was found for hormone receptor+/human epidermal growth factor receptor 2− tumours. Using this category as a reference group, significantly increased ORs of 14.82 for hormone receptor+/human epidermal growth factor receptor 2+ tumours, 40 for hormone receptor−/human epidermal growth factor receptor 2+ tumours, and 6.91 for triple-negative tumours were found (P &lt; 0.001).

Conclusion
Molecular subtype is a significant predictor of axillary pCR after neoadjuvant systemic therapy, whereas axillary disease extent according to baseline [18F]fluorodeoxyglucose PET/CT is not.
Quantitative evaluation of noncovalent interactions with negative fragmentation approach including basis set superposition error correction
Authors: Takano Yu , Kondo Hiroko X , Nakamura Haruki 
Published: September 2024

Abstract
We propose a negative fragmentation approach (NFA), including counterpoise (CP) correction to basis set superposition error (BSSE) for quantitatively evaluating intra- and intermolecular noncovalent interactions. Noncovalent interactions are widely found in chemistry and biology and are regarded as essential interactions. However, there are few general methods for evaluating these individual intra- and intermolecular interaction energies because of two issues: (i) difficulty in the evaluation of intramolecular interactions due to the interacting sites connected with covalent bonds and (ii) BSSE affecting the quantitative accuracy of interaction analysis. In our scheme, we overcome the issue (i) using the NFA scheme, which can evaluate intra- and intermolecular interactions as a fragment–fragment interaction of interacting sites, and address the issue (ii) using the CP method. Here, NFA including the CP correction was also applied to various molecular systems, providing comparable results for intermolecular interactions to supermolecule calculations with the CP correction and succeeding in the evaluation of intramolecular interactions and its BSSEs. It is notable that our NFA scheme does not require any particular program or a modification of the program codes. These indicate that many researchers can apply our NFA scheme to various molecular systems.
Expert Consensus Statement on an Updated Definition of Unintended Weight Loss Among Persons With Human Immunodeficiency Virus in the Modern Treatment Era
Authors: Bedimo Roger , Hardy David , Lee Daniel , Palella Frank , Wohl David 
Published: September 2024

Abstract
The era of modern antiretroviral therapy (ART) has markedly improved health and survival among persons with human immunodeficiency virus (HIV) (PWH). In the pre-ART era, wasting was associated with HIV disease progression to acquired immunodeficiency syndrome and death. Effective ART has reduced the prevalence and incidence of this pre-ART form of HIV-associated wasting. However, a subgroup of ART-treated virally suppressed PWH continue to lose weight, often accompanied by aging-related comorbidities and/or functional deficits. For this subgroup of patients, the older definition of HIV-associated wasting (HIVAW) cannot and should not be applied. An expert panel comprising the authors of this white paper convened to review the existing definition of HIVAW and to create an updated definition that they termed HIV-associated weight loss, based on clinically defined parameters among contemporary PWH receiving ART. Here, clinical features and laboratory biomarkers associated with HIV-associated weight loss are reviewed and approaches to screening and treatment are considered. Available management approaches, including the use of current US Food and Drug Administration–approved medications for HIVAW and other available therapies are discussed. The expert panel also identified knowledge gaps and provided recommendations for clinicians, payers, and researchers.
Double-stranded DNA enhances platelet activation, thrombosis, and myocardial injury via cyclic GMP-AMP synthase
Authors: Zhang Wei , Zhang Yan , Han Liping , Bo Tao , Qi Zhiyong , Zhong Haoxuan , Xu Huajie , Hu Liang , Chen She , Zhang Si 
Published: September 2024

Abstract

Aims
Elevated dsDNA levels in ST-elevated myocardial infarction (STEMI) patients are associated with increased infarct size and worse clinical outcomes. However, the direct effect of dsDNA on platelet activation remains unclear. This study aims to investigate the direct influence of dsDNA on platelet activation, thrombosis, and the underlying mechanisms.

Methods and results
Analysis of clinical samples revealed elevated plasma dsDNA levels in STEMI patients, which positively correlated with platelet aggregation and markers of neutrophil extracellular traps such as MPO-DNA and CitH3. Platelet assays demonstrated the activation of the cGAS–STING pathway in platelets from STEMI patients. DsDNA directly potentiated platelet activation and thrombus formation. Mechanistic studies using G150 (cGAS inhibitor), H151 (STING inhibitor), and MCC950 (NLRP3 inhibitor), as well as cGAS−/−, STING−/−, and NLRP3−/− mice, showed that dsDNA activated cGAS, a previously unreported DNA sensor in platelets, and induced activation of the STING/NLRP3/caspase-1/IL-1β axis. This cascade enhanced platelet activation and thrombus formation. Platelet cGAS depletion or Palbociclib, a cGAS–STING inhibitor, approved by the FDA for advanced breast cancer, ameliorated myocardial ischaemia-reperfusion injury in ApoE−/− mice fed with a high-fat diet for 12 weeks.

Conclusions
These results suggested that dsDNA is a novel driver of platelet activation and thrombus formation in STEMI patients.
The clinical utility of multidisciplinary team meetings for patients with complex benign upper gastrointestinal conditions
Authors: Allaway Matthew G R , Luo Yuchen , Lim Hou Kiat , Bhatia Kiron , Mori Krinal , Craven Alex , Keong Ben , Tog Chek Heng , Sweeney Thomas , Wong Darren , Goodwin Michelle , Leung Christopher , Aly Ahmad , Hall Katheryn , Liu David S 
Published: September 2024

Summary
Patients with benign upper gastrointestinal (UGI) conditions such as achalasia, gastroparesis and refractory gastroesophageal reflux disease often suffer from debilitating symptoms. These conditions can be complex and challenging to diagnose and treat, making them well suited for discussion within a multidisciplinary meeting (MDM). There is, however, a paucity of data describing the value of a benign UGI MDM. The aim of this study was to assess the impact of our unit’s benign UGI MDM service and its outcomes. This was a retrospective analysis of prospectively collected data for all consecutive patients reviewed in the monthly benign UGI MDM between July 2021 and February 2024. The primary outcome was the incidence that MDM review changed clinical treatment. Secondary outcomes included change in diagnosis, additional investigations and referrals to subspecialists.
A total of 104 patients met inclusion criteria. A total of 73 (70.2%) patients had a change in their overall management following MDM review; 25 (24.0%), 31 (29.8%) and 48 (46.2%) patients had changes in pharmacological, endoscopic and surgical interventions respectively. Most changes in pharmacological and endoscopic intervention involved treatment escalation, whereas most changes in surgical intervention involved treatment de-escalation. A total of 84 (80.8%) patients had a documented diagnosis post-MDM with 44 (42.3%) having a change in their pre-MDM diagnosis. 50 (48.1%) patients had additional investigation/s requested and 49 (47.1%) had additional referral pathway/s recommended.
Over two thirds of patients had at least one aspect of their management plan changed following MDM review. These changes occurred across pharmacological, endoscopic, and surgical interventions.
Phenome-wide association study of population-differentiating genetic variants around gene ACSL1
Authors: Yang Shuang , Cai Houjian , Ye Kaixiong 
Published: September 2024

Abstract

Background and objectives
Demographic dynamics and natural selection during human evolution shaped the present-day patterns of genetic variations, and geographically varying genetic factors contribute to different disease prevalences across human populations. This study aims to evaluate the presence of positive selection on the gene encoding long-chain fatty acyl-CoA synthetase 1 (ACSL1) and the phenotypic impacts of population-differentiating genetic variants around this gene.

Methodology
Three types of statistical tests for positive selection, based on site frequency spectrum, extended haplotype homozygosity and population differentiation, were applied to the whole-genome sequencing data from the 1000 Genomes Project. A phenome-wide association study of ACSL1 was performed with published genome-wide association studies (GWAS) and transcriptome-wide association studies, including phenome-wide studies in biobanks.

Results
Genetic variants associated with ACSL1 expression in various tissues exhibit geographically varying allele frequencies. Three types of statistical tests consistently supported the presence of positive selection on the coding and regulatory regions of ACSL1 in African, European, South Asian and East Asian populations. A phenome-wide association study of ACSL1 revealed associations with type 2 diabetes, blood glucose, age at menopause, mean platelet volume and mean reticulocyte volume. The top allele associated with lower diabetes risk has the highest frequency in European populations, whereas the top allele associated with later menopause has the highest frequency in African populations.

Conclusions and implications
Positive selection on ACSL1 resulted in geographically varying genetic variants, which may contribute to differential phenotypes across human populations, including type 2 diabetes and age at menopause.
Relationship between activity and sleep, as measured through a wearable accelerometer, and appropriate cardioverter defibrillator interventions: a prospective SafeHeart substudy
Authors: Frodi Diana M , Kolk Maarten Z H , Diederichsen Søren Z , Langford Joss , Knops Reinoud E , Tan Hanno L , Andersen Tariq O , Jacobsen Peter Karl , Risum Niels , Tjong Fleur V Y , Svendsen Jesper Hastrup 
Published: September 2024

Abstract

Aims
Physical activity has shown association with ventricular arrhythmia, however, the role of specific behavioral patterns over a 24 h cycle remains unknown. Therefore, we aimed to explore associations between physical behavior and appropriate implantable cardioverter defibrillator (ICD) therapy.

Methods and results
We included patients with an ICD at two European sites, who wore wrist-based accelerometers capturing 24 h movement and sleep behaviours for 28 days. Behavioural measures included activity volume, duration and intensity, sleep duration, and efficiency. Participants were followed for 12 months for the outcome of appropriate ICD therapy. Cox proportional hazard models with restricted cubic splines were used for the analysis. Lastly, the predictive capacity was tested. A total of 253 ICD patients were included (mean age 63.5 (±10.2), 48 (19.0%) female). During follow-up, 40 participants (15.8%) received appropriate ICD therapy; 32 anti-tachycardia pacing (ATP) only (12.6%), 5 shock only (2.0%), and 3 combined ATP and shock (1.2%). In the adjusted model, high inactive duration (HR 1.40 (95% 1.10–1.78)), peak walking cadence (HR 1.07 (95% 1.03–1.12)), and total sleep duration (HR 1.50 (1.02–2.22)) were associated with the outcome. The dose–response relationship was U-shaped for inactive duration with a cut-off at 16 h, and linear for peak cadence and sleep. The prediction model reached an area under the receiver operating characteristic curve of 0.70 ± 0.03, with highest accuracy in the first months.

Conclusion
Wearable-derived 24 h movement and sleep behaviours collected over 28 days were associated with later appropriate ICD therapy risk. Testing of the predictive value of digital biomarkers for enhanced risk stratification of ventricular arrhythmia warrants larger prospective studies.

Clinical Trial Registration
National Trial Registration (NL9218, http://onderzoekmetmensen.nl/).
Modelling of 2-D seismic wave propagation in heterogeneous porous media: a frequency-domain finite-element method formulated by variational principles
Authors: Wang Dongdong , Gao Yongxin , Zhou Guanqun , Jiang Yaochang 
Published: September 2024

SUMMARY
We propose a frequency-domain finite-element (FDFE) method to model the 2-D P–SV waves propagating in porous media. This specific finite-element method (FEM) is based on the framework of variational principles, which differs from previously widely used FEMs that rely on the weak formulations of the governing equations. By applying the calculus of variations, we establish the equivalence between solving the stress–strain relations, equations of motion and boundary conditions that govern the propagation of P–SV waves, and determining the extremum or stationarity of a properly defined functional. The structured rectangular element is utilized to partition the entire computational region. We validate the FDFE method by conducting a comparison with an analytically-based method for models of a horizontal planar contact of two poroelastic half-spaces, and a poroelastic half-space with a free surface. The excellent agreements between the analytically-based solutions and the FDFE solutions indicate the effectiveness of the FDFE method in modelling the poroelastic waves. Modelling results manifest that both propagative and diffusive natures of the Biot slow P wave can be effectively modelled. The proposed FDFE method simulates wavefields in the frequency domain, allowing for easy incorporation of frequency-dependent parameters and enabling parallel computational capabilities at each frequency point (sample). We further employ the developed FDFE method to model two simplified poroelastic reservoirs, one with gas-saturated sandstone and the other with oil-saturated sandstone. The results suggest that changing the fluid phase of the sandstone reservoir from gas to oil can substantially impact the recorded solid and relative fluid–solid displacements. The modelling suggests that the proposed FDFE algorithm is a useful tool for studying the propagation of poroelastic waves.
Effect of Viral Antigen Mismatch on Antiviral T-Cell Response and Immunotherapeutic Efficacy Against Adult T-Cell Leukemia/Lymphoma
Authors: Sugata Kenji , Takatori Mitsuyoshi , Reda Omnia , Tan Benjy Jek Yang , Tokunaga Masahito , Sato Tomoo , Ueda Mitsuharu , Yamano Yoshihisa , Utsunomiya Atae , Satou Yorifumi 
Published: September 2024

Abstract
Human T-cell leukemia virus type 1 (HTLV-1) transforms primary CD4 T cells in vitro within a short time; however, majority of infected individuals maintain an asymptomatic condition, suggesting that there is an equilibrium between the infected cells and the host immunity. In this study, we identified a variation in a major viral antigen epitope, HTLV-1 Tax301–309, in HLA-A24–positive individuals. Mismatch in A24/Tax301–309 multimers impaired detection of anti-Tax cytotoxic T lymphocytes (CTLs). Notably, more than half of the T-cell receptors (TCRs) of the anti-Tax CTLs did not recognize mismatched Tax301–309 peptides. These findings highlighted the importance of matching the viral antigen epitope type in T-cell–based immunotherapy against adult T-cell leukemia/lymphoma by using viral antigen Tax.
Unpredicted Protective Function of Fc-Mediated Inhibitory Antibodies for HIV and SARS-CoV-2 Vaccines
Authors: Lin Li-Yun , Gantner Pierre , Li Shuang , Su Bin , Moog Christiane 
Published: September 2024

Abstract
Developing effective vaccines is necessary in combating new virus pandemics. For human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the induction of neutralizing antibodies (NAb) is important for vaccine protection; however, the exact mechanisms underlying protection require further study. Recent data emphasize that even Abs that do not exhibit neutralizing activity may contribute to immune defense by Ab Fc-mediated inhibition. Abs exhibiting this function may counter virus mutations, which are acquired to escape from NAbs, and therefore broaden the protective Ab response induced by vaccination. The steps leading to inhibition are complex. How can these functions be measured in vitro? What inhibitory assay is physiologically relevant at mimicking effective in vivo protection? This review provides a comprehensive update on the current knowledge gaps on the Ab Fc-mediated functions involved in HIV and SARS-CoV-2 protection. Understanding the inhibitory effects of these Abs is vital for designing the next generation of protective HIV and SARS-CoV-2 vaccines.
Optimizing warfarin and dual oral anticoagulation practices in an academic clinic during a merger amid the COVID-19 pandemic in a marginalized population
Authors: Bahuva Ronak , Jordan Jacquelyn , Pokharel Yadunath , Reynolds Jessica L , Bakhai Smita 
Published: September 2024

Abstract
Background: The closure of a pharmacy-led anticoagulation clinic, which provided point-of-care (POC) international normalized ratio (INR) testing and face-to-face visits, coupled with the transition to an academic physician-led clinic without POC INR testing and reliance on telephone communication, created significant challenges for warfarin management during the Coronavirus disease 2019 pandemic. The aim of this quality control project was to increase the percentage of patients on warfarin within the optimal time in therapeutic range (TTR) from 52.30% to 65.00%, sustain baseline quarterly cumulative percentage TTR to 59.00%, and transition 20% of eligible patients from warfarin to dual oral anticoagulation (DOAC) within 12 months.
Methods: A multidisciplinary team employed a Fishbone diagram, stakeholder analysis, process flow map, and a driver diagram. Significant barriers included knowledge gaps, fear of blood draws, lack of POC INR testing, and noninteroperable electronic health records (EHRs). Primary outcome measures included quarterly cumulative percentage TTR, 2-monthly percentage TTR, and the percentage of eligible patients switched to DOAC. Process measures included INR completion rates. Key interventions involved educating patients and the care team, transitioning patients to DOAC, improving EHRs, and optimizing processes. Data analysis utilized run charts.
Results: Monthly INR completion rates rose from 63% to 87% within 12 months and reached 92% during the 6 months post-project period. Among 143 patients, 40.55% (58) were eligible for a DOAC switch, with 51.72% (30/58) successfully transitioning during the project and the 6-month post-project period. Two-monthly TTR rates improved from the baseline of 52.30% to 62.00% during the study period and remained sustainable at 62.80% in the post-project phase. Quarterly cumulative TTR rates remained stable at 59.20% during the study period in 2021. The quarterly cumulative TTR rates continued to increase at 60.50% and 64.40% in 2022 and 2023, respectively, during the post-project period. No bleeding episodes occurred during the 15-month post-project period.
Conclusion: Multi-faceted strategies significantly improved warfarin safety during the project and maintained these improvements for 24 months. Transitioning from warfarin to DOACs was crucial for optimizing anticoagulation management with limited resources. The lead physician and team used various tools to address barriers to effective warfarin management, ensure appropriate DOAC prescribing, and enhance practices for DOAC prescriptions. This project effectively addressed barriers, improved population health, and provided a model for anticoagulation management in primary care settings.
She Said No: Toward a Survivor-Centered History of Vajrayāna Buddhist Sexuality
Authors: Jacoby Sarah H 
Published: September 2024

Abstract
As a contribution toward survivor-centered approaches to the study of religion and sex abuse that centers historical Tibetan Buddhist women, this article focuses on key passages from the autobiography of Sera Khandro Dewai Dorjé (1892–1940), through which a nuanced vision of Vajrayāna technologies of sexuality emerges. Drawing on insights from feminist historiography, this article listens to Sera Khandro’s portrayal of Vajrayāna sexual ethics, including her critiques of the hypocrisy of lust-driven men masquerading as celibate monks and sexual yoga virtuosos, as well as her articulations of sexual yoga as potentially liberatory. Through these passages we will hear the many ways Sera Khandro refused sex, even when it was proffered in the name of salvation, with the aim of making it harder to weaponize the weight of Buddhist tradition to justify sexual predation.