bluuebunny/crossref_metadata_2025_split huggingface dataset:
UNRAVELING GENDER DISPARITIES AND PROGNOSTIC INSIGHTS IN MODERATE AORTIC STENOSIS: A RETROSPECTIVE STUDY
Authors: Guareschi A , Donisi L , Pasero G , Mallardi G , Faggiano A , Faggiano P , Bursi F , Santangelo G , Carugo S 
Published: May 2024

Abstract
Aortic stenosis (AS) is the most prevalent valvular heart disease in developed countries, associated with reduced survival if severe AS remains untreated. Recent reports note unfavorable outcomes in moderate AS (mAS) patients, challenging optimal intervention timing. Variations in pathophysiology linked to sex differences, involving sex hormones, activation of the renin–angiotensin–aldosterone system, and dysregulation in collagen synthesis, have been observed. Yet, limited data exists on sex–specific differences in mAS outcomes. This single–center, retrospective study included 150 patients (median age 79±13 years, female sex 48%) diagnosed with mAS who underwent comprehensive echocardiography in IRCCS Fondazione Ca’ Granda Ospedale Maggiore Policlinico of Milan from July 2022 to October 2023. Clinical data, encompassing demographics details and therapy, were obtained via record reviews and phone interviews. Death verification relied on the ‘Sistema Informativo Socio–Sanitario Regione Lombardia’ database. Echocardiographic records were digitally stored and post–processed by four independent investigators using Medimatic ComPACS workstation. Men were significantly younger than women (75±10 vs 79±9.7 years, p= 0.016). They exhibited lower left ventricular (LV) ejection fraction, larger LV end–systolic volume and stroke volume compared to women (54±7 vs 59±10%; p=0.028. 55±36 vs 31±13 ml; p&lt;0.001. 83±18 vs 75±18 ml; p=0.030). Men had significantly smaller aortic valve (AV) area index to body surface area (BSA) (0.6±0.09 vs 0.7±0.1 cmq/mq; p&lt;0.001) and lower doppler velocity index (0.32±0.07 vs 0.38±0.11; p&lt;0.001) than women. Coronary artery disease and smoking were more frequent in men (53.3 vs 46.7%; p=0,002. 52.6 vs 47.4%; p&lt;0.001). In survival analysis, 15% of women and 30.8% of men experienced events, with male gender independently associated with the composite outcome (all–cause mortality and AV replacement) over a mean follow–up time of 200 ± 133 days, showing a median survival of 244±16 vs 255±15 days for females (p–value=0.025). In multivariable analysis including relevant clinical variables (hemoglobin and AV index to BSA), male sex remained independently associated with the composite outcome (hazard ratio 2,01; CI 1.0–4.17; p=0.05). Women diagnosed with mAS exhibited a lower incidence of AV replacement and all–cause mortality. These findings may suggest the existence of different clinical and echocardiographic phenotypes among patients with AS.
RELATION BETWEEN CALCIUM METABOLISM AND DEVELOPMENT OF AORTIC VALVE STENOSIS
Authors: Ferrari V , Mazzanti C , De Biase L 
Published: May 2024

Abstract
The role of calcium metabolism in the development of degenerative Aortic Valve Stenosis (AVS) is not completely understood. Valvular cell modifications and passive calcification can be both involved in the diseases. Vitamin D (Vit D) and Parathyroid Hormone (PTH) are important factor in calcium regulation and data on their modification in AVS are scanty. Their potential role in AVS prevention is not yet identified. Osteocalcin can be considered a marker of calcification and its potential usefulness in identification of patient at risk for AVS was not studied. In order to correlate calcium metabolism to AVS development we have studied PTH, Vit D and Osteocalcin in a population of patients with AVS. We recruited 100 patients admitted in our Cardiac Surgery Unit for AVS confirmed by electrocardiogram, echocardiogram and hemodynamic evaluation. Subjects with rheumatic or congenital valvulopathy and infectious endocarditis were excluded from the study. Calcium, phosphorus, calcium–phosphorus ratio (Ca/P ratio), PTH, Vit D, renal function and osteocalcin were measured in each patient. In our population, 93.5% of patients had low levels of Vit D (&lt;30 ng / ml), 42.4% had elevated levels of PTH (&gt;38.4 pg / ml) and 28% had low levels of osteocalcin (&lt;14 ng / ml). 87% of the population had normal calcium levels (8.4–10.2 mg / dl) and 93.3% had normal levels of phosphoremia (2.7–4.5 mg / dl). Defining as normal a Ca/P ratio between 1.5 and 2.5, 60.7% of our population had high levels of Ca/P. In conclusion, our findings suggest that patients suffering from AVS have abnormal levels of factors involved in the regulation of calcium metabolism. Some factors can be target for preventive therapies.
The platform fix: analyzing mechanisms and contradictions of how digital platforms tackle pending urban-economic challenges
Authors: Repenning Alica , Hardaker Sina 
Published: May 2024

Abstract
Digital platforms, such as Google, Amazon, or Instagram, provide a promising spatial fix to urban-economic problems by leveraging technology and data while connecting stakeholders and overcoming spatial barriers to make urban life, consumption, sales, and production more efficient. This article contributes to the debate on digital platforms in economic geography by advancing the emerging lens of the platform fix, adopting a critical standpoint concerning the solutionist viewpoint that presents platforms as a fix for various challenges. The article develops its perspective against the background of 57 semi-structured interviews, 200 conducted standardized questionnaires, and long-term on/offline observations. We aim to provide a platform fix perspective revealing how digital platforms redefine spatial interactions, addressing economic challenges through spatial fixes while becoming established as indispensable infrastructures; however, platform fixes often fail to address underlying issues, leading to platform dependencies and the instrumentalization of actors. Therefore, we suggest a cautious application of urban platforms as solutions and critically evaluate the formation of public–private platform partnerships.
Proximal survival analysis to handle dependent right censoring
Authors: Ying Andrew 
Published: May 2024

Abstract
Many epidemiological and clinical studies aim to analyse a time-to-event endpoint. A common complication is right censoring. In some cases, right censoring occurs when subjects are still surviving after the study terminates or move out of the study area. In such cases, right censoring is typically treated as independent or noninformative. This assumption can be further relaxed to conditional independent censoring by leveraging possibly time-varying covariate information, if available, and assuming censoring and failure time are independent within covariate strata. In yet other instances, events may be censored by other competing events like death and are associated with censoring possibly through prognoses. Realistically, measured covariates can rarely capture all such associations with absolute certainty. In cases of dependent censoring, covariate measurements are often, at best, proxies of underlying prognoses. In this article, we establish a nonparametric identification framework by formally admitting that conditional independent censoring may fail in practice and accounting for covariate measurements as imperfect proxies of underlying association. The framework suggests adaptive estimators, and we provide generic assumptions under which they are consistent, asymptotically normal, and doubly robust. We examine the finite-sample performance of our proposed estimators via a Monte Carlo simulation and apply them to the SEER-Medicare dataset.
Clinical utility of anti-Ro52 antibody confirmation in anti-MDA5 antibody-positive dermatomyositis: A case report
Authors: Kodera Hitoshi , Hirano Reina , Akiyama Masahiro , Matsumoto Yoshifuji 
Published: May 2024

ABSTRACT
This case report highlights dermatomyositis (DM) characterised by the concurrent presence of anti-melanoma differentiation-associated protein 5 (anti-MDA5) and anti-Ro52 antibodies. A 64-year-old woman initially presented with erythema on the palms, which later spread to the dorsum of the hands, followed by involvement of the face, forehead, and upper eyelids. The patient reported joint pain, fatigue, and dyspnea. Physical examination revealed characteristic cutaneous manifestations, including heliotrope rash and Gottron’s sign, accompanied by skin ulceration and muscle weakness. Blood tests showed elevated levels of creatine phosphokinase and C-reactive protein. A high-resolution computed tomography (HRCT) scan revealed interstitial lung disease (ILD) with an organising pneumonia (OP) pattern. Magnetic resonance imaging (MRI) confirmed the presence of myositis. Autoantibody analysis revealed concurrent positivity for both anti-MDA5 and anti-Ro52 antibodies. At the time of diagnosis, she had no respiratory impairment, but had an elevated C-reactive protein and high levels of anti-MDA5 antibody. She was started on triple combination therapy with glucocorticoids, cyclophosphamide, and tacrolimus. She had worsening oxygenation and elevated ferritin during the first weeks of treatment, but then her symptoms improved. Early detection of a co-positive anti-Ro52 antibody led to early initiation of triple combination therapy and a good prognosis.
Calcium pyrophosphate crystal arthritis associated with immune checkpoint inhibitor successfully treated with intra-articular glucocorticoid: A case report
Authors: Abe Kazuya , Iwamoto Taro , Ikeda Kei , Sugiyama Takahiro , Furuta Shunsuke , Saito Go , Wakabayashi Hanae , Nakajima Hiroshi 
Published: May 2024

ABSTRACT
Immune checkpoint inhibitors (ICIs) sometimes induce immune-related adverse events (irAEs), and arthritis is one of the irAE symptoms. Recently, crystal-induced arthritis, such as calcium pyrophosphate (CPP) crystal deposition disease and gout, has been reported to occur after ICI administration. However, the distinction between ICI-associated crystal arthritis and ICI-induced non-crystal arthritis is difficult because their symptoms are similar. Besides, optimal treatment for ICI-associated crystal arthritis has not been established. Here, we report a patient who developed CPP crystal arthritis twice after pembrolizumab (ICI) administration and was successfully treated with intra-articular glucocorticoid injection. He suffered arthritis and acute interstitial nephritis simultaneously after ICI administration. Musculoskeletal ultrasound of his affected joint suggests that his arthritis was crystal-induced arthritis, and arthrocentesis detected CPP crystal in synovial fluid. Thus, we diagnosed his arthritis as ICI-associated crystal arthritis. Therefore, our case encourages the use of musculoskeletal ultrasound in patients with arthritis after treatment with ICI because it may distinguish between ICI-associated crystal arthritis and ICI-induced non-crystal arthritis. Besides, ICI-associated crystal arthritis could be treatable by intra-articular glucocorticoid injection.
A NAC transcription factor represses a module associated with xyloglucan content and regulates aluminum tolerance
Authors: Li Su , Yang Ji Bo , Li Jia Qi , Huang Jing , Shen Ren Fang , Zeng Da Li , Zhu Xiao Fang 
Published: May 2024

Abstract
The transcriptional regulation of aluminum (Al) tolerance in plants is largely unknown, although Al toxicity restricts agricultural yields in acidic soils. Here, we identified a NAM, ATAF1/2, and cup-shaped cotyledon 2 (NAC) transcription factor that participates in Al tolerance in Arabidopsis (Arabidopsis thaliana). Al substantially induced the transcript and protein levels of ANAC070, and loss-of-function mutants showed remarkably increased Al sensitivity, implying a beneficial role of ANAC070 in plant tolerance to Al toxicity. Further investigation revealed that more Al accumulated in the roots of anac070 mutants, especially in root cell walls, accompanied by a higher hemicellulose and xyloglucan level, implying a possible interaction between ANAC070 and genes that encode proteins responsible for the modification of xyloglucan, including xyloglucan endo-transglycosylase/hydrolase (XTH) or ANAC017. Yeast 1-hybrid analysis revealed a potential interaction between ANAC070 and ANAC017, but not for other XTHs. Furthermore, dual-luciferase reporter assay, RT-qPCR, and GUS analysis revealed that ANAC070 could directly repress the transcript levels of ANAC017, and knockout of ANAC017 in the anac070 mutant partially restored its Al sensitivity phenotype, indicating that ANAC070 contributes to Al tolerance mechanisms other than suppression of ANAC017 expression. Further analysis revealed that the core transcription factor SENSITIVE TO PROTON RHIZOTOXICITY 1 (STOP1) and its target genes, which control Al tolerance in Arabidopsis, may also be involved in ANAC070-regulated Al tolerance. In summary, we identified a transcription factor, ANAC070, that represses the ANAC017-XTH31 module to regulate Al tolerance in Arabidopsis.
D-ꞵ-hydroxybutyrate stabilizes hippocampal CA3-CA1 circuit during acute insulin resistance
Authors: Kula Bartosz , Antal Botond , Weistuch Corey , Gackière Florian , Barre Alexander , Velado Victor , Hubbard Jeffrey M , Kukley Maria , Mujica-Parodi Lilianne R , Smith Nathan A 
Published: May 2024

Abstract
The brain primarily relies on glycolysis for mitochondrial respiration but switches to alternative fuels such as ketone bodies (KBs) when less glucose is available. Neuronal KB uptake, which does not rely on glucose transporter 4 (GLUT4) or insulin, has shown promising clinical applicability in alleviating the neurological and cognitive effects of disorders with hypometabolic components. However, the specific mechanisms by which such interventions affect neuronal functions are poorly understood. In this study, we pharmacologically blocked GLUT4 to investigate the effects of exogenous KB D-ꞵ-hydroxybutyrate (D-ꞵHb) on mouse brain metabolism during acute insulin resistance (AIR). We found that both AIR and D-ꞵHb had distinct impacts across neuronal compartments: AIR decreased synaptic activity and long-term potentiation (LTP) and impaired axonal conduction, synchronization, and action potential properties, while D-ꞵHb rescued neuronal functions associated with axonal conduction, synchronization, and LTP.
Exploring overlooked growth-promoting mechanisms by plant-associated bacteria
Authors: Danchin Antoine 
Published: May 2024

Abstract
Agriculture-oriented microbiome studies try to develop microbiota beneficial to their plant hosts. This positive goal extends to the soil quality driving plant growth and disease resistance. In research aimed at identifying the causes of this beneficial action, a common interpretation is that microbes will synthesize metabolites useful to their hosts. This view assumes that important microbial metabolites are exported for use by their hosts. Yet, this seems unlikely for essential metabolites, without a counterpart imported from the plants, as the corresponding syntheses would often involve the consumption of resources without explicit benefit to the microbes. Illustrating this function with the example of Bacilli of the Subtilis clade, we emphasize here that the most direct access to the contents of microbial cells is through cell lysis, a phenomenon often linked to the process of sporulation. This process also releases macromolecules that are digested in the environment, releasing key metabolites such as queuine, an important base analog present in the anticodon of some transfer RNAs. This overlooked importance of cell lysis could also be a major cause of the ubiquitous presence of bacteriophages in microbiota.
Renal disease in pediatric rheumatology
Authors: Cody Ellen , Brunner Hermine I. 
Published: May 2024

Purpose of review
This review will provide updates in the outcomes in the common rheumatologic diseases with kidney involvement. Covered are also advances in therapeutics for the use of pediatric rheumatologic diseases with kidney involvement, as well as the potential kidney complications from other rheumatologic diseases and their medications.

Recent findings
Two of the more common rheumatologic diseases with kidney involvement, lupus and vasculitis, continue to show inadequate response to initial therapy of renal disease and practice continues to be driven by results of adult studies.

Summary
There is a continued need for pediatric specific studies in rheumatologic diseases with kidney involvement as outcomes continue to be inadequate. Despite recently approved treatments for adults with rheumatic diseases and kidney involvement, therapeutic options in pediatrics remain limited, contributing to the overall morbidity and mortality.
Multiple brain abscesses in a neonate: a rare case report along with review of literature
Authors: Mehta Aanand , Yadav Manish , Gupta Bishal K. , Thapa Bikash , Rai Junu , Thapa Surya B. , Yadav Sudip K. , Yadav Digraj , Sharma Mohan R. 
Published: May 2024

Introduction and importance:
Brain abscess (BA) is a pyogenic infection of the brain parenchyma caused by various organisms. Multiple BAs are uncommon in neonates, and Candida albicans as a causative agent is very rare. If left untreated, BAs are invariably fatal. Early diagnosis, prompt surgical intervention, simultaneous eradication of the primary source, and high-dose intravenous antibiotics decrease the incidence of morbidity and mortality.

Case presentation:
A 20-day-old newborn, delivered normally at term with a full APGAR score, presented with a 5-day history of fever, decreased activity, jaundice, and seizures. Imaging identified multiple cerebral cysts, diagnosed as multiple cerebral abscesses. Treatment involved intraoperative USG-guided burr-hole drainage, followed by a 6-week antifungal therapy course. C. albicans was found to be the causative organism following microscopic examination and culture of the pus.

Clinical discussion:
This literature highlights the rarity of fungal involvement in multiple cerebral abscesses in neonates. Managing such cases is very challenging, as the presentation may mimic bacterial infections. The importance of considering fungi as a causative agent in treatment decisions is crucial.

Conclusion:
Multiple BAs of fungal origin are extremely rare. Early detection and management of cases can reduce mortality among neonates.
Rheumatoid Arthritis–Related Lung Disease and Its Association With Mortality
Authors: Sahin Didem , Colaklar Anil , Baysal Serdar , Torgutalp Murat , Baygul Asaf , Sezer Serdar , Aydemir Guloksuz Emine G. , Yuksel Mehmet L. , Yayla Mucteba E. , Uslu Emine , Uzun Caglar , Ozdemir Kumbasar Ozlem , Turgay Tahsin M. , Kinikli Gulay , Ates Askin 
Published: May 2024

Purpose
The aim of this study was to determine the association of rheumatoid arthritis–related lung disease (RA-LD) and its subtypes with all-cause mortality.

Materials and Methods
For the present analyses, patients with RA who underwent computed tomography of the chest (chest-CT) were evaluated. RA-LD was defined in 4 subtypes as follows: interstitial lung disease (RA-ILD), airway disease (RA-AD), rheumatoid pulmonary nodules (RA-PN), and RA-related pleural disease (RA-PD). The date of RA-LD diagnosis was considered the date of the first chest-CT detecting the pathology. To assess the factors associated with mortality, multivariable logistic regression analyses were performed with variables selected based on their causal associations with the outcome.

Results
Of 576 RA patients, 253 (43.9%) had RA-LD (38.7% male; mean age at RA-LD diagnosis, 59.9 ± 9.8 years). The most common subtype was RA-AD, which was detected in 119 (47.0%) patients followed by 107 (42.3%) with RA-ILD, 70 (27.7%) with RA-PN, and 31 (12.3%) with RA-PD. Sixty-one (24.1%) patients had 2+ subtypes. After median follow-up of 10.2 years, 97 (16.8%) died. The existence of at least 1 subtype and 2+ subtypes increased the all-cause mortality, as indicated by odds ratios of 1.60 (95% confidence interval [CI], 1.03–2.48) and 2.39 (95% CI, 1.26–4.54), respectively. Among RA-LD patients, RA-ILD and RA-PD were associated with increased mortality (odds ratios were 2.20 [95% CI, 1.18–4.08] and 1.62 [95% CI, 0.70–3.75], respectively).

Conclusions
In this study, RA-AD was the most common subtype, and the presence of RA-LD increased mortality. This effect was particularly pronounced in patients with RA-ILD and RA-PD or those presenting with 2+ subtypes.
Histopathologic Predictors for Locoregional Recurrence in Patients With Oral Squamous Cell Carcinoma – A Single-Center Retrospective Study
Authors: Jolly Satnam Singh , Rattan Vidya , Parasuraman Lingesh , Mitra Suvradeep , Singh Apoorva 
Published: May 2024

Background:
Oral squamous cell carcinoma (OSCC) is known for its aggressive behavior and the high potential for locoregional recurrence (LRR), contributing to poor prognostic outcomes. The aim of this study was to investigate the role of histologic parameters in predicting LRR in patients with OSCC.

Materials and Methods:
A retrospective analysis was performed on 58 OSCC patients treated between January 2018 and December 2022. Data were collected from medical records, focusing on demographics, clinicopathologic features, and treatment details. Different histopathologic factors such as depth of invasion, tumor stage (T), pathologic node stage (N), histologic grade of differentiation, perineural invasion, lymphovascular invasion, extranodal extension (ENE), and margin of resection were correlated with LRR.

Results:
Out of 58 patients, 20 (34.4%) reported LRR within the first year of follow-up. In the recurrence group, 14 patients succumbed to death within 24 months. Among all the histopathologic parameters, our study found a statistically significant correlation between higher pathologic node stage, presence of ENE, and closest margin of resection (≤5 mm) with LRR.

Conclusion:
Higher pathologic node stage, presence of ENE, and closest margin of resection (≤5 mm) were the histopathologic factors associated with LRR, and can serve as deciding prognostic factors. Treatment intensification in early-stage disease with higher pathologic nodal stage, presence of ENE, and closest margin of resection (≤5 mm) may improve survival outcomes.
Association of Collagen Changes in Distal Anastomotic Margin and Anastomotic Stenosis after Neoadjuvant Chemoradiotherapy for Rectal Cancer
Authors: Feng Mingyuan , Wang Huaiming , Zheng Jixiang , Chen Zhenbang , Kang Bingzi , Zhao Yandong , Yao Jiaxin , Wang Hui , Zhuo Shuangmu , Yan Jun 
Published: May 2024

BACKGROUND:
Neoadjuvant chemoradiotherapy (nCRT) for rectal cancer can lead to structural changes in collagen in the tumor microenvironment and increase the risk of postoperative anastomotic stenosis (AS). However, the quantitative relationship between AS and collagen has not been defined. This study is to quantitatively analyze the collagen features in rectal cancer and explore the relationship between the changes of collagen and postoperative anastomotic stenosis after nCRT.

STUDY DESIGN:
This is a retrospective study. A total of 371 patients with rectal cancer were included. Collagen features in the resection margin of rectal cancer anastomosis was extracted by multiphoton imaging. The least absolute shrinkage operator logistic regression was performed to select features related to AS and the collagen score (CS) was constructed. Area under the receiver operating curve (AUROC) and decision curve analysis were performed to evaluate the discrimination and clinical benefit of the nomogram.

RESULTS:
The probability of AS was 23% in the training cohort and 15.9% in the validation cohort. In the training cohort, the distance between tumor and resection margin, anastomotic leakage and CS were independent risk factors for postoperative AS in univariate and multivariate analyses. A nomogram was constructed based on these results. The prediction nomogram showed good discrimination (AUROC 0.864; 95% CI 0.776 to 0.952) and was validated in the validation cohort (AUROC 0.918; 95% CI 0.851 to 0.985).

CONCLUSIONS:
CS is an independent risk factor for AS in rectal cancer after nCRT. The predictive model based on CS can predict the occurrence of postoperative AS.