bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of Behçet disease with oral roflumilast: an observational study
Authors: Peñuelas Leal Rodrigo , Labrandero Hoyos Carolina , Peñuelas Ruiz Jose Amancio , Bagán Leticia , Zaragoza Ninet Violeta , Sánchez Carazo Jose Luis , Pérez Pastor Gemma , Grau Echevarría Andrés , Esteve Martínez Altea , Finello Malena , Blaya Imbernon Daniel , Dios Guillán Víctor , Aguilar González Lucía , Bagán José , Alegre De Miquel Victor 
Published: July 2024

Abstract

Background
Mucocutaneous Behçet disease often presents a therapeutic challenge. Roflumilast has shown promise in the treatment of other inflammatory dermatological conditions.

Objectives
The objective of this study was to evaluate the characteristics, effectiveness and safety of roflumilast in the treatment of Behçet disease-associated aphthosis in routine clinical practice.

Methods
We performed a single-cohort ambispective observational study. Eleven patients with Behçet disease treated with roflumilast participated. Data collection included demographic, clinical and outcome variables. Statistical analysis compared 12 weeks of treatment with roflumilast with a previous period without treatment and with a period when the previous treatment was used.

Results
During treatment with roflumilast, a reduction in flare-ups and oral ulcers was observed compared with the untreated period and the previous treatment period. A reduction in genital ulcers, pain and ulcer duration was observed between the without treatment period and the roflumilast treatment period. Adverse effects occurred in 54% of patients, most of which were self-limiting or manageable with dose adjustment. No patients withdrew treatment.

Conclusions
Roflumilast appears to be a potential option in the treatment of Behçet disease with favourable effectiveness, safety and tolerability profiles. Although further research is needed, roflumilast offers a promising treatment option for Behçet disease-associated aphthosis, which could improve the patients’ quality of life and address unmet therapeutic needs.
Structural and functional abnormalities and cognitive profiles in older adults with early-onset and late-onset focal epilepsy
Authors: Wan Xinyue , Zeng Yanwei , Wang Jianhong , Tian Mei , Yin Xuyang , Zhang Jun 
Published: July 2024

Abstract
This study aimed to determine the patterns of changes in structure, function, and cognitive ability in early-onset and late-onset older adults with focal epilepsy (OFE). This study first utilized the deformation-based morphometry analysis to identify structural abnormalities, which were used as the seed region to investigate the functional connectivity with the whole brain. Next, a correlation analysis was performed between the altered imaging findings and neuropsychiatry assessments. Finally, the potential role of structural-functional abnormalities in the diagnosis of epilepsy was further explored by using mediation analysis. Compared with healthy controls (n = 28), the area of reduced structural volume was concentrated in the bilateral cerebellum, right thalamus, and right middle cingulate cortex, with frontal, temporal, and occipital lobes also affected in early-onset focal epilepsy (n = 26), while late-onset patients (n = 31) displayed cerebellar, thalamic, and cingulate atrophy. Furthermore, correlation analyses suggest an association between structural abnormalities and cognitive assessments. Dysfunctional connectivity in the cerebellum, cingulate cortex, and frontal gyrus partially mediates the relationship between structural abnormalities and the diagnosis of early-onset focal epilepsy. This study identified structural and functional abnormalities in early-onset and late-onset focal epilepsy and explored characters in cognitive performance. Structural-functional coupling may play a potential role in the diagnosis of epilepsy.
Economic growth and the foreign sector: Peru 1821–2020
Authors: Varona Luis , Gonzales Jorge R , García Benjamín , Gismera Laura 
Published: July 2024

Abstract
Thirlwall Model shows evidence in Latin American countries, as well as for the Peruvian economy, with an economic growth rate of balance of payments equilibrium, which is explained by causal variables that present a long-term cointegration relationship. These variables are exports with little added value, imports that reinforce technological dependence, external income, relative prices or the real exchange rate, the institutions, and the volatility of exports. Investment policies are prescribed in innovative, physical, financial, natural, and social human capital that tend to reduce the restriction of foreign exchange, technological dependence and the international market. Therefore, endogenous, dynamic, sustained, inclusive economic growth is generated, low in carbon as a means for sustainable human development, within the framework of a new growth and development strategy that involves balancing the participation of the market, state and civil society.
Immune-related adverse event-myocarditis with marked ST-segment elevation requiring differentiation from COVID-19-induced myocarditis: a case report
Authors: Fujita Kana , Ohashi Yoshitaka , Nagasawa Yoshinori , Otani Tomoyuki , Hatakeyama Kinta 
Published: July 2024

Abstract

Background
Immunotherapy with immune checkpoint inhibitors (ICIs) enhances the host immune reaction against tumour cells by inhibiting intrinsic down-regulators of the T cell-mediated immune response. Although the advent of ICIs has dramatically changed oncology, ICIs may also trigger an overactivation of T cells against non-cancerous tissues, leading to off-target immune-related adverse events (irAEs).

Case summary
A 64-year-old man with a history of seven courses of atezolizumab, an ICI, for small-cell lung cancer and coronavirus disease 2019 (COVID-19) was admitted to the hospital complaining of acute chest pain. Transthoracic echocardiography showed preserved ejection fraction (EF), but electrocardiography indicated precordial ST-elevations and marked increases in biomarkers for myocardial injury were observed. Emergent cardiac catheterization showed no significant coronary stenosis. On the fifth hospital day, EF decreased to 25% and pericardial effusion occurred. Endomyocardial biopsy was immediately performed, and prednisolone (60 mg/day) was administered. Troponin I level rapidly reduced, ST changed, and EF improved. Histological examinations demonstrated CD8-predominant T lymphocytic infiltration with myocardial cell injury, consistent with irAE-myocarditis.

Discussion
In irAEs, myocarditis is the most common and severe cardiac manifestation with a high mortality. Even at 20 weeks after the initial ICI treatment, irAE-myocarditis occurs and the clinical presentation may mimic ST-elevation myocardial infarction. The histopathological findings suggested the high possibility of irAE-myocarditis rather than COVID-19-induced myocarditis, but COVID-19 has possibly played a role in the development of late-onset irAE-myocarditis. This educational case implies the importance of immediate recognition of irAE even after stable ICI treatment.
Ventricular volume asymmetry as a novel imaging biomarker for disease discrimination and outcome prediction
Authors: McCracken Celeste , Szabo Liliana , Abdulelah Zaid A , Condurache Dorina-Gabriela , Vago Hajnalka , Nichols Thomas E , Petersen Steffen E , Neubauer Stefan , Raisi-Estabragh Zahra 
Published: July 2024

Abstract

Aims
Disruption of the predictable symmetry of the healthy heart may be an indicator of cardiovascular risk. This study defines the population distribution of ventricular asymmetry and its relationships across a range of prevalent and incident cardiorespiratory diseases.

Methods and results
The analysis includes 44 796 UK Biobank participants (average age 64.1 ± 7.7 years; 51.9% women). Cardiovascular magnetic resonance (CMR) metrics were derived using previously validated automated pipelines. Ventricular asymmetry was expressed as the ratio of left and right ventricular (LV and RV) end-diastolic volumes. Clinical outcomes were defined through linked health records. Incident events were those occurring for the first time after imaging, longitudinally tracked over an average follow-up time of 4.75 ± 1.52 years. The normal range for ventricular symmetry was defined in a healthy subset. Participants with values outside the 5th-95th percentiles of the healthy distribution were classed as either LV dominant (LV/RV &gt; 112%) or RV dominant (LV/RV &lt; 80%) asymmetry. Associations of LV and RV dominant asymmetry with vascular risk factors, CMR features, and prevalent and incident cardiovascular diseases (CVDs) were examined using regression models, adjusting for vascular risk factors, prevalent diseases, and conventional CMR measures. Left ventricular dominance was linked to an array of pre-existing vascular risk factors and CVDs, and a two-fold increased risk of incident heart failure, non-ischaemic cardiomyopathies, and left-sided valvular disorders. Right ventricular dominance was associated with an elevated risk of all-cause mortality.

Conclusion
Ventricular asymmetry has clinical utility for cardiovascular risk assessment, providing information that is incremental to traditional risk factors and conventional CMR metrics.
Role of myocardial microRNAs in the long-term ventricular remodelling of patients with aortic stenosis
Authors: Gabriel André F , Costa Marina C , Caldeira Daniel , Plácido Rui , Rigueira Joana , Carrilho-Ferreira Pedro , Gonçalves Susana , Ferreira Ricardo , Nobre Ângelo , Pinto Fausto J , Enguita Francisco J , Almeida Ana G 
Published: July 2024

Abstract

Aims
We hypothesize that miRs are key players in the dynamics of the hypertrophy phenotype in aortic stenosis (AS) patients. In our study, we aimed to identify the transcriptional patterns (protein-coding transcripts and miRs) from myocardial sample biopsies that could be associated with the absence of left ventricular (LV) mass regression after aortic valve replacement (AVR) in patients with severe AS and LV hypertrophy.

Methods and results
We prospectively included 40 patients with severe AS, LV hypertrophy, and preserved ejection fraction undergoing AVR. Myocardial biopsies obtained during surgery were analysed for transcriptomic analysis performed by next-generation sequencing. At a 1-year follow-up, no hypertrophy reversal was observed in about half of the patients in the absence of patient–prosthesis mismatch and prosthesis dysfunction of uncontrolled hypertension. Predictors of mass regression were assessed from clinical, echocardiographic, and biochemical variables as well as from 300 miRs obtained from myocardial specimens, allowing the identification 29 differentially expressed. miR-4709-3p was found as a positive independent predictor of hypertrophy regression together with high-sensitivity troponin T (cTNT-hs) as a negative predictor. Gene transcripts RFX1, SIX5, MAPK8IF3, and PKD1 were predicted as simultaneous targets of five upregulated miRs suggesting its importance in LV hypertrophy.

Conclusion
In our cohort, tissue miR-4709-3p and cTNT-hs were independent predictors of hypertrophy regression. The hypertrophy reversal process will likely depend from a complex network where miRNAs may have an important role, allowing a potential opportunity for therapy.
The Road to Crime: An Unintended Consequence of the Interstate Highway System
Authors: Calamunci Francesca , Lonsky Jakub 
Published: July 2024

Abstract
The necessity to overhaul national infrastructure has become one of the key issues of US domestic policy in recent years. While the benefits of infrastructure spending are often straightforward, its unintended consequences are less well understood. This paper studies the impact of transportation infrastructure on local crime, focusing on the construction of the Interstate Highway System, the largest public works project in US history. Using a staggered difference-in-differences design and a county-by-year panel dataset spanning all US counties between 1960 and 1993, we find that a highway opening in a county led to an 8% rise in total index crime. This effect is driven by property crime (burglary, larceny and motor vehicle theft), although some evidence suggests an increase in violent crime as well. Exploring potential mechanisms, we show that the positive effect of highways on crime is concentrated in counties with low pre-existing stock of police resources where increased connectivity may have raised the returns to crime. Moreover, we find that highway construction induced higher local employment, average firm size and the local population size, thus increasing the returns to criminal activity, and ultimately the risk of victimisation in the newly connected counties.
‘There was a star riding through clouds one night, and I said to the star, “Consume me”’: Post-human extinction in Virginia Woolf’s The Waves
Authors: Case Oliver 
Published: July 2024

Abstract
Human beings are now in a period of the Earth’s history during which their extinction seems ever more probable due to extreme climate change, global pandemics, international conflicts, and lack of long-term intergovernmental or transnational cooperation to tackle these threats to life. Concern for the future of humanity is not, however, a uniquely contemporary phenomenon. Several of Virginia Woolf’s late novels suggest an awareness of the potential for human extinction. Where this concern can be found in The Waves (1931), the text does not express nihilism or panic at the prospect. Instead, the idea of a world without humans is seized as the provocation to continue an experiment which runs throughout Woolf’s writing: to reimagine the relationship between the human and the non-human. By exploring this writerly concern in The Waves, this essay argues that Woolf also redefines human death by reconceptualizing the natural world in ways which undo anthropocentric understandings of the potential extinction of the human species. By re-reading Woolf’s seventh novel through ecocritical practices and alongside ideas from contemporary post-humanist critical theory, the analyses proposed herein suggest that The Waves encourages a reassessment of our position in and response to a human-made environmental crisis which threatens the future of existence, human and non-human, in the twenty-first century.
Furanocoumarin profiles and inhibitory effects on cytochrome P450 activity of whole citrus fruit
Authors: Sun Yujing , Wang Yihua , Zhang Le , Ye Xingqian , Guo Jingtong 
Published: July 2024

Abstract
Furanocoumarins in citrus fruit can cause adverse drug interactions; however, there are few reports on furanocoumarins and drug interactions in common edible citrus cultivars except grapefruit. An ultra-performance liquid chromatography (UPLC)–based method for ten furanocoumarins in citrus fruit was established, and the effects on cytochrome P450 activity were investigated. Furanocoumarins were more abundant (2–43 times) in the peel than in the pulp. The pulp of Xiyou, Hongyou, and Navel orange exhibited P450 inhibition, with 50% maximal inhibitory concentration (IC50) values of 0.63, 0.67, and 1.02 mg/mL, respectively. The peel of all the varieties except Huyou and Satsuma exhibited P450 inhibition. Xiyou, Baiyou, Huangjinyou, Hongyou, Ponkan, and Navel orange had IC50 values of 0.33, 0.76, 0.38, 0.35, 0.43, and 0.37 mg/mL, respectively. These findings indicate that, except for Xiyou, Hongyou, and Navel orange, the consumption of the pulp of popular Chinese varieties of citrus fruit has a low risk of drug interactions, and the use of citrus products including peel may carry a significant risk of adverse drug interactions.
Transposon-sequencing (Tn-seq) of the Candida glabrata reference strain CBS138 reveals epigenetic plasticity, structural variation, and intrinsic mechanisms of resistance to micafungin
Authors: Nickels Timothy J , Gale Andrew N , Harrington Abigail A , Timp Winston , Cunningham Kyle W 
Published: July 2024

Abstract
Candida glabrata (also called Nakaseomyces glabratus) is an opportunistic pathogen that can resist common antifungals and rapidly acquire multidrug resistance. A large amount of genetic variation exists between isolates, which complicates generalizations. Portable transposon-sequencing (Tn-seq) methods can efficiently provide genome-wide information on strain differences and genetic mechanisms. Using the Hermes transposon, the CBS138 reference strain and a commonly studied derivative termed 2001 were subjected to Tn-seq in control conditions and after exposure to varying doses of the clinical antifungal micafungin. The approach revealed large differences between these strains, including a 131-kb tandem duplication and a variety of fitness differences. Additionally, both strains exhibited up to 1,000-fold increased transposon accessibility in subtelomeric regions relative to the BG2 strain, indicative of open subtelomeric chromatin in these isolates and large epigenetic variation within the species. Unexpectedly, the Pdr1 transcription factor conferred resistance to micafungin through targets other than CDR1. Other micafungin resistance pathways were also revealed including mannosyltransferase activity and biosynthesis of the lipid precursor sphingosine, the inhibition of which by SDZ 90–215 and myriocin enhanced the potency of micafungin in vitro. These findings provide insights into the complexity of the C. glabrata species as well as strategies for improving antifungal efficacy.
HLA-DQA1*05 correlates with increased risk of anti-drug antibody development and reduced response to infliximab in Chinese patients with Crohn’s disease
Authors: Wang Wei , Zhang Qi , Zhao Junzhang , Liu Tao , Yao Jiayin , Peng Xiang , Zhi Min , Zhang Min 
Published: July 2024

Abstract

Background
The efficacy of anti-TNF therapy in Crohn’s disease (CD), such as infliximab, is often compromised by the development of anti-drug antibodies (ADAs). The genetic variation HLA-DQA1*05 has been linked to the immunogenicity of biologics, influencing ADA formation. This study investigates the correlation between HLA-DQA1*05 and ADA formation in CD patients treated with infliximab in a Chinese Han population and assesses clinical outcomes.

Methods
In this retrospective cohort study, 345 infliximab-exposed CD patients were genotyped for HLADQ A1*05A&gt;G (rs2097432). We evaluated the risk of ADA development, loss of infliximab response, adverse events, and treatment discontinuation among variant and wild-type allele individuals.

Results
A higher percentage of patients with ADAs formation was observed in HLA-DQA1*05 G variant carriers compared with HLA-DQA1*05 wild-type carriers (58.5% vs 42.9%, P = 0.004). HLA-DQA1*05 carriage significantly increased the risk of ADAs development (adjusted hazard ratio = 1.65, 95% CI 1.18–2.30, P = 0.003) and was associated with a greater likelihood of infliximab response loss (adjusted HR = 2.55, 95% CI 1.78–3.68, P &lt; 0.0001) and treatment discontinuation (adjusted HR = 2.21, 95% CI 1.59–3.06, P &lt; 0.0001). Interestingly, combined therapy with immunomodulators increased the risk of response loss in HLA-DQA1*05 variant carriers.

Conclusions
HLA-DQA1*05 significantly predicts ADAs formation and impacts treatment outcomes in infliximab-treated CD patients. Pre-treatment screening for this genetic factor could therefore be instrumental in personalizing anti-TNF therapy strategies for these patients.
Interventional endoscopy in inflammatory bowel disease: a comprehensive review
Authors: Pal Partha , Reddy D Nageshwar 
Published: July 2024

Abstract
Interventional endoscopy can play a key role in the multidisciplinary management of complex inflammatory bowel disease (IBD) as an adjunct to medical and surgical therapy. The primary role of interventional IBD (IIBD) includes the treatment of Crohn’s disease-related stricture, fistula, and abscess. Endoscopic balloon dilation (EBD), endoscopic stricturotomy, and placement of endoscopic stents are different forms of endoscopic stricture therapy. EBD is the most widely used therapy whereas endoscopic stricturotomy has higher long-term efficacy than EBD. Fully covered and partially covered self-expanding metal stents are useful in long and refractory strictures whereas lumen-apposing metal stents can be used in short, and anastomotic strictures. Endoscopic fistula/abscess therapy includes endoscopic fistulotomy, seton placement, endoscopic ultrasound-guided drainage of rectal/pelvic abscess, and endoscopic injection of filling agents (fistula plug/glue/stem cell). Endoscopic seton placement and fistulotomy are mainly feasible in short, superficial, single tract fistula and in those with prior surgical seton placement. Similarly, endoscopic fistulotomy is usually feasible in short, superficial, single-tract fistula. Endoscopic closure therapies like over-the-scope clips, suturing, and self-expanding metal stent should be avoided for de novo/bowel to hollow organ fistulas. Other indications include management of postoperative complications in IBD such as management of surgical leaks and complications of pouchitis in ulcerative colitis. Additional indications include endoscopic resection of ulcerative colitis-associated neoplasia (by endoscopic mucosal resection, endoscopic submucosal dissection, and endoscopic full-thickness resection), retrieval of retained capsule endoscope, and control of bleeding. IIBD therapies can potentially act as a bridge between medical and surgical therapy for properly selected IBD patients.
Power equipment image enhancement processing based on YOLO-v8 target detection model under MSRCR algorithm
Authors: Zhou Guoliang , Liu Min , Wang Hongxu , Zheng Yi 
Published: July 2024

Abstract
With the rapid development of the power industry, higher requirements have been put forward for real-time monitoring and fault identification of power equipment. However, images of power equipment in actual scenes are often affected by problems such as uneven illumination and color distortion, leading to a decrease in the performance of the target detection model. Hence, this paper suggests merging the Multi-Scale Retinex with Color Restoration (MSRCR) algorithm with the YOLO-v8 target detection model to enhance the visual quality of power equipment images and boost the accuracy and efficiency of target detection. Initially, the MSRCR algorithm enhances image brightness, contrast, and color restoration and preserves edge and detail features. Subsequently, the paper explores the architecture of YOLO-v8, incorporating the SE (Squeeze-and-Excitation) attention mechanism. This mechanism dynamically adjusts channel weights to optimize feature processing in input data. The final experimental results show that using the MSRCR algorithm to enhance the data and combining it with the SE attention mechanism have improved by about 3.2% compared to the original YOLO-v8 model. In comparative experiments with other algorithms, the method proposed in this article achieved an accuracy of 94.3% and a recall rate of 92.6%, which are both higher than other models. By enhancing power equipment images with the MSRCR algorithm, the YOLO-v8 model has significantly improved both target detection accuracy and recall rate. In summary, the MSRCR power equipment image enhancement processing method proposed in this article based on the YOLO-v8 target detection model can effectively improve the visual quality of power equipment images and improve the accuracy and efficiency of target detection.