bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of multiple treatment cycles with anti-CGRP monoclonal antibodies on migraine course: focus on discontinuation periods. Insights from the multicenter, prospective, I-GRAINE study
Authors: Barbanti Piero , Aurilia Cinzia , Egeo Gabriella , Proietti Stefania , Torelli Paola , d’Onofrio Florindo , Carnevale Antonio , Tavani Sofia , Orlando Bianca , Fiorentini Giulia , Colombo Bruno , Filippi Massimo , Bonassi Stefano , Cevoli Sabina ,   for the Italian Migraine Registry (I-GRAINE) study group
Published: February 2024

Abstract
Objectives
While a single 12-month treatment cycle (TrC) with anti-CGRP mAbs is not disease-modifying for most patients, there is limited understanding of the effects of multiple TrCs on migraine course. We evaluated whether a second TrC might modify the migraine course by comparing the occurrence of migraine relapse after discontinuation of the second TrC to that following the cessation of the first TrC.

Methods
In a real-life, multicenter, prospective study we considered all consecutive patients diagnosed with high-frequency episodic migraine (HFEM) or chronic migraine (CM) with > 3 treatment failures and treated with any anti-CGRP mAbs for ≥ 2 consecutive 12-month TrCs who were responders at week 12. The primary endpoint was the change in monthly migraine days (MMD) for HFEM or monthly headache days (MHD) for CM at the first month of treatment discontinuation after the second TrC (D2) compared to the first TrC (D1). Secondary endpoints included variations in monthly analgesic medications (MAM), Numeric Rating Scale (NRS), and Headache Impact Test (HIT-6) scores, ≥ 50%, ≥ 75%, and 100% response rates, and relapse from episodic migraine to CM and from no-medication overuse (MO) to MO at D2 vs. D1.

Results
One-hundred-seventy-eight patients completed two 12-month TrCs with anti-CGRP mAbs. At D2, patients experienced a significant reduction in MMD (– 0.6, p = 0.028), MHD (– 2.6, p < 0.001), monthly analgesic medications (– 2.0, p < 0.001), and HIT-6 score (– 2.2, p < 0.001) compared to D1, indicating improved effectiveness. The ≥ 50% response rate at weeks 45–48 during the first TrC was 95.5%, while at weeks 45–48 of the second TrC was 99.4%. Corresponding rates at D1 was 20.2% whereas at D2 was 51.6% (p < 0.0001). No statistical difference emerged in ≥ 75% and 100% responders. The relapse rate from episodic migraine to CM at D2 was lower than at D1 (12.3% vs 30.4%; p = 0.0002) Fewer patients experienced relapse from no-MO to MO at D2 compared to D1 (29.5% vs 68.7%; p = 0.00001).

Discussion
A second TrC with anti-CGRP mAbs demonstrated clinical improvements compared to the first one, as indicated by a milder migraine relapse at D2 compared to D1. Multiple TrCs with anti-CGRP mAbs could progressively modify migraine evolution by reducing CGRP-dependent neuroinflammatory nociceptive inputs to the brain.
Neuro-ophthalmic complications of modern anti-cancer drugs
Authors: Oskam Joshua A. , Danesh-Meyer Helen V. 
Published: February 2024

Abstract
Purpose
Targeted cancer therapies have been responsible for a dramatic shift in treatment strategies for cancer, and the number of drugs, classes, and indications are continually growing. Neuro-ophthalmic complications of these medications are an uncommon but important subset of adverse events which profoundly impact vision. This review aims to collate studies and reports of known neuro-ophthalmic complications of targeted therapies and describe their management.

Methods
The anti-cancer drugs included in the review were any drugs targeting specific molecules involved in the cancer disease process. PubMed, EMBASE, and Web of Science were searched using the generic names of each drug and keywords of neuro-ophthalmic conditions. The prescribing information published by the US Food and Drug Administration (FDA) for each drug was also reviewed.

Results
Several classes of targeted anti-cancer drugs were found to cause neuro-ophthalmic adverse effects. Immune checkpoint inhibitors are responsible for a raft of immune-related adverse events such as optic neuritis, ischemic optic neuropathy, PRES, and myasthenia gravis. Therapies with anti-VEGF activity can provoke posterior reversible leukoencephalopathy, which commonly presents with visual loss and can be fatal if not treated promptly. Inhibitors of BCR-ABL1, VEGF, ALK, and proteasomes have all been linked to optic nerve disorders which can have debilitating consequences for vision.

Conclusion
The neuro-ophthalmic complications of modern anti-cancer drugs can limit or necessitate the withdrawal of these life-prolonging medications. Ophthalmologists should be alert for neuro-ophthalmic complications in these medications to facilitate prompt diagnosis and treatment and reduce the risk of severe and permanent consequences.
Fibrosis and expression of extracellular matrix proteins in human interventricular septum in aortic valve stenosis and regurgitation
Authors: Sedmera David , Kvasilova Alena , Eckhardt Adam , Kacer Petr , Penicka Martin , Kocka Matej , Schindler Dana , Kaban Ron , Kockova Radka 
Published: February 2024

AbstractValvular heart disease leads to ventricular pressure and/or volume overload. Pressure overload leads to fibrosis, which might regress with its resolution, but the limits and details of this reverse remodeling are not known. To gain more insight into the extent and nature of cardiac fibrosis in valve disease, we analyzed needle biopsies taken from the interventricular septum of patients undergoing surgery for valve replacement focusing on the expression and distribution of major extracellular matrix protein involved in this process. Proteomic analysis performed using mass spectrometry revealed an excellent correlation between the expression of collagen type I and III, but there was little correlation with the immunohistochemical staining performed on sister sections, which included antibodies against collagen I, III, fibronectin, sarcomeric actin, and histochemistry for wheat germ agglutinin. Surprisingly, the immunofluorescence intensity did not correlate significantly with the gold standard for fibrosis quantification, which was performed using Picrosirius Red (PSR) staining, unless multiplexed on the same tissue section. There was also little correlation between the immunohistochemical markers and pressure gradient severity. It appears that at least in humans, the immunohistochemical pattern of fibrosis is not clearly correlated with standard Picrosirius Red staining on sister sections or quantitative proteomic data, possibly due to tissue heterogeneity at microscale, comorbidities, or other patient-specific factors. For precise correlation of different types of staining, multiplexing on the same section is the best approach.
Risk of atrial fibrillation development in adolescent patients with inflammatory bowel disease
Authors: El Amrousy Doaa , El Ashry Heba , Maher Sara , Hamza Mohamed , Hasan Samir 
Published: February 2024

AbstractThere is increasing evidence linking chronic inflammation to the initiation and continuation of atrial fibrillation (AF). Inflammatory bowel diseases (IBD), namely (Crohn’s disease (CD) and ulcerative colitis (UC), are chronic systemic inflammatory disorders with both intestinal and extra-intestinal manifestations. Atrial electromechanical delay (EMD) has been known as an early marker of AF. The objective of this study was to evaluate the atrial electromechanical properties in children and adolescents with IBD during remission. One hundred IBD patients aged 12–17 years (50 with CD and 50 with UC) in remission state and 100 healthy controls were recruited for the study. Atrial electromechanical properties were measured using transthoracic echocardiography, tissue Doppler imaging, and simultaneous surface ECG recording. Interatrial EMD, left intra-atrial, and right intra-atrial EMD were calculated. IBD patients in remission state have significantly prolonged left and right intra-atrial EMD and interatrial EMD compared to healthy controls (P = 0.03,P = 0.02, andP = 0.01 respectively). No statistical difference was observed between CD and UC in terms of inter- and intra-atrial EMDs. Conclusion: Atrial EMD is increased in pediatric patients with IBD indicating the increased risk of AF development. Measurement of atrial EMD parameters might be used to predict the risk of the development of AF in pediatric patients with IBD.What is Known:• There is increasing evidence linking chronic inflammation to the initiation and continuation of atrial fibrillation (AF).• Inflammatory bowel diseases are chronic systemic inflammatory disorders with both intestinal and extra-intestinal manifestations.• Atrial electromechanical delay (EMD) has been reported as an early marker of AF.What is New:• Atrial EMD is increased in pediatric patients with IBD indicating the increased risk of AF development.• Measurement of atrial EMD parameters might be used to predict the risk of the development of AF in pediatric patients with IBD.
An angiogenesis-associated gene-based signature predicting prognosis and immunotherapy efficacy of head and neck squamous cell carcinoma patients
Authors: Chen Bangjie , Han Yanxun , Sheng Shuyan , Deng Jianyi , Vasquez Emely , Yau Vicky , Meng Muzi , Sun Chenyu , Wang Tao , Wang Yu , Sheng Mengfei , Wu Tiangang , Wang Xinyi , Liu Yuchen , Lin Ning , Zhang Lei , Shao Wei 
Published: February 2024

Abstract
Objectives
To develop a model that can assist in the diagnosis and prediction of prognosis for head and neck squamous cell carcinoma (HNSCC).

Materials and methods
Data from TCGA and GEO databases were used to generate normalized gene expression data. Consensus Cluster Plus was used for cluster analysis and the relationship between angiogenesis-associated gene (AAG) expression patterns, clinical characteristics and survival was examined. Support vector machine (SVM) and least absolute shrinkage and selection operator (LASSO) analyzes and multiple logistic regression analyzes were performed to determine the diagnostic model, and a prognostic nomogram was constructed using univariate and multivariate Cox regression analyses. ESTIMATE, XCELL, TIMER, QUANTISEQ, MCPCOUNTER, EPIC, CIBERSORT-ABS, CIBERSORT algorithms were used to assess the immune microenvironment of HNSCC patients. In addition, gene set enrichment analysis, treatment sensitivity analysis, and AAGs mutation studies were performed. Finally, we also performed immunohistochemistry (IHC) staining in the tissue samples.

Results
We classified HNSCC patients into subtypes based on differences in AAG expression from TCGA and GEO databases. There are differences in clinical features, TME, and immune-related gene expression between two subgroups. We constructed a HNSCC diagnostic model based on nine AAGs, which has good sensitivity and specificity. After further screening, we constructed a prognostic risk signature for HNSCC based on six AAGs. The constructed risk score had a good independent prognostic significance, and it was further constructed into a prognostic nomogram together with age and stage. Different prognostic risk groups have differences in immune microenvironment, drug sensitivity, gene enrichment and gene mutation.

Conclusion
We have constructed a diagnostic and prognostic model for HNSCC based on AAG, which has good performance. The constructed prognostic risk score is closely related to tumor immune microenvironment and immunotherapy response.
Optimizing machine learning yield functions using query-by-committee for support vector classification with a dynamic stopping criterion
Authors: Shoghi Ronak , Morand Lukas , Helm Dirk , Hartmaier Alexander 
Published: February 2024

AbstractIn the field of materials engineering, the accurate prediction of material behavior under various loading conditions is crucial. Machine Learning (ML) methods have emerged as promising tools for generating constitutive models straight from data, capable of describing complex material behavior in a more flexible way than classical constitutive models. Yield functions, which serve as foundation of constitutive models for plasticity, can be properly described in a data-oriented manner using ML methods. However, the quality of these descriptions heavily relies on the availability of sufficient high-quality and representative training data that needs to be generated by fundamental numerical simulations, experiments, or a combination of both. The present paper addresses the issue of data selection, by introducing an active learning approach for Support Vector Classification (SVC) and its application in training an ML yield function with suitable data. In this regard, the Query-By-Committee (QBC) algorithm was employed, guiding the selection of new training data points in regions of the feature space where a committee of models shows significant disagreement. This approach resulted in a marked reduction in the variance of model predictions throughout the active learning process. It was also shown that the rate of decrease in the variance went along with an increase in the quality of the trained model, quantified by the Matthews Correlation Coefficient (MCC). This demonstrated the effectiveness of the approach and offered us the possibility to define a dynamic stopping criterion based on the variance in the committee results.
Optimal time of starting tocilizumab in acute phase of adult-onset Still’s disease and comparison of its efficacy with that of methotrexate: a case series and a review of the literature
Authors: Suzuki Satoshi , Kataoka Yuko , Otani Tomoya , Taniguchi Yukino , Ikeda Keigo , Tamura Naoto , Morimoto Shinji 
Published: February 2024

AbstractAdult-onset still’s disease is a rare condition that is generally treated by glucocorticoids. Importantly, due to the limited established treatments, glucocorticoid-refractory cases are particularly difficult to treat. Between December 2009 and August 2022, nine patients with adult-onset Still’s disease were treated with tocilizumab (tocilizumab group). The therapeutic efficacy and safety of tocilizumab initiation in the acute phase were evaluated in cases of initial onset and recurrence. We also compared the efficacy of tocilizumab with that of methotrexate (methotrexate group, n = 13), which has been the drug of choice for adjunctive therapy. Tocilizumab demonstrated the expected efficacy in all four patients who received it at relapse and in three of the five patients who received it at the initial onset. However, two patients developed macrophage activation syndrome following treatment. A comparison of treatment effects between the methotrexate and tocilizumab groups revealed that the ferritin and C-reactive protein levels, severity score, and glucocorticoid doses decreased over time in both groups; nonetheless, the tocilizumab group experienced a more stable effect. Tocilizumab is undoubtedly a valuable treatment option for adult-onset Still’s disease, especially when administered at relapse. This suggests that it shows both high safety and good efficacy. Nevertheless, a larger sample size is required to validate the efficacy and safety of tocilizumab compared with those of the existing alternatives.

Key Points

• We examined the significance of TCZ in terms of therapeutic efficacy, reduction in glucocorticoid usage, and safety in patients with AOSD.

•We compared the therapeutic efficacy of TCZ with that of MTX, which is often used to treat glucocorticoid-resistant AOSD.

•TCZ is undoubtedly a valuable treatment option for AOSD, especially when administered at relapse, suggesting both high safety and good efficacy.
Real-scale measurements of debris-flow run-ups
Authors: Nagl Georg , Hübl Johannes , Scheidl Christian 
Published: February 2024

AbstractRapid mass movements, such as debris flows, endanger alpine areas due to their destructive nature. In order to counteract these dangerous flows, it is necessary to design appropriate mitigation measures. A particular problem is the run-up of debris flows that impact on such structures. We provide in situ measurements of the run-up of three natural debrnis flows, each with multiple surges, in Gadria Creek, resulting from interaction with a mid-channel structure monitoring station. Four models were checked against data from other studies and the in situ measurements of the natural debris flows. The natural debris-flow measurements are all located in low Froude areas (Fr < 3) typical of Alpine granular debris flows. Sediment-laden pre-surges with Froude values greater than 2 produced the largest run-up factors in terms of run-up heights standardized to flow heights. Nevertheless, ensuing debris-flow surges exhibited a notable granular behavior and occurred at low Froude values. The findings indicate that the use of an energy conservation-based prediction model yields the most accurate estimates of the observed run-up factors. However, this smooth, gradual run-up can also be enhanced by preceding debris deposition and the formation of ramps. This can also prevent the formation of a reflection or shock wave, as assumed in models based on conservation of mass and momentum. These models have mainly overestimated the run-up factors of the observed debris flows.
Do sociodemographic factors play a role in the relation between COVID-19 infection and obesity? Findings from a cross-sectional study in eastern Oslo
Authors: Pereira Margarida 
Published: February 2024

Abstract
Aim
This study aims to assess the odds of having COVID-19 according to an individual’s weight status and to identify the sociodemographic factors associated with having COVID-19 in a sample of individuals residing in the eastern districts of Oslo.

Subject and methods
This is a cross-sectional study that uses primary survey data collected in six districts of Oslo in June 2021. Chi-square tests are used to test associations between sociodemographic variables and individuals with healthy weight vs overweight/obesity and those who reported having COVID-19 or not. Logistic regression models were computed to identify the sociodemographic factors associated with having COVID-19 (sex, age, educational level, income, employment status, district of residence and having been born in Norway) using body mass index and dichotomic and continuous variable.

Results
The percentage of COVID-19 cases was higher in individuals with overweight/obesity (5.9%) than in individuals with healthy weight (5.0%). Being a woman, with overweight/obesity, from a younger age group, unemployed and not having been born in Norway, increases the odds of having COVID-19.

Conclusion
More research on the relevance of sociodemographic factors in the association between weight status and COVID-19, together with biological aspects, is needed, to allow the identification and protection of groups at greater risk of infection.
Perceived social benefits and drawbacks of sea turtle conservation efforts in a globally important sea turtle rookery
Authors: Vieira Sara , Jiménez Victor , Ferreira-Airaud Betânia , Pina Antunes , Soares Venceslau , Tiwari Manjula , Teodósio Maria A. , Castilho Rita , Nuno Ana 
Published: February 2024

AbstractConservation interventions have wide-ranging social impacts - both positive and negative. Yet a limited understanding of how conservation initiatives affect people’s livelihoods often hinders our ability to learn from past efforts and design more effective and equitable conservation measures. This is particularly needed when there is a high degree of overlap between critical habitats and human activities or a high cultural and economic demand for products derived from the conservation target. Here, we explore the social impacts of sea turtle conservation initiatives implemented on São Tomé Island (Gulf of Guinea) as a case study and consider how these might enhance or hinder future efforts. Semi-structured interviews were conducted with key actors involved in the sea turtle trade in December 2014-February 2015 (prior to the implementation of key initiatives) and February-April 2022. Our findings suggest a clear reduction in the scale of the sea turtle trade and the number of main actors involved. However, most respondents previously involved in the trade had experienced economic displacement and several associated social impacts, such as the reduced ability to support family and friends and food insecurity, due to trade restrictions. Financial capital was the main barrier to transitioning to alternative livelihoods, followed by the lack of skills and peer pressure. Finally, this study highlights the importance of considering human dimensions during the planning and implementation phase of conservation actions and the need for more investment focused on the well-being of communities to ensure the long-term survival of endangered species.
Neutral and niche theory in community ecology: a framework for comparing model realism
Authors: Morrow Katie H. 
Published: February 2024

AbstractEcological neutral theory has been controversial as an alternative to niche theory for explaining community structure. Neutral theory, which explains community structure in terms of ecological drift, is frequently charged with being unrealistic, but commentators have usually not provided an account of theory or model realism. In this paper, I propose a framework for comparing the “realism” or accuracy of alternative theories within a domain with respect to the extent to which the theories abstract and idealize. Using this framework I argue, contrary to most previous commentators, that neutral and niche theories are similarly realistic. Realism cannot provide a basis for accepting or rejecting either type of theory; instead, community ecologists should continue working with a plurality of models. While theoretical unification may become possible, we should treat a plurality of complementary, partial models as the expected situation within community ecology.
Repositioning baloxavir marboxil as VISTA agonist that ameliorates experimental asthma
Authors: Di Jian-wen , Wang Yi-xin , Ma Rui-xue , Luo Zhi-jie , Chen Wen-ting , Liu Wan-mei , Yuan Ding-yi , Zhang Yu-ying , Wu Yin-hao , Chen Cai-ping , Liu Jun 
Published: February 2024

AbstractV-type immunoglobulin domain–containing suppressor of T-cell activation (VISTA), a novel negative checkpoint regulator, plays an essential role in allergic pulmonary inflammation in mice. Treatment with a VISTA agonistic antibody could significantly improve asthma symptoms. Thus, for allergic asthma treatment, VISTA targeting may be a compelling approach. In this study, we examined the functional mechanism of VISTA in allergic pulmonary inflammation and screened the FDA-approved drugs for VISTA agonists. By using mass cytometry (CyTOF), we found that VISTA deficiency primarily increased lung macrophage infiltration in the OVA-induced asthma model, accompanied by an increased proportion of M1 macrophages (CD11b+F4/80+CD86+) and a decreased proportion of M2 macrophages (CD11b+F4/80+CD206+). Further in vitro studies showed that VISTA deficiency promoted M1 polarization and inhibited M2 polarization of bone marrow–derived macrophages (BMDMs). Importantly, we discovered baloxavir marboxil (BXM) as a VISTA agonist by virtual screening of FDA-approved drugs. The surface plasmon resonance (SPR) assays revealed that BXM (KD = 1.07 µM) as well as its active form, baloxavir acid (BXA) (KD = 0.21 µM), could directly bind to VISTA with high affinity. Notably, treatment with BXM significantly ameliorated asthma symptoms, including less lung inflammation, mucus secretion, and the generation of Th2 cytokines (IL-5, IL-13, and IL-4), which were dramatically attenuated by anti-VISTA monoclonal antibody treatment. BXM administration also reduced the pulmonary infiltration of M1 macrophages and raised M2 macrophages. Collectively, our study indicates that VISTA regulates pulmonary inflammation in allergic asthma by regulating macrophage polarization and baloxavir marboxil, and an old drug might be a new treatment for allergic asthma through targeting VISTA.