bluuebunny/crossref_metadata_2025_split huggingface dataset:
Excellent Outcome for Pediatric Patients With High-Risk Hodgkin Lymphoma Treated With Brentuximab Vedotin and Risk-Adapted Residual Node Radiation
Authors: Metzger Monika L. , Link Michael P. , Billett Amy L. , Flerlage Jamie , Lucas John T. , Mandrell Belinda N. , Ehrhardt Matthew J. , Bhakta Nickhill , Yock Torunn I. , Friedmann Alison M. , de Alarcon Pedro , Luna-Fineman Sandra , Larsen Eric , Kaste Sue C. , Shulkin Barry , Lu Zhaohua , Li Chen , Hiniker Susan M. , Donaldson Sarah S. , Hudson Melissa M. , Krasin Matthew J. 
Published: April 2021

PURPOSE Brentuximab vedotin, an effective anti-CD30 antibody-drug conjugate approved for use in adults with classical Hodgkin lymphoma (HL), was introduced in this frontline trial to reduce prescribed radiation in children and adolescents with classical HL. METHODS Open-label, single-arm, multicenter trial for patients (age ≤ 18 years) with stage IIB, IIIB, or IV classical HL was conducted. Brentuximab vedotin replaced each vincristine in the OEPA/COPDac (vincristine, etoposide, prednisone, and doxorubicin/cyclophosphamide, vincristine, prednisone, and dacarbazine) regimen according to GPOH-HD2002 treatment group 3 (TG3); two cycles of AEPA and four cycles of CAPDac. Residual node radiotherapy (25.5 Gy) was given at the end of all chemotherapy only to nodal sites that did not achieve a complete response (CR) at the early response assessment (ERA) after two cycles of therapy. Primary objectives were to evaluate the safety and efficacy (complete remission at ERA) of this combination and the 3-year event-free (EFS) and overall survival (OS). The trials are registered at ClinicalTrials.gov (identifier: NCT01920932 ). RESULTS Of the 77 patients enrolled in the study, 27 (35%) achieved complete remission at ERA and were spared radiation. Patients who were irradiated received radiation to individual residual nodal tissue. At a median follow-up of 3.4 years, the 3-year EFS was 97.4% (SE 2.3%) and the OS was 98.7% (SE 1.6%). One irradiated patient experienced disease progression at the end of therapy and now remains disease free more than 6 years following salvage therapy, and one unexpected death occurred. Only 4% of patients experienced grade 3 neuropathy. CONCLUSION The integration of brentuximab vedotin in the frontline treatment of pediatric high-risk HL is highly tolerable, facilitated significant reduction in radiation exposure, and yielded excellent outcomes.
Financial Toxicity of Cancer Care: An Analysis of Financial Burden in Three Distinct Health Care Systems
Authors: Parikh Divya A. , Ragavan Meera , Dutta Ritika , Garnet Edwards Jeffrey , Dickerson James , Maitra Debeshi , Aggarwal Sangeeta , Lee Fa-Chyi , Patel Manali I. 
Published: April 2021

PURPOSE: The financial toxicity of cancer care is a source of significant distress for patients with cancer. The purpose of this study is to understand factors associated with financial toxicity in three distinct care systems. METHODS: We conducted a cross-sectional survey of patients in three care systems, Stanford Cancer Institute (SCI), VA Palo Alto Health Care System (VAPAHCS), and Santa Clara Valley Medical Center (SCVMC), from October 2017 to May 2019. We assessed demographic factors, employment status, and out-of-pocket costs (OOPCs) and administered the validated COmprehensive Score for financial Toxicity tool. We calculated descriptive statistics and conducted linear regression models to analyze factors associated with financial toxicity. RESULTS: Four hundred forty-four of 578 patients (77%) completed the entire COmprehensive Score for financial Toxicity tool and were included in the analysis. Most respondents at SCI were White, with annual household income (AHI) > $50,000 USD and Medicare insurance. At the VAPAHCS, most were White, with AHI ≤ $50,000 USD and insured by the Veterans Administration. At SCVMC, most were Asian and/or Pacific Islander, with AHI ≤ $25,000 USD and Medicaid insurance. Low AHI ( P < .0001), high OOPCs ( P = .003), and employment changes as a result of cancer diagnosis ( P < .0001) were associated with financial toxicity in the pooled analysis. There was variation in factors associated with financial toxicity by site, with employment changes significant at SCI, OOPCs at SCVMC, and no significant factors at the VAPAHCS. CONCLUSION: Low AHI, high OOPCs, and employment changes contribute to financial toxicity; however, there are variations based on site of care. Future studies should tailor financial toxicity interventions within care delivery systems.
Estrous Cycle Plasticity in the Central Clock Output to Kisspeptin Neurons: Implications for the Preovulatory Surge
Authors: Jamieson Bradley B , Bouwer Gregory T , Campbell Rebecca E , Piet Richard 
Published: April 2021

Abstract
Coordination of ovulation and behavior is critical to reproductive success in many species. During the female estrous cycle, the preovulatory gonadotropin surge occurs when ovarian follicles reach maturity and, in rodents, it begins just before the daily onset of activity, ensuring that ovulation coincides with sex behavior. Timing of the surge relies on projections from the suprachiasmatic nucleus (SCN), the locus of the central circadian clock, to hypothalamic circuits that regulate gonadotropin secretion. The cellular mechanisms through which the SCN controls these circuits and gates the preovulatory surge to the appropriate estrous cycle stage, however, are poorly understood. We investigated in mice the functional impact of SCN arginine-vasopressin (AVP) neuron projections to kisspeptin (Kiss1) neurons in the rostral periventricular area of the third ventricle (RP3VKiss1), responsible for generating the preovulatory surge. Conditional anterograde tracing revealed that SCNAVP neurons innervate approximately half of the RP3VKiss1 neurons. Optogenetic activation of SCNAVP projections in brain slices caused an AVP-mediated stimulation of RP3VKiss1 action potential firing in proestrus, the cycle stage when the surge is generated. This effect was less prominent in diestrus, the preceding cycle stage, and absent in estrus, following ovulation. Remarkably, in estrus, activation of SCNAVP projections resulted in GABA-mediated inhibition of RP3VKiss1 neuron firing, an effect rarely encountered in other cycle stages. Together, these data reveal functional plasticity in SCNAVP neuron output that drives opposing effects on RP3VKiss1 neuron activity across the ovulatory cycle. This might contribute to gating activation of the preovulatory surge to the appropriate estrous cycle stage.
Unexpected lack of specialisation in the flow properties of spitting cobra venom
Authors: Avella Ignazio , Barajas-Ledesma Edgar , Casewell Nicholas R. , Harrison Robert A. , Rowley Paul D. , Crittenden Edouard , Wüster Wolfgang , Castiglia Riccardo , Holland Chris , van der Meijden Arie 
Published: April 2021

ABSTRACT
Venom spitting is a defence mechanism based on airborne venom delivery used by a number of different African and Asian elapid snake species (‘spitting cobras’; Naja spp. and Hemachatus spp.). Adaptations underpinning venom spitting have been studied extensively at both behavioural and morphological level in cobras, but the role of the physical properties of venom itself in its effective projection remains largely unstudied. We hereby provide the first comparative study of the physical properties of venom in spitting and non-spitting cobras. We measured the viscosity, protein concentration and pH of the venom of 13 cobra species of the genus Naja from Africa and Asia, alongside the spitting elapid Hemachatus haemachatus and the non-spitting viper Bitis arietans. By using published microCT scans, we calculated the pressure required to eject venom through the fangs of a spitting and a non-spitting cobra. Despite the differences in the modes of venom delivery, we found no significant differences between spitters and non-spitters in the rheological and physical properties of the studied venoms. Furthermore, all analysed venoms showed a Newtonian flow behaviour, in contrast to previous reports. Although our results imply that the evolution of venom spitting did not significantly affect venom viscosity, our models of fang pressure suggests that the pressure requirements to eject venom are lower in spitting cobras than in non-spitting cobras.
Chemotherapy After Diagnosis of Malignant Bowel Obstruction is Associated with Superior Survival for Medicare Patients with Advanced Malignancy
Authors: Bateni Sarah B. , Gingrich Alicia A. , Kirane Amanda R. , Sauder Candice A. M. , Gholami Sepideh , Bold Richard J. , Meyers Frederick J. , Canter Robert J. 
Published: April 2021

AbstractBackgroundAlthough malignant bowel obstruction (MBO) often is a terminal event, systemic therapies are advocated for select patients to extend survival. This study aimed to evaluate factors associated with receipt of chemotherapy after MBO and to determine whether chemotherapy after MBO is associated with survival.MethodsThis retrospective cohort study investigated patients 65 years of age or older with metastatic gastrointestinal, gynecologic, or genitourinary cancers who were hospitalized with MBO from 2008 to 2012 using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Fine and Gray models were used to identify factors associated with receipt of chemotherapy accounting for the competing risk of death. Cox models identified factors associated with overall survival.ResultsOf the 2983 MBO patients, 39% (n= 1169) were treated with chemotherapy after MBO. No differences in receipt of chemotherapy between the surgical and medical patients were found in the univariable analysis (subdistribution hazard ratio [SHR], 0.96; 95% confidence interval [CI], 0.86–1.07;p= 0.47) or multivariable analysis (SHR, 1.12; 95% CI, 1.00–1.26;p= 0.06). Older age, African American race, medical comorbidities, non-colorectal and non-ovarian cancer diagnoses, sepsis, ascites, and intensive care unit stays were inversely associated with receipt of chemotherapy after MBO (p< 0.05). Chemotherapy with surgery was associated with longer survival than surgery (adjusted hazard ratio [aHR], 2.97; 95% CI, 2.65–3.34;p< 0.01) or medical management without chemotherapy (aHR, 4.56; 95% CI, 4.04–5.14;p< 0.01). Subgroup analyses of biologically diverse cancers (colorectal, pancreatic, and ovarian) showed similar results, with greater survival related to chemotherapy (p< 0.05).ConclusionsChemotherapy plays an integral role in maximizing oncologic outcome for select patients with MBO. The data from this study are critical to optimizing multimodality care for these complex patients.
Doctoral Studies as part of an Innovative Training Network (ITN): Early Stage Researcher (ESR) experiences
Authors: Biswas Roshni , Schiller Axel , Casolani Chiara , Daoud Elza , Dode Albi , Genitsaridi Eleni , Jacquemin Laure , Liyanage Nuwan , Lourenco Matheus , Makani Punitkumar , Parameshwarappa Vinay , Riha Constanze , L Santacruz Jose , Shabbir Maryam , Simoes Jorge , Trpchevska Natalia , Schoisswohl Stefan 
Published: April 2021

Background: The Marie-Skłodowska-Curie Actions’ (MSCA) Innovative Training Network (ITN) is a doctoral training programme jointly implemented by academic institutions and industries from countries across Europe and beyond. To our knowledge no study has examined the experience of students participating in MSCA-ITNs. This study aims to evaluate and report MSCA-ITN Early Stage Researcher (ESR) experiences. Methods: The Innovative Training Network - Evaluation Questionnaire (ITN-EQ) was developed to assess supervision, training, collaborations and experiences of ESRs and forwarded to two tinnitus-related ITNs and seven ITNs of other disciplines. Results: Key advantages identified included better career prospects, multidisciplinary research opportunities/ collaborations, international exposure, personal/ professional development, plus generous salaries and research budgets. However, lack of a common EU framework resulted in the experience being largely dependent on host institution, country and supervisor. Moreover, managing the dual requirements of ITNs and host institutions while completing a three-year PhD seemed challenging for most ESRs. ESR involvement in workshop and training school planning was desirable. More than 80% of ESRs rated the overall ITN experience favourably and 98.3% would recommend the same to prospective PhD students. Conclusions: This report could provide valuable insights in planning and management of future ITNs and could assist prospective students in their decision of joining an ITN for their PhD.
Composite and bonding agent sensitivity in orthodontics
Authors: Wong Lilia , Patel Sameer , Christensen Lars 
Published: April 2021

The nature of the type of treatment carried out in orthodontics frequently exposes clinical staff to potential occupational hazards. A lesser-known risk includes hypersensitivity to composite resins and bonding materials, as well as the permeability of gloves to these materials. This article highlights the importance of care when handling composite materials, and suggests methods to reduce potential exposure. CPD/Clinical Relevance: Composite and bonding agents are frequently used in orthodontics; however, adverse effects resulting from exposure are not commonly discussed. This paper aims to increase awareness and provide practical methods of reducing risk.
Idiopathic condylar resorption in orthodontics
Authors: El-Habbash Salwa , McSwiney Timothy 
Published: April 2021

Condylar resorption (CR) can be categorized into functional and dysfunctional remodelling of the temporomandibular joint (TMJ). The literature describes dysfunctional remodelling of the TMJ as idiopathic condylar resorption (ICR). Idiopathic condylar resorption (ICR) is a well-documented but poorly understood pathological entity that can occur spontaneously or post-orthognathic surgery. It predominantly affects young women, with other risk factors including Class 2 malocclusion with steep mandibular plane angles. It is distinguished by a decreased condylar head volume and ramus height, progressive mandibular retrusion and an anterior open bite. Its aetiology can be categorized into surgical and non-surgical risk factors. These include hormones, systemic disease, trauma, mechanical load and surgical risk factors, such as magnitude and direction of mandibular movement, type of surgical fixation and length of post-operative maxilla-mandibular fixation. ICR is a diagnosis of exclusion, and identified by a combination of clinical, radiographic and haematological findings. Multiple treatment options have been described in the literature, including medical management, orthodontics, orthognathic surgery, TMJ surgery, TMJ and orthognathic surgery combined, and total joint prosthesis reconstruction. Further research is required to better understand the aetiology of ICR and more long-term, controlled, multicentre clinical studies are needed to evaluate the outcomes of surgical and non-surgical management of CR patients. CPD/Clinical Relevance: Idiopathic condylar resorption has many presentations and potential causes that can greatly impact the decisions and outcomes for orthodontic/orthognathic treatment.
Growth modulation of angular deformities with a novel constant force implant concept-preclinical results
Authors: Buschbaum Jan , Freitag Linda , Slongo Theodor F. , Zeiter Stephan , Schütz Michael , Windolf Markus 
Published: April 2021

Purpose Varus-valgus deformities in children and adolescents are often corrected by temporary hemi-epiphysiodesis, in which the physis is bridged by an implant to inhibit growth. With standard implant solutions, the acting forces cannot be regulated, rendering the correction difficult to control. Furthermore, the implant load steadily increases with ongoing growth potentially leading to implant-related failures. A novel implant concept was developed applying a controlled constant force to the physis, which carries the potential to avoid these complications. The study aim was to proof the concept in vivo by analyzing the effect of three distinct force levels on the creation of varus deformities. Methods The proposed implant is made of a conventional cerclage wire and features a twisted coil that unwinds with growth resulting in an implant-specific constant force level. The proximal medial tibial physes of 18 lambs were treated with the implant and assigned to three groups distinct by the force level of the implant (200 N, 120 N, 60 N). Results The treatment appeared safe without implant-related failures. Deformity creation was statistically different between the groups and yielded on average 10.6° (200 N), 4.8° (120 N) and 0.4° (60 N) over the treatment period. Modulation rates were 0.51°/mm (200 N), 0.23°/mm (120 N) and 0.05°/mm (60 N) and were constant throughout the treatment. Conclusion By means of the constant force concept, controlled growth modulation appeared feasible in this preclinical experiment. However, clinical trials are necessary to confirm whether the results are translatable to the human pathological situation.
Modified Firefly Algorithm and Fuzzy C-Mean Clustering Based Semantic Information Retrieval
Authors: Subramaniam M. , Kathirvel A. , Sabitha E. , Anwar Basha H. 
Published: April 2021

As enormous volume of electronic data increased gradually, searching as well as retrieving essential info from the internet is extremely difficult task. Normally, the Information Retrieval (IR) systems present info dependent upon the user’s query keywords. At present, it is insufficient as large volume of online data and it contains less precision as the system takes syntactic level search into consideration. Furthermore, numerous previous search engines utilize a variety of techniques for semantic based document extraction and the relevancy between the documents has been measured using page ranking methods. On the other hand, it contains certain problems with searching time. With the intention of enhancing the query searching time, the research system implemented a Modified Firefly Algorithm (MFA) adapted with Intelligent Ontology and Latent Dirichlet Allocation based Information Retrieval (IOLDAIR) model. In this recommended methodology, the set of web documents, Face book comments and tweets are taken as dataset. By means of utilizing Tokenization process, the dataset pre-processing is carried out. Strong ontology is built dependent upon a lot of info collected by means of referring via diverse websites. Find out the keywords as well as carry out semantic analysis with user query by utilizing ontology matching by means of jaccard similarity. The feature extraction is carried out dependent upon the semantic analysis. After that, by means of Modified Firefly Algorithm (MFA), the ideal features are chosen. With the help of Fuzzy C-Mean (FCM) clustering, the appropriate documents are grouped and rank them. At last by using IOLDAIR model, the appropriate information’s are extracted. The major benefit of the research technique is the raise in relevancy, capability of dealing with big data as well as fast retrieval. The experimentation outcomes prove that the presented method attains improved performance when matched up with the previous system.
The global governance on automated facial recognition (AFR): ethical and legal opportunities and privacy challenges
Authors: Bu Qingxiu 
Published: April 2021

AbstractThe digital revolution transforms people’s view about values and priorities. Automated facial recognition (AFR) comes with many concerns as well as benefits. The technology raises significant legal and ethical challenges, which risk perpetuating systemic injustice unless countervailing measures are put in place. The way facial images are obtained and used, potentially without consent or opportunities to opt out, can have a negative impact on people’s privacy. Laws on privacy vary across jurisdictions, which has an enormous effect on measures that could be taken to safeguard AFR-related ethical concerns. In an era of digitalisation, the existing laws are ill-equipped to address evolving needs against threats to individual privacy. Integrating the principles of proportionality and necessity, of the upmost importance is to ensure the proper use of AFR in a socially responsible way. It is imperative to build an AFR infrastructure that incorporates society’s legal and ethical commitments, and further address the challenges of governing the technology.
An update on the occurrence of Paracoccidioides species in the Midwest region, Brazil: Molecular epidemiology, clinical aspects and serological profile of patients from Mato Grosso do Sul State
Authors: Mattos Karine , Cocio Tiago Alexandre , Chaves Edilânia Gomes Araújo , Borges Clayton Luiz , Venturini James , de Carvalho Lídia Raquel , Mendes Rinaldo Poncio , Paniago Anamaria Mello Miranda , Weber Simone Schneider 
Published: April 2021

Background
Paracoccidioidomycosis (PCM) is a systemic and endemic fungal infection in Latin American, mainly in Brazil. The majority of PCM cases occur in large areas in Brazil, comprising the South, Southeast and Midwest regions, with the latter demonstrating a higher incidence of the species Paracoccidioides lutzii.

Methodology and main findings
This study presents clinical, molecular and serological data of thirteen new PCM cases during 2016 to 2019 from the state of Mato Grosso do Sul, located in the Midwest region, Brazil. From these thirteen cases, sixteen clinical isolates were obtained and their genomic DNAs were subjected to genotyping by tub1 -PCR-RFLP. Results showed Paracoccidioides brasiliensis sensu stricto (S1) (11/16; 68.8%), Paracoccidioides restrepiensis (PS3) (4/16; 25.0%) and P. lutzii (1/16; 6.2%) as Paracoccidiodes species. Therefore, in order to understand whether the type of phylogenetic species that are circulating in the state influence the reactivity profile of serological tests, we performed double agar gel immunodiffusion (DID), using exoantigens from genotyped strains found in this series of PCM cases. Overall, our DID tests have been false negative in about 30% of confirmed PCM cases. All patients were male, most with current or previous rural activity, with ages ranging from 17 to 59 years, with 11 patients (84.6%) over 40 years of age. No clinical or epidemiological differences were found between Paracoccidioides species. However, it is important to note that the only case of P. lutzii died as an outcome.

Conclusions
This study suggests P. brasiliensis sensu stricto (S1) as the predominant species, showing its wide geographic distribution in Brazil. Furthermore, our findings revealed, for the first time, the occurrence of P. restrepiensis (PS3) in the state of Mato Grosso do Sul, Brazil. Despite our setbacks, it would be interesting to provide the complete sequencing of these clinical isolates to complement the molecular information presented.