bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pigmented nonmelanoma skin cancers of the genital area: a diagnostic and therapeutic challenge – monocentric experience and review of the literature
Authors: Licata Gaetano , Tancredi Vittorio , Giorgio Caterina M. , Arisi Mariachiara , Damiani Luca , Benvenuto Pierfrancesco , Moscarella Elvira , Argenziano Giuseppe 
Published: June 2024

AbstractNonmelanoma skin cancers (NMSC), comprising basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), are typically encountered on photo‐exposed skin. Nevertheless, several cases of NMSC have been described in covered areas such as the genital region; furthermore, some of these lesions may express a variable degree of pigmentation. Due to the existence of mucosal melanoma, an accurate diagnosis is paramount. In this narrative review, we focused our attention on management and – in particular‐ diagnosis of pigmented NMSC (pNMSC) located in the genital region, emphasizing the features assessed by dermoscopy and reflectance confocal microscopy. As an implementation, we included data on pNMSC from the Dermatology Unit of the University of Campania Vanvitelli. BCC in the genital region represents only 1% of all BCC cases. It has been supposed that the mutation of patched 1 may lead to the development of BCC even without concomitant UV exposure. Pigmented variants on genitals have seldom been described. More prominent dermoscopic features seem to be blue‐gray ovoid nests and arborizing vessels associated with whitish structureless areas. SCC and Bowen's disease (BD) – a variant of in situ SCC – may be encountered in the genital area and are sometimes associated with human papillomavirus (HPV) infection. Pigmented SCC is very rare, and most of the literature is focused on pigmented BD (pBD), which is mainly characterized by gray‐brown dots in a linear fashion and glomerular vessels without evident scales. In conclusion, pNMSC is rarely encountered on genitals; evaluation with dermoscopy or other ancillary devices like RCM is important both to exclude benign lesions like seborrheic keratosis and lentigo and to rule out melanoma.
Patient‐reported outcomes and treatment adherence in type 2 diabetes using natural language processing: Wave 8 of the Observational International Diabetes Management Practices Study
Authors: Chan Juliana CN , Mbanya Jean Claude , Chantelot Jean‐Marc , Shestakova Marina , Ramachandran Ambady , Ilkova Hasan , Deplante Lucille , Rollot Melissa , Melas‐Melt Lydie , Gagliardino Juan Jose , Aschner Pablo 
Published: June 2024

AbstractAims/IntroductionWe analyzed patient‐reported outcomes of people with type 2 diabetes to better understand perceptions and experiences contributing to treatment adherence.Materials and MethodsIn the ongoing International Diabetes Management Practices Study, we collected patient‐reported outcomes data from structured questionnaires (chronic treatment acceptance questionnaire and Diabetes Self‐Management Questionnaire) and free‐text answers to open‐ended questions to assess perceptions of treatment value and side‐effects, as well as barriers to, and enablers for, adherence and self‐management. Free‐text answers were analyzed by natural language processing.ResultsIn 2018–2020, we recruited 2,475 patients with type 2 diabetes (43.3% insulin‐treated, glycated hemoglobin (HbA1c) 8.0 ± 1.8%; 30.9% with HbA1c <7%) from 13 countries across Africa, the Middle East, Europe, Latin America and Asia. Mean ± standard deviation scores of chronic treatment acceptance questionnaire (acceptance of medication, rated out of 100) and Diabetes Self‐Management Questionnaire (self‐management, rated out of 10) were 87.8 ± 24.5 and 3.3 ± 0.9, respectively. Based on free‐text analysis and coded responses, one in three patients reported treatment non‐adherence. Overall, although most patients accepted treatment values and side‐effects, self‐management was suboptimal. Treatment duration, regimen complexity and disruption of daily routines were major barriers to adherence, whereas habit formation was a key enabler. Treatment‐adherent patients were older (60 ± 11.6 vs 55 ± 11.7 years, P < 0.001), and more likely to have longer disease duration (12 ± 8.6 vs 10 ± 7.7 years, P < 0.001), exposure to diabetes education (73.1% vs 67.8%, P < 0.05), lower HbA1c (7.9 ± 1.8% vs 8.3 ± 1.9%, P < 0.001) and attainment of HbA1c <7% (29.7% vs 23.3%, P < 0.01).ConclusionsPatient perceptions/experiences influence treatment adherence and self‐management. Patient‐centered education and support programs that consider patient‐reported outcomes aimed at promoting empowerment and developing new routines might improve glycemic control.
Sensemaking of Process Data from Evaluation Studies of Educational Games: An Application of Cross‐Classified Item Response Theory Modeling
Authors: Feng Tianying , Cai Li 
Published: June 2024

AbstractProcess information collected from educational games can illuminate how students approach interactive tasks, complementing assessment outcomes routinely examined in evaluation studies. However, the two sources of information are historically analyzed and interpreted separately, and diagnostic process information is often underused. To tackle these issues, we present a new application of cross‐classified item response theory modeling, using indicators of knowledge misconceptions and item‐level assessment data collected from a multisite game‐based randomized controlled trial. This application addresses (a) the joint modeling of students' pretest and posttest item responses and game‐based processes described by indicators of misconceptions; (b) integration of gameplay information when gauging the intervention effect of an educational game; (c) relationships among game‐based misconception, pretest initial status, and pre‐to‐post change; and (d) nesting of students within schools, a common aspect in multisite research. We also demonstrate how to structure the data and set up the model to enable our proposed application, and how our application compares to three other approaches to analyzing gameplay and assessment data. Lastly, we note the implications for future evaluation studies and for using analytic results to inform learning and instruction.
Spatial and spatiotemporal volatility models: A review
Authors: Otto Philipp , Doğan Osman , Taşpınar Süleyman , Schmid Wolfgang , Bera Anil K. 
Published: June 2024

AbstractSpatial and spatiotemporal volatility models are a class of models designed to capture spatial dependence in the volatility of spatial and spatiotemporal data. Spatial dependence in the volatility may arise due to spatial spillovers among locations; that is, in the case of positive spatial dependence, if two locations are in close proximity, they can exhibit similar volatilities. In this paper, we aim to provide a comprehensive review of the recent literature on spatial and spatiotemporal volatility models. We first briefly review time series volatility models and their multivariate extensions to motivate their spatial and spatiotemporal counterparts. We then review various spatial and spatiotemporal volatility specifications proposed in the literature along with their underlying motivations and estimation strategies. Through this analysis, we effectively compare all models and provide practical recommendations for their appropriate usage. We highlight possible extensions and conclude by outlining directions for future research.
Discovery of a novel symbiotic lineage associated with a hematophagous leech from the genus
Haementeria
Authors: Sosa-Jiménez Víctor Manuel , Kvist Sebastian , Manzano-Marín Alejandro , Oceguera-Figueroa Alejandro 
Published: June 2024

ABSTRACT

Similarly to other strict blood feeders, leeches from the
Haementeria
genus (Hirudinida: Glossiphoniidae) have established a symbiotic association with bacteria harbored intracellularly in esophageal bacteriomes. Previous genome sequence analyses of these endosymbionts revealed co-divergence with their hosts, a strong genome reduction, and a simplified metabolism largely dedicated to the production of B vitamins, which are nutrients lacking from a blood diet. ‘
Candidatus
Providencia siddallii‘ has been identified as the obligate nutritional endosymbiont of a monophyletic clade of Mexican and South American
Haementeria
spp. However, the
Haementeria
genus includes a sister clade of congeners from Central and South America, where the presence or absence of the aforementioned symbiont taxon remains unknown. In this work, we report on a novel bacterial endosymbiont found in a representative from this
Haementeria
clade. We found that this symbiont lineage has evolved from within the
Pluralibacter
genus, known mainly from clinical but also environmental strains. Similarly to
Ca
.
Providencia siddallii
, the
Haementeria
-associated
Pluralibacter
symbiont displays clear signs of genome reduction, accompanied by an A+T-biased sequence composition. Genomic analysis of its metabolic potential revealed a retention of pathways related to B vitamin biosynthesis, supporting its role as a nutritional endosymbiont. Finally, comparative genomics of both
Haementeria
symbiont lineages suggests that an ancient
Providencia
symbiont was likely replaced by the novel
Pluralibacter
one, thus constituting the first reported case of nutritional symbiont replacement in a leech without morphological changes in the bacteriome.

IMPORTANCE

Obligate symbiotic associations with a nutritional base have likely evolved more than once in strict blood-feeding leeches. Unlike those symbioses found in hematophagous arthropods, the nature, identity, and evolutionary history of these remains poorly studied. In this work, we further explored obligate nutritional associations between
Haementeria
leeches and their microbial symbionts, which led to the unexpected discovery of a novel symbiosis with a member of the
Pluralibacter
genus. When compared to
Providencia siddallii
, an obligate nutritional symbiont of other
Haementeria
leeches, this novel bacterial symbiont shows convergent retention of the metabolic pathways involved in B vitamin biosynthesis. Moreover, the genomic characteristics of this
Pluralibacter
symbiont suggest a more recent association than that of
Pr. siddallii
and
Haementeria
. We conclude that the once-thought stable associations between blood-feeding Glossiphoniidae and their symbionts (i.e., one bacteriome structure, one symbiont lineage) can break down, mirroring symbiont turnover observed in various arthropod lineages.
Using the Translating Research into Practice framework to develop a diabetes prevention intervention in primary care: a mixed-methods study
Authors: Tseng Eva , Smith Katherine , Clark Jeanne M , Segal Jodi B , Marsteller Jill A , Maruthur Nisa M 
Published: June 2024

BackgroundPre-diabetes affects one-third of US adults and increases the risk of type 2 diabetes. Effective evidence-based interventions, such as the Diabetes Prevention Program, are available, but a gap remains in effectively translating and increasing uptake of these interventions into routine care.MethodsWe applied the Translating Research into Practice (TRiP) framework to guide three phases of intervention design and development for diabetes prevention: (1) summarise the evidence, (2) identify local barriers to implementation and (3) measure performance. In phase 1, we conducted a retrospective cohort analysis of linked electronic health record claims data to evaluate current practices in the management of pre-diabetes. In phase 2, we conducted in-depth interviews of 16 primary care physicians, 7 payor leaders and 31 patients to elicit common barriers and facilitators for diabetes prevention. In phase 3, using findings from phases 1 and 2, we developed the core elements of the intervention and performance measures to evaluate intervention uptake.ResultsIn phase 1 (retrospective cohort analysis), we found few patients with pre-diabetes received diabetes prevention interventions. In phase 2 (stakeholder engagement), we identified common barriers to include a lack of knowledge about pre-diabetes among patients and about the Diabetes Prevention Program among clinicians. In phase 3 (intervention development), we developed the START Diabetes Prevention Clinical Pathway as a systematic change package to address barriers and facilitators identified in phases 1 and 2, performance measures and a toolkit of resources to support the intervention components.ConclusionsThe TRiP framework supported the identification of evidence-based care practices for pre-diabetes and the development of a well-fitted, actionable intervention and implementation plan designed to increase treatment uptake for pre-diabetes in primary care settings. Our change package can be adapted and used by other health systems or clinics to target prevention of diabetes or other related chronic conditions.
Prevalence and outcomes of patients with SMuRF-less acute coronary syndrome undergoing percutaneous coronary intervention
Authors: Ball Jocasta , Dinh Diem T , Brennan Angela , Ajani Andrew , Clark David J , Freeman Melanie , Oqueli Ernesto , Hiew Chin , Nanayakkara Shane , Walton Antony , Shaw James A , Chan William , Reid Christopher M , Stub Dion 
Published: June 2024

BackgroundThere is increasing awareness that patients without standard modifiable risk factors (SMuRFs; diabetes, hypercholesterolaemia, hypertension and smoking) may represent a unique subset of patients with acute coronary syndrome (ACS). We aimed to investigate the prevalence and outcomes of patients with SMuRF-less ACS undergoing percutaneous coronary intervention (PCI) compared with those with SMuRFs.MethodsWe analysed data from the Melbourne Interventional Group PCI Registry. Patients with coronary artery disease were excluded. The primary outcome was 30-day mortality. Secondary outcomes included in-hospital and 30-day events. Long-term mortality was investigated using Cox-proportional hazards regression.ResultsFrom 1 January 2005 to 31 December 2020, 2727/18 988 (14.4%) patients were SMuRF less, with the proportion increasing over time. Mean age was similar for patients with and without SMuRFs (63 years), and fewer females were SMuRF-less (19.8% vs 25.4%, p<0.001). SMuRF-less patients were more likely to present with cardiac arrest (6.6% vs 3.9%, p<0.001) and ST-elevation myocardial infarction (59.1% vs 50.8%, p<0.001) and were more likely to experience postprocedural cardiogenic shock (4.5% vs 3.6%, p=0.019) and arrhythmia (11.2% vs 9.9%, p=0.029). At 30 days, mortality, myocardial infarction, revascularisation and major adverse cardiac and cerebrovascular events did not differ between the groups. During median follow-up of 7 years, SMuRF-less patients had an adjusted 13% decreased rate of mortality (HR 0.87 (95% CI 0.78 to 0.97)).ConclusionsThe proportion of SMuRF-less patients increased over time. Presentation was more often a devastating cardiac event compared with those with SMuRFs. No difference in 30-day outcomes was observed and SMuRF-less patients had lower hazard for long-term mortality.
Abstract A014: Inhibiting eIF4E phosphorylation sensitizes triple-negative breast cancer to CDK4/6 inhibition
Authors: Deng Qiyun , Amiri Mehdi , Piric Anastasija Ana , Bagherian Yasaman , Li Zilan , Huang Sidong , Pollak Michael , Sonenberg Nahum 
Published: June 2024

Abstract
This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR011) of the Conference Program/Proceedings.
Citation Format: Qiyun Deng, Mehdi Amiri, Anastasija Ana Piric, Yasaman Bagherian, Zilan Li, Sidong Huang, Michael Pollak, Nahum Sonenberg. Inhibiting eIF4E phosphorylation sensitizes triple-negative breast cancer to CDK4/6 inhibition [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities; 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr A014.
Abstract B015: Combinatorial genetic screens to map synthetic lethal interactions and identify new cancer drug targets in KRAS mutant cancers
Authors: Arafeh Rand , Chang Laura , Sawyer Lydia , Wang Helen , McFarland James , Dempster Joshua , DeWeirdt Peter , Doench John , Hahn William C 
Published: June 2024

Abstract
This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR014) of the Conference Program/Proceedings.
Citation Format: Rand Arafeh, Laura Chang, Lydia Sawyer, Helen Wang, James McFarland, Joshua Dempster, Peter DeWeirdt, John Doench, William C Hahn. Combinatorial genetic screens to map synthetic lethal interactions and identify new cancer drug targets in KRAS mutant cancers [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities; 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr B015.
Abstract B020: Novel WRN helicase inhibitors selectively target microsatellite unstable cancer cells
Authors: Picco Gabriele , Rao Yanhua , Al Saedi Angham , Lee Yang , Bhosle Shriram , Herranz-Ors Carmen , Walker Samantha , May Kieron , Coelho Matthew , Houseley Jon , Schwartz Benjamin , Garnett Mathew J. 
Published: June 2024

Abstract
Microsatellite-unstable (MSI) cancers require WRN helicase to resolve replication stress due to expanded DNA (TA)n-dinucleotide repeats. WRN is a promising synthetic lethal target for MSI tumours, and WRN inhibitors are in development. Here, we used CRISPR-Cas9 base editing to map WRN residues critical for MSI cells, validating the helicase domain as the primary drug target. Fragment-based screening led to the development of potent and highly selective WRN helicase covalent inhibitors. These compounds selectively suppressed MSI model growth In vitro and In vivo by mimicking WRN loss, inducing DNA double-strand breaks at expanded TA-repeats and DNA damage. Assessment of biomarkers in preclinical models linked TA-repeat expansions and mismatch repair (MMR) alterations to compound activity. Efficacy was confirmed in immunotherapy-resistant organoids and patient-derived xenograft (PDX) models. The discovery of potent, selective covalent WRN inhibitors provides proof of concept for synthetic-lethal targeting of WRN in MSI cancer and tools to dissect WRN biology.
Citation Format: Gabriele Picco, Yanhua Rao, Angham Al Saedi, Yang Lee, Shriram Bhosle, Carmen Herranz-Ors, Samantha Walker, Kieron May, Matthew Coelho, Jon Houseley, Benjamin Schwartz, Mathew J. Garnett. Novel WRN helicase inhibitors selectively target microsatellite unstable cancer cells [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities; 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr B020.
Abstract IA002: Overcoming the K-Ras inhibitor resistant cell state in PDAC with molecular glues.
Authors: Ferguson Fleur M. 
Published: June 2024

Abstract
K-Ras inhibitor resistance in PDAC is associated with metabolic reprogramming towards a high OXPHOS state. Existing inhibitors of components of the electron transport chain have on-target toxicities that limit their use in the clinic, highlighting an opportunity to develop mechanistically orthogonal approaches. In this talk, I discuss our development of molecular glue degraders that target metabolic vulnerabilities in K-Ras inhibitor resistant PDAC.
Citation Format: Fleur M. Ferguson. Overcoming the K-Ras inhibitor resistant cell state in PDAC with molecular glues [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities; 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr IA002.
Abstract PR014: Combinatorial genetic screens to map synthetic lethal interactions and identify new cancer drug targets in KRAS mutant cancers
Authors: Arafeh Rand , Chang Laura , Sawyer Lydia , Wang Helen , McFarland James , Dempster Joshua , DeWeirdt Peter , Doench John , Hahn William C. 
Published: June 2024

Abstract
The success of precision oncology depends on our ability to translate accumulating genomic data into actionable treatment options in a personalized manner. The first step requires the identification of a specific genomic signature, then matching this signature with the most effective therapy. Unfortunately, more often than not, we do not have a specific cancer drug that is effective for the mutation found in a specific tumor. We desperately need to identify new targets so that we can develop new drugs to deliver on the promise of precision cancer medicine. In addition, we need to develop a rational way to combine drugs that does not depend on trial and error. Combinatorial genetic screening CRISPR-Cas9 now allows us to identify synthetic lethal interactions in which simultaneous perturbation of two genes leads to cell death. However, multiplex gene editing to reveal these synergies between genes is a major challenge. For model systems like yeast, high-throughput methods and technologies have made it possible to create genetic networks with around 23 million double mutants (6000 genes x 6000 genes) and has resulted in the most detailed genetic interaction network to date consisting of ∼900,000 genetic interactions. This landscape of genetic interaction network of yeast has taken the scientific research community 15 years. In human cells, there are ∼20,000 genes and 400 million combinations, making this very complex network impossible to screen and test all these 400M combinations. To systematically interrogate such genetic interactions, we designed a dual CRISPR-Cas9 perturbation library targeting the top 1000 genes upregulated in KRAS mutant cancers (lung, pancreas and colon cancers). We performed these combinatorial double knockout screens on 100K (100x1000) unique gene pairs and identified 27 pairs whose co-disruption results in a loss of cellular fitness. We next validated those top synthetic lethal pairs of genes by performing secondary screens using CRISPR-Cas12a on more KRAS mutant and KRAS WT cell lines. Overall, our findings will provide insight into potential combinational targets in KRAS mutant tumors and will highlight the synthetic lethality effects that occurs among the novel targets, and other proliferation, metastasis, immune and metabolism modules.
Citation Format: Rand Arafeh, Laura Chang, Lydia Sawyer, Helen Wang, James McFarland, Joshua Dempster, Peter DeWeirdt, John Doench, William C. Hahn. Combinatorial genetic screens to map synthetic lethal interactions and identify new cancer drug targets in KRAS mutant cancers [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities; 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr PR014.
Um caso de oligotimia na clínica psicopedagógica
Authors: Munimos Silvia Szterling 
Published: June 2024

Sob o império das neurociências, das terapias comportamentais e da medicalização na infância, a clínica dos distúrbios de aprendizagem inaugurada por Sara Pain está em desuso. A compreensão da função da ignorância na articulação do triângulo pai-mãe-filho e os significantes que a representam não encontram mais eco nos cursos de formação em psicopedagogia. O estudo de caso que aqui se apresenta, de um adolescente com problemas de aprendizagem e graves impasses na sua constituição subjetiva, pretende revisitar esse saber fazer psicopedagógico que media entre o conhecimento e o saber. Indiretamente, denuncia a falácia do discurso da inclusão escolar, que ao desconhecer a dimensão do inconsciente, dificulta ao educando assumir outra posição subjetiva que não a de “deficiente”.