bluuebunny/crossref_metadata_2025_split huggingface dataset:
RAS/RAF Comutation and ERBB2 Copy Number Modulates HER2 Heterogeneity and Responsiveness to HER2-directed Therapy in Colorectal Cancer
Authors: Singh Harshabad , Sahgal Pranshu , Kapner Kevin , Corsello Steven M. , Gupta Hersh , Gujrathi Rahul , Li Yvonne Y. , Cherniack Andrew D. , El Alam Raquelle , Kerfoot Joseph , Andrews Elizabeth , Lee Annette , Nambiar Chetan , Hannigan Alison M. , Remland Joshua , Brais Lauren , Leahy Meghan E. , Rubinson Douglas A. , Schlechter Benjamin L. , Meyerson Matthew , Kuang Yanan , Paweletz Cloud P. , Lee Jessica K. , Quintanilha Julia C.F. , Aguirre Andrew J. , Perez Kimberly J. , Huffman Brandon M. , Rossi Humberto , Abrams Thomas A. , Kabraji Sheheryar , Trusolino Livio , Bertotti Andrea , Sicinska Ewa T. , Parikh Aparna R. , Wolpin Brian M. , Schrock Alexa B. , Giannakis Marios , Ng Kimmie , Meyerhardt Jeffrey A. , Hornick Jason L. , Sethi Nilay S. , Cleary James M. 
Published: February 2024

Abstract

Purpose:
ERBB2-amplified colorectal cancer is a distinct molecular subtype with expanding treatments. Implications of concurrent oncogenic RAS/RAF alterations are not known.

Experimental Design:
Dana-Farber and Foundation Medicine Inc. Colorectal cancer cohorts with genomic profiling were used to identify ERBB2-amplified cases [Dana-Farber, n = 47/2,729 (1.7%); FMI, n = 1857/49,839 (3.7%)]. Outcomes of patients receiving HER2-directed therapies are reported (Dana-Farber, n = 9; Flatiron Health-Foundation Medicine clinicogenomic database, FH-FMI CGDB, n = 38). Multisite HER2 IHC and genomic profiling were performed to understand HER2 intratumoral and interlesional heterogeneity. The impact of concurrent RAS comutations on the effectiveness of HER2-directed therapies were studied in isogenic colorectal cancer cell lines and xenografts.

Results:
ERBB2 amplifications are enriched in left-sided colorectal cancer. Twenty percent of ERBB2-amplified colorectal cancers have co-occurring oncogenic RAS/RAF alterations. While RAS/RAF WT colorectal cancers typically have clonal ERBB2 amplification, colorectal cancers with co-occurring RAS/RAF alterations have lower level ERRB2 amplification, higher intratumoral heterogeneity, and interlesional ERBB2 discordance. These distinct genomic patterns lead to differential responsiveness and patterns of resistance to HER2-directed therapy. ERBB2-amplified colorectal cancer with RAS/RAF alterations are resistant to trastuzumab-based combinations, such as trastuzumab/tucatinib, but retain sensitivity to trastuzumab deruxtecan in in vitro and murine models. Trastuzumab deruxtecan shows clinical efficacy in cases with high-level ERBB2-amplified RAS/RAF coaltered colorectal cancer.

Conclusions:
Co-occurring RAS/RAF alterations define a unique subtype of ERBB2-amplified colorectal cancer that has increased intratumoral heterogeneity, interlesional discordance, and resistance to trastuzumab-based combinations. Further examination of trastuzumab deruxtecan in this previously understudied cohort of ERBB2-amplified colorectal cancer is warranted.
Low-dose Paclitaxel with Pembrolizumab Enhances Clinical and Immunologic Responses in Platinum-refractory Urothelial Carcinoma
Authors: Bitting Rhonda L. , Tooze Janet A. , Goodman Michael , Vile Donald C. , Brown Jessica M. , Thomas Christopher Y. , Neve Morgan , Kooshki Mitra , Addo Safoa , Triozzi Pierre L. , Dubey Purnima 
Published: February 2024

Abstract

Purpose:
Single-agent checkpoint inhibition is effective in a minority of patients with platinum-refractory urothelial carcinoma; therefore, the efficacy of combining low-dose paclitaxel with pembrolizumab was tested.

Materials and Methods:
This was a prospective, single-arm phase II trial with key inclusion criteria of imaging progression within 12 months of platinum therapy and Eastern Cooperative Oncology Group ≤1. Treatment was pembrolizumab 200 mg day 1 and paclitaxel 80 mg/m2 days 1 and 8 of a 21-day cycle for up to eight cycles unless progression or unacceptable adverse events (AE). The primary endpoint was overall response rate (ORR) with overall survival (OS), 6-month progression-free survival (PFS), and safety as key secondary endpoints. Change in circulating immune cell populations, plasma, and urinary miRs were evaluated.

Results:
Twenty-seven patients were treated between April 2016 and June 2020, with median follow-up of 12.4 months. Baseline median age was 68 years, with 81% men and 78% non-Hispanic White. ORR was 33% by intention to treat and 36% in imaging-evaluable patients with three complete responses. Six-month PFS rate was 48.1% [95% confidence interval (CI): 28.7–65.2] and median OS 12.4 months (95% CI: 8.7 months to not reached). Common ≥ grade 2 possibly-related AEs were anemia, lymphopenia, hyperglycemia, and fatigue; grade 3/4 AEs occurred in 56%, including two immune-mediated AEs (pneumonitis and nephritis). Responding patients had a higher percentage of circulating CD4+IFNγ+ T cells. Levels of some miRs, including plasma miR 181 and miR 223, varied in responders compared with nonresponders.

Conclusions:
The addition of low-dose paclitaxel to pembrolizumab is active and safe in platinum-refractory urothelial carcinoma.

Significance:
We found that combining pembrolizumab with low-dose paclitaxel may be effective in patients with urothelial carcinoma progressing on platinum chemotherapy, with favorable safety profiles.
Contribuições para a análise da educação básica brasileira durante a ditadura civil militar: resultados preliminares
Authors: Vidal Bia Paixão , Vieira Isabel Nogueira 
Published: February 2024

O presente artigo integra os estudos realizados no projeto de pesquisa intitulado “A Educação Brasileira de 1964 a 1985: impactos da ditadura” e apresenta alguns dos resultados preliminares do mesmo. Neste texto apresentamos um panorama das questões relacionadas à educação básica brasileira no primeiro momento da ditadura, governo Castello Branco relacionando com o olhar das informações do periódico Última Hora, considerado o periódico de oposição de maior circulação, no último dia de governo João Goulart. Estamos, por esse caminho, iniciando uma discussão que traga à tona elementos capazes de permitir reflexões acerca das formas estratégicas do sistema educacional brasileiro na atualidade.
Long-Term Outcomes of Cardiac Resynchronization Therapy in Patients With Repaired Tetralogy of Fallot: A Multicenter Study
Authors: Ramdat Misier Nawin L. , Moore Jeremy P. , Nguyen Hoang H. , Lloyd Michael S. , Dubin Anne M. , Mah Douglas Y. , Czosek Richard J. , Khairy Paul , Chang Philip M. , Nielsen Jens C. , Aydin Alper , Pilcher Thomas A. , O’Leary Edward T. , Shivkumar Kalyanam , de Groot Natasja M.S. 
Published: February 2024

BACKGROUND:
A growing number of patients with tetralogy of Fallot develop left ventricular systolic dysfunction and heart failure, in addition to right ventricular dysfunction. Although cardiac resynchronization therapy (CRT) is an established treatment option, the effect of CRT in this population is still not well defined. This study aimed to investigate the early and late efficacy, survival, and safety of CRT in patients with tetralogy of Fallot.

METHODS:
Data were analyzed from an observational, retrospective, multicenter cohort, initiated jointly by the Pediatric and Congenital Electrophysiology Society and the International Society of Adult Congenital Heart Disease. Twelve centers contributed baseline and longitudinal data, including vital status, left ventricular ejection fraction (LVEF), QRS duration, and NYHA functional class. Outcomes were analyzed at early (3 months), intermediate (1 year), and late follow-up (≥2 years) after CRT implantation.

RESULTS:

A total of 44 patients (40.3±19.2 years) with tetralogy of Fallot and CRT were enrolled. Twenty-nine (65.9%) patients had right ventricular pacing before CRT upgrade. The left ventricular ejection fraction improved from 32% [24%–44%] at baseline to 42% [32%–50%] at early follow-up (
P
<0.001) and remained improved from baseline thereafter (
P
≤0.002). The QRS duration decreased from 180 [160–205] ms at baseline to 152 [133–182] ms at early follow-up (
P
<0.001) and remained decreased at intermediate and late follow-up (
P
≤0.001). Patients with upgraded CRT had consistent improvement in left ventricular ejection fraction and QRS duration at each time point (
P
≤0.004). Patients had a significantly improved New York Heart Association functional class after CRT implantation at each time point compared with baseline (
P
≤0.002). The transplant-free survival rates at 3, 5, and 8 years after CRT implantation were 85%, 79%, and 73%.

CONCLUSIONS:
In patients with tetralogy of Fallot treated with CRT consistent improvement in QRS duration, left ventricular ejection fraction, New York Heart Association functional class, and reasonable long-term survival were observed. The findings from this multicenter study support the consideration of CRT in this unique population.
Texts, Bodies, Images, Movement
Authors: Alonso Fernández Zoa 
Published: February 2024

Abstract
The international symposium Imprints of Ancient Greek and Roman Dance: Texts, Bodies, Images, Movement took place in Madrid in September 2022. As the final component of a research project funded by the Spanish Society of Classical Studies and the BBVA Foundation, this event aimed to scrutinize a series of concepts that have proven significant to the transhistorical and transcultural study of dance. The eight scholars tasked with examining these concepts presented interesting case studies of ancient Greek and Roman dancing between the Archaic period and late Antiquity, drawing upon a variety of media and sources.
Proposed New Article on the Date and Authorship of Names Originally Published with Incomplete Protologues
Authors: De Queiroz Kevin , Cantino Philip , Cellinese Nico 
Published: February 2024

When authors have proposed phylogenetically defined names that satisfy the requirements for publication but not those for establishment, the protologues must either be corrected with published errata or republished in a way that satisfies the requirements. The current version of the PhyloCode does not indicate whether the authorship and date of the names are those of the original publication in which the names were proposed or those of the subsequently published errata or full protologues in which all the requirements for establishment were satisfied. We propose modifications to the PhyloCode such that for converted clade names (Art. 6.3), the nominal author(s) (Art. 19.1) and date are those of the original publication in which the name was proposed (not the one in which it was first defined phylogenetically), but the definitional author(s) (Art. 19.1) and date are those of the subsequent publication in which all the requirements for establishment are satisfied. For new clade names (Art. 9.1), we propose that both the nominal author(s) and date and the definitional author(s) and date are those of the subsequent publication in which all the requirements for establishment are satisfied. An exception is proposed for new clade names that are simultaneously established under a rank-based code.
Attachment styles and associated psychosocial factors in patients at ultra-high risk for psychosis: A systematic review
Authors: Barbeito Sara , Gómez-Juncal Rocío , Vega Patricia , Antonio Becerra Juan , Petkari Eleni , González-Pinto Ana , Sánchez-Gutiérrez Teresa 
Published: February 2024

Background: Patients with an ultra-high risk of psychosis (UHR) are more likely to transition to psychosis. Attachment style has also been associated with psychosis and other symptoms. Aims: To review attachment styles in UHR patients and to analyze related psychosocial factors. Ours is the first systematic review of attachment in this population. Method: We performed a systematic review of attachment and related psychosocial factors in UHR patients following the PRISMA methodology. Results: We identified five studies. The results revealed high rates of insecure attachment in this population (more than 80%). The UHR sample presented high levels of depression, anxiety, social anxiety, emotional reactivity, trauma, and poor mentalization. Premorbid social adjustment was a predictor of improvement in disorganization and negative symptoms. The rate of transition to psychosis was 10%. Attachment patterns accounted for 16.8% of the variance. This vulnerability for psychosis was also associated with poor mentalization. Conclusion: Early detection of patients with UHR and insecure attachment is crucial, since early intervention to address symptoms, mentalization, and attachment is feasible and may lead to an improvement in the remaining associated psychosocial related factors (secure style: better global functioning and less affective and anxious symptoms). PROSPERO ID440957
Evaluation of Smile Characteristics of Attractive Smile in Various Growth Patterns
Authors: Senthilkumar Akiladevi , Krishnan Prabhakar , Arasappan Raja , Muthukumar Karthi , Subramani Raja , Parvin Rehna 
Published: February 2024

Objective To investigate the dynamic aspect of attractive smile and smile parameters in different growth patterns. Methods Participants ranging in age from 17 to 25 years were randomly selected and videographic records of smile were obtained. A panel of two orthodontists, two prosthodontists, and two laypersons were involved in the selection of attractive smile. Inter-examiner variability was also assessed. The final sample of 84 participants with attractive smile were grouped into three categories based on clinical FMA into average, horizontal, and vertical growth pattern. Upper lip length = ULL-R, Lower lip length = LLL-R were measured on rest photographs. Upper lip length = ULL-S, Lower lip length = LLL-S, Upper lip thickness = ULT, Lower lip thickness = LLT, Maxillary incisal display = MID, Interlabial gap = ILG, Outer inter commissural width = ICW, Buccal corridor space = BC were measured on smile photographs. Pearson’s Chi-square test was done for the perception of attractiveness of smile. Differences among the three groups was subjected to one-way analysis of variance and Tukey’s post hoc test. Results Highly significant correlation was observed among orthodontists, prosthodontists, and laypersons in assessing attractiveness of smile. Vertical parameters such as upper lip length at rest, upper lip length during smile, lower lip length at rest, lower lip length during smile, and lower lip thickness (LLT) were significantly increased in the vertical pattern when compared with the average and horizontal growth pattern, whereas buccal corridor space was the least in horizontal growth pattern. Conclusion Growth patterns appear to have an influence on perception of smile esthetics and smile parameters. This suggests that care should be taken while framing treatment goals considering the significant differences among growth patterns. Strong correlation was observed among orthodontists, prosthodontists, and laypersons in assessing attractiveness of smile. ULL-R, ULL-S, LLL-R, LLL-S, and ΔULL show a significantly higher value in vertical growth pattern when compared to average and horizontal growth pattern. The buccal corridor space (BC) among the participants was the least in horizontal growth pattern.
From Humanitarian Intervention to Regime Change in Libya: Human Agency in the Production and Transformation of Global Security Assemblages
Authors: Robson Matthew 
Published: February 2024

The paper examines human agency in the production and transformation of global security assemblages. A situated conception of human agency is elaborated theoretically through the reincorporation of key concepts from Gilles Deleuze and Felix Guattari’s original oeuvre, such as ‘bodies’ ‘desire’ and ‘affect’. Through this Deleuzoguattarian assemblage framework it becomes possible to distinguish between human/non-human and active/reactive forms of agency, while not losing sight of how human actions invariably take place within broader structures of signification. To showcase the utility and analytical potential of this approach, the paper returns to a paradigmatic case of global security cooperation in recent times: the military intervention in Libya of 2011. Through the assemblage framework advocated it is illustrated how the agency of the governments of the United Kingdom, France and the United States is crucial for making connections with other bodies in the production of a Libyan humanitarian intervention assemblage, and later bringing about its transformation into a Libyan regime change assemblage. More than this, it becomes possible to grasp how in fact both these processes form part of a single Western-led biopolitical-geopolitical strategy. The paper concludes by emphasising the political and ethical significance of an appreciation of human agency in global security assemblages. De l’intervention humanitaire au renversement du régime en Libye : l’agentivité humaine dans la production et la transformation des agencements de la sécurité mondiale
Unsupervised Machine Learning of the Combined Danish and Norwegian Knee Ligament Registers: Identification of 5 Distinct Patient Groups With Differing ACL Revision Rates
Authors: Martin R. Kyle , Wastvedt Solvejg , Pareek Ayoosh , Persson Andreas , Visnes Håvard , Fenstad Anne Marie , Moatshe Gilbert , Wolfson Julian , Lind Martin , Engebretsen Lars 
Published: February 2024

Background: Most clinical machine learning applications use a supervised learning approach using labeled variables. In contrast, unsupervised learning enables pattern detection without a prespecified outcome. Purpose/Hypothesis: The purpose of this study was to apply unsupervised learning to the combined Danish and Norwegian knee ligament register (KLR) with the goal of detecting distinct subgroups. It was hypothesized that resulting groups would have differing rates of subsequent anterior cruciate ligament reconstruction (ACLR) revision. Study Design: Cohort study; Level of evidence, 3. Methods: K-prototypes clustering was performed on the complete case KLR data. After performing the unsupervised learning analysis, the authors defined clinically relevant characteristics of each cluster using variable summaries, surgeons’ domain knowledge, and Shapley Additive exPlanations analysis. Results: Five clusters were identified. Cluster 1 (revision rate, 9.9%) patients were young (mean age, 22 years; SD, 6 years), received hamstring tendon (HT) autograft (91%), and had lower baseline Knee injury and Osteoarthritis Outcome Score (KOOS) Sport and Recreation (Sports) scores (mean, 25.0; SD, 15.6). Cluster 2 (revision rate, 6.9%) patients received HT autograft (89%) and had higher baseline KOOS Sports scores (mean, 67.2; SD, 16.5). Cluster 3 (revision rate, 4.7%) patients received bone–patellar tendon–bone (BPTB) or quadriceps tendon (QT) autograft (94%) and had higher baseline KOOS Sports scores (mean, 65.8; SD, 16.4). Cluster 4 (revision rate, 4.1%) patients received BPTB or QT autograft (88%) and had low baseline KOOS Sports scores (mean, 20.5; SD, 14.0). Cluster 5 (revision rate, 3.1%) patients were older (mean age, 42 years; SD, 7 years), received HT autograft (89%), and had low baseline KOOS Sports scores (mean, 23.4; SD, 17.6). Conclusion: Unsupervised learning identified 5 distinct KLR patient subgroups and each grouping was associated with a unique ACLR revision rate. Patients can be approximately classified into 1 of the 5 clusters based on only 3 variables: age, graft choice (HT, BPTB, or QT autograft), and preoperative KOOS Sports subscale score. If externally validated, the resulting groupings may enable quick risk stratification for future patients undergoing ACLR in the clinical setting. Patients in cluster 1 are considered high risk (9.9%), cluster 2 patients medium risk (6.9%), and patients in clusters 3 to 5 low risk (3.1%-4.7%) for revision ACLR.
The Mental Health of First Nations Children in Manitoba: A Population-Based Retrospective Cohort Study Using Linked Administrative Data: La santé mentale des enfants des Premières Nations au Manitoba : une étude de cohorte rétrospective dans la population, à l’aide de données administratives liées
Authors: Chartier Mariette J , Brownell Marni , Star Leona , Murdock Nora , Campbell Rhonda , Phillips-Beck Wanda , Horton Mabel , Meade Chelsey , Au Wendy , Schultz Jennifer , Bowes John-Michael , Cochrane Brooke 
Published: February 2024

Objective First Nations children face a greater risk of experiencing mental disorders than other children from the general population because of family and societal factors, yet there is little research examining their mental health. This study compares diagnosed mental disorders and suicidal behaviours of First Nations children living on-reserve and off-reserve to all other children living in Manitoba. Method The research team, which included First Nations and non-First Nations researchers, utilized population-based administrative data that linked de-identified individual-level records from the 2016 First Nations Research File to health and social information for children living in Manitoba. Adjusted rates and rate ratios of mental disorders and suicide behaviours were calculated using a generalized linear modelling approach to compare First Nations children ( n = 40,574) and all other children ( n = 197,109) and comparing First Nations children living on- and off-reserve. Results Compared with all other children, First Nations children had a higher prevalence of schizophrenia (adjusted rate ratio (aRR): 4.42, 95% confidence interval (CI), 3.36 to 5.82), attention-deficit hyperactivity disorder (ADHD; aRR: 1.21, 95% CI, 1.09 to 1.33), substance use disorders (aRR: 5.19; 95% CI, 4.25 to 6.33), hospitalizations for suicide attempts (aRR: 6.96; 95% CI, 4.36 to 11.13) and suicide deaths (aRR: 10.63; 95% CI, 7.08 to 15.95). The prevalence of ADHD and mood/anxiety disorders was significantly higher for First Nations children living off-reserve compared with on-reserve; in contrast, hospitalization rates for suicide attempts were twice as high on-reserve than off-reserve. When the comparison cohort was restricted to only other children in low-income areas, a higher prevalence of almost all disorders remained for First Nations children. Conclusion Large disparities were found in mental health indicators between First Nations children and other children in Manitoba, demonstrating that considerable work is required to improve the mental well-being of First Nations children. Equitable access to culturally safe services is urgently needed and these services should be self-determined, planned, and implemented by First Nations people.