bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pembrolizumab versus placebo as adjuvant therapy in stage IIB or IIC melanoma: Final analysis of distant metastasis-free survival in the phase 3 KEYNOTE-716 study.
Authors: Luke Jason J. , Ascierto Paolo Antonio , Khattak Muhammad Adnan , de la Cruz Merino Luis , Del Vecchio Michele , Rutkowski Piotr , Spagnolo Francesco , Mackiewicz Jacek , Chiarion-Sileni Vanna , Kirkwood John M. M. , Robert Caroline , Grob Jean-Jacques , de Galitiis Federica , Schadendorf Dirk , Carlino Matteo S. , Wu Larry , Fukunaga-Kalabis Mizuho , Krepler Clemens , Eggermont Alexander M. , Long Georgina V. 
Published: June 2023

LBA9505 Background: Adjuvant pembrolizumab significantly improved distant metastasis-free survival (DMFS) and recurrence-free survival (RFS) in patients with resected stage IIB or IIC melanoma versus placebo. We present the protocol-specified final DMFS analysis from KEYNOTE-716 (NCT03553836). Methods: Eligible patients were ≥12 years old with resected stage IIB or IIC cutaneous melanoma per American Joint Committee on Cancer, 8th edition, guidelines and a negative sentinel lymph node biopsy. In part 1 of the study, patients were randomly assigned (1:1) to pembrolizumab 200 mg (2 mg/kg up to 200 mg for pediatric patients) or placebo every 3 weeks for up to 17 cycles (~1 year) or until disease recurrence, unacceptable toxicity, or withdrawal. Randomization was stratified by T category for adults (T3b vs T4a vs T4b), with a separate stratum for pediatric patients. The primary end point was RFS per investigator review. DMFS per investigator review was a secondary end point. The protocol-specified final DMFS analysis was based on a target of 195 DMFS events. No formal hypothesis testing was performed because DMFS and RFS end points were met at previous interim analyses. The data cutoff date for this analysis was January 4, 2023. Results: Overall, 976 patients were randomly assigned to receive pembrolizumab (n = 487) or placebo (n = 489). Median duration of follow-up (time from randomization to the data cutoff date) was 39.4 months (range, 26.0-51.4). Compared with placebo, adjuvant pembrolizumab improved DMFS (medians: not reached; hazard ratio [HR], 0.59 [95% CI, 0.44-0.79]) and RFS (medians: not reached; HR, 0.62 [95% CI, 0.49-0.79]). The 36-month DMFS rate was 84.4% with adjuvant pembrolizumab versus 74.7% with placebo; the 36-month RFS rate was 76.2% with adjuvant pembrolizumab versus 63.4% with placebo. DMFS benefit with adjuvant pembrolizumab over placebo was observed regardless of cancer stage at baseline (stage IIB HR, 0.62 [95% CI, 0.42-0.92]; stage IIC HR, 0.57 [0.36-0.88]). Similar results were observed with RFS (stage IIB HR, 0.58 [95% CI, 0.43-0.79]; stage IIC HR, 0.65 [95% CI, 0.45-0.94]). No new safety signals were observed. Conclusions: With a median follow-up of 39.4 months, adjuvant pembrolizumab for resected stage IIB and IIC melanoma continued to show DMFS and RFS benefit over placebo, with no new safety signals. Clinical trial information: NCT03553836 .
Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: ASCO–College of American Pathologists Guideline Update
Authors: Wolff Antonio C. , Somerfield Mark R. , Dowsett Mitchell , Hammond M. Elizabeth H. , Hayes Daniel F. , McShane Lisa M. , Saphner Thomas J. , Spears Patricia A. , Allison Kimberly H. 
Published: June 2023

PURPOSE To update ASCO–College of American Pathologists (CAP) recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer. The Panel is aware that a new generation of antibody-drug conjugates (ADCs) targeting the HER2 protein is active against breast cancers that lack protein overexpression or gene amplification. METHODS An Update Panel conducted a systematic literature review to identify signals for updating recommendations. RESULTS The search identified 173 abstracts. Of five potential publications reviewed, none constituted a signal for revising existing recommendations. RECOMMENDATIONS The 2018 ASCO-CAP recommendations for HER2 testing are affirmed. DISCUSSION HER2 testing guidelines have focused on identifying HER2 protein overexpression or gene amplification in breast cancer to identify patients for therapies that disrupt HER2 signaling. This update acknowledges a new indication for trastuzumab deruxtecan when HER2 is not overexpressed or amplified but is immunohistochemistry (IHC) 1+ or 2+ without amplification by in situ hybridization. Clinical trial data on tumors that tested IHC 0 are limited (excluded from DESTINY-Breast04), and evidence is lacking that these cancers behave differently or do not respond similarly to newer HER2 ADCs. Although current data do not support a new IHC 0 versus 1+ prognostic or predictive threshold for response to trastuzumab deruxtecan, this threshold is now relevant because of the trial entry criteria that supported its new regulatory approval. Therefore, while it is premature to create new result categories of HER2 expression (eg, HER2-Low, HER2-Ultra-Low), best practices to distinguish IHC 0 from 1+ are now clinically relevant. This Update affirms prior HER2 reporting recommendations and offers a new HER2 testing reporting comment to highlight the current relevance of IHC 0 versus 1+ results and best practice recommendations to distinguish these often subtle differences. Additional information is available at www.asco.org/breast-cancer-guidelines .
Comprehensive Review on the Clinical Impact of Next-Generation Sequencing Tests for the Management of Advanced Cancer
Authors: Gibbs Sarah N. , Peneva Desi , Cuyun Carter Gebra , Palomares Melanie R. , Thakkar Snehal , Hall David W. , Dalglish Hannah , Campos Cynthia , Yermilov Irina 
Published: June 2023

PURPOSEThis review summarizes the published evidence on the clinical impact of using next-generation sequencing (NGS) tests to guide management of patients with cancer in the United States.METHODSWe performed a comprehensive literature review to identify recent English language publications that presented progression-free survival (PFS) and overall survival (OS) of patients with advanced cancer receiving NGS testing.RESULTSAmong 6,475 publications identified, 31 evaluated PFS and OS among subgroups of patients who received NGS-informed cancer management. PFS and OS were significantly longer among patients who were matched to targeted treatment in 11 and 16 publications across tumor types, respectively.CONCLUSIONOur review indicates that NGS-informed treatment can have an impact on survival across tumor types.
DeXtrusion: automatic recognition of epithelial cell extrusion through machine learning in vivo
Authors: Villars Alexis , Letort Gaëlle , Valon Léo , Levayer Romain 
Published: June 2023

ABSTRACT
Accurately counting and localising cellular events from movies is an important bottleneck of high-content tissue/embryo live imaging. Here, we propose a new methodology based on deep learning that allows automatic detection of cellular events and their precise xyt localisation on live fluorescent imaging movies without segmentation. We focused on the detection of cell extrusion, the expulsion of dying cells from the epithelial layer, and devised DeXtrusion: a pipeline based on recurrent neural networks for automatic detection of cell extrusion/cell death events in large movies of epithelia marked with cell contour. The pipeline, initially trained on movies of the Drosophila pupal notum marked with fluorescent E-cadherin, is easily trainable, provides fast and accurate extrusion predictions in a large range of imaging conditions, and can also detect other cellular events, such as cell division or cell differentiation. It also performs well on other epithelial tissues with reasonable re-training. Our methodology could easily be applied for other cellular events detected by live fluorescent microscopy and could help to democratise the use of deep learning for automatic event detections in developing tissues.
Analysis of the function of ADAM17 in iRhom2 curly-bare and tylosis with esophageal cancer mutant mice
Authors: Rabinowitsch Ariana I. , Maretzky Thorsten , Weskamp Gisela , Haxaire Coline , Tueshaus Johanna , Lichtenthaler Stefan F. , Monette Sébastien , Blobel Carl P. 
Published: June 2023

ABSTRACT
Tylosis with oesophageal cancer (TOC) is a rare familial disorder caused by cytoplasmic mutations in inactive rhomboid 2 (iRhom2 or iR2, encoded by Rhbdf2). iR2 and the related iRhom1 (or iR1, encoded by Rhbdf1) are key regulators of the membrane-anchored metalloprotease ADAM17, which is required for activating EGFR ligands and for releasing pro-inflammatory cytokines such as TNFα (or TNF). A cytoplasmic deletion in iR2, including the TOC site, leads to curly coat or bare skin (cub) in mice, whereas a knock-in TOC mutation (toc) causes less severe alopecia and wavy fur. The abnormal skin and hair phenotypes of iR2cub/cub and iR2toc/toc mice depend on amphiregulin (Areg) and Adam17, as loss of one allele of either gene rescues the fur phenotypes. Remarkably, we found that iR1−/− iR2cub/cub mice survived, despite a lack of mature ADAM17, whereas iR2cub/cub Adam17−/− mice died perinatally, suggesting that the iR2cub gain-of-function mutation requires the presence of ADAM17, but not its catalytic activity. The iR2toc mutation did not substantially reduce the levels of mature ADAM17, but instead affected its function in a substrate-selective manner. Our findings provide new insights into the role of the cytoplasmic domain of iR2 in vivo, with implications for the treatment of TOC patients.
INFRAESTRUTURA DE TRANSPORTE, DESENVOLVIMENTO SOCIOECONÔMICO E MEIO AMBIENTE
Authors: Rocha Fernando , Caixeta Filho José Vicente 
Published: June 2023

Os investimentos em infraestruturas de transporte são frequentemente associados ao desenvolvimento socioeconômicos dos países. A relação existente entre o desenvolvimento econômico a partir da presença das infraestruturas de transporte, bem como os impactos ambientais a elas associadas, são temáticas de interesse da literatura acadêmica. Esse é o objeto de análise desse artigo, que, a partir do uso de técnicas bibliométricas, discorre sobre como a literatura acadêmica tem abordado essas questões. Em suma, diversos são os trabalhos fazem análises das infraestruturas de transporte sob um conjunto de variáveis ambientais, econômicas e sociais. Dentre as temáticas emergentes, a que trata das relações entre infraestrutura de transporte e a elaboração de políticas públicas baseadas em aspectos mais abrangentes de análise é objeto de pesquisa relevante.
Stateful Posted Pricing with Vanishing Regret via Dynamic Deterministic Markov Decision Processes
Authors: Emek Yuval , Lavi Ron , Niazadeh Rad , Shi Yangguang 
Published: June 2023

An online problem called dynamic resource allocation with capacity constraints (DRACC) is introduced and studied in the realm of posted price mechanisms. This problem subsumes several applications of stateful pricing, including but not limited to posted prices for online job scheduling and matching over a dynamic bipartite graph. Because existing online learning techniques do not yield vanishing regret for this problem, we develop a novel online learning framework over deterministic Markov decision processes with dynamic state transition and reward functions. Following that, we prove, based on a reduction to the well-studied problem of online learning with switching costs, that if the Markov decision process admits a chasing oracle (i.e., an oracle that simulates any given policy from any initial state with bounded loss), then the online learning problem can be solved with vanishing regret. Our results for the DRACC problem and its applications are then obtained by devising (randomized and deterministic) chasing oracles that exploit the particular structure of these problems. Funding: The work of Y. Emek was supported in part by the Israel Science Foundation [Grant 1016/17]. The work of R. Lavi was partially supported by the Israel Science Foundation [Grant 2560/17] and the National Natural Science Foundation of China [Grant 2560/17]. The work of R. Niazadeh was supported by the University of Chicago Booth School of Business. The work of Y. Shi was partially supported at the Technion by the Council for Higher Education [fellowship], and at Shandong University by the Science Fund Program of Shandong Province for Distinguished Oversea Young Scholars [Grant 2023HWYQ-006].
Assortment Optimization Under the Multi-Purchase Multinomial Logit Choice Model
Authors: Bai Yicheng , Feldman Jacob , Segev Danny , Topaloglu Huseyin , Wagner Laura 
Published: June 2023

Updating a Classic: Assortment Optimization under the Multi-Purchase MNL Model In the paper “Updating a Classic: Assortment Optimization under the Multi-Purchase MNL Model,” our primary contribution resides in proposing the first multi-purchase choice model that can be fully operationalized. Our main algorithmic results consist of two distinct polynomial time approximation schemes (PTAS); the first, and simpler of the two, caters to a setting where each customer may buy only a constant number of products, whereas the second, more nuanced algorithm applies to our multi-purchase model in its general form. Additionally, we study the revenue potential of making assortment decisions that account for multi-purchase behavior in comparison with those that overlook this phenomenon. In particular, we relate both the structure and revenue performance of the optimal assortment under a traditional single-purchase model to that of the optimal assortment in the multi-purchase setting.
“We really are seeing racism in the hospitals”: Racial identity, racism, and doula care for diverse populations in Georgia
Authors: Sayyad Ayeesha , Lindsey Alyssa , Narasimhan Subasri , Turner Daria , Shah Priya , Lindberg Ky , Mosley Elizabeth A. 
Published: June 2023

Introduction
Poor birth outcomes are more prevalent for Black communities, but strong evidence shows that doula care can improve those outcomes. More evidence is needed to understand racial differences, discrimination, and equity in doula care.

Methods
The current study’s objective was to describe the experiences of Black doulas as well as the challenges and facilitators of providing doula care to communities of color in Georgia. From Fall 2020-Fall 2021, 20 surveys and in-depth interviews were conducted with doulas as part of a community-based participatory study co-led by Healthy Mothers, Healthy Babies Coalition of Georgia and academic researchers.

Results
Doula participants were diverse in age (5% under 25, 40% 25–35, 35% 36–45, and 20% 46+) and race/ethnicity (45% white, 50% Black, 5% Latinx). Most (70%) Black doulas reported that more than 75% of their clientele is Black, while most (78%) white doulas reported that less than 25% of their clientele is Black. Doulas noted the alarming Black maternal mortality rate and how mistreatment causes Black clients to lose trust in medical staff, leaving them in need of advocates. Black doulas were passionate about serving and advocating with Black clients. Participants also described how language and cultural barriers, particularly for Asian and Latinx people, reduce clients’ ability to self-advocate, increasing the need for doulas. Doulas also discussed the ways that race influences their connections with clients and their dissatisfaction with the lack of cultural humility or sensitivity training in standard doula training.

Conclusion
Our findings indicate that Black doulas provide essential and supportive services to Black birthing people, and those services are more urgently needed than ever following the overturn of Roe v. Wade. Doula training must be improved to address the cultural needs of diverse clients. Increasing access to doula care for Asian and Latinx communities could also address language and cultural barriers that can negatively impact their maternal and child health outcomes.
Physiological mechanisms of muscle strength and power are dependent on the years post obtaining peak height velocity in elite juniors rowers: A cross-sectional study
Authors: Almeida-Neto Paulo Francisco de , de Morais Ferreira Ayrton Bruno , Baxter-Jones Adam , de Medeiros Jason Azevedo , Felipe da Silva Luiz , Silva Dantas Paulo Moreira , Cabral Breno Guilherme de Araújo Tinôco 
Published: June 2023

BackgroundIt is not yet known whether the years after peak height velocity (PHV) are associated with the physiological mechanisms of muscle strength and power in Juniors rowers.ObjectiveTo identify the association between years post PHV (YPPHV) with muscle power and strength in Juniors rowers.MethodsWe tested 235 Brazilian rowing athletes (male: 171, female: 64, Juniors category). We measured: power (indoor rowing over 100-m, 500-m, 2,000-m and 6,000-m) and muscle strength (one repetition maximum (1RM) test in squat, deadlift, bench press and bent row on the bench). Biological maturation was index by age of PHV. The sample was divided into groups considering YPPHV recent (2.5 to 3.9), median (2.51 to 4.9) and veteran (>4.9). We use a Baysian approach to data handling.ResultsWhen compared to their peers in the recent and median post PHV groups, the male veteran group were superior in muscle power (Absolute: 100-m (BF10: 2893.85), 500-m (BF10: 553.77) and 6,000-m (BF10: 22.31). Relative: (100-m (BF10: 49.9)) and strength (BF10≥10.0 in squat, bench press and deadlift), and in the female the veteran group were superior in test time (500-m, BF10: 88.4).ConclusionIn elite Juniors rowers the increasing YPPHV are associated with muscle power performance in both sexes and muscle strength performance in males.
Recurrence of Brunner Gland Adenocarcinoma After Duodenectomy and Gastrojejunostomy
Authors: Hong Paul , Ghanim Marcel , Haseeb Abdul , Ding Xianzhong , Abegunde Ayokunle T. 
Published: June 2023

ABSTRACT
Malignant neoplasms arising from the Brunner gland are exceedingly rare. A 62-year-old man with a history of surgical resection of Brunner gland adenocarcinoma presented with upper extremity cellulitis. Hospital course was complicated by atrial fibrillation and hematochezia. Bidirectional endoscopy was negative; however, small bowel enteroscopy revealed recurrence of Brunner gland adenocarcinoma 6 years after surgical resection. To our knowledge, this is the first reported case of recurrent Brunner gland adenocarcinoma after curative resection.
Hepatocellular Carcinoma Recurrence as Isolated Adrenal Metastasis
Authors: Zeineddine Fadl A. , Ahmed Zunirah , Victor David , Farach Andrew , Divatia Mukul , Kodali Sudha 
Published: June 2023

ABSTRACT
Hepatocellular carcinoma is the sixth most common cancer in the Western world. The most frequent sites of metastasis are lungs, lymph nodes, and bones. Risk factors for extrahepatic metastasis are advanced intrahepatic lesions, vascular invasion, elevated tumor markers, and viral hepatitis. Isolated metachronous adrenal metastasis occurring after liver transplantation is exceedingly rare.
Strategi Penataan Ruang Publik Pada Kota Lama Di Semarang Berdasarkan Public Space Index Pada Masa Pandemi COVID-19
Authors: Panjaitan Helga Ezra Novita , Wungo Grandy Loranessa 
Published: June 2023

Urban spatial planning cannot be separated from the element of public open space. During the COVID-19 pandemic, public space are also used as alternative tourism munity as well as a place to unwind, so that must be balanced with good quality as well. In this study, researchers took the road corridor Letjen Soeprapto which is one of the public spaces in the Kota Lama which has quite a number of building arrangements including high priority buildings, however durig the COVID-19 pandemic this route still uses normal standards before the pandemic and did not have a design that was responsive to the pandemic so that it experionced a drastic decrease in visitors. The purpose of this study is to develop a strategy for structuring the public space of Kota Lama based on the Public Space Index during the COVID-19 pandemic. The quality measurement is based on the Public Space Index (PSI) which is based on the observations of researchers and perceptions of visitors. The analysis used is Behavior Mapping, Simpson's Diversity Index, Public Space Index, and SWOT analysis. The results of the Public Space Index as a whole, the quality of public space in the Old City is quite good with a total value of 108.39 PSI from a maximum value of 150, so that the structuring strategy obtained from the SWOT analysis shows that in general the arrangement that can be done is the addition of responsive facilities during the COVID- 19 pandemic.
Peran Mayarakat dalam Eksistensi Kampung Kota (Studi Kasus: Kampung Pelangi Kota Semarang)
Authors: Fitriani Fitriani , Wijaya Holi Bina 
Published: June 2023

Kampung Wonosari merupakan salah satu kampung yang dalam sejarahnya diperuntukkan sebagai kawasan pemakaman. Namun, lokasi Kampung Wonosari yang berada di pusat kota yang dekat dengan pusat pemerintahan, Tugu Muda, Lawang Sewu, sarana kesehatan RSUD Kariadi, serta pusat perniagaan pandanaran, menyebabkan berubahnya peruntukan Kampung Wonosari. Lambat laun Kampung Wonosari berubah dari dominasi lahan pemakaman kini didominasi menjadi lahan permukiman yang tidak tertata. Ekistensi kampung kota sebagai tempat bermukim yang berkualitas bagi masyarakat perkotaan dapat dilakukan melalui penggalian potensi dari berbagai sektor, tentu saja hal ini tidak lepas kaitannya dengan peran masyarakat didalamnya. Tujuan penelitian ini adalah untuk melihat peran masyarakat dalam eksistensi Kampung Pelangi di Kota Semarang. Hasil dari penelitian menunjukkan bahwa pada analisis eksistensi Kampung Pelangi sebagai kampung kota tergolong dalam kriteria kuat. Hal ini dikarenakan Kampung Pelangi dapat memberikan identitas pada suatu kota dimana masih terlihat wajah asli kampung yaitu ditandai dengan adanya makam bersejarah yang masih dilestarikan serta ikatan-ikatan sosial dan adat istiadat yang masih terjalin dalam masyarakat Kampung Pelangi. Kondisi ini tentunya berpengaruh berhadap peran masyarakat yang sudah berkontribusi tinggi terlibat dalam pelaksanaan aktivitas dan pembangunan di Kampung Pelangi. Dalam program pembentukan Kampung Pelangi masyarakat tidak ikut terlibat dalam inisiasi pembentukan Kampung Pelangi, pemerintahlah yang berperan penting mulai dari inisiasi, implementasi, dan monitoring. Masyarakat hanya terlibat dalam pelaksanaan aktivitas pembangunan saja, sehingga inisiatif masyarakat masih hanya terbatas arahan pemerintah saja. Kondisi ini juga terkait dengan keberadaan organisasi lokal (pokdarwis) di Kampung Pelangi dimana peran pokdarwis untuk pengembangan Kampung Pelangi hanya jika ada arahan dari kelurahan saja atau pemerintah kota semarang dalam mewujudkan Kampung Pelangi menjadi destinasi yang menarik untuk dikunjungi yang memang pada dasarnya sudah menjadi program pemkot Semarang. Meskipun begitu keberadaan pokdarwis cukup bermanfaat bagi masyarakat Kampung Pelangi yang berperan dalam pengadaan event-event kegiatan wisata. Sedangkan untuk penilaian kapasitas masyarakat sendiri berada pada kategori sedang. Kegiatan pengembangan kapasitas masyarakat di Kampung Pelangi belum sepenuhnya berhasil mengatasi permasalahan Kampung Pelangi karena belum adanya monitoring secara berkelanjutan terkait program kegiatan dalam peningkatan kapasitas masyarakat.