bluuebunny/crossref_metadata_2025_split huggingface dataset:
Streamlining the Generation of Advanced Polymer Materials Through the Marriage of Automation and Multiblock Copolymer Synthesis in Emulsion
Authors: Clothier Glenn K. K. , Guimarães Thiago R. , Thompson Steven W. , Howard Shaun C. , Muir Benjamin W. , Moad Graeme , Zetterlund Per B. 
Published: February 2024

AbstractSynthetic polymers are of paramount importance in modern life ‐ an incredibly wide range of polymeric materials possessing an impressive variety of properties have been developed to date. The recent emergence of artificial intelligence and automation presents a great opportunity to significantly speed up discovery and development of the next generation of advanced polymeric materials. We have focused on the high‐throughput automated synthesis of multiblock copolymers that comprise three or more distinct polymer segments of different monomer composition bonded in linear sequence. The present work has exploited automation to prepare high molar mass multiblock copolymers (typically>100,000 g mol−1) using reversible addition‐fragmentation chain transfer (RAFT) polymerization in aqueous emulsion. A variety of original multiblock copolymers have been synthesised via a Chemspeed robot, exemplified by a multiblock copolymer comprising thirteen constituent blocks. Moreover, libraries of copolymers of randomized monomer compositions (acrylates, acrylamides, methacrylates, and styrenes), block orders, and block lengths were also generated, thereby demonstrating the robustness of our synthetic approach. One multiblock copolymer contained all four monomer families listed in the pool, which is unprecedented in the literature. The present work demonstrates that automation has the power to render complex and laborious syntheses of such unprecedented materials not just possible, but facile and straightforward, thus representing the way forward to the next generation of complex macromolecular architectures.
Site‐ and Stereoselective Glycomodification of Biomolecules through Carbohydrate‐Promoted Pictet–Spengler Reaction
Authors: Liu Bo , Zou Xiangman , Zhang Yue , Yang Yang , Xu Hao , Tang Feng , Yu Huixin , Xia Fei , Liu Zhi , Zhao Jianwei , Shi Wei , Huang Wei 
Published: February 2024

AbstractCarbohydrates play pivotal roles in an array of essential biological processes and are consequently involved in many diseases. To meet the needs of glycobiology research, chemical enzymatic and non‐enzymatic methods have been developed to generate glycoconjugates with well‐defined structures. Herein, harnessing the unique properties of C6‐oxidized glycans, we report a straightforward and robust strategy for site‐ and stereoselective glycomodification of biomolecules with N‐terminal tryptophan residues by a carbohydrate‐promoted Pictet–Spengler reaction, which is not adapted to typical aldehyde substrates under biocompatible conditions. This method reliably delivers highly homogeneous glycoconjugates with stable linkages and thus has great potential for functional modulation of peptides and proteins in glycobiology research. Moreover, this reaction can be performed at the glycosites of glycopeptides, glycoproteins and living‐cell surfaces in a site‐specific manner. Control experiments indicated that the protected α‐O atom of aldehyde donors and free N−H bond of the tryptamine motif are crucial for this reaction. Mechanistic investigations demonstrated that the reaction exhibited a first‐order dependence on both tryptophan and glycan, and deprotonation/rearomatization of the pentahydro‐β‐carbolinium ion intermediate might be the rate‐determining step.
Pterion variation in the skulls of rhesus macaques from Cayo Santiago: Inheritance, development, and pathology
Authors: Francis George , Wang Qian 
Published: February 2024

AbstractThe pterion is the sutural juncture of the frontal, parietal, sphenoidal, temporal, and zygomatic bones on the lateral aspect of the cranium. As a craniometric landmark, the pterion has a taxonomic valence, in addition to a common neurosurgical entry point in medicine. Variation in the articulation patterns at the pterion have been documented between primate species yet have a high degree of uniformity within species, suggesting a genetic control for this complex region of the skull. In this study, pterion pattern variation was investigated in 1627 Rhesus macaque crania of the Cayo Santiago colony. The colony's associated skeletal collections accompany known age, sex, and maternal lineages. Pterion pattern prevalence rates were tested against matrilines, as well as cranial shape, and cranial sutural fusion ages (including individuals with prematurely fused sutures). Five patterns were identified, the most prominent being the prevailing Old World Monkey frontotemporal (FT) articulation (83.4%). The relative frequency of those not exhibiting the FT pattern was found to vary considerably between matrilineal families (p = 0.037), ranging from 5.3% to 34.2%. Mothers with the non‐FT pterion pattern were three times as likely to bear non‐FT offspring. Cranial shape additionally varied with pterion type. Males exhibiting zygomaticotemporal (ZT) and sphenoparietal (SP) articulations possessed a relatively longer and narrower cranium than those with the default FT type (p = < 0.001). Cranial sutural fusion ages were not found to differ between pterion types, though all individuals with craniosynostosis (6; 0.38%) exhibited the FT type. The study provided strong evidence for a genetic source for pterion pattern as well as outlining a relatively novel relationship with cranial shape and sutural fusion ages. A unifying explanation may lie in those genes involved in both sutural and craniofacial development, or in the variation of brain growth processes channeling sutural articulation at the pterion. Both may be heritable and responsible for producing observed matrilineal differences in the pterion.
Comparative analysis of osteoderms across the lizard body
Authors: Maliuk Anastasiia , Marghoub Arsalan , Williams Catherine J. A. , Stanley Edward , Kéver Loïc , Vickaryous Matthew , Herrel Anthony , Evans Susan E. , Moazen Mehran 
Published: February 2024

AbstractOsteoderms (ODs) are mineralized tissue embedded within the skin and are particularly common in reptiles. They are generally thought to form a protective layer between the soft tissues of the animal and potential external threats, although other functions have been proposed. The aim of this study was to characterize OD variation across the lizard body. Adults of three lizard species were chosen for this study. After whole body CT scanning of each lizard, single ODs were extracted from 10 different anatomical regions, CT scanned, and characterized using sectioning and nanoindentation. Morphological analysis and material characterization revealed considerable diversity in OD structure across the species investigated. The scincid Tiliqua gigas was the only studied species in which ODs had a similar external morphology across the head and body. Greater osteoderm diversity was found in the gerrhosaurid Broadleysaurus major and the scincid Tribolonotus novaeguineae. Dense capping tissue, like that reported for Heloderma, was found in only one of the three species examined, B. major. Osteoderm structure can be surprisingly complex and variable, both among related taxa, and across the body of individual animals. This raises many questions about OD function but also about the genetic and developmental factors controlling OD shape.
A preoperative magnetic resonance imaging can aid in staging and treatment choice for upper tract urothelial carcinoma
Authors: Almås Bjarte , Reisæter Lars Anders Rokne , Markhus Carl Erik , Hjelle Karin Margrethe , Børretzen Astrid , Beisland Christian 
Published: February 2024

AbstractObjectivesThe aim was to investigate the predictive abilities of a preoperative diffusion‐weighted MRI (dwMRI) among patients with surgically treated upper tract urothelial carcinoma (UTUC).Materials and methodsWritten consent was obtained from all participants in this prospective and ethically approved study. Thirty‐five UTUC patients treated with radical surgery were examined with a preoperative dwMRI and prospectively included during 2017–2022. Two radiologists examined the CT scans and dwMRIs for radiological stage, and the apparent diffusion coefficient (ADC) in the tumours at the dwMRI was registered. The radiologists were blinded for patient history, final histopathology and the readings of the other radiologist. The radiological variables were analysed regarding their abilities to predict muscle‐invasive disease (MID, T2–T4) and tumour grade at final pathology after radical surgery. The predictive abilities were assessed using chi‐square tests, Student's t‐test and calculating the area under the curve in a receiver operating characteristic (ROC) curve. Correlation between the two radiologists was quantified calculating the intra‐class correlation coefficient. P‐values <0.05 were considered statistically significant.ResultsMean age was 72 years, 20 had high‐grade tumour, and 13 patients had MID. The ADC values at the dwMRI were significantly lower among patients with MID compared to patients with non‐muscle‐invasive disease (930 vs 1189, p = <0.001). The area under the ROC curve (AUC) in an ROC curve to predict MID was 0.88 (CI 0.77–0.99, p = <0.001). The ADC values were significantly lower among patients with high‐grade tumours compared to low‐grade tumours (1005 vs 1210, p = 0.002). The correlation of the ADC measurements between the two radiologists was of 0.93 (CI 0.85–0.96, p < 0.001).ConclusionTumour ADC at the MRI emerges as a potential biomarker for aggressive disease. The results are promising but should be validated in a larger, multicentre study.
Widening Participation in Scotland 1997–2021: A semi‐systematic literature review and avenues for further research
Authors: O'Toole Michelle , Dunnett Susan , Brennan Mary , Calvard Thomas , Fakeyeva Liudmila 
Published: February 2024

AbstractThis article sets out and critically analyses the state of current knowledge on Widening Participation at higher education institutions in Scotland and sets forth avenues for further research. Through a semi‐systematic review of the literature, six discrete but overlapping themes relating to Widening Participation are identified, namely, (1) factors affecting the decision to apply to university, (2) the transition from high school or further education into university, (3) contextualised admissions, (4) completion and level of attainment, (5) economic, social and cultural capital and (6) equality, diversity and inclusion. The study finds that while clear progress has been made by higher education institutionstowards achieving quantitative government targets for student recruitment from underrepresented groups, there is an absence of studies and knowledge about the qualitative lived experiences of students as they transition through university, how students negotiate a sense of fit with institutional systems, and what targeted supports they may require to succeed. Avenues for further research which addresses these gaps in the knowledge base are put forward, namely, (1) broaden the academic base and interdisciplinarity of Widening Participation research, (2) reform and extend measures of success beyond admissions and attainment, (3) evolve institutional level support for transition into higher education, (4) develop more nuanced understandings of contextualised admissions and (5) investigate and gain deeper understandings of how the lived experiences of Widening Participation students shape and inform their journey through, experience of and attainment at university.
Incorporating social validity into practice: Treatment progression across pediatric feeding skill domains
Authors: Taylor Tessa , Taylor Sarah Ann 
Published: February 2024

AbstractA small but growing body of research in pediatric feeding disorders asserts the importance of comprehensively measuring social significance of goals, procedures, and effects of intervention, and incorporating social validity into practice to inform treatment. This report sought to extend this literature by detailing procedures to measure and improve social validity during a clinical case of a 3.5‐year‐old during a home‐based intensive feeding program. A multiple baseline design demonstrated effectiveness of nonremoval and re‐presentation added to a treatment package. Repeated choice via direct child preference assessments informed demand fading and gradual progression across six feeding skill domains (medication, cup drinking, independence, texture, volume, variety) and arrangements of response effort (preference, skill) with layers of reinforcer parameters (quality, magnitude, rate, immediacy). Indices of happiness definitions were modified, and extinction bursts examined. Fostering a collaborative approach, caregivers provided detailed input on social validity measures pretreatment, at discharge, and long‐term follow‐up (6‐month, 1‐year), inclusive of both qualitative and quantitative responses, written and verbal communication, and permanent product data. Further implications for practitioners included detailing the process for caregiver training and generalization to family meals with siblings and community settings, and providing adaptable full‐text guidelines for free access/choice contexts.
Phase I study of sapanisertib (CB‐228/TAK‐228/MLN0128) in combination with ziv‐aflibercept in patients with advanced solid tumors
Authors: Coleman Niamh , Stephen Bettzy , Fu Siqing , Karp Daniel , Subbiah Vivek , Ahnert Jordi Rodon , Piha‐Paul Sarina A. , Wright John , Fessahaye Senait N. , Ouyang Fengying , Yilmaz Bulent , Meric‐Bernstam Funda , Naing Aung 
Published: February 2024

AbstractBackgroundSapanisertib is a potent ATP‐competitive, dual inhibitor of mTORC1/2. Ziv‐aflibercept is a recombinant fusion protein comprising human VEGF receptor extracellular domains fused to human immunoglobulin G1. HIF‐1α inhibition in combination with anti‐angiogenic therapy is a promising anti‐tumor strategy. This Phase 1 dose‐escalation/expansion study assessed safety/ tolerability of sapanisertib in combination with ziv‐aflibercept in advanced solid tumors.MethodsFifty‐five patients with heavily pre‐treated advanced metastatic solid tumors resistant or refractory to standard treatment received treatment on a range of dose levels.ResultsFifty‐five patients were enrolled and treated across a range of dose levels. Forty were female (73%), median age was 62 (range: 21–79), and ECOG PS was 0 (9, 16%) or 1 (46, 84%). Most common tumor types included ovarian (8), colorectal (8), sarcoma (8), breast (3), cervical (4), and endometrial (4). Median number of prior lines of therapy was 4 (range 2–11). Sapanisertib 4 mg orally 3 days on and 4 days off plus 3 mg/kg ziv‐aflibercept IV every 2 weeks on a 28‐day cycle was defined as the maximum tolerated dose. Most frequent treatment‐related grade ≥2 adverse events included hypertension, fatigue, anorexia, hypertriglyceridemia, diarrhea, nausea, mucositis, and serum lipase increase. There were no grade 5 events. In patients with evaluable disease (n = 50), 37 patients (74%) achieved stable disease (SD) as best response, two patients (4%) achieved a confirmed partial response (PR); disease control rate (DCR) (CR + SD + PR) was 78%.ConclusionThe combination of sapanisertib and ziv‐aflibercept was generally tolerable and demonstrated anti‐tumor activity in heavily pre‐treated patients with advanced malignancies.
Incidence of immunotherapy‐related hyperprogressive disease (HPD) across HPD definitions and cancer types in observational studies: A systematic review and meta‐analysis
Authors: Kim Min Jeong , Hong Seung Pyo D. , Park Yeonggyeong , Chae Young Kwang 
Published: February 2024

AbstractBackgroundWhile evidence of hyperprogressive disease (HPD) continues to grow, the lack of a consensual definition obscures a proper characterization of HPD incidence. We examined how HPD incidence varies by the tumor type or the type of definition used.MethodsWe searched PubMed, Embase, the Cochrane Library of Systematic Reviews, and Web of Science from database inception to June 21, 2022. Observational studies reporting HPD incidence, in patients diagnosed with solid malignant tumors and treated with immune checkpoint inhibitors (ICI), were included. Random‐effects meta‐analyses were performed, and all statistical tests were 2‐sided.ResultsHPD incidence was 12.4% (95% CI 10.2%–15.0%) with evidence of heterogeneity (Q = 119.32, p < 0.001). Meta‐regression showed that the risk of developing HPD was higher in patients with advanced gastric cancer (adjusted odds ratio [OR], 10.83; 95% CI, 2.14–54.65; p < 0.001), hepatocellular carcinoma (adjusted OR, 7.99; 95% CI, 1.68–38.13; p = 0.006), non‐small cell lung cancer (adjusted OR, 7.14; 95% CI, 1.58–32.29; p = 0.005), and mixed or other types (adjusted OR, 5.09; 95% CI, 1.12–23.14, p = 0.018) than in patients with renal cell carcinoma. Across definitions, HPD defined as a tumor growth kinetics ratio ≥ 2 (adjusted OR, 1.82; 95% CI, 1.08–3.07; p = 0.025) based on the Response Evaluation Criteria in Solid Tumors (RECIST) reported higher incidence than when HPD was defined as RECIST‐defined progressive disease and a change in the tumor growth rate (TGR) exceeding 50% (∆TGR > 50).ConclusionsThe incidence of immunotherapy‐related HPD may vary across tumor types and definitions used, supporting the argument for a uniform and improved method of HPD evaluation for informed clinical decision‐making.
What do cancer patients experience of the simultaneous care clinic? Results of a cross‐sectional study on patient care satisfaction
Authors: Galiano Antonella , Feltrin Alessandra , Pambuku Ardi , Lo Mauro Leda , De Toni Chiara , Murgioni Sabina , Soldà Caterina , Maruzzo Marco , Bergamo Francesca , Brunello Antonella , Zagonel Vittorina 
Published: February 2024

AbstractBackgroundVeneto Institute of Oncology has activated a simultaneous care outpatient clinic (SCOC) in which cancer patients with advanced‐stage cancer are evaluated by oncologist and palliative care specialists. This cross‐sectional study investigated patients' perceptions of the quality of this service.Materials and MethodsAn ad‐hoc self‐administered questionnaire, developed by SCOC team, was used to assess the satisfaction of patients admitted at SCOC consultation. The questionnaire, in addition to the socio‐demographic questions, contains eight questions with the Likert scale: time dedicated, feel listened to, feel understood, feel free to speak openly and to express doubts and concerns, feeling about information and indication received, level of empathy of health care and quality of the relationship, level of professional/quality of performance and utility of consultation, and one open‐ended question. The questionnaire has been proposed to all 174 consecutively admitted patients at SCOC.ResultsOne hundred and sixty‐two patients filled in the questionnaire: 66.7% were male, median age was 71 years, 88.3% had metastatic disease. The time dedicated to SCOC consultation was judged more than adequate (55%) or adequate (35%) by 90% of subjects. Patients completely satisfied about being listened to were 92.5%, with 80.9% being completely satisfied with understanding of their issues and 92% with the freedom to speak and express doubts. Usefulness of the SCOC was rated as excellent by 40% and good by 54.4% of patients. No statistically significant differences were observed in the responses to the questions by gender, age (< or ≥70 years old) and type of tumor.ConclusionOur study shows high levels of satisfactions after SCOC consultation in advanced cancer subjects. Patients' feedback confirmed that SCOC model was effective in helping them during their treatment journey and decision at the end of life. This study encouraged us to enhance our practice of SCOC consultation.Implications for PracticeA joint evaluation of patients living with cancer by oncologist and palliative care team (SCOC‐embedded model), has shown to enhance patients' experience/satisfaction with care‐such as listening, understanding, receiving information, symptom control, and decision about future, independently of age, gender, and kind of tumor.
Efficacy and safety of camrelizumab combined with oxaliplatin and S‐1 as neoadjuvant treatment in locally advanced gastric or gastroesophageal junction cancer: A phase II, single‐arm study
Authors: Zhong Wen‐Jin , Lin Jian‐An , Wu Chu‐Ying , Wang Jian‐Tian , Chen Jun‐Xing , Zheng Hui‐Da , Ye Kai 
Published: February 2024

AbstractPurposeIn the present study, we aimed to evaluate the efficacy and safety of camrelizumab combined with oxaliplatin plus S‐1 in patients with resectable gastric or gastroesophageal junction cancer.MethodsIn this single‐arm, phase II clinical trial, patients with locally advanced gastric or gastroesophageal junction adenocarcinoma were enrolled to receive three cycles of neoadjuvant camrelizumab and oxaliplatin plus S‐1 every 3 weeks, followed by surgical resection and adjuvant therapy with the same regimen. The primary endpoint was pathological complete response (pCR) (ypT0) rate and secondary endpoints were R0 resection rate, total pCR (tpCR, ypT0N0) rate, major pathological response (MPR) rate, downstaging, objective response rate (ORR), disease control rate (DCR), event‐free survival (EFS), overall survival (OS), and safety.ResultsBetween September, 2020 and January, 2022, a total of 29 patients were enrolled in the present study, all of whom completed neoadjuvant therapy and underwent surgery. Three (10.3%) (95% CI: 2.2–27.4) patients achieved pCR as well as tpCR, 20 (69.0%) patients had MPR and 28 (96.6%) patients achieved R0 resection. Treatment‐emergent adverse events (AEs) of any grade were observed in 24 (82.8%) patients. Immune‐related adverse events of any grade were reported in 13 (44.8%) patients, whereas no grade 3 or higher adverse events occurred.ConclusionThe neoadjuvant therapy with camrelizumab in combination with oxaliplatin and S‐1 showed a modest pCR rate, and favorable MPR rate and safety profile in patients with gastric or gastroesophageal junction cancer.
Neighborhood social vulnerability and disparities in time to kidney cancer surgical treatment and survival in Arizona
Authors: Valencia Celina I. , Wightman Patrick , Morrill Kristin E. , Hsu Chiu‐Hsieh , Arif‐Tiwari Hina , Kauffman Eric , Gachupin Francine C. , Chipollini Juan , Lee Benjamin R. , Garcia David O. , Batai Ken 
Published: February 2024

AbstractBackgroundHispanics and American Indians (AI) have high kidney cancer incidence and mortality rates in Arizona. This study assessed: (1) whether racial and ethnic minority patients and patients from neighborhoods with high social vulnerability index (SVI) experience a longer time to surgery after clinical diagnosis, and (2) whether time to surgery, race and ethnicity, and SVI are associated with upstaging to pT3/pT4, disease‐free survival (DFS), and overall survival (OS).MethodsArizona Cancer Registry (2009–2018) kidney and renal pelvis cases (n = 4592) were analyzed using logistic regression models to assess longer time to surgery and upstaging. Cox‐regression hazard models were used to test DFS and OS.ResultsHispanic and AI patients with T1 tumors had a longer time to surgery than non‐Hispanic White patients (median time of 56, 55, and 45 days, respectively). Living in neighborhoods with high (≥75) overall SVI increased odds of a longer time to surgery for cT1a (OR 1.54, 95% CI: 1.02–2.31) and cT2 (OR 2.32, 95% CI: 1.13–4.73). Race and ethnicity were not associated with time to surgery. Among cT1a patients, a longer time to surgery increased odds of upstaging to pT3/pT4 (OR 1.95, 95% CI: 0.99–3.84). A longer time to surgery was associated with PFS (HR 1.52, 95% CI: 1.17–1.99) and OS (HR 1.63, 95% CI: 1.26–2.11). Among patients with cT2 tumor, living in high SVI neighborhoods was associated with worse OS (HR 1.66, 95% CI: 1.07–2.57).ConclusionsHigh social vulnerability was associated with increased time to surgery and poor survival after surgery.