bluuebunny/crossref_metadata_2025 huggingface dataset:
Diene Salts of the Adamantane Series: Synthesis, Structure, and Chemical Transformations
Authors: Bogdanova Anastasiya N. , Baimuratov Marat R. , Polyakova Polina A. , Shiryaev Vadim A. , Klimochkin Yuri N.
Published: February 2024

Mono‐ and bis‐pyridinium, phosphonium and sulfonium allylic salts, containing adamantane fragment, have been obtained from the substitution reaction in 1,4‐dibromo‐2‐butene. It was found, that the attack of triethylamine undergoes from the sterically less hindered side, leading to deprotonation and subsequent elimination of the molecular fragment with the formation of a new salt of diene structure. Quantum chemical calculations were used to confirm the structure of one of the products by correlation analysis of experimental and calculated NMR data that confirmed the s‐cisoid conformation of the diene. It was found, that obtained dienes may be used as substrates in Diels‐Alder reaction despite their high sterical hinderance.
Information fusion for infant age estimation from deciduous teeth using machine learning
Authors: Martínez‐Moreno Práxedes , Valsecchi Andrea , Damas Sergio , Irurita Javier , Mesejo Pablo
Published: February 2024

Objectives

Over the past few years, several methods have been proposed to improve the accuracy of age estimation in infants with a focus on dental development as a reliable marker. However, traditional approaches have limitations in efficiently combining information from different teeth and features. In order to address these challenges, this article presents a study on age estimation in infants with Machine Learning (ML) techniques, using deciduous teeth.

Materials and Methods

The involved dataset comprises 114 infant skeletons from the Granada osteological collection of identified infants, aged between 5 months of gestation and 3 years of age. The samples consist of features such as the maximum length and mineralization and alveolar stages of teeth. For the purpose of designing a method capable of combining all the information available from each individual, a Multilayer Perceptron model is proposed, one of the most popular artificial neural networks. This model has been validated using the leave‐one‐out experimental validation protocol. Through different groups of experiments, the study examines the informativeness of the aforementioned features, individually and in combination.

Results

The results indicate that the fusion of different variables allows for more accurate age estimates (RMSE = 66 days) than when variables are analyzed separately (RMSE = 101 days). Additionally, the study demonstrates the benefits of involving multiple teeth, which significantly reduces the RMSE compared to a single tooth.

Discussion

This article underlines the clear advantages of ML‐based methods, emphasizing their potential to improve the accuracy and robustness when estimating the age of infants.
Neighborhood disadvantage reduces cognitive reserve independent of neuropathologic change
Authors: Kim Boram , Yannatos Isabel , Blam Kaitlin , Wiebe Douglas , Xie Sharon X. , McMillan Corey T. , Mechanic‐Hamilton Dawn , Wolk David A. , Lee Edward B.
Published: February 2024

INTRODUCTION

Individuals in socioeconomically disadvantaged neighborhoods exhibit increased risk for impaired cognitive function. Whether this association relates to the major dementia‐related neuropathologies is unknown.

METHODS

This cross‐sectional study included 469 autopsy cases from 2011 to 2023. The relationships between neighborhood disadvantage measured by Area Deprivation Index (ADI) percentiles categorized into tertiles, cognition evaluated by the last Mini‐Mental State Examination (MMSE) scores before death, and 10 dementia‐associated proteinopathies and cerebrovascular disease were assessed using regression analyses.

RESULTS

Higher ADI was significantly associated with lower MMSE score. This was mitigated by increasing years of education. ADI was not associated with an increase in dementia‐associated neuropathologic change. Moreover, the significant association between ADI and cognition remained even after controlling for changes in major dementia‐associated proteinopathies or cerebrovascular disease.

DISCUSSION

Neighborhood disadvantage appears to be associated with decreased cognitive reserve. This association is modified by education but is independent of the major dementia‐associated neuropathologies.
Patient‐ and proxy‐reported quality of life in advanced dementia with Lewy bodies
Authors: Armstrong Melissa J. , LaBarre Brian , Sovich Kaitlin , Maixner Susan M. , Paulson Henry L. , Manning Carol , Fields Julie A. , Lunde Angela , Forsberg Leah , Boeve Bradley F. , Galvin James E. , Taylor Angela S. , Li Zhigang
Published: February 2024

INTRODUCTION

Little is known regarding quality of life (QoL) in dementia with Lewy bodies (DLB), particularly in advanced stages.

METHODS

Dyads of individuals with moderate–advanced DLB and their primary caregivers were recruited from specialty clinics, advocacy organizations, and research registries. The study collected demographics, disease‐related measures, and measures of patient/caregiver experiences.

RESULTS

The Quality of Life in Alzheimer's Disease (QoL‐AD) was completed by the person with DLB and the caregiver (proxy) in 61 dyads; 85 dyads had only a proxy‐completed QoL‐AD. Patient‐ and proxy‐reported scores were moderately correlated (r = 0.57, P < 0.0001). Worse patient‐reported QoL correlated with daytime sleepiness, autonomic symptom burden, and behavioral symptoms. Proxy ratings correlated with dementia severity, daytime sleepiness, behavioral symptoms, dependence in activities of daily living, and caregiver experience measures.

DISCUSSION

Patient‐ and proxy‐reported quality of life (QoL) should be assessed separately in advanced DLB. Some symptoms associated with QoL have available therapeutic options. Research is needed regarding strategies to optimally improve QoL in DLB.

Highlights

Patient and proxy quality of life (QoL) ratings had moderate correlation in advanced dementia with Lewy bodies.

Daytime sleepiness affected patient‐ and proxy‐reported QoL.

Behavioral symptoms affected patient‐ and proxy‐reported QoL.

Autonomic symptom burden affected patient‐reported QoL.

Dementia severity, dependence, and caregiver experiences affected proxy ratings.
Conditional knockout of the NSD2 gene in mouse intestinal epithelial cells inhibits colorectal cancer progression
Authors: Li Mengyuan , Chen Hanxue , Yang Xingjiu , Zhang Wenlong , Ma Chengyan , Wang Qinghong , Wang Xinpei , Gao Ran
Published: February 2024

Background

Nuclear receptor‐binding SET domain 2 (NSD2) is a histone methyltransferase, that catalyzes dimethylation of lysine 36 of histone 3 (H3K36me2) and is associated with active transcription of a series of genes. NSD2 is overexpressed in multiple types of solid human tumors and has been proven to be related to unfavorable prognosis in several types of tumors.

Methods

We established a mouse model in which the NSD2 gene was conditionally knocked out in intestinal epithelial cells. We used azoxymethane and dextran sodium sulfate to chemically induce murine colorectal cancer. The development of colorectal tumors were investigated using post‐necropsy quantification, immunohistochemistry, and enzyme‐linked immunosorbent assay (ELISA).

Results

Compared with wild‐type (WT) control mice, NSD2fl/fl‐Vil1‐Cre mice exhibited significantly decreased tumor numbers, histopathological changes, and cytokine expression in colorectal tumors.

Conclusions

Conditional knockout of NSD2 in intestinal epithelial cells significantly inhibits colorectal cancer progression.
Ictal Central Apnea Is Predictive of Mesial Temporal Seizure Onset: An Intracranial Investigation
Authors: Lacuey Nuria , Talavera Blanca , Magana‐Tellez Oman , Mancera‐Páez Oscar , Hupp Norma , Luo Xi , Hampson Johnson P. , Hampson Jaison , Rani M. R. Sandhya , Ochoa‐Urrea Manuela , Alamoudi Omar A. , Melius Stephen , Pati Sandipan , Gavvala Jay , Tandon Nitin , Mosher John C. , Lhatoo Samden D.
Published: February 2024

Objective

Ictal central apnea (ICA) is a semiological sign of focal epilepsy, associated with temporal and frontal lobe seizures. In this study, using qualitative and quantitative approaches, we aimed to assess the localizational value of ICA. We also aimed to compare ICA clinical utility in relation to other seizure semiological features of focal epilepsy.

Methods

We analyzed seizures in patients with medically refractory focal epilepsy undergoing intracranial stereotactic electroencephalographic (SEEG) evaluations with simultaneous multimodal cardiorespiratory monitoring. A total of 179 seizures in 72 patients with reliable artifact‐free respiratory signal were analyzed.

Results

ICA was seen in 55 of 179 (30.7%) seizures. Presence of ICA predicted a mesial temporal seizure onset compared to those without ICA (odds ratio = 3.8, 95% confidence interval = 1.3–11.6, p = 0.01). ICA specificity was 0.82. ICA onset was correlated with increased high‐frequency broadband gamma (60–150Hz) activity in specific mesial or basal temporal regions, including amygdala, hippocampus, and fusiform and lingual gyri. Based on our results, ICA has an almost 4‐fold greater association with mesial temporal seizure onset zones compared to those without ICA and is highly specific for mesial temporal seizure onset zones. As evidence of symptomatogenic areas, onset‐synchronous increase in high gamma activity in mesial or basal temporal structures was seen in early onset ICA, likely representing anatomical substrates for ICA generation.

Interpretation

ICA recognition may help anatomoelectroclinical localization of clinical seizure onset to specific mesial and basal temporal brain regions, and the inclusion of these regions in SEEG evaluations may help accurately pinpoint seizure onset zones for resection. ANN NEUROL 2024;95:998–1008
Increased Cortical Thickness in Alzheimer's Disease
Authors: Phan Tony X. , Baratono Sheena , Drew William , Tetreault Aaron M. , Fox Michael D. , Darby R. Ryan ,   For the Alzheimer's Disease Neuroimaging Initiative,   for the Alzheimer's Disease Metabolomics Consortium
Published: February 2024

Objective

Patients with Alzheimer's disease (AD) have diffuse brain atrophy, but some regions, such as the anterior cingulate cortex (ACC), are spared and may even show increase in size compared to controls. The extent, clinical significance, and mechanisms associated with increased cortical thickness in AD remain unknown. Recent work suggested neural facilitation of regions anticorrelated to atrophied regions in frontotemporal dementia. Here, we aim to determine whether increased thickness occurs in sporadic AD, whether it relates to clinical symptoms, and whether it occur in brain regions functionally connected to—but anticorrelated with—locations of atrophy.

Methods

Cross‐sectional clinical, neuropsychological, and neuroimaging data from the Alzheimer's Disease Neuroimaging Initiative were analyzed to investigate cortical thickness in AD subjects versus controls. Atrophy network mapping was used to identify brain regions functionally connected to locations of increased thickness and atrophy.

Results

AD patients showed increased thickness in the ACC in a region‐of‐interest analysis and the visual cortex in an exploratory analysis. Increased thickness in the left ACC was associated with preserved cognitive function, while increased thickness in the left visual cortex was associated with hallucinations. Finally, we found that locations of increased thickness were functionally connected to, but anticorrelated with, locations of brain atrophy (r = −0.81, p < 0.05).

Interpretation

Our results suggest that increased cortical thickness in Alzheimer's disease is relevant to AD symptoms and preferentially occur in brain regions functionally connected to, but anticorrelated with, areas of brain atrophy. Implications for models of compensatory neuroplasticity in response to neurodegeneration are discussed. ANN NEUROL 2024;95:929–940
COF‐Topological Quantum Material Nano‐heterostructure for CO2 to Syngas Production under Visible Light
Authors: Dey Anupam , Pradhan Jayita , Biswas Sandip , Ahamed Rahimi Faruk , Biswas Kanishka , Maji Tapas Kumar
Published: February 2024

Efficient solar‐driven syngas production (CO+H2 mixture) from CO2 and H2O with a suitable photocatalyst and fundamental understanding of the reaction mechanism are the desired approach towards the carbon recycling process. Herein, we report the design and development of an unique COF‐topological quantum material nano‐heterostructure, COF@TI with a newly synthesized donor‐acceptor based COF and two dimensional (2D) nanosheets of strong topological insulator (TI), PbBi2Te4. The intrinsic robust metallic surfaces of the TI act as electron reservoir, minimising the fast electron‐hole recombination process, and the presence of 6s2 lone pairs in Pb2+ and Bi3+ in the TI helps for efficient CO2 binding, which are responsible for boosting overall catalytic activity. In variable ratio of acetonitrile‐water (MeCN : H2O) solvent mixture COF@TI produces syngas with different ratios of CO and H2. COF@TI nano‐heterostructure enables to produce higher amount of syngas with more controllable ratios of CO and H2 compared to pristine COF. The electron transfer route from COF to TI was realized from Kelvin probe force microscopy (KPFM) analysis, charge density difference calculation, excited state lifetime and photoelectrochemical measurements. Finally, a probable mechanistic pathway has been established after identifying the catalytic sites and reaction intermediates by in situ DRIFTS study and DFT calculation.
Nanoscale Local Contacts Enable Inverted Inorganic Perovskite Solar Cells with 20.8 % Efficiency
Authors: Wang Sanlong , Qi Shanshan , Sun Hongrui , Wang Pengyang , Zhao Ying , Zhang Xiaodan
Published: February 2024

Inorganic perovskite solar cells (IPSCs) have gained significant attention due to their excellent thermal stability and suitable band gap (~1.7 eV) for tandem solar cell applications. However, the defect‐induced non‐radiative recombination losses, low charge extraction efficiency, energy level mismatches, and so on render the fabrication of high‐efficiency inverted IPSCs remains challenging. Here, the use of 3‐amino‐5‐bromopyridine‐2‐formamide (ABF) in methanol was dynamically spin‐coated on the surface of CsPbI2.85Br0.15 film, which facilitates the limited etching of defect‐rich subsurface layer, resulting in the formation of vertical PbI2 nanosheet structures. This enabled localized contacts between the perovskite film and the electron transport layer, suppress the recombination of electron‐hole and beneficial to electron extraction. Additionally, the C=O and C=N groups in ABF effectively passivated the undercoordinated Pb2+ at grain boundaries and on the surface of CsPbI2.85Br0.15 film. Eventually, we achieved a champion efficiency of 20.80 % (certified efficiency of 20.02 %) for inverted IPSCs with enhanced stability, which is the highest value ever reported to date. Furthermore, we successfully prepared p‐i‐n type monolithic inorganic perovskite/silicon tandem solar cells (IPSTSCs) with an efficiency of 26.26 %. This strategy provided both fast extraction and efficient passivation at the electron‐selective interface.
Non‐Directed C−H Arylation of Anisole Derivatives via Pd/S,O‐Ligand Catalysis
Authors: Deng Ke‐Zuan , Sukowski Verena , Fernández‐Ibáñez M. Ángeles
Published: February 2024

Non‐directed C−H arylation is one of the most efficient methods to synthesize biaryl compounds without the need of the prefuctionalization of starting materials, or the installment and removal of directing groups on the substrate. A direct C−H arylation of simple arenes as limiting reactants remains a challenge. Here we disclose a non‐directed C−H arylation of anisole derivatives as limiting reagents with aryl iodides under mild reaction conditions. The arylated products are obtained in synthetically useful yields and the arylation of bioactive molecules is also demonstrated. Key to the success of this methodology is the use of a one‐step synthesized S,O‐ligand.
Expanding Luminescence Horizons in Macropolyhedral Heteroboranes
Authors: Bould Jonathan , Ehn Marcel , Tok Oleg , Bavol Dmytro , Kučeráková Monika , Clegg William , Litecká Miroslava , Lang Kamil , Kirakci Kaplan , Londesborough Michael G. S.
Published: February 2024

Luminescence is observed in three novel macropolyhedral nineteen‐ and eighteen‐vertex chalcogenaboranes: Se2B17H17 (1), SeB17H19 (3) and SeB18H20 (4). This led us to the recognition that previously published macropolyhedral heteroborane species might also exhibit luminescence. Thus, the known nineteen‐ and eighteen‐vertex dithiaboranes S2B17H17 (2), n‐S2B16H16 (5) and i‐S2B16H16 (6) were synthesised and also found to exhibit a range of luminescent properties. These macropolyhedral species are very different from the previously unique fluorescent binary borane B18H22 in terms of their structural architectures, by the presence of borane cluster hetero atoms, and, as in the cases of 5 and 6, that their synthetic origins are not derived simply through the modification of B18H22 itself. They consequently greatly expand the possibilities of finding new luminescent inorganic borane species.
Photoluminescence Enhancement in Silica‐Confined Ligand‐Free Perovskite Nanocrystals by Suppression of Silanol‐Induced Traps and Phase Impurities
Authors: Huang Yipeng , Lin Fangyuan , Li Feiming , Jin Jinwen , Guo Zhiyong , Tian Dongjie , Xie Rongjun , Chen Xi
Published: February 2024

The detriments of intrinsic silanol groups in mesoporous silica to the photoluminescence (PL) of lead halide perovskite nanocrystals (LHP NCs) confined in the template have never been determined and clearly elucidated. Here, we disclose that silanol‐induced Cs+ and Br− deficiencies prompt the generation of traps and CsPb2Br5 impurities. The temperature‐dependent PL spectra verify the higher energetic barrier of trap states in CsPbBr3 NCs confined in silanol‐rich mesoporous silica. Femtosecond transient absorption spectra reveal the trapped state mediates a broadband photoinduced absorption and long‐lived decay pathway of CsPbBr3 NCs in silanol‐rich templates. A remarkable improvement (up to 160‐fold) in PL quantum yields is realized by simple silanol elimination. This work demonstrates the detrimental effects of silanol sites on the PL properties of LHP NCs impregnated in mesoporous silica and provides a new perspective for the ligand‐free synthesis of high‐quality LHP NCs in mesoporous templates by facile impregnation for practical applications.
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

Synthetic 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

Carbohydrates 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

The 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

Osteoderms (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

Objectives

The 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 methods

Written 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.

Results

Mean 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).

Conclusion

Tumour 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

This 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

A 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

Background

Sapanisertib 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.

Methods

Fifty‐five patients with heavily pre‐treated advanced metastatic solid tumors resistant or refractory to standard treatment received treatment on a range of dose levels.

Results

Fifty‐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%.

Conclusion

The 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

Background

While 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.

Methods

We 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.

Results

HPD 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).

Conclusions

The 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

Background

Veneto 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 Methods

An 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.

Results

One 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.

Conclusion

Our 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 Practice

A 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

Purpose

In 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.

Methods

In 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.

Results

Between 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.

Conclusion

The 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

Background

Hispanics 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).

Methods

Arizona 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.

Results

Hispanic 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).

Conclusions

High social vulnerability was associated with increased time to surgery and poor survival after surgery.
Accessibility to ERCP‐performing hospitals among patients with pancreatic cancer living in SEER regions
Authors: Tavakkoli Anna , Beauchamp Alaina , Prasad Tanushree , Zhu Hong , Singal Amit G. , Elmunzer B. Joseph , Kubiliun Nisa M. , Kwon Richard S. , Hughes Amy E. , Pruitt Sandi L.
Published: February 2024

Background and Aims

The two most common interventions used to treat painless jaundice from pancreatic cancer are endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic biliary drainage (PTBD). Our study aimed to characterize the geographic distribution of ERCP‐performing hospitals among patients with pancreatic cancer in the United States and the association between geographic accessibility to ERCP‐performing hospitals and biliary interventions patients receive.

Methods

This is a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER)‐Medicare database for pancreatic cancer from 2005 to 2013. Multilevel models were used to examine the association between accessibility to ERCP hospitals within a 30‐ and 45‐min drive from the patient's residential ZIP Code and the receipt of ERCP treatment. A two‐step floating catchment area model was used to calculate the measure of accessibility based on the distribution across SEER regions.

Results

7464 and 782 patients underwent ERCP and PTBD, respectively, over the study period. There were 808 hospitals in which 8246 patients diagnosed with pancreatic cancer in SEER regions from 2005 to 2013 received a procedure. Patients with high accessibility within both 30‐ and 45‐min drive to an ERCP‐performing hospital were more likely to receive an ERCP (30‐min adjusted odds ratio [aOR]: 1.53, 95% confidence interval [CI]: 1.17–2.01; 45‐min aOR: 1.31, 95% CI: 1.01–1.70). Furthermore, in the adjusted model, Black patients (vs. White) and patients with stage IV disease were less likely to receive ERCP than PTBD.

Conclusions

Patients with pancreatic cancer and high accessibility to an ERCP‐performing hospital were more likely to receive ERCP. Disparities in the receipt of ERCP persisted for Black patients regardless of their access to ERCP‐performing hospitals.
Association between personality types and low anterior resection syndrome in rectal cancer patients following surgery
Authors: Chiang Ting‐Yu , Hsu Yu‐Jen , Chern Yih‐Jong , Liao Chun‐Kai , Tsai Wen‐Sy , Hsieh Pao‐Shiu , Hsu Hung‐Chih , Lin Yu‐Fen , Lee Hsiu‐Lan , You Jeng‐Fu
Published: February 2024

Purpose

Low anterior resection syndrome (LARS) has had many impacts on the lives of patients and substantial differences in emotional and social functions. The aim of this study was to investigate the correlation analysis of different personality traits in rectal cancer patients with LARS after undergoing curative surgery.

Methods

This study was designed as a prospective cohort study. The inclusion criteria included (1) participants diagnosed with rectal cancer who underwent surgical resection of malignant tumors and (2) ECOG 0–1. The primary outcome was the correlation between different personality traits and low anterior resection syndrome in rectal cancer patients after radical surgery. Low anterior resection syndrome incidence rates were estimated by questionnaires and personality groups by the Type A and Type D Scale‐14 Personality Inventory.

Results

For all 161 participants in this study, the presence of a tumor at the lower anal verge and the receipt of neoadjuvant CCRT had a statistically significant positive correlation with the LARS score at 1 month, 6 months, and 1 year (Pearson correlation coefficient = −0.283, −0.374, and − 0.205, respectively), with a p value of less than 0.05. Personalities with Type A, Type D, and Type D‐SI scores had a statistically significant positive correlation with LARS score at 1 month (Pearson correlation coefficient = 0.172, 0.162, and 0,164, p value = 0.03, 0.04, and 0.04).

Conclusion

Type A and Type D personalities are highly linked to LARS. Personalized support approaches can ultimately assist rectal cancer patients in overcoming difficulties after surgery and recovery and enhance their functional outcomes.