bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined Single‐Cell and Spatial Transcriptomics Reveal the Metabolic Evolvement of Breast Cancer during Early Dissemination
Authors: Liu Yi‐Ming , Ge Jing‐Yu , Chen Yu‐Fei , Liu Tong , Chen Lie , Liu Cui‐Cui , Ma Ding , Chen Yi‐Yu , Cai Yu‐Wen , Xu Ying‐Ying , Shao Zhi‐Ming , Yu Ke‐Da 
Published: January 2023

AbstractBreast cancer is now the most frequently diagnosed malignancy, and metastasis remains the leading cause of death in breast cancer. However, little is known about the dynamic changes during the evolvement of dissemination. In this study, 65 968 cells from four patients with breast cancer and paired metastatic axillary lymph nodes are profiled using single‐cell RNA sequencing (scRNA‐seq) and spatial transcriptomics. A disseminated cancer cell cluster with high levels of oxidative phosphorylation (OXPHOS), including the upregulation of cytochrome C oxidase subunit 6C and dehydrogenase/reductase 2, is identified. The transition between glycolysis and OXPHOS when dissemination initiates is noticed. Furthermore, this distinct cell cluster is distributed along the tumor's leading edge. The findings here are verified in three different cohorts of breast cancer patients and an external scRNA‐seq dataset, which includes eight patients with breast cancer and paired metastatic axillary lymph nodes. This work describes the dynamic metabolic evolvement of early disseminated breast cancer and reveals a switch between glycolysis and OXPHOS in breast cancer cells as the early event during lymph node metastasis.
Synergistic Mechanism of Sub‐Nanometric Ru Clusters Anchored on Tungsten Oxide Nanowires for High‐Efficient Bifunctional Hydrogen Electrocatalysis
Authors: Pi Yecan , Qiu Ziming , Sun Yi , Ishii Hirofumi , Liao Yen‐Fa , Zhang Xiuyun , Chen Han‐Yi , Pang Huan 
Published: January 2023

AbstractThe construction of strong interactions and synergistic effects between small metal clusters and supports offers a great opportunity to achieve high‐performance and cost‐effective heterogeneous catalysis, however, studies on its applications in electrocatalysis are still insufficient. Herein, it is reported that W18O49 nanowires supported sub‐nanometric Ru clusters (denoted as Ru SNC/W18O49 NWs) constitute an efficient bifunctional electrocatalyst for hydrogen evolution/oxidation reactions (HER and HOR) under acidic condition. Microstructural analyses, X‐ray absorption spectroscopy, and density functional theory (DFT) calculations reveal that the Ru SNCs with an average RuRu coordination number of 4.9 are anchored to the W18O49 NWs via RuOW bonds at the interface. The strong metal‐support interaction leads to the electron‐deficient state of Ru SNCs, which enables a modulated RuH strength. Furthermore, the unique proton transport capability of the W18O49 also provides a potential migration channel for the reaction intermediates. These components collectively enable the remarkable performance of Ru SNC/W18O49 NWs for hydrogen electrocatalysis with 2.5 times of exchange current density than that of carbon‐supported Ru nanoparticles, and even rival the state‐of‐the‐art Pt catalyst. This work provides a new prospect for the development of supported sub‐nanometric metal clusters for efficient electrocatalysis.
Targeting MCL‐1 and BCL‐2 with polatuzumab vedotin and venetoclax overcomes treatment resistance in R/R non‐Hodgkin lymphoma: Results from preclinical models and a Phase Ib study
Authors: Lasater Elisabeth A. , Amin Dhara N. , Bannerji Rajat , Mali Raghuveer Singh , Barrett Kathy , Rys Ryan N. , Oeh Jason , Lin Eva , Sterne‐Weiler Tim , Ingalla Ellen Rei , Go MaryAnn , Yu Shang‐Fan , Krem Maxwell M. , Arthur Chris , Hahn Uwe , Johnston Anna , Karur Vinit , Khan Nadia , Marlton Paula , Phillips Tycel , Gritti Giuseppe , Seymour John F. , Tani Monica , Yuen Sam , Martin Scott , Chang Matthew T. , Rose Christopher M. , Pham Victoria C. , Polson Andrew G. , Chang YiMeng , Wever Claudia , Johnson Nathalie A. , Jiang Yanwen , Hirata Jamie , Sampath Deepak , Musick Lisa , Flowers Christopher R. , Wertz Ingrid E. 
Published: January 2023

AbstractThe treatment of patients with relapsed or refractory lymphoid neoplasms represents a significant clinical challenge. Here, we identify the pro‐survival BCL‐2 protein family member MCL‐1 as a resistance factor for the BCL‐2 inhibitor venetoclax in non‐Hodgkin lymphoma (NHL) cell lines and primary NHL samples. Mechanistically, we show that the antibody‐drug conjugate polatuzumab vedotin promotes MCL‐1 degradation via the ubiquitin/proteasome system. This targeted MCL‐1 antagonism, when combined with venetoclax and the anti‐CD20 antibodies obinutuzumab or rituximab, results in tumor regressions in preclinical NHL models, which are sustained even off‐treatment. In a Phase Ib clinical trial (NCT02611323) of heavily pre‐treated patients with relapsed or refractory NHL, 25/33 (76%) patients with follicular lymphoma and 5/17 (29%) patients with diffuse large B‐cell lymphoma achieved complete or partial responses with an acceptable safety profile when treated with the recommended Phase II dose of polatuzumab vedotin in combination with venetoclax and an anti‐CD20 antibody.
Acute myeloid leukemia: 2023 update on diagnosis, risk‐stratification, and management
Authors: Shimony Shai , Stahl Maximilian , Stone Richard M. 
Published: January 2023

AbstractDisease overviewAcute myeloid leukemia (AML) is a frequently fatal bone marrow stem cell cancer characterized by unbridled proliferation of malignant marrow stem cells with associated infection, anemia, and bleeding. An improved understanding of pathophysiology, improvements in measurement technology and at least 10 recently approved therapies have led to revamping the diagnostic, prognostic, and therapeutic landscape of AML.DiagnosisOne updated and one new classification system were published in 2022, both emphasizing the integration of molecular analysis into daily practice. Differences between the International Consensus Classification and major revisions from the previous 2016 WHO system provide both challenges and opportunities for care and clinical research.Risk assessment and monitoringThe European Leukemia Net 2022 risk classification integrates knowledge from novel molecular findings and recent trial results, as well as emphasizing dynamic risk based on serial measurable residual disease assessment. However, how to leverage our burgeoning ability to measure a small number of potentially malignant myeloid cells into therapeutic decision making is controversial.Risk adapted therapyThe diagnostic and therapeutic complexity plus the availability of newly approved agents requires a nuanced therapeutic algorithm which should integrate patient goals of care, comorbidities, and disease characteristics including the specific mutational profile of the patient's AML. The framework we suggest only represents the beginning of the discussion.
Concurrent de novo ZFHX4 variant and 16q24.1 deletion in a patient with orofacial clefting; a potential role of ZFHX4 and USP10
Authors: Créton Marijn , Wagener Frank , Massink Maarten , Fennis Willem , Bloemen Marjon , Schols Jan , Aarts Miranda , van der Molen Aebele Mink , van Haaften Gijs , van den Boogaard Marie José 
Published: January 2023

AbstractA girl with a unilateral cleft lip, alveolus and palate, tooth agenesis, and mild dysmorphic features, without a specific underlying syndrome diagnosis, was genotypically characterized and phenotypically described. Cleft gene panel analysis, single‐nucleotide polymorphism (SNP) array, whole genome sequencing (WGS), whole exome sequencing, and quantitative PCR (Q‐PCR) analysis were used as diagnostic tests. SNP array revealed a maternal deletion at 16q24.1, encompassing the cleft candidate gene USP10. WES revealed an additional de novo Loss‐of‐Function variant (p.(Asn838fs)) in the Zinc‐Finger‐Homeobox‐4 (ZFHX4) gene. Q‐PCR was performed to explore the effect of the ZFHX4 variant and the deletion in 16q24.1. The mRNA expression of a selection of putative target genes involved in orofacial clefting showed a lowered expression of USP10 (52%), CRISPLD2 (31%), and CRISPLD1 (1%) compared to the control. IRF6 showed no difference in gene expression. This case supports ZFHX4 as a novel cleft gene and suggests USP10 may contribute to the etiology of orofacial clefts in humans.
Data sharing to advance gene‐targeted therapies in rare diseases
Authors: Lekstrom‐Himes Julie , Augustine Erika F. , Brower Amy , Defay Thomas , Finkel Richard S. , McGuire Amy L. , Skinner Mark W. , Yu Timothy W. 
Published: January 2023

AbstractRecent advancements in gene‐targeted therapies have highlighted the critical role data sharing plays in successful translational drug development for people with rare diseases. To scale these efforts, we need to systematize these sharing principles, creating opportunities for more rapid, efficient, and scalable drug discovery/testing including long‐term and transparent assessment of clinical safety and efficacy. A number of challenges will need to be addressed, including the logistical difficulties of studying rare diseases affecting individuals who may be scattered across the globe, scientific, technical, regulatory, and ethical complexities of data collection, and harmonization and integration across multiple platforms and contexts. The NCATS/NIH Gene‐Targeted Therapies: Early Diagnosis and Equitable Delivery meeting series held during June 2021 included data sharing models that address these issues and framed discussions of areas that require improvement. This article describes these discussions and provides a series of considerations for future data sharing.
Wide‐Bandgap Perovskite Solar Cell Using a Fluoride‐Assisted Surface Gradient Passivation Strategy
Authors: Yan Nan , Gao Yan , Yang Junjie , Fang Zhimin , Feng Jiangshan , Wu Xiaojun , Chen Tao , Liu Shengzhong (Frank) 
Published: January 2023

AbstractWide‐band gap (1.68 eV) perovskite solar cells (PSCs) are important components of perovskite/Si tandem devices. However, the efficiency of wide band gap PSCs has been limited by their huge open‐circuit voltage (Voc) deficit due to non‐radiative recombination. Deep‐level acceptor defects are identified as the major killers of Voc, and they can be effectively improved by passivation with ammonium salts. Theoretical calculation predicts that increasing the distance between F and −NH3+ of fluorinated ammonium can dramatically enhance the electropositivity of −NH3+ terminals, thus providing strong adsorption onto the negatively charged IA and IPb anti‐site defects. Characterizations further confirm that surface gradient passivation employing p‐FPEAI demonstrates the most efficient passivation effect. Consequently, a record‐efficiency of 21.63 % with the smallest Voc deficit of 441 mV is achieved for 1.68 eV‐band gap inverted PSCs. Additionally, a flexible PSC and 1 cm2 opaque device also deliver the highest PCEs of 21.02 % and 19.31 %, respectively.
Dual Role of a Fluorescent Small Molecule as a Sensor and Inhibitor of Protein Fibrillation
Authors: Das Anirban , Sah Pooja , Saraogi Ishu 
Published: January 2023

AbstractOrdered fibrillar aggregates of proteins, called amyloids, are prevalent in several diseases like Alzheimer's, Parkinson's, and Type II diabetes. The key challenge in the treatment of such diseases is the early detection of protein fibrillation and its effective inhibition using extrinsic agents. Thus, molecules that can both detect and inhibit protein fibril formation have great diagnostic and therapeutic utility. Using insulin as a model protein, we report the dual action of an isoquinoline based molecule, named MK14 which detects and prevents insulin fibrillation. Dose dependent inhibition of insulin fibrillation by MK14 gave an IC50 value of 9 μM, and mechanistic investigations suggested that MK14 prevented the elongation of fibrils by interacting with pre‐fibrillar intermediates. The fluorescence of MK14 enhanced upon binding to fibrils of insulin as well as those of α‐synuclein, the protein involved in Parkinson's disease. MK14 is an environmentally sensitive fluorophore, which could also detect amorphous aggregates of insulin. The dual nature of MK14 as an inhibitor and detector of protein fibrillation makes it an attractive lead compound for monitoring and disrupting protein amyloidogenesis.
Genomic alterations in neuroendocrine prostate cancer: A systematic review and meta‐analysis
Authors: Chen Junru , Shi Mingchen , Chuen Choi Stephen Yiu , Wang Yu , Lin Dong , Zeng Hao , Wang Yuzhuo 
Published: January 2023

AbstractBackgroundNeuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer. We performed a systematic review and meta‐analysis to evaluate the prevalence of genomic alterations in NEPC and better understand its molecular features to potentially inform precision medicine.MethodsEMBASE, PubMed, and Cochrane Central Register of Controlled Trials databases were searched for eligible studies until March 2022. Study qualities were assessed using the Q‐genie tool. The prevalence of gene mutations and copy number alterations (CNAs) were extracted, and meta‐analysis was performed using R Studio with meta package.ResultsA total of 14 studies with 449 NEPC patients were included in this meta‐analysis. The most frequently mutated gene in NEPC was TP53 (49.8%), and the prevalence of deleterious mutations in ATM/BRCA was 16.8%. Common CNAs in NEPC included RB1 loss (58.3%), TP53 loss (42.8%), PTEN loss (37.0%), AURKA amplification (28.2%), and MYCN amplification (22.9%). RB1/TP53 alterations and concurrent RB1 and TP53 alterations were remarkably common in NEPC, with a prevalence of 83.8% and 43.9%, respectively. Comparative analyses indicated that the prevalence of (concurrent) RB1/TP53 alterations was significantly higher in de novo NEPC than in treatment‐emergent NEPC (t‐NEPC).ConclusionsThis study presents the comprehensive prevalence of common genomic alterations and potentially actionable targets in NEPC and reveals the genomic differences between de novo NEPC and t‐NEPC. Our findings highlight the importance of genomic testing in patients for precision medicine and provide insights into future studies exploring different NEPC subtypes.
The relationship between maternal periconceptional micronutrient supplementation and non‐syndromic cleft lip/palate in offspring
Authors: Liu Chunyi , Wang Di , Jin Lei , Zhang Jie , Meng Wenying , Jin Lei , Shang Xuejun 
Published: January 2023

AbstractBackgroundThis study aimed to explore the relationship between maternal periconceptional supplementation with folic acid only (FAO) or with multiple micronutrients containing folic acid (MMFA) and non‐syndromic cleft lip/palate in offspring.MethodThe data came from a prenatal health care system and a birth defects surveillance system in Beijing, China, from 2013 to 2018. Information on maternal FAO/MMFA supplementation was collected by questionnaire in the first trimester, and data on cleft lip/palate were collected at delivery or termination of pregnancy. Inverse probability weighting (IPW) by the propensity score to adjust for the confounders and Poisson regression model was used to estimate risk ratios (RRs) and their 95% confidence intervals (CIs).ResultsA total of 63,969 participants were included in the study. Compared to the no‐supplementation group, the adjusted RR for the supplementation group was 0.51 (95% CI: 0.40, 0.64). And the adjusted RRs for FAO and MMFA compared to the no‐supplementation group were 0.56 (95% CI: 0.40, 0.76) and 0.48 (95% CI: 0.35, 0.65), respectively. Compared to supplement FAO and MMFA with less than 8 days out of 10 days, the adjusted RRs for FAO and MMFA with 8 or more days out of 10 days were 1.17 (95% CI: 0.78, 1.75), and 2.05 (95% CI: 1.37, 3.31), respectively.ConclusionMaternal supplementation with micronutrients, either FAO or MMFA, during the periconceptional period can reduce the risk for non‐syndromic cleft lip/palate in offspring. However, women should be more cautious with MMFA supplementation.
Interdisciplinary training on instructional design using robots and IoT objects: A case study on undergraduates from different disciplines
Authors: Lin Vivien , Chen Nian‐Shing 
Published: January 2023

AbstractThe rise of robotics and the internet of things (IoT) has led to more interdisciplinary computing opportunities. With the real‐life application of these new technological affordances across disciplines, more universities are engaging students in practical, hands‐on interdisciplinary design. This case study aims to train two undergraduates from different disciplines to apply robots and IoT in instructional design to benefit young language learners. The two undergraduates, one majoring in engineering and the other majoring in applied foreign languages, voluntarily participated in this interdisciplinary project‐based learning (iPjBL). By creating an emulated environment that connects educational robots and tangible objects, the two designers achieved a theme‐based instructional game design. The researchers assessed the quality of their instructional design, compared their design processes, and identified three factors that led to differing designer perspectives—(a) disciplinary training, (b) prior experience, and (c) design beliefs. These different perspectives can be used to help design training for instructional designers from various disciplines on how to apply robots and IoT‐based tangible objects in language education. Challenges faced by the two designers included insufficient cross‐disciplinary expertise, existing knowledge and skill gaps, and the need to redefine design beliefs to achieve better design outcomes. Issues and needs related to interdisciplinary learning were addressed and synthesized into essential steps to guide future instructional design that incorporates robots and IoT‐based tangible objects. Overall evaluation of the interdisciplinary learning outcome using the First Principles of Instruction model demonstrated that iPjBL can provide valuable learning for instructional designers from different disciplines.
Destruction of a Copper Metal–Organic Framework to Induce CuPt Growth as a Heterojunction Catalyst for Hydrogen Peroxide Sensing
Authors: Jiang Lipei , Zhu Jiannan , Li Guangfang , Rao Zhuang , Wang Zhengyun , Liu Hongfang 
Published: January 2023

AbstractAssembling bimetallic alloys (BAs) with metal–organic frameworks (MOFs) to form heterojunctions has emerged as a promising strategy for the construction of highly active electrocatalysts. However, the current approaches to prepare BA@MOF heterojunctions suffer from poor controllability. In this work, a fascinating method involving partial thermal reduction and galvanic replacement to induce CuPt growth on a CuHHTP MOF (HHTP=2,3,6,7,10,11‐hexahydroxytriphenylene) is reported in order to construct a CuPt@CuHHTP heterojunction. The size of the CuPt nanoparticles can be effectively regulated by modifying the reduction temperature. The resultant CuPt NP@CuHHTP heterojunction nanoarrays exhibit high electrocatalytic activity and potential as an electrochemical H2O2 sensor with a low detection limit (5 nM), high sensitivity (6.942 mA ⋅ mM−1 ⋅ cm−2), and outstanding selectivity. This in situ approach provides not only new insights into the preparation of BA@MOF‐based heterojunctions but also an effective approach for the optimization of the catalytic performance of MOFs and related materials.
How to Decarbonize Our Energy Systems: Process‐Informed Design of New Materials for Carbon Capture
Authors: Garcia Susana , Smit Berend 
Published: January 2023

AbstractDecarbonisation from a variety of industrial and power emission sectors highlights a marked need for capture technologies that can be optimized for different CO2 sources and integrated into an equally diverse range of applications of captured CO2 as a feedstock. Some capture technologies are already operated at an industrial scale but may not be optimal for all required applications. Advanced tailored sorbent‐based technologies allow flexible operation and reduced costs as they offer higher capture capacities and significantly lower energy penalties than the state‐of‐the‐art systems. To accelerate the discovery, development, and deployment of novel advanced materials, it is critically important that efforts between experimentalists, theoreticians, and process engineers are coordinated. The PrISMa project addresses this challenge by integrating materials design with process design and environmental considerations to allow for tailor‐making carbon capture solutions optimally tuned for local sources and sinks. In this article, we highlight some of the recent results obtained with the PrISMa platform.
Radical Decarboxylative Cyanomethylation of Aliphatic Carboxylic Acids and Uronic Acids via Vinyl Azide Cascade Fragmentation
Authors: Xu Linhua , Li Qishuai , Li Dongwei , Zhou Xin , Song Ni , Wang Peng , Li Ming 
Published: January 2023

Comprehensive SummaryA direct oxidative radical decarboxylative cyanomethylation of carboxylic acids is described using 3‐azido‐2‐methylbut‐3‐en‐2‐ol as the carbon‐centered radical acceptor. The transformation is applicable to structurally diverse α‐amino acids, α‐oxy acids, α‐keto acids, pentofuranuronic acids, and hexopyranuronic acids. The mechanistic investigations suggest that a radical process is involved in the transformation. This work provides a potential approach to β‐amino acid, 5‐deoxy‐hexofuranose, and 6‐deoxy‐heptose constructs of biological relevance.
Design of all pass make over based capricious digital filter using eminent speed dual carry select adder and truncation and rounding approximate multiplier for image processing application
Authors: Mahendran P. , Kavitha M. S. , Radhika R. , Kotteeswaran C. 
Published: January 2023

SummaryA design of all pass make over based capricious digital filter using eminent speed dual carry select adder and truncation based scalable rounding approximate multiplier (APM‐CDF‐ESDCSA‐TOSAM) is proposed in this article for image processing application. The proposed ESDCSA‐TOSAM is used to speed up the filter design with less area and less power consumption. In the existing designs, a carry select adder was used that was a rapid binary adders, even though, it consumes maximal area and power. For that reason, lower power, area efficient with higher speed eminent speed dual carry select adder (ESDCSA) is used in this work. The proposed ESDCSA is a fastest binary adder, which consumes less power and area. To design the ESDCSA, three blocks are used: half sum with carry generator (HSCG), final carry generator (FCG), final sum generator (FSG), these are reducing the power and area. TOSAM is used to reduce more partial products by truncating each input operands depending on its leading one‐bit position. The proposed filter is designed on Xilinx ISE 14.5 design tools. The experimental performance of the proposed filter attains lower delay 59.61%, 37.91%, 34.99%, 28.09%, 44.04% and 38.23% compared with existing filters.