bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tau: More than a microtubule‐binding protein in neurons
Authors: Alonso Alejandra del Carmen , El Idrissi Abdeslem , Candia Robert , Morozova Viktoriya , Kleiman Frida Esther 
Published: October 2023

AbstractTau protein was discovered as a microtubule‐associated protein nearly 50 years ago, and our understanding of tau has revolved around that role. Even with tau's rise to stardom as a central player in neurodegenerative disease, therapeutic efforts have largely been targeted toward cytoskeletal changes. While some studies hinted toward non‐cytoskeletal roles for tau, it is only fairly recently that these ideas have begun to receive considerable attention. Many new binding partners for tau have been identified, including DNA, RNA, RNA‐binding proteins, some receptors, and other tau molecules. The diversity of tau binding partners coupled with the discovery of tau other than axonal compartments such as nucleus, dendrites, and synapses have led to the proposal of novel functions for tau in roles such as nuclear stability, cell signaling, transcriptional processing, and protein synthesis. Tau self‐assembly in particular has made an impact, leading to the hypothesis that a prion‐like function of hyperphosphorylated tau is central to tauopathies. With tau emerging as a multifaceted protein that operates in many parts of the cell and with many molecular partners, the field of tau biology is primed for discoveries that can provide new perspectives on both the unique biochemistry of tau and the nature of devastating neurological diseases.
The discovery of tau protein
Authors: Kirschner Marc 
Published: October 2023

AbstractIn January of this year I received an unexpected request from George Bloom to contribute an historical perspective on “the discovery of tau protein,” an event that occurred roughly 50 years ago. My first thought was that it could not have been that long ago, as the memories of what was my first independent scientific discovery are still fresh in my mind today. But 50 years is half a century and, as I thought about the events, I realized how much the practice of science has changed.
Discovery of a Dual‐Target Inhibitor of CDK7 and HDAC1 That Induces Apoptosis and Inhibits Migration in Colorectal Cancer**
Authors: Chen Yao , Zhang Shuangqian , Li Zhijia , Yin Bo , Liu Yi , Zhang Lan 
Published: October 2023

AbstractAberrant expression or dysfunction of cyclin‐dependent kinase 7(CDK7) and histone deacetylase 1 (HDAC1) are associated with the occurrence and progression of various cancers. In this study, we developed a series of dual‐target inhibitors by designing and synthesizing compounds that incorporate the pharmacophores of THZ2 and SAHA. The most potent dual‐target inhibitor displayed robust inhibitory activity against several types of cancer cells and demonstrated promising inhibitory effects on both CDK7 and HDAC1. After further mechanistic studies, it was discovered that this inhibitor effectively arrested HCT‐116 cells at the G2 phase and induced apoptosis. Additionally, it also significantly hindered the migration of HCT‐116 cells and exhibited notable anti‐tumor effects. These findings offer strong support for the development of dual‐target inhibitors of CDK7 and HDAC1 and provide a promising avenue for future cancer therapy.
Moving out of CF3‐Land: Synthesis, Receptor Affinity, and in silico Studies of NK1 Receptor Ligands Containing a Pentafluorosulfanyl (SF5) Group
Authors: Witoszka Katarzyna , Matalińska Joanna , Misicka Aleksandra , Lipiński Piotr F. J. 
Published: October 2023

AbstractThe NK1 receptor (NK1R) is a molecular target for both approved and experimental drugs intended for a variety of conditions, including emesis, pain, and cancers. While contemplating modifications to the typical NK1R pharmacophore, we wondered whether the CF3 groups common for many NK1R ligands, could be replaced with some other moiety. Our attention was drawn by the SF5 group, and so we designed, synthesized, and tested ten novel SF5‐containing compounds for NK1R affinity. All analogues exhibit detectable NK1R binding, with the best of them, compound 5 a, (3‐bromo‐5‐(pentafluoro‐λ6‐sulfanyl)benzyl acetyl‐L‐tryptophanate) binding only slightly worse (IC50=34.3 nM) than the approved NK1R‐targeting drug, aprepitant (IC50=27.7 nM). Molecular docking provided structural explanation of SAR. According to our analysis, the SF5 group in our compounds occupies a position similar to that of one of the CF3 groups of aprepitant as found in the crystal structure. Additionally, we checked whether the docking scoring function or energies derived from Fragment Molecular Orbital quantum chemical calculations may be helpful in explaining and predicting the experimental receptor affinities for our analogues. Both these methods produce moderately good results. Overall, this is the first demonstration of the utility of the SF5 group in the design of NK1R ligands.
A surrogate molecular approach for the detection of Philadelphia chromosome–like B‐acute lymphoblastic leukemia
Authors: Gupta Dikshat Gopal , Varma Neelam , Abdulkadir Sarki Abba , Sreedharanunni Sreejesh , Sachdeva Man Updesh Singh , Naseem Shano , Bose Parveen , Binota Jogeshwar , Malhotra Pankaj , Khadwal Alka , Trehan Amita , Varma Subhash 
Published: October 2023

AbstractBackgroundPhiladelphia chromosome (Ph)–like B‐acute lymphoblastic leukemia (B‐ALL) is a clinically significant, high‐risk genetic subtype of B‐ALL cases. There are few data on the incidence, characterization, and treatment outcomes of Ph‐like ALL cases from low‐ and middle‐income countries. There is a pressing need to establish a well‐organized/cost‐effective approach for identifying Ph‐like ALL instances.MethodsMultiplex reverse transcriptase polymerase chain reaction, nCounter NanoString, and fluorescence in situ hybridization were used to detect and characterize Ph‐like ALL cases among recurrent genetic abnormalities (RGA)neg B‐ALL cases. At the end of induction therapy, flow cytometry‐minimal residual disease (MRD) assay was used to quantify MRD positivity in Ph‐like ALL cases.ResultsOf 130 newly diagnosed B‐ALL cases, 25% (BCR::ABL1), 4% (ETV6::RUNX1), 5% (TCF3::PBX1), 2% (KM2TA::AFF1), and 65% RGAneg B‐ALL cases were revealed by multiplex reverse transcriptase polymerase chain reaction. Among RGAneg B‐ALL cases, 24% Ph‐like ALL cases using nCounter NanoString were identified, with 48% CRLF2high cases with 45% CRLF2::P2RY8 and 18% CRLF2::IGH rearrangements(∼r) revealed by fluorescence in situ hybridization. In 52% of CRLF2low cases, 17% ABL1 and JAK2∼r 8% EPOR::IGH & PDGRFB∼r were identified. Ph‐like ALL cases had higher total leukocyte count (p < .05), male preponderance (p < .05), and high MRD‐positivity/induction failure compared with RGAneg B‐ALL cases. Furthermore, in Ph‐like ALL cases, 11 significant genes using quantitative polymerase chain reaction were identified and validated. CRLF2, IGJ, CEACAM6, MUC4, SPATS2L and NRXN3 genes were overexpressed and show statistical significance (p < .05) in Ph‐like ALL cases.ConclusionsThis study showed the high incidence of Ph‐like ALL cases with kinase activating alterations and treatment outcomes from low‐ and middle‐income region. Furthermore, a surrogate cost‐effective multiplex panel of 11 overexpressed genes for the prompt detection of Ph‐like ALL cases is proposed.Plain Language Summary

Identification of recurrent gene abnormalities (RGA)neg B‐acute lymphoblastic leukemia (B‐ALL) cases using multiplex‐reverse transcriptase polymerase chain reaction.
Identification and characterization of Philadelphia (Ph)–like ALL cases using nCounter NanoString gene expression profiling and fluorescence in situ hybridization.
Furthermore, Ph‐like ALL cases were characterized according to CRLF2 expression and kinase‐activating genomic alterations. Minimal residual disease of Ph‐like ALL cases were quantified using flow cytometry‐minimal residual disease assay.
A surrogate molecular approach was established to detect Ph‐like ALL cases from low‐ and middle‐income countries.
SMAD4 loss predicts worse overall and distant metastasis‐free survival in patients with resected pancreatic adenocarcinoma
Authors: Anstadt Emily J. , Carmona Ruben , Berlin Eva , Yegya‐Raman Nikhil , Venigalla Sriram , Reddy Vishruth , Williams Graeme R. , Leibensperger Mark R. , Wojcieszynski Andrzej , Baumann Brian C. , Lee Major K. , Plastaras John P. , Furth Emma E. , Mell Loren K. , Metz James M. , Ben‐Josef Edgar 
Published: October 2023

AbstractBackgroundIn select patients, pancreatic adenocarcinoma remains a local disease, yet there are no validated biomarkers to predict this behavior and who may benefit from aggressive local treatments. This study sought to determine if SMAD4 (mothers against decapentaplegic homolog 4) messenger RNA–sequencing (RNA‐seq) expression is a robust method for predicting overall survival (OS) and distant metastasis‐free survival (DMFS) in patients with resected pancreatic adenocarcinoma.MethodsUtilizing The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC), 322 patients with resected stage I–III pancreatic adenocarcinoma were identified. In TCGA, multivariable proportional hazards models were used to determine the association of SMAD4 genomic aberrations and RNA‐seq expression with OS and DMFS. In the ICGC, analysis sought to confirm the predictive performance of RNA‐seq via multivariable models and receiver operator characteristic curves.ResultsIn TCGA, the presence of SMAD4 genomic aberrations was associated with worse OS (hazard ratio [HR], 1.55; 95% CI, 1.00–2.40; p = .048) but not DMFS (HR, 1.33; 95% CI, .87–2.03; p = .19). Low SMAD4 RNA‐seq expression was associated with worse OS (HR, 1.83; 95% CI, 1.17–2.86; p = .008) and DMFS (HR, 1.70; 95% CI, 1.14–2.54; p = .009). In the ICGC, increased SMAD4 RNA‐seq expression correlated with improved OS (area under the curve [AUC], .92; 95% CI, .86–.94) and DMFS (AUC, .84; 95% CI, .82–.87).ConclusionsIn patients with resected pancreatic adenocarcinoma, SMAD4 genomic aberrations are associated with worse OS but do not predict for DMFS. Increased SMAD4 RNA‐seq expression is associated with improved OS and DMFS in patients with resected pancreatic adenocarcinoma. This reproducible finding suggests SMAD4 RNA‐seq expression may be a useful marker to predict metastatic spread.
Muscle channelopathies: A review
Authors: McGowan Bridget R. , Schwaede Abigail N. , De Simone Lenika , Rao Vamshi K. 
Published: October 2023

AbstractBackgroundMuscle channelopathies are a rare and heterogeneous group of disorders that can be clinically challenging and functionally disabling. These disorders can present in both adult and pediatric age groups. These disorders have been known since the turn of the 20th century, with a steady evolution in terms of understanding the pathophysiology, phenotype, diagnostic, and treatment modalities over the last three decades.MethodsWe present a comprehensive review of muscle channelopathies that includes nondystrophic myotonias and periodic paralyses. The disorders in this review have been classified based on the presence or absence of myotonia on either the clinical exam or on electrophysiological testing. The historical background, genetics, pathophysiology, phenotypic presentations, and treatment modalities of each disorder reveal similarities as well as specific nuances in the disease phenotypes. Neurophysiologic testing shows differences in responses on routine and exercise testing and can narrow the differential within subsets of nondystrophic myotonias and periodic paralyses. The advances in genetics further aid in specifying which of the putative channels are at fault. Management can then be guided by knowledge of the causative gene and involves either avoidance of triggers or channel‐based therapeutics.ConclusionMuscle channelopathies are rare, but a high index of suspicion along with a knowledge of the phenotype will help guide neurophysiological and genetic testing. A muscle channelopathy diagnosis, subsequently, can assist in avoiding triggers and directing treatments.
Tracing task‐based runtime systems: Feedbacks from theStarPUcase
Authors: Denis Alexandre , Jeannot Emmanuel , Swartvagher Philippe , Thibault Samuel 
Published: October 2023

SummaryGiven the complexity of current supercomputers and applications, being able to trace application executions to understand their behavior is not a luxury. As constraints, tracing systems have to be as little intrusive as possible in the application code and performances, and be precise enough in the collected data. In this article, we present how works the tracing system used by the task‐based runtime systemStarPU. We study the different sources of performance overhead coming from the tracing system and how to reduce these overheads. Then, we evaluate the accuracy of distributed traces with different clock synchronization techniques. Finally, we summarize our experiments and conclusions with the lessons we learned to efficiently trace applications, and the list of characteristics each tracing system should feature to be competitive. The reported experiments and implementation details comprise a feedback of integrating into a task‐based runtime system state‐of‐the‐art techniques to efficiently and precisely trace application executions. We highlight the points every application developer or end‐user should be aware of to seamlessly integrate a tracing system or just trace application executions.
Object‐aware deep feature extraction for feature matching
Authors: Li Zuoyong , Wang Weice , Lai Taotao , Xu Haiping , Keikhosrokiani Pantea 
Published: October 2023

SummaryFeature extraction is a fundamental step in the feature matching task. A lot of studies are devoted to feature extraction. Recent researches propose to extract features by pre‐trained neural networks, and the output is used for feature matching. However, the quality and the quantity of the features extracted by these methods are difficult to meet the requirements for the practical applications. In this article, we propose a two‐stage object‐aware‐based feature matching method. Specifically, the proposed object‐aware block predicts a weighted feature map through a mask predictor and a prefeature extractor, so that the subsequent feature extractor pays more attention to the key regions by using the weighted feature map. In addition, we introduce a state‐of‐the‐art model estimation algorithm to align image pair as the input of the object‐aware block. Furthermore, our method also employs an advanced outlier removal algorithm to further improve matching quality. Experimental results show that our object‐aware‐based feature matching method improves the performance of feature matching compared with several state‐of‐the‐art methods.
Synthesis of Organic Optoelectronic Materials Using Direct C−H Functionalization
Authors: Kuwabara Junpei , Kanbara Takaki 
Published: October 2023

AbstractSmall molecules and polymers with conjugated structures can be used as organic optoelectronic materials. These molecules have conventionally been synthesized by cross‐coupling reactions; however, in recent years, direct functionalization of C−H bonds has been used to synthesize organic optoelectronic materials. Representative reactions include direct arylation reactions (C−H/C−X couplings, with X being halogen or pseudo‐halogen) and cross‐dehydrogenative coupling (C−H/C−H cross‐coupling) reactions. Although these reactions are convenient for short‐step synthesis, they require regioselectivity in the C−H bonds and suppression of undesired homo‐coupling side reactions. This review introduces examples of the synthesis of organic optoelectronic materials using two types of direct C−H functionalization reactions. In addition, we summarize our recent activities in the development of direct C−H functionalization reactions using fluorobenzenes as substrates. This review covers the reaction mechanism and material properties of the resulting products.
Hybrid simulation of the plasma characteristics in a dual‐frequency dual‐antenna inductively coupled plasma discharge
Authors: Sun Xiao‐Yan , Yang Ming‐Hui , Shao Wei‐Li , Tao Xin , Li Long‐Wei 
Published: October 2023

AbstractDual‐frequency (DF) dual‐antenna inductively coupled plasma (ICP) sources have been proposed as one of the methods to produce large‐area uniform plasma. In this study, a hybrid model, consisting of a fluid module and an electron Monte Carlo (eMC) module, is used to further investigate the modulation of the plasma characteristics (i.e., induced electric field, electron energy distribution, electron heating mechanism, electron temperature, and plasma density) by the low‐frequency (LF) and high‐frequency (HF) currents in a DF argon discharge. When the inner LF current increases from 12 to 22 A at a fixed outer HF current of 10 A, the induced electric field is strengthened near the LF coil and weakened near the HF coil. The fraction of high‐energy electrons at different spatial positions increases with the increase of LF current, which is caused by the sufficient collision heating in the skin layer of LF source, leading to an increase in electron temperature. When the outer HF current rises from 7 to 13 A with the inner LF current fixed at 17 A, the induced electric field is enhanced near the HF coil and weakened near the LF coil. The fraction of low‐energy electrons at different positions increases with the increase of HF current since the energetic electrons from the skin layer of HF source are cooled due to the ionization, excitation, and stepwise ionization collisions between electrons and neutral particles, as well as the weakened induced electric field near the LF coil. As a result, the electron temperature drops with the increase of HF current. Moreover, when the LF and HF currents increase, the plasma density increases, and the distribution of plasma density is also significantly modulated.
OMIP‐099: 31‐color spectral flow cytometry panel to investigate the steady‐state phenotype of human T cells
Authors: Zacharias Zeb R. , Houtman Jon C. D. 
Published: October 2023

AbstractWe have developed a 31‐color panel to define the steady‐state phenotype of T cells in human peripheral blood (Table 1). The panel presented here was optimized using cryopreserved peripheral blood mononuclear cells (PBMC). The markers included in this panel were chosen in order to characterize the steady‐state phenotype of T cells and includes markers (CD45RA, CD45RO, CCR7, CD95) to distinguish the main subsets (e.g., naïve, TEM, TCM, TEMRA, TSCM etc.) of CD4, CD8, and γδ T cells. This panel also includes markers for the identification of differentiation status (CD27, CD28), activation/antigen experience status (CD11a, CD49d, CD38, HLA‐DR, CD56, and CD39), co‐inhibitory marker expression (PD‐1, TIM‐3), and CD4 T helper subsets (CXCR3, CXCR5, CCR4, CCR6, Foxp3, CD25, and CD127). This optimized panel provides a broad assessment of the steady‐state phenotype of human T cells.
Timing‐deviation and frequency‐offset estimations for multicarrier transmission in high mobility environments using deep neural network
Authors: Wu Hong , Geng Xue , Chen Zhuo , Zhao Yingxin 
Published: October 2023

SummaryThe multicarrier technology used in fourth‐generation (4G) and fifth‐generation (5G) communications is quite susceptible to multipath fading and Doppler frequency shift, which is more prominent in high mobility environments. Therefore, the accuracy of timing and frequency synchronization impacts the overall system performance significantly. Existing synchronization methods rely on the correlation of the preamble sequences and are, hence, vulnerable to severe multipath effect and Doppler effect. In this article, we propose a novel scheme leveraging deep neural network (DNN) to achieve high‐precision synchronization in high mobility environments. Concretely, a convolutional neural network (CNN) architecture is proposed to extract the hidden features of received signals for timing deviation estimation. In the following, a fully connected (FC) model is demonstrated to classify the optimal carrier frequency offset (CFO) estimate from several CFO candidates. The proposed synchronization scheme is assessed under extended vehicular A (EVA) channel with various Doppler frequency shifts. Simulation results corroborate that the proposed DNN‐based scheme achieves a significant performance gain over the conventional correlation methods, and the proposed timing deviation estimation scheme exhibits an excellent complexity reduction; wherefore, it is extremely promising for multicarrier transmission systems in high mobility environments.
Colloid and pigmented histiocytes in lymph node aspirates as a clue to metastasis in patients with a history of papillary thyroid carcinoma
Authors: Ng Joanna K. M. , Chan Amy B. W. , Li Joshua J. X. 
Published: October 2023

AbstractIntroductionCystic changes, calcification, colloid material, and multinucleated giant cells are frequently associated with primary and metastatic papillary thyroid carcinoma (PTC). These features are sometimes present in negative lymph node fine‐needle aspiration cytology (FNAC). This study aims to review nodal aspirates of PTC to elucidate the significance of these cytological features in aspirates without tumor cells.MethodsFNAC specimens from patients with PTC confirmed on thyroidectomy were reviewed for cystic changes, tumor‐associated features, and lymphoid components. Histologic follow‐up of the lymph nodes were retrieved for correlation.ResultsA total of 113 aspirates were retrieved, of which 79 showed tumor cells on the FNAC specimen, and 95 were matched to a positive lymph node histology. At univariable analysis, calcification (n = 18/113, p = .044), colloid material (n = 40/113, p = .001), multinucleated giant cells (n = 29/113, p = .028), tumor cells (n = 79/133, p < .001), foamy histiocytes (n = 36/113, p = .002) and pigmented histiocytes (n = 62/113, p < .001) were associated with a positive histology. Presence of lymphoid fragments (n = 11/113, p < .001) and abundant background lymphocytes correlated with a negative histologic follow‐up (n = 45/113, p = .005). In aspirates without tumor cells, multivariable analysis demonstrated colloid material (p < .001) and pigmented histiocytes (p = .003) to be independently predictive of metastatic PTC, whereas lymphoid fragments (p < .001) were independently associated with a negative histologic follow up.ConclusionColloid material and pigmented histiocytes, and to lesser degree calcification and multinucleated giant cells, when seen in an aspirate without tumor cells, raises suspicion metastatic disease. On the contrary, the lymphoid fragments can be regarded as supportive evidence of adequate sampling and a true negative result.