bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Selective Transport Route from Golgi to Late Endosomes That Requires the Yeast Gga Proteins
Authors: Black Michael W. , Pelham Hugh R.B. 
Published: July 2002

Pep12p is a yeast syntaxin located primarily in late endosomes. Using mutagenesis of a green fluorescent protein chimera we have identified a sorting signal FSDSPEF, which is required for transport of Pep12p from the exocytic pathway to late endosomes, from which it can, when overexpressed, reach the vacuole. When this signal is mutated, Pep12p instead passes to early endosomes, a step that is determined by its transmembrane domain. Surprisingly, Pep12p is then specifically retained in early endosomes and does not go on to late endosomes.
By testing appropriate chimeras in mutant strains, we found that FSDSPEF-dependent sorting was abolished in strains lacking Gga1p and Gga2p, Golgi-associated coat proteins with homology to gamma adaptin. In the gga1 gga2 double mutant endogenous Pep12p cofractionated with the early endosome marker Tlg1p, and recycling of Snc1p through early endosomes was defective. Pep12p sorting was also defective in cells lacking the clathrin heavy or light chain. We suggest that specific and direct delivery of proteins to early and late endosomes is required to maintain the functional heterogeneity of the endocytic pathway and that the GGA proteins, probably in association with clathrin, help create vesicles destined for late endosomes.
Removing redundancy in SWISS-PROT and TrEMBL.
Authors: O'Donovan C , Martin M J , Glemet E , Codani J J , Apweiler R 
Published: July 2002

Abstract
SUMMARY: One of the distinguishing criteria of the SWISS-PROT protein sequence data bank is minimal redundancy. The introduction of TrEMBL as a supplementary database ensured the comprehensiveness of SWISS-PROT and TrEMBL but introduced some degree of redundancy. We developed a strategy to identify the redundancy present within and between SWISS-PROT and TrEMBL and its subsequent removal. AVAILABILITY: The tools mentioned in this paper are available on request.
Making sense of microarray data distributions
Authors: Hoyle David C. , Rattray Magnus , Jupp Ray , Brass Andrew 
Published: July 2002

Abstract
Motivation: Typical analysis of microarray data has focusedon spot by spot comparisons within a single organism. Less analysis has been done on the comparison of the entire distribution of spot intensities between experiments and between organisms.
Results: Here we show that mRNA transcription data from a wide range of organisms and measured with a range of experimental platforms show close agreement with Benford’s law (Benford, Proc. Am. Phil. Soc. , 78, 551–572, 1938) and Zipf’s law (Zipf, The Psycho-biology of Language: an Introduction to Dynamic Philology , 1936 and Human Behaviour and the Principle of Least Effort , 1949). The distribution of the bulk of microarray spot intensities is well approximated by a log-normal with the tail of the distribution being closer to power law. The variance, σ2, of log spot intensity shows a positive correlation with genome size (in terms of number of genes) and is therefore relatively fixed within some range for a given organism. The measured value of σ2 can be significantly smaller than the expected value if the mRNA is extracted from a sample of mixed cell types. Our research demonstrates that useful biological findings may result from analyzing microarray data at the level of entire intensity distributions.
Contact: david.c.hoyle@man.ac.uk
* To whom correspondence should be addressed.
Validation of the ONKOTEV Risk Prediction Model for Venous Thromboembolism in Outpatients With Cancer
Authors: Cella Chiara A. , Knoedler Maren , Hall Marcia , Arcopinto Michele , Bagnardi Vincenzo , Gervaso Lorenzo , Pellicori Stefania , Spada Francesca , Zampino Maria G. , Ravenda Paola S. , Frassoni Samuele , Passaro Antonio , Milano Monica , Laffi Alice , Fazio Nicola , Lordick Florian 
Published: February 2023

ImportanceThe assessment of the risk of venous thromboembolism (VTE) among outpatients with cancer represents an unsolved topic. Current international guidelines recommend primary prophylaxis for patients at intermediate to high risk of VTE, indicated by a Khorana score of 2 or more. A previous prospective study developed the ONKOTEV score, a 4-variable risk assessment model (RAM) consisting of a Khorana score of more than 2, metastatic disease, vascular or lymphatic compression, and previous VTE event.ObjectiveTo validate the ONKOTEV score as a novel RAM to assess the risk of VTE among outpatients with cancer.Design, Setting, and ParticipantsONKOTEV-2 is a noninterventional prognostic study conducted in 3 European centers located in Italy, Germany, and the United Kingdom among a prospective cohort of 425 ambulatory patients with a histologically confirmed diagnosis of a solid tumor who were receiving active treatments. The total study duration was 52 months, with an accrual period of 28 months (from May 1, 2015, to September 30, 2017) and an overall follow up-period of 24 months (data were censored September 30, 2019). Statistical analysis was performed in October 2019.ExposuresThe ONKOTEV score was calculated for each patient at baseline by collecting clinical, laboratory, and imaging data from tests performed for routine practice. Each patient was then observed to detect any thromboembolic event throughout the study period.Main Outcomes and MeasuresThe primary outcome of the study was the incidence of VTE, including deep vein thrombosis and pulmonary embolism.ResultsA total of 425 patients (242 women [56.9%]; median age, 61 years [range, 20-92 years]) were included in the validation cohort of the study. The cumulative incidences for the risk of developing VTE at 6 months were 2.6% (95% CI, 0.7%-6.9%), 9.1% (95% CI, 5.8%-13.2%), 32.3% (95% CI, 21.0%-44.1%), and 19.3% (95% CI, 2.5%-48.0%), respectively, among 425 patients with an ONKOTEV score of 0, 1, 2, and greater than 2 (P &amp;lt; .001). The time-dependent area under the curve at 3, 6, and 12 months was 70.1% (95% CI, 62.1%-78.7%), 72.9% (95% CI, 65.6%-79.1%), and 72.2% (95% CI, 65.2%-77.3%), respectively.Conclusions and RelevanceThis study suggests that, because the ONKOTEV score has been validated in this independent study population as a novel predictive RAM for cancer-associated thrombosis, it can be adopted into practice and into clinical interventional trials as a decision-making tool for primary prophylaxis.
Association of Human Papillomavirus Status With Suicide Risk Among Patients With Head and Neck Cancer
Authors: Chakoma Tatenda , Moon Peter K. , Osazuwa-Peters Oyomoare L. , Megwalu Uchechukwu C. , Osazuwa-Peters Nosayaba 
Published: February 2023

ImportanceHuman papillomavirus (HPV) is strongly associated with head and neck cancer, and HPV status is considered a prognostic factor. Being a sexually transmitted infection, HPV-related cancers may have greater risk of stigma and psychological distress; however, the potential association of HPV-positive status with psychosocial outcomes, such as suicide, is understudied in head and neck cancer.ObjectiveTo investigate the association between HPV tumor status and suicide risk among patients with head and neck cancer.Design, Setting, and ParticipantsThis population-based retrospective cohort study included adult patients with clinically confirmed cases of head and neck cancer based on HPV tumor status from the Surveillance, Epidemiology, and End Results database from January 1, 2000, to December 31, 2018. Data analysis was conducted from February 1 to July 22, 2022.Main Outcomes and MeasuresThe outcome of interest was death by suicide. Primary measure was HPV status of tumor site, dichotomized as positive or negative. Covariates included age, race, ethnicity, marital status, cancer stage at presentation, treatment modality, and type of residence. Cumulative risk of suicide among patients with HPV-positive and HPV-negative head and neck cancer was assessed using Fine and Gray competing risk models.ResultsOf 60 361 participants, the mean (SD) age was 61.2 (13.65) years, and 17 036 (28.2%) were women; there were 347 (0.6%) American Indian, 4369 (7.2%) Asian, 5226 (8.7%) Black, 414 (0.7%) Native Hawaiian or Other Pacific Islander, and 49 187 (81.5%) White individuals. A competing risk analysis showed a significant difference in the cumulative incidence of suicide between HPV-positive cancers (5-year suicide-specific mortality, 0.43%; 95% CI, 0.33%-0.55%) and HPV-negative cancers (5-year suicide-specific mortality, 0.24%; 95% CI, 0.19%-0.29%). Tumor status that was HPV positive was associated with increased suicide risk in the unadjusted model (hazard ratio [HR], 1.76; 95% CI, 1.28-2.40), but not the fully adjusted model (adjusted HR, 1.18; 95% CI, 0.79-1.79). Among people with oropharyngeal cancer only, HPV status was associated with increased suicide risk, but the width of the confidence interval prevented definitive conclusion (adjusted HR, 1.61; 95% CI 0.88-2.94).Conclusions and RelevanceThe results of this cohort study suggest that patients with HPV-positive head and neck cancer have similar risk of suicide as patients with HPV-negative cancer, despite differences in overall prognosis. Early mental health interventions may be associated with reduced suicide risk in all patients with head and neck cancer and should be assessed in future work.
MicroRNA signature and integrative omics analyses define prognostic clusters and key pathways driving prognosis in patients with neuroendocrine neoplasms
Authors: Soldevilla Beatriz , Lens‐Pardo Alberto , Espinosa‐Olarte Paula , Carretero‐Puche Carlos , Molina‐Pinelo Sonia , Robles Carlos , Benavent Marta , Gomez‐Izquierdo Lourdes , Fierro‐Fernández Marta , Morales‐Burgo Patricia , Jimenez‐Fonseca Paula , Anton‐Pascual Beatriz , Rodriguez‐Gil Yolanda , Teijo‐Quintans Ana , La Salvia Anna , Rubio‐Cuesta Beatriz , Riesco‐Martínez Maria C. , Garcia‐Carbonero Rocio 
Published: February 2023

Neuroendocrine neoplasms (NENs) are mutationally quiet (low number of mutations/Mb), and epigenetic mechanisms drive their development and progression. We aimed at comprehensively characterising the microRNA (miRNA) profile of NENs, and exploring downstream targets and their epigenetic modulation. In total, 84 cancer‐related miRNAs were analysed in 85 NEN samples from lung and gastroenteropancreatic (GEP) origin, and their prognostic value was evaluated by univariate and multivariate models. Transcriptomics (N = 63) and methylomics (N = 30) were performed to predict miRNA target genes, signalling pathways and regulatory CpG sites. Findings were validated in The Cancer Genome Atlas cohorts and in NEN cell lines. We identified a signature of eight miRNAs that stratified patients in three prognostic groups (5‐year survival of 80%, 66% and 36%). Expression of the eight‐miRNA gene signature correlated with 71 target genes involved in PI3K–Akt and TNFα–NF‐kB signalling. Of these, 28 were associated with survival and validated in silico and in vitro. Finally, we identified five CpG sites involved in the epigenetic regulation of these eight miRNAs. In brief, we identified an 8‐miRNA signature able to predict survival of patients with GEP and lung NENs, and identified genes and regulatory mechanisms driving prognosis in NEN patients.
Analysis of CyberKnife intracranial treatment plans using ICRU 91 dose reporting: A retrospective study
Authors: Conlon Dion , Connolly James , Galal Mohamed , Ahmed Ismail , Foley Mark , Kleefeld Christoph 
Published: February 2023

AbstractICRU 91, published in 2017, is an international standard for prescribing, recording, and reporting stereotactic treatments. Since its release, there has been limited research published on the implementation and impact of ICRU 91 on clinical practice. This work provides an assessment of the recommended ICRU 91 dose reporting metrics for their use in clinical treatment planning. A set of 180 intracranial stereotactic treatment plans for patients treated by the CyberKnife (CK) system were analyzed retrospectively using the ICRU 91 reporting metrics. The 180 plans comprised 60 trigeminal neuralgia (TGN), 60 meningioma (MEN), and 60 acoustic neuroma (AN) cases. The reporting metrics included the planning target volume (PTV) near‐minimum dose (), near‐maximum dose (), and median dose (), as well as the gradient index (GI) and conformity index (CI). The metrics were assessed for statistical correlation with several treatment plan parameters. In the TGN plan group, owing to the small targets, was greater than in 42 plans, whereas both metrics were not applicable in 17 plans. The metric was predominantly influenced by the prescription isodose line (PIDL). The GI was significantly dependent on target volume in all analyses performed, where the variables were inversely related. The CI was only dependent on target volume in treatment plans for small targets. The ICRU 91 and metrics breakdown in plans for small target volumes below 1 cm3; the Min and Max pixel should be reported in such cases. The metric is of limited use for treatment planning. Given their volume dependence, the GI and CI metrics could potentially serve as plan evaluation tools in the planning of the sites analyzed in this study, which would ultimately improve treatment plan quality.
KCNA1 gain‐of‐function epileptic encephalopathy treated with 4‐aminopyridine
Authors: Müller Peter , Takacs Danielle S. , Hedrich Ulrike B. S. , Coorg Rohini , Masters Laura , Glinton Kevin E. , Dai Hongzheng , Cokley Jon A. , Riviello James J. , Lerche Holger , Cooper Edward C. 
Published: February 2023

AbstractPrecision medicine for Mendelian epilepsy is rapidly developing. We describe an early infant with severely pharmacoresistant multifocal epilepsy. Exome sequencing revealed the de novo variant p.(Leu296Phe) in the gene KCNA1, encoding the voltage‐gated K+ channel subunit KV1.1. So far, loss‐of‐function variants in KCNA1 have been associated with episodic ataxia type 1 or epilepsy. Functional studies of the mutated subunit in oocytes revealed a gain‐of‐function caused by a hyperpolarizing shift of voltage dependence. Leu296Phe channels are sensitive to block by 4‐aminopyridine. Clinical use of 4‐aminopyridine was associated with reduced seizure burden, enabled simplification of co‐medication and prevented rehospitalization.
Regulation of Chirality Transfer and Amplification from Chiral Cysteine to Gold Nanorod Assemblies using Nonchiral Surface Ligands
Authors: Zhang Chenqi , Gao Xinshuang , Li Hanbo , Ji Yinglu , Cai Rui , Hu Zhijian , Wu Xiaochun 
Published: February 2023

AbstractOwing to large chiroptical activity and high tunability, dynamic chiral superstructures of plasmonic nanoparticles have attracted great attention. A useful strategy has been developed to obtain strong plasmonic chiroptical responses (plasmonic circular dichroism, PCD) by adding small chiral thiols on achiral side‐by‐side assemblies of gold nanorods (AuNRs). Despite the critical role of chiral thiols, the impact of achiral surface ligands is yet to be revealed. Herein, the effects of achiral surface ligands are systematically investigated from the viewpoints of counter ion, hydrocarbon chain length, and head group of surfactants. A well‐packed ligand shell is found to be beneficial for the chirality transfer and amplification from adsorbed chiral thiols to rod assemblies. The PCD temperature amplification effect is observed by using different surfactant ligands and reflects the energy cost of rod‐twisting in the assemblies. This study deepens the understanding of chiral plasmonic assemblies driven by small chiral molecules and provides rational design to fabricate such assembly structures.
A Senomorphic‐Conjugated Scaffold for Application of Senescent Cells in Regenerative Medicine
Authors: Deng Wenqi , Jo Jun‐ichiro , Tanaka Tomonari , Morikuni Hidetoshi , Hashimoto Yoshiya , Matsumoto Naoyuki , Honda Yoshitomo 
Published: February 2023

AbstractProcuring a sufficient amount of cells is essential for cell‐based regenerative therapy. However, the application of senescent cells replicated using cell culture is limited because the cells have lost their regenerative ability or produce deleterious senescence‐associated secretory phenotypes (SASPs). In this study, using a senomorphic (epigallocatechin gallate [EGCG]), which could modulate SASP secretion from senescent cells, nonsenescent and senescent dedifferentiated fat cells from rats (rDFAT cells), and congenital cleft‐jaw defects in rats, the authors show that the senomorphic (EGCG)‐conjugated cellular scaffold restores the bone regenerative ability of senescent multipotent progenitor cells, even in vivo. In this osteogenic process, the EGCG‐conjugated scaffold attenuates the production of representative SASPs (i.e., interleukin [IL]‐6 and tumor necrosis factor‐α) and reactive oxygen species in vivo and in vitro. In polymerase chain reaction arrays in vitro, the EGCG‐conjugated cellular scaffold suppresses the expression of genes associated with deleterious SASP factors for bone formation (e.g., Csf2, IL‐1a, and others) from senescent rDFAT cells and elevates the expression of potential osteogenesis‐ and bone remodeling‐ related gene (e.g., Cxcl13 and Spp1). These results provide insights to expand the application of senomorphics and senescent stem/multipotent progenitor cells in cell‐based regenerative medicine.
Pixelating Responsive Structural Color via a Bioinspired Morphable Concavity Array (MoCA) Composed of 2D Photonic Crystal Elastomer Actuators
Authors: Pan Yi , Li Chang , Hou Xiaoyu , Yang Zhenyu , Li Mingzhu , Shum Ho Cheung 
Published: February 2023

AbstractStimuli‐responsive structural coloration allows the color change of soft substrates in response to environmental stimuli such as heat, humidity, and solvents. Such color‐changing systems enable smart soft devices, such as the camouflageable skin of soft robots or chromatic sensors in wearable devices. However, individually and independently programmable stimuli‐responsive color pixels remain significant challenges among the existing color‐changing soft materials and devices, which are crucial for dynamic display. Inspired by the dual‐color concavities on butterfly wings, a morphable concavity array to pixelate the structural color of two‐dimensional photonic crystal elastomer and achieve individually and independently addressable stimuli‐responsive color pixels is designed. The morphable concavity can convert its surface between concave and flat upon changes in the solvent and temperature, accompanied by angle‐dependent color‐shifting. Through multichannel microfluidics, the color of each concavity can be controllably switched. Based on the system, the dynamic display by forming reversibly editable letters and patterns for anti‐counterfeiting and encryption are demonstrated. It is believed that the strategy of pixelating optical properties through locally altering surface topography can inspire the design of new transformable optical devices, such as artificial compound eyes or crystalline lenses for biomimetic and robotic applications.
Design of Flame‐Made ZnZrOx Catalysts for Sustainable Methanol Synthesis from CO2
Authors: Pinheiro Araújo Thaylan , Morales‐Vidal Jordi , Zou Tangsheng , Agrachev Mikhail , Verstraeten Simon , Willi Patrik O. , Grass Robert N. , Jeschke Gunnar , Mitchell Sharon , López Núria , Pérez‐Ramírez Javier 
Published: February 2023

AbstractMixed zinc‐zirconium oxides, ZnZrOx, are highly selective and stable catalysts for CO2 hydrogenation to methanol, a pivotal energy vector. However, their activity remains moderate, and descriptors to design improved systems are lacking. This work applies flame spray pyrolysis (FSP), a one‐step and scalable method, to synthesize a series of ZnZrOx catalysts, and systematically compares them to coprecipitated (CP) analogs to establish deeper synthesis–structure–performance relationships. FSP systems (up to 5 mol%) generally display a threefold higher methanol productivity compared to their CP counterparts. In‐depth characterization and theoretical simulations show that, unlike CP, FSP maximizes the surface area and formation of atomically dispersed Zn2+ sites incorporated in lattice positions within the ZrO2 surface, which is key to improving performance. Analysis by in situ electron paramagnetic resonance (EPR) spectroscopy reveals that the specific architecture of the flame‐made catalyst markedly fosters the generation of oxygen vacancies. Together with surrounding Zn and Zr‐O atoms, the oxygen vacancies create active ensembles that favor methanol formation through the formate path while suppressing undesired CO production, as confirmed by kinetic modeling. This study elucidates the nature of active sites and their working mechanism, pushing forward ZnZrOx‐catalyzed methanol synthesis by providing a new benchmark for this cost‐effective and earth‐abundant catalyst family.
The clinical impact of COVID‐19 on endoscopic surgery in Japan: Analysis of data from the National Clinical Database
Authors: Shiroshita Hidefumi , Endo Hideki , Inomata Masafumi , Akagi Tomonori , Yamamoto Hiroyuki , Yamaguchi Shigeki , Eguchi Susumu , Wada Norihito , Kurokawa Yukinori , Seki Yosuke , Sakai Yoshiharu , Miyata Hiroaki , Kakeji Yoshihiro , Kitagawa Yuko , Taketomi Akinobu , Mori Masaki 
Published: February 2023

AbstractAimThis study aimed to evaluate the impact of the coronavirus disease (COVID‐19) pandemic on elective endoscopic surgeries in Japan using the National Clinical Database.MethodsWe retrospectively analyzed the clinicopathological factors and surgical outcomes of laparoscopic cholecystectomy (LC), laparoscopic distal gastrectomy (LDG), and laparoscopic low anterior resection (LLAR) and compared the monthly numbers of each procedure performed in 2020 with those in 2018 and 2019. The degree of infection in prefectures was classified into low and high groups.ResultsIn 2020, the number of LCs (except for acute cholecystitis) was 76 079 (93.0% of that in 2019), the number of LDGs was 14 271 (85.9% of that in 2019), and the number of LLARs was 19 570 (88.1% of that in 2019). Although the number of robot‐assisted LDG and LLAR cases increased in 2020, the growth rate was mild compared with that in 2019. There was little difference in the number of cases in the degree of infection in the prefectures. The numbers of LC, LDG, and LLAR cases decreased from May to June and recovered gradually. In late 2020, the proportion of T4 and N2 cases of gastric cancer and the number of T4 cases of rectal cancer increased compared with those in 2019. There was little difference between the proportions of postoperative complications and mortality in the three procedures between 2019 and 2020.ConclusionThe number of endoscopic surgeries decreased in 2020 as a result of the COVID‐19 pandemic. However, the procedures were performed safely in Japan.
Cyclic extrusion synthesis of mesoporous carbon‐supported metal catalysts for selective hydrogenation
Authors: Xu Jialu , Hou Shengtai , Niu Qiang , Zhang Pengfei , Luo Zheng‐Hong 
Published: February 2023

AbstractThe mesoporous carbon‐supported metal catalysts are important materials in heterogeneous catalysis. From the standpoint of process intensification, the current synthesis methods still suffer from several issues, such as the excessive use of toxic solvents, the time‐consuming self‐assembly process, and the difficulty of continuous production. Herein, we report a solvent‐free and continuous route to synthesize mesoporous carbon‐supported metal catalysts. Interestingly, the use of cyclic extrusion could promote mixing, coordination, and assembly of catalyst precursors (tannin‐metal salts‐additives) by shearing and squeeze force. The as‐made mesoporous carbon‐supported nickel materials showed high surface areas (up to 512 m2 g−1), narrow pore size distribution (~10 nm), and good performance in the selective hydrogenation of nitrobenzene to aniline (Conv. >99%; Sel. >99%). In addition, the fluid property of catalyst precursors and the geometry of the twin‐screw extrusion channel were studied, and the essence of this cyclic extrusion process is also discussed.