bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase I study of an adenoviral vector delivering a MUC1/CD40-ligand fusion protein in patients with advanced adenocarcinoma
Authors: Tan Tira J. , Ang W. X. Gladys , Wang Who-Whong , Chong Hui-Shan , Tan Sze Huey , Cheong Rachael , Chia John Whay-Kuang , Syn Nicholas L. , Shuen Wai Ho , Ba Rebecca , Kaliaperumal Nivashini , Au Bijin , Hopkins Richard , Li Xinhua , Tan Aaron C. , Seet Amanda O. L. , Connolly John E. , Arkachaisri Thaschawee , Chew Valerie , Lajam Ahmad bin Mohamed , Guo Dianyan , Chew Marvin Z. W. , Wasser Martin , Kumar Pavanish , Albani Salvatore , Toh Han Chong 
Published: October 2022

AbstractCancer vaccines as immunotherapy for solid tumours are currently in development with promising results. We report a phase 1 study of Ad-sig-hMUC1/ecdCD40L (NCT02140996), an adenoviral-vector vaccine encoding the tumour-associated antigen MUC1 linked to CD40 ligand, in patients with advanced adenocarcinoma. The primary objective of this study is safety and tolerability. We also study the immunome in vaccinated patients as a secondary outcome. This trial, while not designed to determine clinical efficacy, reports an exploratory endpoint of overall response rate. The study meets its pre-specified primary endpoint demonstrating safety and tolerability in a cohort of 21 patients with advanced adenocarcinomas (breast, lung and ovary). The maximal dose of the vaccine is 1 ×1011viral particles, with no dose limiting toxicities. All drug related adverse events are of low grades, most commonly injection site reactions in 15 (71%) patients. Using exploratory high-dimensional analyses, we find both quantitative and relational changes in the cancer immunome after vaccination. Our data highlights the utility of high-dimensional analyses in understanding and predicting effective immunotherapy, underscoring the importance of immune competency in cancer prognosis.
Strain level microbial detection and quantification with applications to single cell metagenomics
Authors: Zhu Kaiyuan , Schäffer Alejandro A. , Robinson Welles , Xu Junyan , Ruppin Eytan , Ergun A. Funda , Ye Yuzhen , Sahinalp S. Cenk 
Published: October 2022

AbstractComputational identification and quantification of distinct microbes from high throughput sequencing data is crucial for our understanding of human health. Existing methods either use accurate but computationally expensive alignment-based approaches or less accurate but computationally fast alignment-free approaches, which often fail to correctly assign reads to genomes. Here we introduce CAMMiQ, a combinatorial optimization framework to identify and quantify distinct genomes (specified by a database) in a metagenomic dataset. As a key methodological innovation, CAMMiQ uses substrings of variable length and those that appear in two genomes in the database, as opposed to the commonly used fixed-length, unique substrings. These substrings allow to accurately decouple mixtures of highly similar genomes resulting in higher accuracy than the leading alternatives, without requiring additional computational resources, as demonstrated on commonly used benchmarking datasets. Importantly, we show that CAMMiQ can distinguish closely related bacterial strains in simulated metagenomic and real single-cell metatranscriptomic data.
Nutrient regulation of lipochitooligosaccharide recognition in plants via NSP1 and NSP2
Authors: Li Xin-Ran , Sun Jongho , Albinsky Doris , Zarrabian Darius , Hull Raphaella , Lee Tak , Jarratt-Barnham Edwin , Chiu Chai Hao , Jacobsen Amy , Soumpourou Eleni , Albanese Alessio , Kohlen Wouter , Luginbuehl Leonie H. , Guillotin Bruno , Lawrensen Tom , Lin Hui , Murray Jeremy , Wallington Emma , Harwood Wendy , Choi Jeongmin , Paszkowski Uta , Oldroyd Giles E. D. 
Published: October 2022

AbstractMany plants associate with arbuscular mycorrhizal fungi for nutrient acquisition, while legumes also associate with nitrogen-fixing rhizobial bacteria. Both associations rely on symbiosis signaling and here we show that cereals can perceive lipochitooligosaccharides (LCOs) for activation of symbiosis signaling, surprisingly including Nod factors produced by nitrogen-fixing bacteria. However, legumes show stringent perception of specifically decorated LCOs, that is absent in cereals. LCO perception in plants is activated by nutrient starvation, through transcriptional regulation of Nodulation Signaling Pathway (NSP)1 and NSP2. These transcription factors induce expression of an LCO receptor and act through the control of strigolactone biosynthesis and the karrikin-like receptor DWARF14-LIKE. We conclude that LCO production and perception is coordinately regulated by nutrient starvation to promote engagement with mycorrhizal fungi. Our work has implications for the use of both mycorrhizal and rhizobial associations for sustainable productivity in cereals.
Chemical space docking enables large-scale structure-based virtual screening to discover ROCK1 kinase inhibitors
Authors: Beroza Paul , Crawford James J. , Ganichkin Oleg , Gendelev Leo , Harris Seth F. , Klein Raphael , Miu Anh , Steinbacher Stefan , Klingler Franca-Maria , Lemmen Christian 
Published: October 2022

AbstractWith the ever-increasing number of synthesis-on-demand compounds for drug lead discovery, there is a great need for efficient search technologies. We present the successful application of a virtual screening method that combines two advances: (1) it avoids full library enumeration (2) products are evaluated by molecular docking, leveraging protein structural information. Crucially, these advances enable a structure-based technique that can efficiently explore libraries with billions of molecules and beyond. We apply this method to identify inhibitors of ROCK1 from almost one billion commercially available compounds. Out of 69 purchased compounds, 27 (39%) have Ki values < 10 µM. X-ray structures of two leads confirm their docked poses. This approach to docking scales roughly with the number of reagents that span a chemical space and is therefore multiple orders of magnitude faster than traditional docking.
Phonon downconversion to suppress correlated errors in superconducting qubits
Authors: Iaia V. , Ku J. , Ballard A. , Larson C. P. , Yelton E. , Liu C. H. , Patel S. , McDermott R. , Plourde B. L. T. 
Published: October 2022

AbstractQuantum error correction can preserve quantum information in the presence of local errors, but correlated errors are fatal. For superconducting qubits, high-energy particle impacts from background radioactivity produce energetic phonons that travel throughout the substrate and create excitations above the superconducting ground state, known as quasiparticles, which can poison all qubits on the chip. We use normal metal reservoirs on the chip back side to downconvert phonons to low energies where they can no longer poison qubits. We introduce a pump-probe scheme involving controlled injection of pair-breaking phonons into the qubit chips. We examine quasiparticle poisoning on chips with and without back-side metallization and demonstrate a reduction in the flux of pair-breaking phonons by over a factor of 20. We use a Ramsey interferometer scheme to simultaneously monitor quasiparticle parity on three qubits for each chip and observe a two-order of magnitude reduction in correlated poisoning due to background radiation.
Ethylene industrial emitters seen from space
Authors: Franco Bruno , Clarisse Lieven , Van Damme Martin , Hadji-Lazaro Juliette , Clerbaux Cathy , Coheur Pierre-François 
Published: October 2022

AbstractVolatile organic compounds are emitted abundantly from a variety of natural and anthropogenic sources. However, in excess, they can severely degrade air quality. Their fluxes are currently poorly represented in inventories due to a lack of constraints from global measurements. Here, we track from space over 300 worldwide hotspots of ethylene, the most abundant industrially produced organic compound. We identify specific emitters associated with petrochemical clusters, steel plants, coal-related industries, and megacities. Satellite-derived fluxes reveal that the ethylene emissions of the industrial sources are underestimated or missing in the state-of-the-art Emission Database for Global Atmospheric Research (EDGAR) inventory. This work exposes global emission point-sources of a short-lived carbonated gas, complementing the ongoing large-scale efforts on the monitoring of inorganic pollutants.
The immune synapses reveal aberrant functions of CD8 T cells during chronic HIV infection
Authors: Anikeeva Nadia , Steblyanko Maria , Kuri-Cervantes Leticia , Buggert Marcus , Betts Michael R. , Sykulev Yuri 
Published: October 2022

AbstractChronic HIV infection causes persistent low-grade inflammation that induces premature aging of the immune system including senescence of memory and effector CD8 T cells. To uncover the reasons of gradually diminished potency of CD8 T cells from people living with HIV, here we expose the T cells to planar lipid bilayers containing ligands for T-cell receptor and a T-cell integrins and analyze the cellular morphology, dynamics of synaptic interface formation and patterns of the cellular degranulation. We find a large fraction of phenotypically naive T cells from chronically infected people are capable to form mature synapse with focused degranulation, a signature of a differentiated T cells. Further, differentiation of aberrant naive T cells may lead to the development of anomalous effector T cells undermining their capacity to control HIV and other pathogens that could be contained otherwise.
Harvesting metadata in clinical care: a crosswalk between FHIR, OMOP, CDISC and openEHR metadata
Authors: Bönisch Caroline , Kesztyüs Dorothea , Kesztyüs Tibor 
Published: October 2022

AbstractMetadata describe information about data source, type of creation, structure, status and semantics and are prerequisite for preservation and reuse of medical data. To overcome the hurdle of disparate data sources and repositories with heterogeneous data formats a metadata crosswalk was initiated, based on existing standards. FAIR Principles were included, as well as data format specifications. The metadata crosswalk is the foundation of data provision between a Medical Data Integration Center (MeDIC) and researchers, providing a selection of metadata information for research design and requests. Based on the crosswalk, metadata items were prioritized and categorized to demonstrate that not one single predefined standard meets all requirements of a MeDIC and only a maximum data set of metadata is suitable for use. The development of a convergence format including the maximum data set is the anticipated solution for an automated transformation of metadata in a MeDIC.
Effect of oral magnesium supplement on cardiometabolic markers in people with prediabetes: a double blind randomized controlled clinical trial
Authors: Salehidoost Rezvan , Taghipour Boroujeni Golshan , Feizi Awat , Aminorroaya Ashraf , Amini Masoud 
Published: October 2022

AbstractTo evaluate the effect of magnesium supplementation on insulin resistance and cardiovascular markers in people with prediabetes. A 12 week double-blind placebo-controlled randomized clinical trial was conducted at Isfahan Endocrine and Metabolism Research Center, Iran, on people with prediabetes (n = 86) to compare the effects of magnesium oxide 250 mg/day versus a placebo on anthropometric indices, blood pressure, fasting glucose, insulin, HOMA-IR index, C-reactive protein, uric acid and lipid profile. Both groups had similar distributions of anthropometric and biochemical variables at baseline. Those who received magnesium supplementation had significantly higher levels of HDL-cholesterol compared to the placebo group at the end of the study (49.7 ± 10.9 vs 43.6 ± 7.2 mg/dL, P = 0.003). The mean changes of HOMA-IR index, total cholesterol, LDL-cholesterol, triglyceride, uric acid and C-reactive protein levels as well as anthropometric indices and blood pressure in supplemented and placebo groups did not differ significantly. Magnesium supplementation increased HDL-cholesterol levels in people with prediabetes. However, other cardiometabolic markers were not improved by magnesium supplementation at the above dosage and duration.
Proximal discrepancy in intrinsic atomic interaction arrests G2/M phase by inhibiting Cyclin B1/CDK1 to infer molecular and cellular biocompatibility of d-limonene
Authors: Mandal Deepa , Patel Paritosh , Verma Suresh K. , Sahu Bikash Ranjan , Parija Tithi 
Published: October 2022

AbstractThe quest for different natural compounds for different biomedical applications especially in the treatment of cancer is at a high pace with increasing incidence of severity.d-limonene has been portrayed as one of the effective potential candidate centered to the context of breast cancer. The anticipation of its count as an effective biomedical agent required a detailed understanding of their molecular mechanism of biocompatibility. This study elucidates the mechanistic action ofd-limonene channelized by the induction of apoptosis for controlling proliferation in breast cancer cells. The possible mechanism was explored through an experimental and computational approach to estimate cell proliferation inhibition, cell cycle phase distribution, apoptosis analysis using a flow cytometry, western blotting and molecular docking. The results showed reduced dose and time-dependent viability of MCF7 cells. The study suggested the arrest of the cell cycle at G2/M phase leading to apoptosis and other discrepancies of molecular activity mediated via significant alteration in protein expression pattern of anti-apoptotic proteins like Cyclin B1 and CDK1. Computational analysis showed firm interaction ofd-limonene with Cyclin B1 and CDK1 proteins influencing their structural and functional integrity indicating the mediation of mechanism. This study concluded thatd-limonene suppresses the proliferation of breast cancer cells by inducing G2/M phase arrest via deregulation of Cyclin B1/CDK1.
Differential analysis of microbiomes in mucus and tissues obtained from colorectal cancer patients
Authors: Tajima Yosuke , Okuda Shujiro , Hanai Tsunekazu , Hiro Junichiro , Masumori Koji , Koide Yoshikazu , Kamiya Tadahiro , Cheong Yeongcheol , Inaguma Gaku , Shimada Yoshifumi , Wakai Toshifumi , Takihara Hayato , Akimoto Shingo , Matsuoka Hiroshi , Uyama Ichiro , Suda Koichi 
Published: October 2022

AbstractThe outer mucus layer of the colorectal epithelium is easily removable and colonized by commensal microbiota, while the inner mucus layer is firmly attached to the epithelium and devoid of bacteria. Although the specific bacteria penetrating the inner mucus layer can contact epithelial cells and trigger cancer development, most studies ignore the degree of mucus adhesion at sampling. Therefore, we evaluated whether bacteria adhering to tissues could be identified by removing the outer mucus layer. Our 16S rRNA gene sequencing analysis of 18 surgical specimens of human colorectal cancer revealed that Sutterella (P = 0.045) and Enterobacteriaceae (P = 0.045) were significantly enriched in the mucus covering the mucosa relative to the mucosa. Rikenellaceae (P = 0.026) was significantly enriched in the mucus covering cancer tissues compared with those same cancer tissues. Ruminococcaceae (P = 0.015), Enterobacteriaceae (P = 0.030), and Erysipelotrichaceae (P = 0.028) were significantly enriched in the mucus covering the mucosa compared with the mucus covering cancers. Fusobacterium (P = 0.038) was significantly enriched in the mucus covering cancers compared with the mucus covering the mucosa. Comparing the microbiomes of mucus and tissues with mucus removed may facilitate identifying bacteria that genuinely invade tissues and affect tumorigenesis.
Efficacy of laryngeal mask airway against postoperative pharyngolaryngeal complications following thyroid surgery: a systematic review and meta-analysis of randomized controlled studies
Authors: Hung Kuo-Chuan , Wu Shao-Chun , Hsu Chih-Wei , Ko Ching-Chung , Chen Jui-Yi , Huang Ping-Wen , Chen I.-Wen , Sun Cheuk-Kwan 
Published: October 2022

AbstractThis meta-analysis aimed at investigating the effectiveness of laryngeal mask airway (LMA) against postoperative pharyngolaryngeal complications after thyroidectomy. MEDLINE, Cochrane Library, google scholar, and EMBASE databases were searched from inception through February, 2021, for randomized controlled trials (RCTs) comparing the incidence of pharyngolaryngeal complications following the use of LMA or endotracheal tube (ETT). Pooled results from seven RCTs involving 600 patients showed an association of LMA with a reduced risk of postoperative sore throat (POST) at 24 h [risk ratio (RR) 0.75,p = 0.006, four trials], but not at 1 h and 48 h after thyroidectomy. POST severity and hoarseness risk were lower in the LMA group than the ETT group at 1 h, 24 h, and 48 h (allp < 0.05). Nevertheless, hoarseness severity was lower in the LMA group only at postsurgical 48 h [standardized mean difference = − 0.35,p = 0.008, three trials]. Moreover, the risk of emergence cough was lower in patients using LMA than those receiving ETT (RR = 0.14,p = 0.002, two trials). The two groups did not differ in the severity of dysphagia at postoperative 1 h, 24 h, and 48 h. This meta-analysis showed that LMA may be associated with fewer pharyngolaryngeal complications compared to ETT without airway impacts. The limited number of included studies warrants further research to support our findings.
Systematic review and meta-analysis on physical barriers to prevent root dentin demineralization
Authors: Wierichs R. J. , Müller T. , Campus G. , Carvalho T. S. , Niemeyer S. H. 
Published: October 2022

AbstractThe present review systematically analyzed in vitro and in situ studies investigating physical diffusion barriers (sealants, desensitizer or adhesives) to prevent the development or the progression of root (dentin) demineralization. Three electronic databases (PubMed-Medline, CENTRAL, Ovid-EMBASE) were screened for studies from 1946 to 2022. Cross-referencing was used to identify further articles. Article selection and data abstraction were done in duplicate. Languages were not restricted. The type of outcome was not restricted, and their mean differences (MD) were calculated using fixed- or random-effects models. Risk of Bias was graded using Risk of Bias 2.0 tool. From 171 eligible studies, 34 were selected for full-text analysis evaluating 69 different materials, and 17 studies—still evaluating 36 different materials—were included (3 in situ and 14 in vitro). Ten studies evaluated desensitizers; 8 adhesives; and 1 infiltration. Meta-analyses were possible for all 17 studies. Meta-analyses revealed that lesion depth after no treatment was significantly higher than after the application of single-step adhesives (MD[95%CI] = − 49.82[− 69.34; − 30.30]) and multi-step adhesives (MD[95%CI]=–60.09 [–92.65, –27.54]). No significant differences in the lesion depth increase between single- and multi-step adhesives could be observed (MD[95%CI]=30.13 [–21.14, 81.39]). Furthermore, compared to no treatment the increase of the lesion depth was significantly hampered using desensitizers (MD[95%CI] = − 38.02[− 51.74; − 24.31]). Furthermore, the included studies presented unclear or high risk. A physical diffusion barrier can significantly hamper the increase of lesion depth under cariogenic conditions. Furthermore, multi-step adhesives seem not to be more effective than single-step adhesives. However, this conclusion is based on only few in vitro and in situ studies.
Bulked segregant transcriptome analysis in pea identifies key expression markers for resistance to Peyronellaea pinodes
Authors: Fondevilla Sara , Krezdorn Nicolas , Rubiales Diego , Rotter Björn , Winter Peter 
Published: October 2022

AbstractPeyronellaea pinodes is a devastating pathogen of pea crop. Quantitative trait loci (QTL) associated with resistance have been identified, as well as genes differentially expressed between resistant and susceptible pea lines. The key question is which of these many genes located into these QTLs, or differentially expressed, are the key genes that distinguish resistant from susceptible plants and could be used as markers. To identify these key genes, in the present study we applied MACE (Massive Analysis of cDNA Ends) -Seq to a whole Recombinant Inbred Line population segregating for resistance to this disease and their parental lines and identified those genes which expression was more correlated with the level of resistance. We also compared gene expression profiles between the most resistant and the most susceptible families of the RIL population. A total of 6780 transcripts were differentially expressed between the parental lines after inoculation. Of them, 803 showed the same expression pattern in the bulks formed by the most resistant and most susceptible RIL families. These genes, showing a consistent expression pattern, could be used as expression markers to distinguish resistant from susceptible plants. The analysis of these genes also discovered the crucial mechanisms acting against P. pinodes.
A 3-step approach to predict advanced fibrosis in nonalcoholic fatty liver disease: impact on diagnosis, patient burden, and medical costs
Authors: Kobayashi Takashi , Ogawa Yuji , Shinoda Satoru , Iwaki Michihiro , Nogami Asako , Honda Yasushi , Kessoku Takaomi , Imajo Kento , Yoneda Masato , Saito Satoru , Yamamoto Kouji , Oeda Satoshi , Takahashi Hirokazu , Sumida Yoshio , Nakajima Atsushi 
Published: October 2022

AbstractA 2-step approach, Fibrosis-4 index (FIB-4) followed by vibration-controlled transient elastography (VCTE), has been proposed to predict advanced fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). We aimed to develop a novel 3-step approach for predicting advanced fibrosis. We enrolled 284 biopsy-confirmed NAFLD patients from two tertiary care centers and developed subgroups (n = 190), including 3.7% of patients with advanced fibrosis, assuming a primary care setting. In the 3-step approach, patients with intermediate-to-high FIB-4 in the first step underwent an enhanced liver fibrosis test or measurement of type IV collagen 7S domain as the second step, and VCTE was performed if the second step value was higher than the cutoff. In 284 cases, a tertiary care cohort with 36.3% advanced fibrosis, the 3-step approach showed significantly higher specificity and positive predictive value than the 2-step approach. In the subgroup with 3.7% advanced fibrosis, the 3-step approach significantly reduced the referral rate to specialists, the number of high-risk patients (i.e., liver biopsy candidates), and healthcare costs by 12.5% to 15.8%. The 3-step approach may improve the diagnostic performance to predict advanced fibrosis in NAFLD, which could lower rates of referrals to specialists, liver biopsies, and medical costs.