bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring a Link Between Alzheimer’s and Glioma by Investigating SORL1 Network
Authors: Montalbo Kristy , Bakker Emyr , Stasik Izabela , Smith Christopher 
Published: October 2022

Abstract

AIMS
Use bioinformatics methods to identify and validate associated proteins and genes in the SORL1 network. Generate a bank of patient derived cells in association with the Royal Preston Hospital BTNW tissue bank. Explore identified targets from the bioinformatics in patient derived cells.

METHOD
Proteins and genes associated with SORL1 and SORLA were identified on GeneCards. Connectivity mapping of known and predicted interactions linked to SORL1 was explored in STRING. For clinical validation differential expression was investigated by comparing genomic data from GTEX and TCGA, available at Xenabrowser. For survival analysis Kaplan-Meier curves were generated on cBioPortal. The five most differently expressed novel targets are taken forward for laboratory experiments using western blots for protein quantification and immunocytochemistry to identify and visualise target proteins.

RESULTS
A total of 73 genes (30 from GeneCards and 43 from STRING) were obtained. 63 genes from the generated SORL1-related network were shown to be differentially expressed whilst 40 were significantly different between low-surviving patients and high-surviving patients. The top five associated proteins are CKAP4, CTNND1, FN1, HSPA12A and SORCS3. CKAP4, CTNND1 and FN1 are highly expressed in both glioma and glioblastoma, but low expressed in healthy tissue. HSPA12A is low expressed in cancerous brain tissue and highly expressed in healthy samples. SORCS3 is differentially expressed in healthy samples and glioma, but significantly low expressed glioblastoma.

CONCLUSION
This project provides insight into SORL1 molecular relationships and function in tissue, cultured cells and serum from a patient cohort including demographics, disease progression and site.
Agreement Between Measures of Adherence to Isoniazid Preventive Therapy Among People With HIV in Uganda
Authors: Forman Leah S , Lodi Sara , Fatch Robin , Emenyonu Nneka I , Adong Julian , Ngabirano Christine , Jacobson Karen R , Gerona Roy , Reckers Andrew R , Gandhi Monica , Muyindike Winnie R , Hahn Judith A 
Published: October 2022

Abstract

Background
Isoniazid (INH) preventative therapy is recommended for people with HIV (PWH) in resource-constrained settings. Valid measures are needed to assess adherence. We aimed to examine agreement between measures overall and by level of social desirability.

Methods
PWH with latent tuberculosis (TB) were recruited in Mbarara, Uganda. Past 30-day adherence was measured by the number of days with pill bottle openings using a medication event monitoring system (MEMS) and self-reported number of days pills taken. INH concentration (INH plus acetyl INH and their ratio) in hair samples was measured. We used Bland-Altman plots to examine agreement between adherence measures and calculated the area under the receiver operating characteristics curve (AUROC) to determine if INH hair concentration predicted optimal MEMS-measured adherence (≥90%).

Results
A total of 301 participants enrolled; 92% were virologically suppressed, and adherence was high. The median (interquartile range [IQR]) number of pill bottle openings in 30 days was 28 (24–30) compared with 30 (28–30) via self-report. The median INH concentration (IQR) was 36.2 (17.2–62.4), and the INH:acetyl ratio was 2.43 (0.99–3.92). Agreement between self-reported and MEMS adherence was greater at more optimal adherence levels. INH:acetyl INH ratio was not predictive of optimal adherence according to MEMS (AUROC, 0.62; 95% CI, 0.52–0.72) in a subset (n = 161).

Conclusions
Lower MEMS adherence levels compared with self-report suggest the need for objective adherence measures. Biologic measures have potential, although in this study INH concentration was not predictive of MEMS measured adherence. More data are needed to assess the accuracy of biologic measures.
A Phase II Trial on Osimertinib as a First-Line Treatment for EGFR Mutation-Positive Advanced NSCLC in Elderly Patients: The SPIRAL-0 Study
Authors: Chihara Yusuke , Takeda Takayuki , Goto Yasuhiro , Nakamura Yoichi , Tsuchiya-Kawano Yuko , Nakao Akira , Onoi Keisuke , Hibino Makoto , Fukuda Minoru , Honda Ryoichi , Yamada Takahiro , Taniguchi Ryusuke , Sakamoto Sinjiro , Date Koji , Nagashima Seiji , Tanzawa Shigeru , Minato Koichi , Nakatani Koichi , Izumi Miiru , Shimose Takayuki , Kishimoto Junji , Uchino Junji , Takayama Koichi 
Published: October 2022

Abstract

Background
Osimertinib is one of the standard first-line treatments for advanced non-small cell lung cancer in patients with epidermal growth factor receptor (EGFR) mutations, because it achieves significantly longer progression-free survival (PFS) than conventional first-line treatments (hazard ratio: 0.46). However, the efficacy and safety of osimertinib as a first-line treatment for patients aged ≥75 years remain unclear.

Methods
This phase II study was performed to prospectively investigate the efficacy and safety of osimertinib for elderly patients with EGFR mutation-positive advanced non-small cell lung cancer. The primary endpoint was 1-year PFS rate; secondary endpoints were overall response rate (ORR), PFS, overall survival (OS), and safety.

Results
Thirty-eight patients were included in the analysis. The 1-year PFS rate was 59.4% (95% confidence interval [CI], 46.1%-72.7%), which did not meet the primary endpoint (the threshold 1-year PFS rate of 50% predicted using data from the NEJ003 study). The most common grade 3/4 adverse events were rash/dermatitis acneiform/ALT increased/hypokalemia (2 patients, 5%). Seven patients developed pneumonitis (17.5%). There were no other cases of treatment discontinuation due to adverse events other than pneumonitis.

Conclusion
Although this study did not meet the primary endpoint, osimertinib was tolerable for elderly patients with EGFR mutation-positive advanced non-small cell lung cancer. (Japan Registry of Clinical Trials [JRCT] ID number: jRCTs071180007).
Radiotherapy Plus Temozolomide With or Without Nimotuzumab Against the Newly Diagnosed EGFR-Positive Glioblastoma: A Retrospective Cohort Study
Authors: She Lei , Gong Xuan , Su Lin , Liu Chao 
Published: October 2022

Abstract

Background
Glioblastoma (GBM) has a poor prognosis, and patients with epidermal growth factor receptor (EGFR) amplification have an even worse prognosis. Nimotuzumab is an EGFR monoclonal antibody thought to play a significant role in the treatment of GBM. This paper presents a retrospective cohort study that evaluates the clinical efficacy and safety of nimotuzumab in GBM.

Materials and Methods
A total of 56 newly diagnosed patients with EGFR-positive GBM were included in our study. The patients were divided into radiotherapy (RT) + temozolomide (TMZ) + nimotuzumab (39 patients) and RT + TMZ (17 patients) groups based on whether or not nimotuzumab was added during RT. Progression-free survival (PFS), overall survival (OS), and toxicities were assessed.

Results
The median follow-up time was 27.9 months (95% confidence interval [CI], 25.1-30.8). The median PFS was 12.4 months (95% CI, 7.8-17.0) and 8.2 months (95% CI, 6.1-10.3) in the 2 groups, respectively, P = .052. The median OS was 27.3 months (95% CI, 19.0-35.6) and 16.7 months (95% CI, 11.1-22.2), respectively, P = .018. In patients with unmethylated O6-methylguanine-DNA methyltransferase (MGMT) promoter, the PFS and OS were significantly better in patients treated with nimotuzumab than in those without nimotuzumab (median PFS: 19.3 vs 6.7 months, P = .001; median OS: 20.2 vs 13.8 months, P = .026). During the treatment period, no statistically significant difference in toxicity was noted between the 2 groups.

Conclusion
Our retrospective cohort study suggests the efficacy of Nimotuzumab combined with concurrent RT with TMZ in patients with newly diagnosed EGFR-positive GBM, and specifically those with unmethylated MGMT promoter. Further prospective studies are warranted to validate our findings. Besides, nimotuzumab demonstrated good safety and tolerability.
Behavioral Political Science
Authors: James Patrick 
Published: October 2022

Abstract
Behavioral political science (BPS) is a research enterprise with many accomplishments in place already, such as rigorous concept formation and a wide range of theories that have performed well under various kinds of testing. This chapter, which evaluates the contents of the present volume, unfolds in eight sections. The first section provides an overview of how assessment of BPS will be carried out. Sections two through five review the accomplishments of the major sectors in the present volume: a) bounded rationality and heuristics, b) theories, c) attitudes, and d) methods. The sixth section introduces systemism, a graphic approach toward representation of cause and effect. The seventh section applies systemism in an effort to assemble the contributions from sectors a through d into a visual representation of cause and effect for BPS. An eighth and final section reflects on what has been achieved.
When Queer Theory Goes to Law School
Authors: Cossman Brenda 
Published: October 2022

Abstract
Queer theory developed as an interrogation of the multiple discursive productions of sexuality, seeking to denaturalize the assumed connections between sex, gender, and desire. It did so in part as a break from the prevailing analytic frameworks for theorizing around sexuality. This chapter outlines the emergence of queer theory and some of its distinctive themes and critical sensibilities, highlighting its shared genealogies with feminism as well as its break from it. We consider what queer theory is against, what queer theory is for, and what it has to say about law. The chapter explores how queer legal theory differs from a more rights-based approach to LGBT issues by focusing on the Supreme Court’s decisions in the sodomy challenges and the same-sex marriage challenge.
Dominance Feminism
Authors: Abrams Kathryn 
Published: October 2022

Abstract
Dominance feminism offered a new theorization of sex and gender inequality, which described sexualization and sexual coercion as the linchpin of women’s subordination and offered law as a tool for remedying it, notably through the Title VII claim for sexual harassment. However, critiques by feminists of color, sex-positive feminists, and others exposed the limits of dominance theory’s engagement with intersectional experiences of sexual violence and women’s agency under circumstances of constraint. The advent of #MeToo returned sexualized injury to the fore and bolstered dominance feminism’s predominantly sociological approach with plural, solidaristic experiential narratives. Although some proponents of #MeToo have demonstrated a greater appreciation of women’s sexual agency amidst their resistance to sexual injury, whether #MeToo can capture the varieties of sexualized violence, as they are experienced on the streets or in low-wage or nonprofessional workplaces, remains an ongoing question.
Hyper-CVAD-Based Stem Cell Microtransplant as Post-Remission Therapy in Acute Lymphoblastic Leukemia
Authors: Cai Bo , Wang Yi , Lei Yangyang , Shi Yanping , Sun Qiyun , Qiao Jianhui , Hu Kaixun , Lei Yaqing , Li Bingxia , Liu Tieqiang , Liu Zhiqing , Yao Bo , Zhao Xuecong , Li Xiaofei , Zhao Wen , Feng Xiujie , Xie Anli , Ning Xin , Feng Mingxing , Zhao Weiwei , Guo Jiayue , Ai Huisheng , Yu Changlin , Guo Mei 
Published: October 2022

Abstract
Post-remission strategies for patients with acute lymphoblastic leukemia (ALL) are limited to the multiagent chemotherapy and allogeneic stem cell transplant (allo-SCT), and cellular therapies are seldom involved. Although chemotherapy combined with mismatched granulocyte colony-stimulating factor mobilized peripheral blood mononuclear cell infusion (microtransplant, MST) has been studied in patients with acute myeloid leukemia, its efficacy in ALL is still undetermined. We enrolled 48 patients receiving hyper-CVAD-based MST between July 1, 2009, and January 31, 2018. No acute or chronic graft-versus-host disease occurred in patients receiving MST. Four-year overall survival (OS) and leukemia-free survival (LFS) were 62% and 35%, respectively, and the 4-year relapse rate was 65%. No patient experienced non–relapse mortality. Subgroup analysis showed that OS rates were comparable between groups with different age, risk stratification, minimal residual disease status prior to MST and immunophenotype. Adult patients tended to achieve better 4-year LFS (62% vs. 26%, P = .058) and lower hematologic relapse rate (38% vs. 74%, P = .058) compared with adolescent and young adult patients. Donor chimerism/microchimerism was detectable ranging from 0.002% to 42.78% in 78% (42/54) available samples within 14 days after each infusion and at 3 months or one year after the last cell infusion. Multivariate analyses demonstrated that white blood cells &lt;30 × 109/L at diagnosis and sufficient hyper-CVAD cycles were prognostic factors for better 4-year OS and LFS, while the B-cell phenotype and higher number of infused CD34+ cells in the first cycle were predictors for favorable 4-year LFS. The hyper-CVAD-based MST was a feasible strategy for treating ALL patients with mild toxicity.
Biomechanical Analysis of Cortical Bone Trajectory Screw Versus Bone Cement Screw for Fixation in Porcine Spinal Low Bone Mass Model
Authors: Li Yifan , Wang Silian , Zhu Zhenbiao , Chen Liwei , Shi Zhangpeng , Ye Xiaojian , Xu Wei , Li Zhikun 
Published: October 2022

Study Design:A prospective study of in vitro animal.Objection:To compare the biomechanics of cortical bone trajectory screw (CBT) and bone cement screw (BC) in an isolated porcine spinal low bone mass model.Summary of Background Data:The choice of spinal fixation in patients with osteoporosis remains controversial. Is CBT better than BC? Research on this issue is lacking.Methods:Ten porcine spines with 3 segments were treated with EDTA decalcification. After 8 weeks, all the models met the criteria of low bone mass. Ten specimens were randomly divided into groups, group was implanted with CBT screw (CBT group) and the other group was implanted with bone cement screw (BC group). The biomechanical material testing machine was used to compare the porcine spine activities of the two groups in flexion, extension, bending, and axial rotation, and then insertional torque, pull-out force, and anti-compression force of the 2 groups were compared. Independent sample t test was used for comparison between groups.Results:Ten 3 segments of porcine spine models with low bone mass were established, and the bone mineral density of all models was lower than 0.75 g/cm2. There is no difference between the CBT and BC groups in flexion, extension, bending, and axial rotation angle,P>0.05. However, there were significant differences between the 2 groups and the control group, withP＜0.01. The 2 groups significantly differed between the insertional torque (P=0.03) and the screw pull-out force (P=0.021). The anti-compression forces between the 2 groups have no significant difference between the two groups (P=0.946).Conclusions:The insertional torque and pull-out force of the CBT were higher than those of the BC in the isolated low bone porcine spine model. The range of motion and anti-compression ability of the model was similar between the 2 fixation methods.
Low-dimensional organization of global brain states of reduced consciousness
Authors: Perl Yonatan Sanz , Pallavicini Carla , Piccinini Juan , Demertzi Athena , Bonhomme Vincent , Martial Charlotte , Panda Rajanikant , Alnagger Naji , Annen Jitka , Gosseries Olivia , Ibañez Agustin , Laufs Helmut , Sitt Jacobo , Jirsa Viktor , Kringelbach Morten , Laureys Steven , Deco Gustavo , Tagliazucchi Enzo 
Published: October 2022

AbstractBrain states are frequently represented using a unidimensional scale measuring the richness of subjective experience (level of consciousness). This description assumes a mapping between the high-dimensional space of whole-brain configurations and the trajectories of brain states associated with changes in consciousness, yet this mapping and its properties remain unknown. We combined whole-brain modelling, data augmentation and deep learning for dimensionality reduction to determine a mapping representing states of consciousness in a low-dimensional space, where distances parallel similarities between states. An orderly trajectory from wakefulness to brain injured patients is revealed in a latent space whose coordinates represent metrics related to functional modularity and structure-function coupling, both increasing alongside loss of consciousness. Finally, we investigated the effects of model perturbations, providing geometrical interpretation for the stability and reversibility of states. We conclude that conscious awareness depends on functional patterns encoded as a low-dimensional trajectory within the vast space of brain configurations.
From comparative gene content and gene order to ancestral contigs, chromosomes and karyotypes
Authors: Xu Qiaoji , Jin Lingling , Zheng Chunfang , Zhang Xiaomeng , Leebens-Mack James , Sankoff David 
Published: October 2022

AbstractTo reconstruct the ancestral genome of a set of phylogenetically related descendant species, we use the Raccroche pipeline for organizing a large number of generalized gene adjacencies into contigs and then into chromosomes. Separate reconstructions are carried out for each ancestral node of the phylogenetic tree for focal taxa. The ancestral reconstructions are monoploids; they each contain at most one member of each gene family constructed from descendants, ordered along the chromosomes. We design and implement a new computational technique for solving the problem of estimating the ancestral monoploid number of chromosomes x. This involves a “g-mer” analysis to resolve a bias due long contigs, and gap statistics to estimate x. We find that the monoploid number of all the rosid and asterid orders is x = 9. We show that this is not an artifact of our method by deriving x ≈ 20 for the metazoan ancestor.
Detection of orthologous genes with expression shifts linked to nickel hyperaccumulation across Eudicots
Authors: Gallopin Mélina , Drevet Christine , de la Torre Vanesa S. Garcia , Jelassi Sarah , Michel Marie , Ducos Claire , Saule Cédric , Majorel Clarisse , Burtet-Sarramegna Valérie , Pillon Yohan , Bastide Paul , Lespinet Olivier , Merlot Sylvain 
Published: October 2022

AbstractThe remarkable capacity of plants to tolerate and accumulate tremendous amount of nickel is a complex adaptative trait that appeared independently in more than 700 species distributed in about fifty families. Nickel hyperaccumulation is thus proposed as a model to investigate the evolution of complex traits in plants. However, the mechanisms involved in nickel hyperaccumulation are still poorly understood in part because comparative transcriptomic analyses struggle to identify genes linked to this trait from a wide diversity of species. In this work, we have implemented a methodology based on the quantification of the expression of orthologous groups and phylogenetic comparative methods to identify genes which expression is correlated to the nickel hyperaccumulation trait. More precisely, we performed de novo transcriptome assembly and reads quantification for each species on its own transcriptome using available RNA-Seq datasets from 15 nickel hyperaccumulator and non-accumulator species. Assembled contigs were associated to orthologous groups built using proteomes predicted from completed plant genome sequences. We then analyzed the transcription profiles of 5953 orthologous groups from distant species using a phylogenetic ANOVA. We identified 31 orthologous groups with an expression shift associated with nickel hyperaccumulation. These orthologous groups correspond to genes that have been previously implicated in nickel accumulation, and to new candidates involved in this trait. We thus believe that this method can be successfully applied to identify genes linked to other complex traits from a wide diversity of species.
Tetraose steroidal glycoalkaloids from potato provide resistance againstAlternaria solaniand Colorado potato beetle
Authors: Wolters Pieter J. , Wouters Doret , Tikunov Yury M. , Ayilalath Shimlal , Kodde Linda P. , Strijker Miriam , Caarls Lotte , Visser Richard G. F. , Vleeshouwers Vivianne G. A. A. 
Published: October 2022

AbstractPlants with innate disease and pest resistance can contribute to more sustainable agriculture. Natural defence compounds produced by plants have the potential to provide a general protective effect against pathogens and pests, but they are not a primary target in resistance breeding. Here, we identified a wild relative of potato,Solanum commersonii, that provides us with unique insight in the role of glycoalkaloids in plant immunity. We cloned two atypical resistance genes that provide resistance toAlternaria solaniand Colorado potato beetle through the production of tetraose steroidal glycoalkaloids. Moreover, we providein vitroevidence to show that these compounds have potential against a range of different (potato pathogenic) fungi. This research links structural variation in steroidal glycoalkaloids to resistance against potato diseases and pests. Further research on the biosynthesis of plant defence compounds in different tissues, their toxicity, and the mechanisms for detoxification, can aid the effective use of such compounds to improve sustainability of our food production.
Identify the origin and end cells and infer the trajectory of cellular fate automatically
Authors: Zeng Zehua , Xing Cencan , Hu Lei , Roshan Shah , Xiong Yuanyan , Du Hongwu 
Published: October 2022

AbstractCellular state identification and trajectory inference enable reconstructions of cell fate dynamics from single-cell RNA sequencing. However, the identification of cell fate trajectories requires a large number of computational resources or known biological process, and lack a method to alleviate both of these deficiencies at the same time. Here, we present scLTNN, a method that automatically infers origin and end cell state from scRNA-seq data and calculates the developmental trajectory and differentiation direction of cells with only a few computational resources and time consummation. We apply scLTNN to disentangling subpopulation kinetics in CD8+ T cell, pancreatic endocrinogenesis, and the development of zebrafish embryos. scLTNN displays a strong trajectory inference ability cross-species. scLTNN features a modular design that can be flexibly extended to any scRNA-seq analysis task. The complete package is available online at https://github.com/Starlitnightly/scltnn.