bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Figure S1 (continued) from Whole-genome and epigenomic landscapes of malignant gastrointestinal stromal tumors harboring KIT exon 11 557–558 deletion mutations
Authors: Ohshima Keiichi , Nagashima Takeshi , Fujiya Keiichi , Hatakeyama Keiichi , Watanabe Yuko , Morimoto Kimiko , Kamada Fukumi , Shimoda Yuji , Ohnami Sumiko , Naruoka Akane , Serizawa Masakuni , Ohnami Shumpei , Kenmotsu Hirotsugu , Shiomi Akio , Tsubosa Yasuhiro , Bando Etsuro , Sugiura Teiichi , Sugino Takashi , Terashima Masanori , Uesaka Katsuhiko , Urakami Kenichi , Akiyama Yasuto , Yamaguchi Ken
Published: April 2023

Circos plots of the 30 GIST genomes in our study cohort.
Table S4 from Predicting Cancer Risk from Germline Whole-exome Sequencing Data Using a Novel Context-based Variant Aggregation Approach
Authors: Guan Zoe , Begg Colin B. , Shen Ronglai
Published: April 2023

Table S4: Significant predictors from individual association analyses based on WES data. The significance threshold for each cancer type was 0.05/n, where n is the number of predictors tested for the cancer type (ranging from 2541 for kidney to 2596 for breast).
Table S2 from Predicting Cancer Risk from Germline Whole-exome Sequencing Data Using a Novel Context-based Variant Aggregation Approach
Authors: Guan Zoe , Begg Colin B. , Shen Ronglai
Published: April 2023

Table S2: Polygenic risk scores used in SNP models (obtained from the Polygenic Score Catalog).
Table S3 from Systemic LRG1 expression in melanoma is associated with disease progression and recurrence
Authors: Hoefsmit Esmee P. , Völlmy Franziska , Rozeman Elisa A. , Reijers Irene L. M. , Versluis Judith M. , Hoekman Liesbeth , van Akkooi Alexander C. J. , Long Georgina V. , Schadendorf Dirk , Dummer Reinhard , Altelaar Maarten , Blank Christian U.
Published: April 2023

Table S3 shows the patient characteristics PRADO
Figure S4 from Systemic LRG1 expression in melanoma is associated with disease progression and recurrence
Authors: Hoefsmit Esmee P. , Völlmy Franziska , Rozeman Elisa A. , Reijers Irene L. M. , Versluis Judith M. , Hoekman Liesbeth , van Akkooi Alexander C. J. , Long Georgina V. , Schadendorf Dirk , Dummer Reinhard , Altelaar Maarten , Blank Christian U.
Published: April 2023

Figure S4 shows the serum analysis using Olink proteomic assay
Supplemental Figure 6 from Treatment Patterns and Outcomes of Pre-operative Neoadjuvant Radiotherapy in Patients with Early-onset Rectal Cancer
Authors: Badesha Jasleen K , Zhou Marilyn , Arif Arif A , Gill Sharlene , Speers Caroline , Peacock Michael , De Vera Mary A , Stuart Heather C , Brown Carl J , Donellan Fergal , Loree Jonathan M
Published: April 2023

Supplemental Figure 6. Disease-specific disease-free survival (DSDFS) for early-stage rectal cancer receiving neoadjuvant short-course radiotherapy with non-colorectal deaths censored (DSDFS).
Figure SF8 from Plexin-B1 Mutation Drives Metastasis in Prostate Cancer Mouse Models
Authors: Shorning Boris , Trent Neil , Griffiths David F. , Worzfeld Thomas , Offermanns Stefan , Smalley Matthew J. , Williamson Magali
Published: April 2023

Metastatic deposits in Ptenfl/flKrasG12VPlxnB1-/- mice
Figure SF6 from Plexin-B1 Mutation Drives Metastasis in Prostate Cancer Mouse Models
Authors: Shorning Boris , Trent Neil , Griffiths David F. , Worzfeld Thomas , Offermanns Stefan , Smalley Matthew J. , Williamson Magali
Published: April 2023

Metastatic deposits in Ptenfl/flp53fl/fl mice
Figure SF2 from Plexin-B1 Mutation Drives Metastasis in Prostate Cancer Mouse Models
Authors: Shorning Boris , Trent Neil , Griffiths David F. , Worzfeld Thomas , Offermanns Stefan , Smalley Matthew J. , Williamson Magali
Published: April 2023

Expression of PlexinB1 in mouse prostate and tumours
Supplementary Figure FS1 from Distinct IDH1/2-associated Methylation Profile and Enrichment of TP53 and TERT Mutations Distinguish Dedifferentiated Chondrosarcoma from Conventional Chondrosarcoma
Authors: Dermawan Josephine Kam Tai , Nafa Khedoujia , Mohanty Abhinita , Xu Yingjuan , Rijo Ivelise , Casanova Jacklyn , Villafania Liliana , Benhamida Jamal , Kelly Ciara M. , Tap William D. , Boland Patrick J. , Fabbri Nicola , Healey John H. , Ladanyi Marc , Lu Chao , Hameed Meera
Published: April 2023

Overall and progression-free survival in DDCS patients with or without TERT alterations
Supplementary Table S1 from Structurally complex osteosarcoma genomes exhibit limited heterogeneity within individual tumors and across evolutionary time
Authors: Rajan Sanjana , Zaccaria Simone , Cannon Matthew , Cam Maren , Gross Amy C , Raphael Benjamin J , Roberts Ryan D.
Published: April 2023

Characteristics of patient samples used in this study
Supplementary Figure S3 from Structurally complex osteosarcoma genomes exhibit limited heterogeneity within individual tumors and across evolutionary time
Authors: Rajan Sanjana , Zaccaria Simone , Cannon Matthew , Cam Maren , Gross Amy C , Raphael Benjamin J , Roberts Ryan D.
Published: April 2023

Ploidy plots
Supplementary Figure S2 from Structurally complex osteosarcoma genomes exhibit limited heterogeneity within individual tumors and across evolutionary time
Authors: Rajan Sanjana , Zaccaria Simone , Cannon Matthew , Cam Maren , Gross Amy C , Raphael Benjamin J , Roberts Ryan D.
Published: April 2023

CHISEL output plots
Table TS1 from Detection of MET Polysomy by Next-generation Sequencing and Its Clinical Relevance for MET Inhibitors
Authors: Sun Boyang , Qiu Tian , Zeng Xiaoling , Duan Jianchun , Bai Hua , Xu Jiachen , Li Jin , Li Junling , Hao Xuezhi , Liu Yutao , Lin Lin , Wang Hongyu , Zhang Xin , Zhong Jia , Wang Jie , Ying Jianming , Wang Zhijie
Published: April 2023

Clinicopathologic characteristics of patients in cohort 3.
Figure S4 from Detection of MET Polysomy by Next-generation Sequencing and Its Clinical Relevance for MET Inhibitors
Authors: Sun Boyang , Qiu Tian , Zeng Xiaoling , Duan Jianchun , Bai Hua , Xu Jiachen , Li Jin , Li Junling , Hao Xuezhi , Liu Yutao , Lin Lin , Wang Hongyu , Zhang Xin , Zhong Jia , Wang Jie , Ying Jianming , Wang Zhijie
Published: April 2023

One MET-FISH polysomy tumor was classified as negative using the NGS assay.
Data from Inhibiting ERK5 Overcomes Breast Cancer Resistance to Anti-HER2 Therapy By Targeting the G1–S Cell-Cycle Transition
Authors: Zhang Jingwei , Pearson Adam J. , Sabherwal Nitin , Telfer Brian A. , Ali Nisha , Kan Karmern , Xu Qiuping , Zhang Wei , Chen Fuhui , Li Shiyang , Wang Jinhua , Gray Nathanael S. , Risa-Ebrí Blanca , Finegan Katherine G. , Cross Michael J. , Giurisato Emanuele , Whitmarsh Alan J. , Tournier Cathy
Published: April 2023

Targeting HER2 has become a landmark in the treatment of HER2-driven breast cancer. Nonetheless, the clinical efficacy of anti-HER2 therapies can be short-lived and a significant proportion of patients ultimately develop metastatic disease and die. One striking consequence of oncogenic activation of HER2 in breast cancer cells is the constitutive activation of the extracellular-regulated protein kinase 5 (ERK5) through its hyperphosphorylation. In this study, we sought to decipher the significance of this unique molecular signature in promoting therapeutic resistance to anti-HER2 agents. We found that a small-molecule inhibitor of ERK5 suppressed the phosphorylation of the retinoblastoma protein (RB) in HER2-positive breast cancer cells. As a result, ERK5 inhibition enhanced the antiproliferative activity of single-agent anti-HER2 therapy in resistant breast cancer cell lines by causing a G1 cell-cycle arrest. Moreover, ERK5 knockdown restored the antitumor activity of the anti-HER2 agent lapatinib in human breast cancer xenografts. Taken together, these findings support the therapeutic potential of ERK5 inhibitors to improve the clinical benefit that patients receive from targeted HER2 therapies.
Significance:
Here we demonstrate that targeting ERK5 in HER2-positive breast cancer cells reduces the level of phosphorylation of RB, an important mediator of the G1–S transition. This effect is associated with increased antitumor activity of lapatinib in combination therapy with ERK5 silencing. Collectively, these findings reveal that ERK5 constitutes a relevant therapeutic target for the many patients with resistant HER2-positive breast cancer.
Data from Replication Stress Defines Distinct Molecular Subtypes Across Cancers
Authors: Takahashi Nobuyuki , Kim Sehyun , Schultz Christopher W. , Rajapakse Vinodh N. , Zhang Yang , Redon Christophe E. , Fu Haiqing , Pongor Lorinc , Kumar Suresh , Pommier Yves , Aladjem Mirit I. , Thomas Anish
Published: April 2023

Endogenous replication stress is a major driver of genomic instability. Current assessments of replication stress are low throughput precluding its comprehensive assessment across tumors. Here we develop and validate a transcriptional profile of replication stress by leveraging established cellular characteristics that portend replication stress. The repstress gene signature defines a subset of tumors across lineages characterized by activated oncogenes, aneuploidy, extrachromosomal DNA amplification, immune evasion, high genomic instability, and poor survival, and importantly predicts response to agents targeting replication stress more robustly than previously reported transcriptomic measures of replication stress. Repstress score profiles the dual roles of replication stress during tumorigenesis and in established cancers and defines distinct molecular subtypes within cancers that may be more vulnerable to drugs targeting this dependency. Altogether, our study provides a molecular profile of replication stress, providing novel biological insights of the replication stress phenotype, with clinical implications.
Significance:
We develop a transcriptional profile of replication stress which characterizes replication stress and its cellular response, revealing phenotypes of replication stress across cancer types. We envision the repstress score to serve as an effective discovery platform to predict efficacy of agents targeting replication stress and clinical outcomes.
Data from Chemical, Molecular, and Single-nucleus Analysis Reveal Chondroitin Sulfate Proteoglycan Aberrancy in Fibrolamellar Carcinoma
Authors: Francisco Adam B. , Li Jine , Farghli Alaa R. , Kanke Matt , Shui Bo , Munn Paul R. , Grenier Jennifer K. , Soloway Paul D. , Wang Zhangjie , Reid Lola M. , Liu Jian , Sethupathy Praveen
Published: April 2023

Fibrolamellar carcinoma (FLC) is an aggressive liver cancer with no effective therapeutic options. The extracellular environment of FLC tumors is poorly characterized and may contribute to cancer growth and/or metastasis. To bridge this knowledge gap, we assessed pathways relevant to proteoglycans, a major component of the extracellular matrix. We first analyzed gene expression data from FLC and nonmalignant liver tissue (n = 27) to identify changes in glycosaminoglycan (GAG) biosynthesis pathways and found that genes associated with production of chondroitin sulfate, but not other GAGs, are significantly increased by 8-fold. We then implemented a novel LC/MS-MS based method to quantify the abundance of different types of GAGs in patient tumors (n = 16) and found that chondroitin sulfate is significantly more abundant in FLC tumors by 6-fold. Upon further analysis of GAG-associated proteins, we found that versican (VCAN) expression is significantly upregulated at the mRNA and protein levels, the latter of which was validated by IHC. Finally, we performed single-cell assay for transposase-accessible chromatin sequencing on FLC tumors (n = 3), which revealed for the first time the different cell types in FLC tumors and also showed that VCAN is likely produced not only from FLC tumor epithelial cells but also activated stellate cells. Our results reveal a pathologic aberrancy in chondroitin (but not heparan) sulfate proteoglycans in FLC and highlight a potential role for activated stellate cells.
Significance:
This study leverages a multi-disciplinary approach, including state-of-the-art chemical analyses and cutting-edge single-cell genomic technologies, to identify for the first time a marked chondroitin sulfate aberrancy in FLC that could open novel therapeutic avenues in the future.
Data from Comprehensive Characterization of the Multiple Myeloma Immune Microenvironment Using Integrated scRNA-seq, CyTOF, and CITE-seq Analysis
Authors: Yao Lijun , Jayasinghe Reyka G. , Lee Brian H. , Bhasin Swati S. , Pilcher William , Doxie Deon Bryant , Gonzalez-Kozlova Edgar , Dasari Surendra , Fiala Mark A. , Pita-Juarez Yered , Strausbauch Michael , Kelly Geoffrey , Thomas Beena E. , Kumar Shaji K. , Cho Hearn Jay , Anderson Emilie , Wendl Michael C. , Dawson Travis , D'souza Darwin , Oh Stephen T. , Cheloni Giulia , Li Ying , DiPersio John F. , Rahman Adeeb H. , Dhodapkar Kavita M. , Kim-Schulze Seunghee , Vij Ravi , Vlachos Ioannis S. , Mehr Shaadi , Hamilton Mark , Auclair Daniel , Kourelis Taxiarchis , Avigan David , Dhodapkar Madhav V. , Gnjatic Sacha , Bhasin Manoj K. , Ding Li
Published: April 2023

As part of the Multiple Myeloma Research Foundation (MMRF) immune atlas pilot project, we compared immune cells of multiple myeloma bone marrow samples from 18 patients assessed by single-cell RNA sequencing (scRNA-seq), mass cytometry (CyTOF), and cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) to understand the concordance of measurements among single-cell techniques. Cell type abundances are relatively consistent across the three approaches, while variations are observed in T cells, macrophages, and monocytes. Concordance and correlation analysis of cell type marker gene expression across different modalities highlighted the importance of choosing cell type marker genes best suited to particular modalities. By integrating data from these three assays, we found International Staging System stage 3 patients exhibited decreased CD4+ T/CD8+ T cells ratio. Moreover, we observed upregulation of RAC2 and PSMB9, in natural killer cells of fast progressors compared with those of nonprogressors, as revealed by both scRNA-seq and CITE-seq RNA measurement. This detailed examination of the immune microenvironment in multiple myeloma using multiple single-cell technologies revealed markers associated with multiple myeloma rapid progression which will be further characterized by the full-scale immune atlas project.
Significance:
scRNA-seq, CyTOF, and CITE-seq are increasingly used for evaluating cellular heterogeneity. Understanding their concordances is of great interest. To date, this study is the most comprehensive examination of the measurement of the immune microenvironment in multiple myeloma using the three techniques. Moreover, we identified markers predicted to be significantly associated with multiple myeloma rapid progression.
Data from Under-Representation of Racial Groups in Genomics Studies of Gastroenteropancreatic Neuroendocrine Neoplasms
Authors: Herring Brendon R. , Bonner Andrew , Guenter Rachael E. , Vickers Selwyn , Yates Clayton , Lee Goo , Dhall Deepti , Chen Herbert , Rose J. Bart
Published: April 2023

Not all populations are poised to benefit from advancing genomics in gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN), as genomics have focused on White patients. This study aimed to evaluate racial populations represented in genomic studies of GEP-NENs and to provide evidence of differential genomic findings between racial groups in GEP-NENs. Manuscripts analyzing DNA, RNA, or DNA methylation in GEP-NENs were queried using PUBMED and EMBASE. NIH race/ethnicity term frequency was then determined by Natural Language Processing, followed by manual evaluation of tumor types and subjects by racial group. IHC of institutional tissue micro-arrays and analysis of AACR GENIE data analyzed was performed to determine mutational differences between Black and White pancreatic NEN (pNEN) patients. 313 manuscripts conducted the requisite genomic analyses, 16 of which included subject race data. Race data were included in 13/184 DNA, 4/107 RNA, and 1/54 DNA Methylation analyses. These studies included 89% White subjects (n = 2032), 5.8% Asian subjects (n = 132), 4.0% “Other” subjects (n = 93), and 1.2% Black subjects (n = 27). No Native American/Alaska Native, Native Hawaiian/Pacific Islander, or ethnically Hispanic/Latinx subjects were represented. There were significant differences in MEN1 mutations among Black and White patients in immunohistochemical (13:40) and GENIE data (24:268 patients per group, respectively), with 9 additional genes differentially mutated in the GENIE dataset. Genomic sequencing data for GEP-NENs is almost racially homogenous. Differences in pNEN genomics may exist between racial groups, highlighting a need for diversity in future genomic analyses of GEP-NENs to understand the putative influence of interracial genomic variation on GEP-NEN prevention, diagnosis, and therapy.
Significance:
There is little diversity in genomic studies of GEP-NENs, which may exhibit clinically impactful variation in their tumor biology among racial groups. Improved diversity in such studies is imperative for understanding this variation and its potential impacts on disease prevention, diagnosis, therapeutic targeting, and clinical outcomes.
CCL3 as Possible Negative Prognostic Factor in Chronic Lymphocytic Leukemia
Authors: Popek-Marciniec Sylwia , Zmorzyński Szymon , Koczkodaj Dorota , Marciniec Michał , Wąsik-Szczepanek Ewa , Karczmarczyk Agnieszka , Michalak-Wojnowska Małgorzata , Filip Agata
Published: April 2023

Introduction: Both microenvironmental signals from surrounding cells and changes in the genome of leukemic cells play essential role in the development of chronic lymphocytic leukemia. Nurse-like cells (NLCs) are one of the important elements of the microenvironment of CLL cells. The key role in the interactions of leukemic cells with NLCs is played by chemokines, which may interfere with the programmed cell death process in the leukemic lymphocytes. The aim of our study was analysis of selected microenvironmental factors having a potential impact on the leukemic cells survival, as well as their association with clinical, cytogenetic, and molecular parameters. For this study, we selected three types of molecules which can modulate microenvironment: chemokines IL-8 and CCL3 (which are classically secreted to extracellular matrix), soluble forms of adhesion molecules JAG1 and CD163, and secreted form of endogenous protein BIRC5. We assessed their expression in the serum of CLL patients as well as in medium of long-term NLCs cultures. Methods: Long-term cell culture was prepared from mononuclear cells derived from the blood of 34 patients with CLL. Number of NLCs cells was evaluated, under a light inverted microscope. The concentration of IL-8, CCL3, sBIRC5, sCD163, and sJAG1 in culture medium and serum was assessed by enzyme-linked immunosorbent assays. Results: There were significant differences in the concentration of IL-8, sBIRC5, CCL3, sCD163, and sJAG1 between the patient’s blood serum and the culture medium. The concentrations of IL-8, CCL3, and JAG1 were higher in the culture medium, which confirmed the role of the microenvironment in the production of these proteins. In addition, the concentration of CCL3 chemokine in both patient’s blood serum and in the culture medium correlated with the number of NLCs and with known prognostic factors in the course of CLL, e.g., Rai stage, WBC, expression of ZAP-70, CD38, and CD5/19. Conclusion: The microenvironment of CLL cells, which includes NLCs, plays an important role in the pathogenesis of CLL. The CCL3 chemokine seems to be a good factor representing microenvironment of CLL cells. Chronic lymphocytic leukemia is a complex and very heterogeneous disease; therefore, its progress should be considered both in the context of genetic changes and the interaction with microenvironmental cells.
Genomic Investigation of Remission and Relapse of Psychotic Depression Treated with Sertraline plus Olanzapine: The STOP-PD II Study
Authors: Men Xiaoyu , Marshe Victoria , Elsheikh Samar S. , Alexopoulos George S. , Marino Patricia , Meyers Barnett S. , Mulsant Benoit H. , Rothschild Anthony J. , Voineskos Aristotle N. , Whyte Ellen M. , Kennedy James Lowery , Flint Alastair J. , Müller Daniel J.
Published: April 2023

Introduction: Little is known regarding genetic factors associated with treatment outcome of psychotic depression. We explored genomic associations of remission and relapse of psychotic depression treated with pharmacotherapy. Methods: Genomic analyses were performed in 171 men and women aged 18–85 years with an episode of psychotic depression who participated in the Study of the Pharmacotherapy of Psychotic Depression II (STOP-PD II). Participants were treated with open-label sertraline plus olanzapine for up to 12 weeks; those who achieved remission or near-remission and maintained it following 8 weeks of stabilization were eligible to participate in a 36-week randomized controlled trial that compared sertraline plus olanzapine with sertraline plus placebo in preventing relapse. Results: There were no genome-wide significant associations with either remission or relapse. However, at a suggestive threshold, SNP rs1026501 (31 kb from SYNPO2) in the whole sample and rs6844137 (within the intronic region of SYNPO2) in the European ancestry subsample were associated with a decreased likelihood of remission. In polygenic risk analyses, participants who had greater improvement after antidepressant treatments showed a higher likelihood of reaching remission. Those who achieved remission and had a higher polygenic risk for Alzheimer’s disease had a significantly decreased likelihood of relapse. Conclusion: Our analyses provide preliminary insights into the genetic architecture of remission and relapse in a well-characterized group of patients with psychotic depression.
The Effect of Teacher’s Teaching Style in Araling Panlipunan on Student’s Motivation of Grade 8 Students in Sta. Cruz South High School
Authors: Ofiaza Evangeline S.
Published: April 2023

The study shows that shows, out of ninety (90) respondents, there is an equal number of respondents when grouped according to gender. The study revealed that 80% of the respondents acknowledge the importance effective teaching styles to motivate the students. The stiudy further confirm that 3.7% of the respondents, considered Araling Panlipunan fun and interesting.   It was also confirmed in the study that 3.8% of the respondents participated actively in Araling Panlipunan. The study revealed that majority of the respondents had the view that having effective teaching-styles in motivating students had a high impact on the academic performance. Based on the findings of the study, the following recommendations are made:Faculty staffs are encouraged to adapt new trends of teaching in order to inspire our students embracing Araling Panlipunan subject. It is further recommended that Araling Panlipunan teachers should not  only using a pen and paper materials in teaching, instead think of an effective materials  were in students become more motivated in exploring ideas like projectors and more. Conduct future studies to develop more teaching styles to motivate students to study Araling Panlipunan.
Leadership in the Neurosciences
Authors: Greer David M. , Leslie‐Mazwi Thabele
Published: April 2023

In this article regarding leadership as a vascular specialist, we describe how to understand personal strengths and weaknesses as a leader and what resources are available to assist in leadership, particularly in the neurosciences. We discuss how to assemble a team, build its culture, and get the most out of a group in such settings as running a successful meeting and setting goals for the group. We delve into the importance of diversity and setting an inclusive vision for a group so that all feel valued and respected. We explore such difficult topics as how to have difficult conversations with a team or its members, how to align financial goals and mission with the hospital and medical school, and how to lead through a crisis.
A Blanket That Leaves the Feet Cold: Exploring the AI Act Safety Framework for Medical AI
Authors: Palmieri Sofia , Goffin Tom
Published: April 2023

The AI Act is based on, and at the same time aims to protect fundamental rights, implying their protection, while fulfilling the safety requirement prescribed by the AI Act within the whole lifecycle of AI systems. Based on a risk classification, the AI Act provides a set of requirements that each risk class must meet in order for AI to be legitimately offered on the EU market and be considered safe. However, despite their classification, some minimal risk AI systems may still be prone to cause risks to fundamental rights and user safety, and therefore require attention. In this paper we explore the assumption that despite the fact that the AI Act can find broad ex litteris coverage, the significance of this applicability is limited.
Kathu Pan 6: Observations on the First Known Buried High-Density Open-Air Holocene Occupation on the Southern Margin of the Kalahari Basin
Authors: Black Wendy , Chiwara-Maenzanise Precious , Horwitz Liora Kolska , Walker Steven James , Chazan Michael
Published: April 2023

This paper presents preliminary results from a newly excavated open-air Later Stone Age site attributed to the Wilton Industry at Kathu Pan 6 in the Northern Cape Province of South Africa. Basic data on the lithics, fauna (including a large ivory fragment), and ostrich eggshell (including beads) recovered during two seasons of excavation (2016–2017) are presented and this material is contextualized through comparison with neighboring sites. Spatial analysis of the artifact distribution from the small exposure from the 2017 season suggests a spatially structured occupation. The Wilton open-air occupation of Kathu Pan 6 offers a new perspective on the poorly understood Later Stone Age of the southern fringes of the Kalahari.
Description of a new genus and new species of deep-water stenopodid shrimp from the western Atlantic, with remarks on Odontozona Holthuis, 1946 and Richardina A. Milne-Edwards, 1881 (Decapoda: Stenopodidea)
Authors: ANKER ARTHUR
Published: April 2023

A new genus, Jogoya, gen. nov., is established for a new species of stenopodid shrimp, Jogoya alucia sp. nov., the holotype and single specimen of which was collected during a manned submersible dive in the Bahamas in 2019, and two additional specimens collected during earlier expeditions, one also from the Bahamas and one from Anguilla. The new genus appears to occupy an intermediate position between Richardina A. Milne-Edwards, 1881 and Odontozona Holthuis, 1946. Jogoya gen. nov. is characterised by the presence of unusually large spines on the cervical cincture of the carapace, a feature shared with a species originally described as Odontozona foresti Hendrickx, 2002 and herein tentatively transferred to Jogoya gen. nov., as Jogoya foresti (Hendrickx, 2002), comb. nov. The most conspicuous morphological difference between J. alucia sp. nov. and J. foresti is in the armature of the posterior half of the carapace, with the latter species having a post-cervical cincture armed with strong spines, which is absent in the new species. The two species of Jogoya gen. nov. also differ greatly by their colour patterns.
Control Technology for Power Edge-Side Equipment Coordination to Suppress Power Fluctuations in Multiple Application Scenarios
Authors: Hu Yifei , Yan Long , Liu Shuang
Published: April 2023

In order to meet the power control requirements of power grids in multiple application scenarios, a control technology for power edge-side equipment coordination to suppress power fluctuations in multiple application scenarios is proposed. Firstly, the structure of distributed photovoltaic
connected to AC microgrid in multiple application scenarios is analyzed, and the power fluctuation of inverters and filter energy storage inductance components is analyzed to determine the type of photovoltaic power generation power edge side equipment in multiple application scenarios. On
this basis, the power fluctuation target is analyzed, and the power control target function is constructed. It predicts the short-term smoothing power of power edge-side devices in multiple application scenarios, and realizes the coordinated power fluctuation control of power edge-side devices
in multiple application scenarios based on the vector regulation domain. The experimental results show that the system loss of the method in this paper is small in the fluctuation suppression scenario and typical application scenario, the power fluctuation of the three methods meets the requirements
of the national standard, the power of the equipment on the power edge side is relatively stable, and the output power is between 218–224 MW fluctuation, and the power fluctuation rate is small, the maximum power fluctuation rate is 1.5%.
Adding venetoclax to lenalidomide and rituximab is safe and effective in patients with untreated mantle cell lymphoma
Authors: Phillips Tycel J. , Bond David , Takiar Radihka , Kump Karson , Kandarpa Malalthi , Boonstra Philip , Mayer Tera Lynn , Nachar Victoria , Wilcox Ryan A. , Carty Shannon A. , Karimi Yasmin H. , Nikolovska-Coleska Zaneta , Kaminski Mark S. , Herrera Alex F. , Maddocks Kami , Popplewell Leslie , Danilov Alexey V.
Published: April 2023

Mantle cell lymphoma (MCL) is a rare, incurable hematological malignancy with a heterogeneous presentation and clinical course. A wide variety of chemotherapy-based regimens are currently used in patients who are untreated. Over the last several years, several targeted or small-molecule therapies have shown efficacy in the relapsed/refractory setting and have since been explored in the frontline setting. Lenalidomide plus rituximab was explored in a phase 2 study of 38 patients with MCL who were untreated and ineligible to receive transplantation, in which the combination produced durable remissions. We looked to build upon this regimen by adding venetoclax to the combination. We conducted a multicenter, open-label, nonrandomized, single-arm study to evaluate this combination. We enrolled 28 unselected patients with untreated disease irrespective of age, fitness, or risk factors. Lenalidomide was dosed at 20 mg daily from days 1 to 21 of each 28-day cycle. The dose of venetoclax was determined using the time-to-event continual reassessment method. Rituximab was dosed at 375 mg/m2 weekly, starting on cycle 1, day 1 until cycle 2, day 1. No dose-limiting toxicities were noted. All patients were treated with venetoclax at the maximum tolerated dose of 400 mg daily. The most common adverse events were neutropenia and thrombocytopenia. The overall and complete response rates were 96% and 86%, respectively. In total, 86% of patients achieved minimal residual disease undetectability via next-generation sequencing. The median overall and progression-free survivals were not reached. The combination of lenalidomide, rituximab, and venetoclax is a safe and effective regimen in patients with untreated MCL. This trial was registered at www.clinicaltrials.gov as #NCT03523975.
Bimetallic Co–Fe sulfide and phosphide as efficient electrode materials for overall water splitting and supercapacitor
Authors: Bhardwaj Shiva , Srivastava Rishabh , Mageto Teddy , Chaudhari Mahesh , Kumar Anuj , Sultana Jolaikha , Mishra Sanjay R. , Perez Felio , Gupta Ram K.
Published: April 2023

The major center of attraction in renewable energy technology is the designing of an efficient material for both electrocatalytic and supercapacitor (SC) applications. Herein, we report the simple hydrothermal method to synthesize cobalt-iron-based nanocomposites followed by sulfurization and phosphorization. The crystallinity of nanocomposites has been confirmed using X-ray diffraction, where crystalline nature improves from as-prepared to sulfurized to phosphorized. The as-synthesized CoFe-nanocomposite requires 263 mV overpotential for oxygen evolution reaction (OER) to reach a current density of 10 mA/cm2 whereas the phosphorized requires 240 mV to reach 10 mA/cm2. The hydrogen evolution reaction (HER) for CoFe-nanocomposite exhibits 208 mV overpotential at 10 mA/cm2. Moreover, the results improved after phosphorization showing 186 mV to reach 10 mA/cm2. The specific capacitance (Csp) of as-synthesized nanocomposite is 120 F/g at 1 A/g, along with a power density of 3752 W/kg and a maximum energy density of 4.3 Wh/kg. Furthermore, the phosphorized nanocomposite shows the best performance by exhibiting 252 F/g at 1 A/g and the highest power and energy density of 4.2 kW/kg and 10.1 Wh/kg. This shows that the results get improved more than twice. The 97% capacitance retention after 5000 cycles shows cyclic stability of phosphorized CoFe. Our research thus offers cost-effective and highly efficient material for energy production and storage applications.
Differential splicing of neuronal genes in a Trem2*R47H mouse model mimics alterations associated with Alzheimer’s disease
Authors: Pandey Ravi S. , Kotredes Kevin P. , Sasner Michael , Howell Gareth R. , Carter Gregory W.
Published: April 2023

Background

Molecular characterization of late-onset Alzheimer’s disease (LOAD), the leading cause of age-related dementia, has revealed transcripts, proteins, and pathway alterations associated with disease. Assessing these postmortem signatures of LOAD in experimental model systems can further elucidate their relevance to disease origins and progression. Model organisms engineered with human genetic factors further link these signatures to disease-associated variants, especially when studies are designed to leverage homology across species. Here we assess differential gene splicing patterns in aging mouse models carrying humanizedAPOE4and/or theTrem2*R47Hvariant on a C57BL/6J background. We performed a differential expression of gene (DEG) and differential splicing analyses on whole brain transcriptomes at multiple ages. To better understand the difference between differentially expressed and differentially spliced genes, we evaluated enrichment of KEGG pathways and cell-type specific gene signatures of the adult brain from each alteration type. To determine LOAD relevance, we compared differential splicing results from mouse models with multiple human AD splicing studies.

Results

We found that differentially expressed genes inTrem2*R47Hmice were significantly enriched in multiple AD-related pathways, including immune response, osteoclast differentiation, and metabolism, whereas differentially spliced genes were enriched for neuronal related functions, including GABAergic synapse and glutamatergic synapse. These results were reinforced by the enrichment of microglial genes in DEGs and neuronal genes in differentially spliced genes inTrem2*R47Hmice. We observed significant overlap between differentially spliced genes inTrem2*R47Hmice and brains from human AD subjects. These effects were absent inAPOE4mice and suppressed inAPOE4.Trem2*R47Hdouble mutant mice relative toTrem2*R47Hmice.

Conclusions

The cross-species observation that alternative splicing observed in LOAD are present inTrem2*R47Hmouse models suggests a novel link between this candidate risk gene and molecular signatures of LOAD in neurons and demonstrates how deep molecular analysis of new genetic models links molecular disease outcomes to a human candidate gene.
A novel C19ORF12 mutation in two MPAN sisters treated with deferiprone
Authors: Chen Sihui , Lai Xiaohui , Fu Jiajia , Yang Jing , Zhao Bi , Shang Huifang , Huang Rui , Chen Xueping
Published: April 2023

Background

Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a rare and devastating disease caused by pathogenic mutations inC19orf12gene. MPAN is characterized by pathological iron accumulation in the brain and fewer than 100 cases of MPAN have been described. Although the diagnosis of MPAN has achieved a great breakthrough with the application of the whole exome gene sequencing technology, the therapeutic effect of iron chelation therapy in MPAN remains controversial.

Case presentation

We reported that two sisters from the same family diagnosed with MPAN had dramatically different responses to deferiprone (DFP) treatment. The diagnosis of MPAN were established based on typical clinical manifestations, physical examination, brain magnetic resonance imaging (MRI), cerebrospinal fluid analysis (CSF) and gene sequencing results. The clinical presentations of the two sisters with MPAN due to novel gene locus mutations were similar to those previously reported. There is no other difference in basic information except that the proband had a later onset age and fertility history. Both the proband and his second sister were treated with deferiprone (DFP), but they had dramatically different responses to the treatment. The proband’s condition deteriorated sharply after treatment with DFP including psychiatric symptoms and movement disorders. However, the second sister of the proband became relatively stable after receiving the DFP treatment. After four years of follow-up, the patient still denies any new symptoms of neurological deficits.

Conclusion

The findings of this study enriched the MPAN gene database and indicated that DFP might ameliorate symptom progression in patients without severe autonomic neuropsychiatric impairment at the early stage of the disease.
Plasma ctDNA increases tissue NGS-based detection of therapeutically targetable mutations in lung cancers
Authors: Xie Jianjiang , Yao Weishen , Chen Lingxiu , Zhu Wenjun , Liu Qiang , Geng Geng , Fang Jing , Zhao Yang , Xiao Li , Huang Zhenhua , Zhao Jing
Published: April 2023

Background

Circulating tumor DNA (ctDNA) has been becoming a novel convenient and noninvasive method for dynamically monitoring landscape of genomic information to guild personalized cancer treatment. In this study we comprehensively evaluated the additional value of plasma ctDNA to routine tissue next generation sequencing (NGS) of therapeutically targetable mutations in lung cancers.

Methods

The tumor tissues and peripheral blood samples from 423 cases of patients with lung cancer were subjected to NGS of mutations in oncodrivers (EGFR, ERBB2, ALK, ROS1, C-MET, KRAS, BRAF, RET, BRCA1 and BRCA2).

Results

One hundred and ninety-seven cases showed both plasma and tissue positive and 96 showed both negative. The concordance for tissue and blood detection was 69.27% (293/423). 83 (19.62%) cases showed positive by tissue NGS alone and 47 (11.11%) positive by plasma ctDNA alone. The sensitivity of tissue and plasma detection was 85.63%, and 74.62%, respectively. Plasma had lower detection and sensitivity than tissue, but plasma additionally detected some important mutations which were omitted by tissue NGS. Plasma plus tissue increased the detection rate of 66.19% by tissue alone to 77.30% as well as the sensitivity of 85.63–100%. Similar results were also observed when the cases were classified into subpopulations according to different stages (IV vs. III vs. I-II), grades (low vs. middle grade) and metastatic status (metastasis vs. no metastasis).

Conclusion

Plasma ctDNA shares a high concordance with tissue NGS, and plasma plus tissue enhances the detection rate and sensitivity by tissue alone, implying that the tissue and plasma detection should be mutually complementary in the clinical application.
Application of the pedicle axis view in percutaneous screw placement for type III fracture dislocation of the sacroiliac joint
Authors: Zhao Zhongzhen , Zheng Guofu , Chu Xiaodong , Wang Shuofan
Published: April 2023

Aim

To investigate the clinical application of axial view projection of the pedicle in percutaneous screw placement for type III fracture dislocation of the sacroiliac joint.

Methods

Percutaneous sacroiliac screw fixation was performed in 29 patients with type III sacroiliac joint fractures under X-ray fluoroscopy (C-arm) using axial view projection of the pedicle after preoperative traction reduction and preoperative preparation. The study included 19 males and 10 females, aged 20 to 75 years old, with a mean age of 42.1 ± 3.4 years.

Results

The total operative time ranged between 44 and 135 min, with a mean of 95.5 ± 9.4 min. The intraoperative fluoroscopy time ranged between 15 and 42 s, with a mean of 25 ± 4.7 s. The intraoperative blood loss ranged between 5 and 10 ml, with a mean of 7.1 ± 1.3 ml. According to the Matta scoring system, excellent outcomes were achieved in 25 cases, whereas good outcomes were achieved in 4 cases. Based on the definition by Neo et al., pedicle screw positions were categorized into four grades: grade 0 (33 screws), grade I (2 screws), grade II (2 screws), and grade III (0 screws). Excellent outcomes were achieved in 94.6% of Grade 0 and I screws. According to Majeed’s functional score, 21 cases achieved excellent outcomes, whereas 8 cases achieved good outcomes. The 29 patients were followed between 3 and 18 months, with a mean of 7.1 ± 1.2 months. All patients achieved anatomical reduction with accurate screw placement and successful healing of their fractures, with no cases of bone penetration or neurovascular injury.

Conclusion

Axial view imaging of the pedicle using fluoroscopy is a convenient and rapid fluoroscopy method for percutaneous screw placement for type III fracture dislocation of the sacroiliac joint, with a high rate of success, good safety, and short fluoroscopy time.
Evaluating a clinical decision support point of care instrument in low resource setting
Authors: Tegenaw Geletaw Sahle , Amenu Demisew , Ketema Girum , Verbeke Frank , Cornelis Jan , Jansen Bart
Published: April 2023

Background

Clinical pathways are one of the main tools to manage the health care’s quality and concerned with the standardization of care processes. They have been used to help frontline healthcare workers by presenting summarized evidence and generating clinical workflows involving a series of tasks performed by various people within and between work environments to deliver care. Integrating clinical pathways into Clinical Decision Support Systems (CDSSs) is a common practice today. However, in a low-resource setting (LRS), this kind of decision support systems is often not readily accessible or even not available. To fill this gap, we developed a computer aided CDSS that swiftly identifies which cases require a referral and which ones may be managed locally. The computer aided CDSS is designed primarily for use in primary care settings for maternal and childcare services, namely for pregnant patients, antenatal and postnatal care. The purpose of this paper is to assess the user acceptance of the computer aided CDSS at the point of care in LRSs.

Methods

For evaluation, we used a total of 22 parameters structured in to six major categories, namely “ease of use, system quality, information quality, decision changes, process changes, and user acceptance.” Based on these parameters, the caregivers from Jimma Health Center's Maternal and Child Health Service Unit evaluated the acceptability of a computer aided CDSS. The respondents were asked to express their level of agreement using 22 parameters in a think-aloud approach. The evaluation was conducted in the caregiver's spare-time after the clinical decision. It was based on eighteen cases over the course of two days. The respondents were then asked to score their level of agreement with some statements on a five-point scale: strongly disagree, disagree, neutral, agree, and strongly agree.

Results

The CDSS received a favorable agreement score in all six categories by obtaining primarily strongly agree and agree responses. In contrast, a follow-up interview revealed a variety of reasons for disagreement based on the neutral, disagree, and strongly disagree responses.

Conclusions

Though the study had a positive outcome, it was limited to the Jimma Health Center Maternal and Childcare Unit, and hence a wider scale evaluation and longitudinal measurements, including computer aided CDSS usage frequency, speed of operation and impact on intervention time are needed.
Use of LARS for soft tissue function reconstruction during tumor-type hemi-shoulder replacement achieves a good prognosis: a retrospective cohort study
Authors: Tong Xiaopeng , He Hongbo , Zhang Can , Liu Yupeng , Zeng Hao , Qiu Xinzhu , Liu Qing
Published: April 2023

Background

Shoulder soft tissue function reconstruction during tumor-type hemishoulder replacement is an important step to restore shoulder function. This study evaluates the functional prognosis and postoperative complications of ligament advanced reinforcement system (LARS)-assisted soft tissue functional reconstruction in tumor-type hemi-shoulder replacement.

Materials and methods

Twenty-two patients with an average age of 37.5 ± 17.8 years diagnosed with benign invasive tumors, primary malignant bone tumors, or bone metastases were enrolled in this study. The patient’s medical records (history and surgical details), histological sections, imaging files, oncological prognosis, functional prognosis, and postoperative complications were collected. The upper limb function and shoulder joint function were evaluated using the Musculoskeletal Tumor Society (MSTS) system and American Shoulder and Elbow Surgeons (ASES) scoring criteria, respectively.

Results

Twenty-two patients comprising 12 males and 10 females were enrolled. Overall, 9 patients had preoperative pathological fractures. The mean lesion length was 8.6 ± 3.0 cm. The local recurrence was observed in 3 cases, including 2 cases of osteosarcoma and 1 case of MGCT. A further 4 cases had pulmonary metastasis, including 2 cases with local tumor recurrence. The average postoperative MSTS score was 25.8 ± 1.7, and the score of postoperative ASES was 85.7 ± 6.0, both of which showed satisfactory functional recovery. Two cases experienced postoperative complications requiring surgical intervention, including one periprosthetic fracture and one giant cell granuloma. Prosthesis dislocation occurred in 1 case. None of the cases of periprosthetic infection or postoperative complications resulted in implant failure.

Conclusions

LARS-assisted soft tissue function reconstruction in benign and malignant proximal humerus tumors after a tumor-type hemi-shoulder replacement is an effective technical improvement, which can effectively repair the integrity of the joint capsule to restore joint stability, provide a medium for soft tissue attachment to rebuild the muscular dynamic system, and eliminate residual dead space around the prosthesis, effectively improving limb function and reduce postoperative infection complications.
Socio-cultural attitudes toward the body as a predictor of motivation for physical activity in young people brought up in Asian and European culture—Chinese-Polish comparison
Authors: Guo Shuai , Izydorczyk Bernadetta , Lipowska Małgorzata , Kamionka Agata , Lizińczyk Sebastian , Sajewicz-Radtke Urszula , Radtke Bartosz M. , Liu Taofeng , Lipowski Mariusz
Published: April 2023

The influence of sociocultural attitudes toward the body on young people’s physical activity has received increasing attention. However, there is a lack of cross-cultural research in this area. The main aim of this research was to identify the similarities and differences in the sociocultural attitudes toward the body of Polish and Chinese young people who grew up in European and Asian cultures and to analyze their effect on the motivation for physical activity. A cross-sectional research study was conducted among 18- to 30-year-old Polish (n = 259) and Chinese (n = 208) young people. The variables were measured using the Sociocultural Attitudes towards Appearance Questionnaire 3 (SATAQ 3) and the Inventory of Physical Activity Objectives (IPAO). Descriptive and comparative statistics, Spearman’s rho, and the stepwise multiple regression analysis were used. The main analysis showed There are both similarities and significant differences in the performance of young Polish and Chinese men and women on the variables studied; Internalization-Athlete, Pressures, and Internalization-General are universal sociocultural predictors of motivation for physical activity among young people in Poland and China; Information is a specific sociocultural predictor of motivation for physical activity in Polish young people. The cultural nuances need to be considered in understanding young people’s Motivation for undertaking physical activity.