bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Table 2 from Fresh Tissue Multi-omics Profiling Reveals Immune Classification and Suggests Immunotherapy Candidates for Conventional Chondrosarcoma
Authors: Li Binghao , Li Guoqi , Yan Xiaobo , Zhu Dan , Lin Patrick P. , Wang Zenan , Qu Hao , He Xuexin , Fu Yanbiao , Zhu Xiuliang , Lin Peng , Zhang Jiangnan , Li Xiaoya , Dai Hui , Chen Huabiao , Poznansky Mark C. , Lin Nong , Ye Zhaoming
Published: November 2024

Supplementary Table 2
Figure S7 from Fresh Tissue Multi-omics Profiling Reveals Immune Classification and Suggests Immunotherapy Candidates for Conventional Chondrosarcoma
Authors: Li Binghao , Li Guoqi , Yan Xiaobo , Zhu Dan , Lin Patrick P. , Wang Zenan , Qu Hao , He Xuexin , Fu Yanbiao , Zhu Xiuliang , Lin Peng , Zhang Jiangnan , Li Xiaoya , Dai Hui , Chen Huabiao , Poznansky Mark C. , Lin Nong , Ye Zhaoming
Published: November 2024

Figure S7
Figure S2 from Fresh Tissue Multi-omics Profiling Reveals Immune Classification and Suggests Immunotherapy Candidates for Conventional Chondrosarcoma
Authors: Li Binghao , Li Guoqi , Yan Xiaobo , Zhu Dan , Lin Patrick P. , Wang Zenan , Qu Hao , He Xuexin , Fu Yanbiao , Zhu Xiuliang , Lin Peng , Zhang Jiangnan , Li Xiaoya , Dai Hui , Chen Huabiao , Poznansky Mark C. , Lin Nong , Ye Zhaoming
Published: November 2024

Figure S2
Figure S1 from Fresh Tissue Multi-omics Profiling Reveals Immune Classification and Suggests Immunotherapy Candidates for Conventional Chondrosarcoma
Authors: Li Binghao , Li Guoqi , Yan Xiaobo , Zhu Dan , Lin Patrick P. , Wang Zenan , Qu Hao , He Xuexin , Fu Yanbiao , Zhu Xiuliang , Lin Peng , Zhang Jiangnan , Li Xiaoya , Dai Hui , Chen Huabiao , Poznansky Mark C. , Lin Nong , Ye Zhaoming
Published: November 2024

Figure S1
Supplementary Table S2 from First-In-Human Phase I Study of a Next-Generation, Oral, TGFβ Receptor 1 Inhibitor, LY3200882, in Patients with Advanced Cancer
Authors: Yap Timothy A. , Vieito Maria , Baldini Capucine , Sepúlveda-Sánchez Juan Manuel , Kondo Shunsuke , Simonelli Matteo , Cosman Rasha , van der Westhuizen Andre , Atkinson Victoria , Carpentier Antoine F. , Löhr Mario , Redman Rebecca , Mason Warren , Cervantes Andres , Le Rhun Emilie , Ochsenreither Sebastian , Warren Louise , Zhao Yumin , Callies Sophie , Estrem Shawn T. , Man Michael , Gandhi Leena , Avsar Emin , Melisi Davide
Published: November 2024

All causality TEAEs
Supplementary Table S1 from First-In-Human Phase I Study of a Next-Generation, Oral, TGFβ Receptor 1 Inhibitor, LY3200882, in Patients with Advanced Cancer
Authors: Yap Timothy A. , Vieito Maria , Baldini Capucine , Sepúlveda-Sánchez Juan Manuel , Kondo Shunsuke , Simonelli Matteo , Cosman Rasha , van der Westhuizen Andre , Atkinson Victoria , Carpentier Antoine F. , Löhr Mario , Redman Rebecca , Mason Warren , Cervantes Andres , Le Rhun Emilie , Ochsenreither Sebastian , Warren Louise , Zhao Yumin , Callies Sophie , Estrem Shawn T. , Man Michael , Gandhi Leena , Avsar Emin , Melisi Davide
Published: November 2024

Dosing and administration information
Data from The Novel Nucleoside Analogue ProTide NUC-7738 Overcomes Cancer Resistance Mechanisms In Vitro and in a First-In-Human Phase I Clinical Trial
Authors: Schwenzer Hagen , De Zan Erica , Elshani Mustafa , van Stiphout Ruud , Kudsy Mary , Morris Josephine , Ferrari Valentina , Um In Hwa , Chettle James , Kazmi Farasat , Campo Leticia , Easton Alistair , Nijman Sebastian , Serpi Michaela , Symeonides Stefan , Plummer Ruth , Harrison David J. , Bond Gareth , Blagden Sarah P.
Published: November 2024

AbstractPurpose:
Nucleoside analogues form the backbone of many therapeutic regimens in oncology and require the presence of intracellular enzymes for their activation. A ProTide is comprised of a nucleoside fused to a protective phosphoramidate cap. ProTides are easily incorporated into cells whereupon the cap is cleaved and a preactivated nucleoside released. 3′-Deoxyadenosine (3′-dA) is a naturally occurring adenosine analogue with established anticancer activity in vitro but limited bioavailability due to its rapid in vivo deamination by the circulating enzyme adenosine deaminase, poor uptake into cells, and reliance on adenosine kinase for its activation. In order to overcome these limitations, 3′-dA was chemically modified to create the novel ProTide NUC-7738.
Experimental Design:
We describe the synthesis of NUC-7738. We determine the IC50 of NUC-7738 using pharmacokinetics (PK) and conduct genome-wide analyses to identify its mechanism of action using different cancer model systems. We validate these findings in patients with cancer.
Results:
We show that NUC-7738 overcomes the cancer resistance mechanisms that limit the activity of 3′-dA and that its activation is dependent on ProTide cleavage by the enzyme histidine triad nucleotide-binding protein 1. PK and tumor samples obtained from the ongoing first-in-human phase I clinical trial of NUC-7738 further validate our in vitro findings and show NUC-7738 is an effective proapoptotic agent in cancer cells with effects on the NF-κB pathway.
Conclusions:
Our study provides proof that NUC-7738 overcomes cellular resistance mechanisms and supports its further clinical evaluation as a novel cancer treatment within the growing pantheon of anticancer ProTides.
Data from Functional Impact of Genomic Complexity on the Transcriptome of Multiple Myeloma
Authors: Ziccheddu Bachisio , Da Vià Matteo C. , Lionetti Marta , Maeda Akihiro , Morlupi Silvia , Dugo Matteo , Todoerti Katia , Oliva Stefania , D'Agostino Mattia , Corradini Paolo , Landgren Ola , Iorio Francesco , Pettine Loredana , Pompa Alessandra , Manzoni Martina , Baldini Luca , Neri Antonino , Maura Francesco , Bolli Niccolò
Published: November 2024

AbstractPurpose:
Multiple myeloma is a biologically heterogenous plasma-cell disorder. In this study, we aimed at dissecting the functional impact on transcriptome of gene mutations, copy-number abnormalities (CNA), and chromosomal rearrangements (CR). Moreover, we applied a geno-transcriptomic approach to identify specific biomarkers for personalized treatments.
Experimental Design:
We analyzed 514 newly diagnosed patients from the IA12 release of the CoMMpass study, accounting for mutations in multiple myeloma driver genes, structural variants, copy-number segments, and raw-transcript counts. We performed an in silico drug sensitivity screen (DSS), interrogating the Cancer Dependency Map (DepMap) dataset after anchoring cell lines to primary tumor samples using the Celligner algorithm.
Results:
Immunoglobulin translocations, hyperdiploidy and chr(1q)gain/amps were associated with the highest number of deregulated genes. Other CNAs and specific gene mutations had a lower but very distinct impact affecting specific pathways. Many recurrent genes showed a hotspot (HS)-specific effect. The clinical relevance of double-hit multiple myeloma found strong biological bases in our analysis. Biallelic deletions of tumor suppressors and chr(1q)-amplifications showed the greatest impact on gene expression, deregulating pathways related to cell cycle, proliferation, and expression of immunotherapy targets. Moreover, our in silico DSS showed that not only t(11;14) but also chr(1q)gain/amps and CYLD inactivation predicted differential expression of transcripts of the BCL2 axis and response to venetoclax.
Conclusions:
The multiple myeloma genomic architecture and transcriptome have a strict connection, led by CNAs and CRs. Gene mutations impacted especially with HS-mutations of oncogenes and biallelic tumor suppressor gene inactivation. Finally, a comprehensive geno-transcriptomic analysis allows the identification of specific deregulated pathways and candidate biomarkers for personalized treatments in multiple myeloma.
Data from Tumor Cell IDO Enhances Immune Suppression and Decreases Survival Independent of Tryptophan Metabolism in Glioblastoma
Authors: Zhai Lijie , Bell April , Ladomersky Erik , Lauing Kristen L. , Bollu Lakshmi , Nguyen Brenda , Genet Matthew , Kim Miri , Chen Peiwen , Mi Xinlei , Wu Jennifer D. , Schipma Matthew J. , Wray Brian , Griffiths John , Unwin Richard D. , Clark Simon J. , Acharya Rajesh , Bao Riyue , Horbinski Craig , Lukas Rimas V. , Schiltz Gary E. , Wainwright Derek A.
Published: November 2024

AbstractPurpose:
Glioblastoma (GBM) is an incurable primary brain tumor that has not benefited from immunotherapy to date. More than 90% of GBM expresses the tryptophan (Trp) metabolic enzyme, indoleamine 2,3-dioxygenase 1 (IDO). This observation supported the historical hypothesis that IDO suppresses the antitumor immune response solely through a mechanism that requires intratumoral Trp depletion. However, recent findings led us to investigate the alternative hypothesis that IDO suppresses the anti-GBM immune response independent of its association with Trp metabolism.
Experimental Design:
IDO-deficient GBM cell lines reconstituted with IDO wild-type or IDO enzyme–null cDNA were created and validated in vitro and in vivo. Microarray analysis was conducted to search for genes that IDO regulates, followed by the analysis of human GBM cell lines, patient GBM and plasma, and The Cancer Genome Atlas (TCGA) database. Ex vivo cell coculture assays, syngeneic and humanized mouse GBM models, were used to test the alternative hypothesis.
Results:
Nonenzymic tumor cell IDO activity decreased the survival of experimental animals and increased the expression of complement factor H (CFH) and its isoform, factor H like protein 1 (FHL-1) in human GBM. Tumor cell IDO increased CFH and FHL-1 expression independent of Trp metabolism. Increased intratumoral CFH and FHL-1 levels were associated with poorer survival among patients with glioma. Similar to IDO effects, GBM cell FHL-1 expression increased intratumoral regulatory T cells (Treg) and myeloid-derived suppressor cells while it decreased overall survival in mice with GBM.
Conclusions:
Our study reveals a nonmetabolic IDO-mediated enhancement of CFH expression and provides a new therapeutic target for patients with GBM.
Data from Ovarian Cancer–Specific BRCA-like Copy-Number Aberration Classifiers Detect Mutations Associated with Homologous Recombination Deficiency in the AGO-TR1 Trial
Authors: Schouten Philip C. , Richters Lisa , Vis Daniel J. , Kommoss Stefan , van Dijk Ewald , Ernst Corinna , Kluin Roelof J.C. , Marmé Frederik , Lips Esther H. , Schmidt Sandra , Scheerman Esther , Prieske Katharina , van Deurzen Carolien H.M. , Burges Alexander , Ewing-Graham Patricia C. , Dietrich Dimo , Jager Agnes , de Gregorio Nikolaus , Hauke Jan , du Bois Andreas , Nederlof Petra M. , Wessels Lodewyk F. , Hahnen Eric , Harter Philipp , Linn Sabine C. , Schmutzler Rita K.
Published: November 2024

AbstractPurpose:
Previously, we developed breast cancer BRCA1-like and BRCA2-like copy-number profile shrunken centroid classifiers predictive for mutation status and response to therapy, targeting homologous recombination deficiency (HRD). Therefore, we investigated BRCA1- and BRCA2-like classification in ovarian cancer, aiming to acquire classifiers with similar properties as those in breast cancer.

Experimental Design: We analyzed DNA copy-number profiles of germline BRCA1- and BRCA2-mutant ovarian cancers and control tumors and observed that existing breast cancer classifiers did not sufficiently predict mutation status. Hence, we trained new shrunken centroid classifiers on this set and validated them in the independent The Cancer Genome Atlas dataset. Subsequently, we assessed BRCA1/2-like classification and obtained germline and tumor mutation and methylation status of cancer predisposition genes, among them several involved in HR repair, of 300 ovarian cancer samples derived from the consecutive cohort trial AGO-TR1 (NCT02222883).
Results:
The detection rate of the BRCA1-like classifier for BRCA1 mutations and promoter hypermethylation was 95.6%. The BRCA2-like classifier performed less accurately, likely due to a smaller training set. Furthermore, three quarters of the BRCA1/2-like tumors could be explained by (epi)genetic alterations in BRCA1/2, germline RAD51C mutations and alterations in other genes involved in HR. Around half of the non–BRCA-mutated ovarian cancer cases displayed a BRCA-like phenotype.
Conclusions:
The newly trained classifiers detected most BRCA-mutated and methylated cancers and all tumors harboring a RAD51C germline mutations. Beyond that, we found an additional substantial proportion of ovarian cancers to be BRCA-like.
Data from Antitumor Activity of the Novel BTK Inhibitor TG-1701 Is Associated with Disruption of Ikaros Signaling in Patients with B-cell Non–Hodgkin Lymphoma
Authors: Ribeiro Marcelo Lima , Reyes-Garau Diana , Vinyoles Meritxell , Profitós Pelejà Núria , Santos Juliana Carvalho , Armengol Marc , Fernández-Serrano Miranda , Sedó Mor Alícia , Bech-Serra Joan J. , Blecua Pedro , Musulen Eva , De La Torre Carolina , Miskin Hari , Esteller Manel , Bosch Francesc , Menéndez Pablo , Normant Emmanuel , Roué Gaël
Published: November 2024

AbstractPurpose:
Despite the remarkable activity of BTK inhibitors (BTKi) in relapsed B-cell non–Hodgkin lymphoma (B-NHL), no clinically-relevant biomarker has been associated to these agents so far. The relevance of phosphoproteomic profiling for the early identification of BTKi responders remains underexplored.
Experimental Design:
A set of six clinical samples from an ongoing phase I trial dosing patients with chronic lymphocytic leukemia (CLL) with TG-1701, a novel irreversible and highly specific BTKi, were characterized by phosphoproteomic and RNA sequencing (RNA-seq) analysis. The activity of TG-1701 was evaluated in a panel of 11 B-NHL cell lines and mouse xenografts, including two NF-κB- and BTKC481S-driven BTKi-resistant models. Biomarker validation and signal transduction analysis were conducted through real-time PCR, Western blot analysis, immunostaining, and gene knockout (KO) experiments.
Results:
A nonsupervised, phosphoproteomic-based clustering did match the early clinical outcomes of patients with CLL and separated a group of “early-responders” from a group of “late-responders.” This clustering was based on a selected list of 96 phosphosites with Ikaros-pSer442/445 as a potential biomarker for TG-1701 efficacy. TG-1701 treatment was further shown to blunt Ikaros gene signature, including YES1 and MYC, in early-responder patients as well as in BTKi-sensitive B-NHL cell lines and xenografts. In contrast, Ikaros nuclear activity and signaling remained unaffected by the drug in vitro and in vivo in late-responder patients and in BTKC481S, BTKKO, and noncanonical NF-κB models.
Conclusions:
These data validate phosphoproteomic as a valuable tool for the early detection of response to BTK inhibition in the clinic, and for the determination of drug mechanism of action.
Data from Fresh Tissue Multi-omics Profiling Reveals Immune Classification and Suggests Immunotherapy Candidates for Conventional Chondrosarcoma
Authors: Li Binghao , Li Guoqi , Yan Xiaobo , Zhu Dan , Lin Patrick P. , Wang Zenan , Qu Hao , He Xuexin , Fu Yanbiao , Zhu Xiuliang , Lin Peng , Zhang Jiangnan , Li Xiaoya , Dai Hui , Chen Huabiao , Poznansky Mark C. , Lin Nong , Ye Zhaoming
Published: November 2024

AbstractPurpose:
There is still no standard nonsurgical regimen for conventional chondrosarcoma (CHS). We aimed to identify whether any CHSs have a favored microenvironment for immunotherapy via multidimensional evaluation of the immunologic characteristics of this tumor.
Experimental Design:
We obtained 98 newly-diagnosed CHS fresh tumors from several institutions and performed comprehensive analysis of data from CyTOF, whole-exome sequencing, and flow cytometry in 22 cases. Clinical data from immunotherapy responders and nonresponders were compared to explore possible biomarkers of immunotherapy response. Mechanism studies were conducted to interpret the biomarker phenotype.
Results:
Based on the integrated data of single-cell CyTOF and flow cytometry, the CHS immune-microenvironment phenotypes were classified into three groups: subtype I, the “granulocytic–myeloid-derived suppressor cell (G-MDSC) dominant” cluster, with high number of HLA-DR− CD14− myeloid cells; subtype II, the “immune exhausted” cluster, with high exhausted T-cell and dendritic-cell infiltration; and subtype III, the “immune desert” cluster, with few immune cells. Immune cell–rich subtypes (subtype I and II) were characterized by IDH mutation, pathologic high grade, and peritumoral edema, while subtype I cases were exclusively featured by myxoid transformation. In clinical practice involving 12 individuals who received PD-1 antibody immunotherapy, all of the 3 cases with controlled diseases were retrospectively classified as subtype II. In mechanism, IDH mutation significantly elevated chemokine levels and immune-cell infiltration in immune-inactivated tumors.
Conclusions:
This study is the first to provide immune characterization of CHS, representing a major step to precise immunotherapy against this malignancy. Immunotherapy is promising for the “immune exhausted” subtype of patients with CHS.
Figure 1 from Elraglusib Induces Cytotoxicity via Direct Microtubule Destabilization Independently of GSK3 Inhibition
Authors: Coats Josh T. , Li Shuyu , Tanaka Tomoyuki U. , Tauro Sudhir , Sutherland Calum , Saurin Adrian T.
Published: November 2024

Elraglusib causes a mitotic arrest. A and B, Example flow cytometry plots (A) and quantifications (B) showing the effect of 24-hour elraglusib (Elr) treatment on the percentage of 2N, 4N, and 4N-mitotic K299 WT cells. C and D, Example flow cytometry plots (C) and quantifications (D) following 24-hour treatments with two structurally distinct GSK3 inhibitors, CT99021 and LY2090314 in K299 WT cells. E and F, Example flow cytometry plots (E) and quantifications (F) showing the effect of 24-hour elraglusib (Elr) treatment on the percentage of 2N, 4N, and 4N-mitotic K299 GSK3A/B dual paralog shRNA knockdown cells (DKD). G and H, Total GSK3 immunoblot (G) with quantification confirming knockdown efficiency in K299 DKD compared with K299 WT cells (H). Cells were treated for 24 hours prior to cell-cycle analysis by flow cytometry using propidium iodide and anti–phospho-histone-H3 (Ser10) staining. Ten thousand events were analyzed per sample. Cell-cycle histograms are representative of three independent experiments, and quantifications combine three independent experiments. Immunoblot representative of three independent experiments; quantification was performed by normalizing to actin loading control and combines three independent experiments. Fold change calculated vs. control, error bars represent SEM, and statistical significance was determined using one-way ANOVA, with P ≤ 0.05. ns, not significant; *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001.
Die Zukunft der zielgerichteten Therapie des Leiomyosarkoms
Authors: Denu Ryan A. , Dann Amanda M. , Keung Emily Z. , Nakazawa Michael S. , Nassif Haddad Elise F.
Published: November 2024

Das Leiomyosarkom (LMS) ist ein aggressiver Subtyp des Weichteilsarkoms, der aus glatten Muskelzellen hervorgeht und am häufigsten im Uterus und im Retroperitoneum vorkommt. Das LMS ist eine heterogene Erkrankung mit unterschiedlichen klinischen und molekularen Merkmalen, die noch nicht vollständig verstanden sind. Die Erstellung molekularer Profile hat potenzielle Angriffspunkte für eine Behandlung aufgezeigt, wobei es bisher keine zugelassenen zielgerichteten Therapien für LMS gibt. In dieser Übersichtsarbeit werden historische und aktuelle Ergebnisse der molekularen Profilerstellung untersucht, vielversprechende Wege der aktuellen Forschung aufgezeigt und mögliche zukünftige Strategien vorgeschlagen, um dem Ziel einer molekular maßgeschneiderten Behandlung von LMS näher zu kommen. Wir konzentrieren uns auf die DNA-Schadensreaktion, die Makrophagen-reiche Mikroumgebung, den PI3K/mTOR-Signalweg, epigenetische Regulatoren und die Telomerbiologie.
Skin and Bone: Chronic Paronychia Leading to Osteomyelitis
Authors: de Vries Jonathan , Chung Mimi , Elewski Boni E.
Published: November 2024

Introduction: Paronychia can be both acute and chronic dependent on the chronicity of disease, with different etiologies linked to each. Acute paronychia is commonly secondary to bacterial infections, while chronic paronychia can be multifactorial and include inflammatory causes. Case Presentation: We present a case of chronic paronychia that developed into osteomyelitis of the affected finger. Conclusion: Because nail folds are anatomically close to the phalanges, it is important to monitor for worsening disease, as paronychia can develop into more serious infections.
Testing Forecast Rationality for Measures of Central Tendency
Authors: Dimitriadis Timo , Patton Andrew J. , Schmidt Patrick W.
Published: November 2024

Rational respondents to economic surveys may report as a point forecast any measure of the central tendency of their predictive distribution, e.g. the mean, median, or mode. We propose tests of forecast rationality when the measure used by the respondent is unknown. We overcome an identification problem that arises when the centrality measures are in a local neighborhood of each other, as is the case for approximately symmetric distributions. We apply our tests to income forecasts from the FRBNY's Survey of Consumer Expectations. We find these forecasts are rationalizable as mode forecasts, but not as mean or median forecasts.
Sorting and Wage Premiums in Immoral Work
Authors: Schneider Florian H. , Brun Fanny , Weber Roberto A.
Published: November 2024

We use surveys, laboratory experiments and administrative data to study how heterogeneity in the perceived immorality of work and in workers' aversion to acting immorally impact labor market outcomes. Immoral work is associated with higher wages, both in administrative data and in causal experimental evidence. Individuals more willing to engage in immoral conduct find employment in firms and industries perceived as immoral less aversive and have higher employment rates in immoral work in the laboratory. These phenomena appear to be driven by impure social motives, reflecting a desire not to be involved with immoral work, rather than by consequentialist concerns.
Student and Instructor Perceptions and Uses of Artificial Intelligence in Higher Education
Authors: Marshik Tesia , McCracken Christopher , Kopp Bryan , O’Marrah Morgan
Published: November 2024

Background

Artificial intelligence (AI) applications have recently become more powerful and accessible. There has been much discussion about the potential impacts of AI on learning and sample applications. Yet, little research exists on how and to what extent AI is being used in educational contexts.

Objective

The purpose of this study was to examine and compare students’ and instructors’ perceptions and uses of AI in educational settings.

Method

A sample of 113 undergraduate students and 71 instructors at a public university completed an online survey in which they reported how and how often they use AI for educational and instructional purposes and their views of its potential benefits and detriments to learning.

Results

Students and instructors reported relatively low AI usage, similar views on potential benefits and detriments to learning, and similar views on acceptable academic use. However, their perceptions diverged in several important ways.

Conclusion

This research highlights the need for policy, transparency, training, and nuanced discussions about how to use AI effectively and responsibly to promote learning goals.

Teaching Implications

The survey instruments developed for this study may be useful tools for facilitating conversations, clarifying expectations, and expanding understanding of AI uses in psychology programs.
Variable stroke fatigue test for aircraft landing gears
Authors: Chao Chen , Botao Hu , Xiangming Chen , Yanan Chai , Chun Zhang
Published: November 2024

The fixed stroke fatigue test cannot simulate the real loading conditions of the landing gear, and the variable stroke fatigue test has increasingly become mainstream. A modular test device for fatigue tests for aircraft landing gears was designed, and the automatic control of the buffer stroke was realized with ectopic displacement control technology effectively. The horizontal loading cylinder could follow the wheel axis actively with the displacement active control technology. The follow-up loading along the vertical direction was realized by constructing a polar coordinate system and making the loading line automatic alignment. A split-type dummy wheel was designed to improve the loading accuracy, and a booster cylinder was designed to realize the control loading of high pressure combined with the hydraulic control system. The test results show that the technical scheme meets the design requirements, and the fatigue test was completed successfully. The device for landing gear variable stroke fatigue testing is appropriate for other landing gear static/fatigue tests.
Investigating endwall flow mechanisms and improving the loss model under diverse operating conditions
Authors: Wang Jiahui , Zhang Hualiang , Yin Zhao , Liu Yu , Tang Hongtao , Xu Yujie , Chen Haisheng
Published: November 2024

Accurate prediction and comprehension of off-design turbine performance hold paramount importance in the development of highly efficient turbines capable of operating across a diverse range of conditions. This research concentrates on a highly loaded turbine cascade endwall flow and endeavors to scrutinize the impact of both incidence angle and inlet free stream turbulence intensity (FSTI). The investigation involves a meticulous analysis leading to substantial improvements in the existing endwall loss model (the Benner model correlated with the Moustapha incidence loss correction model), tailored for off-design scenarios. The findings underscore the pronounced influence of both incidence angle and FSTI on the dynamics of the endwall flow. Notably, alterations in the incidence angle have been identified as exerting a discernible impact on the flow structure, particularly when encountering large positive incidence angles. At an incidence angle of +20°, a distinctive vortex known as the Concentrated Shedding Vortex emerges as a pivotal factor in shaping the endwall flow structure, resulting in a substantial escalation in endwall losses. Furthermore, variations in FSTI predominantly affect the intensity of secondary vortices, thereby influencing endwall loss. Leveraging these discernments, an expressive formulation for endwall loss is derived by refining the higher-order terms of the incidence loss correction model and introducing a corrective term associated with FSTI. It has been validated that the proposed model controls the prediction error of endwall loss within a margin of ±0.02.
The Association of Interleukin 6 Receptor Gene Variant (Rs4129267) with Susceptibility to Ankylosing Spondylitis and Soluble IL-6 Receptor Level in Iranian Patients
Authors: Enayati Samaneh , Akhtari Maryam , Darabi Farideh , Ahmadzadeh Nooshin , Mostafaei Shayan , Vojgani Yousef , Madreseh Elham , Farhadi Elham , Akhlaghi Masoomeh , Jamshidi Ahmadreza , Mahmoudi Mahdi
Published: November 2024

Objectives:

Ankylosing spondylitis (AS) is an axial skeleton-related auto-inflammatory arthritis. Interleukin 6 (IL-6) and its receptor (IL-6R) play a role in the etiopathology of AS. The recent genome-wide association studies (GWASs) revealed that rs4129267; an intrinsic variant of IL6-R is associated with the risk of AS. We aimed to study the rs4129267 IL6R variant in Iranian AS patients and the correlation of this variant with the soluble interleukin-6 receptor (sIL-6R) serum level.

Materials and Methods:

In this case-control study, we genotyped rs4129267 IL6-R variant in extracted DNA from 498 AS patients and 495 matched healthy controls by Amplification-Refractory Mutation System Polymerase Chain Reaction (ARMS-PCR). The serum level of sIL-6R and IL-6 was also analysed in 39 controls and 42 AS patients by the ELISA method. The correlation between rs4129267 IL-6R variants and patients’ clinical manifestations and sIL-6R level was also investigated.

Results:

In comparison to the AS individuals, C allele were significantly less prevalent in the healthy control group (OR = 1.23 [1.01 –1.48], P value = .034). Patients had significantly elevated levels of IL-6 serum levels. There was a significant correlation between the presence of the rs4129267 T allele and increased sIL-6R level.

Conclusions:

Our study confirmed the significant association between the rs4129267 T variant and the protection against AS disease susceptibility. Increased IL-6 level and reduced frequency of sIL-6R rs4129267 T allele in patients which contributes to reduced sIL-6R serum level, highlights the significant role of IL-6 signalling pathway in AS pathogenesis.
Effectiveness of stem cell therapy for male infertility restoration: A systematic review
Authors: Modanlou Mohammad , Mahdipour Mahdi , Mobarak Halimeh
Published: November 2024

Cell therapy has emerged as a prominent leader in regenerative medicine, offering potential solutions for various disorders, including infertility. Half of all infertility cases are related to male factors. The objective of this study is to systematically summarize the existing knowledge regarding studies on stem cell-based therapy for the regeneration of impaired spermatogenesis. Initial searching was performed through main databases (e.g., PubMed, Scopus, Cochrane Library, and Embase) until December 2023. Articles conducted on stem cell transplantation into the testis of infertile models were considered. The titles and abstracts of articles were carefully evaluated and screened by independent authors. Nonrelated articles were deleted. The desired outcomes of infertility treatment after stem cell transplantation were attentively evaluated in the final selected articles. In the primary search, 3237 published studies were identified. Finally, 39 studies were included based on the eligibility criteria. In all studies except for two articles, all the outcomes considered, including germ cells/spermatogonia stem cell differentiation, spermatogenesis restoration, defective testicular tissue regeneration, improved sperm quality parameters, and hormonal levels, as well as increased expression of fertility-related markers and fertility rate, were observed after stem cell transplantation. Transplantation of stem cells, especially MSCs could be a safe and effective method for the treatment of male infertility patients, such as azoospermic cases. Further research to investigate the efficiency of different stem cell sources, providing nutrient conditions for the isolation and differentiation of stem cells, and exploring the paracrine effects of MSCs in male infertility therapy, could be useful.
Social support may buffer the effect of APOE ε4 allele on cognition in older adults
Authors: Payen Ameanté , Bateman James R , Dhanavanthri Muralidhara Sneha , Sachs Bonnie C , Cleveland Maryjo , Yang Mia , Lockhart Samuel N , Craft Suzanne , Bennett Jeanette M
Published: November 2024

Apolipoprotein E ( APOE) ε4 is a genetic risk factor for Alzheimer's disease (AD). Social support may confer protection against cognitive decline even in the presence of APOE ε4. We examined the relationship among APOE ε4 allele(s) carrier status, social support (overall and sub-sources), and cognition in 115 older adults (72.24 ± 8.29 years; 71.3% female). APOE ε4 carrier status moderated social support's effect on cognition, F(1, 106) = 5.08, p = 0.03, ΔR2 = 0.02. Among APOE ε4 carriers, as social support increased, cognitive functioning improved (β = 0.19, p = 0.03). This relationship was not found for APOE ε4 non-carriers, highlighting that socio-ecological influences may interact with genetic factors to influence later-life cognition.
A new bithiophene inhibited amyloid-β accumulation and enhanced cognitive function in the hippocampus of aluminum-induced Alzheimer's disease in adult rats
Authors: AbdElRaouf Kholoud , Farrag Hussein SH , El-Ganzuri Monir A , El-Sayed Wael M
Published: November 2024

Background

Alzheimer's disease (AD) is a progressive and irreversible neurological disorder that gradually deteriorates an individual's ability to carry out even the simplest tasks.

Objective

This study was undertaken to investigate the potential therapeutic efficacy of a novel bithiophene in a rat model of aluminum-induced AD pathology.

Methods

A total of 108 adult male albino rats weighing 160 ± 20 g, were randomly assigned to six groups: (1) a control group administered DMSO, (2) group receiving a high dose of bithiophene (1 mg/kg), (3) a model group received AlCl3 (100 mg/kg), those rats were then treated by either (4) bithiophene low dose (0.5 mg/kg), (5) high dose (1 mg/kg), or (6) memantine (20 mg/kg).

Results

Low dose bithiophene treatment was a promising strategy for mitigating oxidative stress and improving synaptic plasticity. This was demonstrated by reductions in malondialdehyde level, and increased activities of superoxide dismutase and catalase, and elevated glutathione content. Likewise, low dose bithiophene enhanced synaptic plasticity through a reduction in excitatory glutamate and norepinephrine levels, while increasing dopamine. Moreover, bithiophene significantly downregulated the expression of GSAP, GSK3- β, and p53, which are implicated in AD progression. This treatment also decreased caspase 3 and amyloid-β (Aβ1–42) accumulation in the hippocampus. Finally, behavioral assessments revealed that low dose bithiophene significantly enhanced learning abilities, as proved by Morris water maze.

Conclusions

Low dose bithiophene mitigated AD through ameliorating oxidative stress, promoting synaptic plasticity, inhibiting the Aβ accumulation, and enhancing the cognitive functions in a rat model.
Virtual reality interventions and their effects on the cognition of individuals with Alzheimer's disease: A systematic review and meta-analysis
Authors: Santos Vanessa Daudt , Costa Adriana Coelho , Junior Nelson Carvas , Delaere François Jean , Serlet Sebàstien , Dourado Marcia Cristina Nascimento
Published: November 2024

Background

Dementia due to Alzheimer's disease (AD) is the most prevalent neurocognitive disorder in the world and impacts the individual's cognitive functions and functionality in the early stages of the condition. Virtual reality (VR) interventions can assist in non-pharmacological treatment in a more ecological way, positively impacting cognitive abilities. However, there are few studies on VR exclusively involving people with AD in randomized controlled trials.

Objective

To evaluate the effects of VR intervention on the cognitive functions of people with AD.

Methods

A systematically conducted search was carried out in MEDLINE, EMBASE, BVS, Web of Science, and Scopus. Eligible studies were randomized controlled trials comparing the efficacy of VR and traditional cognitive interventions in people with AD. Methodologic quality was assessed with the Cochrane risk of bias tool, and outcomes were calculated as risk ratios (for dichotomous outcomes) and mean differences (for continuous outcomes) with 95% confidence interval.

Results

A total of three randomized controlled trials with 75 participants were included. An improvement in the performance of the VR group was observed in memory, especially when comparing the usual treatment [MD = 0.99; CI95%: 0.33; 1.66; I2 = 0%]. VR has little or no effect on participants’ executive function [MD = 1.36; 95%CI: −1.12; 3.85; I2 = 0%] compared to the usual treatment.

Conclusions

Our study results cautiously suggest, despite the small number of participants, that VR intervention may be a suitable memory treatment for individuals diagnosed with AD.
A Novel Approach for Monitoring Training Load and Wellness in Women’s College Gymnastics
Authors: Leupold Olivia , Cheng Jennifer , Wimberly Audrey , Nguyen Joseph , Tilley David , Gabbett Tim J. , Casey Ellen
Published: November 2024

Background:

Monitoring training load has the potential to improve sport performance and reduce injuries in athletes. This study examined training load and its association with wellness in artistic gymnastics.

Hypotheses:

Training load and changes in training load (acute:chronic workload ratio [ACWR]) vary throughout 1 season; wellness is inversely correlated with training load and ACWR.

Study Design:

Prospective case series.

Level of Evidence:

Level 3.

Methods:

A total of 30 female collegiate gymnasts from 4 Division I National Collegiate Athletic Association teams participated (mean age, 20 ± 2 years). During 4 months, before daily training, wellness surveys assessed sleep, energy, soreness, and mood (1-10; higher = better). After daily training, training load surveys assessed training duration per event (warm-up, vault, bars, beam, floor, strength and conditioning) and session rating of perceived exertion (RPE; 1-10; 10 = hardest) per event. Coaches reported technical complexity of training per event (1-4; 4 = hardest). Training load was calculated as [duration] × [RPE] × [technical complexity]. ACWR represented a ratio between acute [1-week] and chronic [4-week rolling average] training loads.

Results:

ACWR and weekly training load fluctuated throughout the season (ACWR mean weekly range: 0.68-1.11; training load mean weekly range: 2073-6193 arbitrary units). ACWR and weekly training loads were trichotomized into low, medium, and high groups; positive correlations were observed between each wellness variable and ACWR ( P < 0.01) and between each wellness variable and weekly training load ( P < 0.01).

Conclusion:

Our novel training load monitoring framework for women’s college gymnastics enabled us to characterize training load and its relationship with wellness throughout 1 season. This method should be explored in gymnasts across various ages and competitive levels.

Clinical Relevance:

This study proposes a framework and the initial findings of monitoring training load and wellness in collegiate women’s gymnastics.
A “food for special medical purposes” for the treatment of intestinal insufficiency/deficiency
Authors: Cava E. , Paolini B. , Martinelli B. , Anzolin F. , Pintus S. , Rahimi F. , Vincenzi M. , Bagnato C. , Lagattolla V. , Grandone I. , Carbonelli M.G.
Published: November 2024

Background:

Insufficient absorption of nutrients from food can be caused by impaired digestion, absorption or transport of nutrients, and can affect macronutrients, micronutrients, or both.

Objective:

The aim of this multicentric retrospective observational study is to confirm the efficacy of a formula (Bariatrifast, BIOITALIA S.r.l., Italy), supplementing vitamins and minerals, in patients with intestinal insufficiency from multiple different aetiologies, excluding bariatric surgery.

Methods:

A total of 78 patients were enrolled, assessing anthropometrics, blood pressure, and blood tests at baseline, 2, 4 and 6 months. Bariatrifast was the only supplement assumed. Mean age and BMI were 55.7 years and 23.4 kg/m2.

Results:

The study shows preliminary results of 20.6% and 52.9% of patients completing 6 and 4-month follow-up: increase of red blood cells and haemoglobin; a trend to increase over time for ferritin and iron; stable leukocytes, platelets and folate; a modest downward trend of transferrin; Vitamin-D improved remarkably then stabilized; mean values of heart rate and systolic-diastolic blood pressure remained stable. No undesirable effects were reported.

Conclusions:

In conclusion preliminary results suggest that using Bariatrifast in patients with intestinal insufficiency can improve the haematological panel, increasing Vitamins B12 and D, iron and ferritin, therefore confirming the efficacy of this special medical purpose food in intestinal insufficiency.
Knowledge, attitude, and diabetes self-care among individuals at high-risk of diabetes-related blindness in Bangladesh: a cross-sectional study
Authors: Pardhan Shahina , Islam Md. Saiful , Sapkota Raju
Published: November 2024

Background/Aim

Adequate knowledge, attitude, and self-care practice (KAP) are paramount in reducing diabetes complications. This study examined diabetes-related KAP in individuals who have been previously reported to be at a higher risk of blindness such as those on insulin treatment or with a longer (>6 years) duration of diabetes in Bangladesh.

Methods

Six hundred community-dwelling individuals (mean age = 52.7±11.6 years) who had been diagnosed with diabetes by their doctor were interviewed. A semi-structured questionnaire obtained self-reported information about diabetes-related KAP, duration, treatment of diabetes, and sociodemographic parameters including age, gender, and education level. Data were collected using a purposive sample technique and analyzed using Fischer’s exact test or independent samples t-tests.

Results

There were 271 males (45.2%) and 329 (54.8%) females. Of the total participants (mean diabetes duration = 6.6±6.2 years), 36.5% had diabetes for more than the median duration of 6 years, 80.7% were receiving insulin or insulin combined with tablets (insulin group) and the remaining 19.3% were on tablet only and/or diet control (non-insulin group). One-fifth (19.8%) of all the participants did not consider diabetes a serious disease, 31.3% were unaware that uncontrolled diabetes can cause blindness, 40.5% had never had their eyes tested for diabetic retinopathy and 41.5% stated that they would not attend diabetic retinopathy screening until their eyesight became worse. Among those in the insulin group, 42.1% reported being unaware that smoking may be harmful to diabetes compared to 30.2% of those in the non-insulin group (p= 0.02). Additionally, 64.7% of those in the insulin group were unaware that a diabetic retinal screening is different from a routine eye test for spectacles, compared to 44.8% in the non-insulin group (p< 0.001). Sixty-two percent of participants with diabetes duration of more than 6 years reported that diabetes management was a shared responsibility between the doctor and the patient compared to 48.3% with a shorter duration (p< 0.001). Those with a longer duration of diabetes (>6 years) also reported forgetting to take their medication more often than those with a shorter duration (p = 0.02). Twenty-one percent of participants with a duration of diabetes longer than six years had checked their eyes within the previous year compared to 63.5% of those with a shorter duration of diabetes (p< 0.001).

Conclusion

Individuals on insulin treatment demonstrated poorer knowledge and awareness of diabetes and diabetes eye screening. Those with a longer diabetes duration exhibited poorer self-care practices, particularly not taking the medication regularly, and neglecting diabetic retinal checkups. These issues need to be addressed in designing targeted educational interventions to prevent blindness from uncontrolled diabetes in the high-risk groups in Bangladesh.
Decolonization in sexual and reproductive health research methods: a scoping review
Authors: Stevens-Uninsky Maya , Barkhad Aisha , MacDonald Tonya , Perez Alexander , Mbuagbaw Lawrence
Published: November 2024

Background

As researchers and practitioners in the field of global health continue to acknowledge the ongoing impact of colonialism in their work, the call for decolonized research has increased. This has particular relevance in the field of sexual and reproductive health. Despite this recognized need, there is no singularly agreed upon definition of what it means to conduct decolonized research using decolonized methodologies. The aim of this review is to explore the approaches and methodologies used in contemporary sexual and reproductive health research aligned with decolonized systems of thinking.

Methods

This review was developed and conducted in accordance with the JBI and the Extension for Scoping Reviews (PRISMA-ScR) Checklist. In January 2023, Medline (Ovid), Embase, EMCare, Global Health Database, and Web of Science were systematically searched for relevant studies. Relevant grey literature was also scanned. The screening and data extraction were conducted by four independent reviewers using an iterative approach. The findings were analyzed to uncover shared characteristics between the studies.

Results

A total of 1775 articles were retrieved through our search strategy, of which 35 were included as discussing sexual health topics, and representing the principles of decolonization. Few of the included articles explicitly self-identified as decolonized literature. Common themes between studies included that most of the data collection was conducted in high-income countries, largely in North America, and the most prevalent sexual health topics were HIV/AIDs, and STIs/STDs. Most studies were qualitative, used community-based methodologies, and included some form of community advisory board.

Conclusions

This scoping review identifies shared characteristics of both successes and gaps in decolonized research that may inform the methodological processes of future researchers. It emphasizes the need for more decolonized research originating in low- and middle-income countries, as well as decolonization of quantitative research methodologies. The findings also emphasize the importance of community engagement throughout the research process. A shared definition of decolonization is necessary to codify this body of work. Future researchers should focus on clearly communicating their approach in the methodology so that it can be replicated and become part of a shared definition.

International Registered Report Identifier (IRRID): DERR1-10.2196/45771
Leaving the Norwegian opioid maintenance treatment program - patient experiences
Authors: Nesvåg Sverre , Bergqvist Per , Dahlberg Ingrid Elin , McKay James R.
Published: November 2024

Background

Opioid maintenance treatment (OMT) saves lives and makes it possible to start a process of health and social rehabilitation. Previous research shows that those who leave OMT after years of a drug free life and a reasonable level of health and social rehabilitation can have a good chance of living a stable drug free life after leaving the treatment. The aim of this study was to gain more knowledge about how patients who were in the process of leaving, or who had left OMT, experienced the leaving process.

Methods

The study was based on a thematic analysis of transcripts from individual in-depth interviews with 24 patients who had experience with leaving the Norwegian OMT program. Results: The participants in this study had a strong motivation to endure a demanding substitution medication tapering process and leave the OMT program. The tapering benefited strongly from adaptive routines based on ongoing dialog between patients and service providers throughout the process, based on individualized goals and patient experiences each step on the way. The participants had varied experiences regarding the quality and relevance of the support and meeting the need for further treatment and services.

Conclusions

Given a high level of rehabilitation and good support, this study shows that some OMT program patients are in a good position to successfully leave the OMT program or continue the substitution treatment on a low dosage in a less OMT program-dominated life.