bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Targeting the IL-1β pathway for cancer immunotherapy remodels the tumor microenvironment and enhances antitumor immune responses
Authors: Diwanji Rohan , O'Brien Neil A. , Choi Jiyoung E. , Nguyen Beverly , Laszewski Tyler , Grauel Angelo L. , Yan Zheng , Xu Xin , Wu Jincheng , Ruddy David A. , Piquet Michelle , Pelletier Marc R. , Savchenko Alexander , Charette LaSalette , Rodrik-Outmezguine Vanessa , Baum Jason , Millholland John M. , Wong Connie C. , Martin Anne-Marie , Dranoff Glenn , Pruteanu-Malinici Iulian , Cremasco Viviana , Sabatos-Peyron Catherine , Jayaraman Pushpa
Published: September 2024

Abstract
High levels of IL-1β can result in chronic inflammation, which in turn can promote tumor growth and metastasis. Inhibition of IL-1β could therefore be a promising therapeutic option in the treatment of cancer. Here, the effects of IL-1β blockade induced by the monoclonal antibodies canakinumab and gevokizumab were evaluated alone or in combination with docetaxel, anti-PD-1, anti-VEGFα and anti-TGFβ treatment in syngeneic and humanized mouse models of cancers of different origin. Canakinumab and gevokizumab did not show notable efficacy as single-agent therapies; however, IL-1β blockade enhanced the effectiveness of docetaxel and anti–PD-1. Accompanying these effects, blockade of IL-1β alone or in combination induced significant remodeling of the tumor microenvironment (TME), with decreased numbers of immune suppressive cells and increased tumor infiltration by dendritic cells and effector T cells. Further investigation revealed that cancer-associated fibroblasts (CAFs) were the cell type most affected by treatment with canakinumab or gevokizumab in terms of change in gene expression. IL-1β inhibition drove phenotypic changes in CAF populations, particularly those with the ability to influence immune cell recruitment. These results suggest that the observed remodeling of the TME following IL-1β blockade may stem from changes in CAF populations. Overall, the results presented here support the potential use of IL-1β inhibition in cancer treatment. Further exploration in ongoing clinical studies will help identify the best combination partners for different cancer types, cancer stages and lines of treatment.
Data from IL12/18/21 pre-activation enhances the anti-tumor efficacy of expanded γδT cells and overcomes resistance to anti-PD-L1 treatment
Authors: Teo Huey Yee , Song Yuan , Yong Kylie Su Mei , Liu Yonghao , Mei Yu , Hanafi Zuhairah Binte. , Zhu Ying , Chua Yen Leong , Gascoigne Nicholas R.J. , Chen Qingfeng , Liu Haiyan
Published: September 2024

Abstract
γδT cells are promising candidates for cellular immunotherapy due to their immune regulation through cytokine production and MHC-independent direct cytotoxicity against a broad spectrum of tumors. However, current γδT cell-based cancer immunotherapy has limited efficacy, and novel strategies are needed to improve clinical outcomes. Here, we report that cytokine pre-treatment with IL12/18, IL12/15/18, IL12/18/21, and IL12/15/18/21 effectively enhanced the activation and cytotoxicity of in vitro-expanded murine and human γδT cells. However, only adoptive transfer of IL12/18/21 pre-activated γδT cells significantly inhibited tumor growth in a murine melanoma model and a hepatocellular carcinoma model. Both IL12/18/21 pre-activated antibody-expanded and zoledronate-expanded human γδT cells effectively controlled tumor growth in a humanized mouse model. IL12/18/21 pre-activation promoted γδT cell proliferation and cytokine production in vivo and enhanced IFNγ production and activation of endogenous CD8+ T cells in a cell-cell contact- and ICAM-1-dependent manner. Furthermore, the adoptive transfer of IL12/18/21 pre-activated γδT cells could overcome the resistance to anti-PD-L1 therapy, and the combination therapy had a synergistic effect on the therapeutic outcomes. Moreover, the enhanced anti-tumor function of adoptively transferred IL12/18/21 pre-activated γδT cells was largely diminished in the absence of endogenous CD8+ T cells when administered alone or in combination with anti-PD-L1, suggesting a CD8+ T cell-dependent mechanism. Taken together, IL12/18/21 pre-activation can promote γδT cell anti-tumor function and overcome the resistance to checkpoint blockade therapy, indicating an effective combinational cancer immunotherapeutic strategy.
Data from T cell–mediated development of stromal fibroblasts with an immune-enhancing chemokine profile
Authors: Yan Ran , Moresco Philip , Gegenhuber Bruno , Fearon Douglas T.
Published: September 2024

Abstract
Stromal fibroblasts reside in inflammatory tissues that are characterized by either immune suppression or activation. Whether and how fibroblasts adapt to these contrasting microenvironments remains unknown. Cancer-associated fibroblasts (CAFs) mediate immune quiescence by producing the chemokine CXCL12, which coats cancer cells to suppress T-cell infiltration. We examined whether CAFs can also adopt an immune-promoting chemokine profile. Single-cell RNA-sequencing of CAFs from mouse pancreatic adenocarcinomas identified a sub-population of CAFs with decreased expression of Cxcl12 and increased expression of the T cell-attracting chemokine Cxcl9 in association with T-cell infiltration. TNFα and IFNγ containing conditioned media from activated CD8+ T cells converted stromal fibroblasts from a CXCL12+/CXCL9– immune suppressive phenotype into a CXCL12–/CXCL9+ immune-activating phenotype. Recombinant IFNγ and TNFα acted together to augment CXCL9 expression, whereas TNFα alone suppressed CXCL12 expression. This coordinated chemokine switch led to increased T-cell infiltration in an in vitro chemotaxis assay. Our study demonstrates that CAFs have a phenotypic plasticity that allows their adaptation to contrasting immune tissue microenvironments.
Data from Systemic Alterations in Type-2 Conventional Dendritic Cells Leads to Impaired Tumor Immunity in Pancreatic Cancer
Authors: James C. Alston. , Baer John M. , Zuo Chong , Panni Usman Y. , Knolhoff Brett L. , Hogg Graham D. , Kingston Natalie L. , Kang Liang-I , Lander Varintra E. , Luo Jingqin , Tao Yu , Watson Mark A. , Aft Rebecca , Fields Ryan C. , Hawkins William G. , DeNardo David G.
Published: September 2024

Abstract
Intratumoral T-cell dysfunction is a hallmark of pancreatic tumors, and efforts to improve dendritic cell (DC)-mediated T-cell activation may be critical in treating these immune therapy unresponsive tumors. Recent evidence indicates that mechanisms that induce dysfunction of type 1 conventional DCs (cDC1) in pancreatic adenocarcinomas (PDACs) are drivers of the lack of responsiveness to checkpoint immunotherapy. However, the impact of PDAC on systemic type 2 conventional DC (cDC2) development and function has not been well studied. Herein, we report the analysis of 3 cohorts, totaling 106 samples, of human blood and bone marrow (BM) from PDAC patients for changes in cDCs. We found circulating cDC2s and their progenitors were significantly decreased in the blood of PDAC patients, and repressed numbers of cDC2s were associated with poor prognosis. Serum cytokine analyses identified IL6 as significantly elevated in PDAC patents and negatively correlated with cDC numbers. In vitro, IL6 impaired the differentiation of cDC1s and cDC2s from BM progenitors. Single-cell RNA sequencing analysis of human cDC progenitors in the BM and blood of PDAC patients showed an upregulation of the IL6/STAT3 pathway and a corresponding impairment of antigen processing and presentation. These results suggested that cDC2s were systemically suppressed by inflammatory cytokines, which was linked to impaired antitumor immunity.
Data from Aerobic exercise alters the melanoma microenvironment and modulates ERK5 S496 phosphorylation
Authors: Savage Hannah , Pareek Sumedha , Lee Jonghae , Ballarò Riccardo , Conterno Minussi Darlan , Hayek Karma , Sadullozoda Mumina , Lochmann Brooke S. , McQuade Jennifer L. , LaVoy Emily C. , Marmonti Enrica , Patel Hetal , Wang Guangyu , Imanishi Masaki , Kotla Sivareddy , Abe Jun-ichi , Schadler Keri L.
Published: September 2024

Abstract
Exercise changes the tumor microenvironment by remodeling blood vessels and increasing infiltration by cytotoxic immune cells. The mechanisms driving these changes remain unclear. Herein, we demonstrate that exercise normalizes tumor vasculature and upregulates endothelial expression of VCAM1 in YUMMER 1.7 and B16F10 murine models of melanoma but differentially regulates tumor growth, hypoxia, and the immune response. We found that exercise suppressed tumor growth and increased CD8+ T-cell infiltration in YUMMER but not in B16F10 tumors. Single-cell RNA sequencing and flow cytometry revealed exercise modulated the number and phenotype of tumor-infiltrating CD8+ T cells and myeloid cells. Specifically, exercise caused a phenotypic shift in the tumor-associated macrophage population and increased the expression of major histocompatibility complex class II transcripts. We further demonstrated that ERK5 S496A knock-in mice, which are phosphorylation deficient at the S496 residue, ‘mimicked’ the exercise effect when unexercised, yet when exercised, these mice displayed a reversal in the effect of exercise on tumor growth and macrophage polarization compared to wild-type mice. Taken together, our results reveal tumor-specific differences in the immune response to exercise and show that ERK5 signaling via the S496 residue plays a crucial role in exercise-induced tumor microenvironment changes.  
Data from Ncoa2 promotes CD8+ T cell-mediated anti-tumor immunity by stimulating T-cell activation via upregulation of PGC-1α critical for mitochondrial function
Authors: Zhong Xiancai , Wu Hongmin , Ouyang Ching , Zhang Wencan , Shi Yun , Wang Yi-Chang , Ann David K. , Gwack Yousang , Shang Weirong , Sun Zuoming
Published: September 2024

Abstract
Nuclear receptor coactivator 2 (Ncoa2) is a member of the Ncoa family of co-activators, and we previously showed that Ncoa2 regulates the differentiation of induced regulatory T cells. However, it remains unknown if Ncoa2 plays a role in CD8+ T-cell function. Here, we show that Ncoa2 promotes CD8+ T cell-mediated immune responses against tumors by stimulating T-cell activation via upregulating PGC-1α expression to enhance mitochondrial function. Mice deficient in Ncoa2 in T cells (Ncoa2fl/fl/CD4Cre) displayed defective immune responses against implanted MC38 tumors, which associated with significantly reduced tumor-infiltrating CD8+ T cells and decreased IFNγ production. Consistently, CD8+ T cells from Ncoa2fl/fl/CD4Cre mice failed to reject tumors after adoptive transfer into Rag1-/- mice. Further, in response to TCR stimulation, Ncoa2fl/fl/CD4Cre CD8+ T cells failed to increase mitochondrial mass, showed impaired oxidative phosphorylation, and had lower expression of PGC-1α, a master regulator of mitochondrial biogenesis and function. Mechanically, T cell activation-induced phosphorylation of CREB triggered the recruitment of Ncoa2 to bind to enhancers, thus, stimulating PGC-1α expression. Forced expression of PGC-1α in Ncoa2fl/fl/CD4Cre CD8+ T cells restored mitochondrial function, T-cell activation, IFNγ production, and anti-tumor immunity. This work informs the development of Ncoa2-based therapies that modulate CD8+ T cell-mediated anti-tumor immune responses.
Supplementary Data 1 from Molecular evolution of classic Hodgkin lymphoma revealed through whole genome sequencing of Hodgkin and Reed Sternberg cells
Authors: Maura Francesco , Ziccheddu Bachisio , Xiang Jenny Z. , Bhinder Bhavneet , Rosiene Joel , Abascal Federico , Maclachlan Kylee H. , Eng Kenneth Wha. , Uppal Manik , He Feng , Zhang Wei , Gao Qi , Yellapantula Venkata D. , Trujillo-Alonso Vicenta , Park Sunita I. , Oberley Matthew J. , Ruckdeschel Elizabeth , Lim Megan S. , Wertheim Gerald B. , Barth Matthew J. , Horton Terzah M. , Derkach Andriy , Kovach Alexandra E. , Forlenza Christopher J. , Zhang Yanming , Landgren Ola , Moskowitz Craig H. , Cesarman Ethel , Imielinski Marcin , Elemento Olivier , Roshal Mikhail , Giulino-Roth Lisa
Published: September 2024

R code of our analysis for driver mutation discovery in Hodgkin lymphoma WGS and WES.
Supplementary Table S9 from In vivo screening unveils pervasive RNA-binding protein dependencies in leukemic stem cells and identifies ELAVL1 as a therapeutic target
Authors: Vujovic Ana , de Rooij Laura , Keyvani Chahi Ava , Chen He Tian , Yee Brian A. , Loganathan Sampath K. , Liu Lina , Chan Derek C. H. , Tajik Amanda , Tsao Emily , Moreira Steven , Joshi Pratik , Xu Joshua , Wong Nicholas , Balde Zaldy , Jahangiri Soheil , Zandi Sasan , Aigner Stefan , Dick John E. , Minden Mark D. , Schramek Daniel , Yeo Gene W. , Hope Kristin J.
Published: September 2024

Table S9 shows the (a) differentially expressed transcripts and (b) altered pathways as identified by GSEA from the ELAVL1 knockdown human primary AML RNA-sequencing data set.
Supplementary Table S8 from In vivo screening unveils pervasive RNA-binding protein dependencies in leukemic stem cells and identifies ELAVL1 as a therapeutic target
Authors: Vujovic Ana , de Rooij Laura , Keyvani Chahi Ava , Chen He Tian , Yee Brian A. , Loganathan Sampath K. , Liu Lina , Chan Derek C. H. , Tajik Amanda , Tsao Emily , Moreira Steven , Joshi Pratik , Xu Joshua , Wong Nicholas , Balde Zaldy , Jahangiri Soheil , Zandi Sasan , Aigner Stefan , Dick John E. , Minden Mark D. , Schramek Daniel , Yeo Gene W. , Hope Kristin J.
Published: September 2024

Table S8 shows transcripts from the ELAVL1 knockout RNA-sequencing data set that are (a) alternatively spliced and (b) alternatively spliced as well as bound by ELAVL1 as identified by eCLIP-sequencing.
Supplementary Figure S3 from In vivo screening unveils pervasive RNA-binding protein dependencies in leukemic stem cells and identifies ELAVL1 as a therapeutic target
Authors: Vujovic Ana , de Rooij Laura , Keyvani Chahi Ava , Chen He Tian , Yee Brian A. , Loganathan Sampath K. , Liu Lina , Chan Derek C. H. , Tajik Amanda , Tsao Emily , Moreira Steven , Joshi Pratik , Xu Joshua , Wong Nicholas , Balde Zaldy , Jahangiri Soheil , Zandi Sasan , Aigner Stefan , Dick John E. , Minden Mark D. , Schramek Daniel , Yeo Gene W. , Hope Kristin J.
Published: September 2024

Supplemental Figure S3 shows the generation of the bcCML mouse model and the effects of ELAVL1 on normal bone marrow in vivo.
Supplementary Figure S2 from In vivo screening unveils pervasive RNA-binding protein dependencies in leukemic stem cells and identifies ELAVL1 as a therapeutic target
Authors: Vujovic Ana , de Rooij Laura , Keyvani Chahi Ava , Chen He Tian , Yee Brian A. , Loganathan Sampath K. , Liu Lina , Chan Derek C. H. , Tajik Amanda , Tsao Emily , Moreira Steven , Joshi Pratik , Xu Joshua , Wong Nicholas , Balde Zaldy , Jahangiri Soheil , Zandi Sasan , Aigner Stefan , Dick John E. , Minden Mark D. , Schramek Daniel , Yeo Gene W. , Hope Kristin J.
Published: September 2024

Supplemental Figure S2 shows validation of sgRNA -mediated knockout of hit RBPs, comparison of hit RBP depletion in RN2c in vitro versus in vivo, effects of ELAVL1 loss on human AML cell lines, characteristics of the MLL-AF9 AML mouse model, and ELAVL1 expression in normal hematopoietic cells.
Supplementary Table S4 from The polyamine-hypusine circuit controls an oncogenic translational program essential for malignant conversion in MYC-driven lymphoma
Authors: Nakanishi Shima , Li Jiannong , Berglund Anders E. , Kim Youngchul , Zhang Yonghong , Zhang Ling , Yang Chunying , Song Jinming , Mirmira Raghavendra G. , Cleveland John L.
Published: September 2024

Supplementary Table S4 lists oncogenes and tumor suppressor genes analyzed for changes in translation efficiency (TE) following depletion of eIF5A or DHPS, related to Fig. 5E.
Supplementary Table S3 from The polyamine-hypusine circuit controls an oncogenic translational program essential for malignant conversion in MYC-driven lymphoma
Authors: Nakanishi Shima , Li Jiannong , Berglund Anders E. , Kim Youngchul , Zhang Yonghong , Zhang Ling , Yang Chunying , Song Jinming , Mirmira Raghavendra G. , Cleveland John L.
Published: September 2024

Supplementary Table S3 lists 665 shared differentially translated transcripts (DTT) identified following depletion of eIF5A or DHPS, related to Fig. 5C.
Supplementary Protocol from A phase Ib/II study of ivosidenib with venetoclax +/- azacitidine in IDH1-mutated myeloid malignancies
Authors: Lachowiez Curtis A. , Loghavi Sanam , Zeng Zhihong , Tanaka Tomoyuki , Kim Yi June , Uryu Hidetaka , Turkalj Sven , Jakobsen Niels Asger , Luskin Marlise R. , Duose Dzifa Y. , Tidwell Rebecca S S. , Short Nicholas J. , Borthakur Gautam , Kadia Tapan M. , Masarova Lucia , Tippett George D. , Bose Prithviraj , Jabbour Elias J. , Ravandi Farhad , Daver Naval G. , Garcia-Manero Guillermo , Kantarjian Hagop , Garcia Jacqueline S. , Vyas Paresh , Takahashi Koichi , Konopleva Marina , DiNardo Courtney D.
Published: September 2024

Supplementary protocol for "Phase Ib/II Investigator Initiated Study of the IDH1-mutant inhibitor ivosidenib (AG120) with the BCL2 inhibitor venetoclax +/- azacitidine in IDH1-mutated hematologic malignancies"
Table S2 from HTLV-1 bZIP factor-induced reprogramming of lactate metabolism and epigenetic status promote leukemic cell expansion
Authors: Toyoda Kosuke , Yasunaga Jun-ichirou , Shichijo Takafumi , Arima Yuichiro , Tsujita Kenichi , Tanaka Azusa , Salah Tarig , Zhang Wenyi , Hussein Osama , Sonoda Miyu , Watanabe Miho , Kurita Daisuke , Nakashima Kazutaka , Yamada Kyohei , Miyoshi Hiroaki , Ohshima Koichi , Matsuoka Masao
Published: September 2024

Mouse cluster 2 genes whose H3K27me3 in TSS’s was decreased.
Figure S5 from HTLV-1 bZIP factor-induced reprogramming of lactate metabolism and epigenetic status promote leukemic cell expansion
Authors: Toyoda Kosuke , Yasunaga Jun-ichirou , Shichijo Takafumi , Arima Yuichiro , Tsujita Kenichi , Tanaka Azusa , Salah Tarig , Zhang Wenyi , Hussein Osama , Sonoda Miyu , Watanabe Miho , Kurita Daisuke , Nakashima Kazutaka , Yamada Kyohei , Miyoshi Hiroaki , Ohshima Koichi , Matsuoka Masao
Published: September 2024

Transcriptional regulation of SLC16A1 and SLC16A3 by TAp73, and mRNA expression levels of MCT-coding genes among various cancers.
Table S5 from Time-dependent prognostic value of serological and measurable residual disease assessments after idecabtagene vicleucel
Authors: Paiva Bruno , Manrique Irene , Rytlewski Julie , Campbell Timothy , Kazanecki Christian C. , Martin Nathan , Anderson Larry D. , Berdeja Jesus G. , Lonial Sagar , Raje Noopur S. , Lin Yi , Moreau Philippe , San-Miguel Jesus F. , Munshi Nikhil C. , Kaiser Shari
Published: September 2024

number samples with inferior limit of MRD
Table S3 from Time-dependent prognostic value of serological and measurable residual disease assessments after idecabtagene vicleucel
Authors: Paiva Bruno , Manrique Irene , Rytlewski Julie , Campbell Timothy , Kazanecki Christian C. , Martin Nathan , Anderson Larry D. , Berdeja Jesus G. , Lonial Sagar , Raje Noopur S. , Lin Yi , Moreau Philippe , San-Miguel Jesus F. , Munshi Nikhil C. , Kaiser Shari
Published: September 2024

CR and MRD on treated population
Supplementary Materials and Methods from Synergistic Effects of PARP Inhibition and Cholesterol Biosynthesis Pathway Modulation
Authors: Rutkowska Anna , Eberl H. Christian , Werner Thilo , Hennrich Marco L. , Sévin Daniel C. , Petretich Massimo , Reddington James P. , Pocha Shirin , Gade Stephan , Martinez-Segura Amalia , Dvornikov Dmytro , Karpiak Joel , Sweetman Gavain M.A. , Fufezan Christian , Duempelfeld Birgit , Braun Florian , Schofield Christopher , Keles Hakan , Alvarado David , Wang Zhuo , Jansson Keith H. , Faelth-Savitski Maria , Curry Edward , Remlinger Katja , Stronach Euan A. , Feng Bin , Sharma Geeta , Coleman Kevin , Grandi Paola , Bantscheff Marcus , Bergamini Giovanna
Published: September 2024

Supplementary Materials and Methods
Figure S3 from Synergistic Effects of PARP Inhibition and Cholesterol Biosynthesis Pathway Modulation
Authors: Rutkowska Anna , Eberl H. Christian , Werner Thilo , Hennrich Marco L. , Sévin Daniel C. , Petretich Massimo , Reddington James P. , Pocha Shirin , Gade Stephan , Martinez-Segura Amalia , Dvornikov Dmytro , Karpiak Joel , Sweetman Gavain M.A. , Fufezan Christian , Duempelfeld Birgit , Braun Florian , Schofield Christopher , Keles Hakan , Alvarado David , Wang Zhuo , Jansson Keith H. , Faelth-Savitski Maria , Curry Edward , Remlinger Katja , Stronach Euan A. , Feng Bin , Sharma Geeta , Coleman Kevin , Grandi Paola , Bantscheff Marcus , Bergamini Giovanna
Published: September 2024

Niraparib specific modulation of cholesterol biosynthesis pathway in cancer cell lines
Figure 1 from Synergistic Effects of PARP Inhibition and Cholesterol Biosynthesis Pathway Modulation
Authors: Rutkowska Anna , Eberl H. Christian , Werner Thilo , Hennrich Marco L. , Sévin Daniel C. , Petretich Massimo , Reddington James P. , Pocha Shirin , Gade Stephan , Martinez-Segura Amalia , Dvornikov Dmytro , Karpiak Joel , Sweetman Gavain M.A. , Fufezan Christian , Duempelfeld Birgit , Braun Florian , Schofield Christopher , Keles Hakan , Alvarado David , Wang Zhuo , Jansson Keith H. , Faelth-Savitski Maria , Curry Edward , Remlinger Katja , Stronach Euan A. , Feng Bin , Sharma Geeta , Coleman Kevin , Grandi Paola , Bantscheff Marcus , Bergamini Giovanna
Published: September 2024

Comprehensive selectivity profile of PARP inhibitors. A, Selectivity profiling of talazoparib, olaparib, and niraparib on a PARP selective bead matrix using affinity enrichment chemoproteomics from MDA-MB-231 lysate. Identified targets with their respective mean (n = 3) apparent dissociation constants pKdapp are visualized on a phylogenetic tree of the PARP family (details and statistical analysis in Supplementary Table S1). B, Representative dose–response curves for PARP1 and PARP2 derived from A. C, Quantitative target engagement of PARP1 and PARP2 by olaparib and niraparib (30, 3.75, 0.468, 0.058, 0.007, 0.0009, and 00001 μmol/L) determined by thermal proteome profiling in UWB1.289 cells at 48°C (n = 3, details and statistical analysis in Supplementary Table S2). D, Selectivity profiling of talazoparib, olaparib, and niraparib on a kinase selective bead matrix from a lysate mix. Identified targets (n = 2, details in Supplementary Table S3) for niraparib are visualized on a phylogenetic tree of the kinase family. No kinases were identified for olaparib and talazoparib under the chosen conditions. E, Two-dimensional thermal proteome profiling (2D-TPP) in UWB1.289 cells to identify targets and off-targets of niraparib (n = 1). Heat maps display relative stabilization compared with the control treatment. Dependencies on compound concentration (x-axis: 30, 6, 0.85714, and 0.12245 μmol/L) and temperature (y-axis: 42°C–63.9°C) are visualized. F, Heatmap visualization (enlarged from E) and dose–response curve (at 50.4°C) of thermal stabilization of lanosterol synthase (LSS).
Motor Function Is Associated with Cerebral Small Vessel Disease and Can Predict Mortality and Poor Functional Outcome
Authors: Hosoya Megumi , Toi Sono , Seki Misa , Hoshino Takao , Sato Yasuto , Yoshizawa Hiroshi , Iijima Mutsumi , Kitagawa Kazuo
Published: September 2024

Introduction: The primary objective of this study was to elucidate the predictive role of subtle motor impairment evaluated using the Unified Parkinson’s Disease Rating Scale (UPDRS) Part III on mortality and functional outcome. The secondary objective was to evaluate the association of motor impairment with small vessel disease (SVD) severity. Methods: We derived data from a Japanese cohort of patients with evidence of SVD who were enrolled from 2015 to 2019, and followed until 2023. The present study included 586 participants who agreed for UPDRS Part III evaluation. The severity of white matter hyperintensities (WMHs) and the presence of lacunes were evaluated. Cox proportional hazard models and multiple logistic regression analysis were used to examine the association between UPDRS Part III score and all-cause death and functional outcome defined by the modified Rankin Scale (mRS) score at the last visit, respectively. Results: The median age was 71 years, and the median UPDRS Part III score was 2. The UPDRS Part III score was associated with the severity of WMH (r = 0.225, p < 0.001) and the number (0, 1, ≥2) of lacunes (p < 0.001). During a mean follow-up period of 4.8 years, 29 patients died. The Cox proportional hazard analysis revealed that high UPDRS Part III scores (≥5) were associated with a higher risk of all-cause death compared to low (score 0) and middle (score 1–4) scores (adjusted hazard ratio 3.04; 95% confidence interval, 1.50–7.34, p = 0.005). In multivariate logistic analysis, high UPDRS Part III scores were associated with poor functional outcome (mRS of ≥3) compared with low and middle scores after adjusting for confounding factors (adjusted odds ratio 1.86; 95% confidence interval 1.02–3.41, p = 0.043). Conclusions: Subtle motor impairment was associated with the severity of WMH and number of lacunes and could predict mortality and poor functional outcome independently of vascular risk factors and severity of WMH and lacunes.
Lung Tensioning Device Coil Treatment in Patients with Severe Emphysema: A Prospective Safety and Feasibility Trial (EFFORT)
Authors: Roodenburg Sharyn A. , Klooster Karin , Hartman Jorine E. , Kontogianni Konstantina , Brock Judith M. , Dittrich A. Susanne , van Dijk Marlies , Koster T. David , Herth Felix J.F. , Slebos Dirk-Jan
Published: September 2024

Introduction: Currently, there is a lack of bronchoscopic lung volume reduction options that do not depend on fissure integrity. Endobronchial coils have been extensively studied to address this need but exhibited variable patient response and have been discontinued. Lung tension device (LTD) coils represent the next-generation coil treatment. This study aimed to evaluate safety, feasibility, and efficacy of LTD-coil treatment. Methods: Patients with advanced emphysema and hyperinflation were enrolled at two European sites. LTD-coils (Free Flow Medical, Fremont, CA, USA) were implanted in the two most destructed lobes, as determined by quantitative CT analysis, in two separate procedures. The primary endpoint was 3-month follow-up after the last treatment. Results: Fourteen patients (50% male, median age 64 years, FEV1 23%predicted, RV 249%predicted) received LTD-coil treatment: 12 received bilateral and 2 unilateral treatment. Six serious respiratory adverse events occurred within the initial 3 months posttreatment, including one device-associated death. Treatment significantly reduced in- and expiratory volume of the treated lobes (−410 [−710, −340], p = 0.004 and −650 [−730, −190] mL, p < 0.001, respectively) and improved quality of life (SGRQ total score −4.6 [−21.0, −2.6], p < 0.001). However, at a group level, no significant improvements in pulmonary function or 6-min walk distance were observed. Responder rates ranged from 18% to 54% for the different endpoints. Conclusion: This first-in-human study shows that the new LTD-coil procedure is feasible with a safety profile comparable to the previous coil treatment. While the treatment effectively reduced lobar volume and modestly improved quality of life up to 3 months’ follow-up, at a group level it did not significantly enhance pulmonary function or exercise capacity.
Social Cognition and Social Context: a New Reading of the Scientific Heritage of G.M. Andreeva
Authors: Khoroshilov Dmitry A.
Published: September 2024

Background. Studying the reception of the scientific heritage of G.M. Andreeva in social psychology and related disciplines is relevant due to the increasing attention to the psychology of uncertainty and transitive society. This attention is the result of the historical process of modernization, understood as a crisis transition from a traditional way of thinking and life to a modern one. Objective. The purpose of the article is to show the heuristic nature of the ideas proposed by G.M. Andreeva in modern psychology as well as to identify new directions for the study of social cognition as a process of constructing an image of the social world in a situation of social transformations. Study Participants. A meta-analysis of theoretical and empirical studies based on the approach of G.M. Andreeva is carried out. The sample was made up of representatives of various social groups of Russian society, which allows us to draw conclusions about the structure of the image of the world, constructed in everyday and mass consciousness under the influence of radical social transformations. Methods. Methods of historical and psychological hermeneutics and comparative analysis are used, as well as a complex of qualitative research methods. Results. The epistemological and conceptual principles of G.M. Andreeva’s scientific school of social psychology are revealed. These principles focus on the problems of social cognition. The ways of conceptualizing the social context (lifeworld, life space, social institutions) and the units of its description and analysis (cognitive, affective and behavioral) are highlighted. The system of categories for psychological analysis of contexts presented in the article (image of the social world — collective emotions — coping strategies) allows us to study the phenomenology and mechanisms of social cognition in a changing transitive society, as well as to set directions for further research on the topic. Conclusions. The relevance of the ideas and scientific forecasts of G.M. Andreeva has been proven. The ideas have received empirical confirmation in modern interdisciplinary research and provide a solid theoretical and methodological basis for the psychological understanding and explanation of social change.
Identification with the Generation: Socio-Psychological Approach and Empirical Research Experience
Authors: Belinskaya Elena P. , Rikel Alexander M.
Published: September 2024

Background. The relevance of the study is determined by two core factors. (1) In conditions of uncertainty and reduction of the usual bases of social solidarity, the analysis of the patterns of generational identity sets a new perspective for understanding the dynamic unity of the processes of constructing social and personal identities. (2) Identifying the phenomenology of identity of different generations seems necessary for the needs of practical psychological assistance to various social subjects. Objective. The research is focused on revealing and describing the features of identification with the generational group in people belonging to different generations. Methods. Author's questionnaire (Appendix 1) consisting of: (1) questions about historical events that influenced the formation of a generational group; (2) questions about the cultural life scenario of a generation and an assessment of the probability of a particular typical event; (3) unfinished sentences on the psychological portrait of one's generation. Study Participants. 215 respondents (Generations of Stagnation, Reform, Millennials, and Zoomers) took part in the research. Results. The identity portrait of the stagnation generation includes: an emphasis on large-scale events; the prevalence of collectivist and family values; self-attribution of such qualities as patriotism, openness to the world, conscientiousness, responsiveness. The identity of the reform generation is based on the events of the 1990s, interpreting them through the prism of the policy of openness to the outside world, as well as technological events; it is “transitional” in terms of typical life scenarios and personality traits. The identity portrait of millennials includes: mainly the events of the 2010s and economic events, the prevalence of the values of freedom, creativity, progress; self-attribution of experiencing life's difficulties. The identity of the zoomer generation is significantly different: they do not have political events in their identity portrait; recent events (pandemic, digitalization) act as an identification support; marriage and childbirth are unlikely in life scenarios; self-attributions include flexibility, individualism, political correctness, and peacefulness. Conclusion. The socio-psychological analysis of the identity of generations is implemented at three interconnected levels through identification: with historical events, with events of the life scenario and with a typical psychological portrait of a representative of the generation.
Moral Decision-Making in Situations of Potential Cyberbullying in Relation to Individual Psychological Characteristics of Students
Authors: Pogozhina Irina N. , Rekun Olga S.
Published: September 2024

Background. The Internet environment creates a special reality for communication, in which socially accepted systems of norms and values are often no longer valid. In conflict situations, the anonymity of Internet communication may reduce the degree of personal moral responsibility for the “digital deeds” and lead to the choice of unethical ways of behaviour, which include cyberbullying. Highlighting the system of cognitive and personal factors involved in the regulation of the moral orientation of behaviour in online communication is an urgent scientific task. Objective. The aim is to explore the regulation of moral orientation in decision-making in situations containing possibility of cyberbullying. The following psychological features of students are considered: the level of moral development, the level of communicative skill development, the perception of cyberbullying as a phenomenon. Study Participants. The sample included 85 respondents of varying ages, ranging from 18 to 26 years old (M = 21; SD = 1.8). Methods. The study engaged the following materials: the “Justice-Care” technique by S.V. Molchanov; communication skills test by L. Michelson (adapted by Yu.Z. Gilbukh); authors' techniques “Open questions” and “Case-method” applied for identifying the content of ideas about cyberbullying and orientation of decision-making (ethical/unethical) in situations of potential cyberbullying. Results. A significant positive correlation (ρ-Spearman; p < 0.05) was found between the ethical choice of decisions in situations of potential cyberbullying, subscales of moral development (“Self-sacrifice”, “Self-respect”) and the content of ideas about cyberbullying. Moreover, significant negative correlations (ρ-Spearman; p < 0.05) were identified between the unethical choices in the investigated situations, subscale of “Preconventional” level of moral development, and communication skills. Conclusions. The moral orientation of the decisions we make in situations of potential cyberbullying is significantly related to the following individual psychological features of students: (1) students who often choose ethical decisions have fully formed ideas about cyberbullying as a phenomenon, they do not prioritize their own interests and consider the values of others; (2) students who choose unethical decisions have low level of development of communication skills, look for personal gain in communication and less often consider the values of other people.
From Recession to Pandemic
Authors: Aref Fariborz
Published: September 2024

Embarking on an exploration of socio-economic disparities within OECD countries over two decades, this research investigates the effects of the Great Recession and the COVID-19 pandemic on income distribution, labor market dynamics, and health outcomes. Using Exploratory Data Analysis of time-series and mixed-effects models, the study reveals a context characterized by intensifying inequalities, with variations reflecting the unique socio-economic structures of individual countries. It uncovers a pronounced increase in income inequality in countries including Lithuania, Luxembourg, Italy, and the United States, alongside shifts in labor market conditions, with the United States being particularly notable. Furthermore, the analysis highlights a widening of health disparities, evidenced by a decline in life expectancy in countries like the United States, Poland, and Slovakia, and a slowdown in reducing infant mortality rates. The use of mixed-effects models elucidates the role of country-specific factors in shaping these inequalities, revealing a complex interplay of influences that highlight the varied impacts of the pandemic across the OECD. This study not only charts the evolving contours of socio-economic inequalities but also enhances the understanding of global crises’ effects on developed economies.
1. The pogroms in Poland, 1935–37
Authors: Leshchinsky Yankev
Published: September 2024

In this chapter, Leshchinsky compares the 1935-37 Polish pogroms with the 1881-1917 Russian pogroms and the 1918-21 Ukrainian pogroms in terms of their support base, political context, level of violence, and objectives. He finds that the Polish pogroms differed from their predecessors on all these dimensions. Leshchinsky then compares urban and rural pogroms in Poland and provides detailed analyses of Polish mass pogroms in Grodno, Pshitik, Minsk-Mazovyetsk, and Adzhival. Finally, he argues that Poland is uniquely experiencing a “permanent pogrom,” a nearly three-year period of antisemitic violence during which assailants have killed hundreds of Jews and wounded about 10,000 in discrete acts of violence covering the entire country. Undated, 1937?
7. Ghetto benches
Authors: Leshchinsky Yankev
Published: September 2024

Widespread attacks on Warsaw’s Jews raged for two weeks in 1937. They were followed by a government commitment to institute ghetto benches throughout the Polish system of higher education. A numerus clausus on Jewish students had already sharply restricted Jewish admissions to institutions of higher education. In Warsaw, Jews constituted just 5 or 6% of admissions in the current academic year. At the Warsaw University of Technology’s faculty of engineering, Jewish admissions were less than 3% and Jewish admissions in the mechanics faculty were just over 1%. The situation was worse outside the capital. Separate benches for Jewish children are also being introduced in the public elementary schools. Many teachers were delighted when eight- or nine-year-old children assisted by dragging their Jewish classmates to separate seating. Meanwhile, the Jewish community has failed to form a united front of opposition to these developments. The leftist camp (Jewish and non-Jewish) is trying to form a united front of all opposition parties and groups, but nobody believes they will succeed in holding back the antisemitic tide. 26 October 1937.
9. Protests against pogroms
Authors: Leshchinsky Yankev
Published: September 2024

“The persecutions and pogroms are not causing Jews to despair, but rather cementing and uniting all classes and groups; they are not humiliating the Jews, but rather strengthening their courage and stoking their desire to fight.” Nearly all Polish Jews participated in the latest protest strike, proving that their spirit has not been broken. Poland’s Jews had just focused their attention for three weeks on the Pshitik pogrom trial, learning of the mass violence visited on that town’s Jewish population and the way in which organized armed Jews had for the first time attacked their assailants. They heard antisemitic lawyers call openly for pogroms and Jewish and Christian lawyers make “morally elevated and politically clever speeches” in defence of the Jews. They anticipated that justice would be served, but when they heard the outcome of the trial their despair swelled. They believed that the killing of Jews had now been endorsed by the courts. However, their despair was mixed with fury. On the initiative of the right wing of the Po’ale Tsiyon party, a general strike was called for 30 June 1936 between noon and 2 pm. “A quarter of a million shops and market stalls and 200,000 Jewish workshops closed in union across all Poland.” Jewish workers initiated, promoted, and led the strike but the Jewish bourgeoisie supported it. Only Agudes Yisroel urged Jews to fast rather than strike. In several locales, including Warsaw, Polish workers joined the strike, managing “to weave the struggle against antisemitism into the general struggle for freedom and a new order.” Jews were invigorated, as they had been by their earlier strike on 17 March. 22 July 1936 and 15 October 1937.
10. Old-fashioned methods in new times
Authors: Leshchinsky Yankev
Published: September 2024

In premodern times, Jews, when threatened, “would fast and pray to God to still the hand of the slaughterers, to turn the heart of the wicked lord or king toward goodness.” More recently, however, “a generation of Jewish revolutionaries…ridiculed and scoffed at the fasters, penitents, and self-flagellators” and fought against those who oppressed the Jews. Yet today, students have returned to fasting. Meanwhile, Jewish workers’ organization applaud them while, in Lodz, Jewish workers merely request that the authorities protect the Jewish population from attack rather than demanding action backed up by force. Undated, 1937?
Dark resonance: On the possibility of resonance with death
Authors: Ståhl Christian
Published: September 2024

The concept of resonance, introduced by Hartmut Rosa, denotes a vital relationship to the world and offers a starting point for discussing meaningfulness in peoples’ lives by serving as an antithesis to alienation. An unexplored aspect of the concept is the potential for resonance with death, which Rosa dismisses as an impossibility. This article challenges this view by introducing the term dark resonance, based on the ‘dark turn’ in the philosophy of nature. Dark resonance comes in (at least) two variants, both implying a transcendence of the self: (1) as reunion, an implosion of the self and an inwards movement, and (2) as release, an explosion of the self and an outwards movement. For both variants, the borders between self and environment and between life and death, becomes fuzzy, which also challenges the idea that resonance demands an experiencing subject. These variants are explored through examples from black metal, palliative care and near-death experiences. An implication is that we may need to broaden the scope of what can be seen as desirable ways of connecting to the world and acknowledge that there is potential for resonance also in dark thoughts, or, in some cases, even in death.
Living and Dying in Shadow Times
Authors: Ehlers Nadine , Broom Alex , Kenny Katherine
Published: September 2024

Normative time frameworks obscure the ontological ambiguities of lived time, particularly in relation to illness and death. These forms of ambiguous lived time constitute what we call ‘shadow time’ – the unnoticed and the unknowable in our dominant temporal order. We examine what we call ‘diagnostic time’, ‘prognostic time’, ‘terminal time’ and ‘mourning time’ as shades of shadow time that elude the ordering of time that orders life. A critical stance to temporality is necessary, we argue, in order to recognise the regulatory imperatives of normative time, to mark the slippages between the demands of normative time and how time is often lived (out) and, importantly, to do justice to those living in the complicated ontological ambiguities of lived shadow time – where we see the intricate folding of life and death
When Psalms Talk Back: How the Appropriation History of Psalms Challenges Contemporary Ritual-Musical Appropriations
Authors: Vogel Henk , Klomp Mirella , Barnard Marcel
Published: September 2024

This article discusses how, in contemporary Dutch and Flemish culture, the ritual-musical appropriations of Psalms in extra-ecclesial settings are challenged by the longer history of appropriating Psalms. Analyses of qualitative empirical research show that this history appears to challenge contemporary Psalm performances to address God, to perform Psalms collectively, and to contemplate life through these Psalms. Contemporary Psalm performances, thus, both continue the history of appropriating Psalms and are critiqued by this history. Evaluating the research results, we conclude that current appropriations tend to wipe away the Psalms’ ambiguity concerning images of God, the relationship between individual and community, and between hope and despair.
Public Health in a Transnational Context: Hong Kong and the Third Bubonic Plague Pandemic
Authors: Tang Y. H. Phoebe , Frost Lionel , Morgan Ruth , Gaynor Andrea
Published: September 2024

Originating in south-western China, the Third Plague Pandemic reached the Pearl River Delta in the early 1890s, whereupon steamships took the disease to port cities worldwide. We examine the impact of responses to plague on the built environment in Hong Kong, a British colony, as well as the comparable experiences of Honolulu and San Francisco. Bubonic plague is not the result of polluted water, but officials drawing on contemporary understandings of miasmic theory believed it to be so. Fearing the epidemic would spread beyond crowded Chinese districts, governments quarantined affected areas, carrying out house-to-house inspections and in America, controlled burnings of condemned buildings. To improve sanitation, the Hong Kong government commissioned reports that recommended a sewerage system, lower density housing, and rat control, but large-scale urban redevelopment was not undertaken due to high costs, and water infrastructure would prove to be ineffective in the face of twentieth-century population growth.
Lane-Change Decision of Automatic Driving Based on Reinforcement Learning Framework
Authors: Li Jiaxin , Liu Gang , Chen Zhiyu , Guo Jianwei
Published: September 2024

In highway traffic environment, vehicle lane-change decisions are a critical and difficult task for an agent. The traditional deep Q-network (DQN) has been the main architecture used for this task. However, DQN still faces two major challenges in solving the lane-changing decision-making problem for autonomous driving: 1) the instability in the training process leads to frequent collisions and 2) the single reward function limits the agent’s ability to learn representative domain knowledge about highways. To address these issues, this paper proposes a multi-reward DQN for highway driving decisions, with long short-term memory (LSTM) and self-attention. We call this model LAMRDQN. It incorporates LSTM and self-attention mechanism into Q-network to reduce frequent collisions. In addition, the unitary reward is changed into multiple reward functions—each reward emphasizing a specific factor, such as speed, obeying traffic rules, and lane changing. The use of multiple rewards enables the model to capture and optimize various aspects of autonomous driving on highway tasks, thereby obtaining more representative domain knowledge. The experiment results show that, in the highway environment, the method can effectively improve the problems of frequent collisions and poor learning performance when vehicles change lanes, and has better overtaking performance than related reinforcement learning algorithms.