bluuebunny/crossref_metadata_2025 huggingface dataset:
Figure S6 from The HSP90 Inhibitor Pimitespib Targets Regulatory T Cells in the Tumor Microenvironment
Authors: Tsuge Ayaka , Watanabe Sho , Kawazoe Akihito , Togashi Yosuke , Itahashi Kota , Masuda Mari , Sai Atsuo , Takei Shogo , Muraoka Hiromi , Ohkubo Shuichi , Sugiyama Daisuke , Yan Yue , Fukuoka Shota , Doi Toshihiko , Shitara Kohei , Koyama Shohei , Nishikawa Hiroyoshi
Published: February 2025

A schematic summary of the reduction in Treg cells by pimitespib. HSP90 inhibition by pimitespib impairs Treg cells via STAT5 degradation. The IL-2/STAT5 signaling pathway is essential for the development and maintenance of Treg cells (left). STAT5, a client protein of HSP90, is inhibited by pimitespib treatment, resulting in the inhibition of FOXP3 transcription. Decreased FOXP3 expression inhibits the development, maintenance, and immunosuppressive function of Treg cells (right). Treg cell impairment, therefore, is mainly caused by pimitespib–induced STAT5 degradation.
Figure S4 from The HSP90 Inhibitor Pimitespib Targets Regulatory T Cells in the Tumor Microenvironment
Authors: Tsuge Ayaka , Watanabe Sho , Kawazoe Akihito , Togashi Yosuke , Itahashi Kota , Masuda Mari , Sai Atsuo , Takei Shogo , Muraoka Hiromi , Ohkubo Shuichi , Sugiyama Daisuke , Yan Yue , Fukuoka Shota , Doi Toshihiko , Shitara Kohei , Koyama Shohei , Nishikawa Hiroyoshi
Published: February 2025

Pimitespib augments the antitumor efficacy of anti–PD-1 mAb. (A–C). Antitumor efficacy of combined treatment with anti–PD-1 mAb and pimitespib against CMT-93. A total of 2 × 106 CMT-93 cells were inoculated subcutaneously, and the cancer size was monitored twice weekly (n = 6). The mice were randomized, and some mice received intraperitoneal administration of anti–PD-1 mAb (0.5 mg/body) on that day (day 0) and/or oral administration of pimitespib (14 mg/kg/body) five times weekly from day 0. Cancer growth (A for summary and B for each mouse) and PFS (C) are shown. PFS was defined as the time from day 0 until the cancer was twice as large as when treatment was initiated. All in vivo experiments were performed at least twice. *, P < 0.05; **, P < 0.01.
Figure S3 from The HSP90 Inhibitor Pimitespib Targets Regulatory T Cells in the Tumor Microenvironment
Authors: Tsuge Ayaka , Watanabe Sho , Kawazoe Akihito , Togashi Yosuke , Itahashi Kota , Masuda Mari , Sai Atsuo , Takei Shogo , Muraoka Hiromi , Ohkubo Shuichi , Sugiyama Daisuke , Yan Yue , Fukuoka Shota , Doi Toshihiko , Shitara Kohei , Koyama Shohei , Nishikawa Hiroyoshi
Published: February 2025

Pimitespib–induced reduction in FOXP3 expression depends on STAT5 degradation in MJ cells. (A). Immunoprecipitation of HSP90 and STAT5. MJ cell lysates were incubated with normal rabbit IgG, anti-HSP90 mAb, or anti-STAT5 mAb, and immunocomplexes were purified, separated, and blotted. (B, C). The effect of STAT5B knockdown on FOXP3 expression. siRNA was used for knockdown of STAT5B (B). MJ cells after knockdown of STAT5B were cultured with the indicated concentrations of pimitespib for 48 hours. FOXP3 expression was examined in the MJ cells (C). (D). MJ cells were mock transduced or transduced with STAT5B to develop an MJ cells with STAT5b overexpression (OE). MJ cells with or without STAT5b overexpression were cultured in the presence or absence of pimitespib (1 μM) for 48 hours, and the mean fluorescence intensity (MFI) of FOXP3 was evaluated. (E). MJ cells were cultured with the indicated concentrations of pimitespib for 48 hours. Protein expression of the TCR-related signaling molecules LCK was examined. GAPDH was used as the internal control. All in vivo experiments were performed at least twice. **, P < 0.01; *, P < 0.05; **, P < 0.01; n.s., not significant.
Supplementary Table S6 from T Cells Instruct Immune Checkpoint Inhibitor Therapy Resistance in Tumors Responsive to IL1 and TNFα Inflammation
Authors: Cho Nam Woo , Guldberg Sophia M. , Nabet Barzin Y. , Yu Jie Zeng , Kim Eun Ji , Hiam-Galvez Kamir J. , Yee Jacqueline L. , DeBarge Rachel , Tenvooren Iliana , Ashitey Naa Asheley , Lynce Filipa , Dillon Deborah A. , Rosenbluth Jennifer M. , Spitzer Matthew H.
Published: February 2025

Supplementary Data Table S6
Supplementary Table S2 from T Cells Instruct Immune Checkpoint Inhibitor Therapy Resistance in Tumors Responsive to IL1 and TNFα Inflammation
Authors: Cho Nam Woo , Guldberg Sophia M. , Nabet Barzin Y. , Yu Jie Zeng , Kim Eun Ji , Hiam-Galvez Kamir J. , Yee Jacqueline L. , DeBarge Rachel , Tenvooren Iliana , Ashitey Naa Asheley , Lynce Filipa , Dillon Deborah A. , Rosenbluth Jennifer M. , Spitzer Matthew H.
Published: February 2025

Supplementary Data Table S2
Supplementary Figure S9 from T Cells Instruct Immune Checkpoint Inhibitor Therapy Resistance in Tumors Responsive to IL1 and TNFα Inflammation
Authors: Cho Nam Woo , Guldberg Sophia M. , Nabet Barzin Y. , Yu Jie Zeng , Kim Eun Ji , Hiam-Galvez Kamir J. , Yee Jacqueline L. , DeBarge Rachel , Tenvooren Iliana , Ashitey Naa Asheley , Lynce Filipa , Dillon Deborah A. , Rosenbluth Jennifer M. , Spitzer Matthew H.
Published: February 2025

Supplementary Data Figure S9
Supplementary Figure S6 from T Cells Instruct Immune Checkpoint Inhibitor Therapy Resistance in Tumors Responsive to IL1 and TNFα Inflammation
Authors: Cho Nam Woo , Guldberg Sophia M. , Nabet Barzin Y. , Yu Jie Zeng , Kim Eun Ji , Hiam-Galvez Kamir J. , Yee Jacqueline L. , DeBarge Rachel , Tenvooren Iliana , Ashitey Naa Asheley , Lynce Filipa , Dillon Deborah A. , Rosenbluth Jennifer M. , Spitzer Matthew H.
Published: February 2025

Supplementary Data Figure S6
Supplementary Figure S4 from T Cells Instruct Immune Checkpoint Inhibitor Therapy Resistance in Tumors Responsive to IL1 and TNFα Inflammation
Authors: Cho Nam Woo , Guldberg Sophia M. , Nabet Barzin Y. , Yu Jie Zeng , Kim Eun Ji , Hiam-Galvez Kamir J. , Yee Jacqueline L. , DeBarge Rachel , Tenvooren Iliana , Ashitey Naa Asheley , Lynce Filipa , Dillon Deborah A. , Rosenbluth Jennifer M. , Spitzer Matthew H.
Published: February 2025

Supplementary Data Figure S4
Table S6 from Targeting of Tumoral NAC1 Mitigates Myeloid-Derived Suppressor Cell–Mediated Immunosuppression and Potentiates Anti–PD-1 Therapy in Ovarian Cancer
Authors: Dong Shunli , Ye Cong , Li Bin , Lv Fanglin , Zhang Lu , Yang Shumin , Wang Fang , Zhu Mingxian , Zhou Mingxuan , Guo Fanfan , Li Zhenyun , Peng Lei , Ji Cheng , Lu Xialiang , Cheng Yan , Ren Xingcong , Chen Youguo , Zhou Jinhua , Yang Jinming , Zhang Yi
Published: February 2025

Table S6. Statistical data on CXCL16 expression in relation to clinic-histopathologic features for surgical ovarian tumor specimens.
Table S5 from Targeting of Tumoral NAC1 Mitigates Myeloid-Derived Suppressor Cell–Mediated Immunosuppression and Potentiates Anti–PD-1 Therapy in Ovarian Cancer
Authors: Dong Shunli , Ye Cong , Li Bin , Lv Fanglin , Zhang Lu , Yang Shumin , Wang Fang , Zhu Mingxian , Zhou Mingxuan , Guo Fanfan , Li Zhenyun , Peng Lei , Ji Cheng , Lu Xialiang , Cheng Yan , Ren Xingcong , Chen Youguo , Zhou Jinhua , Yang Jinming , Zhang Yi
Published: February 2025

Table S5. Statistical data on NAC1 expression in relation to clinic-histopathologic features for surgical ovarian tumor specimens.
Supplementary Figure S13 from T Cells Instruct Immune Checkpoint Inhibitor Therapy Resistance in Tumors Responsive to IL1 and TNFα Inflammation
Authors: Cho Nam Woo , Guldberg Sophia M. , Nabet Barzin Y. , Yu Jie Zeng , Kim Eun Ji , Hiam-Galvez Kamir J. , Yee Jacqueline L. , DeBarge Rachel , Tenvooren Iliana , Ashitey Naa Asheley , Lynce Filipa , Dillon Deborah A. , Rosenbluth Jennifer M. , Spitzer Matthew H.
Published: February 2025

Supplementary Data Figure S13
Table S4 from Targeting of Tumoral NAC1 Mitigates Myeloid-Derived Suppressor Cell–Mediated Immunosuppression and Potentiates Anti–PD-1 Therapy in Ovarian Cancer
Authors: Dong Shunli , Ye Cong , Li Bin , Lv Fanglin , Zhang Lu , Yang Shumin , Wang Fang , Zhu Mingxian , Zhou Mingxuan , Guo Fanfan , Li Zhenyun , Peng Lei , Ji Cheng , Lu Xialiang , Cheng Yan , Ren Xingcong , Chen Youguo , Zhou Jinhua , Yang Jinming , Zhang Yi
Published: February 2025

Table S4. Clinical information of TCGA-OV cohort.
Supplementary Figure S12 from T Cells Instruct Immune Checkpoint Inhibitor Therapy Resistance in Tumors Responsive to IL1 and TNFα Inflammation
Authors: Cho Nam Woo , Guldberg Sophia M. , Nabet Barzin Y. , Yu Jie Zeng , Kim Eun Ji , Hiam-Galvez Kamir J. , Yee Jacqueline L. , DeBarge Rachel , Tenvooren Iliana , Ashitey Naa Asheley , Lynce Filipa , Dillon Deborah A. , Rosenbluth Jennifer M. , Spitzer Matthew H.
Published: February 2025

Supplementary Data Figure S12
Supplementary Figure S11 from T Cells Instruct Immune Checkpoint Inhibitor Therapy Resistance in Tumors Responsive to IL1 and TNFα Inflammation
Authors: Cho Nam Woo , Guldberg Sophia M. , Nabet Barzin Y. , Yu Jie Zeng , Kim Eun Ji , Hiam-Galvez Kamir J. , Yee Jacqueline L. , DeBarge Rachel , Tenvooren Iliana , Ashitey Naa Asheley , Lynce Filipa , Dillon Deborah A. , Rosenbluth Jennifer M. , Spitzer Matthew H.
Published: February 2025

Supplementary Data Figure S11
Supplementary Figure S10 from T Cells Instruct Immune Checkpoint Inhibitor Therapy Resistance in Tumors Responsive to IL1 and TNFα Inflammation
Authors: Cho Nam Woo , Guldberg Sophia M. , Nabet Barzin Y. , Yu Jie Zeng , Kim Eun Ji , Hiam-Galvez Kamir J. , Yee Jacqueline L. , DeBarge Rachel , Tenvooren Iliana , Ashitey Naa Asheley , Lynce Filipa , Dillon Deborah A. , Rosenbluth Jennifer M. , Spitzer Matthew H.
Published: February 2025

Supplementary Data Figure S10
Table S2 from Targeting of Tumoral NAC1 Mitigates Myeloid-Derived Suppressor Cell–Mediated Immunosuppression and Potentiates Anti–PD-1 Therapy in Ovarian Cancer
Authors: Dong Shunli , Ye Cong , Li Bin , Lv Fanglin , Zhang Lu , Yang Shumin , Wang Fang , Zhu Mingxian , Zhou Mingxuan , Guo Fanfan , Li Zhenyun , Peng Lei , Ji Cheng , Lu Xialiang , Cheng Yan , Ren Xingcong , Chen Youguo , Zhou Jinhua , Yang Jinming , Zhang Yi
Published: February 2025

Table S2. Primers used for CRISPR/Cas9 gene editing system, qRT-PCR and ChIP in this study
Supplementary Figure 4 from Inflammatory Stress Determines the Need for Chemotherapy in Patients with HER2-Positive Esophagogastric Adenocarcinoma Receiving Targeted Therapy and Immunotherapy
Authors: Tintelnot Joseph , Paschold Lisa , Goekkurt Eray , Schultheiss Christoph , Matschl Urte , Santos Cruz Mariana , Bauer Marcus , Wickenhauser Claudia , Thuss-Patience Peter , Lorenzen Sylvie , Ettrich Thomas J. , Riera-Knorrenschild Jorge , Jacobasch Lutz , Kretzschmar Albrecht , Kubicka Stefan , Al-Batran Salah-Eddin , Reinacher-Schick Anke , Pink Daniel , Bokemeyer Carsten , Sinn Marianne , Lindig Udo , Hinke Axel , Hegewisch-Becker Susanna , Stein Alexander , Binder Mascha
Published: February 2025

Supplementary Figure 4: PFS in selected patients and overall survival of NLR > 5 patients. (A) PFS in months is shown for patients selected by CPS ≥ 1, HER2-3+, and NLR < 5 within the Ipi arm (n=12). Median PFS was 20.9 months. (B) Final overall survival is shown for the Ipi vs FOLFOX arm of NLR >5 preselected patients. Number of patients at risk are indicated. Log-rank test was performed (B).
Supplementary Figure S9 from Targeting of Tumoral NAC1 Mitigates Myeloid-Derived Suppressor Cell–Mediated Immunosuppression and Potentiates Anti–PD-1 Therapy in Ovarian Cancer
Authors: Dong Shunli , Ye Cong , Li Bin , Lv Fanglin , Zhang Lu , Yang Shumin , Wang Fang , Zhu Mingxian , Zhou Mingxuan , Guo Fanfan , Li Zhenyun , Peng Lei , Ji Cheng , Lu Xialiang , Cheng Yan , Ren Xingcong , Chen Youguo , Zhou Jinhua , Yang Jinming , Zhang Yi
Published: February 2025

Figure S9. Pharmacologic inhibition NAC1 by NIC3 potentiates anti–PD-1 therapy.
Supplementary Figure 3 from Inflammatory Stress Determines the Need for Chemotherapy in Patients with HER2-Positive Esophagogastric Adenocarcinoma Receiving Targeted Therapy and Immunotherapy
Authors: Tintelnot Joseph , Paschold Lisa , Goekkurt Eray , Schultheiss Christoph , Matschl Urte , Santos Cruz Mariana , Bauer Marcus , Wickenhauser Claudia , Thuss-Patience Peter , Lorenzen Sylvie , Ettrich Thomas J. , Riera-Knorrenschild Jorge , Jacobasch Lutz , Kretzschmar Albrecht , Kubicka Stefan , Al-Batran Salah-Eddin , Reinacher-Schick Anke , Pink Daniel , Bokemeyer Carsten , Sinn Marianne , Lindig Udo , Hinke Axel , Hegewisch-Becker Susanna , Stein Alexander , Binder Mascha
Published: February 2025

Supplementary Figure 3: Low NLR defines patients with superior survival in the Ipi arm.
Supplementary Figure S4 from Targeting of Tumoral NAC1 Mitigates Myeloid-Derived Suppressor Cell–Mediated Immunosuppression and Potentiates Anti–PD-1 Therapy in Ovarian Cancer
Authors: Dong Shunli , Ye Cong , Li Bin , Lv Fanglin , Zhang Lu , Yang Shumin , Wang Fang , Zhu Mingxian , Zhou Mingxuan , Guo Fanfan , Li Zhenyun , Peng Lei , Ji Cheng , Lu Xialiang , Cheng Yan , Ren Xingcong , Chen Youguo , Zhou Jinhua , Yang Jinming , Zhang Yi
Published: February 2025

Figure S4. NAC1 increases MDSCs infiltration and suppresses anti-tumor immunity.
Supplementary Figure S1 from Targeting of Tumoral NAC1 Mitigates Myeloid-Derived Suppressor Cell–Mediated Immunosuppression and Potentiates Anti–PD-1 Therapy in Ovarian Cancer
Authors: Dong Shunli , Ye Cong , Li Bin , Lv Fanglin , Zhang Lu , Yang Shumin , Wang Fang , Zhu Mingxian , Zhou Mingxuan , Guo Fanfan , Li Zhenyun , Peng Lei , Ji Cheng , Lu Xialiang , Cheng Yan , Ren Xingcong , Chen Youguo , Zhou Jinhua , Yang Jinming , Zhang Yi
Published: February 2025

Figure S1. The gating strategy utilized in flow cytometric analysis of immune cells.
Supplementary Figure S1 from Hyperthermic Intrathoracic Chemotherapy Modulates the Immune Microenvironment of Pleural Mesothelioma and Improves the Impact of Dual Immune Checkpoint Inhibition
Authors: Hao Yameng , Gkasti Aspasia , Managh Amy J. , Dagher Julien , Sifis Alexandros , Tiron Luca , Chriqui Louis-Emmanuel , Marie Damien N. , De Souza Silva Olga , Christodoulou Michel , Peters Solange , Joyce Johanna A. , Krueger Thorsten , Gonzalez Michel , Abdelnour-Berchtold Etienne , Sempoux Christine , Clerc Daniel , Teixeira-Farinha Hugo , Hübner Martin , Meylan Etienne , Dyson Paul J. , Cavin Sabrina , Perentes Jean Y.
Published: February 2025

Supplementary Figure S1: Evaluation of the impact of heat adjunct on cisplatin cytotoxicity.
Data from Setdb1 Loss Induces Type I Interferons and Immune Clearance of Melanoma
Authors: McGeary Meaghan K. , Damsky William , Daniels Andrew J. , Lang Sabine M. , Xu Qingji , Song Eric , Huet-Calderwood Clotilde , Lou Hua Jane , Paradkar Sateja , Micevic Goran , Kaech Susan M. , Calderwood David A. , Turk Benjamin E. , Yan Qin , Iwasaki Akiko , Bosenberg Marcus W.
Published: February 2025

Abstract
Despite recent advances in the treatment of melanoma, many patients with metastatic disease still succumb to their disease. To identify tumor-intrinsic modulators of immunity to melanoma, we performed a whole-genome CRISPR screen in melanoma and identified Setdb1 as well as all components of the human silencing hub complex. We found that loss of Setdb1 leads to increased immunogenicity and complete tumor clearance in a CD8+ T cell–dependent manner. Mechanistically, loss of Setdb1 causes de-repression of endogenous retroviruses (ERV) in melanoma cells and triggers tumor cell–intrinsic type I IFN signaling, upregulation of MHC-I expression, and increased CD8+ T-cell infiltration. Importantly, spontaneous immune clearance observed in Setdb1−/− tumors results in subsequent protection from other ERV-expressing tumor lines, supporting the functional antitumor role of ERV-specific CD8+ T cells found in the Setdb1−/− microenvironment. Blocking the type I IFN receptor in mice grafted with Setdb1−/− tumors decreases immunogenicity by decreasing MHC-I expression, leading to decreased T-cell infiltration and increased melanoma growth, comparable with Setdb1wt tumors. Together, these results provide key in vivo evidence of a critical role for Setdb1 and type I IFNs in generating an inflamed tumor microenvironment and potentiating tumor cell–intrinsic immunogenicity in melanoma. This study further emphasizes regulators of ERV expression and type I IFN expression as potential therapeutic targets for augmenting anticancer immune responses.
Data from Hyperthermic Intrathoracic Chemotherapy Modulates the Immune Microenvironment of Pleural Mesothelioma and Improves the Impact of Dual Immune Checkpoint Inhibition
Authors: Hao Yameng , Gkasti Aspasia , Managh Amy J. , Dagher Julien , Sifis Alexandros , Tiron Luca , Chriqui Louis-Emmanuel , Marie Damien N. , De Souza Silva Olga , Christodoulou Michel , Peters Solange , Joyce Johanna A. , Krueger Thorsten , Gonzalez Michel , Abdelnour-Berchtold Etienne , Sempoux Christine , Clerc Daniel , Teixeira-Farinha Hugo , Hübner Martin , Meylan Etienne , Dyson Paul J. , Cavin Sabrina , Perentes Jean Y.
Published: February 2025

Abstract
Pleural mesothelioma is a fatal disease with limited treatment options. Recently, pleural mesothelioma management has improved with the development of immune checkpoint inhibitors (ICI). In first-line therapy, dual PD-1 and CTLA-4 blockade enhances tumor control and patient survival compared with chemotherapy. Unfortunately, only a fraction of patients is responsive to immunotherapy, and approaches to reshape the tumor immune microenvironment and make ICIs more effective are urgently required. In this study, we evaluated the effect of hyperthermic intrathoracic chemotherapy (HITOC), a treatment that combines fever-range hyperthermia with local intrapleural cisplatin chemotherapy, on the tumor immune microenvironment and response to ICIs. To do this, we developed a murine pleural mesothelioma model of HITOC. We found that HITOC significantly improved tumor control and animal survival through a mechanism involving the development of a cytotoxic immune response. Additionally, HITOC enhanced immune checkpoint expression by T lymphocytes and synergized with dual PD-1 and CTLA-4 inhibition, leading to further improvement in animal survival. Finally, the analysis of peritoneal mesothelioma patient samples treated by pressurized intraperitoneal aerosol chemotherapy revealed a similar immunomodulation. In conclusion, HITOC remodels the tumor immune microenvironment of pleural mesothelioma by promoting T-cell infiltration into the tumor and could be considered in combination with ICIs in the context of a clinical trial.
Supplementary Figure 4 from Loss of NF1 Accelerates Uveal and Intradermal Melanoma Tumorigenesis, and Oncogenic GNAQ Transforms Schwann Cells
Authors: Longakit Anne Nathalie , Urtatiz Oscar , Luty Amy , Zhang Christina , Hess Chloe , Yoo Alyssa , Bourget Hannah , Van Raamsdonk Catherine D.
Published: February 2025

Supplementary Figure 4
Supplementary Figure 3 from Loss of NF1 Accelerates Uveal and Intradermal Melanoma Tumorigenesis, and Oncogenic GNAQ Transforms Schwann Cells
Authors: Longakit Anne Nathalie , Urtatiz Oscar , Luty Amy , Zhang Christina , Hess Chloe , Yoo Alyssa , Bourget Hannah , Van Raamsdonk Catherine D.
Published: February 2025

Supplementary Figure 3
Supplementary Figure 2 from Loss of NF1 Accelerates Uveal and Intradermal Melanoma Tumorigenesis, and Oncogenic GNAQ Transforms Schwann Cells
Authors: Longakit Anne Nathalie , Urtatiz Oscar , Luty Amy , Zhang Christina , Hess Chloe , Yoo Alyssa , Bourget Hannah , Van Raamsdonk Catherine D.
Published: February 2025

Supplementary Figure 2
Figure 1 from Loss of NF1 Accelerates Uveal and Intradermal Melanoma Tumorigenesis, and Oncogenic GNAQ Transforms Schwann Cells
Authors: Longakit Anne Nathalie , Urtatiz Oscar , Luty Amy , Zhang Christina , Hess Chloe , Yoo Alyssa , Bourget Hannah , Van Raamsdonk Catherine D.
Published: February 2025

Effects of heterozygous Nf1 loss on skin pigmentation in mice expressing oncogenic GNAQ. A, Tails of mice injected with tamoxifen at 5 weeks of age at various indicated time points after injection. The Plp1-creERT/+; R26-fs-GNAQQ209L/+; Nf1flox/+ mice developed skin hyperpigmentation 8 weeks after injection when the Plp1-creERT/+; R26-fs-GNAQQ209L/+; +/+ mice still looked normal. B, Hyperpigmented tail skin in both Plp1-creERT/+; R26-fs-GNAQQ209L/+; Nf1flox/+ and Plp1-creERT/+; R26-fs-GNAQQ209L/+; +/+ mouse tails at 35 weeks after injection, compared with that in their uninjected littermates. C and D, H&E analysis of tail skin from Plp1-creERT/+; R26-fs-GNAQQ209L/+; Nf1flox/+ and Plp1-creERT/+; R26-fs-GNAQQ209L/+; +/+ mice at 35 weeks after injection, with an uninjected control mouse tail skin section. Yellow boxes in C are enlarged in D. E, Hyperpigmented and thickened ear skin with small pigmented lesions in mice of the indicated genotypes.
Research Trends of Traditional Chinese Medicine Therapies on Chronic Obstructive Pulmonary Disease: A Bibliometric Analysis
Authors: Yang Chunyan , He Qiying , Huang Liuyang , Tian Hao , Luo Qin , Xu Guixing , Sun Mingsheng , Yang Sha , Liang Fanrong , Litao Pan
Published: February 2025

Background: Traditional Chinese Medicine (TCM) therapies have shown great improvement in chronic obstructive pulmonary disease (COPD) patients, yet no bibliometric analysis on TCM therapies for COPD exists. Summary: A comprehensive literature search was conducted on TCM therapies for COPD within the past decade, utilizing the Web of Science (WOS) Core Collection and China National Knowledge Infrastructure (CNKI) databases. To analyze collaborative patterns among countries/regions, institutions, and authors, as well as identify influential references and emerging research trends, CiteSpace and VOSviewer software were employed. The dataset comprised 625 articles from WOS and 5,641 from CNKI, revealing a consistent growth in COPD-related TCM research over the past 10 years. China emerged as the leading contributor, with a predominant focus on TCM Universities. The American Journal of Respiratory and Critical Care Medicine was the most cited journal, while Medicine published the highest number of articles. Li JS was the most prolific author, and Barnes PJ was the most frequently cited researcher. Key studies by Leung RWM [Eur Respir J. 2013;41(5):1051–7], Li SY [BMC Complement Altern Med. 2012;12:197], and Polkey MI [Chest. 2018;153(5):1116–24] garnered significant attention. Keyword analysis highlighted the prominence of Tai Chi, Chinese herbal medicine, acupoint sticking, acupuncture, lung function, quality of life, and inflammation as core research themes. Key Messages: Research on TCM therapies for COPD has gained growing attention over the past decade. Among the most commonly studied TCM interventions are Tai Chi, Chinese herbal medicine, acupoint sticking, and acupuncture. Lung function, quality of life, and inflammation have emerged as key areas of investigation and are likely to remain focal points for future research endeavors.
Use of Macrogol to accelerate feeding advancement in extremely preterm infants
Authors: Faust Kirstin Barbara , Lupatsii Mariia , Römer Frederike , Graspeuntner Simon , Waschina Silvio , Zimmermann Sina , Humberg Alexander , Fortmann Mats Ingmar , Hanke Kathrin , Böckenholt Kai , Dirks Johannes , Silwedel Christine , Rupp Jan , Herting Egbert , Göpel Wolfgang , Härtel Christoph
Published: February 2025

Introduction
Delayed enteral nutrition is associated with a higher risk for adverse outcomes in extremely preterm infants. Limited evidence exists on therapeutic options to support meconium evacuation and increase gastrointestinal motility. The aim of this study was to determine the effect of macrogol on feeding tolerance and microbiome establishment in preterm infants < 27 weeks of gestation.
Methods
We investigated the impact of early macrogol administration in two observational cohort studies: the multi-center German-Neonatal-Network (GNN) study comparing extremely preterm infants born in Neonatal intensive care units (NICUs) using macrogol in the first week of life in >30% of their infants as compared to the remaining units, and the single center Immunoregulation-of-the-Newborn (IRoN) study including gut microbiome assessment of infants born before and after implementation of macrogol use in this NICU.
Results
In the GNN study cohort including 4290 infants, advancement to full enteral feedings was significantly faster in macrogol-using NICUs compared to the remaining NICUs (median/SD: 14/16.5 vs. 16/16.7days, p=0.001). Risk for short-term outcomes such as sepsis or abdominal complications was not elevated in units with regular use of macrogol. In the IRoN cohort (n=68), macrogol treated infants had a shorter time to reach full enteral feeding (median/SD: Macrogol 12/4.8, Control 16/6.6days, p=0.004). Higher Bifidobacterium longum abundance in the gut microbiome correlated with acceleration to full enteral nutrition.
Conclusion
Our observational data suggests that early off-label use of macrogol may support feeding advancement in highly vulnerable babies. These data provide a basis for a randomized controlled trial.
Belzutifan bei retinalen Hämangiomen im Rahmen eines Von-Hippel-Lindau-Syndroms
Authors: Seibel Ira
Published: February 2025

Introduction: The systemic HIF-2 alpha inhibitor, belzutifan, has been approved for use in patients with von Hippel-Lindau disease (VHL)-associated renal cell carcinoma, central nervous system (CNS) hemangioblastomas, and pancreatic neuroendocrine tumors. This drug has also shown promise in controlling VHL retinal hemangioblastomas (RHs), but little work has been published on the use of the drug in this setting. Methods: We conducted a retrospective review of patients with VHL-associated RHs followed by the retina service at our institution who were treated with systemic belzutifan. Patient age, gender, genotype, presence of systemic tumors, indication for the drug, initial dose, adjusted dose, side effects, and tumor response were recorded. We also conducted a literature search for all manuscripts describing the effect of belzutifan on VHL-associated ocular tumors. Results: We identified 12 eyes of 7 patients with VHL-associated ocular tumors who were treated with belzutifan at our institution. Of these, 5 eyes of 3 patients had progressing ocular tumors when belzutifan was started. Of the 7 total patients, 2 were treated for renal cell carcinoma, 2 for CNS hemangioblastomas, 2 for RHs, and one for pancreatic neuroendocrine tumors. Initial dose was 120 mg PO daily in 6 patients and 80 mg PO daily in 1 patient. The dose was reduced in all but 1 patient due to side effects. The ocular tumors were controlled in all patients with an average follow-up of 13 months (range 4–24 months). Literature review identified 7 manuscripts that described belzutifan-mediated control of ocular tumors in patients with VHL-associated RHs in 21 patients. Conclusion: The drug belzutifan shows great promise for controlling RHs and preventing vision loss in patients with VHL. Further work needs to address the optimal dose, role of the drug as a neoadjuvant therapy, and long-term efficacy and tolerability of the drug in a larger cohort of patients with ocular tumors.
Hidden Resources for Cancer Patients – Interactions between spirituality, religiosity and selected factors influencing patient’s self-care
Authors: Ruhe Sebastian , Orawa Helmut , Huebner Jutta , Büntzel Jens
Published: February 2025

Introduction. Religiosity and spirituality (SpR) can be vital in helping people face life's challenges. While Spiritual Care (SpC) is used in palliative care, this study explores effects for cancer patient’s self-care (SC) in earlier stages .
Methods. Using validated instruments we surveyed patients about SpR (SpNQ-20, GrAw-7, SpREUK), and factors of SC: well-being (WHO-5, L-1), self-efficacy (ASKU), ability to change (PIAC), as well as lay etiology and the use of Complementary and alternative Medicine (CAM). Data were analyzed using SPSS according a three-step plan with descriptive methods, Spearman correlations and mediation analysis.
Results. We included 108 patients (41 female, 63 males, four no data) with a median age of 66 years (range 30-89). Welch tests show a less well-being, self-efficacy and ability to change in our study population (p < 0.05) compared to non-cancer controls. Whitney-U-test has documented increased well-being, CAM use if the patients were S/R+ (p < 0.05). S/R self-categorization had no impact on PIAC and ASKU. Perceptual spirituality (GrAw-7) correlates with all factors of SC (p < 0.05): WHO-5 (rs = 0.25), PIAC (rs = 0.25), ASKU (rs = 0.296), L-1 (rs = 0.35) and CAM use (rs = 0.39, p < 0.001). Mediation analysis demonstrates that the impact of Spirituality on self-care (CAM use) is mediated by religiosity, GrAw-7 and spiritual needs.
Conclusion. Spirituality and hidden spiritual needs are a valuable resource. By integrating SpC early in the treatment, we can create support ways and improve SC, well-being and coping.
Research Article
Useful bowel preparation with ultralow-volume (500 ml) polyethylene glycol for colonoscopy: a retrospective study
Authors: Mizuno Yusuke , Shimura Takaya , Nukui Takayuki , Uno Konomu , Nishigaki Ruriko , Kojima Yuki , Kannno Takuya , Sasaki Makiko , Fukusada Shigeki , Sugimura Naomi , Tanaka Mamoru , Ozeki Keiji , Kubota Eiji , Kataoka Hiromi
Published: February 2025

Introduction: Adequate bowel preparation is indispensable for high-quality colonoscopy. We have developed an ultralow-volume (500 ml) polyethylene glycol (PEG) combined with other laxatives (sennoside, sodium picosulfate, and lactulose) and applied this regimen clinically to all patients with colonoscopy for three decades. This study aimed to assess the effectiveness of this ultralow-volume bowel preparation regimen.
Methods: This single-center, retrospective study analyzed data from consecutive outpatients who underwent colonoscopy between January 2022 and December 2022. All the patients took sennoside (24 mg) two nights before, sodium picosulfate (75 mg) one night before, and 500 ml of PEG with lactulose (58.5 g) on the day of examination. Cleaning efficacy was evaluated using the Boston Bowel Preparation Scale (BBPS). Adequate bowel preparation was defined as a total BBPS score ≥ 6, with all colon segments scoring ≥ 2.
Results: Out of 862 patients with colonoscopy, 773 were eligible for this study, and the median age was 66 years. The adequate bowel preparation rate was 91.8% (710/773). Notably, the BBPS full score “9” was observed in 50.5% (390/773). The median cecal intubation time and examination time were 8 and 20 min, respectively. Only three patients vomited as a side effect. In the multivariate analysis, age ≥ 70 years, diabetes mellitus, and diverticula were significantly independent risk factors for inadequate bowel preparation.
Conclusions: Our established ultralow-volume (500 ml) PEG is safe and useful as a bowel preparation method.
Predictors of mortality in a large cohort of elders with essential tremor
Authors: Carter Ericka D. , Berry Diane S. , Cosentino Stephanie , Louis Elan D.
Published: February 2025

Background: Prospective data show an increased risk of mortality in essential tremor (ET). Understanding the contributors to this increased mortality is of value.
Methods: 347 cases enrolled in a prospective study of cognition in elders with ET (M baseline age = 79.6 years, M follow-up length = 2.7 years). At each visit, cases completed clinical assessments, a cognitive test battery and were assigned a Clinical Dementia Rating (CDR). Cox proportional hazards regression equations identified predictors of cases’ relative risk of mortality.
Results: 41 (11.8%) of 347 cases died during follow-up. Deceased cases were older at baseline, had fewer years of education, used more medication, had more severe tremor, had more gait impairment, and reported more falls, less physical activity, and more depressive symptoms than did living cases. In univariate analyses, a CDR score of 1 or 2 (dementia) was associated with a six-fold increased the risk of mortality (Hazards ratio, HR = 6.33). Moderate rather than milder levels of dementia (CDR 2 rather than 1) were driving this effect, with multivariate models demonstrating HRs in excess of 7.5 (p <0.001). Gait impairment and falls were also associated with significant increased risk of mortality in multivariate models.
Conclusion: We identified several factors that may be used to risk-stratify ET patients with respect to mortality. The information from these analyses can be of value in identifying subgroups of ET patients who demonstrate risk for early death; such subgroups can then be targeted for interventions as well as preventive measures.
A challenging case of recurrent cholangitis caused by isolated bile duct metastasis of colorectal adenocarcinoma – rescue therapy through EUS-guided hepaticoesophagostomy.
Authors: Vara-Luiz Francisco , Mendes Ivo , Nunes Gonçalo , Palma Carolina , Patita Marta , Pinto-Marques Pedro
Published: February 2025

A 64-year-old male was admitted with fever, abdominal pain and jaundice. Medical history was relevant for colorectal adenocarcinoma eleven years before and right hepatectomy due to liver metastasis. MRCP revealed left hepatic duct stenosis without liver nodules. ERCP was performed for biliary drainage with plastic stents. After inconclusive brush cytology, cholangioscopy (Spyglass™DS2) was performed showing villous mucosa surrounded by irregular vessels suggestive of tumor neovascularization. Spybite™ biopsies confirmed biliary metastasis of colorectal origin.
The patient started palliative chemotherapy being readmitted six months later with acute cholangitis. Diffuse infiltrating intrabiliary lesion with 120mm was detected in control MRCP. Given its intraductal extension and gastric compression by the hypertrophied liver leading to duodenoscope mispositioning, transpapilar stents could not be deployed. Multiorgan dysfunction developed despite broad-spectrum antibiotics and EUS-guided biliary drainage was proposed. Although EUS access was limited by gastric bulging, puncture of a dilated intrahepatic duct was accomplished with a 19G needle. PCSEMS (GIOBOR™8x100mm) placement was only possible above the gastroesophageal junction with the proximal flare being incidentally deployed in a 3cm intraparietal esophageal tract. The misplaced stent was immediately recanalized and a stent-in-stent FCSEMS (Wallflex™80x10mm) allowed the hepaticoesophagostomy creation. Since the stent opening was orally oriented in esophageal lumen, parenteral nutrition was started to avoid contamination. Sepsis recovering and liver tests normalization were observed.
Before hospital discharge stent reposition was planned to resume oral feeding. After placement of a third stent-in-stent NCSEMS (Wallflex™120x10mm) in the hepaticoesophagostomy to prevent migration, the proximal flare was oriented to the stomach gently pushing with the endoscope aiding by an inflated biliary balloon. The patient resumed chemotherapy but died 8 months after due to disease progression.
Isolated bile duct metastasis is an uncommon complication of colorectal cancer. EUS-guided hepaticoesophagostomy is feasible when puncture through the esophagus was inevitable, especially in patients with liver hypertrophy.
Implementing the Nurse-led Optimization of Volume and blood pressure – Enabling at multi-Levels using TechnologY (NOVELTY) program for Chronic Kidney Disease: a prospective cohort study
Authors: Huang Zhihua , Ng Li Choo , Mok Irene , Tan Chieh Suai , Lim Cynthia Ciwei
Published: February 2025

Background: Fluid overload is a common manifestation of chronic kidney disease (CKD) and is associated with increased hospitalizations and death. However, severe symptomatic fluid overload is potentially preventable with early recognition of mild fluid overload and timely institution of appropriate pharmacotherapy and fluid restriction. We implemented and evaluated the outcomes of a nurse-led clinic that incorporated objective fluid volume assessment using body impedance analysis (BIA) into structured patient education and action plan coaching to patients with CKD and fluid overload.
Methods: Single-center prospective pre- post implementation study of adults who participated in the program (Table 1) between August 2022 and April 2024. Patients were eligible if they had CKD not requiring dialysis and had fluid overload and/or systolic blood pressure (BP) >160 mmHg or diastolic BP >100 mmHg. The clinical effectiveness outcomes were symptoms and signs of fluid overload and improvement in blood pressure. The patient-reported effectiveness outcomes were chronic disease self-management assessed using the Partner in Health (PIH) questionnaire and health-related quality of life (HrQOL) assessed by the EuroQOL-5 Dimension (EQ5D5L) survey. The clinical safety outcomes were hypotension and worsening kidney function.
Results: Among 107 patients referred to the nurse-led program, 96 attended the first visit. median age was 68.5 (IQR 60.2, 77.3) years and eGFR was 21.6 (14.0, 39.7) ml/min/1.73 m2. Almost all participants (93.8%) had symptoms of fluid overload within the past 1 month before the first review. BIA was performed for 52 (54.2%) patients and the median overhydration was 2.4 (1.3, 3.6) liters. The second and third visits were attended by 38 (39.6%) and 28 (29.2%) patients, respectively. At program completion, patients had reduced symptoms and signs of fluid overload and had improved systolic BP [137 (121, 143) versus 151 (132, 166) mmHg, p=0.03] and self-management [PIH score 96 (89, 104) versus 72 (57, 88), p=0.001] compared to their baseline visit. EQ5D5L scores were significantly different. None experienced hypotension (systolic BP <90 mmHg) and kidney function did not change significantly during follow-up.

Conclusions: A nurse-led program that incorporated objective fluid volume assessment, structured patient education and action plan coaching for patients with CKD and fluid overload improved BP and self-management.
Economic structural change over time: Brazil and the United States compared
Authors: Guilhoto Joaquim J. M. , Hewings Geoffrey J. D. , Sonis Michael , Guo Jiemin
Published: February 2025

Usando as matrizes de insumo-produto para as economias do Brasil e dos Estados Unidos, este estudo comparativo tem como objetivo analisar como a estrutura produtiva de dois grandes países, com níveis diferentes de desenvolvimento, mudou através do tempo (1958-77 para os Estados Unidos e 1959-80 para o Brasil). A mudança na estrutura produtiva e decomposta em três componentes iniciais (demanda final, tecnologia, e sua interação sinergética), após o que estes componentes são divididos em mudanças que são iniciadas dentro e fora do setor. A partir destas analises e possível identificar os padrões de mudanças estruturais nas duas economias. Os resultados indicam um grande grau de semelhança nos padrões do processo de crescimento de ambos os países, com diferenças mais significantes entre setores do que entre países. A análise capaz de capturar diferenças importantes na origem das mudanças da demanda, isto e mudanças internas versus mudanças externas ao setor.
Custo ambiental: impactos econômicos dos sedimentos na geração de energia elétrica
Authors: Marques João Fernando , Comune Antônio Evaldo
Published: February 2025

O artigo estima o valor econômico dos danos ambientais causados pelo processo erosão-sedimentação do solo, com base nos efeitos no sistema de geração de energia elétrica. Os impactos nesse sistema vão desde a redução na capacidade de armazenamento de água dos reservatórios, o aumento nas atividades de manutenção das usinas hidrelétricas, ate a redução do número de dias de operação da usina. Utilizou-se o metodo do custo de reposição e da produção sacrificada para calcular o valor monetário do dano ambiental causado pelo assoreamento do rio Sapucai. O valor econômico do dano ambiental mostrou ser de expressiva grandeza na hipótese de assoreamento severo. Este valor e maior que o investimento necessário para a aquisição de um conjunto de geração de energia da mesma capacidade geradora que aquele danificado pelos sedimentos.
Determinants of the evolution of the unemployment structure in Brazil; 1986-1995
Authors: Corseuil Carlos Henrique , Reis Carla , Urani André
Published: February 2025

Este trabalho descreve a evolução da estrutura do desemprego no Brasil, entre os anos de 1986 e 1995, e analisa os determinantes das mudanças ocorridas, à luz de decomposições logarítmicas. As conclusões mais importantes são as seguintes: a) a principal contrapartida da redução do emprego formal não foi o desemprego, mas o emprego sem carteira assinada e as ocupações por conta própria; b) o principal fator explicativo do aumento do peso de homens, chefes de família e indivíduos entre 30 e 60 anos no desemprego foi o fato do aumento das taxas de desemprego destes grupos ter superado o geral; c) o aumento da importância relativa dos cônjuges no desemprego esteve associado à elevação de sua taxa de participação na PEA; d) foi o fator demográfico (composição da PIA) o principal responsável pelas alterações de composição do desemprego entre faixas de escolaridade.
Estatísticas oficiais: credibilidade, reputação e coordenação
Authors: Feijo Carmem Aparecida
Published: February 2025

This paper calls attention to the role of the official statistics in the decision process of modern economies. Official statistics, to become well accepted, should be credible and the official producer should have a good reputation. In this sense, we identify that the discussion about quality in the production of official statistics should stress the distinction between credibility of the statistics and the reputation of the official producer. Also we add thatthe new System of National Accounts plays an important role as an instrument ofcoordenation in the decentralized production of official statistics.
Arborização pública na zona de amortecimento do Parque Estadual da Serra da Tiririca - Niterói/Maricá - Rio de Janeiro – Brasil
Authors: Barros Ana Angélica Monteiro de , Machado Davi Nepomuceno da Silva , Siqueira André Costa , Rocha Nathalia Otaviano da
Published: February 2025

Urban afforestation includes both natural and cultivated tree vegetation from city, with its implementation being carried out through afforestation plans. This document designates suitable species for the urban environment, emphasizing the importance of scientific basis to prioritize native flora. This study evaluated the urban afforestation plans of the municipalities of Niterói and Maricá, Rio de Janeiro, categorizing species as recommended/suitable or unsuitable for urban afforestation. Additionally, a case study was conducted to understand which species compose the Buffer Zone of the Serra da Tiririca State Park (PESET), and to address the issue of using exotic species in the vicinity of this Conservation Unit (UC). The afforestation plans were analyzed for species richness, origin, and dispersal method of recommended species. Unsuitable species were identified along with the reasons for their non-use. The study focused on the Buffer Zone of PESET, up to 700 meters from the UC boundary, covering 65 kilometers and selecting 14 areas to assess the presence of exotic plants in urban afforestation. Species were recorded and photographed, encompassing not only trees but also other forms of life.
Imagens da devastação - registros do desmatamento da floresta brasileira ao longo do século XIX e em princípios do século XX
Authors: Aragão Solange de , Sandeville Júnior Euler
Published: February 2025

Este artigo revela imagens da devastação da floresta brasileira produzidas ao longo do século XIX e em princípios do século XX. Essas imagens compreendem gravuras, fotografias, relatos de viagem e textos produzidos por estudiosos, além de trechos de obras literárias, que apresentam ou representam os processos de queimada de áreas florestadas ou a derrubada de árvores nessas áreas. Demonstram também que a destruição das florestas, reconhecidas pelos estrangeiros como a maior riqueza do Brasil, atraiu o olhar de artistas, fotógrafos, escritores e poetas que admiravam a natureza brasileira, em especial a vegetação da Mata Atlântica e da Floresta Amazônica. O objetivo deste trabalho é apresentar essas imagens e convidar o leitor a refletir sobre esse processo de devastação das áreas florestadas em território nacional.
Assessing the Relevance of the Kansas City Cardiomyopathy Questionnaire in Patients With Tricuspid Regurgitation: The Tri-QOL Qualitative Study
Authors: Olds Danielle M. , Smith Jamie L. , Spertus John A. , Dunlay Shannon M. , Bocell Fraser D. , Wu Changfu , Cohen David J. , Arnold Suzanne V.
Published: February 2025

BACKGROUND:

Validly measuring disease-specific health status is critical in patients with severe tricuspid regurgitation (TR) to quantify the benefit of different interventions. The Kansas City Cardiomyopathy Questionnaire (KCCQ) has been used to assess health status in patients with severe TR, but its content validity in this patient population is unknown, including whether additional questions are needed to supplement the KCCQ.

METHODS:

Twenty participants with symptomatic severe TR from 2 midwestern clinical sites were interviewed in 2023 using a semistructured guide. The interview guide addressed symptoms, physical and social functioning, and quality of life concepts of the KCCQ, as well as other potential TR symptoms not represented in the KCCQ. Interview transcripts were analyzed using inductive and deductive coding and content analysis, with additional participants recruited until thematic saturation occurred.

RESULTS:

Mean age of the participants was 80 (41–89), and 75% were female. Shortness of breath and fatigue were reported by virtually all participants (n=20 and n=19, respectively) and had a marked negative impact on their physical and social functioning and quality of life. Lower limb edema was also reported by 10 participants. Although these concepts are captured by the KCCQ, other symptoms were also reported, including appetite loss (n=8) and upper body edema (n=4), but did not seem to markedly affect participants’ function or quality of life. In addition, all participants who experienced these other symptoms reported symptoms that were already captured by the KCCQ.

CONCLUSIONS:

All participants experienced symptoms captured by the KCCQ, and these symptoms had a substantial impact on their physical and social functioning and quality of life. Although some participants reported additional symptoms not assessed by the KCCQ, their incorporation would only marginally improve content validity. Thus, the current KCCQ appears to be appropriate for capturing the disease-specific health status of patients with severe TR.
Obtusitermes monomorphus, a new termite species (Isoptera: Termitidae: Nasutitermitinae) from Panama
Authors: SCHEFFRAHN RUDOLF H. , ROISIN YVES , WANG MENGLIN , BOURGUIGNON THOMAS , HELLEMANS SIMON
Published: February 2025

Obtusitermes monomorphus sp. nov. is described from the monomorphic soldier and worker castes. The two described congeners, O. panamae (Snyder, 1924) and O. formosulus Cuezzo and Cancello, 2009 both have dimorphic soldiers and workers. It is now demonstrated that the major worker hindgut of all three Obtusitermes species are unique among other termite taxa in due to the first proctodeal segment connected to the third proctodeal segment by a very long and tubular enteric valve (second proctodeal segment) with weak armature at both ends and a curvature of 180°. Additionally, Obtusitermes monomorphus is compared with other small monomorphic nasutitermitines of Panama.