bluuebunny/crossref_metadata_2025 huggingface dataset:
Figure S6 from Immunoproteasome Activation Expands the MHC Class I Immunopeptidome, Unmasks Neoantigens, and Enhances T-cell Anti-Myeloma Activity
Authors: Rana Priyanka S. , Ignatz-Hoover James J. , Guo Chunna , Mosley Amber L. , Malek Ehsan , Federov Yuriy , Adams Drew J. , Driscoll James J.
Published: December 2024

Figure S6. Effect of Compound A on the viability of ARH77 and U266 cells alone or combined with ICIs and CD8+ T-cells. Similar to as shown in Fig. 7f, MM and CD8+ T-cells were separately treated with or without Compound A and the indicated agents (BTZ, TGFβ, ICIs). Following co-culture, the relative percent of viable MM cells was quantitated by annexin-V and propidium iodide staining and flow cytometry. Assays were performed in triplicate.
Figure S4 from Immunoproteasome Activation Expands the MHC Class I Immunopeptidome, Unmasks Neoantigens, and Enhances T-cell Anti-Myeloma Activity
Authors: Rana Priyanka S. , Ignatz-Hoover James J. , Guo Chunna , Mosley Amber L. , Malek Ehsan , Federov Yuriy , Adams Drew J. , Driscoll James J.
Published: December 2024

Figure S4. Effect of Compound A on murine H2Kb MHC-I-SIINFEKL presentation and B3Z tumor lysis. a. Effect of the eight hits on proteasomal ChT-like activity at increasing concentrations in E.G7-ova cells. Compounds that increased proteasome ChT-like activity >1.5-fold and maintained cell viability >50% are represented by red boxes. b. Effect of the eight hits on proteasomal ChT-like activity and SIINFEKL-MHC-I complex presentation in E.G7-ova cells. E.G7-Ova cells were pre-treated with the indicated compounds for 72 h after which they were stained with a monoclonal antibody to SIINFEKL-bound to H2Kb. Fluorescence was quantitated by flow cytometry. Red boxes indicate compounds that increased proteasomal activity >1.5-fold, and increased SIINFEKL-H2Kb presentation >2-fold. c. Effect of the eight hits that increased proteasomal ChT-like activity with SIINFEKL-MHC-I complex presentation on lysis of E.G7-Ova cells by the B3Z T-cells. E.G7-Ova cells were pretreated with compounds (1 uM) after which cells were washed and co-cultured with the H-2Kb-restricted B3Z T-cells genetically engineered to express a TCR that specifically recognizes the SIINFEKL-H2Kb complex. E.G7-Ova cells were co-cultured with B3Z cells at E:T ratios of 1:1, 2:1, and 3:1.
Supplementary Table S3 from Separable Cell Cycle Arrest and Immune Response Elicited through Pharmacological CDK4/6 and MEK Inhibition in RASmut Disease Models
Authors: Wu Jin , Wang Jianxin , O’Connor Thomas N. , Tzetzo Stephanie L. , Gurova Katerina V. , Knudsen Erik S. , Witkiewicz Agnieszka K.
Published: December 2024

Supplementary Table S3. RAS mutation status in target cell models.
Supplementary Data File 1 from Targeting the Synthetic Lethal Relationship between FOCAD and TUT7 Represents a Potential Therapeutic Opportunity for TUT4/7 Small-Molecule Inhibitors in Cancer
Authors: Triboulet Robinson , Sadykov Khikmet , Harvey Darren M. , Wilson David M. , Steinbaugh Michael J. , Mayo Christopher B. , Hawley Dillon , Madanjian Andrew , Fyfe Corey , Bracken Christina , Rivera-Rivera Izarys , Ericsson Anna , Snyder Andrew R. , Knutson Sarah K. , Stein Ross L. , Gibaja Veronica , Ghosh Shomir , Campbell Robert M.
Published: December 2024

Supplementary Data File 1
Supplemental Fig. S4 from Trametinib Potentiates Anti-PD-1 Efficacy in Tumors Established from Chemotherapy-Primed Pancreatic Cancer Cells
Authors: Pham Thao D. , Metropulos Anastasia E. , Mubin Nida , Becker Jeffrey H. , Shah Dhavan , Spaulding Christina , Shields Mario A. , Bentrem David J. , Munshi Hidayatullah G.
Published: December 2024

Supplemental Fig. S4. SN38 does not have single-agent antiproliferative activity against KPC and KPC-FIO cells. A-D. The parental KPC and KPC-FIO cells were treated with increasing doses of SN38 (12.5, 25, 50, 100 nM). After 72 hours, the effects of drug treatments on cell proliferation were evaluated by WST1 assay and analyzed by GraphPad. Error bars ± SEM from 3 biological replicates. One-way ANOVA, followed by Dunnett multiple comparison test. ns, non-significant.
Supplemental Fig. S2 from Trametinib Potentiates Anti-PD-1 Efficacy in Tumors Established from Chemotherapy-Primed Pancreatic Cancer Cells
Authors: Pham Thao D. , Metropulos Anastasia E. , Mubin Nida , Becker Jeffrey H. , Shah Dhavan , Spaulding Christina , Shields Mario A. , Bentrem David J. , Munshi Hidayatullah G.
Published: December 2024

Supplemental Fig. S2. KPC-FIO cells display reduced sensitivity to 5FU (F), irinotecan (I), oxaliplatin (O), and the FIO combination. A-H. The parental KPC (2138, 3886, 3213, and 1245) and KPC-FIO (2138-FIO, 3886-FIO, 3213-FIO, and 1245-FIO) cells were treated with vehicle control, 4 µM 5FU (F), 12.5 nM SN38 (I), 0.5 µM oxaliplatin (O), or a combination of the three drugs (FIO). The effects of drug treatments on cell proliferation after 72 hours were evaluated by WST1 assay and cell death after 48 hours by annexin V/PI staining. Error bars ± SEM. One-way ANOVA, followed by Dunnett multiple comparison test. **, p<0.05 ***, p<0.001 ****, p<0.0001 ns, non-significant.
Supplemental Fig. S1 from Trametinib Potentiates Anti-PD-1 Efficacy in Tumors Established from Chemotherapy-Primed Pancreatic Cancer Cells
Authors: Pham Thao D. , Metropulos Anastasia E. , Mubin Nida , Becker Jeffrey H. , Shah Dhavan , Spaulding Christina , Shields Mario A. , Bentrem David J. , Munshi Hidayatullah G.
Published: December 2024

Supplemental Fig. S1. Gating strategy to determine the frequency of T cells (CD45+CD4+ or CD45+CD8+), T cell functions (TNFα, Perforin1 (Prf1), IFNγ, Granzyme B (GzmB)), the frequency of tumor-associated macrophages (TAMs; CD45+CD11b+F4/80+), granulocytic myeloid derived suppressor cells (G-MDSCs; CD45+CD11b+Ly6G + Ly6C-), monocytic myeloid derived suppressor cells (M-MDSCs; CD45+CD11b+Ly6G-Ly6G+) and their functions (CD206, PD-L1, Arginase1 (Arg1)). All cells are gated from live single cells.
Supplementary Figure S1 from Integrated Imaging Probe and Bispecific Antibody Development Enables In Vivo Targeting of Glypican-3–Expressing Hepatocellular Carcinoma
Authors: Habibollahi Peiman , Gurevich Alexey , Hui James Z. , Weinfurtner Kelly , McClung George , Adler Justin , Soulen Michael C. , Kaplan David E. , Nadolski Gregory J. , Hunt Stephen J. , Tsourkas Andrew , Gade Terence P.
Published: December 2024

Supplementary Figure S1: Expression and Purification of TRAB Recombinant Protein. Synthesized TRAB gene fragments (IDT DNA, Coralville, IA), as specified in figure above (A), were inserted into a pTXB1 (New England Biolabs) vector using standard restriction enzyme based cloning techniques. Insertion of the TRAB sequence was verified by DNA sequencing using the T7 promoter as the sequencing primer. The TRAB-pTXB1 plasmids were then transformed into a competent E coli expression cell line (Origami 2 Cells, Novagen). Bacterial cell cultures were initially grown overnight in an air shaker (225 rpm) at 37°C in 3 mL of lysogeny broth (LB) media, eventually inoculated into scaled up 1 L LB media containing 50 mg/L of ampicillin. At optical density (OD) 600 nm = 0.6, Isopropyl β-D-1-thiogalactopyranoside (IPTG) was added to a final concentration of 0.5 mM to induce T7 RNA polymerase-based expression. Cultures were allowed to express for 2 h at 37°C. Bacterial cultures were centrifugally pelleted at 10,000 g for 30 min, resuspended in 5 mL of column buffer (20 mM Na-HEPES, 0.5 M NaCl, 1 mM EDTA, pH 8.5) containing 0.75 g/L lysozyme and 50 mM phenylmethylsulfonyl fluoride. Cells were lysed by pulse sonication on ice. Cell lysate was centrifuged at 15,000 g for 30 min at 4°C. Supernatant was then loaded and incubated in Poly-Prep chromatography column (Bio-Rad, Hercules, CA) packed with Talon metal affinity resin (Clontech, Mountain View, CA). Supernatant was then allowed to pass through the column and resin beads were washed with multiple rounds of column buffer (0.1 M Tris-HCl, pH 8.5). Bound and washed TRAB protein (sequence shown in panel B) was then released from metal resin via the addition of 200 mM imidazole-containing elution buffer. Purification and concentration of the final product was performed using a 3 kDa molecular weight cutoff (MWCO) filter (Amicon Ultra, Milipore, Temecula, CA). The final product was analyzed on SDS-PAGE protein gel (Figure 2), with confirmation of the protein band at the expected molecular weight.
Data from Discovery of RGT-018: A Potent, Selective, and Orally Bioavailable SOS1 Inhibitor for KRAS-Driven Cancers
Authors: Xiao Fei , Wang Kailiang , Wang Xinjuan , Li Huijuan , Hu Zhilong , Ren Xiaoming , Huang Wei , Feng Teng , Yao Lili , Lin Jing , Li Chunlai , Zhang Zhuanzhuan , Mei Liufeng , Zhu Xiaotian , Zhong Wenge , Xie Zhi
Published: December 2024

Abstract
KRAS is the most frequently dysregulated oncogene with a high prevalence in non–small cell lung cancer, colorectal cancer, and pancreatic cancer. FDA-approved sotorasib and adagrasib provide breakthrough therapies for patients with cancer with KRASG12C mutation. However, there is still high unmet medical need for new agents targeting broader KRAS-driven tumors. An emerging and promising opportunity is to develop a pan KRAS inhibitor by suppressing the upstream protein of Son of Sevenless 1 (SOS1). SOS1 is a key activator of KRAS and facilitates the conversion of GDP-bound KRAS state to GTP-bound KRAS state. Binding to its catalytic domain, small-molecule SOS1 inhibitor has demonstrated the ability to suppress KRAS activation and cancer cell proliferation. RGT-018, a potent and selective SOS1 inhibitor, was identified with optimal drug-like properties. In vitro, RGT-018 blocked the interaction of KRAS:SOS1 with single-digit nanomoles per liter potency and was highly selective against SOS2. RGT-018 inhibited KRAS signaling and the proliferation of a broad spectrum of KRAS-driven cancer cells as a single agent in vitro. Further enhanced antiproliferation activity was observed when RGT-018 was combined with MEK, KRASG12C, EGFR, or CDK4/6 inhibitors. Oral administration of RGT-018 inhibited tumor growth and suppressed KRAS signaling in tumor xenografts in vivo. Combinations with MEK or KRASG12C inhibitors led to significant tumor regression. Furthermore, RGT-018 overcame the resistance to the approved KRASG12C inhibitors caused by clinically acquired KRAS mutations either as a single agent or in combination. RGT-018 displayed promising pharmacological properties for combination with targeted agents to treat a broader KRAS-driven patient population.
Data from Trametinib Potentiates Anti-PD-1 Efficacy in Tumors Established from Chemotherapy-Primed Pancreatic Cancer Cells
Authors: Pham Thao D. , Metropulos Anastasia E. , Mubin Nida , Becker Jeffrey H. , Shah Dhavan , Spaulding Christina , Shields Mario A. , Bentrem David J. , Munshi Hidayatullah G.
Published: December 2024

Abstract
Despite advances in immune checkpoint inhibitors, chemotherapy remains the standard therapy for patients with pancreatic ductal adenocarcinoma (PDAC). As the combinations of chemotherapy, including the FOLFIRINOX [5-fluorouracil, F; irinotecan, I; and oxaliplatin, O (FIO)] regimen, and immune checkpoint inhibitors have failed to demonstrate clinical benefit in patients with metastatic PDAC tumors, there is increasing interest in identifying therapeutic approaches to potentiate ICI efficacy in patients with PDAC. In this study, we report that neoadjuvant FOLFIRINOX-treated human PDAC tumors exhibit increased MEK/ERK activation. We also show elevated MEK/ERK signaling in ex vivo PDAC slice cultures and cell lines treated with a combination of FIO. In addition, we find that the KPC-FIO cells, established from repeated treatment of mouse PDAC cell lines with six to eight cycles of FIO, display enhanced ERK phosphorylation and demonstrate increased sensitivity to MEK inhibition in vitro and in vivo. Significantly, the KPC-FIO cells develop tumors with a proinflammatory immune profile similar to human PDAC tumors after neoadjuvant FOLFIRINOX treatment. Furthermore, we found that the MEK inhibitor trametinib enables additional infiltration of highly functional CD8+ T cells into the KPC-FIO tumors and potentiates the efficacy of anti-PD-1 antibody in syngeneic mouse models. Our findings provide a rationale for combining trametinib and anti-PD-1 antibodies in patients with PDAC after neoadjuvant or short-term FOLFIRINOX treatment to achieve effective antitumor responses.
Supplementary Figure-5 from TEAD2 Promotes Hepatocellular Carcinoma Development and Sorafenib Resistance via TAK1 Transcriptional Activation
Authors: Zhang Yahui , Ren Yidan , Dong Guoying , Jiao Qinlian , Guo Nan , Gao Ping , Li Ya , Wang Yunshan , Zhao Wei
Published: December 2024

Supplementary Figure-5
Supplementary Figure 3 from Ruthenium Drug BOLD-100 Regulates BRAFMT Colorectal Cancer Cell Apoptosis through AhR/ROS/ATR Signaling Axis Modulation
Authors: Griffin Daryl , Carson Robbie , Moss Debbie , Sessler Tamas , Lavin Deborah , Tiwari Vijay K. , Karelia Shivaali , Kennedy Richard , Savage Kienan I. , McDade Simon , Carie Adam , Pankovich Jim , Bazett Mark , Van Schaeybroeck Sandra
Published: December 2024

Treatment with BOLD-100 rewires the signalling network of BRAFMT CRC cells.
Figure 5 from Ruthenium Drug BOLD-100 Regulates BRAFMT Colorectal Cancer Cell Apoptosis through AhR/ROS/ATR Signaling Axis Modulation
Authors: Griffin Daryl , Carson Robbie , Moss Debbie , Sessler Tamas , Lavin Deborah , Tiwari Vijay K. , Karelia Shivaali , Kennedy Richard , Savage Kienan I. , McDade Simon , Carie Adam , Pankovich Jim , Bazett Mark , Van Schaeybroeck Sandra
Published: December 2024

Oncogenic BRAF regulates BOLD-100 induced ROS, ATR/CHK1 activation and cell death. A, HT-29 and VACO432 cells were treated with BOLD-100 for the indicated times and pATRT1989, ATR, pKAP1S824, KAP1, pCKH1S345, CHK1, and γH2AX levels determined by WB. B, HT-29 cells were preincubated with 1umol/l vemurafenib for 3 hours and thereafter treated with 50 μmol/L BOLD-100 for 48 hours and pATRT1989, ATR, pKAP1S824, KAP1, pCKH1S345, CHK1, γH2AX, pMEK1/2S217/221, MEK, PARP, and cleaved caspase-3 expression determined by WB. C, WB analyzes for pATRT1989, ATR, pCKH1S345, CHK1, γH2AX, PARP, and BRAF in VT1 cells transiently transfected with 1 µg of BRAFV600E expression construct for 12 hours followed by treatment with BOLD-100 for the indicated times. D, VACO432 and HT-29 cells (top) were treated with BOLD-100 for indicated times and ROS levels assessed using the ROS-Glo H2O2 Assay Kit. ROS detection (bottom left) by flow cytometry in VACO432 and VT1 cells following treatment with 50 μmol/L BOLD-100 for 48 hours. ROS detection  (bottom middle/right) by flow cytometry in VACO432 and HT-29 cells, preincubated with vemurafenib for 3 hours, followed by 48 hours treatment with 50 μmol/L BOLD-100. MFI, mean fluorescence intensity. E, Cells were preincubated with NAC for 6 hours and thereafter treated with BOLD-100 for 48 hours and ROS levels assessed using the ROS-Glo H2O2 Assay Kit. F, Cells were preincubated with 5 mmol/L NAC for 6 hours and thereafter treated with BOLD-100 for the indicated times and γH2AX, pATRT1989, ATR, pKAP1S824, KAP1, pCKH1S345, and CHK1 levels determined by WB. G, Colorectal cancer cells were preincubated with 5 mmol/L NAC for 6 hours and thereafter treated with BOLD-100 for 48 hours and apoptosis was assessed by WB analysis for PARP (left) and caspase-3/7 activity assays (right). CONT, control; VEM, vemurafenib; B-100, BOLD-100.
Supplementary Table 10 from EHMT1/2 Inhibition Promotes Regression of Therapy-Resistant Ovarian Cancer Tumors in a CD8 T-cell–Dependent Manner
Authors: Nguyen Lily L. , Watson Zachary L. , Ortega Raquel , Woodruff Elizabeth R. , Jordan Kimberly R. , Iwanaga Ritsuko , Yamamoto Tomomi M. , Bailey Courtney A. , To Francis , Lin Shujian , Villagomez Fabian R. , Jeong Abigail D. , Guntupalli Saketh R. , Behbakht Kian , Gibaja Veronica , Arnoult Nausica , Chuong Edward B. , Bitler Benjamin G.
Published: December 2024

Hallmark pathways negatively enriched in ID8-R cells treated with combinatory UNC0642/Olaparib compared to Olaparib alone.
Supplementary Figure 4 from Oncogenic HRAS Induces Metformin Resistance in Head and Neck Cancer by Promoting Glycolytic Metabolism
Authors: Wu Xingyu , Adame-Garcia Sendi Rafael , Koshizuka Keiichi , Vo Pham Thuy Tien , Hoang Thomas S. , Sato Kuniaki , Izumi Hiroki , Goto Yusuke , Allevato Michael M. , Wood Kris C. , Lippman Scott M. , Gutkind Jorge Silvio
Published: December 2024

Supplementary Figure 4: Synergistic effects of Metformin and Dichloroacetate (DCA) in HNSCC cell lines
Supplementary Figure 3 from Oncogenic HRAS Induces Metformin Resistance in Head and Neck Cancer by Promoting Glycolytic Metabolism
Authors: Wu Xingyu , Adame-Garcia Sendi Rafael , Koshizuka Keiichi , Vo Pham Thuy Tien , Hoang Thomas S. , Sato Kuniaki , Izumi Hiroki , Goto Yusuke , Allevato Michael M. , Wood Kris C. , Lippman Scott M. , Gutkind Jorge Silvio
Published: December 2024

Supplementary Figure 3: Metabolic profiling of CAL27 Control and HRAS mutant cells reveals changes in ATP production and oxygen consumption rates.
Supplementary Figure 2 from Oncogenic HRAS Induces Metformin Resistance in Head and Neck Cancer by Promoting Glycolytic Metabolism
Authors: Wu Xingyu , Adame-Garcia Sendi Rafael , Koshizuka Keiichi , Vo Pham Thuy Tien , Hoang Thomas S. , Sato Kuniaki , Izumi Hiroki , Goto Yusuke , Allevato Michael M. , Wood Kris C. , Lippman Scott M. , Gutkind Jorge Silvio
Published: December 2024

Supplementary Figure 2: metformin sensitivity in HRAS-mutant HNSCC cells
Supplementary Movie 4 from Targeting BTN2A1 Enhances Vγ9Vδ2 T-Cell Effector Functions and Triggers Tumor Cell Pyroptosis
Authors: Le Floch Anne-Charlotte , Imbert Caroline , Boucherit Nicolas , Gorvel Laurent , Fattori Stéphane , Orlanducci Florence , Le Roy Aude , Archetti Lorenzo , Crescence Lydie , Panicot-Dubois Laurence , Dubois Christophe , Vey Norbert , Briantais Antoine , Anastasio Amandine , Cano Carla , Guittard Geoffrey , Frechin Mathieu , Olive Daniel
Published: December 2024

Visualization of Vγ9Vδ2 T cells (E) and Ishikawa (T) coculture using a label-free method within 20 hours. Ratio T/E = 1/2. Cells treated with 107G3B5 antibody (10ug/ml).
Figure S7 from Targeting BTN2A1 Enhances Vγ9Vδ2 T-Cell Effector Functions and Triggers Tumor Cell Pyroptosis
Authors: Le Floch Anne-Charlotte , Imbert Caroline , Boucherit Nicolas , Gorvel Laurent , Fattori Stéphane , Orlanducci Florence , Le Roy Aude , Archetti Lorenzo , Crescence Lydie , Panicot-Dubois Laurence , Dubois Christophe , Vey Norbert , Briantais Antoine , Anastasio Amandine , Cano Carla , Guittard Geoffrey , Frechin Mathieu , Olive Daniel
Published: December 2024

Supplementary Figure S7. 107G3B5 primes Vγ9Vδ2T cells by mechanisms that are dependent on BTN3A and BTN2Abut independent of the pAg-binding B30.2 intracellular domain.
Figure S10 from CAR T Cells Engineered to Secrete IFNκ Induce Tumor Ferroptosis via an IFNAR/STAT1/ACSL4 Axis
Authors: Gao Yaoxin , Liu Shasha , Huang Yifan , Wang Hui , Zhao Yuyu , Cui Xuyang , Peng Yajing , Li Feng , Zhang Yi
Published: December 2024

IFN-κ improved tumor repression via enhancing CAR-T cells function and ferroptosis in vivo.
Figure S3 from Targeting BTN2A1 Enhances Vγ9Vδ2 T-Cell Effector Functions and Triggers Tumor Cell Pyroptosis
Authors: Le Floch Anne-Charlotte , Imbert Caroline , Boucherit Nicolas , Gorvel Laurent , Fattori Stéphane , Orlanducci Florence , Le Roy Aude , Archetti Lorenzo , Crescence Lydie , Panicot-Dubois Laurence , Dubois Christophe , Vey Norbert , Briantais Antoine , Anastasio Amandine , Cano Carla , Guittard Geoffrey , Frechin Mathieu , Olive Daniel
Published: December 2024

Supplementary Figure S3. BTN2A1 is broadly expressed at the tumor cells surface.
Supplementary Table 3 from Cannabidiol Enhances Atezolizumab Efficacy by Upregulating PD-L1 Expression via the cGAS–STING Pathway in Triple-Negative Breast Cancer Cells
Authors: Kim Bu Gyeom , Kim Bo Ram , Kim Dae Yeong , Kim Woo Young , Kang Sanghee , Lee Sun Il , Oh Sang Cheul
Published: December 2024

Primer sequence for ChIP-PCR assay
Supplementary Figure 4 from Cannabidiol Enhances Atezolizumab Efficacy by Upregulating PD-L1 Expression via the cGAS–STING Pathway in Triple-Negative Breast Cancer Cells
Authors: Kim Bu Gyeom , Kim Bo Ram , Kim Dae Yeong , Kim Woo Young , Kang Sanghee , Lee Sun Il , Oh Sang Cheul
Published: December 2024

The combination of CBD and atezolizumab stimulated an anti-cancer immune response in a co-culture system
Figure S5 from Inflammation Mediated by Gut Microbiome Alterations Promotes Lung Cancer Development and an Immunosuppressed Tumor Microenvironment
Authors: Rahal Zahraa , Liu Yuejiang , Peng Fuduan , Yang Sujuan , Jamal Mohamed A. , Sharma Manvi , Moreno Hannah , Damania Ashish V. , Wong Matthew C. , Ross Matthew C. , Sinjab Ansam , Zhou Tieling , Chen Minyue , Tarifa Reischle Inti , Feng Jiping , Chukwuocha Chidera , Tang Elizabeth , Abaya Camille , Lim Jamie K. , Leung Cheuk Hong , Lin Heather Y. , Deboever Nathaniel , Lee Jack J. , Sepesi Boris , Gibbons Don L. , Wargo Jennifer A. , Fujimoto Junya , Wang Linghua , Petrosino Joseph F. , Ajami Nadim J. , Jenq Robert R. , Moghaddam Seyed Javad , Cascone Tina , Hoffman Kristi , Kadara Humam
Published: December 2024

Supplementary figure S5. Different species belonging to the genus Alistipes promote the development of LUAD.
Table S3 from CD91 and Its Ligand gp96 Confer Cross-Priming Capabilities to Multiple APCs during Immune Responses to Nascent, Emerging Tumors
Authors: Nayak Devanshi A. , Sedlacek Abigail L. , Cillo Anthony R. , Watkins Simon C. , Binder Robert J.
Published: December 2024

DEGs- DP versus SP APCs
Table S4 from Peripheral Blood–Derived PD-1/CD28–CD19 CAR–Modified PD-1+ T-Cell Therapy in Patients with Solid Tumors
Authors: Zhang Zhen , Zhao Xuan , Zhao Qitai , Chen Xinfeng , Li Congcong , Liu Yaqing , Shen Chunyi , Song Lijie , Miao Lijun , Guo Fuyou , Mou Xiaoning , Zhao Jie , Gu Weiyue , Zhang Yi
Published: December 2024

Characteristics of data for scRNA-seq.
Figure S3 from CD91 and Its Ligand gp96 Confer Cross-Priming Capabilities to Multiple APCs during Immune Responses to Nascent, Emerging Tumors
Authors: Nayak Devanshi A. , Sedlacek Abigail L. , Cillo Anthony R. , Watkins Simon C. , Binder Robert J.
Published: December 2024

Supplementary Figure 3. Single-cell sequencing of CD11c+ APCs in the tumor-draining lymph nodes.
Figure S16 from CD91 and Its Ligand gp96 Confer Cross-Priming Capabilities to Multiple APCs during Immune Responses to Nascent, Emerging Tumors
Authors: Nayak Devanshi A. , Sedlacek Abigail L. , Cillo Anthony R. , Watkins Simon C. , Binder Robert J.
Published: December 2024

Supplementary figure 16. Single-cell analysis to compare APC subsets.
Figure S15 from CD91 and Its Ligand gp96 Confer Cross-Priming Capabilities to Multiple APCs during Immune Responses to Nascent, Emerging Tumors
Authors: Nayak Devanshi A. , Sedlacek Abigail L. , Cillo Anthony R. , Watkins Simon C. , Binder Robert J.
Published: December 2024

Supplementary figure 15. Separation of gp96-mediated anti-tumor immune function within APC subsets.
Figure S1 from CD91 and Its Ligand gp96 Confer Cross-Priming Capabilities to Multiple APCs during Immune Responses to Nascent, Emerging Tumors
Authors: Nayak Devanshi A. , Sedlacek Abigail L. , Cillo Anthony R. , Watkins Simon C. , Binder Robert J.
Published: December 2024

Supplementary Figure 1. Dendritic cells in CD91 conditional knockouts under normal physiological conditions.
Figure S1 from Peripheral Blood–Derived PD-1/CD28–CD19 CAR–Modified PD-1+ T-Cell Therapy in Patients with Solid Tumors
Authors: Zhang Zhen , Zhao Xuan , Zhao Qitai , Chen Xinfeng , Li Congcong , Liu Yaqing , Shen Chunyi , Song Lijie , Miao Lijun , Guo Fuyou , Mou Xiaoning , Zhao Jie , Gu Weiyue , Zhang Yi
Published: December 2024

Supplementary Figure S1. Construction of PD-1/CD28 receptor, CD19 CAR and PD-1/CD28-T2A-CD19 CAR.
Supplementary Tables S4 from Spatially Resolved Whole-Transcriptomic and Proteomic Profiling of Lung Cancer and Its Immune Microenvironment According to PD-L1 Expression
Authors: Koh Jaemoon , Lee Dongjoo , Kim Sehui , Song Seung Geun , Han Bogyeong , Jeong Hyein , Kim Young A , Keam Bhumsuk , Lee Se-Hoon , Kim Kwangsoo , Jeon Yoon Kyung , Chung Doo Hyun
Published: December 2024

List of protein molecules identified using nCounter analysis
Supplementary Tables S3 from Spatially Resolved Whole-Transcriptomic and Proteomic Profiling of Lung Cancer and Its Immune Microenvironment According to PD-L1 Expression
Authors: Koh Jaemoon , Lee Dongjoo , Kim Sehui , Song Seung Geun , Han Bogyeong , Jeong Hyein , Kim Young A , Keam Bhumsuk , Lee Se-Hoon , Kim Kwangsoo , Jeon Yoon Kyung , Chung Doo Hyun
Published: December 2024

Characteristics of patients with lung cancer treated with immune checkpoint inhibitor (immunohistochemistry cohort)
Figure S2 from PTPRZ1-Targeting RNA CAR T Cells Exert Antigen-Specific and Bystander Antitumor Activity in Glioblastoma
Authors: Martinez Bedoya Darel , Marinari Eliana , Davanture Suzel , Castillo Cantero Luis , Erraiss Sarah , Dockerill Millicent , Barluenga Sofia , Winssinger Nicolas , Schaller Karl , Bijlenga Philippe , Momjian Shahan , Voize Christel , Tissot Stéphanie R. , Kandalaft Lana E. , Hammel Philippe , Cosson Pierre , Walker Paul R. , Dutoit Valérie , Migliorini Denis
Published: December 2024

Anti-PTPRZ1 CAR-T cell effector function after incubation with the Ge1302_PTPRZ1-KI cells
Figure S4 from Hyper-Interferon Sensitive Influenza Induces Adaptive Immune Responses and Overcomes Resistance to Anti–PD-1 in Murine Non–Small Cell Lung Cancer
Authors: Du Yushen , Salehi-Rad Ramin , Zhang Tian-hao , Crosson William P. , Abascal Jensen , Chen Dongdong , Shi Yuan , Jiang Hong , Tseng Yen-Wen , Ma Xi , Hong Mengying , Wang Sihan , Wang Xijuan , Tang Kejun , Hu Shiyao , Li Yuting , Ni Shaokai , Cai Yiqi , Tappuni Shahed , Shen Yong , Liu Bin , Sun Ren
Published: December 2024

Gating strategy for flow cytometry and supplementary flow and scRNA-seq data
Data from CD91 and Its Ligand gp96 Confer Cross-Priming Capabilities to Multiple APCs during Immune Responses to Nascent, Emerging Tumors
Authors: Nayak Devanshi A. , Sedlacek Abigail L. , Cillo Anthony R. , Watkins Simon C. , Binder Robert J.
Published: December 2024

Abstract
During cancer immunosurveillance, dendritic cells (DC) play a central role in orchestrating T-cell responses against emerging tumors. Capture of miniscule amounts of antigen along with tumor-initiated costimulatory signals can drive maturation of DCs. Expression of CD91 on DCs is essential in cross-priming of T-cell responses in the context of nascent tumors. Multiple DC and macrophage subsets express CD91 and engage tumor-derived gp96 to initiate antitumor immune responses, yet the specific CD91+ antigen-presenting cells (APC) that are required for T-cell cross-priming during cancer immunosurveillance are unknown. In this study, we determined that CD91 expression on type 1 conventional DCs (cDC1) is necessary for cancer immunosurveillance. Specifically, CD91-expressing cDC1 were found to capture the CD91 ligand gp96 from tumors and, upon migration to the lymph nodes, distribute gp96 among lymph node–resident APCs. However, cDC1 that captured tumor-derived gp96 only provided early tumor control, whereas sustained and long-term tumor rejection was bestowed to the host by other gp96+ cross-priming DCs. We further found that the CD91-induced transcriptome in APCs promoted cross-priming of T-cell responses while downregulating immune regulatory pathways. Our results show an elaborate and synchronized division of labor of APCs in the successful elimination of cancer cells via CD91. We predict that the specialized functions of APC subsets can be harnessed for immunotherapy of disease.
Data from Peripheral Blood–Derived PD-1/CD28–CD19 CAR–Modified PD-1+ T-Cell Therapy in Patients with Solid Tumors
Authors: Zhang Zhen , Zhao Xuan , Zhao Qitai , Chen Xinfeng , Li Congcong , Liu Yaqing , Shen Chunyi , Song Lijie , Miao Lijun , Guo Fuyou , Mou Xiaoning , Zhao Jie , Gu Weiyue , Zhang Yi
Published: December 2024

Abstract
T cells expressing programmed cell death 1 (PD-1) in the peripheral blood (PB) of patients with tumors possess therapeutic potential; however, the immunosuppressive, PD-1–triggered signaling pathway and limited proliferative capacity of PD-1+ T cells present challenges to their therapeutic application. Here, we observed no discernible distinction between PD-1+ and PD-1− T cells in terms of clonal overlap. However, CD8+PD-1+ T cells from PB and tumor tissues exhibited tighter clustering based on clone size. Single-cell RNA sequencing analysis showed that PD-1+ T cells from PB highly expressed cytotoxicity-related genes and were enriched for T-cell activation–related pathways compared with PD-1− T cells from PB or tumor tissues. Consistent with this, PB-derived PD-1+ T cells exhibited strong cytotoxicity toward autologous tumor cells and tumor cell lines. To augment PD-1+ T-cell activity against solid tumors in vivo, we introduced a PD-1/CD28 fusion receptor combined with a CD19 chimeric antigen receptor into PD-1+ T cells, which were then expanded in vitro. The modified PD-1+ T cells exhibited superior proliferation and antitumor abilities in vitro. In addition, four patients with cancer were infused with autologous PD-1/CD28–CD19 chimeric antigen receptor PD-1+ T cells. None of these patients experienced severe side effects, and one patient with melanoma achieved a complete response that was maintained for 6.7 months. The three other patients had stable disease. Collectively, these results suggested that cell therapy with modified PB-derived PD-1+ T cells is both safe and effective, and it may constitute a promising treatment strategy for patients with cancer.
Data from Spatially Resolved Whole-Transcriptomic and Proteomic Profiling of Lung Cancer and Its Immune Microenvironment According to PD-L1 Expression
Authors: Koh Jaemoon , Lee Dongjoo , Kim Sehui , Song Seung Geun , Han Bogyeong , Jeong Hyein , Kim Young A , Keam Bhumsuk , Lee Se-Hoon , Kim Kwangsoo , Jeon Yoon Kyung , Chung Doo Hyun
Published: December 2024

Abstract
The expression of PD-L1 on tumor cells (TC) is used as an immunotherapy biomarker in lung cancer, but heterogeneous intratumoral expression is often observed. To better understand heterogeneity in the lung cancer tumor microenvironment, we performed proteomic and whole-transcriptomic digital spatial profiling analyses of TCs and immune cells (IC) in spatially matched areas based on tumor PD-L1 expression and the status of the immune microenvironment. We validated our findings using IHC, data from The Cancer Genome Atlas, and immunotherapy cohorts. ICs in areas with high PD-L1 expression on TCs showed more features, indicative of immunosuppression and exhaustion, than ICs in areas with low PD-L1 expression on TCs. TCs highly expressing PD-L1 within immune-inflamed areas showed upregulation of proinflammatory processes, whereas TCs highly expressing PD-L1 within immune-deficient areas showed upregulation of various metabolic processes. Using differentially expressed genes of TCs between the immune-inflamed and immune-deficient areas, we identified a prognostic gene signature for lung cancer. In addition, we found that a high ratio of CD8+ cells to M2 macrophages predicted favorable outcomes in patients with PD-L1–expressing lung cancer after immune checkpoint inhibitor therapy. Overall, this study demonstrates that TCs and ICs have distinct spatial features within the lung tumor microenvironment that are related to tumor PD-L1 expression and IC infiltration.
ESCAPE study: Cannabidiol use in patients treated for substance use disorders, prevalence of use and characteristics of users.
Authors: Duval Mélanie , Istvan Marion , Rousselet Morgane , Laforgue Edouard-Jules , Grall-Bronnec Marie , Mauriat Claire , Victorri-Vigneau Caroline
Published: December 2024

Introduction: Cannibidiol (CBD) is one of the two primary phytocannabinoids found in cannabis. Its diverse pharmacological properties suggest potential benefits for a wide range of medical conditions. The primary objective of this study was to estimate the prevalence of CBD use among patients being treated for substance use disorder. Additionally, we aimed to characterize the pattern of CBD use and describe the profiles of users.
Methods: Patients admitted to two substance use disorder departments between May 6, 2020, and July 23, 2021were included in the study. Sociodemographic, medical and substance use data, including CBD use, were collected. A multiple correspondence analysis (MCA) was performed to identify substance uses most frequently correlated with CBD use. Multivariate analyses were also conducted to identify factors associated with CBD use.
Results: The prevalence of CBD use in the past 12 months among the 183 patients was 38.2%. However, at the time of the study, 63% had stopped using CBD, primarily due to its perceived ineffectiveness and cost. CBD was commonly consumed via inhalation, either by smoking the plant or using e-cigarette liquids. The MCA revealed that while there is no typical profile of CBD users, they were more likely to use sedative substances rather than stimulants. CBD users were younger and more likely to have psychiatric comorbidities.
Conclusion: The prevalence of CBD use was notably high. Given the significant risk of drug interactions with CBD and its wide variability in composition, it is crucial for clinicians to routinely inquire about CBD use. The potential for self-therapeutic or recreational use in these patients appears to be underestimated.
Engagement in the Community-Based Going-Out Programs and the Association with Physical Frailty Assessed by the Kihon Checklist: A Cohort Study
Authors: Morikawa Masanori , Harada Kenji , Kurita Satoshi , Nishijima Chiharu , Fujii Kazuya , Kakita Daisuke , Yamashiro Yukari , Takayanagi Naoto , Sudo Motoki , Shimada Hiroyuki
Published: December 2024

Introduction: In efforts to address the public health concern of physical frailty prevention, community-based programs without supervision are anticipated, yet efficacy has not been shown. We aimed to investigate the association of engaging in an unsupervised, community-based going-out program on the incidence of physical frailty among older adults. Methods: A cohort observational study was employed. Following a baseline assessment during 2015 and 2017 in Japan, we observed 1,350 older adults engage in a community-based going-out program for 12 months. Participants were categorized into either a non-engaged or engaged group via propensity score matching. A follow-up survey (mean period = 920 ± 76 days) was conducted to investigate the occurrence of physical frailty using the Kihon Checklist. The incidence of frailty, absolute risk reduction, and number needed to treat for program engagement were calculated. The odds ratio (OR) in engaged group compared with the non-engaged group was determined in a logistic regression model. Results: Incidence of frailty was 15.1% in non-engaged group (n = 107 out of 628) and 8.3% in the engaged group (n = 53 out of 628). The number needed to treat and its 95% confidence interval were 21 (12–63) after matching. Compared with matched non-engaged group (OR 1.0), the OR and 95% confidence interval of matched engaged group for occurrence of physical frailty were 0.61 (0.42–0.87). Conclusions: Engaging in the unsupervised community-based going-out program could prevent one incidence of physical frailty in every 21 participants and may thus contribute to preventing physical frailty at the population level.
Biologics Use for Psoriasis during Pregnancy and Its Related Adverse Outcomes in Pregnant Women and Newborns: Findings from WHO Pharmacovigilance Study
Authors: Jeong Yi Deun , Jo Hyesu , Cho Hanseul , Jang Wonwoo , Park Jaeyu , Lee Sooji , Lee Hayeon , Lee Kyeongmin , Oh Jiyeon , Wen Xuerong , Smith Lee , Yon Dong Keon
Published: December 2024

Introduction: The safety of biologics, other than TNF-α inhibitors, during pregnancy has not been sufficiently established. To assess the risk of pregnancy-related adverse outcomes of biologics used for psoriasis, compared to TNF-α inhibitors, we utilized the WHO global pharmacovigilance database (1968–2024). Methods: We utilized the World Health Organization’s global pharmacovigilance database from 1968 to 2024. From over 140 million reports from more than 170 countries, we extracted 6,518 reports of pregnancy-related adverse outcomes associated with the biologics of interest. These biologics included TNF-α inhibitors (e.g., etanercept, infliximab, adalimumab, certolizumab pegol), IL-12/IL-23 inhibitor (e.g., ustekinumab), IL-17 inhibitors (e.g., secukinumab, brodalumab, ixekizumab, bimekizumab), and IL-23 inhibitors (e.g., guselkumab, tildrakizumab, risankizumab). Each biologic was compared to TNF-α inhibitors and certolizumab pegol in two separate disproportionality analyses. The reporting odds ratio (ROR) was calculated for maternal, fetal, and neonatal outcomes, categorized into seven major groups. Multivariable and sensitivity analyses were conducted to validate the primary results. Results: The disproportionality analysis showed that, compared to TNF-α inhibitors, most biologics had a lower frequency of pregnancy-related adverse outcomes, with the exception of brodalumab. Specifically, ROR and 95% confidence intervals (CIs) were as follows: ustekinumab (ROR, 0.27; 95% CI: 0.21–0.35), secukinumab (0.17; 0.13–0.22), brodalumab (0.20; 0.02–2.21), ixekizumab (0.05; 0.03–0.08), bimekizumab (0.10; 0.01–0.71), guselkumab (0.09; 0.05–0.15), tildrakizumab (0.02; 0.00–0.14), and risankizumab (0.38; 0.25–0.58). However, risankizumab was reported with a higher frequency of abortion and stillbirth (1.87; 1.32–2.63). These findings were consistent when compared to certolizumab pegol, as well as in multivariable and sensitivity analyses. Furthermore, when comparing other TNF-α inhibitors to certolizumab pegol, infliximab showed a lower frequency of pregnancy-related adverse outcomes (ROR, 0.71; 95% CI: 0.55–0.92), etanercept showed a comparable frequency (1.00; 0.77–1.31), and adalimumab showed a higher frequency (1.42; 1.11–1.81). Conclusions: Biologics used for psoriasis, with the exception of brodalumab, exhibit a lower frequency of pregnancy-related adverse outcomes compared to TNF-α inhibitors and certolizumab pegol, suggesting their potential to be safe options during pregnancy. However, further studies are necessary to evaluate the safety of these biologics during pregnancy, accounting for confounding factors.
Effects of Cacna1d D307G Mutation on Blood Pressure and Kidney Function in Rats with Salt Loading
Authors: Cheng Lan , Chen Hui , Maboh R. Nfornah , Wang Huan
Published: December 2024

Introduction: Our recent findings revealed that CACNA1D D307G mutation participates in the early-onset hypertension. Methods: We used the CRISPR/Cas9 technique to generate the Cacna1d D307G mutation rat model and investigated the effects of Cacna1d D307G mutation on blood pressure (BP) and renal function. Rats fed normal-salt diet had normal plasma aldosterone levels but higher plasma ET-1 and mildly elevated systolic BP (SBP) in D307G and G307G rats compared with the wild type (WT) until 24 weeks. Renal function and renal histopathology did not significantly differ among the three groups. Results: When fed high-salt diet (HSD), D307G and G307G rats showed more sensitivity to HSD. The results showed a further increase in SBP than in WT rats. Plasma and vascular endothelin-1 (ET-1) level and cortex and renal artery endothelin type A (ETA) receptor protein expression were significantly increased. Enhanced renal injury was also noted as indicated by an increased ratio of kidney weight/body weight, elevated urinary protein and albumin/creatinine ratio, higher kidney injury molecule-1 (KIM-1) levels, advanced fibrosis and apoptosis, and inflammation. Further experiments revealed a reduction in urinary sodium excretion and creatinine clearance. Higher protein expression of renal cortex epithelial sodium channel α subunit (αENaC) was confirmed in D307G and G307G rats fed HSD. However, a selective ETA receptor blockade (ABT-627) could partially reverse the increased SBP, increased serum KIM-1 level, upregulated renal cortex protein expression of αENaC, and reduced urinary sodium excretion with reduced creatinine clearance in D307G rats fed HSD. Conclusion: Activation of the ET-1/ETA system in D307G mutation rats might have contributed to increased sensitivity to salt loading, augmented hypertension, and exacerbated the renal injury.
Prevalence of and factors Influencing Oral Health Behaviours in 2-Year-Old Children: a cross-sectional analysis of data from the KUNO-Kids health study
Authors: Lennon Áine M. , Musiol Christoph , Hiller Karl-Anton , Gade Nils , Buchalla Wolfgang , Brandstetter Susanne , Körninger Angela , Melter Michael , Apfelbacher Christian , Kabesch Michael ,   the KUNO-Kids Study Group
Published: December 2024

Introduction: This questionnaire-based investigation aimed to assess Oral Health Behaviour (OHB) in 2-year-old children taking part in a birth cohort study and to identify relationships between general health, socioeconomic as well as psychosocial factors and OHB. Methods: Factors examined were single parent status, migration background, child’s sex, parity, maternal age, education and social support, paternal employment, parental mental and physical health and child health, data for which were collected at birth, 4 weeks, or 1 year. Participants who answered all OHB questions at 2-years (n=730) were included. Nutritional score (NS), tooth brushing score (TS), and dental check-up score (CS) were used to calculate overall OHB score. Results: Overall OHB in this cohort was good. 62% ate fruit or vegetables daily, 75% brushed 2-3 times daily and 61% had already had a dental check-up. Children of single-mothers had significantly lower OHB scores. NS was significantly higher for children with migration background, children of mothers with better physical health or higher educational level, but lower for children of mothers reporting poor social support. TS was significantly lower in children of single-mothers and children of fathers reporting poorer mental health. CS was significantly higher in children of multiparous mothers. This study highlights the relevance of social support and parental health, in contributing to OHB patterns. Conclusion: Families with special healthcare needs or less robust social support may have difficulty maintaining good OHB.
Serum Neurofilament Light-Chain Levels in Essential Tremor: A Replication Study
Authors: Louis Elan D. , Sharma Vibhash D. , Hajjar Ihab , Hernandez Nora
Published: December 2024

Introduction: Essential tremor (ET) is a highly-prevalent neurological disease. At present, there are no clinical biomarkers. Neurofilament light (NfL) has been studied as a measure of neuronal damage in a considerable number of neurological disorders. There have been three studies of ET, and results are inconsistent.
Methods: 40 ET cases were enrolled in a research study between February and November 2023 and compared to two control groups from Study 1 (n = 41) and Study 2 (n = 185). Total tremor score was a measure of the severity of action tremor. Blood samples were analyzed for serum NfL level on the Simoa® platform using an NF-Light™ kit as a marker of axonal injury.
Results: Serum log NfL levels were higher in ET cases than controls in Study 1 (p<0.001) and Study 2 (p<0.001). In a multivariate linear regression model, ET cases (p = 0.03) and individuals of older age (p<0.001) had higher serum log NfL levels than controls (combined in Studies 1 and 2). There was no association in ET cases between serum log NfL level and total tremor score (Pearson’s r = 0.08, p = 0.63).
Conclusion: This new study further validates the elevation in serum NfL levels in ET, now representing the third study to do so. In combination, the converging data suggest that there is an overall increase in serum NfL levels in ET. The demonstration of elevated serum levels of NfL in ET adds an additional piece of evidence that there is neuronal damage in ET.
A indústria brasileira de private equity: Market timing para desinvestimento pós IPO
Authors: Vieira Tássio Araújo , Botelho Ducineli Regis , Ribeiro Alex Mussoi , Dantas José Alves
Published: December 2024

This is a descriptive, quantitative study that used as a database information from Equity Investment Funds (EIF) and records of 49 companies supported by Private Equity (PE) and Venture Capital (VC) in Brazil, between the years 2000 and 2020, which carried out an IPO and were fully divested. The results show that 2.7 years is the approximate time for total divestment - close to the 3 years of the US market, in addition to the fact that when the shares held by the PE/VC Funds were fully divested, the prices of the shares were higher than the prices at the IPO and, finally, that the exits resulted in positive abnormal returns for investors. Therefore, this study brings contributions to society and to the Applied Social Sciences, as it is innovative in measuring the Market Timing of divestment in the PE/VC industry in Brazil, as well as filling a gap in the internal literature and perhaps assisting researchers interested in further exploring this subject.
Efeito da colaboração na relação entre troca social e desenho do sistema de controle gerencial
Authors: Anzilago Marcielle , Lunkes Rógerio João
Published: December 2024

O estudo tem como objetivo analisar o efeito mediador da colaboração nas trocas sociais entre gestores no desenho do sistema de controle gerencial. Realizou-se um estudo descritivo com abordagem quantitativa por meio de uma survey, para tal utilizou-se um questionário. A população é formada por 423 empresas listadas na Brasil, Bolsa, Balcão (B3). O instrumento de pesquisa foi enviado aos gestores por meio da plataforma SurveyMonkey. A amostra final totalizou 203 respondentes. Para a análise dos dados utilizou-se a modelagem de equações estruturais (MEE). Propagação da importância de contextos comportamentais, psicológicos e sociais, com o intuito de melhorar o relacionamento entre as organizações e gestores, e consequentemente melhorar o desenho do SCG, contribuindo no desempenho organizacional. Os resultados mostram relações diretas positivas e significativas entre as trocas sociais e o desenho do SCG. Os resultados também indicam que a colaboração possui efeito mediador entre as trocas sociais entre gestores e o desenho do SCG. O estudo contribui para a literatura ao abarcar os conceitos da SET em um novo campo de pesquisa, assim, apresenta resultados consistentes e amplia o arcabouço da Teoria e do SCG.
A alimentação na idade escolar e pre-escolar
Authors: Almeida Junior A.
Published: December 2024

A pratica da alimentação tem, por emquanto, semelhanças com a politicagem de aldeia: orientam-n'a o habito, as conveniencias, as sympathias de cada um e envolve-a pesada atmosphera sentimental que leva estes a dizer verrinas contra a carne; aquelles, a tecer-lhe dythirambos; uns, a pregar a boa mesa, em que se come á tripa forra; outros, a clamar pela frugalidade c pelo jejum periodico. De vez em quando, surgem advogados da ahobora, apostolos do limão, cavalleiros andantes da cebola, apontando os seus ídolos como exclusivos merecedores de nosso culto e dos nossos dentes. E os ídolos. repentinamente, mergulham no esquecimento. Não se diga que estas paixões alimentares médram apenas entre os profanos: pesados linos de sciencia consignam taes exageros e perpetuam as dissenções romanticas entre a carne e o vegetal, entre o jejum e a abundancia.
O Estado de São Paulo e alguns de seus serviços de saude publica
Authors: Souza G. H. de Paula
Published: December 2024

Não faremos um resumo historico ou retrospecto da creação e progressivo desenvolvimento dos serviços de saude publica no Estado de S.Paulo, porque o nosso desideratum não é precisamente esse, mas se traduz tão somente na simples exposição de como se encontram alguns dentre elles actualmente, qual o seu funccionamento e qual a orientação administrativa a que obedecem, desde 1891, quando foram organizados pela lei n." 12, de outubro desse anno.