bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Figure S3 from Olaparib plus Durvalumab, with or without Bevacizumab, as Treatment in PARP Inhibitor-Naïve Platinum-Sensitive Relapsed Ovarian Cancer: A Phase II Multi-Cohort Study
Authors: Drew Yvette , Kim Jae-Weon , Penson Richard T. , O'Malley David M. , Parkinson Christine , Roxburgh Patricia , Plummer Ruth , Im Seock-Ah , Imbimbo Martina , Ferguson Michelle , Rosengarten Ora , Steeghs Neeltje , Kim Min Hwan , Gal-Yam Einav , Tsoref Daliah , Kim Jae-Hoon , You Benoit , De Jonge Maja , Lalisang Roy , Gort Eelke , Bastian Sara , Meyer Kassondra , Feeney Laura , Baker Nigel , Ah-See Mei-Lin , Domchek Susan M. , Banerjee Susana
Published: January 2024

Individual patient outcomes in the (A) non-gBRCAm doublet cohort and (B) non-gBRCAm triplet cohort
Supplementary Table S5 from Proteomic Profiling of Advanced Melanoma Patients to Predict Therapeutic Response to Anti-PD-1 Therapy
Authors: Zila Nina , Eichhoff Ossia M. , Steiner Irene , Mohr Thomas , Bileck Andrea , Cheng Phil F. , Leitner Alexander , Gillet Ludovic , Sajic Tatjana , Goetze Sandra , Friedrich Betty , Bortel Patricia , Strobl Johanna , Reitermaier René , Hogan Sabrina A. , Martínez Gómez Julia M. , Staeger Ramon , Tuchmann Felix , Peters Sophie , Stary Georg , Kuttke Mario , Elbe-Bürger Adelheid , Hoeller Christoph , Kunstfeld Rainer , Weninger Wolfgang , Wollscheid Bernd , Dummer Reinhard , French Lars E. , Gerner Christopher , Aebersold Ruedi , Levesque Mitchell P. , Paulitschke Verena
Published: January 2024

Statistical analysis of baseline clinical parameters in the independent Zurich serum validation cohort A (n=80).
Supplementary Table S4 from Proteomic Profiling of Advanced Melanoma Patients to Predict Therapeutic Response to Anti-PD-1 Therapy
Authors: Zila Nina , Eichhoff Ossia M. , Steiner Irene , Mohr Thomas , Bileck Andrea , Cheng Phil F. , Leitner Alexander , Gillet Ludovic , Sajic Tatjana , Goetze Sandra , Friedrich Betty , Bortel Patricia , Strobl Johanna , Reitermaier René , Hogan Sabrina A. , Martínez Gómez Julia M. , Staeger Ramon , Tuchmann Felix , Peters Sophie , Stary Georg , Kuttke Mario , Elbe-Bürger Adelheid , Hoeller Christoph , Kunstfeld Rainer , Weninger Wolfgang , Wollscheid Bernd , Dummer Reinhard , French Lars E. , Gerner Christopher , Aebersold Ruedi , Levesque Mitchell P. , Paulitschke Verena
Published: January 2024

Statistical analysis of baseline clinical parameters in the serum discovery cohort (n=56).
Supplementary Table S3 from Proteomic Profiling of Advanced Melanoma Patients to Predict Therapeutic Response to Anti-PD-1 Therapy
Authors: Zila Nina , Eichhoff Ossia M. , Steiner Irene , Mohr Thomas , Bileck Andrea , Cheng Phil F. , Leitner Alexander , Gillet Ludovic , Sajic Tatjana , Goetze Sandra , Friedrich Betty , Bortel Patricia , Strobl Johanna , Reitermaier René , Hogan Sabrina A. , Martínez Gómez Julia M. , Staeger Ramon , Tuchmann Felix , Peters Sophie , Stary Georg , Kuttke Mario , Elbe-Bürger Adelheid , Hoeller Christoph , Kunstfeld Rainer , Weninger Wolfgang , Wollscheid Bernd , Dummer Reinhard , French Lars E. , Gerner Christopher , Aebersold Ruedi , Levesque Mitchell P. , Paulitschke Verena
Published: January 2024

Differentially expressed proteins (DEPs) in NR of the discovery serum and tumor cell cohorts.
Supplementary Figure 1 from A Phase II Trial of the CD40 Agonistic Antibody Sotigalimab (APX005M) in Combination with Nivolumab in Subjects with Metastatic Melanoma with Confirmed Disease Progression on Anti-PD-1 Therapy
Authors: Weiss Sarah A. , Sznol Mario , Shaheen Montaser , Berciano-Guerrero Miguel-Ángel , Couselo Eva Muñoz , Rodríguez-Abreu Delvys , Boni Valentina , Schuchter Lynn M. , Gonzalez-Cao Maria , Arance Ana , Wei Wei , Ganti Apar Kishor , Hauke Ralph J. , Berrocal Alfonso , Iannotti Nicholas O. , Hsu Frank J. , Kluger Harriet M.
Published: January 2024

Peripheral blood studies
Supplementary Data 1 from A Phase II Trial of the CD40 Agonistic Antibody Sotigalimab (APX005M) in Combination with Nivolumab in Subjects with Metastatic Melanoma with Confirmed Disease Progression on Anti-PD-1 Therapy
Authors: Weiss Sarah A. , Sznol Mario , Shaheen Montaser , Berciano-Guerrero Miguel-Ángel , Couselo Eva Muñoz , Rodríguez-Abreu Delvys , Boni Valentina , Schuchter Lynn M. , Gonzalez-Cao Maria , Arance Ana , Wei Wei , Ganti Apar Kishor , Hauke Ralph J. , Berrocal Alfonso , Iannotti Nicholas O. , Hsu Frank J. , Kluger Harriet M.
Published: January 2024

Representativeness of Study Participants
Supplementary Figure S4 from Phase II Clinical Trial of Pembrolizumab and Chemotherapy Reveals Distinct Transcriptomic Profiles by Radiologic Response in Metastatic Triple-Negative Breast Cancer
Authors: Wilkerson Avia D. , Parthasarathy Prerana Bangalore , Stabellini Nickolas , Mitchell Carley , Pavicic Paul G. , Fu Pingfu , Rupani Amit , Husic Hana , Rayman Patricia A. , Swaidani Shadi , Abraham Jame , Budd G. Thomas , Moore Halle , Al-Hilli Zahraa , Ko Jennifer S. , Baar Joseph , Chan Timothy A. , Alban Tyler , Diaz-Montero C. Marcela , Montero Alberto J.
Published: January 2024

Differential IGHG1 expression between the IGHG1high (highest tertile) versus IGHG1low (lower tertiles) groups
Supplementary Figure S3 from Phase II Clinical Trial of Pembrolizumab and Chemotherapy Reveals Distinct Transcriptomic Profiles by Radiologic Response in Metastatic Triple-Negative Breast Cancer
Authors: Wilkerson Avia D. , Parthasarathy Prerana Bangalore , Stabellini Nickolas , Mitchell Carley , Pavicic Paul G. , Fu Pingfu , Rupani Amit , Husic Hana , Rayman Patricia A. , Swaidani Shadi , Abraham Jame , Budd G. Thomas , Moore Halle , Al-Hilli Zahraa , Ko Jennifer S. , Baar Joseph , Chan Timothy A. , Alban Tyler , Diaz-Montero C. Marcela , Montero Alberto J.
Published: January 2024

Genes associated with response to CNPs
Supplementary Figure S2 from Phase II Clinical Trial of Pembrolizumab and Chemotherapy Reveals Distinct Transcriptomic Profiles by Radiologic Response in Metastatic Triple-Negative Breast Cancer
Authors: Wilkerson Avia D. , Parthasarathy Prerana Bangalore , Stabellini Nickolas , Mitchell Carley , Pavicic Paul G. , Fu Pingfu , Rupani Amit , Husic Hana , Rayman Patricia A. , Swaidani Shadi , Abraham Jame , Budd G. Thomas , Moore Halle , Al-Hilli Zahraa , Ko Jennifer S. , Baar Joseph , Chan Timothy A. , Alban Tyler , Diaz-Montero C. Marcela , Montero Alberto J.
Published: January 2024

Heat map of Hallmark Pathway Enrichment for each pairwise comparison of radiographic response category (CR, PR, SD, PD)
Supplementary Figure S1 from PHF6-altered T-ALL Harbor Epigenetic Repressive Switch at Bivalent Promoters and Respond to 5-Azacitidine and Venetoclax
Authors: Pinton Antoine , Courtois Lucien , Doublet Charlotte , Cabannes-Hamy Aurélie , Andrieu Guillaume , Smith Charlotte , Balducci Estelle , Cieslak Agata , Touzart Aurore , Simonin Mathieu , Lhéritier Véronique , Huguet Françoise , Balsat Marie , Dombret Hervé , Rousselot Philippe , Spicuglia Salvatore , Macintyre Elizabeth , Boissel Nicolas , Asnafi Vahid
Published: January 2024

Supplementary Figure 1
(A) Circos plot representing mutations co-occurrences in PHF6WT (left) and PHF6ALT T-ALL (right). (B) Variant allele frequencies (VAF) of mutations at diagnosis and relapse. Genes are ordered by decreasing VAF at diagnosis from left to right.
Data from A Fully Automated Deep-Learning Model for Predicting the Molecular Subtypes of Posterior Fossa Ependymomas Using T2-Weighted Images
Authors: Cheng Dan , Zhuo Zhizheng , Du Jiang , Weng Jinyuan , Zhang Chengzhou , Duan Yunyun , Sun Ting , Wu Minghao , Guo Min , Hua Tiantian , Jin Ying , Peng Boyang , Li Zhaohui , Zhu Mingwang , Imami Maliha , Bettegowda Chetan , Sair Haris , Bai Harrison X. , Barkhof Frederik , Liu Xing , Liu Yaou
Published: January 2024

AbstractPurpose:
We aimed to develop and validate a deep learning (DL) model to automatically segment posterior fossa ependymoma (PF-EPN) and predict its molecular subtypes [Group A (PFA) and Group B (PFB)] from preoperative MR images.
Experimental Design:
We retrospectively identified 227 PF-EPNs (development and internal test sets) with available preoperative T2-weighted (T2w) MR images and molecular status to develop and test a 3D nnU-Net (referred to as T2-nnU-Net) for tumor segmentation and molecular subtype prediction. The network was externally tested using an external independent set [n = 40; subset-1 (n = 31) and subset-2 (n =9)] and prospectively enrolled cases [prospective validation set (n = 27)]. The Dice similarity coefficient was used to evaluate the segmentation performance. Receiver operating characteristic analysis for molecular subtype prediction was performed.
Results:
For tumor segmentation, the T2-nnU-Net achieved a Dice score of 0.94 ± 0.02 in the internal test set. For molecular subtype prediction, the T2-nnU-Net achieved an AUC of 0.93 and accuracy of 0.89 in the internal test set, an AUC of 0.99 and accuracy of 0.93 in the external test set. In the prospective validation set, the model achieved an AUC of 0.93 and an accuracy of 0.89. The predictive performance of T2-nnU-Net was superior or comparable to that of demographic and multiple radiologic features (AUCs ranging from 0.87 to 0.95).
Conclusions:
A fully automated DL model was developed and validated to accurately segment PF-EPNs and predict molecular subtypes using only T2w MR images, which could help in clinical decision-making.
Data from Landscape of Clinical Resistance Mechanisms to FGFR Inhibitors in FGFR2-Altered Cholangiocarcinoma
Authors: Wu Qibiao , Ellis Haley , Siravegna Giulia , Michel Alexa G. , Norden Bryanna L. , Fece de la Cruz Ferran , Balasooriya Eranga Roshan , Zhen Yuanli , Silveira Vanessa S. , Che Jianwe , Corcoran Ryan B. , Bardeesy Nabeel
Published: January 2024

AbstractPurpose:
FGFR inhibitors are effective in FGFR2-altered cholangiocarcinoma, leading to approval of reversible FGFR inhibitors, pemigatinib and infigratinib, and an irreversible inhibitor, futibatinib. However, acquired resistance develops, limiting clinical benefit. Some mechanisms of resistance have been reported, including secondary FGFR2 kinase domain mutations. Here, we sought to establish the landscape of acquired resistance to FGFR inhibition and to validate findings in model systems.
Experimental Design:
We examined the spectrum of acquired resistance mechanisms detected in circulating tumor DNA or tumor tissue upon disease progression following FGFR inhibitor therapy in 82 FGFR2-altered cholangiocarcinoma patients from 12 published reports. Functional studies of candidate resistance alterations were performed.
Results:
Overall, 49 of 82 patients (60%) had one or more detectable secondary FGFR2 kinase domain mutations upon acquired resistance. N550 molecular brake and V565 gatekeeper mutations were most common, representing 63% and 47% of all FGFR2 kinase domain mutations, respectively. Functional studies showed different inhibitors displayed unique activity profiles against FGFR2 mutations. Interestingly, disruption of the cysteine residue covalently bound by futibatinib (FGFR2 C492) was rare, observed in 1 of 42 patients treated with this drug. FGFR2 C492 mutations were insensitive to inhibition by futibatinib but showed reduced signaling activity, potentially explaining their low frequency.
Conclusions:
These data support secondary FGFR2 kinase domain mutations as the primary mode of acquired resistance to FGFR inhibitors, most commonly N550 and V565 mutations. Thus, development of combination strategies and next-generation FGFR inhibitors targeting the full spectrum of FGFR2 resistance mutations will be critical.
Data from A Phase II Basket Trial of Dual Anti–CTLA-4 and Anti–PD-1 Blockade in Rare Tumors (DART SWOG 1609 Cohort 47) in Patients with Gestational Trophoblastic Neoplasia
Authors: Patel Sandip P. , Othus Megan , Chae Young Kwang , Dennis Michael J. , Gordon Sarah , Mutch David , Samlowski Wolfram , Robinson William R. “Rusty” , Sharon Elad , Ryan Christopher , Lopez Gabby , Plets Melissa , Blanke Charles , Kurzrock Razelle
Published: January 2024

AbstractPurpose:
The efficacy of immune checkpoint blockade in gestational trophoblastic neoplasia (GTN) remains uncertain. We report the results of the GTN cohort of SWOG S1609 dual anti–CTLA-4 and anti–PD-1 blockade in rare tumors (DART).
Patients and Methods:
This prospective, open-label phase II trial evaluated ipilimumab plus nivolumab across multiple rare tumor cohorts, including GTN. Eligible patients received nivolumab 240 mg, i.v. every 2 weeks and ipilimumab 1 mg/kg i.v. every 6 weeks. The primary endpoint was overall response rate [ORR; complete response (CR) + partial response (PR)] by quantitative serum beta human chorionic gonadotropin (β-hCG); secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity.
Results:
Four patients with refractory GTN enrolled and received therapy. At 11 months of ongoing follow-up, 3 of 4 patients responded [ORR = 75% (CR, 25%, n = 1, tumor mutation burden = 1 mutation/megabase; PD-L1 tumor proportion score = 50%); PR, 50%, n = 2)]. Responders included malignant gestational trophoblastic neoplasm (n = 1, CR, PFS 11+ months) and choriocarcinoma (n = 2, both PRs, PFS 10+ and 6+ months). One patient with epithelioid trophoblastic tumor experienced disease progression. The 6-month PFS was 75% [95% confidence interval (CI), 43%–100%], and the median PFS was not reached (range, 35–339+ days); all 4 patients were alive at last follow-up. Two patients experienced grade 3 immune-related toxicity (arthralgia and colitis); there were no grade ≥4 events.
Conclusions:
Ipilimumab plus nivolumab demonstrated efficacy in chemotherapy-refractory GTN, an ultra-rare cancer affecting young women. Three of 4 patients achieved ongoing objective responses with a reasonable safety profile at 6–11+ months.
Data from p31comet Induces Cellular Senescence through p21 Accumulation and Mad2 Disruption
Authors: Yun Miyong , Han Young-Hoon , Yoon Sun Hee , Kim Hee Young , Kim Bu-Yeo , Ju Yeun-Jin , Kang Chang-Mo , Jang Su Hwa , Chung Hee-Yong , Lee Su-Jae , Cho Myung-Haing , Yoon Gyesoon , Park Gil Hong , Kim Sang Hoon , Lee Kee-Ho
Published: January 2024

Abstract
Functional suppression of spindle checkpoint protein activity results in apoptotic cell death arising from mitotic failure, including defective spindle formation, chromosome missegregation, and premature mitotic exit. The recently identified p31comet protein acts as a spindle checkpoint silencer via communication with the transient Mad2 complex. In the present study, we found that p31comet overexpression led to two distinct phenotypic changes, cellular apoptosis and senescence. Because of a paucity of direct molecular link of spindle checkpoint to cellular senescence, however, the present report focuses on the relationship between abnormal spindle checkpoint formation and p31comet-induced senescence by using susceptible tumor cell lines. p31comet-induced senescence was accompanied by mitotic catastrophe with massive nuclear and chromosomal abnormalities. The progression of the senescence was completely inhibited by the depletion of p21Waf1/Cip1 and partly inhibited by the depletion of the tumor suppressor protein p53. Notably, p21Waf1/Cip1 depletion caused a dramatic phenotypic conversion of p31comet-induced senescence into cell death through mitotic catastrophe, indicating that p21Waf1/Cip1 is a major mediator of p31comet-induced cellular senescence. In contrast to wild-type p31comet, overexpression of a p31 mutant lacking the Mad2 binding region did not cause senescence. Moreover, depletion of Mad2 by small interfering RNA induced senescence. Here, we show that p31comet induces tumor cell senescence by mediating p21Waf1/Cip1 accumulation and Mad2 disruption and that these effects are dependent on a direct interaction of p31comet with Mad2. Our results could be used to control tumor growth. (Mol Cancer Res 2009;7(3):371–82)
Table S5 from Signaling Pathway Alterations Driven by BRCA1 and BRCA2 Germline Mutations are Sufficient to Initiate Breast Tumorigenesis by the PIK3CAH1047R Oncogene
Authors: Bhat-Nakshatri Poornima , Khatpe Aditi S. , Chen Duojiao , Batic Katie , Mang Henry , Herodotou Christopher , McGuire Patrick C. , Xuei Xiaoling , Erdogan Cihat , Gao Hongyu , Liu Yunlong , Sandusky George , Storniolo Anna Maria , Nakshatri Harikrishna
Published: January 2024

Table S5: Gene expression differences in epithelial cells, endothelial cells and fibroblasts of BRCA1 mutation carrier compared to BRCA2 mutation carrier.
Table S2 from Signaling Pathway Alterations Driven by BRCA1 and BRCA2 Germline Mutations are Sufficient to Initiate Breast Tumorigenesis by the PIK3CAH1047R Oncogene
Authors: Bhat-Nakshatri Poornima , Khatpe Aditi S. , Chen Duojiao , Batic Katie , Mang Henry , Herodotou Christopher , McGuire Patrick C. , Xuei Xiaoling , Erdogan Cihat , Gao Hongyu , Liu Yunlong , Sandusky George , Storniolo Anna Maria , Nakshatri Harikrishna
Published: January 2024

Number and percentage of different cell types in different tissue types used in this study.
Table S1 from Signaling Pathway Alterations Driven by BRCA1 and BRCA2 Germline Mutations are Sufficient to Initiate Breast Tumorigenesis by the PIK3CAH1047R Oncogene
Authors: Bhat-Nakshatri Poornima , Khatpe Aditi S. , Chen Duojiao , Batic Katie , Mang Henry , Herodotou Christopher , McGuire Patrick C. , Xuei Xiaoling , Erdogan Cihat , Gao Hongyu , Liu Yunlong , Sandusky George , Storniolo Anna Maria , Nakshatri Harikrishna
Published: January 2024

Information on samples used for single cell studies.
Figure S3 from Signaling Pathway Alterations Driven by BRCA1 and BRCA2 Germline Mutations are Sufficient to Initiate Breast Tumorigenesis by the PIK3CAH1047R Oncogene
Authors: Bhat-Nakshatri Poornima , Khatpe Aditi S. , Chen Duojiao , Batic Katie , Mang Henry , Herodotou Christopher , McGuire Patrick C. , Xuei Xiaoling , Erdogan Cihat , Gao Hongyu , Liu Yunlong , Sandusky George , Storniolo Anna Maria , Nakshatri Harikrishna
Published: January 2024

Expression levels of top transcription regulators in major epithelial subclusters (mature luminal/LHS, luminal progenitors/LASP and basal/BM cells).
Figure S1 from Signaling Pathway Alterations Driven by BRCA1 and BRCA2 Germline Mutations are Sufficient to Initiate Breast Tumorigenesis by the PIK3CAH1047R Oncogene
Authors: Bhat-Nakshatri Poornima , Khatpe Aditi S. , Chen Duojiao , Batic Katie , Mang Henry , Herodotou Christopher , McGuire Patrick C. , Xuei Xiaoling , Erdogan Cihat , Gao Hongyu , Liu Yunlong , Sandusky George , Storniolo Anna Maria , Nakshatri Harikrishna
Published: January 2024

Expression patterns of several epithelial cells enriched/specific genes in BRCA1 or BRCA2 mutation carriers compared to non-carrier.
FIGURE 5 from Signaling Pathway Alterations Driven by BRCA1 and BRCA2 Germline Mutations are Sufficient to Initiate Breast Tumorigenesis by the PIK3CAH1047R Oncogene
Authors: Bhat-Nakshatri Poornima , Khatpe Aditi S. , Chen Duojiao , Batic Katie , Mang Henry , Herodotou Christopher , McGuire Patrick C. , Xuei Xiaoling , Erdogan Cihat , Gao Hongyu , Liu Yunlong , Sandusky George , Storniolo Anna Maria , Nakshatri Harikrishna
Published: January 2024

Expression levels of previously described BL-enriched genes as well as those described to be enriched in breast epithelial cells of BRCA1 mutation carriers. A, Expression patterns of specific genes in cells from BRCA1 mutation carrier compared with non-carriers. Alveolar progenitor (AP) cell–enriched and BL cell–enriched genes are indicated. KIT expression is shown to mark LASP cells. Note a unique subpopulation within LASP cells that express higher levels of ALDH1A3 in BRCA1 mutation carriers. CALML5 and FAM3B are AP-enriched whereas SCGB2A2 and FXYD5 are BL-enriched genes. B, Expression patterns of specific genes in cells from BRCA2 mutation carriers compared with non-carriers.
FIGURE 4 from Signaling Pathway Alterations Driven by BRCA1 and BRCA2 Germline Mutations are Sufficient to Initiate Breast Tumorigenesis by the PIK3CAH1047R Oncogene
Authors: Bhat-Nakshatri Poornima , Khatpe Aditi S. , Chen Duojiao , Batic Katie , Mang Henry , Herodotou Christopher , McGuire Patrick C. , Xuei Xiaoling , Erdogan Cihat , Gao Hongyu , Liu Yunlong , Sandusky George , Storniolo Anna Maria , Nakshatri Harikrishna
Published: January 2024

Expression patterns of select genes in breast epithelial cells of BRCA1 and BRCA2 mutation carriers compared with non-carriers. LHS cells (based on ESR1, FOXA1, PGR, and GATA3 expression, black circle), LASP/alveolar cells (based on KIT and ELF5 expression, blue circle; Supplementary Fig. S1 for more details), and BM cell (based on TP63, ACTG2, MYL9, and OXTR expression, orange circle) populations are indicated. Note that CXCL13 expression is absent only in BRCA1 carrier-derived cells. MIR205HG expression was observed only in epithelial cells of BRCA1 and BRCA2 mutation carriers.
FIGURE 3 from Signaling Pathway Alterations Driven by BRCA1 and BRCA2 Germline Mutations are Sufficient to Initiate Breast Tumorigenesis by the PIK3CAH1047R Oncogene
Authors: Bhat-Nakshatri Poornima , Khatpe Aditi S. , Chen Duojiao , Batic Katie , Mang Henry , Herodotou Christopher , McGuire Patrick C. , Xuei Xiaoling , Erdogan Cihat , Gao Hongyu , Liu Yunlong , Sandusky George , Storniolo Anna Maria , Nakshatri Harikrishna
Published: January 2024

Comparison of breast epithelial cells of BRCA1 and BRCA2 mutation carriers with that of non-carriers. Breast epithelial cells were subclassified into BM, LASP, and LHS cells based on CD49f and EpCAM expression status as described previously (10). A, Side-by-side comparison of breast epithelial cells of BRCA1 mutation carriers with that of non-carriers. A distinct cluster of LASP cells is present only in non-carriers (indicated by an oval shape). B, Side-by-side comparison of breast epithelial cells of BRCA2 with that of non-carriers. Similar to BRCA1, a distinct cluster of LASP cells is present only in non-carriers. C, Side-by-side comparison of breast epithelial cells from BRCA1 mutation carriers with that of BRCA2 mutation carriers. D, Distribution pattern of BM, LASP, and LHS cells in non-carrier, BRCA1 and BRCA2 mutation carriers. E, Heat map showing top 10 genes highly expressed in cluster missing in BRCA1 and BRCA2 mutation carriers compared with other clusters.
Phase II Study of the Liposomal Formulation of Eribulin (E7389-LF) in Combination with Nivolumab: Results from the Small Cell Lung Cancer Cohort
Authors: Nishio Makoto , Murakami Shuji , Kawakami Hisato , Okishio Kyoichi , Tamiya Motohiro , Kobayashi Haruki , Fujimoto Daichi , Sugawara Shunichi , Kozuki Toshiyuki , Oya Yuko , Izumi Hiroki , Shiroyama Takayuki , Satouchi Miyako , Yamamoto Noboru , Kaname Shota , Matsuoka Daiko , Otake Yohei , Takase Takao , Semba Taro , Azuma Koichi
Published: January 2024

Purpose:

E7389-LF is a liposomal formulation of eribulin that contributes to tumor vascular remodeling. The phase II part of this phase Ib/II study assessed the efficacy/safety of E7389-LF in combination with nivolumab in several disease cohorts; herein, we report results from the small cell lung cancer (SCLC) cohort.

Experimental Design:

Patients with unresectable/measurable SCLC and disease progression with first-line platinum-based chemotherapy with/without an immune checkpoint inhibitor (ICI) were enrolled to receive E7389-LF 2.1 mg/m2 plus nivolumab 360 mg intravenously every 3 weeks. The primary objective of this part was to assess the objective response rate (ORR). Secondary objectives included assessments of safety and progression-free survival (PFS); exploratory assessments included overall survival (OS) and biomarkers.

Results:

Thirty-four patients were enrolled. By the data cut-off date (May 31, 2022), 29 (85.3%) had discontinued. Efficacy/biomarker analyses included 33 patients (1 had their diagnosis changed postenrollment); the ORR of E7389-LF plus nivolumab was 24.2% [95% confidence interval (CI): 11.1–42.3], the median PFS was 3.98 months (95% CI: 2.63–4.40), and, at a median follow-up of 10.6 months, the median OS was not reached (95% CI: not estimable). Notably, 27 of 33 patients (81.8%) had received an ICI as their prior first-line therapy. Treatment-related, treatment-emergent adverse events occurred in 97.1% (any grade) and 82.4% (grade ≥3) of enrolled patients; the most common event was neutropenia. Changes in vascular and immune-related plasma markers were observed.

Conclusions:

E7389-LF 2.1 mg/m2 in combination with nivolumab 360 mg every 3 weeks showed notable antitumor activity as second-line therapy for SCLC; no new safety signals were observed compared with either agent as monotherapy.

Significance:

This phase II part of a phase Ib/II study assessed liposomal eribulin (E7389-LF) plus nivolumab in 34 patients with pretreated SCLC; 8 of 33 evaluable patients (including 6/27 pretreated with ICIs) had objective responses. The combination was tolerable; increases in vasculature-related biomarkers tended to correlate with responses.
Neoadjuvant CD40 Agonism Remodels the Tumor Immune Microenvironment in Locally Advanced Esophageal/Gastroesophageal Junction Cancer
Authors: Soto Maira , Filbert Erin L. , Yang Hai , Starzinski Stephanie , Starzinski Alec , Gin Marissa , Chen Brandon , Le Phi , Li Tony , Bol Brandon , Cheung Alexander , Zhang Li , Hsu Frank J. , Ko Andrew , Fong Lawrence , Keenan Bridget P.
Published: January 2024

Sotigalimab is an agonistic anti-CD40 mAb that can modulate antitumor immune responses. In a phase II clinical trial of sotigalimab combined with neoadjuvant chemoradiation (CRT) in locally advanced esophageal/gastroesophageal junction (E/GEJ) cancer with the primary outcome of efficacy as measured by pathologic complete response (pCR) rate, the combination induced pCR in 38% of treated patients. We investigated the mechanism of action of sotigalimab in samples obtained from this clinical trial. Tumor biopsies and peripheral blood samples were collected at baseline, following an initial dose of sotigalimab, and at the time of surgery after CRT completion from six patients. High dimensional single-cell techniques were used, including combined single-cell RNA-sequencing and proteomics (CITEseq) and multiplexed ion beam imaging, to analyze immune responses. Sotigalimab dramatically remodeled the immune compartment in the periphery and within the tumor microenvironment (TME), increasing expression of molecules related to antigen processing and presentation and altering metabolic pathways in myeloid cells. Concomitant with these changes in myeloid cells, sotigalimab treatment primed new T cell clonotypes and increased the density and activation of T cells with enhanced cytotoxic function. Sotigalimab treatment also induced a decrease in the frequency of Tregs in the TME. These findings indicate that a single dose of sotigalimab leads to enhanced antigen presentation that can activate T cells and induce new T cell clones. This restructuring of the TME provides elements which are critical to the development of effective antitumor immune responses and improved clinical outcomes.
Revisitando a Síndrome de Down e sua história
Authors: Pietricoski Luciana Borowski , Justina Lourdes Aparecida Della
Published: January 2024

O objetivo deste trabalho é apresentar um panorama do percurso que levou ao esclarecimento da Síndrome de Down, principalmente a partir da segunda metade do século XX, no que diz respeito à sua caracterização e etiologia enquanto uma condição genética. Para isso, nos baseamos em fontes primárias e em fontes secundárias, levando também em conta os aspectos sociais envolvidos. Esta pesquisa mostra como o conhecimento sobre a Síndrome de Down foi sendo construído e seu impacto no tratamento pela sociedade, levando-a reconhecer os indivíduos com a síndrome a partir de uma condição genética e não como doentes. Esperamos que este estudo possa contribuir para a compreensão das ideias atuais sobre o assunto.
Dobzhansky and the Brazilians from his letters and reminiscences
Authors: Araújo Aldo Mellender de
Published: January 2024

Theodosius Dobzhansky (1900-1975) had an important role in the origin and development of evolutionary genetics in Brazil. Not only in 1943, when he had been here for the first time, about six months, but also in other moments, for more extended periods, he was responsible for the formation of the first generation of Drosophila geneticists with an emphasis on evolution, who later originated groups of research in evolutionary genetics in their respective states/countries. His relationship with three members of the 1943 group deserves special attention. Dobzhansky's relationship with André Dreyfus (1897-1952), at the time the head of the Department of General Biology at the University of São Paulo, was always respectful and friendly; with Crodowaldo Pavan (1919-2009), Dobzhansky was highly affectionate, although he was worried about the future of his most beloved disciple; Dobzhansky's relationship with Antonio Brito da Cunha (1925-2019) was one of admiration for his general culture and sophistication, however, it was less intense than with Pavan. Moreover, several members of his research team, from 1943 to 1956 deserved comments in his reminiscences (not always positive) for the Oral History of Columbia University, for more than 40 pages.
Gonçalves Dias e o episódio de Sordello da Commedia
Authors: Diniz Jackson da Silva , Nunes Margareth de Loudes Oliveira
Published: January 2024

Sabe-se que Gonçalves Dias preparava um volume com poemas traduzidos a que daria o nome de Ecos de Além-Mar (LEAL, 1867; PEREIRA, 2018). Talvez com esse objetivo tenha vertido A noiva de Messina, de Friedrich Schiller, e alguns poemas do francês, espanhol, italiano e sobretudo do alemão. Mas além desse projeto, parece que usava a reescritura como processo de aprendizagem linguístico e poética, estando nesse caso, segundo Leal (1867), a tradução para o português de parte do canto VI (versos 58-87, 97, 100-108, 112-126, 136-147, 149-151) da Divina Commedia, de Dante Alighieri, feita em 1844 quando estudava Direito em Coimbra. Trata-se da parte na qual Dante e Virgílio encontram o poeta lombardo Sordello e na qual há uma invectiva política. Este artigo possui dois objetivos, que se separem em tentar localizar a época da tradução do episódio pelo poeta maranhense, por um lado, e em comentar a reescritura, apontando, quando possível, possíveis motivações de escolha.
Pluriviolências em Negretta. Baci razzisti, de Marilena Delli Umuhoza
Authors: Fantinatti Tatiana
Published: January 2024

Nas obras literárias de escritoras italianas de origem africana evidenciam-se ao menos dois escopos: denunciar o racismo em todas as suas nuances e mostrar que o contato com culturas imigrantes enriquece as sociedades italianas. Neste trabalho abordo ambos, especialmente o primeiro. Através de personagens com características e vivências de suas próprias autoras ou de imigrantes da diáspora africana na Itália, revelam-se diversos tipos de racismo, que convocam a investigação em vários campos de estudo. Essa pluriviolência vindo à tona, enfada e desacomoda parte da sociedade que “ignora” o passado colonial italiano e o lastro que dele advém, pois aponta a escassez tanto de políticas públicas para minorias quanto de representatividades étnico-raciais. As relações entre as personagens da obra de ficção narrativa Negretta. Baci razzisti (2020), de Marilena Delli Umuhoza, escritora italiana de origem ruandesa, sinalizam como o colonialismo praticado por vários países deslegitimou as identidades dos corpos negros (RIBEIRO, 2019), seja nos vínculos entre personagens brancas e negras seja entre personagens negras entre si. Negretta traz o ponto de vista de uma personagem negra que enfrenta a violência racial em vários níveis institucionais na sociedade bergamasca, discriminatória e preconceituosa, nos anos 1990. Desvelando nano racismos (MBEMBE, 2016) “distraídos” e “inconscientes”, os quais perpetuam um humor generalizado sobre estereótipos absorvidos na normalidade ardilosa que mantém definida a separação racial, as personagens de Marilena Umuhoza revelam os danos morais padecidos pelo racismo institucional e pelo racismo recreativo (MOREIRA, 2019), gerando impactos em suas próprias realidades e na de seus descendentes.
Interhospital Variation in Admissions Managed With Critical Care Therapies or Invasive Hemodynamic Monitoring in Tertiary Cardiac Intensive Care Units: An Analysis From the Critical Care Cardiology Trials Network Registry
Authors: Donnelly Sarah , Barnett Christopher F. , Bohula Erin A. , Chaudhry Sunit-Preet , Chonde Meshe D. , Cooper Howard A. , Daniels Lori B. , Dodson Mark W. , Gerber Daniel , Goldfarb Michael J. , Guo Jianping , Kontos Michael C. , Liu Shuangbo , Luk Adriana C. , Menon Venu , O’Brien Connor G. , Papolos Alexander I. , Pisani Barbara A. , Potter Brian J. , Prasad Rajnish , Schnell Gregory , Shah Kevin S. , Sridharan Lakshmi , So Derek Y.F. , Teuteberg Jeffrey J. , Tymchak Wayne J. , Zakaria Sammy , Katz Jason N. , Morrow David A. , van Diepen Sean
Published: January 2024

BACKGROUND:

Wide interhospital variations exist in cardiovascular intensive care unit (CICU) admission practices and the use of critical care restricted therapies (CCRx), but little is known about the differences in patient acuity, CCRx utilization, and the associated outcomes within tertiary centers.

METHODS:

The Critical Care Cardiology Trials Network is a multicenter registry of tertiary and academic CICUs in the United States and Canada that captured consecutive admissions in 2-month periods between 2017 and 2022. This analysis included 17 843 admissions across 34 sites and compared interhospital tertiles of CCRx (eg, mechanical ventilation, mechanical circulatory support, continuous renal replacement therapy) utilization and its adjusted association with in-hospital survival using logistic regression. The Pratt index was used to quantify patient-related and institutional factors associated with CCRx variability.

RESULTS:

The median age of the study population was 66 (56–77) years and 37% were female. CCRx was provided to 62.2% (interhospital range of 21.3%–87.1%) of CICU patients. Admissions to CICUs with the highest tertile of CCRx utilization had a greater burden of comorbidities, had more diagnoses of ST–elevation myocardial infarction, cardiac arrest, or cardiogenic shock, and had higher Sequential Organ Failure Assessment scores. The unadjusted in-hospital mortality (median, 12.7%) was 9.6%, 11.1%, and 18.7% in low, intermediate, and high CCRx tertiles, respectively. No clinically meaningful differences in adjusted mortality were observed across tertiles when admissions were stratified by the provision of CCRx. Baseline patient-level variables and institutional differences accounted for 80% and 5.3% of the observed CCRx variability, respectively.

CONCLUSIONS:

In a large registry of tertiary and academic CICUs, there was a >4-fold interhospital variation in the provision of CCRx that was primarily driven by differences in patient acuity compared with institutional differences. No differences were observed in adjusted mortality between low, intermediate, and high CCRx utilization sites.
Idea or Concept? Progress in Comparative Methodological Perspective
Authors: Retz Tyson
Published: January 2024

The history of the idea of progress and the history of the concept of progress are two different things, not least because they emanate from considerably different intellectual traditions. In anglophone history of ideas, progress has typically been viewed as a belief. Historians of ideas explore the past evaluating the extent to which a given society met certain conditions of belief. By contrast, in the history of concepts as developed by Reinhart Koselleck, progress has occupied the dual role of a ‘basic concept’ that grasps modern sociopolitical reality and a ‘collective singular’ that aggregates previous and adjacent meanings in the one linguistic unit. This article compares these two historical research programmes, highlights their merits and deficiencies, and concludes by offering a new approach to the history of concepts as suggested by R.G. Collingwood’s theory of a scale of forms. In each of the approaches to the history of ideas and concepts addressed, particular attention is given to the problem of what qualifies as progress, and thus to a longstanding problem concerning the attribution of progress to past societies routinely excluded from its history, including those left out by Koselleck’s conventional secular-modern thesis.
The One Big Idea: Koselleck’s Structures of Repetition and Their Historiographical Consequences
Authors: Vogt Peter
Published: January 2024

What is the one big idea of Koselleck’s Historik understood as a methodological framework for the attempt to combine a theory of historical times with a theory of historical time? In part (1) of this paper, I criticize the two most basic attempts to understand Koselleck’s one big idea as mistaken because they are exclusively interested either in history (in the singular) or in histories (in the plural) and thus miss the central relevance of structures of repetition (“Wiederholungsstrukturen”) for Koselleck’s Historik. In part (2), I will clarify the rather hidden pre-history, the main ambition, the theoretical context and the substantial content of Koselleck’s concept of structures of repetition in history and language. In part (3), I will discuss four historiographical consequences of Koselleck’s structures of repetition. I will end the paper by observing a remarkable theoretical affinity between Barrington Moore’s search for recurring patterns in the field of sociology and Koselleck’s structures of repetition in history and language. Moore’s work illustrates the historiographical potential of the one big idea of Koselleck’s Historik better than any other work I am aware of.
The Search and Seizure of Digital Materials Under Warrant and Protecting Privilege: Comparative Analysis and Recommendations for Best Practice
Authors: Mitchell Rebecca , Stockdale Michael , Gilligan Francis A.
Published: January 2024

Academic literature in England and Wales and New Zealand does not consider the protection of legal professional privilege where digital material is seized under a search warrant. Academic literature in the United States does engage with this subject but is not informed by a comparative approach. This article fills both gaps. It examines practices that have been developed by investigative teams and prosecuting authorities in all three comparator jurisdictions in their attempts to provide safeguards necessary to preserve privilege. Such practices involve the use of technology to increase the speed, cost effectiveness and/or efficiency of identifying privileged documents. The process of developing these practices has been informed by judicial guidance, where they have been challenged before the courts, and by guidance from government departments, Bar Associations or Law Commissions. Following comparative analysis, the article recommends measures that should be included in legislation, codes of practice or guidance in any jurisdictions where there is potential for legal professional privilege or an equivalent concept to be undermined when digital material is seized under a search warrant.
Comparing Discrete Choice Experiment with Swing Weighting to Estimate Attribute Relative Importance: A Case Study in Lung Cancer Patient Preferences
Authors: Veldwijk J. , Smith I. P. , Oliveri S. , Petrocchi S. , Smith M. Y. , Lanzoni L. , Janssens R. , Huys I. , de Wit G. A. , Groothuis-Oudshoorn C. G. M
Published: January 2024

Introduction

Discrete choice experiments (DCE) are commonly used to elicit patient preferences and to determine the relative importance of attributes but can be complex and costly to administer. Simpler methods that measure relative importance exist, such as swing weighting with direct rating (SW-DR), but there is little empirical evidence comparing the two. This study aimed to directly compare attribute relative importance rankings and weights elicited using a DCE and SW-DR.

Methods

A total of 307 patients with non–small-cell lung cancer in Italy and Belgium completed an online survey assessing preferences for cancer treatment using DCE and SW-DR. The relative importance of the attributes was determined using a random parameter logit model for the DCE and rank order centroid method (ROC) for SW-DR. Differences in relative importance ranking and weights between the methods were assessed using Cohen’s weighted kappa and Dirichlet regression. Feedback on ease of understanding and answering the 2 tasks was also collected.

Results

Most respondents (>65%) found both tasks (very) easy to understand and answer. The same attribute, survival, was ranked most important irrespective of the methods applied. The overall ranking of the attributes on an aggregate level differed significantly between DCE and SW-ROC ( P < 0.01). Greater differences in attribute weights between attributes were reported in DCE compared with SW-DR ( P < 0.01). Agreement between the individual-level attribute ranking across methods was moderate (weighted Kappa 0.53–0.55).

Conclusion

Significant differences in attribute importance between DCE and SW-DR were found. Respondents reported both methods being relatively easy to understand and answer. Further studies confirming these findings are warranted. Such studies will help to provide accurate guidance for methods selection when studying relative attribute importance across a wide array of preference-relevant decisions.

Highlights

Both DCEs and SW tasks can be used to determine attribute relative importance rankings and weights; however, little evidence exists empirically comparing these methods in terms of outcomes or respondent usability. Most respondents found the DCE and SW tasks very easy or easy to understand and answer. A direct comparison of DCE and SW found significant differences in attribute importance rankings and weights as well as a greater spread in the DCE-derived attribute relative importance weights.
Alone as a drop, together as an ocean: Corporate political activity in cooperatives
Authors: Meneghini Eleandra Maria Prigol , Lana Jeferson , Gama Marina Amado Bahia , Marcon Rosilene
Published: January 2024

Cooperatives are formed by the collective efforts of various actors pursuing common goals, enabling competition with stronger rivals. In Brazil, there is a strong relationship between agricultural cooperatives and politics, with their involvement focused on competing for regulations, information, and access to capital. However, little is known about the effects of this involvement. In this paper, we draw on collective action theory to investigate the individual and collective corporate political activities adopted by Brazilian agricultural cooperatives. Corporate political activity (CPAs) are a subfield of nonmarket strategy (NMS) that addresses actions firms develop outside the market arena to improve their outcomes and achieve competitive advantage. This study focuses on CPAs of Brazilian agricultural cooperatives, which account for over 48% of national agricultural production. We argue that collective CPAs are more effective for these cooperatives, as they enhance their representativeness and legitimacy, facilitating access to capital. To support our argument, we conducted a quantitative study using panel data from 394 Brazilian agricultural cooperatives. The results demonstrate the significance of collective CPA for accessing financing from the Brazilian Development Bank (BNDES) and contributing to collective action theory by offering a political perspective. Moreover, the study enriches CPA literature by identifying two innovative collective CPA tactics: affiliation with central cooperatives and the Organization of Brazilian Cooperatives (OCB). Lastly, the study highlights the importance of cooperation for individual and collective outcomes in practical settings.
Dynamic Analysis and Optimization of Vehicle-Bridge Interaction System under Road Roughness and Time Variability of Element Interpolation Function
Authors: Mo Shuai , Chen Keren , Huang Zurui , Zhang Wei
Published: January 2024

Vehicle-induced load, as one of the main excitation factors to bridge vibration and fatigue damage, plays a vital role in the analyzing of the vehicle-bridge interaction (VBI) system, but is still limited in both spatial location and numerical value. This paper presents an improved VBI system to investigate bridge vibration and vehicle vibration considering the coherent roughness and multiple lanes excitation. The vehicle and bridge subsystems and coherent roughness road are developed and are further integrated to form the VBI system based on the displacement relationship between wheels and the bridge. Further, the solution method of the VBI system is given, and the calculation platform is constructed. Meanwhile, the natural frequencies and mode shapes, as well as the mid-span displacement of the bridge, are verified with the results calculated in commercial software. Subsequently, the responses of the VBI system are investigated under different degrees of freedom of vehicle vibration, bridge damping ratio, road roughness class, multiple lanes, and velocity. It can be concluded that road roughness and velocity have a complex nonlinear relationship with the vibration of the VBI system. Finally, the Pareto strategy is applied to find the optimized value of suspension stiffness and damping, and the depth, unit mass, and elastic modulus of the bridge to minimize the system vibration. The results show an obvious improvement in the vibration of the VBI system.
Novel Oxygenation and Saturation Indices for Mortality Prediction in COVID-19 ARDS Patients: The Impact of Driving Pressure and Mechanical Power
Authors: Aşar Sinan , Rahim Fatih , Rahimi Payam , Acicbe Özlem , Tontu Furkan , Çukurova Zafer
Published: January 2024

Background: The oxygenation index (OI) and oxygen saturation index (OSI) are proven mortality predictors in pediatric and adult patients, traditionally using mean airway pressure (Pmean). We introduce novel indices, replacing Pmean with DP (ΔPinsp), MPdyn, and MPtot, assessing their potential for predicting COVID-19 acute respiratory distress syndrome (ARDS) mortality, comparing them to traditional indices. Methods: We studied 361 adult COVID-19 ARDS patients for 7 days, collecting ΔPinsp, MPdyn, and MPtot, OI-ΔPinsp, OI-MPdyn, OI-MPtot, OSI-ΔPinsp, OSI-MPdyn, and OSI-MPtot. We compared these in surviving and non-surviving patients over the first 7 intensive care unit (ICU) days using Mann–Whitney U test. Logistic regression receiver operating characteristic (ROC) analysis assessed AUC and CI values for ICU mortality on day three. We determined cut-off values using Youden's method and conducted multivariate Cox regression on parameter limits. Results: All indices showed significant differences between surviving and non-surviving patients on the third day of ICU care. The AUC values of OI-ΔPinsp were significantly higher than those of P/F and OI-Pmean ( P values .0002 and <.0001, respectively). Similarly, AUC and CI values of OSI-ΔPinsp and OSI-MPdyn were significantly higher than those of SpO2/FiO2 and OSI-Pmean values (OSI-ΔPinsp: P < .0001, OSI-MPdyn: P values .047 and .028, respectively). OI-ΔPinsp, OSI-ΔPinsp, OI-MPdyn, OSI-MPdyn, OI-MPtot, and OSI-MPtot had AUC values of 0.72, 0.71, 0.69, 0.68, 0.66, and 0.64, respectively, with cut-off values associated with hazard ratios and P values of 7.06 (HR = 1.84, P = .002), 8.04 (HR = 2.00, P ≤ .0001), 7.12 (HR = 1.68, P = .001), 5.76 (HR = 1.70, P ≤ .0001), 10.43 (HR = 1.52, P = .006), and 10.68 (HR = 1.66, P = .001), respectively. Conclusions: Critical values of all indices were associated to higher ICU mortality rates and extended mechanical ventilation durations. The OI-ΔPinsp, OSI-ΔPinsp, and OSI-MPdyn indices displayed the strongest predictive capabilities for ICU mortality. These novel indices offer valuable insights for intensivists in the clinical management and decision-making process for ARDS patients.