bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Figure S1 from Tumor Volume Growth Rates and Doubling Times during Active Surveillance of IDH-mutant Low-Grade Glioma
Authors: Bhatia Ankush , Moreno Raquel , Reiner Anne S. , Nandakumar Subhiksha , Walch Henry S. , Thomas Teena M. , Nicklin Philip J. , Choi Ye , Skakodub Anna , Malani Rachna , Prabhakaran Vivek , Tiwari Pallavi , Diaz Maria , Panageas Katherine S. , Mellinghoff Ingo K. , Bale Tejus A. , Young Robert J.
Published: January 2024

Supplementary Figure S1. Somatic genomic alterations in the cohort of IDH-mutant gliomas.
Supplementary Table S4 from Intraoperative Integrated Diagnostic System for Malignant Central Nervous System Tumors
Authors: Hayashi Takahiro , Tateishi Kensuke , Matsuyama Shinichiro , Iwashita Hiromichi , Miyake Yohei , Oshima Akito , Honma Hirokuni , Sasame Jo , Takabayashi Katsuhiro , Sugino Kyoka , Hirata Emi , Udaka Naoko , Matsushita Yuko , Kato Ikuma , Hayashi Hiroaki , Nakamura Taishi , Ikegaya Naoki , Takayama Yutaro , Sonoda Masaki , Oka Chihiro , Sato Mitsuru , Isoda Masataka , Kato Miyui , Uchiyama Kaho , Tanaka Tamon , Muramatsu Toshiki , Miyake Shigeta , Suzuki Ryosuke , Takadera Mutsumi , Tatezuki Junya , Ayabe Junichi , Suenaga Jun , Matsunaga Shigeo , Miyahara Kosuke , Manaka Hiroshi , Murata Hidetoshi , Yokoyama Takaakira , Tanaka Yoshihide , Shuto Takashi , Ichimura Koichi , Kato Shingo , Yamanaka Shoji , Cahill Daniel P. , Fujii Satoshi , Shankar Ganesh M. , Yamamoto Tetsuya
Published: January 2024

Summary of intraoperative integrated diagnosis (i-ID) and permanent integrated diagnosis (p-ID) for prospective cohort (101 cases)
Supplementary Table S5 from PET/CT Biomarkers Enable Risk Stratification of Patients with Relapsed/Refractory Diffuse Large B-cell Lymphoma Enrolled in the LOTIS-2 Clinical Trial
Authors: Alderuccio Juan Pablo , Reis Isildinha M. , Hamadani Mehdi , Nachiappan Muthiah , Leslom Salman , Kahl Brad S. , Ai Weiyun Z. , Radford John , Solh Melhem , Ardeshna Kirit M. , Hess Brian T. , Lunning Matthew A. , Zinzani Pier Luigi , Stathis Anastasios , Carlo-Stella Carmelo , Lossos Izidore S. , Caimi Paolo F. , Han Sunwoo , Yang Fei , Kuker Russ A. , Moskowitz Craig H.
Published: January 2024

Duration of complete metabolic response in months by baseline PET/CT metric low and high categories (N=33).
Supplementary Table S4 from PET/CT Biomarkers Enable Risk Stratification of Patients with Relapsed/Refractory Diffuse Large B-cell Lymphoma Enrolled in the LOTIS-2 Clinical Trial
Authors: Alderuccio Juan Pablo , Reis Isildinha M. , Hamadani Mehdi , Nachiappan Muthiah , Leslom Salman , Kahl Brad S. , Ai Weiyun Z. , Radford John , Solh Melhem , Ardeshna Kirit M. , Hess Brian T. , Lunning Matthew A. , Zinzani Pier Luigi , Stathis Anastasios , Carlo-Stella Carmelo , Lossos Izidore S. , Caimi Paolo F. , Han Sunwoo , Yang Fei , Kuker Russ A. , Moskowitz Craig H.
Published: January 2024

Baseline PET/CT metrics by chemotherapy treatment response.
Supplementary Fig. S6 from Intraoperative Integrated Diagnostic System for Malignant Central Nervous System Tumors
Authors: Hayashi Takahiro , Tateishi Kensuke , Matsuyama Shinichiro , Iwashita Hiromichi , Miyake Yohei , Oshima Akito , Honma Hirokuni , Sasame Jo , Takabayashi Katsuhiro , Sugino Kyoka , Hirata Emi , Udaka Naoko , Matsushita Yuko , Kato Ikuma , Hayashi Hiroaki , Nakamura Taishi , Ikegaya Naoki , Takayama Yutaro , Sonoda Masaki , Oka Chihiro , Sato Mitsuru , Isoda Masataka , Kato Miyui , Uchiyama Kaho , Tanaka Tamon , Muramatsu Toshiki , Miyake Shigeta , Suzuki Ryosuke , Takadera Mutsumi , Tatezuki Junya , Ayabe Junichi , Suenaga Jun , Matsunaga Shigeo , Miyahara Kosuke , Manaka Hiroshi , Murata Hidetoshi , Yokoyama Takaakira , Tanaka Yoshihide , Shuto Takashi , Ichimura Koichi , Kato Shingo , Yamanaka Shoji , Cahill Daniel P. , Fujii Satoshi , Shankar Ganesh M. , Yamamoto Tetsuya
Published: January 2024

Genomic characterization of chromosome 1p/19q and TERT promoter status in IDH mutant glioma cases
Supplementary Table S2 from PET/CT Biomarkers Enable Risk Stratification of Patients with Relapsed/Refractory Diffuse Large B-cell Lymphoma Enrolled in the LOTIS-2 Clinical Trial
Authors: Alderuccio Juan Pablo , Reis Isildinha M. , Hamadani Mehdi , Nachiappan Muthiah , Leslom Salman , Kahl Brad S. , Ai Weiyun Z. , Radford John , Solh Melhem , Ardeshna Kirit M. , Hess Brian T. , Lunning Matthew A. , Zinzani Pier Luigi , Stathis Anastasios , Carlo-Stella Carmelo , Lossos Izidore S. , Caimi Paolo F. , Han Sunwoo , Yang Fei , Kuker Russ A. , Moskowitz Craig H.
Published: January 2024

Study representativeness table.
Supplementary Table S1 from PET/CT Biomarkers Enable Risk Stratification of Patients with Relapsed/Refractory Diffuse Large B-cell Lymphoma Enrolled in the LOTIS-2 Clinical Trial
Authors: Alderuccio Juan Pablo , Reis Isildinha M. , Hamadani Mehdi , Nachiappan Muthiah , Leslom Salman , Kahl Brad S. , Ai Weiyun Z. , Radford John , Solh Melhem , Ardeshna Kirit M. , Hess Brian T. , Lunning Matthew A. , Zinzani Pier Luigi , Stathis Anastasios , Carlo-Stella Carmelo , Lossos Izidore S. , Caimi Paolo F. , Han Sunwoo , Yang Fei , Kuker Russ A. , Moskowitz Craig H.
Published: January 2024

Baseline patient characteristics.
Supplementary Fig. S3 from Intraoperative Integrated Diagnostic System for Malignant Central Nervous System Tumors
Authors: Hayashi Takahiro , Tateishi Kensuke , Matsuyama Shinichiro , Iwashita Hiromichi , Miyake Yohei , Oshima Akito , Honma Hirokuni , Sasame Jo , Takabayashi Katsuhiro , Sugino Kyoka , Hirata Emi , Udaka Naoko , Matsushita Yuko , Kato Ikuma , Hayashi Hiroaki , Nakamura Taishi , Ikegaya Naoki , Takayama Yutaro , Sonoda Masaki , Oka Chihiro , Sato Mitsuru , Isoda Masataka , Kato Miyui , Uchiyama Kaho , Tanaka Tamon , Muramatsu Toshiki , Miyake Shigeta , Suzuki Ryosuke , Takadera Mutsumi , Tatezuki Junya , Ayabe Junichi , Suenaga Jun , Matsunaga Shigeo , Miyahara Kosuke , Manaka Hiroshi , Murata Hidetoshi , Yokoyama Takaakira , Tanaka Yoshihide , Shuto Takashi , Ichimura Koichi , Kato Shingo , Yamanaka Shoji , Cahill Daniel P. , Fujii Satoshi , Shankar Ganesh M. , Yamamoto Tetsuya
Published: January 2024

Illustrative cases in the retrospective cohort
Supplementary Fig. S1 from Intraoperative Integrated Diagnostic System for Malignant Central Nervous System Tumors
Authors: Hayashi Takahiro , Tateishi Kensuke , Matsuyama Shinichiro , Iwashita Hiromichi , Miyake Yohei , Oshima Akito , Honma Hirokuni , Sasame Jo , Takabayashi Katsuhiro , Sugino Kyoka , Hirata Emi , Udaka Naoko , Matsushita Yuko , Kato Ikuma , Hayashi Hiroaki , Nakamura Taishi , Ikegaya Naoki , Takayama Yutaro , Sonoda Masaki , Oka Chihiro , Sato Mitsuru , Isoda Masataka , Kato Miyui , Uchiyama Kaho , Tanaka Tamon , Muramatsu Toshiki , Miyake Shigeta , Suzuki Ryosuke , Takadera Mutsumi , Tatezuki Junya , Ayabe Junichi , Suenaga Jun , Matsunaga Shigeo , Miyahara Kosuke , Manaka Hiroshi , Murata Hidetoshi , Yokoyama Takaakira , Tanaka Yoshihide , Shuto Takashi , Ichimura Koichi , Kato Shingo , Yamanaka Shoji , Cahill Daniel P. , Fujii Satoshi , Shankar Ganesh M. , Yamamoto Tetsuya
Published: January 2024

Single nucleotide detection threshold
Figure S4 from Tumor-Infiltrating CD103+ Tissue-Resident Memory T Cells and CD103−CD8+ T Cells in HNSCC Are Linked to Outcome in Primary but not Metastatic Disease
Authors: von Witzleben Adrian , Ellis Matthew , Thomas Gareth J. , Hoffmann Thomas K. , Jackson Richard , Laban Simon , Ottensmeier Christian H.
Published: January 2024

suppl. Figure S4
Supplementary Table S8 from Phase I Dose-Escalation Study of the Safety and Pharmacokinetics of AGS15E Monotherapy in Patients with Metastatic Urothelial Carcinoma
Authors: Petrylak Daniel P. , Eigl Bernhard J. , George Saby , Heath Elisabeth I. , Hotte Sebastien J. , Chism David D. , Nabell Lisle M. , Picus Joel , Cheng Susanna Y. , Appleman Leonard J. , Sonpavde Guru P. , Morgans Alicia K. , Pourhosseini Pourya , Wu Ruishan , Standley Laura , Croitoru Ruslan , Yu Evan Y.
Published: January 2024

Supplementary Table S8. Serum PK Parameters of MMAE at Cycle 1, Day 15, PK Analysis Set
Supplementary Table S7 from Phase I Dose-Escalation Study of the Safety and Pharmacokinetics of AGS15E Monotherapy in Patients with Metastatic Urothelial Carcinoma
Authors: Petrylak Daniel P. , Eigl Bernhard J. , George Saby , Heath Elisabeth I. , Hotte Sebastien J. , Chism David D. , Nabell Lisle M. , Picus Joel , Cheng Susanna Y. , Appleman Leonard J. , Sonpavde Guru P. , Morgans Alicia K. , Pourhosseini Pourya , Wu Ruishan , Standley Laura , Croitoru Ruslan , Yu Evan Y.
Published: January 2024

Supplementary Table S7. Serum PK Parameters of MMAE at Cycle 1, Day 1, PK Analysis Set
Supplementary Table S5 from Phase I Dose-Escalation Study of the Safety and Pharmacokinetics of AGS15E Monotherapy in Patients with Metastatic Urothelial Carcinoma
Authors: Petrylak Daniel P. , Eigl Bernhard J. , George Saby , Heath Elisabeth I. , Hotte Sebastien J. , Chism David D. , Nabell Lisle M. , Picus Joel , Cheng Susanna Y. , Appleman Leonard J. , Sonpavde Guru P. , Morgans Alicia K. , Pourhosseini Pourya , Wu Ruishan , Standley Laura , Croitoru Ruslan , Yu Evan Y.
Published: January 2024

Supplementary Table S5. Serum PK Parameters of AGS15E ADC at Cycle 1, Day 1 by Dose Group, PK Analysis Set
Supplementary Table S3 from Phase I Dose-Escalation Study of the Safety and Pharmacokinetics of AGS15E Monotherapy in Patients with Metastatic Urothelial Carcinoma
Authors: Petrylak Daniel P. , Eigl Bernhard J. , George Saby , Heath Elisabeth I. , Hotte Sebastien J. , Chism David D. , Nabell Lisle M. , Picus Joel , Cheng Susanna Y. , Appleman Leonard J. , Sonpavde Guru P. , Morgans Alicia K. , Pourhosseini Pourya , Wu Ruishan , Standley Laura , Croitoru Ruslan , Yu Evan Y.
Published: January 2024

Supplementary Table S3. SLITRK6 Expression Levels, H-Score: Parts A, B, and C,
Expansion Phase (FAS)
Supplementary Table S14 from Phase I Dose-Escalation Study of the Safety and Pharmacokinetics of AGS15E Monotherapy in Patients with Metastatic Urothelial Carcinoma
Authors: Petrylak Daniel P. , Eigl Bernhard J. , George Saby , Heath Elisabeth I. , Hotte Sebastien J. , Chism David D. , Nabell Lisle M. , Picus Joel , Cheng Susanna Y. , Appleman Leonard J. , Sonpavde Guru P. , Morgans Alicia K. , Pourhosseini Pourya , Wu Ruishan , Standley Laura , Croitoru Ruslan , Yu Evan Y.
Published: January 2024

Supplementary Table S14. BOR, ORR, and DCR With Confirmation; Part A, Escalation Phase
Supplementary Table S13 from Phase I Dose-Escalation Study of the Safety and Pharmacokinetics of AGS15E Monotherapy in Patients with Metastatic Urothelial Carcinoma
Authors: Petrylak Daniel P. , Eigl Bernhard J. , George Saby , Heath Elisabeth I. , Hotte Sebastien J. , Chism David D. , Nabell Lisle M. , Picus Joel , Cheng Susanna Y. , Appleman Leonard J. , Sonpavde Guru P. , Morgans Alicia K. , Pourhosseini Pourya , Wu Ruishan , Standley Laura , Croitoru Ruslan , Yu Evan Y.
Published: January 2024

Supplementary Table S13. Statistical Assessment of Dose Proportionality for TAb, Power Model, PK Analysis Set
Supplementary Table S10 from Phase I Dose-Escalation Study of the Safety and Pharmacokinetics of AGS15E Monotherapy in Patients with Metastatic Urothelial Carcinoma
Authors: Petrylak Daniel P. , Eigl Bernhard J. , George Saby , Heath Elisabeth I. , Hotte Sebastien J. , Chism David D. , Nabell Lisle M. , Picus Joel , Cheng Susanna Y. , Appleman Leonard J. , Sonpavde Guru P. , Morgans Alicia K. , Pourhosseini Pourya , Wu Ruishan , Standley Laura , Croitoru Ruslan , Yu Evan Y.
Published: January 2024

Supplementary Table S10. Serum PK Parameters of Tab at Cycle 1, Day 15, PK Analysis Set
Supplementary Figure S1 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

Patient flow diagram
Supplementary Table S2 from FDA Approval Summary: Alpelisib for PIK3CA-Related Overgrowth Spectrum
Authors: Singh Sonia , Bradford Diana , Li Xiaoxue , Mishra-Kalyani Pallavi S. , Shen Yuan-Li , Wang Lingshan , Zhao Hong , Xiong Ye , Liu Jiang , Charlab Rosane , Kraft Jeffrey , Khasar Sachia , Miller Claudia P. , Rivera Donna R. , Kluetz Paul G. , Pazdur Richard , Beaver Julia A. , Singh Harpreet , Donoghue Martha
Published: January 2024

Laboratory Abnormalities Worsening from Baseline in ≥10% of Patients in EPIK-P1
Supplementary Fig. 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

TME of melanoma NR represents a potential target for therapy.
Data 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

AbstractPurpose:
To assess the impact of PHF6 alterations on clinical outcome and therapeutical actionability in T-cell acute lymphoblastic leukemia (T-ALL).
Experimental Design:
We described PHF6 alterations in an adult cohort of T-ALL from the French trial Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-2003/2005 and retrospectively analyzed clinical outcomes between PHF6-altered (PHF6ALT) and wild-type patients. We also used EPIC and chromatin immunoprecipitation sequencing data of patient samples to analyze the epigenetic landscape of PHF6ALT T-ALLs. We consecutively evaluated 5-azacitidine efficacy, alone or combined with venetoclax, in PHF6ALT T-ALL.
Results:
We show that PHF6 alterations account for 47% of cases in our cohort and demonstrate that PHF6ALT T-ALL presented significantly better clinical outcomes. Integrative analysis of DNA methylation and histone marks shows that PHF6ALT are characterized by DNA hypermethylation and H3K27me3 loss at promoters physiologically bivalent in thymocytes. Using patient-derived xenografts, we show that PHF6ALT T-ALL respond to the 5-azacytidine alone. Finally, synergism with the BCL2-inhibitor venetoclax was demonstrated in refractory/relapsing (R/R) PHF6ALT T-ALL using fresh samples. Importantly, we report three cases of R/R PHF6ALT patients who were successfully treated with this combination.
Conclusions:
Overall, our study supports the use of PHF6 alterations as a biomarker of sensitivity to 5-azacytidine and venetoclax combination in R/R T-ALL.
Data from Overall Survival and Exploratory Biomarker Analyses of Abemaciclib plus Trastuzumab with or without Fulvestrant versus Trastuzumab plus Chemotherapy in HR+, HER2+ Metastatic Breast Cancer Patients
Authors: Tolaney Sara M. , Goel Shom , Nadal Jorge , Denys Hannelore , Borrego Manuel R. , Litchfield Lacey M. , Liu Jiangang , Appiah Adams K. , Chen Yanyun , André Fabrice
Published: January 2024

AbstractPurpose:
The monarcHER trial has shown that abemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, combined with fulvestrant and trastuzumab, improves progression-free survival (PFS) in hormone receptor–positive (HR+), HER2-positive (HER2+) advanced breast cancer (ABC) compared with standard-of-care (SOC) chemotherapy combined with trastuzumab. We report the final overall survival (OS) analysis, updated safety and efficacy data, and exploratory biomarker results from monarcHER.
Patients and Methods:
monarcHER (NCT02675231), a randomized, multicenter, open-label, phase II trial, enrolled 237 patients across Arm A (abemaciclib, trastuzumab, fulvestrant), Arm B (abemaciclib, trastuzumab), and Arm C (SOC chemotherapy, trastuzumab). Following the statistical plan, OS and PFS were estimated in all arms. RNA sequencing (RNA-seq) was performed on archival tissue.
Results:
Median OS was 31.1 months in Arm A, 29.2 months in Arm B, and 20.7 months in Arm C [A vs. C: HR, 0.71; 95% confidence interval (CI), 0.48–1.05; nominal two-sided P value 0.086; B vs. C: HR 0.83 (95% CI, 0.57–1.23); nominal two-sided P value 0.365]. Updated PFS and safety findings were consistent with previous results. The most frequently reported treatment-emergent adverse events included diarrhea, fatigue, nausea, neutrophil count decrease, and anemia. In exploratory RNA-seq analyses, Luminal subtypes were associated with longer PFS [8.6 vs. 5.4 months (HR, 0.54; 95% CI, 0.38–0.79)] and OS [31.7 vs. 19.7 months (HR, 0.68; 95% CI, 0.46–1.00)] compared with non-Luminal.
Conclusions:
In this phase II trial, abemaciclib + trastuzumab ± fulvestrant numerically improved median OS in women with HR+, HER2+ ABC compared with SOC chemotherapy + trastuzumab.
Data from Tumor-Infiltrating CD103+ Tissue-Resident Memory T Cells and CD103−CD8+ T Cells in HNSCC Are Linked to Outcome in Primary but not Metastatic Disease
Authors: von Witzleben Adrian , Ellis Matthew , Thomas Gareth J. , Hoffmann Thomas K. , Jackson Richard , Laban Simon , Ottensmeier Christian H.
Published: January 2024

AbstractPurpose:
High numbers of tumor-infiltrating lymphocytes (TIL) are linked to better survival in patients with cancer. Tissue-resident memory T cells (TRM; CD8+CD103+) are recognized as a key player of anticancer immune response. To assess TRM cells in primary, metastatic, and recurrent head and neck squamous cell carcinoma (HNSCC), we developed a tissue microarray (TMA) and used multiplex IHC (MxIHC).
Experimental Design:
Samples from primary tumors of 379 HNSCC cases treated at Southampton Hospitals between 2000 and 2016 were collected and analyzed. Of these, 105 cases had lymph node metastases and 82 recurrences. A TMA was generated with triplicate cores for each sample. MxIHC with a stain-and-strip approach was performed using CD8, CD103, and TIM3. Scanned slides were analyzed (digital image analysis) and quality checked (QC).
Results:
After QC, 194 primary tumors, 76 lymph node metastases, and 65 recurrences were evaluable. Alcohol consumption was statistically significantly correlated with a reduction of TRM cells in primary tumors (nondrinker vs. heavy drinker: P = 0.0036). The known survival benefit of TRM cell infiltration in primary tumors was not found for lymph node metastasis. In recurrences, a high TRM cell number led to a favorable outcome after 12 months. The checkpoint molecule TIM3, was expressed significantly higher on TRM and non-TRM cells in the lymph node compared with primary tumors (P < 0.0001), which was also seen in recurrences (P = 0.0134 and P = 0.0007, respectively).
Conclusions:
We confirm the prognostic impact of TIL in primary tumors and in recurrences. TRM cell density in lymph node metastases was not linked to outcome. The role of TIM3, as a therapeutic target remains to be defined.
Data from FDA Approval Summary: Alpelisib for PIK3CA-Related Overgrowth Spectrum
Authors: Singh Sonia , Bradford Diana , Li Xiaoxue , Mishra-Kalyani Pallavi S. , Shen Yuan-Li , Wang Lingshan , Zhao Hong , Xiong Ye , Liu Jiang , Charlab Rosane , Kraft Jeffrey , Khasar Sachia , Miller Claudia P. , Rivera Donna R. , Kluetz Paul G. , Pazdur Richard , Beaver Julia A. , Singh Harpreet , Donoghue Martha
Published: January 2024

Abstract
On April 5, 2022, FDA granted accelerated approval to alpelisib for the treatment of adult and pediatric patients 2 years of age and older with severe manifestations of PIK3CA-related overgrowth spectrum (PROS) who require systemic therapy. Efficacy was evaluated using real-world data (RWD) from EPIK-P1 (NCT04285723), a single-arm clinical study in patients 2 years of age and older with severe or life-threatening PROS who received alpelisib as part of an expanded access program (EAP) for compassionate use. The primary endpoint was confirmed radiologic response rate at week 24 as determined by blinded independent central review (BICR), using volumetric-based criteria given the atypical growth pattern and irregular shape of PROS lesions. Radiologic response was defined as a ≥20% reduction from baseline in the sum of measurable target lesion volume in up to three lesions. Of the 37 patients in the efficacy population, 27% [95% confidence interval (CI), 14–44] had a radiologic response at week 24. Duration of response (DOR) was an additional efficacy outcome measure, and among responders, 60% had a response lasting ≥12 months. Furthermore, supportive clinical documentation suggested early signals of clinical benefit (i.e., improvement in PROS-related signs and symptoms). The most common (≥10%) adverse reactions were diarrhea, stomatitis, and hyperglycemia.
Data from A Phase II Trial of the CD40 Agonist Sotigalimab (APX005M) in Combination with Nivolumab in Subjects with Metastatic Melanoma with Disease Progression on Anti-PD-1
Authors: Weiss Sarah A. , Sznol Mario , Shaheen Montaser , Berciano-Guerrero Miguel-Angel , Muñoz-Couselo Eva , Rodríguez-Abreu Delvys , Boni Valentina , Schuchter Lynn M. , Gonzalez Cao Maria , Arance Fernandez Ana , Wei Wei , Ganti Apar Kishor , Hauke Ralph J. , Berrocal Alfonso , Iannotti Nicholas O. , Hsu Frank J. , Kluger Harriet M.
Published: January 2024

Abstract
Purpose: Disease progression during or after anti-PD-1-based treatment is common in advanced melanoma. Sotigalimab is a CD40 agonist antibody with unique epitope specificity and Fc-receptor binding profile optimized for activation of CD40-expressing antigen presenting cells. Preclinical data indicated that CD40 agonists combined with anti-PD1 could overcome resistance to anti-PD-1. Methods: We conducted a multi-center, open-label, phase II trial to evaluate the combination of sotigalimab 0.3mg/kg and nivolumab 360mg q3wk in patients with advanced melanoma following confirmed disease progression on anti-PD-1. The primary objective was to determine the objective response rate (ORR). Results: Thirty-eight subjects were enrolled and evaluable for safety. Thirty-three were evaluable for activity. Five confirmed partial responses (PR) were observed for an ORR of 15%. Two PRs are ongoing at 45.9+ and 26+ months while the other 3 responders relapsed at 41.1, 18.7, and 18.4 months. Median duration of response was at least 26 months. Two additional patients had stable disease for > 6 months. Thirty-four patients (89%) experienced at least one adverse event (AE) and 13% experienced a grade 3 AE related to sotigalimab. The most common AEs were pyrexia, chills, nausea, fatigue, pruritus, elevated liver function, rash, vomiting, headache, arthralgia, asthenia, myalgia, and diarrhea. There were no treatment-related SAEs, deaths, or discontinuation of sotigalimab due to AEs. Conclusions: Sotigalimab plus nivolumab had a favorable safety profile consistent with the toxicity profiles of each agent. The combination resulted in durable and prolonged responses in a subset of patients with anti-PD-1-resistant melanoma, warranting further evaluation in this setting.
Data 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

AbstractPurpose:
Disease progression during or after anti-PD-1-based treatment is common in advanced melanoma. Sotigalimab is a CD40 agonist antibody with a unique epitope specificity and Fc receptor binding profile optimized for activation of CD40-expressing antigen-presenting cells. Preclinical data indicated that CD40 agonists combined with anti-PD1 could overcome resistance to anti-PD-1.
Patients and Methods:
We conducted a multicenter, open-label, phase II trial to evaluate the combination of sotigalimab 0.3 mg/kg and nivolumab 360 mg every 3 weeks in patients with advanced melanoma following confirmed disease progression on a PD-1 inhibitor. The primary objective was to determine the objective response rate (ORR).
Results:
Thirty-eight subjects were enrolled and evaluable for safety. Thirty-three were evaluable for activity. Five confirmed partial responses (PR) were observed for an ORR of 15%. Two PRs are ongoing at 45.9+ and 26+ months, whereas the other three responders relapsed at 41.1, 18.7, and 18.4 months. The median duration of response was at least 26 months. Two additional patients had stable disease for >6 months. Thirty-four patients (89%) experienced at least one adverse event (AE), and 13% experienced a grade 3 AE related to sotigalimab. The most common AEs were pyrexia, chills, nausea, fatigue, pruritus, elevated liver function, rash, vomiting, headache, arthralgia, asthenia, myalgia, and diarrhea. There were no treatment-related SAEs, deaths, or discontinuation of sotigalimab due to AEs.
Conclusions:
Sotigalimab plus nivolumab had a favorable safety profile consistent with the toxicity profiles of each agent. The combination resulted in durable and prolonged responses in a subset of patients with anti-PD-1-resistant melanoma, warranting further evaluation in this setting.

See related commentary by Wu and Luke, p. 9
Data 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

AbstractPurpose:
A single arm, phase II trial of carboplatin, nab-paclitaxel, and pembrolizumab (CNP) in metastatic triple-negative breast cancer (mTNBC) was designed to evaluate overall response rate (ORR), progression-free survival (PFS), duration of response (DOR), safety/tolerability, overall survival (OS), and identify pathologic and transcriptomic correlates of response to therapy.
Patients and Methods:
Patients with ≤2 prior therapies for metastatic disease were treated with CNP regardless of tumor programmed cell death-ligand 1 status. Core tissue biopsies were obtained prior to treatment initiation. ORR was assessed using a binomial distribution. Survival was analyzed via the Kaplan–Meier method. Bulk RNA sequencing was employed for correlative studies.
Results:
Thirty patients were enrolled. The ORR was 48.0%: 2 (7%) complete responses (CR), 11 (41%) partial responses (PR), and 8 (30%) stable disease (SD). The median DOR for patients with CR or PR was 6.4 months [95% confidence interval (CI), 4–8.5 months]. For patients with CR, DOR was >24 months. Overall median PFS and OS were 5.8 (95% CI, 4.7–8.5 months) and 13.4 months (8.9–17.3 months), respectively. We identified unique transcriptomic landscapes associated with each RECIST category of radiographic treatment response. In CR and durable PR, IGHG1 expression was enriched. IGHG1high tumors were associated with improved OS (P = 0.045) and were concurrently enriched with B cells and follicular helper T cells, indicating IGHG1 as a promising marker for lymphocytic infiltration and robust response to chemo-immunotherapy.
Conclusions:
Pretreatment tissue sampling in mTNBC treated with CNP reveals transcriptomic signatures that may predict radiographic responses to chemo-immunotherapy.
Prevalence of Clarithromycin-Resistant Helicobacter pylori Strains in Zambia: A Sub-Saharan African Country
Authors: Kebotsamang Tshegofatso , Munkombwe Derick , Bwalya Lalusha , Kelly Paul , Kayamba Violet
Published: January 2024

Introduction: Helicobacter pylori (H. pylori) is one of the most important infections globally, affecting more than 50% of the human population. Clarithromycin (CLA)-containing regimens are recommended for empirical eradication of H. pylori in populations with less than 15% resistance. The aim of this study was to estimate the prevalence of CLA resistance in samples collected from Zambian patients to determine if CLA is suitable for first-line H. pylori empirical treatment. Methodology: We used archival biopsy samples collected from dyspeptic patients undergoing endoscopy. The samples had been snap-frozen immediately after collection and stored at −80°C. We performed multiplex real-time PCR using Bosphore Helicobacter pylori Genotyping Kits v1, Istanbul, Turkey, to determine the presence of wild-type H. pylori and three mutations, A2142G, A2142C, and A2143G, of domain V in 23s rRNA gene. Results: We tested 259 gastric biopsy samples from patients with dyspepsia, of which 136 (53%) were from females. The median age was 48 years (IQR 40–61 years). Endoscopically, most of the patients, 164 (63%), had a normal gastric mucosa. CLA resistance was found in 48 (28%) samples, with A2142G mutation in 23 (13%), A2143G mutation in 32 (18%), and double mutations A2142C and A2143G in 6 (3%). Conclusions: The presence of significant levels of CLA resistance in Zambia suggests that it should not be used as first-line empirical treatment for H. pylori infection. However, with a limitation of suitable alternatives, there is an urgent need to formulate new treatment approaches.
Low-Dose Versus Standard-Dose Alteplase in Bridging Therapy for Large Vessel Stroke: A Systematic Review and Meta-Analysis
Authors: Yang Ta-Wei , Lee Ya-Han , Lo Wei-Cheng , Chen I-Ting , Lin Han-Chun , Chen Ming-Hua , Lee Chiao-Hua , Hsu Yuan-Pin , Tam Ka-Wai
Published: January 2024

INTRODUCTION The efficacy and safety of low- and standard-dose alteplase for acute ischemic stroke (AIS) have not been consistently compared in previous studies. Nevertheless, the distinctions in the effects of low- and standard-dose alteplase, particularly within the context of bridging therapy (BT) for large vessel occlusion (LVO), warrant further exploration. This study compared clinical outcomes between BT with low- and standard-dose alteplase in patients with LVO-related AIS.
METHODS We performed a search for randomized controlled trials and prospective or retrospective cohort studies investigating the clinical outcomes of BT in AIS in the PubMed, Embase, and Cochrane Library databases from inception to November 2022. The outcomes of interest were 90-day functional independence, successful recanalization, symptomatic intracerebral hemorrhage (sICH) and mortality; these outcomes were compared between patients who received BT with low- (primarily 0.6 mg/kg) and standard-dose alteplase (0.9 mg/kg). We used the standard-dose group as the reference and calculated the odds ratio (OR) and its 95% confidence interval (CI) from the raw numbers. Meta-analysis and ethnicity-based subgroup analysis (Asian and non-Asian) were performed.
RESULTS Five observational studies, published after 2017 and including 408 patients, were included. The meta-analysis results demonstrated that compared with BT with standard-dose alteplase, BT with low-dose alteplase did not improve 90-day functional independence (odds ratio, [OR] 1.02; 95% confidence interval [CI], 0.58–1.80). Nevertheless, BT with low-dose alteplase was associated with a comparable successful recanalization rate (OR, 1.35; 95% CI, 0.68–2.67) and similar sICH incidence (OR 0.36; 95% CI, 0.10–1.36), and mortality (OR, 0.64; 95% CI, 0.27–1.54) compared with BT with standard-dose alteplase; however, the above three results were nonsignificant. In the ethnicity-based subgroup analyses, no differences were noted between Asian and non-Asian participants.
CONCLUSIONS In patients with LVO-related AIS, BT with low- or standard-dose alteplase may provide similar efficacy, with no significant differences in sICH incidence and mortality. Additional well-designed prospective studies are required to confirm this result.
Stage I Breast Cancer in the Modern Era: A Retrospective Cohort Study of 328 Patients Diagnosed from 2002 to 2006 with a 14-Year Median Follow-Up
Authors: Hadar Maayan , Friger Michael , Ariad Samuel , Koretz Michael , Delgado Bertha , Tokar Margarita , Bayme Michael , Agassi Ravit , Rosenthal Maia , Dyomin Victor , Belochitski Olga , Amir Noa , Libson Shai , Meirovitz Amichay , Lazarev Irena , Abu-Ghanem Sara , Geffen David B.
Published: January 2024

Introduction: This study aimed to evaluate the long-term outcomes of stage I breast cancer (BC) patients diagnosed during the current era of screening mammography, immunohistochemistry receptor testing, and systemic adjuvant therapy. Methods: A retrospective cohort study was conducted on 328 stage I BC patients treated consecutively in a single referral center with a follow-up period of at least 12 years. The primary endpoints were invasive disease-free survival (IDFS) and overall survival (OS). The influence of tumor size, grade, and subtype on the outcomes was analyzed. Results: Most patients were treated by lumpectomy, sentinel node biopsy, and adjuvant endocrine therapy, and most (82%) were of subtype luminal A. Adjuvant chemotherapy was administered to 25.6% of our cohort. Only 24 patients underwent gene expression testing, which was introduced toward the end of the study period. Mean IDFS was 14.64 years, with a 15-year IDFS of 75.6%. Mean OS was 15.28 years with a 15-year OS of 74.9%. In a Cox multivariate analysis, no clinical or pathologic variable impacted on OS and only tumor size (<1 cm vs. 1–2 cm) impacted significantly on IDFS. During follow-up, 20.1% of the cohort developed second primary cancers, including BC. The median time to diagnosis of a second BC was 6.49 years. Conclusion: The study results emphasize the importance of long-term follow-up and screening for subsequent malignancies of patients with stage I BC and support the need for using prognostic and predictive indicators beyond the routine clinicopathological characteristics in luminal A patients.
Análise das críticas à herdabilidade sob a perspectiva de Larry Laudan
Authors: Guerreiro Carlos Antônio Rodrigues , Antonelli-Ponti Mayra , Versuti Fabiana Maris
Published: January 2024

Este artigo discute o conceito de herdabilidade, empregado pela genética do comportamento, genética molecular e a teoria da herdabilidade, sob a perspectiva do modelo reticulado de racionalidade científica, de Larry Laudan. Analisa os argumentos contrários à utilização do termo herdabilidade focando principalmente nos resultados de experimentos da genética do comportamento. Conclui que algumas críticas ao termo herdabilidade são válidas tais como o termo poder ser confuso para o público em geral, mas podem ser extremas como as que propõem sua extinção. A análise desenvolvida leva à conclusão de que a herdabilidade, tanto pela genética do comportamento, quanto pela genética molecular, é útil para seus respectivos fins.  Os autores consideram que ao invés de ser extinto, o termo pode ser utilizado considerando mais análises, resultados e conclusões, sendo, portanto, essa a escolha mais racional e progressiva.
Napoli è mille colori. La città brulicante: da Il paese di Cuccagna di Matilde Serao alla narrativa di Maurizio de Giovanni
Authors: Palma Loredana
Published: January 2024

Tra le città maggiormente “attraversate” dalla letteratura di Otto e Novecento un posto rilevante è occupato da Napoli. Descritta dai suoi figli e da viaggiatori di passaggio, in romanzi e reportage, immortalata in raffigurazioni di vario genere - dalle vedute di Pitloo alle tele di Migliaro, dalla fotografia alla cinematografia (da Mario Martone de Il sindaco del rione Sanità, all’ultimo Sorrentino di È stata la mano di Dio, passando per due “stranieri” come Turturro e Ozpetek, registi rispettivamente di Passione e di Napoli velata), Napoli viene descritta in mille modi diversi, mai però in maniera asettica. Nel racconto della città, infatti, non mancano mai due elementi essenziali: lo sguardo di chi osserva e l’elemento umano, che costituisce parte integrante del paesaggio. Evocata persino in musica (da Marechiare fino a Napul’è di Pino Daniele), la città resta comunque un mistero ineffabile per i suoi stessi abitanti e la sua visione si rifrange in mille immagini, dal bianco e nero al colore, ognuna delle quali contiene un pezzo di verità. Alla contemplazione estatica, dall’alto, del Golfo e del Vesuvio, si contrappongono, nel basso, tanto nella scrittura quanto nelle raffigurazioni visive, vicoli bui, strade brulicanti di vita, amori e dolori, speranza e rassegnazione, lusso e miseria. Sarà quest’ultimo il percorso che ci condurrà, dall’Ottocento al Duemila, dalla città brulicante del Paese di Cuccagna di Matilde Serao a quella altrettanto tumultuosa di Maurizio de Giovanni, senza che Napoli abbia perso la sua capacità di stupire e di essere raccontata nei suoi mille colori diversi.
Neurobiological Causal Models of Language Processing
Authors: Fitz Hartmut , Hagoort Peter , Petersson Karl Magnus
Published: January 2024

The language faculty is physically realized in the neurobiological infrastructure of the human brain. Despite significant efforts, an integrated understanding of this system remains a formidable challenge. What is missing from most theoretical accounts is a specification of the neural mechanisms that implement language function. Computational models that have been put forward generally lack an explicit neurobiological foundation. We propose a neurobiologically informed causal modeling approach which offers a framework for how to bridge this gap. A neurobiological causal model is a mechanistic description of language processing that is grounded in, and constrained by, the characteristics of the neurobiological substrate. It intends to model the generators of language behavior at the level of implementational causality. We describe key features and neurobiological component parts from which causal models can be built and provide guidelines on how to implement them in model simulations. Then we outline how this approach can shed new light on the core computational machinery for language, the long-term storage of words in the mental lexicon and combinatorial processing in sentence comprehension. In contrast to cognitive theories of behavior, causal models are formulated in the “machine language” of neurobiology which is universal to human cognition. We argue that neurobiological causal modeling should be pursued in addition to existing approaches. Eventually, this approach will allow us to develop an explicit computational neurobiology of language.
Consultations on the System of Indigenous and Afromexican Communal Security and the Right to be Consulted in Mexico
Authors: Stachurski Alexander
Published: January 2024

The right to be consulted is a legal institution that originated in 1989 in the United Nations Convention 169, requiring states to conduct a consultation process of Indigenous peoples and communities on issues potentially impacting them. The Mexican state has subsequently implemented the right to be consulted in its legal system. The consultation processes were often riddled with inconsistencies and the violation of the rights of Indigenous communities and peoples. In this paper I analysed the case study of the consultation process in Guerrero, by researching press articles, engaging in participant observation and conducting interviews. I looked for similarities between the Guerrero consultations and past consultations in Juchitán, Sonora, and Campeche. I identified several violations and manipulations consistent with the history of the right to be consulted. In the last part of the article, I compared the proposed acts and established their potential impact on security in Guerrero.
The Role of Precipitation and Salinity Effect in Multidecadal Changes and Long-Term Trend of the Indonesian Throughflow
Authors: Lu Xi , Hu Shijian , Sprintall Janet
Published: January 2024

Multidecadal variability of the Indonesian Throughflow (ITF) is crucial for the Indo-Pacific and global climate due to significant interbasin exchanges of heat and freshwater. Previous studies suggest that both wind and buoyancy forcing may drive ITF variability, but the role of precipitation and salinity effect in the variability of ITF on multidecadal time scales remains largely unexplored. Here, we investigate the multidecadal changes and long-term trend of the ITF transport during the past six decades, with a focus on the role of precipitation and salinity effect. The diverse datasets consistently indicate a substantial upward trend in the halosteric component of geostrophic transport of ITF in the outflow region at 114°E during the six decades. We find that the meridional differences of the salinity trend in the outflow region explain the increasing trend of the halosteric component of ITF transport. On a larger scale, the tropical western Pacific Ocean and Indonesian seas have experienced significant freshening, which has strengthened the Indo-Pacific pressure gradient and thus enhanced the ITF. In contrast, the equatorial trade wind in the western Pacific Ocean has weakened over recent decades, implying that changes in wind forcing have contributed to weakening the ITF. The combined effect of strengthened halosteric and weakened thermosteric components has resulted in a weak strengthening for the total ITF with large uncertainties. Although both the thermosteric and halosteric components are associated with natural climate modes, our results suggest that the importance of salinity effect is likely increasing given the enhanced water cycle under global warming.
Long-Term Variations and Its Driving Factors of the TOA Albedo over the Loess Plateau
Authors: Wang Qianru , Zhang Shuhua
Published: January 2024

Solar radiation balances significantly affect Earth’s surface energy balance and climate change. Studying top-of-the-atmosphere (TOA) albedo changes is of great significance for understanding Earth’s energy budget and atmospheric circulation. The Loess Plateau (LP), located in the middle reaches of the Yellow River in China, is one of the most severely eroded areas in the world. In this paper, long-term remote sensing data were used to analyze the changes in the TOA albedo in the LP from 1982 to 2016. The results showed that the TOA albedo, its atmospheric contribution (AC), and surface contribution (SC) exhibited decreasing trends: −0.0012, −0.0010, and −0.0003 a−1. The spatial pattern of the TOA albedo was similar to AC, which indicates that AC dominates the change in the TOA albedo. We detected driving factors for AC and SC and found that the cloud fraction (CF) was the main driving factor of the AC, whereas the soil moisture (SM) dominated the SC. The driving factors of two typical regions with a significantly decreasing trend in the TOA albedo were also detected. The Mu Us Desert, where vegetation improved significantly, showed a decreasing trend in the TOA albedo, and we found that NDVI was the main driving factor for the change in the SC of the TOA albedo. However, the Eastern Qilian Mountains, where snow cover decreased in recent years, also showed a significant decreasing trend in the TOA albedo; the SC here was mainly driven by the changes in snow cover days (SCD). These results indicate that changes in the surface environment alter the radiation balance.

Significance Statement

The Loess Plateau in China is one of the most severe cases of soil erosion in the world, and ecological restoration projects have been carried out to recover the fragile ecological environment. Our study was designed to explore changes in the top-of-the-atmosphere (TOA) albedo of the Loess Plateau between 1982 and 2016 using a long time series of multisource satellite products, and driving factors in the atmosphere and at the surface were analyzed. We concluded that the TOA albedo of the Loess Plateau decreased over 35 years, and its atmospheric contribution dominated the change in the TOA albedo. However, the significant ecological improvement in the Loess Plateau, especially in the central vegetation recovery region, such as the Mu Us Desert, was also strongly related to the regional changes in the surface contribution of the TOA albedo. The climate changes had a considerable impact on the eastern branch of the Qilian Mountains in the Qinghai region, where the decline in snow cover days affected the local Alpine meadow ecosystems; therefore, snow cover days also played a decisive role in the local variation of the surface contribution of the TOA albedo.
Synergistic Retrievals of Ice in High Clouds from Elastic Backscatter Lidar, Ku-Band Radar, and Submillimeter Wave Radiometer Observations
Authors: Grecu Mircea , Yorks John E.
Published: January 2024

In this study, we investigate the synergy of elastic backscatter lidar, Ku-band radar, and submillimeter-wave radiometer measurements in the retrieval of ice from satellite observations. The synergy is analyzed through the generation of a large dataset of ice water content (IWC) profiles and simulated lidar, radar and radiometer observations. The characteristics of the instruments (frequencies, sensitivities, etc.) are set based on the expected characteristics of instruments of the Atmosphere Observing System (AOS) mission. A hold-out validation methodology is used to assess the accuracy of the IWC profiles retrieved from various combinations of observations from the three instruments. Specifically, the IWC and associated observations are randomly divided into two datasets, one for training and the other for evaluation. The training dataset is used to train the retrieval algorithm, while the evaluation dataset is used to assess the retrieval performance. The dataset of IWC profiles is derived from CloudSat reflectivity and CALIOP lidar observations. The retrieval of the ice water content IWC profiles from the computed observations is achieved in two steps. In the first step, a class, of 18 potential classes characterized by different vertical distribution of IWC, is estimated from the observations. The 18 classes are predetermined based on the k-means clustering algorithm. In the second step, the IWC profile is estimated using an ensemble Kalman smoother algorithm that uses the estimated class as a priori information. The results of the study show that the synergy of lidar, radar, and radiometer observations is significant in the retrieval of the IWC profiles. Nevertheless, it should be mentioned that this synergy was found under idealized conditions, and additional work might be required to materialize it in practice. The inclusion of the lidar backscatter observations in the retrieval process has a larger impact on the retrieval performance than the inclusion of the radar observations. As ice clouds have a significant impact on atmospheric radiative processes, this work is relevant to ongoing efforts to reduce uncertainties in climate analyses and projections.