bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Advanced Age in Humans and Mouse Models of Glioblastoma Show Decreased Survival from Extratumoral Influence
Authors: Johnson Margaret , Bell April , Lauing Kristen L. , Ladomersky Erik , Zhai Lijie , Penco-Campillo Manon , Shah Yajas , Mauer Elizabeth , Xiu Joanne , Nicolaides Theodore , Drumm Michael , McCortney Kathleen , Elemento Olivier , Kim Miri , Bommi Prashant , Low Justin T. , Memon Ruba , Wu Jennifer , Zhao Junfei , Mi Xinlei , Glantz Michael J. , Sengupta Soma , Castro Brandyn , Yamini Bakhtiar , Horbinski Craig , Baker Darren J. , Walunas Theresa L. , Schiltz Gary E. , Lukas Rimas V. , Wainwright Derek A.
Published: December 2023

AbstractPurpose:
Glioblastoma (GBM) is the most common aggressive primary malignant brain tumor in adults with a median age of onset of 68 to 70 years old. Although advanced age is often associated with poorer GBM patient survival, the predominant source(s) of maladaptive aging effects remains to be established. Here, we studied intratumoral and extratumoral relationships between adult patients with GBM and mice with brain tumors across the lifespan.
Experimental Design:
Electronic health records at Northwestern Medicine and the NCI SEER databases were evaluated for GBM patient age and overall survival. The commercial Tempus and Caris databases, as well as The Cancer Genome Atlas were profiled for gene expression, DNA methylation, and mutational changes with varying GBM patient age. In addition, gene expression analysis was performed on the extratumoral brain of younger and older adult mice with or without a brain tumor. The survival of young and old wild-type or transgenic (INK-ATTAC) mice with a brain tumor was evaluated after treatment with or without senolytics and/or immunotherapy.
Results:
Human patients with GBM ≥65 years of age had a significantly decreased survival compared with their younger counterparts. While the intra-GBM molecular profiles were similar between younger and older patients with GBM, non-tumor brain tissue had a significantly different gene expression profile between young and old mice with a brain tumor and the eradication of senescent cells improved immunotherapy-dependent survival of old but not young mice.
Conclusions:
This work suggests a potential benefit for combining senolytics with immunotherapy in older patients with GBM.
Data from Near-Infrared Spectral Tomography for Predicting Residual Cancer Burden during Early-Stage Neoadjuvant Chemotherapy for Breast Cancer
Authors: Cao Xu , Muller Kristen E. , Chamberlin Mary D. , Gui Jiang , Kaufman Peter A. , Schwartz Gary N. , diFlorio-Alexander Roberta M. , Pogue Brian W. , Paulsen Keith D. , Jiang Shudong
Published: December 2023

AbstractPurpose:
The aim of this study is to investigate whether near-infrared spectral tomography (NIRST) might serve as a reliable prognostic tool to predict residual cancer burden (RCB) in patients with breast cancer undergoing neoadjuvant chemotherapy (NAC) based upon early treatment response measurements.
Experimental Design:
A total of thirty-five patients with breast cancer receiving NAC were included in this study. NIRST imaging was performed at multiple time points, including: before treatment, at end of the first cycle, at the mid-point, and post-NAC treatments. From reconstructed NIRST images, average values of total hemoglobin (HbT) were obtained for both the tumor region and contralateral breast at each time point. RCB scores/classes were assessed by a pathologist using histologic slides of the surgical specimen obtained after completing NAC. Logistic regression of the normalized early percentage change of HbT in the tumor region (ΔHbT%) was used to predict RCB and determine its significance as an indicator for differentiating cases within each RCB class.
Results:
The ΔHbT% at the end of the first cycle, as compared with pretreatment levels, showed excellent prognostic capability in differentiating RCB-0 from RCB-I/II/III or RCB-II from RCB-0/I/III (P < 0.001). Corresponding area under the curve (AUC) values for these comparisons were 0.97 and 0.94, and accuracy values were 0.90 and 0.83, respectively.
Conclusions:
NIRST holds promise as a potential clinical tool that can be seamlessly integrated into existing clinical workflow within the infusion suite. By providing early assessment of RCB, NIRST has potential to improve breast cancer patient management strategies.
Data from Circulating Tumor DNA Analysis in Advanced Urothelial Carcinoma: Insights from Biological Analysis and Extended Clinical Follow-up
Authors: Lindskrog Sia V. , Birkenkamp-Demtröder Karin , Nordentoft Iver , Laliotis George , Lamy Philippe , Christensen Emil , Renner Derrick , Andreasen Tine G. , Lange Naja , Sharma Shruti , ElNaggar Adam C. , Liu Minetta C. , Sethi Himanshu , Aleshin Alexey , Agerbæk Mads , Jensen Jørgen B. , Dyrskjøt Lars
Published: December 2023

AbstractPurpose:
To investigate whether circulating tumor DNA (ctDNA) assessment in patients with muscle-invasive bladder cancer predicts treatment response and provides early detection of metastatic disease.
Experimental Design:
We present full follow-up results (median follow-up: 68 months) from a previously described cohort of 68 neoadjuvant chemotherapy (NAC)-treated patients who underwent longitudinal ctDNA testing (712 plasma samples). In addition, we performed ctDNA evaluation of 153 plasma samples collected before and after radical cystectomy (RC) in a separate cohort of 102 NAC-naïve patients (median follow-up: 72 months). Total RNA sequencing of tumors was performed to investigate biological characteristics of ctDNA shedding tumors.
Results:
Assessment of ctDNA after RC identified metastatic relapse with a sensitivity of 94% and specificity of 98% using the expanded follow-up data for the NAC-treated patients. ctDNA dynamics during NAC was independently associated with patient outcomes when adjusted for pathologic downstaging (HR = 4.7; P = 0.029). For the NAC-naïve patients, ctDNA was a prognostic predictor before (HR = 3.4; P = 0.0005) and after RC (HR = 17.8; P = 0.0002). No statistically significant difference in recurrence-free survival for patients without detectable ctDNA at diagnosis was observed between the cohorts. Baseline ctDNA positivity was associated with the Basal/Squamous (Ba/Sq) subtype and enrichment of epithelial-to-mesenchymal transition and cell cycle–associated gene sets.
Conclusions:
ctDNA is prognostic in NAC-treated and NAC-naïve patients with more than 5 years follow-up and outperforms pathologic downstaging in predicting treatment efficacy. Patients without detectable ctDNA at diagnosis may benefit significantly less from NAC, but additional studies are needed.
Data from Olaparib and Ceralasertib (AZD6738) in Patients with Triple-Negative Advanced Breast Cancer: Results from Cohort E of the plasmaMATCH Trial (CRUK/15/010)
Authors: Ring Alistair , Kilburn Lucy S. , Pearson Alex , Moretti Laura , Afshari-Mehr Angelica , Wardley Andrew M. , Gurel Bora , Macpherson Iain R. , Riisnaes Ruth , Baird Richard D. , Martin Sue , Roylance Rebecca , Johnson Hannah , Ferreira Ana , Winter Matthew C. , Dunne Kathryn , Copson Ellen , Hickish Tamas , Burcombe Russell , Randle Kat , Serra Violeta , Llop-Guevara Alba , Bliss Judith M. , Turner Nicolas C.
Published: December 2023

AbstractPurpose:
Approximately 10% to 15% of triple-negative breast cancers (TNBC) have deleterious mutations in BRCA1 and BRCA2 and may benefit from PARP inhibitor treatment. PARP inhibitors may also increase exogenous replication stress and thereby increase sensitivity to inhibitors of ataxia telangiectasia and Rad3-related (ATR) protein. This phase II study examined the activity of the combination of PARP inhibitor, olaparib, and ATR inhibitor, ceralasertib (AZD6738), in patients with advanced TNBC.
Patients and Methods:
Patients with TNBC on most recent biopsy who had received 1 or 2 lines of chemotherapy for advanced disease or had relapsed within 12 months of (neo)adjuvant chemotherapy were eligible. Treatment was olaparib 300 mg twice a day continuously and celarasertib 160 mg on days 1–7 on a 28-day cycle until disease progression. The primary endpoint was confirmed objective response rate (ORR). Tissue and plasma biomarker analyses were preplanned to identify predictors of response.
Results:
70 evaluable patients were enrolled. Germline BRCA1/2 mutations were present in 10 (14%) patients and 3 (4%) patients had somatic BRCA mutations. The confirmed ORR was 12/70; 17.1% (95% confidence interval, 10.4–25.5). Responses were observed in patients without germline or somatic BRCA1/2 mutations, including patients with mutations in other homologous recombination repair genes and tumors with functional homologous recombination deficiency by RAD51 foci.
Conclusions:
The response rate to olaparib and ceralasertib did not meet prespecified criteria for activity in the overall evaluable population, but responses were observed in patients who would not be expected to respond to olaparib monotherapy.
Data from Tumor-Infiltrating Normal B Cells Revealed by Immunoglobulin Repertoire Clonotype Analysis Are Highly Prognostic and Crucial for Antitumor Immune Responses in DLBCL
Authors: Xu-Monette Zijun Y. , Li Yong , Snyder Thomas , Yu Tiantian , Lu Tingxun , Tzankov Alexandar , Visco Carlo , Bhagat Govind , Qian Wenbin , Dybkaer Karen , Chiu April , Tam Wayne , Zu Youli , Hsi Eric D. , Hagemeister Fredrick B. , Wang Yingjun , Go Heounjeong , Ponzoni Maurilio , Ferreri Andrés J.M. , Møller Michael B. , Parsons Benjamin M. , Fan Xiangshan , van Krieken J. Han , Piris Miguel A. , Winter Jane N. , Au Qingyan , Kirsch Ilan , Zhang Mingzhi , Shaughnessy John , Xu Bing , Young Ken H.
Published: December 2023

AbstractPurpose:
Tumor-infiltrating B lymphocytes (TIL-B) have demonstrated prognostic and predictive significance in solid cancers. In this study, we aimed to distinguish TIL-Bs from malignant B-cells in diffuse large B-cell lymphoma (DLBCL) and determine the clinical and biological significance.
Experimental Design:
A total of 269 patients with de novo DLBCL from the International DLBCL R-CHOP Consortium Program were studied. Ultra-deep sequencing of the immunoglobulin genes was performed to determine B-cell clonotypes. The frequencies and numbers of TIL-B clonotypes in individual repertoires were correlated with patient survival, gene expression profiling (GEP) data, and frequencies of DLBCL-infiltrating immune cells quantified by fluorescent multiplex IHC at single-cell resolution.
Results:
TIL-B abundance, evaluated by frequencies of normal B-cell clonotypes in the immunoglobulin repertoires, remarkably showed positive associations with significantly better survival of patients in our sequenced cohorts. DLBCLs with high versus low TIL-B abundance displayed distinct GEP signatures, increased pre-memory B-cell state and naïve CD4 T-cell state fractions, and higher CD4+ T-cell infiltration. TIL-B frequency, as a new biomarker in DLBCL, outperformed the germinal center (GC) B-cell–like/activated B-cell–like classification and TIL-T frequency. The identified TIL-B–high GEP signature, including genes upregulated during T-dependent B-cell activation and those highly expressed in normal GC B cells and T cells, showed significant favorable prognostic effects in several external validation cohorts.
Conclusions:
TIL-B frequency is a significant prognostic factor in DLBCL and plays a crucial role in antitumor immune responses. This study provides novel insights into the prognostic determinants in DLBCL and TIL-B functions with important therapeutic implications.
Data from Potential of Fecal Microbiota Transplantation to Prevent Acute GVHD: Analysis from a Phase II Trial
Authors: Rashidi Armin , Ebadi Maryam , Rehman Tauseef Ur , Elhusseini Heba , Kazadi David , Halaweish Hossam , Khan Mohammad H. , Hoeschen Andrea , Cao Qing , Luo Xianghua , Kabage Amanda J. , Lopez Sharon , Holtan Shernan G. , Weisdorf Daniel J. , Khoruts Alexander , Staley Christopher
Published: December 2023

AbstractPurpose:
Intestinal microbiota disruptions early after allogeneic hematopoietic cell transplantation have been associated with increased risk for acute GVHD (aGVHD). In our recent randomized phase II trial of oral, encapsulated, third-party fecal microbiota transplantation (FMT) versus placebo, FMT at the time of neutrophil recovery was safe and ameliorated dysbiosis. Here, we evaluated in post hoc analysis whether donor microbiota engraftment after FMT may protect against aGVHD.
Experimental Design:
We analyzed pre- and post-FMT stool samples and estimated donor microbiota engraftment (a preplanned secondary endpoint) by determining the fraction of post-FMT microbiota formed by unique donor taxa (donor microbiota fraction; dMf).
Results:
dMf was higher in patients who later developed grade I or no aGVHD (median 33.9%; range, 1.6%–74.3%) than those who developed grade II–IV aGVHD (median 25.3%; range, 2.2%–34.8%; P = 0.006). The cumulative incidence of grade II–IV aGVHD by day 180 was lower in the group with greater-than-median dMf than the group with less-than-median dMf [14.3% (95% confidence interval, CI, 2.1–37.5) vs. 76.9% (95% CI, 39.7–92.8), P = 0.008]. The only determinant of dMf in cross-validated least absolute shrinkage and selection operator (LASSO)-regularized regression was the patient's pre-FMT microbiota diversity (Pearson correlation coefficient −0.82, P = 1.6 × 10−9), indicating more potent microbiota modulation by FMT in patients with more severe dysbiosis. Microbiota network analysis revealed major rewiring including changes in the most central nodes, without emergence of keystone species, as a potential mechanism of FMT effect.
Conclusions:
FMT may have protective effects against aGVHD, especially in patients with more severe microbiota disruptions.
Supplementary Table S3 from Development of a Novel CLDN18.2-directed Monoclonal Antibody and Antibody–Drug Conjugate for Treatment of CLDN18.2-Positive Cancers
Authors: O'Brien Neil A. , McDermott Martina S.J. , Zhang Jun , Gong Ke Wei , Lu Ming , Hoffstrom Benjamin , Luo Tong , Ayala Raul , Chau Kevin , Liang Min , Madrid Athena M. , Donahue Timothy R. , Glaspy John A. , Presta Leonard , Slamon Dennis J.
Published: December 2023

Maximum % cytotoxicity and phagocytosis and EC50 values for CLDN18.2-307-mAb in HUPT4 cels
Supplementary Table S1 from Development of a Novel CLDN18.2-directed Monoclonal Antibody and Antibody–Drug Conjugate for Treatment of CLDN18.2-Positive Cancers
Authors: O'Brien Neil A. , McDermott Martina S.J. , Zhang Jun , Gong Ke Wei , Lu Ming , Hoffstrom Benjamin , Luo Tong , Ayala Raul , Chau Kevin , Liang Min , Madrid Athena M. , Donahue Timothy R. , Glaspy John A. , Presta Leonard , Slamon Dennis J.
Published: December 2023

Binding of CLDN18.2 mAbs to cell lines that either naturally express or are engineered to express CLDN18 isoforms
Supplementary Table S1 from Anticancer Efficacy of KRASG12C Inhibitors Is Potentiated by PAK4 Inhibitor KPT9274 in Preclinical Models of KRASG12C-Mutant Pancreatic and Lung Cancers
Authors: Khan Husain Yar , Nagasaka Misako , Aboukameel Amro , Alkhalili Osama , Uddin Md. Hafiz , Bannoura Sahar F. , Mzannar Yousef , Azar Ibrahim , Beal Eliza W. , Tobon Miguel E. , Kim Steve H. , Beydoun Rafic , Baloglu Erkan , Senapedis William , El-Rayes Bassel F. , Philip Philip A. , Mohammad Ramzi M. , Shields Anthony F. , Al Hallak Mohammed Najeeb , Azmi Asfar S.
Published: December 2023

Suppl Table S1 shows the sequences of primers used for RT-qPCR
Supplementary Fig S7 from Anticancer Efficacy of KRASG12C Inhibitors Is Potentiated by PAK4 Inhibitor KPT9274 in Preclinical Models of KRASG12C-Mutant Pancreatic and Lung Cancers
Authors: Khan Husain Yar , Nagasaka Misako , Aboukameel Amro , Alkhalili Osama , Uddin Md. Hafiz , Bannoura Sahar F. , Mzannar Yousef , Azar Ibrahim , Beal Eliza W. , Tobon Miguel E. , Kim Steve H. , Beydoun Rafic , Baloglu Erkan , Senapedis William , El-Rayes Bassel F. , Philip Philip A. , Mohammad Ramzi M. , Shields Anthony F. , Al Hallak Mohammed Najeeb , Azmi Asfar S.
Published: December 2023

Suppl Fig S7 shows the quantification of spheroid disintegration assay data shown in Figure 3C
Supplementary Fig S5 from Anticancer Efficacy of KRASG12C Inhibitors Is Potentiated by PAK4 Inhibitor KPT9274 in Preclinical Models of KRASG12C-Mutant Pancreatic and Lung Cancers
Authors: Khan Husain Yar , Nagasaka Misako , Aboukameel Amro , Alkhalili Osama , Uddin Md. Hafiz , Bannoura Sahar F. , Mzannar Yousef , Azar Ibrahim , Beal Eliza W. , Tobon Miguel E. , Kim Steve H. , Beydoun Rafic , Baloglu Erkan , Senapedis William , El-Rayes Bassel F. , Philip Philip A. , Mohammad Ramzi M. , Shields Anthony F. , Al Hallak Mohammed Najeeb , Azmi Asfar S.
Published: December 2023

Suppl Fig S5 shows effects of KPT9274 and MRTX849 combinations on the proliferation of KRAS4BG12C and KRAS4BG12D MEFs
Supplementary Fig S4 from Anticancer Efficacy of KRASG12C Inhibitors Is Potentiated by PAK4 Inhibitor KPT9274 in Preclinical Models of KRASG12C-Mutant Pancreatic and Lung Cancers
Authors: Khan Husain Yar , Nagasaka Misako , Aboukameel Amro , Alkhalili Osama , Uddin Md. Hafiz , Bannoura Sahar F. , Mzannar Yousef , Azar Ibrahim , Beal Eliza W. , Tobon Miguel E. , Kim Steve H. , Beydoun Rafic , Baloglu Erkan , Senapedis William , El-Rayes Bassel F. , Philip Philip A. , Mohammad Ramzi M. , Shields Anthony F. , Al Hallak Mohammed Najeeb , Azmi Asfar S.
Published: December 2023

Suppl Fig S4 shows effects of KPT9274 and KRAS G12Ci combinations on the proliferation of HPAC and MIA-AMG-R cells
Supplementary Fig S1 from Anticancer Efficacy of KRASG12C Inhibitors Is Potentiated by PAK4 Inhibitor KPT9274 in Preclinical Models of KRASG12C-Mutant Pancreatic and Lung Cancers
Authors: Khan Husain Yar , Nagasaka Misako , Aboukameel Amro , Alkhalili Osama , Uddin Md. Hafiz , Bannoura Sahar F. , Mzannar Yousef , Azar Ibrahim , Beal Eliza W. , Tobon Miguel E. , Kim Steve H. , Beydoun Rafic , Baloglu Erkan , Senapedis William , El-Rayes Bassel F. , Philip Philip A. , Mohammad Ramzi M. , Shields Anthony F. , Al Hallak Mohammed Najeeb , Azmi Asfar S.
Published: December 2023

Suppl Fig S1 shows chemical structure of KPT9274
Supplementary Figure 5 from Radiotherapy-induced Immune Response Enhanced by Selective HDAC6 Inhibition
Authors: Noonepalle Satish Kumar R. , Grindrod Scott , Aghdam Nima , Li Xintang , Gracia-Hernandez Maria , Zevallos-Delgado Christian , Jung Mira , Villagra Alejandro , Dritschilo Anatoly
Published: December 2023

Supplementary Figure 5
Supplementary Figure 1 from Radiotherapy-induced Immune Response Enhanced by Selective HDAC6 Inhibition
Authors: Noonepalle Satish Kumar R. , Grindrod Scott , Aghdam Nima , Li Xintang , Gracia-Hernandez Maria , Zevallos-Delgado Christian , Jung Mira , Villagra Alejandro , Dritschilo Anatoly
Published: December 2023

Supplementary Figure 1
Table S6 from Novel Thienoduocarmycin–Trastuzumab ADC Demonstrates Strong Antitumor Efficacy with Favorable Safety Profile in Preclinical Studies
Authors: Valsasina Barbara , Orsini Paolo , Caruso Michele , Albanese Clara , Ciavolella Antonella , Cucchi Ulisse , Fraietta Ivan , Melillo Nicola , Fiorentini Francesco , Rizzi Simona , Salsa Matteo , Isacchi Antonella , Gasparri Fabio
Published: December 2023

NMS-P945 trastuzumab ADC PK data
Supplementary Data Figure Legend from Radiotherapy-induced Immune Response Enhanced by Selective HDAC6 Inhibition
Authors: Noonepalle Satish Kumar R. , Grindrod Scott , Aghdam Nima , Li Xintang , Gracia-Hernandez Maria , Zevallos-Delgado Christian , Jung Mira , Villagra Alejandro , Dritschilo Anatoly
Published: December 2023

Supplementary Data Figure Legend
Table S5 from Novel Thienoduocarmycin–Trastuzumab ADC Demonstrates Strong Antitumor Efficacy with Favorable Safety Profile in Preclinical Studies
Authors: Valsasina Barbara , Orsini Paolo , Caruso Michele , Albanese Clara , Ciavolella Antonella , Cucchi Ulisse , Fraietta Ivan , Melillo Nicola , Fiorentini Francesco , Rizzi Simona , Salsa Matteo , Isacchi Antonella , Gasparri Fabio
Published: December 2023

NMS-P945 stability in plasma
Figure S3 from Novel Thienoduocarmycin–Trastuzumab ADC Demonstrates Strong Antitumor Efficacy with Favorable Safety Profile in Preclinical Studies
Authors: Valsasina Barbara , Orsini Paolo , Caruso Michele , Albanese Clara , Ciavolella Antonella , Cucchi Ulisse , Fraietta Ivan , Melillo Nicola , Fiorentini Francesco , Rizzi Simona , Salsa Matteo , Isacchi Antonella , Gasparri Fabio
Published: December 2023

Biochemical characterization of trastuzumab conjugated to MMAE and Deruxtecan
Figure S1 from Novel Thienoduocarmycin–Trastuzumab ADC Demonstrates Strong Antitumor Efficacy with Favorable Safety Profile in Preclinical Studies
Authors: Valsasina Barbara , Orsini Paolo , Caruso Michele , Albanese Clara , Ciavolella Antonella , Cucchi Ulisse , Fraietta Ivan , Melillo Nicola , Fiorentini Francesco , Rizzi Simona , Salsa Matteo , Isacchi Antonella , Gasparri Fabio
Published: December 2023

Cathepsin cleavage of NMS-P945 derivatized with cysteine
Supplementary Table S6 from C-X-C Motif Chemokine Ligand 9 Correlates with Favorable Prognosis in Triple-Negative Breast Cancer by Promoting Immune Cell Infiltration
Authors: Cao Xi , Song Yu , Wu Huanwen , Ren Xinyu , Sun Qiang , Liang Zhiyong
Published: December 2023

Supplementary Table S6 shows the expression level of other CXCL members between the low- and high-CXCL9 mRNA groups in basal-like subtype of TCGA BRCA cohort (n=140).
Supplementary Table S5 from C-X-C Motif Chemokine Ligand 9 Correlates with Favorable Prognosis in Triple-Negative Breast Cancer by Promoting Immune Cell Infiltration
Authors: Cao Xi , Song Yu , Wu Huanwen , Ren Xinyu , Sun Qiang , Liang Zhiyong
Published: December 2023

Supplementary Table S5 shows the expression level of 9 immune checkpoints between the low- and high-CXCL9 mRNA groups in basal-like subtype of TCGA BRCA cohort (n=140).
Supplementary Table S3 from C-X-C Motif Chemokine Ligand 9 Correlates with Favorable Prognosis in Triple-Negative Breast Cancer by Promoting Immune Cell Infiltration
Authors: Cao Xi , Song Yu , Wu Huanwen , Ren Xinyu , Sun Qiang , Liang Zhiyong
Published: December 2023

Supplementary Table S3 shows the uni-variate and multi-variate overall survival analysis for patients in the basal-like subtype of TCGA BRCA cohort (n=138).
Supplementary Figure S1 from C-X-C Motif Chemokine Ligand 9 Correlates with Favorable Prognosis in Triple-Negative Breast Cancer by Promoting Immune Cell Infiltration
Authors: Cao Xi , Song Yu , Wu Huanwen , Ren Xinyu , Sun Qiang , Liang Zhiyong
Published: December 2023

Supplementary Figure S1 shows the quantitative analysis of percent positivity of CXCL9 expression on ICs (A) and TCs (B) across 268 TNBC patients in the PUMCH cohort. The Scatter plot indicates distribution, and blue horizontal bar indicates median.
Supplementary Figure 3 from Microtubule-Targeting Combined with HDAC Inhibition Is a Novel Therapeutic Strategy for Diffuse Intrinsic Pontine Gliomas
Authors: Ehteda Anahid , Khan Aaminah , Rajakumar Gayathiri , Vanniasinghe Anne S. , Gopalakrishnan Anjana , Liu Jie , Tsoli Maria , Ziegler David S.
Published: December 2023

Drug concentrations of TRX-E-009-1.
Supplementary Figure 2 from Microtubule-Targeting Combined with HDAC Inhibition Is a Novel Therapeutic Strategy for Diffuse Intrinsic Pontine Gliomas
Authors: Ehteda Anahid , Khan Aaminah , Rajakumar Gayathiri , Vanniasinghe Anne S. , Gopalakrishnan Anjana , Liu Jie , Tsoli Maria , Ziegler David S.
Published: December 2023

Microtubule disruption.
Supplementary Figure 1 from Microtubule-Targeting Combined with HDAC Inhibition Is a Novel Therapeutic Strategy for Diffuse Intrinsic Pontine Gliomas
Authors: Ehteda Anahid , Khan Aaminah , Rajakumar Gayathiri , Vanniasinghe Anne S. , Gopalakrishnan Anjana , Liu Jie , Tsoli Maria , Ziegler David S.
Published: December 2023

TRX-E-009-1 treatment indicates a change in the cell cycle process in DIPG.
Table S1 from FBXO24 Suppresses Breast Cancer Tumorigenesis by Targeting LSD1 for Ubiquitination
Authors: Dong Bo , Song Xiang , Wang Xinzhao , Dai Tao , Wang Jianlin , Yu Zhiyong , Deng Jiong , Evers B. Mark , Wu Yadi
Published: December 2023

The used antibodies including company, catalog number and dilution.
Supplementary Figure 1 from FBXO24 Suppresses Breast Cancer Tumorigenesis by Targeting LSD1 for Ubiquitination
Authors: Dong Bo , Song Xiang , Wang Xinzhao , Dai Tao , Wang Jianlin , Yu Zhiyong , Deng Jiong , Evers B. Mark , Wu Yadi
Published: December 2023

FBXO24 regulates LSD1 at protein levels.
Supplementary Figure 7 from Competing Engagement of β-arrestin Isoforms Balances IGF1R/p53 Signaling and Controls Melanoma Cell Chemotherapeutic Responsiveness
Authors: Cismas Sonia , Pasca Sylvya , Crudden Caitrin , Trocoli Drakensjo Iara , Suleymanova Naida , Zhang Simin , Gebhard Benjamin , Song Dawei , Neo Shiyong , Shibano Takashi , Smith Terry J. , Calin George A. , Girnita Ada , Girnita Leonard
Published: December 2023

Effect of combination treatment on p53-activation in skin melanoma malignant phenotype in in vitro 3D models
Supplementary Figure 6 from Competing Engagement of β-arrestin Isoforms Balances IGF1R/p53 Signaling and Controls Melanoma Cell Chemotherapeutic Responsiveness
Authors: Cismas Sonia , Pasca Sylvya , Crudden Caitrin , Trocoli Drakensjo Iara , Suleymanova Naida , Zhang Simin , Gebhard Benjamin , Song Dawei , Neo Shiyong , Shibano Takashi , Smith Terry J. , Calin George A. , Girnita Ada , Girnita Leonard
Published: December 2023

Effect of β-arrestin imbalance on response to dacarbazine (DTIC)
Table S3 from m6A-Mediated Biogenesis of circDDIT4 Inhibits Prostate Cancer Progression by Sequestrating ELAVL1/HuR
Authors: Kong Zhe , Lu Yali , Yang Yue , Chang Kun , Lin Yan , Huang Yan , Wang Chenji , Zhang Lu , Xu Wei , Zhao Shimin , Li Yao
Published: December 2023

Primers used in MeRIP-qPCR.
Table S2 from m6A-Mediated Biogenesis of circDDIT4 Inhibits Prostate Cancer Progression by Sequestrating ELAVL1/HuR
Authors: Kong Zhe , Lu Yali , Yang Yue , Chang Kun , Lin Yan , Huang Yan , Wang Chenji , Zhang Lu , Xu Wei , Zhao Shimin , Li Yao
Published: December 2023

Primers used in qPCR.
Table S1 from m6A-Mediated Biogenesis of circDDIT4 Inhibits Prostate Cancer Progression by Sequestrating ELAVL1/HuR
Authors: Kong Zhe , Lu Yali , Yang Yue , Chang Kun , Lin Yan , Huang Yan , Wang Chenji , Zhang Lu , Xu Wei , Zhao Shimin , Li Yao
Published: December 2023

siRNA sequences used in knockdown experiments.
Figure S6 from m6A-Mediated Biogenesis of circDDIT4 Inhibits Prostate Cancer Progression by Sequestrating ELAVL1/HuR
Authors: Kong Zhe , Lu Yali , Yang Yue , Chang Kun , Lin Yan , Huang Yan , Wang Chenji , Zhang Lu , Xu Wei , Zhao Shimin , Li Yao
Published: December 2023

Ring formation of circDDIT4 regulated by m6A modification.
Figure S5 from m6A-Mediated Biogenesis of circDDIT4 Inhibits Prostate Cancer Progression by Sequestrating ELAVL1/HuR
Authors: Kong Zhe , Lu Yali , Yang Yue , Chang Kun , Lin Yan , Huang Yan , Wang Chenji , Zhang Lu , Xu Wei , Zhao Shimin , Li Yao
Published: December 2023

CircDDIT4-ELAVL1-ANO7 regulates the progression of PCa.
Figure S4 from m6A-Mediated Biogenesis of circDDIT4 Inhibits Prostate Cancer Progression by Sequestrating ELAVL1/HuR
Authors: Kong Zhe , Lu Yali , Yang Yue , Chang Kun , Lin Yan , Huang Yan , Wang Chenji , Zhang Lu , Xu Wei , Zhao Shimin , Li Yao
Published: December 2023

ELAVL1 promotes the development of PCa.
Figure S3 from m6A-Mediated Biogenesis of circDDIT4 Inhibits Prostate Cancer Progression by Sequestrating ELAVL1/HuR
Authors: Kong Zhe , Lu Yali , Yang Yue , Chang Kun , Lin Yan , Huang Yan , Wang Chenji , Zhang Lu , Xu Wei , Zhao Shimin , Li Yao
Published: December 2023

CircDDIT4 specifically binds to ELAVL1.
Figure S1 from m6A-Mediated Biogenesis of circDDIT4 Inhibits Prostate Cancer Progression by Sequestrating ELAVL1/HuR
Authors: Kong Zhe , Lu Yali , Yang Yue , Chang Kun , Lin Yan , Huang Yan , Wang Chenji , Zhang Lu , Xu Wei , Zhao Shimin , Li Yao
Published: December 2023

Cellular localization of circDDIT4
Supplementary Figure 1 from Generating a Murine PTEN Null Cell Line to Discover the Key Role of p110β-PAK1 in Castration-Resistant Prostate Cancer Invasion
Authors: Wang Haizhen , Zhou Yu , Chu Chen , Xiao Jialing , Zheng Shanshan , Korpal Manav , Korn Joshua M. , Penaloza Tiffany , Drake Richard R. , Gan Wenjian , Gao Xueliang
Published: December 2023

Related to Figure 1A.
Supplementary Table 3 from Early Immune Changes Support Signet Ring Cell Dormancy in CDH1-Driven Hereditary Diffuse Gastric Carcinogenesis
Authors: Green Benjamin L. , Gamble Lauren A. , Diggs Laurence P. , Nousome Darryl , Patterson Jesse C. , Joughin Brian A. , Gasmi Billel , Lux Stephanie C. , Samaranayake Sarah G. , Miettinen Markku , Quezado Martha , Hernandez Jonathan M. , Yaffe Michael B. , Davis Jeremy L.
Published: December 2023

Genes from GSEA involving parenchymal stomach cells, metabolism, and T cell signaling.
Supplementary Table 2 from Early Immune Changes Support Signet Ring Cell Dormancy in CDH1-Driven Hereditary Diffuse Gastric Carcinogenesis
Authors: Green Benjamin L. , Gamble Lauren A. , Diggs Laurence P. , Nousome Darryl , Patterson Jesse C. , Joughin Brian A. , Gasmi Billel , Lux Stephanie C. , Samaranayake Sarah G. , Miettinen Markku , Quezado Martha , Hernandez Jonathan M. , Yaffe Michael B. , Davis Jeremy L.
Published: December 2023

Generation of second messenger molecules.
Supplementary Figure 8 from Early Immune Changes Support Signet Ring Cell Dormancy in CDH1-Driven Hereditary Diffuse Gastric Carcinogenesis
Authors: Green Benjamin L. , Gamble Lauren A. , Diggs Laurence P. , Nousome Darryl , Patterson Jesse C. , Joughin Brian A. , Gasmi Billel , Lux Stephanie C. , Samaranayake Sarah G. , Miettinen Markku , Quezado Martha , Hernandez Jonathan M. , Yaffe Michael B. , Davis Jeremy L.
Published: December 2023

GSEA plots of Treg and NK cell gene sets in SRC compared with NEP.
Supplementary Figure 6 from Early Immune Changes Support Signet Ring Cell Dormancy in CDH1-Driven Hereditary Diffuse Gastric Carcinogenesis
Authors: Green Benjamin L. , Gamble Lauren A. , Diggs Laurence P. , Nousome Darryl , Patterson Jesse C. , Joughin Brian A. , Gasmi Billel , Lux Stephanie C. , Samaranayake Sarah G. , Miettinen Markku , Quezado Martha , Hernandez Jonathan M. , Yaffe Michael B. , Davis Jeremy L.
Published: December 2023

Representative slides at 20x magnification from every IHC specimen used for quantification.
Table S1 from BACH1 Loss Exerts Antitumor Effects on Mantle Cell Lymphoma Cells via Inducing a Tumor-Intrinsic Innate Immune Response and Cell-Cycle Arrest
Authors: Li Guilan , Feng Min , Zhang Ziting , Liu Jiangyuan , Zhang Han
Published: December 2023

Table S1 shows the sequences of shRNAs.
Figure S6 from BACH1 Loss Exerts Antitumor Effects on Mantle Cell Lymphoma Cells via Inducing a Tumor-Intrinsic Innate Immune Response and Cell-Cycle Arrest
Authors: Li Guilan , Feng Min , Zhang Ziting , Liu Jiangyuan , Zhang Han
Published: December 2023

Figure S6 shows the BACH1-mediated feedback loops in tumor microenvironment of MCL.
Figure S2 from BACH1 Loss Exerts Antitumor Effects on Mantle Cell Lymphoma Cells via Inducing a Tumor-Intrinsic Innate Immune Response and Cell-Cycle Arrest
Authors: Li Guilan , Feng Min , Zhang Ziting , Liu Jiangyuan , Zhang Han
Published: December 2023

Figure S2 shows the overall survival curves of MCL patients using different expression thresholds.
Table S6 from AMPK Associates with Chromatin and Phosphorylates the TAF-1 Subunit of the Transcription Initiation Complex to Regulate Histone Gene Expression in ALL Cells
Authors: Sun Guangyan , Leclerc Guy J. , Chahar Sanjay , Barredo Julio C.
Published: December 2023

Mass spectrometry analysis of putative TAF1 phosphorylated sites identified in HEK293T cells in response to energy/metabolic stress.
Figure S5 from AMPK Associates with Chromatin and Phosphorylates the TAF-1 Subunit of the Transcription Initiation Complex to Regulate Histone Gene Expression in ALL Cells
Authors: Sun Guangyan , Leclerc Guy J. , Chahar Sanjay , Barredo Julio C.
Published: December 2023

TAF1 inhibition leads to cell growth inhibition and
induction of apoptosis in ALL cells.
Figure S4 from AMPK Associates with Chromatin and Phosphorylates the TAF-1 Subunit of the Transcription Initiation Complex to Regulate Histone Gene Expression in ALL Cells
Authors: Sun Guangyan , Leclerc Guy J. , Chahar Sanjay , Barredo Julio C.
Published: December 2023

Phosphorylation of TAF1 at S1353 impairs regulation of histone gene expression.
Figure S1 from AMPK Associates with Chromatin and Phosphorylates the TAF-1 Subunit of the Transcription Initiation Complex to Regulate Histone Gene Expression in ALL Cells
Authors: Sun Guangyan , Leclerc Guy J. , Chahar Sanjay , Barredo Julio C.
Published: December 2023

AMPKalpha2 binds to chromatin and co-localizes with RNA polymerase II (Pol II) on the TSS region of histone genes.
Data from FBXO24 Suppresses Breast Cancer Tumorigenesis by Targeting LSD1 for Ubiquitination
Authors: Dong Bo , Song Xiang , Wang Xinzhao , Dai Tao , Wang Jianlin , Yu Zhiyong , Deng Jiong , Evers B. Mark , Wu Yadi
Published: December 2023

Abstract
Lysine-specific demethylase 1 (LSD1), a critical chromatin modulator, functions as an oncogene by demethylation of H3K4me1/2. The stability of LSD1 is governed by a complex and intricate process involving ubiquitination and deubiquitination. Several deubiquitinases preserve LSD1 protein levels. However, the precise mechanism underlying the degradation of LSD1, which could mitigate its oncogenic function, remains unknown. To gain a better understanding of LSD1 degradation, we conducted an unbiased siRNA screening targeting all the human SCF family E3 ligases. Our screening identified FBXO24 as a genuine E3 ligase that ubiquitinates and degrades LSD1. As a result, FBXO24 inhibits LSD1-induced tumorigenesis and functions as a tumor suppressor in breast cancer cells. Moreover, FBXO24 exhibits an inverse correlation with LSD1 and is associated with a favorable prognosis in breast cancer patient samples. Taken together, our study uncovers the significant role of FBXO24 in impeding breast tumor progression by targeting LSD1 for degradation.
Implications:
Our study provides comprehensive characterization of the significant role of FBXO24 in impeding breast tumor progression by targeting LSD1 for degradation.
Data from Competing engagement of β-arrestin isoforms balances IGF1R/p53 signaling and controls melanoma cell chemotherapeutic responsiveness
Authors: Cismas Sonia , Pasca Sylvya , Crudden Caitrin , Troccoli Drakensjo Iara , Suleymanova Naida , Zhang Simin , Gebhard Benjamin , Song Dawei , Neo Shiyong , Shibano Takashi , Smith Terry J. , Calin George A. , Girnita Ada , Girnita Leonard
Published: December 2023

Abstract
Constraints on the p53 tumour suppressor pathway have long been associated with the progression, therapeutic resistance, and poor prognosis of melanoma, the most aggressive form of skin cancer. Likewise, the insulin-like growth factor type 1 receptor (IGF1R) is recognized as an essential coordinator of transformation, proliferation, survival, and migration of melanoma cells.
Given that β-arrestin (β-arr) system critically governs the anti/pro-tumorigenic p53/IGF1R signaling pathways through their common E3 ubiquitin-protein ligase MDM2, we explore whether unbalancing this system downstream of IGF1R can enhance the response of melanoma cells to chemotherapy.
Altering β-arr expression demonstrated that both β-arr1-silencing and β-arr2-overexpression (-β-arr1/+β-arr2) facilitated nuclear-to-cytosolic MDM2 translocation accompanied by decreased IGF1R expression, while increasing p53 levels, resulting in reduced cell proliferation/survival. Imbalance towards β-arr2 (-β-arr1/+β-arr2) synergizes with the chemotherapeutic agent, dacarbazine, in promoting melanoma cell toxicity. In both 3D spheroid models and in vivo in zebrafish models, this combination strategy, through dual IGF1R downregulation/p53 activation, limits melanoma cell growth, survival and metastatic spread. In clinical settings, analysis of the TCGA-SKCM patient cohort confirms β-arr1-/β-arr2+ imbalance as a metastatic melanoma vulnerability that may enhance therapeutic benefit. Our findings suggest that under steady-state conditions, IGF1R/p53-tumor promotion/suppression status-quo is preserved by β-arr1/2 homeostasis. Biasing this balance towards β-arr2 can limit the pro-tumorigenic IGF1R activities while enhancing p53 activity, thus reducing multiple cancer-sustaining mechanisms. Combined with other therapeutics, this strategy improves patient responses and outcomes to therapies relying on p53 or IGF1R pathways.
Implications: Altogether, β-arrestin system bias downstream IGF1R is an important metastatic melanoma vulnerability that may be conductive for therapeutic benefit.
Data from Interleukin-6 Facilitates Acute Myeloid Leukemia Chemoresistance via Mitofusin 1–Mediated Mitochondrial Fusion
Authors: Hou Diyu , Zheng Xiaoming , Cai Danni , You Ruolan , Liu Jingru , Wang Xiaoting , Liao Xinai , Tan Maoqing , Lin Liyan , Wang Jin , Zhang Shuxia , Huang Huifang
Published: December 2023

Abstract
Acute myeloid leukemia (AML), an aggressive hematopoietic malignancy, exhibits poor prognosis and a high recurrence rate largely because of primary and secondary drug resistance. Elevated serum IL6 levels have been observed in patients with AML and are associated with chemoresistance. Chemoresistant AML cells are highly dependent on oxidative phosphorylation (OXPHOS), and mitochondrial network remodeling is essential for mitochondrial function. However, IL6-mediated regulation of mitochondrial remodeling and its effectiveness as a therapeutic target remain unclear. We aimed to determine the mechanisms through which IL6 facilitates the development of chemoresistance in AML cells. IL6 upregulated mitofusin 1 (MFN1)-mediated mitochondrial fusion, promoted OXPHOS, and induced chemoresistance in AML cells. MFN1 knockdown impaired the effects of IL6 on mitochondrial function and chemoresistance in AML cells. In an MLL::AF9 fusion gene-induced AML mouse model, IL6 reduced chemosensitivity to cytarabine (Ara-C), a commonly used antileukemia drug, accompanied by increased MFN1 expression, mitochondrial fusion, and OXPHOS status. In contrast, anti-IL6 antibodies downregulated MFN1 expression, suppressed mitochondrial fusion and OXPHOS, enhanced the curative effects of Ara-C, and prolonged overall survival. In conclusion, IL6 upregulated MFN1-mediated mitochondrial fusion in AML, which facilitated mitochondrial respiration, in turn, inducing chemoresistance. Thus, targeting IL6 may have therapeutic implications in overcoming IL6-mediated chemoresistance in AML.
Implications:
IL6 treatment induces MFN1-mediated mitochondrial fusion, promotes OXPHOS, and confers chemoresistance in AML cells. Targeting IL6 regulation in mitochondria is a promising therapeutic strategy to enhance the chemosensitivity of AML.
Supplementary Table S5 from A Novel Saliva and Serum miRNA Panel as a Potential Useful Index for Oral Cancer and the Association of miR-21 with Smoking History: a Pilot Study
Authors: Vageli Dimitra P. , Doukas Panagiotis G. , Shah Rema , Boyi Trinithas , Liu Christina , Judson Benjamin L.
Published: December 2023

Supplementary Table S5 shows saliva, serum, and their combined miRNA levels from OSCC patients and healthy individuals (HC), and their fold-changes (OSCC/HC), in total patients, smokers, and non-smokers.
Supplementary Table S3 from A Novel Saliva and Serum miRNA Panel as a Potential Useful Index for Oral Cancer and the Association of miR-21 with Smoking History: a Pilot Study
Authors: Vageli Dimitra P. , Doukas Panagiotis G. , Shah Rema , Boyi Trinithas , Liu Christina , Judson Benjamin L.
Published: December 2023

Supplementary Table S3 shows targets (mature miRNA) detected by qPCR.
Supplementary Table S2 from A Novel Saliva and Serum miRNA Panel as a Potential Useful Index for Oral Cancer and the Association of miR-21 with Smoking History: a Pilot Study
Authors: Vageli Dimitra P. , Doukas Panagiotis G. , Shah Rema , Boyi Trinithas , Liu Christina , Judson Benjamin L.
Published: December 2023

Supplementary Table S2 shows healthy individuals’ characteristics, social history for risk factors and histology of oral lesion that saliva and blood (serum) were collected.
Data from A Novel Saliva and Serum miRNA Panel as a Potential Useful Index for Oral Cancer and the Association of miR-21 with Smoking History: a Pilot Study
Authors: Vageli Dimitra P. , Doukas Panagiotis G. , Shah Rema , Boyi Trinithas , Liu Christina , Judson Benjamin L.
Published: December 2023

Abstract
Tobacco use is implicated in the carcinogenesis of oral squamous cell carcinoma (OSCC), which is associated with poor survival if not diagnosed early. Identification of novel noninvasive, highly sensitive, and cost-effective diagnostic and risk assessment methods for OSCC would improve early detection. Here, we report a pilot study assessing salivary and serum miRNAs associated with OSCC and stratified by smoking status. Saliva and paired serum samples were collected from 23 patients with OSCC and 21 healthy volunteers, with an equal number of smokers and nonsmokers in each group. Twenty head and neck cancer–related miRNAs were quantified by qPCR (dual-labeled LNA probes) and analyzed by Welch t test (95% confidence interval). Four saliva miRNAs, miR-21, miR-136, miR-3928, and miR-29B, showed statistically significant overexpression in OSCC versus healthy controls (P < 0.05). miR-21 was statistically significantly overexpressed in OSCC smokers versus nonsmokers (P = 0.006). Salivary miR-21, miR-136, and miR-3928, and serum miR-21 and miR-136, showed statistically significant differential expression in early-stage tumors versus controls (P < 0.05), particularly miR-21 in smokers (P < 0.005). This pilot study provides a novel panel of saliva and serum miRNAs associated with oral cancer. Further validation as a potential useful index of oral cancer, particularly miR-21 in smokers and early-stage OSCC is warranted.
Prevention Relevance:
Saliva and serum miR-21, miR-136, miR-3928, and miR-29B, are potentially associated with oral cancer even at an early stage, especially miR-21 in individuals with a smoking history, a further validation in a larger cohort of subjects with premalignant and early malignant lesions need to confirm.
Data from Clinical Performance of hrHPV Primary Screening Using Vaginal versus Cervical Samples to Detect High-grade Intraepithelial Lesions
Authors: King Jonathan , Flores Yvonne N. , Meneses-León Joacim , Hernández-Salazar Sonia , Robles-Rivera Karina , Rivera-Paredez Berenice , León-Maldonado Leith , Hernández-López Rubí , Torres-Ibarra Leticia , Lazcano-Ponce Eduardo , Salmerón Jorge
Published: December 2023

Abstract
High-risk human papillomavirus (hrHPV) testing is now the most recommended primary method for cervical cancer screening worldwide. Clinician-collected cervical sampling continues to be the main sampling method, but hrHPV vaginal self-sampling is an appealing alternative because of its greater acceptability and potentially higher cost-effectiveness. This study aimed to determine whether hrHPV vaginal self-sampling is comparable with clinician-collected cervical sampling for detecting histologically confirmed high-grade cervical intraepithelial neoplasia (CIN2/3) as part of a cervical cancer screening program in Mexico. We analyzed data from 5,856 women screened during a hrHPV-based screening study. Clinical performance and diagnostic efficiency metrics were estimated for the two sampling methods for the CIN3 and CIN2+ endpoints, using three triage strategies: HPV16/18 genotyping, HPV16/18/33/58 extended genotyping, and HPV16/18/31/33/58 extended genotyping. hrHPV-positivity was found in 801 (13.7%) cervical and 897 (15.3%) vaginal samples. All women with hrHPV-positive samples were referred to colposcopy, which detected 17 total CIN3 cases before considering retrospective triage strategies. Using the HPV16/18/31/33/58 extended genotyping strategy, 245 women had hrHPV-positive cervical samples and 269 had hrHPV-positive vaginal samples. Ten CIN3 cases were detected each among women with hrHPV-positive cervical samples and among those with hrHPV-positive vaginal samples when using this strategy, with no significant differences in sensitivity and specificity observed. We observe that self- and clinician-collected sampling methods are comparable for detecting CIN3 and CIN2+ regardless of the triage strategy used. These findings can help public health officials to develop more cost-effective cervical cancer screening programs that maximize participation.
Prevention Relevance:
We found that hrHPV vaginal self-sampling is comparable with hrHPV clinician cervical sampling when using any triage strategy to refer women to colposcopy, so self-sampling is a viable cervical screening method. Therefore, policymakers should consider incorporating self-sampling into cervical screening programs to increase screening coverage and reduce cervical cancer burden.

See related Spotlight, p. 649
Persistent Hydrocephalus, Shunt, and Subglottic Stenosis in a Newborn with Plasminogen Deficiency due to Delayed Treatment with Plasminogen Concentrates: A Case Report
Authors: Biesinger Benedikt Stephan , Male Christoph , Kranebitter Veronika , Binder Julia , Niederle Martin B. , Reinprecht Andrea , Binder Christoph
Published: December 2023

Introduction: Here we present the case of a newborn baby boy with severe plasminogen deficiency causing occlusive hydrocephalus and ligneous conjunctivitis. Case Presentation: Shortly after birth, the hydrocephalus was treated with a ventriculoperitoneal shunt implantation. However, the child had to be readmitted soon afterward because of shunt obstruction. Subglottic microtrauma caused by the necessary intubations then led to another life-threatening complication – subglottic stenosis with pseudomembrane formation. Microsurgical removal had to be performed to secure the airway. Initially, regular plasma transfusions achieved slightly elevated plasminogen activity levels and short-term improvement of the respiratory situation. However, shunt dysfunction reoccurred, and alternative treatment options were needed. Since therapy with plasminogen concentrate is already available in the USA with encouraging results, this treatment option was organized in hopes of equally good results for this patient. Fortunately, under short-term substitution with plasminogen concentrates, the implantation of a new ventriculoperitoneal shunt was successful, and respiratory problems resolved. Conclusion: Plasminogen concentrates are critically needed in Europe and other parts of the world to improve the care of and prevent complications among patients with plasminogen deficiency.
Effect of Facemask in Congenital Central Hypoventilation Syndrome
Authors: Dudoignon Benjamin , Patout Maxime , Couque Nathalie , Delclaux Christophe , Bokov Plamen
Published: December 2023

Introduction: Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder with a mutation in the PHOX2B gene. Patients need ventilatory support by noninvasive ventilation or tracheostomy to treat alveolar hypoventilation. Patients with CCHS have a defect in chemosensitivity signal integration. Recently, due to the COVID-19 pandemic, the entire world has had to get used to wearing medical masks (MM). Objectives: The aim of the study was to evaluate the effect of an MM on gas exchange and to determine the role of central and peripheral chemoresponsiveness on the partial pressure of transcutaneous carbon dioxide (PtcCO2) in patients with CCHS wearing an MM. Methods: This study was based on the analysis of recordings obtained without and with an MM during hospitalization and was conducted to assess the impact of MM on PtcCO2 and SpO2 recordings with the SenTec Digital Monitor and their relationships with peripheral CO2 chemosensitivity obtained during tidal breathing measurement and with the hypercapnic hyperoxic ventilatory response. Results: Sixteen patients were included (13 boys) and were 10.2 (7.5; 18.5) years old. The use of an MM had a negative impact on gas exchange in patients with CCHS. The median PtcCO2 increased significantly. Peripheral chemosensitivity correlated with MM-induced PtcCO2 changes (R = −0.72, p = 0.005), but central chemosensitivity (the hypercapnic ventilator response slope) did not (R = −0.22, p = 0.510). Conclusion: The use of an MM had a negative impact on gas exchange in patients with CCHS.