bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from The Novel Polyamine Analogue CGC-11093 Enhances the Antimyeloma Activity of Bortezomib
Authors: Carew Jennifer S. , Nawrocki Steffan T. , Reddy Venudhar K. , Bush Dorothy , Rehg Jerold E. , Goodwin Andrew , Houghton Janet A. , Casero Robert A. , Marton Laurence J. , Cleveland John L.
Published: March 2023

Abstract
Multiple myeloma (MM) is an incurable plasma cell malignancy. The recent successes of the proteasome inhibitor bortezomib in MM therapy have prompted investigations of its efficacy in combination with other anticancer agents. Polyamines play important roles in regulating tumor cell proliferation and angiogenesis and represent an important therapeutic target. CGC-11093 is a novel polyamine analogue that has completed a phase I clinical trial for the treatment of cancer. Here, we report that CGC-11093 selectively augments the in vitro and in vivo antimyeloma activity of bortezomib. Specifically, the combination of CGC-11093 and bortezomib compromised MM viability and clonogenic survival, and increased drug-induced apoptosis over that achieved by either single agent. Xenografts of MM tumors treated with this combination had marked increases in phospho-c-Jun-NH2-kinase (JNK)-positive cells and apoptosis, and corresponding reductions in tumor burden, tumor vasculature, and the expression of proliferating cell nuclear antigen and the proangiogenic cytokine vascular endothelial growth factor. Furthermore, inhibition of JNK with a pharmacologic inhibitor or by selective knockdown blunted the efficacy of CGC-11093 and bortezomib. Therefore, CGC-11093 enhances the anticancer activity of bortezomib by augmenting JNK-mediated apoptosis and blocking angiogenesis. These findings support the study of the use of the combination of bortezomib and CGC-11093 in MM patients that fail to respond to frontline therapy. [Cancer Res 2008;68(12):4783–90]
Data from Semaphorin 3B Inhibits the Phosphatidylinositol 3-Kinase/Akt Pathway through Neuropilin-1 in Lung and Breast Cancer Cells
Authors: Castro-Rivera Emely , Ran Sophia , Brekken Rolf A. , Minna John D.
Published: March 2023

Abstract
Semaphorin 3B (SEMA3B), located at 3p21.3, is a secreted member of the semaphorin family important in axonal guidance. SEMA3B undergoes allele and expression loss in lung and breast cancer and can function as a tumor suppressor. Previously, we found that SEMA3B induces apoptosis in tumor cells either by reexpression or when applied as a soluble ligand. SEMA3B-induced apoptosis was mediated, in part, by blocking vascular endothelial growth factor autocrine activity in tumor cells. In the current study, treatment of lung and breast cancer cells with picomolar concentrations of soluble SEMA3B inhibited their growth; induced apoptosis; and was associated with decreased Akt phosphorylation, increase in cytochrome c release and caspase-3 cleavage, as well as increased phosphorylation of several proapoptotic proteins, including glycogen synthase kinase-3β, FKHR, and MDM-2. Lung and breast cancer lines resistant to SEMA3B did not show these signaling changes and a tumor-derived missense SEMA3B mutant was inactive in this regard, providing specificity. SEMA3B-mediated inhibition of proliferation and induction of apoptosis in cancer cells were blocked by expressing a constitutively active Akt mutant and are linked to tumor cell expression of neuropilin-1 (Np-1). SEMA3B-insensitive Np-1–negative tumor cells acquired sensitivity to SEMA3B after forced expression of Np-1, whereas SEMA3B-sensitive Np-1–positive tumor cells lost sensitivity to SEMA3B after knockdown of Np-1 by small interfering RNA. We conclude that SEMA3B is a potential tumor suppressor that induces apoptosis in SEMA3B-inactivated tumor cells through the Np-1 receptor by inactivating the Akt signaling pathway. [Cancer Res 2008;68(20):8295–303]
Data from Protein Phosphatase-2A Is a Target of Epigallocatechin-3-Gallate and Modulates p53-Bak Apoptotic Pathway
Authors: Qin Jichao , Chen He-Ge , Yan Qin , Deng Mi , Liu Jinping , Doerge Stephan , Ma Weiya , Dong Zigang , Wan-Cheng Li David
Published: March 2023

Abstract
(-)-Epigallocatechin-3-gallate (EGCG) is a well-known chemoprevention factor. Recent studies have revealed that EGCG triggers cancer cells undergoing apoptosis through p53-dependent pathway. How EGCG activates p53-dependent apoptosis is not fully understood. In the present study using JB6 cell as a model system, we have shown that EGCG can negatively regulate protein serine/threonine phosphatase-2A (PP-2A) to positively regulate p53-dependent apoptosis. First, EGCG at physiologic levels down-regulates PP-2A at the protein and enzyme activity levels. Second, EGCG induces apoptosis of JB6 cells, which is associated with hyperphosphorylation of p53 and up-regulation of the proapoptotic gene, Bak. DNA sequence analysis, gel mobility shifting, chromatin immunoprecipitation, and reporter gene activity assays revealed that p53 directly controls Bak in JB6 cells. Knockdown of p53 and Bak expression with RNAi substantially inhibits EGCG-induced apoptosis. Third, PP-2A directly interacts with p53 and dephosphorylates p53 at Ser-15 in vitro and in vivo. Fourth, overexpression of the catalytic subunit for PP-2A down-regulates p53 phosphorylation at Ser15, attenuates expression of the downstream proapoptotic gene, Bak, and antagonizes EGCG-induced apoptosis. Inhibition of PP-2A activity enhances p53 phosphorylation at Ser-15 and up-regulates Bak expression to promote EGCG-induced apoptosis. Finally, in the p53−/− H1299 and p53+/+ H1080 cells, EGCG down-regulates PP-2A similarly but induces differential apoptosis. In summary, our results show that (a) PP-2A directly dephosphorylates p53 at Ser-15; (b) P53 directly controls Bak expression; and (c) EGCG negatively regulates PP-2A. Together, our results show that EGCG-mediated negative regulation of PP-2A is an important molecular event for the activation of p53-dependent apoptosis during its chemoprevention. [Cancer Res 2008;68(11):4150–62]
Supplementary Table S6 from Randomized, Double-Blind, Placebo-Controlled Trial of MUC1 Peptide Vaccine for Prevention of Recurrent Colorectal Adenoma
Authors: Schoen Robert E. , Boardman Lisa A. , Cruz-Correa Marcia , Bansal Ajay , Kastenberg David , Hur Chin , Dzubinski Lynda , Kaufman Sharon F. , Rodriguez Luz M. , Richmond Ellen , Umar Asad , Szabo Eva , Salazar Andres , McKolanis John , Beatty Pamela , Pai Reetesh K. , Singhi Aatur D. , Jacqueline Camille M. , Bao Riuye , Diergaarde Brenda , McMurray Ryan P. , Strand Carrie , Foster Nathan R. , Zahrieh David M. , Limburg Paul J. , Finn Olivera J.
Published: March 2023

Background Information on Advanced Adenoma
Supplementary Table S4 from Randomized, Double-Blind, Placebo-Controlled Trial of MUC1 Peptide Vaccine for Prevention of Recurrent Colorectal Adenoma
Authors: Schoen Robert E. , Boardman Lisa A. , Cruz-Correa Marcia , Bansal Ajay , Kastenberg David , Hur Chin , Dzubinski Lynda , Kaufman Sharon F. , Rodriguez Luz M. , Richmond Ellen , Umar Asad , Szabo Eva , Salazar Andres , McKolanis John , Beatty Pamela , Pai Reetesh K. , Singhi Aatur D. , Jacqueline Camille M. , Bao Riuye , Diergaarde Brenda , McMurray Ryan P. , Strand Carrie , Foster Nathan R. , Zahrieh David M. , Limburg Paul J. , Finn Olivera J.
Published: March 2023

Adverse Events: Grade 2
Supplementary Tables S1-S11 from Blocking Genomic Instability Prevents Acquired Resistance to MAPK Inhibitor Therapy in Melanoma
Authors: Dharanipragada Prashanthi , Zhang Xiao , Liu Sixue , Lomeli Shirley H. , Hong Aayoung , Wang Yan , Yang Zhentao , Lo Kara Z. , Vega-Crespo Agustin , Ribas Antoni , Moschos Stergios J. , Moriceau Gatien , Lo Roger S.
Published: March 2023

Table S1: Clinical characteristics of patients who donated MAPKi-sensitive/-naive and acquired MAPKi-resistant melanoma. Table S2: Genomic alterations, chromothripsis, and ecDNA-/CGR-amplicons detected in MAPKi-sensitive/-naive and acquired MAPKi-resistant melanoma genomes. Table S3: Genes amplified by ecDNAs, CGRs, and linear amplicons along with copy numbers in MAPKi-sensitive/-naïve and acquired MAPKi-resistant melanoma genomes. Table S4: Co-occurrence of resistance-associated genetic alterations (identified in prior studies) with resistance-driver ecDNA and CGR amplicons (identified in the current study). Table S5: Normalized RNA-seq-based transcript expression in MAPKi-sensitive/-naïve and acquired-resistant tumors. Table S6: MAPK-reactivation amplicons in acquired resistance, copy numbers, and amplicon sub-types. Table S7: MAPKi-resistant genes amplified by ecDNAs and CGRs utilized for pathway enrichment analysis. Table S8: Enhancers associated with ecDNAs and CGRs in MAPKi-sensitive/-naive and acquired MAPKi-resistant melanoma genomes. Table S9: Frequencies of enriched SBS signatures reflecting defective DNA repair mechanisms within chromothripsis and non-chromothriptic regions in MAPKi-sensitive (n = 16) and acquired-resistant (n = 31) tumors. Table S10: ecDNAs, CGRs, copy numbers, and associated genes in human melanoma cell lines (M229, M249) on vehicle treatment and early on treatment. Table S11: ecDNAs, CGRs, copy numbers, associated genes in vehicle-treated and early on-treatment PDX tumors.
Supplementary Figure 6 from Persistence of Drug-Resistant Leukemic Stem Cells and Impaired NK Cell Immunity in CML Patients Depend on MIR300 Antiproliferative and PP2A-Activating Functions
Authors: Silvestri Giovannino , Trotta Rossana , Stramucci Lorenzo , Ellis Justin J. , Harb Jason G. , Neviani Paolo , Wang Shuzhen , Eisfeld Ann-Kathrin , Walker Christopher J. , Zhang Bin , Srutova Klara , Gambacorti-Passerini Carlo , Pineda Gabriel , Jamieson Catriona H. M. , Stagno Fabio , Vigneri Paolo , Nteliopoulos Georgios , May Philippa C. , Reid Alistair G. , Garzon Ramiro , Roy Denis-Claude , Moutuou Moutuaata M. , Guimond Martin , Hokland Peter , Deininger Michael W. , Fitzgerald Garrett , Harman Christopher , Dazzi Francesco , Milojkovic Dragana , Apperley Jane F. , Marcucci Guido , Qi Jianfei , Polakova Katerina Machova , Zou Ying , Fan Xiaoxuan , Baer Maria R. , Calabretta Bruno , Perrotti Danilo
Published: March 2023

Figure S6. Selective suppression of MIR300 pro-apoptotic but not anti-proliferative activity by TUG1 lncRNA in quiescent LSCs. A, BloodSpot array-based TUG1 expression levels during normal myelopoiesis and in myeloid neoplams. B, GEO Profiles show TUG1 levels in in lineage-negative (Lin-) and -positive (Lin+) CD34- and CD34human stem/progenitor cells from healthy individuals. C, Experimental data- and current literature-based graphic representation of signaling network controlling CML LSC quiescence and survival through the BMM-C/EBPbeta-MIR300 and BMM-TGFbeta-FoxM1 pathways. Dotted lines indicate inactive pathways, line thickness indicates relevance of the signal for LSC quiescence. Red lines indicate signals increasing MIR300 levels. Black lines signals increasing TUG1 levels. (bottom) effects of different TUG1 levels on CML leukemic stem (LSC) and progenitor (LPC) cell fate.
Supplementary Figure 4 from Persistence of Drug-Resistant Leukemic Stem Cells and Impaired NK Cell Immunity in CML Patients Depend on MIR300 Antiproliferative and PP2A-Activating Functions
Authors: Silvestri Giovannino , Trotta Rossana , Stramucci Lorenzo , Ellis Justin J. , Harb Jason G. , Neviani Paolo , Wang Shuzhen , Eisfeld Ann-Kathrin , Walker Christopher J. , Zhang Bin , Srutova Klara , Gambacorti-Passerini Carlo , Pineda Gabriel , Jamieson Catriona H. M. , Stagno Fabio , Vigneri Paolo , Nteliopoulos Georgios , May Philippa C. , Reid Alistair G. , Garzon Ramiro , Roy Denis-Claude , Moutuou Moutuaata M. , Guimond Martin , Hokland Peter , Deininger Michael W. , Fitzgerald Garrett , Harman Christopher , Dazzi Francesco , Milojkovic Dragana , Apperley Jane F. , Marcucci Guido , Qi Jianfei , Polakova Katerina Machova , Zou Ying , Fan Xiaoxuan , Baer Maria R. , Calabretta Bruno , Perrotti Danilo
Published: March 2023

Figure S4. MIR300 anti-proliferative activity accounts for BMM-induced LSC entry into quiescence. A, Structure of 14q32 DLK1-DIO3 genomic imprinted locus hosting the MEG3-regulated human MIR300. B, MIR300 levels in 5-Aza- or DMSO-treated (24h) Ph+ cells. C, Effect of hypoxia on proliferation of CFSE+CD34+ CML-BC cells. D, left: Effect of MSC (HS-5)-derived CM on LAMA-84 proliferation expressed as fold changes of CFSE mean of fluorescence intensity (MFI)+/-SEM; middle: pro-apoptotic effect of PAD (FTY720; 2.5uM) and DMSO (control) on HS-5-cultured LAMA-84 cells; right: Effect of MSC (HS-5)-derived CM BCR-ABL1 expression (anti-ABL1) and activity anti-PY), phospho-BCR-ABL1, JAK2 expression and activity JAK2 Y1007/1008, PP2A activity (pPP2AY307 inactive form) and GRB2 used as a control (blots are representative of three independent experiments). E, Levels of C/EBPbeta and GRB2 mRNA and protein in HS-5 cells exposed to hypoxia (48h; 1% O2). F, Effect of neutralizing TGFbeta antibody (anti-TGFb Ab; 48h, 1.25 ÃŽÂ¼g/ml) on MIR300 levels in CD34+ CML-BC cells. G, Effect of ectopic C/EBPalpha (MigR1-deltauORF-C/EBPalpha-HA) and C/EBPbeta (MigR1-C/EBPB-ERTAM) on MIR300 levels in K562 cells. Immunoblot shows levels of C/EBPbeta and GRB2 in normoxic and hypoxic K562 cells.
Supplementary Figure 2 from Persistence of Drug-Resistant Leukemic Stem Cells and Impaired NK Cell Immunity in CML Patients Depend on MIR300 Antiproliferative and PP2A-Activating Functions
Authors: Silvestri Giovannino , Trotta Rossana , Stramucci Lorenzo , Ellis Justin J. , Harb Jason G. , Neviani Paolo , Wang Shuzhen , Eisfeld Ann-Kathrin , Walker Christopher J. , Zhang Bin , Srutova Klara , Gambacorti-Passerini Carlo , Pineda Gabriel , Jamieson Catriona H. M. , Stagno Fabio , Vigneri Paolo , Nteliopoulos Georgios , May Philippa C. , Reid Alistair G. , Garzon Ramiro , Roy Denis-Claude , Moutuou Moutuaata M. , Guimond Martin , Hokland Peter , Deininger Michael W. , Fitzgerald Garrett , Harman Christopher , Dazzi Francesco , Milojkovic Dragana , Apperley Jane F. , Marcucci Guido , Qi Jianfei , Polakova Katerina Machova , Zou Ying , Fan Xiaoxuan , Baer Maria R. , Calabretta Bruno , Perrotti Danilo
Published: March 2023

Figure S2. KEGG/GO analysis of MIR300 on PP2A-regulated signal transduction pathways. Cartoon shows the SET-dependent PP2A Inhibitory pathway in CML and the pleiotropic inhibitory effect of PP2A activation on validated and predicted MIR300 targets regulating G1/S cell cycle transition, Wnt-beta-catenin, TGFbeta, JAK-STAT, PI-3K-Akt, RAS-MAPK and Notch signaling pathways.
Table TS2 from IL1β Expression Driven by Androgen Receptor Absence or Inactivation Promotes Prostate Cancer Bone Metastasis
Authors: DiNatale Anthony , Worrede Asurayya , Iqbal Waleed , Marchioli Michael , Toth Allison , Sjöström Martin , Zhu Xiaolin , Corey Eva , Feng Felix Y. , Zhou Wanding , Fatatis Alessandro
Published: March 2023

Whole genome bisulfite sequencing conducted on a subset of patients with low AR activity and low IL-1β expression revealed 346 CpG sites spanning the IL-1β promoter and gene body on chromosome 2, of which 34 showed significant differences in methylation when comparing patients with similarly low AR activity but having high vs. low expression of IL-1β.
Supplementary Tables S1-9 from Predictive and Prognostic Implications of Circulating CX3CR1+ CD8+ T Cells in Non–Small Cell Lung Cancer Patients Treated with Chemo-Immunotherapy
Authors: Abdelfatah Eihab , Long Mark D. , Kajihara Ryutaro , Oba Takaaki , Yamauchi Takayoshi , Chen Hongbin , Sarkar Joy , Attwood Kristopher , Matsuzaki Junko , Segal Brahm H. , Dy Grace K. , Ito Fumito
Published: March 2023

Supplementary Tables 1-9
Supplementary Figure S2 from Predictive and Prognostic Implications of Circulating CX3CR1+ CD8+ T Cells in Non–Small Cell Lung Cancer Patients Treated with Chemo-Immunotherapy
Authors: Abdelfatah Eihab , Long Mark D. , Kajihara Ryutaro , Oba Takaaki , Yamauchi Takayoshi , Chen Hongbin , Sarkar Joy , Attwood Kristopher , Matsuzaki Junko , Segal Brahm H. , Dy Grace K. , Ito Fumito
Published: March 2023

Supplementary Figure 2. Baseline (high vs. low) frequency of peripheral blood (PB) CX3CR1+ CD8+ T cells does not associate with response and prognosis in NSCLC patients undergoing chemo-immunotherapy. Related to Fig. 1 Overall response rate (ORR), progression free survival (PFS), and overall survival (OS) of patients with high and low pre-treatment frequency of the CX3CR1+ subset in PB CD8+ T cells at various cut-off points. P values were calculated by a log-rank (Mantel-Cox) test.
Supplementary Figure S1 from Predictive and Prognostic Implications of Circulating CX3CR1+ CD8+ T Cells in Non–Small Cell Lung Cancer Patients Treated with Chemo-Immunotherapy
Authors: Abdelfatah Eihab , Long Mark D. , Kajihara Ryutaro , Oba Takaaki , Yamauchi Takayoshi , Chen Hongbin , Sarkar Joy , Attwood Kristopher , Matsuzaki Junko , Segal Brahm H. , Dy Grace K. , Ito Fumito
Published: March 2023

Supplementary Figure 1: Single-cell RNA/TCR sequencing (scRNA/TCR-seq) quality assessment. A Gating strategy of identifying single live CD45+CD19–CD3+CD56– cells from cryopreserved peripheral mononuclear blood cells for scRNA/TCR-seq. B Representative flow cytometric plots showing the frequency of CD45+CD19–CD3+CD56– cells after flow-sort. C Scatterplots depicting total features, counts, doublet scores, mitochondrial content and ribosomal content across all cells prior to filtering. Filtering thresholds applied are shown. D Elbow plot of PCA (top 50 components). PC selection for downstream analysis was limited to those components accounting for at least 0.1 % of total variation (n = 44). E UMAP representations of all-post filtered, normalized cells showing cellular distributions of total unique counts, mitochondrial scores, ribosomal scores, G2M/S phase scores and doublet scores. F UMAP plot identifying doublets by hashtag oligos (HTO).
Table TS1 from IL1β Expression Driven by Androgen Receptor Absence or Inactivation Promotes Prostate Cancer Bone Metastasis
Authors: DiNatale Anthony , Worrede Asurayya , Iqbal Waleed , Marchioli Michael , Toth Allison , Sjöström Martin , Zhu Xiaolin , Corey Eva , Feng Felix Y. , Zhou Wanding , Fatatis Alessandro
Published: March 2023

Primer sequences used for ChIP assay
Supplementary Fig. S5 from The PARP1 Inhibitor AZD5305 Impairs Ovarian Adenocarcinoma Progression and Visceral Metastases in Patient-derived Xenografts Alone and in Combination with Carboplatin
Authors: Dellavedova Giulia , Decio Alessandra , Formenti Laura , Albertella Mark R. , Wilson Joanne , Staniszewska Anna D. , Leo Elisabetta , Giavazzi Raffaella , Ghilardi Carmen , Bani Maria Rosa
Published: March 2023

Fig. S5 shows the effect of AZD5305 on the OC-PDX HOC22
Figure S2 from IL1β Expression Driven by Androgen Receptor Absence or Inactivation Promotes Prostate Cancer Bone Metastasis
Authors: DiNatale Anthony , Worrede Asurayya , Iqbal Waleed , Marchioli Michael , Toth Allison , Sjöström Martin , Zhu Xiaolin , Corey Eva , Feng Felix Y. , Zhou Wanding , Fatatis Alessandro
Published: March 2023

Expression of CMV-AR and TRE-AR constructs in PC3-ML cells, confirmed at the transcript level for both (a) and at the protein level for the TRE-AR following addition of doxycycline to the culture medium (b).
Figure S1 from IL1β Expression Driven by Androgen Receptor Absence or Inactivation Promotes Prostate Cancer Bone Metastasis
Authors: DiNatale Anthony , Worrede Asurayya , Iqbal Waleed , Marchioli Michael , Toth Allison , Sjöström Martin , Zhu Xiaolin , Corey Eva , Feng Felix Y. , Zhou Wanding , Fatatis Alessandro
Published: March 2023

C4-2B cells exposed to Enzalutamide show a dose-dependent(a) and time- dependent increase in IL-1β expression (b). Removal of enzalutamide after a 15-day treatment resulted in a return of IL-1β expression to control (undetectable) levels (c). Same results were obtained with 15-day hormone-deprivation followed by DHT re-addition (d).
Supplementary Table S2 from CD142 identifies neoplastic desmoid tumor cells, uncovering interactions between neoplastic and stromal cells that drive proliferation
Authors: Al-Jazrawe Mushriq , Xu Steven , Poon Raymond , Wei Qingxia , Przybyl Joanna , Varma Sushama , van de Rijn Matt , Alman Benjamin
Published: March 2023

Enriched markers in mutant and non-mutant colonies from our high throughput surface antigen screen.
Supplementary Figure S8 from CD142 identifies neoplastic desmoid tumor cells, uncovering interactions between neoplastic and stromal cells that drive proliferation
Authors: Al-Jazrawe Mushriq , Xu Steven , Poon Raymond , Wei Qingxia , Przybyl Joanna , Varma Sushama , van de Rijn Matt , Alman Benjamin
Published: March 2023

Co-culturing of mutant desmoid tumor cells with non-mutant fibroblasts increases their proliferation rate
Supplementary Figure S4 from CD142 identifies neoplastic desmoid tumor cells, uncovering interactions between neoplastic and stromal cells that drive proliferation
Authors: Al-Jazrawe Mushriq , Xu Steven , Poon Raymond , Wei Qingxia , Przybyl Joanna , Varma Sushama , van de Rijn Matt , Alman Benjamin
Published: March 2023

Podoplanin-based flow cytometry of mutant and non-mutant colonies.
Supplementary Figure S2 from CD142 identifies neoplastic desmoid tumor cells, uncovering interactions between neoplastic and stromal cells that drive proliferation
Authors: Al-Jazrawe Mushriq , Xu Steven , Poon Raymond , Wei Qingxia , Przybyl Joanna , Varma Sushama , van de Rijn Matt , Alman Benjamin
Published: March 2023

Detection of potential morphological differences between colonies derived from the same desmoid tumor primary culture sample
Supplementary Figure S10 from CD142 identifies neoplastic desmoid tumor cells, uncovering interactions between neoplastic and stromal cells that drive proliferation
Authors: Al-Jazrawe Mushriq , Xu Steven , Poon Raymond , Wei Qingxia , Przybyl Joanna , Varma Sushama , van de Rijn Matt , Alman Benjamin
Published: March 2023

Densitometry of selected secreted proteome from mutant and non-mutant conditioned media
Data from The PARP1 Inhibitor AZD5305 Impairs Ovarian Adenocarcinoma Progression and Visceral Metastases in Patient-derived Xenografts Alone and in Combination with Carboplatin
Authors: Dellavedova Giulia , Decio Alessandra , Formenti Laura , Albertella Mark R. , Wilson Joanne , Staniszewska Anna D. , Leo Elisabetta , Giavazzi Raffaella , Ghilardi Carmen , Bani Maria Rosa
Published: March 2023

PARP inhibitors (PARPi) have changed the management of patients with ovarian cancer and their effectiveness has been demonstrated especially in homologous recombination repair–deficient tumors. These first-generation drugs target PARP1, but also PARP2 and other family members potentially responsible for adverse effects that limit their therapeutic potential and restrict their use in combination with chemotherapeutic agents.

We investigated ovarian cancer patient-derived xenografts (OC-PDXs) to assess whether malignant progression could be impaired by a novel inhibitor selective for PARP1 (AZD5305) and to assess the potential of its combination with carboplatin (CPT), the standard-of-care for patients with ovarian cancer.

In BRCA-mutated OC-PDXs, AZD5305 achieved greater tumor regressions and longer duration of response as well as a superior impairment of visceral metastasis and improved survival benefit compared with the first-generation dual PARP1/2 inhibitors.

The combination of AZD5305 plus CPT was more efficacious than single agents. Subcutaneously growing tumors experienced regression that persisted after therapy stopped. Combination efficacy was greater against tumors that did not respond well to platinum, even at a dose at which AZD5305 monotherapy was ineffective. The combination therapy impaired metastatic dissemination and significantly prolonged the lifespan of mice bearing OC-PDXs in their abdomen. This combination benefit was evident even when CPT was used at suboptimal doses, and was superior to full-dose platinum treatment.

These preclinical studies demonstrate that the PARP1-selective inhibitor AZD5305 retains and improves the therapeutic benefit of the first-generation PARPi, providing an opportunity to maximize benefits for this class of anticancer agents.
Significance:
Selective PARP1i AZD5305 can exceed the efficacy of first-generation PARPi, which target both PARP1 and PARP2, and potentiates the efficacy of CPT when given in combination. AZD5305 alone or in combination with platinum delayed visceral metastasis, ultimately extending the lifespan of OC-PDX–bearing mice. These preclinical models mimic the progression of the disease occurring in patients after debulking surgery, and are translationally relevant.
The Role of Social Media and Breast Cancer: How Does It Impact Patients?
Authors: Gandamihardja Tasha AK , Liyanage Sara , Coutee Terri , Peled Anne W , Masannat Yazan A
Published: March 2023

Introduction: Patients are increasingly turning to other sources for their health information. Social media has become mainstream, and the easy access to online communities, health professionals, and shared experiences of other patients has made social media a place where many patients turn to. Methods: In this qualitative report, 2 patients who have had breast cancer describe the reasons why they use social media, what they perceive the advantages and disadvantages are, and what the impact of social media has been through their cancer treatment and beyond. Results: The reasons why patients turn to social media are varied. These can include information gathering, peer support, shared experiences, and advocacy. There appear to be advantages and disadvantages; however, overall, the impact seems to be a positive one when used judiciously. Discussion: It is clear that social media has a role to play in healthcare, whether by providing meaningful social connections, delivery of information, or psychological support. Healthcare professionals perhaps should consider the importance of social media in their practice.
Multi-suture craniosynostosis in Sotos Syndrome: A case Report
Authors: Al-Shaqsi Sultan , Forrest Christopher R.
Published: March 2023

Study Design

Case report.

Objective

Sotos syndrome is a rare genetic disorder which is characterized by excessive physical growth during the first few years of life. The principal features of this condition include macrocephaly, learning disability and physical overgrowth. The current diagnosis of Sotos Syndrome is based on identification of genetic mutations and deletions in the NSD family (the Nuclear-receptor-binding SET-Domain containing protein). Single suture craniosynostosis has been reported in a few cases of Sotos syndrome. We report an atypical presentation of multi-suture craniosynostosis in a child with Sotos Syndrome.

Methods

The initial phenotypical presentation was consistent with left coronal craniosynostosis. She underwent strip suturectomy and orthotic helmeting with failure to correct her anterior plagiocephaly and orbital dysmorphology. Additional post-operative investigations revealed a multi-suture craniosynostosis. She subsequently underwent an anterior cranial vault reconstruction and fronto-orbital advancement.

Conclusions

Sotos Syndrome can be associated with single or multi-suture craniosynostosis. This is likely driven by the overgrowth status of this disease. In our case report, the patient presents with unicoronal craniosynostosis which progressed to multi-suture craniosynostosis. Therefore, a multidisciplinary approach and close monitoring by craniofacial surgeons, neurosurgeons, developmental paediatricians and other allied teams is required in the care of such patients.
Using red blood cell distribution width to predict death after abdominal aortic aneurysm rupture
Authors: Li Wanghai , Liao Tao , Zhang Yan , Li Chengzhi
Published: March 2023

Background

An abdominal aortic aneurysm is a life-threatening enlargement in the major vessel at the abdomen level. This study investigated the associations between different levels of red blood cell distribution width and all-cause mortality among patients with abdominal aortic aneurysm rupture. It developed predictive models for all-cause mortality risk.

Methods

This was a retrospective cohort study using 2001 to 2012 MIMIC-III dataset. The study sample included 392 U.S. adults with abdominal aortic aneurysms who were admitted to ICU after the aneurysm rupture. Then we used two single-factor and four multivariable logistic regression models to examine the associations between different levels of red blood cell distribution and all-cause mortality (30 days and 90 days), controlling for demographics, comorbidities, vital signs, and other laboratory measurements. The receiver operator characteristic curves were calculated, and the areas under the curves were recorded.

Results

There were 140 (35.7%) patients with an abdominal aortic aneurysm in the red blood cell distribution width range between 11.7 and 13.8%, 117 (29.8%) patients in the range between 13.9 and 14.9%, and 135 (34.5%) patients in the range between 15.0 and 21.6%. Patients with higher red blood cell distribution width level (> 13.8%) tended to have a higher mortality rate (both 30 days and 90 days), congestive heart failure, renal failure, coagulation disorders, lower hemoglobin, hematocrit, MCV, red blood cell count, higher levels of chloride, creatinine, sodium, and BUN (All P < 0.05). Results of multivariate logistic regression models indicated that patients with higher red blood cell distribution width levels (> 13.8%) had the highest statistically significant odd ratios of 30 days and 90 days of all-cause mortality than lower red blood cell distribution width levels. The area under the RDW curve was lower (P = 0.0009) than that of SAPSII scores.

Conclusions

Our study found that patients with abdominal aortic aneurysm rupture with a higher blood cell distribution had the highest risk of all-cause mortality. Using the blood cell distribution width level in patients with abdominal aortic aneurysm rupture to predict mortality should be considered in future clinical practice.
Streptococcus dysgalactiae subsp. dysgalactiae presents with progressive weakness in limbs: a case report and literature review
Authors: He Chen-Hong , Feng Shu-Fan , Chen Shu-Xin , Han Deng-Ke , He Tian-Rong , Cao Jian-Wei , Mai Hui-Qiang
Published: March 2023

Background

Streptococcus dysgalactiae subsp. dysgalactiae has been identified as an animal pathogen that is thought to occur only in animal populations. Between 2009 and 2022, humans infected with SDSD were reported rarely. There is a lack of details on the natural history, clinical features, and management of disease caused by this pathogen. This case outlines a human SDSD with muscle aches and progressive loss of muscle strength leading to immobility and multi-organ dysfunction syndrome.

Case presentation

She presented with muscle pain and weakness, and later developed a sore throat, headache and fever with a maximum temperature of 40.5 °C. The muscle strength of the extremities gradually decreased to grade 1 and the patient was unable to move on his own. Next-generation blood sequencing and multi-culture confirmed the presence of Streptococcus dysgalactiae and Streptococcus dysgalactiae subsp. Dysgalactiae, respectively. A Sequential Organ Failure Assessment score of 6 indicated septicemia, and therapeutic antibiotics were prescribed empirically. After 19 days of inpatient treatment, the patient's condition greatly improved and completely recovered within a month.

Conclusion

Symptoms of Streptococcus dysgalactiae subsp. dysgalactiae presenting with progressive limb weakness resemble polymyositis, so a precise differential diagnosis is essential. Multidisciplinary consultation is helpful when polymyositis cannot be ruled out and facilitates the choice of an optimal treatment protocol. In the context of this case, penicillin is an effective antibiotic for Streptococcus dysgalactiae subsp. dysgalactiae infection.
Occult intraocular aluminium foreign body causing rhegmatogenous retinal detachment: a case report
Authors: Zhang Ling , Chen Bin , He WeiMin
Published: March 2023

Background

Ocular trauma is complex and varied, and some occult intraocular foreign bodies (IOFBs) can lead to uncommon symptoms and signs. We report a case of rhegmatogenous retinal detachment (no obvious wound, no pain, no intraocular infection or other symptoms) caused by an occult intraocular aluminium foreign body, which could have been easily missed.

Case presentation

A 42-year-old male presented to the outpatient department of our hospital complaining of fluttering black dots and decreased vision in his left eye that began 3 months earlier. He was diagnosed with "floaters" at a community hospital. He denied a history of ocular trauma or previous surgery. The cornea and lens of the left eye were clear. A small patch of pigmentation was noted in the temporal sclera. Fundoscopy revealed macula-off retinal detachment. After mydriasis, elliptical holes were seen in the peripheral retina at 2:30, and a suspicious hyperreflective strip was found under the anterior lip of the retina by Goldmann three-mirror contact lens examination; the strip was confirmed to be an IOFB by orbital CT. The IOFB was removed through pars plana vitrectomy without any complications.

Conclusion

Unlike iron and copper IOFBs, aluminium IOFBs are more inert and more likely to be missed. For people with special occupations (construction workers, mechanics, etc.), when abnormal pigmentation of the sclera is found, the possibility of foreign bodies in the eye should be considered. In the process of disease diagnosis and treatment, it is necessary to ask for a detailed history, including occupation history and practice, and perform careful physical and targeted examinations. Such comprehensive analysis regarding the above information will minimize the chance of missed diagnosis.Awareness of occult IOFB in high risk occupations and prompt referral to a retinal surgeon is of outmost importance.
A comprehensive perspective of autistic traits and catatonic symptoms in a patient with Fronto-Temporal Dementia and Bipolar Disorder: a case report
Authors: Dell’Osso Liliana , Chiarantini Ilaria , Bonelli Chiara , Cappellato Gabriele , Carpita Barbara
Published: March 2023

Background

Fronto-Temporal Dementia (FTD) is a neurodegenerative disorder featuring frontotemporal lobe atrophy which leads to profound changes in behavior and cognition in the affected subjects. Considering that the onset of this type of dementia is typically characterized by the development of affective symptoms, differential diagnosis between FTD and Bipolar Disorder (BD) is particularly difficult. An important overlapping feature between BD and FTD is the presence of catatonic symptoms: Catatonia is extremely frequent in FTD, and, on the other hand, BD is the psychiatric disease with the highest frequency of association with catatonic states. In this framework, it should be noted that also Autism Spectrum conditions have been reported to show high rates of comorbidity and overlapping features with BD. In addition, subjects with autistic traits were reported to show an increased vulnerability towards the development of mood and anxiety disorders, as well as increase the risk of mood episodes with mixed features, suicidal thoughts and catatonic symptoms.

Case presentation

We reported the case of a patient with a diagnosis of both BD and FTD who showed catatonic symptoms.

Objectives

The aim of this case report is to evaluate the possible role of autistic traits in the illness trajectory of BD and FTD.

Conclusion

This case confirms the presence of a continuum between psychiatric and neurological conditions, which should be considered as expressions of a same neurobiological system and further investigated in light of an integrative model.
Effect of a new type of head and neck fixation and traction device in the surgical treatment of patients with irreducible atlantoaxial dislocation
Authors: He Haiyi , Li Xiang , Li Peng , Zhang Kai , Zhang Pengfei , Guo Qiang , Dong Cheng , Guo Gaosheng , Nie Fuxiang , Du Juan
Published: March 2023

Background

In order to improve the clinical medical technology, enhance the clinical effect and improve the disease detection rate, the clinical incidence rate of atlantoaxial dislocation and vertebral body malformation that are difficult to summarize is increasing year by year.

Methods

A total of 80 patients with atlantoaxial dislocation deformity treated in our hospital from January 2017 to May 2021 are selected for this study. According to the number table method, 80 patients are randomly divided into the auxiliary group and the traditional group, with 40 cases in each group. The traditional group is treated with posterior atlantoaxial pedicle screw system internal fixation and intervertebral fusion, and the auxiliary implementation and application of a new head and neck fixation and traction device through nasal cannula and oral release decompression fixation for posterior fusion. The patients in the two groups are compared changes and differences in efficacy, spinal cord function index, pain score, surgery, and quality of life.

Results

Compared with the traditional group, the total clinical effective rate, cervical spine extension and flexion range of motion, physical function, physical function, psychological function, and social function in the auxiliary group are significantly improved. The operation time, intraoperative blood loss, and VAS score are significantly reduced (P < 0.05).

Conclusion

The new head and neck fixation traction device can improve the surgical efficacy and quality of life of patients with irreversible atlantoaxial dislocation, enhance spinal cord function, reduce pain symptoms and surgical risks, and is worthy of clinical application.
Dermatology residents as educators: a qualitative study of identity formation
Authors: Alwazzan Lulu , AlHarithy Ruaa , Alotaibi Hend M , Kattan Thuraya , Alnasser Monira , AlNojaidi Taif
Published: March 2023

Background

One of the many identities a physician comes to form during their career is their identity as an educator. Exploring formation of this identity may enrich our understanding of how physicians make decisions related to their roles as educators, their behaviors, and how this ultimately influences the educational environment. It is the aim of this study to investigate educator identity formation of dermatology residents while early in their careers.

Methods

Drawing on a social constructionist paradigm, we conducted a qualitative study, utilizing an interpretative approach. We examined longitudinal data over a 12-month period using dermatology residents’ written reflections from their professional portfolios and semi-structured interviews. We collected this data as we progressed through and beyond a 4-month professional development program designed to encourage residents’ growth as educators. Sixty residents in their second, third, or final year of residency programs located in Riyadh, Saudi Arabia were invited to take part in this study. Twenty residents participated with sixty written reflections and 20 semi-structured interviews. Qualitative data were analyzed using a thematic analysis approach.

Results

Sixty written reflections and 20 semi-structured interviews were analyzed. Data was categorized according to themes corresponding to the original research questions. For the first research question regarding identity formation, themes included definitions of education, the process of education, and identity development. For the second research question, 1 theme entitled professional development program included, the following sub-themes: individual act, interpersonal activity, and an organizational undertaking, with many believing that residency programs should prepare residents for their educator roles. Participants also described newfound leadership ambitions of creating new dermatology fellowship programs as a result of taking part in the Resident-as-Educator program.

Conclusions

Our study provides insights on the dynamic formation of educator identities amongst dermatology residents. Investment in developing residents as educators through professional development programs may instigate transformational change on the individual physician level and profession’s level.
Clarification of ethical principle of the beneficence in nursing care: an integrative review
Authors: Cheraghi Rozita , Valizadeh Leila , Zamanzadeh Vahid , Hassankhani Hadi , Jafarzadeh Anahita
Published: March 2023

Background

Ethics-based nursing practice can transform health care practices. As the biggest human capital in the health care system, nurses are obliged to follow ethical principles in this field. One of these ethical principles; is beneficence, which is considered the core of nursing care. This study aimed to investigate clarification of the principle of beneficence in nursing care and its related challenges.

Methods

This integrative review was conducted using the Whittemore & Knafl method in 5 stages, including problem identification, searching the literature, evaluating primary sources, analyzing data, and presenting the results. Databases like SID, Irandoc, Magiran, Google Scholar, Web of Science, PubMed, and Scopus were searched using the keywords; “beneficence”, “ethic”, “nursing” and “care” in English and Persian in the time range of 2010 to 10 February, 2023. After applying inclusion criteria and assessing the articles using Bowling’s Quality Assessment Tool, finally, 16 papers were included from 984.

Results

After reviewing and evaluating the qualified articles, the findings were classified into four main categories: (1) nature, (2) applicability, (3) Relevant and influential factors, and (4) challenges related to the ethical principle of beneficence in nursing care.

Conclusion

Based on the results of this review it seems that paying attention to clarification the principle of beneficence in nursing care can provide positive outcomes for patients to benefit from this principle and finally, it leads to increasing the well-being and health of patients, reducing their mortality rate, increasing satisfaction and maintaining the respect and human dignity of patients.
Investigating rapid diagnostic testing in Kenya’s health system, 2018–2020: validating non-reporting in routine data using a health facility service assessment survey
Authors: Moturi Angela K , Robert Bibian N , Bahati Felix , Macharia Peter M , Okiro Emelda A
Published: March 2023

Background

Understanding the availability of rapid diagnostic tests (RDTs) is essential for attaining universal health care and reducing health inequalities. Although routine data helps measure RDT coverage and health access gaps, many healthcare facilities fail to report their monthly diagnostic test data to routine health systems, impacting routine data quality. This study sought to understand whether non-reporting by facilities is due to a lack of diagnostic and/or service provision capacity by triangulating routine and health service assessment survey data in Kenya.

Methods

Routine facility-level data on RDT administration were sourced from the Kenya health information system for the years 2018–2020. Data on diagnostic capacity (RDT availability) and service provision (screening, diagnosis, and treatment) were obtained from a national health facility assessment conducted in 2018. The two sources were linked and compared obtaining information on 10 RDTs from both sources. The study then assessed reporting in the routine system among facilities with (i) diagnostic capacity only, (ii) both confirmed diagnostic capacity and service provision and (iii) without diagnostic capacity. Analyses were conducted nationally, disaggregated by RDT, facility level and ownership.

Results

Twenty-one per cent (2821) of all facilities expected to report routine diagnostic data in Kenya were included in the triangulation. Most (86%) were primary-level facilities under public ownership (70%). Overall, survey response rates on diagnostic capacity were high (> 70%). Malaria and HIV had the highest response rate (> 96%) and the broadest coverage in diagnostic capacity across facilities (> 76%). Reporting among facilities with diagnostic capacity varied by test, with HIV and malaria having the lowest reporting rates, 58% and 52%, respectively, while the rest ranged between 69% and 85%. Among facilities with both service provision and diagnostic capacity, reporting ranged between 52% and 83% across tests. Public and secondary facilities had the highest reporting rates across all tests. A small proportion of health facilities without diagnostic capacity submitted testing reports in 2018, most of which were primary facilities.

Conclusion

Non-reporting in routine health systems is not always due to a lack of capacity. Further analyses are required to inform other drivers of non-reporting to ensure reliable routine health data.
Characterization of prehospital time delay in primary percutaneous coronary intervention for acute myocardial infarction: analysis of geographical infrastructure-dependent and -independent components
Authors: Oyatani Keisuke , Koyama Masayuki , Himuro Nobuaki , Miura Tetsuji , Ohnishi Hirofumi
Published: March 2023

Background

Prehospital delay in reaching a percutaneous coronary intervention (PCI) facility is a major problem preventing early coronary reperfusion in patients with ST-elevation myocardial infarction (STEMI). The aim of this study was to identify modifiable factors that contribute to the interval from symptom onset to arrival at a PCI-capable center with a focus on geographical infrastructure-dependent and -independent factors.

Methods

We analyzed data from 603 STEMI patients who received primary PCI within 12 h of symptom onset in the Hokkaido Acute Coronary Care Survey. We defined onset-to-door time (ODT) as the interval from the onset of symptoms to arrival at the PCI facility and we defined door-to-balloon time (DBT) as the interval from arrival at the PCI facility to PCI. We analyzed the characteristics and factors of each time interval by type of transportation to PCI facilities. In addition, we used geographical information system software to calculate the minimum prehospital system time (min-PST), which represents the time required to reach a PCI facility based on geographical factors. We then subtracted min-PST from ODT to find the estimated delay-in-arrival-to-door (eDAD), which represents the time required to reach a PCI facility independent of geographical factors. We investigated the factors related to the prolongation of eDAD.

Results

DBT (median [IQR]: 63 [44, 90] min) was shorter than ODT (median [IQR]: 104 [56, 204] min) regardless of the type of transportation. However, ODT was more than 120 min in 44% of the patients. The min-PST (median [IQR]: 3.7 [2.2, 12.0] min) varied widely among patients, with a maximum of 156 min. Prolongation of eDAD (median [IQR]: 89.1 [49, 180] min) was associated with older age, absence of a witness, onset at night, no emergency medical services (EMS) call, and transfer via a non-PCI facility. If eDAD was zero, ODT was projected to be less than 120 min in more than 90% of the patients.

Conclusions

The contribution of geographical infrastructure-dependent time in prehospital delay was substantially smaller than that of geographical infrastructure-independent time. Intervention to shorten eDAD by focusing on factors such as older age, absence of a witness, onset at night, no EMS call, and transfer via a non-PCI facility appears to be an important strategy for reducing ODT in STEMI patients. Additionally, eDAD may be useful for evaluating the quality of STEMI patient transport in areas with different geographical conditions.