bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from A Gene Signature Predicting for Survival in Suboptimally Debulked Patients with Ovarian Cancer
Authors: Bonome Tomas , Levine Douglas A. , Shih Joanna , Randonovich Mike , Pise-Masison Cindy A. , Bogomolniy Faina , Ozbun Laurent , Brady John , Barrett J. Carl , Boyd Jeff , Birrer Michael J.
Published: March 2023

Abstract
Despite the existence of morphologically indistinguishable disease, patients with advanced ovarian tumors display a broad range of survival end points. We hypothesize that gene expression profiling can identify a prognostic signature accounting for these distinct clinical outcomes. To resolve survival-associated loci, gene expression profiling was completed for an extensive set of 185 (90 optimal/95 suboptimal) primary ovarian tumors using the Affymetrix human U133A microarray. Cox regression analysis identified probe sets associated with survival in optimally and suboptimally debulked tumor sets at a P value of <0.01. Leave-one-out cross-validation was applied to each tumor cohort and confirmed by a permutation test. External validation was conducted by applying the gene signature to a publicly available array database of expression profiles of advanced stage suboptimally debulked tumors. The prognostic signature successfully classified the tumors according to survival for suboptimally (P = 0.0179) but not optimally debulked (P = 0.144) patients. The suboptimal gene signature was validated using the independent set of tumors (odds ratio, 8.75; P = 0.0146). To elucidate signaling events amenable to therapeutic intervention in suboptimally debulked patients, pathway analysis was completed for the top 57 survival-associated probe sets. For suboptimally debulked patients, confirmation of the predictive gene signature supports the existence of a clinically relevant predictor, as well as the possibility of novel therapeutic opportunities. Ultimately, the prognostic classifier defined for suboptimally debulked tumors may aid in the classification and enhancement of patient outcome for this high-risk population. [Cancer Res 2008;68(13):5478–86]
Data from αvβ6 Integrin Promotes the Invasion of Morphoeic Basal Cell Carcinoma through Stromal Modulation
Authors: Marsh Daniel , Dickinson Sarah , Neill Graham W. , Marshall John F. , Hart Ian R. , Thomas Gareth J.
Published: March 2023

Abstract
Basal cell carcinoma (BCC) is the most prevalent cancer in the Western world and its incidence is increasing. The pathogenesis of BCC involves deregulated Sonic hedgehog signaling, leading to activation of the Gli transcription factors. Most BCCs have a nodular growth pattern, and are indolent, slow-growing, and considered “low-risk” lesions. In contrast, the “high-risk” morphoeic variant, which causes significant morbidity, has an infiltrative growth pattern, and is so-called because of its densely fibrous stroma. As αvβ6 is capable of promoting both carcinoma invasion and fibrosis, we examined the expression of this integrin in BCCs and found that the morphoeic type showed significantly higher αvβ6 expression than the nodular type (P = 0.0009). In order to examine the function of αvβ6, we transfected the transcription factors Gli1 or Gli2 into NTERT, human keratinocytes to generate a BCC model. These cells expressed αvβ6 and were invasive, although inhibition of αvβ6 had no direct effect on cell invasion. However, the cells showed αvβ6-dependent activation of transforming growth factor-β1, which induced transdifferentiation of human fibroblasts into myofibroblasts. Paracrine secretion of hepatocyte growth factor/scatter factor by these myofibroblasts promoted c-Met–dependent tumor invasion in both Transwell and three-dimensional organotypic assays. These experimental in vitro findings were confirmed using human clinical samples in which we showed that the stroma of morphoeic BCC is myofibroblast-rich compared with nodular BCC (P = 0.0036), that myofibroblasts express hepatocyte growth factor/scatter factor, and that morphoeic BCCs are strongly c-Met–positive. These data suggest that αvβ6-dependent transforming growth factor-β1 activation induces both the infiltrative growth pattern and fibrotic stroma so characteristic of morphoeic BCC. [Cancer Res 2008;68(9):3295–303]
Data from Indirect Macrophage Responses to Ionizing Radiation: Implications for Genotype-Dependent Bystander Signaling
Authors: Coates Philip J. , Rundle Jana K. , Lorimore Sally A. , Wright Eric G.
Published: March 2023

Abstract
In addition to the directly mutagenic effects of energy deposition in DNA, ionizing radiation is associated with a variety of untargeted and delayed effects that result in ongoing bone marrow damage. Delayed effects are genotype dependent with CBA/Ca mice, but not C57BL/6 mice, susceptible to the induction of damage and also radiation-induced acute myeloid leukemia. Because macrophages are a potential source of ongoing damaging signals, we have determined their gene expression profiles and we show that bone marrow–derived macrophages show widely different intrinsic expression patterns. The profiles classify macrophages derived from CBA/Ca mice as M1-like (pro-inflammatory) and those from C57BL/6 mice as M2-like (anti-inflammatory); measurements of NOS2 and arginase activity in normal bone marrow macrophages confirm these findings. After irradiation in vivo, but not in vitro, C57BL/6 macrophages show a reduction in NOS2 and an increase in arginase activities, indicating a further M2 response, whereas CBA/Ca macrophages retain an M1 phenotype. Activation of specific signal transducer and activator of transcription signaling pathways in irradiated hemopoietic tissues supports these observations. The data indicate that macrophage activation is not a direct effect of radiation but a tissue response, secondary to the initial radiation exposure, and have important implications for understanding genotype-dependent responses and the mechanisms of the hemotoxic and leukemogenic consequences of radiation exposure. [Cancer Res 2008;68(2):450–6]
Data from The Polycomb Gene Product BMI1 Contributes to the Maintenance of Tumor-Initiating Side Population Cells in Hepatocellular Carcinoma
Authors: Chiba Tetsuhiro , Miyagi Satoru , Saraya Atsunori , Aoki Ryutaro , Seki Atsuyoshi , Morita Yohei , Yonemitsu Yutaka , Yokosuka Osamu , Taniguchi Hideki , Nakauchi Hiromitsu , Iwama Atsushi
Published: March 2023

Abstract
Side population (SP) cell analysis and sorting have been successfully applied to hepatocellular carcinoma (HCC) cell lines to identify a minor cell population with cancer stem cell properties. However, the molecular mechanisms operating in SP cells remain unclear. The polycomb gene product BMI1 plays a central role in the self-renewal of somatic stem cells in a variety of tissues and organs and seems to be implicated in tumor development. In this study, we determined the critical role of BMI1 in the maintenance of cancer stem cells with the SP phenotype in HCC cell lines. BMI1 was preferentially expressed in SP cells in Huh7 and PLC/PRF/5 HCC cells compared with the corresponding non-SP cells. Lentiviral knockdown of BMI1 considerably decreased the number of SP cells in both Huh7 and PLC/PRF/5 cells. Long-term culture of purified SP cells resulted in a drastic reduction in the SP subpopulation upon the BMI1 knockdown, indicating that BMI1 is required for the self-renewal of SP cells in culture. More importantly, the BMI1 knockdown abolished the tumor-initiating ability of SP cells in nonobese diabetic/severe combined immunodeficiency mice. Derepression of the INK4A and ARF genes that are major targets for BMI1 was not necessarily associated with impaired self-renewal of SP cells caused by BMI1 knockdown. In conclusion, our findings define an important role for BMI1 in the maintenance of tumor-initiating SP cells in HCC. BMI1 might be a novel therapeutic target for the eradication of cancer stem cells in HCC. [Cancer Res 2008;68(19):7742–9]
Data from Defective Claudin-7 Regulation by Tcf-4 and Sox-9 Disrupts the Polarity and Increases the Tumorigenicity of Colorectal Cancer Cells
Authors: Darido Charbel , Buchert Michael , Pannequin Julie , Bastide Pauline , Zalzali Hassan , Mantamadiotis Theo , Bourgaux Jean-François , Garambois Véronique , Jay Philippe , Blache Philippe , Joubert Dominique , Hollande Frédéric
Published: March 2023

Abstract
Tight junctions have recently emerged as essential signaling regulators of proliferation and differentiation in epithelial tissues. Here, we aimed to identify the factors regulating claudin-7 expression in the colon, and analyzed the consequences of claudin-7 overexpression in colorectal carcinoma (CRC). In healthy human colonic crypts, claudin-7 expression was found to be low in the stem/progenitor cell compartment, where Tcf-4 activity is high, but strong in differentiated and postmitotic cells, where Tcf-4 is inactive. In contrast, claudin-7 was overexpressed in areas with high Tcf-4 target gene levels in CRC samples. In vitro, Tcf-4 was able to repress claudin-7 expression, and the high mobility group–box transcription factor Sox-9 was identified as an essential mediator of this effect. Claudin-7 was strongly expressed in the intestine of Sox-9–deficient mice and in CRC cells with low Sox transcriptional activity. Sox-9 overexpression in these cells reinstated claudin-7 repression, and residual claudin-7 was no longer localized along the basolateral membrane, but was instead restricted to tight junctions. Using HT-29Cl.16E CRC cell spheroids, we found that Sox-9–induced polarization was completely reversed after virus-mediated claudin-7 overexpression. Claudin-7 overexpression in this context increased Tcf-4 target gene expression, proliferation, and tumorigenicity after injection in nude mice. Our results indicate that Tcf-4 maintains low levels of claudin-7 at the bottom of colonic crypts, acting via Sox-9. This negative regulation seems to be defective in CRC, possibly due to decreased Sox-9 activity, and the resulting claudin-7 overexpression promotes a loss of tumor cell polarization and contributes to tumorigenesis. [Cancer Res 2008;68(11):4258–68]
Data from Roles of Achaete-Scute Homologue 1 in DKK1 and E-cadherin Repression and Neuroendocrine Differentiation in Lung Cancer
Authors: Osada Hirotaka , Tomida Shuta , Yatabe Yasushi , Tatematsu Yoshio , Takeuchi Toshiyuki , Murakami Hideki , Kondo Yutaka , Sekido Yoshitaka , Takahashi Takashi
Published: March 2023

Abstract
The proneural basic-helix-loop-helix protein achaete-scute homologue 1 (ASH1) is expressed in a very limited spectrum of normal and cancerous cells in a lineage-specific manner, including normal pulmonary neuroendocrine cells and lung cancer cells with neuroendocrine features. Our previous results indicated that ASH1 may play a crucial role in the growth and survival of lung cancers with neuroendocrine features, which prompted us to investigate the molecular function of ASH1 in relation to its involvement in carcinogenic processes. Herein, we report for the first time that ASH1 functions as a dual transcription factor by activating neuroendocrine differentiation markers and also repressing putative tumor suppressors. This protein was found to inactivate DKK1 and DKK3, negative regulators of Wnt/β-catenin signaling, E-cadherin, and integrin β1 through ASH1-mediated deacetylation and repressive trimethylation of lysine 27 (H3K27me3) of histone H3 in the promoter regions of DKK1 and E-cadherin. In addition, ASH1-transduced A549 adenocarcinoma cells exhibited markedly altered morphology characteristics compared with lung cancer cells with neuroendocrine features both in vitro and in vivo and also grew faster in vivo. Our results provide important clues for a better understanding of the molecular and cellular biological roles of ASH1 in the process of carcinogenesis of lung cancers with neuroendocrine features and warrant future investigations to shed light on the lineage-specific dependency of this transcription factor with dual functions. [Cancer Res 2008;68(6):1647–55]
Data from Genome-Wide Copy Number Analysis in Esophageal Adenocarcinoma Using High-Density Single-Nucleotide Polymorphism Arrays
Authors: Nancarrow Derek J. , Handoko Herlina Y. , Smithers B. Mark , Gotley David C. , Drew Paul A. , Watson David I. , Clouston Andrew D. , Hayward Nicholas K. , Whiteman David C.
Published: March 2023

Abstract
We applied whole-genome single-nucleotide polymorphism arrays to define a comprehensive genetic profile of 23 esophageal adenocarcinoma (EAC) primary tumor biopsies based on loss of heterozygosity (LOH) and DNA copy number changes. Alterations were common, averaging 97 (range, 23–208) per tumor. LOH and gains averaged 33 (range, 3–83) and 31 (range, 11–73) per tumor, respectively. Copy neutral LOH events averaged 27 (range, 7–57) per EAC. We noted 126 homozygous deletions (HD) across the EAC panel (range, 0–11 in individual tumors). Frequent HDs within FHIT (17 of 23), WWOX (8 of 23), and DMD (6 of 23) suggest a role for common fragile sites or genomic instability in EAC etiology. HDs were also noted for known tumor suppressor genes (TSG), including CDKN2A, CDKN2B, SMAD4, and GALR1, and identified PDE4D and MGC48628 as potentially novel TSGs. All tumors showed LOH for most of chromosome 17p, suggesting that TSGs other than TP53 may be targeted. Frequent gains were noted around MYC (13 of 23), BCL9 (12 of 23), CTAGE1 (14 of 23), and ZNF217 (12 of 23). Thus, we have confirmed previous reports indicating frequent changes to FHIT, CDKN2A, TP53, and MYC in EAC and identified additional genes of interest. Meta-analysis of previous genome-wide EAC studies together with the data presented here highlighted consistent regions of gain on 8q, 18q, and 20q and multiple LOH regions on 4q, 5q, 17p, and 18q, suggesting that more than one gene may be targeted on each of these chromosome arms. The focal gains and deletions documented here are a step toward identifying the key genes involved in EAC development. [Cancer Res 2008;68(11):4163–72]
Data from A Retroinhibition Approach Reveals a Tumor Cell–Autonomous Response to Rapamycin in Head and Neck Cancer
Authors: Amornphimoltham Panomwat , Patel Vyomesh , Leelahavanichkul Kantima , Abraham Robert T. , Gutkind J. Silvio
Published: March 2023

Abstract
Emerging evidence supporting the activation of the Akt-mammalian target of rapamycin (mTOR) signaling network in head and neck squamous cell carcinoma (HNSCC) progression has provided the rationale for exploring the therapeutic potential of inhibiting this pathway for HNSCC treatment. Indeed, rapamycin, a clinically relevant mTOR inhibitor, promotes the rapid regression of HNSCC-tumor xenografts in mice. However, rapamycin does not affect the growth of HNSCC cells in vitro, thus raising the possibility that, as for other cancer types, rapamycin may not target cancer cells directly but may instead act on a component of the tumor microenvironment, such as tumor-associated vasculature. Here, we used a retroinhibition approach to assess the contribution of cancer cell–autonomous actions of rapamycin to its antitumor activity in HNSCC. A rapamycin-resistant form of mTOR (mTOR-RR) was expressed in HNSCC cells while retaining the wild-type (rapamycin-sensitive) mTOR (mTOR-WT) alleles in host-derived endothelial and stromal cells. Expression of mTOR-RR prevented the decrease in phospho-S6 levels caused by rapamycin through mTOR in HNSCC cells but not in stromal cells, and rendered HNSCC xenografts completely resistant to the antitumoral activity of rapamycin. This reverse pharmacology strategy also enabled monitoring the direct consequences of inhibiting mTOR in cancer cells within the complex tumor microenvironment, which revealed that mTOR controls the accumulation of hypoxia-inducible factor-1α (HIF-1α) and the consequent expression of vascular endothelial growth factor and a glucose transporter, Glut-1, in HNSCC cells. These findings indicate that HNSCC cells are the primary target of rapamycin in vivo, and provide evidence that its antiangiogenic effects may represent a downstream consequence of mTOR inhibition in HNSCC cells. [Cancer Res 2008;68(4):1144–53]
Data from Microphthalmia-Associated Transcription Factor Is a Critical Transcriptional Regulator of Melanoma Inhibitor of Apoptosis in Melanomas
Authors: Dynek Jasmin N. , Chan Sara M. , Liu Jinfeng , Zha Jiping , Fairbrother Wayne J. , Vucic Domagoj
Published: March 2023

Abstract
Melanoma inhibitor of apoptosis (ML-IAP) is a potent inhibitor of apoptosis, which is highly expressed in melanomas and likely contributes to their resistance to chemotherapeutic treatments. Herein, we show that the lineage survival oncogene microphthalmia-associated transcription factor (MITF) is a critical regulator of ML-IAP transcription in melanoma cells. The ML-IAP promoter contains two MITF consensus sites, and analysis of MITF and ML-IAP mRNA levels revealed a high correlation in melanoma tumor samples and cell lines. In reporter assays, MITF promoted a strong stimulation of transcriptional activity from the ML-IAP promoter, and MITF bound the endogenous ML-IAP promoter in melanoma cells by chromatin immunoprecipitation and electrophoretic mobility shift assay. Strikingly, small interfering RNA (siRNA)–mediated knockdown of MITF in melanoma cells led to a dramatic decrease in ML-IAP mRNA and protein levels, establishing that ML-IAP expression in melanoma cells is MITF dependent. Additionally, cyclic AMP–mediated induction of MITF expression in melanocytes resulted in increased ML-IAP expression, suggesting that melanocytes can express ML-IAP when MITF levels are heightened. Disruption of MITF by siRNA led to a decrease in melanoma cell viability, which could be rescued by ectopic expression of ML-IAP. Collectively, these findings implicate MITF as a major transcriptional regulator of ML-IAP expression in melanomas, and suggest that ML-IAP contributes to the prosurvival activity of MITF in melanoma progression. [Cancer Res 2008;68(9):3124–32]
Supplementary Table S2 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

MDSC Values by Vaccine Immune Response vs. Non-Response
Supplementary Methods S1 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

supplementary methods: trial administration
Supplementary Figure S4 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 4. Related to Fig. 2, 3 and Supplementary Fig. 5-7. 68-year-old female with bilateral lung metastases and multiple mediastinal lymph node metastasis was treated with chemo-immunotherapy (carboplatin, pemetrexed, and pembrolizumab). PD-L1 expression in the pre-treatment tumor specimen was 2%. The patient had stable disease for 621 days with overall survival > 3 years. A Contrast-enhanced cross-sectional imaging obtained at prior to and during treatment. B Expression of CX3CR1 in peripheral blood CD8 T cells (left) and the CX3CR1 score (right) at different time points as indicated.
Supplementary Fig. S3 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. S3 shows results of the "switching" therapy
Supplementary Figure S5 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

Measuring gene expression of F3 and PDPN after Wnt3a treatment of skin fibroblasts
Supplementary Figure S3 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

Type B (mutant) cells exhibit higher alpha-smooth muscle actin levels at the protein and RNA level.
Supplementary Figure S1 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

Decreasing mutational frequency with increasing passages in a desmoid tumor primary culture.
Data 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

Lack of reliable predictive biomarkers is a major limitation of combination therapy with chemotherapy and anti–programmed cell death protein 1/programmed death-ligand 1 (anti-PD-1/PD-L1) therapy (chemo-immunotherapy). We previously observed that the increase of peripheral blood CD8+ T cells expressing CX3CR1, a marker of differentiation, correlates with response to anti–PD-1 therapy; however, the predictive and prognostic value of T-cell CX3CR1 expression during chemo-immunotherapy is unknown. Here, we evaluated the utility of circulating CX3CR1+CD8+ T cells as a predictive correlate of response to chemo-immunotherapy in patients with non–small cell lung cancer (NSCLC). At least 10% increase of the CX3CR1+ subset in circulating CD8+ T cells from baseline (CX3CR1 score) was associated with response to chemo-immunotherapy as early as 4 weeks with 85.7% overall accuracy of predicting response at 6 weeks. Furthermore, at least 10% increase of the CX3CR1 score correlated with substantially better progression-free (P = 0.0051) and overall survival (P = 0.0138) on Kaplan–Meier analysis. Combined single-cell RNA/T-cell receptor (TCR) sequencing of circulating T cells from longitudinally obtained blood samples and TCR sequencing of tumor tissue from the same patient who received a long-term benefit from the treatment demonstrated remarkable changes in genomic and transcriptomic signatures of T cells as well as evolution of TCR clonotypes in peripheral blood containing highly frequent tumor-infiltrating lymphocyte repertoires overexpressing CX3CR1 early after initiation of the treatment despite stable findings of the imaging study. Collectively, these findings highlight the potential utility of T-cell CX3CR1 expression as a dynamic blood-based biomarker during the early course of chemo-immunotherapy and a marker to identify frequent circulating tumor-infiltrating lymphocyte repertoires.
Significance:
Current approaches to combined chemotherapy and anti-PD-1/PD-L1 therapy (chemo-immunotherapy) for patients with NSCLC are limited by the lack of reliable predictive biomarkers. This study shows the utility of T-cell differentiation marker, CX3CR1, as an early on-treatment predictor of response and changes in genomic/transcriptomic signatures of circulating tumor-infiltrating lymphocyte repertoires in patients with NSCLC undergoing chemo-immunotherapy.
First records of marine microturbellarians (Platyhelminthes: Rhabdocoela, Fecampiida and Prolecithophora) from Peru, with the description of a new species
Authors: VELÁSQUEZ-RODRIGUEZ KAREN , REYES JHOE , STEENKISTE NIELS VAN , SEVERINO RUPERTO , BRUSA FRANCISCO
Published: March 2023

The marine microturbellarian diversity is scarcely known from the Pacific coastline of South America. The coastal margin of Peru is highly influenced by cold-water currents (Humboldt Current System). These cold-water currents play important roles in shaping the marine species diversity in this area. However, there are no previous records of marine microturbellarians for Peru. Here, we describe a new species of Rhabdocoela and report on five other species of marine microturbellarians for this country. Carcharodorhynchus giaae n. sp. (Kalyptorhynchia, Schizorhynchidae), can be identified based on the configuration of the proboscis lips and the male and female genital systems. The male copulatory organ lacks a cirrus, but has a funnel-like, curved stylet with three pairs of spines along it, which distinguishes this species from its congeners. The female system has a vagina with a sclerotized, heavily coiled structure — a feature not mentioned in any known species of the same genus. In addition, we describe noteworthy features for another rhabdocoel, Trigonostomum galapagoense (Dalytyphloplanida, Trigonostomidae). Finally, we provide new records for three rhabdocoel species (Alcha evelinae, Itaipusa divae, Utelga heinckei), one species of Fecampiida (Urastoma cyprinae), and an unidentified species of Prolecithophora.
When the past meets the present: the oldest known Bibioninae, and the youngest known Cretobibioninae (Diptera, Bibionidae) from mid-Cretaceous Myanmar amber
Authors: SKARTVEIT JOHN
Published: March 2023

The Diptera family Bibionidae has a rich fossil record from the Tertiary, however little is known about this family in the Mesozoic. Recently, a number of specimens have been found in mid-Cretaceous Myanmar amber, dating from about 99 MYr BP. I report the finding of the oldest known member of the recent subfamily Bibioninae, as well as the youngest known member of the Cretaceous subfamily Cretobibioninae.The Cretobibioninae is represented by Cretobibio burmiticus sp. n., which suggests a wide, possibly cosmopolitan distribution of the recently discovered subfamily Cretobibionidae, the Bibioninae by Protodilophus semispinosus gen. et sp. n. The latter species is probably related to the recent and Tertiary genus Dilophus, but displays some plesiomorphic traits related to the more recent taxa.
60-year-old male with rapidly progressive pneumocephalus caused by Clostridium septicum in the setting of an occult colonic adenocarcinoma
Authors: Helmink Austin J. , Wahlig Taylor A. , Fey Paul D. , Chen Jie , Foster Kirk W.
Published: March 2023

Background

Disseminated Clostridium septicum infection is an uncommon complication associated with malignancies, particular colonic adenocarcinoma. The organism appears to preferentially colonize large masses in rare individuals and subsequently seed the blood via mucosal ulceration. This has rarely been reported to lead to central nervous system infection and, in several cases, rapidly progressive pneumocephalus. In the few cases reported, this was a universally fatal condition. The current case adds to the reports of this extremely rare complication and provides a unique and complete clinicopathologic characterization with autopsy examination, microscopy, and molecular testing.

Case Presentation

A 60-year-old man with no known past medical history was discovered having seizure-like activity and stroke-like symptoms. Blood cultures turned positive after six hours. Imaging revealed a large, irregular cecal mass as well as 1.4 cm collection of air in the left parietal lobe that progressed to over 7 cm within 8 h. By the following morning, the patient had lost all neurologic reflexes and died. Post-mortem examination revealed brain tissue with multiple grossly evident cystic spaces and intraparenchymal hemorrhage, while microscopic exam showed diffuse hypoxic-ischemic injury and gram-positive rods. Clostridium septicum was identified on blood cultures and was confirmed in paraffin embedded tissue from the brain by 16 S ribosomal sequencing and from the colon by C. septicum specific PCR.

Conclusions

C. septicum is an anaerobic, gram-positive rod that can become invasive and is strongly associated with gastrointestinal pathology including colonic adenocarcinomas. Central nervous system infection with rapidly progressive pneumocephalus is a rarely reported and universally fatal complication of disseminated C. septicum infection.
Acceptance of vaccination against pertussis, COVID-19 and influenza during pregnancy: a cross-sectional study
Authors: Widdershoven Veja , Reijs Rianne P. , Eskes Annika , Verhaegh-Haasnoot Amanja , Hoebe Christian J.P.A.
Published: March 2023

Background

This study aims to assess the uptake of maternal pertussis and COVID-19 vaccination and the intention towards accepting the maternal influenza vaccination. Insights into different socio-demographic factors related to maternal vaccination coverage might help to address vaccine acceptance and improve maternal vaccine uptake in the future.

Methods

We conducted a cross-sectional survey among pregnant women and recent mothers, up to 6 months post-partum. The primary outcome measures of this study were behaviour for maternal pertussis and COVID-19 vaccination, and maternal influenza vaccination intention. Associations between socio-demographic factors and maternal pertussis vaccination and maternal COVID-19 vaccination behaviour; and socio-demographic factors and maternal influenza vaccination intention were assessed using binary logistic regression analyses.

Results

In total 1361 respondents filled out the questionnaire. Almost all women (95%) were vaccinated against pertussis during pregnancy, while almost two-third were vaccinated against COVID-19 during pregnancy (58%) and almost one-third (28%) had a positive intention towards receiving the maternal influenza vaccination. Results show that young maternal age and low education level were associated with lower maternal vaccination acceptance.

Conclusion

Vaccination campaigns focusing on the severity of diseases that are prevented, are needed to increase maternal vaccine acceptance in younger and low-educated pregnant women. We expect that differences in vaccination coverage between the three maternal vaccinations might partly be explained by existing recommendations, campaigns and whether the vaccination is part of the national immunisation program.
Clinical efficacy and prognosis analysis of treatment regimens for EGFR mutant non-small cell lung cancer and brain metastasis: a retrospective study
Authors: Wang Huijuan , Xing Ruyue , Li Mengmeng , Zhang Mina , Wei Chunhua , Zhang Guowei , Niu Yuanyuan , Ma Zhiyong , Yan Xiangtao
Published: March 2023

Background

The aims of the study were to evaluate potential differences among first-line treatment for EGFR mutant (m+) non-small cell lung cancer (NSCLC) patients with brain metastasis in China and to identify the factors influencing survival outcomes.

Methods

In this retrospective study, 172 EGFRm + patients with advanced NSCLC who received a 1st generation EGFR tyrosine kinase inhibitor (TKI) were divided into 4 groups: A, EGFR-TKI (n = 84); B, EGFR-TKI + pemetrexed + cisplatin/carboplatin chemotherapy (CT) (n = 55); C, EGFR-TKI + bevacizumab (n = 15); and D, EGFR-TKI + pemetrexed + cisplatin/carboplatin CT + bevacizumab (n = 18). Intracranial and extracranial progression-free survival (PFS), the overall survival (OS), objective remission rates (ORRs) and adverse events were analyzed.

Results

Intracranial PFS of groups C + D was longer than for groups A + B (18.9 m vs. 11.0 m, P = 0.027). Extracranial PFS were longer in group B in comparison with group A (13.0 m vs. 11.5 m, P = 0.039) and in groups C + D compared to groups A + B (18.9 m vs. 11.9 m, P = 0.008). Median OS in groups A and B were 27.9 m and 24.4 m, respectively, while groups C and D have not yet achieved median OS. Significant difference was found in intracranial ORR between groups A + B vs. C + D (31.0% vs. 65.2%, P = 0.002). Most patients suffered grade 1–2 treatment-related adverse events, which were relieved soon after symptomatic treatment.

Conclusions

First-generation EGFR-TKI + bevacizumab treatment outperformed other regimens in EGFRm + NSCLC patients with brain metastasis. The therapy improved the control and delayed progression of intracranial lesions and prolonged survival times.
Giant pedunculated hepatoblastoma mimicking neuroblastoma in a 4-month-old infant: a case report
Authors: Zarei Elham , Vafadar Mehdi , Khonji Mohammad Saeid , Mounesi Sohi Amir Sajjad
Published: March 2023

Background

Hepatoblastoma is the most common primary malignancy of hepatic origin in children, with an estimated incidence of 0.5–1.5 per million children. Hepatoblastoma classically has an intraparenchymal location, and pedunculated hepatoblastoma is a relatively rare entity. Accurate diagnosis can be challenging due to its extrahepatic location and possibly its thin peduncle, which is not easily identified in imaging.

Case presentation

Here, we report a case of asymptomatic giant palpable hepatoblastoma in the LUQ of a four-month-old male infant, initially suspected of neuroblastoma based on abdominal ultrasound findings. The final diagnosis of giant pedunculated hepatoblastoma was made based on the abdominal CT scan and the diagnosis was confirmed by percutaneous biopsy. Due to the size of the tumor, complete removal of the tumor was not initially possible. Therefore, the patient was treated with several courses of chemotherapy. The tumor was shrunk and then completely removed. The patient was treated, and no complications were found in the 6-month follow-up.

Conclusion

Pedunculated hepatoblastoma is rare but should be considered as a possibility in the case of a perihepatic mass in a pediatric patient that can be confused with other upper abdominal masses such as an adrenal mass. Therefore, in such cases, we must look for the vascular pedicle in the imaging and keep the AFP check in mind.
Associations between body circumference and testosterone levels and risk of metabolic dysfunction-associated fatty liver disease: a mendelian randomization study
Authors: Ning Lin , Sun Jianguang
Published: March 2023

Backgroud

Body circumference and testosterone levels have been reported as associated with metabolic dysfunction-associated fatty liver disease (MAFLD) risk. However, whether body circumference and testosterone levels play a role in the development of MAFLD remains inconclusive.

Methods

Using a large database of genome-wide association studies, genetic loci that are independent of each other and strongly associated with body circumference and testosterone levels were selected as instrumental variables, the causal relationship between body circumference and testosterone and risk of MAFLD was investigated by two-sample Mendelian randomization methods such as inverse variance weighted (IVW), MR-Egger regression, and weighted median estimator (WME), using the odds ratios (ORs) as evaluation indicators.

Results

A total of 344 SNPs were included as instrumental variables in this study, including 180 for waist circumference, 29 for waist-to-hip ratio, and 135 for testosterone levels. Using the above two-sample Mendelian Randomization method to derive the causal association between exposure and outcome. The results of this study showed that three exposure factors were causally associated with the risk of MAFLD. Waist circumference obtained three statistically significant results for IVW, WME and Weighted mode (IVW: OR = 3.53, 95%CI: 2.23–5.57, P < 0.001; WME: OR = 3.88, 95%CI: 1.81–8.29, P < 0.001; Weighted mode: OR = 3.58, 95%CI: 1.05–12.16, P = 0.043). Waist-to-hip ratio obtained one statistically significant result for IVW (OR = 2.29, 95%CI: 1.12–4.66, P = 0.022). Testosterone levels obtained one statistically significant result for IVW (OR = 1.93, 95%CI: 1.30–2.87, P = 0.001). Waist circumference, waist-to-hip ratio and testosterone level were considered as risk factors for MAFLD. The Cochran Q test for IVW and MR-Egger method indicated that there was no intergenic heterogeneity in SNPs. The test for pleiotropy indicated that the possibility of pleiotropy in the causal analysis was weak.

Conclusion

The results of the two-sample Mendelian randomization analysis showed that waist circumference was the exact risk factor for MAFLD, waist-to-hip ratio and testosterone levels were potential risk factors for MAFLD, the risk of developing MAFLD increases with these three exposure factors.
One quick and simple fixation method: posterior malleolus fractures in spiral tibial fractures
Authors: Qi Hongfei , Li Zhong , Ma Teng , Ren Cheng , Xu Yibo , Huang Qiang , Feng Haoxuan , Zhang Kun , Lu Yao , Li Ming
Published: March 2023

Objective

Spiral fracture of tibia combined with posterior malleolar fracture (PMF) is a special and regular injury. There is no uniform fixation method for PMF in this kind of injury. Intramedullary nail is the first choice for the treatment of tibial spiral fracture. We proposed a minimally invasive percutaneous screw combined with intramedullary nail technology to fix the PMF in the tibial spiral fracture. This study aims to explore the effectiveness and advantages of this technology.

Materials and methods

From January 2017 to February 2020, 116 cases of spiral fracture of tibia combined with PMF who were operated in our hospital were divided into Fixation Group (FG) and No Fixation Group (NG) according to whether PMF was fixed. After minimally invasive percutaneous screw fixation of ankle fracture in FG patients, the tibial intramedullary nail was inserted to fix the fracture. Collected the operation and postoperative recovery of the two groups of patients, including the operation time, intraoperative blood loss, AOFAS score, VAS score and dorsiflexion restriction of ankle joint at the last follow-up, and compared whether there is any difference between the two groups of patients.

Results

The fracture of both groups healed.2 patients in NG had secondary displacement of PMF during operation, and the fracture finally healed after fixation. There were statistical differences between the two groups in terms of operation time, AOFAS score and weight bearing time. The operation time of FG was 67.9±11.2 min, and that of NG was 60.8±9.4 min; The weight bearing time of FG was 57.35±34.72 days, and that of NG was 69.17±21.43 days; The AOFAS score of FG was 92.50±3.46, and that of NG was 91.00±4.16. There were no significant difference in blood loss, VAS and dorsiflexion restriction of ankle joint between the two groups. The blood loss of FG was 66.8±12.3 ml, the blood loss of NG was 65.6±11.7 ml, the VAS score of FG was 1.37±0.47, the VAS score of NG was 1.43±0.51, the dorsiflexion restriction of FG was 5.8±4.1; the NG was 6.1±5.7.

Conclusion

For the injury of tibial spiral fracture combined with PMF, our fixation technology can achieve minimally invasive fixation of PMF with percutaneous screws on the basis of intramedullary nail fixation of tibial fracture, promoting early functional exercise of ankle joint and early weight bearing of patients. This fixation technology is also characterized by simple and fast operation.
Prevalence and associated factors of early sexual initiation among youth female in sub-Saharan Africa: a multilevel analysis of recent demographic and health surveys
Authors: Ferede Tigist Andargie , Muluneh Atalay Goshu , Wagnew Alemakef , Walle Agmasie Damtew
Published: March 2023

Background

Early sexual initiation is a major public health concern globally, specifically in Sub-Saharan African (SSA) countries where reproductive health care services are limited. It is strongly related to increased risk of HIV/AIDS, sexually transmitted diseases, unwanted pregnancy, adverse birth outcomes, and psychosocial problems. However, there is limited evidence on the prevalence and associated factors of early sexual initiation among youth females in SSA.

Methods

A secondary data analysis was employed based on the recent DHSs of sub-Saharan African countries. A total weighted sample of 184,942 youth females was considered for analysis. Given the hierarchical nature of DHS data, a multilevel binary logistic regression model was fitted. The Intra-class Correlation Coefficient (ICC), Median Odds Ratio (MOR), and Likelihood Ratio (LR) test were used to assess the presence of clustering. Four nested models were fitted and the model with the lowest deviance (-2LLR0 was selected as the best-fitted model. Variables with p-value < 0.2 in the bivariable multilevel binary logistic regression analysis were considered for the multivariable analysis. In the multivariable multilevel binary logistic regression analysis, the Adjusted Odds Ratio (AOR) with the 95% Confidence Interval (CI) was reported to declare the strength and statistical significance of the association.

Results

The prevalence of early sexual initiation among youth females in sub-Saharan Africa was 46.39% [95%CI: 41.23%, 51.5%] ranging from 16.66% in Rwanda to 71.70% in Liberia. In the final model, having primary level education [AOR = 0.82, 95% CI; 0.79, 0.85], and [AOR = 0.50, 95%CI; 0.48, 0.52], being rural [AOR = 1.05, 95%CI: 1.03, 1.07], having media exposure [AOR = 0.91, 95%CI: 0.89, 0.94], and belonged to a community with high media exposure [AOR = 0.92, 95%CI: 0.89,0.96] were found significantly associated with early sexual initiation.

Conclusion

The prevalence of early sexual initiation among youth females in SSA was high. Educational status, wealth index, residence, media exposure, and community media exposure have a significant association with early sexual initiation. These findings highlight those policymakers and other stakeholders had better give prior attention to empowering women, enhancing household wealth status, and media exposure to increase early sexual in the region.
Electronic platform-based education for radiology residents: results of a two-year survey
Authors: Quaia Emilio
Published: March 2023

Background

Electronic platform based-learning for residents is increasing. The aim of this study was to identify the most reliable predictor variables related to the usage of electronic platform-based educational material for radiology residents which can predict a successful multiple-choice test during the academic year.

Methods

A two year survey was conducted based on the records of electronic platform-based educational material for radiology residents. Radiology resident education was based on the educational content of two educational electronic platform databases named RADPrimer and STATdx (Elsevier, Amsterdam) consisting in evidence-based and expert-vetted summary information to support learning and diagnosing in radiology. A pool of multiple-choice questions was addressed in RADPrimer by each resident after 6 months from the beginning of each academic year, and at the end of the respective residency year as part of end of the year assessment. A per-resident analysis was performed to analyze the correlation between the amount of electronic platform content accessed by residents (measured by total login times, login frequency per month, and the number of per-topic addressed questions) in preparation for the electronic test during the academic year (predictor variables) and per-resident average percentage of correct answers on electronic test (outcome variable). Statistical significance (p < 0.05) was determined using logistic regression and correlation analysis.

Results

Total login times (OR, 3; 95% CI, 2.2 -4), login frequency per month (OR, 4; 95% CI, 3.1–5.3), the number of per-topic addressed questions (OR, 3; 95% CI, 2.2 -4), and the number of topic-verified correct answers to multiple choice test (OR, 30.5; 95% CI, 12.8–80.9) all showed a statistically significant correlation with final percentage of correct answers on final year electronic test.

Conclusion

The number of correct answers to multiple choice test was related to the number and frequency of login access, the number of per-topic addressed questions and the number of topic-verified correct answers to multiple choice test. The electronic-based educational material contributes significantly to a successful radiology residency program.
Menstrual health and hygiene among Juang women: a particularly vulnerable tribal group in Odisha, India
Authors: Mudi Prasanna Kumar , Pradhan Manas Ranjan , Meher Trupti
Published: March 2023

Background

Menstruation is a normal biological process that all women go through, yet it is shrouded in secrecy, taboos, and even stigma in many societies. Studies have shown that women from socially disadvantaged groups are more likely to have preventable reproductive health issues and have less understanding of hygienic menstrual practices. Therefore, this study aimed to provide an insight into the most sensitive issue of menstruation and menstrual hygiene practices among the women of the Juang tribe, recognized as one of the particularly vulnerable tribal groups (PVTG) in India.

Methods

A cross-sectional study using a mixed-method approach was carried out among Juang women in Keonjhar district of Odisha, India. Quantitative data was gathered from 360 currently married women to assess practices associated with menstruation and its management. In addition, 15 focus group discussions and 15 in-depth interviews were conducted to explore the views of Juang women on menstrual hygiene practices, cultural beliefs, menstrual problems, and treatment-seeking behaviour. Inductive content analysis was used to analyse the qualitative data, while descriptive statistics and chi-squared tests were used to analyse quantitative data.

Results

Most Juang women (85%) used old clothes as absorbents during menstruation. Distance from the market (36%), lack of awareness (31%), and high cost (15%) were cited as the contributing factors to the low level of sanitary napkin usage. Around 85% of women were restricted from participating in religious activities, and 94% avoided social gatherings. Seventy-one percent of the Juang women experienced menstrual problems, while only one-third of them sought treatment for their problems.

Conclusion

Hygienic practices during menstruation are far from satisfactory among Juang women in Odisha, India. Menstrual problems are common, and the treatment sought is insufficient. There is a need for awareness generation on menstrual hygiene, the adverse effects of menstrual problems, and the provision of low-cost sanitary napkins among this disadvantaged, vulnerable tribal group.