bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Identification of Novel Therapeutic Targets for Fibrolamellar Carcinoma Using Patient-Derived Xenografts and Direct-from-Patient Screening
Authors: Lalazar Gadi , Requena David , Ramos-Espiritu Lavoisier , Ng Denise , Bhola Patrick D. , de Jong Ype P. , Wang Ruisi , Narayan Nicole J.C. , Shebl Bassem , Levin Solomon , Michailidis Eleftherios , Kabbani Mohammad , Vercauteren Koen O.A. , Hurley Arlene M. , Farber Benjamin A. , Hammond William J. , Saltsman James A. , Weinberg Ethan M. , Glickman J. Fraser , Lyons Barbara A. , Ellison Jessica , Schadde Erik , Hertl Martin , Leiting Jennifer L. , Truty Mark J. , Smoot Rory L. , Tierney Faith , Kato Tomoaki , Wendel Hans-Guido , LaQuaglia Michael P. , Rice Charles M. , Letai Anthony , Coffino Philip , Torbenson Michael S. , Ortiz Michael V. , Simon Sanford M.
Published: March 2024

Abstract
To repurpose therapeutics for fibrolamellar carcinoma (FLC), we developed and validated patient-derived xenografts (PDX) from surgical resections. Most agents used clinically and inhibitors of oncogenes overexpressed in FLC showed little efficacy on PDX. A high-throughput functional drug screen found primary and metastatic FLC were vulnerable to clinically available inhibitors of TOPO1 and HDAC and to napabucasin. Napabucasin's efficacy was mediated through reactive oxygen species and inhibition of translation initiation, and specific inhibition of eIF4A was effective. The sensitivity of each PDX line inversely correlated with expression of the antiapoptotic protein Bcl-xL, and inhibition of Bcl-xL synergized with other drugs. Screening directly on cells dissociated from patient resections validated these results. This demonstrates that a direct functional screen on patient tumors provides therapeutically informative data within a clinically useful time frame. Identifying these novel therapeutic targets and combination therapies is an urgent need, as effective therapeutics for FLC are currently unavailable.
Significance:
Therapeutics informed by genomics have not yielded effective therapies for FLC. A functional screen identified TOPO1, HDAC inhibitors, and napabucasin as efficacious and synergistic with inhibition of Bcl-xL. Validation on cells dissociated directly from patient tumors demonstrates the ability for functional precision medicine in a solid tumor.

This article is highlighted in the In This Issue feature, p. 2355
Data from Integrated Genomic Analysis Identifies Driver Genes and Cisplatin-Resistant Progenitor Phenotype in Pediatric Liver Cancer
Authors: Hirsch Theo Z. , Pilet Jill , Morcrette Guillaume , Roehrig Amélie , Monteiro Benedict J.E. , Molina Laura , Bayard Quentin , Trépo Eric , Meunier Léa , Caruso Stefano , Renault Victor , Deleuze Jean-François , Fresneau Brice , Chardot Christophe , Gonzales Emmanuel , Jacquemin Emmanuel , Guerin Florent , Fabre Monique , Aerts Isabelle , Taque Sophie , Laithier Véronique , Branchereau Sophie , Guettier Catherine , Brugières Laurence , Rebouissou Sandra , Letouzé Eric , Zucman-Rossi Jessica
Published: March 2024

Abstract
Pediatric liver cancers (PLC) comprise diverse diseases affecting infants, children, and adolescents. Despite overall good prognosis, PLCs display heterogeneous response to chemotherapy. Integrated genomic analysis of 126 pediatric liver tumors showed a continuum of driver mechanisms associated with patient age, including new targetable oncogenes. In 10% of patients with hepatoblastoma, all before three years old, we identified a mosaic premalignant clonal expansion of cells altered at the 11p15.5 locus. Analysis of spatial and longitudinal heterogeneity revealed an important plasticity between “hepatocytic,” “liver progenitor,” and “mesenchymal” molecular subgroups of hepatoblastoma. We showed that during chemotherapy, “liver progenitor” cells accumulated massive loads of cisplatin-induced mutations with a specific mutational signature, leading to the development of heavily mutated relapses and metastases. Drug screening in PLC cell lines identified promising targets for cisplatin-resistant progenitor cells, validated in mouse xenograft experiments. These data provide new insights into cisplatin resistance mechanisms in PLC and suggest alternative therapies.
Significance:
PLCs are deadly when they resist chemotherapy, with limited alternative treatment options. Using a multiomics approach, we identified PLC driver genes and the cellular phenotype at the origin of cisplatin resistance. We validated new treatments targeting these molecular features in cell lines and xenografts.

This article is highlighted in the In This Issue feature, p. 2355
Data from Reducing Skin Toxicities from EGFR Inhibitors with Topical BRAF Inhibitor Therapy
Authors: Lacouture Mario E. , Wainberg Zev A. , Patel Anisha B. , Anadkat Milan J. , Stemmer Salomon M. , Shacham-Shmueli Einat , Medina Egmidio , Zelinger Galit , Shelach Noa , Ribas Antoni
Published: March 2024

Abstract
Treatment of cancer with EGFR inhibitors is limited by on-target skin toxicities induced by inhibition of the MAPK pathway. BRAF inhibitors are known to paradoxically activate the MAPK downstream of EGFR, which we confirmed using human skin keratinocytes. We then conducted a phase I clinical trial testing the hypothesis that topical therapy with the BRAF inhibitor LUT014 could improve skin toxicities induced by EGFR inhibitors. Ten patients with metastatic colorectal cancer who had developed acneiform rash while being treated with cetuximab or panitumumab were enrolled in three cohorts. LUT014 was well tolerated, and there were no dose-limiting toxicities. The acneiform rash improved in the 6 patients who started with grade 2 rash in the low and intermediate cohorts. We conclude that topical LUT014 is safe and efficacious in improving rash from EGFR inhibitors, consistent with the mechanism of action inducting paradoxical MAPK activation.
Significance:
BRAF inhibitor topical therapy could avoid dose reductions of EGFR inhibitors, locally treating the main dose-limiting skin toxicity of this class of agents.

This article is highlighted in the In This Issue feature, p. 2113
Data from Overcoming Resistance to Tumor-Targeted and Immune-Targeted Therapies
Authors: Aldea Mihaela , Andre Fabrice , Marabelle Aurelien , Dogan Semih , Barlesi Fabrice , Soria Jean-Charles
Published: March 2024

Abstract
Resistance to anticancer therapies includes primary resistance, usually related to lack of target dependency or presence of additional targets, and secondary resistance, mostly driven by adaptation of the cancer cell to the selection pressure of treatment. Resistance to targeted therapy is frequently acquired, driven by on-target, bypass alterations, or cellular plasticity. Resistance to immunotherapy is often primary, orchestrated by sophisticated tumor–host–microenvironment interactions, but could also occur after initial efficacy, mostly when only partial responses are obtained. Here, we provide an overview of resistance to tumor and immune-targeted therapies and discuss challenges of overcoming resistance, and current and future directions of development.
Significance:
A better and earlier identification of cancer-resistance mechanisms could avoid the use of ineffective drugs in patients not responding to therapy and provide the rationale for the administration of personalized drug associations. A clear description of the molecular interplayers is a prerequisite to the development of novel and dedicated anticancer drugs. Finally, the implementation of such cancer molecular and immunologic explorations in prospective clinical trials could de-risk the demonstration of more effective anticancer strategies in randomized registration trials, and bring us closer to the promise of cure.
Data from Anti-Inflammatory Drugs Remodel the Tumor Immune Environment to Enhance Immune Checkpoint Blockade Efficacy
Authors: Pelly Victoria S. , Moeini Agrin , Roelofsen Lisanne M. , Bonavita Eduardo , Bell Charlotte R. , Hutton Colin , Blanco-Gomez Adrian , Banyard Antonia , Bromley Christian P. , Flanagan Eimear , Chiang Shih-Chieh , Jørgensen Claus , Schumacher Ton N. , Thommen Daniela S. , Zelenay Santiago
Published: March 2024

Abstract
Identifying strategies to improve the efficacy of immune checkpoint blockade (ICB) remains a major clinical need. Here, we show that therapeutically targeting the COX2/PGE2/EP2-4 pathway with widely used nonsteroidal and steroidal anti-inflammatory drugs synergized with ICB in mouse cancer models. We exploited a bilateral surgery model to distinguish responders from nonresponders shortly after treatment and identified acute IFNγ-driven transcriptional remodeling in responder mice, which was also associated with patient benefit to ICB. Monotherapy with COX2 inhibitors or EP2-4 PGE2 receptor antagonists rapidly induced this response program and, in combination with ICB, increased the intratumoral accumulation of effector T cells. Treatment of patient-derived tumor fragments from multiple cancer types revealed a similar shift in the tumor inflammatory environment to favor T-cell activation. Our findings establish the COX2/PGE2/EP2-4 axis as an independent immune checkpoint and a readily translatable strategy to rapidly switch the tumor inflammatory profile from cold to hot.
Significance:
Through performing in-depth profiling of mice and human tumors, this study identifies mechanisms by which anti-inflammatory drugs rapidly alter the tumor immune landscape to enhance tumor immunogenicity and responses to immune checkpoint inhibitors.

See related commentary by Melero et al., p. 2372.

This article is highlighted in the In This Issue feature, p. 2355
Data from Resolving the Spatial and Cellular Architecture of Lung Adenocarcinoma by Multiregion Single-Cell Sequencing
Authors: Sinjab Ansam , Han Guangchun , Treekitkarnmongkol Warapen , Hara Kieko , Brennan Patrick M. , Dang Minghao , Hao Dapeng , Wang Ruiping , Dai Enyu , Dejima Hitoshi , Zhang Jiexin , Bogatenkova Elena , Sanchez-Espiridion Beatriz , Chang Kyle , Little Danielle R. , Bazzi Samer , Tran Linh M. , Krysan Kostyantyn , Behrens Carmen , Duose Dzifa Y. , Parra Edwin R. , Raso Maria Gabriela , Solis Luisa M. , Fukuoka Junya , Zhang Jianjun , Sepesi Boris , Cascone Tina , Byers Lauren Averett , Gibbons Don L. , Chen Jichao , Moghaddam Seyed Javad , Ostrin Edwin J. , Rosen Daniel , Heymach John V. , Scheet Paul , Dubinett Steven M. , Fujimoto Junya , Wistuba Ignacio I. , Stevenson Christopher S. , Spira Avrum , Wang Linghua , Kadara Humam
Published: March 2024

Abstract
Little is known of the geospatial architecture of individual cell populations in lung adenocarcinoma (LUAD) evolution. Here, we perform single-cell RNA sequencing of 186,916 cells from five early-stage LUADs and 14 multiregion normal lung tissues of defined spatial proximities from the tumors. We show that cellular lineages, states, and transcriptomic features geospatially evolve across normal regions to LUADs. LUADs also exhibit pronounced intratumor cell heterogeneity within single sites and transcriptional lineage-plasticity programs. T regulatory cell phenotypes are increased in normal tissues with proximity to LUAD, in contrast to diminished signatures and fractions of cytotoxic CD8+ T cells, antigen-presenting macrophages, and inflammatory dendritic cells. We further find that the LUAD ligand–receptor interactome harbors increased expression of epithelial CD24, which mediates protumor phenotypes. These data provide a spatial atlas of LUAD evolution, and a resource for identification of targets for its treatment.
Significance:
The geospatial ecosystem of the peripheral lung and early-stage LUAD is not known. Our multiregion single-cell sequencing analyses unravel cell populations, states, and phenotypes in the spatial and ecologic evolution of LUAD from the lung that comprise high-potential targets for early interception.

This article is highlighted in the In This Issue feature, p. 2355
Data from TLR7 Ligand Augments GM-CSF–Initiated Antitumor Immunity through Activation of Plasmacytoid Dendritic Cells
Authors: Narusawa Megumi , Inoue Hiroyuki , Sakamoto Chika , Matsumura Yumiko , Takahashi Atsushi , Inoue Tomoko , Watanabe Ayumi , Miyamoto Shohei , Miura Yoshie , Hijikata Yasuki , Tanaka Yoshihiro , Inoue Makoto , Takayama Koichi , Okazaki Toshihiko , Hasegawa Mamoru , Nakanishi Yoichi , Tani Kenzaburo
Published: March 2024

Abstract
Vaccination with irradiated granulocyte macrophage colony-stimulating factor (GM-CSF)–transduced autologous tumor cells (GVAX) has been shown to induce therapeutic antitumor immunity. However, its effectiveness is limited. We therefore attempted to improve the antitumor effect by identifying little-known key pathways in GM-CSF–sensitized dendritic cells (GM-DC) in tumor-draining lymph nodes (TDLN). We initially confirmed that syngeneic mice subcutaneously injected with poorly immunogenic Lewis lung carcinoma (LLC) cells transduced with Sendai virus encoding GM-CSF (LLC/SeV/GM) remarkably rejected the tumor growth. Using cDNA microarrays, we found that expression levels of type I interferon (IFN)–related genes, predominantly expressed in plasmacytoid DCs (pDC), were significantly upregulated in TDLN-derived GM-DCs and focused on pDCs. Indeed, mouse experiments demonstrated that the effective induction of GM-CSF–induced antitumor immunity observed in immunocompetent mice treated with LLC/SeV/GM cells was significantly attenuated when pDC-depleted or IFNα receptor knockout (IFNAR−/−) mice were used. Importantly, in both LLC and CT26 colon cancer–bearing mice, the combinational use of imiquimod with autologous GVAX therapy overcame the refractoriness to GVAX monotherapy accompanied by tolerability. Mechanistically, mice treated with the combined vaccination displayed increased expression levels of CD86, CD9, and Siglec-H, which correlate with an antitumor phenotype, in pDCs, but decreased the ratio of CD4+CD25+FoxP3+ regulatory T cells in TDLNs. Collectively, these findings indicate that the additional use of imiquimod to activate pDCs with type I IFN production, as a positive regulator of T-cell priming, could enhance the immunologic antitumor effects of GVAX therapy, shedding promising light on the understanding and treatment of GM-CSF–based cancer immunotherapy. Cancer Immunol Res; 2(6); 568–80. ©2014 AACR.
Data from Tumor MHC Class I Expression Improves the Prognostic Value of T-cell Density in Resected Colorectal Liver Metastases
Authors: Turcotte Simon , Katz Steven C. , Shia Jinru , Jarnagin William R. , Kingham T. Peter , Allen Peter J. , Fong Yuman , D'Angelica Michael I. , DeMatteo Ronald P.
Published: March 2024

Abstract
Tumor-infiltrating lymphocytes (TIL) in colorectal cancer liver metastases (CLM) have been associated with more favorable patient outcomes, but whether MHC class I (MHC-I) expression on cancer cells affects prognosis is uncertain. Immunohistochemistry was performed on a tissue microarray of 158 patients with CLM, who underwent partial hepatectomy with curative intent. Using the antibody HC-10, which detects HLA-B and HLA-C antigens and a minority of HLA-A antigens, MHC-I expression was correlated with β-2 microglobulin (β2m; r = 0.7; P < 0.001), but not with T-cell density (r < 0.32). The median follow-up for survivors was 9.7 years. High levels of MHC-I expression in tumors concomitant with high T-cell infiltration (CD3, CD4, or CD8) best identified patients with favorable outcomes, compared with patients with one or none of these immune features. The median overall survival (OS) of patients with MHC-IhiCD3hi tumors (n = 31) was 116 months compared with 40 months for the others (P = 0.001), and the median time to recurrence (TTR) was not reached compared with 17 months (P = 0.008). By multivariate analysis, MHChiCD3hi was associated with OS and TTR independent of the standard clinicopathologic variables. An immune score that combines MHC-I expression and TIL density may be a valuable prognostic tool in the treatment of patients with CLM. Cancer Immunol Res; 2(6); 530–7. ©2014 AACR.
Data from Mast Cells Boost Myeloid-Derived Suppressor Cell Activity and Contribute to the Development of Tumor-Favoring Microenvironment
Authors: Danelli Luca , Frossi Barbara , Gri Giorgia , Mion Francesca , Guarnotta Carla , Bongiovanni Lucia , Tripodo Claudio , Mariuzzi Laura , Marzinotto Stefania , Rigoni Alice , Blank Ulrich , Colombo Mario P. , Pucillo Carlo E.
Published: March 2024

Abstract
Inflammation plays crucial roles at different stages of tumor development and may lead to the failure of immune surveillance and immunotherapy. Myeloid-derived suppressor cells (MDSC) are one of the major components of the immune-suppressive network that favors tumor growth, and their interaction with mast cells is emerging as critical for the outcome of the tumor-associated immune response. Herein, we showed the occurrence of cell-to-cell interactions between MDSCs and mast cells in the mucosa of patients with colon carcinoma and in the colon and spleen of tumor-bearing mice. Furthermore, we demonstrated that the CT-26 colon cancer cells induced the accumulation of CD11b+Gr1+ immature MDSCs and the recruitment of protumoral mast cells at the tumor site. Using ex vivo analyses, we showed that mast cells have the ability to increase the suppressive properties of spleen-derived monocytic MDSCs, through a mechanism involving IFNγ and nitric oxide production. In addition, we demonstrated that the CD40:CD40L cross-talk between the two cell populations is responsible for the instauration of a proinflammatory microenvironment and for the increase in the production of mediators that can further support MDSC mobilization and tumor growth. In light of these results, interfering with the MDSC:mast cell axis could be a promising approach to abrogate MDSC-related immune suppression and to improve the antitumor immune response. Cancer Immunol Res; 3(1); 85–95. ©2014 AACR.
Data from Autophagy Inhibition Dysregulates TBK1 Signaling and Promotes Pancreatic Inflammation
Authors: Yang Shenghong , Imamura Yu , Jenkins Russell W. , Cañadas Israel , Kitajima Shunsuke , Aref Amir , Brannon Arthur , Oki Eiji , Castoreno Adam , Zhu Zehua , Thai Tran , Reibel Jacob , Qian Zhirong , Ogino Shuji , Wong Kwok K. , Baba Hideo , Kimmelman Alec C. , Pasca Di Magliano Marina , Barbie David A.
Published: March 2024

Abstract
Autophagy promotes tumor progression downstream of oncogenic KRAS, yet also restrains inflammation and dysplasia through mechanisms that remain incompletely characterized. Understanding the basis of this paradox has important implications for the optimal targeting of autophagy in cancer. Using a mouse model of cerulein-induced pancreatitis, we found that loss of autophagy by deletion of Atg5 enhanced activation of the IκB kinase (IKK)-related kinase TBK1 in vivo, associated with increased neutrophil and T-cell infiltration and PD-L1 upregulation. Consistent with this observation, pharmacologic or genetic inhibition of autophagy in pancreatic ductal adenocarcinoma cells, including suppression of the autophagy receptors NDP52 or p62, prolonged TBK1 activation and increased expression of CCL5, IL6, and several other T-cell and neutrophil chemotactic cytokines in vitro. Defective autophagy also promoted PD-L1 upregulation, which is particularly pronounced downstream of IFNγ signaling and involves JAK pathway activation. Treatment with the TBK1/IKKϵ/JAK inhibitor CYT387 (also known as momelotinib) not only inhibits autophagy, but also suppresses this feedback inflammation and reduces PD-L1 expression, limiting KRAS-driven pancreatic dysplasia. These findings could contribute to the dual role of autophagy in oncogenesis and have important consequences for its therapeutic targeting. Cancer Immunol Res; 4(6); 520–30. ©2016 AACR.
Data from IFNγ-Dependent Interactions between ICAM-1 and LFA-1 Counteract Prostaglandin E2–Mediated Inhibition of Antitumor CTL Responses
Authors: Basingab Fatemah Salem , Ahmadi Maryam , Morgan David John
Published: March 2024

Abstract
Tumor-expressed ICAM-1 interaction with LFA-1 on naïve tumor-specific CD8+ T cells not only stabilizes adhesion, but, in the absence of classical B7-mediated costimulation, is also able to provide potent alternative costimulatory signaling resulting in the production of antitumor cytotoxic T lymphocyte (CTL) responses. This study shows that overproduction of prostaglandin (PG) E2 by metastatic murine renal carcinoma (Renca) cells inhibited direct priming of tumor-specific CTL responses in vivo by preventing the IFNγ-dependent upregulation of ICAM-1 that is vital during the initial priming of naïve CD8+ T cells. The addition of exogenous IFNγ during naïve CD8+ T-cell priming abrogated PGE2-mediated suppression, and overexpression of ICAM-1 by tumor cells restored IFNγ production and proliferation among PGE2-treated tumor-specific CD8+ T cells; preventing tumor growth in vivo. These findings suggest that novel anticancer immunotherapies, which increase expression of ICAM-1 on tumor cells, could help alleviate PGE2-mediated immunosuppression of antitumor CTL responses. Cancer Immunol Res; 4(5); 400–11. ©2016 AACR.
Data from IL15 Infusion of Cancer Patients Expands the Subpopulation of Cytotoxic CD56bright NK Cells and Increases NK-Cell Cytokine Release Capabilities
Authors: Dubois Sigrid , Conlon Kevin C. , Müller Jürgen R. , Hsu-Albert Jennifer , Beltran Nancy , Bryant Bonita R. , Waldmann Thomas A.
Published: March 2024

Abstract
The cytokine IL15 is required for survival and activation of natural killer (NK) cells as well as expansion of NK-cell populations. Here, we compare the effects of continuous IL15 infusions on NK-cell subpopulations in cancer patients. Infusions affected the CD56bright NK-cell subpopulation in that the expansion rates exceeded those of CD56dim NK-cell populations with a 350-fold increase in their total cell numbers compared with 20-fold expansion for the CD56dim subset. CD56bright NK cells responded with increased cytokine release to various stimuli, as expected given their immunoregulatory functions. Moreover, CD56bright NK cells gained the ability to kill various target cells at levels that are typical for CD56dim NK cells. Some increased cytotoxic activities were also observed for CD56dim NK cells. IL15 infusions induced expression changes on the surface of both NK-cell subsets, resulting in a previously undescribed and similar phenotype. These data suggest that IL15 infusions expand and arm CD56bright NK cells that alone or in combination with tumor-targeting antibodies may be useful in the treatment of cancer. Cancer Immunol Res; 5(10); 929–38. ©2017 AACR.
Data from Reversal of NK-Cell Exhaustion in Advanced Melanoma by Tim-3 Blockade
Authors: da Silva Ines Pires , Gallois Anne , Jimenez-Baranda Sonia , Khan Shaukat , Anderson Ana C. , Kuchroo Vijay K. , Osman Iman , Bhardwaj Nina
Published: March 2024

Abstract
The immunoregulatory protein T-cell immunoglobulin- and mucin-domain–containing molecule-3 (Tim-3) mediates T-cell exhaustion and contributes to the suppression of immune responses in both viral infections and tumors. Tim-3 blockade reverses the exhausted phenotype of CD4+ and CD8+ T cells in several chronic diseases, including melanoma. Interestingly, natural killer (NK) cells constitutively express Tim-3; however, the role of Tim-3 in modulating the function of these innate effector cells remains unclear, particularly in human diseases. In this study, we compared the function of Tim-3 in NK cells from healthy donors and patients with metastatic melanoma. NK cells from the latter were functionally impaired/exhausted, and Tim-3 blockade reversed this exhausted phenotype. Moreover, Tim-3 expression levels were correlated with the stage of the disease and poor prognostic factors. These data indicate that Tim-3 can function as an NK-cell exhaustion marker in advanced melanoma and support the development of Tim-3–targeted therapies to restore antitumor immunity. Cancer Immunol Res; 2(5); 410–22. ©2014 AACR.
New species, new synonymy, taxonomic notes and new records of bark and ambrosia beetles from the southwestern United States and northern Mexico (Coleoptera: Curculionidae: Platypodinae and Scolytinae)
Authors: ATKINSON THOMAS H.
Published: March 2024

Chaetophloeus flourensiae new species, is described from the Chihuahuan Desert from Arizona and western Texas and Hylocurus incognitus new species is described from Texas, Oklahoma and Louisiana. New synonymies include: Chramesus mimosae Blackman, 1938 (= Chramesus varius Wood, 1969); Hylocurus rudis (LeConte, 1876) (= Hylocurus binodatus Wood, 1974; Hypothenemus seriatus (Eichhoff, 1872) (= Stephanoderes multidentatus Hopkins, 1915, Stephanoderes nitidifrons Hopkins, 1915, Hypothenemus hopkinsi Browne, 1963); Hypothenemus pubescens Hopkins, 1915 (= Hypothenemus sparsus Hopkins, 1915, Hypothenenus similis Hopkins, 1915, Stephanoderes tridentatus Hopkins, 1915); Phloeotribus scabricollis Hopkins, 1916 (=Phloeotribus pseudoscabricollis Atkinson, 1989; Pseudothysanoes yuccae (Wood, 1956), (=Pseudothysanoes yuccavorus Wood, 1971); and Thysanoes texanus Blackman, 1943 (=Thysanoes mexicanus Wood, 1956). Hylocurus schwarzi Blackman, 1928, is redescribed including the first description of the female. New locality and host records that significantly extend the respective ranges are included for 30 species from the border region of the United States and Mexico.
Contributions to Odontogryllini (Orthoptera: Gryllidae: Landrevinae) with comments on its taxonomic status and description of a new species of Xulavuna de Mello & Campos, 2014
Authors: OYA BEATRIZ HARUMI KONDO , SANTOS LUIZ AUGUSTO PADILHA , FERNANDES JOSÉ ANTÔNIO MARIN , TAVARES GUSTAVO COSTA
Published: March 2024

Odontogryllini is a tribe of ground-dwelling crickets exclusive to America. After several taxonomic rearrangements, this tribe has five genera and 23 species now placed in the subfamily Landrevinae. These crickets have dorsoventrally depressed bodies and are moderately to densely covered with bristles. The males may bear tegminal, metanotal, or tergal glands. In this contribution, we discuss the taxonomic status and the morphological features of Odontogryllini and the other two tribes of Landrevinae: Landrevini and Prolandrevini. The presence of dorsal spines between the outer spurs of the hind tibia distinguishes Odontogryllini from Prolandrevini, and the straight or slightly arcuate but never S-shaped stridulum from Landrevini. We also propose the enlarged and plate-like rami as a diagnostic characteristic to distinguish Odontogryllini from Landrevini. Additionally, we describe a new species of the genus Xulavuna de Mello & Campos from the Brazilian Amazon Rainforest, named Xulavuna krenakore sp. nov..
Machine learning on alignment features for parent-of-origin classification of simulated hybrid RNA-seq
Authors: Miller Jason R. , Adjeroh Donald A.
Published: March 2024

Background

Parent-of-origin allele-specific gene expression (ASE) can be detected in interspecies hybrids by virtue of RNA sequence variants between the parental haplotypes. ASE is detectable by differential expression analysis (DEA) applied to the counts of RNA-seq read pairs aligned to parental references, but aligners do not always choose the correct parental reference.

Results

We used public data for species that are known to hybridize. We measured our ability to assign RNA-seq read pairs to their proper transcriptome or genome references. We tested software packages that assign each read pair to a reference position and found that they often favored the incorrect species reference. To address this problem, we introduce a post process that extracts alignment features and trains a random forest classifier to choose the better alignment. On each simulated hybrid dataset tested, our machine-learning post-processor achieved higher accuracy than the aligner by itself at choosing the correct parent-of-origin per RNA-seq read pair.

Conclusions

For the parent-of-origin classification of RNA-seq, machine learning can improve the accuracy of alignment-based methods. This approach could be useful for enhancing ASE detection in interspecies hybrids, though RNA-seq from real hybrids may present challenges not captured by our simulations. We believe this is the first application of machine learning to this problem domain.
Innovative cardiovascular casting technique features the complex malformation of berry syndrome
Authors: Li Wei , Feng Wei , Chang Caihong , Liu Ya , Li Xue , Wang Mofeng , Gan Ling , Zhang Jiaqi
Published: March 2024

Background

Prenatal diagnosis of Berry syndrome, a rare combination of cardiac anomalies including aortopulmonary window (APW), aortic origin of the right pulmonary artery (RPA), interrupted aortic arch (IAA), hypoplastic aortic arch, or coarctation of the aorta (COA), poses a significant challenge. Due to the rarity of the disease, and the limited case reports available to features the complex malformation of Berry syndrome postpartum, this article introduces an innovative approach to visually showcase this unusual disease. The proposed method provides a comprehensive display of the structural deformities, offering valuable insights for clinical practitioners seeking to comprehend this condition.

Case presentation

In this report, we present a case where fetal echocardiography aided in diagnosing Berry syndrome, which was later confirmed through postpartum cardiovascular casting. Our experience highlights the importance of using the three-vessel view to diagnose APW and aortic origin of the right pulmonary artery. Additionally, obtaining true cross-sectional and sagittal views by continuously scanning from the three-vessel-trachea view to the long-axis view of the aortic arch is necessary to image IAA or coarctation of the aortic arch.

Conclusions

Early and accurate prenatal diagnosis of Berry syndrome is feasible and our cardiovascular cast can perfectly display the microvascular morphology of the fetal heart, which may have great application prospects for postpartum diagnosis and teaching of complex cardiac abnormalities.
Effect of a chimney-fitted improved stove on pregnancy outcomes in Northwest Ethiopia: a randomized controlled trial
Authors: Enyew Habtamu Demelash , Hailu Abebe Beyene , Mereta Seid Tiku
Published: March 2024

Background

Exposure to household air pollution during pregnancy has been linked to adverse pregnancy outcomes. Improved stove was implemented in Ethiopia to reduce this exposure and related health problems. However, the effects of improved stove interventions on pregnancy outcomes remains uncertain.

Method

Individually randomized stove replacement trial was conducted among 422 households in six low-income rural kebeles of Northwestern Ethiopia. Pregnant women without known health conditions were recruited at ≤ 24 weeks gestation and randomized to an intervention or control group with a 1:1 ratio. A baseline survey was collected and a balance test was done. Two-sided independent samples t-test for continuous outcomes and chi-square for categorical variables were used to compare the effect of the intervention between the groups. Mean differences with 95% CIs were calculated and a p-value of < 0.05 was considered statistically significant.

Result

In this study, the mean birth weight was 3065 g (SD = 453) among the intervention group and not statistically different from 2995 g (SD = 541) of control group. After adjusting for covariates, infants born from intervention group weighed 55 g more [95% CI: − 43 to 170) than infants born from the control group, but the difference was not statistically significant (P = 0.274). The respective percentages for low birth weight were 8% and 10.3% for intervention and control groups respectively (P = 0.346). However, the average gestational age at delivery was higher among improved stove users (38 weeks (SD = 8.2) compared to control groups 36.5 weeks (SD = 9.6) with statistically significant difference at 0.91 weeks (95% CI: 0.52 to 1.30 weeks, p < 0.001). The corresponding difference in risk ratio for preterm birth is 0.94 (95% CI:0.92 to 0.97; p < 0.001). The percentages for maternal complications, stillbirth, and miscarriage in the intervention group were not statistically different from the control group.

Conclusions

While the increase in average birth weight among babies born to mothers using improved stoves was not statistically significant, babies had a longer gestational age on average, offering valuable health benefits. However, the study didn’t find a significant impact on other pregnancy outcomes like stillbirth, miscarriage, or maternal complications.

Trial registration

The study was registered at the Pan African Clinical Trial Registry website under the code PACTR202111534227089, (https://pactr.samrc.ac.za/ (Identifier). The first trial registration date was (11/11/2021).
A randomized controlled trial of potential tobacco policies prohibiting menthol flavor in cigarettes and e-cigarettes: a study protocol
Authors: Bold Krysten W. , Sharma Akshika , Haeny Angela , Gueorguieva Ralitza , Buta Eugenia , Baldassarri Stephen , Lempert Lauren , Krishnan-Sarin Suchitra , O’Malley Stephanie
Published: March 2024

Background

Menthol cigarette use remains a large public health problem and disproportionately affects Black adults in the United States. The Food and Drug Administration has proposed prohibiting menthol flavor in cigarettes to protect public health. However, e-cigarettes are available in menthol flavor and are a popular alternative product adults might switch to if menthol is prohibited in cigarettes. Research is needed to understand how availability of menthol (vs. tobacco) flavored e-cigarettes could impact cigarette use among adults who smoke menthol cigarettes.

Methods

We will recruit 150 adults who currently smoke menthol cigarettes and will randomize them to 1 of 3 conditions modeling different regulatory scenarios. We will recruit equal numbers of participants identifying as Black vs. non-Black and will stratify randomization by race. To promote standardization and adherence, cigarette and e-cigarette products will be provided for 8 weeks based on the assigned condition: (A) no menthol restriction (menthol cigarette and menthol flavored e-cigarette), (B) menthol prohibited in cigarettes only (non-menthol cigarette and menthol flavored e-cigarette), (C) menthol prohibited in both cigarettes and e-cigarettes (non-menthol cigarette and tobacco flavored e-cigarette). A follow-up visit will occur at week 12 to assess tobacco use status. The study aims are to (1) examine the impact of prohibiting menthol flavor in cigarettes and e-cigarettes on smoking behavior and (2) investigate whether outcomes differ by race to understand the impact of menthol policies on Black (vs. non-Black) individuals given high rates of menthol cigarette use in this population. The primary outcome will evaluate changes in the number of cigarettes smoked per day during the 8-week study period and will examine differences by regulatory scenario. Secondary outcomes will compare percent days smoke-free, changes in nicotine dependence, and motivation, confidence, and intentions to quit smoking by the regulatory scenarios. We will examine whether changes in the outcomes differ by Black vs. non-Black participants to compare the magnitude of the effect of the various menthol policy scenarios by race.

Discussion

Results will contribute critical information regarding menthol in cigarettes and e-cigarettes to inform regulatory policies that maximize reductions in cigarette smoking and reduce tobacco-related health disparities.

Trial registration

NCT05259566. Yale IRB protocol #2000032211, last approved 12/8/2023.
Associations between school-based fluoride mouth-rinse program, medical-dental expense subsidy policy, and children's oral health in Japan: an ecological study
Authors: Yamamoto Takafumi , Kiuchi Sakura , Ishimaru Miho , Fukuda Hideki , Yokoyama Tetsuji
Published: March 2024

Background

Dental caries are a common non-communicable disease among children. As a public health measure at the prefectural level, school-based fluoride mouth-rinse (S-FMR) program, medical/dental expense subsidy policies, and other factors may reduce the incidence of dental caries and tooth loss. Prefectures focusing on promoting oral health policies may promote both, but the interaction effect of implementing both subsidy policies and S-FMR at the prefectural level on caries prevention has not yet been examined.

Methods

We conducted an ecological study using two-wave panel data, prefecture-level aggregated data in Japan for 2016 and 2018. Coefficient and 95% confidence intervals (CI) were calculated for the dependent variables for oral health using mixed-effects linear regression analysis adjusted for possible confounders. Two dependent variables were used; the standardized claim ratio (SCR) of deciduous tooth extraction and 12-year-olds’ decayed, missing, or filled permanent teeth (DMFT). Four independent variables were S-FMR, the SCR of dental sealants, prefectural income per person, and subsidy policy in three models: co-payment until children enter elementary school (n = 23), no co-payment until children enter elementary school (n = 7), and co-payment continuing beyond elementary school (n = 17). The effects of six interaction terms, each representing a unique pairing from the four independent variables, were individually calculated.

Results

S-FMR was negatively associated with the SCR of deciduous tooth extractions and DMFT (coefficient = -0.11, 95% CI -0.20; -0.01 and coefficient = -0.003, 95% CI -0.005; -0.001, respectively). No co-payment until children enter elementary school was positively associated with the SCR of deciduous tooth extraction compared to co-payment until children enter elementary school(coefficient = 11.42, 95% CI 3.29; 19.55). SCR of dental sealants was positively associated with the SCR of deciduous tooth extractions (coefficient = 0.12, 95% CI 0.06; 0.19) but negatively associated with DMFT (coefficient = -0.001, 95% CI -0.003; -0.0001). Per capita prefectural income was positively associated with the SCR of deciduous tooth extractions(coefficient = 0.01, 95% CI 0.001; 0.02). No interaction was found between S-FMR and the subsidy policy at both outcomes.

Conclusion

High S-FMR utilization and no co-payment until children enter elementary school were associated with fewer deciduous tooth extractions. Also, S-FMR and dental sealant were associated with decreased DMFT.
Outcomes after laparoscopic cholecystectomy in patients older than 80 years: two-years follow-up
Authors: Ramírez-Giraldo Camilo , Venegas-Sanabria Luis Carlos , Rojas-López Susana , Avendaño-Morales Violeta
Published: March 2024

Background

The laparoscopic cholecystectomy is the treatment of choice for patients with benign biliary disease. It is necessary to evaluate survival after laparoscopic cholecystectomy in patients over 80 years old to determine whether the long-term mortality rate is higher than the reported recurrence rate. If so, this age group could benefit from a more conservative approach, such as antibiotic treatment or cholecystostomy. Therefore, the aim of this study was to evaluate the factors associated with 2 years survival after laparoscopic cholecystectomy in patients over 80 years old.

Methods

We conducted a retrospective observational cohort study. We included all patients over 80 years old who underwent laparoscopic cholecystectomy. Survival analysis was conducted using the Kaplan‒Meier method. Cox regression analysis was implemented to determine potential factors associated with mortality at 24 months.

Results

A total of 144 patients were included in the study, of whom 37 (25.69%) died at the two-year follow-up. Survival curves were compared for different ASA groups, showing a higher proportion of survivors at two years among patients classified as ASA 1–2 at 87.50% compared to ASA 3–4 at 63.75% (p = 0.001). An ASA score of 3–4 was identified as a statistically significant factor associated with mortality, indicating a higher risk (HR: 2.71, CI95%:1.20–6.14).

Conclusions

ASA 3–4 patients may benefit from conservative management due to their higher risk of mortality at 2 years and a lower probability of disease recurrence.
A contemporary comparison of laparoscopic versus open partial nephrectomy for renal cell carcinoma
Authors: Nicaise Edouard , Feldman Adam S. , Gusev Andrew , Yu Alice , Nimmagadda Naren , Wszolek Matthew F. , McGovern Francis , Blute Michael L. , Dahl Douglas M.
Published: March 2024

Purpose

To analyze surgical and oncologic outcomes of patients undergoing open partial nephrectomy (OPN) versus laparoscopic partial nephrectomy (LPN) for treatment of renal cell carcinoma (RCC).

Methods

We retrospectively investigated our institutional RCC database for patients who underwent PN for RCC from 1997 to 2018. Decision for technique was at the discretion of the operating urologist, following practice patterns and training history. Outcomes analyzed included pre/peri/post-operative parameters, pathologic outcomes, and disease recurrence rates.

Results

1088 patients underwent PN from 1997 to 2018. After exclusionary criteria, 631 patients who underwent 647 unique PNs for a total of 162 OPN and 485 LPN remained. Baseline, pre-op, and pathologic characteristics were not statistically different. Surgical time was lower in laparoscopic cases [185 vs. 205 min] (p = 0.013). Margin involvement was not statistically different; LPN had lower estimated blood loss (EBL) [150 vs. 250 mL] (p < 0.001) and longer ischemia time [21 vs. 19 min] (p = 0.005). LPN had shorter length of stay [2 vs. 4 days] (p < 0.001), fewer overall complications (p < 0.001), and no significant difference in high-grade complications [2.89 vs. 4.32%] (p = 0.379). Fewer LPN patients developed metastases [1.65 vs. 4.94%] (p = 0.0499). Local recurrence rates were not statistically different [1.24 vs. 3.09%] (p = 0.193). Renal function was equivalent between cohorts post-operatively.

Conclusion

Long-term oncologic outcomes were not significantly different between LPN versus OPN, with no statistical difference in patient and tumor characteristics. LPN was associated with lower EBL, shorter length of stay, and lower overall complication risk. Renal function was not significantly different between cohorts.
CME providers’ experiences and practices in Pakistan: a case study
Authors: Vakani Farhan Saeed , Demirkol Apo , Uebel Kerry , Balasooriya Chinthaka
Published: March 2024

Background

Pakistan has made numerous attempts to establish and implement a national mandatory CME program which currently do not exist. The purpose of this study is to explore the views of major CME providers in order to identify possible strengths and weaknesses in the current program, and offer evidence-based recommendations to help further enhance the national CME program in Pakistan.

Methods

An exploratory study design using a case study approach through in depth interviews was conducted to examine CME providers’ experiences and perceptions. The study was conducted in Pakistan between August and November 2019 with CME providers from Sindh, Punjab, the North-West Frontier Province, and the Federal Capital Territory. Thirty-six providers recognised by the Pakistan Medical and Dental Council who were involved in providing CME activities at the national level and whose contact information was publicly available on their websites, were selected for the study. Of the 36 providers invited, 22 participated in this study.

Results

The results generated several organising themes grouped into three major themes: (1) CME current practices, (2) CME past experiences, and (3) Future developments.

Conclusion

Participants recommended needs-based educational activities for physicians, a well-structured central regulatory CME body collaborating with existing providers, involving experienced providers for rural CME, accrediting diverse local providers, limiting commercial entities’ role, and implementing CME with proper preparation and a phased approach.
Illustration of self-perceived knowledge, skills, and interests in undergraduate dental students using a visual metaphor– results of a monocentric cross-sectional study
Authors: Schmalz Gerhard , Büchi Stefan , Haak Rainer , Ziebolz Dirk , Strauß Maria
Published: March 2024

Background

Self-assessment and self-reflection of competencies are crucial skills for undergraduate students. This monocentric cross-sectional study aims to assess the self-perceived knowledge, skills and interests in conservative dentistry and periodontology of third-, fourth-, and fifth-year dental students by the Pictorial Representation of Illness and Self-measure (PRISM).

Methods

Seventy-five undergraduate dental students (n = 25 of each year) who studied between 2021 and 2022 at the Department of Cariology, Endodontology and Periodontology at the University of Leipzig, Germany, were included. All of them underwent a PRISM-based interview regarding their perceived knowledge, practical skills, and interests in conservative dentistry as well as its sub-disciplines. The distances in the PRISM task (in millimeters) were measured and compared between the groups. Spearman’s Rho was used to reveal correlations between knowledge, skills, and interests in the cohort.

Results

Perceived theoretical knowledge and practical skills differed significantly between groups for the sub-disciplines periodontology, cariology, restorative dentistry and preventive dentistry (p < 0.05). However, students’ interests did not significantly vary between groups (p > 0.05). In the field of conservative dentistry and its sub-disciplines, significant moderate to high positive correlations were found between knowledge and skills (p < 0.01), and weak to moderate positive correlations were found between interests and knowledge (p < 0.05). Regarding the relationship between perceived interests and skills, only restorative dentistry, endodontology and periodontology were significant and only moderate to weak correlations were found (p < 0.05).

Conclusion

PRISM revealed differences in perceived knowledge and skills between third-, fourth-, and fifth-year dental students. Correlations were found between perceived knowledge and skills, as well as between interests and knowledge. PRISM may be a promising tool to support students and teachers in dental education.
The influence of n-3 polyunsaturated fatty acids on cognitive function in individuals without dementia: a systematic review and dose–response meta-analysis
Authors: Suh Seung Wan , Lim Eunji , Burm Suh-Yuhn , Lee Hyungji , Bae Jong Bin , Han Ji Won , Kim Ki Woong
Published: March 2024

Background

Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been suggested as a cognitive enhancing agent, though their effect is doubtful. We aimed to examine the effect of n-3 PUFA on the cognitive function of middle-aged or older adults without dementia.

Methods

We reviewed randomized controlled trials of individuals aged 40 years or older. We systematically searched PubMed/MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane Library databases. We used the restricted cubic splines model for non-linear dose–response meta-analysis in terms of the standardized mean difference with 95% confidence intervals.

Results

The current meta-analysis on 24 studies (n 9660; follow-up 3 to 36 months) found that the beneficial effect on executive function demonstrates an upward trend within the initial 12 months of intervention. This effect is prominently observed with a daily intake surpassing 500 mg of n-3 PUFA and up to 420 mg of eicosapentaenoic acid (EPA). Furthermore, these trends exhibit heightened significance in regions where the levels of blood docosahexaenoic acid (DHA) + EPA are not very low.

Conclusions

Supplementation of n-3 PUFA may confer potential benefits to executive function among the middle-aged and elderly demographic, particularly in individuals whose dietary DHA + EPA level is not substantially diminished.