bluuebunny/crossref_metadata_2025 huggingface dataset:
Multilayered Immunity by Tissue-Resident Lymphocytes in Cancer
Authors: Li Ming O. , Zhang Jing , Xu Zijian , Zhang Xian , Li Peng , Cornish Andrew E.
Published: March 2024

Lymphocytes spanning the entire innate-adaptive spectrum can stably reside in tissues and constitute an integral component of the local defense network against immunological challenges. In tight interactions with the epithelium and endothelium, tissue-resident lymphocytes sense antigens and alarmins elicited by infectious microbes and abiotic stresses at barrier sites and mount effector responses to restore tissue homeostasis. Of note, such a host cell–directed immune defense system has been recently demonstrated to surveil epithelial cell transformation and carcinoma development, as well as cancer cell metastasis at selected distant organs, and thus represents a primordial cancer immune defense module. Here we review how distinct lineages of tissue-resident innate lymphoid cells, innate-like T cells, and adaptive T cells participate in a form of multilayered cancer immunity in murine models and patients, and how their convergent effector programs may be targeted through both shared and private regulatory pathways for cancer immunotherapy.
Disability in Political Science
Authors: Heffernan Ann K.
Published: March 2024

Despite increasing interest in recent years, disability remains a neglected area of study within mainstream political science. Beginning with a brief overview of the ways that disability studies scholars have defined disability, I address the issues that have arisen in trying to measure disability as well as the limits and possibilities that follow from thinking of people with disabilities as a minority group with defined political beliefs and interests. To the extent that much of the work on disability in political science looks to the research on gender, race, ethnicity, and class as a touchstone, I consider the lessons that might be drawn from this work both as it relates to disability as a social category and regarding efforts to conceive of disability and ability in more structural and ideological terms. Turning to the literature on disability in political theory, I examine the ways that disability has been deployed to reveal the ableist assumptions that pervade canonical and more contemporary texts. I conclude by highlighting avenues for future research, including whether it is possible—or, indeed, desirable—to move beyond the civil rights and identity-based frameworks that have so defined disability politics and organizing.
Determinants of Evidence Implementation by Nurses: #Evidencer Model for the Use of Evidence-Based Practice (#EvidencerMUSEBP)—A Structural Equation Model
Authors: Ruzafa-Martínez Maria , Fernández-Salazar Serafin , Leal-Costa César , Ramos-Morcillo Antonio Jesús
Published: February 2024

Existing studies have identified specific factors influencing some dimensions of evidence-based practice (EBP) competence and use. However, the way these factors interact still needs to be clarified. The purpose of the study was to test a model based on the Determinant Frameworks that explain the relationships and the direct pathways between the characteristics of the nurses, the context, and the implementation strategies and the dimensions of EBP competence, attitude, knowledge, skills, and use of EBP. A cross-sectional study was carried out in Spain during January and February 2020, involving 2,370 nurses employed in public health centers across all autonomous communities within the National Health System. An online survey was administered to gather data, addressing various topics related to the nurses’ characteristics, the context in which they worked, the implementation strategy, and their competence in evidence-based practice (EBP). As depicted in the conceptual framework, a structural equation model was constructed to test the hypothesized relationships among key study variables. The model obtained showed a good fit (χ2/df = 3.20, p<0.001; RMSEA = 0.030 [90% CI 0.025, 0.036]; CFI = 0.989; GFI = 0.990; TLI = 0.983). The context, more specifically, the dimensions of nurse participation in the center’s affairs, nursing foundations for quality of care, nurse manager ability leadership and support of nurses, and implementation strategy have a direct and positive effect on EBP use. Training in EBP, reading scientific articles, and having a doctorate are associated with higher competence and knowledge in EBP. The final fit shows the #Evidencer model for the use of EBP (#EvidencerMUSEBP) with two main components: the contextual and strategic factors that influence the implementation of EBP and the characteristics of the professionals, such as their training and reading of articles, which have an impact on EBP competence. This model could guide healthcare organizations in proposing comprehensive interventions to improve EBP use and the competency of nurses.
Acute Abdomen in Pregnancy due to Idiopathic Chylous Ascites
Authors: Epelde Claudia , Saravia Fátima , Aguinaga Mónica , Toledo Ane , Lekuona Arantza , Gorostidi Mikel
Published: March 2024

Chylous ascites results from the leakage of lymph rich in lipids into the peritoneal cavity and represents an exceedingly rare event in the course of pregnancy. While there are numerous documented instances of this pathology manifesting with hypogastric or diffuse abdominal pain, our report highlights a unique presentation involving a 35-week pregnant woman experiencing severe epigastric pain unrelated to pregnancy-induced hypertension or other gastrointestinal disorders. Major acute obstetric pathologies were ruled out, and there was no evidence of fetal distress. Due to uncontrolled pain with an unidentified etiology and an unfavorable Bishop score, an urgent cesarean section was performed. A copious amount of milky fluid was observed during the surgery, subsequently confirmed as chylous in nature. Both the newborn and the mother had positive outcomes postsurgery. Although it is usually a benign condition, it is important for healthcare professionals to be aware of this entity in order to provide timely medical care and administer appropriate treatment.
Experimental and Numerical Investigation of Cavitation Assessment for Runner Blades in a Francis Turbine
Authors: Noon Adnan Aslam , Sharif Aamer , Getachew Melkamu Tadesse , Muhammad Riaz
Published: March 2024

Cavitation in hydro turbines causes component deterioration that requires continuous and costly maintenance in the hydroelectric power generation stations. The Tarbela Dam Hydel Project (TDHP) in Pakistan is facing a cavitation problem in the Francis Turbine components, such as the runner and draft tube. Simulation work has been performed to examine and quantify the cavitation rate as a function of the suction head (SH) and flow velocity (FV) by utilizing a homogeneous cavitation model. The result shows that pressure fluctuation is maximum for overcrowded conditions and minimum for rated load conditions. Moreover, a higher cavitation rate is found for the part and overcrowded conditions compared to the rated load condition. Additionally, the cavitation rate becomes 50% higher when the SH increases from 5.54 to 12.34 m. Moreover, SEM results have verified the CFD results that higher FV and SH enhance the cavitation rate. Furthermore, the numerical work is validated by simplified hydrofoil geometry. The computational fluid dynamics results presented a good arrangement with the experimental data.
Data from The Salivary Microbiome and Predicted Metabolite Production Are Associated with Barrett's Esophagus and High-Grade Dysplasia or Adenocarcinoma
Authors: Solfisburg Quinn S. , Baldini Federico , Baldwin-Hunter Brittany , Austin George I. , Lee Harry H. , Park Heekuk , Freedberg Daniel E. , Lightdale Charles J. , Korem Tal , Abrams Julian A.
Published: March 2024

AbstractBackground:
Esophageal adenocarcinoma (EAC) is rising in incidence, and established risk factors do not explain this trend. Esophageal microbiome alterations have been associated with Barrett's esophagus (BE) and dysplasia and EAC. The oral microbiome is tightly linked to the esophageal microbiome; this study aimed to identify salivary microbiome-related factors associated with BE, dysplasia, and EAC.
Methods:
Clinical data and oral health history were collected from patients with and without BE. The salivary microbiome was characterized, assessing differential relative abundance of taxa by 16S rRNA gene sequencing and associations between microbiome composition and clinical features. Microbiome metabolic modeling was used to predict metabolite production.
Results:
A total of 244 patients (125 non-BE and 119 BE) were analyzed. Patients with high-grade dysplasia (HGD)/EAC had a significantly higher prevalence of tooth loss (P = 0.001). There were significant shifts with increased dysbiosis associated with HGD/EAC, independent of tooth loss, with the largest shifts within the genus Streptococcus. Modeling predicted significant shifts in the microbiome metabolic capacities, including increases in L-lactic acid and decreases in butyric acid and L-tryptophan production in HGD/EAC.
Conclusions:
Marked dysbiosis in the salivary microbiome is associated with HGD and EAC, with notable increases within the genus Streptococcus and accompanying changes in predicted metabolite production. Further work is warranted to identify the biological significance of these alterations and to validate metabolic shifts.
Impact:
There is an association between oral dysbiosis and HGD/EAC. Further work is needed to establish the diagnostic, predictive, and causal potential of this relationship.
Diffsig: Associating Risk Factors with Mutational Signatures
Authors: Park Ji-Eun , Smith Markia A. , Van Alsten Sarah C. , Walens Andrea , Wu Di , Hoadley Katherine A. , Troester Melissa A. , Love Michael I.
Published: March 2024

Background:

Somatic mutational signatures elucidate molecular vulnerabilities to therapy, and therefore detecting signatures and classifying tumors with respect to signatures has clinical value. However, identifying the etiology of the mutational signatures remains a statistical challenge, with both small sample sizes and high variability in classification algorithms posing barriers. As a result, few signatures have been strongly linked to particular risk factors.

Methods:

Here, we develop a statistical model, Diffsig, for estimating the association of one or more continuous or categorical risk factors with DNA mutational signatures. Diffsig takes into account the uncertainty associated with assigning signatures to samples as well as multiple risk factors' simultaneous effect on observed DNA mutations.

Results:

We applied Diffsig to breast cancer data to assess relationships between five established breast-relevant mutational signatures and etiologic variables, confirming known mechanisms of cancer development. In simulation, our model was capable of accurately estimating expected associations in a variety of contexts.

Conclusions:

Diffsig allows researchers to quantify and perform inference on the associations of risk factors with mutational signatures.

Impact:

We expect Diffsig to provide more robust associations of risk factors with signatures to lead to better understanding of the tumor development process and improved models of tumorigenesis.
Supplementary Figure 2 from Single-Cell RNA-Seq Analysis of Patient Myeloid-Derived Suppressor Cells and the Response to Inhibition of Bruton's Tyrosine Kinase
Authors: Savardekar Himanshu , Allen Carter , Jeon Hyeongseon , Li Jianying , Quiroga Dionisia , Schwarz Emily , Wu Richard C. , Zelinskas Sara , Lapurga Gabriella , Abreo Alexander , Stiff Andrew , Shaffer Jami , Blaser Bradley W. , Old Matthew , Wesolowski Robert , Xin Gang , Kendra Kari L. , Chung Dongjun , Carson William E.
Published: March 2024

UMAP of the cell clusters in purified MDSC.
Abstract A015: Multiplexed live-cell imaging for drug responses in patient-derived organoid models of endometrial cancer
Authors: Colling Kaitriana E. , Symons Emily L. , Sumanasiri Hiruni K. , Thiel Kristina W.
Published: March 2024

Patient-derived organoid (PDO) models of endometrial cancer are rapidly emerging as a multifunctional research model to recapitulate in vivo cancer progression and therapeutic response. PDO models are generated by reconstituting patient tumor cells in extracellular basement membrane extract (BME) and culturing as three-dimensional domes supplemented with a specialized niche of growth factors. Despite the rise in popularity of PDO models to assess drug response in vitro, there are limited commercially available reagents that are compatible with BME. In addition, most reagents are endpoint assays that require cell lysis, which is problematic because PDOs are a limited resource. Reducing drug response assessment to a single timepoint misses out on valuable kinetic response data, and samples cannot be used for subsequent downstream analyses, such as RNA sequencing or protein assays. Herein we describe a method to assess drug effects in PDO models using kinetic live-cell imaging. Live-cell imaging is a sophisticated form of automated microscopy that, when combined with fluorescent dyes, has the capacity to quantify multiple cellular responses simultaneously. Importantly, live-cell imaging reagents do not perturb cell viability or induce DNA damage, thereby allowing for accurate repeated assessment of PDO response to treatment over time. In proof-of-concept studies, we first established the utility of this approach to assess the effect of cytotoxic and cytostatic agents in PDO models of endometrial cancer. Specific parameters of interest include PDO number, area, cell health and induction of apoptosis. Agents that produced a cytotoxic effect promoted a decrease in organoid area and number over time, concomitant with an increase in apoptosis as measured by Annexin V staining. Ongoing studies are examining the dose-dependent phenotypic effects of cytostatic agents such as progestins in endometrial cancer PDO models. To evaluate the safety of the compounds, we have also conducted experiments using patient-derived organoids of normal endometrium, which was collected from uninvolved regions of the uterus in cytoreductive surgery. We envision that this automated kinetic imaging platform can be expanded to other phenotypic readouts to better understand diverse therapeutic effects of different classes of drugs under investigation for endometrial cancer.

Citation Format: Kaitriana E. Colling, Emily L. Symons, Hiruni K. Sumanasiri, Kristina W. Thiel. Multiplexed live-cell imaging for drug responses in patient-derived organoid models of endometrial cancer [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr A015.
Abstract B009: Global expression analysis of endometrial cancer cells in response to progesterone identifies new therapeutic targets
Authors: Thiel Kristina , Newtson Andreea , Devor Eric , Zhang Yuping , Malmrose Paige K. , Losh Haley , Davies Suzy , Smith Lane E. , Padilla Jamie , Leiva Stephanie , Hagan Christy , Pufall Miles , Gertz Jay , Guo Yan , Leslie Kimberly K.
Published: March 2024

Progesterone prevents development of endometrial cancers through its receptor (PR) although the molecular mechanisms have yet to be fully characterized. In this study, we performed a global analysis of gene regulation by progesterone using human endometrial cancer cells that expressed PR endogenously or exogenously. We found progesterone strongly inhibits multiple components of the platelet derived growth factor receptor (PDGFR), Janus kinase (JAK), signal transducer and activator of transcription (STAT) pathway through PR. The PDGFR/JAK/STAT pathway signals to control numerous downstream targets including AP-1 transcription factors Fos and Jun. Treatment with inhibitors of the PDGFR/JAK/STAT pathway significantly blocked proliferation in multiple novel patient-derived organoid models of endometrial cancer, and activation of this pathway was found to be a poor prognostic signal for the survival of patients with endometrial cancer from The Cancer Genome Atlas. Our study identifies this pathway as central to the growth-limiting effects of progesterone in endometrial cancer and suggests that inhibitors of PDGFR/JAK/STAT should be considered for future therapeutic interventions.

Citation Format: Kristina Thiel, Andreea Newtson, Eric Devor, Yuping Zhang, Paige K. Malmrose, Haley Losh, Suzy Davies, Lane E. Smith, Jamie Padilla, Stephanie Leiva, Christy Hagan, Miles Pufall, Jay Gertz, Yan Guo, Kimberly K. Leslie. Global expression analysis of endometrial cancer cells in response to progesterone identifies new therapeutic targets [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr B009.
Abstract B022: Conversion from minimally invasive surgical approaches to open surgery among endometrial cancer patients in a national cancer patients’ registry
Authors: Yousif Abdelrahman , Ngo Julie , Abdel-Gadir Deena , Lachance Jenny , Mize Benjamin , Chefetz Ilana
Published: March 2024

Endometrial cancer (EC) ranks as the predominant gynecological malignancy in the US. While minimally invasive surgical (MIS) techniques have revolutionized EC management, conversion to laparotomy remains a concern, with reported rates varying widely. Factors influencing this conversion, including patient characteristics and tumor attributes, have not been fully understood. Addressing this gap, our study employs a national registry to analyze patient, tumor, and surgeon-related factors contributing to the transition from MIS to laparotomy in EC cases. Results: 0ur results showed, 3.4% (135/4028) experienced planned MIS-to-open conversion. Demographic disparities were absent between conversion and MIS groups. Conversion was more prevalent in obese (29%) and morbidly obese (37%) patients (P=0.04), linked to prior abdominal surgery (63% vs 52%; P=0.001). Endometrioid EC predominated (59%) in the converted group, with higher non-endometrioid rates (serous carcinoma 16%, clear cell carcinoma 4%, carcinosarcoma 5%, mixed histology 12%; all P<0.01). Advanced FIGO stages were more common in conversions (stage II: 5%, stage III: 25%, stage IV: 9%; all P<0.001). Type II (24%) and type III (5%) hysterectomies were more frequent in conversions (P<0.001). Logistic regression indicated BMI, prior surgery, FIGO stage, histology, and operation type affected conversion (p<0.001), explaining 12.3% of variance. Indications for conversion included uterine size, adhesions, and disease extent. Conclusion: the adoption of minimally invasive surgery (MIS) has become increasingly popular for managing endometrial cancer (EC), attributed to enhanced perioperative outcomes. However, prudent patient selection and surgical planning are imperative to mitigate the risk of unplanned transition to open surgery. Predictive factors for such conversion include uterine size, prior abdominal surgeries, surgical complexity, disease extent, and histologic types. Further prospective research is warranted to validate these findings and identify individuals at conversion risk. Ultimately, a personalized surgical approach, tailored to individual patient attributes, remains pivotal for optimizing outcomes in EC management.

Citation Format: Abdelrahman Yousif, Julie Ngo, Deena Abdel-Gadir, Jenny Lachance, Benjamin Mize, Ilana Chefetz. Conversion from minimally invasive surgical approaches to open surgery among endometrial cancer patients in a national cancer patients’ registry [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr B022.
Supplementary Data from Which Small Molecule? Selecting Chemical Probes for Use in Cancer Research and Target Validation
Authors: Mader Mary M. , Rudolph Joachim , Hartung Ingo V. , Uehling David , Workman Paul , Zuercher William
Published: February 2024

Figure S1
Supplementary Table 3 from INHBA is Enriched in HPV-negative Oropharyngeal Squamous Cell Carcinoma and Promotes Cancer Progression
Authors: Abou Kors Tsima , Hofmann Linda , Betzler Annika , Payer Kathrina , Bens Martin , Truong Jens , von Witzleben Adrian , Thomas Jaya , Kraus Johann M. , Kalaajieh Randa , Huber Diana , Ezić Jasmin , Benckendorff Julian , Greve Jens , Schuler Patrick J. , Ottensmeier Christian H. , Kestler Hans A. , Hoffmann Thomas K. , Theodoraki Marie-Nicole , Brunner Cornelia , Laban Simon
Published: February 2024

Correlation analysis between miRNAs and INHBA expression output
Supplementary Table 1 from INHBA is Enriched in HPV-negative Oropharyngeal Squamous Cell Carcinoma and Promotes Cancer Progression
Authors: Abou Kors Tsima , Hofmann Linda , Betzler Annika , Payer Kathrina , Bens Martin , Truong Jens , von Witzleben Adrian , Thomas Jaya , Kraus Johann M. , Kalaajieh Randa , Huber Diana , Ezić Jasmin , Benckendorff Julian , Greve Jens , Schuler Patrick J. , Ottensmeier Christian H. , Kestler Hans A. , Hoffmann Thomas K. , Theodoraki Marie-Nicole , Brunner Cornelia , Laban Simon
Published: February 2024

Gene set enrichment analysis output
Supplementary Figure 1 from INHBA is Enriched in HPV-negative Oropharyngeal Squamous Cell Carcinoma and Promotes Cancer Progression
Authors: Abou Kors Tsima , Hofmann Linda , Betzler Annika , Payer Kathrina , Bens Martin , Truong Jens , von Witzleben Adrian , Thomas Jaya , Kraus Johann M. , Kalaajieh Randa , Huber Diana , Ezić Jasmin , Benckendorff Julian , Greve Jens , Schuler Patrick J. , Ottensmeier Christian H. , Kestler Hans A. , Hoffmann Thomas K. , Theodoraki Marie-Nicole , Brunner Cornelia , Laban Simon
Published: February 2024

E-Cadherin Expression upon INHBA knockdown. Representative western blot (of n = 3 replicates) showing E-Cadherin protein expression in Mock KD and INHBA KD1/KD2 at t24 and t48.
FIGURE 9 from INHBA is Enriched in HPV-negative Oropharyngeal Squamous Cell Carcinoma and Promotes Cancer Progression
Authors: Abou Kors Tsima , Hofmann Linda , Betzler Annika , Payer Kathrina , Bens Martin , Truong Jens , von Witzleben Adrian , Thomas Jaya , Kraus Johann M. , Kalaajieh Randa , Huber Diana , Ezić Jasmin , Benckendorff Julian , Greve Jens , Schuler Patrick J. , Ottensmeier Christian H. , Kestler Hans A. , Hoffmann Thomas K. , Theodoraki Marie-Nicole , Brunner Cornelia , Laban Simon
Published: February 2024

Correlation analyses between INHBA expression, immune infiltrates and miRNAs. A, Waterfall plot showing Spearman correlation between INHBA expression level and infiltrating ratios (IR) of different immune cells, as computed by immune cell deconvolution. Rho > 0.4 was considered relevant (dashed line). *, P ≤ 0.05; ***, P ≤ 0.001; ns, not significant. B, Correlation matrix between INHBA and the pro-tumor M1 signature showing Spearman rho and P-value symbols (*, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.001) in the upper triangular matrix and scatter plots in the lower triangular matrix. TPM = transcripts per million. C, Waterfall plot showing Spearman correlation between INHBA expression level and miRNAs (TCGA cohort). miRNAs with Rho < −0.4 and P < 0.05 were considered relevant (dashed line). D, Venn diagram showing intersections between negatively correlating miRNAs from C and miRNAs predicted to interact with the 3′UTR of INHBA by miRDB and Targetscan resulting in three candidates of interest (hsa-mir-106a, hsa-mir-20b, hsa-mir-9-1/2/3). Their putative binding sites to the INHBA 3′UTR are highlighted. E–G, Kaplan–Meier plots with log-rank test for overall survival of patients with OPSCC (TCGA cohort) based on tumor miRNA expression of the outlined candidates (E: hsa-mir-106a, F: hsa-mir-20b, G: hsa-mir-9). Blue indicates low and red indicates high miRNA expression, as determined using median of raw counts as cutoff.
FIGURE 5 from INHBA is Enriched in HPV-negative Oropharyngeal Squamous Cell Carcinoma and Promotes Cancer Progression
Authors: Abou Kors Tsima , Hofmann Linda , Betzler Annika , Payer Kathrina , Bens Martin , Truong Jens , von Witzleben Adrian , Thomas Jaya , Kraus Johann M. , Kalaajieh Randa , Huber Diana , Ezić Jasmin , Benckendorff Julian , Greve Jens , Schuler Patrick J. , Ottensmeier Christian H. , Kestler Hans A. , Hoffmann Thomas K. , Theodoraki Marie-Nicole , Brunner Cornelia , Laban Simon
Published: February 2024

Cell proliferation upon INHBA knockdown. A, Proliferation of native UDSCC1 cells, Mock KD, INHBA KD1/KD2 and native UDSCC2 cells as assessed by carboxyfluorescein succinimidyl ester (CFSE) assay and flow cytometry. Results are shown as mean ± SD of the ΔMFI (mean fluorescence intensity) normalized to UDSCC1 between t0 and t24, or t0 and t48 (n = 3). Conditions were compared with native UDSCC1 using unpaired t test with ***, P ≤ 0.001; ****, P ≤ 0.0001; and ns, P > 0.05. B, Representative flow cytometry histograms for each condition with the right peak representing t0, central peak representing t24 and left peak representing t48.
FIGURE 4 from INHBA is Enriched in HPV-negative Oropharyngeal Squamous Cell Carcinoma and Promotes Cancer Progression
Authors: Abou Kors Tsima , Hofmann Linda , Betzler Annika , Payer Kathrina , Bens Martin , Truong Jens , von Witzleben Adrian , Thomas Jaya , Kraus Johann M. , Kalaajieh Randa , Huber Diana , Ezić Jasmin , Benckendorff Julian , Greve Jens , Schuler Patrick J. , Ottensmeier Christian H. , Kestler Hans A. , Hoffmann Thomas K. , Theodoraki Marie-Nicole , Brunner Cornelia , Laban Simon
Published: February 2024

Cell migration upon INHBA knockdown. A, Migration of native UDSCC1 cells, Mock KD, INHBA KD1/KD2 and native UDSCC2 cells as assessed by scratch assay. Results are shown as mean ± SD of the open wound area (n = 3) at baseline (t0), t24, and t48. Conditions were compared with native UDSCC1 using unpaired t test with ***, P ≤ 0.001; ****, P ≤ 0.0001; and ns, P > 0.05. B, Representative images of processed light microscopy pictures taken at 10-fold magnification of each condition at t0, t24, and t48.
FIGURE 3 from INHBA is Enriched in HPV-negative Oropharyngeal Squamous Cell Carcinoma and Promotes Cancer Progression
Authors: Abou Kors Tsima , Hofmann Linda , Betzler Annika , Payer Kathrina , Bens Martin , Truong Jens , von Witzleben Adrian , Thomas Jaya , Kraus Johann M. , Kalaajieh Randa , Huber Diana , Ezić Jasmin , Benckendorff Julian , Greve Jens , Schuler Patrick J. , Ottensmeier Christian H. , Kestler Hans A. , Hoffmann Thomas K. , Theodoraki Marie-Nicole , Brunner Cornelia , Laban Simon
Published: February 2024

INHBA expression in OPSCC tumor and cell lines and its correlation with EMT transcription factors. Correlation of INHBA expression with the expression of SNAI1 (A), SNAI2 (B), and TWIST1 (C) in OPSCC tumors (Ulm cohort). TPM = transcripts per million. D, Relative expression of INHBA mRNA in native UDSCC1 (HPV-negative) and UDSCC2 (HPV-positive) cells as determined by qRT-PCR and normalized to RPL30 and UDSCC1. Results are shown as mean ± SD of n = 6 replicates. INHBA expression was not detected in n = 3 UDSCC2 samples. Expression level between UDSCC1 and UDSCC2 was compared by unpaired t test with **, P ≤ 0.01. E, Representative Western blot analysis (of n = 3 replicates) showing INHBA protein expression in native UDSCC1 and UDSCC2 cells. Numbers below blots indicate relative INHBA intensity normalized to GAPDH. F, Relative expression of INHBA, SNAI1, SNAI2, and TWIST1 mRNA in UDSCC1 cells upon transfection with Mock siRNA [Mock knockdown (KD)] and two INHBA siRNAs (INHBA KD1 and KD2) after 24 hours (t24) and 48 hours (t48). Target gene expression was determined by qRT-PCR and normalized to RPL30 and Mock KD. Results are shown as mean ± SD of n = 3 replicates. Expression level between Mock KD and INHBA KD1/2 was compared by unpaired t test with *, P ≤ 0.05; **, P ≤ 0.01; and ns, P > 0.05. G, Representative Western blot analysis (of n = 3 replicates) showing INHBA protein expression in Mock KD and INHBA KD1/KD2 at t24 and t48. Numbers below blots indicate relative INHBA intensity normalized to GAPDH.
FIGURE 1 from INHBA is Enriched in HPV-negative Oropharyngeal Squamous Cell Carcinoma and Promotes Cancer Progression
Authors: Abou Kors Tsima , Hofmann Linda , Betzler Annika , Payer Kathrina , Bens Martin , Truong Jens , von Witzleben Adrian , Thomas Jaya , Kraus Johann M. , Kalaajieh Randa , Huber Diana , Ezić Jasmin , Benckendorff Julian , Greve Jens , Schuler Patrick J. , Ottensmeier Christian H. , Kestler Hans A. , Hoffmann Thomas K. , Theodoraki Marie-Nicole , Brunner Cornelia , Laban Simon
Published: February 2024

GSEA identifying INHBA as a leading driver of EMT in HPV-negative tumors. A, Dot plot of pathways enriched and depleted in HPV-negative compared with HPV-positive OPSCC tumor as determined by GSEA of transcriptomes from n = 62 primary tumor samples (Ulm cohort). Results were ranked according to the NES, dots were colored according to FDR and size was determined by the number of genes. B, GSEA plot of the top pathway (EMT) showing enrichment score (green curve), position of genes (black lines) with the leading edge (p-EMT), NES, and FDR. C, Volcano plot showing the log2 fold change of genes upregulated in HPV-positive (red) and HPV-negative OPSCC (blue), with INHBA (red circle) as the highest upregulated leading edge in HPV-negative tumors.
Factors Influencing Long-Term Outcomes of Single-Session Gamma Knife Radiosurgery in Large-Volume Meningiomas >10 cc
Authors: Goyal-Honavar Abhijit , Pateriya Vibhor , Chauhan Sonal , Sadashiva Nishanth , Vazhayil Vikas , Konar Subhas , Beniwal Manish , AR Prabhuraj , Arimappamagan Arivazhagan , B Jeeva , Natesan Ponnusamy
Published: March 2024

Introduction: Meningiomas are the most common primary intracranial tumour. Gamma knife radiosurgery (GKRS) is a frequently employed non-invasive method of treatment, with good remission rates and low morbidity in literature. However, the role of GKRS in the management of “large” meningiomas is unclear, with reported outcomes that vary by centre. We aimed to assess the factors that influence long-term outcomes following GKRS in meningiomas >10 cc in volume. Methods: A retrospectively analysed all patients with meningiomas exceeding 10 cc in volume who underwent GKRS between January 2006 and December 2021 at the National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru. Demographic, clinical, radiological, and follow-up data were acquired, and factors associated with progression following GKRS were assessed. Results: The cohort comprised 76 patients 29 males (38.2%) and 47 females (61.8%) with a mean age of 46.3 ± 11.02 years. Thirty-nine patients had been previously operated (51.3%). Meningiomas were most frequently located in the parasagittal region (26 tumours, 34.2%) and sphenopetroclival region (23 tumours, 30.3%), with mean lesion volume of 12.55 ± 5.22 cc, ranging 10.3 cc–25 cc. The mean dose administered to the tumour margin was 12.5 Gy ± 1.2 Gy (range 6–15 Gy). The median duration of clinical follow-up was 48 months, over which period radiological progression occurred in 14 cases (20%), with unchanged tumour volume in 20 cases (28.6%) and reduction in size of the tumour in 36 cases (51.4%). Progression-free survival after GKRS was 72% at 5 years, was significantly poorer among meningiomas with tumour volume >14 cc (log-rank test p = 0.045), tumours presenting with limb motor deficits (log-rank test p = 0.012), and tumours that underwent prior Simpson grade 3 or 4 excision (log-rank test p = 0.032). Conclusions: Meningiomas >10 cc in volume appear to display a high rate of progression and subsequent need for surgery following GKRS. Primary surgical resection, when not contraindicated, may be considered with GKRS serving an adjuvant role, especially in tumours exceeding 14 cc in volume, and presenting with limb motor deficits. Long-term clinical and radiological follow-up is essential following GKRS as the response of large meningiomas may be unpredictable.
Balloon Dilatation for Bronchoscope Delivery in a Swine Model: A Novel Technique for Ultra-Peripheral Lung Field Access and Accurate Biopsy
Authors: Miyake Kotaro , Shiroyama Takayuki , Satoh Shingo , Adachi Yuichi , Ohira Kika , Abe Yuko , Takata So , Masuhiro Kentaro , Naito Yujiro , Hirata Haruhiko , Nagatomo Izumi , Takeda Yoshito , Kumanogoh Atsushi
Published: March 2024

Introduction: In transbronchial biopsy of peripheral pulmonary lesions, the bronchoscope can reach only a limited depth due to the progressive narrowing of bronchi, which may reduce the diagnostic rate. This study examined the balloon dilatation for bronchoscope delivery (BDBD) technique, employing a novel balloon device to enhance bronchoscopy into the peripheral lung areas. Methods: Anaesthetised swine served as our primary model. Using computed tomography (CT) scans, we positioned virtual targets characterised by a positive bronchus sign and a diameter of 20 mm beneath the pleura. The bronchoscope was navigated along the pathways determined from the CT images. We performed balloon dilatation when bronchial narrowing obstructed progress to assess whether balloon dilatation would enable the bronchoscope to enter further into the periphery. Results: We established 21 virtual targets on the CT scans. An average of 12.1 branches were identified along the pathways on the CT scans; however, bronchoscopy without BDBD only allowed access to an average of 6.7 branches. Based on 72 balloon dilatations with 3.0-mm or 4.0-mm ultra-thin bronchoscopes, there was an average increased access of 3.43 and 5.14 branches per route, respectively, with no significant BDBD complications. The bronchoscope was able to reach the planned location along all pathways, and the mean final bronchoscopic endpoints were at an average distance of 14.7 mm from the pleura. Post-procedure CT confirmed biopsy accuracy. Conclusion: The BDBD technique can enhance access of a flexible bronchoscope into the peripheral lung fields, which could potentially allow more accurate transbronchial interventions for peripheral targets.
Sistematika Penyusunan Dokumen Manual Sistem Jaminan Produk Halal
Authors: Kusuma Titis Sari , Kurniawati Adelya Desi , Iastika Aulia Riska
Published: February 2024

Sesuai Amanah Undang-Undang nomor 33 tahun 2014, Penerapan kewajiban sertifikasi halal akan resmi dimulai pada 17 Oktober 2024 untuk makanan, minuman, produk penyembelihan dan jasa penyembelihan, bahan baku, bahan tambahan pangan, dan bahan penolong makanan dan minuman. Oleh karena itu, para pelaku usaha baik usaha mikro dan kecil, usaha menengah, dan usaha besar sudah mulai mengajukan pengurusan sertifikat halal. Dokumen pengajuan sertifikat halal ini disebut Manual Sistem Jaminan Produk Halal sesuai Surat Edaran Badan Penyelenggara Jaminan Produk Halal nomor B-5952/BD.II/P.II.1.2/HM.00/09/2021 tentang Penggunaan Template Manual Sistem Jaminan Produk Halal. Didalam surat edaran tersebut telah memuat 5 kriteria Sistem Jaminan Produk Halal (SJPH) (Komitmen dan tanggung jawab, Bahan, Proses Produk Halal, Produk, dan Pemantauan dan Evaluasi) dimana terdapat 17 (tujuh belas) lampiran yang harus dilengkapi oleh pelaku usaha disertai dengan bukti dokumen pendukungnya sebagai persyaratan mendapatkan sertifikat halal. Namun, tidak semua pelaku usaha memahami cara pengisian dokumen tersebut, sehingga menyebabkan proses pengurusan sertifikat halal menjadi lama karena pelaku usaha harus melengkapi dokumen yang dibutuhkan sampai benar-benar lengkap untuk mempelancar proses audit. Buku ini membahas mengenai sistematika penyusunan Manual Sistem Jaminan Produk Halal yang membahas mulai regulasi yang harus dipahami oleh pelaku usaha, 5 kriteria Sistem Jaminan Produk Halal (SJPH) (Komitmen dan tanggung jawab, Bahan, Proses Produk Halal, Produk, dan Pemantauan dan Evaluasi), dokumen- dokumen yang harus dilengkapi oleh pelaku usaha, beserta contoh dokumennya. Pembahasan pada keseluruhan isi buku ini diharapkan dapat memberikan gambaran kepada pelaku usaha dan penyelia halal dalam Menyusun dokumen Manual Sistem Jaminan Produk Halal sehingga proses pengajuan sertifikat halal dapat lebih cepat dan segera mendapatkan sertifikat halal dari BPJPH. Buku ini dapat dibaca oleh pelaku usaha usaha kecil dan mikro, menengah, dan besar, pelaku usaha dibidang perhotelan, katering, Rumah Sakit yang hendak mengajukan sertifikasi halal, para penyelia halal, dan auditor halal. Buku ini juga bisa dibaca oleh para pengajar (Guru dan Dosen) di bidang halal, mahasiswa yang menempuh mata kuliah terkait halal. Harapannya, buku ini dapat menambah khazanah keilmuan tentang halal khususnya penyusunan dokumen Manual Sistem Jaminan Produk Halal sehingga dapat diterapkan dalam penyusunan dokumen dengan baik serta meningkatkan pemahaman tentang halal.
Manajemen Breeding dan Penetasan Unggas
Authors: Yulianti Dyah Lestari , Prayogi Heni Setyo , Hamiyanti Adelina Ari , Nurwahyuni Eka , Andri Faizal , Marwi Filoza
Published: February 2024

Buku Ajar Manajemen Breeding dan Penetasan Unggas adalah referensi bagi mahasiswa yang memprogram mata kuliah Manajemen Breeding dan Penetasan Unggas. Mata kuliah tersebut menyusun struktur Kurikulum Program Studi Peternakan Fakultas Peternakan Universitas Brawijaya 2020. Buku Ajar Manajemen Breeding dan Penetasan Unggas terbagi menjadi dua bagian. Bagian pertama mengulas tentang Manajemen Breeding dan bagian kedua mengulas tentang Manajemen Penetasan. Komoditas ternak difokuskan pada manajemen breeding farm dan penetasan ayam ras. Peternakan unggas dikembangkan oleh masyarakat dengan berbagai tujuan. Breeding farm unggas bertujuan untuk mengembangbiakkan unggas agar populasi cukup untuk memenuhi kebutuhan protein bewani masyarakat. Bagian satu pada buku ini dengan rinci memberikan penjelasan tentang manajemen breeding yang meliputi bibit, manajemen perkandangan, manajemen pakan, manajemen pemeliharaan, manajemen pencegahan penyakit, serta monitoring dan evaluasi. Bagian kedua buku ini memberikan penjelasan tentang manajemen penetasan yang menguraikan tentang biosecurity, manajemen telur tetas, operasional mesin tetas, manajemen penetasan, monitoring, dan evaluasi penetasan.
Metabolomic Association and Risk Prediction With Heart Failure in Older Adults
Authors: Liu Guning , Nguyen Ngoc Quynh H. , Wong Kari E. , Agarwal Sunil K. , Boerwinkle Eric , Chang Patricia P. , Claggett Brian L. , Loehr Laura R. , Ma Jianzhong , Matsushita Kunihiro , Rodriguez Carlos J. , Rossi Joseph S. , Russell Stuart D. , Stacey R. Brandon , Shah Amil M. , Yu Bing
Published: March 2024

BACKGROUND:

Older adults have markedly increased risks of heart failure (HF), specifically HF with preserved ejection fraction (HFpEF). Identifying novel biomarkers can help in understanding HF pathogenesis and improve at-risk population identification. This study aimed to identify metabolites associated with incident HF, HFpEF, and HF with reduced ejection fraction and examine risk prediction in older adults.

METHODS:

Untargeted metabolomic profiling was performed in Black and White adults from the ARIC study (Atherosclerosis Risk in Communities) visit 5 (n=3719; mean age, 75 years). We applied Cox regressions to identify metabolites associated with incident HF and its subtypes. The metabolite risk score (MRS) was constructed and examined for associations with HF, echocardiographic measures, and HF risk prediction. Independent samples from visit 3 (n=1929; mean age, 58 years) were used for replication.

RESULTS:

Sixty metabolites (hazard ratios range, 0.79–1.49; false discovery rate, <0.05) were associated with incident HF after adjusting for clinical risk factors, eGFR, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). Mannonate, a hydroxy acid, was replicated (hazard ratio, 1.36 [95% CI, 1.19–1.56]) with full adjustments. MRS was associated with an 80% increased risk of HF per SD increment, and the highest MRS quartile had 8.7× the risk of developing HFpEF than the lowest quartile. High MRS was also associated with unfavorable values of cardiac structure and function. Adding MRS over clinical risk factors and NT-proBNP improved 5-year HF risk prediction C statistics from 0.817 to 0.850 (∆C, 0.033 [95% CI, 0.017–0.047]). The association between MRS and incident HF was replicated after accounting for clinical risk factors (
P
<0.05).

CONCLUSIONS:

Novel metabolites associated with HF risk were identified, elucidating disease pathways, specifically HFpEF. An MRS was associated with HF risk and improved 5-year risk prediction in older adults, which may assist at at-risk population identification.
MBNL1 Regulates Programmed Postnatal Switching Between Regenerative and Differentiated Cardiac States
Authors: Bailey Logan R.J. , Bugg Darrian , Reichardt Isabella M. , Ortaç C. Dessirée , Nagle Abigail , Gunaje Jagadambika , Martinson Amy , Johnson Richard , MacCoss Michael J. , Sakamoto Tomoya , Kelly Daniel P. , Regnier Michael , Davis Jennifer
Published: March 2024

BACKGROUND:

Discovering determinants of cardiomyocyte maturity is critical for deeply understanding the maintenance of differentiated states and potentially reawakening endogenous regenerative programs in adult mammalian hearts as a therapeutic strategy. Forced dedifferentiation paired with oncogene expression is sufficient to drive cardiac regeneration, but elucidation of endogenous developmental regulators of the switch between regenerative and mature cardiomyocyte cell states is necessary for optimal design of regenerative approaches for heart disease. MBNL1 (muscleblind-like 1) regulates fibroblast, thymocyte, and erythroid differentiation and proliferation. Hence, we examined whether MBNL1 promotes and maintains mature cardiomyocyte states while antagonizing cardiomyocyte proliferation.

METHODS:

MBNL1 gain- and loss-of-function mouse models were studied at several developmental time points and in surgical models of heart regeneration. Multi-omics approaches were combined with biochemical, histological, and in vitro assays to determine the mechanisms through which MBNL1 exerts its effects.

RESULTS:

MBNL1 is coexpressed with a maturation-association genetic program in the heart and is regulated by the MEIS1/calcineurin signaling axis. Targeted MBNL1 overexpression early in development prematurely transitioned cardiomyocytes to hypertrophic growth, hypoplasia, and dysfunction, whereas loss of MBNL1 function increased cardiomyocyte cell cycle entry and proliferation through altered cell cycle inhibitor transcript stability. Moreover, MBNL1-dependent stabilization of estrogen-related receptor signaling was essential for maintaining cardiomyocyte maturity in adult myocytes. In accordance with these data, modulating MBNL1 dose tuned the temporal window of neonatal cardiac regeneration, where increased MBNL1 expression arrested myocyte proliferation and regeneration and MBNL1 deletion promoted regenerative states with prolonged myocyte proliferation. However, MBNL1 deficiency was insufficient to promote regeneration in the adult heart because of cell cycle checkpoint activation.

CONCLUSIONS:

Here, MBNL1 was identified as an essential regulator of cardiomyocyte differentiated states, their developmental switch from hyperplastic to hypertrophic growth, and their regenerative potential through controlling an entire maturation program by stabilizing adult myocyte mRNAs during postnatal development and throughout adulthood. Targeting loss of cardiomyocyte maturity and downregulation of cell cycle inhibitors through MBNL1 deletion was not sufficient to promote adult regeneration.
From the Religious Field to the Alternative Field
Authors: Bawidamann Loïc
Published: March 2024

This article examines the link between religion and conspiracy theories by focusing on religious agents operating two alternative media outlets in Switzerland, opposing perceived mainstream opinions. Informed by Bourdieu’s field theory, the article elaborates on the agents’ surpassing of field boundaries, spawning an alternative field that accommodates all agents expelled from their initial fields. Through web scraping and qualitative interviews with the content creators, the analysis elucidates the particular significance of religious agents in the production and distribution of conspiracy theories, as they inherently oppose social differentiation, enabling them to contend with dominant authorities convincingly. The article concludes by offering an understanding of the alternative field and, by extension, of conspiracy theories as a process of dedifferentiation, striving for a realignment of the current structure of society.
Velutinus, a novel genus in Patellariopsidaceae from medicinal plants in Sichuan Province, China
Authors: WU NA , CHETHANA K.W. THILINI , LIU JIAN-KUI
Published: February 2024

Velutinus sichuanensis gen. et sp. nov. was collected from dead branches of the medicinal plant Loropetalum chinense var. rubrum (Hamamelidaceae) in Sichuan Province, China. The genus Velutinus is characterized by having cylindrical, straight or slightly curved, septate, hyaline conidiophores, holoblastic, polyblastic conidiogenous cells, and thick-walled, dark brown, septate, spherical conidia, sometimes with conspicuous appendages. Molecular phylogenetic analyses based on the combined ITS and LSU sequences data showed that Velutinus forms a distinct lineage in Patellariopsidaceae, Helotiales, Leotiomycetes. The new genus, Velutinus is introduced to accommodate V. sichuanensis based on morphological characteristics and multi-gene phylogenetic analyses. Detailed descriptions and illustrations of the new taxa are provided.
Three new species of Cirrothaumatia Razowski & Becker from Peru, with notes on the genus (Lepidoptera: Tortricidae: Tortricinae: Cochylini)
Authors: HEPPNER JOHN B. , BAE YANG-SEOP
Published: February 2024

Three new species of the cochyline genus Cirrothau­matia Razow­ski & Becker, 1986 are described and illustrated from submontane Andean sites in Peru (Depts. Amazonas, Junín, and San Martín): C. pichita n. sp., C. huemboana n. sp., and C. moyobamba n. sp. Comments and illustrations are provided for the three previously described species from southern Mexico (Vera­cruz), Central America (Guatemala, Costa Rica, and Panama), and northern South America (Venezuela: Edo. Aragua; Ecuador: Pichin­cha Prov.).
New species of the wasp-mimic Parahephaestion Melzer, 1930 (Coleoptera: Cerambycidae), from Minas Gerais, Brazil, with new records
Authors: FERREIRA GABRIEL S. , CORRÊA CAIO C. D. , MONNÉ MIGUEL A. , MONNÉ MARCELA L.
Published: February 2024

A new species, Parahephaestion mimicus sp. nov., is described. Two species are newly recorded for the Brazilian state of Minas Gerais: Sphalloeme costipennis Melzer, 1928 (Cerambycinae, Oemini) and Oreodera omissa Melzer, 1932 (Lamiinae, Acrocinini). Six species are new records for the RPPN Sanctuary of Caraça, (Brazil, Minas Gerais): Thalusia atrata (Melzer, 1918) (Cerambycinae, Rhopalophorini), Trachelissa pustulata (Audinet-Serville, 1834) (Cerambycinae, Trachyderini), Ateralphus dejeani (Lane, 1973) (Lamiinae, Acanthoderini), Phacellocera plumicornis (Klug, 1825) (Lamiinae, Anisocerini), Oncideres impluviata (Germar, 1823), and Psyllotoxus griseocinctus Thomson, 1868 (Lamiinae, Onciderini).