bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract B112: Single-cell profiling of neoplastic cell populations in a KRAS-initiated zebrafish pancreatic cancer model
Authors: Matar Somer M. , Goodale Britton C. , Liu Xiaoying , Katanga Annie , Gallien Nicole F. , Blazquez Sandra , Alonso-Curbelo Direna , Leach Steven D.
Published: January 2024

While the majority of human pancreatic cancers are classified as ductal adenocarcinomas, the cell of origin of these tumors remains uncertain and many tumors are comprised of dedifferentiated cell types, making it imperative to understand the full spectrum of neoplastic differentiation and how it is regulated. We have developed a new zebrafish model of pancreatic cancer driven by tissue-specific expression of UAS:mK02-KRASG12D under the regulation of a Ptf1a:Gal4/VP16 transcriptional driver. Transgenic zebrafish generate mixed tumors comprised histologically of mixed acinar and ductal elements, providing the opportunity to interrogate specific transcriptional and epigenetic modifiers responsible for regulating neoplastic pancreatic cellular differentiation. Single-cell RNA sequencing of these tumors has confirmed neoplastic cell populations expressing exclusively acinar and ductal markers, as well as distinct clusters expressing markers of both cell lineages. Screening a panel of 21 unique chromatin modifiers and chromatin readers for differential expression in these distinct cell clusters reveals hdac9b to be upregulated in the progenitor-like ductal population. Gain- and loss-of-function genetic studies will be used to determine the functional role of hdac9b in generating distinct neoplastic cell differentiation states. We are also generating pseudo-time trajectory inferences to further determine the directionality of differentiation states in these cells. By generating new insights into regulation of distinct differentiation states in pancreatic cancer, we hope that new strategies for therapeutic manipulation of neoplastic cell differentiation will emerge.

Citation Format: Somer M. Matar, Britton C. Goodale, Xiaoying Liu, Annie Katanga, Nicole F. Gallien, Sandra Blazquez, Direna Alonso-Curbelo, Steven D. Leach. Single-cell profiling of neoplastic cell populations in a KRAS-initiated zebrafish pancreatic cancer model [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr B112.
Abstract C043: Spatial proteomic immune profiling of pancreatic ductal adenocarcinoma and the tumor microenvironment
Authors: Yeung Jason , Bai Yunhao , Yeo Yao Yu , Qiu Huaying , Zhu Bokai , Heij Lara R. , Shah Enas Abu , Nolan Garry P. , Sivakumar Shivan , Jiang Sizun
Published: January 2024

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with poor prognosis and treatment options. Technological challenges in dissecting the immune constituents of the PDAC tumor microenvironment (TME) has limited our understanding of the complex disease mechanisms in vivo, which may in part explain the lack of novel therapeutics for this recalcitrant disease. Here, we performed spatial proteomics using the multiplexed ion beam imaging (MIBI) approach to quantify 36 spatial signatures in tissues from a cohort of twelve treatment naïve PDAC patients. We applied a deep learning segmentation algorithm to better resolve expression levels at the single cell resolution, and robustly stratify phenotypes through an iterative process of clustering and annotation, with expert visual validation. The combination of phenotypic quantification, functional marker evaluation within the cell types identified, as well as machine-learning based topic modeling to understand cellular neighborhoods, can better explain the cellular and functional components within the intricate PDAC TME. Our analysis revealed markedly lower B and effector T cell infiltration in the treatment-naive TME of patients who eventually relapsed to date following adjuvant chemotherapy. We additionally observed the enrichment of myeloid cell populations, including tumor-associated macrophages and neutrophils, associated with PDAC tumorigenesis and worse prognosis. A deeper analysis of our functional protein expression exhibited the enrichment of GATA3 in regulatory T cells in relapsed patients, a marker which has been associated with increased accumulation and infiltration of Tregs at inflammatory sites. Our study demonstrates the importance of a targeted dissection of the spatially orchestrated immune responses and dysregulation associated with PDAC, and exemplifies how a deeper understanding of the immune and tumor components and functional aspects in situ can help improve our understanding for patients with this disease.

Citation Format: Jason Yeung, Yunhao Bai, Yao Yu Yeo, Huaying Qiu, Bokai Zhu, Lara R. Heij, Enas Abu Shah, Garry P. Nolan, Shivan Sivakumar, Sizun Jiang. Spatial proteomic immune profiling of pancreatic ductal adenocarcinoma and the tumor microenvironment [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C043.
Abstract C056: The initiation and progression of pancreatic ductal adenocarcinoma through a p53 lens
Authors: Hanson Kathryn J. , Minor Allegra C. , Flowers Brittany M. , Kaiser Alyssa M. , Hughes Nicholas , Vogel Hannes , Cong Le , Attardi Laura D.
Published: January 2024

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a 5-year survival rate of only 11%. Slated to be the 2nd most deadly cancer by 2026, pancreatic cancer survival rates have not improved substantially over the years. With a lack of early detection methods and a highly immunosuppressive tumor microenvironment (TME), PDAC tumors are highly resistant to treatment. Oncogenic mutations in KRAS are present in >90% of cases and mutations in the tumor suppressor gene TP53 are present in ~72% of cases. However, why p53 mutations are so prevalent and how they enhance PDAC development is not well understood. To elucidate how exactly p53 loss promotes PDAC, we are using genetically engineered mouse models combined with single-cell and spatial transcriptomic technologies. In this mouse model, PDAC is driven from adult acinar cells with a tamoxifen-inducible Ptf1aCreER allele by oncogenic Kras (KrasG12D) along with either p53 wild type (p53wt) or p53 deficiency (p53flox). In this model, acinar cells can give rise to PDAC likely through a transdifferentiation process called acinar-to-ductal metaplasia (ADM), which leads to pancreatic intraepithelial neoplasias (PanINs) and then PDAC. The initial cell fate transition, ADM, can be activated by growth factors, inflammation, and injury. We have conducted single-cell and spatial transcriptomics to compare early stages of tumor development in the presence and absence of p53, and we will present our latest analyses. Providing insight into the early events of PDAC will lead to new approaches for improving clinical intervention in human PDAC.

Citation Format: Kathryn J. Hanson, Allegra C. Minor, Brittany M. Flowers, Alyssa M. Kaiser, Nicholas Hughes, Hannes Vogel, Le Cong, Laura D. Attardi. The initiation and progression of pancreatic ductal adenocarcinoma through a p53 lens [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C056.
Abstract C079: Targeting cancer stem cell OXPHOS with tailored ruthenium complexes as a new approach to treat pancreatic cancer
Authors: Sainz Bruno Jr , Alcalá Sonia , Villarino Lara , Ruíz-Cañas Laura , Couceiro José , Martínez-Calvo Miguel , Palencia-Campos Adrián , Navarro Diego , Cabezas-Sainz Pablo , Cordero-Barreal Alfonso , Rubiolo Juan A. , González-Páramos Cristina , Carrato Alfredo , Hermann Patrick C. , Sánchez Laura , Torrente Susana , Fernández-Moreno Miguel Ángel , Mascareñas José L.
Published: January 2024

Background and aims: Annual world-wide cancer-related fatalities remain high for pancreatic ductal adenocarcinoma (PDAC), largely due to the presence of “stem-like” tumor cells known as cancer stem cells (CSCs). Previous studies by our group have shown that oxidative phosphorylation (OXPHOS) is the main pathway by which pancreatic CSCs meet their energetic requirements; therefore, OXPHOS represents an Achille’s heel of these highly tumorigenic cells. Methods: The anti-CSC activity of a ruthenium complex featuring bipyridine and terpyridine ligands and one coordination labile position (Ru1) was evaluated across primary PDAC cultures and 8 patient-derived xenografts (PDXs). RNAseq analysis followed by mitochondria-specific molecular assays were used to determine the mechanism of action. Results: We show that Ru1 is capable of inhibiting CSC OXPHOS function in vitro, and more importantly, it presents excellent anti-cancer activity, with low toxicity, across a large panel of PDXs. Mechanistic studies suggest that this activity stems from Ru1 binding to the D-loop region of the mitochondrial DNA of CSCs, inhibiting OXPHOS complex-associated transcription, leading to reduced mitochondrial oxygen consumption, membrane potential, and ATP production, all of which are necessary for PaCSCs that heavily depend on mitochondrial respiration. Conclusion Overall, the coordination complex Ru1 represents not only an exciting new anti-cancer agent, but also a molecular tool to dissect the role of OXPHOS in CSCs. Results indicating that the compound is non-toxic and highly effective in vivo are extremely exciting, and have allowed us to uncover an unprecedented approach to fight PDAC based on targeting CSC OXPHOS.

Citation Format: Bruno Jr Sainz, Sonia Alcalá, Lara Villarino, Laura Ruíz-Cañas, José Couceiro, Miguel Martínez-Calvo, Adrián Palencia-Campos, Diego Navarro, Pablo Cabezas-Sainz, Alfonso Cordero-Barreal, Juan A. Rubiolo, Cristina González-Páramos, Alfredo Carrato, Patrick C. Hermann, Laura Sánchez, Susana Torrente, Miguel Ángel Fernández-Moreno, José L. Mascareñas. Targeting cancer stem cell OXPHOS with tailored ruthenium complexes as a new approach to treat pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C079.
Abstract C082: Decoding the KRAS-dependent proteome through the ribosomal lens
Authors: Singh Kamini , Nguyen Trang Uyen , Pederson Eric Nels , Kumar Vinay , Yun Xiaoling , Ouyang Zhengqing
Published: January 2024

Our study addresses the gap in understanding the KRAS-specific translation landscape and functional proteome in cancer. We demonstrate that mutant KRAS drives distinct mechanisms of translational control to fuel cancer growth. By leveraging ribosome footprinting and advanced sequencing techniques, we investigate the impact of sotorasib, a targeted inhibitor of G12C mutant KRAS activity, on translation. Notably, KRAS (G12C) inhibition profoundly alters the translation of ribosomal proteins and translation elongation factors. Additionally, we reveal that KRAS inhibition resulted in ribosome stalling on a specific subset of mRNAs. Acute treatment with sotorasib hampers the translation of crucial oncogenic proteins, including MYC, as well as proteins involved in metabolism. These translational changes are facilitated by specific RNA motifs and RNA binding proteins that respond to KRAS activity. In essence, our study delineates the KRAS (G12C)-specific regulation of translation and elucidates the mechanism underlying KRAS (G12C)-mediated control over the cancer proteome.

Citation Format: Kamini Singh, Trang Uyen Nguyen, Eric Nels Pederson, Vinay Kumar, Xiaoling Yun, Zhengqing Ouyang. Decoding the KRAS-dependent proteome through the ribosomal lens [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C082.
Further Expanding the Mutational Spectrum of Gorlin Syndrome in Three Unrelated Families
Authors: Kolkiran Abdulkerim , Şimşek-Kiper Pelin Özlem , Topaloğlu Yasan Göknur , Karaosmanoğlu Beren , Taşkıran Ekim , Utine Gülen Eda , Tüz Hakan H. , Boduroğlu Koray
Published: January 2024

Introduction: Gorlin syndrome is a rare, autosomal dominant multi-systemic disorder with a predisposition to the development of cancers such as medulloblastoma and nevoid basal cell carcinoma. Heterozygous pathogenic variants in PTCH1 are responsible for 90% of Gorlin syndrome cases. Pathogenic variants in PTCH1 cause overstimulation of the sonic hedgehog signaling pathway, which plays a role in the development of embryonic structures and tumorigenesis. Clinical major and minor diagnostic criteria for Gorlin syndrome have been determined. Odontogenic keratocyst (OKC) is the most common reason for medical admission in Gorlin syndrome. In this article, it is aimed to draw attention to the fact that patients with Gorlin syndrome are not very rare in our country and the variability in phenotypic and dysmorphic findings may be a clue for the diagnosis. Methods: Exome sequencing was performed on the Illumina NextSeq550 System platform by using the Ion Ampliseq exome RDY kit for Illumina. Sanger sequencing was performed accordingly for the other affected individuals in both families. Results: In this study, the clinical and molecular findings of 9 Gorlin syndrome patients from three unrelated families are presented. Macrocephaly, calcification of falx cerebri, palmar-plantar pits, rib anomalies, and OKC were detected in decreasing order in more than half of the patients. A novel heterozygous frameshift PTCH1 variant in family 1, a nonsense previously reported PTCH1 variant in family 2, and a novel heterozygous splice-site PTCH1 variant in family 3 were detected. Conclusion: Gorlin syndrome should be kept in mind in patients presenting with macrocephaly, palmoplantar pits, and OKC history. Careful examination of all family members is essential in the timely diagnosis of other affected individuals with minor phenotypic findings.
Cardiac Agents during Neonatal Cardiopulmonary Resuscitation
Authors: Ramsie Marwa , Cheung Po-Yin , O’Reilly Megan , Roberts Calum T. , Polglase Graeme R. , Schmölzer Georg M.
Published: January 2024

Background: Epinephrine (adrenaline) is currently the only cardiac agent recommended during neonatal resuscitation. The inability to predict which newborns are at risk of requiring resuscitative efforts at birth has prevented the collection of large, high-quality human data. Summary: Information on the optimal dosage and route of epinephrine administration is extrapolated from neonatal animal studies and human adult and pediatric studies. Adult resuscitation guidelines have previously recommended vasopressin use; however, neonatal studies needed to create guidelines are lacking. A review of the literature demonstrates conflicting results regarding epinephrine efficacy through various routes of access as well as vasopressin during asystolic cardiac arrest in animal models. Vasopressin appears to improve hemodynamic and post-resuscitation outcomes compared to epinephrine in asystolic cardiac arrest animal models. Key Messages: The current neonatal resuscitation guidelines recommend epinephrine be primarily given via the intravenous or intraosseous route, with the endotracheal route as an alternative if these routes are not feasible or unsuccessful. The intravenous or intraosseous dose ranges between 0.01 and 0.03 mg/kg, which should be repeated every 3–5 min during chest compressions. However, the optimal dosing and route of administration of epinephrine remain unknown. There is evidence from adult and pediatric studies that vasopressin might be an alternative to epinephrine; however, the neonatal data are scarce.
Ego- and Geo-Centered References: A Functional Neuroimagery Study
Authors: Saj Arnaud , Honoré Jacques , Borel Liliane
Published: January 2024

Introduction: The integration of vestibular, visual, and somatosensory cues allows the perception of space through the orientation of our body and surrounding objects with respect to gravity. The main goal of this study was to identify the cortical networks recruited during the representation of body midline and the representation of verticality. Methods: Thirty right-handed healthy participants were evaluated using fMRI. Brain networks activated during a subjective straight-ahead (SSA) task were compared to those recruited during a subjective vertical (SV) task. Results: Different patterns of cortical activation were observed, with differential increases in the angular gyrus and left cerebellum posterior lobe during the SSA task, in right rolandic operculum and cerebellum anterior lobe during the SV task. Discussion: The activation of these areas involved in visuo-spatial functions suggests that bodily processes of great complexity are engaged in body representation and vertical perception. Interestingly, the common brain networks involved in SSA and SV tasks were comprised of areas of vestibular projection that receive multisensory information (parieto-occipital areas) and the cerebellum, and reveal a predominance of the right cerebral and cerebellar hemispheres. The outcomes of this first fMRI study designed to unmask common and specific neural mechanisms at work in gravity- or body-referenced tasks pave a new way for the exploration of spatial cognitive impairment in patients with vestibular or cortical disorders.
Krankenhauseinweisungen wegen Asthma und Hitzeexposition in England: eine Fall-Crossover-Studie von 2002 bis 2009
Authors: Konstantinoudis Garyfallos , Minelli Cosetta , Yu Lam Holly Ching , Fuertes Elaine , Ballester Joan , Davies Bethan , Vicedo-Cabrera Ana Maria , Gasparrini Antonio , Blangiardo Marta
Published: January 2024

Hintergrund: Frühere Studien haben einen Zusammenhang zwischen hohen Temperaturen und Krankenhauseinweisungen wegen Asthma festgestellt. Es wurde eine geschlechts- und altersabhängige Anfälligkeit festgestellt. Über die zeitliche Entwicklung dieses Effekts und seine regionale Variation ist jedoch wenig bekannt. Ziel dieser Studie ist es, den Zusammenhang zwischen Asthma-bedingten Krankenhauseinweisungen und warmen Temperaturen zu bewerten und die Anfälligkeit nach Alter, Geschlecht, Zeit und Region zu untersuchen. Methoden: Wir haben individuelle Daten zu Krankenhauseinweisungen wegen Asthma mit hoher zeitlicher (täglich) und regionaler (Postleitzahl) Auflösung für England im Zeitraum 2002 bis 2019 von NHS Digital abgerufen. Die Tagesmitteltemperatur mit einer Auflösung von 1 km × 1 km wurde vom britischen Met Office bezogen. Wir haben uns auf eine Latenzzeit von 0 bis 3 Tagen konzentriert. Wir haben ein Fall-Crossover-Studiendesign verwendet und Bayes’sche hierarchische Poisson-Modelle unter Berücksichtigung möglicher Störfaktoren (Niederschlag, relative Luftfeuchtigkeit, Windgeschwindigkeit und nationale Feiertage) angepasst. Ergebnisse: Nach Berücksichtigung der Störfaktoren fanden wir einen Anstieg des Risikos einer Asthma-bedingten Krankenhauseinweisung um 1,11% (95%-Kredibilitätsintervall: 0,88–1,34%) für jeden Anstieg der sommerlichen Umgebungstemperatur um 1 °C. Der Effekt war bei den 16- bis 64-jährigen Männern (2,10%, 1,59–2,61%) und in den ersten Jahren unserer Analyse am größten. Wir fanden auch Hinweise darauf, dass der Effekt mit der Zeit linear abnimmt. Die Bevölkerung in Yorkshire und dem Humber sowie in den East und West Midlands war am stärksten gefährdet. Schlussfolgerung: Diese Studie liefert Beweise für einen Zusammenhang zwischen hohen Temperaturen und Asthma-bedingten Krankenhauseinweisungen. Der Effekt nahm mit der Zeit ab. Mögliche Erklärungen sind zeitliche Unterschiede in den Mustern der Hitzeexposition, Anpassungsmechanismen, Asthmamanagement, Lebensstil, Komorbiditäten und berufsbedingte Gründe.
To Each His Own Fear: Gender-Related Association of Anxiety, Substance Use, and Eating Disorders in a Representative Birth Cohort Sample of Young Adults with Either COMT Val158Met allele
Authors: Kiive Evelyn , Kurrikoff Triin , Veidebaum Toomas , Harro Jaanus
Published: January 2024

Introduction: The role of catechol-O-methyltransferase (COMT) in catecholamine neurotransmitter metabolism has led to the investigation of variants of the corresponding gene in the etiology of different psychiatric disorders, but the results are inconclusive. Methods: We have examined the relationship between COMT Val158Met single nucleotide polymorphism (rs4680) and the occurrence of psychiatric disorders in a highly representative birth cohort sample of young adults in the Estonian Children Personality Behaviour and Health Study (original n = 1,238). The lifetime occurrence of psychiatric disorders at the age of 25 years was assessed with the Mini-International Neuropsychiatric Interview. Results: Both Val- and Met-alleles of the COMT Val158Met were associated with specific psychiatric disorders. Met-allele carriers had a significantly higher occurrence of agoraphobia (3.2% vs. 0.5%; χ2 = 4.10; p < 0.05) compared to Val/Val homozygotes. Also, the occurrence of panic disorder was significantly higher in female Met-allele carriers than in Val/Val homozygote females (10.2% vs. 3.6%; χ2 = 4.62 p = 0.03). In contrast, the occurrence of generalized anxiety disorder was higher in Val/Val females when compared to Met-allele carriers (12.7% vs. 6.8%; χ2 = 4.16; p = 0.04). Also, female Val/Val homozygotes (15.5%) had a higher occurrence of eating disorders than Met-allele carriers (6.1%) of the COMT Val158Met polymorphism (χ2 = 10.39; p = 0.002). In the whole sample, Met-allele homozygotes had a higher occurrence of alcohol use and substance use disorders than Val-allele carriers (χ2 = 3.62 and 3.68, respectively; p < 0.05). Conclusion: In a regional highly birth cohort representative sample, either COMT rs4680 variant was observed in association with specific psychiatric disorders.
Exploring the Chagas Disease-Stroke “Connection”: Findings from a Large Multicenter Study
Authors: Montanaro Vinícius Viana Abreu , Silva Gisele Sampaio , Oliveira Filho Jamary , Pontes-Neto Octavio Marques , do Carmo Pereira Nunes Maria , Bezerra Rodrigo de Paiva , Sousa de Melo Eduardo , Valenca Patrizia Alves de Andrade Luciana , Alves de Oliveira Junior Wilson , Castro Alves de Meira Fidel , Teixeira Antonio Lucio , Maria de Jesus Oliveira Eleonora , de Freitas Gabriel R.
Published: January 2024

Introduction: Strokes are traditionally attributed to risk factors like aging, hypertension, diabetes, and atherosclerosis. Chagas disease has emerged as an important risk factor for stroke in Latin American. Our study aims at describing the largest cohort of patients with Chagas disease and ischemic stroke and determining variables associated with stroke recurrence and cardioembolic cause. Methods: This study is the result of a national multicenter cohort study conducted in Brazil. The study spanned from January 2009 to December 2016 and involved a comprehensive retrospective analysis of medical records of patients with both Chagas disease and stroke. This cohort comprised 499 individuals from diverse Brazilian regions, focusing on vascular risk factors and the epidemiological variables associated with Chagas disease and stroke. Results: Our findings underscore the significant prevalence of traditional vascular risk factors among Chagas disease patients who had stroke. 81% of patients had hypertension, 56% dyslipidemia, and 25% diabetes. We observed a 29.7% recurrence rate, especially within the cardioembolic subgroup. 56% of the patients had embolic stroke of undetermined source (ESUS). Specific electrocardiography abnormalities were associated with an increased risk of cardioembolic etiology (with three altered results increasing 81 fold the chance of the stroke being of cardioembolic nature). Age emerged as a protective factor (OR: 0.98, 95% confidence interval [CI]: 0.970–0.997) against cardioembolic etiology. Anticoagulation therapy was associated with reduced risk (OR: 0.221, 95% CI 0.104–0.472), highlighting the importance of accurate etiological classification. Conversely, female gender (OR: 1.83, 95% CI: 1.039–3.249) emerged as a significant risk factor for stroke recurrence. Conclusion: This study significantly advances our epidemiological understanding of the intersection between Chagas disease and stroke. It emphasizes the critical need for extensive epidemiological investigations, a deeper comprehension of stroke recurrence determinants, and accurate etiological classification to reduce the ESUS population. Our findings have substantial clinical implications, suggesting the need of control of vascular risk factors and comorbidities and hold promise for improving patient care and reducing the burden of Chagas disease and stroke worldwide.
Mental Health of School-Aged Children Treated with Propranolol or Atenolol for Infantile Hemangioma and Their Parents
Authors: Hermans Mireille M. , Schappin Renske , de Laat Peter C.J. , Mendels Elodie J. , Breur Johannes M.P.J. , Langeveld Hester R. , Raphael Martine F. , de Graaf Marlies , Breugem Corstiaan C. , de Wildt Saskia N. , Okkerse Jolanda M.E. , Pasmans Suzanne G.M.A. , Rietman André B.
Published: January 2024

Background: Infants with infantile hemangioma (IH) have been effectively treated with propranolol or atenolol. Concerns were raised about the mental health of these children at school age, due to central nervous system effects of propranolol and visible nature of IH. Objective: This study aimed to compare the mental health at school age of children treated with propranolol to children treated with atenolol for IHs and their parents. Methods: This two-centered cross-sectional study included children aged ≥6 years and treated with either propranolol or atenolol for IH during infancy. Children’s outcomes were performance-based affect recognition (Dutch version of the Developmental Neuropsychological Assessment-II [NEPSY-II-NL]), parent-reported emotional and behavioral functioning (Child Behavioral Checklist [CBCL]), and health-related quality of life (KIDSCREEN-27). Parents’ outcome was parenting stress (Parenting Stress Questionnaire [OBVL]). Results: Data of 105 children (36 propranolol, 69 atenolol; 6.0–11.8 years) were analyzed. Mental health outcomes did not differ between both β-blocker groups. Although overall functioning was in line with norms, children presented specific problems concerning affect recognition, parent-reported attention, and social quality of life. Parents showed increased physical symptoms, depressive symptoms, and parent-child relationship problems. Conclusion: No difference in mental health at school age was found between children treated with propranolol or atenolol for IH. Although few overall mental health problems were found, specific problems require follow-up. Follow-up of children should be directed toward affect recognition, attention, and social functioning in daily life. Problems reported by parents could be ameliorated by mental health support during and after their infant’s β-blocker treatment.
Causal Relationship between Gut Microbiota and Aneurysm: A Mendelian Randomization Study
Authors: Tan Zhentao , Mao Menghui , Jiang Zhe , Hu Huilin , He Chaojie , Zhai Changlin , Qian Gang
Published: January 2024

Introduction: Observational studies have suggested a possible relationship between gut microbiota (GM) and aneurysm development. However, the nature of this association remains unclear due to the inherent limitations of observational research, such as reverse causation and confounding factors. To address this knowledge deficit, this study aimed to investigate and establish a causal link between GM and aneurysm development. Methods: Summary statistics regarding GM and aneurysms were collected from relevant genome-wide association studies. Two samples were used in mendelian randomization (MR). The principal MR technique utilized was inverse-variance weighting, a technique renowned for producing reliable causal effect estimations. Additional MR methods, including weighted median (WM), MR-Egger, MR-PRESSO, and simple mode methods, were employed to ensure the robustness of the aforementioned association and investigate potential biases. Sensitivity analyses were performed to determine the consistency of the MR findings. Results: Varying associations were observed between specific microbial taxa and the different aneurysms analyzed. A negative correlation was observed between aortic aneurysm (AA) and Lentisphaerae, Lentisphaeria, and Victivallales. Conversely, the genus FamilyXIIIUCG001 exhibited an increased risk association. Regarding abdominal AA, Victivallaceae showed a reduced risk, and Bilophila and Catenibacterium were associated with an increased risk. For thoracic AA, negative and positive correlations were observed with Lentisphaerae and Turicibacter, respectively. Lastly, in the case of cerebral aneurysm (CA), Firmicutes and Haemophilus were associated with a decreased risk, and Lachnoclostridium demonstrated an increased risk of association. Conclusion: Our research has established causal relationships between specific GM components and various aneurysms. The obtained knowledge may aid in the development of microbiome-based interventions and the identification of novel biomarkers for targeted prevention strategies.
Protein Kinase N1 Level Predicts Acute Kidney Injury in Patients Undergoing Cardiac Surgery: A Prospective Cohort Study
Authors: Su Lianjiu , Zhu Fangfang , Zhang Jiahao , Cao Edward Z. , Yang Cheng , Sun Haibing , Jiang Xiaofang , Wang Xiaozhan , Wang Jing , Peng Zhiyong
Published: January 2024

Introduction: The objective of this study was to examine the utility of protein kinase N1 (PKN1) as a biomarker of cardiac surgery-associated AKI (CSA-AKI). Methods: A prospective cohort study of 110 adults undergoing on-pump cardiac surgery was conducted. The associations between post-operative PKN1 and CSA-AKI, AKI severity, need for renal replacement therapy (RRT), duration of AKI, length of ICU stay, and post-operative hospital stay were evaluated. Results: Patients were categorized into three groups according to PKN1 tertiles. The incidence of CSA-AKI in the third tertile was 3.4-fold higher than that in the first. PKN1 was an independent risk factor for CSA-AKI. The discrimination of PKN1 to CSA-AKI assessed by ROC curve indicated that the AUC was 0.70, and the best cutoff was 5.025 ng/mL. This group (>5.025 ng/mL) was more likely to develop CSA-AKI (p < 0.001). The combined AUC of EuroSCORE, aortic cross-clamp time, and PKN1 was 0.82 (p < 0.001). A higher level of PKN1 was related to increased need for RRT, longer duration of AKI, and length of ICU and post-operative hospital stays. Conclusions: PKN1 could be a potential biomarker for the prediction of CSA-AKI. The combination of PKN1, EuroSCORE, and aortic cross-clamp time was likely to predict the occurrence of CSA-AKI.
Efficacy of Fine-Needle Aspiration Cytology in Diagnosing Secretory Carcinoma of Salivary Gland: A Systematic Review and Meta-Analysis
Authors: Kala Pooja Sharma , Gupta Mamta , Thapliyal Naveen
Published: January 2024

Introduction: The diagnosis of salivary gland secretory carcinoma (SC) in fine-needle aspiration specimens is challenging because its low-grade nature makes it difficult to differentiate it from various benign or malignant salivary gland neoplasms. Currently, the gold standard is demonstration of ETV6-NTRK3 fusion gene. However, the decision for ordering this costly molecular testing can be facilitated by the correct recognition of its cytomorphological features. The aim of the review was to determine the accuracy of fine-needle aspiration cytology (FNAC) in diagnosis of salivary gland SC. The secondary objective was to recognize varied cytomorphological patterns, characteristic features of SC and differentiate it from other neoplasms. Methods: PubMed/MEDLINE, Science Direct, Embase, Cochrane review, and PROSPERO databases were searched for studies having the following key search terms: (“secretory carcinoma of salivary gland” OR “mammary analogue secretory carcinoma of salivary gland”) AND (“Cytology” OR “Cytological features” OR “aspirate” OR “cytodiagnosis”) published in the time frame of 2010 to June 2023. Studies reporting cytological features of the salivary gland tumors which were confirmed/diagnosed as SC on molecular investigation, were included in the systematic review. Finally, seventeen studies reporting a total of 45 cases were included in the metanalysis. Results: The sensitivity of the FNAC in diagnosing SC in salivary gland is 27.7% (95% CI: 16.6–42.5%). The LR+ (positive likelihood ratio) was 0.654 (0.344–1.245), LR− (negative likelihood ratio) was 1.023 (0.538–1.946), and diagnostic odds ratio was 0.421 (0.129–1.374). The molecular testing and/or immunohistochemistry performed on cell block increased the diagnostic accuracy. Conclusion: Recognition of subtle cytomorphological patterns, i.e., papillary formation, clusters, and singly dispersed cells along with presence of fine intracytoplasmic vacuolations were the characteristic findings in majority of cases, confirmed with diagnostic molecular profiling. This may be helpful in identification of this rare entity with limited published literature and help in increasing diagnostic accuracy.
O nascimento psicológico e as crises do desenvolvimento no pensamento de Margaret Mahler
Authors: Ribeiro Anna Costa Pinto , Caropreso Fátima Siqueira
Published: January 2024

O presente artigo tem como objetivo apresentar a teoria do desenvolvimento precoce da pediatra e psicanalista húngara Margareth Mahler, dando um maior enfoque às crises inerentes ao desenvolvimento, ou seja, às manifestações naturalmente perturbadoras vividas pelo bebê e pelo toddler, ao longo dos trinta e seis primeiros meses de vida. Mahler argumenta que, quando estas fases de alteração do equilíbrio não são satisfatoriamente neutralizadas, podem surgir neuroses infantis precoces, reconhecidas como respostas exacerbadas e rígidas, defensivas e ambivalentes na relação com o objeto de amor. Com este estudo, pretendemos contribuir para a ampliação do conhecimento acerca da primeira infância, em particular, para a elucidação dos impactos psíquicos de desequilíbrios naturais do desenvolvimento psíquico precoce.
Sublimação, angústia e violência no cenário do sofrimento psíquico contemporâneo
Authors: Loffredo Ana Maria
Published: January 2024

No cenário  das expressões do sofrimento psíquico contemporâneo, os atos terroristas   são recortados como veículos privilegiados da violência urbana, sendo examinados  no campo de operação da sublimação, em sua relação com a angústia e com a pulsão de morte, no âmbito da sublimação da agressividade. Impõem-se uma peculiaridade essencial da ocorrência terrorista: seu estatuto de espetáculo, em seu atravessamento pela mídia, destacando-se sua repercussão eminentemente visual. Como a pulsão de saber é tributária de duas pulsões parciais, a pulsão escopofílica e a pulsão de dominação, a exposição recorrente ao fascínio de “ver” remete à capacidade de pensar, potencializando-se a operação de uma das vertentes do arcaico, mais facilmente reativada nessas circunstâncias.
Simulation of a liquid propellant rocket engine manufacturing assembly line utilizing the PFS/PN methodology
Authors: Ferrer Eduardo Seiji Suguimoto Miyazato , Santos Jhonatan Ribeiro dos
Published: January 2024

The system addressed in this paper pertains to an assembly line for liquid propellant rocket engines equipped with turbopump. The challenge involves automating the process of metal 3D printing for the turbopump and combustion chamber, followed by heat treatment for stress relief, X-ray computed tomography inspection, and the subsequent movement of components throughout the factory. To achieve this, the PFS/PN methodology was employed to facilitate a detailed analysis of the system, ensuring control over its inputs and outputs. The system was simulated using the ProModel Discrete Event Simulator, and the results were scrutinized, indicating the robustness of the simulation. Following the Ladder methodology, programming for Programmable Logic Controllers was also developed.
Social Media, Fake News and Covid-19 Vaccine Hesitancy in Zimbabwe
Authors: Chiweshe Manase Kudzai , Dandah Gerald
Published: January 2024

This exploratory paper uses online ethnography to analyse how fake news on social media shaped perceptions and cognitions about Covid-19 vaccines in Zimbabwe. It explores the emergence of social media as an important space for instilling vaccine hesitancy in the context of Covid-19. The paper focuses on how memes, jokes, fake news stories and reports that were shared and consumed on platforms such as WhatsApp, Facebook, Twitter, and YouTube shaped the health-seeking behaviour of people in the context of Covid vaccines in Zimbabwe. The findings show that most people do not trust the government or health institutions. This distrust means they turn to unofficial online sources of information that fuel myths, conspiracies, rumours and gossip and cause fear, panic and vaccine hesitancy. Most citizens resorted to social media to update each other on the efficacy of vaccines and the pros and cons of getting inoculated, highlighting the scepticism surrounding Covid-19 vaccines in Zimbabwe.
Public Health and Political Governance
Authors: Ajiola Felix Oludare
Published: January 2024

In the light of the Covid-19 pandemic, its mutations, concealment by people and the resistance to vaccines against it, it is relevant to examine the outbreak of bubonic plague in colonial Lagos during the early twentieth century and the response by the British colonial authorities. The methodology applied to this study is historical, drawing information from medical, sanitary, land use and physical planning documents accessed from various archives as well as some secondary sources. It is clear that the colonial government’s housing and public health regulations, which allowed authorities to inspect people’s homes for cases of infectious disease, drove people to escape into the hinterland, increasing the spread of the plague. Consequently, the colonial authorities carried out a massive structural and physical reorganisation of towns and villages. They also embarked on large-scale land reclamation, decongested overcrowded houses and introduced sanitary measures to make the environment more habitable. This paper argues that through effective political governance structures the colonial government strategically eliminated the bubonic plague in Lagos.
Multinational Joint Task Force: Lessons for Comprehensive Regional Approaches to Cross-Border Conflict in Africa
Authors: Aniekwe Chika Charles , Brooks Katharine
Published: January 2024

The recent proliferation of cross-border conflicts in Africa has led to the establishment of multiple Ad Hoc Security Initiatives (asi s) on the continent. However, the effectiveness of these initiatives has varied considerably. As such, there is now increased academic and policy interest in the Multinational Joint Task Force (mnjtf), which has seen substantial operational success over the course of its mandate. This paper seeks to contribute to the debate on the strengths and weaknesses of the mnjtf model and the effectiveness of the Force in the Lake Chad region through an exploration of the mnjtf from an internal perspective. The authors of this paper have both worked closely with the mnjtf in recent years and the paper is based upon interviews with current and former mnjtf personnel, staff of the Lake Chad Basin Commission (which oversees the mnjtf) as well as donor and UN partners. In exploring this internal perspective, the article undertakes an in-depth examination of the mnjtf, including the relationship between the headquarters and the sectors, and assesses the impact the mnjtf has had upon the Troop Contributing Countries (tcc s). It identifies areas where the mnjtf has become a regional hub of best practice, challenges that have compromised its effectiveness, and the impact of military diplomacy on the security of the region. Finally, it concludes by drawing lessons from this experience for other conflicts requiring a comprehensive regional and international response.
The Representation of Women in African-Led Peace Support Operations
Authors: Olaitan Zainab Monisola
Published: January 2024

The discourse on the evolving nature of African-led peace support operations (pso) is not complete without asking how gender-inclusive they are. Women have historically been underrepresented within the peace and security space. While several interventions have been made to ensure that pso s on the continent become better, the same cannot be said for gender inclusion. This article examines the participation of women in African-led pso s. It draws on Rwanda as a case study to contextualize the discourse on how gender inclusive African police and troops contributing countries (p/tcc s) are. The analysis finds that efforts at improving pso s on the African continent have not translated into increased representation of women. In particular, African p/tcc s are yet to ensure a considerable number of women in their deployments. The article recommends that there needs to be concerted effort by African p/tcc s and other regional organizations to ensure gender-inclusivity in African-led pso s.
A new genus and species in the tribe Penthimiini (Hemiptera: Cicadellidae: Deltocephalinae) with a key to genera of the tribe from China
Authors: WANG DONGMING , ZHANG YALIN
Published: January 2024

A new leafhopper genus, Tenuicapitis gen. nov. with type species T. xizangensis sp. nov. from China is described and illustrated. A key to genera of the tribe Penthimiini from China is provided.
Thirty-four new species of Rhagovelia (Heteroptera: Veliidae) from the East Papua Composite Terrane, far eastern New Guinea
Authors: POLHEMUS DAN A.
Published: January 2024

Thirty-four new species of Rhagovelia are described from the East Papua Composite Terrane of far eastern New Guinea. The new taxa described from this area are as follows: R. yela, R. woa, and R. mbo from Rossel Island; R. tagula, R. kolukolu, and R. riu from Tagula Island; R. bwagabwaga from Misima Island; R. suloga from Woodlark Island; R. torrenticola and R. elongata from Goodenough Island; R. awaetowa from Fergusson Island; R. dibuwa from Normanby Island; R. basima from Fergusson and Normanby islands; R. kalawai from Sideia and Basilaki islands; R. guiagoila from Basilaki, Sideia and Sariba islands; R. tufi, R. bowutu, R. obscura, R. upalai, R. antap, R. goilala, R. udabe, R. watuti, R. peninsularis, R. auga, R. aviavi, R. tekadu, R. sapoi, R. mimani, R. dinga, R. ivimkana, R. loriae, R. grisea, and R. cheesmanae from the Owen Stanley Range of eastern New Guinea. Redescriptions are also provided for five previously described species occurring in this portion of New Guinea: R. peggiae Kirkaldy, R. hirsuta Lansbury, R. priori Lansbury, R. caesius Lansbury and R. aureospicata Lansbury. A regional key is provided for these 39 species of Rhagovelia occurring in the Papuan Peninsula and adjacent island groups, accompanied by figures of the male parameres and other diagnostic morphological structures, and distribution maps for all species.
1. Whitman on the Bible
Authors: Dobbs-Allsopp F. W.
Published: January 2024

The chapter provides a preliminary brief for Whitman’s familiarity with the Bible. While there is a longstanding consensus among Whitman scholars on this issue, it nevertheless seems appropriate to begin with the “massing of evidence” called for by M. N. Posey. The ensuing survey is somewhat eclectic (e.g., connecting Whitman with known or currently extant bibles) but it focuses in the main on Whitman’s own meta-discourse about the Bible and features an extended look at his late and under-appreciated essay, “The Bible as Poetry” (1883). In particular, I seek to discern what of the sentiments expressed about the Bible in this essay (e.g., Whitman’s awareness of the lack of rhyme in biblical poetry) may be traced back to the germinal period of Leaves’ inception. In the process, I begin identifying aspects of Whitman’s style that may be indebted (to varying degrees) to the Bible (e.g., his preference for lyric). I close the chapter by spotlighting the coincidence of Whitman’s breaking into free verse in 1850 while writing three biblically inflected poems. And though I do not elaborate on this free verse or Whitman’s proclivity for the lyric, that both offer substantial links to the Bible should not go unnoticed. Whitman collages all manner of language material, especially those aspects of form and structure that are not oversaturated with semantic uptake.
4. Parallelism
Authors: Dobbs-Allsopp F. W.
Published: January 2024

Galway Kinnell observes that Whitman is “the greatest virtuoso of parallel structure in English poetry.” G. W. Allen’s early essay, “Biblical Analogies,” successfully establishes the presence and significance of parallelism in Whitman, especially as it bears upon the poet’s underlying prosody, and the likelihood that the Bible is an important source of Whitman’s knowledge of parallelism. In that analysis, parallelism is understood primarily through Robert Lowth’s biblical paradigm. Unfortunately, that paradigm was already much belated in 1933, then a full 180 years after Lowth’s initial exposition of it. Moreover, Allen’s own explication of the paradigm—mediated at second- and third-hand—is flawed in various ways. And compounding these problems is the fact that the understanding of parallelism in Whitman scholarship more broadly appears to be essentially that of Allen (with a few exceptions), and thus is dated and shot through with problematic assumptions. The overriding ambition of this chapter, then, is to re-situate the study of parallelism in Whitman. The initial part of the chapter is dedicated to explicating Lowth’s paradigm and its critical reception in modern biblical scholarship. This is done because of the foundational role which the biblical paradigm has played in Whitman scholarship and because Hebrew Bible is one of the few disciplines of textual study where parallelism as a literary phenomenon has been robustly theorized. The analytics of parallelism, regardless of its originating textual source, is portable, as Allen rightly perceived. The main body of the chapter, building on the foregoing overview, seeks to discern more precisely what may have devolved from the Bible in Whitman’s understanding and use of parallelism. The final section of the chapter features exploratory observations about how Whitman moves beyond the biblical paradigm he inherits and molds parallelism to suit his own poetic ends.
Microstructure and field electron emission properties of boron doped diamond films
Authors: Zou Y S , Li Z X , Yang H
Published: January 2024

Boron doping into diamond film can improve its conductivity and enhance its applications in electronic device, electrochemical and biomedical sensing devices. In the present study, boron doped diamond films were deposited on Si(100) using trimethylboron as a boron source by microwave plasma chemical vapour deposition with the B/C ratio in the gas mixture varying from 0 to 11 000 ppm. The boron doping resulted in the reduction in grain size of diamond and the increase in crystal imperfection. The number of twins in diamond grains increased for boron doped diamond films deposited at a high B/C ratio. Two new peaks at approximately 500 and 1220 cm−1 resulted from Fano interference in Raman spectra were observed and dominated for heavily boron doped diamond film. Boron doping into diamond films improved their field electron emission properties and remarkably reduced the turn-on electric field. The low turn-on electric field of 15·3 V μm−1 was achieved for boron doped diamond film deposited at B/C = 5600 ppm.