bluuebunny/crossref_metadata_2025 huggingface dataset:
Extracellular Vesicles Containing circMYBL1 Induce CD44 in Adenoid Cystic Carcinoma Cells and Pulmonary Endothelial Cells to Promote Lung Metastasis
Authors: Fu Min , Gao Qian , Xiao Mian , Li Rui-Feng , Sun Xin-Yi , Li Sheng-Lin , Peng Xin , Ge Xi-Yuan
Published: April 2024

Adenoid cystic carcinoma (ACC) is a rare malignant epithelial neoplasm that arises in secretory glands and commonly metastasizes to the lungs. MYBL1 is frequently overexpressed in ACC and has been suggested to be a driver of the disease. In this study, we identified a circular RNA (circRNA) derived from MYBL1 pre-mRNA that was accompanied by the overexpression of MYBL1 in ACC. Overexpression of circMYBL1 was correlated with increased lung metastasis and poor overall survival in patients with ACC. Ectopic circMYBL1 overexpression promoted malignant phenotypes and lung metastasis of ACC cells. Mechanistically, circMYBL1 formed a circRNA–protein complex with CCAAT enhancer–binding protein β (CEBPB), which inhibited ubiquitin-mediated degradation and promoted nuclear translocation of CEBPB. In the nucleus, circMYBL1 increased the binding of CEBPB to the CD44 promoter region and enhanced its transcription. In addition, circMYBL1 was enriched in small extracellular vesicles (sEV) isolated from the plasma of patients with ACC. Treatment with sEVs containing circMYBL1 in sEVs enhanced prometastatic phenotypes of ACC cells, elevated the expression of CD44 in human pulmonary microvascular endothelial cells (HPMEC), and enhanced the adhesion between HPMECs and ACC cells. Moreover, circMYBL1 encapsulated in sEVs increased the arrest of circulating ACC cells in the lung and enhanced lung metastatic burden. These data suggest that circMYBL1 is a tumor-promoting circRNA that could serve as a potential biomarker and therapeutic target for ACC.

Significance: circMYBL1 stabilizes CEBPB and upregulates CD44 to promote adhesion between cancer cells and endothelial cells and enables lung metastasis of adenoid cystic carcinoma, suggesting that inhibition of this axis could improve patient outcomes.
Figure S7 from Epithelial Expressed B7-H4 Drives Differential Immunotherapy Response in Murine and Human Breast Cancer
Authors: Wescott Elizabeth C. , Sun Xiaopeng , Gonzalez-Ericsson Paula , Hanna Ann , Taylor Brandie C. , Sanchez Violeta , Bronzini Juliana , Opalenik Susan R. , Sanders Melinda E. , Wulfkuhle Julia , Gallagher Rosa I. , Gomez Henry , Isaacs Claudine , Bharti Vijaya , Wilson John T. , Ballinger Tarah J. , Santa-Maria Cesar A. , Shah Payal D. , Dees Elizabeth C. , Lehmann Brian D. , Abramson Vandana G. , Hirst Gillian L. , Brown Swigart Lamorna , van ˈt Veer Laura J. , Esserman Laura J. , Petricoin Emanuel F. , Pietenpol Jennifer A. , Balko Justin M.
Published: April 2024

Supplemental Figure 7. B7-H4 and PD-L1 are not mutually exclusive on tumor cells. Data shown are reverse phase protein array expression data of B7-H4 and PD-L1 (SP142, 22C3, or Atezolizumab) from the I-SPY2 patient cohort. Samples were a mixture of TNBC and ER+ tumors and were treated with chemotherapy ± anti-PD-1. Depending on the antibody clone selected to detect PD-L1 expression, B7-H4 had no correlation, or a positive correlation to PD-L1 expression in these tumors. Data analyzed by spearman correlation and shown with linear regression best-fit line. n = 151 patients.
Figure S4 from Epithelial Expressed B7-H4 Drives Differential Immunotherapy Response in Murine and Human Breast Cancer
Authors: Wescott Elizabeth C. , Sun Xiaopeng , Gonzalez-Ericsson Paula , Hanna Ann , Taylor Brandie C. , Sanchez Violeta , Bronzini Juliana , Opalenik Susan R. , Sanders Melinda E. , Wulfkuhle Julia , Gallagher Rosa I. , Gomez Henry , Isaacs Claudine , Bharti Vijaya , Wilson John T. , Ballinger Tarah J. , Santa-Maria Cesar A. , Shah Payal D. , Dees Elizabeth C. , Lehmann Brian D. , Abramson Vandana G. , Hirst Gillian L. , Brown Swigart Lamorna , van ˈt Veer Laura J. , Esserman Laura J. , Petricoin Emanuel F. , Pietenpol Jennifer A. , Balko Justin M.
Published: April 2024

Supplemental Figure 4. B7-H4 expression did not change quantity of infiltrating tumor immune cells in vivo regardless of anti-PD-L1 treatment. Untreated and anti-PD-L1 treated EMT6 tumors ± B7-H4 were dissociated to single cell suspension and subjected to flow cytometry with a 14 (for myeloid cells) or 17 (for T cells) color panel on a CyTEK Aurora. n = 3/group for control and 8/group for treated samples. Data were analyzed by One-way ANOVA with Sidak’s post-hoc test for multiple comparisons between the EMT6 control anti-PD-L1 and EMT6 B7-H4+ anti-PD-L1 treatment groups. One-way ANOVA was not significant between groups. Data were analyzed in GraphPad Prism v10.
Figure S3 from Epithelial Expressed B7-H4 Drives Differential Immunotherapy Response in Murine and Human Breast Cancer
Authors: Wescott Elizabeth C. , Sun Xiaopeng , Gonzalez-Ericsson Paula , Hanna Ann , Taylor Brandie C. , Sanchez Violeta , Bronzini Juliana , Opalenik Susan R. , Sanders Melinda E. , Wulfkuhle Julia , Gallagher Rosa I. , Gomez Henry , Isaacs Claudine , Bharti Vijaya , Wilson John T. , Ballinger Tarah J. , Santa-Maria Cesar A. , Shah Payal D. , Dees Elizabeth C. , Lehmann Brian D. , Abramson Vandana G. , Hirst Gillian L. , Brown Swigart Lamorna , van ˈt Veer Laura J. , Esserman Laura J. , Petricoin Emanuel F. , Pietenpol Jennifer A. , Balko Justin M.
Published: April 2024

Supplemental Figure 3. B7-H4 was expressed on some tissue immune cells in the C57BL/6 model, but not the BALB/c model. (A) Formalin-fixed, paraffin-embedded sections of BALB/c and C57BL/6 mice were stained for B7-H4, CD45, and DAPI using multiplexed immunofluorescence, or B7-H4 by IHC. CD45+ B7-H4+ cells were observed in spleen and intestine in C57BL/6 mice but not BALB/c mice. (B) Based on morphological characterization, these are likely macrophages. BALB/c spleen, intestine, and other healthy tissues examined (lymph node, fat pad, lung) had no B7-H4+ immune cells. Scale bar 20µm. (C) Flow cytometry of B7-H4+ cells are not present in the BALB/c spleen but are in the C57BL/6 spleen, similar to our findings by mIF. (D) Representation of flow cytometry scatter plots. B7-H4+ immune cells were only found in the C57BL/6 spleen, not bone marrow (b.m.)
Figure S2 from Epithelial Expressed B7-H4 Drives Differential Immunotherapy Response in Murine and Human Breast Cancer
Authors: Wescott Elizabeth C. , Sun Xiaopeng , Gonzalez-Ericsson Paula , Hanna Ann , Taylor Brandie C. , Sanchez Violeta , Bronzini Juliana , Opalenik Susan R. , Sanders Melinda E. , Wulfkuhle Julia , Gallagher Rosa I. , Gomez Henry , Isaacs Claudine , Bharti Vijaya , Wilson John T. , Ballinger Tarah J. , Santa-Maria Cesar A. , Shah Payal D. , Dees Elizabeth C. , Lehmann Brian D. , Abramson Vandana G. , Hirst Gillian L. , Brown Swigart Lamorna , van ˈt Veer Laura J. , Esserman Laura J. , Petricoin Emanuel F. , Pietenpol Jennifer A. , Balko Justin M.
Published: April 2024

Supplemental Figure 2. B7-H4 expression is not affected by type I or II interferon or TGF-β treatment in vitro. MMTV-neu epithelial cells that have high levels of endogenous B7-H4 were treated for 72 hours with IFNα or IFNγ at 100ng/mL. B7-H4 expression was analyzed by flow cytometry (n=4-5 per group). Similarly, B7-H4 expression was not altered by TGF-β expression (10 ng/mL) in vitro after 72 hours. Data were analyzed by One-way ANOVA or unpaired t-test.
FIGURE 3 from Epithelial Expressed B7-H4 Drives Differential Immunotherapy Response in Murine and Human Breast Cancer
Authors: Wescott Elizabeth C. , Sun Xiaopeng , Gonzalez-Ericsson Paula , Hanna Ann , Taylor Brandie C. , Sanchez Violeta , Bronzini Juliana , Opalenik Susan R. , Sanders Melinda E. , Wulfkuhle Julia , Gallagher Rosa I. , Gomez Henry , Isaacs Claudine , Bharti Vijaya , Wilson John T. , Ballinger Tarah J. , Santa-Maria Cesar A. , Shah Payal D. , Dees Elizabeth C. , Lehmann Brian D. , Abramson Vandana G. , Hirst Gillian L. , Brown Swigart Lamorna , van ˈt Veer Laura J. , Esserman Laura J. , Petricoin Emanuel F. , Pietenpol Jennifer A. , Balko Justin M.
Published: April 2024

B7-H4 expression is regulated by PI3K signaling. A, Spearman correlations in protein expression from RPPA data collected from patients from the ISPY2 trial. Key positive correlations are called out in blue and key negative correlations are called out in red. B, RPPA data show strong positive correlations between B7-H4 and AKT (pAKT-Ser 473) and strong negative correlations between B7-H4 and PTEN (Ser 380) regardless of tumor hormone receptor status. C, PI3K inhibitor (buparlisib) treatment for 72 hours robustly decreases B7-H4 expression in human MDA-MB-468 breast cancer cells, while MEK inhibitor (trametinib) has no effect. D, Likewise, in MMTV-neu cells, buparlisib reduces B7-H4 expression in dose-dependent manner after 72 hours. Data were analyzed by one-way ANOVA with Dunnet post hoc test for multiple comparisons, P < 0.0001 and P = 0.0005).
FIGURE 2 from Epithelial Expressed B7-H4 Drives Differential Immunotherapy Response in Murine and Human Breast Cancer
Authors: Wescott Elizabeth C. , Sun Xiaopeng , Gonzalez-Ericsson Paula , Hanna Ann , Taylor Brandie C. , Sanchez Violeta , Bronzini Juliana , Opalenik Susan R. , Sanders Melinda E. , Wulfkuhle Julia , Gallagher Rosa I. , Gomez Henry , Isaacs Claudine , Bharti Vijaya , Wilson John T. , Ballinger Tarah J. , Santa-Maria Cesar A. , Shah Payal D. , Dees Elizabeth C. , Lehmann Brian D. , Abramson Vandana G. , Hirst Gillian L. , Brown Swigart Lamorna , van ˈt Veer Laura J. , Esserman Laura J. , Petricoin Emanuel F. , Pietenpol Jennifer A. , Balko Justin M.
Published: April 2024

B7-H4 (VTCN1) is highly correlated with epithelial gene markers in mouse and human cells unlike other checkpoint ligands. A, In human breast cancer cell lines (CCLE), B7-H4 is the only checkpoint ligand positively correlated with epithelial markers and negatively correlated with mesenchymal markers. Data shown are Spearman correlations between genes. Significant correlations (P < 0.05) are indicated by asterisk. B, Genes downregulated during EMT are positively correlated with VTCN1 in human cell lines (CCLE). C, Murine cancer cell lines express B7-H4. D, B7-H4 is only expressed on epithelial EpCAM+ cells in murine and human cells. E, The MMTV-neu cell line with highest B7-H4 levels is comprised of phenotypically epithelial-like (abbreviated E) and mesenchymal-like (M) cells. F, In MMTV-neu cells, the CD44+ M cells do not express B7-H4 but all the EpCAM+ E cells do. G, MMTV-neu E and M cells express hallmark markers. H, Single-cell RNA sequencing of the heterogenous MMTV-neu cells confirms Vtcn1 is solely expressed in the epithelial cell population. I, A cohort of human tumors including both TNBC and ER+HER2− were stained for B7-H4, EpCAM, and CD44 by mIF. Data shown are log2 of % B7-H4+ tumor cells and include 132 samples with >1% B7-H4 expression (paired t test of transformed data).
Continuous Fetal Cardiac Monitoring during Fetoscopic Myelomeningocele Repair and Relationship to Spectral Doppler Changes
Authors: Eyerly-Webb Stephanie A. , Howley Lisa , Brock Clifton O. , Lillegard Joseph B. , Fisher James , Reynolds Benjamin , Barthel Emily F. , Dion Eric , Snowise Saul
Published: April 2024

Introduction: No evidence-based protocols exist for fetal cardiac monitoring during fetoscopic myelomeningocele (fMMC) repair and intraprocedural spectral Doppler data are limited. We determined the feasibility of continuous fetal echocardiography during fMMC repair and correlated Doppler changes with qualitative fetal cardiac function during each phase of fMMC repair. Methods: Patients undergoing fMMC repair had continuous fetal echocardiography interpreted in real-time by pediatric cardiology. Fetal data included fetal heart rate (FHR), qualitative cardiac function, mitral and tricuspid valve inflow waveforms, and umbilical artery (UA), umbilical vein (UV), ductus arteriosus (DA), and ductus venosus (DV) Dopplers. Results: UA abnormalities were noted in 14/25 patients, UV abnormalities were observed in 2 patients, and DV and DA abnormalities were each noted in 4 patients. Qualitative cardiac function was normal for all patients with the exception of one with isolated left ventricular dysfunction during myofascial flap creation, concurrent with an abnormal UA flow pattern. All abnormalities resolved by the first postoperative day. Conclusions: Continuous fetal echocardiography was feasible during all fMMC repairs. Spectral Doppler changes in the UA were common during fMMC procedures but qualitative cardiac dysfunction was rare. Abnormalities in the UV, DV, and DA Dopplers, FHR, and cardiac function were less common findings.
Determination of the Frequency of BCL-2 Polymorphisms (c.-717C>A and c.*2364G>A) and LIF Polymorphism (c.*1414T>G) in Patients with Congenital Anomalies of the Kidney and Urinary Tract
Authors: Oztepe Tugce , Sahin Feride Iffet , Caltik Yilmaz Aysun , Baskin Esra , Haberal Mehmet , Terzi Yunus Kasim
Published: April 2024

Introduction: Congenital anomalies of the kidney and urinary tract (CAKUT) are characterized by several malformations. Its prevalence is 0.3–0.6% in live births. The B-cell lymphoma (BCL-2) gene regulates apoptosis, and the Leukemia Inhibitory Factor (LIF) gene plays a role in many biological processes, such as blastocyst growth and uterine preparation for implantation. In this study, two single nucleotide polymorphisms (SNPs) of the BCL-2 gene (rs2279115 and rs4987856) and one SNP of the LIF gene (rs929271) were investigated in CAKUT patients for the first time. Methods: Hundred and twenty-nine CAKUT patients and 105 controls were enrolled in this study. We used polymerase chain reaction-restriction fragment length polymorphism for rs2279115 and rs929271 and SNaPshot for rs4987856. The χ2 test was used to compare discrete variables, and the independent sample t test was used to compare continuous variables. Results: The allele frequencies for the rs2279115 and rs4987856 polymorphisms of BCL-2 and the rs929271 polymorphism of LIF were not significantly different between the patient and control groups (p = 0.162, p = 0.053, p = 0.635, respectively). However, the co-segregation analysis revealed a significant difference in the distribution of allele frequencies between the patient and control groups for two genetic variations: LIF rs929271 SNP and BCL-2 rs4987856 SNP (p = 0.034). The relative odds ratio was 2.444 (95% Confidence Interval (CI) 1.054–5.671). Conclusion: This study, which is the first time in the literature, showed that changes in BCL-2 and LIF genes are associated with CAKUT disease.
Feasibility and Safety of Percutaneous Kidney Biopsy in Small Kidneys: Breaking the Paradigm
Authors: Zepeda-Quiroz Ivan , Juarez-Villa Daniel , Gomez-Johnson Víctor Hugo , Sanchez-Vazquez Omar Humberto , Toledo-Ramirez Sebastian Eduardo , Rodriguez-Castellanos Francisco Eugenio , Cortez-Flores Brenda Guadalupe , Garcia-Rivera Alejandro , Madero Rovalo Magdalena , Moguel-Gonzalez Bernardo
Published: April 2024

Introduction: The percutaneous kidney biopsy (PKB) is an essential tool in nephrology; small kidney size has been a relative contraindication to PKB and there is limited data on the safety and utility of performing PKB in this setting. Our aim was to describe the complications of PKB in small kidneys and to assess if kidney biopsy results have an impact on medical decisions and outcomes. Methods: This was a retrospective, descriptive, and observational study. Patients older than 16 years of age with a decreased kidney size (≤8 cm) and undergoing PKB of native kidneys from July 2019 to December 2022 were included. Results: Twenty-five patients were included, 19 women and 6 men. The mean age was 42.3 ± 18.04. The mean kidney length was 7.56 ± 0.33 and the mean width was 4.2 cm. All patients received only 1 puncture, obtaining an average of 12 glomeruli. The mean blood urea nitrogen and serum creatinine were 36 mg/dL and 1.94 mg/dL, respectively and the mean Hgb (hemoglobin) was 12.87 ± 2.81 g/dL. Minor complications occurred in 5 patients, perirenal hematoma in 3 patients, hematuria in 1 patient, and hematoma plus hematuria in 1 patient. Histological examination showed FSGS, lupus nephritis, other Glomerular disease, crescentic glomerulonephritis, and tubulointerstitial nephritis in 36%, 20%, 16%, 16%, and 12% of the cases, respectively. Biopsy resulted in management modification in 64% of cases. In a bivariate analysis, kidney size was not associated with higher complication rates. Conclusions: PKB in small kidneys is a feasible and safe procedure when properly planned, providing an adequate sample in all cases, with an insignificant number of minor complications, and that is clinically relevant.
Extended-Release Calcifediol: A Data Journey from Phase 3 Studies to Real-World Evidence Highlights the Importance of Early Treatment of Secondary Hyperparathyroidism
Authors: Merante Domenico , Schou Henrik , Morin Isabelle , Manu Marius , Ashfaq Akhtar , Bishop Charles , Strugnell Stephen
Published: April 2024

Background: Early secondary hyperparathyroidism (SHPT) diagnosis and treatment are crucial to delay the progression of SHPT and related complications, in particular, cardiovascular events and bone fractures. Extended-release calcifediol (ERC) has been developed for the treatment of SHPT in patients with stage 3/4 chronic kidney disease (CKD) and vitamin D insufficiency (VDI). Summary: This review compares baseline characteristics and treatment responses of SHPT patients receiving ERC in phase 3 studies with those treated with ERC in a real-world study. Mean ± standard deviation baseline parathyroid hormone (PTH) levels were 147 ± 56 pg/mL and 148 ± 64 pg/mL in the phase 3 ERC cohorts, and 181 ± 98 pg/mL in the real-world study. Other baseline laboratory parameters were consistent between the clinical and real-world studies. ERC treatment increased 25-hydroxyvitamin D (25(OH)D) and significantly reduced PTH levels, regardless of baseline CKD stage, in all studies. In the pooled phase 3 per-protocol populations, 74% of the ERC cohort were uptitrated to 60 μg/day after 12 weeks at 30 μg/day, 97% attained 25(OH)D levels ≥30 ng/mL, and 40% achieved ≥30% PTH reduction. Despite a much lower rate of uptitration in the real-world study, 70% of patients achieved 25(OH)D levels ≥30 ng/mL, and 40% had a ≥30% reduction in PTH. Key Messages: These data establish a “continuum” of clinical and real-world evidence of ERC effectiveness for treating SHPT, irrespective of CKD stage, baseline PTH levels, and ERC dose. This evidence supports early treatment initiation with ERC, following diagnosis of SHPT, VDI, and stage 3 CKD, to delay SHPT progression.
A review of the tribe Oestrophasiini Brauer e Bergenstamm (Diptera, Tachinidae)
Authors: Guimarães J. H.
Published: April 2024

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Two new small species of Amphisbaena from the fossil dune field of the middle Rio São Francisco, State of Bahia, Brasil (Reptilia, Amphisbaenia)
Authors: Vanzolini P. E.
Published: April 2024

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O papel paradoxal de Lactobacillus na saúde
Authors: Silva Mariana Araujo Mendes , Leão Mariella Vieira Pereira
Published: April 2024

The genus Lactobacillus is part of the normal microbiota, but is related to a variety of human infections, such as dental abscesses, bacteremia, cholecystitis, empyema, endocarditis, meningitis, peritonitis, prosthetic knee infection and pyelonephritis. Paradoxically, there is evidence of the effectiveness of using Lactobacillus in the form of probiotics for the prevention and treatment of diarrheal and inflammatory intestinal diseases, bacterial vaginosis, urinary and respiratory tract infections and even tooth decay. The present work aimed to demonstrate and discuss these contradictory roles of the genus Lactobacillus. For this, case reports, clinical trials, literature reviews and meta-analyses from the last 30 years were selected, using the keywords: Lactobacillus, Probiotics, Dental Caries, Diseases and Health. Different studies have demonstrated that the effects of probiotics can be specific to each strain and that the most effective strain for each clinical condition, its ideal dose, best form of administration and best time of use are still questionable. Furthermore, the existence of a pre-existing comorbidity or susceptible condition in the patient increases the risk of lactobacilli infections. Thus, it was concluded that, only after a careful investigation of the Lactobacillus strain and the patient, their oral and general conditions, probiotics containing these microorganisms could be used in a safer, more beneficial and more effective way.
Beonquiectasias por corpo extranho: cura pela lobectomia: (considerações sobre um caso)
Authors: Tranchesi João , Fujioka Toshiyasu , Fernandes José Leite
Published: April 2024

Os autores apresentam um caso de bronquiectasias conseqüentes à permanência de um corpo extranho vegetal na desembocadura dos brônquios inferior e médio do pulmão direito, há 7 anos. Fazem considerações sôbre a fisiopatologia do processo e chamam a atenção para as gravidades da reação ao corpo extranho de origem vegetal. É importante o período assintomático que se segue à fase inicial. O diagnóstico deve basear-se na história, no exame físico, no estudo radiológico e no endoscópico. O prognóstico é grave se o corpo extranho não for removido.Para a cura completa das bronquiectasias e dos abcessos pulmonares a indicação de escolha é ressecção pulmonar.
Novel Approach to Venous Stenting: Tigertriever Temporary Stenting for the Evaluation of Pulsatile Tinnitus
Authors: Al‐Kawaz Mais N. , Epstein Kayla , Mocco J.
Published: April 2024

Objective

Pulsatile tinnitus can be significantly functionally debilitating, with venous sinus stenosis being a largely underrecognized etiology. Establishing a direct cause‐effect relationship can be particularly challenging in pulsatile tinnitus cases without idiopathic intracranial hypertension, and with multifocal, bilateral venous sinus stenoses.

Case Presentation

Herein, we present a patient with pulsatile tinnitus and bilateral transverse‐sigmoid sinus stenoses on diagnostic angiogram. Temporary stenting using a Tigertreiver was utilized to localize the symptomatic segment. Patient reported resolution of pulsatile tinnitus after deploying the temporary stentriever within the left sigmoid sinus. Subsequently, permanent stenting of the left sigmoid sinus was preformed resulting in complete resolution of symptoms.

Conclusion

We highlight the diagnostic challenges of patients presenting with pulsatile tinnitus and venous sinus stenoses, without idiopathic intracranial hypertension. While more experience is needed, temporary stenting may provide an improved method for assessing venous stenting efficacy in patients with pulsatile tinnitus.
The Ethics of Life as It Could Be: Do We Have Moral Obligations to Artificial Life?
Authors: Witkowski Olaf , Schwitzgebel Eric
Published: April 2024

The field of Artificial Life studies the nature of the living state by modeling and synthesizing living systems. Such systems, under certain conditions, may come to deserve moral consideration similar to that given to nonhuman vertebrates or even human beings. The fact that these systems are nonhuman and evolve in a potentially radically different substrate should not be seen as an insurmountable obstacle to their potentially having rights, if they are sufficiently sophisticated in other respects. Nor should the fact that they owe their existence to us be seen as reducing their status as targets of moral concern. On the contrary, creators of Artificial Life may have special obligations to their creations, resembling those of an owner to their pet or a parent to their child. For a field that aims to create artificial life-forms with increasing levels of sophistication, it is crucial to consider the possible ethical implications of our activities, with an eye toward assessing potential moral obligations for which we should be prepared. If Artificial Life is larger than life, then the ethics of artificial beings should be larger than human ethics.
Synaptic Information Storage Capacity Measured With Information Theory
Authors: Samavat Mohammad , Bartol Thomas M. , Harris Kristen M. , Sejnowski Terrence J.
Published: April 2024

Variation in the strength of synapses can be quantified by measuring the anatomical properties of synapses. Quantifying precision of synaptic plasticity is fundamental to understanding information storage and retrieval in neural circuits. Synapses from the same axon onto the same dendrite have a common history of coactivation, making them ideal candidates for determining the precision of synaptic plasticity based on the similarity of their physical dimensions. Here, the precision and amount of information stored in synapse dimensions were quantified with Shannon information theory, expanding prior analysis that used signal detection theory (Bartol et al., 2015). The two methods were compared using dendritic spine head volumes in the middle of the stratum radiatum of hippocampal area CA1 as well-defined measures of synaptic strength. Information theory delineated the number of distinguishable synaptic strengths based on nonoverlapping bins of dendritic spine head volumes. Shannon entropy was applied to measure synaptic information storage capacity (SISC) and resulted in a lower bound of 4.1 bits and upper bound of 4.59 bits of information based on 24 distinguishable sizes. We further compared the distribution of distinguishable sizes and a uniform distribution using Kullback-Leibler divergence and discovered that there was a nearly uniform distribution of spine head volumes across the sizes, suggesting optimal use of the distinguishable values. Thus, SISC provides a new analytical measure that can be generalized to probe synaptic strengths and capacity for plasticity in different brain regions of different species and among animals raised in different conditions or during learning. How brain diseases and disorders affect the precision of synaptic plasticity can also be probed.
Saudi Arabia — The New Civil Transactions Law
Authors: Bälz Kilian , Fawzy Farah
Published: April 2024

On 16 December 2023, the new Saudi Civil Transactions Law entered into force. The law, for the first time, provides a comprehensive codification of contract, tort, and property law in Saudi Arabia, hereby replacing Sharīʿah principles that the courts relied on in the past. The law is a milestone in the modernization of Saudi economic law. First, the codification will enhance legal certainty, given that it was often difficult to predict how a Saudi court would apply Sharīʿah principles to a present-day commercial contract. Second, the legal enactment demonstrates that the Saudi legislature does not shy away from legislating core areas of law and replacing Sharīʿah rules that — in theory — continue to be the supreme law of the land. In substance, many provisions of the new law appear to be inspired by Egyptian law. The implementation in Saudi judicial practice remains to be seen.
Personal Status in Lebanon Versus Optional Civil Marriage
Authors: Hachem Talal , Karam Bechara
Published: April 2024

Marriage in Lebanon is a matter of religious law, and all attempts at introducing a civil marriage law have failed so far. This Article discusses the absence of a civil marriage law: was the Lebanese system supposed to include a civil marriage law? Is there a real need for it? Why have all legislative interventions failed? What are the alternatives? To answer these questions, we will focus mainly on the 1998 project of a civil Personal status law presented by President Hrawi, being the most complete and advanced attempt so far. The reactions for or against it are most representative of the Lebanese situation. We reach the conclusion that past legislative attempts always failed ‘upstream’, never reaching the Parliament, while contractual alternatives are not a viable option. The introduction of a civil marriage law, despite its necessity, cannot be achieved by mere legal means, but needs a governance-level answer.
Tactile Landmarks: the Relative Landmark Location Alters Spatial Distortions
Authors: Soballa Paula , Frings Christian , Merz Simon
Published: April 2024

The influence of landmarks, that is, nearby non-target stimuli, on spatial perception has been shown in multiple ways. These include altered target localization variability near landmarks and systematic spatial distortions of target localizations. Previous studies have mostly been conducted in the visual modality using temporary, artificial landmarks or the tactile modality with persistent landmarks on the body. Thus, it is unclear whether both landmark types produce the same spatial distortions as they were never investigated in the same modality. Addressing this, we used a novel tactile setup to present temporary, artificial landmarks on the forearm and systematically manipulated their location to either be close to a persistent landmark (wrist or elbow) or in between both persistent landmarks at the middle of the forearm. Initial data (Exp. 1 and Exp. 2) suggested systematic differences of temporary landmarks based on their distance from the persistent landmark, possibly indicating different distortions of temporary and persistent landmarks. Subsequent control studies (Exp. 3 and Exp. 4) showed this effect was driven by the relative landmark location within the target distribution. Specifically, landmarks in the middle of the target distribution led to systematic distortions of target localizations toward the landmark, whereas landmarks at the side led to distortions away from the landmark for nearby targets, and toward the landmark with wider distances. Our results indicate that experimental results with temporary landmarks can be generalized to more natural settings with persistent landmarks, and further reveal that the relative landmark location leads to different effects of the pattern of spatial distortions.
Using wood rings to determine age and climate constraints of grapevine (Vitis vinifera) radial growth
Authors: Camarero J. Julio , Colangelo Michele , Pecora Giovanni , Valeriano Cristina
Published: April 2024

Grapevine (Vitis vinifera) is the most widely cultivated and economically relevant crop in the world, but its productivity is menaced by aridification in some wine-growing regions such as the Mediterranean Basin. The impacts of climate on vines depend on regional conditions, cultivar, and vine age, among other factors. Hence, a better understanding of vine radial-growth responses to climate in different regions is sorely needed. First, we related climate data and drought severity with a long-term series of vine leaf unfolding from NE Spain to test if climate warming is advancing the onset of the growing season. Second, we used growth rings to estimate age and quantify climate-growth relationships of vines using dendrochronology. Three sites from different designations of origin and vine varieties were studied: Logroño in northern Spain (La Rioja, Tempranillo), San Martín del Río in northeast Spain (Calatayud, Garnacha) and Anzi in southern Italy (Aglianico, Aleatico). Vine leaf unfolding occurred earlier as winter-spring conditions were warmer and drier. Vine ages ranged between 16 (Logroño, Anzi) and 56 years (S. Martín del Río), and growth rates declined in the two youngest grapevines. Ring widths varied between 1.19 (S. Martín del Río) and 1.80 mm (Logroño), with Anzi showing intermediate values (1.37 mm). February precipitation enhanced vine growth in San Martín del Río () and Anzi (), whereas the correlation with soil moisture peaked in March in San Martín del Río (). Vine growth rates positively responded to September minimum temperatures in San Martín del Río () and Logroño (). Garnacha cultivar in San Martín del Río showed the highest responsiveness to water availability. Therefore, similar old grapevines from continental, seasonally dry areas could be the most negatively affected by future warmer and drier climate conditions.
The Value of CT Examination in the Development of Imaging Manifestations of Acute High Altitude Pulmonary Edema
Authors: Wang Bo , Shen Caifu , Wang Ying , Jia Qingjian , Liu Rongtao , Liu Xinwen , Hu Wenjiang , Wang Yubin , Yang Xuemei
Published: April 2024

This study aims to analyze the significance of CT examinations in elucidating the imaging manifestations of acute high-altitude pulmonary edema (HAPE). A cohort of 200 patients with acute HAPE, attending the clinic between January 2021 and January 2022, constituted the subjects. Employing
distinct examination methods, participants were categorized into a control group (undergoing X-ray examinations, n = 100) and an observation group (undergoing CT examinations, n = 100). Comprehensive patient data were collected, facilitating a comparative analysis of examination
results, diagnosis rates, imaging features, and related indicators between the two groups. No statistically significant differences were evident, signifying comparable profiles (P >0.05). However, the observation group exhibited significantly superior examination outcomes compared
to the control group (P < 0.01). The diagnostic rate in the observation group reached 98.00%, surpassing the control group’s nursing efficiency at 92.00%. This observed superiority of the observation group was statistically significant (P < 0.01). While both X-ray
and CT methods detected high-altitude pulmonary edema, CT examinations provided clearer insights into specific lesions, enhancing accuracy and diagnosis rates. This study underscores the paramount significance of high-altitude pulmonary edema examinations, particularly advocating for the widespread
adoption of CT technology.
Development of an Efficient Therapeutic Strategy in Oral Squamous Cell Carcinoma: A Novel Nanoplatform for siATG5 Delivery
Authors: Chang-Zhu  , Pang Yong-Zhi , Zhang Feng-He
Published: April 2024

As is well known, autophagy activation is associated with the progression of oral squamous cell carcinoma (OSCC) cells, and regulating the development of autophagy is beneficial for improving cancer treatment. ATG5 plays an irreplaceable role in autophagy and many important processes
of cell, can be used as a therapeutic target for tumors. We use G0-C14 cationophore, which efficiently carries siATG5 to form stable nanoparticles (siA/NPs). SiA/NPs successfully escapes lysosomes, releases siATG5 and efficiently silences ATG5, has a certain OSCC lethality. This provides a
direction for the targeted autophagy treatment of future OSCC therapy.
Non-Binary Trauma Patients: Delineating a Vulnerable, At-Risk Population
Authors: Hambrecht Amanda , Schellenberg Morgan , Owattanapanich Natthida , Boyle Kelly A. , Ugarte Chaiss , Ambrose Corey , Matsushima Kazuhide , Martin Matthew J. , Inaba Kenji
Published: April 2024

Introduction

An increasing proportion of the population identifies as non-binary. This marginalized group may be at differential risk for trauma compared to those who identify as male or female, but physical trauma among non-binary patients has not yet been examined at a national level.

Methods

All patients aged ≥ 16 years in the National Trauma Data Bank were included (2021-2022). Demographics, injury characteristics, and outcomes after trauma among non-binary patients were compared to males and females. The goal was to delineate differences between groups to inform the care and future study of non-binary trauma patients.

Results

In total, 1,012,348 patients were included: 283 (<1%) non-binary, 610,904 (60%) male, and 403,161 (40%) female patients. Non-binary patients were younger than males or females (median age 44 vs 49 vs 67 years, P < .001) and less likely to be White race/ethnicity (58% vs 60% vs 74%, P < .001). Despite non-binary patients having a lower median Injury Severity Score (5 vs 9 vs 9, P < .001), mortality was highest among non-binary and male patients than females (5% vs 5% vs 3%, P < .001).

Discussion

In this study, non-binary trauma patients were younger and more likely minority races/ethnicities than males or females. Despite having a lower injury severity, non-binary patient mortality rates were comparable to those of males and greater than for females. These disparities identify non-binary trauma patients as doubly marginalized, by gender and race/ethnicity, who experience worse outcomes after trauma than expected based on injury severity. This vulnerable patient population deserves further study to identify areas for improved trauma delivery care.
The Impact of Postoperative COVID-19 Infection on 30-day Outcomes of Laparoscopic Cholecystectomy
Authors: Moulton Alexandra , Liu Jessica K. , Miguel de Virgilio Christian , Ozao-Choy Junko , Moazzez Ashkan
Published: April 2024

Introduction: Preoperative Coronavirus Disease 2019 (COVID-19) infections are associated with postoperative adverse outcomes. However, there is limited data on the impact of postoperative COVID-19 infection on postoperative outcomes of common general surgery procedures.

Objective: To evaluate the impact of postoperative COVID-19 diagnosis on laparoscopic cholecystectomy outcomes.

Methods: Patients with symptomatic cholelithiasis, acute cholecystitis, or gallstone pancreatitis who underwent laparoscopic cholecystectomy with or without intraoperative cholangiogram were identified using the 2021 National Surgical Quality Improvement Program (NSQIP) database. Patients were categorized into two groups: patients with and without a postoperative COVID-19 diagnosis. Coarsened Exact Matching was used to match the groups based on preoperative risk factors, and outcomes were compared.

Results: A total of 47,948 patients were included. In the aggregate cohort, 31% were male, and mean age was 50 years. Age, BMI, smoking, COPD, CHF, preoperative sepsis, and ASA class were significantly different between the two groups. After matching, there were no differences in characteristics. 30-day morbidity (OR = 2.7, 95% CI 1.4-5.1), pneumonia (OR = 5.0, 95% CI 1.7-15.0), DVT (OR = 8.22, 95% CI 1.0-66), reoperation (OR = 9.3, 95% CI 1.2-73.8), and readmission (OR = 4.8, 95% CI 2.3-10.1) continued to be significantly worse in the matched cohort.

Conclusion: Postoperative COVID-19 infection was associated with worse outcomes after laparoscopic cholecystectomy. These findings suggest that even postoperative COVID-19 diagnosis increases the risk for adverse outcomes in patients recovering from laparoscopic cholecystectomy and may indicate that precautions should be taken and new COVID-19 infections even after surgery should be closely monitored.
Closing the Innovation Performance Gap: Open Innovation in Military Bureaucracies
Authors: Heeren Jasper , van de Vrande Vareska , Volberda Henk , de Waard Erik
Published: April 2024

This article explores the effects of open innovation on innovation performance in military bureaucracies. While the understanding of how bureaucratic organizations can benefit from open innovation is still limited, this study discovered that open innovation can have a negative effect on innovation performance. However, leveraging an innovative culture can lead to improved innovation performance in organizations characterized by high levels of structure and hierarchy, especially those where secrecy and security are of vital importance.
Americanized discourses of religious freedom and Christian persecution during the 2022 Ottawa trucker convoy
Authors: Dick Hannah
Published: April 2024

In this article, Hannah Dick draws on Stewart Hoover’s concept of mediated imaginaries to help explain the transnational circulation of Americanized discourses during the 2022 Canadian trucker convoy protest in Ottawa. She examines the mediated objects produced by the convoy participants, including physical signs erected throughout downtown Ottawa and also those that circulated on social media platforms and in official communications published by convoy leaders. Using textual analysis, she explores the role of Americanized Christian discourses in charging the Canadian convoy movement with both political and existential meaning. It is argued that while the convoy does not represent a simple importation of American religio-political organizing consistent with theories of cultural imperialism, the symbolic resonances of Americanized discourses of freedom and Christian persecution nevertheless provide a flexible and robust affective infrastructure that is adaptable for the Canadian context.
A content analysis of freely available menstrual education resources in Australia
Authors: Blackmore Bianca , Moran Claire , Wigginton Britta
Published: April 2024

Background:

Sexual and reproductive health education is central to both international and national public health policy and priority action areas. However, menstruation education remains peripheral in both policy and school curricula. This article aims to investigate the extent and depth of menstruation education in Australia available outside of mainstream education channels.

Methods:

We conducted an inductive content analysis of publicly available Australian sexual and reproductive health educational resources targeting young menstruators and parents, which at least mentioned menstruation. Resources were accessed via a desktop search (using Google) to ensure that they were accessible to the public and were provided by not-for-profit or government organisations.

Results:

We identified a total of 31 resources from 10 organisations and subjected them to conventional content analysis. Our inductive coding process focused on the extent and depth of menstruation content. The main content areas included a discussion of pads and tampons, menarche, period pains, when to see a doctor and pre-menstrual syndrome. Three key themes were identified across the resources: holism, normalisation and managing menstruation.

Conclusions:

We develop recommendations for organisations developing or improving their menstruation resources and offer future direction for sexual and reproductive health policy and education in Australia that is inclusive of menstruation. The recommendations relate to the three themes identified during the analysis and include concepts such as recognising the biological changes that come with menstruation, variation of menstruation experiences, normality and assumptions about menstruation and menstrual hygiene management.
Study of the tensile mechanical properties and failure mechanisms of CFRP screwed joints
Authors: He Renyu , Yang Tao , Liu Sinan , Zhang Pengchao , Liu Chang , Yuan Wenhui , Du Yu
Published: April 2024

Removable joint technology is commonly used in composite laminates for various load-bearing structures. However, existing research primarily focuses on bolted joints, there is relatively limited research on screwed joints in composite materials. This study investigates the influence of connected layer thickness and hole diameter on the tensile behavior of threaded joints in carbon fiber-reinforced polymer (CFRP) laminates. After fabricating different CFRP screwed joint specimens, tensile tests were conducted. The digital image correlation (DIC) technique captured the deformation process. The experiment results indicate a significant increase in load-bearing capacity with the increase in diameter. For instance, joints with an 8 mm diameter exhibited a load-bearing capacity of 10.82 kN. The increase in the connected layer thickness correspondingly enhanced the load-bearing capacity of the joint. The joint with a thickness of 7 mm had the highest load-bearing capacity of 8.83 kN. Besides, with the increase in the thickness of the connected layer, the failure mode transitioned from shear failure in the connected layer to screw pull-out. The tilt angle of the screw during the pull-out process also decreases with the increase in the connected layer thickness. Strain and out-of-plane displacement measurements under ultimate load conditions verify these observations.
Awareness and Attitudes toward Health Education and Promotion among Physicians and Nurses: Implications for Primary Health Care
Authors: Alissa Nawal A. , Alwargash Mohammed
Published: April 2024

Health promotion and education are collaborative efforts involving patients, healthcare providers, and society, crucial for preventing and managing disease outbreaks. However, in Saudi Arabia, the actual or perceived endeavors of physicians and nurses in health education and promotion are not widely understood, which holds significant implications for those working in the field. This study aimed to evaluate the level of awareness and attitude toward health education and promotion among physicians and nurses in primary healthcare centers in Najran, Saudi Arabia. A descriptive cross-sectional study design was employed, and 187 participants were incorporated into the analysis. Questionnaires were distributed to physicians and nurses at the primary health care centers. Participants completed a face-to-face survey questionnaire about their awareness and attitude toward health education and promotion. One of the authors was physically present at the primary health care centers to assist the participants with answering the questionnaire questions. Saudis and physicians had higher awareness than non-Saudis and nurses, respectively. Work experience and institutional factors did not significantly influence awareness. A positive correlation between awareness and attitude was observed. However, perceived shortcomings in current approaches were identified, including a lack of skills and training, poor communication, and inadequate leadership support. Despite these challenges, healthcare professionals held positive attitudes toward health education, recognizing its importance in behavior change, reducing disparities, and influencing community policies. The study highlights the need for targeted interventions, including research on effective models, training programs, and improved communication and leadership support, to address identified gaps and optimize health education implementation.
Chondrosarcoma of the Nasal Cavity and Paranasal Sinuses: A Rare Entity
Authors: Malika El Omri , Ben Njima Marwa , Mouna Bellakhdher , Zeineb Nfikha , Wassim Kemani , Badreddine Sriha , Mohamed Abdelkefi
Published: April 2024

Background: Chondrosarcomas are slow-growing malignant tumors that originate in cartilaginous structures. They typically manifest in the head and neck region, with a preference for the maxillofacial skeleton, particularly the mandible and maxilla. However, chondrosarcoma of the sinonasal tract is exceptionally rare, and only few cases have been reported. Case Presentation: This report details the case of a 43-year-old woman who incidentally discovered chondrosarcoma in the maxillary and ethmoid sinuses with nasal extension. Subsequently, the patient underwent surgery via a paralatero-nasal approach with adjuvant radiotherapy. The aim of this study was to describe the clinical findings, management, and outcome of sinonasal tract chondrosarcoma. Conclusions: The primary treatment for chondrosarcomas remains surgery, with a transnasal endoscopic approach offering a viable option for complete resection in select cases.
Relationships on a Pedestal: The Associations Between Relationship Pedestal Beliefs, Fear of Being Single, and Life Satisfaction in Single and Coupled Individuals
Authors: Dennett Brittany E. , Girme Yuthika U.
Published: April 2024

The fear of being single can put people at risk for worse personal and relational well-being. The current research moves beyond individual-deficit models by exploring whether endorsement of relationship pedestal beliefs—the belief that people need to be in a relationship to be truly happy—is associated with greater fear of being single. Across four studies ( N = 641 single individuals and 256 coupled individuals), single individuals’ endorsement of relationship pedestal beliefs was associated with greater fear of being single, and greater fear of being single was associated with lower daily life satisfaction (Studies 1–4). Coupled individuals’ endorsement of relationship pedestal beliefs was also associated with greater fear of being single, and greater fear of being single was associated with lower daily life and relationship satisfaction (Study 4). These findings highlight how people’s endorsement of societal beliefs that place relationships on a pedestal may contribute to fears about singlehood.