bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects of Different Levels of Potassium Diformate and Calcium Diformate on Growth, Digestion Enzyme Activity, Antioxidant Capacity, Intestinal Flora, Stress Markers, and Some Serum Biochemical Analytes in Juvenile Beluga Huso huso
Authors: Sayah Abdollah Beit , Mohammadian Takavar , Mesbah Mehrzad , Jalali Seyedeh Misagh , Tabandeh Mohammad Reza
Published: April 2024

Potassium diformate (KDF) and calcium diformate (CaDF) are organic acids that modulate growth performance, stress, and biochemical status. So, the present study aimed to investigate the effects of different levels of potassium diformate and calcium diformate on growth performance, stress markers, oxidant/antioxidant status, microbial flora, and some serum biochemical analytes in juvenile Beluga (mean weight: 34 ± 4.5 g). Juvenile Beluga fed control food or diet supplemented with different levels of KDF (1, 1.5, and 2 g/kg) and CaDF (1, 1.5, and 2 g/kg) for 60 days. The results showed that fish fed the 0.15% (1.5 g/kg) KDF showed the favorable growth value at 30 days and relatively less, 0.15% CaDF improved significantly (P < 0.05) fish growth performance following 60 days of application (P < 0.05). The results showed that dietary administration of KDF and CaDF significantly (P < 0.05) increased digestive enzymes. Moreover, elevated biochemical parameters were observed in H. huso fed KDF and CaDF supplemented the diet. Serum oxidant/antioxidant status was significantly (P < 0.05) improved in the KDF and CaDF treatments than the control group. Moreover, dietary administration of KDF and CaDF significantly (P < 0.05) decreased stress markers of H. huso after 60 days. The liver enzymes activities considerably altered in the KDF and CaDF groups compared with the control group after 60 days. Furthermore, dietary administration of KDF and CaDF significantly (P < 0.05) increased intestinal lactic acid bacteria (LAB) of H. huso after 60 days. Based on the results of this study, it appears that incorporating KDF and CaDF into the diet of H. huso can have positive effects on their growth performance and physiological response. The study found that a short‐term use of 0.15% (1.5) g/kg of KDF for 30 days was the most effective in promoting growth. However, the potential use of 0.2% (2 g/kg) of KDF and 0.15% (1.5 g/kg) of CaDF for a longer period of 60 days may also be beneficial.
Diversity and Distribution of Avifauna in the Northeast of Addis Ababa, Central Ethiopia
Authors: Desalegn Tamenut , Abebe Belayneh
Published: April 2024

Exploring avian species diversity and distribution patterns is vigorous for conservation efforts in biodiversity-rich countries such as Ethiopia. Compared to other species, birds are relatively well-known and easily observed, making them great markers of productivity or biodiversity. Although bird species are found all across the world, their survival and range have been negatively impacted by habitat loss, fragmentation, and destruction. Thus, the goal of this study is to provide baseline data on avifaunal diversity in the Northeast of Addis Ababa, including species richness, distribution, and relative abundance in various habitats conducted from January 2023 to September 2023 using a stratified sampling design into three habitat types: settlement, farmland, and abattoir. A fixed-width line transect sampling method was used at the farmland and settlement, and a point transect was employed at the abattoir site to collect the bird data. The data were compared using Mann–Whitney and Kruskal–Wallis statistical tests in both seasons and habitat types. A total of 42 bird species belonging to twenty-three families, and nine orders were recorded during the study period. Of these, blue-winged goose and wattled ibis are endemic to Ethiopia. Hooded vultures and White-backed vultures are critically endangered species. The mean abundance of bird species significantly varied in the three habitat types (χ2 = 13.6, df = 2, p=0.001). The abundance of bird species was nonsignificant difference between wet and dry seasons (U = −0.874, p=0.381). The highest diversity (H′ = 2.74) was recorded at settlement, and the lowest diversity index (H′ = 1.09) was recorded at the abattoir in the dry season. In the wet season, the highest diversity (H′ = 2.66) was recorded in the farmland, and the lowest (H′ = 1.08) was recorded at the abattoir. The highest evenness (J = 0.94 and J = 0.93) was recorded on the farmland in the wet and dry seasons, respectively. In the study area, urbanization is extremely impacting the environment and altering ecosystem services upon which human civilization depends. Most of the avian species observed in the study area are capable and tolerant of human-induced habitats in the city. Therefore, city planners must consider conserving urban bird species’ habitats and feeding sites.
Utilizing Local Waste: Sustainable Adsorption of Reactive Blue 235 on Surfactant‐Modified Bamboo Fibers
Authors: Vaid Samriti , Kaur Varinder , Sharma Sanyog , Singh Anupinder , Vaid Bhavna , Arya Raj Kumar , Verros G. D.
Published: April 2024

In this research endeavor, we sought to enhance the efficacy of bamboo fibers through modification with the surfactant cetyltrimethylammonium bromide (CTAB) for the purpose of removing Reactive Blue 235 from effluent. Our investigation encompassed a comprehensive exploration of the impact of crucial parameters, namely, adsorbent dosage (0.25 g–1.25 g), contact time (10–80 min), pH (2–12), initial dye concentration (20–100 mg/L), and temperature (298 K, 308 K, and 318 K) on the dynamics of dye removal. The optimum dye removal efficiency of 94% for Reactive Blue 235 was obtained at an adsorbent dosage of 0.5 g/50 ml of dye solution, initial dye concentration of 40 mg/L, pH of 6, and contact time of 40 min. The experimental framework included the anticipation of data aligned with various isothermal and kinetic models, facilitating a nuanced understanding of the adsorption process. Our findings unveiled that the kinetics of adsorption adhered to a second‐order model, while the Langmuir isotherm model aptly described the adsorption behavior. Particularly noteworthy was the monolayer’s adsorption capacity, quantified at an impressive 7.39 mg·g−1 at a temperature of 318 K. The value of Freundlich’s constant, KF, increases with an increase in temperature indicating the endothermic nature of adsorption. The magnitude of E obtained from Dubinin–Radushkevich isotherm varying from 3.92 to 4.66 kJ/mol on increasing temperature from 298 K to 318 K suggests that adsorption of RB235 on BAT is a physisorption (value of E is between 1 and 8 kJ/mol). Delving into the thermodynamic aspects of the process, we calculated ΔH and ΔS to be 54.88 kJ/mol and 184.54 J/mol/K, respectively. The consistently negative values of ΔG (between −0.183 kJ/mol and −3.884 kJ/mol) at all temperatures underscored the feasibility, spontaneity, and entropy‐driven nature of the adsorption of RB235 on CTAB‐treated bamboo fiber (BAT). What sets our study apart is the deliberate utilization of bamboo fibers sourced from local waste streams, embodying a commitment to sustainable practices. Beyond its effectiveness in effluent treatment, our approach aligns with eco‐friendly principles by repurposing indigenous waste materials, contributing to a more sustainable and environmentally responsible future.
GPR1 and CMKLR1 Control Lipid Metabolism to Support the Development of Clear Cell Renal Cell Carcinoma
Authors: Wang Dazhi , Mahmud Iqbal , Thakur Vijay S. , Tan Sze Kiat , Isom Daniel G. , Lombard David B. , Gonzalgo Mark L. , Kryvenko Oleksandr N. , Lorenzi Philip L. , Tcheuyap Vanina T. , Brugarolas James , Welford Scott M.
Published: April 2024

Clear cell renal cell carcinoma (ccRCC), the most common type of kidney cancer, is largely incurable in the metastatic setting. ccRCC is characterized by excessive lipid accumulation that protects cells from stress and promotes tumor growth, suggesting that the underlying regulators of lipid storage could represent potential therapeutic targets. Here, we evaluated the regulatory roles of GPR1 and CMKLR1, two G protein–coupled receptors of the protumorigenic adipokine chemerin that is involved in ccRCC lipid metabolism. Both genetic and pharmacologic suppression of either receptor suppressed lipid formation and induced multiple forms of cell death, including apoptosis, ferroptosis, and autophagy, thereby significantly impeding ccRCC growth in cell lines and patient-derived xenograft models. Comprehensive lipidomic and transcriptomic profiling of receptor competent and depleted cells revealed overlapping and unique signaling of the receptors granting control over triglyceride synthesis, ceramide production, and fatty acid saturation and class production. Mechanistically, both receptors enforced suppression of adipose triglyceride lipase, but each receptor also demonstrated distinct functions, such as the unique ability of CMKLR1 to control lipid uptake through regulation of sterol regulatory element–binding protein 1c and the CD36 scavenger receptor. Treating patient-derived xenograft models with the CMKLR1-targeting small molecule 2-(α-naphthoyl) ethyltrimethylammonium iodide (α-NETA) led to a dramatic reduction in tumor growth, lipid storage, and clear-cell morphology. Together, these findings provide mechanistic insights into lipid regulation in ccRCC and identify a targetable axis at the core of the histologic definition of this tumor that could be exploited therapeutically.

Significance: Extracellular control of lipid accumulation via G protein receptor–mediated cell signaling is a metabolic vulnerability in clear cell renal cell carcinoma, which depends on lipid storage to avoid oxidative toxicity.
Association of Ideal Cardiovascular Health in Youth with Cancer Risk in Adulthood: A Cardiovascular Risk in Young Finns Study
Authors: Niemelä Jussi , Nuotio Joel , Laitinen Tomi T. , Kähönen Mika , Hutri Nina , Lehtimäki Terho , Jokinen Eero , Tossavainen Päivi , Laitinen Tomi P. , Heinonen Olli J. , Dwyer Terence , Pahkala Katja , Rovio Suvi P. , Viikari Jorma , Raitakari Olli , Juonala Markus
Published: April 2024

Background:

Lifestyle factors may affect cancer risk. This study aimed to identify whether the American Heart Association ideal cardiovascular health (ICH) score and its individual variables in youth are associated with subsequent cancer incidence.

Methods:

This study comprised participants of the Cardiovascular Risk in Young Finns Study free of cancer at the analysis baseline in 1986 (n = 1,873). The baseline age was 12 to 24 years, and the follow-up occurred between 1986 and 2018.

Results:

Among 1,873 participants (mean age 17.3 ± 4.1 years; 53.4% females at baseline), 72 incident cancer cases occurred during the follow-up (mean follow-up time 31.4 ± 3.4 years). Baseline ICH score was not associated with future cancer risk (HR, 0.96; 95% confidence interval, 0.78–1.12 per 1-point increment). Of individual ICH score variables, ideal physical activity (PA) was inversely associated with cancer incidence [age- and sex-adjusted HR, 0.45 (0.23–0.88) per 1-category change (nonideal/ideal)] and remained significant in the multivariable-adjusted model, including body mass index, smoking, diet, and socioeconomic status. A continuous PA index at ages 9 to 24 years and moderate-to-vigorous PA in youth were also related to decreased cancer incidence (P < 0.05). Body mass index, smoking, diet, total cholesterol, glucose, and blood pressure were not related to cancer risk. Of the dietary components, meat consumption was associated with cancer incidence (P = 0.023).

Conclusions:

These findings indicate that higher PA levels in youth are associated with a reduced subsequent cancer incidence, whereas the American Heart Association’s ICH score in youth does not.

Impact:

This finding supports efforts to promote a healthy lifestyle and encourages PA during childhood, yielding a subsequent healthier life.
Supplementary Data from MAPK Pathway Genetic Alterations Are Associated with Prolonged Overall Survival in Low-Grade Serous Ovarian Carcinoma
Authors: Manning-Geist Beryl , Gordhandas Sushmita , Liu Ying L. , Zhou Qin , Iasonos Alexia , Da Cruz Paula Arnaud , Mandelker Diana , Long Roche Kara , Zivanovic Oliver , Maio Anna , Kemel Yelena , Chi Dennis S. , O'Cearbhaill Roisin E. , Aghajanian Carol , Weigelt Britta , Chui M. Herman , Grisham Rachel N.
Published: April 2024

Supplementary Data from MAPK Pathway Genetic Alterations Are Associated with Prolonged Overall Survival in Low-Grade Serous Ovarian Carcinoma
A Cohort Study to Evaluate Genetic Predictors of Aromatase Inhibitor Musculoskeletal Symptoms: Results from ECOG-ACRIN E1Z11
Authors: Stearns Vered , Jegede Opeyemi A. , Chang Victor T.-S. , Skaar Todd C. , Berenberg Jeffrey L. , Nand Ranveer , Shafqat Atif , Jacobs Nisha L. , Luginbuhl William , Gilman Paul , Benson Al B. , Goodman Judie R. , Buchschacher Gary L. , Henry N. Lynn , Loprinzi Charles L. , Flynn Patrick J. , Mitchell Edith P. , Fisch Michael J. , Sparano Joseph A. , Wagner Lynne I.
Published: April 2024

Purpose:

Aromatase inhibitor (AI)–associated musculoskeletal symptoms (AIMSS) are common and frequently lead to AI discontinuation. SNPs in candidate genes have been associated with AIMSS and AI discontinuation. E1Z11 is a prospective cohort study designed to validate the association between 10 SNPs and AI discontinuation due to AIMSS.

Patients and Methods:

Postmenopausal women with stage I to III hormone receptor–positive breast cancer received anastrozole 1 mg daily and completed patient-reported outcome measures to assess AIMSS (Stanford Health Assessment Questionnaire) at baseline, 3, 6, 9, and 12 months. We estimated that 40% of participants would develop AIMSS and 25% would discontinue AI treatment within 12 months. Enrollment of 1,000 women with a fixed number per racial stratum provided 80% power to detect an effect size of 1.5 to 4. SNPs were found in ESR1 (rs2234693, rs2347868, and rs9340835), CYP19A1 (rs1062033 and rs4646), TCL1A (rs11849538, rs2369049, rs7158782, and rs7159713), and HTR2A (rs2296972).

Results:

Of the 970 evaluable women, 43% developed AIMSS and 12% discontinued AI therapy within 12 months. Although more Black and Asian women developed AIMSS than White women (49% vs. 39%, P = 0.017; 50% vs. 39%, P = 0.004, respectively), the AI discontinuation rates were similar across groups. None of the SNPs were significantly associated with AIMSS or AI discontinuation in the overall population or in distinct cohorts. The OR for rs2296972 (HTR2A) approached significance for developing AIMSS.

Conclusions:

We were unable to prospectively validate candidate SNPs previously associated with AI discontinuation due to AIMSS. Future analyses will explore additional genetic markers, patient-reported outcome predictors of AIMSS, and differences by race.
Integrating Multisector Molecular Characterization into Personalized Peptide Vaccine Design for Patients with Newly Diagnosed Glioblastoma
Authors: Johanns Tanner M. , Garfinkle Elizabeth A.R. , Miller Katherine E. , Livingstone Alexandra J. , Roberts Kaleigh F. , Rao Venkata Lakshmi P. , Dowling Joshua L. , Chicoine Michael R. , Dacey Ralph G. , Zipfel Gregory J. , Kim Albert H. , Mardis Elaine R. , Dunn Gavin P.
Published: April 2024

Purpose:

Outcomes for patients with glioblastoma (GBM) remain poor despite multimodality treatment with surgery, radiation, and chemotherapy. There are few immunotherapy options due to the lack of tumor immunogenicity. Several clinical trials have reported promising results with cancer vaccines. To date, studies have used data from a single tumor site to identify targetable antigens, but this approach limits the antigen pool and is antithetical to the heterogeneity of GBM. We have implemented multisector sequencing to increase the pool of neoantigens across the GBM genomic landscape that can be incorporated into personalized peptide vaccines called NeoVax.

Patients and Methods:

In this study, we report the findings of four patients enrolled onto the NeoVax clinical trial (NCT0342209).

Results:

Immune reactivity to NeoVax neoantigens was assessed in peripheral blood mononuclear cells pre- and post-NeoVax for patients 1 to 3 using IFNγ-ELISPOT assay. A statistically significant increase in IFNγ producing T cells at the post-NeoVax time point for several neoantigens was observed. Furthermore, a post-NeoVax tumor biopsy was obtained from patient 3 and, upon evaluation, revealed evidence of infiltrating, clonally expanded T cells.

Conclusions:

Collectively, our findings suggest that NeoVax stimulated the expansion of neoantigen-specific effector T cells and provide encouraging results to aid in the development of future neoantigen vaccine–based clinical trials in patients with GBM. Herein, we demonstrate the feasibility of incorporating multisector sampling in cancer vaccine design and provide information on the clinical applicability of clonality, distribution, and immunogenicity of the neoantigen landscape in patients with GBM.
A Machine Learning Algorithm Facilitates Prognosis Prediction and Treatment Selection for Barcelona Clinic Liver Cancer Stage C Hepatocellular Carcinoma
Authors: Han Ji W. , Lee Soon K. , Kwon Jung H. , Nam Soon W. , Yang Hyun , Bae Si H. , Kim Ji H. , Nam Heechul , Kim Chang W. , Lee Hae L. , Kim Hee Y. , Lee Sung W. , Lee Ahlim , Chang U I. , Song Do S. , Kim Seok-Hwan , Song Myeong J. , Sung Pil S. , Choi Jong Y. , Yoon Seung K. , Jang Jeong W.
Published: April 2024

Purpose:

Given its heterogeneity and diverse clinical outcomes, precise subclassification of Barcelona Clinic Liver Cancer stage C (BCLC-C) hepatocellular carcinoma (HCC) is required for appropriately determining patient prognosis and selecting treatment.

Experimental Design:

We recruited 2,626 patients with BCLC-C HCC from multiple centers, comprising training/test (n = 1,693) and validation cohorts (n = 933). The XGBoost model was chosen for maximum performance among the machine learning (ML) models. Patients were categorized into low-, intermediate-, high-, and very high-risk subgroups based on the estimated prognosis, and this subclassification was named the CLAssification via Machine learning of BCLC-C (CLAM-C).

Results:

The areas under the receiver operating characteristic curve of the CLAM-C for predicting the 6-, 12-, and 24-month survival of patients with BCLC-C were 0.800, 0.831, and 0.715, respectively—significantly higher than those of the conventional models, which were consistent in the validation cohort. The four subgroups had significantly different median overall survivals, and this difference was maintained among various patient subgroups and treatment modalities. Immune-checkpoint inhibitors and transarterial therapies were associated with significantly better survival than tyrosine kinase inhibitors (TKI) in the low- and intermediate-risk subgroups. In cases with first-line systemic therapy, the CLAM-C identified atezolizumab–bevacizumab as the best therapy, particularly in the high-risk group. In cases with later-line systemic therapy, nivolumab had better survival than TKIs in the low-to-intermediate-risk subgroup, whereas TKIs had better survival in the high- to very high-risk subgroup.

Conclusions:

ML modeling effectively subclassified patients with BCLC-C HCC, potentially aiding treatment allocation. Our study underscores the potential utilization of ML modeling in terms of prognostication and treatment allocation in patients with BCLC-C HCC.
NSCLC Extracellular Vesicles Containing miR-374a-5p Promote Leptomeningeal Metastasis by Influencing Blood‒Brain Barrier Permeability
Authors: Jin Jie , Cui Yumeng , Niu Huicong , Lin Yanli , Wu Xiaojie , Qi Xuejiao , Bai Kaixuan , Zhang Yu , Wang Youliang , Bu Hui
Published: April 2024

Leptomeningeal metastasis (LM) is a devastating complication of advanced non–small cell lung cancer (NSCLC). Its diagnosis and monitoring can be challenging. Recently, extracellular vesicle (EV) miRNAs have become a new noninvasive diagnostic biomarker. The purpose of this study was to examine the clinical value and role of EV miRNAs in NSCLC-LM. Next-generation sequencing analysis revealed that miRNAs with differential expression of EVs in sera of patients with NSCLC with LM and non-LM were detected to identify biological markers for the diagnosis of LM. Cellular and in vivo experiments were conducted to explore the pathogenesis of EV miRNA promoting LM in NSCLC. In the present study, we first demonstrated that the serum level of EV-associated miR-374a-5p in patients with LM of lung cancer was much higher than that in patients without LM and was correlated with the survival time of patients with LM. Further studies showed that EV miR-374a-5p efficiently destroys tight junctions and the integrity of the cerebral microvascular endothelial cell barrier, resulting in increased blood–brain barrier permeability. Mechanistically, miR-374a-5p regulates the distribution of ZO1 and occludin in endothelial cells by targeting γ-adducin, increasing vascular permeability and promoting LM.

Implications: These results suggest that serum NSCLC–derived EV miR-374a-5p is involved in premetastatic niche formation by regulating the permeability of the blood–brain barrier to promote NSCLC-LM and can be used as a blood biomarker for the diagnosis and prognosis of NSCLC-LM.
mTOR Signaling Promotes Rapid m6A mRNA Methylation to Regulate NK-Cell Activation and Effector Functions
Authors: Meng Meng , Zhong Zhaoyang , Song Liang , Zhang Zhaohui , Yin Xiaofeng , Xie Xiqiang , Tian Lei , Wu Wei , Yang Yao , Deng Yafei , Peng Hongyan , Wu Shuting , Ran Guanghe , Lin Yuqing , Lai Qiangqiang , Bi Qinghua , Yan Fulin , Ji Yan , Wang Yang , Li Xiaohui , Yi Ping , Yu Jianhua , Deng Youcai
Published: April 2024

NK cells can be rapidly activated in response to cytokines during host defense against malignant cells or viral infection. However, it remains unclear what mechanisms precisely and rapidly regulate the expression of a large number of genes involved in activating NK cells. In this study, we discovered that NK-cell N6-methyladenosine (m6A) methylation levels were rapidly upregulated upon short-term NK-cell activation and were repressed in the tumor microenvironment (TME). Deficiency of methyltransferase-like 3 (METTL3) or METTL14 moderately influenced NK-cell homeostasis, while double-knockout of METTL3/14 more significantly impacted NK-cell homeostasis, maturation, and antitumor immunity. This suggests a cooperative role of METTL3 and METTL14 in regulating NK-cell development and effector functions. Using methylated RNA immunoprecipitation sequencing, we demonstrated that genes involved in NK-cell effector functions, such as Prf1 and Gzmb, were directly modified by m6A methylation. Furthermore, inhibiting mTOR complex 1 activation prevented m6A methylation levels from increasing when NK cells were activated, and this could be restored by S-adenosylmethionine supplementation. Collectively, we have unraveled crucial roles for rapid m6A mRNA methylation downstream of the mTOR complex 1–S-adenosylmethionine signal axis in regulating NK-cell activation and effector functions.
Thoracic Duct Visualization in Esophageal Resection: A Pilot Trial
Authors: Berger Yael , Bard Vyacheslav , Abbas Muhammad , Solomon Daniel , Menasherov Nikolai , Kashtan Hanoch
Published: April 2024

Introduction: Inadvertent thoracic duct injury is common during esophagectomy and may result in postoperative chylothorax. This study’s objective was to investigate utility of patent blue injection as a modality for intraoperative thoracic duct visualization. Methods: A prospective, single-arm, interventional study of patients undergoing minimally invasive esophagectomy was performed. Patients were injected with patent blue dye into both groins prior to thoracic stage of surgery and assessed for duct visualization. Control group was formed by propensity score matching using retrospectively collected data regarding patients who underwent esophagectomy. Results: A total of 25 patients were included in analysis, compared to a control of 50 patients after matching. Thoracic duct was visualized in 60% of patients in the study group (15/25 patients). Significant differences were found between study and control groups (p < 0.05) with regards to median operative time (422 vs. 285 min, respectively), overall complications (16 vs. 34%, respectively), and median postoperative length of stay (13.5 vs. 10 days, respectively). There was a difference in rate of chyle leak between study and control groups; however, this was not significant (0 vs. 12%, respectively, p = 0.17). Conclusion: Patent blue injection represents a simple method for thoracic duct visualization during minimally invasive esophagectomy which may improve surgical outcomes.
Growth Hormone Therapy: Comparison of Short- and Long-Term Outcomes between Children with Growth Hormone Deficiency and Small for Gestational Age
Authors: Gleiss Andreas , Raimann Adalbert , Haufler Florentina , Ertl Diana-Alexandra , Sagmeister Susanne , Hartmann Gabriele
Published: April 2024

Introduction: Direct comparisons of both short-term and long-term auxological outcomes of growth hormone therapy (GHT) between growth hormone deficiency (GHD) and small for gestational age (SGA) are scarce. Methods: One hundred three patients with GHD and 53 patients with SGA treated at our tertiary center were investigated. Short-term and long-term outcomes were compared between these groups using multivariable linear regression models with adjustment for age, sex, and height at therapy start, also allowing for sex-specific group comparisons. Results: Mean delta height standard deviation scores (SDS) after 1 year of treatment were significantly higher in GHD (0.90, CI: 0.82–0.99) compared to SGA (0.67, CI: 0.54–0.79) (p = 0.003) with no sex difference. As expected, the mean increase in height SDS at final height (FH) was significantly higher in GHD (2.21, CI: 2.00–2.42) compared to SGA (1.05, CI: 0.75–1.35) (p < 0.001), leading to a target height corrected FH of −0.39 SDS (CI: −0.62 to −0.15) in GHD and −1.22 SDS (CI: −1.57 to −0.87) in SGA (p < 0.001). Girls with GHD had a better long-term outcome, as did boys with SGA when compared to the respective opposite sex. The cut-off of delta height of 0.5 SDS during the first year had a low sensitivity to detect long-term non-responders. We found a relation between short-term and long-term outcomes in GHD but not in SGA (adjusted R2 = 0.66 vs. 0.01). Conclusion: In contrast to GHD, we observed practically no relationship between 1st-year and long-term outcomes in SGA patients treated with GH.
Acceptance of independent curriculum in North Kalimantan
Authors: Setyaningsih Agustina , Bagea Ishak , Mulyadi Mulyadi , Sarip Mohamad , Agustiwi Asri , Mubarok Ence Supriatna , Haetami Aceng
Published: April 2024

Determining the curriculum is the government's authority, in early 2022, the independent curriculum was launched. Implementing an independent curriculum is a challenge in itself for education in North Kalimantan. The reason is educational facilities in this region are not evenly distributed. However, several agencies have made efforts to continue to make the independent curriculum program a success. This research was conducted using the systematic literature review (SLR) method. The results of this research are that the government, teacher groups, and several schools have developed and implemented an independent curriculum. Teaching staff in North Kalimantan experienced various difficulties in implementing the independent curriculum technique, including a lack of resources, such as teaching materials and technology, and confusion due to a lack of understanding. This case is an indication that there is still a need to improve the quality of education, especially in the interior of North Kalimantan.
Teaching proficiency of pre-service secondary teachers in Eastern Samar State University-Salcedo Campus
Authors: Gaganao Rovinson D. , Odon Ma. Gracelda B.
Published: April 2024

Competent teachers are attributed to student performance, school effectiveness, and the efficiency of an entire education system. Hence, this study compares the respondents' teaching proficiency across their profiles and correlates to their academic performance. The study utilized 30 pre-service secondary teachers of Eastern Samar State University Salcedo selected by complete enumeration, a descriptive comparative and correlational research design, and a questionnaire. Frequency, percentage, mean, and standard deviation were applied for descriptive analysis; t-test for comparison of respondents’ teaching proficiency; and Pearson’s correlation coefficient for the relationship between academic performance and teaching proficiency. The study revealed that respondents had a proficient teaching proficiency. Specifically, they were proficient in subject matter knowledge, lesson planning, classroom management, instructional strategies and motivation, communication skills, questioning skills, and professionalism. They have a very good academic performance in both professional education and major field of specialization. Furthermore, the study found no significant difference in the teaching proficiency across the respondents’ sex and age. However, a significant relationship was found between academic performance and teaching proficiency. Based on the findings, it is recommended that remedial classes on contents, pedagogies, and principles be provided especially for those respondents with low academic performance, to improve their teaching proficiency.
Digital students go to campus: did stress and anxiety affect the intention for organization?
Authors: Panduwiyasa Haryasena , Wibowo Ferdian Surya
Published: April 2024

The study delves into the behavioral shifts observed in "digital students" transitioning from distance to onsite learning during the Generation Z era, influenced significantly by the disruptive effects of the COVID-19 pandemic. Technological advancements have reshaped students' perspectives, rendering educational and organizational engagements more accessible via platforms like video conferencing. However, the return to onsite learning has prompted a notable culture shock, leading to heightened levels of stress and anxiety among digital students. This research aims to examine the psychological ramifications of stress and anxiety on post-pandemic student attitudes toward extracurricular organizational intention. Employing the depression anxiety stress scale (DASS-42) and conducting multiple linear regression analysis on a sample of 420 respondents, the study reveals a significant negative impact of stress level (-35.6%) on students' intentions to engage in organizational activities. Additionally, anxiety levels contribute to a variation of -6.8%. These findings underscore the intricate relationship between psychological factors and student participation, underscoring the imperative to address stress and anxiety to foster robust involvement in campus organizational endeavors.
A marcha para o azul
Authors: Lenharo Alcir
Published: April 2024

The dictatorial policy of the Estado Novo made large use of the myth-lemma “Marcha para Oeste” as a factor of social mobilization for the conquest of the Brazilian hinterland. This was not a mere ideological ruse. Its mythical content was retrieved from cherished traditions of the nation’s cultural imagery. It was employed in political terms of order to back up the colonization practice of the regime.
Política e imprensa: alguns exemplos em 1928
Authors: Vesentini Carlos Alberto
Published: April 2024

In order to point out a problem of historical documentation, the author examines some newspapers of 1928. specifically chosen for this purpose. These press organs convey “revolutionists” as well as “revolution” as a universe of force (a form to be given to politics). In this sense such newspapers may be considered as consubstantiating political practice. When they are seen only as sources, this practice is not completed at a given moment, but projects into the present.
A vida política no estado do Amazonas (1910-1924)
Authors: Santos Eloina Monteiro dos
Published: April 2024

This paper refers to the political life of Amazonas State  (1910-1924).
As Devassas eclesiásticas da arquidiocese de Mariana: fonte primária para a história das mentalidades
Authors: Souza Laura de Mello e
Published: April 2024

Records of ecclesiastical lawsuits ("devassas”) constitute an important set of documents, which can largely contribute to the study of the daily life of the populations of the Brazilian State of Minas Gerais during the XVIII century.
No interior da moradia operária São Paulo - 1890/1940
Authors: Decca Maria A. Guzzo
Published: April 2024

This work describles, in general lines, the conditions of the urban proletariat, from the end of XIX century until the begining decades of the XX century, in São Paulo.
Xenartros e Marsupiais do Estado de São Paulo
Authors: Vieira C.
Published: April 2024

Continuando a revisão das varias ordens dos mamíferos ate agora encontrados dentro dos limites do Estado de São Paulo, tratamos aqui dos Xenartros (tatus, tamanduás e preguiças) e dos Marsupials (gambas e cuícas). São os Xenartros uma ordem quase exclusivamente sul-americana, bem representada no Estado de São Paulo, onde, sobretudo os tatus, são muito conhecidos e cágados por toda a parte. O mesmo porem não acontece com a maioria dos Marsupials, dos quais, a não ser os gambas, habituais moradores dos centros povoados, as restantes minúsculas espécies são pouco conhecidas pelas populações rurais do interior que, em geral, as confunde com os ratos. Como nas revisões precedentes, (1) tomamos por base a coleção de peles e crânios atualmente existente no Departamento de Zoologia, redescrevendo várias espécies e subéspecies e atualizando, na medida do possível, a nomenclatura.
Comentários sobre os mamíferos Descritos e Figurados por Alexandre Rodrigues Ferreira em 1790
Authors: Carvalho Cory T. de
Published: April 2024

Alexandre Rodrigues Ferreira (1756-1815), o primeiro zoólogo nascido no Brasil, que reuniu importantes coleções e sobre elas escreveu trabalhos de bastante mérito para o seu tempo, não teve a sorte de os ver publicados em vida. Seus manuscritos foram depositados inicialmente no Real Museu de Lisboa, onde permaneceram desconhecidos, e daí vieram ter ao Rio de Janeiro em 1842, graças a entendimentos havidos entre os governos de Portugal e Brasil. Alguns dos trabalhos foram então publicados em diversas revistas. Alguns desenhos foram copiados em cor no Real Jardim Botânico de Portugal, para o Museu Nacional do Rio de Janeiro, e aqui identificados por E. Goeldi (1886). Por outro lado, parte dos manuscritos e coleções, conservados em Lisboa, foram levadas para o Museu de Paris como presa de guerra por Étienne Geoffroy Saint-Hilaire em 1808. Ali, muitos dos exemplares serviram para descrições do próprio Étienne (1812). de Desmarest & Blainville (1817), Isidore Geoffroy (1844), etc. Em 1934 foi publicado mais um MS original, as Observações geraes e Particulares sobre a Classe dos Mammaes, observados nos três Rios, das Amazonas, Negro, e da Madeira. Não sendo esta edição acompanhada de notas críticas, resolvemos executar a tarefa. Esta não tem apenas o interesse histórico que logicamente desperta a obra do infortunado bahiano; tem também importância científica, pois sua coleção serviu de base à descrição de inúmeras formas, sobre diversas das quais há incerteza, quando não erros e omissões.
Single-Cell Gene-Regulatory Networks of Advanced Symptomatic Atherosclerosis
Authors: Mocci Giuseppe , Sukhavasi Katyayani , Örd Tiit , Bankier Sean , Singha Prosanta , Arasu Uma Thanigai , Agbabiaje Olayinka Oluwasegun , Mäkinen Petri , Ma Lijiang , Hodonsky Chani J. , Aherrahrou Redouane , Muhl Lars , Liu Jianping , Gustafsson Sonja , Byandelger Byambajav , Wang Ying , Koplev Simon , Lendahl Urban , Owens Gary K. , Leeper Nicholas J. , Pasterkamp Gerard , Vanlandewijck Michael , Michoel Tom , Ruusalepp Arno , Hao Ke , Ylä-Herttuala Seppo , Väli Marika , Järve Heli , Mokry Michal , Civelek Mete , Miller Clint J. , Kovacic Jason C. , Kaikkonen Minna U. , Betsholtz Christer , Björkegren Johan L.M.
Published: April 2024

BACKGROUND:

While our understanding of the single-cell gene expression patterns underlying the transformation of vascular cell types during the progression of atherosclerosis is rapidly improving, the clinical and pathophysiological relevance of these changes remains poorly understood.

METHODS:

Single-cell RNA sequencing data generated with SmartSeq2 (≈8000 genes/cell) in 16 588 single cells isolated during atherosclerosis progression in
Ldlr

−/−

Apob

100/100

mice with human-like plasma lipoproteins and from humans with asymptomatic and symptomatic carotid plaques was clustered into multiple subtypes. For clinical and pathophysiological context, the advanced-stage and symptomatic subtype clusters were integrated with 135 tissue-specific (atherosclerotic aortic wall, mammary artery, liver, skeletal muscle, and visceral and subcutaneous, fat) gene-regulatory networks (GRNs) inferred from 600 coronary artery disease patients in the STARNET (Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task) study.

RESULTS:

Advanced stages of atherosclerosis progression and symptomatic carotid plaques were largely characterized by 3 smooth muscle cells (SMCs), and 3 macrophage subtype clusters with extracellular matrix organization/osteogenic (SMC), and M1-type proinflammatory/Trem2-high lipid-associated (macrophage) phenotypes. Integrative analysis of these 6 clusters with STARNET revealed significant enrichments of 3 arterial wall GRNs: GRN33 (macrophage), GRN39 (SMC), and GRN122 (macrophage) with major contributions to coronary artery disease heritability and strong associations with clinical scores of coronary atherosclerosis severity. The presence and pathophysiological relevance of GRN39 were verified in 5 independent RNAseq data sets obtained from the human coronary and aortic artery, and primary SMCs and by targeting its top-key drivers,
FRZB
and
ALCAM
in cultured human coronary artery SMCs.

CONCLUSIONS:

By identifying and integrating the most gene-rich single-cell subclusters of atherosclerosis to date with a coronary artery disease framework of GRNs, GRN39 was identified and independently validated as being critical for the transformation of contractile SMCs into an osteogenic phenotype promoting advanced, symptomatic atherosclerosis.
Mitochondrial CypD Acetylation Promotes Endothelial Dysfunction and Hypertension
Authors: Dikalova Anna , Fehrenbach Daniel , Mayorov Vladimir , Panov Alexander , Ao Mingfang , Lantier Louise , Amarnath Venkataraman , Lopez Marcos G. , Billings Frederic T. , Sack Michael N. , Dikalov Sergey
Published: April 2024

BACKGROUND:

Nearly half of adults have hypertension, a major risk factor for cardiovascular disease. Mitochondrial hyperacetylation is linked to hypertension, but the role of acetylation of specific proteins is not clear. We hypothesized that acetylation of mitochondrial CypD (cyclophilin D) at K166 contributes to endothelial dysfunction and hypertension.

METHODS:

To test this hypothesis, we studied CypD acetylation in patients with essential hypertension, defined a pathogenic role of CypD acetylation in deacetylation mimetic CypD-K166R mutant mice and endothelial-specific GCN5L1 (general control of amino acid synthesis 5 like 1)–deficient mice using an Ang II (angiotensin II) model of hypertension.

RESULTS:

Arterioles from hypertensive patients had 280% higher CypD acetylation coupled with reduced Sirt3 (sirtuin 3) and increased GCN5L1 levels. GCN5L1 regulates mitochondrial protein acetylation and promotes CypD acetylation, which is counteracted by mitochondrial deacetylase Sirt3. In human aortic endothelial cells, GCN5L1 depletion prevents superoxide overproduction. Deacetylation mimetic CypD-K166R mice were protected from vascular oxidative stress, endothelial dysfunction, and Ang II-induced hypertension. Ang II-induced hypertension increased mitochondrial GCN5L1 and reduced Sirt3 levels resulting in a 250% increase in GCN5L1/Sirt3 ratio promoting CypD acetylation. Treatment with mitochondria-targeted scavenger of cytotoxic isolevuglandins (mito2HOBA) normalized GCN5L1/Sirt3 ratio, reduced CypD acetylation, and attenuated hypertension. The role of mitochondrial acetyltransferase GCN5L1 in the endothelial function was tested in endothelial-specific GCN5L1 knockout mice. Depletion of endothelial GCN5L1 prevented Ang II-induced mitochondrial oxidative stress, reduced the maladaptive switch of vascular metabolism to glycolysis, prevented inactivation of endothelial nitric oxide, preserved endothelial-dependent relaxation, and attenuated hypertension.

CONCLUSIONS:

These data support the pathogenic role of CypD acetylation in endothelial dysfunction and hypertension. We suggest that targeting cytotoxic mitochondrial isolevuglandins and GCN5L1 reduces CypD acetylation, which may be beneficial in cardiovascular disease.
Association Between Hemoglobin A1c and Development of Cardiovascular Disease in Canadian Men and Women Without Diabetes at Baseline: A Population‐Based Study of 608 474 Adults
Authors: Butalia Sonia , Chu Luan Manh , Dover Douglas C. , Lau Darren , Yeung Roseanne O. , Eurich Dean T. , Senior Peter , Kaul Padma
Published: April 2024

Background

We examined the association between hemoglobin A1c (HbA1c) and the development of cardiovascular disease (CVD) in men and women, without diabetes or CVD at baseline.

Methods and Results

This retrospective cohort study included adults aged 40 to <80 years in Alberta, Canada. Men and women were divided into categories based on a random HbA1c during a 3‐year enrollment period. The primary outcome of CVD hospitalization and secondary outcome of combined CVD hospitalization/mortality were examined during a 5‐year follow‐up period until March 31, 2021. A total of 608 474 individuals (55.2% women) were included. Compared with HbA1c 5.0% to 5.4%, men with HbA1c of 5.5% to 5.9% had an increased risk of CVD hospitalization (adjusted hazard ratio [aHR], 1.12 [95% CI, 1.07–1.19]) whereas women did not (aHR, 1.01 [95% CI, 0.95–1.08]). Men and women with HbA1c of 6.0% to 6.4% had a 38% and 17% higher risk and men and women with HbA1c ≥6.5% had a 79% and 51% higher risk of CVD hospitalization, respectively. In addition, HbA1c of 6.0% to 6.4% and HbA1c ≥6.5% were associated with a higher risk (14% and 41%, respectively) of CVD hospitalization/death in men, but HbA1c ≥6.5% was associated with a 24% higher risk only among women.

Conclusions

In both men and women, HbA1c ≥6.0% was associated with an increased risk of CVD and mortality outcomes. The association between CVD and HbA1c levels of 5.5% to 5.9%, considered to be in the “normal” range, highlights the importance of optimizing cardiovascular risk profiles at all levels of glycemia, especially in men.
Impact of Vaccination Status on Outcome of Patients With COVID‐19 and Acute Ischemic Stroke Undergoing Mechanical Thrombectomy
Authors: Deuschl Cornelius , Goertz Lukas , Kabbasch Christoph , Köhrmann Martin , Kleinschnitz Christoph , Berlis Ansgar , Maurer Christoph Johannes , Mühlen Iris , Kallmünzer Bernd , Gawlitza Matthias , Kaiser Daniel P. O. , Klisch Joachim , Lobsien Donald , Behme Daniel , Thormann Maximilian , Flottmann Fabian , Winkelmeier Laurens , Gizewski Elke Ruth , Mayer‐Suess Lukas , Holtmannspoetter Markus , Moenninghoff Christoph , Schlunz‐Hendann Martin , Grieb Dominik , Arendt Christophe T. , Bohmann Ferdinand O. , Altenbernd Jens , Li Yan , Sure Ulrich , Mühl‐Benninghaus Ruben , Rodt Thomas , Kallenberg Kai , Durutya Alexandru , Elsharkawy Mohamed , Stracke Christian‐Paul , Schumann Mathias Gerhard , Bock Alexander , Nikoubashman Omid , Wiesmann Martin , Henkes Hans , Dolff Sebastian , Demircioglu Aydin , Forsting Michael , Styczen Hanna
Published: April 2024

Background

Data on impact of COVID‐19 vaccination and outcomes of patients with COVID‐19 and acute ischemic stroke undergoing mechanical thrombectomy are scarce. Addressing this subject, we report our multicenter experience.

Methods and Results

This was a retrospective analysis of patients with COVID‐19 and known vaccination status treated with mechanical thrombectomy for acute ischemic stroke at 20 tertiary care centers between January 2020 and January 2023. Baseline demographics, angiographic outcome, and clinical outcome evaluated by the modified Rankin Scale score at discharge were noted. A multivariate analysis was conducted to test whether these variables were associated with an unfavorable outcome, defined as modified Rankin Scale score >3. A total of 137 patients with acute ischemic stroke (48 vaccinated and 89 unvaccinated) with acute or subsided COVID‐19 infection who underwent mechanical thrombectomy attributable to vessel occlusion were included in the study. Angiographic outcomes between vaccinated and unvaccinated patients were similar (modified Thrombolysis in Cerebral Infarction ≥2b: 85.4% in vaccinated patients versus 86.5% in unvaccinated patients;
P
=0.859). The rate of functional independence (modified Rankin Scale score, ≤2) was 23.3% in the vaccinated group and 20.9% in the unvaccinated group (
P
=0.763). The mortality rate was 30% in both groups. In the multivariable analysis, vaccination status was not a significant predictor for an unfavorable outcome (
P
=0.957). However, acute COVID‐19 infection remained significant (odds ratio, 1.197 [95% CI, 1.007–1.417];
P
=0.041).

Conclusions

Our study demonstrated no impact of COVID‐19 vaccination on angiographic or clinical outcome of COVID‐19–positive patients with acute ischemic stroke undergoing mechanical thrombectomy, whereas worsening attributable to COVID‐19 was confirmed.
Impact of New‐Onset Right Bundle‐Branch Block After Transcatheter Aortic Valve Replacement on Permanent Pacemaker Implantation
Authors: Kikuchi Shinnosuke , Minamimoto Yugo , Matsushita Kensuke , Cho Tomoki , Terasaka Kengo , Hanajima Yohei , Nakahashi Hidefumi , Gohbara Masaomi , Kimura Yuichiro , Yasuda Shota , Okada Kozo , Matsuzawa Yasushi , Iwahashi Noriaki , Kosuge Masami , Ebina Toshiaki , Morel Olivier , Ohlmann Patrick , Uchida Keiji , Hibi Kiyoshi
Published: April 2024

Background

A delayed and recurrent complete atrioventricular block (CAVB) is a life‐threatening complication of transcatheter aortic valve replacement (TAVR). Post‐TAVR evaluation may be important in predicting delayed and recurrent CAVB requiring permanent pacemaker implantation (PPI). The impact of new‐onset right bundle‐branch block (RBBB) after TAVR on PPI remains unknown.

Methods and Results

In total, 407 patients with aortic stenosis who underwent TAVR were included in this analysis. Intraprocedural CAVB was defined as CAVB that occurred during TAVR. A 12‐lead ECG was evaluated at baseline, immediately after TAVR, on postoperative days 1 and 5, and according to the need to identify new‐onset bundle‐branch block (BBB) and CAVB after TAVR. Forty patients (9.8%) required PPI, 17 patients (4.2%) had persistent intraprocedural CAVB, and 23 (5.7%) had delayed or recurrent CAVB after TAVR. The rates of no new‐onset BBB, new‐onset left BBB, and new‐onset RBBB were 65.1%, 26.8%, and 4.7%, respectively. Compared with patients without new‐onset BBB and those with new‐onset left BBB, the rate of PPI was higher in patients with new‐onset RBBB (3.4% versus 5.6% versus 44.4%,
P
<0.0001). On post‐TAVR evaluation in patients without persistent intraprocedural CAVB, the multivariate logistic regression analysis showed that new‐onset RBBB was a statistically significant predictor of PPI compared with no new‐onset BBB (odds ratio [OR], 18.0 [95% CI, 5.94–54.4]) in addition to the use of a self‐expanding valve (OR, 2.97 [95% CI, 1.09–8.10]).

Conclusions

Patients with new‐onset RBBB after TAVR are at high risk for PPI.