bluuebunny/crossref_metadata_2025 huggingface dataset:
Muscle biopsy long-chain omega-3 polyunsaturated fatty acid compositions, IMF and FMP in Australian pasture-based Bowen Genetics Forest Pastoral Angus, Hereford, and Wagyu Beef Cattle
Authors: Otto John Roger , Mwangi Felista Waithira , Pewan Shedrach Benjamin , Adegboye Oyelola Abdulwasiu , Malau-Aduli Aduli Enoch Othniel
Published: March 2024

Background

We investigated breed and gender variations in the compositions of long-chain (≥ C20) omega-3 polyunsaturated fatty acids (LC omega-3 PUFA), fat melting point (FMP) and intramuscular fat (IMF) contents in biopsy samples of the M. longissimus dorsi muscle of grazing beef cattle. The hypothesis that biopsy compositions of health-beneficial LC omega-3 PUFA, FMP and IMF in a pasture-based production system will vary with breed, was tested. Muscle biopsies were taken from 127 yearling pasture-based Angus, Hereford, and Wagyu heifers and young bulls exclusive to the Australian Bowen Genetics Forest Pastoral breeding stud averaging 12 ± 2.43 months of age and under the same management routine.

Results

Breed had a significant influence on IMF, FMP, and the compositions of oleic acid, α-linolenic acid (ALA), eicosapentaenoic (EPA), docosahexaenoic (DHA), docosapentaenoic (DPA), and total EPA + DHA + DPA in the M. longissimus dorsi muscle biopsies (P ≤ 0.03). The Wagyu breed had the highest (11.1%) and Hereford the lowest (5.9%) IMF (P = 0.03). The reverse trend was observed in FMP values where the Hereford breed had the highest (55 °C), Angus intermediate (46.5 °C), and Wagyu the lowest (33 °C) FMP. The Wagyu and Angus breeds had similar oleic fatty acid (18:1n-9) content, while the Hereford breed had the lowest (P < 0.01). The highest ALA, DPA, total EPA + DHA, total EPA + DHA + DPA and total ALA + EPA + DHA + DPA contents were detected in the Wagyu breed (P ≤ 0.03). The Hereford had similar EPA and DPA contents to the Angus (P ≥ 0.46). Total EPA + DHA + DPA contents in Wagyu, Angus, and Hereford were 28.8, 21.5, and 22.1 mg/100g tissue (P = 0.01), respectively. Sex was an important source of variation that influenced LC omega-3 PUFA composition, FMP and IMF, where yearling heifers had higher IMF (11.9% vs 5.3%), lower FMP (33°C vs 37°C), and higher LC omega-3 PUFA than bulls.

Conclusion

All the results taken together indicate that the Wagyu breed at 28.8 mg/100g tissue, was the closest to meeting the Australia and New Zealand recommended source level threshold of 30 mg/100g tissue of health-beneficial ≥ C20 omega-3 FA content. Since gender was a significant determinant of LC omega-3 PUFA composition, IMF content and FMP, it should be factored into enhancement strategies of healthy meat eating quality traits in grazing cattle. These findings also suggest that the Bowen Genetics Forest Pastoral beef cattle studs are important sources of LC omega-3 PUFA that can be used to cover the deficit in these health claimable fatty acids in Western diets.
Reproducible isolation of bovine mammary macrophages for analysis of host pathogen interactions
Authors: Tomes Abbie , Archer Nathan , Leigh James
Published: March 2024

Background

Macrophages residing in milk are vital during intramammary infections. This study sought to develop a method enabling the investigation of macrophage responses to pathogens. Streptococcus uberis is the predominant cause of bovine mastitis UK-wide and its pathogenesis is unusual compared to other intramammary pathogens. Previous studies utilise macrophage cell lines, isolated bovine blood derived monocytes, or macrophages from raw milk through complex or inconsistent strategies such as fluorescence activated cell sorting (FACS), centrifugation and selective adherence, and CD14 antibody-microbeads. The centrifuge steps required in the initial stages often damage cells. Thus, the aim of this study was to develop a reliable, reproducible, and cost-effective method for isolating mammary macrophages from milk in a way that allows their culture, challenge with bacteria, and measurement of their response ex-vivo.

Results

This method achieves an average yield of 1.27 × 107 cells per litre of milk. Whole milk with somatic cell range of 45–65 cells/µL produced excellent yields, with efficient isolations accomplished with up to 150 cells/µL. This strategy uses milk diluted in PAE buffer to enable low-speed centrifugation steps followed by seeding on tissue-culture-treated plastic. Seeding 1,000,000 milk-extracted cells onto tissue culture plates was sufficient to obtain 50,000 macrophage. Isolated macrophage remained responsive to challenge, with the highest concentration of IL-1β measured by ELISA at 20 h after challenge with S. uberis. In this model, the optimal multiplicity of infection was found to be 50:1 bacteria:macrophage. No difference in IL-1β production was found between macrophages challenged with live or heat-killed S. uberis. Standardisation of the production of IL-1β to that obtained following macrophage stimulation with LPS allowed for comparisons between preparations.

Conclusions

A cost-effective method, utilising low-speed centrifugation followed by adherence to plastic, was established to isolate bovine mammary macrophages from raw milk. This method was shown to be appropriate for bacterial challenge, therefore providing a cost-effective, ex-vivo, and non-invasive model of macrophage-pathogen interactions. The optimal multiplicity of infection for S. uberis challenge was demonstrated and a method for standardisation against LPS described which removes sample variation. This robust method enables, reproducible and reliable interrogation of critical pathogen-host interactions which occur in the mammary gland.
Association between serum 25-hydroxyvitamin D and vitamin D dietary supplementation and risk of all-cause and cardiovascular mortality among adults with hypertension
Authors: Ye Haowen , Li Yexin , Liu Shaomin , Zhang Xiaofang , Liang Huanzhu , Wang Ying , Wang Ruxin , Liu Han , Wen Yun , Jing Chunxia , Wang Lihong
Published: March 2024

Background

The relationship between vitamin D status and mortality among adults with hypertension remains unclear.

Methods

This prospective cohort study involved a sample of 19,500 adults with hypertension who participated in the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2018. We utilized a weighted COX proportional hazard model to assess the association between vitamin D status and mortality. This statistical model calculates hazard ratios (HR) and their corresponding 95% confidence intervals (95% CI).

Results

The study indicated that lower serum 25(OH)D concentration was associated with an increased risk of all-cause mortality among individuals with hypertension. Specially. Those with concentrations between 25.0 and 49.9 nmol/L (HR = 1.71, 95%CI = 1.22–2.40) and less than 25.0 nmol/L (HR = 1.97, 95%CI = 1.15–3.39) had higher hazard ratios for all-cause mortality. Individuals with hypertension who took vitamin D supplements had a lower risk of all-cause mortality, but not the risk of CVD mortality (HR 0.75, 95%CI 0.54–1.03), compared to those who did not supplement (HR = 0.76, 95%CI = 0.61–0.94). Subgroup analysis further revealed that vitamin D supplementation was associated with a reduced risk of all-cause mortality among individuals without diabetes (HR = 0.65, 95%CI = 0.52–0.81) and individuals without CVD (HR = 0.75, 95%CI = 0.58–0.97), and a decreased risk of CVD mortality among individuals without diabetes (HR = 0.63, 95%CI = 0.45–0.88) and without CVD (HR = 0.61, 95%CI = 0.40–0.92). Furthermore, higher-dose vitamin D supplementation was also associated with a greater reduction in all-cause mortality among hypertensive individuals, and there was the potential synergistic effect of combining normal-dose calcium and vitamin D supplementation, showing a superior effect on mortality compared to low-dose supplementation in adults with hypertension.

Conclusions

This prospective cohort study demonstrated a significant association between lower serum 25 (OH)D concentration and increased all-cause mortality among adults with hypertension. Furthermore, the study found that vitamin D supplementation had a strong and significantly positive correlation with reduced all-cause and CVD mortality among hypertensive individuals without diabetes or CVD. This positive correlation suggests that vitamin D supplementation could potentially be an effective strategy to reduce the risk of mortality in this specific group of people.
Integration of pan-omics technologies and three-dimensional in vitro tumor models: an approach toward drug discovery and precision medicine
Authors: Jose Anmi , Kulkarni Pallavi , Thilakan Jaya , Munisamy Murali , Malhotra Anvita Gupta , Singh Jitendra , Kumar Ashok , Rangnekar Vivek M. , Arya Neha , Rao Mahadev
Published: March 2024

Despite advancements in treatment protocols, cancer is one of the leading cause of deaths worldwide. Therefore, there is a need to identify newer and personalized therapeutic targets along with screening technologies to combat cancer. With the advent of pan-omics technologies, such as genomics, transcriptomics, proteomics, metabolomics, and lipidomics, the scientific community has witnessed an improved molecular and metabolomic understanding of various diseases, including cancer. In addition, three-dimensional (3-D) disease models have been efficiently utilized for understanding disease pathophysiology and as screening tools in drug discovery. An integrated approach utilizing pan-omics technologies and 3-D in vitro tumor models has led to improved understanding of the intricate network encompassing various signalling pathways and molecular cross-talk in solid tumors. In the present review, we underscore the current trends in omics technologies and highlight their role in understanding genotypic-phenotypic co-relation in cancer with respect to 3-D in vitro tumor models. We further discuss the challenges associated with omics technologies and provide our outlook on the future applications of these technologies in drug discovery and precision medicine for improved management of cancer.

Graphical Abstract
Bladder-cancer-derived exosomal circRNA_0013936 promotes suppressive immunity by up-regulating fatty acid transporter protein 2 and down-regulating receptor-interacting protein kinase 3 in PMN-MDSCs
Authors: Shi Xiaojun , Pang Shiyu , Zhou Jiawei , Yan Guang , Gao Ruxi , Wu Haowei , Wang Zhou , Wei Yuqing , Liu Xinyu , Tan Wanlong
Published: March 2024

Background

Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) is one of the causes of tumor immune tolerance and failure of cancer immunotherapy. Here, we found that bladder cancer (BCa)-derived exosomal circRNA_0013936 could enhance the immunosuppressive activity of PMN-MDSCs by regulating the expression of fatty acid transporter protein 2 (FATP2) and receptor-interacting protein kinase 3 (RIPK3). However, the underlying mechanism remains largely unknown.

Methods

BCa-derived exosomes was isolated and used for a series of experiments. RNA sequencing was used to identify the differentially expressed circRNAs. Western blotting, immunohistochemistry, immunofluorescence, qRT-PCR, ELISA and Flow cytometry were performed to reveal the potential mechanism of circRNA_0013936 promoting the immunosuppressive activity of PMN-MDSC.

Results

CircRNA_0013936 enriched in BCa-derived exosomes could promote the expression of FATP2 and inhibit the expression of RIPK3 in PMN-MDSCs. Mechanistically, circRNA_0013936 promoted the expression of FATP2 and inhibited the expression of RIPK3 expression via sponging miR-320a and miR-301b, which directly targeted JAK2 and CREB1 respectively. Ultimately, circRNA_0013936 significantly inhibited the functions of CD8+ T cells by up-regulating FATP2 through the circRNA_0013936/miR-320a/JAK2 pathway, and down-regulating RIPK3 through the circRNA_0013936/miR-301b/CREB1 pathway in PMN-MDSCs.

Conclusions

BCa-derived exosomal circRNA_0013936 promotes suppressive immunity by up-regulating FATP2 through the circRNA_0013936/miR-320a/JAK2 pathway and down-regulating RIPK3 through the circRNA_0013936/miR-301b-3p/CREB1 pathway in PMN-MDSCs. These findings help to find new targets for clinical treatment of human bladder cancer.
Tumor acidification and GSH depletion by bimetallic composite nanoparticles for enhanced chemodynamic therapy of TNBC
Authors: Chen Wenting , Hu Fangfang , Gao Qian , Zheng Caiyun , Bai Que , Liu Jinxi , Sun Na , Zhang Wenhui , Zhang Yanni , Dong Kai , Lu Tingli
Published: March 2024

Chemodynamic therapy (CDT) based on intracellular Fenton reaction to produce highly cytotoxic reactive oxygen species (ROS) has played an essential role in tumor therapy. However, this therapy still needs to be improved by weakly acidic pH and over-expression of glutathione (GSH) in tumor microenvironment (TEM), which hinders its future application. Herein, we reported a multifunctional bimetallic composite nanoparticle MnO2@GA-Fe@CAI based on a metal polyphenol network (MPN) structure, which could reduce intracellular pH and endogenous GSH by remodeling tumor microenvironment to improve Fenton activity. MnO2 nanoparticles were prepared first and MnO2@GA-Fe nanoparticles with Fe3+ as central ion and gallic acid (GA) as surface ligands were prepared by the chelation reaction. Then, carbonic anhydrase inhibitor (CAI) was coupled with GA to form MnO2@GA-Fe@CAI. The properties of the bimetallic composite nanoparticles were studied, and the results showed that CAI could reduce intracellular pH. At the same time, MnO2 could deplete intracellular GSH and produce Mn2+ via redox reactions, which re-established the TME with low pH and GSH. In addition, GA reduced Fe3+ to Fe2+. Mn2+ and Fe2+ catalyzed the endogenous H2O2 to produce high-lever ROS to kill tumor cells. Compared with MnO2, MnO2@GA-Fe@CAI could reduce the tumor weight and volume for the xenograft MDA-MB-231 tumor-bearing mice and the final tumor inhibition rate of 58.09 ± 5.77%, showing the improved therapeutic effect as well as the biological safety. Therefore, this study achieved the high-efficiency CDT effect catalyzed by bimetallic through reshaping the tumor microenvironment.

Graphical Abstract
Enabling the examination of long-term mortality trends by educational level for England and Wales in a time-consistent and internationally comparable manner
Authors: Janssen Fanny , Van Hemelrijck Wanda , Kagenaar Eva , Sizer Alison
Published: March 2024

Background

Studying long-term trends in educational inequalities in health is important for monitoring and policy evaluation. Data issues regarding the allocation of people to educational groups hamper the study and international comparison of educational inequalities in mortality. For the UK, this has been acknowledged, but no satisfactory solution has been proposed.

Objective

To enable the examination of long-term mortality trends by educational level for England and Wales (E&W) in a time-consistent and internationally comparable manner, we propose and implement an approach to deal with the data issues regarding mortality data by educational level.

Methods

We employed 10-year follow-ups of individuals aged 20+ from the Office for National Statistics Longitudinal Study (ONS-LS), which include education information from each decennial census (1971–2011) linked to individual death records, for a 1% representative sample of the E&W population. We assigned the individual cohort data to single ages and calendar years, and subsequently obtained aggregate all-cause mortality data by education, sex, age (30+), and year (1972–2017). Our data adjustment approach optimised the available education information at the individual level, and adjusts—at the aggregate level—for trend discontinuities related to the identified data issues, and for differences with country-level mortality data for the total population.

Results

The approach resulted in (1) a time-consistent and internationally comparable categorisation of educational attainment into the low, middle, and high educated; (2) the adjustment of identified data-quality related discontinuities in the trends over time in the share of personyears and deaths by educational level, and in the crude and the age-standardised death rate by and across educational levels; (3) complete mortality data by education for ONS-LS members aged 30+ in 1972–2017 which aligns with country-level mortality data for the total population; and (4) the estimation of inequality measures using established methods. For those aged 30+ , both absolute and relative educational inequalities in mortality first increased and subsequently decreased.

Conclusion

We obtained additional insights into long-term trends in educational inequalities in mortality in E&W, and illustrated the potential effects of different data issues. We recommend the use of (part of) the proposed approach in other contexts.
The role of macrophage polarization and cellular crosstalk in the pulmonary fibrotic microenvironment: a review
Authors: Zhou Bo-wen , Liu Hua-man , Xu Fei , Jia Xin-hua
Published: March 2024

Pulmonary fibrosis (PF) is a progressive interstitial inflammatory disease with a high mortality rate. Patients with PF commonly experience a chronic dry cough and progressive dyspnoea for years without effective mitigation. The pathogenesis of PF is believed to be associated with dysfunctional macrophage polarization, fibroblast proliferation, and the loss of epithelial cells. Thus, it is of great importance and necessity to explore the interactions among macrophages, fibroblasts, and alveolar epithelial cells in lung fibrosis, as well as in the pro-fibrotic microenvironment. In this review, we discuss the latest studies that have investigated macrophage polarization and activation of non-immune cells in the context of PF pathogenesis and progression. Next, we discuss how profibrotic cellular crosstalk is promoted in the PF microenvironment by multiple cytokines, chemokines, and signalling pathways. And finally, we discuss the potential mechanisms of fibrogenesis development and efficient therapeutic strategies for the disease. Herein, we provide a comprehensive summary of the vital role of macrophage polarization in PF and its profibrotic crosstalk with fibroblasts and alveolar epithelial cells and suggest potential treatment strategies to target their cellular communication in the microenvironment.
Serum and salivary inflammatory biomarkers in juvenile idiopathic arthritis—an explorative cross-sectional study
Authors: Cetrelli Lena , Lundestad Anette , Gil Elisabet G. , Fischer Johannes , Halbig Josefine , Frid Paula , Angenete Oskar , Rosén Annika , Tylleskär Karin B. , Luukko Keijo , Nordal Ellen , Åstrøm Anne N. , Skeie Marit S. , Stunes Astrid Kamilla , Bletsa Athanasia , Sen Abhijit , Feuerherm Astrid J. , Rygg Marite
Published: March 2024

Background

Biomarkers may be useful in monitoring disease activity in juvenile idiopathic arthritis (JIA). With new treatment options and treatment goals in JIA, there is an urgent need for more sensitive and responsive biomarkers.

Objective

We aimed to investigate the patterns of 92 inflammation-related biomarkers in serum and saliva in a group of Norwegian children and adolescents with JIA and controls and in active and inactive JIA. In addition, we explored whether treatment with tumor necrosis factor inhibitors (TNFi) affected the biomarker levels.

Methods

This explorative, cross-sectional study comprised a subset of children and adolescents with non-systemic JIA and matched controls from the Norwegian juvenile idiopathic arthritis study (NorJIA Study). The JIA group included individuals with clinically active or inactive JIA. Serum and unstimulated saliva were analyzed using a multiplex assay of 92 inflammation-related biomarkers. Welch’s t-test and Mann–Whitney U-test were used to analyze the differences in biomarker levels between JIA and controls and between active and inactive disease.

Results

We included 42 participants with JIA and 30 controls, predominantly females, with a median age of 14 years. Of the 92 biomarkers, 87 were detected in serum, 73 in saliva, and 71 in both biofluids. A pronounced difference between serum and salivary biomarker patterns was found. Most biomarkers had higher levels in serum and lower levels in saliva in JIA versus controls, and in active versus inactive disease. In serum, TNF and S100A12 levels were notably higher in JIA and active disease. The TNF increase was less pronounced when excluding TNFi-treated individuals. In saliva, several biomarkers from the chemokine family were distinctly lower in the JIA group, and levels were even lower in active disease.

Conclusion

In this explorative study, the serum and salivary biomarker patterns differed markedly, suggesting that saliva may not be a suitable substitute for serum when assessing systemic inflammation in JIA. Increased TNF levels in serum may not be a reliable biomarker for inflammatory activity in TNFi-treated children and adolescents with JIA. The lower levels of chemokines in saliva in JIA compared to controls and in active compared to inactive disease, warrant further investigation.
Two lymphoma histotypes and papillary thyroid carcinoma coexisting on Hashimoto ground: a case report and review of the literature
Authors: Iskra Igor , Tomaš Maja Ilić , Crnčić Tatjana Bogović , Kukić Edvin , Hadžisejdić Ita , Avirović Manuela , Girotto Neva
Published: March 2024

Background

Papillary carcinoma is the most frequent type of thyroid carcinoma, while primary thyroid lymphoma is uncommon disease. The coexistence of these entities has already been described, and the common risk factor is considered Hashimoto thyroiditis. The two most frequent histotypes of primary thyroid lymphoma are diffuse large B-cell and mucosa-associated lymphoid tissue lymphoma, but the coexistence of both with papillary carcinoma is rarely reported.

Methods

We present a case of a previously healthy 57-years old male with rapidly growing lump on the right side of the neck. Ultrasonography revealed nodules in both thyroid lobes. Fine needle aspiration cytology and pertechnetate scintigraphy were performed. Due to the Bethesda T-5 in the “cold” nodule of the right lobe, surgery with histopathological and immunohistochemistry analysis was indicated.

Results

Histopathological and immunohistochemistry methods confirmed concomitant malignancies in the thyroid gland: diffuse large B-cell lymphoma and papillary carcinoma in the right, and mucosa-associated lymphoid tissue lymphoma in the left lobe with Hashimoto thyroiditis in the remaining tissue. Patient underwent therapy procedures and was without signs of local recurrence or metastatic spread on subsequent follow-up.

Conclusions

Sudden appearance of the neck mass in patients with Hashimoto thyroiditis should raise suspicion on primary thyroid lymphoma and be promptly taken in the diagnostic workup, including fine needle aspiration cytology. Pathology with immunohistochemistry is crucial for further clinical decision making. Since the standardized protocol in management of these complex patients is missing, personal approach and close collaboration between cytologist, pathologist, surgeon, haematologist and nuclear medicine specialist is essential.
Vascular covered stent and video-assisted thoracoscopic surgery for Aortoesophageal fistula caused by esophageal fishbone: a case report
Authors: Chen Jianfeng
Published: March 2024

Background

Aortoesophageal fistula (AEF) is a rare condition characterized by communication between the aorta and esophagus. AEF caused by an esophageal foreign body is even rare, and there is currently no recommended standard treatment protocol. We report a case of delayed aortic rupture after the endoscopic removal of a fish bone, which was successfully treated with a combined approach of vascular stenting and thoracic surgery.

Case presentation

A 33-year-old man presented to the hospital after experiencing chest discomfort for 3 days following the accidental ingestion of a fish bone. Under endoscopic guidance, the fish bone was successfully removed, and the patient was subsequently admitted for medical therapy. On the fourth postoperative day, the patient suddenly developed hematemesis, and chest computed tomography angiography revealed the presence of an AEF. This necessitated urgent intervention; hence, thoracic surgery was performed and a vascular-covered stent was placed. Following the surgical procedure, the patient received active medical treatment, recovered well, and was successfully discharged from the hospital.

Conclusions

In patients with esophageal perforation caused by foreign bodies, hospitalization for observation, computed tomography angiography examination, early use of antibiotics, and careful assessment of aortic damage are advised. Thoracic endovascular aortic repair and esophageal rupture repair may have benefits for the treatment of AEF.
TRF2 as novel marker of tumor response to taxane-based therapy: from mechanistic insight to clinical implication
Authors: Iachettini Sara , Terrenato Irene , Porru Manuela , Di Vito Serena , Rizzo Angela , D’Angelo Carmen , Petti Eleonora , Dinami Roberto , Maresca Carmen , Di Benedetto Anna , Palange Aldo , Mulè Antonino , Santoro Angela , Palazzo Antonella , Fuso Paola , Stoppacciaro Antonella , Vici Patrizia , Filomeno Lorena , Di Lisa Francesca Sofia , Arcuri Teresa , Krasniqi Eriseld , Fabi Alessandra , Biroccio Annamaria , Zizza Pasquale
Published: March 2024

Background

Breast Cancer (BC) can be classified, due to its heterogeneity, into multiple subtypes that differ for prognosis and clinical management. Notably, triple negative breast cancer (TNBC) – the most aggressive BC form – is refractory to endocrine and most of the target therapies. In this view, taxane-based therapy still represents the elective strategy for the treatment of this tumor. However, due variability in patients’ response, management of TNBC still represents an unmet medical need.

Telomeric Binding Factor 2 (TRF2), a key regulator of telomere integrity that is over-expressed in several tumors, including TNBC, has been recently found to plays a role in regulating autophagy, a degradative process that is involved in drug detoxification.

Based on these considerations, we pointed, here, at investigating if TRF2, regulating autophagy, can affect tumor sensitivity to therapy.

Methods

Human TNBC cell lines, over-expressing or not TRF2, were subjected to treatment with different taxanes and drug efficacy was tested in terms of autophagic response and cell proliferation. Autophagy was evaluated first biochemically, by measuring the levels of LC3, and then by immunofluorescence analysis of LC3-puncta positive cells. Concerning the proliferation, cells were subjected to colony formation assays associated with western blot and FACS analyses. The obtained results were then confirmed also in mouse models. Finally, the clinical relevance of our findings was established by retrospective analysis on a cohort of TNBC patients subjected to taxane-based neoadjuvant chemotherapy.

Results

This study demonstrated that TRF2, inhibiting autophagy, is able to increase the sensitivity of TNBC cells to taxanes. The data, first obtained in in vitro models, were then recapitulated in preclinical mouse models and in a cohort of TNBC patients, definitively demonstrating that TRF2 over-expression enhances the efficacy of taxane-based neoadjuvant therapy in reducing tumor growth and its recurrence upon surgical intervention.

Conclusions

Based on our finding it is possible to conclude that TRF2, already known for its role in promoting tumor formation and progression, might represents an Achilles’ heel for cancer. In this view, TRF2 might be exploited as a putative biomarker to predict the response of TNBC patients to taxane-based neoadjuvant chemotherapy.
LATS2 degradation promoted fibrosis damage and rescued by vitamin K3 in lupus nephritis
Authors: Cheng Chen , Yang Hao , Yang Chan , Xie Juan , Wang Jinshen , Cheng Luping , He Jianfu , Li Honglian , Yuan Haoxing , Guo Fangfang , Li Minmin , Liu Shuwen
Published: March 2024

Background

Lupus nephritis (LN) is the most common complication of systemic lupus erythematosus (SLE). The limited treatment options for LN increase the economic burdens on patients. Because fibrotic progression leads to irreversible renal damage in LN patients and further progresses to chronic kidney disease (CKD) and the end stage of renal disease (ESRD), developing new targets to prevent LN fibrotic progression could lead to a feasible treatment strategy for LN patients.

Methods

In this study, we examined YAP activation and LATS2 downregulation in LN kidney biopsy samples (LN: n = 8, normal: n = 2) and lupus-prone MRL/lpr mice (n = 8 for each disease stage). The function of LATS2 was further investigated by in situ injection of Ad-LATS2 into mice with LN (n = 6 mice per group). We examined the role of SIAH2-LATS2 regulation by IP-MS and co-IP, and the protective effect of the SIAH2 inhibitor was investigated in mice with LN.

Results

Restoring LATS2 by an adenovirus in vivo alleviated renal fibrotic damage in mice with LN. Moreover, we found that LATS2 was degraded by a K48 ubiquitination-proteasome pathway mediated by SIAH2 and promoted YAP activation to worsen fibrosis progression in LN. The H150 region of the substrate binding domain (SBD) is an important site for SIAH2-LATS2 binding. The SIAH2-specific inhibitor vitamin K3 protected against LN-associated fibrotic damage in vivo.

Conclusion

In summary, we identified the SIAH2-LATS2 axis as an attractive intervention target in LN to alter the resistance to fibrosis.
Effect of remission, clinical remission with active serology, and glucocorticoid dosage on the pregnancy outcome of pregnant patients with systemic lupus erythematosus
Authors: Nakai Takehiro , Honda Nanase , Soga Eri , Fukui Sho , Kitada Ayako , Yokogawa Naoto , Okada Masato
Published: March 2024

Background

Remission is a key treatment target in systemic lupus erythematosus (SLE) management. Given the direct correlation between lupus flares and elevated risks of adverse pregnancy outcomes (APOs), securing remission before conception becomes crucial. However, the association between clinical remission with active serology, and the risk of APOs is not thoroughly understood. Additionally, determining the optimal glucocorticoid dosage during pregnancy to mitigate APO risks remains under-researched. This study investigated the risk of APOs in relation to remission/serological activity status in patients in clinical remission/glucocorticoid dosage.

Methods

Pregnant patients with SLE, who were followed up at two Japanese tertiary referral centers, and had their remission status assessed at conception, were included in this study. We categorized the patients into two groups based on whether they achieved Zen/Doria remission at conception and analyzed the APO ratio. We also examined the influence of serological activity in pregnant patients with clinical remission and analyzed the optimal glucocorticoid dosage to minimize the APO ratio.

Results

Of the 96 pregnancies included, 59 achieved remission at conception. Pregnant patients who achieved remission showed a significant decrease in the APO ratio compared with those who did not. (overall APO: odds ratio (OR) 0.27, 95% confidence interval (CI) 0.11–0.65, p < 0.01, maternal APO: OR 0.34, 95%CI 0.13–0.85, p = 0.021, neonatal APO: OR 0.39, 95%CI 0.17–0.90, p = 0.028). Conversely, no statistical difference was observed in the APO ratio based on serological activity in pregnant patients with clinical remission. (overall APO: OR 0.62, 95%CI 0.21–1.79, p = 0.37, maternal APO: OR 1.25, 95%CI 0.32–4.85, p = 0.75, neonatal APO: OR 0.83, 95%CI 0.29–2.39, p = 0.73). A glucocorticoid dose of prednisolone equivalent ≥ 7.5 mg/day at conception correlated with increased APO. (overall APO: OR 3.01, 95%CI 1.23–7.39, p = 0.016, neonatal APO: OR 2.98, 95% CI:1.23–7.22, p = 0.016).

Conclusions

Even with active serology, achieving clinical remission can be a clinical target for reducing APOs in patients who wish to conceive. In addition, if clinically feasible, reducing the glucocorticoid dosage to < 7.5 mg/day before conception could be another predictive factor.
Novel histone post-translational modifications in Alzheimer’s disease: current advances and implications
Authors: Qin Yuanyuan , Yang Ping , He Wanhong , Li Dongze , Zeng Lisha , Li Junle , Zhou Tingting , Peng Juan , Cao Ling , Huang Wei
Published: March 2024

Alzheimer’s disease (AD) has a complex pathogenesis, and multiple studies have indicated that histone post-translational modifications, especially acetylation, play a significant role in it. With the development of mass spectrometry and proteomics, an increasing number of novel HPTMs, including lactoylation, crotonylation,β-hydroxybutyrylation, 2-hydroxyisobutyrylation, succinylation, and malonylation, have been identified. These novel HPTMs closely link substance metabolism to gene regulation, and an increasing number of relevant studies on the relationship between novel HPTMs and AD have become available. This review summarizes the current advances and implications of novel HPTMs in AD, providing insight into the deeper pathogenesis of AD and the development of novel drugs.
Profound postinduction hypotension precipitated by immune checkpoint inhibitors: a case report
Authors: Che Lu , Zhu Afang , Chen Wen , Yu Chunhua
Published: March 2024

Background

With the increasing use of immune checkpoint inhibitors (ICIs) in cancer therapy, perioperative healthcare professionals need to be vigilant about potential immune-related adverse events (irAEs). We report a case of severe postinduction hypotension in a patient undergoing laparotomy due to suspected intraabdominal bleeding from gastric cancer and Krukenberg tumors, caused by unrecognized hypothyroidism precipitated by ICIs.

Case presentation

A 65-year-old Chinese female with a history of gastric adenocarcinoma and Krukenberg tumors, previously treated with nivolumab, presented to the emergency room with abdominal pain and hypotension. Despite ruling out other causes, including hypovolemia and anaphylaxis, her hypotension persisted. The patient was found to have severe hypothyroidism, likely an irAE from the use of nivolumab. Thyroxine replacement therapy resolved the hypotension, and the patient recovered uneventfully after surgery.

Conclusions

This case underscores the importance of considering irAEs, such as hypothyroidism, in patients treated with ICIs. Perioperative healthcare providers must remain vigilant for potential complications and promptly recognize and manage irAEs to optimize patient outcomes.
Treatment options and outcomes for delayed scapular anatomical neck fractures: a case report and review of the literature
Authors: Amouzadeh Omrani Farzad , Khak Mohammad , Tavakoli Darestani Reza , Afzal Sina , Baroutkoub Mojtaba , Aghaalikhani Mahdi , Barati Hasan
Published: March 2024

Introduction

Scapular anatomical neck fractures are among the most infrequent shoulder girdle fractures. Only seven radiologically confirmed cases of scapular anatomical neck fractures have been documented in the literature to date, of which only one case underwent delayed surgery.

Case presentation

A 34-year-old male Persian patient with morbid obesity was diagnosed with a scapula anatomical neck fracture after a motor vehicle collision. The radiographic assessment of the patient indicated an increase in the scapular glenopolar angle (73.9°). Due to concurrent chest and head injuries, surgical intervention was deferred until 6 weeks following the injury. The posterolateral limited Dupont–Evrard approach was used because of the patient’s extremely high body mass index. Two plates were utilized to achieve stable fixation of the glenoid neck fracture. Following a 1 year follow-up period, complete fracture union was successfully attained, resulting in a constant score of 79.

Conclusions

The most accurate radiographic indicators of these fractures are a superior fracture line located laterally to the coracoid process, a small inferior spike, and an elevated glenopolar angle. The only tendon attached to the glenoid is the long head of the triceps, making these fractures unstable; therefore, surgery is required in the majority of instances. The small size of the fractured component makes stabilization more difficult. Overall, anatomical scapular neck fractures are extremely uncommon and distinguished from other scapular fractures by their unique radiological and biomechanical characteristics. This case highlights the challenges encountered when managing scapular fractures in patients with morbid obesity. The delayed surgical intervention and the choice of surgical approach tailored to the patient’s specific anatomical and physiological considerations proved to be effective in achieving a favorable outcome.
Effects of short-term preoperative intranasal dexmedetomidine plus conventional treatment on delirium following cardiac surgery in patients with sleep disorders
Authors: Fang Jun , Yang Jia , Zhai Mingyu , Zhang Qiong , Zhang Min , Xie Yanhu
Published: March 2024

Study objectives

To assess whether preoperative dexmedetomidine (DEX) nasal drips combined with conventional treatment could mitigate the occurrence of postoperative delirium (POD).

Design

A prospective randomised controlled study.

Setting

The cardiac surgery intensive care unit (CSICU) and patient hospitalisation ward at a university hospital.

Participants

A total of 100 patients (aged ≥60 years) undergoing cardiac surgery at a university hospital between 7 January 2022, and 30 November 2022 met the eligibility criteria and were included in the study.

Interventions

Patients with sleep disorders (Pittsburgh Sleep Quality Index ≥8) were divided into two groups: Group A (the placebo group, n=50), receiving a short-term preoperative placebo combined with conventional treatment and Group B (the DEX group, n=50), receiving short-term preoperative DEX combined with conventional treatment.

Measurements and results

The Confusion Assessment Method for the ICU (CAM-ICU) was used for POD assessment in the CSICU, while the CAM was employed to assess delirium in the patient ward. Group B demonstrated a reduced incidence of POD compared to Group A (12% vs. 30%, odds ratio: 0.318, 95% confidence interval: 0.112–0.905, p=0.027).

Conclusion

The combined treatment involving DEX demonstrated a decreased incidence of POD in elderly individuals with sleep disorders undergoing cardiac surgery compared to the placebo combination treatment.

Trial registration

URL: www.chictr.org.cn with registration number ChiCTR 2100043968, registered on 06/03/2021.
Is it time to re-evaluate anti-parasitic use in companion animals?
Authors: Mulcahy Grace
Published: March 2024

Anti-parasitics are very frequently used in companion animals for both prevention and treatment of parasites. When compared with practices related to parasite control in farmed animals, strategic, risk-based use of anti-parasitics in pet dogs and cats instead of precautionary and calendar-based treatment, is not a mainstream approach. Evidence of growing drug resistance in parasites of these hosts and a realisation of the potential adverse environmental consequences of anti-parasitics used in pets provide reasons to re-evaluate the use of anti-parasitics in companion animals. In order to achieve this, consultation and dialogue with industry stakeholders, as well as animal owners, is required.
BİLİM VE SANAT MERKEZİ ÖĞRENCİLERİNDE SOMUT OLMAYAN KÜLTÜREL MİRAS FARKINDALIĞI: BİR ÇOCUK KONGRESİ ÜZERİNE İNCELEME
Authors: BOLAT Halil
Published: March 2024

Araştırmanın amacı üstün zekalı ve yetenekli öğrencilerin SOKÜM ve medya temalı çocuk kongresine yönelik görüşlerinin incelenmesidir. Araştırma, nitel araştırma desenlerinden olgubilim deseni olarak tasarlanmıştır. Çalışma grubunun belirlenmesinde amaçlı örnekleme yöntemleri arasında yer alan ölçüt örnekleme yöntemi kullanılmıştır. Bilim ve sanat merkezlerine devam eden on ortaokul öğrencisi araştırmanın çalışma grubunu oluşturmuştur. Araştırma verileri araştırmacı tarafından hazırlanan yarı yapılandırılmış görüşme formu aracılığıyla elde edilmiştir. Yarı yapılandırılmış görüşme yoluyla toplanan veriler, içerik analizi yöntemi kullanılarak analiz edilmiştir.
Local Ecological Knowledge of the Whitemouth Croaker, Micropologias furneri among the Caiçaras in the Sepetiba Bay, SE Brazil
Authors: Morado Claudio N. , Andrade-Tubino Magda F. de , Pinto Benjamin C. T. , Araújo Francisco G.
Published: March 2024

Local Ecological Knowledge of artisanal fishers (Caiçaras) was employed to investigate various biological aspects of the Whitemouth croaker (Micropogonias furnieri) in the Sepetiba Bay, in the state of Rio de Janeiro. This included migration patterns, reproduction, feeding habits, and interactions such as parasitism. Semi-structured interviews were carried out with 40 fishers in two communities using the “snowball” technique. It was found that the fisher’s information coincides with the academic literature for some aspects of the biology and ecology of the species. Furthermore, the fishers provided descriptions of novel patterns, which contributed to a deeper understanding of the species' natural history. These included observations of reproduction occurring almost throughout the entire year, the influence of east and north winds on the species' entry into the bay, interactions with marine catfish (Ariidae), and notable records of the isopod Cymothoidae as an important parasite of the Whitemouth croaker. This study contributes new insights to the ecological understanding of this fish species, which holds significant socio-environmental importance. It also documents changes in the livelihoods of artisanal Caiçaras communities resulting from the increasing anthropogenic activities in the region. Finally, it highlights the species' significance in terms of its sale and consumption within these communities, owing to its relative abundance in the area, despite the environmental impacts.
Dating Maps with Sir Francis Drake’s Route of Circumnavigation
Authors: Bahill Terry
Published: March 2024

This paper describes the nine sixteenth-century maps, texts, and globes that showed Sir Francis Drake’s route of circumnavigation of the world. It shows the relationships between these nine artifacts and suggests the year of disclosure for each. The oldest of these is the Whitehall map, which was the direct or indirect precursor of the Drake-Mellon map, the French-Drake Van Sype map, the Dutch-Drake map, and the Hondius Broadside map. Most world maps published between 1561 and 1588 have a huge bulge on the coast of Chile. However, eight of the maps discussed in this paper shrank the bulge and moved it to the southern tip of Chile, using updated information from Drake’s voyage.
NEW ADDITIONS OF LICHENS FROM ASSAM, INDIA
Authors: Behera Prashant Kumar , Joseph Siljo , Nayaka Sanjeeva , Singh Chauhan Rajveer
Published: March 2024

An account of 7 lichen species new to lichen biota of Assam is presented. The species are Bactrospora paludicola, Buellia pleiotera, Byssolecania deplanata, Graphis urandrae, Gyalidea fritzei, Mycobilimbia philippina and Staurothele fissa. Among them, B. paludicola and G. fritzei are being reported for the first time from India. The lichen samples were collected from various protected areas of Assam and a detailed systematic account is provided.
Optimal control of susceptible mature pest concerning disease-induced pest-natural enemy system with cost-effectiveness
Authors: Mathur Kunwer Singh , Kumar Bhagwan
Published: March 2024

This article addresses the pressing issue of pest outbreaks in India, which poses significant challenges for farmers and ecologists. A novel system is proposed for effective control that leverages natural enemies. Here, the pests are classified into juveniles and mature individuals, further categorized as susceptible or infected. The study introduces harvesting, incorporating external efforts and natural phenomena, in a pest-epidemic prey–predator system featuring a prey-stage structure. The model reveals three equilibria: trivial, boundary (indicating the absence of natural enemies), and interior equilibria. Notably, the trivial equilibrium is consistently unstable. As demonstrated by stability analysis, the survival or extinction of natural enemies hinges on control variables, including the harvesting rate, disease transmission rate, and natural death rate. Local stability is assessed using the Routh–Hurwitz criterion, while global stability is explored through the Lyapunov method. Furthermore, optimal control theory and Pontryagin’s maximum principle are applied for model optimization, unveiling crucial optimality conditions and determining the optimal harvesting rate for susceptible mature prey. Numerical computations validate theoretical insights, offering valuable guidance for formulating policies that optimize the control of susceptible adult pests within a disease-induced pest-natural enemy system, ensuring sustained cost-effectiveness.
A mathematical study of the adrenocorticotropic hormone as a regulator of human gene expression in adrenal glands
Authors: Manickam A. , Jaison A. Benevatho , Lakshmi D. , Singh Ram , Pravina C. T. Dora
Published: March 2024

In this research, we have introduced compartments for asymptomatic and symptomatic individuals, along with reduced susceptibility, as key factors defining our investigation. The study is carried out in diverse scenarios, considering them as crucial for the essential generation number of the model, set at 3.18(

r

0

>
1

{r}_{0}\gt 1

). The persistent reproduction differential method was used to explore the impact of continuous adrenocorticotropic hormone (ACTH) administration on the global gene expression in primary cultures of both fetal and adult adrenal cells. The study also investigates ACTH’s genetic effects on both adult and fetal human adrenal cells. The conclusion of this study is demonstrated through relevant and correct medical applications.
Sacrificial anode materials to protect marine grade steel structures: a review
Authors: Vaira Vignesh Ramalingam , Sathiya P.
Published: March 2024

Marine structures are constantly exposed to the corrosive effects of seawater, making effective corrosion protection crucial for their longevity and performance. Sacrificial anodes, commonly made of zinc, aluminum, or magnesium alloys, are widely employed to mitigate corrosion by sacrificing themselves to protect the steel structures. However, the selection and implementation of sacrificial anode materials present various challenges that need to be addressed. This paper explores the challenges associated with sacrificial anode materials for steel structures and provides potential solutions. To overcome these challenges, the paper proposes solutions such as using advanced alloy compositions, protective coatings, hybrid anode systems, and improved design considerations. Furthermore, the importance of monitoring techniques to assess the performance and remaining lifespan of sacrificial anodes is emphasized. Several case studies and experimental findings are discussed to illustrate the effectiveness and limitations of sacrificial anode materials based on zinc alloys, aluminum alloys, and magnesium alloys. The paper highlights the need for ongoing research and development efforts to address the evolving demands of corrosion protection in marine environments.