bluuebunny/crossref_metadata_2025 huggingface dataset:
Helicobacter pylori-induced fibroblast-derived Serpin E1 promotes gastric cancer growth and peritoneal dissemination through p38 MAPK/VEGFA-mediated angiogenesis
Authors: Cheng Wei , Liao Yonghui , Xie Yuan , Wang Qinrong , Li Leilei , Chen Yuanjia , Zhao Yan , Zhou Jianjiang
Published: December 2023

Background

Fibroblasts, especially cancer-associated fibroblasts (CAFs), represent the predominant stromal cell population in the tumor microenvironment and have an important function in tumorigenesis by interacting with tumor cells. However, their interaction remains elusive in an inflammatory tumor microenvironment induced by Helicobacter pylori (H. pylori).

Methods

The expression of Serpin family E member 1 (Serpin E1) was measured in fibroblasts with or without H. pylori infection, and primary gastric cancer (GC) cells. Serpin E1 knockdown and overexpression fibroblasts were generated using Serpin E1 siRNA or lentivirus carrying Serpin E1. Co-culture models of fibroblasts and GC cells or human umbilical vein endothelial cells (HUVECs) were established with direct contact or the Transwell system. In vitro functional experiments and in vivo tumorigenesis assay were employed to study the malignant behaviors of GC cells interacting with fibroblasts. ELISA was used for quantifying the levels of Serpin E1 and VEGFA in the culture supernatant. The tube formation capacity of HUVECs was assessed using a tube formation assay. Recombinant human Serpin E1 (recSerpin E1), anti-Serpin E1 antibody, and a MAPK pathway inhibitor were utilized to treat HUVECs for elucidating the underlying molecular mechanisms.

Results

Serpin E1 was predominantly expressed in gastric CAFs. H. pylori infection significantly enhanced the expression and secretion of Serpin E1 by CAFs. Both fibroblast-derived Serpin E1 and recSerpin E1 enhanced the growth, invasion, and migration of GC cells, along with increased VEGFA expression and tube formation in HUVECs. Furthermore, the co-inoculation of GC cells and fibroblasts overexpressing Serpin E1 triggered the expression of Serpin E1 in cancer cells, which facilitated together xenograft tumor growth and peritoneal dissemination of GC cells in nude mice, with an increased expression of Ki67, Serpin E1, CD31 and/or VEGFA. These processes may be mediated by Serpin E1-induced migration and p38 MAPK/VEGFA-mediated angiogenesis of HUVECs.

Conclusion

H. pylori infection induces Serpin E1 expression in fibroblasts, subsequently triggering its expression in GC cells through their interaction. Serpin E1 derived from these cells promotes the migration and p38 MAPK/VEGFA-mediated angiogenesis of HUVECs, thereby facilitating GC growth and peritoneal metastasis. Targeting Serpin E1 signaling is a potential therapy strategy for H. pylori-induced GC.
PRRG4 regulates mitochondrial function and promotes migratory behaviors of breast cancer cells through the Src-STAT3-POLG axis
Authors: Wang Yang , Wang Jieyi , Chen Lan , Chen Zhuo , Wang Tong , Xiong Shuting , Zhou Tong , Wu Guang , He Licai , Cao Jiawei , Liu Min , Li Hongzhi , Gu Haihua
Published: December 2023

Background

Breast cancer is the leading cause of cancer death for women worldwide. Most of the breast cancer death are due to disease recurrence and metastasis. Increasingly accumulating evidence indicates that mitochondria play key roles in cancer progression and metastasis. Our recent study revealed that transmembrane protein PRRG4 promotes the metastasis of breast cancer. However, it is not clear whether PRRG4 can affect the migration and invasion of breast cancer cells through regulating mitochondria function.

Methods

RNA-seq analyses were performed on breast cancer cells expressing control and PRRG4 shRNAs. Quantitative PCR analysis and measurements of mitochondrial ATP content and oxygen consumption were carried out to explore the roles of PRRG4 in regulating mitochondrial function. Luciferase reporter plasmids containing different lengths of promoter fragments were constructed. Luciferase activities in breast cancer cells transiently transfected with these reporter plasmids were analyzed to examine the effects of PRRG4 overexpression on promoter activity. Transwell assays were performed to determine the effects of PRRG4-regulated pathway on migratory behaviors of breast cancer cells.

Results

Analysis of the RNA-seq data revealed that PRRG4 knockdown decreased the transcript levels of all the mitochondrial protein-encoding genes. Subsequently, studies with PRRG4 knockdown and overexpression showed that PRRG4 expression increased mitochondrial DNA (mtDNA) content. Mechanistically, PRRG4 via Src activated STAT3 in breast cancer cells. Activated STAT3 in turn promoted the transcription of mtDNA polymerase POLG through a STAT3 DNA binding site present in the POLG promoter region, and increased mtDNA content as well as mitochondrial ATP production and oxygen consumption. In addition, PRRG4-mediated activation of STAT3 also enhanced filopodia formation, migration, and invasion of breast cancer cells. Moreover, PRRG4 elevated migratory behaviors and mitochondrial function of breast cancer cells through POLG.

Conclusion

Our results indicate that PRRG4 via the Src-STAT3-POLG axis enhances mitochondrial function and promotes migratory behaviors of breast cancer cells.
Prevalence of depression among people living with HIV in rural hospitals in South-Western Nigeria-Association with clinico-demographic factors
Authors: Adedeji Waheed Adeola , Ma Qing , Raji Abiodun Muhammed , Cha Raymond , Rasaki Olaniran Mudasiru , Hutson Alan , Taiwo Babafemi O. , Charurat Man E. , Yusuf Oyindamola B. , Fehintola Fatai Adewale , Gureje Oye , Morse Gene D.
Published: December 2023

Major depression is the most common neuropsychiatric disorder among people living with HIV (PLWH) and is predictive of high morbidity and mortality among them. This study estimated the prevalence and explored factors associated with depression among PLWH in two rural secondary health facilities providing anti-retroviral therapy (ART) services in Southwestern Nigeria between September and December 2020. The Patient Health Questionnaire-9 (PHQ-9) was used to screen and identify PLWH aged 18 years or older with depression. Descriptive statistics, bivariate and multivariate analyses were performed with SPSS version 23. A total of 172 respondents were screened. The prevalence of depression was 16.3% (95% CI 11.1%, 22.7%). Mild, moderate, and moderately severe depression was identified in 17 (9.9%), 8(4.7%) and 3(1.7%) of the participants, respectively. One (0.6%) respondent had suicidal ideation. Of PLWH with any depression, 20/28(71.4%) were within the 40–59 years of age range. None of the participants was on antidepressants. The factor most associated with depression was hypertension, with adjusted odd ratios of 9.8(95% CI 3.5–27.3, p < 0.0001). The study highlights the importance of screening for the severity of depression among PLWH in rural hospitals providing ART services in Africa. PLWH with comorbid hypertension were more likely to suffer from some form of depression.
Constructing public–private partnerships to undermine the public interest: critical discourse analysis of Working Together published by the International Alliance for Responsible Drinking
Authors: Madden Mary , Bartlett Andrew , McCambridge Jim
Published: December 2023

Background

The global burden of alcohol harm has increased and is forecast to grow further without effective policy implementation. Public–private partnerships aiming to address global health, and other societal challenges, are a burgeoning feature of neoliberal governance. Rhetorically distancing themselves from tobacco, the major alcohol companies are committed to tackling ‘harmful drinking’ and have created a distinct type of public relations organization for this purpose. The activities of such organizations are increasingly recognized as an impediment to the implementation of policies to reduce alcohol harm, including in low- and middle-income countries where markets are expanding.

Methods

The approach of critical discourse analysis is used to examine the discursive tactics and strategies used inWorking Together; a ‘toolkit’ published by the key global level alcohol industry public relations organization, the International Alliance for Responsible Drinking (IARD). This study considers how it works discursively to set the terms of, and overcome skepticism about partnerships, to define aims and position various actors by constructing their roles. The construction of prospective partners provides insights into the alcohol industry itself.

Results

The toolkit operates as an ideological resource for forming public–private partnerships across the world based on the accumulated know-how of the major companies through IARD. This allows the largest alcohol companies to exercise leadership of the industry, while remaining off-stage. The toolkit relies on a form of rhetorical work which creates distance from obvious corporate interests and the harms caused to population health and society. This is accomplished by workingagainstevidence-informed population level approaches, and thus avoiding policies that will make any significant difference to overall alcohol harm. Unspecific “complexity” affords opportunity for preferred types of “actions”, and “partnership” provides opportunity to gain credibility by association, further minimizing the likelihood of any material harm being reduced.

Conclusions

The toolkit is designed to not only legitimate the inclusion of alcohol industry actors as initiating ‘partners’, but also assigns them roles as managers of a set of carefully constructed relationships. This vision of public–private partnership reproduces the hegemonic narrative that has successfully blocked policy advances for decades and led to growing alcohol harm globally.
No evidence of genetic causality between diabetes and osteonecrosis: a bidirectional two-sample Mendelian randomization analysis
Authors: Li Wei , Chai Jin-Lian , Li Zhe , Guo Cong-Cong , Wei Ran , Sun Tie-Feng , Liang Xue-Zhen
Published: December 2023

Objective

This study aimed to examine whether diabetes mellitus is causally associated with osteonecrosis.

Method

Using publicly accessible genome-wide association study statistics, a bidirectional two-sample Mendelian randomization analysis was carried out. In order to determine whether diabetes has a causal effect on osteonecrosis and whether osteonecrosis has a causal effect on diabetes, we extracted six date on diabetes in Europeans from IEU OpenGWAS and GWAS Catalogue and osteonecrosis in Europeans from FinnGen. We then evaluated the data using inverse variance weighting, MR-Egger regression, weighted median, weighted mode, and simple mode. The results’ stability and dependability were then evaluated using sensitivity analysis and heterogeneity analysis. Finally, meta-analysis is used to further confirm if there is a relationship between diabetes and osteonecrosis.

Results

When diabetes was used as an exposure factor, MR-Egger regression showed that directional fold product was unlikely to bias the results. Cochran’s Q test showed only minor heterogeneity in a few data sets. Multidirectional tests Egger-intercept, MR-PRESSO and funnel plots for most data did not show multidirectional and asymmetry at the gene level. Most of the IVW results showed no causal relationship between diabetes mellitus and osteonecrosis. The results of meta-analysis of IVW methods further confirmed the absence of a causal relationship. Inverse MR analysis also showed no causal relationship between osteonecrosis and diabetes.

Conclusion

Results of bidirectional MR analysis show no evidence of causal relationship between diabetes and osteonecrosis.
Harnessing immunotherapy for brain metastases: insights into tumor–brain microenvironment interactions and emerging treatment modalities
Authors: Zhou Dairan , Gong Zhenyu , Wu Dejun , Ma Chao , Hou Lijun , Niu Xiaomin , Xu Tao
Published: December 2023

Brain metastases signify a deleterious milestone in the progression of several advanced cancers, predominantly originating from lung, breast and melanoma malignancies, with a median survival timeframe nearing six months. Existing therapeutic regimens yield suboptimal outcomes; however, burgeoning insights into the tumor microenvironment, particularly the immunosuppressive milieu engendered by tumor–brain interplay, posit immunotherapy as a promising avenue for ameliorating brain metastases. In this review, we meticulously delineate the research advancements concerning the microenvironment of brain metastases, striving to elucidate the panorama of their onset and evolution. We encapsulate three emergent immunotherapeutic strategies, namely immune checkpoint inhibition, chimeric antigen receptor (CAR) T cell transplantation and glial cell-targeted immunoenhancement. We underscore the imperative of aligning immunotherapy development with in-depth understanding of the tumor microenvironment and engendering innovative delivery platforms. Moreover, the integration with established or avant-garde physical methodologies and localized applications warrants consideration in the prevailing therapeutic schema.
Characterization of an efficient N-oxygenase from Saccharothrix sp. and its application in the synthesis of azomycin
Authors: Fan Chuanle , Zhou Fang , Huang Wei , Xue Yi , Xu Chao , Zhang Rubing , Xian Mo , Feng Xinjun
Published: December 2023

Background

The nitro group constitutes a significant functional moiety within numerous valuable substances, such as nitroimidazoles, a class of antimicrobial drugs exhibiting broad spectrum activity. Conventional chemical methods for synthesizing nitro compounds suffer from harsh conditions, multiple steps, and environmental issues. Biocatalysis has emerged as a promising alternative to overcome these drawbacks, with certain enzymes capable of catalyzing nitro group formation gradually being discovered in nature. Nevertheless, the practical application is hindered by the restricted diversity and low catalytic activity exhibited by the reported nitrifying enzymes.

Results

A novel N-oxygenase SaRohS harboring higher catalytic capability of transformation 2-aminoimidazole to azomycin was characterized from Saccharothrix sp. Phylogenetic tree analysis revealed that SaRohS belongs to the heme-oxygenase-like diiron oxygenase (HDOs) family. SaRohS exhibited optimal activity at pH 5.5 and 25 ℃, respectively. The enzyme maintained relatively stable activity within the pH range of 4.5 to 6.5 and the temperature range of 20 ℃ to 35 ℃. Following sequence alignment and structural analysis, several promising amino acid residues were meticulously chosen for catalytic performance evaluation. Site-directed mutations showed that threonine 75 was essential for the catalytic activity. The dual mutant enzyme G95A/K115T exhibited the highest catalytic efficiency, which was approximately 5.8-fold higher than that of the wild-type and 22.3-fold higher than that of the reported N-oxygenase KaRohS from Kitasatospora azatica. The underlying catalytic mechanism was investigated through molecular docking and molecular dynamics. Finally, whole-cell biocatalysis was performed and 2-aminoimidazole could be effectively converted into azomycin with a reaction conversion rate of 42% within 14 h.

Conclusions

An efficient N-oxygenase that catalyzes 2-aminoimidazole to azomycin was screened form Saccharothrix sp., its phylogenetics and enzymatic properties were analyzed. Through site-directed mutation, enhancements in catalytic competence were achieved, and the molecular basis underlying the enhanced enzymatic activity of the mutants was revealed via molecular docking and dynamic simulation. Furthermore, the application potential of this enzyme was assessed through whole cell biocatalysis, demonstrating it as a promising alternative method for azomycin production.

Graphical Abstract
Reproducibility of peak moment for isometric and isokinetic knee extension exercise
Authors: Zöger Manfred , Nimmerichter Alfred , Baca Arnold , Wirth Klaus
Published: December 2023

Background

Accurate measurements of muscular performance are important for diagnostics, for example during rehabilitation after traumatic injuries but also in competitive sports. For these purposes, dynamometric devices are widely used and considered the gold standard for muscle strength testing. However, few previous studies have tested the reproducibility of peak moment (PM) at velocities close to the maximum device capability, and in general, reproducibility results cannot be transferred to other devices or test protocols. The purpose of this study was to evaluate the reproducibility of PM for different isometric and isokinetic knee extension exercises using the IsoMed 2000.

Methods

Thirty subjects volunteered in three repeated test sessions, including isometric knee extension (100° and 140° knee angle) and isokinetic knee extension (30°/s and 400°/s). Statistical analysis for comparison of sessions two and three included paired sample t-test, calculation of intraclass correlation coefficient (ICC) and standard error of measurement (SEM). Additionally, Bland Altman statistics and corresponding plots were created.

Results

A significant difference between sessions in PM was found for isometric knee extension in one leg (140° left). Reproducibility was high for all conditions with ICC ranging from 0.964 to 0.988 and SEM in the range of 7.6 to 10.5 Nm. Bland Altman statistics revealed a bias between − 7.3 and 0.7 Nm.

Conclusions

Reproducibility of PM using the IsoMed 2000 was good after an initial familiarization trial with high values of relative reproducibility. Absolute reproducibility can be interpreted as appropriate for most common practical applications.
Cotyledonoid dissecting leiomyoma of the uterus: a case report and review of the literature
Authors: Chahkandi Mahboobeh , Ataei Marzieh , Bina Amir Reza , Mozayani Farnaz , Fanoodi Ali
Published: December 2023

Background

Cotyledonoid dissecting leiomyoma, also named Sternberg tumor, is a rare variant of uterine leiomyoma. The tumor is benign, but the appearance and growth pattern are unusual and alarming. In this article, we report a case of cotyledonoid dissecting leiomyoma in a 55-year-old woman as well as review relevant literature.

Case presentation

We report a case of cotyledonoid dissecting leiomyoma in a 55-year-old Iranian woman who presented with vaginal bleeding 4 months after menopause. Ultrasound showed two heterogeneous hypoechoic masses on the uterine fundus. Total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed for the patient. Macroscopically, a large heterogeneous intramural mass (140 mm × 120 mm × 120 mm) with a grape-like exophytic mass on the fundus was observed. Her health status was good after surgery, and the patient was discharged from the hospital after 2 days. In a 1-year follow-up period, no recurrence or any other related complications were found.

Conclusion

It is important to recognize this rare variant of leiomyoma to prevent aggressive and inappropriate overdiagnosis and overtreatment. It is suggested to try to use frozen sections for better diagnosis and to preserve fertility in young women suffering from this lesion.
Hypoxia enhances human myoblast differentiation: involvement of HIF1α and impact of DUX4, the FSHD causal gene
Authors: Nguyen Thuy-Hang , Paprzycki Lise , Legrand Alexandre , Declèves Anne-Emilie , Heher Philipp , Limpens Maelle , Belayew Alexandra , Banerji Christopher R. S. , Zammit Peter S. , Tassin Alexandra
Published: December 2023

Background

Hypoxia is known to modify skeletal muscle biological functions and muscle regeneration. However, the mechanisms underlying the effects of hypoxia on human myoblast differentiation remain unclear. The hypoxic response pathway is of particular interest in patients with hereditary muscular dystrophies since many present respiratory impairment and muscle regeneration defects. For example, an altered hypoxia response characterizes the muscles of patients with facioscapulohumeral dystrophy (FSHD).

Methods

We examined the impact of hypoxia on the differentiation of human immortalized myoblasts (LHCN-M2) cultured in normoxia (PO2: 21%) or hypoxia (PO2: 1%). Cells were grown in proliferation (myoblasts) or differentiation medium for 2 (myocytes) or 4 days (myotubes). We evaluated proliferation rate by EdU incorporation, used myogenin-positive nuclei as a differentiation marker for myocytes, and determined the fusion index and myosin heavy chain-positive area in myotubes. The contribution of HIF1α was studied by gain (CoCl2) and loss (siRNAs) of function experiments. We further examined hypoxia in LHCN-M2-iDUX4 myoblasts with inducible expression of DUX4, the transcription factor underlying FSHD pathology.

Results

We found that the hypoxic response did not impact myoblast proliferation but activated precocious myogenic differentiation and that HIF1α was critical for this process. Hypoxia also enhanced the late differentiation of human myocytes, but in an HIF1α-independent manner. Interestingly, the impact of hypoxia on muscle cell proliferation was influenced by dexamethasone. In the FSHD pathological context, DUX4 suppressed HIF1α-mediated precocious muscle differentiation.

Conclusion

Hypoxia stimulates myogenic differentiation in healthy myoblasts, with HIF1α-dependent early steps. In FSHD, DUX4-HIF1α interplay indicates a novel mechanism by which DUX4 could interfere with HIF1α function in the myogenic program and therefore with FSHD muscle performance and regeneration.
Angiotensin II treatment is associated with improved oxygenation in ARDS patients with refractory vasodilatory shock
Authors: Leisman Daniel E. , Handisides Damian R. , Chawla Lakhmir S. , Albertson Timothy E. , Busse Laurence W. , Boldt David W. , Deane Adam M. , Gong Michelle N. , Ham Kealy R. , Khanna Ashish K. , Ostermann Marlies , McCurdy Michael T. , Thompson B. Taylor , Tumlin James S. , Adams Christopher D. , Hodges Tony N. , Bellomo Rinaldo
Published: December 2023

Background

The physiological effects of renin-angiotensin system modulation in acute respiratory distress syndrome (ARDS) remain controversial and have not been investigated in randomized trials. We sought to determine whether angiotensin-II treatment is associated with improved oxygenation in shock-associated ARDS.

Methods

Post-hoc subgroup analysis of the Angiotensin Therapy for High Output Shock (ATHOS-3) trial. We studied patients who met modified Berlin ARDS criteria at enrollment. The primary outcome was PaO2/FiO2-ratio (P:F) at 48-h adjusted for baseline P:F. Secondary outcomes included oxygenation index, ventilatory ratio, PEEP, minute-ventilation, hemodynamic measures, patients alive and ventilator-free by day-7, and mortality.

Results

Of 81 ARDS patients, 34 (42%) and 47 (58%) were randomized to angiotensin-II or placebo, respectively. In angiotensin-II patients, mean P:F increased from 155 mmHg (SD: 69) at baseline to 265 mmHg (SD: 160) at hour-48 compared with no change with placebo (148 mmHg (SD: 63) at baseline versus 164 mmHg (SD: 74) at hour-48)(baseline-adjusted difference: + 98.4 mmHg [95%CI 35.2–161.5], p = 0.0028). Similarly, oxygenation index decreased by − 6.0 cmH2O/mmHg at hour-48 with angiotensin-II versus − 0.4 cmH2O/mmHg with placebo (baseline-adjusted difference: -4.8 cmH2O/mmHg, [95%CI − 8.6 to − 1.1], p = 0.0273). There was no difference in PEEP, minute ventilation, or ventilatory ratio. Twenty-two (64.7%) angiotensin-II patients had sustained hemodynamic response to treatment at hour-3 versus 17 (36.2%) placebo patients (absolute risk-difference: 28.5% [95%CI 6.5–47.0%], p = 0.0120). At day-7, 7/34 (20.6%) angiotensin-II patients were alive and ventilator-free versus 5/47(10.6%) placebo patients. Day-28 mortality was 55.9% in the angiotensin-II group versus 68.1% in the placebo group.

Conclusions

In post-hoc analysis of the ATHOS-3 trial, angiotensin-II was associated with improved oxygenation versus placebo among patients with ARDS and catecholamine-refractory vasodilatory shock. These findings provide a physiologic rationale for trials of angiotensin-II as treatment for ARDS with vasodilatory shock.

Trial Registration: ClinicalTrials.Gov Identifier: NCT02338843 (Registered January 14th 2015).
International relations challenges and sustainable development in developing countries after 2022: conceptualization of the risk assessment model
Authors: Stevanović Miroslav , Pavlićević Predrag , Vujinović Nikola , Radovanović Mirjana
Published: December 2023

Background

UN defined Transforming our world: the 2030 Agenda for Sustainable Development promotes international relations as a platform of cooperation between all stakeholders to achieve peace, stability, and prosperity but faces significant challenges in the post-2022 period. In light of the COVID-19 pandemic and the Ukraine crisis, the prospects for sustainable development as a component of international relations are one of the challenges. The main objective of this paper is the conceptualization of a model for sustainable development risk analysis, intended for developing countries with underdeveloped or nonexistent monitoring systems.

Methods

Theory synthesis, adaption, and model development were used in the conceptual method due to empirical research limitations. Analysis, induction, and modeling were utilized to evaluate qualitative and quantitative sustainable development risk assessment approaches and anticipate their advantages and disadvantages.

Results

The theoretical part of the research points to the need to consider the risks to implementing sustainable development (primarily future energy development and climate change) that arise from changes in international security. The novel result of the paper is the proposal of the concept Model for sustainable development implementation risk assessment in developing countries, derived from the following inputs: (a) an overview of the development of international relations and attitudes towards sustainable development; (b) a proposal of a generic model for risk assessment; (c) a prediction of the sustainable development future from the perspective of international relations and defined risks for its implementation. A set of indicators is proposed by dimensions: social, economic–political, and energy-environment.

Conclusions

The future of sustainable development can be considered at a certain degree of risk in light of the global crisis after 2022. Changes in geopolitical constellations, armed conflicts, population growth, climate change, and the reallocation of financial resources are the factors that will largely determine the commitment of individual countries to implementing sustainable development. Therefore, sustainable development risk assessment must be revisited, improved, and closely monitored. The development of models based on the specificities of each country is highly recommended. Methodological notes are presented.
Reduction of ammonia gas by microbial agent treatment in Chinese cabbage cultivation
Authors: Park Jong-Hwan , Lee Su-Lim , Lee Jae-Hoon , Rho Jun-Suk , Lee Jeong-Min , Kim Seong-Heon , Kang Se-Won , Seo Dong-Cheol
Published: December 2023

This study aimed to select the optimal microbial agents for ammonia gas reduction in Chinese cabbage cultivation and evaluate their ammonia reduction efficiency. By selecting the optimum microorganism to reduce ammonia emissions, the ammonia emission reduction efficiencies of the nitrification microorganisms, Alcaligenes faecalis subsp. faecalis and Brevibacillus sp. were 21 and 31%, respectively, which were superior to those of other microorganisms. The best ammonia emission reduction efficiency of the acid-producing microorganisms was 55%. The optimum mixing ratio of microbial agent for removing ammonia gas emitted from NPK-containing soil was: acid-producing microorganism:Alcaligenes faecalis subsp. faecalis:Brevibaillus sp. = 0.70:0.15:0.15. The optimum treatment amount was 500 L/ha, and the optimum number of microbial agents was basal fertilization (also known as pre-planting fertilization) once and additional fertilization three times, for a total of four times. The reduction efficiency of ammonia emissions from NPK-containing soil under optimum conditions in cabbage cultivation was 27% lower than that of the control (only NPK-containing soil). Therefore, the microbial agent developed in this study can be utilized to effectively reduce the emission of ammonia, a secondary fine particle precursor, while maintaining crop yield in agricultural fields.
Improved oxygenation in prone positioning of mechanically ventilated patients with COVID-19 acute respiratory distress syndrome is associated with decreased pulmonary shunt fraction: a prospective multicenter study
Authors: Harbut Piotr , Campoccia Jalde Francesca , Dahlberg Martin , Forsgren Anders , Andersson Elisabeth , Lundholm Andreas , Janc Jaroslaw , Lesnik Patrycja , Suchanski Michal , Zatorski Pawel , Trzebicki Janusz , Skalec Tomasz , Günther Mattias
Published: December 2023

Background

Prone position is used in acute respiratory distress syndrome and in coronavirus disease 2019 (Covid-19) acute respiratory distress syndrome (ARDS). However, physiological mechanisms remain unclear. The aim of this study was to determine whether improved oxygenation was related to pulmonary shunt fraction (Q’s/Q’t), alveolar dead space (Vd/Vtalv) and ventilation/perfusion mismatch (V’A/Q’).

Methods

This was an international, prospective, observational, multicenter, cohort study, including six intensive care units in Sweden and Poland and 71 mechanically ventilated adult patients.

Results

Prone position increased PaO2:FiO2 after 30 min, by 78% (83–148 mm Hg). The effect persisted 120 min after return to supine (p < 0.001). The oxygenation index decreased 30 min after prone positioning by 43% (21–12 units). Q’s/Q’t decreased already after 30 min in the prone position by 17% (0.41–0.34). The effect persisted 120 min after return to supine (p < 0.005). Q’s/Q’t and PaO2:FiO2 were correlated both in prone (Beta -137) (p < 0.001) and in the supine position (Beta -270) (p < 0.001). V’A/Q’ was unaffected and did not correlate to PaO2:FiO2 (p = 0.8). Vd/Vtalv increased at 120 min by 11% (0.55–0.61) (p < 0.05) and did not correlate to PaO2:FiO2 (p = 0.3). The ventilatory ratio increased after 30 min in the prone position by 58% (1.9–3.0) (p < 0.001). PaO2:FiO2 at baseline predicted PaO2:FiO2 at 30 min after proning (Beta 1.3) (p < 0.001).

Conclusions

Improved oxygenation by prone positioning in COVID-19 ARDS patients was primarily associated with a decrease in pulmonary shunt fraction. Dead space remained high and the global V’A/Q’ measure could not explain the differences in gas exchange.
Association between clonal hematopoiesis-related gene mutations and unfavorable functional outcome in patients with large-artery atherosclerotic stroke
Authors: Qiu Xin , Weng Jiaxu , Jiang Yingyu , Cui Lingyun , Gu Hongqiu , Jiang Yong , Dai Yalun , Li Hao , Wang Yongjun , Li Zixiao
Published: December 2023

Background

Clonal hematopoiesis of indeterminate potential (CHIP) is a phenomenon that characterizes individuals with somatic mutations that are related to hematologic malignancy but without hematologic abnormalities. Presence of CHIP is associated with the atherosclerotic cardiovascular disease through the activation of the interleukin 6 (IL-6) pathway; however, its role on unfavorable functional outcomes in different etiologies of ischemic stroke remains unclear. We aimed to investigate the association between CHIP-related gene mutations and unfavorable functional outcomes of ischemic stroke with different etiologies.

Methods

We prospectively studied a cohort of 3396 stroke patients with identified etiologies, and identified CHIP and the presence of the IL6R variant (IL6R p.Asp358Ala) by whole-genome sequencing. The IL6R p.Asp358Ala coding mutation was used as a genetic inhibition for IL-6 signaling. The primary outcome was unfavorable functional outcome [(Modified Rankin Scale), mRS 2–6] at 3 months.

Results

Of the 3396 patients, 110 (3.2%) were CHIP carriers and the median age was 62 years (IQR, 54.0–69.0). The CHIP increased the risk of unfavorable functional outcome among patients with hyper-inflammation status of high-sensitivity C-reactive protein (hsCRP) > median levels in patients with large-artery atherosclerosis (LAA) (OR 2.45, 95% CI 1.00–5.98, p = 0.049, pinteraction = 0.01). Presence of IL6R variant (IL6R p.Asp358Ala) could attenuate the risk of unfavorable functional outcome only in patients with CHIP (OR 0.30, 95%CI 0.12–0.76, p = 0.01, pinteraction = 0.02), and especially in LAA patients with CHIP (OR 0.1, 95%CI 0.02–0.42, p = 0.002; pinteraction = 0.001).

Conclusion

CHIP is associated with unfavorable functional outcomes in patients with LAA stroke and hyper-inflammation. Genetic IL-6 signaling inhibition might attenuate the risk of unfavorable functional outcomes in CHIP carriers, especially in LAA stroke patients.
Evaluating culture and arts from an economic point of view: calculation of the cultural GDP of Kyoto Prefecture in 2015
Authors: Heming Zhang , Taku Ishiro
Published: December 2023

This paper aims to evaluate the culture and arts of Kyoto Prefecture through the calculation of its cultural GDP in 2015. The method for calculating the cultural GDP in Japan is mainly based on the criterion of the UNESCO Culture Satellite Account (CSA). Results reveal that the ratio of the cultural GDP to the total GDP in Kyoto Prefecture (about 2.0%) is slightly higher than that of the whole country in Japan (about 1.8%) and each domain shows different characteristics from the national situation. Considering the growth strategies of cultural industries formulated by Japanese government, Kyoto Prefecture should focus on developing its competitive tertiary industry and vigorously promote its cultural industries as well as activate the development of the traditional culture.
A systematic review assessing incorporation of prophylactic splenic artery embolisation (pSAE) into trauma guidelines for the management of high-grade splenic injury
Authors: Clements Warren , Fitzgerald Mark , Chennapragada S. Murthy , Mathew Joseph , Groombridge Christopher , Ban Ee Jun , Lukies Matthew W.
Published: December 2023

Background

Splenic artery embolisation (SAE) has become a vital strategy in the modern landscape of multidisciplinary trauma care, improving splenic salvage rates in patients with high-grade injury. However, due to a lack of prospective data there remains contention amongst stakeholders as to whether SAE should be performed at the time of presentation (prophylactic or pSAE), or whether patients should be observed, and SAE only used only if a patient re-bleeds. This systematic review aimed to assess published practice management guidelines which recommend pSAE, stratified according to their quality.

Methods

The study was registered and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Medline, PubMed, Cochrane, Embase, and Google Scholar were searched by the study authors. Identified guidelines were graded according to the Appraisal of Guidelines Research and Evaluation II (AGREE-II) instrument.

Results

Database and internet searches identified 1006 results. After applying exclusion criteria, 28 guidelines were included. The use of pSAE was recommended in 15 guidelines (54%). This included 6 out of 9 guidelines that were high quality (66.7%), 4 out of 9 guidelines that were moderate quality (44.4%), and 3 out of 10 (30%) guidelines that were low quality, p = 0.275.

Conclusions

This systematic review showed that recommendation of pSAE is more common in guidelines which are of high quality. However, there is vast heterogeneity of recommended practice guidelines, likely based on individual trauma systems rather than the available evidence. This reflects biases with interpretation of data and lack of multidisciplinary system inputs, including from interventional radiologists.
Association between miR-138-5p, miR-132-3p, SIRT1, STAT3, and CD36 and atherogenic indices in blood mononuclear cells from patients with atherosclerosis
Authors: Ehsani Samira , Mard‑Soltani Maysam , Ahmadpour Fatemeh , Shahsavari Gholamreza
Published: December 2023

Backgrounds

Developed countries have a high mortality rate from atherosclerosis and are frequently linked to inflammation and other blood lipid disorders. MicroRNA expression can affect atherosclerotic plaque formation, lipid metabolism, inflammation, and other related processes. The search aimed to determine whether microRNA-138-5p or microRNA-132-3p expression levels are related to patient atherogenic genes.

Methods

Angiographic diagnostic method was used to select 45 healthy samples and 45 atherosclerosis patients, along with the laboratory and demographic information. After isolating peripheral blood mononuclear cells (PBMCs) from blood, the levels of miR-138 and miR-132 and the relative expression of Sirtuin 1 (SIRT1), signal transducer and activator of transcription-3 (STAT3), and CD36 genes measured using real-time PCR.

Results

miR-138 was upregulated compared to the control group in the atherosclerosis patient group (P < 0.05). In contrast, SIRT1 was downregulated in patients (P < 0.05). Our results also showed that the expression levels of miR-138 can use as a biomarker for atherosclerosis detection (P < 0.05). In addition, the expression of miR-138 with SIRT1 had a significant negative correlation (P < 0.05), and miR-132 was directly correlated with STAT3 (P < 0.01). Interestingly, STAT3 was negatively correlated with SIRT1 (P < 0.05) and positively with CD36 (P < 0.01).

Conclusion

Since atherosclerosis has no specific clinical symptoms and early diagnosis is vital, the use of miR-138 diagnostic biomarkers can play an essential role in early diagnosis. Furthermore, this study highlights the overlap of SIRT1-STAT3-CD36 signaling pathways with miR-132 and miR-138 in atherosclerosis.
Nanotoxicological profiles of clinically approved nanoplatforms
Authors: Nkanga Christian Isalomboto
Published: December 2023

Background

Nanoparticles (NPs) engineering offers great opportunities to produce versatile materials for multiple applications in medicine, including drug delivery and bioimaging. Successful development of nanomedicines up to the clinical level is evidence that nanotechnology has made gigantic strides in addressing health problems.

Area covered

This review briefly discusses the toxicological data from selected clinically relevant nanoplatform technologies (i.e. liposomes, poly(lactide-co-glycolide) and iron oxide NPs); comparisons between such nano-systems provide insights into existing challenges in nanotoxicity assessment. The factors that can affect nanoparticles toxicity have been discussed as well. Albeit most studies reported no major toxicological effects, the analysis of reported data pinpoints the lack of organ-function studies as well as the difficulty in comparing nanotoxicity findings from different protocols due to the discrepancies in experimental conditions.

Conclusion

The previously developed nanomedicines are likely a result of constant efforts dedicated to improving the quality attributes of individual products on case-by-case basis, given the luck of design rules for optimal nanoproducts. Thus, further systematic investigations are required to streamline the general design principles in nanoproducts development and boost the translation of NPs from bench to bedside.
Impaired Thyroid Hormone Sensitivity Increases Risk of Cardiovascular Events in Patients Undergoing Coronary Angiography
Authors: Qin Zhizhen , Muhanhali Dilidaer , Ling Yan
Published: December 2023

Context

Previous studies found inconsistent results on the relationship between thyroid function and cardiovascular risks.

Objective

This study aimed to investigate the association of thyroid hormone sensitivity with the risk of major adverse cardiovascular events (MACE) and cardiovascular death in a euthyroid population undergoing coronary angiography.

Methods

This prospective cohort study enrolled 1470 euthyroid participants who underwent coronary angiography between March and November of 2013. The participants were followed up from July to November in 2022. Thyrotroph thyroxine resistance index (TT4RI), TSH index (TSHI), and feedback quantile-based index (TFQI) were calculated to evaluate the sensitivity to thyroid hormone. Kaplan–Meier curve and multivariable Cox proportional hazard model were performed to analyze the association between thyroid hormone sensitivity and risk of MACE and cardiovascular death.

Results

Among 1089 participants who completed the follow-up, 342 cases of MACE and 77 cardiovascular deaths were identified during a medium follow-up duration of 111 months. In the multivariable Cox proportional hazard model, the higher levels of TFQI (hazard ratio [HR] = 1.41; 95% CI, 1.08-1.84; P for trend = .01), TT4RI (HR = 1.40; 95% CI, 1.06-1.84; P for trend = .02) and TSHI (HR = 1.61; 95% CI, 1.22-2.13; P for trend = .001) were associated with increased risk of MACE. The higher levels of TFQI (HR = 2.21; 95% CI, 1.17-4.17; P for trend = .02) and TSHI (HR = 2.05; 95% CI; 1.08-3.91; P for trend = .03) were also associated with increased risk of cardiovascular death.

Conclusion

Impaired sensitivity to thyroid hormone is associated with higher risks of MACE and cardiovascular death in a euthyroid population undergoing coronary angiography.
Evaluation of Microvascular Complications in Kidney Recipients With Posttransplant Diabetes Mellitus
Authors: Çelik Kavaklılar Başak , Aybı Özdemir Özge , Yıldırım Tolga , Dikmetaş Özlem , Toprak Hilal , Hekimsoy Vedat , İşler Alperen Onur , Yılmaz Rahmi , Kadayıfçılar Sibel , Erdem Yunus , Erbas Tomris , Ünlütürk Uğur
Published: December 2023

Context

The paucity of data on microvascular complications in patients with posttransplant diabetes (PTDM) is an obstacle to developing follow-up algorithms.

Objective

To evaluate diabetic microvascular complications in patients with long-standing PTDM.

Methods

In patients with ≥5-year history of PTDM and age-matched renal transplant recipients without PTDM (NDM), diabetic peripheral neuropathy was evaluated using the Michigan Neuropathy Screening Instrument, the CASE IV device, and in vivo corneal confocal microscopy (CCM). Cardiac autonomic neuropathy tests were performed using heart rate variability. Nephropathy screening was assessed using spot urine albumin/creatinine ratio and eGFR calculation. Diabetic retinopathy was evaluated by fundus examination and photography, and optical coherence tomography.

Results

This study included 41 patients with PTDM and 45 NDM patients. The median follow-up was 107.5 months in the PTDM group. Peripheral neuropathy was significantly higher in the PTDM group than in the NDM group (P = .02). In the PTDM patients with peripheral neuropathy, corneal nerve fiber density examined by CCM was significantly lower than in PTDM patients without neuropathy (P = .001). Parasympathetic involvement was observed in 58.5% of the PTDM group and 22% of the NDM group (P = .001). Sympathetic involvement was present in 65.9% of the PTDM group and 29.3% of the NDM group (P = .001). Retinopathy was observed in 19.5% of patients in the PTDM group and in none of the NDM patients (P < .001). Renal functions were similar between the study groups.

Conclusion

Cardiac autonomic neuropathy and diabetic retinopathy can affect patients with PTDM at a high rate. Diabetic retinopathy is a threat to the vision of PTDM patients. Diabetic peripheral neuropathy can be detected early in PTDM patients by CCM.
Contemporary Clinical Perspectives on Targeting Remission of Type 2 Diabetes
Authors: Retnakaran Ravi , Kashyap Sangeeta R , Gerstein Hertzel C , Aroda Vanita R
Published: December 2023

It has long been known that some patients with type 2 diabetes (T2DM) can experience sustained metabolic improvement to near-normal levels of glycemia either spontaneously or after medical intervention. Now recognized as remission of diabetes, this intriguing state is currently more feasible than ever before due to profound advances in metabolic surgery, pharmacologic therapy, and regimens of lifestyle modification. This enhanced capacity to induce remission has revealed new pathophysiologic insights, including the presence of a reversible component of the pancreatic beta-cell dysfunction that otherwise drives the chronic progressive nature of T2DM. In doing so, it has changed the therapeutic landscape by offering new potential management objectives and considerations for patients and providers. However, the excitement around these developments must also be tempered by the sobering realities of our current understanding of remission, including the recognition that this condition may not be permanent (resulting in glycemic relapse over time) and that beta-cell function may not be normalized in the setting of remission. These limitations highlight both the many gaps in our current understanding of remission and the caution with which clinical discussions must be handled for clear patient-directed communication of the pros and cons of targeting this outcome in practice. In this mini-review, we consider this rapidly growing literature, including its implications and its limitations, and thereby seek to provide objective balanced perspectives on targeting remission of T2DM in current clinical care.
Anterior Pituitary Transcriptomics Following a High-Fat Diet: Impact of Oxidative Stress on Cell Metabolism
Authors: Miles Tiffany K , Odle Angela K , Byrum Stephanie D , Lagasse Alex , Haney Anessa , Ortega Victoria G , Bolen Cole R , Banik Jewel , Reddick Milla M , Herdman Ashley , MacNicol Melanie C , MacNicol Angus M , Childs Gwen V
Published: December 2023

Anterior pituitary cell function requires a high level of protein synthesis and secretion which depend heavily on mitochondrial adenosine triphosphate production and functional endoplasmic reticula. Obesity adds stress to tissues, requiring them to adapt to inflammation and oxidative stress, and adding to their allostatic load. We hypothesized that pituitary function is vulnerable to the stress of obesity. Here, we utilized a 10- to 15-week high-fat diet (HFD, 60%) in a thermoneutral environment to promote obesity, testing both male and female FVB.129P mice. We quantified serum hormones and cytokines, characterized the metabolic phenotype, and defined changes in the pituitary transcriptome using single-cell RNA-sequencing analysis. Weight gain was significant by 3 weeks in HFD mice, and by 10 weeks all HFD groups had gained 20 g. HFD females (15 weeks) had increased energy expenditure and decreased activity. All HFD groups showed increases in serum leptin and decreases in adiponectin. HFD caused increased inflammatory markers: interleukin-6, resistin, monocyte chemoattractant protein-1, and tumor necrosis factorα. HFD males and females also had increased insulin and increased TSH, and HFD females had decreased serum prolactin and growth hormone pulse amplitude. Pituitary single-cell transcriptomics revealed modest or no changes in pituitary cell gene expression from HFD males after 10 or 15 weeks or from HFD females after 10 weeks. However, HFD females (15 weeks) showed significant numbers of differentially expressed genes in lactotropes and pituitary stem cells. Collectively, these studies reveal that pituitary cells from males appear to be more resilient to the oxidative stress of obesity than females and identify the most vulnerable pituitary cell populations in females.
Notes of a Course of Practical Histology for Medical Students
Authors: Rutherford W. M.
Published: December 2023

At the present time there is much discussion regarding the manner in which Practical Physiology should be taught to medical students. Perceiving the difficulties which physiological teachers have to encounter in carrying out the new regulations of the College of Surgeons, the Editor of this Journal has asked me to give a résumé of my course of Practical Histology. I do not regard my course as perfect, nevertheless I have found it work successfully through several years, and, after having ascertained the modes of tuition adopted elsewhere in this country and in Germany, I have come to the conclusion that on no other system does the student accomplish so much in so short a time.