bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex differences between serum uric acid levels and cardiovascular outcomes in patients with coronary artery disease after stent implantation
Authors: Yuan Song Lin , Kim Moo Hyun , Lee Kwang Min , Jin Xuan , Song Zhao Yan , Park Jong-Sung , Cho Young-Rak , Lim Kyunghee , Yun Sung-Cheol
Published: February 2023

Background

The relationship between elevated serum uric acid (SUA) levels and cardiovascular outcomes after stent implantation remains uncertain. This study sought to evaluate the impact of SUA on 12-month cardiovascular outcomes after stent implantation.

Methods

We performed a retrospective study of patients who successfully underwent stent implantation and enrolled 3,222 patients with coronary artery disease (CAD) from a single center. SUA levels were measured before stent implantation. The patients were divided into six groups (<4, 4–4.9, 5–5.9, 6–6.9, 7–7.9 and ≥ 8 mg/dL) at SUA intervals of 1.0 mg/dL. The incidence of cardiovascular outcomes in the six groups was monitored for 1 year after stent implantation and the hazard ratios were estimated. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for cardiovascular outcomes were estimated using a Cox proportional hazard regression analysis. The primary endpoint was all-cause death. The secondary endpoint was a composite of all-cause death, myocardial infarction, target vessel revascularization, stent thrombosis and stroke. The follow-up duration was 12 months.

Results

Over the 12-month follow-up period, there were 101 all-cause deaths and 218 MACCE. After adjustment for several parameters, the group with SUA levels of more than or equal to 8 mg/dL had significantly higher hazard ratios in the incidence of all-cause death or MACCE. The group with <4.0 mg/dL had significantly higher hazard ratios in all-cause death only in male patients. In contrast, there were no significant differences observed for cardiovascular outcomes in female patients.

Conclusions

Our study identified a U-shaped association between SUA levels and cardiovascular outcomes during 12-month follow-up for males, but not for females. Further studies are warranted to clarify the sex differences between SUA levels and clinical outcomes.
Murine model of elastase-induced proximal thoracic aortic aneurysm through a midline incision in the anterior neck
Authors: Deng Jianqing , Li Dandan , Zhang Xuelin , Lu Weihang , Rong Dan , Wang Xinhao , Sun Guoyi , Jia Senhao , Zhang Hongpeng , Jia Xin , Guo Wei
Published: February 2023

Objective

This study was performed to develop a murine model of elastase-induced proximal thoracic aortic aneurysms (PTAAs).

Methods

The ascending thoracic aorta and aortic arch of adult C57BL/6J male mice were exposed through a midline incision in the anterior neck, followed by peri-adventitial elastase or saline application. The maximal ascending thoracic aorta diameter was measured with high-resolution micro-ultrasound. Twenty-eight days after the operation, the aortas were harvested and analyzed by histopathological examination and qualitative polymerase chain reaction to determine the basic characteristics of the aneurysmal lesions.

Results

Fourteen days after the operation, the dilation rate (mean ± standard error) in the 10-min elastase application group (n = 10, 71.44 ± 10.45%) or 5-min application group (n = 9, 42.67 ± 3.72%) were significantly higher than that in the saline application group (n = 9, 7.37 ± 0.94%, P < 0.001 for both). Histopathological examination revealed aortic wall thickening, degradation of elastin fibers, loss of smooth muscle cells, more vasa vasorum, enhanced extracellular matrix degradation, augmented collagen synthesis, upregulated apoptosis and proliferation capacity of smooth muscle cells, and increased macrophages and CD4+ T cells infiltration in the PTAA lesions. Qualitative analyses indicated higher expression of the proinflammatory markers, matrix metalloproteinase-2 and -9 as well as Collagen III, Collagen I in the PTAAs than in the controls.

Conclusion

We established a novel in vivo mouse model of PTAAs through a midline incision in the anterior neck by peri-adventitial application of elastase. This model may facilitate research into the pathogenesis of PTAA formation and the treatment strategy for this devastating disease.
Cardiac magnetic resonance outperforms echocardiography to predict subsequent implantable cardioverter defibrillator therapies in ST-segment elevation myocardial infarction patients
Authors: Marcos-Garcés Víctor , Perez Nerea , Gavara Jose , Lopez-Lereu Maria P. , Monmeneu Jose V. , Rios-Navarro Cesar , de Dios Elena , Merenciano-González Hector , Gabaldon-Pérez Ana , Ferrero-De-Loma-Osorio Ángel , Martínez-Brotons Ángel , Bondanza Lourdes , Sánchez-Gómez Juan Miguel , Albiach Cristina , Nunez Julio , Bayés-Genís Antoni , Chorro Francisco J. , Ruiz-Granell Ricardo , Bodi Vicente
Published: February 2023

Background

Implantable cardioverter defibrillators (ICD) are effective as a primary prevention measure of ventricular tachyarrhythmias in patients with ST-segment elevation myocardial infarction (STEMI) and depressed left ventricular ejection fraction (LVEF). The implications of using cardiac magnetic resonance (CMR) instead of echocardiography (Echo) to assess LVEF prior to the indication of ICD in this setting are unknown.

Materials and methods

We evaluated 52 STEMI patients (56.6 ± 11 years, 88.5% male) treated with ICD in primary prevention who underwent echocardiography and CMR prior to ICD implantation. ICD implantation was indicated based on the presence of heart failure and depressed LVEF (≤ 35%) by echocardiography, CMR, or both. Prediction of ICD therapies (ICD-T) during follow-up by echocardiography and CMR before ICD implantation was assessed.

Results

Compared to echocardiography, LVEF was lower by cardiac CMR (30.2 ± 9% vs. 37.4 ± 7.6%, p < 0.001). LVEF ≤ 35% was detected in 24 patients (46.2%) by Echo and in 42 (80.7%) by CMR. During a mean follow-up of 6.1 ± 4.2 years, 10 patients received appropriate ICD-T (3.16 ICD-T per 100 person-years): 5 direct shocks to treat very fast ventricular tachycardia or ventricular fibrillation, 3 effective antitachycardia pacing (ATP) for treatment of ventricular tachycardia, and 2 ineffective ATP followed by shock to treat ventricular tachycardia. Echo-LVEF ≤ 35% correctly predicted ICD-T in 4/10 (40%) patients and CMR-LVEF ≤ 35% in 10/10 (100%) patients. CMR-LVEF improved on Echo-LVEF for predicting ICD-T (area under the curve: 0.76 vs. 0.48, p = 0.04).

Conclusion

In STEMI patients treated with ICD, assessment of LVEF by CMR outperforms Echo-LVEF to predict the subsequent use of appropriate ICD therapies.
3-D azimuthal anisotropy structure reveals different deformation modes of the crust and upper mantle in the southeastern Tibetan Plateau
Authors: Zhang Zhiqi , Feng Jikun , Yao Huajian
Published: February 2023

The tectonic evolution and deformation process of the southeastern Tibetan Plateau has been one of the focuses of the geoscience community in recent decades. However, the crustal and mantle deformation mechanism in the southeastern Tibetan Plateau is still under debate. Seismic anisotropy inferred from surface wave tomography could provide critical insights into the deformation mechanism of the Earth’s tectonosphere. Here, we constructed a 3-D azimuthal anisotropy velocity model with Rayleigh wave phase velocity dispersion data from 132 permanent stations to analyze the deformation modes in the southeastern Tibetan Plateau. In the upper crust, the azimuthal anisotropy near the main strike-slip faults exhibits strong magnitude with fast axis subparallel to the fault strike, which is consistent with the rigid block extrusion pattern. In the mid-lower crust, two low-velocity anomalies appeared beneath the Sonpan-Ganzi Terrane and Xiaojiang Fault zone with strong azimuthal anisotropy, which may indicate ductile deformation of the weak mid-lower crust. However, the two low-velocity anomalies are separated by a high-velocity barrier with weak azimuthal anisotropy in the inner zone of the Emeishan large igneous province. In the upper mantle, the anisotropy pattern is relatively simple in the rigid Yangtze Craton and mainly represents fossil anisotropy. In the southern part, the lithosphere thinned beneath the Indochina and Cathaysia Blocks, and the anisotropy is plausibly caused by the upwelling and lateral flows of upwelling hot asthenospheric materials.
Dynamics of debris flow-induced impacting onto rigid barrier with material source erosion-entrainment process
Authors: Li Bailong , Fang Youliang , Li Yanying , Zhu Chun
Published: February 2023

The dynamics of debris flow impact considering the material source erosion-entrainment process is analyzed using a coupled SPH-DEM-FEM method. A complex coupled dynamic model of a debris flow, the erodible material source, and a rigid barrier is established in this paper. The applicability of the coupled SPH-DEM-FEM method for calculating the impact force of debris flow on the rigid barrier is verified by comparing the model with the laboratory test. The strain softening model is used to simulate the process from solid state to transition state and finally to liquid state of erodible material source. The impact force caused by debris flow considering the source erosion-entrainment process and the dynamic response of a rigid barrier is also analyzed. The results show that the volume of debris fluid, impact force, and dynamic response of a rigid barrier considering source erosion–entrainment are significantly greater than those of the original model. According to the calculation results, the existing formula for the impact force of a debris flow is then modified. The coupled numerical analysis method and the calculated results help to clarify the influence of erosion-entrainment, modify the calculation of the impact force of debris flow, and optimize the design of the rigid barrier.
Promoting creative autonomy support in school music education: An intervention study targeting interaction
Authors: Hendriks Linda H. , Steenbeek Henderien W. , Bisschop Boele Evert H. , van Geert Paul L. C.
Published: February 2023

Introduction

The notion of autonomy in Self-Determination Theory is at the core of intrinsically motivated learning, and fulfilment of the need for autonomy is essential for thriving at school. Therefore teacher-provided autonomy support has grown into a key concern in educational research. In the present study into primary school music education, the notion of creative autonomy support is introduced. Research into autonomy support is typically focused on verbal interaction. However, from an enactive perspective, teachers’ gesturing, bodily movement, facial expression, and musical action form an integral part of the socially situated interaction in music lessons, inherently involving autonomy support. In the present study, a distinction is made between creative verbal autonomy support and creative musical and non-verbal autonomy support.

Methods

Applying a process-based time-serial methodology, rooted in a Complex Dynamic Systems and Enactive perspective, the effects of an intervention with Video Feedback Coaching for teachers were investigated. Video data of 105 music lessons of 18 teachers (intervention and control condition) from six primary schools was gathered, to examine teachers’ creative autonomy support at both the individual and group level.

Results

The findings show that teachers in the intervention condition, compared to the control group, achieved a meaningful increase in their ability to offer creative autonomy support verbally. Teachers also showed development for the non-verbal and musical aspects of offering creative autonomy support. However, particularly for offering higher-level creative autonomy support in the non-verbal and musical mode, significant results were found for less than half of the intervention teachers.

Discussion

These results underline the importance of embracing and studying the bodily dimension as an integral part of teacher autonomy support, aimed at emergence of students’ musical creativity, in primary school music education and in teacher training. We explain how these results might be relevant for autonomy enhancing musical activities in vulnerable groups.
Anxiety in families of individuals with neurodevelopmental conditions in the early months of the COVID-19 pandemic in Switzerland
Authors: Di Poi Giona , Dukes Daniel , Meuleman Ben , Banta Lavenex Pamela , Lavenex Pierre , Papon Anouk , Tran Michel , Stallmann Lina , Treichel Noémie , Samson Andrea C.
Published: February 2023

In the spring of 2020, the COVID-19 pandemic generated a health, social, political, and economic crisis that dramatically reduced the institutional support for families of individuals with neurodevelopmental conditions (NDCs). To understand how these families may have experienced and coped with the pandemic, we created an online questionnaire that reached more than 10,000 families in 78 countries. The current manuscript - framed within the International Classification of Functioning, Disability and Health (ICF-10) model - investigates the impact of specific health conditions and personal or environmental factors on the anxiety of families living in Switzerland during the early months of the pandemic. To assess how differences in anxiety over time were predicted by specific health conditions or personal and environmental factors, two separate multilevel analyses were conducted for parents and their children with NDCs (N = 256). First, results showed that only parents reported an increase in anxiety when the pandemic started. Second, concerns related to loss of institutional support and financial and economic problems were the most anxiety-provoking factors for parents, whereas parents reported that the most anxiety-provoking factor for children was their concern about becoming bored. Many parents may have struggled with economic problems and managed multiple extra roles and tasks in their daily lives because institutional support was no longer available. As reported by their parents, although individuals with NDCs did not show an increase in anxiety, they may have struggled with boredom. This result may represent the inability to engage in satisfactory activities in daily life associated with a partial unawareness of the pandemic and the respective protective measures. Further research should more thoroughly investigate the potential effects of the individual’s primary condition, presence and severity of intellectual disability and awareness of the pandemic on the anxiety of individuals with NDCs. Ultimately, we present a series of reflections and practical suggestions that could help guide policymakers in potential future periods of crisis, social estrangement, and distance learning.
Monitoring treatment in pediatric patients with 21-hydroxylase deficiency
Authors: Itonaga Tomoyo , Hasegawa Yukihiro
Published: February 2023

21-hydroxylase deficiency (21-OHD) is the most common form of congenital adrenal hyperplasia. In most developed countries, newborn screening enables diagnosis of 21-OHD in asymptomatic patients during the neonatal period. In addition, recent advances in genetic testing have facilitated diagnosing 21-OHD, particularly in patients with equivocal clinical information. On the other hand, many challenges related to treatment remain. The goals of glucocorticoid therapy for childhood 21-OHD are to maintain growth and maturation as in healthy children by compensating for cortisol deficiency and suppressing excess adrenal androgen production. It is not easy to calibrate the glucocorticoid dosage accurately for patients with 21-OHD. Auxological data, such as height, body weight, and bone age, are considered the gold standard for monitoring of 21-OHD, particularly in prepuberty. However, these data require months to a year to evaluate. Theoretically, biochemical monitoring using steroid metabolites allows a much shorter monitoring period (hours to days). However, there are many unsolved problems in the clinical setting. For example, many steroid metabolites are affected by the circadian rhythm and timing of medication. There is still a paucity of evidence for the utility of biochemical monitoring. In the present review, we have attempted to clarify the knowns and unknowns about treatment parameters in 21-OHD during childhood.
Optimal control of renewable energy communities with controllable assets
Authors: Aittahar Samy , de Villena Miguel Manuel , Derval Guillaume , Castronovo Michael , Boukas Ioannis , Gemine Quentin , Ernst Damien
Published: February 2023

Introduction: The control of Renewable Energy Communities (REC) with controllable assets (e.g., batteries) can be formalised as an optimal control problem. This paper proposes a generic formulation for such a problem whereby the electricity generated by the community members is redistributed using repartition keys. These keys represent the fraction of the surplus of local electricity production (i.e., electricity generated within the community but not consumed by any community member) to be allocated to each community member. This formalisation enables us to jointly optimise the controllable assets and the repartition keys, minimising the combined total value of the electricity bills of the members.

Methods: To perform this optimisation, we propose two algorithms aimed at solving an optimal open-loop control problem in a receding horizon fashion. Moreover, we also propose another approximated algorithm which only optimises the controllable assets (as opposed to optimising both controllable assets and repartition keys). We test these algorithms on Renewable Energy Communities control problems constructed from synthetic data, inspired from a real-life case of REC.

Results: Our results show that the combined total value of the electricity bills of the members is greatly reduced when simultaneously optimising the controllable assets and the repartition keys (i.e., the first two algorithms proposed).

Discussion: These findings strongly advocate the need for algorithms that adopt a more holistic standpoint when it comes to controlling energy systems such as renewable energy communities, co-optimising or jointly optimising them from both a traditional (very granular) control standpoint and a larger economic perspective.
Ecophysiological responses of seedlings of six dipterocarp species to short-term drought in Borneo
Authors: Ichie Tomoaki , Igarashi Shuichi , Tanimoto Tomoko , Inoue Yuta , Mohizah Mohamad , Kenzo Tanaka
Published: February 2023

To predict the dynamics of tropical rainforest ecosystems in response to climate change, it is necessary to understand the drought tolerance and related mechanisms of trees in tropical rainforests. In this study, we assessed the ecophysiological responses of seedlings of six dipterocarp species (Dipterocarpus pachyphyllus, Dryobalanops aromatica, Shorea beccariana, S. curtisii, S. parvifolia, and S. smithiana) to experimental short-term drought conditions. The seedlings were initially grown in plastic pots with sufficient irrigation; irrigation was then stopped to induce drought. Throughout the soil-drying period, we measured various ecophysiological parameters, such as maximum photosynthetic and transpiration rates, stomatal conductance, water-use efficiency, predawn water potential, the maximum quantum yield of photosystem II (Fv/Fm), leaf water characteristics (using pressure-volume curves), leaf water content, and total sugar and starch contents. In all six dipterocarp species studied, the Fv/Fm values dropped sharply when the soil water content fell below 8%. However, there were interspecific differences in physiological responses to such a decrease in soil water content: S. parvifolia and S. beccariana actively controlled their stomata during drought to reduce water consumption via an isohydric response, but showed an increase (S. parvifolia) or no change (S. beccariana) in leaf drought tolerance; Di. pachyphyllus and Dry. aromatica maintained photosynthesis and transpiration close to the wilting point during drought without reducing water consumption via an anisohydric response, and also increased their leaf drought tolerance over the drying period; and S. curtisii and S. smithiana maintained their photosynthetic capacity without stomatal closure, but showed no change or a slight decrease in leaf drought tolerance. Our results indicate that extreme drought can cause the death of dipterocarp seedlings via various drought response, which could substantially impact the future distribution, population dynamics, and structure of tropical rainforests.
Smoking, alcohol consumption, and frailty: A Mendelian randomization study
Authors: Lv Jiannan , Wu Lianghua , Sun Sheng , Yu Huifang , Shen Zekai , Xu Jun , Zhu Jiahao , Chen Dingwan , Jiang Minmin
Published: February 2023

Background: Tobacco smoking and alcohol consumption have been associated with frailty in observational studies. We sought to examine whether these associations reflect causality using the two-sample Mendelian randomization (MR) design.

Methods: We used summary genome-wide association statistics for smoking initiation (N = 2,669,029), alcohol consumption (N = 2,428,851), and the frailty index (FI, N = 175,226) in participants of European ancestry. Both univariable and multivariable MR were performed to comprehensively evaluate the independent effects of smoking and alcohol consumption on the FI, accompanied by multiple sensitivity analyses. Results were verified using lifetime smoking and alcohol use disorder. Reverse direction MR was undertaken to assess the potential for reverse causation.

Results: Genetic predisposition to smoking initiation was significantly associated with increased FI (univariable MR: β = 0.345; 95% confidence interval [CI] = 0.316 to 0.374; p = 1.36E-113; multivariable MR: β = 0.219; 95% CI = 0.197 to 0.241; p = 2.44E-83). Genetically predicted alcohol consumption showed a suggestive association with the FI (univariable MR: β = −0.090; 95% CI = −0.151 to −0.029; p = 0.003; multivariable MR β = −0.153; 95% CI = −0.212 to −0.094; p = 2.03E-07), with inconsistent results in sensitivity analyses. In complementary analysis, genetic predicted lifetime smoking, but not alcohol use disorder was associated with the FI. There is no convincing evidence for reverse causation.

Conclusion: The present MR study supported smoking as a causal risk factor of frailty. Further research is warranted to investigate whether alcohol consumption has a causal role in frailty.
Identification and verification of m7G-Related genes as biomarkers for prognosis of sarcoma
Authors: Qin Haotian , Sheng Weibei , Weng Jian , Li Guoqing , Chen Yingqi , Zhu Yuanchao , Wang Qichang , Chen Yixiao , Yang Qi , Yu Fei , Zeng Hui , Xiong Ao
Published: February 2023

Background: Increasing evidence indicates a crucial role for N7-methylguanosine (m7G) methylation modification in human disease development, particularly cancer, and aberrant m7G levels are closely associated with tumorigenesis and progression via regulation of the expression of multiple oncogenes and tumor suppressor genes. However, the role of m7G in sarcomas (SARC) has not been adequately evaluated.

Materials and methods: Transcriptome and clinical data were gathered from the TCGA database for this study. Normal and SARC groups were compared for the expression of m7G-related genes (m7GRGs). The expression of m7GRGs was verified using real-time quantitative PCR (RT-qPCR) in SARC cell lines. Then, differentially expressed genes (DEGs) were identified between high and low m7GRGs expression groups in SARC samples, and GO enrichment and KEGG pathways were evaluated. Next, prognostic values of m7GRGs were evaluated by Cox regression analysis. Subsequently, a prognostic model was constructed using m7GRGs with good prognostic values by Lasso regression analysis. Besides, the relationships between prognostic m7GRGs and immune infiltration, clinical features, cuproptosis-related genes, and antitumor drugs were investigated in patients with SARC. Finally, a ceRNA regulatory network based on m7GRGs was constructed.

Results: The expression of ten m7GRGs was higher in the SARC group than in the control group. DEGs across groups with high and low m7GRGs expression were enriched for adhesion sites and cGMP-PKG. Besides, we constructed a prognostic model that consists of EIF4A1, EIF4G3, NCBP1, and WDR4 m7GRGs for predicting the survival likelihood of sarcoma patients. And the elevated expression of these four prognostic m7GRGs was substantially associated with poor prognosis and elevated expression in SARC cell lines. Moreover, we discovered that these four m7GRGs expressions were negatively correlated with CD4+ T cell levels, dendritic cell level and tumor purity, and positively correlated with tumor mutational burden, microsatellite instability, drug sensitivity and cuproptosis-related genes in patients with sarcomas. Then, a triple regulatory network of mRNA, miRNA, and lncRNA was established.

Conclusion: The current study identified EIF4A1, EIF4G3, NCBP1, and WDR4 as prognostic genes for SARC that are associated with m7G.These findings extend our knowledge of m7G methylation in SARC and may guide the development of innovative treatment options.
Gene expression signature of human neuropathic pain identified through transcriptome analysis
Authors: Hu Ling , Yin Wei , Ma Yao , Zhang Qiushi , Xu Qingbang
Published: February 2023

Introduction: Neuropathic pain is a type of chronic pain that is characterized by ongoing discomfort and can be challenging to manage effectively. This study aimed to identify genes associated with neuropathic pain through transcriptome analysis in order to gain a better understanding of the mechanisms underlying this chronic, difficult-to-treat pain.

Methods: We conducted transcriptome analysis using a training datasetof 202 individuals, including patients with neuropathic pain and healthy controls.

Results: Our analysis identified five genes (GTF2H2, KLHL5, LRRC37A4P, PRR24, and MRPL23) that were significantly differentially expressed in the tissue of patients with neuropathic pain compared to controls. We constructed a neuropathic pain signature using these five genes and validated it using an independent dataset of 25 individuals. Receiver operating characteristic (ROC) curve analysis demonstrated that this signature had a high level of accuracy in differentiating between neuropathic pain patients and healthy controls, with an area under the curve (AUC) of 0.83 (95% CI 0.65–1).

Discussion: These findings suggest that these five genes may be potential therapeutic targets for neuropathic pain.
piRNA pathway evolution beyond gonad context: Perspectives from apicomplexa and trypanosomatids
Authors: Horjales S. , Li Calzi M , Francia M. E. , Cayota A. , Garcia-Silva M. R.
Published: February 2023

piRNAs function as genome defense mechanisms against transposable elements insertions within germ line cells. Recent studies have unraveled that piRNA pathways are not limited to germ cells as initially reckoned, but are instead also found in non-gonadal somatic contexts. Moreover, these pathways have also been reported in bacteria, mollusks and arthropods, associated with safeguard of genomes against transposable elements, regulation of gene expression and with direct consequences in axon regeneration and memory formation. In this Perspective we draw attention to early branching parasitic protozoa, whose genome preservation is an essential function as in late eukaryotes. However, little is known about the defense mechanisms of these genomes. We and others have described the presence of putative PIWI-related machinery members in protozoan parasites. We have described the presence of a PIWI-like protein in Trypanosoma cruzi, bound to small non-coding RNAs (sRNAs) as cargo of secreted extracellular vesicles relevant in intercellular communication and host infection. Herein, we put forward the presence of members related to Argonaute pathways in both Trypanosoma cruzi and Toxoplasma gondii. The presence of PIWI-like machinery in Trypansomatids and Apicomplexa, respectively, could be evidence of an ancestral piRNA machinery that evolved to become more sophisticated and complex in multicellular eukaryotes. We propose a model in which ancient PIWI proteins were expressed broadly and had functions independent of germline maintenance. A better understanding of current and ancestral PIWI/piRNAs will be relevant to better understand key mechanisms of genome integrity conservation during cell cycle progression and modulation of host defense mechanisms by protozoan parasites.
Breastfeeding grief after chest masculinisation mastectomy and detransition: A case report with lessons about unanticipated harm
Authors: Gribble Karleen D. , Bewley Susan , Dahlen Hannah G.
Published: February 2023

An increasing number of young females are undergoing chest masculinsation mastectomy to affirm a gender identity and/or to relieve gender dysphoria. Some desist in their transgender identification and/or become reconciled with their sex, and then revert (or detransition). To the best of our knowledge, this report presents the first published case of a woman who had chest masculinisation surgery to affirm a gender identity as a trans man, but who later detransitioned, became pregnant and grieved her inability to breastfeed. She described a lack of understanding by maternity health providers of her experience and the importance she placed on breastfeeding. Subsequent poor maternity care contributed to her distress. The absence of breast function as a consideration in transgender surgical literature is highlighted. That breastfeeding is missing in counselling and consent guidelines for chest masculinisation mastectomy is also described as is the poor quality of existing research on detransition rates and benefit or otherwise of chest masculinising mastectomy. Recommendations are made for improving maternity care for detransitioned women1. Increasing numbers of chest masculinsation mastectomies will likely be followed by more new mothers without functioning breasts who will require honest, knowledgeable, and compassionate support.
Determinants of B-Cell Compartment Hyperactivation in European Adolescents Living With Perinatally Acquired HIV-1 After Over 10 Years of Suppressive Therapy
Authors: Ruggiero Alessandra , Pascucci Giuseppe Rubens , Cotugno Nicola , Domínguez-Rodríguez Sara , Rinaldi Stefano , Tagarro Alfredo , Rojo Pablo , Foster Caroline , Bamford Alasdair , De Rossi Anita , Nastouli Eleni , Klein Nigel , Morrocchi Elena , Fatou Benoit , Smolen Kinga K. , Ozonoff Al , Di Pastena Michela , Luzuriaga Katherine , Steen Hanno , Giaquinto Carlo , Goulder Philip , Rossi Paolo , Levy Ofer , Pahwa Savita , Palma Paolo ,   the EPIICAL Consortium
Published: February 2023

Background

Despite a successful antiretroviral therapy (ART), adolescents living with perinatally acquired HIV (PHIV) experience signs of B-cell hyperactivation with expansion of ‘namely’ atypical B-cell phenotypes, including double negative (CD27-IgD-) and termed age associated (ABCs) B-cells (T-bet+CD11c+), which may result in reduced cell functionality, including loss of vaccine-induced immunological memory and higher risk of developing B-cells associated tumors. In this context, perinatally HIV infected children (PHIV) deserve particular attention, given their life-long exposure to chronic immune activation.

Methods

We studied 40 PHIV who started treatment by the 2nd year of life and maintained virological suppression for 13.5 years, with 5/40 patients experiencing transient elevation of the HIV-1 load in the plasma (Spike). We applied a multi-disciplinary approach including immunological B and T cell phenotype, plasma proteomics analysis, and serum level of anti-measles antibodies as functional correlates of vaccine-induced immunity.

Results

Phenotypic signs of B cell hyperactivation were elevated in subjects starting ART later (%DN T-bet+CD11c+ p=0.03; %AM T-bet+CD11c+ p=0.02) and were associated with detectable cell-associated HIV-1 RNA (%AM T-bet+CD11c+ p=0.0003) and transient elevation of the plasma viral load (spike). Furthermore, B-cell hyperactivation appeared to be present in individuals with higher frequency of exhausted T-cells, in particular: %CD4 TIGIT+ were associated with %DN (p=0.008), %DN T-bet+CD11c+ (p=0.0002) and %AM T-bet+CD11c+ (p=0.002) and %CD4 PD-1 were associated with %DN (p=0.048), %DN T-bet+CD11c+ (p=0.039) and %AM T-bet+CD11c+ (p=0.006). The proteomic analysis revealed that subjects with expansion of these atypical B-cells and exhausted T-cells had enrichment of proteins involved in immune inflammation and complement activation pathways. Furthermore, we observed that higher levels of ABCs were associated a reduced capacity to maintain vaccine-induced antibody immunity against measles (%B-cells CD19+CD10- T-bet+, p=0.035).

Conclusion

We identified that the levels of hyperactivated B cell subsets were strongly affected by time of ART start and associated with clinical, viral, cellular and plasma soluble markers. Furthermore, the expansion of ABCs also had a direct impact on the capacity to develop antibodies response following routine vaccination.
Effect of extracorporeal hemoadsorption in critically ill patients with COVID-19: A narrative review
Authors: Chang Kaixi , Li Yupei , Qin Zheng , Zhang Zhuyun , Wang Liya , Yang Qinbo , Geng Jiwen , Deng Ningyue , Chen Shanshan , Su Baihai
Published: February 2023

COVID-19 has been affecting the world unprecedentedly and will remain widely prevalent due to its elusive pathophysiological mechanism and the continuous emergence of new variants. Critically ill patients with COVID-19 are commonly associated with cytokine storm, multiple organ dysfunction, and high mortality. To date, growing evidence has shown that extracorporeal hemoadsorption can exert its adjuvant effect to standard of care by regulating immune homeostasis, reducing viremia, and decreasing endotoxin activity in critically ill COVID-19 cases. However, the selection of various hemofilters, timing of initiation and termination of hemoadsorption therapy, anticoagulation management of extracorporeal circuits, identification of target subgroups, and ultimate survival benefit remain controversial. The purpose of this narrative review is to comprehensively summarize the rationale for the use of hemoadsorption in critically ill patients with COVID-19 and to gather the latest clinical evidence in this field.
NOX2 inhibition enables retention of the circadian clock in BV2 microglia and primary macrophages
Authors: Muthukumarasamy Iswarya , Buel Sharleen M. , Hurley Jennifer M. , Dordick Jonathan S.
Published: February 2023

Introduction

Sustained neuroinflammation is a major contributor to the progression of neurodegenerative diseases such as Alzheimer’s (AD) and Parkinson’s (PD) diseases. Neuroinflammation, like other cellular processes, is affected by the circadian clock. Microglia, the resident immune cells in the brain, act as major contributors to neuroinflammation and are under the influence of the circadian clock. Microglial responses such as activation, recruitment, and cytokine expression are rhythmic in their response to various stimuli. While the link between circadian rhythms and neuroinflammation is clear, significant gaps remain in our understanding of this complex relationship. To gain a greater understanding of this relationship, the interaction between the microglial circadian clock and the enzyme NADPH Oxidase Isoform 2 (NOX2) was studied; NOX2 is essential for the production of reactive oxygen species (ROS) in oxidative stress, an integral characteristic of neuroinflammation.

Methods

BV2 microglia were examined over circadian time, demonstrating oscillations of the clock genes Per2 and Bmal1 and the NOX2 subunits gp91phox and p47phox.

Results

The BV2 microglial clock exerted significant control over NOX2 expression and inhibition of NOX2 enabled the microglia to retain a functional circadian clock while reducing levels of ROS and inflammatory cytokines. These trends were mirrored in mouse bone marrow-derived primary macrophages.

Conclusions

NOX2 plays a crucial role in the interaction between the circadian clock and the activation of microglia/macrophages into their pro-inflammatory state, which has important implications in the control of neuroinflammation.
Drosophila Ectoderm-expressed 4 modulates JAK/STAT pathway and protects flies against Drosophila C virus infection
Authors: Huang Zongliang , Wang Wei , Xu Pengpeng , Gong Shangyu , Hu Yingshan , Liu Yan , Su Fang , Anjum Khalid Mahmood , Deng Wu-Min , Yang Suping , Liu Jiyong , Jiao Renjie , Chen Jianming
Published: February 2023

Sterile alpha and HEAT/Armadillo motif-containing protein (SARM) is conserved in evolution and negatively regulates TRIF-dependent Toll signaling in mammals. The SARM protein from Litopenaeus vannamei and its Drosophila orthologue Ectoderm-expressed (Ect4) are also involved in immune defense against pathogen infection. However, the functional mechanism of the protective effect remains unclear. In this study, we show that Ect4 is essential for the viral load in flies after a Drosophila C virus (DCV) infection. Viral load is increased in Ect4 mutants resulting in higher mortality rates than wild-type. Overexpression of Ect4 leads to a suppression of virus replication and thus improves the survival rate of the animals. Ect4 is required for the viral induction of STAT-responsive genes, TotA and TotM. Furthermore, Ect4 interacts with Stat92E, affecting the tyrosine phosphorylation and nuclear translocation of Stat92E in S2 cells. Altogether, our study identifies the adaptor protein Ect4 of the Toll pathway contributes to resistance to viral infection and regulates JAK/STAT signaling pathway.
RNA sequencing provides insights into the effect of dietary ingestion of microplastics and cadmium in the sea cucumber Apostichopus japonicus
Authors: Zhang Chenxi , Zhang Libin , Li Lingling , Mohsen Mohamed , Su Fang , Wang Xu , Lin Chenggang
Published: February 2023

Introduction

Microplastics (MPs) and cadmium (Cd) are persistent pollutants in aquatic environments. Sea cucumbers are susceptible to MPs and Cd due to their feeding behavior.

Methods

This study, based on Illumina sequencing, compared the transcriptomes of A. japonicus before and after Cd and/or MPs exposure. Additionally, we detected the changes of catalase (CAT), and superoxide dismutase (SOD) activity, glutathione (GSH), and malondialdehyde (MDA) content in sea cucumbers.

Results and Discussion

High concentration of MPs caused the increase of SOD activity. High concentration combined treatment resulted in significant up regulation of these four indicators in A. japonicus and had the largest number of differential expression genes (DEGs) reaching 1,618 DEGs, consisting of 789 up regulated along with 829 down regulated DEGs. Transcriptome results showed that Cd induced up regulation of intestinal FAS associated death domain protein (FADD) expression, which may cause apoptosis and inflammation. The increase of intestinal putative heparan sulfate 2-O-sulfotransferase in cadmium treatment groups provided a mechanism for host defense. The imbalance of expression of the NOD-like receptor (NLR) family inflammatory bodies and caspase 6 in the microplastic treatment group also led to the inflammatory reaction in the intestine of sea cucumber. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that in the process of fatty acid metabolism, MPs and Cd showed antagonistic effects, mainly in the inconsistent expression of Stearoyl CoA Ddesaturase (SCD1) protein. The significant changes of Toll interacting protein (TOLLIP) and E-selectin (SELE) in all Cd and MPs treatment groups may indicate the key immune response genes of sea cucumber to Cd exposure and MPs exposure. These genes were involved in the immune defense of sea cucumber exposed to different levels of Cd and MPs. This study provided insights into the mechanism of dietary MPs and Cd intake in an economically and ecologically important invertebrate species.
Does pronator quadratus repair affect functional outcome following volar plate fixation of distal radius fractures? A systematic review and meta-analysis
Authors: Ying Liwei , Cai Guoping , Zhu Zhong , Yu Guoliang , Su Yongwei , Luo Hua
Published: February 2023

Introduction

The study aimed to evaluate the efficacy of pronator quadratus (PQ) repair versus no repair following volar plate fixation of distal radius fractures.

Methods

A comprehensive search was performed in PubMed, CNKI, EMBASE, Web of Science, Ovid, and Cochrane Library databases. All randomized controlled trials comparing PQ repair with no repair in distal radius fractures before January 2023 were included. Two investigators independently screened eligible articles, assessed the study quality, and extracted data from included studies. Continuous variables used standardized mean difference and 95% confidence interval as efficacy statistics. The meta-analysis was performed using the Revman 5.4 software.

Results

A total of 430 patients in 7 RCT studies were included in this meta-analysis, of which 218 underwent PQ repair, while 212 patients underwent no repair. The results of the meta-analysis displayed statistically significant differences in grip strength (short-term), pronation angle (short-term), and pronation strength (short- and long-term) between the two groups. No significant difference in other outcomes was found between the two treatment arms.

Discussion

The repair of PQ may further increase grip strength and pronation function in the short-term and enhance long-term pronator muscle strength compared to no repair. However, due to the small number of articles included in the study, the above conclusions need to be verified by a larger sample and multi-center clinical study.
Morphological characteristics and phylogenetic analyses revealed four new species of Agaricales from China
Authors: Xu Jize , Jiang Yi , Wang Tiantian , Zhang Di , Li Xiaobin , Hosen Md. Iqbal
Published: February 2023

Four new species of Agaricales from China viz. Hohenbuehelia tomentosa, Rhodophana qinghaiensis, Rhodophana aershanensis, and Spodocybe tomentosum are described based on their unique morphological features and molecular evidence. Hohenbuehelia tomentosa is mainly characterized by its dark brown pileus with finely dense pure white tomentum, dirty white, decurrent lamellae, eccentric stipe, smooth spores, and fusiform metuloid cystidia. The characteristics of Rhodophana qinghaiensis are glabrous, smooth, reddish-brown pileus, gray-orange lamellae, and initially light orange becoming reddish brown stipe. The unique morphological characteristics of Rhodophana aershanensis are reddish brown pileus with age, brown-orange toward the margin, light orange lamellae and stipe dark brown at first, and reddish-brown with age. Spodocybe tomentosum is characterized by subclitocyboid and small basidiomes, finely dense pure white tomentum on the pileus surface, and broadly ellipsoid to ellipsoid and smaller basidiospores. Phylogenetic analysis showed that Hohenbuehelia tomentosa, Rhodophana qinghaiensis, Rhodophana aershanensis, and Spodocybe tomentosum formed an independent lineage. Full descriptions, illustrations, and phylogenetic trees of the four new species are provided in this study.
Specialized pro-resolving lipid mediators regulate inflammatory macrophages: A paradigm shift from antibiotics to immunotherapy for mitigating COVID-19 pandemic
Authors: Kumar Vikram , Yasmeen Nusrath , Chaudhary Anis Ahmad , Alawam Abdullah S. , Al-Zharani Mohammed , Suliman Basher Nosiba , Harikrishnan S. , Goud Muddapuram Deeksha , Pandey Aishwarya , Lakhawat Sudarshan Singh , Sharma Pushpender Kumar
Published: February 2023

The most severe clinical manifestations of the horrifying COVID-19 disease, that claimed millions of lives during the pandemic time, were Acute respiratory distress syndrome (ARDS), Coagulopathies, septic shock leading eventually to death. ARDS was a consequence of Cytokine storm. The viral SARS-COV2infection lead to avalanche of cytokines and eicosanoids causing “cytokine storm” and “eicosanoid storm.” Cytokine storm is one of the macrophage-derived inflammatory responses triggered by binding of virus particles to ACE2 receptors of alveolar macrophages, arise mainly due to over production of various pro-inflammatory mediators like cytokines, e.g., interleukin (IL)-1, IL-2, and tumor necrosis factor (TNF)- α, causing pulmonary edema, acute respiratory distress, and multi-organ failure. Cytokine storm was regarded as the predictor of severity of the disease and was deemed one of the causes of the high mortality rates due to the COVID-19. The basis of cytokine storm is imbalanced switching between an inflammation increasing - pro-inflammatory (M1) and an inflammation regulating-anti-inflammatory (M2) forms of alveolar macrophages which further deteriorates if opportunistic secondary bacterial infections prevail in the lungs. Lack of sufficient knowledge regarding the virus and its influence on co-morbidities, clinical treatment of the diseases included exorbitant use of antibiotics to mitigate secondary bacterial infections, which led to the unwarranted development of multidrug resistance (MDR) among the population across the globe. Antimicrobial resistance (AMR) needs to be addressed from various perspectives as it may deprive future generations of the basic health immunity. Specialized pro-resolving mediators (SPMs) are generated from the stereoselective enzymatic conversions of essential fatty acids that serve as immune resolvents in controlling acute inflammatory responses. SPMs facilitate the clearance of injured tissue and cell debris, the removal of pathogens, and augment the concentration of anti-inflammatory lipid mediators. The SPMs, e.g., lipoxins, protectins, and resolvins have been implicated in exerting inhibitory influence on with cytokine storm. Experimental evidence suggests that SPMS lower antibiotic requirement. Therefore, in this review potential roles of SPMs in enhancing macrophage polarization, triggering immunological functions, hastening inflammation resolution, subsiding cytokine storm and decreasing antibiotic requirement that can reduce AMR load are discussed.
Sequences of synaptogenesis in the human fetal and neonatal brain by synaptophysin immunocytochemistry
Authors: Sarnat Harvey B.
Published: February 2023

Synaptogenesis is the final phase of axonal pathfinding. Its sequences of spatial and temporal development in the immature nervous system are precisely timed and consistent. Synaptophysin, a principal structural glycoprotein of synaptic vesicle membranes regardless of the chemical transmitter substance within, is a reliable means of demonstrating sequences of synaptogenesis in human fetal brain tissue at autopsy and is resistant to postmortem autolysis. Furthermore, synaptophysin molecules are demonstrated during axoplasmic flow before being assembled into membranes in immature axons and also mature axons of neurons with a high metabolic rate. In brain malformations these sequences often are altered both in distribution of synapses and in timing, often delayed but sometimes precocious, with postnatal clinical manifestations such as epilepsy and cognitive development.