bluuebunny/crossref_metadata_2025 huggingface dataset:
Thinking Time, Shifting Goalposts and Ticking Time Bombs: Experiences of Waiting on the Gender Identity Development Service Waiting List
Authors: McKay Kathy , Kennedy Eilis , Wright Talen , Young Bridget
Published: October 2022

LOGiC-Q is a prospective longitudinal qualitative study that explores the experiences of children and young people, and their families, who have been referred to the Gender Identity Development Service (GIDS) in the UK. This paper describes the experiences of children and young people and their parents while they are on the waiting list to be seen. Semi-structured interviews were undertaken with 39 families who had been referred to GIDS and were waiting for their first appointment with the service. Both parent and child/young person were interviewed. Analysis of the anonymised interview transcripts was informed by both narrative and thematic approaches, and three predominant narratives around waiting were identified: 1. Positive experiences attached to waiting; 2. Feelings of distress and stuckness; 3. Suggestions for support while waiting. Findings from this study indicate variations in how waiting is experienced depending on the age of the child, and how distressed their body makes them feel. Young people and their parents offered suggestions for how the service could support families on the waiting list. These suggestions related primarily to ways of checking in and providing reassurance that they were at least still on the list as well as ideas about how to make the wait less distressing, rather than necessarily making the wait shorter, which was more spoken about in terms of an ideal rather than a realistic option.
Variables Influencing the Pressure and Volume of the Pulmonary Circulation as Risk Factors for Developing High Altitude Pulmonary Edema (HAPE)
Authors: Hundt Nina , Apel Christian , Bertsch Daniela , Cerfontaine Carina , van der Giet Michael , van der Giet Simone , Graß Maren , Haunolder Miriam , Heussen Nikole M. , Jäger Julia , Kühn Christian , Morrison Audry , Museo Sonja , Timmermann Lisa , Wernitz Knut , Gieseler Ulf , Küpper Thomas
Published: October 2022

Background: At altitudes above 2500 m, the risk of developing high altitude pulmonary edema (HAPE) grows with the increases in pulmonary arterial pressure. HAPE is characterized by severe pulmonary hypertension, though the incidence and relevance of individual risk factors are not yet predictable. However, the systolic pulmonary pressure (SPAP) and peak in tricuspid regurgitation velocity (TVR) are crucial factors when diagnosing pulmonary hypertension by echocardiography. Methods: The SPAP and TVR of 27 trekkers aged 20–65 years en route to the Solu Khumbu region of Nepal were assessed. Echocardiograph measurements were performed at Lukla (2860 m), Gorak Shep (5170 m), and the summit of Kala Patthar (5675 m). The altitude profile and the participants’ characteristics were also compiled for correlation with the measured data. Results: The results showed a highly significant increase in SPAP and TVR after ascending Kala Patthar. The study revealed a lower increase of SPAP and TVR in the group of older participants, although the respective initial measurements at Gorak Shep were significantly higher for this group. A similar finding occurred in those using Diamox® as prophylaxis. There was an inverse relationship between TVR and SPAP, the peripheral capillary oxygen saturation, and heart rate. Conclusions: The echocardiograph results indicated that older people are an at-risk group for developing HAPE. A conservative interpretation of the basic tactical rules for altitudes should be followed for older trekkers or trekkers with known problems of altitude acclimatization (“slow acclimatizer”) as SPAP elevates with age. The prophylactic use of Acetazolamide (Diamox®) should be avoided where not necessary for acute medical reasons. Acetazolamide leads to an increase of SPAP, and this may potentially enhance the risk of developing HAPE. Arterial oxygen saturation measurements can provide an indicator for the self-assessment for the risk of developing HAPE and a rule of thumb for the altitude profile, but does not replace a HAPE diagnosis. Backpack weight, sex, workload (actual ascent speed), and pre-existing diseases were not statistically significant factors related to SPAP and TVR (p ≤ 0.05).
Perception and Acceptance of Using Different Generic Types of COVID-19 Vaccine, the “Mix-and-Match” Strategy, in Saudi Arabia: Cross-Sectional Web-Based Survey
Authors: Alqurashi Afnan , Sindy Enas A. , Dosh Heba , Khayat Sumaya Z. , Alqarna Lujain M. , Sodagar Wafa M. , Samannodi Mohammed , Alwafi Hassan , Salawati Emad , Almatrafi Mohammed A. , Ekram Rakan , Bagadood Rehab M. , Alsafi Radi , Assaggaf Hamza M.
Published: October 2022

Background: Soon after the COVID-19 pandemic was declared, a pharmaceutical company expressed rapid interest in developing a safe and effective vaccine candidate to contain the spread of SARS-CoV-2 infections. The FDA approved the Pfizer-BioNTech, AstraZeneca, Moderna, and Janssen vaccines. Here, we investigated the attitude and acceptance of using different generic types of COVID-19 vaccines in Saudi Arabia. Methods: This study is a cross-sectional study using an online survey conducted in Saudi Arabia from the 19th of October to the 6th of December 2021. The questionnaire was distributed using social media platforms such as Twitter, WhatsApp, and Facebook. The inclusion criteria to participate in this study were adults who live in Saudi Arabia (Saudis or non-Saudis) and had two doses of COVID-19 vaccinations. Result: 3486 participants were included in this study, and 67.5% of the participants had side effects after the first dose. Similarly, 66.7% of the study participants had side effects after administering the second dose. Our data showed that most participants were unsure if the heterologous COVID-19 vaccination could cause severe side effects. In addition, 47.6% of the participants refused to receive a different generic type of COVID-19 vaccine due to fear of health problems. However, most participants obtained information regarding COVID-19 vaccination from the Saudi Ministry of Health. Conclusions: We found a low level of acceptance for receiving different generic types of vaccines if the participants had a choice. Therefore, plans should focus on increasing the acceptance level among the Saudi population through official platforms such as the Saudi Ministry of Health and private clinics.
Analysis of Blood Biochemistry and Pituitary-Gonadal Histology after Chronic Exposure to Bisphenol-A of Mice
Authors: Molina-López Ana M. , Bujalance-Reyes Francisca , Urbano María Teresa , Lora-Benítez Antonio , Ayala-Soldado Nahúm , Moyano-Salvago Rosario
Published: October 2022

Bisphenol-A is an emerging pollutant that is widespread in the environment, and to which live beings are continuously and inadvertently exposed. It is a substance with an endocrine-disrupting capacity, causing alterations in the reproductive, immunological, and neurological systems, among others, as well as metabolic alterations. Our study aimed to assess its clinical signs, and effects on the most relevant blood biochemical parameters, and to evaluate pituitary and gonadal histology after a chronic exposure of adult mice to different BPA doses (0.5, 2, 4, 50 and 100 µg/kg BW/day) through their drinking water. The biochemical results showed that a marked significant reduction (p < 0.05) was produced in the levels of serum glucose, hypoproteinaemia and hypoalbuminemia in the groups exposed to the highest doses, whereas in the group exposed to 50 µg/kg BW/day the glucose and total protein levels dropped, and the animals exposed to 100 µg/kg BW/day experienced a diminution in albumin levels. In the case of the group exposed to 50 µg/kg BW/day, however, hypertriglyceridemia and hypercholesterolemia were determined, and the blood parameters indicating kidney alterations such as urea and creatinine experienced a significant increase (p < 0.05) with respect to the controls. Regarding the pituitary and gonads, none of the animals exposed presented histological alterations at the doses tested, giving similar images to those of the control group. These results suggest that continuous exposure to low BPA doses could trigger an inhibition of hepatic gluconeogenesis, which would result in a hypoglycaemic state, together with an induction of the enzymes responsible for lipidic synthesis, a mechanism by which the increase in the lipid and serum cholesterol levels could be explained. Likewise, the decline in the protein and albumin levels would be indicative of a possible hepatic alteration, and the increase in urea and creatinine would point to a possible renal perturbation, derived from continuous exposure to this xenobiotic. Based on our results, it could be said that chronic exposure to low BPA doses would not produce any clinical signs or histological pituitary-gonadal effects, but it could cause modifications in some blood biochemical parameters, that could initially indicate a possible hepatic and renal effect.
Spatiotemporal Dynamics of Carbon Footprint of Main Crop Production in China
Authors: Fan Jianling , Guo Dengwei , Han Lu , Liu Cuiying , Zhang Chuanhong , Xie Jianan , Niu Junzhao , Yin Liwen
Published: October 2022

As a major agricultural country, the comprehensive accounting of the dynamics and composition of the carbon footprint of major crops in China will provide a decision-making basis for environmental management and agricultural green development in the whole process of the major crop production system in China. To investigate the spatiotemporal dynamics of the carbon footprint for major crops in China, a life cycle-based carbon footprint approach was used to evaluate the carbon footprint per unit area (CFA) and per unit yield (CFY) of eight crops for the period of 1990 to 2019. Our results showed that the CFA for all major crops showed an increasing trend with time before 2016 but slowly decreased afterward, while the CFY decreased by 16–43% over the past 30 years due to the increase in crop yield. The three main grain crops, rice (4871 ± 418 kg CO2-eq · ha−1), wheat (2766 ± 552 kg CO2-eq · ha−1), and maize (2439 ± 530 kg CO2-eq · ha−1), showed the highest carbon footprint and contribution to the total greenhouse gas (GHG) emissions, mainly due to their larger cultivated areas and higher fertilizer application rates. CH4 emission was the major component of the carbon footprint for rice production, accounting for 66% and 48% of the CFA and CFY, respectively, while fertilizer production and usage were the largest components of carbon footprint for dryland crops, making up to 26–49% of the CFA and 26–50% of the CFY for different crops. The present study also highlighted the spatial and temporal patterns of the carbon footprint for major crops in China, which could serve as references for the development of best management practices for different crop production in China, to mitigate agricultural GHG emission and to pursue low-carbon agriculture.
Associations between Per- and Polyfluoroalkyl Substances (PFAS) and Cardiometabolic Biomarkers in Adults of Czechia: The Kardiovize Study
Authors: Maranhao Neto Geraldo A. , Polcrova Anna Bartoskova , Pospisilova Anna , Blaha Ludek , Klanova Jana , Bobak Martin , Gonzalez-Rivas Juan P.
Published: October 2022

Even though there is evidence of decreasing trends of per- and polyfluoroalkyl substances (PFAS) in Czechia, there are still major sources of PFAS pollution. Regarding the still-inconsistent results of the relationship between cardiometabolic health and PFAS, the present study sought to determine the association between PFAS levels and the presence of cardiometabolic biomarkers, including blood pressure and dysglycemia drivers in the Czech population. A cross-sectional study with 479 subjects (56.4% women, median: 53 years, range: 25–89) was conducted. Four PFAS were measured in serum: perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluorooctane sulfonate (PFOS). The associations between natural log (ln)-transformed PFAS and cardiometabolic biomarkers were assessed through generalized additive models using linear regression and smoothing thin plate splines, adjusted for potential confounders. There were positive and significant (p < 0.05) associations between the ln-transformed PFOA and glucose (β = 0.01), systolic (β = 0.76) and diastolic blood pressure (β = 0.65); total cholesterol (β = 0.07) and LDL-c (β = 0.04); and PFOS with glucose (β = 0.03), BMI (β = 2.26), waist circumference (β = 7.89), systolic blood pressure (β = 1.18), total cholesterol (β = 0.13), and HDL-c (β = 0.04). When significant, the correlations of PFNA and PFDA were negative. Of the four PFAS, only PFOA and PFOS showed a positive association, even in serum levels not as high as the values from the literature.
Does Exercise Training Improve Cardiac-Parasympathetic Nervous System Activity in Sedentary People? A Systematic Review with Meta-Analysis
Authors: Casanova-Lizón Antonio , Manresa-Rocamora Agustín , Flatt Andrew A. , Sarabia José Manuel , Moya-Ramón Manuel
Published: October 2022

The aim of this study was to investigate the training-induced effect on cardiac parasympathetic nervous system (PNS) activity, assessed by resting heart rate variability (HRV) and post-exercise heart rate recovery (HRR), in sedentary healthy people. Electronic searches were carried out in PubMed, Embase, and Web of Science. Random-effects models of between-group standardised mean difference (SMD) were estimated. Heterogeneity analyses were performed by means of the chi-square test and I2 index. Subgroup analyses and meta-regressions were performed to investigate the influence of potential moderator variables on the training-induced effect. The results showed a small increase in RMSSD (SMD+ = 0.57 [95% confidence interval (CI) = 0.23, 0.91]) and high frequency (HF) (SMD+ = 0.21 [95% CI = 0.01, 0.42]) in favour of the intervention group. Heterogeneity tests reached statistical significance for RMSSD and HF (p ≤ 0.001), and the inconsistency was moderate (I2 = 68% and 60%, respectively). We found higher training-induced effects on HF in studies that performed a shorter intervention or lower number of exercise sessions (p ≤ 0.001). Data were insufficient to investigate the effect of exercise training on HRR. Exercise training increases cardiac PNS modulation in sedentary people, while its effect on PNS tone requires future study.
Weight Control Registry Using Korean Medicine: A Protocol for a Prospective Registry Study
Authors: Cha Jiyun , Ahn Eun Kyoung , Kim Min-Ji , Jung So-Young , Kim Ho-Seok , Kim Eunjoo , Sung Hyun-Kyung , Shin Seon Mi , Chung Won-Seok , Lee Jun-Hwan , Kim Hojun
Published: October 2022

Lifestyle and physical characteristics affect body weight, and understanding these factors improves the precision of weight loss treatment. Many obese patients in Korea are receiving Korean medicine (KM) treatment, including herbal medicine and acupuncture, for weight loss. However, the real-world data (RWD) are insufficient in terms of being longitudinal and diverse. Weight Control Registry using KM is a prospective registry study that enrolls patients receiving KM treatment for weight loss and collects RWD from multiple clinics. The patients who are eligible for this study are aged 19–65 years, receive KM weight loss treatment, understand the study objectives, and consent voluntarily. Clinical data of patient characteristics and KM treatment patterns will be regularly collected until 2026. The longitudinal accumulation of various RWD will establish a high-quality study database for KM weight loss treatment. With this study, we expect to contribute to understanding the current trend of weight loss treatment with KM and solve further questions regarding this treatment.
A 22-Site Comparison of Land-Use Practices, E-coli and Enterococci Concentrations
Authors: Hubbart Jason A. , Kellner Elliott , Petersen Fritz
Published: October 2022

Land-use practices can greatly impact water quality. Escherichia (E.) coli and Enterococcus are accepted water quality indicators. However, surprisingly little research has been conducted comparing both organisms’ population density relationships to land use practices and water quality. Stream water grab samples were collected monthly (n = 9 months) from 22 stream monitoring sites draining varying land use practice types in a representative mixed-land-use watershed of the northeastern United States. E. coli and enterococci colony forming units (CFU per 100 mL) were estimated (n = 396) and statistically analyzed relative to land use practices, hydroclimate, and pH, using a suite of methods, including correlation analysis, Principal Components Analysis (PCA), and Canonical Correspondence Analysis (CCA). Correlation analyses indicated significant (p < 0.05) relationships between fecal indicator bacteria concentrations, water quality metrics and land use practices but emphasized significant (p < 0.05) negative correlations between pH and instream enterococci concentrations. PCA and CCA results indicated consistent spatial differences between fecal indicator bacteria concentrations, pH, and land use/land cover characteristics. The study showed that pH could be considered an integrated proxy variable for past (legacy) and present land use practice influences. Results also bring to question the comparability of E-coli and enterococci relative to dominant land use practices and variations in pH and provide useful information that will help guide land use practice and water pollutant mitigation decision making.
The Feelings of Nursing Students during the COVID-19 Confinement: Narrative-Based Nursing and Poetry-of-Care Perspectives
Authors: Siles José , Andina-Díaz Elena , Solano-Ruíz Carmen
Published: October 2022

(1) Background: Experiences involve feelings, which, in turn, produce meaning that can become a subjectively lived experience. Therefore, the study of experiences and feelings is essential. Introduction: We examined the role of narrative-based nursing (NBN) and the poetry of care (PC). Objective: To reflect upon the emotions and feelings experienced by nursing students during confinement induced by COVID-19. (2) Methods: This is a qualitative study with a focus on reflexive anthropology, NBN, and PC. Setting and participants: The non-probabilistic sample of incidental, casual, or accessibility type. It consists of 198 students completing their first degree in nursing (the academic year of 2019-2020) of the University of Alicante. (3) Results: Three main categories were considered in the research: For the ‘first day’, 21 subcategories were identified, and uncertainty was the most frequently noted feeling. For the ‘most significant day’, 22 subcategories were found, with the explosion of feelings being the most frequent. For the ‘last day’, 15 subcategories were recorded, with the feeling of relief being the most common. Conclusions: The NBN and PC are relevant therapeutic tools that facilitate reflection and promote awareness of feelings.
Health Impacts of the COVID-19 Lockdown Measure in a Low Socio-Economic Setting: A Cross-Sectional Study on Reunion Island
Authors: Fianu Adrian , Aissaoui Hind , Naty Nadège , Lenclume Victorine , Casimir Anne-Françoise , Chirpaz Emmanuel , Maillard Olivier , Spodenkiewicz Michel , Bouscaren Nicolas , Kelly-Irving Michelle , Rachou Emmanuelle , Delpierre Cyrille , Gérardin Patrick
Published: October 2022

In March 2020, the French government implemented nation-wide measures to reduce social contact and slow the progression of the emerging coronavirus responsible for COVID-19, the most significant being a complete home lockdown that lasted 8 weeks. Reunion Island is a French overseas department marked by large social inequalities. We draw the hypothesis that distancing and lockdown measures may have contributed to an increase in the social inequalities in health (SIH) on Reunion Island. The aim of our study was to describe the SIH during lockdown in the Reunionese population. We implemented a cross-sectional telephone survey conducted between 13 May and 22 July 2020, using a retrospective data collection on the lockdown period. A total of 892 adult participants (≥18 years) were recruited in the 114 large Reunionese neighborhoods using the quota method within the national “White Pages” telephone directory. Degraded psychological states, an increase in addictive behaviors, difficulties in accessing food, a decrease in physical activity, delayed medical appointments, violence against women, and health problems in children were driven by the socio-economic characteristics of the population, most often to the disadvantage of social groups exposed to poor living conditions. These results suggest that the COVID-19 lockdown contributed to an increase in SIH.
Differences in Synovial Cytokine Profile Associated with Long-Term Clinical Outcomes in Patients with Knee Osteoarthritis Undergoing Corrective Osteotomy with Platelet-Rich Plasma or Stromal Vascular Fraction Post-Treatments
Authors: Prizov Aleksey , Tchetina Elena , Eremin Ilya , Zagorodniy Nikolay , Pulin Andrey , Belyak Evgeniy , Goncharov Evgeniy , Kotenko Konstantin , Smyshlyaev Ivan , Glukhova Svetlana , Lila Aleksandr
Published: October 2022

Functional outcomes and synovial fluid (SF) cytokine concentrations in response to platelet-rich plasma (PRP) or stromal vascular fraction (SVF) post-treatments following open wedge high tibial osteotomy (HTO) in 20 patients with knee osteoarthritis (OA) were examined. Six weeks after surgery, the knees of 10 patients were injected with autologous PRP (PRP subgroup), while another 10 patients were injected with autologous SVF (SVF subgroup) and monitored for 1.5 years. Pain assessment (VAS score) and functional activity (KOOS, KSS, Outerbridge, and Koshino scores) were applied. PRP subgroup performed better compared with the SVF subgroup according to KOOS, KSS, and VAS scores, while the SVF subgroup demonstrated better results according to Outerbridge and Koshino testing and produced more pronounced cartilage regeneration in the medial condyle and slowed down cartilage destruction in its lateral counterpart. SF was collected before and one week after PRP or SVF injections and tested for concentrations of 41 cytokines (Multiplex Assay). In the PRP subgroup, a significant decrease in IL-6 and CXCL10 synovial concentrations was accompanied by an increase in IL-15, sCD40L, and PDGF-AB/BB amounts. The SVF subgroup demonstrated a significant decrease in synovial TNFα, FLT-3L, MIP-1β, RANTES, and VEGF concentrations while SF concentrations of MCP-1 and FGF2 increased. Both post-treatments have a potential for increased tissue regeneration, presumably due to the downregulation of inflammation and augmentation of synovial growth factor concentrations.
Pediatric Multisystem Syndrome Associated with SARS-CoV-2 (MIS-C): The Interplay of Oxidative Stress and Inflammation
Authors: Perrone Serafina , Cannavò Laura , Manti Sara , Rullo Immacolata , Buonocore Giuseppe , Esposito Susanna Maria Roberta , Gitto Eloisa
Published: October 2022

Pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (MIS-C) is characterized by persistent fever and evidence of single or multiorgan dysfunction, and laboratory evidence of inflammation, elevated neutrophils, reduced lymphocytes, and low albumin. The pathophysiological mechanisms of MIS-C are still unknown. Proinflammatory mediators, including reactive oxygen species and decreased antioxidant enzymes, seems to play a central role. Virus entry activates NOXs and inhibits Nrf-2 antioxidant response inducing free radicals. The biological functions of nonphagocytic NOXs are still under study and appear to include: defense of epithelia, intracellular signaling mechanisms for growth regulation and cell differentiation, and post-translational modifications of proteins. This educational review has the aim of analyzing the newest evidence on the role of oxidative stress (OS) in MIS-C. Only by relating inflammatory mediators to OS evaluation in children following SARS-CoV-2 infection will it be possible to achieve a better understanding of these mechanisms and to reduce long-term morbidity. The link between inflammation and OS is key to developing effective prevention strategies with antioxidants to protect children.
Gut Microbiome Changes in Gestational Diabetes
Authors: Ionescu Ruxandra Florentina , Enache Robert Mihai , Cretoiu Sanda Maria , Gaspar Bogdan Severus
Published: October 2022

Gestational diabetes mellitus (GDM), one of the most common endocrine pathologies during pregnancy, is defined as any degree of glucose intolerance with onset or first discovery in the perinatal period. Physiological changes that occur in pregnant women can lead to inflammation, which promotes insulin resistance. In the general context of worldwide increasing obesity in young females of reproductive age, GDM follows the same ascending trend. Changes in the intestinal microbiome play a decisive role in obesity and the development of insulin resistance and chronic inflammation, especially in patients with type 2 diabetes mellitus (T2D). To date, various studies have also associated intestinal dysbiosis with metabolic changes in women with GDM. Although host metabolism in women with GDM has not been fully elucidated, it is of particular importance to analyze the available data and to discuss the actual knowledge regarding microbiome changes with potential impact on the health of pregnant women and newborns. We analyzed peer-reviewed journal articles available in online databases in order to summarize the most recent findings regarding how variations in diet and metabolic status of GDM patients can contribute to alteration of the gut microbiome, in the same way that changes of the gut microbiota can lead to GDM. The most frequently observed alteration in the microbiome of patients with GDM was either an increase of the Firmicutes phylum, respectively, or a decrease of the Bacteroidetes and Actinobacteria phyla. Gut dysbiosis was still present postpartum and can impact the development of the newborn, as shown in several studies. In the evolution of GDM, probiotic supplementation and regular physical activity have the strongest evidence of proper blood glucose control, favoring fetal development and a healthy outcome for the postpartum period. The current review aims to summarize and discuss the most recent findings regarding the correlation between GDM and dysbiosis, and current and future methods for prevention and treatment (lifestyle changes, pre- and probiotics administration). To conclude, by highlighting the role of the gut microbiota, one can change perspectives about the development and progression of GDM and open up new avenues for the development of innovative therapeutic targets in this disease.
miRNAs as Biomarkers in Diabetes: Moving towards Precision Medicine
Authors: Angelescu Maria Alexandra , Andronic Octavian , Dima Simona Olimpia , Popescu Irinel , Meivar-Levy Irit , Ferber Sarah , Lixandru Daniela
Published: October 2022

Diabetes mellitus (DM) is a complex metabolic disease with many specifically related complications. Early diagnosis of this disease could prevent the progression to overt disease and its related complications. There are several limitations to using existing biomarkers, and between 24% and 62% of people with diabetes remain undiagnosed and untreated, suggesting a large gap in current diagnostic practices. Early detection of the percentage of insulin-producing cells preceding loss of function would allow for effective therapeutic interventions that could delay or slow down the onset of diabetes. MicroRNAs (miRNAs) could be used for early diagnosis, as well as for following the progression and the severity of the disease, due to the fact of their pancreatic specific expression and stability in various body fluids. Thus, many studies have focused on the identification and validation of such groups or “signatures of miRNAs” that may prove useful in diagnosing or treating patients. Here, we summarize the findings on miRNAs as biomarkers in diabetes and those associated with direct cellular reprogramming strategies, as well as the relevance of miRNAs that act as a bidirectional switch for cell therapy of damaged pancreatic tissue and the studies that have measured and tracked miRNAs as biomarkers in insulin resistance are addressed.
The Impact of Sphingosine Kinases on Inflammation-Induced Cytokine Release and Vascular Endothelial Barrier Integrity
Authors: Thuy Andreas V. , Reimann Christina-Maria , Ziegler Anke C. , Gräler Markus H.
Published: October 2022

Sphingosine kinases type 1 and 2 (SphK1/2) are required for the production of the immune modulator sphingosine 1-phosphate (S1P). SphK1 deficient mice (SphK1−/−) revealed 50% reduced S1P in plasma, while SphK2−/− mice demonstrated 2–3 times increased S1P levels in plasma. Since plasma S1P is a potent inducer of vascular endothelial cell (VEC) barrier stability, we hypothesized that higher and lower levels of S1P in SphK2−/− and SphK1−/− mice, respectively, compared to wild type (wt) mice should translate into decreased and increased severity of induced systemic inflammation due to improved or damaged VEC barrier maintenance. To our surprise, both SphK1−/− and SphK2−/− mice showed improved survival rate and earlier recovery from inflammation-induced weight loss compared to wt mice. While no difference was observed in VEC barrier stability by monitoring Evans blue leakage into peripheral tissues, SphK1−/− mice demonstrated a distinct delay and SphK2−/− mice an improved resolution of early pro-inflammatory cytokine release in plasma. Ex vivo cell culture experiments demonstrated that bone marrow-derived dendritic cells (BMDC) generated from SphK1−/− and SphK2−/− mice responded with decreased interferon-γ (IFN-γ) production upon stimulation with lipopolysaccharides (LPS) compared to wt BMDC, while activation-induced cytokine expression of lymphocytes and macrophages was not majorly altered. Ex vivo stimulation of macrophages with IFN-γ resulted in increased cytokine release. These results suggest that SphK1/2 are involved in production and secretion of IFN-γ by DC. DC-derived IFN-γ subsequently stimulates the production and secretion of a large panel of inflammatory cytokines by macrophages, which belong to the main cytokine-releasing cells of the early innate immune response. Inhibitors of SphK1/2 may therefore be attractive targets to dampen the early cytokine response of macrophages as part of the innate immune response.
Clinical and Genetic Characteristics of a Cohort with Distal Vaginal Atresia
Authors: Kang Jia , Zhou Qing , Chen Na , Liu Zhongzhen , Zhang Ye , Sun Jinghua , Ma Congcong , Chen Fang , Ma Yidi , Wang Lin , Zhu Lan , Wang Wenjing
Published: October 2022

Distal vaginal atresia is a rare abnormality of female reproductive tract in which the vagina is closed or absent. The distal vagina may be replaced by fibrous tissue and the condition is often not diagnosed until a girl fails to begin having periods at puberty. Although it is a congenital disorder, potential genetic causes of distal vaginal atresia are still unknown. We recruited a cohort of 39 patients with distal vaginal atresia and analyzed their phenotypic and genetic features. In addition to the complaint of distal vaginal atresia, approximately 17.9% (7/39) of the patients had other Müllerian anomalies, and 17.9% (7/39) of the patients had other structural abnormalities, including renal-tract, skeletal and cardiac anomalies. Using genome sequencing, we identified two fragment duplications on 17q12 encompassing HNF1B and LHX1, two dosage-sensitive genes with candidate pathogenic variants, in two unrelated patients. A large fragment of uniparental disomy was detected in another patient, affecting genes involved in cell morphogenesis and connective tissue development. Additionally, we reported two variants on TBX3 and AXL, leading to distal vaginal atresia in mutated mouse model, in our clinical subjects for the first time. Essential biological functions of these detected genes with pathogenic variants included regulating reproductive development and cell fate and patterning during embryogenesis. We displayed the comprehensive clinical and genetic characteristic of a cohort with distal vaginal atresia and they were highly heterogeneous both phenotypically and genetically. The duplication of 17q12 in our cohort could help to expand its phenotypic spectrum and potential contribution to the distal vaginal atresia. Our findings of pathogenic genetic variants and associated phenotypes in our cohort could provide evidence and new insight for further research attempting to reveal genetic causes of distal vaginal atresia.
Neutrophils’ Extracellular Trap Mechanisms: From Physiology to Pathology
Authors: Schoen Janina , Euler Maximilien , Schauer Christine , Schett Georg , Herrmann Martin , Knopf Jasmin , Yaykasli Kursat Oguz
Published: October 2022

Neutrophils are an essential part of the innate immune system and the first line of defense against invading pathogens. They phagocytose, release granular contents, produce reactive oxygen species, and form neutrophil extracellular traps (NETs) to fight pathogens. With the characterization of NETs and their components, neutrophils were identified as players of the innate adaptive crosstalk. This has placed NETs at the center not only of physiological but also pathological processes. Aside from their role in pathogen uptake and clearance, NETs have been demonstrated to contribute to the resolution of inflammation by forming aggregated NETs able to degrade inflammatory mediators. On the other hand, NETs have the potential to foster severe pathological conditions. When homeostasis is disrupted, they occlude vessels and ducts, serve as sources of autoantigens and danger or damage associated molecular patterns, directly damage tissues, and exaggerate complement activity and inflammation. This review focusses on the understanding of NETs from their formation to their functions in both physiological and pathological processes.
Oxylipins Associated with D3-Creatine Muscle Mass/Weight and Physical Performance among Community-Dwelling Older Men
Authors: Marron Megan M. , Orwoll Eric S. , Cawthon Peggy M. , Lane Nancy E. , Newman Anne B. , Cauley Jane A.
Published: October 2022

Poor physical function is highly prevalent with aging, and strongly associated with D3-creatine muscle mass/weight. Using metabolomics, we previously identified several triglycerides consisting mostly of polyunsaturated fatty acids that were higher in older adults with good mobility. Here, we sought to further investigate polyunsaturated fatty-acid-related metabolites, i.e., oxylipins, and their associations with D3-creatine muscle mass/weight, gait speed, grip strength, and the Short Physical Performance Battery among 463 older men from the Osteoporotic Fractures in Men Study (MrOS). Oxylipins were measured in fasting serum using liquid chromatography–mass spectrometry. Muscle mass was estimated using D3-creatine dilution and adjusted for body size. We used linear regression to determine oxylipins associated with D3-creatine muscle mass/weight and physical performance, while adjusting for age, education, physical activity, Western dietary pattern, fish oil supplementation, and multiple comparisons. Among 42 oxylipins, none were associated with grip strength and 3 were associated with the Short Physical Performance Battery. In contrast, 18 and 17 oxylipins were associated with D3-creatine muscle mass/weight and gait speed, respectively. A subset of associations between oxylipins and gait speed were partially attenuated by D3-creatine muscle mass/weight. Higher levels of fatty acid alcohol and ketone oxylipins tended to be most strongly associated with gait speed and D3-creatine muscle mass/weight, potentially reflecting anti-inflammatory activity from these select oxylipins in MrOS older men.
The Shift in Synonymous Codon Usage Reveals Similar Genomic Variation during Domestication of Asian and African Rice
Authors: Xiao Guilian , Zhou Junzhi , Huo Zhiheng , Wu Tong , Li Yingchun , Li Yajing , Wang Yanxia , Wang Mengcheng
Published: October 2022

The domestication of wild rice occurred together with genomic variation, including the synonymous nucleotide substitutions that result in synonymous codon usage bias (SCUB). SCUB mirrors the evolutionary specialization of plants, but its characteristics during domestication were not yet addressed. Here, we found cytosine- and guanidine-ending (NNC and NNG) synonymous codons (SCs) were more pronounced than adenosine- and thymine-ending SCs (NNA and NNT) in both wild and cultivated species of Asian and African rice. The ratios of NNC/G to NNA/T codons gradually decreased following the rise in the number of introns, and the preference for NNA/T codons became more obvious in genes with more introns in cultivated rice when compared with those in wild rice. SCUB frequencies were heterogeneous across the exons, with a higher preference for NNA/T in internal exons than in terminal exons. The preference for NNA/T in internal but not terminal exons was more predominant in cultivated rice than in wild rice, with the difference between wild and cultivated rice becoming more remarkable with the rise in exon numbers. The difference in the ratios of codon combinations representing DNA methylation-mediated conversion from cytosine to thymine between wild and cultivated rice coincided with their difference in SCUB frequencies, suggesting that SCUB reveals the possible association between genetic and epigenetic variation during the domestication of rice. Similar patterns of SCUB shift in Asian and African rice indicate that genomic variation occurs in the same non-random manner. SCUB representing non-neutral synonymous mutations can provide insight into the mechanism of genomic variation in domestication and can be used for the genetic dissection of agricultural traits in rice and other crops.
Genome-Wide Identification and Variation Analysis of JAZ Family Reveals BnaJAZ8.C03 Involved in the Resistance to Plasmodiophora brassicae in Brassica napus
Authors: Li Lixia , Ji Gaoxiang , Guan Wenjie , Qian Fang , Li Hao , Cai Guangqin , Wu Xiaoming
Published: October 2022

Clubroot caused by Plasmodiophora brassicae led to a significant decrease in the yield and quality of Brassica napus, one of the most important oil crops in the world. JAZ proteins are an essential repressor of jasmonates (JAs) signaling cascades, which have been reported to regulate the resistance to P. brassicae in B. napus. In this study, we identified 51, 25 and 26 JAZ proteins in B. napus, B. rapa and B. oleracea, respectively. Phylogenetic analysis displayed that the notedJAZ proteins were divided into six groups. The JAZ proteins clustered in the same group shared a similar motif composition and distribution order. The 51 BnaJAZs were not evenly assigned on seventeen chromosomes in B. napus, except for A04 and C07. The BnaJAZs of the AtJAZ7/AtJAZ8 group presented themselves to be significantly up-regulated after inoculation by P. brassicae. Variation analysis in a population with a specific resistance performance in P. brassicae displayed a 64 bp translocation in BnaC03T0663300ZS (BnaJAZ8.C03, homologous to AtJAZ8) with an 8% reduction in the disease index on average. Through protein–protein interaction analysis, 65 genes were identified that might be involved in JAZ8 regulation of resistance to P. brassicae in B. napus, which provided new clues for understanding the resistance mechanism to P. brassicae.
Ginsenoside Compound K Ameliorates Development of Diabetic Kidney Disease through Inhibiting TLR4 Activation Induced by Microbially Produced Imidazole Propionate
Authors: Chen Qian , Ren Dongwen , Liu Luokun , Xu Jingge , Wu Yuzheng , Yu Haiyang , Liu Mengyang , Zhang Yi , Wang Tao
Published: October 2022

Diabetic kidney disease (DKD) is a common and devastating complication in diabetic patients, which is recognized as a large and growing problem leading to end-stage kidney disease. As dietary-mediated therapies are gradually becoming more acceptable to patients with DKD, we planned to find active compounds on preventing DKD progression from dietary material. The present paper reports the renoprotective properties and underlying mechanisms of ginsenoside compound K (CK), a major metabolite in serum after oral administration of ginseng. CK supplementation for 16 weeks could improve urine microalbumin, the ratio of urinary albumin/creatinine and renal morphological abnormal changes in db/db mice. In addition, CK supplementation reshaped the gut microbiota by decreasing the contents of Bacteroides and Paraprevotella and increasing the contents of Lactobacillu and Akkermansia at the genus level, as well as reduced histidine-derived microbial metabolite imidazole propionate (IMP) in the serum. We first found that IMP played a significant role in the progression of DKD through activating toll-like receptor 4 (TLR4). We also confirmed CK supplementation can down-regulate IMP-induced protein expression of the TLR4 signaling pathway in vivo and in vitro. This study suggests that dietary CK could offer a better health benefit in the early intervention of DKD. From a nutrition perspective, CK or dietary material containing CK can possibly be developed as new adjuvant therapy products for DKD.
Effects of Sarcoptes scabiei Translationally Controlled Tumor Protein (TCTP) on Histamine Release and Degranulation of KU812 Cells
Authors: Xu Ziyi , Xu Yanting , Gu Xiaobin , Xie Yue , He Ran , Xu Jing , Jing Bo , Peng Xuerong , Yang Guangyou
Published: October 2022

Scabies is a common parasitic dermatological infection worldwide that is often neglected. Scabies mites stimulate host inflammatory symptoms via secreted and excreted proteins, which induce basophil and mast cell degranulation and host histamine release. However, the mechanism of degranulation and histamine release is unclear. Moreover, the Sarcoptes scabiei translationally controlled tumor protein (TCTP) is predicted as an excreted protein, which may be involved in host inflammatory response regulation. First, we evaluated S. scabiei TCTP gene (SsTCTP) transcription in larvae, nymphs, and adults by qRT-PCR, and SsTCTP transcription was highest in larvae, followed by nymphs. Second, we found that the S. scabiei TCTP recombinant protein (rSsTCTP) promoted mice histamine release in vivo by Evans blue Miles assay. Therefore, to further explore the possible role of S. scabiei TCTP in host inflammatory response regulation, we established a degranulation model of KU812 cells. The results of the degranulation model suggested that rSsTCTP could induce enhanced degranulation of KU812 cells and increase the secretion of histamine and the expression of IL-4, IL-6, and IL-13 in vitro. In conclusion, we speculate that scabies mites could stimulate host histamine release and Th2 response by excreting S. scabiei TCTP.
Dissecting the Many Faces of Frontotemporal Dementia: An Imaging Perspective
Authors: Pengo Marta , Premi Enrico , Borroni Barbara
Published: October 2022

Frontotemporal dementia (FTD) is a heterogeneous clinical and neuropathological disorder characterized by behavioral abnormalities, executive dysfunctions and language deficits. FTD encompasses a wide range of different pathological entities, associated with the accumulation of proteins, such as tau and TPD-43. A family history of dementia is found in one third of cases, and several genes causing autosomal dominant inherited disease have been identified. The clinical symptoms are preceded by a prodromal phase, which has been mainly studied in cases carrying pathogenetic mutations. New experimental strategies are emerging, in both prodromal and clinical settings, and outcome markers are needed to test their efficacy. In this complex context, in the last few years, advanced neuroimaging techniques have allowed a better characterization of FTD, supporting clinical diagnosis, improving the comprehension of genetic heterogeneity and the earliest stages of the disease, contributing to a more detailed classification of underlying proteinopathies, and developing new outcome markers on clinical grounds. In this review, we briefly discuss the contribution of brain imaging and the most recent techniques in deciphering the different aspects of FTD.
CircTCF4 Suppresses Proliferation and Differentiation of Goat Skeletal Muscle Satellite Cells Independent from AGO2 Binding
Authors: Zheng Shuailong , Li Li , Zhou Helin , Zhang Xujia , Xu Xiaoli , Dai Dinghui , Zhan Siyuan , Cao Jiaxue , Guo Jiazhong , Zhong Tao , Wang Linjie , Zhang Hongping
Published: October 2022

The proliferation and differentiation of mammalian skeletal muscle satellite cells (MuSCs) are highly complicated. Apart from the regulatory signaling cascade driven by the protein-coding genes, non-coding RNAs such as microRNAs (miRNA) and circular RNAs (circRNAs) play essential roles in this biological process. However, circRNA functions in MuSCs proliferation and differentiation remain largely to be elucidated. Here, we screened for an exonic circTCF4 based on our previous RNA-Seq data, specifically expressed during the development of the longest dorsal muscle in goats. Subsequently, the circular structure and whole sequence of circTCF4 were verified using Sanger sequencing. Besides, circTCF4 was spatiotemporally expressed in multiple tissues from goats but strikingly enriched in muscles. Furthermore, circTCF4 suppressed MuSCs proliferation and differentiation, independent of AGO2 binding. Finally, we conducted Poly(A) RNA-Seq using cells treated with small interfering RNA targeting circTCF4 and found that circTCF4 would affect multiple signaling pathways, including the insulin signaling pathway and AMPK signaling pathway related to muscle differentiation. Our results provide additional solid evidence for circRNA regulating skeletal muscle formation.
Activation of Piezo1 Increases Na,K-ATPase-Mediated Ion Transport in Mouse Lens
Authors: Shahidullah Mohammad , Rosales Joaquin Lopez , Delamere Nicholas
Published: October 2022

Lens ion homeostasis depends on Na,K-ATPase and NKCC1. TRPV4 and TRPV1 channels, which are mechanosensitive, play important roles in mechanisms that regulate the activity of these transporters. Here, we examined another mechanosensitive channel, piezo1, which is also expressed in the lens. The purpose of the study was to examine piezo1 function. Recognizing that activation of TRPV4 and TRPV1 causes changes in lens ion transport mechanisms, we carried out studies to determine whether piezo1 activation changes either Na,K-ATPase-mediated or NKCC1-mediated ion transport. We also examined channel function of piezo1 by measuring calcium entry. Rb uptake was measured as an index of inwardly directed potassium transport by intact mouse lenses. Intracellular calcium concentration was measured in Fura-2 loaded cells by a ratiometric imaging technique. Piezo1 immunolocalization was most evident in the lens epithelium. Potassium (Rb) uptake was increased in intact lenses as well as in cultured lens epithelium exposed to Yoda1, a piezo1 agonist. The majority of Rb uptake is Na,K-ATPase-dependent, although there also is a significant NKCC-dependent component. In the presence of ouabain, an Na,K-ATPase inhibitor, Yoda1 did not increase Rb uptake. In contrast, Yoda1 increased Rb uptake to a similar degree in the presence or absence of 1 µM bumetanide, an NKCC inhibitor. The Rb uptake response to Yoda1 was inhibited by the selective piezo1 antagonist GsMTx4, and also by the nonselective antagonists ruthenium red and gadolinium. In parallel studies, Yoda1 was observed to increase cytoplasmic calcium concentration in cells loaded with Fura-2. The calcium response to Yoda1 was abolished by gadolinium or ruthenium red. The calcium and Rb uptake responses to Yoda1 were absent in calcium-free bathing solution, consistent with calcium entry when piezo1 is activated. Taken together, these findings point to stimulation of Na,K-ATPase, but not NKCC, when piezo1 is activated. Na,K-ATPase is the principal mechanism responsible for ion and water homeostasis in the lens. The functional role of lens piezo1 is a topic for further study.