bluuebunny/crossref_metadata_2025_split huggingface dataset:
A pilot study of cerebral metabolism and serotonin 5-HT2A receptor occupancy in rats treated with the psychedelic tryptamine DMT in conjunction with the MAO inhibitor harmine
Authors: Egger Klemens , Gudmundsen Frederik , Jessen Naja Støckel , Baun Christina , Poetzsch Sandra N. , Shalgunov Vladimir , Herth Matthias M. , Quednow Boris B. , Martin-Soelch Chantal , Dornbierer Dario , Scheidegger Milan , Cumming Paul , Palner Mikael 
Published: October 2023

Rationale: The psychedelic effects of the traditional Amazonian botanical decoction known as ayahuasca are often attributed to agonism at brain serotonin 5-HT2A receptors by N,N-dimethyltryptamine (DMT). To reduce first pass metabolism of oral DMT, ayahuasca preparations additionally contain reversible monoamine oxidase A (MAO-A) inhibitors, namely β-carboline alkaloids such as harmine. However, there is lacking biochemical evidence to substantiate this pharmacokinetic potentiation of DMT in brain via systemic MAO-A inhibition.Objectives: We measured the pharmacokinetic profile of harmine and/or DMT in rat brain, and tested for pharmacodynamic effects on brain glucose metabolism and DMT occupancy at brain serotonin 5-HT2A receptors.Methods: We first measured brain concentrations of harmine and DMT after treatment with harmine and/or DMT at low sub-cutaneous doses (1 mg/kg each) or harmine plus DMT at moderate doses (3 mg/kg each). In the same groups of rats, we also measured ex vivo the effects of these treatments on the availability of serotonin 5-HT2A receptors in frontal cortex. Finally, we explored effects of DMT and/or harmine (1 mg/kg each) on brain glucose metabolism with [18F]FDG-PET.Results: Results confirmed that co-administration of harmine inhibited the formation of the DMT metabolite indole-3-acetic acid (3-IAA) in brain, while correspondingly increasing the cerebral availability of DMT. However, we were unable to detect any significant occupancy by DMT at 5-HT2A receptors measured ex vivo, despite brain DMT concentrations as high as 11.3 µM. We did not observe significant effects of low dose DMT and/or harmine on cerebral [18F]FDG-PET uptake.Conclusion: These preliminary results call for further experiments to establish the dose-dependent effects of harmine/DMT on serotonin receptor occupancy and cerebral metabolism.
Anti-inflammatory and antioxidant activity of ursolic acid: a systematic review and meta-analysis
Authors: Zhao Man , Wu Fengyang , Tang Zhaohong , Yang Xinyu , Liu Yanhua , Wang Fengxia , Chen Baojiang 
Published: October 2023

Introduction: There is currently evidence suggesting that ursolic acid may exert a favorable influence on both anti-inflammatory and antioxidant impact. Nevertheless, the anti-inflammatory and antioxidant activities of ursolic acid have not been systematically evaluated. Consequently, this study aims to conduct a systematic review and meta-analysis regarding the impact of ursolic acid on markers of inflammatory and antioxidant activity in both animal models and in vitro systems.Methods: The search encompassed databases such as PubMed, Web of Science, Google Scholar, and ScienceDirect, up until May 2023. All eligible articles in English were included in the analysis. Standard mean difference (SMD) was pooled using a random-effects model, and the included studies underwent a thorough assessment for potential bias.Results: The final review comprised 31 articles. In disease-model related studies, animal experiments have consistently shown that ursolic acid significantly reduced the levels of inflammatory parameters IL-1β, IL-6 and TNF-α in mouse tissues. In vitro studies have similarly showed that ursolic acid significantly reduced the levels of inflammatory parameters IL-1β, IL-6, IL-8 and TNF-α. Our results showed that ursolic acid could significantly elevate SOD and GSH levels, while significantly reducing MDA levels in animal tissues. The results of in vitro studies shown that ursolic acid significantly increased the level of GSH and decreased the level of MDA.Discussion: Findings from both animal and in vitro studies suggest that ursolic acid decreases inflammatory cytokine levels, elevates antioxidant enzyme levels, and reduces oxidative stress levels (graphical abstract). This meta-analysis furnishes compelling evidence for the anti-inflammatory and antioxidant properties of ursolic acid.
Efficacy and safety of Ophiocordyceps sinensis in the treatment of Hashimoto’s thyroiditis: a systematic review and meta-analysis
Authors: Wei Maoying , Ma Wenxin , Zhang Wenhua , Yin Dan , Tang Yiting , Jia Weiyu , Jiang Yijia , Wang Churan , Gong Yanbing 
Published: October 2023

Objective: To evaluate the efficacy and safety of Ophiocordyceps sinensis (OS) preparations for the treatment of Hashimoto’s thyroiditis (HT).Methods: We searched eight databases to collect randomized controlled trials (RCTs) of OS combined with a low-iodine diet or levothyroxine for HT. The search period was from inception to June 2023. Meta-analysis was performed using Revman 5.3 software after two evaluators independently screened the literature, extracted data, and evaluated the risk of bias of the included studies. The GRADE system was used to assess the certainty of evidence.Results: A total of 14 RCTs involving 1,014 patients with HT were included. Meta-analysis showed that OS preparations combined with a low-iodine diet were more effective in reducing thyroid peroxidase antibody (TPOAb) [SMD = −3.81, 95% CI (−5.07, −2.54), p &lt; 0.00001] and thyroglobulin antibody (TgAb) [SMD = −4.73, 95% CI (−6.86, −2.61), p &lt; 0.00001] compared to a low-iodine diet. Compared with levothyroxine treatment alone, OS preparations combined with levothyroxine further reduced TPOAb [SMD = −2.04, 95% CI (−2.82, −1.26), p &lt; 0.00001], TgAb [SMD = −2.01, 95% CI (−2.68, −1.33), p &lt; 0.00001], tumor necrosis factor alpha (TNF-α) [SMD = −3.40, 95% CI (−5.66, −1.14), p = 0.003], interleukin-2 (IL-2) [SMD = −2.31, 95% CI (−3.98, −0.65), p = 0.006], and interleukin-6 (IL-6) [MD = −4.16, 95% CI (−6.17, −2.15), p &lt; 0.0001], and elevated free thyroxine (FT4) [SMD = 1.34, 95% CI (0.59, 2.08), p = 0.0004], but no significant effect on free triiodothyronine (FT3) [SMD = 0.83, 95% CI (−0.12, 1.78), p = 0.09] and thyroid stimulating hormone (TSH) [SMD = −0.80, 95% CI (−1.71, 0.11), p = 0.08]. In terms of safety, three studies reported adverse reactions in 10 patients in each of the experimental and control groups.Conclusion: OS preparations in combination with other treatments (low-iodine diet or levothyroxine) may decrease thyroid autoantibodies and inflammatory responses in patients with HT. In HT patients with hypothyroidism, the combination of the OS preparations with levothyroxine also improved FT4. However, the quality of the included studies was generally low. Moreover, the safety of OS preparations remains unclear. Therefore, more high-quality, multicenter, large-sample RCTs are needed in the future to validate the efficacy and safety of OS preparations.Systematic Review Registration:https://www.crd.york.ac.uk/prospero, identifier CRD42023432663
Amphetamines in child medicine: a review of ClinicalTrials.gov
Authors: Alalalmeh Samer O. , Hegazi Omar E. , Shahwan Moyad , Alshehri Fahad S. , Ashour Ahmed M. , Algarni Alanood S. , Alorfi Nasser M. 
Published: October 2023

Background: Globally, the use of amphetamines as therapeutic agents in pediatric medicine is a crucial area of concern, especially given the population’s vulnerability.Methods: On 6 August 2023, a search was conducted on ClinicalTrials.gov using “amphetamine” as the keyword. Two independent examiners screened trials against set criteria, including a focus on amphetamine, completion status, an interventional approach, and included children. Ongoing or observational studies were excluded. Data extracted from the qualified trials encompassed primary objectives, participant counts, study duration, and outcomes, with the aim of analyzing children disorders treated by amphetamine.Results: On 6 August 2023, a search of the ClinicalTrials.gov database with the term “amphetamines” identified 179 clinical trials. After extensive exclusion criteria, 19 trials were ultimately selected for analysis. The predominant condition under investigation was attention deficit hyperactivity disorder (ADHD), present in 84.2% of studies. Key study characteristics included: phase 4 trials (36.8%), randomized allocation (63.2%), and the parallel intervention model (42.1%). Masking techniques varied, with no masking in 42.1% of studies, and double and quadruple masking both accounting for 21.1%. Geographically, 78.9% of the studies’ participants were from the United States.Conclusion: This study highlights the notable therapeutic potential of amphetamines in pediatric ADHD populations and emphasizes the importance of recognizing potential side effects and addiction risks. As pharmacogenomics offers the prospect of personalized treatments, there is potential to increase therapeutic efficacy and decrease adverse reactions. It is vital to balance these benefits against the inherent risks, understanding the need for continued research to optimize the use of amphetamines in medicine.
Function verification of a chlorophyll a/b binding protein gene through a newly established tobacco rattle virus-induced gene silencing system in Kandelia obovata
Authors: Zhang Mingxiong , Rao Yuhui , Chen Xiaofeng , Shi Yunrui , Wei Chonglong , Wang Xianfeng , Wang Lu , Xie Chengjin , Pan Chenglang , Chen Jianming 
Published: October 2023

As an important mangrove species, Kandelia obovata plays an irreplaceable role in the coastal ecosystem. However, due to a lack of genetic technology, there is limited research on its functional genes. As such, establishing an efficient and rapid functional verification system is particularly important. In this study,tobacco rattle virus (TRV) and the phytoene desaturase gene KoPDS were used as the vector and target gene, respectively, to establish a virus-induced gene silencing system (VIGS) in K. obovata. Besides, the system was also used to verify the role of a Chlorophyll a/b binding protein (Cab) gene KoCAB in leaf carbon sequestration of K. obovata.RNA-Seq and qRT-PCR showed that the highest gene-silencing efficiency could reach 90% after 10 days of inoculation and maintain above 80% after 15 days, which was achieved with resuspension buffer at pH 5.8 and Agrobacterium culture at OD600 of 0.4-0.6. Taken together, the TRV-mediated VIGS system established herein is the first genetic analysis tool for mangroves, which may greatly impel functional genomics studies in mangrove plants.
Examining the factor structure and validity of the WHOQOL-AGE among the oldest-old Chinese in Singapore
Authors: Cheng Grand H.-L. , Feng QiuShi , Chong Yap-Seng , Koh Woon-Puay 
Published: October 2023

ObjectivesA short measure of quality of life in old age is essential. The present study examined the factor structure and validity of the 13-item WHOQOL-AGE among the oldest-old.MethodsData came from 1,000 Chinese aged ≥85 years in Singapore. Exploratory and confirmatory factor analyzes were conducted on the WHOQOL-AGE. Regression examined the demographic, social and health correlates of the identified factors.ResultsFactor analyzes suggested a bifactor model of the WHOQOL-AGE, which comprised three specific factors, namely “health,” “environment” and “mastery,” in addition to the general factor (“overall”). Partial scalar invariance (concerning only one item) and scalar invariance were established across gender and education level respectively, generally supporting the measurement invariance of this model. Regression results demonstrated known-groups validity. Health correlates were more predictive of “health” than “environment” and “mastery,” with more basic and instrumental activities of daily living, lower depressive symptomatology and fewer falls positively relating to “health.” Strength of social network and social engagement (social correlates) positively related to “environment” and “mastery” but not “health.”ConclusionThe WHOQOL-AGE exhibits a bifactor structure and known-groups validity among the oldest-old Chinese in Singapore. It seems useful to capture different facets of quality of life in the concerned population.
Does altitude have an effect on stroke mortality and hospitalization risk? A comprehensive evaluation of United States data
Authors: Gerken Jacob , Huber Nathan , Zapata Demi , Barron Ileana G. , Zapata Isain 
Published: October 2023

BackgroundGlobally, stroke is a leading cause of death among people over 50 years of age. In the United States alone, over 150,000 people die due to stroke every year. Environmental factors such as altitude may play a role in these outcomes; however, their effects have not yet been comprehensively explored. The objective of this study is to evaluate the effect of altitude along with other covariates on stroke mortality and hospitalization rates in adults.MethodsThis study utilized altitude, stroke mortality and hospitalization rates; antihypertensive and cholesterol-lowering medication usage; smoking prevalence; and sociodemographic data (MH-SVI) obtained from government databases for 3,141 counties in the United States from 2018 to 2020. Data were analyzed using generalized additive models with and without adjustments for covariates.ResultsUnadjusted models show that altitude has a comparable significant negative effect on mortality rates for Black and white populations. When including all covariates, altitude continues to have a significant protective effect against stroke fatalities in white populations (retaining 26.6 and 53.8% of the effect magnitude for cardiovascular disease (CVD) and stroke mortality, respectively), a non-significant effect in the Black population, and a detrimental effect in Hispanic and Asian Pacific populations for CVD mortality (a 21.6 and 39.1% effect increase, respectively).ConclusionOur findings add to the growing body of evidence that environmental factors add to disparities between racial groups and play a significant role in CVD and stroke mortality. The effect of altitude is comparable in size to that of smoking, medication usage, and social determinants of health.
Bioconcentration of carbamazepine, enalapril, and sildenafil in neotropical fish species
Authors: Rojo Macarena Gisele , Cristos Diego , Carriquiriborde Pedro 
Published: October 2023

Sewage effluents are the main source of entry of Human Pharmaceutical Active Ingredients (HPAIs) to surface water bodies. Carbamazepine (CBZ), psychiatric drug, enalapril (ENA) antihypertensive, and sildenafil (SIL), to treat erectile dysfunction, have been frequently detected in receiving wastewater and in wild fish species from Argentina. This study aimed to assess the bioconcentration of selected HPAIs in native fish species of the Del Plata Basin. In a first trial, the bioconcentration factors of CBZ, ENA, and SIL were obtained by exposing Cnesterodon decemmaculatus, respectively, to 135, 309, and 70 μg/L during 96 h. Then the bioconcentration kinetic of SIL was comparatively assessed in C. decemmaculatus and Piaractus mesopotamicus exposed, respectively, to 44.1 and 16.2 μg/L during a one-week, followed by a four-day depuration phase. HPAIs concentrations in water and tissue were measured by HPLC-MS after 0.22 μm filtration and direct injection or solid-liquid extraction, respectively. Bioconcentration factors obtained empirically (BCFe) for C. decemmaculatus were CBZ = 1.5, SIL = 1.4, and ENA = 0.007. Parameters estimated by the SIL bioconcentration kinetic model for C. decemmaculatus were: uptake rate constant (k1) = 5.5 L/kg d, elimination rate constant during uptake phase (k2u) = 0.00175 d−1, maximum predicted tissue concentration (Ct(max)) = 138588 μg/kg, estimated bioconcentration factor (BCFm) = 3143, lag time between the exposure and the first detection in tissue (tlag) = 0 d, elimination rate constant in the depuration phase (k2d) = 0.49 d−1 and half-life in the tissue (t1/2) = 1.4 d. The model parameters for P. mesopotamicus were k1: 7.3 L/kg d, k2u: 0.0836 d−1, Ct(max): 1423 μg/kg, BCFm: 88, tlag: 3.8 d in the uptake phase and k2d: 0.31 d−1 and t1/2: 2.3 d in the depuration phase. The reached conclusions were: 1) the bioconcentration capacity of CBZ and SIL are similar but around 200 times higher than ENA, 2) the time to reach the bioconcentration equilibrium for SIL is longer than 1 week, then estimated BCFm are between 1 and 3 orders of magnitude higher than BCFe obtained after 96 h exposure, but actual values need to be verified, 3) substantial differences (≈30 fold) were observed in the estimated BCF of SIL among species, indicating the need for further studies toward understanding such diversity to improve HPAIs ecological risk assessment worldwide.
Impact of Previous Conventional Cardiac Surgery on the Clinical Outcomes After Heart Transplantation
Authors: Chen Jeng-Wei , Chou Heng-Wen , Chou Nai-Kuan , Wang Chih-Hsien , Chi Nai-Hsin , Huang Shu-Chien , Yu Hsi-Yu , Chen Yih-Sharng , Hsu Ron-Bin 
Published: October 2023

The impact of the type, purpose, and timing of prior surgery on heart transplantation (HT) remains unclear. This study investigated the influence of conventional cardiac surgery (PCCS) on HT outcomes. This study analyzed HTs performed between 1999 and 2019 at a single institution. Patients were categorized into two groups: those with and without PCCS. Short-term outcomes, including post-transplant complications and mortality rates, were evaluated. Cox proportional and Kaplan–Meier survival analyses were used to identify risk factors for mortality and assess long-term survival, respectively. Of 368 patients, 29% had PCCS. Patients with PCCS had a higher incidence of post-transplant complications. The in-hospital and 1 year mortality rates were higher in the PCCS group. PCCS and cardiopulmonary bypass time were significant risk factors for 1 year mortality (hazard ratios = 2.485 and 1.005, respectively). The long-term survival rates were lower in the PCCS group, particularly in the first year. In sub-analysis, patients with ischemic cardiomyopathy and PCCS had the poorest outcomes. The era of surgery and timing of PCCS in relation to HT did not significantly impact outcomes. In conclusion, PCCS worsen the HT outcomes, especially in patients with ischemic etiology. However, the timing of PCCS and era of HT did not significantly affect this concern.
First Molecular Identification of Calicophoron daubneyi (Dinnik, 1962) and Paramphistomum leydeni (Nasmark, 1937) in Wild Ruminants from Romania
Authors: Morariu Sorin , Sîrbu Cătălin Bogdan , Tóth Adrienn Gréta , Dărăbuș Gheorghe , Oprescu Ion , Mederle Narcisa , Ilie Marius Stelian , Imre Mirela , Sîrbu Beatrice Ana-Maria , Solymosi Norbert , Florea Tiana , Imre Kalman 
Published: October 2023

Rumen flukes are geographically widespread trematodes affecting wild and domestic ruminants. The juvenile forms, which are found in the small intestine, are more pathogenic compared to the adults. Severe diarrhoea and weight loss are the major clinical signs, and the disease might be fatal in severely infested individuals. In the last decade, paramphistomosis has been described as an emerging parasitic disease in Europe. This study aimed to identify the rumen fluke species in wild ruminants from western Romania. Fifty-two pre-stomachs obtained from roe deer (Capreolus capreolus) that were hunted on 14 hunting grounds from Timiș and Arad counties were examined for the presence of paramphistomes. Three (9.09%) out of 33 samples were positive in Timiș County, and one (5.26%) out of 19 samples was positive in Arad County. Subsequent PCR testing revealed that three samples were positive for Calicophoron daubneyi and one for Paramphistomum leydeni. The presence of C. daubneyi and P. leydeni in roe deer has not been previously reported in Romania. Two Paramphistomum species—C. daubneyi and P. leydeni—were revealed as the main species of rumen flukes in roe deer from forests in Romania.
Composition of phospholipids of erythrocyte membranes in newborns from mothers with virus pneumonia caused by SARS-CoV-2 in the third trimester of pregnancy
Authors: Ishutina N. A. , Аndrievskaya I. A. , Dovzhikova I. V. , Dorofienko N. N. 
Published: October 2023

Aim. To study the composition of phospholipids in erythrocyte membranes of newborns from mothers who had viral pneumonia caused by SARS-CoV-2 in the third trimester of pregnancy.Materials and methods. The study included newborns who were born to mothers diagnosed with COVID-19 and community-acquired pneumonia of viral etiology in the third trimester (main group). Of the total number of newborns (n=67), groups of children were formed from mothers with moderate pneumonia (group 1, n=34), and with severe pneumonia (group 2, n=33). The control group consisted of 35 newborns from practically healthy mothers. The quantitative composition of phospholipids in the membranes of erythrocytes of venous blood of the umbilical cord of newborns was determined by the method of two-dimensional thin-layer chromatography according to Kirchner.Results. The study found a statistically significant decrease in the concentration of phosphatidylethanolamine and phosphatidylcholine in erythrocyte membranes in group 1 by 19 and 20%, respectively (p<0.001), in group 2 – by 31 and 29%, respectively (p<0.001); a significant increase in the concentration of lysophosphatidylcholine, sphingomyelin, phosphatidylserine and phosphatidylinositol in group 1 by 43, 8, 15 and 26%, respectively (p<0.001), in group 2 – by 67, 14, 23 and 35%, respectively (p<0.001), compared with their concentration in newborns of the control group.Conclusion. Infection of the mother with SARS-CoV-2 during pregnancy is accompanied by structural disintegration of the erythrocyte membranes of their newborns, manifested by a change in the phospholipid profile in favor of an increase in the fractions of sphingo-, lyso-, inositoland serine phospholipids, which, ultimately, can disrupt the work of the oxygen transport system of the blood, contributing to the development of hypoxia.