Miracle-dz/UniFAR-FTUs huggingface dataset:
Toward therapeutic drug monitoring of citalopram in depression? Insights from a systematic review

Background Within the framework of individualized psychopharmacotherapy, therapeutic drug monitoring (TDM) has gained increasing relevance. In the absence of high-quality evidence, the TDM of citalopram (CIT) and the recommended therapeutic ranges of the plasma concentrations have been proposed by guidelines. However, the correlation between the plasma concentration of CIT and treatment outcomes has not been well established. Therefore, the aim of this systematic review was to evaluate the relationship between plasma CIT concentration and treatment outcomes in depression. Research design and methods PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Chinese databases (CNKI, Wanfang Data and Sinomed) were searched up to August 6, 2022. We included clinical studies evaluating the correlation between the plasma CIT concentration and treatment outcomes in patients with depression receiving CIT treatment. Outcomes measured included efficacy, safety, medication adherence, and cost-related outcomes. A narrative synthesis was performed to summarize findings from individual studies. This study was performed according to the Preferred Reporting Items for Systematic Reviews, Meta-Analysis (PRISMA) and the reporting guideline for Synthesis without meta-analysis (SWiM). Results Eleven studies involving 538 patients were included in total. The reported outcomes were mainly efficacy (n = 11) and safety (n = 3); one study reported the duration of hospitalization, and no study reported medication adherence. Regarding the efficacy outcomes, three studies revealed the plasma CIT concentration-response relationship and proposed a lower limit of 50 or 53 ng/mL, whereas this was not found in the rest of the studies. Regarding adverse drug events (ADEs), one study reported more ADEs in the low-concentration group (<50 ng/mL vs. >50 ng/mL), which is not convincing from the perspective of pharmacokinetics/pharmacodynamics. Regarding the cost-related outcomes, only one study reported that the high CIT concentration group (≥50 ng/mL) contributed to shortening the hospitalization duration, but it did not provide detailed information, including direct medical expenses and multiple potential factors contributing to longer hospital stays. Conclusions A definite correlation between plasma concentration and clinical or cost-related outcomes of CIT cannot be drawn, whereas a tendency toward improved efficacy in patients with plasma concentration above 50 or 53 ng/mL was suggestive from limited evidence.
Transradial access with intra-aortic catheter looping for the treatment of intracranial aneurysms

Purpose The study aimed to investigate the feasibility and effect of transradial access with intra-aortic catheter looping for the treatment of intracranial aneurysms. Materials and methods This retrospective one-center study was performed on patients with intracranial aneurysms which were embolized through transradial access with intra-aortic catheter looping because of the difficulty of transfemoral access or transradial access without intra-aortic catheter looping. The imaging and clinical data were analyzed. Results A total of 11 patients were enrolled, including seven (63.6%) male patients. Most patients were associated with one or two risk factors of atherosclerosis. There were nine aneurysms in the left internal carotid artery system and two aneurysms in the right internal carotid artery system. All 11 patients had complications with different anatomic variations or vascular diseases, which made endovascular operation via the transfemoral artery difficult or a failure. The right transradial artery approach was adopted in all patients, and the success rate of intra-aortic catheter looping was 100%. Embolization of intracranial aneurysms was successfully completed in all patients. No instability of the guide catheter was encountered. No puncture site complications or surgical-related neurological complications occurred. Conclusion Transradial access with intra-aortic catheter looping for embolization of intracranial aneurysms is technically feasible, safe, and efficient as an important supplementary approach to the routine transfemoral access or transradial access without intra-aortic catheter looping.
Effect of adipokine and ghrelin levels on BMD and fracture risk: an updated systematic review and meta-analysis

Context Circulating adipokines and ghrelin affect bone remodeling by regulating the activation and differentiation of osteoblasts and osteoclasts. Although the correlation between adipokines, ghrelin, and bone mineral density (BMD) has been studied over the decades, its correlations are still controversial. Accordingly, an updated meta-analysis with new findings is needed. Objective This study aimed to explore the impact of serum adipokine and ghrelin levels on BMD and osteoporotic fractures through a meta-analysis. Data sources Studies published till October 2020 in Medline, Embase, and the Cochrane Library were reviewed. Study selection We included studies that measured at least one serum adipokine level and BMD or fracture risk in healthy individuals. We excluded studies with one or more of the following: patients less than 18 years old, patients with comorbidities, who had undergone metabolic treatment, obese patients, patients with high physical activities, and a study that did not distinguish sex or menopausal status. Data extraction We extracted the data that include the correlation coefficient between adipokines (leptin, adiponectin, and resistin) and ghrelin and BMD, fracture risk by osteoporotic status from eligible studies. Data synthesis A meta-analysis of the pooled correlations between adipokines and BMD was performed, demonstrating that the correlation between leptin and BMD was prominent in postmenopausal women. In most cases, adiponectin levels were inversely correlated with BMD. A meta-analysis was conducted by pooling the mean differences in adipokine levels according to the osteoporotic status. In postmenopausal women, significantly lower leptin (SMD = -0.88) and higher adiponectin (SMD = 0.94) levels were seen in the osteoporosis group than in the control group. By predicting fracture risk, higher leptin levels were associated with lower fracture risk (HR = 0.68), whereas higher adiponectin levels were associated with an increased fracture risk in men (HR = 1.94) and incident vertebral fracture in postmenopausal women (HR = 1.18). Conclusions Serum adipokines levels can utilize to predict osteoporotic status and fracture risk of patients. Systematic review registration https://www.crd. york.ac. uk/prospero/display_record. php? ID=CRD42021224855, identifier CRD42021224855.
Identification of VIPR2 rare and common variants in the Chinese Han population with schizophrenia

Introduction Schizophrenia is a severe and chronic psychiatric disorder with hereditary risk up to 80% as previous studies indicated. Several researches have demonstrated a significant association between schizophrenia and microduplications that overlap the vasoactive intestinal peptide receptor 2 gene (VIPR2). Methods To further investigate potential causal VIPR2 gene variants, all exons and un-translated portions of the VIPR2 gene were sequenced using amplicon targeted resequencing in 1804 Chinese Han patients with schizophrenia and 996 healthy counterparts in the present study. Results Nineteen rare non-synonymous mutations and 1 frameshift deletion was identified for schizophrenia, among which 5 variants have never been reported so far. Frequencies of rare non-synonymous mutations were significantly different between the two groups. Specifically, the non-synonymous mutation rs78564798 (Pallele = 0.006) as well as two rare variations in the VIPR2 gene’s introns (rs372544903, Pallele = 0.026 and a novel mutation, chr7:159034078, GRCh38, Pallele = 0.048) were significantly associated with schizophrenia. Discussion Our findings add new evidence that the functional and probable causative variants of VIPR2 gene may play an important role in susceptibility to schizophrenia. Further studies on validations of VIPR2’s function in the etiology of schizophrenia are warranted.
Efficacy and safety of Tongmai Jiangtang capsule combined with conventional therapy in the treatment of diabetic peripheral neuropathy: a systematic review and meta-analysis

Background Recently, more and more Chinese patent drugs have been proved to be effective in the treatment of diabetic peripheral neuropathy (DPN). Tongmai Jiangtang capsule (TJC) is one of the representative ones. The present meta-analysis integrated data from several independent studies to determine the efficacy and safety of TJCs combined with routine hypoglycemic therapy for DPN patients, and to evaluate the quality of evidence. Methods SinoMed, Cochrane Library, PubMed, EMBASE, Web of Science, CNKI, Wanfang, VIP databases and registers were searched for randomized controlled trials (RCTs) involving TJC treatment of DPN up to February 18, 2023. Two researchers independently used the Cochrane risk bias tool and comprehensive reporting criteria for Chinese medicine trials to evaluate the methodological quality and reporting quality of the qualified studies. RevMan5.4 was used for Meta-analysis and evidence evaluation, with scores determined for recommendations, evaluation, development and GRADE. The Cochrane Collaboration ROB tool was used to evaluate the quality of the literature. The results of Meta-analysis were represented by forest plots. Results A total of 8 studies were included involving a total sample size of 656 cases. TJCs combined with conventional treatment (CT) could significantly accelerate myoelectricity graphic nerve conduction velocity, including that median nerve motor conduction velocity was faster than those of CT alone [mean difference (MD) = 5.20, 95% confidence interval (CI): 4.31–6.10, P < 0.00001], peroneal nerve motor conduction velocity was faster than those of CT alone (MD = 2.66, 95% CI: 1.63–3.68; P < 0.00001), median nerve sensory conduction velocity was faster than those of CT alone (MD = 3.06, 95% CI: 2.32–3.81, P < 0.00001), and peroneal nerve sensory conduction velocity was faster than those of CT alone (MD = 4.23, 95% CI: 3.30–5.16, P < 0.00001). The total efficiency of the TJCs + CT group was higher than that of the CT group (RR = 1.41, 95% CI: 1.28–1.56, P < 0.00001). The HbA1c after treatment in the TJCs + CT group was lower than that in the CT group (P < 0.05). No adverse drug reactions (ADRs) were reported in the combined TJCs or CT groups. Conclusions TJCs combined with CT reduced the severity of DPN symptoms and no treatment-associated ADRs were reported. However, these results should be considered with caution because there was marked heterogeneity in the research data. Therefore, more stringent RCTs should be designed to validate the efficacy of TJCs in DPN patients. Systematic review registration https://www.crd. york.ac. uk/PROSPERO/display_record. php? RecordID=264522, identifier: CRD42021264522.
Factors associated with euphoria in a large subset of cases using propofol sedation during gastrointestinal endoscopy

Background The utilization of Propofol, a widely used intravenous sedative or anesthetic, is characterized by its quick onset, predictable control, and fleeting half-life during both general anesthesia and intensive care unit sedation. Recent evidence, however, has highlighted propofol’s propensity to induce euphoria, particularly in patients undergoing painless procedures such as gastrointestinal or gastric endoscopy. Given its widespread use in patients undergoing such procedures, this study aims to investigate the clinical evidence and factors that may influence propofol-induced euphoria in these settings. Methods The Addiction Research Center Inventory-Chinese Version (ARCI-CV) scale was administered to 360 patients undergoing gastric or gastrointestinal endoscopy using propofol as a sedative. Patient characteristics including past medical history, depression, anxiety, alcohol abuse, and sleep disturbance were recorded through history taking and assessment using various questionnaires prior to the examination. The euphoric and sedative statuses were assessed at 30 min and 1 week post-examination. Results The experimental results of a survey of 360 patients who underwent gastric or gastrointestinal endoscopy using propofol showed that the mean Morphine–Benzedrine Group (MBG) score before the procedure and after 30 min of the procedure was 4.23 and 8.67, respectively. The mean Pentobarbital–Chlorpromazine–Alcohol Group (PCAG) score before the procedure and after 30 min of the procedure was 3.24 and 6.22, respectively. These results showed that both MBG and PCAG scores increased significantly after the procedure. Certain factors, such as dreaming, propofol dose, duration of anesthesia, and etomidate dose, were all correlated with MBG both at 30 min and 1 week after the examination. In addition, etomidate had an effect of decreasing MBG scores and increasing PCAG scores both at 30 min and 1 week after the examination. Conclusion Taken together, propofol may elicit euphoria and potentially contribute to propofol addiction. There are several risk factors for the development of propofol addiction, including dreaming, propofol dose, duration of anesthesia, and etomidate dose. These findings suggest that propofol may have a euphoric effect and may have the potential for drug addiction and abuse.
The linkages between stomatal physiological traits and rapid expansion of exotic mangrove species (Laguncularia racemosa) in new territories

The fast-growing exotic mangrove species (Laguncularia racemosa) has been widely introduced in new territories such as China to restore mangrove ecosystems. However, the invasiveness, as well as the mechanisms for the rapid expansion after the introduction are still not well studied. Here, we try to reveal possible micro-mechanisms for the fast expansion of L. racemosa, using the data on leaf stomata straits, gas-exchange parameters, stable isotope ratios, carbon-nitrogen allocation from L. racemosa and the adjacent native mangroves (Avicennia marina, Aegiceras corniculatum, Bruguiera gymnorhiza, Kandelia obovata) in Hainan Island, China. We found that the higher density but smaller size stoma of L. racemosa enhanced stomatal conductance and shorten the diffusion path of carbon dioxide, thereby increasing the photosynthetic rate. Moreover, the higher stomatal density of L. racemosa exerts a significant positive effect on transpiration, which thus accelerated the water transport and nutrient uptake to meet the advanced need for nutrients and water for fast-growing. The evidence from leaf δ 13C and carbon-nitrogen allocation further proved that L. racemosa has a lower intrinsic water use efficiency but a higher rate of photosynthesis than native mangrove species. Our results suggest that stomatal morphological and physiological traits could strongly influence the growth of L. racemosa compared to the adjacent native mangroves, which provides a new perspective for the fast expansion of exotic mangrove species in China. These findings also suggest that L. racemosa has an invasive potential in native mangrove habitats, thereby the mangrove reforestation projects by introducing L. racemosa should be treated with caution.
Relationship between human serum albumin and in-hospital mortality in critical care patients with chronic obstructive pulmonary disease

Background The relationship between human serum albumin levels and the prognosis of critical care patients with chronic obstructive pulmonary disease (COPD) remains controversial. Objective To investigate the relationship between serum albumin levels and in-hospital mortality in critical care patients with COPD. METHODS: This study used a retrospective observational cohort from the Medical Information in Intensive Care database (MIMIC-IV) in the United States. Multivariate Cox regression analysis was used to assess the relationship between serum albumin levels and in-hospital mortality. A restricted cubic spline line was also used to explore nonlinear relationship. Results A total of 3,398 critical care patients with COPD were included. The overall in-hospital mortality was 12.4%. We found a negative relationship between human serum albumin and in-hospital mortality (HR = 0.97, 95% CI 0.96–0.99, p = 0.002). Conclusion In critical care patients with COPD, there was a negative association between human serum albumin and in-hospital mortality.
Antipsychotics-induced improvement of cool executive function in individuals living with schizophrenia

Cool executive dysfunction is a crucial feature in people living with schizophrenia which is related to cognition impairment and the severity of the clinical symptoms. Based on electroencephalogram (EEG), our current study explored the change of brain network under the cool executive tasks in individuals living with schizophrenia before and after atypical antipsychotic treatment (before_TR vs. after_TR). 21 patients with schizophrenia and 24 healthy controls completed the cool executive tasks, involving the Tower of Hanoi Task (THT) and Trail-Marking Test A-B (TMT A-B). The results of this study uncovered that the reaction time of the after_TR group was much shorter than that of the before_TR group in the TMT-A and TMT-B. And the after_TR group showed fewer error numbers in the TMT-B than those of the before_TR group. Concerning the functional network, stronger DMN-like linkages were found in the before_TR group compared to the control group. Finally, we adopted a multiple linear regression model based on the change network properties to predict the patient’s PANSS change ratio. Together, the findings deepened our understanding of cool executive function in individuals living with schizophrenia and might provide physiological information to reliably predict the clinical efficacy of schizophrenia after atypical antipsychotic treatment.
TUSK: a ubiquitin hydrolase complex modulating surface protein abundance in trypanosomes

Control of protein levels is vital to cellular homeostasis, for maintaining a steady state, to coordinate changes during differentiation and other roles. In African trypanosomes surface proteins contribute to immune evasion, drug sensitivity and environmental sensing. The trypanosome surface is dominated by the GPI-anchored variant surface glycoprotein, but additional GPI-anchored and trans-membrane domain proteins are present with known roles as nutrient receptors and signal transducers. The evolutionarily conserved deubiquitinase orthologs of Usp7 and Vdu1 in trypanosomes modulate abundance of many surface proteins, including the invariant surface glycoproteins, which have roles in immune evasion and drug sensitivity. Here we identify multiple trypanosome Skp1 paralogs and specifically a divergent paralog SkpZ. Affinity isolation and LCMSMS indicates that SkpZ forms a heterotrimeric complex with TbUsp7 and TbTpr86, a tetratricopeptide-repeat protein. Silencing SkpZ decreases TbUsp7 and TbTpr86 abundance, confirming a direct association. Further, SkpZ knockdown decreases the abundance of multiple trans-membrane domain (TMD) proteins but increases GPI-anchored surface protein levels. Hence, a heterotrimeric complex of TbTpr86, TbUsp7 and SkpZ (TUSK) regulates expression levels of a significant cohort of trypanosome surface proteins mediating coordination between TMD and GPI-anchored protein expression levels.
Tale of two hearts: a TNNT2 hypertrophic cardiomyopathy case report

Hypertrophic cardiomyopathy (HCM) is a heritable cardiomyopathy that is predominantly caused by pathogenic mutations in sarcomeric proteins. Here we report two individuals, a mother and her daughter, both heterozygous carriers of the same HCM-causing mutation in cardiac Troponin T (TNNT2). Despite sharing an identical pathogenic variant, the two individuals had very different manifestations of the disease. While one patient presented with sudden cardiac death, recurrent tachyarrhythmia, and findings of massive left ventricular hypertrophy, the other patient manifested with extensive abnormal myocardial delayed enhancement despite normal ventricular wall thickness and has remained relatively asymptomatic. Recognition of the marked incomplete penetrance and variable expressivity possible in a single TNNT2-positive family has potential to guide HCM patient care.
The complementary role of MRI and FET PET in high grade gliomas to differentiate recurrence from radionecrosis

Background Conventional magnetic resonance imaging (MRI) has limitations in differentiating tumor recurrence (TR) from radionecrosis (RN) in high grade gliomas (HGG), which can present with morphologically similar appearances. Multiparametric advanced MR sequences and Positron Emission Tomography (PET) with amino acid tracers can aid in diagnosing tumor metabolism. The role of both modalities on an individual basis and combined performances were investigated in the current study. Materials and Methods Patients with HGG with MRI and PET within three weeks were included in the retrospective analysis. The multiparametric MRI included T1-contrast, T2-weighted sequences, perfusion, diffusion, and spectroscopy. MRI was interpreted by neuroradiologist without using information from PET imaging. 18F-Fluoroethyl-Tyrosine (FET) uptake was calculated from the areas of maximum enhancement/suspicion, which was assessed by nuclear medicine physician (having access to MRI to determine tumor-to-white matter ratio over a specific region). A definitive diagnosis of TR or RN was made based on the combination of multidisciplinary joint clinic decisions, histopathological examination, and clinic-radiological follow-up as applicable. Results 62 patients were included in the study between July 2018 and August 2021. The histology during initial diagnosis was glioblastoma, oligodendroglioma, and astrocytoma in 43, 7, and 6, respectively, while in 6, no definitive histological characterization was available. The median time from radiation (RT) was 23 months. 46 and 16 patients had TR and RN recurrence, respectively. Sensitivity, specificity, and accuracy using MRI were 98, 77, and 94%, respectively. Using PET imaging with T/W cut-off of 2.65, sensitivity, specificity, and accuracy were 79, 84, 80%, respectively. The best results were obtained using both imaging combined with sensitivity, specificity, and accuracy of 98, 100, and 98%, respectively. Conclusion Combined imaging with MRI and FET-PET offers multiparametric assessment of glioma recurrence that is correlative and complimentary, with higher accuracy and clinical value.