Miracle-dz/UniFAR-FTUs huggingface dataset:
Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice

Significance Psychedelic compounds, such as psilocybin, have beneficial actions in several psychiatric diseases. They also produce strong alterations of consciousness, which may be a barrier to their widespread use. We found that psilocybin has fast-acting antidepressant-like properties in mice. Using multiple assays of hedonic behavior and an antagonist of prohallucinatory 5-HT2A receptors, we further suggest that altered perception may not be necessary for its therapeutic actions. We also showed that psilocybin strengthens connections between brain cells in regions important for processing rewards and emotions. These experiments suggest that it may be possible to retain the beneficial actions of psilocybin while minimizing the alterations in consciousness, thereby accelerating its use in the clinic. Depression is a widespread and devastating mental illness and the search for rapid-acting antidepressants remains critical. There is now exciting evidence that the psychedelic compound psilocybin produces not only powerful alterations of consciousness, but also rapid and persistent antidepressant effects. How psilocybin exerts its therapeutic actions is not known, but it is widely presumed that these actions require altered consciousness, which is known to be dependent on serotonin 2A receptor (5-HT2AR) activation. This hypothesis has never been tested, however. We therefore asked whether psilocybin would exert antidepressant-like responses in mice and, if so, whether these responses required 5-HT2AR activation. Using chronically stressed male mice, we observed that a single injection of psilocybin reversed anhedonic responses assessed with the sucrose preference and female urine preference tests. The antianhedonic response to psilocybin was accompanied by a strengthening of excitatory synapses in the hippocampus—a characteristic of traditional and fast-acting antidepressants. Neither behavioral nor electrophysiological responses to psilocybin were prevented by pretreatment with the 5-HT2A/2C antagonist ketanserin, despite positive evidence of ketanserin’s efficacy. We conclude that psilocybin’s mechanism of antidepressant action can be studied in animal models and suggest that altered perception may not be required for its antidepressant effects. We further suggest that a 5-HT2AR–independent restoration of synaptic strength in cortico-mesolimbic reward circuits may contribute to its antidepressant action. The possibility of combining psychedelic compounds and a 5-HT2AR antagonist offers a potential means to increase their acceptance and clinical utility and should be studied in human depression.
The Evolution and Distribution of Pneumococcal Serotypes in Adults Hospitalized With Community-Acquired Pneumonia in Spain Using a Serotype-Specific Urinary Antigen Detection Test: The CAPA Study, 2011–2018

Abstract Background Spain introduced the 13-valent pneumococcal conjugate vaccine (PCV13) in the childhood National Immunization Program in 2015–2016 with coverage of 3 doses of 94.8% in 2018. We assessed the evolution of all pneumococcal, PCV13 vaccine type (VT), and experimental PCV20-VT (PCV13 + serotypes 8, 10A, 11A, 12F, 15B, 22F, 33F) hospitalized community-acquired pneumonia (CAP) in adults in Spain from 2011–2018. Methods A prospective observational study of immunocompetent adults (≥18 years) admitted to 4 Spanish hospitals with chest X-ray–confirmed CAP between November 2011 and November 2018. Microbiological confirmation was obtained using the Pfizer serotype-specific urinary antigen detection tests (UAD1/UAD2), BinaxNow test for urine, and conventional cultures of blood, pleural fluid, and high-quality sputum. Results Of 3107 adults hospitalized with CAP, 1943 were ≥65 years. Underlying conditions were present in 87% (n = 2704) of the participants. Among all patients, 895 (28.8%) had pneumococcal CAP and 439 (14.1%) had PCV13-VT CAP, decreasing from 17.9% (n = 77) to 13.2% (n = 68) from 2011–2012 to 2017–2018 (P = .049). PCV20-VT CAP occurred in 243 (23.8%) of those included in 2016–2018. The most identified serotypes were 3 and 8. Serotype 3 accounted for 6.9% (n = 215) of CAP cases, remaining stable during the study period, and was associated with disease severity. Conclusions PCV13-VT caused a substantial proportion of CAP in Spanish immunocompetent adults 8 years after introduction of childhood PCV13 immunization. Improving direct PCV13 coverage of targeted adult populations could further reduce PCV13-VT burden, a benefit that could be increased further if PCV20 is licensed and implemented.
Analysis of Cancer Patient Decision-Making and Health Service Utilization after Enforcement of the Life-Sustaining Treatment Decision-Making Act in Korea

Purpose This study aimed to confirm the decision-making patterns for life-sustaining treatment (LST) and analyze medical service utilization changes after enforcement of the Life-Sustaining Treatment Decision-Making Act. Materials and Methods Of 1,237 patients who completed legal forms for life-sustaining treatment (hereafter called the LST form) at three academic hospitals and died at the same institutions, 1,018 cancer patients were included. Medical service utilization and costs were analyzed using claims data. Results The median time to death from completion of the LST form was three days (range, 0 to 248 days). Of these, 517 people died within two days of completing the document, and 36.1% of all patients prepared the LST form themselves. The frequency of use of the intensive care unit, continuous renal replacement therapy, and mechanical ventilation was significantly higher when the families filled out the form without knowing the patient’s intention. In the top 10% of the medical expense groups, the decision-makers for LST were family members rather than patients (28% patients vs. 32% family members who knew and 40% family members who did not know the patient’s intention). Conclusion The cancer patient’s own decision-making rather than the family’s decision was associated with earlier decision-making, less use of some critical treatments (except chemotherapy) and expensive evaluations, and a trend toward lower medical costs.
Changes in the age-specific body mass index distribution among urban children between 2002 and 2018 in Changsha, China

Background It had been reported that the increase in the prevalence of childhood overweight and obesity in several developed countries over the decade was largely a consequence of changes in the upper end of the body mass index (BMI) distribution. We speculated that the change in BMI distribution among Chinese children is different from that in developed countries. Therefore, we investigated the changes in the BMI distribution among urban children in Changsha, China. Methods A secondary data analysis of the 2002 and 2018 Annual Survey on Students’ Constitution and Health from Yuhua District, Changsha City, China was performed. The BMI distribution of children aged 6–15 years (n=72,061) was examined by calculating the BMI value at 5th, 50th, 85th, and 95th percentiles. Differences in the BMI value at the 5th, 50th, 85th, and 95th percentiles between 2002 and 2018 according to age and sex were calculated. Results From 2002 to 2018, the standardized rate of underweight decreased from 6.9% to 3.4%, whereas that of obesity increased from 6.1% to 13.8%. The BMI of the population increased over the 16-year period. The greatest change between the years was seen in the 85th percentile, and moderate changes were seen in the 5th and 50th BMI percentiles. Also, the greatest changes in the BMI percentiles were evident at age 12–14 years. Conclusions The whole spectrum of BMI distribution among school-aged children shifted over the 16-year study period, although the increases were more marked in the upper than lower percentiles. Health professionals and health policymakers should develop strategies and interventions aimed at preventing adverse health effects caused by this change.
Low risk of SARS-CoV-2 in blood transfusion

Background The novel coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), continues to remain a global challenge. There is emerging evidence of SARS-CoV-2 virus found in the blood of patients from China and some developed countries. However, there is inadequate data reported in Ghana and other parts of Africa, where blood transfusion service heavily relies on voluntary and replacement blood donors. This study aimed to investigate whether plasma of infected individuals could pose significant transfusion transmitted risk of COVID-19 in Ghanaian populations. Methods This cross-sectional retrospective study was conducted at the Kumasi Centre for Collaborative Research into Tropical Medicine (KCCR), KNUST, Ghana. Study subjects comprised contacts of COVID-19 individuals, those with classical symptoms of COVID-19 and individuals who had recovered based on the new Ghana discharge criteria. Whole blood, sputum or deep coughed saliva samples were collected and transported to KCCR for SARS-CoV-2 testing. Viral nucleic acid was extracted from sputum/nasopharyngeal samples using Da An Gene column based kit and from plasma using LBP nucleic acid extraction kit. Real-Time PCR was performed specifically targeting the ORF1ab and Nucleocapsid (N) genomic regions of the virus. Results A total of 97 individuals were recruited into the study, with more than half being males (58; 59.7%). The mean age of all subjects was 33 years (SD = 7.7) with minimum being 22 years and maximum 56 years. Majority (76; 78.4%) of all the subjects were asymptomatic, and among the few symptomatic subjects, cough (10; 10.3%) was the most predominant symptom. Of the 97 sputum samples tested, 79 (81.4%) were positive for SARS-CoV-2. We identified SARS-CoV-2 viral RNA in the plasma of 1 (1.03%) subject who had clinically recovered. Conclusion This study reports the identification of SARS-CoV-2 viral RNA in a convalescent individual in Ghana. Due to the low prevalence observed and the marginal cycling thresholds associated, the risk of transfusion transmission of SARS-CoV-2 is negligible. Well-powered studies and advanced diagnostics to determine infectious viremia is recommended to further evaluate the potential risk of hematogenous transmission among recovered patients.
Efficacy and breadth of adjuvanted SARS-CoV-2 receptor-binding domain nanoparticle vaccine in macaques

Significance The emergence of SARS-CoV-2 variants of concern (VOCs) that reduce the efficacy of current COVID-19 vaccines is a major threat to pandemic control. We evaluate a SARS-CoV-2 spike receptor-binding domain ferritin nanoparticle protein vaccine (RFN) in a nonhuman primate challenge model that addresses the need for a next-generation vaccine with increased pan-SARS breadth of coverage. RFN, adjuvanted with a liposomal-QS21 formulation (ALFQ), elicits humoral and cellular immune responses with excellent breadth and potency against SARS-CoV-2 VOCs and SARS-CoV-1, and protects against high-dose respiratory tract challenge with SARS-CoV-2. Our results support consideration of RFN for vaccine development against multiple concerning members of the Sarbecovirus subgenus of Betacoronaviruses. Emergence of novel variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need for next-generation vaccines able to elicit broad and durable immunity. Here we report the evaluation of a ferritin nanoparticle vaccine displaying the receptor-binding domain of the SARS-CoV-2 spike protein (RFN) adjuvanted with Army Liposomal Formulation QS-21 (ALFQ). RFN vaccination of macaques using a two-dose regimen resulted in robust, predominantly Th1 CD4+ T cell responses and reciprocal peak mean serum neutralizing antibody titers of 14,000 to 21,000. Rapid control of viral replication was achieved in the upper and lower airways of animals after high-dose SARS-CoV-2 respiratory challenge, with undetectable replication within 4 d in seven of eight animals receiving 50 µg of RFN. Cross-neutralization activity against SARS-CoV-2 variant B.1. 351 decreased only approximately twofold relative to WA1/2020. In addition, neutralizing, effector antibody and cellular responses targeted the heterotypic SARS-CoV-1, highlighting the broad immunogenicity of RFN-ALFQ for SARS-CoV−like Sarbecovirus vaccine development.
RELATIONSHIP BETWEEN PATHOLOGICAL MENSTRUAL SYMPTOMS AND THE DEVELOPMENT OF EXTRAGENITAL FORMS OF LOCAL INFLAMMATION.

OBJECTIVE The aim: To evaluate the parameters of menstrual function in 1015 women of reproductive age and to establish the relationship between the detected menstrual disorders and the development of migraine and/or irritable bowel syndrome (IBS). PATIENTS AND METHODS Materials and methods: During 2018-2020, a survey of women of reproductive age in the Ternopil region (Ukraine) was conducted. To interview the study respondents, we developed a questionnaire that assessed the parameters of menstrual function (age of menarche; regularity and cyclicity of menstrual changes; duration of the menstrual cycle and menstruation itself; the amount of blood loss with the pictogram, the presence of clots and their size) identify characteristic changes in health, symptoms of irritable bowel syndrome and migraine associated with the menstrual cycle. Data analysis was performed by statistical and mathematical method. RESULTS Results and conclusions: In 72.2 % of respondents, the study revealed deviations from the normal course of the menstrual cycle. In particular, an increase in blood loss during menstruation and the appearance of clots larger than 1 cm were observed in 40.8 % of women. Among patients with menstrual dysfunction, 51.8 % of patients had symptoms of irritable bowel syndrome, and 44.1 % had signs of migraine. Thus, the relationship between cyclic menstrual disorders and the formation of IBS and migraine, which significantly affects the deterioration of health, performance of women of childbearing age.
Value of circulating tumor cells in the diagnosis and treatment of solitary pulmonary nodules

Background Lung cancer has become the most common malignant tumor worldwide, with the highest rates of morbidity and mortality. The detection of circulating tumor cells (CTCs) can be simple, rapid, and minimally invasive, thus endowing them with a high value in the diagnosis of malignant tumors. We aimed to explore the correlation between CTCs in peripheral blood and benign or malignant solitary pulmonary nodules (SPNs). Methods A total of 223 patients with SPNs from January 2018 to May 2020 were recruited. During the same period, 20 healthy volunteers were recruited as controls. Venous blood samples were collected from participants for detecting CTCs using a folate receptor (FR)-positive cell detection kit, as well as tumor biomarkers. Results A significant difference in the level of CTCs were observed between the malignant SPNs group, the benign SPNs group, and the control group, which was markedly higher in the malignant SPNs group (10.48±3.49 FU/3 mL) than both the benign SPNs and control groups (6.38±0.53 and 4.45±1.21 FU/3 mL, respectively) (P<0.001). In addition, the level of CTCs was significantly higher in the benign SPNs group than in the control group (P=0.023). In particular, in the malignant SPNs group, patients older than 60 years (11.45±3.92 FU/3 mL) presented a notably higher level of CTCs than other patients (9.55±2.74 FU/3 mL). The patients were then classified according to the pathological subtypes of lung cancer. There was a significant difference in level of CTCs among patients with squamous cell carcinoma (9.10±1.94 FU/3 mL), adenocarcinoma (10.77±3.71 FU/3 mL), and adenosquamous cell carcinoma (11.78±2.61 FU/3 mL). Binary logistic regression analysis suggested that CTCs were an independent risk factor of malignant SPN (OR =3.698, 95% CI: 1.136–11.035, P=0.030). The sensitivity and specificity of CTCs in diagnosing malignant SPNs was significantly higher than tumor biomarkers (single or combined) [sensitivity =89.1%; specificity =92.3%; area under curve (AUC) (95% CI) =0.907 (0.861–0.942)]. Conclusions Peripheral blood CTCs can be used in the diagnosis of malignant SPNs and are recommended for clinical application.
Global RNA profiles show target selectivity and physiological effects of peptide-delivered antisense antibiotics

Abstract Antisense peptide nucleic acids (PNAs) inhibiting mRNAs of essential genes provide a straight-forward way to repurpose our knowledge of bacterial regulatory RNAs for development of programmable species-specific antibiotics. While there is ample proof of PNA efficacy, their target selectivity and impact on bacterial physiology are poorly understood. Moreover, while antibacterial PNAs are typically designed to block mRNA translation, effects on target mRNA levels are not well-investigated. Here, we pioneer the use of global RNA-seq analysis to decipher PNA activity in a transcriptome-wide manner. We find that PNA-based antisense oligomer conjugates robustly decrease mRNA levels of the widely-used target gene, acpP, in Salmonella enterica, with limited off-target effects. Systematic analysis of several different PNA-carrier peptides attached not only shows different bactericidal efficiency, but also activation of stress pathways. In particular, KFF-, RXR- and Tat-PNA conjugates especially induce the PhoP/Q response, whereas the latter two additionally trigger several distinct pathways. We show that constitutive activation of the PhoP/Q response can lead to Tat-PNA resistance, illustrating the utility of RNA-seq for understanding PNA antibacterial activity. In sum, our study establishes an experimental framework for the design and assessment of PNA antimicrobials in the long-term quest to use these for precision editing of microbiota.
Pediatric Thoracolumbar Spinal Injuries in United States Trauma Centers

Objectives Injuries are the leading cause of morbidity and mortality in children ages 1 to 18 years. There are limited studies about pediatric thoracolumbar (TL) spinal injuries; the purpose of this study was to characterize TL spinal injuries among pediatric patients evaluated in US trauma centers. Methods This was a retrospective cohort study of the National Trauma Data Bank. Patients aged 1 to 18 years with a thoracic or lumbar spinal injury sustained by blunt trauma during calendar years 2011 through 2016 were included. Cervical spinal injuries, death before arrival, or penetrating trauma were excluded. The data was abstracted, and missing data was addressed by imputations. Data was analyzed using descriptive statistics and multinomial logistic regressions. Results A total of 20,062 patients were included in the study. Thoracolumbar spinal injuries were more commonly sustained by 16- to 17-year-olds (45.7%), boys (56.6%), and White (74.8%). The injuries were often from a motor vehicle collision (MVC) (55.2%) and resulted in a bone injury (82.3%). Mechanism of injury and age were significant in predicting injury type. A fall was more likely than MVC to result in disc injury (odds ratio [OR], 1.70; 95% confidence interval [CI], 1.24–2.33), strain injury (OR, 1.18; 95% CI, 1.05–1.34), or cord injury (OR, 1.27; 95% CI, 1.12–1.45). Younger children were more likely than adolescents to present with disc injury (OR, 2.79; 95% CI, 1.75–4.45), cord injury (OR, 1.46; 95% CI, 1.18–1.81), or strain injury (OR, 1.37; 95% CI, 1.09–1.72). Conclusions To our knowledge, this is the largest pediatric TL spinal study. Clinicians should consider TL spinal injuries when adolescents present after an MVC, and specifically, TL spinal cord injuries when young children present after a fall. Additionally, pediatric TL spinal injury prevention should highlight motor vehicle and fall safety.
Correlation between small intestinal bacterial overgrowth and irritable bowel syndrome and the prognosis of treatment.

BACKGROUND The aim of the present study was to analyze the relationship between small intestinal bacterial overgrowth (SIBO) and irritable bowel syndrome (IBS) and the prognosis of treatment. METHODS A total of127 IBS patients (IBS group) were selected, and based on the results of the methane/hydrogen breath test, they were divided into SIBO-positive group (subdivided into the antibiotic group, microecological group, and placebo group according to difference in treatment methods) and the SIBO-negative group. The incidence of SIBO and inflammatory factors in different populations were compared. Moreover, differences in the negative conversion rate of intestinal bacterial overgrowth, symptom improvement, interleukin (IL)-1β, and IL-10 levels in the antibiotic group, microecological group, and placebo group before and after treatment were compared. RESULTS The IL-1β level of the IBS group was higher than that of the control group, but the level of IL-10 was lower than that of the control group (P<0.05). The level of IL-1β in the SIBO-positive group was higher than that in the SIBO-negative group, while IL-10 level was lower in the SIBO-positive group compared with the SIBO-negative group (P<0.05). Symptom scores after treatment in the antibiotic group and the microecological group were lower than those in the same groups before treatment and those in the placebo group after treatment (P<0.05). After treatment, the level of IL-1β in the antibiotic group and the microecological group decreased, whereas the level of IL-10 increased (P<0.05). Furthermore, the total clinical effective rate and negative conversion rate of the antibiotic group and the microecological group were higher than those of the placebo group (P<0.05); however, the comparison of symptom scores, inflammatory factors, and total clinical effective rate before and after treatment in the placebo group was not statistically significant (P<0.05). The symptom score after treatment in the negative conversion group was lower than that in the non-negative conversion group (P<0.05). CONCLUSIONS SIBO plays an important role in the occurrence of IBS. Antibiotics and microecological agents can be used to correct SIBO in clinical practice to improve the symptoms of IBS patients and peripheral blood inflammatory factors.
MicroRNA-30 regulates left ventricular hypertrophy in chronic kidney disease

Left ventricular hypertrophy (LVH) is a primary feature of cardiovascular complications in patients with chronic kidney disease (CKD). miRNA-30 is an important posttranscriptional regulator of LVH, but it is unknown whether miRNA-30 participates in the process of CKD-induced LVH. In the present study, we found that CKD not only resulted in LVH but also suppressed miRNA-30 expression in the myocardium. Rescue of cardiomyocyte-specific miRNA-30 attenuated LVH in CKD rats without altering CKD progression. Importantly, in vivo and in vitro knockdown of miRNA-30 in cardiomyocytes led to cardiomyocyte hypertrophy by upregulating the calcineurin signaling directly. Furthermore, CKD-related detrimental factors, such as fibroblast growth factor-23, uremic toxin, angiotensin II, and transforming growth factor–β, suppressed cardiac miRNA-30 expression, while miRNA-30 supplementation blunted cardiomyocyte hypertrophy induced by such factors. These results uncover a potentially novel mechanism of CKD-induced LVH and provide a potential therapeutic target for CKD patients with LVH.