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Schizophrenia is a severe and complex psychiatric disorder that needs treatment based on extensive experience. Antipsychotic drugs have already become the cornerstone of the treatment for schizophrenia; however, the therapeutic effect is of significant variability among patients, and only around a third of patients with schizophrenia show good efficacy. Meanwhile, drug-induced metabolic syndrome and other side-effects significantly affect treatment adherence and prognosis. Therefore, strategies for drug selection are desperately needed. In this study, we will perform pharmacogenomics research and set up an individualised preferred treatment prediction model.
We aim to create a standard clinical cohort, with multidimensional index assessment of antipsychotic treatment for patients with schizophrenia.
This trial is designed as a randomised clinical trial comparing treatment with different kinds of antipsychotics. A total sample of 2000 patients with schizophrenia will be recruited from in-patient units from five clinical research centres. Using a computer-generated program, the participants will be randomly assigned to four treatment groups: aripiprazole, olanzapine, quetiapine and risperidone. The primary outcomes will be measured as changes in the Positive and Negative Syndrome Scale of schizophrenia, which reflects the efficacy. Secondary outcomes include the measure of side-effects, such as metabolic syndromes. The efficacy evaluation and side-effects assessment will be performed at baseline, 2 weeks, 6 weeks and 3 months.
This trial will assess the efficacy and side effects of antipsychotics and create a standard clinical cohort with a multi-dimensional index assessment of antipsychotic treatment for schizophrenia patients.
This study aims to set up an individualized preferred treatment prediction model through the genetic analysis of patients using different kinds of antipsychotics.
In this paper, we focus on a Kirchhoff-type equation with singular potential and critical exponent. By virtue of the generalized version of Lions-type theorem and the Nehari–Pohožaev manifold, we established the existence of Nehari–Pohožaev-type ground state solutions to the mentioned equation. Some recent results from the literature are generally improved and extended.
The coexistence of underweight (UW) and overweight (OW)/obese (OB) at the population level is known to affect iron deficiency (ID) anaemia (IDA), but how the weight status affects erythropoiesis during pregnancy is less clear at a population scale. This study investigated associations between the pre-pregnancy BMI (pBMI) and erythropoiesis-related nutritional deficiencies.
Anthropometry, blood biochemistry and 24-h dietary recall data were collected during prenatal care visits. The weight status was defined based on the pBMI. Mild nutrition deficiency-related erythropoiesis was defined if individuals had an ID, folate depletion or a vitamin B12 deficiency.
The Nationwide Nutrition and Health Survey in Taiwan (Pregnant NAHSIT 2017–2019).
We included 1456 women aged 20 to 45 years with singleton pregnancies.
Among these pregnant women, 9·6 % were UW, and 29·2 % were either OW (15·8 %) or OB (13·4 %). A U-shaped association between the pBMI and IDA was observed, with decreased odds (OR; 95 % CI) for OW subjects (0·6; 95 % CI (0·4, 0·9)) but increased odds for UW (1·2; 95 % CI (0·8, 2·0)) and OB subjects (1·2; 95 % CI (0·8, 1·8)). The pBMI was positively correlated with the prevalence of a mild nutritional deficiency. Compared to normal weight, OB pregnant women had 3·4-fold (3·4; 95 % CI (1·4, 8·1)) higher odds for multiple mild nutritional deficiencies, while UW individuals had lowest odds (0·3; 95 % CI (0·1, 1·2)). A dietary analysis showed negative relationships of pBMI with energy, carbohydrates, protein, Fe and folate intakes, but positive relationship with fat intakes.
The pre-pregnancy weight status can possibly serve as a good nutritional screening tool for preventing IDA during pregnancy.
This article investigates the optimal hedging problem of the European contingent claims written on non-tradable assets. We assume that the risky assets satisfy jump diffusion models with a common jump process which reflects the correlated jump risk. The non-tradable asset and jump risk lead to an incomplete financial market. Hence, the cross-hedging method will be used to reduce the potential risk of the contingent claims seller. First, we obtain an explicit closed-form solution for the locally risk-minimizing hedging strategies of the European contingent claims by using the Föllmer–Schweizer decomposition. Then, we consider the hedging for a European call option as a special case. The value of the European call option under the minimal martingale measure is derived by the Fourier transform method. Next, some semi-closed solution formulae of the locally risk-minimizing hedging strategies for the European call option are obtained. Finally, some numerical examples are provided to illustrate the sensitivities of the optimal hedging strategies. By comparing the optimal hedging strategies when the underlying asset is a non-tradable asset or a tradable asset, we find that the liquidity risk has a significant impact on the optimal hedging strategies.
The aim of this study was to evaluate the safety and efficacy of the Cardi-O-Fix plug used for the treatment of muscular ventricular septal defects.
We retrospectively reviewed the medical records of five patients with muscular ventricular septal defects who underwent transcatheter closure using the Cardi-O-Fix Plug, from November 2017 to August 2019. The median age was 5.1 years (range: 3.2–6.5). Their median body weight was 18.1 kg (range: 13.4–21.8). All the patients underwent detailed two-dimensional Doppler and colour flow imaging by transthoracic echocardiography. The left ventricular median defect size of the muscular ventricular septal defects was 5.6 mm (range: 5.3–7.0). The right ventricular median defect size of the muscular ventricular septal defects was 3.9 mm (range: 3.3–4.7). All the procedures were performed on beating hearts.
All the patients underwent successful device implantation with no displacement or detachment, they have complete echocardiographic closure at the 1-year follow-up. There were no occluder-related arrhythmia, chordae tendineae rupture, tricuspid insufficiency, aortic regurgitation, haemolysis, or embolisation.
Application of the Cardi-O-Fix plug appears to be a feasible, safe, and effective treatment option for patients with muscular ventricular septal defects. Longer follow-up periods are warranted to prove the conclusion for long-term outcomes.
Robots of next-generation physically interact with the world rather than be caged in a controlled area, and they need to make contact with the open-ended environment to perform their task. Compliant robot links offer intrinsic mechanical compliance for addressing the safety issue for physical human–robot interactions (pHRI). However, many important research questions are yet to be answered. For instance, how do system parameters, for example, mechanical compliance, motor torque, impact velocities, and so on, affect the impact force? how to formulate system impact dynamics of compliant robots, and how to size their geometric dimensions to maximize impact force reduction. In this paper, we present a parametric study of compliant link (CL) design for safe pHRI. We first present a theoretical model of the pHRI system that is comprised of robot dynamics, an impact contact model, and dummy head dynamics. After experimentally validating the theoretical model, we then systematically study the effects of CL parameters on the impact force in more detail. Specifically, we explore how the design and actuation parameters affect the impact force of pHRI system. Based on the parametric studies of the CL design, we propose a step-by-step process and a list of concrete guidelines for designing CL with safety constraints in pHRI. We further conduct a simulation case study to validate this design process and design guidelines.
To determine if specific dietary patterns are associated with breast cancer (BC) risk in Chinese women.
Latent class analysis (LCA) was performed to identify generic dietary patterns based on daily food-frequency data.
The Chinese Wuxi Exposure and Breast Cancer Study (2013–2014).
A population-based case–control study (695 cases, 804 controls).
Four dietary patterns were identified, Prudent, Chinese traditional, Western and Picky; the proportion in the controls and cases was 0·30/0·32/0·16/0·23 and 0·29/0·26/0·11/0·33, respectively. Women in Picky class were characterised by higher extreme probabilities of non-consumption of specific foods, the highest probabilities of consumption of pickled foods and the lowest probabilities of consumption of cereals, soya foods and nuts. Compared with Prudent class, Picky class was associated with a higher risk (OR = 1·42, 95 % CI 1·06, 1·90), while the relevant association was only in post- (OR = 1·44, 95 % CI 1·01, 2·05) but not in premenopausal women. The Western class characterised by high-protein, high-fat and high-sugar foods, and the Chinese traditional class characterised by typical consumption of soya foods and white meat over red meat, both of them showed no difference in BC risk compared with Prudent class did.
LCA captures the heterogeneity of individuals embedded in the population and could be a useful approach in the study of dietary pattern and disease. Our results indicated that the Picky class might have a positive association with the risk of BC.
During the COVID-19 pandemic, the use of telemedicine as a way to reduce COVID-19 infections was noted and consequently deregulated. However, the degree of telemedicine regulation varies from country to country, which may alter the widespread use of telemedicine. This study aimed to clarify the telepsychiatry regulations for each collaborating country/region before and during the COVID-19 pandemic.
We used snowball sampling within a global network of international telepsychiatry experts. Thirty collaborators from 17 different countries/regions responded to a questionnaire on barriers to the use and implementation of telepsychiatric care, including policy factors such as regulations and reimbursement at the end of 2019 and as of May 2020.
Thirteen of 17 regions reported a relaxation of regulations due to the pandemic; consequently, all regions surveyed stated that telepsychiatry was now possible within their public healthcare systems. In some regions, restrictions on prescription medications allowed via telepsychiatry were eased, but in 11 of the 17 regions, there were still restrictions on prescribing medications via telepsychiatry. Lower insurance reimbursement amounts for telepsychiatry consultations v. in-person consultations were reevaluated in four regions, and consequently, in 15 regions telepsychiatry services were reimbursed at the same rate (or higher) than in-person consultations during the COVID-19 pandemic.
Our results confirm that, due to COVID-19, the majority of countries surveyed are altering telemedicine regulations that had previously restricted the spread of telemedicine. These findings provide information that could guide future policy and regulatory decisions, which facilitate greater scale and spread of telepsychiatry globally.
Three-dimensional porous materials with the hydrophobic/oleophilic surface have attracted significant interest in the fields of oil/water separation. In this paper, superhydrophobic magnetic polyurethane sponge was fabricated by the self-polymerization of dopamine to bind the Fe3O4 nanoparticles tightly on the sponge and then soaking in cheap stearic acid aqueous solution. The obtained sponge has the superhydrophobic property and good magnetic property. The surface structure, composition, and properties of the modified sponges were characterized by scanning electron microscopy, energy dispersive spectrometer, Fourier-transform infrared spectrum, and water contact angle (WCA) measurements. The as-prepared superhydrophobic magnetic sponge was able to collect a wide range of oils and organic solvents from oil–water mixture with an absorption capacity up to 16–60 times of its own weight. Under an external magnetic field, it can be guided to a designated area. In addition, combined with the vacuum system, continuous oil separation can be carried out, which is of great significance for removing a good deal of dirty oil on the water surface. Furthermore, the WCA of sponge remains above 141°, and the oil absorption is basically unchanged through repeated cyclic experiments.
Shifts in the maternal gut microbiota have been implicated in the development of gestational diabetes mellitus (GDM). Understanding the interaction between gut microbiota and host glucose metabolism will provide a new target of prediction and treatment. In this nested case-control study, we aimed to investigate the causal effects of gut microbiota from GDM patients on the glucose metabolism of germ-free (GF) mice. Stool and peripheral blood samples, as well as clinical information, were collected from 45 GDM patients and 45 healthy controls (matched by age and prepregnancy body mass index (BMI)) in the first and second trimester. Gut microbiota profiles were explored by next-generation sequencing of the 16S rRNA gene, and inflammatory factors in peripheral blood were analyzed by enzyme-linked immunosorbent assay. Fecal samples from GDM and non-GDM donors were transferred to GF mice. The gut microbiota of women with GDM showed reduced richness, specifically decreased Bacteroides and Akkermansia, as well as increased Faecalibacterium. The relative abundance of Akkermansia was negatively associated with blood glucose levels, and the relative abundance of Faecalibacterium was positively related to inflammatory factor concentrations. The transfer of fecal microbiota from GDM and non-GDM donors to GF mice resulted in different gut microbiota colonization patterns, and hyperglycemia was induced in mice that received GDM donor microbiota. These results suggested that the shifting pattern of gut microbiota in GDM patients contributed to disease pathogenesis.
The Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a public health emergency of international concern. The current study aims to explore whether the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are associated with the development of death in patients with COVID-19. A total of 131 patients diagnosed with COVID-19 from 13 February 2020 to 14 March 2020 in a hospital in Wuhan designated for treating COVID-19 were enrolled in the current study. These 131 patients had a median age of 64 years old (interquartile range: 56–71 years old). Furthermore, among these patients, 111 (91.8%) patients were discharged and 12 (9.2%) patients died in the hospital. The pooled analysis revealed that the NLR at admission was significantly elevated for non-survivors, when compared to survivors (P < 0.001). The NLR of 3.338 was associated with all-cause mortality, with a sensitivity of 100.0% and a specificity of 84.0% (area under the curve (AUC): 0.963, 95% confidence interval (CI) 0.911–1.000; P < 0.001). In view of the small number of deaths (n = 12) in the current study, NLR of 2.306 might have potential value for helping clinicians to identify patients with severe COVID-19, with a sensitivity of 100.0% and a specificity of 56.7% (AUC: 0.729, 95% CI 0.563–0.892; P = 0.063). The NLR was significantly associated with the development of death in patients with COVID-19. Hence, NLR is a useful biomarker to predict the all-cause mortality of COVID-19.
With world population senescence and globalization, more present-day older adults will evince cognitive aging that is influenced over a longer life span by a wide range of social practices and motivational beliefs from cultural groups across the world. Although there is no dispute that brain structure and function aggregate biological and experiential influences, a useful framework is still needed regarding the specific neural mechanisms underlying the exchange between biology and experience with age, and the effect on cognition. We introduce a predictive coding framework of the aging cognitive brain that views the older brain as making predictions about the environment based on a lifetime of experience in it. The influence of cultural experiences in shaping the aging predictive brain then reflects individual differences in processing social signals about appropriate or inappropriate behaviors and cognitive styles amid neural resources changes. We briefly annotate relevant findings on age effects and cultural differences in neurocognitive processing. We further review findings showing that cultural cognitive differences are present in children, persist in young adulthood, and are either maintained or accentuated in older adulthood. Finally, we consider that the predictive aging brain is an enculturated one, reflecting the accumulation of a lifetime of experiences that have fortified culture-specific modes of thought and neural processing in older adults.
Antibiotics are designed to affect gut microbiota and subsequently gut homeostasis. However, limited information exists about short- and long-term effects of early antibiotic intervention (EAI) on gut homeostasis (especially for the small intestine) of pigs following antibiotic withdrawal. We investigated the impact of EAI on specific bacterial communities, microbial metabolites and mucosal immune parameters in the small intestine of later-growth-stage pigs fed with diets differing in CP levels. Eighteen litters of piglets were fed creep feed with or without antibiotics from day 7 to day 42. At day 42, pigs within each group were offered a normal- or low-CP diet. Five pigs per group were slaughtered at days 77 and 120. At day 77, EAI increased Enterobacteriaceae counts in the jejunum and ileum and decreased Bifidobacterium counts in the jejunum and ileum (P < 0.05). Moreover, tryptamine, putrescine, secretory immunoglobulin (Ig) A and IgG concentrations in the ileum and interleukin-10 (IL-10) mRNA and protein levels in the jejunum and ileum were decreased in pigs with EAI (P < 0.05). At day 120, EAI only suppressed Clostridium cluster XIVa counts in the jejunum and ileum (P < 0.05). These results suggest that EAI has a short-term effect on specific bacterial communities, amino acid decarboxylation and mucosal immune parameters in the small intestine (particularly in the ileum). At days 77 and 120, feeding a low-CP diet affected Bifidobacterium, Clostridium cluster IV, Clostridium cluster XIVa and Enterobacteriaceae counts in the jejunum or ileum (P < 0.05). Moreover, feeding a low-CP diet increased the concentrations of Igs in the jejunum and decreased pro-inflammatory cytokines levels in the jejunum and ileum (P < 0.05). At day 120, feeding a low-CP diet increased short-chain fatty acid concentrations, reduced ammonia and spermidine concentrations and up-regulated genes related to barrier function in the jejunum and ileum (P < 0.05). These results suggest that feeding a low-CP diet changes specific bacterial communities and intestinal metabolite concentrations and modifies mucosal immune parameters. These findings contribute to our understanding on the duration of the impact of EAI on gut homeostasis and may provide basis data for nutritional modification in young pigs after antibiotic treatment.
Salmonella is a leading cause of foodborne outbreaks in Taiwan. On 27 April 2018, a salmonellosis outbreak among customers of a restaurant was reported to the Taiwan CDC. We investigated the outbreak to identify infection sources and prevent further transmission. We interviewed ill customers and their dining companions. We conducted a case-control study to identify foods associated with the illness. Case-patients were those who had diarrhoea within 72 h after eating at the restaurant during 16–27 April 2018. Specimens, food samples and environmental samples were collected and tested for enteric pathogens. Salmonella isolates were analysed with pulse-field gel electrophoresis and whole-genome sequencing. We inspected the restaurant sanitation and reviewed kitchen surveillance camera recordings. We identified 47 case-patients, including one decedent. Compared with 44 controls, case-patients were more likely to have had a French toast sandwich (OR: 102.4; 95% CI: 18.7–952.3). Salmonella Enteritidis isolates from 16 case-patients shared an indistinguishable genotype. Camera recordings revealed eggshell contamination, long holding time at room temperature and use of leftovers during implicated food preparation. Recommendations for restaurant egg-containing food preparation are to use pasteurised egg products and ensure a high enough cooking temperature and long enough cooking time to prevent Salmonella contamination.
Fluid motion has two well-known fundamental processes: the vector transverse process characterized by vorticity, and the scalar longitudinal process consisting of a sound mode and an entropy mode, characterized by dilatation and thermodynamic variables. The existing theories for the sound mode involve the multi-variable issue and its associated difficulty of source identification. In this paper, we define the source of sound inside the fluid by the objective causality inherent in dynamic equations relevant to a longitudinal process, which naturally favours the material time-rate operator
rather than the local time-rate operator
, and describes the sound mode by inhomogeneous advective wave equations. The sources of sound physical production inside the fluid are then examined at two levels. For the conventional formulation in terms of thermodynamic variables at the first level, we show that the universal kinematic source can be condensed to a scalar invariant of the surface deformation tensor. Further, in the formulation in terms of dilatation at the second level, we find that the sound mode in viscous and heat-conducting flow has sources from rich nonlinear couplings of vorticity, entropy and surface deformation, which cannot be disclosed at the first level. Preliminary numerical demonstration of the theoretical findings is made for two typical compressible flows, i.e. the interaction of two corotating Gaussian vortices and the unsteady type IV shock/shock interaction. The results obtained in this study provide a new theoretical basis for, and physical insight into, understanding various nonlinear longitudinal processes and the interactions therein.
The rhoptry kinase 18 of Toxoplasma gondii (TgROP18) has been identified as a key virulence factor that allows the parasite to escape from host immune defences and promotes its proliferation in host cells. Although much research is focused on the interaction between host cells and TgROP18, the development of monoclonal antibodies (mAbs) against TgROP18 has not been reported till date. To produce mAbs targeting TgROP18, two hybridomas secreting mAbs against TgROP18, designated as A1 and T2, were generated using cell fusion technology. The subtypes of the A1 and T2 mAbs were identified as IgG3 λ and IgM κ, and peptide scanning revealed that the core sequences of the antigenic epitopes were 180LRAQRRRSELVFE192 and 351NYFLLMMRAEADM363, respectively. The T2 mAb specifically reacted with both T. gondii type I and Chinese I, but not with T. gondii type II, Plasmodium falciparum or Schistosoma japonicum. Finally, the sequences of heavy chain and light chain complementarity-determining regions of T2 were amplified, cloned and characterized, making the modification of the mAb feasible in the future. The development of mAbs against TgROP18 would aid the investigation of the molecular mechanisms underlying the modulation of host cellular functions by TgROP18, and in the development of strategies to diagnose and treat Toxoplasmosis.
Major depressive disorder (MDD) is highly heterogeneous and can be classified as treatment-resistant depression (TRD) or antidepressant-responsive depression (non-TRD) based on patients' responses to antidepressant treatment. Methods for distinguishing between TRD and non-TRD are critical clinical concerns. Deficits of cortical inhibition (CI) have been reported to play an influential role in the pathophysiology of MDD. Whether TRD patients' CI is more impaired than that of non-TRD patients remains unclear.
Paired-pulse transcranial magnetic stimulation (ppTMS) was used to measure cortical inhibitory function including GABAA- and GABAB-receptor-related CI and cortical excitatory function including glutamate-receptor-related intracortical facilitation (ICF). We recruited 36 healthy controls (HC) and 36 patients with MDD (non-TRD, n = 16; TRD, n = 20). All participants received evaluations for depression severity and ppTMS examinations. Non-TRD patients received an additional ppTMS examination after 3 months of treatment with the SSRI escitalopram.
Patients with TRD exhibited reduced short-interval intracortical inhibition (SICI) and long-interval intracortical inhibition (LICI), as shown by abnormally higher estimates, than those with non-TRD or HC (F = 11.030, p < 0.001; F = 10.309, p < 0.001, respectively). After an adequate trial of escitalopram treatment, the LICI of non-TRD reduced significantly (t = − 3.628, p < 0.001), whereas the ICF remained lower than that of HC and showed no difference from pretreatment non-TRD.
TRD was characterized by relatively reduced CI, including both GABAA- and GABAB-receptor-mediated neurons while non-TRD preserved partial CI. In non-TRD, SSRIs may mainly modulate GABAB-receptor-related LICI. Our findings revealed distinguishable features of CI in antidepressant-resistant and responsive major depression.
Underground Nuclear Astrophysics in China (JUNA) will take the advantage of the ultra-low background in Jinping underground lab. High current accelerator with an ECR source and detectors were commissioned. JUNA plans to study directly a number of nuclear reactions important to hydrostatic stellar evolution at their relevant stellar energies. At the first period, JUNA aims at the direct measurements of 25Mg(p,γ)26 Al, 19F(p,α) 16 O, 13C(α, n) 16O and 12C(α,γ) 16O near the Gamow window. The current progress of JUNA will be given.
Seed reserves play vital roles in seed germination and seedling growth and their variation may be related to various environment factors, plant traits and phylogenetic history. Here, the evolutionary correlation associated with seed mass and altitude and carbon (C), nitrogen (N) and phosphorus (P) allocation of seeds among 253 alpine herbaceous plants was tested. In this study, phylogeny had strong limitations on nutrient allocation of seeds across species, and species from younger phylogenetic groups tended to have higher N and P contents, which might be considered as the evolutionary selection of seed plants. Higher seed N and P content would help seedlings to gain more survival chance and stronger competitive capacity, and their progeny would be more likely to be preserved. When phylogeny was considered, altitude only had a significant positive effect on P content, but the negative effects on seed mass were all expressed. The independent effects of altitude and seed mass suggest that the nutrient allocation of seeds might be affected by both environment and plant traits. In addition, altitude and seed mass displayed partial overlapping effects on nutrient allocation of seeds. The negative effects of seed mass were affected slightly by altitude, whereas altitude only had a significant positive effect on P content when seed mass was controlled. Above all, seed P content showed obvious and general correlations with seed mass, altitude and age of clade, which indicated that higher seed P content might be an adaptive selection of species associated with growth and survival of progeny.
The Ordos Basin is the largest and most important intracontinental sedimentary depression in China, and a significant amount of crude oil resources has developed within this Mesozoic formation. High-grade organic-rich shale is prevalent in the large-scale areas of the Chang 7 sedimentary stage and provides essential hydrocarbon resources for abundant oil enrichment in the Mesozoic. This research investigated the geochemical characteristics of Chang 7 shale using core samples and well logs and via laboratory tests. In addition, the microscopic components of the shale organic matter (OM), biological marker compounds, carbon isotopes, enrichment grade of trace elements, and elemental ratio were analysed systematically. Moreover, the aspects related to the shale OM source, sedimentary environment and resource potential were evaluated. Our results revealed that spherical alginate and calcium spherical alginate were predominant in the micropetrological components of the shale. Many biomarkers, including n-alkanes, steranes and terpanes, were detected in the gas chromatography – mass spectrometry spectra. An analysis of n-alkanes, regular sterane shapes (C21−/C22− and C26+C27/C28+C29), odd–even predominance index (OEP) and carbon preference index (CPI) values and carbon isotope distributions showed that OM was produced from aquatic organisms. The indicators of trace elements, such as Sr/Ba and V/V+Ni, combined with the biomarker compound in Pr/Ph and the gammacerane index showed the presence of a semi-deep – deep lake environment containing fresh–brackish water. In addition, the hydrocarbon conversion rate index and shale rock pyrolysis parameters revealed that Chang 7 has a high hydrocarbon generation ability and hydrocarbon expulsion efficiency.