Notes

Characterisation of the scientific phenotype within Phelan-McDermid symptoms.
The subgroup analyses of language performance showed positive effects of LF-rTMS among stroke patients with chronic aphasia and acute aphasia. LF-rTMS + SLT had effects on language performance that were superior to the sham rTMS + SLT and SLT alone. A shorter LF-rTMS duration benefited language performance more than a longer duration. Additionally, 20 min of LF-rTMS per session produced a positive effect on language ability for patients with aphasia after a stroke. No adverse events were reported. Conclusions LF-rTMS + SLT is an effective and safe method for patients with poststroke aphasia to improve their language performance. Additionally, the most commonly used LF-rTMS protocol for patients with aphasia after a stroke was 90% of the resting motor threshold 20 min per day, 5 days per week, for 2 weeks.
Clinical trials require significant resources, but benefits are only realized after trial completion and dissemination of results. We comprehensively assessed early discontinuation, registry results reporting, and publication by trial sponsor and subspecialty in urology trials.

We assessed trial registrations from 2007 to 2019 on ClinicalTrials.gov and publication data from PubMed®/MEDLINE®. Associations between sponsor or subspecialty with early discontinuation were assessed using Cox proportional hazards and results reporting or publication with logistic regression at 3 years after completion.

Of 8,636 trials 3,541 (41.0%) were completed and 999 (11.6%) were discontinued. Of completed trials 26.9% reported results and 21.6% were published. Sponsors included academic institutions (53.1%), industry (37.1%) and the U.S. government (9.8%). Academic-sponsored (adjusted HR 0.81, 95% CI 0.69-0.96, p=0.012) and government-sponsored trials (adjusted HR 0.62, 95% CI 0.49-0.78, p <0.001) were less likely thanfor urology trials.
Sponsor type is significantly associated with trial completion and dissemination. Government-sponsored trials had the best performance, while industry and academic-sponsored trials lagged in completion and results reporting, respectively. Subspecialty played a lesser role. Lack of dissemination remains a problem for urology trials.
We aimed to evaluate all-cause and cause-specific mortality in patients with systemic lupus erythematosus (SLE) and neuropsychiatric (NP) symptoms in the Netherlands between 2007-2018.

Patients visiting the tertiary referral NPSLE clinic of the Leiden University Medical Center were included. NP symptoms were attributed to SLE requiring treatment (major NPSLE) or to other and mild causes (minor/non-NPSLE). Municipal registries were checked for current status (alive/deceased). Standardized mortality ratios (SMRs) and 95% confidence intervals (CI) were calculated using data from the Dutch population. Rate ratio (RR) and 95% CI were calculated using direct standardization to compare mortality between major NPSLE and minor/non-NPSLE.

351 patients were included and 149 patients were classified as major NPSLE (42.5%). Compared with the general population, mortality was increased in major NPSLE (SMR 5.0 (95% CI 2.6-8.5)) and minor/non-NPSLE patients (SMR 3.7 (95% CI 2.2-6.0)). Compared with minor/non-NPSLE, mortality was similar in major NPSLE patients (RR 1.0 (95% CI 0.5-2.0)). Cause-specific mortality rates demonstrated an increased risk of death due to infections in both groups, whereas death due to cardiovascular disease was only increased in minor/non-NPSLE patients.

Mortality was increased in both major NPSLE and minor/non-NPSLE patients in comparison with the general population. There was no difference in mortality between major NPSLE and minor/non-NPSLE patients.
Mortality was increased in both major NPSLE and minor/non-NPSLE patients in comparison with the general population. There was no difference in mortality between major NPSLE and minor/non-NPSLE patients.Tremendous work has demonstrated the critical roles of genetics, epigenetics as well as their interplay in brain transcriptional regulations in the pathology of schizophrenia (SZ). https://www.selleckchem.com/products/gc376-sodium.html There is great success currently in the dissection of the genetic components underlying risk-conferring transcriptomic networks. However, the study of regulating effect of epigenetics in the etiopathogenesis of SZ still faces many challenges. In this work, we investigated DNA methylation and gene expression from the dorsolateral prefrontal cortex (DLPFC) region of schizophrenia patients and healthy controls using weighted correlation network approach. We identified and replicated two expression and two methylation modules significantly associated with SZ. Among them, one pair of expression and methylation modules were significantly overlapped in the module genes which were significantly enriched in astrocyte-associated functional pathways, and specifically expressed in astrocytes. Another two linked expression-methylation module pairs were involved ageing process with module genes mostly related to oligodendrocyte development and myelination, and specifically expressed in oligodendrocytes. Further examination of underlying quantitative trait loci (QTLs) showed significant enrichment in genetic risk of most psychiatric disorders for expression QTLs but not for methylation QTLs. These results support the coherence between methylation and gene expression at the network level, and suggest a combinatorial effect of genetics and epigenetics in regulating gene expression networks specific to glia cells in relation to SZ and ageing process.Monoclonal antibodies (mAbs) are among the fastest growing and most effective therapies for myriad diseases. Multispecific antibodies are an emerging class of novel therapeutics that can target more than one tumor- or immune-associated modulators per molecule. The combination of different binding affinities and target classes, such as soluble or membrane-bound antigens, within multispecific antibodies confers unique pharmacokinetic (PK) properties. Numerous factors affect an antibody's PK, with affinity to the neonatal Fc receptor (FcRn) a key determinant of half-life. Recent work has demonstrated the potential for humanized FcRn transgenic mice to predict the PK of mAbs in humans. However, such work has not been extended to multispecific antibodies. We engineered mAbs and multispecific antibodies with various Fc modifications to enhance antibody performance. PK analyses in humanized FcRn transgenic mouse (homozygous Tg32 and Tg276) and non-human primate (NHP) models showed that FcRn-binding mutations improved the plasma half-lives of the engineered mAbs and multispecific antibodies, while glycan engineering to eliminate effector function did not affect the PK compared with wild-type controls. Furthermore, results suggest that the homozygous Tg32 mouse model can replace NHP models to differentiate PK of variants during lead optimization, not only for wild-type mAbs but also for Fc-engineered mAbs and multispecific antibodies. This Tg32-mouse model would enable prediction of half-life and linear clearance of mAbs and multispecific antibodies in NHPs to guide the design of further pharmacology/safety studies in this species. The allometric exponent for clearance scaling from Tg32 mice to NHPs was estimated to be 0.91 for all antibodies.Purpose This study investigated whether maximum speech performance, more specifically, the ability to rapidly alternate between similar syllables during speech production, is associated with executive control abilities in a nonclinical young adult population. Method Seventy-eight young adult participants completed two speech tasks, both operationalized as maximum performance tasks, to index their articulatory control a diadochokinetic (DDK) task with nonword and real-word syllable sequences and a tongue-twister task. Additionally, participants completed three cognitive tasks, each covering one element of executive control (a Flanker interference task to index inhibitory control, a letter-number switching task to index cognitive switching, and an operation span task to index updating of working memory). Linear mixed-effects models were fitted to investigate how well maximum speech performance measures can be predicted by elements of executive control. Results Participants' cognitive switching ability was associated with their accuracy in both the DDK and tongue-twister speech tasks. Additionally, nonword DDK accuracy was more strongly associated with executive control than real-word DDK accuracy (which has to be interpreted with caution). None of the executive control abilities related to the maximum rates at which participants performed the two speech tasks. Conclusion These results underscore the association between maximum speech performance and executive control (cognitive switching in particular).Operation Warp Speed and global vaccine research efforts have succeeded in rapidly launching three vaccine candidates for coronavirus disease 2019 (COVID-19) into Phase III clinical trials. A recent letter from Centers for Disease Control and Prevention (CDC) Director Redfield underscored the possibility of "large-scale" distribution of a coronavirus vaccine as early as November 1, 2020. However, recent polling reveals that the majority of Americans remain skeptical of both the safety and efficacy of a potential Covid-19 vaccine. Even more troublesome is the fact that a comprehensive, collaborative vaccine marketing campaign has not been initiated to educate the U.S. public on and encourage widespread Covid-19 vaccination. Accordingly, this article lays out a plan of action, utilizing proven immunization marketing strategies and novel approaches, that could be used to combat vaccine hesitancy toward Covid-19. A vaccine may indeed be our ticket out of this pandemic, but targeted marketing is needed to increase public optimism toward that fact.
This study assessed the feasibility of integrating telehealth-assisted home-based specialist palliative care (TH-SPC) into a rural community setting.

This was a prospective mixed-methods pilot study conducted in rural Victoria, Australia. Newly engaged adult patients and their caregivers of a community palliative-care service received video consultations with metropolitan-located specialist palliative-care physicians, alongside standard care. Those eligible patients who failed to receive TH-SPC were treated as a control group upon analysis. Data were collected over three months and at 30 days prior to death. Feasibility outcomes included efficiency of process, user satisfaction, clinical outcome and health-care metrics.

A total of 21 patients completed the study, with an average age of 70.4 years and an average survival of 5.8 months. Fourteen patients received TH-SPC, and seven received standard care alone. Patient-caregiver feedback for TH-SPC showed a high level of overall satisfaction. Compared to standard care, the TH-SPC group demonstrated less functional decline from baseline at two weeks (Australia-modified Karnofsky Performance Status -1.35 vs. -12.30,
 = 0.067) and three months (8.48 vs. -10.79,
 = 0.04) after the intervention. At 30 days prior to death, functional status remained better in the TH-SPC group, with fewer per capita community palliative-care nursing visits (5.46 vs. 9.32, effect size = 0.7), general practitioner visits (0.13 vs. 3.88, effect size = 1.34) and hospital admissions (0.02 vs. 0.2, effect size = 0.65).

TH-SPC was successfully integrated into rural community-based palliative care, with potential benefits in performance status preservation and health-care resource utilisation.
TH-SPC was successfully integrated into rural community-based palliative care, with potential benefits in performance status preservation and health-care resource utilisation.
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