Miracle-dz/UniFAR-FTUs huggingface dataset:
Engineered Fc-glycosylation switch to eliminate antibody effector function

ABSTRACT Antibodies mediate effector functions through Fcγ receptor (FcγR) interactions and complement activation, causing cytokine release, degranulation, phagocytosis, and cell death. They are often undesired for development of therapeutic antibodies where only antigen binding or neutralization would be ideal. Effector elimination has been successful with extensive mutagenesis, but these approaches can potentially lead to manufacturability and immunogenicity issues. By switching the native glycosylation site from position 297 to 298, we created alternative antibody glycosylation variants in the receptor interaction interface as a novel strategy to eliminate the effector functions. The engineered glycosylation site at Asn298 was confirmed by SDS-PAGE, mass spectrometry, and X-ray crystallography (PDB code 6X3I). The lead NNAS mutant (S298N/T299A/Y300S) shows no detectable binding to mouse or human FcγRs by surface plasmon resonance analyses. The effector functions of the mutant are completely eliminated when measured in antibody-dependent cell-meditated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) assays. In vivo, the NNAS mutant made on an antibody against a human lymphocyte antigen does not deplete T cells or B cells in transgenic mice, in contrast to wild-type antibody. Structural study confirms the successful glycosylation switch to the engineered Asn298 site. The engineered glycosylation would clash with approaching FcγRs based on reported Fc-FcγR co-crystal structures. In addition, the NNAS mutants of multiple antibodies retain binding to antigens and neonatal Fc receptor, exhibit comparable purification yields and thermal stability, and display normal circulation half-life in mice and non-human primate. Our work provides a novel approach for generating therapeutic antibodies devoid of any ADCC and CDC activities with potentially lower immunogenicity.
Host‐plant availability drives the spatiotemporal dynamics of interacting metapopulations across a fragmented landscape

Abstract The dynamics of ecological communities depend partly on species interactions within and among trophic levels. Experimental work has demonstrated the impact of species interactions on the species involved, but it remains unclear whether these effects can also be detected in long‐term time series across heterogeneous landscapes. We analyzed a 19‐yr time series of patch occupancy by the Glanville fritillary butterfly Melitaea cinxia, its specialist parasitoid wasp Cotesia melitaearum, and the specialist fungal pathogen Podosphaera plantaginis infecting Plantago lanceolata, a host plant of the Glanville fritillary. These species share a network of more than 4,000 habitat patches in the Åland islands, providing a metacommunity data set of unique spatial and temporal resolution. To assess the influence of interactions among the butterfly, parasitoid, and mildew on metacommunity dynamics, we modeled local colonization and extinction rates of each species while including or excluding the presence of potentially interacting species in the previous year as predictors. The metapopulation dynamics of all focal species varied both along a gradient in host plant abundance, and spatially as indicated by strong effects of local connectivity. Colonization and to a lesser extent extinction rates depended also on the presence of interacting species within patches. However, the directions of most effects differed from expectations based on previous experimental and modeling work, and the inferred influence of species interactions on observed metacommunity dynamics was limited. These results suggest that although local interactions among the butterfly, parasitoid, and mildew occur, their roles in metacommunity spatiotemporal dynamics are relatively weak. Instead, all species respond to variation in plant abundance, which may in turn fluctuate in response to variation in climate, land use, or other environmental factors.
The cytokine profile of menstrual blood

The menstrual cycle is regulated by a complex interplay between endometrial epithelial cells, endothelial cells, immune cells, and sex hormones. To communicate, cells secrete cytokines that have multiple and diverse effects on recipient cells. Knowledge of how these cells interact in the uterus is insufficient. Menstrual blood is easily accessible and provides a source to study menstrual cycle physiology. This study aimed to determine the cytokine profile in menstrual blood plasma and investigate the differences in cytokine profiles between menstrual and peripheral blood plasma. Several previous studies indicate an improved chance of embryo implantation after endometrial scratching. Consequently, our secondary aim was to compare the menstrual blood cytokine profile before and after luteal phase endometrial scratching.
Effects of exogenous C18 unsaturated fatty acids on milk lipid synthesis in bovine mammary epithelial cells

Abstract We determined the effects of a combination of C18 unsaturated fatty acids (C18-UFAs) consisting of oleic, linoleic, and linolenic acids on milk lipogenesis in bovine mammary epithelial cells (BMECs). By orthogonal experiments to determine cellular triacylglycerol (TAG) accumulation, a combination of 200 μmol/l C18 : 1, 50 μmol/l C18 : 2, and 2 μmol/l C18 : 3 was selected as C18-UFAs combination treatment, and culture in medium containing fatty acid-free bovine serum albumin was used as the control. The expression of genes related to milk lipid synthesis and intracellular FA composition was measured. The results showed that cytosolic TAG formation was higher under C18-UFAs treatment than under control treatment. The mRNA expression of acetyl-CoA carboxylase-α (ACACA), fatty acid synthase (FASN), and peroxisome proliferator-activated receptor gamma (PPARG) did not differ between treatments. The abundance of stearoyl-CoA desaturase (SCD) and acyl-CoA synthetase long-chain family member 1 (ACSL1) was higher, whereas that of sterol regulatory element binding transcription factor 1 (SREBF-1) was lower after C18-UFAs treatment compared to control treatment. The C16 : 0 and SFA content was decreased following C18-UFAs treatment compared to control treatment, while the cis-9 C18 : 1 and UFA content was increased. In conclusion, C18-UFAs could stimulate triglyceride accumulation, increase the cellular UFA concentration, and regulate lipogenic genes in BMECs.
Impact of the multidisciplinary antimicrobial stewardship team intervention focusing on carbapenem de‐escalation: A single‐centre and interrupted time series analysis

As a result of the constant increase in carbapenem resistance amongst gram‐negative bacteria in several countries, the inappropriate use of carbapenems must be reduced. Antimicrobial stewardship programmes (ASPs) aim to improve carbapenem usage by implementing interventions, including the promotion of the de‐escalation (DE) strategy. Thus, this study aimed to evaluate the impact of this strategy on carbapenem use based on a clear definition of DE.
Comparative efficacy and safety of drug treatment for premature ejaculation: A systemic review and Bayesian network meta‐analysis

To assess the comparative efficacy and safety of drug treatments for premature ejaculation. A systemic review and Bayesian network meta‐analysis were executed on randomised controlled trials of drug interventions for premature ejaculation. Intravaginal ejaculation latency time and related adverse effects were outcome measures. A total of 44 RCTs with 11,008 patients were included in our NMA. In therapy <8 weeks, the ranking of drug efficacy was topical creams >selective serotonin reuptake inhibitor (SSRI)+ phosphodiesterase 5 inhibitor (PDE5i) > PDE5i > sertraline > clomipramine > paroxetine > dapoxetine 60 milligram (mg) > dapoxetine 30 mg > fluoxetine>citalopram > duloxetine>placebo. In therapy ≥ 8 weeks, the ranking of drug efficacy was SSRI + PDE5i > topical creams > paroxetine > tramadol > PDE5i > fluoxetine > dapoxetine 60 mg > dapoxetine 30 mg > clomipramine>citalopram > placebo. For total adverse events, clomipramine, dapoxetine 30 mg, dapoxetine 60 mg, paroxetine, PDE5i, SSRI + PDE5i and tramadol had a higher risk than placebo. In conclusion, in ≥8 weeks of therapy, the drug combination of SSRI + PDE5i was the most effective PE therapy. In <8 weeks of therapy, the efficacy of local anaesthetics was best. All drug treatments were ranked better than placebo. In general, drugs with better effects had more obvious side effects.
Coronavirus Disease 2019 Complicated by Multiple Simultaneous Intracerebral Hemorrhages

The relationship between coronavirus disease 2019 (COVID-19) and intracerebral hemorrhage remains unclear. We herein report a case of severe COVID-19 pneumonia complicated by multiple simultaneous intracerebral hemorrhages (MSICH). The patient died eight days after the episode of MSICH. No apparent coagulopathy was observed; however, extracorporeal membrane oxygenation and anticoagulation might have caused the occurrence of MSICH. Laboratory findings showed hypercoagulability, suggesting that thrombotic etiologies, such as sinus thrombosis or cerebral infarction, might also have caused MSICH. MSICH can occur as a fatal complication of COVID-19, and this should be considered when providing treatment.
The effect of vitamin D supplementation in treatment of children with autism spectrum disorder: a systematic review and meta-analysis of randomized controlled trials

ABSTRACT Objective: The effect of vitamin D supplementation on the risk of Autism Spectrum Disorder (ASD) is conflicting. The aim of this study was to estimate the efficacy of vitamin D supplementation on ASD in children. Methods: We conducted a meta-analysis of randomized controlled trials (RCTs) in which vitamin D supplementation was used as a therapy in children with ASD. The PubMed, PsychINFO, Cochrane CENTRAL library, Web of Science, and Cinahl databases were searched from inception to March 20, 2019, for all publications on vitamin D and ASD with no restrictions. Studies involving individuals aged <18 years diagnosed with ASD and with all functional outcomes assessed by measurement scales for ASD were included. Mean differences were pooled, and a meta-analysis was performed using a random-effects model due to differences between the individual RCTs. Results: There were five RCTs with 349 children with ASD in the review, of which three RCTs were included in the meta-analysis. Vitamin D supplementation indicated a small but significant improvement in hyperactivity scores (pooled MD: −3.20; 95% CI: [−6.06, −0.34]) with low heterogeneity (I2 = 10%, p = 0.33), but there were no other statistically significant differences in ASD symptoms between groups as measured by validated scales. Conclusion: Vitamin D supplementation appears to be beneficial for hyperactivity but not for core symptoms or other co-existing behaviors and conditions of ASD. Future RCTs with large sample sizes examining the effect of vitamin D supplementation on ASD among individuals with low serum vitamin D levels at baseline are needed.
Sentinel lymph node mapping for metastasis detection in colorectal cancer: a systematic review and meta-analysis.

INTRODUCTION controversy exists on the diagnostic performance of sentinel lymph node (SLN) mapping in colorectal cancer. This study aimed to provide a more precise estimation of its clinical significance. MATERIALS AND METHODS a systematic search of electronic databases was conducted to retrieve all relevant studies up to August 31st, 2019. Detection rate, sensitivity, and upstaging rate were pooled together, and a subgroup analysis was performed to identify factors that affect diagnostic performance. The prognostic value of upstaging was also explored. RESULTS sixty-eight studies were eligible and included. The pooled SLN detection rate was 0.93 (95 % CI, 0.91-0.94), with a significant higher rate in colon cancer or in studies including more than 100 patients. The overall sensitivity of the SLN procedure in colorectal cancer was 0.72 (95 % CI, 0.67-0.77). The tracers used were found to influence sensitivity. A mean weighted upstaging of 0.22 (95 % CI, 0.18-0.25) was identified. True upstaging, defined as micro-metastases, was 14 %. Upstaged patients were associated with worse overall survival (OS) when compared with node-negative patients (HR = 2.60, 95 % CI, 0.16-4.63). In addition, upstaged patients had a lower 5-year disease-free survival (DFS) rate than node-negative patients. CONCLUSION based on the results of the present meta-analysis, the SLN mapping procedure should focus on early stage patients to refine staging, since upstaging appeared to be a prognostic factor for DFS and OS. The SLN procedure can be recommended for colorectal cancer patients in addition to conventional resection.
Is The Fixed Mandibular 3-Implant Retained Prosthesis Safe and Predicable for full-arch Mandibular Prostheses? A Systematic Review.

OBJECTIVE To evaluate implant and prosthetic survival rates of full-arch rehabilitations retained by three implants in patients with edentulous mandibles. METHODS This systematic review was developed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The focused question addressed was: Are fixed mandibular 3-implant retained prostheses safe and predicable for full-arch mandibular prostheses? The Medline/PubMed and Cochrane Library databases were used to conduct the systematic search for clinical trials on fixed mandibular 3-implant retained prostheses published between 1999 and 2020. Only English-language studies that presented information on their implant and prosthetic survival were included. RESULTS A total of 302 studies were identified, of which 13 addressed the inclusion criteria. Additionally, 574 participants were included in these studies. As reported, 73 (4.57%) of 1596 implants failed, with a survival rate of 95.43%. In addition, the mean survival rate of the presented prostheses was 89.66%. The mean marginal bone loss was 1.09 mm. CONCLUSION Within the limitations of the present review, implant and prosthetic survival rates of fixed mandibular 3-implant retained prostheses were similar to those of full-arch mandibular prostheses retained by four or more implants. Further research exploring the topic are necessary. This article is protected by copyright. All rights reserved.
Direct Current Electrokinetic Particle Trapping in Insulator-based Microfluidics: Theory and Experiments.

The classic theory of direct-current (DC) insulator-based dielectrophoresis (iDEP) considers that, in order to elicit particle trapping, dielectro-phoretic (DEP) velocity counterbalances electrokinetic (EK) motion-i.e., electrophoresis (EP) and electroosmotic flow (EOF). However, the particle velocity DEP component has required empirical correction factors (sometimes as high as 600) to account for experimental observa-tions, suggesting the need for a refined model. Here, we show that, when applied to particle suspensions, a high-magnitude DC uniform electric field induces nonlinear particle velocities, leading to particle flow reversal beyond a critical field magnitude, referred to as the EK equilibrium condition. We further demonstrate that this particle motion can be described through an exploratory induced-charge EP nonlinear model. The model predictions were validated under an insulator-based microfluidic platform demonstrating predictive particle trapping for three different particle sizes (with an estimation error < 10%, not using correction factors). Our findings suggest that particle motion and trapping in 'DC-iDEP' devices are dominated by EP and EOF, rather than by DEP effects.
Benefit and risk of early intravenous heparin after thrombolysis in patients with acute ischemic stroke

We performed a retrospective analysis of the “Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China (TIMS‐China)” registry to explore the benefit and risk of intravenous thrombolysis (IVT) followed by intravenous heparin (IVH) in acute ischemic stroke (AIS) patients.
Novel C1q receptor-mediated signaling controls neural stem cell behavior and neurorepair

C1q plays a key role as a recognition molecule in the immune system, driving autocatalytic complement cascade activation and acting as an opsonin. We have previously reported a non-immune role of complement C1q modulating the migration and fate of human neural stem cells (hNSC); however, the mechanism underlying these effects has not yet been identified. Here, we show for the first time that C1q acts as a functional hNSC ligand, inducing intracellular signaling to control cell behavior. Using an unbiased screening strategy, we identified five transmembrane C1q signaling/receptor candidates in hNSC (CD44, GPR62, BAI1, c-MET, and ADCY5). We further investigated the interaction between C1q and CD44 , demonstrating that CD44 mediates C1q induced hNSC signaling and chemotaxis in vitro, and hNSC migration and functional repair in vivo after spinal cord injury. These results reveal a receptor-mediated mechanism for C1q modulation of NSC behavior and show that modification of C1q receptor expression can expand the therapeutic window for hNSC transplantation.
Recurrent abdominal pain among adolescents: trends and social inequality 1991–2018

Abstract Objectives The association between socioeconomic status and recurrent abdominal pain (RAP) among adolescents is an understudied issue. No study has examined whether such an association changes over time. The aim was to examine trends in RAP among adolescents in Denmark from 1991 to 2018, to examine whether there was social inequality in RAP and whether this inequality varied over time. Methods The study used data from the Danish part of the international Health Behaviour in School-aged Children (HBSC) study of nationally representative samples of 11-, 13- and 15-year-olds. This study pooled data from eight comparable surveys from 1991 to 2018, overall participation rate 88.0%, n=30,048. The definition of RAP was self-reported stomach-ache daily or several days per week during the past six months. We reported absolute inequality as prevalence difference in RAP between low and high socioeconomic status and relative inequality as odds ratio for RAP by socioeconomic status. Results In the entire study population, 5.6% reported RAP, 3.1% among boys and 7.8% among girls. There was a significant increase in RAP from 1991 to 2018 among boys and girls, test for trend, p<0.0001. The prevalence of RAP was significantly higher in low than high socioeconomic status, OR=1.63 (95% CI: 1.42–1.87). The absolute social inequality in RAP fluctuated with no consistent increasing or decreasing pattern. Conclusions The prevalence of RAP increased from 1991 to 2018. The prevalence was significantly higher among girls than among boys, and significantly higher in low socioeconomic status families. Professionals should be aware of RAP as common and potentially serious health problems among children and adolescents. In addition to clinical examination it is important to focus on improving the child’s quality of life, reduce parents’ and children’s concerns about the seriousness of the condition, and consider supplements to medicine use.
A single-institution retrospective analysis of the differences between 7th and 8th edition of the UICC TNM staging system in patients with advanced lung cancer.

OBJECTIVE The TNM (Tumor, Node, Metastasis) classiﬁcation of Union for International Cancer Control is a system describing the anatomical extent of the solid tumors that leads to staging and decision on the type of treatment. The latter TNM system (2017) as compared to the previous version (2010) has brought numerous changes. Our aim was to examine whether significant changes in the new TNM edition have altered the components of the TNM classification in patients and the stage of the disease to which they are ascribed. PATIENTS AND METHODS The study is retrospective and is based on radiological examination reports and case reports of 100 patients of the Department of Pneumonology, Allergology and Oncology of the Medical University in Lublin, Poland. One hundred randomly selected patients, who were hospitalized at the Clinic between 2013 and 2018 with primary lung cancer were enrolled in the study. The chi-square test, Mann-Whitney U test, Kruskal-Wallis test and an appropriate post-hoc test were used in statistical analysis. RESULTS It was calculated that the T descriptor evaluated as per TNM in revision 8th in comparison to revision 7th changed in 41% of patients, the M descriptor - in 29% of patients, which resulted in change in staging in 11 patients. In spite of this scale amendments, only three patients could be treated differently because of the change in the stage of the disease. CONCLUSIONS Changing the treatment method, including withdrawal from surgery, can help avoid unnecessary treatment, but on the other hand, may potentially reduce the patient's chances of survival by depriving them of the possibility of radical treatment.
The role of caregiver speech in supporting language development in infants and toddlers with autism spectrum disorder

Abstract Parents play an essential role in supporting child development by providing a safe home, proper nutrition, and rich educational opportunities. In this article we focus on the role of caregiver speech in supporting development of young children with autism spectrum disorder (ASD). We review studies from typically developing children and children with autism showing that rich and responsive caregiver speech supports language development. Autism intervention studies that target caregiver speech are reviewed as are recent scientific advances from studies of typical development. The strengths and weakness of different techniques for collecting language data from caregivers and children are reviewed, and natural language samples are recommended as best practice for language research in autism. We conclude that caregivers play a powerful role in shaping their children's development and encourage researchers to adapt parent-mediated intervention studies to acknowledge individual differences in parents by using a personalized medicine approach.
Prospective relations between sleep in preschool years and academic achievement at school entry

It is often assumed that adequate sleep is a key ingredient of children's school success. Research to date, however, suggests modest associations between child sleep and academic achievement. Adopting a developmental perspective, this report investigates the associations between age‐related changes in sleep across the preschool period and academic achievement at school entry. Sleep was assessed by actigraphy at ages 2, 3 and 4 among 128 children from mostly White middle‐class families, and their performance in reading and mathematics was tested in Grade 1. The results revealed that children whose sleep duration decreased more rapidly across the preschool period showed better performance in both reading and mathematics. These results suggest that age‐related developments may be a key characteristic of sleep in the preschool years.