Miracle-dz/UniFAR-FTUs huggingface dataset:
Reply to: Comment on “The Role of High‐Intensity Focused Ultrasound as a Symptomatic Treatment for Parkinson's Disease”

MR-guided focused ultrasound (MRgFUS) neurosurgery is a new option for treatment of Parkinson’s disease (PD). In a recent issue of Movement Disorders, Moosa and colleagues published an attractive and informative review article about the treatment of PD with MRgFUS. However, the review seems inaccurate in some places. First, it was stated in the review that Schlesinger and colleagues published the first case series describing the use of MRgFUS for treatment of tremor-dominant PD. But as far as we know, the first case series describing MRgFUS for treatment of tremor-dominant PD was formally published in 2014 by Magara and colleagues. Second, as was shown in the text, the review mainly talked about different surgical targets of MRgFUS for PD. Although mainstream surgical targets for PD such as the ventral intermediate nucleus (VIM), STN, and GPi were discussed in detail in the review, other surgical targets including the pallidothalamic tract (PTT) and ventral oralis posterior nucleus (VOP), which had also been used with favorable outcomes, were ignored. The authors stated that “We will discuss each of the surgical targets utilized to date,” but the surgical targets used to date were actually incompletely included, which may make physicians or patients mistakenly believe that only the 3 discussed targets can be tried when performing or receiving MRgFUS. Despite that the PTT and VOP have only been limitedly used as surgical targets for treatment of PD, their potential as effective targets, which has been observed in previous studies, should not be ignored. In addition, when talking about MRgFUS VIM thalamotomy, the authors mentioned that improvement in rigidity was also observed in Ito and colleagues’ study. Actually, in Ito et al’s study, they not only chose the VIM as the surgical target but also targeted the VOP. The VOP was considered to be associated with rigidity, and this was why Ito and colleagues chose to target it for a PD patient with rigidity. Therefore, there is a great possibility that the improvement in rigidity in Ito and colleagues’ study should result from the targeting of the VOP instead of the VIM. The possible value of ablating the VOP for improving rigidity deserves attention and needs further study. However, Moosa and colleagues did not mention the possible value of the VOP while talking about improvement in rigidity described in Ito et al’s study, which seems inappropriate. Yangyang Xu, MD, Qi He, MD, and Wei Wang, MD* Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu, China, and Department of Neonatology, West China Second University Hospital, Sichuan University, Chengdu, China
The Effects of Interrupting Sitting Time on Affect and State Anxiety in Children of Healthy Weight and Overweight: A Randomized Crossover Trial.

PURPOSE Sedentary time relates to higher anxiety and more negative affect in children. This study assessed whether interrupting sitting over 3 hours is sufficient to influence state anxiety, positive affect, or negative affect, and tested weight status as a moderator. METHODS Analyses were the second (preplanned) purpose of a larger study. Children (N = 61; age: mean [SD] = 9.5 [1.3]; 43% healthy weight) completed 2 experimental conditions: continuous sitting for 3 hours and sitting for 3 hours interrupted with walking for 3 minutes in every 30 minutes. State anxiety, positive affect, and negative affect were reported at pretest and posttest. Multilevel models for repeated measures assessed whether experimental condition predicted posttest scores. RESULTS Experimental condition was unrelated to posttest state anxiety or positive affect. Weight status moderated how experimental condition influenced posttest negative affect (P = .003). Negative affect was lower in the children of healthy weight after interrupted sitting (vs continuous sitting; β = -0.8; 95% confidence interval, -1.5 to 0.0, P = .05), but it was higher in the children with overweight/obesity after interrupted sitting (vs continuous sitting; β = 0.6; 95% confidence interval, 0.0 to 1.2, P = .06). CONCLUSIONS Interrupting sitting acutely reduced negative affect in children of healthy weight, but not in children with overweight. Further research is needed to better understand the potential emotional benefits of sitting interruptions in youth.
Sex differences in cognitive functioning of patients at-risk for psychosis and healthy controls: Results from the European Gene–Environment Interactions study

Abstract Background. Sex differences in cognitive functioning have long been recognized in schizophrenia patients and healthy controls (HC). However, few studies have focused on patients with an at-risk mental state (ARMS) for psychosis. Thus, the aim of the present study was to investigate sex differences in neurocognitive performance in ARMS patients compared with HC. Methods. The data analyzed in this study were collected within the multicenter European Gene–Environment Interactions study (11 centers). A total of 343 ARMS patients (158 women) and 67 HC subjects (33 women) were included. All participants completed a comprehensive neurocognitive battery. Linear mixed effects models were used to explore whether sex differences in cognitive functioning were present in the total group (main effect of sex) and whether sex differences were different for HC and ARMS (interaction between sex and group). Results. Women performed better in social cognition, speed of processing, and verbal learning than men regardless of whether they were ARMS or HC. However, only differences in speed of processing and verbal learning remained significant after correction for multiple testing. Additionally, ARMS patients displayed alterations in attention, current IQ, speed of processing, verbal learning, and working memory compared with HC. Conclusions. Findings indicate that sex differences in cognitive functioning in ARMS are similar to those seen between healthy men and women. Thus, it appears that sex differences in cognitive performance may not be specific for ARMS, a finding resembling that in patients with schizophrenic psychoses.
Foot-and-mouth disease epidemiology in relation to the physical, social and demographic farming landscape

The foot-and-mouth disease (FMD) virus poses a considerable threat both to farmers and to the wider economy should there be a future incursion into the UK. The most recent large-scale FMD epidemic in the UK was in 2001. Mathematical models were developed and used during this epidemic to aid decision-making about how to most e ectively control and eliminate it. While the epidemic was eventually brought to a halt, it resulted in a huge loss of livestock and is estimated to have cost the UK economy around ¿6 billion. The mathematical models predicted the overall spatial spread of FMD well, but had low predictive ability for identifying precisely which farm premises became infected over the course of the epidemic. This will in part have been due to the stochastic nature of the models. However, the transmission probability between two farm premises was represented as the Euclidean distance between their point locations, which is a crude representation of FMD transmission. Additionally, the premises' point location data contain inaccuracies, sometimes identifying the farmer's residential address rather than the farm itself which may be a long way away. Local FMD transmission occurs via contaminated fomites carried by people or vehicles between premises, or by infected particles being blown by wind between proximal elds. Given that these transmission mechanisms are thought to be related to having close eld boundaries, it is possible that some of the inaccuracy in model predictions is also due to imprecisely representing such transmission. In this thesis I use ne-scale geographical data of farm premises' eld locations to
Cell senescence altered the miRNA expression profile in porcine angular aqueous plexus cells

Purpose This study investigates the impact of aging on the miRNA expression profile in porcine angular aqueous plexus (AAP) cells, which are the porcine equivalent of human Schlemm’s canal endothelial cells. Methods AAP endothelial cells were isolated and cultured in physiologic (5% O2) or hyperoxic condition (40% O2) for 14 days to induce cell senescence. miRNA and protein expression profiles of control and senescent cells were analyzed with miRNA microarray and isobaric tags for relative and absolute quantification (iTRAQ), respectively. Results The miRNA microarray identified 33 differentially expressed miRNAs in senescent cells compared with controls (p<0.05), and quantitative real-time PCR (qRT-PCR) confirmed 12 of them (p<0.05). iTRAQ analysis identified 148 upregulated and 222 downregulated proteins (p<0.05, fold change>1.2). Bioinformatics analysis of miRNA microarray and proteomics data predicted that six out of seven miRNAs are associated with aqueous humor outflow by targeting integrin and the downstream pathways (Src/Rho kinase, focal adhesion kinase (FAK)/NO-cGMP), and one miRNA might influence gap junction by targeting the Inositol trisphosphate receptor (IP3R) /Protein kinase C (PKC) pathway. Conclusions This study identified miRNAs in senescent AAP cells that might regulate aqueous humor outflow by targeting proteins involved in focal adhesion, cytoskeleton, NO-cGMP signaling, and gap junction.
Reconstructing ribosomal genes from large scale total RNA meta-transcriptomic data

Abstract Motivation Technological advances in meta-transcriptomics have enabled a deeper understanding of the structure and function of microbial communities. ‘Total RNA’ meta-transcriptomics, sequencing of total reverse transcribed RNA, provides a unique opportunity to investigate both the structure and function of active microbial communities from all three domains of life simultaneously. A major step of this approach is the reconstruction of full-length taxonomic marker genes such as the small subunit ribosomal RNA. However, current tools for this purpose are mainly targeted towards analysis of amplicon and metagenomic data and thus lack the ability to handle the massive and complex datasets typically resulting from total RNA experiments. Results In this work, we introduce MetaRib, a new tool for reconstructing ribosomal gene sequences from total RNA meta-transcriptomic data. MetaRib is based on the popular rRNA assembly program EMIRGE, together with several improvements. We address the challenge posed by large complex datasets by integrating sub-assembly, dereplication and mapping in an iterative approach, with additional post-processing steps. We applied the method to both simulated and real-world datasets. Our results show that MetaRib can deal with larger datasets and recover more rRNA genes, which achieve around 60 times speedup and higher F1 score compared to EMIRGE in simulated datasets. In the real-world dataset, it shows similar trends but recovers more contigs compared with a previous analysis based on random sub-sampling, while enabling the comparison of individual contig abundances across samples for the first time. Availability and implementation The source code of MetaRib is freely available at https://github.com/yxxue/MetaRib. Contact yaxin.xue@uib.no or Inge.Jonassen@uib.no Supplementary information Supplementary data are available at Bioinformatics online.
Schistosomiasis and Bladder Cancer in Egypt: Truths and Myths

BACKGROUND: The gathered archeopathological evidence has confirmed that Schistosomiasis has been endemic in Ancient Egypt for over 500 decades. The association between Schistosoma hematobium and increase bladder cancer risk is also well acknowledged. However, over the years, there is a proved changing pattern of bladder cancer that needs to be investigated. AIM: We aim to discuss the truths and myths about bladder cancer and its association with Schistosomiasis in Egypt. METHODS: A cross-sectional, case-control study was performed to collect recent data on the topic. RESULTS: Of the reported cancer cases, 79.3% were transitional cell carcinoma (TCC), an additional 6% showed associated squamous features. Squamous cell carcinoma (SCC) constituted only 13.8% of cancer cases. Schistosomiasis was histologically confirmed in 19 cancer cases, only one was SCC. The relative frequency of TCC is increasing, while SCC is decreasing. There is no evidence that this pattern is related to smoking or environmental factors, as the incidence of lung cancer, is not proportionately increasing. CONCLUSION: The old concept that Schistosomiasis is associated with SCC should be revaluated as most cases are associated with TCC. Relying on the histopathology for confirmation of Schistosomiasis in our research studies appears to be non-accurate and leads to irrelevant results.
Age-related modulations of alpha and gamma brain activities underlying anticipation and distraction

Attention operates through top-down (TD) and bottom-up (BU) mechanisms. Recently, it has been shown that slow (alpha) frequencies index facilitatory and suppressive mechanisms of TD attention and faster (gamma) frequencies signal BU attentional capture. Ageing is characterized by increased behavioral distractibility, resulting from either a reduced efficiency of TD attention or an enhanced triggering of BU attention. However, only few studies have investigated the impact of ageing upon the oscillatory activities involved in TD and BU attention. MEG data were collected from 14 elderly and 14 matched young healthy human participants while performing the Competitive Attention Task. Elderly participants displayed (1) exacerbated behavioral distractibility, (2) altered TD suppressive mechanisms, indexed by a reduced alpha synchronization in task-irrelevant regions, (3) less prominent alpha peak-frequency differences between cortical regions, (4) a similar BU system activation indexed by gamma activity, and (5) a reduced activation of lateral prefrontal inhibitory control regions. These results show that the ageing-related increased distractibility is of TD origin.
Crosstalk Among Circadian Rhythm, Obesity and Allergy

The circadian clock system works not only as a cellular time-keeper but also as a coordinator for almost all physiological functions essential to maintaining human health. Therefore, disruptions or malfunctions of this system can cause many diseases and pre-symptomatic conditions. Indeed, previous studies have indicated that disrupted clock gene expression rhythm is closely related to obesity, and that allergic diseases can be regulated by controlling peripheral clocks in organs and tissues. Moreover, recent studies have found that obesity can lead to immune disorders. Accordingly, in this review, we assess the connection between obesity and allergy from the point of view of the circadian clock system anew and summarize the relationships among the circadian clock system, obesity, and allergy.
Paraben concentrations found in human body fluids do not exert steroidogenic effects in human granulosa primary cell cultures

Abstract In cosmetics and food products, parabens are widely used as antimicrobial agents. Reports have suggested that parabens may be linked to infertility, owing to their effects on basal steroidogenesis properties or their capacity to inflict mitochondrial damage. Despite growing concerns about parabens as endocrine disruptors, it is unclear whether they affect any of these actions in humans, particularly at environmentally relevant concentrations. In this work, an in vitro primary culture of human granulosa cells was used to evaluate steroidogenesis, based on the assessment of progesterone production and regulation of critical steroidogenic genes: CYP11A1, HSD3B1, CYP19A1, and HSD17B1. The effects of two commercially relevant parabens, methylparaben (MPB) and butylparaben (BPB), were screened. Cells were exposed to multiple concentrations ranging from relatively low (typical environmental exposure) to relatively high. The effect was assessed by the parabens’ ability to modify steroidogenic genes, progesterone or estradiol production, and on mitochondrial health, by evaluating mitochondrial activity as well as mtDNA content. Neither MPB nor BPB showed any effect over progesterone production or the expression of genes controlling steroid production. Only BPB affected the mitochondria, decreasing mtDNA content at supraphysiological concentrations (1000 nM). Prolonged exposure to these compounds produced no effects in neither of these parameters. In conclusion, neither MPB nor BPB significantly affected basal steroidogenesis in granulosa cells. Although evidence supporting paraben toxicity is prevalent, here we put forth evidence that suggests that parabens do not affect basal steroidogenesis in human granulosa cells.
A single administration of ‘microbial’ D-alanine to healthy volunteers augments reaction to negative emotions: A comparison with D-serine

Background: Activation of the glutamate N-methyl-D-aspartate receptor with its co-agonist D-serine has been shown to improve subjective mood in healthy volunteers. D-alanine is another potent N-methyl-D-aspartate receptor co-agonist which arises from the natural breakdown of host gut microbes, and is predominantly sequestered in the pituitary. This may suggest that D-alanine influences the neuroendocrine stress response which may then impact on emotion. Aims: The current study explored the effects of D-serine and D-alanine on emotional processing, cognition and the levels of the stress hormone cortisol in healthy volunteers. Methods: In a double-blind, placebo-controlled randomised study, participants (n=63) received a single oral dose of either D-serine, D-alanine (60 mg/kg) or placebo and then performed the Emotional Test Battery and N-back task (two hours post-administration) and provided saliva samples at fixed intervals. Results: Subjects administered with D-alanine were faster at identifying facial expressions of fear, surprise and anger, and at categorising negative self-referential words. Participants on D-alanine also showed a trend to recall more words than placebo in a memory task. D-serine did not have any meaningful effects in any of the tasks. Neither amino acid had a significant effect on salivary cortisol or working memory. Conclusion: This study is the first to suggest that D-alanine can modulate emotional cognitive processing after a single dose. The lack of findings for D-serine nevertheless contrasts a previous study, emphasising a need for further investigation to clarify discrepancies. A better understanding of the physiological actions of D-amino acids would be beneficial in evaluating their therapeutic potential.
Monoubiquitination by the human Fanconi anemia core complex clamps FANCI:FANCD2 on DNA in filamentous arrays

FANCI:FANCD2 monoubiquitination is a critical event for replication fork stabilization by the Fanconi anemia (FA) DNA repair pathway. It has been proposed that at stalled replication forks, monoubiquitinated-FANCD2 serves to recruit DNA repair proteins that contain ubiquitin-binding motifs. Here, we have reconstituted the FA pathway in vitro to study functional consequences of FANCI:FANCD2 monoubiquitination. We report that monoubiquitination does not promote any specific exogenous protein:protein interactions, but instead stabilizes FANCI:FANCD2 heterodimers on dsDNA. This clamping requires monoubiquitination of only the FANCD2 subunit. We further show using electron microscopy that purified monoubiquitinated FANCI:FANCD2 forms filament-like arrays on long dsDNA. Our results reveal how monoubiquitinated FANCI:FANCD2, defective in many cancer types and all cases of FA, is activated upon DNA binding.
Elevated Labile Iron Levels in CD4 and CD8 T Cells From HIV Positive Individuals With Undetectable Viral Load.

Iron is a key factor at various stages of HIV life cycle and determines the progression of HIV infection. Data about labile cellular iron pool (LIP) in the settings of cART are lacking. Yet LIP is directly related to the generation of reactive oxygen species (ROS), and may contribute to immune activation, dysfunction and exhaustion. Using multiparameter flow cytometry, we evaluated LIP in CD4 and CD8 T-cells from HIV+ patients with sustained viral suppression (SVS) as a result of continuous long-term cART. Based on the recovery of CD4/CD8 ratio two patients' subgroups were defined: A(n=26), CD4/CD8>0.9 and B(n=37), CD4/CD8<0.9, with significantly differing CD4AC (mean 752vs.571 cells/µl, p<0.05). While hemoglobin (Hb) and serum iron (sFe) had recovered in all patients, CD4 and CD8 T cell LIP were significantly higher as compared to controls, both in the subgroup with complete (A) and with incomplete (B) immune recovery (mean CD4ΔMFI 318.7 and 777.8 vs.157.6; mean CD8ΔMFI 359.5 and 628.7vs.179.2,ANOVA p<0.05 for both). CD4 LIP correlated inversely with CD4AC (R= -0.4, p <0.01), and both CD4 and CD8 LIP - with CD4/CD8 ratio (R=-0.4, p<0.01). Thus, increased CD4 and CD8 T cell LIP in the settings of SVS and immune recovery is a sensitive marker of residual immune activation and may predict immune exhaustion in long-term cART-treated patients.
Effects of different adhesion promoters and deproteinizing agents on the shear bond strength of orthodontic brackets: An in vitro study

OBJECTIVE: To evaluate the effects of different adhesion promoters, namely, Enhance LC, Ortho Solo, Assure Universal Bonding Resin and deproteinizing agents such as 5.25% NaOCl, 10% papain gel on the shear bond strength of orthodontic brackets. MATERIALS AND METHOD: The present study was approved by the Ethics Committee of Teerthanker Mahaveer Dental College and Research Centre, affiliated to Teerthanker Mahaveer University, Moradabad, India. Around 150 extracted sound human upper bicuspids were taken and divided into six groups. Group 1 control (37% H3PO4), Group 2 (37% H3PO4+ Ortho Solo), Group 3 (37% H3PO4+ Assure Universal Bonding Resin), Group 4 (37% H3PO4+ Enhance LC), Group 5 (5.25% NaOCl + 37% H3PO4), and Group 6 (10% papain gel + 37% H3PO4). In all the groups (n = 150) orthodontic metal brackets were bonded with TransbondTM XT and all the samples were subjected for evaluation of shear bond strength using Instron universal testing machine at a cross speed of 0.5 mm/min. The bracket failure mode was examined using Adhesive Remnant Index (ARI). The Kruskal-Wallis test and the Mann-Whitney test were used to compare the shear bond strength. The Chi-square test was used to determine significant differences in the ARI scores among the groups. The significance for all statistical tests was P < 0.05. RESULTS: Mean values of shear bond strength showed statistically significant differences between the evaluated groups (P < 0.005). The lowest and highest shear bond strength was attributed to Group 1 (control) and Group 2 (Ortho Solo), respectively. No statistically significant difference was noted for the mean ARI scores between control, adhesion promoters, and deproteinized group (P < 0.05). CONCLUSION: It was concluded that adhesion promoters and deproteinizing agents can be used to enhance the shear bond strength of orthodontic brackets. Among all the groups Ortho Solo showed the highest bond strength when used with TransbondTM XT.