Background. Parkinson's disease (PD) is the second most commonly neurodegenerative disease after Alzheimer's disease which occurs to nearly 1% of the population > 50 years old. Inflammatory and bone biomarkers have both become valuable tools for PD diagnosis and prognosis. However, no studies have examined these markers in Saudi patients diagnosed with PD. Objectives. To assess the biomarkers and proinflammatory cytokines from blood with PD in serum. Methods. In our study, we included 26 patients with PD and 24 controls. Blood samples were withdrawn from subjects with PD and their matched controls. Biomarkers multiplex assay from Milliplex was used to assess the levels of IL-1B, IL-6, TNF-α, osteoprotegerin (OPG), osteopontin (OPN), and PTH (parathyroid hormone). Data was analyzed using the Statistical Package, GraphPad Prism. Results. We found that IL-1ß cytokine is significantly higher in patients with PD (p value = 0.0014). However, there are no statistically significant variances found among the two studied groups with regard to the IL-6 and TNF-α cytokines levels. We also found that levels of PTH are decreased in the PD subjects than the age-matched controls (p value= 0.003). Also, the bone matrix glycoproteins, including osteoprotegerin (OPG) and osteopontin (OPN), are significantly upregulated (p value= 0.04 for OPG and p value= 0.003 for OPN), as compared to the controls. Conclusions. Our findings are reliable with the possibility that inflammatory and bone markers can be used as biomarkers in PD prognosis. However, to clarify the natural role and consequence of these markers in PD pathology, further larger cohort studies are needed.

Double-row transosseous-equivalent (TOE) rotator cuff repair techniques have been widely accepted because of their superior biomechanical properties when compared with arthroscopic single-row repair. Concerns regarding repair overtensioning with medial-row knot tying have led to increased interest in knotless repair techniques; however, there is a paucity of clinical data to guide the choice of technique.

Injuries continue to rise among youth baseball players despite extensive research into prevention and the availability of throwing guidelines such as Pitch Smart. More research is needed to understand whether adherence to the current guidelines decreases injuries.

The Patient-Reported Outcomes Measurement Information System (PROMIS) was developed to capture patient-reported outcomes (PROs) in an efficient manner. Few studies have assessed this instrument postoperatively.

Persons with HIV infection (PWH) have increased risk for cardiovascular disease (CVD), but the underlying mechanisms remain unclear. Coronary thrombosis is known to provoke myocardial infarctions, but whether PWH have elevated thrombotic propensity is unknown. We compared thrombogenicity of PWH on antiretroviral therapy versus matched controls using the Badimon chamber. Measures of inflammation, platelet reactivity, and innate immune activation were simultaneously performed. Enrolled PWH were then randomized to placebo, aspirin (81 mg), or clopidogrel (75 mg) for 24 weeks to assess treatment effects on study parameters. Thrombogenicity was significantly higher in PWH and correlated strongly with plasma levels of D-dimer, soluble TNF receptors 1 and 2, and circulating classical and nonclassical monocytes in PWH. Clopidogrel significantly reduced thrombogenicity and sCD14. Our data suggest that higher thrombogenicity, interacting with inflammatory and immune activation markers, contributes to the increased CVD risk observed in PWH. Clopidogrel exhibits an anti-inflammatory activity in addition to its antithrombotic effect in PWH.

In a study by Murray and Lohman (M&L), the authors suggest that remote sensing data are useful for monitoring land subsidence due to aquifer system compaction. We agree. To infer aquifer dynamics, we provide a more detailed and joint analysis of deformation and groundwater data. Investigating well data in the Tulare Basin, we find that groundwater levels stabilized before 2015 and show that M&L's observed continued subsidence through July 2016 is likely caused by the delayed compaction of the aquitard. Our analysis suggests the observed 2017 transient uplift is not due to recharge of the aquifer system after heavy winter rainfall because it requires an unrealistic vertical hydraulic gradient nearly five orders of magnitude larger than that typical of Tulare Basin. We find that, regardless of the amount of rainfall, transient annual uplifts of ~3 cm occur in May to June. Using an elastic skeletal storage coefficient of 5 × 10-3, we link this ground uplift to annual groundwater level changes.

Cannabis is one of the oldest cultivated plants in East Asia, grown for grain and fiber as well as for recreational, medical, and ritual purposes. It is one of the most widely used psychoactive drugs in the world today, but little is known about its early psychoactive use or when plants under cultivation evolved the phenotypical trait of increased specialized compound production. The archaeological evidence for ritualized consumption of cannabis is limited and contentious. Here, we present some of the earliest directly dated and scientifically verified evidence for ritual cannabis smoking. This phytochemical analysis indicates that cannabis plants were burned in wooden braziers during mortuary ceremonies at the Jirzankal Cemetery (ca. 500 BCE) in the eastern Pamirs region. This suggests cannabis was smoked as part of ritual and/or religious activities in western China by at least 2500 years ago and that the cannabis plants produced high levels of psychoactive compounds.

Mild hearing and visual difficulties are common in childhood, and both may have implications for educational achievement. However, the impact of co-occurring common hearing and visual difficulties in childhood is not known.

Chronic fatigue syndromemyalgic encephalomyelitis (CFS/ME) is relatively common among children and adolescents; however, little is known about the physical activity levels and patterns of this population. The aim of this study was to examine the underlying patterns of physical activity among youth with mild-to-moderate CFS/ME. Cross-sectional associations between physical activity patterns with self-reported physical function, pain, fatigue, anxiety and depression were also examined.

Adolescent idiopathic scoliosis (AIS) is one of the most common structural spinal deformities in adolescents, becoming apparent around the time of puberty. Schroth scoliosis-specific exercises have demonstrated promising results in reducing the progression of AIS.

Temporal lobe epilepsy (TLE) is a chronic disease, characterized by severe and refractory seizures, triggered in the hippocampus and/or amygdala, disrupting the blood-brain barrier. This disruption can sustain, or aggravate, the epileptic condition. The aim of this study was to evaluate the activation of the kallikrein-kinin system in patients with TLE, as it relates to the maintenance of blood-brain barrier. Human hippocampal sclerotic tissues removed after surgery for seizure control, plasma, and serum were used in the following assays: immunostaining for white blood cells in the TLE hippocampus, C-reactive protein in serum, quantification of plasma kallikrein (PKal) and cathepsin B (CatB) activity in serum and plasma, quantification of C1-inhibitor, analysis of high-molecular-weight kininogen (H-kininogen) fragments, and activation of plasma prekallikrein for comparison with healthy controls. Infiltration of white blood cells in the sclerotic hippocampus and a significant increase in the neutrophil/lymphocyte ratio in the blood of TLE patients were observed. High levels of C-reactive protein (TLE = 1.4 ± 0.3 µg/mL), PKal (TLE = 5.4 ± 0.4 U/mL), and CatB (TLE = 4.9 ± 0.4 U/mL) were also evident in the serum of TLE patients comparing to controls. A strong linear correlation was observed between active CatB and PKal in the serum of TLE patients (r = 0.88). High levels of cleaved H-kininogen and free PKal, and low levels of C1-inhibitor (TLE = 188 ± 12 µg/mL) were observed in the serum of TLE patients. Our data demonstrated that the plasma kallikrein-kinin system is activated in patients with TLE. OPEN SCIENCE BADGES: This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.

Chronic pain is an unmet clinical problem with vast individual, societal, and economic impact. Pathologic activity of the peripheral somatosensory afferents is one of the major drivers of chronic pain. This overexcitable state of somatosensory neurons is, in part, produced by the dysregulation of genes controlling neuronal excitability. Despite intense research, a unifying theory behind neuropathic remodelling is lacking. Here, we show that transcriptional suppressor, repressor element 1-silencing transcription factor (REST; neuron-restrictive silencing factor, NRSF), is necessary and sufficient for the development of hyperalgesic state after chronic nerve injury or inflammation. Viral overexpression of REST in mouse dorsal root ganglion (DRG) induced prominent mechanical and thermal hyperalgesia in vivo. Sensory neuron-specific, inducible Rest knockout prevented the development of such hyperalgesic state in 3 different chronic pain models. Genetic deletion of Rest reverted injury-induced hyperalgesia. Moreover, viral overexpression of REST in the same neurons in which its gene has been genetically deleted restored neuropathic hyperalgesia. Finally, sensory neuron specific Rest knockout prevented injury-induced downregulation of REST target genes in DRG neurons. This work identified REST as a major regulator of peripheral somatosensory neuron remodelling leading to chronic pain. The findings might help to develop a novel therapeutic approache to combat chronic pain.

Identifying and eliminating snail habitats is the key measure for schistosomiasis control, critical for the nationwide strategy of eliminating schistosomiasis in China. Here, our aim was to construct a new analytical framework to predict high-risk snail habitats based on a large sample field survey for Oncomelania hupensis, providing guidance for schistosomiasis control and prevention.

Escherichia coli represents a classical intestinal gram-negative commensal. Despite this commensalism, different E. coli strains can mediate disparate immunogenic properties in a given host. Symbiotic E. coli strains such as E. coli Nissle 1917 (EcN) are attributed beneficial properties, e.g., promotion of intestinal homeostasis. Therefore, we aimed to identify molecular features derived from symbiotic bacteria that might help to develop innovative therapeutic alternatives for the treatment of intestinal immune disorders. This study was performed using the dextran sodium sulphate (DSS)-induced colitis mouse model, which is routinely used to evaluate potential therapeutics for the treatment of Inflammatory Bowel Diseases (IBDs). We focused on the analysis of flagellin structures of different E. coli strains. EcN flagellin was found to harbor a substantially longer hypervariable region (HVR) compared to other commensal E. coli strains, and this longer HVR mediated symbiotic properties through stronger activation of Toll-like receptor (TLR)5, thereby resulting in interleukin (IL)-22-mediated protection of mice against DSS-induced colitis. Furthermore, using bone-marrow-chimeric mice (BMCM), CD11c+ cells of the colonic lamina propria (LP) were identified as the main mediators of these flagellin-induced symbiotic effects. We propose flagellin from symbiotic E. coli strains as a potential therapeutic to restore intestinal immune homeostasis, e.g., for the treatment of IBD patients.

Motion triggered camera traps are an increasingly popular tool for wildlife research and can be used to survey for multiple species simultaneously. As with all survey techniques, it is crucial to conduct camera trapping research following study designs that include adequate spatial and temporal replication, and sufficient probability of detecting species presence. The use and configuration of multiple camera traps within a single survey site are understudied considerations that could have a substantial impact on detection probability. Our objective was to test the role that camera number (one, two or three units), and spacing along a linear transect (100 m or 150 m), have on the probability of detecting a species given it is present. From January to March, 2017 we collected data on six mammal species in Maine, USA: coyote (Canis latrans), fisher (Pekania pennanti), American marten (Martes americana), short-tailed weasel (Mustela erminea), snowshoe hare (Lepus americanus), and American red squirrel (Tamiasciurus hudsonicus). We used multi-scale occupancy modelling to compare pooled detection histories of different configuration of five cameras deployed at the same survey site (n = 32), and how the configuration would influence the probability of detecting a species given it was available at the site. Across all six species, we found substantial increases in probability of detection as the number of cameras increased from one to two (22 to 400 percent increase), regardless of the spacing between cameras. For most species the magnitude of the increase was less substantial when adding a third camera (4 to 85 percent increase), with coyote and snowshoe hare showing a pronounced effect. The influence of survey station features also varied by species. We suggest that using pooled data from two or three cameras at a survey site is a cost effective approach to increase detection success over a single camera.

Freely-available satellite data streams and the ability to process these data on cloud-computing platforms such as Google Earth Engine have made frequent, large-scale landcover mapping at high resolution a real possibility. In this paper we apply these technologies, along with machine learning, to the mapping of peatlands-a landcover class that is critical for preserving biodiversity, helping to address climate change impacts, and providing ecosystem services, e.g., carbon storage-in the Boreal Forest Natural Region of Alberta, Canada. We outline a data-driven, scientific framework that: compiles large amounts of Earth observation data sets (radar, optical, and LiDAR); examines the extracted variables for suitability in peatland modelling; optimizes model parameterization; and finally, predicts peatland occurrence across a large boreal area (397, 958 km2) of Alberta at 10 m spatial resolution (equalling 3.9 billion pixels across Alberta). The resulting peatland occurrence model shows an accuracy of 87% and a kappa statistic of 0.57 when compared to our validation data set. Differentiating peatlands from mineral wetlands achieved an accuracy of 69% and kappa statistic of 0.37. This data-driven approach is applicable at large geopolitical scales (e.g., provincial, national) for wetland and landcover inventories that support long-term, responsible resource management.

The MYC gene encodes a human transcription factor and proto-oncogene that is dysregulated in over half of all known cancers. To better understand potential post-transcriptional regulatory features affecting MYC expression, we analyzed secondary structures in the MYC mRNA using a program that is optimized for finding small locally-folded motifs with a high propensity for function. This was accomplished by calculating folding metrics across the MYC sequence using a sliding analysis window and generating unique consensus base pairing models weighted by their lower-than-random predicted folding energy. A series of 30 motifs were identified, primarily in the 5' and 3' untranslated regions, which show evidence of structural conservation and compensating mutations across vertebrate MYC homologs. This analysis was able to recapitulate known elements found within an internal ribosomal entry site, as well as discover a novel element in the 3' UTR that is unusually stable and conserved. This novel motif was shown to affect MYC expression, potentially via the modulation of miRNA target accessibility or other trans-regulatory factors. In addition to providing basic insights into mechanisms that regulate MYC expression, this study provides numerous, potentially druggable RNA targets for the MYC gene, which is considered "undruggable" at the protein level.

The relationship between noncoding DNA sequence and gene expression is not well-understood. Massively parallel reporter assays (MPRAs), which quantify the regulatory activity of large libraries of DNA sequences in parallel, are a powerful approach to characterize this relationship. We present MPRA-DragoNN, a convolutional neural network (CNN)-based framework to predict and interpret the regulatory activity of DNA sequences as measured by MPRAs. While our method is generally applicable to a variety of MPRA designs, here we trained our model on the Sharpr-MPRA dataset that measures the activity of ∼500,000 constructs tiling 15,720 regulatory regions in human K562 and HepG2 cell lines. MPRA-DragoNN predictions were moderately correlated (Spearman ρ = 0.28) with measured activity and were within range of replicate concordance of the assay. State-of-the-art model interpretation methods revealed high-resolution predictive regulatory sequence features that overlapped transcription factor (TF) binding motifs. We used the model to investigate the cell type and chromatin state preferences of predictive TF motifs. We explored the ability of our model to predict the allelic effects of regulatory variants in an independent MPRA experiment and fine map putative functional SNPs in loci associated with lipid traits. Our results suggest that interpretable deep learning models trained on MPRA data have the potential to reveal meaningful patterns in regulatory DNA sequences and prioritize regulatory genetic variants, especially as larger, higher-quality datasets are produced.

More than 2.5 million newborns die each year, accounting for 47% of children dying worldwide before their age of five years. Complications of preterm birth are the leading cause of death among newborns. Pakistan is amongst the top ten countries with highest preterm birth rate per 1000 live births. Globally, Every Newborn Action Plan (ENAP) has emphasized on Kangaroo Mother Care (KMC) as an essential component of neonatal health initiatives.

In contrast to human cells, very few HSV-1 genes are known to be spliced, although the same pre-mRNA processing machinery is shared. Here, through global analysis of splice junctions in cells infected with HSV-1 and an HSV-1 mutant virus with deletion of infectious cell culture protein 27 (ICP27), one of two viral immediate early (IE) genes essential for viral replication, we identify hundreds of novel alternative splice junctions mapping to both previously known HSV-1 spliced genes and previously unknown spliced genes, the majority of which alter the coding potential of viral genes. Quantitative and qualitative splicing efficiency analysis of these novel alternatively spliced genes based on RNA-Seq and RT-PCR reveals that splicing at these novel splice sites is efficient only when ICP27 is absent; while in wildtype HSV-1 infected cells, the splicing of these novel splice junctions is largely silenced in a gene/sequence specific manner, suggesting that ICP27 not only promotes accumulation of ICP27 targeted transcripts but also ensures correctness of the functional coding sequences through inhibition of alternative splicing. Furthermore, ICP27 toggles expression of ICP34.5, the major viral neurovirulence factor, through inhibition of splicing and activation of a proximal polyadenylation signal (PAS) in the newly identified intron, revealing a novel regulatory mechanism for expression of a viral gene. Thus, through the viral IE protein ICP27, HSV-1 co-opts both splicing and polyadenylation machinery to achieve optimal viral gene expression during lytic infection. On the other hand, during latent infection when ICP27 is absent, HSV-1 likely takes advantages of host splicing machinery to restrict expression of randomly activated antigenic viral genes to achieve immune evasion.