Bioinformatics-Based Identification of Expanded Repeats: A Non-reference Intronic Pentamer Expansion in RFC1 Causes CANVAS

Genomic technologies such as next-generation sequencing (NGS) are revolutionizing molecular diagnostics and clinical medicine. However, these approaches have proven inefficient at identifying pathogenic repeat expansions. Here, we apply a collection of bioinformatics tools that can be utilized to identify either known or novel expanded repeat sequences in NGS data. We performed genetic studies of a cohort of 35 individuals from 22 families with a clinical diagnosis of cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome (CANVAS). Analysis of whole-genome sequence (WGS) data with five independent algorithms identified a recessively inherited intronic repeat expansion [(AAGGG)exp] in the gene encoding Replication Factor C1 (RFC1). This motif, not reported in the reference sequence, localized to an Alu element and replaced the reference (AAAAG)11 short tandem repeat. Genetic analyses confirmed the pathogenic expansion in 18 of 22 CANVAS-affected families and identified a core ancestral haplotype, estimated to have arisen in Europe more than twenty-five thousand years ago. WGS of the four RFC1-negative CANVAS-affected families identified plausible variants in three, with genomic re-diagnosis of SCA3, spastic ataxia of the Charlevoix-Saguenay type, and SCA45. This study identified the genetic basis of CANVAS and demonstrated that these improved bioinformatics tools increase the diagnostic utility of WGS to determine the genetic basis of a heterogeneous group of clinically overlapping neurogenetic disorders

Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice

IMPORTANCE: It is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes. OBJECTIVE: To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a pathogenic/likely pathogenic (P/LP) variant were included in the study. Case report forms were completed by all health care professionals. EXPOSURES: Genetic test results. MAIN OUTCOMES AND MEASURES: Clinical management changes after a genetic diagnosis (ie, 1 P/LP variant in autosomal dominant and X-linked diseases; 2 P/LP variants in autosomal recessive diseases) and subsequent patient outcomes as reported by health care professionals on case report forms. RESULTS: Among 418 patients, median (IQR) age at the time of testing was 4 (1-10) years, with an age range of 0 to 52 years, and 53.8% (n = 225) were female individuals. The mean (SD) time from a genetic test order to case report form completion was 595 (368) days (range, 27-1673 days). A genetic diagnosis was associated with changes in clinical management for 208 patients (49.8%) and usually (81.7% of the time) within 3 months of receiving the result. The most common clinical management changes were the addition of a new medication (78 [21.7%]), the initiation of medication (51 [14.2%]), the referral of a patient to a specialist (48 [13.4%]), vigilance for subclinical or extraneurological disease features (46 [12.8%]), and the cessation of a medication (42 [11.7%]). Among 167 patients with follow-up clinical information available (mean [SD] time, 584 [365] days), 125 (74.9%) reported positive outcomes, 108 (64.7%) reported reduction or elimination of seizures, 37 (22.2%) had decreases in the severity of other clinical signs, and 11 (6.6%) had reduced medication adverse effects. A few patients reported worsening of outcomes, including a decline in their condition (20 [12.0%]), increased seizure frequency (6 [3.6%]), and adverse medication effects (3 [1.8%]). No clinical management changes were reported for 178 patients (42.6%). CONCLUSIONS AND RELEVANCE: Results of this cross-sectional study suggest that genetic testing of individuals with epilepsy may be materially associated with clinical decision-making and improved patient outcomes

Periodic Alternating Nystagmus (PAN) as a Consequence of Ataxia-Telangiectasia

We present a case of Gerstmann-Straussler-Scheinker syndrome (GSS) presenting with vertical-gaze palsy who was initially thought to have spinocerebellar ataxia versus atypical parkinsonism. The few prior reports of eye movement abnormalities in GSS highlight early SWJs, supranuclear vertical gaze palsy, impaired vertical pursuits/OKN, and cerebellar oculomotor abnormalities (1,2). Our case emphasizes that in patients with progressive ataxia and supranuclear gaze palsy, a diagnosis of prion disease should be considered

Magnetic Water Treatment: An Eco-Friendly Irrigation Alternative to Alleviate Salt Stress of Brackish Water in Seed Germination and Early Seedling Growth of Cotton (Gossypium hirsutum L.)

Magnetized water has been a promising approach to improve crop productivity but the conditions for its effectiveness remain contradictory and inconclusive. The objective of this research was to understand the influences of different magnetized water with varying quality on seed absorption, germination, and early growth of cotton. To this end, a series of experiments involving the seed soaking process, germination test, and pot experiment were carried out to study the effects of different qualities (fresh and brackish water) of magnetized water on seed water absorption, germination, seedling growth, photosynthetic characteristics, and biomass of cotton in 2018. The results showed that the maximum relative water absorption of magnetized fresh and magnetized brackish water relatively increased by 16.76% and 19.75%, respectively, and the magnetic effect time of brackish water was longer than fresh water. The relative promotion effect of magnetized brackish water on cotton seed germination and growth potential was greater than magnetized fresh water. The cotton seeds germination rate under magnetized fresh and magnetized brackish water irrigation relatively increased by 13.14% and 41.86%, respectively, and the relative promoting effect of magnetized brackish water on the vitality indexes and the morphological indexes of cotton seedlings was greater than magnetized fresh water. Unlike non-magnetized water, the net photosynthetic rate (Pn), transpiration rate (Tr), and instantaneous water use efficiency (iWUE) of cotton irrigated with magnetized water increased significantly, while the stomatal limit value (Ls) decreased. The influences of photosynthesis and water use efficiency of cotton under magnetized brackish water were greater than magnetized fresh water. Magnetized fresh water had no significant effect on biomass proportional distribution of cotton but magnetized brackish water irrigation markedly improved the root-to-stem ratio of cotton within a 35.72% range. Therefore, the magnetization of brackish water does improve the growth characteristics of cotton seedlings, and the biological effect of magnetized brackish water is more significant than that of fresh water. It is suggested that magnetized brackish water can be used to irrigate cotton seedlings when freshwater resources are insufficient

Experimental Investigation of the Different Polyacrylamide Dosages on Soil Water Movement under Brackish Water Infiltration

The use of soil conditioners in conjunction with brackish water irrigation is critical for the efficient development and use of brackish water as well as the enhancement of the structure of saline soil and stimulating crop growth. This study investigated the effects of different polyacrylamide (PAM) dosages (0, 0.02%, 0.04%, and 0.06%) on the water flow properties of sandy loam during brackish water infiltration using one-dimensional vertical and horizontal soil column infiltration experiments. The results showed that: (1) PAM could lower the soil infiltration rate and increase soil water retention performance under brackish water infiltration conditions. (2) PAM had a significant effect on the parameters of the Philip and Kostiakov infiltration models. The soil sorption rate S and the empirical coefficient λ were the smallest, and the empirical index β was the largest when the PAM dosage was 0.04%. (3) PAM dosage displayed a quadratic polynomial connection with the soil saturated water content and the saturated hydraulic conductivity. The soil saturated water content was highest when the PAM dosage was 0.04%, the intake suction hd of the Brooks-Corey model increased by 15.30%, and the soil water holding capacity was greatly improved. (4) Soil treated with PAM could absorb more water under the same soil water suction, whereas the soil unsaturated hydraulic conductivity and its growth rate decreased. The soil saturated diffusion rate Ds, as well as the soil water diffusion threshold, rose. Finally, the 0.04% PAM dosage could improve soil hydrodynamic characteristics under brackish water infiltration, which is beneficial for the efficient utilization of brackish water

DESIGN AND PERFORMANCE RESEARCH ON FLEXURE MICRO ROTARY MECHANISM WITH STRAIGHT CIRCULAR

The deformation of static bending was analyzed for uniform beam by the boundary element method.Non-uniform beam was combined with multiple uniform beams by method of system rigid combination without coordinate transformation.Stiffness equation of flexure hinges with straight circular was proposed.A micro rotary mechanism with symmetric drive as well as guiding and transformation was designed based on drive and guiding principles of flexure hinges with straight circular,which is able to make linear motion displacement into rotary displacement,the analysis of degree of freedom about it was given.The analysis of statics with micro rotary mechanism was finished by the finite element method,and the analysis results show that the largest simulation stress of the mechanism is much less than the material allowable stress.The dynamics-free-modal with micro rotary mechanism was analyzed by the finite element,and experiment of the modal analysis was finished,the error between the experimental results and the finite element is less than 6.25%,the analysis results prove that the mechanism has a high the First six order natural frequency and it will not cause resonance in the movement process of the precision rotary system with macro /micro dual-drive.The analysis of performance and experiment shows that micro rotary mechanism has the feature of single-degreefreedom-drive and high reliability,as well as good performance of modal

Optimizing the Maize Irrigation Strategy and Yield Prediction under Future Climate Scenarios in the Yellow River Delta

The contradiction between water demand and water supply in the Yellow River Delta restricts the corn yield in the region. It is of great significance to formulate reasonable irrigation strategies to alleviate regional water use and improve corn yield. Based on typical hydrological years (wet year, normal year, and dry year), this study used the coupling model of AquaCrop, the multi-objective genetic algorithm (NSGA-III), and TOPSIS-Entropy established using the Python language to solve the problem, with the objectives of achieving the minimum irrigation water (IW), maximum yield (Y), maximum irrigation water production rate (IWP), and maximum water use efficiency (WUE). TOPSIS-Entropy was then used to make decisions on the Pareto fronts, seeking the best irrigation decision under the multiple objectives. The results show the following: (1) The AquaCrop-OSPy model accurately simulated the maize growth process in the experimental area. The R2 values for canopy coverage (CC) in 2019, 2020, and 2021 were 0.87, 0.90, and 0.92, respectively, and the R2 values for the aboveground biomass (BIO) were 0.97, 0.96, and 0.96. (2) Compared with other irrigation treatments, the rainfall in the test area can meet the water demand of the maize growth period in wet years, and net irrigation can significantly reduce IW and increase Y, IWP, and WUE in normal and dry years. (3) Using LARS-WG (a widely employed stochastic weather generator in agricultural climate impact assessment) to generate future climate scenarios externally resulted in a higher CO2 concentration with increased production and slightly reduced IW demand. (4) Optimizing irrigation strategies is important for allowing decision makers to promote the sustainable utilization of water resources in the study region and increase maize crop yields

Effect of Drip Irrigation, N, K, and Zn Coupling on <inline-formula><math display="inline"><semantics><mrow><mi>P</mi><mi>n</mi></mrow></semantics></math></inline-formula> of Densely Cultivated Apple on Dwarf Rootstock in Xinjiang, China

This study aimed to determine the effect of irrigation amount (W), nitrogen (N), potassium (K), and zinc (Zn) on the net photosynthetic rate (Pn) of closely planted apple trees on dwarf rootstocks in arid areas of Xinjiang. Taking the “Royal Gala” apple as the experimental material, a mathematical model for Pn was established using the principle of four-factor five-level quadratic regression with a general rotation combination design. The results show that: (1) The regression equations reached significant levels (F = 37.06 > F0.01(11.11) = 4.54). (2) The effect of W, N, K, Zn on Pn is significant with relative importance W > N > Zn > K. (3) The results of single factor analysis showed that with an increase in W, N, K, and Zn, Pn exhibits an n-shaped parabolic response. (4) The positive coupling between W and N is significant, and the positive coupling between W and Zn is also significant. (5) Analysis of the interaction between sets of three factors revealed that W, N, and Zn could be combined to best effect, with the maximum value reaching 12.77 μmol·m−2·s−1. Compared with W×K×Zn and W×N×K, the combination of W×N×Zn reduces W by 9.2% and 6.3%, respectively, which indicates its suitability for use in the dry and water deficient planting environment in Xinjiang. (6) Within the 95% confidence level, when W is 258–294.75 mm, N is 33.44–39.51 kg/hm2, K is 53.82–69.39 kg/hm2, and Zn is 6.46–7.84 kg/hm2, the net photosynthetic rate reaches 11 μmol·m−2·s−1

Teaching the &quot;Family History&quot; Through Group Reflection

Background: Family health history (FH) is a useful tool for assessing health risk and improving communication among family members, but remains underutilized in primary care practice. The goals of this study were to assess the utility of a content-driven group reflection on family history on student learning, and to equip them with tools to improve their skills in FH assessment. Methods: A 90-minute pilot Family History and Communication Reflection module was developed and made available to first and second-year medical students completing a longitudinal ambulatory clerkship; a group reflection model was used. 16 students (13% of the first year class) participated and 8 students completed the evaluation form. Results: The majority of students were satisfied with the module, would recommend the module to another student, and felt prepared or very prepared to incorporate FH assessment tools into their clinical practice. Conclusions: The pilot FH module was well-received by first-year medical students as a strategy for emphasizing the importance of assessing FH in a busy primary care setting and providing practical tools for FH. The reflective learning approach was cited as helpful for using and building upon prior clerkship experience. Family health history (FH) continues to be an important factor for understanding a patient&apos;s risk fo