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Abstract Background The growing body of research on kidney disease in children has identified a broad spectrum of genetic etiologies. Methods We conducted a prospective study to evaluate the efficacy of an optimized genetic test and subclinical changes in a real-world context before kidney transplantation. All cases involved recipients under the age of 18 who underwent whole exome sequencing (ES) between 2013 and 2022. Results The study population included 244 children, with a median age of 13.1 years at transplantation. ES provided a molecular genetic diagnosis in 114 (46.7%) probands with monogenic variants in 15 known disease-causing genes. ES confirmed the suspected clinical diagnosis in 74/244 (30.3%) cases and revised the pre-exome clinical diagnoses in 40/244 (16.4%) cases. ES also established a specific underlying cause for kidney failure for 19 patients who had previously had an unknown etiology. Genetic diagnosis influenced clinical management in 88 recipients (36.1%), facilitated genetic counseling for 18 families (7.4%), and enabled comprehensive assessment of living donor candidates in 35 cases (14.3%). Conclusions Genetic diagnosis provides critical insights into the pathogenesis of kidney disease, optimizes clinical strategies concerning risk assessment of living donors, and enhances disease surveillance of recipients.

Abstract Background Partner support is associated with better weight loss outcomes in observational studies, but randomized trials show mixed results for including partners. Unclear is whether teaching communication skills to couples will improve weight loss in a person attempting weight loss (index participant). Purpose To compare the efficacy of a partner-assisted intervention versus participant-only weight management program on 24-month weight loss. Methods This community-based study took place in Madison, WI. Index participants were eligible if they met obesity guideline criteria to receive weight loss counseling, were aged 18–74 years, lived with a partner, and had no medical contraindications to weight loss; partners were aged 18–74 years and not underweight. Couples were randomized 1:1 to a partner-assisted or participant-only intervention. Index participants in both arms received an evidence-based weight management program. In the partner-assisted arm, partners attended half of the intervention sessions, and couples were trained in communication skills. The primary outcome was index participant weight at 24 months, assessed by masked personnel; secondary outcomes were 24-month self-reported caloric intake and average daily steps assessed by an activity tracker. General linear mixed models were used to compare group differences in these outcomes following intent-to-treat principles. Results Among couples assigned to partner-assisted (n = 115) or participant-only intervention (n = 116), most index participants identified as female (67%) and non-Hispanic White (87%). Average baseline age was 47.27 years (SD 11.51 years) and weight was 106.55 kg (SD 19.41 kg). The estimated mean 24-month weight loss was similar in the partner-assisted (2.66 kg) and participant-only arms (2.89 kg) (estimated mean difference, 0.23 kg [95% CI, -1.58, 2.04 kg], p=0.80). There were no differences in 24-month average daily caloric intake (estimated mean difference 50 cal [95% CI: -233, 132 cal], p=0.59) or steps (estimated mean difference 806 steps [95% CI: -1675, 64 steps], p=0.07). The percentage of participants reporting an adverse event with at least possible attribution to the intervention did not differ by arm (partner-assisted: 9%, participant-only, 3%, p = 0.11). Conclusions Partner-assisted and individual weight management interventions led to similar outcomes in index participants. Trial registration Clinicaltrials.gov NCT03801174, January 11, 2019.

Objective The reported date in the repeat surgical intervention for adolescent lumbar disc herniation (ALDH) after percutaneous endoscopic lumbar discectomy (PELD) was quite scarce. This study aims to introduce cases of repeat surgeries after PELD for ALDH and assess the incidence, chief causes, repeat surgery methods, and surgical outcomes of repeat surgeries after PELD for ALDH. Methods A retrospective multicenter observational study was conducted on patients undergoing repeat surgeries after PELD for ALDH at four tertiary referral hospitals from January 2014 through August 2022. The incidence of repeat surgeries, chief causes, strategies for repeat surgeries, and timing of repeat surgeries were recorded and analyzed. The clinical outcomes were evaluated by the Numeric Rating Scales (NRS) scores and the modified MacNab criteria. Statistical analyses were performed with the Wilcoxon signed‐rank test. Results A total of 23 patients who underwent repeat surgeries after PELD for ALDH were included. The chief causes were re‐herniation (homo‐lateral re‐herniation at the same level, new disc herniation of adjacent level). The repeat surgery methods were revision PELD, micro‐endoscopic discectomy (MED), open discectomy and instrumented lumbar inter‐body fusion. The NRS scores decreased significantly in follow‐up evaluations and these scores demonstrated significant improvement at the last follow‐up (p

Abstract Objective Existing behavioral weight management interventions produce clinically meaningful weight loss. The onset of the COVID‐19 pandemic led to the quick transition of such interventions from in‐person to virtual platforms. This provided a unique opportunity to compare engagement and outcomes for an in‐person versus virtually delivered weight management intervention. Methods A non‐randomized comparison of engagement and weight outcomes was performed between two cohorts who participated in a weight management intervention in person (N = 97) versus three who participated virtually via videoconference (N = 134). Various metrics of engagement were examined, including group class and individual phone call attendance and duration, and retention for weight assessments. Behavioral targets of daily caloric intake and step‐counts and the clinical weight outcome were explored. Results Cohorts (mean [standard deviation] age 47.3 (11.5), 67.1% women: 86.8% White) that participated virtually attended more group sessions (p

Purpose To evaluate the safety and efficacy of performing histotripsy through overlying gas-filled bowel in an ex vivo swine model.Methods An ex vivo model was created to simulate histotripsy treatment of solid organs through gas-filled bowel. Spherical 2.5 cm histotripsy treatments were performed in agar phantoms for each of five treatment groups: 1) control with no overlying bowel (n = 6), 2) bowel 0 cm above phantom (n = 6), 3) bowel 1 cm above phantom (n = 6), 4) bowel 2 cm above phantom (n = 6), and 5) bowel 0 cm above the phantom with increased treatment amplitude (n = 6). Bowel was inspected for gross and microscopic damage, and treatment zones were measured. A ray-tracing simulation estimated the percentage of therapeutic beam path blockage by bowel in each scenario.Results All histotripsy treatments through partial blockage were successful (24/24). No visible or microscopic damage was observed to intervening bowel. Partial blockage resulted in a small increase in treatment volume compared to controls (p = 0.002 and p = 0.036 for groups with bowel 0 cm above the phantom, p > 0.3 for bowel 1 cm and 2 cm above the phantom). Gas-filled bowel was estimated to have blocked 49.6%, 35.0%, and 27.3% of the therapeutic beam at 0, 1, and 2 cm, respectively.Conclusion Histotripsy has the potential to be applied through partial gas blockage of the therapeutic beam path, as shown by this ex vivo small bowel model. Further work in an in vivo survival model appears indicated.

Sclerotinia sclerotiorum (Ss) is one of the most devastating fungal pathogens, causing huge yield loss in multiple economically important crops including oilseed rape. Plant resistance to Ss pertains to quantitative disease resistance (QDR) controlled by multiple minor genes. Genome-wide identification of genes involved in QDR to Ss is yet to be conducted. In this study, we integrated several assays including genome-wide association study (GWAS), multi-omics co-localization, and machine learning prediction to identify, on a genome-wide scale, genes involved in the oilseed rape QDR to Ss. Employing GWAS and multi-omics co-localization, we identified seven resistance-associated loci (RALs) associated with oilseed rape resistance to Ss. Furthermore, we developed a machine learning algorithm and named it Integrative Multi-Omics Analysis and Machine Learning for Target Gene Prediction (iMAP), which integrates multi-omics data to rapidly predict disease resistance-related genes within a broad chromosomal region. Through iMAP based on the identified RALs, we revealed multiple calcium signaling genes related to the QDR to Ss. Population-level analysis of selective sweeps and haplotypes of variants confirmed the positive selection of the predicted calcium signaling genes during evolution. Overall, this study has developed an algorithm that integrates multi-omics data and machine learning methods, providing a powerful tool for predicting target genes associated with specific traits. Furthermore, it makes a basis for further understanding the role and mechanisms of calcium signaling genes in the QDR to Ss.

[This corrects the article DOI: 10.1371/journal.pone.0217185.].

ObjectiveTo describe unilateral transforaminal lumbar interbody fusion (TLIF) via a modified hemilateral spinous process-splitting (MHSPS) approach and determine its effectiveness.MethodsSixty-five consecutive patients with the lumbar degenerative disease who underwent MHSPS TLIF between August 2020 and July 2021 were retrospectively analyzed. Japanese Orthopedic Association (JOA) score and visual analog scale (VAS) scores for back and leg pain were evaluated before surgery and at the last follow-up. Postoperative paraspinal muscle atrophy was evaluated on axial T2-weighted magnetic resonance imaging.ResultsMean JOA score increased from 13.6 ± 3.21 before surgery to 24.72 ± 3.34 at last follow-up (p

Abstract Noninvasive prenatal diagnosis (NIPD) aims to detect fetal-related genetic disorders before birth by detecting markers in the peripheral blood of pregnant women, holding the potential in reducing the risk of fetal birth defects. Fetal-nucleated red blood cells (fNRBCs) can be used as biomarkers for NIPD, given their remarkable nature of carrying the entire genetic information of the fetus. Here, we review recent advances in NIPD technologies based on the isolation and analysis of fNRBCs. Conventional cell separation methods rely primarily on physical properties and surface antigens of fNRBCs, such as density gradient centrifugation, fluorescence-activated cell sorting, and magnetic-activated cell sorting. Due to the limitations of sensitivity and purity in Conventional methods, separation techniques based on micro-/nanomaterials have been developed as novel methods for isolating and enriching fNRBCs. We also discuss emerging methods based on microfluidic chips and nanostructured substrates for static and dynamic isolation of fNRBCs. Additionally, we introduce the identification techniques of fNRBCs and address the potential clinical diagnostic values of fNRBCs. Finally, we highlight the challenges and the future directions of fNRBCs as treatment guidelines in NIPD. Graphical Abstract

Abstract Background Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL; OMIM# 615381) is a rare autosomal dominant disorder, with only a few reported cases worldwide. Herein, we describe the clinical features and underlying molecular etiology of MDPL syndrome in an 8-year-old Chinese patient. Methods We performed otological, endocrine, ultrasound, and radiological examinations, as well as genetic testing. Additionally, the literature concerning MDPL was reviewed to do a retrospective analysis of the pathogenesis, genotype–phenotype correlation, and clinical management. Results The proband was diagnosed with MDPL, presenting with mandibular hypoplasia, a characteristic facial appearance, lipodystrophy, and sensorineural hearing loss (SNHL). Whole-exome sequencing and bioinformatics analysis revealed a de novo missense variant in the POLD1 gene, NM_002691.4:c.3185A>G (NP_002682.2:p.(Gln1062Arg)). The retrospective analysis showed wide variation in the MDPL phenotype, but the most frequent features included mandibular hypoplasia, characteristic facial appearance, lipodystrophy, and SNHL. Conclusions This study supplements the mutational spectrum of POLD1. The genetic analysis contributes to the diagnosis of syndromic deafness, and it has a vital role in clinical management and future genetic consultation.

Satellite radiance data can provide effective initial state for numerical weather prediction models， and the satellite observation including the atmospheric humidity information can solve the problems of the horizontal space limitation and the low detection accuracy on the middle and upper levels of the conventional water vapor detection.By using the three-dimensional variational assimilation method， the study of assimilating Microwave Humidity Sounder-2 （MWHS-2） data from FY-3C polar orbiting satellite was constructed based on the Rapid refresh Multi-scale Analysis and Prediction System-Short-term （RMAPS-ST） developed by Beijing Institute of Urban Meteorology.On this basis， 3-hour cycle assimilation numerical simulation experiments in the 0~24 h forecast period were carried out in late July 2019 for a total of 12 days， and the influence of FY-3C Microwave Humidity Sounder-2 data assimilation on the prediction of RMAPS-ST was evaluated.The results show that， the statistical characteristic of the deviation between the observed and the simulated brightness temperature is closer to the Gaussian distribution with zero mean value after the quality control and deviation correction， and the standard deviation is reduced， which will effectively improve the adjustment of MWHS-2 radiance to the analysis field.The prediction results of preliminary assimilation of MWHS-2 radiance in RMAPS-ST system are verified and evaluated by using conventional observation data.The results show that The average bias and the root mean square error of the specific humidity at hours 6， 12 and 18 of the forecasts below 400 hPa is decreased with satellite radiance assimilation.Further more， assimilation experiment has a certain positive effect on precipitation forecast， the skill scores of below 25 mm are improved to varying degrees in the 0~24 h forecast period， and the rainfall above 50 mm that was missed by control experiment without satellite radiance is improved by MWHS-2 data assimilation after the 6 h forecast period.The forecast results with radiance assimilation are closer to the real situation.This study is helpful to promote the operational assimilation application of satellite radiance data that is developed independently in China in regional numerical model， and then provide reference for improving prediction performance.

Abstract Objective To investigate the clinical results of transforaminal endoscopic lumbar discectomy for lumbosacral junction adolescent lumbar disc herniation with high iliac crest. Methods From February 2014 to September 2020, a retrospective analysis of 96 patients less than 21 years old with intervertebral disc herniation was carried out. We enrolled 44 patients diagnosed with lumbosacral junction disc herniation with high iliac crest who required transforaminal endoscopic lumbar discectomy. Pain in the back and the lower extremity was scored on Numeric Rating Scales (NRS) scores. Patient outcomes were graded as excellent, good, fair, and poor using modified MacNab criteria. The NRS scores before and after the operation were compared using the Wilcoxon two‐sample test. Results There were 30 male patients and 14 females. One patient underwent repeat surgery for an intervertebral disc pseudocyst. The NRS scores decreased significantly in both early and late follow‐up evaluations (p

Objective To assess the clinical efficacy of one‐stage percutaneous endoscopic lumbar discectomy (PELD) for symptomatic double‐level contiguous adolescent lumbar disc herniation (ALDH). Methods This retrospective study included 16 patients who presented with back and/or leg pain due to double‐level disc herniation underwent PELD for symptomatic lumbar disc herniation (0.27%,16/5877) from January 2014 to September 2019. After follow‐up period of 17.3 months in average, numeric rating scale (NRS) scores and modified Macnab criteria were used to assess the preoperative and postoperative clinical results. Quantitative data were expressed as mean standard deviation (SD) and the data for the variation in the NRS scores before and after the operation were compared using the Wilcoxon two‐sample test. Analyses were performed with IBM SPSS Statistics for Windows, version 19.0 (IBM, Armonk, NY, USA). Values of P

Combining theory and computation, we explore the Goos–Hänchen (GH) effect for electrons in a single-layered semiconductor microstructure (SLSM) modulated by Dresselhaus spin–orbit coupling (SOC). GH displacement depends on electron spins thanks to Dresselhaus SOC, therefore electron spins can be separated from the space domain and spin-polarized electrons in semiconductors can be realized. Both the magnitude and sign of the spin polarization ratio change with the electron energy, in-plane wave vector, strain engineering and semiconductor layer thickness. The spin polarization ratio approaches a maximum at resonance; however, no electron-spin polarization occurs in the SLSM for a zero in-plane wave vector. More importantly, the spin polarization ratio can be manipulated by strain engineering or semiconductor layer thickness, giving rise to a controllable spatial electron-spin splitter in the field of semiconductor spintronics. [ABSTRACT FROM AUTHOR]

The GJB2 gene is the most common gene responsible for hearing loss (HL) worldwide, and missense variants are the most abundant type. GJB2 pathogenic missense variants cause nonsyndromic HL (autosomal recessive and dominant) and syndromic HL combined with skin diseases. However, the mechanism by which these different missense variants cause the different phenotypes is unknown. Over 2/3 of the GJB2 missense variants have yet to be functionally studied and are currently classified as variants of uncertain significance (VUS). Based on these functionally determined missense variants, we reviewed the clinical phenotypes and investigated the molecular mechanisms that affected hemichannel and gap junction functions, including connexin biosynthesis, trafficking, oligomerization into connexons, permeability, and interactions between other coexpressed connexins. We predict that all possible GJB2 missense variants will be described in the future by deep mutational scanning technology and optimizing computational models. Therefore, the mechanisms by which different missense variants cause different phenotypes will be fully elucidated.

Titanium has excellent all-round performance, but the high cost of its production limits its widespread use. Currently, the Kroll process used to commercially produce titanium sponge is inefficient, energy-intensive, and highly polluting to the environment. Over the past few decades, many new processes have been developed to replace the Kroll process in order to reduce the cost of producing titanium and make it a common metal with as many applications as iron. These new processes can be divided into two categories: thermal reduction and electrolysis. Based on their classification, this paper reviews the current development status of various processes and analyzes the advantages and disadvantages of each process. Finally, the development direction and challenges of titanium production process are put forward.