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Abstract Thermal neutrons generated in the body during proton beam therapy (PBT) can be used to cause boron neutron capture reactions and have recently been proposed as neutron capture enhanced PBT (NCEPBT). However, the cell killing effect of NCEPBT remains underexplored. Here, we show an increase in the cell killing effect of NCEPBT. Using Monte Carlo simulations, we showed that neutrons generated by proton beam irradiation are uniformly spread on tissue culture plates. Human salivary gland tumor cell line (HSG), human osteosarcoma cell line (MG63), human tongue squamous cell carcinoma cell line (SAS), and human malignant melanoma cell line (G-361) were irradiated with X-rays, proton beams, and proton beams with 10B-enriched boronophenylalanine (boron concentration of 20 and 80 ppm). The relative biological effectiveness (RBE) values of proton beams alone, proton beams with 20 ppm boron, and proton beams with 80 ppm boron for HSG, MG63, SAS, and G-361 were 1.02, 1.07, and 1.23; 1.01, 1.08, and 1.44; 1.05, 1.09, and 1.46; and 1.04, 1.13, and 1.63, respectively. NCEPBT with high boron concentration showed high RBE and a high sensitizing effect. Our results confirm an increase in the cell killing effect of NCEPBT, should aid in its clinical use, and warrant its further investigation.

Purposes Leakage detection in underground pipelines such as prestressed concrete cylinder pipes is a crucial aspect of urban infrastructure management and maintenance. In this study, an innovative magnetic anomaly multi-feature fusion network (MMF) is designed and introduced to identify weak magnetic distribution types in underground pipelines. Methods The network leverages standard orthogonal basis functions (OBF) and minimum entropy detection (MED) features were used to comprehensively and accurately capture the complex characteristics of magnetic leakage signals. First, magnetic anomaly detection was conducted by using OBF and MED at different radial distances to acquire measured target magnetic field features. Second, an MMF was devised to integrate magnetic field features, and a multi-head attention mechanism was incorporated to capture intricate relationships and features within the sequence of magnetic fields. Finally, a multi-feature entropy weighting method was employed to allocate network weights on the basis of input feature entropy. Findings Experimental results demonstrate that the MMF network achieves a precision of 98.86% in anomaly classification, with an AUC evaluation result of 99.25%. Additionally, the model is more streamlined, exhibiting higher computational efficiency, and is capable of delivering satisfactory performance within a relatively short training period.

Abstract Background The interaction between breathing motion and scanning beams causes interplay effects in spot-scanning proton therapy for lung cancer, resulting in compromised treatment quality. This study investigated the effects and clinical robustness of two types of spot-scanning proton therapy with motion-mitigation techniques for locally advanced non-small cell lung cancer (NSCLC) using a new simulation tool (4DCT-based dose reconstruction). Methods Three-field single-field uniform dose (SFUD) and robustly optimized intensity-modulated proton therapy (IMPT) plans combined with gating and re-scanning techniques were created using a VQA treatment planning system for 15 patients with locally advanced NSCLC (70 GyRBE/35 fractions). In addition, gating windows of three or five phases around the end-of-expiration phase and two internal gross tumor volumes (iGTVs) were created, and a re-scanning number of four was used. First, the static dose (SD) was calculated using the end-of-expiration computed tomography (CT) images. The four-dimensional dynamic dose (4DDD) was then calculated using the SD plans, 4D-CT images, and the deformable image registration technique on end-of-expiration CT. The target coverage (V98%, V100%), homogeneity index (HI), and conformation number (CN) for the iGTVs and organ-at-risk (OAR) doses were calculated for the SD and 4DDD groups and statistically compared between the SD, 4DDD, SFUD, and IMPT treatment plans using paired t-test. Results In the 3- and 5-phase SFUD, statistically significant differences between the SD and 4DDD groups were observed for V100%, HI, and CN. In addition, statistically significant differences were observed for V98%, V100%, and HI in phases 3 and 5 of IMPT. The mean V98% and V100% in both 3-phase plans were within clinical limits (> 95%) when interplay effects were considered; however, V100% decreased to 89.3% and 94.0% for the 5-phase SFUD and IMPT, respectively. Regarding the significant differences in the deterioration rates of the dose volume histogram (DVH) indices, the 3-phase SFUD plans had lower V98% and CN values and higher V100% values than the IMPT plans. In the 5-phase plans, SFUD had higher deterioration rates for V100% and HI than IMPT. Conclusions Interplay effects minimally impacted target coverage and OAR doses in SFUD and robustly optimized IMPT with 3-phase gating and re-scanning for locally advanced NSCLC. However, target coverage significantly declined with an increased gating window. Robustly optimized IMPT showed superior resilience to interplay effects, ensuring better target coverage, prescription dose adherence, and homogeneity than SFUD. Trial registration: None.

Summary: Background: Dengue remains a global threat to public health, however, its disease burden among children and adolescents has always been poorly quantified. Therefore, we aimed to systematically estimate the global, regional, and national burden and temporal trends of dengue infection in children and adolescents from 1990 to 2021. Methods: Data on the number and rate of incidence and disability-adjusted life-years (DALYs) of dengue infection among children and adolescents under 20 years were obtained from the Global Burden of Disease Study (GBD) 2021. Estimated annual percentage changes (EAPCs) of the age-standardised incidence rate (ASIR) and age-standardised DALYs rate (ASDR), by age, sex, and different countries and regions, were calculated to quantify the temporal trends of dengue burden. The association between development levels (measured using the socio-demographic index [SDI]) and dengue burden was also determined. Findings: From 1990 to 2021, the global burden of dengue incidence and its associated DALYs was consistently higher in children and adolescents than in the entire population. Globally, among children and adolescents, there were 21,641,016 incident cases in 2021, an increase of 64.43% compared to 13,241,719 in 1990. The ASIR per 100,000 population increased from 587.81 in 1990 to 812.16 in 2021, with an EAPC of 1.39% (95% confidence interval [CI], 1.13%–1.65%). Besides, the number of dengue-associated DALYs among children and adolescents increased by 16.36%, from 910,458.60 in 1990 to 1,059,428.31 in 2021. The increase in DALYs was less pronounced than incidence, with the ASDR per 100,000 population increasing from 40.17 in 1990 to 41.50 in 2021, and the EAPC was only 0.67% (95% CI, 0.40%–0.95%). The incidence and DALYs burden of dengue in children and adolescents was highest in middle SDI regions, followed by low-middle SDI regions, with the lowest burden in high SDI regions. Furthermore, Tropical Latin America had an extremely high ASIR (6040.29 per 100,000 population in 2021), and Southeast Asia had an extremely high ASDR (298.20 per 100,000 population in 2021), much higher than other regions around the world. Interpretation: The global dengue burden in children and adolescents is high and has been increasing from 1990 to 2021, even though the distribution patterns vary across different countries and territories. This study first reported the global disease burden and temporal trends of children and adolescents, which has significant implications for policymakers and public health officials, as it underscores the need for age- and region-specific strategies to mitigate the growing global burden of dengue. Funding: National Natural Science Foundation of China.

Abstract Background Environmental factors greatly impact infectious disease-related mortality, yet there's a lack of comprehensive global studies on the contemporary burden and trends. This study aims to evaluate the global burden and trends of infectious disease mortality caused by air pollution, unsafe water, poor sanitation, and non-optimal temperature across Socio-Demographic Index (SDI) regions from 1990 to 2019. Methods This observational study utilized data from the Global Burden of Diseases Study to examine mortality rates from infectious diseases attributed to environmental risk factors between 1990 and 2019, including air pollution, unsafe water, sanitation, handwashing facilities (UWSH), and non-optimal temperatures. Age-standardized mortality rates (ASMRs) and estimated annual percentage change (EAPC) were utilized to present infectious disease mortality, and its trajectory influenced by environmental risk factors over the years. Nonlinear regression was conducted to explore the association between the SDI and ASMRs across regions from 1990 to 2019. Results In 2019, global infectious disease deaths linked to air pollution, UWSH, and non-optimal temperature reached a startling 2,556,992. Disease mortality varied widely across SDI regions, with the highest number of deaths due to air pollution and UWSH in Low SDI regions, and deaths from non-optimal temperature primarily in High SDI regions. Age disparities emerged, with children under five and the elderly most affected. However, an increasing mortality trend was observed among seniors (65–69, 75–79, and over 80) in High SDI regions due to enteric infections linked to UWSH. Globally, a consistent decrease in ASMR was seen from 1990 to 2019 for all diseases connected to these factors, except for respiratory infections linked to non-optimal temperature. Conclusions Our study underscores the significant impact of air pollution, UWSH, and non-optimal temperatures on global infectious disease mortality, particularly among vulnerable groups such as children and the elderly. It's important to tackle these challenges with targeted interventions aiming to enhance environmental quality, improve water and sanitation systems, and control extreme temperatures. In addition, international cooperation is essential for bridging regional disparities and driving global public health initiatives forward, thereby helping achieve Sustainable Development Goals more effectively.

Abstract This prospective cohort study aimed to identify the risk factors for post-stroke complex regional pain syndrome (CRPS) using a decision tree algorithm while comprehensively assessing upper limb and lower limb disuse and physical inactivity. Upper limb disuse (Fugl-Meyer assessment of upper extremity [FMA-UE], Action Research Arm Test, Motor Activity Log), lower limb disuse (Fugl-Meyer Assessment of lower extremity [FMA-LE]), balance performance (Berg balance scale), and physical inactivity time (International Physical Activity Questionnaire-Short Form [IPAQ-SF]) of 195 stroke patients who visited the Kishiwada Rehabilitation Hospital were assessed at admission. The incidence of post-stroke CRPS was 15.4% in all stroke patients 3 months after admission. The IPAQ, FMA-UE, and FMA-LE were extracted as risk factors for post-stroke CRPS. According to the decision tree algorithm, the incidence of post-stroke CRPS was 1.5% in patients with a short physical inactivity time (IPAQ-SF

Kenta Nakada,1,2 Kazuhiro Shimo,3 Satoshi Ohga,3 Takako Matsubara1,3 1Faculty of Rehabilitation, Kobe Gakuin University Graduate School, Kobe, Japan; 2Department of Rehabilitation, Ikeda Rehabilitation Hospital, Kurobe, Japan; 3Department of Physical Therapy, Faculty of Rehabilitation, Kobe Gakuin University, Kobe, JapanCorrespondence: Kazuhiro Shimo, Department of Physical Therapy, Faculty of Rehabilitation, Kobe Gakuin University, 518 Arise, Ikawadani-cho, Nishi-ku, Kobe, Hyogo, 651-2180, Japan, Tel/Fax +81-78-974-2461, Email shimo@reha.kobegakuin.ac.jpPurpose: This study assessed the pain associated with movement and exercise in older individuals with cognitive decline, using the Abbey Pain Scale (APS) to identify the sub-items that effectively reflect pain during such activities.Patients and Methods: A cross-sectional study was conducted in 225 older patients with musculoskeletal disorders and cognitive decline at the Ikeda Rehabilitation Hospital in Toyama, Japan. Pain during walking or transferring was assessed using the verbal rating scale (VRS) and the APS. Item response theory (IRT) was used to identify the APS sub-items that most accurately reflected the presence and degree of pain.Results: Pain associated with movement scored 1.3 ± 1.1 on the VRS and 2.5 ± 2.6 on the APS. The IRT analysis extracted “vocalization”, “facial expression”, and “change in body language” as the most reliable indicators of pain. These extracted items showed good internal consistency (Cronbach’s α = 0.72), were significantly positively related to changes in the VRS (rs = 0.370, p < 0.001), and showed significant differences between patients with and without subjective pain.Conclusion: Our study suggests that the APS sub-items “vocalization”, “facial expression”, and “change in body language” may be the most effective indicators of pain during movement and exercise in older individuals with cognitive decline. This approach may enhance the reliability of pain assessments and management during exercise therapy.Keywords: behavior observation assessments, pain assessment, pain behavior, item response theory

Vertebral artery stump syndrome (VASS) is a rare condition that can cause posterior circulation ischemic stroke due to occlusion of the ipsilateral vertebral artery (VA) orifice, resulting in blood flow stagnation and embolus formation. Although there is no established treatment for this condition, we observed 3 cases of VASS out of 326 acute ischemic stroke cases at a single institution from April 2021 to October 2022. Despite the best possible antithrombotic treatment, all 3 patients had recurrent ischemic strokes. One patient underwent drug-eluting stenting of the VA orifice to relieve occlusive flow. The other 2 patients received coil embolization, which resulted in the disappearance of their culprit collateral flow. None of the patients had recurrent ischemic strokes after endovascular intervention. Based on our observations, stenting and coil embolization are effective methods for preventing future recurrences of VASS.

Background The "Healthy China 2030" strategy has put forward higher demands for the allocation of health human resources, and more regional studies on the evaluation of the equity of health human resources have been conducted in China, but there is no overview of multiple categories of health human resources in various medical institutions from a national perspective. Objective To describe the trend and equity of 12 categories of health care institutions and 5 categories of health human resources in 31 provinces (autonomous regions and municipalities directly under the central government) nationwide from 2005-2021, so as to provide reference for the optimization of human resource allocation in various health institutions in the future. Methods National data on health human resources was collected from China Public Health Statistical Yearbook (2006-2012), China Health and Family Planning Statistical Yearbook (2013-2017) and China's Hygiene and Health Statistical Yearbook (2018-2022), demographic and economic data was collected from China Statistical Yearbook (2006-2022). The average annual growth rate and concentration index were calculated by collecting the per capita occupancy of each health human resource in medical and health institutions in each province (autonomous regions and municipalities directly under the central government) of China from 2005 to 2021, and the equity analysis was conducted based on the level of economic development. Results The total number of health personnel in China continued to rise, with an average annual growth rate of 5.58%, with faster growth in rural areas at an average annual growth rate of 10.87%; the number of health personnel in community health service centers (stations) had the fastest growth rate (average annual growth rate of 18.05%), the number of personnel in health supervision offices grew at a lower rate (average annual growth rate of 0.18%), and the number of personnel in disease prevention and control centers showed a decreasing trend (average annual growth rate of -0.39%). Except for community health service centers (stations), the concentration index of the total number of health personnel in all types of medical institutions was

Background: There is only limited research on the coronal cementum of a tooth, and the mechanisms of its forming process are not well-defined. This report presents a coronal cementum on the occlusal surfaces of enamel in an impacted wisdom tooth in a human, which is not nearly the cervical portion. Materials and Methods: The tooth (Tooth #1) was derived from a 46-year-old female. Histological analysis, including hematoxylin and eosin (HE) and toluidine blue (TB) staining, and Scanning Electron Microscopy and Energy Dispersive X-ray Spectrometer (SEM-EDS) analysis of the extracted tooth were conducted. Radiographic examination showed that Tooth #1 was horizontally impacted in the maxilla and had the apex of a single root placed between the buccal and palatal roots of Tooth #2. Results: Coronal cementum was distributed widely on the enamel, and reduced enamel epithelium was also found with enamel matrix proteins histologically. The formation of acellular cementum was observed to be more predominant than that of the cellular cementum in Tooth #1. SEM showed that the occlusal cementum connected directly with enamel. Calcium mapping revealed an almost similar occlusal cementum and enamel. In addition, the spectrum of elements in coronal cementum resembled the primary cementum according to SEM-EDS. Discussion: Thus, coronal cementogenesis in impacted human teeth might be related to the existence of reduced enamel epithelium.

Full-length anchorage rockbolts are widely used in roadway reinforcement and rock controlling in underground mining. This article proposes using an elastic–debonding (ED) model to analyse the axial performance of rockbolts. The advantage of this ED model was that the full force–deformation curve of rockbolts comprised only three phases, which was relatively simpler to calculate. Its effectiveness was compared with experiment tests. Based on the ED model, a series of parameter studies was conducted. Results showed that for cross-section area of rock, there was a critical range. Once the cross-section area of rock was beyond that critical range, external rock had a mild impact on the axial performance of rockbolts. Rockbolt diameter significantly affected the axial performance of rockbolts. When rock diameter increased, the peak force of rockbolts increased linearly, while deformation at the peak force decreased non-linearly. The corresponding calculation equation between the peak force, deformation at the peak force, and rockbolt diameter was obtained. Borehole diameter had a mild impact on the axial performance of rockbolts. Increasing rockbolt length benefits improving the peak force of rockbolts. Rockbolt modulus of elasticity had a more apparent impact on the deformation at peak force. Mechanical properties of the bolt/grout (b/g) face affected the axial performance of rockbolts. Increasing the b/g face strength improved the peak force of rockbolts. Slippage at the ultimate load had a more apparent impact on the turning point between the elastic phase and the elastic–softening phase.

Background: Recent studies have shown that receptor status of breast cancer change between primary tumor and recurrence, which may influence treatment strategy and prognosis, but there are few reports on receptor discordance between primary tumors and local recurrence (LR) after nipple-sparing mastectomy (NSM). Patients and methods: We collected 74 patients who had LR after NSM for newly diagnosed stages 0 to 3 breast cancer between 2008 and 2016 at 14 institutions. We classified into 4 subtypes based on hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2). We evaluated clinicopathological factors that correlate with receptor discordance and assessed the impact of receptor discordance on survival. Results: Discordance rates in estrogen receptor (ER), progesterone receptor (PgR) and HER2 were 9.5, 10.8 and 5.4 %, respectively. The most common change was from HR-/HER2+ to HR+/HER2+, and this pattern of receptor change occurred only in patients with nipple–areolar recurrence. Non-invasive tumors in LR, nipple–areolar recurrence (NAR), HR-/HER2+ primary tumor subtype, and the presence of chemotherapy for primary tumors were significantly associated with receptor discordance. With a median follow-up of 44.5 months (4–153 months), patients in the receptor-discordant group had no disease-free survival (DFS) event after LR resection (5-year DFS; 100 % in the receptor-discordant group vs 85.1 % in the receptor-concordant group; p = 0.2). Conclusion: Our study demonstrates that the presence of chemotherapy for primary tumors, nipple-areolar recurrence, and its related factors (non-invasive tumor in LR, HR-/HER2+ primary tumor subtype) were associated with receptor discordance. However, further studies with longer follow-up periods and larger sample sizes are needed.

The optimal time to ambulation remains unclear for intensive care unit (ICU) patients following abdominal surgery. While previous studies have explored various mobilization techniques, a direct comparison between ambulation and other early mobilization methods is lacking. Additionally, the impact of time to ambulation on complications and disuse syndrome prevention requires further investigation. This study aimed to identify the optimal time to ambulation for ICU patients after abdominal surgery and considered its potential influence on complications and disuse syndrome. We examined the relationship between time to ambulation and hospital length of stay (LOS). Patients were categorized into the nondelayed (discharge within the protocol time) and delayed (discharge later than expected) groups. Data regarding preoperative functioning, postoperative complications, and time to discharge were retrospectively collected and analyzed. Of the 274 postsurgical patients managed in the ICU at our hospital between 2018 and 2020, 188 were included. Time to ambulation was a significant prognostic factor for both groups, even after adjusting for operative time and complications. The area under the curve was 0.72, and the cutoff value for time to ambulation was 22 h (sensitivity, 68%; specificity, 77%). A correlation between time to ambulation and complications was observed, with both impacting the hospital LOS (model 1: p < 0.01, r = 0.22; model 2: p < 0.01, r = 0.29). Specific cutoff values for time to ambulation will contribute to better surgical protocols.

Staphylococcus aureus biofilm is a common bio-contaminant source that leads to food cross-contamination and foodborne disease outbreaks. Hence, there is a need for searching novel antibiofilm agents with potential anti-virulence properties to control S. aureus contamination and infections in food systems. In this study, the antibiofilm effects of lactobionic acid (LBA) against S. aureus and its influence on virulence were explored. The minimum inhibition concentration of LBA on S. aureus was 8 mg/mL. Viable count and crystal violet assays revealed that LBA inhibited and inactivated S. aureus biofilms. Microscopic observations further confirmed the antibiofilm activity of LBA on S. aureus that disrupted the biofilm architecture and inactivated the viable cells in biofilms. Moreover, LBA decreased the release of extracellular DNA (eDNA) and extracellular polysaccharide (EPS) in S. aureus biofilms. LBA suppressed biofilm formation by intervening metabolic activity and reduced virulence secretion by repressing the hemolytic activity of S. aureus. Furthermore, LBA altered the expressions of biofilm- and virulence-related genes in S. aureus, further confirming that LBA suppressed biofilm formation and reduced the virulence secretion of S. aureus. The results suggest that LBA might be useful in preventing and controlling biofilm formation and the virulence of S. aureus to ensure food safety.

Abstract Polymer dielectrics with excellent thermal resistance and superior energy storage behaviour are extensively demanded with the increasing development of film capacitors applied in hostile environments. In this study, novel diamine with sulfonyl‐containing side chain was designed and synthesised. The corresponding polyimide (PI) dielectrics derived from the sulfonyl‐containing diamine were prepared, so were the polyimides possessing the same backbone but without side chains. Consequently, superior thermal resistance of glass transition temperature ranged from 162–208°C was obtained. Moreover, the polyimides presented permittivity of 3.34–5.89 at 1 kHz, Weibull breakdown strength of 377–538 MV/m and discharged energy density of 3.82–5.85 J/cm3. In particular, sulfonyl‐containing polyimide of SPI‐2 with flexible backbone and sulfonyl side chain indicates the highest discharged energy density and charge‐discharge efficiency simultaneously. The introduction of the strong polar sulfonyl group in the side chain enhances dielectric and energy storage properties effectively. In addition, it is found that the dipolar moment density (μ/Vvdw) calculated from molecular simulation is closely correlated to permittivity measured from experiments. The combined method of molecular simulation and experiments would offer an effective approach to assist in molecular design of high‐performance polymer dielectrics.

Abstract. Introduction:. Movement-evoked pain (MEP) is the primary symptom in patients with knee osteoarthritis (KOA). Objectives:. This study aimed to investigate the contribution of joint structural changes and pain sensitization to the mechanisms of MEP in patients with KOA. Methods:. A total of 86 patients were assessed for demographic characteristics, osteoarthritis severity, Whole-Organ Magnetic Resonance Imaging Score–Hoffa synovitis and bone marrow lesions, pressure pain threshold and temporal summation of pain at the knee and forearm, Central Sensitization Inventory-9, and MEP. In measure of MEP, knee pain was scored using a numerical rating scale (NRS, 0–10) before and every minute during a 6-minute walking test (6MWT), and the MEP index was defined as the change in NRS pain score from baseline to the sixth minute of walking. Result:. On average, pain during 6MWT increased by 1.4 ± 1.5 points on the NRS relative to baseline, with 30.2% of patients showing an increase of 2 points or more. The hierarchical linear regression analysis revealed that Hoffa synovitis, pressure pain threshold at the forearm, and temporal summation of pain at the knee were associated with the MEP index. Conclusion:. The findings of this study suggest that both synovitis and neural mechanisms, such as pain sensitization, play a role in the development of MEP in KOA.

BackgroundNon-motor symptoms (NMS) are important factors when selecting treatments for patients with advanced Parkinson's disease (PD). We sought to elucidate the prescribing practices for advanced PD patients with NMS in Japanese clinical practice.MethodsWe examined the prescription rates and doses of anti-PD drugs, and the use of non-steroidal anti-inflammatory drugs (NSAIDs) in post hoc analyses of a 52-week observational study of 996 PD patients with wearing-off on levodopa-containing therapy and ≥1 NMS.ResultsDopamine agonists were the most frequently prescribed drugs combined with levodopa-containing drugs, followed by entacapone, zonisamide, istradefylline, selegiline, and amantadine. The daily dose of levodopa-containing drugs, rotigotine, entacapone, istradefylline, and droxidopa, and the levodopa-equivalent dose increased during the observation period. In a subgroup analysis of patients stratified by NMS status (improved/unchanged/deteriorated), the deteriorated group had higher prescription rates of entacapone and istradefylline, whereas the improved group had higher prescription rates of NSAIDs and zonisamide at Week 52. Prescriptions varied by geographical region for anti-PD drugs and by NMS status for NSAIDs.ConclusionsThere were significant changes in the prescriptions and dosing of selected anti-PD drugs, especially newer drugs. Anti-PD drug and NSAID prescriptions also varied by changes in NMS status and geographic region.

Pre-messenger RNA (pre-mRNA) splicing modulation is an attractive approach for investigating the mechanisms of genetic disorders caused by mis-splicing. Previous reports have indicated that a modified U7 small nuclear RNA (U7 snRNA) is a prospective tool for modulating splicing both in vitro and in vivo. To date, very few studies have investigated the role of antisense sequence length in modified U7 snRNA. In this study, we designed a series of antisense sequences with various lengths and evaluated their efficiency in inducing splicing modulation. To express modified U7 snRNAs, we constructed a series of plasmid DNA sequences which codes cytomegalovirus (CMV) enhancer, human U1 promoter, and modified mouse U7 snRNAs with antisense sequences of different lengths. We evaluated in vitro splicing modulation efficiency using a luciferase reporter system for simple and precise evaluation as well as reverse transcription-polymerase chain reaction to monitor splicing patterns. Our in vitro assay findings suggest that antisense sequences of modified mouse U7 snRNAs have an optimal length for efficient splicing modulation, which depends on the target exon. In addition, antisense sequences that were either too long or too short decreased splicing modulation efficiency. To confirm reproducibility, we performed an in vitro assay using two target genes, mouse Fas and mouse Dmd. Together, our data suggests that the antisense sequence length should be optimized for modified mouse U7 snRNAs to induce efficient splicing modulation.

[This corrects the article DOI: 10.1371/journal.pone.0071093.].

ObjectiveTo evaluate whether orthostatic hypotension (OH) or supine hypertension (SH) is associated with brain atrophy and white matter hyperintensities (WMH), we analyzed clinical and radiologic data from a large multicenter consortium of patients with Parkinson disease (PD) and dementia with Lewy bodies (DLB).MethodsSupine and orthostatic blood pressure (BP) and structural MRI data were extracted from patients with PD and DLB evaluated at 8 tertiary-referral centers in the United States, Canada, Italy, and Japan. OH was defined as a systolic/diastolic BP fall ≥20/10 mm Hg within 3 minutes of standing from the supine position (severe ≥30/15 mm Hg) and SH as a BP ≥140/90 mm Hg with normal sitting BP. Diagnosis-, age-, sex-, and disease duration-adjusted differences in global and regional cerebral atrophy and WMH were appraised with validated semiquantitative rating scales.ResultsA total of 384 patients (310 with PD, 74 with DLB) met eligibility criteria, of whom 44.3% (n = 170) had OH, including 24.7% (n = 42) with severe OH and 41.7% (n = 71) with SH. OH was associated with global brain atrophy (p = 0.004) and regional atrophy involving the anterior-temporal (p = 0.001) and mediotemporal (p = 0.001) regions, greater in severe vs nonsevere OH (p = 0.001). The WMH burden was similar in those with and without OH (p = 0.49). SH was not associated with brain atrophy (p = 0.59) or WMH (p = 0.72).ConclusionsOH, but not SH, was associated with cerebral atrophy in Lewy body disorders, with prominent temporal region involvement. Neither OH nor SH was associated with WMH.