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While it is widely thought that de novo mutations (DNMs) occur randomly, we previously showed that some DNMs are enriched because they are positively selected in the testes of aging men. These "selfish" mutations cause disorders with a shared presentation of features, including exclusive paternal origin, significant increase of the father's age, and high apparent germline mutation rate. To date, all known selfish mutations cluster within the components of the RTK-RAS-MAPK signaling pathway, a critical modulator of testicular homeostasis. Here, we demonstrate the selfish nature of the SMAD4 DNMs causing Myhre syndrome (MYHRS). By analyzing 16 informative trios, we show that MYHRS-causing DNMs originated on the paternally derived allele in all cases. We document a statistically significant epidemiological paternal age effect of 6.3 years excess for fathers of MYHRS probands. We developed an ultra-sensitive assay to quantify spontaneous MYHRS-causing SMAD4 variants in sperm and show that pathogenic variants at codon 500 are found at elevated level in sperm of most men and exhibit a strong positive correlation with donor's age, indicative of a high apparent germline mutation rate. Finally, we performed in vitro assays to validate the peculiar functional behavior of the clonally selected DNMs and explored the basis of the pathophysiology of the different SMAD4 sperm-enriched variants. Taken together, these data provide compelling evidence that SMAD4, a gene operating outside the canonical RAS-MAPK signaling pathway, is associated with selfish spermatogonial selection and raises the possibility that other genes/pathways are under positive selection in the aging human testis.
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As the plasma beta (ß) increases in high-performance tokamaks, electromagnetic turbulence becomes more significant, potentially constraining their operational range. To investigate this turbulence, a cross-polarization scattering (CPS) diagnostic system is being developed on the HL-3 tokamak for simultaneous measurements of density and magnetic fluctuations. In this work, a quasi-optical system has been designed and analyzed for the Q-band CPS diagnostic. The system includes a lens group for beam waist size optimization, a rotatable wire-grid polarizer for polarization adjustment, and a reflector group for measurement range regulation and system response enhancement. Laboratory tests demonstrated a beam radius of order 4 cm at the target measurement location (near the plasma pedestal), cross-polarization isolation exceeding 30 dB, and poloidal and toroidal angle adjustment ranges of ±40° and ±15°, respectively. These results verify the system's feasibility through laboratory evaluations. The quasi-optical system has been installed on the HL-3 tokamak during the 2023 experimental campaign to support the development of CPS diagnostics.
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Plasma Position Reflectometry (PPR) is planned to provide plasma position and shape information for plasma operation in future fusion reactors. Its primary function is to calibrate the drift of the magnetic signals due to the integral nature of magnetic measurement. Here, we attempt to measure plasma position using ordinary mode (O-mode) and extraordinary mode (X-mode) reflectometry systems on two tokamaks. A new physical model based on the phase shift is proposed to deduce the relative movement of the cut-off layer without density inversion. We demonstrate the plasma position measurements by absolute measurement from density profile inversion and relative measurement from phase shift. The combination of X-mode and O-mode reflectometers can minimize the limitations of single polarization reflectometry and further increase the accuracy of plasma position measurement. These results could provide an important technical basis for the further development of a real-time control system based on PPR.
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A 105 GHz collective Thomson scattering (CTS) diagnostic has been successfully developed for fast-ion measurements on the HL-2A tokamak, and it has been deployed during an experimental campaign. Enhanced signals exhibiting synchronous modulation characteristics have been observed across all CTS channels upon the launch of a modulated probe wave. Results show that the intensity of the CTS signal increases with Neutral Beam Injection (NBI) power and is proportional to neutron count, indicating that the scattering signal contains a contribution from fast ions. Compared with the signal without NBI, the enhanced scattering spectrum due to NBI is slightly wider than the predicted fast ion range. Such broadening might be attributed to the heating effects of the gyrotron.
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Objective: To investigate the efficacy and safety of transbronchial cryobiopsy (TBCB) after lung transplantation. Methods: The clinical characteristics, TBCB procedure, diagnosis and treatment, and outcomes of lung transplant recipients of 6 patients (all male, aged 33-67 years) with TBCB in China-Japan Friendship Hospital from May to November 2021 were retrospectively analyzed. Results: Among the 6 patients diagnosed by TBCB, there were 2 cases of organizing pneumonia, 1 acute cellular rejection, 1 antibody-mediated rejection, and 1 bronchiolitis obliterans, and 1 diffuse alveolar damage. After the clinical diagnosis was confirmed, the condition improved after adjustment of the treatments followed. There were no serious complications related to the TBCB procedure. Conclusion: TBCB is valuable and relatively safe in the diagnosis of complications after lung transplantation, but the indications need to be strictly controlled.
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Enfermedades Pulmonares Intersticiales , Trasplante de Pulmón , Humanos , Masculino , Biopsia/métodos , Broncoscopía/efectos adversos , Broncoscopía/métodos , Pulmón/patología , Enfermedades Pulmonares Intersticiales/etiología , Enfermedades Pulmonares Intersticiales/complicaciones , Trasplante de Pulmón/efectos adversos , Complicaciones Posoperatorias/diagnóstico , Estudios Retrospectivos , Adulto , Persona de Mediana Edad , AncianoAsunto(s)
COVID-19 , Compuestos Orgánicos Volátiles , Humanos , COVID-19/diagnóstico , Sistema Respiratorio , Tamizaje Masivo , EspiraciónRESUMEN
A synthetic electron cyclotron emission (ECE) diagnostic is used to interpret ECE signals from preset plasma equilibrium profiles, including magnetic field, electron density, and electron temperature. According to the simulation results, the electron temperature (Te) profile covering the harmonic overlap region can be obtained by receiving ECE signals at the high field side (HFS) of the HL-2M plasma. The third harmonic ECE at the low field side (LFS) cannot pass through the second harmonic resonance layer at the HFS unless the optical thickness (τ) of the second harmonic becomes gray (τ ≤ 2). In addition, the impact of the relativistic frequency down-shift has been evaluated and corrected. The measurable range of the HFS ECE has been calculated by scanning different parameters (electron density, temperature, and magnetic field). Higher plasma parameters allow a wider radial range of electron temperature measurements. The minimum inner measurable position can reach R = 120 cm (r/a = -0.89) when the product of core temperature (Te0) and density (ne0) is greater than 35 × 1019 keV m-3, which is extended by more than 30 cm inward compared with that of the LFS measurement. The HFS ECE will greatly improve the diagnostic ability of ECE systems on the HL-2M tokamak.
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OBJECTIVE: Clubfoot is a growing public health concern in Bangladesh, with the incidence of approximately 0.64 to 6.8 in every 1000 live births. For over a decade, Ponseti method has been considered a gold standard for treating the clubfoot. Despite few studies have been estimating the number of casts required to correct the clubfoot deformities by Ponseti method, the subject of interest has always remained. Therefore, this current study aimed to investigate the significant predictive factors for the number of casts required to correct congenital clubfoot. PATIENTS AND METHODS: In this retrospective cohort study, we used Bayesian Poisson Regression Model to investigate the influencing factors that could predict how many casts are needed to correct the clubfoot. We included 69 patients with 99 affected feet, who completed their corrective phase of treatment in the Ponseti method. For this cohort study, we integrated only pre-tenotomy casting data with no age restrictions. We used Bayesian Poisson regression analysis technique to estimate the predictive factors. RESULTS: In Bayesian Poisson model, age was the most influencing predictive factor (24.3%) for increasing the number of castings to correct the clubfoot deformity. The clubfoot offspring of the ≤1-year-old was positive, and the incidence rate increased significantly with the casting number. The number of Ponseti casts in male clubfoot children was 28% higher than in female, and this was marginally statistically significant. There was no marked change estimated in the pattern of clubfoot, foot involvement and Pirani score of the severity. CONCLUSIONS: We concluded that the age factor may influence the number of casts required for the correction of clubfoot and specifically ≤ 1-year-old children are highly impacted. Treating clubfoot at an early age is suggested in this study to increase the success of clubfoot treatment and decrease the risk of relapse.
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Pie Equinovaro , Teorema de Bayes , Moldes Quirúrgicos , Niño , Pie Equinovaro/terapia , Estudios de Cohortes , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
A solid state terahertz interferometer has been developed on the recent commissioned HL-2M tokamak. It can work in a wide frequency region of 220-325 GHz, and the terahertz wave is generated from a low frequency phase locked voltage controlled oscillator with the frequency multiplying technique. A phase processor based on field programmable gate array (FPGA) technology is designed for the heterodyne interferometer, and it contributes to real-time display of electron density. To extract phase information, a novel numerical algorithm related to fast Fourier transform is written on the FPGA chip and enables one to obtain phase shift without being affected by amplitude variation induced by plasma absorption or frequency modulation from the outer electromagnetic environment. The interferometer achieves minimum measurable electron density in the order of 1016 m-3. With the plasma diagnosis, electron density and low frequency tearing mode have been measured during the first experimental campaign.
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Remote control of the diagnostic systems is the basic requirement for the high performance plasma operation in a fusion device. This work presents the development of the remote control system for the multichannel Doppler backward scattering (DBS) reflectometers. It includes a remote controlled quasi-optical system and a remote intermediate frequency (IF) amplifier gain control system. The quasi-optical system contains a rotational polarizer, its polarization angle is tunable through a remote controlled motor, and it could combine the microwave beams with a wide frequency range into one focused beam. The remote IF gain control system utilizes the digital microcontroller (MCU) technique to regulate the signal amplitude for each signal channel. The gain parameters of amplifiers are adjustable, and the feedback of working status in the IF system will be sent to MCU in real time for safe operation. The gain parameters could be controlled either by the Ethernet remote way or directly through the local control interface on the system. Preliminary experimental results show the effectiveness of the remote controlled multichannel DBS system.
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OBJECTIVE: COVID-19 has become a global public health emergency affecting 223 countries and territories, and it drastically changed the life of public and health care delivery systems. Although many guidelines have been proposed to avoid infection from COVID-19 and to promote the use of telerehabilitation, there is still no clear answer for the current scenario and strategies of therapists' practice during the COVID-19 pandemic lockdown. This study aimed to explore the impact of COVID-19 lockdown on Occupational Therapists' (OTs) practice, the use of telerehabilitation strategies by OTs, and their employment and mental health. Also, this study aimed to explore the OTs perspective on the role of telerehabilitation during this pandemic lockdown. MATERIALS AND METHODS: Online cross-sectional survey was conducted between April 2020 and May 2020. RESULTS: 114 OTs completed the survey. The results of this study showed that 52.8% of therapists had stress and anxiety due to COVID-19 lockdown. We found that 60.7% of OTs (n=65) used telerehabilitation, versus 36.1% (n=39) before the lockdown. Telerehabilitation approaches were mostly implemented during this lockdown for children with autistic problems (66.6%), stroke (12.9%), cerebral palsy (6.4%), learning disabilities (9.6%), Parkinson's diseases (1.6%), and other medical conditions (2.8%). 10% of therapists reported that they lost their job, and 76% reported that this lockdown affected their income negatively. Overall, 87.8% of therapists reported that mobile technology was very useful to overcome the stress due to COVID-19 related lockdown, social isolation, and social distancing. CONCLUSIONS: The COVID-19 pandemic lockdown experiences made us rethink the current approach of therapy services into alternative method (mixed mode) delivery of occupational therapy practice, which is including the combined method of video-based (telerehabilitation) consultation and face to face intervention.
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COVID-19/epidemiología , Terapia Ocupacional/tendencias , Aceptación de la Atención de Salud , Cuarentena/tendencias , Telerrehabilitación/tendencias , Adulto , Anciano , COVID-19/prevención & control , Control de Enfermedades Transmisibles/métodos , Control de Enfermedades Transmisibles/tendencias , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia Ocupacional/métodos , Pandemias , Cuarentena/métodos , Telerrehabilitación/métodos , Adulto JovenRESUMEN
OBJECTIVE: To explore possible mechanism of ERBB2 gene expression silencing mediating mitogen-activated protein kinase 1/mitogen-activated protein kinase 3 (MAPK1/MAPK3) signaling pathway on proliferation, migration, and invasion of ovarian cancer cells. PATIENTS AND METHODS: A total of 240 cancer specimens were collected in patients with epithelial ovarian cancer intraoperatively in our hospital from January 2015 to January 2018. Expressions of ERBB2, MAPK1, and MAPK3 in tissues were detected by immunohistochemistry. Following the culture of ovarian cancer cell lines, target cell line with high expression of ERBB2 was screened by qRT-PCR. Cell grouping was performed with four groups after transfection, including Blank group, negative control (NC) group, ERBB2 shRNA group, and ERBB2 overexpression group (shorted as ERBB2 group). The expression levels of ERBB2, MAPK1, MAPK3, vascular endothelial growth factor (VEGF), metalloproteases-2 (MMP-2), and tissue inhibitor of metalloproteases-2 (TIMP-2) were detected by qRT-PCR in different transfection groups, followed by the detection of protein expressions with Western blot. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to test the proliferation activity of each group after transfection, while transwell assay and scratch test explored cell invasion and migration in each group, respectively. RESULTS: Immunohistochemistry showed that the positive rates of ERBB2, MAPK1, and MAPK3 in ovarian cancer tissues were significantly increased than those in adjacent normal epithelial tissues. In the cell experiment, ERBB2 gene was highly expressed in SKOV3 ovarian cancer cell line. There was no significant difference in each index between Blank group and NC group (p > 0.05). Compared with Blank group and NC group, the expression levels of ERBB2, MAPK1, MAPK3, VEGF, and MMP-2 in ERBB2 shRNA group decreased significantly, TIMP-2 increased markedly, and proliferation, invasion, and migration abilities of cells decreased markedly after transfection, showing statistically significant differences (All p < 0.05). By contrast, the expression levels of ERBB2, MAPK1, MAPK3, VEGF, and MMP-2 increased remarkably in ERBB2 group, while TIMP-2 decreased significantly, and cell proliferation, invasion, and migration ability increased evidently after transfection, with statistically significant differences (All p < 0.05). CONCLUSIONS: Silencing ERBB2 gene expression may inhibit the activation of MAPK1/MAPK3 signaling pathway and thus suppress the proliferation, invasion, and migration of ovarian cancer cells. Overexpression of ERBB2 gene can reverse those trends, which in turn support the role of ERBB2 gene expression silencing in molecular targeted therapy of ovarian cancer.
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Movimiento Celular , Silenciador del Gen , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Receptor ErbB-2/genética , Transducción de Señal , Células Cultivadas , Femenino , Humanos , Proteína Quinasa 1 Activada por Mitógenos/genética , Proteína Quinasa 3 Activada por Mitógenos/genética , Invasividad Neoplásica , Receptor ErbB-2/metabolismo , Transducción de Señal/genéticaRESUMEN
Identity development within the interprofessional field is an emerging area of research. This scoping review aims to establish how professional and interprofessional identities are defined, conceptualized, theorized and measured within the interprofessional literature. Six databases were systematically searched for papers focusing on professional and/or interprofessional identities in interprofessional healthcare and education using a scoping review methodology. A total of 84 papers were included. Most papers discussed professional identity only; the minority discussed both identities. There were three key findings. First, no universal definition of interprofessional identity exists. Second, there is no shared understanding of interprofessional identity and its relationship with professional identity. Third, poor alignment between definitions, conceptualizations, theories and measures of interprofessional identity exists. The absence of a psychometrically robust instrument that specifically measures interprofessional identity and the short-term focus of current interprofessional identity research further limits understanding. Research that critically examines professional and interprofessional identity development should be underpinned by clear definitions, concepts, theories and measures of both identities. High-quality research will allow greater understanding of interprofessional identity development and its impact on interprofessional practice.
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The global number of people over the age of 60 years is expected to increase from 970 million to 2.1 billion in 2050 and 3.1 billion in 2100. About 80% of the aging population will be in the developing countries. Aging population may suffer from various physical, cognitive, and social problems, due to aging process such as impairment of physical related functions (decreased mobility and walking speed, falls, frailty, decreased walking speed, difficulties in basic, and instrumental activities of daily living), cognitive related functions (memory-related issues), sensory functions (hearing loss, cataracts and refractive errors, presbyopia, decreased vestibular function), behavioural and psychological disorders, social isolation issues, and poor quality of life. Over the period of the last few decades, emerging technologies such as internet of things (IoT), artificial intelligence (AI), sensors, cloud computing, wireless communication technologies, and assistive robotics have given the vision to develop various ambient or active assisted living (AAL) approaches for supporting an elderly people to live safely and independently in their living environment and participate in their daily and community activities, as well as supporting them to maintain their physical, mental health, and quality of their life. The aim of this paper is to review the use of Ambient or Active Assisted Living for older adults with physical, cognitive impairments, and their social participation.
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Actividades Cotidianas , Inteligencia Ambiental , Disfunción Cognitiva/rehabilitación , Fragilidad/rehabilitación , Dispositivos de Autoayuda , Anciano , Anciano de 80 o más Años , Envejecimiento/fisiología , Envejecimiento/psicología , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/psicología , Anciano Frágil/psicología , Fragilidad/fisiopatología , Fragilidad/psicología , Humanos , Vida Independiente/psicología , Esperanza de Vida/tendencias , Salud Mental , Aptitud Física/fisiología , Aptitud Física/psicología , Calidad de VidaRESUMEN
Nearly all adults harbor acute myeloid leukemia (AML)-related clonal hematopoietic mutations at a variant allele fraction (VAF) of ≥0.0001, yet relatively few develop hematologic malignancies. We conducted a nested analysis in the Nurses' Health Study and Health Professionals Follow-Up Study blood subcohorts, with up to 22 years of follow up to investigate associations of clonal mutations of ≥0.0001 allele frequency with future risk of AML. We identified 35 cases with AML that had pre-diagnosis peripheral blood samples and matched two controls without history of cancer per case by sex, age, and ethnicity. We conducted blinded error-corrected sequencing on all study samples and assessed variant-associated risk using conditional logistic regression. We detected AML-associated mutations in 97% of all participants (598 mutations, 5.8/person). Individuals with mutations ≥0.01 variant allele fraction had a significantly increased AML risk (OR 5.4, 95%CI: 1.8-16.6), as did individuals with higher-frequency clones and those with DNMT3A R882H/C mutations. The risk of lower-frequency clones was less clear. In the 11 case-control sets with samples banked ten years apart, clonal mutations rarely expanded over time. Our findings are consistent with published evidence that detection of clonal mutations ≥0.01 VAF identifies individuals at increased risk for AML. Further study of larger populations, mutations co-occurring within the same pre-leukemic clone and other risk factors (lifestyle, epigenetics, etc.), are still needed to fully elucidate the risk conferred by low-frequency clonal hematopoiesis in asymptomatic adults.
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Biomarcadores de Tumor/genética , Evolución Clonal , Células Clonales/patología , Hematopoyesis , Leucemia Mieloide Aguda/patología , Mutación , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Frecuencia de los Genes , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Leucemia Mieloide Aguda/etiología , Masculino , Persona de Mediana Edad , Pronóstico , Factores de RiesgoRESUMEN
INTRODUCTION: Adolescent idiopathic scoliosis (AIS) is a common musculoskeletal disorder with strong evidence for a genetic contribution. CNVs play an important role in congenital scoliosis, but their role in idiopathic scoliosis has been largely unexplored. METHODS: Exome sequence data from 1197 AIS cases and 1664 in-house controls was analysed using coverage data to identify rare CNVs. CNV calls were filtered to include only highly confident CNVs with >10 average reads per region and mean log-ratio of coverage consistent with single-copy duplication or deletion. The frequency of 55 common recurrent CNVs was determined and correlated with clinical characteristics. RESULTS: Distal chromosome 16p11.2 microduplications containing the gene SH2B1 were found in 0.7% of AIS cases (8/1197). We replicated this finding in two additional AIS cohorts (8/1097 and 2/433), resulting in 0.7% (18/2727) of all AIS cases harbouring a chromosome 16p11.2 microduplication, compared with 0.06% of local controls (1/1664) and 0.04% of published controls (8/19584) (p=2.28×10-11, OR=16.15). Furthermore, examination of electronic health records of 92 455 patients from the Geisinger health system showed scoliosis in 30% (20/66) patients with chromosome 16p11.2 microduplications containing SH2B1 compared with 7.6% (10/132) of controls (p=5.6×10-4, OR=3.9). CONCLUSIONS: Recurrent distal chromosome 16p11.2 duplications explain nearly 1% of AIS. Distal chromosome 16p11.2 duplications may contribute to scoliosis pathogenesis by directly impairing growth or by altering expression of nearby genes, such as TBX6. Individuals with distal chromosome 16p11.2 microduplications should be screened for scoliosis to facilitate early treatment.
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Proteínas Adaptadoras Transductoras de Señales/genética , Duplicación Cromosómica , Cromosomas Humanos Par 16 , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Escoliosis/diagnóstico , Escoliosis/genética , Estudios de Casos y Controles , Mapeo Cromosómico , Biología Computacional/métodos , Variaciones en el Número de Copia de ADN , Femenino , Estudios de Asociación Genética/métodos , Heterocigoto , Humanos , Masculino , Fenotipo , Escoliosis/epidemiología , Eliminación de Secuencia , Secuenciación del ExomaRESUMEN
Disruptions have the potential to cause severe damage to large tokamaks like ITER. The mitigation of disruption damage is one of the essential issues for the tokamak. Massive gas injection (MGI) is a technique in which large amounts of a noble gas are injected into the plasma in order to safely radiate the plasma energy evenly over the entire plasma-facing wall. However, the radiated energy during the disruption triggered by massive gas injection is found to be toroidally asymmetric. In order to investigate the spatial and temporal structures of the radiation asymmetry, the radiated power diagnostics for the J-TEXT tokamak have been upgraded. The multi-channel arrays of absolute extreme ultraviolet photodiodes have been upgraded at four different toroidal positions to investigate the radiation asymmetries during massive gas injection. It is found that the toroidal asymmetry is associated with plasma properties and MGI induced MHD activities.
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Fast electron bremsstrahlung (FEB) emission during Ohmic discharge experiments on the Joint Texas Experimental Tokamak (J-TEXT) has been measured by a recently developed vertical multi-channel FEB diagnostic based on CdZnTe detectors. There are 5 sight lines to observe the vertical emission of fast electrons at the high-field side with a spatial resolution of 5 cm. The FEB emission in the energy range of 30-300 keV can be measured. The generation of fast electrons accelerated by loop voltage has been confirmed during the early phase of discharge by analyzing the signals of FEB emission. The runaway electron beam instabilities have been observed with the FEB diagnostic on J-TEXT.
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Disruptions have the possibility of causing severe wall damage to large tokamaks like ITER. The mitigation of disruption damage is essential to the safe operation of a large-scale tokamak. The shattered pellet injection (SPI) technique, which is regarded as the primary injection method for ITER, presents several advantages relative to massive gas injection, including more rapid particle delivery, higher total particle assimilation, and more centrally peaked particle deposition. A dedicated argon SPI system that focuses on disruption mitigation and runaway current dissipation has been designed for the Joint Texas Experimental Tokamak (J-TEXT). A refrigerator is used to form a single argon pellet at around 64 K. The pellet will be shaped with a 5 mm diameter and a 1.5-10 mm length. Helium gas at room temperature will be used as a propellant gas for pellet acceleration. The pellet can be injected with a speed of 150-300 m/s. The time interval between injection cycles is about 8 min. The pellet will be shattered at the edge of the plasma and then injected into the core of plasma. The first experiments of SPI fast shutdown and runaway current dissipation have been performed.