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TAR DNA-binding protein 43 (TDP-43) is a highly conserved nuclear RNA/DNA-binding protein involved in the regulation of RNA processing. The accumulation of TDP-43 aggregates in the central nervous system is a common feature of many neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer’s disease (AD), and limbic predominant age-related TDP-43 encephalopathy (LATE). Accumulating evidence suggests that prion-like spreading of aberrant protein aggregates composed of tau, amyloid-β, and α-synuclein is involved in the progression of neurodegenerative diseases such as AD and PD. Similar to those of prion-like proteins, pathological aggregates of TDP-43 can be transferred from cell-to-cell in a seed-dependent and self-templating manner. Here, we review clinical and experimental studies supporting the prion-like spreading of misfolded TDP-43 and discuss the molecular mechanisms underlying the propagation of these pathological aggregated proteins. The idea that misfolded TDP-43 spreads in a prion-like manner between cells may guide novel therapeutic strategies for TDP-43-associated neurodegenerative diseases.Neurodegenerative disorders: Spread of misfolded protein aggregatesFurther research is needed to determine how an aggregate-forming protein common to several neurodegenerative disorders propagates throughout the brain. Many neurodegenerative conditions involve aggregates created by ‘prion-like’ proteins, misfolded proteins that can confer their abnormal structure on neighboring healthy proteins, resulting in aggregates which spread rather like an infection. Hyung-Jun Kim at the Korea Brain Research Institute in Daegu, South Korea, and co-workers reviewed current understanding of the transactive response DNA-binding protein 43 (TDP-43), an aggregate-forming protein implicated in disorders such as Alzheimer’s disease and frontotemporal dementia. Growing evidence suggests that TDP-43 may spread in a prion-like fashion. TDP-43 is implicated in the onset of Alzheimer’s, and the spread of misfolded TDP-43 aggregates is closely tied to disease severity. More research is needed into how TDP-43 propagates in different tissues and central nervous system cells.

Despite the impressive development of metal halide perovskites in diverse optoelectronics, progress on high-performance transistors employing state-of-the-art perovskite channels has been limited due to ion migration and large organic spacer isolation. Herein, we report high-performance hysteresis-free p-channel perovskite thin-film transistors (TFTs) based on methylammonium tin iodide (MASnI 3 ) and rationalise the effects of halide (I/Br/Cl) anion engineering on film quality improvement and tin/iodine vacancy suppression, realising high hole mobilities of 20 cm 2 V −1 s −1 , current on/off ratios exceeding 10 7 , and threshold voltages of 0 V along with high operational stabilities and reproducibilities. We reveal ion migration has a negligible contribution to the hysteresis of Sn-based perovskite TFTs; instead, minority carrier trapping is the primary cause. Finally, we integrate the perovskite TFTs with commercialised n-channel indium gallium zinc oxide TFTs on a single chip to construct high-gain complementary inverters, facilitating the development of halide perovskite semiconductors for printable electronics and circuits. Progress on high-performance transistor employing perovskite channels has been limited to date. Here, Zhu et al. report hysteresis-free tin-based perovskite thin-film transistors with high hole mobility of 20 cm 2 V –1 S –1 , which can be integrated with commercial metal oxide transistors on a single chip.

The Cox proportional hazards model commonly used to evaluate prognostic variables in survival of cancer patients may be too simplistic to properly predict a cancer patient’s outcome since it assumes that the outcome is a linear combination of covariates. In this retrospective study including 255 patients suitable for analysis who underwent surgical treatment in our department from 2000 to 2017, we applied a deep learning-based survival prediction method in oral squamous cell carcinoma (SCC) patients and validated its performance. Survival prediction using DeepSurv, a deep learning based-survival prediction algorithm, was compared with random survival forest (RSF) and the Cox proportional hazard model (CPH). DeepSurv showed the best performance among the three models, the c-index of the training and testing sets reaching 0.810 and 0.781, respectively, followed by RSF (0.770/0.764), and CPH (0.756/0.694). The performance of DeepSurv steadily improved with added features. Thus, deep learning-based survival prediction may improve prediction accuracy and guide clinicians both in choosing treatment options for better survival and in avoiding unnecessary treatments.

The mortality rates of COVID-19 vary across the globe. While some risk factors for poor prognosis of the disease are known, regional differences are suspected. We reviewed the risk factors for critical outcomes of COVID-19 according to the location of the infected patients, from various literature databases from January 1 through June 8, 2020. Candidate variables to predict the outcome included patient demographics, underlying medical conditions, symptoms, and laboratory findings. The risk factors in the overall population included sex, age, and all inspected underlying medical conditions. Symptoms of dyspnea, anorexia, dizziness, fatigue, and certain laboratory findings were also indicators of the critical outcome. Underlying respiratory disease was associated higher risk of the critical outcome in studies from Asia and Europe, but not North America. Underlying hepatic disease was associated with a higher risk of the critical outcome from Europe, but not from Asia and North America. Symptoms of vomiting, anorexia, dizziness, and fatigue were significantly associated with the critical outcome in studies from Asia, but not from Europe and North America. Hemoglobin and platelet count affected patients differently in Asia compared to those in Europe and North America. Such regional discrepancies should be considered when treating patients with COVID-19.

Background Cytoplasmic inclusions of transactive response DNA binding protein of 43 kDa (TDP-43) in neurons and astrocytes are a feature of some neurodegenerative diseases, such as frontotemporal lobar degeneration with TDP-43 (FTLD-TDP) and amyotrophic lateral sclerosis (ALS). However, the role of TDP-43 in astrocyte pathology remains largely unknown. Methods To investigate whether TDP-43 overexpression in primary astrocytes could induce inflammation, we transfected primary astrocytes with plasmids encoding Gfp or TDP - 43 - Gfp . The inflammatory response and upregulation of PTP1B in transfected cells were examined using quantitative RT-PCR and immunoblot analysis. Neurotoxicity was analysed in a transwell coculture system of primary cortical neurons with astrocytes and cultured neurons treated with astrocyte-conditioned medium (ACM). We also examined the lifespan, performed climbing assays and analysed immunohistochemical data in pan-glial TDP-43-expressing flies in the presence or absence of a Ptp61f RNAi transgene. Results PTP1B inhibition suppressed TDP-43-induced secretion of inflammatory cytokines (interleukin 1 beta (IL-1β), interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α)) in primary astrocytes. Using a neuron-astrocyte coculture system and astrocyte-conditioned media treatment, we demonstrated that PTP1B inhibition attenuated neuronal death and mitochondrial dysfunction caused by overexpression of TDP-43 in astrocytes. In addition, neuromuscular junction (NMJ) defects, a shortened lifespan, inflammation and climbing defects caused by pan-glial overexpression of TDP-43 were significantly rescued by downregulation of ptp61f (the Drosophila homologue of PTP1B) in flies. Conclusions These results indicate that PTP1B inhibition mitigates the neuronal toxicity caused by TDP-43-induced inflammation in mammalian astrocytes and Drosophila glial cells.

Chronic neuroinflammation is a common feature of the aged brain, and its association with the major neurodegenerative changes involved in cognitive impairment and motor dysfunction is well established. One of the most potent antiaging interventions tested so far is dietary restriction (DR), which extends the lifespan in various organisms. Microglia and astrocytes are two major types of glial cells involved in the regulation of neuroinflammation. Accumulating evidence suggests that the age-related proinflammatory activation of astrocytes and microglia is attenuated under DR. However, the molecular mechanisms underlying DR-mediated regulation of neuroinflammation are not well understood. Here, we review the current understanding of the effects of DR on neuroinflammation and suggest an underlying mechanistic link between DR and neuroinflammation that may provide novel insights into the role of DR in aging and age-associated brain disorders.

Underground space is becoming increasingly vulnerable to inundation owing to the enhanced likelihood and consequences of urban flooding. However, previous studies on flooding of underground space have paid little attention to how rainwater flows inside an underground space, what the optimal escape route might be, how much time would be required to escape, and how dangerous one specific area might be in comparison with another. This study investigated a method for assessing the spatiotemporal risk of flooding of an underground space considering both the flood intensity and the escape route. Two-dimensional hydrodynamic flow analysis was implemented to evaluate the flood intensity. Then, the shortest escape route was determined by applying the Dijkstra algorithm to the nodes and elements used in the 2D flow analysis. In addition, the risk of flooding in the underground space for a case without a water shield was compared with that determined for a case with an installed water shield.

Background The close association between bronchiectasis and nontuberculous mycobacterial pulmonary disease (NTM-PD) is well-known. However, the clinical impact of subsequent new-onset NTM-PD in bronchiectasis patients has not been elucidated. The aim of this study is to investigate the clinical courses and radiographic changes of patients with bronchiectasis in whom NTM-PD subsequently developed. Methods A total of 221 patients with bronchiectasis who had participated in a non-NTM bronchiectasis cohort between July 1st 2011 and August 31st 2019 at Seoul National University Hospital were included in this study. The data of patients in whom NTM-PD developed during this observation period were analyzed; specifically, changes in the Bronchiectasis Severity Index (BSI) and lesions on computerized tomography (CT) scan of the chest arising during the observation period. Results During the observation period, NTM was isolated from 35 patients. A total of 31 patients (14.0%) satisfied the diagnostic criteria of NTM-PD. The median time from enrollment in the cohort to the development of subsequent NTM-PD was 37 months (Interquartile range [IQR], 18–78 months). Mycobacterium avium complex was the most common pathogen (80.6%). Twelve patients underwent antibiotic treatment for NTM-PD with a median interval of 20 months (IQR, 13–30) from the time of NTM-PD diagnosis. When NTM-PD developed, the severity and extent of bronchiectasis, cellular bronchiolitis, and the extent of nodules worsened on CT scans, while BSI did not change. Conclusions NTM-PD can develop in previously negative bronchiectasis patients. It is associated with worsening radiographic lesions. Active screening of non-NTM bronchiectasis patients for new-onset NTM infection should be considered, especially if radiographic findings worsen. The BSI is not a reliable predictor of new-onset NTM-PD. Trial registration This study was performed at Seoul National University Hospital ( NCT01616745 ).

Background This study aimed to investigate the radiological changes in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) having bronchiolitis patterns on computed tomography (CT). Methods We retrospectively reviewed the final diagnosis and radiologic changes of patients suspected of having NTM-PD without cavity or bronchiectasis on CT image, between January 1, 2005 and March 31, 2021. NTM-PD was diagnosed based on the American Thoracic Society and Infectious Diseases Society of America criteria. The initial and final CT findings (bronchiectasis, cellular bronchiolitis, cavity formation, nodules, and consolidation) were compared between patients diagnosed with and without NTM-PD. Results This study included 96 patients and 515 CT images. The median CT follow-up duration was 1510.5 (interquartile range: 862.2–3005) days. NTM-PD was recognized in 43 patients. The clinical variables were not significantly different between patients with and without NTM-PD, except for underlying chronic airway disease ( P  < 0.001). Nodule and consolidation were more frequently observed on the initial CT scans of patients with NTM-PD compared with those without ( P  < 0.05). On the final follow-up CT scan, bronchiectasis ( P  < 0.001), cavity ( P  < 0.05), nodule ( P  < 0.05), and consolidation ( P  < 0.05) were more frequently observed in patients with NTM-PD. Among the 43 patients with NTM-PD, 30 showed a radiological progression on CT, with bronchiectasis ( n  = 22) being the most common finding. The incidence of bronchiectasis increased over time. Conclusion The bronchiolitis pattern on CT images of patients with NTM-PD showed frequent radiological progression during the follow-up period.

An indium arsenide quantum well with a ferromagnetic spin injector and a spin Hall detector is used to electrically measure the conductance oscillations due to spin precession in a transistor channel. The spin–orbit interaction in two-dimensional electron systems provides an exceptionally rich area of research. Coherent spin precession in a Rashba effective magnetic field 1 , 2 in the channel of a spin field-effect transistor 3 , 4 and the spin Hall effect 5 , 6 , 7 are the two most compelling topics in this area. Here, we combine these effects to provide a direct demonstration of the ballistic intrinsic spin Hall effect 8 and to demonstrate a technique for an all-electric measurement of the Datta–Das 3 conductance oscillation, that is, the oscillation in the source–drain conductance due to spin precession. Our hybrid device has a ferromagnet electrode as a spin injector and a spin Hall detector. Results from multiple devices with different channel lengths map out two full wavelengths of the Datta–Das oscillation. We also use the original Datta–Das technique with a single device of fixed length and measure the channel conductance as the gate voltage is varied. Our experiments show that the ballistic spin Hall effect can be used for efficient injection or detection of spin polarized electrons, thereby enabling the development of an integrated spin transistor.