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Background Restless legs syndrome (RLS), a neurological disorder, often affects sleep quality in hemodialysis patients. This study aimed to evaluate acupressure's effect on the severity of RLS symptoms and sleep quality in hemodialysis patients with RLS. Material and methods This study is a cluster-randomized crossover pilot study. Patients were randomized to two sequences: acupressure for one month and observation for another month (AC); and observation for one month and acupressure for another month (CA). For the four-week acupressure intervention, patients received 36 min of acupressure three times weekly during their hemodialysis sessions. The acupoints were on the bilateral lower limbs, including Zusanli (ST36), Yanglingquan (GB34), Sanyinjiao (SP6), Xuanzhong (GB39), Chengshan (BL57), and Taichong (LR3). RLS severity and sleep quality (measured with the Pittsburgh sleep quality index, PSQI) were measured at baseline, month 1, and month 2. Results AC sequence (n = 14) was similar to the CA sequence (n = 9) in terms of gender, age, education, employment, marital status, comorbid disease, BMI, duration of dialysis, medication for RLS and insomnia, RLS severity, and PSQI. The general linear mixed model revealed no significant carryover effect on RLS severity, PSQI, and the seven subscales of PSQI. A significant treatment effect (acupressure) was only observed in RLS severity (p = 0.0013) but not in PSQI and the seven subscales. The significant period effect was observed in RLS severity (p = 0.0250) and the subscale of sleep disturbance (p = 0.0021). Conclusion In hemodialysis patients with RLS, acupressure can alleviate the severity of RLS but cannot improve sleep quality.

Background: Plasma proteins are critical mediators of cardiovascular processes and are the targets of many drugs. Previous efforts to characterize the genetic architecture of the plasma proteome have been limited by a focus on individuals of European descent and leveraged genotyping arrays and imputation. Here we describe whole genome sequence analysis of the plasma proteome in individuals with greater African ancestry, increasing our power to identify novel genetic determinants. Methods: Proteomic profiling of 1301 proteins was performed in 1852 Black adults from the Jackson Heart Study using aptamer-based proteomics (SomaScan). Whole genome sequencing association analysis was ascertained for all variants with minor allele count ≥5. Results were validated using an alternative, antibody-based, proteomic platform (Olink) as well as replicated in the Multi-Ethnic Study of Atherosclerosis and the HERITAGE Family Study (Health, Risk Factors, Exercise Training and Genetics). Results: We identify 569 genetic associations between 479 proteins and 438 unique genetic regions at a Bonferroni-adjusted significance level of 3.8×10 -11 . These associations include 114 novel locus-protein relationships and an additional 217 novel sentinel variant-protein relationships. Novel cardiovascular findings include new protein associations at the APOE gene locus including ZAP70 (sentinel single nucleotide polymorphism [SNP] rs7412-T, β=0.61±0.05, P =3.27×10 -30 ) and MMP-3 (β=-0.60±0.05, P =1.67×10 -32 ), as well as a completely novel pleiotropic locus at the HPX gene, associated with 9 proteins. Further, the associations suggest new mechanisms of genetically mediated cardiovascular disease linked to African ancestry; we identify a novel association between variants linked to APOL1-associated chronic kidney and heart disease and the protein CKAP2 (rs73885319-G, β=0.34±0.04, P =1.34×10 -17 ) as well as an association between ATTR amyloidosis and RBP4 levels in community-dwelling individuals without heart failure. Conclusions: Taken together, these results provide evidence for the functional importance of variants in non-European populations, and suggest new biological mechanisms for ancestry-specific determinants of lipids, coagulation, and myocardial function.

Background This study was to perform an economic evaluation to understand clinical outcomes and health resource use between hip fracture patients receiving hospital-based postfracture fracture liaison service (FLS) care and those receiving usual care (UC) in Taiwan. Methods This cohort study included hospital-based data of 174 hip fracture patients who received FLS care (FLS group) from National Taiwan University Hospital, and 1697 propensity score-matched patients who received UC (UC group) of National Health Insurance claim-based data. Two groups had similar baseline characteristics but differed in hip fracture care after propensity score matching. Clinical outcomes included refracture-free survival (RFS), hip-refracture-free survival (HRFS), and overall survival (OS). Health resource use included inpatient, outpatient, and pharmacy costs within 2 years follow-up after the index of hip fracture. The economic evaluation of the FLS model was analyzed using the net monetary benefit regression framework based on the National Health Insurance perspective. Results The FLS group had longer RFS than the UC group, with an adjusted difference of 44.3 days (95% confidence interval: 7.2–81.4 days). Two groups did not differ in inpatient and outpatient costs during follow-up, but the FLS group had a higher expenditure than the UC group on osteoporosis-related medication. The probability of FLS being cost-effective was >80% and of increasing RFS, HRFS, and OS was 95%, 81%, and 80%, respectively, when the willingness-to-pay threshold was >USD 65/gross domestic product per day. Conclusion FLS care was cost-effective in reducing refracture occurrence days for patients initially diagnosed with hip fractures.

Objective This study was designed to observe the effect of electroacupuncture at Hegǔ (合谷LI4), or Houxī (后溪SI3) or Waiguān (外关TE5) acupoints on the function of the brain regions of a healthy human, and to explore the neural information mechanism of a specific connection between LI4 and the facial-oral area from the point of view of the brain function connection network. A further objective was to enrich knowledge of the specific connection between the body surface and the meridian route, and the specificity of acupoint effects. Methods A total of 30 healthy volunteers were randomly assigned to LI4, SI3, and TE5 groups. The members of each group were stimulated with electroacupuncture, and their heads were scanned using fMRI. DPARSFA 2.4 and REST 1.8 software were used for data preprocessing and statistical analysis. The paired t-test was used within group and the double sample t-test was used for two-group comparisons. Results In healthy people, left LI4 with electroacupuncture mainly caused a decrease of the functional connection of the right orofacial motor area of the brain, which remained decreased after removing the needle. When LI4 was compared with SI3 and TE5, LI4 caused a more significant decline in the functional connection of the right side of the brain during acupuncture. Conclusions Acupuncture at LI4 has a significant effect on the function of the face- and mouth-related areas in the brain, and there is a continuous effect. It is suggested that LI4 and the face and mouth have a specific relationship in the brain, which is most obvious during acupuncture.

Because of the energy crisis, companies started developing electric vehicles. Company A, as a new entrant, successfully developed a disruptive innovation of the world’s first high-performance, zero emissions, and two-wheeled electric scooter. As disruptive innovation is frequently discovered in the combination of different industrial technologies, company A is comprised of high-tech and traditional industry resources and knowledge. This study aims to explore the process of heterogeneous industry knowledge integration in the traditional motorcycle manufacturing industry by a case study of company A. Following qualitative research method, this study concludes four main findings in product development: (1) organizational knowledge integration is identified to mitigate the impact of functional conflict; (2) design validation knowledge integration is identified to set the standard for pioneer product strategy; (3) internal and external engineering knowledge integration is identified to realizes the goal of pioneer product strategy; (4) product validation knowledge integration is identified to coordinate the flexible planning process.

We present a CPU-based real-time cloth animation method for dressing virtual humans of various shapes and poses. Our approach formulates the clothing deformation as a high-dimensional function of body shape parameters and pose parameters. In order to accelerate the computation, our formulation factorizes the clothing deformation into two independent components: the deformation introduced by body pose variation (Clothing Pose Model) and the deformation from body shape variation (Clothing Shape Model). Furthermore, we sample and cluster the poses spanning the entire pose space and use those clusters to efficiently calculate the anchoring points. We also introduce a sensitivity-based distance measurement to both find nearby anchoring points and evaluate their contributions to the final animation. Given a query shape and pose of the virtual agent, we synthesize the resulting clothing deformation by blending the Taylor expansion results of nearby anchoring points. Compared to previous methods, our approach is general and able to add the shape dimension to any clothing pose model. Furthermore, we can animate clothing represented with tens of thousands of vertices at 50+ FPS on a CPU. We also conduct a user evaluation and show that our method can improve a user's perception of dressed virtual agents in an immersive virtual environment (IVE) compared to a realtime linear blend skinning method.

The proliferation of Internet of Things (IoT) applications has prompted the continuous increase of research efforts in recent years. In light of the diversified use cases and service requirements, the information freshness [or Age of Information (AoI)] of IoT data is key for latency-sensitive IoT applications (e.g., industrial automation and intelligent transportation) because stale information may lead to delayed responses and catastrophic outcomes. In addition, various types of IoT applications require the analytics of IoT data collected from their constituent IoT devices. While previous AoI-related works have analyzed or optimized the information freshness of various communication systems, the problem that the information cofreshness [or Coage of Information (CoI)] of an IoT application is determined by the maximum AoI of the constituent IoT devices has been rarely investigated. In this article, we address the grant assignment and transmission scheduling (GATS) problem for IoT and formulate it as an integer linear program (ILP) to minimize a weighted sum of CoI. Due to the intractability of the original GATS problem, we transform it to an equivalent problem of the maximization of the number of the eliminated age blocks. Then, we propose the CoI-aware age block elimination (CABEL) algorithm in which information updates are selected progressively according to their coage efficiency (CE) values and prove that the achieved approximation factor depends on the relative service costs and uplink delays. Our simulation results demonstrate that the proposed solution can effectively perform information updates and utilize service budgets, thereby achieving low CoI compared with the existing solutions under various parameter settings.

Traumatic brain injury (TBI) is a major public health challenge that is also the third leading cause of death worldwide. It is also the leading cause of long-term disability in children and young a...

Background: Cardiac hypertrophy is an important prepathology of, and will ultimately lead to, heart failure. However, the mechanisms underlying pathological cardiac hypertrophy remain largely unknown. This study aims to elucidate the effects and mechanisms of HINT1 (histidine triad nucleotide–binding protein 1) in cardiac hypertrophy and heart failure. Methods: HINT1 was downregulated in human hypertrophic heart samples compared with nonhypertrophic samples by mass spectrometry analysis. Hint1 knockout mice were challenged with transverse aortic constriction surgery. Cardiac-specific overexpression of HINT1 mice by intravenous injection of adeno-associated virus 9 (AAV9)–encoding Hint1 under the cTnT (cardiac troponin T) promoter were subjected to transverse aortic construction. Unbiased transcriptional analyses were used to identify the downstream targets of HINT1. AAV9 bearing shRNA against Hoxa5 (homeobox A5) was administrated to investigate whether the effects of HINT1 on cardiac hypertrophy were HOXA5-dependent. RNA sequencing analysis was performed to recapitulate possible changes in transcriptome profile.Coimmunoprecipitation assays and cellular fractionation analyses were conducted to examine the mechanism by which HINT1 regulates the expression of HOXA5. Results: The reduction of HINT1 expression was observed in the hearts of hypertrophic patients and pressure overloaded–induced hypertrophic mice, respectively. In Hint1 -deficient mice, cardiac hypertrophy deteriorated after transverse aortic construction. Conversely, cardiac-specific overexpression of HINT1 alleviated cardiac hypertrophy and dysfunction. Unbiased profiler polymerase chain reaction array showed HOXA5 is 1 target for HINT1, and the cardioprotective role of HINT1 was abolished by HOXA5 knockdown in vivo. Hoxa5 was identified to affect hypertrophy through the TGF-β (transforming growth factor β) signal pathway. Mechanically, HINT1 inhibited PKCβ1 (protein kinase C β type 1) membrane translocation and phosphorylation via direct interaction, attenuating the MEK/ERK/YY1 (mitogen-activated protein kinase/extracellular signal-regulated kinase kinase/yin yang 1) signal pathway, downregulating HOXA5 expression, and eventually attenuating cardiac hypertrophy. Conclusions: HINT1 protects against cardiac hypertrophy through suppressing HOXA5 expression. These findings indicate that HINT1 may be a potential target for therapeutic interventions in cardiac hypertrophy and heart failure.

Ali CMB Polarization Telescope (AliCPT) is the first Cosmic Microwave Background (CMB) polarimeter with a large focal plane camera to be deployed in the Northern Hemisphere, in the Tibetan Plateau. Here we present the design of a dichroic (90/150 GHz) focal plane camera capable of hosting up to 32,376 Transition-Edge Sensor (TES) bolometers operating from a base temperature of 280 mK. Detectors are fabricated as monolithic arrays of 1,704 feedhorn-coupled and polarization-sensitive TES bolometers that are packaged in independent modules and read out with a microwave multiplexing architecture. A custom RFSoC-based system manages the multiplexing readout. Prototype AliCPT pixels have been fabricated and characterized, demonstrating passband performance within 2.5% of design and cross-polarization systematic sensitivity $\leq$ 2%.

A support vector machine (SVM) is widely used for predicting the properties of fly ash blended concrete. However, the studies about the optimal design of fly ash blended concrete based on SVM are very limit. This study shows an SVM-based optimal design procedure of fly ash blended concrete. First, we built an SVM model and evaluated the compressive strength of fly ash blended concrete considering the effects of water to binder ratio, fly ash replacement ratio, and test ages. Second, we made parameter studies based on the SVM model. The parameter studies show that fly ash can improve the late age strength of concrete. This improvement is obvious for concrete with lower water to binder ratio. The optimal fly ash replacement ratio increases as the water to binder ratio decreases.

The satellite-based quantification of cloud radiative forcing remains poorly understood, due largely to the limitation or uncertainties in characterizing cloud-base height (CBH). Here, we use the CBH data from radiosonde measurements over China in combination with the collocated cloud-top height (CTH) and cloud properties from MODIS/Aqua to quantify the impact of CBH on shortwave cloud radiative forcing (SWCRF). The climatological mean SWCRF at the surface (SWCRFSUR), at the top of the atmosphere (SWCRFTOA), and in the atmosphere (SWCRFATM) are estimated to be −97.14, −84.35, and 12.79 W m−2, respectively for the summers spanning 2010 to 2018 over China. To illustrate the role of the cloud base, we assume four scenarios according to vertical profile patterns of cloud optical depth (COD). Using the CTH and cloud properties from MODIS alone results in large uncertainties for the estimation of SWCRFATM, compared with those under scenarios that consider the CBH. Furthermore, the biases of the CERES estimation of SWCRFATM tend to increase in the presence of thick clouds with low CBH. Additionally, the discrepancy of SWCRFATM relative to that calculated without consideration of CBH varies according to the vertical profile of COD. When a uniform COD vertical profile is assumed, the largest SWCRF discrepancies occur during the early morning or late afternoon. By comparison, the two-point COD vertical distribution assumption has the largest uncertainties occurring at noon when the solar irradiation peaks. These findings justify the urgent need to consider the cloud vertical structures when calculating the SWCRF which is otherwise neglected.

Background An early indicator for monitoring the effect of adjuvant treatment after lung cancer surgery is urgently needed. The study was to explore the effects of epithelial cell adhesion molecule (EpCAM) of circulating tumor cells (CTCs) in NSCLC patients with postoperative adjuvant chemotherapy. Methods Two drugs (platinum-containing chemotherapeutics + platinum-free chemotherapeutics) first-line chemotherapy regimen were given after surgery. MRNA of EpCAM was detected. Chest computed tomography, head computed tomography and abdominal B-ultrasound were reviewed before the first and third chemotherapy. Results EpCAM in CTCs from peripheral blood between the recurrent group and the non-recurrent group at 1 day before surgery, first, second and third adjuvant chemotherapy were no significant differences (P>0.05). Only one day before the fourth adjuvant chemotherapy treatment, it showed significant difference between the recurrent group and the non-recurrent group (P=0.008). There was a significant difference between the time of imaging diagnosis of recurrence or metastasis and the time of monitoring the expression level of EpCAM in CTCs from peripheral blood (P

Background/Purpose: Recent study suggested that type 2 diabetes (T2DM) attributed to body mass index (BMI) could be influenced by liver aminotransferase. We aim to ascertain the cut-off point of BMI associated with T2DM and the influence of both elevated aminotransferase (AST) and alanine aminotransferase (ALT). Materials and Methods: In our retrospective cohort study, T2DM was diagnosed when FBS ≥ 7.0 mmol/L, BMI of participants with baseline fasting (FBS) < 7.0 mmol/L was divided by percentiles and by aminotransferanse (ALT and AST ≥ 20 U/L, ALT or AST < 20 U/L). Hazard ratios and the turning point of BMI of high T2DM risk was estimated in totality and different aminotransferanse groups. Results: During an average follow-up time of 3.71 years of 33346 participants, 1486 developed T2DM, and the average baseline BMI of participants who developed T2DM was 26.22 kg/m2. Cumulative incidence of T2DM was more than 5% when ALT and AST ≥ 20U/L, age over 44, male sex or BMI over 25.39 kg/m2; The risk of T2DM incidence increased as the BMI grow. The turning point of BMI at high risk of T2DM was 25.0 kg/m2 in totality, 25.1 kg/m2 when ALT or AST < 20 U/L and 26.1 kg/m2 when ALT and AST ≥ 20U/L. Conclusions: BMI of 25.0 kg/m2 was the cutoff point for T2DM development, and there is greater association between BMI and T2DM when ALT or AST < 20 U/L.

This letter investigates the resource allocation problem for multiple Unmanned Aerial Vehicles (UAVs)-served Machine-to-Machine (M2M) communications. Our goal is to maximize the sum-rate of UAVs-served M2M communications by jointly considering the transmission power, transmission mode, frequency spectrum, relay selection and the trajectory of UAVs. In order to model the uncertainty of stochastic environments, we formulate the resource allocation problem to be a Markov game, which is the generalization of Markov Decision Process (MDP) for the case of multiple agents. However, owning to the UAVs mobility poses the difficulty of perceiving the environment, we propose a Long Short-Term Memory (LSTM) with Generative Adversarial Networks (GANs) framework to better track and forecast the UAVs mobility and improving the network reward. Numerical results demonstrate that the proposed framework outperforms the conventional LSTM and Deep Q-Network (DQN) algorithms.

This study was undertaken to assess the modulating effects of (1) pre-exposure to repeated social disruption and (2) group testing on writhing associated with visceral pain induced by intraperitoneal administration of acetic acid. Six consecutive days of social disruption were used to prime for stress, while group testing referred to 3 mouse cage-mates receiving the acetic acid–induced writhing test as a group. Social disruption–induced stress-pre-exposed mice displayed a greater number acid-induced writhes compared to mice not receiving the pre-exposure. However, mice displayed fewer acid-induced writhes in a triad group vs. individually, suggesting group-mediated writhing-reducing effects. Likewise, group testing prevented the stress pre-exposure escalation in acid-induced writhes. Additional studies revealed that the stress-pre-exposed mice had increased expression in accumbal TRPV1 receptors. Systemic (0.25 mg/kg) and bilateral intra-accumbal (0.2 ng/0.2 µl/side) administration of SB366791, a TRPV1 receptor antagonist, reliably prevented the stress pre-exposure escalation in acid-induced writhing; SB366791 treatment alone did not affect acid-induced writhing, stress pre-exposure anxiety-like behavior, or the group testing effects. Furthermore, lower neuronal activation was found in the medial septal nucleus in group vs. individual tested mice. Intra-medial septum (0.2 µg/0.5 µl) infusion with bicuculline, a GABAA receptor antagonist, effectively prevented group-mediated writhing-reducing effects, but not individual acid-induced writhing effects. These findings suggest that social disruption–induced stress pre-exposure may upregulate accumbal TRPV1 receptor expression and consequently aggravate acid-induced writhing. Group testing prevents such stress pre-exposure escalation of acid-induced writhing most likely by strengthening the GABAergic inhibition on local neural activity in the medial septum.

BackgroundENABLE (Educate, Nurture, Advise, Before Life Ends) is a nurse coach-led, early palliative care model for patients with advanced cancer and their family caregivers. Content covered includes problem-solving, advance care planning, symptom management and self-care. The aim was to evaluate the cultural acceptability of ENABLE among patients with advanced cancer and their caregivers in Singapore and identify modifications for an adapted ENABLE-SG model.MethodsQualitative formative evaluation with a thematic analysis approach in two hospitals in Singapore, involving patients (n = 10), family caregivers (n = 11) and healthcare professionals (n = 10) who care for patients with advanced cancer. Semi-structured interviews were conducted to explore (i) the main needs and challenges facing individuals with advanced cancer and their family caregivers; (ii) patient involvement in healthcare decision making; and (iii) content and delivery of ENABLE.ResultsWhile physical needs were largely well met, participants expressed that psychosocial care was delivered too late in the illness trajectory. Healthcare decision making approaches varied from a patient-centred shared decision-making model to a family-centred model where patients may not know their cancer diagnosis and prognosis. The content was considered to be relevant, comprehensive and practical; financial assistance, adjustment to body image, and evaluation of complementary therapy were also recommended. Face-to-face rather than telephone sessions were preferred to facilitate rapport building.ConclusionsENABLE was broadly acceptable with some modifications, including adjusting the content to ensure it can be delivered even if the patient is not fully aware of cancer diagnosis and delivering the first session face-to-face with flexibility for subsequent sessions.

The rapid growth of traffic demand and innovation of mobile networks have pushed the current communication infrastructure to provide a tight integration of different wireless technologies. On the one hand, all user connections are expected to be heterogeneous in future networks and thus an intelligent mobility management is essential to satisfy the requirements of lower latency, less power consumptions and last but not least possible uninterrupted ongoing session when a User Equipment (UE) moves across network boundaries. On the other hand, Device-to-Device (D2D) communication as a revolutionary technology to enhance network performance has shown a great potential in dominating future communication market. Consequently, in this paper, we investigate the mobility management problem for D2D communications in heterogeneous networks. We leverage on IEEE 802.21 Media Independent Service (MIS) and propose a new framework, so-called enhanced version of IEEE 802.21 MIS that supports D2D communication (E-MIS-D2D) to enhance D2D mobility experience over heterogeneous networks. The E-MIS-D2D is a network assisted and initiated architecture, in which a load-aware mode selection algorithm is also proposed for selecting the transmission mode between D2D and non-D2D modes. Through extensive simulations, we validate that the proposed method outperforms the existing methods in terms of packet loss ratio, average throughput, latency, bandwidth usage and load rate of eNB.

Sustainable concrete which contains fly ash and slag is increasingly used in modern construction practices. This study presents a genetic algorithm (GA) assisted artificial neural network (ANN) model for evaluating the compressive strength of sustainable concrete. 425 mixtures are used for making the prediction system. Genetic algorithm (GA) is used to generate the initial values of the weight matrix and bias of ANN. The input parameter of GA assisted ANN is water-to-binder ratio, fly ash or slag replacement ratio, sand ratio, and water contents. The output result is compressive strength. The correlation coefficients for single ANN and GA assisted ANN model are 0.88 and 0.911, respectively. GA assisted ANN model has a strong prediction ability for the strength of sustainable concrete.

Fly ash is widely used for replacing partial cement and producing high-performance concrete. The concrete production company is interested in the optimal substitute ratio of fly ash. This study presents a general procedure for evaluating the optimal substitute ratio of fly ash. First, the compressive strength of fly ash blended concrete is evaluated based on adaptive neuro-fuzzy inference system (ANFIS). The water-to-binder ratio, fly ash replacement ratio, and ages are used as input parameters of ANFIS. Strength is the output parameter of ANFIS. Second, sensitivity analysis is performed using ANFIS. The development of relative strength of fly ash blended concrete is calculated considering water-to-binder ratio, fly ash replacement ratio, and ages. The analysis results show that the optimal replacement fly ash is dependent on water-to-binder ratio of concrete. As thewater-to-binder ratio decreases from 0.5 to 0.3, the optimal substitute ratio of fly ash increases from 15% to 30%.

BackgroundCurrent incidence and outcome of patients with acute hypoxaemic respiratory failure requiring mechanical ventilation in the intensive care unit (ICU) are unknown, especially for patients not meeting criteria for acute respiratory distress syndrome (ARDS).MethodsAn international, multicentre, prospective cohort study of patients presenting with hypoxaemia early in the course of mechanical ventilation, conducted during four consecutive weeks in the winter of 2014 in 459 ICUs from 50 countries (LUNG SAFE). Patients were enrolled with arterial oxygen tension/inspiratory oxygen fraction ratio ≤300 mmHg, new pulmonary infiltrates and need for mechanical ventilation with a positive end-expiratory pressure of ≥5 cmH2O. ICU prevalence, causes of hypoxaemia, hospital survival and factors associated with hospital mortality were measured. Patients with unilateral versus bilateral opacities were compared.Findings12 906 critically ill patients received mechanical ventilation and 34.9% with hypoxaemia and new infiltrates were enrolled, separated into ARDS (69.0%), unilateral infiltrate (22.7%) and congestive heart failure (CHF; 8.2%). The global hospital mortality was 38.6%. CHF patients had a mortality comparable to ARDS (44.1% versus 40.4%). Patients with unilateral-infiltrate had lower unadjusted mortality, but similar adjusted mortality compared to those with ARDS. The number of quadrants on chest imaging was associated with an increased risk of death. There was no difference in mortality comparing patients with unilateral-infiltrate and ARDS with only two quadrants involved.InterpretationMore than one-third of patients receiving mechanical ventilation have hypoxaemia and new infiltrates with a hospital mortality of 38.6%. Survival is dependent on the degree of pulmonary involvement whether or not ARDS criteria are reached.

Gastroesophageal variceal bleeding is a severe complication of cirrhotic portal hypertension. Endoscopic treatment is recommended as the first-line therapy for gastroesophageal variceal bleeding, and its therapeutic effect is closely related to the visualization of endoscopy. We reported 2 cases of gastric variceal bleeding in which clear endoscopic visualization was obtained with two simple approaches assisted by suction tube and stone retrieval basket, respectively. Endoscopic treatments were successfully conducted after the removal of giant blood clots. Serious complications were not found.

Rationale: Patients with and without cardiovascular diseases have been shown to be at risk of influenza-mediated cardiac complications. Recent clinical reports support the notion of a direct link between laboratory-confirmed influenza virus infections and adverse cardiac events. Objective: Define the molecular mechanisms underlying influenza virus–induced cardiac pathogenesis after resolution of pulmonary infection and the role of necroptosis in this process. Methods and Results: Hearts from wild-type and necroptosis-deficient (MLKL [mixed lineage kinase domain-like protein]-KO) mice were dissected 12 days after initial influenza A virus (IAV) infection when viral titers were undetectable in the lungs. Immunofluorescence microscopy and plaque assays showed presence of viable IAV particles in the myocardium without generation of interferon responses. Global proteome and phosphoproteome analyses using high-resolution accurate mass-based LC-MS/MS and label-free quantitation showed that the global proteome as well as the phosphoproteome profiles were significantly altered in IAV-infected mouse hearts in a strain-independent manner. Necroptosis-deficient mice had increased survival and reduced weight loss post-IAV infection, as well as increased antioxidant and mitochondrial function, indicating partial protection to IAV infection. These findings were confirmed in vitro by pretreatment of human and rat myocytes with antioxidants or necroptosis inhibitors, which blunted oxidative stress and mitochondrial damage after IAV infection. Conclusions: This study provides the first evidence that the cardiac proteome and phosphoproteome are significantly altered post–pulmonary influenza infection. Moreover, viral particles can persist in the heart after lung clearance, altering mitochondrial function and promoting cell death without active replication and interferon responses. Finally, our findings show inhibition of necroptosis or prevention of mitochondrial damage as possible therapeutic interventions to reduce cardiac damage during influenza infections. Graphic Abstract: A graphic abstract is available for this article.

Background and aims Recent genome-wide association studies have shown that low-density lipoprotein receptor (LDLR) rs1433099 polymorphism is associated with cardiovascular disease (CVD) risk in many countries. However, the association of LDLR rs1433099 with CVD in China has not been reported yet. There are no studies on LDLR rs1433099 and non-alcoholic fatty liver disease (NAFLD) as well. The purpose of this study was to investigate whether LDLR rs1433099 is related to CVD or NAFLD in the Chinese population. Methods LDLR rs1433099 polymorphism was genotyped in 507 individuals, including 140 healthy controls, 79 NAFLD patients, 185 CVD patients, and 103 patients with NAFLD combined with CVD. The expression of LDLR was tested by the sequence detection system, and clinical parameters were assessed by biochemical tests and physical examination. Results The genotype distribution of LDLR rs1433099 was not statistically different among the NAFLD group, the CVD group, the combined group, and the healthy control group (p>0.05). There was no significant correlation of LDLR rs1433099 genotypic distribution or allele frequency and the risk of NAFLD, CVD or NAFLD combined with CVD (p>0.05). In the CVD group, T allele carriers had higher alkaline phosphatase and gamma-glutamyl transpeptidase than non-carriers (p Conclusions Our study demonstrated that the LDLR rs1433099 polymorphism is not a risk factor of NAFLD. The LDLR rs1433099 polymorphism may increase the risk of CVD through a mechanism involving alkaline phosphatase and gamma-glutamyl transpeptidase.

Background This randomized clinical trial aimed to compare the preparation time and severity of postoperative pain between HyFlex Electric Discharge Machine (EDM) glide path file (GPF) and PathFile. Methods Eighty patients whose molar teeth had at least one severely curved canal were treated by the same specialist. After access cavity preparation, the patients were randomly assigned to receive glide path enlargement with either HyFlex EDM GPF or PathFile. ProTaper Next X1 and X2 files were used to prepare the canals. The time of preparation was assessed and the severity of postoperative pain over the next 7 days was recorded. The preparation time and the postoperative pain scores were compared using the Linear Mixed Models (P ≤ 0.05). Results Glide path enlargement time was significantly shorter with HyFlex EDM GPF (27.828 ± 2.345 s) than with PathFile (48.942 ± 2.864 s) (P P Conclusions Postoperative pain and glide path preparation time could be reduced by using HyFlex EDM GPF system. Trial registration PKUSSNCT, PKUSSNCT-17B12, Registered 24 October 2017.

Script is the structured knowledge representation of prototypical real-life event sequences. Learning the commonsense knowledge inside the script can be helpful for machines in understanding natural language and drawing commonsensible inferences. Script learning is an interesting and promising research direction, in which a trained script learning system can process narrative texts to capture script knowledge and draw inferences. However, there are currently no survey articles on script learning, so we are providing this comprehensive survey to deeply investigate the standard framework and the major research topics on script learning. This research field contains three main topics: event representations, script learning models, and evaluation approaches. For each topic, we systematically summarize and categorize the existing script learning systems, and carefully analyze and compare the advantages and disadvantages of the representative systems. We also discuss the current state of the research and possible future directions.

Background The pandemic of SARS-CoV-2 (COVID-19), which began in December 2019, spread mostly from person to person through respiratory droplets. A recommendation was issued to postpone all elective surgical practices. However, some confirmed or suspected COVID-19 patients required life-saving emergent surgeries. Methods To facilitate emergent surgical interventions for these patients, we have reviewed the current literature and established an algorithm of precautions to be taken by operating room team members during the COVID-19 pandemic. Results The initial algorithm of preparation for surgical intervention during the COVID-19 pandemic was relatively simple. However, the abrupt increase of confirmed COVID-19 cases due to returned overseas travelers since mid-March 2020 disrupted the routine hospital clinical service. Due to the large number of febrile patients, the algorithm was therefore revised according to travel history, occupation, contact and cluster history (TOCC), unexplained fever/symptoms, and emergent/nonemergent surgery. TOCC (+) patients presenting with otherwise unexplained fever/symptoms would be regarded as belonging to the fifth category of "severe special infectious pneumonia." If the patient requires emergent surgery to relieve the non-life-threatening disorders, two times of negative COVID-19 tests are necessary before the operation is approved. For life-threatening situations without two negative results of COVID-19 tests, the operation schedule should be approved by the Chairman of Surgery Management Committee. Conclusion The application of a clear and integrated algorithm for operating room team members aids in effective personal protective equipment facilitation to keep both healthcare providers and patients safe as well as to prevent hospital-based transmission of COVID-19.

Background Neutrophil-lymphocyte count ratio (NLCR) has been reported as better indicator of bacteremia than procalcitonin (PCT), and more precise predictor of mortality than C-reactive protein (CRP) under various medical conditions. However, large controversy remains upon this topic. To address the discrepancy, our group has compared the efficiency of NLCR with conventional inflammatory markers in predicting the prognosis of critical illness. Methods We performed a multi-center retrospective cohort study involving 536 ICU patients with outcomes of survival, 28- and 7-day mortality. NLCR was compared with conventional inflammatory markers such as PCT, CRP, serum lactate (LAC), white blood cell, neutrophil and severity score APACHE II (Acute Physiology and Chronic Health Evaluation II) to evaluate the potential outcomes of critical illness. Then, receiver operating characteristics (ROC) curves were constructed to assess and compare each marker’s sensitivity and specificity respectively. Results NLCR values were not different between survival and mortality groups. Meanwhile, remarkable differences were observed upon APACHE II score, CRP, PCT and LAC levels between survival and death groups. ROC analysis revealed that NLCR was not competent to predict prognosis of critical illness. The AUROCs of conventional markers such as CRP, PCT, LAC and APACHE II score were more effective in predicting 28- and 7-day mortality. Conclusions NLCR is less reliable than conventional markers CRP, PCT, LAC and APACHE II score in assessing severity and in predicting outcomes of critical illness.

Whirling has been adopted for the cost-effective machining of blade-shape components in addition to traditional end milling and flank milling processes. To satisfy the requirements of rotary forming in the blade whirling process, the workpiece must be clamped at both ends in suspension and rotated slowly during machining, which complicates the dynamics. This study aims to identify the dynamic characteristics within the blade whirling operation and present strategies for stability prediction. In this study, the dynamic characteristics of a whirling system are modeled by assuming symmetric and asymmetric parameters. Theoretical prediction frequency response function (FRF) results are compared with experimental results. Moreover, semi-discretization stability lobe diagrams (SLDs) obtained using the dynamic parameters of these models are investigated experimentally. The results show that the asymmetric model is more suitable for describing the whirling system, whereas the symmetric model presents limitations associated with the frequency range and location of measuring points. Finally, a set of airfoil propeller blade whirling operations is conducted to verify the prediction accuracy.

Optical nanothermometers have attracted much attention due to their non-contact and precise measurement with high spatial resolution at the micro- and nanoscales. They can be applied in various fields such as micro-opto-electronics, photonics, and biomedical thermal and pH sensing, while most thermal sensors reported so far contain heavy metals or have low sensitivity. Herein, we demonstrate a highly sensitive ratiometric thermal sensor based on colloidal C-dots. C-dots exhibit dual emission originating from the band gap emission and surface-dominant emission, which show a different temperature-dependent photoluminescence (PL) response. Among different surface-functionalized C-dots, C-dots@OH exhibit an absolute thermal sensitivity of -0.082 °C-1, which is the highest among various types of ratiometric thermosensors, making it a very promising candidate for high-sensitivity, self-calibrated nanoscale thermometry. As a proof-of-concept, C-dots@OH were employed to monitor the intracellular temperature (32-42 °C), showing a clear trend for temperature variation in a single cell, indicating that C-dots could offer a powerful tool for a potential precise measurement of the intracellular temperature. They could also be used as thermal sensors for nano-electronic and optoelectronic devices.

It has been suggested that immunogenic cell death (ICD) has therapeutic potential; however, its anticancer immunity is considerably hampered by the in situ immunosuppressive microenvironment within the tumor area, such as the dysfunction of antigen-presenting cells. Herein, we present an in vitro ICD-inducing modality to circumvent such impairment of immune activation. To this end, a "hot", i.e., immunogenic, whole tumor cell vaccine is generated in vitro and subcutaneously vaccinated in the normal tissue, departing from the site of the in situ immunosuppressive tumor area, to fully leverage the ICD-inducing antitumor immunity. In particular, the immunogenic dying tumor cells, caged by cellular disulfide-thiol exchange, are mediated by photoactivation. After subcutaneous vaccination, the photoactivated caged live cell vaccine (CLCV) exerts multi-durable immunostimulatory property, which, when adjuvanted by CpG, efficiently promotes dendritic cell (DC) activation and elicits robust CD8+ T-cell responses in vivo. Importantly, the generated T-cell responses are shown to protect 75% mice preimmunized with CLCV against tumor initiation and significantly retards tumor growth in the therapeutic setting. The strategy presented here may help to enrich the current vaccine design for cancer immunotherapy.

Reliability is a critical factor in designing of wireless body area networks. In this letter, we propose a resource scheduling strategy and solving an optimization problem to maximize the reliability of the transmission of emergency-critical sensory data. We jointly consider transmission mode, relay selection, time slot allocation, and transmit power of each body sensor and formulating the scheduling problem to be a Markov decision process. In this strategy, the scheduling decision is made by each body sensor that do not have complete and global network information. Owning to the formulated problem is nonconvex and the high computation complexity, we propose a deep reinforcement learning algorithm to solve the problem. Numerical results reveal that the proposed strategy is capacity of guaranteeing the reliability of transmission with an acceptable convergence speed.

In recent years, e-sports has rapidly developed, and the industry has produced large amounts of data with specifications, and these data are easily to be obtained. Due to the above characteristics, data mining and deep learning methods can be used to guide players and develop appropriate strategies to win games. As one of the world's most famous e-sports events, Dota2 has a large audience base and a good game system. A victory in a game is often associated with a hero's match, and players are often unable to pick the best lineup to compete. To solve this problem, in this paper, we present an improved bidirectional Long Short-Term Memory (LSTM) neural network model for Dota2 lineup recommendations. The model uses the Continuous Bag Of Words (CBOW) model in the Word2vec model to generate hero vectors. The CBOW model can predict the context of a word in a sentence. Accordingly, a word is transformed into a hero, a sentence into a lineup, and a word vector into a hero vector, the model applied in this article recommends the last hero according to the first four heroes selected first, thereby solving a series of recommendation problems.

Background Cardiac injury in patients with coronavirus disease 2019 (COVID-19) has been reported in recent studies. However, reports on the risk factors for cardiac injury and their prognostic value are limited. Results In total, 15.9% of all cases were defined as cardiac injury in our study. Patients with severe COVID-19 were significantly associated with older age and higher respiratory rates, Sequential Organ Failure Assessment (SOFA) scores, cardiac injury biomarkers and PaO2/FiO2 ratios. Male patients with chest distress and dyspnea were more likely to have severe disease. Patients with cardiac injury were significantly more likely to have a severe condition and have an outcome of death. However, no significant difference was found in respiratory rates, dyspnea or PaO2/FiO2 ratio between patients with or without cardiac injury. In the logistic regression model, pre-existing hypertension and higher SOFA score were independent risk factors for patients with COVID-19 developing cardiac injury. Conclusions Our study revealed that cardiac injury was an important predictor for patients having a severe or fatal outcome. Patients with pre-existing hypertension and higher SOFA scores upon admission were more likely to develop cardiac injury. Nevertheless, pulmonary ventilation dysfunction and oxygen inhalation insufficiency were not the main causes of cardiac injury in patients with COVID-19. Methods A total of 113 confirmed cases were included in our study. Severe patients were defined according to American Thoracic Society guidelines for community-acquired pneumonia. Cardiac injury was defined as a serum cTnI above the 99th-percentile of the upper reference limit. Patient characteristics, clinical laboratory data and treatment details were collected and analyzed. The risk factors for patients with and without cardiac injury were analyzed.

Immunotherapy techniques, such as immune checkpoint inhibitors, chimeric antigen receptor (CAR) T cell therapies and cancer vaccines, have been burgeoning with great success, particularly for specific cancer types. However, side effects with fatal risks, dysfunction in tumor microenvironment and low immune response rates remain the bottlenecks in immunotherapy. Nano metal-organic frameworks (nMOFs), with an accurate structure and a narrow size distribution, are emerging as a solution to these problems. In addition to their function of temporospatial delivery, a large library of their compositions, together with flexibility in chemical interaction and inherent immune efficacy, offers opportunities for various designs of nMOFs for immunotherapy. In this review, we overview state-of-the-art research on nMOFs-based immunotherapies as well as their combination with other therapies. We demonstrate that nMOFs are predominantly customized for vaccine delivery or tumor-microenvironment modulation. Finally, a prospect of nMOFs in cancer immunotherapy will be discussed.

Scientific knowledge contribution to online knowledge-sharing platforms has long been regarded as instrumental behavior based on utilitarian considerations. Employing cognitive evaluation theory, this study examines scientific expert users’ behavioral metrics to understand the factors responsible for users continuing to contribute their scientific knowledge for an extended period or a very short span. We found that expert users’ intrinsic motivations, which has received little attention in recent studies, constitute an important indicator of sustained online scientific knowledge contribution. Furthermore, although social rewards fail to predict the continuity of scientific knowledge contribution, they prolong the duration of knowledge contribution by enhancing the intrinsic motivations of expert users. In conclusion, a self-reinforcement mechanism underlies the relationship of intrinsic motivation with social rewards, which governs continuous online scientific knowledge contribution behavior.

After sternal tumor resection, reconstruction of chest wall defects is still a challenging part of thoracic surgery. Three‐dimensional (3D)‐printed titanium alloy prosthesis implants provide an effective solution. The bionic bone trabecular micropore structure, which is beneficial to the human body, increases stability and robustness of the prosthesis. Here, we report a successful case of a customized prosthesis using a 3D‐printed titanium alloy to repair and reconstruct bone defects in a patient with sternal osteosarcoma who underwent radical resection of the whole sternum., We report a successful case of a customized prosthesis using a 3D‐printed titanium alloy to repair and reconstruct bone defects in a patient with sternal osteosarcoma who underwent radical resection of the whole sternum.

With the booming development of smartphones in our daily lives, the integration of advanced medical technologies and mobile health (mHealth) to manage disease has become an irresistible trend. To extend quality tumour treatment into our daily lives, an mHealth platform was developed by using ferroelectric BiFeO3 nanomaterials (BFO) modified with TAT peptide (TAT-BFO) and a smartphone-controlled wearable device. With the control of a wearable device, TAT-BFO could be enriched in tumour site via magnetic targeting, and then triggered to generate reactive oxygen species (ROS) for efficient tumour therapy through temperature fluctuation. In both murine orthotopic breast tumour and resectable breast tumour models, this mHealth platform was demonstrated to inhibit tumour growth and prevent tumour recurrence significantly. Moreover, the transcriptomics and multiphysics simulation analysis further elucidated the working mechanism of the mHealth platform. This mHealth platform exhibits great potential for guiding daily-treatment and simplifying clinical treatment of tumours.

BackgroundMacrolides have been widely used to treat moderate-to-severe acne for more than 50 years. However, the prevalent antibiotic resistance of Propionibacterium acnes, along with the absence of clinically available resistance tests, has made macrolide misuse a frequent occurrence around the globe, with serious consequences.ObjectiveWe developed Cutibacterium acnes quantitative PCR (qPCR)-based antibiotics resistance assay (ACQUIRE) to enable fast and accurate detection of C. acnes macrolide resistance in clinical settings, representing an opportunity to administer antibiotics more wisely and improve the quality of care.MethodsA cross-sectional observational study (n = 915) was conducted to probe into the macrolide resistance of C. acnes in patients with acne.ResultsThe high sensitivity of ACQUIRE enabled us to reveal a much higher C. acnes 23S recombinant DNA (rDNA) point mutation rate (52%) and thus a higher macrolide resistance (75.5%) compared to previous reports. Carriage of ermX gene was discovered on 472 (53%) subjects, which concurs with previous studies.ConclusionThe macrolide resistance of C. acnes is much higher than previously reported. Integrating ACQUIRE into acne treatment modalities may eliminate macrolide misuse and achieve better clinical improvements.

Purpose Emerging studies have revealed that platelets are involved in tumor metastasis in lung adenocarcinoma (ADC). The solid pathological subtype of lung ADC is associated with metastasis, recurrence, and poor prognosis. However, there is no study exploring the relationship between platelets and different lung pathological subtypes. Patients and Methods The association between platelet counts and lymph node metastasis was analyzed in 852 patients with lung ADC who underwent surgery and lymph node dissection. Multivariate logistic analysis was conducted to identify the risk factors of lymph node metastasis. Then, lymph node metastasis and other factors were analyzed to determine their correlation with platelet count and histological subtype. Results We found that the platelet count was associated with lymph node metastasis (P = 0.01) in multivariable analysis, independent of tumor size, predominant subtype, visceral pleural invasion, and microvessel invasion. In patients with a platelet count ≥300 × 109/L, the rate of lymph node metastasis was 38.5%, almost twice as high as that in patients with a platelet count

Idiopathic pulmonary fibrosis (IPF) may present comorbid obstructive lung diseases with small airway dysfunction (SAD). Existing guidelines suggest that inhaled bronchodilators should be used if the ratio of forced expiratory volume in the 1st second and forced vital capacity (FEV1/FVC) 1/FVC > 0.7 even with coexisting emphysema. We retrospectively enrolled IPF patients who were registered at our outpatient clinic. At baseline, 63 patients completed computed tomography (CT) scans, lung function measurements, and symptom questionnaires. Among these patients, 54 (85.71%) underwent antifibrotic treatment and 38 (60.32%) underwent long-acting bronchodilator treatment. The median FEV1/FVC was 0.86. Not all patients treated with bronchodilators showed significant changes in lung function. IPF patients with SAD, determined by IOS parameters, showed significant improvement in FEV1, FEF25–75%, and symptom scores after bronchodilator treatment. Bronchodilator efficacy was not observed in patients without SAD. CT-confirmed emphysema was seen in 34.92% of patients. There were no changes in lung function or symptom scores after bronchodilator treatment in patients with emphysema. In conclusion, FEV1/FVC cannot reflect the airflow limitation in IPF. Emphysema in IPF is not a deciding factor in whether patients should receive bronchodilator treatment. IOS parameters may be useful to guide bronchodilator therapy in patients with IPF coexisting with SAD.

Canine melanoma is a malignant tumour that exhibits aggressive behaviour, and frequently metastasizes to regional lymph nodes and distant sites. Currently, there are no effective treatments or practical prognostic biomarkers for canine melanoma. The enzyme kynurenine 3-monooxygenase (KMO), which plays a central role in the tryptophan metabolism, has previously been identified as the main pathogenic factor in neurodegenerative diseases; however, it has recently been found to be positively associated with tumour malignancy in human hepatocellular carcinoma and canine mammary tumours. Signal transducer and activator of transcription 3 (STAT3) is a well-known oncoprotein contributing to the proliferation, survival, invasiveness and metastasis of a variety of cancers. Although whether STAT3 and KMO collaborate in tumorigenesis needs to be further verified, our previous findings showed that inhibition of KMO activity reduced activation of STAT3. This study investigated the expressions of KMO and STAT3/phosphorylated (pSTAT3) by immunohistochemical analysis in 85 cases of canine melanoma, showing their expression levels were high within highly mitotic melanoma cells. KMO Overexpression was significantly associated with increased STAT3 and pSTAT3 expressions. Melanoma tissues with higher KMO, STAT3 and pSTAT3 protein expressions were correlated with reduced survival rates of the canine patients. Moreover, inhibition of KMO activity in canine melanoma cells resulted in reduced cell viability, in addition to decreased expressions of STAT3 and pSTAT3. Our results indicated the significance of KMO and the potential role of KMO/STAT3 interaction in enhancing tumour development. Additionally, KMO and STAT3/pSTAT3 may be viewed as useful biomarkers for the prediction of prognosis of canine melanoma.

Background. Caregivers experience a number of challenges when caring for a chronically ill patient which can affect their physical, emotional and psychological health. Aim. To assess caregiver burden and its relationship to health-related quality of life among primary caregivers of patients with long-term illness in the community. Methods. A cross-sectional study using caregiver burden scale and SF-36 Survey on thirty-two caregivers of patients with long-term illness under a community health centre in Brunei from January to March 2019. Findings. Caregiver burden was highest for general strain, isolation and disappointment. Increased age of caregiver was significantly associated with reduced physical functioning. Male caregivers had significantly higher role functioning while female caregivers had significantly higher social functioning role. Increased caregiver burden showed decreased overall health-related quality of life. Conclusions. Caregiver burden should not be disregarded in patient treatment plan. Clinicians and relevant authorities should collaborate care plans with primary caregivers accounting for both patient and caregiver well-being. More detailed qualitative studies should be done to provide a better insight on caregiver burden.

Background Cholangiocarcinoma (CCA) is a malignant cancer of the biliary tract with a poor prognosis. Herein, we investigated possible mechanism of extrahepatic CCA (eCCA) by dysregulated iron metabolism and post-translational modifications (PTMs). Further, we evaluated potential biomarkers in the bile fluid for diagnosis of eCCA and differentiation between eCCA and benign biliary disease. Methods From August 2018 to April 2019, we obtained bile fluids from 46 patients; 28 patients with eCCA (eCCA group) and 18 patients with common bile duct stone (Control group) via percutaneous transhepatic biliary drainage. We examined the levels of reduced glutathione (GSH), peroxide, ferrous iron [Fe+2], glutathione peroxidase (GPX) and farnesyl transferase/geranylgeranyl transferase type-1 subunit alpha (FNTA) concentration in bile fluids to clarify the mechanism of ferroptosis and prenylation. Results The remarkable difference of PTMs was that FNTA which means prenylated cysteine as regulator was significantly decreased in eCCA than that of control. In addition, level of GSH, peroxide, GPX and ferrous iron [Fe+2] were significantly depleted in eCCA than control. These results demonstrate that PTM, dysregulated iron metabolism and GPX-regulated ferroptosis with GSH depletion through cysteine modification in bile are possible mechanisms of eCCA. Liquid Chromatography (LC)-Mass Spectrometry (MS) analysis, several oncogenic pathways including MYC target, apoptosis, fatty acid metabolism, P53 and mTORC1 were enriched in eCCA. Conclusions In conclusion, redox-dependent modification of cysteine and ferroptosis in bile fluids are possible mechanisms of eCCA. Several protein and oncogenic pathways related to PTM which are seen in eCCA tissues were also enriched in bile fluids. It suggests that bile fluid represents the oncogenic characteristics of eCCA tissues. Therefore, bile fluids have a role of a biomarker for diagnosis in eCCA, especially, differentiation of eCCA from benign biliary stricture.

Lung cancer is the most common cause of cancer death in the world. However, recent studies have found that patients with pulmonary ground-glass opacity (GGO) have a better prognosis. Considering its low invasiveness, sublobar resection may be an appropriate treatment of choice. Low-dose computed tomography (CT) is recommended for the high-risk groups of lung cancer. Patients with nonsolid nodule are suggested to take annual low dose CT following-up. For part-solid or solid nodules, the solid component size less or more than 8 mm is the watershed of surgical treatment. Increasing tumor size is a hint of malignancy. Biopsy can be performed for clinically highly suspected malignant nodules. The endobronchial ultrasound biopsy, CT-guide biopsy, or surgical excision are the mainstream for the diagnosis of lung nodules. But for treatment, the sublobar resection is the mainstream of pulmonary GGO. A precise localization technique makes surgeons get enough resection margin and preserve more pulmonary function of the patients. The different localization technique is suitable for different kind nodular position. For patients with pure pulmonary GGO, annual low dose CT checkup is suitable. If the tumor size or solid part of the tumors increased gradually, adequate sublobar resection after tumor localization technique may provide good prognosis and preserve more pulmonary function of the patients.

Highlights • T-cell responses in term of frequency and intensity are clearly distinct between mild illness and severe pneumonia patients. • High levels of IFNᵧ production observed with all CoV proteins support that SARS-CoV-2 elicit potent memory immune responses. • Recent history of COVID-19 did not hamper viral memory T-cell pool against common viruses., Adaptive Immune responses generated by SARS-CoV-2 virus in convalescent patients according to disease severity remain poorly characterized. To this end, we designed a prospective study (NCT04365322) that included 60 COVID-19 convalescent patients (1-month post infection) in two cohorts respectively entitled mild illness and severe pneumonia. The monitoring of peripheral immune responses was performed using IFNᵧ ELISpot assay. The serology index of each patient was investigated at the same time. Patients with severe pneumonia were older and had more comorbidities than patients with mild illness. T-cell responses in term of frequency and intensity were clearly distinct between mild illness and severe pneumonia patients. Furthermore, our results demonstrated that recent history of COVID-19 did not hamper viral memory T-cell pool against common viruses (Cytomegalovirus, Epstein-Barr-virus and Flu-virus). The presence of potent adaptive immunity even in patients who underwent severe pneumonia sustain the rationale for the development of protective therapeutics against SARS-CoV-2.