Explore the vast range of titles available.

The proliferation of new psychoactive substances (NPS) poses a significant challenge to clinical and forensic toxicology laboratories. N,N-dimethylpentylone, a novel synthetic cathinone, has emerged as a public health concern. The aims of this study are to describe the clinical presentation of N,N-dimethylpentylone poisoning, to describe detection methods, and to deduce its metabolic pathways. Clinical data was collected and reviewed retrospectively from patients with confirmed N,N-dimethylpentylone exposure. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to identify N,N-dimethylpentylone and its metabolites in urine samples. The metabolic pathway was characterised by comparison of the detected substances with reference standards. Eight cases were included in the case series. Seven different metabolites of N,N-dimethylpentylone were identified in in vivo patient urine samples, where the two major metabolic pathways were proposed to be opening of the 5-membered ring and reduction of carboxide. All patients presented with neuropsychiatric and/or cardiovascular symptoms. Co-ingestion with other substances was reported in all cases. One patient requiring intensive care was described in detail. All patients eventually recovered. The analytical method allowed the simultaneous identification of N,N-dimethylpentylone, pentylone and bisdesmethyl-N,N-dimethylpentylone, as well as other drugs of abuse in patient samples. N,N-dimethylpentylone appears to be less potent than its metabolite pentylone. Co-ingestion with other drugs of abuse is common. Poisoning cases have neuropsychiatric and cardiovascular manifestations. An updated and comprehensive laboratory method is needed for its detection. •N,N-dimethylpentylone is a novel synthetic cathinone of public health concern.•Metabolites of N,N-dimethylpentylone were identified in patient urine samples.•Co-ingestion of N,N-dimethylpentylone with other substances of abuse was common.•All cases presented with neuropsychiatric and/or cardiovascular symptoms.•An updated and comprehensive laboratory method is needed for its detection.

We investigated if programmed death-ligand 1 (PD-L1) expression levels were prognostic of survival outcomes after intensity-modulated radiation therapy (IMRT) for non-metastatic nasopharyngeal carcinoma (NPC). 104 patients with non-metastatic NPC treated with radical IMRT were investigated for their PD-L1 expression by immunohistochemistry (IHC) which were correlated with survival endpoints including locoregional failure-free survival (LRFFS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and overall survival (OS). After a median follow-up of 7.6 years, 21 (20.2%), 19 (18.3%) and 31 (29.8%) patients suffered from locoregional failure, distant metastases and overall disease progression, respectively, and 31 (29.8%) patients died. Patients whose tumors had PD-L1 IHC 2+ (moderate to strong membrane staining in ≥ 25% of tumor cells) enjoyed longer LRFFS (5-year 100% vs. 74.4%, Hazard ratio [HR], 0.159, 95% confidence interval [CI], 0.021-0.988; P = 0.042) and marginally longer PFS (5-year 95.0% vs. 65.2%, HR, 0.351, 95% CI, 0.08-0.999, P = 0.067) compared to those whose tumors had PD-L1 IHC 0 (minimal membrane staining with PD-L1 in < 5% tumor cells or no staining with PD-L1) or 1+ (minimal to moderate membrane staining with PD-L1 in between 5-24% tumor cells). PD-L1 IHC 2+ was independently prognostic of both LRFFS (P = 0.014) and PFS (P = 0.045) in multivariable analyses. Only induction chemotherapy followed by concurrent chemoradiation was prognostic of DMFS (P = 0.003) and no prognostic factor for OS was identified. PD-L1 expression levels correlated with LRRFS and PFS in non-metastatic NPC treated with radical IMRT. It may play a role in radiosensitivity for NPC, which should be further confirmed in prospective studies using immunotherapy together with IMRT.

Stem cells need to be protected from genotoxic and proteotoxic stress to maintain a healthy pool throughout life1–3. Little is known about the proteostasis mechanism that safeguards stem cells. Here we report endoplasmic reticulum-associated degradation (ERAD) as a protein quality checkpoint that controls the haematopoietic stem cell (HSC)–niche interaction and determines the fate of HSCs. The SEL1L–HRD1 complex, the most conserved branch of ERAD4, is highly expressed in HSCs. Deletion of Sel1l led to niche displacement of HSCs and a complete loss of HSC identity, and allowed highly efficient donor-HSC engraftment without irradiation. Mechanistic studies identified MPL, the master regulator of HSC identity5, as a bona fide ERAD substrate that became aggregated in the endoplasmic reticulum following ERAD deficiency. Restoration of MPL signalling with an agonist partially rescued the number and reconstitution capacity of Sel1l-deficient HSCs. Our study defines ERAD as an essential proteostasis mechanism to safeguard a healthy stem cell pool by regulating the stem cell–niche interaction.Xu, Liu, Pen, Zhang et al. demonstrate that the SEL1L–HRD1 complex, which is part of the ERAD protein quality control machinery, safeguards haematopoietic stem cell identity and niche location by ensuring the haematopoietic stem cell surface expression of MPL.

The presence of heterogeneity in responses to oncolytic virotherapy poses a barrier to clinical effectiveness, as resistance to this treatment can occur through the inhibition of viral spread within the tumor, potentially leading to treatment failures. Here we show that 4-octyl itaconate (4-OI), a chemical derivative of the Krebs cycle-derived metabolite itaconate, enhances oncolytic virotherapy with VSVΔ51 in various models including human and murine resistant cancer cell lines, three-dimensional (3D) patient-derived colon tumoroids and organotypic brain tumor slices. Furthermore, 4-OI in combination with VSVΔ51 improves therapeutic outcomes in a resistant murine colon tumor model. Mechanistically, we find that 4-OI suppresses antiviral immunity in cancer cells through the modification of cysteine residues in MAVS and IKKβ independently of the NRF2/KEAP1 axis. We propose that the combination of a metabolite-derived drug with an oncolytic virus agent can greatly improve anticancer therapeutic outcomes by direct interference with the type I IFN and NF-κB-mediated antiviral responses. The use of oncolytic viruses as a therapy for cancer is limited by mechanisms inhibiting viral replication in the tumor. Here, the authors show that a chemical derivative of itaconate, 4-octyl itaconate, increases oncolytic virus VSVΔ51 efficacy in various cancer models, through decreasing antiviral immunity.

IntroductionBreast cancer is the leading cause of global cancer incidence and represents 11.7% of all new cancer cases. However, breast cancer survivors (BCS) suffer from many intense physical and psychological symptoms, functional deficits and adverse effects during and after treatment, significantly affecting their quality of life. Virtual reality (VR) technology uses computer technology to create an interactive three-dimensional world by visual, audio and touch simulation and is being used in breast cancer rehabilitation management. This paper reports on the protocol for a systematic review and meta-analysis exploring the efficacy of VR-based interventions in the rehabilitation management of BCS.Methods and analysisThis protocol for conducting a systematic review and meta-analysis was prepared according to the recommendations of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 statement. Web of Science, PubMed, Embase, CINAHL, Cochrane Central Register of Controlled Trials, CNKI, Wanfang, VIP and SinoMed will be used in the search. The search will include randomised controlled trials, quasi-experimental studies and case-controlled trials published in English and Chinese. Further, the risk of bias of the studies included in the systematic review and meta-analysis will be assessed using the Cochrane risk-of-bias tool. The statistical program Review Manager V.5.3 will be used in the meta-analysis. The I² test will be used to determine statistical heterogeneity among the included studies.Ethics and disseminationEthics approval will not be needed because the data to be used in this systematic review and meta-analysis will be extracted from published studies. The systematic review and meta-analysis will focus on whether VR-based interventions are effective in the rehabilitation management of BCS. It will be disseminated by publication in a peer-reviewed journal.PROSPERO registration numberCRD42021250727.

Stroke has the highest disability-adjusted life-years lost in any disease, and approximately one-third of the patients get aphasia. Computers and tablets are innovative and aid in intensive treatments in speech rehabilitation for patients with aphasia. However, mechanical training limits the help to patients. This study aims to provide a framework for an integrated virtual reality (VR) app to provide speech rehabilitation for patients with aphasia. The content was generated through an in-depth literature review and discussion with experienced rehabilitation physicians and occupational therapists. We then conducted a 2-round Delphi study with 15 experts from hospitals and universities to rate the content using a 5-point Likert scale. The app was developed by an interdisciplinary team involving VR, medical science of rehabilitation, and therapeutic rehabilitation. Pilot usability testing of this novel app was conducted among 5 patients with aphasia, 5 healthy volunteers, 5 medical staff, and 2 VR experts. We designed 4 modules of speech rehabilitation: oral expression, auditory comprehension, cognition, and comprehensive application. Our VR-based interactive and intelligent app was developed to provide an alternative option for patients with aphasia. Pilot usability testing revealed user satisfaction with the app. This study designed and tested a novel VR-based app for speech rehabilitation specifically adapted to patients with aphasia. This will guide other studies to develop a similar program or intelligent system in a clinical setting.

Nasopharyngeal carcinoma (NPC) is endemic to Eastern and South-Eastern Asia, and, in 2020, 77% of global cases were diagnosed in these regions. Apart from its distinct epidemiology, the natural behavior, treatment, and prognosis are different from other head and neck cancers. With the growing trend of artificial intelligence (AI), especially deep learning (DL), in head and neck cancer care, we sought to explore the unique clinical application and implementation direction of AI in the management of NPC. The search protocol was performed to collect publications using AI, machine learning (ML) and DL in NPC management from PubMed, Scopus and Embase. The articles were filtered using inclusion and exclusion criteria, and the quality of the papers was assessed. Data were extracted from the finalized articles. A total of 78 articles were reviewed after removing duplicates and papers that did not meet the inclusion and exclusion criteria. After quality assessment, 60 papers were included in the current study. There were four main types of applications, which were auto-contouring, diagnosis, prognosis, and miscellaneous applications (especially on radiotherapy planning). The different forms of convolutional neural networks (CNNs) accounted for the majority of DL algorithms used, while the artificial neural network (ANN) was the most frequent ML model implemented. There is an overall positive impact identified from AI implementation in the management of NPC. With improving AI algorithms, we envisage AI will be available as a routine application in a clinical setting soon.

Introduction: Nasopharyngeal carcinoma (NPC) is endemic to Eastern and South-Eastern Asia, and, in 2020, 77% of global cases were diagnosed in these regions. Apart from its distinct epidemiology, the natural behavior, treatment, and prognosis are different from other head and neck cancers. With the growing trend of artificial intelligence (AI), especially deep learning (DL), in head and neck cancer care, we sought to explore the unique clinical application and implementation direction of AI in the management of NPC. Methods: The search protocol was performed to collect publications using AI, machine learning (ML) and DL in NPC management from PubMed, Scopus and Embase. The articles were filtered using inclusion and exclusion criteria, and the quality of the papers was assessed. Data were extracted from the finalized articles. Results: A total of 78 articles were reviewed after removing duplicates and papers that did not meet the inclusion and exclusion criteria. After quality assessment, 60 papers were included in the current study. There were four main types of applications, which were auto-contouring, diagnosis, prognosis, and miscellaneous applications (especially on radiotherapy planning). The different forms of convolutional neural networks (CNNs) accounted for the majority of DL algorithms used, while the artificial neural network (ANN) was the most frequent ML model implemented. Conclusion: There is an overall positive impact identified from AI implementation in the management of NPC. With improving AI algorithms, we envisage AI will be available as a routine application in a clinical setting soon. Keywords: machine learning, neural network, deep learning, prognosis, diagnosis, auto contouring

Additional risk factors include hypotension, multiple renal arteries, and unidentified intimal flaps, young age of the recipient, young age of the deceased donor, prolonged cold ischaemic time, history of transplantation, and presence of acute tubular necrosis. [4] In cases where ultrasonographic identification of the main renal artery is challenging due to technical factors such as postoperative gas limiting the acoustic window or a lack of operator experience, magnetic resonance (MR) or contrast computed tomography (CT) angiogram can provide a definitive diagnosis. Ultrasound scan on day 10 showed no blood flow in the graft kidney on (a) colourand (b) power Doppler studies. (c, d) Contrast-enhanced computed tomography showed no contrast enhancement in the graft kidney whilesatisfactory contrast opacification of the inferior vena cava and aorta and bilateral iliac vessels were both seen (solid arrows). Creatinine was persistently elevated.Ultrasound showed markedly reduced graft kidney perfusion.Renal vein colour flow was absent. (a) A thrombosed renal veinwas seen as a hypoechoic tubular structure in the renal hilum.(b, c) Contrast computed tomography showed a hyperdensenon-enhancing, distended renal vein (white arrows) compatiblewith renal vein thrombosis.

Atherosclerosis imaging with 18F-FDG PET is useful for tracking inflammation within plaque and monitoring the response to drug therapy. Short-term reproducibility of this technique in peripheral artery disease has not been assessed, and the optimal method of 18F-FDG quantification is still debated. We imaged 20 patients with vascular disease using 18F-FDG PET twice, 14 d apart, and used these data to assess reproducibility measures and compare 2 methods of 18F-FDG uptake measurement. We also reviewed the literature on quantification methods to determine the optimal measures of arterial 18F-FDG uptake for future studies. Twenty patients with vascular disease underwent PET/CT of the iliac, femoral, and carotid arteries 90 min after 18F-FDG administration. In 19 patients, repeat testing was performed at 2 wk. Coregistration and attenuation correction were performed with CT. Vessel 18F-FDG uptake was measured as both the mean and maximum blood-normalized standardized uptake value (SUV), known as the target-to-background ratio (TBR). We assessed interscan, interobserver, and intraobserver agreement. Nineteen patients completed both imaging sessions. The carotid and peripheral arteries all have excellent short-term reproducibility of the 18F-FDG signal, with intraclass correlation coefficients all greater than 0.8 for all measures of reproducibility. Both mean and maximum TBR measurements for quantifying 18F-FDG uptake are equally reproducible. 18F-FDG uptake was significantly higher in the carotid arteries than in both iliac and femoral vessels (P < 0.001 for both). We found that both mean and maximum TBR in the carotid, iliac, and femoral arteries were highly reproducible. We suggest the mean TBR be used for tracking systemic arterial therapies, whereas the maximum TBR is optimal for detecting and monitoring local, plaque-based therapy.