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Background and AimsHistone deacetylase inhibitors [HDACi] exert potent anti-inflammatory effects. Because of the ubiquitous expression of HDACs, clinical utility of HDACi is limited by off-target effects. Esterase-sensitive motif [ESM] technology aims to deliver ESM-conjugated compounds to human mononuclear myeloid cells, based on their expression of carboxylesterase 1 [CES1]. This study aims to investigate utility of an ESM-tagged HDACi in inflammatory bowel disease [IBD].MethodsCES1 expression was assessed in human blood, in vitro differentiated macrophage and dendritic cells, and Crohn’s disease [CD] colon mucosa, by mass cytometry, quantitative polymerase chain reaction [PCR], and immunofluorescence staining, respectively. ESM-HDAC528 intracellular retention was evaluated by mass spectrometry. Clinical efficacy of ESM-HDAC528 was tested in dextran sulphate sodium [DSS]-induced colitis and T cell transfer colitis models using transgenic mice expressing human CES1 under the CD68 promoter.ResultsCES1 mRNA was highly expressed in human blood CD14+ monocytes, in vitro differentiated and lipopolysaccharide [LPS]-stimulated macrophages, and dendritic cells. Specific hydrolysis and intracellular retention of ESM-HDAC528 in CES1+ cells was demonstrated. ESM-HDAC528 inhibited LPS-stimulated IL-6 and TNF-α production 1000 times more potently than its control, HDAC800, in CES1high monocytes. In healthy donor peripheral blood, CES1 expression was significantly higher in CD14++CD16- monocytes compared with CD14+CD16++ monocytes. In CD-inflamed colon, a higher number of mucosal CD68+ macrophages expressed CES1 compared with non-inflamed mucosa. In vivo, ESM-HDAC528 reduced monocyte differentiation in the colon and significantly improved colitis in a T cell transfer model, while having limited potential in ameliorating DSS-induced colitis.ConclusionsWe demonstrate that monocytes and inflammatory macrophages specifically express CES1, and can be preferentially targeted by ESM-HDAC528 to achieve therapeutic benefit in IBD.

Tinea capitis is still common in developing countries, such as China. Its pathogen spectrum varies across regions and changes over time.This study aimed to clarify the current epidemiological characteristics and pathogen spectrum of tinea capitis in China.A multicentre, prospective descriptive study involving 29 tertiary hospitals in China was conducted. From August 2019 to July 2020, 611 patients with tinea capitis were enrolled. Data concerning demography, risk factors and fungal tests were collected. When necessary, the pathogens were further identified by morphology or molecular sequencing in the central laboratory.Among all enrolled patients, 74·1% of the cases were in patients aged 2-8 years. The children with tinea capitis were mainly boys (56·2%) and were more likely than adults to have a history of animal contact (57·4% vs. 35·3%, P = 0·012) and zoophilic dermatophyte infection (73·5% vs. 47%). The adults were mainly female (83%) and were more likely than children to have anthropophilic agent infection (53% vs. 23·9%). The most common pathogen was zoophilic Microsporum canis (354, 65·2%), followed by anthropophilic Trichophyton violaceum (74, 13·6%). In contrast to the eastern, western and northeastern regions, where zoophilic M. canis predominated, anthropophilic T. violaceum predominated in central China (69%, P 0·001), where the patients had the most tinea at other sites (20%) and dermatophytosis contact (26%) but the least animal contact (39%). Microsporum ferrugineum was the most common anthropophilic agent in the western area, especially in Xinjiang province.Boys aged approximately 5 years were the most commonly affected group. Dermatologists are advised to pay more attention to the different transmission routes and pathogen spectra in different age groups from different regions.

Single wall carbon nanotubes (SWCNTs) have long been proposed as a candidate to enhance existing photovoltaic materials by providing an extension to the light absorbed in the infrared. In this work, we discuss the validity of this statement for silicon solar cells and couple a bifacial silicon solar cell to an organic SWCNT cell in a 4-terminal stack. Single chiral species of (6,5), (7,6), and (10,3) are used in the organic cell and the overall contribution to photocurrent from the SWCNTs is discussed in terms of the diameter dependent quantum efficiency, film thickness, the transmittance of silicon, the spectral overlap of the SWCNT's absorbance with the solar irradiance spectrum and the maximum obtainable current density in the infrared.

Objective: Synovial inflammation contributes to cartilage degeneration and osteoarthritis (OA) development. Targeting the inflammation process may provide a promising strategy for OA treatment. It has been demonstrated that C1q/tumour necrosis factor-related protein-9 (CTRP9) has immunosuppression capabilities. Thus, we conducted this study to investigate the role of CTRP9 in OA and its therapeutic potential.Method: The expression level of CTRP9 was quantified in peripheral blood mononuclear cells (PBMCs), serum, and synovial cells (SCs) isolated from OA patients by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. The relationship between the expression level of CTRP9 and the disease activity of OA was determined. The inflammation-suppressing effects of CTRP9 were assessed in vitro.Results: The expression level of CTRP9 was increased in the PBMCs and serum of OA compared to healthy controls. The serum level of CTRP9 was found to be positively correlated with erythrocyte sedimentation rate, C-reactive protein, and visual analogue scale score. In addition, CTRP9 protein suppressed the expression of pro-inflammatory cytokines, including tumour necrosis factor-α, interleukin-6, and interleukin-1β, in PBMCs and SCs in vitro. CTRP9 was increased in OA patients and positively correlated with the disease activity. The recombinant CTRP9 had inflammation-suppressing activities in vitro.Conclusion: CTRP9 may have therapeutic potential for treating OA.Osteoarthritis (OA) is characterized as cartilage destruction resulting from synovial inflammation (1-6). According to the clinical symptoms and levels of inflammation, OA has been divided into primary generalized osteoarthritis (PGOA) and erosive inflammatory osteoarthritis (EIOA) (7). The only available treatment for OA is joint replacement. Thus, it is necessary to develop novel and effective therapeutic strategies to treat OA.Because synovial inflammation contributes to OA development, targeting the inflammation process may provide a promising strategy for OA treatment. Previous investigations showed that pro-inflammatory factors promoted OA development (8-10), while anti-inflammatory factors suppressed it (11-14). Thus, we conducted the present study to investigate the role of C1q/tumour necrosis factor-related protein-9 (CTRP9), an anti-inflammatory factor (15), in OA, and its therapeutic potential.

An overview of the clinical observation of a patient with the consequences of severe traumatic brain injury, with a tracheoesophageal fistula is presented. The article discusses a staged multidisciplinary approach to treatment.

With the development of technology and geospatial equipment, more and more work, particularly covering a big area survey and mapping work, are conducted with different worker and equipment, or heterogeneous time variation. With the traditional data quality focus on the geospatial data quality itself, which is not include the work files and organization. Facing the heterogeneous characteristics of geospatial data and work organization, a full life data quality workflow was proposed to manage and control geospatial data quality. The proposed workflow is extended to include the file preparation, quality evaluation, and quality calculation phrases. It is demonstrated in one real data quality project, which include vector data, raster data and other geospatial data covering 160 thousands square kilometers and 300 work zones finished by 8 teams. The usability and reliability were validated in our work.

Though the thenar flap has been described since 1926, its use has not been widespread. The main criticisms are donor site morbidity and proximal interphalangeal joint (PIPJ) stiffness. In this paper, we describe a standard design technique for flap design and division to address these two issues. From July 2018 to April 2019, a total of ten patients underwent thenar flap reconstruction of the fingertip. The flap dimensions ranged from 10 mm × 10 mm to 25 mm × 15 mm. All the flaps survived. One patient developed wound infection post division. All donor sites were closed primarily without skin graft. We are using mirror image technique to elevate the flap to ensure that it is inset in the position as we planned without displacement. It largely reduced the chance of rotation and extensive tension when fix the finger to the thenar region. Our technique allows for the flap design to be individually customized based on the orientation of the defect, making it simpler and more replicable. We have also emphasized how care during division of the thenar flap can help prevent complications.

Objective:To assess the potential for contamination of personnel, patients, and the environment during use of contaminated N95 respirators and to compare the effectiveness of interventions to reduce contamination.Design:Simulation study of patient care interactions using N95 respirators contaminated with a higher and lower inocula of the benign virus bacteriophage MS2.Methods:In total, 12 healthcare personnel performed 3 standardized examinations of mannequins including (1) control with suboptimal respirator handling technique, (2) improved technique with glove change after each N95 contact, and (3) control with 1-minute ultraviolet-C light (UV-C) treatment prior to donning. The order of the examinations was randomized within each subject. The frequencies of contamination were compared among groups. Observations and simulations with fluorescent lotion were used to assess routes of transfer leading to contamination.Results:With suboptimal respirator handling technique, bacteriophage MS2 was frequently transferred to the participants, mannequin, and environmental surfaces and fomites. Improved technique resulted in significantly reduced transfer of MS2 in the higher inoculum simulations (P < .01), whereas UV-C treatment reduced transfer in both the higher- and lower-inoculum simulations (P < .01). Observations and simulations with fluorescent lotion demonstrated multiple potential routes of transfer to participants, mannequin, and surfaces, including both direct contact with the contaminated respirator and indirect contact via contaminated gloves.Conclusion:Reuse of contaminated N95 respirators can result in contamination of personnel and the environment even when correct technique is used. Decontamination technologies, such as UV-C, could reduce the risk for transmission.

The objective of the work is to evaluate the feasibility of improving selective stimulation and reducing muscle fatigue in upper extremity rehabilitation with a self-designed multi-site functional electrical stimulation (FES) prototype. The design of the prototype is a distributed architecture concept, and all the modules communicate within a single local area network controlled by the Android application (APP). To improve the efficiency of the prototype, the APP was developed to utilize a simple online algorithm to perform a rapid real-time search for the optimal stimulation site. One healthy subject participated in a multi-site FES trial consisting of a search for the optimal stimulating electrode test and a fatigue stimulation test. Comparing the results of the online automatic search for the optimal stimulation site test with the results of the offline analysis, the average Location Error for the extension and flexion motions were 1.5 cm and 2.8 cm, respectively. For the fatigue stimulation test, all the assessments of the multi-site sequential stimulation group were higher than those of the conventional stimulation, with a significant 193% higher Fatigue Index (P=0.003) and 300% longer Fatigue Time (P=0.005). These results suggest that multi-site FES may exert positive effects on selective stimulation and stimulation fatigue reduction in healthy subjects.

Background Previous studies have found that patients with subclinical interstitial lung disease (ILD) are highly susceptible to developing radiation pneumonitis (RP) after thoracic radiation therapy. In the present study we aimed to evaluate the incidence of and risk factors for RP after thoracic intensity-modulated radiation therapy in lung cancer patients with subclinical ILD. Methods We retrospectively analyzed data from lung cancer patients with subclinical ILD who were treated with thoracic intensity-modulated radiation therapy with a prescribed dose of ≥ 50 Gy in our institution between January 2016 and December 2017. Results Eighty-seven consecutive lung cancer patients with subclinical ILD were selected for the study. The median follow-up period was 14.0 months. The cumulative incidence of grades ≥ 2 and ≥ 3 RP at one year was 51.0% and 20.9%, respectively. In the multivariate analysis, a mean lung dose ≥ 12 Gy was a significant risk factor for grade ≥ 2 RP (p = 0.049). Chemotherapy with gemcitabine in the past, V5 ≥ 50%, and subclinical ILD involving ≥ 25% of the lung volume were significantly associated with grade ≥ 3 RP (p = 0.046, p = 0.040, and p = 0.024, respectively). Conclusion Mean lung dose is a significant risk factor for grade ≥ 2 RP. Lung cancer patients who have received chemotherapy with gemcitabine in the past, V5 ≥ 50%, and those with subclinical ILD involving ≥ 25% of lung volume have an increased risk of grade ≥ 3 RP in lung cancer patients with subclinical ILD.

BACKGROUND The aim of the present study was to establish a new prediction model for radiation pneumonitis (RP) in locally advanced non-small cell lung cancer (LA-NSCLC) patients before and after radiotherapy. METHODS The study involved 153 patients. Age, arterial partial oxygen pressure (PO2), forced vital capacity, pulmonary emphysema (PE), subclinical interstitial lung disease (sILD), and dosimetric parameters, such as mean lung dose and percentage of lung volume, and a dose >5/20 Gy (V5/V20), were considered candidate RP predictors. RESULTS Of the 153 eligible patients, 33 (21.6%) developed RP, 68 had PE (43.8%), and 24 (15.7%) had sILD. Grades 2, 3, and 5 RP were scored in 17 (11.1%), 15 (9.8%), and 1 (0.7%) patient/s, Grade 4 RP was not observed. Grades 1, 2, and 3 PE were scored in 45 (29.4%), 22 (14.4%), and 1 (0.7%) patient/s. Grades 0 and 1 sILD were observed in 129 (84.3%) and 24 (15.7%) patients. Univariate analysis found age, PE, and sILD to be significantly correlated with grade ≥2 RP. Multivariate analysis revealed age >68 years, PE grade >1, and sILD grade ≥1 as independent risk factor for grade ≥2 RP in LA-NSCLC with squamous cell carcinoma (SCC). Finally, a new predictive risk score (PRS) comprised of these factors was developed. The PRS score was 0, 3-5, and 6-11 when the cumulative incidence of grade ≥2 RP was 8.8% (5 patients), 13% (3 patients), and 84.6% (13 patients) (P=

The aim of the present study was to elucidate the functional role of hsa-miR-328-3p/STAT3 pathway in the effects of propofol on gastric cancer proliferation. Bioinformatics was used to analyze the molecular expression differences of hsa-miR-328-3p/STAT3 axis in stomach adenocarcinoma (n = 435) and normal samples (n = 41) from TCGA database. The expression of the above molecules in gastric cancer cells SGC-7901 and normal gastric mucosal cells GES-1 was verified via qPCR. The dual-luciferase assay was carried out to confirm the interaction between hsa-miR-328-3p and STAT3. Subsequently, the cell proliferation and the expression of the above molecules in SGC-7901 and GES-1 cells were evaluated after 10 μM propofol treatment. Finally, we analyzed whether propofol still inhibited the proliferation of gastric cancer by suppressing STAT3 pathway after hsa-miR-328-3p down-regulation. Compared with normal samples, the expression of hsa-miR-328-3p was significantly down-regulated in stomach adenocarcinoma samples, while the expression of STAT3 and downstream target genes (MMP2, CCND1 and COX2) was up-regulated. The results were consistent with those in GES-1 and SGC-7901 cell lines. Meanwhile, we found that hsa-miR-328-3p can bind to the 3′-UTR of the potential target gene STAT3. Furthermore, propofol significantly inhibited the proliferation of gastric cancer cell line SGC-7901, where hsa-miR-328-3p was up-regulated and the expression of STAT3 and downstream proliferation-related target genes were down-regulated. However, the growth inhibition of propofol on SGC-7901 cell was significantly reversed after the inhibition of hsa-miR-328-3p. To sum up, propofol suppressed the STAT3 pathway via up-regulating hsa-miR-328-3p to inhibit gastric cancer proliferation.

Hand hygiene is a critical strategy for infection prevention in all healthcare settings. Automated electronic monitoring systems are expected to improve hand hygiene performance.To investigate the impact of the Internet of Things (IoT) management system on hand hygiene compliance among medical staff in an emergency intensive care unit (EICU).This retrospective observational study was conducted between July 1After the application of the IoT management system, the hand hygiene compliance rates among the members of the medical staff before (29.5% (3347/11,338) vs 57.9% (4690/8094), P 0.001) and after (59.9% (9915/16,556) vs 73.8% (17,194/23 286), P 0.001) the contact with patients and surrounding environment significantly improved. However, hand hygiene compliance among three cleaning staff did not significantly improve after the application. Moreover, there was no significant difference in healthcare-acquired infection rates (2.535% (9/355) vs 2.047% (7/342), P = 0.667) nor in the detection rates of the four major multidrug-resistant bacteria in the EICU before and after the application of the IoT management system (P 0.05).The IoT management system significantly improved hand hygiene compliance among medical staff, except cleaners, in the EICU of one provincial hospital; however, the rates of nosocomial infection did not significantly decrease. The quality of hand hygiene implementation needs to be improved.

This article presents a novel decoupling technique for the circularly polarized multiple-inputmultiple- output (CP-MIMO) system composed of Guoshaped patch antennas. A comparative study has been conducted on antenna performance as a function of packing distance before and after applying the technique. A prototype of two-element Guo-shaped patch MIMO at a small inter-element spacing of 12.5 mm has devised aiming for the 5G new radio n38 (2.57-2.62 GHz) applications. Simulation reinforced with experimental results confirmed the effectiveness of the proposed technique, whereas the two Guo-shaped patch elements packed in such small spacing can be operated independently. Both the envelope correlation coefficient and diversity gain are approaching their ideal values.

Objective To evaluate the use of Ilizarov external mini-fixation in the treatment of Monteggia fractures (dislocation of the radial head with an associated fracture of the proximal ulna) in children. Methods Children with proximal ulnar fracture were included and underwent fracture reduction surgery with Ilizarov external mini-fixators, followed by immobilization of the supinated forearm with plaster. The reduction was evaluated intra-operatively using arthrography. Mackay criteria were used to evaluate clinical outcomes at follow-up. Results A total of 15 children were included in the study. Mackay efficacy was 100 %, indicating excellent outcomes using the Ilizarov external mini-fixator. Conclusion Use of the Ilizarov external mini–fixator is particularly suitable in the treatment of children with comminuted and compression fractures of proximal ulna. It is easy to operate, low invasive and is worthy of promotion.

Atmospheric turbulence reduces the image quality and resolution of ground-based optical telescopes. Future large solar telescopes (e.g. the CGST, China Giant Solar Telescope) should be equipped with adaptive optics (AO) systems. The design of AO systems is associated with atmospheric optical turbulence parameters, especially the profile of the refractive index structure $C_{n}^{2}(h)$. With the solar differential image motion monitor (S-DIMM) and the profiler of the moon limb (PML), a simplified version of a PML, termed a profiler of the differential solar limb (PDSL), was built in order to determine the daytime $C_{n}^{2}(h)$ and other atmospheric turbulence parameters. A PDSL with differential solar limb fluctuations was used to determine the turbulence profiling, and the extended solar limb extends the range of separation angles for a higher resolution of the height profile. The PDSL structure and its performance are described. In addition, numerical simulations were conducted to verify the effectiveness of the method. As revealed from the simulation results, the layered integral coefficient matrix is capable of solving the discretization error and enhancing the inversion accuracy of the turbulence contour. The first test results at Mt Wumingshan (a candidate site for the CGST) are presented.

Background:There is controversy regarding whether the addition of cover gowns offers a substantial benefit over gloves alone in reducing personnel contamination and preventing pathogen transmission.Design:Simulated patient care interactions.Objective:To evaluate the efficacy of different types of barrier precautions and to identify routes of transmission.Methods:In randomly ordered sequence, 30 personnel each performed 3 standardized examinations of mannequins contaminated with pathogen surrogate markers (cauliflower mosaic virus DNA, bacteriophage MS2, nontoxigenic Clostridioides difficile spores, and fluorescent tracer) while wearing no barriers, gloves, or gloves plus gowns followed by examination of a noncontaminated mannequin. We compared the frequency and routes of transfer of the surrogate markers to the second mannequin or the environment.Results:For a composite of all surrogate markers, transfer by hands occurred at significantly lower rates in the gloves-alone group (OR, 0.02; P < .001) and the gloves-plus-gown group (OR, 0.06; P = .002). Transfer by stethoscope diaphragms was common in all groups and was reduced by wiping the stethoscope between simulations (OR, 0.06; P < .001). Compared to the no-barriers group, wearing a cover gown and gloves resulted in reduced contamination of clothing (OR, 0.15; P < .001), but wearing gloves alone did not.Conclusions:Wearing gloves alone or gloves plus gowns reduces hand transfer of pathogens but may not address transfer by devices such as stethoscopes. Cover gowns reduce the risk of contaminating the clothing of personnel.

Background:Critical shortages of personal protective equipment, especially N95 respirators, during the coronavirus disease 2019 (COVID-19) pandemic continues to be a source of concern. Novel methods of N95 filtering face-piece respirator decontamination that can be scaled-up for in-hospital use can help address this concern and keep healthcare workers (HCWs) safe.Methods:A multidisciplinary pragmatic study was conducted to evaluate the use of an ultrasonic room high-level disinfection system (HLDS) that generates aerosolized peracetic acid (PAA) and hydrogen peroxide for decontamination of large numbers of N95 respirators. A cycle duration that consistently achieved disinfection of N95 respirators (defined as ≥6 log10 reductions in bacteriophage MS2 and Geobacillus stearothermophilus spores inoculated onto respirators) was identified. The treated masks were assessed for changes to their hydrophobicity, material structure, strap elasticity, and filtration efficiency. PAA and hydrogen peroxide off-gassing from treated masks were also assessed.Results:The PAA room HLDS was effective for disinfection of bacteriophage MS2 and G. stearothermophilus spores on respirators in a 2,447 cubic-foot (69.6 cubic-meter) room with an aerosol deployment time of 16 minutes and a dwell time of 32 minutes. The total cycle time was 1 hour and 16 minutes. After 5 treatment cycles, no adverse effects were detected on filtration efficiency, structural integrity, or strap elasticity. There was no detectable off-gassing of PAA and hydrogen peroxide from the treated masks at 20 and 60 minutes after the disinfection cycle, respectively.Conclusion:The PAA room disinfection system provides a rapidly scalable solution for in-hospital decontamination of large numbers of N95 respirators during the COVID-19 pandemic.

Objective To estimate a stillbirth rate at 24 or more gestational weeks in 2015–2016 and to explore potentially preventable causes in China. Design A multi‐centre cross‐sectional study. Setting Ninety‐six hospitals distributed in 24 (of 34) provinces in China. Population A total of 75 132 births at 24 completed weeks of gestation or more. Methods COX Proportional Hazard Models were performed to examine risk factors for antepartum and intrapartum stillbirths. Population attributable risk percentage was calculated for major risk factors. Correspondence analysis was used to explore region‐specific risk factors for stillbirths. Main outcome measures Stillbirth rate and risk factors for stillbirth. Results A total of 75 132 births including 949 stillbirths were used for the final analysis, giving a weighted stillbirth rate of 13.2 per 1000 births (95% CI 7.9–18.5). Small for gestational age (SGA) and pre‐eclampsia/eclampsia increased antepartum stillbirths by 26.2% and 11.7%, respectively. Fetal anomalies increased antepartum and intrapartum stillbirths by 17.9% and 7.4%, respectively. Overall, 31.4% of all stillbirths were potentially preventable. Advanced maternal age, pre‐pregnant obesity, chronic hypertension and diabetes mellitus were important risk factors in East China; low education and SGA were major risk factors in Northwest, Southwest, Northeast and South China; and pre‐eclampsia/eclampsia and intrapartum complications were significant risk factors in Central China. Conclusions The prevalence of stillbirth was 13.2 per 1000 births in China in 2015–2016. Nearly one‐third of all stillbirths may be preventable. Strategies based on regional characteristics should be considered to reduce further the burden of stillbirths in China. Tweetable abstract The stillbirth rate was 13.2 per 1000 births in China in 2015–2016 and nearly one‐third of all stillbirths may be preventable., Tweetable abstract The stillbirth rate was 13.2 per 1000 births in China in 2015–2016 and nearly one‐third of all stillbirths may be preventable.

A Rural Rehabilitation Service Station – an experimental model catered for elderlies and mildly disabled people is being established in a village near Xian, Shanxi Province.

This paper proposes a novel design of single branch wideband rectifier working at low input power level. Both the impedance tuning part and a dual-band matching network are adopted for wideband impedance matching. Theoretical analysis of the proposed wideband rectifier is presented and its closed-form design equations are derived. As an illustrated example, a wideband rectifier is designed and fabricated. Experimental results show that the fabricated rectifier features wide operated fractional bandwidth of more than 50%, low input power level from -5.0 dBm to 5 dBm, as well as a simple circuit structure and design procedure.

Aims Nakajo-Nishimura syndrome (NNS) is an autosomal recessive disease caused by biallelic mutations in the PSMB8 gene that encodes the immunoproteasome subunit β5i. There have been only a limited number of reports on the clinicopathological features of the disease in genetically confirmed cases. Methods We studied clinical and pathological features of three NNS patients who all carry the homozygous p.G201V mutations in PSMB8. Patients' muscle specimens were analysed with histology and immunohistochemistry. Results All patients had episodes of typical periodic fever and skin rash, and later developed progressive muscle weakness and atrophy, similar to previous reports. Oral corticosteroid was used for treatment but showed no obvious efficacy. On muscle pathology, lymphocytes were present in the endomysium surrounding non-necrotic fibres, as well as in the perimysium perivascular area. Nearly all fibres strongly expressed MHC-I in the sarcolemma. In the eldest patient, there were abnormal protein aggregates in the sarcoplasm, immunoreactive to p62, TDP-43 and ubiquitin antibodies. Conclusions These results suggest that inflammation, inclusion pathology and aggregation of abnormal proteins underlie the progressive clinical course of the NNS pathomechanism.

Recent increases in deaths in the United States from synthetic opioids such as fentanyl and fentanyl analogues (fentanyls) have raised concerns about possible occupational exposures to these potent agents. Medicolegal death investigators and autopsy suite staff might perform job tasks involving exposure to fentanyls. The potential for exposure to fentanyls among medicolegal death investigators and autopsy technicians at a state medical examiner's office was evaluated through review of caseload characteristics, injury and illness logs, and procedures and policies and discussions with management and employee representatives. The evaluation showed that this medical examiner's office had low potential for work-related exposure to fentanyls; its standard operating procedures and personal protective equipment requirements should reduce the potential for occupational exposure. Medicolegal death investigation agencies can develop and implement guidance to control exposures and provide workforce education and training to reduce the potential for work-related exposure to fentanyls.

Sparse representation-based methods, as an important branch of anomaly detection (AD) technologies for hyperspectral imagery (HSI), have attracted extensive attention. How to construct an overcomplete background dictionary containing all background categories and excluding anomaly signatures is the focus. Traditional background dictionary construction methods first convert HSI into a two-dimensional matrix composed of independent spectral vectors, and then execute the subsequent construction operations. In this way, only spectral anomalies can be excluded from the background dictionary, whereas spatial anomalies still exist. To alleviate this problem, this paper proposes a novel AD algorithm through sparse representation with tensor decomposition-based dictionary construction and adaptive weighting. It has three main advantages. First, tensor representation allows the spectral and spatial characteristics of HSI to be preserved simultaneously, and Tucker decomposition achieves excellent separation between the background part and anomaly part by distinguishing them along three modes. Second, the $K$ -means++ clustering operation is implemented on the background part so that the background dictionary used for sparse representation contains all background categories. Finally, an adaptive weighting matrix derived from the anomaly part further improves the distinction between background pixels and anomalies. Experiments on synthetic and real HSI datasets demonstrate the superiority of our proposed algorithm.

The charge trapping effect of HfO2 gate stacks under heavy ion irradiation was evaluated via capacitance-voltage (C-V) measurement and transmission electron microscopy (TEM). Ion irradiation introduced oxygen vacancies into the HfO2 dielectric layer, which located primarily at the interface between HfO2 and Si. The oxygen vacancies act as trapping centers dominating the degradation of device performance after irradiation. The role of the traps on charge trapping in HfO2 gate stacks and the trapped charge stability (i.e. detrapping process) as a function of time were also investigated in this work. The mechanism of how MOS capacitors are affected by irradiation provides a good foundation for future space application of HfO2 gate stacks based integrated circuits.

Purpose Halcyon linear accelerators employ intensity‐modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT) techniques. The Halcyon offers translational, but not rotational, couch correction, which only allows a 3 degrees of freedom (3‐DOF) correction. In contrast, the TrueBeam (TB) linear accelerator offers full 6‐DOF corrections. This study aims to evaluate the difference in treatment plan quality for single thoracic or lumbar vertebral segment SBRT between the Halcyon and TB linear accelerators. In addition, this study will also investigate the effect of patient rotational setup errors on the final plan quality. Methods We analyzed 20 patients with a single‐level spine metastasis located between the T7 and L5 vertebrae near the spinal canal. The median planning target volume was 52.0 cm3 (17.9–138.7 cm3). The median tumor diameter in the axial plane was 4.6 cm (range 1.7–6.8 cm), in the sagittal plane was 3.3 cm (range 2–5 cm). The prescription doses were either 12–16 Gy in 1 fraction or 18–24 Gy in 3 fractions. All patients were treated on the TB linear accelerator with a 2.5 mm Multi‐Leaf Collimator (MLC) leaf width. Treatment plans were retrospectively created for the Halcyon, which has a 5 mm effective MLC leaf width. The 20 patients had a total of 50 treatments. Analysis of the 50 cone beam computed tomography (CBCT) scans showed average rotational setup errors of 0.6°, 1.2°, and 0.8° in pitch, yaw, and roll, respectively. Rotational error in roll was not considered in this study, as the original TB plans used a coplanar volumetric modulated arc therapy (VMAT) technique, and each 1° of roll will contribute an error of 1/360. If a plan has 3 arcs, the contribution from errors in roll will be 1° in the absence of 6‐DOF correction capabilities.

SummaryAnastomotic leakage (AL) is a frequent and potentially life-threatening postoperative complication in patients undergoing colorectal surgery with a multifactorial yet unknown pathophysiology. In the present study, we aimed to unravel AL etiology and intestinal anastomotic healing (AH) physiology focusing on both host epithelial and gut microbial components. We make use of patients-related samples and two high throughput next generation sequencing analysis approaches, including anastomotic tissue-associated bulk RNA sequencing and preoperative fecal 16S rRNA gene sequencing. We find that in the absence of host epithelial gene expression differences, the preoperative fecal microbiota of patients who undergo colorectal resection with successful AH differs in the group of patients who develop AL in the abundance of Prevotella and suggests a potential beneficial role of Prevotella that may prove useful as predictive biomarker for AH.

Background SARS-CoV-2 can spread both from symptomatic and asymptomatic individuals. Ocular manifestations due to SARS-CoV-2 have been described, being conjunctival inflammation the most common affectation. Evidence shows that conjunctivitis could be the first and/or only manifestation of COVID-19. This study aimed to develop and validate a COVID-19 screening method based on eyes photographs and artificial intelligence. Methods In this multicentre study, 1,200 participants were enrolled from Shanghai Public Health Clinical Center (SPHCC) Fudan University, AIMOMICS LAB and La Fe University and Polytechnic Hospital (LFUPH) of Valencia (Spain). Pictures of participants' ocular surface were taken in four different positions with mobile phone cameras, and a Deep Learning System (DLS) was developed through machine learning to identify characteristic conjunctival inflammation patterns. The study was conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Committees of SPHCC and LFUPH. Results The area under the receiver-operating-characteristic curve (AUC), sensitivity, specificity, and accuracy were calculated according to the results of our binary classification network. Bootstrapping with 1,000 replicates was used to estimate 95% confidence intervals of the performance metrics, with photography as the resampling unit. On the subject-level classification, the network achieved the AUC of 0.976 (95% CI 0.965-0.988) among Asian population and 0.892 (95% CI 0-763-1.000) among Caucasian population. Conclusions Preliminary results show that this DLS performed well in identifying probable asymptomatic COVID-19 cases through the analysis of participants' eyes pictures. This method could be an innocuous, accessible, low cost and quick COVID-19 screening method. Eventually, it could potentially contribute to pandemic control. Key messages In the context of the COVID-19 pandemic it would be useful to have a screening method to easily and quickly detect asymptomatic individuals, in addition to using temperature control. Preliminary results show that this Deep Learning System (DLS) based on eyes pictures taken with mobile phone cameras could be an innocuous, accessible, low cost and quick COVID-19 screening method.

BACKGROUND Dupilumab is an antibody against interleukin-4 receptor α, used in the treatment of atopic dermatitis (AD). OBJECTIVES To evaluate the efficacy and safety of dupilumab in adult Chinese patients with moderate-to-severe AD. METHODS In this randomized, double-blind, placebo-controlled, parallel-group, phase III study, conducted between December 2018 and February 2020, patients with AD received dupilumab (300 mg) or placebo once every 2 weeks for 16 weeks, and were followed up for 12 weeks. The primary efficacy endpoint was the proportion of patients with both an Investigator's Global Assessment score of 0-1 and a reduction from baseline of ≥ 2 points at week 16. RESULTS Overall, 165 patients (mean age 30·6 years; 71·5% male patients) were randomized; 82 patients were randomized to dupilumab and 83 patients were randomized to placebo. At week 16, 26·8% of patients in the dupilumab group and 4·8% of patients in the placebo group achieved the primary endpoint [difference 22·0%, 95% confidence interval (CI) 11·37-32·65; P

The focal plane camera is the core component of the Wide Field-of-view Cherenkov/fluorescence Telescope Array (WFCTA) of the Large High-Altitude Air Shower Observatory (LHAASO). Because of the capability of working under moonlight without aging, silicon photomultipliers (SiPM) have been proven to be not only an alternative but also an improvement to conventional photomultiplier tubes (PMT) in this application. Eighteen SiPM-based cameras with square light funnels have been built for WFCTA. The telescopes have collected more than 100 million cosmic ray events and preliminary results indicate that these cameras are capable of working under moonlight. The characteristics of the light funnels and SiPMs pose challenges (e.g. dynamic range, dark count rate, assembly techniques). In this paper, we present the design features, manufacturing techniques and performances of these cameras. Finally, the test facilities, the test methods and results of SiPMs in the cameras are reported here., Comment: 45 pages, 21 figures, article

Tumor neoepitopes presented by major histocompatibility complex (MHC) class I are recognized by tumor-infiltrating lymphocytes (TIL) and are targeted by adoptive T-cell therapies. Identifying which mutant neoepitopes from tumor cells are capable of recognition by T cells can assist in the development of tumor-specific, cell-based therapies and can shed light on antitumor responses. Here, we generate a ranking algorithm for class I candidate neoepitopes by using next-generation sequencing data and a dataset of 185 neoepitopes that are recognized by HLA class I–restricted TIL from individuals with metastatic cancer. Random forest model analysis showed that the inclusion of multiple factors impacting epitope presentation and recognition increased output sensitivity and specificity compared to the use of predicted HLA binding alone. The ranking score output provides a set of class I candidate neoantigens that may serve as therapeutic targets and provides a tool to facilitate in vitro and in vivo studies aimed at the development of more effective immunotherapies. Robbins and colleagues develop and test a machine learning neoantigen ranking model using experimentally validated neoantigens from human tumors, providing a resource of targetable neoantigens for future immunotherapies.

Summary Aims The purpose of this study was to examine the effectiveness of beinaglutide on body weight, glycated haemoglobin (HbA1c), blood pressure and lipid profiles in patients with type 2 diabetes mellitus (T2DM) in a real‐world setting in China. Materials and methods This was a multicentre, observational, retrospective, open‐label study conducted in China. Data were collected from T2DM patients who started treatment with beinaglutide between 2017 and 2018. Results A total of 314 patients were included in the study. After 3 months of treatment with beinaglutide, there were significant reductions in body weight (−10.05 kg [95% confidence interval −9.29 to −10.80]), HbA1c (−2.87% [−2.62 to −3.11]), 2‐h postprandial plasma glucose (−5.46 mmol L−1 [−4.96 to −5.95]) and fasting plasma glucose (−3.04 mmol L−1 [−2.78 to −3.31]) (all p < 0.0001). In addition, 84.96% and 72.18% of the patients achieved weight loss of ≥5% and ≥10%, respectively. Subgroup analyses showed that weight loss was significantly greater in patients with ≥28 kg m−2 of baseline body mass index and 0.60 mg of beinaglutide doses (p = 0.007 and p < 0.0001, respectively). HbA1c reductions were significantly greater in patients with ≥9.0% baseline HbA1c and in those administered 0.40–0.48 mg of beinaglutide doses (all p < 0.0001). Weight loss at 3 months was positively correlated with baseline BMI and the dose of beinaglutide. Positive determinants for HbA1c reduction after 3 months were baseline HbA1c and the dose of beinaglutide. Conclusions These observational results confirmed the benefits of beinaglutide in weight loss and glycaemic control and support the use of beinaglutide as an effective treatment for T2DM.

Route planning and navigation in indoor space have become a hot topic recently. To accomplish this task, a map and a real-time detection system are needed. Due to Lidar systems’ high efficiency in data acquisition, Lidar sensors have become an indispensable part of an object detection system. In this paper, we use Lidar points to generate obstacle maps. The obstacle maps can be used as a reference for route planning and navigation. To identify single objects more precisely, a deep network combined PointNet with Markov Random Field (MRF) is designed in our work to classify Lidar points. Then, single objects are segmented by using the Euclidean clustering method. After that, the prior rules and derived criteria we summarized from large amount images are used to determine objects’ kind between Influence Movement Obstacles (IMO) and Non-Influence Movement Obstacles (N-IMO). Finally, objects are projected into a 2D plane to generate obstacle maps. To evaluate the performance of our method, experiments were performed on the S3DIS dataset of Stanford University. The results show that our method greatly improves the overall accuracy compared to the original PointNet model, and can generate high-quality obstacle maps.

Background The present diagnostic methods for detecting graft damage after kidney transplantation are either invasive or not available early enough. The microRNAs (miRNAs) in peripheral blood mononuclear cells (PBMCs) have been suggested as promising biomarkers. Methods Using quantitative real-time polymerase chain reaction, we identified 9 miRNAs (miR-142-5p, miR-142-3p, miR-223, miR-211, miR-486, miR-155, miR-10b, miR-30a, and let-7c) related to the human renal allograft status in PBMCs from 104 kidney transplant recipients. Results The miR-142-5p, miR-142-3p, and miR-223 were significantly upregulated and miR-10b was significantly downregulated in recipients with abnormal levels of serum creatinine 3 to 4 weeks after initial sample collection. Moreover, the miR-142-5p and miR-142-3p were also found to be significantly upregulated in recipients with abnormal levels of cystatin C. Through a combination of the validated miRNAs, receiver operating characteristic analyses yielded the highest area under the curve value of 0.7913 and 0.7063 in predicting the levels of serum creatinine and cystatin C, respectively. In the testing stage, the developed models correctly predicted allograft function in 16 to 17 of 22 recipients (false rate, 22.7%-27.2%). Conclusions miRNAs in PBMCs of recipients hold great promise to be used as predictive and noninvasive biomarkers after transplantation.

AIM To evaluate the association between volume ratio of the mucus pool and tumour response to neoadjuvant therapy in patients with mucinous rectal adenocarcinoma (MC). MATERIALS AND METHODS The volume of the mucus pool and whole tumour on pre-therapeutic T2-weighted magnetic resonance imaging (MRI) of 79 patients was measured using semi-automated software. Mucus pool volume, whole tumour volume, and volume ratio of the mucus pool were compared to tumour response and tumour and lymph node downstaging after neoadjuvant therapy using receiver operating characteristic curve (ROC) and multivariate logistic regression analysis. RESULTS After preoperative neoadjuvant therapy of rectal MC, the rate of pathological complete response, tumour downstaging, tumour response, and lymph node downstaging were 9%, 48%, 39% and 58%, respectively. Tumour downstaging more frequently occurred in patients with a mucus pool volume ratio of at least 68.3% (area under the ROC curve [AUC], 0.793 with 95% confidence interval [CI]: 0.693–0.893), and at least 62.1% for identifying those with a higher tumour response with an AUC of 0.739 (95% CI: 0.630–0.847). CONCLUSION A higher volume ratio of mucus pool in patients with MC may be related to more tumour downstaging and therapy response, and therefore, could serve as an independent imaging biomarker for predicting tumour response to neoadjuvant therapy.

Background We investigated a simple, novel diagnostic test for detecting incomplete effort during the motor portion of the neurological examination. Methods The results from the honest palm sign (HPS) were evaluated for 162 consecutive neuro-oncology patients who had undergone upper extremity strength testing. Deltoid, bicep, and wrist extensor strength was assessed in all patients. During the examination, patients were repeatedly encouraged to “try as hard as possible” and to “resist with all your strength.” The absence of nail prints on the palms constituted a positive HPS test result (i.e., indicative of incomplete effort). The presence of nail prints constituted a negative HPS test result (i.e., indicative of full effort). Results A total of 162 patients were tested. Their mean age was 55.5 ± 14.9 years, the median Karnofsky performance scale score was 80 (range, 60–100), and 63 patients (39%) were men. Of the 162 patients, 102 (63%) had malignant gliomas, 28 (17%) had brain metastases, 21 (13%) had other primary brain tumors, and 11 (6.8%) had primary central nervous system lymphomas. Of the 162 patients, 48 (30%) had positive HPS test results. The test sensitivity (84.6%), specificity (75.2%), positive likelihood ratio (3.41), and negative likelihood ratio (0.205) were good. After excluding 33 patients with characteristics that rendered them unsuitable for testing, the results from the remaining 129 patients were analyzed. The sensitivity was unchanged (84.6%), but the specificity (96.6%), positive likelihood ratio (24.5), and negative likelihood ratio (0.16) improved dramatically. Conclusions The HPS test is a simple, sensitive, and very specific test for detecting incomplete effort during the motor portion of neurological evaluations.

Approximately, 30% patients after radical prostatectomy (RP) will undergo post-operative biochemical recurrence (BCR). Present stratification method by TNM staging and Gleason score was not adequate to screen high-risk patients. In this study, we intended to identify a novel set of differentially expressed gene (DEG) signature that can predict BCR after RP. 358 patients after RP with follow-up data were extracted from The Cancer Genome Atlas (TCGA), among which 61 patients had undergone BCR. Key DEGs were confirmed by the intersection of GSE35988 and TCGA_PCa dataset, and their gene expression data were also extracted from TCGA_PCa dataset. Kaplan–Meier plot and Cox proportion hazard regression model were applied to assess the relationship between risk score and survival outcome (BCR). 310 DEGs were confirmed in two prostate cancer dataset. 6 DEGs (SMIM22, NINL, NRG2, TOP2A, REPS2, and TPCN2) were selected to construct a risk score formula. The risk score was a powerful predictive factor independent of TNM stage (HR 3.045, 95% CI 1.655–5.602, p

In this paper, we present a solution-region-based synthesis approach for selecting optimal four-bar linkages with a Ball–Burmester point. We discuss both general and special cases of the Burmester point that coincide with the Ball point at the pole of the inflection circle. Given the coordinates of one fixed joint, any point on the target's straight line, and the direction of this straight line, we can synthesize an infinite number of mechanisms using a coupler curve with five-point contacts with its tangent by adopting the proposed approach. Each initial parameter corresponds to three side links that can generate three four-bar mechanisms. We generate different mechanism property charts by developing mechanism software that enables users to intuitively identify relevant linkage information and select the optimal linkage. This novel approach is a visualized analytical method for synthesizing and selecting optimal four-bar linkages with one Ball–Burmester point on its coupler curve.

Purpose/Objective(s) Standard of care for locally advanced anal carcinoma is definitive chemoradiation with IMRT. Currently, target and organ-at-risk (OAR) volumes are created using a pre-treatment CT-simulation scan. However, during the course of radiotherapy, there is often change in the size and/or position of the tumor and surrounding normal structures. Therefore, we hypothesize that the implementation of an adaptive radiation therapy treatment protocol in anal cancer may reduce radiation dose to critical surrounding normal structures, such as the bowel, through the use of anatomy-adapted replanning. Materials/Methods Retrospective daily adaptive CTs were created for 4 patients (54 Gy, 30 fraction VMAT) in an oncology imaging informatics system using the Adaptive Calculation and Tracking for Offline Plan Review (ACTOR) toolkit. Each adaptive CT was created by deformable image registration (dir) of the planning CT to the daily CBCT. The structure sets from the planning CT were deformed onto each adaptive CT and ultimately corrected and revised by two qualified radiation oncologists. The adaptive CTs were transferred to a treatment planning system for recalculation. The original treatment plan was recalculated on each fraction adaptive CT to establish the real dose received during treatment. A two-sample t-test was used to compare the average real dose received dosimetric values to the values obtained on trigger-based adaptive planning. Results Using dose prescriptions for target volumes and normal tissue dose constraints as defined in RTOG 0529 (Kachnic et al 2013), normal bowel dose metrics, including bowel V45 20cc as trigger 1, there was a significant reduction in bowel V45 for each patient (table), with an average reduction in bowel V45 of 86.7% (P = 0.0001) across all patients. Adapting only the 5 fractions with the highest values for bowel V45 (trigger 2), we also found a significant reduction for each patient (table), with an average reduction of 20.8 % (P = 0.0011) across all patients. Conclusion Our study demonstrated that triggered adaptive re-planning using bowel V45 > 20cc could likely achieve reductions in normal tissue dose. Adaptive planning during radiation treatment of anal cancer may therefore be beneficial for reduction of treatment-related GI toxicity. These results can help inform a future randomized trial of adaptive therapy vs. standard planning.

Purpose/Objective(s) In this study, we developed a deep learning model to achieve automatic multi-target delineation on planning CT (pCT) and daily Cone-Beam CT (CBCT). To improve the image quality of the CBCT for accurate target delineation and dose calculation, we introduce an unsupervised learning model to generate the artifact-free synthetic CT (sCT) from the CBCT. The geometric and dosimetric impact of the model on planning CT (pCT) and synthetic CT (sCT) was evaluated for breast cancer adaptive radiation therapy. Materials/Methods We retrospectively analyzed 1127 patients treated with radiotherapy after breast-conserving surgery from two medical institutions. The CBCT for patient setup acquired utilizing breath-hold guided by optical surface monitoring system was used to generate sCT with the generative adversarial network. Organs at risk (OARs) and target volumes including tumor bed (TB) and clinical target volume (CTV) for breast cancer were delineated automatically with 3D U-Net model on pCT and sCT. The automatic delineation was compared with manually delineated contours to evaluate the performance with geometric metrics, including Dice similarity coefficient (DSC) and 95% Hausdorff Distance (HD95). The treatment plan which was transferred to the sCT from the pCT was generated with the same planning parameters as the original pCT-based plan. The dosimetric evaluation was performed by a quick dose recalculation on sCT relying on gamma analysis and the dose-volume histogram (DVH) parameters. The automatically delineating CTV on sCT which was rigidly registered to pCT was compared with manually delineating CTV on pCT to obtain DSC-CTV. The relationship between the ∆D95, ∆V95 and DSC-CTV was assessed to quantify the clinical impact of the geometric changes of CTV. Results The range of the DSC and HD95 were 0.73-0.97, 2.22-9.36mm for pCT, 0.63-0.95, 2.30-19.57mm for sCT from institution A, 0.70-0.97, 2.10-11.43mm for pCT from institution B respectively. The quality of sCT was excellent with an average mean absolute error (MAE) of 71.58 ± 8.78HU. The mean gamma pass rate (3%/3 mm criterion) by comparing the dose on sCT with that on original pCT was 91.46 ± 4.63%. DSC-CTV down to 0.65 accounted for a variation of more than 6% of V95 and 3Gy of D95. DSC-CTV up to 0.80 accounted for a variation of less than 4% of V95 and 2Gy of D95. The mean ∆V95 of CTV was less than 6%. The mean ∆V95 of TB was more than 8%. The mean ∆D90/∆D95 of CTV and TB were less than 2Gy/4Gy, 4Gy/5Gy for all the patients. The cardiac dose difference in left breast cancer was bigger than that in right breast cancer. Conclusion This study demonstrates that highly accurate multi-target delineation and dose calculation are achievable using the daily CBCT image via deep learning. The results show that dose distribution needs to be considered to evaluate the clinical impact of geometric variations to decide whether to re-plan during breast cancer radiotherapy.

Vertical field-effect transistor (VFET) structure has the advantage in improving both the breakdown voltage (BV) and on-resistance (RON) of semiconductor power devices when compared with the lateral devices. GaN-based normally-off VFET device is designed and demonstrated in this work and an additional back current block layer (B-CBL) is proposed and employed to further improve the device performances. By introducing the B-CBL design, the electric field distribution along the gate aperture is more uniform which leads to an obvious increase (~30%) of BV in the proposed device while the RON is kept nearly constant. Therefore, the figure of merit (FOM) value of the proposed VFET is improved apparently in comparison with that of the conventional GaN-based VFET devices.

In this study, we sought to characterize synovial tissue obtained from individuals with arthralgia and disease-specific auto-antibodies, and patients with established rheumatoid arthritis (RA) by applying an integrative multi-omics approach where we investigated changes at the level of DNA methylation and gene expression and its relation to disease pathogenesis. We performed genome-wide DNA methylation and gene expression profiling of synovial tissue obtained from the knee and ankle from 4 auto-antibody positive arthralgia patients and thirteen RA patients. Through multi-omics factor analysis we observed that the latent factor explaining the variance in gene expression and DNA methylation was associated with Swollen Joint Count 66 (SJC66) where patients with SJC66 of 9 or more displayed reasonable separation from the rest. Specifically, combined DNA methylation and gene expression patterns of patients with SJC66 ≥ 9 displayed activation of the immune response as well as dysregulation of cell adhesion pathways. Through an integrative analysis framework, we reveal differences in both methylation and expression at 59 genes associated with the difference between SJC66 ≥ 9 and 0 < SJC66 ≤ 8, for which we identify specific transcripts correlated with differential methylation. Our results highlight the utility of genome-wide multi-omics profiling of synovial samples for improved understanding of the changes associated with an increasing number of swollen joints in RA patients, and point to novel candidate targets for the treatment of the disease. Funding Statement: AYFLY was funded by the European Union’s Horizon 2020 research and innovation program under Grant Agreement No. ITN-2014-EID-641665. Declaration of Interests: AYFLY, KM, GR, EC, HDL, DFT, CL, DG, and RB are employees of GSK. EF and PPT are employees of Novartis and Kintai Therapeutics, respectively. WJJ is financially supported by GSK and Mead Johnson. All declarations are correct for the time of writing and/or conducting this study. Ethics Approval Statement: All subjects provided written informed consent and the collection and use of the samples received Institutional Review Board review and approval. Characteristics of patients included in this study are listed in Table S1.

Background: Ultraviolet-C (UV-C) light devices are effective in reducing contamination on N95 filtering facepiece respirators. However, limited information is available on whether UV-C devices meet the Food and Drug Administration’s (FDA) microbiological requirements for Emergency Use Authorization (EUA) for respirator bioburden reduction. Methods: We tested the ability of 2 UV-C light boxes to achieve the 3-log10 microorganism reductions required for EUA for reuse by single users. Whole 3M 1860 or Moldex 1513 respirators were inoculated on the exterior facepiece, interior facepiece, and internal fibers with bacteriophage MS2 and/or 4 strains of bacteria and treated with UV-C cycles of 1 or 20 minutes. Colorimetric indicators were used to assess penetration of UV-C through the respirators. Results: For 1 UV-C box, a 20-minute treatment achieved the required bioburden reduction for Moldex 1513 but not 3M 1860 respirators. For the second UV-C box, a 1-minute treatment achieved the required bioburden reduction in 4 bacterial strains for the Moldex 1513 respirator. Colorimetric indicators demonstrated penetration of UV-C through all layers of the Moldex 1513 respirator but not the 3M 1860 respirator. Conclusions: Our findings demonstrate that UV-C box technologies can achieve bioburden reductions required by the FDA for EUA for single users but highlight the potential for variable efficacy for different types of respirators.

We present the calibration strategy for the 20 kton liquid scintillator central detector of the Jiangmen Underground Neutrino Observatory (JUNO). By utilizing a comprehensive multiple-source and multiple-positional calibration program, in combination with a novel dual calorimetry technique exploiting two independent photosensors and readout systems, we demonstrate that the JUNO central detector can achieve a better than 1% energy linearity and a 3% effective energy resolution, required by the neutrino mass ordering determination. [Figure not available: see fulltext.], 0, info:eu-repo/semantics/published