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Background: This study aimed to assess the safety and immunogenicity of MVC-COV1901, a recombinant COVID-19 protein vaccine, containing S-2P protein adjuvanted with CpG 1018 and aluminum hydroxide, for people living with HIV (PWH). Methods: A total of 57 PWH of ≥20 years of age who are on stable antiretroviral therapy were compared with 882 HIV-negative participants. Participants received two doses of MVC-COV1901 28 days apart. Results: No vaccine-related serious adverse events (SAEs) were recorded. Seroconversion rates (SCRs) of 100% and 99.8% were achieved in PWH and comparators, respectively, 28 days after the second dose. After adjusting for sex, age, BMI category, and comorbidity, the adjusted GMT ratio of comparator/PWH was 3.2 (95% CI 2.5–4). A higher CD4/CD8 ratio was associated with a higher GMT (R = 0.27, p = 0.039). MVC-COV1901 has shown robust safety but elicited weaker immune responses in PWH. Conclusions: Further investigations may be needed to determine whether PWH require distinct immunization strategies with improved immunogenicity. The main study is registered at ClinicalTrials.gov (NCT04695652).

To explore how parents of children with cancer offer educational supports during the treatment process.Based on a descriptive qualitative method design, 29 mothers and 19 fathers of children with cancer were interviewed on their experiences of supporting their child's education during their child's treatment through semi-structured interviews.Six themes were summarized from the parents' experiences in supporting their child's education during treatment: initial emphasis on survival over education; educational strategies important when returning to everyday life post-treatment; parents and educators have different expectations; child's extracurricular activities provided a sense of accomplishment; preparing for transition to school; and long-term concern was for the child's health and happiness.Education is part of children's normal development, but education is often placed on hold for a child receiving cancer treatment. Parents of children with cancer are unable to focus on the child's education because of the threat to their child's life. When their child's illness stabilizes, they will begin to utilize their resources to arrange lessons to facilitate returning to school. Through understanding parents' learning expectations, medical professionals can support adjustments to parents' attitudes.

Full list of authors: Kim, Minbin; Ripa, Jakub; Park, Il H.; Bogomolov, Vitaly; Brandt, Søren; Budtz-Jørgensen, Carl; Castro-Tirado, Alberto J.; Chang, Sheng-Hsiung; Chang, Yenyun; Chen, Chia Ray; Chen, C. -W.; Chen, Pisin; Connell, Paul; Eyles, Chris; Gaikov, Georgii; Hong, Gihan; Huang, Jian Jung; Huang, Ming-Huey Alfred; Jeong, Soomin; Kim, Jieun; Lee, Jik; Lim, Heuijin; Lin, Chih-Yang; Liu, Tsung-Che; Nam, Jiwoo; Panasyuk, Mikhail; Petrov, Vasily; Reglero, Victor; Rodrigo, Juana M.; Svertilov, Sergey; Vedenkin, Nikolay; Wang, Ming Zu; Yashin, Ivan.--This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited., We developed an X-ray detector using 36 arrays, each consisting of a 64-pixellated yttrium oxyorthosilicate (YSO) scintillation crystal and a 64-channel multi-anode photomultiplier tube. The Xray detector was designed to detect X-rays with energies lower than 10 keV, primarily with the aim of localizing gamma-ray bursts (GRBs). YSO crystals have no intrinsic background, which is advantageous for increasing low-energy sensitivity. The fabricated detector was integrated into UBAT, the payload of the Ultra-Fast Flash Observatory (UFFO)/Lomonosov for GRB observation. The UFFO was successfully operated in space in a low-Earth orbit. In this paper, we present the responses of the X-ray detector of the UBAT engineering model identical to the flight model, using241 Am and55 Fe radioactive sources and an Amptek X-ray tube. We found that the X-ray detector can measure energies lower than 5 keV. As such, we expect YSO crystals to be good candidates for the X-ray detector materials for future GRB missions. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland., This study was supported by grants from the Korean National Research Foundation (NRF-2017K1A4A3015188, NRF-2021R1A2B5B03002645, and NRF-2019H1D3A2A02060090). The Russian work was partially supported by ROSCOSMOS grants and by RFFI grant No. 13-02-12175 and No.15-35-21038 and support from the Development Program of Lomonosov Moscow State University is acknowledged. AJCT acknowledges support from the Spanish MINECO Projects AYA 2009-14000-C03-01/ESP and AYA2015-1718-R (including EU/FEDER funds). The authors thank Taiwan’s National Science Council Vanguard Program (100-2119-M-002-025) and Ministry of Science and Technology (MOST) for the funding (104-2811-M-002-160). MBK acknowledges the support from NRF-2015-GPF., With funding from the Spanish government through the Severo Ochoa Centre of Excellence accreditation SEV-2017-0709.

Cu-Cu joints have potential in high performance electric product. Although the voids in the bonding interface was observed, there was no report on the size distribution and evolution of voids due to ripening. In this paper, the void size distribution under 200 °C for 30, 60 and 120 min is obtained by a specific direction. The average void diameter is 49 nm, 70 nm, and 96 nm for the joint annealed for 30, 60, and 120 min, respectively. A simple kinetic model of ripening is developed, and the relationship between radius and annealing time is in good agreement with experimental data.

Mesoporous silica (SiO2) nanoparticles were prepared using the cationic surfactant cetyltrimethylammonium bromide as a soft template in a basic medium. The particles were coated with a carbon layer through a facile hydrothermal process. The carbon-coated mesoporous SiO2 (C#SiO2) nanoparticles were used as core for the in situ chemical-oxidative polymerization of conductive polypyrrole (PPy). The structure and morphology of the PPy/C#SiO2 nanocomposites were analyzed by transmission electron microscopy, wide-angle X-ray diffraction, and Fourier transform infrared spectroscopy. A glassy carbon electrode was modified with the PPy/C#SiO2 nanocomposites. The performance of the modified electrode for the dopamine (DA) detection was examined by cyclic voltammetry, electrochemical impedance spectroscopy, and differential pulse voltammetry. The modified PPy/C#SiO2 glassy carbon electrode exhibit large peak currents for the DA oxidation reaction, suggesting the electrochemical performance of the nanocomposites is enhanced. The impedance evaluation of the fabricated PPy/C#SiO2 nanocomposites reveals a very small charge-transfer resistance. Additionally, the nanocomposites showed a linear response for DA detection in the concentration range of 1 × 10−6 to 2 × 10−4 M with a detection limit of 7.6 × 10−7 M (S/N = 3). Moreover, DA detection was successful in the presence of uric acid and l-ascorbic acid. Due to their outstanding electrochemical performance, the PPy/C#SiO2 nanocomposites may be considered for the DA detection devices.

Highlights • It is difficult to visualize extra-hepatic biliary anatomy clearly because of long-presence of ICG in liver when administered intravenously. • Intracholecystic ICG injection illuminates extra-hepatic biliary tree preferentially thus reducing background hepatic noise. • Surgeons can experience more satisfaction with the use of fluorescent cholangiography during laparoscopic cholecystectomy when the intracystic route of ICG administration is utilized., Introduction The utility of intracystic administration of indocyanine green for near-infrared fluorescent cholangiography in acute calculous cholecystitis initially treated with percutaneous transhepatic gallbladder drainage (PTGBD) was described in this report. Presentation of case Two cases who underwent near-infrared fluorescent cholangiography guided interval laparoscopic cholecystectomy two weeks post-PTGBD were studied retrospectively. Both patients were diagnosed with moderate acute calculous cholecystitis based on diagnostic criteria of the Tokyo guidelines. Two routes of indocyanine green administration were utilized during surgery, first through direct intracystic administration through PTGBD tube (5 ml of 12.5 mg ICG) to achieve critical view of safety and then intravenous administration (1 ml of 2.5 mg ICG) to visualize cystic artery. Discussion Both patients had critical view of safety visualized clearly with ICG with the operation time of 84 and 125 min in cases 1 and 2, respectively without any intra or postoperative complications. Conclusion In comparison with intravenous ICG administration, trans-PTGBD ICG route can provide better signal-to-noise ratio by avoiding hepatic fluorescence and thus increasing the bile duct to liver contrast. However, ICG may enter the lymphatic system through necrotic and inflammatory gallbladder mucosa, of which lymph spillage during gallbladder dissection can obscure the fluorescent view.

One major aspect of the aging process is the onset of chronic, low-grade inflammation that is highly associated with age-related diseases. The molecular mechanisms that regulate these processes have not been fully elucidated. We have identified a spontaneous mutant mouse line, small with kinky tail (skt), that exhibits accelerated aging and age-related disease phenotypes including increased inflammation in the brain and retina, enhanced age-dependent retinal abnormalities including photoreceptor cell degeneration, neurodegeneration in the hippocampus, and reduced lifespan. By positional cloning, we identified a deletion in chondroitin sulfate synthase 1 (Chsy1) that is responsible for these phenotypes in skt mice. CHSY1 is a member of the chondroitin N-acetylgalactosaminyltransferase family that plays critical roles in the biosynthesis of chondroitin sulfate, a glycosaminoglycan (GAG) that is attached to the core protein to form the chondroitin sulfate proteoglycan (CSPG). Consistent with this function, the Chsy1 mutation dramatically decreases chondroitin sulfate GAGs in the retina and hippocampus. In addition, macrophage and neutrophil populations appear significantly altered in the bone marrow and spleen of skt mice, suggesting an important role for CHSY1 in the functioning of these immune cell types. Thus, our study reveals a previously unidentified impact of CHSY1 in the retina and hippocampus. Specifically, chondroitin sulfate (CS) modification of proteins by CHSY1 appears critical for proper regulation of immune cells of the myeloid lineage and for maintaining the integrity of neuronal tissues, since a defect in this gene results in increased inflammation and abnormal phenotypes associated with age-related diseases.

Since nearly all studies concerning the approximate Crank–Nicolson perfectly matched layer (CN-PML) are limited to 2-D cases, a computationally efficient implementation that can be used to truncate 3-D finite-difference time-domain (FDTD) lattices is presented in this article. More precisely, it is based on the CN direct-splitting (DS) scheme and the bilinear transform (BT) method. This article can fully exploit the unconditional stability of the standard CN-FDTD method and can be free from the Courant–Friedrich–Lewy (CFL) limit; hence, it is especially suitable for situations where space discretization step is much smaller than 1/10th or 1/20th of the smallest wavelength of interest. Aiming at further reducing the requirement of the computer resources, this new implementation can be reformulated in more simple forms if proper auxiliary variables are introduced. It therefore shows a higher iteration speed than other published unconditionally stable PMLs as fewer numbers of arithmetic operations are involved. Finally, three numerical examples, including scatting, transmission, and radiation, are also provided to validate its running time, unconditional stability, and absorption characteristic.

The Old World genus Thysanarthria Orchymont, 1926 is reviewed taxonomically and compared to the related genus Chaetarthria Stephens, 1835. Chaetarthria is considered to consist of three groups differing in the morphology of male genitalia and surrounding sclerites: (1) large Old World Chaetarthria which seems to stand apart of the remaining groups, and (2) European Chaetarthria plus (3) American Chaetarthria which both share the male sternite 8 with a long median projection with Thysanarthria. The reduced mesal part of male sternite 9 is shared by European Chaetarthria and Thysanarthria, supporting their close relationship proposed by previous molecular analyses. Sixteen species are recognized within Thysanarthria which differ in the details of the morphology of the aedeagus illustrated for all species. Seven species are described as new: T. bifida sp. nov. (Thailand), T. cardamona sp. nov. (India: Kerala), T. chui sp. nov. (Taiwan), T. persica sp. nov. (southern Iran), T. saurahana sp. nov. (Nepal), T. trifida (Laos), and T. wadicola sp. nov. (Oman). New records are provided for T. ceylonensis Hebauer, 2001 (new to India: Madhya Pradesh), T. championi (Knisch, 1924) (new to Afghanistan, India: Arunachal Pradesh, China: Yunnan, and Myanmar), T. madurensis Hebauer, 2001 (new to Nepal and India: Kerala), and T. siamensis Hebauer, 2001 (new to India: Uttarkhand, Nepal and Laos). Chaetarthriomorphus sulcatus Chiesa, 1967 is revealed as a junior synonym of Chaetarthria championi Knisch, 1924, and lectotypes are designated for both these taxa. An undescribed species of the American group of Chaetarthria is recorded from Saudi Arabia either as an accidental introduction or due to mislabeling; the species is illustrated but not described.

To investigate the role of sonic hedgehog (Shh) signaling and epithelial–mesenchymal transition (EMT) in bladder cancer progression and invasion. We cultured three bladder cancer cell lines, muscle-invasive T24 and 5637, and non-muscle-invasive KK47, in the presence of a recombinant-Shh (r-Shh) protein or cyclopamine, a Shh signaling inhibitor, to investigate proliferation and expression of EMT markers. Wound-healing assays and transwell assay were performed to evaluate cell invasion and migration. Mice were then inoculated with bladder cancer cells and treated with cyclopamine. Mouse tumor samples were stained for Shh signaling and EMT markers. R-Shh protein enhanced cell proliferation, whereas cyclopamine significantly suppressed cell proliferation, especially in invasive cancer (5637 and T24) (p

Owing to their small interaction cross-section, neutrinos are unparalleled astronomical tracers. Ultra-high energy (UHE; E > 10 PeV) neutrinos probe the most distant, most explosive sources in the Universe, often obscured to optical telescopes. Radio-frequency (RF) detection of Askaryan radiation in cold polar ice is currently regarded as the best experimental measurement technique for UHE neutrinos, provided the RF properties of the ice target can be well-understood. To that end, the Askaryan Radio Array (ARA) experiment at the South Pole has used long-baseline RF propagation to extract information on the index-of-refraction ( n = ϵ r ) in South Polar ice. Owing to the increasing ice density over the upper 150–200 m, rays are measured along two, nearly parallel paths, one of which refracts through an inflection point, with differences in both arrival time and arrival angle that can be used to constrain the neutrino properties. We also observe (first) indications for RF ice birefringence for signals propagating along predominantly horizontal trajectories, corresponding to an asymmetry of order 0.1% between the ordinary and extra-ordinary birefringent axes, numerically compatible with previous measurements of birefringent asymmetries for vertically-propagating radio-frequency signals at South Pole. Qualitatively, these effects offer the possibility of redundantly measuring the range from receiver to a neutrino interaction in Antarctic ice, if receiver antennas are deployed at shallow (z ∼ −25 m) depths. Such range information is essential in determining both the neutrino energy, as well as the incident neutrino direction.

Nonlinear electromagnetic (EM) inverse scattering is a quantitative and super-resolution imaging technique, in which more realistic interactions between the internal structure of scene and EM wavefield are taken into account in the imaging procedure, in contrast to conventional tomography. However, it poses important challenges arising from its intrinsic strong nonlinearity, ill-posedness, and expensive computation costs. To tackle these difficulties, we, for the first time to our best knowledge, exploit a connection between the deep neural network (DNN) architecture and the iterative method of nonlinear EM inverse scattering. This enables the development of a novel DNN-based methodology for nonlinear EM inverse problems (termed here DeepNIS). The proposed DeepNIS consists of a cascade of multi-layer complexvalued residual convolutional neural network (CNN) modules. We numerically and experimentally demonstrate that the DeepNIS outperforms remarkably conventional nonlinear inverse scattering methods in terms of both the image quality and computational time. We show that DeepNIS can learn a general model approximating the underlying EM inverse scattering system. It is expected that the DeepNIS will serve as powerful tool in treating highly nonlinear EM inverse scattering problems over different frequency bands, involving large-scale and high-contrast objects, which are extremely hard and impractical to solve using conventional inverse scattering methods.

Extraosseous Ewing's sarcoma is a rare tumor which is aggressive with poor prognosis; it can occur anywhere in the body, but scantily in the pancreas. Pancreatic Ewing's sarcoma is not reported commonly, with inconsistent clinical manifestations. In this regard, early recognition of this disease is very important for the patient's sake.A 16-year-old boy presented with left lower quadrant abdominal pain for 2 months, and left flank pain with dysuria for 1 month.Abdominal and renal ultrasonography found a mass between the spleen and left kidney as well as left renal pelvic dilatation. Abdominal computed tomography found a heterogenous mass derived from the tail of the pancreas. Serial examinations revealed that the mass was a pancreatic Ewing's sarcoma. Furthermore, no metastasis was documented.The tumor was totally excised after 6 months of chemotherapy, which included 10 courses of neoadjuvant chemotherapy with vincristine, epirubicin, and cyclophosphamide, alternating with ifosfamide and etoposide. The patient completed consolidation chemotherapy with vincristine, epirubicin, and cyclophosphamide, alternating with ifosfamide and etoposide for 5 courses. Radiotherapy was applied to the tumor-involved region and tumor bed.To date, the malignancy has not recurred since the treatment was completed 4 years ago. There are no complications from the treatment for the patient.The pancreas is a very rare extraosseous location for Ewing's sarcoma. Pancreatic extraosseous Ewing's sarcoma should be regarded as a differential diagnosis of non-urinary originated left flank pain with dysuria in adolescents.

The TAROGE-M radio observatory is a self-triggered antenna array on top of the ∼2700 m high Mt. Melbourne in Antarctica, designed to detect impulsive geomagnetic emission from extensive air showers induced by ultra-high energy (UHE) particles beyond 1017 eV, including cosmic rays, Earth-skimming tau neutrinos, and particularly, the “ANITA anomalous events” (AAE) from near and below the horizon. The six AAE discovered by the ANITA experiment have signal features similar to tau neutrinos but that hypothesis is in tension either with the interaction length predicted by Standard Model or with the flux limits set by other experiments. Their origin remains uncertain, requiring more experimental inputs for clarification. The detection concept of TAROGE-M takes advantage of a high altitude with synoptic view toward the horizon as an efficient signal collector, and the radio quietness as well as strong and near vertical geomagnetic field in Antarctica, enhancing the relative radio signal strength. This approach has a low energy threshold, high duty cycle, and is easy to extend for quickly enlarging statistics. Here we report experimental results from the first TAROGE-M station deployed in January 2020, corresponding to approximately one month of livetime. The station consists of six receiving antennas operating at 180–450 MHz, and can reconstruct source directions of impulsive events with an angular resolution of ∼0.3°, calibrated in situ with a drone-borne pulser system. To demonstrate TAROGE-M's ability to detect UHE air showers, a search for cosmic ray signals in 25.3-days of data together with the detection simulation were conducted, resulting in seven identified candidates. The detected events have a mean reconstructed energy of 0.95-0.31 +0.46 EeV and zenith angles ranging from 25° to 82°, with both distributions agreeing with the simulations, indicating an energy threshold at about 0.3 EeV. The estimated cosmic ray flux at that energy is 1.2-0.9 +0.7 × 10-16 eV-1 km-2 yr-1 sr-1, also consistent with results of other experiments. The TAROGE-M sensitivity to AAEs is approximated by the tau neutrino exposure with simulations, which suggests comparable sensitivity as ANITA's at around 1 EeV energy with a few station-years of operation. These first results verified the station design and performance in a polar and high-altitude environment, and are promising for further discovery of tau neutrinos and AAEs after an extension in the near future.

Background and Objectives: Septins (SEPTs) are highly conserved GTP-binding proteins and the fourth component of the cytoskeleton. Polymerization of SEPTs contributes to several critical cellular processes such as cytokinesis, cytoskeletal remodeling, and vesicle transportation. In our previous study, we found that SEPT14 mutations resulted in teratozoospermia with >87% sperm morphological defects. SEPT14 interactors were also identified through proteomic assays, and one of the peptides was mapped to RAB3B and RAB3C. Most studies on the RAB3 family have focused on RAB3A, which regulates the exocytosis of neurotransmitters and acrosome reactions. However, the general expression and patterns of the RAB3 family members during human spermatogenesis, and the association between RAB3 and teratozoospermia owing to a SEPT14 mutation, are largely unknown. Materials and Methods: Human sperm and murine male germ cells were collected in this study and immunofluorescence analysis was applied on the collected sperm. Results: In this study, we observed that the RAB3C transcripts were more abundant than those of RAB3A, 3B, and 3D in human testicular tissues. During human spermatogenesis, the RAB3C protein is mainly enriched in elongated spermatids, and RAB3B is undetectable. In mature human spermatozoa, RAB3C is concentrated in the postacrosomal region, neck, and midpiece. The RAB3C signals were delocalized within human spermatozoa harboring the SEPT14 mutation, and the decreased signals were accompanied by a defective head and tail, compared with the healthy controls. To determine whether RAB3C is involved in the morphological formation of the head and tail of the sperm, we separated murine testicular tissue and isolated elongated spermatids for further study. We found that RAB3C is particularly expressed in the manchette structure, which assists sperm head shaping at the spermatid head, and is also localized at the sperm tail. Conclusions: Based on these results, we suggest that the localization of RAB3C proteins in murine and human sperm is associated with SEPT14 mutation-induced morphological defects in sperm.

In this review, the condensation HTCs (heat transfer coefficients) and pressure drop characteristics of some major low-global-warming-potential (GWP) refrigerants alternative to R-134a such as R-1234ze(E), R-1234ze(Z), R-1234yf, R-513A, and R-450A are reviewed. The thermofluids’ characteristics inside/outside a tube, minichannel, microfin tube, and plate heat exchanger are examined. In addition, several other refrigerants attributed to low GWP are also included in the present review. The experimental/numerical/simulation results’ analysis reveals that condensation HTCs and pressure drop characteristics depend on several parameters such as thermodynamics and transport properties of the working fluid, mass flux of the refrigerants, heat flux, saturation temperature, vapor quality, flow patterns, flow conditions, orientation of the condensing geometry, and condensation geometry (shape, size, and smooth/enhanced).

Castration-resistant prostate cancer (PCa; CRPC) has a poor response to androgen deprivation therapy and is considered an incurable disease. MicroRNA (miR)-lethal 7c (let-7c) was implied to be a tumor suppressor in PCa, and treatment with exogenous let-7c targets both cancer cells and their associated mesenchymal stem cells (MSCs) to prevent CRPC progression and metastasis. Exosomes are nanometer-sized membrane-bound vesicles which have an absolute predominance in biocompatibility for drug delivery and gene therapy by mediating cell-to-cell communication. By utilizing the intrinsic tumor-targeting property of MSCs, this study aimed to investigate the feasibility of MSC-derived exosomes as an exogenous miR delivery system to target CRPC, using miR let-7c as an example.Bioinformatics analysis was performed to observe miR-let-7c expression in clinical samples by utilizing the GEO database. MSC-derived exosomes were collected from a human bone marrow-derived MSC cell line after cell transfection with either a pre-miR negative control or pre-miR-let-7c, and further characterized through nanoparticle tracking analysis and Western blotting. miR-let-7c expression was determined using RT-qPCR, and the phenotypic effects of both naked and MSC-exosome-encapsulated let-7c on CRPC cells (PC3 and CWR22Rv1) were determined by WST-1 cell proliferation assay and wound healing migration assay.miR-let-7c was downregulated in metastatic PCa and high grade group patients. miR-let-7c expression was confirmed to be downregulated in PCa cell lines, with massively decreased in most metastatic CRPC-like cells. Exogenous miR-let-7c can be successfully packaged into MSC exosomes. Treatment with either naked or MSC-exosome-encapsulated miR-let-7c resulted in significant reductions in cell proliferation and migration in CRPC-like PC3 and CWR22Rv1 cells.MSC-derived exosomes could serve as a therapeutic let-7c delivery system to target CRPC.

SummaryBackgroundWe have assessed the safety and immunogenicity of the COVID-19 vaccine MVC-COV1901, a recombinant protein vaccine containing prefusion-stabilized spike protein S-2P adjuvanted with CpG 1018 and aluminium hydroxide.MethodsThis is a phase 2, prospective, randomised, double-blind, placebo-controlled, and multi-centre study to evaluate the safety, tolerability, and immunogenicity of the SARS-CoV-2 vaccine candidate MVC-COV1901. The study comprised 3,844 participants of ≥ 20 years who were generally healthy or with stable pre-existing medical conditions. The study participants were randomly assigned in a 6:1 ratio to receive either MVC-COV1901 containing 15 μg of S-2P protein or placebo containing saline. Participants received two doses of MVC-COV1901 or placebo, administered 28 days apart via intramuscular injection. The primary outcomes were to evaluate the safety, tolerability, and immunogenicity of MVC-COV1901 from Day 1 (the day of first vaccination) to Day 57 (28 days after the second dose). Immunogenicity of MVC-COV1901 was assessed through geometric mean titres (GMT) and seroconversion rates (SCR) of neutralising antibody and antigen-specific immunoglobulin. This clinical trial is registered at ClinicalTrials.gov: NCT04695652.FindingsFrom the start of this phase 2 trial to the time of interim analysis, no vaccine-related Serious Adverse Events (SAEs) were recorded. The most common solicited adverse events across all study participants were pain at the injection site (64%), and malaise/fatigue (35%). Fever was rarely reported (InterpretationMVC-COV1901 shows good safety profiles and promising immunogenicity responses. The current data supports MVC-COV1901 to enter phase 3 efficacy trials and could enable regulatory considerations for Emergency Use Authorisation (EUA).FundingMedigen Vaccine Biologics Corporation and Taiwan Centres for Disease Control.

Objective Determine long term (11 year) trends in gabapentin and pregabalin prescribing among workers' compensation claimants at various opioid dose combinations (low, medium, high, and very high) in Louisiana. Method A longitudinal study of 18,737 claimants who filled any prescriptions between 2008 and 2018. Results The proportion of claimants prescribed opioids alone at all dose levels decreased dramatically. The proportion claimants prescribed the combination of low dose opioids and low dose gabapentinoids increased (7.7% to10.9%). Prescribing higher daily doses of gabapentinoids was associated with higher daily doses of opioids. Gabapentinoid prescribing was associated with continued prescribing of medium and high dose opioids as claims matured. Conclusions Overall opioid prescribing decreased over time, while prescribing low dose opioids with gabapentinoids, increased.

Recently, programmable metasurfaces have aroused great attention for various applications such as beam manipulation, wireless communication, and holograms by modulating the spatial phase or amplitude. However, programmable amplitude‐coding modulations have rarely been investigated due to the difficulty in realizing dynamic control of amplitude. Herein, a real‐time programmable amplitude‐coding metasurface with multifrequency modulation is proposed by integrating PIN diodes and chip attenuators to the metaelement. The element is encoded as “11,” “10,” and “00,” corresponding to the ON/OFF states of two diodes. By switching the two states of the PIN diode, the metaelement exhibits distinctly reflected amplitude responses in three frequencies (2.98, 4.11, and 5.73 GHz). For the whole metasurface, the magnitude of the reflected beam can be modulated with some specific coding patterns. To verify the performance, six coding patterns with 10 × 10 metaelements are designed, and four of them are measured. Experimental results are fundamentally consistent with theoretical designs and simulations. Further a wireless communication demonstration is designed and implemented to perform direct modulation of digital signals without using mixers required in the conventional wireless communication systems. It is envisioned that this work will find applications in new architecture encrypted communication and imaging systems.

We present a portable calibration pulser system applied to radio antennas in order to detect ultra-high energy cosmic rays and neutrinos. The system consists of a solid-state high-voltage impulse generator, a digital attenuator, a wide band (150-350 MHz) bi-cone antenna, and a differential GPS. Taking an advantage of light weight of each component (less than $1.4$ kg), we developed an airborne calibration system by attaching them on a commercial drone. This system will be used for TAROGE experiment in high mountains as well as in Antarctica. We will report on its design, construction, performance, and potential applications for future radio experiments.

The Askaryan Radio Array (ARA) is a ground-based radio detector at the South Pole designed to capture Askaryan emission from ultra-high energy neutrinos interacting within the Antarctic ice. The newest ARA station has been equipped with a phased array trigger, in which radio signals in multiple antennas are summed in predetermined directions prior to the trigger. In this way, impulsive signals add coherently, while noise likely does not, allowing the trigger threshold to be lower than a traditional ARA station. Early results on just a fraction of available data from this new system prove the feasibility of a low-threshold analysis.

The Askaryan Radio Array (ARA) is an ultra-high energy (UHE) neutrino ($E_{\nu}$ > $10^{17}$ eV) detector at South Pole. ARA aims to utilize radio signals detected from UHE neutrino interactions in the glacial ice to infer properties about the interaction vertex as well as the incident neutrino. To retrieve these properties from experiment data, the first step is to extract timing, amplitude and frequency information from waveforms of different antennas buried in the deep ice. These features can then be utilized in a neural network to reconstruct the neutrino interaction vertex position, incoming neutrino direction and shower energy. So far, vertex can be reconstructed through interferometry while neutrino reconstruction is still under investigation. Here I will present a solution based on multi-task deep neural networks which can perform reconstruction of both vertex and incoming neutrinos with a reasonable precision. After training, this solution is capable of rapid reconstructions (e.g. 0.1 ms/event compared to 10000 ms/event in a conventional routine) useful for trigger and filter decisions, and can be easily generalized to different station configurations for both design and analysis purposes.

The TAROGE-M observatory is an autonomous antenna array on the top of Mt.~Melbourne ($\sim2700$ m altitude) in Antarctica, designed to detect radio pulses from ultra-high energy (over $10^{17}$ eV) air showers coming from near-horizon directions. The targeted sources include cosmic rays, Earth-skimming tau neutrinos, and most of all, the anomalous near-horizon upward-going events of yet unknown origin discovered by ANITA experiments. The detection concept follows that of ANITA: monitoring large area of ice from high-altitude and taking advantage of strong geomagnetic field and quiet radio background in Antarctica, whereas having significantly greater livetime and scalability. The TAROGE-M station, upgraded from its prototype built in 2019, was deployed in January 2020, and consists of 6 log-periodic dipole antennas pointing horizontally with bandwidth of 180-450 MHz. The station is then calibrated with drone-borne transmitter, with which the event reconstruction obtained $\sim0.3^\circ$ angular resolution. The station was then smoothly operating in the following month, with the live time of $\sim30$ days, before interrupted by a power problem, and its online filtering has identified several candidate cosmic-ray events and sent out via satellite communication. In this paper, the instrumentation of the station for polar and high-altitude environment, its radio-locating performance, the preliminary result on cosmic-ray detection, and the future extension plan are presented.

This study summarizes available data on karyotypes of water scavenger beetles (Coleoptera: Hydrophiloidea: Hydrophilidae), based on newly acquired data of 23 genera and 64 species. We combine these data with previously published data, which we review. In total, karyotypes are available for 33 genera and 95 species, covering all subfamilies and tribes. Available data indicate that most groups of the Hydrophilidae are diploid and sexually reproducing, with XY (♂) and XX (♀) sex chromosomes; the Y chromosome is always minute and does not recombine with X during meiosis. Exceptions are known in Anacaena, with parthenogenetic diploid or triploid populations in some species and sex chromosomes fused with autosomes in others. The diploid number of chromosomes is 2n = 18 in the subfamilies Acidocerinae, Chaetarthriinae, Enochrinae and Hydrophilinae. Variations are known in species of Anacaena and Berosus (both usually with 2n = 18) and in Hydrochara and Hydrophilus with an increased number of chromosomes (2n = 30). The number of chromosomes is increased in the subfamily Cylominae (2n = 24–30) and in all subclades of the subfamily Sphaeridiinae (2n = 22–32). We summarize protocols for obtaining chromosome slides used for this study and provide step-by-step guidelines to facilitate future cytogenetic studies.

Excellent wound dressing is essential for effective wound repair and regeneration. This chapter aims to evaluate the effectiveness of bacterial cellulose (BC) and type I collagen (COL) scaffolds conjugated with resveratrol (RSV) for wound management. BC and COL are biodegradable and renewable attractive polymers for medical applications which has a strong affinity for materials containing hydroxyl groups, meanwhile RSV has a 4′-hydroxyl group and exhibits good biocompatibility and no cytotoxicity. The results demonstrated that RSV was effectively released from the BC and COL scaffolds in vitro, and immunofluorescence staining showed that both scaffolds were highly biocompatible and regenerated epithelia. Additionally, Masson’s trichrome staining showed that the both scaffolds preserved the normal collagen-bundling pattern and induced re-epithelialization in defective rat epidermis. These results indicate that RSV-conjugated BC or COL scaffold created a biocompatible environment for stem cell attachment and growth and promoted epithelial regeneration during wound healing.

Taiwanese species of the genus Laccobius Erichson, 1837 (Coleoptera: Hydrophilidae) are reviewed based on newly collected material and published records. Five species classified in two subgenera are recorded for the region, including L. (Glyptolaccobius) politus Gentili, 1979, L. (Microlaccobius) formosus Gentili, 1979, L. (M.) hammondi Gentili, 1984, L. (M.) roseiceps Régimbart, 1903 and a new species from central and southern Taiwan: L. (M.) hoi. sp.nov. Laccobius philipinus Gentili, 2005 is excluded from Taiwanese fauna. We failed to re-collect Laccobius fragilis Nakane, 1966 despite sampling the area from which it was recorded, and its occurrence in Taiwan hence needs re-confirmation. Distribution data of all Taiwanese species is summarized, and a key of Taiwanese Laccobius and photographs of all species are provided.

Improvement in outcomes of children with acute myeloid leukemia (AML) is attributed to several refinements in clinical management. We evaluated treatment outcomes of Taiwanese pediatric AML patients in the past 20 years. Overall, 860 de novo AML patients aged 0–18 years and registered in the Childhood Cancer Foundation of R.O.C during January 1996–December 2019 were included. Survival analysis was performed to identify factors that improved treatment outcomes. Regardless of treatment modalities used, patients during 2008–2019 had better 5-year event-free survival (EFS) and overall survival (OS) rates than patients during 1996–2007. For patients received the TPOG-AML-97A treatment, only 5-year OS rates were significantly different between patients diagnosed before and after 2008. Patients with RUNX1–RUNX1T1 had similar relapse-free survival rates, but 5-year OS rates were better during 2008–2019. However, the survival of patients who received hematopoietic stem-cell transplantations (HSCT) did not differ significantly before and after 2008. For patients without relapse, the 5-year OS improved during 2008–2019. Non-relapse mortality decreased annually, and cumulative relapse rates were similar. In conclusion, 5-year EFS and OS rates improved during 2008–2019, though intensities of chemotherapy treatments were similar before and after 2008. Non-relapse mortality decreased gradually. Further treatment strategies including more intensive chemotherapy, novel agents’ use, identification of high-risk patients using genotyping and minimal residual disease, early intervention of HSCT, and antibiotic prophylaxis can be considered for future clinical protocol designs in Taiwan.

The image quality of reflective optical systems is influenced strongly when the position of each mirror changed compared to the theoretical design state. Since multiple degrees of freedom in reflective optical system and the interaction between each mirror coupled, which makes it difficult to separate the misalignment of each mirror accurately. By now, vector wave-front aberration theory has been used to computer-aided alignment of two-mirror and three-mirror optical systems widely, however, due to actual engineering demands, optical systems with more than three mirrors have been designed, which greatly increases the difficulty of installation and alignment. At present, there are still few researches on this aspect. Based on vector wave aberration theory, the aberration shift vector of each element in four-mirror optical systems with off-axis field is derived by using paraxial ray trace equation of the optical axis ray and the principle ray, then the misalignment model of the four-mirror optical systems with shifted field is established in detail. The model can accurately calculate the misalignment of optical elements, which greatly promotes the high-precision alignment of complex reflective optical systems. And the perturbed off-axis four-mirror telescope can be perfectly aligned in terms of the vector aberration theory. This greatly facilitates the optical design technology of complex reflective optical systems in some way.

Reflective optical systems have many advantages such as no chromatic aberration, wide detection band range, suitable for large aperture, light weight and compact structure. More and more two-mirror and three-mirror optical systems have been applied widely, which greatly promotes the development of space optical detection technology. With the continuous development of optical design, in order to increase the field of view, eliminate stray light and compact systems structure, some off-axis four mirror optical systems have been designed. Based on the vector wave-front aberration theory of reflective optical systems, a design method of off-axis four-mirror optical system is proposed in this paper. This method is more intuitive in aberration optimization and can greatly improve the design efficiency of optical system. At last, by using of the optical design software CODE V, a four-mirror optical system with the off-axis field of view is designed.

Enterovirus uncoating receptors bind at the surface depression ("canyon") that encircles each capsid vertex causing the release of a host-derived lipid called "pocket factor" that is buried in a hydrophobic pocket formed by the major viral capsid protein, VP1. Coxsackievirus and adenovirus receptor (CAR) is a universal uncoating receptor of group B coxsackieviruses (CVB). Here, we present five high-resolution cryoEM structures of CVB representing different stages of virus infection. Structural comparisons show that the CAR penetrates deeper into the canyon than other uncoating receptors, leading to a cascade of events: collapse of the VP1 hydrophobic pocket, high-efficiency release of the pocket factor and viral uncoating and genome release under neutral pH, as compared with low pH. Furthermore, we identified a potent therapeutic antibody that can neutralize viral infection by interfering with virion-CAR interactions, destabilizing the capsid and inducing virion disruption. Together, these results define the structural basis of CVB cell entry and antibody neutralization.

5-year overall survival rates have surpassed 90% for childhood acute lymphocytic leukaemia, but survivors are at risk for permanent health sequelae. Although event-free survival appropriately represents the outcome for cancers with poor overall survival, this metric is inadequate when cure rates are high but challenged by serious, persistent complications. Accordingly, a group of experts in paediatric haematology-oncology, representative of 17 international acute lymphocytic leukaemia study groups, launched an initiative to construct a measure, designated severe toxicity-free survival (STFS), to quantify the occurrence of physician-prioritised toxicities to be integrated with standard cancer outcome reporting. Five generic inclusion criteria (not present before cancer diagnosis, symptomatic, objectifiable, of unacceptable severity, permanent, or requiring unacceptable treatments) were used to assess 855 health conditions, which resulted in inclusion of 21 severe toxicities. Consensus definitions were reached through a modified Delphi process supplemented by two additional plenary meetings. The 21 severe toxicities include severe adverse health conditions that substantially affect activities of daily living and are refractory to therapy (eg, refractory seizures), are without therapeutic options (eg, blindness), or require substantially invasive treatment (eg, cardiac transplantation). Incorporation of STFS assessment into clinical trials has the potential to improve and diversify treatment strategies, focusing not only on traditional outcome events and overall survival but also the frequencies of the most severe toxicities. The two major aims of this Review were to: prioritise and define unacceptable long-term toxicity for patients with childhood acute lymphocytic leukaemia, and define how these toxicities should be combined into a composite quantity to be integrated with other reported outcomes. Although STFS quantifies the clinically unacceptable health tradeoff for cure using childhood acute lymphocytic leukaemia as a model disease, the prioritised severe toxicities are based on generic considerations of relevance to any other cancer diagnosis and age group.

Publisher Copyright: © 2021 Lippincott Williams and Wilkins. All rights reserved. Asparaginase-associated pancreatitis (AAP) frequently affects children treated for acute lymphoblastic leukemia (ALL) causing severe acute and persisting complications. Known risk factors such as asparaginase dosing, older age and single nucleotide polymorphisms (SNPs) have insufficient odds ratios to allow personalized asparaginase therapy. In this study, we explored machine learning strategies for prediction of individual AAP risk. We integrated information on age, sex, and SNPs based on Illumina Omni2.5exome-8 arrays of patients with childhood ALL (N=1564, 244 with AAP aged 1.0 to 17.9 y) from 10 international ALL consortia into machine learning models including regression, random forest, AdaBoost and artificial neural networks. A model with only age and sex had area under the receiver operating characteristic curve (ROC-AUC) of 0.62. Inclusion of 6 pancreatitis candidate gene SNPs or 4 validated pancreatitis SNPs boosted ROC-AUC somewhat (0.67) while 30 SNPs, identified through our AAP genome-wide association study cohort, boosted performance (0.80). Most predictive features included rs10273639 (PRSS1-PRSS2), rs10436957 (CTRC), rs13228878 (PRSS1/PRSS2), rs1505495 (GALNTL6), rs4655107 (EPHB2) and age (1 to 7 y). Second AAP following asparaginase re-exposure was predicted with ROC-AUC: 0.65. The machine learning models assist individual-level risk assessment of AAP for future prevention trials, and may legitimize asparaginase re-exposure when AAP risk is predicted to be low.