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There is currently no effective treatment against Alzheimer's disease (AD), although many strategies have been applied to reduce beta-amyloid (Aβ) levels. Here, we investigated 2,4-diacetylphloroglucinol (DAPG) effects on Aβ levels and mechanisms of action. DAPG was the most effective phloroglucinol derivative for reducing Aβ levels, without being toxic, in various models including HEK293 cells overexpressing Swedish mutant amyloid precursor protein (APP) (293sw), primary astrocytes isolated from APPsw/PS1dE9 transgenic mice, and after intrahippocampal injection of DAPG in APPsw/PS1dE9 transgenic mice. DAPG-mediated Aβ reduction was associated with increased soluble APPα (sAPPα) levels mediated by a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) but not ADAM17. ADAM10 inhibition in DAPG-treated cells prevented the effects on sAPPα but only partly on intracellular and secreted Aβ. To identify regulators of sAPPα and Aβ secretion, various inhibitors of intracellular trafficking were administered with DAPG. Brefeldin A (BFA) reversed DAPG-mediated changes in Aβ secretion in 293sw cells, whereas golgicide A (GCA) and BFA were effective in primary astrocytes, indicating a cell type-specific regulation of the trafficking. Moreover, GCA or BFA effects on sAPPα, but not Aβ, levels in primary astrocytes resembled those of ADAM10 inhibition, indicating at least partly independent trafficking pathways for sAPPα and Aβ. In conclusion, DAPG might be a promising drug candidate against AD regulating ADAM10 and intracellular trafficking, but optimizing DAPG ability to cross the BBB will be needed., Competing Interests: The authors declare no conflicts of interest.

Several detectors have been developed to measure radiation doses during radiotherapy. However, most detectors are not flexible. Consequently, the airgaps between the patient surface and detector could reduce the measurement accuracy. Thus, this study proposes a dose measurement system based on a flexible copper indium gallium selenide (CIGS) solar cell. Our system comprises a customized CIGS solar cell (with a size 10 × 10 cm2 and thickness 0.33 mm), voltage amplifier, data acquisition module, and laptop with in-house software. In the study, the dosimetric characteristics, such as dose linearity, dose rate independence, energy independence, and field size output, of the dose measurement system in therapeutic X-ray radiation were quantified. For dose linearity, the slope of the linear fitted curve and the R-square value were 1.00 and 0.9999, respectively. The differences in the measured signals according to changes in the dose rates and photon energies were <2% and <3%, respectively. The field size output measured using our system exhibited a substantial increase as the field size increased, contrary to that measured using the ion chamber/film. Our findings demonstrate that our system has good dosimetric characteristics as a flexible in vivo dosimeter. Furthermore, the size and shape of the solar cell can be easily customized, which is an advantage over other flexible dosimeters based on an a-Si solar cell.

Paraquat is a polar herbicide protecting plant products against invasive species, it requires careful manipulation and restricted usage because of its harmful potentials. Exposure to paraquat triggers oxidative damage in dopaminergic neurons and subsequently causes a behavioral defect in vivo. Thereby, persistent exposure to paraquat is known to increase Parkinson's disease risk by dysregulating dopaminergic systems in humans. Therefore, most studies have focused on the dopaminergic systems to elucidate the neurotoxicological mechanism of paraquat poisoning, and more comprehensive neurochemistry including histaminergic, serotonergic, cholinergic, and GABAergic systems has remained unclear. Therefore, in this study, we investigated the toxicological potential of paraquat poisoning using a variety of approaches such as toxicokinetic profiles, behavioral effects, neural activity, and broad-spectrum neurochemistry in zebrafish larvae after short-term exposure to paraquat and we performed the molecular modeling approach. Our results showed that paraquat was slowly absorbed in the brain of zebrafish after oral administration of paraquat. In addition, paraquat toxicity resulted in behavioral impairments, namely, reduced motor activity and led to abnormal neural activities in zebrafish larvae. This locomotor deficit came with a dysregulation of dopamine synthesis induced by the inhibition of tyrosine hydroxylase activity, which was also indirectly confirmed by molecular modeling studies. Furthermore, short-term exposure to paraquat also caused simultaneous dysregulation of other neurochemistry including cholinergic and serotonergic systems in zebrafish larvae. The present study suggests that this neurotoxicological profiling could be a useful tool for understanding the brain neurochemistry of neurotoxic agents that might be a potential risk to human and environmental health., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study is to investigate the optimal treatment option for synchronous bilateral breast cancer (SBBC) by comparing dosimetric and radiobiological parameters of intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) plans using single and dual isocenters. Twenty patients with SBBC without lymph node involvement were selected retrospectively. Four treatment plans were generated for each patient using the Eclipse treatment planning system (Varian Medical System, Palo Alto, CA, USA) following two delivery techniques with two isocenter conditions-IMRT using a single isocenter (IMRT&#95;Iso1), VMAT using a single isocenter (VMAT&#95;Iso1), IMRT using dual isocenters (IMRT&#95;Iso2), and VMAT using dual isocenters (VMAT&#95;Iso2). A dose of 42.56 Gy in 16 fractions was prescribed for the planning target volume (PTV). All plans were calculated using the Acuros XB algorithm and a photon optimizer for a 6-MV beam of a Vital Beam linear accelerator. PTV-related dosimetric parameters were analyzed. Further, the homogeneity index, conformity index, and conformation number were computed to evaluate plan quality. Dosimetric parameters were also measured for the organs at risk (OARs). In addition, the equivalent uniform dose corresponding to an equivalent dose related to a reference of 2 Gy per fraction, the tumor control probability, and the normal tissue complication probability were calculated based on the dose-volume histogram to investigate the radiobiological impact on PTV and OARs. IMRT&#95;Iso1 exhibited similar target coverage and a certain degree of dosimetric improvement in OAR sparing compared to the other techniques. It also exhibited some radiobiological improvement, albeit insignificant. Although IMRT&#95;Iso1 significantly increased monitor unit compared to VMAT&#95;Iso1, which is the best option in terms of delivery efficiency, there was only a 22% increase in delivery time. Therefore, in conclusion, IMRT&#95;Iso1, the complete treatment of which can be completed using a single setup, is the most effective method for treating SBBC., (© 2022 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

CD4 + T cells are central to long-term immunity against viruses through the functions of T helper 1 (T H 1) and T follicular helper (T FH ) cell subsets. To better understand the role of these subsets in coronavirus disease 2019 (COVID-19) immunity, we conducted a longitudinal study of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific CD4 + T cell and antibody responses in convalescent individuals who seroconverted during the first wave of the pandemic in Boston, MA, USA, across a range of COVID-19 disease severities. Analyses of spike (S) and nucleocapsid (N) epitope-specific CD4 + T cells using peptide and major histocompatibility complex class II (pMHCII) tetramers demonstrated expanded populations of T cells recognizing the different SARS-CoV-2 epitopes in most individuals compared with prepandemic controls. Individuals who experienced a milder disease course not requiring hospitalization had a greater percentage of circulating T FH (cT FH ) and T H 1 cells among SARS-CoV-2-specific cells. Analysis of SARS-CoV-2-specific CD4 + T cells responses in a subset of individuals with sustained anti-S antibody responses after viral clearance also revealed an increased proportion of memory cT FH cells. Our findings indicate that efficient early disease control also predicts favorable long-term adaptive immunity.

Purpose: Thermoplastic masks keep patients in an appropriate position to ensure accurate radiation delivery. For a thermoplastic mask to maintain clinical efficacy, the mask should wrap the patient's surface properly and provide uniform pressure to all areas. However, to our best knowledge, no explicit method for achieving such a goal currently exists. Therefore, in this study, we intended to develop a real-time thermoplastic mask compression force (TMCF) monitoring system to measure compression force quantitatively. A prototype system was fabricated, and the feasibility of the proposed method was evaluated. Methods: The real-time TMCF monitoring system basically consists of four force sensor units, a microcontroller board (Arduino Bluno Mega 2560), a control PC, and an in-house software program. To evaluate the reproducibility of the TMCF monitoring system, both a reproducibility test using a micrometer and a setup reproducibility test using a head phantom were performed. Additionally, the reproducibility tests of mask setup and motion detection tests were carried out with a cohort of six volunteers. Results: The system provided stable pressure readings in all 10 trials during the sensor unit reproducibility test. The largest standard deviation (SD) among trials was about 36 gf/cm 2 (∼2.4% of the full-scale range). For five repeated mask setups on the phantom, the compression force variation of the mask was less than 39 gf/cm 2 (2.6% of the full-scale range). We were successful in making masks together with the monitoring system connected and demonstrated feasible utilization of the system. Compression force variations were observed among the volunteers and according to the location of the sensor (among forehead, both cheekbones, and chin). The TMCF monitoring system provided the information in real time on whether the mask was properly pressing the human subject as an immobilization tool. Conclusion: With the developed system, it is possible to monitor the effectiveness of the mask in real time by continuously measuring the compression force between the mask and patient during the treatment. The graphical user interface (GUI) of the monitoring system developed provides a warning signal when the compression force of the mask is insufficient. Although the number of volunteers participated in the study was small, the obtained preliminary results suggest that the system could ostensibly improve the setup accuracy of a thermoplastic mask., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kim, Cho, Shin, Shin and Kim.)

Unleashing the immune system to fight cancer has been a major breakthrough in cancer therapeutics since 2014 when anti-PD-1 antibodies (pembrolizumab and nivolumab) were approved for patients with metastatic melanoma. Therapeutic indications have rapidly expanded for many types of advanced cancer, including lung cancer. A variety of antibodies targeting the PD-1/PD-L1 checkpoint are contributing to this paradigm shift. The field now confronts two salient challenges: first, to improve the therapeutic outcome given the low response rate across the histologies; second, to identify biomarkers for improved patient selection. Pre-clinical and clinical studies are underway to evaluate combinatorial treatments to improve the therapeutic outcome paired with correlative studies to identify the factors associated with response and resistance. One of the emerging strategies is to combine epigenetic modifiers with immune checkpoint blockade (ICB) based on the evidence that targeting epigenetic elements can enhance anti-tumor immunity by reshaping the tumor microenvironment (TME). We will briefly review pleotropic biological functions of enhancer of zeste homolog 2 (EZH2), the enzymatic subunit of polycomb repressive complex 2 (PRC2), clinical developments of oral EZH2 inhibitors, and potentially promising approaches to combine EZH2 inhibitors and PD-1 blockade for patients with advanced solid tumors, focusing on lung cancer., (Copyright © 2022. Published by Elsevier Inc.)

Objective: A distal navigation of a large bore aspiration catheter during mechanical thrombectomy (MT) is important. However, delivering a large bore aspiration catheter is difficult to a tortuous or atherosclerotic artery. We report the experience of anchoring with balloon guide catheter (BGC) and stent retriever to facilitate the passage of an aspiration catheter in MT., Methods: When navigating an aspiration catheter failed with a conventional co-axial microcatheter delivery, an anchoring technique was used. Two types of anchoring technique were applied to facilitate distal navigation of a large bore aspiration catheter during MT. First, a passage of aspiration catheter was attempted with a proximal BGC anchoring technique. If this technique also failed, another anchoring technique with distal stent retriever was tried. Consecutive patients who underwent MT with an anchoring technique were identified. Details of procedure, radiologic outcomes, and safety variables were evaluated., Results: A total of 67 patients underwent MT with an anchoring technique. Initial trial of aspiration catheter passage with proximal BGC anchoring technique was successful for 35 patients (52.2%) and the second trial with distal stent retriever anchoring was successful for 32 patients (47.8%). Overall, navigation of a large bore aspiration catheter was successful for all patients (100%) without any procedure related complications., Conclusion: Our study showed the usefulness of anchoring technique with proximal BGC and distal stent retriever during MT, especially in those with an unfavorable anatomical structure. This technique could be an alternative option for delivering an of aspiration catheter to a distal location.

Diagnosis of coronavirus disease (COVID-19) is important because of the emergence and global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Real-time polymerase chain reaction (PCR) is widely used to diagnose COVID-19, but it is time-consuming and requires sending samples to test centers. Thus, the need to detect antigens for rapid on-site diagnosis rather than PCR is increasing. We quantified the nucleocapsid (N) protein in SARS-CoV-2 using an electro-immunosorbent assay (El-ISA) and a multichannel impedance analyzer with a 96-interdigitated microelectrode sensor (ToAD). The El-ISA measures impedance signals from residual detection antibodies after sandwich assays and thus offers highly specific, label-free detection of the N protein with low cross-reactivity. The ToAD sensor enables the real-time electrochemical detection of multiple samples in conventional 96-well plates. The limit of detection for the N protein was 0.1 ng/mL with a detection range up to 10 ng/mL. This system did not detect signals for the S protein. While this study focused on detecting the N protein in SARS-CoV-2, our system can also be widely applicable to detecting various biomolecules involved in antigen-antibody interactions.

Overactive bladder (OAB) is a syndrome causing a sudden and unstoppable need to urinate with significant global prevalence. Several drugs are used to treat OAB; however, they have various side effects. Therefore, new treatment options for OAB are required. A series of novel 5-oxo- N -phenyl-1-thioxo-4,5-dihydro-1 H -thiazolo[3,4- a ]quinazoline-3-carboxamide derivatives were synthesized and evaluated for their large-conductance voltage- and Ca 2+ -activated K + channel activation through a cell-based fluorescence assay and electrophysiological recordings. Several compounds, including a 7-bromo substituent on the heterocyclic system, showed increased channel currents. Among the derivatives, compound 12h exhibited potent in vitro activity with a half-maximal effective concentration (EC 50 ) of 2.89 μM, good oral pharmacokinetic properties (area under the curve and half-life), and in vivo efficacy in a spontaneously hypertensive rat model., Competing Interests: The authors declare no competing financial interest., (© 2022 American Chemical Society.)

To date, for the diagnosis of dentofacial dysmorphosis, we have relied almost entirely on reference points, planes, and angles. This is time consuming, and it is also greatly influenced by the skill level of the practitioner. To solve this problem, we wanted to know if deep neural networks could predict postoperative results of orthognathic surgery without relying on reference points, planes, and angles. We use three-dimensional point cloud data of the skull of 269 patients. The proposed method has two main stages for prediction. In step 1, the skull is divided into six parts through the segmentation network. In step 2, three-dimensional transformation parameters are predicted through the alignment network. The ground truth values of transformation parameters are calculated through the iterative closest points (ICP), which align the preoperative part of skull to the corresponding postoperative part of skull. We compare pointnet, pointnet++ and pointconv for the feature extractor of the alignment network. Moreover, we design a new loss function, which considers the distance error of transformed points for a better accuracy. The accuracy, mean intersection over union (mIoU), and dice coefficient (DC) of the first segmentation network, which divides the upper and lower part of skull, are 0.9998, 0.9994, and 0.9998, respectively. For the second segmentation network, which divides the lower part of skull into 5 parts, they were 0.9949, 0.9900, 0.9949, respectively. The mean absolute error of transverse, anterior-posterior, and vertical distance of part 2 (maxilla) are 0.765 mm, 1.455 mm, and 1.392 mm, respectively. For part 3 (mandible), they were 1.069 mm, 1.831 mm, and 1.375 mm, respectively, and for part 4 (chin), they were 1.913 mm, 2.340 mm, and 1.257 mm, respectively. From this study, postoperative results can now be easily predicted by simply entering the point cloud data of computed tomography.

Musculoskeletal pains seem to be the most prevalent among occupational diseases in older female farmers. This study analyzes the relationships between exposure to ergonomic or environmental hazards, sleep-related problems, wellbeing, and musculoskeletal pains in older female farmers. In this study, older farmer means a farmer aged ≥60, and 2005 older female farmers were selected. A structural equation model (SEM) was used to investigate the relationships. In the results of SEM, musculoskeletal pains were more affected by the level of wellbeing (standardized path coefficient = -0.149) than the level of sleep-related problems (standardized path coefficient = 0.131) or the exposure level of ergonomic hazards (standardized path coefficient = 0.086). Among the ergonomic risk factors felt by elderly female farmers, the influence level of "awkward posture" (0.735), "repetitive motion" (0.718), or "standing posture" (0.693) was greater than that of "manual material handling" (0.661). "Vibration" (0.786) and "noise" (0.683) were influential variables of environmental hazards. In addition, "upper limb pain" (0.796) and "lower limb pain" (0.751) variables were more influential variables of musculoskeletal pains than the "backache" (0.472) variable. This study shows that strategies to improve wellbeing or sleep problems are important to alleviate or prevent musculoskeletal pains among older female farmers.

Electrical and optical characteristics of InGaN-based green micro-light-emitting diodes (µLEDs) with different active areas are investigated; results are as follows. Reverse and forward leakage currents of µLED increase as emission area is reduced owing to the non-radiative recombination process at the sidewall defects; this is more prominent in smaller µLED because of larger surface-to-volume ratio. Leakage currents of µLEDs deteriorate the carrier injection to light-emitting quantum wells, thereby degrading their external quantum efficiency. Reverse leakage current originate primarily from sidewall edges of the smallest device. Therefore, aggressive suppression of sidewall defects of µLEDs is essential for low-power and downscaled µLEDs.

One of the oldest mechanisms of immune defense against pathogens is through detection of foreign DNA. Since human DNA is compartmentalized into the nucleus, its presence in the cytosol heralds a potential threat. The cGAS-STING pathway is one of the most important cytosolic DNA sensing pathways and leads to interferon signaling, inflammasome activation, autophagy, and cell death. While STING signaling is protective at physiologic levels, chronic activation of this pathway can instead drive autoinflammation and autoimmunity. Here we discuss several monogenic disorders of the STING pathway that highlight its impact on both innate and adaptive immunity in the progressive loss of tolerance. The potential relevance of STING signaling in systemic lupus erythematosus is then discussed with a focus on future avenues for monitoring and targeting this pathway., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wobma, Shin, Chou and Dedeoğlu.)

Ras-related protein Ral-A (RalA)-binding protein 1 (RalBP1, also known as Ral-interacting protein of 76 kDa (RLIP76) or Ral-interacting protein 1 (RLIP1 or RIP1)) is involved in the efflux of 4-hydroxynonenal (4-HNE, an end product of lipid peroxidation), as well as mitochondrial fission. In the present study, we found that 2-cyano-3,12-dioxo-oleana-1,9(11)-dien-28-oic acid methyl ester (CDDO-Me) attenuated CA1 neuronal death and aberrant mitochondrial elongations in these neurons coupled with enhanced RalBP1 expression and reduced 4-HNE levels following status epilepticus (SE). RalBP1 knockdown did not affect mitochondrial dynamics and CA1 neuronal death under physiological and post-SE conditions. Following SE, however, cotreatment of RalBP1 siRNA diminished the effect of CDDO-Me on 4-HNE levels, mitochondrial hyperfusion in CA1 neurons, and CA1 neuronal death. These findings indicate that CDDO-Me may ameliorate CA1 neuronal death by facilitating RalBP1-mediated 4-HNE efflux and mitochondrial fission following SE. Therefore, our findings suggest that increased RalBP1 expression/activity may be one of the considerable targets to protect neurons from SE.

In this study, we evaluated changes in the masseter and lateral pterygoid muscles in the prognathic mandible group after a mandibular setback by comparing the volume-to-length ratios. Preoperative and postoperative 1-year computed tomography was used to calculate the volume-to-length ratio of the lateral pterygoid and masseter muscle in 60 Korean individuals. Three-dimensional images were reconstructed, the results of which showed no significant differences in the volume-to-length ratios of the masseter and lateral pterygoid muscles after a mandibular setback (p > 0.05). This result was found for both vertical ramus osteotomy and sagittal split ramus osteotomy, and for both males and females. No significant differences in the volume-to-length ratio of the masseter and lateral pterygoid muscles were found up to 1 year after a mandibular setback. Therefore, this study can contribute to the prediction of soft-tissue profiles after mandibular setback.

External lumbar drain placement has been shown to be an efficacious and safe approach to managing various forms of intracranial hypertension in adult patients and children. The use of ultrasound guidance for lumbar punctures in young patients has been described however, but the modality is not routinely used for the placement of tunneled lumbar drains. In this report, two cases are presented that detail experience using ultrasound guidance for tunneled lumbar drains in children., (© 2021 Wiley Periodicals LLC.)

The COVID-19 pandemic is a global health threat. Smoking and smoking-related lung diseases are risk factors for severe COVID-19 infection. This study investigated whether low-dose computed tomography (LDCT) scan results affected the success of 1-year smoking cessation. The Gyeonggi Southern Smoking Support Center performed the residential smoking cessation program from January to December 2018. During the program, LDCT was performed on 292 participants; 6 months later, follow-up via telephone or visit was conducted. Among the 179 participants who succeeded in smoking cessation for 6 months, telephone follow-up was conducted to determine whether there was a 12-month continuous smoking cessation. In order to evaluate the association between LDCT results and 12-month continuous abstinence rate (CAR), logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI). The CARs at 6 and 12 months were 61.3% and 31.5%, respectively. Indeterminate or suspicious malignant lung nodules were associated with a higher 12-month CAR (OR, 3.02; 95% CI, 1.15-7.98), whereas psychiatric history was associated with a lower 12-month CAR (OR, 0.06; 95% CI, 0.03-0.15). These results suggest that abnormal lung screening results may encourage smokers to quit smoking.

Camphor tree ( Cinnamomum camphora ) is an ornamental plant that has been cultivated for a long time to obtain wood or camphor. Furthermore, its essential oil can be used as an alternative medicine and is an important source of perfume. Camphor obtained from camphor trees has long been used as a treatment for various symptoms such as inflammation, infection, congestion, muscle pain, and irritation in various regions. The purpose of this literature review is to provide knowledge of the well-established, wide, and extensive applications of camphor both in traditional and modern applications. Despite many studies focused on the essential oil of the camphor tree, there is a lack of systematic studies of its extraction or separation. Besides, various components of camphor are not fully understood, and further research is needed on the medicinal effects of individual components of C. camphor . The genus Cinnamomum has crucial economic value and theoretical significance. However, further systematic reviews and investigative studies based on existing research are needed to promote the modernization process of traditional applications of camphor. For proper use of the essential oil of C. camphora , it is imperative to consider its possible effects on humans and the environment.

Clasmatodendrosis is one of the irreversible astroglial degeneration, which is involved in seizure duration and its progression in the epileptic hippocampus. Although sustained heat shock protein 25 (HSP25) induction leads to this autophagic astroglial death, dysregulation of mitochondrial dynamics (aberrant mitochondrial elongation) is also involved in the pathogenesis in clasmatodendrosis. However, the underlying molecular mechanisms of accumulation of elongated mitochondria in clasmatodendritic astrocytes are elusive. In the present study, we found that clasmatodendritic astrocytes showed up-regulations of HSP25 expression, AKT serine (S) 473 and dynamin-related protein 1 (DRP1) S637 phosphorylations in the hippocampus of chronic epilepsy rats. 2-Cyano-3,12-dioxo-oleana-1,9(11)-dien-28-oic acid methyl ester (CDDO-Me; bardoxolone methyl or RTA 402) abrogated abnormal mitochondrial elongation by reducing HSP25 upregulation, AKT S473- and DRP1 S637 phosphorylations. Furthermore, HSP25 siRNA and 3-chloroacetyl-indole (3CAI, an AKT inhibitor) abolished AKT-DRP1-mediated mitochondrial elongation and attenuated clasmatodendrosis in CA1 astrocytes. These findings indicate that HSP25-AKT-mediated DRP1 S637 hyper-phosphorylation may lead to aberrant mitochondrial elongation, which may result in autophagic astroglial degeneration. Therefore, our findings suggest that the dysregulation of HSP25-AKT-DRP1-mediated mitochondrial dynamics may play an important role in clasmatodendrosis, which would have implications for the development of novel therapies against various neurological diseases related to astroglial degeneration.

P2X7 receptor (P2X7R) regulates inducible nitric oxide synthase (iNOS) expression/activity in response to various harmful insults. Since P2X7R deletion paradoxically decreases the basal glutathione (GSH) level in the mouse hippocampus, it is likely that P2X7R may increase the demand for GSH for the maintenance of the intracellular redox state or affect other antioxidant defense systems. Therefore, the present study was designed to elucidate whether P2X7R affects nuclear factor-erythroid 2-related factor 2 (Nrf2) activity/expression and GSH synthesis under nitrosative stress in response to lipopolysaccharide (LPS)-induced neuroinflammation. In the present study, P2X7R deletion attenuated iNOS upregulation and Nrf2 degradation induced by LPS. Compatible with iNOS induction, P2X7R deletion decreased S -nitrosylated (SNO)-cysteine production under physiological and post-LPS treated conditions. P2X7R deletion also ameliorated the decreases in GSH, glutathione synthetase, GS and ASCT2 levels concomitant with the reduced S -nitrosylations of GS and ASCT2 following LPS treatment. Furthermore, LPS upregulated cystine:glutamate transporter (xCT) and glutaminase in P2X7R +/+ mice, which were abrogated by P2X7R deletion. LPS did not affect GCLC level in both P2X7R +/+ and P2X7R -/- mice. Therefore, our findings indicate that P2X7R may augment LPS-induced neuroinflammation by leading to Nrf2 degradation, aberrant glutamate-glutamine cycle and impaired cystine/cysteine uptake, which would inhibit GSH biosynthesis. Therefore, we suggest that the targeting of P2X7R, which would exert nitrosative stress with iNOS in a positive feedback manner, may be one of the important therapeutic strategies of nitrosative stress under pathophysiological conditions.

Glutathione peroxidase-1 (GPx1) catalyze the reduction of H 2 O 2 by using glutathione (GSH) as a cofactor. However, the profiles of altered GPx1 expression in response to status epilepticus (SE) have not been fully explored. In the present study, GPx1 expression was transiently decreased in dentate granule cells, while it was temporarily enhanced and subsequently reduced in CA1 neurons following SE. GPx1 expression was also transiently declined in CA1 astrocytes (within the stratum radiatum) following SE. However, it was elevated in reactive CA1 astrocytes, but not in clasmatodendritic CA1 astrocytes, in chronic epilepsy rats. Under physiological condition, L-buthionine sulfoximine (BSO, an inducer of GSH depletion) increased GPx1 expression in CA1 neurons but decreased it in CA1 astrocytes. However, N-acetylcysteine (NAC, an inducer of GSH synthesis) did not influence GPx1 expression in these cell populations. Following SE, BSO aggravated CA1 neuronal death, concomitant with reduced GPx1 expression. Further. BSO also lowered GPx1 expression in CA1 astrocytes. NAC effectively prevented neuronal death and GPx1 downregulation in CA1 neurons, and restored GPx1 expression to the control level in CA1 astrocytes. In chronic epilepsy rats, BSO reduced GPx1 intensity and exacerbated clasmatodendritic degeneration in CA1 astrocytes. In contrast, NAC restored GPx1 expression in clasmatodendritic astrocytes and ameliorated this autophagic astroglial death. To the best of our knowledge, our findings report, for the first time, the spatiotemporal profiles of altered GPx1 expression in the rat hippocampus following SE, and suggest GSH-mediated GPx1 regulation, which may affect SE-induced neuronal death and autophagic astroglial degeneration.

Citrus fruits undergo significant metabolic profile changes during their development process. However, limited information is available on the changes in the metabolites of Citrus unshiu during fruit development. Here, we analyzed the total phenolic content (TPC), total carotenoid content (TCC), antioxidant activity, and metabolite profiles in C. unshiu fruit flesh during different stages of fruit development and evaluated their correlations. The TPC and antioxidant activity significantly decreased during fruit development, whereas the TCC increased. The metabolite profiles, including sugars, acidic compounds, amino acids, flavonoids, limonoids, carotenoids, and volatile compounds (mono- and sesquiterpenes), in C. unshiu fruit flesh also changed significantly, and a citrus metabolomic pathway related to fruit development was proposed. Based on the data, C. unshiu fruit development was classified into three groups: Group 1 (Aug. 1), Group 2 (Aug. 31 and Sep. 14), and Group 3 (Oct. 15 and Nov. 16). Although citrus peel was not analyzed and the sensory and functional qualities during fruit development were not investigated, the results of this study will help in our understanding of the changes in chemical profile during citrus fruit development. This can provide vital information for various applications in the C. unshiu industry.

A collagen-rich tumor microenvironment (TME) is associated with worse outcomes in cancer patients and contributes to drug resistance in many cancer types. In melanoma, stiff and fibrillar collagen-abundant tissue is observed after failure of therapeutic treatments with BRAF inhibitors. Increased collagen in the TME can affect properties of the extracellular matrix (ECM), including stiffness, adhesiveness, and interaction of integrins with triple helix forming nanostructures. Decoupling these biochemical and biophysical properties of the ECM can lead to a better understanding of how each of these individual properties affect melanoma cancer behavior and drug efficacy. In addition, as drug treatment can induce cancer cell phenotypic switch, cancer cell responsiveness to the TME can be dynamically changed during therapeutic treatments. To investigate cancer cell phenotype changes and the role of the cancer TME, poly(ethylene glycol) (PEG) hydrogels functionalized with collagen mimetic peptides (CMPs) is utilized, or an interpenetrating network (IPN) of type І collagen within the PEG system to culture various melanoma cell lines in the presence or absence of Vemurafenib (PLX4032) drug treatment is prepared. Additionally, the potential of using CMP functionalized PEG hydrogels, which can provide better tunability is explored, to replace the existing invadopodia assay platform based on fluorescent gelatin., (© 2021 Wiley-VCH GmbH.)

The tumor microenvironment (TME) is a complex, dynamic battlefield for both immune cells and tumor cells. The advent of the immune checkpoint inhibitors (ICI) since 2011, such as the anti-cytotoxic T-lymphocyte associated protein (CTLA)-4 and anti-programmed cell death receptor (PD)-(L)1 antibodies, provided powerful weapons in the arsenal of cancer treatments, demonstrating unprecedented durable responses for patients with many types of advanced cancers. However, the response rate is generally low across tumor types and a substantial number of patients develop acquired resistance. These primary or acquired resistance are attributed to various immunosuppressive elements (soluble and cellular factors) and alternative immune checkpoints in the TME. Therefore, a better understanding of the TME is absolutely essential to develop therapeutic strategies to overcome resistance. Numerous clinical studies are underway using ICIs and additional agents that are tailored to the characteristics of the tumor or the TME. Some of the combination treatments are already approved by the Food and Drug Administration (FDA), such as platinum-doublet chemotherapy, tyrosine kinase inhibitor (TKI) -targeting vascular endothelial growth factor (VEGF) combined with anti-PD-(L)1 antibodies or immuno-immuno combinations (anti-CTLA-4 and anti-PD-1). In this review, we will discuss the key immunosuppressive cells, metabolites, cytokines or chemokines, and hypoxic conditions in the TME that contribute to tumor immune escape and the prospect of relevant clinical trials by targeting these elements in combination with ICIs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Park, Veena and Shin.)

Background: The association between polycystic ovary syndrome (PCOS) and the risk of herpes zoster (HZ) remains unclear. This study investigated the risk of HZ in women with PCOS. Methods: This study used data from the Longitudinal Generation Tracking Database (LGTD 2005) which contains the information of 2 million randomly selected from National Health Insurance beneficiaries. Patients who received a diagnosis of PCOS between 2000 and 2017 were included in the PCOS cohort. Patients who were not diagnosed as having PCOS were randomly selected from the LGTD 2005 and included in the control cohort. Patients who were aged <20 years and had a history of HZ before the index date were excluded. Patients who were in both the cohorts were matched at a ratio of 1:1 through propensity score matching based on age, comorbidities, and medication. The primary outcome was the diagnosis of HZ. Results: A total of 20,142 patients were included in each case and control cohorts. The incidence rates of HZ in the PCOS and control cohorts were 3.92 and 3.17 per 1000 person-years, respectively. The PCOS cohort had a significantly higher risk of HZ than did the control cohort (adjusted hazard ratios [aHR] = 1.26). Among the patients aged 30−39 years, those with PCOS had a significantly higher risk of HZ than did those without PCOS (aHR = 1.31). Among the patients without any comorbidities, those with PCOS had a significantly higher risk of HZ (aHR = 1.26) than did those without PCOS. Conclusion: PCOS is associated with the risk of HZ, especially in young women. The risk of HZ should be addressed while treating patients with PCOS. An HZ vaccine is recommended for these patients.

Background: Portomesenteric and portosystemic venous occlusive disease may lead to portomesenteric hypertension, variceal bleeding, ascites and hypersplenism. Data regarding endovascular reconstructive strategies in children, however, are limited., Objective: To report technical success, outcome and patency of portomesenteric and portosystemic venous reconstruction using VIABAHN VBX balloon-expandable endoprostheses in pediatric patients., Materials and Methods: Five pediatric patients (median age: 15 years, range: 4-18 years), including 3 (60%) boys and 2 (40%) girls, with portomesenteric or portosystemic venous occlusion or recurrent stenosis, underwent balloon-expandable stent graft reconstruction. Presenting symptoms included acute variceal bleeding, without (n = 2, 40%) or with (n = 1, 20%) splenomegaly, and transfusion-dependent chronic melena (n = 1, 20%). One patient was asymptomatic (n = 1, 20%). Preprocedural imaging included Doppler ultrasound and contrast-enhanced computed tomography (CT) in all patients. Initial imaging showed 4 (80%) occlusions and 1 (20%) recurrent stenosis greater than 50%. Technical aspects of the reconstructions, technical successes, clinical outcomes and adverse events were recorded. Technical success was defined as completion of stent graft reconstruction. Adverse events were categorized according to Society of Interventional Radiology criteria. Clinical success was defined as resolution of the presenting symptoms and/or prevention of portal hypertensive sequela., Results: Venous reconstruction was technically successful in all five patients. Stent graft locations included the main portal vein in 2 (40%), the superior mesenteric vein in 1 (20%), autologous Meso-Rex shunt in 1 (20%) and splenocaval shunt in 1 (20%). Six stent grafts were placed (two stent grafts placed in a single patient). Stent grafts had a median diameter of 7 mm (range: 6-10 mm) and a median length of 59 mm (range: 19-79 mm). Median fluoroscopy time was 36.6 min (range: 13.4-95.8 min) and median air kerma was 301.0 mGy (range: 218.0-1,148.2 mGy). No adverse events occurred. Median clinical follow-up was 18 months (range: 6-29 months). Median imaging follow-up was 17 months (range: 2-29 months). Clinical success was achieved in all patients and maintained during the follow-up period. One patient required follow-up intervention with superior mesenteric vein side extension with a self-expanding bare metal stent due to perigraft stenosis detected on CT 3 months after stent placement. There were no stent graft occlusions., Conclusion: Portomesenteric and portosystemic venous reconstruction using balloon-expandable stent grafts in pediatric patients was feasible and clinically successful in this preliminary experience. Additional studies are warranted., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In pediatric liver transplantation, bile duct complications occur with a greater incidence than vascular anastomotic dysfunction and represent a major source of morbidity and mortality. While surgical re-anastomosis can reduce the need for retransplantation, interventional radiology offers minimally invasive and graft-saving therapies. The combination of small patient size and prevailing Roux-en-Y biliary enteric anastomotic techniques makes endoscopic retrograde cholangiopancreatography difficult if not impossible. Expertise in percutaneous management is therefore imperative. This article describes post-surgical anatomy, pathophysiology and noninvasive imaging of biliary complications. We review percutaneous techniques, focusing heavily on biliary access and interventions for reduced liver grafts. Subsequently we review the results and adverse events of these procedures and describe conditions that masquerade as biliary obstruction., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Spinal cord stimulation (SCS) is an effective treatment for chronic neuropathic pain. However, its clinical efficacy in regard to specific types of pain has not been well studied. The primary objective of this study was to retrospectively analyze the clinical outcomes of paddle-type SCS according to the type of neuropathic pain., Methods: Seventeen patients who underwent paddle-lead SCS at our hospital were examined. Clinical outcomes were evaluated pre- and postoperatively (3 months, 1 year, and last follow-up) using the Neuropathic Pain Symptom Inventory (NPSI). The NPSI categorizes pain as superficial, deep, paroxysmal, evoked, or dysesthesia and assess the duration of the pain (pain time score). Changes in NPSI scores were compared with change in Visual analogue scale (VAS) scores., Results: After SCS, the pain time score improved by 45% (independent t-test, p=0.0002) and the deep pain score improved by 58% (independent t-test, p=0.001). Improvements in the pain time score significantly correlated with improvements in the VAS score (r=0.667, p=0.003, Spearman correlation). Additionally, the morphine milligram equivalent value was markedly lower after vs. before surgery (~49 mg, pared t-test, p=0.002). No preoperative value was associated with clinical outcome., Conclusion: The NPSI is a useful tool for evaluating the therapeutic effects of SCS. Chronic use of a paddle-type spinal cord stimulation improved the deep pain and the pain time scores.

Intravascular ultrasound (IVUS) is used as a diagnostic adjunct to angiography and has become a valuable diagnostic and interventional tool with a well-documented safety profile. The American College of Cardiology and the European Society of Cardiology have published guidelines regarding the use of IVUS in the setting of percutaneous coronary intervention. IVUS has gained popularity in the interventional radiology (IR) community in recent years; however, there are no consensus guidelines for utilization. Furthermore, IVUS remains an infrequently used modality in pediatric IR, likely because of unfamiliarity with the equipment and techniques, as well as concerns over the compatibility of these instruments with pediatric anatomy. IVUS can be safely used as a helpful and sometimes necessary tool for pediatric interventions in appropriately selected patients. The utility of IVUS for reducing both fluoroscopy time and contrast agent volume makes it particularly valuable in pediatric practice. This article presents an overview of both the rotational and phased-array IVUS types and an in-depth discussion on the most common applications of these techniques in the pediatric setting across multiple procedure categories., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The asymmetric total syntheses of (+)-5- epi -schisansphenin B and the proposed structure of (+)-15-hydroxyacora-4(14),8-diene have been accomplished from 1,3-cyclopentadione ( 10 ) in eight synthetic steps. The enantioselective palladium-catalyzed redox-relay Heck alkenylation, the intramolecular Stetter reaction, and the regioselective Tiffeneau-Demjanov-type ring expansion were the pivotal steps in these syntheses.

Objective: Mechanical thrombectomy (MT) is an effective treatment for large vessel occlusion (LVO) with a high successful recanalization (SR) rate. However, MT fails in a proportion of patients, leading to poor clinical outcomes. We analyzed the factors associated with the failure of MT., Methods: A total of 648 consecutive patients with MT were enrolled. MT failure was defined as 0,1, or 2a of modified Thrombolysis in Cerebral Infarction (mTICI) grade. Failed MTs were divided into 3 categories, reaching failure, passage failure, and recanalization failure (RF). Various factors in RF and SR groups were analyzed with 1: 1 propensity score matching., Results: Failed MT was observed in 97 patients (14.3%). Among them, 69 patients (10.2% of the entire cohort, 71.1% of the failed MT group) were included in the RF group. Propensity matching analysis with 69 patients in each group showed that the RF group had a higher rate of residual intracranial atherosclerotic stenosis (ICAS) than the SR group (30.4% vs. 14.5% P = 0.003). The rates of 4 or more passages and no change of method were significantly higher in the RF group than in the SR group (34.8% vs. 13.0%; P = 0.001 and 28.9% vs. 8.7%; P = 0.001)., Conclusion: The failure rate for all of the MT was approximately 15%, and RF accounted for more than 70% of the failed MT. RF was associated with residual ICAS. In cases with RF, even in repeated attempts for recanalization, an alteration of the thrombectomy method should be considered., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Due to the anatomical characteristics of the anterior epidural space, dorsal migration of material from herniated lumbar disc is quite rare. Also, bilateral foot drop due to unilateral dorsal migration of disc herniation is extremely rare. This report presents a case of sudden bilateral foot drop caused by the unilateral dorsal migration of material from a herniated lumbar disc., Case Description: A 51-year-old male presented with sudden onset severe leg pain with bilateral foot drop. The patient was referred to our emergency department by a local clinic. Neurological examination showed bilateral ankle and big toe dorsiflexion weakness grade 1. There was no perianal anesthesia, anal sphincter weaknesses, or voiding difficulty. Apart from essential hypertension, this patient's medical history was unremarkable. Magnetic resonance imaging showed that intervertebral disc material in the dorsal extradural space at the L3-4 level had compressed the dural sac from the left side to the center. We performed an emergency operation. The pathologic result revealed fibrous cartilaginous materials. After the operation, the leg pain was markedly resolved. At postoperative three months, the patient showed improvement of foot drop., Conclusion: We recommended emergent mass removal, which produced a favorable outcome.

Salt is one of the most important factors for fermented foods, but the effect of salt treatment time on the quality of fermented foods has rarely been studied. In this study, the effect of different salt treatment times (0, 48, and 96 h) after the start of fermentation on the quality of the soy sauce moromi extract (SSME) was investigated. As the salt treatment time was delayed, the population of Aspergillus oryzae , Lactobacillaceae , and Enterococcaecea in SSME increased, whereas the population of Staphylococcaceae and Bacillaceae decreased, leading to changes in the enzymatic activity and metabolite profiles. In particular, the contents of amino acids, peptides, volatile compounds, acidic compounds, sugars, and secondary metabolites were significantly affected by the salt treatment time, resulting in changes in the sensory quality and appearance of SSME. The correlation data showed that metabolites, bacterial population, and sensory parameters had strong positive or negative correlations with each other. Moreover, based on metabolomics analysis, the salt treatment-time-related SSME metabolomic pathway was proposed. Although further studies are needed to elucidate the salt treatment mechanism in fermented foods, our data can be useful to better understand the effect of salt treatment time on the quality of fermented foods.

Background/aims: There have been few multicenter studies on colonic polyps conducted by primary medical institutions. This study examined the detection rate of colonic polyps in primary health care institutions and the related factors while following the guidelines., Methods: The medical records of 14,029 patients who underwent colonoscopy between January-June 2020 at 40 primary medical institutions in Korea were analyzed. High-risk adenoma was defined as advanced adenoma, carcinoma, or ≥3 adenomas., Results: Most patients (71.2%) aged ≥50 years underwent re-colonoscopy within 5 years (51.3%) for diagnostic purposes (61.3%) in Korean primary medical institutions. The detection rates of colon polyps, adenoma, advanced adenoma, high-risk adenoma, and carcinoma was 59.9%, 38.9%, 5.9%, 11.4%, and 0.3% in all subjects and 59.8%, 37.5%, 8.5%, 12.9%, and 0.3% in average-risk patients, respectively. The incidences of adenoma in average-risk patients increased significantly with age (30s/40s/50s: 20.1%/29.4%/43% for adenoma, 4.4%/6.7%/10.3% for advanced adenoma, and 5.6%/9.5%/14.6% for high-risk adenoma; p<0.05). Before 50 years of age, high-risk adenoma was detected in 9.1% of patients in the first-time screening group, and the significant risk factors were being male and ≥40 years of age. The detection rate of high-risk adenoma in the normal index colonoscopy group within 5 years was 9.0%. The significant risk factors included older age, male sex, positive fecal occult blood test, stool form changes, and nonspecific symptoms (gas and indigestion)., Conclusions: More colonic adenoma studies targeting real-world clinical practice will be needed to revise the Korean guidelines for colorectal cancer screening and surveillance.

Objective: Both physical diseases such as infection and chronic pain and psychological disorders such as depression have been associated with herpes zoster (HZ) reactivation. However, the relationship between de Quervain syndrome (DQS), a painful tenosynovitis and HZ remains unclear. We investigated whether DQS increases the risk of HZ reactivation., Design: A retrospective population-based cohort study., Setting: Taiwan., Participants: We used a subset of Taiwan's National Health Insurance Research Database, the Longitudinal Health Insurance Database which contains the registration files and original claims data of 1 million randomly selected individuals from the National Health Insurance programme. The case group in this study comprised patients newly diagnosed with DQS between 2000 and 2012. Individuals without DQS comprised the control group. Cases and controls were 1:1 matched by age, sex and index year (defined as the year of DQS diagnosis)., Results: Approximately 55% of the participants were ≤49 years. Most participants were women (77%). The incidence rate of HZ in the DQS group was 8.39 per 1000 person years. After adjustments for age, sex and comorbidities, patients with DQS had a 1.30 times higher risk of HZ reactivation than the control group. Stratification analysis revealed taht DQS increases the HZ risk in individuals ≤64 years, women, and patients without comorbidities., Conclusion: DQS is associated with an increased risk of HZ. Clinicians should be aware of this risk when dealing with patients with DQS, particularly in young adults., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: This study aimed to conduct a job analysis of nurse carecoordinators and to identify the frequency, importance and difficulty of each task of their job., Methods: A committee for developing a curriculum (DACUM) was formed and members of the committee defined nurse care coordinators' jobs and enumerated the duties, tasks and task elements by applying the DACUM technique. Then nurse care coordinators enrolled in the pilot project evaluated the frequency, importance and difficulty of each task., Results: From the job descriptions of nurse care coordinators, we identified 12 duties and 42 tasks. Each task comprised 1~5 task elements. Among tasks, 'assess the patient's general health status' was carried out most frequently. Nurse care coordinators perceived that 'check vital signs' and'strengthen patient competence to promote health behaviors' were more important than all other tasks. The most difficult task was 'develop professionalism as a nurse care coordinator'., Conclusion: The nurse care coordinators' roles developed in this study will serve as the key guidelines for human resource management of care coordinators. Further, job specifications for nurse care coordinators need to be developed, which is necessary for designing education and training programs. We also need to integrate primary health care as an essential component in nursing education., Competing Interests: The authors declared no conflict of interest., (© 2021 Korean Society of Nursing Science.)

Purpose: Inferior vena cava (IVC) filter tilt may lead to apex embedment and need for advanced retrieval techniques. This study assesses factors associated with filter tilt change over time and need for complex retrieval procedures., Materials and Methods: 252 consecutive patients underwent retrievable IVC filter placement and removal at a single academic institution over 58 months. 182 (72.2%) patients met inclusion criteria. IVC filters included 168 (92.3%) Gunther Tulip and 14 (7.7%) Option filters. The primary outcome was medial-to-lateral IVC filter tilt change between placement and retrieval. Secondary outcomes included advanced retrieval technique use and multiple retrieval attempts. Independent variables included demographics, IVC diameter, filter hook position relative to the renal veins, and dwell time. Associations were determined using student's t-tests, ANOVA, and linear and logistic regressions., Results: Mean IVC diameter at placement was 19.2 ± 3.3 mm. Mean filter tilts at placement and retrieval were 6.1 ± 4.9° and 5.2 ± 5.0°, respectively. Mean tilt change was 5.0 ± 5.0°. Larger IVC diameter was associated with greater filter tilt change (p = 0.0004). While IVC diameter did not independently predict retrieval difficulty, greater tilt change and prolonged dwell time were associated with increased advanced retrieval technique use (p = 0.01 and 0.002, respectively). Results were unchanged in a subgroup analysis of patients treated with Gunther Tulip filters., Conclusion: Larger IVC diameter predicts increased filter tilt change, which in turn is associated with challenging retrievals. Attention to IVC diameter during filter placement may anticipate tilt-related complications., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Infection, chronic pain and depression are considered risk factors for herpes zoster (HZ). However, the correlation between plantar fascial fibromatosis (PFF) and HZ remains unknown. This study investigated HZ risk in patients with PFF., Methods: Data was extracted from the Longitudinal Health Insurance Database 2000, which is a subsample of the Taiwan National Health Insurance (NHI) Research Database and contains 1 million NHI beneficiaries. Between 2000 and 2012, patients diagnosed as having PFF were included in the case cohort. Every case was age and sex-matched with individuals without PFF through 1:4 frequency matching (control cohort). The end of the follow-up was defined as December 31, 2013, the date of HZ diagnosis, death, emigration, or withdrawal from the NHI program., Results: In total, 4,729 patients were diagnosed as having PFF and were matched with 18,916 individuals without PFF. Patients with PFF were 1.23 times more likely to develop HZ than were those without PFF. Among those aged ≥65 years, patients with PFF had a higher HZ risk than did those without PFF (adjusted hazard ratio [aHR] = 1.48). Men with PFF had a significantly higher risk of HZ than did men without PFF (aHR = 1.44)., Conclusion: Patients with PFF, particularly older and male patients, having a high HZ risk and may thus be vaccinated for HZ., Competing Interests: The authors have declared that no competing interests exist.

Many citrus varieties are hybridized to improve their quality and to overcome the effects of climate change. However, there is limited information on the effect of the chemical profiles of hybrid varieties on their quality. In this study, we analyzed 10 citrus varieties and evaluated the correlation with their general characteristics and antioxidant activities. Chemical profiles, including the contents of sugars, organic acid compounds, flavonoids, limonoids, and carotenoids, which are related to taste, color, and health benefits, were significantly different depending on the citrus varieties, leading to different antioxidant capacities and general quality parameters. Based on these data, the correlations were investigated, and 10 citrus varieties were clustered into four groups-Changshou kumquat and Jeramon (cluster I); Setoka (cluster II-1); Natsumi, Satsuma mandarin, and Navel orange (cluster II-2); Kanpei, Tamnaneunbong, Saybyeolbong, and Shiranui (cluster II-3). Moreover, a metabolomic pathway was proposed. Although citrus peels were not analyzed and the sensory and functional qualities of the citrus varieties were not investigated in this study, our results are useful to better understand the relationship between citrus quality and metabolite profiles, which can provide basic information for the development and improvement of new citrus varieties.

Background: Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer., Methods: We collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI., Results: ICPi-AKI occurred at a median of 16 weeks (IQR 8-32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3-10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI., Conclusions: Patients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Noni fruits ( Morinda citrifolia ) are a source of phenolic bioactive compounds (scopoletin, alizarin, and rutin), which have antioxidant, antimicrobial, anticancer, and anti-inflammatory activities. In this study, subcritical water was applied to determine the extraction yields and kinetics of phenolic compounds from noni fruits. The scopoletin and alizarin yields increased with the increase in temperature from 100 to 140 °C, while that of rutin increased up to 120 °C and then decreased at 140 °C. The yields of all the compounds rapidly increased from 1 to 2 mL/min and then slightly up to 3 mL/min of water flow rate. The extraction kinetics were assessed using two mathematical models. The two-site kinetic desorption model had a better fit for all experimental conditions throughout the extraction cycle and best described the extraction kinetics of phenolic compounds from noni fruits. The diffusion coefficients of scopoletin and alizarin at 140 °C and 3 mL/min were 3.7- and 16.2-fold higher than those at 100 °C and 1 mL/min, respectively. The activation energies of alizarin were 2.9- to 8.5-fold higher than those of scopoletin at various flow rates. Thus, subcritical water could be an excellent solvent with higher extraction yields and shorter extraction times using an environmentally friendly solvent.