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Objective: To study the clinical, histopathological, and genetic features of large B-cell lymphoma (LBCL) with IRF4 rearrangement. Methods: Six patients presenting at our center between December 2017 and October 2021 were evaluated by pathological examination, fluorescence in situ hybridization, and next-generation sequencing. The relevant literature was reviewed. Results: ①The study sample included three males and three females with a median age of 33 years. Three tumors were in the tonsils, two in the lymphoid nodes, and one in the dorsal lump. All patients were treated using the RCDOP (rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, prednisone) regimen. All of them were alive at the time of follow-up in November 2021. ②Microscopic examination showed an entirely follicular pattern in one case and an entirely diffused pattern in 5 cases. The tumor cells were medium to large, and most of the lesions were dilatative with brisk mitotic activity ( n =five cases) and no starry sky pattern ( n =6 cases) . ③Four cases exhibited a GCB phenotype, and the other two exhibited a non-GCB phenotype. All of the cases were positive for CD20, PAX-5, MUM, and BCL6, and negative for CD5. Moreover, CD10, BCL2, and c-MYC were positive in 4, 3, and 2 cases, respectively.④IRF4 gene rearrangement was identified in all cases, BCL6 gene rearrangement was detected in 5 cases, and 2 cases were positive. BCL2 and MYC gene rearrangement were performed in 5 cases, all negative. ⑤Three paraffin tissue samples were used for next-generation sequencing, and lymphoma-related gene mutations such as IRF4, TP53, IGLL5, and MYD88 were detected in 3 cases. Conclusions: LBCL with IRF4 rearrangement is a rare entity with unique clinical, pathological, and genetic characteristics. This entity's pathogenesis, treatment options, and long-term prognosis still need to be explored further.

Background: β-1,4-endoglucanase (EG) is one of the three types of cellulases used in cellulose saccharification during lignocellulosic biofuel/biomaterial production. GsCelA is an EG secreted by the thermophilic bacterium Geobacillus sp. 70PC53 isolated from rice straw compost in southern Taiwan. This enzyme belongs to glycoside hydrolase family 5 (GH5) with a TIM-barrel structure common among all members of this family. GsCelA exhibits excellent lignocellulolytic activity and thermostability. In the course of investigating the regulation of this enzyme, it was fortuitously discovered that GsCelA undergoes a novel self-truncation/activation process that appears to be common among GH5 enzymes., Results: Three diverse Gram-positive bacterial GH5 EGs, but not a GH12 EG, undergo an unexpected self-truncation process by removing a part of their C-terminal region. This unique process has been studied in detail with GsCelA. The purified recombinant GsCelA was capable of removing a 53-amino-acid peptide from the C-terminus. Natural or engineered GsCelA truncated variants, with up to 60-amino-acid deletion from the C-terminus, exhibited higher specific activity and thermostability than the full-length enzyme. Interestingly, the C-terminal part that is removed in this self-truncation process is capable of binding to cellulosic substrates of EGs. The protein truncation, which is pH and temperature dependent, occurred between amino acids 315 and 316, but removal of these two amino acids did not stop the process. Furthermore, mutations of E142A and E231A, which are essential for EG activity, did not affect the protein self-truncation process. Conversely, two single amino acid substitution mutations affected the self-truncation activity without much impact on EG activities. In Geobacillus sp. 70PC53, the full-length GsCelA was first synthesized in the cell but progressively transformed into the truncated form and eventually secreted. The GsCelA self-truncation was not affected by standard protease inhibitors, but could be suppressed by EDTA and EGTA and enhanced by certain divalent ions, such as Ca 2+ , Mg 2+ , and Cu 2+ ., Conclusions: This study reveals novel insights into the strategy of Gram-positive bacteria for directing their GH5 EGs to the substrate, and then releasing the catalytic part for enhanced activity via a spontaneous self-truncation process., (© 2022. The Author(s).)

In this paper, we describe the application of the enantiomeric compounds YLC-1 - YLC-4 , each featuring a bulky spiro[fluorene-9,9'-phenanthren]-10'-one moiety, as both hole-transporting materials (HTMs) and interfacial layers in both n-i-p and p-i-n perovskite solar cells (PSCs). These HTMs contain an enantiomeric mixture and a variety of core units linked to triarylamine donors to extend the degree of π-conjugation. The n-i-p PSCs incorporating YLC-1(a) exhibited a power conversion efficiency (PCE) of 19.15% under AM 1.5G conditions (100 mW cm -2 ); this value was comparable with that obtained using spiro-OMeTAD as the HTM (18.25%). We obtained efficient and stable p-i-n PSCs having the dopant-free structure indium tin oxide (ITO)/NiO x /interfacial layer ( YLC )/perovskite/PC 61 BM/BCP/Ag. The presence of the spiro-based compounds YLC-1 and YLC-2 efficiently passivated the interfacial and grain boundary defects of the perovskite and enhanced the sizes of its grains, more so than did YLC-3 and YLC-4 . These spiro-based YLC derivatives packed densely and functioned as Lewis bases to coordinate Pb and Ni ions in the perovskite and NiO x layers, respectively. Together, the effects of smaller grain boundaries and defect passivation of the perovskite enhanced the optoelectronic properties of the PSCs. The photoinduced charge carrier extraction in the linearly increasing voltage (photo-CELIV) curves of NiO x /YLC-1(a) showed the faster carrier transport 3.3 × 10 -3 cm 2 V -1 s -1 , which improved the carrier mobility, supporting the notion of defect passivation of the perovskite. The best-performing NiO x / YLC-1(a) device provided a short-circuit current density ( J SC ) of 22.88 mA cm -2 , an open-circuit voltage ( V OC ) of 1.10 V, and a fill factor (FF) of 80.93%, corresponding to an overall PCE of 20.37%. In addition, the PCEs of the NiO x / YLC-1(a) and NiO x / YLC-4(b) PSC devices underwent decays of only 98.1 and 97.0% of their original values after 41 days under an Ar atmosphere. Thus, these YLC derivatives passivated the NiO x surface and optimized the film quality of perovskites, thereby leading to superior PCEs of their respective PSCs.

Background: Atherosclerosis and vascular inflammatory response have been considered as risk factors for non-typhoidal Salmonella (NTS) vascular infection. The study aims to assess the risk of vascular infection by measuring atherosclerosis severity, NTS vascular infection (NTSVI) score, and serum levels of inflammatory markers in people with NTS bacteremia., Methods: A prospective observational study was conducted in two medical centers and two regional hospitals. Adults aged ≥50 years with NTS bacteremia who underwent computed tomography (CT) scan for revealing vascular infections were enrolled. The degree of atherosclerosis was scaled by a calcium score determined by a CT scan. Serum concentrations of inflammatory biomarkers were determined in the patients enrolled in a medical center., Results: Fourteen (20.3%) of 69 patients with NTS bacteremia had vascular infections. Calcium scores over the thoracic (12,540 vs. 3,261, P = 0.0005) and abdominal (9755 vs. 3,461, P = 0.0006) aorta of those with vascular infections were higher than those without vascular infection. All vascular infections were present in the high-risk group (NTSVI score ≥1), yielding a sensitivity of 100% and specificity of 30.9%. Among 17 low-risk patients (NTSVI score <1), none had vascular infections, resulting in a negative predictive value of 100%. Higher plasma concentrations of IL-1β were detected in the cases of vascular infection than those in the control group (23.6 vs. 1.06 pg/mL, P = 0.001)., Conclusion: Atherosclerosis of the aorta which is associated with a positive NTSVI score can predict the occurrence of vascular infections and serum IL-1β could be a biomarker for vascular infection in patients with NTS bacteremia., Competing Interests: Declaration of competing interest All authors reported no conflicts of interest., (Copyright © 2021. Published by Elsevier B.V.)

Longibrachiamide A (1), a new 20-residue peptaibol, along with three known ones (2-4), were isolated from the fungus Trichoderma longibrachiatum Rifai DMG-3-1-1, isolated from a mushroom Clitocybe nebularis (Batsch) P. Kumm, which was collected from coniferous forest of northeast China in our previous work. The structure of longibrachiamide A (1) was determined by its NMR and ESI-MS/MS data, the absolute configuration of 1 was further determined by Marfey's analyses. And the complete NMR data of 2-4 were also reported for the first time. The similar CD spectra of 1-4 showed that they all had mixed 3 10 -/α-helical conformations. Compounds 1-4 showed strong cytotoxicities against BV2, A549 and MCF-7 cells, and also showed moderate inhibitory effects against the tested Gram-positive bacteria, including MRSA T144 and VRE-10., (© 2022 Wiley-VHCA AG, Zurich, Switzerland.)

Objective: The UPrEPU mobile app is a self-monitoring system to enable men who have sex with men to optimize their pre-exposure prophylaxis adherence for HIV prevention. The app was designed to accommodate a rather complicated event-driven dosing schedule. We aim to evaluate the usability of the UPrEPU app and its effectiveness in improving adherence monitoring., Methods: From May to October 2020, 35 participants were enrolled for the usability study and followed up for 4 months. Blood samples for the drug concentration in the dried blood spots were obtained once during the second to fourth follow-up visits. The effectiveness of adherence monitoring was analyzed using Cohen's kappa statistic to calculate the concordance between the average number of pills taken and drug concentration in the dried blood spots., Results: Overall retention was 91.4% (32 participants) at the end of the study. Participants used the app for a mean of 29 days and made 2565 data entries in total, with an average of 76 data entries. The average systematic usability scale score for the app was 71.5, indicating acceptable usability. Slight agreement was reached between the dried blood spots measurement and the number of pills taken and recorded in the app (weighted kappa: 0.21)., Conclusions: Our user-centered UPrEPU app demonstrated that it could accommodate both daily and event-driven dosing schedules for men who have sex with men clients with acceptable usability scores. We confirmed that complex behaviors such as different drug-dosing regimens that are contingent on sexual behaviors could be incorporated into the design of a mobile app., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Nasopharyngeal carcinoma (NPC) is prevalent in East Asia and causes increased health burden. Elucidating the regulatory mechanism of NPC progression is important for understanding the pathogenesis of NPC and developing novel therapeutic strategies. Nasopharyngeal carcinoma and normal tissues were collected. Nasopharyngeal carcinoma cell proliferation, migration, and invasion were evaluated using CCK-8, colony formation, wound healing, and transwell assays, respectively. A xenograft mouse model of NPC was established to analyze NPC cell growth and metastasis in vivo. The expression of miR-106a-5p, FBXW7, TRIM24, and SRGN was determined with RT-qPCR and Western blot. MiR-106a-5p, TRIM24, and SRGN were upregulated, and FBXW7 was downregulated in NPC tissues and cells. Exosomal miR-106a-5p could enter NPC cells, and its overexpression promoted the proliferation, migration, invasion, and metastasis of NPC cells, which were suppressed by knockdown of exosomal miR-106a-5p. MiR-106a-5p targeted FBXW7 to regulate FBXW7-mediated degradation of TRIM24. Furthermore, TRIM24 regulated SRGN expression by binding to its promoter in NPC cells. Suppression of exosomal miR-106a-5p attenuated NPC growth and metastasis through the FBXW7-TRIM24-SRGN axis in vivo. Exosomal miR-106a-5p accelerated the progression of NPC through the FBXW7-TRIM24-SRGN axis. Our study elucidates novel regulatory mechanisms of NPC progression and provides potential exosome-based therapeutic strategies for NPC., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

We synthesized multiple cinnamils and quinoxalines to evaluate their anticancer activity. Cinnamils were used as precursors for quinoxalines via condensation with 1,2-diaminobenzene. Among the 26 synthesized compounds reported in this article, we found that cinnamil 3l exhibited its inhibitory effect with an IC 50 value of 1.45 ± 0.98 μM, significantly higher than doxorubicin (8.5 ± 0.85 μM) against pancreatic cancer cells (PANC-1). Additionally, cinnamil 3l (IC 50 10.98 ± 3.63 μM) showed less cytotoxicity than doxorubicin to Hs68 cells (0.92 ± 1.11 μM). The colony formation assay demonstrated that 3l obviously decreased the PANC-1 cell viability, and Western blot assays confirmed that 3l markedly induced apoptosis of PANC-1 cells through Bax, Bcl-2, and caspase 3 signaling cascades. These results demonstrate that cinnamil 3l has great potential to be further developed as a promising chemotherapeutic agent for pancreatic cancer., (© 2022 Deutsche Pharmazeutische Gesellschaft.)

Objective: This study was to explore the difference and significance of parietal pleura invasion and rib invasion in pathological T classification with non-small cell lung cancer., Methods: A total of 8681 patients after lung resection were selected to perform analyses. Multivariable Cox analysis was used to identify the mortality differences in patients between parietal pleura invasion and rib invasion. Eligible patients with chest wall invasion were re-categorized according to the prognosis. Cancer-specific survival curves for different pathological T (pT) classifications were presented., Results: There were 466 patients considered parietal pleura invasion, and 237 patients served as rib invasion. Cases with rib invasion had poorer survival than those with the invasion of parietal pleura (adjusted hazard ratio [HR]= 1.627, P =0.004). In the cohort for parietal pleura invasion, patients with tumor size ≤5cm reached more satisfactory survival outcomes than patients with tumor size >5cm (unadjusted HR =1.598, P =0.006). However, there was no predictive difference in the cohort of rib invasion. The results of the multivariable analysis revealed that the mortality with parietal pleura invasion plus tumor size ≤5cm were similar to patients with classification pT3 ( P =0.761), and patients for parietal pleura invasion plus tumor size >5cm and pT4 had no stratified survival outcome (P =0.809). Patients identified as rib invasion had a poorer prognosis than patients for pT4 ( P =0.037)., Conclusions: Rib invasion has a poorer prognosis than pT4. Patients with parietal pleura invasion and tumor size with 5.1-7.0cm could be appropriately up-classified from pT3 to pT4., 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 Wu, Li, Li, Qiu, Xu, Lin, Ma, Li and Xie.)

In this paper, the syntheses of twelve asymmetric curcumin analogs using Pabon's method are reported. Generally, the previously reported yields of asymmetric curcuminoids, such as 9a (53%), 9c (38%), and 9k (38%), have been moderate or low. Herein, we propose that the low yields were due to the presence of water and n -BuNH 2 in the reaction media. To prove this formulated hypothesis, we have demonstrated that the yields can be improved by adding molecular sieves (MS) (4 Å) to the reaction mixture, thus reducing the interference of water. Therefore, improved yields (41-76%) were obtained, except for 9b (36.7%), 9g (34%), and 9l (39.5%). Furthermore, compounds 9b , 9d , 9e , 9f , 9g , 9h , 9i , 9j , and 9l are reported herein for the first time. The structures of these synthetic compounds were determined by spectroscopic and mass spectrometry analyses. The free radical scavenging ability of these synthetic asymmetric curcuminoids was evaluated and compared to that of the positive control butylated hydroxytoluene (BHT). Among the synthesized asymmetric curcuminoids, compounds 9a (IC 50 = 37.57 ± 0.89 μM) and 9e (IC 50 = 37.17 ± 1.76 μM) possessed effective 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging abilities, and compounds 9h (IC 50 = 11.36 ± 0.65 μM) and 9i (IC 50 = 10.91 ± 0.77 μM) displayed potent 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) radical scavenging abilities comparable to that of curcumin (IC 50 = 10.14 ± 1.04 μM). Furthermore, all the synthetic asymmetric curcuminoids were more active than BHT.

Age-associated obesity and muscle atrophy (sarcopenia) are intimately connected and are reciprocally regulated by adipose tissue and skeletal muscle dysfunction. During ageing, adipose inflammation leads to the redistribution of fat to the intra-abdominal area (visceral fat) and fatty infiltrations in skeletal muscles, resulting in decreased overall strength and functionality. Lipids and their derivatives accumulate both within and between muscle cells, inducing mitochondrial dysfunction, disturbing β-oxidation of fatty acids, and enhancing reactive oxygen species (ROS) production, leading to lipotoxicity and insulin resistance, as well as enhanced secretion of some pro-inflammatory cytokines. In turn, these muscle-secreted cytokines may exacerbate adipose tissue atrophy, support chronic low-grade inflammation, and establish a vicious cycle of local hyperlipidaemia, insulin resistance, and inflammation that spreads systemically, thus promoting the development of sarcopenic obesity (SO). We call this the metabaging cycle. Patients with SO show an increased risk of systemic insulin resistance, systemic inflammation, associated chronic diseases, and the subsequent progression to full-blown sarcopenia and even cachexia. Meanwhile in many cardiometabolic diseases, the ostensibly protective effect of obesity in extremely elderly subjects, also known as the 'obesity paradox', could possibly be explained by our theory that many elderly subjects with normal body mass index might actually harbour SO to various degrees, before it progresses to full-blown severe sarcopenia. Our review outlines current knowledge concerning the possible chain of causation between sarcopenia and obesity, proposes a solution to the obesity paradox, and the role of fat mass in ageing., (© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

A new meroterpene, chrysomutanin ( 1 ), two new meroterpenoids ( 4 and 5 ) together with nine known ones were isolated from the diethyl sulphate (DES) mutant 3d10-01 of the marine-derived fungus Penicillium chrysogenum S-3-25. The structures of the isolated compounds were determined by their spectroscopic data, and the absolute configuration of 1 was determined by Rh 2 -induced electrical circular dichroism (ECD) analysis or by comparison of the measured ECD with that of the known compounds. The cytotoxic activity was preliminarily evaluated against five human cancer cell lines. HPLC-UV analysis showed that compounds 1 - 12 were all newly produced by the mutant, and were not detected from the initial strain S-3-25. Chrysomutanin ( 1 ) is a new member with a chain sesquiterpene unit to the family of meroterpenes. Present results confirm that DES mutagenesis strategy is an effective method to exploit the dormant metabolites of fungi.

This study presents a U-shaped dual-frequency-reconfigurable liquid-metal monopole antenna. Eutectic Gallium-Indium (EGaIn) was used as a conductive fluid and filled in the two branches of the U-shaped glass tube. A precision syringe pump was connected to one of the branches of the U-shaped tube by a silicone tube to drive EGaIn, forming a height difference between the two liquid levels. When the height of liquid metal in the two branches met the initial condition of L 1 = L 2 = 10 mm, and L 1 increased from 10 mm to 18 mm, the two branches obtained two working bandwidths of 2.27-4.98 GHz and 2.71-8.58 GHz, respectively. The maximum peak gain was 4.00 dBi. The initial amount of EGaIn also affected the available operating bandwidth. When the liquid metal was perfused according to the initial condition: L 1 = L 2 = 12 mm, and L 1 was adjusted within the range of 12-20 mm, the two branches had the corresponding working bandwidths of 2.18-4.32 GHz and 2.57-9.09 GHz, and the measured maximum peak gain was 3.72 dBi. The simulation and measurement data corresponded well. A series of dual-frequency-reconfigurable antennas can be obtained by changing the initial amount of EGaIn. This series of antennas may have broad application prospects in fields such as base stations and navigation.

Portulaca oleracea is a well-known species for traditional medicine and food homology in Taiwan. In traditional medicine, P. oleracea is also used to treat gastrointestinal disorders, liver inflammation, fever, severe inflammation, and headaches. We investigated antioxidant, anti-tyrosinase, and anti-α-glucosidase activities of various solvent extracts and major bioactive components from P. oleracea . Ethanol and acetone extracts showed potent DPPH, ABTS, and hydroxyl radical scavenging activities. Chloroform and n -hexane extracts displayed significant superoxide radical scavenging activity. Furthermore, ethyl acetate and acetone extracts of P. oleracea showed potent anti-tyrosinase and anti-α-glucosidase activities. Examined and compared to the various solvent extracts for their chemical compositions using HPLC analysis, we isolated seven major compounds and analyzed their antioxidant, anti-tyrosinase, and anti-α-glucosidase activities. Seven active compounds of P. oleracea , especially quercetin, rosmarinic acid, and kaempferol, exhibited obvious antioxidant, anti-tyrosinase, and anti-α-glucosidase activities. The molecular docking model and the hydrophilic interactive mode of tyrosinase and α-glucosidase revealed that active compounds might have a higher antagonistic effect than commonly inhibitors. Our result shows that the active solvent extracts and their components of P. oleracea have the potential as natural antioxidants, tyrosinase and α-glucosidase inhibitors. Our results suggest that the active solvent extracts of P. oleracea and their components have potential as natural antioxidants, tyrosinase and α-glucosidase inhibitors.

Background: Dysbiosis of oral microbiota is the cause of many diseases related to oral and general health. However, few Asia-based studies have evaluated the role of oral microbiota in patients receiving long-term care. Thus, new indications are needed for early prevention and risk management based on information derived from the oral microbiota., Methods: We used next-generation sequencing (NGS) to identify the oral bacterial composition and abundance in patients receiving long-term care: 20 from the outpatient department (OPD) and 20 home-care patients. Their microbial compositions, taxonomy, and alpha/beta diversity were characterized., Results: Microbiota from the two groups showed different diversity and homogeneity, as well as distinct bacterial species. A more diverse and stable microbial population was observed among OPD patients. Our findings indicated that home-care patients had a higher risk of oral diseases due to the existence of dominant species and a less stable microbial community., Conclusion: This work was the first in Taiwan to use NGS to investigate the oral microbiota of long-term care patients. Our study demonstrated the potential use of dominant bacterial species as biomarkers for the risk management of posttreatment complications., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

When listening to music, people are excited by the musical cues immediately before rewarding passages. More generally, listeners attend to the antecedent cues of a salient musical event irrespective of its emotional valence. The present study used functional magnetic resonance imaging to investigate the behavioral and cognitive mechanisms underlying the cued anticipation of the main theme's recurrence in sonata form. Half of the main themes in the musical stimuli were of a joyful character, half a tragic character. Activity in the premotor cortex suggests that around the main theme's recurrence, the participants tended to covertly hum along with music. The anterior thalamus, pre-supplementary motor area (preSMA), posterior cerebellum, inferior frontal junction (IFJ), and auditory cortex showed increased activity for the antecedent cues of the themes, relative to the middle-last part of the themes. Increased activity in the anterior thalamus may reflect its role in guiding attention towards stimuli that reliably predict important outcomes. The preSMA and posterior cerebellum may support sequence processing, fine-grained auditory imagery, and fine adjustments to humming according to auditory inputs. The IFJ might orchestrate the attention allocation to motor simulation and goal-driven attention. These findings highlight the attention control and audiomotor components of musical anticipation.

Brain synchronizations are orchestrated from neuronal oscillations through frequency interactions, such as the alpha rhythm during relaxation. Nevertheless, how the intrinsic interaction forges functional integrity across brain segregations remains elusive, thereby motivating recent studies to localize frequency interactions of resting-state fMRI (rs-fMRI). To this point, we aim to unveil the fMRI-based spectral interactions using the time-frequency (TF) analysis; however, Fourier-based TF analyses impose restrictions on revealing frequency interactions given the limited time points in fMRI signals. Instead of using the Fourier-based wavelet analysis to identify the fMRI frequency of interests, we employed the Hilbert-Huang transform (HHT) for probing the specific frequency contribution to the functional integration, called ensemble spectral interaction (ESI). By simulating data with time-variant frequency changes, we demonstrated the Hilbert TF maps with high spectro-temporal resolution and full accessibility in comparison with the wavelet TF maps. By detecting amplitude-to-amplitude frequency couplings (AAC) across brain regions, we elucidated the ESI disparity between the eye-closed (EC) and eye-open (EO) conditions in rs-fMRI. In the visual network, the strength of the spectral interaction within 0.03-0.04 Hz was amplified in EC compared with that in EO condition, whereas a canonical connectivity analysis did not present differences between conditions. Collectively, leveraging from the instantaneous frequency of HHT, we firstly addressed the ESI technique to map the fMRI-based functional connectivity in a brand-new AAC perspective. The ESI possesses potential in elucidating the functional connectivity at specific frequency bins, thereby providing additional diagnostic merits for future clinical neuroscience.

Objectives: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China., Methods: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups., Results: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth ( P <0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group ( P <0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia ( P <0.05)., Conclusions: There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.

Background: The efficacy of highly active antiretroviral therapy (HAART) can be estimated by the immunological response and the incidence of opportunistic infections., Objective: This study aimed at evaluating the effectiveness of different durations of HAART in terms of immunological response markers (CD4 count and CD4/CD8 ratio) along with disease progression markers (incidence of oral lesions) in Chinese patients with HIV., Methods: This single-center, retrospective, and real-world study included patients with HIV, grouped into a treatment group and treatment-naïve group, of which the former was further divided into 6, 12, and 18 months based on the treatment duration. The CD4 and CD8 cell counts were analyzed by the FACSCalibur flow cytometry. Kruskal-Wallis test was applied to determine the outcome of different duration of HAART. Oral examination was carried out according to the WHO type IV examination., Results: In 246 patients with HIV, CD4 counts increased significantly post-HAART compared to pre-HAART in all three treatment groups (P<.001), while CD8 count decreased significantly (P<.05) in all three treated groups. A significant association of HAART with the CD4/CD8 ratio was observed (P<.001). A significant increase in CD4 count was observed between 12-months and 18-months treatment groups (P<.05). The occurrence of oral lesions reduced significantly in the treatment group., Conclusion: We observed a better response to the HAART regimen with 18-months of duration than 12-months and 6-months therapies and reduction in oral lesions., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Through an RNA-seq analysis of an adult patient with unclassifiable myelodysplastic/myeloproliferative neoplasms (MDS/MPN-U), we identified a rare PDGFRB fusion partner gene, PCM1. Conventional chromosome karyotype analysis showed abnormal clones of t(5;8)(q32;p22), and fluorescence in situ hybridization (FISH) confirmed rearrangement of the PDGFRB gene. Reverse transcription PCR (RT-PCR) and Sanger sequencing further confirmed that exon 30 of the PCM1 gene was fused with exon 11 of PDGFRB in frame, and the fusion event was accompanied by a 14 bp deletion of exon 11 of PDGFRB. After low-dose imatinib treatment, the patient achieved complete molecular remission. This study not only broadens the understanding of myeloid/lymphoid neoplasms with PDGFRB rearrangement but also reflects the vital role of RNA-seq in identifying PDGFRB rearrangements., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Objectives: Research shows that compassion from others and from the self may enable university students to face, overcome, and bounce back from adversity and generate a greater sense of thriving and meaning in life. However, the underlying processes are largely unknown. The present study aimed to examine the associations of compassion with psychological distress, flourishing, and meaning in life among university students and explore the mechanisms underlying these associations., Methods: A total of 536 Hong Kong university students completed questionnaires measuring their experiences of compassion from others, self-compassion, resilience, psychological distress, flourishing, and meaning in life., Results: Serial mediation analyses showed that compassion from others was associated positively with self-compassion, which was, in turn, linked to greater resilience and consequently lower levels of psychological distress and higher levels of flourishing and meaning in life., Conclusions: Our findings reveal the associations of compassion from others and self-compassion with the well-being and life meaning of university students. The findings highlight the importance of being open and receptive to love and kindness from others. The findings also point to the importance of developing a caring attitude toward oneself., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s) 2022.)

Background: New innovative technologies, such as mobile apps, have been developed to increase pre-exposure prophylaxis (PrEP) adherence and the use of log sex diaries. The contiguity of mobile apps reduces the recall bias that generally affects reported condom and PrEP use. However, none of the currently used mobile apps were designed for event-driven PrEP users, and few studies have demonstrated the potential usage of sex diary data to facilitate the understanding of the different HIV risks among heterogeneous profiles of sex diaries and PrEP use., Objective: We aim to discriminate the heterogeneous profiles of sex events and PrEP use and examine the risk of condomless anal sex among different types of sex events., Methods: We recruited 35 adult men who have sex with men from two medical centers in Taiwan since May 2020 and followed up for four months. Participants were on PrEP or willing to take PrEP. They were asked to log their sex events, PrEP use, and dosing regimens on a mobile app to improve their PrEP adherence. Latent class analysis was used to distinguish profiles of sex events and PrEP use. Indicators included correct intake of PrEP for each sex event, participants' sexual positioning, partner's HIV status, and age., Results: A total of 551 sex events were classified into three classes by latent class analysis: PrEP nonadherent flip-flopping (234/551, 42%), PrEP imperfect-adherent power bottoming (284/551, 52%), and PrEP adherent serodiscordant topping (33/551, 6%). "PrEP nonadherent flip-flopping" sex events were more likely to involve condomless anal sex than "PrEP imperfect-adherent power bottoming" (OR 1.83, 95% CI 1.03-3.25) after considering random intercepts for individuals, and this class needed to increase their PrEP adherence and use of condoms. "PrEP imperfect-adherent power bottoming" realized their own risk and packaged PrEP with condoms to protect themselves. Up to 99% (32/33) of sex events in "PrEP adherent serodiscordant topping" were protected by PrEP, but all of the sex events in this group were condomless., Conclusions: Using the sex diary data could advance the capacity to identify high-risk groups. HIV prevention strategy should be more flexible and combine PrEP with condom use for future HIV prevention., (©Yi-Fang Yu, Huei-Jiuan Wu, Stephane Wen-Wei Ku, Po-Hsien Huang, Chia-Wen Li, Poyao Huang, Carol Strong. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 23.12.2021.)

Autoimmune polyglandular syndrome type 3 variant (APS3v) refers to an autoimmune condition in which both type 1 diabetes (T1D) and autoimmune thyroiditis (AITD) develop in the same individual. HLA-DR3 confers the strongest susceptibility to APS3v. Previously we reported a unique amino acid signature pocket that predisposes to APS3v. We found that this pocket is flexible and can trigger APS3v by presenting both thyroid (Tg.1571, TPO.758) and islet (GAD.492) peptides to induce autoimmune response. We hypothesized that blocking the specific APS3v-HLA-DR3 pocket from presenting thyroid/islet antigens can block the autoimmune response in APS3v. To test this hypothesis we performed a virtual screen of small molecules blocking APS3v-HLA-DR3, and identified 11 small molecules hits that were predicted to block APS3v-HLA-DR3. Using the baculovirus-produced recombinant APS3v-HLA-DR3 protein we tested the 11 small molecules in an in vitro binding assay. We validated 4 small molecule hits, S9, S5, S53 and S15, that could block the APS3v-HLA-DR3 pocket in vitro . We then developed a novel humanized APS3v mouse model induced by co-immunizing a peptide mix of Tg.1571, TPO.758 and GAD.492. The immunized mice developed strong T-cell and antibody responses to the thyroid/islet peptides, as well as mouse thyroglobulin. In addition, the mice showed significantly lower free T4 levels compared to controls. Using the APS3v mouse model, we showed that one of the 4 small molecules, Cepharanthine (S53), blocked T-cell activation by thyroid/islet peptides ex vivo and in vivo . These findings suggested Cepharanthine may have a therapeutic potential in APS3v patients carrying the specific APS3v-HLA-DR3 pocket., Competing Interests: YT declares that he was previously (1/2015 – 6/2017) the principal investigator on a basic research project jointly funded by the Juvenile Diabetes Research Foundation and Pfizer. The current manuscript is not related to that research project. YT and CL declare that they submitted a patent application for Cepharanthine as a treatment for APS3v and T1D. YT, RO, and LF have additional patent applications that are not related to the content of this manuscript. The remaining 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 © 2021 Li, Osman, Menconi, Faustino, Kim, Clarke, Hou and Tomer.)

Background: Cerebral blood flow (CBF) and the morphology of the cerebral arteries are important for characterizing cerebrovascular disease. Silent magnetic resonance angiography (Silent MRA) is a MRA technique focusing on arterial structural delineation. This study was conducted to investigate the correlation between Silent MRA and CBF quantification, which has not yet been reported., Methods: Both the Silent MRA and time-of-flight magnetic resonance angiography scans were applied in seventeen healthy participants to acquire the arterial structure and to find arterial intensities. Phase-contrast MRA (PC-MRA) was then used to perform the quantitative CBF measurement of 13 cerebral arteries. Due to different dataset baseline signal level of Silent MRA, the signal intensities of the selected 13 cerebral arteries were normalized to the selected ROIs of bilateral internal carotid arteries. The normalized signal intensities were used to determine the relationship between Silent MRA and CBF., Results: The image intensity distribution of arterial regions generated by Silent MRA showed similar laminar shape as the phase distribution by PC-MRA (correlation coefficient > 0.62). Moreover, in both the results of individual and group-leveled analysis, the intensity value of arterial regions by Silent MRA showed positively correlation with the CBF by PC-MRA. The coefficient of determination (R 2 ) of individual trends ranged from 0.242 to 0.956, and the R 2 of group-leveled result was 0.550., Conclusions: This study demonstrates that Silent MRA provides valuable CBF information despite arterial structure, rendering it a potential tool for screening for cerebrovascular disease., (© 2021. The Author(s).)

In response to the COVID-19 pandemic, Taiwan has been one of the best performers in the world with extremely low infections and deaths. This success can be attributed to the long experiences dealing with natural disasters and communicable diseases. However, with different disastrous characteristics, the disaster management systems for communicable diseases and natural disasters are very different in terms of laws, plans, frameworks, and emergency operations. Taking the response to COVID-19 pandemic as a study subject, we found that disaster management for communicable diseases can be improved through a comparison with natural disasters, and vice versa. First, having wider and longer impacts than natural disasters, the plans and framework for communicable diseases in Taiwan focus more on national and regional scales. Local governments would need more capacity support including budgets and training to conduct investigations and quarantine during the COVID-19 pandemic. Second, for quick response, the emergency operation for communicable diseases was designed to be more flexible than that for natural disasters by giving the commander more authority to adjust to the circumstances. The commanding system requires a more objective consultation group to prevent arbitrary decisions against the COVID-19 pandemic. Finally, risk governance is important for communicable diseases as well as for natural disasters. Additional efforts should be made to enhance vulnerability assessment, disaster reduction, and risk communication for shaping responses and policies in an efficient and coordinating way., 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 © 2021 Wang, Chen, Lee, You, Li, Jang and Shieh.)

Background: Despite clinical success with anti-spike vaccines, the effectiveness of neutralizing antibodies and vaccines has been compromised by rapidly spreading SARS-CoV-2 variants. Viruses can hijack the glycosylation machinery of host cells to shield themselves from the host's immune response and attenuate antibody efficiency. However, it remains unclear if targeting glycosylation on viral spike protein can impair infectivity of SARS-CoV-2 and its variants., Methods: We adopted flow cytometry, ELISA, and BioLayer interferometry approaches to assess binding of glycosylated or deglycosylated spike with ACE2. Viral entry was determined by luciferase, immunoblotting, and immunofluorescence assays. Genome-wide association study (GWAS) revealed a significant relationship between STT3A and COVID-19 severity. NF-κB/STT3A-regulated N-glycosylation was investigated by gene knockdown, chromatin immunoprecipitation, and promoter assay. We developed an antibody-drug conjugate (ADC) that couples non-neutralization anti-spike antibody with NGI-1 (4G10-ADC) to specifically target SARS-CoV-2-infected cells., Findings: The receptor binding domain and three distinct SARS-CoV-2 surface N-glycosylation sites among 57,311 spike proteins retrieved from the NCBI-Virus-database are highly evolutionarily conserved (99.67%) and are involved in ACE2 interaction. STT3A is a key glycosyltransferase catalyzing spike glycosylation and is positively correlated with COVID-19 severity. We found that inhibiting STT3A using N-linked glycosylation inhibitor-1 (NGI-1) impaired SARS-CoV-2 infectivity and that of its variants [Alpha (B.1.1.7) and Beta (B.1.351)]. Most importantly, 4G10-ADC enters SARS-CoV-2-infected cells and NGI-1 is subsequently released to deglycosylate spike protein, thereby reinforcing the neutralizing abilities of antibodies, vaccines, or convalescent sera and reducing SARS-CoV-2 variant infectivity., Interpretation: Our results indicate that targeting evolutionarily-conserved STT3A-mediated glycosylation via an ADC can exert profound impacts on SARS-CoV-2 variant infectivity. Thus, we have identified a novel deglycosylation method suitable for eradicating SARS-CoV-2 variant infection in vitro., Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section., Competing Interests: Declaration of Competing Interest H.-C. H., Y.-J. L., and C.-W.L. declared inventorship with US/ 63/262,926 patent listed on 2021, ANTIBODY-DRUG CONJUGATE FOR REDUCING MEMBRANE RECEPTOR GLYCOSYLATION. The remaining authors declare no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

(1) Background: This study aimed to determine the association between the use of efavirenz and depressive disorders among human immunodeficiency virus (HIV)-infected patients. (2) Methods: A retrospective cohort study was conducted using Taiwan's National Health Insurance Database. We identified patients receiving anti-retroviral therapy (ART) between 2000 and 2009; these patients were followed until 2010 for diagnoses of depressive disorders using the Cox proportional hazard model to estimate hazard ratios. (3) Results: After up to 11 years of follow-up, the incidence of depressive disorders for the efavirenz-treated group was estimated at 12.2/1000 person-years (PYs), and the control group was at 12.5/1000 PY ( p = 0.822). The independent risk factors for depressive disorders included an insurance premium of less than NTD 17,820 (New Taiwan Dollars-NTD) (adjusted hazard ratio (aHR) 2.59, 95% confidence interval (CI), 1.79-3.76, p < 0.001), and between NTD 17,821 and NTD 26,400 (aHR 1.55, 95% CI, 1.04-2.31, p = 0.030), living in Southern Taiwan (aHR 1.49, 95% CI, 1.21-1.84, p = 0.002), and with a psychiatric history (excluding depressive disorders) (aHR 4.59, 95% CI, 3.51-6.01, p = 0.030). (4) Conclusions: This study concluded that ART-treated patients with a past history of psychiatric disorders, lower insurance premium, and living in Southern Taiwan have an increased risk of depressive disorders, which are not associated with the use of efavirenz.

Background: Arsenic (As 3+ ) is a carcinogen with considerable environmental and occupational relevancy. Its mechanism of action and methods of prevention remain to be investigated. Previous studies have demonstrated that ROS is responsible for As 3+ -induced cell transformation, which is considered as the first stage of As 3+ carcinogenesis. The NF-E2 p45-related factor-2 (Nrf2) signaling pathway regulates the cellular antioxidant response, and activation of Nrf2 has recently been shown to limit oxidative damage following exposure to As 3+ METHODS AND RESULTS: In this study, molecular docking was used to virtually screen natural antioxidant chemical databases and identify molecules that interact with the ligand-binding site of Keap1 (PDB code 4L7B). The cell-based assays and molecular docking findings revealed that curcumin has the best inhibitory activity against Keap1-4L7B. Co-immunoprecipitation (Co-IP) results indicated that curcumin is a potent Keap1 Kelch domain-dependent Nrf2 activator that stabilizes Nrf2 by hindering its ubiquitination. The increased activation of Nrf2 and its target antioxidant genes by curcumin could significantly decrease As 3+ -generated ROS. Moreover, curcumin induced autophagy in As 3+ -treated BEAS-2B via inducing autophagy by the formation of a p62/LC-3 complex and increasing autophagic flux by promoting transcription factor EB (TFEB) and lysosome-associated membrane protein 1 (LAMP1) expression. Knockdown of Nrf2 abolished curcumin-induced autophagy and downregulated ROS. Further studies showed that inhibition of autophagosome and lysosome fusion with bafilomycin a1 (BafA1) could block curcumin and prevented As 3+ -induced cell transformation. These results demonstrated that curcumin prevents As 3+ -induced cell transformation by inducing autophagy via the activation of the Nrf2 signaling pathway in BEAS-2B cells. However, overexpression of Keap-1 showed a constitutively high level of Nrf2 in As 3+ -transformed BEAS-2B cells (AsT) is Keap1-independent regulation. Overexpression of Nrf2 in AsT demonstrated that curcumin increased ROS levels and induced cell apoptosis via the downregulation of Nrf2. Further studies showed that curcumin decreased the Nrf2 level in AsT by activating GSK-3β to inhibit the activation of PI3K/AKT. Co-IP assay results showed that curcumin promoted the interaction of Nrf2 with the GSK-3β/β-TrCP axis and ubiquitin. Moreover, the inhibition of GSK-3β reversed Nrf2 expression in curcumin-treated AsT, indicating that the decrease in Nrf2 is due to activation of the GSK-3β/β-TrCP ubiquitination pathway. Furthermore, in vitro and in vivo results showed that curcumin induced cell apoptosis, and had anti-angiogenesis and anti-tumorigenesis effects as a result of activating the GSK-3β/β-TrCP ubiquitination pathway and subsequent decrease in Nrf2., Conclusions: Taken together, in the first stage, curcumin activated Nrf2, decreased ROS, and induced autophagy in normal cells to prevent As 3+ -induced cell transformation. In the second stage, curcumin promoted ROS and apoptosis and inhibited angiogenesis via inhibition of constitutive expression of Nrf2 in AsT to prevent tumorigenesis. Our results suggest that antioxidant natural compounds such as curcumin can be evaluated as potential candidates for complementary therapies in the treatment of As 3+ -induced carcinogenesis., (© 2021. The Author(s).)

To explore how the immune system controls clearance of SARS-CoV-2, we used a single-cell, mass cytometry-based proteomics platform to profile the immune systems of 21 patients who had recovered from SARS-CoV-2 infection without need for admission to an intensive care unit or for mechanical ventilation. We focused on receptors involved in interactions between immune cells and virus-infected cells. We found that the diversity of receptor repertoires on natural killer (NK) cells was negatively correlated with the viral clearance rate. In addition, NK subsets expressing the receptor DNAM1 were increased in patients who more rapidly recovered from infection. Ex vivo functional studies revealed that NK subpopulations with high DNAM1 expression had cytolytic activities in response to target cell stimulation. We also found that SARS-CoV-2 infection induced the expression of CD155 and nectin-4, ligands of DNAM1 and its paired coinhibitory receptor TIGIT, which counterbalanced the cytolytic activities of NK cells. Collectively, our results link the cytolytic immune responses of NK cells to the clearance of SARS-CoV-2 and show that the DNAM1 pathway modulates host-pathogen interactions during SARS-CoV-2 infection.

The necrotrophic pathogen Sclerotinia sclerotiorum is one of the most damaging and economically important plant pathogens. Pydiflumetofen, which was developed by Syngenta Crop Protection, has already been registered in China for the management of Sclerotinia stem rot, which was caused by S. sclerotiorum in oilseed rape. In an attempt to preempt and forestall the development of resistance to this useful fungicide, the current study was initiated to investigate the potential mechanism of resistance in laboratory mutants. Five pydiflumetofen-resistant S. sclerotiorum mutants were successfully generated by repeated exposure to the fungicide under laboratory conditions. Although the mutants had greatly reduced sensitivity to pydiflumetofen, they were also found to have significantly ( P < 0.05) reduced fitness, exhibiting reduced mycelial growth and sclerotia formation on potato dextrose agar medium. However, three of the four mutants had significantly ( P < 0.05) increased pathogenicity on detached soybean leaves compared with their respective parental isolates, indicating a moderate to high level of fungicide resistance risk according to the criteria of the Fungicide Resistance Action Committee. Sequence analysis of four succinate dehydrogenase ( Sdh ) target genes identified several nucleotide changes in the sequences of the pydiflumetofen-resistant mutants, most of which were synonymous and caused no changes to the predicted amino acid sequences. However, all of the pydiflumetofen-resistant mutants had two amino acid point mutations (A11V and V162A) in their predicted SsSdhB sequence. No similar changes were found in the SsSdhA , SsSdhC , and SsSdhD genes of any of the mutants tested. In addition, there was a positive cross-resistance between pydiflumetofen and boscalid, and no cross-resistance between pydiflumetofen and other commonly used fungicides, including tebuconazole, fludioxonil, cyprodinil, dimethachlone, prochloraz, pyraclostrobin, fluazinam, procymidone, and carbendazim. These results indicate that pydiflumetofen has great potential as an alternative fungicide for the control of S. sclerotiorum , especially where resistance to other fungicides has already emerged. Mixing or alternate application with fludioxonil, prochloraz, and fluazinam could be used to limit the risk of resistance to pydiflumetofen.

miR-200c is a tumor suppressor miRNA that plays a critical role in regulating epithelial phenotype and cancer stemness. p53 deficiency downregulates the expression of miR-200c and leads to epithelial-mesenchymal transition (EMT) and stemness phenotype, which contributes to the progression of breast cancers. In this study, we demonstrated that CRISPR-mediated knockout (KO) of miR-200c induces metabolic features similar to the metabolic rewiring caused by p53 hot-spot mutations, and that impairing this metabolic reprogramming interferes with miR-200c deficiency-induced stemness and transformation. Moreover, restoring miR-200c expression compromised EMT, stem-cell properties, and the Warburg effect caused by p53 mutations, suggesting that mutant p53 (MTp53) induces EMT-associated phenotypes and metabolic reprogramming by downregulating miR-200c. Mechanistically, decreased expression of PCK2 was observed in miR-200c- and p53-deficient mammary epithelial cells, and forced expression of miR-200c restored PCK2 in p53 mutant-expressing cells. Reduced PCK2 expression not only led to attenuated oxidative phosphorylation (OXPHOS) and increased stemness in normal mammary epithelial cells but also compromised the enhanced OXPHOS and suppression of cancer stemness exerted by miR-200c in p53 mutation-bearing basal-like breast cancer (BLBC) cells. Clinically, PCK2 expression is negatively associated with EMT markers and is downregulated in basal-like subtype and cases with low miR-200c expression or p53 mutation. Notably, low expression of PCK2 is associated with poor overall survival (OS) in patients with breast cancer. IMPLICATIONS: Together, our results suggest that p53 and miR-200c regulate OXPHOS and stem/cancer stemness through PCK2, and loss of the p53-miR-200c-PCK2 axis might provide metabolic advantages that facilitate cancer stemness, leading to the progression of BLBCs., (©2021 American Association for Cancer Research.)

Apical lesions, the general term for chronic infectious diseases, are very common dental diseases in modern life, and are caused by various factors. The current prevailing endodontic treatment makes use of X-ray photography taken from patients where the lesion area is marked manually, which is therefore time consuming. Additionally, for some images the significant details might not be recognizable due to the different shooting angles or doses. To make the diagnosis process shorter and efficient, repetitive tasks should be performed automatically to allow the dentists to focus more on the technical and medical diagnosis, such as treatment, tooth cleaning, or medical communication. To realize the automatic diagnosis, this article proposes and establishes a lesion area analysis model based on convolutional neural networks (CNN). For establishing a standardized database for clinical application, the Institutional Review Board (IRB) with application number 202002030B0 has been approved with the database established by dentists who provided the practical clinical data. In this study, the image data is preprocessed by a Gaussian high-pass filter. Then, an iterative thresholding is applied to slice the X-ray image into several individual tooth sample images. The collection of individual tooth images that comprises the image database are used as input into the CNN migration learning model for training. Seventy percent (70%) of the image database is used for training and validating the model while the remaining 30% is used for testing and estimating the accuracy of the model. The practical diagnosis accuracy of the proposed CNN model is 92.5%. The proposed model successfully facilitated the automatic diagnosis of the apical lesion.

Context: Genetic risk factors play a major role in the pathoetiology of autoimmune thyroid diseases (AITD). So far, only common risk variants have been identified in AITD susceptibility genes. Recently, rare genetic variants have emerged as important contributors to complex diseases, and we hypothesized that rare variants play a key role in the genetic susceptibility to AITD., Objective: We aimed to identify new rare variants that are associated with familial AITD., Methods: We performed deep sequencing of 3 previously mapped AITD-linked loci (10q, 12q, and 14q) in a dataset of 34 families in which AITD clustered (familial AITD)., Results: We identified 13 rare variants, located in the inositol polyphosphate multikinase (IPMK) gene, that were associated with AITD (ie, both Graves' disease [GD] and Hashimoto's thyroiditis [HT]); 2 rare variants, within the dihydrolipoamide S-succinyltransferase (DLST) and zinc-finger FYVE domain-containing protein (ZFYVE1) genes, that were associated with GD only; and 3 rare variants, within the phosphoglycerate mutase 1 pseudogene 5 (PGAM1P5), LOC105369879, and methionine aminopeptidase 2 (METAP2) genes, that were associated with HT only., Conclusion: Our study demonstrates that, in addition to common variants, rare variants also contribute to the genetic susceptibility to AITD. We identified new rare variants in 6 AITD susceptibility genes that predispose to familial AITD. Of these, 3 genes, IPMK, ZFYVE1, and METAP2, are mechanistically involved in immune pathways and have been previously shown to be associated with autoimmunity. These genes predispose to thyroid autoimmunity and may serve as potential therapeutic targets in the future., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This review paper aims to identify the main sources of carbon dioxide (CO 2 ) emissions from wastewater treatment plants (WWTPs) and highlights the technologies developed for CO 2 capture in this milieu. CO 2 is emitted in all the operational units of conventional WWTPs and even after the disposal of treated effluents and sludges. CO 2 emissions from wastewater can be captured or mitigated by several technologies such as the production of biochar from sludge, the application of constructed wetlands (CWs), the treatment of wastewater in microbial electrochemical processes (microbial electrosynthesis, MES; microbial electrolytic carbon capture, MECC; in microbial carbon capture, MCC), and via microalgal cultivation. Sludge-to-biochar and CW systems showed a high cost-effectiveness in the capture of CO 2 , while MES, MECC, MCC technologies, and microalgal cultivation offered efficient capture of CO 2 with associate production of value-added by-products. At the state-of-the-art, these technologies, utilized for carbon capture and utilization from wastewater, require more research for further configuration, development and cost-effectiveness. Moreover, the integration of these technologies has a potential internal rate of return (IRR) that could equate the operation or provide additional revenue to wastewater management. In the context of circular economy, these carbon capture technologies will pave the way for new sustainable concepts of WWTPs, as an essential element for the mitigation of climate change fostering the transition to a decarbonised economy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

This prospective study aimed to investigate the clinical and microbiological characteristics of different Aeromonas species. Clinical isolates of Aeromonas species between 2016 to 2018 were collected in a university hospital in southern Taiwan. The species was determined by rpoD or gyrB sequencing. A total of 222 Aeromonas isolates from 160 patients in 164 episodes were identified. The crude in-hospital mortality was 17.2%. The most frequently isolated species was Aeromonas veronii (30.6%), followed by A. caviae (24.8%), A. hydrophila (23%), and A. dhakensis (16.7%). The major clinical manifestations were primary bacteremia (31.1%), skin and soft tissue infection (22.6%), and biliary tract infection (18.3%). The most common underlying diseases were malignancy (45.1%), diabetes mellitus (27.4%), and liver cirrhosis or chronic hepatitis (26.2%). A. hydrophila and A. dhakensis predominated in the skin and soft tissue infection (p<0.0001), whereas A. vernoii and A. caviae prevailed in primary bacteremia and biliary tract infections (p=0.012). Pneumonia, malignancy, and ascF-ascG genotype were independent factors associated with mortality. Ertapenem susceptibility was decreased in A. sobria (42.9%), A. veronii (66.7%), A. dhakensis (73%), and A. hydrophila (84.3%). Cefotaxime resistance was found in 30.9% of A. caviae and 18.9% of A. dhakensis isolates, much more prevalent than the other species. The metallo-β-lactamase bla CphA was almost invariably present in A. dhakensis , A. hydrophila , and A. veronii (100%, 100% and 89.9%, respectively). Amp-C β-lactamases such as bla MOX and bla AQU-1 were identified in all A. caviae and 91.9% of A. dhakensis isolates. Cefepime, fluoroquinolones and tigecycline showed good in vitro activity against aeromonads., 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 © 2021 Chen, Su, Li, Tsai, Lo, Syue, Li, Lee, Lee, Ko and Chen.)

SARS-CoV-2 exploits the host cellular machinery for virus replication leading to the acute syndrome of coronavirus disease 2019 (COVID-19). Growing evidence suggests SARS-CoV-2 also exacerbates many chronic diseases, including cancers. As mutations on the spike protein (S) emerged as dominant variants that reduce vaccine efficacy, little is known about the relation between SARS-CoV-2 virus variants and cancers. Compared to the SARS-CoV-2 wild-type, the Gamma variant contains two additional NXT/S glycosylation motifs on the S protein. The hyperglycosylated S of Gamma variant is more stable, resulting in more significant epithelial-mesenchymal transition (EMT) potential. SARS-CoV-2 infection promoted NF-κB signaling activation and p65 nuclear translocation, inducing Snail expression. Pharmacologic inhibition of NF-κB activity by nature food compound, I3C suppressed viral replication and Gamma variant-mediated breast cancer metastasis, indicating that NF-κB inhibition can reduce chronic disease in COVID-19 patients. Our study revealed that the Gamma variant of SARS-CoV-2 activates NF-κB and, in turn, triggers the pro-survival function for cancer progression., Competing Interests: None., (AJCR Copyright © 2021.)

Purpose: To analyze the characteristics of clinical trials of mucosal melanoma (MM) based on WHO international clinical trial registration platform (ICTRP), in order to provide a reference for clinical translational research of mucosal melanoma., Methods: WHO ICTRP database were searched to collect MM-related clinical trials. Two reviewers independently screened items, extracted data, and descriptive analysis was performed for the included trials, including number of registrations, research phase, country/region, clinical study design, etc. RESULTS: The results showed that there were 51 registered clinical trials involving MM. European and American countries and East Asia were the main study sites, and head and neck MM were mainly investigated in East Asia (11/12). Forty-eight of them were sponsored by investigators, and only 3 were sponsored by biomedical companies. The main clinical trials were single center (42 items) and in stage II (38 items). Interventions were complex, and multiple treatments and drug therapy accounted a dominant position., Conclusions: In-depth analysis of clinical trials information can help to understand the current situation and development trends in the field of mucosal melanoma. The number of clinical studies of mucosal melanoma is relatively small and has not received much attention.

T-cell reduction is an important characteristic of coronavirus disease 2019 (COVID-19), and its immunopathology is a subject of debate. It may be due to the direct effect of the virus on T-cell exhaustion or indirectly due to T cells redistributing to the lungs. HIV/AIDS naturally served as a T-cell exhaustion disease model for recognizing how the immune system works in the course of COVID-19. In this study, we collected the clinical charts, T-lymphocyte analysis, and chest CT of HIV patients with laboratory-confirmed COVID-19 infection who were admitted to Jin Yin-tan Hospital (Wuhan, China). The median age of the 21 patients was 47 years [interquartile range (IQR) = 40-50 years] and the median CD4 T-cell count was 183 cells/μl (IQR = 96-289 cells/μl). Eleven HIV patients were in the non-AIDS stage and 10 were in the AIDS stage. Nine patients received antiretroviral treatment (ART) and 12 patients did not receive any treatment. Compared to the reported mortality rate (nearly 4%-10%) and severity rate (up to 20%-40%) among COVID-19 patients in hospital, a benign duration with 0% severity and mortality rates was shown by 21 HIV/AIDS patients. The severity rates of COVID-19 were comparable between non-AIDS (median CD4 = 287 cells/μl) and AIDS (median CD4 = 97 cells/μl) patients, despite some of the AIDS patients having baseline lung injury stimulated by HIV: 7 patients (33%) were mild (five in the non-AIDS group and two in the AIDS group) and 14 patients (67%) were moderate (six in the non-AIDS group and eight in the AIDS group). More importantly, we found that a reduction in T-cell number positively correlates with the serum levels of interleukin 6 (IL-6) and C-reactive protein (CRP), which is contrary to the reported findings on the immune response of COVID-19 patients (lower CD4 T-cell counts with higher levels of IL-6 and CRP). In HIV/AIDS, a compromised immune system with lower CD4 T-cell counts might waive the clinical symptoms and inflammatory responses, which suggests lymphocyte redistribution as an immunopathology leading to lymphopenia in COVID-19., 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 © 2021 Lin, Lin, Wang, Wen, Xiang, Fan, Li, Wu, Lin, Lin, Sun, Chen, Chen, Lian, Xie, Lin, Xie, Li, Peng, Wang, Lin, Chen, Huang and Fu.)