Previous work demonstrated that arginine is one of the strongest insulin secretagogues. However, knowledge of the mechanisms linking chronic arginine metabolism with β-cell function and insulin secretion is relatively limited. After preliminary selection of concentration according to the cell proliferation, the MIN6 pancreatic β-cells were randomly assigned to culture in 0.04 mM (low-arginine, LA), 0.4 mM (standard-arginine, SA), or 8 mM arginine (high-arginine, HA) for 24 h. Following the treatment, a combination of transcriptomics and metabolomics, together with a series of molecular biological tests were performed to investigate the responses of β-cells to varied arginine availability. Our results showed that HA treatment reduced the chronic insulin releases, and LA and HA treatments decreased the glucose-stimulated insulin secretions (GSIS) of β-cells relative to the SA group (p < .05). Transcriptomics analysis indicated that LA administration significantly inhibited oxidative phosphorylation and ATP metabolic process but promoted DNA repair and mRNA processing in β-cells, while HA administration affected ammonium ion metabolic process and mRNA export (p < .05). Both LA and HA regulated the expressions of genes involved in DNA replication, cell-cycle phase transition, and response to oxidative stress (p < .05). Protein-protein interaction and transcription factor analyses suggested that Trp53 and Nr4a2 genes may play key roles during arginine stimulation. On the contrary, metabolomics analysis demonstrated that the differentially expressed metabolites (DEM) of MIN6 β-cells induced by LA were mainly enriched in glycerophospholipid metabolism, linoleic acid metabolism, and purine metabolism, while most DEMs between LA vs. SA comparison belonged to amino acid metabolism. When combined the three groups, co-expression analysis suggested that insulin secretions had strong associations with L-pyroglutamic acid, L-glutamate, and creatine concentrations, while intracellular insulin contents were mainly correlated to L-arginine, argininosuccinic acid, and phosphorylcholine. At last, integrated analysis of transcriptomics and metabolomics showed that glycerophospholipid metabolism, biosynthesis of unsaturated fatty acids, and amino acid metabolism were the most relevant pathways in β-cells exposed to abnormal arginine supply. This descriptive bioinformatics analysis suggested that the disturbed carbohydrate, lipid, and amino acid metabolisms, as well as the increased apoptosis and elevated oxidative stress, contributed to the reduced insulin secretion and lower GSIS in β-cells induced by LA or HA treatments, while some underlying mechanisms need to be further explored.

Keywords: MIN6 β-cell; arginine availability; functional integrity; glucose-stimulated insulin secretion; insulin release; metabolomics; transcriptomics.

Objectives: Barleria, a large genus of the Acanthaceae family, comprises more than 300 species with diverse taxonomy, cytogenetics, phytochemistry and pharmacological potential. Therefore, the aim of this review is to critically assess the research on Barleria and provide guidance for future investigations.

Methods: The data were obtained from different sources, such as books, theses, journals and some of the websites and internet-based searches, published from 1901 to 2020. Data obtained from PubMed, Google Scholar, ScienceDirect, online electronic journals, SpringerLink, Wiley, etc. have also been used.

Key findings: The species of this genus exhibit considerable medicinal properties. Cytogenetical data are scantily available with chromosome counts available for only 24 species. The most common chromosome number is 2n = 2x = 40. So far, 187 compounds are reported from Barleria species. The active principles, their uses, toxicity and pharmacological effects are discussed. Essential oils, flavones, flavonoids, glycosides, terpenes and terpenoids form the major compounds.

Summary: It is highly recommended that the pharmacological and economic potential of Barleria species should be exploited and more detailed studies and attention be geared towards its utilization and conservation. In addition, to ensure maximum pharmacological benefits and sustainable use, it is necessary to have empirical information explaining its ethnobotanical values as well as commercial potential.

Keywords: chemistry; chromosomes; ethnomedicine; pharmacology; taxonomy.

Extensive nutrient loss is one of the most challenging issues faced by agricultural production regions worldwide. However, diffuse pollution in the subtropical mountainous watersheds is rarely simulated. A watershed model with regional parameter values is essential for watershed management. In this study, SWAT, one of the most popular models was applied to simulate daily discharge (years of 2008-2014), NO₃-N flux (2012-2014), and tea yield (2012-2014) in the Ping-Lin watershed (PLW) of Taiwan, as well as to test the effectiveness of a modified fertilization strategy. The results demonstrated that SWAT was capable of simulating daily discharge variation, daily riverine NO₃-N flux, and tea yield in the PLW. NO₃-N yield of the tea farm (47 kg/ha/yr) was 9 times higher than that of the forest (5.1 kg/ha/yr). A significant proportion (~ 50%) of the input nitrogen (including dry/wet deposition and fertilizer) infiltrated into the soil, resulting in a poor fertilizer uptake efficiency of the tea tree. It was demonstrated that the modified fertilization strategy (apply fertilizer in small rainfall event, i.e., daily rainfall < 20 mm/day, and not in a single day) could increase the nitrogen uptake and harvest yield of the tea tree by 14% and 4%, respectively, with a 10% reduction in nitrogen input. Furthermore, this strategy significantly reduced the nitrogen yields from surface flow (75%), lateral flow (36%), percolation (50%), and groundwater (48%). A popular model with verified parameter values could help in developing a win-win strategy for both farmers and regulators, thus realizing the goals of sustainable agricultural practices.

Keywords: Diffuse pollution; Fertilization strategy; Nitrate flux; Sustainable agricultural practices; Taiwan.

Despite being effective for many other solid tumors, traditional anti-angiogenic therapy has been shown to be insufficient for the treatment of malignant glioma. Here, we report the development of polyphenol nanoparticles (NPs), which not only inhibit the formation of new vessels but also enable targeted disruption of the existing tumor vasculature. The NPs are synthesized through a combinatory iron-coordination and polymer-stabilization approach, which allows for high drug loading and intrinsic tumor vessel targeting. We study a lead NP consisting of quercetin and find that the NP after intravenous administration preferentially binds to VEGFR2, which is overexpressed in tumor vasculature. We demonstrate that the binding is mediated by quercetin, and the interaction of NPs with VEGFR2 leads to disruption of the existing tumor vasculature and inhibition of new vessel development. As a result, systemic treatment with the NPs effectively inhibits tumor growth and increases drug delivery to tumors.

Background: Hand eczema (HE) is a common disorder that negatively impacts the quality of life. During the COVID-19 pandemic, several studies have shown an increase in HE in health care workers. However, data on the general population are lacking.

Objective: To assess the prevalence and risk factors of HE among the Saudi general population during the pandemic.

Methods: This cross-sectional study was conducted using an online questionnaire composed of 4 sections (participant characteristics, history of atopic disorders, hand hygiene methods, and HE symptoms). It was distributed on Twitter during the lockdown period, between August 2020 and September 2020. Descriptive, bivariate, and multivariable analyses were conducted using STATA v16.

Results: A total of 582 (52.6% women and 47.4% men) participants responded to the questionnaire. The 6-month prevalence of HE was 34%. In multivariable analysis, having a past history of eczema, rhinitis/conjunctivitis, using soaps for >5 times daily, using gloves daily, and using moisturizers were significantly associated with HE. Interestingly, using sanitizers for >5 times daily was not a statistically significant risk factor.

Limitations: Due to its internet-based nature, the response rate cannot be accurately calculated. In addition, the response bias and the small sample size limit the generalizability of the results and prevent drawing broad conclusions and accurate measurement of prevalence.

Conclusion: HE prevalence increased during the pandemic in the Saudi general population. Frequent use of soaps and gloves, but not sanitizers, increased HE risk.

Keywords: CI, confidence interval; COVID-19; HE, hand eczema; OR, odds ratio; contact dermatitis; eczema; hand eczema; hand hygiene; skin barrier.

We describe the case of a 14-year-old boy hospitalized for multisystem inflammatory syndrome in children who developed atrial fibrillation during the acute phase and a transient Brugada type 1 pattern in the subacute phase. Eight months later, a provocative test with ajmaline confirmed the suspicion of Brugada syndrome. (Level of Difficulty: Intermediate.).

Keywords: BP, Brugada phenocopy; BrS, Brugada syndrome; Brugada phenocopy; Brugada syndrome; ECG, electrocardiographic; MIS-C, multisystem inflammatory syndrome in children; MPL, modified precordial lead; SARS-CoV-2, severe acute respiratory syndrome-coronavirus-2; autonomic system dysregulation; cytokine storm; multisystem inflammatory syndrome in children.

Peripheral neuropathy, which is a complication of diabetes mellitus (DM), is thought to occur in the pre-DM state, being known as impaired glucose tolerance (IGT) neuropathy, although its pathogenesis is unknown. Since it is reversible, an effective treatment at the pre-DM stage could stop the progression of peripheral neuropathy and improve patients' quality of life and reduce medical costs. We investigated the hypersensitivity to mechanical and thermal stimuli during the pre-DM state in Tsumura Suzuki Obese Diabetes (TSOD) mice, a type 2 DM mouse model. The expression pattern of the Transient Receptor Potential Vanilloid 1 (TRPV1)-positive cells in the dorsal root ganglia (DRG) was examined in TSOD mice, which showed a pre-DM state at 5-12 weeks of age and decreased mechanical and thermal nociceptive thresholds. Additionally, the size of TRPV1-positive cells in TSOD mice increased compared with that in non-diabetic controls (Tsumura Suzuki Non-Obesity; TSNO). Furthermore, the expression of TRPV1 on myelinated nerve fibers (neurofilament heavy-positive cells) had significantly increased. Thus, TSOD mice in the pre-DM state at 5-12 weeks of age could be a useful animal model of IGT neuropathy. We also hypothesized that the development of IGT neuropathy may involve a switch in TRPV1 expression from small, unmyelinated neurons to large, myelinated neurons in the DRG.

Keywords: ANOVA, Analysis of variance; DM, diabetes mellitus; DRG, dorsal root ganglion; Diabetes mellitus; FITC, fluorescein isothiocyanate; HFD, High-Fat Diet; IGT, impaired glucose tolerance; ITT, insulin tolerance test; Impaired glucose tolerance; LPA, Lysophosphatidic Acid; Mechanical allodynia; NF-H, neurofilament heavy; STZ, streptozotocin; TRITC, tetramethylrhodamine; TRPV1, Transient Receptor Potential Vanilloid 1; TSNO, Tsumura Suzuki Non-Obesity; TSOD, Tsumura Suzuki Obese Diabetes; Thermal hypersensitivity; ir, immunoreactive; tHODE, total Hydroxyoctadecadienoic Acid.

Introduction: EGFR exon 20 insertions (EGFRex20ins) are a diverse set of mutations in NSCLC that are refractory to tyrosine kinase inhibitors. We describe real-world EGFRex20ins detection patterns in patients with advanced NSCLC in the United States.

Methods: Data from 2011 to 2020 were extracted from the Flatiron Health electronic health record-derived deidentified database.

Results: Among 67,281 patients with advanced NSCLC and at least two clinic visits, 66.8% were tested for EGFR mutations, of whom 13.9% tested positive. Of these, 4.9% had EGFRex20ins. The median time from NSCLC diagnosis to the first positive EGFRex20ins test result was 23 days, including 9 days of laboratory testing time. The EGFRex20ins were reported in 0.6% to 1.0% of all patients with advanced NSCLC and account for 3.9% to 5.3% of all EGFR mutations. During the study period, reverse transcription-polymerase chain reaction testing rates decreased whereas next-generation sequencing rates increased both in overall and among patients with tumors positive for EGFRex20ins. Tissue was the most common sample type used for EGFR and EGFRexon20ins detection (81.1% and 84.9%, respectively), whereas blood sampling for EGFRexon20ins detection increased from 0% (2011) to 37.2% (2020). For 23.7% of patients with EGFRex20ins, treatment was initiated before receiving the first positive EGFRex20ins test result, with therapies including immuno-oncology agents as the most common treatment type from 2017 to 2020.

Conclusions: EGFR testing and detection of EGFRex20ins in patients with NSCLC have increased slightly over time with the increasing use of next-generation sequencing. The current late-stage development of EGFRex20ins-targeted therapy is driving a need for more efficient testing.

Keywords: EGFR exon 20 insertions; Epidermal growth factor receptor; Next-generation sequencing; Non–small cell lung cancer; Testing rates; Tyrosine kinase inhibitor therapy.

Objective: To describe the local experience of adult patients presenting with cannabinoid hyperemesis syndrome (CHS) to an urban ED in the outer northern suburbs of Melbourne.

Methods: Retrospective chart review of adult patients presenting to the ED with a documented history of CHS or equivalent terminology from January 2015 to January 2021. Age, sex, cannabis use, clinical features, pathology results, imaging and symptomatic management were examined as well as outcomes regarding disposition, representation, morbidity and mortality.

Results: One hundred and forty-two adult presentations were included. Sixty-seven were unique presentations and 29 were patients who represented during the study period. Most represented within 3 months (37.8%) and most represented at least twice. Males were overrepresented (68.7%). Patients were young (median age 31 years, interquartile range 23-35 years) and all had a history of regular cannabis use (usually daily). Cyclical nausea and/or vomiting was the most common clinical feature compared to others in previously reported diagnostic criteria. Patients typically had elevated white cell counts with associated neutrophilia (75.8%) and mild hypokalaemia (57.9%). Lipase was not elevated, and C-reactive protein was typically less than 50 mmol/L (98.2%). Imaging was not commonly performed but largely normal. Treatment was supportive with anti-emetic use, intravenous fluids and analgesia. There were no deaths or admissions to intensive care.

Conclusions: Cyclical nausea and vomiting was the most common feature observed in this cohort compared to other clinical features reported in prior studies. Serum lipase was normal and C-reactive protein only mildly elevated. Prospective studies are required to further assess these findings.

Keywords: cannabinoid; cannabis; case series; hyperemesis; vomiting.

Background: A questionnaire survey was conducted to assess the implementation status of geriatric assessment in cancer treatment and the potential for collaboration between medical care and the long-term care insurance system.

Methods: Questionnaires were sent to 795 facilities in Japan. The questions were instructed to be answered via an online survey (SurveyMonkey®), which began in September 2020 and closed on 31 October 2020. The questionnaire consisted of 8 questions on the status of geriatric assessment implementation and 15 questions on the long-term care insurance system.

Results: In total, 631 departments in 340 (42.8%) of 795 hospitals and clinics provided responses. Approximately 81.5% of the departments did not perform geriatric assessment. The common reasons were lack of knowledge about geriatric assessment (54.0%) and lack of personnel (35.5%). Even if geriatric assessment was conducted, 63.6% of departments did not utilize geriatric assessment results in clinical practice. Approximately 61.7% of respondents were familiar with the long-term care insurance system and 62.9% with the certification process. Moreover, 28% of respondents used certification examination results in treatment planning.

Conclusions: Geriatric assessment is less recognized than the long-term care insurance system, and its results are rarely used in clinical practice. However, 28% of certification examination results are utilized in treatment decision-making. Notably, this survey first showed the incorporation of the long-term care insurance system into the medical care of vulnerable elderly patients with cancer.

Keywords: elderly cancer patients; geriatric assessment; long-term care insurance.

Here, we present a comprehensive protocol for the generation and functional characterization of chimeric antigen receptor (CAR) T cells and their products by mass cytometry in a reproducible and scalable manner. We describe the production of CAR T cells from human peripheral blood mononuclear cells. We then detail a three-step staining protocol with metal-labeled antibodies and the subsequent mass cytometry analysis. This protocol allows simultaneous characterization of CAR T cell intracellular signaling, activation, proliferation, cytokine production, and phenotype in a single assay.

Keywords: Cell Biology; Cell culture; Cell isolation; Flow Cytometry/Mass Cytometry; Health Sciences; Immunology; Single Cell.

Keywords: Bulkamid®; intrinsic sphincter deficiency; polyacrylamide hydrogel; stress urinary incontinence; women.

Background: Causes of extrahepatic portal vein obstruction include abdominal surgeries such as pancreaticoduodenectomy. We improved jejunal variceal bleeding due to extrahepatic portal vein occlusion after pancreaticoduodenectomy, by shunting of the testicular vein.

Case presentation: A 72-year-old man was diagnosed with extrahepatic bile duct cancer and underwent subtotal stomach-preserving pancreaticoduodenectomy 5 years ago. No postoperative complications occurred, adjuvant chemotherapy using gemcitabine hydrochloride was performed, and the patient remained recurrence-free. One year and 6 months post-operation, extrahepatic portal vein stenosis appeared, but no recurrence was noted. However, 4 years and 6 months later, recurrent gastrointestinal bleeding occurred, and the patient was diagnosed with an extrahepatic portal vein obstruction. Double-balloon enteroscopy showed capillary dilatation and varicose veins in the hepaticojejunostomy region, and venous bleeding from collateral blood vessels was diagnosed. A superior mesenteric vein to the right testicular vein shunt operation was performed, following which the gastrointestinal bleeding disappeared, and the anemia improved. Although transient hepatic encephalopathy occurred, conservative treatment relieved it. Double-balloon enteroscopy confirmed the disappearance of abnormal blood vessels.

Conclusions: A portosystemic shunt operation using the right testicular vein effectively relieved refractory variceal bleeding around the hepaticojejunostomy site in the jejunum due to an extrahepatic portal vein obstruction after pancreaticoduodenectomy.

Keywords: Pancreaticoduodenectomy; Portal vein obstruction; Shunt operation; Testicular vein; Variceal bleeding.

Peripheral nerve injury usually impairs neurological functions. The excessive oxidative stress and disrupted bioelectrical conduction gives rise to a hostile microenvironment and impedes nerve regeneration. Therefore, it is of urgent need to develop tissue engineering products which help alleviate the oxidative insults and restore bioelectrical signals. Melatonin (MLT) is an important endogenous hormone that diminishes the accumulation of reactive oxygen species. Reduced graphene oxide (RGO) possesses the excellent electrical conductivity and biocompatibility. In this study, a multilayered MLT/RGO/Polycaprolactone (PCL) composite scaffold was fabricated with beaded nanostructures to improve cell attachment and proliferation. It also exhibited stable mechanical properties by high elastic modulus and guaranteed structural integrity for nerve regeneration. The live/dead cell staining and cell counting kit assay were performed to evaluate the toxicity of the scaffold. JC-1 staining was carried out to assess the mitochondrial potential. The composite scaffold provided a biocompatible interface for cell viability and improved ATP production for energy supply. The scaffold improved the sensory and locomotor function recovery by walking track analysis and electrophysiological evaluation, reduced Schwann cell apoptosis and increased its proliferation. It further stimulated myelination and axonal outgrowth by enhancing S100β, myelin basic protein, β3-tubulin, and GAP43 levels. The findings demonstrated functional and morphological recovery by this biomimetic scaffold and indicated its potential for translational application.

Keywords: Melatonin; Nerve guide conduit; Peripheral nerve injury; Reduced graphene oxide; Tissue engineering.

Lipid metabolites, beyond triglycerides and cholesterol, have been shown to have vast potential for applications in clinical applications, with substantial societal and economical value. To successfully evolve from the current research-grade methods to assays suitable for routine clinical applications, a harmonization - if not standardization - of these mass spectrometry-based workflows is necessary. Input on clinical needs and technological capabilities must be obtained from all relevant stakeholders, including wet lab scientists, informaticians and data scientists, manufacturers, and medical professionals. In order to build bridges between this diverse group of professionals, the International Lipidomics Society and its Clinical Lipidomics Interest Group were created. This opinion article is intended to provide an overview of international efforts to tackle the issues of workflow harmonization, and to serve as an open invitation for others to join this growing community.

Keywords: Harmonization; Lipidomics; Standardization; Translation; Validation.

We use a suite of cutting-edge natural language processing methods to quantify and characterize societal and gender biases in popular movie content. Our data set consists of English subtitles of popular movies from Bollywood-the Mumbai film industry-spanning 7 decades (700 movies). In addition, we include movies from Hollywood and movies nominated for the Academy Awards for contrastive purposes. Our findings indicate that while the overall portrayal of women has improved over time in popular movie dialogues from both Bollywood and Hollywood, modern films still exhibit considerable gender bias and are yet to achieve equal representation among genders. We also observe a strong bias favoring fair skin color in Bollywood content that occurred consistently across all time periods we considered. While our geographic representation analysis indicates improved inclusion over time for several Indian states, it also reveals a long-standing under-representation of many northeastern Indian states.

Keywords: Bollywood; Hollywood; gender bias; social bias.

The fabrication and applications of superhydrophobic surfaces (contact angle >150°, sliding angle <10°) have attracted worldwide interest with respect to materials and devices. In this work, the laser-induced graphene (LIG) superhydrophobic surface transition from pinning to rolling via an extremely simple solvent treatment of LIG in air is reported. By adding a certain solvent (e.g., ethanol) to the surface, the LIG superhydrophobic surface changes from pinning (sliding angle = 180°) to rolling (sliding angle <6°), which is attributed to the chemically changed surface properties and surface morphology of LIG. Three applications are demonstrated with the developed superhydrophobic LIG, including surface-enhanced Raman spectroscopy, water-oil separation, and anti-icing.

Keywords: analyte enrichment; laser-induced graphene; pinning to rolling; superhydrophobic surfaces; water/oil separation.

A strategy to access diverse multisubstituted acrylamides from cyclic ketones is realized via palladium/norbornene-catalyzed α-carbamoylation and ipso-functionalization of the corresponding enol triflates. The development of bulky C2 secondary amide-substituted norbornene cocatalysts is the key to achieve the desired reactivity and selectivity. Readily available carbamoyl chlorides serve as effective electrophiles; various moieties including alkenyl, hydrogen, alkynyl, aryl, and alkyl groups can be installed at the ipso position. In addition, tandem α-carbamoylation/ipso-annulations are demonstrated to furnish lactam-containing polycyclic scaffolds. The utility of this method is exemplified in the streamlined preparation of a platelet-activating factor (PAF)-antagonist.

Keywords: Acrylamides; Carbamoylation; C−H functionalization; Norbornene; palladium.