Background and Purpose: Berberine, a natural isoquinoline alkaloid, exhibits a variety of pharmacological effects but the pharmacological targets and mechanisms are remained elusive. Here, we report a novel finding that berberine inhibits acetylcholine (ACh)-induced Ca2+ oscillations which may underlie the pathogenesis of the L-arginine-induced mouse model of acute pancreatitis (AP). Experimental approach: Patch-clamp recordings and confocal Ca2+ imaging were applied in acute dissociated pancreatic acinar cells prepared from CD1 mice to examine the effects of berberine on ACh-induced Ca2+ oscillations. The L-arginine-induced acute pancreatitis mouse model was used to evaluate the protective effects of berberine against pathological changes. Key Results: Whole-cell patch-clamp recordings showed that berberine (from 0.1 to 10 µM) reduced ACh-induced Ca2+ oscillations in a concentration-dependent manner, and this inhibition was also depended on ACh concentrations. The inhibitory effect of berberine neither occurred in intracellular targets nor extracellular cholecystokinin (CCK) receptors, chloride (Cl-) channels, and store-operated Ca2+ channels. Together, the results demonstrate that berberine directly inhibits M3 muscarinic receptors, which is further confirmed by the evidence of the interaction between berberine and M3 receptors in acinar cells. In a L-arginine AP model, berberine eliminates the ACh-induced Ca2+ oscillations, the elevation of pancreatic amylase and pulmonary myeloperoxidase, and improves acinar cell pathological injury. Conclusions and Implications: We provide novel evidence that berberine inhibits M3 receptors, in turn eliminates ACh-induced Ca2+ oscillations and L-arginine-enhanced Ca2+ signaling, which underlie the protective effects of berberine on pancreatic acinar cells against pathological changes in an acute pancreatitis model.

Hepatic arteriovenous malformation mostly occurs as a manifestation of hereditary hemorrhagic telangiectasia. Clinical symptoms include hyperpulsatile heart failure, hepatic encephalopathy, and ascites. We present a case of hepatic arteriovenous malformation and atrial septal defect causing heart failure.

Background and Purpose The approved small-molecule inhibitors of anaplastic lymphoma kinase (ALK) have shown remarkable efficacy in some subset of cancer patients. However, the numerous ALK mutants or fusion partners are resistant to such drugs, greatly limiting their application in clinic. Despite the drug design strategy of proteolysis-targeting chimera (PROTAC) holds great potential to overcome drug resistance in theory, there are obvious disadvantages for the reported PROTACs that include high molecular weight, long linkers, difficult synthesis routes as well as insufficient evidence in activity for diverse ALK mutants. Experimental Approach In this study, we synthesized a miniaturized PROTAC of ALK named AP-1 following the principle of minimalist design. Two simple chemical units of ligands and a minimized linker with only two atoms were selected for synthesis of AP-1. Key Results At cellular level, AP-1 successfully degraded three types of ALK mutants including NPM-ALK, EML4-ALK and F1174L mutation ALK form with strong activity, high selectivity in ALK-positive cells. In tumor-bearing mouse models, AP-1 showed the stronger antitumor efficacy than controls as well as the similar compounds reported in literatures. Conclusion and Implications AP-1 with an extremely simple PROTAC structure can be served as an effective candidate drug for therapy of various types of ALK-positive cancers. And the design principle of AP-1 has a good guiding significance for overcoming the disadvantages such as excessive molecular weight and poor solubility of PROTAC.

Primary effusion lymphoma (PEL) is a rare non-Hodgkin lymphoma confined exclusively to body cavities without detectable tumor masses. The term PEL-like is an entity similar to PEL in clinical presentation but without relation to human herpesvirus 8 (HHV8). We report a case of HHV8- and EBV-negative primary effusion-based lymphoma.

Host-parasite interactions can cause strong demographic fluctuations accompanied by selective sweeps of resistance/infectivity alleles. Both demographic bottlenecks and frequent sweeps are expected to reduce the amount of segregating genetic variation and therefore might constrain adaption during coevolution. Recent studies, however, suggest that the interaction of demographic and selective processes is a key component of coevolutionary dynamics and may rather positively affect levels of genetic diversity available for adaptation. Here, we provide direct experimental testing of this hypothesis by disentangling the effect of demography, selection, and of their interaction in an experimental host-parasite system. We grew 12 populations of unicellular algae (Chlorella variabilis) that experienced either growth followed by constant population sizes (3 populations), demographic fluctuations (3 populations), selection induced by exposure to a virus (3 populations), or demographic fluctuations together with virus-induced selection (3 populations). After 50 days, we conducted whole-genome sequencing of each algal population. We observed more genetic diversity in populations that jointly experienced selection and demographic fluctuations than in populations where these processes were experimentally separated. In addition, in those 3 populations that jointly experienced selection and demographic fluctuations, experimentally measured diversity exceeds expected values of diversity that account for the cultures’ population sizes. Our results suggest that eco-evolutionary feedbacks can positively affect genetic diversity and provide the necessary empirical measures to guide further improvements of theoretical models of adaptation during host-parasite coevolution.

We present the case of a 75-year-old female patient was misdiagnosed as thyroid tumor, but was changed to cervical esophageal diverticulum by cervical enhancement CT before the operation.

The detection of leakage in fluorescence angiography (FA) could delay the diagnosis of retinal detachments (RDs). We reported a case of RD in a seven-year-old boy with positive leakage on FA which confused the presentation. A thorough contact lens examination and scleral indentation are mandatory to reach the diagnosis easily.

Background : To determine preoperative Geriatric 8 (G8) score in predicting postoperative complications for elderly head and neck cancer patients . Material and Methods: The prospective study in elderly head and neck cancer patients who underwent surgery during December 2020- June 2022 . G8 score were collected before surgery and analysed for the association with complication outcome. Result : Of 104 patients included in this study ,The mean age was 68.84±6.99 years .The Geriatric 8 (G8)score < 14 which were frail group in 73 cases (70.2%) The Clavien-Dindo complications grade III-IV were 30 patients (28.8%). Among these groups ,26 patients (86.7%) was in frail groups and 4 patients (13.3%) with non frail group which is statistically significant different (p=0.019) and Odd ratio of 3.32 , CI =1.01-10.87, p=0.048 Conclusion : The G8 score is a practical tool for prediction post operative complication in elderly Head and Neck Cancer surgery . Keyword : Geriatric 8 score , Geriatric Head and neck cancer , post operative complication

Non-Hodgkin lymphomas (NHLs) are a heterogeneous group of malignancies originating from the lymphoid tissues, which can be differentiated by distinct epidemiology, etiology, and clinical characteristics. They can occur in the lymph nodes or as extranodal lesions. The vast majority of extranodal oral NHLs are classified as diffuse large B-cell lymphomas (DLBCL). They are usually found in the maxilla and they rarely occur in the mandible. The aim of this paper was to report a case of NHL with mandibular location by detailing its different clinical, radiological, and histopathological aspects. Herein, we report a case of NHL in the under chin region of the mandible in a 66-year-old male patient. The first diagnosis was post-extraction complication with delayed bone healing. The clinical and standard radiological examinations had no pathognomonic features. However, left labio-chin hypoesthesia and CT examination revealed a malignancy of the lesion without any precision. After performing further diagnostic examinations, including a subsequent biopsy, diagnosis of diffuse large B-cell lymphoma (DLBCL) was made. The patient was therefore treated with chemotherapy and he showed a satisfactory outcome for more than 5 years. Intraoral lymphomas may mimic odontogenic lesions; hence it is important for the dentist to be aware of the various manifestations of NHL to avoid delay and inappropriate treatment strategies.

Since H63D syndrome was first described, the authors of this paper systematically investigated for the first time to what extent the adrenal glands, as an integral part of the HPA and SAM axes, are also affected by damage caused by non-transferrin bound iron (NTBI), a hallmark of H63D syndrome. Due to the rarity of the H63D syndrome, the representatives of a number of institutions that regularly deal with the topic in the context of their clinical and research activities have come together for this purpose. Thus, a small but significant amount of patient data could be collected worldwide, analyzed and evaluated, with surprisingly clear pathological results. A secondary aspect is that after reviewing the currently available literature, the team of authors came to the conclusion that the issue of HPA and SAM axes dysfunctions and adrenal synthesis activity seems to be also more frequent in other iron metabolic disorders than it is addressed to in everyday’s clinical practice. The result of this work is a warning call to closely monitor the catecholamine balance, the synthesis and control of all "stress hormones", the condition of the adrenal glands as well as other axis structures very early in the course of the H63D syndrome, in order to make unnecessary organ damages at least a little less likely, if not to prevent it to a large extent if detected early.In the meantime, this work has undergone peer review under the auspices of Swabian Research. In some instances, however, the repository in which it is deposited has not implemented this important change in status, and this note is therefore being provided for clarification.

The quest for alternative building materials, easy availability with supply in an economy where the population increases at high rate in a steady flow per year. Bamboo as a renewable, sustainable alternative material is explored for the production of roofing tiles, Bambusa vulgaris were chipped into flakes, sieve and further subjected to modified conventional treatment, the flake were oven dry in a control temperature of 170 o C to Moisture Content range of 11-12 %, Portland cement were employed as a binder, using batch method of mixing in the production of the roofing tiles. Moisture content, density of the roofing tiles, thickness swelling and impact test were determined, the average moisture content of the tiles12.7%, average density 0.031g/cm 3 , average thickness swelling which showcases the dimensional stability of the tiles is 0.75%. The impact test is 2.6N/mm 2. The various results obtained were favourable suggesting that bamboo most especially of the Bambusa vulgaris can be suitable raw material and substitute material to wood for the production of roofing tiles.

The wood of Blighia sapida when its anatomical properties are known could serve as an alternative for the exorbitant economic timber species. However, there is little information provided on the anatomical properties of the lesser-used species which could trigger its optimum utilization and wide range acceptability by timber marketers and end-users. There is, therefore, the need to evaluate the anatomical properties of the wood species. Three Blighia sapida trees were selected and felled. Wood discs were obtained at the base, middle, and top of the trees, from which billets of 500 mm long were also obtained from pith to bark and then split into three zones; the innerwood, the middlewood, and the outerwood sections. By the specified standard for the anatomical property tests (Fibre length, Fibre diameter, Lumen width, and Cell wall thickness which were used for the estimation of derived morphological features; Slenderness coefficient, Flexibility ratio, Runkel ratio, Rigidity coefficient, Form factor, and Muhlsteph ratio as well as vessel length, vessel diameter, and vessel frequency) were all evaluated. B. sapida was found to have thick cell walls which might be a setback to the production of quality paper, but a comparison of the cell wall thickness with that of the pines validated B. sapida wood fibre suitability for the pulp and paper industries if other morphological indices meet up with the requirements for the production of paper. However, the fibre length was short and the mean Runkel ratio, one of the major determinants of a fibrous material's appropriateness for production of quality paper, recorded for B. sapida wood was higher than 1 which makes it not suitable for quality paper production but other fibrous utilisation purposes could be explored, such as the production of intermediate papers that require strength. The species vessel length observed was within the category of short length vessels and vessel diameter was within the category of medium vessels, which is an indication that the wood will be denser, thereby having considerable mechanical strength that compared well with other economic timbers species, which could be used for medium to heavy construction works and the use of fillers will not also be employed to produce smooth the surface of quality paper during production.

The architecture and structure of cereal spikes are key indicators of quality and yield and are determined by both genetic and environmental factors. Traditional phenotyping methods for cereal spike trait measurements rely largely on manual work and are often qualitative or destructive, which leads to loss of spatial information. In this study, by using the newly installed X-ray computed tomography (X-ray CT) system at the Plant Accelerator (Australian Plant Phenomics Facility), we developed a high-throughput and non-destructive method to analyse cereal spikes. The fully automated algorithm generates detailed grain traits measurement, including count, weight, size, surface area, sphericity and spatial position. The average scan time required per sample cassette is under 7 minutes for 30 cereal spikes. Various cultivars of wheat, barley, oat and sorghum have been tested, and the results have confirmed the high accuracy and efficiency of using the X-ray CT system in grain studies. To further utilise the obtained 3D information, a pipeline for analyse spike and spikelet morphological traits has been developed for wheat spikes and oat panicles. This method allows to study the spikelet morphological traits by categorising the spikelets base on grain count, volume and weight, which can potentially bring the insights of the relationship between the development of single or multiflorous spikelets and grain quality and yield. The innovative X-ray CT system can efficiently generate grain and spike traits in high-throughput and non-destructive way, which provides a new method to contribute to a better understanding of cereal screening and breeding directions.

Although the expression of several connexins has been reported in the central nervous system, only Cx36 and Cx45 have been undoubtedly demonstrated as part of electrical synapses. Dopamine neurons of the substantia nigra pars compacta (SNc), whose electrical activity is important for goal directed behavior, learning, working memory, reward and modulation of motor activity, communicate with other Dopamine neurons through electrical synapses. However, the expression profile of connexins in the SNc has only been determined in the rat. Considering that electrical synchronization of Dopamine neurons could have important roles in the modulation of levels of Dopamine released both locally and in the areas of innervation, and therefore in the functioning of Dopamine circuits, we decided to determine the expression profile of connexins in freshly isolated cells from SNc of adult mice. Using single cell RT-PCR, we show that a subset of DA neurons, and neurons of glutamate and GABA phenotypes, express Cx45 as well Cx26, Cx30, Cx31.1, Cx32 and Cx43, but not Cx36. Thus our results suggest that in adult mice, Cx45 is the connexin used by some of DA neurons of the SNc to be electrically coupled. Our results also suggest that glutamate and GABA neurons of the SNc, could also be electrically coupled with DA neurons. Despite the inability of the other connexins to form functional gap junctions in neurons, the expression of Cx26, Cx30, Cx32 and Cx43 may be the reflect of the ability of the neurons of SNc to release neuromodulators through hemichannel activity.

Major depressive disorder (MDD) is a serious mental disorder with unclear pathogenesis. ProBDNF is the precursor protein of brain derived neurotrophic factor (BDNF) expressed in the central nervous system and peripheral tissues. Previous studies showed that the blood levels of both proBDNF and inflammatory cytokines in MDD were increased, but which blood cell types express proBDNF and its receptors is not known. Furthermore, the relationship between proBDNF/p75NTR and inflammatory cytokines in peripheral blood of MDD is unclear. Peripheral blood mononuclear cells (PBMCs) and serum were obtained from depressive patients (n=32) and normal donors (n=20). Using flow cytometry analysis, we examined which blood cells express proBDNF and its receptors. Q-PCR and Western blots showed proBDNF, p75NTR and sortilin levels were significantly increased in PBMCs from MDD patients compared with that from the normal donors. Flow cytometry studies showed that proBDNF and p75NTR were present mainly in CD4+ and CD8+ T-cells and CD19+ B cells. The number of proBDNF and p75NTR positive CD4+, CD8+ T cells and CD19+ B cells from MDD patients was increased and subsequently reversed after therapeutic management. Inflammatory cytokines in PBMC from MDD patients were also increased. The levels of IL-1β and IL-10 were also positively correlated with the major depression scores, while the levels of TNF-α and IL-6 were negatively correlated with the major depression scores. Intriguingly, the levels of sortilin was positively correlated with IL-1β. Our data also suggest that proBDNF/p75NTR/sortilin signaling pathway in T and B cells may serve as biomarkers for MDD.

Generally, wind speed alters continuously during a day and lead to fluctuating output power of a wind farm. Connecting such a wind farm to the transmission line of grid causes a malfunction in the performance of the backup zone of the distance relays due to the random nature of generation and the number of connected wind turbines (wind farm penetration). In this study, a new adaptive setting groups-based method has been proposed to set the second zone of the distance relay in the grid with a wind farm equipped with a doubly fed induction generator (DFIG). In this method, we also taken into account the uncertainty of wind fluctuations and the availability of wind turbines. A Markov model is developed to implement these features. To determine the impedance setting of each of the set groups of the second zone in the distance relays of the remote bus, the obtained impedances are clustered in four clusters by using the combination of K-means and particle swarm optimization (PSO) algorithms. Finally, details of the analysis results of this issue have been compared with other methods available in the literature. The validity and accuracy of the proposed approach also have been assayed and confirmed.

This paper proposes an intelligent approach based on the empirical Fourier decomposition (EFD) to identify harmonic sources at the point of common coupling (PCC) when different inverter-based distributed generations (DGs) like microturbine (MT), Battery energy storage system (BESS), photovoltaic (PV), superconducting magnetic energy storage (SMES), wind turbine with a permanent magnet synchronous generator (PMSG), and doubly-fed induction generator (DFIG) wind turbine are presented. In order to decrease memory storage and computational burden, strife feature selection is used. Applying just voltage signals consumes less processing time and decreases measurement devices. Moreover, the whale optimization algorithm (WOA) as the optimizer of the parameters of the support vector machine (SVM) classifier is used. Consequently, the results from the proposed method can be helpful for both engineers and researchers to plan and develop a better strategy to mitigate harmonic distortion.

A document by Jadhav Chakradhar. Click on the document to view its contents.

Based on 2001-2021 panel data, this paper uses ESDA to reveal the spatial distribution characteristics of patent applicants in China, and applies panel regressions to estimate influencing factors. It reveals that the distribution of patent applicants in China is strongly uneven, with hotspots being Beijing-Tianjin-Hebei, Yangtze River Delta and Pearl River Delta, cold spots being central, western and northeastern regions. In spatial regression, three key variables all have significant positive influences on patent applicants, and moderating effect of ‘Industrial diversity’ is also significantly positive. The spatial regression coefficient lambda is significantly positive, indicating a spatial spillover effect.

Multiple approaches in recent years have been implemented to address the persistent shortage of heart donors, including a recent modification of UNOS heart allocation system, expanding donor acceptance criteria, and adoption of novel techniques to utilize hearts from donors with circulatory death. The opioid epidemic has resulted in an exponential increase in deaths in the United States in recent years, particularly affecting younger adults. A recent analysis of UNOS database by Jenser et al. reveals a relative underutilization of heart donors with cardiovascular mechanism of brain death which provide similar long-term survival as donors with other mechanisms of brain death, highlighting the potential role of these donors to provide life saving cardiac allografts and mitigate the persistent shortage of hearts for transplantation.

Machine learning methods can be used as robust techniques to provide invaluable information for analyzing biological samples in pharmaceutical industries, such as predicting the concentration of viral particles of interest in biological samples. Here, we utilized both convolutional neural networks and random forests to predict the concentration of the samples containing measles, mumps, rubella, and varicella-zoster viruses (ProQuad®) based on Raman and absorption spectroscopy. We prepared Raman and absorption spectra datasets with known concentration values, then used the Raman and absorption signals individually and together to train RFs and CNNs. We demonstrated that both RFs and CNNs can make predictions with R2 values as high as 95%. We proposed two different networks to jointly use the Raman and absorption spectra, where our results demonstrated that concatenating the Raman and absorption data increases the prediction accuracy compared to using either Raman or absorption spectrum alone. Additionally, we further verified the advantage of using joint Raman-absorption with principal component analysis (PCA). Furthermore, our method can be extended to characterize properties other than concentration, such as the type of viral particles.

Terrestrial arthropods are abundant and diverse with outsized ecological and economic importance. Our ability to monitor this diversity is hampered by the variety of sampling techniques and taxonomic expertise required to catalog the species in an area. DNA metabarcoding approaches show promise but have mainly been limited to trapping studies where DNA is extracted from captured individuals. Here we illustrate the promise of terrestrial plant surfaces as reservoirs of environmental DNA (eDNA) that is rich in arthropod biodiversity information. We posit that collection of surface eDNA will enable easier and more rapid arthropod inventories. We collected 40 paired samples using two novel terrestrial surface eDNA sampling techniques – ‘roller’ tree bark and ‘spray’ foliage sampling – in a New Jersey, USA pine barrens forest. Metabarcoding using two primer sets (COI and 16S) revealed the presence of 177 arthropod families (from 21 orders), representing 80% of the family-level diversity expected in the area based on accumulation curves. Spray samples revealed more families than roller (148 vs. 126), while the two methods showed distinct, though overlapping, community composition. The two primer sets revealed similar alpha diversity, although they also captured different taxonomic subsets. A more limited comparison of roller and spray sampling with traditional aquatic and soil eDNA samples revealed a greater family diversity in surface samples, especially compared with soil. Our study highlights the value of eDNA metabarcoding surveys for achieving the elusive goal of rapid, cost-effective arthropod inventories, and thus realizing a range of ecological research and management goals.

Should We Limit Antiarrhythmic Drug Choice in Patients

Background: Since 2013, the OECD has included patient experience indicators in OECD Health Statistics, and most of countries have submitted patient experience survey data. This movement of the international community became the basis for strengthening patient participation in the provision of medical services and ensuring the quality of medical care. Along with international discussions, the Ministry of Health and Welfare of Korea recognized the importance of confirming patient experiences and introduced a medical service experience survey for all citizens in 2017. Based on this background, this study examined the factors that influence the ‘Overall Satisfaction’ and ‘Intention to Recommend’ of medical institutions used using the Korea Medical Service Experience Survey (2019-2021). At this time, the Top-box rating model used in the United States was applied. Methods: This study used the data of Medical Service Experience Survey in Korea. The data collected for data analysis were from 2019 to 2021 (Medical service period: 2018.07.01. ~2021.06.30). In this study, only those who used inpatient services (15 years of age or older) were included because they spent a long time in a medical institution and had an intensive experience, and a total of 1,105 subjects were included in the analysis. Results: According to the analysis results, self-rated health and bed type had an effect on overall satisfaction with medical institutions. In addition, the type of economy activity, living area, self-rated health, the type of bed, and the type of nursing service affected the intention to recommend. And it was confirmed that overall satisfaction with medical institutions and intention to recommend them were higher in the 2021 survey than in 2019. Conclusion: These results suggest the importance of government policy on resources and systems. In particular, through the case of Korea, it was found that the policy of reducing beds in multi-person rooms and integrated nursing care services had an important effect on improving the patient’s experience in using medical institutions and quality of care.