During the COVID-19 pandemic, multiple skin manifestations have been described. These include an urticarial rash, morbilliform rash, maculopapular rash, vascular lesions, and varicella-like eruptions. A 30-year-old woman presented with a mild cough, then hives and pruritic rash for 3 days, followed by fever, dyspepsia, and throat pain for one day.

Sweet syndrome (SS) is an inflammatory disease with clinical and histological characteristics. SS is usually associated with important neutrophilic infiltrates on histological examination of skin biopsies. A few cases of SS with dense eosinophil infiltrate have been described. Herein, we report a new case of eosinophil-rich SS.

We experienced a case of iatrogenic intramucosal esophageal dissection in a patient who had difficulty inserting a gastric tube. CT is useful for diagnosis.

Acquired Hemophilia A in Internal Medicine: A Case ReportBorro M, Tassara R, Paris L, Artom N, Brignone M, Rebella L, Tassara RTo the Editor,Acquired hemophilia A (AHA) is a rare bleeding disorder in patient with a previously normal hemostasis characterized by the presence of neutralizing autoantibodies, named inhibitors, whose target is the coagulation factor VIII (FVIII) (1). Typically, AHA incidence is associated with pregnancy and older age, e.g over 60 years old (2). Over 50% of patients with AHA have comorbidities, frequently autoimmune disorders, or malignancy (2, 3). Clinical manifestations may range from asymptomatic to life-threatening bleeding but, subcutaneous hematomas are present in 80% of patients and frequently the first sign of the disease (4). Moreover, especially in elderly with multiple chronic diseases, patient ongoing medications, i.e. antiplatelet agents and anticoagulants, may interfere with the clinical picture and delay the correct diagnosis (1). Laboratory investigations lead the diagnostic pathway of AHA and are characterized by prolonged activated partial thromboplastin time (APTT), confirmed with the APTT mixing study, various levels of reduced FVIII activity (usually ranging from <1% to 40%) and the presence of autoantibodies detected by the Bethesda assay or by enzyme-linked immunosorbent assay (5). The concomitant presence of a prolonged prothrombin time should be attributed to other causes, e.g. anticoagulants (1). In elderly patients, morbidity and mortality associated with AHA are extremely high and, unfortunately, because of the rarity of the condition and frequent severe clinical picture at presentation, comparative studies are lacking (1). Recent international recommendations suggest that both recombinant activated factor VII (eptacog alfa) and activated prothrombin complex concentrate and recombinant porcine factor VIII (susoctocog alfa), named bypassing agents, can be administered as first-line hemostatic treatment options (1). Because of its lower efficacy and the risk of fluid overload, heart failure and severe hyponatremia, especially in elderly patients, the use of human factor VIII concentrates associated with desmopressin is limited to those cases where therapy with bypassing agents is not available (1, 6). Here, we report a clinical case of AHA in an elderly patient presenting with diffuse subcutaneous hematomas and anemia, successfully treated with susoctocog-alfa.Case presentationA 79-year-old women was admitted to the hospital for lipothymia and presence of non-traumatic subcutaneous hematomas in the four limbs. Medical history showed ischemic heart disease with a six-month-earlier Non-ST-segment elevation myocardial infarction treated with percutaneous angioplasty and stenting, monoclonal gammopathy, hypertension and dislipidemia. Ongoing therapy was Nebivolol 5 mg, acetyl salicylic acid 75 mg, Perindopril 10 mg, Rosuvastatin 20 mg, and Furosemide 25 mg bid. Ticagrelor 90 mg was stopped ten days earlier in agreement with the cardiologic follow-up. Physical examination showed hypotension, multiple subcutaneous hematomas at various stage spread both to thighs, legs and arms. Laboratory tests showed worsening moderate-to-severe normocytic normochromic anemia, stage-I acute kidney injury, and prolonged activated partial thromboplastin time (aPTT) with normal prothrombin time (PT), 1,68 ratio and 78% respectively. Serum protein electrophoresis showed the known presence of a minor band in the gamma region (estimated 6%). No Bence Jones proteinuria was found. Patient was treated with multiple red blood cell concentrates and normal saline rehydration. Mixing test showed a persistent prolonged aPTT, thus suggesting the presence of factor inhibitors. Further investigation showed a reduced FVIII activity (2%) with normal activity of FIX, FXI and FXII. According to the International recommendations published in 2020 by Tiede et al. (1), acquired hemophilia A was diagnosed and confirmed with the positive finding of autoantibodies against FVIII detected by the Nijmegen modified Bethesda assay (38,4 N.B.U.). As recommended, methylprednisolone 1 mg/Kg and oral cyclophosphamide 2 mg/kg/day were started as soon as possible. Accordingly, the presence of porcine FVIII inhibitor was excluded. In order to limit the thromboembolic risk, especially related to the recent cardiac procedure, the rpFVIII Susoctocog alpha Obizur® was used as first-line therapy (loading dose: 100 U/kg; subsequent six doses: 50 U/Kg). FVIII levels were measured immediately before and after the first loading dose and resulted 5% and 82%, respectively. In few days, no other subcutaneous hematomas nor internal bleeding were noticed, and supportive transfusions were not needed anymore. A further dosage of autoantibodies against FVIII showed a significant reduction (3,4 N.B.U.). When hemoglobin levels and aPTT were persistently stable (12,6 g/dL and 1,06 ratio, respectively), the patient was discharged with indication to continue oral prednisone and cyclophosphamide for four weeks. At first laboratory follow-up visit FVIII and aPTT were 64% and 1,01 ratio, respectively. At first follow-up visit coagulation tests were normal, as well as hemoglobin levels. Patients continued therapy with cyclophosphamide 100 mg and tapered steroid therapy. At the end of eighth therapy cycle, given the complete stability of coagulation tests and hemoglobin levels, cyclophosphamide was completely discharged. Further follow-up visit showed stability of all parameters.DiscussionIn AHA patients, the bleeding is the first sign and the trigger for diagnosis in 89% of cases (2). Because of the high risk of bleeding and the significant bleed-related morbidity, irrespectively of the bleeding phenotype of the patient, immunosuppressive therapy (IST) should be started as soon as possible, simultaneously to the hemostatic treatment (7). From the first guidelines, back in 2009 (6), to the most recent one in 2020 (1) IST has changed significantly: updated recommendations suggest the use of corticosteroids alone for 3-4 weeks in those patients with FVIII ≥1% and inhibitor ≤20 BU and the use of a 3-4 week combination therapy (corticosteroid and cytotoxic agent or rituximab) when FVIII <1% or inhibitor titer >20 BU (2). In contrast with congenital hemophilia, because of the high risk of bleeding and the lack of protection from new bleeding until FVIII is over 50%, the hemostatic treatment should be started simultaneously to IST. The choice of the most appropriate hemostatic treatment is usually based on availability of agents, the anti-porcine titer, costs, monitoring requirements, personal experience, and the risk of thrombotic events and safety profile (1, 8). Treatment with both recombinant activated factor VII, activated prothrombin complex concentrate and recombinant porcine factor VIII is associated with a certain risk of arterial and/or venous thrombotic events, especially in elderly patients with risk factors (e.g. cardiovascular disease), recent thromboembolic events and immobility due to the present bleeding (1). The administration of recombinant porcine factor VIII both at an initial dose of 200 U/kg with subsequent doses assigned by clinical response and FVIII activity (9) and at a reduced dosage (100 U/Kg of loading dose and subsequent doses at 50 U/Kg) has proven to maintain excellent hemostatic efficacy with a possibly lower risk of thromboembolic events in small case series (10-13) and in the pivotal phase II/III trial (10, 14) if compared with other bypassing agents. Specifically, recombinant factor VIIa (eptacog alfa activated) showed a thromboembolic risk of 0-5% and 2,9% in a systematic review (15) and in the EACH2 registry (16), respectively; the thromboembolic risk related to the administration of activated prothrombin complex concentrate was found 4,8% in the EACH2 registry (16). In our case report, loading dose and subsequent doses were administered at a lower dosage showing efficacy in hemostasis without thromboembolic events, despite patient age, comorbidity, and recent myocardial infarction treated with stenting. Moreover, as described in the international recommendations, the efficacy and safety of Susoctocog alfa can be monitored by measuring the FVIII activity using readily available standard FVIII assays, thus guiding the adequate dosing (1).In conclusion, although it is a rare condition, clinicians should be aware of AHA as a potential cause of bleeding in patient admitted to the hospital for hemorrhage and hematomas, especially in elderly patients with comorbidities and often ongoing with anti-platelets and/or anticoagulant treatment that may mime and mask the characteristics of the disease. Moreover, the choice of the most adequate hemostatic approach is challenging: clinicians should correctly balance the bleeding risk and the thromboembolic risk in the context of the clinical situation of the patient.Reference list1. Tiede A, Collins P, Knoebl P, Teitel J, Kessler C, Shima M, et al. International recommendations on the diagnosis and treatment of acquired hemophilia A. Haematologica. 2020;105(7):1791-801.2. Knoebl P, Marco P, Baudo F, Collins P, Huth-Kuhne A, Nemes L, et al. Demographic and clinical data in acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2). J Thromb Haemost. 2012;10(4):622-31.3. Napolitano M, Siragusa S, Mancuso S, Kessler CM. Acquired haemophilia in cancer: A systematic and critical literature review. Haemophilia. 2018;24(1):43-56.4. Kruse-Jarres R, Kempton CL, Baudo F, Collins PW, Knoebl P, Leissinger CA, et al. Acquired hemophilia A: Updated review of evidence and treatment guidance. Am J Hematol. 2017;92(7):695-705.5. Tiede A, Klamroth R, Scharf RE, Trappe RU, Holstein K, Huth-Kuhne A, et al. Prognostic factors for remission of and survival in acquired hemophilia A (AHA): results from the GTH-AH 01/2010 study. Blood. 2015;125(7):1091-7.6. Huth-Kuhne A, Baudo F, Collins P, Ingerslev J, Kessler CM, Levesque H, et al. International recommendations on the diagnosis and treatment of patients with acquired hemophilia A. Haematologica. 2009;94(4):566-75.7. Holstein K, Liu X, Smith A, Knobl P, Klamroth R, Geisen U, et al. Bleeding and response to hemostatic therapy in acquired hemophilia A: results from the GTH-AH 01/2010 study. Blood. 2020;136(3):279-87.8. Tiede A. Critical Bleeding in Acquired Hemophilia A: Bypassing Agents or Recombinant Porcine Factor VIII? Hamostaseologie. 2020.9. Kruse-Jarres R, St-Louis J, Greist A, Shapiro A, Smith H, Chowdary P, et al. Efficacy and safety of OBI-1, an antihaemophilic factor VIII (recombinant), porcine sequence, in subjects with acquired haemophilia A. Haemophilia. 2015;21(2):162-70.10. Tarantino MD, Cuker A, Hardesty B, Roberts JC, Sholzberg M. Recombinant porcine sequence factor VIII (rpFVIII) for acquired haemophilia A: practical clinical experience of its use in seven patients. Haemophilia. 2017;23(1):25-32.11. Martin K, Kasthuri R, Mooberry MJ, Chen SL, Key NS, Ma AD. Lower doses of recombinant porcine factor VIII maintain excellent haemostatic efficacy. Haemophilia. 2016;22(6):e549-e51.12. Stemberger M, Mohnle P, Tschop J, Ney L, Spannagl M, Reincke M. Successful bleeding control with recombinant porcine factor VIII in reduced loading doses in two patients with acquired haemophilia A and failure of bypassing agent therapy. Haemophilia. 2016;22(5):e472-4.13. Zanon E, Pasca S, Borchiellini A, Lodigiani C, Molinari AC, Ambaglio C, et al. Susoctocog-alfa (Obizur((R))) in the treatment of nine elderly patients with acquired haemophilia A: an Italian multicentre real world experience. Blood Transfus. 2020;18(4):312-21.14. Burness CB, Scott LJ. Susoctocog Alfa: A Review in Acquired Haemophilia A. Drugs. 2016;76(7):815-21.15. Tiede A, Worster A. Lessons from a systematic literature review of the effectiveness of recombinant factor VIIa in acquired haemophilia. Ann Hematol. 2018;97(10):1889-901.16. Baudo F, Collins P, Huth-Kuhne A, Levesque H, Marco P, Nemes L, et al. Management of bleeding in acquired hemophilia A: results from the European Acquired Haemophilia (EACH2) Registry. Blood. 2012;120(1):39-46.

Robinow syndrome is an autosomal dominant and recessive congenital skeletal dysplasia characterized by prominent craniofacial features, skeletal abnormalities and other anomalies. We describe the clinical findings of a female patient who applied for dental treatment and was diagnosed with Robinow syndrome associated with ROR2.

We report an atypical presentation of a current disease to highlight the importance of making a correct diagnosis of scabies surrepticius in front of any itchy dermatosis especially in elderly patients. The misdiagnosis of this disease results in extensive infestation, especially with the use of corticosteroids.

Ablation strategies remain poorly defined for persistent atrial fibrillation (AF) patients with recurrence despite intact pulmonary vein isolation (PVI). As the ability to perform durable PVI improves, the need for advanced mapping to identify extra-PV sources of AF becomes increasingly evident. Multiple mapping technologies attempt to localize these self-sustained triggers and/or drivers responsible for initiating and/or maintaining AF; however, current approaches suffer from technical limitations. Electrographic flow (EGF) mapping is a novel mapping method based on well-established principles of optical flow and fluid dynamics. It enables the full spatiotemporal reconstruction of organized wavefront propagation within the otherwise chaotic and disorganized electrical conduction of AF. Given the novelty of EGF mapping and relative unfamiliarity of most clinical electrophysiologists with the mathematical principles powering the EGF algorithm, this paper provides an in-depth explanation of the technical/mathematical foundations of EGF mapping and demonstrates clinical applications of EGF mapping data and analyses.

The future of CABG can be bright if cardiac surgeons will change the paradigm followed so far and will return in history, abandoning the current comfortable life and accepting the burden represented by the cost of innovation, which has a path already mapped out but not sufficiently trodden for guilty lack of commitment.

Title Page:Title: Letter To The Editor: Gastrointestinal complications after cardiac surgery: Incidence, predictors, and impact on outcomesArticle Type: Letter To The EditorCorrespondence: 1. Sapna goindaniContact no: +971 54 344 9435. Email: sapnagoindani123@gmail.comInstitute: Peoples University of Medical and Health Sciences For Women (PUMHSW)Address: Flat no 9, building no 10 bastakia building, Al hamriya bur dubai, dubaiORCID: 0000-0003-4906-8463Co-Authors: 2. Roomi rajaContact No: +92-3342946940. Email: Romirajagoindani@yahoo.comInstitute: Ziauddin University KarachiAddress: Hemilton Courts Block G-1 Flat 408 Near Teen Talwar Clifton KarachiORCID: 0000-0001-9104-3644Co-Authors: 3. Satesh KumarContact No: +92-3325252902. Email: Kewlanisatish@Gmail.ComInstitute: Shaheed Mohtarma Benazir Bhutto Medical College Liyari, KarachiAddress: Parsa Citi Garden East, KarachiORCID: 0000-0001-7975-6297Word Count: 340Conflict of interest : NoneAcknowledgment : NoneDeclaration: NoneDisclosure : NoneFunding : None

DISCUSSION – Left brachiocephalic vein is 6 cm long; it begins behind the sternal end of the clavicle, anterior to the cervical pleura by union of the left internal jugular vein and the left subclavian vein. It descends obliquely to the right, behind the upper half of the manubrium sterni, up to the sternal end of the first right costal cartilage, uniting here with right brachiocephalic vein to form SVC. The aortic arch is inferior to this vein. The left retro-aortic bracheocephalic vein is rare entity which was first described by Kerschner.[(1)](#ref-0001) Incidence of left retro-aortic bracheocephalic vein is noted between 0.2 to 1%.[(2)](#ref-0002) Aorto-pulmonary window is a rare cardiac condition, first described by Eliotson in 1830[(3)](#ref-0003) with an incidence of 0.2% - 0.3% of all congenital cardiac lesions.[(4,5)](#ref-0004) Three standard approaches for surgical closure of aorto-pulmonary window have been described in literature include: trans-aortic approach, trans-window approach, trans-pulmonary approach. Trans-window approach is also known as sandwich repair of aorto-pulmonary window.[(6)](#ref-0006) The left retro-aortic brachiocephalic vein with tetralogy of fallot and coarctation of aorta are noted. The left retro-aortic brachiocephalic vein with aorto-pulmonary window is very rare case and has not been reported previously. In our case the patient was admitted for AP window closure after complete pre-operative evaluation. Cardiac computed tomography reported 2.2cm aorto-pulmonary window with the left retro-aortic brachiocephalic vein. After obtaining parental consent for surgery, median sternotomy was performed. Thymus was excised and pericardium was opened longitudinally. By careful dissection, the left brachiocephalic vein was identified behind the distal ascending aorta adjacent to the AP window. Aorta was dissected off the brachiocephalic vein meticulously. Due to left retro-aortic brachiocephalic vein, aortic cannulation had to be done more caudally to avoid obstruction of vein. Aorta was cannulated and clamped without injury to the brachiocephalic vein. Attention was paid to avoid injury of the brachiocephalic vein during encircling the SVC for snaring. Aorto-pulmonary window was closed with PTFE patch through trans-window approach under mild hypothermia.[(6)](#ref-0006) Clinical implication of retro-aortic brachiocephalic vein is very important. More caudal cannulation of SVC is required in left brachiocephalic vein; but in AP window setting, this is more difficult as work space for closure of the defect is also required. Injury may occur to the vein during clamping of aorta. Left retro-aortic brachiocephalic vein may cause technical difficulty during central venous line placement through left arm approach. CONCLUSION- Being the rarest combination of left retro-aortic brachiocephalic vein and aorto-pulmonary window, certain things have to be taken care of like clamping of aorta, SVC cannulation, central vein catheter insertion, snaring of SVC. Pre-operative CT scan is also important to avoid intra-operative surprises.

Background: The incidence of brain tumours in India equate to half of those in the developed world. Delayed diagnosis is associated with a higher risk of life-threatening neurological complications at presentation and poor cognitive outcomes amongst survivors. Early detection and treatment is crucial for improving outcomes. Aims: The aim of this study was to analyse baseline diagnostic intervals for paediatric brain tumours in Tamil Nadu. Methods: Data for this retrospective study was collected via questionnaire across 8 different hospitals in Tamil Nadu. It consisted of 14 questions where doctors were asked to record data items including the date of symptom onset, first presentation to healthcare and date of diagnosis. Results: 114 children were diagnosed with a brain tumour between January 2018 – October 2020. The average diagnostic interval was 9.3 weeks (median 3.5 weeks), and the average patient interval is 6.1 weeks (median 0.6 weeks.). Low-grade tumours had the longest median total diagnostic interval of 6.6 weeks. The median total diagnostic interval was significantly higher in villages (7.9 weeks), as compared to patients located in District (4.8 weeks) and cities (2.3 weeks). Conclusion: Overall, the diagnostic interval for paediatric brain tumours were comparable to data in the UK. Moreover, all patients received an MRI within a day, indicating excellent infrastructure.. However, many low-grade and optic pathway tumours were unaccounted for. Tamil Nadu has one of the best healthcare systems in India and extending this methodology to areas with poorer healthcare provisions, is required to get representative national data.

Background: Chronic benign neutropenia (CBN) and autoimmune neutropenia (AIN) are notoriously difficult to differentiate in children owing to their indistinguishable clinical course and varying availability and accuracy in the methods of anti-neutrophil antibody detection. This study aims to investigate whether the presence of anti-neutrophil antibody has implications on the disease course in Chinese children with AIN, as well as evaluating the various methods including LABScreen MULTI, granulocyte agglutination test (GAT) and granulocyte immunofluorescence test (GIFT) in anti-neutrophil antibody detection. Procedure: Chinese children under 18 years of age with neutropenia ≤ 1.5 x 109/L lasting 6 months or more in our single center were recruited into the study between 2016 to 2018. Patients with secondary causes of neutropenia were excluded. Blood for anti-neutrophil antibody and genotyping was taken once at the time of recruitment and subsequently when neutropenia recovered to ≥ 1.5 x 109/L. A combination of two in-house methods including GIFT, GAT and commercial kit LABScreenTM multipanel were used for the detection of antibodies. The age of onset, age of recovery, duration of neutropenia, gender, serial neutrophil counts, incidence of invasive infection, use of G-CSF were examined. Results: Using combined testing methods, anti-neutrophil antibody was detected in 30.8 % of patients and positivity was associated with more severe neutropenia, higher likelihood of infection and slower and later recovery compared to those without antibodies. Conclusions: The presence of anti-neutrophil antibody was useful in predicting the clinical course of patients with AIN. The use of combined testing methods increased the detection rate.

Metabolic rate is a trait that may evolve in response to the direct and indirect effects of predator-induced mortality. Predators may indirectly alter selection by lowering prey densities and increasing resource availability or by intensifying resource limitation through changes in prey behaviour (e.g. use of less productive areas). In the current study we quantify evolution of metabolic rate in the zooplankton Daphnia pulicaria following an invasive event by the predator Bythotrephes longimanus in Lake Mendota, Wisconsin, US. This invasion has been shown to dramatically impact D. pulicaria, causing a ~60% decline in their biomass. Using a resurrection ecology approach, we compared the metabolic rate of D. pulicaria clones originating from prior to the Bythotrephes invasion with that of clones having evolved in the presence of Bythotrephes. We observed a 7.4% reduction in metabolic rate among post-invasive clones compared to pre-invasive clones, and discuss the potential roles of direct and indirect selection in driving this change.

Title: Reply to “Pro-arrhythmia with Anti-arrhythmic Drugs in Patients with Idiopathic Ventricular Arrhythmia: A Common Problem with Vague Definitions and Complex Interactions”Jacky K. K. Tang MD1 and Marc W. Deyell MD MSC1,2Heart Rhythm Services, Division of Cardiology, University of British ColumbiaCentre for Cardiovascular Innovation, University of British ColumbiaWord Count: 538 (including references)Address for correspondence:Dr. Marc William DeyellHeart Rhythm Services, St. Paul’s Hospital200 – 1033 Davie St.Vancouver, B.C., Canada, V6E 1M7Phone: 604-806-8256; Fax: 604-806-8723Email: mdeyell@mail.ubc.ca@MarcDeyellCompeting Interests: Dr. Deyell reports research grants from Biosense Webster and honoraria from Biosense Webster, Medtronic and Abbott.Funding: This work was supported by the UBC Division of Cardiology Academic Practice Plan.Drs. Hasdemir and Payzin have cogently brought up one of the primary challenges in studying patients with frequent premature ventricular complexes (PVCs) and evaluating the impact of therapy. They highlight, based on their prior study,(1) that a group of patients may actually experience a significant increase in PVC burden (>50%) with medical therapy, which obviously raises concerns that this may enhance deleterious effects of PVCs, particularly in the long term.With the advent of ambulatory monitoring, it was recognized early that PVC burden could be highly variable, leading to measurement error when using a 24-hour monitor. This error is highest when performing before-and-after studies of the effect of intervention on PVC burden, using single monitoring periods of 24 hours prior to and after intervention. In particular, spontaneous reductions in PVC burden can overestimate treatment effects. This error can be minimized in two ways, through serial monitoring (repeated measures) or longer-term monitoring (>48h). Indeed, an elegant study by Dr. Mullis and colleagues, using 14 day patch monitors, showed a median absolute day-to-day fluctuation in PVC burden of almost 10% among patients with a high burden of PVC.(2) Thus, an apparent “pro-arrhythmic” effect of a medication may simply reflect inefficacy and expected variation in PVC burden.In our prior work,(3) published in this journal and referenced by Drs. Hasdemir and Payzin, we were also limited by using only 24-hour ambulatory monitors to assess PVC burden. However, we did include a control group on no medical therapy, to mitigate the effect of measurement error, by obtaining an estimate of variation in PVC burden in the absence of therapy. In our study, we observed a “pro-arrhythmic effect” (>50% increase in PVC burden), in 2.5% (1/40) of patients on no medical therapy, 7.5% (4/53) on beta blockers/calcium channel blockers and 11.1%% (3/27) on class I/III antiarrhythmic therapy. Despite the trend, these were not significantly different (p=0.28 and p=0.14 for beta blocker/calcium channel blocker and class I/III antiarrhythmics versus no therapy).This does not negate a potential pro-arrhythmic effect of medical therapy in a minority of patients. However, more definitive proof of a pro-arrhythmic effect, distinguishing this from spontaneous variation in PVC burden, would require demonstration of a decrease in PVC burden with cessation of therapy. This would best be accomplished with a blinded, cross-over trial design.Drs. Hasdemir and Payzin remind us to always critically assess, and reassess, our therapies for patients with frequent PVCs. We must always evaluate whether treatment is warranted (in the majority of cases it is not), and whether patients are at risk for adverse events, particularly from class I and III antiarrhythmics. Frequent PVCs make physicians uncomfortable but we should not rush to treatment and expose patients to unnecessary harm.References:1. Turan OE, Aydin M, Odabasi AY, Inc M, Payzin S, Hasdemir C. Therapeutic Inefficacy and Proarrhythmic Nature of Metoprolol Succinate and Carvedilol Therapy in Patients With Idiopathic, Frequent, Monomorphic Premature Ventricular Contractions. Am J Ther 2021;29:e34-e42.2. Mullis AH, Ayoub K, Shah J et al. Fluctuations in premature ventricular contraction burden can affect medical assessment and management. Heart Rhythm 2019;16:1570-1574.3. Tang JKK, Andrade JG, Hawkins NM et al. Effectiveness of medical therapy for treatment of idiopathic frequent premature ventricular complexes. Journal of Cardiovascular Electrophysiology 2021;32:2246-2253.

Background and Purpose：As important components of lung tissue, endothelial cells (ECs) are associated with many lung diseases. The role of ECs dysfunction in idiopathic pulmonary fibrosis (IPF) and how to improve alveolar capillary barrier (ACB) to treat IPF is incompletely understood. Therefore we investigated the involvment of endothelial Sphingosine-1-phosphate receptor 1 (S1pr1) in PF and therapeutic effect of selective S1pr1 agonist IMMH002. Experimental approach：Databases of IPF patients and individuals without fibrosis were mined by Seurat. We generated an endothelial-conditional S1pr1 knockout (S1pr1+/−) mice and we also examined a bleomycin-induced model of pulmonary fibrosis (PF). We performed qRT-PCR,Western blot, Immunofluorescence staining and EC permeability experiments. Key results：Expression of S1pr1 in ECs was reduced markedly in IPF patients. Mice with endothelial-specific S1pr1 deficiency exhibited severer inflammation and fibrosis upon challenge with bleomycin. Significant accumulation of alpha-smooth muscle actin (α-SMA) was observed near vessels after S1pr1 deficiency, which indicated a potential connection between ACB injury and fibrosis. S1pr1 activation by a selective agonist IMMH002 could ameliorate PF by improving tight junctions in ECs and protects the ACB. Conclusion and Implications: Our results suggest that S1pr1 plays a significant role in ACB and it could be a potential target for IPF. Activation of S1pr1 with IMMH002 elicits a potent therapeutic effect in bleomycin-induced fibrosis by increasing tight junctions in endothelial cells and protecting the integrity of ACB therefore improve survial rate and lung function.

This Research Highlight showcases the Research Paper entitled, Big cohort metabolomic profiling of serum for oral squamous cell carcinoma screening and diagnosis, https://doi.org/10.1002/ntls.20210071

Seeing that coding React-JS can be repetitive and prone to errors like most other programming languages, which makes it a daunting task, Automatic Code Generation (ACG) tools exist to help tackle this. The current model used in most of the ACG tools for React-JS comes up with components which is a fraction of the entire application when it comes to coming up with the entire Create, Retrieve, Update and Delete (CRUD) applications. Developers still need to come up with the logic of how CRUD functionalities will be implemented in the code that was generated by these models. This study seeks to address this gap by proposing an enhanced automatic generating model for Single Page Applications (SPA) in React-JS coined CRUD-Bolt. The study employs the USE questionnaire to test its usability whereby 38 React-JS developers across the globe fill the questionnaire after testing it. The results are imported into Statistical Package for the Social Sciences (SPSS) to evaluate CRUD-Bolt. The outcome of the study is threefold: achieve an enhanced model coined CRUD-Bolt, make it available to developers, and test its usability via SPSS.

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This work proposed a transition sensitive finite state machine – TSFSM using the novel master-slave transition detector for low-power or high-speed applications. To solve the problems of hazard-free requirements and difficult synthesis of the exisiting locally clock finite state machine, TSFSM uses multi-bit XOR gate as the input burst detector and the local clock generator. The measured results show that the proposed implementation reduce the difficulty of its design and synthesis, and it also reduces the the area and power consumption by about 86% and 18.2%.

X-ray flaw detection is widely used in the non-destructive testing method for industrial pressure vessels and the intuitive defect information can be obtained through the X-ray film. Digitizing X-ray film and realizing online evaluation of weld information is a focus in this field. To meet the requirements of DS level in the EN1409 international standard, a 12-bit or 16-bit industrial camera must be used to digitize the X-ray film, to ensure that the obtained high-gray-scale image has more details and more obvious features. Due to the low resolution of the grayscale image by the human eye, there is a relatively large error when evaluating the weld seam information in the grayscale image with low overall brightness and contrast. In addition, when an ordinary 8-bit monitor displays the above grayscale image with a high bit depth, problems, such as loss of detail information and blurring of the image, will occur due to the mismatch of the bit depth, resulting in greater errors. Aiming at the above problems, this paper proposed an image enhancement algorithm for displaying high-bit RAW images on the low-bit monitor. The pseudo-color enhancement algorithm was used in high gray-scale weld images, and a reasonable chromatographic mapping relationship was formulated according to the visual characteristics of the human eye to solve the problem of information loss caused by bit depth mismatch. Through pseudo-color processing, the defect information and the background color of the weld showed different colors, which was convenient for the capture of defect information in the weld. Compared with the existing algorithms, various indicators have been greatly improved, enriching the amount of information and strengthening the image recognition effects.

Without the use of medicine drones, users are responsible for transporting goods at a high cost. The goal of this patient monitoring system is to identify people's health and, if necessary, administer medicine. The transportation drone is capable of finding healthcare information in a 360-degree rotation within the transportation infrastructure. Drone doctors are critical for the transportation of small gadgets such as drug treatments, blood leakages, and vaccines in the critical conditions of a heart patient, in event of failure of traffic location infrastructure, highway roads, or hospitals due to intense climate or site visitor congestion, and for the transportation of small gadgets such as drug treatments, blood leakages, and vaccines. When transmission is difficult, the self-maintaining drone is the format for quickly transporting drug treatments to the appropriate locations. The shipping drone equipped with an Ardupilot can drive in autopilot mode, which guides the drone to its destination. It has a 7-minute flying period and can deliver up to 2 kg of medicine. When the detected heartbeat is 94bpm and the fever range is 101 degree, a method has been presented in which an IoT Drone Doctor System distributes the first AID box to vulnerable patients and heart patients.

To date, there is no effective vaccine or antiviral therapy available to prevent or treat African swine fever virus (ASFV) infections. ASFV gene deletion strains have been proposed as promising anti-ASFV vaccine candidates. In recent years, most ASFV gene deletion strains worldwide have been recombinant strains expressing EGFP or mCherry as markers. However, a method for their wide range detection is still lacking. Therefore, in this study, a new triplex real-time PCR (RT-PCR) method was established for the broad and accurate differentiation of ASFV wild-type vs. gene deletion strains. We designed three pairs of primers and probes to target B646L, EGFP, and mCherry, and RT-PCR was used to detect these three genes simultaneously. The detection method prevented non-specific amplification of porcine reproductive and respiratory syndrome virus, porcine epidemic diarrhea virus, circovirus type 2, pseudorabies virus, and classical swine fever virus genes. The minimum copy number of standard plasmid DNA detected using triplex RT-PCR was 9.49, 30.20, and 9.60 copies for B646L, EGFP, and mCherry, respectively. Importantly, of the 1646 samples analyzed in this study, 67 were positive for ASFV, all corresponding to the wild-type virus. Overall, our data show that the triplex RT-PCR method established in this study can specifically identify both ASFV wild-type and gene deletion strains.

Plant-mediated effects on the susceptibility of insect herbivores to entomoviruses are well recognized, but the mechanisms by which plant secondary metabolites impact susceptibility are poorly understood. With widely targeted metabolomics analyses of three plants (Glycine max, Brassica oleracea, Ipomoea aquatica) that caused significant differences in caterpillar (Spodoptera exigua) viral susceptibility, we found four plant phenolics (genistein, kaempferol, quercitrin, coumarin) that increased susceptibility. Subsequently, we analyzed transcriptomes of caterpillars treated with nucleopolyhedrovirus (NPV) alone or with one the four plant phenolics to examine differences in metabolic pathways. We found that phenolic treatments caused significant differences in genes up-or-down regulating cytochrome P450, glutathione S-transferase and consistently caused significant down-regulation of the CXE18 gene regulating antennal esterase in caterpillars. This study found four phytochemicals can be potential candidate NPV synergist and sheds light on the mechanisms driving insect susceptibility to entomoviruses.

Marine microbial flagellates form an important part of marine ecosystems, and play an essential role in maintaining ecosystem functions. However, the underlying biogeographic processes and ecological effects that shape marine microbial flagellate communities (MFCs) on the geographical scale (~ 2,000 km) remain unclear, especially how their composition is related to movements of water masses. In this study, high-throughput sequencing of 18S rRNA genes was conducted to survey two size-fractioned groups (0.8–2.0 μm for pico-sized and 2.0–20 μm for nano-sized groups) of MFCs in three subtropic-tropic marginal seas of China. Furthermore, the impacts of environmental factors, spatial factors, and water masses on MFCs were explored and compared across different spatiotemporal conditions. The results demonstrate non-random biogeographic distributions of MFCs in the studied area. These distributions were affected by several ecological processes, such as environmental selection, dispersal limitation, neutral process, and interactions within communities. These processes were driven by complex water masses that formed on a geographical scale. Notably, environmental heterogeneity was identified as the principal determinant of MFCs in each sea area. However, the importance of spatial factors increased with the spatial scale, which weakened biotic interactions within the community on a geographical scale. This effect was more apparent in nano-sized MFCs, indicating stronger dispersal limitation because of their larger cells and weaker dispersal ability. In summary, this study expands the available knowledge on the dynamic biogeographic patterns of MFCs associated with water masses on a geographical scale where strong spatial and environmental gradients exist.