COVID-19 infection is still a mystery in terms of its long-term effect on health and its consequences on hematological disorders. In this article, we are presenting two cases of pediatric B-lymphoblastic leukemia (B-ALL) with a previous history of COVID-19 infection. Notably, in both the cases the fluorescence-in situ hybridization (FISH) studies showed pathologic alteration of the RUNX1 gene. The finding of this genetic alteration along with known pre-leukemic translocation ETV6-RUNX1, opens a door for further exploration of the “second-hit” hypothesis regarding an infectious agent precipitating development of B-ALL in a genetically susceptible individual.

The rare inverse latitudinal diversity gradient is almost neglected compared with the dominant latitudinal diversity gradient, and the underlying mechanism of this biodiversity pattern remains elusive, especially for invertebrates. Necrophage trogid beetles are a vertebrate-dependent family group that may potentially serve as an environmental indicator, but comprehensive distributional knowledge is lacking. Here, a geographical distribution dataset of 11321 coordinates belonging to 284 species (over 80% of Trogidae) was compiled, and pairwise dependencies of trogids and vertebrates were integrated. The diversity patterns of Trogidae were revealed by calculating species richness and performing endemicity analysis. To further illustrate the underlying richness-variable relationships, the relative effects of environmental factors on the richness of trogids were investigated by random forest analysis. The hotspots of trogid species richness and areas of endemism were both located in temperate zones, together generating a rare inverse latitudinal diversity gradient in which similar height bimodal peaks appeared in the mid-latitude temperate zone (near 30°S and 40°N). Climatic conditions and food availability combined to explain 21.94% of the variance in global trogid richness. This work first reported the global diversity pattern of necrophagous beetles at the specimen grade and supported the ‘resource-dependent hypothesis’. And the case study in trogids provides valuable insights into inverse latitudinal diversity gradient patterns. The loose linkage of trogids and vertebrates is another interesting insight, with implications for carefully using trogids as an indicator of vertebrate distribution.

Forecasting the impacts of changing climate on the phenology of plant populations is essential for anticipating and managing potential ecological disruptions to biotic communities. Herbarium specimens enable assessments of plant phenology across broad spatiotemporal scales. However, specimens are collected opportunistically, and it is unclear whether their collection dates—used as proxies of phenology—are closest to the onset, peak, or termination of a phenophase, or whether sampled individuals represent early, average, or late occurrences in their populations. Despite this, no studies have assessed whether these uncertainties limit the utility of herbarium specimens for estimating the onset and termination of a phenophase. Using simulated data mimicking such uncertainties, we evaluated the accuracy with which the onset and termination of population-level phenological displays (in this case, of flowering) can be predicted from natural-history collections data (in the absence of other biases not evaluated here), and how attributes of the flowering period of a species and temporal collection biases influence model accuracy. Estimates of population-level onset and termination were highly accurate for a wide range of simulated species’ attributes, but accuracy declined among species with longer individual-level flowering duration and when there were temporal biases in sample collection, as is common among the earliest and latest-flowering species. The amount of data required to model population-level phenological displays is not impractical to obtain; model accuracy declined by less than 1 day as sample sizes rose from 300 to 1000 specimens. Our analyses of simulated data indicate that, absent pervasive biases in collection and if the climate conditions that affect phenological timing are correctly identified, then specimen data can predict the onset, termination, and duration of a population’s flowering period with similar accuracy to estimates of median flowering time that are commonplace in the literature.

Soil and water conservation practices, governance processes, and governance effects can be regarded as elements that constitute a unique coupling system. In order to understand the operation of this coupling system, a structural equation model was used to determine the coupling paths and intensities based on field research data collected from 193 local households in Changting County, China during 2021. The results showed that the elements within the coupling system remained unchanged and the coupling state was steady, with the same coupling path directions in 2010 and 2020. However, the intensities of the coupling paths varied with different path coefficients, where they followed the order of: governance process (0.99) > governance effect (0.57) > coupling state (–0.39) in 2010; and governance process (0.94) > coupling state (0.92) > governance effect (0.17) in 2020. We conclude that although the elements were optimized to a certain extent during the evolution of the coupling system, the lack of harmony among ecological resources and industries detrimentally affected the dynamics of the coupling system. Thus, the government should focus on the harmonious development of ecological resources and the integration of industries to facilitate the high-quality development of ecological civilization.

Introduction Skin cancer affecting the nail unit is rare but is associated with morbidity, and melanoma has a high mortality rate. The principal treatment is surgical excision and methods can be classified into digit-sparing surgery or amputation. Digit-sparing surgery (wide excision or Mohs surgery) may be safe and effective for malignancies involving the nail unit in comparison to amputation if there is not bony invasion. The objective was to assess the efficacy and safety of different methods of surgical excision for skin cancer involving the nail unit. Methods Prospective comparative studies (randomised controlled, non-randomised controlled and prospective observational studies) of surgical excision for skin cancer of the nail unit in all participants were eligible for inclusion. We searched electronic databases, trials registers and conference abstracts. We checked the reference lists of included studies and related systematic reviews for further references to relevant studies, and we contacted experts to enquire if they were aware of any additional relevant trials. We used standard methodological procedures expected by Cochrane. The primary outcomes were overall survival, disease free survival and adverse events/outcomes at 30 days. The secondary outcomes were quality of life outcomes. We planned to use GRADE to assess the quality of the evidence for each outcome. Results We did not identify any studies that met the inclusion criteria for this review. We have been unable to assess our outcomes of overall survival, disease free survival, adverse events/effects and quality of life. Conclusions As we have not identified any studies for inclusion, we are unable to assess the efficacy and safety of different methods of surgical excision for skin cancer involving the nail unit. Prospective research, ideally in the form of a randomised trial, is required in this field. Registration Cochrane Database of Systematic Reviews 2021, Issue 5. Art. No.: CD014590.

The colonization of marine microorganisms, animals and plants on underwater surface forms marine biofouling. It has profound ef-fects on marine industries. To solve the problem, we proposed a strategy of Dynamic Surface Antifouling (DSAF), i.e., continuously changing surfaces can effectively inhibit biofouling organisms landing and adhering, and developed degradable polymer based ma-rine antifouling material. The degradation of polymer chain enables the surface dynamic or self-renewing even on static conditions. The final degradation products of these polymers are low molecular weight molecules, and do not produce marine microplastics. Meanwhile, the degradable polymers act as carriers and controlled release systems for antifoulants, further improving the antifoul-ing efficiency. This article reviews the development of dynamic surface antifouling materials.

A document by Tristan Dale. Click on the document to view its contents.

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Current methodologies of genome-wide Single Nucleotide Polymorphism (SNP) genotyping produce large amounts of missing data that may affect statistical inference and bias the outcome of experiments. Genotype imputation is routinely used in well-studied species to buffer the impact in downstream analysis and several algorithms are available to fill in missing genotypes. The lack of reference haplotype panels precludes the use of these methods in genomic studies on non-model organisms. As an alternative, machine learning algorithms are employed to explore the genotype data and to estimate the missing genotypes. Here, we propose an imputation method based on Self-Organizing Maps (SOM), a widely used neural networks formed by spatially distributed neurons that cluster similar inputs into close neurons. We follow a classical approach that explores genotype datasets to select SNP loci for each query missing SNP genotype to build training sets, and that initializes and trains the neural networks to finally use the SOM-derived clustering to impute the best genotype. To automate the imputation process, we have implemented GTIMPUTATION, an open source application programmed in Python3 and with a user-friendly GUI to facilitate the whole process. The method performance was validated by comparing its accuracy, precision and sensitivity on several benchmark genotype datasets with other available imputation algorithms. Our approach produced highly accurate and precise genotype imputations and outperformed other algorithms, especially for datasets from mixed populations with unrelated individuals.

Using high-throughput sequencing for precise genotyping of multi-locus gene families, such as the Major Histocompatibility Complex (MHC), remains challenging, due to the complexity of the data and difficulties in distinguishing genuine from erroneous variants. Several dedicated genotyping pipelines for data from high-throughput sequencing, such as next-generation sequencing (NGS), have been developed to tackle the ensuing risk of artificially inflated diversity. Here, we thoroughly assess three such multi-locus genotyping pipelines for NGS data, using MHC class IIβ datasets of three-spined stickleback gDNA, cDNA, and “artificial” plasmid samples with known allelic diversity. We show that genotyping of gDNA and plasmid samples at optimal pipeline parameters was highly accurate and reproducible across methods. However, for cDNA data, the same configuration yielded decreased overall genotyping precision and consistency between pipelines. Further adjustments of key clustering parameters were required tο account for higher error rates and larger variation in sequencing depth per allele, highlighting the importance of template-specific pipeline optimization for reliable genotyping of multi-locus gene families. Through accurate paired gDNA-cDNA genotyping and MHC-II haplotype inference, we show that MHC-II allele-specific expression levels correlate negatively with allele number across haplotypes. Lastly, sibship-assisted cDNA genotyping of MHC-I revealed novel variants and haplotype-based allelic segregation with a higher-than-previously-reported individual allelic diversity for MHC-I in sticklebacks. In conclusion, we here provide novel genotyping protocols for MHC-I and -II genes of the three-spined stickleback, but also evaluate the performance of popular NGS-genotyping pipelines and highlight the need for template-specific optimization for reliable multi-locus genotyping.

Pediatric erythroblastic transformation of JAK 2-mutated prefibrotic primary myelofibrosis with concurrent PHF6 mutationsTokiko Oshiro1, Satoru Hamada1, Sinobu Kiyuna1, Hideki Sakiyama1, Nobuyuki Hyakuna2, Tomoko Tamaki3, Hideki Muramatsu4, Koichi Nakanishi5Department of Pediatrics, University of Ryukyus HospitalOkinawa prefectural Red Cross Blood CenterDepartment of Pathology and Oncology, Graduate school of Medicine, University of RyukyusDepartment of Pediatrics, Graduate School of Medicine, University of NagoyaDepartment of Pediatrics, Graduate School of Medicine, University of The RyukyusCorrespondence: Satoru Hamada,Department of Pediatrics, Faculty of Medicine, University of Ryukyus, 207 Uehara, Nishihara-cho, Okinawa 903-0125, Japanshamada@med.u-ryukyu.ac.jpTo the Editor: Primary myelofibrosis (PMF) is a rare condition in children. According to the 2016 World Health Organization (WHO), classification of myeloproliferative neoplasms (MPN), PMF is divided into prefibrotic PMF (pre-PMF) and overt fibrotic PMF1. Pre-PMF is the proliferation of predominantly abnormal megakaryocytes and minimal or no reticulin fibrosis. Therefore, the lack of fibrosis in the early phase of thrombocytosis can be misdiagnosed as essential thrombocythemia2. One significant complication of MPN is leukemic transformation (LT); however, only a few cases of PMF in children have been reported3. The clinical utility of the three driver mutations in JAK2 , CALR, and MPL has been shown, especially when JAK2 is central to the pathogenesis of the MPN phenotype4. Additional mutations in ASXL1, SRSF2, IDH1/2, or EZH2 have been shown5. PHF6is an X-linked tumor suppressor gene with a somatic mutation that causes an aggressive type of myeloid neoplasm6. Here, we report a case of pediatricJAK2 -mutated pre-PMF with concurrent PHF6 mutations that transformed into AML within a year of diagnosis.A 14-year-old boy with no medical history was admitted to our hospital with lumbago. Physical examination revealed splenomegaly (5 cm below the costal margins). A complete blood count showed a white blood cell (WBC) count of 5.8×109/L, neutrophil count of 31%, lymphocyte count of 36%, red blood cell count of 7.34×109/L, hemoglobin concentration of 140 g/L, and platelet count of 1010×109/L. The patient was diagnosed with essential thrombocythemia based on bone marrow findings, which showed hypercellularity (80-100%), increasing with separated circled-multinucleated megakaryocytes, hyper-segmented-megakaryocytes, atypical megakaryocytes, and micromegakaryocytes (Figure 1A), and was treated with anagrelide. At this time, there were no blasts or reticulin fibers. The patient had no karyotypic abnormalities. After written informed consent was obtained, target capture-based next generation sequencing (NGS) was performed on bone marrow DNA for the following genes: MPL, ASXL1, CBL, JAK3, EZH2, IDH1, IDH2, JAK1, PHF6, SF 3B1, TET2, TP53, U2AF1, JAK2, NRAS/KRAS and IKZF1 by previous described methods7. Among these mutations, JAK2 V617F with mutant allele percentage 4% and PHF6 p.Q121Xmutation with 64% were identified. In addition, we generated an MPN gene panel (JAK2 V617F, JAK2 exon12, MPL W515L, MPL W515K, CALR type1-5 ) using DNA microarray methods (SRL International Inc. Japan) and only the JAK2V617F mutation was identified. As the platelet count decreased, his symptoms became well-controlled. However, teardrop-shaped red blood cells and myeloblasts were observed in the peripheral blood six months later, and we performed a bone marrow biopsy. Results indicated hypercellularity (80-100%) with moderate fibrosis (MF grade 1; Figure 1B). Therefore, ruxolitinib was administered for myelofibrosis. Five months later, he showed elevated lactate dehydrogenase (LDH) levels and thrombocytopenia. Bone marrow aspiration revealed increased cellularity with predominant erythropoiesis and 40% erythroblasts (Figure 1C). Flow cytometric analyses revealed 14% glycophorin A and 90% CD34 positive blast cells. No reticulin fibrosis progression was observed. The cytogenetic analysis revealed a normal karyotype. The patient was diagnosed with acute erythroleukemia secondary to PMF. He underwent HLA haploidentical peripheral blood stem cell transplantation(haplo-HCT) from his mother, using post-transplantation cyclophosphamide (PT-Cy) for graft-versus-host disease (GVHD) prophylaxis. The conditioning regimen consisted of total body irradiation (12 Gy delivered in six fractions from days -8 to -6), fludarabine (30mg/m2 from days -5 to -2), and cytarabine (3,000 mg/m2×2 from days -5 to -4). GVHD prophylaxis consisted of high-dose PT-Cy (50 mg/kg intravenously on days 3 and 4) in combination with tacrolimus and mycophenolate mofetil from day 5 onward. Infused donor cells were 5.4×106/kg CD34 cells and 4.0×108/kg CD3 positive T cells. Engraftment occurred on day 21, and complete chimerism was achieved on day 33. He had several transplantation-related complications, including grade II acute GVHD (gut), which was treated with prednisolone; BK virus-associated hemorrhagic cystitis; and bronchiolitis obliterans syndrome (Supplementary Figure). He has been in complete remission for 7 years after transplantation. Considering that the bone marrow features are characterized by increasing cellularity with atypical megakaryocytes at clinical onset, the patient should first be diagnosed with pre-PMF.Our patient developed AML (FAB M6) 11 months after the diagnosis of pre-PMF. In terms of time to progression, median time (range) to progression was 11.8 years (7.9-15.7 years) in pre-PMF8. According to the Dynamic International Prognostic Scoring System (DIPSS) Plus score, our case was classified as low-risk. Candidate genes contributing to LT from MPN to AML have been identified, including TP53, TET2, ASXL1, EZH2, IDH1/2, RUNX1, U2AF1, NRAS/KRAS , and SRSF2 5. The adverse impact of molecular characteristics on survival in pre-PMF and overt PMF has been reported as a high mutation risk in EZH2, ASXL1, IDH1, IDH2 , and SRSF2 8. In our case, no additional somatic alterations were detected; however, a PHF6 mutation was identified. Somatic PHF6 mutations have been found in 2–3% of AML6, 9. The percentage of blasts in the bone marrow tends to be higher in patients with myeloid malignancies harboringPHF6 mutations6. AML with high PHF6expression levels than controls correlated with shorter overall survival10. Furthermore, increased PHF6 levels may be associated with CD34 positivity10. In a case series of MPN with increased fibrosis and blast crisis, 22 patients withPHF6 mutations in MPN were enriched11. Thus,PHF 6 mutations can contribute to myeloid leukemic transformation in JAK2 -mutated pre-PMF.AcknowledgementsWe are grateful to our patients and his family. And we would like to thank our colleagues for helpful discussion regarding this case.Conflict-of-interestThe authors declare that there is no conflict of interest.【References】(1) Tefferi A. Primary myelofibrosis: 2017 update on diagnosis, risk-stratification, and management. Am J Hematol. 2016;91(12):1262-1271.(2) Edahiro Y, Araki M, Inano T, Ito M, Morishita S, Misawa K, Fukuda Y, Imai M, Ohsaka A, Komatsu N. Clinical and molecular features of patients with prefibrotic primary myelofibrosis previously diagnosed as having essential thrombocythemia in Japan. Eur J Haematol. 2019;102(6):516-520.(3) DeLario MR, Sheehan AM, Ataya R, Bertuch AA, Vega C, Webb CR, Lopez-Terrada D, Venkateswaran L. Clinical, histopathologic, and genetic features of pediatric primary myelofibrosis–an entity different from adults. Am J Hematol. 2012;87(5):461-464.(4) Nangalia J, Green TR. The evolving genomic landscape of myeloproliferative neoplasms. Hematology Am Soc Hematol Educ Program. 2014;2014(1):287-296.(5) Andrew J. Dunbar, Raajit K. Rampal, Ross Levine; Leukemia secondary to myeloproliferative neoplasms. Blood 2020;136(1):61–70.(6) Mori T, Nagata Y, Makishima H, Sanada M, Shiozawa Y, Kon A, Yoshizato T, Sato-Otsubo A, Kataoka K, Shiraishi Y, Chiba K, Tanaka H, Ishiyama K, Miyawaki S, Mori H, Nakamaki T, Kihara R, Kiyoi H, Koeffler HP, Shih LY, Miyano S, Naoe T, Haferlach C, Kern W, Haferlach T, Ogawa S, Yoshida K. Somatic PHF6 mutations in 1760 cases with various myeloid neoplasms. Leukemia. 2016;30(11):2270-2273.(7) Muramatsu H, Okuno Y, Yoshida K, Shiraishi Y, Doisaki S, Narita A, Sakaguchi H, Kawashima N, Wang X, Xu Y, Chiba K, Tanaka H, Hama A, Sanada M, Takahashi Y, Kanno H, Yamaguchi H, Ohga S, Manabe A, Harigae H, Kunishima S, Ishii E, Kobayashi M, Koike K, Watanabe K, Ito E, Takata M, Yabe M, Ogawa S, Miyano S, Kojima S. Clinical utility of next-generation sequencing for inherited bone marrow failure syndromes. Genet Med. 2017;19(7):796-802.(8) Guglielmelli P, Pacilli A, Rotunno G, Rumi E, Rosti V, Delaini F, Maffioli M, Fanelli T, Pancrazzi A, Pietra D, Salmoiraghi S, Mannarelli C, Franci A, Paoli C, Rambaldi A, Passamonti F, Barosi G, Barbui T, Cazzola M, Vannucchi AM; AGIMM Group. Presentation and outcome of patients with 2016 WHO diagnosis of prefibrotic and overt primary myelofibrosis. Blood. 2017;129(24):3227-3236.(9) de Rooij JD, van den Heuvel-Eibrink MM, van de Rijdt NK, Verboon LJ, de Haas V, Trka J, Baruchel A, Reinhardt D, Pieters R, Fornerod M, Zwaan CM. PHF6 mutations in paediatric acute myeloid leukaemia. Br J Haematol. 2016;175(5):967-971.(10) Mousa NO, Gado M, Assem MM, Dawood KM, Osman A. Expression profiling of some Acute Myeloid Leukemia - associated markers to assess their diagnostic/prognostic potential. Genet Mol Biol. 2021;44(1):e20190268.(11) Kurzer JH, Weinberg OK. PHF6 Mutations in Hematologic Malignancies. Front Oncol. 2021;11:704471.Figure legendsFigure 1A. Bone marrow aspiration at first visit(day-370).Square (A) shows a separated circular multinucleated megakaryocyte, (B) a hypersegmented megakaryocyte, (C) an atypical megakaryocyte, and (D) a micromegakaryocyte.Figure 1B. Bone marrow biopsy on day-170.Silver impregnation shows moderate myelofibrosis. Arrows indicate reticulin fibers.Figure 1C. Bone marrow smear (1000×, May-Grunwald-Giemsa stain). The smear shows abnormal megakaryoblasts with round or oval nuclei, loose chromatin, agranular cytoplasm with blebs.Supplemental Figure 1. Clinical course of patients.A bone marrow biopsy on day-170 shows myelofibrosis, and bone marrow aspiration on day-30 shows erythroleukemia. aGVHD, acute graft-versus host disease; PSL, prednisolone; TBI, total body irradiation; FLU, fludarabine; Ara-C, cytarabine; CY, cyclophosphamide; MMF, mycophenolate mofetil; Haplo-SCT, haploidentical stem cell transplantation; BMA, bone marrow aspiration; BMB, bone marrow biopsy; BM, bone marrow.

Significant racial/ethnic inequities in the uptake of differentiated influenza vaccines (DIVs) have been previously reported, though less is known about regional disparities. We conducted a retrospective longitudinal study (2014/15-2017/18 influenza seasons) among privately insured adults aged 65+ years in the US. The exposure was beneficiary’s area of residence (US Census Bureau division) and outcome was type of influenza vaccine: differentiated (High-Dose [HDV], adjuvanted, recombinant, and cell-based) versus standard-dose egg-based. Among those vaccinated in physician offices, beneficiaries in the East North Central region were twice as likely to receive a DIV vs those in the South Atlantic, whereas those in the East and West South Central were least likely. Disparities became more pronounced in models adjusted for individual and community characteristics, suggesting that crude uptake estimates understate the true magnitude of disparities. Regional disparities remained even in fully adjusted models, pointing to currently poorly understood factors that may include quality of healthcare, client health literacy and engagement, and other political and cultural factors.

Whether individuals choose to migrate or not is rapidly shifting in many populations. Exactly how and why environmental change alters migration propensity is not well understood. We built density-dependent structured population models to explore the coexistence of migrants and non-migrants, when they coexist, and when they do not. We find that carrying capacity in a seasonal environment determines the dominant type in the population. Partial migration can be maintained, or not, depending on where in the life cycle density-dependent operates. Bet-hedging also promotes partial migration. Our study disentangles density-dependence and density-independence in seasonal environments, providing insights into the coexistence of polymorphism, potentially explaining the rapid change in migration strategy observed.

Fatal visceral varicella in a child with newly diagnosed acute lymphoblastic leukemiaJulia Tabatabaia,b, Neysan Rafatc, Hendrik Wittd, Andreas Sauerbreie, Roland Zelle,Paul SchnitzlerbaCenter for Childhood and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany;bCenter for Infectious Diseases, Virology, University Hospital Heidelberg, Heidelberg, Germany; cDepartment of Neonatology and Pediatric Critical Care, University Children’s Hospital, University of Heidelberg, Mannheim, Germany;dPraxis für Kinder- und Jugendmedizin, Weinheim, Germany; eSection of Experimental Virology, Institute for Medical Microbiology, Jena University Hospital, Friedrich Schiller University of Jena, Jena, Germany

This paper presents a Lyapunov-based model reference controller for Buck converter operating under harmful disturbances. This strategy is an advanced version of the tuning method utilising Lyapunov stability function to reach a higher stability and a better disturbance rejection behavior in the practical applications. In addition, to reduce the computational burden and increase ease of implantation, Black-box technique is considered assuming no accurate mathematical model for the system. Lyapunov stability theory is used to enhance and tune the PID gain of this method with an adaptive mechanism while taking into account the real-time condition of a converter with regular changes. For this gain-based controller, an adaptive mechanism based on the Lyapunov concept is proposed, which can improve the stability and resilience of the system under various disturbances, particularly noise. Moreover, a Fuzzy-based PID controller and a PID technique with Particle swarm Optimization (PSO) algorithm are designed and compared with the presented Lyapunov-based technique. MATLAB\Simulink is utilized to examine the results of this improved controller. Additionally, this method produces better results in real-time contexts with faster dynamics and better frequency adaptation.

This work provides an asymptotically stable and robust tracking control scheme using a finite-time stable disturbance observer in the feedback loop, for an unmanned vehicle modeled as a rigid body. The dynamics of the system is discretized using a Lie group variational integrator in the form of a “gray box” dynamics model that also accounts for unknown additive disturbance force and torque. These disturbance terms are estimated using the finite-time stable disturbance observer in real-time and then compensated by the control scheme. The stability analysis for translational and rotational motions is carried out separately. It is shown that the discrete-time control laws achieve asymptotically stable tracking of the reference position and attitude trajectories.

Mesenchymal stromal cells (MSCs) isolated from various tissues are frequently used to expand hematopoietic stem/ progenitor cells (HSCs/HSPCs) in vitro. They are also co-infused with the HSCs to improve the HSC engraftment. However, the MSCs sourced from non-hematopoietic tissues could be less efficient in their hematopoiesis-supportive ability. Likewise, the hematopoiesis-supportive ability of the MSCs is known to decline after continuous in vitro culture – an unavoidable manipulation to get clinically relevant cell numbers. Hence, it may be necessary to boost the hematopoietic-supportive ability of the long-time cultured MSCs before their clinical applications in hematological disorders. In my earlier work, I showed that priming of MSCs isolated from human bone marrow (BMSC) with Transforming Growth Factor β1 (TGFβ1) boosts their hematopoiesis-supportive ability via activation of AKT-eNOS pathway. Accordingly, I also demonstrated that priming the BMSCs with nitric oxide (NO) donors mimics the effect of TGFβ1. Here I show that brief exposure of human BMSCs to pharmacological modulators of PKC and intracellular calcium – two downstream participants in the TGFβ1-eNOS signaling pathway – also boosts their hematopoiesis-supportive ability. Such an approach comprising priming the BMSCs with pharmacological compounds for a short duration and briefly exposing the HSCs to them can be used in clinical settings to improve the efficacy of stem cell transplantations. This concept would be helpful in other regenerative medicine protocols after identifying suitable pharmacological modulators giving desired effects on the target cells.

The integration of renewable energy resources and uncertainties in power system models pose significant challenges to load frequency control (LFC). To tackle these challenges, controller tuning with robustness constraints provides an efficient solution. In this paper, we propose a novel approach for controller tuning in LFC of microgrid systems with communication delay. Our approach converts the tuning task into an algorithm that solves two parametric equations subject to robustness constraints, resulting in high accuracy and computational efficiency. We use a perturbed scenario with uncertain microgrid model gains and communication delay to illustrate the tuning efficiency. Simulation examples, including comparisons with classical tuning methods, demonstrate the effectiveness of our proposed method.

Bitcoin has been evaluated as representing only a low money laundering threat. In numerous considerations, cryptocurrencies are seen as an unknown, marginal phenomenon restricted to the purview of experts Therefore, understanding the significance in the Arabic terms of maqasid syariah connected to determining the value of bitcoin in the hukmu al syarie is challenging especially via asynchronous classroom. This article is about the case study related; a) to explore the difficulty related to views of students at Pusat Kajian Syariah, UKM,  Bangi Malaysia in understanding the terms of Arabic Language in Maqasid Syariah via asynchronous classroom, and b) To explore views of students at Pusat Kajian Syariah, UKM,  Bangi Malaysia related to the needs of learning the Arabic terms related to Maqasid Syariah via asynchronous classroom. The results of this study suggest that other studies could be conducted in other domains related to bitcoin on a big scale for future research. The participants in the present study were reported to agree on the need in learning the Arabic terms related to maqasid syariah due to the significant use related to the complicated, limited knowledge of maqasid syariah and the category of either money or property. The findings of the study revealed that learners need to understand the Arabic terms related to maqasid syariah in learning Islamic Studies for comprehending their lesson simply. In asynchronous learning situation, the self-leaners have option to finish the learning session quickly with flexibilities but having problems in discussion with their friends.

Dispersal is a fundamental process in evolution and ecology. Due to the predominant role of flight in bird movement, their dispersal capabilities can be estimated from their flight morphology. Most predictors of flight efficiency require an estimate of the total wing area, but the existing methods for estimating wing area are multi-stepped and prone to compounding error. Here, we validated a new method for estimating the total wing area that requires only the measurement of the wingspan plus two measurements from the folded wings of study skin specimens: wing length and secondary length. We demonstrate that the new folded-wing method estimates total wing area with high precision across a variety of avian groups and wing shapes. In addition, the new method performs as well as the old method when used to estimate natal dispersal distances of North American birds. The folded-wing method will allow for estimates of the total wing to be readily obtained from thousands of specimens in ornithological collections, thus providing critical information for studies of flight and dispersal in birds.

Introduction: The T-cell subset (CD4+Tregs) play a significant role in immunoregulation, by active suppression of the immune system, through cell-to-cell contact and the secretion of IL10. The frequencies of these cell subpopulations were investigated in the mother. Methods: The study recruited 61 mothers out of this number, 31 mothers with plasmodium parasitized placentas and 30 mothers without plasmodium infection. Placental malaria positivity was determined by PCR and microscopy. Peripheral mononuclear cells (PBMCs) were isolated from peripheral blood, cultured in the presence of VAR2CSA antigen, and stained with antibodies (CD3, CD4, CD25, and IL-10), before cytometry analysis. Results: The CD4+CD25+ T cell frequencies were significantly higher in all the participants (p<0.0001), and comparable across gravida. These cell populations were similar when compared between primigravid and secumgravida mothers (p=0.77), and between multigravida and secumgravida mothers (p=0.84). Primigravid mothers with placental malaria had significantly higher frequencies of CD4+CD25+ T cell population (p=0.04). The frequencies of CD4+IL10 were significantly high in both primigravid and multigravid mothers who were placental malaria positive (p=0.03) and (p=0.04) respectively. Conclusion: Induced Tregs (CD4+IL10) cells could play a role in placental malaria susceptibility due to an increase in their populations in mothers with plasmodium-infected placentas.

Background Schistosoma spindale is a highly prevalent and pathogenic snail borne trematode of ruminants in the Indian subcontinent. The zoonotic significance of this parasite is associated with cercarial dermatitis in man. Human schistosome infection is infamous for its high morbidity and mortality rates and, animal schistosomosis adversely affects the livestock sector in endemic areas. Several protein candidates of schistosomes have been characterised to exploit the diagnostic and vaccine potential for the control of infection in man and animals, amongst which tegumental proteins have been found quite promising. However, such proteins of Indian schistsosome species have not been yet studied systematically. Objectives In this study, molecular characterisation of 14-3-3 tegumental protein encoding gene of S. spindale and in silico analysis of the predicted protein structure were done to assess its immunogenicity. Methods Kerala isolates of adult S. spindale worms were collected from mesentery samples, Total RNA was isolated and cDNA was synthesised from it. The synthesised cDNA was used as a template for the PCR amplification of the Ss14-3-3 gene and the confirmed amplicons were then column purified and bidirectionally sequenced using Sanger’s di-deoxynucleotide chain termination method. The sequences obtained were merged and subjected to further analysis using bioinformatic tools. Results A 759 bp amplicon of 14-3-3 tegumental protein encoding gene of S. spindale was translated into a protein sequence having 252 amino acids. The Ss14-3-3 nucleotide sequence showed the highest similarity of 94.99 per cent with S. bovis 14-3-3 zeta isoform mRNA. However, Ss14-3-3 protein sequence had the highest similarity with the 14-3-3 putative protein of S. mansoni (99.21 per cent). With the help of bioinformatic tools, it was concluded that the secondary and tertiary structures of this protein were stable and three potential B cell epitopes exists within the translated protein sequence. The protein was shown to possess structural stability and immunogenicity which makes it a potential immunogenic candidate against schistosomosis. Conclusions A 14-3-3 tegumental protein encoding gene of S. spindale was characterized for the first time. Sequence data was generated and in silico analysis revealed structural stability and possible immunogenicity. The study would serve as a platform to unravel the characteristics of tegumental proteins of animal schistosomes to be used in diagnostics and vaccines. However, further wet lab experiments including expression studies are necessary to validate these findings.

The energy consumption of cloud data centers is a critical concern that could affect both the environment and the availability of energy resources. For this, the global community and industries are taking measures to address this issue that is caused by the high electricity consumption of servers, Heating, Ventilation, and Air Conditioning (HVAC) in the data centers. With this context, this paper presents a novel approach for scheduling energy-efficient workflows (EEWS) in cloud computing using the MaxUtil model. The proposed approach incorporates the flower pollination algorithm (FPA), a popular meta-heuristic algorithm inspired by nature. The primary objectives of the proposed scheduling scheme are to minimize energy consumption and workflow processing time (makespan). The proposed algorithm involves two key phases: (i) assigning tasks to available virtual machines (VMs) and (ii) scheduling the tasks based on optimal criteria. As per our knowledge, this is the first study that focuses on optimizing energy consumption and makespan in cloud computing workflow scheduling using FPA. The proposed approch employs an effective representation of pollen and dynamic fitness function with multi-objective. The advantage of FPA lies in its speed of convergence and providing feasible solutions. Extensive studies have been conducted across five different scientific workflows from various fields. The proposed algorithm outperforms traditional workflow scheduling algorithms based on particle swarm optimization (PSO), gravitational search algorithms (GSA) and genetic algorithm (GA). The proposed algorithm outperforms GA, PSO, and GSA in the majority of cases, according to simulation findings. In addition, a well-known statistical test known as variance analysis (ANOVA) is used to validate the experimental results of the suggested algorithm. Based on the result’s of ANOVA test, the article claims that the suggested algorithm is superior to existing methods.

Cybersecurity is an ongoing and critical concern because of the constant and persistent threats from malicious actors such as hackers and crackers. The widespread use of software systems has revolutionized modern society in various aspects, but it has also brought forth new challenges in safeguarding sensitive and confidential information with the evolution of information and communication technology (ICT). Quantifying security measures can provide evidence to support decision-making in software security, especially when it comes to evaluating the security performance of software systems. This involves understanding the main quality criteria of security metrics, which can aid in building security metrology models based on practical requirements. To further explore this topic, this study conducted a systematic literature review of security metrics and measures in the context of Secure Software Development (SSD). The study selected 61 research studies based on specific inclusion and exclusion criteria and extracted data from the selected articles. The study identified 215 software security metrics, which were then categorized based on Software Development Life Cycle (SDLC) phases. To evaluate the effectiveness of the most commonly cited metrics in each phase, the study applied a SWOT analysis to highlight their strengths, weaknesses, opportunities, and threats. The findings of this study offer valuable guidance to diligent and motivated researchers to investigate emerging research trends and address existing gaps in Secure Software Development. Furthermore, this investigation provides software professionals with a more comprehensive understanding of security measurements, constraints, and open-ended specific and general issues.