Congenital Dyserythropoietic Anemia Type IV (CDA-IV) is still an emerging new disease with approximately 10 cases reported over the past three decades. CDA-IV is known to be caused by a specific mutation in exon 3 of KLF1, an erythroid transcription factor KLF1 with substitution of glutamic acid with lysine at residue 325 (KLF1 E325K). Because of the rarity of this disorder the presenting features are incompletely defined; especially the non-erythroid comorbidities. Here we report a new case, a male child, presenting with fetal hydrops and dysmorphic external genitalia.

Background and Purpose: Combination therapy has been widely recognized internationally, however, identifying drug combinations with synergism is very challenging. We first proposed a strategy for identifying drug combinations from herbs with mutual reinforcement or assistance in traditional Chinese medicine (TCM) formulae, and verified it using the example of Xijiao Dihuang Tang (XDT) , a classical TCM formula. Experimental Approach: In vitro the smallest half maximal inhibitory concentration (IC50) values of the candidate ingredients in XDT and synergistic neuroprotective effect of the drug combinationsin were studied in injured PC12 and BV2 cell by CCK8 and flow cytometry assay. The p38MAPK pathway affected by the drug combinations were predicted and validated using molecular docking method, biolayer interferometry, western blot and immunoprecipitation assessment. Antithrombotic of the drug combinations were evaluated in zebrafish thrombosis model in vivo. Results Two drug combinations with a combination index value of 0.1- 0.5 were obtained, indicating strong synergy. Our results suggested that, compared to the individual ingredients, the two drug combinations can strengthen the synergistic neuroprotective effects and have a significant antithrombotic effect, and not only enhanced the interaction with on MKK3, MKK6 and p38 in the p38MAPK pathway, but also interrupted the MKK3-p38 axis to inhibit MKK3-induced activation of p38 MAPK. Conclusions Our study identified two synergistic drug combinations as p38MAPK pathway inhibitors to develop antithrombotics and suggests that provide approaches and effective means for identifying drug combinations with synergism from the combination of herb-herb with mutual reinforcement or assistance in TCM formulae for drug combination development.

Title: ‘Hydropneumothorax as an Rare Manifestation of Secondary Hypereosinophilic Syndrome - A Case Report’Prakash Sapkota, Bhuwan Thapa, Aseem Bhattarai, Sujata Chalise, Sajana K C, Ashish TamangAbstract :We present a case of a young man who presented with cough and shortness of breath for two weeks with peripheral eosinophilia of unknown cause leading to left-sided pleural effusion. He was initially administered antiparasitic drugs (Ivermectin and Praziquantel). After one week the patient presented with an acute increase in SOB and was diagnosed with bilateral hydropneumothorax. A bilateral pigtail was inserted. Pleural fluid analysis was done which was purulent with lymphocyte predominance and high adenosine deaminase. The patient was treated with anti-tubercular therapy and steroids. After six months of therapy, the patient was asymptomatic. The hypereosinophilic syndrome can be presented in several ways and this study presented in a distinct way via hydropneumothorax.

Background: The effectiveness of eribulin and irinotecan in treatment of xenograft models of Ewing sarcoma is well-established but no clinical data has been reported. Methods: The medical records of patients treated for refractory or recurrent Ewing sarcoma with 1.4mg/m 2 D 1,8 eribulin and 20mg/m 2/d D 1-5,8-12 irinotecan at 21 day intervals (ERII) at Peking University People’s Hospital (PKUPH) were retrospectively reviewed. Results: A total of 17 patients with median age 18.6 years were treated with a total of 77 courses of ERII between February 2022 and February 2023. The objective response rate was 35.3%, disease control rate 58.9% and the median event-free survival (EFS) 2.07 months. 35.3% patients had 6 months EFS and overall survival was 66.9%. Grade 3 or 4 toxicities were observed in 37.6% courses and in 64.7% of the patients, with myelosuppression, especially neutropenia, being the most common and diarrhea / abdominal pain the second most common. Conclusions: The combination of eribulin and irinotecan as a second-line regimen is well-tolerated and shows promising efficacy. There is scope for further research into the synergistic mechanism of the two agents and into potential biomarkers.

Carbonate-rich soils limit plant performance and crop production. Previously, local adaptation to carbonated soils was detected in wild Arabidopsis thaliana accessions, allowing the selection of two demes with contrasting phenotypes: A1 (carbonate tolerant, c+) and T6 (carbonate sensitive, c-). Here, A1 (c+) and T6 (c-) seedlings were grown hydroponically under control (pH 5.9) and bicarbonate conditions (10 mM NaHCO 3, pH 8.3) to obtain ionomic profiles and conduct transcriptomic analysis. In parallel, A1 (c+) and T6 (c-) parental lines and their progeny were cultivated on carbonated soil to evaluate fitness and segregation patterns. To understand the genetic architecture beyond the contrasted phenotypes a bulk segregant analysis sequencing (BSA-Seq) was performed. Transcriptomics revealed 208 root and 2503 leaf differentially expressed genes (DEGs) in A1 (c+) vs T6 (c-) comparison under bicarbonate stress, mainly involved in iron, nitrogen and carbon metabolism, hormones, and glycosylates biosynthesis. Based on A1 (c+) and T6 (c-) genome contrasts and BSA-Seq analysis, 69 genes were associated with carbonate tolerance. Comparative analysis of genomics and transcriptomics discovered a final set of 18 genes involved in bicarbonate stress responses that may have relevant roles in soil carbonate tolerance.

Background Childhood and adolescent leukemia represent a significant disease burden worldwide, making research on leukemia in this population and its attributable risk factors highly valuable. The aim of this study is to estimate the burden of leukemia in children and adolescents, as well as the social-demographic status, for 21 regions around the world from 1990 to 2019. Methods We collected data of childhood and adolescent leukemia from the Global Burden of Disease (GBD) 2019 including, incidence, death, and Disability-adjusted life-years (DALYs). We also conducted an analysis of the Joinpoint model to estimate the time trend of incidence, death, and DALYs rate of leukemia. Results According to our analysis, the middle Socio-Demographic Index (SDI) experienced the highest decrease in incidence rate between 1990 and 2019, with an average annual percent change (AAPC) of -2.8* [95% CI, -3.0, -2.6]. On the other hand, the High-middle SDI witnessed the highest decrease in death rate, with an AAPC of -3.1* [95% CI, -3.30, -3.00].From 1990 to 2019, the incidence, mortality and DALYs of leukemia decreased by 51.46%, 53.87% and 54.46%, respectively, for both genders globally. We showed that DALYs of children leukemia is 155.98 (95%UI 127.18, 182.64) for global male, however, global female leukemia DALYs is 117.65(95%UI 102.07, 132.70). We also observed that in the two most representative regions of East Asia and Eastern Sub-Saharan Africa in 2019. Conclusions Despite the observed decline in the incidence, mortality, and DALYs of leukemia over the last three decades, the burden of childhood and adolescent leukemia remains high, particularly in areas with lower SDI.

Cyanobacterium Phormidium lacuna filaments move from dark to illuminated areas by twitching motility. Time-lapse recordings demonstrated that this photophobotaxis response was based on random movements with movement reversion at the light-dark border. The filaments in the illuminated area form a biofilm attached to the surface. The wild-type and two mutants, pixJ and cphA, were investigated for photophobotaxis at diverse wavelengths and intensities. CphA is a cyanobacterial phytochrome; PixJ is a biliprotein with a methyl-accepting chemotaxis domain and is regarded as a phototaxis photoreceptor. The cphA mutant exhibits reduced biofilm surface binding. The pixJ mutant was characterized by greater photophobotaxis sensitivity. Thus, PixJ is a negative photophobotaxis regulator and does not serve as a light direction sensor. 3-(3,4-dichlorophenyl)1,1-dimethylurea (DCMU) blocks electron transfer in PS II. At concentrations of 100 and 1000 µM DCMU, photophobotaxis was inhibited, whereas motility was not significantly affected. This specific effect indicates PS II’s central role in light-direction sensing. It is argued that the intracellular concentrations of regular photoreceptors, including CphA or PixJ, are too small for a filament to sense rapid light intensity changes in very weak light. Three arguments, specific inhibition by DCMU, broad spectral sensitivity, and sensitivity against weak light, support photosynthesis pigments use as photophobotaxis sensors.

Agriculture, is the predominant source of occupational or progression in India that ranges between 75 and 80 percentage of. After the production only based on agriculture. After the trauma and chaos of Second World War (1950-1960) every country concentrated to improve the agricultural farms, their production and value added agro produced. Human and animal resources are the mainly used during that tenure for versatile deeds of agriculture like ploughing, irrigation, weeding and harvesting. The dogs and bounds have been used to protect the cultivated crops and human houses. The industrial revolution paved a new opening in the agricultural verticals too since 1980. Machineries have been used for all sorts of agricultural activities from ploughing to honesty. After 2K centuries the agriculture systems are so much improved with smart agricultural technique and internet of things. Now a days used by various systematic approaches to improve the yield of the crops are with multiple times improved. But the yield of agriculture foods are poor quality and reduce the human lifetime because of modern agriculture systems. It used so much of newly invented medicines to the crop. Our proposed system is to concentrate the modern agriculture systems with old agricultural methods used to improve the quality and lifetime of a crop for producing natural foods are very useful to increase the human lifetime. The primary goal of the proposed system is to reduce manual labor and provide an innovative and convenient way to collect agricultural data. Various sensors like soil moisture sensor, air quality sensor, waterproof temperature sensor, humidity and temperature sensor etc., collect data from the farm field and the surrounding environment farming field. The farmers can prepare their garden/farm fields accordingly by analyzing these data. In the recent years, utilization of systematic approaches improves the yield of crops on Multifood.

The nervous system is central to coordinating behavioural responses to environmental change, likely including ocean acidification (OA). However, a clear understanding of neurobiological responses to OA is lacking, especially for marine invertebrates. We evaluated the transcriptomic response of the central nervous system (CNS) and eyes of the two-toned pygmy squid (Idiosepius pygmaeus) to OA conditions, using a de novo transcriptome assembly created with long read PacBio ISO-sequencing data. We then correlated patterns of gene expression with CO2 treatment levels and OA-affected behaviours in the same individuals. OA induced transcriptomic responses within the nervous system related to various different types of neurotransmission, neuroplasticity, immune function and oxidative stress. These molecular changes may contribute to OA-induced behavioural changes, as suggested by correlations between gene expression profiles, CO2 treatment and OA-affected behaviours. This study provides the first molecular insights into the neurobiological effects of OA on a cephalopod and correlates molecular changes with whole animal behavioural responses, helping to bridge the gap in our knowledge between environmental change and animal responses.

Heat flow is a geothermal parameter for indicating the heat sources distribution and evaluating geothermal reservoirs. Only 1230 heat flow points are distributed unevenly in China, mainly concentrated in the high-temperature geothermal areas and the southeast regions. The Songliao Basin is a potential geothermal field in China. Still, only 20 measurement points are known, making it difficult to evaluate the geothermal genetic mechanism. Sparse data interpolation using deep learning methods have high accuracy and are widely used in fields such as image processing. In this work, we propose a deep neural network for predicting heat flow in the Songliao Basin. More than 4,000 global heat flow and 23 geological and geophysical parameters are used as reference constraints for training. The uncertainty error of the prediction is estimated based on the correlation and distance-based generalized sensitivity analysis. The results show that the maximum heat flow is 85 mW/m2, the average is 67.1 mW/m2, and the error with the measured data is 10.64%. The previous geophysical and geological interpretation results indicate that the heat flow is higher in the west and lower in the east, with high anomalies in the central region, which may be related to the uplift of the deep mantle and the depression of the shallow low-velocity sedimentary layer. Some high-temperature melt bodies are in the deep layers, forming the current potential geothermal field. The measured data validates that the DNN is an effective method for predicting regional-scale heat flow, providing reliable heat source information for evaluating geothermal resources.

A document by wiem ben makhlouf. Click on the document to view its contents.

In this article, a model-free parallel reinforcement learning method is proposed to solve the suboptimal control problem for the Markov jump singularly perturbed systems. First, since fast and slow dynamics coexist in Markov jump singularly perturbed systems, it may lead to ill-conditioned numerical problems during the controller design process. Therefore, the original system can be decomposed into independent subsystems at different time-scales by employing the reduced order method. Besides, a model-based parallel algorithm is designed to obtain the optimal controllers of the fast and slow subsystems respectively. Moreover, within the framework of reinforcement learning, the composite controller of the Markov jump singularly perturbed systems can be obtained without system dynamics. Finally, a numerical example is introduced to prove the effectiveness of proposed algorithms.

Mechanistic and correlative models are two types of species distribution models (SDMs). They each have distinct foci, conceptual foundations, and levels of dependency on data availability, leading to potentially different estimates of species’ ecological niches and distributions. Mechanistic SDMs integrate detailed biological processes, making it possible to account for species’ biotic interactions. Despite their assumed importance, interactions in species distribution modeling remain uncommon. In this study, we applied an ensemble model of multiple correlative SDMs, a mechanistic SDM of the focal species (prey) alone, and a mechanistic SDM of the predator-prey interactions, to compare the predictions of correlative and mechanistic approaches and assess their relative strengths and limitations. We predict there are considerable and subtle differences in various predictions generated by the correlative and mechanistic approaches for each aphid species, which call for prior knowledge concerning species’ presence data or life histories. Our mechanistic SDMs allowed for the assessment of the relative significance of abiotic and biotic factors, along with their interactions, in determining species’ habitat suitability. Additionally, we predict aphid habitat suitability decreases across continents due to the effect of predation. However, this decrease may be offset or enhanced by the interaction effect between predation and climate change in different regions. This suggests the necessity of accounting for biotic interactions and the interplay between abiotic and biotic factors in mechanistic approaches. Our research highlights the impact of model philosophies in SDM studies and addresses the importance of selecting an appropriate modeling approach in line with the study’s objectives. Furthermore, our study suggests that mechanistic SDMs could serve as a valuable addition for assessing the robustness of correlative SDM predictions.

A document by Ahsen Shah. Click on the document to view its contents.

Airbone viral pathogens can rapidly spread and become a global menace, including both human and animal viruses which can trigger important socioeconomical and health effects. Therefore, to prevent and contain potential epidemic outbreaks, accurate, fast, and affordable diagnostic point-of-care tests (POCT) are required. As a proof of concept, we have developed a molecular detection system based in Loop-mediated isothermal AMPlification technique (LAMP) for two different RNA airborne viruses: the well-known human SARS-CoV-2, and the avian metapneumovirus (aMPV), the aetiologic agent of a communicable disease infecting mainly turkeys and chickens. To obtain a POC diagnostic system, we coupled the LAMP technique to DNA-functionalized gold nanoparticles detection. Validation of this system was carried out in 140 pharyngeal swabs from COVID-19 symptomatic and asymptomatic patients, and in 50 different samples (pharyngeal swabs and tracheal tissue samples) collected from aMPV infected chickens and turkeys. The system allows viral detection in about 60 minutes by the naked eye with 100% specificity, and 97.22% and 87.88% sensitivity for SARS-CoV-2 and aMPV, respectively. In summary, this novel detection system based on the coupling of RT-LAMP to DNA-nanoprobes allows suitable virus testing in the field, with accurate levels very close to conventional qRT-PCR based diagnosis.

Vinylene-linked covalent organic frameworks (COFs) have gained increasing attention for photocatalytic hydrogen evolution. However, the photocatalytic activity of vinylene-linked COFs has been restricted due to low exciton dissociation efficiency and wide band gap. Herein, we fabricated a novel p-n type Z-scheme heterostructure, g2T-T@HCOFs, through the hybridization of vinylene-linked COFs with a hollow structure and thiophene-based photosensitizer (g2T-T) using a template method and post-encapsulating modification. The hollow-structured HCOFs enable uniform encapsulation of the g2T-T both within their channels and on their surfaces, which facilitates the formation of a firm and stable interface between n-type HCOF and p-type g2T-T. Therefore, the encapsulation of g2T-T enables the realization of a Z-scheme pathway for efficient charge separation and transfer, leading to enhanced electron accumulation within the HCOFs during water splitting. Consequently, the obtained p-n type Z-scheme heterostructure g2T-T@HCOFs exhibit a remarkable 5.5-fold enhancement in visi-ble-light-induced hydrogen evolution activity compared to the pristine COF.

Phase-locked loop (PLL) technique is a critical control module applied in photovoltaic (PV) grid-connected control system to synchronize with grid voltage. The PLL error directly affects the response characteristic of PV grid-connected inverter under faults, leading to a mass of harmonic components in the output current of the PV inverter. Especially in the scenario of short-circuit fault with deep voltage sag, the PLL detection error is too significant to be ignored, posing challenges to transformer differential protection. This paper proposes an improved scheme that utilizes a digital computer algorithm to record and store pre-fault voltage, aiming to address the complexity and implementation challenges for phase-lock error in practical engineering applications. By utilizing the memory voltage, the PLL detection error is eliminated, mitigating harmonic distortion in the PV output current and ensuring the reliability of the transformer differential protection. However, introducing memory voltage may increase the short-circuit current of the PV output. Therefore, it is recommended to reduce the amplitude of the short-circuit current by multiplying the inverter port voltage reference value by an appropriate limiting coefficient k and outputting it to the physical system. Finally, the effectiveness of the proposed scheme is verified through MATLAB/Simulink simulation.

Centrifugal and shear forces are produced when solids or liquids rotate. Rotary systems and devices that use these forces, such as dynamic thin-film flow technology, are evolving continuously, improving material structure-property relationships at the nanoscale, representing a rapidly thriving and expanding field of research high with green chemistry metrics, consolidated at the inception of science. The vortex fluidic device (VFD) provides many advantages, with fluidic waves causing high shear and producing large surface areas for micro-mixing as well as rapid mass and heat transfer, enabling reactions beyond diffusion control in the processing. Combining these abilities allows for a green and innovative approach to altering materials for various research and industry applications by controlling small-scale flows and regulating molecular and macromolecular chemical reactivity, self-organization phenomena, and the synthesis of novel materials. This review highlights the aptitude of the VFD as clean technology, with an increase in efficiency for a diversity of top-down, bottom-up, and novel material transformations, benefiting from effective vortex-based processing for the transformation of material structure-property relationships.

Visual motion is ambiguous in that it can either represent object motion or self-motion. Visual-vestibular integration is most advantageous during self-motion. The current experiment tests the hypothesis that the visual motion needs to have a motion profile consistent with the inertial motion. To test this we compared the effect on heading perception when the visual stimulus was consistent with the inertial motion and compared this to the condition when the visual stimulus was inverted and was thus inconsistent with inertial motion. Twenty healthy human subjects (mean age 20 ± 3 years, 13 female) experienced 2 s of translation which they reported as left or right. A synchronized 2 s visual heading was offset by 0°, ±45°, ±60°, or ±75°. In randomly interleaved trials the visual motion was consistent with the inertial motion or inverted – it started at the peak velocity, decreased to zero mid-stimulus, then accelerated back to the peak velocity. When the velocity profile of the visual stimulus matched the velocity profile of inertial motion the inertial stimulus was biased 10.0 ± 1.8° (mean ± SE) with a 45° visual offset, 8.9 ± 1.7° with a 60° offset and 9.3° ± 2.5 ± with a 75° offset. When the visual stimulus was inverted so it was inconsistent with the inertial motion the respective biases were 6.5 ± 1.5°, 5.6 ± 1.7°, and 5.9 ± 2.0°. Thus, the biases with the inverted stimulus were significantly smaller (p < 0.0001), demonstrating that visual motion profile is consider in multisensory integration.

The loss of wildlife species due to habitat deterioration and pollution represents the major threats to biodiversity conservation. This is compounded by the rapid development of infrastructure i.e., the expansion of roads, railways, harbours; construction of industries, human settlements and agricultural infrastructure. A few studies have explored the significant effects of emerging infrastructure development on wildlife species and habitats particularly in developing countries like Tanzania. We reviewed 58 research articles and reports, to highlight the significant impacts of emerging infrastructure on both aquatic and terrestrial species and habitats in Tanzania. We show that despite the role it plays to the development, the infrastructure contributes significantly to the loss of wildlife species. For instance, avoidance, habitat loss, edge effects incursion, population, isolation, road mortality, and increased human access are among the effects of highway across the Serengeti, Mikumi, and Katavi National parks in Tanzania. Effect of on health of aquatic species, pollution and loss of habitat have been pointed out as impacts due to construction of hotels and industries upstream and along the coasts, expansion of harbours and agricultural activities. Environment effects i.e., reduction of forest, ecosystem services, and riverine habitat, loss of species are anticipated due to the construction of Stiegler’s Gorge Hydroelectric Dam, across the Rufiji River in eastern Tanzania. Though infrastructure development undoubtedly offers opportunities to boost economic growth and reduce poverty in developing nations, it should be planned to have the least possible negative effects on biodiversity. Well–planned infrastructure development could lessen human pressure on wildlife species and habitats. This paper would be useful to policymakers and politicians in developing nations to avoid implementing infrastructure in biodiversity–rich or protected areas as their decision may jeopardize the integrity of wildlife species and future generations.

Background: Approximately 50–90% of children with immediate-type cow’s milk allergy (CMA) acquire tolerance by pre-school age. We aimed to investigate the tolerance acquisition rate of CMA in children aged 6–12 years. Methods: Children with CMA that persisted until 6 years of age were included. Tolerance acquisition was defined as either passing an oral food challenge with 200 mL of unheated cow’s milk (CM) or consuming CM of any quantity without symptoms. Persistent CMA was defined as fulfilling neither of these criteria by 12 years of age. Children undergoing oral immunotherapy were defined as having persistent CMA. Risk factors associated with persistent CMA were assessed using Cox regression analysis. Results: Of the 123 children analyzed, 60 (49%) had previous CM anaphylaxis, 82 (67%) eliminated CM from their diet, and the median CM-specific immunoglobulin E (sIgE) level was 23.3 kU A/L at 6 years of age. Twenty-five children (20%) acquired tolerance by 9 years of age, and 46 (37%) by age 12. At baseline, higher CM-sIgE levels (hazard ratio: 2.58 [95% confidence interval: 1.62–4.12], optimal cutoff level: 34.4 kU A/L), previous CM anaphylaxis (2.42 [1.24–4.69]), and complete CM elimination (5.18 [2.45–10.99]) were associated with persistent CMA. None of the children with CMA who had all three risk factors (n = 26) acquired tolerance. Conclusion: At least one-third of the children with CMA at 6 years of age acquired tolerance by 12 years of age. Children with CMA who have the risk factors are less likely to acquire tolerance.

A document by Nuriye Korkmaz. Click on the document to view its contents.

Clinical excellence is the ability to provide rigorous, evidence-based, and rewarding care to the right patients. The BALM (brilliance, attitude, leadership, and materials) framework is a novel model for adjudicating clinical excellence. There are a few models and frameworks for evaluating clinical excellence, but each has its flaws and does not consider the peculiarities of economically-challenged regions such as sub-Saharan Africa. Coincidentally, such low-resource areas have an urgent need for a framework to assess clinical excellence because of their low health-related indices. The five-step mode of professional excellence is a well-recognised tool and was the model upon which the BALM framework was built. So, the BALM framework determines to what extent, using the five-step stages of novice, advanced beginner, competent, proficient, and expert, a clinician has achieved in each of the four critical domains, namely brilliance, attitude, leadership and materials. Therefore, a clinician, who strives for excellence, aims to be an “expert” in each of the domains of the BALM framework. The framework is concise, practical, easy to use, and multidimensional, although it still needs to be applied widely to assess its reproducibility.

We study the small initial data Cauchy problem for the three-dimensional Boussinesq equations with the Coriolis force in variable exponent Fourier-Besov spaces. By using the Fourier localization argument and Littlewood-Paley decomposition, we obtain the global well-posedness result for small initial data (u 0,θ 0) belonging to the critical variable exponent Fourier-Besov spaces $\mathcal{F}\mathcal{\dot{B}}_{p(\cdot),q}^{2-\frac{3}{p(\cdot)}}$.