The comparison of three types of ionosonde data from Europe during an Interplanetary Coronal Mass Ejection (ICME) and a Stream Interaction Regions (SIRs) / Corotating Interaction Regions (CIRs) -driven geomagnetic storm event is detailed in this study. The selected events are 16-20 March 2015 for the ICME-driven and 30 May to 04 June 2013 for the SIR/CIR-driven one. Ionospheric data from three European ionosonde stations, namely Pruhonice (PQ), Sopron (SO) and Rome (RO), are investigated. The ionospheric F2-layer responses to these geomagnetic events are analyzed with the ionospheric foF2 and h’F2 parameter, the calculated deltafoF2 and deltahF2 values, ratio of Total Electron Content (rTEC) and Thermosphere, Ionosphere, Mesosphere, Energetics and Dynamics (TIMED) satellite Global Ultraviolet Imager (GUVI) thermospheric [O]/[N2] measurement data. The storm-time and the quiet day mean values are also compared, and it can be concluded that the quiet day curves are similar at all stations while the storm-time ones showed the latitudinal dependence during the development of the storm. As a result of the electron density comparison, during the two events it can be concluded that SSC that characterized the ICME induced a Travelling Atmospheric Disturbance (TAD) seen in the European stations, while this is not in the SIR/CIR-driven ionospheric storm, which showed a stronger and more prolonged negative effect in all stations probably due to the season.

A joint analysis of solar wind, geomagnetic field, and earthquake catalog data showed that before the catastrophic M7.8 and M7.5 Kahramanmaras earthquake sequence on February 6, 2023, the closed strong magnetic storm occurred on November 7, 2022, SYM/H=-117 nT. Storm started at 08:04 UT. At this time, the high latitudinal part of Turkey's longitudinal region of future epicenters was located under the polar cusp, where the solar wind plasma would directly access the Earth's environment. The time delay between storm onset and earthquake occurrence was ~91 days. We analyzed all seven strong (M7+) earthquakes from 1967 to 2020 to verify the initial findings. A similar pattern has been revealed for all events. The time delay between magnetic storm onset and earthquake occurrence varies from some days to some months. To continue these investigations, a retrospective analysis of seismic and other geophysical parameters just after preceded geomagnetic storms in the epicenter areas is desirable.

Background: Robot-assisted laparoscopic surgery robot-assisted surgical system has gained significant popularity over open and laparoscopic interventions. However, given its high costs, it remains unclear what clinical advantages robot-assisted laparoscopic surgery offers over conventional laparoscopic surgery. Objective: This umbrella review aims to synthesize and compare the clinical outcomes of robot-assisted laparoscopic surgery versus conventional laparoscopic surgery for five surgical procedures. Inclusion criteria: All systematic reviews and meta-analyses published in the past five years that compared the clinical outcomes of conventional laparoscopic surgery and robot-assisted laparoscopic surgery for cholecystectomy, colectomy, hysterectomy, nephrectomy and/or prostatectomy were included. Methods: A systematic literature search was conducted in PubMed and Scopus. The quality of all included reviews was assessed with the AMSTAR 2 quality assessment tool. Each review’s study characteristics (and a list of primary sources) were extracted, along with the quantitative and qualitative data for the following ten clinical outcomes: blood loss, rate of conversion to open surgery, hospitalization costs, incisional hernia rate, intraoperative complication rate, postoperative complication rate, length of hospital stay, operative time, readmission rate and wound infection rate. Results: Fifty-two systematic reviews and (network) meta-analyses were included in this umbrella review, covering more than 1,288,425 patients from 1046 primary sources published between 1996 and 2022. The overall quality of the included reviews was assessed to be low or critically low. Robot-assisted laparoscopic surgery yielded comparable results as conventional laparoscopic surgery in terms of blood loss, conversion to open surgery rate, intraoperative complication rate, postoperative complication rate, readmission rate and wound infection rate for most surgical procedures. While the hospitalization costs of robot-assisted laparoscopic surgery were higher and the operative times of robot-assisted laparoscopic surgery were longer than conventional laparoscopic surgery, robot-assisted laparoscopic surgery reduced the length of hospital stay of patients in nearly all cases. Conclusion: Robot-assisted laparoscopic surgery achieved comparable results with conventional laparoscopic surgery for cholecystectomy, colectomy, hysterectomy, nephrectomy and prostatectomy based on ten clinical outcomes. Further research is needed to prove that robot-assisted laparoscopy is as safe and reliable as conventional laparoscopic surgery.

Integrated information theory (IIT) proposes a measure of integrated information (Φ) to capture the level of consciousness for a physical system in a given state. Unfortunately, calculating Φ itself is currently only possible for very small model systems, and far from computable for the kinds of systems typically associated with consciousness (brains). Here, we consider several proposed measures and computational approximations, some of which can be applied to larger systems, and test if they correlate well with Φ. While these measures and approximations capture intuitions underlying IIT and some have had success in practical applications, it has not been shown that they actually quantify the type of integrated information specified by the latest version of IIT. In this study, we evaluated these approximations and heuristic measures, based not on practical or clinical considerations, but rather based on how well they estimate the Φ values of model systems. To do this, we simulated networks consisting of 3–6 binary linear threshold nodes randomly connected with excitatory and inhibitory connections. For each system, we then constructed the system’s state transition probability matrix (TPM), as well as its state transition matrix (STM) over time for all possible initial states. From these matrices, we calculated, approximations to Φ, and measures based on state differentiation, state entropy, state uniqueness, and integrated information. All measures were correlated with Φ in a state dependent and state independent manner. Our findings suggest that Φ can be approximated closely in small binary systems by using one or more of the readily available approximations (r > 0.95), but without major reductions in computational demands. Furthermore, Φ correlated strongly with measures of signal complexity (LZ, r_s = 0.722), decoder based integrated information (Φ*, r_s = 0.816), and state differentiation (D1, r_s = 0.827), on the system level (state independent). These measures could allow for efficient estimation of Φ on a group level, or as accurate predictors of low, but not high, Φ systems. While it’s uncertain whether the results extend to larger systems or systems with other dynamics, we stress the importance that measures aimed at being practical alternatives to Φ are at a minimum rigorously tested in an environment where the ground truth can be established.

To address the issue of reduced orbit estimation accuracy resulting from discrepancies between in-orbit measured geomagnetic field values and IGRF model values in autonomous orbit estimation of microsatellites based on geomagnetic field measurements, this study introduces an adaptive cubature H-infinity filtering algorithm. Firstly, it presents the low-altitude orbital dynamics model and geomagnetic field measurement model for microsatellites. Subsequently, within the adaptive cubature H-infinity filtering algorithm, a spherical simplex rule and a second-order Gaussian-Legendre quadrature criterion are employed to compute the spherical surface integral and radial integral. Additionally, a spherical simplex-radial quadrature rule is proposed to enhance the approximation accuracy of nonlinear Gaussian weighted integrals. Furthermore, by integrating extended H-infinity filtering based on game theory with the cubature quadrature rule, an inverse proportional relationship between constraint level and filtering innovation is established. This allows for adaptive adjustment of the constraint level to enhance robustness against model errors. Finally, through semi-physical simulation experiments, it is demonstrated that compared with traditional algorithms, the proposed algorithm improves autonomous orbit estimation position accuracy of microsatellites by 7.49%, while also enhancing velocity accuracy by 3.1%, thus validating its effectiveness.

When working with the novel coronavirus SARS-CoV-2 during a pandemic response, having a rapid, reproducible and reliable assay for infectious virus quantitation and utilization for evaluation of potential therapeutics is critical. Compared to traditional agarose overlay plaques visualized with neutral red, assays performed with Avicel R RC-591 semi-solid overlay provide a simplified format for rapid and easy detection and neutralization testing. The method is easily modified for higher throughput using dispensers or automated processing. Fixation using formalin provides flexibility when dealing with pathogenic agents such as SARS-CoV-2 where tissue culture plates might be removed from biocontainment for staining. Although plaque assays are considered straightforward in principle, having an easily reproducible, consistent plaque assay is an invaluable tool.

The integration of magnetic observatories of many countries into the Intermagnet network has provided researchers with new opportunities to investigate many geophysical processes. The joint processing of measurement evidence from magnetic observatories located in various geolocations makes it possible to better understand the dynamics of the interaction of solar plasma fluxes with the Earth's magnetosphere. For the correct interpretation of the dynamics of physical processes, the accuracy of the time reference of measurement results is of great importance. The measurement results of local observatories were transformed to a unified ecliptic coordinate system oriented towards the Sun in order to extract small variations in the magnetic field occurring before the magnetic storm commencement. Before transforming the coordinates, a constant component equal to the average daily value of the magnetic field components was removed from the results of minute-by-minute measurements. Owing to the averaging evidence from 84 magnetic observatories of the Intermagnet network, variations in the magnetic field of cosmic origin, preceding the magnetic storm commencement were detected. The correlation analysis of these variations recorded by different observatories revealed the presence of time shifts between the data series of different observatories. Only 62% of the observatories had a relative data shift within the range of ± 1 minute. Before the joint data processing in order to efficient use of data recorded with a time shift a method for correcting time shifts has proposed.

Geomagnetic induced current (GIC) is a ground end manifestation associated with the space weather perturbations that should be greatly taken into account by the society. Although the GICs implication to the power system is not regular, it can cause large scale of system failure. In equatorial, the power system is considered safe since the most intense of geomagnetic storm happened in high latitude. However, the internal damage due to GICs which finally led to the South African power system failure has totally changed the normal perception. Therefore, a preliminary investigation on the GICs activity in equatorial region is performed to understand the space weather impact to the power system. Time derivative of the horizontal magnetic field component (dB/dt) is done to indicate the GICs activity value based on Faraday’s law. All the reported power failures are compiled to produce the threshold value of dB/dt, which possibly cause the harmful effect to the system. Then, dB/dt analysis is extended to show the pattern of GICs activity in function of magnetic latitude and local time. The results reveal that power network in equatorial region has possibly suffered by GIC. Plus, high number of intense GIC activity in this region occurred during dayside.

The month of May 2024 was characterized by solar energetic particles events directed towards the Earth, especially the big event causing a strong terrestrial geomagnetic storm during the night from 10 to 11 May 2024, with auroras observed everywhere in Europe. This was the strongest storm for the last 20 years with a Dst < -400 nT. In the present work, we show with observations of GOES, PROBA-V/EPT and MetOP/MEPED that this exceptional event was associated with the injection of energetic protons in the proton radiation belt, with important consequences for the South part of the South Atlantic Anomaly (SAA). In addition, the geomagnetic storm caused by the solar eruption has had tremendous impacts on the electron radiation belts. Indeed, we show that for 0.3 to 1 MeV electrons, the storm led to a long lasting four belts configuration which was not observed before with EPT launched in 2013, until a smaller geomagnetic storm on June 15 took place. Moreover, for the first time since its launch, observations of the EPT show that ultra-relativistic electrons with E>2 MeV have been injected into the inner belt until L=2.4, violating the impenetrable barrier previously estimated to be located at L=2.8.

A typhoon-induced storm surge is considered one of the most severe coastal disasters in Taiwan. However, the combination of the storm surge and the astronomical tide called the storm tide can actually cause extreme flooding in coastal areas. This study implemented a two-dimensional hydrodynamic model to account for the interaction between tides and storm surges on the coast of Taiwan. The model was validated with observed water levels at Sauo Fish Port, Hualien Port, and Chenggong Fish Port under different historical typhoon events. The model results are in reasonable agreement with the measured data. The validated model was then used to evaluate the effects of the typhoon's intensity, bathymetric change, and the combination of the typhoon’s intensity and bathymetric change on the maximum storm tide and its distribution along the east coast of Taiwan. The results indicated that the maximum storm tide rises to 1.92 m under a typhoon with an intensity of a 100-year return period. The maximum storm tide increased from a baseline of 1.26 m to 2.63 m for a 90% bathymetric rise at Sauo Fish Port under the conditions of Typhoon Jangmi (2008). The combination of the intensity of a typhoon with a 100-year return period and a 90% bathymetric rise will result in a maximum storm tide exceeding 4 m, 2 m, and 3 m at Sauo Fish Port, Hualien Port, and Chenggong Fish Port, respectively. We also found that the distribution of the maximum storm tide on the east coast of Taiwan can expand significantly subject to the bathymetric rise.

An ionospheric response at middle latitudes to geomagnetic storms is not yet very well understood. Total electron content (TEC) variations associated with eight strong geomagnetic storms between 2015 and 2022 obtained from GNSS receivers in the western area of the North Atlantic (Portuguese continental and insular territory) are studied in an attempt to fill this gap. It was found that for most of the studied geomagnetic storms TEC variations are synchronous for the longitudinal ranges from 27ºW and 9ºW. In the southern part of the studied region (around 32ºN) the amplitude of TEC variations is, in general, significantly higher than in the northern part (around 39ºN). Some of the studied geomagnetic storms were associated with TEC variations that we interpret as effects of post-sunset equatorial plasma bubbles that travelled well north from their habitual region. Also, while most of the studied storms were accompanied by reports on different kind of malfunction of GNSS systems (GPS; GALILEO and other), there is no clear pattern in their appearance in dependence on the geomagnetic/ionospheric storms’ strength, commencement time, and its characteristics, in general.

Pediatric onset multiple sclerosis (POMS), characterized by the onset of multiple sclerosis before the age of 18, is gaining increased recognition. Approximately 5 percent of MS cases manifest before the age of 18, with less than 1 percent occurring before the age of 10. Despite its rarity, pediatric MS exhibits distinct characteristics, with an association between younger age at onset and a comparatively slower disease progression. Despite this slower progression, individuals with POMS historically reach disability milestones at earlier ages than those with adult-onset multiple sclerosis. While various immunomodulatory agents demonstrate significant benefits in MS treatment, such as reduced relapse rates and slower accumulation of brain lesions on magnetic resonance imaging (MRI), the majority of disease-modifying therapies (DMTs) commonly used in adult MS lack evaluation through pediatric clinical trials. Current evidence is predominantly derived from observational studies. This comprehensive review aims to consolidate existing knowledge on the mechanisms of action, efficacy, safety profiles, and recommended dosages of available DMTs specifically in the context of pediatric MS. Furthermore, the review outlines recent advancements and explores potential medications still in developmental stages, providing a thorough overview of the current landscape and future prospects for treating POMS.

In this study, we performed periodicity analyzes of selected daily solar (FI, CI), geomagnetic (Ap, Dst, Scalar B) and cosmic (CRI) activity indices for the last solar Cycle 24 (December 2008 to December 2019). To investigate the periodic variations of above selected data sets the Multi Taper Method (MTM), Morlet wavelet, Cross Wavelet Transform (XWT), and Wavelet Coherence (WTC) analysis techniques were used. In results of our analysis we found that i) the 25-33 and 2048-day periodicities exist in all data sets without any exception, while all other detected periodicities have data preferences, ii) all detected periods located around the maximum phase of the cycle (Cycle 24), iii) the phase relations between compared data sets periodicities are gradually changing from small periods to large ones; there are no phase relations between small periodicities and they show mixed phases, while they are completely in phase/antiphase for large periodicities, iv) all detected FI periodicities, except 2048 days periodicity, are common periodicities with all other data sets used in this study.

This study investigates the impact of geomagnetic storms that occurred on June 8, 22-23, and 25, 2015, on the ionosphere in the low-latitude and equatorial regions of Brazil. By examining various data sources, such as solar wind parameters from the ACE satellite, GPS vertical total electron content (VTEC), magnetometer data, and the SAMI2 model, we aimed to simulate the effects of storms on the ionosphere in these regions. Two methods were employed to separate DP2 and Disturbance dynamo (Ddyn) from the ionospheric disturbance current (Diono). Our analysis revealed a positive (negative) ionospheric storm in the VTEC during the main phase (recovery) of the June 22-23 and 25 storms. This observation can be attributed to the combined impact of the eastward prompt penetration of the magnetospheric convection electric field (westward disturbance dynamo electric field) and changes in the storm-time thermospheric [O]/[N_2] ratio based on the GUVI satellite imagery. Notably, the westward disturbance dynamo exhibited a significant amplitude on June 23 in Belem. The amplitude of the D_dyn at Belem (dip lat: - 0.47˚) was greater than that at Alta Floresta (dip lat: - 3.75˚) due to intensified cowling conductivity in Belem. Furthermore, we found that the SAMI2 model provided more accurate results when we replaced the default ExB drift with the vertical drift calculated from the ground-based magnetometer, enabling us to simulate the effect of the westward DDEF on VTEC during daytime.

Urea cycle disorders (UCDs) are common inborn errors of metabolism, with an incidence of one in 30,000 births. They are caused by deficiencies in any of six enzymes and two carrier proteins, the most common being Ornithine Transcarbamylase Deficiency (OTCD). OTCD results in impairment to excrete nitrogen, causing toxic buildup of ammonia with resultant encephalopathy. Hyperammonemia (HA) induces the conversion of glutamate to glutamine in the brain. Excess glutamine in the brain causes osmotic changes cerebral edema, changes in astrocyte morphology, and cell death. Acute symptoms of HA include vomiting, hyperventilation, seizures, and irritability. Long-term neurological changes include deficits in working memory and executive function. To date, there are no predictors of prognosis of infants with neonatal onset OTCD outside of plasma ammonia level at presentation and duration of hyperammonemic coma. We provide a comprehensive analysis of a 16-year-old male with neonatal onset of OTCD as an example of how brain biomarkers may be useful to monitor disease course and outcome. This male presented at 8 days post natal with plasma ammonia and glutamine of 677 and 4024 micromol/L and had a missense mutation in Exon 4 (p.R129H). Treatment included protein restriction, sodium benzoate, and citrulline, arginine, and iron. He suffered recurrent acute hyperammonemic episodes despite compliance, triggered by infections or catabolic stressors. We discuss the long-term effects of the hyperammonemic episodes by following MRI based disease biomarkers.

The most prevalent musculoskeletal disorder of childhood with unclear aetiology is Growing Pains (GPs). Anatomic deformities and factors that change bone turnover are implicated in GPs pathophysiology. Perinatal risk factors alter the bone metabolism affecting the bone mineral density and content. The aim of our study was to analyze the relationship between GPs, knock knees and perinatal factors. The examined population consisted of 276 children aged 3-7 years. Among them 10 pairs of dizygotic twins were evaluated. The data were collected by using a combination of semi-structured questionnaires, clinical examinations and medical charts of the children and the obstetric history of the mothers. 78 children presented GPs meeting Peterson’s criteria. Genu valgum severity was a significant factor for GPs manifestation and for their increased frequency and intensity. Subsequently, perinatal factors regarding gestational age, Apgar score, head circumference (lower than 33cm) and birth length or weight (smaller than 50 cm and 3000gr, respectively) made a remarkable contribution to the development of GPs. Conversely, antenatal corticosteroid treatment, increased maternal age and maternal smoking during pregnancy were not predictive for the disorder. Our data are potentially supportive for the “bone strength” theory and for the contribution of anatomical disturbances in GPs appearance.

With the urgent need of precise positioning faced by internet of things (IoT) applications, the universality and cost of indoor positioning devices become key factors. Since the 5G network has been widely deployed, new opportunity is brought by tightly fusing the traditional low-cost sensors, i.e., the magnetometer. In this study, using 5G channel state information (CSI) and geomagnetic data, a multi-input convolutional neural network (CNN) localization system was proposed. First, to generate a data tensor that is easy for CNN processing, the raw data was reconstructed individually. Then, to comprehensively incorporate the features of 5G CSI and geomagnetic strength data, the ReLU function was chosen as the activation function of the convolutional layer. After that, a multi-input CNN was trained using the incorporated geomagnetic strength and CSI amplitude in the off-line side, and the trained CNN was recorded as a location fingerprint, which can be used for the user position prediction. Finally, in the online side and using a multi-input CNN, the 2-D coordinates are estimated and tested indoors in a typical conference room scenario. The results showed that longer sampling time of fingerprint data result in better uniqueness of the reference point, while the data collection time of locating points does not need to be long. Taking the positioning efficiency and accuracy into consideration, a sampling time of 3s at the reference point and 0.2s at the locating point are recommended. The positioning accuracy using the proposed method was 1.41 m, with an improvement of 22.9% compared with the 5G positioning, and an improvement of 18.0% compared with the 5G and geomagnetic fusing positioning using single CNN.

Approximately 20% of patients with colorectal cancer (CRC) are diagnosed with a mucinous subtype of this tumor, have a worse prognosis, and often show resistance to available therapies. Molecules from the mucin family are involved in the regulation of epithelial-mesenchymal transition (EMT), which significantly determines the cancer aggressiveness. This study aimed to examine the diagnostic and prognostic significance of mucinous histology and EMT markers in patients with early-onset CRC and their association with disease severity and tumor characteristics. The study included tumor tissue samples from 106 patients diagnosed with CRC before the age of 45, 53 with mucinous and 53 with non-mucinous tumors. The EMT status was determined by immunohistochemical analysis of E-cadherin and Vimentin in tissue sections. Mucinous tumors had a significantly higher cytoplasmic E-cadherin score (P=0.043), they were significantly less differentiated (P=0.007), more advanced (P=0.005), and predominately affected right colon (P=0.030) in comparison to non-mucinous tumors. Epithelial tumors were significantly better differentiated (P=0.034) and with less prominent tumor budding (P < 0.001) than mesenchymal tumors. The process of EMT appears to be more prominent in tumors of younger patients regardless of mucinous histology. EMT status may represent a useful prognostic tool in early-onset CRC.

Abstract: Congenital hyperinsulinism (CHI) is a rare disorder of glucose metabolism and is the most common cause of severe and persistent hypoglycemia (hyperinsulinemic hypoglycemia, HH) in the neonatal period and childhood. Most cases are caused by mutations in the ABCC8 and KCNJ11 genes that encode the ATP-sensitive potassium channel (KATP). We present the correlation between genetic heterogeneity and the variable phenotype in patients with early-onset hyperinsulinemic hypoglycemia caused by ABCC8 gene mutations. In the first patients, which presented persistent severe hypoglycemia since the first day of life, molecular genetic testing revealed the presence of a homozygous mutation in the ABCC8 gene [deletion in the ABCC8 gene c.(2390+1_2391-1)_(3329+1_3330- 1)del] correlated with a diffuse form of hyperinsulinism (the parents being healthy heterozygous carriers). In the second patient, the onset was on the third day of life with severe hypoglycemia, and genetic testing identified a heterozygous mutation in the ABCC8 gene c.1792C&gt;T (p.Arg598*) inherited on the paternal line, which led to the diagnosis of focal form of hyperinsulinism. To locate the focal lesions, (18)F-DOPA (3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine) PET/CT was recommended (an investigation that cannot be carried out in the country), but the parents refused to carry out the investigation abroad. In this case, early surgical treatment could have been curative. In addition, the second child also presented secondary adrenal insufficiency requiring replacement therapy. At the same time, she developed early recurrent seizures that required antiepileptic treatment. We emphasize the importance and of molecular genetic testing for diagnosis, management and genetic counseling in patients with HH.

An earthquake of Mw6.4 hit the coastal zone of Albania on 26 November 2019, at 02:54:11 UTC. It was intensively felt at about 34km far away, in Tirana City, where damages and lives lost occurred. To emphasize a geomagnetic signature before the onset of this earthquake, the data collected on the interval 15 October–30 November 2019, at the Panagjurishte (PAG)-Bulgaria and Surlari (SUA)-Romania observatories are analyzed by using both the polarization parameter (BPOL)-time invariant in non-seismic conditions, becoming unstable before this seismic event, and the strain effect for geomagnetic signal identification. Consequently, BPOL time series and its standard deviations are performed for the both sites using ULF-FFT band-pass filtering. A statistical analysis, based on a standardized random variable equation, was applied to emphasize on the BPOL*(PAG) and ABS BPOL*(PAG) time series the anomalous signal’s singularity and, to differentiate the transient local anomalies due to Mw6.4earthquake, from the internal and external parts of the geomagnetic field, taken PAG observatory as reference. Finally, the ABS BPOL*(PAG-SUA) time series are obtained on the interval 1-30 November, 2019, where a geomagnetic signature greater than 2.0, was detected on 23 November and the lead time was 3 days before the onset of Mw6.4earthquake.

The storm of November 12th-13th, 2019 provoked the displacements of boulders in a central Mediterranean rocky coast; with reference to a selected area, prone to the boulder production and geomorphologically monitored for years, a field-oriented study approach was applied for the phenomenon, by collating data concerning pre-storm locations and kinematics of these boulders. The number of displaced boulders is 11, that is, in terms of morphological imprint of a specific storm, one of the major study cases for the Mediterranean. In addition, based on widely used hydrodynamic equations, the minimum wave height required to displace the boulders is assessed. The values conform with the expected values for the wave climate dominating during the causative meteorological event and give a measure of the energy of the storm slamming the coast. Boulder dislodgements usually have plays a key role in determining the rate of the coastal recession, likely also in the investigated area. In view of an adverse climate evolution with a possible increase of energy and frequency of severe storms, the results deriving from the study of this morphodynamics should be considered for the hazard assessment and coastal management.

Objectives: To investigate the etiology of amyotrophic lateral sclerosis (ALS) in an adult female patient. Methods: We conducted trio genome sequencing on a 35-year-old woman with progressive weakness in her left upper limb, as well as on her parents. Prior to sequencing, we performed a comprehensive neurological work-up on the patient, including neurological exam, electrophysiology, biomarker assessment, and brain and spinal cord MRI. Results : The propositus experienced weakness and atrophy in her left hand 6 months before the evaluation. This was associated with brisk reflexes and Hoffman sign in the same arm. Electroneuromyography revealed lower motor neuron involvement in three body regions. Neurofilament light chains were elevated in her cerebrospinal fluid. Brain imaging showed asymmetrical T2 hyperintensity of the corticospinal tracts and T2 linear hypointensity of the precentral gyri. Genome trio sequencing identified a likely pathogenic de novo variant in the propositus’s KIF1A gene (NM_001244008.2): c.574A&gt;G, p.(Ile192Val). Discussion: Pathogenic variants in the KIF1A gene have been associated with a wide range of neurological manifestations called KIF1A-associated neurological diseases (KAND). The present report describe a likely pathogenic de novo variant in KIF1A associated with ALS, expanding the phenotypic spectrum of KAND and our understanding of the pathophysiology of ALS.

Introduction: Lipoyl transferase 2 is involved in biosynthesis of the lipoate. Lipoate is the cofactor for the glycine cleavage system and four dehydrogenase enzymes. Biallelic variants in LIPT2 causing severe neonatal encephalopathy was first described in 2017. Methods: Clinical data was collected by retrospective chart review after obtaining consent from parents. The pathogenicity of these variants was further delineated using a yeast model. The YEp352-LIPT2 plasmid was used as a template to generate the two patient variants using QuickChange Lightning Site-Directed Mutagenesis Kit. Results: Patient was a 15-month-old female who presented at 1 month with dystonia, developmental delay and feeding difficulties. MR Brain showed cortical malformations including colpocephaly, polymicrogyria and heterotopia. Patient had elevations in lactate (6.1 mmol/L) and glycine. Exome sequencing showed 2 variants of uncertain significance in trans in the LIPT2 gene: c.346 G>T and c.418C>T. Patient was started on lipoic acid, thiamine and COQ10. Yeast complementation experiments indicate that both patient mutation variants result in diminished function versions of the LIPT2 protein. Conclusion: We report the fourth case of LIPT2-related disorder. Proband shared significant overlap with previous patients, however had a distinct movement disorder and brain malformations which have not been previously described. Unlike most neurometabolic disorders where dystonia develops later after metabolic stroke in basal ganglia, LIPT2- related disorder seems unique due to early onset of dystonia due to energy deficit in the developing brain. Lipoic acid supplementation has not led to significant clinical improvement. Analyses in yeast indicate that novel variants are deleterious but have retained some functionality.

The fractal dimension of geomagnetic variations at the Baigazan magnetic station at Russian Altay for 2011-2013 was calculated using the Higuchi method. The daily variation of Higuchi Fractal Dimension (HFD) for the D,H,Z-components of the geomagnetic field has been investigated, its contribution to the variability of HFD is from 30 to 40 percent of the total variance. A correlation analysis of the fractal dimension of the variations of the D,H,Z-components with Auroral Electrojet (AE) index and solar wind characteristics was carried out. A negative correlations with logarithms of AE-index, interplanetary magnetic field (IMF) strength and solar wind velocity were found. About 25 percent of the fractal dimension variance is controlled by the variability of these characteristics. Pair and partial correlation coefficients for these parameters were calculated for every month of 2011-2013.

One of the main problems is handling rainwater management in urban areas is water quality from urban run-off. Currently, the emphasis is on using rainwater in cities as much as possible. The concentration of pollutants is the most problematic in rainwater. After precipitation falls on surfaces, surface water is immediately contaminated. This pollution must be cleaned or contained and transported to a wastewater treatment plant through the sewer network. Among the primary pollutants that we can identify in surface water are, for example, heavy metals. In our research, we focus on the analysis of real surface waters taken from 13 lo-cations on the territory of the Slovak Republic. The result of the research is an analysis of the suitability of reusing these waters. From the results of the analyses, it is clear that not a single sample is suitable for irrigation, as the limits of at least one monitored parameter were exceeded in all samples. The monitored lead concentration parameter was exceeded in all monitored samples.

Underwater wireless optical communications (UWOC) have attracted considerable attention in recent years as an alternative means for acoustic communication. However, optical path loss of light propagation from attenuation is large due to absorption and scattering in various water conditions. Identification of environmental effects especially tropical storms on underwater optical path loss is the key to the success of using optics for UWOC. Underwater inherent optical properties (IOPs) such as the beam attenuation coefficient for 470 nm light in the western North Pacific Ocean were measured from the U.S. Naval Oceanographic Office sea gliders with being deployed after Super Typhoon Guchol (7-20 June 2012)‘s passage during 25-30 June 2012 and no any typhoon passage during 9 January – 28 February 2014. The observed two sets (with and without super typhoon) of IOPs are taken as input into a recently developed Radiative Transfer Equation solver. The simulated normalized received powers for the two durations show large impact of typhoon passage on UWOC.

The dysregulated release of cytokines has been identified as one of the key factors behind poorer outcomes in COVID-19. This ‘cytokine storm ‘produces an excessive inflammatory and immune response, especially in the lungs, leading to acute respiratory distress (ARDS), pulmonary edema and multi-organ failure. Alleviating this inflammatory state is crucial to improve prognosis. Pro-inflammatory factors play a central role in COVID-19 severity, especially in patients with comorbidities In these situations, an overactive, untreated immune response can be deadly, suggesting that mortality in COVID-19 cases is likely due to this virally driven hyperinflammation. Administering immunomodulators has not yielded conclusive improvements in other pathologies characterized by dysregulated inflammation such as sepsis, SARS-CoV-1 and MERS. The success of these drugs at reducing COVID-19-driven inflammation is still anecdotal and comes with serious risks. It is also imperative to screen the elderly for risk factors that predispose them to severe COVID-19. Immunosenescence and comorbidities should be taken into consideration. In this review, we summarize the latest data available about the role of the cytokine storm in COVID-19 disease severity as well as potential therapeutic approaches to ameliorate it. We also examine the role of inflammation in other diseases often comorbid with COVID-19, such as aging, sepsis, and pulmonary disorders. Finally, we identify gaps in our knowledge and suggest priorities for future research aimed at stratifying patients according to risk as well as personalizing therapies in the context of COVID19-driven hyperinflammation.

Sars-CoV-2 outbreak represents a public health emergency, affecting different regions of the world. Lung is the organ more damaged due to the high presence of Sars-CoV-2 binding receptor ACE2 on epithelial alveolar cells. Severity of infection vary from absence of symptomatology to be more severe, characterized by acute respiratory distress syndrome (ARDS), multiorgan failure and sepsis requiring treatment in Intensive Care Unit (ICU).It is not still clear why in a small percentage of patients immune system is not able to efficiently suppress viral replication. It has been documented as predictive factors for severity and susceptibility affections of cardiovascular system such as heart failure (HF), coronary heart disease (CHD) and risk factors for atherosclerotic progression, hypertension and diabetes among others.Atherosclerotic progression, as chronic inflammation process, is characterized by immune system dysregulation leading to pro-inflammatory pattern, including (Interleukin 6) IL-6, Tumor Necrosis Factor α (TNF-α) and IL-1β raise. Reviewing immune system and inflammation profiles in atherosclerosis and laboratory results report in severe Sars-CoV-2 infection we have supposed a pathogenetic correlation. Atherosclerosis may be a pathogenetic ideal substrate to high viral replication ability leading to adverse outcomes, how reported in patients with cardiovascular factors. Moreover, level of atherosclerotic progression may impact on a different degree of severe infection and in a vicious circle feeding itself Sars-CoV-2 may exacerbate atherosclerotic progression due to excessive and aberrant plasmatic concentration of cytokines.

New onset diabetes mellitus after transplantation (NODAT) is a common complication following solid organ transplantation, with varying incidence rates due to discrepancies in defining NODAT and follow-up duration, alongside modifiable and non-modifiable risk factors. NODAT adversely affects patient survival and graft longevity, warranting early detection, especially in countries experiencing a rise in kidney transplant cases, emphasizing the need for understanding diagnostic criteria, risk factors, pathogenic mechanisms, and post-transplant outcomes.

The paper presents a study of two novel visual motion onset stimulus-based brain–computer interfaces (vmoBCI). Two settings are compared with afferent and efferent to a computer screen center motion patterns. Online vmoBCI experiments are conducted in an oddball event–related potential (ERP) paradigm allowing for “aha–responses” decoding in EEG brainwaves. A subsequent stepwise linear discriminant analysis classification (swLDA) classification accuracy comparison is discussed based on two inter–stimulus–interval (ISI) settings of 700 and 150 ms in two online vmoBCI applications with six and eight command settings. A research hypothesis of classification accuracy non–significant differences with various ISIs is confirmed based on the two settings of 700 ms and 150 ms, as well as with various numbers of ERP response averaging scenarios.The efferent in respect to display center visual motion patterns allowed for a faster interfacing and thus they are recommended as more suitable for the no–eye–movements requiring visual BCIs.

Early diagnosis of paroxysmal atrial fibrillation (PAF) could suggest patients to receive timely interventions in clinical practice. Various PAF onset prediction algorithms might benefit from accurate heart rate variability (HRV) analysis and machine learning classification but to be challenged in real-time monitoring scenarios. The aim of this study is to present an end-to-end deep learning based PAFNet model that integrates a sliding window technique on raw R-R interval of electrocardiogram (ECG) segments to achieve a real-time prediction of PAF onsets. This integration enable the deep convolutional neural network (CNN) to be customized as a light-weight architecture that accommodates the size of sliding windows simply by altering the input layer, specifically its effectiveness in making a new prediction with each new heartbeat. Catering to potential influence of input sizes, three CNN models were trained using 50, 100, and 200 R-R intervals, respectively. For each model, the performance of automated algorithms was evaluated for PAF prediction using a ten-fold cross-validation. As a results, a total of 56,381 PAFN-type and 56,900 N-type R-R interval segments was collected from publicly accessible ECG databases, and a promising prediction performance of the automated algorithm with a 100 R-R intervals was achieved in terms of the sensitivity of 97.12%, the specificity of 97.77%, and the accuracy of 97.45%, respectively. Importantly, the automated algorithm with a sliding windows step of 1 could process one sample in only 23.1 milliseconds and identify the onset of PAF at least 45 minutes in advance. The present results suggest that the sliding window technique on raw R-R interval sequences along by deep learning based algorithms may offers the possibility of providing an accurate, real-time, and end-to-end clinical tool for mass monitoring of PAF.

A very strong earthquake of magnitude Mw8.2 struck the coastal zone of Alaska (USA), on July 29, 2021. This earthquake was felt around the Gulf of Alaska, on a wide offshore area belonging to USA and Canada. In order to identify an anomalous geomagnetic signal before the onset of this earthquake, we retrospectively analyzed the data collected on the interval June 17 - July 31, 2021, via internet (www.intermagnet.org), at the two geomagnetic observatories, College (CMO) - Alaska and Newport (NEW)-USA, by using the polarization parameter (BPOL) and the strain effect–related to geomagnetic signal identification. Thus, for the both observation sites (CMO and NEW), the daily mean distribution of the BPOL and its standard deviation (STDEV) are carried out using an FFT band-pass filtering in the ULF range (0.001-0.0083Hz). Further on, a statistical analysis based on a standardized random variable equation was applied to emphasize the following: a) the anomalous signature related to Mw8.2 earthquake on the both time series BPOL*(CMO) and BPOL*(NEW); b) the differentiation of the transient local anomalies associated with Mw8.2 earthquake from the internal and external parts of the geomagnetic field, taking the NEW observatory as reference. Finally, on the BPOL*(NEW-CMO) time series, carried out on the interval 07-31 July, 2021, a very clear anomaly of maximum, greater than 1.2 STDEV, was detected on July 22, with 7 days before the onset of Mw8.2 earthquake

Tropical storm Nate, which was a powerful hurricane prior to landfall along the Alabama coast, traversed north towards our instrumented site in Hunstville, AL. The rain bands lasted 18 h and the 2D-video disdrometer (2DVD) captured the event which was shallow and indicative of pure warm rain processes. Measurements of raindrop size, shape and velocity distributions are quite rare in pure warm rain and are expected to differ from cold rain processes. In particular, asymmetric shapes due to drop oscillations and their impact on polarimetric radar signatures in warm rain have not been studied so far. Recently, the 2DVD data has been used for 3D reconstruction of asymmetric raindrop shapes but their fraction (relative to the more common oblate shapes) in warm rain has yet to be ascertained. Here we compute the scattering matrix drop-by-drop using Computer Simulation Technology integral equation solver for drop sizes>2.5 mm. From the scattering matrix elements, the polarimetric radar observables are simulated by integrating over 1 minute consecutive segments of the event. These simulated values are compared with dual-polarized C-band radar data located at 15 km range from the 2DVD site to evaluate the contribution of the asymmetric drop shapes.

Background: Long-range transport of dust aerosol has intense impacts on the atmospheric environment over wide areas. Methods: The annual and seasonal changes in meteorological parameters associated with the occurrence of dust storms were studied. The features of an intense dust storm and its transport characteristics were studied during June 7th to June 9th 2010 in Ahvaz city. Temporal and spatial distribution of Middle Eastern dust storm event was analyzed by models of HYSPLIT and WRF/Chem, and in- situ observations. Results: A disagreement between the occurrences of dust storms, temperature, relative humidity and rainfall, show the major source of dust storms over Ahvaz city are neighboring countries. Using HYSPLIT results, the dust particles are mainly transported from north western region of Iraq and eastern Syria to downward areas including Ahvaz city. The arrived Dust aerosols mixed with local anthropogenic emissions, led to the highest PM10 concentration of 4200 ppm. The model results were found to well reproduce temporal and spatial distribution of mineral dust concentrations according to in-situ measurements. Conclusion: The performance of WRF/Chem was acceptable for simulation of temporal and spatial distributions of dust storm events. Therefore, it can be taken as a reference in daily air quality forecasting.

COVID-19 patients suffer from detrimental effects of cytokine storm and not much success has been achieved to overcome this issue. We sought to test the ability of selenium in reducing the impact of two important cytokine storm players; IL-6 and TNF-a. The effects of four selenium compounds were evaluated on the secretion of these cytokines from THP-1 macrophages in vitro following LPS challenge. Also, potential impact of methylseleninic acid (MSeA) on Nrf2 and IkBa was determined following short treatment of THP-1 macrophages. MSeA was observed to be the most potent selenium form to reduce IL-6 and TNF-a levels among the four selenium compounds tested. In addition, an increase in Nrf2 and decrease in pIkBa in human macrophages was observed following MSeA treatment. Our data indicate that COVID-19 patients might benefit by suppressing their cytokine storm with addition of MSeA to the standard therapy.

Recently, the intensities of natural disasters have increased significantly owing to climate change and various other environmental factors, causing unprecedented damage. Measures must be established to reduce damage from large-scale natural disasters caused by the rapidly changing environment. The Japanese government published a hazard map manual in 2015 and obligates the creation of a hazard map as a measure to reduce high-scale storm surges. This manual presents a typhoon model based on a parametric model that is used to create a hazard map. The Myers model assuming concentric circles, which is primarily used in East Asia, is disadvantageous as it cannot consider geographic characteristics. Therefore, a new parametric model is necessary to calculate wind and pressure fields, which change according to geographic characteristics. To improve this limitation of the Myers model, we calculated the wind and pressure fields considering geographical effects by combining the Holland model, which can consider the size of a developing typhoon, and the Mascon model, which changes by geographic characteristics. To determine the gradient coefficient of the Holland model, the coefficient that changes every moment was calculated using grid point value data. The result indicated excellent reproducibility of storm surge height according to the geographic characteristics.

The Lower Rio Grande Valley, South Texas is considered one of the more vulnerable coastal areas to flooding related with abrupt climate changes. From 1980-2017, there were 7 flooding events, 57 severe storm events, and 8 tropical cyclone events with losses exceeding $1 billion in the State of Texas, according to NOAA NCEI. Coastal flooding is typically a result of storm surge and heavy rainfall produced by hurricanes and tropical storms. In this study, the two-dimensional hydrodynamic flow circulation model is developed to predict the Lower Rio Grande Valley coastal area inundation due to the hurricane storm surge, especially in the case of Hurricane Beulah, 1967. The tropical cyclone properties and tidal constituents were assigned to the updated watershed geographic information with the bottom bathymetric and roughness data. For model validation, the Hurricane Dolly 2008 storm surge due to Hurricane Beulah at the coast and the storm surge reaches up to approximately 40 kilometers west from the coast through a natural river channel. This model can be used for a reliable engineering tool for the coastal hazard emergency management and disaster mitigation.

Recent epidemiologic studies have revealed an upward trend in young-onset colorectal cancer (YOCRC) overall, whereas specific data on young-onset colorectal neuroendocrine neoplasms (YONEN) remain limited. This study investigates demographic characteristics and survival trends in YONEN and compares these with those of young-onset colorectal adenocarcinoma (YOADC), the most common histologic subtype of YOCRC. A retrospective analysis was conducted from 2000 to 2019 using the Surveillance, Epidemiology, and End Results (SEER) database. Survival outcomes were assessed using univariate and multivariable Cox proportional models, with demographic differences evaluated via Wilcoxon Rank Sum and Chi-square tests. Out of 61,705 patients aged 20-49 with colorectal cancer, 8% had NEN, and 92% had adenocarcinoma. The YONEN cohort had a higher proportion of Black patients and a lower proportion of White patients than the YOADC cohort (21% vs. 13% and 44% vs. 57%, respectively). NEN was more commonly found in the rectum (79%), and adenocarcinoma was mostly colonic (57%) in origin. YONEN patients had better survival than YOADC patients. Multivariate analysis in YONEN patients revealed that Hispanic patients had better overall survival compared to White patients (HR 0.67, 95% CI 0.47-0.95, p=0.024). Racial disparities should be investigated further to aid in policymaking and targeted interventions.

Background/Objectives: Obstructive Sleep Apnoea Syndrome (OSA) in children disrupts standard breathing patterns and sleep architecture, potentially leading to severe consequences. Early identification and intervention for OSA are crucial to prevent these issues. This study explored the relationships between waiting times for polysomnography (PSG), clinical history, age at the time of PSG, and PSG outcomes in children; Methods: Two hundred and fourteen children were prospectively enrolled. Data were extracted from medical records on the age at referral for PSG and at the time of its execution, the waiting time for PSG, diagnosis (primary snoring, mild, moderate, and severe OSA), history of snoring and apnoea, medications taken, surgical interventions, passive smoke exposure, and allergies. The records also included the Pediatric Sleep Questionnaire (PSQ); Results: The mean age at referral for PSG was 5.2 (2.8) years, the waiting time for PSG was 5.2 (5.0) months, and the age at the time of PSG was 5.6 (2.8) years. Children with a shorter history of OSA (≤12 months) underwent PSG at an earlier age (4.9 (2.7) years) compared to those with a more extended history (6.0 (2.7) years; p=0.006). A younger age at referral for PSG was associated with a lower PSQ score (r=0.167; p=0.015), a shorter history of apnoea (r=0.216; p=0.003) and snoring (r=0.187; p=0.023), but also with greater OSA severity, expressed as oxygen desaturation index (r=-0.152; p=0.026). In the correlation analysis, the waiting time for PSG, adjusted for age at referral, was longer in children with a prolonged history of apnoea (r=0.195; p=0.023) and snoring (r=0.259; p=0.002) but with a lower PSQ score (r=-0.172; p=0.045); Conclusions: Some children receive delayed treatment, increasing the risk of long-term complications. In evaluating children with suspected OSA, the duration of symptoms and the PSQ score at referral emerge as crucial factors that should be considered to optimise prioritisation for PSG access.

In chronic myeloid leukemia (CML), a clonal proliferative disorder of granulocytic lineage, the 90%‐95% of cases are characterized by t(9;22) (q34.1;q11.2) translocation, leading to the Philadelphia chromosome (1). Rarely, CML patients directly present a blast crisis, mostly of myeloid origin (2, 3). Herein, we describe one rare CML case, showing an unusual early T lymphoid blastic crisis.

Mosquitoes are responsible for the transmission of numerous pathogens, including Plasmodium parasites, arboviruses and filarial worms. They pose a significant risk to public health with over 200 million cases of malaria per annum and approximately four billion people at risk of arthropod-borne viruses (arboviruses). Mosquito populations are geographically expanding into temperate regions and their distribution is predicted to continue increasing. Mosquito symbionts, including fungi, bacteria and viruses, have desirable traits for mosquito disease control including spreading horizontally and vertically through mosquito populations and potentially colonising multiple important vector species. Paratransgenesis, genetic modification of mosquito symbionts with effectors to target the pathogen rather than the vector, is a promising strategy to prevent the spread of mosquito-borne diseases. A variety of effectors can be expressed but venom toxins are excellent effector candidates because they are target specific, potent, and, stable. However, the only toxins to be explored in mosquito paratransgenesis to date are Scorpine and mutated phospholipase A2. To enhance the scope, effectiveness, and durability of paratransgenesis, an expanded arsenal of effectors is required. This review discusses other potential toxins effectors for future paratransgenesis studies based on prior in vitro and in vivo antiparasitic and antiviral studies and highlights the need for further research and investment in this area. In terms of mosquito-borne diseases, paratransgenesis strategies have been developed to target Plasmodium. We postulate the potential to apply this principle to target arboviruses using antiviral toxin effectors.

There is limited data on pregnancy outcomes in Pompe Disease (PD) resulting from deficiency of the lysosomal enzyme acid alpha-glucosidase. Late-onset PD is characterized by progressive proximal muscle weakness and decline of respiratory function secondary to the involvement of the respiratory muscles. In a cohort of twenty-five females, the effects of both PD on the course of pregnancy and the effects of pregnancy on PD were investigated. Reproductive history, course of pregnancy, use of Enzyme replacement therapy (ERT), PD symptoms, and outcomes of each pregnancy were obtained through a questionnaire. Among 20 subjects that reported one or more pregnancies, one subject conceived while on ERT and continued therapy through two normal pregnancies with worsening of weakness during pregnancy and improvement postpartum. While fertility was not affected, pregnancy may worsen symptoms, or cause initial symptoms to arise. Complications with pregnancy or birth were not higher, except for an increase in the rate of stillbirths (3.8% compared to the national average of 0.2-0.7%). Given small sample size and possible bias of respondents being only women who have been pregnant, further data may be needed to better analyze the effects of pregnancy on PD, and the effects of ERT on pregnancy outcomes.

The national study analyzes sea level rise (SLR) impacts based on 36 different SLR and storm surge scenarios across 5.7 million geographic locations and 3 time periods. Taking an approach based on engineering design guidelines and current cost estimates, the study details projected cost impacts for states, counties, and cities. These impacts are presented from multiple perspectives including total cost, cost per-capita, and cost per-square mile. The purpose of the study is to identify specific locations where infrastructure is vulnerable to rising sea levels. The study finds that Sea Level Rise (SLR) and minimal storm surge is a $400 billion threat to the United States by 2040 that includes a need for at least 50,000 miles of protective barriers. The research is limited in its scope to protecting coastal infrastructure with sea walls. Additional methods exist and may be appropriate in individual situations. The study is original in that it is a national effort to identify infrastructure that is vulnerable as well as the cost associated with protecting this infrastructure.

This paper investigates the characteristics and impact of a major Saharan dust storm during June 14^th -19^th 2020 to atmospheric radiative and thermodynamics properties over the Atlantic Ocean. The event witnessed the highest ever aerosol optical depth (close to 2 during the peak of the storm) for June since 2002. The satellites and high-resolution model reanalysis products well captured the origin, spread and the effects of the dust storm. The Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) profiles, lower angstrom exponent values (~ 0.12) and higher aerosol index value (> 4) tracked the presence of elevated dust. It was found that the dust AOD was as much as 250-300% higher than their climatology resulting in an atmospheric radiative forcing ~200% larger. As a result, elevated warming ( 8-16 %) was observed, followed by a drop in relative humidity(2-4%) in the atmospheric column, as evidenced by both in-situ and satellite measurements. Quantifications such as these for extreme dust events provide significant insights that may help in understanding their climate effects, including improvements to dust simulations using chemistry-climate models

Background: Meniere disease (MD) is an inner ear disorder associated with comorbidities such as autoimmune diseases or migraine. This study describes clinical and cytokine profile in MD according to the age of onset of the condition. Methods: A cross-sectional study including 83 MD patients: 44 with early onset MD (EOMD, <35 years old), and 39 with late onset MD (LOMD, > 50 years old), 64 patients with migraine and 55 controls was carried out. Clinical variables and cytokines levels of CCL3, CCL4, CCL18, CCL22, CXCL1 and IL-1β were compared among the different groups. Results: CCL18 levels were higher in patients with migraine or MD than in controls. Elevated levels of IL-1β were observed in 11.4% EOMD and in 10.3% LOMD patients and these levels were not dependent on the age of individuals. EOMD had a longer duration of the disease (p=0.004) and a higher prevalence of migraine than LOMD (p=0.045). Conclusions: Patients with EOMD have a higher prevalence of migraine than LOMD, but migraine is not associated with any cytokine profile in patients with MD. The levels of CCL18, CCL3 and CXCL4 were different between patients with MD or migraine and controls.

Inflammatory allergic and nonallergic respiratory pathologies often co-exist. The root cause is not clear. This paper demonstrates that it is ascribable to protons (H⁺) released into cells by exogenous and endogenous acids. The hypothesis of acids as the common cause stems from two considerations: a) it has long been known that exogenous acids present in air pollutants can induce the irritation of epithelial surfaces, particularly the airways, inflammation and bronchospasm; b) according to recent articles, endogenous acids, generated in cells by phospholipases, play a key role in the biochemical mechanisms of initiation and progression of allergic responses. Therefore, the intracellular acidification and consequent Ca²⁺ increase, induced by protons generated by either acid pollutants or endogenous phospholipases, may be the causal mechanism of the multimorbidity of these diseases, and environmental acidity may contribute to their spread.

Although cardiac resynchronization therapy (CRT) reduces morbidity and mortality and reverses left ventricular (LV) remodeling in heart failure patients with LV electrical dyssynchrony, induced proarrhythmia has been reported. The mechanism of CRT-induced proarrhythmia remains under debate. In this case report, a description of how a LV pacing induced polymorphic ventricular tachycardia immediately after the initiation of CRT has been reported. Changing the pacing configuration using a multipoint pacing stimulation, we can assume that VTs induced are related to the reentry mechanism facilitated by the unidirectional block. As a result, MPP pacing configuration near the scar area avoid the onset of a unidirectional block with the establishment of the reentry phenomenon thus avoiding induced VTs.

Objectives: In December 2019 a novel human-infecting coronavirus, SARS-CoV-2, has emerged. The WHO has stated the epidemic as a “public health emergency of international concern”. A drammatic situation has emerged with thousands of deaths, occurring mainly in the aged and very ill people. Epidemiological studies suggest that immune system function is impaired in elderly individuals and these subjects often present a severe deficiency in nutrients as fatsoluble and hydrosoluble vitamins. Design: In this first part of the review about Cov2 in aged people, we searched for reviews describing the characteristics of autoimmune diseases and the available therapeutic protocols for their treatment. We sed them as a paradigm with the purpose to retrieve pathogenetic mechanisms in common among these pathological conditions and SARS-CoV-2 infection, as well as the alteration induced in immune system function by this virus, or by its homologous SARS-CoV. Results: SARS-CoV-2 infection induces an important immune system dysfunction with the development of an exhuberant proinflammatory response in the host, and with the development of a life-threatening condition defined as Cytokine Release Syndrome (CRS). This leads to the Acute Respiratory Syndrome (ARDS), mainly in the aged people. High mortality and lethality rates have been observed in the elderly subjects with CoV-2-related infection. Conclusion: These diseases may serve as a paradigm for the study of CRS emerging in the course of SARS CoV-2 infection. This review discusses about the possible activity of Vitamin A, D, E and C in restoring normal antiviral Immune System function or the potential therapeutic role of these micronutrients as a part of a multi-treatment strategy against SARS- CoV-2 infection.

Late-onset Alzheimer’s disease (LOAD) is a dementia category disease that starts after the age of 65. Progressive problems in thinking, behaviour, learning etc. are its characteristics. Due to its progressive nature, early diagnosis is crucial. A complex pathway mechanism with different risk factors is involved in LOAD progression. A comprehensive study is done on factors causing LOAD, biomarkers used for diagnosis in clinical and preclinical stage of the disease, ML (Machine Learning) techniques to identify disease stage. We reviewed research papers on clinical and preclinical diagnosis of LOAD using ML techniques from biomarker data: MRI, PET image, MMSE, Genome / Gene expression, DNA / RNA binding sites with protein, Epigenetic expression /DNA, methylation, Speech and text. We have listed improvement scope after finding the gaps and scope of using Generative AI and SMOTE (Synthetic Minority Oversampling Technique) for data augmentation. At the end, we have elaborated current use of DL (Deep Learning) and CNN (‘Convolution Neural Network’) in Alzheimer’s disease (AD) diagnosis.

Alzheimer’s disease (AD) predominantly occurs as a late-onset form (LOAD), involving neurodegeneration and cognitive decline with progressive memory loss. Over time, risk factors and aging promote accumulation of well-known AD pathologies in oxidative stress, amyloid-beta and tau protein pathology, as well as inflammation. Homeostatic glial functions regulate and suppress these AD pathologies; however, other glial states involve increased pro-inflammatory cytokine release and further pathology accumulation. Different stresses can additionally induce cellular senescence, or an irreversible differentiation process resulting in decreased supportive functions and increased, pro-inflammatory cytokine release. While these pathophysiological underpinnings all contribute to LOAD, they require temporal and mechanistic integration. This perspective hypothesizes that when individuals have threshold senescent glia accumulation, they transition from healthy cognition into mild cognitive impairment and LOAD diagnosis. Particularly, senescent microglia are predicted to represent a final threshold required for the tau pathology burden and spreading that corresponds to sustained neurodegeneration and dementia severity. We first explore age-related decline in glia that promote increases in AD pathologies, and then discuss emerging evidence linking oxidative stress, neurons containing tau pathology, and amyloid-beta to microglia, oligodendrocyte progenitor cell, and astrocyte senescence. Our hypothesis proposes that senescent astrocytes and oligodendrocyte progenitors pressure microglia to phagocytose neurons containing tau pathology. The resulting senescent microglia would form neuritic plaques and induce paracrine senescence transitioning into a progressive clinical dementia presentation. This predictive hypothesis can potentially account for why medications used to treat LOAD fail, as previous treatments have not reduced senescent glial burden. It is also coherent with the predominant hypotheses surrounding LOAD, generates testable hypotheses about LOAD, and increases rationale in testing senolytics as targeted treatments for LOAD arrest and reversal.

The storm 'Daniel' has caused the most severe flood phenomenon that Greece has ever experienced, with thousands of hectares of farmland submerged for days. This led to sediment deposition in the inundated areas, which significantly altered the chemical properties of the soil, as revealed by extensive soil sampling and laboratory analysis. Causal relationships between soil chemical properties and sediment deposition were extracted using the DirectLiNGAM algorithm. Results of causality analysis showed that the sediment deposition affected the CaCO3 concentration in the soil. Also, causal relationships were identified between CaCO3 and available phosphorus (P-Olsen), as well as between sediment deposit depth and available manganese. The quantified relationships between the soil variables were then used to generate data using a Multiple Linear Perceptron (MLP) regressor for various levels of deposit depth (0, 5, 10, 15, 20, 25 and 30 cm). Then linear regression equations were fitted across the different levels of deposit depth to determine the effect of deposit depth on CaCO3, P, and Mn. The results show that there is a linear slope of 0.12, -0.16, and 0.13, for CaCO3, P, and Mn with deposit depth, respectively. Statistical analysis indicates that corn growing in soils with sediment over 10 cm requires a 31.8% increase in P rate to prevent yield decline. Additional notifications regarding cropping strategies in the near future are also discussed.

Storm Ophelia made landfall over Ireland as an extra-tropical storm on the morning of the 16th of October 2017. The storm caused major power outages, lifted roofs, caused coastal flooding in Ireland, and resulted in the loss of three lives. A model’s capability to forecast extreme weather events such as Storm Ophelia is of utmost importance and now with a changing climate, it becomes more important to improve and enhance model forecasting capability. The Weather Research and Forecasting (WRF) model V3.9 has been configured for the Irish domain and this study presents a preliminary evaluation of the Model during Storm Ophelia. Simulated wind speed and direction were compared with hourly remote sensing (lidar) and in-situ (wind speed and wind direction at 10m) observations at the coastal site of Mace Head Atmospheric Research Station on the West coast of Ireland (53.33◦ N, 9.90 49 ◦ W). The model simulation has generally small biases in the simulated wind speed and wind direction during this case study. The model also realistically simulated the magnitude and geographical distribution of the wind speed and wind direction observed during Ophelia.

Practitioners who assess the risk associated with urban trees often factor in the presence or absence of visual tree defects when determining whether a tree may fail. While these defects are a main fixture in many tree risk assessment systems and best management practices, the research supporting their usefulness in predicting tree failure during storms is limited. When looking at past research involving populations of storm-damaged trees, there are several defects that have never predicted failure (or have been associated with reduced rates of failure). In this study, we took a closer look at four such defects: codominant branches; branch unions with included bark; multiple stems originating from the same point; and overextended branches. After Hurricane Ian, we revisited 1519 risk assessed trees where one of these four defects was identified as the primary condition of concern. Fourteen of these trees experienced branch failure during the storm (which hit the study area as a downgraded tropical storm). Upon closer inspection, none of these failures occurred at the defect of concern. Our findings indicate that none of the defects assessed appeared to increase the likelihood of tree failure in the species tested. Our results are in line with past research on these defects derived from post-storm assessments and analysis.

Background: Cytokine storm in COVID-19 is heterogenous. There are at least three subtypes: cytokine release syndrome (CRS), macrophage activation syndrome (MAS), and sepsis. Methods: A retrospective study comprising 276 patients with SARS-CoV-2 pneumonia. All patients were tested for ferritin, interleukin-6, D-Dimer, fibrinogen, calcitonin, and C-reactive protein. According to the diagnostic criteria, three groups of patients with different subtypes of cytokine storm syndrome were identified: MAS, CRS or sepsis. In each group, treatment results were assessed depending on whether or not tocilizumab was used. Results: MAS was diagnosed in 9.1% of the patients examined, CRS in 81.8%, and sepsis in 9.1%. Median serum ferritin in patients with MAS was significantly higher (5894 vs. 984 vs. 957 ng/ml, p &lt;0.001) than in those with CRS or sepsis. Hypofibrinogenemia and pancytopenia were also observed in MAS patients. In CRS patients, a higher mortality rate was observed among those who received tocilizumab, 21 vs. 10 patients (p=0.043), RR = 2.1 (95% CI 1.0-4.3). In MAS patients, tocilizumab decreased the mortality, 13 vs. 6 patients (p=0.013), RR = 0.50 (95% CI 0.25-0.99). Сonclusions: Tocilizumab therapy in patients with COVID-19 and CRS was associated with increased mortality, while in MAS patients it contributed to reduced mortality.

With increasing fatalities, the COVID-19 pandemic constitutes a formidable global health challenge. The causative agent, SARS-CoV-2 constantly tests the efficacy of the immune system of its victims. The protective ability of the innate immune system as the first responder largely determines the progression of disease and its clinical prognosis. Evidence suggests that mortalities associated with COVID-19 are largely due to hyperinflammation and a dysregulated immune response. Consequently, the degree of the release of pro-inflammatory cytokines such as IL1, IL-6, and TNF alpha remarkably distinguishes between mild and severe cases of COVID-19. The early prediction of a cytokine storm is made possible by several serum chemistry and hematological markers. The prompt use of these markers for laboratory tests, and the aggressive prevention and management of a cytokine release syndrome is critical in determining the level of morbidity and fatality associated with COVID-19. With respect to the SARS-CoV-2 and the host cell, this literature review focuses on the dynamics of the COVID-19 disease highlighting on the pathogenesis, and the markers of Cytokine Storm. It also proffers solutions by critically looking at the current and potential pharmacological agents that are or can be used to mitigate and manage cytokine storms.

Volunteering has many social, emotional and health benefits and could be an option for people with younger/early onset dementia to engage in stage/age-appropriate, personally meaningful activity within their local community. Audio data of people with young onset dementia discussing their volunteering experiences were taken from the Dementia Diaries and co-analysed. This study explored how people with dementia volunteer in the UK, the benefits and barriers, and how we can improve access to volunteering opportunities. The findings suggest that stigma is the overarching concept (or net) which influences people’s experiences of volunteering with dementia. Within the stigma net, three themes were developed that employed a lifespan approach to challenging said stigma: 1) Valuing the past, 2) Valuing the present and 3) Valuing the future, each with additional subthemes. This research contributes to the limited pool of literature that highlights the clear benefits of volunteering for people with young onset dementia, while also considering how dementia stigma can create practical and institutional barriers to accessing volunteering. Guidance is provided for how to deliver meaningful and accessible volunteering opportunities.

Introduction: Type 1 diabetes mellitus is a chronic disease of autoimmune etiology that is highly prevalent in childhood. In the last decade, the possibility of using the Bacillus Calmette-Guérin vaccine for the treatment of this disease has been studied thanks to its immunomodulatory action . Objectives: The objective of this work is to carry out a systematic review of the available scientific evidence on the relationship between the tuberculosis vaccine and the treatment of diabetes in childhood. Secondarily, the aim is to study the incidence of Type 1 Diabetes Mellitus in a cohort of children from the Basque Country according to whether or not they have received the vaccine. Methods: An exhaustive bibliographic search has been carried out on the evidence available to date. For the epidemiological study in Euskadi, a comparison of accumulated incidences between vaccinated and unvaccinated population groups was made. Results: According to the literature analyzed, There is more and more evidence about the possible use of the tuberculosis vaccine in Type 1 Diabetes Mellitus. The results of our study were not conclusive, but we believe that it is necessary to continue with long-term studies to eliminate biases. Conclusions: The Bacillus Calmette-Guérin vaccine could be used for the treatment of autoimmune, allergic, infectious or oncological processes, although more studies are still necessary in this regard.

This is growing recognition of early onset gastrointestinal (GI) malignancies in young adults

Anderson – Fabry disease (AFD) is a rare, X-linked lysosomal storage disorder caused by a mutation in the α-Galactosidase A gene resulting in α-Galactosidase A enzyme (α-Gal A) deficiency. The metabolic defect leads to progressive accumulation of glycosphingolipids and structural and functional impairment of affected organs. Due to the inheritance pattern, male patients are hemizygous with more severe manifestations of the disease as compared to females who in most cases are heterozygous with delayed and variable clinical presentation caused by uneven X – chromosome inactivation. Fabry disease cases are often identified by targeted screening programs in high-risk groups, such as in patients with end-stage renal disease, premature stroke or unexplained cardiomyopathy. Here we describe a unique case of homozygous female patient identified by a nationwide screening program in hypertrophic cardiomyopathy patients. Before the systematic screening, the patient had a diagnosis of hypertrophic obstructive cardiomyopathy and was treated accordingly including alcohol septal ablation to reduce the obstructive gradient. The confirmation of Fabry disease has led to discovery of the same variant in several members of her family. The identified variant was c.644A>G, p.Asn215Ser (N2015S) known to cause predominant cardiac involvement with late onset of the disease. The variant is amenable for an oral therapy by the small molecular chaperone migalastat which was started, then interrupted for recurrence of patient´s migraine and then re-initiated again after two years. During this period the patient received enzyme replacement therapy by agalsidase beta but developed a progressively worsening venous access. Our case illustrates the importance of systematic screening of patients with clinical evidence of hypertrophic cardiomyopathy in whom routine diagnostic process fails to discover Fabry disease, in particular variants with late onset cardiac manifestations. Many of the late onset variants are amenable for orally active therapy by migalastat which significantly improves the comfort of the treatment. Its long term results are analysed by a large international “Follow-me” registry which was designed to verify the validity of pivotal trials with migalastat in Fabry disease.

Early onset neonatal sepsis is a significant contributor to neonatal morbidity and mortality. Although blood cultures remain the diagnostic gold standard, they detect pathogens in only a minority of suspected cases. This study compared the accuracy of blood cultures with a rapid multiplex PCR test. Newborns at risk for neonatal sepsis were prospectively screened as recommended per national guidelines. Evaluations included laboratory parameters (CrP, IL6, differential blood count), blood culture, and a molecular multiplex PCR test (ROCHE LightCycler SeptiFast) identifying 20 common microbial agents. Blood samples were taken simultaneously from umbilical cord or venous sources on the first day of life. Of 229 infants included, 69% were born preterm. Blood culture and multiplex PCR sensitivity were 7.4% and 11.1% respectively. Specificity, negative and positive predictive values between methods showed no significant variance, though multiplex PCR had more false positives due to contamination. The limited sensitivity of blood cultures for early onset neonatal sepsis is concerning. Despite quicker results, multiplex PCR does not enhance diagnostic accuracy or antibiotic therapy guidance, thus it can not be recommended for this indication.

The aim of this study was to determine the potential of early inflammatory markers to diagnose late-onset neonatal sepsis - procalcitonin (PCT), interleukin 6 (IL-6), interleukin 8 (IL-8) and endocan (ESM-1), and to compare them with routinely used markers. A prospective (January, 2022 – January, 2023) clinical-epidemiological study was conducted in a third level NICU in Pleven, Bulgaria. Patients with suspected nosocomial infection and healthy controls were tested. A sandwich ELISA method was used to measure the serum concentrations. Sixty newborns with an average gestational age of 29.75 ± 3.61 gestational weeks were included, of which 35 % were symptomatic and infected, 33.3 % were symptomatic but uninfected, and 31.7 % were asymptomatic controls. The mean values of PCT, IL-6, I:T index and PLT differ significantly in the three groups. For ESM-1, IL-8 and CRP, the difference was statistically insignificant. The best sensitivity (78%) and negative predictive value (84%) was found for IL-6. The combination of PCT + IL-6 + I:T+ PLT demonstrated high precision (78%) and best sensitivity (94%) and negative predictive value (95%). The introduction into routine practice of indicators such as PCT and IL-6 may provide an opportunity to promptly optimize the diagnostic and therapeutic approach to LOS.

In this paper, the ductile fracture mechanism is discussed. The results of the numerical and experimental analyses are used to estimate of the onset of the crack front growth . It is assumed that the ductile fracture in front of the crack starts at the location along the crack front where the accumulated effective plastic strain reaches a critical value. It is also assumed that the critical effective plastic strain depends on the stress triaxiality and the Lode angle. The experimental programme was performed using five different specimen geometries, three different materials and three different temperatures of +20°C, -20°C and -50°C. Using the experimental data and the results of the finite element computations, the critical effective plastic strains are determined for each material and each temperature. However, before the critical effective plastic strain is determined, a careful calibration of the stress–strain curves was performed after modification of the Bai–Wierzbicki procedure. Finally, by analysing the experimental results recorded during the interrupted fracture tests and scanning microscopy observations, the research hypothesis is verified.

Life on Earth evolved to accommodate the biochemical and biophysical boundary conditions of the planet millions of years ago. The former includes nutrients, water, and ability to synthesize other needed chemicals. The latter include the 1 g gravity of the planet, radiation, and the geomagnetic field (GMF)of the planet. How complex life forms have accommodated the GMF is not known in detail considering that Homo sapiens evolved a neuro system and a cardiovascular system that develops electromagnetic fields as part of their functioning. In addition, many proteins and physiologic processes utilize Fe ions, an ion that exhibits magnetic properties. Thus, complex organisms such as current humans generate magnetic fields, contain significant quantities of the Fe ion, and also respond to exogenous-supplied static and electromagnetic fields. Whether humans can store information in self-generated magnetic fields remains to be determined. Given the current body of literature, it remains somewhat unclear how Homo sapiens use exogenous magnetic fields to regulate function, and what can happen if the boundary condition of the GMF of Earth is no longer exerting an effect. Proposed deep space flights to destinations such as Mars will provide some insights as space flight could not have been anticipated by evolution. The results of such space flight “experiments” will provide new insights in the role of magnetic fields on human functioning. The outcomes may also have implications for those on Earth as magnetic field influences may play a role in developmental conditions such as autism and senescence-associated conditions such as dementia when integration of the biological and biophysical aspects of humans of humans are required for effective functioning. This review will discuss the involvement of magnetic fields on various normal and disturbed processes in humans while on Earth and then further discuss potential outcomes when the GMF is no longer available to impact host systems. Thus, the GMF of the Earth has been present throughout evolution but details of its role in human functions still remain to be elucidated.

A microfinance scheme has emerged as a crucial tool in reducing poverty gaps in many developing countries. A notable player in the arena is Amanah Ikhtiar Malaysia (AIM), a pioneer in microfinancing in Malaysia since 1987. AIM’s microfinance program injects small-scale businesses, particularly benefiting single mother entrepreneurs, contributing to capacity-building and empowerment. However, the advent of the COVID-19 pandemic, coupled with Movement Control Order (MCO), has adversely affected various business sectors and vulnerable groups, including single mothers engaged in microfinancing enterprises. This study employs primary data to assess the impact of AIM’s microfinancing programs on single-mother entrepreneurs during the crisis. Utilizing a quantitative approach with a two-stage sampling process involving 422 respondents in urban areas, the research evaluates the relationship between empowerment indicators (economic, social, digital, and psychological) and management and governance aspects of program effectiveness. The findings reveal that the microfinancing program’s overall effectiveness, economic, digital and psychological empowerment indicators, and program management are at a moderate level, while social empowerment is high. Economic and digital empowerment, along with effective management, positively and significantly influence program effectiveness, whereas social empowerment has a negative and significant impact. The study concludes with recommendations for enhancing AIM’s microfinance program, equipping single mother entrepreneurs to better navigate future challenges, and informing policy formulation related to their empowerment.

The prediction of an extremely severe cyclonic storm (ESCS) is one of the challenging issues due to increasing intensity and its life period. In this study, an ESCS Fani that developed over Bay of Bengal region during 27 April - 4May, 2019 and made landfall over Odisha coast of India is investigated to forecast the storm track, intensity and structure. Two numerical experiments (changing two air-sea flux parameterization schemes; namely FLUX-1 and FLUX-2) are conducted with the Advanced Research version of the Weather Research and Forecasting (ARW-WRF) model by using a moving nest with fine horizontal resolution about 3 km. The high resolution (25 km) NCEP operational Global Forecast System (GFS) analysis and forecast datasets are used to derive the initial and boundary conditions, the ARW model initialized at 00 UTC 29 April 2019 and forecasted for 108 hours. The forecasted track and intensity of Fani is validated with available India Meteorological Department (IMD) best-fit track datasets. Result shows that the track, landfall (position and time) and intensity in terms of minimum sea level pressure (MSLP) and maximum surface wind (MSW) of the storm is well predicted in the moving nested domain of the WRF model using FLUX-1 experiment. The track forecast errors on day-1 to day-4 are ~ 47 km, 123 km, 96 km, and 27 km in FLUX-1 and ~54 km, 142 km, 152 km and 166 km in Flux-2 respectively. The intensity is better predicted in FLUX-1 during the first 60 h followed by FLUX -2 for the remaining period. The structure in terms of relative humidity, water vapor, maximum reflectivity and temperature anomaly of the storm is also discussed and compared with available satellite and Doppler Weather Radar observations.

(1) Background: Cameron County, which is located in the Rio Grande Valley, holds historical records for storm surges with noticeable property damage, fatalities, and injuries; (2) Methods: using storm surge hazard datasets from the National Oceanic and Atlantic Agency (NOAA), and American Community Survey (ACS) 2019 datasets and Geographic Information System (GIS), the study estimates at-risk population and their socio-demographic attributes; (4) Conclusions: Estimated water levels of a storm surge could be reached up to 5 feet in category 1 event, 9 feet in category 2, 17 feet in category 3, and above 20 feet in category 4 and 5. In the category 5 event, there is an estimated 37% (159,659) of the total county’s population (434,294) will be under flooded water. Suggestions are made to better prepare and successfully evaluate.

Plant species with anti-inflammatory properties might play an essential role in combatting COVID-19 via reducing cytokine storms. We aimed to review the extant evidence of the potential therapeutic efficacy of natural products against cytokine storms by inhibiting interleukin-6 (IL-6) as a major pathological mediator. Data were collected following an electronic search in major databases (Pubmed, Scopus, Web of Science, Google Scholar) and also preprint articles on preprint and medRxiv servers by using a combination of relevant keywords. Seventeen active compounds and medicinal plants were found and reviewed in the present review. Results of both in-vivo and in-vitro experiments conducted on these compounds showed that Phillyrin, SMFM, Qiangzhi decoction, curcumin, Shen-Fu, Forsythia, and Alpha-Mangostin inhibit the production of IL-6. Andrographolide and Liu Shen Wan have an inhibitory effect on releasing this agent, while Ilex Asprella and Deoxy-11,12-didehydroandrographolide and naringin reduce the expression of IL-6. Theaflavin and Cholorogenic acid inhibit the secretion of IL-6, Xuebijing, and Chai-Hu-Gui-Zi-Gan-Jiang-Tang and Lipanpaidu prescription can reduce the serum level of IL-6. These agents also effectively improve infected lungs, increase survival rates, and minimize tissue damage. Medicinal plants and their phytochemical ingredients with down-regulatory effects on the expression of IL-6 have a potential influence on the inhibition of cytokine storms during viral infection caused by COVID-19. Therefore, phytochemicals could be regarded as promising candidates for managing cytokine storm inflammatory responses due to COVID-19 infection.

Coronavirus disease 2019 (COVID-19) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in tremendous morbidity and mortality worldwide. A major underlying cause of COVID-19 mortality is a hyperinflammatory cytokine storm in severe/critically ill patients. Although many clinical trials are testing the efficacy of targeting inflammatory cytokines/chemokines in COVID-19 patients, the critical inflammatory mediator initiating COVID-19 patient death is undefined. Here we suggest that the immunopathological pathway leading to COVID-19 mortality can be divided into three stages with distinct clinical features that can be used to guide therapeutic strategies. Our interpretation of the recently published clinical trials from COVID-19 patients suggests that the clinical efficacy in preventing COVID-19 mortality using IL-1 blockade is subjected to notable caveats, while that for IL-6 blockade is suboptimal. We discuss critical factors in determining appropriate inflammatory cytokine/chemokine targets, timing, and combination of treatments to prevent COVID-19 mortality.

Dust storms and wildfires occur frequently in southeastern Australia. Their effects on ecology, environment and population exposure have been the focus of many studies recently. Dust storms do not emit ground-sequestered carbon but wildfires emit significant quantities of carbon into the atmosphere. However, both natural events promote phytoplankton growth in water bodies because carbon, and other trace elements such as iron, deposit on the surface water of oceans. Carbon dioxide is reabsorbed by phytoplankton via photosynthesis. The carbon balance cycle due to dust storms and wildfires are not well known. Recent studies on the carbon emission of the 2019-2020 summer wildfires in eastern Australia indicated that this megafire event emitted approximately 715 million tonnes of CO2 (195 Tg C) into the atmosphere from burned forest areas. The projected increase in the frequency of wildfires due to climate change alters what was a carbon neutral process of reabsorbing emitted carbon by the forests, and subsequently cannot be achieved. With the result of net loss of sequestered carbon to the atmosphere, subsequently further promotes a warming climate. This study focusses on the association of dust storms and wildfires in southeastern Australia with phytoplankton growth in the Tasman Sea due to the February 2019 dust storm event and the 2019-2020 Black Summer wildfires. Central Australia and western New South Wales were the sources of the dust storm emission (11 to 16 February 2019) and the Black Summer wildfires occured along the coast of New South Wales and Victoria (from early November 2019 to early Januaray 2020). The results show the similarities and differences in the deposition of particulate matter, phytoplankton growth and carbon reabsorption patterns in the Tasman Sea from these events. Using WRF-Chem model, during the 5 days dust storm event in February 2019, approximately ~1230 tons of total dust were predicted to be deposited in the Tasman Sea while ~132,000 tons of PM10 were deposited in the early stage of the wildfires from 1 to 8 November 2019.

Background. This study aimed to establish a prognostic nomogram for predicting overall survival (OS) and cancer-specific survival (CSS) of patients with early-onset endometrial cancer (EOEC). Methods. Patients diagnosed with EOEC during 2004-2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression analyses were performed to ascertain the independent factors impacting the prognosis of EOEC patients, while a prognostic nomogram was established. Its performance was verified by the receiver operating characteristic (ROC) curves, and calibration plots. The prediction accuracy and clinical net benefit between the model, TNM stage and SEER stage were further compared by the concordance index (C-index) and decision curve analysis (DCA). Results. A total of 4415 eligible patients with EOEC were identified and enrolled in this study. Independent prognostic factors for OS and CSS were confirmed by multivariate Cox regression, which were further incorporated to constructed a nomogram. ROC curves and calibration curves indicated an optimal accuracy of the nomogram. Meanwhile, the C-index and DCA showed the predictive capability and the clinical applicability of the nomogram was superior over the TNM stage and SEER stage. Conclusions. Nomogram based on risk factors was developed as an individualized tool to predict OS and CSS for EOEC patients. The novel tool will assist in patient counseling and selection of appropriate therapeutic regimens.

Over the last decade, advances in our understanding about the genetic architecture of complex traits and common diseases, have increased our ability to perform susceptibility genetic testing for diseases in asymptomatic individuals. These technological developments raise complex ethical, legal and social considerations. Here we discuss a series of ethical issues associated with susceptibility genetic testing for Alzheimer's and Parkinson's disease. These include, amongst others, informed consent, disclosure of results and unexpected findings, mandatory screening, privacy and confidentiality, and stigma and genetic discrimination. As knowledge of the genetic basis of these diseases continues growing, and as genetic testing becomes more widespread, we anticipate that it will become increasingly important for scientists and clinicians to engage in the conversation about the ethical, social and policy implications of these technologies.

Severe thunderstorms are often accompanied by strong vertical air currents, temporary wind gusts, and heavy rainfall. The development of this atmospheric phenomenon over tropical shallow water zones, such as bays, can lead to intensification of atmospheric disturbances and produce a small-scale storm surge. Here, the storm surge that occurred on 19 March 2017 in the Persian Gulf coastal area has been investigated. Air temperature, precipitation, mean sea level pressure, wave height, wind direction, wind speed, geopotential height, zonal components, meridional winds, vertical velocity, relative humidity, and specific humidity obtained from the European Centre for Medium-Range Weather Forecasts (ECMWF (and Global Forecast System (FNL) were used to implement the Weather Research and Forecasting (WRF) model. The results showed that the main cause of the storm surge was the occurrence of a supercell thunderstorm over the Persian Gulf. The formation of this destructive phenomenon resulted from a downburst under Cumulonimbus cloud and high-velocity air subsidence, after collision with the sea surface coinciding with the high tide. This caused a severe, yet temporary, gust, which in turn caused the creation of the four waves of 3.1 m height along the coast of Bandar Dayyer.

In dermatological practice, disturbances of the skin microbiome are found in various infectious and inflammatory dermatoses featuring one or more skin lesions with loss of tissue, directly exposing skin layers to microbial invasions. Literature data on the incidence of cutaneous-onset sepsis are, however, scarce. This retrospective observational study assessed hospital admissions for primary skin lesions with vs. without bacterial infections and sepsis during 2020-2022 in the largest emergency hospital in NE Romania. Of 509 patients 441 had infected lesions, 78 had sepsis caused by venous ulcers microbial eczema cellulitis, superinfected bullous dermatoses, erysipelas, erythroderma. Cultured samples revealed S. aureus, P. aeruginosa, E. coli, with K. pneumoniae, S. β-hemolytic associated with sepsis even if rarer. Clinical manifestations included ulcerations, erosions, fissures, excoriations, bullae, vesicles, pruritus, tumefaction, edema, fever, chills, pain, adenopathy, mildly altered mental status. Underlying chronic heart failure, atrial fibrillation, anemia, type-1 diabetes mellitus were comorbidities associated with infection and sepsis. Significant associations and risk factors, including their combined effects, are discussed to draw attention to the need for further research and adequate management to prevent sepsis in adult patients of any age presenting with infected skin lesions (especially cellulitis) and comorbidities (especially type 1 diabetes mellitus and anemia).

Background: Intradialytic hypotension (IDH) is a critical pathological condition associated with all−cause mortality in patients undergoing hemodialysis (HD). However, few studies have investigated IDH-related changes in hepatic and cerebral regional tissue oxygen saturation (rSO2). This study investigated IDH-induced changes in hepatic and cerebral rSO2. Methods: Hepatic and cerebral rSO2 during HD were measured using an INVOS 5100C oxygen saturation monitor, and their percentage (%) changes during IDH development were analyzed. Ninety-one patients undergoing HD were investigated, including 20 with IDH development. Results: In patients with IDH, % changes in hepatic and cerebral rSO2 decreased at IDH onset. Additionally, the % change in hepatic rSO2 was significantly larger than those in cerebral rSO2 (P < 0.001). In patients without IDH, no significant differences were found between the % changes in hepatic and cerebral rSO2 at time of the lowest systolic blood pressure during HD. Multivariable linear regression analysis showed that the difference between the % change in cerebral and hepatic rSO2 was significantly associated with IDH development (P < 0.001) and ultrafiltration rate (P = 0.010). Conclusion: Hepatic and cerebral rSO2 significantly decreased in IDH development and hepatic rSO2 was more largely decreased than cerebral rSO2 at IDH onset.

Introduction: Unlike cigarette smoking, secondhand smoke (SHS) has not been as well described as an environmental risk for Multiple sclerosis (MS) nor as a risk factor for disease progression. We systematically reviewed the association between SHS and the risk of onset and/or progression of MS.Methods: We systematically screened MEDLINE/PUBMED, Science Direct, LILACs, and SCIELO searching for publications between January 1st , 2010, and July 5, 2021 with the following keywords: “multiple sclerosis and smoking”; “multiple sclerosis and passive smoking”; “multiple sclerosis and secondhand smoking”. An 11-year filter was applied from 2010 to 2021. Results: Fifteen articles were included in this review, which consisted of systematic reviews with meta-analysis (N = 2), systematic reviews (N = 2), and observational studies (N = 11). Both meta-analyses reported an impact of SHS on MS onset among secondhand smokers. One of the systematic reviews selected two observational studies showing the association between SHS and MS development, and one study that did not find a significant association between SHS and the risk of MS development. The other systematic review identified selected eight articles showing a relationship between SHS and MS. Seven observational studies reported higher odds of MS onset when associated with SHS. Four observational studies did not show a relationship between SHS and MS onset or progression.Discussion: Most articles showed a positive association between SHS exposure and the risk of developing MS. On the other hand, an association between SHS and a higher risk for MS progression could not be established.

We present a case of adult-onset systemic chronic active EBV disease (CAEBV) in a 40-year-old woman with chronic HBV hepatitis. Initial symptoms resembled a viral illness, progressing to recurrent fever, transaminitis, and anasarca. Investigations revealed high-level EBV viremia and an abnormal T-cell population in liver and bone marrow, indicative of CAEBV. Liver biopsy showed CD3+ T-cells lacking TCRbeta and displaying dim/negative CD5, with elevated EBV-infected T-cells. Next-generation sequencing identified rare variants in CREBBP, SPEN, TP73, and PLCG2, suggesting potential contributions to disease pathogenesis. This case underscores diagnostic challenges and management complexities of adult-onset CAEBV, particularly with underlying chronic HBV infection. Genomic profiling offers crucial insights into the molecular landscape of rare lymphoid malignancies, highlighting the importance of personalized treatment strategies. The distinct immunophenotypic features underscore the heterogeneity in EBV-associated T-cell LPDs, urging further research for optimized clinical management

Background: The SARS-CoV-2 virus is a new highly pathogen virus that can suppress cell immune response (Poly ADPR process, and interferon releasing in infected cell) by viral macrodomain and create fatal pneumonia. Cytokine storm phenomenon which can create consequence of SARS COV-2 by increase of the performance of human TRPM2, is a dangerous condition for human and its body organ such as kidney, heart, and liver. it seems like prevention of beginning of these events is necessary. Material and methods: in this study drug and drug like database was used for inhibition of the viral macrodomain and human TRPM2 that can initiate of the viral cell cycle infection and human cytokine storm respectively. Ligand base drug designed, pharmacophore modeling, docking and molecular dynamic simulation was performed Results: among up to billion compounds, 20 compounds were screened by infinisee program. Then 7 compounds were selected by pharmacophore modeling. between 7 compounds, 5 compound was removed because of high similarity to ADPR and possibility of toxic effect for human RNA and DNA polymerase. One compound was losartan and selected for docking and molecular dynamic simulation. Conclusion: losartan earned a proper dock score and binding affinity to create the complexes with TRPM2 and macrodomain. Molecular dynamic simulation has shown losartan had an adequate binding free energy for human trpm2 and viral macrodomain. The inhibitory effect of losartan on these protein has shown and it could interfere in several points (PARP, PARG- macrodomain and TRPM2) and decreases oxidative stress, apoptosis, cytokine storm in COVID-19.

Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder. Diagnosis can take a long time, especially in the presence of confounding factors, and it is, at least in part, of exclusion. AOSD is generally mild, however a small percentage of patients can develop a fearsome as well potentially fatal complication, the macrophage activation syndrome (MAS), which is also referred to as hemophagocytic lymphohistocytosis (HLH). This condition is correlated with a cytokine storm production and monocyte/macrophage overactivation, and typically occurs with rash, pyrexia, pancytopenia, hepatosplenomegaly and systemic involvement. Exitus occurs in approximately 10% of cases. The Histiocyte Society, which is a nonprofit organization committed to improving the lives of patients with histiocytic disorders, currently suggests etoposide in combination with dexamethasone for the treatment of HLH/MAS, although a multidisciplinary collaboration using the resources and expertise of several specialists (e.g. rheumatologist, infectiologist, critical care medicine specialist) is always recommended. Hereby we propose the detailed description of the clinical case of a previously healthy young woman in which MAS was the dramatic onset manifestation of AOSD and whose diagnosis posed a real clinical challenge.

Cardiac fibrosis is a severe outcome of Chagas disease (CD), caused by the protozoan Trypanosoma cruzi. Clinical evidence revealed a correlation between fibrosis levels with impaired cardiac performance in CD patients. Therefore, we sought to analyze the effect of inhibitors of TGF- (pirfenidone), p38-MAPK (losmapimod) and c-Jun (SP600125) on the modulation of collagen deposition in cardiac fibroblasts (CF) and in vivo models of T. cruzi chronic infection. Sirius Red/Fast green dye was used to quantify both collagen expression and total protein amount, assessing cytotoxicity. The compounds were also used to treat C57/Bl6 mice chronically infected with T. cruzi, Brazil strain. We identified an anti-fibrotic effect in vitro for pirfenidone (TGF-β inhibitor, IC50 114.3 μM), losmapimod (p38 inhibitor, IC50 17.6 μM) and SP600125 (c-Jun inhibitor, IC50 3.9 μM). This effect is independent of CF proliferation since these compounds do not affect T. cruzi-induced host cell multiplication as measured by BrdU incorporation. Assays of chronic infection of mice with T. cruzi have shown a reduction in heart collagen by pirfenidone. These results propose a novel approach to fibrosis therapy in CD, with the prospect of repurposing pirfenidone to prevent the onset of ECM accumulation in the heart of the patients.

Irrigation is a useful crop enhancement procedure up to the point where free surface water appears. Thereafter, water can begin to flow into waterways, leaching nutrients and giving rise to environmental damage, as well as being a waste of a precious resource. The current work addresses the problem of measuring free water on the surface of agricultural soils by a real-time acoustic remote sensing method. Directional acoustic transmitter and receiver arrays are used to define a ‘footprint’ on the ground from which changes in reflectance are sensed. These arrays are mounted on a moving irrigator. Chirp signals are used to provide along-path resolution and to ensure robustness against unwanted acoustic background noise from farm machinery and the irrigator. Field measurements have been conducted above a well-defined ‘quadrat’ with controlled and measured water content, and also with the instrument mounted on an operational irrigator. A structured light camera mounted above the footprint is used to validate surface water fraction. It is found that the areal fraction of free water on the soil surface can be reliably estimated from changes in the amplitude of the reflected sound waves. The mechanism giving rise to the observed acoustic reflectivity changes is discussed and a model is developed which agrees with normalized intensity observations with a coefficient of determination R2 between 0.65 and 0.83. The rms error between model predictions and observations is comparable to the rms variation of the measurements, indicating that there is insignificant error due to the choice of model.

Acute kidney infection (AKI) occurred by tubular necrosis and glomerular dysfunction caused by many factors. SARS CoV-2 infection identified to cause fatal AKI. This paper aims to review the effect of covid-19 infection on the failure of the kidney and its mechanism. It identified that the SARS-CoV-2 received by the targeted cell by Angiotensin-converting enzyme 2 (ACE2). After the virus received by the target cells, it induces the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF), interleukin (IL)-1, and interferons (IFN) by immune cells and causes cytokine storm. The pro-inflammatory cytokines are again responsible to induce the secretion of cyclooxygenase‑2 (COX‑2), which causes inflammation and pain as well it stimulates the iNOS enzyme to produce NO which allows the vasodilation of renal arteries. The increased production of NO by iNO enhanced the vasodilation of arteries, and allows the adhesion of neutrophils to the artery, and causes damage to glomerulus and tubules. Hence, the most likely sustainable intervention could be the application of angiotensin-converting enzyme 2 (ACE2) inhibition by the receptors of the target cells in these vital organs to reduce sever destruction during treatment at the early stage of infection.

In this study, we aimed to reveal the proinflammatory effects of serum 25-hydroxyvitamin D3 (Vit D) deficiency and insufficiency in new-onset type 2 diabetes mellitus (T2DM) and prediabe-tes. We recruited 84 prediabetes patients, 94 new-onset T2DM patients and 113 healthy partici-pants. Levels of C-reactive protein (CRP), fibrinogen, ferritin, interleukin-1β (IL-1β), interleu-kin-6 (IL-6), interleukin-8 (IL-8), tumour necrosis factor-α (TNF-α), nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) were measured in the serum of the par-ticipants. The ANOVA Bonferonni and Kruskal Wallis Dunn tests were used for the comparison of the inflammation markers and vitamin D levels between the groups. Upon covariance analy-sis with age, gender and BMI; Vit D levels of T2DM group were found to be significantly lower (p<0.003). Proinflammatory markers and CRP were found to be significantly higher in predia-betic and diabetic subjects. In the prediabetes group, IL-1β, IL-6, IL-8, TNF-α and MAPK were significantly higher in those with Vit D insufficiency and deficiency groups. In T2DM group, IL-1β, IL-6, IL-8, TNF-α, NF-κB, MAPK and CRP were significantly higher in those with Vit D insufficiency and deficiency. Our study emphasizes the proinflammatory effects of Vit D on the initiation of inflammation in both prediabetes and diabetes mellitus.

Late onset Pompe disease is a recessive lysosomal storage disease. Clinical features include skeletal muscles deficiency and diaphragm weakness. Clinical management relies on supportive treatment and mechanical ventilation in patents with chronic respiratory failure. M mode ultrasound and tissue Doppler imaging can be used to assess and to follow up diaphragm function.

Cannabinoids, mainly cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), are the most studied group of compounds obtained from Cannabis sativa because of their several pharmaceutical properties. Current evidence suggests a crucial role of cannabinoids as potent anti-inflammatory agents for the treatment of chronic inflammatory diseases; however, the mechanisms remain largely unclear. Cytokine storm, a dysregulated severe inflammatory response by our immune system, is involved in the pathogenesis of numerous chronic inflammatory disorders, including coronavirus disease 2019 (COVID-19), which results in the accumulation of pro-inflammatory cytokines. Therefore, we hypothesized that CBD and THC reduce the levels of pro-inflammatory cytokines by inhibiting key inflammatory signalling pathways. The nucleotide-binding and oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome signalling has been implicated in a variety of chronic inflammatory diseases, which results in the release of pyroptotic cytokines, interleukin-1β (IL-1β) and IL-18. Likewise, the activation of the signal transducer and activator of transcription-3 (STAT3) causes increased expression of pro-inflammatory cytokines. We studied the effects of CBD and THC on lipopolysaccharide (LPS)-induced inflammatory response in human THP-1 macrophages and primary human bronchial epithelial cells (HBECs). Our results revealed that CBD and, for the first time, THC, significantly inhibited NLRP3 inflammasome activation following LPS + ATP stimulation, leading to a reduction in the levels of IL-1β in THP-1 macrophages and HBECs. CBD attenuated the phosphorylation of nuclear factor-κB (NF-κB) and both cannabinoids inhibited the generation of oxidative stress post-LPS. Our multiplex ELISA data revealed that CBD and THC significantly diminished the levels of IL-6, IL-8, and tumor necrosis factor-α (TNF-α) after LPS treatment in THP-1 macrophages and HBECs. In addition, the phosphorylation of STAT3 was significantly downregulated by CBD and THC in THP-1 macrophages and HBECs, which was in turn, attributed to the reduced phosphorylation of tyrosine kinase-2 (TYK2) by CBD and THC after LPS stimulation in these cells. Overall, CBD and THC were found to be effective in alleviating the LPS-induced cytokine storm in human macrophages and primary HBECs, at least via modulation of NLRP3 inflammasome and STAT3 signalling pathways. The encouraging results from this study warrant further investigation of these cannabinoids in vivo.

Background: The association of age at onset of CRC and prevalence of KRAS G12C mutation is unclear; Methods: Retrospective multicenter study evaluating metastatic CRC patients from January 2019 to July 2023 treated at Oncoclinicas units, tested for tissue-based KRAS/NRAS and BRAF mutations in a centralized genomics lab. Mismatch repair (MMR) status was retrieved from different labs and electronic medical records, as were patient demographics (age, gender) and tumor sidedness. Chi-square test was used to examine the association between clinical and molecular variables, with p value <0.05 being statistically significant; Results: A total of 858 cases were included. The median age was 63.7 years (range 22-95) and 17.4% were less than 50 years old at diagnosis of metastatic CRC. Male patients represented 50.3% of the population. Sidedness distribution was left-side 59.2%, right-side 36.8% and not specified 4%. Prevalence of KRAS mutation was 49.4% and NRAS mutation 3.9%. Among KRAS mutated tumors, the most common variants were G12V (27.6%) and G12D (23.5%), while KRAS G12C was less frequent (6.4%), which represented 3.1% of the overall population. BRAF mutant cases were 7.3%, most commonly V600E. Only 5 (<1%) non-V600E mutations were detected. MSI-high or dMMR was present in 14 cases (1.6%). In the age-stratified analysis, left-sidedness (p<0.001) and KRAS G12C mutation (p=0.046) were associated with younger age (<50 years). In the sidedness-stratified analysis, BRAF mutation (p=0.001) and MSI-high/dMMR status (p=0.009), were more common in right-sided tumors; Conclusions: Our data suggest that KRAS G12C mutations are more frequent in early-onset metastatic CRC. To the best of our knowledge, this is the largest cohort in the Latin American population with mCRC reporting RAS, BRAF and MSI/dMMR status.

Background: The potential impact of the pandemic on mental health should not be overlooked, especially among vulnerable populations such as women who gave birth during the COVID-19 pandemic. The aim of the study was to assess the mental health status of women who gave birth during a pandemic and to examine the possible links between the onset of depressive disorder symptoms in close proximity to the time of delivery and the socio-demographic conditions, health status and obstetric circumstances of the patients. Materials and Methods: The study is a cross-sectional survey conducted from 01.03.2020 to 01.03.2023, during the period of SARS-CoV-2 (COVID-19) pandemic, based on a retrospective evaluation of 860 postpartum women. The screening tool used to assess symptoms of postpartum depression was the Edinburgh Postnatal Depression Rating Scale (EPDS) questionnaire. The questionnaire was completed both in the Obstetrics and Gynaecology Clinical Sections I and II of the "Pius Brînzeu" County Emergency Hospital from Timisoara, Romania and online using Google Forms. Results: The highest severity of postpartum depression symptoms was observed during the COVID-19 pandemic. The results of the study conducted during the period of SARS-CoV-2 pandemic (COVID-19) showed that the prevalence of major postpartum depressive disorder (EPDS ≥ 13) was 54.2% (466 patients), while 15.6% (134) had minor depressive disorder (10 &lt; EPDS ≤ 12) in the first year after delivery. Comparing these results with those obtained in research conducted before the onset of the pandemic period shows an alarming increase in the prevalence of postpartum depression. Risk factors associated with postpartum depression included type of delivery, level of education, socio-economic conditions, health status, age, background, personal obstetric history (number of abortions on demand, parity). Conclusions: The effects of the pandemic on mental health are of particular concern for women in the first year after childbirth. Observing these challenges and developing effective measures to prepare our health system early can help and facilitate effective mental health screening for postpartum women, promoting maternal and child health.

Owing to its unique position within multiple monsoon regimes, latitudinal extent, and complex topography, Vietnam is divided into seven agroclimatic zones, each with distinct rainy season characteristics. Variation in the dominant rainfall system across zones affects the rainfall climatology, the primary water resource for regional crops. This study explores the creation of an agronomic rainy season onset based on high-resolution rainfall data for each agroclimatic zone for applications in an agricultural context. Onset information has huge practical importance for both agriculture and the economy. The spatiotemporal characteristics of zonal onset date are analyzed using integrated approaches of spatial and interannual variability, temporal changes, and estimation of predictability using teleconnection with Niño 3.4 sea surface temperature anomalies (SSTA) for 1980 to 2010. Results suggest that northern and southern zones experience regional onset dates in May, while the central zones experience rainy season onset in late August. The regional variability of rainy season onset is lower in a single dominant monsoon regime (northern and southern zones) and higher in latitudinally extended zones on the border of monsoon regimes (central zones). The interannual variation in rainy season onset date is found to be approximately 2 weeks across all agroclimatic zones. The significant negative trend in rainy season onset date is found for Central Coast and South Central Coast zones, suggesting that the onset date shifted earlier for the entire period. In the decadal scale, the zonal mean onset date shifted later in the Northwest and earlier in the Central Highlands. Out of the seven climate zones, a significant positive correlation is only noticed in the Central Highlands and South zones between zonal mean onset date and Niño 3.4 SSTA for Dec-Jan-Feb, suggesting the potential of seasonal scale predictability of rainy season onset date with respect to preceding El Niño-Southern Oscillation (ENSO) events.

The ongoing COVID-19 pandemic is one of the biggest health and societal challenges of the recent decades. Among the causes of mortality triggered by SARS-CoV-2 infection, the presence of an inflammatory "cytokine storm" (CS) at later stages of the disease has been found to play a determinant role. Here, we used available transcriptomic data from the bronchoalveolar lavage fluid (BALF) of COVID-19 patients suffering from a CS to obtain gene-signatures associated to this pathological process. Using these signatures, we interrogated the Connectivity MAP (CMap) dataset that contains the effects of over 5,000 small molecules on the transcriptome of human cancer cell lines, and looked for molecules which effects on transcription mimic or oppose those associated to the CS. Consistent with their medical use, this analysis found a significant enrichment of glucocorticoids or inhibitors of the Janus Kinases (JAK) as drugs that could revert the CS. On the other hand, molecules that potentiate the immune response such as PKC activators are predicted to worsen the CS. Besides these expected findings, our analysis also reveals a potential effect of the antibiotic doxycycline or MAPK/RAF/MEK inhibitors in reverting the CS, or of topoisomerase inhibitors and the anti-alcohol abuse drug disulfiram in potentiating its effects. Finally, our analyses support that the gender-related differences in the severity of COVID-19 are related to the anti-inflammatory properties of female hormones. While acknowledging that this is an analysis based on limited available data, we decided to share it as a resource that might help others in the selection of drugs that could be tested in the context of experimental models of CS triggered by viral infections.

Objectives: In December 2019 a novel human-infecting coronavirus, SARS-CoV-2, has emerged. The WHO has stated the epidemic as a “public health emergency of international concern”. A dramatic situation has emerged with thousands of deaths, occurring mainly in the aged and very ill people. Epidemiological studies suggest that immune system function is impaired in elderly individuals and these subjects often present a severe deficiency in nutrients as fatsoluble and hydrosoluble vitamins. Design: In this second part of the review about Cov2 in aged people, we searched for studies describing the possible efficacy of vitamins A, D, E and C in improving the immune system function and their possible activities against viruses. Results: Vitamins may shift the proinflammatory Th17 mediated immune-response arising in the autoimmune diseases towards a T-cell regulatory phenotype. These diseases may serve as a paradigm for the study of CRS emerging in the course of SARS CoV-2 infection. Conclusion: This review discusses about the possible activity of Vitamin A, D, E and C in restoring normal antiviral Immune System function or the potential therapeutic role of these micronutrients as a part of a multi-treatment strategy against SARS-CoV-2 infection.

Diagnosis of neonatal sepsis is difficult as signs and symptoms are nonspecific. Interleukin-6 (IL-6) is a promising marker for neonatal sepsis. We aimed to test the accuracy of IL-6 in term and preterm infants after 72 hours of life (late-onset sepsis-LOS). We searched for IL-6 diagnostic accuracy studies between 1990 and 2020 using the PubMed database. Study selection was performed. The range of reported IL-6 sensitivities and specificities was 68% to 100% and 28% to 100%, respectively, the median values were 85.7% and 82% from 15 studies including 1306 infants. Subgroup analysis was performed. Sensitivity (87% vs 82%), but not specificity (both 86%), was better in preterm infants than in preterm and term infants. Early sample collection had the highest sensitivity (84%), but the lowest specificity (86%). To assess quality we used a STARD checklist adapted for septic neonates. Limitation of this review include the heterogeneous group of studies on the one side and the small number of studies on the other side that analyzed different combinations of biomarker. We concluded that IL-6 had a good performance especially in the preterm infant population and best results are achieved by measurements at the time of LOS suspicion.

Background: Over the past years, there has been a rise in the incidence of type 1 diabetes, partic-ularly among younger individuals. This concerning trend has prompted investigations into po-tential contributing factors, with intestinal dysbiosis emerging as a likely culprit for the escalating annual rates of the disease; (2) Methods: We conducted a retrospective ecologic correlational study involving 37 children from the southern region of Romania between 2019-2021. All participants were within the first six months following the onset of the disease; (3) Results: In the microbiota of the patients we observed a dysbiosis marked by an overabundance of bacteria (Clostridium coccoides, Faecalibacterium, Bacterioides, Enterobacteriaceae) and fungi, compared to the healthy control group. The Spearman correlation revealed a positive association between the presence of Bacteroides (p=0.0442), Butyricicoccus (p=0.0164), and Clostridium leptum (p=0.0023) with recent diabetes onset. Furthermore, a significant correlation was observed between younger age at onset and the pres-ence of Butyricicoccus (p=0.019). The use of antibiotics in the month preceding admission was linked to the presence of fungi in the microbiota (Candida, p=0.0442); (4) Conclusions: The dysbiosis of Romanian type 1 diabetes children correlates with inflammation, more severe onset of the disease and other au-toimmune diseases.

This study investigates the spatio-temporal variability of the onset, offset, and Length of the rainy season in Senegal over the 1981-2018 period. The onset, offset dates, and length of the rainy season are crucial parameters for agricultural planning in West Africa, which exhibits high interannual and spatial variability in rainfall. The objective is to detect and spatially classify these phenological parameters across Senegal using different approaches. Daily precipitation data from the Climate Hazards group InfraRed Precipitation with Stations (CHIRPS) dataset over the study period and ERA5 reanalysis were used. The method of was applied to detect the onset, offset dates, and length of the rainy season. The Kohonen algorithm was then used to spatially classify these parameters on topological maps. A hierarchical ascendant classification was also performed to reduce the number of classes obtained. Finally, a composite analysis of moisture transport before the onset and end of the 1984 and 2007 seasons was conducted with ERA5 data. The results show a meridional gradient of the start of the season, progressively later from southeast to northwest, while the end follows a north-south gradient. The duration of the rainy season ranges from 45 days in northern Senegal to 150 days in the south. The maximum number of dry days also decreases from north to south. The Kohonen self-organizing maps allow spatial prediction of the onset, end date, and duration of the rainy season across Senegal. The dynamics analysis reveals that early onset years are associated with stronger and earlier northward moisture transport over West Africa, underscoring the role of this parameter in triggering the rainy season. These promising results can provide an early warning to policymakers and farmers on the start and end dates of the season in each area of Senegal.

Observational studies have linked vitamin D insufficiency to pediatric type 2 diabetes (T2D) , but evidence from vitamin D supplementation trials is sparse. Given the rising prevalence of pediatric T2D in all ethnicities, determining a protective role of vitamin D has significant public health importance. We tested whether serum 25-hydroxyvitamin D (25OHD) levels are causally linked to youth-onset T2D risk using Mendelian randomization (MR). We selected 54 single nucleotide polymorphisms (SNPs) associated with 25OHD in a European genome-wide association study (GWAS) on 443,734 individuals and obtained their effects on pediatric T2D from the multi-ethnic PRODIGY GWAS (3,006 cases/6,061 controls). We applied inverse variance weighted (IVW) MR, and a series of MR methods to control for pleiotropy. We undertook sensitivity analyses in ethnic sub-cohorts of PRODIGY, and using SNPs in core vitamin D genes or ancestry-informed 25OHD SNPs. Multivariable MR accounted for mediating effects of body mass index. We found that a standard deviation increase in 25OHD in the logarithmic scale did not affect youth-onset T2D risk (IVW MR odds ratio (OR) = 1.04, 95% CI=0.96-1.13, P=0.35) in the multi-ethnic analysis, and sensitivity, ancestry-specific and multivariable MR analyses showed consistent results. Our study had limited power to detect small/moderate effects of 25OHD (OR of pediatric T2D < 1.39 to 2.1). In conclusion, 25OHD levels are unlikely to have large effects on risk of youth-onset T2D across different ethnicities.

Studies have shown that COVID-19 patients with prediabetes frequently present with high plasma glucose levels on hospital admission. However, whether the glycemic abnormalities are temporary or persist after recovery from the illness is unclear. We conducted a prospective cohort study of 69 COVID-19 patients with prediabetes (HbA1c 5.7-6.4%) who were admitted to a tertiary care hospital in Chennai, India, from May to October 2020 and were discharged alive. Over a mean follow-up of 146.6 (SD: 72.5) days, the mean fasting plasma glucose rose by 16.8 mg/dl (from 119.3-136.1 mg/dl), 2-hr post-prandial glucose by 61.0 mg/dl (from 176.2-237.2 mg/dl), and HbA1c by 0.6% (5.9-6.5%). Of the 49 (84.5%) patients who were discharged with glucose-lowering medications, 40 (81.6%) continued taking them at the first follow-up visit (mean of 50.1 days from admission), and 39 (79.6%) continued taking them at the second follow-up visit (mean of 114.3 days from first the follow-up visit). In addition, 12.1% of patients developed new-onset diabetes after recovery from the illness. Continuous monitoring of glycemia and detecting new-onset diabetes in COVID-19 patients with prediabetes after recovery are essential, as the metabolic effects of SARS-CoV-2 persist for several months.

Early detection, isolation, and management of COVID-19 patients are crucial to contain the current pandemic. The CDC in USA recently included "sudden loss of taste (dysgeusia/ageusia) and smell (anosmia/hyposmia)” as symptoms of COVID-19. If these symptoms are reliable forerunner symptoms of COVID-19, then it may facilitate early detection and containment of the disease. Hence, we systematically evaluated the contemporary evidence on dysgeusia and anosmia as trigger symptoms in COVID-19. Ovid MEDLINE, EBSCO host, and Web of Science databases were searched between December 25, 2019-May 30, 2020.Of the 13 identified records, eight (totaling 11,054 COVID-19 patients), were included, as per the selection criteria. The studies emanated mostly from the European community, as well as China, the USA, and Iran. In total, anosmia and dysgeusia symptoms were present in 74.9 % and 81.3% ambulatory as well as hospitalized, mild-to-severe cases of COVID-19 patients, respectively. The European, US, and Iran data indicate that olfactory, and gustatory symptoms appear prior to general COVID-19 symptoms in a majority of the patients. To our knowledge, this is the first systematic review analyzing the prevalence of chemosensory dysfunction in COVID-19. Further, studies are essential to evaluate their utility as harbingers of COVID-19 onset, and to establish clinical practice guidelines.

The ongoing growth of international occurrence of depression and its ability to co-occur with other serious medical disorders such as heart disease, cancer, diabetes, and Parkinson’s disease is a current public health problem. Inhibitor of DNA-Binding/Differentiation (ID) proteins are part of a group of transcriptional factors that have been seen to be involved in neurocognitive disorders and therefore, may have influence on depressive disorders. Previously, it has been established that environmental estrogenic endocrine disruptors (EEDs) such as polychlorinated biphenyls (PCBs) & bisphenol A (BPA) have played an important role in the impact of depressive disorders. Hence, based on many studies, we consider the impact of these environmental pollutants on the group of ID proteins. Improved understanding of how the interaction of ID proteins by EED exposure can influence depressive disorders will contribute essential evidence that can further benefit our public health community with innovative knowledge to prevent these types of mental illnesses.

This paper describes the dielectric relaxation spectroscopy (DRS) method for obtaining glass transition temperature and the onset of crystallinity of skim milk powder (SMP). The methodology consists of exposing SMP samples to numerous constant temperatures, T, and water activities, a_w, and measuring the relaxation time. Measurements are based on changes in the loss-tangent height at its peak frequency. Glass transition times are identified at peaks in the loss-tangent height versus time curve and the onset of crystallinity times are identified when the loss-tangent height collapses. The analysis leads to two boundary curves: glass transition T_g, a_w curve and the onset of crystallinity T_c, a_w curve. They separate the SMP stable (long shelf life) and unstable (short shelf life) regions. Two curve fitting algorithms were developed for (a) a_w², t_g curve where t_g is the time to glass transition and a_w², t_c curve where time t_c is the time to onset of crystallinity and (b) T_g, a_w and T_c, a_w boundary curves. Finally, the DRS data are compared to differential scanning calorimetry (DSC) results.

Portugal Mainland has hundreds of thousands of people living in the Atlantic coastal zone, with numerous high economic value activities and a high number of infrastructures that must be protected from natural coastal hazard, namely extreme storms and sea level rise (SLR). In the context of climate change adaptation strategies, a reliable and accurate assessment of the physical vulnerability to SLR is crucial. This study is a contribution to the implementation of flooding standards imposed by the European Directive 2007/60/EC, which requires each member state to assess the risk associated to SLR and floods caused by extreme events. Therefore, coastal hazard in the Continental Atlantic coast of Portugal Mainland was evaluated for 2025, 2050 and 2100 in the whole coastal extension with different sea level scenarios for different extreme event return periods and due to SLR. A coastal flooding probabilistic map was produced based on the developed methodology using Geographic Information Systems (GIS) technology. The Extreme Flood Hazard Index (EFHI) was determined on flood probabilistic bases through five probability intervals of 20% of amplitude. For a given SLR scenario, the EFHI is expressed, on the probabilistic flooding maps for an extreme tidal maximum level, by five hazard classes ranging from 1 (Very Low) to 5 (Extreme).

Between 11 to 15 February 2019, a dust storm originating from Central Australia with persistent westerly and south westerly winds caused high particles concentration at many sites in the state of New South Wales (NSW), both inland and along the coast. The dust continued on to New Zealand and to Antarctica in the south east. This study uses observed data from air quality monitoring stations in NSW and New Zealand, MODIS 3km AOD (Aerosol Optical Depth) product from Terra/Aqua and lidar aerosol profile from CALIPSO (Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations) satellite data, and the Weather Research Forecast WRF-Chem model based on GOCART-AFWA (Goddard Chemistry Aerosol Radiation and Transport – Air Force and Weather Agency) dust scheme and GOCART aerosol and gas-phase MOZART (Model for Ozone And Related chemical Tracers) chemistry model to study the long-range transport of aerosols for the period 11 to 15 February 2019 across eastern Australia and onto New Zealand and Antarctica. Wild fires also happened in northern NSW at the same time and their emissions are taken into account in WRF-Chem model by using Fire Inventory from NCAR (FINN) as emission input. Modelling results by the WRF-Chem model show that for the Canterbury region of South Island of New Zealand, peak concentration of PM10 (and PM2.5) as measured on 14 February 2019 at 05:00 UTC at the monitoring stations of Geraldine, Ashburton, Timaru and Woolston (Christchurch), which are more than 100km from each other and at Rangiora, Kaiapoi about 2 hours later, correspond to the prediction of high PM10 due to intrusion of dust to ground level from transported dust layer above. The Aerosol Optical Depth (AOD) observation data from MODIS Terra/Aqua and CALIOP lidar measurements on board CALIPSO satellite also indicate that high altitude of dust, originated from this dust storm event in Australia, was located above Antarctica. This study suggests that at present dust storms in Australia can transport dust from sources in Central Australia to the Tasman sea, New Zealand and Antarctica. This process has been going on for at least the last 170k years as indicated by dust found in ice cores from Antarctica and sediment records in the Tasman Sea.

Background: This paper investigates the statistical relationship between bilingualism and the Onset Age (OA) of AD and MCI across a clinical sample, consisting of 580 Alzheimer's Disease (AD) subjects and 1264 Mild Cognitive Impairment (MCI) subjects, via a statistical analysis conducted on the sample retrieved from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. Method: To investigate whether bilingualism has any correlation with the OAs of AD or MCI subjects, our study leverages the full potential of the ADNI dataset, a dataset that covers both the OA and the bilingualism status of both the AD and MCI subjects. Prior to performing any meaningful statistical analysis, a regression model and a probabilistic model were developed in parallel to fill in the missing OA and bilingualism values. A simple least-square regression model that consists of an independent variable of registered age for Mini-Mental State Examination (MMSE) score was used to estimate the OA of the AD and MCI subjects in the ADNI dataset. After filling in the missing OA values, the number of subjects relevant for the statistical analysis increased from 816 (AD: 371, MCI: 445) to 1844 (AD: 580, MCI: 1264), which greatly enlarged the representation of the AD and MCI sample in the ADNI population. With increased sample size, a novel probabilistic classification model was introduced to infer an ADNI subject’s bilingualism when relevant demographic information and deterministic outcome were not readily available from the ADNI dataset. The weighted average OA for the bilinguals and the monolinguals was then computed, where the weights for the probabilistic labels were assigned based on the percentage of bilingualism in the general US population. Finally, a statistical analysis was performed to test whether any statistically significant correlation exists between the OA and the bilingualism of the AD and MCI subjects within the ADNI dataset. Findings: Our preliminary study demonstrates no significant statistical difference between the OA of the bilinguals and the monolinguals within the ADNI dataset. Thus, the monolingual speakers within the ADNI dataset do not statistically manifest earlier onset, as compared to the bilingual speakers, which is slightly inconsistent with some earlier statistical findings that bilingual speakers enjoy certain distinctive advantages, such as late onset of AD, as compared to monolingual counterparts.