Background and Purpose Chronic obstructive pulmonary diseases (COPD) are age-related, airflow-obstruction diseases mostly caused by cigarette smoke. However, the relationship between COPD and lung cellular senescence is still not fully understood. Here, we investigated how E3 ligase Pellino-1 mediated COPD and lung cellular senescence. Experimental Approach We used western blot, qPCR and co-IP assays to analyze the correlation of Pellino-1 and P21 in cells with or without silencing Pellino-1. Then we used flow cytometry, immunofluorescence staining and β- galactosidase assay to analyze the influences of silencing Pellino-1. Furthermore, we constructed COPD and aging models in vivo. Adenovirus of knock-down and overexpression Pellino-1 was used to infected mice. Immunohistochemistry and HE staining were used to analyze the lung pathology. Key Results Here, we first found that the E3 ubiquitin ligase Pellino-1 could bind to senescence marker p21 and modify p21 by K63-site ubiquitination and verified with silencing Pellino-1. Furthermore, we found that p21-mediated lung cellular senescence could be inhibited by silencing Pellino-1. Moreover, by constructing an adenovirus mouse model, we found that silencing Pellino-1 could inhibit COPD and inflammation via reduction of SASPs regulated by p21. Resistomycin, a potential Pellino-1 inhibitor, interrupts the interaction between Pellino-1 and p21, which accelerates the ubiquitin-dependent degradation of p21 and consequently inhibits lung cellular senescence and COPD progression. Conclusion and Implications Our study elucidated that inhibition of E3 ligase Pellino-1 exhibits therapeutic potential for treatment to attenuate the progression of lung cellular senescence and COPD.

Background: Ticagrelor is labelled as a reversible, direct-acting platelet P2Y12 receptor (P2Y12R) antagonist that is indicated clinically for the prevention of thrombotic events in patients with acute coronary syndrome (ACS). As with many antiplatelet drugs, ticagrelor therapy increases bleeding risk in patients which in emergency situations requires platelet transfusion although there is ongoing debate on its effectiveness following ticagrelor therapy. The aim of this study was to further examine the reversibility of ticagrelor at the P2Y12R. Methods: Studies were performed in human platelets with both P2Y12R-stimulated GTPase activity and platelet aggregation assessed. Cell-based bioluminescence resonance energy transfer (BRET) assays were also undertaken to assess G protein subunit activation downstream of P2Y12R activation. Results: Initial studies revealed a range of P2Y12R ligands including ticagrelor displayed inverse agonist activity at the P2Y12R. Of these only ticagrelor was resistant to wash-out. In both human platelets and cell-based assays, washing failed to reverse ticagrelor-dependent inhibition of ADP-stimulated P2Y12R function in contrast to other P2Y12R antagonists. The P2Y12R agonist 2MeSADP, which was also resistant to wash-out, was able to effectively compete with ticagrelor. In silico docking revealed that ticagrelor and 2MeSADP penetrated more deeply into the orthosteric binding pocket of the P2Y12R than other P2Y12R ligands. Conclusion: Ticagrelor binding to the P2Y12R is prolonged and more akin to that of an irreversible antagonist especially versus the endogenous P2Y12R agonist ADP. This study highlights the potential clinical need for novel ticagrelor reversal strategies in patients with spontaneous major bleeding and bleeding associated with urgent invasive procedures.

Introduction: Assessment of and intervention for sleep-disordered breathing and malnutrition are related to respiratory management for preventing recurrent respiratory tract infections (RRTIs) and acute respiratory failure (ARF) in children with spinal muscular atrophy (SMA). However, the specific standard has not been clarified. Purpose: The study aimed to obtain the risk factors and the predictive index for RRTIs and/or ARF in children with SMA. Methods: In this retrospective study, the differences in clinical characteristics in patients with or without RRTIs and ARF were compared, and binary logistic regression analysis was carried out. The best cutoff points of the positive predictive index were obtained. Results: Type 1 (OR = 4.12, 95% CI 1.30-13.07, P =.016) and apnea hypopnea index (AHI) (OR = 1.14, 95% CI 1.05-1.24, P =.001) were risk factors, while body mass index z score (BMIz) (OR = 0.68, 95% CI 0.49-0.94, P =.018) and mean pulse oxygen saturation (MSpO 2) (OR = 0.67, 95% CI 0.50-0.91, P =.010) were protective factors. The sensitivity and specificity of the standard of MSpO 2 < 96% and AHI > 10 events/h or BMIz < -1 with the occurrence of RRTIs and/or ARF were 0.513 and 0.957, respectively. Conclusion: SMA Type 1, BMIz, AHI and MSpO 2 should be used to estimate the risk for RRTI or ARF in children with SMA. MSpO 2 < 96%, and AHI > 10 events/h or BMIz < -1 should be used as the intervention standard.

A document by S. Choudhary. Click on the document to view its contents.

A document by Amjad Saleh El-Amoush. Click on the document to view its contents.

Background: Hemophagocytic lymphohistiocytosis (HLH) frequently is a fatal disorder of immune system, mainly manifesting as uninterrupted fever, hepatosplenomegaly, pancytopenia, hemophagocytosis, central nervous system (CNS) involvement, and elevation of HLH related biomarkers. Hematopoietic stem cell transplantation (HSCT) is the sole curative therapy for this disease. Methods: Retrospective study of outcomes in patients who underwent HSCT in a single center. Results: Eight patients (four males), with a median age at diagnosis was 3.3 years (range, 1.2 to 13.4) and at transplantation was 2.9 years (range, 0.8 to 13.0), received standard HLH chemotherapy before HSCT. Two patients were in active disease (AD). All received busulfan-based myeloablative conditioning (MAC) regimen. Four (50%) patients received peripheral blood stem cells (PBSC), four (50%) received umbilical cord blood (UCB). Two (25%) patients who received UCB first underwent second transplantation. Three (37.5%) patients had acute Graft-versus-host disease (GVHD), and one (12.5%) had chronic GVHD. Only one (12.5%) patient died due to multiple organ dysfunction syndrome (MODS). Conclusion: Active disease and mixed chimerism were the fatal prognostic factors. Graft failure was a part of the significant disadvantages of UCB. In combination with standard HLH therapy, HSCT could be an effective means of prolonging survival and curing pediatric HLH. To some extent, UCB is a good option in the absence of PBSC.

Pulmonary embolism is a potentially fatal condition that encountered in practice and mandates prompt identification and management. If left untreated, a delay in diagnosis can be catastrophic for the patient and carry a significant risk of death.

Chylous ascites following trauma in children is very rare, and to the best of our knowledge, there are very few reports in this regard. Here, we report a 7-year-old girl who was referred to our center with CA after a car accident.

Background: The 5th wave of the COVID-19 pandemic in Hong Kong was dominated by the omicron variant, which may have more upper airway involvement affecting children. This pilot study aims at analyzing any associations between the COVID-19-omicron-variant and croup in children. Methods: This retrospective study reviewed electronic medical records of patients admitted to Tuen Mun Hospital of Hong Kong from 1 January 2018 to 31 March 2022 with diagnostic code of croup (ICD-10 code J05.0). Patients were categorized into non-COVID period (1 January 2018 - 31 December 2019); COVID-pre-omicron period (1 January 2020 - 31 December 2021) and COVID-omicron period (1 January 2022- 31 March 2022). Disease associations and severity were compared through incidence rates, Westley Croup Severity Score, length of hospital stay, medications use, respiratory support and intensive care unit admissions. Results: The rate of infection of COVID-19 in croup patients admitted during COVID-omicron period (90%) was significantly higher than those in the COVID-pre-omicron period (3.6%, p< 0.001). They also had a higher Westley Score (moderate + severe disease: COVID-omicron: 56.7%; COVID-pre-omicron: 22.4%; p=0.004; non-COVID: 24.8%, p< 0.001), longer hospital stay (median: COVID-omicron 3.00 days ; COVID-pre-omicron:2.00 days, p<0.001, non-COVID: 2.00 days, p=0.034) , and higher dexamethasone requirements (mean : COVID-omicron = 0.78mg/kg; COVID-pre-omicron= 0.49mg/kg, p < 0.001; non-COVID =0.58mg/kg , p=0.001) while compared to those of the COVID-pre-omicron period and non-COVID period. Conclusion: The omicron variant of COVID-19 is a significant contributing factor to croup and can lead to more severe disease in children of Hong Kong.

Using subterranean fauna in the Canary Islands as a simplified natural laboratory, we explored how the interplay of eco-evolutionary processes shape taxonomic and functional diversity patterns in oceanic archipelagos through geological times. First, we demonstrated an overall convergence in the trait spaces of subterranean communities across islands, yet with variability according to each island's ontogenetic state---young, mature, or senescent. Next, we showed that the reduced species contribution to the island's traits space in mature islands is a consequence of an optimisation of the use of the available niche space driven by species interactions. Finally, we link those lines of evidence showing that species interactions select a non-random combination of traits in mature islands. Collectively, our results provided a mechanistic description of the drivers of diversity in oceanic islands by suggesting causal relationships between species functional properties and island diversity metrics accounting for their geological age.

Fault detection is crucial in smart grid control and monitoring operations. The use of smart meters leads to appearance of a large amount of digital data whose conventional and chronological techniques are not efficient enough for processing and decision-making. In this paper, a novel data analysis model based on deep learning and neuro-fuzzy algorithm is proposed for detection and classification of faults in a smart grid. First, the Long Short Term Memory (LSTM) based deep learning model is applied for training the data samples extracted from the smart meters. Then, the Adaptive Neuro Fuzzy Inference System (ANFIS) is implemented for fault detection and classification from the trained data. With this intelligent method proposed, single-phase, two-phase and three-phase faults can be identified using a restricted amount of data. To verify the effectiveness of our methodology, an intelligent model of the IEEE 13-node network is used. The results indicate that the combined ANFIS-LSTM deep learning model outperforms existing machine learning methods in the literature in terms of accuracy for fault detection and classification.

Protein structures are stabilized by several types of chemical interactions between amino acids, which can compete with each other. This is the case of chalcogen and hydrogen bonds formed by the thiol group of cysteine, which can form three hydrogen bonds with one hydrogen acceptor and two hydrogen donors and a chalcogen bond with a nucleophile along the extension of the C-S bond. A survey of the Protein Data Bank shows that hydrogen bonds are about 40-50 more common than chalcogen bonds, suggesting that they are stronger and, consequently, prevail, though not always. It is also observed that frequently a thiol group that forms a chalcogen bond is also involved, as a hydrogen donor, in a hydrogen bond.

The author's intent is to bring one such case to focus wherein just mere lack of knowledge and casual approach towards one's own health having undiagnosed underlying blood coagulation disorder led to catastrophic sequence of events, leaving behind a cautionary learning tale from a loss of life.

Mature ovarian Cystic teratoma or dermoid cyst is one of the most common benign ovarian neoplasms that can be found in different age groups and in various sizes. It is important to diagnose and treat this problem as soon as possible because of its complications especially malignancy transformation.

A healthy 48-years-old male patient was referred to our department to take radiographs of a displaced implant. Upon radiographic evaluation, it was unveiled that the implant has migrated to the nasal cavity and is trapped under the middle concha. The implant was removed under endoscopy through the right nostril.

Objective: To evaluate the efficacy of sacubitril/valsartan for the treatment of patients with chronic heart failure (CHF) after cardiac valve surgery (CVS). Methods: Data of 259 patients who underwent CVS due to organic heart disease, and who were admitted to the hospital with CHF from January 2018 to December 2020, were collected. The patients were divided into Group A (treatment with sacubitril/valsartan) and Group B (treatment without sacubitril/valsartan). The duration of treatment and follow-up was 6 months. Prior-treatment clinical characteristics, post-treatment data, mortality, and follow-up data of the two groups were analyzed. Results: The total effective rate of Group A was higher than that of Group B (82.56% versus 65.52%, P < 0.05). The left ventricular ejection fraction (LVEF) was improved in both groups (11.14 ± 10.16 versus 7.15 ± 11.18, P = 0.004). The left ventricular end-diastolic/-systolic diameter (LVEDD/LVESD) in Group A decreased more than that in Group B (3.58 ± 9.21 versus 0.27 ± 14.44, P=0.026; 4.21 ± 8.15 versus 1.14 ± 12.12, P=0.016, respectively). The N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) in both groups decreased (1305.65 ± 2000.85 versus 675.91 ± 1649.84, P=0.012). The systolic and diastolic blood pressure (SBP/DBP) in Group A decreased more than that in Group B (13.13 ± 23.98 versus 1.81 ± 10.89, P < 0.001; 8.28 ± 17.79 versus 2.37 ± 11.41, P = 0.005, respectively). Liver and renal insufficiency, hyperkalemia, symptomatic hypotension, Angioedema or acute heart failure have no statistical differences between the two groups. Conclusion: Sacubitril/valsartan can effectively improve the cardiac function of CHF patients after CVS by increasing LVEF, reducing LVEDD, LVESD, NT-proBNP and BP, with good safety.

For donation after circulatory death, procurement is performed after the heart has arrested. This technique has been employed and adopted by clinicians to overcome the shortage of available hearts for transplant. Warm ischemia time plays a pivotal role in the survival outcome of the heart recipients. We describe a fast and safe technique to flush the heart during recovery from circulatory death donors in order to shorten the warm ischemia time.

The blue shark Prionace glauca is a top predator with one of the widest geographic distributions of any shark species, yet classified as critically endangered in the Mediterranean Sea, and Near Threatened globally. Previous genetic studies did not reject the null hypothesis of a single global population across the worldwide species range. Blue shark situation was proposed as a possible archetype of the ‘grey zone of population differentiation’, coined to designate cases where population structure may be too recent or too faint to be detected using a limited set of markers. Here, blue shark samples collected throughout its global range were sequenced using a specific ddRAD method (DArTseq; Georges et al. 2018), which recovered 37,655 genome-wide single nucleotide polymorphisms (SNPs). Two main groups emerged, with Mediterranean Sea and Northern Atlantic samples significantly differentiated from the Indo-west Pacific samples. Significant pairwise FST values indicated further genetic differentiation within the Atlantic Ocean, and between the Atlantic Ocean and the Mediterranean Sea. Reconstruction of recent demographic history suggested the divergence between northern and southern oceanic populations emerged about 500 generations ago and revealed a drastic reduction in effective population size from a large ancestral population. Our results illustrate the power of high-density genome scans to detect population structure and reconstruct demographic history in highly migratory marine species. As the management of the blue shark fishery, either as target or as bycatch, does not account for this delineation, we strongly recommend that the results presented here be considered in future stock assessment and management plans.

The idea of lacunary statistical convergence sequences, which is a development of statistical convergence, is examined and expanded in this study on L − fuzzy normed spaces, which is a generalization of fuzzy spaces. On L − fuzzy normed spaces, the definitions of lacunary statistical Cauchy and completeness, as well as associated theorems, are provided. The link between lacunary statistical Cauchyness and lacunary statistical boundedness with regard to L − fuzzy norm is also shown.

The purpose of this paper is to give a necessary and sufficient condition for the existence and non-existence of global solutions of the following semilinear parabolic equations \[ u_{t}=\Delta u+\psi(t)f(u),\,\,\mbox{ in }\Omega\times (0,t^{*}), \] under the Dirichlet boundary condition on a bounded domain. In fact, this has remained as an open problem for a few decades, even for the case $f(u)=u^{p}$. As a matter of fact, we prove:\\ \[ \begin{aligned} &\mbox{there is no global solution for any initial data if and only if }\\ &\mbox{the function } f \mbox{ satisfies}\\ &\hspace{20mm}\int_{0}^{\infty}\psi(t)\frac{f\left(\epsilon \,\left\| S(t)u_{0}\right\|_{\infty}\right)}{\left\| S(t)u_{0}\right\|_{\infty}}dt=\infty\\ &\mbox{for every }\,\epsilon>0\,\mbox{ and nonnegative nontrivial initial data }\,u_{0}\in C_{0}(\Omega). \end{aligned} \] Here, $(S(t))_{t\geq 0}$ is the heat semigroup with the Dirichlet boundary condition.

This work is about the goldbach conjecture . Here i have attempted to disprove it using different methods, just to brief it it involves ramanujan's derivation of riemanns's zeta function. I would request you to kindly review and let me know the feedback. Thank you

In this paper, we are concerned with an integral system $$ \left\{ \begin{aligned} &u(x)= W_{\beta,\gamma}(u^{p-1}v)(x), \ u>0 \ \text{in} \ R^{n},\\ &v(x)=I_{\alpha}(u^{p})(x), \ v>0 \ \text{in} \ R^{n}, \end{aligned} \right. $$ where $p>0,$ $0<\alpha, \beta\gamma1$. Base on the integrability of positive solutions, we obtain some Liouville theorems and the decay rates of positive solutions at infinity. In addition, we use the properties of the contraction map and the shrinking map to prove that $u$ is Lipschitz continuous. In particular, the Serrin type condition is established, which plays an important role to classify the positive solutions.

The geometrical structures, stabilities and electronic properties of bimetallic mononuclear LinClK(0,+1) (n=1-6) clusters were studied within the density functional theory. From the ground state geometries, the Cl atom prefers the apex position and the K atom is at either side position or at surface. The dissociation energy, second order energy difference and GapHL (HOMO-LUMO gap) points out that LinClK(n=2,4,6) and the LinClK+(n=1,3,5) clusters are more stable. According to their ionization energies, the clusters can be classified as superalkalis, but the systematic study signifying that noticeable ionisation energy difference appears between the smallest bimetallic mononuclear superalkali compound (LiClK) and rest of superalkali species. Upon ionisation, the detached electron is from K atom. The delocalised electrons except the LiClK+ point out that the clusters are hyperlithiated clusters. The delocalization type of 3c/2e is responsible from the higher stability of the closed shell clusters.

A portion of the west of Mexico City is a densely populated area located in an abrupt topography, whose volcano-sedimentary materials increase the likelihood of landslides. This study uses Seismic Refraction Tomography (SRT) and Ambient Noise Tomography (ANT) methods to estimate the extent of landslide-prone materials at a test site. We exploited the geometry of a quadrangular array of surface sources and receivers to generate a Vp tomography image of the bedrock and surface-wave group-velocity tomographies of SRTand ANT in the frequency range of 6 to 26 Hz. We found that the best velocities correlation between the two methods is an average frequency of 24 Hz. The results show the areas of low velocity associated with materials that have lost their resistance due to the increase in pore pressure (Vs < 100 m/s) and the areas where eventually more landslides will occur (120 < Vs < 200 m/s) if mitigation work is not carried out. The most stable zones correspond to materials with velocity values greater than 250 m/s that overlap a substratum at an average depth of 8 m. In the case of a high risk of landslide, when it is not advisable to perform active source experiments, ANT can provide good results to determine the extension of the sliding materials.