The meaning of life

In this paper we interest concerns an integro-differential equation of Volterra when the derivative of the solution appears under the sign of integration in a non-linear way. The derivation is the Caputo-Fabrizio Fractional Derivative (CF-FD), which increases the interest of this study. we built Lipchitz conditions to obtain the existence and uniqueness of the solution in a Banach space specific to the derivative of Caputo. The analytical study is followed by a complete numerical study.

keratosis pilaris (KP) is an autosomal dominant disorder characterized by keratotic follicular papules with varying degrees of perifollicular erythema. Keratosis pilaris affects up to half of normal children and up to three-quarters of children with ichthyosis vulgaris. Most commonly it affects children with atopic eczema.

Efficiently delivering nucleic acid into mammalian cells is essential to overexpress genes for assessing gene functions. Human bone marrow stem cells (hBMSCs) are the most studied tissue-derived stem cells. Adeno-associated viruses (AAVs) have been used to deliver DNA into hBMSCs for various purposes. This study optimized the AAV transduction protocol for high-efficiency DNA delivery into hBMSCs. hBMSCs were infected with different serotypes of AAVs containing green fluorescence (eGFP) reporter driven by the CMV promoter. GFP was monitored in the infected cells. Cells were collected at designated time points after the infection for RT-PCR to assess eGFP mRNA. The results indicated that the order of transduction efficiency of the AAV serotypes was AAV2 > AAV2.7 > AAV6 > AAV6.2 > AAV1 > AAD-DJ. AAV2 could achieve almost 100% transduction at the MOI greater than 100K. Over 90% of cells could be transduced at 20K to 50K MOI. About 80% transduction was seen at MOIs of 10K and 15K. The eGFP expression reached the maximum about15- 25 days post-AAV2 infection. High levels of transcription were still detectable at day 30 post-infection. We conclude that AAV2 and AAV2.7 can efficiently deliver transgene into hBMSCs for sustained expression over one month.

Kaposi's sarcoma is a common cancer associated with HIV infection. Since the COVID-19 pandemic, the prevalence of this pathology has increased. We report a case of a 33-year-old patient who presented with Kaposi's sarcoma associated with Covid-19 and HIV coinfection. It promotes the progression of cancers and increases mortality.

Geraniol is an important contributor to the pleasant floral scent of tea products and one of the most abundant aroma compounds in tea plants; however, its biosynthesis and physiological function in response to stress in tea plants remain unclear. Here, we studied eight terpene synthases with expression levels that were correlated with geraniol accumulation in different tissues of tea plants. The proteins encoded by the full-length terpene synthase ( CsTPS1) and its alternative splicing isoform ( CsTPS1- AS) could catalyze the formation of geraniol when GPP was used as a substrate in vitro, whereas the expression of CsTPS1- AS was only significantly induced by Colletotrichum gloeosporioides and Neopestalotiopsis sp. infection. Silencing of CsTPS1 and CsTPS1- AS resulted in a significant decrease in the geraniol content in tea plants. The geraniol content and antifungal activity of tea plants were compared when CsTPS1 and CsTPS1- AS were silenced. Down-regulation of the expression of CsTPS1- AS reduced the accumulation of geraniol, and the silenced tea plants exhibited greater susceptibility to pathogen infection than control plants. However, the geraniol content and pathogen resistance of CsTPS1-silenced plants and control plants did not significantly differ. Further analysis showed that silencing of CsTPS1- AS led to a decrease in the expression of the defense-related genes PR1 and PR2 and the expression of SA pathway-related genes in tea plants, which increased the susceptibility of tea plants to pathogenic fungal infections . Both in vitro and in vivo results indicated that CsTPS1 is involved in the regulation of geraniol formation and plant defense via alternative splicing in tea plants. The results of this study provide new insights into geraniol biosynthesis and highlight the role of monoterpene synthases in modulating plant disease resistance via alternative splicing.

Introduction: L‑Asparaginase is an essential chemotherapeutic agent in the therapy of Acute Lymphoblastic Leukemia (ALL), which has led to improvement in survival. In low and middle-income countries like India, the outcomes in ALL are inferior compared to the published literature, one of the cause of which are believed to be due to the inferior quality of bioequivalent Asparaginase. The following survey attempts to understand the practice of using this agent among oncologists treating children with cancer in our country. Methods: The researchers designed a structured online questionnaire comprising 25 aspects of L-Asparaginase usage in the study. The questionnaire was directed to the healthcare providers involved in treating children with cancer in India. Results: Of the total 80 responses recorded, 51 (64%) respondents had more than five years of experience in pediatric oncology and were treating at least 5-10 newly diagnosed ALL patients per month. Forty-one (51%) respondents utilized Native Asparaginase, and 21 (26.3%) oncologists used PEGylated-Asparaginase exclusively. The most common route of administration was the intramuscular route (66.3%). Seventy percent of respondents utilized Native form at a dose of 10,000IU/m 2 and 20% at 6000IU/m 2. The amounts used for PEGylated L-Asparaginase were 1000IU/m 2, 2500IU/m 2, and variable doses in 48%, 40%, and 10% of responses, respectively. Though Serum Asparaginase assay (SAA) was not measured routinely in most of the centres, 39 (48.8%) healthcare providers perceived performing SAA helps to make the clinical decision. Conclusion: This survey shows a wide variation in L-Asparaginase usage among healthcare providers caring for children with cancer in our country. As L-Asparaginase is the pivotal component of ALL therapy, uniformity in its usage and dosing with the possibility of monitoring SAA due to the quality of bioequivalent may be one of the critical steps towards improving outcomes in ALL in our country.

Cloud computing is the next stage in evolution of the internet, which provides large amounts of computing and storage to customers provisioned as a service over the internet. However, cloud computing faces so many security challenges due to the possible compromise or byzantine failures. In this paper, we focus on Ensuring data storage security in cloud computing, which is an important aspect of Quality of Service (QoS). We propose an effective and flexible distribution verification protocol to address data storage security in cloud computing. In this protocol, we rely on erasure code for the availability, reliability of data and utilize token precomputation using Sobol Sequence to verify the integrity of erasure coded data rather than Pseudorandom Data in existing systems. Unlike prior works, our scheme provides more security to user data stored in cloud computing. The performance analysis shows that our scheme is more secure than existing systems against Byzantine failure, unauthorized data modification attacks, and even cloud server colluding attacks.

Although the COVID-19 lockdowns in 2020 had some environmental benefits, the pandemic’s impact on the global economy has also had conservation repercussions, especially in biodiverse nations. Ecuador, which is heavily reliant on petroleum, agricultural exports, and ecotourism, experienced a rise in poverty in response to pandemic shutdowns. In this study, we sought to quantify levels of illegal timber extraction and poaching before and after the start of COVID-19 lockdowns throughout two protected areas (Reserva Jama Coaque [JCR] and Reserva Bosque Seco Lalo Loor [BSLL]) in the endangered Pacific Forest of Ecuador. We analyzed chainsaw and gunshot acoustic data recorded from devices installed in the forest canopy from December 2019 to March 2020 and October 2020 to March 2021. Results from generalized linear mixed effects models indicated less chainsaw activity before lockdowns (post.lockdown = 0.571 + 0.196 SE, p-value = 0.004), although increased average rainfall also seemed to negatively affect chainsaw activity (avg.rainfall = -0.005 + 0.001 SE, p-value < 0.001). Gunshots were too infrequent to conduct statistical models; however, 87% of gunshots were detected during the ‘lockdown’ period. Observational data collected by rangers from these protected areas also noted an increase in poaching activities beginning mid to late 2020 and persisting into 2021. These results add to the steadily growing literature indicating an increase in environmental crime, particularly in biodiverse nations, catalyzed by COVID-19-related economic hardships. Identifying areas where environmental crime increased during pandemic lockdowns is vital to address both socioeconomic drivers and enforcement deficiencies to prevent further biodiversity loss and disease outbreaks and to promote ecosystem resilience. Our study also demonstrates the utility of passive acoustic monitoring to detect illegal resource extraction patterns, which can inform strategies such as game theory modeling for ranger patrol circuits and placement of real-time acoustic detection technologies to monitor and mitigate environmental crimes.

Virus infections and T cell-mediated drug hypersensitivity reactions (DHR) can influence each other. In most instances, systemic virus infections appear first. They may prime the reactivity to drugs in two ways: First, by virus-induced second signals: certain drugs like β-lactam antibiotics are haptens and covalently bind to various soluble and tissue proteins, thereby forming novel antigens. Under homeostatic conditions, these neo-antigens do not induce an immune reaction, probably because co-stimulation is missing. During a virus infection, the hapten-modified peptides are presented in an immune-stimulatory environment with co-stimulation. A drug-specific immune reaction may develop and manifest as exanthema. Second, by increased pharmacological interactions with immune receptors (p-i) : drugs tend to bind to proteins and may even bind to immune receptors. In the absence of viral infections, this low affine binding may be insufficient to elicit T cell activation. During a viral infection immune receptors are more abundantly expressed and allow more interactions to occur. This increases the overall avidity of p-i reactions and may even be sufficient for T cell activation and symptoms. There is a situation, where the virus-DHR sequence of events is inversed: in drug reaction with eosinophilia and systemic symptoms (DRESS), a severe DHR can precede reactivation and viremia of various herpes viruses. One could explain this phenomenon by the massive p-i mediated immune stimulation during acute DRESS, which coincidentally acvitates many herpes virus-specific T cells. Through p-i stimulation, they develop a cytotoxic activity with killing of herpes peptide-expressing cells and release of herpes viruses. These concepts could explain the often transient nature of DHR occurring during viral infections and the often asymptomatic herpes-virus viraemia after DRESS.

Elymus breviaristatus (family Triticeae), a rare grass species with excellent resistance and ecological importance, is narrowly distributed on the Qinghai-Tibet Plateau (QTP). Populations of E. breviaristatus are declining due to habitat fragmentation, and thus far, characteristics of genetic differentiation and adaptive responses to climate change remain poorly understood in this species. Here, we explored the genetic structure of 18 natural populations (269 individuals) in the transition zone between Tibet and the Hengduan Mountains using 15 expressed sequence tag (EST)-SSR primer pairs and identified possible barriers to gene flow that might have caused genetic discontinuities. Additional analyses were performed to identify the environmental factors affecting genetic diversity and to test whether the patterns of genetic variation among populations were more consistent with the isolation by distance (IBD) or isolation by environment (IBE) model. Multiple measures of genetic diversity revealed that intra-population genetic variation was low, while inter-population genetic variation was high. Clustering, structure, and principal coordinate analyses identified three genetic groups: (a) Eastern Qamdo, (b) Nagqu and Western Qamdo, and (c) Lhasa and Nyingchi. A clear physical barrier to gene flow was formed by the Yarlung Zangbo Grand Canyon and the Tanggula Mountains. We found that both IBD and IBE contributed to the observed patterns of genetic variation, indicating that the process of population differentiation was affected by complex mechanisms. In addition, four precipitation-related variables significantly affected population genetic variation, especially in extremely cold and dry habitats. Overall, our results emphasized the genetic fragility of E. breviaristatus populations and showed that this species requires attention, as future climate changes and human activities may further threaten its survival. In addition, the genetic differences among E. breviaristatus populations should be considered when formulating conservation measures for E. breviaristatus populations in the study area.

Resting stages of aquatic organisms that accumulate in the sediment over time are an exceptional resource that allows direct insights into past populations and addressing evolutionary questions. This is of particular interest in taxa that have recently faced environmental changes such as the Daphnia longispina species complex, a keystone zooplankton group in European freshwater ecosystems. However, genomic analysis might be challenging as many of these resting stages are very small and the DNA might be degraded. To reliably allow the resequencing of single Daphnia resting eggs from different sediment layers and characterize genomic changes through time, we performed whole genome amplification to obtain DNA amounts suitable for genome re-sequencing and tested multiple protocols involving egg isolation, whole genome amplification kits and library preparation. A pre-sequencing contamination screening was developed to quickly assess possible contamination. In total, we successfully amplified and sequenced nine genomes from Daphnia resting eggs that could be identified as Daphnia longispina species. We analyzed the genome coverage and SNP calling of these samples to optimize this method for future projects involving population genomic investigation of the resting egg bank.

A unified phase-field theory is introduced to describe crack initiation and early crack growth due to pitting corrosion of pipelines in contact with near-neutral pH groundwater. The model incorporates a formulation that accounts for stochastic corrosion-induced crack nucleation events at pit sites. This approach supplies a modeling framework to handle the combined effects of electrochemical transformation of the original metal, hydrogen diffusion and resulting embrittlement of the original metal, and mechanical stresses. This is a robust computational approach to tracking the evolving metalelectrolyte interface and embrittlement regions. It was confirmed that dissolved hydrogen into the material promotes crack initiation over a wide potential range and that pitting corrosion, as a precursor of stress corrosion cracking, has a recognizable influence on strength over time. It is expected that this work provides the ground for modeling the pit-to-crack transition required to effectively control very slow crack-in-colonies in pipelines.

Leadless pacemaker implantation (LPI) has fewer device complications and reduced chance of infection compared to conventional pacemakers. Dextrocardia with situs viscerum inversus (DC+SVI) is a rare condition, which seldom leads to cardiac complications. However, its presence poses a challenge to operators in cardiac procedures. LPI reports in DC patients are scarce. We report a case of LPI in a DC+SVI patient, followed by a brief but comprehensive literature review.

Biobutanol produced in acetone-butanol-ethanol fermentation at batch mode cannot compete with chemically derived butanol because of the low reactor productivity. Continuous fermentation can dramatically enhance productivity and lower capital and operating costs but are rarely used in industrial fermentation because of increased risks in culture degeneration, cell washout, and contamination. In this study, cells of the asporogenous Clostridium acetobutylicum ATCC55025 were immobilized in a single-pass fibrous-bed bioreactor (FBB) for continuous production of butanol from glucose and butyrate at various dilution rates. Butyric acid in the feed medium helped maintaining cells in the solventogenic phase for stable continuous butanol production. At the dilution rate of 1.88 h -1, butanol was produced at 9.55 g/L with a yield of 0.24 g/g and productivity of 16.8 g/L∙h, which was the highest ever achieved for biobutanol fermentation and an 80-fold improvement over the conventional ABE fermentation. The extremely high productivity was attributed to the high density of viable cells (~100 g/L at >70% viability) immobilized in the fibrous matrix, which also enabled the cells to better tolerate butanol and butyric acid. The FBB was stable for continuous operation for an extended period of over one month.

Background: Decreasing right ventricular (RV) and left ventricular (LV) function after surgical or transcatheter aortic valve replacement (SAVR or TAVR, respectively) is an important risk factor for morbidity and mortality. Although transapical (TA)-TAVR is an independent risk factor for post-procedural mortality, limited knowledge is available regarding long-term changes in RV and LV function. The study aimed to evaluate LV and RV performance following four different AVR procedures, including TA-, transfemoral (TF)-TAVR, and SAVR with and without coronary artery bypass grafting (±CABG). Methods: Patients with severe AS were consecutively included and assigned to TA-TAVR, TF-TAVR, or SAVR ±CABG groups. A total of 130 patients underwent preoperative conventional and strain-rate-imaging echocardiography, with similar controls in the period between 6 and 12 months after the procedure. Results: After AVR, NYHA classes III and IV were reduced from 105 (81%) to 6 (5%) patients. While most of the systolic and diastolic functional parameters indicated improved LV function in the TF-TAVR and both SAVR groups, LV function did not significantly change after TA-TAVR. The right ventricular functional parameters were unchanged or even improved equally after TA-TAVR and TF-TAVR, while they were significantly reduced after SAVR. The Cardiac Index (CI) improved significantly after TF-TAVR from 2.3±0.7 to 2.6±0.7, while staying unchanged after TA-TAVR and SAVR±CABG. Conclusion: This study demonstrated significant changes in LV and RV systolic and diastolic function with functional improvement or deterioration depending on the type of aortic valve replacement. The most significant improvement in CI was observed after TF-TAVR, which is the least invasive procedure.

Isoprenoids are a large family of natural products with diverse structures, which allow them to play diverse and important roles in the physiology of plants and animals. They also have important commercial uses as pharmaceuticals, flavouring agents, fragrances, and nutritional supplements. Recently, metabolic engineering has been intensively investigated and emerged as the technology of choice for the production of isoprenoids through microbial fermentation. Isoprenoid biosynthesis typically originates in plants from acetyl-coA in central carbon metabolism, however, a recent study reported an alternative pathway, the Isopentenol Utilization pathway (IUP), that can provide the building blocks of isoprenoid biosynthesis from affordable C5 substrates. In this work, we expressed the IUP in Escherichia coli to efficiently convert isopentenols into geranate, a valuable isoprenoid compound. We first established a geraniol-producing strain in E. coli that uses the IUP. Then, we extended the geraniol synthesis pathway to produce geranate through two oxidation reactions catalysed by two alcohol/aldehyde dehydrogenases from Castellaniella defragrans. The geranate titer was further increased by optimizing the expression of the two dehydrogenases and also parameters of the fermentation process. The best strain produced 764 mg/L geranate in 24 h from 2 g/L isopentenols (a mixture of isoprenol and prenol). We also investigated if the dehydrogenases could accept other isoprenoid alcohols as substrates.

Porcine circovirus type 2 (PCV2) has been identified as the causal agent of postweaning multisystemic wasting syndrome (PMWS), an economically important multifactorial disease of the swine industry worldwide. This research designed a dual nested polymerase chain reaction (PCR) detection method to simultaneously monitor porcine circovirus type 2 (PCV2) and PCV3. The main applications for this protocol focused on technical support for its use during early warning surveillance of PCV and its application for the investigation of pathogenic ecology for large-scale pig farms in some areas of China. Two pairs of primers were designed based on the conserved regions of both PCV2 and PCV3 strain genes included in GenBank. This resulted in a highly sensitive detection method with good specificity, which was constructed by optimizing the reaction conditions and testing for specificity, sensitivity, and coincidence rate. Next, 15,130 systematic early warning and clinical samples were assessed using the developed methods. The limit of detection (LoD) of sensitivity for PCV2 and PCV3 was ten copies/mL for both viruses. There was no cross-reaction with any other porcine pathogens tested and no non-specific amplification. The coincidence and repetition rates were 100%. Through the systematic and clinical sampling, 15,130 samples from 30 large-scale pig farms in eight provinces (Hubei, Hunan, Henan, Jiangxi, Shanxi, Guangdong, Hainan, and Heilongjiang) were subjected to early warning surveillance and/or clinical diagnosis. The results revealed that the overall positive rates of PCV3 and PCV2 were 0% and 28.29%, respectively, with the lowest level [8.31% (133/1,600)] recorded in Jiangxi province. The highest carrying rate [42.36% (762/1,799)] was observed in Hainan province. Pigs at different ages displayed varying carrying rates: fattening pigs and reserve pigs had the highest and the lowest carrying rates at 65.01% (901/1,386) and 6.87% (98/1,426), respectively. In addition, the detoxification rates of colostrum, semen, and nasal, anal, and vulval swabs were tested. The colostrum, anal swabs, and semen had higher toxicity rates of 26.65%, 25.30%, and 22.71%, respectively; these were followed by the vulval and nasal swabs that had toxicity rates of 15.47% and 12.81%, respectively. Furthermore, a high blood virus-carrying rate was detected in moribund pigs, especially in pigs with fever and red skin. As to the virus-carrying rate in the pig organs received from clinical necropsy, the highest rate was found in placental tissue, followed by the kidneys, and the virus also was detected in lymphoid organs, liver, stomach, and intestines. The PCV2-positive samples were sequenced and compared to reveal the molecular epidemic dynamics of PCV2 and disclose the genetic backgrounds of these epidemic strains in China. These results provided support for tracing the sources of virus transmission in future outbreaks. The results showed that the gene sequences of the 24 PCV2 strains tested showed 95.36 to 100% homology among the detected strains and 95.46 to 99.98% among the detected strains and the reference strains. Nine strains belonged to PCV2a, seven belonged to PCV2b, two belonged to PCV2c, and six strains belonged to PCV2d.

Background: Dysphagia following cardiac surgery is common and associated with adverse outcomes. Among patients receiving left ventricular assist device (LVAD), we evaluated the impact of fiberoptic endoscopic evaluation of swallowing (FEES) on outcomes. Methods: A single-center pilot study was conducted in adults (≥18 years of age) undergoing durable LVAD (February 2019-January 2020). Six patients were prospectively enrolled, evaluated, and underwent FEES within 72 hours of extubation—they were compared to 12 control patients. Demographic, surgical, and postoperative outcomes were collected. Unpaired two-sided t-tests and Fisher’s Exact tests were performed. Results: Baseline characteristics were similar between groups. Intraoperative criteria including duration of transesophageal echo (314 ± 86 min) and surgery (301 ± 74 min) did not differ. Mean time of intubation was comparable (57.3 vs. 68.7 hours, p=0.77). In the entire cohort, 30-day, 1-year, 2-year, and 3-year mortality were 0%, 5.6%, 5.6%, and 16.7%, respectively. Sixty-seven percent of the patients that underwent FEES had inefficient swallowing function. The FEES group trended to a shorter hospital length of stay (LOS) (29.1 vs. 46.6 days, p=0.098), post-implantation LOS (25.3 vs 30.7 days, p=0.46), and lower incidence of postoperative pneumonia (16.7% vs. 50%, p=0.32) and sepsis (0% vs. 33.3%, p=0.25). Conclusions: FEES did not impact 30-day, 1-year, 2-year, or 3-year mortality. Patients who underwent FEES trended toward shorter LOS, and lower postoperative pneumonia and sepsis rates, though not statistically significant. A higher incidence of dysphagia among patients undergoing FEES despite comparable baseline risk factors with controls suggests FEES may detect subclinical dysphagia.

The long-term outcome of patients undergoing mitral valve repair (MVr) is based on what happens during the more or less 60 minutes of aortic cross clamping necessary to transform a leaking valve in a well-functioning one. As a consequence, the experience of the surgeon performing the procedure is the only determinant of the success rate that deserves to be taken into account. It is clear from the literature that the number of cases/year is inversely related to the number of early and late deaths, of repair failures and of reoperations. However, there is no agreement on the minimum caseload/year that represents the threshold to identify surgeons that can perform or not MVr. This problem then cannot be regulated by specific guidelines of by Scientific Societies, but only by the ethical perception we have of our profession.

Late complications of COVID -19 infection are as important as the acute phase problems . A young woman with a history of COVID-19 infection and concomitant visual problems was admitted with exacerbation of dyspnea . During the admission, pulmonary embolism , myocarditis and fungal endocarditis were detected .

Objective：The goal of this research is to understand more about parents’ expectations for their cancer-affected children. Methods: A semi-structured interview with 20 families of cancer children took place in a tertiary, level A general hospital in Xinjiang.To obtain qualitative data, phenomenological research methods were used to examine the parents’ short and long-term planning and expectations. Results: Our findings revealed that the expectations of parents of children with cancer may be divided into two broad periods. 1) As part of a short-term strategy. Expectations for children’s physical and mental health,as well as education and the hope that children would be able to adjust to social situations, were at the top of the list. 2) Parents’ long-term expectations were lower in terms of academic success and career planning, but they were more concerned about their children’s marriages and the possibility of kids. Conclusion： Parents were perplexed about their children’s future path choices when they were diagnosed with cancer, and there was a significant difference between anticipation and reality. According to our findings, medical practitioners should make the barriers and tensions faced by children’s families clearer, aid parents and give social support and compassionate care to children’s families.

Metastatic laryngeal cancers are rare and usually indicate advanced disease once they are present; we described a case of a 60 years old male patient with stage IV colorectal cancer (CRC) who presented to our clinic with dysphonia; further workups showed metastatic CRC.

Prenatal diagnosis of hypoplastic aortic arch and coarctation of aorta is still challenging and remains one of the most difficult cardiac defect to diagnose. The results reveal significant improvement of prenatal diagnosis of hypoplastic arch and coactation of aorta. The data also shows the significant overlapping of fetal aortic isthmus z score between the infants who need the arch procedure and those who do not.