Targeted sequencing is an increasingly popular Next Generation Sequencing (NGS) approach for studying populations, through focusing sequencing efforts on specific parts of the genome of a species of interest. Methodologies and tools for designing targeted baits are scarce but in high demand. Here, we present specific guidelines and considerations for designing capture sequencing experiments for population genetics for both neutral genomic regions and regions subject to selection. We describe the bait design process for three diverse fish species: Atlantic salmon, Atlantic cod and tiger shark, which was carried out in our research group, and provide an evaluation of the performance of our approach across both historical and modern samples. The workflow used for designing these three bait sets has been implemented in the R-package supeRbaits, which encompass our considerations and guidelines for bait design to benefit researchers and practitioners. The supeRbaits R package is user‐friendly and versatile. It is written in C++ and implemented in R. supeRbaits and its manual are available from Github: https://github.com/BelenJM/supeRbaits

The multidimentional human rights catastrophe 2020-2021 is input for this writing. We see it as the culmination of arguments about regulating the social values, the right to freedom of thought, conscience and religion in Europe (art 9 ECHR) in its broader sense. We question: what are thought, conscience, religion in Europe? The paper aims at revealing how different states bound by ECHR (Italy, France, Russia) are redefining their relationship to thought, conscience and religion, under the challenge of changing minds, increasing religious activism in the public sphere, associated with the spread of new religious movements and Islam; how this process mobilizes a complex array of often unrelated official actors, but also mindful men who want to be recognized by public opinion eager to curb what is perceived as "foreign" or "extremist" expressions of thought, conscience, religion; by politicians navigating between political correctness and populism, by national and external judiciary like ECtHR; how this process is gradually producing a new and common paradigm of the relationship between states, the public sphere and thought, conscience and religion. We scrutinize (re)construction and formatting of thought, conscience and religion in the West through courts, giving the rebirthing to the Lautsi case. We intend to find which doctrine\idea has been developed by the Court in Europe. What will be with judicial decision-making in France and Europe? How to overcome the crisis? We are seeking a new instrument. We go into Mindful Politics/Judiciary, Dharma and Judiciary/Politics. We use the Complex Thinking concept and Quantum Theory, Sophism, Theology, Eastern and Ancient thoughts as Puzzles. We refer to Lady Justice-Prudentia-Sophia and Phronesis. We refer to the decoloniality to re-learn the thoughts-heritage that have been pushed aside, buried, discredited by the forces of modernity: UN Secretary-General Dag Hammarskjold, Vl.Solovjev, Ivan Ilyin. Also we use new data, such as O'Murchu Diarmuid, Doing Theology in an Evolutionary Way (2021), Rovelli Carlo, Helgoland (2020), Molari Carlo, Il cammino spirituale del cristiano (2020), Mancuso Vito, I quattro maestri (2020). Our core topic is the importance of legal ideas and legal doctrine for court decisions. Our core thought is the Russia's experience in balancing secular and religious values and peaceful coexistence of peoples, it's importantance for the international community. It's part of the big research, started in 1990, continued in different ways, at UNIPV (with Prof.J.Ziller) in the framework of CICOPS, in particular. Key terms: human rights and freedom, thought, conscience, religion, pluralism, equality, secularism, neutrality, positivism, legal symbols, Lady Justice, Sophia, Prudentia, Phronesis, quantum theory, Islam, rule of law, legitimacy, historical-interpretive account of judicial politics, complexity.

A rigorous mathematical model was developed for a complex liquid-liquid-solid system in a batch reactor. The approach is general but particularly well applicable for the indirect epoxidation of vegetable oils according to the concept of N. Prileschajew. The model considers intra- and interfacial mass transfer effects coupled to the reaction kinetics. The liquid phases were described with chemical approach (aqueous phase) and a reaction-diffusion approach (oil phase). The oil droplets were treated as rigid spheres, in which the overall reaction rate is influenced by chemical reactions and molecular diffusion phenomena. The model was tested with a generic example, where two reactions proceeded simultaneously in the aqueous and oil phases. The example (i.e. fatty acid epoxidation à la Prileschajew) illustrated the power of the real multiphase model in epoxidation processes. The proposed modelling concept can be used for optimization purposes for many applications, which comprise a complex water-oil-solid catalyst system.

High heat duty is an urgent challenge for industrial applications of amine-based CO2 capture. In this work, we report a novel, stable, efficient, and inexpensive Ni-HZSM-5 catalyst to reduce the heat duty. The density functional theory (DFT) calculations successfully explain the catalytic performance. The catalytic activity associates with the combined properties of MSA × B/L × Ni2+. The 7.85-Ni-HZ catalyst presents an excellent catalytic activity for the CO2 desorption: it increases the amount of desorbed CO2 up to 36%, reduces the heat duty by 27.07% compared with the blank run, and possesses high stability during five cyclic tests. A possible catalytic mechanism for the Ni-HZSM-5 catalysts through assisting carbamate breakdown and promoting CO2 desorption is proposed based on experimental results and theoretical calculations. Therefore, the results present that the 7.85-Ni-HZ catalyst significantly accelerates the protons transfer in CO2 desorption and can potentially apply in industrial CO2 capture.

A CFD model for oxygen permeation and partial oxidation of methane (POM) to syngas in a La0.6Sr0.4Co0.2Fe0.8O3-δ tubular membrane reactor was adopted to investigate the effects of the methane space velocity (MSV) and the feed composition on the reactor performance. It is shown that coupling POM reaction with carbon dioxide and steam reforming of methane (CRM and SRM), which is realized by co-feeding CH4 with CO2, H2O or CO2-H2O mixture into the reactor, can significantly enhance the methane conversion and syngas production rate and alter the H2/CO ratio as compared with feeding CH4 alone. For co-feeding CH4 with CO2, H2O or CO2-H2O mixture, the maximum syngas production rate is 2.3, 2 and 1.8 times that of feeding CH4 alone. Also, when POM is coupled with CRM and SRM, the temperature inside the reactor can be maintained above 973 K which is required for proper functioning of the membrane and catalyst.

This study presents the chromatographic purification of immunoglobulin G (IgG) from human plasma using a two-column process integrating the peptide-based adsorbents LigaGuardTM, which captures non-Ig plasma proteins in flow-through mode, and LigaTrapTM, which isolates IgG in bind-and-elute. Buffer composition and column loading were optimized for both adsorbents. Two process configurations were evaluated. In the first design, plasma was fed to a LigaGuardTM column to capture plasma proteins, the effluent was loaded on the LigaTrapTM column, and the bound IgG was eluted with 63.8% global recovery and 99.7% purity; in comparison, Protein G agarose afforded ~67% recovery and 97.2% purity. In the alternative design, the LigaGuardTM column was utilized to polish the LigaTrapTM elution stream, affording 82.3% global recovery and 98.8% purity. Collectively, these results demonstrate the potential of a fully chromatographic process for purifying polyclonal IgG from plasma feedstocks.

Background: The goal of mucoactive therapies in cystic fibrosis (CF) is to enhance sputum clearance and to reduce a progressive decline in lung function over the patient’s lifetime. We aimed to investigate the level of consensus among specialists from Italian CF Centers on appropriateness of therapeutic use of dornase alfa (rhDNase) for CF patients. Method: A consensus on appropriate prescribing in CF mucoactive agents was appraised by an online Delphi method, based on a panel of 27 pulmonologists, coordinated by a Scientific Committee of six experts in medical care of patients with CF. Results: Full or very high consensus was reached on several issues related to therapeutic use of dornase alfa for CF patients in clinical practice. Conclusions: Modified Delphi method was used to define the most appropriate use of dornase alfa in routine CF to improve lung function and long-term outcomes in patients, in agreement with international guidelines on CF management.

Title: Activation Pattern During His-Bundle PacingOmar Yasin MD, MS1, Jamie Bush BS2, Vaibhav Vaidya MBBS1, Jason Tri1, Martin van Zyl, MBBCh1, Peilin Xiao PhD3, Jie Han MD, PhD4, Cory Scheuermann3, Samuel J. Asirvatham, MD1,5, Yong-Mei Cha, M.D1Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USABoston Scientific Corporation, Washington DC, USAThe Second Affiliated Hospital of Chongqing Medical University, Chongqing ChinaThe First Affiliated Hospital of Zhejiang University, Hangzhou, ChinaDepartment of Pediatrics and Adolescent Medicine, Mayo clinic, Rochester, MN, USAFunding: NoneDisclosures: NoneCorresponding AuthorYong-Mei Cha, MD, FHRSDepartment of Cardiovascular Diseases, Mayo Clinic200 1st ST SWRochester, MN 55901Email:ycha@mayo.edu

Cell-released nanovesicles can induce anti-leukemia immunity. Leukemia cell-derived exosomes (LEXs) are promising anti-tumor vaccine components for cancer immunotherapy. Nonetheless, LEX-based vaccines show modest potency in vivo, likely due to the presence of immunosuppressive PD-L1 proteins in the exosomes. We hypothesized that targeting exosomal PD-L1 could optimize LEX-based vaccines. To test this hypothesis, we compared the capacity of exosomes derived from PD-L1-silenced leukemia cells (LEXPD-L1si) and non-modified exosomes to induce anti-leukemia immunity.Lentivirus-mediated PD-L1 shRNA was used to downregulate PD-L1 expression in parental leukemia cells and LEXs. LEXPD-L1si were characterized by electron microscopy, western blotting, and flow cytometry, and their anti-leukemia immune effects were tested on immune cells and in animal models.In the present study, lentivirus-mediated PD-L1 shRNA successfully downregulated PD-L1 expression in parental leukemia cells and in LEXs. LEXPD-L1si induced better DC maturation and subsequently enhanced T-cell activation, as compared with non-modified LEXs. Consistently, immunization with LEXPD-L1si induced greater T-cell proliferation and Th1 cytokine release. LEXPD-L1si was a more potent inducer of antigen-specific cytotoxic lymphocyte (CTL) response. Finally, we vaccinated DBA/2 mice with exosome formulations to test their ability to induce both protective and therapeutic anti-tumor CTL responses in vivo. Vaccination with LEXPD-L1si strongly inhibited tumor growth and prolonged survival. Downregulation of exosomal PD-L1 expression in LEXs effectively induce more potent anti-leukemia immunity. Therefore our strategy for optimizing LEX-based vaccine has a potential application in leukemia immunotherapy.

We describe a 74-year-old female who presented with thrombocytopenia 20 days after receiving her first dose of the novel mRNA vaccine. After an exhaustive workup, Immune Thrombocytopenia was diagnosed secondary to her recent mRNA vaccine administration. She was treated aggressively with high-dose steroids and IVIG, with adequate response.

Of the 1061 patients of coronavirus disease-2019 admitted to our field hospital, eight patients (0.75%) had pneumothorax. The mean age of incidence was 79.9 years; six of these patients (75%) died. Although pneumothorax is a rare complication of coronavirus disease-2019, it suggests a poor prognosis in elderly patients.

Identification of phenotypic characteristics in reproductively successful individuals provides important insights into the evolutionary processes that cause range shifts due to environmental change. Female beluga whales (Delphinapterus leucas) from the Baffin Bay region (BB) of the Canadian Arctic in the core area of the species’ geographic range have larger body size than their conspecifics at the southern range periphery in Hudson Bay (HB). We investigated the mechanism for this north and south divergence as it relates to ovarian reproductive activity (ORA = total corpora) that combines morphometric data with ovarian corpora counted from female reproductive tracts. Based on the previous finding of reproductive senescence in older HB females, but not for BB whales, we compared ORA patterns of the two populations with age and body length. Female beluga whale ORA increased more quickly with age (63% partial variation explained) in BB than in HB (41%). In contrast, body length in HB female beluga whales accounted for considerably more of the total variation (12 vs 1%) in ORA compared to BB whales. We speculate that female HB beluga whale ORA was more strongly linked with body length due to higher population density resulting in food competition that favors the energetic advantages of larger body size during seasonal food limitations. Understanding the evolutionary mechanism of how ORA varies across a species’ range will assist conservation efforts in anticipating and mitigating future challenges associated with a warming planet.

Introduction: Free-of-charge (FoC) medicine schemes are increasingly available and allow access to investigational treatments outside clinical trials or in advance of licensing or NHS commissioning. Methods: We retrospectively reviewed FoC medicine schemes evaluated between 2013 and 2019 by a single NHS trust and a regional drug and therapeutics committee (DTC). The details of each locally reviewed FoC scheme, and any nationally available MHRA Early Access to Medicines Scheme (MHRA EAMS) in the same period, were recorded and categorised. Results: Most FoC schemes (95%) allowed access to medicines intended to address an unmet clinical need. Over 7 years, 90% were company-FoC schemes and 10% were MHRA EAMS that were locally reviewed. Phase 3 clinical trial data were available for 44% of FoC schemes; 37% had phase 2 data; and 19% were supported only by phase 1, retrospective observational studies, or pre-clinical data. Utilisation of company-FoC schemes increased on average by 50% per year, while MHRA EAMS showed little growth. Conclusion: Company-FoC medicine schemes are increasingly common. This may indicate a preference for pharmaceutical companies to independently co-ordinate schemes. Motivations for company-FoC schemes remain unclear and many provide access to treatments that are yet to be evaluated in appropriately conducted clinical trials, and whose efficacy and risk of harm remain uncertain. There is no standardisation of this practice and there is no regulatory oversight. Moreover, no standardised data collection framework is in place that could demonstrate the utility of such programmes in addressing unmet clinical need or allow generation of further evidence.

The low activity of dihydroxy-acid dehydratase (DHAD) on dehydration of glycerate to pyruvate hampers its applications in the biosystems. Protein engineering of a thermophilic DHAD from Sulfolobus solfataricus (SsDHAD) was performed to increase its dehydratation activity. A novel high-throughput method was established. A triple-mutant (I161M/Y145S/G205K) with a 10-fold higher activity on glycerate dehydration was obtained after three rounds of iterative saturation mutagenesis (ISM) based on computational analysis. The shrunk substrate-binding pocket and newly formed hydrogen bonds were the reason for the activity improvement of the mutant. For the in vitro synthetic enzymatic biosystems of converting glucose or glycerol to L-lactate, the biosystems with the mutant SsDHAD showed 3.32- and 2.34-times of the reaction rate than that of wild type, respectively. This study demonstrates the potential of protein engineering to improve the efficiency of in vitro synthetic enzymatic biosystems by enhancing the enzyme activity of rate-limited enzymes.

Left hepatic vein draining into coronary sinus is a rare systemic vascular anomaly. Its presence is significant when it is associated with other cardiac lesions requiring surgery. We report technical challenges in a case of persistent left superior vena cava and left hepatic vein draining into coronary sinus in an adult with ostium secundum atrial septal defect, which was repaired through minimally invasive approach. Main technical challenge in this case was to achieve adequate venous drainage, which was achieved by vacuum assistance and by manipulating the position of femoral venous cannula. We approached through right anterolateral thoracotomy, adequate venous drainage was achieved without cannulating left hepatic vein or left superior vena cav.

A document by J. Kevin Yin. Click on the document to view its contents.

Background Little is known regarding the impact of right ventricular (RV) function on clinical outcomes following MitraClip therapy. Objectives The aim of this study was to investigate the prognostic impact of RV dysfunction and its cut-off value following MitraClip therapy. Methods Consecutive 77 patients (median 79 years, 33% female) who underwent MitraClip therapy were enrolled. Clinical endpoint was defined as cardiovascular (CV) events, including cardiovascular death and rehospitalization for heart failure (HF). Results and conclusions Twenty-two (29%) patients had primary mitral regurgitation (MR). During follow-up, 5 patients died due to CV events, 8 were hospitalized for HF. On univariate Cox regression analysis, CV events were associated with eGFR (HR; 0.960, 95% CI; 0.926–0.995, p = 0.027), tricuspid annular plane systolic excursion (TAPSE, HR; 0.874, 95% CI; 0.789–0.968, p = 0.010), and significant residual MR (HR; 11.652, 95% CI; 3.257–41.691, p <0.001). On multivariate Cox regression analysis, TAPSE (HR; 0.788, 95% CI; 0.788–0.987, p = 0.029) and significant residual MR (HR; 9.373, 95% CI; 2.581–34.033, p = 0.001) were independently associated with CV events. TAPSE <11 mm was the best cut-off criteria for predicting CV events. RV function was independently associated with clinical outcomes following MitraClip therapy. TAPSE is a simple parameter for predicting CV events in patients with MR who are undergoing MitraClip therapy.

COVID-19 Virus has affected the world in many ways, resulting in several challenges. COVID 19 vaccines were introduced recently, with a variable degree of immunogenicity and safety. We report a 61-year-old man who had GBS a few days after Receiving The vaccine, his condition improved after 5 days of IVIG

Objectives: Left ventricular assist device (LVAD) implantation is a common therapy for end-stage heart failure. LVAD patients often present with atrial fibrillation (AF). The purpose of this study was to evaluate the influence of AF in combination with vascular complications on outcome in LVAD patients. Methods: Between 01/2010 and 12/2017, 168 patients (141 male) with end-stage heart failure underwent LVAD implantation at a single center. Patient outcome was retrospectively studied using the Kaplan-Meier method for analyzing crude survival as well as Cox regression for analyzing risk factors. Results: Sixty-two patients suffered from preoperative atrial fibrillation at LVAD implantation. Mean age was 56.8±11.9 years (range: 22–79) and 141 (84%) were male. Postoperatively, vascular or visceral surgical management due to malperfusion was needed in 27 patients (16.1%) and did not correlate with postoperative mortality (p=0.121, HR=1.587, CI=0.885–2.845). Patient with AF had by trend an impaired outcome in Kaplan-Meier analysis (p=0.069). Cox regression analysis revealed postoperative AF (n=53, p=0.316, HR=1.281, CI=0.789–2.079), preoperative mechanical support (MCS) [extracorporeal membrane oxygenator (ECMO), intraaortic balloon pump, Abiomed Impella® (n=74, p=0.160, HR=1.391, CI=0.878-2.206)] as no significant risk factors for death. Conclusions: Our data suggest preoperative AF may be a potential predictor of mortality and impaired long-term outcome in LVAD patients. In contrast preoperative ECLS and vascular or visceral surgery after LVAD implantation did not represent limiting factors with regard to mortality after LVAD implantation.

Present-day ecology and population structure are the legacies of past climate and habitat perturbations, and this is particularly true for species that are widely distributed at high latitudes. The red knot, Calidris canutus, is an arctic-breeding, long-distance migratory shorebird with six recognized subspecies defined by differences in morphology, migration behavior, and annual-cycle phenology, in a global distribution thought to have arisen just since the Last Glacial Maximum (LGM). We used nextRAD sequencing of 10,881 single-nucleotide polymorphisms (SNPs) to assess the neutral genetic structure and phylogeographic history of 172 red knots representing all known global breeding populations. Using population genetics approaches, including model-based scenario-testing in an approximate Bayesian computation (ABC) framework, we infer that red knots derive from two main lineages that diverged ca. 34,000 years ago, and thus persisted at the LGM in both Palearctic and Nearctic refugia, followed by at least two instances of secondary contact and admixture. In two flyways, we detected clear genetic structure between population pairs with similar migrations and substantial geographic overlap in the non-breeding season. Conversely, other populations were only weakly differentiated despite clearly divergent migratory phenotypes and little or no apparent contact throughout the annual cycle. In general, the magnitude of genetic differentiation did not match that of phenotypic differences among populations, suggesting that flyway-specific phenotypes developed quite rapidly and do not necessarily impose barriers to gene flow. Our results suggest that population structure and migratory phenotypes in red knots arose from a complex interplay among phylogeography, plasticity, and selective processes.

Electricity is an important part of our daily life and uses for different purposes. However, electricity generation sources are decreasing day by day and electricity mainly generates from renewable and conventional sources of energy. Proper management to create new conventional energy sources is challenging all over the world. Lack of conventional sources of energy, high demand for energy, less available land, and low budget for energy are some of the important factors that cause poor energy management all over the world. In this paper, different potential less attributed sources of energy are analyzed along with their implementation techniques to mitigate high electricity demand in near-future. This review shows that along with renewable and conventional sources of energy, less attended energy sources would be a potential source that can generate electricity. This review also presents that no improved techniques are needed to implement less attended sources of energy and can be implemented with sustainable techniques. This study also proposes implementation techniques of uncommon sources of energy for electricity generation with related challenges that could emerge during the implementation of these sources of energy. In this study, the electricity generation rate and their corresponding applications are also depicted. Proper steps and execution of less attended sources of energy would mitigate high energy demand all over the world and offers a cleaner environment for livelihood.

We hereby present a case report of an extremely preterm newborn with bronchopulmonary dysplasia (BPD), spending more than 4 months of his early life in the newborn intensive care unit (NICU). The uniqueness of this case report is the difference in the algorithm used for the treatment of BPD with regards to the family’s preference and its successful outcome.

G-type immunoglobulins (IgGs) are extensively used in the pharmaceutical industry against various diseases, being also crucial in multiple immunoassays. The production of secondary monoclonal antibodies (Abs) for IgG detection is not cost-effective, while polyclonal antibody production still depends on laboratory animals, which raises concerns regarding animal welfare. As alternatives, bacterial proteins (A and G) have been widely exploited; however, several difficulties are encountered regarding their use for IgG detection and purification. The widespread use of IgGs in the pharmaceutical industry and the increasing number and variety of new Abs entering the market impose the need to develop new detection and purification strategies. The TRIM21 protein is a soluble intracellular IgG receptor that binds to the Fc region of many species with high affinity. We created a chimeric protein containing a mutated form of the C-terminal domain of mouse TRIM21 linked to a streptavidin moiety to detect IgGs from a wide range of species. The protein is promptly produced by heterologous expression and consists of an improved molecular tool, expanding the portfolio of Ab-affinity ligands for immunoassays.

The incidence of postoperative recurrent coarctation of the aorta ranges from 5% to 50%, and largely depends on the age at initial repair. Due to the increased fibrosity and rigidity of the aorta in older age, stent placement is preferred instead of balloon angioplasty, resulting in an almost complete relief of the gradient in >95% of the patients. In patients with transverse arch hypoplasia, transcatheter intervention with further surgical intervention may be needed, and the use of stenting was shown to be effective in the treatment of patients with hypoplastic isthmus, arch or tubular coarctation. In this case of a late re-coarctation, we preferred to apply a hybrid technique for treatment. The first step of the treatment was debranching of the brachiocephalic and left common carotid arteries with upper mini median sternotomy. On the following day, the patient underwent a successful stent placement to the transvers arch.