This work concerns the typical conformational behaviors for di-substituted cyclohexanes that inherently depend on spatial orientations of side chains in flexible cyclic ring. The 1,3-dimethylcyclohexane and 1,4-dimethylcyclohexane in both cis- and trans-configurations were focused here to unravel their conformational inversion-topomerization mechanisms. Full geometry optimizations were performed at B3LYP/6-311++G(d,p) level of theory to explicitly identify all distinguishable molecular structures, and thus explore potential energy surfaces (PES) of the complete interconversion routes for two stereoisomers of 1,3-dimethylcyclohexane and 1,4-dimethylcyclohexane. Additional quantum calculations were carried out by separately applying MP2/6-311++G(d,p), G4, and CCSD(T)/6-311++G(d,p) methods to further refine all PES’ stationary points. With respect to quantum results, the conformational analysis was conducted to gain insight into the determination, thermodynamic stabilities, and relative energies of distinct molecular geometric structures. On base of highly biased conformational equilibria, the temperature-dependent populations of stable local minima for four studied dimethylcyclohexanes were obtained by utilizing Boltzmann distribution within 300-2500 K. Moreover, two unique interconversion processes for them, including inversion and topomerization, were fully investigated, and their potential energy surfaces were illustrated with the rigorous descriptions in two or three-dimensional schemes for clarify.

Promoting the application potential of graphenes in biomolecule adsorption and detection is of great significance in the field of nanobiotechnology. In this paper, the density functional theory calculation was used to study the adsorption and sensing of L-cysteine on graphene-based compounds, single-vacancy and double-vacancy graphenes (XSV and XDV) doped with 3p-bolck elements (Al, Si, P, and S). Along with the dopant changing from Al to S, XSV exhibits decreasing exothermical chemisorption to endothermical chemi-sorption, while XDV exhibits decreasing exothermical chemisorption to endothermical physisorption. L-cysteine adsorption on XDV is weaker than corresponding adsorption on XSV. Valence electron number, and atomic ionization potential, modulated by the 3p-block dopant, and X-C interaction, modulated by the vacancy type, contribute to adsorption mechanism of L-cysteine on XGs. The study could facilitate applications of Al, Si, P and S doped graphenes in biosensing technology, biomolecule immobilization, bioseparation and other fields.

Aims Serum biomarkers have a potential role in the risk stratification of patients with heart valve disease and may help determine the optimal timing of intervention. Much of the published literature relates to biomarker sampling in a resting state, but the relationship of exercise biomarkers is less well described. We performed a systematic review to examine the significance of exercise natriuretic peptides on echocardiographic variables and cardiovascular events, in valvular heart disease. Methods A search for studies that assessed exercise biomarkers in patients with moderate to severe valve lesions was performed. We examined the relationship between rest and exercise BNP and also the endpoints of symptoms, haemodynamic or echocardiographic variables and clinical outcomes. Results 11 prospective studies were identified (844 participants). 61% were male and the mean age was 55.2 ± 9.6 years. The majority of the blood samples were taken at baseline and within 3 minutes of stopping exercise. There was a significant increase in exercise BNP compared with rest, in patients with aortic stenosis, mitral regurgitation and mitral stenosis. Elevated exercise BNP levels correlated with mean gradient and left atrial area, and there was a relationship between a higher exercise BNP and a blunted blood pressure response, in aortic stenosis. Furthermore, exercise BNP was independently associated with cardiac events, over and above resting values, in patients with mitral regurgitation and aortic stenosis. Conclusions The results suggesting that exercise natriuretic peptide levels may have additive prognostic importance over resting levels, as well as demographic and echocardiographic data.

Soil degradation imposes significant environmental and economic impacts on the pastures of drylands worldwide, making livestock grazing systems often unsustainable under the present climate conditions. In this study, we aimed to compare the attributes of the soil of different grazing areas (pastures) using sensitive indicators of changes in the management of these areas, such as the physical-hydric properties and the CO2 efflux (ECO2) from the soil. The study was carried out in three areas of exclosure grazing, understood by three land uses: a pasture of sabi grass (LU1), a silvopastoral system with sabi grass and tree legume (LU2), and an area with sabi grass and a herbaceous native legume (LU3). The measurements were undertaken over nine months and then grouped into three seasons (dry, transition, and rainy). The ECO2 and the ten indicators of soil physical-hydric quality were measured: macroporosity, aeration capacity, plant-available water capacity (PAWC), relative field capacity (RFC), characteristic pore radius, quantity of hydraulically active pores, sorptivity, saturated hydraulic conductivity, soil density, and soil resistance to penetration. The soils in the LU1 and LU3 areas showed limited plant available water capacity (0.10 PAWC < 0.15 cm3 cm-3) and was soil water-limited (RFC < 0.6). The advantages of using silvopastoral systems in semi-arid environments for environmental sustainability are not limited to improvements in the properties of soils, as these areas are also important carbon sinks.

A 39 years old healthy cardiologist with history of two months applying of topical Minoxidil for androgenic alopecia was presented with metamorphopsia and central scotoma. After full medical work-up, CSC was diagnosed. Minoxidil may be the culprit for CSC.

We present a patient with 3 separate primary cancers over the course of 11 years: Follicular Lymphoma, Abdominal mesothelioma and Rectal Adenocarcinoma respectively Multiple primary malignancies are exceedingly rare but they may occur sequentially in a patient. Peritoneal mesothelioma known as a fatal malignancy may completely regress with chemotherapy.

The clinical presentation of cardiac sarcoidosis is variable. We report two cases of cardiac sarcoidosis to highlight the varied clinical presentations and diagnostic challenges in our setting and encourage the consideration of sarcoidosis as a differential in unexplained arrhythmias and heart failure.

The gill tissue of bivalve mollusks hosts rich symbiotic microbial communities that may contribute to the host wellbeing. Spondylus spinosus is a Lessepsian invasive oyster to the eastern Mediterranean Sea that has become highly abundant, while constantly expending its range northwestward. Using 16S rRNA gene amplicon sequencing we examined how temperature affects the gill microbiota of S. spinosus, and the oysters themselves, in a series of experiments: exposing the oysters to the current annual seawater temperature range; to the colder temperature of the western Mediterranean Sea; and to elevated temperature as predicted under global warming scenarios. The bacterial genus Endozoicomonas dominated the communities of the S. spinosus, mainly upon exposure to winter-like temperatures. Exposure to elevated seawater temperature resulted in a significant change in the bacterial communities, while the oysters maintained normal functioning, suggesting that the oyster may survive a seawater warming scenario. Exposure to colder winter temperature typical to the western Mediterranean Sea resulted in health deterioration of the oysters, emergence of opportunistic pathogens, and a decline in the relative abundance of Endozoicomonas, suggesting that S. spinosus might not survive in the cold western Mediterranean Sea. The findings indicate that gill bacteria are greatly affected by temperature, which could consequently restrict the range expansion of this and other invasive oysters.

Background: Cardiac surgery (CS) may be associated with several organic repercussions responsible for the appearance of cardiac risk factors during the postoperative period. These, associated with prolonged hospital length of stay (LoS), may trigger critical manifestations in individuals undergoing this surgical procedure. To investigate the relationships between postoperative cardiac risk factors, LoS, and changes in functioning state. Methods: Patients undergoing reconstructive, substitutive, or corrective cardiac surgeries were evaluated. The presence of postoperative cardiovascular risks was assessed using the InsCor score, while LoS and functionality were collected from medical records. Results: One-hundred patients with a mean age of 59.2±12.3 years were included. Significant correlations between functionality and both the hospital and Intensive Care Unit (ICU) LoS (p<0.0001, ρ= 0.56; p=0.002, ρ=0.29, respectively), as well as between hospital LoS and the number of comorbidities (p=0.003, ρ=0.28) were found. No significant relationships were observed between the number of postoperative risk factors and LoS. Conclusions: Functionality and comorbidities are associated with increased hospital and ICU LoS in patients undergoing cardiac surgery.

Alzheimer’s disease (AD) is a complex neurodegenerative disease in the elderly. It is the most common cause of dementia in human. AD is characterized by accumulation of abnormal protein aggregates including amyloid plaques (composed of beta-amyloid (Aβ) peptides) and neurofibrillary tangles (formed by hyper-phosphorylated tau protein). Besides, synaptic plasticity, neuroinflammation, calcium signaling etc. are found to be dysfunctional as well in AD patients. Autophagy is an evolutionarily conserved lysosome-dependent cellular event in eukaryotes. It is closely linked to the modulation of protein metabolism, through which damaged organelles and mis-folded proteins are degraded and then recycled to maintain protein homeostasis. Accumulating evidence has showed that impaired autophagy contributes to AD pathogenesis. In the present review, we highlight the role of autophagy, including bulk and selective autophagy, in regulating metabolic circuits in AD pathogenesis. We also discuss the potential and future perspectives of autophagy-inducing strategy in AD therapeutics.

The concept of migration means that people are permanently moved from one country or region to another country or region, individually or in groups. So this is a permanent session change. The relocation can take place within the country or abroad, but the important point is that permanent migration in the context of political and economic relations rather than the proximity of the migration distance is important. In this respect, domestic immigration is a major humanitarian, economic and sociocultural problem that needs to be explored and solved. Today, one of the most important themes of many developed western countries is to ensure that the immigrant population and the indigenous people live together in harmony. This is called integration. As a result of living together, concepts such as multiculturalism and dual citizenship have emerged. Migrants, migrants, and children of immigrants appear to be mobile, multi-lingual individuals who are shuttling between receiving and receiving countries. The immigrant and refugee issues are undoubtedly one of the most important securities and survival problems of the time frame we live in. Because what could be more truthful and pathetic than the drama experienced by people who had to leave their country in mass, how and how this desperation can be described. In this study, the relationship between the concept of global citizenship and immigration will be revealed by qualitative research methods. In this context, the phenomenon of global citizenship will be handled from an axiological perspective in the axis of the concept of immigration, acculturation, and globalization.

In this article we report a case of SCC in an untreated 45-year-old male patient of psoriasis. The patient referred to the dermatology department manifesting erythrodermic psoriasis. After taking multiple biopsies from scalp lesions, the result was reported to be SCC with sebaceous differentiation.

Bariatric or weight-loss surgery is a popular option for weight reduction. Depending on the surgical procedure, gastric changes like decreased transit time and volume and increased pH, decreased absorption surface in the small intestine, decreased exposure to bile acids and enterohepatic circulation, and decreased gastrointestinal transit time may be expected. In the years after bariatric surgery, patients will also substantially lose weight. As a result of these changes, the absorption, distribution, metabolism, and/or elimination of drugs may be altered. The purpose of this article is to report the general influence of bariatric surgery on oral drug absorption, and to provide guidance for dosing of commonly used or high-risk drugs in this special population. Upon oral drug administration, the time to maximum concentration is often earlier and this concentration may be higher with less consistent effects on trough concentrations and exposure. Additionally, prescription of liquid formulations to bariatric patients is supported by some reports, even though the high sugar load of these suspensions may be of concern. Studies on extended release medications result in an unaltered exposure for a substantial number of drugs. Also, studies evaluating the influence of timing after surgery show dynamic absorption profiles. Although for this group a specific advice can be proposed for many drugs, we conclude that there is insufficient evidence for general advices for oral drug therapy after bariatric surgery implying that a risk assessment on a case-by-case basis is required for each drug.

Aptamer is short sequence of synthetic oligonucleotides which bind to their cognate target specifically while maintaining similar or higher sensitivity as antibody. Small size, chemical synthesis, low batch variation, cost effectiveness, long shelf life and above all low immunogenicity provide advantages over antibody. The in-vitro selection of aptamer applying a conjoining approach of chemistry and molecular biology is referred as Systematic Evolution of Ligands by Exponential enrichment (SELEX). These initial products of SELEX are considered as first generation aptamers, further modified chemically in an attempt to make it stable in biofluid avoiding nuclease digestion and renal clearance. These types of aptamers are called second generation aptamers. While modification is incorporated, enough care should be taken to maintain its sensitivity and specificity. These modifications and several improvisations have widened the window frame of aptamer application that is currently not only restricted to in-vitro system, but have been used in molecular imaging for disease pathology and treatment. In food industry it is used as sensor for detection of different diseases or fungal infections. In this review we have discussed a brief history of its journey, process of synthesis, different types of modifications to improve its characters. We have also focused on its applications and highlighted its role as therapeutic plus diagnostic; theranostic tools. Finally, the review is concluded with a brief discussion on future prospective in immunotherapy, as well as in identification of novel biomarkers in stem cell, and also in single cell proteomics (scProteomics) to study intra or intertumor heterogeneity at protein level.

Myeloid Leukemia with Down Syndrome (ML-DS) is a unique entity of AML with superior treatment response and overall survival compared to children with AML. Despite all of it, ML-DS survival rates for children in low- and middle-income countries (LMICs) remain poor. We described three ML-DS cases, which were treated with vincristine, cytarabine and daunorubicin plus triple intrathecal drugs. All of our three patients successfully finished the treatment, with two patients were still complete remission until now, and one died two days after finishing the chemotherapy. ML-DS is treatable in our limited-resources setting in Manado, Indonesia.

Objective: to examine the effect of changing levels of support (NAVA-level) during neurally adjusted ventilatory assist (NAVA) in preterm infant with respiratory distress syndrome (RDS) on electrical diaphragm activity. Methods: we included preterm infants admitted to the NICU, who were clinically stable and supported with NAVA, either via an endotracheal tube or via a nasal interface. Patients were recruited in the first 24 hours after the start of NAVA. Following a predefined titration protocol, NAVA levels were progressively increased starting from a level of 0,5 cmH2O/µV and with increments of 0,5 cmH2O/µV every 3 minutes, up to a maximum level of 4,0 cmH2O/µV. Respiratory and ventilation parameters were continuously recorded. Results: Ten patients were studied on NIV-NAVA and three on invasive NAVA. The NIV-NAVA patients had an average gestational age at birth of 31,4 + 3,2 weeks and an average birth weight of 1615 + 609 g. For all patients a breakpoint could be identified during the titration study. The breakpoint was on average at a level of 2,35 + 0,63 cmH2O/µV in the NIV-NAVA group. With increasing NAVA levels, the respiratory rate decreased significantly. For the other parameters no clear trend was observed. No severe complications occurred. Conclusion: Preterm neonates with RDS supported with NAVA display a typical biphasic response to changing NAVA-levels with an identifiable breakpoint. This breakpoint was at a higher NAVA-level than commonly used in this clinical situation, suggesting that higher levels might be needed to optimally support preterm neonates with RDS.

The impact of treatment on the risk of lymphoma in patients with rheumatoid arthritis (RA) is unclear. Here, we aimed to assess if the risk of lymphoma differs according to the type of Tumor Necrosis factor inhibitor (TNFi), comparing monoclonal anti-TNF antibodies (Ab) to the soluble TNF receptor. We used BAFF-transgenic (Tg) mice as a model of autoimmunity-associated lymphoma. Six-month aged BAFF-Tg mice were treated with TNFi for 12 months. Histological examination of the spleen, assessment of the cellular composition of the spleen by flow cytometry and assessment of B cell clonality were performed at sacrifice. Crude mortality and incidence of lymphoma were significantly higher in mice treated with monoclonal anti-TNF Ab compared to both controls and mice treated with the soluble TNF receptor, even at high dose. Flow cytometry analysis revealed decreased splenic macrophage infiltration in mice treated with monoclonal anti-TNF Ab. Overall, this study demonstrates, for the first time, that a very prolonged treatment with monoclonal anti-TNF Ab increase the risk of lymphoma in B cell-driven autoimmunity. This data suggests a closer monitoring for lymphoma development in patients suffering from B cell-driven autoimmune disease with long-term exposure to monoclonal anti-TNF Ab.

In biodiversity conservation, the “SL > SS principle” that a single (or few) large habitat patches (SL) conserve more species than several small patches (SS) is used to prioritize protection of large patches while down-weighting small ones. However, empirical support for this principle is lacking; most studies find SS > SL. We propose a research agenda to resolve this dilemma by asking, “are there consistent, empirically-demonstrated conditions leading to SL > SS?” We develop a hypothesis to answer this question, the “SLOSS cube hypothesis,” which predicts SL > SS only when all three of the following are true: between-patch movement is low, population dynamics are not influenced by spreading-of-risk, and large-scale across-habitat heterogeneity is low. We then propose methods to test this prediction. Many tests are needed, comparing gamma diversity across multiple landscapes varying in number and sizes of patches. If the prediction is not generally supported across tests, then either the mechanisms leading to SL > SS are extremely rare in nature, or they are outweighed by countervailing mechanisms leading to SS > SL (e.g. lower competition or higher immigration in SS), or both. In that case, the SL > SS principle should be abandoned.

The Fontan operation has improved the survival of children born with single ventricle physiology. Selecting candidates for the Fontan operation may be difficult on borderline cases. No clear criterion has been established on the risk for staged Fontan palliation. Another aspect that remains controversial is the indications for fenestration. Intraoperative pulmonary flow study may identify high-risk patients for the procedure. In this report, the authors describe their results with Fontan procedures in children with pulmonary pressure >15 mmHg.

Closure of muscular ventricular septal defects remains a challenge for cardiac surgeons and interventional cardiologists. Different techniques, approaches, and devices are available to increase the success of these procedures. Changwe et al, in this issue of the Journal, describe a novel approach with the usage of a probe-guided system, with encouraging results.

The consideration of realistic load assumptions is important for the fatigue design of highly stressed nodular cast iron components for wind energy application. Especially in case of overloads causing elastic-plastic deformation, residual stresses may have a strong impact on fatigue life. In strain-controlled fatigue tests with constant and variable amplitudes, the influence of overloads on the lifetime was investigated. The overload was applied with the objective to create high tensile residual stresses. During fatigue testing the transient material behavior, cyclic hardening, cyclic relaxation of the residual stresses as well as quasi static creep effects, of the EN-GJS-400-18-LT was recorded and evaluated. To quantify the influence of the transient material behavior on the calculated lifetime, fatigue analyses are carried out with the strain-life approach, both with and without consideration of the transient material behavior. The results show that conservative damage sums are derived if the transient material behavior, especially the relaxation of tensile residual stresses, is neglected.

The COVID-19 pandemic poses a serious threat to global health, and one of the key epidemiological factors that shape the transmission of COVID-19 is its serial interval (SI). Although SI is commonly considered following a probability distribution at a population scale, slight discrepancies in SI across different transmission generations are observed from the aggregated statistics in recent studies. To explore the change in SI across transmission generations, we develop a likelihood-based statistical inference framework to examine and quantify the change in SI. The COVID-19 contact tracing surveillance data in Hong Kong are used for exemplification. We find that the individual SI of COVID-19 is likely to shrink with a rate of 0.72 per generation and 95%CI: (0.54, 0.96) as the transmission generation increases. We speculate that the shrinkage in SI is an outcome of competition among multiple candidate infectors within a cluster of cases. The shrinkage in SI may speed up the transmission process, and thus the nonpharmaceutical interventive strategies are crucially important to mitigate the COVID-19 epidemic.

Surfactant protein C gene (SFTPC) variations may cause hereditary interstitial lung disease (HILD), a disease with variable prognosis. The evaluation of treatment responsiveness of HILD with SFTPC variation remains unclear. We present the case of a child with HILD whose respiratory condition was appropriately evaluated using a high-flow nasal cannula (HFNC). A 12-month-old boy with SFTPC variation developed progressive respiratory failure. Although he was once considered a candidate for lung transplantation, his respiratory condition was improved by hydroxychloroquine treatment, which prevented further therapy. Compared to a conventional nasal cannula, which could not deliver a stable oxygen concentration, HFNC allowed us to evaluate the improvement of oxygenation more accurately.

At least nine felid species can co-occur in Southeast Asia, thus providing an unusual opportunity to investigate poorly known guild structure and the factors controlling it. Using camera-trap data, we quantified space use, temporal activity, and multi-dimensional niche overlap of tiger, clouded leopard, marbled cat, leopard cat, and Asiatic golden cat in Htamanthi Wildlife Sanctuary of Myanmar. We hypothesized that the spatio-temporal behaviour of smaller cats can reflect avoidance of the larger cats, which are both potential competitors and predators, and similar-sized guild members would partition their niches in space or time to reduce competition for resources. Our approach involved single-species occupancy modelling to identify site covariates, pairwise spatial overlap using Bayesian inference, and activity overlap with Kernel density estimation and multivariate analyses to test hypotheses. We found tiger and marbled cats were primarily diurnal, clouded leopard and leopard cat were nocturnal and golden cat exhibited cathemeral activity. We observed a complex pattern of guild assembly and potential competition involving strong niche displacement between the golden cat and marbled cat, but high overlap between the relatively similarly-sized pairing of clouded leopard and golden cat, and the markedly differently-sized tiger -- golden cat pairing. No significant evidence of mesopredator release was observed and the felid assembly in Northern Myanmar appeared to be partitioned mainly on a spatial, rather than temporal, dimension. Nonetheless, the temporal association between the three mesopredators was inversely related to the similarity in their body sizes. The insights into this felid guild revealed that the largest niche differences in the use of space and time occurred between the three smaller species, most evidently between the Asiatic golden cat-marbled cat pairing, followed by marbled cat - leopard cat pairing. This study offers new insight into carnivore guild assembly and, adds substantially to knowledge of five of the least known felids of conservation concern.