Miracle-dz/UniFAR-FTUs huggingface dataset:
Ecological Engineering for the Optimisation of the Land-Based Marine Aquaculture of Coastal Shellfish

Whilst the demand for nutritious and sustainable seafood is increasing, fishing yields are declining due to overfishing and climate change. The inshore aquaculture of marine molluscs—e.g., the suspension-feeding cockle Cerastoderma edule for NW Europe—might be an alternative practice if cost-effective and nature-based technology enhances growth and survival. Our inshore experiments revealed that increasing the seawater residence time resulted in improved water quality. The reduction in sediment loads and stimulation of pelagic microalgal growth resulted in enhanced shell growth and meat content of the wild cockles seeded into the system. Shorter residence times resulted also in an increase in benthic microalgae, but the concurrent increase in silt content of the sediment appeared to hamper effective filtration by cockles. The growth conditions (with respect to the water and sediment quality) for the inshore cultivation of cockles can indeed be improved by means of ecological engineering, suggesting that the inshore aquaculture of marine shellfish can provide sustainable food and income for coastal communities, in particular when the shellfish farms are located in low-lying salinized coastal areas where common agriculture practices are no longer profitable. The involvement of the shellfishery industry was and will be crucial for studying and understanding the complex practice of cockle cultivation.
Multiple sexual partnerships and associated factors among young psychoactive-substance-users in informal settlements in Kampala, Uganda

Background Multiple sexual partnerships increase the risk of transmission of HIV and can be exacerbated by substance abuse. However, the association between psychoactive substance use and multiple sexual partnerships among young people in informal settlements of low-income countries is not well known. This study established the prevalence of multiple sexual partnerships and associated factors among young psychoactive-substance-users in informal settlements in Kampala, Uganda. Methods This was a cross-sectional study involving 744 young (aged 18–24 years), sexually active, psychoactive substance-users selected from 12 of the 57 informal settlements of Kampala City. The prevalence of multiple sexual partnerships and their differential distribution by socio-demographic strata was established. Modified Poisson regression models were run in Stata 14 software to generate prevalence rate ratios for the factors associated with multiple sexual partnerships. Results About 40.6% (37.9% of males and 50.0% of females) had engaged in multiple sexual partnerships in the last 30 days. Engaging in multiple sexual partnerships in the last 30 days was positively associated with being female (PR 1.29, 95% CI: 1.03–1.63); staying in the informal settlement for 6–10 years (PR 1.34, 95% CI: 1.02–1.75) and chewing khat in the last 30 days (PR 1.93, 95% CI: 1.10–3.40). Conclusion Multiple sexual partnerships are highly prevalent among young psychoactive-substance-users, irrespective of the socio-demographic strata. Being female, having lived in the informal settlement for 6–10 years, and chewing khat were significantly associated with having multiple sexual partners in the last 30 days. In tackling this high-risk sexual behaviour, it is recommended that risk-reduction interventions are considered for the different socio-demographic strata identified in this study, i.e. females, those who have lived in the informal settlement for about 6–10 years, and those who chew khat.
Sleep, social behaviour and food consumption of schoolchildren of a large Brazilian city

Abstract Objective: To explore the impact of inadequate sleep and associated factors on the social behaviour and food consumption of children and adolescents. Design: Cross-sectional study. Setting: Sleep information, social behaviour (Strengths and Difficulties Questionnaire), food consumption, demography, nutritional status, lifestyle, and biochemical tests were investigated. Participants: School children in the 4th grade of the municipal school system of a large Brazilian city. Results: Of a total of 797 schoolchildren, 50·9 % were female, with a median age of 9·7 (9·5–10·0) years old and an energy consumption of 7613·6 (5982·7–9766·2) kJ. It was determined that 31·6 % were overweight, and 76·8 % reported insufficient weekly practice of physical activity. A median of 9·6 (8·9–10·5) h of sleep (lower values on weekdays: 9·3 v. 10·5 h, P < 0·001) was recorded. In addition, 27 % of the individuals who experienced inadequate sleep (<9 h) engaged in longer screen time daily (≥2 h/d) (P = 0·05), had an inadequate bedtime (> 22 h) or adequate wake-up time (5–7 h), studied in the morning (P < 0·001) and never took a shower before school (P < 0·001). Of the entire sample, 9·9 % had poor or very poor sleep quality and a greater probability of sleep talking regularly, had difficulty falling asleep, and engaged in inadequate social behaviour while experiencing these conditions compared with those with positive sleep quality. There was no association between sleep and the other variables investigated. Conclusions: Sleep impairment contributed to changes in sleep and social behaviour in schoolchildren. The findings of this study may reinforce the importance of developing actions to promote adequate sleep and a healthy lifestyle at school age.
Feedback control of Wnt signaling based on ultrastable histidine cluster co-aggregation between Naked/NKD and Axin

Feedback control is a universal feature of cell signaling pathways. Naked/NKD is a widely conserved feedback regulator of Wnt signaling which controls animal development and tissue homeostasis. Naked/NKD destabilizes Dishevelled, which assembles Wnt signalosomes to inhibit the β-catenin destruction complex via recruitment of Axin. Here, we discover that the molecular mechanism underlying Naked/NKD function relies on its assembly into ultra-stable decameric core aggregates via its conserved C-terminal histidine cluster (HisC). HisC aggregation is facilitated by Dishevelled and depends on accumulation of Naked/NKD during prolonged Wnt stimulation. Naked/NKD HisC cores co-aggregate with a conserved histidine cluster within Axin, to destabilize it along with Dishevelled, possibly via the autophagy receptor p62, which binds to HisC aggregates. Consistent with this, attenuated Wnt responses are observed in CRISPR-engineered flies and human epithelial cells whose Naked/NKD HisC has been deleted. Thus, HisC aggregation by Naked/NKD provides context-dependent feedback control of prolonged Wnt responses.
Ixazomib as Postinduction Maintenance for Patients With Newly Diagnosed Multiple Myeloma Not Undergoing Autologous Stem Cell Transplantation: The Phase III TOURMALINE-MM4 Trial

PURPOSE Maintenance therapy prolongs progression-free survival (PFS) in patients with newly diagnosed multiple myeloma (NDMM) not undergoing autologous stem cell transplantation (ASCT) but has generally been limited to immunomodulatory agents. Other options that complement the induction regimen with favorable toxicity are needed. PATIENTS AND METHODS The phase III, double-blind, placebo-controlled TOURMALINE-MM4 study randomly assigned (3:2) patients with NDMM not undergoing ASCT who achieved better than or equal to partial response after 6-12 months of standard induction therapy to receive the oral proteasome inhibitor (PI) ixazomib or placebo on days 1, 8, and 15 of 28-day cycles as maintenance for 24 months. The primary endpoint was PFS since time of randomization. RESULTS Patients were randomly assigned to receive ixazomib (n = 425) or placebo (n = 281). TOURMALINE-MM4 met its primary endpoint with a 34.1% reduction in risk of progression or death with ixazomib versus placebo (median PFS since randomization, 17.4 v 9.4 months; hazard ratio [HR], 0.659; 95% CI, 0.542 to 0.801; P < .001; median follow-up, 21.1 months). Ixazomib significantly benefitted patients who achieved complete or very good partial response postinduction (median PFS, 25.6 v 12.9 months; HR, 0.586; P < .001). With ixazomib versus placebo, 36.6% versus 23.2% of patients had grade ≥ 3 treatment-emergent adverse events (TEAEs); 12.9% versus 8.0% discontinued treatment because of TEAEs. Common any-grade TEAEs included nausea (26.8% v 8.0%), vomiting (24.2% v 4.3%), and diarrhea (23.2% v 12.3%). There was no increase in new primary malignancies (5.2% v 6.2%); rates of on-study deaths were 2.6% versus 2.2%. CONCLUSION Ixazomib maintenance prolongs PFS with no unexpected toxicity in patients with NDMM not undergoing ASCT. To our knowledge, this is the first PI demonstrated in a randomized clinical trial to have single-agent efficacy for maintenance and is the first oral PI option in this patient population.
In silico exploration of small-molecule α-helix mimetics as inhibitors of SARS-COV-2 attachment to ACE2

Abstract The novel coronavirus, SARS-CoV-2, has infected more than 10 million people and caused more than 502,539 deaths worldwide as of June 2020. The explosive spread of the virus and the rapid increase in the number of cases require the immediate development of effective therapies and vaccines as well as accurate diagnosis tools. The pathogenesis of the disease is triggered by the entry of SARS-CoV-2 via its spike protein into ACE2-bearing host cells, particularly pneumocytes, resulting in overactivation of the immune system, which attacks the infected cells and damages the lung tissue. The interaction of the SARS-CoV-2 receptor binding domain (RBD) with host cells is primarily mediated by the N-terminal helix of ACE2; thus, inhibition of the spike-ACE2 interaction may be a promising therapeutic strategy for blocking the virus entry into host cells. In this paper, we used an in-silico approach to explore small-molecule α-helix mimetics as inhibitors that may disrupt the attachment of SARS-CoV-2 to ACE2. First, the RBD-ACE2 interface in the 6M0J structure was studied by the MM-GBSA decomposition module of the HawkDock server, which led to the identification of two critical target regions in the RBD. Next, two virtual screening experiments of 7236 α-helix mimetics from ASINEX were conducted on the above regions using the iDock tool, which resulted in 10 candidates with favorable binding affinities. Finally, the stability of RBD complexes with the top-two ranked compounds was further validated by 100 ns of molecular dynamics simulations. Communicated by Ramaswamy H. Sarma
Alcohol consumption, cigarette smoking and cancer of unknown primary risk: Results from the Netherlands Cohort Study

Cancer of unknown primary (CUP) is a metastasised malignancy with no identifiable primary tumour origin. Despite the frequent occurrence and bleak prognosis of CUP, research into its aetiology is scarce. Our study investigates alcohol consumption, tobacco smoking and CUP risk. We used data from the Netherlands Cohort Study, a cohort that includes 120 852 participants aged 55 to 69 years, who completed a self‐administered questionnaire on cancer risk factors at baseline. Cancer follow‐up was established through record linkage to the Netherlands Cancer Registry and Dutch Pathology Registry. After 20.3 years of follow‐up, 963 CUP cases and 4288 subcohort members were available for case‐cohort analyses. Multivariable‐adjusted hazard ratios (HRs) were calculated using proportional hazard models. In general, CUP risk increased with higher levels of alcohol intake (Ptrend = .02). The association was more pronounced in participants who drank ≥30 g of ethanol per day (HR: 1.57, 95% confidence interval [CI]: 1.20‐2.05) compared to abstainers. Current smokers were at an increased CUP risk (HR: 1.59, 95% CI: 1.29‐1.97) compared to never smokers. We observed that the more the cigarettes or the longer a participant smoked, the higher the CUP risk was (Ptrend = .003 and Ptrend = .02, respectively). Interaction on additive scale was found for participants with the highest exposure categories of alcohol consumption and cigarette smoking frequency and CUP risk. Our findings demonstrate that alcohol consumption and cigarette smoking are associated with increased CUP risk. Lifestyle recommendations for cancer prevention regarding not drinking alcohol and avoiding exposure to smoking are therefore also valid for CUP.
Catalytic Decarboxylative C-N Formation to Generate Alkyl, Alkenyl and Aryl Amines.

Transition-metal catalyzed sp 2 carbon-nitrogen (C-N) formation is a reliable method with which to synthesize aryl amines. Catalytic sp 3 C-N formation reactions have been reported occasionally, and methods which can realize both sp 2 and sp 3 C-N formation are relatively unexplored. Here we address this challenge with a method of catalytic decarboxylative C-N formation which proceeds through a cascade carboxylic acid activation, acyl azide formation, Curtius rearrangement and nucleophilic addition reaction. The reaction uses naturally abundant organic carboxylic acids as carbon sources, readily prepared azidoformates as the nitrogen sources, and 4-dimethylaminopyridine (DMAP) and Cu(OAc) 2 as catalysts with as low as 0.1 mol% loading, providing protected alkyl, alkenyl and aryl amines in high yields with gaseous N 2 and CO 2 as the only byproducts. Examples are demonstrated of late-stage functionalization of natural products and drug molecules, stereospecific synthesis of useful α-chiral alkyl amines, and rapid construction of different ureas and primary amines.
EVALUATION OF POTATO PEEL EXTRACT AS A SOURCE OF ANTIOXIDANT AND ANTIMICROBIAL SUBSTANCES

Antioxidant and antimicrobial substances were extracted from potato peels by using different solvents (water and both methanol and ethanol at a concentration of 80 and 100 %). The potato peel extracts were evaluated for yield extract, antioxidants activity, total phenols and total flavonoids. The best extracts were selected for their efficacy as an antioxidant and antimicrobial. The proximate composition of dried potato peels indicated that total carbohydrates (65.47 %) were the major compound, while total lipids (2.60 %) were the minor compound. Potato peel methanol extract at concentration 80 % (PPME) had higher yield extract (10.42 %), total phenols (3.78 mg GAE g-1 DW), total flavonoids (0.13 mg Rutine g-1 DW) and antioxidants activity (80.86 %) than other solvent extracts. The vanillic (176.64 µg/ l) and hesperdin (6058.52 µg/ l) were the most abundant phenolic and flavonoid compounds, respectively in PPME. Induction period (using Rancimat instrument) was increased from 5.95 hr for sunflower oil free from PPME to 10. 9 and 11 hr for sunflower oil containing 200 and 400 ppm of PPME, respectively, comparing with 14 hr for sunflower oil containing 200 ppm of butyl hydroxyl toluene (BHT). PPME at 400 ppm was more effective in inhibiting of both gram-positive and gram-negative bacteria and C. albicans than ampicillin.
Genetic Variation Putatively Associated with Mycobacterium tuberculosis Resistance to Perchlozone, a New Thiosemicarbazone: Clues from Whole Genome Sequencing and Implications for Treatment of Multidrug-Resistant Tuberculosis

Perchlozone ([PCZ] 4-thioureido-iminomethylpyridinium perchlorate) is a new thiosemicarbazone approved for the treatment of multidrug-resistant tuberculosis (MDR-TB) in Russia and some other countries. The ethA and hadABC mutations may confer PCZ resistance. At the same time, ethA mutations are known to mediate resistance to ethionamide (ETH) and prothionamide (PTH). We aimed to study the genetic variation underlying Mycobacterium tuberculosis resistance to PCZ through whole genome sequencing (WGS) of consecutive isolates recovered during long-term treatment. This prospective study included patients admitted in 2018–2019 to the regional tuberculosis dispensary, Kaliningrad, Russia, whose treatment regimen included PCZ. Multiple M. tuberculosis isolates were recovered during PCZ treatment, and the bacterial DNA was subjected to WGS followed by bioinformatics analysis. We identified mutations in the genes putatively associated with PCZ resistance, ethA, and hadA. The most frequent one was a frameshift ethA 106 GA > G (seven of nine patients) and most of the other mutations were also likely present before PCZ treatment. In one patient, a frameshift mutation ethA 702 CT > C emerged after six months of PCZ treatment. A frequent presence of cross-resistance mutations to PCZ and ETH/PTH should be taken into consideration when PCZ is included in the treatment regimen of MDR-TB patients.
EVOLUTIONARY AFFINITIES OF TWO RARE LIZARDS FROM NORTHERN URUGUAY

Two lizard species that occur in northern Uruguay are poorly known: Stenocercus azureus and Hemidactylus mabouia. We sequenced the genes 12S and ND2 and estimated phylogenetic trees. The H. mabouia sequence found in Rivera City was unique and more closely related to a widely distributed haplotype found in Brazil, Argentina, and the Caribbean. The S. azureus from near Masoller (Salto) grouped with a sample of S. azureus from Bajada de Pena (Rivera). We encourage further sampling in order to assess the population structure of H. mabouia in Rivera City and to delineate potential conservation units of S. azureus in the region.
Habitat use of Himalayan grey goral in relation to livestock grazing in Machiara National Park, Pakistan

Abstract The Himalayan grey goral (Naemorhedus goral bedfordi) occurs in Pakistan and India, and is classified as Near Threatened on The IUCN Red List. This subspecies is threatened primarily by illegal hunting and competition with livestock, resulting in small and fragmented populations. The present study provides information on habitat use by grey goral at two locations in Machiara National Park (MNP), Azad Jammu and Kashmir, Pakistan, from 2012 to 2013. One location had low grazing pressure from livestock (Machiara), whereas the other had intensive livestock grazing (Serli Sacha). We determined the distribution of grey goral through direct observations of the animals and by the presence of their faecal pellets. We assessed habitat preferences using Ivlev’s electivity index (IEI) by comparing vegetation and topography at used and unused quadrats along nine monitoring lines. Grey gorals strongly avoided areas with high livestock numbers, particularly grazers (cattle Bos taurus and sheep Ovis aries). Grey gorals were most commonly observed on south-facing slopes between 1970 and 2900 m a.s. l. during all seasons. Grey gorals preferred herbs and grasses (IEI=0.14), used shrubby vegetation in proportion to its availability (IEI=0.03), and avoided densely treed areas (IEI=-0.54). Our study suggests that a comprehensive livestock grazing strategy needs to be developed for the conservation of habitat suitable for grey goral in MNP.
Comparison of Climate Model Simulations of the Younger Dryas Cold Event

Results of five climate model simulation studies on the Younger Dryas cold event (YD) are compared with a focus on temperature and precipitation. Relative to the Bolling-Allerod interstadial (BA), the simulations show consistent annual cooling in Europe, Greenland, Alaska, North Africa and over the North Atlantic Ocean and Nordic Seas with maximum reduction of temperatures being simulated over the oceans, ranging from −25 °C to −6 °C. Warmer conditions were simulated in the interior of North America. In two experiments, the mid-to-high latitudes of the Southern Hemisphere were also warmer, associated with a strong bi-polar seesaw mechanism in response to a collapse of the Atlantic meridional overturning circulation (AMOC). The modelled YD-BA temperature response was in general agreement with proxy-based evidence. The simulations reveal reduced YD-BA precipitation (up to 150 mm yr−1) over all regions with major cooling, and over the northern equatorial region. South of the equator, modelled precipitation seemed to increase due to a southward shift of the InterTropical Convergence Zone (ITCZ). The largest uncertainty in the YD is the high-latitude response, where the models show diverging results. This disagreement is partly related to uncertainties in the freshwater forcing. Most model studies assume an AMOC shutdown, but this is incompatible with proxy evidence.
Shocks and Exchange Rates in Small Open Economies*

We separately identify domestic and external shocks in small open economies, and find that they give rise to markedly different exchange rate dynamics. External shocks feature large and predictable deviations from uncovered interest parity, while domestic shocks do not. Moreover, external shocks are associated with fluctuations in global risk aversion and U.S. macroeconomic aggregates. A small open economy model with imperfect capital markets is consistent with these facts. In the model, global risk aversion shocks drive exchange rate dynamics, and a country’s net foreign asset position governs their international transmission. We provide empirical evidence that a country’s exposure to external shocks indeed depends on its net foreign asset position. JEL classification: F31; F41; F44; G15
Bidding Wars for Houses

This paper employs data from the National Association of Realtors to analyze the time series and cross sectional patterns of bidding wars for houses. The paper generates a number of novel stylized facts. Bidding wars – where multiple buyers compete for a house and push its sales price above list price – were once rare, a fairly constant 3-4% of housing sales. This led to treating the list price as a ceiling in empirical and theoretical research on housing transactions. The paper shows that bidding wars have become much more common during the recent housing boom, more than tripling as a share of housing sales between 1995-2005. The share of sales involving bidding wars has fallen during the subsequent bust, but it remains approximately twice as high as it was before the boom. Overall, the paper shows the incidence of bidding wars to be higher in circumstances associated with general macroeconomic and specific housing booms. However, bidding war frequency varies considerably by city, with the share in some cities rising to more than 30% during the boom and the share in other cities rising hardly at all. This variation, and also the rarity of bidding wars during past booms, suggests that the recent growth of bidding wars is not simply a boom phenomenon. The paper also considers – at the MSA and individual housing transaction levels – other potential contributing factors, including buyer irrationality, the use of the internet in home purchases, and land use regulation.
Communication competence and the intensity of anxiety and stress in medical staff – a preliminary report

Summary Communication competencies are crucial in healthcare. Medical staff is exposed to increased emotional stress. It is still unclear, whether the level of communication competencies correlates with stress associated with professional work in healthcare providers. The aim of this study was to determine this relationship and in-vestigate the models of coping with stress among different professional groups in the hospital wards. Methods: The study involved interviewing medical personnel (N=93, 69 female, doctors, nurses, psychologists) to collect the psychological parameters including stress, anxiety, coping strategies and communication skills. Results: Nurses use less often task oriented coping with stress than doctors, while psychologists have higher level of avoidance-oriented style than doctors and nurses. Important associations between readiness for cooperation and the stress levels in doctors (positive) and psychologists (negative) were detected. The level of communication barriers correlated strongly negatively with the level of stress in psychologists. There are important relationships between cooperation and stress levels, individual communication style and anxiety levels. Conclusions: Healthcare professionals use various coping strategies when exposed to stressful situations which depend partly on their profession. The coping strategies used correlate with the communication strategies. Moreover, the level of anxiety is associated with communication competence.