Miracle-dz/UniFAR-FTUs huggingface dataset:
Engineered Cerebral Organoids Recapitulate Adult Tau Expression and Disease-relevant Changes in Tau Splicing

The tauopathies are a collection of clinically and pathologically diverse neurodegenerative disorders characterised by tau pathology. The tau protein exists as multiple protein isoforms in the adult human CNS, generated by alternative splicing of the MAPT gene. Disruptions to tau splicing are associated with a number of tauopathies, however, in vitro and in vivo models to understand the consequences of disrupted tau splicing have been lacking, due in part to species differences in tau splicing and the developmental regulation of tau in human neurons. We investigated the utility of iPSC-derived cerebral organoids to model key aspects of tau biology. Cerebral organoids showed high variability in neuronal content and tau expression. To reduce this heterogeneity, we generated engineered cerebral organoids (enCORs), which use a floating scaffold to increase the efficiency of neural induction and reduce heterogeneity. We show that enCORs provide a robust and reproducible in vitro system for the analysis of tau expression and splicing in a 3D model. To investigate the effect of tau mutations, we generated enCORs from an isogenic series of iPSC with the MAPT 10+16 and P301S mutations. The presence of tau splicing mutations results in disease-associated alterations in tau expression, specifically a dose-dependent increase in 4R tau isoforms in the presence of the MAPT 10+16 variant. While the developmental regulation of tau splicing is conserved, maturation of tau splicing is accelerated in 3D cultures compared to 2D cultures. Finally, enCORs with coding mutations in MAPT are able to produce seed-competent tau species, suggesting enCORs recapitulate early features of tau pathology. In summary, enCORs provide a novel, robust in vitro system for the study of tau in development and disease.
Changes in Oral Mucosa during Pregnancy

The main aim of this review is to understand the changes in oral mucosa during pregnancy. This review highlights the major oral complication during pregnancy. Changes in the gingiva and physiological structure of the tooth take place in addition to hormonal, immunologic, dietary and behavioural changes. Characteristics of pregnancy gingivitis are that it gets swollen, smooth and tends to bleed easily. Enlargement of gingiva may occur but it tends to resolves within few months after delivery. Due to the increase in salivary microorganisms, there may be a decrease in salivary pH and impairment of buffer effect. This may also lead to dental caries or erosion during lactation period. The dental management of pregnant patients requires special attention. Dentists, for example, may delay certain elective procedures so that they coincide with the periods of pregnancy which are devoted to maturation versus organogenesis. At other times, the dental care professionals need to alter their normal pharmacological armamentarium to address the patients’ needs versus the foetal demands. Applying the basics of preventive dentistry at the primary level will broaden the scope of the prenatal care. Dentists should encourage all the patients of the childbearing ages to seek oral health counselling and examinations as soon as they learn that they are pregnant
TO COMPARE MANUKA HONEY DRESSING WITH CONVENTIONAL DRESSING IN SURGICAL WOUND

Surgical wounds can cause painful lengthy hospital stay, multiple stages of surgeries, prolonged disability, prolonged rehabilitation, loss of income and enormous financial burden. Manuka honey has high level of non-peroxide anti-bacterial and anti-inflammatory activity which makes it highly suitable for topical use in the treatment of wounds. Manuka honey is gathered in New Zealand from the manuka bush, Leptospermum scoparium, which grows uncultivated throughout the country. Aim of the study is to compare the efficacy of manuka honey dressing and conventional dressing on surgical wounds. This study was carried out in the Department of Surgery, Krishna Institute of Medical Sciences, Karad. Data was collected from 100 patients with surgical wounds admitted in the hospital during the period from May 2013 to April 2014 for this study considering the inclusion and exclusion criteria. In our study we found that manuka honey dressing lead to faster healing of wounds as compared to that of conventional dressing. In case of superficial burn wound, disrupted abdominal wound following caesarean section, chronic leg ulcer, diabetic foot healing was faster as compared to conventional method but in Fournier gangrene healing was delayed with manuka honey. Results are formulated and conclusion of my study is that there was large body of evidence to support the use of honey as a wound dressing for a wide range of types of wound. Its antibacterial activity rapidly clears infection and protects wounds from becoming infected, thus it provides a moist healing environment.
Controllable Dual Skew Divergence Loss for Neural Machine Translation.

In sequence prediction tasks like neural machine translation, training with cross-entropy loss often leads to models that overgeneralize and plunge into local optima. In this paper, we propose an extended loss function called \emph{dual skew divergence} (DSD) that integrates two symmetric terms on KL divergences with a balanced weight. We empirically discovered that such a balanced weight plays a crucial role in applying the proposed DSD loss into deep models. Thus we eventually develop a controllable DSD loss for general-purpose scenarios. Our experiments indicate that switching to the DSD loss after the convergence of ML training helps models escape local optima and stimulates stable performance improvements. Our evaluations on the WMT 2014 English-German and English-French translation tasks demonstrate that the proposed loss as a general and convenient mean for NMT training indeed brings performance improvement in comparison to strong baselines.
The Opportunity Cost of Hedging under Incomplete Information: Evidence from ETF/Ns

This paper considers the optimal hedge ratio problem under estimation risk. Due to incomplete information, the decision-maker evaluates the opportunity cost of hedging using exchange-traded funds or notes (ETF/Ns). Using a back-testing procedure over the last five years and 13 different hedging instruments - both inverse-equity ETFs and volatility ETNs - we quantify the proposed opportunity cost using different out-of-sample performance metrics. Given the greater accessibility of commission-free brokers for small investors along with the popularity of ETF/Ns, our paper appeals to retail investors and provides guidance in terms of choosing the optimal hedge ratio under estimation risk.
Traditional Herbal Remedies used for the Treatment of Diabetes in South Eastern Region of Nepal

Traditional knowledge has become recognized worldwide to control many diseases and diabetes is also one of them. In Nepal, remote areas are the root of the indigenous knowledge of medicinal plants. The present study aimed to record traditional medicinal uses of plants to control diabetes. Several times interactions were done with the traditional healers, local knowledgeable old person and other informants like few local people and household visits. A total of 39 plant species of 35 genera belonging to 23 angiosperm families were found to be used in diabetes. About 36 types of herbal remedies were investigated from the rural inhabitants of the area. These traditional recipes include extracts, leaves, powders, flour, seeds, vegetables, fruits and herbal mixtures. Traditional knowledge systems are culturally valued and scientifically important. Strengthening and disseminating the use -value of these plants can save the money and life of poor people.
Association between lung injury and cytokine profile in COVID-19 pneumonia

Background: Coronavirus disease 2019 (COVID-19) is a systemic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The purpose of the present study was to investigate the association between lung injury and cytokine profile in COVID-19 pneumonia.Methods: This retrospective study was conducted in COVID-19 patients. Demographic characteristics, symptoms, signs, underlying diseases, and laboratory data were collected. The patients were divided into COVID-19 with pneumonia and without pneumonia. CT severity score and PaO2/FiO2 ratio and were used to assess lung injury.Results: 106 patients with 12 COVID-19 without pneumonia and 94 COVID-19 with pneumonia were included. Compared with COVID-19 without pneumonia, COVID-19 with pneumonia had significant higher serum interleukin (IL)-2R, IL-6, and tumor necrosis factor (TNF)-α. Correlation analysis showed that CT severity score and PaO2/FiO2 were significantly correlated with age, presence of any coexisting disorder, lymphocyte count, procalcitonin, IL-2R, and IL-6. In multivariate analysis, log IL6 was only independent explanatory variables for CT severity score (β=0.397, p<0.001) and PaO2/FiO2 (β=-0.434, p=0.003). Conclusions: Elevation of circulating cytokines was significantly associated with presence of pneumonia in COVID-19 and the severity of lung injury in COVID-19 pneumonia. Circulating IL-6 independently predicted the severity of lung injury in COVID-19 pneumonia.
Under-reaction: Irrational behavior or robust response to model misspecification?

Under-reaction is a robust response to model misspecification rewarded by financial markets, rather than an “irrational” attitude that leads to extinction. I show that under-reacting rules guarantee predictions as accurate as Bayes’ in well-specified learning problems and beat Bayes’ in many misspecified learning environments. Therefore, when a Bayesian agent trades with an under-reacting agent with the same information, there are no paths on which the under-reacting agent loses all his wealth against the Bayesian, while there is a large class of misspecified learning settings in which the Bayesian agent loses all his wealth against the under-reacting agent.
The effect of the politically connected CEO on credit risk in Iranian commercial banks

It has been widely stated in the theoretical literature that political connections increase the value of organizations. Political connections may have both a positive and negative effect on the performance of the bank. Politically connected banks may have better access to financing, timely liquidity support from the central bank or banks which are connected with other political organizations and reduction in the pressure of legal authorities if such a reduction is possible, such as the easy passage of legal inspection. A politically connected bank can also use communications to exchange assistance to achieve the organization's goals. Therefore, answering the question of whether banks' political connections have a positive or negative impact on their financial performance cannot be answered with certainty. This study attempts to investigate the effects of interactions between politically connected CEO (PCCEO), independent directors, and credit risk of banks in an emerging country context where corporate governance systems appear weak. In this study, to collect the required data, we use the information database of Codal publishers for the listed banks in the Tehran Stock Exchange and the information existing in the performance report of the Iranian banks for public banks that collected by the Iran Banking Institute. For the investigation of this issue, we employ the SGMM method (System Generalized Method of Moments) or in other words, dynamic GMM approach, and we find politically connected boards to exert significant influence on credit risk.
Serial interval of COVID-19 and the effect of Variant B.1.1.7: analyses from a prospective community cohort study (Virus Watch).

Introduction Increased transmissibility of B.1. 17 variant of concern (VOC) in the UK may explain its rapid emergence and global spread. We analysed data from putative household infector infectee pairs in the Virus Watch Community cohort study to assess the serial interval of COVID-19 and whether this was affected by emergence of the B.1. 17 variant. Methods The Virus Watch study is an online, prospective, community cohort study following up entire households in England and Wales during the COVID-19 pandemic. Putative household infector infectee pairs were identified where more than one person in the household had a positive swab matched to an illness episode. Data on whether individual infections were caused by the B.1. 1.7 variant were not available. We therefore developed a classification system based on the percentage of cases estimated to be due to B.1. 17 in national surveillance data for different English regions and study weeks. Results Out of 24,887 illnesses reported, 915 tested positive for SARS-CoV-2 and 186 likely infector infectee pairs in 186 households amongst 372 individuals were identified. The mean COVID-19 serial interval was 3.18 (95%CI: 2.55;3.81) days. There was no significant difference (p=0.267) between the mean serial interval for Variants of Concern (VOC) hotspots (mean = 3.64 days, (95%CI: 2.55;4.73)) days and non-VOC hotspots, (mean = 2.72 days, (95%CI: 1.48;3.96)). Conclusions Our estimates of the average serial interval of COVID-19 are broadly similar to estimates from previous studies and we find no evidence that B.1. 1.7 is associated with a change in serial intervals. Alternative explanations such as increased viral load, longer period of viral shedding or improved receptor binding may instead explain the increased transmissibility and rapid spread and should undergo further investigation.
MiR-139-5p is a causal biomarker for type 2 diabetes; Results from genome-wide microRNA profiling and Mendelian randomization analysis in a population-based study

MicroRNAs (miRNAs) have emerged as key regulators of gene expression. Differential expression of miRNAs has been linked to diabetes, but underlying pathways remain poorly understood. We performed genome-wide miRNAs profiling and tested the causal associations between miRNAs and type 2 diabetes in the general population. Subsequently, we investigated target genes and metabolites of miRNAs to provide insight into the metabolic disturbances that emerge with type 2 diabetes. Between 2002 and 2005, plasma levels of 2083 circulatory miRNAs were profiled in 1900 participants (mean age 71.4 years) of the population-based Rotterdam Study cohort. The associations of 591 well-expressed miRNAs with prevalent and incident type 2 diabetes were examined until 2015. Two-sample Mendelian Randomization (MR) was conducted to investigate the causal associations and miRNA-target genes and metabolites were studied in relation to type 2 diabetes. At baseline, higher plasma levels of miR-139-5p and miR-193a-5p were associated (FDR<0.05) with prevalent type 2 diabetes (n=253 cases). During a follow-up of >9.0 years, 209 participants developed type 2 diabetes. Plasma levels of miR-99a-5p, miR-4664-3p, miR-29a-3p, miR-122-5p, and miR-125b-5p were significantly associated with incident type 2 diabetes (n=209). Two-sample MR confirmed a causal effect for miR-139-5p (MR-IWV-beta=0.10, p=3.51x10-4) on type 2 diabetes. We found several target genes and metabolites that could link miR-139-5p to pathways underlying type 2 diabetes. Our study indicates a causal relationship between miR-139-5p and type 2 diabetes and suggests this miRNA as a plasma biomarker of type 2 diabetes.
REACT-1 round 11 report: low prevalence of SARS-CoV-2 infection in the community prior to the third step of the English roadmap out of lockdown

Background National epidemic dynamics of SARS-CoV-2 infections are being driven by: the degree of recent indoor mixing (both social and workplace), vaccine coverage, intrinsic properties of the circulating lineages, and prior history of infection (via natural immunity). In England, infections, hospitalisations and deaths fell during the first two steps of the 'roadmap' for exiting the third national lockdown. The third step of the roadmap in England takes place on 17 May 2021. Methods We report the most recent findings on community infections from the REal-time Assessment of Community Transmission-1 (REACT-1) study in which a swab is obtained from a representative cross-sectional sample of the population in England and tested using PCR. Round 11 of REACT-1 commenced self-administered swab-collection on 15 April 2021 and completed collections on 3 May 2021. We compare the results of REACT-1 round 11 to round 10, in which swabs were collected from 11 to 30 March 2021. Results Between rounds 10 and 11, prevalence of swab-positivity dropped by 50% in England from 0.20% (0.17%, 0.23%) to 0.10% (0.08%, 0.13%), with a corresponding R estimate of 0.90 (0.87, 0.94). Rates of swab-positivity fell in the 55 to 64 year old group from 0.17% (0.12%, 0.25%) in round 10 to 0.06% (0.04%, 0.11%) in round 11. Prevalence in round 11 was higher in the 25 to 34 year old group at 0.21% (0.12%, 0.38%) than in the 55 to 64 year olds and also higher in participants of Asian ethnicity at 0.31% (0.16%, 0.60%) compared with white participants at 0.09% (0.07%, 0.11%). Based on sequence data for positive samples for which a lineage could be identified, we estimate that 92.3% (75.9%, 97.9%, n=24) of infections were from the B.1. 1.7 lineage compared to 7.7% (2.1%, 24.1%, n=2) from the B.1. 617.2 lineage. Both samples from the B.1. 617.2 lineage were detected in London from participants not reporting travel in the previous two weeks. Also, allowing for suitable lag periods, the prior close alignment between prevalence of infections and hospitalisations and deaths nationally has diverged. Discussion We observed marked reductions in prevalence from March to April and early May 2021 in England reflecting the success of the vaccination programme and despite easing of restrictions during lockdown. However, there is potential upwards pressure on prevalence from the further easing of lockdown regulations and presence of the B.1. 617.2 lineage. If prevalence rises in the coming weeks, policy-makers will need to assess the possible impact on hospitalisations and deaths. In addition, consideration should be given to other health and economic impacts if increased levels of community transmission occur.
PR ] 1 6 A pr 2 02 1 Quadratic variation and quadratic roughness

We study the concept of quadratic variation of a continuous path along a sequence of partitions and its dependence with respect to the choice of the partition sequence. We define the concept of quadratic roughness of a path along a partition sequence and show that, for Hölder-continuous paths satisfying this roughness condition, the quadratic variation along balanced partitions is invariant with respect to the choice of the partition sequence. Typical paths of Brownian motion are shown to satisfy this quadratic roughness property almostsurely along any partition with a required step size condition. Using these results we derive a formulation of Föllmer’s pathwise integration along paths with finite quadratic variation which is invariant with respect to the partition sequence.
Encountered Space and Situated Lay-Knowledge: A Mixed Methods Approach

This research draws on the geographical concept of situated lay-knowledge to highlight how the formation of tourists’ attitudes to travel destinations challenges the theoretical foundation of the theory of planned behavior (TPB). It suggests that situated lay knowledge is dynamic as opposed to static, which is the accepted basis of TPB, and subsequently, proposes a “Situated Lay-Knowledge Travel Behavior Model” (SLKTB). The model was tested in a mixed methods approach where Chinese tourists, who knew little about Portugal, encountered Portuguese culture and cuisine in Macau. The overall results demonstrate that the formation of tourists’ attitudes about travel destinations is not preexisting or static but dynamic and created from their ongoing encounters.
Mechanical phase mapping of the Taza meteorite using correlated high‐speed nanoindentation and EDX

Meteorites have one of the most unique and beautiful microstructures, the Widmanstätten structure. This consists of large, elongated bands which form an intricate octahedral lace of crystalline metal. This structure makes meteorites an ideal case to demonstrate the capabilities of mechanical phase mapping using high‐speed nanoindentation. In this work, the mechanical properties and composition of the Taza meteorite were mapped using ~100,000 indentations to statistically determine the properties of the individual phases. Five microstructural phases were characterized in this meteorite: Kamacite, Plessite, Tetrataenite, Cloudy Zone, and Schreibersite. Mechanical phase identification was confirmed using EDX measurements, and the first direct, point‐to‐point correlation of EDX and large‐scale indentation maps was achieved. Mechanical phase maps showed superior phase contrast to EDX in two phases. An indentation property map or a mechanical phase map using a 2D histogram was used to visualize and statistically characterize the phases and identify trends in their relationships.
Host Range of Cotton Flea Beetle (Podagrica puncticollis) in a Hot Dry Tropical Environment of Ethiopia

Cotton flea beetle, Podagrica puncticollis is the most destructive insect pest of cotton in north-western part of Ethiopia. This study was conducted to identify and determine the host range of cotton flea beetle in Metema area. The field survey was undertaken from June 27, 2015 to January 9, 2016 in ten kebele administrations of the district. At least three fields were prospected after every 15 days, in each kebele for host plants as well as to determine population density and percent leaf damage by adult cotton flea beetle, at different growth stages of cotton plant. The composition of plant species with damaged symptom or infested by flea beetle was analysed using quantitative means and identified by comparing specimens with description of identification manuals. A total of 11 host plant species of cotton flea beetle were identified in the cotton growing areas of Metema throughout a season. Indigofera longibarbata (Fabaceae), Hibiscus articulatus, H. cannabinus, H. vitifolius, Abutilon figarianum, Sida alba and S. urens (Malvaceae), Bidens pilosa and B. setigera (Asteraceae), Corchorus olitorius and C. trilocularis (Tiliaceae) found to be common host plants of cotton flea beetle. Thus, among the host plants, H. vitifolius, H. cannabinus, H. articulatus, C. olitorius and C. trilocularis were the most suitable hosts for adult cotton flea beetle in respect of the number of adults per plant and percent foliage damage they sustained. These findings could aid in developing longterm management strategies for this important insect pest existing in a hot dry tropical environment of north-western Ethiopia.
Monetary Policy and Intangible Investment

We contrast how monetary policy affects intangible relative to tangible investment. We document that the stock prices of firms with more intangible assets react less to monetary policy shocks, as identified from Fed Funds futures movements around FOMC announcements. Consistent with the stock price results, instrumental variable local projections confirm that the total investment in firms with more intangible assets responds less to monetary policy, and that intangible investment responds less to monetary policy compared to tangible investment. We identify two mechanisms behind these results. First, firms with intangible assets use less collateral, and therefore respond less to the credit channel of monetary policy. Second, intangible assets have higher depreciation rates, so interest rate changes affect their user cost of capital relatively less.