Miracle-dz/UniFAR-FTUs huggingface dataset:
A Fluorometric CYP19A1 (Aromatase) Activity Assay in Live Cells

Inhibition of estrogen synthesis is an integral component of the frontline pharmacologic therapy for the treatment of estrogen receptor positive cancers. However, there is currently no direct, high‐throughput‐ready assay for aromatase (also known as CYP19A1) that can be performed in live cells. Herein we present a cell‐based assay that allows for multiplexed assessment of enzyme activity, protein half‐life, cell viability, and identification of inhibitors with slow off‐rates.
Effectiveness of Tinnitan Duo® in Subjective Tinnitus with Emotional Affectation: A Prospective, Interventional Study

Abstract To assess the effectiveness of a food supplement (Tinnitan Duo®) containing 5-hydroxytryptophan, Ginkgo biloba, magnesium, melatonin, vitamin B5 and B6, and zinc at improving tinnitus response and intensity. Prospective, single-center interventional study including patients with subjective tinnitus and emotional affectation. The primary endpoint was the change in the Tinnitus Handicap Inventory (THI) total score and the emotional subscale after 3 months of treatment. Secondary endpoints were the change from baseline to month 3 in (1) the Tinnitus Distress Rating (TDR) scale, and (2) in hearing status, and the safety profile of patients throughout the study. Sixty-one patients were included, and 29 completed the study. The THI total score was significantly reduced after 3 months of treatment in the per-protocol (PP, all the patients with no major protocol deviations) and intention-to-treat (ITT) populations (−15.7 and −7.5, respectively; p = 0.001). The emotional subscale score significantly decreased after 3 months of treatment by −5.6 in the PP (p = 0.001) and by −2.6 in the ITT populations (p = 0.001). Perceived tinnitus loudness significantly decreased after 3 months of treatment (p = 0.001). The audiogram showed no significant changes in hearing status after 3 months of treatment. Of the five adverse events (AEs) reported, all were mild or moderate, and three were related to the study treatment (two headaches and one dizziness). This new food supplement was associated with an improved tinnitus-related emotional affectation and with a good safety profile.
Normative References for Graphomotor and Latency Digital Clock Drawing Metrics for Adults Age 55 and Older: Operationalizing the Production of a Normal Appearing Clock.

BACKGROUND Relative to the abundance of publications on dementia and clock drawing, there is limited literature operationalizing 'normal' clock production. OBJECTIVE To operationalize subtle behavioral patterns seen in normal digital clock drawing to command and copy conditions. METHODS From two research cohorts of cognitively-well participants age 55 plus who completed digital clock drawing to command and copy conditions (n = 430), we examined variables operationalizing clock face construction, digit placement, clock hand construction, and a variety of time-based, latency measures. Data are stratified by age, education, handedness, and number anchoring. RESULTS Normative data are provided in supplementary tables. Typical errors reported in clock research with dementia were largely absent. Adults age 55 plus produce symmetric clock faces with one stroke, with minimal overshoot and digit misplacement, and hands with expected hour hand to minute hand ratio. Data suggest digitally acquired graphomotor and latency differences based on handedness, age, education, and anchoring. CONCLUSION Data provide useful benchmarks from which to assess digital clock drawing performance in Alzheimer's disease and related dementias.
Enhanced absorption of surface plasma wave by metal nano-particles in the presence of external magnetic field

The absorption of surface plasma wave (SPW) by metal nanoparticles embedded on the metal surface is studied in the presence of an external magnetic field. As a surface wave of frequency ω ? > propagates through nanoparticles, electrons start oscillating and anomalous absorption of energy takes place at resonance frequency ω≈ωpe/3 ? >, where ωpe ? > is the plasma frequency of electrons inside the nanoparticles. The absorption of the surface plasma wave by the nanoparticles enhances significantly in the presence of a magnetic field at modified resonance frequency ω≈1/2[ωc+ωc2+4ωpe2/3] ? > (where ωc ? > is the cyclotron frequency). The absorption constant is directly proportional to the cube of a nanoparticle radius and inversely proportional to the square of interparticle separation. Maximum absorption constant kip≈0. 85ωpe/c ? > is achieved for gold nanoparticles of the radius rc=20 nm ? > with interparticle separation d=112 nm ? > and normalized cyclotron frequency (ωc/ωpe=0.04) ? >. These results are of direct importance in nanoparticle based magneto-plasma solar cells.
Defect‐Engineered Dzyaloshinskii–Moriya Interaction and Electric‐Field‐Switchable Topological Spin Texture in SrRuO3

In situ electrical control of the Dzyaloshinskii–Moriya interaction (DMI) is one of the central but challenging goals toward skyrmion‐based device applications. An atomic design of defective interfaces in spin–orbit‐coupled transition‐metal oxides can be an appealing strategy to achieve this goal. In this work, by utilizing the distinct formation energies and diffusion barriers of oxygen vacancies at SrRuO3/SrTiO3(001), a sharp interface is constructed between oxygen‐deficient and stoichiometric SrRuO3. This interfacial inversion‐symmetry breaking leads to a sizable DMI, which can induce skyrmionic magnetic bubbles and the topological Hall effect in a more than 10 unit‐cell‐thick SrRuO3. This topological spin texture can be reversibly manipulated through the migration of oxygen vacancies under electric gating. In particular, the topological Hall signal can be deterministically switched ON and OFF. This result implies that the defect‐engineered topological spin textures may offer an alternate perspective for future skyrmion‐based memristor and synaptic devices.
Convergent and Discriminant Validity of Default Mode Network and Limbic Network Perfusion in Amnestic Mild Cognitive Impairment Patients.

BACKGROUND Previous studies reported default mode network (DMN) and limbic network (LIN) brain perfusion deficits in patients with amnestic mild cognitive impairment (aMCI), frequently a prodromal stage of Alzheimer's disease (AD). However, the validity of these measures as AD markers has not yet been tested using MRI arterial spin labeling (ASL). OBJECTIVE To investigate the convergent and discriminant validity of DMN and LIN perfusion in aMCI. METHODS We collected core AD markers (amyloid-β 42 [Aβ 42], phosphorylated tau 181 levels in cerebrospinal fluid [CSF]), neurodegenerative (hippocampal volumes and CSF total tau), vascular (white matter hyperintensities), genetic (apolipoprotein E [APOE] status), and cognitive features (memory functioning on Paired Associate Learning test [PAL]) in 14 aMCI patients. Cerebral blood flow (CBF) was extracted from DMN and LIN using ASL and correlated with AD features to assess convergent validity. Discriminant validity was assessed carrying out the same analysis with AD-unrelated features, i.e., somatomotor and visual networks' perfusion, cerebellar volume, and processing speed. RESULTS Perfusion was reduced in the DMN (F = 5.486, p = 0.039) and LIN (F = 12.678, p = 0.004) in APOE ɛ4 carriers compared to non-carriers. LIN perfusion correlated with CSF Aβ 42 levels (r = 0.678, p = 0.022) and memory impairment (PAL, number of errors, r = -0.779, p = 0.002). No significant correlation was detected with tau, neurodegeneration, and vascular features, nor with AD-unrelated features. CONCLUSION Our results support the validity of DMN and LIN ASL perfusion as AD markers in aMCI, indicating a significant correlation between CBF and amyloidosis, APOE ɛ4, and memory impairment.
Qualitative exploration into reasons for delay in seeking medical help with diabetic foot problems

ABSTRACT Purpose Delay in reporting foot symptoms in patients with diabetes to health-care professionals is said to be responsible for limb amputation. While reasons for these delays have been investigated elsewhere, they are not well documented in Nigeria. This study explored the causes of delayed presentation in a Nigerian sample of patients with diabetic foot ulcers. Method The study followed an explorative qualitative design in which the lived experience of eight participants with diabetes were explored. The participants completed in-depth interviews which were digitally audio-recorded and transcribed verbatim. Data were analysed thematically using deductive reasoning. Results The study identified four themes which included knowledge and awareness of foot challenges, risk perception, health seeking triggers and behaviours and competing priority as the factors responsible for delay in presentation of diabetic foot complications. Conclusions Limited knowledge and awareness and negative health seeking behaviours including self-management and consultation of traditionalists were the major reasons for delays.
Evaluating collaborative practice within community-based integrated health and social care teams: a systematic review of outcome measurement instruments

ABSTRACT Collaborative practice is a workforce priority for integrated health and social care systems internationally, requiring robust outcome measurement instruments (OMIs) to enable team development and good quality research. In this systematic review, we appraised self-administered OMIs that could be used to measure team-based collaborative practice within integrated health and social care teams in community settings. The most important measurement properties when selecting between OMIs are content and structural validity and internal consistency. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) systematic review method was modified to evaluate each OMI. For each measurement property, the methodological quality of individual studies and quality of each parameter were rated, and the level of evidence graded. A search strategy applied to 19 bibliographic databases identified 7 instruments that met eligibility criteria. A total of 6 development studies, 6 content validity studies, 8 studies for structural validity, and 10 for internal consistency were included. Only the shortened version of the Assessment of Interprofessional Team Collaboration Scale (ATICS-II) was rated as Sufficient for each measurement property with Very Low or Moderate quality evidence. Further validation of each OMI for use by community integrated teams is needed; studies evaluating relevance, comprehensibility and comprehensiveness are a priority.
Exploring the use of the service ecosystem framework to examine how smart city actors co-create value

The world is facing unprecedented levels of urbanization (Dirks & Keeling, 2009). Half of the world population resides in cities, while ten per cent (10%) lives in only 30 metropolis (Dobbs et al., 2011). In 2008, 75% of the European population lived in urban areas, while this percentage is expected to rise to 80% by 2020 (United Nations, 2011). Even though cities occupy less than 2% of the earth’s land, urban inhabitants consume more than 75% of the natural resources available worldwide (Marceau, 2008). Moreover, the urban population is expected to double from 2.6 billion in 2010 to 5.2 billion in 2050 (United Nations, 2011). Cities are already facing numerous challenges that are bound to increase due to rapid urbanization.
Degradation of chitosan for rice crops application

A variety of techniques including chemical and enzymatic hydrolysis, and radiation degradation processes can be used to prepare low molecular weight chitosan. Degradation of chitosan by radiation can be carried out in solid state and liquid state. Radiation degraded polysaccharides has been reported to exhibit growth-stimulating activity like phytohormones thatinduce the promotion in germination, shoot and root elongation in variety of plants. In this study, the chitosan was irradiated in solid state (powder form) by gamma rays within the dose range of 25-75 kGy. And the irradiated chitosan was then irradiated in solution form in the presence of hydrogen peroxide. The effects of irradiation on the molecular weight and viscosity of the chitosan were investigated using Ubbelohde Capillary Viscometer. The molecular weight and viscosity of the chitosan decreased with increment of absorbed doses. In the presence of hydrogen peroxide, the molecular weight of chitosan could be further decreased. The effect of radiation degraded chitosan on the growth promotion of rice was investigated and it was shown during seedling period of 15 days for transplanting whereby the growth is 15%-20% faster than using chemicals growth promoters.
High confidence identification of intra-host single nucleotide variants for person-to-person influenza transmission tracking in congregate settings

Influenza within-host viral populations are the source of all global influenza diversity and play an important role in driving the evolution and escape of the influenza virus from human immune responses, antiviral treatment, and vaccines, and have been used in precision tracking of influenza transmission chains. Next Generation Sequencing (NGS) has greatly improved our ability to study these populations, however, major challenges remain, such as accurate identification of intra-host single nucleotide variants (iSNVs) that represent within-host viral diversity of influenza virus. In order to investigate the sources and the frequency of called iSNVs in influenza samples, we used a set of longitudinal influenza patient samples collected within a University of Maryland (UMD) cohort of college students in a living learning community. Our results indicate that technical replicates aid in removal of random RT-PCR, PCR, and platform sequencing errors, while the use of clonal plasmids for removal of systematic errors is more important in samples of low RNA abundance. We show that the choice of reference for read mapping affects the frequency of called iSNVs, with the sample self-reference resulting in the lowest amount of iSNV noise. The importance of variant caller choice is also highlighted in our study, as we observe differential sensitivity of variant callers to the mapping reference choice, as well as the poor overlap of their called iSNVs. Based on this, we develop an approach for identification of highly probable iSNVs by removal of sequencing and bioinformatics algorithm-associated errors, which we implement in phylogenetic analyses of the UMD samples for a greater resolution of transmission links. In addition to identifying closely related transmission connections supported by the presence of highly confident shared iSNVs between patients, our results also indicate that the rate of minor variant turnover within a host may be a limiting factor for utilization of iSNVs to determine patient epidemiological links.
Why amyloid fibrils have a limited width

Amyloid fibrils can grow indefinitely long by adding protein chains to the tips of the fibril through β-sheet hydrogen bonding; however, they do not grow laterally beyond ∼10-20 nm. This prevents amyloid fibrils from growing into two-dimensional or three-dimensional arrays. The forces that restrict lateral association of β-sheets in amyloid fibrils are not immediately apparent. We hypothesize that it is the helical symmetry of amyloid fibrils that imposes the limit on fibril width by incurring an increasing separation between helically related molecules as a function of radial distance from the helical axis. The unavoidable consequence is that backbone hydrogen bonds that connect symmetrically related layers of the fibril become weaker towards the edge of the fibril, ultimately becoming too weak to remain ordered. To test our hypothesis, we examined 57 available cryo-EM amyloid fibril structures for trends in interstrand distance and β-sheet hydrogen bonding as a function of radial distance from the helical axis. We find that all fibril structures display an increase in interstrand distance as a function of radius and that most fibril structures have a discernible increase in β-sheet hydrogen bond distances as a function of radius. In addition, we identify a high resolution cryo-EM structure that does not follow our predicted hydrogen bonding trends and perform real space refinement with hydrogen bond distance and angle restraints to restore predicted hydrogen bond trends. This highlights the potential to use our analysis to ensure realistic hydrogen bonding in amyloid fibrils when atomic resolution cryo-EM maps are not available. Significance Statement The number of amyloid fibril structures determined has exploded in recent years due to advances in structural biology techniques. However, we are still at the beginning stages of understanding amyloid fibril assembly. One important property that is critical to fibril formation and mechanical properties is the fibril width. Despite the diversity of fibril folds discovered, all amyloid fibrils are constrained to a width of 10-20 nm. Here, we use simple geometry and structural analysis to identify that the limited width of amyloid fibrils arises from the helical twist of β-sheets in amyloid fibrils. Our findings provide important considerations for the accurate modeling of hydrogen bonds in amyloid fibrils as well as for the possible prediction and design of amyloid-based nanomaterials.
Identification of Novel Translated Small Open Reading Frames in Escherichia coli Using Complementary Ribosome Profiling Approaches

Small proteins of <51 amino acids are abundant across all domains of life, but they are often overlooked because their small size makes them difficult to predict computationally and they are refractory to standard proteomic approaches. Recent studies have discovered small proteins by mapping the location of translating ribosomes on RNA using a technique known as ribosome profiling. ABSTRACT Small proteins of <51 amino acids are abundant across all domains of life, but they are often overlooked because their small size makes them difficult to predict computationally and they are refractory to standard proteomic approaches. Ribosome profiling has been used to infer the existence of small proteins by detecting the translation of the corresponding open reading frames (ORFs). Detection of translated short ORFs by ribosome profiling can be improved by treating cells with drugs that stall ribosomes at specific codons. Here, we combine the analysis of ribosome profiling data for Escherichia coli cells treated with antibiotics that stall ribosomes at either the start or stop codons. Thus, we identify ribosome-occupied start and stop codons with high sensitivity for ∼400 novel putative ORFs. The newly discovered ORFs are mostly short, with 365 encoding proteins of <51 amino acids. We validate translation of several selected short ORFs and show that many likely encode unstable proteins. Moreover, we present evidence that most of the newly identified short ORFs are not under purifying selection, suggesting that they do not impact cell fitness, although a small subset have the hallmarks of functional ORFs. IMPORTANCE Small proteins of <51 amino acids are abundant across all domains of life, but they are often overlooked because their small size makes them difficult to predict computationally and they are refractory to standard proteomic approaches. Recent studies have discovered small proteins by mapping the location of translating ribosomes on RNA using a technique known as ribosome profiling. Discovery of translated sORFs using ribosome profiling can be improved by treating cells with drugs that trap initiating ribosomes. Here, we show that combining these data with equivalent data for cells treated with a drug that stalls terminating ribosomes facilitates the discovery of small proteins. We use this approach to discover 365 putative genes that encode small proteins in Escherichia coli.
Knowledge-based antibody repertoire simulation, a novel allele detection tool evaluation and application

Detailed knowledge of the diverse immunoglobulin germline genes is critical for the study of humoral immunity. Hundreds of alleles have been discovered by analyzing antibody repertoire sequencing (Rep-seq or Ig-seq) data via multiple novel allele detection tools (NADTs). However, the performance of these NADTs through antibody sequences with intrinsic somatic hypermutations (SHMs) is unclear. Here, we developed a tool to simulate repertoires by integrating the full spectrum features of an antibody repertoire such as germline gene usage, junctional modification, position-specific SHM and clonal expansion based on 2152 high-quality datasets. We then systematically evaluated these NADTs using both simulated and genuine Ig-seq datasets. Finally, we applied these NADTs to 687 Ig-seq datasets and identified 43 novel alleles using defined criteria. Twenty-five alleles were validated through findings of other sources. In addition to the novel alleles detected, our simulation tool, the results of our comparison, and the streamline of this process may benefit further humoral immunity studies via Ig-seq.
A topographical and physiological exploration of C-tactile afferents and their response to menthol and histamine

Numerous microneurography studies in the human peroneal nerve have suggested that CT afferents are lacking in the more distal parts of the limbs. Here we recorded from unmyelinated low-threshold mechanosensitive afferents in the peroneal and radial nerves, with the most distal receptive fields located on the proximal phalanx of the third finger for the superficial branch of the radial nerve, and near the lateral malleolus for the peroneal nerve. We found that the physiological properties with regard to conduction velocity and mechanical threshold, as well as their tuning to brush velocity, were similar in CT units across the antebrachial, radial and peroneal nerves. Moreover, we found that while CT afferents are readily found during microneurography of the arm nerves, they appear to be much more sparse in the lower leg compared to C nociceptors. We continued to explore CT afferents with regard to their chemical sensitivity and found that they could not be activated by topical application to their receptive field of either the cooling agent menthol or the pruritogen histamine. In light of previous studies showing the combined effects that temperature and mechanical stimuli have on these neurons, including a lack of responsiveness to heat, these findings add to the growing body of research suggesting that CT afferents constitute a unique class of sensory afferents with highly specialized mechanisms for transducing gentle touch.
Broad-scale variation in human genetic diversity levels is predicted by purifying selection on coding and non-coding elements

Analyses of genetic variation in many taxa have established that neutral genetic diversity is shaped by natural selection at linked sites. Whether the mode of selection is primarily the fixation of strongly beneficial alleles (selective sweeps) or purifying selection on deleterious mutations (background selection) remains unknown, however. We address this question in humans by fitting a model of the joint effects of selective sweeps and background selection to autosomal polymorphism data from the 1000 Genomes Project. After controlling for variation in mutation rates along the genome, a model of background selection alone explains ∼60% of the variance in diversity levels at the megabase scale. Adding the effects of selective sweeps driven by adaptive substitutions to the model does not improve the fit, and when both modes of selection are considered jointly, selective sweeps are estimated to have had little or no effect on linked neutral diversity. The regions under purifying selection are best predicted by phylogenetic conservation, with ∼80% of the deleterious mutations affecting neutral diversity occurring in non-exonic regions. Thus, background selection is the dominant mode of linked selection in humans, with marked effects on diversity levels throughout autosomes.