Miracle-dz/UniFAR-FTUs huggingface dataset:
Benchmarking One-Phase Lipid Extractions for Plasma Lipidomics

A key element of successful lipidomics analysis is a sufficient extraction of lipid molecules typically by two-phase systems such as chloroform-based Bligh and Dyer (B&D). However, numerous metabolomics and lipidomics studies today apply easy to use one-phase extractions. In this work, quantitative flow injection analysis high-resolution mass spectrometry was applied to benchmark the lipid recovery of popular one-phase extraction methods for human plasma samples. The following organic solvents were investigated: methanol (MeOH), ethanol (EtOH), 2-propanol (IPA), 1-butanol (BuOH), acetonitrile (ACN) and the solvent mixtures BuOH/MeOH (3:1) and MeOH/ACN (1:1). The recovery of polar lysophospholipids was sufficient for all tested solvents. However, nonpolar lipid classes such as triglycerides (TG) and cholesteryl esters (CE) revealed extraction efficiencies less than 5% due to precipitation in polar solvents EtOH, MeOH, MeOH/ACN, and ACN. Sample pellets also contained a substantial amount of phospholipids, for example, more than 75% of total phosphatidylcholine and sphingomyelin for ACN. The loss of lipids by precipitation was directly related to the polarity of solvents and lipid classes. Although, lipid recovery increased with the volume of organic solvent, recovery in polar MeOH remains incomplete also for less polar lipid classes such as ceramides. Addition of stable isotope-labeled internal standards prior to lipid extraction could compensate for insufficient lipid recovery for polar lipid classes including lysolipids and phospholipids but not for nonpolar CE and TG. In summary, application of one-phase extractions should be limited to polar lipid classes unless sufficient recovery/solubility of nonpolar lipids has been demonstrated. The presented data reveal that appropriate lipid extraction efficiency is fundamental to achieve accurate lipid quantification.
Efficacy and Safety of Telaglenastat Plus Cabozantinib vs Placebo Plus Cabozantinib in Patients With Advanced Renal Cell Carcinoma: The CANTATA Randomized Clinical Trial.

Importance Dysregulated metabolism is a hallmark of renal cell carcinoma (RCC). Glutaminase is a key enzyme that fuels tumor growth by converting glutamine to glutamate. Telaglenastat is an investigational, first-in-class, selective, oral glutaminase inhibitor that blocks glutamine utilization and downstream pathways. Preclinically, telaglenastat synergized with cabozantinib, a VEGFR2/MET/AXL inhibitor, in RCC models. Objective To compare the efficacy and safety of telaglenastat plus cabozantinib (Tela + Cabo) vs placebo plus cabozantinib (Pbo + Cabo). Design, Setting, and Participants CANTATA was a randomized, placebo-controlled, double-blind, pivotal trial conducted at sites in the US, Europe, Australia, and New Zealand. Eligible patients had metastatic clear-cell RCC following progression on 1 to 2 prior lines of therapy, including 1 or more antiangiogenic therapies or nivolumab plus ipilimumab. The data cutoff date was August 31, 2020. Data analysis was performed from December 2020 to February 2021. Interventions Patients were randomized 1:1 to receive oral cabozantinib (60 mg daily) with either telaglenastat (800 mg twice daily) or placebo until disease progression or unacceptable toxicity. Main Outcomes and Measures The primary end point was progression-free survival (Response Evaluation Criteria in Solid Tumors version 1.1) assessed by blinded independent radiology review. Results A total of 444 patients were randomized: 221 to Tela + Cabo (median [range] age, 61 [21-81] years; 47 [21%] women and 174 [79%] men) and 223 to Pbo + Cabo (median [range] age, 62 [29-83] years; 68 [30%] women and 155 [70%] men). A total of 276 (62%) patients had received prior immune checkpoint inhibitors, including 128 with prior nivolumab plus ipilimumab, 93 of whom had not received prior antiangiogenic therapy. Median progression-free survival was 9.2 months for Tela + Cabo vs 9.3 months for Pbo + Cabo (HR, 0.94; 95% CI, 0.74-1.21; P = .65). Overall response rates were 31% (69 of 221) with Tela + Cabo vs 28% (62 of 223) with Pbo + Cabo. Treatment-emergent adverse event (TEAE) rates were similar between arms. Grade 3 to 4 TEAEs occurred in 160 patients (71%) with Tela + Cabo and 172 patients (79%) with Pbo + Cabo and included hypertension (38 patients [17%] vs 40 patients [18%]) and diarrhea (34 patients [15%] vs 29 patients [13%]). Cabozantinib was discontinued due to AEs in 23 patients (10%) receiving Tela + Cabo and 33 patients (15%) receiving Pbo + Cabo. Conclusions and Relevance In this randomized clinical trial, telaglenastat did not improve the efficacy of cabozantinib in metastatic RCC. Tela + Cabo was well tolerated with AEs consistent with the known risks of both agents. Trial Registration ClinicalTrials.gov Identifier: NCT03428217.
Adult ADHD Treatment Based on Combination of Dialectical Behavior Therapy (DBT) and Transcranial Direct Current Stimulation (tDCS) as Measured by Subjective and Objective Scales

Almost 30% of ADHD adults do not respond to standard pharmaceuticals. Transcranial direct current stimulation (tDCS) is a method for modulation of cortical excitability. On the other hand, dialectical behavioral therapy (DBT) is a cognitive-behavioral approach that might be utilized for adults with ADHD. The effects of integration of these interventions are only beginning to be explored. In the present work, we used both subjective and objective measures to investigate the effects of tDCS, DBT, and the integration of the two in treating adult ADHD symptoms. A total of 80 adults with ADHD (63 females, 17 males) participated in the study and were grouped into control, DBT, tDCS, and combined groups. Based on the observed results, the combination of DBT and tDCS was significantly effective in improving the mentioned variables compared to administration of each method in isolation. The results are discussed in terms of neurophysiological and psychological aspects of treatment methods.
Bacteriological quality and antimicrobial susceptibility profiles of isolates of ready-to-eat raw minced meat from hotels and restaurants in Arba Minch, Ethiopia

In Ethiopia, the bacteriological quality of ready-to-eat raw meat is of a great public health concern as it can serve as a source of meat-borne pathogens and worsen the transmission of antimicrobial resistant bacteria, and hence this cross-sectional study, done on 257 meat samples (ie., 169 beef, 50 mutton and 38 chevon) from randomly selected hotels and restaurants (n = 52). Approximately 25 gm of meat samples were taken bi-weekly and subjected to quantitative and qualitative analyses; antimicrobial susceptibility tests were done as per the Kirby-Bauer disk diffusion method. It was found that 13.2 (n = 34), 17.5 (n = 45) and 21.8% (n = 56) samples exceeded the permissible limit for total viable and coliform and S. aureus counts, respectively. At the same time, 24.9% (n = 64) surpassed the bacteriological limit permissible for consumption. Overall, 36.6% (n = 94) of samples were extrapolated as unsatisfactory for consumption due to high bacterial load and or the presence of pathogens. Five different bacterial spp. such as E. coli 65% (n = 167), S. aureus 59% (n = 152), Salmonella spp. 28.4% (n = 73), Campylobacter spp. 14.4% (n = 37) and Shigella spp. 4.3% (n = 11) were isolated in varied proportions. Alarmingly, 60% (n = 264) of the isolates were multi-drug resistant and 51% of S. aureus were found to be MRSA.
Rapid, recurring, structured survey versus bioblitz for generating biodiversity data and analysis with a multispecies abundance model

A bioblitz inexpensively and quickly generates biodiversity data, but bioblitzes are often conducted with haphazard, unreplicated sampling. Results tend to be taxonomically, geographically, or temporally biased, lack metadata, and consist of lists of observed taxa that do not enable further analyses or correction for imperfect detection. A rapid, recurring, structured survey (RRSS) uses a structured sampling design and temporal and spatial replication to survey randomly selected sites on a conservation property. We participated in a loosely structured bioblitz and a subsequent RRSS at Big Canoe Creek Nature Preserve in Springville (St. Clair County), Alabama (USA) to compare observed richness derived from the 2 survey approaches. The RRSS data structure enabled us to fit models that accounted for imperfect detection to estimate abundances, occupancy probabilities, and habitat associations. The loosely structured bioblitz data could not be used in such models. We present a new integrated multispecies abundance model that we applied to avian RRSS data. Our model extension enables estimation for the community, employs data augmentation to estimate the number of undetected species, and incorporates covariates. The RRSS generated a more comprehensive and less biased list of observed taxonomic richness than the loosely structured bioblitz (e.g., 73 vs. 45 bird species and 104 vs. 63 insect families from the RRSS vs. loosely structured bioblitz, respectively). Models fit to the RRSS data identified seasonal patterns in avian community composition and allowed for estimation of habitat–occupancy relationships for insect taxa. The RRSS protocol has potential for broad transferability as a standardized, quick, and inexpensive way to inventory biodiversity and estimate ecological parameters while providing an outreach opportunity.
Optimized Infliximab Induction Predicts Better Long-Term Clinical and Biomarker Outcomes Compared to Standard Induction Dosing

Objectives: To evaluate the efficacy of standard and optimized infliximab induction dosing in attaining corticosteroid (CS) free clinical remission at week 52 and the effect that post-induction trough levels have on long-term outcome. Methods: Inflammatory bowel disease (IBD) patients ≤18 years commenced on infliximab between August 1, 2016, and August 1, 2018, from Vancouver, Canada, and Glasgow, Scotland, were included. The Glasgow cohort followed standard induction while the Vancouver cohort undertook induction optimization based on clinical, biomarker, and proactive infliximab trough levels. Baseline characteristics and laboratory values were documented. Results: In total, 140 children were included [median age 14.1 years (interquartile range (IQR) 12.0–16.0)]; 54% male. CS-free clinical remission at week 52 was higher in the optimized group compared to the standard cohort [65/78 (83%) vs. 32/62 (52%), P < 0.001]. Combined CS-free clinical and biomarker remission (CRP < 5 mg/L) was also higher in the optimized compared to the standard cohort [65/78 (83%) vs 25/62 (40%), P < 0.001]. The median post-induction trough level was higher in children who were in CS-free clinical remission at week 52 [3.6 mg/L (1.5-7.1)] vs. those who were not [2.0 mg/L (0.8–4.1), P = 0.04]. The odds of attaining a therapeutic post-induction trough level were almost 4-fold higher in the optimized group than the standard cohort (OR 3.97, 95% CI: 1.89–8.68, P < 0.001). Conclusions: Standard infliximab induction resulted in less favorable long-term outcomes for pediatric IBD patients. Optimizing induction using clinical, biomarker, and proactive trough levels resulted in higher post-induction trough levels and a greater odds of attaining long-term clinical remission.
A Systematic Review of Community-Level Protective Factors in Children Exposed to Maltreatment

Childhood maltreatment and neglect are associated with a host of negative outcomes. Yet, some children show resilience despite their exposure to these traumatic events. Several protective factors have been documented in the literature, but few studies focus on protective factors in the child’s community that can promote resilience. The purpose of this review was to provide a comprehensive portrait of the impact of community protective factors on the resilience of abused and neglected children. The databases PsycNet and PubMed were used to screen the literature relying on the following inclusion criteria: (1) published in English or in French; (2) report empirical and quantitative data; (3) include a minimum sample size of 30 participants; (4) rely on a sample of maltreated children or adolescents under the age of 24; (5) examine the associations between community protective factors and indicators of psychological adaptation; and (6) include outcome measures that assessed either positive adaptation or the absence of symptomatology in participants. Of the 9,553 articles identified, 44 studies met the eligibility criteria for inclusion in this review. Although many protective factors show significant results, several methodological limitations remain to be examined to affirm that these community variables have a significant impact on the level of resilience of maltreated children. Since child maltreatment is a systemic issue, it remains important to fully understand how community protective factors operate on the resilience of these children as it can greatly inform practitioners and community institutions on how to intervene with populations at risk of maltreatment.
Resonator-QWIP FPA development

Previously, we adopted the resonator-QWIPs and increased the FPA QE to 30 − 40%. In this work, we performed a systematic theoretical analysis on the potential performance based on this new detector structure. In this analysis, the doping density and the number of quantum wells are varied to obtain different detector characteristics. For 25 μm pixel pitch, 10 Me− integrated charge, and F/2 optics, the analysis shows that a 9.2 μm cutoff R-QWIP optimized for high temperature operation could provide 20 mK NEΔT at τint = 2.6 ms when operating at T = 80 K. An R-QWIP with a 10.2 μm cutoff could achieve the same with τint = 1.3 ms at T = 74 K. Similar NEΔT can also be achieved with smaller pixel pitch down to 6 μm for both cutoffs with a more relaxed operating condition where the f-number is 1, τint is 5 ms, and T is 70 K. We provide preliminary test detector data to support this analysis.
Migratory routes, breeding locations and multiple non-breeding sites of Common Whitethroats Curruca communis revealed by geolocators

Understanding general migration characteristics and how breeding and non-breeding sites are connected is crucial for predicting the response of long-distance migratory bird populations to environmental changes. We use data collected from six geolocators to describe migratory routes and identify breeding and non-breeding locations, migratory behaviour and differences between spring and autumn migration of Common Whitethroats Curruca communis, an Afro-Palearctic migrant, wintering in Nigeria. Most individuals departed on spring migration in April, following a north-easterly direction, arriving at their breeding grounds across central-eastern Europe (~425,000 km2) in May. Departures from breeding grounds took place between July and August in a south-westerly direction. During spring migration individuals travelled longer distances at faster rates making its overall duration shorter than autumn migration. We suggest that, while Whitethroats can cross the Sahara Desert and Mediterranean Sea in a single flight, they are likely to refuel before and after crossing. Results indicate that Whitethroats undertook loop migration and visited two wintering sites: first in the Sahel, then in Nigeria, where they remained until spring migration. Geolocator results and data from the European Union for Bird Migration’s (EURING) ringing database suggest that Whitethroats have a relatively high migratory spread—individuals from a single non-breeding site breed across a wide area of Europe. Our research is the first to track and describe the complete annual cycle of Whitethroats and one of the few studies to do so for any Afro-Palearctic migrant from non-breeding grounds. We identified the Sahel as an important refuelling and first wintering site indicating its conservation, alongside other stopover sites, is crucial for the species. We believe that changes in this region will have severe effects on a subset of individuals of specific European breeding populations, but these effects will greatly depend on the severity of the changes and at what spatial scale they occur.
Iterative phase contrast CT reconstruction with novel tomographic operator and data-driven prior

Breast cancer remains the most prevalent malignancy in women in many countries around the world, thus calling for better imaging technologies to improve screening and diagnosis. Grating interferometry (GI)-based phase contrast X-ray CT is a promising technique which could make the transition to clinical practice and improve breast cancer diagnosis by combining the high three-dimensional resolution of conventional CT with higher soft-tissue contrast. Unfortunately though, obtaining high-quality images is challenging. Grating fabrication defects and photon starvation lead to high noise amplitudes in the measured data. Moreover, the highly ill-conditioned differential nature of the GI-CT forward operator renders the inversion from corrupted data even more cumbersome. In this paper, we propose a novel regularized iterative reconstruction algorithm with an improved tomographic operator and a powerful data-driven regularizer to tackle this challenging inverse problem. Our algorithm combines the L-BFGS optimization scheme with a data-driven prior parameterized by a deep neural network. Importantly, we propose a novel regularization strategy to ensure that the trained network is non-expansive, which is critical for the convergence and stability analysis we provide. We empirically show that the proposed method achieves high quality images, both on simulated data as well as on real measurements.
Development of a Root Caries Prediction Model in a Population of Dental Attenders

Root caries prevalence is increasing as populations age and retain more of their natural dentition. However, there is generally no accepted practice to identify individuals at risk of disease. There is a need for the development of a root caries prediction model to support clinicians to guide targeted prevention strategies. The aim of this study was to develop a prediction model for root caries in a population of regular dental attenders. Clinical and patient-reported predictors were collected at baseline by routine clinical examination and patient questionnaires. Clinical examinations were conducted at the 4-year timepoint by trained outcome assessors blind to baseline data to record root caries data at two thresholds – root caries present on any teeth (RC > 0) and root caries present on three or more teeth (RC ≥ 3). Multiple logistic regression analyses were performed with the number of participants with root caries at each outcome threshold utilized as the outcome and baseline predictors as the candidate predictors. An automatic backwards elimination process was conducted to select predictors for the final model at each threshold. The sensitivity, specificity, and c-statistic of each model’s performance was assessed. A total of 1,432 patient participants were included within this prediction model, with 324 (22.6%) presenting with at least one root caries lesion, and 97 (6.8%) with lesions on three or more teeth. The final prediction model at the RC >0 threshold included increasing age, having ≥9 restored teeth at baseline, smoking, lack of knowledge of spitting toothpaste without rinsing following toothbrushing, decreasing dental anxiety, and worsening OHRQoL. The model sensitivity was 71.4%, specificity 69.5%, and c-statistic 0.79 (95% CI: 0.76, 0.81). The predictors included in the final prediction model at the RC ≥ 3 threshold included increasing age, smoking, and lack of knowledge of spitting toothpaste without rinsing following toothbrushing. The model sensitivity was 76.5%, specificity 73.6%, and c-statistic 0.81 (95% CI: 0.77, 0.86). To the authors’ knowledge, this is the largest published root caries prediction model, with statistics indicating good model fit and providing confidence in its robustness. The performance of the risk model indicates that adults at risk of developing root caries can be accurately identified, with superior performance in the identification of adults at risk of multiple lesions.
Overview of systematic reviews: Management of common Traumatic Brain Injury-related complications

Background Many clinical interventions are trialled to manage medical complications following Traumatic Brain Injury (TBI). However, published evidence for the effects of those clinical interventions is limited. This article is an overview of common complications and their management from published systematic reviews in TBI. Methods and findings A health science electronic database search for published systematic reviews for management of common complications in TBI was conducted in the last decade till 31st January 2021. Methodological quality and evidence were critically appraised using the Grading of Recommendations, Assessment, Development and Evaluations and Revised-Assessment of Multiple Systematic review tools. Overall, only six systematic reviews complied with search criteria, these evaluated fatigue, spasticity and post traumatic seizures (29 RCTs, 13 cohort studies, n = 5639 participants). No systematic reviews for other common TBI-related complications met criteria for this review. The included reviews varied from ‘moderate to high’ in methodological quality. The findings suggest beneficial treatment effect of anti-epileptic drugs (phenytoin/levetiracetam) compared with placebo in reducing early seizure incidence, but no significant benefit of phenytoin over levetiracetam, valproate, or neuroprotective agent for early or late posttraumatic seizures. There was ‘limited’ evidence for spasticity-related interventions, and ‘insufficient’ evidence of cardiorespiratory training on fatigue levels. Conclusions Despite the high prevalence and associated functional impact of TBI-related complications, there is limited evidence to guide treating clinicians for management of common TBI complications. More robust studies are needed to build evidence in this population.
Lead-free piezoceramics with giant strain in the system Bi0.5Na0.5TiO3–BaTiO3–K0.5Na0.5NbO3. II. Temperature dependent properties

The temperature dependence of the dielectric and ferroelectric properties of lead-free piezoceramics of the composition (1−x−y)Bi0.5Na0. 5TiO3–xBaTiO3–yK0.5Na0. 5NbO3 (0.05⩽x⩽0.07, 0.01⩽y⩽0.03) was investigated. Measurements of the polarization and strain hystereses indicate a transition to predominantly antiferroelectric order when heating from room temperature to 150°C, while for 150<T<200°C both remnant polarization and coercive field increase. Frequency-dependent susceptibility measurements show that the transition is relaxorlike. For some samples, the transition temperature Td is high enough to allow mostly ferroelectric ordering at room temperature. These samples show a drastic increase of the usable strain under an external electric field just after the transition into the antiferroelectric state at high temperatures. For the other samples, Td is so low that they display significant antiferroelectric ordering already at room temperature. In these samples, the usable strain is relatively stable over a.