Miracle-dz/UniFAR-FTUs huggingface dataset:
Nicotinic receptor components of amyloid beta 42 proteome regulation in human neural cells

Alzheimer’s disease (AD) is associated with chronic neurodegeneration often accompanied by elevated levels of the neurotoxic peptide amyloid-beta 1–42 (Aβ42) in the brain. Studies show that extracellular Aβ42 binds to various cell surface receptors including the human α7 nicotinic acetylcholine receptor (nAChR) and activates pathways of neurotoxicity leading to cell death. The α7 nAChR is thus considered a promising drug target for therapy against neurodegenerative disease such as AD. In this study, we use mass spectrometry-based label-free precursor ion quantification to identify proteins and pathways that are changed by a 72-hour treatment with Aβ42 or Aβ42 in the presence of the α7 nAChR blocker, α-bungarotoxin (Bgtx) in the human neuroblastoma SH-SY5Y cell line. Bioinformatic gene ontology enrichment analysis was used to identify and characterize proteins and pathways altered by Aβ42 presentation. The results support evidence on the involvement of mitochondrial proteins in Aβ42 responses and define potential mechanisms of α7 nAChR mediated amyloid toxicity. These findings can inform pharmacological strategies for drug design and treatment against amyloid disease.
Information flows from hippocampus to auditory cortex during replay of verbal working memory items

The maintenance of items in working memory (WM) relies on a widespread network of cortical areas and hippocampus where synchronization between electrophysiological recordings reflects functional coupling. We investigated the direction of information flow between auditory cortex and hippocampus while participants heard and then mentally replayed strings of letters in WM by activating their phonological loop. We recorded local field potentials from the hippocampus, reconstructed beamforming sources of scalp EEG, and – additionally in four participants – recorded from subdural cortical electrodes. When analyzing Granger causality, the information flow was from auditory cortex to hippocampus with a peak in the [4 8] Hz range while participants heard the letters. This flow was subsequently reversed during maintenance while participants maintained the letters in memory. The functional interaction between hippocampus and the cortex and the reversal of information flow provide a physiological basis for the encoding of memory items and their active replay during maintenance.
EVALUATING SEPSIS CRITERIA IN DETECTING ALTERATIONS IN CLINICAL, METABOLIC, AND INFLAMMATORY PARAMETERS IN BURN PATIENTS

ABSTRACT Sepsis has become the leading cause of death in burn patients. Furthermore, sepsis and septic complications result in significant morbidities and longer hospitalization, which has profound impacts on the healthcare system. Despite this, sepsis in burn patients is surprisingly poorly understood and characterized. This retrospective, single-institution cohort study aimed to increase our understanding of the septic response after burns. We hypothesized that different sepsis definitions will results in distinctive septic trajectories and biochemical patterns after injury. Sepsis was defined by our burn center–specific prospective definition, the American Burn Association criteria, Sepsis-3 criteria, and the Mann-Salinas criteria. Applying these definitions, we compared clinical, metabolic, and inflammatory markers in septic and nonseptic burn patients. We found that the Sepsis-3 criteria are the most reliable screening tool used before clinical diagnoses for detecting sepsis trajectories and biochemical patterns. Moreover, we characterized distinct temporal alterations in biomarkers during the pre– and post–septic periods in burn patients, which may be incorporated into future sepsis definitions to improve the accuracy of a sepsis diagnosis in burn patients.
Colony specificity and starvation-driven changes in activity patterns of the red ant Myrmica rubra

Although the activity levels of insect societies are assumed to contribute to their ergonomic efficiency, most studies of the temporal organization of ant colony activity have focused on only a few species. Little is known about the variation in activity patterns across colonies and species, and in different environmental contexts. In this study, the activity patterns of colonies of the red ant Myrmica rubra were characterized over 15 consecutive days. The main goals were to evaluate the colony specificity of the activity patterns and the impact of food deprivation on these patterns. We found that the average activity level varied across colonies and remained consistent over 1 week, providing evidence that the activity level is a colony-specific life trait. Furthermore, all colonies applied an energy-saving strategy, decreasing their average levels of activity inside the nest, when starved. Starvation induced no consistent change in the activity level outside of the nest. An analysis of activity time series revealed activity bursts, with nestmates being active (or inactive) together, the amplitudes of which reflected the ants’ degree of synchronization. Food deprivation increased the amplitude and number of these activity bursts. Finally, wavelet analyses of daily activity patterns revealed no evidence of any periodicity of activity bouts occurring inside or outside of the nest. This study showed that M. rubra ant colonies are characterized by specific activity levels that decrease in response to starvation with the adoption of an energy-saving strategy. In addition, our results help to understand the functional value associated with synchronized and/or periodic fluctuation in activity, which has been debated for years.
Editorial for “Arterial Spin Labeling Estimation of Penumbral Tissue in Acute Ischemic Stroke”

Editorial for “Arterial Spin Labeling Estimation of Penumbral Tissue in Acute Ischemic Stroke” Stroke is the leading cause of death and disability worldwide. Endovascular treatment (EVT) has become the standard care for acute large vessel occlusive stroke, and imaging has played a central role in the triage of acute ischemic stroke (AIS) patients for EVT. Ischemic penumbra, which is physiologically defined as the hypoperfused brain tissue at risk of irreversible damage but is potentially salvageable by reperfusion, is a key metric to select AIS patients eligible for EVT. Dynamic contrast-based imaging approaches including computed tomography perfusion (CTP) and magnetic resonance (MR) perfusion, though not the gold standard of penumbra imaging, are feasible to capture the tissue at risk in clinical scenarios by detecting a mismatch pattern between ischemic penumbra and infarct core. These methods share the advantages of rapid scanning, providing multiple perfusion parameters. However, these methods require contrast agents with the risk of allergic reactions and supply chain shortage. Technically, ischemic penumbra is operationally defined as areas with time-to-maximum of residue function (Tmax) > 6 seconds, 2
Job Demands May Determine Cognitive and Physical Aging After Retirement

During adulthood, we spend most of our time and efforts at work. However, the impact of employment in aging is poorly explored. Our study addressed how job demands can affect aging after retirement. We have developed a descriptive observational study carried out in 367 older adults with a mean age of 73.9 years (66.5% women and 33.5% men), measuring cognition and functional status. Our results demonstrate that older adults who had high mental demands in their jobs, show better scores in cognition. However, they show poor functional development of basic and instrumental activities of daily life (p< .05). In contrast, former workers who had high physical demands, display lower scores in cognition and lower functional performance in instrumental activities (p< .05). Work life activities contribute to cognitive and physical decline after retirement. Therefore, healthy aging should include interventions that consider the job influence on the age impairment.
Parkinson's disease and iatrogenic impulsive-compulsive behaviors: A case/non-case study to build a complete model of individual vulnerability

Abstract Background and aims Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases. First-line medications consist of drugs that act by counteracting dopamine deficiency in the basal ganglia. Unfortunately, iatrogenic impulsive-compulsive behaviors (ICBs) can occur in up to 20% of PD patients over the course of their illness. ICBs must be considered multifactorial disorders that reflect the interactions of the medication with an individual's vulnerability and the underlying neurobiology of PD. We aimed to explore the predictive genetic, psychopathological and neurological factors involved in the development of ICBs in PD patients by building a complete model of individual vulnerability. Methods The PARKADD study was a case/non-case study. A total of 225 patients were enrolled (“ICB” group, N = 75; “no ICB” group, N = 150), and 163 agreed to provide saliva samples for genetic analysis. Sociodemographic, neurological and psychiatric characteristics were assessed, and genotyping for the characterization of polymorphisms related to dopaminergic and opioid systems was performed. Results Factors associated with “ICBs” were younger age of PD onset, personal history of ICB prior to PD onset and higher scores on the urgency and sensation seeking facets of impulsivity. No gene variant was significantly associated, but the association with the opioid receptor mu 1 (OPRM1) rs1799971 polymorphism was close to significance. Discussion and conclusions The influence of gene-environment interactions probably exists, and additional studies are needed to decipher the possible role of the opioid system in the development of ICBs in PD patients.
Intraobserver Reliability on Classifying Bursitis on Shoulder Ultrasound

Purpose: Bursitis is a common musculoskeletal cause of shoulder pain and treatment varies, thus correctly diagnosing and grading bursitis is paramount in deciding management. Our aim was to assess reliability in grading shoulder bursitis on ultrasonography among fellowship trained musculoskeletal radiologists at our institution. Methods: Retrospective study of patients diagnosed with bursitis on ultrasonography. Single-sonographic images of the subacromial-subdeltoid bursa were collected for each patient and randomized to form a test-bank of varying degrees of bursitis. Three months after the test was administered, the cases were randomized and readministered. The radiologists graded each case as: within normal limits, mild, moderate or severe. Intraobserver variability was measured using Cohen’s kappa coefficient. Linear regression model was performed to assess correlation between years of experience and kappa. Results: 10 radiologists reviewed 70 cases of bursitis. Kappa values ranged from . 53 to . 91, indicating ‘moderate’ to ‘almost perfect’ variability amongst radiologists. A moderate positive correlation of improving variability (r = .69) with increasing years of experience exists. Conclusion: Fellowship trained musculoskeletal radiologists were able to grade shoulder bursitis with moderate to almost perfect variability, with a positive correlation of improved variability with increasing experience. This may help clinicians choose the correct treatment more confidently in their patients with shoulder pain.
Detecting and quantifying antibody reactivity in PhIP-Seq data with BEER

Abstract Summary Because of their high abundance, easy accessibility in peripheral blood, and relative stability ex vivo, antibodies serve as excellent records of environmental exposures and immune responses. Phage Immuno-Precipitation Sequencing (PhIP-Seq) is the most efficient technique available for assessing antibody binding to hundreds of thousands of peptides at a cohort scale. PhIP-Seq is a high-throughput approach for assessing antibody reactivity to hundreds of thousands of candidate epitopes. Accurate detection of weakly reactive peptides is particularly important for characterizing the development and decline of antibody responses. Here, we present BEER (Bayesian Enrichment Estimation in R), a software package specifically developed for the quantification of peptide reactivity from PhIP-Seq experiments. BEER implements a hierarchical model and produces posterior probabilities for peptide reactivity and a fold change estimate to quantify the magnitude. BEER also offers functionality to infer peptide reactivity based on the edgeR package, though the improvement in speed is offset by slightly lower sensitivity compared to the Bayesian approach, specifically for weakly reactive peptides. Availability and implementation BEER is implemented in R and freely available from the Bioconductor repository at https://bioconductor.org/packages/release/bioc/html/beer.html.
Improving CH4/O2 energy ratio of meat processing wastewater treatment systems through micro-sieving

ABSTRACT Micro-sieving is an effective way to prevent organic pollutants enter the main biological process and reduce aeration intensity and sludge production. However, few researchers quantified the effect of micro-sieving on meat processing wastewater treatment. The current study developed Excel-based models to compare the energy consumption and production of historical, conventional and innovative systems. Historical and conventional systems employ activated sludge (AS), nitrification, and denitrification as the main biological processes. Innovative systems are designed by using up-flow anaerobic sludge blanket (UASB) and partial nitrification/Anammox (PN/A) as the main treatment processes. Results show that the CH4/O2 energy ratios of the innovative treatment system are as high as 10 times of the historical and conventional systems. Therefore, innovative system can achieve electrical self-sufficiency. Micro-sieving reduces 5% of aeration demand. Furthermore, the impact of micro-sieving on the innovative treatment systemis assessed by cost-benefit analysis. System with micro-sieving has the shortest payback time of 2.1 years and reduces cost of the innovative treatment system. An excel-based model was developed to quantify the impact of micro-sieving on energy and cost of innovative treatment system, thereby providing a valuable reference for future sustainable engineering design of meat processing wastewater treatment. GRAPHICAL ABSTRACT
Genomic analysis of the rare British Lop pig and identification of distinctive genomic markers

Concentration of production on a few commercial pig breeds has led to the marginalization of many native, numerically small breeds, increasing their risk of endangerment. In the UK, one such rare breed is the British Lop, a lop-eared breed, of similar origin to the Welsh breed. The objective of the present study was to address the genomic status of the British Lop and its relationship with other breeds and identify a small set of genomic markers that uniquely characterize and distinguish British Lop animals. Results have shown that the British Lop is a relatively distinct population with reduced genomic diversity and effective size consistent with its status as a rare breed. Furthermore, we demonstrated the genetic closeness of the British Lop to phenotypically similar breeds such as Landrace and Welsh as well Large White, Middle White and Pietrain. Finally, a set of 75 Single Nucleotide Polymorphisms distributed across multiple chromosomes were identified and validated as markers that can consistently distinguish British Lops from other closely related breeds. Results may inform breeding and management strategies aiming to enhance diversity as well as the development of a breed purity test.
Development of continuous-wave Tm:YAlO₃ lasers for high power applications

Thulium and holmium lasers operating near 2 μm are required for applications in various industries, such as remote sensing and detection, spectroscopy, surgery and optical countermeasures. High power lasers with high brightness are necessary for many of these applications, with fibre lasers often preferred due to their various advantages. However, a major drawback of fibre lasers is the brightness requirement on the pump source, which needs to have moderate to high brightness in order to couple light into the fibres efficiently. Such pump sources are often prohibitively expensive. A possible solution is the use of brightness converters. Brightness converters are lasers that are designed such that the output brightness is significantly greater than that of its pump source, and is sufficiently bright to pump fibre lasers efficiently. For example, by using a thulium-doped solid-state laser as a brightness converter, holmiumdoped fibre lasers can be pumped efficiently by cheap, high power but low brightness diode stacks. Thulium-doped YAlO3 lasers are ideal for this purpose: their emission wavelength corresponds to the peak absorption of holmium in silica, high power diode stacks are readily available at its absorption wavelength, and it is a crystal with a high damage threshold. However, Tm:YAlO3 lasers suffer from significant self-pulsing, which can lead to unstable gain-switching of the holmium-doped fibre laser as well as risking damage due to the high peak power. In this thesis, I describe the investigation and development of Tm:YAlO3 lasers as high power brightness converters and pump sources. A detailed analysis of the selfpulsing is conducted using a 6.5 W Tm:YAlO3 laser. The self-pulsing is shown initially to be consistent with an unstable relaxation oscillation in the gain medium. A model based on significant excited-state absorption at the lasing wavelength is shown to reproduce the experimental results. The assumed cross-section required for this
Monotherapy and combination chemotherapy for Chagas disease treatment: a systematic review of clinical efficacy and safety based on randomized controlled trials

Abstract Abstract From a systematic review framework, we analysed the clinical evidence on the effectiveness and safety of monotherapy and combination chemotherapy for Chagas disease (ChD) treatment. The research protocol was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and patient, intervention, comparison and outcome strategy. Only randomized controlled trials (RCT) were retrieved from Embase, Medline, Scopus and Web of Science databases. Diagnostic tools, treatment protocols, seroconversion rates and adverse events were investigated. Fifteen RCT mainly concentrated in endemic countries were identified. ChD diagnosis was mainly based on haemagglutination, immunofluorescence, enzyme-linked immunosorbent assay and polymerase chain reaction. Benznidazole (BNZ), nifurtimox, fosravuconazole, posaconazole, allopurinol and thioctic acid were the identified drugs. The best negative seroconversion results (100, 96, 94 and 91.3%) were, respectively, based on BNZ (5 mg kg day−1, 200 mg day−1, 150 mg day−1 and 2.5 mg kg−1) administration for 60 days. Negative seroconversion was not achieved with allopurinol (300 mg day−1 for 60 days). Adverse reactions ranged from 5 to 73% in patients receiving antiparasitic chemotherapy. Treatment discontinuation (1.5–57%) was mainly associated with gastrointestinal, cutaneous and neurological manifestations. Current RCT-based evidence indicates that BNZ is the most viable option for ChD treatment. However, new protocols need to be developed to mitigate side effects and increase patient adherence to antiparasitic chemotherapy. Therefore, shorter regimens, lower concentrations and treatments combining BNZ with posaconazole, fosravuconazole or ravuconazole may be viable to ensure comparable efficacy to BZN-based monotherapy, contributing to reduce dose- and time-dependent toxicity reactions.
The role of community health workers in influencing social connectedness using the household model: a qualitative case study from Malawi

ABSTRACT Background Community health workers (CHWs) play a vital role in facilitating social connectedness, building trust, decrease stigma, and link communities to essential healthcare and social support services. More studies are needed to understand the factors facilitating these interactions among CHWs, clients, and community members. Objective This study examined the CHW role and relationships between CHWs, communities, and health facilities that promote trust, positive relationships, and social connectedness. Methods In 2016, the CHW program in Neno District, Malawi, was transitioned to a household-level assignment of CHWs to provide screening, linkage to care, and psychosocial and chronic disease support from a disease-based program. We employed an exploratory qualitative study with thematic analysis linked to Fredrickson’s broaden-and-build theory of positive emotions through focus group discussions (FGDs) and in-depth interviews (IDIs) to understand the impact of the household assignment. We purposively sampled community stakeholders, CHWs, health service providers, and clients (total N = 180) from October 2018 through March 2020. All interviews were audiotaped, transcribed verbatim, translated, coded, and analyzed. Results Participants reported decreased stigma and discrimination with increased trust and confidence in CHWs with household-level assignment. Positive relationships between CHWs in their households, community members, and health facility staff fostered health knowledge, individual agency, and personal resources for the community members to access health services. Community members’ personal resources of increased health knowledge, trust, gratitude, and social support improved social connectedness and subjective wellbeing. Areas to improve positive relationships include CHWs maintaining confidentiality and caring for pregnant women. Conclusion Our study findings demonstrate that by building solid relationships as a community chosen, well informed, and household-level workforce, CHWs can develop positive relationships with communities and the health-care facility staff through building knowledge, trust, gratitude, and hope. Further work is needed in maintaining CHW confidentiality and new ways to approach culturally sensitive health areas.
Defining Long-Term-Care Need Levels for Older Adults: Towards a Standardized European Classification

ABSTRACT International comparisons of long-term care (LTC) are hampered by inconsistencies in how to define the need for care. This is especially relevant for the European Union, whose Aging Working Group, which is tasked to project aging expenditure in the long term, has over time used two competing definitions – one based on inability to perform Activities of Daily Living (ADL) and another based on the more subjective Global Activity Limitation Index (GALI). The inconsistency in measurement, as well as problems in defining the intensity of needs, will acquire growing significance as longevity progresses. This paper investigates how the two measures are linked, by analyzing a large European sample survey where respondents replied to both questions. This allows a calibration of the two measures and an investigation of their areas of overlap and difference. The paper concludes by proposing a simple new 4-scale measure of care needs which, by combining the two metrics, introduces some gradation of the intensity of care. Using a consistent measure incorporating intensity, such as the one proposed, will facilitate international comparisons, improve long-term expenditure projections, and aid policy discussion, including the transfer of best practice.