Miracle-dz/UniFAR-FTUs huggingface dataset:
The Landscape of Parkin Variants Reveals Pathogenic Mechanisms and Therapeutic Targets in Parkinson's Disease.

Mutations in Parkin (PARK2), which encodes an E3 ubiquitin ligase implicated in mitophagy, are the most common cause of early onset Parkinson's Disease (PD). Hundreds of naturally occurring Parkin variants have been reported, both in PD patient and population databases. However, the effects of the majority of these variants on the function of Parkin and in PD pathogenesis remains unknown. Here we develop a framework for classification of the pathogenicity of Parkin variants based on the integration of clinical and functional evidence - including measures of mitophagy and protein stability, and predictive structural modeling - and assess 51 naturally occurring Parkin variants accordingly. Surprisingly, only a minority of Parkin variants, even among those previously associated with PD, disrupted Parkin function. Moreover, a few of these naturally occurring Parkin variants actually enhanced mitophagy. Interestingly, impaired mitophagy in several of the most common pathogenic Parkin variants could be rescued both by naturally-occurring (p.V224A) and structure-guided designer (p.W403A; p.F146A) hyperactive Parkin variants. Together, the findings provide a coherent framework to classify Parkin variants based on pathogenicity and suggest that several pathogenic Parkin variants represent promising targets to stratify patients for genotype-specific drug design.
Encoding-phase orientation toward thematic content over perceptual style benefits picture memory

ABSTRACT Orienting toward the meaning versus perceptual features of an experience benefits subsequent memory. Yet given that past work encouraged these orientations with different tasks, it is not clear if this memory benefit is solely due to internal processing factors versus external task-related ones. Moreover, it remains unclear how this benefit generalises from verbal to detailed picture memory. Here, we developed a novel paradigm that cued participants’ attention to thematic (story) or stylistic (artist style) dimensions of storybook-style illustrations during a repeat-detection task. Afterwards, participants completed a recognition memory test with studied illustrations and lures along thematic and stylistic dimensions. In contrast to past work, both orienting tasks were identical except for the dimension participants were cued to attend to. Furthermore, our thematic and stylistic dimensions enabled us to separately examine memory quality along each dimension. We found that thematic attention yielded superior memory for studied illustrations over stylistic orientations. False alarms to lures varied by dimension and attention: errors were greater to thematic than stylistic lures overall and stylistic attention elevated false alarms to stylistic lures. Our results show that semantic encoding orientations enhance detailed picture memory, without a cost to memory quality along semantic or perceptual dimensions of experience.
Weak universal critical behaviour of the mixed spin‐(1/2, S ) Ising model on the Union Jack (centered square) lattice: integer versus half‐odd‐integer spin‐S case

The mixed spin‐(1/2, S ) Ising model on the Union Jack (centered square) lattice is investigated by establishing the mapping relationship with its corresponding eight‐vertex model. An interplay between the nearest‐neighbour interaction, the competing next‐nearest‐neighbour interaction and the single‐ion anisotropy gives rise to a rather complex critical behaviour displayed in the reentrant phase transitions, the weak universal critical behaviour, as well as, a presence of first‐ and second‐order phase transitions. The most interesting finding to emerge from the present study relates to a variation of the weak‐universal critical exponents along the line of bicritical points, which is being twice as large for the mixed spin‐(1/2, S ) systems with the integer spin‐S atoms as for the ones with the half‐odd‐integer spin‐S atoms. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Atomic emission and cavity field spectra for a two-photon Jaynes–Cummings model in the presence of the Stark shift

The emission spectrum of the atom and the cavity field spectrum of the two-photon Jaynes–Cummings model are studied, with the input field assumed to be in a number state, a thermal state, a squeezed vacuum state, and a coherent state. The effects of the Stark shift are highlighted. Both the emission and the cavity field spectra show central two-peak structures and no sidebands. A comparison with the one-photon Jaynes–Cummings model is carried out.
Numerical Methods in Structural Dynamics

The dynamic analysis of a structure subjected to a random forcing function from a source such as earthquake, blast, or wind requires the use of a numerical integration technique. The efficiency and accuracy of the technique employed is of great importance for both research and practical design. The more effective methods of numerical integration belong to the category designated as ‘predictor-corrector’ methods. A systematic method is presented for the derivation of single-point and multiple-point predictor-corrector formulae. It is shown that most of the methods of numerical integration presently employed in structural dynamics are single-point predictor-corrector methods. A scheme of iteration is usually employed for the solution of the difference equations obtained by the application of these methods. It is shown that for problems in structural dynamics, it is not necessary to use an iterative scheme; a process of elimination is feasible and also gives considerable economy in computation time. It is fu.
Superconductivity in High Tc Cuprates: The Cause is No Longer A Mystery

I discuss various direct calculations of the properties of the one-band Hubbard model on a square lattice and conclude that these properties sufficiently resemble those of the cuprate superconductors that no more complicated interactions are necessary to cause high Tc superconductivity. In particular, I discuss phonon effects and conclude that these may be effective in reducing Tc and the gap in electron-doped materials.
Shift workers are at increased risk of severe COVID-19 compared with day workers: Results from the international COVID sleep study (ICOSS) of 7141 workers

ABSTRACT The present study had two main aims. First, to investigate whether shift/night workers had a higher prevalence and severity of COVID-19 compared with day workers. Second, to investigate whether people regularly working in face-to-face settings during the pandemic exhibited a higher prevalence and severity of COVID-19 compared with those having no need to be in close contact with others at work. Data consisted of 7141 workers from 15 countries and four continents who participated in the International COVID Sleep Study-II (ICOSS-II) between May and December 2021. The associations between work status and a positive COVID-19 test and several indications of disease severity were tested with chi-square tests and logistic regressions adjusted for relevant confounders. In addition, statistical analyses were conducted for the associations between face-to-face work and COVID-19 status. Results showed that shift/night work was not associated with an increased risk of COVID-19 compared to day work. Still, shift/night workers reported higher odds for moderate to life-threatening COVID-19 (adjusted odds ratio (aOR) = 2.71, 95%-confidence interval = 1.23–5.95) and need for hospital care (aOR = 5.66, 1.89–16.95). Face-to-face work was associated with an increased risk of COVID-19 (aOR = 1.55, 1.12–2.14) but not with higher disease severity. In conclusion, shift/night work was not associated with an increased risk of COVID-19, but when infected, shift/night workers reported more severe disease. Impaired sleep and circadian disruption commonly seen among shift/night workers may be mediating factors. Working face-to-face increased the risk of COVID-19, likely due to increased exposure to the virus. However, face-to-face work was not associated with increased disease severity.
The Biomechanical Effects of Different Bag‐Carrying Styles on Lumbar Spine and Paraspinal Muscles: A Combined Musculoskeletal and Finite Element Study

Bags such as handbags, shoulder bags, and backpacks are commonly used. However, it is difficult to assess the biomechanical effects of bag‐carrying styles on the lumbar spine and paraspinal muscles using traditional methods. This study aimed to evaluate the biomechanical effects of bag‐carrying styles on the lumbar spine.
The general health status of newly arrived asylum seekers in Denmark

Aims: The number of asylum seekers in Europe is increasing and is likely to do so continuously due to conflicts, poverty and climate. Asylum seekers are exposed to many health risk factors related to their migration process and this study aimed to explore their general health status on arrival at an immigration country. Methods: A retrospective study including 1907 general health assessments (GHAs) of adult asylum seekers arriving in Denmark between 1 September 2017 and 31 December 2019 was undertaken. The GHA is offered to all adult asylum seekers as part of the health-care reception programme. Only asylum seekers who attended the GHA within 1 month of their arrival in Denmark were included. Data comprised sociodemographic factors, health outcomes, and indication of exposure to trauma and torture. Data were described by absolute and relative frequencies, means and through regression analyses. Results: The majority of asylum seekers were male (58.6%) of Middle Eastern origin with a mean age of 33.6 years (SD = 12.1). More than half (60.1%) of the participants had one or more physical health complaints, whereas mental health complaints were less frequent (25.0%). Asylum seekers, who had been exposed to trauma were more likely to have physical health complaints (OR 1.52, 95% CI 1.22;1.89) and to have symptoms of mental health problems (OR 12.71, 95% CI 8.76;18.45). These complaints were substantially elevated for survivors of torture. Conclusions: This relatively high prevalence of health complaints, both physical and mental, emphasises the necessity of providing appropriate and timely health care from the very beginning of the asylum process.
Protein percentage or amino acid profile: which is more important in weight loss diets?

As studies in nutrition advance, energy balance becomes increasingly simple. Previously, it was believed that a negative energy balance was sufficient for weight loss, but at present the importance of macronutrient distribution for metabolic health is being highlighted. Carbohydrate, lipid and protein have different effects on the organism, and it is established that protein is much more thermogenic than carbohydrate and fat. For the most part, the data suggest that having a higher percentage of the diet as protein (25–30%) might result in greater fat loss relative to fat-free mass loss than lower-protein diets. For example, based on a 3000 kcal day−1 diet and that protein has a thermic effect that is 20% of the energy ingested, the fat has a thermic effect of only 2% of energy intake. In relationship to carbohydrate, the thermic effect of protein is 50–100% higher, which is normally attributed to the metabolic cost of the synthesis of binding peptides, ureagenesis and gluconeogenesis (Lambert et al., 2004). In this context, the brilliant research of Flores et al. (2022) provides a new perspective on the topic. These researchers demonstrate that reducing dietary levels of histidine by 67% reduces weight gain in young, lean male mice and reduces both the fat mass and the lean mass, without altering glucose metabolism. In obese mice, the same treatment reverses diet-induced obesity and hepatic steatosis, increasing insulin sensitivity. These data are associated with increased energy expenditure. In addition, the protein restriction increases lifespan and helps to decrease the possibility of developing diabetes. In old mice, histidine restriction beginning in middle age promotes thinness and glucose tolerance. Thus, it seems that in addition to the percentage of protein of the diet, the amino acid profile is also important. In their study, Flores et al. (2022) argue that the beneficial effects of low-protein diets might be attributable to reduced consumption of essential amino acids. In this context, branched-chain amino acids, namely leucine, isoleucine and valine, have been linked to obesity and insulin-resistant diabetes. This restriction provoked glycaemic and body weight control. These findings were also researched and addressed in another excellent article published in The Journal of Physiology, written by Cummings et al. (2018), wherein it is reported that the reduction of branched-chain amino acid levels in the diet causes a reversal of obesity (slowing fat mass gain) and metabolic dysfunction, besides contributing to better regulation of blood glucose and insulin sensitivity. Branched-chain amino acids promote persistent activation of serine kinase S6K1
Failure of the Hill determinant method for the sextic anharmonic oscillator

An extended analysis of eigenvalues and wavefunctions resulting from the Hill determinant method is carried out for the one-dimensional sextic anharmonic oscillator. It is shown that, in spite of a seemingly natural ansatz of the method, irrelevant wavefunctions may appear, leading to incorrect eigenvalues. The domain of applicability of the method is limited and its practical use demands a priori investigation before concrete calculations of spectral characteristics. Effective variational calculations based on adequate trial functions are performed and comparison of the results of both approaches is presented.
DMT-EV: An Explainable Deep Network for Dimension Reduction

Dimension reduction (DR) is commonly utilized to capture the intrinsic structure and transform high-dimensional data into low-dimensional space while retaining meaningful properties of the original data. It is used in various applications, such as image recognition, single-cell sequencing analysis, and biomarker discovery. However, contemporary parametric-free and parametric DR techniques suffer from several significant shortcomings, such as the inability to preserve global and local features and the poor generalisation performance. On the other hand, regarding explainability, it is crucial to comprehend the embedding process, especially the contribution of each part to the embedding process, while understanding how each feature affects the embedding results that identify critical components and help diagnose the embedding process. To address these problems, we have developed a deep neural network method called DMT-EV, which provides not only excellent performance in structural maintainability but also explainability to the DR therein. DMT-EV starts with data augmentation and a manifold-based loss function to improve embedding performance. The explanation is based on saliency maps and aims to examine the trained DMT-EV parameters and contributions of components during the embedding process. The proposed techniques are integrated with a visual interface to help the user to adjust DMT-EV to achieve better DR performance and explainability. The interactive visual interface makes it easier to illustrate the data features, compare different DR techniques, and investigate DR. An in-depth experimental comparison shows that DMT-EV consistently outperforms the state-of-the-art methods in both performance measures and explainability.
Efficacy and Safety of Clopidogrel Versus Ticagrelor for Stabilized Patients With Acute Coronary Syndromes After Percutaneous Coronary Intervention: Results From a Real-World Registry in China

Background: The first 3 months after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS) is a high-risk period for adverse events, including ischemic and bleeding events, which decrease greatly with time. It is worth investigating whether the use of potent P2Y12 inhibitors is necessary after the early stage. The purpose of this study was to investigate the differences in clinical outcomes between clopidogrel and ticagrelor in stable patients without ischemic or major bleeding events during the first 3 months after PCI. Methods: Data for this study were obtained from the PHARM-ACS registry (NCT04184583). Patients who were free from ischemic and major bleeding events in the first 3 months after PCI were enrolled. Inverse probability of treatment weighting (IPTW) and Cox proportional hazards model were applied to compare the differences in clinical outcomes between the 2 groups. Major adverse cardiovascular and cerebrovascular events (MACCE) were considered the primary end point, and major bleeding was considered the secondary end point. Results: A total of 6662 patients were included in this study. Of these, 3465 were treated with clopidogrel plus aspirin (clopidogrel group) and 3197 with ticagrelor plus aspirin (ticagrelor group). There were no significant differences in MACCE after IPTW adjustment for baseline variables (IPTW-adjusted HR, 1.06; 95% CI, 0.90–1.25) or major bleeding events (IPTW-adjusted HR, 0.97; 95% CI, 0.67–1.41) between the 2 groups. However, the incidence of minor bleeding in the clopidogrel group was significantly lower than that in the ticagrelor group (IPTW-adjusted HR, 0.65; 95% CI, 0.59–0.71). Conclusion: In patients with ACS who were free from ischemic or major bleeding events during the first 3 months after PCI, the subsequent clopidogrel treatment might reduce minor bleeding events without increasing the risk of MACCE compared with ticagrelor. However, the results still need to be confirmed by large randomized controlled studies in the future.
Genetically engineered multicistronic allele of Pmel yielding highly specific CreERT2‐mediated recombination in the melanocyte lineage

Genetic approaches that allow lineage tracing are essential to our future understanding of melanocytes and melanoma. To date, the approaches used to label melanocytes in mice have relied on random integration of transgenes driven by the promoters of the Tyrosinase and Dopachrome tautomerase genes, knock‐in to the Dopachrome tautomerase locus or knock‐in to the Mlana locus in a bacterial artificial chromosome. These strategies result in expression in other tissues such as telencephalon and other cell types such as nerves. Here we used homologous recombination in mouse embryonic stem cells to generate a targeted multicistronic allele of the Pmel locus that drives melanocyte‐specific expression of CreERT2, nuclear localised H2B‐Cerulean and membrane localised marcks‐mKate2 allowing live imaging of melanocytes and activation of other conditional alleles. We combined this allele with R26R‐EYFP mice allowing induction of EYFP expression on administration of tamoxifen or its metabolite 4‐OHT. The fluorescent proteins H2B‐Cerulean and marcks‐mKate2 label the cell nucleus and plasma membrane respectively allowing live imaging and FACS isolation of melanoblasts and melanocytes as well as serving to provide an internal control allowing estimation of recombination efficiency after administration of tamoxifen. We demonstrate the utility of the transgene in embryonic and adult tissues.
Microstructural and electrical properties of BaTiO3 epitaxial films on SrTiO3 substructures with a LaNiO3 conductive layer as a template

BaTiO3 (BTO) films have been epitaxially grown on SrTiO3(001) and SrTiO3(111) substrates with a LaNiO3 conductive layer as a template using pulsed laser deposition. X-ray diffraction θ–2θ and ψ scanning reveal that the epitaxial relationship for these samples fabricated at 600 °C and 700 °C are BTO[001]//LNO[001]//STO[001] and BTO[111]//LNO[111]//STO[111], respectively. Ex situ reflective high energy electron diffraction patterns also clearly confirm this epitaxial relationship. The epitaxial growth can be more easily realized on LNO-inserted STO(001) substrates at a relatively wide range of temperatures. From C–V measurements, the dielectric constant of the epitaxial (001)BTO film is determined as 159.5, which is larger than the value 89.6 of (111)BTO film. The remanent polarization (2Pr) of the epitaxial BTO(001) thin film on the LNO-coated (001)STO substrate is 39.8 µC cm−2, which is much larger than that of the BTO(111) film on the LNO-coated STO(111) substrate. The result is also consistent with the direct observation made by piezoresponse force microscopy investigation. Thus, with the epitaxial LNO electrode template layers, the epitaxial BaTiO3(001) ferroelectric films exhibit high-quality structure and good electrical properties.
Treatment Patterns in Patients with Uterine Fibroids With and Without a Diagnosis of Heavy Menstrual Bleeding: Results from a Large U.S. Claims Database

Background: This retrospective database analysis describes clinical characteristics and treatment patterns of U.S. women with a diagnosis for uterine fibroids (UF), both with and without heavy menstrual bleeding (HMB). Materials and Methods: Two cohorts aged 18–50 years with an incident UF diagnosis, comprising women with and without claims for HMB (UF-HMB and UF-only), were identified from the IQVIA PharMetrics® Plus database (January 1, 2010–December 31, 2019). The index date was the first UF claim following diagnosis; treatment patterns were documented for postindex years 1 and 2 and the full duration of postindex follow-up. Also identified were claims for symptoms or signs potentially associated with UF. Outcomes were the proportion of patients treated with pharmacologic therapies of interest and gynecologic procedures. Logistic regression was used to identify factors associated with postdiagnosis hysterectomy and hormonal therapy. Results: A total of 66,313 (71.8%) women were included in the UF-HMB cohort (mean age [standard deviation]) 42.6 [5.4] years), and 26,068 (28.2%) in the UF-only cohort (41.8 [6.3]). Median follow-up was ∼4 years. Pain was the most common symptom (42.7% in patients with UF-HMB and 36.6% with UF-only); also common were abnormal bleeding (15.6%, 11.5%) and fatigue (22.2%, 15.5%). Within 1 year of UF diagnosis, 28.8% and 49.2% of women with UF-HMB and UF-only, respectively, had no claims for relevant pharmacologic or surgical treatment. In logistic regression, multiple factors were associated with a higher likelihood of receiving hysterectomy or hormonal therapy. Conclusions: Patients with UF-HMB were more likely to receive UF treatment, either surgical or pharmacologic, than women with UF-only. Apart from HMB, pain was the most commonly documented symptom of UF.
THE BEHAVIOR OF TOTAL LIGHTNING ACTMTY IN SEVERE FLORIDA THUNDERSTORMS

The development of a new observational system called LISDAD (Lightning Imaging Sensor Demonstration and Display) has enabled a study of severe weather in central Florida. The total flash rates for storms verified to be severe are found to exceed 60 flashes/rain, with some values reaching 500 flashes/min. Similar to earlier results for thunderstorm microbursts, the peak flash rate precedes the severe weather at the ground by 5-20 minutes. A distinguishing feature of severe storms is the presence of lightning "jumps"-abrupt increases in flash rate in advance of the maximum rate for the storm. The systematic total lightning precursor to severe weather of all kinds-wind, hail, tornadoes-is interpreted in terms of the updraft that sows the seeds aloft for severe weather at the surface and simultaneously stimulates the ice microphysics that drives the intracloud lightning activity.