Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of Oscillation Structures on Inertial-Range Intermittence and Topology in Turbulent Field

Using the incompressible isotropic turbulent fields obtained from direct numerical simulation and large-eddy simulation, we studied the statistics of oscillation structures based on local zero-crossings and their relation with inertial-range intermittency for transverse velocity and passive scalar. Our results show that for both the velocity and passive scalar, the local oscillation structures are statistically scale-invariant at high Reynolds number, and the inertial-range intermittency of the overall flow region is determined by the most intermittent structures characterized by one local zero-crossing. Local flow patterns conditioned on the oscillation structures are characterized by the joint probability density function of the invariants of the filtered velocity gradient tensor at inertial range. We demonstrate that the most intermittent regions for longitudinal velocity tend to lay at the saddle area, while those for the transverse velocity tend to locate at the vortex-dominated area. The connection between the ramp-cliff structures in passive scalar field and the corresponding saddle regions in the velocity field is also verified by the approach of oscillation structure classification.
The Phosphatase Cascade Nem1/Spo7-Pah1 Regulates Fungal Development, Lipid Homeostasis, and Virulence in Botryosphaeria dothidea

Botryosphaeria canker and fruit rot caused by the fungus Botryosphaeria dothidea is one of the most destructive diseases of apple worldwide. Our data indicated that the phosphatase cascade Nem1/Spo7-Pah1 plays important roles in the regulation of fungal growth, development, lipid homeostasis, environmental stress responses, and virulence in B. dothidea. ABSTRACT Protein phosphatase complex Nem1/Spo7 plays crucial roles in the regulation of various biological processes in eukaryotes. However, its biological functions in phytopathogenic fungi are not well understood. In this study, genome-wide transcriptional profiling analysis revealed that Nem1 was significantly upregulated during the infection process of Botryosphaeria dothidea, and we identified and characterized the phosphatase complex Nem1/Spo7 and its substrate Pah1 (a phosphatidic acid phosphatase) in B. dothidea. Nem1/Spo7 physically interacted with and dephosphorylated Pah1 to promote triacylglycerol (TAG) and subsequent lipid droplet (LD) synthesis. Moreover, the Nem1/Spo7-dependently dephosphorylated Pah1 functioned as a transcriptional repressor of the key nuclear membrane biosynthesis genes to regulate nuclear membrane morphology. In addition, phenotypic analyses showed that the phosphatase cascade Nem1/Spo7-Pah1 was involved in regulating mycelial growth, asexual development, stress responses, and virulence of B. dothidea. IMPORTANCE Botryosphaeria canker and fruit rot caused by the fungus Botryosphaeria dothidea is one of the most destructive diseases of apple worldwide. Our data indicated that the phosphatase cascade Nem1/Spo7-Pah1 plays important roles in the regulation of fungal growth, development, lipid homeostasis, environmental stress responses, and virulence in B. dothidea. The findings will contribute to the in-depth and comprehensive understanding of Nem1/Spo7-Pah1 in fungi and the development of target-based fungicides for disease management.
MiR-431 attenuates synaptic plasticity and memory deficits in APPswe/PS1dE9 mice

Synaptic plasticity impairment plays a critical role in the pathogenesis of Alzheimer’s disease (AD), and emerging evidence has shown that microRNAs (miRs) are alternative biomarkers and therapeutic targets for synaptic dysfunctions in AD. In this study, we found that the level of miR-431 was downregulated in the plasma of patients with amnestic mild cognitive impairment and AD. In addition, it was decreased in the hippocampus and plasma of APPswe/PS1dE9 (APP/PS1) mice. Lentivirus-mediated miR-431 overexpression in the hippocampus CA1 ameliorated synaptic plasticity and memory deficits of APP/PS1 mice, while it did not affect amyloid-β levels. Smad4 was identified as a target of miR-431, and Smad4 knockdown modulated the expression of synaptic proteins, including SAP102, and protected against synaptic plasticity and memory dysfunctions in APP/PS1 mice. Furthermore, Smad4 overexpression reversed the protective effects of miR-431, indicating that miR-431 attenuated synaptic impairment at least partially by Smad4 inhibition. Thus, these results indicated that miR-431/Smad4 might be a potential therapeutic target for AD treatment.
On the breaking of internal solitary waves at a ridge

An experimental laboratory study has been carried out to investigate the propagation of an internal solitary wave of depression and its distortion by a bottom ridge in a two-layer stratified fluid system. Wave profiles, density fields and velocity fields have been measured at three reference locations, namely upstream, downstream and over the ridge. Experiments have been performed with wave amplitudes in the range 0.2– 1.9 times the depth of the upper layer, and a ratio between the lower and the upper layer in the range 3.0–8.5. The ridge slope was varied from 0.1 to 0.33 and the maximum ridge height was two-thirds of the thicker fluid layer. Over the ridge, the flow has been classified into: (i) cases when the bottom ridge has little influence on the propagation and spatial structure of the internal solitary wave, (ii) cases where the internal solitary wave is significantly distorted by the blocking effect of the ridge (though no wave breaking occurs), and (iii) cases for which the internal solitary wave is broken as it encounters and passes over the bottom ridge. A detailed description of the processes leading to wave breaking is given. Breaking has been found to take place when the fluid velocity in the lower layer exceeds 0.7 of a local nonlinear wave speed, defined at the top of the ridge. The breaking condition is also expressed in terms of the amplitude of the incident wave, the layer thickness ratio and the relative height of the ridge. The wave breaking can be determined from the input parameters of the experiment. The transmitted waves have been found to always consist of a leading pulse (solitary wave) followed by a dispersive wavetrain. The (solitary) wave amplitude is significantly reduced only when breaking takes place at the ridge. Internal waves of mode two are generated in cases with strong breaking.
Informed Consent and Debriefing When Deceiving Participants: A Systematic Review of Research Ethics Guidelines

Informed consent and debriefing of research participants in studies that use deception are ethical safeguards for which existing scholarly work on their implementation remains variable and insufficiently clear. A systematic review of research ethics guidelines was conducted to sketch a picture of whether, why and how informed consent and debriefing are recommended when using deception. Documents roughly agreed on several general principles, but varied significantly in the specifics of why and whether these safeguards are necessary, in which conditions and how they should be implemented. Various aspects that appear in the literature could not be found in the guidelines. In our review, guidance was integrated and showed a variation of implementation strategies that could help in contextualizing these safeguards.
Evolution, persistence, and host adaption of a gonococcal AMR plasmid that emerged in the pre-antibiotic era

Plasmids are diverse extrachromosomal elements significantly that contribute to interspecies dissemination of antimicrobial resistance (AMR) genes. However, within clinically important bacteria, plasmids can exhibit unexpected narrow host ranges, a phenomenon that has scarcely been examined. Here we show that pConj is largely restricted to the human-specific pathogen, Neisseria gonorrhoeae. pConj can confer tetracycline resistance and is central to the dissemination of other AMR plasmids. We tracked pConj evolution from the pre-antibiotic era 80 years ago to the modern day and demonstrate that, aside from limited gene acquisition and loss events, pConj is remarkably conserved. Notably, pConj has remained prevalent in gonococcal populations despite cessation of tetracycline use, thereby demonstrating pConj adaptation to its host. Equally, pConj imposes no measurable fitness costs and is stably inherited by the gonococcus. Its maintenance depends on the co-operative activity of plasmid-encoded Toxin:Antitoxin (TA) and partitioning systems rather than host factors. An orphan VapD toxin encoded on pConj forms a split TA with antitoxins expressed from an ancestral co-resident plasmid or a horizontally-acquired chromosomal island, potentially explaining pConj’s limited distribution. Finally, ciprofloxacin can induce loss of this highly stable plasmid, reflecting epidemiological evidence of transient reduction in pConj prevalence when fluoroquinolones were introduced to treat gonorrhoea.
Immunological disease activity parameters at conception are risk factors for preterm birth and low birth weight in patients with systemic lupus erythematosus

Objective This study aimed to identify which disease activity parameters may be risk factors for preterm birth (PB) and low birth weight (LBW) in patients with systemic lupus erythematosus (SLE). We also analyzed the extent to which these parameters affected PB and LBW. Methods We collected the SLE Disease Activity Index (SLEDAI), the rate of lupus low disease activity state (LLDAS) attainment, complement levels, and the titer of anti-double stranded DNA (dsDNA) antibody as disease activity parameters. We retrospectively analyzed the associations of these parameters with PB and LBW. Results Sixty pregnancies were included in this study. C3 levels and anti-dsDNA antibody titers at conception were strongly associated with PB (p = 0.03 and p = 0.01, respectively), whereas C3 and CH50 levels were associated with LBW (p = 0.02 and p = 0.03, respectively). A logistic regression analysis showed that the cutoff values of C3 and anti-dsDNA antibody for PB were 62.0 mg/dl and 5.4 IU/ml, respectively. The cutoff values of C3 and CH50 for LBW were 87.0 mg/dl and 41.8 U/ml, respectively. The risk of PB or LBW was increased when divided by the cutoff value, and the combination of these cutoff values showed a significantly higher risk of PB and LBW (p = 0.01 and p < 0.01, respectively). Conclusions PB and LBW are strongly associated with disease activity parameters in patients with SLE. Therefore, strictly monitoring and controlling these disease activity parameters, with or without clinical manifestation, is important for women who want to become mothers.
Video Calls as a Replacement for Family Visits During Lockdowns in Aged Care: Interview Study With Family Members

Background Lockdowns have been used to prevent the spread of transmissible illnesses such as influenza, norovirus, and COVID-19 in care homes. However, lockdowns deny care home residents supplemental care and the socioemotional enrichment that comes from seeing family members. Video calling has the potential to enable ongoing contact between residents and family members during lockdowns. However, video calls can be considered by some as a poor substitute for in-person visits. It is important to understand family members’ experiences with video calling during lockdowns to ensure the effective use of this technology in the future. Objective This study aimed to understand how family members use video calls to communicate with relatives living in aged care during lockdowns. We focused on experiences during the COVID-19 pandemic, which involved extensive lockdowns in aged care homes. Methods We conducted semistructured interviews with 18 adults who had been using video calls with relatives living in aged care during pandemic lockdowns. The interviews focused on how participants had been using video calls, what benefits they gained from video-based interactions, and what challenges they encountered when using the technology. We analyzed the data using the 6-phase reflexive approach to thematic analysis by Braun and Clarke. Results We developed 4 themes through our analysis. Theme 1 interprets video calling as a medium for the continuation of care during lockdowns. Using video calls, family members were able to provide social enrichment for residents and engaged in health monitoring to uphold residents’ welfare. Theme 2 highlights how video calling extended care by supporting frequent contact, transmitting nonverbal cues that were essential for communication, and negating the need for face masks. Theme 3 interprets organizational issues such as the lack of technology and staff time as impediments to the continuation of familial care through video. Finally, theme 4 highlights the need for 2-way communication, interpreting residents’ unfamiliarity with video calling and their health conditions as further barriers to the continuation of care. Conclusions This study suggests that, during restrictions arising from the COVID-19 pandemic, video calls became a medium for enabling family members to continue participating in the care of their relatives. The use of video calls to continue care illustrates their value for families during times of mandatory lockdown and supports the use of video to complement face-to-face visits at other times. However, better support is needed for video calling in aged care homes. This study also revealed a need for video calling systems that are designed for the aged care context.
Enam expression is regulated by Msx2

The precise formation of mineralized dental tissues such as enamel and/or dentin require tight transcriptional control of the secretion of matrix proteins. Here, we have investigated the transcriptional regulation of the second most prominent enamel matrix protein, enamelin, and its regulation through the major odontogenic transcription factor, MSX2.
The Quest for Reality

1. Prelude: The modern stance 2. Twilight of the gods 3. The view from Copenhagen 4. Epistemological interlude 5. Wittgenstein enters the scene 6. Shaky foundations 7. Physics interface 8. Philosophical consequences 9. Metaphysics and reality 10. Concluding epilogue
Kymriah® (tisagenlecleucel) – An overview of the clinical development journey of the first approved CAR-T therapy

ABSTRACT The emergence of cell and gene therapies has dramatically changed the treatment paradigm in oncology and other therapeutic areas. Kymriah® (tisagenlecleucel), a CD19-directed genetically modified autologous T-cell immunotherapy, is currently approved in major markets for the treatment of relapsed/refractory (r/r) pediatric and young adult acute lymphoblastic leukemia, r/r diffuse large B-cell lymphoma, and r/r follicular lymphoma. This article presents a high-level overview of the clinical development journey of tisagenlecleucel, including its efficacy outcomes and safety considerations.
Novel variants in the PAX6 gene related to isolated aniridia

Aniridia, which is a rare congenital defect of the eye, consists of iris hypoplasia or aplasia, and additional ocular abnormalities. It is most commonly caused by autosomal dominant PAX6 gene mutations. However, in about 30% of cases, it is associated with chromosomal rearrangements in the 11p13 region. The aim of this study was to identify the potential PAX6 gene variants, which could cause the isolated aniridia. Eight patients with isolated aniridia were included in this study. MLPA analysis allowed in the past to exclude large structural rearrangements of the PAX6 and adjacent genes like WT1. Blood samples were collected from the patients (and their families in familial cases) and genomic DNA was extracted from peripheral blood leukocytes and buccal cells. The amplification of the 11 exons of the PAX6 gene was performed. Bidirectional Sanger Sequencing was conducted for the identification of the potentially pathogenic variants, and for the segregation analysis of the identified variant in the family. The results were analyzed with the use of CodonCode Aligner software. In three patients, aniridia was sporadic, whereas in another five cases, the eye defect was familial. The potentially pathogenic variants in the PAX6 gene were found in 6 out of 8 patients with aniridia. We identified four known (c.781C > T, c.607C > T, and c.949C > T twice), and two novel variants (c.258_265del and c.495_496insG). Point mutations in the PAX6 gene are the most frequent cause of aniridia. The investigation of the genetic background of the disease is essential for patients to evaluate recurrence risk in the offspring.
Increased serum prolactin level may indicate more migraine attack frequency

Migraine is a common, multifactorial disorder. The exact pathomechanism of migraine remains unclear. Studies have revealed changes in serum prolactin (PRL) levels in relation to migraine, although the results have been inconsistent. The present case‐control study assessed the serum level of prolactin in migraine patients.
Dietary outcomes of community-based CVD preventive interventions: a systematic review and meta-analysis

Abstract Objective: We aimed to synthesise available evidence on the effects of community-based interventions in improving various dietary outcome measures. Design: Systematic review and meta-analysis. Setting: We searched databases including Medline, EMBASE, PSYCINFO, CINAHL and the Cochrane registry for studies reported between January 2000 and June 2022. The methodological quality of the included studies was evaluated using the Cochrane risk of bias tools for each study type. For some of the outcomes, we pooled the effect size using a random-effects meta-analysis. Participants: A total of fifty-one studies, thirty-three randomised and eighteen non-randomised, involving 100 746 participants were included. Results: Overall, thirty-seven studies found a statistically significant difference in at least one dietary outcome measure favouring the intervention group, whereas fourteen studies found no statistically significant difference. Our meta-analyses indicated that, compared with controls, interventions were effective in decreasing daily energy intake (MJ/d) (mean difference (MD): –0·25; 95 % CI: –0·37, –0·14), fat % of energy (MD: –1·01; 95 % CI: –1·76, –0·25) and saturated fat % of energy (MD: –1·54; 95 % CI: –2·01, –1·07). Furthermore, the interventions were effective in improving fibre intake (g/d) (MD: 1·08; 95 % CI: 0·39, 1·77). Effective interventions use various strategies including tailored individual lifestyle coaching, health education, health promotion activities, community engagement activities and/or structural changes. Conclusion: This review shows the potential of improving dietary patterns through community-based CVD preventive interventions. Thus, development and implementation of context-specific preventive interventions could help to minimise dietary risk factors, which in turn decrease morbidity and mortality due to CVD and other non-communicable diseases.
The Effectiveness of the Multiple-Attending-Physicians System Compared With the Single Attending-Physician System in Inpatient Setting: A Mixed-Method Study

Objectives: Medical facilities have been required to effectively utilize insufficient human resources in many countries. Therefore, we qualitatively and quantitively compared physicians’ working burden, and assessed advantages and disadvantages of the single- and the multiple-attending physicians systems in inpatient care. Methods: In this cross-sectional study, we extracted electronic health record of patients from a hospital in Japan from April 2017 to October 2018 to compare anonymous statistical data between the single-attending and multiple-attending-physicians system. Then, we conducted a questionnaire survey for all physicians of single and multiple-attending systems, asking about their physical and psychiatric workload, and their reasons and comments on their working styles. Results: The average length of hospital stay was significantly shorter in the multiple-attending system than in the single-attending system, while patients’ age, gender, and diagnoses were similar. From the questionnaire survey, no significant difference was found in all categories although physical burden in multiple-attending system tended to be lower than that in single-attending system. Advantages of multiple-attending system extracted from qualitative analysis are (1) improvement of physicians’ quality of life (QOL), (2) lifelong-learning effect, and (3) improving the quality of medical care, while disadvantages were (1) risk of miscommunications, (2) conflicting treatment policies among physicians, and (3) patients’ concern. Conclusions: The multiple-attending physician system in the inpatient setting can reduce the average length of stay for patients and also reduce the physical burden on physicians without compromising their clinical performance.
Serodominant SARS-CoV-2 Nucleocapsid Peptides Map to Unstructured Protein Regions

As SARS-CoV-2 continues to evolve, a structural and genetic understanding of key viral epitopes will be essential to the development of next-generation diagnostics and vaccines. This study uses structural biology and epitope mapping to define the antigenic regions of the viral nucleocapsid protein in sera from a cohort of COVID-19 patients with diverse clinical outcomes. ABSTRACT The SARS-CoV-2 nucleocapsid (N) protein is highly immunogenic, and anti-N antibodies are commonly used as markers for prior infection. While several studies have examined or predicted the antigenic regions of N, these have lacked consensus and structural context. Using COVID-19 patient sera to probe an overlapping peptide array, we identified six public and four private epitope regions across N, some of which are unique to this study. We further report the first deposited X-ray structure of the stable dimerization domain at 2.05 Å as similar to all other reported structures. Structural mapping revealed that most epitopes are derived from surface-exposed loops on the stable domains or from the unstructured linker regions. An antibody response to an epitope in the stable RNA binding domain was found more frequently in sera from patients requiring intensive care. Since emerging amino acid variations in N map to immunogenic peptides, N protein variation could impact detection of seroconversion for variants of concern. IMPORTANCE As SARS-CoV-2 continues to evolve, a structural and genetic understanding of key viral epitopes will be essential to the development of next-generation diagnostics and vaccines. This study uses structural biology and epitope mapping to define the antigenic regions of the viral nucleocapsid protein in sera from a cohort of COVID-19 patients with diverse clinical outcomes. These results are interpreted in the context of prior structural and epitope mapping studies as well as in the context of emergent viral variants. This report serves as a resource for synthesizing the current state of the field toward improving strategies for future diagnostic and therapeutic design.