Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional Genomic and Biochemical Analysis Reveals Pleiotropic Effect of Congo Red on Aspergillus fumigatus

The compound Congo red (CR) has been historically used for coloring treatment and histological examination as well to inhibit the growth of yeast and filamentous fungi. It has been thought that CR binds to β-1,3-glucans in the fungal cell wall, disrupting the organization of the cell wall structure. ABSTRACT Inhibition of fungal growth by Congo red (CR) has been putatively associated with specific binding to β-1,3-glucans, which blocks cell wall polysaccharide synthesis. In this study, we searched for transcription factors (TFs) that regulate the response to CR and interrogated their regulon. During the investigation of the susceptibility to CR of the TF mutant library, several CR-resistant and -hypersensitive mutants were discovered and further studied. Abnormal distorted swollen conidia called Quasimodo cells were seen in the presence of CR. Quasimodo cells in the resistant mutants were larger than the ones in the sensitive and parental strains; consequently, the conidia of the resistant mutants absorbed more CR than the germinating conidia of the sensitive or parental strains. Accordingly, this higher absorption rate by Quasimodo cells resulted in the removal of CR from the culture medium, allowing a subset of conidia to germinate and grow. In contrast, all resting conidia of the sensitive mutants and the parental strain were killed. This result indicated that the heterogeneity of the conidial population is essential to promote the survival of Aspergillus fumigatus in the presence of CR. Moreover, amorphous surface cell wall polysaccharides such as galactosaminogalactan control the influx of CR inside the cells and, accordingly, resistance to the drug. Finally, long-term incubation with CR led to the discovery of a new CR-induced growth effect, called drug-induced growth stimulation (DIGS), since the growth of one of them could be stimulated after recovery from CR stress. IMPORTANCE The compound Congo red (CR) has been historically used for coloring treatment and histological examination as well to inhibit the growth of yeast and filamentous fungi. It has been thought that CR binds to β-1,3-glucans in the fungal cell wall, disrupting the organization of the cell wall structure. However, other processes have been implicated in affecting CR sensitivity. Here, we explore CR susceptibility through screening a library of genetic null mutants. We find several previously uncharacterized genetic regulators important for CR susceptibility. Through biochemical and molecular characterization, we find cell membrane permeability to be important. Additionally, we characterize a novel cell type, Quasimodo cells, that occurs upon CR exposure. These cells take up CR, allowing the growth of the remaining fungi. Finally, we find that priming with CR can enhance long-term growth in one mutant.
Staff member's views and attitudes to supporting people with an Intellectual Disability: A multi-method investigation of intimate relationships and sexuality.

BACKGROUND Staff member's views and attitudes can have a significant impact on people with an intellectual disability. This study explores staff attitudes and experiences of people with an intellectual disability's expression of relationships and sexuality across service providers in Ireland. METHODS Staff (n = 86) from service providers (n = 5) completed the Attitudes to Sexuality Questionnaire-Individuals with an Intellectual Disability (ASQ-ID) and open-ended questions. RESULTS Multidirectional significant differences were noted on staff attitudes to sexuality based on demographic factors, that is, age, education, as well as non-demographics, for example, attendance at training, and active practising of religion. Qualitatively, three themes emerged: "Unsupported and Frustration"; "Taboo Subject Matter" and "Vulnerability and Access to Education". Staff reported a lack of service supports, dominant conservative cultures and people with an intellectual disability's vulnerability. CONCLUSION This study highlights the need for improved service practices and enhanced provisions for staff and the people with an intellectual disability that they support.
Digital video interventions and mental health literacy among young people: a scoping review

Abstract Background Mental health literacy is important as it relates to understanding mental illness, increasing help-seeking efficacy, and reducing mental illness-related stigma. One method to improve the mental health literacy of young people is a digital video intervention. Aims A scoping review was conducted to map existing research in the area of digital video interventions for mental health literacy among young people. Methods The scoping review was conducted following the PRISMA-ScR checklist. All results were screened based on our inclusion criteria. Results Seventeen studies were selected for analysis. In most studies (n = 14), a digital video was the only intervention whereas three studies took a multi-intervention approach. Only two of the digital video interventions were co-created with people with mental illness or university students. All studies showed positive results in favor of digital video interventions in at least one component of mental health literacy or compared to one of the comparison conditions. Conclusions Digital video interventions represent effective tools for enhancing mental health literacy. However, there is a need for active involvement of end-users in co-creation and to attend to the production quality so that the digital video intervention is as relevant, informed, and effective as possible.
Positive autoregulation of lag-1 in response to LIN-12 activation in cell fate decisions during C. elegans reproductive system development

ABSTRACT During animal development, ligand binding releases the intracellular domain of LIN-12/Notch by proteolytic cleavage to translocate to the nucleus, where it associates with the DNA-binding protein LAG-1/CSL to activate target gene transcription. We investigated the spatiotemporal regulation of LAG-1/CSL expression in Caenorhabditis elegans and observed that an increase in endogenous LAG-1 levels correlates with LIN-12/Notch activation in different cell contexts during reproductive system development. We show that this increase is via transcriptional upregulation by creating a synthetic endogenous operon, and identified an enhancer region that contains multiple LAG-1 binding sites (LBSs) embedded in a more extensively conserved high occupancy target (HOT) region. We show that these LBSs are necessary for upregulation in response to LIN-12/Notch activity, indicating that lag-1 engages in direct positive autoregulation. Deletion of the HOT region from endogenous lag-1 reduced LAG-1 levels and abrogated positive autoregulation, but did not cause hallmark cell fate transformations associated with loss of lin-12/Notch or lag-1 activity. Instead, later somatic reproductive system defects suggest that proper transcriptional regulation of lag-1 confers robustness to somatic reproductive system development. Highlighted Article: We show that lag-1 positively autoregulates during LIN-12-mediated cell fate decisions during cell fate specification via consensus LAG-1/CSL binding sites within a conserved high occupancy target sequence.
Prepectoral versus Subpectoral Tissue Expander Breast Reconstruction: A Historically Controlled, Propensity Score–Matched Comparison of Perioperative Outcomes

Background: The rising popularity of prepectoral tissue expander placement with acellular dermal matrices in immediate breast reconstruction has prompted many studies on the safety of this technique. However, a comprehensive propensity-matched, historically controlled trial comparing perioperative outcomes following prepectoral versus partial subpectoral (dual-plane) placement of tissue expanders is lacking. Methods: Retrospective propensity-matched cohort analysis was performed on all patients of two senior reconstructive surgeons who underwent bilateral tissue expander placement following a mastectomy with one of three breast surgeons at a single academic institution from 2012 onward (n = 260). Two matched groups (prepectoral and partial subpectoral) each consisted of 102 patients. Univariate and multivariable analyses were also performed to contextualize the risks associated with prepectoral reconstruction relative to demographic characteristics and other clinical factors. Results: Compared to dual-plane subpectoral placement, prepectoral placement resulted in similar rates of overall perioperative complications (32 percent versus 31 percent; p = 1.00) and perioperative complications that required operative treatment (21 percent versus 21 percent; p = 1.00). There were no significant differences between the groups in complication rates for hematomas, seromas, impaired wound healing, and infection. Although prepectoral placement was associated with prolonged time to drain removal, those patients completed the expansion process twice as fast, were expanded further in the operating room, and were more than twice as likely to forgo clinic-based expansion. Prepectoral reconstruction was not associated with increased risk for any complications in univariate or multivariable analysis. Conclusions: Prepectoral tissue expander placement permitted greater intraoperative filling of expanders and a reduced likelihood of clinic-based expansion, with no increase in adverse outcomes compared to partial subpectoral placement. Adoption of this technique may reduce unnecessary clinic visits; shorten the delay before adjuvant therapy; and minimize patient apprehension, pain, and discomfort related to clinic-based expansion. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.
Mysteries of Visual Experience

Science is a crowning glory of the human spirit and its applications remain our best hope for social progress. But there are limitations to current science and perhaps to any science. The general mind-body problem is known to be intractable and currently mysterious. This is one of many deep problems that are universally agreed to be beyond the current purview of Science, including quantum phenomena, etc. But all of these famous unsolved problems are either remote from everyday experience (entanglement, dark matter) or are hard to even define sharply (phenomenology, consciousness, etc.). An updated summary of this work has been published as: Feldman, J. (2022). Computation, perception, and mind. Behavioral and Brain Sciences, 45, E48. doi:10.1017/S0140525X21001886 A more readable, open access, version is: https://escholarship.org/uc/item/6cs78450
Furthering Productive Aging through Public-Private Sector Alliances: The Case of the Mexican Government and Starbucks Company

ABSTRACT This commentary focuses on the remunerated work dimension of productive aging in Mexico, specifically paid employment. The main purpose is to draw attention to productive aging policies and programs built on alliances between the Mexican government and private companies – e.g., Starbucks – and then to analyze the potential impacts of such alliances on the older population. We argue that although the Mexican government emphasizes the rights of older adults to engage in paid-employment programs through such alliances, it is not addressing the issues that underlie paid-employment activities in later life, such as conditions of inequality, lack of opportunities, and poverty. We also argue that the instrumentation of productive aging programs implemented by the government should consider the costs and benefits for older adults. Solid, research-based evidence is needed to better implement productive aging programs by accounting for the factors that influence older adults’ decisions to continue working, the functional capacities of older workers, and their performance needs.
Testing of four-sample pools offers resource optimization without compromising diagnostic performance of real time reverse transcriptase-PCR assay for COVID-19

Quick identification and isolation of SARS-CoV-2 infected individuals is central to managing the COVID-19 pandemic. Real time reverse transcriptase PCR (rRT-PCR) is the gold standard for COVID-19 diagnosis. However, this resource-intensive and relatively lengthy technique is not ideally suited for mass testing. While pooled testing offers substantial savings in cost and time, the size of the optimum pool that offers complete concordance with results of individualized testing remains elusive. To determine the optimum pool size, we first evaluated the utility of pool testing using simulated 5-sample pools with varying proportions of positive and negative samples. We observed that 5-sample pool testing resulted in false negativity rate of 5% when the pools contained one positive sample. We then examined the diagnostic performance of 4-sample pools in the operational setting of a diagnostic laboratory using 500 consecutive samples in 125 pools. With background prevalence of 2.4%, this 4-sample pool testing showed 100% concordance with individualized testing and resulted in 66% and 59% reduction in resource and turnaround time, respectively. Since the negative predictive value of a diagnostic test varies inversely with prevalence, we re-tested the 4-sample pooling strategy using a fresh batch of 500 samples in 125 pools when the prevalence rose to 12.7% and recorded 100% concordance and reduction in cost and turnaround time by 36% and 30%, respectively. These observations led us to conclude that 4-sample pool testing offers the optimal blend of resource optimization and diagnostic performance across difference disease prevalence settings.
Modulation of doping and biaxial strain on the transition temperature of the charge density wave transition in 1T-TiSe2

We study the effects of charge doping and biaxial strains on the transition temperature of charge density wave (CDW) transition in TiSe2. We find soft phonon modes at the M and L points in the Brillouin zone of TiSe2, and a 0.043 eV Fermi–Dirac smearing width can suppress these soft modes. In this way, the transition temperature of CDW is quantitatively represented by the smearing width. After doping with electrons or holes, we find that the critical smearing widths to eliminate the CDW transition both decrease, indicating the same suppression effect on the CDW transition of electron doping and hole doping. Comparatively, only compressive biaxial strains can lower down the transition temperature of CDW transition in TiSe2, while stretching strains enlarges the transition temperature.
Updated Diagnostic Criteria for Paraneoplastic Neurologic Syndromes

Objective The contemporary diagnosis of paraneoplastic neurologic syndromes (PNSs) requires an increasing understanding of their clinical, immunologic, and oncologic heterogeneity. The 2004 PNS criteria are partially outdated due to advances in PNS research in the last 16 years leading to the identification of new phenotypes and antibodies that have transformed the diagnostic approach to PNS. Here, we propose updated diagnostic criteria for PNS. Methods A panel of experts developed by consensus a modified set of diagnostic PNS criteria for clinical decision making and research purposes. The panel reappraised the 2004 criteria alongside new knowledge on PNS obtained from published and unpublished data generated by the different laboratories involved in the project. Results The panel proposed to substitute “classical syndromes” with the term “high-risk phenotypes” for cancer and introduce the concept of “intermediate-risk phenotypes. ” The term “onconeural antibody” was replaced by “high risk” (>70% associated with cancer) and “intermediate risk” (30%–70% associated with cancer) antibodies. The panel classified 3 levels of evidence for PNS: definite, probable, and possible. Each level can be reached by using the PNS-Care Score, which combines clinical phenotype, antibody type, the presence or absence of cancer, and time of follow-up. With the exception of opsoclonus-myoclonus, the diagnosis of definite PNS requires the presence of high- or intermediate-risk antibodies. Specific recommendations for similar syndromes triggered by immune checkpoint inhibitors are also provided. Conclusions The proposed criteria and recommendations should be used to enhance the clinical care of patients with PNS and to encourage standardization of research initiatives addressing PNS.
Neurophysiological aspects of isotonic exercises in temporomandibular joint dysfunction syndrome.

PURPOSE The aim of the study was to investigate the electroneurophysiological aspects of volunteers with temporomandibular disorders before and after performing isotonic exercises for pain relief and self-care guidelines. METHODS The study was a parallel controlled randomized controlled trial under protocol 1,680,920. The inclusion criteria were age between 18 and 60 years, muscle temporomandibular dysfunction with or without limitation of mouth opening and self-reported pain with scores between 4 and 10. The individuals were randomized into experimental group and control. Twenty-three volunteers participated in the study, most of then were female. Control group had 11 and experimental group 12 individuals. Dropouts occurred in both groups, two in the experimental group and three in the control group. Since there were an intergroup imbalance the power density was analysed just in experimental group. Electroencephalographic recording was performed before and after the interventions, using the 32-channel apparatus, with sample frequency of 600 Hz and impedance of 5 kΩ. The data were processed through the MATLAB computer program. The individual records filtered off-line, using bandpass between 0.5 and 50 Hz. Epochs of 1,710 ms were created and the calculation of the absolute power density calculated by means of the fast Fourier transform. The statistical approach was inferential and quantitative. RESULTS The alpha power density analyzed presented a difference, but not significant, when compared in the two moments. CONCLUSION According to this study, isotonic exercises performed to reduce pain provided a small increase in alpha power density in the left temporal, parietal and occipital regions.
Thin film synthesis and characterization of a chemically ordered magnetic nanolaminate (V,Mn)3GaC2

We report on synthesis and characterization of a new magnetic nanolaminate (V,Mn)3GaC2, which is the first magnetic MAX phase of a 312 stoichiometry. Atomically resolved energy dispersive X-ray mapping of epitaxial thin films reveals a tendency of alternate chemical ordering between V and Mn, with atomic layers composed of primarily one element only. Magnetometry measurements reveal a ferromagnetic response between 50 K and 300 K, with indication of a magnetic ordering temperature well above room temperature.
Testing the extreme male brain hypothesis: Is autism spectrum disorder associated with a more male‐typical brain?

Autism spectrum disorder (ASD) is more common in males than females and has been linked to male‐typical behavior. Accordingly, the “Extreme Male Brain” hypothesis suggests that ASD is associated with an exaggeratedly male‐typical brain. To test this hypothesis, we derived a data‐driven measure of individual differences along a male–female dimension based on sex differences in subcortical brain shape (i.e., brain maleness) by training our algorithm on two population samples (Queensland Twin IMaging study and Human Connectome Project; combined N = 2153). We then applied this algorithm to two clinical datasets (Autism Brain Imaging Data Exchange I and II; ASD N = 1060; neurotypical controls N = 1166) to obtain a brain maleness score for each individual, representing maleness of their brain on a male–female continuum. Consistent with the Extreme Male Brain hypothesis, we found a higher mean brain maleness score in the ASD group than in controls (d = 0.20 [0.12–0.29]), parallel to higher scores for control males than control females (d = 1.17 [1.05–1.29]). Further, brain maleness was positively associated with autistic symptoms. We tested the possibility this finding was driven by the ASD group's larger brains than controls (d = 0.17 [0.08–0.25]), given that males had larger brains than females (d = 0.96 [0.84–1.07]). Indeed, after adjusting for differences in brain size, the brain maleness difference between the ASD group and controls disappeared, and no association with autistic symptoms remained (after controlling for multiple comparisons), suggesting greater maleness of the autistic brain is driven by brain size. Brain maleness may be influenced by the same factors that influence brain size.
A collection of genetic mouse lines and related tools for inducible and reversible intersectional mis-expression

ABSTRACT Thanks to many advances in genetic manipulation, mouse models have become very powerful in their ability to interrogate biological processes. In order to precisely target expression of a gene of interest to particular cell types, intersectional genetic approaches using two promoter/enhancers unique to a cell type are ideal. Within these methodologies, variants that add temporal control of gene expression are the most powerful. We describe the development, validation and application of an intersectional approach that involves three transgenes, requiring the intersection of two promoter/enhancers to target gene expression to precise cell types. Furthermore, the approach uses available lines expressing tTA/rTA to control the timing of gene expression based on whether doxycycline is absent or present, respectively. We also show that the approach can be extended to other animal models, using chicken embryos. We generated three mouse lines targeted at the Tigre (Igs7) locus with TRE-loxP-tdTomato-loxP upstream of three genes (p21, DTA and Ctgf), and combined them with Cre and tTA/rtTA lines that target expression to the cerebellum and limbs. Our tools will facilitate unraveling biological questions in multiple fields and organisms. Summary: This study presents a collection of four mouse lines and genetic tools for mis-expression-mediated manipulation of cellular activity with high spatiotemporal control, in a reversible manner.
Cost Analysis of Open Surgical Bedside Tracheostomy in Intensive Care Unit Patients

Objectives: Open surgical tracheostomy (OST) is a common procedure performed on intensive care unit (ICU) patients. The procedure can be performed bedside in the ICU (bedside open surgical tracheostomy, BeOST) or in the operating room (operating room open surgical tracheostomy, OROST), with comparable safety and long-term complication rates. We aimed to perform a cost analysis and evaluate the use of human resources and the total time used for both BeOSTs and OROSTs. Methods: All OSTs performed in 2017 at 5 different ICUs at Oslo University Hospital Ullevål were retrospectively evaluated. The salaries of the personnel involved in the 2 procedures were obtained from the hospital’s finance department. The time taken and the number of procedures performed were extracted from annual reports and from the electronic patient record system, and the annual expenditures were calculated. Results: Altogether, 142 OSTs were performed, of which 122 (86%) and 20 (14%) were BeOSTs and OROSTs, respectively. A BeOST cost 343 EUR (95% CI: 241.4-444.6) less than an OROST. Bedside open surgical tracheostomies resulted in an annual cost efficiency of 41.818 EUR. In addition, BeOSTs freed 279 hours of operating room occupancy during the study year. Choosing BeOST instead of OROST made 1 nurse, 2 surgical nurses, and 1 anesthetic nurse redundant. Conclusion: Bedside open surgical tracheostomy appears to be cost-, time-, and resource-effective than OROST. In the absence of contraindications, BeOSTs should be performed in ICU patients whenever possible.