Miracle-dz/UniFAR-FTUs huggingface dataset:
Preoperative Screening for Obstructive Sleep Apnea Prior to Endoscopic Skull Base Surgery: A Survey of the North American Skull Base Society

Background Obstructive sleep apnea (OSA) is a commonly seen comorbidity in patients undergoing endoscopic skull base surgery and its presence may influence perioperative decision-making. Current practice patterns for preoperative screening of OSA are poorly understood. Objective The objective of this study was to assess how endoscopic skull base surgeons screen for OSA, and how knowledge of OSA affects perioperative decision-making. Methods Seven question survey distributed to members of the North American Skull Base Society. Results Eighty-eight responses (10% response rate) were received. 60% of respondents were from academic centers who personally performed >50 cases per year. Most respondents noted that preoperative knowledge of OSA and its severity affected postoperative care and increased their concern for complications. Half of respondents noted that preoperative knowledge of OSA and its severity affects intraoperative skull base reconstruction decision-making. 70% of respondents did not have a preoperative OSA screening protocol. Body mass index and patient history were most frequently used by those who screened. Validated screening questionnaires were rarely used. 76% of respondents agreed or somewhat agreed that a preoperative polysomnogram should ideally be performed for patients with suspected OSA; however, 50% of respondents reported that <20% of their patients with suspected OSA are advised to obtain a preoperative polysomnogram. Conclusion This study reveals that most endoscopic skull base surgeons agree that OSA affects postoperative patient care, but only a minority have a preoperative screening protocol in place. Additional study is needed to assess the most appropriate screening methods and protocols for OSA patients undergoing endoscopic skull base surgery.
Myocardial Scar and Mortality in Chronic Aortic Regurgitation

Background Chronic aortic regurgitation (AR) can be associated with myocardial scarring. It is unknown if scarring in AR is linked to poor outcomes and whether aortic valve replacement impacts this association. We investigated the relationship of myocardial scarring to mortality in chronic AR using cardiac magnetic resonance. Methods and Results We enrolled patients with moderate or greater AR between 2009 and 2019 and performed a blinded assessment of left ventricle remodeling, AR severity, and presence and extent of myocardial scarring by late gadolinium enhancement. The primary outcome was all‐cause mortality. We followed 392 patients (median age 62 [interquartile range, 51–71] years), and 78.1% were men, and 25.8% had bicuspid valves. Median aortic valve regurgitant volume was 39 mL (interquartile range, 30–60). Myocardial scar was present in 131 (33.4%) patients. Aortic valve replacement was performed in 165 (49.1%) patients. During follow‐up, up to 10.8 years (median 32.3 months [interquartile range, 9.8–69.5]), 51 patients (13%) died. Presence of myocardial scar (hazard ratio [HR], 3.62; 95% CI, 2.06–6.36; P<0.001), infarction scar (HR, 4.94; 95% CI, 2.58–9.48; P<0.001), and noninfarction scar (HR, 2.75; 95% CI, 1.39–5.44; P<0.004) were associated with mortality. In multivariable analysis, the presence of scar remained independently associated with death (HR, 2.53; 95% CI, 1.15–5.57; P=0.02). Among patients with myocardial scar, aortic valve replacement was independently associated with a lower risk of mortality (HR, 0.34; 95% CI, 0.12–0.97; P=0.03), even after adjustment for confounders. Conclusions In aortic regurgitation, myocardial scar is independently associated with a 2.5‐fold increase risk in mortality. Aortic valve replacement was associated with a reduction in risk of mortality in patients with scarring.
Zebrafish Posterior Lateral Line primordium migration requires interactions between a superficial sheath of motile cells and the skin

The Zebrafish Posterior Lateral Line primordium migrates in a channel between the skin and somites. Its migration depends on the coordinated movement of its mesenchymal-like leading cells and trailing cells, which form epithelial rosettes, or protoneuromasts. We describe a superficial population of flat primordium cells that wrap around deeper epithelialized cells and extend polarized lamellipodia to migrate apposed to the overlying skin. Polarization of lamellipodia extended by both superficial and deeper protoneuromast-forming cells depends on Fgf signaling. Removal of the overlying skin has similar effects on superficial and deep cells: lamellipodia are lost, blebs appear instead, and collective migration fails. When skinned embryos are embedded in Matrigel, basal and superficial lamellipodia are recovered; however, only the directionality of basal protrusions is recovered, and migration is not rescued. These observations support a key role played by superficial primordium cells and the skin in directed migration of the Posterior Lateral Line primordium.
A pilot study demonstrating the identification of Trypanosoma brucei gambiense and T. b. rhodesiense in vectors using a multiplexed high-resolution melt qPCR

Human African Trypanosomiasis (HAT) is a potentially fatal parasitic infection caused by the trypanosome sub-species Trypanosoma brucei gambiense and T. b. rhodesiense transmitted by tsetse flies. Currently, global HAT case numbers are reaching less than 1 case per 10,000 people in many disease foci. As such, there is a need for simple screening tools and strategies to replace active screening of the human population which can be maintained post-elimination for Gambian HAT and long-term for Rhodesian HAT. Here, we describe the proof of principle application of a novel high-resolution melt assay for the xenomonitoring of Trypanosoma brucei gambiense and T. b. rhodesiense in tsetse. Both novel and previously described primers which target species-specific single copy genes were used as part of a multiplex qPCR. An additional primer set was included in the multiplex to determine if samples had sufficient genomic material for detecting genes present in low copy number. The assay was evaluated on 96 wild-caught tsetse previously identified to be positive for T. brucei s. l. of which two were known to be positive for T. b. rhodesiense. The assay was found to be highly specific with no cross-reactivity with non-target trypanosome species and the assay limit of detection was 104 tryps/mL. The qPCR successfully identified three T. b. rhodesiense positive flies, in agreement with the reference species-specific PCRs. This assay provides an alternative to running multiple PCRs when screening for pathogenic sub-species of T. brucei s. l. and produces results in less than 2 hours, avoiding gel electrophoresis and subjective analysis. This method could provide a component of a simple and efficient method of screening large numbers of tsetse flies in known HAT foci or in areas at risk of recrudescence or threatened by the changing distribution of both forms of HAT.
Experiencing social connection: A qualitative study of mothers of nonspeaking autistic children

Autistic children do not consistently show conventional signs of social engagement, which some have interpreted to mean that they are not interested in connecting with other people. If someone does not act like they are interested in connecting with you, it may make it difficult to feel connected to them. And yet, some parents report feeling strongly connected to their autistic children. We conducted phenomenological interviews with 13 mothers to understand how they experienced connection with their 5- to 14-year-old nonspeaking autistic children. Mothers of nonspeaking autistic children represent a unique group in which to study connection because their children both may not seem interested in connecting with them and have limited ability to communicate effectively using speech, a common way people connect with each other. The mothers in this study interpreted a range of child behaviors—some unconventional, but many conventional—as signs that their children were interested in connecting with them, (re)framed child behaviors that could undermine connection as caused by factors unrelated to the relationship, and expressed several convictions that may help build and sustain connection in the face of uncertainty about the meaning of their children’s behavior. Even though their autistic children may not consistently act in conventional socially oriented ways, these mothers reported perceiving their children’s behavior as embedded within an emotionally reciprocal relationship.
A survey of research quality in core facilities

Core facilities are an effective way of making expensive experimental equipment available to a large number of researchers, and are thus well placed to contribute to efforts to promote good research practices. Here we report the results of a survey that asked core facilities in Europe about their approaches to the promotion of good research practices, and about their interactions with users from the first contact to the publication of the results. Based on 253 responses we identified four ways that good research practices could be encouraged: (i) motivating users to follow the advice and procedures for best research practice; (ii) providing clear guidance on data-management practices; (iii) improving communication along the whole research process; and (iv) clearly defining the responsibilities of each party.
Oxidative Damage and Antioxidant Response in Frontal Cortex of Demented and Nondemented Individuals with Alzheimer's Neuropathology

Alzheimer's disease (AD) is characterized by progressive neurodegeneration in the cerebral cortex, histopathologically hallmarked by amyloid β (Aβ) extracellular plaques and intracellular neurofibrillary tangles, constituted by hyperphosphorylated tau protein. Correlation between these pathologic features and dementia has been challenged by the emergence of “nondemented with Alzheimer's neuropathology” (NDAN) individuals, cognitively intact despite displaying pathologic features of AD. The existence of these subjects suggests that some unknown mechanisms are triggered to resist Aβ-mediated detrimental events. Aβ accumulation affects mitochondrial redox balance, increasing oxidative stress status, which in turn is proposed as a primary culprit in AD pathogenesis. To clarify the relationship linking Aβ, oxidative stress, and cognitive impairment, we performed a comparative study on AD, NDAN, and aged-matched human postmortem frontal cortices of either sex. We quantitatively analyzed immunofluorescence distribution of oxidative damage markers, and of SOD2 (superoxide dismutase 2), PGC1α [peroxisome proliferator-activated receptor (PPAR) γ-coactivator 1α], PPARα, and catalase as key factors in antioxidant response, as well as the expression of miRNA-485, as a PGC1α upstream regulator. Our results confirm dramatic redox imbalance, associated with impaired antioxidant defenses in AD brain. By contrast, NDAN individuals display low oxidative damage, which is associated with high levels of scavenging systems, possibly resulting from a lack of PGC1α miRNA-485-related inhibition. Comparative analyses in neurons and astrocytes further highlighted cell-specific mechanisms to counteract redox imbalance. Overall, our data emphasize the importance of transcriptional and post-transcriptional regulation of antioxidant response in AD. This suggests that an efficient PGC1α-dependent “safety mechanism” may prevent Aβ-mediated oxidative stress, supporting neuroprotective therapies aimed at ameliorating defects in antioxidant response pathways in AD patients.
Microfluidic Microbial Bioelectrochemical Systems: An Integrated Investigation Platform for a More Fundamental Understanding of Electroactive Bacterial Biofilms

It is the ambition of many researchers to finally be able to close in on the fundamental, coupled phenomena that occur during the formation and expression of electrocatalytic activity in electroactive biofilms. It is because of this desire to understand that bioelectrochemical systems (BESs) have been miniaturized into microBES by taking advantage of the worldwide development of microfluidics. Microfluidics tools applied to bioelectrochemistry permit even more fundamental studies of interactions and coupled phenomena occurring at the microscale, thanks, in particular, to the concomitant combination of electroanalysis, spectroscopic analytical techniques and real-time microscopy that is now possible. The analytical microsystem is therefore much better suited to the monitoring, not only of electroactive biofilm formation but also of the expression and disentangling of extracellular electron transfer (EET) catalytic mechanisms. This article reviews the details of the configurations of microfluidic BESs designed for selected objectives and their microfabrication techniques. Because the aim is to manipulate microvolumes and due to the high modularity of the experimental systems, the interfacial conditions between electrodes and electrolytes are perfectly controlled in terms of physicochemistry (pH, nutrients, chemical effectors, etc.) and hydrodynamics (shear, material transport, etc.). Most of the theoretical advances have been obtained thanks to work carried out using models of electroactive bacteria monocultures, mainly to simplify biological investigation systems. However, a huge virgin field of investigation still remains to be explored by taking advantage of the capacities of microfluidic BESs regarding the complexity and interactions of mixed electroactive biofilms.
A Combined Systemic Strategy for Overcoming Cisplatin Resistance in Head and Neck Cancer: From Target Identification to Drug Discovery

Simple Summary The efficiency of cisplatin is limited by drug resistance in head–neck cancer (HNC) patients. In this study, we established a cisplatin resistance (CR) cell model, generated CR related transcriptome profiling, and combined application of bioinformatics methodology to discover a possible way to overcome CR. Analysis of the functional pathway revealed that mitotic division is a novel mechanism significantly contributing to CR. Spindle pole body component 25 (SPC25), a kinetochore protein, was overexpressed in CR cells and significantly correlated with worse HNC patient survival. The silencing of SPC25 increased cisplatin sensitivity and reduced cancer stemness property. Integration of CR transcriptome profiling and drug database discovered a natural extract compound, celastrol, possessing a potent cytotoxic effect in CR cells to reverse CR. Thus, we combined systemic strategies to demonstrated that a novel biological process (mitotic cell division), a hub gene (SPC25), and a natural compound (celastrol) as novel strategies for the treatment of refractory HNC. Abstract Cisplatin is the first-line chemotherapy agent for head and neck cancer (HNC), but its therapeutic effects are hampered by its resistance. In this study, we employed systemic strategies to overcome cisplatin resistance (CR) in HNC. CR cells derived from isogenic HNC cell lines were generated. The CR related hub genes, functional mechanisms, and the sensitizing candidates were globally investigated by transcriptomic and bioinformatic analyses. Clinically, the prognostic significance was assessed by the Kaplan–Meier method. Cellular and molecular techniques, including cell viability assay, tumorsphere formation assay, RT-qPCR, and immunoblot, were used. Results showed that these CR cells possessed highly invasive and stem-like properties. A total of 647 molecules was identified, and the mitotic division exhibited a novel functional mechanism significantly related to CR. A panel of signature molecules, MSRB3, RHEB, ULBP1, and spindle pole body component 25 (SPC25), was found to correlate with poor prognosis in HNC patients. SPC25 was further shown as a prominent molecule, which markedly suppressed cancer stemness and attenuated CR after silencing. Celastrol, a nature extract compound, was demonstrated to effectively inhibit SPC25 expression and reverse CR phenotype. In conclusion, the development of SPC25 inhibitors, such as the application of celastrol, maybe a novel strategy to sensitize cisplatin for the treatment of refractory HNC.
Electrolyzed Oxidizing Water Modulates the Immune Response in BALB/c Mice Experimentally Infected with Trypanosoma cruzi

Chagas disease is a major public health problem in Latin America. The mixed Th1/Th2 immune response is required against Trypanosoma cruzi. Electrolyzed oxidizing water (EOW) has been shown to have germicidal efficacy. The objective of this study was to evaluate the EOW effectiveness in T. cruzi-infected BALB/c mice clinically, immunologically, and histologically. The severity of the infection was assessed by parasitaemia, general health condition, mortality, mega syndromes, and histological lesions. IgG, TNF-alpha, IFN-gamma, and IL-1 beta levels were quantified. The EOW administration showed a beneficial effect on parasitaemia, general physical condition, and mortality. High levels of IgG1 at 50 days postinfection were observed. Prophylactic EOW treatment was able to induce a predominantly TH1 immune response based on an IgG2a levels increase at the late acute phase, and a 10-fold increase of IFN-gamma in whole acute phase. EOW was able to control the acute phase infection as effectively as benznidazole. Splenomegaly was caused by EOW treatment and lymphadenopathy was stimulated by T. cruzi infection in all groups. Severe tissue damage was not prevented by EOW treatments. Moderate efficacy may be due to immunomodulatory properties and not to a direct toxic effect on the parasite.
Cladodes from Nopalea cochenillifera (L.) Salm-Dyck (Cactaceae) attenuate postprandial glycaemia without markedly influencing α-glucosidase activity

Abstract Although the cladodes of Nopalea cochenillifera are used in Mexican traditional medicine to treat diabetes and various other diseases, its antihyperglycaemic properties, phenolic content, and antioxidant activity are not well documented. Thus, we determined the activity of a single dose of fresh, blended cladodes on postprandial glycaemia in rats after a starch load. We prepared a methanolic extract of N. cochenillifera cladodes and measured its phenolic content, antioxidant capacity, and α-glucosidase inhibitory activity. The antihyperglycaemic effect of blended cladodes was similar to that of acarbose when considering the changes in glucose levels from baseline. Furthermore, the methanolic extract contained a considerable amount of phenolic compounds and exhibited antioxidant activity in the DPPH assay, but did not markedly inhibit α-glucosidase and had a low antioxidant effect in the ABTS test. Graphical Abstract
Evaluating 10 Commercially Available SARS-CoV-2 Rapid Serological Tests by Use of the STARD (Standards for Reporting of Diagnostic Accuracy Studies) Method

Numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapid serological tests have been developed, but their accuracy has usually been assessed using very few samples, and rigorous comparisons between these tests are scarce. In this study, we evaluated and compared 10 commercially available SARS-CoV-2 rapid serological tests using the STARD (Standards for Reporting of Diagnostic Accuracy Studies) methodology. ABSTRACT Numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapid serological tests have been developed, but their accuracy has usually been assessed using very few samples, and rigorous comparisons between these tests are scarce. In this study, we evaluated and compared 10 commercially available SARS-CoV-2 rapid serological tests using the STARD (Standards for Reporting of Diagnostic Accuracy Studies) methodology. Two hundred fifty serum samples from 159 PCR-confirmed SARS-CoV-2 patients (collected 0 to 32 days after the onset of symptoms) were tested with rapid serological tests. Control serum samples (n = 254) were retrieved from pre-coronavirus disease (COVID) periods from patients with other coronavirus infections (n = 11), positivity for rheumatoid factors (n = 3), IgG/IgM hyperglobulinemia (n = 9), malaria (n = 5), or no documented viral infection (n = 226). All samples were tested using rapid lateral flow immunoassays (LFIAs) from 10 manufacturers. Only four tests achieved ≥98% specificity, with the specificities ranging from 75.7% to 99.2%. The sensitivities varied by the day of sample collection after the onset of symptoms, from 31.7% to 55.4% (days 0 to 9), 65.9% to 92.9% (days 10 to 14), and 81.0% to 95.2% (>14 days). Only three of the tests evaluated met French health authorities’ thresholds for SARS-CoV-2 serological tests (≥90% sensitivity and ≥98% specificity). Overall, the performances varied greatly between tests, with only one-third meeting acceptable specificity and sensitivity thresholds. Knowledge of the analytical performances of these tests will allow clinicians and, most importantly, laboratorians to use them with more confidence; could help determine the general population’s immunological status; and may help diagnose some patients with false-negative real-time reverse transcription-PCR (RT-PCR) results.
The impact of episodic screening interruption: COVID-19 and population-based cancer screening in Canada

Background Population-based cancer screening can reduce cancer burden but was interrupted temporarily due to the COVID-19 pandemic. We estimated the long-term clinical impact of breast and colorectal cancer screening interruptions in Canada using a validated mathematical model. Methods We used the OncoSim breast and colorectal cancers microsimulation models to explore scenarios of primary screening stops for 3, 6, and 12 months followed by 6–24-month transition periods of reduced screening volumes. For breast cancer, we estimated changes in cancer incidence over time, additional advanced-stage cases diagnosed, and excess cancer deaths in 2020–2029. For colorectal cancer, we estimated changes in cancer incidence over time, undiagnosed advanced adenomas and colorectal cancers in 2020, and lifetime excess cancer incidence and deaths. Results Our simulations projected a surge of cancer cases when screening resumes. For breast cancer screening, a three-month interruption could increase cases diagnosed at advanced stages (310 more) and cancer deaths (110 more) in 2020–2029. A six-month interruption could lead to 670 extra advanced cancers and 250 additional cancer deaths. For colorectal cancers, a six-month suspension of primary screening could increase cancer incidence by 2200 cases with 960 more cancer deaths over the lifetime. Longer interruptions, and reduced volumes when screening resumes, would further increase excess cancer deaths. Conclusions Interruptions in cancer screening will lead to additional cancer deaths, additional advanced cancers diagnosed, and a surge in demand for downstream resources when screening resumes. An effective strategy is needed to minimize potential harm to people who missed their screening.