Fact Check: Assessing the Response of ChatGPT to Alzheimer's Disease Statements with Varying Degrees of Misinformation.

Background: There are many myths regarding Alzheimer's disease (AD) that have been circulated on the Internet, each exhibiting varying degrees of accuracy, inaccuracy, and misinformation. Large language models such as ChatGPT, may be a useful tool to help assess these myths for veracity and inaccuracy. However, they can induce misinformation as well. The objective of this study is to assess ChatGPT's ability to identify and address AD myths with reliable information. Methods: We conducted a cross-sectional study of clinicians' evaluation of ChatGPT (GPT 4.0)'s responses to 20 selected AD myths. We prompted ChatGPT to express its opinion on each myth and then requested it to rephrase its explanation using a simplified language that could be more readily understood by individuals with a middle school education. We implemented a survey using Redcap to determine the degree to which clinicians agreed with the accuracy of each ChatGPT's explanation and the degree to which the simplified rewriting was readable and retained the message of the original. We also collected their explanation on any disagreement with ChatGPT's responses. We used five Likert-type scale with a score ranging from -2 to 2 to quantify clinicians' agreement in each aspect of the evaluation. Results: The clinicians (n=11) were generally satisfied with ChatGPT's explanations, with a mean (SD) score of 1.0(±0.3) across the 20 myths. While ChatGPT correctly identified that all the 20 myths were inaccurate, some clinicians disagreed with its explanations on 7 of the myths.Overall, 9 of the 11 professionals either agreed or strongly agreed that ChatGPT has the potential to provide meaningful explanations of certain myths. Conclusions: The majority of surveyed healthcare professionals acknowledged the potential value of ChatGPT in mitigating AD misinformation. However, the need for more refined and detailed explanations of the disease's mechanisms and treatments was highlighted.

Characterizing multiple sclerosis disease progression using a combined structural and functional connectivity metric.

PURPOSE: A combined resting state functional connectivity MRI (fcMRI) and diffusion tensor imaging (DTI) metric called structural and functional connectivity index (SFCI) was recently proposed for tracking disease status and progression in multiple sclerosis (MS). The metric combines fcMRI and transverse diffusivity (TD) along different functional pathways involved in principle symptomatic domains of MS. In a longitudinal study of patients with MS receiving the same MS therapy, initial worsening of transcallosal (TC) motor and frontoparietal (FP) cognitive networks, as measured by fcMRI and DTI over the first year was followed by stabilization in the second year of follow-up. In this study we have (i) probed relationships between individual and composite neurological measures of MS with SFCI and its individual components along TC motor and FP cognitive pathways and (ii) compared sensitivity of SFCI to treatment-induced longitudinal changes with each individual imaging measure. METHODS: Twenty five patients with MS (15 female, age 42 ± 8 y) participated in this study and were scanned at 3 T whole body MRI scanner with diffusion tensor imaging (DTI) and resting-state functional connectivity MRI (fcMRI) scan protocol at baseline and 6, 12, 18 and 24 months after starting fingolimod. fcMRI and TD along TC and FP pathways were combined to form structural and functional connectivity index (SFCI) at each time point. Correlations between individual/combined neurological measures and individual imaging components/SFCI at baseline and were evaluated and compared. In addition, efficacies of individual and combined imaging metrics in tracking network integrity were compared. RESULTS: Individual TD along the TC pathway was significantly inversely correlated with all individual/composite neurological scores. There were moderate correlations of TC and FP components of SFCI with most of the neurological scores, and the pathway-combined SFCI was significantly correlated with all neurological scores. Trend-level increases of both TC and FP fcMRI were observed during the second year of follow-up, both TC and FP TD increased significantly in the first year and then stabilized during the second year. A trend toward a decrease in combined imaging metrics along TC and FP were observed during the first year, followed by a trend toward an increase in these metrics during the second year, while a significant decrease in SFCI during the first year followed by a significant increase during the second year was observed. CONCLUSIONS: SFCI was more effective in tracking network integrity/disease progression than individual pathway-specific components, which supports its use as an imaging marker for MS disease status and progression.

COVID-19, Framing and Naming a Pandemic: How What Is Not in a Disease Name May Be More Important than What Is.

While the disease name and acronym COVID-19, where 'CO' refers to 'corona', 'VI' to virus, 'D' to disease, and '19' the detection year, represents a rational, historically informed, and even culturally sensitive name choice by the World Health Organization, from the perspective of an ethnography of disease framing and naming, this study finds that it does not, however, readily communicate a public health message. This observation, based on linguistic and medical anthropological research and analyses, raises a critically important question: Can or should official disease names, beyond labeling medical conditions, also be designed to function as public health messages? As the ethnography of the term COVID-19 and its 'framing' demonstrates, using acronyms for disease names in public health can not only reduce their intelligibility but may also lower emerging public perceptions of risk, inadvertently, increasing the public's vulnerability. This study argues that the ongoing messaging and communication challenges surrounding the framing of COVID-19 and its variants represent an important opportunity for public health to engage social science research on language and risk communication to critically rethink disease naming and framing and how what they are called can prefigure and inform the public's uptake of science, understandings of risk, and the perceived importance of public health guidelines.

Executive Functioning and Emotion Regulation in Children with and without ADHD.

Difficulties with emotion regulation affect the majority of youth with attention-deficit/hyperactivity disorder (ADHD) and predict greater functional impairment than ADHD symptoms alone. Deficits in executive functioning are also present for most children with ADHD, and have been linked with emotion regulation difficulties in both clinical and neurotypical populations throughout development. The current study was the first to assess all three core executive functions (working memory, inhibitory control, set shifting) simultaneously in a clinically-diverse sample of children with and without ADHD and common comorbidities and investigate the extent to which they uniquely predict emotion dysregulation. A sample of 151 children ages 8-13 years (M = 10.36, SD = 1.52; 52 girls; 70.2% White/Non-Hispanic) were assessed using a criterion battery of executive functioning tasks, teacher-reported ADHD symptoms, and parent-reported emotion regulation. Results of the bias-corrected, bootstrapped conditional effects path model revealed that better-developed working memory predicted better emotion regulation (ß = 0.23) and fewer ADHD symptoms (ß = -0.21 to -0.37), that ADHD symptoms (ß = -0.18 to -0.20) independently predicted emotion dysregulation, and that working memory exerted indirect effects on emotion regulation through both inattention and hyperactivity/impulsivity (ß = 0.04-0.07). Sensitivity analyses indicated that these effects were generally robust to control for age, sex, executive function interrelations, and inclusion/exclusion of children with co-occurring ASD. These findings underscore the importance of working memory (relative to inhibitory control and set shifting) and its relations with ADHD symptoms for understanding children's emotion regulation skills, and may help explain the limited efficacy of first-line ADHD treatments, which do not target working memory, for improving emotion regulation skills.

Furin cleavage of SARS-CoV-2 Spike promotes but is not essential for infection and cell-cell fusion.

Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infects cells by binding to the host cell receptor ACE2 and undergoing virus-host membrane fusion. Fusion is triggered by the protease TMPRSS2, which processes the viral Spike (S) protein to reveal the fusion peptide. SARS-CoV-2 has evolved a multibasic site at the S1-S2 boundary, which is thought to be cleaved by furin in order to prime S protein for TMPRSS2 processing. Here we show that CRISPR-Cas9 knockout of furin reduces, but does not prevent, the production of infectious SARS-CoV-2 virus. Comparing S processing in furin knockout cells to multibasic site mutants reveals that while loss of furin substantially reduces S1-S2 cleavage it does not prevent it. SARS-CoV-2 S protein also mediates cell-cell fusion, potentially allowing virus to spread virion-independently. We show that loss of furin in either donor or acceptor cells reduces, but does not prevent, TMPRSS2-dependent cell-cell fusion, unlike mutation of the multibasic site that completely prevents syncytia formation. Our results show that while furin promotes both SARS-CoV-2 infectivity and cell-cell spread it is not essential, suggesting furin inhibitors may reduce but not abolish viral spread.

An exploration of knowledge of students and staff at residential aged care facilities and implications for nursing education.

BACKGROUND: Advances in healthcare have contributed to population longevity with many older adults living with complex comorbidities, including those in residential aged care facilities (RACFs). Nursing staff require knowledge of gerontology, normal ageing processes and expected physiological, psychosocial, function and cognitive changes in addition to health promotion in order to provide individualised care. The complexity inherent in the medical, palliative and basic care needs of the residents makes RACFs excellent places for learning for undergraduate student nurses who undertake clinical placement as part of a Bachelor of Nursing course. Previous research has identified that knowledge of care staff is relatively poor. OBJECTIVES: To explore the knowledge and misconceptions of ageing among first year undergraduate nursing students and aged care staff facilitating a placement during a clinical learning experience. DESIGN: Descriptive cross-sectional design. SETTING: Three clinical RACFs in Australia. PARTICIPANTS: First year nursing students and staff of three different RACFs. METHOD: Pre and post-test clinical placement surveys. Students and staff completed Palmore's Facts on Ageing Quiz, a 25-item tool to assess knowledge and attitudes of ageing, before commencing the clinical placement and on the last day of a two week placement. RESULTS: Physiological questions were answered correctly. A knowledge deficit was evident from a sociological perspective. Negative attitudes have been found to devalue care and can directly affect the quality of practice in an undesirable way, forming a barrier to effective and therapeutic relationships with older adults, potentially impacting on patient care. CONCLUSIONS: From an education provider perspective, the inclusion of activities to enrich the learning activities of nurses within RACF- inclusive of reflective activities and guidance from an expert clinical facilitator - may assist in dispelling negative attitudes and stereotypes of the older adult and increase recognition of the value of working with older adults.

Furin cleavage of SARS-CoV-2 Spike promotes but is not essential for infection and cell-cell fusion

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects cells by binding to the host cell receptor Ace2 and undergoing virus-host membrane fusion. Fusion is triggered by the protease TMPRSS2, which processes the viral Spike (S) protein to reveal the fusion peptide. SARS-CoV-2 has evolved a multibasic site at the S1-S2 boundary, which is thought to be cleaved by furin in order to prime S protein for TMPRSS2 processing. Here we show that CRISPR-Cas9 knockout of furin reduces, but does not prevent, the production of infectious SARS-CoV-2 virus. Comparing S processing in furin knockout cells to multibasic site mutants reveals that while loss of furin substantially reduces S1-S2 cleavage it does not prevent it. SARS-CoV-2 S protein also mediates cell-cell fusion, potentially allowing virus to spread virion-independently. We show that loss of furin in either donor or acceptor cells reduces, but does not prevent, TMPRSS2-dependent cell-cell fusion, unlike mutation of the multibasic site that completely prevents syncytia formation. Our results show that while furin promotes both SARS-CoV-2 infectivity and cell-cell spread it is not essential, suggesting furin inhibitors will not prevent viral spread.

[Ten questions about bacterial vaginosis]. / La vaginose bactérienne en 10 questions.

The physiopathology of bacterial vaginosis (BV), the ultimate stage of vaginal dysbiosis, has benefited from recent advances in molecular biology, highlighting, among others, the important role of A. vaginae. Certain immunological specificities (variants of TLR4, elevation of IL-1ß, for example) explain the variations in the prevalence of this infection, the poor clinical and cellular inflammatory response and the promoting influence of BV on the acquisition and progression of some sexually transmitted infections. These advances do not fully elucidate the causes of the high rate of recurrences. Some risk factors for relapses of BV have been identified such as tobacco use, stress or hygienic errors have been associated to relapses of BV. However, other paths are beginning to be explored such as the role of sexual transmission, the resistance of certain bacteria associated to BV to nitroimidazoles or the lack of efficacy of conventional treatments on dysbiosis itself. Taking into acount this vaginal dysbiosis appears to be important or even essential to better control the natural history of HPV-hr infection or improve the success rate of IVF, for example. Despite heterogeneous results, the use of probiotics as a complement to conventional treatments (nitroimidazoles, dequalinium chloride) has demonstrated a preventive effect on BV recurrences. Further studies are needed to customize the contribution of probiotics (or synbiotics) according to the individual specificities of the vaginal microbiome.

GRAF2, WDR44, and MICAL1 mediate Rab8/10/11-dependent export of E-cadherin, MMP14, and CFTR ΔF508.

In addition to the classical pathway of secretion, some transmembrane proteins reach the plasma membrane through alternative routes. Several proteins transit through endosomes and are exported in a Rab8-, Rab10-, and/or Rab11-dependent manner. GRAFs are membrane-binding proteins associated with tubules and vesicles. We found extensive colocalization of GRAF1b/2 with Rab8a/b and partial with Rab10. We identified MICAL1 and WDR44 as direct GRAF-binding partners. MICAL1 links GRAF1b/2 to Rab8a/b and Rab10, and WDR44 binds Rab11. Endogenous WDR44 labels a subset of tubular endosomes, which are closely aligned with the ER via binding to VAPA/B. With its BAR domain, GRAF2 can tubulate membranes, and in its absence WDR44 tubules are not observed. We show that GRAF2 and WDR44 are essential for the export of neosynthesized E-cadherin, MMP14, and CFTR ΔF508, three proteins whose exocytosis is sensitive to ER stress. Overexpression of dominant negative mutants of GRAF1/2, WDR44, and MICAL1 also interferes with it, facilitating future studies of Rab8/10/11-dependent exocytic pathways of central importance in biology.

Nickel reduces calcium dependent dimerization in neural cadherin.

Cadherins are the transmembrane component in adherens junctions, structures that link the actin cytoskeletons in adjacent cells within solid tissues including neurological synapses, epithelium and endothelium. Cell-cell adhesion by cadherins requires the binding of calcium ions to specific sites in the extracellular region. Given the complexity of the cell adhesion microenvironment, we are investigating whether other divalent cations might affect calcium-dependent dimerization of neural (N) cadherin. The studies reported herein characterize the impact of binding physiological magnesium(ii) or neurotoxic nickel(ii) on calcium-dependent N-cadherin function. Physiological levels of magnesium have only a small effect on the calcium-binding affinity and calcium-induced dimerization of N-cadherin. However, a tenfold lower concentration of nickel decreases the apparent calcium-binding affinity and calcium-induced dimerization of N-cadherin. Competitive binding studies indicate that the apparent dissociation constants for nickel and magnesium are 0.2 mM and 2.5 mM, respectively. These Kd values are consistent with concentrations observed for a range of divalent cations in the extracellular space. Results from these studies indicate that calcium-induced dimerization by N-cadherin is attenuated by natural and non-physiological divalent cations in the extracellular microenvironment.

FBP17 and CIP4 recruit SHIP2 and lamellipodin to prime the plasma membrane for fast endophilin-mediated endocytosis.

Endocytosis mediates the cellular uptake of micronutrients and the turnover of plasma membrane proteins. Clathrin-mediated endocytosis is the major uptake pathway in resting cells1, but several clathrin-independent endocytic routes exist in parallel2,3. One such pathway, fast endophilin-mediated endocytosis (FEME), is not constitutive but triggered upon activation of certain receptors, including the ß1 adrenergic receptor4. FEME activates promptly following stimulation as endophilin is pre-enriched by the phosphatidylinositol-3,4-bisphosphate-binding protein lamellipodin4,5. However, in the absence of stimulation, endophilin foci abort and disassemble after a few seconds. Looking for additional proteins involved in FEME, we found that 20 out of 65 BAR domain-containing proteins tested colocalized with endophilin spots. Among them, FBP17 and CIP4 prime the membrane of resting cells for FEME by recruiting the 5'-lipid phosphatase SHIP2 and lamellipodin to mediate the local production of phosphatidylinositol-3,4-bisphosphate and endophilin pre-enrichment. Membrane-bound GTP-loaded Cdc42 recruits FBP17 and CIP4, before being locally deactivated by RICH1 and SH3BP1 GTPase-activating proteins. This generates the transient assembly and disassembly of endophilin spots, which lasts 5-10 seconds. This mechanism periodically primes patches of the membrane for prompt responses upon FEME activation.

Publisher Correction: FBP17 and CIP4 recruit SHIP2 and lamellipodin to prime the plasma membrane for fast endophilin-mediated endocytosis.

In the version of this Letter originally published, the name of co-author Safa Lucken-Ardjomande Häsler was coded wrongly, resulting in it being incorrect when exported to citation databases. This has been corrected, though no visible changes will be apparent.

High power generation of THz from 1550-nm photoconductive emitters.

Two photoconductive emitters - one with a self-complementary square spiral antenna, and the other with a resonant slot antenna - were fabricated on a GaAs epilayer embedded with ErAs quantum dots. Driven with 1550 nm mode-locked lasers, ~117 µW broadband THz power was generated from the device with the spiral antenna, and ~1.2 µW from the device with resonant slot antenna. The optical-to-THz conversion is through extrinsic photoconductivity.

A Flat BAR Protein Promotes Actin Polymerization at the Base of Clathrin-Coated Pits.

Multiple proteins act co-operatively in mammalian clathrin-mediated endocytosis (CME) to generate endocytic vesicles from the plasma membrane. The principles controlling the activation and organization of the actin cytoskeleton during mammalian CME are, however, not fully understood. Here, we show that the protein FCHSD2 is a major activator of actin polymerization during CME. FCHSD2 deletion leads to decreased ligand uptake caused by slowed pit maturation. FCHSD2 is recruited to endocytic pits by the scaffold protein intersectin via an unusual SH3-SH3 interaction. Here, its flat F-BAR domain binds to the planar region of the plasma membrane surrounding the developing pit forming an annulus. When bound to the membrane, FCHSD2 activates actin polymerization by a mechanism that combines oligomerization and recruitment of N-WASP to PI(4,5)P2, thus promoting pit maturation. Our data therefore describe a molecular mechanism for linking spatiotemporally the plasma membrane to a force-generating actin platform guiding endocytic vesicle maturation.

Sensory-Neuropathy-Causing Mutations in ATL3 Cause Aberrant ER Membrane Tethering.

The endoplasmic reticulum (ER) is a complex network of sheets and tubules that is continuously remodeled. The relevance of this membrane dynamics is underscored by the fact that mutations in atlastins (ATLs), the ER fusion proteins in mammals, cause neurodegeneration. How defects in this process disrupt neuronal homeostasis is unclear. Using electron microscopy (EM) volume reconstruction of transfected cells, neurons, and patient fibroblasts, we show that hereditary sensory and autonomic neuropathy (HSAN)-causing ATL3 mutants promote aberrant ER tethering hallmarked by bundles of laterally attached ER tubules. In vitro, these mutants cause excessive liposome tethering, recapitulating the results in cells. Moreover, ATL3 variants retain their dimerization-dependent GTPase activity but are unable to promote membrane fusion, suggesting a defect in an intermediate step of the ATL3 functional cycle. Our data show that the effects of ATL3 mutations on ER network organization go beyond a loss of fusion and shed light on neuropathies caused by atlastin defects.

Eps15R and clathrin regulate EphB2-mediated cell repulsion.

Expression of Eph receptors and their ligands, the ephrins, have important functions in boundary formation and morphogenesis in both adult and embryonic tissue. The EphB receptors and ephrinB ligands are transmembrane proteins that are expressed in different cells and their interaction drives cell repulsion. For cell repulsion to occur, trans-endocytosis of the inter-cellular receptor-ligand EphB-ephrinB complex is required. The molecular mechanism underlying trans-endocytosis is poorly defined. Here we show that the process is clathrin- and Eps15R-mediated using Co115 colorectal cell lines stably expressing EphB2 and ephrinB1. Cell repulsion in co-cultures of EphB2- and ephrinB1-expressing cells is significantly reduced by knockdown of Eps15R but not Eps15. A novel interaction motif in Eps15R, DPFxxLDPF, is shown to bind directly to the clathrin terminal domain in vitro. Moreover, the interaction between Eps15R and clathrin is required for EphB2-mediated cell repulsion as shown in a rescue experiment in the EphB2 co-culture assay where wild type Eps15R but not the clathrin-binding mutant rescues cell repulsion. These results provide the first evidence that Eps15R together with clathrin control EphB/ephrinB trans-endocytosis and thereby cell repulsion.

Friction Mediates Scission of Tubular Membranes Scaffolded by BAR Proteins.

Membrane scission is essential for intracellular trafficking. While BAR domain proteins such as endophilin have been reported in dynamin-independent scission of tubular membrane necks, the cutting mechanism has yet to be deciphered. Here, we combine a theoretical model, in vitro, and in vivo experiments revealing how protein scaffolds may cut tubular membranes. We demonstrate that the protein scaffold bound to the underlying tube creates a frictional barrier for lipid diffusion; tube elongation thus builds local membrane tension until the membrane undergoes scission through lysis. We call this mechanism friction-driven scission (FDS). In cells, motors pull tubes, particularly during endocytosis. Through reconstitution, we show that motors not only can pull out and extend protein-scaffolded tubes but also can cut them by FDS. FDS is generic, operating even in the absence of amphipathic helices in the BAR domain, and could in principle apply to any high-friction protein and membrane assembly.

Canine hepatozoonosis in southeastern Bahia, Brazil.

In Brazil, canine hepatozoonosis is a tick-borne subclinical hemoparasitosis caused by a protozoa Hepatozoon canis and is highly prevalent in dogs in rural areas. An epizootiological study was conducted to investigate the prevalence of H. canis in the canine population of Ituberá, Bahia, and to analyze any associated risk factors. Blood samples were collected from 380 dogs and determined the presence of the protozoan by performing capillary blood smear and polymerase chain reaction (PCR). Epizootiological data were collected by asking dog owners to answer a structured questionnaire. H. canis gamonts were not detected in the blood smears. However, PCR detected H. canis in 163/380 (42.9%) dogs examined. Physical examination and anamnesis indicated 105 (64.4%) positive asymptomatic dogs. Hematological alterations were observed in 115 (70.5%) infected dogs. No clinical, hematological, or epizootiological variable was found to be significantly associated to the infection. In conclusion, the high prevalence of H. canis infection in local dogs may be because of the peri-urban features of this municipality. Moreover, to the best of our knowledge, this study the first study to report H. canis infection in the State of Bahia.

How curvature-generating proteins build scaffolds on membrane nanotubes.

Bin/Amphiphysin/Rvs (BAR) domain proteins control the curvature of lipid membranes in endocytosis, trafficking, cell motility, the formation of complex subcellular structures, and many other cellular phenomena. They form 3D assemblies that act as molecular scaffolds to reshape the membrane and alter its mechanical properties. It is unknown, however, how a protein scaffold forms and how BAR domains interact in these assemblies at protein densities relevant for a cell. In this work, we use various experimental, theoretical, and simulation approaches to explore how BAR proteins organize to form a scaffold on a membrane nanotube. By combining quantitative microscopy with analytical modeling, we demonstrate that a highly curving BAR protein endophilin nucleates its scaffolds at the ends of a membrane tube, contrary to a weaker curving protein centaurin, which binds evenly along the tube's length. Our work implies that the nature of local protein-membrane interactions can affect the specific localization of proteins on membrane-remodeling sites. Furthermore, we show that amphipathic helices are dispensable in forming protein scaffolds. Finally, we explore a possible molecular structure of a BAR-domain scaffold using coarse-grained molecular dynamics simulations. Together with fluorescence microscopy, the simulations show that proteins need only to cover 30-40% of a tube's surface to form a rigid assembly. Our work provides mechanical and structural insights into the way BAR proteins may sculpt the membrane as a high-order cooperative assembly in important biological processes.

Electronic Enhancement of the Exciton Coherence Time in Charged Quantum Dots.

Minimizing decoherence due to coupling of a quantum system to its fluctuating environment is at the forefront of quantum information and photonics research. Nature sets the ultimate limit, however, given by the strength of the system's coupling to the electromagnetic field. Here, we establish the ability to electronically control this coupling and enhance the optical coherence time of the charged exciton transition in quantum dots embedded in a photonic waveguide. By manipulating the electronic wave functions through an applied lateral electric field, we increase the coherence time from ∼1.4 to ∼2.7 ns. Numerical calculations reveal that longer coherence arises from the separation of charge carriers by up to ∼6 nm, which leads to a 30% weaker transition dipole moment. The ability to electronically control the coherence time opens new avenues for quantum communication and novel coupling schemes between distant qubits.