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Abstract Adapting to different environments throughout daily activities requires flexibility in allocating attention. Compromised dual-tasking can hinder mobility, increase fall risk, and decrease functional independence in patients with essential tremor, who exhibit both mobility and cognitive impairments. We evaluated motor and cognitive dual-task effects and task prioritization in 15 people with Essential Tremor (ET) and 15 age-matched people without ET during a standard and more challenging water-carry TUG. Task-specific interference was evaluated by calculating motor and cognitive dual-task effects, whereas task prioritization was assessed by contrasting the cognitive dual-task effect with the motor dual-task effect. The simultaneous performance of two tasks did not differentially impact motor or cognitive performance in either group, and both groups prioritized cognitive task performance in standard and water-carry TUG assessments. This study enhances our understanding of motor-cognitive interactions in individuals with essential tremor. These insights could lead to patient-centered approaches to therapy to improve functional performance in dynamic daily environments.

Background: Assessing for significant proteinuria in pregnancy (SPIP) stands as a key indicator for diagnosing preeclampsia. However, the initial method typically employed for this assessment, the urine dipstick test, often yields inaccurate results. While a 24-h urine collection is considered the most reliable test, its implementation can lead to delays in diagnosis, potentially affecting both maternal and fetal well-being. The urine protein–creatinine (P/Cr) ratio can be used as an alternative to 24-h urine protein analysis, but its diagnostic accuracy has remained uncertain. There is a need to compare the diagnostic accuracy of urine P/Cr ratio and dipstick urinalysis for SPIP, especially in resource-poor settings. Objectives: To determine and compare the diagnostic accuracy of urine P/Cr ratio and dipstick urinalysis in a spot urine specimen for the diagnosis of SPIP among women evaluated for preeclampsia using 24-h urine protein excretions as a gold standard. Design: This is a comparative cross-sectional study. Methods: The study involved 82 singleton pregnant women evaluated for preeclampsia from 20 weeks of gestation who underwent dipstick and P/Cr ratio tests in the same urine sample. Women at risk of preeclampsia were given a specimen container for the collection of urine samples on an outpatient basis. Participants were trained and told to collect the urine sample 24 h prior to their next antenatal appointment. However, those on admission and evaluated for preeclampsia had their 24-h urine collected in the hospital. The outcome measures included sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio and accuracy for the two tests. Significant proteinuria was defined as a P/Cr ratio >0.27 or ⩾2+ of proteinuria on the dipstick test. Preeclampsia was confirmed in women with both high blood pressure and SPIP. Results: The mean age of participants was 28.65 ± 5.76 years. Comparatively, the diagnostic accuracy (91.46% (95% CI = 83.29–96.59) vs 59.76% (95% CI = 48.34–70.44), p = 0.001), sensitivity (94.74% vs 70.00%, p = 0.021), specificity (84.00% vs 43.75%, p = 0.001), negative predictive value (87.50% vs 48.28%, p = 0.003) and positive predictive value (93.10% vs 66.04%, p = 0.001), respectively, were higher for the spot urine P/Cr ratio than dipstick test. In addition, the positive likelihood ratio and the negative likelihood ratio for spot urine P/Cr ratio versus dipstick test were (1.93 vs 1.24) and (0.07 vs 0.69), respectively. Conclusion: The spot urine P/Cr has superior diagnostic accuracy in the determination of significant proteinuria in pregnant women being evaluated for preeclampsia than the widely used dipstick test. A more robust multicenter study is needed to compare the diagnostic accuracy of spot urine PCR with the standard 24-h urine protein in low-income settings.

Summary:. Autologous fat transfer is fast becoming a common adjunct procedure in plastic surgical operations, especially in breast reconstruction. Postharvest fat processing can be performed actively or passively with various techniques. All techniques require the final step of loading the harvested fat into a syringe for injection. We describe here an innovative and elegant technique for safer and more efficient loading of the plunger back into the barrel of a fat-filled syringe before injection. This technique improves ease of loading, reduces loss of harvested fat, and eliminates the risk of bodily fluid splash.

Human metapneumovirus (HMPV) is an important cause of acute respiratory tract infection and causes significant morbidity and mortality. There is no specific antiviral drug to treat HMPV or vaccine to prevent HMPV. This study determined if probenecid, a host-targeting antiviral drug, had prophylactic (pre-virus) or therapeutic (post-virus) efficacy to inhibit HMPV replication in LLC-MK2 cells in vitro and in the lungs of BALB/c mice. This study showed that ≥0.5 μM probenecid significantly inhibited HMPV replication in vitro, and 2–200 mg/kg probenecid prophylaxis or treatment reduced HMPV replication in BALB/c mice.

Influenza viruses cause epidemics and can cause pandemics with substantial morbidity with some mortality every year. Seasonal influenza vaccines have incomplete effectiveness and elicit a narrow antibody response that often does not protect against mutations occurring in influenza viruses. Thus, various vaccine approaches have been investigated to improve safety and efficacy. Here, we evaluate an mRNA influenza vaccine encoding hemagglutinin (HA) proteins in a BALB/c mouse model. The results show that mRNA vaccination elicits neutralizing and serum antibodies to each influenza virus strain contained in the current quadrivalent vaccine that is designed to protect against four different influenza viruses including two influenza A viruses (IAV) and two influenza B (IBV), as well as several antigenically distinct influenza virus strains in both hemagglutination inhibition assay (HAI) and virus neutralization assays. The quadrivalent mRNA vaccines had antibody titers comparable to the antibodies elicited by the monovalent vaccines to each tested virus regardless of dosage following an mRNA booster vaccine. Mice vaccinated with mRNA encoding an H1 HA had decreased weight loss and decreased lung viral titers compared to mice not vaccinated with an mRNA encoding an H1 HA. Overall, this study demonstrates the efficacy of mRNA-based seasonal influenza vaccines are their potential to replace both the currently available split-inactivated, and live-attenuated seasonal influenza vaccines.

Molecular probes with the ability to differentiate between subcellular variations in acidity levels remain important for the investigation of dynamic cellular processes and functions. In this context, a series of cyclic peptide and PEG bio-conjugated dual near-infrared emissive BF2-azadipyrromethene fluorophores with maxima emissions at 720 nm (at pH > 6) and 790 nm (at pH < 5) have been developed and their aqueous solution photophysical properties determined. Their inter-converting emissions and fluorescence lifetime characteristics were exploited to track their spatial and temporal progression from first contact with the plasma membrane to subcellular locales to their release within extracellular vesicles. A pH-dependent reversible phenolate/phenol interconversion on the fluorophore controlled the dynamic changes in dual emission responses and corresponding lifetime changes. Live-cell confocal microscopy experiments in the metastatic breast cancer cell line MDA-MB-231 confirmed the usability of the dual emissive properties for imaging over prolonged periods. All three derivatives performed as probes capable of real-time continuous imaging of fundamental cellular processes such as plasma membrane interaction, tracking endocytosis, lysosomal/large acidic vesicle accumulation, and efflux within extracellular vesicles without perturbing cellular function. Furthermore, fluorescence lifetime imaging microscopy provided valuable insights regarding fluorophore progression through intracellular microenvironments over time. Overall, the unique photophysical properties of these fluorophores show excellent potential for their use as information-rich probes.

Flexibility in performing various movements like standing, walking, and turning is crucial for navigating dynamic environments in daily life. Individuals with essential tremor often experience movement difficulties that can affect these postural transitions, limiting mobility and independence. Yet, little research has examined the performance of postural transitions in people with essential tremor. Therefore, we assessed postural transition performance using two versions of the timed up and go test: the standard version and a more complex water-carry version. We examined the total duration of the standard and water-carry timed up and go in 15 people with and 15 people without essential tremor. We also compared the time taken for each phase (sit-to-stand phase, straight-line walk phase, stand-to-sit phase) and the turning velocity between groups. Our findings revealed decreased performance across all phases of standard and water-carry timed up and go assessments. Further, both ET and non-ET groups exhibited reduced performance during the water-carry timed up and go compared to the standard timed up and go. Evaluating specific phases of the timed up and go offers valuable insights into functional movement performance in essential tremor, permitting more tailored therapeutic interventions to improve functional performance during activities of daily living.

We examined the effect of probenecid in regulating the ERK and JNK downstream MAPK pathways affecting respiratory syncytial virus replication. Background: We have previously shown that probenecid inhibits RSV, influenza virus, and SARS-CoV-2 replication in vitro in preclinical animal models and in humans. In a Phase two randomized, placebo-controlled, single-blind, dose range-finding study using probenecid to treat non-hospitalized patients with symptomatic, mild-to-moderate COVID-19, we previously showed that a 1000 mg twice daily treatment for 5 days reduced the median time to viral clearance from 11 to 7 days, and a 500 mg twice daily treatment for 5 days reduced the time to viral clearance from 11 to 9 days more than the placebo. Methods: In this study, we sought to determine the mechanism of action of the probenecid inhibition of RSV replication in human respiratory epithelial (A549) cells. Results: We show that probenecid inhibits the RSV-induced phosphorylation of JNKs and ERKs and the downstream phosphorylation of c-jun, a component of the AP-1 transcription complex needed for virus replication. The inhibition of JNKs by probenecid reversed the repression of transcription factor HNF-4. Conclusion: The probenecid inhibition of JNK and ERK phosphorylation involves the MAPK pathway that precludes virus replication. [ABSTRACT FROM AUTHOR]

Introduction: In the past year, the use of large language models (LLMs) has generated significant interest and excitement because of their potential to revolutionise various fields, including medical education for aspiring physicians. Although medical students undergo a demanding educational process to become competent health care professionals, the emergence of LLMs presents a promising solution to challenges like information overload, time constraints and pressure on clinical educators. However, integrating LLMs into medical education raises critical concerns and challenges for educators, professionals and students. This systematic review aims to explore LLM applications in medical education, specifically their impact on medical students' learning experiences. Methods: A systematic search was performed in PubMed, Web of Science and Embase for articles discussing the applications of LLMs in medical education using selected keywords related to LLMs and medical education, from the time of ChatGPT's debut until February 2024. Only articles available in full text or English were reviewed. The credibility of each study was critically appraised by two independent reviewers. Results: The systematic review identified 166 studies, of which 40 were found by review to be relevant to the study. Among the 40 relevant studies, key themes included LLM capabilities, benefits such as personalised learning and challenges regarding content accuracy. Importantly, 42.5% of these studies specifically evaluated LLMs in a novel way, including ChatGPT, in contexts such as medical exams and clinical/biomedical information, highlighting their potential in replicating human‐level performance in medical knowledge. The remaining studies broadly discussed the prospective role of LLMs in medical education, reflecting a keen interest in their future potential despite current constraints. Conclusions: The responsible implementation of LLMs in medical education offers a promising opportunity to enhance learning experiences. However, ensuring information accuracy, emphasising skill‐building and maintaining ethical safeguards are crucial. Continuous critical evaluation and interdisciplinary collaboration are essential for the appropriate integration of LLMs in medical education. Addressing the hype around incorporating large language models and ChatGPT into medical education, Robinson et al. outline how to do it right and wrong. [ABSTRACT FROM AUTHOR]

We present a comprehensive study of the physical origin of radio emission in optical quasars at redshifts z < 2.5. We focus particularly on the associations between compact radio emission, dust reddening, and outflows identified in our earlier work. Leveraging the deepest low-frequency radio data available to date (LoTSS Deep DR1), we achieve radio detection fractions of up to 94%, demonstrating the virtual ubiquity of radio emission in quasars, and a continuous distribution in radio loudness. Through our analysis of radio properties, combined with spectral energy distribution modelling of deep multiwavelength photometry, we establish that the primary source of radio emission in quasars is the active galactic nucleus (AGN), rather than star formation. Modelling the dust reddening of the accretion disc emission shows a continuous increase in radio detection in quasars as a function of the reddening parameter E(B − V), suggesting a causal link between radio emission and dust reddening. Confirming previous findings, we observe that the radio excess in red quasars is most pronounced for sources with compact radio morphologies and intermediate radio loudness. We find a significant increase in [O III] and C IV outflow velocities for red quasars not seen in our control sample, with particularly powerful [O III] winds in those around the threshold from radio-quiet to radio-loud. Based on the combined characterisation of radio, reddening, and outflow properties in our sample, we favour a model in which the compact radio emission observed in quasars originates in compact radio jets and their interaction with a dusty, circumnuclear environment. In particular, our results align with the theory that jet-induced winds and shocks resulting from this interaction are the origin of the enhanced radio emission in red quasars. Further investigation of this model is crucial for advancing our understanding of quasar feedback mechanisms and their role in galaxy evolution. [ABSTRACT FROM AUTHOR]

Structures at serine‐proline sites in proteins were analyzed using a combination of peptide synthesis with structural methods and bioinformatics analysis of the PDB. Dipeptides were synthesized with the proline derivative (2S,4S)‐(4‐iodophenyl)hydroxyproline [hyp(4‐I‐Ph)]. The crystal structure of Boc‐Ser‐hyp(4‐I‐Ph)‐OMe had two molecules in the unit cell. One molecule exhibited cis‐proline and a type VIa2 β‐turn (BcisD). The cis‐proline conformation was stabilized by a C–H/O interaction between Pro C–Hα and the Ser side‐chain oxygen. NMR data were consistent with stabilization of cis‐proline by a C–H/O interaction in solution. The other crystallographically observed molecule had trans‐Pro and both residues in the PPII conformation. Two conformations were observed in the crystal structure of Ac‐Ser‐hyp(4‐I‐Ph)‐OMe, with Ser adopting PPII in one and the β conformation in the other, each with Pro in the δ conformation and trans‐Pro. Structures at Ser‐Pro sequences were further examined via bioinformatics analysis of the PDB and via DFT calculations. Ser‐Pro versus Ala–Pro sequences were compared to identify bases for Ser stabilization of local structures. C–H/O interactions between the Ser side‐chain Oγ and Pro C–Hα were observed in 45% of structures with Ser‐cis‐Pro in the PDB, with nearly all Ser‐cis‐Pro structures adopting a type VI β‐turn. 53% of Ser‐trans‐Pro sequences exhibited main‐chain COi•••HNi+3 or COi•••HNi+4 hydrogen bonds, with Ser as the i residue and Pro as the i + 1 residue. These structures were overwhelmingly either type I β‐turns or N‐terminal capping motifs on α‐helices or 310‐helices. These results indicate that Ser‐Pro sequences are particularly potent in favoring these structures. In each, Ser is in either the PPII or β conformation, with the Ser Oγ capable of engaging in a hydrogen bond with the amide N–H of the i + 2 (type I β‐turn or 310‐helix; Ser χ1t) or i + 3 (α‐helix; Ser χ1g+) residue. Non‐proline cis amide bonds can also be stabilized by C–H/O interactions. [ABSTRACT FROM AUTHOR]

Executive control of movement enables inhibiting impulsive responses critical for successful navigation of the environment. Circuits mediating stop commands involve prefrontal and basal ganglia structures with fMRI evidence demonstrating increased activity during response inhibition in the dorsolateral prefrontal cortex (dlPFC)—often ascribed to maintaining task attentional demands. Using direct intraoperative cortical recordings in male and female human subjects, we investigated oscillatory dynamics along the rostral-caudal axis of dlPFC during a modified Go/No-go task, probing components of both proactive and reactive motor control. We assessed whether cognitive control is topographically organized along this axis and observed that low-frequency power increased prominently in mid-rostral dlPFC when inhibiting and delaying responses. These findings provide evidence for a key role for mid-rostral dlPFC low-frequency oscillations in sculpting motor control. [ABSTRACT FROM AUTHOR]

We present spatially resolved VLT/SINFONI spectroscopy with adaptive optics of type-2 active galactic nuclei (AGN) from the SINFONI Survey for Unveiling the Physics and Effect of Radiative feedback (SUPER), which targeted X-ray bright (L2 − 10 keV ≳ 1042 erg s−1) AGN at cosmic noon (z ∼ 2). Our analysis of the rest-frame optical spectra unveils ionised outflows in all seven examined targets, as traced via [O III]λ5007 line emission, moving at v ≳ 600 km s−1. These outflows are clearly spatially resolved in six objects and extend on 2–4 kpc scales, but they are marginally resolved in the remaining one object. Interestingly, these SUPER type-2 AGN are all heavily obscured sources (NH ≳ 1023 cm−2) and host faster ionised outflows than their type-1 counterparts within the same range of bolometric luminosity (Lbol ∼ 1044.8 − 46.5 erg s−1). SUPER has hence provided observational evidence that the dichotomy of type-1 to type-2 at z ∼ 2 might not be driven simply by projection effects, but might reflect two distinct obscuring life stages of active galaxies, as predicted by evolutionary models. Within this picture, SUPER type-2 AGN might be undergoing the blow-out phase, where the large amount of obscuring material efficiently accelerates large-scale outflows via radiation pressure on dust, eventually unveiling the central active nucleus and signaling the start of the bright, unobscured type-1 AGN phase. Moreover, the velocities of the overall population of ionised outflows detected in SUPER are comparable with the escape speed of their dark matter haloes, and they are in general high enough to reach distances of 30–50 kpc from the centre. These outflows are hence likely to sweep away the gas (at least) out of the baryonic disk and/or to heat the host gas reservoir, thus reducing and possibly quenching star formation. [ABSTRACT FROM AUTHOR]

Small-scale winds driven from accretion discs surrounding active galactic nuclei (AGN) are expected to launch kpc-scale outflows into their host galaxies. However, the ways in which the structure of the interstellar medium (ISM) affects the multiphase content and impact of the outflow remain uncertain. We present a series of numerical experiments featuring a realistic small-scale AGN wind with velocity |$5\times 10^3 \!-\! 10^4\rm {\ km\ s^{-1}}$| interacting with an isolated galaxy disc with a manually controlled clumpy ISM, followed at sub-pc resolution. Our simulations are performed with arepo and probe a wide range of AGN luminosities (⁠|$L_{\rm {AGN}}{=} 10^{43-47}\rm {\ erg\ s^{-1}}$|⁠) and ISM substructures. In homogeneous discs, the AGN wind sweeps up an outflowing, cooling shell, where the emerging cold phase dominates the mass and kinetic energy budgets, reaching a momentum flux |$\dot{p} \approx 7\ L/c$|⁠. However, when the ISM is clumpy, outflow properties are profoundly different. They contain small, long-lived (⁠|$\gtrsim 5\ \rm {Myr}$|⁠), cold (⁠|$T{\lesssim }10^{4.5}{\rm {\ K}}$|⁠) cloudlets entrained in the faster, hot outflow phase, which are only present in the outflow if radiative cooling is included in the simulation. While the cold phase dominates the mass of the outflow, most of the kinetic luminosity is now carried by a tenuous, hot phase with |$T \gtrsim 10^7 \, \rm K$|⁠. While the hot phases reach momentum fluxes |$\dot{p} \approx (1 - 5)\ L/c$|⁠ , energy-driven bubbles couple to the cold phase inefficiently, producing modest momentum fluxes |$\dot{p} \lesssim L/c$| in the fast-outflowing cold gas. These low momentum fluxes could lead to the outflows being misclassified as momentum-driven using common observational diagnostics. We also show predictions for scaling relations between outflow properties and AGN luminosity and discuss the challenges in constraining outflow driving mechanisms and kinetic coupling efficiencies using observed quantities. [ABSTRACT FROM AUTHOR]

Scholars of entrepreneurship, business, and economics have been reluctant to consider Hip Hop as a viable means for research and theory-building. Oddly enough, through the 1970s – a period that was generally characterized by stagnation and high unemployment – Hip Hop captivated audiences around the globe, creating innovative and diverse market opportunities for a host of different communities. The term 'Hip Hop Mogul' emerged to describe artists whose commercial viability appealed to varied sensibilities and disparate public spheres. Who are these Hip Hop Moguls? What are the interests of these Hip Hop Moguls? Drawing on lyrical content from a sample of Hip Hop Moguls (n = 15), we examine the discursive frameworks that make-up Moguldom, its politics, and its ways of being. Ultimately, our findings shed light on the different ways that marginalized communities negotiate antagonistic economic relations and disrupt traditional business paradigms. [ABSTRACT FROM AUTHOR]

Tarda is an ungrouped, hydrated carbonaceous chondrite (C2‐ung) that was seen to fall in Morocco in 2020. Early studies showed that Tarda chemically resembles another ungrouped chondrite, Tagish Lake (C2‐ung), which has previously been linked to the dark D‐type asteroids. Samples of D‐type asteroids provide an important opportunity to investigate primitive conditions in the outer solar system. We show that Tarda contains few intact chondrules and refractory inclusions and that its composition is dominated by secondary Mg‐rich phyllosilicates (>70 vol%), carbonates, oxides, and Fe‐sulfides that formed during extensive water–rock reactions. Quantitative assessment of first‐order reversal curve (FORC) diagrams shows that Tarda's magnetic mineralogy (i.e., framboidal magnetite) is comparable to that of the CI chondrites and differs notably from that of most CM chondrites. These traits support a common formation process for magnetite in Tarda and the CI chondrites. Furthermore, Tarda's pre‐terrestrial paleomagnetic remanence is similar to that of Tagish Lake and samples returned from asteroid Ryugu, with a very weak paleointensity (<0.6 μT) suggesting that Tarda's parent body accreted more distally than that of the CM chondrites, possibly at a distance of >5.4–8.3 AU. An origin in the cold, outer regions of the solar system is further supported by the presence of distinct, porous clasts enriched in aliphatic‐rich organics that potentially retain a pristine interstellar composition. Together, our observations support a genetic relationship between Tarda and Tagish Lake. [ABSTRACT FROM AUTHOR]

Dating back to when the inventor of the game, James Naismith, developed a mentoring relationship with John McClendon one of the African American pioneers in basketball (founder of the "fast-break"), there are countless examples of these intersections. Entering the college basketball culture as the most decorated recruiting class in National Collegiate Athletic Association basketball history, the University of Michigan Fab Five's legacy catalyzes a new era of American basketball culture. Gracefully talented, the Fab Five abruptly disrupted the institution of basketball, the National Collegiate Athletic Association, and the identity of basketball athletes globally. This paper presents a sociocultural exploration of the residual impact of the Fab Five's legacy. As authentic, confident, and culturally competent, the five young men intentionally resisted and acknowledged the intersections of race, culture, and class within the college basketball culture. We critically assess the evolution of basketball culture, grounded by the sociocultural experiences of the Fab Five, imprinting upon contemporary generations of college basketball programs and their player. Through these experiences, the Fab Five's success through conflict, during their short stint in college basketball and beyond their professional careers trailblazed a path for the modern-day basketball athlete. Known for their style of play, their expression of fashion on and off the court, and eagerness to talk smack, the Fab Five backed up their talk with performance. Their performance on and off the court, revolutionized the culture of basketball; Even more, American society. The Fab Five's legacy is the cultural catalyst for basketball culture on all levels. [ABSTRACT FROM AUTHOR]

Human metapneumovirus (HMPV) is an important cause of acute respiratory tract infection and causes significant morbidity and mortality. There is no specific antiviral drug to treat HMPV or vaccine to prevent HMPV. This study determined if probenecid, a host-targeting antiviral drug, had prophylactic (pre-virus) or therapeutic (post-virus) efficacy to inhibit HMPV replication in LLC-MK2 cells in vitro and in the lungs of BALB/c mice. This study showed that ≥0.5 μM probenecid significantly inhibited HMPV replication in vitro, and 2–200 mg/kg probenecid prophylaxis or treatment reduced HMPV replication in BALB/c mice. [ABSTRACT FROM AUTHOR]