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1.
Oncol Ther ; 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39298037

RESUMEN

INTRODUCTION: Myelodysplastic syndromes (MDS) are characterized by bone marrow failure, peripheral blood cytopenias and a high risk of progression to acute myeloid leukemia (AML), which is associated with a poor prognosis and low survival rates. This study combined surveys with patient chart reviews to document real-world clinical practice and burden of MDS, including perspectives of physicians, patients and caregivers and underlying discrepancies. METHODS: Physicians in major European countries and the US provided information on 1445 patients, stratified into lower- (LR) and higher-risk (HR) MDS. Patients had the opportunity to complete questionnaires describing the impact of MDS. Caregivers had the option to report on the burden of caring for a patient with MDS. RESULTS: While supportive treatment was common, mainly with erythropoietins (52%), anti-AML agents were more frequently used in HR than in LR patients (70% vs 20%), while HR patients generally received more transfusions (48% vs 36%). Symptoms with the largest discordance between patient vs physician reporting were excessive bruising (30% vs 14%), GI side effects (19% vs 6%) and feeling tired or fatigued (68% vs 56%). A bigger impact of fatigue was reported on the European Organization for the Research and Treatment of Cancer Quality of Life questionnaire (EORTC QLQ-C30) for HR vs LR patients (43.2 vs 36.5 on a scale from 0 to 100). There was discordance between caregivers vs physicians on reporting of weekly caregiver hours (45.4 vs 29.2) with a Zarit Burden Interview score (ZBI, score 0-88) of 25.4. CONCLUSIONS: Patients reported a higher frequency than their physicians of top symptoms, with MDS-related disruptions in daily life for both patients and caregivers. There is a need for new therapeutic strategies, along with shared understanding and decision making among patients, caregivers and physicians, to optimize disease management and improve quality of life in people living with MDS.

3.
ACS Nano ; 18(37): 25478-25488, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39236319

RESUMEN

SnSe, an environmental-friendly group-IV monochalcogenide semiconductor, demonstrates outstanding performance in various applications ranging from thermoelectric devices to solar energy harvesting. Its ultrathin films show promise in the fabrication of ferroelectric nonvolatile devices. However, the microscopic identification and manipulation of point defects in ultrathin SnSe single crystalline films, which significantly impact their electronic structure, have been inadequately studied. This study presents a comprehensive investigation of point defects in monolayer SnSe films grown via molecular beam epitaxy. By combining scanning tunneling microscopy (STM) characterization with first-principles calculations, we identified four types of atomic/molecular vacancies, four types of atomic substitutions, and three types of extrinsic defects. Notably, we have demonstrated the ability to convert a substitutional defect into a vacancy and to reposition an adsorbate by manipulating a single atom or molecule using an STM tip. We have also analyzed the local atomic displacement induced by the vacancies. This work provides a solid foundation for engineering the electronic structure of future SnSe-based nanodevices.

4.
JMIR Public Health Surveill ; 10: e54215, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39259172

RESUMEN

Background: Young men who have sex with men and young transgender women (YMSM-YTW) use online spaces to meet sexual partners with increasing regularity, and research shows that experiences of racism online mimics the real world. Objective: We analyzed differences by race and ethnicity in web-based and mobile apps used to meet sexual partners as reported by Chicago-based YMSM-YTW in 2016-2017. Methods: A racially and ethnically diverse sample of 643 YMSM-YTW aged 16-29 years were asked to name websites or mobile apps used to seek a sexual partner in the prior 6 months, as well as provide information about sexual partnerships from the same period. We used logistic regression to assess the adjusted association of race and ethnicity with (1) use of any website or mobile apps to find a sexual partner, (2) use of a "social network" to find a sexual partner compared to websites or mobile apps predominantly used for dating or hookups, (3) use of specific websites or mobile apps, and (4) reporting successfully meeting a sexual partner online among website or mobile app users. Results: While most YMSM-YTW (454/643, 70.6%) used websites or mobile apps to find sexual partners, we found that Black non-Hispanic YMSM-YTW were significantly less likely to report doing so (comparing White non-Hispanic to Black non-Hispanic: adjusted odds ratio [aOR] 1.74, 95% CI 1.10-2.76). Black non-Hispanic YMSM-YTW were more likely to have used a social network site to find a sexual partner (comparing White non-Hispanic to Black non-Hispanic: aOR 0.20, 95% CI 0.11-0.37), though this was only reported by one-third (149/454, 32.8%) of all app-using participants. Individual apps used varied by race and ethnicity, with Grindr, Tinder, and Scruff being more common among White non-Hispanic YMSM-YTW (93/123, 75.6%; 72/123, 58.5%; and 30/123, 24.4%, respectively) than among Black non-Hispanic YMSM-YTW (65/178, 36.5%; 25/178, 14%; and 4/178, 2.2%, respectively) and Jack'd and Facebook being more common among Black non-Hispanic YMSM-YTW (105/178, 59% and 64/178, 36%, respectively) than among White non-Hispanic YMSM-YTW (6/123, 4.9% and 8/123, 6.5%, respectively). Finally, we found that while half (230/454, 50.7%) of YMSM-YTW app users reported successfully meeting a new sexual partner on an app, Black non-Hispanic YMSM-YTW app users were less likely to have done so than White non-Hispanic app users (comparing White non-Hispanic to Black non-Hispanic: aOR 2.46, 95% CI 1.50-4.05). Conclusions: We found that Black non-Hispanic YMSM-YTW engaged with websites or mobile apps and found sexual partners systematically differently than White non-Hispanic YMSM-YTW. Our findings give a deeper understanding of how racial and ethnic sexual mixing patterns arise and have implications for the spread of sexually transmitted infections among Chicago's YMSM-YTW.


Asunto(s)
Homosexualidad Masculina , Aplicaciones Móviles , Parejas Sexuales , Personas Transgénero , Humanos , Aplicaciones Móviles/estadística & datos numéricos , Masculino , Adolescente , Estudios Transversales , Adulto Joven , Adulto , Femenino , Parejas Sexuales/psicología , Homosexualidad Masculina/estadística & datos numéricos , Homosexualidad Masculina/psicología , Personas Transgénero/estadística & datos numéricos , Personas Transgénero/psicología , Chicago , Etnicidad/estadística & datos numéricos , Etnicidad/psicología
5.
JMIR Public Health Surveill ; 10: e56571, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39264291

RESUMEN

Background: The COVID-19 pandemic resulted in a massive disruption in access to care and thus passive, hospital- and clinic-based surveillance programs. In 2020, the reported cases of Lyme disease were the lowest both across the United States and North Carolina in recent years. During this period, human contact patterns began to shift with higher rates of greenspace utilization and outdoor activities, putting more people into contact with potential vectors and associated vector-borne diseases. Lyme disease reporting relies on passive surveillance systems, which were likely disrupted by changes in health care-seeking behavior during the pandemic. Objective: This study aimed to quantify the likely under-ascertainment of cases of Lyme disease during the COVID-19 pandemic in the United States and North Carolina. Methods: We fitted publicly available, reported Lyme disease cases for both the United States and North Carolina prior to the year 2020 to predict the number of anticipated Lyme disease cases in the absence of the pandemic using a Bayesian modeling approach. We then compared the ratio of reported cases divided by the predicted cases to quantify the number of likely under-ascertained cases. We then fitted geospatial models to further quantify the spatial distribution of the likely under-ascertained cases and characterize spatial dynamics at local scales. Results: Reported cases of Lyme Disease were lower in 2020 in both the United States and North Carolina than prior years. Our findings suggest that roughly 14,200 cases may have gone undetected given historical trends prior to the pandemic. Furthermore, we estimate that only 40% to 80% of Lyme diseases cases were detected in North Carolina between August 2020 and February 2021, the peak months of the COVID-19 pandemic in both the United States and North Carolina, with prior ascertainment rates returning to normal levels after this period. Our models suggest both strong temporal effects with higher numbers of cases reported in the summer months as well as strong geographic effects. Conclusions: Ascertainment rates of Lyme disease were highly variable during the pandemic period both at national and subnational scales. Our findings suggest that there may have been a substantial number of unreported Lyme disease cases despite an apparent increase in greenspace utilization. The use of counterfactual modeling using spatial and historical trends can provide insight into the likely numbers of missed cases. Variable ascertainment of cases has implications for passive surveillance programs, especially in the trending of disease morbidity and outbreak detection, suggesting that other methods may be appropriate for outbreak detection during disturbances to these passive surveillance systems.


Asunto(s)
COVID-19 , Enfermedad de Lyme , Humanos , Enfermedad de Lyme/epidemiología , COVID-19/epidemiología , Estados Unidos/epidemiología , North Carolina/epidemiología , Estudios Retrospectivos , Pandemias , Teorema de Bayes
6.
Nano Lett ; 24(37): 11544-11550, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39254085

RESUMEN

We investigate the effect of Coulomb interactions on the electronic states of a single perovskite quantum dot (PQD), CsPbBr3, through scanning tunneling microscopy/spectroscopy (STM/S). Under a weak interaction regime, where the time-averaged occupation of electrons in a PQD remains zero, the peaks observed in the differential tunneling conductance (dI/dV) spectrum correspond to the single-particle density of states (DOS) without any electron-electron correlation. However, with a shorter tunnel distance between the STM tip and PQD, additional electrons are trapped in the QD, leading to a strong interaction regime with well-defined electronic fine structures due to the lifting of spin degeneracy in the conduction bands. Interestingly, we observe that the strong Coulomb interaction can modify the spin-orbit coupling (SOC) strength in the PQDs. We have concluded that the energy levels under a strong electron-electron interaction regime are of utmost importance since they will be applicable to electrically pumped PQD-based single photon quantum emitters.

7.
Neural Netw ; 180: 106694, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39293176

RESUMEN

We show that for stabilization of Boolean control networks (BCNs) with unobservable initial states, open-loop control and close-loop control are not equivalent. An example is given to illustrate the nonequivalence. Enlightened by the nonequivalence, we explore open-loop set stabilization of BCNs with unobservable initial states. More specifically, this issue is to investigate that for a given BCN, whether there exists a unified free control sequence that is effective for all initial states of the system to stabilize the system states to a given set. The criteria for open-loop set stabilization is derived and for any open-loop set stabilizable BCN, every time-optimal open-loop set stabilizer is proposed. Besides, we obtain the least upper bounds of two integers, which are respectively related to the global stabilization and partial stabilization of BCNs in the results of two literature articles. Using the methods in the two literature articles, the least upper bounds of the two integers cannot be obtained.

8.
Int J Drug Policy ; 132: 104558, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39226770

RESUMEN

BACKGROUND: Our goal in this report was to quantify the degree to which opioid prescription rates and socioeconomic correlates of income inequality predicted overdose deaths in the 1055 U.S. Midwest counties. The study follows up a state-level analysis which reported that opioid prescription rates, social capital and unemployment explained much of the variance in opioid overdose death rates (Heyman, McVicar, & Brownell, 2019). METHODS: We created a data set that included drug overdose death rates, opioid prescription rates, and correlates of income inequality. Given that the variables of interest varied at the state and county level, multilevel regression was our statistical approach. RESULTS: From 2006 to 2021, Midwest overdose drug deaths increased according to an exponential equation that closely approximated the equation that describes the increases in overdose deaths for the entire U.S. from 1978 to 2016 (e.g., Jalal et al., 2018). Retail opioid prescription sales increased from 2006 to 2012, but then declined so that by 2017 they were lower than in 2006. The regression analyses revealed that intergenerational income mobility was the strongest predictor of overdose deaths. The other consistently statistically significant predictors were opioid prescription rates, social capital, and unemployment rates. Together these predictors, plus pupil teacher ratios, single parent families, and attending college accounted for approximately 47 % of the variance in overdose death rates each year. In keeping with the decline in opioid prescription rates, the explanatory power of opioid prescription rates weakened over the course of the study. CONCLUSIONS: Overdose deaths increased at a constant exponential rate for the years that it was possible to apply our regression model. This occurred even though access to legal opioids decreased. What remained invariant was the predictive strength of intergenerational income mobility; each year it was the predictor that explained the most variance in overdose deaths.


Asunto(s)
Analgésicos Opioides , Sobredosis de Droga , Renta , Factores Socioeconómicos , Humanos , Sobredosis de Droga/mortalidad , Sobredosis de Droga/epidemiología , Analgésicos Opioides/envenenamiento , Renta/estadística & datos numéricos , Medio Oeste de Estados Unidos/epidemiología , Masculino , Femenino , Adulto , Desempleo/estadística & datos numéricos , Prescripciones de Medicamentos/estadística & datos numéricos
9.
Milbank Q ; 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39289915

RESUMEN

Policy Points Health care systems around the world rely on a range of methods to ensure the affordability of prescription drugs, including negotiating prices soon after drug approval and relying on formal clinical assessments that compare newly approved therapies with existing alternatives. The negotiation framework established under the Inflation Reduction Act is far more limited than other frameworks explored in this study. Adding elements from these frameworks could lead to more effective price negotiation in the United States. CONTEXT: In 2022, Congress passed the Inflation Reduction Act, which allowed Medicare, for the first time, to begin negotiating the prices for certain high-cost brand-name prescription drugs. Many other industrialized countries negotiate drug prices, and we sought to compare and contrast key features of the negotiation process across several health systems. We focused, in particular, on the criteria for selecting drugs for price negotiation, procedures for negotiation, factors that influence negotiated prices, and how prices are implemented. METHODS: We included four G7 countries in our analysis (Canada, France, Germany, and the United Kingdom [England]), two Benelux countries (Belgium and the Netherlands), and one Scandinavian country (Norway) with long-established frameworks for drug price negotiation. We also analyzed the Veterans Affairs Health System in the United States. For each system, we gathered relevant legislation, government publications, and guidelines to understand negotiation frameworks, and we reached out to key drug price negotiators in each system to conduct semistructured interviews. All interviews were recorded, transcribed, and coded, and data were analyzed based on an internal assessment tool that we developed. FINDINGS: All eight systems negotiate the prices of brand-name prescription drugs soon after approval and rely on formal clinical assessments that compare newly approved drugs with existing therapies. Systems in our study differed on characteristics such as whether the body performing clinical assessments is separate from the negotiating authority, how added health benefit is assessed, whether explicit willingness-to-pay thresholds are employed, and how specific approaches for priority disease areas are taken. CONCLUSIONS: High-income countries around the world adopt different approaches to conducting price negotiations on brand-name drugs but coalesce around a set of practices that will largely be absent from the current Medicare negotiation framework. US policymakers might consider adding some of these characteristics in the future to improve negotiation outcomes.

10.
Artículo en Inglés | MEDLINE | ID: mdl-39284348

RESUMEN

The SrFeO3 nanoparticles doped with 5% and 10% Gd were synthesized using the solution combustion method. The phase formation of the synthesized nanoparticles was confirmed by powder XRD analysis. FESEM and HRTEM were employed to examine the morphology of the samples, revealing well-ordered, agglomerated nanoparticles. EDAX analysis was conducted on all samples, confirming the presence of the desired elements. X-ray photoelectron spectroscopy confirmed the presence of mixed oxidation states of Fe3+ and Fe4+. Magnetization studies, performed using a SQUID magnetometer, showed ferromagnetic behaviour in all samples, with a significant increase in magnetic moment observed with higher Gd doping. The enhanced magnetic moments and reduced coercivity in Gd-doped SrFeO3 suggest that these materials could be suitable for spintronic applications.

11.
Chemphyschem ; : e202400669, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39292526

RESUMEN

There is growing interest in the electronic properties of metalloporphyrins especially in relation to their interactions with other molecular species in their local environment. Here, UV-VIS laser photodissociation spectroscopy in vacuo has been applied to an iron-centred metalloporphyrin (FeTPP+) and its N-aromatic adduct with pyridine (py) to determine the electronic effect of complexation. Both the metalloporphyrin (FeTPP+) and pyridine adduct (FeTPP+⋅py) absorb strongly across the spectral region studied (652-302 nm: 1.91-4.10 eV). Notably, a large blue shift was observed for the dominant Soret band (41 nm) upon complexation (0.47 ± 0.02 eV), indicative of strong pyridine binding. Significant differences in the profiles (i.e. number and position of bands) of the electronic spectra are evident comparing FeTPP+ and FeTPP+⋅py. Time-dependent density functional theory calculations were used to assign the spectra, revealing that the FeIII spin-state flips from S = 3/2 to S = 5/2 upon complexation with pyridine. For FeTPP+, all bright spectral transitions are found to be π-π* in character, with electron density variously distributed across the porphyrin and/or its phenyl substituents. Similar electronic excitations are observed for FeTPP+⋅py, with an additional bright transition which involves charge transfer from the porphyrin to the pyridine moiety.

12.
J Comput Chem ; 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39302059

RESUMEN

A proper understanding of excited state properties of indole derivatives can lead to rational design of efficient fluorescent probes. The optically active L a $$ {L}_a $$ and L b $$ {L}_b $$ excited states of a series of substituted indoles, where a substituent was placed on position four, were calculated using equation of motion coupled cluster and time dependent density functional theory. The results indicate that most substituted indoles have a brighter second excited state corresponding to experimental absorption maxima, but a few with electron withdrawing substituents absorb more on the first excited state. Absorption on the first excited state may increase their fluorescence quantum yield, making them better probes. Electronic structure methods were found to predict the energies of the systems with electron withdrawing substituents more accurately than those with electron donating substituents. The excited states of both states correlated well with electrophilicity, similar to the experimental trends for the absorption maxima. Overall, these computational studies indicate that theory can be used to predict excited state properties of substituted indoles, when the substituent is an electron withdrawing group.

13.
Proc Natl Acad Sci U S A ; 121(39): e2410703121, 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39298481

RESUMEN

The discovery of the quantum Hall effect has established the foundation of the field of topological condensed matter physics. An amazingly accurate quantization of the Hall conductance, now enshrined in quantum metrology, is stable against any reasonable perturbation due to its topological protection. Conversely, the latter implies a form of censorship by concealing any local information from the observer. The spatial distribution of the current in a quantum Hall system is such a piece of information, which, thanks to spectacular recent advances, has now become accessible to experimental probes. It is an old question whether the original and intuitively compelling theoretical picture of the current, flowing in a narrow channel along the sample edge, is the physically correct one. Motivated by recent experiments locally imaging quantized current in a Chern insulator (Bi, Sb)[Formula: see text]Te[Formula: see text] heterostructure [Rosen et al., Phys. Rev. Lett. 129, 246602 (2022); Ferguson et al., Nat. Mater. 22, 1100-1105 (2023)], we theoretically demonstrate the possibility of a broad "edge state" generically meandering away from the sample boundary deep into the bulk. Further, we show that by varying experimental parameters one can continuously tune between the regimes with narrow edge states and meandering channels, all the way to the charge transport occurring primarily within the bulk. This accounts for various features observed in, and differing between, experiments. Overall, our findings underscore the robustness of topological condensed matter physics, but also unveil the phenomenological richness, hidden until recently by the topological censorship-most of which, we believe, remains to be discovered.

14.
Cureus ; 16(8): e66868, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39280522

RESUMEN

The Southern United States (US) bears the highest burden of HIV prevalence in the country, disproportionately affecting African American communities. Despite the proven efficacy of pre-exposure prophylaxis (PrEP) in reducing HIV transmission, its uptake remains suboptimal in this region. This study aimed to identify factors influencing PrEP-prescribing behaviors among primary care providers (PCPs) in the Southern US through the application of the transtheoretical model of behavior change. A cross-sectional survey was conducted among PCPs in 10 Southern states to assess their PrEP-prescribing practices, barriers, and facilitators. The results indicate that non-White PCPs and those practicing in urban and suburban settings are more likely to prescribe PrEP. Key barriers include lack of training, perceived stigma, and systemic issues such as health insurance coverage and time constraints. Significant facilitators are access to prescribing resources, streamlined insurance procedures, and patient motivation. Targeted educational programs and policy changes to address these barriers can enhance PrEP uptake, thereby reducing HIV transmission in high-risk populations. The findings underscore the need for tailored interventions to support PCPs in integrating PrEP into routine care, ultimately contributing to better public health outcomes in the Southern US.

15.
Glob Chang Biol ; 30(9): e17504, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39279652

RESUMEN

Ecosystem responses to disturbance depend on the nature of the perturbation and the ecological legacies left behind, making it critical to understand how climate-driven changes in disturbance regimes modify resilience properties of ecosystems. For coral reefs, recent increases in severe marine heat waves now co-occur with powerful storms, the historic agent of disturbance. While storms kill coral and remove their skeletons, heat waves bleach and kill corals but leave their skeletons intact. Here, we explored how the material legacy of dead coral skeletons modifies two key ecological processes that underpin coral reef resilience: the ability of herbivores to control macroalgae (spatial competitors of corals), and the replenishment of new coral colonies. Our findings, grounded by a major bleaching event at our long-term study locale, revealed that the presence of structurally complex dead skeletons reduced grazing on turf algae by ~80%. For macroalgae, browsing was reduced by >40% on less preferred (unpalatable) taxa, but only by ~10% on more preferred taxa. This enabled unpalatable macroalgae to reach ~45% cover in 2 years. By contrast, herbivores prevented macroalgae from becoming established on adjacent reefs that lacked skeletons. Manipulation of unpalatable macroalgae revealed that the cover reached after 1 year (~20%) reduced recruitment of corals by 50%. The effect of skeletons on juvenile coral growth was contingent on the timing of settlement relative to the disturbance. If corals settled directly after bleaching (before macroalgae colonized), dead skeletons enhanced colony growth by 34%, but this benefit was lost if corals colonized dead skeletons a year after the disturbance once macroalgae had proliferated. These findings underscore how a material legacy from a changing disturbance regime can alter ecosystem resilience properties by disrupting key trophic and competitive interactions that shape post-disturbance community dynamics.


Asunto(s)
Antozoos , Cambio Climático , Arrecifes de Coral , Herbivoria , Algas Marinas , Animales , Antozoos/fisiología , Antozoos/crecimiento & desarrollo , Algas Marinas/fisiología , Algas Marinas/crecimiento & desarrollo
16.
Subst Use Misuse ; : 1-5, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39267262

RESUMEN

OBJECTIVE: Illicitly manufactured fentanyl (IMF) has emerged as a catalyst of the recent drug epidemic in the United States. To devise more targeted and effective prevention and treatment strategies, it is crucial to understand the demographics of the population who consumes IMF and their health and associated substance use risks. Therefore, this study explores the sociodemographic characteristics, health diagnoses, and drug injection practices of individuals reporting IMF use. METHODS: Data were derived from the 2022 National Survey on Drug Use Health, based on a nationally representative sample of non-institutionalized individuals aged 12 and older in the United States. Focusing on 306 adults who reported ever using IMF, we examined their sociodemographic characteristics, health diagnoses, and substance-related behaviors in comparison to adults with a drug use disorder who did not report IMF use, using logistic regression analyses. RESULTS: The majority of U.S. adults reporting IMF use were aged 35-64, male, non-Hispanic White, with a high school education or lower, never married, and had an annual household income below $40,000. Compared to adults with a drug use disorder who did not report IMF use, they were more likely to report heart conditions (AOR = 2.67, 95% CI = 1.29-5.54) and Hepatitis B or C (AOR = 8.35, 95% CI = 4.05-17.02). Nearly half of this group had an opioid use disorder (OUD) in the past year, and 65.7% (95% CI = 56.7-74.8) reported a history of injecting drugs. CONCLUSIONS: To effectively curb the current drug epidemic, incorporating effective treatment for OUD and harm reduction strategies is crucial.

17.
Chembiochem ; : e202400621, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39268627

RESUMEN

Sec-pathway is the main protein secretion pathway in prokaryotes and is essential for their survival. The motor protein SecA is the main coordinator of the pathway in bacteria as it is has evolved to perform multiple tasks, acting like a "swiss army knife", from binding pre-proteins to altering its oligomeric and conformational states. This study focuses on the role of its Preprotein Binding Domain (PBD), which is a key protein module that identified in three conformational states (WO, O and C). A thorough analysis was conducted to identify PBD's inter- and intra-protomeric interactions, highlighting the most significant and conserved ones. Both crystallographic and biophysical data indicate that the WO state is the main during dimerization, while the monomeric structure can adopt all three states. C-tail, StemPBD and 3ß-tipPBD are important elements for the stabilization of different oligomeric and conformational states, as they offer specific interactions. Alterations in the lipophilicity of the StemPBD causes increased proteins dynamics or/and Prl phenotype. In the C state, 3ß-tipPBD interacts and opens the ATPase motor. We hypothesize that this partial opening of the motor with the increased dynamics describes the Prl phenotype.

18.
Commun Phys ; 7(1): 304, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39281307

RESUMEN

X-ray Transient Absorption Spectroscopy (XTAS) is a powerful probe for ultrafast molecular dynamics. The evolution of XTAS signal is controlled by the shapes of potential energy surfaces of the associated core-excited states, which are difficult to directly measure. Here, we study the vibrational dynamics of Raman activated CCl4 with XTAS targeting the C 1s and Cl 2p electrons. The totally symmetric stretching mode leads to concerted elongation or contraction in bond lengths, which in turn induce an experimentally measurable red or blue shift in the X-ray absorption energies associated with inner-shell electron excitations to the valence antibonding levels. The ratios between slopes of different core-excited potential energy surfaces (CEPESs) thereby extracted agree very well with Restricted Open-Shell Kohn-Sham calculations. The other, asymmetric, modes do not measurably contribute to the XTAS signal. The results highlight the ability of XTAS to reveal coherent nuclear dynamics involving  < 0.01 Å atomic displacements and also provide direct measurement of forces on CEPESs.

19.
Biol Psychiatry Glob Open Sci ; 4(6): 100367, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39286525

RESUMEN

Background: Trait mindfulness-the tendency to attend to present-moment experiences without judgment-is negatively correlated with adolescent anxiety and depression. Understanding the neural mechanisms that underlie trait mindfulness may inform the neural basis of psychiatric disorders. However, few studies have identified brain connectivity states that are correlated with trait mindfulness in adolescence, and they have not assessed the reliability of such states. Methods: To address this gap in knowledge, we rigorously assessed the reliability of brain states across 2 functional magnetic resonance imaging scans from 106 adolescents ages 12 to 15 (50% female). We performed both static and dynamic functional connectivity analyses and evaluated the test-retest reliability of how much time adolescents spent in each state. For the reliable states, we assessed associations with self-reported trait mindfulness. Results: Higher trait mindfulness correlated with lower anxiety and depression symptoms. Static functional connectivity (intraclass correlation coefficients 0.31-0.53) was unrelated to trait mindfulness. Among the dynamic brains states that we identified, most were unreliable within individuals across scans. However, one state, a hyperconnected state of elevated positive connectivity between networks, showed good reliability (intraclass correlation coefficient = 0.65). We found that the amount of time that adolescents spent in this hyperconnected state positively correlated with trait mindfulness. Conclusions: By applying dynamic functional connectivity analysis on over 100 resting-state functional magnetic resonance imaging scans, we identified a highly reliable brain state that correlated with trait mindfulness. This brain state may reflect a state of mindfulness, or awareness and arousal more generally, which may be more pronounced in people who are higher in trait mindfulness.


Self-reported mindfulness is negatively associated with adolescent mental illness. The neural bases of differences in self-reported mindfulness are poorly understood. Here, we systematically examined fMRI signatures of self-reported mindfulness in 100 adolescents, with a particular focus on time-varying brain states. After optimizing reliability, we found a state characterized by elevated brain network correlations, and it was positively associated with a specific mindfulness questionnaire that asks questions about emotional awareness and regulation. This state may reflect maintained arousal and awareness in more mindful adolescents.

20.
Front Pharmacol ; 15: 1443555, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39286628

RESUMEN

Objective: This project aims to identify the top 30 drugs most commonly associated with constipation and their signal values within the FDA Adverse Event Reporting System database. Methods: We extracted adverse drug events (ADEs) related to constipation from the FAERS database spanning from January 1, 2004, to September 30, 2023. We compiled the 30 most frequently reported drugs based on the frequency of constipation events. We employed signal detection methodologies to ascertain whether these drugs elicited significant signals, including reporting odds ratio, proportional reporting ratio, multi-item gamma Poisson shrinker, and information component given by the Bayesian confidence propagation neural network. Furthermore, we conducted a time-to-onset (TTO) analysis for drugs generating significant signals using the medians, quartiles, and the Weibull shape parameter test. Results: We extracted a total of 50, 659, 288 ADEs, among which 169,897 (0.34%) were related to constipation. We selected and ranked the top 30 drugs. The drug with the highest ranking was lenalidomide (7,730 cases, 4.55%), with the most prevalent drug class being antineoplastic and immunomodulating agents. Signal detection was performed for the 30 drugs, with constipation risk signals identified for 26 of them. Among the 26 drugs, 22 exhibited constipation signals consistent with those listed on the FDA-approved drug labels. However, four drugs (orlistat, nintedanib, palbociclib, and dimethyl fumarate) presented an unexpected risk of constipation. Ranked by signal values, sevelamer carbonate emerged as the drug with the strongest risk signal [reporting odds ratio (95% CI): 115.51 (110.14, 121.15); PRR (χ2): 83.78 (191,709.73); EBGM (EB05): 82.63 (79.4); IC (IC025): 6.37 (4.70)]. A TTO analysis was conducted for the 26 drugs that generated risk signals, revealing that all drugs exhibited an early failure type. The median TTO for orlistat was 3 days, the shortest of all the drugs, while the median TTO for clozapine was 1,065 days, the longest of all the drugs. Conclusion: Our study provides a list of drugs potentially associated with drug-induced constipation (DIC). This could potentially inform clinicians about some alternative medications to consider when managing secondary causes of constipation or caring for patients prone to DIC, thereby reducing the incidence and mortality associated with DIC.

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