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Asymmetric chemical reactions on the surfaces of colloidal particles are known to propel them into directional motion. The dynamics of such chemical micromotors are sensitive to their local chemical environments, which also continually evolve with the reactions on motor surfaces. This two‐way coupling between the motor dynamics and the local environment may result in complex nonlinear behaviors. As an example, we report that Janus Ag microspheres, which self‐propel in hydrogen peroxide (H2O2), spontaneously reverse their direction of motion two or more times. We hypothesize that two distinct chemical reactions between Ag and H2O2 drive the micromotor in opposite directions, and which reaction dominates depends on the local pH. Interestingly, the local pH near a Ag micromotor oscillates spontaneously in H2O2, likely due to a complex interplay between the kinetics of the reaction between Ag and H2O2 and the diffusion of chemical species. Consequently, the pH‐sensitive Ag micromotor reverses its direction of motion in response to these pH oscillations. This study introduces a new mechanism for regulating the speed and directionality of micromotors, highlights the potential of Ag micromotors in chemical sensing, and sheds new light on the interplay between chemical kinetics and micromotor dynamics. [ABSTRACT FROM AUTHOR]

This article explores the under-researched area of discursive tactics employed in terrorist threat texts that exploit moral values to constantly justify violence, fostering a 'discourse of justification', disaffiliation and conflict. Employing a discursive pragmatic analysis, it delves into the tactics of violent extremists associated with jihadism and far-right ideologies. Utilising the Appraisal framework and the 'moral disaffiliation' strategy, the study uncovers verbal practices shaping a dynamic of justification. Findings reveal threateners' involvement in regulatory discursive functions – manipulation, deontic-retaliation, and boulomaic effect – and practices of ideologically positioning functions – discrediting, blaming, denying and (de)legitimating. The analysis highlights the construction of negative victim individuals and societies while praising the threatener/in-group, anchored predominantly in values of propriety, capacity, valuation and veracity, as the primary dynamic of threatener-victim disalignment. This study contributes insights into threatener profiling, motivations of violence and future research on threat-genre rhetorical structure analysis. [ABSTRACT FROM AUTHOR]

Asymmetric chemical reactions on the surfaces of colloidal particles are known to propel them into directional motion. The dynamics of such chemical micromotors are sensitive to their local chemical environments, which also continually evolve with the reactions on motor surfaces. This two‐way coupling between the motor dynamics and the local environment may result in complex nonlinear behaviors. As an example, we report that Janus Ag microspheres, which self‐propel in hydrogen peroxide (H2O2), spontaneously reverse their direction of motion two or more times. We hypothesize that two distinct chemical reactions between Ag and H2O2 drive the micromotor in opposite directions, and which reaction dominates depends on the local pH. Interestingly, the local pH near a Ag micromotor oscillates spontaneously in H2O2, likely due to a complex interplay between the kinetics of the reaction between Ag and H2O2 and the diffusion of chemical species. Consequently, the pH‐sensitive Ag micromotor reverses its direction of motion in response to these pH oscillations. This study introduces a new mechanism for regulating the speed and directionality of micromotors, highlights the potential of Ag micromotors in chemical sensing, and sheds new light on the interplay between chemical kinetics and micromotor dynamics. [ABSTRACT FROM AUTHOR]

Bleeding events in patients receiving direct oral anticoagulation (DOAC) can be life-threatening even at therapeutic DOAC plasma concentrations, as anticoagulation impairs hemostasis and should therefore be identified immediately after hospital admission. The anticoagulatory effects of DOAC are typically not measurable in standard coagulation tests, such as PT or aPTT. Specific calibrated anti-FXa-tests allow specific drug monitoring, but they are too time-consuming for critical bleeding events and are commonly not available for 24 h/7 days in routine care. However, recent advances in point-of-care (POC) viscoelastic testing (VET) have shown a promising approach for rapid and quantitative detection of DOAC plasma concentrations using the Russell viper venom factor V activator (RVV for FXa-inhibitors) test or the ecarin clotting time (thrombin inhibitors). In acute bleeding situations, direct FXa inhibitors can be reversed by specific antidote andexanet alfa or hemostasis can be improved by prothrombin complex factor concentrates (PCCs). After reversal, confirmation of reversal efficacy is often requested, but no routine assays are currently available. Thus, the emergency management of bleeding DOAC patients is usually "blinded" with regard to reversal efficacy. POC VET laboratory assays might therefore also be helpful for measuring DOAC effects after reversal. We present a case series demonstrating the usefulness of RVV-clotting time post-DOAC reversal with andexanet alfa. [ABSTRACT FROM AUTHOR]

A unified one-dimensional model of an arc plasma in air, between copper electrodes, that includes the change of the gap distance is presented. The occurrence of multiple reversals of the electric field and the anode voltage drop is observed. The evolution of the spatial distribution of the electron and heavy particle temperatures with the gap distance and the opening speed is also studied. The model quantitatively predicts a number of plasma properties under conditions that are relevant to the contact separation in low-voltage switching devices. [ABSTRACT FROM AUTHOR]

Our previous study showed that pyridoxine 5'-phosphate oxidase (PNPO) is a tissue biomarker of ovarian cancer (OC) and has a prognostic implication but detailed mechanisms remain unclear. The current study focused on PNPO-regulated lysosome/autophagy-mediated cellular processes and the potential role of PNPO in chemoresistance. We found that PNPO was overexpressed in OC cells and was a prognostic factor in OC patients. PNPO significantly promoted cell proliferation via the regulation of cyclin B1 and phosphorylated CDK1 and shortened the G2M phase in a cell cycle. Overexpressed PNPO enhanced the biogenesis and perinuclear distribution of lysosomes, promoting the degradation of autophagosomes and boosting the autophagic flux. Further, an autolysosome marker LAMP2 was upregulated in OC cells. Silencing LAMP2 suppressed cell growth and induced cell apoptosis. LAMP2-siRNA blocked PNPO action in OC cells, indicating that the function of PNPO on cellular processes was mediated by LAMP2. These data suggest the existence of the PNPO-LAMP2 axis. Moreover, silencing PNPO suppressed xenographic tumor formation. Chloroquine counteracted the promotion effect of PNPO on autophagic flux and inhibited OC cell survival, facilitating the inhibitory effect of PNPO-shRNA on tumor growth in vivo. Finally, PNPO was overexpressed in paclitaxel-resistant OC cells. PNPO-siRNA enhanced paclitaxel sensitivity in vitro and in vivo. In conclusion, PNPO has a regulatory effect on lysosomal biogenesis that in turn promotes autophagic flux, leading to OC cell proliferation, and tumor formation, and is a paclitaxel-resistant factor. These data imply a potential application by targeting PNPO to suppress tumor growth and reverse PTX resistance in OC. [ABSTRACT FROM AUTHOR]

The concept and analysis of integrating membrane distillations (MD) with reversal once-through Multistage Flash (RV-MSF) desalination is presented. The analysis is based on numerical simulation. The MD vessels are integrated into the terminal ends of the RV-MSF system to leverage the thermal energy associated with these terminal streams. Hybridisation at the last MSF stage, i.e. by replacing the brine cooler, contributes marginally to the overall production rate which amounts to 2%. However, it is found that hybridisation at stage one, i.e. utilising the energy of the MSF reject brine can increase the overall production rate by 65%. For seawater feed temperature of 80 oC and 24 MSF stages, 5 MD vessels in series can be integrated with the RV-MSF process. This ultimate hybridisation helped improve the recovery ratio from 7 to 23%, decreasing the specific cooling water requirement from 23 to 12 kg/kg and reducing the specific energy consumption from 129 to 41 kWh/m3 with respect to the stand-alone RV-MSF system. However, this achievement incurs an additional specific area for heat transfer which increased from 29 to 65 m2/(kg/s). This is because a large number of MD modules are incorporated into the hybridisation. [ABSTRACT FROM AUTHOR]

Purpose: Weight thresholds have historically determined timing of enterostomy closure (EC) in premature neonates. Recent evidence suggests that neonates less than 2 kg (L2K) can safely undergo EC. We evaluate our single-center experience with performing EC in preterm neonates at L2K versus greater than 2 kg (G2K) at time of EC. Methods: A retrospective review of neonates who underwent EC from January 2018 to 2020 was performed. Neonates who were greater than 90 days at initial operation were excluded. Demographics, clinical characteristics including gestational age (GA) and birth weight (BW), operative reports, and outcomes were reviewed. We compared 30-day complications between neonates who underwent EC at L2K and G2K. We also compared time to full feeds (FF) and postoperative length of stay (LOS). Results: Twenty-four neonates were included: 11 L2K and 13 G2K. The median GA and BW was 25.9 weeks (IQR 2.89) and 805 g (IQR 327), respectively. The most common intraoperative diagnosis during index operation was spontaneous perforation (70%), followed by necrotizing enterocolitis (8.69%). There were no significant differences in GA, BW, or diagnosis, between the L2K versus G2K cohort. We found no difference in complication rates, time to FF (12 days versus 10 days, P =.89), or postoperative LOS (31 days versus 36.5 days, P =.76) between patients who underwent EC at L2K versus G2K, respectively. Conclusion: Although weight gain may be an important indicator of perioperative nutrition status, this study shows that weight alone should not preclude otherwise appropriate patients from undergoing EC. [ABSTRACT FROM AUTHOR]

We document considerable cross-investor variation in survey expectations about aggregate stock market returns. Although most investors are extrapolators who expect higher returns after a good market performance, some are contrarians who expect lower returns after a good performance. More notably, compared with extrapolators, contrarians have less persistent expectations that are corrected more quickly. We then develop a dynamic equilibrium model accounting for these differences in expectations and find that the equilibrium stock price exhibits short-term momentum and long-term reversal as in the data. Furthermore, we test the key predictions of our model linking the observable differences in extrapolators' and contrarians' expectations to aggregate stock market momentum and future stock performance and find supportive evidence for our model mechanism. This paper was accepted by Lukas Schmid, finance. Supplemental Material: The data files are available at https://doi.org/10.1287/mnsc.2023.4960. [ABSTRACT FROM AUTHOR]

Momentum profits collapse and reversal occurs when preceding market volatility is relatively high. Based on these intertemporal patterns, we implement an investment strategy that switches from momentum to reversal when volatility is high. The proposed switching strategy has two advantages over scaled momentum strategies: (1) the leverage factor is constant, and (2) no ex post information is used to control volatility. Additionally, in US stock market tests, the switching strategy eliminates losses due to momentum crashes, a problem that has plagued momentum strategies in practice. Further evidence confirms that the switching strategy is successful in other developed and emerging stock markets. [ABSTRACT FROM AUTHOR]

Abstract Bleeding events in patients receiving direct oral anticoagulation (DOAC) can be life-threatening even at therapeutic DOAC plasma concentrations, as anticoagulation impairs hemostasis and should therefore be identified immediately after hospital admission. The anticoagulatory effects of DOAC are typically not measurable in standard coagulation tests, such as PT or aPTT. Specific calibrated anti-FXa-tests allow specific drug monitoring, but they are too time-consuming for critical bleeding events and are commonly not available for 24 h/7 days in routine care. However, recent advances in point-of-care (POC) viscoelastic testing (VET) have shown a promising approach for rapid and quantitative detection of DOAC plasma concentrations using the Russell viper venom factor V activator (RVV for FXa-inhibitors) test or the ecarin clotting time (thrombin inhibitors). In acute bleeding situations, direct FXa inhibitors can be reversed by specific antidote andexanet alfa or hemostasis can be improved by prothrombin complex factor concentrates (PCCs). After reversal, confirmation of reversal efficacy is often requested, but no routine assays are currently available. Thus, the emergency management of bleeding DOAC patients is usually “blinded” with regard to reversal efficacy. POC VET laboratory assays might therefore also be helpful for measuring DOAC effects after reversal. We present a case series demonstrating the usefulness of RVV-clotting time post-DOAC reversal with andexanet alfa.

Factor Ⅺ (FⅪ) plays a major role in thrombus amplification and an ancillary role in hemostasis. This differential contribution is expected to provide new ideas for the prevention and treatment of thrombotic diseases by targeting FⅪ as a potentially safer anticoagulation strategy. Currently, an increasing number of FⅪ inhibitors are entering phaseⅢ clinical trials, and although these inhibitors showed promising clinical potential, the strategies for monitoring and reversing the effects of these inhibitors remain unclear, which poses new challenges for laboratory monitoring and clinical practice. This review, based on the physiological function of FⅪ and FⅪ inhibitors under study, systematically explored the laboratory evidence of coagulation activity linked to these inhibitors, summarized potential methods of reversal in combination with the treatment protocols of inherited FⅪ deficiency, which provided certain references for the development of clinical treatment protocols and reversal strategies.

Norhayati Mustafa Khalid,1 Pavapriya Ponvel,1 Azianah Mohamad Ibrahim,1 A’isyah Mohd Safien,1 Nurul Hidayah Md Fadzil,1 Devinder Kaur Ajit Singh,1 Arimi Fitri Mat Ludin,1 Norhayati Ibrahim,1 Ponnusamy Subramaniam,1 Hasnah Haron,1 Roslee Rajikan,1 Divya Vanoh,2 Suzana Shahar1 1Center for Healthy Aging and Wellness, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia; 2Dietetics Programme, School of Health Sciences, Universiti Sains Malaysia, Kelantan, MalaysiaCorrespondence: Suzana Shahar, Center for Healthy Aging and Wellness, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur, 50300, Malaysia, Tel +60 392897163, Email suzana.shahar@ukm.edu.myPurpose: There is a limited availability of multidomain interventions that target cognitive frailty. Thus, the aim of the present study was to develop and evaluate the content validity and acceptance of the multidomain intervention module to reverse cognitive frailty among older adults (iAGELESS).Patients and Methods: This study was conducted in two phases: Phase I included the development of the multidomain intervention module iAGELESS and evaluation of content validity, while Phase II consisted of evaluating the acceptance of the module among 18 healthcare and social care providers, 13 older adults with cognitive frailty, and 13 caregivers. Content validity index (CVI) was used to quantify the content validity. Respondents completed a questionnaire which consisted of information on sociodemographic, followed by module acceptance evaluation with respect to content, terminologies, and graphics. The data was then analyzed descriptively.Results: A multidomain intervention module, iAGELESS was developed. The module was found to have appropriate content validity (overall CVI = 0.83). All the caregivers, 92% of older adults with cognitive frailty and 83% of healthcare and social care providers were satisfied with the overall content of the module. More than 50% of those who accepted the module had satisfactory consensus on the ease of the terminologies, length of sentences, pictures, information, color, and font size included in the module.Conclusion: The iAGELESS module demonstrated good content validity and was well accepted, thus warranting its utilization in future studies to determine its effectiveness in reversing cognitive frailty among older adults.Keywords: aging, cognitive frailty, multidomain intervention module, older adults, reversal

Objective: Andexanet alfa is approved for the reversal of life-threatening or uncontrolled bleeding due to factor-Xa inhibitors. Data are limited on outcomes for patients who receive both andexanet alfa and 4-factor prothrombin complex concentrate (4F-PCC). The aim of this case series is to evaluate the safety and efficacy outcomes in patients receiving the two agents in combination. Methods: Electronic medical records of patients who received both 4F-PCC and andexanet alfa for nontraumatic intracranial hemorrhage from January 2019 to March 2022 were retrospectively reviewed. Hemostatic efficacy and complications related to concurrent use of 4F-PCC with andexanet alfa were documented. Results: Nine patients received 4F-PCC and andexanet alfa for reversal of factor Xa inhibitor-associated intracranial bleeding, eight of whom required reversal of apixaban. Of these nine patients, five patients died within 28 days for a 56% incidence of mortality. The average time from 4F-PCC administration to andexanet alfa administration was 3 hours and 9 minutes. Most doses of andexanet alfa were given for concern for bleed expansion after 4F-PCC administration. Hemostatic efficacy based on stability of repeat computed tomography scans post-administration of both agents was found in six patients (66.67%), with a 55.56% n incidence of thromboembolism, including two pulmonary embolisms, two deep vein thromboses, and one renal artery thrombosis. Conclusion : Risks and benefits should be weighed to determine if there is benefit to adding andexanet alfa to 4F-PCC in patients with incomplete hemostasis and life-threatening hemorrhage. The combination of andexanet alfa and 4F-PCC may increase the risk of thrombotic complications without improving mortality. [ABSTRACT FROM AUTHOR]

This paper explores the distribution and semantics of the reversative affix un- and the restitutive affix re-, and overall makes a new proposal about the lexical semantics of verbs. I argue that these affixes tell a story of derivational morphology that is based not on categorization of verbs into neat aspectual and decompositional classes, but on the result of the verb's action on the object and whether or not such a result state permits reversal and restitution. The argument structure of these affixes shows us that morphology interacts with semantics in a true compositional sense, whereby the affectedness of the object is a crucial factor in determining compatibility and composition. I propose an approach to verb meaning that encodes this important information as outcomes: the lifespan properties of the object after the action occurs on it. I propose, formulating the Verb-Root-Outcomes framework, that all verb roots come equipped with sets of outcomes. A wide array of verbs that have been classified as 'change-of-state' are shown to have different sub-classes based on the shape of the outcome set, and this also allows a formal definition of what 'potential' change could mean. The affixes un- and re- are modeled as result-state modifiers, which are sensitive to the outcomes of the action of the verb stem they attach to, and only attach when their presuppositions about the state of the object are met. Apart from directly comparing reversal and restitution with the same formal notion of equivalence, this approach also allows a transparent representation of event decomposition, whereby change in the object is able to be tracked at a granular level and its importance in determining the success of morphological derivations highlighted. This theory argues for compositional semantic interpretation at a sub-lexical level, while also showing how sentential and pragmatic factors affect verb meaning and derivational affixation. [ABSTRACT FROM AUTHOR]

In the sedimentary strata dating of estuarial coastal areas, it is often found that there is phenomenon of time-reversal in strata. The seabed sediments could be liquefied under storm waves. A laboratory wave flume experiment demonstrated that storm-induced liquefaction deposits are formed by the oscillations of liquefied sediments. In this paper, the particle size distribution and 210Pbex specific activity of the sediment samples from the liquefaction disturbed zone and adjacent stable zone of the Yellow River Delta were tested. The stratigraphic divisions based on storm liquefaction deposit sequence can effectively explain the vertical changes in particle size and 210Pbex specific activity. Due to the differentiation of particles during the storm induced liquefaction, coarse and fine particles regrouped, which could explain the phenomenon of time-reversal in dating data. [ABSTRACT FROM AUTHOR]

With the development of nanotechnology, it is found that the chiral semiconductor nanocrystals have vast potential applications in many different fields, such as biological labels, chiral analysis and detectors, enantioselective separation, gene editing, spin electronic devices, and so on. However, the study of their stability is rare. Here, we report the stability of chiral wurtzite CdSe quantum rods (QRs) and nanoplatelets (NPLs) with conventional chiral ligands of cysteine kept in an ambient atmosphere. The chiral QRs show specific stability in water solvents; however, that of the chiral NPLs is weak, with completely reverse chiroptical signs in just 90 min. The combination of experimental proofs and theoretical results reveals that the reversed optical activities come from the switch of electronic transition dipole moments of chiral CdSe surfaces. Our study helps to survey the construction of more stable chiral semiconductor nanomaterials, which is the key to improving their applications. [ABSTRACT FROM AUTHOR]

AbstractOne of the commonly used single-case experimental designs (SCEDs) in education research is the ABAB design, commonly referred to as reversal design. This design is applicable when the studied behavior is reversible (i.e., reverses to baseline levels when the intervention is withdrawn) and it allows for a within-unit replication of the “basic effect”, that is, a comparison between two adjacent conditions (with and without an active intervention). Methodologically, one of its strengths is to provide three phase change moments to demonstrate experimental control. However, the withdrawal of the intervention (i.e., the comparison between the first intervention phase and the second baseline phase) has not received sufficient attention in the SCED literature. The aim of the current text is to propose quantifications that enable using the information from the withdrawal. Specifically, the quantifications allow for assessing the degree to which withdrawing the intervention leads to initial baseline levels as well as incorporating the reversal in an overall effect size. The proposals are illustrated with several real educational science data sets, including both within-unit analysis and replication of the ABAB design across units, and representing different degrees of reversal of the target behavior when the intervention is withdrawn. [ABSTRACT FROM AUTHOR]

In recent years, the evolution of antibiotic resistance has led to the inefficacy of several antibiotics, and the reverse of resistance was a novel method to solve this problem. We previously demonstrated that matrine (Mat) and berberine hydrochloride (Ber) had a synergistic effect against multidrug-resistant Escherichia coli (MDREC). This study aimed to demonstrate the effect of Mat combined with Ber in reversing the resistance of MDREC. The MDREC was sequenced passaged in the presence of Mat, Ber, and a combination of Mat and Ber, which did not affect its growth. The reverse rate was up to 39.67% after MDREC exposed to Mat + Ber for 15 days. The strain that reversed resistance was named drug resistance reversed E. coli (DRREC) and its resistance to ampicillin, streptomycin, gentamicin, and tetracycline was reversed. The MIC of Gentamicin Sulfate (GS) against DRREC decreased 128-fold to 0.63 µg/mL, and it was stable within 20 generations. Furthermore, the susceptible phenotype of DRREC remained stable within 20 generations, as well. The LD50 of DRREC for chickens was 8.69 × 109 CFU/mL. qRT-PCR assays revealed that the transcript levels of antibiotic-resistant genes and virulence genes in the DRREC strain were significantly lower than that in the MDREC strain (P < 0.05). In addition, GS decreased the death, decreased the bacterial loading in organs, alleviated the injury of the spleen and liver, and decreased the cytokine levels in the chickens infected by the DRREC strain. In contrast, the therapeutic effect of GS in chickens infected with MDREC was not as evident. These findings suggest that the combination of Mat and Ber has potential for reversing resistance to MDREC. [ABSTRACT FROM AUTHOR]

Purpose: There is a limited availability of multidomain interventions that target cognitive frailty. Thus, the aim of the present study was to develop and evaluate the content validity and acceptance of the multidomain intervention module to reverse cognitive frailty among older adults (iAGELESS). Patients and Methods: This study was conducted in two phases: Phase I included the development of the multidomain intervention module iAGELESS and evaluation of content validity, while Phase II consisted of evaluating the acceptance of the module among 18 healthcare and social care providers, 13 older adults with cognitive frailty, and 13 caregivers. Content validity index (CVI) was used to quantify the content validity. Respondents completed a questionnaire which consisted of information on sociodemographic, followed by module acceptance evaluation with respect to content, terminologies, and graphics. The data was then analyzed descriptively. Results: A multidomain intervention module, iAGELESS was developed. The module was found to have appropriate content validity (overall CVI = 0.83). All the caregivers, 92% of older adults with cognitive frailty and 83% of healthcare and social care providers were satisfied with the overall content of the module. More than 50% of those who accepted the module had satisfactory consensus on the ease of the terminologies, length of sentences, pictures, information, color, and font size included in the module. Conclusion: The iAGELESS module demonstrated good content validity and was well accepted, thus warranting its utilization in future studies to determine its effectiveness in reversing cognitive frailty among older adults. [ABSTRACT FROM AUTHOR]

Purpose: There is a lack of evidence for treatment of some conditions including complication management, suboptimal initial weight loss, recurrent weight gain, or worsening of a significant obesity complication after one anastomosis gastric bypass (OAGB). This study was designed to respond to the existing lack of agreement and to provide a valuable resource for clinicians by employing an expert-modified Delphi consensus method. Methods: Forty-eight recognized bariatric surgeons from 28 countries participated in the modified Delphi consensus to vote on 64 statements in two rounds. An agreement/disagreement among ≥ 70.0% of the experts was regarded to indicate a consensus. Results: A consensus was achieved for 46 statements. For recurrent weight gain or worsening of a significant obesity complication after OAGB, more than 85% of experts reached a consensus that elongation of the biliopancreatic limb (BPL) is an acceptable option and the total bowel length measurement is mandatory during BPL elongation to preserve at least 300–400 cm of common channel limb length to avoid nutritional deficiencies. Also, more than 85% of experts reached a consensus on conversion to Roux-en-Y gastric bypass (RYGB) with or without pouch downsizing as an acceptable option for the treatment of persistent bile reflux after OAGB and recommend detecting and repairing any size of hiatal hernia during conversion to RYGB. Conclusion: While the experts reached a consensus on several aspects regarding revision/conversion surgeries after OAGB, there are still lingering areas of disagreement. This highlights the importance of conducting further studies in the future to address these unresolved issues. [ABSTRACT FROM AUTHOR]

The activation of pregnane X receptor (PXR) or peroxisome proliferator-activated receptor α (PPARα) can induce liver enlargement. Recently, we reported that PXR or PPARα activation-induced hepatomegaly depends on yes-associated protein (YAP) signaling and is characterized by hepatocyte hypertrophy around the central vein area and hepatocyte proliferation around the portal vein area. However, it remains unclear whether PXR or PPARα activation-induced hepatomegaly can be reversed after the withdrawal of their agonists. In this study, we investigated the regression of enlarged liver to normal size following the withdrawal of PCN or WY-14643 (typical agonists of mouse PXR or PPARα) in C57BL/6 mice. The immunohistochemistry analysis of CTNNB1 and KI67 showed a reversal of hepatocyte size and a decrease in hepatocyte proliferation after the withdrawal of agonists. In details, the expression of PXR or PPARα downstream proteins (CYP3A11, CYP2B10, ACOX1, and CYP4A) and the expression of proliferation-related proteins (CCNA1, CCND1, and PCNA) returned to the normal levels. Furthermore, YAP and its downstream proteins (CTGF, CYR61, and ANKRD1) also restored to the normal states, which was consistent with the change in liver size. These findings demonstrate the reversibility of PXR or PPARα activation-induced hepatomegaly and provide new data for the safety of PXR and PPARα as drug targets. • PXR or PPARα activation-induced hepatomegaly is reversible. • The hepatocyte size and proliferation return to normal state after the reversal. • Protein levels altered by PXR or PPARα activation are restored after the reversal. [ABSTRACT FROM AUTHOR]

Non-activated four-factor prothrombin complex concentrate (4 F-PCC) has emerged as the preferred reversal strategy for patients on warfarin with life-threatening bleeding. Current dosing recommendations for 4 F-PCC require pre-treatment international normalized ratio (INR) and bodyweight values, resulting in ordering and administration delays. Studies have shown that alternative dosing regimens are safe and efficacious. This retrospective, single-center, pre- and post-protocol analysis was conducted to assess the efficacy of a pharmacist driven modified fixed-dose 4 F-PCC regimen versus package insert weight- and INR-based dosing regimen for warfarin reversal. The primary outcome was achievement of INR less than two. Secondary outcomes included dose and cost of 4 F-PCC, a time analysis, incidence of concomitant vitamin K administration, and incidence of thrombosis within seven days of 4 F-PCC. There were 195 patients included in the analysis, with 74 in the pre-cohort and 121 in the post-cohort. Baseline characteristics were similar between cohorts with the most common indication for warfarin use being atrial fibrillation (48.6% versus 47.1%) and reversal being intracerebral hemorrhage (68.9% versus 43.0%). Achievement of the primary endpoint occurred in 92% versus 95% (p = 0.097) of patients. A statistically significant difference was seen between cohorts regarding median dose and cost of 4 F-PCC administered (p < 0.001). Eleven thromboembolic events occurred with three events in the pre-cohort and eight events in the post-cohort (p = 0.453). A fixed-dose of 1500IU of 4 F-PCC was effective in reversing INR to less than two in most patients regardless of reversal indication with minimal thrombotic risks. Highlights: No consensus exists for the ideal dosing scheme for 4 F-PCC for warfarin reversal. We describe our experience with a pharmacist driven modified-fixed dose 4 F-PCC protocol for warfarin reversal. No difference in reversal of INR < 2 was seen between package-insert weight and INR based dosing compared to modified fixed-dose 4 F-PCC dosing for warfarin reversal. Future research regarding to establish non-inferiority between fixed-dose and package-insert dosing is warranted. [ABSTRACT FROM AUTHOR]

This document is a letter published in the journal Systematic Reviews. The letter discusses the optimal dosage of adamgammadex, a reversal agent, for the reversal of rocuronium-induced neuromuscular block. The authors conducted a meta-analysis of three randomized controlled trials comparing different doses of adamgammadex and sugammadex for the reversal of rocuronium-induced neuromuscular blockade. The results suggest that both doses of adamgammadex (4 mg/kg and 6 mg/kg) are effective in reversing neuromuscular blockade, providing flexibility in dosing options for anesthesiologists and surgeons. However, further large-scale trials are needed to confirm these findings and evaluate the safety profile of adamgammadex at different doses. [Extracted from the article]

Abstract The use of anticoagulants has become more frequent due to the progressive aging population and increased thromboembolic events. Consequently, the proportion of anticoagulant-associated intracerebral hemorrhage (AAICH) in stroke patients is gradually increasing. Compared with intracerebral hemorrhage (ICH) patients without coagulopathy, patients with AAICH may have larger hematomas, worse prognoses, and higher mortality. Given the need for anticoagulant reversal and resumption, the management of AAICH differs from that of conventional medical or surgical treatments for ICH, and it is more specific. Understanding the pharmacology of anticoagulants and identifying agents that can reverse their effects in the early stages are crucial for treating life-threatening AAICH. When patients transition beyond the acute phase and their vital signs stabilize, it is important to consider resuming anticoagulants at the right time to prevent the occurrence of further thromboembolism. However, the timing and strategy for reversing and resuming anticoagulants are still in a dilemma. Herein, we summarize the important clinical studies, reviews, and related guidelines published in the past few years that focus on the reversal and resumption of anticoagulants in AAICH patients to help implement decisive diagnosis and treatment strategies in the clinical setting.

Background: There are no randomized trials comparing andexanet alfa and 4 factor prothrombin complex concentrate (4F-PCC) for the treatment of factor Xa inhibitor (FXa-I)-associated bleeds, and observational studies lack important patient characteristics. We pursued this study to demonstrate the feasibility of acquiring relevant patient characteristics from electronic health records. Secondarily, we explored outcomes in patients with life-threatening FXa-I associated bleeds after adjusting forthese variables.Methods: We conducted a multicenter, chart review of 100 consecutive adult patients with FXa-I associated intracerebral hemorrhage (50) or gastrointestinal bleeding (50) treated with andexanet alfa or 4F-PCC. We collected demographic, clinical, laboratory, and imaging data including time from last factor FXa-I dose and bleed onset.Results: Mean (SD) age was 75 (12) years; 34% were female. Estimated time from last FXa-I dose to bleed onset was present in most cases (76%), and patients treated with andexanet alfa and 4F-PCC were similar in baseline characteristics. Hemostatic efficacy was excellent/good in 88% and 76% of patients treated with andexanet alfa and 4F-PCC, respectively (P = 0.29). Rates of thrombotic events within 90 days were 14% and 16% in andexanet alfa and 4F-PCC patients, respectively (P = 0.80). Survival to hospital discharge was 92% and 76% in andexanet alfa and 4F-PCC patients, respectively (P = 0.25). Inclusion of an exploratory propensity score and treatment in a logistic regression model resulted in an odds ratio in favor of andexanet alfa of 2.01 (95% confidence interval 0.67–6.06) for excellent/good hemostatic efficacy, although the difference was not statistically significant.Conclusion: Important patient characteristics are often documented supporting the feasibility of a large observational study comparing real-life outcomes in patients with FXa-I-associated bleeds treated with andexanet alfa or 4F-PCC. The small sample size in the current study precluded definitive conclusions regarding the safety and efficacy of andexanet alfa or 4F-PCC in FXa-I-associated bleeds.

Motivated by the deteriorating performance of traditional cross-sectional momentum strategies in commodity futures markets, we propose to resurrect momentum by incorporating autocorrelation information into the asset selection process. Put differently, we introduce measures of short and long memory (variance ratios and Hurst coefficients, respectively) telling us whether past winners and losers are likely to persist or not. Our empirical findings suggest that a memory-enhanced momentum strategy based on variance ratios significantly outperforms traditional momentum in terms of reward and risk, effectively prevents momentum crashes and is not bound to the movement of the overall commodity market. The strategy returns cannot be explained by typical factor portfolios and macroeconomic variables. They are also robust to alternative data sets, transaction costs and data snooping. In comparison, Hurst coefficients carry less investment-relevant information and cannot outperform variance ratios in terms of risk premia and investment alpha. [ABSTRACT FROM AUTHOR]

The use of anticoagulants has become more frequent due to the progressive aging population and increased thromboembolic events. Consequently, the proportion of anticoagulant-associated intracerebral hemorrhage (AAICH) in stroke patients is gradually increasing. Compared with intracerebral hemorrhage (ICH) patients without coagulopathy, patients with AAICH may have larger hematomas, worse prognoses, and higher mortality. Given the need for anticoagulant reversal and resumption, the management of AAICH differs from that of conventional medical or surgical treatments for ICH, and it is more specific. Understanding the pharmacology of anticoagulants and identifying agents that can reverse their effects in the early stages are crucial for treating life-threatening AAICH. When patients transition beyond the acute phase and their vital signs stabilize, it is important to consider resuming anticoagulants at the right time to prevent the occurrence of further thromboembolism. However, the timing and strategy for reversing and resuming anticoagulants are still in a dilemma. Herein, we summarize the important clinical studies, reviews, and related guidelines published in the past few years that focus on the reversal and resumption of anticoagulants in AAICH patients to help implement decisive diagnosis and treatment strategies in the clinical setting. [ABSTRACT FROM AUTHOR]

Investigation is necessary to figure out magnetization dynamics at high temperatures due to the low power requirement for heat-assisted magnetic recording technology. The Landau-Lifshitz-Gilbert equation was employed to assess the dynamic of magnetization in perpendicular magnetic-dots at elevated temperatures, considering the thermal contribution to the effective field. The simulated perpendicular magnetic-dot has a 50×50 nm² surface area with thicknesses of 10 nm, 50 nm, and 100 nm. This study reveals that the probability of magnetization reversal and the threshold field in the thermally-assisted magnetic reversal process of a magnetic dot is influenced by the thickness and writing temperature. Below the Curie point, as sample thickness increases, demagnetization energy increases, requiring a larger external magnetic field for magnetization reversal. For the thicker sample, the magnitude of the writing field decreases as the temperature increases, which corresponds to temperature-dependent magnetization. Meanwhile, the optimum writing field is obtained below the Curie point. The magnetic-dot with 100 nm of thickness has an effective writing temperature of 739.7 K with a corresponding writing field is 250 Oe while its reversal probability at zero magnetic field is up to 0.2. Magnetic-dot thickness affects magnetization reversal probability due to domain wall propagation mechanisms during magnetic switching that result from the demagnetization factor. Moreover, as the temperature approaches the Curie temperature, the probability of zero-field magnetization reversal in the absence of an external magnetic field is observed to escalate which has a direct impact on the writing field magnitude. It was found that the effective writing temperature is below the Curie temperature, which allows several hundred Oersted of the writing field. [ABSTRACT FROM AUTHOR]

Purpose: In the past, preinjury direct oral anticoagulant (DOAC) intake has led to delays in time to surgery (TTS) in patients with proximal femur fractures and delays in surgery have been associated with impaired outcomes. Although healthcare institutions/federal committees have set rules for treatment within 24 h of injury, comprehensive guidelines for the perioperative management of these patients, in particular when on preinjury DOACs, are still lacking. This contribution aims to summarize the current evidence on the safe time window for surgery in patients with proximal femur fractures on preinjury DOACs and to outline therapeutic options if emergency DOAC reversal becomes necessary. Methods: Narrative review based upon selective review of the pertinent literature. Results: For the majority of patients with proximal femur fractures and on preinjury DOACs, early surgery appears safe as soon as medical clearance has been obtained. There may be an increase in the need for blood products but with data not yet conclusive. Work-up including assessment of remaining anticoagulant activity and potential reversal should be restricted to patients at risk for bleeding complications, in particular in the presence of renal/hepatic impairment. Methodology for rapid assessment of DOACs including quantitative/qualitative concentration levels is work in progress. In the case of bleeding, rapidly acting reversal agents are available. Conclusion: Preinjury DOAC use should not routinely delay surgery in patients with proximal femur fractures. [ABSTRACT FROM AUTHOR]

Historically, many canvas paintings were infused with wax–resin mixtures that have discolored over time, distorting the aesthetics of the work, limiting treatment options, and introducing unstable materials into the object. Removal of the wax–resin is often desirable, but before works of art can be treated, a protocol to evaluate the efficacy of the treatment must be established. A mock-up painting was infused with a known amount of a wax–resin mixture made from beeswax and dammar; this material was then extracted through six intervals of exposure to solvent-loaded and dry sheets of Evolon® CR, a non-woven textile with a high sorbent capacity. Samples from the Evolon® CR sheets from each extraction round were analyzed using thermal separation probe gas chromatography–mass spectrometry (TSP-GC/MS). Normalization of peak areas related to beeswax and dammar to those of Evolon® CR revealed the relative amount of wax and resin removed throughout the extraction. The data show that, under these test conditions, the beeswax and dammar appear to be extracted with the same relative efficiency, information that cannot be provided through UV-induced visible fluorescence imaging of the Evolon® CR sheets or weight data alone, but which is critical to capture as it has implications for treatment success and the long-term stability of an artwork. [ABSTRACT FROM AUTHOR]

Venous thromboembolism (VTE) and stroke carry significant mortality and morbidity in cancer patients. Direct oral anticoagulants (DOACs) have been demonstrated to be effective for the treatment of VTE and prevention of stroke in atrial fibrillation (AF). Bleeding rates are variable and are based on the cancer type and the patient's specific risk factors. There are approved specific antidotes for DOAC-associated bleeding. Other strategies are available for bleeding reversal, including the use of prothrombin complex concentrate (PCC). No randomized studies have compared head-to-head the efficacy and safety of reversal agents. We aim to examine the safety and effectiveness of hemostatic agents in cancer patients with DOAC-related major bleeding. A retrospective chart review study of patients at MD Anderson Cancer Center with DOAC-related major bleeding between 2014 and 2019. Bleeding severity and clinical hemostasis were described based on ISTH guidelines and the Sarode criteria, respectively. The rates of thrombotic complications and mortality at 30-day from the index bleeding event were described. We identified 23 patients with DOAC-related major bleeding; 14 patients received PCC and 9 patients received andexanet alfa. The most common sites of bleeding were the gastrointestinal tract and intracranial. Effective hemostasis and 30-day mortality were similar to reported results from other reports of outcomes of reversal agents for DOAC related-bleeding in non-cancer patients. One patient in each treatment group experienced a thrombotic event. Further larger scale studies are needed to confirm our findings in cancer patients. [ABSTRACT FROM AUTHOR]

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Aim: Several methods for assessing anastomotic integrity have been proposed, but the best is yet to be defined. The aim of this study was to compare the different methods to assess the integrity of colorectal anastomosis prior to ileostomy reversal. Method: A retrospective cohort analysis on patients between 1 January 2010 and 31 December 2020 with a defunctioning stoma for middle and low rectal anterior resection was performed. A propensity score matching comparison between patients who underwent proctoscopy alone and patients who underwent proctoscopy plus any other preoperative method to assess the integrity of colorectal anastomosis prior to ileostomy reversal (transanal water‐soluble contrast enema via conventional radiology, transanal water‐soluble contrast enema via CT, and magnetic resonance) was performed. Results: The analysis involved 1045 patients from 26 Italian referral colorectal centres. The comparison between proctoscopy alone versus proctoscopy plus any other preoperative tool showed no significant differences in terms of stenoses (p = 0.217) or leakages (p = 0.103) prior to ileostomy reversal, as well as no differences in terms of misdiagnosed stenoses (p = 0.302) or leakages (p = 0.509). Interestingly, in the group that underwent proctoscopy and transanal water‐soluble contrast enema the comparison between the two procedures demonstrated no significant differences in detecting stenoses (2 vs. 0, p = 0.98), while there was a significant difference in detecting leakages in favour of transanal water‐soluble contrast enema via CT (3 vs. 12, p = 0.03). Conclusions: We can confirm that proctoscopy alone should be considered sufficient prior to ileostomy reversal. However, in cases in which the results of proctoscopy are not completely clear or the surgeon remains suspicious of an anastomotic leakage, transanal water‐soluble contrast enema via CT could guarantee its detection. [ABSTRACT FROM AUTHOR]

A major challenge for neuroscience, public health, and evolutionary biology is to understand the effects of scarcity and uncertainty on the developing brain. Currently, a significant fraction of children and adolescents worldwide experience insecure access to food. The goal of our work was to test in mice whether the transient experience of insecure versus secure access to food during the juvenile-adolescent period produced lasting differences in learning, decision-making, and the dopamine system in adulthood. We manipulated feeding schedules in mice from postnatal day (P)21 to P40 as food insecure or ad libitum and found that when tested in adulthood (after P60), males with different developmental feeding history showed significant differences in multiple metrics of cognitive flexibility in learning and decision-making. Adult females with different developmental feeding history showed no differences in cognitive flexibility but did show significant differences in adult weight. We next applied reinforcement learning models to these behavioral data. The best fit models suggested that in males, developmental feeding history altered how mice updated their behavior after negative outcomes. This effect was sensitive to task context and reward contingencies. Consistent with these results, in males, we found that the two feeding history groups showed significant differences in the AMPAR/NMDAR ratio of excitatory synapses on nucleus-accumbens-projecting midbrain dopamine neurons and evoked dopamine release in dorsal striatal targets. Together, these data show in a rodent model that transient differences in feeding history in the juvenile-adolescent period can have significant impacts on adult weight, learning, decision-making, and dopamine neurobiology.

Anaesthesia induced with remimazolam and a fentanyl-series opioid can be reversed with flumazenil and naloxone. Concomitant paralysis with rocuronium can facilitate tracheal intubation whilst being reversible with sugammadex. Together, this combination might offer full reversibility of a 'routine' or a 'rapid-sequence' induction anaesthesia. Whether this is useful, or even safe, requires careful evaluation. [ABSTRACT FROM AUTHOR]

ABSTRACTBackground & objective Sugammadex is a drug used to reverse the muscle relaxation effect of rocuronium. Its use is still limited in preterm neonates. The aim of this study was to compare the efficacy of Sugammadex with that of neostigmine in reversing rocuronium-induced muscle relaxation in preterm neonates and to evaluate the safety of its use in this age group.Patients and methods This randomized clinical trial was carried out on Sixty preterm neonates, planned for elective inguinal hernia repair under general anaesthesia. The patients were divided into two equal groups. Group N used neostigmine and group S used Sugammadex as the reversal agent for rocuronium.Results In Sugammadex group the mean reversal time (1.15 ± 0.42) min and the mean recovery time (17 ± 6.64) min were significantly shorter than in the neostigmine group (8.9 ± 1.6) min and (27.16 ± 9.26) min respectively, with p value