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In this work, an analytical hybrid model, which consists of an analytical electromagnetic model and a global model, is developed to investigate the E to H mode transition in a planer inductively coupled plasma. By employing the hybrid model, the effect of discharge frequency, oxygen content, and gas pressure on the E to H mode transition is investigated. The results show that the electron density increases rapidly with coil current when the discharge shifts to the H mode, and the mode transition becomes smoother and occurs at lower current when the driving frequency is higher. As oxygen content increases, the electron density declines, and the threshold current for the mode transition exhibits a rising trend. The evolution of the threshold current with pressure is nonlinear; i.e., it decreases first and then increases, and the minimum value varies with discharge frequency. In addition, the plasma composition also changes during the E to H mode transition; i.e., all the charged species densities increase with coil current, except the O − density, which varies nonlinearly, and this indicates the decreasing electronegativity in the H mode. The results obtained in this work are helpful for understanding the effect of different dischar Ar / O 2 ge parameters on the E to H mode transition in Ar / O 2 inductive discharges. [ABSTRACT FROM AUTHOR]

Integrating multiple switching behaviors in a single material is conducive to the development of smart devices, but still faces challenges, especially in finding new types of multiresponsive materials. Hybrid metal halides have been becoming promising candidates with the potential to exhibit changes in various physical and chemical properties upon structural phase transitions. Herein, a pair of enantiomers (R/S‐3‐OHPD)PbI3 (1R/1S; 3‐HOPD = 3‐hydroxypiperidine cation) is reported to show multichannel switching behaviors around room temperature triggered by a combined order‐disorder and displacive type phase transition that arouses a large lattice reorganization and shape change of the crystals. Owing to the inherent chiral, noncentrosymmetric, and semiconducting characteristics of the compounds, five other switching behaviors are realized besides the macroscopic deformation, that is, enthalpy, dielectric permittivity, photoluminescence, circularly polarized light excited photoluminescence, and photoelectric response. This study provides an exciting example of phase transition crystals for the development of integrated multifunctional materials. [ABSTRACT FROM AUTHOR]

Lipoprotein(a) (Lp[a]) is associated with an increased risk of myocardial infarction (MI). However, the mechanism underlying this association has yet to be fully elucidated. This multicenter study aimed to investigate whether association between Lp(a) and MI risk is reinforced by the presence of low-attenuation plaque (LAP) identified by coronary computed tomography angiography (CCTA). In a derivation cohort, a total of 5,607 patients with stable chest pain suspected of coronary artery disease who underwent CCTA and Lp(a) measurement were prospectively enrolled. In validation cohort, 1,122 patients were retrospectively collected during the same period. High Lp(a) was defined as Lp(a) ≥50 mg/dL. The primary endpoint was a composite of time to fatal or nonfatal MI. Associations were estimated using multivariable Cox proportional hazard models. During a median follow-up of 8.2 years (Q1-Q3: 7.2-9.3 years), the elevated Lp(a) levels were associated with MI risk (adjusted HR [aHR]: 1.91; 95% CI: 1.46-2.49; P < 0.001). There was a significant interaction between Lp(a) and LAP (P interaction <0.001) in relation to MI risk. When stratified by the presence or absence of LAP, Lp(a) was associated with MI in patients with LAP (aHR: 3.03; 95% CI: 1.92-4.76; P < 0.001). Mediation analysis revealed that LAP mediated 73.3% (P < 0.001) for the relationship between Lp(a) and MI. The principal findings remained unchanged in the validation cohort. Elevated Lp(a) augmented the risk of MI during 8 years of follow-up, especially in patients with LAP identified by CCTA. The presence of LAP could reinforce the relationship between Lp(a) and future MI occurrence. [Display omitted] [ABSTRACT FROM AUTHOR]

Background and Objective: Vosoritide is a recently approved therapy for achondroplasia, the most common form of disproportionate short stature, that has been shown to be well tolerated and effective in increasing linear growth. This study aimed to develop a population pharmacokinetic (PPK) model to characterize pharmacokinetics (PK) of vosoritide and establish a weight-band dosing regimen. Methods: A PPK model was developed using data from five clinical trials in children with achondroplasia (aged 0.95−15 years) who received daily per-kg doses of vosoritide. The model was used to simulate expected exposures in children with a refined weight-band dosing regimen. Simulated exposure was compared with the observed exposure from the pivotal clinical trial to evaluate appropriateness of the weight-band dosing regimen. Results: A one-compartment model with a change-point first-order absorption and first-order elimination accurately described PK of vosoritide in children with achondroplasia. Body weight was found to be a predictor of vosoritide's clearance and volume of distribution. Additionally, it was observed that dosing solution concentration and duration of treatment influenced bioavailability. The weight-band dosing regimen resulted in simulated exposures that were within the range demonstrated to be well tolerated and effective in the pivotal clinical trial and showed improved consistency in drug exposure across the achondroplasia population. Conclusions: The weight-band dosing regimen reduced the number of recommended dose levels by body weight and is expected to simplify dosing for children with achondroplasia and their caregivers. Clinical Trial Registration: NCT02055157, NCT02724228, NCT03197766, NCT03424018, and NCT03583697. [ABSTRACT FROM AUTHOR]

Background and aims: ChatGPT is a powerful artificial intelligence (AI) chatbot developed by the OpenAI research laboratory which is capable of analysing human input and generating human‐like responses. Early research into the potential application of ChatGPT in healthcare has focused mainly on clinical and administrative functions. The diagnostic ability and utility of ChatGPT in histopathology is not well defined. We benchmarked the performance of ChatGPT against pathologists in diagnostic histopathology, and evaluated the collaborative potential between pathologists and ChatGPT to deliver more accurate diagnoses. Methods and results: In Part 1 of the study, pathologists and ChatGPT were subjected to a series of questions encompassing common diagnostic conundrums in histopathology. For Part 2, pathologists reviewed a series of challenging virtual slides and provided their diagnoses before and after consultation with ChatGPT. We found that ChatGPT performed worse than pathologists in reaching the correct diagnosis. Consultation with ChatGPT provided limited help and information generated from ChatGPT is dependent on the prompts provided by the pathologists and is not always correct. Finally, we surveyed pathologists who rated the diagnostic accuracy of ChatGPT poorly, but found it useful as an advanced search engine. Conclusions: The use of ChatGPT4 as a diagnostic tool in histopathology is limited by its inherent shortcomings. Judicious evaluation of the information and histopathology diagnosis generated from ChatGPT4 is essential and cannot replace the acuity and judgement of a pathologist. However, future advances in generative AI may expand its role in the field of histopathology. [ABSTRACT FROM AUTHOR]

Let { A n } n = 1 ∞ be a sequence of expanding matrices with A n ∈ M 2 ⁢ (ℤ) , and let { D n } n = 1 ∞ be a sequence of three-element digit sets with { x ∈ (0 , 1) 2 : ∑ d ∈ D n e 2 ⁢ π ⁢ i ⁢ 〈 d , x 〉 = 0 } = { ± 1 3 ⁢ (1 , i) t } , i ∈ { 1 , 2 } . The associated Moran measure generated by the infinite convolution μ { A n } , { D n } = δ A 1 - 1 ⁢ D 1 * δ A 1 - 1 ⁢ A 2 - 1 ⁢ D 2 * δ A 1 - 1 ⁢ A 2 - 1 ⁢ A 3 - 1 ⁢ D 3 * ⋯. In this paper, we give some necessary and sufficient conditions for μ { A n } , { D n } to be a spectral measure under some suitable conditions on A n and D n . [ABSTRACT FROM AUTHOR]

Proton pump inhibitors (PPIs) can affect the release of drugs from their dosage forms in vivo by elevating the gastric pH. Our recent clinical study has demonstrated that drug–drug interactions (DDIs) exist between a PPI, omeprazole, and nifedipine extended‐release formulations, where systemic exposure of nifedipine was increased in subjects after multiple‐dose pretreatment of omeprazole. However, the mechanism of the observed DDIs between omeprazole and nifedipine has not been well‐understood, as the DDI may also be mediated through CYP3A4 enzyme inhibition in addition to the elevated gastric pH caused by omeprazole. This study used physiologically‐based pharmacokinetic (PBPK) modeling and simulations to investigate the underlying mechanism of these complex DDIs. A formulation exhibiting differences in in vitro dissolution across physiological pH range and another formulation where pH does not impact dissolution appreciably (e.g., an osmotic pump) were chosen to characterize the potential impact of pH. The PBPK models incorporated two‐stage in vitro release profiles via US Pharmacopeia 2 apparatus. PBPK simulations suggest that the elevated gastric pH following multiple‐dose administration of omeprazole has a minimal effect on nifedipine pharmacokinetics (PKs), whereas CYP3A4‐mediated DDI is likely the main driver to the observed change of nifedipine PKs in the presence of omeprazole. Compared to the osmotic formulation, the slightly increased exposure of nifedipine can be accounted for by the enhanced drug release in the pH‐dependent formulation. The reported model‐based approach may be useful in DDI risk assessments, product formulation designs, and bioequivalence evaluations. [ABSTRACT FROM AUTHOR]

We investigate the uniqueness problems of meromorphic functions and their difference operators by using a new method. It is proved that if a non-constant meromorphic function f shares a non-zero constant and ∞ counting multiplicities with its difference operators Δcf(z) and Δ c 2 f (z) , then Δ c f (z) ≡ Δ c 2 f (z) . In particular, we give a difference analogue of a result of Jank–Mues–Volkmann. Our method has two distinct features: (i) It converts the relations between functions into the corresponding vectors. This makes it possible to deal with the uniqueness problem by linear algebra and combinatorics. (ii) It circumvents the obstacle of the difference logarithmic derivative lemma for meromorphic functions of infinite order, since this method does not depend on the growth of the functions. Furthermore, the idea in this paper can also be applied to the case for several variables. [ABSTRACT FROM AUTHOR]

The article examines the medical injury law and compensation systems in Taiwan. Topics discussed include civil and criminal medical malpractice law, procedures and trends in medical malpractice litigation, aspects of medical compensation systems, economics of Taiwan's medical injury compensation system, criminal law and physician's pursuit of criminal medical liability reform, amendment of Article 82 of the Medical Care Act and its intended and actual impact.

The effects of gas pressure and gas component on the power transfer efficiency η and transition power threshold P th during the E–H mode transition in inductively coupled plasmas are studied. The evolutions of η during the E–H mode transition in pure Ar and Ar/O2 discharges are similar, i.e., in E-mode discharge, η slightly increases with raising the applied power (η is below 30%), whereas, an abruptly upward jump of nearly two to four times for η occurs when the discharge transits to H-mode, and then η monotonously increases with increasing the applied power. In addition, as the pressure rises, η increases rapidly first and then slowly in pure Ar discharge. However, η in Ar/O2 mixture gases discharge shows a non-monotonic behavior. It reveals a tendency of first increase at low pressures and then decreases at high pressures, which is because the resistive component of the plasma varies with the electron density n e and the electron effective collision frequency ν eff . Furthermore, a non-monotonic behavior of transition power threshold P th with the pressure is found, i.e., with increasing the pressure, P th first decreases and then increases. It may be caused by the threshold electron density, which is constant at low pressures (ν eff / ω < 1) but increases at high pressures (ν eff / ω > 1). [ABSTRACT FROM AUTHOR]

Pharmacometric models were used to investigate the utility of biomarkers in predicting the efficacy (Crohn's Disease Activity Index [CDAI]) of brazikumab and provide a data‐driven framework for precision therapy for Crohn's disease (CD). In a phase IIa trial in patients with moderate to severe CD, treatment with brazikumab, an anti‐interleukin 23 monoclonal antibody, was associated with clinical improvement. Brazikumab treatment effect was determined to be dependent on the baseline IL‐22 (BIL22) or baseline C‐reactive protein (BCRP; predictive biomarkers), and placebo effect was found to be correlated with the baseline CDAI (a prognostic biomarker). A maximal total inhibition on CDAI input function of 50.6% and 42.4% was predicted for patients with extremely high BIL22 or BCRP, compared to a maximal total inhibition of 20.9% and 17.8% for patients with extremely low BIL22 or BCRP, respectively, which were mainly due to the placebo effect. We demonstrated that model‐derived baseline biomarker levels that achieve 50% of maximum unbound systemic concentration of 22.8 pg/mL and 8.03 mg/L for BIL22 and BCRP as the cutoffs to select subpopulations can effectively identify high‐response subgroup patients with improved separation of responders when compared to using the median values as the cutoff. This work exemplifies the utility of pharmacometrics to quantify biomarker‐driven responses in biologic therapies and distinguish between predictive and prognostic biomarkers, complementing clinical efforts of identifying subpopulations with higher likelihood of response to brazikumab. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance: Psoralea corylifolia Linn. (BGZ) is a commonly used traditional Chinese medicine (TCM) for the treatment of kidney-yang deficiency syndrome (Yangsyn) with good curative effect and security. However, BGZ was also reported to induce liver injury in recent years. According to TCM theory, taking BGZ may induce a series of adverse reactions in patients with kidney-yin deficiency syndrome (Yinsyn), which suggests that BGZ-induced liver damage may be related to its unreasonable clinical use. Aim of the study: Liver injury caused by TCM is a rare but potentially serious adverse drug reaction, and the identification of predisposed individuals for drug-induced liver injury (DILI) remains challenging. The study aimed to investigate the differential responses to BGZ in Yangsyn and Yinsyn rat models and identify the corresponding characteristic biomarkers. Materials and methods: The corresponding animal models of Yangsyn and Yinsyn were induced by hydrocortisone and thyroxine + reserpine respectively. Body weight, organ index, serum biochemistry, and Hematoxylin and Eosin (HE) staining were used to evaluate the liver toxicity effect of BGZ on rats with Yangsyn and Yinsyn. Transcriptomics and metabonomics were used to screen the representative biomarkers (including metabolites and differentially expressed genes (DEGs)) changed by BGZ in Yangsyn and Yinsyn rats, respectively. Results: The level changes of liver organ index, alanine aminotransferase (ALT), and aspartate aminotransferase (AST), suggested that BGZ has liver-protective and liver-damaging effects on Yangsyn and Yinsyn rats, respectively, and the results also were confirmed by the pathological changes of liver tissue. The results showed that 102 DEGs and 27 metabolites were significantly regulated related to BGZ's protective effect on Yangsyn, which is mainly associated with the glycerophospholipid metabolism, arachidonic acid metabolism, pantothenate, and coenzyme A (CoA) biosynthesis pathways. While 28 DEGs and 31 metabolites, related to the pathway of pantothenate and CoA biosynthesis, were significantly regulated for the BGZ-induced liver injury in Yinsyn. Furthermore, 4 DEGs (aldehyde dehydrogenase 1 family member B1 (Aldh1b1), solute carrier family 25 member 25 (Slc25a25), Pim-3 proto-oncogene, serine/threonine kinase (Pim3), out at first homolog (Oaf)) and 4 metabolites (phosphatidate, phosphatidylcholine, N-Acetylleucine, biliverdin) in the Yangsyn group and 1 DEG [galectin 5 (Lgals5)] and 1 metabolite (5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate) in Yinsyn group were significantly correlated to the ALT and AST levels of BGZ treated and untreated groups (receiver operating characteristic (ROC) ≥ 0.9). Conclusions: Yinsyn and Yangsyn are the predisposed syndromes for BGZ to exert liver damage and liver protection respectively, which are mainly related to the regulation of amino acid metabolism, lipid metabolism, energy metabolism, and metabolism of cofactors and vitamins. The results further suggest that attention should be paid to the selection of predisposed populations when using drugs related to the regulation of energy metabolism, and the Yinsyn/Yangsyn animal models based on the theory of TCM syndromes may be a feasible method for identifying the susceptible population to receive TCM. [ABSTRACT FROM AUTHOR]

For an expansive real matrix M=ρ−1C0ρ−1$M= \def\eqcellsep{&}\begin{bmatrix} \rho ^{-1} & \mathcal {C}\\ 0& \rho ^{-1} \end{bmatrix}$ and a noncollinear integer digit set D={(0,0)t,(α1,α2)t,(β1,β2)t}$D=\lbrace (0,0)^t,(\alpha _1,\alpha _2)^t,(\beta _1,\beta _2)^t\rbrace$ with α2−2β2∉3Z$\alpha _2-2\beta _2\notin 3\mathbb {Z}$, let μM,D$\mu _{M,D}$ be the self‐affine measure defined by μM,D(·)=13∑d∈DμM,D(M(·)−d)$\mu _{M,D}(\cdot)=\frac{1}{3}\sum _{d\in D}\mu _{M,D}(M(\cdot)-d)$. In this paper, some necessary and sufficient conditions for L2(μM,D)$L^2(\mu _{M,D})$ contains an infinite orthogonal exponential set or μM,D$\mu _{M,D}$ to be a spectral measure are given. [ABSTRACT FROM AUTHOR]

Frequent threats from landslides in reservoir areas have caused a research boom in academia due to the commissioning of the Three Gorges Project and the continued promotion of hydropower development in southwestern China. In this study, a series of analyses, mainly flume experiment, were conducted on reservoir slope deposits with large landslide potentials. This article focuses on validating the deformation and hydrological response process of the experimental re-enactment under different changing water level conditions and comparing them to real case observations and monitoring. The experimental results provide a basis for the systematic formulation of the mechanism of slope deposit failure in the reservoir area. The occurrence of landslides on slope deposits is usually caused by the accumulation of multiple phases of deformation rather than one phase of deformation. The deformation of the slope deposits is mainly in the form of erosion collapse at the front edge and shearing-tension cracking at the rear edge. These are directly caused by the large increase in the water level during the impoundment period and the rapid drawdown of the water level or the coupling of continuous strong rainfall and water level drawdown during the operation period. In this case, the loss of fine particles, the seepage force, and the increase in pore water pressure all play an important role. In this study, we hope to provide some scientific insights into the warning and mitigation of slope mounding hazards in reservoir areas. [ABSTRACT FROM AUTHOR]

A general approach to prepare superhydrophobic MOFs (denoted as MOFs-CF3) through a post-decorating strategy for highly efficient chemical fixation of CO2 was demonstrated. The enhanced catalytic activity of MOFs-CF3 is attributed to a synergistic effect between the Lewis acid sites of MOFs and modification of the electron-withdrawing trifluoromethyl group, which resulted in a high CO2 enrichment capacity. The possible mechanism of cycloaddition catalyzed by the MOFs-CF3 catalyst was also proposed. [ABSTRACT FROM AUTHOR]

This article discusses the potential benefits of virtual yoga as a non-pharmacological treatment for irritable bowel syndrome (IBS). IBS is a gastrointestinal disorder characterized by chronic abdominal pain and changes in bowel habits. The heterogeneity of IBS makes it challenging to treat, leading many patients to seek alternative therapies. Yoga, a mind-body practice originating from East Indian philosophy, has been shown to be safe and effective in reducing bowel symptoms and improving quality of life for IBS patients. A recent study examined the experiences of participants in a virtual yoga program and found that they reported increased awareness of their bodies and improved symptom management. The study also highlighted the importance of factors such as convenience, tailored treatment, autonomy, and social support in a successful digital behavioral therapeutic program. While virtual yoga shows promise as an alternative to in-person classes, further research is needed to fully understand its efficacy and potential limitations. [Extracted from the article]

Incorporating Fe-porphyrin into metal–organic framework furnished with fatty acids achieves selective CH 4 -to-CH 3 OH conversion. Akin to the microenvironment modulation in natural enzymes, the anchored hydrophobic fatty acids effectively tune CH 3 OH selectivity by perturbing the electronic state of Fe active sites, improving CH 4 adsorption, and restricting H 2 O 2 concentration around Fe sites, affording a remarkable CH 3 OH selectivity up to 77.0% in liquid products. [Display omitted] Inspiration from natural enzymes enabling creationary catalyst design is appealing yet remains extremely challenging for selective methane (CH 4) oxidation. This study presents the construction of a biomimetic catalyst platform for CH 4 oxidation, which is constructed by incorporating Fe-porphyrin into a robust metal – organic framework, UiO-66, furnished with saturated monocarboxylic fatty acid bearing different long alkyl chains. The catalysts demonstrate the high efficiency in the CH 4 to methanol (CH 3 OH) conversion at 50 °C. Moreover, the selectivity to CH 3 OH can be effectively regulated and promoted through a fine-tuned microenvironment by hydrophobic modification around the Fe-porphyrin. The long-chain fatty acids anchored on the Zr-oxo cluster of UiO-66 can not only tune the electronic state of the Fe sites to improve CH 4 adsorption, but also restrict the amount of H 2 O 2 around the Fe sites to reduce the overoxidation. This behavior resembles the microenvironment regulation in methane monooxygenase, resulting in high CH 3 OH selectivity. [ABSTRACT FROM AUTHOR]

In the etching process, a bias source is usually applied to the bottom electrode in inductively coupled plasmas (ICPs) to achieve independent control of the ion flux and ion energy. In this work, a hybrid model, which consists of a global model combined bi-directionally with a fluid sheath model, is employed to investigate the dual-frequency (DF) bias effect on the inductively coupled Cl2 plasmas under different pressures. The results indicate that the DC self-bias voltage developed on the biased electrode is approximately a linear function of the phase shift between the fundamental frequency and its second harmonic, and the value only varies slightly with pressure. Therefore, the ion energy on the bottom electrode can be modulated efficiently by the bias voltage waveform, i.e. the fluctuation of the ion energy with phase shift is about 40% for all pressures investigated. Besides, the ion energy and angular distribution functions (IEADFs) in DF biased inductive discharges is complicated, i.e. the IEADFs exhibits a four-peak structure under certain phase shift values. Although the species densities and ion fluxes also evolve with phase shift, the fluctuations are less obvious, especially for Cl2+ ions at low pressure. In conclusion, the independent control of the ion energy and ion flux are realized in DF biased ICPs, and the results obtained in this work are of significant importance for improving the etching process. [ABSTRACT FROM AUTHOR]

Objective: To discuss the clinical curative effect of heart-nourishing and spleen-fortifying decoction combined with consciousness-restoring and mind-regulating acupuncture method on moderate to severe depression after stroke. Methods: A total of 80 patients with post-stroke depression were divided into two groups as the control group and the study group according to a random number table method, with 40 cases in each group. There were 3 cases shedding off in the control group. Remaining 37 patients in the control group were treated with routine treatment. There were 2 cases shedding off in the study group. Remaining 38 patients in the study group were treated with heart-nourishing and spleen-fortifying decoction combined with consciousness-restoring and mind-regulating acupuncture method on the basis of the control group. The clinical effect after 6 weeks of treatment was compared between the two groups. The neurological function of the patients in the two groups was assessed by using the national institute of health stroke scale (NIHSS) before and after treatment. The modified Barthel index (MBI) was used to assess the self-care ability of the patients in the two groups before and after treatment. Levels of serum noradrenaline (NE), brainderived neurotrophic factor (BDNF), 5-hydroxytryptamine (5-HT) of the patients in the two groups were detected before and after treatment. Levels of the cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) of the patients in the two groups were measured before and after treatment. Results: The total effective rate of the study group after 6 weeks of treatment was obviously higher than that of the control group, and the difference was statistically significant (P < 0.05). After treatment, scores of NIHSS in the two groups were lower than those before treatment, and the difference was statistically significant (P < 0.05). After treatment, scores of MBI in the two groups were higher than those before treatment, and the difference was statistically significant (P < 0.05). After treatment, score of NIHSS in the study group was lower than that in the control group, and the difference was statistically significant (P < 0.05). After treatment, score of MBI in the study group was higher than that in the control group, and the difference was statistically significant (P < 0.05). After treatment, levels of NE, BDNF and 5-HT in the study group were higher than those before treatment and obviously higher than those in the control group, and the differences were statistically significant (P < 0.05). After treatment, level of MTT in the study group was lower than that before treatment and levels of CBF and CBV in the study group were higher than those before treatment, and the differences were statistically significant (P < 0.05). After treatment, level of MTT in the study group was lower than that in the control group and levels of CBF and CBV in the study group were higher than those in the control group, and the differences were statistically significant (P < 0.05). Conclusions: The heart-nourishing and spleen-fortifying decoction combined with consciousness-restoring and mind-regulating acupuncture method is helpful to improve the curative effect of post-stroke depression. Moreover, the therapy is beneficial to improve nerve function and self-care ability, increase cerebral blood perfusion level, and regulate the secretion of neurotransmitters. [ABSTRACT FROM AUTHOR]

Let μ M , D be the self-affine measure generated by an expansive matrix M ∈ M n (Z) and a finite digit set D ⊂ Z n . If { x ∈ (0 , 1) n : ∑ d ∈ D e 2 π i ⟨ d , x ⟩ = 0 } = q - 1 Z n ∩ (0 , 1) n for an integer q ≥ 2 , we show that μ M , D is a spectral measure if and only if M ∈ M n (q Z) and # D = q n . As an application, we settle down the spectral eigenmatrix problem of the spectral self-affine measure μ M , D . [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance: Psoralea corylifolia Linn. (BGZ) is a commonly used traditional Chinese medicine (TCM) for the treatment of kidney-yang deficiency syndrome (Yangsyn) with good curative effect and security. However, BGZ was also reported to induce liver injury in recent years. According to TCM theory, taking BGZ may induce a series of adverse reactions in patients with kidney-yin deficiency syndrome (Yinsyn), which suggests that BGZ-induced liver damage may be related to its unreasonable clinical use. Aim of the study: Liver injury caused by TCM is a rare but potentially serious adverse drug reaction, and the identification of predisposed individuals for drug-induced liver injury (DILI) remains challenging. The study aimed to investigate the differential responses to BGZ in Yangsyn and Yinsyn rat models and identify the corresponding characteristic biomarkers. Materials and methods: The corresponding animal models of Yangsyn and Yinsyn were induced by hydrocortisone and thyroxine + reserpine respectively. Body weight, organ index, serum biochemistry, and Hematoxylin and Eosin (HE) staining were used to evaluate the liver toxicity effect of BGZ on rats with Yangsyn and Yinsyn. Transcriptomics and metabonomics were used to screen the representative biomarkers (including metabolites and differentially expressed genes (DEGs)) changed by BGZ in Yangsyn and Yinsyn rats, respectively. Results: The level changes of liver organ index, alanine aminotransferase (ALT), and aspartate aminotransferase (AST), suggested that BGZ has liver-protective and liver-damaging effects on Yangsyn and Yinsyn rats, respectively, and the results also were confirmed by the pathological changes of liver tissue. The results showed that 102 DEGs and 27 metabolites were significantly regulated related to BGZ's protective effect on Yangsyn, which is mainly associated with the glycerophospholipid metabolism, arachidonic acid metabolism, pantothenate, and coenzyme A (CoA) biosynthesis pathways. While 28 DEGs and 31 metabolites, related to the pathway of pantothenate and CoA biosynthesis, were significantly regulated for the BGZ-induced liver injury in Yinsyn. Furthermore, 4 DEGs (aldehyde dehydrogenase 1 family member B1 (Aldh1b1), solute carrier family 25 member 25 (Slc25a25), Pim-3 proto-oncogene, serine/threonine kinase (Pim3), out at first homolog (Oaf)) and 4 metabolites (phosphatidate, phosphatidylcholine, N-Acetylleucine, biliverdin) in the Yangsyn group and 1 DEG [galectin 5 (Lgals5)] and 1 metabolite (5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate) in Yinsyn group were significantly correlated to the ALT and AST levels of BGZ treated and untreated groups (receiver operating characteristic (ROC) ≥ 0.9). Conclusions: Yinsyn and Yangsyn are the predisposed syndromes for BGZ to exert liver damage and liver protection respectively, which are mainly related to the regulation of amino acid metabolism, lipid metabolism, energy metabolism, and metabolism of cofactors and vitamins. The results further suggest that attention should be paid to the selection of predisposed populations when using drugs related to the regulation of energy metabolism, and the Yinsyn/Yangsyn animal models based on the theory of TCM syndromes may be a feasible method for identifying the susceptible population to receive TCM. [ABSTRACT FROM AUTHOR]

Introduction: As a key determinant of cardiovascular performance, vascular-arterial coupling (VAC) has been reported to be a predictor of clinical outcomes in various clinical scenarios. However, few studies have explored how acute fluid removal during hemodialysis (HD) impacts the interaction between cardiac function and the arterial system. Methods: We recruited 317 HD patients from an established renal dialysis unit for this cross-sectional study and a total of 285 were included in the final analyses. We measured left ventricle end-systolic elastance (Ees), the effective arterial elastance (Ea), and VAC before and after HD using noninvasive echocardiographic measurements. We also compared echocardiographic and hemodynamic parameters in ventriculo-arterial coupling and ventriculo-arterial uncoupling patients. Results: HD significantly altered partial ventricular and vascular function parameters such as blood pressure, left ventricular end-diastolic volume, stroke volume, left ventricular ejection fraction, and systemic vascular resistance index. Ea increased following HD from 3.5 ± 1.4 to 4.2 ± 1.8 mm Hg/mL (p < 0.0001), Ees increased following HD from 7.9 ± 5.5 to 9.2 ± 6.9 mm Hg/mL (p = 0.04), whereas VAC did not markedly alter as a result of HD. Ventriculo-arterial uncoupling was found to be related to abnormal cardiac structure and worse systolic function. Conclusions: VAC obtained from echocardiography is likely to be load-independent and useful as a reliable index for stratifying the risk of cardiovascular diseases in HD patients. Further investigations on larger patient cohorts are needed to further validate our findings. [ABSTRACT FROM AUTHOR]

Background: Lymphoepithelioma-like intrahepatic cholangiocarcinoma (LEICC) has been recently introduced as a genetically distinct of intrahepatic cholangiocarcinoma (ICC). We aimed to investigate whether LEICC has distinct radiological characteristics in comparison with classical ICC, and to determine MRI features that can be used to differentiate LEICC from classical ICC. Methods: Five hundred and sixty-seven consecutive patients who underwent surgical resection or liver transplantation for ICC between 2014 and 2021 were retrospectively identified. Among them, 30 patients with LEICC (LEICC-cohort) and 116 with stage-matched classical ICC (control-cohort) were finally included. Pre-operative MRI data were compared between the two cohorts. Multivariable logistic regression analysis was performed to determine relevant imaging features suggesting the diagnosis of LEICC over classical ICC. Results: LEICCs showed significantly higher frequencies of a non-rim arterial phase hyperenhancement (APHE), washout on post-arterial images and a smooth margin, as well as less frequencies of perilesional enhancement and liver capsular retraction when compared with classical ICCs (P < 0.05 for all). The multivariate analysis revealed that non-rim APHE (odds ratio, 10.863; 95% CI [3.295–35.821]; P < 0.001) and the absence of perilesional enhancement (odds ratio, 3.350; 95% CI [1.167–9.619]; P = 0.025) are significant independent imaging features that suggest the diagnosis of LEICCs over classical ICCs. Conclusions: Compared with classical ICCs, LEICCs do have distinct radiological characteristics. A smooth margin, non-rim APHE, washout on post-arterial images, absent perilesional enhancement and absent liver capsular retraction are useful MRI features that could help to differentiate LEICCs from classical ICCs. [ABSTRACT FROM AUTHOR]

For approval, a proposed generic drug product must demonstrate it is bioequivalent (BE) to the reference listed drug product. For locally acting drug products, conventional BE approaches may not be feasible because measurements in local tissues at the sites of action are often impractical, unethical, or cost‐prohibitive. Mechanistic modeling approaches, such as physiologically‐based pharmacokinetic (PBPK) modeling, may integrate information from drug product properties and human physiology to predict drug concentrations in these local tissues. This may allow clinical relevance determination of critical drug product attributes for BE assessment during the development of generic drug products. In this regard, the Office of Generic Drugs of the US Food and Drug Administration has recently established scientific research programs to accelerate the development and assessment of generic products by utilizing model‐integrated alternative BE approaches. This report summarizes the presentations and panel discussion from a public workshop that provided research updates and information on the current state of the use of PBPK modeling approaches to support generic product development for ophthalmic, injectable, nasal, and implant drug products. [ABSTRACT FROM AUTHOR]

Epigenetic reprogramming plays a critical role in chondrocyte senescence during osteoarthritis (OA) pathology, but the underlying molecular mechanisms remain to be elucidated. Here, using large-scale individual datasets and genetically engineered (Col2a1-CreERT2; Eldr flox/flox and Col2a1-CreERT2; ROSA26 -LSL- Eldr +/+ knockin) mouse models, we show that a novel transcript of long noncoding RNA ELDR is essential for the development of chondrocyte senescence. ELDR is highly expressed in chondrocytes and cartilage tissues of OA. Mechanistically, exon 4 of ELDR physically mediates a complex consisting of hnRNPL and KAT6A to regulate histone modifications of the promoter region of IHH , thereby activating hedgehog signaling and promoting chondrocyte senescence. Therapeutically, GapmeR-mediated silencing of ELDR in the OA model substantially attenuates chondrocyte senescence and cartilage degradation. Clinically, ELDR knockdown in cartilage explants from OA-affected individuals decreased the expression of senescence markers and catabolic mediators. Taken together, these findings uncover an lncRNA-dependent epigenetic driver in chondrocyte senescence, highlighting that ELDR could be a promising therapeutic avenue for OA. [Display omitted] Ji and colleagues identify ELDR as a critical regulator of chondrocyte senescence. Mechanistically, the core region of ELDR physically mediates a complex consisting of hnRNPL and KAT6A to regulate histone modifications of the promoter region of IHH , thereby activating hedgehog signaling. [ABSTRACT FROM AUTHOR]

A bias power is usually applied in inductively coupled plasmas (ICP) to realize the separate control of the plasma density and the ion energy. In this research, a two-dimensional fluid/electron Monte Carlo hybrid model is developed to self-consistently investigate the bias effect on the stochastic heating and on the radial homogeneity in a biased argon ICP operated at low pressure (3 mTorr). The results show that the temporal evolution of the stochastic heating exhibits a plateau and a peak when the sheath collapses at high bias voltages, due to the limited sheath heating and the electron inertia. In addition, the plasma density in the diffusion chamber increases with bias voltage and bias frequency, because of the more pronounced stochastic heating both at the substrate and at the grounded wall. In the main discharge chamber, the plasma density decreases with bias voltage, due to the compression of the bulk plasma region, and this trend becomes less obvious at high bias frequency, because of the enhanced power absorption caused by the stochastic heating. Therefore, it is concluded that by tuning the bias voltage and bias frequency, the plasma radial uniformity could be modulated efficiently, which is very important for improving plasma processing. [ABSTRACT FROM AUTHOR]

Entrustable Professional Activities (EPAs) are defined as a process of gradually entrusting key tasks to specialty fellows during their training. EPAs are an important component of competency-based medical education; the concept of entrustment is also familiar and intuitive to clinical faculty, even inexperienced evaluators even if not termed as such. In this paper, we describe the process of how the authors adopted an established EPA framework for gastroenterology training, using EPAs to guide curriculum and faculty development and assessment in ten steps: (1) adopting an established framework, (2) mapping EPAs to relevant competencies, (3) specifying expected behaviors for competency of each EPA, (4) training faculty and fellows to have a shared mental model, (5) designing the training curriculum and educational strategies based on EPAs, (6) determining the assessment strategy, (7) designing the assessment tool, (8) ensuring clarity in how assessment data are used to make summative decisions, (9) changing feedback culture of fellows, and (10) using a longitudinal coaching system to improve EPA performance. [ABSTRACT FROM AUTHOR]

Objective: To investigate the characteristics and associations of MRI-visible perivascular spaces (PVS) with clinical progression and longitudinal cognitive decline across the Alzheimer's disease spectrum. Methods: We included 1429 participants (641 [44.86%] female) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. PVS number and grade in the centrum semiovale (CSO-PVS), basal ganglia (BG-PVS), and hippocampus (HP-PVS) were compared among the control (CN), mild cognitive impairment (MCI), and Alzheimer's disease (AD) groups. PVS were tested as predictors of diagnostic progression (i.e., CN to MCI/AD or MCI to AD) and longitudinal changes in the 13-item Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog 13), Mini-Mental State Examination (MMSE), memory (ADNI-MEM), and executive function (ADNI-EF) using multiple linear regression, linear mixed-effects, and Cox proportional hazards modeling. Results: Compared with CN subjects, MCI and AD subjects had more CSO-PVS, both in number (p < 0.001) and grade (p < 0.001). However, there was no significant difference in BG-PVS and HP-PVS across the AD spectrum (p > 0.05). Individuals with moderate and frequent/severe CSO-PVS had a higher diagnostic conversion risk than individuals with no/mild CSO-PVS (log-rank p < 0.001 for all) in the combined CN and MCI group. Further Cox regression analyses revealed that moderate and frequent/severe CSO-PVS were associated with a higher risk of diagnostic conversion (HR = 2.007, 95% CI = 1.382–2.914, p < 0.001; HR = 2.676, 95% CI = 1.830–3.911, p < 0.001, respectively). A higher CSO-PVS number was associated with baseline cognitive performance and longitudinal cognitive decline in all cognitive tests (p < 0.05 for all). Conclusions: CSO-PVS were more common in MCI and AD and were associated with cognitive decline across the AD spectrum. [ABSTRACT FROM AUTHOR]

The exposed facets of supported catalysts play a crucial role in catalysis; however, they are usually ignored and related studies remain rare. Herein, we have fabricated a series of sandwich‐structured metal–organic framework composites, denoted ZIF‐8X@Pd@ZIF‐8 (x represents the morphology of ZIF‐8 core, i.e. ZIF‐8C exposing (100) facet, ZIF‐8RD exposing (110) facet, and ZIF‐8TRD exposing mixed (100) and (110) facets), featuring Pd nanoparticles deposited on the specific crystal facets of ZIF‐8 core, for hydrogenation of p‐chloronitrobenzene. The Pd electronic state is tailored by the ZIF‐8 core, where more electron‐deficient Pd is found in ZIF‐8C@Pd@ZIF‐8 than that in ZIF‐8RD@Pd@ZIF‐8, leading to discriminative adsorption of the −NO2 and −Cl groups of p‐chloronitrobenzene. Consequently, ZIF‐8C@Pd@ZIF‐8 exhibits excellent activity (97.6 %) and selectivity (98.1 %) to p‐chloroaniline. This work highlights crystal facet engineering of supports to modulate the microenvironment and electronic state of supported metal nanoparticles, offering a promising avenue to enhanced catalysis. [ABSTRACT FROM AUTHOR]

The exposed facets of supported catalysts play a crucial role in catalysis; however, they are usually ignored and related studies remain rare. Herein, we have fabricated a series of sandwich‐structured metal–organic framework composites, denoted ZIF‐8X@Pd@ZIF‐8 (x represents the morphology of ZIF‐8 core, i.e. ZIF‐8C exposing (100) facet, ZIF‐8RD exposing (110) facet, and ZIF‐8TRD exposing mixed (100) and (110) facets), featuring Pd nanoparticles deposited on the specific crystal facets of ZIF‐8 core, for hydrogenation of p‐chloronitrobenzene. The Pd electronic state is tailored by the ZIF‐8 core, where more electron‐deficient Pd is found in ZIF‐8C@Pd@ZIF‐8 than that in ZIF‐8RD@Pd@ZIF‐8, leading to discriminative adsorption of the −NO2 and −Cl groups of p‐chloronitrobenzene. Consequently, ZIF‐8C@Pd@ZIF‐8 exhibits excellent activity (97.6 %) and selectivity (98.1 %) to p‐chloroaniline. This work highlights crystal facet engineering of supports to modulate the microenvironment and electronic state of supported metal nanoparticles, offering a promising avenue to enhanced catalysis. [ABSTRACT FROM AUTHOR]

It is known that fine granular area morphology is often formed around interior micro‐defect in the case of very high cycle fatigue failure of high strength steel. The mechanism of "fragmentation of martensitic laths and formation of dislocation cells" (Zhu's model), which revealed a microstructure‐dependent crack initiation and early growth for micro‐defect induced internal fatigue cracking, was discussed in several lathy martensitic or similar steels, verified under environmental fatigue, and applicable to white etching crack in rotating contact fatigue. A machine learning‐Z parameter integrated approach was developed for fatigue life, which is promising for design against fatigue of engineering structures for long life. Highlights: The FGA model of martensitic steels in air (Zhu's model) was illustrated.Zhu's model was confirmed in environmental media and similar steels.Zhu's model was applicable to white etching crack in rotating contact fatigue.Machine learning‐Z parameter was integrated for fatigue life prediction. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) human pose estimation aims to locate 3D keypoints of individuals from given input RGB images. For two-dimensional (2D) human pose estimation problems, majority methods inferring 2D poses are from 2D heatmaps. However, it is hard to extend this method to 3D poses inferring area which makes computational loads increase sharply. To address the above problem, we propose STM-CNN method to estimate reconstruction coefficient matrix to calculate the final 3D pose instead of estimating 3D heatmaps to decrease the computational loads. First, STM-CNN does a preprocessing procedure to calculate a set of shape and weight bases. Second, STM-CNN infers a 2D matrix called reconstruction coefficient from the STM-CNN architecture. Third, STM-CNN utilizes the preprocessing shape and weight bases and estimated reconstruction coefficient matrix to calculate the final 3D pose. Meanwhile, STM-CNN method achieves better performances compared with the state-of-the-art methods on Human3.6M. [ABSTRACT FROM AUTHOR]

Background: Lymph or chyle leak (LL/CL) is severe complications after lateral cervical lymph node dissection (LLND), mainly due to iatrogenic injury of the lymphatic duct. Efficient and well-operated methods to reduce postoperative drainage are still lacking. This was a feasibility study to evaluate a new method of preventing LL/CL compared to conventional treatment. Method: We retrospectively analyzed 20 consecutive patients who used the "pedicled omohyoid flap covering (POFC)" method during LLND from January 2019 to December 2021 in our center as an observation group. Another 20 consecutive patients used the conventional method during LLND in this period as a control group. The clinical and pathological features of the two groups were compared, and the related factors that affected postoperative lymphatic drainage were analyzed with Cox proportional hazards models. Results: The drainage volume per 24 h and the incidence of LL/CL in the control group were both higher than that in the observation group (all P < 0.05), and the number of lymph nodes dissected in the IV region > 10 and the use of the POFC method were the independent risk factors that significantly affected the incidence of LL/CL post LLND (all P < 0.05). Conclusions: POFC is a safe and useful method for reducing drainage and preventing LL/CL post-LLND, especially for patients with heavy metastasis of the lymph nodes in the IV region. [ABSTRACT FROM AUTHOR]

It has been demonstrated that polyoxometalates (POMs) have strong anchoring abilities with efficient catalysis of lithium polysulfides (LiPSs). However, the severe aggregation that buries the effective active sites of POMs along with poor electrical conductivity limits the practical application of POMs in lithium sulfur batteries (LSBs). In our strategy, we utilized reduced graphene oxide (rGO) to support a POM catalyst entrapped in a MIL-88A(FeCo) network with a hollow shell skeleton as the sulfur host material. H4PW11VO40 (PW11V) with optimal vanadium atom implantation ensures the ruggedness and integrity of the hollow structure, which is conducive to achieving high sulfur loading as well as accommodating the volume change of the sulfur cathode during the charging and discharging process. Importantly, PW11V can capture polysulfides through firm chemical adsorption and accelerate redox reactions of LiPS conversion by effective electrochemical catalysis. Furthermore, the satisfactory electrical conductivity of rGO provides access for electrons to reach the interface of PW11V and polysulfides and trigger Li–S conversion reactions. Thus, the constructed PW11V-based sulfur cathode exhibited a superior specific capacity of 905 mA h g−1 after 100 cycles under 0.2 C and long cycling life with a capacity recession rate of 0.046% for each cycle upon 500 cycles under 3 C. This research reveals the effect of vanadium atom substitution of POMs on the cycling performance of a sulfur cathode and affords insight for developing high-performance LSBs. [ABSTRACT FROM AUTHOR]

The effect of a reservoir on quantum communication depends on its spectral density. The efficiency of quantum teleportation and dense coding is explored when each one of the channel qubits is coupled simultaneously to multiple bosonic reservoirs. It is shown that the non-Markovianity triggered by increasing the reservoir number can induce revivals of quantum advantages of the two protocols after their disappearance. However, the backflow of information to the system that signifies non-Markovianity does not always induce immediate revivals of the quantum advantages. There may be a delayed effect for some initial states, and only as the backflow of information accumulates to a certain extent can the revivals of quantum advantages be triggered. [ABSTRACT FROM AUTHOR]

Background: A significant number of patients with mild traumatic brain injury (mTBI) would experience cognitive deficit. Purpose: To investigate the brain structural changes in sub-acute mTBI by diffusion kurtosis imaging (DKI) and volumetric analysis, and to assess the relationship between brain structural changes and cognitive functions. Material and Methods: A total of 23 patients with sub-acute mTBI and 24 control participants were recruited. All the participants underwent examinations of neuropsychological tests, DKI, and magnetic resonance imaging (MRI)-based morphological scans. Images were investigated using whole brain-based analysis and further regions of interest-based analysis for subcortical nuclei. The neuropsychological tests were compared between the mTBI and the control group. Correlation analysis was performed to examine the relationship between gray matter (GM) volume, DKI parameters, and cognitive functions. Results: Compared with control participants, mTBI patients performed worse in the domains of verbal memory, attention and executive function (P < 0.05). No regional GM volume differences were observed between the mTBI and control groups (P > 0.05). Using DKI, patients with mTBI showed lower mean kurtosis (MK) in widespread white matter (WM) regions and several subcortical nuclei (P < 0.05), and higher mean diffusivity (MD) in the right pallidum (P < 0.05). Lower MK value of multiple WM regions and several subcortical nuclei correlated with cognitive impairment (P < 0.05). Conclusion: DKI was sensitive in detecting brain microstructural changes in patients with sub-acute mTBI showing lower MK value in widespread WM regions and several subcortical nuclei, which were statistically associated with cognitive deficits. [ABSTRACT FROM AUTHOR]

We use a dual-network model to simulate heat and mass transfer in porous media. The model captures pore-scale information in meter-scale simulations and allows for non-equilibrium between the solid and pore space. We apply the model to predict the effective thermal diffusivity in networks representing Bentheimer sandstone, Estaillades limestone and two random packings of monodisperse spheres. Non-Fourier transport at early times can lead to both higher and lower thermal dispersivity than currently assumed using a volume-weighted average of fluid and solid properties. Furthermore, we quantify the mechanical dispersion coefficient caused by differences in local flow velocity, which further contributes to thermal dispersion of the plume. We discuss the results in the context of the design and management of ATES (aquifer thermal energy storage). Ignoring pore-scale velocity and temperature fluctuations in the estimation of averaged properties can lead to errors of more than 50%. The work provides a framework to predict thermal properties of porous media under different flow conditions for more accurate prediction and design of thermal energy storage. • A dual network model simulated heat and mass transfer with non-equilibrium between the solid and pore space. • Pore-scale fluctuations in temperature and velocity impact averaged thermal transport properties. • Predictions of thermal diffusivity and dispersion can aid the design of subsurface thermal storage. [ABSTRACT FROM AUTHOR]

[Display omitted] Tumor-associated macrophages (TAMs), one of the major immune cell types in colorectal cancer (CRC) tumor microenvironment (TME), play indispensable roles in immune responses against tumor progression. In this study, we aimed to know whether the extensive inter and intra heterogeneity of TAMs contributes to the clinical outcomes and indications for immune checkpoint blockade (ICB) in CRC. We used single-cell RNA sequencing (scRNA-Seq) data from 60 CRC patients and charactrized TAMs based on anatomic locations, tumor regions, stages, grades, metastatic status, MSS/MSI classification and pseudotemporal differentiation status. We then defined a catalog of 21 gene modules that determine macrophage status, and identified 7 of them as relevant to clinical outcomes and 11 as indications for ICB therapy. On this basis, we constructed a unique TAM subgroup profile, aiming to find features that may be highly responsive to immunotherapy for the CRC with poor prognosis under conventional treatment. This TAM subpopulation is enriched in tumors and is associated with poor prognosis, but exhibits a high immunotherapy response signature (HIM TAM). Further spatial transcriptome analysis and ligand-receptor interaction analysis confirmed that HIM TAM is involved in shaping TIME, especially the regulation of T cells. Our study provides insights into different TAM subtypes, highlights the importance of TAM heterogeneity in relation to patient prognosis and immunotherapy response, and reveals potential immunotherapy strategies based on TAM characteristics for CRC that does not respond well to conventional therapy. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a highly heterogeneous malignancy, and patients often have different responses to treatment. In this study, the genetic characteristics related to exosome formation and secretion procedure were used to predict chemoresistance and guide the individualized treatment of patients. Firstly, seven microarray datasets in Gene Expression Omnibus (GEO) and RNA-Seq dataset from the Cancer Genome Atlas (TCGA) were used to analysis the transcriptome profiles and associated characteristics of CRC patients. Then, a predictive model based on gene features linked to exosome formation and secretion was created and validated using Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) machine learning. Finally, we evaluated the model using chemoresistant/chemosensitive cells and tissues by immunofluorescence (IF), western blot (WB), quantitative real-time PCR (qRT-PCR) and immunocytochemistry (IHC) experiments, and the predictive value of integrated model in the clinical validation cohort were performed by Receiver Operating Characteristic (ROC) and Kaplan-Meier (K-M) curves analyses. We established a risk score signature based on three genes related to exosome secretion in CRC. Better Overall Survival (OS) and greater chemosensitivity were seen in the low-risk group, whereas the high-risk group exhibited chemoresistance and a subpar response to immune checkpoint blockade (ICB) therapy. Higher expression of the model genes EXOC2, EXOC3 and STX4 were observed in chemoresistant cells and specimens. The AUC of 5-year disease-free survival (DFS) was 0.804. Compared with that in the low-risk group, patients' DFS was found to be significantly worse in the high-risk group. In summary, the gene signature related to exosome formation and secretion could reliably predict patients' chemosensitivity and ICB treatment response, which providing new independent biomarkers for the treatment of CRC. [ABSTRACT FROM AUTHOR]

Highlights: The spatial distribution pattern, DSGSD characteristics and influence of the controlling factors of reservoir rock landslides were analyzed in Southwest China.The contribution of DSGSD to sliding deformation of a rock slope with landslide potential in the reservoir area was obtained.The mode of DSGSD evolution into landslides was summarized considering different combinations of bedding dip and slope angles.The spatial distribution pattern, DSGSD characteristics and influence of the controlling factors of reservoir rock landslides were analyzed in Southwest China.The contribution of DSGSD to sliding deformation of a rock slope with landslide potential in the reservoir area was obtained.The mode of DSGSD evolution into landslides was summarized considering different combinations of bedding dip and slope angles. [ABSTRACT FROM AUTHOR]

The teaching of endoscopic procedures to trainees has radically changed from the previous "see one, do one, teach one" approach to the method termed "competency-based medical education" (CBME), which has transformed endoscopic training. Successful implementation of a CBME program requires learners to direct their own learning. Learners with a growth approach are more likely to thrive in such a system since they are learning-oriented and not performance-oriented. This method dictates that endoscopy mentors take a longer-term and broader view of the development of the trainee and are vital to cultivate a growth mindset in learners, while an endoscopy coach focuses on helping trainees apply principles of mastery learning and deliberate practice. The goal of the authors was to describe some principles of effective coaching and mentoring methods as applied to endoscopy training. [ABSTRACT FROM AUTHOR]

Background and Objective: Vosoritide, an analog of C-type natriuretic peptide, has been developed for the treatment of children with achondroplasia. The pharmacokinetics of vosoritide and relationships between plasma exposure and efficacy, biomarkers, and safety endpoints were evaluated in a phase II, open-label, dose-escalation study (N = 35 patients aged 5–14 years who received daily subcutaneous injections for 24 months) and a phase III, double-blind, placebo-controlled study (N = 60 patients aged 5–18 years randomized to receive daily subcutaneous injections for 52 weeks). Methods: Pharmacokinetic parameters for both studies were obtained from non-compartmental analysis. Potential correlations between vosoritide exposure and changes in annualized growth velocity, collagen type X marker (CXM; a biomarker of endochondral ossification), cyclic guanosine monophosphate (cGMP; a biomarker of pharmacological activity), heart rate, and systolic and diastolic blood pressures were then evaluated. Results: The exposure–response relationships for changes in both annualized growth velocity and the CXM biomarker saturated at 15 μg/kg, while systemic pharmacological activity, as measured by urinary cGMP, was near maximal or saturated at exposures obtained at the highest dose studied (i.e. 30 μg/kg). This suggested that the additional bioactivity was likely in tissues not related to endochondral bone formation. In the phase III study, following subcutaneous administration at the recommended dose of 15 μg/kg to patients with achondroplasia aged 5–18 years, vosoritide was rapidly absorbed with a median time to maximal plasma concentration (Cmax) of 15 minutes, and cleared with a mean half-life of 27.9 minutes after 52 weeks of treatment. Vosoritide exposure (Cmax and area under the concentration-time curve [AUC]) was consistent across visits. No evidence of accumulation with once-daily dosing was observed. Total anti-vosoritide antibody (TAb) responses were detected in the serum of 25 of 60 (42%) treated patients in the phase III study, with no apparent impact of TAb development noted on annualized growth velocity or vosoritide exposure. Across the exposure range obtained with 15 µg/kg in the phase III study, no meaningful correlations between vosoritide plasma exposure and changes in annualized growth velocity or CXM, or changes from predose heart rate, and systolic or diastolic blood pressures were observed. Conclusions: The results support the recommended dose of vosoritide 15 µg/kg for once-daily subcutaneous administration in patients with achondroplasia aged ≥ 5 years whose epiphyses are not closed. Clinical Trials Registration: NCT02055157, NCT03197766, and NCT01603095. [ABSTRACT FROM AUTHOR]

The remote control of coherence is a crucial step for its application in quantum computation. The maximal steered coherence (MSC) and its conversion to entanglement in multiple bosonic reservoirs are investigated. It is shown that the MSC decays with time in the Markovian regime and behaves as damped oscillations in the non‐Markovian regime. The MSC can also be connected directly to the strength of non‐Markovianity, through which it is shown that it can be noticeably enhanced by taking full advantage of the non‐Markovian effects. Besides, the MSC can be converted completely to entanglement via optimal incoherent operation applied to the steered qubit and an incoherent ancilla which is immune to decoherence, and the generated entanglement is stronger than the shared entanglement in prior. These findings suggest a potential way for remotely generating and manipulating coherence and entanglement in noisy environments. [ABSTRACT FROM AUTHOR]

This paper documents the zircon U–Pb ages, whole-rock geochemistry, and Sr–Nd–Pb isotopes of the Mesozoic granites in the central part of the North Qilian Orogenic Belt to provide information on the tectonic evolution and crustal accretion process of the Qilian Orogenic Belt. Zircon U–Pb dating yields an age of 215.3 ± 3.1 Ma, indicating that the Beidaban monzogranites formed from Late Triassic. They are characterized by high contents of SiO2, Al2O3, and K2O; are slightly peraluminous (A/CNK = 1.08–1.15); and have mineralogical assemblages of primary biotite and ilmenite, illustrating that they are shoshonitic and peraluminous S-type granite. The Beidaban monzogranites have initial (87Sr/86Sr)i values ranging from 0.71456 to 0.71867 and εNd(t) values ranging from –12.9 to –8.5 with two-stage Nd model ages of 1.69–2.04 Ga, suggesting that they originated from partial melting of the Paleo-Mesoproterozoic (Longshoushan Group) continental crustal metasedimentary rocks. Initial Pb isotopic compositions (206Pb/204Pb = 19.44–21.80; 207Pb/204Pb = 15.76–15.89; 208Pb/204Pb = 39.62–41.26) and geochemical features such as high Th/Ta (9.3–67.4, 37.4 on average) and Rb/Nb (12.5–17.1) are consistent with recycled crustal components. Combined with previous geochronological and geochemical data, we suggest that the Mesozoic granites probably formed in a post-collisional tectonic setting and that the North Qilian Orogen Belt experienced comprehensive intracontinental orogenesis after the closure of the Qilian ocean. [ABSTRACT FROM AUTHOR]

The development of generic ophthalmic drug products with complex formulations is challenging due to the complexity of the ocular system and a lack of sensitive testing to evaluate the interplay of its physiology with ophthalmic drugs. New methods are needed to facilitate the development of ophthalmic generic drug products. Ocular physiologically based pharmacokinetic (O-PBPK) models can provide insight into drug partitioning in eye tissues that are usually not accessible and/or are challenging to sample in humans. This study aims to demonstrate the utility of an ocular PBPK model to predict human exposure following the administration of ophthalmic suspension. Besifloxacin (Bes) suspension is presented as a case study. The O-PBPK model for Bes ophthalmic suspension (Besivance® 0.6%) accounts for nasolacrimal drainage, suspended particle dissolution in the tears, ocular absorption, and distribution in the rabbit eye. A topical controlled release formulation was used to integrate the effect of Durasite® on Bes ocular retention. The model was subsequently used to predict Bes exposure after its topical administration in humans. Drug-specific parameters were used as validated for rabbits. The physiological parameters were adjusted to match human ocular physiology. Simulated human ocular pharmacokinetic profiles were compared with the observed ocular tissue concentration data to assess the OCAT models' ability to predict human ocular exposure. The O-PBPK model simulations adequately described the observed concentrations in the eye tissues following the topical administration of Bes suspension in rabbits. After adjustment of physiological parameters to represent the human eye, the extrapolation of clinical ocular exposure following a single ocular administration of Bes suspension was successful. [ABSTRACT FROM AUTHOR]

Camel milk (CM) is considered to protect the liver in the practice of traditional medicine in nomadic areas. The purpose of the present study was to investigate the effects of CM on the hepatic biochemical and multiple omics alterations induced by chronic alcoholic liver disease (ALD). An intragastric gavage mice Lieber DeCarli + Gao binge model (NIAAA model) was employed to investigate the inflammatory mechanism of camel milk on the liver tissue of mice. A gut microbiota of the feces of mice and transcriptomic and proteomic analyses of the liver of mice were performed. Analysis of serum and liver biochemical indexes revealed that camel milk not only prevents alcohol-induced colonic dysfunction and lipid accumulation, but also regulates oxidative stress and inflammatory cytokine production to protect against chronic ALD in mouse. The gut microbial community of mice treated with camel milk was more similar to the untreated control group than to the model group, indicating that the intake of camel milk pre- and post-alcohol gavage effectively prevents and alleviates the intestinal microbial disorder caused by chronic alcoholism in mice. Furthermore, the results of the transcriptomic and proteomic analyses of the liver tissue showed that camel milk can improve alcoholic liver injury in mice by regulating inflammatory factors and immune system disruptions. This study provides insights into the molecular mechanism by which camel milk can be developed as a potential functional food with no side effects and against liver injury. [ABSTRACT FROM AUTHOR]

Structural stability and rapid charge–discharge capability of electrode materials are required for high performance lithium-ion batteries (LIBs). The materials derived from polyoxometalates (POMs) show special advantages in inhibiting capacity attenuation, and good dispersion or combination of POMs with metal–organic frameworks (MOFs) is an important method to obtain high activity anode composites for LIBs. In this study, a uniform MoO2/MoS2 heterostructure with surface supported carbon (C-MoO2/MoS2) was successfully fabricated from a [Cu2(BTC)4/3(H2O)2]6[H3PMo12O40] precursor, which showed not only the designed octahedral morphology but also fast charge transfer, long working life, and high rate performance. Superior reversible lithium storage capacity of 1047 mA h g−1 after 300 cycles was obtained at 1 A g−1. Even after 700 cycles at 5 A g−1, the discharge specific capacity of 646 mA h g−1 was maintained, and rate capability of 610 mA h g−1 could be achieved at 10 A g−1. The high capacitive contribution could be explained by the relatively large specific surface area of porous C-MoO2/MoS2, which was mainly caused by the supported carbon network and MoS2 nanosheets, resulting in fast lithiation/delithiation processes. [ABSTRACT FROM AUTHOR]

Background and Aim: The coronavirus disease 2019 pandemic has impacted gastroenterology practices worldwide; however, its protracted effects within Southeast Asia were unknown. The primary aim of the study was to determine the impact of the pandemic on clinical demands including burnout among gastroenterologists within the region. The secondary aim was to identify risk factors for burnout and determine regional stressors. Methods: This was a mixed‐methods study. Gastroenterologists were surveyed electronically between September 1 and December 7, 2020, via gastroenterology and endoscopy societies of Brunei, Indonesia, Malaysia, Philippines, Singapore, and Thailand. Quantitative and qualitative data were collected. The 22‐item Maslach Burnout Inventory‐Human Services Survey (MBI‐HSS) was used to detect burnout. Quantitative data were non‐parametric; non‐parametric methods were used for statistical comparisons. Logistic regression was used to determine risk factors for burnout. Content analysis method was used to analyze qualitative data. Ethical approval was obtained. Results: A total of 73.0% reported that they were still significantly affected by the pandemic. Of these, 40.5% reported increased workload and 59.5% decreased workload. Statistically significant differences in weekly working hours, endoscopy, and inpatient volumes were present. No differences were observed in outpatient volumes, likely because of telemedicine. Burnout was common; however, 50.1% of gastroenterologists were unaware of or did not have access to mental health support. This, as well as depression, being a trainee, and public sector work, increased burnout risk significantly. Conclusion: The effects of the pandemic are multifaceted, and burnout is common among Southeast Asian gastroenterologists. Safeguards for mental health are suboptimal, and improvements are urgently needed. [ABSTRACT FROM AUTHOR]

Background: Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder characterized by abdominal pain, diarrhea or constipation, and changes in defecation patterns. No organic disease is found to explain these symptoms by routine clinical examination. This study aims to investigate the efficacy and safety of acupuncture therapy for IBS patients compared with those of conventional treatments. We also aim to identify the optimal acupoint combination recommended for IBS and to clarify the clinical advantage of the "multiacupoint co-effect and synergistic effect."Methods and Analysis: A total of 204 eligible patients who meet the Rome IV criteria for IBS will be randomly stratified into acupuncture group A, acupuncture group B, or the control group in a 1:1:1 ratio with a central web-based randomization system. The prespecified acupoints used in the control group will include bilateral Tianshu (ST25), Shangjuxu (ST37), Neiguan (PC6), and Zusanli (ST36). The prespecified acupoints used in experimental group A will include bilateral Tianshu (ST25), Shangjuxu (ST37), and Neiguan (PC6). The prespecified acupoints used in experimental group B will include bilateral Tianshu (ST25), Shangjuxu (ST37), and Zusanli (ST36). Each patient will receive 12 acupuncture treatments over 4 weeks and will be followed up for 4 weeks. The primary outcome is the IBS-Symptom Severity Scale (IBS-SSS) score. The secondary outcomes include the Bristol Stool Form Scale (BSFS), Work and Social Adjustment Score (WSAS), IBS-Quality of Life (IBS-QOL), Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS) scores. Both the primary outcome and the secondary outcome measures will be collected at baseline, at 2 and 4 weeks during the intervention, and at 6 weeks and 8 weeks after the intervention.Ethics and Dissemination: The entire project has been approved by the ethics committee of the Beijing University of Chinese Medicine (2020BZYLL0903).Discussion: This is a multicenter randomized controlled trial for IBS in China. The findings may shed light on the efficacy of acupuncture as an alternative to conventional IBS treatment. The results of the trial will be disseminated in peer-reviewed publications.Trial Registration: Chinese Clinical Trials Register ChiCTR2000041215 . First registered on 12 December 2020. http://www.chictr.org.cn/ . [ABSTRACT FROM AUTHOR]

Accurate and efficient empirical potential energy models that describe the atomistic interactions between water molecules in the liquid phase are essential for computer simulations of many problems in physics, chemistry, and biology, especially when long length or time scales are important. However, while models with non-polarizable partial charges at four or five sites in a water molecule give remarkably good values for certain properties, deficiencies have been noted in other properties and increasing the number of sites decreases computational efficiency. An alternate approach is to utilize a multipole expansion of the electrostatic potential due to the molecular charge distribution, which is exact outside the charge distribution in the limits of infinite distances or infinite orders of multipoles while partial charges are a qualitative representation of electron density as point charges. Here, a single-site multipole model of water is presented, which is as fast computationally as three-site models but is also more accurate than four- and five-site models. The dipole, quadrupole, and octupole moments are from quantum mechanical-molecular mechanical calculations so that they account for the average polarization in the liquid phase, and represent both the in-plane and out-of-plane electrostatic potentials of a water molecule in the liquid phase. This model gives accurate thermodynamic, dynamic, and dielectric properties at 298 K and 1 atm, as well as good temperature and pressure dependence of these properties. [ABSTRACT FROM AUTHOR]