Field-Free Manipulation of Two-Dimensional Ferromagnet CrTe2 by Spin-Orbit Torques.

Electrical manipulation of magnetic states in two-dimensional ferromagnetic systems is crucial in information storage and low-dimensional spintronics. Spin-orbit torque presents a rapid and energy-efficient method for electrical control of the magnetization. In this letter, we demonstrate a wafer-scale spin-orbit torque switching of two-dimensional ferromagnetic states. Using molecular beam epitaxy, we fabricate two-dimensional heterostructures composed of low crystal-symmetry WTe2 and ferromagnet CrTe2 with perpendicular anisotropy. By utilizing out-of-plane spins generated from WTe2, we achieve field-free switching of the CrTe2 perpendicular magnetization. The threshold switching current density in CrTe2/WTe2 is 1.2 × 106 A/cm2, 20 times smaller than that of the CrTe2/Pt control sample even with an external magnetic field. In addition, the switching behavior can be modulated by external magnetic fields and crystal symmetry. Our findings demonstrate a controllable and all-electric manipulation of perpendicular magnetization in a two-dimensional ferromagnet, representing a significant advancement toward the practical implementation of low-dimensional spintronic devices.

Scoping review: Exploring the relationship between chrononutrition and glycemic responses in the adult population.

Chrononutrition, an emerging body of evidence on the relationship between biological rhythms and metabolism, has been established to be associated with glycemic responses. However, the available evidence is inconsistent, due to protocol variations. Therefore, this review aims to summarize the findings on chrononutrition characteristics and their association with glycemic responses among adults. Systematic searches were conducted across six databases (PubMed, EBSCO Host, ProQuest Central, MEDLINE & Ovid, Scopus and Web of Science) to identify all relevant studies published from January 2012. Two reviewers independently screened the abstracts and full-text articles based on the inclusion and exclusion criteria. Details about population characteristics, study methods and key findings were extracted following the PRISMA-ScR guideline. The quality of selected studies was evaluated using the mixed methods appraisal tool. The searchers identified 49 studies eligible for analysis. The results showed that meal timing, particularly night-time eating and snacking were associated with glycemic responses. Regarding meal regularity, skipping breakfast may affect glycemic responses, but no clear conclusion was drawn about its effect on insulin. The association between meal frequency and glycemic responses was inconclusive. Night fasting duration and restricted eating window are potentially associated with glycemic responses. The current review extensively investigates the association between chrononutrition factors and glycemic responses in adults. However, more prospective cohort and interventional studies are needed to better understand this causal-effect relationship.

Androgen Receptor Splice Variant 7 in Asian Patients With Metastatic Castration-Resistant Prostate Cancer.

PURPOSE: Androgen receptor splice variant 7 (ARV-7) is a resistance mechanism to hormonal therapy in metastatic castrate-resistant prostate cancer (mCRPC). It has been associated with poor outcomes. On progression to castrate resistance, ARV-7 positivity has been identified in global populations at an incidence of 17.8%-28.8%. Here, we characterize the incidence of ARV-7 positivity in Asian patients with mCRPC in a prospective fashion and evaluate its implications on treatment outcomes. METHODS: Patients with mCRPC from multiple centers in Southeast and East Asia were enrolled in a prospective manner before initiation of androgen receptor signaling inhibitors or docetaxel. ARV-7 status was evaluated at baseline with three commercially available assays: AdnaTest Prostate Cancer platform, Clearbridge method, and IBN method. Clinical outcomes at progression were assessed. The primary end point of this study was prevalence of ARV-7 positivity; secondary end points were incidence of ARV-7 positivity, prostate specific antigen (PSA) response rate, PSA progression-free survival (PFS), and overall survival (OS). RESULTS: A total of 102 patients with a median age of 72 years at enrollment participated. Overall, an incidence of ARV-7 positivity of between 14.3% and 33.7% in Asian patients with mCRPC was demonstrated depending on the assay used. Patients found to have ARV-7 positivity at enrollment had a numerically worse PSA PFS compared with ARV-7 negative patients. CONCLUSION: In this study, the incidence of ARV-7 positivity in Asian patients with mCRPC was shown to be similar to the global population. Patients with ARV-7 positivity appear to have more aggressive disease with numerically worse PSA PFS and OS. Further prospective studies are needed to fully characterize the relationship that ARV-7 positivity has on prognosis of Asian patients with mCRPC.

Sex-specific effects of maternal blood pressure on newborn telomere length: A prospective study.

OBJECTIVE: To investigate the relationship between maternal blood pressure (BP) and neonatal cord blood telomere length (TL) during pregnancy, and to clarify the sensitive period. METHODS: We conducted a prospective cohort study with 621 mother-newborn pairs from the Guangxi Zhuang Birth Cohort (GZBC) in China. Multiple informant models, restricted cubic spline regression (RCS) models, and quantile regression models were conducted to analyze the correlation between maternal BP and neonatal TL. RESULTS: Maternal diastolic blood pressure (DBP) was inversely related to neonatal cord blood TL in the second trimester (P = 0.015) and the third trimester (P = 0.011). There was a male-specific relationship between maternal BP and neonatal TL. A 1 mmHg increment in maternal systolic blood pressure (SBP) and DBP during the second trimester was related with 0.42% (95% CI: -0.80%, -0.04%) and 0.61% (95% CI: -1.13%, -0.09%) shorter TL in male newborns, respectively. Per unit increase of maternal DBP during the third trimester was related with 0.54% (95% CI: -1.03%, -0.05%) shorter TL in male newborns. Pregnant women with hypertensive disease of pregnancy (HDP) had male offspring with shorter TL (P = 0.003). However, no significant relationships were found in female newborns (P = 0.570). CONCLUSION: Maternal BP during pregnancy is inversely correlated with male neonatal TL and the second and third trimesters are sensitive windows.

Softening the tumor matrix through cholesterol depletion breaks the physical barrier for enhanced antitumor therapy.

The tumor develops defense tactics, including conversing the mechanical characteristics of tumor cells and their surrounding environment. A recent study reported that cholesterol depletion stiffens tumor cells, which could enhance adaptive T-cell immunotherapy. However, it remains unclear whether reducing the cholesterol in tumor cells contributes to re-educating the stiff tumor matrix, which serves as a physical barrier against drug penetration. Herein, we found that depleting cholesterol from tumor cells can demolish the intratumor physical barrier by disrupting the mechanical signal transduction between tumor cells and the extracellular matrix through the destruction of lipid rafts. This disruption allows nanoparticles (H/S@hNP) to penetrate deeply, resulting in improved photodynamic treatment. Our research also indicates that cholesterol depletion can inhibit the epithelial-mesenchymal transition and repolarize tumor-associated macrophages from M2 to M1, demonstrating the essential role of cholesterol in tumor progression. Overall, this study reveals that a cholesterol-depleted, softened tumor matrix reduces the difficulty of drug penetration, leading to enhanced antitumor therapeutics.

Impact of acute glycemic variability on short-term outcomes in patients with ST-segment elevation myocardial infarction: a multicenter population-based study.

BACKGROUND: Given the increasing attention to glycemic variability (GV) and its potential implications for cardiovascular outcomes. This study aimed to explore the impact of acute GV on short-term outcomes in Chinese patients with ST-segment elevation myocardial infarction (STEMI). METHODS: This study enrolled 7510 consecutive patients diagnosed with acute STEMI from 274 centers in China. GV was assessed using the coefficient of variation of blood glucose levels. Patients were categorized into three groups according to GV tertiles (GV1, GV2, and GV3). The primary outcome was 30-day all-cause death, and the secondary outcome was major adverse cardiovascular events (MACEs). Cox regression analyses were conducted to determine the independent correlation between GV and the outcomes. RESULTS: A total of 7136 patients with STEMI were included. During 30-days follow-up, there was a significant increase in the incidence of all-cause death and MACEs with higher GV tertiles. The 30-days mortality rates were 7.4% for GV1, 8.7% for GV2 and 9.4% for GV3 (p = 0.004), while the MACEs incidence rates was 11.3%, 13.8% and 15.8% for the GV1, GV2 and GV3 groups respectively (p < 0.001). High GV levels during hospitalization were significantly associated with an increased risk of 30-day all-cause mortality and MACEs. When analyzed as a continuous variable, GV was independently associated with a higher risk of all-cause mortality (hazard ratio [HR] 1.679, 95% confidence Interval [CI] 1.005-2.804) and MACEs (HR 2.064, 95% CI 1.386-3.074). Additionally, when analyzed as categorical variables, the GV3 group was found to predict an increased risk of MACEs, irrespective of the presence of diabetes mellitus (DM). CONCLUSION: Our study findings indicate that a high GV during hospitalization was significantly associated with an increased risk of 30-day all-cause mortality and MACE in Chinese patients with STEMI. Moreover, acute GV emerged as an independent predictor of increased MACEs risk, regardless of DM status.

Of Rodents and Primates: Time-Variant Gain in Drift-Diffusion Decision Models.

Sequential sampling models of decision-making involve evidence accumulation over time and have been successful in capturing choice behaviour. A popular model is the drift-diffusion model (DDM). To capture the finer aspects of choice reaction times (RTs), time-variant gain features representing urgency signals have been implemented in DDM that can exhibit slower error RTs than correct RTs. However, time-variant gain is often implemented on both DDM's signal and noise features, with the assumption that increasing gain on the drift rate (due to urgency) is similar to DDM with collapsing decision bounds. Hence, it is unclear whether gain effects on just the signal or noise feature can lead to a different choice behaviour. This work presents an alternative DDM variant, focusing on the implications of time-variant gain mechanisms, constrained by model parsimony. Specifically, using computational modelling of choice behaviour of rats, monkeys, and humans, we systematically showed that time-variant gain only on the DDM's noise was sufficient to produce slower error RTs, as in monkeys, while time-variant gain only on drift rate leads to faster error RTs, as in rodents. We also found minimal effects of time-variant gain in humans. By highlighting these patterns, this study underscores the utility of group-level modelling in capturing general trends and effects consistent across species. Thus, time-variant gain on DDM's different components can lead to different choice behaviours, shed light on the underlying time-variant gain mechanisms for different species, and can be used for systematic data fitting. Supplementary Information: The online version contains supplementary material available at 10.1007/s42113-023-00194-1.

Exosomal circ_0032704 confers sorafenib resistance to hepatocellular carcinoma and contributes to cancer malignant progression by modulating the miR-514a-3p/PD-L1 pathway.

Purpose: This study aims to explore the role of circ_0032704 in sorafenib-resistant hepatocellular carcinoma (HCC). Methods: The expression of circ_0032704, miR-514a-3p, and programmed death-ligand 1 (PD-L1) mRNA was detected by quantitative real-time PCR (qPCR). The expression of multidrug resistant-related proteins, migration/invasion-related proteins, exosome-related proteins, and PD-L1 protein was detected by western blot. Cell viability was detected by CCK-8 assay. Cell proliferation, migration, and invasion were assessed by EdU assay, wound healing assay, and transwell assay. The binding between miR-514a-3p and circ_0032704 or PD-L1 was verified by RIP assay, pull-down assay, and dual-luciferase reporter assay. Cell- or serum-derived exosomes were isolated and identified by TEM and NTA. Xenograft models were established to determine the effect of circ_0032704 on drug resistance in vivo. Results: Circ_0032704 was overexpressed in sorafenib-resistant HCC tissues and cells. Circ_0032704 knockdown reduced sorafenib resistance in HCC cells and inhibited cell proliferation, migration, and invasion of sorafenib-resistant HCC cells, while these effects were reversed by PD-L1 overexpression. We found that circ_0032704 positively regulated PD-L1 expression via targeting miR-514a-3p. Exosomes with circ_0032704 inhibition reduced sorafenib resistance in HCC cells and inhibited cell proliferation, migration, and invasion of sorafenib-resistant HCC cells. Exosomes with circ_0032704 inhibition also inhibited tumor growth in vivo. The expression of circ_0032704 in exosomes was stable and possessed diagnostic value. Conclusion: Circ_0032704 enhanced sorafenib resistance in HCC and promoted the malignant development of sorafenib-resistant HCC. Circ_0032704 could be transported by exosomes, and exosomal circ_0032704 had diagnostic value.

A fresh-cut papaya freshness prediction model based on partial least squares regression and support vector machine regression.

This study investigated the physicochemical and flavor quality changes in fresh-cut papaya that was stored at 4 °C. Multivariate statistical analysis was used to evaluate the freshness of fresh-cut papaya. Aerobic plate counts were selected as a predictor of freshness of fresh-cut papaya, and a prediction model for freshness was established using partial least squares regression (PLSR), and support vector machine regression (SVMR) algorithms. Freshness of fresh-cut papaya could be well distinguished based on physicochemical and flavor quality analyses. The aerobic plate counts, as a predictor of freshness of fresh-cut papaya, significantly correlated with storage time. The SVMR model had a higher prediction accuracy than the PLSR model. Combining flavor quality with multivariate statistical analysis can be effectively used for evaluating the freshness of fresh-cut papaya.

Original investigation: manipulating energy availability in male endurance runners: a randomised controlled trial.

This study investigated the effect of 4 days low energy availability (LEA) on physiological markers and mood states in male endurance runners. Twelve participants (mean (standard deviation); age: 25.8 (3.8) years; fat-free mass (FFM): 52.8 (5.5) kg) completed three 4-day conditions: adequate energy availability (AEA): 45 kcal/kg FFM/day; LEA1: 30 kcal/kg FFM/day; and LEA2: 15 kcal/kg FFM/day, in a randomized order. Participants ran on a treadmill at 65% of V̇O2max until they expended 15 kcal/kg FFM/day of energy. Energy intake was adjusted to achieve the desired energy availability. Pre- and post-measurements of bone turnover, metabolism, testosterone and estradiol (plasma), resting metabolic rate (indirect calorimetry), and mood states (Brunel Mood Scale) were assessed. The results reported a significant decrease in testosterone (condition × time interaction, p = 0.03) occurred on LEA2 (Pre: 23.8 (7.0) nmol/L vs. Post: 20.3 (7.7) nmol/L) compared with AEA (Pre: 22.9 (5.5) nmol/L vs. Post: 23.3 (6.1) nmol/L) or LEA1 (Pre: 23.6 (8.6) nmol/L vs. Post: 20.9 (8.8) nmol/L). Fatigue level significantly increased (condition × time interaction, p = 0.02) in LEA2 (Pre: 3.5 (1.7) vs. Post: 6.5 (2.9)) but did not change in AEA (Pre: 2.8 (1.5) vs. Post: 2.5 (2.7)) or LEA1 (Pre: 2.8(2.4) vs. Post: 2.9 (2.0)). Other measures were unaffected by the interventions. In conclusion, this study suggests that testosterone and fatigue may serve as early indicators of LEA in male runners. However, other physiological markers and mood states appeared largely unaffected, aligning with existing literature indicating minimal disruption of physiological functions during acute LEA in male athletes. Study registration: Australian New Zealand Clinical Trials Registry (Trial No.: 381278).

Electroconvulsive Therapy in Refractory and Super-Refractory Status Epilepticus in Adults: A Scoping Review.

BACKGROUND: Electroconvulsive therapy (ECT) has been suggested as a treatment option for refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE). OBJECTIVE: The objective of this scoping review was to conduct an extensive literature review on the role of ECT as a treatment option for RSE and SRSE. METHODS: We searched Ovid MEDLINE and Scopus for journal articles from database inception until February 2024. Articles were then selected based on predetermined inclusion and exclusion criteria. RESULTS: We identified five retrospective case series with 28 adult patients receiving ECT for RSE or SRSE. ECT was administered within 3-70 days (mean 20 days) after the development of SE, and the mean number of ECT courses ranged from 1 to 12 sessions for each patient. ECT was administered in fixed or titrated doses. A total of 20 out of 28 patients (71%) showed clinical improvement, with two (7%) having complete cessation of seizures. It is essential to note that given the lack of control, there could be overreporting of clinical improvement in these studies. 11 patients (39%) were reported as deceased due to causes that were not directly related to ECT treatment. Four patients (14%) reported adverse effects of ECT, including memory, concentration, and/or cognitive impairment. CONCLUSIONS: There are level-4 Oxford Centre for Evidence-Based Medicine evidence and low-level Grading of Recommendations Assessment Development and Education evidence that suggest ECT as a treatment option for RSE and SRSE. In light of the limitations of the existing evidence, clinicians should carefully consider individual patients' clinical contexts when deciding on the appropriateness of ECT as a treatment option. Further research, including prospective studies with controlled designs, is needed to elucidate the efficacy, safety, and optimal regime of ECT in the management of RSE and SRSE.

Linear Electro-Optic Effect in 2D Ferroelectric for Electrically Tunable Metalens.

The advent of 2D ferroelectrics, characterized by their spontaneous polarization states in layer-by-layer domains without the limitation of a finite size effect, brings enormous promise for applications in integrated optoelectronic devices. Comparing with semiconductor/insulator devices, ferroelectric devices show natural advantages such as non-volatility, low energy consumption and high response speed. Several 2D ferroelectric materials have been reported, however, the device implementation particularly for optoelectronic application remains largely hypothetical. Here, the linear electro-optic effect in 2D ferroelectrics is discovered and electrically tunable 2D ferroelectric metalens is demonstrated. The linear electric-field modulation of light is verified in 2D ferroelectric CuInP2S6. The in-plane phase retardation can be continuously tuned by a transverse DC electric field, yielding an effective electro-optic coefficient rc of 20.28 pm V-1. The CuInP2S6 crystal exhibits birefringence with the fast axis oriented along its (010) plane. The 2D ferroelectric Fresnel metalens shows efficacious focusing ability with an electrical modulation efficiency of the focusing exceeding 34%. The theoretical analysis uncovers the origin of the birefringence and unveil its ultralow light absorption across a wide wavelength range in this non-excitonic system. The van der Waals ferroelectrics enable room-temperature electrical modulation of light and offer the freedom of heterogeneous integration with silicon and another material system for highly compact and tunable photonics and metaoptics.

Incidence and predictors of posttraumatic epilepsy and cognitive impairment in patients with traumatic brain injury: A retrospective cohort study in Malaysia.

OBJECTIVE: Posttraumatic epilepsy (PTE) significantly impacts morbidity and mortality, yet local PTE data remain scarce. In addition, there is a lack of evidence on cognitive comorbidity in individuals with PTE in the literature. We sought to identify potential PTE predictors and evaluate cognitive comorbidity in patients with PTE. METHODS: A 2-year retrospective cohort study was employed, in which adults with a history of admission for traumatic brain injury (TBI) in 2019 and 2020 were contacted. Three hundred one individuals agreed to participate, with a median follow-up time of 30.75 months. The development of epilepsy was ascertained using a validated tool and confirmed by our neurologists during visits. Clinical psychologists assessed the patients' cognitive performance. RESULTS: The 2-year cumulative incidence of PTE was 9.3% (95% confidence interval [CI] 5.9-12.7). The significant predictors of PTE were identified as a previous history of brain injury [hazard ratio [HR] 4.025, p = .021], and intraparenchymal hemorrhage (HR: 2.291, p = .036), after adjusting for other confounders. TBI patients with PTE performed significantly worse on the total ACE-III cognitive test (73.5 vs 87.0, p = .018), CTMT (27.5 vs 33.0, p = .044), and PSI (74.0 vs 86.0, p = .006) than TBI patients without PTE. A significantly higher percentage of individuals in the PTE group had cognitive impairment, compared to the non-PTE group based on ACE-III (53.6% vs 46.4%, p = .001) and PSI (70% vs 31.7%, p = .005) scores at 2 years post-TBI follow-up. SIGNIFICANCE: This study emphasizes the link between TBI and PTE and the chance of developing cognitive impairment in the future. Clinicians can target interventions to prevent PTE by identifying specific predictors, which helps them make care decisions and develop therapies to improve patients' quality of life.

Fatal COVID-19 pulmonary disease involves ferroptosis.

SARS-CoV-2 infection causes severe pulmonary manifestations, with poorly understood mechanisms and limited treatment options. Hyperferritinemia and disrupted lung iron homeostasis in COVID-19 patients imply that ferroptosis, an iron-dependent cell death, may occur. Immunostaining and lipidomic analysis in COVID-19 lung autopsies reveal increases in ferroptosis markers, including transferrin receptor 1 and malondialdehyde accumulation in fatal cases. COVID-19 lungs display dysregulation of lipids involved in metabolism and ferroptosis. We find increased ferritin light chain associated with severe COVID-19 lung pathology. Iron overload promotes ferroptosis in both primary cells and cancerous lung epithelial cells. In addition, ferroptosis markers strongly correlate with lung injury severity in a COVID-19 lung disease model using male Syrian hamsters. These results reveal a role for ferroptosis in COVID-19 pulmonary disease; pharmacological ferroptosis inhibition may serve as an adjuvant therapy to prevent lung damage during SARS-CoV-2 infection.

Protective Effect of Hop Ethyl Acetate Extract on Corticosterone-Induced PC12 and Improvement of Depression-like Behavior in Mice.

Depression is a common mental disorder. In recent years, more and more attention has been paid to depression and its etiology and pathogenesis. This review aims to explore the neuroprotective and antidepressant effects of hop components. By establishing an in vitro cell damage model using PC12 cells induced by corticosterone (CORT) and an in vivo depression model through the intracranial injection of lipopolysaccharide (LPS) in mice, hop ethyl acetate extract (HEA) was used to study the protective effect and mechanism of HEA on neuronal cells in vitro and the antidepression effect and mechanism in vivo. The results showed that HEA increased the survival and decreased the rate of lactate dehydrogenase (LDH) release, apoptosis, and the ROS and NO content of CORT-induced PC12 cells. HEA alleviated depressive-like behavior, neuroinflammation, reduction of norepinephrine, and dendritic spines induced by intracerebroventricular injection of LPS in mice and increases the expression levels of BDNF, SNAP 25, and TrkB proteins without any significant side effects or toxicity. Hops demonstrated significant comprehensive utilization value, and this work provided an experimental basis for the role of hops in the treatment of depression and provided a basis for the development of HEA for antidepressant drugs or dietary therapy products.

Patient- and caregiver-related factors affecting family caregiver burden of urologic cancer patients.

OBJECTIVE: This study aimed to investigate the level of family caregivers' (FC) burden and the extent to which patient- and caregiver-related factors influence the caregiving burden among FCs of urologic cancer (UC) patients. METHOD: A cross-sectional survey was conducted on caregivers of UC patients who sought cancer care. The modified caregiver strain index (MCSI) was used to assess FC burden. RESULTS: Just over half (54.3%) of FCs had moderate/high MCSI scores (score 9-26). By demographics, FCs who were unemployed (OR = 5.55, 95%CI 1.50-20.60) and perceived their current health condition as moderate/poor (OR = 6.05, 95%CI 1.95-18.78) reported higher odds of increased FC burden. Patient performance status played a pivotal role in exacerbating FC burden, whereby the odds of higher FC burden was 13 times higher in caregivers of UC patients having an Eastern Cooperative Oncology Group (ECOG) performance rating score of 3-4 (OR = 13.06, 95%CI 1.44-111.26) than those with a score of 0. Perceived lower levels of confidence in care provision were significantly associated with a higher level of strain (OR = 6.76, 985%CI 1.02-44.90). CONCLUSION: Care recipient performance status was a strong patient-related factor associated with higher FC burden regardless of duration of caregiving and other caregiver-related factors after adjusting for caregiver demographics.

Testing the Efficacy of a Brief, Self-Guided Mindfulness Ecological Momentary Intervention on Emotion Regulation and Self-Compassion in Social Anxiety Disorder: Randomized Controlled Trial.

BACKGROUND: Theories propose that brief, mobile, self-guided mindfulness ecological momentary interventions (MEMIs) could enhance emotion regulation (ER) and self-compassion. Such changes are posited to be mechanisms of change. However, rigorous tests of these theories have not been conducted. OBJECTIVE: In this assessor-blinded, parallel-group randomized controlled trial, we aimed to test these theories in social anxiety disorder (SAD). METHODS: Participants with SAD (defined as having a prerandomization cut-off score ≥20 on the Social Phobia Inventory self-report) were randomized to a 14-day fully self-guided MEMI (96/191, 50.3%) or self-monitoring app (95/191, 49.7%) arm. They completed web-based self-reports of 6 clinical outcome measures at prerandomization, 15-day postintervention (administered the day after the intervention ended), and 1-month follow-up time points. ER and self-compassion were assessed at preintervention and 7-day midintervention time points. Multilevel modeling determined the efficacy of MEMI on ER and self-compassion domains from pretrial to midintervention time points. Bootstrapped parallel multilevel mediation analysis examined the mediating role of pretrial to midintervention ER and self-compassion domains on the efficacy of MEMI on 6 clinical outcomes. RESULTS: Participants demonstrated strong compliance, with 78% (149/191) engaging in at least 80% of the MEMI and self-monitoring prompts. MEMI was more efficacious than the self-monitoring app in decreasing ER goal-directed behavior difficulties (between-group Cohen d=-0.24) and lack of emotional clarity (Cohen d=0.16) and increasing self-compassion social connectedness (Cohen d=0.19), nonidentification with emotions (Cohen d=0.16), and self-kindness (Cohen d=0.19) from pretrial to midintervention time points. The within-group effect sizes from pretrial to midintervention were larger in the MEMI arm than in the self-monitoring app arm (ER goal-directed behavior difficulties: Cohen d=-0.73 vs -0.29, lack of emotional clarity: Cohen d=-0.39 vs -0.21, self-compassion domains of social connectedness: Cohen d=0.45 vs 0.19, nonidentification with emotions: Cohen d=0.63 vs 0.48, and self-kindness: Cohen d=0.36 vs 0.10). Self-monitoring, but not MEMI, alleviated ER emotional awareness issues (between-group Cohen d=0.11 and within-group: Cohen d=-0.29 vs -0.13) and reduced self-compassion acknowledging shared human struggles (between-group Cohen d=0.26 and within-group: Cohen d=-0.23 vs 0.13). No ER and self-compassion domains were mediators of the effect of MEMI on SAD symptoms (P=.07-<.99), generalized anxiety symptoms (P=.16-.98), depression severity (P=.20-.94), repetitive negative thinking (P=.12-.96), and trait mindfulness (P=.18-.99) from pretrial to postintervention time points. Similar nonsignificant mediation effects emerged for all of these clinical outcomes from pretrial to 1-month follow-up time points (P=.11-.98). CONCLUSIONS: Brief, fully self-guided, mobile MEMIs efficaciously increased specific self-compassion domains and decreased ER difficulties associated with goal pursuit and clarity of emotions from pretrial to midintervention time points. Higher-intensity MEMIs may be required to pinpoint the specific change mechanisms in ER and self-compassion domains of SAD. TRIAL REGISTRATION: Open Science Framework (OSF) Registries; osf.io/m3kxz https://osf.io/m3kxz.

Synthesis, Screening, and Evaluation of Theranostic Molecular CPCR4-Based Probe Targeting CXCR4.

Chemokines and chemokine receptors are indispensable to play a key role in the development of malignant tumors. As one of the most widely expressed chemokine receptors, chemokine (C-X-C motif) receptor 4 (CXCR4) has been a popular research focus. In most tumors, CXCR4 expression is significantly upregulated. Moreover, integrated nuclide diagnosis and therapy targeting CXCR4 show great potential. [68Ga]Ga-pentixafor, a radioligand targeting CXCR4, exhibits a strong affinity for CXCR4 both in vivo and in vitro. However, [177Lu]Lu-pentixather, the therapeutic companion of [68Ga]Ga-pentixafor, requires significant refinement to mitigate its pronounced hepatic biodistribution. The objective of this study was to synthesize theranostic molecular tracers with superior CXCR4 targeting functions. The Daudi cell line, which highly expressed CXCR4, and the MM.1S cell line, which weakly expressed CXCR4, were used in this study. Based on the pharmacophore cyclo (-d-Tyr-n-me-d-Orn-l-Arg-L-2-NAL-Gly-) (CPCR4) of pentixafor, six tracers were synthesized: [124I]I-1 ([124I]I-CPCR4), [99mTc]Tc-2 ([99mTc]Tc-HYNIC-CPCR4), [124I]I-3 ([124I]I-pentixafor), [18F]AlF-4 ([18F]AlF-NETA-CPCR4), [99mTc]Tc-5 ([99mTc]Tc-MAG3-CPCR4) and [124I]I-6 ([124I]I-pentixafor-Ga) and their radiochemical purities were all higher than 95%. After positron emission tomography (PET)/single-photon emission computed tomography (SPECT) imaging, the [124I]I-6 group exhibited the best target-nontarget ratio. At the same time, comparing the [68Ga]Ga-pentixafor group with the [124I]I-6 group, we found that the [124I]I-6 group had a better target-nontarget ratio and lower uptake in nontarget organs. Therefore, compound 6 was selected for therapeutic radionuclide (131I) labeling, and the tumor-bearing animal models were treated with [131I]I-6. The volume of the tumor site was significantly reduced in the treatment group compared with the control group, and no significant side effects were found. [124I]I-6 and [131I]I-6 showed excellent affinity for targeting CXCR4, and they showed great potential for the integrated diagnosis and treatment of tumors with high CXCR4 expression.

Is a brief mindfulness ecological momentary intervention more efficacious than a self-monitoring app for social anxiety disorder? A randomized controlled trial.

Despite their proliferation, limited knowledge exists regarding possible benefits of brief mindfulness ecological momentary interventions (MEMIs) for social anxiety disorder (SAD). Propositions that MEMIs could alleviate SAD symptoms and related clinical outcomes remain untested. This trial evaluated a 14-day MEMI for SAD. Participants with self-reported SAD were randomized to MEMI (n = 96) or self-monitoring app (SM; n = 95). Whereas MEMI instructed mindfulness exercises, SM prompted only self-monitoring five times daily for 14 days. Participants completed state-level self-reports of depression, anxiety, and mindfulness pre-post-mindfulness practice and SAD symptoms, worry, depression severity, repetitive negative thinking, and trait mindfulness at pre-randomization, post-intervention, and 1-month follow-up (1MFU). Hierarchical linear modeling was conducted. The MEMI yielded statistically significantly larger improvements in momentary depression, anxiety, and mindfulness (Cohen's d = -0.10-0.11). Although no between-group effects emerged in alleviating SAD fear and avoidance, excessive worry, depression severity, repetitive negative thinking, and trait mindfulness (-0.13-0.15), within-group effects were significantly small-to-large from pre-post and pre-1MFU (-4.62-0.67). A significant reduction in depression severity occurred in MEMI (-0.63--0.60) but not SM (-0.31--0.29). Brief MEMI and SM yielded nondifferent sustained effects on SAD, comorbid symptoms, and risk factors, highlighting its potential value within stepped-care delivery settings.