Search

Hexavalent chromium, Cr(VI), is a ubiquitous toxic metal that can be reduced to Cr(III) by nano-zero-valent iron (nZVI). Finding out effects of continuous rainfall leaching on the Cr(VI) release and availability remains a problem, needing to be addressed. Whether the Cr(VI) reduction by nZVI and continuous rainfall leaching lead to localized heterogeneity in soil is unclear. Therefore, two in situ high-resolution (HR) techniques of the diffusive gradients in thin-films (DGT) and planar optode were combined with ex situ sampling experiments here. Results demonstrate that nZVI decreased Cr(VI) leaching by 5.60-8.50 % compared to control soils. DGT-measured concentrations of Cr(VI), C DGT -Cr(VI), ranged from 7.31 to 19.4 μg L -1 in the control soils, increasing with depth while C DGT -Cr(VI) in nZVI-treated soils (2.41-6.18 μg L -1 ) decreased or remained stable with depth. However, simulated acid-rain leaching increases C DGT -Cr(VI) by 1.61-fold in nZVI-treated soils, negatively affecting the remediation. DGT measurements in bulk soils using disc devices are better at capturing the change of Cr(VI) availability at different conditions, whereas 2D-HR DGT mappings did not characterize significant mobilization of Cr(VI) at the micro-scale. These findings emphasize the importance of monitoring Cr(VI) release and availability in remediated soil under acid-rain leaching conditions for effective environment management., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A new microsporidian disease of the pond-reared ridgetail white prawn, Palaemon carinicauda, was found in China. Light microscopy, pathology, and scanning electron microscopy showed that the parasite infected the host's skeletal muscle tissue and formed spherical sporophorous vesicles (SPOVs). Electron microscopy revealed that its merogonic life stages developed in direct contact with the host cytoplasm. The sporogonic life stages underwent octosporoblastic sporogony with the formation of eight uninucleate spores in each SPOV. Fresh SPOVs were 5.4 ± 0.55 µm in diameter. The octospores were oval and measured 2.3 × 1.5 μm (fresh) and 1.96 × 1.17 μm (fixed). The isofilar polar filament was coiled with 9-10 turns and arranged in two rows. Phylogenetic analysis based on the SSU rRNA gene suggests that this microsporidium has close affinities with members of the genera Potaspora and Apotaspora, but represents an independent generic taxon. We therefore propose the establishment of a new genus and species (Paospora carinifang n. gen., n. sp.) within the family Spragueidae. We also propose a taxonomic revision to transfer Potaspora macrobrachium to this new genus and reclassify it as Paospora macrobrachium comb. nov., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Dual inhibition of vascular endothelial growth factor and epidermal growth factor receptor (EGFR) signaling pathways offers the prospect of improving the effectiveness of EFGR-targeted therapy. In this phase 3 study (ClinicalTrial.gov: NCT04028778), 315 patients with treatment-naïve, EGFR-mutated, advanced non-small cell lung cancer (NSCLC) were randomized (1:1) to receive anlotinib or placebo plus gefitinib once daily on days 1-14 per a 3-week cycle. At the prespecified final analysis of progression-free survival (PFS), a significant improvement in PFS was observed for the anlotinib arm over the placebo arm (hazards ratio [HR] = 0.64, 95% CI, 0.48-0.80, P = 0.003). Particularly, patients with brain metastasis and those harboring EGFR amplification or high tumor mutation load gained significant more benefits in PFS from gefitinib plus anlotinib. The incidence of grade 3 or higher treatment-emergent adverse events was 49.7% of the patients receiving gefitinib plus anlotinib versus 31.0% of the patients receiving gefitinib plus placebo. Anlotinib plus gefitinib significantly improves PFS in patients with treatment-naïve, EGFR-mutated, advanced NSCLC, with a manageable safety profile., (© 2024. The Author(s).)

The diagnosis and treatment of pulmonary hypertension have changed dramatically through the re-defined diagnostic criteria and advanced drug development in the past decade. The application of Artificial Intelligence for the detection of elevated pulmonary arterial pressure (ePAP) was reported recently. Artificial Intelligence (AI) has demonstrated the capability to identify ePAP and its association with hospitalization due to heart failure when analyzing chest X-rays (CXR). An AI model based on electrocardiograms (ECG) has shown promise in not only detecting ePAP but also in predicting future risks related to cardiovascular mortality. We aimed to develop an AI model integrating ECG and CXR to detect ePAP and evaluate their performance. We developed a deep-learning model (DLM) using paired ECG and CXR to detect ePAP (systolic pulmonary artery pressure > 50 mmHg in transthoracic echocardiography). This model was further validated in a community hospital. Additionally, our DLM was evaluated for its ability to predict future occurrences of left ventricular dysfunction (LVD, ejection fraction < 35%) and cardiovascular mortality. The AUCs for detecting ePAP were as follows: 0.8261 with ECG (sensitivity 76.6%, specificity 74.5%), 0.8525 with CXR (sensitivity 82.8%, specificity 72.7%), and 0.8644 with a combination of both (sensitivity 78.6%, specificity 79.2%) in the internal dataset. In the external validation dataset, the AUCs for ePAP detection were 0.8348 with ECG, 0.8605 with CXR, and 0.8734 with the combination. Furthermore, using the combination of ECGs and CXR, the negative predictive value (NPV) was 98% in the internal dataset and 98.1% in the external dataset. Patients with ePAP detected by the DLM using combination had a higher risk of new-onset LVD with a hazard ratio (HR) of 4.51 (95% CI: 3.54-5.76) in the internal dataset and cardiovascular mortality with a HR of 6.08 (95% CI: 4.66-7.95). Similar results were seen in the external validation dataset. The DLM, integrating ECG and CXR, effectively detected ePAP with a strong NPV and forecasted future risks of developing LVD and cardiovascular mortality. This model has the potential to expedite the early identification of pulmonary hypertension in patients, prompting further evaluation through echocardiography and, when necessary, right heart catheterization (RHC), potentially resulting in enhanced cardiovascular outcomes., (© 2024. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Current knowledge about public climate change perception mainly covers belief, concern, and attitudes. However, how this discourse is interpreted using individuals' own frame of reference remains largely unknown, particularly in many large emitters from non-Annex I countries such as China. This study, for the first time, performs a nationwide open-ended survey covering 4,037 respondents and collected 12,100 textual answers. Using a semiautomated coding method, we find seven mental images that exclusively represent the Chinese interpretation of the climate change issue, including global warming, distant icons, natural disasters, environmental degradation, cause, solution, and weather. Analysis of influencing factors shows that females, those with lower education levels, lower income, and older individuals tend to connect climate change with natural weather phenomena. Younger and well-educated residents in developed cities are more aware of various consequences and anthropogenic causes of climate change. People with stronger climate change beliefs, policy support, and personal experience of extreme weather are more likely to mention disastrous impacts, carbon emission as causes, and potential solutions. Employing the multilevel regression and post-stratification technique, we map the prevalence of mental images in China at the prefecture-city level. The results reveal significant geographical heterogeneity, with estimated national means ranging from a high of 55% (weather) to a low of 11% (solution). Our findings reveal diverse perspectives and a widespread misconception of climate change in China, suggesting the need for tailored clarification strategies to gain public consent., (© 2024 Society for Risk Analysis.)

Background: The relationship between serum uric acid (SUA) levels and brain-related health remains uncertain., Objectives: This study aimed to investigate the relationship between SUA levels and some neurodegenerative disorders and brain structure., Design: A longitudinal study., Setting and Participants: 384,517 participants who did not have stroke, dementia, and Parkinsonism, with complete urate testes and covariates were included., Measurements: Cox proportional hazards models, competing risk models, and restricted cubic spine models were applied., Results: During the median follow-up time of 12.7 years (interquartile range [IQR]:12.0, 13.5), 7821 (2.0%) participants developed stroke, 5103 (1.3%) participants developed dementia, and 2341 (0.6%) participants developed Parkinsonism. Nonlinear relationships were identified between SUA levels and stroke (J-shaped), dementia, and Parkinsonism (U-shaped). SUA levels of 4.2 mg/dl, 6.4 mg/dl, and 6.6 mg/dl yielded the lowest risk of stroke, dementia, and Parkinsonism, respectively. Besides, we found high SUA levels reduced the volumes of total brain, grey matter, white matter, grey matter in the hippocampus, and hippocampus, but increased lateral-ventricle volume. Inflammation accounted for 9.1% and 10.0% in the association of SUA with stroke and lateral-ventricle volume., Conclusions: Lower SUA levels increased the risk of Parkinsonism, while both lower and higher SUA levels were positively associated with increased risk of stroke and dementia. Moreover, high SUA levels reduced brain structure volumes. Our findings suggest the association between SUA levels and brain-related disorders and highlight the importance of SUA management., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: To review the changes and survey on status quo of the surgical treatment for esophageal cancer in China. The differences in diagnosis and treatment for esophageal cancer among hospitals in different regions across China were also investigated., Methods: We sent questionnaires to 46 hospitals across China, investigating the volume of esophageal cancer surgeries, surgical procedures, and perioperative management under the guidance of esophageal surgery chiefs., Results: A total of 46 questionnaires were sent out and collected. The survey results showed that in the past 5 years, the volume of surgeries for esophageal cancer remained stable by 23.9% of those hospitals, increased by 30.4%, and decreased by 45.7%. Of those patients treated by surgery, 19.1% were in the early stages, and 80.9% were in locally advanced stages. In terms of surgical procedures, 73.4% of the patients were treated by minimally invasive surgery and 85.7% of esophageal substitutes were a gastric conduit, 93.1% of the substitutes were pulled to the neck through the esophageal bed. For the lymph node dissection, 78.5% of the patients had a complete two-field lymph node dissection including the para-recurrent laryngeal nerve lymph nodes. Of the patients with neoadjuvant therapy, 53.5% received chemotherapy or chemotherapy plus immunotherapy (47.0%), and 43.5% had chemoradiation., Conclusions: Currently, in China, minimally invasive surgery-oriented multimodality treatment, including complete two-field lymph node dissection, has become the standard approach for esophageal cancer management. Over the past decade, this standardized approach has significantly improved prognosis compared to previous decades., (© 2024 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Background and Aims: Hepatitis B virus (HBV) vaccination programs in Taiwan are one of the earliest programs in the world and have largely reduced the prevalence of HBV infection. We aimed to demonstrate the vaccination efficacy after 35 years and identify gaps toward HBV elimination., Methods: A total of 4717 individuals aged 1-60 years were recruited from four administrative regions based on the proportion of population distribution. Serum levels of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc) levels were assessed. HBV viral load, genotypes and HBsAg 'ɑ' determinant variants were evaluated if indicated., Results: After 35 years of vaccination, the overall seropositivity rates for HBsAg and anti-HBc in Taiwan were 4.05% and 21.3%, respectively. The vaccinated birth cohorts exhibited significantly lower seropositivity rates for both markers compared to the unvaccinated birth cohorts (HBsAg: 0.64% vs. 9.78%; anti-HBc: 2.1% vs. 53.55%, respectively; p < 0.0001). Maternal transmission was identified as the main route of HBV infection in breakthrough cases. Additionally, increased prevalences of genotype C and HBsAg escape mutants were observed., Conclusion: The 35-year universal HBV vaccination program effectively reduced the burden of HBV infection, but complete eradication of HBV infection has not yet been achieved. In addition to immunization, comprehensive screening and antiviral therapy for infected individuals, especially for pregnant women, are crucial strategies to eliminate HBV., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: EGFR-mutated NSCLC is characterized by an immunosuppressive microenvironment that confers limited clinical effectiveness to anti-PD-1 or PD-L1 antibodies. Despite the discouraging outcomes of immunotherapy, novel immune checkpoints are constantly emerging, among which the specific vulnerability for therapeutic intervention in the context of EGFR-mutated NSCLC remains unresolved., Methods: Data sets of patient- and cell line-levels were used for screening and mutual validation of association between EGFR mutation and a panel of immune checkpoint-related genes. Regulatory mechanism was elucidated through in vitro manipulation of EGFR signaling pathway and evaluated by immunoblot analysis, quantitative polymerase chain reaction, flow cytometry, immunofluorescence staining, and chromatin immunoprecipitation. In vivo investigation of different therapeutic strategies were conducted using both immunocompetent and immunodeficient mouse models., Results: Among all screened immune checkpoints, CD47 emerged as the candidate most relevant to EGFR activation. Mechanistically, EGFR mutation constitutively activated downstream ERK and AKT pathways to respectively up-regulate the transcriptional factors c-Myc and NF-κB, both of which structurally bound to the promotor region of CD47 and actively transcribed this "don't eat me" signal. Impaired macrophage phagocytosis was observed on introduction of EGFR-sensitizing mutations in NSCLC cell line models, whereas CD47 blockade restored the phagocytic capacity and augmented tumor cell killing in both in vitro and in vivo models. Remarkably, the combination of anti-CD47 antibody with EGFR tyrosine kinase inhibitor revealed an additive antitumor activity compared with monotherapy of either antitumor agent in both immunocompetent and adaptive immunity-deficient mouse models., Conclusions: EGFR-sensitizing mutation facilitates NSCLC's escape from innate immune attack through up-regulating CD47. Combination therapy incorporating CD47 blockade holds substantial promise for clinical translation in developing more effective therapeutic approaches against EGFR-mutant NSCLC., Competing Interests: Disclosure Dr. Wu is an employee of Shenzhen Engineering Center for Translational Medicine of Precision Cancer Immunodiagnosis and Therapy, YuceBio Technology Co., Ltd. The remaining authors declare no conflict of interest, (Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate whether Naoxueshu Oral Liquid (NXS) could promote hematoma absorption in post-craniotomy hematoma (PCH) patients., Methods: This is an open-label, multicenter, and randomized controlled trial conducted at 9 hospitals in China. Patients aged 18-80 years with post-craniotomy supratentorial hematoma volume ranging from 10 to 30 mL or post-craniotomy infratentorial hematoma volume less than 10 mL, or intraventricular hemorrhage following cranial surgery were enrolled. They were randomly assigned at a 1:1 ratio to the NXS (10 mL thrice daily for 15 days) or control groups using a randomization code table. Standard medical care was administered in both groups. The primary outcome was the percentage reduction in hematoma volume from day 1 to day 15. The secondary outcomes included the percentage reduction in hematoma volume from day 1 to day 7, the absolute reduction in hematoma volume from day 1 to day 7 and 15, and the change in neurological function from day 1 to day 7 and 15. The safety was closely monitored throughout the study. Moreover, subgroup analysis was performed based on age, gender, history of diabetes, and etiology of intracerebral hemorrhage (ICH)., Results: A total of 120 patients were enrolled and randomly assigned between March 30, 2018 and April 15, 2020. One patient was lost to follow-up in the control group. Finally, there were 119 patients (60 in the NXS group and 59 in the control group) included in the analysis. In the full analysis set (FAS) analysis, the NXS group had a greater percentage reduction in hematoma volume from day 1 to day 15 than the control group [median (Q1, Q3): 85% (71%, 97%) vs. 76% (53%, 93%), P&lt;0.05]. The secondary outcomes showed no statistical significance between two groups, either in FAS or per-protocol set (P&gt;0.05). Furthermore, no adverse events were reported during the study. In the FAS analysis, the NXS group exhibited a higher percentage reduction in hematoma volume on day 15 in the following subgroups: male patients, patients younger than 65 years, patients without diabetes, or those with initial cranial surgery due to ICH (all P&lt;0.05)., Conclusions: The administration of NXS demonstrated the potential to promote the percentage reduction in hematoma volume from day 1 to day 15. This intervention was found to be safe and feasible. The response to NXS may be influenced by patient characteristics. (Registration No. ChiCTR1800017981)., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Given the realities of global aging, maintaining Comprehensive Geriatric Assessment (CGA) abilities among clinical nurses is very important. Newer methods of continuing education are needed to engage nurses in CGA education. Using multimedia and game-based applications in CGA education (CGA APP) may be an effective method for continuing education., Objectives: To test the effectiveness of CGA APP in improving nurses' confidence in their abilities to perform geriatric care., Design: A randomized, controlled trial were adopted., Setting: An 1343-bed tertiary-care medical center in southern Taiwan., Participants: A total of 1250 nurses met inclusion criteria in 35 adult wards. We employed stratified sampling to recruit a total of 132 nurses proportional to the number of nurses in each ward, from January to March 2019., Methods: Based on the Octalysis gamification framework, the CGA APP was developed. Participants were randomly assigned to either an CGA APP or a control group, which received traditional classroom learning of the same content. The main outcome was improvement in confidence in geriatric care ability were measured before and end of the training session, and six months later., Results: There were no differences in baseline characteristics (except years of experience as a registered nurse), knowledge, attitudes or confidence of geriatric care between the two groups. Clinical nurses in the CGA APP group demonstrated significantly higher confidence in their geriatric care abilities than control group immediately after the intervention (75.85 ± 10.71 vs. 65.93 ± 8.49, p < 0.001) and six-months later (71.13 ± 9.69 vs. 63.57 ± 8.78, p < 0.001). After using GEE to control the confounding variable, the CGA APP group remained significantly higher confidence in their geriatric care abilities than control group., Conclusions: Use of multimedia game-based applications my better engage and teach practicing clinical than traditional learning methods. Our findings suggest that such interventions be further developed and tested for a larger variety of continuing education needs., Competing Interests: Declaration of competing interest All the authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aims: This study aims to explore blood glucose variations before and after short-term intensive exercise in the morning or afternoon of a day and the trend of blood glucose fluctuations during exercise in patients with T2DM (type 2 diabetes, T2DM)., Methods: Blood glucose variations of Fouty during morning exercise 8:00-12:00 hours and twenty during afternoon exercise 14:30-18:30 hours). Patients with T2DM discharged from the hospital were analyzed retrospectively, with the baseline data checked through the medical record system before intervention. We were asked to perform seven times of treadmill aerobic exercise, which lasted for 30 minutes with incremental intensity for each time, for two weeks under the supervision of the Continuous Glucose Monitor (CGM) and the heart rate armband. The exercise intensity has been adjusted by the clinicians and specialist nurses from the Department of Diabetes Mellitus according to the blood glucose levels and heart rate curves during exercise; data including the height, weight, body mass index (BMI), waist-to-hip ratio, fasting blood glucose, glycosylated hemoglobin, in-exercise CGM-measured blood glucose value/min, and after-exercise fingertip blood glucose value of patients with T2DM were collected after the intensive exercise (2 weeks). SPSS 22.0 and GraphPad Prism 7 were adopted for statistical analysis using the T-test and ANOVA., Result: No difference was observed in the baseline data between the morning and afternoon exercise groups before intervention; compared to the morning exercise group, the fasting C-peptide value (2.15±0.97 vs. 1.53±0.46) in the afternoon exercise group was higher than that in the morning exercise group, with a superior (p=0.029) effect after two weeks of intervention, exhibiting a significant difference in the results. According to the results of repeated variance ANOVA analysis, the time for the appearance of significant improvement in blood glucose in the afternoon exercise group was 5 minutes earlier (11th minute vs 1 minute)than that in the morning exercise group (15th minute vs 1 min); significant differences were observed in both time (p=0.048 vs p<0.01) between the two groups on exercise days, as revealed by the results of bivariate ANOVA; in comparison to the morning exercise group (7.42±1.68), there was a significant difference (p=0.049)in the mean blood glucose between the two groups 25 min after patients with T2DM in the afternoon exercise group (6.25±1.53) started to exercise; in addition, a significant statistical difference (p=0.021) was revealed in the CGM-measured hourly the mean blood glucose on exercise days between the morning(8.18±1.88) and afternoon exercise (6.75±1.40)groups at 4:00 pm in week one and two w., Conclusions: Glycaemic improvement in the short-term intensive afternoon exercise group may be superior to that of the morning exercise group, which may be related to greater fasting C-peptide secretion and longer effective exercise duration. The time to exercise is a factor affecting blood glucose variations during exercise. However, significant variations in the level of blood glucose during exercise must be further observed through exercise intervention over a more extended period., Competing Interests: Declaration of Competing Interest All authors disclosed no relevant relationships., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The purpose of this study was to investigate the mediating effect of social support on the relationship between social activity and depressive symptoms among older widows in Taiwan. A cross-sectional study was conducted that recruited 256 older widows in southern Taiwan. Data were collected on demographic characteristics, self-rated health, instrumental activities of daily living, social activity, social support, and depression. Multiple linear regressions performed examined whether social activities and social support were significantly associated with depressive symptoms and which types of social activity were significantly related to social support and depressive symptoms. Mediation analyses performed tested the mediation effect of social support between the number of different types of social activities performed (termed "number of activities" in this study) and depression. Overall, 17.2% of the participants reported having at least two depressive symptoms. The total effect of the number of activities on depressive symptoms was significant ( p < .001). The direct pathway from the number of activities to depressive symptoms remained significant ( p < .001), and the mediation pathway (from the number of activities to depressive symptoms through social support) was also significant (Bootstrap CI = -.072, -.003). These findings demonstrated that older widows had more social support when they participated in more social activities, which could then decrease depressive symptoms. In addition, informal community group activities and religious group activities were the most effective at increasing social support and reducing depressive symptoms among the older Taiwanese widows.

Medical advances prolonging life have led to more permanent pacemaker implants. When pacemaker implantation (PMI) is commonly caused by sick sinus syndrome or conduction disorders, predicting PMI is challenging, as patients often experience related symptoms. This study was designed to create a deep learning model (DLM) for predicting future PMI from ECG data and assess its ability to predict future cardiovascular events. In this study, a DLM was trained on a dataset of 158,471 ECGs from 42,903 academic medical center patients, with additional validation involving 25,640 medical center patients and 26,538 community hospital patients. Primary analysis focused on predicting PMI within 90 days, while all-cause mortality, cardiovascular disease (CVD) mortality, and the development of various cardiovascular conditions were addressed with secondary analysis. The study's raw ECG DLM achieved area under the curve (AUC) values of 0.870, 0.878, and 0.883 for PMI prediction within 30, 60, and 90 days, respectively, along with sensitivities exceeding 82.0% and specificities over 81.9% in the internal validation. Significant ECG features included the PR interval, corrected QT interval, heart rate, QRS duration, P-wave axis, T-wave axis, and QRS complex axis. The AI-predicted PMI group had higher risks of PMI after 90 days (hazard ratio [HR]: 7.49, 95% CI: 5.40-10.39), all-cause mortality (HR: 1.91, 95% CI: 1.74-2.10), CVD mortality (HR: 3.53, 95% CI: 2.73-4.57), and new-onset adverse cardiovascular events. External validation confirmed the model's accuracy. Through ECG analyses, our AI DLM can alert clinicians and patients to the possibility of future PMI and related mortality and cardiovascular risks, aiding in timely patient intervention., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Angiostrongyliasis is a zoonotic parasitic disease caused by the rat lungworm Angiostrongylus cantonensis. The intermediate hosts of A. cantonensis are gastropods, and snail species such as Pomacea canaliculata play a key role in the transmission of human angiostrongyliasis. Detecting A. cantonensis infection in snails is an important component of epidemiological surveillance and the control of angiostrongyliasis., Methods: In this study, a new method for diagnosing A. cantonensis infection in gastropods was developed by recovering larvae from the buccal cavity of three snail species. The entire buccal cavity of a snail was extracted, and the tissue was pressed between two microscope slides to observe whether A. cantonensis larvae were present. Our new method was compared with traditional pathogenic detection methods of lung microscopy, tissue homogenization, and artificial digestion. We artificially infected 160 P. canaliculata, 160 Cipangopaludina chinensis, and 160 Bellamya aeruginosa snails with A. cantonensis. Then, the four different detection methods were used to diagnose infection in each snail species at 7, 14, 21, and 28 days post exposure., Results: We found no significant difference in the percentages of infected P. canaliculata snails using the four methods to detect A. cantonensis larvae. The radula pressing method had a mean detection rate of 80%, while the lung microscopy (81.3%), tissue homogenization (83.8%), and artificial digestion (85%) methods had slightly greater detection rates. Similarly, the percentages of infected C. chinensis snails that were detected using the radula pressing (80%), tissue homogenization (82.1%), and artificial digestion (83.8%) methods were not significantly different. Finally, the percentages of infected B. aeruginosa snails that were detected using the radula pressing (81.3%), tissue homogenization (81.9%), and artificial digestion (81.4%) methods were not significantly different. These results showed that the radula pressing method had a similar detection rate to traditional lung microscopy, tissue homogenization, or artificial digestion methods., Conclusions: This study demonstrates a new method for the qualitative screening of gastropods that act as intermediate hosts of A. cantonensis (and other Angiostrongylus species), provides technical support for the control of human angiostrongyliasis, and furthers research on A. cantonensis., (© 2024. The Author(s).)

The issues of state estimations based on distributed observers for linear time-invariant (LTI) systems with multiple sensors are discussed in this paper. We deal with the scenario when the information exchange has known time delays, and aim at designing a distributed observer for each subsystem such that each distributed observer can estimate the system state asymptotically by rejecting the time delay. To begin with, by rewriting the target system in a connecting form, a subsystem which is affected by the time-delay states of other nodes is established. And then, for this subsystem, a distributed observer with time delay is constructed. Moreover, an equivalent state transformation is made for the observer error dynamic system based on the observable canonic decomposition theorem. Further, in order to ensure that the distributed observer error dynamic system is asymptotically stable even if there exists a time delay, a linear matrix inequality (LMI) which is relative to the Laplace matrix is elaborately set up, and a special Lyapunov function candidate based on the LMI is considered. Next, based on the Lyapunov function and Lyapunov stability theory, we prove that the error dynamic system of the distributed observer is asymptotically stable, and the observer gain is determined by a feasible solution of the LMI. Finally, a simulation example is given to illustrate the effectiveness of the proposed method.

Background: The burden of asymptomatic left ventricular dysfunction (LVD) is greater than that of heart failure; however, a cost-effective tool for asymptomatic LVD screening has not been well validated. We aimed to prospectively validate an artificial intelligence (AI)-enabled electrocardiography (ECG) algorithm for asymptomatic LVD detection and evaluate its cost-effectiveness for opportunistic screening., Methods: In this prospective observational study, patients undergoing ECG at outpatient clinics or health check-ups were enrolled in 2 hospitals in Taiwan. Patients were stratified into LVD (left ventricular ejection fraction ≤ 40%) risk groups according to a previously developed ECG algorithm. The performance of AI-ECG was used to conduct a cost-effectiveness analysis of LVD screening compared with no screening. Incremental cost-effectiveness ratio (ICER) and sensitivity analyses were used to examine the cost-effectiveness and robustness of the results., Results: Among the 29,137 patients, the algorithm demonstrated areas under the receiver operating characteristic curves of 0.984 and 0.945 for detecting LVD within 28 days in the 2 hospital cohorts. For patients not initially scheduled for ECG, the algorithm predicted future echocardiograms (high-risk, 46.2%; medium-risk, 31.4%; low-risk, 14.6%) and LVD (high-risk, 26.2%; medium-risk, 3.4%; low-risk, 0.1%) at 12 months. Opportunistic screening with AI-ECG could result in a negative ICER of -$7,439 for patients aged 65 years, with consistent cost-savings across age groups and particularly in men. Approximately 91.5% of the cases were found to be cost-effective at the willingness-to-pay threshold of $30,000 in the probabilistic analysis., Conclusions: The use of AI-ECG for asymptomatic LVD risk stratification is promising, and opportunistic screening in outpatient clinics has the potential to reduce costs., (Copyright © 2023 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

The 16-item Physical Resilience Instrument for Older Adults (PRIFOR) has good clinimetric properties; however, a shortened PRIFOR would greatly enhance physical resilience measurements in clinical settings. The current analysis aimed to reduce the number of PRIFOR while maintaining its clinimetric properties, emphasizing on its factor structure and convergent validity. A longitudinal study was conducted among 863 patients aged 65 years or older. Four PRIFOR items with high factor loadings were selected to generate the short version of PRIFOR (PRIFOR-4). The PRIFOR-4 was found to have a unidimensional structure (comparative fit index = 0.999; Tucker-Lewis index = 0.998 in the confirmatory factor analysis results) with good convergent validity with various external measures (absolute r = 0.109-0.597; p-values<0.01). Because the PRIFOR-4 contains only four items, the completion time for the respondents reduced three fourths from the original PRIFOR, which may have a marked reduction in the response burden. The PRIFOR-4 is thus an easy-to-use measurement that saves time for healthcare professionals in clinical practice., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Devising carbon dots with long wavelength emission (red light or near infrared), high selectivity and good bio-compatibility is critical in fluorescence detection and imaging, but achieving this goal remains a great challenge. Herein, near-infrared emissive carbon dots (NIR-CDs) with obvious emission characteristic of 653 nm were synthesized through hydrothermally treatment of toluidine bule and gallic acid. Noticeably, the NIR-CDs exhibited excellent selectivity and sensitivity to hypochlorite (ClO - ), and the limit of detection is as low as 42.7 nM. The selective recognition reaction between ClO - and the surface functional groups of NIR-CDs inhibits the fluorescence from NIR-CDs. The quenching mechanism was confirmed by fluorescence lifetime decays, FT-IR spectroscopy and UV-vis absorption spectra. More remarkably, the NIR-CDs have rich hydrophilic groups showed lower cytotoxicity, excellent bio-compatibility and specific cell membrane localization ability. The established spectrofluorometric method based on NIR-CDs has been used to determination of ClO - level in tap water sample, the recoveries were 97.7 %-103.3 %. In addition, the NIR-CDs also has been successfully applied for the imaging of cell membrane. The study provides a novel idea for developing NIR ClO - probe as well as cell membrane localization probe based on CDs, which present bright prospects in real water samples monitoring and cell membrane imaging., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The treatment of acute respiratory distress syndrome (ARDS) complicated by sepsis syndrome (SS) remains challenging., Aim: To investigate whether combined adipose-derived mesenchymal-stem-cells (ADMSCs)-derived exosome (EX AD ) and exogenous mitochondria (mito Ex ) protect the lung from ARDS complicated by SS., Methods: In vitro study, including L2 cells treated with lipopolysaccharide (LPS) and in vivo study including male-adult-SD rats categorized into groups 1 (sham-operated-control), 2 (ARDS-SS), 3 (ARDS-SS + EX AD ), 4 (ARDS-SS + mito Ex ), and 5 (ARDS-SS + EX AD + mito Ex ), were included in the present study., Results: In vitro study showed an abundance of mito Ex found in recipient-L2 cells, resulting in significantly higher mitochondrial-cytochrome-C, adenosine triphosphate and relative mitochondrial DNA levels ( P < 0.001). The protein levels of inflammation [interleukin (IL)-1β/tumor necrosis factor (TNF)-α/nuclear factor-κB/toll-like receptor (TLR)-4/matrix-metalloproteinase (MMP)-9/oxidative-stress (NOX-1/NOX-2)/apoptosis (cleaved-caspase3/cleaved-poly (ADP-ribose) polymerase)] were significantly attenuated in lipopolysaccharide (LPS)-treated L2 cells with EX AD treatment than without EX AD treatment, whereas the protein expressions of cellular junctions [occluding/β-catenin/zonula occludens (ZO)-1/E-cadherin] exhibited an opposite pattern of inflammation (all P < 0.001). Animals were euthanized by 72 h post-48 h-ARDS induction, and lung tissues were harvested. By 72 h, flow cytometric analysis of bronchoalveolar lavage fluid demonstrated that the levels of inflammatory cells (Ly6G+/CD14+/CD68+/CD11 b/c +/myeloperoxidase+) and albumin were lowest in group 1, highest in group 2, and significantly higher in groups 3 and 4 than in group 5 (all P < 0.0001), whereas arterial oxygen-saturation (SaO 2 %) displayed an opposite pattern of albumin among the groups. Histopathological findings of lung injury/fibrosis area and inflammatory/DNA-damaged markers (CD68+/γ-H2AX) displayed an identical pattern of SaO 2 % among the groups (all P < 0.0001). The protein expressions of inflammatory (TLR-4/MMP-9/IL-1β/TNF-α)/oxidative stress (NOX-1/NOX-2/p22phox/oxidized protein)/mitochondrial-damaged (cytosolic-cytochrome-C/dynamin-related protein 1)/autophagic (beclin-1/Atg-5/ratio of LC3B-II/LC3B-I) biomarkers exhibited a similar manner, whereas antioxidants [nuclear respiratory factor (Nrf)-1/Nrf-2]/cellular junctions (ZO-1/E-cadherin)/mitochondrial electron transport chain (complex I-V) exhibited an opposite manner of albumin among the groups (all P < 0.0001)., Conclusion: Combined EX AD -mito Ex therapy was better than merely one for protecting the lung against ARDS-SS induced injury., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

A series of TADF-active compounds: 0D chiral Ln-Ag(I) clusters L-/D-Ln 2 Ag 28 -0D (Ln=Eu/Gd) and 2D chiral Ln-Ag(I) cluster-based frameworks L-/D-Ln 2 Ag 28 -2D (Ln=Gd) has been synthesized. Atomic-level structural analysis showed that the chiral Ag(I) cluster units {Ag 14 S 12 } in L-/D-Ln 2 Ag 28 -0D and L-/D-Ln 2 Ag 28 -2D exhibited similar configurations, linked by varying numbers of [Ln(H 2 O) x ] 3+ (x=6 for 0D, x=3 for 2D) to form the final target compounds. Temperature-dependent emission spectra and decay lifetimes measurement demonstrated the presence of TADF in L-Ln 2 Ag 28 -0D (Ln=Eu/Gd) and L-Gd 2 Ag 28 -2D. Experimentally, the remarkable TADF properties primarily originated from {Ag 14 S 12 } moieties in these compounds. Notably, {Ag 14 S 12 } in L-Eu 2 Ag 28 -0D and L-Gd 2 Ag 28 -2D displayed higher promote fluorescence rate and shorter TADF decay times than L-Gd 2 Ag 28 -0D. Combined with theoretical calculations, it was determined that the TADF behaviors of {Ag 14 S 12 } cluster units were induced by 4 f perturbation of Ln 3+ ions. Specially, while maintaining ΔE(S 1 -T 1 ) small enough, it can significantly increase k(S 1 →S 0 ) and reduce TADF decay time by adjusting the type or number of Ln 3+ ions, thus achieving the purpose of improving TADF for cluster-based luminescent materials., (© 2024 Wiley-VCH GmbH.)

Industrial enterprises are major sources of contaminants, making their regulation vital for sustainable development. Tracking contaminant generation at the firm-level is challenging due to enterprise heterogeneity and the lack of a universal estimation method. This study addresses the issue by focusing on hazardous waste (HW), which is difficult to monitor automatically. We developed a data-driven methodology to predict HW generation using wastewater big data which is grounded in the availability of this data with widespread application of automatic sensors and the logical assumption that a correlation exists between wastewater and HW generation. We created a generic framework that used representative variables from diverse sectors, exploited a data-balance algorithm to address long-tail data distribution, and incorporated causal discovery to screen features and improve computation efficiency. Our method was tested on 1024 enterprises across 10 sectors in Jiangsu, China, demonstrating high fidelity (R² = 0.87) in predicting HW generation with 4,260,593 daily wastewater data., (© 2024. The Author(s).)

Background: Finding individuals with drug-resistant tuberculosis (DR-TB) is important to control the pandemic and improve patient clinical outcomes. To our knowledge, systematic reviews assessing the effectiveness, cost-effectiveness, acceptability, and feasibility of different DR-TB case-finding strategies to inform research, policy, and practice, have not been conducted and the scope of primary research is unknown., Objective: We therefore assessed the available literature on DR-TB case-finding strategies., Methods: We looked at systematic reviews, trials, qualitative studies, diagnostic test accuracy studies, and other primary research that sought to improve DR-TB case detection specifically. We excluded studies that included patients seeking care for tuberculosis (TB) symptoms, patients already diagnosed with TB, or were laboratory-based. We searched the academic databases of MEDLINE, Embase, The Cochrane Library, Africa-Wide Information, CINAHL (Cumulated Index to Nursing and Allied Health Literature), Epistemonikos, and PROSPERO (The International Prospective Register of Systematic Reviews) using no language or date restrictions. We screened titles, abstracts, and full-text articles in duplicate. Data extraction and analyses were carried out in Excel (Microsoft Corp)., Results: We screened 3646 titles and abstracts and 236 full-text articles. We identified 6 systematic reviews and 61 primary studies. Five reviews described the yield of contact investigation and focused on household contacts, airline contacts, comparison between drug-susceptible tuberculosis and DR-TB contacts, and concordance of DR-TB profiles between index cases and contacts. One review compared universal versus selective drug resistance testing. Primary studies described (1) 34 contact investigations, (2) 17 outbreak investigations, (3) 3 airline contact investigations, (4) 5 epidemiological analyses, (5) 1 public-private partnership program, and (6) an e-registry program. Primary studies were all descriptive and included cross-sectional and retrospective reviews of program data. No trials were identified. Data extraction from contact investigations was difficult due to incomplete reporting of relevant information., Conclusions: Existing descriptive reviews can be updated, but there is a dearth of knowledge on the effectiveness, cost-effectiveness, acceptability, and feasibility of DR-TB case-finding strategies to inform policy and practice. There is also a need for standardization of terminology, design, and reporting of DR-TB case-finding studies., (©Susanna S van Wyk, Marriott Nliwasa, Fang-Wen Lu, Chih-Chan Lan, James A Seddon, Graeme Hoddinott, Lario Viljoen, Gunar Günther, Nunurai Ruswa, N Sarita Shah, Mareli Claassens. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 26.06.2024.)

Background: As long-term, regular aesthetic botulinum neurotoxin A (BoNT-A) use becomes more commonplace, it is vital to understand real-world risk factors and impact of BoNT-A immunoresistance. The first Aesthetic Council on Ethical Use of Neurotoxin Delivery panel discussed issues relating to BoNT-A immunoresistance from the health care professionals' (HCPs') perspective. Understanding the implications of BoNT-A immunoresistance from the aesthetic patient's viewpoint allows HCPs to better support patients throughout their aesthetic treatment journey., Methods: A real-world consumer study surveyed 363 experienced aesthetic BoNT-A recipients across six Asia-Pacific territories. The survey mapped participants' BoNT-A aesthetic treatment journey and characterized awareness and attitudes relating to BoNT-A immunoresistance and treatment implications. At the second Aesthetic Council on Ethical use of Neurotoxin Delivery meeting, panelists discussed survey findings and developed consensus statements relating to the impact of BoNT-A immunoresistance on the aesthetic treatment journey., Results: Aesthetic BoNT-A patients' depth of knowledge about BoNT-A immunoresistance remains low, and risk/benefit communications need to be more lay-friendly. The initial consultation is the most important touchpoint for HCPs to raise awareness of BoNT-A immunoresistance as a potential side effect considering increased risk with repeated high-dose treatments. HCPs should be cognizant of differences across BoNT-A formulations due to the presence of certain excipients and pharmacologically unnecessary components that can increase immunogenicity. Standardized screening for clinical signs of secondary nonresponse and a framework for diagnosing and managing immunoresistance-related secondary nonresponse were proposed., Conclusion: These insights can help patients and HCPs make informed treatment decisions to achieve desired aesthetic outcomes while preserving future treatment options with BoNT-A., Competing Interests: Dr. Corduff serves as a clinical advisor and speaker for Merz Aesthetics. Dr. Park serves as a consultant of Merz Aesthetics. Dr. Ho served as an advisory board member and consultant for Merz Aesthetics. Prof. Martin serve(d) as an ad-hoc consultant and speaker for Merz. Dr. Tseng serve(d) as a speaker, trainer, and advisory board member for Merz Aesthetics, AbbVie, Bausch & Lomb, Cynosure, Galderma, and Solta. Dr. Vachiramon serves as a speaker for Merz Aesthetics, LG Chem, Leo Pharma, Beiersdorf, L’Oreal, and as an advisory board member for Merz Aesthetics, AbbVie, and L’Oreal. Dr. Yu serves as a key opinion leader for Merz Aesthetic Philippines. Dr. Dingley is/was a speaker and advisor for and has received funding from Merz Aesthetics, Galderma, and Allergan. All authors have received honoraria from Merz Aesthetics for their contributions during the ASCEND panel meeting and subsequent manuscript preparation. The other authors have no financial interest to declare., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Hydropower plays a pivotal role in low-carbon electricity generation, yet many projects are situated in regions facing heightened water scarcity risks. This research devised a plant-level Hydropower Water Scarcity Index (HWSI), derived from the ratio of water demand for electricity generation to basin-scale available runoff water. We assessed the water scarcity of 1736 hydropower plants in China for the baseline year 2018 and projected into the future from 2025 to 2060. The results indicate a notable increase in hydropower generation facing moderate to severe water scarcity (HWSI >0.05), rising from 10% in 2018 to 24-34% of the national total (430-630 TWh), with a projected peak in the 2030s-2040s under the most pessimistic scenarios. Hotspots of risk are situated in the southwest and northern regions, primarily driven by decreased river basin runoff and intensified sectoral water use, rather than by hydropower demand expansion. Comparative analysis of four adaptation strategies revealed that sectoral water savings and enhancing power generation efficiency are the most effective, potentially mitigating a high of 16% of hydropower risks in China. This study provides insights for formulating region-specific adaptation strategies and assessing energy-water security in the face of evolving environmental and societal challenges.

Fatty acid-binding protein 4 (FABP4), a fatty acid transporter that coordinates lipid metabolism, is reported to exert a tumorigenic role in certain cancers. We investigated the effects of FABP4 in the carcinogenesis of thyroid cancer. Bioinformatics data about FABP4 in thyroid cancer were collected from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Sixteen paired papillary thyroid cancer (PTC) tissues from Taipei Medical University (TMU) were gathered, and commercial thyroid cancer complementary (c)DNA and tissue arrays were purchased to measure FABP4 messenger (m)RNA and protein levels. By analyzing data from the GEO and TCGA, we showed that FABP4 mRNA was reduced in PTC and follicular thyroid carcinoma (FTC). In addition, a lower FABP4 mRNA level in PTC was associated with poor clinical parameters and outcomes in the TCGA database. Moreover, FABP4 transcripts and proteins were downregulated in PTC and FTC, and its mRNA expression was associated with PTC staging in clinical specimens. In the TCGA database and TMU cohort, FABP4 mRNA levels were associated with thyroglobulin (r = 0.511 and r = 0.656, respectively), thyroid peroxidase (r = 0.612 and r = 0.909, respectively), and sodium iodide symporter (r = 0.485 and r = 0.637, respectively) transcripts. In conclusion, FABP4 mRNA and protein levels were reduced in PTC and FTC, and may be used as a potential indicator for thyroid cancer evolution in clinical settings. Further, well-designed research to dissect the molecular mechanism of FABP4 in modulating thyroid carcinogenesis is needed., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Diabetic foot ulcers (DFU), as severe complications of diabetes mellitus (DM), significantly compromise patient health and carry risks of amputation and mortality., Aim: To offer new insights into the occurrence and development of DFU, focusing on the therapeutic mechanisms of X-Paste (XP) of wound healing in diabetic mice., Methods: Employing traditional Chinese medicine ointment preparation methods, XP combines various medicinal ingredients. High-performance liquid chromatography (HPLC) identified XP's main components. Using streptozotocin (STZ)-induced diabetic, we aimed to investigate whether XP participated in the process of diabetic wound healing. RNA-sequencing analyzed gene expression differences between XP-treated and control groups. Molecular docking clarified XP's treatment mechanisms for diabetic wound healing. Human umbilical vein endothelial cells (HUVECs) were used to investigate the effects of Andrographolide (Andro) on cell viability, reactive oxygen species generation, apoptosis, proliferation, and metastasis in vitro following exposure to high glucose (HG), while NF-E2-related factor-2 ( Nrf2 ) knockdown elucidated Andro's molecular mechanisms., Results: XP notably enhanced wound healing in mice, expediting the healing process. RNA-sequencing revealed Nrf2 upregulation in DM tissues following XP treatment. HPLC identified 21 primary XP components, with Andro exhibiting strong Nrf2 binding. Andro mitigated HG-induced HUVECs proliferation, metastasis, angiogenic injury, and inflammation inhibition. Andro alleviates HG-induced HUVECs damage through Nrf2 /HO-1 pathway activation, with Nrf2 knockdown reducing Andro's proliferative and endothelial protective effects., Conclusion: XP significantly promotes wound healing in STZ-induced diabetic models. As XP's key component, Andro activates the Nrf2 /HO-1 signaling pathway, enhancing cell proliferation, tubule formation, and inflammation reduction., Competing Interests: Conflict-of-interest statement: The authors have declared that no competing interest exists., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background Diagnosing osteoporosis is challenging due to its often asymptomatic presentation, which highlights the importance of providing screening for high-risk populations. Purpose To evaluate the effectiveness of dual-energy x-ray absorptiometry (DXA) screening in high-risk patients with osteoporosis identified by an artificial intelligence (AI) model using chest radiographs. Materials and Methods This randomized controlled trial conducted at an academic medical center included participants 40 years of age or older who had undergone chest radiography between January and December 2022 without a history of DXA examination. High-risk participants identified with the AI-enabled chest radiographs were randomly allocated to either a screening group, which was offered fully reimbursed DXA examinations between January and June 2023, or a control group, which received usual care, defined as DXA examination by a physician or patient on their own initiative without AI intervention. A logistic regression was used to test the difference in the primary outcome, new-onset osteoporosis, between the screening and control groups. Results Of the 40 658 enrolled participants, 4912 (12.1%) were identified by the AI model as high risk, with 2456 assigned to the screening group (mean age, 71.8 years ± 11.5 [SD]; 1909 female) and 2456 assigned to the control group (mean age, 72.1 years ± 11.8; 1872 female). A total of 315 of 2456 (12.8%) participants in the screening group underwent fully reimbursed DXA, and 237 of 315 (75.2%) were identified with new-onset osteoporosis. After including DXA results by means of usual care in both screening and control groups, the screening group exhibited higher rates of osteoporosis detection (272 of 2456 [11.1%] vs 27 of 2456 [1.1%]; odds ratio [OR], 11.2 [95% CI: 7.5, 16.7]; P < .001) compared with the control group. The ORs of osteoporosis diagnosis were increased in screening group participants who did not meet formalized criteria for DXA compared with those who did (OR, 23.2 [95% CI: 10.2, 53.1] vs OR, 8.0 [95% CI: 5.0, 12.6]; interactive P = .03). Conclusion Providing DXA screening to a high-risk group identified with AI-enabled chest radiographs can effectively diagnose more patients with osteoporosis. Clinical trial registration no. NCT05721157 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Smith and Rothenberg in this issue.

Background: Gallstone disease is a common health problem worldwide. The role of the gut microbiota in gallstone pathogenesis remains obscure. Our aim was to evaluate the association and crosstalk between gut microbiota, gut metabolomic, and metabolic parameters in cholesterol gallstone patients, pigmented gallstone patients, and controls., Methods: We collected stool samples from healthy individuals and patients with gallstones in our hospital from March 2019 to February 2021. 16s rRNA sequencing was performed, followed by differential abundance analyses. Measurement of bile acids and short-chain fatty acids was conducted via targeted metabolomics., Result: Thirty healthy individuals and 20 gallstone patients were recruited. The intergroup difference of microbial composition was significant between control and gallstone patients. The control group had more abundant Faecalibacterium , Prevotella 9 , and Bacteroides plebeius DSM 17135 . The cholesterol stones group had higher Desulfovibrionaceae and Bacteroides uniformis than the other two groups, while the pigment stone group had more abundant Escherichia-Shigella . In the analysis of metabolites, only n-butyric acid had a significantly higher concentration in the controls than in the gallstone group ( p < 0.01). The level of 3α-hydroxy-12 ketolithocholic acid, deoxycholic acid, and cholic acid showed no intergroup differences but was correlated to the serum cholesterol level and bacterial richness and evenness., Conclusion: Our study revealed the key taxa that can discriminate between individuals with or without gallstones. We also identified metabolites that are possibly associated with metabolic parameter and bacterial diversity. However, the correlation of the metabolites to certain clusters of bacteria should be analyzed in a larger cohort., Competing Interests: Conflicts of interest: Dr. Yi-Hsiang Huang and Dr. Ming Hou, editorial board members at Journal of the Chinese Medical Association, have no roles in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)

Aim: The serum creatinine/cystatin C ratio (CCR) or sarcopenia index is considered a useful marker of muscle mass. However, its usefulness in late-stage older adults remains unclear. We aimed to determine the usefulness of CCR as an indicator of sarcopenia in community-dwelling Japanese adults aged >75 years., Methods: Our study recruited participants aged 70, 80, and 90 ± 1 years during the baseline years, and included a 3-year follow-up in the Septuagenarians, Octogenarians, Nonagenarians, Investigation with Centenarians study. From 2015 to 2018, 955 participants were eligible: 367 in their 70s, 304 in their 80s, and 284 in their 90s. The diagnostic components of sarcopenia, including "low muscle mass, plus low muscle strength, and/or low physical performance," were evaluated using the bioelectrical impedance analysis-measured skeletal muscle mass index (SMI), handgrip strength, and short physical performance battery (SPPB) score, respectively, in accordance with the Asia Working Group for Sarcopenia 2019 criteria. Separate analyses were performed between each component and CCR, adjusting for sex, body mass index, and other blood biomarkers in each group., Results: The relationship between CCR and sarcopenia components was significant for handgrip strength (β = 0.21, 0.13, 0.19, and P < 0.0001, =0.0088, <0.0001, for the 70s, 80s, and 90s age groups, respectively); however, it was limited for SMI (β = 0.14; P = 0.0022, only for the 90s) and not significant for the SPPB score., Conclusion: CCR is a limited indicator of sarcopenia in late-stage older adults. Although its association with muscle strength was significant, its relationship with muscle mass and physical performance was less pronounced. Geriatr Gerontol Int 2024; 24: 529-536., (© 2024 The Authors. Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.)

Novel components in the noncanonical Hippo pathway that mediate the growth, metastasis, and drug resistance of breast cancer (BC) cells need to be identified. Here, we showed that expression of SAM and SH3 domain-containing protein 1 (SASH1) is negatively correlated with expression of mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) in a subpopulation of patients with luminal-subtype BC. Downregulated SASH1 and upregulated MAP4K4 synergistically regulated the proliferation, migration, and invasion of luminal-subtype BC cells. The expression of LATS2, SASH1, and YAP1 and the phosphorylation of YAP1 were negatively regulated by MAP4K4, and LATS2 then phosphorylated SASH1 to form a novel MAP4K4-LATS2-SASH1-YAP1 cascade. Dephosphorylation of Yes1 associated transcriptional regulator (YAP1), YAP1/TAZ nuclear translocation, and downstream transcriptional regulation of YAP1 were promoted by the combined effects of ectopic MAP4K4 expression and SASH1 silencing. Targeted inhibition of MAP4K4 blocked proliferation, cell migration, and ER signaling both in vitro and in vivo. Our findings reveal a novel MAP4K4-LATS2-SASH1-YAP1 phosphorylation cascade, a noncanonical Hippo pathway that mediates ER signaling, tumorigenesis, and metastasis in breast cancer. Targeted intervention with this noncanonical Hippo pathway may constitute a novel alternative therapeutic approach for endocrine-resistant BC., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest related to the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Free radicals are increasingly recognized as active intermediate reactive species that can participate in various redox processes, significantly influencing the mechanistic pathways of reactions. Numerous researchers have investigated the generation of one or more distinct photogenerated radicals, proposing various hypotheses to explain the reaction mechanisms. Notably, recent research has demonstrated the emergence of photogenerated radicals in innovative processes, including organic chemical reactions and the photocatalytic dissolution of precious metals. To harness the potential of these free radicals more effectively, it is imperative to consolidate and analyze the processes and action modes of these photogenerated radicals. This conceptual paper delves into the latest advancements in understanding the mechanics of photogenerated radicals., (© 2024 Wiley-VCH GmbH.)

Background: Valvular heart disease (VHD) is becoming increasingly important to manage the risk of future complications. Electrocardiographic (ECG) changes may be related to multiple VHDs, and (AI)-enabled ECG has been able to detect some VHDs. We aimed to develop five deep learning models (DLMs) to identify aortic stenosis, aortic regurgitation, pulmonary regurgitation, tricuspid regurgitation, and mitral regurgitation., Methods: Between 2010 and 2021, 77,047 patients with echocardiography and 12-lead ECG performed within 7 days were identified from an academic medical center to provide DLM development (122,728 ECGs), and internal validation (7,637 ECGs). Additional 11,800 patients from a community hospital were identified to external validation. The ECGs were classified as with or without moderate-to-severe VHDs according to transthoracic echocardiography (TTE) records, and we also collected the other echocardiographic data and follow-up TTE records to identify new-onset valvular heart diseases., Results: AI-ECG adjusted for age and sex achieved areas under the curves (AUCs) of >0.84, >0.80, >0.77, >0.83, and >0.81 for detecting aortic stenosis, aortic regurgitation, pulmonary regurgitation, tricuspid regurgitation, and mitral regurgitation, respectively. Since predictions of each DLM shared similar components of ECG rhythms, the positive findings of each DLM were highly correlated with other valvular heart diseases. Of note, a total of 37.5-51.7% of false-positive predictions had at least one significant echocardiographic finding, which may lead to a significantly higher risk of future moderate-to-severe VHDs in patients with initially minimal-to-mild VHDs., Conclusion: AI-ECG may be used as a large-scale screening tool for detecting VHDs and a basis to undergo an echocardiography.

Introduction: Comprehensive geriatric assessment (CGA) is used to thoroughly assess and identify complex healthcare problems among older adults. However, administration of CGA is time-consuming and labor intensive. A simple screening tool with the mnemonic "FIND-NEEDS" was developed to quickly identify common geriatric conditions. The present study was to evaluate the clinimetric properties of the FIND-NEEDS., Methods: The participants comprised first-visiting older adults aged 65 years and above (and who were able to communicate by themselves or with the help of a caregiver) who were assessed (October to December, 2021) using the FIND-NEEDS and CGA at geriatric outpatient clinics of a tertiary, referred medical center. The FIND-NEEDS was examined for its criterion-related validity and compared with the CGA results. Two types of scoring (summed score and binary score) of FIND-NEEDS and CGA were analyzed using Spearman correlation, sensitivity and specificity, and area under receiver operating characteristic curve (AUC)., Results: The mean age of the 114 outpatients was 78.3 ± 7.6 years, and 79 (69.3%) were female. The internal consistency was excellent when using all FIND-NEEDS items, and was acceptable when using domain scores. Exploratory factor analysis showed that most of the FIND-NEEDS domain scores had factor loadings higher than 0.3. Intercorrelations of binary scores between domains of FIND-NEEDS and CGA showed most domains were moderately correlated. The overall correlation of summed scores between FIND-NEEDS and CGA was high. The FIND-NEEDS summed score was moderately correlated with CGA score (r = 0.494; p &lt; 0.001), and the binary score showed excellent correlation (r = 0.944; p &lt; 0.001). When using the CGA score as the gold standard, the FIND-NEEDS showed excellent AUC (0.950), sensitivity (1.00), and specificity (0.90)., Discussion/conclusion: The present study demonstrated that the FIND-NEEDS had acceptable clinimetric properties to screen for geriatric problems among older adults. Further in-depth assessment and care plan can then be conducted afterwards., (© 2024 S. Karger AG, Basel.)

The abnormal reproduction of algae in water worldwide is prominent in the context of human interference and global climate change. This study first thoroughly analyzed the effects of physical factors, such as light, temperature, hydrodynamics, and operational strategies, on algal growth and their mechanisms. Physical control techniques are safe and have great potential for preventing abnormal algal blooms in the absence of chemical reagents. The focus was on the principles and possible engineering applications of physical shading, ultrasound, micro-current, and ultraviolet (UV) technologies, in controlling abnormal algal reproduction. Physical shading can inhibit or weaken photosynthesis in algae, thereby inhibiting their growth. Ultrasound mainly affects the physiological and biochemical activities of cells by destroying the cell walls, air cells, and active enzymes. Micro-currents destroy the algal cell structure through direct and indirect oxidation, leading to algal cell death. UV irradiation can damage DNA, causing organisms to be unable to reproduce or algal cells to die directly. This article comprehensively summarizes and analyzes the advantages of physical prevention and control technologies for the abnormal reproduction of algae, providing a scientific basis for future research. In the future, attempts will be made toward appropriately and comprehensively utilizing various physical technologies to control algal blooms. The establishment of an intelligent, comprehensive physical prevention and control system to achieve environmentally friendly, economical, and effective physical prevention and control of algae, such as the South-to-North Water Diversion Project in China, is of great importance for specific waters., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Background: Recent evidence has demonstrated that abnormal expression and regulation of circular RNA (circRNAs) are involved in the occurrence and development of a variety of tumors. The aim of this study was to investigate the effects of circ&#95;PPAPDC1A in Osimertinib resistance in NSCLC., Methods: Human circRNAs microarray analysis was conducted to identify differentially expressed (DE) circRNAs in Osimertinib-acquired resistance tissues of NSCLC. The effect of circ&#95;PPAPDC1A on cell proliferation, invasion, migration, and apoptosis was assessed in both in vitro and in vivo. Dual-luciferase reporter assay, RT-qPCR, Western-blot, and rescue assay were employed to confirm the interaction between circ&#95;PPAPDC1A/miR-30a-3p/IGF1R axis., Results: The results revealed that circ&#95;PPAPDC1A was significantly upregulated in Osimertinib acquired resistance tissues of NSCLC. circ&#95;PPAPDC1A reduced the sensitivity of PC9 and HCC827 cells to Osimertinib and promoted cell proliferation, invasion, migration, while inhibiting apoptosis in Osimertinib-resistant PC9/OR and HCC829/OR cells, both in vitro and in vivo. Silencing circ&#95;PPAPDC1A partially reversed Osimertinib resistance. Additionally, circ&#95;PPAPDC1A acted as a competing endogenous RNA (ceRNA) by targeting miR-30a-3p, and Insulin-like Growth Factor 1 Receptor (IGF1R) was identified as a functional gene for miR-30a-3p in NSCLC. Furthermore, the results confirmed that circ&#95;PPAPDC1A/miR-30a-3p/IGF1R axis plays a role in activating the PI3K/AKT/mTOR signaling pathway in NSCLC with Osimertinib resistance., Conclusions: Therefore, for the first time we identified that circ&#95;PPAPDC1A was significantly upregulated and exerts an oncogenic role in NSCLC with Osimertinib resistance by sponging miR-30a-3p to active IGF1R/PI3K/AKT/mTOR pathway. circ&#95;PPAPDC1A may serve as a novel diagnostic biomarker and therapeutic target for NSCLC patients with Osimertinib resistance., (© 2024. The Author(s).)

The early identification of vulnerable patients has the potential to improve outcomes but poses a substantial challenge in clinical practice. This study evaluated the ability of an artificial intelligence (AI)-enabled electrocardiogram (ECG) to identify hospitalized patients with a high risk of mortality in a multisite randomized controlled trial involving 39 physicians and 15,965 patients. The AI-ECG alert intervention included an AI report and warning messages delivered to the physicians, flagging patients predicted to be at high risk of mortality. The trial met its primary outcome, finding that implementation of the AI-ECG alert was associated with a significant reduction in all-cause mortality within 90 days: 3.6% patients in the intervention group died within 90 days, compared to 4.3% in the control group (4.3%) (hazard ratio (HR) = 0.83, 95% confidence interval (CI) = 0.70-0.99). A prespecified analysis showed that reduction in all-cause mortality associated with the AI-ECG alert was observed primarily in patients with high-risk ECGs (HR = 0.69, 95% CI = 0.53-0.90). In analyses of secondary outcomes, patients in the intervention group with high-risk ECGs received increased levels of intensive care compared to the control group; for the high-risk ECG group of patients, implementation of the AI-ECG alert was associated with a significant reduction in the risk of cardiac death (0.2% in the intervention arm versus 2.4% in the control arm, HR = 0.07, 95% CI = 0.01-0.56). While the precise means by which implementation of the AI-ECG alert led to decreased mortality are to be fully elucidated, these results indicate that such implementation assists in the detection of high-risk patients, prompting timely clinical care and reducing mortality. ClinicalTrials.gov registration: NCT05118035 ., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Manure is one of the main sources of heavy metal (HM) pollution on farmlands. It has become the focus of global ecological research because of its potential threat to human health and the sustainability of food systems. Soil pH and organic matter are improved by manure and play pivotal roles in determining soil HM behavior. Geochemical modeling has been widely used to assess and predict the behavior of soil HMs; however, there remains a research gap in manure applications. In this study, a geochemical model (LeachXS) coupled with a pH-dependent leaching test with continuously simulations over a broad pH range was used to determine the effects and pollution risks of pig or cattle manure separate application on soil HMs distribution. Both pig and cattle manure applications led to soil pH reduction in alkaline soils and increased organic matter content. Pig manure application resulted in a potential 90.5-156.0 % increase in soil HM content. Cattle manure did not cause significant HM contamination. The leaching trend of soil HMs across treatments exhibited a V-shaped change, with the lowest concentration at pH = 7, gradually increasing toward strong acids and bases. The dissolved organic matter-bound HM content directly increased the HM availability, especially for Cu (up to 8.4 %) after pig manure application. However, more HMs (Cr, Cu, Zn, Ni) were in the particulate organic matter-bound state than in other solid phases (e.g., Fe-Al(hydr) oxides, clay minerals), which inhibited the HMs leaching by more than 19.3 % after cattle manure application. Despite these variations, high HM concentrations introduced by pig manure raised the soil contamination risk, potentially exceeding 40 times at pH ±1. When manure is returned to the field, reducing its HM content and mitigating possible pollution is necessary to realize the healthy and sustainable development of circular agriculture., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: This study aimed to investigate the mechanism of long noncoding ribonucleic acid (lncRNA) SNHG16 on kidney clear cell carcinoma (KIRC) cells by targeting miR-506-3p/ETS proto-oncogene 1, transcription factor (ETS1)/RAS/Extracellular regulated protein kinases (ERK) molecular axis, thus to provide reference for clinical diagnosis and treatment of KIRC in the future., Methods: Thirty-six patients with KIRC were enrolled in this study, and their carcinoma tissues and adjacent tissues were obtained for the detection of SNHG16/miR-506-3p/ETS1/RAS/ERK expression. Then, over-expressed SNHG16 plasmid and silenced plasmid were transfected into KIRC cells to observe the changes of their biological behavior., Results: SNHG16 and ETS1 were highly expressed while miR-506- 3p was low expressed in KIRC tissues; the RAS/ERK signaling pathway was significantly activated in KIRC tissues (P < 0.05). After SNHG16 silence, KIRC cells showed decreased proliferation, invasion and migration capabilities and increased apoptosis rate; correspondingly, increase in SNHG16 expression achieved opposite results (P < 0.05). Finally, in the rescue experiment, the effects of elevated SNHG16 on KIRC cells were reversed by simultaneous increase in miR-506-3p, and the effects of miR-506-3p were reversed by ETS1. Activation of the RAS/ERK pathway had the same effect as increase in ETS1, which further worsened the malignancy of KIRC. After miR-506-3p increase and ETS1 silence, the RAS/ERK signaling pathway was inhibited (P < 0.05). At last, the rescue experiment (co-transfection) confirmed that the effect of SNHG16 on KIRC cells is achieved via the miR-506-3p/ETS1/RAS/ERK molecular axis., Conclusion: SNHG16 regulates the biological behavior of KIRC cells by targeting the miR-506-3p/ETS1/RAS/ERK molecular axis., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Mingli Gu reports financial support was provided by Natural Science Key Project of Anhui Provincial Education Department. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Blood-brain barrier (BBB) disruption is increasingly recognized as an early contributor to the pathophysiology of cerebral ischemia/reperfusion (I/R) injury, and is also a key event in triggering secondary damage to the central nervous system. Recently, long non-coding RNA (lncRNA) have been found to be associated with ischemic stroke. However, the roles of lncRNA in BBB homeostasis remain largely unknown. Here, we report that long intergenic non-coding RNA-p21 (lincRNA-p21) was the most significantly down-regulated lncRNA in human brain microvascular endothelial cells (HBMECs) after oxygen and glucose deprivation/reoxygenation (OGD/R) treatment among candidate lncRNA, which were both sensitive to hypoxia and involved in atherosclerosis. Exogenous brain-endothelium-specific overexpression of lincRNA-p21 could alleviate BBB disruption, diminish infarction volume and attenuate motor function deficits in middle cerebral artery occlusion/reperfusion (MCAO/R) mice. Further results showed that lincRNA-p21 was critical to maintain BBB integrity by inhibiting the degradation of junction proteins under MCAO/R and OGD/R conditions. Specifically, lincRNA-p21 could inhibit autophagy-dependent degradation of occludin by activating PI3K/AKT/mTOR signaling pathway. Besides, lincRNA-p21 could inhibit VE-cadherin degradation by binding with miR-101-3p. Together, we identify that lincRNA-p21 is critical for BBB integrity maintenance, and endothelial lincRNA-p21 overexpression could alleviate cerebral I/R injury in mice, pointing to a potential strategy to treat cerebral I/R injury., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Phonon-based frequency combs that can be generated in the optical and microwave frequency domains have attracted much attention due to the small repetition rates and the simple setup. Here, we experimentally demonstrate a new type of phonon-based frequency comb in a silicon optomechanical crystal cavity including both a breathing mechanical mode (∼GHz) and flexural mechanical modes (tens of MHz). We observe strong mode competition between two approximate flexural mechanical modes, i.e., 77.19 and 90.17 MHz, resulting in only one preponderant lasing, while maintaining the lasing of the breathing mechanical mode. These simultaneous observations of two-mode phonon lasing state and significant mode competition are counterintuitive. We have formulated comprehensive theories to elucidate this phenomenon in response to this intriguing outcome. In particular, the self-pulse induced by the free carrier dispersion and thermo-optic effects interacts with two approximate flexural mechanical modes, resulting in the repetition rate of the comb frequency-locked to exact fractions of one of the flexural mechanical modes and the mode hopping between them. This phonon-based frequency comb has at least 260 comblines and a repetition rate as low as a simple fraction of the flexural mechanical frequency. Our demonstration offers an alternative optomechanical frequency comb for sensing, timing, and metrology applications.

Background: Mounting evidence has demonstrated that high temperature was associated with adverse health outcomes, especially morbidity and mortality. Nonetheless, the impact of extreme high temperature on cognitive performance, which is the fundamental capacity for interpreting one's surroundings, decision-making, and acquiring new abilities, has not been thoroughly investigated., Methods: We aimed to assess associations between extreme high temperature at different time scales and poor cognitive function. We used longitudinal survey data from the three waves of data from China Family Panel Study, providing an 8-year follow-up of 53,008 participants from China. We assessed temperature and extreme high temperature exposure for each participant based on the residential area and date of cognitive test. We defined the proportion of days/hours above 32 °C as the metric of the exposure to extreme high temperature. Then we used generalized additive model and difference-in-differences approach to explore the associations between extreme high temperature and cognitive function., Results: Our results demonstrated that either acute exposure or long-term exposure to extreme high temperature was associated with cognitive decline. At hourly level, 0-1 hour acute exposure to extreme high temperature would induce -0.93 % (95 % CI: -1.46 %, -0.39 %) cognitive change. At annual level, 10 percentage point increase in the hours proportion exceeding 32 °C in the past two years induced -9.87 % (95 % CI: -13.99 %, -5.75 %) cognitive change. Furthermore, subgroup analyses indicated adaptation effect: for the same 10 percentage increase in hours proportion exceeding 32 °C, people in warmer areas had cognitive change of -6.41 % (-11.22 %, -1.61 %), compared with -15.30 % (-21.07 %, -9.53 %) for people in cool areas., Conclusion: Our results demonstrated that extreme high temperature was associated with reduced cognitive function at hourly, daily and annual levels, warning that people should take better measures to protect the cognitive function in the context of climate change., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Nucleophilic substitutions are fundamentally important transformations in synthetic organic chemistry. Despite the substantial advances in bimolecular nucleophilic substitutions (S N 2) at saturated carbon centers, analogous S N 2 reaction at the amide nitrogen atom remains extremely limited. Here we report an S N 2 substitution method at the amide nitrogen atom with amine nucleophiles for nitrogen-nitrogen (N-N) bond formation that leads to a novel strategy toward biologically and medicinally important hydrazide derivatives. We found the use of sulfonate-leaving groups at the amide nitrogen atom played a pivotal role in the reaction. This new N-N coupling reaction allows the use of O-tosyl hydroxamates as electrophiles and readily available amines, including acyclic aliphatic amines and saturated N-heterocycles as nucleophiles. The reaction features mild conditions, broad substrate scope (>80 examples), excellent functional group tolerability, and scalability. The method is applicable to late-stage modification of various approved drug molecules, thus enabling complex hydrazide scaffold synthesis., (© 2024 Wiley‐VCH GmbH.)

Introduction: The literature on de novo EGFR T790M -mutant patients diagnosed with lung cancer is limited, and there is currently no consensus concerning the most effective treatment protocols. This study aimed to investigate the genomic characteristics of de novoEGFR T790M -mutant non-small cell lung cancer (NSCLC) and provide insights into its clinical response and resistance mechanism to third-generation EGFR-TKIs., Methods: Next-generation sequencing was utilized to screen a substantial cohort of 4,228 treatment-naïve patients from the Mygene genomic database to identifythe de novo EGFR-T790M mutation. Meanwhile, we recruited 83 individuals diagnosed with lung cancer who harbored de novo EGFR T790M mutation in the real world. In addition, 166 patients who acquired EGFR-T790M mutation after becoming resistant to first- or second-generation EGFR-TKIs were included as a comparison cohort., Results: De novo EGFR T790M mutation identified by next-generation sequencing is rare (∼1.3 %) in Chinese lung cancer patients. The relative variant allele frequency (VAF) of de novo EGFR T790M mutation was either comparable to or significantly lower than those of EGFR-activating mutations. Patients with de novo-T790M mutations exhibited less favorable clinical outcomes when administered third-generation EGFR-TKIs as first-line therapy thanthose with 19del mutationsdue to a high overlap rate in EGFR p.L858R mutation. In patients with a de novo EGFR T790M mutation, no correlation was observed between T790M clonality and treatment outcomes with third-generation EGFR-TKIs. In contrast, the sub-clonality of the T790M mutation detrimentally affected the third-generation EGFR-TKI treatment efficacy in patients with acquired T790M mutation. Potential resistance mechanisms of third-generation EGFR TKIs in NSCLC patients with de novo or acquired EGFR T790M mutations included EGFR p.C797S in cis or EGFR p.E709X mutation, as well as activation of bypass pathways., Conclusions: The present study characterized the uncommon but unique de novo EGFR T790M -mutant NSCLC and laid a foundation for designing future clinical trials in the setting of uncommon EGFR mutation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: Donor-derived infection (DDI) has become an important factor affecting the prognosis of lung transplantation patients. The risks versus benefits of using donor organs infected with multidrug-resistant organisms (MDRO), especially carbapenem-resistant organisms (CRO), are frequently debated. Traditional microbial culture and antimicrobial susceptibility testing at present fail to meet the needs of quick CRO determination for donor lungs before acquisition. In this study, we explored a novel screening method by using Xpert ® Carba-R assay for CRO in donor lungs in a real-time manner to reduce CRO-associated DDI mortality., Methods: This study was registered on chictr.org.cn (ChiCTR2100053687) on November 2021. In the Xpert Carba-R screening group, donor lungs were screened for CRO infection by the Xpert Carba-R test on bronchoalveolar fluid (BALF) before acquisition. If the result was negative, donor lung acquisition and subsequent lung transplantation were performed. In the thirty-five potential donors, nine (25.71%) with positive Xpert Carba-R results in BALF were declined for lung transplantation. Twenty-six recipients and the matching CRO-negative donor lungs (74.29%) were included in the Xpert Carba-R screening group. In the control group, nineteen recipients underwent lung transplants without Xpert Carba-R screening. The incidence and mortality of CRO-associated DDI were collected and contrasted between the two groups., Results: Multivariate analysis showed that CRO-related death due to DDI within 60 days was significantly lower in the Xpert Carba-R screening group than that in the control group (OR = 0.05, 95% CI 0.003-0.74, p = 0.03)., Conclusion: Real-time CRO screening of donor lungs before transplantation at the point of care by the Xpert Carba-R helps clinicians formulate lung transplantation strategies quickly and reduces the risk of subsequent CRO infection improving the prognosis of lung transplantation., (© 2023. The Author(s).)

In recent years, global warming has led to frequent instances of extremely high temperatures during summer, arousing significant concern about the adverse effects of high temperature. Among these, heat stroke is the most serious, which has detrimental effects on the all organs of human body, especially on brain. However, the comprehensive pathogenesis leading to brain damage remains unclear. In this study, we constructed a mouse model of heat stroke and conducted multi-omics profiling to identify relevant pathogenesis induced by heat stroke. The mice were placed in a constant temperature chamber at 42 °C with a humidity of 50 %, and the criteria for success in modeling were that the rectal temperature reached 42 °C and that the mice were trembling. Then the mice were immediately taken out for further experiments. Firstly, we conducted cFos protein localization and identified the cerebral cortex, especially the anterior cingulate cortex as the region exhibiting the most pronounced damage. Secondly, we performed metabolomics, transcriptomics, and proteomics analysis on cerebral cortex. This multi-omics investigation unveiled noteworthy alterations in proteins and metabolites within pathways associated with neurotransmitter systems, heatstroke-induced mitochondrial dysfunction, encompassing histidine and pentose phosphate metabolic pathways, as well as oxidative stress. In addition, the cerebral cortex exhibited pronounced Reactive Oxygen Species (ROS) production, alongside significant downregulation of the mitochondrial outer membrane protein Tomm40 and mitochondrial permeability transition pore, implicating cerebral cortex mitochondrial dysfunction as the primary instigator of neural impairment. This study marks a significant milestone as the first to employ multi-omics analysis in exploring the molecular mechanisms underlying heat stroke-induced damage in cerebral cortex neurons. It comprehensively identifies all potentially impacted pathways by heat stroke, laying a solid foundation for ensuing research endeavors. Consequently, this study introduces a fresh angle to clinical approaches in heatstroke prevention and treatment, as well as establishes an innovative groundwork for shaping future-forward environmental policies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Understanding the impact of heavy precipitation on human mobility is critical for finer-scale urban flood risk assessment and achieving sustainable development goals #11 to build resilient and safe cities. Using ∼2.6 million mobile phone signal data collected during the summer of 2018 in Jiangsu, China, this study proposes a novel framework to assess human mobility changes during rainfall events at a high spatial granularity (500 m grid cell). The fine-scale mobility map identifies spatial hotspots with abnormal clustering or reduced human activities. When aggregating to the prefecture-city level, results show that human mobility changes range between -3.6 and 8.9%, revealing varied intracity movement across cities. Piecewise structural equation modeling analysis further suggests that city size, transport system, and crowding level directly affect mobility responses, whereas economic conditions influence mobility through multiple indirect pathways. When overlaying a historical urban flood map, we find such human mobility changes help 23 cities reduce 2.6% flood risks covering 0.45 million people but increase a mean of 1.64% flood risks in 12 cities covering 0.21 million people. The findings help deepen our understanding of the mobility pattern of urban dwellers after heavy precipitation events and foster urban adaptation by supporting more efficient small-scale hazard management.

Aim: To examine the actual conditions of older patients receiving home medical care after hospitalization over a period of 2 years in Japan., Methods: The study population included 102 participants, aged ≥65 years, receiving home medical care, who consented to participate in the Osaka Home Care Registry (OHCARE) study in Japan over a period of 2 years. We investigated the actual conditions for returning home after hospitalization., Results: The median age of the 102 participants was 84 years, and 61 (59.8%) were women. In the group that returned home, 42 (55.3%) of the respondents desired to recuperate in a familiar place, as in advanced care planning (ACP). During the 2-year follow-up period, the group that did not return home had significantly more deaths. A multivariate analysis showed the association in the presence of ACP (odds ratio: 4.72, 95% confidence interval: 1.60-13.86) and cardiac disease (odds ratio: 0.25, 95% confidence interval: 0.08-0.76). The lack of ACP in the medical records when the patient was admitted to the hospital may have prevented the return home., Conclusion: In older patients who had difficulty returning home after hospitalization, the lack of ACP in home medical care may have been an influencing factor. ACP could help continue with home medical care. Geriatr Gerontol Int 2024; 24: 320-326., (© 2024 Japan Geriatrics Society.)

Background: Type 2 diabetes is often linked with osteoporosis (T2DOP), a condition that accelerates bone degeneration and increases the risk of fractures. Unlike conventional menopausal osteoporosis, the diabetic milieu exacerbates the likelihood of fractures and osteonecrosis. In particular poliumoside (Pol), derived from Callicarpa kwangtungensis Chun, has shown promising anti-oxidant and anti-inflammatory effects. Yet, its influence on T2DOP remains to be elucidated., Purpose: The focus of this study was to elucidate the influence of Pol in HGHF-associated ferroptosis and its implications in T2DOP., Study Design: A murine model of T2DOP was established using a minimal dosage of streptozotocin (STZ) through intraperitoneal infusion combined with a diet high in fat and sugar. Concurrently, to mimic the diabetic condition in a lab environment, bone mesenchymal stem cells (BMSCs) were maintained in a high-glucose and high-fat (HGHF) setting., Methods: The impact of Pol on BMSCs in an HGHF setting was determined using methods, such as BODIPY-C11, FerroOrange staining, mitochondrial functionality evaluations, and Western blot methodologies, coupled with immunoblotting and immunofluorescence techniques. To understand the role of Pol in a murine T2DOP model, techniques including micro-CT, hematoxylin and eosin (H&E) staining, dual-labeling with calcein-alizarin red, and immunohistochemistry were employed for detailed imaging and histological insights., Results: Our findings suggest that Pol acts against HGHF-induced bone degradation and ferroptosis, as evidenced by an elevation in glutathione (GSH) and a decline in malondialdehyde (MDA) levels, lipid peroxidation, and mitochondrial reactive oxygen species (ROS). Furthermore, Pol treatment led to increased bone density, enhanced GPX4 markers, and reduced ROS in the distal femur region. On investigating the underlying mechanism of action, it was observed that Pol triggers the Nrf2/GPX4 pathway, and the introduction of lentivirus-Nrf2 negates the beneficial effects of Pol in HGHF-treated BMSCs., Conclusion: Pol is effective in treating T2DOP by activating the Nrf2/GPX4 signaling pathway to inhibit ferroptosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)