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Fong-Yu Cheng,1 Yuan-Yow Chiou,2,3 Shih-Yuan Hung,4,5 Tsun-Mei Lin,6 Hao-Kuang Wang,7 Chi-Wei Lin,8 Hung-Hsiang Liou,9 Min-Yu Chang,5 Hsi-Hao Wang,5 Yi-Che Lee4,5,10 1Department of Chemistry, Chinese Culture University, Taipei, Taiwan; 2Department of Pediatrics, National Cheng Kung University Hospital, Tainan, Taiwan; 3Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 4School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan; 5Division of Nephrology, Department of Internal Medicine, E-DA Hospital, Kaohsiung, Taiwan; 6Department of Laboratory Medicine, E-DA Hospital, Kaohsiung, Taiwan; 7Department of Neurosurgery, E-DA Hospital, Kaohsiung, Taiwan; 8Department of Medical Education, E-DA Hospital, Kaohsiung, Taiwan; 9Division of Nephrology, Department of Internal Medicine, Hsin-Jen Hospital, New Taipei City, Taiwan; 10Division of Nephrology, Department of Internal Medicine, E-DA Dachang Hospital, Kaohsiung, TaiwanCorrespondence: Yi-Che LeeDivision of Nephrology, Department of Internal Medicine, E-DA Hospital/I-Shou University, No.1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City, 82445, Taiwan, R.O.CTel +886-7-6150011 Ext 5121Email pipijer@gmail.comPurpose: Vitamin D3 is useful for the treatment of peritoneal dialysis (PD)-related peritoneal damage, but its side effects, such as hypercalcemia and vascular calcification, limit its applicability. Thus, we developed vitamin D-loaded magnetic nanoparticles (MNPs) and determined their therapeutic efficacy and side effects in vivo.Materials and Methods: Alginate-modified MNPs were combined with 1α, 25 (OH)2D3 to generate vitamin D-loaded nanoparticles. The particles were conjugated with an antibody against peritoneum-glycoprotein M6A (GPM6A). The particles’ ability to target the peritoneum was examined following intraperitoneal administration to mice and by monitoring their bio-distribution. We also established a PD animal model to determine the therapeutic and side effects of vitamin D-loaded MNPs in vivo.Results: Vitamin D-loaded MNPs targeted the peritoneum better than vitamin D3, and had the same therapeutic effect as vitamin D3 in ameliorating peritoneal fibrosis and functional deterioration in a PD animal model. Most importantly, the particles reduced the side effects of vitamin D3, such as hypercalcemia and body weight loss, in mice.Conclusion: Vitamin D-loaded MNPs could be an ideal future therapeutic option to treat PD-related peritoneal damage.Keywords: peritoneal dialysis, nanoparticles, vitamin D, fibrosis

Yi-Che Lee,1–3 Chih-Ting Huang,4 Fong-Yu Cheng,5 Shih-Yuan Hung,3,6 Tsun-Mei Lin,7 Yen-Chang Tsai,4 Chih-I Chen,8 Hao-Kuang Wang,9 Chi-Wei Lin,10 Hung-Hsiang Liou,11 Min-Yu Chang,3 Hsi-Hao Wang,3 Yuan-Yow Chiou4,12 1Division of Nephrology, Department of Internal Medicine, E-DA Dachang Hospital/ I-Shou University, Kaohsiung, Taiwan; 2School of Medicine, College of Medicine; 3Division of Nephrology, Department of Internal Medicine, E-DA Hospital/ I-Shou University, Kaohsiung, Taiwan; 4Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 5Department of Chemistry, Chinese Culture University, Taipei, Taiwan; 6School of Medicine for International Students; 7Department of Laboratory Medicine; 8Division of Colorectal Surgery, Department of Surgery; 9Department of Neurosurgery; 10Department of Medical Education, E-DA Hospital/ I-Shou University, Kaohsiung, Taiwan; 11Division of Nephrology, Department of Medicine, Hsin-Jen Hospital, New Taipei City, Taiwan; 12Department of Pediatrics, National Cheng Kung University Hospital, Tainan, TaiwanCorrespondence: Yi-Che LeeDivision of Nephrology, Department of Internal Medicine, E-DA Hospital/I-Shou University, No.1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City 82445, Taiwan, ROCTel +886-7-6150011 ext. 5121Email pipijer@gmail.com Yuan-Yow ChiouInstitute of Clinical Medicine, Department of Pediatrics, National Cheng Kung University Hospital, Medical College, No. 138, Sheng-Li Road, Tainan City 701, Taiwan, ROCTel +886-6-2353535 ext. 4184Fax +886-6-2753083Email yuanyow@mail.ncku.edu.twPurpose: Vitamin D is a novel potential therapeutic agent for peritoneal dialysis (PD)-related peritoneal fibrosis, but it can induce hypercalcemia and vascular calcification, which limits its applicability. In this study, we create nanotechnology-based drug delivery systems to investigate its therapeutics and side effects.Materials and methods: 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N- [amino-(polyethylene glycol)2000] (DSPE-PEG) and L-α-phosphatidylcholine (PC), which packages with 1α,25(OH)2D3, were used to construct vitamin D nanoliposomes. To confirm the function and safety of vitamin D nanoliposomes, peritoneal mesothelial cells were treated with TGF-β1 and the reverse was attempted using vitamin D nanoliposomes. Antibodies (Ab) against the peritoneum-glycoprotein M6A (GPM6A) Ab were conjugated with vitamin D nanoliposomes. These particles were implanted into mice by intraperitoneal injection and the animals were monitored for the distribution and side effects induced by vitamin D.Results: Vitamin D nanoliposomes were taken up by the mesothelial cells over time without cell toxicity and it also provided the same therapeutic effect in vitro. In vivo study, fluorescent imaging showed vitamin D nanoliposomes allow specific peritoneum target effect and also ameliorate vitamin D side effect.Conclusion: Nanoliposomes vitamin D delivery systems for the prevention of PD-related peritoneal damage may be a potential clinical strategy in the future.Keywords: peritoneal dialysis, nanoliposome, vitamin D, fibrosis

Wen-Pin Su,1,2 Fong-Yu Cheng,3 Dar-Bin Shieh,3–6 Chen-Sheng Yeh,5–7 Wu-Chou Su1,2,81Graduate Institute of Clinical Medicine, College of Medicine, National Cheng Kung University; 2Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University; 3Institute of Oral Medicine, College of Medicine, National Cheng Kung University; 4Department of Stomatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University; 5Advanced Optoelectronic Technology Center; 6Center for Frontier Materials and Micro/Nano Science and Technology, and 7Department of Chemistry, National Cheng Kung University; 8Cancer Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.Abstract: Background: Effective cancer chemotherapy remains an important issue in cancer treatment, and signal transducer and activator of transcription-3 (Stat3) activation leads to cellular resistance of anticancer agents. Polymers are ideal vectors to carry both chemotherapeutics and small interfering ribonucleic acid (siRNA) to enhance antitumor efficacy. In this paper, poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with paclitaxel and Stat3 siRNA were successfully synthesized, and their applications in cancer cells were investigated.Methods: Firstly, paclitaxel was enclosed by PLGA nanoparticles through solvent evaporation. They were then coated with cationic polyethylenimine polymer (PLGA-PEI-TAX), enabling it to carry Stat3 siRNA on its surface through electrostatic interactions (PLGA-PEI-TAX-S3SI). The size, zeta potential, deliver efficacy, and release profile of the PLGA nanocomplexes were characterized in vitro. The cellular uptake, intracellular nanoparticle trajectory, and subsequent cellular events were evaluated after treatment with various PLGA nanocomplexes in human lung cancer A549 cells and A549-derived paclitaxel-resistant A549/T12 cell lines with α-tubulin mutation.Results: A549 and A549/T12 cells contain constitutively activated Stat3, and silencing Stat3 by siRNA made both cancer cells more sensitive to paclitaxel. Therefore, PLGA-PEI-TAX-S3SI was synthesized to test its therapeutic role in A549 and A549/T12 cells. Transmission electron microscopy showed the size of PLGA-PEI-TAX-S3SI to be around 250 nm. PLGA-PEI nanoparticles were nontoxic. PLGA-PEI-TAX was taken up by A549 and A549/T12 cells more than free paclitaxel, and they induced more condensed microtubule bundles and had higher cytotoxicity in these cancer cells. Moreover, the yellowish fluorescence observed in the cytoplasm of the cancer cells indicates that the PLGA-PEI nanoparticles were still simultaneously delivering Oregon Green paclitaxel and cyanine-5-labeled Stat3 siRNA 3 hours after treatment. Furthermore, after the cancer cells were incubated with the synthesized PLGA nanocomplexes, PLGA-PEI-TAX-S3SI suppressed Stat3 expression and induced more cellular apoptosis in A549 and A549/T12 cells compared with PLGA-PEI-TAX.Conclusion: The PLGA-PEI-TAX-S3SI complex provides a new therapeutic strategy to control cancer cell growth.Keywords: PLGA, nanoparticle, paclitaxel, siRNA, simultaneous drug delivery

Alzheimer's disease (AD, also known as dementia) has become a serious global health problem along with population aging, and neuroinflammation is the underlying cause of cognitive impairment in the brain. Nowadays, the development of multitarget anti-AD drugs is considered to be one effective approach. Imidazolylacetophenone oxime ethers or esters (IOEs) were multifunctional agents with neuroinflammation inhibition, metal chelation, antioxidant and neuroprotection properties against Alzheimer's disease. In this study, IOEs derivatives 1-8 were obtained by structural modifications of the oxime and imidazole groups, and the SARs showed that (Z)-oxime ether (derivative 2) had stronger anti-neuroinflammatory and neuroprotective ability than (E)-congener. Then, IOEs derivatives 9-30 were synthesized based on target-directed ligands and activity-based groups hybridization strategy. In vitro anti-AD activity screening revealed that some derivatives exhibited potentially multifunctional effects, among which derivative 28 exhibited the strongest inhibitory activity on NO production with EC 50 value of 0.49 μM, and had neuroprotective effects on 6-OHDA-induced cell damage and RSL3-induced ferroptosis. The anti-neuroinflammatory mechanism showed that 28 could inhibit the release of pro-inflammatory factors PGE 2 and TNF-α, down-regulate the expression of iNOS and COX-2 proteins, and promote the polarization of BV-2 cells from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype. In addition, 28 can dose-dependently inhibit acetylcholinesterase (AChE) and Aβ 42 aggregation. Moreover, the selected nuclide [ 18 F]-labeled 28 was synthesized to explore its biodistribution by micro-PET/CT, of which 28 can penetrate the blood-brain barrier (BBB). These results shed light on the potential of 28 as a new multifunctional candidate for AD treatment., 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 Masson SAS. All rights reserved.)

This study investigates the efficacy of ozone treatment combined with different packaging methods on the preservation of Taiwanese domestically produced beef during refrigerated storage. The preservation of fresh beef is crucial for ensuring food safety and quality; we do not know whether changing the packaging method can mitigate the negative effects of ozone on meat and even enhance its positive impact. Beef samples were treated with ozone and packaged using the vacuum or PVDC-tray methods, then stored at 4 °C for 7 days. The results show that ozone treatment effectively inhibited microbial (total plate count, Salmonella , and Escherichia coli ) growth ( p < 0.05). Vacuum packaging maintained lower TBARS values ( p < 0.05) and metmyoglobin percentages compared to PVDC-tray packaging ( p < 0.05). The L* values of all treatments increased over storage time, with significant differences observed between days 0 and 7. Ozone treatment combined with vacuum packaging demonstrated promising results in inhibiting microbial growth and preserving beef quality during refrigerated storage. These findings contribute to enhancing the safety and shelf life of Taiwanese domestically produced beef, potentially benefiting both producers and consumers.

Objective: This study evaluated the potential of Bacillus amyloliquefaciens to improve growth performance and meat quality in finishing pigs., Methods: Thirty-two female Landrace × Duroc pigs, 21 weeks old with initial body weight 77.45±3.29 kg, were divided into two groups: a control group (basal diet) and a probiotic group (basal diet with Bacillus amyloliquefaciens at 1×109 CFU/kg). Body weight and average daily gain (ADG) were recorded at the start and at fortnight intervals for a 56-d feeding trial. At the end of the experiment, carcass traits, meat quality and intramuscular fat related gene expression of longissimus dorsi muscle were analyzed., Results: The probiotic group showed significantly higher final body weight and D0-D56 ADG (p < 0.05). Additionally, the probiotic group had greater carcass weight, back fat thickness and marbling score (p < 0.05), while the lean meat percentage remained unchanged. Meat quality analysis revealed that the probiotic group had a higher b* value (5.47) (p < 0.05), and a lower shear value (p < 0.001), but there was no effect on the a* value and water holding capacity. Moreover, probiotic treatment increased the gene expression of fatty acid uptake and regulator, such as LPL, CD36, and SLC27A1 (p < 0.05)., Conclusion: Our findings suggest that the supplementation of Bacillus amyloliquefaciens not only enhanced growth performance and carcass weight in finishing pigs, but also improved marbling and tenderness in the longissimus dorsi muscle through the up-regulation of lipogenic-genes related to fat accumulation. This indicates its potential as feed additive to enhance pork quality.

This paper presents the efficacy of a contrast agent based on H 2 N-Fe 3 O 4 nanoparticles for the detection of prostate cancer in an animal model using a preclinical 9.4 T MRI system. The relaxivities r 1 and r 2 of the nanoparticles were 6.31 mM -1 s -1 and 8.33 mM -1 s -1 , respectively. Nanoparticles injected in a concentration of 2 mg Fe/mL decreased the tumor-relative T 1 relaxation across all animals from 100 to 76 ± 26, 85 ± 27, 89 ± 20, and 97 ± 16 12 min 1 h, 2 h, and 24 h post injection, respectively. The corresponding T 1 decrease in muscle tissues was 90 ± 20, 94 ± 23, 99 ± 12, and 99 ± 14. The relative T 2 changes in the tumor were 82 ± 17, 89 ± 19, 97 ± 14, and 99 ± 8 12 min, 1 h, 2 h, and 24 h post injection, respectively, while, for muscle tissues, these values were 95 ± 11, 95 ± 8, 97 ± 6, and 95 ± 10 at the corresponding time points. The differences in the relative T 1 and T 2 were only significant 12 min after injection ( p < 0.05), although a decrease was visible at each time point, but it was statistically insignificant ( p > 0.05). The results showed the potential application of H 2 N-Fe 3 O 4 nanoparticles as contrast agents for enhanced prostate cancer MRI.

Objective: To investigate fecal incontinence and defecatory, urinary, and sexual functional outcomes after transanal total mesorectal excision (taTME)., Background: Proctectomy for rectal cancer may result in alterations in defecatory, urinary, and sexual function that persist beyond 12 months. The recent multicenter phase II taTME trial demonstrated the safety of taTME in patients with stage I to III tumors., Methods: Prospectively registered self-reported questionnaires were collected from 100 taTME patients. Fecal continence [Fecal Incontinence Quality of Life (FIQL), Wexner], defecatory function [Colorectal Functional Outcome (COREFO)], urinary function (International Prostate Symptom Score), and sexual function (Female Sexual Function Index-female, International Index of Erectile Function-male) were assessed preoperatively (PQ), 3 to 4 months postileostomy closure (FQ1), and 12 to 18 months post-taTME [postoperative questionnaire 2 (FQ2)]., Results: Among 83 patients who responded at all 3 time points, FIQL, Wexner, and COREFO significantly worsened postileostomy closure. Between FQ1 and FQ2, FIQL lifestyle and coping, Wexner, and COREFO incontinence, social impact, frequency, and need for medication significantly improved, while FIQL depression and embarrassment did not change. International Prostate Symptom Score did not change relative to preoperative scores. For females, Female Sexual Function Index declined for desire, orgasm, and satisfaction between PQ and FQ1, and did not improve between FQ1 and FQ2. In males, International Index of Erectile Function declined with no change between FQ1 and FQ2., Conclusions: Although taTME resulted in initial decline in defecatory function and fecal continence, most functional domains improved by 12 months after ileostomy closure, without returning to preoperative status. Urinary function was preserved while sexual function declined without improvement by 18 months post-taTME. Our results address patient expectations and inform shared decision-making regarding taTME., Competing Interests: P.S.: consultant for Ethicon, Safeheal, Tissium, and Stryker. J.M.: consultant for Stryker, Intuitive, Medtronic; advisory board for Virtual Incision. J. Maykel: consultant for Olympus, Takeda, Safeheal, RedDress, Applied Medical. Karim Alavi: consultant for Safeheal and Olympus. K.Z.: consultant for Takeda, Intuitive, Natera. Sami Chadi: consultant for Stryker, Noah Medical. Alessio Pigazzi: Research grant from Vioptix; royalties with Xodus Medical; consultant for Medtronic and Ethicon. T.D.B.-A.: Honoraria for educational courses from Applied Medical. Matthew Albert: Research grants from Applied Medical, Stryker Endoscopy, Conmed, Human Extensions, Endoquest, Livsmed, Astellas Pharmaceuticals, Distal Motion, Proximie and Noah Medical; consultant for Applied Medical, Stryker, Distal Motion, EndoQuest, Astellas Pharmaceuticals, Livsmed and ConMed; Advisory board for Proximie and Distal Motion; stock options for Applied Medical, Proximie and Human Extensions. S.W.: Consultant for ARC/Corvus, Baxter, Becton Dickinson, GI Supply, Glaxo Smith Cline, ICON Clinical Research Limited, Intuitive Surgical, Leading BioSciences/Pallisade Bio, Livsmed, Medtronic, Olympus, Stryker, and Takeda; receives royalties from Intuitive Surgical, Karl Storz, Medtronic, Unique Surgical Innovations LLC. Stock options retained from prior consulting from CRH Medical and Intuitive Surgical. The remaining authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Under the background of comprehensively practicing the overall system concept of the "living community" in the new era, incorporating the carbon neutral development goal into the territorial spatial planning and construction and establishing the territorial spatial pattern and optimization strategy in line with the actual development of Gansu Province are of great significance for promoting the comprehensive green low-carbon transformation and high-quality development of regional economy and society. Taking counties in Gansu Province as an example, based on the perspective of carbon neutrality research, the land use carbon budget of 87 counties in Gansu Province in 2010, 2015, and 2021 was calculated and analyzed. GIS spatial analysis and social network analysis were used to further explore their spatial differentiation characteristics and the overall characteristics of the carbon emission spatial correlation network. At last, combined with the main function zoning, the low-carbon oriented land space optimization zoning was carried out, and differentiated low-carbon development strategies were proposed. The results were as follows： ① Carbon emissions in Gansu Province showed an upward trend, but the increase rate decreased, showing a spatial distribution of "high in the central and eastern part of the country, low in the southwest." Construction land was the main carbon source. The carbon uptake showed a spatial distribution of "high in the south and low in the north, high in the west and low in the east." Woodlands were the main carbon sinks. The net carbon emissions showed an increasing trend, and approximately 58.62% of the counties in the province were in a carbon imbalance situation. ② In 2021, the spatial network of county carbon emissions was closely related, showing a "core-edge" pattern. The Chenguan District and Qilihe District were in the core position of the network and received more correlation relationships in the network. The network contacts in Longzhong area were frequent, followed by the contacts in Longdongnan area. ③ Based on carbon emissions, carbon sequestration, and ecological carrying capacity coefficients and using the results of spatial correlation of social networks as role positions, the province was divided into four carbon-neutral sub-districts. At the same time, superimposed analysis of the main function zoning, the county area of the province was reconstructed into seven territorial space zones, and the differentiated regional low-carbon optimization development strategy was proposed for each zone.

Objectives: Machine learning algorithms can outperform older methods in predicting clinical deterioration, but rigorous prospective data on their real-world efficacy are limited. We hypothesized that real-time machine learning generated alerts sent directly to front-line providers would reduce escalations., Design: Single-center prospective pragmatic nonrandomized clustered clinical trial., Setting: Academic tertiary care medical center., Patients: Adult patients admitted to four medical-surgical units. Assignment to intervention or control arms was determined by initial unit admission., Interventions: Real-time alerts stratified according to predicted likelihood of deterioration sent either to the primary team or directly to the rapid response team (RRT). Clinical care and interventions were at the providers' discretion. For the control units, alerts were generated but not sent, and standard RRT activation criteria were used., Measurements and Main Results: The primary outcome was the rate of escalation per 1000 patient bed days. Secondary outcomes included the frequency of orders for fluids, medications, and diagnostic tests, and combined in-hospital and 30-day mortality. Propensity score modeling with stabilized inverse probability of treatment weight (IPTW) was used to account for differences between groups. Data from 2740 patients enrolled between July 2019 and March 2020 were analyzed (1488 intervention, 1252 control). Average age was 66.3 years and 1428 participants (52%) were female. The rate of escalation was 12.3 vs. 11.3 per 1000 patient bed days (difference, 1.0; 95% CI, -2.8 to 4.7) and IPTW adjusted incidence rate ratio 1.43 (95% CI, 1.16-1.78; p < 0.001). Patients in the intervention group were more likely to receive cardiovascular medication orders (16.1% vs. 11.3%; 4.7%; 95% CI, 2.1-7.4%) and IPTW adjusted relative risk (RR) (1.74; 95% CI, 1.39-2.18; p < 0.001). Combined in-hospital and 30-day-mortality was lower in the intervention group (7% vs. 9.3%; -2.4%; 95% CI, -4.5% to -0.2%) and IPTW adjusted RR (0.76; 95% CI, 0.58-0.99; p = 0.045)., Conclusions: Real-time machine learning alerts do not reduce the rate of escalation but may reduce mortality., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Cortical auditory evoked potentials (CAEPs) indicate that noise degrades auditory neural encoding, causing decreased peak amplitude and increased peak latency. Different types of noise affect CAEP responses, with greater informational masking causing additional degradation. In noisy conditions, attention can improve target signals' neural encoding, reflected by an increased CAEP amplitude, which may be facilitated through various inhibitory mechanisms at both pre-attentive and attentive levels. While previous research has mainly focused on inhibition effects during attentive auditory processing in noise, the impact of noise on the neural response during the pre-attentive phase remains unclear. Therefore, this preliminary study aimed to assess the auditory gating response, reflective of the sensory inhibitory stage, to repeated vowel pairs presented in background noise. CAEPs were recorded via high-density EEG in fifteen normal-hearing adults in quiet and noise conditions with low and high informational masking. The difference between the average CAEP peak amplitude evoked by each vowel in the pair was compared across conditions. Scalp maps were generated to observe general cortical inhibitory networks in each condition. Significant gating occurred in quiet, while noise conditions resulted in a significantly decreased gating response. The gating function was significantly degraded in noise with less informational masking content, coinciding with a reduced activation of inhibitory gating networks. These findings illustrate the adverse effect of noise on pre-attentive inhibition related to speech perception.

Background: Malnutrition is associated with increased morbidity, mortality, and healthcare costs. Early detection is important for timely intervention. This paper assesses the ability of a machine learning screening tool (MUST-Plus) implemented in registered dietitian (RD) workflow to identify malnourished patients early in the hospital stay and to improve the diagnosis and documentation rate of malnutrition., Methods: This retrospective cohort study was conducted in a large, urban health system in New York City comprising six hospitals serving a diverse patient population. The study included all patients aged ≥ 18 years, who were not admitted for COVID-19 and had a length of stay of ≤ 30 days., Results: Of the 7736 hospitalisations that met the inclusion criteria, 1947 (25.2%) were identified as being malnourished by MUST-Plus-assisted RD evaluations. The lag between admission and diagnosis improved with MUST-Plus implementation. The usability of the tool output by RDs exceeded 90%, showing good acceptance by users. When compared pre-/post-implementation, the rate of both diagnoses and documentation of malnutrition showed improvement., Conclusion: MUST-Plus, a machine learning-based screening tool, shows great promise as a malnutrition screening tool for hospitalised patients when used in conjunction with adequate RD staffing and training about the tool. It performed well across multiple measures and settings. Other health systems can use their electronic health record data to develop, test and implement similar machine learning-based processes to improve malnutrition screening and facilitate timely intervention., (© 2024 The British Dietetic Association Ltd.)

Background and Objectives: Pediatric fellows across all subspecialties are interested in global health (GH). Little is known about how GH is incorporated into Pediatric Hospital Medicine (PHM) fellowships. Our objective was to examine the current landscape of GH education in PHM fellowships., Methods: In 2022, we conducted a cross-sectional electronic survey of PHM fellowship directors (FDs), current fellows, and recently graduated fellows (alumni) via e-mail and listservs. Surveys asked about GH education (curriculum, electives, and research) in PHM fellowships, barriers to GH training, and fellow interest in GH., Results: Response rates were 56% (34/61) among PHM FDs, 57% (102/178) among fellows, and 29% (59/206) among alumni. Most fellows (73%) and alumni (59%) were interested in GH electives. Although 53% of FDs reported offering GH electives, a minority of fellows (21%) and alumni (19%) reported being offered GH electives (P <.001). Few FDs reported offering a GH curriculum (9%), although most fellows (63%) and alumni (50%) expressed interest. Of the 16 FDs without GH electives, 81% planned to offer them. Cited barriers included a lack of GH curricula, insufficient funding, competing educational demands, and a lack of international partnerships. More FDs (82%) than fellows (64%) and alumni (45%) agreed that GH education improves overall fellow education (P = .01). Similarly, more FDs (75%) than fellows (56%) and alumni (38%) agreed that offering GH education improves recruitment (P = .002)., Conclusions: There is an unmet demand for GH education in PHM fellowships, and fellows may not be aware of GH opportunities., (Copyright © 2024 by the American Academy of Pediatrics.)

1 H spin-lattice relaxation experiments have been performed for water and glycerol/water solutions of H 2 N-Fe 3 O 4 superparamagnetic nanoparticles (NPs) of about 7 nm diameter. The experiments encompass a broad frequency range covering 3 orders of magnitude, from 10 kHz to 10 MHz (referring to 1 H resonance frequency), and have been performed in the temperature range from 298 to 313 K, varying the concentration of the superparamagnetic species. This extensive dataset has been used for twofold purposes. The first one is to serve as a challenge for thorough tests of theoretical models describing nuclear relaxation in solutions of superparamagnetic NPs, depending on their magnetic properties and dynamics of the solvent molecules. The challenge is posed by the wish to reproduce the data in a broad range of magnetic fields (not only at high fields) and by the need to explain the differences in the relaxation scenarios for water and glycerol/water solutions by varying only the solvent parameters. The second purpose is to get insights into the magnetic properties (electronic relaxation properties) of the nanoparticles due to their high applicational potential.

Health education can elevate health literacy, which is associated with health knowledge, health-seeking behaviors and overall improved health outcomes. Refugees are particularly vulnerable to the effects of low health knowledge and literacy, which can exacerbate already poor health stemming from their displacement experience. Traditional learning methods including classroom-based instruction are typically how health-related information is presented to refugees. Through a series of interactive classes focused on specific health topics relevant to the resettled refugee population, this study evaluated the effectiveness of a classroom-based health education model in enhancing the health knowledge of recently resettled refugees. We used the Wilcoxon signed-rank test to evaluate differences in pre- and post-class knowledge through test performance. We found a significant improvement in health knowledge in two refugee groups: females and those who were employed. Culturally and socially sensitive considerations including language inclusiveness, class timing, transportation and childcare provisions are important when creating an educational program for individuals with refugee backgrounds. Developing focused approaches to instruction that enhance health knowledge could lead to better health literacy and ultimately improve health-related behaviors and outcomes in the refugee population., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Older adults with Mild Cognitive Impairment (MCI) are often subject to cognitive and gait deficits. Interactive Computerized Cognitive Training (ICCT) may improve cognitive function; however, the effect of such training on gait performance is limited. Transcranial Direct Current Stimulation (tDCS) improves cognition and gait performance. It remains unclear whether combining tDCS with ICCT produces an enhanced synergistic effect on cognition and complex gait performance relative to ICCT alone. This study aimed to compare the effects of tDCS combined with ICCT on cognition and gait performance in older adults with MCI., Method: Twenty-one older adults with MCI were randomly assigned to groups receiving either anodal tDCS and ICCT ( tDCS + ICCT ) or sham tDCS and ICCT ( sham + ICCT ). Participants played Nintendo Switch cognitive games for 40 min per session, simultaneously receiving either anodal or sham tDCS over the left dorsolateral prefrontal cortex for the first 20 min. Cognitive and gait assessments were performed before and after 15 training sessions., Results: The global cognition, executive function, and working-memory scores improved in both groups, but there were no significant interaction effects on cognitive outcomes. Additionally, the group × time interactions indicated that tDCS + ICCT significantly enhanced dual-task gait performance in terms of gait speed (p = 0.045), variability (p = 0.016), and dual-task cost (p = 0.039) compared to sham + ICCT., Conclusion: The combined effect of tDCS and ICCT on cognition was not superior to that of ICCT alone; however, it had a significant impact on dual-task gait performance. Administering tDCS as an adjunct to ICCT may thus provide additional benefits for older adults with MCI., Trial Registration: This trial was registered at http://www., Clinicaltrials: in.th/ (TCTR 20,220,328,009)., (© 2024. The Author(s).)

African swine fever (ASF) is a severe viral disease with a high mortality rate in domestic and wild pigs, for which no effective vaccine and antiviral drugs are available. The great infectivity of the ASF virus highlights the need for sensitive, simple, and on-site detection assays of ASF. We herein developed a colorimetric sensing strategy for the detection of an ASF-associated miRNA, based on isothermal rolling circle amplification (RCA) and salt-induced gold nanoparticle aggregation. Ssc-miR-451 was selected as the target ASF biomarker due to its high expression in ASF virus-infected pigs. With a red-purple-blue color shifting, this biosensing platform offers convenient detection of ssc-miR-451 with a UV-Vis spectrometer or the naked eye. The proposed assay exhibits a dose-response relationship between the optical absorbance ratio (A525/A640) and the amounts of ssc-miR-451, with a detection limit calculated as 3.56 fmol (equivalent to 11.86 pM in 300 μL reaction mixture). This assay's coefficient of variation (CV%) was determined to be less than 5.95%, revealing its reproducibility is satisfactory. In addition, the newly developed method was successfully applied in the detection of spiked ssc-miR-451 in pig serum samples. In light of its simplicity, convenience (colorimetric), sensitivity, and energy efficiency (isothermal amplification), this biosensing strategy presents great potential to be applied in the local swine industry and pig farming for screening of viral diseases affecting pigs., 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 © 2023. Published by Elsevier B.V.)

Abatement of volatile organic compounds (VOCs) ozone reduction is usually carried out by reducing the total amount of VOCs without considering reactivity between different species. This study incorporates the concept of maximum incremental reactivity (MIR) and speciation profiles into the industrial emission inventory of Taiwan to target organic species from industrial sources with the greatest ozone formation potentials (OFPs). These high OFP sources/species are then mitigated to assess the O 3 reduction amount (ΔO 3 ) with Community Multiscale Air Quality (CMAQ) modeling under VOC-limited conditions. The objective is to minimize the number of target sources/species and their tonnage while achieving maximum O 3 reduction. This approach is referred to as the Selective Precursor Mitigation (SPM). A case study of a high ozone episode (September 4-10, 2020) was chosen for illustration, during which a relatively stagnant atmospheric condition with minimal transboundary ozone occurred. A series of scenarios to target the highest OFP chemicals/industries for mitigation are compared for the achievable max. ΔO 3 , areas affected (area coverage), and reduction efficiency. For instance, by reducing the ten leading industry classes with the island's highest OFPs (OFP ind ), up to 19 % of max. 1-h ΔO 3 can be expected. If, however, the same tonnage of VOCs as that of OFP ind is distributed to all industries without considering the reactivity, called the overall mitigation (OM), comparable results to those of OFP ind were found, but the number of sources needed to be managed with OM would increase by nearly three times (29,662 for OM vs. 11,981 for OFP ind ). Further reducing the management scale by only zooming in the ten highest OFP chemicals within the ten leading OFP industries (OFP sp ) would result in relatively limited area coverage. Still, major ozone hot spots could be alleviated. Although the domain is set on the island of Taiwan, the SPM approach is universally applicable to other regions worldwide to gain the maximum ozone reduction effect at a minimized societal cost., 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 © 2023. Published by Elsevier B.V.)

Based on the background of carbon peaking and carbon neutrality goal strategies, it is important to explore the impact of land use change on carbon storage and the drivers of spatial variation in carbon storage in the Northwest Arid Zone, which is vital to improve the carbon sink increment of the regional ecosystem and promote the regional carbon breakeven. The arid region of northwest China is an extremely fragile natural ecology, and with the rapid advancement of new urbanization, the rate of land use change has accelerated significantly, which has a certain impact on the carbon storage and fixation capacity of ecosystems. The PLUS-InVEST model was used to simulate the spatial and temporal evolution characteristics of carbon storage under natural development, intensive development, water resource constraint, and ecological protection scenarios in Jiuquan City in 2035, and the parameter optimal geographic detector model was used to analyze the spatial divergence drivers of carbon storage. The results showed that:① the area of cultivated land, watershed, and construction land in Jiuquan City showed a significant increasing trend from 1990 to 2020, whereas the area of the remaining land use types showed a decreasing trend. ② The carbon storage in Jiuquan City increased from 7 722 808.1 t to 7 784 371 t from 1990 to 2020, and the conversion of grassland into unused land was the main cause of the loss of regional carbon storage, accounting for 85% of the total loss. ③ All four development scenarios in 2035 showed an increasing trend of carbon storage, among which the ecological protection scenario had the most significant increase, with an increment of 76 989.29 t. ④ The degree of land use, population density, GDP density, and NDVI were the main driving factors of the spatial variation in carbon storage in Jiuquan City, among which the degree of land use had the strongest explanatory power ( q value of 0.849), and the interaction of natural and anthropogenic factors enhanced the explanatory power of each factor on the spatial variation in carbon storage. The results of the study can provide a scientific basis and decision basis for the integrated ecosystem management and territorial space optimization in Jiuquan City.

Building a scientific and reasonable ecological network is the key for optimizing the pattern of territorial development and protection, and is of great significance for ensuring regional ecological security and promoting the virtuous cycle of ecosystems. In previous studies, nodal attack method (destruction of ecological source area) was often used in the "robustness" evaluation of ecological networks. Actually, the ecological corridor is more fragile than the source area, and thus the nodal attack method is not reasonable. In this study, taking Jiuquan City as the research area, based on the circuit model to construct the ecological network, we carried out the topology optimization of ecological network by using three strategies (random edge increase, node degree and priority edge increase with low node intermedium number) in complex network theory. We compared and analyzed the "robustness" of ecological network before and after optimization by constructing edge attack strategy, and selected the best network optimization strategy. The results showed that 65 ecological source areas were identified in Jiuquan City, with a total area of 20275.15 km 2 , and that grassland accounted for 89.5% of the source area. We identified 179 ecological corridors with a total length of 6387.16 km, 158 ecological barrier points with a total area of 1385.5 km 2 . The unused land accounted for 92.2% of the total barrier points area. We identified 63 ecological pinch points, mainly concentrated in the source edge and corridor intersection. Among them, the spatial distribution of 11 barrier points and pinch points was consistent, which was the key area to be repaired in ecological network optimization. The three optimization strategies had significantly improved the stability of ecological network in Jiuquan City. The relative size of the maximum connected subgraph and the edge connected rate of the ecological network of the optimization strategy of adding edges according to degree were all the most stable under random attack mode and deliberate attack mode, which was the best optimization scheme for ecological network in Jiuquan City.

The study aimed to investigate the PM 2.5 variations in different periods of COVID-19 control measures in Northern Taiwan from Quarter 1 (Q1) 2020 to Quarter 2 (Q2) 2021. PM 2.5 sources were classified based on long-range transport (LRT) or local pollution (LP) in three study periods: one China lockdown (P1), and two restrictions in Taiwan (P2 and P3). During P1 the average PM 2.5 concentrations from LRT (LRT-PM 2.5 - P1 ) were higher at Fuguei background station by 27.9% and in the range of 4.9-24.3% at other inland stations compared to before P1. The PM 2.5 from LRT/LP mix or pure LP (Mix/LP-PM 2.5 - P1 ) was also higher by 14.2-39.9%. This increase was due to higher secondary particle formation represented by the increase in secondary ions (SI) and organic matter in PM 2.5-P1 with the largest proportion of 42.17% in PM 2.5 from positive matrix factorization (PMF) analysis. A similar increasing trend of Mix/LP-PM 2.5 was found in P2 when China was still locked down and Taiwan was under an early control period but the rapidly increasing infected cases were confirmed. The shift of transportation patterns from public to private to avoid virus infection explicated the high correlation of the increasing infected cases with the increasing PM 2.5 . In contrast, the decreasing trend of LP-PM 2.5-P3 was observed in P3 with the PM 2.5 biases of ∼45% at all the stations when China was not locked down but Taiwan implemented a semi-lockdown. The contribution of gasoline vehicle sources in PM 2.5 was reduced from 20.3% before P3 to 10% in P3 by chemical signatures and source identification using PMF implying the strong impact of strict control measures on vehicle emissions. In summary, PM 2.5 concentrations in Northern Taiwan were either increased (P1 and P2) or decreased (P3) during the COVID-19 pandemic depending on control measures, source patterns and meteorological conditions., 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 © 2023 Elsevier Ltd. All rights reserved.)

Bimodal hearing, in which a contralateral hearing aid is combined with a cochlear implant (CI), provides greater speech recognition benefits than using a CI alone. Factors predicting individual bimodal patient success are not fully understood. Previous studies have shown that bimodal benefits may be driven by a patient's ability to extract fundamental frequency (f0) and/or temporal fine structure cues (e.g., F1). Both of these features may be represented in frequency following responses (FFR) to bimodal speech. Thus, the goals of this study were to: 1) parametrically examine neural encoding of f0 and F1 in simulated bimodal speech conditions; 2) examine objective discrimination of FFRs to bimodal speech conditions using machine learning; 3) explore whether FFRs are predictive of perceptual bimodal benefit. Three vowels (/ε/, /i/, and /ʊ/) with identical f0 were manipulated by a vocoder (right ear) and low-pass filters (left ear) to create five bimodal simulations for evoking FFRs: Vocoder-only, Vocoder +125 Hz, Vocoder +250 Hz, Vocoder +500 Hz, and Vocoder +750 Hz. Perceptual performance on the BKB-SIN test was also measured using the same five configurations. Results suggested that neural representation of f0 and F1 FFR components were enhanced with increasing acoustic bandwidth in the simulated "non-implanted" ear. As spectral differences between vowels emerged in the FFRs with increased acoustic bandwidth, FFRs were more accurately classified and discriminated using a machine learning algorithm. Enhancement of f0 and F1 neural encoding with increasing bandwidth were collectively predictive of perceptual bimodal benefit on a speech-in-noise task. Given these results, FFR may be a useful tool to objectively assess individual variability in bimodal hearing., (Copyright © 2023. Published by Elsevier B.V.)

Background: Mild cognitive impairment (MCI) is the stage between the expected cognitive decline of normal aging and the more serious decline of dementia. Previous studies have shown that regular exercise can improve cognition and physical performance in older adults. Walking is a low-technology and low-cost exercise that has been proven to improve cognition and mobility in healthy elderly individuals. However, no systematic review or meta-analysis has explored whether walking can improve cognitive function in older adults with MCI. This study aimed to explore the effects of walking interventions on cognitive functions in individuals with MCI., Methods: In accordance with the PRISMA guidelines, MEDLINE, PubMed, SPORTDiscus, Cochrane Central Register of Controlled Trials, CINAHL, Web of Science, Airiti Library, and the National Digital Library of Theses and Dissertations in Taiwan were searched from inception to July 2023. Independent reviewers selected randomized clinical trials (RCT) that compared the effects of walking with no intervention or other exercises in individuals with MCI. The primary outcomes were cognitive functions, and the secondary outcome was walking endurance. Three reviewers independently conducted data extraction. The risk of bias was assessed using the Revised Cochrane Risk of Bias assessment tool., Results: Fourteen RCTs were included in this review. The quality of evidence in these studies was rated as good to excellent. The results of the meta-analysis showed that the individuals with MCI had no significant improvement in cognitive function but had significant improvement in the 6-min walk test (Mean Difference=23.70, p=0.008) after walking interventions compared to no intervention or other exercises., Conclusion: Walking intervention has no significant improvement on cognitive functions in older adults with MCI. However, walking induces beneficial effects on aerobic capacity., Trial Registration: This systematic review has the registration number CRD42021283753 on PROSPERO., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Difficulties and anxiety caused by poor communication between patients with terminal cancer and their caregivers and medical teams are common in clinical practice. This may lead to uncertainty and fear of treatment, affecting the progress of treatment and achievement of hospice-care goals. The results of prior research indicate that using a question prompt list to promote shared decision-making can improve communication between medical care providers and patients., Purpose: This study was developed to explore the effectiveness of using question prompt lists in communications with terminal cancer patients and their families in clinical settings in Taiwan., Methods: A systematic review of the literature using a meta-analysis research design was conducted in this study. Cochrane Risk of Bias Tool 2 was used to assess literature quality. The selected keywords were used to search six databases, including the English-language PubMed, Cochrane Library, Embase, EBSCOhost, and MEDLINE databases and the Chinese-language Airiti Library database. RevMen 5.4 software (the latest version released by the Nordic Cochrane Center in September 2020) was used for data analysis., Results: Applying the question prompt list was found to significantly increase the number of questions asked (MD = 2.45, p = .01) and the usefulness (SMD = 0.25, p = .02). However, no significant changes in consultation time (MD = 4.49, p = .11), satisfaction (MD = 0.08, p = .91), or anxiety (SMD = 0.06, p = .62) were found., Conclusions / Implications for Practice: The results support that simplifying and focusing the topics of each chapter and theme of the question prompt list based on time of use may allow the list to be used effectively in combination with family meetings in clinical practice and to be focused based on patient, caregiver, and family needs to facilitate more-productive discussions. This will allow meetings to better facilitate therapeutic relationships and patient and caregiver participation in treatment plans. An external communication coach may be added in the future to help patients and caregivers clarify needs and concerns and improve the effectiveness of consultations. As questioning skills are important to empowering patients, a question prompt list for patients with terminal cancer should be developed. The results of this study may be used to guide the practice of healthcare providers and referenced in caregiver in-service education.

Chromosomes are a principal target of clinical cytogenetic studies. While chromosomal analysis is an integral part of prenatal care, the conventional manual identification of chromosomes in images is time-consuming and costly. This study developed a chromosome detector that uses deep learning and that achieved an accuracy of 98.88% in chromosomal identification. Specifically, we compiled and made available a large and publicly accessible database containing chromosome images and annotations for training chromosome detectors. The database contains five thousand 24 chromosome class annotations and 2,000 single chromosome annotations. This database also contains examples of chromosome variations. Our database provides a reference for researchers in this field and may help expedite the development of clinical applications., (© 2023. The Author(s).)

Objective: Chicken essence and branched chain amino acid (BCAA) supplementation has been recognized to significantly relieve fatigue. To obtain chicken essence with high amounts of BCAA, spent hens herein was used to prepare dripped chicken essence (SCE) and compared with commercial dripped chicken essence (CCE) for in vivo anti-fatigue effect., Methods: To determine the effect on anti-fatigue by dripped chicken essence, the exhaustive swimming was performed. Thirty-two 7-week ICR mice were divided into four groups, which included the control group (CG), CCE, SCE-1X and SCE-2X. The mice were given daily oral administration (0.012 mL/g body weight/d). The fatigue index analysis was conducted weekly., Results: The results showed that SCE had a higher BCAA level as expected, and mice treated with dripped chicken essence (CCE and SCE) could significantly improve exercise performance. The lower blood lactate level, blood urea nitrogen level and creatine phosphokinase activity were found in the supplement of SCE group compared with the CCE group, which suggested that the SCE possessed strong anti-fatigue ability. This could possibly be due to the higher content of BCAA., Conclusion: In this study, SCE promoted recovery from physical fatigue in mice and elevated endurance ability. Among them, the double dose (SCE-2X) showed the strongest anti-fatigue ability. Taken together, spent chickens could be a good source of chicken essence to improve the effect of anti-fatigue.

Background: Rapid antigen tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection have been authorized for emergency use (EUA); however, the performance has not been fully evaluated in clinical contexts. This study aimed to provide evidence regarding the diagnostic performance of SARS-CoV-2 rapid antigen tests compared with the real-time reverse transcription-polymerase chain reaction (RT-PCR) test in the emergency department (ED) and community., Methods: Patients who underwent SARS-CoV-2 rapid antigen tests using the VTRUST COVID-19 Antigen Rapid Test (TD-4531) and real-time RT-PCR on the same day in the ED or community from May 24, 2021, to June 24, 2021, were examined., Results: Paired nasopharyngeal swabs were collected from 4022 suspected COVID-19 patients: 800 in the ED and 3222 in the community. Overall, 62 (1.54%) tested positive, 13 tested indeterminate, and 3947 tested negative by real-time RT-PCR. The sensitivity and specificity of the antigen test were 51.61% and 99.44% (overall), 62.50% and 99.61% (ED), and 31.82% and 99.40% (community), respectively. There were 30 false negatives and 22 false positives. Among the false negatives, 16.67% had a cycle threshold (Ct) value of <25., Conclusion: The VTRUST COVID-19 Antigen Rapid Test showed comparable specificity as real-time RT-PCR for the ED and community, but the sensitivity was relatively low, especially when the Ct value was >25. This test can be useful for the rapid identification of infected subjects in an epidemic situation., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article., (Copyright © 2022 Pei-Chin Lin et al.)

Background: Motoric cognitive risk (MCR) syndrome is a conceptual construct that combines slow gait speed with subjective cognitive complaints and has been shown to be associated with an increased risk of developing dementia. However, the relationships between the pathology of Alzheimer's disease (AD) and MCR syndrome remain uncertain. Therefore, the purpose of this study was to determine the levels of plasma AD biomarkers (Aβ42 and total tau) and their relationships with cognition in individuals with MCR., Materials and Methods: This was a cross-sectional pilot study that enrolled 25 individuals with normal cognition (NC), 27 with MCR, and 16 with AD. Plasma Aβ42 and total tau (t-tau) levels were measured using immunomagnetic reduction (IMR) assays. A comprehensive neuropsychological assessment was also performed., Results: The levels of plasma t-tau proteins did not differ significantly between the MCR and AD groups, but that of plasma t-tau was significantly increased in the MCR and AD groups, compared to the NC group. Visuospatial performance was significantly lower in the MCR group than in the NC group. The levels of plasma t-tau correlated significantly with the Montreal Cognitive Assessment (MoCA) and Boston naming test scores in the MCR group., Conclusion: In this pilot study, we found significantly increased plasma t-tau proteins in the MCR and AD groups, compared with the NC group. The plasma t-tau levels were also significantly correlated with the cognitive function of older adults with MCR. These results implied that MCR and AD may share similar pathology. However, these findings need further confirmation in longitudinal studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Lin, Liao, Hsu and Cheng.)

Objective: We examined weight loss patterns and feeding practices of infants hospitalized for neonatal opioid withdrawal syndrome (NOWS) managed by the eat, sleep, console approach, which emphasizes nonpharmacologic treatment. Although feeding practices during hospitalization vary widely, weight loss patterns for infants managed under this approach have not yet been described., Methods: Of 744 infants with NOWS born from 2014 to 2019 at our institution, 330 met inclusion criteria (≥35 weeks' gestation and no NICU transfer). We examined maximum weight loss and created weight loss percentile curves by delivery type using mixed effects quantile modeling with spline effect for hour of life; 95% confidence intervals (CI) were compared to published early weight loss nomograms., Results: In the cohort, the mean gestational age was 39.2 weeks, mean birth weight was 3.1 kg, and mean length of stay was 6.5 days; 94.6% did not require pharmacologic treatment. Median percent weight loss was significantly more compared to early weight loss nomograms for both vaginally-delivered infants at 48 hours (6.9% [95% CI: 5.8-8.5] vs 2.9%) and cesarean-delivered infants at 48 hours (6.5% [95% CI: 4.1-9.1] vs 3.7%) and 72 hours (7.2% [95%CI 4.7-9.9] vs 3.5%), all P < .001. Overall, 27.9% lost >10% birth weight., Conclusions: We demonstrate weight loss patterns of infants with NOWS managed by the eat, sleep, console approach at a single center. Infants with NOWS lose significantly more weight than nonopioid exposed infants and are at increased risk of morbidity and health care use. Studies to address optimal feeding methods in these infants are warranted., (Copyright © 2022 by the American Academy of Pediatrics.)

Nanotechnology allows for a greater quality of life, but may also cause environmental and organismic harm. Zinc oxide nanoparticles (ZnONPs) are one of the most commonly used metal oxide nanoparticles for commercial and industrial products. Due to its extensive use in various fields, there has already been much concern raised about the environmental health risks of ZnONPs. Many studies have investigated the toxicological profile of ZnONPs in zebrafish embryonic development; however, the specific characteristics of ZnONPs in zebrafish embryonic/larval developmental damage and their molecular toxic mechanisms of liver development are yet to be fully elucidated. This study aimed to reveal the hazard ranking of different surface modifications of ZnONPs on developing zebrafish and the toxicological mechanisms of these modified ZnONPs in liver tissue. The ~30 nm ZnONPs with amino- (NH 2 - ZnONPs) or carboxyl- (COOH-ZnONPs) modification were incorporated during the embryonic/larval stage of zebrafish. Severe toxicity was observed in both ZnONP groups, especially NH 2 -ZnONPs, which presented a higher toxicity in the low concentration groups. After prolonging the exposure time, the long-term toxicity assay showed a greater retardation in body length of zebrafish in the NH 2 -ZnONP group. Response data from multiple toxicity studies was integrated for the calculation of the EC 50 values of bulk ZnO and ZnONPs, and the hazard levels were found to be decreasing in the order of NH 2 -, COOH-ZnONPs and bulk ZnO. Notably, NH 2 -ZnONPs induced ROS burden in the developing liver tissue, which activated autophagy-related gene and protein expression and finally induced liver cell apoptosis to reduce liver size. In conclusion, our findings are conducive to understanding the hazard risks of different surface modifications of ZnONPs in aquatic environments and will also be helpful for choosing the type of ZnONPs in future industrial applications., 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 © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

This study developed a predictive model for cognitive degeneration in patients with Parkinson's disease (PD) using a machine learning method. The clinical data, plasma biomarkers, and neuropsychological test results of patients with PD were collected and utilized as model predictors. Machine learning methods comprising support vector machines (SVMs) and principal component analysis (PCA) were applied to obtain a cognitive classification model. Using 32 comprehensive predictive parameters, the PCA-SVM classifier reached 92.3% accuracy and 0.929 area under the receiver operating characteristic curve (AUC). Furthermore, the accuracy could be increased to 100% and the AUC to 1.0 in a PCA-SVM model using only 13 carefully chosen features.

Cancer cells can acquire resistance to targeted therapeutic agents when the designated targets or their downstream signaling molecules develop protein conformational or activity changes. There is an increasing interest in developing poly‑pharmacologic anticancer agents to target multiple oncoproteins or signaling pathways in cancer cells. The microRNA 125a‑5p (miR‑125a‑5p) is a tumor suppressor, and its expression has frequently been downregulated in tumors. By contrast, the anti‑apoptotic molecule BIRC5/SURVIVIN is highly expressed in tumors but not in the differentiated normal tissues. In the present study, the development of a BIRC5 gene promoter‑driven, miR‑125a‑5p expressing, poly‑L‑lysine‑conjugated magnetite iron poly‑pharmacologic nanodrug (pL‑MNP‑pSur‑125a) was reported. The cancer cells self‑activating property and the anticancer effects of this nanodrug were examined in both the multidrug efflux protein ABCB1/MDR1‑expressing/‑non‑expressing cancer cells in vitro and in vivo . It was demonstrated that pL‑MNP‑pSur‑125a decreased the expression of ERBB2/HER2, HDAC5, BIRC5, and SP1, which are hot therapeutic targets for cancer in vitro . Notably, pL‑MNP‑pSur‑125a also downregulated the expression of TDO2 in the human KB cervical carcinoma cells. PL‑MNP‑pSur‑125a decreased the viability of various BIRC5 ‑expressing cancer cells, regardless of the tissue origin or the expression of ABCB1, but not of the human BIRC5 ‑non‑expressing HMEC‑1 endothelial cells. In vivo , pL‑MNP‑pSur‑125a exhibited potent antitumor growth effects, but without inducing liver toxicity, in various zebrafish human‑ABCB1‑expressing and ABCB1‑non‑expressing tumor xenograft models. In conclusion, pL‑MNP‑pSur‑125a is an easy‑to‑prepare and a promising poly‑pharmacological anticancer nanodrug that has the potential to manage numerous malignancies, particularly for patients with BIRC5/ABCB1‑related drug resistance after prolonged chemotherapeutic treatments.

Mild cognitive impairment (MCI) is considered an intermediate state between normal aging and early dementia. Fear of falling (FOF) could be considered a risk indicator for falls and quality of life in individuals with MCI. Our objective was to explore factors associated with FOF in those with MCI due to Alzheimer's disease (AD-MCI) and mild cognitive impairment in Parkinson's disease (PD-MCI). Seventy-one participants were separated into two groups, AD-MCI ( n = 37) and PD-MCI ( n = 34), based on the disease diagnosis. FOF was assessed using the Activities-specific Balance Confidence scale. The neuropsychological assessment and gait assessment were also measured. FOF was significantly correlated with global cognitive function, attention and working memory, executive function, Tinetti assessment scale scores, gait speed, and stride length in the AD-MCI group. Moreover, attention and working memory were the most important factors contributing to FOF. In the PD-MCI group, FOF was significantly correlated with gait speed, and time up and go subtask performance. Furthermore, turn-to-walk was the most important factor contributing to FOF. We noted that FOF in different types of MCI was determined by different factors. Therapies that aim to lower FOF in AD-MCI and PD-MCI populations may address attention and working memory and turn-to-walk, respectively.

Schizophrenia is a complex mental disorder with a genetic component. The GRIK gene family encodes ionotropic glutamate receptors of the kainate subtype, which are considered candidate genes for schizophrenia. We screened for rare and pathogenic mutations in the protein-coding sequences of the GRIK gene family in 516 unrelated patients with schizophrenia using the ion semiconductor sequencing method. We identified 44 protein-altered variants, and in silico analysis indicated that 36 of these mutations were rare and damaging or pathological based on putative protein function. Notably, we identified four truncating mutations, including two frameshift deletion mutations ( GRIK1 p.Phe24fs and GRIK1 p.Thr882fs ) and two nonsense mutations ( GRIK2 p.Arg300Ter and GRIK4 p.Gln342Ter ) in four unrelated patients with schizophrenia. They exhibited minor allele frequencies of less than 0.01% and were absent in 1517 healthy controls from Taiwan Biobank. Functional analysis identified these four truncating mutants as loss-of-function (LoF) mutants in HEK-293 cells. We also showed that three mutations ( GRIK1 p.Phe24fs , GRIK1 p.Thr882fs , and GRIK2 p.Arg300Ter ) weakened the interaction with the PSD95 protein. The results suggest that the GRIK gene family harbors ultrarare LoF mutations in some patients with schizophrenia. The identification of proteins that interact with the kainate receptors will be essential to determine kainate receptor-mediated signaling in the brain.

Arc/Arg3.1 (activity-regulated cytoskeletal-associated protein (ARC)) is a critical regulator of long-term synaptic plasticity and is involved in the pathophysiology of schizophrenia. The functions and mechanisms of human ARC action are poorly understood and worthy of further investigation. To investigate the function of the ARC gene in vitro, we generated an ARC -knockout (KO) HEK293 cell line via CRISPR/Cas9-mediated gene editing and conducted RNA sequencing and label-free LC-MS/MS analysis to identify the differentially expressed genes and proteins in isogenic ARC -KO HEK293 cells. Furthermore, we used bioluminescence resonance energy transfer (BRET) assays to detect interactions between the ARC protein and differentially expressed proteins. Genetic deletion of ARC disturbed multiple genes involved in the extracellular matrix and synaptic membrane. Seven proteins (HSPA1A, ENO1, VCP, HMGCS1, ALDH1B1, FSCN1, and HINT2) were found to be differentially expressed between ARC -KO cells and ARC wild-type cells. BRET assay results showed that ARC interacted with PSD95 and HSPA1A. Overall, we found that ARC regulates the differential expression of genes involved in the extracellular matrix, synaptic membrane, and heat shock protein family. The transcriptomic and proteomic profiles of ARC -KO HEK293 cells presented here provide new evidence for the mechanisms underlying the effects of ARC and molecular pathways involved in schizophrenia pathophysiology.

Background: Declined cognitive function interferes with dual-task walking ability and may result in falls in older adults with mild cognitive impairment (MCI). The mind-body exercise, Tai Chi (TC), improves cognition and dual-task ability. Exergaming is low-cost, safe, highly scalable, and feasible. Whether the effects of exergaming-based TC is beneficial than traditional TC has not been investigated yet., Objectives: The objective of this study was to investigate effects of exergaming-based TC on cognitive function and dual-task walking among older adults with MCI., Methods: Fifty patients with MCI were randomly assigned to an exergaming-based TC (EXER-TC) group, a traditional TC (TC) group, or a control group. The EXER-TC and TC groups received 36 training sessions (three, 50-min sessions per week) during a 12-week period. The control group received no intervention and were instructed to maintain their usual daily physical activities. The outcome variables measured included those related to cognitive function, dual-task cost (DTC), and gait performance., Results: The EXER-TC and TC groups performed better than the control group on the Chinese version of the Stroop Color and Word Test, the Trail Making Test Parts A and B, the one-back test, gait speed, and DTC of gait speed in cognitive dual-task conditions after training. However, there were no significant differences between the EXER-TC and TC groups. Compared with the control group, only the EXER-TC group experienced beneficial effects for the Montreal Cognitive Assessment., Conclusion: EXER-TC was comparable to traditional TC for enhancement of dual-task gait performance and executive function. These results suggested that the EXER-TC approach has potential therapeutic use in older adults with MCI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Cheng, Wei and Liao.)

The global application of engineered nanomaterials and nanoparticles (ENPs) in commercial products, industry, and medical fields has raised some concerns about their safety. These nanoparticles may gain access into rivers and marine environments through industrial or household wastewater discharge and thereby affect the ecosystem. In this study, we investigated the effects of silver nanoparticles (AgNPs) and zinc oxide nanoparticles (ZnONPs) on zebrafish embryos in aquatic environments. We aimed to characterize the AgNP and ZnONP aggregates in natural waters, such as lakes, reservoirs, and rivers, and to determine whether they are toxic to developing zebrafish embryos. Different toxic effects and mechanisms were investigated by measuring the survival rate, hatching rate, body length, reactive oxidative stress (ROS) level, apoptosis, and autophagy. Spiking AgNPs or ZnONPs into natural water samples led to significant acute toxicity to zebrafish embryos, whereas the level of acute toxicity was relatively low when compared to Milli-Q (MQ) water, indicating the interaction and transformation of AgNPs or ZnONPs with complex components in a water environment that led to reduced toxicity. ZnONPs, but not AgNPs, triggered a significant delay of embryo hatching. Zebrafish embryos exposed to filtered natural water spiked with AgNPs or ZnONPs exhibited increased ROS levels, apoptosis, and lysosomal activity, an indicator of autophagy. Since autophagy is considered as an early indicator of ENP interactions with cells and has been recognized as an important mechanism of ENP-induced toxicity, developing a transgenic zebrafish system to detect ENP-induced autophagy may be an ideal strategy for predicting possible ecotoxicity that can be applied in the future for the risk assessment of ENPs.

Speech frequency following responses (sFFRs) are increasingly used in translational auditory research. Statistically-based automated sFFR detection could aid response identification and provide a basis for stopping rules when recording responses in clinical and/or research applications. In this brief report, sFFRs were measured from 18 normal hearing adult listeners in quiet and speech-shaped noise. Two statistically-based automated response detection methods, the F-test and Hotelling's T 2 (HT 2 ) test, were compared based on detection accuracy and test time. Similar detection accuracy across statistical tests and conditions was observed, although the HT 2 test time was less variable. These findings suggest that automated sFFR detection is robust for responses recorded in quiet and speech-shaped noise using either the F-test or HT 2 test. Future studies evaluating test performance with different stimuli and maskers are warranted to determine if the interchangeability of test performance extends to these conditions.

Background: Silver nanoparticles (AgNPs) are considered a double-edged sword that demonstrates beneficial and harmful effects depending on their dimensions and surface coating types. However, mechanistic understanding of the size- and coating-dependent effects of AgNPs in vitro and in vivo remains elusive. We adopted an in silico decision tree-based knowledge-discovery-in-databases process to prioritize the factors affecting the toxic potential of AgNPs, which included exposure dose, cell type and AgNP type (i.e., size and surface coating), and exposure time. This approach also contributed to effective knowledge integration between cell-based phenomenological observations and in vitro/in vivo mechanistic explorations., Results: The consolidated cell viability assessment results were used to create a tree model for generalizing cytotoxic behavior of the four AgNP types: SCS, LCS, SAS, and LAS. The model ranked the toxicity-related parameters in the following order of importance: exposure dose > cell type > particle size > exposure time ≥ surface coating. Mechanistically, larger AgNPs appeared to provoke greater levels of autophagy in vitro, which occurred during the earlier phase of both subcytotoxic and cytotoxic exposures. Furthermore, apoptosis rather than necrosis majorly accounted for compromised cell survival over the above dosage range. Intriguingly, exposure to non-cytotoxic doses of AgNPs induced G2/M cell cycle arrest and senescence instead. At the organismal level, SCS following a single intraperitoneal injection was found more toxic to BALB/c mice as compared to SAS. Both particles could be deposited in various target organs (e.g., spleen, liver, and kidneys). Morphological observation, along with serum biochemical and histological analyses, indicated that AgNPs could produce pancreatic toxicity, apart from leading to hepatic inflammation., Conclusions: Our integrated in vitro, in silico, and in vivo study revealed that AgNPs exerted toxicity in dose-, cell/organ type- and particle type-dependent manners. More importantly, a single injection of lethal-dose AgNPs (i.e., SCS and SAS) could incur severe damage to pancreas and raise blood glucose levels at the early phase of exposure., (© 2022. The Author(s).)