bluuebunny/crossref_metadata_2025 huggingface dataset:
Dexmedetomidine attenuates postoperative spatial memory impairment after surgery by reducing cytochrome C
Authors: Sun Lina , Niu Kun , Guo Jian , Tu Jingru , Ma Baofeng , An Jianxiong
Published: March 2023

Background

Anesthesia and surgery can induce perioperative neurocognitive disorders (PND). Mitochondrial dysfunction has been proposed to be one of the earliest triggering events in surgery-induced neuronal damage. Dexmedetomidine has been demonstrated to attenuate the impairment of cognition in aged rats induced by surgery in our previous study.

Methods

Male Sprague-Dawley rats underwent hepatic apex resection under anesthesia with propofol to clinically mimic human abdominal surgery. The rats were divided into three groups: Control group, Model group and Dexmedetomidine (Dex) group. Cognitive function was evaluated with the Morris water maze (MWM), Open Field Test (OFT)and Novel object recognition task (NOR). Ultrastructural change in neuronal mitochondria was measured by transmission electron microscopy. Mitochondrial function was measured by mitochondrial membrane potential and activities of mitochondrial complexes. Neuronal morphology was observed with H&E staining and the activation of glial cells was observed by immunohistochemistry in the hippocampus. Protein levels were measured by Western blot (WB) and immunofluorescence at 3 and 7 days after surgery.

Results

Surgery-induced cognitive decline lasts three days, but not seven days after surgery in the model group. Transmission electron microscope showed the mitochondrial structure damage in the model group, similar changes were not induced in the Dex group. Dexmedetomidine may reverse the decrease in mitochondrial membrane potential and mitochondrial complex activity. Compared with the Control group, the expression of cytochrome c was significantly increased in model group by Western blot and immunofluorescence on days 3, but not day 7. Rats from the Model group expressed significantly greater levels of Iba-1 and GFAP compared with the Control group and the Dex group.

Conclusion

Dexmedetomidine appears to reverse surgery-induced behavior, mitigate the higher density of Iba-1 and GFAP, reduce the damage of mitochondrial structure and function by alleviating oxidative stress and protect mitochondrial respiratory chain, thus increasing cytochrome c oxidase (COX) expression and downregulate the expression of cytochrome c protein in the hippocampus of rats.
Low neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios predict favorable outcomes after endovascular treatment in acute basilar artery occlusion: subgroup analysis of the BASILAR registry
Authors: Liao Jia sheng , Guo Changwei , Zhang Bo , Yang Jie , Zi Wenjie , Li Jing lun
Published: March 2023

Background

Recently, the BAOCHE trial and ATTENTION trial registry have demonstrated the efficacy of endovascular treatment (EVT) in patients with acute basilar artery occlusion (BAO), however, the proportion of patients with favorable post-EVT outcomes remains low. The present study aimed to investigate the individual and joint prognostic values of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in patients with acute BAO who have undergone EVT.

Methods

We enrolled patients who underwent EVT from the BASILAR registry. Patients were divided into the following groups based on their modified Rankin Scale (mRS) scores at 90 days: favorable-outcome (mRS score: 0–3) and poor-outcome (mRS score: 4–6) groups. Multivariable logistic regression was performed to analyze the association of NLR and PLR with favorable post-EVT outcomes.

Results

In total, 585 patients with EVT were recruited. Of these, 189 and 396 patients were in the favorable-outcome and poor-outcome groups, respectively. According to the multivariable logistic regression analyses, both NLR (adjusted odds ratio [aOR], 0.950; 95% confidence interval [CI], 0.920–0.981; P = 0.002) and PLR (aOR, 0.997; 95% CI, 0.995–0.999; P = 0.002) were related to favorable post-EVT outcomes in patients with acute BAO. The optimal cutoff values for the NLR and PLR were 7.75 and 191, respectively. Furthermore, stratified analysis using the multivariable logistic regression model revealed that both NLR and PLR (NLR values ≥ 7.75 and PLR values ≥ 191) were associated with a low rate of favorable outcomes (aOR, 0.292; 95% CI, 0.173–0.494; P < 0.001).

Conclusions

Low NLR and PLR were both associated with favorable post-EVT outcomes in patients with acute BAO. Furthermore, the combined value of both inflammatory markers is potentially reliable in predicting clinical post-EVT outcomes.
Exosomal Lnc NEAT1 from endothelial cells promote bone regeneration by regulating macrophage polarization via DDX3X/NLRP3 axis
Authors: Chen Yuxuan , Wu Yuanhao , Guo Linlin , Yuan Shijie , Sun Jiaming , Zhao Kangcheng , Wang Jiecong , An Ran
Published: March 2023

Background

Bone regeneration is a complex procedure that involves an interaction between osteogenesis and inflammation. Macrophages in the microenvironment are instrumental in bone metabolism. Amount evidence have revealed that exosomes transmitting lncRNA is crucial nanocarriers for cellular interactions in various biotic procedures, especially, osteogenesis. However, the underlying mechanisms of the regulatory relationship between the exosomes and macrophages are awaiting clarification. In the present time study, we aimed to explore the roles of human umbilical vein endothelial cells (HUVECs)-derived exosomes carrying nuclear enrichment enriched transcript 1 (NEAT1) in the osteogenesis mediated by M2 polarized macrophages and elucidate the underlying mechanisms.

Results

We demonstrated HUVECs-derived exosomes expressing NEAT1 significantly enhanced M2 polarization and attenuated LPS-induced inflammation in vitro.Besides, the conditioned medium from macrophages induced by the exosomes indirectly facilitated the migration and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Mechanically, Exos carrying NEAT1 decreased remarkably both expression of dead-box helicase 3X-linked (DDX3X) and nod-like receptor protein 3 (NLRP3). The level of NLRP3 protein increased significantly after RAW264.7 cells transfected with DDX3X overexpression plasmid. Additionally, the knockdown of NEAT1 in exosomes partially counteracted the aforementioned effect of Exos. The results of air pouch rat model demonstrated that HUVECs-derived exosomes increased anti-inflammatory cytokines (IL-10) and decreased pro-inflammatory cytokines (IL-1β and IL-6) significantly in vivo, contributing to amelioration of LPS-induced inflammation. Afterwards, we further confirmed that the HUVECs-derived exosomes encapsulated in alginate/gelatin methacrylate (GelMA) interpenetrating polymer network (IPN) hydrogels could promote the bone regeneration, facilitate the angiogenesis, increase the infiltration of M2 polarized macrophages as well as decrease NLRP3 expression in the rat calvarial defect model.

Conclusions

HUVECs-derived exosomes enable transmitting NEAT1 to alleviate inflammation by inducing M2 polarization of macrophages through DDX3X/NLRP3 regulatory axis, which finally contributes to osteogenesis with the aid of alginate/GelMA IPN hydrogels in vivo. Thus, our study provides insights in bone healing with the aid of HUVECs-derived exosomes-encapsulated composite hydrogels, which exhibited potential towards the use of bone tissue engineering in the foreseeable future.
Adoption, implementation, and sustainability of early childhood feeding, nutrition and active play interventions in real-world settings: a systematic review
Authors: Gelman Rivka , Whelan Jillian , Spiteri Sheree , Duric Danijela , Oakhill Winnie , Cassar Samuel , Love Penelope
Published: March 2023

Background

Instilling healthy dietary habits and active play in early childhood is an important public health focus. Interventions supporting the establishment of nutrition and active play behaviours in the first years of life have shown positive outcomes and long-term cost-effectiveness, however, most are research trials, with limited evidence regarding real-world application. Implementation science theories, models and frameworks (TMFs) can guide the process of research translation from trial to real-world intervention. The application of TMFs within nutrition and active play intervention studies in early childhood (< 5 years) is currently unknown. This systematic review identified the use of TMFs and barriers/ enablers associated with intervention adoption, implementation, and sustainability in early childhood nutrition and active play interventions implemented under real-world conditions.

Methods

Six databases were searched for peer-reviewed publications between 2000–2021. Studies were included if primary outcomes reported improvement in diet, physical activity or sedentary behaviours amongst children aged < 5 years and interventions were delivered under real-world conditions within a community and/or healthcare setting. Two reviewers extracted and evaluated studies, cross checked by a third and verified by all authors. Quality assessment of included studies was completed by two authors using the Mixed Methods Appraisal Tool (MMAT).

Results

Eleven studies comprising eleven unique interventions were included. Studies represented low, middle and high-income countries, and were conducted across a range of settings. Five TMFs were identified representing four of Nilsen’s implementation model categories, predominantly ‘evaluation models’. Ninety-nine barriers/facilitators were extracted across the three intervention phases—Implementation (n = 33 barriers; 33 facilitators), Sustainability (n = 19 barriers;n = 9 facilitators), Adoption (n = 2 barriers;n = 3 facilitators). Identified barriers/facilitators were mapped to the five domains of the Durlak and DuPre framework, with ‘funding’, ‘compatibility’ and ‘integration of new programming’ common across the three intervention phases.

Conclusions

Findings demonstrate that there is no systematic application of TMFs in the planning, implementation and/or evaluation of early childhood nutrition and active play interventions in real-world settings, and selective and sporadic application of TMFs occurs across the intervention lifespan. This apparent limited uptake of TMFs is a missed opportunity to enhance real-world implementation success.

Trial registration

PROSPERO (CRD42021243841).
The effect of tibial component rotational alignment on clinical outcomes of mobile-bearing unicompartmental knee arthroplasty
Authors: Zhou Xiaoqiang , Sun Chao , Xu Renjie , Zhang Xiangxin , Yu Xiao
Published: March 2023

Background

The optimal tibial component rotational alignment in unicompartmental knee arthroplasty has not been defined. This study aimed to explore the effect of tibial component rotational alignment on the clinical outcomes of UKA.

Methods

Clinical and follow-up data from 269 patients were retrospectively analysed. They were assigned into Groups A (− 5° to 0°), B (0°–3°), C (3°–6°) and D (> 6°) according to the external rotation of the tibial component to Akagi’s line. The Knee Society Score clinical (KSS-c), Knee Society Score function (KSS-f), Forgotten Joint Score (FJS) and postoperative complications at 2 years postsurgically were analysed.

Results

The mean rotation of the tibial component relative to Akagi’s line in 269 patients was 4.56 ± 3.79°. There were 15, 84, 89 and 81 patients in Groups A, B, C and D, respectively. The postoperative KSS-c and KSS-f in Groups B and C were significantly higher than those in Group D. No significant differences in KSS-c and KSS-f were detected between Groups B and C. The postoperative FJS in Group B was significantly higher than that in Group C, which was significantly higher in Group C than in Group D. There were 5, 8 and 15 cases of postoperative knee pain in Groups B, C and D, respectively, and the difference was statistically significant.

Conclusion

Tibial component rotational alignment is of significance to Oxford Phase III UKA in patients. External rotation of the tibial component by 0°–3° is optimal to achieve satisfactory clinical outcomes.
Estimation of the proper gap ratio using preoperative radiography for posterior tibial slope maintenance in biplanar open wedge high tibial osteotomy
Authors: Yoon Jung-Ro , Koh Young Yoon , Lee Seung Hoon
Published: March 2023

Background

This study aimed to estimate the ratio of the anterior and posterior gaps before surgery that can minimize the posterior tibial slope (PTS) change through preoperative radiography, and to confirm whether the use of the block helps maintain the PTS during open wedge high tibial osteotomy (OWHTO).

Methods

Patients who underwent OWHTO between 2015 and 2018 were included. To measure optimal anterior gap (AG) and posterior gap (PG) ratio, hinge to medial tibial tuberosity length (HTL), total osteotomy length (TOL), and PTS were measured using knee AP X-ray. Real AG and PG were measured using postoperative knee computed tomography. Use of the block was also confirmed.

Results

Total 107 knees (95 patients) were included. The average ratio between HTL and TOL was 70.9%. The average ratio AG: PG was 72.9%. PTS increased significantly from 10.2° to 11.2° postoperatively (p = 0.006). When the difference in HTL: TOL and AG: PG, and the amount of PTS change were analyzed using linear regression, there was a statistically significant correlation (correlation coefficient: − 25.9; p < 0.001). There was no difference in AG: PG according to the use of the block (p = 0.882).

Conclusion

In OWHTO, PTS change can be minimized by estimating the ratio of the AG and PG using radiographs, and is was approximately 70%. If the ratio is increased by 10% from the predicted value, the PTS increases by approximately 2.6°. Using a block during OWHTO did not have a considerable advantage in terms of PTS maintenance compared to the group not using a block.

Level of evidence

Level IV.
A follow-up report on the published paper Social and clinical impact of COVID-19 on patients with fibrodysplasia ossificans progressiva
Authors: Wallace Hayley , Lee Rhonda H. , Hsiao Edward C.
Published: March 2023

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder associated with increased immune activity and severe, progressive heterotopic ossification. We previously described a cohort of 32 patients with FOP who were either exposed to SARS-CoV-2 or received a COVID-19 vaccine1 and showed that these patients did not develop heterotopic ossification after COVID-19 vaccination. Here, we present additional clinical data from new subjects and additional long-term follow-up from the first cohort. We enrolled 15 new subjects between August 24th, 2021 and May 17th, 2022 and collected additional self-reported outcomes. The larger cohort with 47 individuals encompassing 49 events showed that patients with FOP exhibited no additional change in FOP disease activity or flare activity resulting from COVID-19 infection or after receipt of a SARS-CoV-2 vaccine. Thus, although any vaccination carries a risk of inducing heterotopic ossification in patients with FOP, our results show that patients with FOP who choose to receive a COVID-19 vaccination may be able to tolerate the procedure without a high risk of heterotopic ossification when following the published guidelines.
Recent advances in modified poly (lactic acid) as tissue engineering materials
Authors: Castañeda-Rodríguez Samanta , González-Torres Maykel , Ribas-Aparicio Rosa María , Del Prado‑Audelo María Luisa , Leyva‑Gómez Gerardo , Gürer Eda Sönmez , Sharifi‑Rad Javad
Published: March 2023

As an emerging science, tissue engineering and regenerative medicine focus on developing materials to replace, restore or improve organs or tissues and enhancing the cellular capacity to proliferate, migrate and differentiate into different cell types and specific tissues. Renewable resources have been used to develop new materials, resulting in attempts to produce various environmentally friendly biomaterials. Poly (lactic acid) (PLA) is a biopolymer known to be biodegradable and it is produced from the fermentation of carbohydrates. PLA can be combined with other polymers to produce new biomaterials with suitable physicochemical properties for tissue engineering applications. Here, the advances in modified PLA as tissue engineering materials are discussed in light of its drawbacks, such as biological inertness, low cell adhesion, and low degradation rate, and the efforts conducted to address these challenges toward the design of new enhanced alternative biomaterials.
CLDN6 inhibits breast cancer metastasis through WIP-dependent actin cytoskeleton-mediated autophagy
Authors: Dong Yuan , Jin Qiu , Sun Minghao , Qi Da , Qu Huinan , Wang Xinqi , Quan Chengshi
Published: March 2023

Background

As a breast cancer suppressor gene, CLDN6 overexpression was found to inhibit breast cancer metastasis in our previous studies, but the specific mechanism remains unclear. This study aimed to clarify the role and mechanism of CLDN6 in inhibiting breast cancer metastasis.

Methods

Western blot, immunofluorescence and transmission electron microscopy were performed to detect autophagy. Wound healing, transwell assays and lung metastasis mouse models were used to examine breast cancer metastasis. Phalloidin staining and immunofluorescent staining were used to observe actin cytoskeleton. mRNA seq, RT-PCR, western blot, chromatin immunoprecipitation, dual luciferase reporter assay, co-immunoprecipitation and immunofluorescence were performed to define the molecular mechanism. The expression levels and clinical implication of CLDN6, WIP and LC3 in breast cancer tissues were evaluated using immunohistochemistry.

Results

We demonstrated that CLDN6 inhibited breast cancer metastasis through autophagy in vitro and vivo. We unraveled a novel mechanism that CLDN6 regulated autophagy via WIP-dependent actin cytoskeleton assembly. Through its PDZ-binding motif, overexpressed CLDN6 interacted with JNK and upregulated JNK/c-Jun pathway. C-Jun promoted WIP expression at the transcriptional level. Notably, we observed c-Jun transcriptionally upregulated CLDN6 expression, and there was a positive feedback loop between CLDN6 and JNK/c-Jun. Finally, we found that CLDN6, WIP and LC3 expression correlated with each other, and WIP expression was significantly associated with lymph node metastasis of breast cancer patients.

Conclusions

The data provide a new insight into the inhibitory effects of CLDN6-mediated autophagy on breast cancer metastasis, and revealed the new mechanism of CLDN6 regulating autophagy through WIP-dependent actin cytoskeleton. Our findings enrich the theoretical basis for CLDN6 as a potential biomarker for breast cancer diagnosis and therapy.
Bioconversion of ferulic acid and vanillin to vanillic acid by cold-adapted Paraburkholderia aromaticivorans AR20-38: impact of culture conditions
Authors: Ludwikowski Thomas M. , Wagner Andreas O. , Margesin Rosa
Published: March 2023

Purpose

Biovalorization of lignin-derived aromatic monomers such as ferulic acid (FA) has attracted considerable interest. The cold-adapted strain Paraburkholderia aromaticivorans AR20-38 converts FA to the value-added product vanillic acid (VA), without further VA degradation. The efficiency of the bioconversion of FA to VA was optimized by studying culture conditions.

Methods

Various cultivation parameters (agitation, temperature, FA concentration, nutrient supplementation) were assessed to increase biomass production and shorten the cultivation time, while obtaining high VA production yields. The fate of the intermediate vanillin was also studied. Lignin monomers and degradation products (FA, vanillin, VA) were quantified via UV/Vis-HPLC.

Result

Full bioconversion of 5 mM FA occurred over a broad temperature range of 5–30 °C. Concentrations up 30 mM FA were utilized as the sole carbon source at 20 °C. Molar VA yields (> 90%) produced from 5 to 12.5 mM FA and from 15 to 17.5 mM FA (82–87%) were not significantly different at 10 °C and 20 °C. The supplementation of the mineral medium with monosaccharides (glucose, fructose, mannose) and/or N-rich complex compounds (yeast extract, casamino acids) resulted in high biomass production, accelerated FA bioconversion, and high molar yields (96–100%). The presence of the N-rich compounds alone or in combination with glucose reduced the incubation time necessary to convert FA to VA. Vanillin, formed as an intermediate during FA degradation, was consumed and converted to VA before FA metabolization, when added in combination with FA. Vanillin bioconversion was significantly accelerated in the presence of glucose.

Conclusion

The variation of culture conditions improved the efficiency of the studied strain to convert FA via vanillin to VA and demonstrated remarkable FA bioconversion under varying environmental conditions, especially temperature, substrate concentration, and nutrient availability, which is of importance for potential future application.
Transmit and receive hybrid beamforming design for OFDM dual-function radar-communication systems
Authors: Zeng Junjie , Liao Bin
Published: March 2023

This article investigates the design of hybrid digital and analog transmit/receive beamformers for orthogonal frequency division multiplexing dual-function radar-communication system. Specifically, we model the hybrid beamforming design by simultaneously optimizing the spectrum efficiency of communication and approximate output signal-to-interference noise ratio of radar sensing, through a flexible performance tradeoff. Due to the coupling relationship among the beamformers in the hybrid structure and the independence of signals in different frequency bands, the resultant optimization problem is NP-hard. Hence, a consensus alternating direction method of multipliers approach is designed to tackle the difficulty. The transmit hybrid beamformer is obtained by introducing auxiliary variables and exploiting the block continuous upper bound minimization method. Then, the receive beamformer can be optimized via generalized eigenvalue decomposition. Numerical simulations are provided to demonstrate the effectiveness of the proposed scheme.
Magnitude and determinants of inappropriate prescribing of antibiotics in dentistry: a nation-wide study
Authors: Rodríguez-Fernández Almudena , Vázquez-Cancela Olalla , Piñeiro-Lamas María , Herdeiro María Teresa , Figueiras Adolfo , Zapata-Cachafeiro Maruxa
Published: March 2023

Background

Dentist play an important role in misuse of antibiotics. Identification of the dental activities linked to the misuse of antibiotics is important for improving dentists’ prescribing quality. The aim of the study was to quantify the magnitude of inappropriate antibiotic prescribing by dentists in Spain and identify the characteristics, knowledge and attitudes that influence prescribing quality.

Material and methods

We conducted a cross-sectional, questionnaire-based study on dentists in Spain, assessing prescribing quality (dependent variable) on the basis of their responses about the prescription of antibiotics in 14 clinical situations. As the independent variables, we assessed professional characteristics and attitudes (lack of knowledge, fear, complacency, scheduling problems, and economic benefit) measured on a Likert scale. Odds Ratios (OR) (95%CI) were calculated using logistic regression.

Results

A total of 878 participants were included in the analysis. Half of all dentists displayed inappropriate antibiotic prescribing habits in more than 28.6% (10/14) of the clinical situations posed (interquartile range 57–79%). Prescribing quality increased when resistance was perceived as a public health problem (OR 0.88, 95% CI: 0.79–0.97), and decreased in response to fear (OR 1.12, 95% CI:1.07–1.18) or the pursuit of economic benefit (OR 1.07, 95% CI 1.01–1.14). Having over 30 years’ experience (OR 4.58, 95% CI:1.80–12.48) and/or practising in the field of prosthodontics as opposed to endodontics (OR 2.65, 95% CI:1.26–5.71) were associated with worse prescribing quality.

Conclusions

Antibiotics are the most commonly prescribed drugs in dentistry, and in many cases this prescription is inappropriate. Our findings shows that modifiable factors influence prescribing quality among dentists in Spain. These may be use for designing educational and training programmes for dentists.
Synthetic bacterial consortia transplantation for the treatment of Gardnerella vaginalis-induced bacterial vaginosis in mice
Authors: Li Yunxia , Zhu Wei , Jiang Yan , Lessing Duncan James , Chu Weihua
Published: March 2023

Bacterial vaginosis (BV) is a disease caused by vaginal microbiota dysbiosis. Here, we propose the use of synthetic bacterial consortia transplantation (SBCT) for the treatment of Gardnerella vaginalis-induced BV mice. The results showed that SBCT significantly reduced vaginal tissue damage and restored the vaginal microbiota, decreased the secretion of pro-inflammatory cytokines (IL-1β and IL-8), and suppressed NF-κB activation. IL-17, iNOS, and COX-2 expression in vaginal tissue were also down-regulated. However, IL-10 and Foxp3 showed up-regulated expression in mice. Compared with vaginal microbiota transplantation (VMT), results indicated that VMT was more effective than SBCT in suppressing G. vaginalis-induced inflammation. The obtained results suggest that synthetic bacterial consortia might be used as a potential biotherapeutic agent for the treatment of G. vaginalis-induced bacterial vaginosis.
Cleaning iron rust compounds from cotton textiles: application to Qing Dynasty armor
Authors: Miao Binbin , Zhao Zuoyong , Guo Pengli , Li Haomiao , Wang Yueping
Published: March 2023

A composite structure consisting of cotton fabric and iron sheet was widely used in Qing Dynasty armor. Due to iron sheet corroding easily, the surfaces of cotton fabric were covered with numerous rust compounds, which has a significant negative impact on the relics. In this paper, by taking Qing Dynasty armor relics as the research object, the cleaning process was reported for cotton fabrics stained with corrosion products. Using an orthogonal experiment, rust stained model samples were used to explore a specialized and efficient cleaning process. Results show that the cleaning reagents, including ascorbic acid (mass fraction 10.0 g/L), ethylenediaminetetraacetic acid disodium salt (EDTA-2Na, mass fraction 10.0 g/L), and the surfactant composed of 70% rhamnolipid and 30% alkyl glycoside (mass fraction 8.0 g/L), could fully exert a synergistic effect. After treatment, the color difference (ΔE) value between the cleaned sample and the unstained sample is only 3.81. A series of comprehensive experimental results demonstrate that the cleaning procedure is effective and safe. There are almost no rust compounds and cleaning reagent residues, and no damage to cotton fiber. The reported wet cleaning process, aided by soft bristle brush, achieved good cleaning results, indicating that the process can be used to clean rust stain pollutants in Qing dynasty cotton armor.
Incisor irregularity and dental arch dimensions changes in subjects with different severity of anterior crowding: a 37-year follow-up
Authors: Gambardela-Tkacz Caroline Martins , Alcaraz Gabriela , Cotrin Paula , de Freitas Karina Maria Salvatore , Moura Willana , Janson Guilherme , Garib Daniela , de Freitas Marcos Roberto
Published: March 2023

Background

Occlusal stability is one of the goals of orthodontic treatment, and keeping teeth aligned in the long term is a challenge for the orthodontist. This study aimed to compare the long-term incisors irregularity and dental arches dimensions changes in subjects treated with 4 premolar extractions with different pretreatment Little's irregularity index (LII). The knowledge of long-term outcomes is evidence-based information for the prognosis of future treatments.

Methods

In total, 41 treated subjects were divided into two groups according to mandibular Little irregularity value at pretreatment (mild or severe). The maxillary and mandibular LII, transversal, and longitudinal widths were assessed at pretreatment, posttreatment, and 37-year posttreatment. Chi-square and independent t tests were used for intergroup comparison.

Results

The groups presented similar behavior for all stages of maxillary and mandibular arch dimensions changes. Maxillary irregularity was corrected in both groups after treatment, and the alignment was acceptable in the long term. In the mild group, the mandibular incisor irregularity returned to pretreatment values in the long term. The mandibular LII increased in the severe group but did not return to pretreatment values in the long term.

Conclusions

The mild crowding group presented proportionally more relapse of mandibular incisor irregularity than the severe crowding group in the long term. Even so, the correction of mild and severe crowding with the extraction of 4 premolars showed satisfactory results in the long term, even with the presence of maturational changes and relapse.
Thermal modeling and simulation of a single-flash geothermal power plant involving non-condensable gas: a case study of Kamojang geothermal field in Garut, West Java, Indonesia
Authors: Sufyana Candra Mecca , Akbar Fiki Taufik , Srigutomo Wahyu
Published: March 2023

The presence of non-condensable gases (NCGs) in a geothermal fluid disrupts the vacuum process in the condenser, reducing turbine efficiency and decreasing the total power output of the geothermal power plant (GPP). Therefore, to optimize the thermodynamic efficiency of a GPP, NCGs should be removed using a gas removal system. Since there is a substantial lack of design and simulation software for a GPP including NCG removal alternatives, in this study, we aimed to model and develop a software-based interface to simulate mass and energy balance involving an NCG fraction in a single-flash GPP as well as examine the thermodynamic performance of the gas removal system, which is the most important step in the planning and designing phase of a GPP. This software was validated using outputs of Kamojang GPP Units 2, 3, and 4 located at Kamojang geothermal field, Garut, West Java, Indonesia. Units 2 and 3 use two ejectors which are installed in series, and Unit 4 utilizes a hybrid system (HS) that is mostly a combination of vacuum pumps and a steam jet ejector (SJE). Our results showed that Kamojang GPP Units 2 and 3 generate 55.295 MW of power with an absolute error of 0.53%, whereas Unit 4 generates 60.218 MW of power with a 0.36% absolute error concerning the field data. These results correspond with the expected minimum error; therefore, our model’s parameters are considered valid and can be used for simulation. We found that using the simulation, the total steam saved by the HS at Kamojang GPP Units 2 and 3 was 534 kW. Furthermore, the net power production was reduced by 1.6% for the HS and 2.03% for the SJE with every 1% increase in the NCG fraction. The power requirement of the vacuum pumps remained less than the power generated by the motive steam which the ejector requires to dispose of the same amount of NCG, indicating that Kamojang GPP Units 2 and 3 will be more efficient if an HS is used.
Pharmacokinetics and brain distribution of the therapeutic peptide liraglutide by a novel LC–MS/MS analysis
Authors: Oh Hyeon Seok , Choi Minkyu , Lee Tae Suk , An Yejin , Park Eun Ji , Kim Tae Hwan , Shin Soyoung , Shin Beom Soo
Published: March 2023

Liraglutide is a glucagon-like peptide-1 (GLP-1) analog that has been utilized for the treatment of type 2 diabetes mellitus. Liraglutide at a higher dose also shows beneficial effects in weight loss, which prompted its widespread use as an anti-obesity drug. The potential of liraglutide to treat Alzheimer’s disease and cognitive impairment has also been suggested. Nevertheless, the pharmacokinetics of liraglutide, including its distribution to the brain, has not been fully characterized. Therefore, this study aimed to develop a simple and sensitive bioanalytical method using liquid chromatography–tandem mass spectrometry (LC–MS/MS) and determine the pharmacokinetics and brain distribution of liraglutide in rats. Liraglutide in the rat plasma and brain tissue homogenates was extracted by protein precipitation using methanol. A gradient elution profile was used for chromatographic separation with mobile phases comprising 0.3% formic acid in water and 0.3% formic acid in acetonitrile. The mass spectrometry was operated in the positive electrospray ionization with multiple reaction monitoring mode. The lower limit of quantification of the present LC–MS/MS was 1 ng/mL in the plasma and 2 ng/mL in the brain tissue. Following intravenous injection (0.05 mg/kg, n = 5), plasma concentrations of liraglutide decreased monoexponentially with an average half-life of 3.67 h. The estimated absolute bioavailability of liraglutide after subcutaneous injection was 13.16%. Brain distribution of liraglutide was not significant, with the tissue-to-plasma partition coefficient (Kp) of liraglutide less than 0.00031. However, the concentrations of liraglutide were significantly different in the different brain regions following IV injection. In the brain, liraglutide concentrations were the highest in the hypothalamus, followed by the cerebellum and cerebrum. The present LC–MS/MS assay and the pharmacokinetic results may be helpful to understand better the effect of liraglutide in the brain for further preclinical and clinical studies of liraglutide.
Analysis of urinary C–C motif chemokine ligand 14 (CCL14) and first-generation urinary biomarkers for predicting renal recovery from acute kidney injury: a prospective exploratory study
Authors: Qian Ben-Shu , Jia Hui-Miao , Weng Yi-Bing , Li Xin-Cheng , Chen Chao-Dong , Guo Fang-Xing , Han Yu-Zhen , Huang Li-Feng , Zheng Yue , Li Wen-Xiong
Published: March 2023

Background

Acute kidney injury (AKI) is a frequent syndrome in the intensive care unit (ICU). AKI patients with kidney function recovery have better short-term and long-term prognoses compared with those with non-recovery. Numerous studies focus on biomarkers to distinguish them. To better understand the predictive performance of urinary biomarkers of renal recovery in patients with AKI, we evaluated C–C motif chemokine ligand 14 (CCL14) and two first-generation biomarkers (cell cycle arrest biomarkers and neutrophil gelatinase-associated lipocalin) in two ICU settings.

Methods

We performed a prospective study to analyze urinary biomarkers for predicting renal recovery from AKI. Patients who developed AKI after ICU admission were enrolled and urinary biomarkers including tissue inhibitor of metalloproteinase-2 (TIMP-2), insulin-like growth factor-binding protein 7 (IGFBP7), CCL14, and neutrophil gelatinase-associated lipocalin (NGAL) were detected on the day of AKI diagnosis. The primary endpoint was non-recovery from AKI within 7 days. The individual discriminative ability of CCL14, [TIMP-2] × [IGFBP7] and NGAL to predict renal non-recovery were evaluated by the area under receiver operating characteristics curve (AUC).

Results

Of 164 AKI patients, 64 (39.0%) failed to recover from AKI onset. CCL14 showed a fair prediction ability for renal non-recovery with an AUC of 0.71 (95% CI 0.63–0.77, p < 0.001). [TIMP-2] × [IGFBP7] showed the best prediction for renal non-recovery with an AUC of 0.78 (95% CI 0.71–0.84, p < 0.001). However, NGAL had no use in predicting non-recovery with an AUC of 0.53 (95% CI 0.45–0.60, p = 0.562). A two-parameter model (non-renal SOFA score and AKI stage) predicted renal non-recovery with an AUC of 0.77 (95% CI 0.77–0.83, p = 0.004). When [TIMP-2] × [IGFBP7] was combined with the clinical factors, the AUC was significantly improved to 0.82 (95% CI 0.74–0.87, p = 0.049).

Conclusions

Urinary CCL14 and [TIMP-2] × [IGFBP7] were fair predictors of renal non-recovery from AKI. Combing urinary [TIMP-2] × [IGFBP7] with a clinical model consisting of non-renal SOFA score and AKI stage enhanced the predictive power for renal non-recovery. Urinary CCL14 showed no significant advantage in predicting renal non-recovery compared to [TIMP-2] × [IGFBP7].
Blind study site assessment of shear-wave velocity at Kumamoto City, Japan, using direct-fitting SPAC methods
Authors: Asten Michael , Askan Aysegul , Karimzadeh Shaghayegh
Published: March 2023

The study used data acquired by the ESG6 Blind Prediction Step BP1 Working Group for purposes of facilitating a comparison of interpretation methods for obtaining shear-wave velocity profiles (Vs) from array observations of microtremor (passive seismic) noise. This work uses the direct-fitting MMSPAC method and the krSPAC method on passive seismic data supplied from four seven-station nested triangular arrays with apertures ranging from 1 to 962 m, located within Kumamoto City, Japan. The data allow a useful frequency range of 38 Hz down to 0.3 Hz, giving depth sensitivities from 2 m to > 1000 m. Results are presented as a seven-layer model which has time-averaged shear wave velocities for top 30 m and 300 m of Vs30 = 189 m/s and Vs300 = 584 m/s, respectively. HVSR spectra show two significant peaks at 1.2 and 0.35 Hz which are indicative of major Vs contrasts at depths 26 m and 750 m. The MMSPAC method (and its krSPAC variant) also proved viable on one asymmetric array where four of the seven stations were corrupted by incoherent low-frequency noise. Indications of a lateral variation in Vs could be detected due to the non-concentric geometry of the four arrays, and also from variations in HVSR spectra at stations of the largest array. Further analysis in step 4 of the blind trials, making use of geological data and a Preferred model supplied to participants, showed apparent discrepancies between the Preferred and our BP1 model for the upper 40 m where a supplied PS log appears to be inconsistent with geological data and the blind BP1 model. At low frequencies 0.5–2.5 Hz dispersion data and the BP1 model suggest that use of the Rayleigh effective mode is superior to use of the fundamental mode in deducing the Vs model at depths below 100 m. The method of direct fitting of model and observed SPAC spectra used in MMSPAC also enabled the use of a bandwidth 0.5–38 Hz for interpretation, which is a wider bandwidth than that achieved by other participants for use of passive seismic data alone.

Graphical Abstract
Familial affections vis-à-vis filial piety: the ethical challenges facing eldercare under neo-familism in contemporary China
Authors: Yan Yunxiang
Published: March 2023

The present study demonstrates that the values and practices of neo-familism are altering the ethical foundation of eldercare in a similar way as they did in other areas of family life. The chief ethical challenges include the shift of the center of gravity from ancestors to children or grandchildren, the inversion of the hierarchical order within the oneness of parent–child identity, the saliency of eldercare qinqing discourse derived from the intimate and emotional turn in family life, the importance of family history as the keeper of the balance sheet of qinqing interactions, and the emerging pursuit of distributive justice in the sphere of private life. Working together, these challenges have effectively destabilized the principle of filial piety as the ethical foundation of eldercare and, at the same time, they have contributed to the formation of a qinqing ethics of eldercare. The article ends with a sketch of the main features of the emerging qinqing ethics and a call for more innovative thinking out of the gatekeeping box of filial piety paradigm in the sociology of Chinese family.
Refractory right ventricular myocarditis induced by immune checkpoint inhibitor despite therapy cessation and immune suppression
Authors: Mohammad Khan O. , Fanous Hanna , Vakamudi Sneha , Liu Yan
Published: March 2023

Background

Immune checkpoint inhibitors (ICIs) are currently widely used for treatment of various types of cancers. ICI-induced myocarditis, though uncommon, accounts for high risk of major adverse cardiac events and mortality, which makes appropriate diagnosis important. We here present a unique, challenging case of ICI-induced, refractory and isolated right ventricular (RV) myocarditis.

Case presentation

A 32-year-old female with breast cancer presented with newly onset chest pain and dyspnea shortly after initiation of Pembrolizumab. Coronary angiography showed normal coronary arteries and a cardiac magnetic resonance (CMR) revealed myocarditis involving the right ventricle with chamber dilation and severe dysfunction. ICI therapy was stopped, and high dose steroid therapy was initiated and symptoms resolved. However, three months after initial presentation, the patient was hospitalized for DKA and decompensated right heart failure, and a repeat cardiac MRI at that time showed recurrent, isolated right ventricular myocardial inflammation/edema without LV involvement. High dose steroid therapy was started again and at 6-month follow up, surveillance CMR continued to show persistent right-sided myocarditis, patient was eventually treated with Abatacept with resolution of HF symptoms, RV dysfunction and biomarkers at 10-month follow up.

Conclusions

We describe a unique case of isolated ICI-induced right ventricular myocarditis leading to right ventricular failure, that was refractory despite ICI therapy cessation and immune suppression by repeated high dose steroids. Co-stimulatory pathway modulation with Abatacept eventually lead to the normalization of RV function and dilation ten months after initial myocarditis onset.
Three perspectives on learning in a simulated patient scenario: a qualitative interview study with student, simulated patient, and teacher
Authors: Erici Sten , Lindqvist Daniel , Lindström Mats B. , Gummesson Christina
Published: March 2023

Introduction

Patient simulation can be useful for medical students in developing communication skills for vulnerable situations. Three participants are primarily involved in the patient simulation activities: the student, the simulated patient (SP), and the teacher. We here aimed to explore these participants’ perceptions of learning in a patient simulation scenario.

Methods

We conducted individual interviews with eight students, three teachers, and one SP at a psychiatry placement of a Medical Doctor Program (5th year). During the interviews we asked the participants to watch a video of their participation in a patient simulation session. Thus, we obtained three perspectives on each of the eight recordings. We analysed our data with qualitative content analysis.

Results

Three themes were generated: identity formation, collaborative learning, and learning intentions. This highly emotional scenario forced students out of their comfort zone, to the intersection of their roles as private person and professional. The SP perceived the collaborative creation of the scenario as significant learning. The teacher took a professional position and perceived the learning in the perspective of a future colleague.

Conclusions

The mutually created emotionally loaded scenario was found to be important from all three perspectives, forcing the students to identify unexpected ways of communicating.

This possibly enhanced their professional identity development. Implications for future research can be to explore the process of skills transfer.
Group 2 innate lymphoid cells and their surrounding environment
Authors: Naito Maiko , Kumanogoh Atsushi
Published: March 2023

Since the discovery of group 2 innate lymphoid cells (ILC2s) in 2010, subsequent studies have revealed their developmental pathways, mechanisms of activation and regulation, and immunological roles in tissue homeostasis and tissue-specific diseases in various organs. Although ILC2s are known to express tissue-specific features depending on where they reside, how the surrounding environment affects the functions of ILC2s remains to be fully elucidated. Recent histologic analyses revealed that ILC2s resides in specific perivascular regions in peripheral tissues with their function being controlled by the surrounding cells via cytokines, lipid mediators, neurotransmitters, and cell–cell interactions through surface molecules. This review summarizes the interactions between ILC2s and surrounding cells, including epithelial cells, neurons, immune cells, and mesenchymal cells, with the objective of promoting the development of novel diagnostic and therapeutic methods for ILC2-related diseases.
A response to the terms in Shah et al's ‘Neurodevelopmental disorders and neurodiversity: definition of terms from Scotland's National Autism Implementation Team’
Authors: Chown Nick , Annable Jennifer Layton , Beardon Luke , Howard Nik
Published: March 2023

The Scottish National Autism Implementation Team's neurodiversity terms are a valiant, but flawed, attempt to reconcile different worldviews on neurodiversity. The aim of harmonising different perspectives is laudable; however, we disagree with the use of ‘societal norms’ in the authors’ framework of terms and challenge some of their proposed definitions.
Intraoperative Kounis Syndrome and Fixation Errors: A Case Report
Authors: Ogaz Trent A. , Sweitzer BobbieJean
Published: March 2023

Postinduction hypotension, though frequently due to anesthetic medications, has a variety of causes. We present a case of presumed intraoperative Kounis syndrome, or anaphylaxis-induced coronary vasospasm, in which the patient’s perioperative course was initially attributed to anesthesia-induced hypotension and iatrogenic rebound hypertension leading to Takotsubo cardiomyopathy. A second anesthetic event with immediate recurrence of hypotension after the patient received levetiracetam appears to confirm the diagnosis of Kounis syndrome. In this report, we discuss the fixation error that led to this patient’s original misdiagnosis.
Bring Us in Good Ale
Authors: Kopp Peter A.
Published: March 2023

This essay documents the century-long efforts of Peter Darby, Ernest S. Salmon, and Ray Neve, all of whom were directors of England's Hop Research Program. While these scientists engaged in myriad projects, the central story surrounds the development and release of hybrid hop varieties for use in beer. In contrast with the brewing industry that turned toward mechanization and industrial advancements in the twentieth century, the English hop breeding program steadily relied on hand-pollinating characteristic of Mendelian genetics. Crossbreeding, or hybridization, of hops (and scores of other dioicous plants—that is, those with two distinct sexes) traditionally occurred with scientists selecting specimens that exhibited desirable traits that could be traced to their hereditary makeup. The process was painstakingly slow, requiring countless dustings of pollen from male plants onto female flowers. Darby, Salmon, and Neve engaged in this process thousands of times before deciding on which offspring to select from the greenhouses to transplant into fields. Their promising and successful specimens today populate England's experimental hop garden for their potential in brewing or breeding future crosses; the most outstanding progeny can be found in beers near and far.