bluuebunny/crossref_metadata_2025 huggingface dataset:
DNA damage stress-induced translocation of mutant FUS proteins into cytosolic granules and screening for translocation inhibitors
Authors: Nogami Masahiro , Sano Osamu , Adachi-Tominari Keiko , Hayakawa-Yano Yoshika , Furukawa Takako , Iwata Hidehisa , Ogi Kazuhiro , Okano Hideyuki , Yano Masato
Published: December 2022

Fused in sarcoma/translated in liposarcoma (FUS) is an RNA-binding protein, and its mutations are associated with neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), through the DNA damage stress response, aberrant stress granule (SG) formation, etc. We previously reported that translocation of endogenous FUS into SGs was achieved by cotreatment with a DNA double-strand break inducer and an inhibitor of DNA-PK activity. In the present study, we investigated cytoplasmic SG formation using various fluorescent protein-tagged mutant FUS proteins in a human astrocytoma cell (U251) model. While the synergistic enhancement of the migration of fluorescent protein-tagged wild-type FUS to cytoplasmic SGs upon DNA damage induction was observed when DNA-PK activity was suppressed, the fluorescent protein-tagged FUSP525L mutant showed cytoplasmic localization. It migrated to cytoplasmic SGs upon DNA damage induction alone, and DNA-PK inhibition also showed a synergistic effect. Furthermore, analysis of 12 sites of DNA-PK–regulated phosphorylation in the N-terminal LC region of FUS revealed that hyperphosphorylation of FUS mitigated the mislocalization of FUS into cytoplasmic SGs. By using this cell model, we performed screening of a compound library to identify compounds that inhibit the migration of FUS to cytoplasmic SGs but do not affect the localization of the SG marker molecule G3BP1 to cytoplasmic SGs. Finally, we successfully identified 23 compounds that inhibit FUS-containing SG formation without changing normal SG formation.

Highlights

Characterization of DNA-PK-dependent FUS stress granule localization.

A compound library was screened to identify compounds that inhibit the formation of FUS-containing stress granules.
Association of caffeine intake with all-cause and cardiovascular mortality in elderly patients with hypertension
Authors: Chen Shuaijie , Li Jing , Gao Menghan , Li Duanbin , Shen Ruming , Lyu Lingchun , Shen Jiayi , Shen Xiaohua , Fu Guosheng , Wei Tiemin , Zhang Wenbin
Published: December 2022

Background

Caffeine is widely consumed not only in coffee but also in soft drinks and tea. However, the long-term health effects of caffeine are still controversial, especially in people with high cardiovascular risk such as elderly patients with hypertension.

Methods

This study analyzed data from the National Health and Nutrition Examination Survey 2003–2018. Caffeine intake was calculated by two 24-h dietary recall interviews. Complex sampling-weighted multivariable Cox proportional hazards models were used to compare the hazard ratios (HRs) of all-cause and cardiovascular mortality in elderly hypertensive patients with different caffeine intake (<10, 10 to <100, 100 to <200, 200 to <300, and ≥300 mg/day).

Results

This study included 6,076 elderly hypertensive patients. The mean ± standard error follow-up duration was 6.86 ± 0.12 years. During this period, a total of 2,200 all-cause deaths occurred, of which 765 were cardiovascular deaths. Taking patients with caffeine intake < 10 mg/day as a reference, patients with moderate caffeine intake (200 to <300 mg/day) had a lower risk of all-cause (HR, 0.70 [95% CI, 0.56–0.87]) and cardiovascular (HR, 0.55 [95% CI, 0.39–0.77]) mortality. The benefit of reducing all-cause mortality risk was significant in female patients (HR, 0.65 [95% CI, 0.50–0.85]) or patients with well-controlled blood pressure (HR, 0.63 [95% CI, 0.46–0.87]), but not in male patients or patients with poorly controlled blood pressure. In addition, non-linear relationship analysis also showed that moderate caffeine intake had the lowest HRs of all-cause (Non-linear p = 0.022) and cardiovascular mortality (Non-linear p = 0.032) in the present study.

Conclusion

Moderate caffeine intake is associated with reduced risk of all-cause and cardiovascular mortality in elderly hypertensive patients.
Efficacy, safety, and controversy of ultrasound-guided radiofrequency ablation in the treatment of T1N0M0 papillary thyroid carcinoma
Authors: Yi Zhang , Siyu Li , Lijun Fu , Danhua Zhang , Jianhua Li , Xinguang Qiu
Published: December 2022

Objective

To evaluate the safety effect, and controversy on the treatment outcomes of radiofrequency ablation (RFA) for T1N0M0 papillary thyroid carcinoma (PTC).

Materials and methods

This study is assessed the medical records of 142 patients with primary T1N0M0 PTC tumors after RFA between 2014 and 2022. 4 patients underwent delayed surgery (DS) after RFA and 411 T1N0M0 patients underwent DS were recorded. Outcomes were compared between RFA and DS groups after propensity score matching (PSM).

Results

The maximal diameter (MD) and volume (V) increased in months 1 (P < 0.01) and reduced after the 6-month follow-up (all P < 0.01). The disappearance and disease progression rates were 53.5% and 2.1%, respectively. The complication and disease progression rates had no significant difference between RFA and DS (P>0.05). In some cases, the tumors were not fully inactivated after RFA, and the central compartment lymph node (CCLN) were metastasis. The CCLN metastasis rate was 13.4%. MD, V and clustered calcifications were independent risk factors for CCLN metastasis by univariate analysis.

Conclusions

RFA is an effective and safe treatment option in selected patients with solitary T1N0M0 PTC. There are the risks of tumor incompletely ablated and CCLN metastasis.
Combination of the parent analogue of remdesivir (GS-441524) and molnupiravir results in a markedly potent antiviral effect in SARS-CoV-2 infected Syrian hamsters
Authors: Abdelnabi Rana , Maes Piet , de Jonghe Steven , Weynand Birgit , Neyts Johan
Published: December 2022

Remdesivir was the first antiviral drug to be approved for the treatment of severe COVID-19; followed by molnupiravir (another prodrug of a nucleoside analogue) and the protease inhibitor nirmatrelvir. Combination of antiviral drugs may result in improved potency and help to avoid or delay the development of resistant variants. We set out to explore the combined antiviral potency of GS-441524 (the parent nucleoside of remdesivir) and molnupiravir against SARS-CoV-2. In SARS-CoV-2 (BA.5) infected A549-Dual™ hACE2-TMPRSS2 cells, the combination resulted in an overall additive antiviral effect with a synergism at certain concentrations. Next, the combined effect was explored in Syrian hamsters infected with SARS-CoV-2 (Beta, B.1.351); treatment was started at the time of infection and continued twice daily for four consecutive days. At day 4 post-infection, GS-441524 (50 mg/kg, oral BID) and molnupiravir (150 mg/kg, oral BID) as monotherapy reduced infectious viral loads by 0.5 and 1.6 log10, respectively, compared to the vehicle control. When GS-441524 (50 mg/kg, BID) and molnupiravir (150 mg/kg, BID) were combined, infectious virus was no longer detectable in the lungs of 7 out of 10 of the treated hamsters (4.0 log10 reduction) and titers in the other animals were reduced by ∼2 log10. The combined antiviral activity of molnupiravir which acts by inducing lethal mutagenesis and GS-441524, which acts as a chain termination appears to be highly effective in reducing SARS-CoV-2 replication/infectivity. The unexpected potent antiviral effect of the combination warrants further exploration as a potential treatment for COVID-19.
Qing-Re-Xiao-Zheng-Yi-Qi formula relieves kidney damage and activates mitophagy in diabetic kidney disease
Authors: Wu Qiaoru , Yan Runze , Yang Hanwen , Wang Yixuan , Zhang Chao , Zhang Jiale , Cui Zhaoli , Wang Yaoxian , Sun Weiwei
Published: December 2022

Introduction: Qing-Re-Xiao-Zheng-Yi-Qi Formula is an effective prescription in diabetic kidney disease treatment, we have confirmed the efficacy of Qing-Re-Xiao-Zheng therapy in diabetic kidney disease through clinical trials. In this study, we investigated the mechanisms of Qing-Re-Xiao-Zheng-Yi-Qi Formula in the treatment of diabetic kidney disease.

Methods: We used Vanquish UHPLCTM to analyze the chemical profiling of Qing-Re-Xiao-Zheng-Yi-Qi Formula freeze-dried powder. We constructed diabetic kidney disease rat models induced by unilateral nephrectomy and high-dose streptozocin injection. We examined blood urea nitrogen, serum creatinine, serum glucose, total cholesterol, triglyceride, serum total protein, albumin, alanine aminotransferase, aspartate aminotransferase and 24 h urinary total protein in diabetic kidney disease rats. The renal pathological changes were observed by HE, Masson, PAS stanning and transmission electron microscopy. The levels of fibrosis-related proteins and mitophagy-related proteins were detected by western blot analysis. We also conducted an immunofluorescence co-localization analysis on podocytes to further investigate the effect of Qing-Re-Xiao-Zheng-Yi-Qi Formula treatment on mitophagy.

Results: A total of 27 constituents in Qing-Re-Xiao-Zheng-Yi-Qi Formula were tentatively identified. We found PINK1/Parkin-mediated mitophagy was inhibited in diabetic kidney disease. Qing-Re-Xiao-Zheng-Yi-Qi Formula treatment could raise body weight and reduce renal index, reduce proteinuria, improve glycolipid metabolic disorders, ameliorate renal fibrosis, and reduce the expression of Col Ⅳ and TGF-β1 in diabetic kidney disease rats. Qing-Re-Xiao-Zheng-Yi-Qi Formula treatment could also increase the expression of nephrin, activate mitophagy and protect podocytes in diabetic kidney disease rats and high glucose cultured podocytes.

Conclusion: PINK1/Parkin-mediated mitophagy was inhibited in diabetic kidney disease, and Qing-Re-Xiao-Zheng-Yi-Qi Formula treatment could not only ameliorate pathological damage, but also promote mitophagy to protect podocytes in diabetic kidney disease.
Adaptive iterative learning control method for finite-time tracking of an aircraft track angle system based on a neural network
Authors: Zhang Chunli , Tian Xu , Yan Lei
Published: December 2022

Based on a neural network, this paper presents a new adaptive iterative learning control method for the finite-time tracking control problem of an uncertain aircraft track angle system, which can control the aircraft track inclination through the designed control input rudder deflection angle, so that it can track the preset trajectory in a finite time interval. First, the flight path angle system of the aircraft is abstractly modeled by variable substitution to obtain a triangular model in the form of strict feedback. Second, radial basis function neural network approximation is used to model the uncertain part of the system, aiming at the abstract strict feedback model, and two virtual quantities are designed through the three-layer inversion design method, and then, Lyapunov functions are designed for each subsystem to derive virtual control laws, the actual control law, and the neural network weight adaptive laws. Through Lyapunov stability analysis, it can be seen that the designed controller and adaptive laws can make the whole closed-loop system tend to be stable and realize the tracking of a target trajectory in a finite time interval. Finally, the feasibility and effectiveness of the theory are verified by a simulation example.
Complex effects of childhood abuse, subjective social status, and trait anxiety on presenteeism in adult volunteers from the community
Authors: Nibuya Rintaro , Shimura Akiyoshi , Masuya Jiro , Iwata Yoshio , Deguchi Ayaka , Ishii Yoshitaka , Tamada Yu , Fujimura Yota , Tanabe Hajime , Inoue Takeshi
Published: December 2022

Background

Presenteeism, which is reduced productivity levels owing to physical or mental problems, causes substantial economic loss. It is known to be associated with personal and working environment factors, but the mechanism has not been fully clarified to date. Therefore, we analyzed the effects of childhood abuse on presenteeism of general adult workers, and the mediating effects of subjective social status and trait anxiety.

Methods

From 2017 to 2018, a cross-sectional survey was performed, and 469 adult workers provided written consent. Demographic information, and results from the Child Abuse and Trauma Scale, Subjective Social Status, State–Trait Anxiety Inventory form Y, and Work Limitations Questionnaire were investigated. Multiple linear regression and path analyzes were performed.

Results

Childhood abuse indirectly affected current presenteeism via subjective social status and trait anxiety. Presenteeism was directly affected only by trait anxiety, childhood abuse directly affected subjective social status and trait anxiety, and subjective social status affected trait anxiety.

Conclusion

This study clarified the long-term effects of childhood abuse on presenteeism in adulthood via trait anxiety. Therefore, assessing childhood abuse, subjective social status, and trait anxiety may help to elucidate the mechanism of workplace presenteeism and develop measures against it.
Hot spots and frontiers of postpartum depression research in the past 5 years: A bibliometric analysis
Authors: Wang Runfang , Shan Yaokun
Published: December 2022

Objective

This study applied the bibliometric method to analyze the hotspots and frontiers in the field of postpartum depression research from 2017 to 2021.

Methods

A computer-based search for studies related to postpartum depression (PPD) was conducted in the Web of Science Core Collection from 2017 to 2021. Using CiteSpace 5.8. R3 visualization software, this paper analyzed the hot spots and frontiers of postpartum depression research from countries, institutions, authors, cited references and keywords, and drew corresponding knowledge maps.

Results

A total of 3,789 articles were retrieved, and the annual publication volume showed a steady increase. The countries and institutions with the most publications were the United States and the University of Toronto, respectively. Cindylee Dennis was the most productive author. The most frequently cited and centrally cited articles were meta-analyses on risk factors associated with antenatal depression or anxiety and meta-analyses on the prevalence of antenatal or postnatal anxiety, respectively. The research hotspots in the field of postpartum depression in the past 5 years mainly focused on the risk factors for PPD, and the impact of the COVID-19 epidemic on PPD. Providing various aspects of social and family support to women with PPD may be a research trend in this field.

Conclusion

This study provides a trend and frontier in the field of postpartum depression, and valuable information for researchers to find potential partners and partner countries, and a reference for future research topics and development directions.
The effect of incongruous contextual cues on pictorial metaphor processing
Authors: Mo Yongyi , Zhou Rong , Chen Xi
Published: December 2022

An eye-tracking experiment was conducted to investigate the effects of incongruous contextual cues, both perceptual and conceptual, on pictorial metaphor processing. In a metaphoricity decision task, 38 participants independently viewed a total of 36 pictures equally divided into three different conditions: metaphoric pictures (MP), anomalous literal pictures (ALP) with perceptual congruity, and congruous literal pictures (LP). By initiating the midway condition ALP, the effect of contextual cues of conceptual incongruity were distinguished from that of perceptual incongruity. The eye movement data during each picture viewing were collected before the participant made a decision whether the picture was metaphorical or not. The behavioral results showed that the more abundant incongruous contextual cues were there, the more likely the pictures would be judged as metaphors. It took longer for the participants to make decisions on the literal pictures, be them in congruous or incongruous condition. The results of eye-tracking statistics showed that the perceptual incongruity cues were detected earlier than the conceptual ones. The perceptual-conceptual incongruity cues evoked more fixations and longer duration than the perceptual incongruity alone. The processing of conceptual incongruity proceeded after that of perceptual incongruity. The overall result of the study supports the contextual cues of perceptual incongruity as triggers for pictorial metaphor processing, whereas the contextual cues of conceptual incongruity play a decisive role in the metaphoric interpretation, which in turn renders the processing of MP more mental effort consuming than that of ALP or LP. The present findings have vital implications in revealing the triggering and determining mechanisms of pictorial metaphor processing, which are significant in exploring human cognition and have great impacts on various facets of social and cultural communications.
Construction and validation of nomograms combined with novel machine learning algorithms to predict early death of patients with metastatic colorectal cancer
Authors: Zhang Yalong , Zhang Zunni , Wei Liuxiang , Wei Shujing
Published: December 2022

Purpose

The purpose of this study was to investigate the clinical and non-clinical characteristics that may affect the early death rate of patients with metastatic colorectal carcinoma (mCRC) and develop accurate prognostic predictive models for mCRC.

Method

Medical records of 35,639 patients with mCRC diagnosed from 2010 to 2019 were obtained from the SEER database. All the patients were randomly divided into a training cohort and a validation cohort in a ratio of 7:3. X-tile software was utilized to identify the optimal cutoff point for age and tumor size. Univariate and multivariate logistic regression models were used to determine the independent predictors associated with overall early death and cancer-specific early death caused by mCRC. Simultaneously, predictive and dynamic nomograms were constructed. Moreover, logistic regression, random forest, CatBoost, LightGBM, and XGBoost were used to establish machine learning (ML) models. In addition, receiver operating characteristic curves (ROCs) and calibration plots were obtained to estimate the accuracy of the models. Decision curve analysis (DCA) was employed to determine the clinical benefits of ML models.

Results

The optimal cutoff points for age were 58 and 77 years and those for tumor size of 45 and 76. A total of 15 independent risk factors, namely, age, marital status, race, tumor localization, histologic type, grade, N-stage, tumor size, surgery, radiation, chemotherapy, bone metastasis, brain metastasis, liver metastasis, and lung metastasis, were significantly associated with the overall early death rate of patients with mCRC and the cancer-specific early death rate of patients with mCRC, following which nomograms were constructed. The ML models revealed that the random forest model accurately predicted outcomes, followed by logistic regression, CatBoost, XGBoost, and LightGBM models. Compared with other algorithms, the random forest model provided more clinical benefits than other models and can be used to make clinical decisions in overall early death and specific early death caused by mCRC.

Conclusion

ML algorithms combined with nomograms may play an important role in distinguishing early deaths owing to mCRC and potentially help clinicians make clinical decisions and follow-up strategies.
Weighing patient attributes in antibiotic prescribing for upper respiratory tract infections: A discrete choice experiment on primary care physicians in Hubei Province, China
Authors: Xue Tianqin , Liu Chaojie , Li Zhuoxian , Liu Junjie , Tang Yuqing
Published: December 2022

Objectives

This study aimed to determine how primary care physicians weigh intervenable patient attributes in their decisions of antibiotic prescribing for upper respiratory tract infections (URTIs).

Methods

A discrete choice experiment (DCE) was conducted on 386 primary care physicians selected through a stratified cluster sampling strategy in Hubei province, China. The patient attributes tested in the DCE were identified through semi-structured interviews with 13 primary care physicians, while the choice scenarios were determined by a D-efficient design with a zero prior parameter value. Conditional logit models (CL) and mixed logit models (MXL) were established to determine the preference of the study participants in antibiotic prescribing for URTI patients with various attributes. Relative importance (RI) was calculated to reflect the influence of each attribute.

Results

In addition to age and duration of symptoms, the interventionable patient attributes were also considered by the primary care physicians in their antibiotic prescribing decisions. They preferred to prescribe antibiotics for URTI patients with difficulties to schedule a follow-up appointment (p < 0.001) and for those without a clear indication of refusal to antibiotics (p < 0.001). Patient request for antibiotics had an RI ranging from 15.2 to 16.3%, compared with 5.1–5.4% for easiness of follow-up appointment. The influence of these two interventionable patient attributes was most profound in the antibiotic prescribing decisions for patients aged between 60 and 75 years as indicated by their interaction effects with age (β = 0.69 for request for antibiotics, p < 0.01; β = −1.2 for easiness of follow-up, p < 0.001).

Conclusion

Reducing patient pressure and improving accessibility and continuity of care may help primary care physicians make rational antibiotic prescribing decisions for URTIs.
Qualities of transformative leaders in WASH: A study of gender-transformative leadership during the COVID-19 pandemic
Authors: Gonzalez Diana , Carrard Naomi , Chhetri Aastha , Somphongbouthakanh Phetsakhone , Choden Tshering , Halcrow Gabrielle , Budhathoki Ratan , Wangchuk Ugyen , Willetts Juliet
Published: December 2022

Introduction

Equal access to water, sanitation and hygiene (WASH) for all requires leadership that prioritises and drives inclusion. Inclusive WASH also presents opportunities to advance equality more widely, with WASH a pathway to meaningful participation and empowerment for diverse groups. The concept of gender-transformative leadership-which connects ideas of leadership to transformative models of gender equality in development theory that challenge prevailing power structures-is a relevant lens for exploring inclusive WASH. This article shares findings and reflections from a positive deviance study that aimed to investigate gender-transformative leadership in the WASH sector to explore (i) the factors shaping gender-transformative leadership and the characteristics of gender-transformative leaders; (ii) actions taken by gender-transformative leaders; (iii) the types of outcomes achieved; and (iv) ways to strengthen gender-transformative leadership.

Methods

The study was undertaken during the COVID-19 pandemic and consisted of interviews with 19 leaders in Bhutan, Lao People's Democratic Republic, and Nepal. We developed a conceptual framework which considers leaders' (i) personal values and traits; (ii) leadership styles; (iii) actions; and (iv) outcomes, influenced by a range of (v) enabling factors and barriers.

Results

Leaders' personal values and traits included a strong learning orientation, social justice values, humility, courage, and altruism. Leadership styles were primarily empathetic, with leaders guided by a mission to lead by example and pursue equality in their professional and personal lives. Exploration of actions and outcomes revealed a range of inclusion-oriented WASH activities responding to pandemic-related challenges, with associated potential outcomes in shifting norms. However, validation of outcomes was not possible due to the study timeframe and complexity of tracing complex social change in a positive deviance study reliant on self-reporting. Analysis of enablers and barriers to gender-transformative leadership respectively emphasized the importance of educational opportunities and the persistence of traditional gender norms.

Conclusion

Findings contribute to the body of knowledge on gender-transformative leadership, being the first study to connect this concept to WASH. Future research could build further evidence by applying the conceptual framework to analyze additional contexts or sectors, and by more fully articulating and validating outcomes in terms of their potential for gender-transformative leadership to drive equality both in and beyond WASH.
MAFIAT: Magnetic field analysis tools
Authors: Price D. J. , Pomoell J. , Kilpua E. K. J.
Published: December 2022

The magnetic twist is one of the key defining parameters of solar flux ropes (FRs). The routine computation of the winding of magnetic field lines, referred to as the twist, has the potential to lead to significant advancement in the field of solar physics and solar—terrestrial research, e.g., by enabling more accurate investigations of FR morphology, stability, and temporal evolution. However, this has been hampered by the axial-dependence of the solution and the availability of simpler, albeit approximate, methods. Here we introduce the Magnetic Field Analysis Tools (MAFIAT) python library and Jupyter notebooks for the computation and exploitation of this quantity. The required axis location is specified manually by the user, either with their own preferred method, or using the twist number calculated from the parallel current by Magnetic Field Analysis Tools. The notebooks allow users to create a variety of novel visualisations of FRs and their twist distributions for scientific study. Magnetic Field Analysis Tools is written in Python and is released under the BSD 3-Clause Licence. Code available at: https://github.com/pricedj/mafiat.
Intrahepatic eosinophilic proliferative phlebitis in Japanese black cattle indicate allergies involving mast cell tryptase-dependent activation
Authors: Konnai Masaki , Takahashi Kimimasa , Machida Yukino , Michishita Masaki , Ohkusu-Tsukada Kozo
Published: December 2022

Cow-specific feature hepatic lesion, termed as eosinophilic proliferative phlebitis (EPP), has been mainly detected in Japanese black cattle and identified histologically eosinophilic infiltration and endothelial hyperplasia in portal areas. We previously proposed EPP as a food allergy from the pathological characteristics and a significant increase of serum immunoglobulin E specific to curly dock (Rumex crispus) in allergens testing, however, first report had regarded EPP an atypical type of bovine fascioliasis. In EPP lesions, eosinophilic infiltration was observed to the hypertrophic endothelium and not to the intrahepatic bile duct, and that was related to eotaxin-1 expression. In EPP, the mast cells increased as well as in fascioliasis, and the mast cells producing tryptase without chymase increased with interleukin-4 production. In this context, hyperplasia of periendothelium expressing proteinase-activated receptor-2 (PAR-2) and not angiotensin II was observed. Contrastably, in fascioliasis, unique mast cells producing neither tryptase nor chymase infiltrated, and the periendothelium expressed neither PAR-2 nor angiotensin II. Interestingly, EPP had not occurred liver injury with raised hepatic enzymes like fascioliasis, and suggested to a correlation with severe serum hypo-vitamin A. Overall, this study suggests that EPP is an allergic disease by main difference between adaptive immunity to allergens and innate immunity to parasites.
Microforce Sensing and Flexible Assembly Method for Key Parts of ICF Microtargets
Authors: Chen Tao , Ni Kejian , Zhu Minglu , Sun Lining
Published: December 2022

Microassembly is one of the key techniques in various advanced industrial applications. Meanwhile, high success rates for axial hole assembly of thin-walled deep-cavity-type items remain a challenging issue. Hence, the flexible assembly approach of thin-walled deep-cavity parts is investigated in this study using the assembly of the key components, the microtarget component TMP (thermomechanical package) and the hohlraum in ICF (inertial confinement fusion) research, as examples. A clamping force-assembly force mapping model based on multisource microforce sensors was developed to overcome the incapacity of microscopic vision to properly identify the condition of components after contact. The ICF microtarget flexible assembly system, which integrates multisource microforce sensing and a six degrees of freedom micromotion sliding table, is presented to address the constraint that the standard microassembly approach is difficult to operate once the parts contact. This method can detect contact force down to the mN level, modify deviation of the component posture efficiently, and achieve nondestructive ICF microtarget assembly at the end.
COSUTI: A Core Outcome Set (COS) for Interventions for the Treatment of Uncomplicated Urinary Tract Infection (UTI) in Adults
Authors: Beecher Claire , Duane Sinead , Vellinga Akke , Murphy Andrew W. , Cormican Martin , Smyth Andrew , Healy Patricia , Moore Michael , Little Paul , Geoghegan Carmel , Devane Declan
Published: December 2022

Background: Uncomplicated urinary tract infections (UTIs) are among the most common presentations of bacterial infections in the outpatient setting. The variation of outcomes reported in trials to assess the most effective treatment interventions for uncomplicated UTIs has meant that comparing and synthesising the outcomes across trials is challenging and limits the reliability of evidence which would otherwise inform healthcare decisions. Objective: Develop a Core Outcome Set (COS) for interventions for the treatment of uncomplicated UTIs in otherwise healthy adults. Methods: The COS development consisted of three phases: (1) A systematic review to identify outcomes reported in randomised trials and systematic reviews of randomised trials comparing the effectiveness of any interventions for the treatment of uncomplicated UTI in otherwise healthy adults; (2) Outcomes identified in the systematic review were prioritised in an online 3-round modified Delphi survey with healthcare practitioners (n = 68), researchers (n = 5), and people who have experienced or cared for someone experiencing a UTI (n = 180); (3) An online consensus meeting to determine the final COS with healthcare practitioners and policymakers (n = 9), researchers (n = 4), and people who have experienced or cared for someone experiencing a UTI (n = 7). Results: We identified a large number of outcomes. Through the use of robust consensus methods, those outcomes were reduced to a core set of six outcomes that should, at a minimum, be measured and reported in randomised trials and systematic reviews of interventions treating uncomplicated UTIs in adults.
Operational Stability Analysis of Blue Thermally Activated Delayed Fluorescence Organic Light-Emitting Diodes Using the Capacitance-Voltage Method
Authors: Park Jun-Young , Park Soo-Jong , Ju Byeong-Kwon
Published: December 2022

We analyzed the degradation features by measuring the capacitance–voltage characteristics after electrically aging blue thermally activated delayed fluorescence (TADF) organic light-emitting diodes (OLEDs). The measurement was investigated in terms of the hole transfer layer (HTL) and electron transfer layer (ETL) structures. For the HTL, three different materials—N,N′–bis(naphthalen–1–yl)–N,N′–bis(phenyl)–benzidine (NPB), 4,4′,4″-tris(carbazol–9–yl)triphenylamine (TCTA), and 1,3–bis(carbazol–9–yl)benzene (mCP)—were used at the HTL/emission layer (EML) interface; the TCTA/EML interface had the highest stability among the interfaces. For the ETL, bis [2–(diphenylphosphino)phenyl] ether oxide (DPEPO) without further dopants was used as an exciton blocking layer (ExBL) to effectively confine the excitons at the EML. However, DPEPO has low stability and carrier mobility. Therefore, 0, 10, and 40 nm-thick ExBL devices were investigated; it was found that the 0 nm-thick ExBL device was the most stable. However, the 10 nm-thick ExBL is essential to confine the excitons at the EML, which ensures a high EL performance.
Mechanical Characteristics of Pre-Peak Unloading Damage and Mechanisms of Reloading Failure in Red Sandstone
Authors: Zhu Yongjian , Li Peng , Wang Ping , Mei Chengcheng , Ren Heng , Wang Xizhi
Published: December 2022

The mining of deep coal resources occurs in a high-stress geological environment as well as an engineering environment of rock excavation and unloading. Research on the re-bearing capacity characteristics and damage mechanism of rock masses damaged by peak front unloading is critical in revealing the destabilization and rupture law of deep rock bodies. The triaxial pre-peak unloading point was controlled to prepare damaged sandstone specimens, and the RMT-150C rock mechanics test loading system and the AEwin USB-type acoustic emission monitor were used to perform uniaxial reloading tests on the pre-peak unloading-damaged sandstone and to monitor the acoustic emission signals during the rupture process. Among them, the peak front unloading point was set to 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, and 90% of the peak strength at 10 MPa of the surrounding pressure for a total of 11 working conditions. The test results show that: (1) The degree of unloading before the peak controls the uniaxial reload deformation characteristics of sandstone. The higher the unloading point, the faster the deformation of the rock sample, even directly into the crack instability extension stage, and the sandstone deformation characteristics transform from plastic—elastic to elastic—viscous. (2) The cumulative energy characteristics of the 40% to 60% sandstone at the unloading point are comparable to those of the complete sandstone and are separated into smooth, steady growth, and secondary smooth phases. The acoustic emission energy characteristics of the 65% and 70% sandstone at the unloading point are mostly focused on during the crack expansion stage. The sandstone’s acoustic emission energy characteristics exhibit a “double peak” occurrence at 75% of the unloading point. The cumulative energy characteristics of the 80% to 90% sandstone at the unloading point reveal a “stepped” rise. (3) Sandstone’s pre-peak unloading rupture morphology influences the reload damage characteristics: 40% to 70% of the specimens at the unloading point exhibit “Y”-type double-slope shear damage features. The predominant cause of specimen damage in 75% of the specimens at the unloading point is secondary primary cracks based on the pre-peak tensile rupture pattern. The damage path of 80% to 90% of the specimens at the point of unloading occurs in shear damage along the pre-peak unloading rupture pattern. (4) A closed crack mechanics analysis model under uniaxial reload was established, and the basic solution of pseudo-force for fine microcracks subjected to far-field stress, the stress intensity factor at the crack tip, and the crack fracture angle were theoretically derived. Furthermore, the relationship between the fracture angle θ of rock compression-shear cracks, the crack angle β, and the friction coefficient f at the crack surface was clarified.
Determination of Calorific Value of Mixed Coals by Analysis of Major Elements Using Data Pre-Processing in Laser-Induced Breakdown Spectroscopy
Authors: Park Jong Hyun , Ryu Choong Mo , Park Kyung Hoon , Choi Jung Hyun , Moon Seung Jae
Published: December 2022

The purpose of this study was to enhance the accuracy of the calorific value estimation of coal by applying data preprocessing methods in laser-induced breakdown spectroscopy (LIBS). The Savitzky–Golay (SG)-smoothing and SG derivative preprocessing methods were adopted to improve the accuracy of the prediction model. The relationship among the original, SG-smoothing-pretreated, and SG derivative-pretreated LIBS data and their elemental concentrations were determined using the partial least squares regression (PLSR) model. In order to compare the reliability of each PLSR model, the coefficient of determination, root mean square error (RMSE), relative error, and RMSE average were used. As a result, the reliability of the PLSR model processed with the SG derivative method was the highest, and the root mean square average was the lowest among the three models. The predictability of the concentration of each element using the PLSR model pre-processed by the SG derivative was confirmed with the residual predictive deviation parameter. The predicted calorific value was estimated from the predicted concentrations of elements in coal using Dulong’s equation. The PLSR model pretreated by the SG derivative showed the lowest error compared to the calorific value of mixed coals obtained via the chemical analysis.
Up and Down h-Pre-Invex Fuzzy-Number Valued Mappings and Some Certain Fuzzy Integral Inequalities
Authors: Khan Muhammad Bilal , Zaini Hatim Ghazi , Macías-Díaz Jorge E. , Soliman Mohamed S.
Published: December 2022

The objective of the current paper is to incorporate the new class and concepts of convexity and Hermite–Hadamard inequality with the fuzzy Riemann integral operators because almost all classical single-valued and interval-valued convex functions are special cases of fuzzy-number valued convex mappings. Therefore, a new class of nonconvex mapping in the fuzzy environment has been defined; up and down h-pre-invex fuzzy-number valued mappings (U.D h-pre-invex F-N∙V∙Ms). With the help of this newly defined class, some new versions of Hermite–Hadamard (HH) type inequalities have been also presented. Moreover, some related inequalities such as HH Fejér- and Pachpatte-type inequalities for U∙D h-pre-invex F-N∙V∙Ms are also introduced. Some exceptional cases have been discussed, which can be seen as applications of the main results. We have provided some nontrivial examples. Finally, we also discuss some future scopes.
Diversity of Biogenic Nanoparticles Obtained by the Fungi-Mediated Synthesis: A Review
Authors: Loshchinina Ekaterina A. , Vetchinkina Elena P. , Kupryashina Maria A.
Published: December 2022

Fungi are very promising biological objects for the green synthesis of nanoparticles. Biogenic synthesis of nanoparticles using different mycological cultures and substances obtained from them is a promising, easy and environmentally friendly method. By varying the synthesis conditions, the same culture can be used to produce nanoparticles with different sizes, shapes, stability in colloids and, therefore, different biological activity. Fungi are capable of producing a wide range of biologically active compounds and have a powerful enzymatic system that allows them to form nanoparticles of various chemical elements. This review attempts to summarize and provide a comparative analysis of the currently accumulated data, including, among others, our research group’s works, on the variety of the characteristics of the nanoparticles produced by various fungal species, their mycelium, fruiting bodies, extracts and purified fungal metabolites.
Rewiring Lipid Metabolism by Targeting PCSK9 and HMGCR to Treat Liver Cancer
Authors: Alannan Malak , Trézéguet Véronique , Amoêdo Nivea Dias , Rossignol Rodrigue , Mahfouf Walid , Rezvani Hamid Reza , Dittrich-Domergue Franziska , Moreau Patrick , Lacomme Sabrina , Gontier Etienne , Grosset Christophe F. , Badran Bassam , Fayyad-Kazan Hussein , Merched Aksam J.
Published: December 2022

Alterations in lipid handling are an important hallmark in cancer. Our aim here is to target key metabolic enzymes to reshape the oncogenic lipid metabolism triggering irreversible cell breakdown. We targeted the key metabolic player proprotein convertase subtilisin/kexin type 9 (PCSK9) using a pharmacological inhibitor (R-IMPP) alone or in combination with 3-hydroxy 3-methylglutaryl-Coenzyme A reductase (HMGCR) inhibitor, simvastatin. We assessed the effect of these treatments using 3 hepatoma cell lines, Huh6, Huh7 and HepG2 and a tumor xenograft in chicken choriorallantoic membrane (CAM) model. PCSK9 deficiency led to dose-dependent inhibition of cell proliferation in all cell lines and a decrease in cell migration. Co-treatment with simvastatin presented synergetic anti-proliferative effects. At the metabolic level, mitochondrial respiration assays as well as the assessment of glucose and glutamine consumption showed higher metabolic adaptability and surge in the absence of PCSK9. Enhanced lipid uptake and biogenesis led to excessive accumulation of intracellular lipid droplets as revealed by electron microscopy and metabolic tracing. Using xenograft experiments in CAM model, we further demonstrated the effect of anti-PCSK9 treatment in reducing tumor aggressiveness. Targeting PCSK9 alone or in combination with statins deserves to be considered as a new therapeutic option in liver cancer clinical applications.
RGD_PLGA Nanoparticles with Docetaxel: A Route for Improving Drug Efficiency and Reducing Toxicity in Breast Cancer Treatment
Authors: Di Gregorio Enza , Romiti Chiara , Di Lorenzo Antonino , Cavallo Federica , Ferrauto Giuseppe , Conti Laura
Published: December 2022

Breast cancer is the leading cause of cancer-related death in women. Although many therapeutic approaches are available, systemic chemotherapy remains the primary choice, especially for triple-negative and advanced breast cancers. Unfortunately, systemic chemotherapy causes serious side effects and requires high doses to achieve an effective concentration in the tumor. Thus, the use of nanosystems for drug delivery may overcome these limitations. Herein, we formulated Poly (lactic-co-glycolic acid) nanoparticles (PLGA-NPs) containing Docetaxel, a fluorescent probe, and a magnetic resonance imaging (MRI) probe. The cyclic RGD tripeptide was linked to the PLGA surface to actively target αvβ3 integrins, which are overexpressed in breast cancer. PLGA-NPs were characterized using dynamic light scattering, fast field-cycling 1H-relaxometry, and 1H-nuclear magnetic resonance. Their therapeutic effects were assessed both in vitro in triple-negative and HER2+ breast cancer cells, and in vivo in murine models. In vivo MRI and inductively coupled plasma mass spectrometry of excised tumors revealed a stronger accumulation of PLGA-NPs in the RGD_PLGA group. Targeted PLGAs have improved therapeutic efficacy and strongly reduced cardiac side effects compared to free Docetaxel. In conclusion, RGD-PLGA is a promising system for breast cancer treatment, with positive outcome in terms of therapeutic efficiency and reduction in side effects.
Estimation of Excitation Current of a Synchronous Machine Using Machine Learning Methods
Authors: Glučina Matko , Anđelić Nikola , Lorencin Ivan , Car Zlatan
Published: December 2022

A synchronous machine is an electro-mechanical converter consisting of a stator and a rotor. The stator is the stationary part of a synchronous machine that is made of phase-shifted armature windings in which voltage is generated and the rotor is the rotating part made using permanent magnets or electromagnets. The excitation current is a significant parameter of the synchronous machine, and it is of immense importance to continuously monitor possible value changes to ensure the smooth and high-quality operation of the synchronous machine itself. The purpose of this paper is to estimate the excitation current on a publicly available dataset, using the following input parameters: Iy: load current; PF: power factor; e: power factor error; and df: changing of excitation current of synchronous machine, using artificial intelligence algorithms. The algorithms used in this research were: k-nearest neighbors, linear, random forest, ridge, stochastic gradient descent, support vector regressor, multi-layer perceptron, and extreme gradient boost regressor, where the worst result was elasticnet, with R2 = −0.0001, MSE = 0.0297, and MAPE = 0.1442; the best results were provided by extreme boosting regressor, with R2¯ = 0.9963, MSE¯ = 0.0001, and MAPE¯ = 0.0057, respectively.
Methodology to Reach Full Spectral Photo-Protection by Selecting the Best Combination of Physical Filters and Antioxidants
Authors: Lan Alexandra , Lui Yan , Zuo Jinhui , Lohan Silke B. , Schanzer Sabine , Wiemann Sabrina , Keck Cornelia M. , Lademann Jürgen , Meinke Martina C.
Published: December 2022

Antioxidants can reduce free radical formation in deeper skin layers where typical sunscreen filters may no longer be effective. Here, a general method is presented to pre-select optimum combinations of antioxidants and physical filters. The radical production of selected common physical filters after UV irradiation, the capacity of different antioxidants and the interaction between these compounds was investigated in solution by optical measurement of DPPH scavenging, allowing a theoretical calculation of the antioxidant amount necessary to scavenge UV-induced radicals. Furthermore, the antioxidant capacity and the scattering properties were determined. All physical filters induced different amounts of radicals in suspensions depending on the coating. ZnO coated with polydimethylsiloxane and myristic acid (ZnOpolymyr) showed the lowest radical formation. Epigallocatechin-gallate (EGCG) provided the highest antioxidant capacity. Different formulations with different ratios of selected physical filters and antioxidants were prepared. It turned out that the high radical protection factor (RPF) of cream formulations, which originally did not contain any physical filters, was reduced when such filters were added. The data demonstrates that the addition of physical filters to antioxidant-containing formulations lowers their reduction capacity, but to varying degrees. An optimal combination of physical filters and antioxidants must be pre-selected in order to incorporate them into a formulation and verify their effect on skin.
Exploring the Feasibility of Mitigating Flood Hazards by an Existing Pond System in Taoyuan, Taiwan
Authors: Tseng Kuo-Hsin , Yang Tsun-Hua , Chen Pei-Yuan , Chien Hwa , Chen Chi-Farn , Hung Yi-Chan
Published: December 2022

Changes in the global climate have induced densified rainfall and caused natural hazards across the world in recent years. Formed by a central mountain range and a corridor of alluvial plains to the west, Taiwan is at risk of flood hazards owing to its low-lying lands as well as the distinct seasonality of rainfall patterns. The rapid discharge of surface runoff and a growing number of impervious surfaces have also increased flood hazards during recent typhoon landfalls. A century ago, ancestors in Taoyuan City constructed a system of water channels composed of thousands of ponds to fulfill the needs of agriculture and aquaculture. During the expansion of urban areas, land reformation replaced a majority of earlier ponds with residential and industrial zones. However, the remaining ponds could potentially serve as on-site water detention facilities under the increasing risk of floods. In this research, we first renewed an outdated pond database by deploying a novel unmanned aerial vehicle (UAV) system with a micro-sonar to map the bathymetry of 80 ponds. Next, a simplified inundation model (SPM) was used to simulate the flood extent caused by different scenarios of rainfall in Bade District of Taoyuan City. Assuming that extremely that heavy rainfalls at 25, 50, 75, and 100 mm occurred in a very short period, the flood area would decrease by 96%, 75%, 52%, and 37%, respectively, when the ponds were preparatorily emptied.