bluuebunny/crossref_metadata_2025 huggingface dataset:
Data Analytics Software for Automatic Detection of Anomalies in Well Testing
Authors: Capponi Stefano , Nwachukwu Chiazor
Published: September 2021

This paper will present a software that was developed to diagnose well test data. The software monitors the data, and through a series of algorithms alarms the user in case of discrepancies. This allows the user to investigate possible source of errors and correct them in real time.

Several datasets from previous operations were analyzed and the basic physics governing how a certain datum depends on others were laid out. All the well test data traditionally acquired were put on a matrix, showing the dependencies between each datum and other physical properties that are available - either measured or modelled. Acceptable fluctuations in acquired data were also identified for use as tolerance limits. The software scans through the data as it is acquired and raises an alarm when the identified dependencies are broken. The software also identified which parameter is most likely causing the error.

The software was built based on previous well test data and reports. Subsequently, two field trials were conducted to fine tune the algorithms and allowable data fluctuations. The process of validating the software consisted of: (1) Identifying flagged errors that should have not been flagged (dependencies set too tight); (2) identifying errors that should have been flagged and were not (dependencies set too loose); (3) improving the user interface for ease of use. The results were positive, with several improvements in the error recognition and several discrepancies flagged that would not have been caught by the naked eye. The user interface was also improved, allowing the user to clear error messages and provide input to improve the algorithm. The field trial also demonstrated that the methodology is scalable to other data acquisition plans and to more advanced analytics. The algorithms are simple, allowing the software to be implemented in all operations. More advanced algorithms are likely to depend on job specific data and parameters.

Traditional data acquisition systems used during well test only present the data. Alarms trigger the user's attention only when certain defined operability limits are about to be reached. Being able to confirm that the data is cohesive during the well test prevents a loss of confidence in the results and painful post processing exercises. Moreover, given the algorithms used are based on simple physics, it is easy to deploy the software in any operation.
Protective effect of Bmscs-derived exosomes on testicular ischemia-reperfusion injury in rats
Authors: Tian Hu , Zhang Wan-song , Yang Cheng , Zhou Jun-hao , Zhou Ran-ran , Guo Wen-bin , Liu cundong
Published: September 2021

Background

Testicular Ischemia reperfusion injury(IRI) is a major pathophysiological process of surgical reduction after testicular torsion, and oxidative stress is the main injury factor. However, the role of BMSCs-derived exosomes in testicular IRI and its mechanism have not been reported. In this study, we investigated the protective effect of bone marrow mesenchymal stem cell-derived exosomes against testicular ischemia-reperfusion injury.
Methods

Results: BMSCs were successfully isolated and cultured from rat bone marrow, and exosomes secreted by BMSCs were successfully extracted. In vivo experiment: The testicular torsion rat model was established, and various biochemical indexes of oxidative stress and testicular tissue HE was detected in the sham operation group, testicular torsion group and bone marrow mesenchymal stem cell-derived exosome treatment group. In vitro experiment: H2O2 was used to construct TM4 and GC1 oxidative stress models, and various biochemical indexes of oxidative stress and corresponding pathway proteins were detected in the control group, H2O2 group and bone marrow mesenchymal stem cell-derived exosome treatment group.
Conclusion

BMSCs-derived exosomes can be absorbed by rat spermatogonia and have antioxidant and anti-inflammatory protective effects against testicular ischemia-reperfusion injury。
Efficacy and Safety of Rhomboid Intercostal Block for Analgesia in Breast Surgery and Thoracoscopic Surgery: A Meta-Analysis
Authors: Chen Ruirong , Su Sheng , Shu Haihua
Published: September 2021

BackgroundRhomboid intercostal block (RIB) is a new regional anesthesia technique that provides postoperative analgesia for breast surgery and thoracoscopic surgery. The published papers are not yet fully integrated and do not adequately address the impact and safety of the RIB on postoperative pain.MethodsThe PubMed, Web of Science and Embase were searched from 2016 to 2021 for all available randomized controlled trials (RCTs) that evaluated the analgesic efficacy and safety of RIB after thoracic surgery and breast surgery. Random and fixed-effects meta-analytical models were used where indicated, and between-study heterogeneity was assessed. The primary outcome was Postoperative Numerical Rating Scale (NRS) scores of patients at rest recorded 0-1, 6-8, 24 hours after surgery. The secondary outcomes included rate of postoperative nausea and vomiting (PONV), postoperative fentanyl consumption and presence of complications of the block. ResultsFrom 81 records identified, four studies met our inclusion criteria, including 216 patients (RIB:108 patients; no block: 108 patients). In the primary outcome, RIB group showed significantly lower postoperative NRS at rest at first 0-1 h and 6-8 h (weighted mean difference [WMD] = -1.55; 95% confidence internal [CI] = -2.92 to -0.19; p<0.05), (WMD = -0. 69; 95% CI = -1.29 to -0. 09; p<0. 05). And there was no significant difference between groups in NRS at rest at 24 h (WMD = -0.78; 95% CI = -1.64 to -0.08; p=0.77). Also, RIB group showed significantly lower postoperative NRS of breast surgery and thoracoscopic surgery at 0-1h (WMD = -3.00; 95% CI = -3.13 to -2.87; p<0.01), (WMD = -1.08; 95% CI = -1.98 to -0.18; p<0.05). In the secondary outcome, the analysis also showed RIB group had significant lower of POVN rates (summary relative risk (RR) = 0.212;95%CI = 0.10 to 0.45; p<0. 01) and the postoperative consumption of fentanyl (WMD= -57.52;95%CI = -106.03 to -9.02; p<0. 05). ConclusionThis review shows that RIB was more effective in controlling acute pain after breast surgery and thoracoscopic surgery than general analgesia. And RIB is also a kind of effective and safe bock technology.
The Potential of Invasive and Non-Invasive Vagus Nerve Stimulation To Improve Verbal Memory Performance in Epilepsy Patients
Authors: Mertens Ann , Gadeyne Stefanie , Lescrauwaet Emma , Carrette Evelien , Meurs Alfred , De Herdt Veerle , Dewaele Frank , Raedt Robrecht , Miatton Marijke , Boon Paul , Vonck Kristl
Published: September 2021

Introduction:
It has been demonstrated that acute vagus nerve stimulation (VNS) improves word recognition memory in epilepsy patients. Transcutaneous auricular vagus nerve stimulation (taVNS) has gained interest as a non-invasive alternative to improve cognition. In this prospective randomized cross-over study, we investigated the effect of both invasive VNS and taVNS on verbal memory performance in 15 drug-resistant epilepsy patients.
Methods
All patients conducted a word recognition memory paradigm in 3 conditions: VNS ON, VNS OFF and taVNS. For each condition, patients memorized 21 highlighted words from text paragraphs. Afterwards, the intervention was delivered for 30 s. Immediate recall and delayed recognition scores were obtained for each condition. This memory paradigm was repeated after 6 weeks of VNS therapy in 2 conditions: VNS ON and VNS OFF.
Results
Acute VNS and taVNS did not improve verbal memory performance. Immediate recall and delayed recognition scores were significantly improved after 6 weeks of VNS treatment irrespective of the acute intervention.
Conclusion
The previously described positive effects of invasive VNS on verbal memory performance could not be replicated with invasive VNS and taVNS. An improved verbal memory performance was seen after 6 weeks of VNS treatment, suggesting that longer and more repetitive stimulation of the vagal pathway is required to modulate verbal memory performance.
Growth, Crystal Structure, Hirshfeld Surface Analysis, DFT Studies, Physicochemical Characterization And Cytotoxicity Assays of Novel Organic Triphosphate
Authors: Oueslati Yathreb , Kansız Sevgi , Dege Necmi , Paredes Cristina de la Torre , Lorente Antoni Llopis , Martínez-Máñez Ramón , sta wajda
Published: September 2021

A novel interesting organic-inorganic hybrid compound, named (1-phenylpiperazinium) trihydrogen triphosphate, with the formula (C10H15N2)2H3P3O10 has been obtained by low speed of evaporation at room temperature after using the ion exchange chemical procedure. To carry out a detailed crystallographic structure analysis, single-crystal X-ray diffraction has been reported. In the molecular arrangement, the different entities are held together through N-H…O, O-H…O and C-H…O hydrogen bonds, building up a three dimensional packing. Powder X-ray diffraction analysis is acquired to confirm the purity of the product. The nature and the proportion of intermolecular interactions were investigated by Hirshfeld surfaces analysis. In order to support the experimental results, a density functional theory (DFT) calculation were performed, using the Becke-3-Parameter-Lee-Yang-Parr (B3LYP) function with LANL2DZ basis set, and the data indicate the much agreement between the experimental and the theoretical results. Thus, the physicochemical properties were studied employing a variety of techniques (FT-IR, NMR, UV-Visible and photoluminescence). To get an insight of the possible employment of the present material in biology, cell viability assays were performed.
Durability And Life Prediction of Fly Ash Geopolymer Concrete In Corrosion Environments Caused By Dry And Wet Circulation
Authors: Sun Qi , Li Botao , Wang Yiting , Wang Hui
Published: September 2021

The use of tailings, waste rock, fly ash and slag to prepare geopolymer concrete can effectively solve the problems of land resources occupied by tailings and waste rock, low utilization rate and environmental pollution. Using a dry-wet circulation method, fly ash for a different corrosion solution to geopolymer concrete (referred to as TWGPC) was analysed. Through an appearance change, the corrosion resistance coefficient of the compressive strength, relative dynamic elastic modulus, tensile splitting strength, relative mass and durability were investigated, using scanning electron microscopy (SEM) analysis of the microstructure, The life of TWGPC was predicted based on the GM(1,1) prediction model of grey system theory. The test results show that with an increase in the number of dry-wet cycles, the surface of the specimen crystallizes, cracks, spalls and exhibits other phenomena. The compressive strength corrosion coefficient, relative dynamic elastic modulus, crack tensile strength and relative mass show a trend of increasing first and then decreasing, finally reaching the peak value after 40 cycles. The erosion products generated by the early reaction fill the slurry aggregate pores and improve the strength of TWGPC. In a later stage, a large number of erosion products absorb water and expand, the internal pores of TWGPC are connected, leading to a decrease in strength. Cl- inhibits the corrosion of SO42- in concrete and improves the durability of concrete.
Extranodal Natural Killer/t-cell Lymphoma Nasal Type With Extensive Ocular Tissue Involvement: A Case Report
Authors: Han Ruoan , Jiang Yang , Bian Ailing , Ye Junjie
Published: September 2021

BackgroundTo report a rare case of extranodal natural killer/T-cell lymphoma (ENKTL), nasal type related to extensive ocular tissue, including conjunctiva, ciliary body, vitreous and retina. Case presentationA 52-year-old woman who had been treated by radiotherapy for ENKTL, nasal type in the right nasal cavity presented with a dramatic deterioration of vision in right eye. Physical and accessary examination showed extensive ocular tissue related, including conjunctiva, ciliary body, vitreous and retina. Vitreous specimen and conjunctiva biopsy revealed the presence of ENKTL, nasal type in the right eye. She was treated with systemic and ophthalmic chemotherapy, her ocular symptoms significantly improved, and systemic condition remained stable 7 months after the diagnosis.ConclusionsExtranodal natural killer/T-cell lymphoma, nasal type is an aggressive disease and may relate extensive ocular tissue and course dramatic vision deterioration. It is important to observe ocular related and begin aggressive combined therapy as early as possible after diagnosis.
Increasing Motor Cortex Activation During Grasping Via Novel Robotic Mirror Hand Therapy: A Pilot fNIRS Study
Authors: Kim Dong Hyun , Lee Kun-Do , Bulea Thomas C , Park Hyung-Soon
Published: September 2021

Background: Mirror therapy (MT) has been used for functional recovery of the affected hand by providing the mirrored image of the unaffected hand movement, which induces neural activation of the contralateral cortical hemisphere. Recently, many wearable robots assisting the movement of the hand have been developed, and several studies have proposed robotic mirror therapy (RMT) that provides mirrored movements of the unaffected hand on the affected hand with the robot controlled by electromyography or posture of the unaffected hand. There have been limited evaluations of the cortical activity during RMT compared to MT and robotic therapy (RT) providing passive movements despite the difference in the modality of sensory feedback and the involvement of motor intention, respectively. Methods: This paper analyzes bilateral motor cortex activation in nine healthy subjects and five chronic stroke survivors during a pinching task performed in MT, RT, and RMT conditions using functional near infrared spectroscopy (fNIRS). In the MT condition, the person moved the unaffected hand and observed it in a mirror while the affected hand remained still. In RT condition passive movements were provided to the affected hand with a cable-driven soft robotic glove, while, in RMT condition, the posture of the unaffected hand was measured by a sensing glove and the soft robotic glove mirrored its movement on the affected hand. Results: For both groups, the RMT condition showed the greatest mean cortical activation on the contralateral motor cortex compared to other conditions. Individual results indicate that RMT induces similar or greater neural activation on the motor cortex compared to MT and RT conditions. The interhemispheric activations of both groups were balanced in RMT condition. In MT condition, significantly greater activation was shown on the ipsilateral side for both subject groups, while the contralateral side showed significantly greater activation for healthy in RT condition. Conclusion: The experimental results indicate that combining visual feedback, somatosensory feedback, and motor intention are important for greater stimulation on the contralateral motor cortex of the affected hand. RMT that includes these factors is hypothesized to achieve a more effective functional rehabilitation due to greater and more balanced cortical activation.
Controling Switching between Birhythmic States in a New Conductance-based Bursting Neuronal Model
Authors: NKOUNGA Innocent TAGNE , KAKMENI Francois Marie MOUKAM , CAMARA Baba Issa , YAMAPI R.
Published: September 2021

A birhythmic conductance-based neuronal model with fast and slow variables is proposed to generate and control the coexistence of two different attracting modes in amplitudes and frequencies. However, periodic bursting, chaotic spiking and bursting haven’t been clearly observed there. The control of bistability is investigated in a three-dimensional birhythmic conductance-based neuronal model. We consider slow processes in neuron materialized by an adaptation variable coupled to system in the presence of an externalinusoidal current applied. By using the harmonic balance method, we obtain the frequency-response curve in which membrane potential resonance with his corresponding frequency are control by varying a specific parameter. At the resonance frequency, bifurcation and lyapunov exponent diagrams versus a control parameter are obtained. They reveal, a coexistence of two different complex attractors namely periodic and chaotic spiking, periodic and chaotic bursting. By using the control parameter as the slow variable, the system can switch from bistable to monostable behavior. This is done by destroying subthreshold (small) oscillation of the neuron. The role of adaptation variable in neuron system is then to filtered many existing electrical processes and permit to adapt the system by the multiple transitions states in the chosen electrical mode. A fairly good agreement is observed between analytical and numerical results.
Optimization Approaches for Defining Storage Strategies in Maritime Container Terminals
Authors: Ambrosino Daniela , Xie Haoqi
Published: September 2021

In maritime container terminals, yards have a primary role in permitting the efficient management of import and export flows. In this work, a mixed 0/1 linear programming model and a heuristic approach are proposed for defining storage rules in order to minimize the space used in the export yard. The minimization of land space is pursued by defining the rules to allocate containers into the bay-locations of the yard, in such a way to minimise the number of bay-locations used and the empty slots within them. The main aim of this work is to propose a solution approach for permitting to the yard manager to compare yard storage strategies for different transport demands, in such a way to be able to evaluate and, eventually, change the storage strategy when the characteristics of the transport demand change. Computational experiments, based on both real instances and generated ones, are presented. All instances are derived by a case study related to an Italian terminal.
Spatial-temporal Patterns and Risk Factors for Human Leptospirosis in Thailand, 2012-2018
Authors: Chadsuthi Sudarat , Chalvet-Monfray Karine , Geawduanglek Suchada , Wongnak Phrutsamon , Cappelle Julien
Published: September 2021

Leptospirosis is a globally important zoonotic disease. The disease is particularly important in tropical and subtropical countries. Infections in humans can be caused by exposure to infected animals or contaminated soil or water, which are suitable for Leptospira. To explore the cluster area, the Global Moran’s I index was calculated for incidences per 100,000 population at the province level during 2012–2018, using the monthly and annual data. The high-risk and low-risk provinces were identified using the local indicators of spatial association (LISA). The risk factors for leptospirosis were evaluated using a generalized linear mixed model (GLMM) with zero-inflation. We also added spatial and temporal correlation terms to take into account the spatial and temporal structures. The Global Moran’s I index showed significant positive values. It did not demonstrate a random distribution throughout the period of study. The high-risk provinces were almost all in the lower north-east and south parts of Thailand. For yearly reported cases, the significant risk factors from the final best-fitted model were population density, elevation, and primary rice arable areas. Interestingly, our study showed that leptospirosis cases were associated with large areas of rice production but were less prevalent in areas of high rice productivity. For monthly reported cases, the model using temperature range was found to be a better fit than using percentage of flooded area. The significant risk factors from the model using temperature range were temporal correlation, average soil moisture, normalized difference vegetation index, and temperature range. Temperature range, which has strongly negative correlation to percentage of flooded area was a significant risk factor for monthly data. Flood exposure controls should be used to reduce the risk of leptospirosis infection. These results could be used to develop a leptospirosis warning system to support public health organizations in Thailand.
Persistence of E. Coli O157:H7 in Urban Recreational Waters From Spring and Autumn: A Comparison Analysis
Authors: Xie Yuang , Zhu Liyue , Lyu Guangze , Lu Lu , Ma Jinhua , Ma Jincai
Published: September 2021

Persistence of E. coli O157: H7 (EcO157) in 48 water samples (24 Spring samples and 24 Autumn samples) from 3 urban recreational waters in Changchun City was investigated, and multivariate statistical analysis was performed to correlate survival data with water physicochemical properties and bacterial communities. Our data showed that EcO157 survived longer in Spring samples than in Autumn samples regardless of the lakes. Results revealed that recreational water physicochemical properties and bacterial community in Spring samples were different from those in Autumn samples. Mantel and Partial Mantel tests, as well as co-occurrence network analysis illustrated that EC salinity, TOC and bacterial community were correlated with survival time (ttd) (p < 0.05). Variation partition analysis (VPA) indicated that bacterial community, EC, TOC and TN explained about 64.81% of overall ttd variation in Spring samples, and bacterial community, EC, pH and TP accounted for about 56.59% of overall ttd variation in Autumn samples. Structural equation model (SEM) illustrated that EC indirectly positively affected ttd through bacterial community. The correlation between bacterial community and ttd was negative in Spring samples and positive in Autumn samples. TN appeared a direct positive effect on ttd in Spring samples. TP displayed a direct negative effect on ttd in Autumn samples. Our results concluded that there was seasonal variation in environmental factors that directly or indirectly affected the survival of EcO157 in urban recreational waters.
Dietary Salt With Nitric Oxide Deficiency Induces Nocturnal Polyuria via Hyperactivation of Intrarenal Angiotensin Ⅱ-SPAK-NCC Pathway
Authors: Sekii Yosuke , Kiuchi Hiroshi , Takezawa Kentaro , Imanaka Takahiro , Kuribayashi Sohei , Okada Koichi , Inagaki Yusuke , Ueda Norichika , Fukuhara Shinichiro , Negoro Hiromitsu , Imamura Ryoichi , Nonomura Norio
Published: September 2021

Nocturnal polyuria is the most frequent cause of nocturia, a common disease associated with a compromised quality of life and increased mortality. Its pathogenesis is complex, and the detailed underlying mechanism remains unknown. Herein, we report that concomitant intake of a high-salt diet and reduced nitric oxide (NO) production achieved through Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) administration in mice resulted in nocturnal polyuria recapitulating the clinical features in humans. High salt intake under reduced NO production overactivated the angiotensin II-SPAK (STE20/SPS1-related proline–alanine-rich protein kinase)-NCC (sodium chloride co-transporter) pathway in the kidney, resulting in the insufficient excretion of sodium during the day and its excessive excretion at night. Excessive Na excretion at night in turn leads to nocturnal polyuria due to osmotic diuresis. Our study identified a central role for the intrarenal angiotensin II-SPAK-NCC pathway in the pathophysiology of nocturnal polyuria, highlighting its potential as a promising therapeutic target.
Two Different Approaches for Consistency of Intuitionistic Multiplicative Preference Relation using Directed Graph
Authors: Sahu Mamata , Gupta Anjana
Published: September 2021

Consistency is an important issue that causes wide public concern of decision-makers in the decision-making process. The lack of consistency in preference relations results in a vague solution. The main goal of this paper is to achieve the consistent intuitionistic multiplicative preference relation using a graphical approach. We have proposed two different characterizations of the consistency for intuitionistic multiplicative preference relation(IMPR). In the first approaches, we propose an algorithm to achieve the consistency of IMPR by using the cycles of various length in a directed graph.

The second approach proves isomorphism between the set of IMPRs and the set of asymmetric multiplicative preference relations. That result is explored to use the methodologies developed for asymmetric multiplicative preference relations to the case of IMPRs and achieve the consistency of asymmetric multiplicative preference relation using a directed graph. Sometimes the decision maker may not be able to provide the complete relation. So the above-said method is applied for an incomplete IMPR also, here consistency plays an important role. The examples are provided to illustrate both the methods in all cases.
Atom-Precise Fluorescent Copper Cluster for Tumor Microenvironment Targeting and Transient Chemodynamic Cancer Therapy
Authors: Yang Zhenzhen , Yang Anli , Ma Wang , Ma Kai , Lv Ya-Kun , Peng Peng , Li Bingjie , Zang Shuang-Quan
Published: September 2021

Background: Reactive oxygen species (ROS) have been widely studied for cancer therapy. Nevertheless, instability and aspecific damages to cellular biomolecules limited the application effect. Recently, significant research efforts have been witnessed in the flourishing area of metal nanoclusters (NCs) with atomically precise structures for targeted release of ROS but few achieved success towards targeting tumor microenvironment.Results: In this work, we reported an atomically precise nanocluster Cu6(C4H3N2S)6 (Cu6NC), which could slowly break and generate ROS once encountered with acidic. The as-prepared Cu6NC demonstrated high biological safety and efficient chemodynamic anti-tumor properties. Moreover, Cu6NC enabled transient release of ROS and contained targeting behavior led by the tumor microenvironment. Both in vitro and in vivo experiments confirmed that Cu6NC demonstrated a low cytotoxicity for normal cells, while presented high cytotoxicity for tumor cells with a concentration-dependent manner.Conclusions: This work not only reported a promising candidate for chemodynamic cancer therapy, but also paved the route to address clinical issues at the atomic level.
The Influence of the Windlass Mechanism on Kinematic and Kinetic Foot Joint Coupling
Authors: Williams Lauren , Ridge Sarah , Johnson A. Wayne , Arch Elisa S. , Bruening Dustin A.
Published: September 2021

Background: Previous research shows kinematic and kinetic coupling between the metatarsophalangeal (MTP) and midtarsal joints during gait. Studying the effects of MTP position as well as foot structure on this coupling may help determine to what extent foot coupling during dynamic and active movement is due to the windlass mechanism. This study’s purpose was to investigate the kinematic and kinetic foot coupling during controlled passive, active, and dynamic movements. Methods: After arch height and flexibility were measured, participants performed four conditions: Seated Passive MTP Extension, Seated Active MTP Extension, Standing Passive MTP Extension, and Standing Active MTP Extension. Next, participants performed three heel raise conditions that manipulated the starting position of the MTP joint: Neutral, Toe Extension, and Toe Flexion. A multisegment foot model was created in Visual 3D and used to calculate ankle, midtarsal, and MTP joint kinematics and kinetics. Results: Kinematic coupling (ratio of midtarsal to MTP angular displacement) was approximately six times greater in Neutral heel raises compared to Seated Passive MTP Extension, suggesting that the windlass only plays a small kinematic role in dynamic tasks. As the starting position of the MTP joint became increasingly extended during heel raises, the amount of negative work at the MTP joint and positive work at the midtarsal joint increased proportionally, while distal-to-hindfoot work remained unchanged. Correlations suggest that there is not a strong relationship between static arch height/flexibility and kinematic foot coupling. Conclusions: Our results show that there is kinematic and kinetic coupling within the distal foot, but this coupling is attributed only in small measure to the windlass mechanism. Additional sources of coupling include foot muscles and elastic energy storage and return within ligaments and tendons. Furthermore, our results suggest that the plantar aponeurosis does not function as a rigid cable but likely has extensibility that affects the effectiveness of the windlass mechanism. Arch structure did not affect foot coupling, suggesting that static arch height or arch flexibility alone may not be adequate predictors of dynamic foot function.
Drug-Induced Hepatic Injury in Newborns and Children in Intensive Care Unit: A Retrospective Study of China
Authors: Ye Ling , Guo Chengxian , Feng Zeying , Huang Longjian , Guo Chengjun , Wu Xiong , He Li , Tan Wei , Wang Yi , Wu Xuehong , Hu Biwen , Li Tong , Yang Guoping , He Qingnan
Published: September 2021

Purpose

Drug-induced liver injury (DILI) is a common adverse reaction in the clinic; however, there are relatively few reports of DILI in critically ill newborns and children. Making use of the Pediatric Intensive Care database (PIC), this study identifies which drugs are related to DILI in neonates and children in China.
Methods

Using the PIC, we screened for patients whose liver was suspected of being injured by drugs during hospitalization. The medicine they used was then assessed by the Roussel Uclaf Causality Assessment Method (RUCAM). We also collated drug combinations that may affect CYP enzyme metabolism, which may be one of the mechanisms that lead to DILI.
Results

A total of 13,449 patients were assessed, of whom 77 newborns and 261 children were finally included. The main type of liver injury in neonates was mixed (83.1%), while children’s hepatic injury types were mostly distributed between hepatocellular (59.4%) and cholestatic (28.4%). In terms of the assessment by the RUCAM, in newborns, the drugs that were most considered to cause or associated with hepatic injury comprised medium and long chain fat emulsion (17%), sodium glycerophosphate (12%) and meropenem (9%); while omeprazole (11%), methylprednisolone sodium succinate (10%) and meropenem (8%) are the primary culprit of DILI in children. Drug combinations that may affect CYP enzyme metabolism frequently seen in neonates are omeprazole + budesonide (16.9%), dexamethasone + midazolam (10.4%) and midazolam + sildenafil (10.4%). In children, the commonly used drug combinations are fentanyl + midazolam (20.7%), ibuprofen + furosemide (18.4%) and diazepam + omeprazole (15.3%).
Conclusions

The drugs that have been found to have hepatotoxicity (meropenem, medium and long chain fat emulsion, ibuprofen.etc.) are also related to DILI in newborns and children. When giving these drugs to newborns and children, physicians need to be more cautious. Also, pay attention to the effect on CYP 450 enzymes when using multiple drugs at the same time.
Possible role of melatonin in precocious and accelerated puberty in females during the COVID-19 pandemic
Authors: Stagi Stefano , Ferrari Marta , Paiusco Giada , Moriondo Maria , Azzari Chiara
Published: September 2021

BackgroundPubertal development is a complex process influenced by a multitude of factors; among these, the role of melatonin has only been partially investigated. During the COVID-19 pandemic an unexpected increase in cases of precocious and fast puberty was observed.AimsTo evaluate the possible role of salivary melatonin in precocious and accelerated puberty during the COVID-19 lockdown.Patients and MethodsFifty-four females were evaluated from October 2020 to March 2021; of these, 39 children were diagnosed with central precocious puberty (CPP) and 15 with isolated premature thelarche (IPT). Thirty-three healthy children acted as controls. The enrolled patients were asked to take measures the day before the visit to avoid influencing readings of melatonin secretion. Salivary melatonin levels were analyzed using commercially available ELISA kit.ResultsThere was no difference in the time from B2 to diagnosis (months) between IPT and CPP patients. However, the anamnestic and clinical data of our CPP patients confirmed an acceleration in the stages of pubertal development. As expected, subjects with CPP showed a significantly greater stature SDS and height velocity SDS. There were no differences in BMI SDS and Delta BMI SDS. Interestingly, we discovered a significant difference regarding the use of electronic devices between children with CPP, IPT and controls (p < 0.05). Children with CPP showed significantly lower values of salivary melatonin than patients with TPT and controls (p < 0.0001).DiscussionOur results showed a marked reduction in salivary melatonin in children with CPP diagnosed during and after lockdown for COVID-19. Larger studies are needed to confirm and investigate these findings.
CYP2J2 and EETs Protect Against Pulmonary Hypertension with Lung Ischemia-Reperfusion Injury In Vivo and In Vitro
Authors: Ding Yun , Tu Pengjie , Chen Yiyong , Huang Yangyun , Pan Xiaojie , Chen Wenshu
Published: September 2021

Background Cytochrome P450 epoxygenase 2J2 (CYP2J2) metabolizes arachidonic acid to epoxyeicosatrienoic acids (EETs), which exert anti-inflammatory, anti-apoptotic, pro-proliferative, and antioxidant effects on the cardiovascular system. However, the role of CYP2J2 and EETs in pulmonary arterial hypertension (PAH) with lung ischemia-reperfusion injury (LIRI) remains unclear. In the present study, we investigated the effects of CYP2J2 overexpression and exogenous EETs on PAH with LIRI in vitro and in vivo.Methods CYP2J2 gene was transfected into rat lung tissue by recombinant adeno-associated virus (rAAV) to increase the levels of EETs in serum and lung tissue. A rat model of PAH with LIRI was constructed by tail vein injection of monocrotaline (50 mg/kg) for 4 weeks, followed by clamping of the left pulmonary hilum for 1 h and reperfusion for 2 h. In addition, we established a cellular model of human pulmonary artery endothelial cells (HPAECs) with TNF-α combined with hypoxic reoxygenation (anoxia for 8 h and reoxygenation for 16 h) to determine the effect and mechanism of exogenous EETs.Results CYP2J2 overexpression significantly reduced the inflammatory response, oxidative stress and apoptosis associated with lung injury in PAH with LIRI. In addition, exogenous EETs suppressed inflammatory response and reduced intracellular reactive oxygen species (ROS) production and inhibited apoptosis in a tumor necrosis factor alpha (TNF-α) combined hypoxia-reoxygenation model of HPAECs. Our further studies revealed that the anti-inflammatory effects of CYP2J2 overexpression and EETs might be mediated by PPARγ pathway; the anti-apoptotic effects might be mediated by the PI3K/Ak pathway.Conclusions CYP2J2 overexpression and EETs protect against PAH with LIRI via anti-inflammation, anti-oxidative stress and anti-apoptosis, suggesting that increased levels of EETs may be a promising strategy for the prevention and treatment of PAH with LIRI.
Flood Hazard Assessment Under Climate Change Scenarios in Kelantan River Basin, Malaysia
Authors: Tam Tze Huey , Rahman Muhammad Zulkarnain Abdul , Harun Sobri , Try Sophal , Shahid Shamsuddin , Jamal Mohamad Hidayat , Ismail Zamri , Razak Khamarrul Azahari , Ghani Mohd Khairolden , Wahab Yusrin Faiz Abdul
Published: September 2021

Climate change can significantly alter the hydrological cycle and lead to severe hydrological disasters. This study aims to determine the impact of climate change on flood hazards in the Kelantan River Basin of Malaysia. The Climate Change Factor (CCF) is used to calculate 24-hour design rainfall with 50, 100 and 200-year return periods. A distributed hydrological model, Rainfall-Runoff-Inundation (RRI), is used to simulate flood inundation under current and future climate scenarios. The results indicate an increase in 50, 100, and 200 years, design rainfall, streamflow and flood hazard. The expected design rainfall and streamflow for 50, 100, and 200 years would increase by 36.6%, 37.9%, 42.7%, and 43.2%, 32.7%, 36.5%, respectively. Flood hazard is spatially variable in the Kelantan River Basin. Tanah Merah is the town that would face a significant increase in future flooding. The findings of this study can aid relevant agencies and government departments to comprehend the current and future flood hazard situation in the Kelantan River Basin. It would also assist them in formulating appropriate flood management strategies to mitigate future severe flood hazards.
6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio) hexanol ameliorates the progression of endometriosis by regulating GSTM4 expression to inhibit proliferation and induce apoptosis
Authors: Liu Wei , Zhang Na , Du Yanbo , Liu Xiaoqiang , Ma Jinlong , Yan Lei
Published: September 2021

Background: Endometriosis is a chronic disease associated with disorder of the oxidative balance and chronic inflammation. Although endometriosis is a benign disease, it has the characteristics properties similar to malignant cancer.Methods: The present study aim to investigate the role of glutathione S-transferase Mu class 4 (GSTM4), and tested if 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio) hexanol (NBDHEX) could regulate GSTM4 expression to affect cell proliferation, migration, invasion and apoptosis in endometriosis. Expression of GSTM4 was detected by immunohistochemistry in 15 cases of endometriosis patients and compared with 15 healthy controls. Primary endometrial cells were analyzed by western blotting (WB) to determine expression of GSTM4, PCNA, MMP-9, Survivin, Bcl-xl, Bax, Keap1 and Nrf2. CCK8 and transwell assays were used to study the effects of GSTM4 and NBEHEX on endometrial cells. The effect on apoptosis was analysised by flow cytometry. Results: The expression of GSTM4 was significantly increased in endometriosis than those from controls (p<0.01). The results suggested that NBDHEX negatively regulates GSTM4 expression, induces cell proliferation, migration, invasion, and promotes cell apoptosis. NBDHEX decreased the expression of GSTM4 (p<0.05), PCNA (p<0.05), MMP-9 (p<0.01), Survivin (p<0.05) and Bcl-xl (p<0.05) , along with increased expression of Bax (p<0.05). The results also showed that NBDHEX decreased the expression of Nrf2 (p<0.05), but had no effect on the expression of Keap1(p>0.05). After transfection with si-GSTM4, the protein level was down-regulated by nearly 70% (p<0.05). Silencing of GSTM4 depressed the proliferation, migration, invasion and gene expression of endometrial stromal cells in patients with endometriosis and controls. Knockdown of GSTM4 interacting with Nrf2 induced apoptosis by decreasing the expression of Survivin (p<0.05), Bcl-xl (p<0.05) and increasing the expression of Bax (p<0.05) , but it did not affect the expression of Keap1(p>0.05) in endometriosis and controls. Conclusions: Inhibition of GSTM4 by NBDHEX suppresses the cell viability growth, migration, invasion and interact with Nrf2 to induce apoptosis, but has no effect on the expression of Keap1 in endometriosis. The use of siRNA to knockdown GSTM4 more accurately confirmed its ability to ameliorate the progression of endometriosis. NBDHEX may have therapeutic potential in the treatment of endometriosis.
Quantitative Assessment the Longitudinal Changes of Pulmonary Vascular Counts in Chronic Obstructive Pulmonary Disease
Authors: Park Sang Won , Lim Myoung-Nam , Kim Woo Jin , Bak So Hyeon
Published: September 2021

BackgroundChest computed tomography(CT) is a widely used method to assess morphological and dynamic abnormalities in chronic obstructive pulmonary disease (COPD). The small pulmonary vascular cross-section (CSA), quantitatively extracted from volumetric CT, is a reliable indicator for predicting pulmonary vascular changes. CSA is associated with the severity of symptoms, pulmonary function tests (PFT) and emphysema and in COPD patients the severity increases over time. However, there are few studies of changes in vascular during longitudinal follow-up in COPD patients. We analyzed the correlation longitudinal changes in pulmonary vascular parameters with clinical parameters in COPD patients.Materials and MethodsA total of 288 subjects with COPD were investigated during follow up period up to 6 years. CT images were classified into five subtypes from normal to severe emphysema according to percentage of low-attenuation areas less than -950 and -856 Hounsfield units (HU) on inspiratory and expiratory CT (LAA-950, LAA-856exp). Total number of vessels (Ntotal) and total number of vessels with area less than 5 mm2 (N<5mm) per 1 cm2 of lung surface area (LSA) were measured at 6 mm from the pleural surface.ResultsNtotal/LSA and N<5mm/LSA changed from 1.16±0.27 to 0.87±0.2 and from 1.02±0.22 to 0.78±0.22, respectively, during Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage progression. Both parameters changed from normal to severe emphysema according to CT subtype from 1.39±0.21 to 0.74±0.17 and from 1.18±0.19 to 0.67±0.15, respectively. LAA-950 and LAA-856exp were negatively correlated with Ntotal/LSA (r=-0.738, -0.529) and N<5mm /LSA (r=-0.729, -0.497). On the other hand, pulmonary function test (PFT) results showed a weak correlation with Ntotal/LSA and N<5mm/LSA (r=0.205, 0.210). The depth in CT subtypes for longitudinal change both Ntotal/LSA and N<5mm/LSA was (-0.032, -0.023) and (-0.027) in normal and SAD, respectively.ConclusionsQuantitative computed tomography features faithfully reflected pulmonary vessel alterations, showing in particular that pulmonary vascular alteration started.Trial registrationWe obtained the written informed consent from all participants in this study and the approval for all processes by our institution Institutional Review Board.
Nanofiber Electrospinning Combined with Rotary Bioprinting for Fabricating Small-Diameter Vessels with Endothelium and Smooth Muscle
Authors: Jin Qianheng , Fu Yi , Zhang Guangliang , Xu Lei , Jin Guangzhe , Tang Linfeng , Ju Jihui , Zhao Weixin , Hou Ruixing
Published: September 2021

Background: Cardiovascular disease is responsible for a large number of deaths each year. Autologous vascular transplantation is still the best surgical intervention option, but the success rate is affected by many factors. Tissue engineering is a growing research area of great interest because it can produce bionic grafts to replace autologous tissue. Although many molding strategies have been tried, precellularization of small-diameter vascular grafts remains a research challenge. Here, a novel approach for fabricating bionic small-diameter vascular vessels with endothelial and smooth muscle cells is developed through combining nanofiber electrospinning and a specially-designed rotary bioprinter.Results: Combining and utilizing the advantages of nanofiber electrospinning and rotary printing, a tissue-engineered vascular tissue more suitable for biological transplantation is fabricated. Electrospun poly(ε-caprolactone) (PCL) provides good elasticity, and the electrospinning modification is beneficial for adhesion and functionalization of endothelial cells. A flat monolayer on the surface of PCL is formed after 7 days cultivation. Modification of the traditional three-dimensional (3D) bioprinter to increase rotation of the central axis used dual motors rotating clockwise and anticlockwise at the same speed increase stability during the printing process. This allowed a uniform dense methacrylated gelatin (GelMA) structure containing smooth muscle cells to be bioprinted with the cells are arranged linearly along the horizontal axis of rotation. Perfused with umbilical vein endothelial cells, a monolayer endothelial structure is formed. The two type cells maintain viability and proliferation in the structure during the process of cultivation. In addition, the bionic structureis superior to the natural blood vessel in anti-burst pressure and suture retention strength.Conclusion: By combining nanofiber electrospinning and modified rotary bioprinter, we successfully formed a small-diameter bionic vascular vessel with smooth muscle cells and endothelial cells. This method takes advantages of two advanced technologies and provides a new strategy for the development of bionic blood vascular tissue.
Staphylococcus Aureus Iron-Regulated Surface Determinant B (IsdB) Protein Interacts with von Willebrand Factor and Promotes Adherence to Endothelial Cells.
Authors: Alfeo Mariangela J , Pagotto Anna , Barbieri Giulia , Foster Timothy J , Vanhoorelbeke Karen , De Filippis Vincenzo , Speziale Pietro , Pietrocola Giampiero
Published: September 2021

Staphylococcus aureus is the cause of a spectrum of diseases in humans and animals. The molecular basis of this pathogenicity lies in the expression of a variety of virulence factors, including proteins that mediate adherence to the host plasma and extracellular matrix proteins. In this study, we discovered that the iron-regulated surface determinant B (IsdB) protein, besides being involved in iron transport and vitronectin binding, interacts with von Willebrand Factor (vWF). IsdB-expressing bacteria bound to both soluble and immobilized vWF. The binding of recombinant IsdB to vWF was blocked by heparin and reduced at high ionic strength. Furthermore, treatment with ristocetin, an allosteric agent that promotes the exposure of the A1 domain of vWF, potentiates the binding of IsdB to vWF. Both near-iron transporter motifs NEAT1 and NEAT2 of IsdB individually bound recombinant A1 domain with KD values in the micromolar range. The binding of IsdB and adhesion of S. aureus expressing IsdB to monolayers of activated endothelial cells was significantly inhibited by a monoclonal antibody against the A1 domain and by IsdB reactive IgG from patients with staphylococcal endocarditis. This suggests the importance of IsdB in adherence of S. aureus to the endothelium colonization and as potential therapeutic target.
Clinicopathological Characteristics, Survival Outcomes, and Genetic Alterations of Younger Patient With Gastric Cancer: Results From China National Cancer Center and cBioPortal
Authors: Niu Penghui , Huang Huang , Zhao Lulu , Wang Tongbo , Zhang Xiaojie , Wang Wanqing , Zhang Yawei , Guo Chunguang , Zhao Dongbing , Chen Ying-Tai
Published: September 2021

BackgroundSurvival outcomes of younger patients with gastric cancer (GC) remains controversial. The present study sought to explore clinicopathological characteristics, survival outcomes, and genetic alterations in the younger and older patients with GC.MethodsPatients with GC were identified from the China National Cancer Center Gastric Cancer Database (NCCGCDB) during 1998–2018. Survival analysis was conducted via Kaplan-Meier estimates and Cox proportional hazards models. Sequencing data were enrolled from the China National Cancer Center, TCGA, and MSKCC databases. ResultsA total of 1146 younger and 16988 older cases were included. Patients in the younger group were predominant in poor differentiation (53.7% versus 33.8%, P<0.0001), and pTNM stage IV (19.5% versus 11.8%, P<0.001). The 5-year overall survival (OS) of patients in NCCGCDB has noticeable increased from 1998 to 2018. Younger age was an independent prognostic factor for GC patients in pTNM stage III (P=0.014), while other stages showed no difference. Compared to the younger, older patients had a higher mutation frequency in LRP1B, GNAS, APC, KMT2D genes (all P< 0.05). In addition, although no significant difference, results of the China National Cancer Center, TCGA, and MSKCC cohorts indicated that younger patients dominated in CDH1, RHOA, and CTNNB1 mutations.ConclusionsStable proportion of younger cases and noticeable survival improvements were reported in the China National Cancer Center. Younger patients with pTNM stage III had a worse survival than older, while other tumor stages showed no difference. Furthermore, distinctive molecular characteristics were identified in younger GC patients, which might partly explain histopathological behaviors and prognosis of in this subpopulation.