bluuebunny/crossref_metadata_2025_split huggingface dataset:
Japan's valsartan clinical trials shambles; time for fundamental changes
Authors: Ozaki Akihiko , Harada Kayo , Murayama Anju , Saito Hiroaki , Sawano Toyoaki , Tanimoto Tetsuya , Shrestha Sunil , Bhandari Divya , Crump Andy 
Published: February 2023

AbstractJapan's Diovan®/valsartan ‘scandal’ has received sensational coverage in the nation's media since 2012. Publication of fraudulent research and their subsequent retraction boosted and then curtailed the use of what was a useful therapeutic drug. Some authors of the papers resigned, others disputed the retractions and resorted to legal counsel to protect themselves. One individual, an undeclared Novartis employee involved in the research, was arrested. A complex and virtually unwinnable case was brought against him and Novartis, claiming that data alteration amounted to false advertising, but lengthy criminal court cases resulted in the case failing. Unfortunately, key elements, including conflicts of interest, pharmaceutical company interference in trials of its product, and the role of the institutions involved, have been effectively ignored. The incident also emphasised the fact that Japan's unique society and approach to science does not conform well to international standards. Although the supposed impropriety caused the appearance of a new Clinical Trials Act in 2018, the law has been criticized for being ineffectual and simply increasing clinical trial bureaucracy. This article examines the ‘scandal’ and identifies where changes must be made to clinical research and the roles of the various stakeholders in Japan to increase public trust in clinical trials and biomedical publications.
Groundwater recharge in northern New England: Meteorological drivers and relations with low streamflow
Authors: Crossett Caitlin C. , Hodgkins Glenn A. , Menk Hadley , Dupigny‐Giroux Lesley‐Ann L. , Dudley Robert , Lemcke‐Stampone Mary , Hammond John 
Published: February 2023

AbstractMeteorological drivers of groundwater recharge for spring (February–June), fall (October–January), and recharge‐year (October–June) recharge seasons were evaluated for northern New England and upstate New York from 1989 to 2018. Monthly groundwater recharge was computed at 21 observation wells by subtracting the water levels at the end of each month from the level of the previous month; only positive monthly values were used to compute seasonal recharge. Precipitation, temperature, sea‐level pressure, 500‐mb geopotential heights, and various teleconnection indices were tested as explanatory variables for the interannual variability of recharge using random forest machine learning models. Precipitation within recharge seasons was positively correlated with groundwater recharge for most wells in all seasons. In general, whilst groundwater recharge in the study area was generally highest during the months of March and April, October precipitation was an important month for explaining the interannual groundwater recharge variability. This is likely because the variability in recharge in October may be high or low for given years. Sea‐level pressure and 500‐mb heights were typically inversely correlated with groundwater recharge during the recharge‐year and fall recharge seasons, as higher sea‐level pressure and heights are usually associated with clearer skies and less precipitation. The North Atlantic Oscillation, Pacific‐North American pattern, and Pacific Decadal Oscillation teleconnections affected groundwater recharge differently by well and season. The influence of groundwater recharge on minimum daily streamflows during the subsequent summer/fall was also analysed. Summer precipitation was the most important explanatory variable for study streams whilst groundwater recharge and summer air temperature were significant variables for a few streams.
School counselors’ perceived school climate, leadership practice, psychological empowerment, and multicultural competence before and during COVID‐19
Authors: Hilts Derron , Liu Yanhong 
Published: February 2023

AbstractFollowing a population‐based randomized design, we investigated changes of school counselors’ psychological empowerment, multicultural competence, and leadership practice, as well as their perception of school climate from before to during COVID‐19. Specifically, school counselors were randomized into two conditions: (a) the pre‐COVID‐19 condition (n = 506) and (b) the current‐COVID‐19 condition (n = 542). Participants in the pre‐COVID condition responded to survey items following a retrospective manner based on their experiences between September 2019 and March 2020. We found that participants in the current COVID‐19 condition scored significantly higher in psychological empowerment and perceived school climate and lower in multicultural competence and leadership practices compared to the participants in the pre‐COVID‐19 condition. Regardless of directionality of changes, results supported the significant impacts that the pandemic had on school counselors’ roles related to addressing systemic issues. We discussed implications of the results to school counseling practice and school counselor training.
Chronic morphine exposure and maternal separation induce impairments in cognition and locomotor activity of male adolescent rats
Authors: Fadaei‐kenarsary Maysam , Esmaeilpour Khadijeh , Shabani Mohammad , Joushi Sara , Sheibani Vahid 
Published: February 2023

AbstractMaternal morphine exposure reduces motivation for basic cognitive tasks, followed by executive function deficits in attention and accuracy. It also induces depression‐like behaviors and has negative consequences for learning and memory in offspring. Interaction between mothers and pups has a crucial effect on the mammal's development. Maternal separation (MS) can originate behavioral and neuropsychiatric abnormalities later in life. It seems that adolescents are more susceptible to the effects of early‐life stress; Therefore, this study aimed to evaluate the effects of chronic morphine consumption (21 days before and after mating and gestation) and MS (180 min/day from postnatal day [PND] 1–21) on the cognitive and behavioral performance of male offspring in mid‐adolescence. Six groups, including control, MS, V (vehicle), morphine, V+MS, and morphine+MS, were tested for open field (OF), novel object recognition (NOR), and the Morris water maze (MWM). The results of the OF test showed that MS increased locomotor activity and movement velocity. Inner and outer zone durations did not differ among groups. The body stretching of the morphine+MS rats was significantly more than the MS rats. Moreover, the MS and morphine+MS groups showed significantly less sniffing behavior in the OF test. The MS group showed deficits in spatial learning in the MWM test, but recognition memory in the NOR and spatial memory in the MWM tests were not significantly different among groups. We concluded that MS could induce impairments in spatial learning and locomotor activity that could be worsened by maternal morphine exposure in adolescent male rats.
Morphological examination and scanning electron microscopy of the barn owl's (Tyto alba) tongue
Authors: Ozkadif Sema , Haligur Ayse , Haligur Mehmet , Alan Aydin 
Published: February 2023

AbstractThe beak structure changes according to the feeding patterns of birds. Further, the morphological and histological structures of their tongues vary. Therefore, the current study aimed to perform macroanatomical and histological examinations and scanning electron microscopy of the barn owl's (Tylo alba) tongue. Two dead barn owls were brought to the anatomy laboratory and were used as study material. The tongue of the barn owl was long, triangular‐shaped with a bifurcated tip. There were no papillae in the anterior 1/3 of the tongue, and the lingual papillae were shaped toward the back. The radix linguae were surrounded by a single row of conical papillae. Irregular thread‐like papillae were found on both sides of the tongue. The salivary gland ducts were on the lateral margin of the corpus linguae and the dorsal surface of the radix linguae. The lingual glands were in the lamina propria near the stratified squamous epithelium layer of the tongue. The dorsal surface of the tongue comprised non‐keratinized stratified squamous epithelium, and the ventral surface and caudal part of the tongue had keratinized stratified squamous epithelium. Hyaline cartilages were detected in the connective tissue immediately below the non‐keratinized stratified squamous epithelium on the dorsal surface of the root of the tongue. The study results can contribute to the current knowledge on the anatomical structure of birds. Further, they can be useful in managing the barn owl when used as companion animals and in research activity.
Receptor‐binding domain‐based SARS‐CoV‐2 vaccine adjuvanted with cyclic di‐adenosine monophosphate enhances humoral and cellular immunity in mice
Authors: Germanó María José , Giai Constanza , Cargnelutti Diego Esteban , Colombo María Isabel , Blanco Sebastián , Konigheim Brenda , Spinsanti Lorena , Aguilar Javier , Gallego Sandra , Valdez Hugo Alberto , Mackern‐Oberti Juan Pablo , Sanchez Maria Victoria 
Published: February 2023

AbstractNovel adjuvants are highly desired to improve immune responses of SARS‐CoV‐2 vaccines. This work reports the potential of the stimulator of interferon genes (STING) agonist adjuvant, the cyclic di‐adenosine monophosphate (c‐di‐AMP), in a SARS‐CoV‐2 vaccine based on the receptor binding domain (RBD). Here, mice immunized with two doses of monomeric RBD adjuvanted with c‐di‐AMP intramuscularly were found to exhibit stronger immune responses compared to mice vaccinated with RBD adjuvanted with aluminum hydroxide (Al(OH)3) or without adjuvant. After two immunizations, consistent enhancements in the magnitude of RBD‐specific immunoglobulin G (IgG) antibody response were observed by RBD + c‐di‐AMP (mean: 15360) compared to RBD + Al(OH)3 (mean: 3280) and RBD alone (n.d.). Analysis of IgG subtypes indicated a predominantly Th1‐biased immune response (IgG2c, mean: 14480; IgG2b, mean: 1040, IgG1, mean: 470) in mice vaccinated with RBD + c‐di‐AMP compared to a Th2‐biased response in those vaccinated with RBD + Al(OH)3 (IgG2c, mean: 60; IgG2b: n.d.; IgG1, mean: 16660). In addition, the RBD + c‐di‐AMP group showed better neutralizing antibody responses as determined by pseudovirus neutralization assay and by plaque reduction neutralization assay with SARS‐CoV‐2 wild type. Moreover, the RBD + c‐di‐AMP vaccine promoted interferon‐γ secretion of spleen cell cultures after RBD stimulation. Furthermore, evaluation of IgG‐antibody titers in aged mice showed that di‐AMP was able to improve RBD‐immunogenicity at old age after 3 doses (mean: 4000). These data suggest that c‐di‐AMP improves immune responses of a SARS‐CoV‐2 vaccine based on RBD, and would be considered a promising option for future COVID‐19 vaccines.
Biphasic alcoholysis coupled with high‐speed countercurrent chromatography for high performance on separating phorbol from Croton tiglium Linn extracts
Authors: Fan Jie‐Ping , He Ban‐Tian , Gao Yi , Xie Chun‐Fang , Chen Hui‐Ping , Peng Hai‐Long 
Published: February 2023

Phorbol is a tetracyclic diterpenoid found in Euphorbia tirucalli, Croton tiglium, and Rehmannia glutinosa, and is nuclear of various phorbol esters. The rapid obtaining of phorbol with high purity highly contributes to its application, such as synthesizing phorbol esters with designable side chains and particular therapeutic efficacy. This study introduced a biphasic alcoholysis method for obtaining phorbol from croton oil by using polarity imparity organic solvents in both phases and established a high‐speed countercurrent chromatography method for simultaneous separation and purification of phorbol. The optimized operation conditions of biphasic alcoholysis were a reaction time of 91 min, a temperature of 14°C, and a croton oil‐methanol ratio of 1:30 (g:ml). The phorbol during the biphasic alcoholysis was 3.2‐fold higher in content than that obtained in conventional monophasic alcoholysis. The optimized high‐speed countercurrent chromatography method was using the ethyl acetate/n‐butyl alcohol/water at 4.7:0.3:5 (v:v:v) with Na2SO4 at 0.36 g/10 ml as the solvent system, using the mobile phase flow rate of 2 ml/min, the revolution of 800 r/min, under which the retention of the stationary phase was achieved at 72.83%. The crystallized phorbol following high‐speed countercurrent chromatography was obtained as high purity of 94%.
Design of the new guide vane for the turbo air classifier
Authors: Yu Y. , Chen W. , Kong X. , Ren C. , Liu J. 
Published: February 2023

AbstractThe guide vane is a common guide part in a turbo air classifier. However, there is a lack of a theoretical design basis and an analogy method is often used to design the guide vanes. The guide vanes’ effects of improving the flow field distribution are obtained by means of comparison of the flow field of the classifiers with and without guide vanes. However, the guide vane of a 15° setting angle should be optimized due to the non‐uniform airflow circumferential distribution in the annular region. To obtain a well‐distributed flow field of a turbo air classifier, a design method for the guide vane is provided based on the airflow trajectory in the volute and a new guide vane of a 10° setting angle is designed under the operating condition of 12–1200. The numerical simulation results show that the standard deviation of circumferential radial and tangential velocity is decreased. Besides, the trajectories of the particles with the same size in different circumferential positions show their classification results are consistent. This guide vane design method is feasible and provides the design references for the turbo air classifiers.
Protective effect of saffron carotenoids against amyloid beta‐induced neurotoxicity in differentiated PC12 cells via the unfolded protein response and autophagy
Authors: Sanjari‐Pour Mariam , Faridi Nassim , Wang Ping , Bathaie S. Zahra 
Published: February 2023

AbstractThe preventive effect of saffron against Alzheimer's disease (AD) has been reported. Herein, we studied the effect of Cro and Crt, saffron carotenoids, on the cellular model of AD. The MTT assay, flow cytometry, and elevated p‐JNK, p‐Bcl‐2, and c‐PARP indicated the AβOs‐induced apoptosis in differentiated PC12 cells. Then, the protective effects of Cro/Crt on dPC12 cells against AβOs were investigated in preventive and therapeutic modalities. Starvation was used as a positive control. RT‐PCR and Western blot results revealed the reduced eIF2α phosphorylation and increased spliced‐XBP1, Beclin1, LC3II, and p62, which indicate the AβOs‐induced autophagic flux defect, autophagosome accumulation, and apoptosis. Cro and Crt inhibited the JNK‐Bcl‐2‐Beclin1 pathway. They altered Beclin1 and LC3II and decreased p62 expressions, leading cells to survival. Cro and Crt altered the autophagic flux by different mechanisms. So, Cro increased the rate of autophagosome degradation more than Crt, while Crt increased the rate of autophagosome formation more than Cro. The application of 4μ8C and chloroquine as the inhibitors of XBP1 and autophagy, respectively, confirmed these results. So, augmentation of the survival branches of UPR and autophagy is involved and may serve as an effective strategy to prevent the progression of AβOs toxicity.
Fast estimation of mixed‐effects location‐scale regression models
Authors: Gill Nathan , Hedeker Donald 
Published: February 2023

SummaryAs a result of advances in data collection technology and study design, modern longitudinal datasets can be much larger than they historically have been. Such “intensive" longitudinal datasets are rich enough to allow for detailed modeling of the variance of a response as well as the mean, and a flexible class of models called mixed‐effects location‐scale (MELS) regression models are commonly used to do so. However, fitting MELS models can pose computational challenges related to the numerical evaluation of multi‐dimensional integrals; the slow runtime of current methods is inconvenient for data analysis and makes bootstrap inference impractical. In this paper, we introduce a new fitting technique, called FastRegLS, that is considerably faster than existing techniques while still providing consistent estimators for the model parameters.
Through Space Sigma Donation π Acceptor Assisted Photocatalytic Degradation of Ciprofloxacin on TCPP Supported g‐C3N4
Authors: Joseph Merin , Sadik N. K Mohammed , Remello Sebastian Nybin , Haridas Suja , De Susmita 
Published: February 2023

AbstractPhotocatalysis on pristine g‐C3N4 (CN) often suffers from fast recombination of photogenerated electrons and holes. Herein, we demonstrate the superior photocatalytic performance of free base tetrakis(4‐carboxyphenyl) porphyrin (TCPP) – g‐C3N4 (CN/TCPP) hybrids synthesised by a facile ultrasound aided impregnation. Structural and morphological characterisation confirmed the successful formation of the hybrid via noncovalent π–π stacking. Optical/electrochemical characterisation, as well as DFT study, designates the shifting of the optical absorption edge to visible range along with inhibition of carrier recombination through enhanced charge transfer. The CN/TCPP hybrids exhibited superior performance towards the degradation of persistent antibiotic ciprofloxacin under visible irradiation signifying its enhanced visible light sensitivity. The enhanced photocatalytic activity of CN/TCPP is ascribed to the charge transfer by through‐space conjugation by migration of electrons and holes in opposite directions, which minimises the possibility of electron‐hole recombination. From the LCMS data, scavenging studies, and first principles DFT analysis, the photodegradation of CIP is proposed to proceed via the destruction of the piperazine ring initiated mainly through the electrophilic attack by the holes.
N‐Coordinated Cu–Ni Dual‐Single‐Atom Catalyst for Highly Selective Electrocatalytic Reduction of Nitrate to Ammonia
Authors: Wang Yunlong , Yin Haibo , Dong Feng , Zhao Xiaoguang , Qu Yakun , Wang Lixin , Peng Yue , Wang Dingsheng , Fang Wei , Li Junhua 
Published: February 2023

AbstractAs a traditional method of ammonia (NH3) synthesis, Haber–Bosch method expends a vast amount of energy. An alternative route for NH3synthesis is proposed from nitrate (NO3−) via electrocatalysis. However, the structure–activity relationship remains challenging and requires in‐depth research both experimentally and theoretically. Here an N‐coordinated Cu–Ni dual‐single‐atom catalyst anchored in N‐doped carbon (Cu/Ni–NC) is reported, which has competitive activity with a maximal NH3Faradaic efficiency of 97.28%. Detailed characterizations demonstrate that the high activity of Cu/Ni–NC mainly comes from the contribution of Cu–Ni dual active sites. That is, (1) the electron transfer (Ni → Cu) reveals the strong electron interaction of Cu–Ni dual‐single‐atom; (2) the strong hybridizations of Cu 3d—and Ni 3d—O 2p orbitals of NO3−can accelerate electron transfer from Cu–Ni dual‐site to NO3−; (3) Cu/Ni–NC can effectively decrease the rate‐limiting step barriers, suppress N–N coupling for N2O and N2formation and hydrogen production.
Stimuli‐responsive silk fibroin for on‐demand drug delivery
Authors: Lin Xiang , Cai Lijun , Cao Xinyue , Zhao Yuanjin 
Published: February 2023

AbstractStimuli‐responsive “smart” hydrogel biomaterials have attracted great attention in the biomedical field, especially in designing novel on‐demand drug delivery systems. As a handful natural biomaterial approved by US Food and Drug Administration, silk fibroin (SF) has unique high temperature resistance as well as tunable structural composition. These properties make it one of the most ideal candidates for on‐demand drug delivery. Meanwhile, recent advances in polymer modification and nanomaterials have fostered the development of various stimuli‐responsive delivery systems. Here, we first review the recent advance in designing responsive SF‐based delivery systems in different stimulus sources. These systems are able to release mediators in a desired manner in response to specific stimuli in active or passive manners. We then describe applications of these specially designed responsive delivery systems in wound healing, tumor therapy, as well as immunomodulation. We also discuss the future challenges and prospects of stimuli‐responsive SF‐based delivery systems.
Study on early accurate diagnosis and treatment of COVID‐19 with smart phone tracking using bionics
Authors: Gupta Shweta , Kumar Adesh 
Published: February 2023

AbstractThe replication of biological systems by mechanical and electronic devices is referred to as bionics. The bionics industry has grown along four primary application areas, in addition to hearing, vision, orthopedics, and a small, dispersed group of implants that enhance cardiac and neurological functions. The SARS‐CoV‐2 virus is the infectious disease known as coronavirus disease (COVID‐19). The virus‐infected people require assistance to better understand the situation caused by COVID‐19 and to bring some easy, efficient, and effective solutions. One of the solutions mentioned for the early stages involves wearable sensors with temperature sensors for early Covid‐19 identification and photos delivered to an AI‐enabled smartphone, robotic sensor, or robot itself. In severe situations, lung X‐ray images are captured by robotic and remote sensors, and the lungs are given the right medication to finish off the virus. The paper presents the study on the overview, applications of artificial intelligence, and deep learning from the bionics point of view. Deep learning and machine learning will be used for reducing the Covid‐19 outbreak. Wearable sensors provide important data by having temperature‐embedded sensors in several physical devices that reveal details about the environment and body that are connected. Covid‐19 probability prediction is aided by smartphones with artificial intelligence and machine learning capabilities. Case history, doctor notes, chest X‐ray reports, details on the sites of breakouts, and other criteria can help forecast the severity of Covid‐19 when it is in its severe phases and direct the administration of medication to a specific area of the lungs.
Nickel induces hepatotoxicity by mitochondrial biogenesis, mitochondrial dynamics, and mitophagy dysfunction
Authors: Guo Hongrui , Wei Ling , Wang Yihan , Cui Hengmin , Deng Huidan , Zhu Yanqiu , Deng Junliang , Geng Yi , Ouyang Ping , Lai Weiming , Du Zongjun , Ni Xueqin , Yin Heng , Fang Jing , Zuo Zhicai 
Published: February 2023

AbstractNickel (Ni) is an important and widely hazardous chemical industrial waste. Excessive Ni exposure could cause multi‐organs toxicity in human and animals. Liver is the major target organ of Ni accumulation and toxicity, however, the precise mechanism is still unclear. In this study, nickel chloride (NiCl2)‐treatment induced hepatic histopathological changes in the mice, and, transmission electron microscopy results showed mitochondrial swollen and deformed of hepatocyte. Next, the mitochondrial damages including mitochondrial biogenesis, mitochondrial dynamics, and mitophagy were measured after NiCl2 administration. The results showed that NiCl2 suppressed mitochondrial biogenesis by decreasing PGC‐1α, TFAM, and NRF1 protein and mRNA expression levels. Meanwhile, the proteins involved in mitochondrial fusion were reduced by NiCl2, such as Mfn1 and Mfn2, however, mitochondrial fission proteins Drip1 and Fis1 were significantly increased. The up‐regulation of mitochondrial p62 and LC3II expression indicated that NiCl2 increased mitophagy in the liver. Moreover, the receptor‐mediated mitophagy and ubiquitin (Ub)‐dependent mitophagy were detected. NiCl2 promoted PINK1 accumulation and Parkin recruitment on mitochondria. And, the receptor proteins of mitophagy Bnip3 and FUNDC1 were increased in the NiCl2‐treated mice liver. Overall, these results show that NiCl2 could induce mitochondria damage in the liver of mice, and, dysfunction of mitochondrial biogenesis, mitochondrial dynamics and mitophagy involved in the molecular mechanism of NiCl2‐induced hepatotoxicity.