bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trend of annual maximum rainfall in Campania region (Southern Italy)
Authors: Avino Angelo , Manfreda Salvatore , Cimorelli Luigi , Pianese Domenico 
Published: December 2021

AbstractExtreme rainfall events are increasing in both number and intensity at global scale; however, it is hard to quantify the impact of climate change at local scale given the strong temporal and spatial heterogeneity of this process. Moreover, limited data availability and its spatial variability requires significant effort to identify specific trends at the regional level. In this study, we attempt to construct a detailed description of rainfall patterns and trends over the Campania region, southern Italy. For this reason, the dataset of rainfall annual maxima in pre‐assigned durations was constructed using all available records and extended using interpolation methods such as inverse distance weighting and ordinary kriging methods. The rainfall dataset allowed actual trends over the region to be quantified using the Mann‐Kendall trend test and the record‐breaking analysis. The trend test reveals that most of the rainfall stations display no statistically significant trend, however, an increasing trend of extreme rainfall for short durations, in specific portions of the region, is observed.
Online promotion of resident research and research training among postgraduate year 1 (PGY1) pharmacy residency programs
Authors: Benyamin Olivia , Lambert Sydney , Mascarenas Kristi , Goodlet Kellie J. 
Published: December 2021

AbstractIntroductionNational pharmacy organizations advocate for training relating to the investigation and evaluation of scientific evidence. Accordingly, most postgraduate year 1 (PGY1) residents conduct longitudinal research. However, residents typically report low confidence in their research abilities and may benefit from structured training within the residency program. The purpose of this study was to assess how PGY1 programs promote research on their websites, including the proportion offering resident research training.MethodsPGY1 residency programs were identified using the American Society of Health‐System Pharmacists residency directory. Community‐based, managed care, or PGY1/postgraduate year 2 (PGY2) combined programs were excluded. Study data were extracted using the residency directory and program websites and included program characteristics, research requirements, dedicated research time, promotion of past research, research mentorship and support, and research training. Characteristics of the programs with and without research training were compared.ResultsOf 1139 PGY1 residency program websites, 3.0% had a highly prominent research section, 19.7% had a clear paragraph relevant to research information, 63.4% had minimal information on research, and 14.0% offered no research information. Forty‐one percent of PGY1 residency programs required dissemination of research findings via poster presentation, platform presentation, or completed manuscript. Fifty‐one programs (4.5%) provided research development training through seminars, a development program, or a certificate program. Compared with programs without research training, these programs were more likely to be fully accredited (100% vs 92.2%, P = .028), offer five or more PGY1 positions (25.5% vs 14.0%, P = .037), and offer one or more PGY2 specialty residencies (60.8% vs 35.6%, P < .001).ConclusionMost PGY1 program websites had minimal information related to resident research. Although the presentation and dissemination of research was a commonly listed residency requirement, less than 5% of programs indicated that they provide resident research development. Residency program directors should ensure that their program websites accurately reflect their residents' research experience, including development opportunities.
Vascularization in tissue engineering: The architecture cues of pores in scaffolds
Authors: Xia Ping , Luo Yongxiang 
Published: December 2021

AbstractVascularization is a key event and also still a challenge in tissue engineering. Many efforts have been devoted to the development of vascularization based on cells, growth factors, and porous scaffolds in the past decades. Among these efforts, the architecture features of pores in scaffolds played important roles for vascularization, which have attracted increasing attention. It has been known that the open macro pores in scaffolds could facilitate cell migration, nutrient, and oxygen diffusion, which then could promote new tissue formation and vascularization. The pore parameters are the important factors affecting cells response and vessel formation. Thus, this review will give an overview of the current advances in the effects of pore parameters on vascularization in tissue engineering, mainly including pore size, interconnectivity, pore size distribution, pore shape (channel structure), and the micro/nano‐surface topography of pores.
Ginsenoside‐Rg1 attenuates sepsis‐induced cardiac dysfunction by modulating mitochondrial damage via the P2X7 receptor‐mediated Akt/GSK‐3β signaling pathway
Authors: Liu Zhengyu , Pan Hongwei , Zhang Yixiong , Zheng Zhaofen , Xiao Weiwei , Hong Xiuqin , Chen Fang , Peng Xiang , Pei Yanfang , Rong Jingjing , He Jin , Zou Lianhong , Wang Jia , Zhong Jie , Han Xiaotong , Cao Yan 
Published: December 2021

AbstractGinsenoside‐Rg1 (G‐Rg1), a saponin that is a primary component of ginseng, is effective against inflammatory diseases. The P2X purinoceptor 7 (P2X7) receptor is an ATP‐gated ion channel that is predominantly expressed in immune cells and plays a key role in inflammatory processes. We investigated the role of G‐Rg1 in sepsis‐related cardiac dysfunction and the underlying mechanism involving the regulation of the P2X7 receptor. We detected cell viability, cytotoxicity, cellular reactive oxygen species (ROS) levels, and mitochondrial membrane potential (MMP) with or without G‐Rg1 in lipopolysaccharide (LPS)‐ or hypoxia/reoxygenation (H/R)‐induced H9c2 cell models of ischemia/reperfusion injury. We applied cecal ligation and puncture (CLP) to induce a mouse model of sepsis and measured the survival duration and cardiac function of CLP mice. Next, we quantified the ROS level, MMP, respiratory chain complex I–IV enzymatic activity, and mitochondrial fusion in CLP mouse heart tissues. We then investigated the role of G‐Rg1 in repairing LPS‐induced cell mitochondrial damage, including mitochondrial superoxidation products. The results showed that G‐Rg1 inhibited LPS‐ or H/R‐induced cardiomyocyte apoptosis, cytotoxicity, ROS levels, and mitochondrial damage. In addition, G‐Rg1 prolonged the survival time of CLP mice. G‐Rg1 attenuated LPS‐induced superoxide production in the mitochondria of cardiomyocytes and the excessive release of cytochrome c from mitochondria into the cytoplasm. Most importantly, G‐Rg1 suppressed LPS‐mediated induction of proapoptotic Bax, activated Akt, induced GSK‐3β phosphorylation, and balanced mitochondrial calcium levels. Overall, G‐Rg1 activates the Akt/GSK‐3β pathway through P2X7 receptors to inhibit sepsis‐induced cardiac dysfunction and mitochondrial dysfunction.
Smaller reaction volume of triplex taqman real‐time reverse transcription‐PCR assays for diagnosing coronavirus disease 2019
Authors: Dong Wenxue , Yang Xu , Li Jing , Zhang Zhiying , Liu Lijun , Zhao Zhipeng , Kang Longli 
Published: December 2021

AbstractBackgroundCoronavirus disease 2019 (COVID‐19) has had a devastating impact on public health services worldwide. Currently, there are no standard remedies or therapies for COVID‐19. it is important to identify and diagnose COVID‐19 to control the spread. But clinical symptoms of COVID‐19 are very similar to those of other respiratory viruses.ResultsAs a result, the diagnosis of COVID‐19 relies heavily on detecting pathogens. We established a bunch of triplex new TaqMan real‐time PCR assays. Three sets of primers and probes (targeting the ORF1ab, N, and E genes, respectively) are poorly consistent with other human coronaviruses and the human influenza virus. The sensitivity of established PCR assays notices as few as 100 copies per PCR of the ORF1ab, N, and E genes. Meanwhile, standard curves concluded from constant PCR reaction all showed glorious linear correlations between Ct values and the polymer loading copy variety (correlation coefficient (R2) of ORF1ab, N, and E genes is 0.996, 0.991, and 0.998, respectively). Surveillance of RNA‐based pseudovirus demonstrated that they were identified to be positive with respect to SARS‐CoV‐2 and that established PCR assays are achievable.ConclusionThe assays established provide a smaller reaction volume for diagnosing COVID‐19.
Evaluation of plasma circ_0006282 as a novel diagnostic biomarker in colorectal cancer
Authors: Mohammadi Davood , Zafari Yazdan , Estaki Zohreh , Mehrabi Mahdi , Moghbelinejad Sahar 
Published: December 2021

AbstractBackgroundNowadays, non‐invasive and rapid detection of cancers through molecular biomarkers has received much attention. Therefore, this study investigated the non‐invasive and rapid diagnosis of colorectal cancer through one of the newest biomarkers (circular RNA).MethodsFor this purpose, we collected tumoral, adjacent normal tissue, and plasma samples from 100 colorectal cancer (CRC) patients, 25 postoperative CRC patients, 28 colitis patients, and 108 healthy donors. First Illumina high‐throughput (Hi Seq 2000) sequencing was performed to identify known and novel differentially expressed circRNAs in the cancerous and adjacent normal tissues (n = 3). We used quantitative real‐time fluorescent polymerase chain reaction (qRT‐PCR) to detect the expression level of hsa_circ_0006282 among the different samples. Moreover, inter‐ and intra‐assays were performed to evaluate the potential of hsa_circ_0006282 as being a biomarker. The receiver operating characteristic curve (ROC) was drawn to appraise its diagnostic efficacy, and the sensitivity of this circ RNA was evaluated.ResultsBased on RNA‐sequencing results circ_0006282, cirs7, circ‐0001313, circ_0055625, circ_000984, circ_0055625, circ_0001178, circ_0071589, circ‐001569 were upregulated, and circ‐ITGA7, circ‐CDYL, circITCH, circ_0026344, circ_0000038, circ_0002220, circ_0067480, circIGHV3‐20‐1, circ_104916, circ_0009361 were downregulated circRNA. The hsa_circ_0006282 was the highest upregulated differentially expressed circRNA. Expression evaluation of this circRNA on different samples showed upregulation in CRC tissues (p < 0.0001) and plasma samples of CRC patients in comparison to healthy controls (p < 0.0001), while the area under the curve (AUC) was 0.831 (95% CI: 0.779–0.883). Expression of hsa_circ_0006282 in CRC patients decreased to normal after surgery (p < 0.0001). Our results showed high specificity and sensitivity of CRC detection when hsa_circ_0006282, carcinoembryonic antigen (CEA), and carbohydrate antigen199 (CA199) are combined.ConclusionPlasma hsa_circ_0006282 can be used as a novel diagnostic and dynamic monitoring biomarker in CRC patients.
The possible mechanism of Hippophae fructus oil applied in tympanic membrane repair identified based on network pharmacology and molecular docking
Authors: Huang Juntao , Teh Bing Mei , Xu Ziqian , Yuan Zhechen , Zhou Chongchang , Shi Yunbin , Shen Yi 
Published: December 2021

AbstractObjectiveThis study aimed to explore the mechanisms of Hippophae fructus oil (HFO) in the treatment of tympanic membrane (TM) perforation through network pharmacology‐based identification.MethodsThe compounds and related targets of HFO were extracted from the TCMSP database, and disease information was obtained from the OMIM, GeneCards, PharmGkb, TTD, and DrugBank databases. A Venn diagram was generated to show the common targets of HFO and TM, and GO and KEGG analyses were performed to explore the potential biological processes and signaling pathways. The PPI network and core gene subnetwork were constructed using the STRING database and Cytoscape software. A molecular docking analysis was also conducted to simulate the combination of compounds and gene proteins.ResultsA total of 33 compounds and their related targets were obtained from the TCMSP database. After screening the 393 TM‐related targets, 21 compounds and 22 gene proteins were selected to establish the network diagram. GO and KEGG enrichment analyses revealed that HFO may promote TM healing by influencing cellular oxidative stress and related signaling pathways. A critical subnetwork was obtained by analyzing the PPI network with nine core genes: CASP3, MMP2, IL1B, TP53, EGFR, CXCL8, ESR1, PTGS2, and IL6. In addition, a molecular docking analysis revealed that quercetin strongly binds the core proteins.ConclusionAccording to the analysis, HFO can be utilized to repair perforations by influencing cellular oxidative stress. Quercetin is one of the active compounds that potentially plays an important role in TM regeneration by influencing 17 gene proteins.
Clinical validation of the parent‐report Toronto Obsessive–Compulsive Scale (TOCS): A pediatric open‐source rating scale
Authors: Lambe Laura J. , Burton Christie L. , Anagnostou Evdokia , Kelley Elizabeth , Nicolson Robert , Georgiades Stelios , Soreni Noam , Schachar Russell J. , Hanna Gregory L. , Arnold Paul D. , Crosbie Jennifer 
Published: December 2021

AbstractBackgroundThere is a need to develop a multipurpose obsessive–compulsive disorder (OCD) measure that is useful for cross disorder research and as a reliable clinical rating scale. The current study examined the psychometric properties and established clinical cutoffs for the parent‐report version of the Toronto Obsessive–Compulsive Scale (TOCS), a 21‐item rating scale of obsessive–compulsive traits.MethodParticipants ranged in age from 6 to 21 years old and had a primary diagnosis of OCD (n = 350, 50% female), attention‐deficit/hyperactivity disorder (ADHD) (n = 820, 25% female), autism spectrum disorder (ASD) (n = 794, 22% female), or were typically developing controls (n = 391, 51% female). Confirmatory factor analyses, internal consistency reliability, and convergent and divergent validity of the TOCS were examined in the OCD group. Using various scoring approaches, receiver operating characteristic (ROC) analyses were used to establish a clinical cut‐off by splitting the OCD group into a discovery sample (166 OCD cases, 164 controls) and a validation sample (184 OCD cases, 227 controls). Classification accuracy and TOCS scores were compared across OCD, ADHD, and ASD groups.ResultsThe psychometric properties of the TOCS were confirmed. ROC analyses across TOCS scoring approaches in the discovery sample indicated excellent diagnostic discrimination (AUC ≥0.95, sensitivity 77%–92%, specificity 92%–98%). Established cutoffs, when applied in the independent validation sample of OCD cases and controls, showed an overall classification accuracy of 85%–90%. The TOCS total score and symptom count showed good discrimination of OCD from ADHD (AUC ≥0.86) and ASD (AUC ≥0.81). The OCD group scored significantly higher on all TOCS dimensions (except Hoarding) than the ADHD and ASD groups.ConclusionThe TOCS is a reliable and valid rating scale with strong sensitivity and specificity in discriminating OCD cases from controls, as well as from ASD and ADHD. It is a quantitative OCD measure with important clinical and research applications, with particular relevance for cross disorder phenotyping and population‐based studies.
Fabrication, characterization and evaluation of the effect of PLGA and PLGA–PEG biomaterials on the proliferation and neurogenesis potential of human neural SH‐SY5Y cells
Authors: Asghari Niari Shabnam , Rahbarghazi Reza , Salehi Roya , Kazemi Leila , Fathi Karkan Sonia , Karimipour Mohammad 
Published: December 2021

AbstractIn recent years with regard to the development of nanotechnology and neural stem cell discovery, the combinatorial therapeutic strategies of neural progenitor cells and appropriate biomaterials have raised the hope for brain regeneration following neurological disorders. This study aimed to explore the proliferation and neurogenic effect of PLGA and PLGA–PEG nanofibers on human SH‐SY5Y cells in in vitro condition. Nanofibers of PLGA and PLGA–PEG biomaterials were synthesized and fabricated using electrospinning method. Physicochemical features were examined using HNMR, FT‐IR, and water contact angle assays. Ultrastructural morphology, the orientation of nanofibers, cell distribution and attachment were visualized by SEM imaging. Cell survival and proliferation rate were measured. Differentiation capacity was monitored by immunofluorescence staining of Map‐2. HNMR, FT‐IR assays confirmed the integration of PEG to PLGA backbone. Water contact angel assay showed increasing surface hydrophilicity in PLGA–PEG biomaterial compared to the PLGA substrate. SEM analysis revealed the reduction of PLGA–PEG nanofibers' diameter compared to the PLGA group. Cell attachment was observed in both groups while PLGA–PEG had a superior effect in the promotion of survival rate compared to other groups (p < .05). Compared to the PLGA group, PLGA–PEG increased the number of Ki67+ cells (p < .01). PLGA–PEG biomaterial induced neural maturation by increasing protein Map‐2 compared to the PLGA scaffold in a three‐dimensional culture system. According to our data, structural modification of PLGA with PEG could enhance orientated differentiation and the dynamic growth of neural cells.
Mass spectrometry in the study of wood compounds released in the barrel‐aged wine and spirits
Authors: Flamini Riccardo , Panighel Annarita , De Marchi Fabiola 
Published: December 2021

AbstractAging of wines and spirits in wooden barrels is an industrial process used to stabilize the color, to improve the limpidity and to enrich the sensorial characteristics of the products. In red wines, the oxygen that permeates through the wood staves promotes the oxidization of polyphenols and the formation of new pigments with consequent stabilization of the wine color. Barrel aging of spirits, such as brandy, whisky, rum, and grappa is finalized to enrich their aroma and improve their sensorial characteristics by the contribute of the compounds released by the wood. Oak is the wood type mostly used in making barrels; however, an increasing interest in the use of chestnut, cherry, acacia, and in less extent, ash and mulberry, has been observed in the recent years. Gas chromatography‐mass spectrometry and liquid chromatography‐mass spectrometry are the main techniques used to characterize respectively the volatile and polar metabolites released by the wood barrels in the products. In this article are reported the recent advancements in this field.
Functional Topography of the Human Subthalamic Nucleus: Relevance for Subthalamotomy in Parkinson's Disease
Authors: Rodriguez‐Rojas Rafael , Pineda‐Pardo Jose A. , Mañez‐Miro Jorge , Sanchez‐Turel Alicia , Martinez‐Fernandez Raul , del Alamo Marta , DeLong Mahlon , Obeso Jose A. 
Published: December 2021

ABSTRACTBackgroundThe subthalamic nucleus (STN) is considered a key structure in motor, behavioral, and emotional control. Although identification of the functional topography of the STN has therapeutic implications in the treatment of the motor features of Parkinson's disease (PD), the details of its functional and somatotopic organization in humans are not well understood.ObjectiveThe aim of this study was to characterize the functional organization of the STN and its correlation with the motor outcomes induced by subthalamotomy.MethodsWe used diffusion‐weighted imaging to assess STN connectivity patterns in 23 healthy control subjects and 86 patients with PD, of whom 39 received unilateral subthalamotomy. Analytical tractography was used to reconstruct structural cortico‐subthalamic connectivity. A diffusion‐weighted imaging/functional magnetic resonance imaging–driven somatotopic parcellation of the STN was defined to delineate the representation of the upper and lower limb in the STN.ResultsWe confirmed a connectional gradient to sensorimotor, supplementary‐motor, associative, and limbic cortical regions, spanning from posterior‐dorsal‐lateral to anterior‐ventral‐medial portions of the STN, with intermediate overlapping zones. Functional magnetic resonance imaging–driven parcellation demonstrated dual segregation of motor cortico‐subthalamic projections in humans. Moreover, the relationship between lesion topography and functional anatomy of the STN explains specific improvement in bradykinesia, rigidity, and tremor induced by subthalamotomy.ConclusionsOur results support an interplay between segregation and integration of cortico‐subthalamic projections, suggesting the coexistence of parallel and convergent information processing. Identifying the functional topography of the STN will facilitate better definition of the optimal location for functional neurosurgical approaches, that is, electrode placement and lesion location, and improve specific cardinal features in PD. © 2021 International Parkinson and Movement Disorder Society
Safety and Efficacy of Mevidalen in Lewy Body Dementia: A Phase 2, Randomized, Placebo‐Controlled Trial
Authors: Biglan Kevin , Munsie Leanne , Svensson Kjell A. , Ardayfio Paul , Pugh Melissa , Sims John , Brys Miroslaw 
Published: December 2021

AbstractBackgroundMevidalen is a selective positive allosteric modulator (PAM) of the dopamine D1 receptor subtype.ObjectiveTo assess the safety and efficacy of mevidalen for treatment of cognition in patients with Lewy body dementia (LBD).MethodsPRESENCE was a phase 2, 12‐week study in participants with LBD (N = 344) randomly assigned (1:1:1:1) to daily doses of mevidalen (10, 30, or 75 mg) or placebo. The primary outcome measure was change from baseline on Cognitive Drug Research Continuity of Attention (CoA) composite score. Secondary outcomes included Alzheimer's Disease Assessment Scale‐Cognitive Subscale 13 (ADAS‐cog13), Movement Disorder Society‐Unified Parkinson's Disease Rating Scale (MDS‐UPDRS), and Alzheimer's Disease Cooperative Study‐Clinical Global Impression of Change (ADCS‐CGIC). Numerous safety measures were collected.ResultsMevidalen failed to meet primary or secondary cognition endpoints. Mevidalen resulted in significant, dose‐dependent improvements of MDS‐UPDRS total score (sum of Parts I−III, 10 mg P < 0.05, 30 mg P < 0.05, 75 mg P < 0.01, compared to placebo). The 30 mg and 75 mg mevidalen doses significantly improved ADCS‐CGIC scores compared to placebo (minimal or better improvement: 30 mg P < 0.01, 75 mg P < 0.01; moderate or better improvement: 30 mg P < 0.05, 75 mg P < 0.001). Increases in blood pressure, adverse events, and cardiovascular serious adverse events were most pronounced at the 75 mg dose.ConclusionsMevidalen harnesses a novel mechanism of action that improves motor symptoms associated with LBD on top of standard of care while improving or not worsening non‐motor symptoms associated with traditional dopaminergic therapy. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society