bluuebunny/crossref_metadata_2025_split huggingface dataset:
COVID-19 impact on the decision process of the Italian Medicine Agency: a quantitative assessment
Authors: Canali Beatrice , Candelora Laura , Fiorentino Francesca , Halmos Tom , La Malfa Paola , Massara Francesca , Vassallo Chiara , Urbinati Duccio 
Published: May 2023

Background: Since the COVID-19 pandemic has placed more attention on drugs’ approval process and the importance of rapid decision-making in the healthcare sector, it is crucial to assess how time to market (TTM) of drugs varied.
Objective: To estimate the impact of the COVID-19 pandemic on TTM of drugs in Italy.
Methods: An IQVIA database was used to retrieve information on drugs that obtained positive opinion from the Committee for Medicinal Products for Human Use between January 2015 and December 2021. The available observations were divided into three groups (Pre COVID, Partially COVID, and Fully COVID) according to the timing of their negotiation process. Differences in average TTM among the three groups were analyzed in three steps: (1) descriptive statistics; (2) univariate analysis; (3) multivariate analysis, using a matching estimator.
Results: A total of 363 unique combinations of molecule and indication met the inclusion criteria: 174 in the Pre COVID group, 69 in the Partially COVID group, and 123 in the Fully COVID group. Descriptive statistics and univariate analysis found a statistically significant difference in TTM among the three periods, with average TTM increasing during the pandemic (+136 days, p = 0.00) and then decreasing afterward (−23 days, p = 0.09). In the matching analysis, results for the Partially COVID period were confirmed (+108 days, p = 0.00) while results for the Fully COVID period lost significance but maintained a negative sign.
Conclusions: The results suggest that after an adjustment phase in the Partially COVID period, a return to the status quo was reached.
Manchamento de dentes por extrato de própolis verde: ensaio in vitro
Authors: Teodoro Elaine Cristina Martinez , Costa Natália Alves , Carvalho Claudemir de , Palhari Fabiana Tavares Lunardi 
Published: May 2023

Na odontologia, a própolis tem despertado interesse devido aos seus resultados satisfatórios obtidos em diversas especialidades. O objetivo deste estudo foi verificar se o extrato de própolis verde aplicado em concentrações de 17% e 21% na dentina exposta de dentes bovinos hígidos foi capaz de promover um efeito de manchamento na respectiva estrutura dentária. Trata-se de um estudo experimental no qual foram utilizadas 40 coroas de dentes bovinos hígidos seccionados ao meio, em corte axial, no sentido mésio distal, a fim de expor a dentina. Os espécimes foram enumerados e divididos aleatoriamente em quatro Grupos (G1 a G4) para a realização do condicionamento ácido a fim de simular a dentina hipersensível e posteriormente receberam aplicação das soluções de extrato de própolis verde, utilizado como possível agente obliterador no tratamento da hipersensibilidade dentinária, sendo: Grupo 1 (G1): ácido fosfórico a 37% e extrato de própolis a 17% sem escovação, Grupo 2 (G2): ácido fosfórico a 37% e extrato de própolis a 21% sem escovação, Grupo 3 (G3): ácido fosfórico a 37% e extrato de própolis a 17% com escovação e Grupo 4 (G4): ácido fosfórico a 37% e extrato de própolis a 21% com escovação. Na semana seguinte à aplicação dos extratos de própolis, os dentes foram submetidos a um procedimento de profilaxia e observou-se que em todos eles a solução permaneceu fixada, conferindo um efeito de manchamento tanto na dentina como no esmalte. Pode-se concluir que o extrato de própolis verde proporcionou um efeito de manchamento nos dentes bovinos estudados.
ZIRCONIUM AND HAFNIUM DIHYDROXY­PHTHALO­CYANINATES: METHODS OF SYNTHESIS AND REACTIVITY
Authors: Chernii Viktor , Tretyakova Iryna , Fedosova Natalia , Denisenko Iryna , Dovbii Yan , Kovalska Vladyslava 
Published: May 2023

Usually in order to obtain out-of-plane sub­stituted phthalocyanine complexes of zirconium and hafnium (PcML2), the reaction of substitution of chlorine atoms in dichloridophthalocyaninates PcMCl2 is used. How­ever, this method has some limitations because during this reaction, hydrogen chloride is released, which can initiate the hydrolysis of starting compounds sensitive to an acidic environment, in particular, β-ketoesters, which, in turn, can lead to the formation of by-pro­ducts and, accordingly, to a decrease purity and yield of target complexes. At the same time, in similar reactions in which the initial phthalocyanine compounds are dihydroxyphthalocyaninates of zirconium and hafnium (PcM(OH)2), as a result of interaction with dicarbonyl compounds or carboxylic acids, water is formed, which does not have a negative effect on the starting substances or on the course of the reaction as a whole. Methods of obtaining zirconium and hafnium dihydroxyphthalocyaninates based on metal alkoxides and by hydrolysis of the corresponding PcMCl2 were investigated in the work. It was established that the synthesis of PcM(OH)2 based on the corresponding alkoxides occurs with low yields (25–40%), increasing the reaction temperature from 140 to 220oC does not lead to their significant increase. It was found that the hydrolysis of PcMCl2 should be carried out under more stringent conditions than previously described, which makes it possible to obtain PcM(OH)2 with high yields.
The reactivity of PcM(OH)2 was investigated when interacting with β-diketones and aliphatic carboxylic acids and compared with the reactivity of PcMCl2. It was established that the reactivity of PcM(OH)2 is similar to PcMCl2. However, it should be noted that in the case of the synthesis of β-ketoesterphthalocyanine complexes, the use of the corresponding PcM(OH)2 leads to a significant increase in the yield of the final products of the reaction compared to PcMCl2. This effect can be explained by the fact that hydrogen chloride is not released during the reaction with PcM(OH)2 and, accordingly, hydrolysis of the ester group does not occur.
21st-Century Skills and Lateral Thinking Dispositions of Nursing Students: An Example Global Pandemic
Authors: ÇOBAN Niran , GÖKTAŞ Sonay , GEZGİNCİ Elif , ŞENDİR Merdiye 
Published: May 2023

Objective: The aim of this study was to determine the 21st-century skills and lateral thinking dispositions of nursing students during the pandemic process. Speed of technological changes accesses the highest level in the current century. Following the technology and usability rate is going down among the world population. The ability of new technology usage created a new social class in society. This differentiation
positively or negatively affects the social and economic status of modern human thinking ability, creativity, and life quality. Especially after the COVID-19 pandemic, the ability of current technology usage made a big difference among people to access information and education.
Methods: This cross-sectional study is descriptive and relational. The research was conducted with 409 students studying at the Faculty of Nursing of a state university in Istanbul, Turkey.
Individual Characteristics Questionnaire, Multidimensional 21st Century Skills Scale, and Lateral Thinking Disposition Scale were used to obtain research data. The data obtained were analysed by number, descriptive statistics, Kolmogorov-Smirnov, Kruskal-Wallis and Mann-Whitney U tests.
Results: The results showed that nursing students were able to improve lateral thinking during pandemic. The male students have a significantly higher advantage of using technology compared with female students (p
The Turkish Validity and Reliability of The Adolescent Dysmenorrhea Self-Care Scale
Authors: SÜRÜCÜ Enise , ERGÜN Ayşe 
Published: May 2023

Objective: Dysmenorrhea is a common health problem that negatively affects daily life and academic skills when not managed well. This study was conducted to examine the Turkish validity and reliability of the Adolescent Dysmenorrhea Self-Care Scale.
Methods: This methodological study was conducted in 7 high schools in Bursa, Turkey. The research was carried out with 1041 high school students who met the participation criteria. The Adolescent Dysmenorrhea Self-Care Scale was adapted to Turkish by using translation-back translation method. The validity of the scale was evaluated with the content validity index, confirmatory factor analysis, similarity and discriminant validity coefficients and reliability, item-total correlation, internal consistency coefficient and test-retest analysis.
Results: According to the evaluations of the 10 experts whose opinions were taken for the Content Validity, it is determined that each item scored above 3 (3.52-4.00), and the mean score was 3.92 ± 0.14 and the content validity index was .98. Cronbach’s alpha reliability coefficient was found α = .96. Confirmatory factor analysis fit indexes and similarity and discriminant validity coefficients showed that the scale has sufficient compatibility with the theoretical six-factor structure. Item total correlations of subdimensions were r = .20-.68 and Cronbach's alpha coefficients were .77-.65. Test-retest correlations of the Adolescent Dysmenorrhea Self-Care Scale and its subdimensions were found r = .87-.99.
Conclusion: Turkish Adolescent Dysmenorrhea Self-Care Scale is a valid and reliable data collection tool consisting of 40 items and six subdimensions.
Race, ethnicity and postoperative pain in pediatric cancer patients: a single-institution retrospective study
Authors: Owusu-Agyemang Pascal , Feng Lei , Cata Juan P. 
Published: May 2023

BackgroundStudies have suggested racial and ethnic-based disparities in the intensity of postoperative pain experienced by patients. The objective of this study was to compare the peak and average post-anesthesia care unit (PACU) pain intensity scores of children of non-Hispanic (NH) White race to those of children of other racial/ethnic groups.MethodsSingle-institution retrospective study of children (≤18 years) who had undergone cancer-related surgical procedures from June 2016 through April 2022. Multivariable logistic regression was used to assess the association between race/ethnicity and the peak and average PACU pain intensity scores.ResultsOf the 1,009 unique patients, 74 (7.3%) were Asian, 93 (9.2%) were NH-Black, 310 (30.7%) were Hispanic/Latino, 51 (5.1%) identified as “Other” race (NH-Other), and 481 (47.7%) were NH-White. The median age [interquartile range (IQR)] was 13.7 years (IQR, 8.2–16.6), and 517 (51.2%) were female.In the multivariable analysis, the association between race/ethnicity and a peak PACU pain score greater than 3 was not significant (p = 0.062 for overall effect of race). However, upon comparing the peak PACU pain scores of children of other racial/ethnic groups to NH-White children, NH-Black children were 50.1% less likely than NH-White children to have a peak PACU pain score greater than 3 (odds ratio [OR], 0.499, 95% confidence interval [CI], 0.304–0.818; p = 0.006). Patient race/ethnicity was not associated with an average PACU pain score greater than 3 (p = 0.778).In the sub-group analysis of children who had undergone orthopedic or open abdominal surgeries, the proportions of children with peak and average PACU pain scores which were greater than 3 were not significantly different across racial/ethnic groups (p = 0.250 and p = 0.661, respectively).ConclusionsIn this retrospective study of children who had undergone cancer-related surgery, NH-Black children had significantly lesser odds than NH-White children of having a peak PACU pain score of moderate or severe intensity. However, in the sub-group analysis of children who had undergone orthopedic or open abdominal procedures, peak and average PACU pain scores were not significantly different across racial/ethnic groups.
Tensile energy dissipation and mechanical properties of the knee meniscus: relationship with fiber orientation, tissue layer, and water content
Authors: Morejon Andy , Dalbo Pedro L. , Best Thomas M. , Jackson Alicia R. , Travascio Francesco 
Published: May 2023

Introduction: The knee meniscus distributes and dampens mechanical loads. It is composed of water (∼70%) and a porous fibrous matrix (∼30%) with a central core that is reinforced by circumferential collagen fibers enclosed by mesh-like superficial tibial and femoral layers. Daily loading activities produce mechanical tensile loads which are transferred through and dissipated by the meniscus. Therefore, the objective of this study was to measure how tensile mechanical properties and extent of energy dissipation vary by tension direction, meniscal layer, and water content.Methods: The central regions of porcine meniscal pairs (n = 8) were cut into tensile samples (4.7 mm length, 2.1 mm width, and 0.356 mm thickness) from core, femoral and tibial components. Core samples were prepared parallel (circumferential) and perpendicular (radial) to the fibers. Tensile testing consisted of frequency sweeps (0.01–1Hz) followed by quasi-static loading to failure. Dynamic testing yielded energy dissipation (ED), complex modulus (E*), and phase shift (δ) while quasi-static tests yielded Young’s Modulus (E), ultimate tensile strength (UTS), and strain at UTS (εUTS). To investigate how ED is influenced by the specific mechanical parameters, linear regressions were performed. Correlations between sample water content (φw) and mechanical properties were investigated. A total of 64 samples were evaluated.Results: Dynamic tests showed that increasing loading frequency significantly reduced ED (p &lt; 0.05). Circumferential samples had higher ED, E*, E, and UTS than radial ones (p &lt; 0.001). Stiffness was highly correlated with ED (R2 &gt; 0.75, p &lt; 0.01). No differences were found between superficial and circumferential core layers. ED, E*, E, and UTS trended negatively with φw (p &lt; 0.05).Discussion: Energy dissipation, stiffness, and strength are highly dependent on loading direction. A significant amount of energy dissipation may be associated with time-dependent reorganization of matrix fibers. This is the first study to analyze the tensile dynamic properties and energy dissipation of the meniscus surface layers. Results provide new insights on the mechanics and function of meniscal tissue.
On a model-based approach to improve intranasal spray targeting for respiratory viral infections
Authors: Akash Mohammad Mehedi Hasan , Lao Yueying , Balivada Pallavi A. , Ato Phoebe , Ka Nogaye K. , Mituniewicz Austin , Silfen Zachary , Suman Julie D. , Chakravarty Arijit , Joseph-McCarthy Diane , Basu Saikat 
Published: May 2023

The nasopharynx, at the back of the nose, constitutes the dominant initial viral infection trigger zone along the upper respiratory tract. However, as per the standard recommended usage protocol (“Current Use”, or CU) for intranasal sprays, the nozzle should enter the nose almost vertically, resulting in sub-optimal nasopharyngeal drug deposition. Through the Large Eddy Simulation technique, this study has replicated airflow under standard breathing conditions with 15 and 30 L/min inhalation rates, passing through medical scan-based anatomically accurate human airway cavities. The small-scale airflow fluctuations were resolved through use of a sub-grid scale Kinetic Energy Transport Model. Intranasally sprayed droplet trajectories for different spray axis placement and orientation conditions were subsequently tracked via Lagrangian-based inert discrete phase simulations against the ambient inhaled airflow field. Finally, this study verified the computational projections for the upper airway drug deposition trends against representative physical experiments on sprayed delivery performed in a 3D-printed anatomic replica. The model-based exercise has revealed a new “Improved Use” (or, IU) spray usage protocol for viral infections. It entails pointing the spray bottle at a shallower angle (with an almost horizontal placement at the nostril), aiming slightly toward the cheeks. From the conically injected spray droplet simulations, we have summarily derived the following inferences: (a) droplets sized between 7–17 μm are relatively more efficient at directly reaching the nasopharynx via inhaled transport; and (b) with realistic droplet size distributions, as found in current over-the-counter spray products, the targeted drug delivery through the IU protocol outperforms CU by a remarkable 2 orders-of-magnitude.
Genesis and interaction of magmas at Nishinoshima volcano in the Ogasawara arc, western Pacific: new insights from submarine deposits of the 2020 explosive eruptions
Authors: Tamura Yoshihiko , Sato Tomoki , Ishizuka Osamu , McIntosh Iona M. , Yoshida Kenta , Maeno Fukashi , Chang Qing 
Published: May 2023

Sudden changes of eruption styles and magma compositions at arc volcanoes are enigmatic processes. Nishinoshima volcano, western Pacific, has had historical eruptions in 1973–1974 and from 2013 on and off to the present day. These eruptions were characterized by effusive Strombolian eruptions of andesite magmas until mid-June 2020, when they suddenly transitioned to violent explosive Strombolian eruptions that produced tephra fallout over a wide area. To understand this transition, we conducted marine surveys and sampling of the extensive submarine deposits of the tephra fallout. Our new data demonstrate that the full compositional range of the 2020 eruptions spans from basalt to dacite. We present evidence for magma mixing of newly injected basalt with andesite magmas. Nishinoshima consists of an andesitic main edifice surrounded by basaltic knolls: previous studies have shown that Nishinoshima andesite compositions can be generated by olivine fractionation of primary andesitic magmas that result from partial melting of hydrous mantle at relatively low pressures under the thin crust of the Ogasawara arc; knoll basalt compositions can be generated by partial melting of mantle at greater depths and were interpreted as older events of the volcano. We show that basalt magmas could have been generated throughout the entire history of Nishinoshima. In addition, we show that andesites from Nishinoshima and nearby Nishinoshima-Minami Knoll, which are only ∼8 km apart, have distinct subduction components. Together, these data improve our understanding of the diverse primary magmas responsible for the construction and continuing eruptive activity of an active island arc volcano.
The pathogenic p.Gln319Ter variant is not causing congenital adrenal hyperplasia when inherited in one of the duplicated CYP21A2 genes
Authors: Fanis Pavlos , Skordis Nicos , Toumba Meropi , Picolos Michalis , Tanteles George A. , Neocleous Vassos , Phylactou Leonidas A. 
Published: May 2023

ObjectiveThe study aimed to identify the pathogenic status of p.Gln319Ter (NM_000500.7: c.955C&gt;T) variant when inherited in a single CYP21A2 gene (bimodular RCCX haplotype) and to discriminate between a non-causing congenital adrenal hyperplasia (CAH) allele when inherited in a duplicated and functional CYP21A2 gene context (trimodular RCCX haplotype).Methods38 females and 8 males with hyperandrogenemia, previously screened by sequencing and identified as carriers for the pathogenic p.Gln319Ter, were herein tested by multiplex ligation-dependent probe amplification (MLPA) and a real-time PCR Copy number Variation (CNV) assay.ResultsBoth MLPA and real-time PCR CNV analyses confirmed a bimodular and pathogenic RCCX haplotype with a single CYP21A2 in 19/46 (41.30%) p.Gln319Ter carriers and who in parallel all shared elevated 17-OHP levels. The remaining 27 individuals that also carried the p.Gln319Ter exhibited low 17-OHP levels as a result of their carriership of a duplicated CYP21A2 with a trimodular RCCX haplotype. Interestingly, all of these individuals also carried in linkage disequilibrium with p.Gln319Ter two single nucleotide polymorphisms, the c.293-79G&gt;A (rs114414746) in intron 2 and the c.*12C&gt;T (rs150697472) in the 3’-UTR. Therefore, these variants can be used to distinguish between pathogenic and non-pathogenic genomic contexts of the c.955T (p.Gln319) in the genetic diagnosis of congenital adrenal hyperplasia (CAH).ConclusionThe employed methodologies identified a considerable number of individuals with non-pathogenic p.Gln319Ter from the individuals that typically carry the pathogenic p.Gln319Ter in a single CYP21A2. Therefore, it is extremely important the detection of such haplotypes for the prenatal diagnosis, treatment and genetic counseling in patients with CAH.
Clinical features and therapeutic outcomes of GH/TSH cosecreting pituitary adenomas: experience of a single pituitary center
Authors: Yu Na , Duan Lian , Hu Fang , Yang Shengmin , Liu Jie , Chen Meiping , Yao Yong , Deng Kan , Feng Feng , Lian Xin , Mao Xinxin , Zhu Huijuan 
Published: May 2023

BackgroundGrowth hormone (GH)/thyroid stimulating hormone (TSH) cosecreting pituitary adenoma (PA) is an exceedingly rare kind of bihormonal pituitary neuroendocrine tumors (PitNETs). Its clinical characteristics have rarely been reported.ObjectivesThis study aimed to summarize the clinical characteristics and experience of diagnosis and treatment among patients with mixed GH/TSH PAs from a single center.MethodsWe retrospectively reviewed GH/TSH cosecreting PAs from 2063 patients diagnosed with GH-secreting PAs admitted to Peking Union Medical College Hospital between January 1st, 2010, and August 30th, 2022, to investigate the clinical characteristics, hormone detection, imaging findings, treatment patterns and outcomes of follow-up. We further compared these mixed adenomas with age- and sex-matched cases of GH mono-secreting PAs (GHPAs). The data of the included subjects were collected using electronic records from the hospital’s information system.ResultsBased on the inclusion and exclusion criteria, 21 GH/TSH cosecreting PAs were included. The average age of symptom onset was 41.6 ± 14.9 years old, and delayed diagnosis occurred in 57.1% (12/21) of patients. Thyrotoxicosis was the most common complaint (10/21, 47.6%). The median inhibition rates of GH and TSH in octreotide suppression tests were 79.1% [68.8%, 82.0%] and 94.7% [88.2%, 97.0%], respectively. All these mixed PAs were macroadenomas, and 23.8% (5/21) of them were giant adenomas. Comprehensive treatment strategies comprised of two or more therapy methods were applied in 66.7% (14/21) of patients. Complete remission of both GH and TSH was accomplished in one-third of cases. In the comparison with the matched GHPA subjects, the mixed GH/TSH group presented with a higher maximum diameter of the tumor (24.0 [15.0, 36.0] mm vs. 14.7 [10.8, 23.0] mm, P = 0.005), a greater incidence of cavernous sinus invasion (57.1% vs. 23.8%, P = 0.009) and a greater difficulty of long-term remission (28.6% vs. 71.4%, P &lt;0.001). In addition, higher occurrence rates of arrhythmia (28.6% vs. 2.4%, P = 0.004), heart enlargement (33.3% vs. 4.8%, P = 0.005) and osteopenia/osteoporosis (33.3% vs. 2.4%, P = 0.001) were observed in the mixed PA group.ConclusionThere are great challenges in the treatment and management of GH/TSH cosecreting PA. Early diagnosis, multidisciplinary therapy and careful follow-up are required to improve the prognosis of this bihormonal PA.