bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electroacupuncture facilitates the integration of a grafted TrkC‐modified mesenchymal stem cell‐derived neural network into transected spinal cord in rats via increasing neurotrophin‐3
Authors: Yang Yang , Xu Hao‐Yu , Deng Qing‐Wen , Wu Guo‐Hui , Zeng Xiang , Jin Hui , Wang Lai‐Jian , Lai Bi‐Qin , Li Ge , Ma Yuan‐Huan , Jiang Bin , Ruan Jing‐Wen , Wang Ya‐Qiong , Ding Ying , Zeng Yuan‐Shan 
Published: March 2021

AbstractAimsThis study was aimed to investigate whether electroacupuncture (EA) would increase the secretion of neurotrophin‐3 (NT‐3) from injured spinal cord tissue, and, if so, whether the increased NT‐3 would promote the survival, differentiation, and migration of grafted tyrosine kinase C (TrkC)‐modified mesenchymal stem cell (MSC)‐derived neural network cells. We next sought to determine if the latter would integrate with the host spinal cord neural circuit to improve the neurological function of injured spinal cord.MethodsAfter NT‐3‐modified Schwann cells (SCs) and TrkC‐modified MSCs were co‐cultured in a gelatin sponge scaffold for 14 days, the MSCs differentiated into neuron‐like cells that formed a MSC‐derived neural network (MN) implant. On this basis, we combined the MN implantation with EA in a rat model of spinal cord injury (SCI) and performed immunohistochemical staining, neural tracing, electrophysiology, and behavioral testing after 8 weeks.ResultsElectroacupuncture application enhanced the production of endogenous NT‐3 in damaged spinal cord tissues. The increase in local NT‐3 production promoted the survival, migration, and maintenance of the grafted MN, which expressed NT‐3 high‐affinity TrkC. The combination of MN implantation and EA application improved cortical motor‐evoked potential relay and facilitated the locomotor performance of the paralyzed hindlimb compared with those of controls. These results suggest that the MN was better integrated into the host spinal cord neural network after EA treatment compared with control treatment.ConclusionsElectroacupuncture as an adjuvant therapy for TrkC‐modified MSC‐derived MN, acted by increasing the local production of NT‐3, which accelerated neural network reconstruction and restoration of spinal cord function following SCI.
Cardiovascular effects of sodium‐glucose co‐transporter‐2 inhibitors and glucagon‐like peptide‐1 receptor agonists: The P value and beyond
Authors: Kloecker David E. , Davies Melanie J. , Khunti Kamlesh , Zaccardi Francesco 
Published: March 2021

AbstractDespite growing awareness of the dangers of a dichotomous interpretation of trial results based on the ‘statistical significance’ of a treatment effect, the uptake of new approaches has been slow in diabetes medicine. We showcase a number of ways to interpret the evidence for a treatment effect applied to the cardiovascular outcome trials of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) and sodium‐glucose co‐transporter‐2 inhibitors (SGLT‐2is): the P value function (or confidence curves), which depicts the treatment effect across the whole spectrum of confidence levels; the counternull value, which is the hazard ratio (i.e. treatment effect size) supported by the same amount of evidence as the null value (i.e. no treatment effect); and the S value, which quantifies the strength of the evidence against the null hypothesis in terms of the number of coin tosses yielding the same side. We show how this approach identifies potential treatment effects, highlights similarities among trials straddling the threshold of statistical significance, and quantifies differences in the strength of the evidence from trials reporting statistically significant results. For example, while REWIND, CANVAS and CREDENCE failed to reach statistical significance at the .05 level for all‐cause mortality, their counternull values indicate that reduced death rates by 19%, 24% and 31%, respectively, are supported by the same amount of evidence as that indicating no treatment effect. Moreover, similarities among results emerge in trials of GLP‐1RAs (REWIND, EXSCEL and LEADER) lying closely around the threshold of ‘statistical significance’. Lastly, several S values, such as for the primary outcome in HARMONY Outcomes (S value 10.9) and all‐cause death in EMPAREG‐OUTCOME (S value 15.0), stand out compared with values for other outcomes and other trials, suggesting much larger differences in the evidence between these studies and several others that cluster around the .05 significance threshold. P value functions, counternull values and S values should complement the standard reporting of the treatment effect to help interpret clinical trials and make decisions among competing glucose‐lowering medications.
Subclinical left ventricular dysfunction in men under androgen deprivation therapy for prostate cancer, revealed by speckle‐tracking‐derived parameters, repolarization, and myocardial injury markers
Authors: Gheorghe Andrei C. D. , Ciobanu Ana , Hodorogea Andreea S. , Radavoi George D. , Jinga Viorel , Rascu Alexandru S. C. , Nanea Ioan T. , Gheorghe Gabriela S. 
Published: March 2021

AbstractObjectiveTo analyze global left ventricular longitudinal strain (GLS), mechanical dispersion (MD), electrocardiographic repolarization, and myocardial injury markers changes during androgen deprivation therapy (ADT) and subsequent hypogonadism in men with advanced prostate cancer.MethodsWe included 31 patients 69.7 ± 7.3 years old, in sinus rhythm, with stable cardiac conditions and evaluated them by echocardiography, electrocardiography, and blood sampling for high sensitivity cardiac troponin I (hs‐cTnI), and N‐terminal pro‐brain natriuretic peptide (NTproBNP), at ADT initiation (M0) and after 6 months of treatment (M1). Peak longitudinal strain by speckle‐tracking echocardiography was assessed in 17 left ventricular segments and averaged to GLS. Standard deviation of time intervals from the start of Q/R on electrocardiogram to peak longitudinal strain in the 17 segments (MDSD), and the difference between the longest and shortest time‐to‐peak strain intervals (MDdelta) were calculated as indices of MD. Fridericia corrected electrocardiographic repolarization parameters were analyzed as follows: QT interval (QTc), mean and maximum values of Tpeak‐Tend interval (Tpe), and Tpe/QT ratio, Tpe dispersion (Tped).ResultsSignificant impairments of the following parameters were registered between M0 and M1: GLS (%) (−16.93 ± 3.89; −14.43 ± 3.57, P < .001), MDSD (ms) (77.4 ± 21.4; 89 ± 27, P = .004), MDdelta (ms) (225.3 ± 78.3; 259.9 ± 108.4, P = .02), QTc (ms) (458.8 ± 43.4; 485.6 ± 45.1, P = .01), maxTpe/QT (0.246 ± 0.04; 0.268 ± 0.04, P = .01), maxTpe (ms) (105.4 ± 23.2; 119.5 ± 26.4 P = .01), meanTpe (ms) (83.3 ± 16.8; 90.7 ± 19.3, P = .02), and hs‐cTnI (ng/mL) (4.6 ± 5.4; 5.4 ± 6.4, P = .01). Mean serum testosterone level at M1 was 0.1 ± 0.13 ng/mL. The patients’ clinical cardiological status remained stable during follow‐up.ConclusionsADT and subsequent hypogonadism induce subclinical alterations in GLS, MD, electrocardiographic repolarization parameters, and hs‐cTnI during the first 6 months of treatment.
Topological structure of a tritrophic network composed of host plants, gall‐inducing insects and parasitoids in a restinga area in Brazil
Authors: de Araújo Walter Santos , Maia Valéria Cid 
Published: March 2021

AbstractPlants, insect herbivores and parasitoids can form tritrophic networks that are species rich and complex in interactions. In the present study, we describe the network structure of an assemblage composed of host plants, cecidomyiid gall midges and hymenopteran parasitoids in a restinga in Brazil. We used data collected between 1992 and 2011 to build plant‐galling and galling‐parasitoid networks. In total we recorded 44 species of host plants, 79 species of gall midges and 70 taxa of parasitoids. The network of host plants and gall midges was very specialized, being characterized by 79 distinct interactions, low connectance, low linkage density and high modularity. This specialized pattern is because all species of gall midges have been monophages. In contrast, galling‐parasitoid interactions were more numerous (203 distinct interactions) and were more connected, and less modular than expected based on the null model. The occurrence of generalist parasitoids (i.e. 35.7% of parasitoid species occurring on two or more hosts) is the main factor that explains this lower specialization in the galling‐parasitoid network when compared to the plant‐galling network. Our findings corroborate previous studies indicating high specialization for the interactions of gall midges with their plants but indicate a slightly smaller specialization of the parasitoids in relation to the gall midge species.
Systematic investigation of PRMT6 substrate recognition reveals broad specificity with a preference for an RG motif or basic and bulky residues
Authors: Hamey Joshua J. , Rakow Sinja , Bouchard Caroline , Senst Johanna M. , Kolb Peter , Bauer Uta‐Maria , Wilkins Marc R. , Hart‐Smith Gene 
Published: March 2021

Protein arginine methyltransferase 6 (PRMT6) catalyses the asymmetric dimethylation of arginines on numerous substrate proteins within the human cell. In particular, PRMT6 methylates histone H3 arginine 2 (H3R2) which affects both gene repression and activation. However, the substrate specificity of PRMT6 has not been comprehensively analysed. Here, we systematically characterise the substrate recognition motif of PRMT6, finding that it has broad specificity and recognises the RG motif. Working with a H3 tail peptide as a template, on which we made 204 amino acid substitutions, we use targeted mass spectrometry to measure their effect on PRMT6 in vitro activity. We first show that PRMT6 methylates R2 and R8 in the H3 peptide, although H3R8 is methylated with lower efficiency and is not an in vivo PRMT6 substrate. We then quantify the effect of 194 of these amino acid substitutions on methylation at both H3R2 and H3R8. In both cases, we find that PRMT6 tolerates essentially any amino acid substitution in the H3 peptide, but that positively charged and bulky residues are preferred near the target arginine. We show that PRMT6 also has preference for glycine, but only in the position immediately following the target arginine. This indicates that PRMT6 recognises the RG motif rather than the RGG motif. We further confirm this preference for the RG motif on another PRMT6 substrate, histone H4R3. This broad specificity and recognition of RG rather than RGG are distinctive among the PRMT family and has implications for the development of drugs to selectively target PRMT6.DatabasesPanorama Public (https://panoramaweb.org/PRMT6motif.url); ProteomeXchange (PXD016711).
Effect of different accessory devices on the dose delivered from pressurised metred‐dose inhalers
Authors: Nicola Mina , Hussein Raghda R. S. , Soliman Youssef M. A. , Abdelrahim Mohamed 
Published: March 2021

AbstractIntroductionsImproved aerosol delivery of bronchodilators to chronic obstructive pulmonary disease (COPD) subjects is a cornerstone in the treatment approach. Drug delivery and response are improved with the use of accessory devices [spacers and valved holding chambers (VHCs)] with metred‐dose inhalers (pMDIs). However, different accessory devices are available in the market with different properties that could affect aerosol delivery. Thus, this study aimed to assess the relative lung deposition and systemic bioavailability and compare bronchodilator response of salbutamol delivered using different accessory devices attached to pMDIs.MethodsTwelve healthy subjects and twelve COPD subjects inhaled 300 μg salbutamol (3 pMDI puffs) using five different accessory devices with either masks or mouthpieces (Able, Aerochamber plus flow Vu, Dolphin chamber, Tipshaler spacer, and modified Drink bottle spacer). Urine samples were collected thirty minutes post‐dosing and cumulatively for the next twenty‐four hours, to determine and compare the relative lung deposition [0‐0.5 hour excretion of urinary salbutamol (USAL0.5)] and systemic bioavailability [0.5‐24 hours excretion of urinary salbutamol (USAL24)] of salbutamol from the selected accessory devices. Also, the difference between pre and post‐inhalation forced expiratory volume in one second (ΔFEV1%) of predicted was determined for each accessory device.ResultsUrinary excretion of salbutamol (both USAL0.5 and USAL24 samples) in COPD subjects was significantly (P < .05) lower than in healthy subjects for all accessory devices. USAL0.5 and USAL24 in non‐antistatic spacers (modified Drink bottle spacer and Dolphin chamber spacers) were significantly lower (P < .05) than that for antistatic spacers (Aerochamber plus flow Vu, Able and Tips‐haler). No significant difference in USAL0.5 and USAL24 was observed between facemasks and mouthpieces.There was a significant difference (P < .05) in ΔFEV1% of predicted values between COPD subjects and healthy subjects. However, within the COPD group and the healthy group there was no significant difference in ΔFEV1% of predicted values between all accessory devices or between with mouthpiece or with a mask.ConclusionsCOPD subjects had lower aerosol delivered compared with healthy subjects. Anti‐static accessory devices delivered a higher amount of aerosol compared with non‐antistatic accessory devices. Even though the presence of a significant difference in aerosol delivery between non‐antistatic and antistatic accessory devices no significant difference was found in the ΔFEV1% between all accessory devices.
Prospective association between maternal bonding disorders and child toothbrushing frequency: A cross‐sectional study of the Japan Environment and Children’s Study
Authors: Tsuchiya Shinobu , Tsuchiya Masahiro , Momma Haruki , Nagatomi Ryoichi , Arima Takahiro , Yaegashi Nobuo , Igarashi Kaoru ,   the Japan Environment and Children’s Study Group
Published: March 2021

AbstractBackgroundDaily toothbrushing prevents early childhood caries, but reinforcement depends on facilitative parenting behaviours. Mother‐to‐infant bonding, the maternal affection towards the infant, is an environmental factor that strongly influences parenting.AimThis study examined the association between maternal bonding and children's daily toothbrushing frequency.DesignThe sample consisted of 83 954 mother‐infant pairs at two years postpartum, derived from the initial sample of JECS (cohort study), which included 104 062 foetuses. Maternal bonding disorders were assessed using the Mother‐to‐Infant Bonding Scale (MIBS). After multiple imputation for missing data, a multinomial logistic regression analysis was conducted with adjustments for several maternal (eg, age at delivery) and child‐related (eg, self‐performed toothbrushing) variables.ResultsThe odds ratio (95% confidence interval) for the association of maternal bonding disorders with the low (once per day) and the very low child toothbrushing frequency (<1 per day) was 1.12 (1.07‐1.17) and 1.23 (0.91‐1.66), respectively, after covariate adjustments. Furthermore, the univariate general linear model showed that the mean MIBS scores significantly decreased as the daily child toothbrushing frequency increased.ConclusionsThe prevalence of maternal bonding disorders at one year postpartum was prospectively associated with a lower frequency of child toothbrushing at two years of age.
The immunogenicity and safety of respiratory syncytial virus vaccines in development: A systematic review
Authors: Shan Jing , Britton Philip N. , King Catherine L. , Booy Robert 
Published: March 2021

AbstractBackgroundRespiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infection globally. There are vaccine candidates in development, but a systematic review on immunogenicity and safety of vaccine is lacking.MethodsThis systematic review of RSV vaccine clinical trials was undertaken using four databases. Searches were conducted using both controlled vocabulary terms such as “Respiratory Syncytial Virus, Human,” “Respiratory Syncytial Virus Infections,” “Respiratory Syncytial Virus Vaccines,” “Immunization,” “Immunization Programs” and “Vaccines” and corresponding text word terms. The included studies were limited to clinical trials published from January 2000 to 31 December 2020. RSV infection case was defined as RSV‐associated medically attended acute respiratory illness (MAARI) or RSV infection by serologically confirmed test (Western blot) during the RSV surveillance period. We calculated the relative risk of each vaccine trial with RSV infection case.ResultsOf 6306 publications, 38 were included and data were extracted covering four major types of RSV vaccine candidates, these being live‐attenuated/chimeric (n = 14), recombinant‐vector (n = 6), subunit (n = 12) and nanoparticle vaccines (n = 6). For RSV infection cases, nine trials were involved and none of them showed a vaccine‐related increased MAARI during RSV surveillance season.ConclusionLID ∆M2‐2, MEDI M2‐2, RSVcps2 and LID/∆M2‐2 /1030s (live‐attenuated) were considered the most promising vaccine candidates in infant and children. In the elderly, a nanoparticle F vaccine candidate and Ad26.RSV.preF were considered as two potential effective vaccines. A promising maternal vaccine candidate is still lacking.
Nondermatophyte mould onychomycosis
Authors: Gupta A.K. , Summerbell R.C. , Venkataraman M. , Quinlan E.M. 
Published: March 2021

AbstractNondermatophyte moulds (NDMs) onychomycosis is often difficult to diagnose as NDMs have been considered contaminants of nails. There are several diagnostic methods used to identify NDMs, however, repeated laboratory isolation is recommended to validate pathogenicity. With NDM and mixed infection (dermatophytes plus NDM) onychomycosis on the rise, accurate clinical diagnosis along with mycological tests is recommended. Systemic antifungal agents such as itraconazole and terbinafine (e.g. pulse regimen: 1 pulse = every day for one week, followed by no treatment for three weeks) have shown efficacy in treating onychomycosis caused by various NDMs such as Aspergillus spp., Fusarium spp., Scopulariopsis brevicaulis, and Onychocola canadensis. Studies investigating topical therapy and devices for NDM onychomycosis are limited. The emergence of antifungal resistance necessitates the incorporation of antifungal susceptibility testing into diagnosis when possible, for the management of recalcitrant infections. Case studies documented in the literature show newer azoles such as posaconazole and voriconazole as sometimes effective in treating resistant NDM onychomycosis. Treatment with broad‐spectrum antifungal agents (e.g. itraconazole and efinaconazole) and other combination therapy (oral + oral and/or oral + topical) may be considerations in the management of NDM onychomycosis.
Impact of occlusal force on decline in body mass index among older Japanese adults: Finding from the SONIC study
Authors: Fukutake Motoyoshi , Takahashi Toshihito , Gondo Yasuyuki , Kamide Kei , Masui Yukie , Matsuda Ken‐ichi , Enoki Kaori , Takeshita Hajime , Mihara Yusuke , Hatta Kodai , Sato Hitomi , Murotani Yuki , Hagino Hiromasa , Kabayama Mai , Ishizaki Tatsuro , Sugimoto Ken , Rakugi Hiromi , Maeda Yoshinobu , Moynihan Paula , Ikebe Kazunori 
Published: March 2021

AbstractObjectivesTo determine any independent influence of occlusal force and of number of natural teeth on decline in body mass index (BMI) among older Japanese adults.DesignLongitudinal study over a 3‐ to 6‐year period.SettingUrban and rural area in Japan.ParticipantsIndependently living Japanese adults aged 69–71 years and 79–81 years at baseline. This analysis excluded participants who were defined as underweight at baseline.MeasurementsInformation was collected on age, gender, occlusal force, the number of teeth, BMI, socioeconomic factors, medical history, the number of daily prescription medications, cognitive function, depressive symptoms, hand grip strength, and physical function. Maximal occlusal force was measured with a pressure‐sensitive sheet. Nutritional status was assessed using BMI, and participants with BMI <21.5 were defined as underweight. Then, they were divided into two groups: a “BMI declined” group who were defined as underweight at either 3‐ or 6‐year follow‐up survey, and a “BMI maintained” group who were not defined as underweight at both follow‐up surveys. Logistic generalized estimating equation (GEE) models were used to assess the effect of occlusal force and the number of teeth at baseline on decline in BMI over 3 or 6 years, after adjusting for possible covariates associated with nutritional status.ResultsThe final analysis included 704 participants. Eighty‐six (12.2%) participants were classified into the BMI declined group. Logistic GEE models showed that the number of teeth was not significantly associated with decline in BMI. However, occlusal force was significantly associated with decline in BMI (odds ratio = 0.90, 95% confidence interval = 0.83–0.97) after adjusting for covariates.ConclusionParticipants with lower occlusal force were more likely to be in the BMI less than 21.5 kg/m2. The findings suggest that to prevent decline in oral function is important to maintain nutritional status.
Impact of humate substances and Bacillus subtilis PB6 on thyroid activity and histomorphometry, iron profile and blood haematology of quail
Authors: Elnesr Shaaban S. , Abdel‐Razik Abdel‐Razik H. , Elwan Hamada A. M. 
Published: March 2021

AbstractThe purpose of this study was to assess the effects of dietary humate substances (HS) and CloSTAT (Bacillus subtilis PB6) on the thyroid activity and histology, iron profile, blood haematology and performance of growing Japanese quail. A total of 216 unsexed 7‐day‐old quail chicks were randomly assigned to six groups. The first group was fed a basal diet (BD) without any additives (control); the 2nd group received BD plus 0.05% CloSTAT, the 3rd and 4th groups were given BD plus 0.4% and 0.8% HS, respectively; and the 5th and 6th groups were administered BD plus CloSTAT + 0.4% HS and BD plus CloSTAT + 0.8% HS, respectively. The results showed that the growth performance was improved with the addition of CloSTAT alone or in combination with 0.4% HS compared with the control. Haematological parameters, iron level and transferrin saturation % were significantly (p < 0.001) increased by feeding HS compared with the control group. Serum thyroxin and triiodothyronine levels were significantly (p = 0.001) increased by adding CloSTAT relative to the control. Supplementation of 0.8% HS caused deterioration in histomorphometry parameters of the thyroid gland, but these parameters were improved in response to CloSTAT compared with the control. In conclusion, dietary B. subtilis PB6 as CloSTAT or CloSTAT + 0.4% HS supplementation may be efficacious in enhancing the growth performance and boosting the thyroid activity of growing Japanese quail. Moreover, the addition of 0.4% or 0.8% HS to quail diets boosted their iron profile and haematological parameters.