bluuebunny/crossref_metadata_2025_split huggingface dataset:
Muscle microRNAs in the cerebrospinal fluid predict clinical response to nusinersen therapy in type II and type III spinal muscular atrophy patients
Authors: Magen Iddo , Aharoni Sharon , Yacovzada Nancy Sarah , Tokatly Latzer Itay , Alves Christiano R. R. , Sagi Liora , Fattal‐Valevski Aviva , Swoboda Kathryn J. , Katz Jacob , Bruckheimer Elchanan , Nevo Yoram , Hornstein Eran 
Published: May 2022

AbstractBackground and purposeThe antisense oligonucleotide nusinersen (Spinraza) regulates splicing of the survival motor neuron 2 (SMN2) messenger RNA to increase SMN protein expression. Nusinersen has improved ventilator‐free survival and motor function outcomes in infantile onset forms of spinal muscular atrophy (SMA), treated early in the course of the disease. However, the response in later onset forms of SMA is highly variable and dependent on symptom severity and disease duration at treatment initiation. Therefore, we aimed to identify novel noninvasive biomarkers that could predict the response to nusinersen in type II and III SMA patients.MethodsThirty‐four SMA patients were included. We applied next generation sequencing to identify microRNAs in the cerebrospinal fluid (CSF) as candidate biomarkers predicting response to nusinersen. Hammersmith Functional Motor Scale Expanded (HFMSE) was conducted at baseline and 6 months after initiation of nusinersen therapy to assess motor function. Patients changing by ≥3 or ≤0 points in the HFMSE total score were considered to be responders or nonresponders, respectively.ResultsLower baseline levels of two muscle microRNAs (miR‐206 and miR‐133a‐3p), alone or in combination, predicted the clinical response to nusinersen after 6 months of therapy. Moreover, miR‐206 levels were inversely correlated with the HFMSE score.ConclusionsLower miR‐206 and miR‐133a‐3p in the CSF predict more robust clinical response to nusinersen treatment in later onset SMA patients. These novel findings have high clinical relevance for identifying early treatment response to nusinersen in later onset SMA patients and call for testing the ability of miRNAs to predict more sustained long‐term benefit.
Inhibitory effects of fluoxetine and duloxetine on the pharmacokinetics of metoprolol in vivo and in vitro
Authors: Xu Tao , Gao Nanyong , Li Yinghui , Wang Ru , Chen Bingbing , Hu Guoxin , Zhang Xiaodan 
Published: May 2022

AbstractDepression is common among people with cardiovascular diseases. Therefore, the combined use of antidepressants and cardiovascular drugs is very common, which increases the possibility of drug interaction. Simultaneously compare the effects of duloxetine and fluoxetine on metoprolol metabolism, and provide evidence‐based guidance for medication safety. Sprague–Dawley rats were randomly divided into three groups: group A (10.3 mg/kg metoprolol alone), group B (10.3 mg/kg metoprolol + 6.2 mg/kg fluoxetine), and group C (10.3 mg/kg metoprolol + 6.2 mg/kg duloxetine). Tail vein blood was collected and subjected to the ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC‐MS/MS) detection. Moreover, in vitro inhibition of fluoxetine and duloxetine were assessed by incubating liver microsomes and CYP2D6.1 with metoprolol. In in vivo study, the administration of fluoxetine or duloxetine significantly increased the AUC(0−𝑡) and AUC(0−∞) of metoprolol (P < 0.05). Differences between fluoxetine and duloxetine in plasma concentration were also investigated, and their pharmacokinetic parameters such as AUC(0−𝑡) and AUC(0−∞) were significantly distinct (P < 0.05). In vitro, fluoxetine and duloxetine inhibited the metabolism of metoprolol via mixed competitive mechanism of cytochrome P450. IC50 values of fluoxetine and duloxetine were 12.86 and 2.51 μM, respectively. Moreover, the metabolism rate of metoprolol was inhibited to 19.62% and 17.14% in recombinant human CYP2D6.1 by fluoxetine and duloxetine, respectively. Duloxetine showed a more significant inhibitory potential compared to fluoxetine in vitro, but the main pharmacokinetic parameters of fluoxetine and duloxetine revealed differences in inhibiting metoprolol metabolism in vivo.
Global synthesis reveals strong multifaceted effects of eucalypts on soils
Authors: Mallen‐Cooper Max , Atkinson Joe , Xirocostas Zoe A. , Wijas Baptiste , Chiarenza Giancarlo M. , Dadzie Frederick A. , Eldridge David J. 
Published: May 2022

AbstractAimEucalypts have a widespread global distribution owing to their popularity for agroforestry and as environmental plantings. Despite an abundance of site‐specific evidence that eucalypts modify soils and soil processes, we lack a quantitative synthesis of their overall effects at the global scale. This limits our capacity to assess the likely impacts of future introductions in any given region of the world.LocationGlobal.Time period1986–2021.Major taxa studiedEucalyptus, Angophora and Corymbia.MethodsWe used a systematic search to derive a database of empirical data from 227 studies across 33 countries (neffect size = 2,806) and tested three predictions about the effects of eucalypts on soil properties and whether these effects varied with plantation age and soil depth.ResultsCompared with (non‐eucalypt) native vegetation, eucalypts significantly reduced soil moisture, microbial abundance, nitrogen, cations and anions. Relative reductions in soil microbes and ions were stronger in older eucalypt plantations. A comparison of eucalypts with (non‐eucalypt) silvicultural and agropastoral systems revealed similar effects on most soil properties, although eucalypts tended to reduce potassium and enhance carbon to a greater extent than other managed systems. We found no consistent effects of eucalypts on soil pH.Main conclusionsOur study provides the first extensive global meta‐analysis of the effects of eucalypts on soil properties and processes and demonstrates that effects are highly dependent on the community with which they are compared (i.e., natural or managed). In general, our findings reinforce the widely held belief that eucalypts deplete soil nutrients and dominate water resources. Understanding how eucalypts affect soils allows us to assess their global suitability for agroforestry, soil rehabilitation and soil carbon enhancement, while considering the potential environmental costs.
Interventions for preventing keratinocytic cancer in patients with a history of a previous keratinocytic carcinoma: A systematic review
Authors: García‐Alonso María José , Peralta‐Pedrero María Luisa , Jurado‐Santa Cruz Fermín , Morales‐Sánchez Martha Alejandra 
Published: May 2022

AbstractKeratinocyte cancer (KC) is the most common cancer worldwide. It is important to analyze the actual interventions that are available for the prevention of patients with a previous history of a KC. We aim to review the existent literature to assess the efficacy and safety of interventions to prevent KC in patients with a history of previous KC. We searched clinical trials in which the main outcome was the prevention of KC in patients with a previous history of KC using the strategy published in the International Prospective Register of Systematic Reviews (PROSPERO registry), CRD42016045981. We analyzed 18 clinical trials from which eight reported a benefit with their respective intervention but had methodological flaws and a variable risk of bias. Two clinical trials (regarding celecoxib and oral supplementation with nicotinamide) seemed to have the most beneficial results reducing the incidence of KC in treated groups. However, all of the studies are highly heterogeneous, which does not allow a meta‐analysis to be performed. New studies with greater epidemiological value should be conducted.
In‐vitro digestibility, textural and quality characteristics of ditalini pasta fortified with green banana flour and its type ‐IV modified starch
Authors: Keran David Amelia , Kumar Paramasivam Suresh , Pushpavalli Subramaniyan , Uma Subbaraya 
Published: May 2022

SummaryResistant starch in unripe banana offers a possibility to alter the glycemic properties in convenience foods, such as pasta. In this study, pasta formulations were tried by replacing 30% semolina with varying proportions of green banana flour (GBF) and banana‐modified starch (MS). The effect of substitution on physicochemical and functional properties, including in‐vitro starch digestibility, antioxidant property and consumer acceptability, was evaluated. Among the composite flours, MS recorded higher swelling power and water holding capacity. The replacement of semolina with GBF resulted in higher resistant starch, 4–5 times enhanced indigestible fraction, phenols, flavonoids and antioxidant activity in pasta. Pronounced increment was also observed in potassium, calcium and magnesium content in blended pasta. Optimal cooking time was reduced with the addition of GBF, whereas it was enhanced with MS. GBF and MS in the blends, decreased the hydrolysis rate (up to 24%) and glycemic index (up to 17%) of pasta. However, the addition of MS beyond 10% negatively influenced springiness and chewiness. Microstructural studies explained the positive structural changes with the addition of GBF and MS. Sensory attributes disclosed that the addition of 25% GBF and 5% MS is a desirable proportion for pasta with a functional characteristics.
Nutrient release and antioxidant properties of functional sesame paste formulated with flaxseed during in vitro digestion
Authors: Zhang Yujin , Hou Lixia , Wang Xuede 
Published: May 2022

SummaryThis study aimed to investigate the structure, fatty acids and protein release and antioxidant activities of sesame paste (SP) formulated with flaxseed during in vitro gastrointestinal digestion and compared with SP and flaxseed paste (FP). The ratio of n‐3/n‐6 polyunsaturated fatty acid of flaxseed–sesame paste (FSP) was 0.26, which was significantly higher than that of SP (0.01). After digestion, SP contained the most abundant free linoleic acid, while the highest concentration of free linolenic acid was detected in FP. Interestingly, more soluble peptides with a molecular weight lower than 14.4 kDa were distributed in FP after gastric digestion. Meanwhile, after intestinal digestion, the hydrophilic fractions of FP showed the highest DPPH radical scavenging capacity, while the hydrophilic fractions of FP were the lowest than SP and FSP. These findings suggested that SP formulated with flaxseed as a functional ingredient could be a feasible way to increase the nutritional value of SP.
Rice bran and its constituents: Introduction and potential food uses
Authors: Eng Hui Yi , Mohd Rozalli Norazatul Hanim 
Published: May 2022

SummaryRice bran (RB) is one of the by‐products during the milling of rice. RB is underutilised due to its ease of susceptibility towards enzymatic activity. RB contains various bioactive compounds such as γ‐oryzanol, phytosterols, tocols and squalene. High nutritional properties make RB, and its constituents play their different roles in the food industry, such as gluten flour substitutes, alternate shortening, organogelators, stabilisers and other types of additives. This review will briefly introduce the RB and its constituents and discuss their potential applications in the food industry.
Insight into the mechanism of the quality improvement of porcine after ultrasound‐assisted immersion freezing
Authors: Li Junguang , Ma Xuyang , Zhang Jiawen , Wang Yu , Du Manting , Xiang Qisen , Wang Yuntao , Du Juan , Li Ke , Bai Yanhong 
Published: May 2022

SummaryThe influences of ultrasound‐assisted immersion freezing (UIF) at different power density levels (15, 30, 45 W L−1) on the quality characteristics of porcine M. longissimus lumborum were evaluated. The results showed that UIF was effective in inhibiting juice loss, enhancing tenderness along with colour stability of porcine, especially at UIF of 30 W L−1 (UIF‐30). This improvement induced by UIF was attributed to the rapid freezing rate, the reduction of freezable water content, the formation of tiny and even ice crystals and the maintenance of muscle fibre integrity. This study indicated UIF with appropriate density (UIF‐30) and was beneficial to improve the quality of pork muscle to the greatest extent.
The REinfection in COVID‐19 Estimation of Risk (RECOVER) study: Reinfection and serology dynamics in a cohort of Canadian healthcare workers
Authors: Racine Étienne , Boivin Guy , Longtin Yves , McCormack Deirdre , Decaluwe Hélène , Savard Patrice , Cheng Matthew P. , Hamelin Marie‐Ève , Carbonneau Julie , Tadount Fazia , Adams Kelsey , Bourdin Benoîte , Nantel Sabryna , Gilca Vladimir , Corbeil Jacques , De Serres Gaston , Quach‐Thanh Caroline 
Published: May 2022

AbstractBackgroundUnderstanding the immune response to natural infection by SARS‐CoV‐2 is key to pandemic management, especially in the current context of emerging variants. Uncertainty remains regarding the efficacy and duration of natural immunity against reinfection.MethodsWe conducted an observational prospective cohort study in Canadian healthcare workers (HCWs) with a history of PCR‐confirmed SARS‐CoV‐2 infection to (i) measure the average incidence rate of reinfection and (ii) describe the serological immune response to the primary infection.ResultsOur cohort comprised 569 HCWs; median duration of individual follow‐up was 371 days. We detected six cases of reinfection in absence of vaccination between August 21, 2020, and March 1, 2022, for a reinfection incidence rate of 4.0 per 100 person‐years. Median duration of seropositivity was 415 days in symptomatics at primary infection compared with 213 days in asymptomatics (p < 0.0001). Other characteristics associated with prolonged seropositivity for IgG against the spike protein included age over 55 years, obesity, and non‐Caucasian ethnicity.ConclusionsAmong unvaccinated healthcare workers, reinfection with SARS‐CoV‐2 following a primary infection remained rare.
Understanding the Water Resources of a Mountain‐block Aquifer: Tucson Mountains, Arizona
Authors: Eastoe Christopher J. , Beisner Kimberly R. 
Published: May 2022

AbstractWater resources are limited in arid locations such as Tucson Basin. Residential development in the Tucson Mountains to the west of Tucson, Arizona, is limited by groundwater resources. Groundwater samples were collected from fractured bedrock and alluvial aquifers surrounding the Tucson Mountains to assess water quality and recharge history through measurement of stable O, H, and S isotopes; tritium; and 14C. Most groundwater is a mixture of different ages but is commonly several thousand years old. A few sampling locations indicated a component of water recharged after the above‐ground nuclear testing of the mid 1950s, and these sites may represent locations near where the aquifer receives present‐day recharge. The Tucson Mountains also host sulfide deposits associated with fractures and replacement zones; these locally contribute to poor‐quality groundwater. Projections of future climate predict intensifying drought in southwestern North America. In the study area, a combination of strategies such as rainwater harvesting, exploitation of renewable water, and low groundwater use could be used for sustainable use of the groundwater supply.
Preliminary study on left bundle branch area pacing in children: Clinical observation of 12 cases
Authors: Wenlong Dai , Baojing Guo , Chencheng Dai , Jianzeng Dong 
Published: May 2022

AbstractIntroductionLeft bundle branch area pacing (LBBAP) maintains electrical and mechanical synchronization of the ventricles. It is a relatively physiological pacing mode, with low and stable pacing threshold and wider indications. LBBAP in children has been rarely reported.MethodsThis study observed 12 children attempted LBBAP from January 2019 to January 2021 in the department of pediatric cardiology of Anzhen Hospital prospectively. Clinical data, pacing parameters, electrocardiograms, intracardiac electrograms, echocardiographic measurements and complications were recorded at implant and during follow‐up.ResultsThe 12 patients aged between 3 and 14 years old and weighted from 13 to 48 kg. Eleven patients were diagnosed with third‐degree atrioventricular block and 1 patient (case 4) suffered from cardiac dysfunction due to right ventricular apical pacing (RVAP). Left bundle branch area pacing was successfully achieved in all patients with narrow QRS complexes and V1 lead showed changes like right bundle branch block in the pacing electrocardiogram. Left ventricular ejection fraction in case 4 recovered on the 3rd day after LBBAP. The median of left ventricular end diastolic diameter Z score of the 12 patients decreased from 1.75 to 1.05 3 months after implantation (p < 0.05). The median of paced QRS duration was 103 ms. The median of pacing threshold, R‐wave amplitude and impedance were 0.85 V, 15 mV and 717 Ω respectively and remained stable during follow‐up. No complications such as loss of capture, lead dislodgement or septal perforation occurred.ConclusionsLeft bundle branch area pacing can be performed safely in children with narrow QRS duration and stable pacing parameters. Cardiac dysfunction caused by long‐term RVAP can be corrected by LBBAP quickly.
In vivo porcine characterization of atrial lesion safety and efficacy utilizing a circular pulsed‐field ablation catheter including assessment of collateral damage to adjacent tissue in supratherapeutic ablation applications
Authors: Hsu Jonathan C. , Gibson Douglas , Banker Rajesh , Doshi Shephal K. , Gidney Brett , Gomez Tara , Berman Dror , Datta Keshava , Govari Assaf , Natale Andrea 
Published: May 2022

AbstractIntroductionPulsed‐field ablation (PFA), an ablative method that causes cell death by irreversible electroporation, has potential safety advantages over radiofrequency ablation and cryoablation. Pulmonary vein (PV) isolation was performed in a porcine model to characterize safety and performance of a novel, fully‐integrated biphasic PFA system comprising a multi‐channel generator, variable loop circular catheter, and integrated PFA mapping software module.MethodsEight healthy porcine subjects were included. To evaluate safety, multiple ablations were performed, including sites not generally targeted for therapeutic ablation, such as the right inferior PV lumen, right superior PV ostium, and adjacent to the esophagus and phrenic nerve. To evaluate the efficacy, animals were recovered, followed for 30(±3) days, then re‐mapped. Gross pathological and histopathological examinations assessed procedural injuries, chronic thrombosis, tissue ablation, penetration depth, healing, and inflammatory response.ResultsAll eight animals survived follow‐up. PV narrowing was not observed acutely nor at follow‐up, even when ablation was performed deep to the PV ostium. No injury was seen grossly or histologically in adjacent structures. All PVs were durably isolated, confirmed by bidirectional block at re‐map procedure. Histological examination showed complete, transmural necrosis around the circumference of the ablated section of right PVs.ConclusionThis preclinical evaluation of a fully‐integrated PFA system demonstrated effective and durable ablation of cardiac tissue and PV isolation without collateral damage to adjacent structures, even when ablation was performed in more extreme settings than those used therapeutically. Histological staining confirmed complete transmural cell necrosis around the circumference of the PV ostium at 30 days.
FOXO4 peptide targets myofibroblast ameliorates bleomycin‐induced pulmonary fibrosis in mice through ECM‐receptor interaction pathway
Authors: Han Xiaodan , Yuan Tong , Zhang Junling , Shi Yonggang , Li Deguan , Dong Yinping , Fan Saijun 
Published: May 2022

AbstractPulmonary fibrosis (PF) is a progressive interstitial lung disease with limited treatment options. The incidence and prevalence of PF is increasing with age, cell senescence has been proposed as a pathogenic driver, the clearance of senescent cells could improve lung function in PF. FOXO4‐D‐Retro‐Inverso (FOXO4‐DRI), a synthesis peptide, has been reported to selectively kill senescent cells in aged mice. However, it remains unknown if FOXO4‐DRI could clear senescent cells in PF and reverse this disease. In this study, we explored the effect of FOXO4‐DRI on bleomycin (BLM)‐induced PF mouse model. We found that similar as the approved medication Pirfenidone, FOXO4‐DRI decreased senescent cells, downregulated the expression of senescence‐associated secretory phenotype (SASP) and attenuated BLM‐induced morphological changes and collagen deposition. Furthermore, FOXO4‐DRI could increase the percentage of type 2 alveolar epithelial cells (AEC2) and fibroblasts, and decrease the myofibroblasts in bleomycin (BLM)‐induced PF mouse model. Compared with mouse and human lung fibroblast cell lines, FOXO4‐DRI is inclined to kill TGF‐β‐induced myofibroblast in vitro. The inhibited effect of FOXO4‐DRI on myofibroblast lead to a downregulation of extracellular matrix (ECM) receptor interaction pathway in BLM‐induced PF. Above all, FOXO4‐DRI ameliorates BLM‐induced PF in mouse and may be served as a viable therapeutic option for PF.
Current status of low‐density lipoprotein cholesterol for primary prevention of coronary artery disease in late‐stage elderly persons with type 2 diabetes mellitus: A retrospective, single‐center study
Authors: Yamamoto Yuki , Ito Jun , Ito Kei , Fujii Masanao , Nakajima Rikako , Saito Kazumi , Yagyu Hiroaki 
Published: May 2022

AbstractAims/IntroductionThe importance of low‐density lipoprotein cholesterol (LDL‐C) in the primary prevention of cardiovascular disease has recently been reported in the population aged ≥75 years with hypercholesterolemia. Therefore, the current status of LDL‐C management for primary prevention of coronary artery disease in patients aged ≥75 years with type 2 diabetes mellitus was investigated.Materials and MethodsA total of 124 patients aged ≥75 years who had type 2 diabetes mellitus, but no coronary artery disease, were investigated. The patients' background characteristics, LDL‐C, glycemic status, ankle‐brachial index and cardio‐ankle vascular index were compared between patients taking and not taking LDL‐C‐lowering agents, such as hydroxymethylglutaryl‐CoA reductase inhibitors (statins) and ezetimibe. The details of the antihyperlipidemic and antidiabetic agents used in the present study were also examined.ResultsLDL‐C was significantly lower in patients taking LDL‐C‐lowering agents (LDLCLT[+]) than in patients not taking them (LDLCLT[−]), although LDL‐C was maintained <120 mg/dL in both groups (93.0 mg/dL vs 102.1 mg/dL). Approximately half of the cases in the LDLCLT(+) group received moderate‐intensity statins, with pitavastatin being the most prescribed statin. Glycated hemoglobin was significantly lower in the LDLCLT(+) group than in the LDLCLT(−) group (6.9% vs 7.3%). Sodium‐glucose transporter 2 inhibitors were more frequently used in the LDLCLT(+) group than in the LDLCLT(−) group. The ankle‐brachial index/cardio‐ankle vascular index did not differ between the groups.ConclusionLow‐density lipoprotein cholesterol was properly managed for primary prevention of coronary artery disease in patients aged ≥75 years with type 2 diabetes mellitus regardless of the presence or absence of LDL‐C‐lowering agents.