bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mab-Mig: Registry of the Spanish Neurological Society of Erenumab for Migraine Prevention. Three-Months Results
Authors: Belvís Robert , Irimia Pablo , Pozo-Rosich Patricia , González-Oria Carmen , Cano Antonio , Viguera Javier , Sánchez Belén , Molina Francisco , Río Margarita Sánchez del , Beltran Isabel , Oterino Agustín , Cuadrado Elisa , Gómez-Camello Angel , Alberte-Woodward  , Jurado Carmen , Oms Teresa , Ezpeleta David , de Terán Javier Díaz , Morollón Noemi , Latorre Germán , Torres-Ferrús Marta , Alpuente Alicia , Lamas Raquel , Toledano Carlos , Leira Rogelio , Santos-Lasaosa Sonia 
Published: March 2021

Abstract
Background

Erenumab was approved in Europe for migraine prevention in patients with ≥4 monthly migraine days (MMD). In Spain, Novartis started a personalized managed access program which allowed free access to erenumab before official reimbursement. The Headache Study Group of the Spanish Neurological Society started a registry to monitor real-world safety and efficacy, and all Spanish headache experts were invited to participate.

Methods

Patients fulfilled ICHD3 criteria for migraine and had ≥ 4MMD. Sociodemographic and clinical data were registered as well as MMD, headache frequency (MHD), prior and concomitant preventive treatment, medication overuse headache (MOH), migraine evolution, adverse events, and PROs: HIT6, MIDAS, and PGIC. A >50% reduction of MMD after 3 months was considered as response.

Results

We included 210 patients (female 86.7%, mean age 46.4 years old) from 22 hospitals from February 2019 – to – June 2020. Most patients (89.5%) suffered from chronic migraine with a mean evolution of 8.6 years. MOH was present in 70% of patients, and 17.1% had migraine with aura. Average of prior preventive treatment failure was >7 (BoNT/A had been used by 95.2%). Most patients (67,6%) started with erenumab 70mg. 61% of patients were also taking oral preventive drugs or getting simultaneous BoNT/A (27.6%). Responder rate was 37.1% and the mean reduction of MMD was -6.28 and MHD: -8.6. Regarding PROs: MIDAS: -35 p., HIT6: -11.6 p., PIGC: 4.7 p. Predictors of good response were: HIT6 score ( p =0.01), prior preventive treatment failures ( p =0.026), absence of MOH ( p =0.039), and simultaneous BoNT/A treatment ( p <0.001). 20% had adverse event, but only two of them were severe (0.9%) which led to treatment discontinuation. Mild constipation was the most frequent adverse event (8.1%).

Conclusion

In real-life, in a personalized managed access program, erenumab shows a good profile of efficacy and an excellent safety in migraine prevention in our cohort of refractory patients.
Stress tolerance enhancement via SPT15 base editing in Saccharomyces cerevisiae
Authors: Liu Yanfang , Lin Yuping , Guo Yufeng , Wu Fengli , Zhang Yuanyuan , Qi Xianni , Wang Zhen , Wang Qin-Hong 
Published: March 2021

Abstract
Background
Saccharomyces cerevisiae is widely used in traditional brewing and modern fermentation industries to produce biofuels, chemicals and other bioproducts, but challenged by various harsh industrial conditions, such as hyperosmotic, thermal and ethanol stresses. Thus, its stress tolerance enhancement has been attracting broad interests. Recently, CRISPR/Cas-based genome editing technology offers unprecedented tools to explore genetic modifications and performance improvement of S. cerevisiae.
Results
Here, we presented that the Target-AID (activation-induced cytidine deaminase) base editor of enabling C-to-T substitutions could be harnessed to generate in situ nucleotide changes on the S. cerevisiae genome, thereby introducing protein point mutation in cells. The general transcription factor gene SPT15 was targeted, and total 36 mutants with diversified stress tolerances were obtained. Among them, the 18 tolerant mutants against hyperosmotic, thermal and ethanol stresses showed more than 1.5-fold increases of fermentation capacities. These mutations were mainly enriched at the N-terminal region and the convex surface of the saddle-shaped structure of Spt15. Comparative transcriptome analysis of three most stress-tolerant (A140G, P169A and R238K) and two most stress-sensitive (S118L and L214V) mutants revealed common and distinctive impacted global transcription reprogramming and transcriptional regulatory hubs in response to stresses, and these five amino acid changes had different effects on the interactions of Spt15 with DNA and other proteins in the RNA Polymerase II transcription machinery according to protein structure alignment analysis.
Conclusions
Taken together, our results demonstrated that the Target-AID base editor provided a powerful tool for targeted in situ mutagenesis in S. cerevisiae and more potential targets of Spt15 residues for enhancing yeast stress tolerance.
Nomogram-Based Prediction of the Risk of Macrosomia: A Prospective Cohort Study in a Chinese Population
Authors: Du Jing , Chai Sanbao , Zhao Xin , Sun Jianbin , Yuan Ning , Yu Xiaofeng , Zhang Qiaoling , Zhang Xiaomei 
Published: March 2021

Abstract
Objective: This study aimed to establish a nomogram for predicting the risk of macrosomia in early pregnancy.Methods: We performed a prospective cohort study involving 1,549 pregnant women. According to the birth weight of newborn, the subjects were divided into two groups: macrosomia group and non-macrosomia group. Multivariate logistic regression was used to analyze the risk factors for macrosomia.Results: The prevalence of macrosomia was 6.13% (95/1549) in our hospital. Multivariate logistic regression analysis showed the risk factors of macrosomia were prepregnancy overweight (OR: 2.126, 95% CI: 1.181-3.826)/obesity (OR: 3.536, 95% CI: 1.555-8.036), multiparity (OR:1.877, 95% CI: 1.160-3.039), the history of macrosomia (OR: 36.971, 95% CI: 19.903-68.674), the history of GDM/DM (OR: 2.285, 95% CI: 1.314-3.976), the higher levels of HbA1c (OR: 1.763, 95% CI: 1.004-3.097) and TC (OR: 1.360, 95% CI: 1.004-1.842). A nomogram was developed for predicting macrosomia based on maternal factors related to the risk of macrosomia in early pregnancy. The area under the receiver operating characteristic (ROC) curve of the nomogram was 0.807 (95% CI: 0.755–0.859), the sensitivity and specificity of the model were 0.716 and 0.777, respectively.Conclusion: The nomogram model provides an accurate mothed for clinicians to early predict macrosomia.
Electrical, Photoluminescence and Optical Investigation of ZnO Nanoparticles Sintered at Different Temperatures
Authors: Sedky Ahmed , Ali Atif , Somaily H.H , Algarni H 
Published: March 2021

Abstract
We report here structural, electrical, photoluminescence (PL), and optical investigations of ZnO nanoparticles. The ZnO samples are initially sintered at various temperatures (T s ) (600-1200 o C) temperatures and their size is reduced twice to nanoscale by using ball friction at 200 rpm rotational speed and 30 minutes duration. It is found that the T s do not influence the well-known peaks associated with the ZnO hexagonal structure, whereas the constants of the lattice and the average crystallite diameters are affected. Although the nonlinear area is observed for all samples in the I-V curves, the breakdown field E B and nonlinear coefficient β are moved to lower values as T s increases, while the residual voltage K r and nonlinear conductivity (σ 2 ) are increased. The empirical relations for K r , E B , and β as a function of T s are; K r = 0.004 T s – 0.487, E B = -1.786T s +2559.5 and β = -0.052 T s +75.19. On the other hand, a maximum UV absorption shift (A max ) is obtained at 412 nm, 400 nm, 384 nm, and 326 nm as the T s increases up to 1200 o C. For each sample, two different energy band gap values are obtained; the first is called the basic bandgap (E gh ) and its value above 3 eV, while the second is called the optical band gap (E gL ), and its value below 2.1 eV. Moreover, the empirical relations of them are E gh = 0.002 T s - 0.24, E gl = -0.0033 T s +5.242 and ∆E = - 0.0015 T s +5.002. Furthermore, the values of (N/m*) and lattice dielectric constant ε L are increased by increasing T s up to 1200 o C, while the vice is versa for the interatomic distance R. The dielectric loss tan δ is almost linear above 4 eV for all samples, and it decreases sharply as the T s increases. The optical and electrical conductivities σ opt and σ ele are decreased as the T s increases up to 1200 o C. Finally, the characteristic of UV band edges against the optimum value of PL intensity for the samples shows 8-continuous peaks. Furthermore, the PL intensity of the peaks is decreased by increasing T s and also by shifting the UV wave number towards the IR region.
Antibiotic drug resistance pattern of uropathogens seen in the first episode of community-acquired pediatric urinary tract infections at a tertiary care hospital
Authors: Sari Eyup , Yazilitas Fatma , Celebi Fatma Zehra Oztek , Akcaboy Meltem , Akisoglu Ozlem , Senel Saliha 
Published: March 2021

Abstract
BackgroundIncreased antibiotic resistance is a significant problem associated with higher morbidity, mortality, and costs in managing urinary tract infections (UTI). This study aims to analyze the antimicrobial resistance profile of uropathogens isolated from children with the first attack of community-acquired UTI.Materials and MethodsThis retrospective cohort study was conducted between January 2010-December 2016, with the patients aged one month to 18 years diagnosed with the first attack of community-acquired UTI at the pediatric outpatient clinic of a tertiary care hospital. Patients' age, sex, UTI history, clinical findings at admission, urine analysis, urine culture, and antibiogram results were recorded.ResultsA total of 1086 patients and 1086 cultures were included in the study. The male/female ratio was 1/5.3. The mean age of the children was 73.7±47.1 (0.4-215.9) months. 16.0% were aged 1-24 months. E. coli was the most common causative agent found to be 85.1% in frequency. The overall antimicrobial resistance was found to be highest for ampicillin, followed by piperacillin and trimethoprim-sulfamethoxazole (63.5, 41.6 and 38.1%, respectively). Imipenem, amikacin, and tobramycin had the least resistance (0.5, 0.5, and 7.6%, respectively). The overall antimicrobial resistance against amoxicillin-clavulanate, ampicillin-sulbactam, cefuroxime, ceftriaxone was 19.4, 24, 25.9 and 21.1%; respectively.Extended-spectrum beta-lactamase positivity was detected in 5.6% (n=61) of samples.ConclusionOur study showed significant increase in antimicrobial resistance to the most common antibiotics which are prescribed before urine culture results and antibiotic sensitivities are available. The resistance rates for amoxicillin-clavulanate, ampicillin-sulbactam, cefuroxime, ceftriaxone were almost 20% or above in children with the first UTI attack in an outpatient setting.
Quantized classical response from spectral winding topology
Authors: Li Linhu , Mu Sen , Lee Ching Hua , Gong Jiangbin 
Published: March 2021

Abstract
Topologically quantized response is one of the focal points of contemporary condensed matter
physics. While it directly results in quantized response coefficients in quantum systems, there
has been no notion of quantized response in classical systems thus far. This is because quantized
response has always been connected to topology via linear response theory that assumes a quantum
mechanical ground state. Yet, classical systems can carry arbitrarily amounts of energy in each mode,
even while possessing the same number of measurable edge modes as their topological winding. In
this work, we discover the totally new paradigm of quantized classical response, which is based on
the spectral winding number in the complex spectral plane, rather than the winding of eigenstates
in momentum space. Such quantized response is classical insofar as it applies to phenomenological
non-Hermitian setting, arises from fundamental mathematical properties of the Green’s function,
and shows up in steady-state response, without invoking a conventional linear response theory.
Speciﬁcally, the ratio of the change in one quantity depicting signal amplification to the variation
in one imaginary ﬂux-like parameter is found to display fascinating plateaus, with their quantized
values given by the spectral winding numbers as the topological invariants.
Neutralization of IL-33 Modifies the Type 2 and Type 3 Inflammatory Signature of Viral Induced Asthma Exacerbation.
Authors: Warren Kristi J , Poole Jill A , Sweeter Jenea M , DeVasure Jane M , Dickinson John D , Peebles R. Stokes , Wyatt Todd A 
Published: March 2021

Abstract
Background: Respiratory viral infections are one of the leading causes of need for emergency care and hospitalizations in asthmatic individuals, and airway-secreted cytokines are released within hours of viral infection to initiate these exacerbations. IL-33, specifically, contributes to these allergic exacerbations by amplifying type 2 inflammation. We hypothesized that blocking IL-33 in RSV-induced exacerbation would significantly reduce allergic inflammation. Methods: Sensitized BALB/c mice were challenged with aerosolized ovalbumin (OVA) to establish allergic inflammation, followed by RSV-A2 infection to yield four treatment groups: Saline only (Saline), RSV-infected alone (RSV), OVA alone (OVA), and OVA-treated with RSV infection (OVA-RSV). Lung outcomes included lung mRNA and protein markers of allergic inflammation, histology for mucus cell metaplasia and lung immune cell influx by cytospin and flow cytometry. Results: While thymic stromal lymphopoietin (TSLP) and IL-33 were detected 6 hours after RSV infection in the OVA-RSV mice, IL-23 protein was uniquely upregulated in RSV-infected mice alone. OVA-RSV animals varied from RSV- or OVA-treated mice as they had increased lung eosinophils, neutrophils, group 2 innate lymphoid cells (ILC2) and group 3 innate lymphoid cells (ILC3) detectable as early as 6 hours after RSV infection. Neutralized IL-33 significantly reduced ILC2 and eosinophils, and the prototypical allergic proteins, IL-5, IL-13, CCL17 and CCL22 in OVA-RSV mice. Numbers of neutrophils and ILC3 were also reduced with anti-IL-33 treatment in both RSV and OVA-RSV treated animals as well. Conclusions: Taken together, our findings indicate a broad reduction in allergic-proinflammatory events mediated by IL-33 in RSV-induced asthma exacerbation.
Phase II Study of Metronomic Treatment With Daily Oral Vinorelbine as First-line Chemotherapy in Patients With Advanced/metastatic HR+/HER2- Breast Cancer Resistant to Endocrine Therapy: VinoMetro – AGO-B-046
Authors: Krajnak Slavomir , Decker Thomas , Schollenberger Lukas , Rosé Christian , Ruckes Christian , Fehm Tanja , Thomssen Christoph , Harbeck Nadia , Schmidt Marcus 
Published: March 2021

Abstract
PurposeMetronomic chemotherapy (MCT) is an increasingly used treatment option in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced/metastatic breast cancer (MBC) after failure of endocrine-based therapies. MethodsVinoMetro was a multicentre, open-label, single-arm, phase II study of metronomic oral vinorelbine (VRL; 30 mg/day) as a first-line chemotherapy (CT) in patients with HR+/HER2- MBC after endocrine failure. The primary endpoint was the clinical benefit rate (CBR) at 24 weeks. ResultsBetween January 2017 and April 2019, 9 patients were enrolled. The CBR was 22.2% (90% confidence interval [CI] 4.1–55.0), p=0.211. The median progression-free survival (PFS) was 12.0 weeks (95% CI 11.3–12.7). Grade 3-4 adverse events (AEs) occurred in 22.2% of patients. One patient died of febrile neutropenia.ConclusionVinoMetro (AGO-B-046) was closed early after 9 patients and occurrence of one grade 5 toxicity in agreement with the lead institutional review board (IRB). Metronomic dosing of oral VRL in HR+/HER2- MBC as first-line CT after failure of endocrine therapies showed only limited benefit in this population.Trial registration number and date of registrationClinicalTrials.gov Identifier: NCT03007992; December 15, 2016
miR-142-3p and HMGB1 Are Negatively Regulated in Proliferation, Apoptosis, Migration and Autophagy of Cartilage Endplate Cells
Authors: Wang Bo , Ji Demin , Xing Wenhua , Li Feng , Huang Zhi , Zheng Wenkai , Xue Jianmin , Yang Xuejum , Zhu Yong 
Published: March 2021

Abstract
Background: cartilage endplate (CEP) degeneration plays a vital role in the pathological process of intervertebral disc degeneration. It has been previously reported that microRNAs may participate in the occurrence and development of intervertebral disc degeneration through regulating its’ target genes directly. The regulatory roles of miR-142-3p /HMGB1 in some orthopedic diseases have been determined successively, but there was no report about the degeneration of CEP. Therefore, we aimed to determine the regulation of miR-142-3p /HMGB1or potential molecular mechanisms on proliferation, apoptosis, migration, and autophagy of CEP cells.Methods: the target gene of miR-142-3p was determined by double luciferase assay. We selected ATDC5 cell lines. CCK-8 method was used to detect cell proliferation. Real-time fluorescence quantitative PCR was used to determine gene expression levels, and western blot analysis was used to determine protein expression levels. We chose the flow cytometry to measure cell apoptosis and cell cycle.Results: the result of luciferase detection showed that the target gene of miR-142-3p in CEP cells was HMGB1. Knockdown the miR-142-3p inhibited the expression level of HMGB1, the proliferation and migration of CEP cells, but it promoted apoptosis of CEP cells. In addition, the detection results of the proteins related to apoptosis or autophagy showed that knockdown of miR-142-3p promoted apoptosis and autophagy.Conclusion: The negative regulation of miR-142-3p /HMGB1 can affect the proliferation, apoptosis, migration, and autophagy of CEP cells. Our results provided a new idea for the targeted treatment of CEP degeneration by inhibiting the expression of HMGB1.
Marine fish larvae consistently use external cues for orientation
Authors: Berenshtein Igal , Faillettaz Robin , Irisson Jean-Olivier , Kiflawi Moshe , Siebeck Ulrike , Leis Jeffery , Paris Claire 
Published: March 2021

Abstract
The larval stage is the main dispersive mechanism of most marine teleost fish species. The degree to which larval behavior controls dispersal outcome has been a subject of debate in the past decades. Multiple studies demonstrated orientation mechanisms in several species separately, however a cross-species analysis examining fundamental orientation traits has not been carried out. Here, we apply a cross-species meta-analysis, focusing on the fundamental question of whether larval fish use external cues for directional movement. We compare the observed directional patterns to those expected under a strict use of internal cues. We find that the bulk of fish larvae use external cues for directional swimming, highlighting the contribution of larval orientation behavior to larval dispersal outcome. This finding is an essential step towards a proper implementation of larval behavior in biophysical dispersal models, improving our understanding of population connectivity, and facilitating sustainable management and conservation of marine resources.
Silencing Sirtuin5 induces DNA damage by suppressing the pentose phosphate pathway in a demalonylation-dependent manner: A possible target for anticancer therapy in CRC
Authors: Wang Hao-Lian , Chen Yan , Wang Yun-Qian , Tao En-Wei , Tan Juan , Liu Qian-Qian , Li Chun-Min , Tong Xuemei , Gao Qin-Yan , Hong Jie , Chen Ying-Xuan , Fang Jingyuan 
Published: March 2021

Abstract
A previous study by our research group showed that sirtuin5 (SIRT5), a member of the class III NAD＋-dependent deacetylase family, is highly expressed in colorectal cancer (CRC). The present study showed that deletion of SIRT5 induced cell cycle arrest and apoptosis as a result of continuous and irreparable DNA damage in CRC cells, a consequence of the impaired production of ribose-5-phosphate (R5P) which is essential for nucleotide synthesis. Consistently, the cell cycle arrest and apoptosis induced by SIRT5 silencing could be reversed by supplementation with four nucleotides. Moreover, metabolic profiling revealed that silencing of SIRT5 could inhibit the non-oxidative pentose phosphate pathway (PPP), which produces R5P, required for base ribosylation. Notably, SIRT5 activates transketolase (TKT), the key enzyme in the cellular non-oxidative PPP, by mediating its lysine demalonylation through the interaction between SIRT5 and TKT. Furthermore, the results demonstrated that TKT is essential for the SIRT5-induced malignant phenotypes of CRC, both in vivo and in vitro. These results therefore revealed that the increased lysine malonylation levels of TKT caused by silencing SIRT5 suppresses non-oxidative pentose phosphate metabolism, leading to a low-nucleotide pool. This in turn induces DNA damage in tumor cells and inhibits proliferation, suggesting that SIRT5 may serve as a potential anticancer target.
Injections and Infections: Understanding Syringe Service Program Utilization in a Rural State
Authors: Thakarar Kinna , Sankar Nitysari , Murray Kimberly , Lucas Frances Lee , Burris Deb , Smith Robert 
Published: March 2021

Abstract
Background: Increasing rates of injection drug use (IDU) associated-infections suggest significant syringe service program (SSP) underutilization. Our study objective was to assess patient knowledge, attitudes, and practices of safe injection techniques and to determine predictors of SSP utilization in a rural state. Patients and Methods: This was a fifteen-month cross-sectional study of participants hospitalized with IDU-associated infections in Maine. Data were collected through Audio Computer-Assisted Self-Interview survey and medical record review. Descriptive analyses were performed to characterize injection knowledge, attitudes and practices. The primary outcome was SSP utilization, and the main independent variable was self-reported distance to SSP. Logistic regression analyses were performed to identify factors associated SSP utilization, controlling for gender, homelessness, history of overdose, having primary care physician and distance to SSP. Results: Of the 101 study participants, 65 participants (64%) reported past 3 month SSP utilization, though only 33% used SSPs frequently. Many participants (57%) lived more than 10 miles from an SSP. Participants who lived less than 10 miles of an SSP were more likely to use an SSP (adjusted odds ratio 5.39; 95% CI 1.9-15.7). Conclusions Our study highlights unsafe injection practices and lack of frequent SSP utilization among people admitted with IDU-associated infections in a rural state. Especially given increasing stimulant use, these results also highlight the need for SSP access even among individuals prescribed medication for opioid use disorder. Particularly in rural areas where patients may live more than 10 miles from an SSP, expansion of harm reduction services, including mobile units, should be a priority.