bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ponatinib dose-ranging study in chronic-phase chronic myeloid leukemia: a randomized, open-label phase 2 clinical trial
Authors: Cortes Jorge , Apperley Jane , Lomaia Elza , Moiraghi Beatriz , Undurraga Sutton Maria , Pavlovsky Carolina , Chuah Charles , Sacha Tomasz , Lipton Jeffrey H. , Schiffer Charles A. , McCloskey James , Hochhaus Andreas , Rousselot Philippe , Rosti Gianantonio , de Lavallade Hugues , Turkina Anna , Rojas Christine , Arthur Christopher Kevin , Maness Lori , Talpaz Moshe , Mauro Michael , Hall Tracey , Lu Vickie , Srivastava Shouryadeep , Deininger Michael 
Published: August 2021

Abstract
In PACE (Ponatinib Ph+ ALL and CML Evaluation), a phase 2 trial of ponatinib that included patients with chronic-phase chronic myeloid leukemia (CP-CML) resistant to multiple prior tyrosine kinase inhibitors (TKIs), ponatinib showed deep and durable responses, but arterial occlusive events (AOEs) emerged as notable adverse events. Post hoc analyses indicated that AOEs are dose dependent. We assessed the benefit/risk ratio across 3 ponatinib starting doses in the first prospective study to evaluate a novel, response-based, dose-reduction strategy for TKI treatment. Adults with CP-CML resistant to or intolerant of at least 2 prior BCR-ABL1 TKIs or with a BCR-ABL1 T315I mutation were randomly assigned 1:1:1 to 3 cohorts receiving ponatinib 45, 30, or 15 mg once daily. In patients who received 45 or 30 mg daily the dose was reduced to 15 mg upon response (BCR-ABL1IS transcript levels ≤1%). The primary end point was response at 12 months. From August 2015 through May 2019, 283 patients were randomly assigned to the cohorts: 282 (94 per dose group) received treatment (data cutoff, 31 May 2020). The primary end point (98.3% confidence interval) was achieved in 44.1% (31.7-57.0) in the 45-mg cohort, 29.0% (18.4-41.6) in the 30-mg cohort, and 23.1% (13.4-35.3) in the 15-mg cohort. Independently confirmed grade 3 or above treatment-emergent AOEs occurred in 5, 5, and 3 patients in the 45-, 30-, and 15-mg cohorts, respectively. All cohorts showed benefit in this highly resistant CP-CML population. Optimal benefit/risk outcomes occurred with the 45-mg starting dose, which was decreased to 15 mg upon achievement of a response. This trial is registered on www.clinicaltrials.gov as NCT02467270.
Will whole-genome sequencing become the first-line genetic analysis for male infertility in the near future?
Authors: Ghieh Farah , Barbotin Anne-Laure , Leroy Clara , Marcelli François , Swierkowsky-Blanchard Nelly , Serazin Valérie , Mandon-Pepin Béatrice , Vialard François 
Published: August 2021

AbstractWhereas the initially strategy for the genetic analysis of male infertility was based on a candidate gene approach, the development of next-generation sequencing technologies (such as whole-exome sequencing (WES)) provides an opportunity to analyze many genes in a single procedure. In order to recommend WES or whole-genome sequencing (WGS) after genetic counselling, an objective evaluation of the current genetic screening strategy for male infertility is required, even if, at present, we have to take into consideration the complexity of such a procedure, not discussed in this commentary.
First core microsatellite panel identification in Apennine brown bears (Ursus arctos marsicanus): a collaborative approach
Authors: Scarpulla Erminia , Boattini Alessio , Cozzo Mario , Giangregorio Patrizia , Ciucci Paolo , Mucci Nadia , Randi Ettore , Davoli Francesca 
Published: August 2021

AbstractBackgroundThe low cost and rapidity of microsatellite analysis have led to the development of several markers for many species. Because in non-invasive genetics it is recommended to genotype individuals using few loci, generally a subset of markers is selected. The choice of different marker panels by different research groups studying the same population can cause problems and bias in data analysis. A priority issue in conservation genetics is the comparability of data produced by different labs with different methods. Here, we compared data from previous and ongoing studies to identify a panel of microsatellite loci efficient for the long-term monitoring of Apennine brown bears (Ursus arctos marsicanus), aiming at reducing genotyping uncertainty and allowing reliable individual identifications overtimes.ResultsWe examined all microsatellite markers used up to now and identified 19 candidate loci. We evaluated the efficacy of 13 of the most commonly used loci analyzing 194 DNA samples belonging to 113 distinct bears selected from the Italian national biobank. We compared data from 4 different marker subsets on the basis of genotyping errors, allelic patterns, observed and expected heterozygosity, discriminatory powers, number of mismatching pairs, and probability of identity. The optimal marker set was selected evaluating the low molecular weight, the high discriminatory power, and the low occurrence of genotyping errors of each primer. We calibrated allele calls and verified matches among genotypes obtained in previous studies using the complete set of 13 STRs (Short Tandem Repeats), analyzing six invasive DNA samples from distinct individuals. Differences in allele-sizing between labs were consistent, showing a substantial overlap of the individual genotyping.ConclusionsThe proposed marker set comprises 11Ursusspecific markers with the addition of cxx20, the canid-locus less prone to genotyping errors, in order to prevent underestimation (maximizing the discriminatory power) and overestimation (minimizing the genotyping errors) of the number of Apennine brown bears. The selected markers allow saving time and costs with the amplification in multiplex of all loci thanks to the same annealing temperature. Our work optimizes the available resources by identifying a shared panel and a uniform methodology capable of improving comparisons between past and future studies.
Construction and preservation of a stable and highly expressed recombinant Helicobacter pylori vacuolating cytotoxin A with apoptotic activity
Authors: Yuan Ling-Zhi , Shi Xiao , Tang Dan , Zheng Shao-Peng , Xiao Zhi-Ming , Wang Fen 
Published: August 2021

Abstract
Background
H. pylori is closely related to the occurrence and development of various digestive gastritis, peptic ulcer and mucosa-associated lymphoid tissue (MALT) lymphoma. H. pylori is also a class I carcinogen of gastric cancer. VacA is the only exocrine toxin of H. pylori, which plays a very important role in the pathogenesis of H. pylori. The production of VacA in natural circumstances is complex with heavy workload and low yield. Therefore, it is very important to obtain recombinant VacA protein which is stable and biologically active. This study therefore aims to explore the expression, purification and stable storage of VacA toxin of H. pylori in E.coli, and to provide experimental basis for further exploration of the role of VacA in H. pylori -induced inflammation of cancer.

Results
A 2502-bp fragment and VacA gene were identified. An 89.7-kDa VacA34–854 recombinant protein was expressed and purified from the recombinant engineering bacteria and was preserved stably in 50 mM acetic acid buffer (pH 2.9). The amount of the recombinant protein was larger in the inclusion bodies than in the supernatant. In addition, after a 24-h culture with VacA recombinant protein, GES-1 cells demonstrated evidence of apoptosis including early nuclear immobilization and clustering under inverted microscope and TEM. It was found that VacA recombinant protein induced apoptosis by TUNEL assay.

Conclusions
A VacA recombinant protein that is stably and highly expressed and possesses pro-apoptotic activity is successfully constructed. The protein is stably preserved in 50 mM acetic acid buffer (pH 2.9).
Comprehensive genomic survey, structural classification and expression analysis of C2H2-type zinc finger factor in wheat (Triticum aestivum L.)
Authors: Li Yongliang , Sun Aolong , Wu Qun , Zou Xiaoxiao , Chen Fenglin , Cai Ruqiong , Xie Hai , Zhang Meng , Guo Xinhong 
Published: August 2021

Abstract
Background
The C2H2-type zinc finger proteins (C2H2-ZFPs) are one of major classes of transcription factors that play important roles in plant growth, development and stress responses. Limit information about the C2H2-ZF genes hinders the molecular breeding in bread wheat (Triticum aestivum).

Results
In this study, 457 C2H2-ZFP proteins (including 253 splice variants), which contain four types of conserved domain (named Q, M, Z, and D), could be further classified into ten subsets. They were identified to be distributed in 21 chromosomes in T. aestivum. Subset-specific motifs, like NPL-, SFP1-, DL- (EAR-like-motif), R-, PL-, L- and EK-, might make C2H2-ZFP diverse multifunction. Interestingly, NPL- and SFP1-box were firstly found to be located in C2H2-ZFP proteins. Synteny analyses showed that only 4 pairs of C2H2 family genes in T. aestivum, 65 genes in B. distachyon, 66 genes in A. tauschii, 68 genes in rice, 9 genes in Arabidopsis, were syntenic relationships respectively. It indicated that TaZFPs were closely related to genes in Poaceae. From the published transcriptome data, totally 198 of 204 TaC2H2-ZF genes have expression data. Among them, 25 TaC2H2-ZF genes were certificated to be significantly differentially expressed in 5 different organs and 15 different development stages by quantitative RT-PCR. The 18 TaC2H2-ZF genes were verified in response to heat, drought, and heat & drought stresses. According to expression pattern analysis, several TaZFPs, like Traes_5BL_D53A846BE.1, were not only highly expressed in L2DAAs, RTLS, RMS, but also endowed tolerance to drought and heat stresses, making them good candidates for molecular breeding.

Conclusions
This study systematically characterized the TaC2H2-ZFPs and their potential roles in T. aestivum. Our findings provide new insights into the C2H2-ZF genes in T. aestivum as well as a foundation for further studies on the roles of TaC2H2-ZF genes in T. aestivum molecular breeding.
Drought stress introduces growth, physiological traits and ecological stoichiometry changes in two contrasting Cunninghamia lanceolata cultivars planted in continuous-plantation soils
Authors: Bian Fangyuan , Wang Yukui , Duan Baoli , Wu Zhizhuang , Zhang Yuanbing , Bi Yufang , Wang Anke , Zhong Hao , Du Xuhua 
Published: August 2021

Abstract
Background
The decrease in Cunninghamia lanceolata (Lamb.) production on continuously planted soil is an essential problem. In this study, two-year-old seedlings of two cultivars (a normal cultivar, NC, and a super cultivar, SC) were grown in two types of soil (not planted (NP) soil; continuously planted (CP) soil) with three watering regimes, and the interactive effects on plant growth and physiological traits were investigated in a greenhouse experiment. The water contents of the soil in the control (CK) (normal water content), medium water content (MWC) and low water content (LWC) treatments reached 75−80 %, 45−50 % and 20−25 % of the field water capacity, respectively.

Results
The results indicated that the CP soil had a negative effect on growth and physiological traits and that the LWC treatment caused even more severe and comprehensive negative effects. In both cultivars, the CP soil significantly decreased the height increment (HI), basal diameter increment (DI), dry matter accumulation (DMA), net photosynthetic rate (Pn), total chlorophyll content (TChl), carotenoid content (Caro) and photosynthetic nitrogen use efficiency (PNUE). Compared to the NP soil, the CP soil also decreased the proline and soluble protein contents, nitrogen use efficiency (NUE) and phosphorus use efficiency (PUE) and increased the nitrogen:phosphorus ratio in roots, stems and leaves. The LWC treatment decreased growth and photosynthesis, changed ecological stoichiometry, induced oxidative stress, promoted water use efficiency and damaged chloroplast ultrastructure. Significant increases in ascorbate peroxidase (APX), peroxidase (POD), soluble protein and proline contents were found in the LWC treatment. Compared with the NC, the SC was more tolerant to the CP soil and water stress, as indicated by the higher levels of DMA, Pn, and WUE. After exposure to the CP soil and watering regimes, the decreases in biomass accumulation and gas exchange were more pronounced.

Conclusions
The combination of drought and CP soil may have detrimental effects on C. lanceolata growth, and low water content enhances the impacts of CP soil stress on C. lanceolata seedlings. The superiority of the SC over the NC is significant in Chinese fir plantation soil. Therefore, continuously planted soil can be utilized to cultivate improved varieties of C. lanceolata and maintain water capacity. This can improve their growth and physiological performance to a certain extent.
Electrocardiographic and electrophysiological characteristics of idiopathic ventricular arrhythmias with acute successful ablation at the superior portion of the mitral annulus
Authors: Di Chengye , Letsas Konstantinos P. , Gao Peng , Wang Qun , Wu Yanxi , Lin Wenhua 
Published: August 2021

AbstractBackgroundWe sought to identify the electrocardiographic and electrophysiological characteristics of ventricular arrhythmias (VAs), including idiopathic ventricular tachycardia (VT) and premature ventricular contractions (PVCs), with acute successful radiofrequency catheter ablation (RFCA) at the superior portion of the mitral annulus (SP-MA).Methods and resultsAmong 437 consecutive patients who presented with VAs for RFCA, twenty-six patients with acute successful RFCA at the SP-MA were included in this study. The ratio of the amplitude of the first positive peak (if present) versus the nadir in the unipolar electrogram (EGM) was 0.00–0.03 (0.00) at the acute successful RFCA site. The time interval between the QRS onset and the maximum descending slope (D-Max) in the unipolar EGM (QRS-Uni) was 18.8 ± 13.6 ms. With bipolar mapping, the ventricular QRS (V-QRS) interval was 3.75–17.3 (11) ms, 6 (23.1%) patients showed the earliest V-QRS interval of 0 ms, and the other 20 patients (76.9%) showed a V-QRS interval of 10–54 ms. The RFCA start-to-effect time was 14.1 ± 7.2 s in 23 patients (88.5%). In the remaining 3 patients (11.5%), the mean duration of successful RFCA was not well defined due to the infrequent nature of clinical VAs during RFCA. Early (within 3 days) and late (1-year) recurrence rates were 23.1% (6 patients) and 26.9% (7 patients), respectively. VAs disappeared 3 days later due to delayed RFCA efficacy in 2 patients (7.7%). No complications occurred during the RFCA procedure or the one-year follow-up.ConclusionsSP-MA VAs are a rare but distinct subgroup of VAs. Bipolar and unipolar EGM features can help to determine the optimal RFCA site, and the QRS-Uni interval may serve as a marker that could be used to guide RFCA.
The therapeutic effects of excimer laser coronary atherectomy therapy for in-stent restenosis chronic total occlusions
Authors: Li Hui , Ai Hu , Li Le , Zheng Naixin , Tang Guodong , Yang Guojian , Zhao Ying , Sun Fucheng , Zhang Huiping 
Published: August 2021

Abstract
Objectives
To evaluate the safety and efficacy of excimer laser coronary atherectomy (ELCA) in patients with in-stent restenosis chronic total occlusions (ISR CTOs).

Background
ISR CTOs are a challenge in percutaneous coronary intervention (PCI). Although they can be treated by ELCA, limited data are available on the effects of ELCA treatment in these patients.

Methods
Fifty-nine consecutive patients underwent PCI for ISR CTOs at Beijing Hospital between December 2017 and September 2020. According to whether or not ELCA was performed, they were divided into two groups. Quantitative coronary angiography (QCA) analyses were performed routinely, including measurement of the minimal lumen diameter and calculation of the percentage diameter stenosis. The procedural success rate, the frequency of peri-procedural complications, and the incidence rates of major adverse cardiac events (MACEs) over nine months were assessed. The primary endpoint in the study was the percentage diameter stenosis.

Results
Procedure success was achieved in most patients in both groups (75.9%). Patients in the ELCA group exhibited a lower percentage diameter stenosis (24.5 ± 9.09 vs. 35.1 ± 18.6, p = 0.048) and a larger minimal lumen diameter (2.36 ± 0.29 mm vs. 1.78 ± 0.64 mm, p < 0.001) than those in the control group and the 9-month incidence rates of MACEs did not differ (9.5% vs 15.8%, p = 0.699).

Conclusions
This study demonstrated that ELCA may be a safe and effective technique in the treatment of ISR CTOs, and the use of ELCA can achieve good immediate angiographic results, as measured by QCA, without increasing peri-procedural complications or the incidence rates of 9-month MACEs.
Serum albumin levels as a predictive biomarker for low-load resistance training programs’ effects on muscle thickness in the community-dwelling elderly Japanese population: interventional study result
Authors: Sawada Shuji , Ozaki Hayao , Natsume Toshiharu , Nakano Daiki , Deng Pengyu , Yoshihara Toshinori , Osawa Takuya , Kobayashi Hiroyuki , Machida Shuichi , Naito Hisashi 
Published: August 2021

AbstractBackgroundResistance training has been recommended as an effective measure against age-related loss of muscle mass and muscle strength, called sarcopenia, even in older adults. However, despite subjecting each participant to the same training program, the training effect solely depended on the individual. This study aimed to evaluate whether certain blood parameters influenced the effect of a low-load resistance training program on muscle thickness in the community-dwelling elderly population.MethodsSixty-nine community-dwelling Japanese (49 women and 20 men) subjects aged 69.4 ± 6.5 years were included. Low-load resistance training was performed twice a week for 12 weeks. Muscle thickness at the anterior aspects of the thigh (AT) was measured using a B-mode ultrasound device, and 22 blood parameter levels were assessed before and after the program. We checked the first quartile value of each parameter to establish cutoff values, and participants were divided into low or normal groups for each parameter.ResultsA low-load resistance training program significantly increased muscle thickness at the AT. The interaction between time and groups was examined at low (< 4.1 g/dL) versus normal (≥ 4.1 g/dL) serum albumin (Alb) levels. Although there was no difference in muscle thickness at the AT before the training intervention, the hypertrophic effects were higher in the normal serum Alb level group than in the low serum Alb level group. The binomial logistic regression analysis showed that participants in the low serum Alb group had an odds ratio of 7.08 for decreased muscle thickness at the AT. The effect of a low-load resistance training program on lower limb muscle thickness appears to be limited in participants with low serum Alb levels before training interventions.ConclusionsSerum Alb level may act as a biomarker to predict the effects of low-load resistance training programs on muscle hypertrophy in elderly individuals.Trial registrationThis study was retrospectively registered in UMIN-Clinical Trial Registry (CTR), ID:UMIN000042759(date of registration, 14 Dec 2020).
Mononucleosis-like illnesses due to co-infection with severe fever with thrombocytopenia syndrome virus and spotted fever group rickettsia:a case report
Authors: Zhao Bin , Hou Haohua , Gao Ran , Tian Bing , Deng Baocheng 
Published: August 2021

Abstract
Background
We report a mononucleosis-like illnesses case due to co-infection with severe fever with thrombocytopenia syndrome virus (SFTSV) and spotted fever group rickettsia (SFGR), which to the best of our knowledge, has never been reported .

Case presentation
A 64-year-old male with an 11-day history of fever, sore throat, malaise, nausea, and non-pruritic rash was admitted to our emergency department. Prior to admission, he was bitten by ticks. Laboratory tests revealed a white blood cell count of 24,460 cells/μL with 25% atypical lymphocytes and 20% mononucleosis, thrombocytopenia. Test results were positive for SFTSV RNA, SFTSV-specific IgM antibody, and SFGR-specific IgM antibody. He was diagnosed with mononucleosis-like illnesses due to co-infection with SFTSV and SFGR. After administration of doxycycline, he recovered completely.

Conclusions
The clinical presentation may be atypical in co-infection with SFTSV and SFGR. This finding highlighted the importance of considering SFGR infection, as well as a SFSTV and SFGR co-infection for the differential diagnosis of patients bitten by ticks in SFTSV-endemic areas.
Guillain-Barré syndrome as the first presentation of human immunodeficiency virus infection
Authors: Lopes Mariana , Marques Patrícia , Silva Bruno , Cruz Gonçalo , Serra José Eduardo , Ferreira Eugenia , Alves Helena , da Cunha José Saraiva 
Published: August 2021

Abstract
Aim
Antiretroviral therapy (ART) development has reduced the severity of neurological complications of the human immunodeficiency virus (HIV), but they remain prevalent and need prompt recognition. Acute inflammatory demyelinating polyneuropathy (AIDP) is a rare complication of human immunodeficiency virus (HIV) infection that may appear at any stage of the disease. In this case, AIDP represents a late presentation of HIV infection.

Methods
Descriptive study. Patient data were collected from their medical records and by health assessment interviews.

Results
We report a case of a 52-year-old male with acute lower limb weakness. Given the suggestive clinical presentation of AIDP and a positive HIV test, intravenous immunoglobulin (IVIG) was administered along with antiretroviral therapy. Progressive weakness to the upper limbs, autonomic dysfunction, and pain was observed. The second regimen of IVIG plus corticosteroids was administered. Muscle strength improved after three weeks.

Conclusions
Screening for HIV in a patient with AIDP may provide a better outcome because of the early start of ART with good central nervous system penetration in HIV-infected patients.