bluuebunny/crossref_metadata_2025_split huggingface dataset:
High HIV-1 Virological Failure and Drug Resistance among Adult Patients Receiving First-Line ART for At least 12 Months at a Decentralized Urban HIV Clinic Setting in Senegal before the Test-and-Treat
Authors: Ekollo Mbange Aristid , Malick Diouara Abou Abdallah , Diop-Ndiaye Halimatou , Diaw Diouf Ndèye Aminata , Ngom-Ngueye Ndèye Fatou , Ndiaye Touré Kine , Dieng Ahmed , Lô Seynabou , Fall Mamadou , Fon Mbacham Wilfred , Mboup Souleymane , Touré-Kane Coumba 
Published: May 2021

Background: The feasibility of antiretroviral therapy (ART) monitoring remains problematic in decentralized HIV clinic settings of sub-Saharan Africa. We assessed the rates and correlates of HIV-1 virological failure (VF) and drug resistance (DR) in 2 pre-test-and-treat urban clinic settings of Senegal. Methods: Consenting HIV-1-infected adults (⩾18 years) receiving first-line ART for ⩾12 months were cross-sectionally enrolled between January and March 2015, at the referral outpatient treatment center of Dakar (n = 151) and decentralized regional hospital of Saint-Louis (n = 127). In the 12 months preceding plasma specimens’ collection patients at Saint-Louis had no viral load (VL) testing. Significant predictors of VF (VL ⩾ 1000 copies/ml) and DR (clinically relevant mutations) were determined using binomial logistic regression in R software. Results: Of the 278 adults on EFV-/NVP-based regimens, 32 (11.5% [95%CI: 8.0-15.9]) experienced VF. Failing and non-failing patients had comparable median time [interquartile] on ART (69.5 [23.0-89.5] vs 64.0 [34.0-99.0] months; P = .46, Mann–Whitney U-test). Of the 27 viraemic isolates successfully genotyped, 20 (74.1%) carried DR mutations; most frequent were M184VI (55.6%), K103N (37.1%), thymidine analog mutations (29.6%), Y181CY (22.2%). The pattern of mutations did not always correspond to the ongoing treatment. The adjusted odds of VF was significantly associated with the decentralized clinic site ( P < .001) and CD4 < 350 cells/mm3 ( P < .006). Strong correlates of DR also included Saint-Louis ( P < .009), CD4 < 350 cells/mm3 ( P <. 001), and nevirapine-based therapies (comparator: efavirenz-based therapies; P < .027). In stratification analyses by site, higher rate of VF at Saint-Louis (20.5% [95%CI: 13.8-28.5] vs 4.0% [95%CI: 1.5-8.5] in Dakar) was associated with nevirapine-based therapies (OR = 3.34 [1.07-11.75], P = .038), self-reported missing doses (OR = 3.30 [1.13-10.24], P = .029), and medical appointments (OR = 2.91 [1.05-8.47], P = .039) in the last 1 and 12 months(s), respectively. The higher rate of DR at Saint-Louis (12.9% [95%CI: 7.6-20.1] vs 2.7% [95%CI: 0.7-6.7] in Dakar) was associated with nevirapine-based therapies (OR = 5.13 [1.12-37.35], P = .035). Conclusion: At decentralized urban settings, there is need for enhanced virological monitoring and adherence support. HIV programs in Senegal should intensify early HIV diagnosis for effective test-and-treat. These interventions, in addition to the superiority of efavirenz-based therapies provide a favorable framework for transitioning to the recommended potent drug dolutegravir, thereby ensuring its long-term use.
Identification of clinical phenotypes in schizophrenia: the role of lurasidone
Authors: Riva Marco Andrea , Albert Umberto , de Filippis Sergio , Vita Antonio , De Berardis Domenico 
Published: May 2021

The treatment of schizophrenia includes the control of symptoms, the prevention of relapses, and amelioration of adaptive skills for patient re-integration into society. Antipsychotic drugs are the agents of choice for the treatment of schizophrenia, as they reduce the positive symptoms of psychosis. Lurasidone is a second-generation antipsychotic drug representing a novel and useful clinical tool for the management of schizophrenia. A board consisting of a panel of Italian expert psychiatrists was organized with the following aims: (a) defining the current modalities of use of lurasidone, highlighted through 17 specific questions; (b) defining and agreeing the main features of the drug and the principal reasons to suggest its administration. We established that lurasidone is suggested at any age, with no gender difference, at all stages of the disease. The switch from previous treatments is done primarily because of lack of efficacy as well as poor adherence/tolerability. Lurasidone is among the best-tolerated antipsychotics, and its use is indicated in the presence of different comorbidities. A wide range of dosages is available, allowing safe titration in particular cases, with the highest dose (148 mg) generally used for the treatment of the acute phase. The discontinuation rate due to poor tolerability, low compliance, and interactions with other drugs is very low. Akathisia is the most reported adverse event, but it may be controlled by dose reduction. Lurasidone does not possess a marked sedative action but, in agitated patients, can be associated with sedative drugs, such as benzodiazepines. The most frequent reason for switching to other therapies is the need for long-acting formulations, as in patients at risk of very low adherence or suicide. Lurasidone does not strongly impact metabolism or the cardiovascular system (QT interval), and does not influence the metabolism of other drugs, showing good efficacy and tolerability.
The Value of Three-Dimensional Printing Spine Model in Severe Spine Deformity Correction Surgery
Authors: Pan Aixing , Ding Hongtao , Hai Yong , Liu Yuzeng , Hai Junrui Jonathan , Yin Peng , Han Bo 
Published: May 2021

Study Design: Retrospective case-control study. Objective: We aimed to evaluate the value of 3-dimensional printing (3DP) spine model in the surgical treatment of severe spinal deformity since the prosperous development of 3DP technology. Methods: Severe scoliosis or hyper-kyphosis patients underwent posterior fixation and fusion surgery using the 3DP spine models were reviewed (3DP group). Spinal deformity surgeries operated by free-hand screw implantation during the same period were selected as the control group after propensity score matching (PSM). The correction rate, pedicle screw accuracy, and complications were analyzed. Class A and B screws were defined as accurate according to Gertzbein and Robbins criteria. Results: 35 patients were enrolled in the 3DP group and 35 matched cases were included in the control group. The perioperative baseline data and deformity correction rate were similar between both groups ( P > .05). However, the operation time and blood loss were significantly less in the 3DP group (296.14 ± 66.18 min vs. 329.43 ± 67.16 min, 711.43 ± 552.28 mL vs. 1322.29 ± 828.23 mL, P < .05). More three-column osteotomies (Grade 3-6) were performed in the 3DP group (30/35, 85.7% vs. 21/35, 60.0%. P = .016). The screw placement accuracy was significantly higher in the 3DP group (422/582, 72.51% vs. 397/575, 69.04%. P = .024). The screw misplacement related complication rate was significantly higher in the free-hand group (6/35 vs. 1/35, P = .046). Conclusions: The study provided solid evidence that 3DP spine models can enhance surgeons’ confidence in performing higher grade osteotomies and improve the safety and efficiency in severe spine deformity correction surgery. 3D printing technology has a good prospect in spinal deformity surgery.
GlcNAc is a mast-cell chromatin-remodeling oncometabolite that promotes systemic mastocytosis aggressiveness
Authors: Agopian Julie , Da Costa Quentin , Nguyen Quang Vo , Scorrano Giulia , Kousteridou Paraskevi , Yuan Min , Chelbi Rabie , Goubard Armelle , Castellano Remy , Maurizio Julien , Teodosio Cristina , De Sepulveda Paulo , Asara John M. , Orfao Alberto , Hermine Olivier , Dubreuil Patrice , Brenet Fabienne 
Published: May 2021

AbstractSystemic mastocytosis (SM) is a KIT-driven hematopoietic neoplasm characterized by the excessive accumulation of neoplastic mast cells (MCs) in various organs and, mainly, the bone marrow (BM). Multiple genetic and epigenetic mechanisms contribute to the onset and severity of SM. However, little is known to date about the metabolic underpinnings underlying SM aggressiveness, which has thus far impeded the development of strategies to leverage metabolic dependencies when existing KIT-targeted treatments fail. Here, we show that plasma metabolomic profiles were able to discriminate indolent from advanced forms of the disease. We identified N-acetyl-d-glucosamine (GlcNAc) as the most predictive metabolite of SM severity. High plasma levels of GlcNAc in patients with advanced SM correlated with the activation of the GlcNAc-fed hexosamine biosynthesis pathway in patients BM aspirates and purified BM MCs. At the functional level, GlcNAc enhanced human neoplastic MCs proliferation and promoted rapid health deterioration in a humanized mouse model of SM. In addition, in the presence of GlcNAc, immunoglobulin E-stimulated MCs triggered enhanced release of proinflammatory cytokines and a stronger acute response in a mouse model of passive cutaneous anaphylaxis. Mechanistically, elevated GlcNAc levels promoted the transcriptional accessibility of chromatin regions that contain genes encoding mediators of receptor tyrosine kinases cascades and inflammatory responses, thus leading to a more aggressive phenotype. Therefore, GlcNAc is an oncometabolite driver of SM aggressiveness. This study suggests the therapeutic potential for targeting metabolic pathways in MC-related diseases to manipulate MCs effector functions.
Long-term outcomes after gene therapy for adenosine deaminase severe combined immune deficiency
Authors: Reinhardt Bryanna , Habib Omar , Shaw Kit L. , Garabedian Elizabeth , Carbonaro-Sarracino Denise A. , Terrazas Dayna , Fernandez Beatriz Campo , De Oliveira Satiro , Moore Theodore B. , Ikeda Alan K. , Engel Barbara C. , Podsakoff Gregory M. , Hollis Roger P. , Fernandes Augustine , Jackson Connie , Shupien Sally , Mishra Suparna , Davila Alejandra , Mottahedeh Jack , Vitomirov Andrej , Meng Wenzhao , Rosenfeld Aaron M. , Roche Aoife M. , Hokama Pascha , Reddy Shantan , Everett John , Wang Xiaoyan , Luning Prak Eline T. , Cornetta Kenneth , Hershfield Michael S. , Sokolic Robert , De Ravin Suk See , Malech Harry L. , Bushman Frederic D. , Candotti Fabio , Kohn Donald B. 
Published: May 2021

Abstract
Patients lacking functional adenosine deaminase activity have severe combined immunodeficiency (ADA SCID), which can be treated with ADA enzyme replacement therapy (ERT), allogeneic hematopoietic stem cell transplantation (HSCT), or autologous HSCT with gene-corrected cells (gene therapy [GT]). A cohort of 10 ADA SCID patients, aged 3 months to 15 years, underwent GT in a phase 2 clinical trial between 2009 and 2012. Autologous bone marrow CD34+ cells were transduced ex vivo with the MND (myeloproliferative sarcoma virus, negative control region deleted, dl587rev primer binding site)–ADA gammaretroviral vector (gRV) and infused following busulfan reduced-intensity conditioning. These patients were monitored in a long-term follow-up protocol over 8 to 11 years. Nine of 10 patients have sufficient immune reconstitution to protect against serious infections and have not needed to resume ERT or proceed to secondary allogeneic HSCT. ERT was restarted 6 months after GT in the oldest patient who had no evidence of benefit from GT. Four of 9 evaluable patients with the highest gene marking and B-cell numbers remain off immunoglobulin replacement therapy and responded to vaccines. There were broad ranges of responses in normalization of ADA enzyme activity and adenine metabolites in blood cells and levels of cellular and humoral immune reconstitution. Outcomes were generally better in younger patients and those receiving higher doses of gene-marked CD34+ cells. No patient experienced a leukoproliferative event after GT, despite persisting prominent clones with vector integrations adjacent to proto-oncogenes. These long-term findings demonstrate enduring efficacy of GT for ADA SCID but also highlight risks of genotoxicity with gRVs. This trial was registered at www.clinicaltrials.gov as #NCT00794508.
Chassis Coordinated Control for Full X-by-Wire Vehicles-A Review
Authors: Zhang Lei , Zhang Zhiqiang , Wang Zhenpo , Deng Junjun , Dorrell David G. 
Published: May 2021

AbstractAn X-by-wire chassis can improve the kinematic characteristics of human-vehicle closed-loop system and thus active safety especially under emergency scenarios via enabling chassis coordinated control. This paper aims to provide a complete and systematic survey on chassis coordinated control methods for full X-by-wire vehicles, with the primary goal of summarizing recent reserch advancements and stimulating innovative thoughts. Driving condition identification including driver's operation intention, critical vehicle states and road adhesion condition and integrated control of X-by-wire chassis subsystems constitute the main framework of a chassis coordinated control scheme. Under steering and braking maneuvers, different driving condition identification methods are described in this paper. These are the trigger conditions and the basis for the implementation of chassis coordinated control. For the vehicles equipped with steering-by-wire, braking-by-wire and/or wire-controlled-suspension systems, state-of-the-art chassis coordinated control methods are reviewed including the coordination of any two or three chassis subsystems. Finally, the development trends are discussed.
Studying Formability Limits By Combining Conventional and Incremental Sheet Forming Process
Authors: Lora Fabio Andre , Fritzen Daniel , Alves de Sousa Ricardo , Schaffer Lirio 
Published: May 2021

AbstractIn this work it is assessed the potential of combining conventional and incremental sheet forming processes in a same sheet of metal. This so-called hybrid forming approach is performed through the manufacture of a pre-forming by conventional forming, followed by incremental sheet forming. The main objective is analyzing strain evolution. The pre-forming induced in the conventional forming stage will determine the strain paths, directly influencing the strains produced by the incremental process. To conduct the study, in the conventional processes, strains were imposed in three different ways with distinct true strains. At the incremental stage, the pyramid strategy was adopted with different wall slopes. From the experiments, the true strains and the final geometries were analyzed. Numerical simulation was also employed for the sake of comparison and correlation with the measured data. It could be observed that single-stretch pre-strain was directly proportional to the maximum incremental strains achieved, whereas samples subjected to biaxial pre-strain influenced the formability according to the degree of pre-strain applied. Pre-strain driven by the prior deep-drawing operation did not result, in this particular geometry, in increased formability.
The Interaction between Rice Genotype and Magnaporthe oryzae Regulates the Assembly of Rice Root-Associated Microbiota
Authors: Tian Dagang , Chen Zaijie , Lin Yan , Liang Tingmin , Chen Ziqiang , Guo Xinrui , Wang Feng , Wang Zonghua 
Published: May 2021

Abstract
Background
Utilizating the plant microbiome to enhance pathogen resistance in crop production is an emerging alternative to the use of chemical pesticides. However, the diversity and structure of the microbiota, and the assembly mechanisms of root-associated microbial communities of plants are still poorly understood.

Results
We invstigated the microbiota of the root endosphere and rhizosphere soils of the rice cultivar Nipponbare (NPB) and its Piz-t-transgenic line (NPB-Piz-t) when infected with the filamentous fungus Magnaporthe oryzae (M. oryzae) isolate KJ201, using 16S rRNA and internal transcribed spacer 1 (ITS1) amplicon sequencing. The rhizosphere soils showed higher bacterial and fungal richness and diversity than the endosphere except for fungal richness in the rhizosphere soils of the mock treatment. Bacteria richness and diversity increased in the endospheric communities of NPB and Piz-t under inoculation with KJ201 (referred to as ‘NPB-KJ201’ and ‘Piz-t-KJ201’, respectively) compared with the corresponding mock treatments, with the NPB-KJ201 showing the highest diversity in the four bacterial endocompartments. In contrast, fungal richness and diversity decreased in the endospheric communities of NPB-KJ201 and Piz-t-KJ201, relative to the corresponding mock treatments, with NPB-KJ201 and Piz-t-KJ201 having the lowest richness and diversity, respectively, across the four fungal endocompartments. Principal component analysis (PCA) indicated that the microbiota of Piz-t-KJ201 of root endophytes were mostly remarkablely distinct from that of NPB-KJ201. Co-occurrence network analysis revealed that the phyla Proteobacteria and Ascomycota were the key contributors to the bacterial and fungal communities, respectively. Furthermore, a comparative metabolic analysis showed that the contents of tryptophan metabolism and indole alkaloid biosynthesis were significantly lower in the Piz-t-KJ201 plants.

Conclusions
In this study, we compared the diversity, composition, and assembly of microbial communities associated with the rhizosphere soils and endosphere of Piz-t-KJ201 and NPB-KJ201. On the basis of the different compositions, diversities, and assemblies of the microbial communities among different compartments, we propose that the host genotype and inoculation pattern of M. oryzae played dominant roles in determining the microbial community assemblage. Further metabolomics analysis revealed that some metabolites may influence changes in bacterial communities. This study improves our understanding of the complex interactions between rice and M. oryzae, which could be useful in developing new strategies to improve rice resistance through the manipulation of soil microorganisms.
Combining genetic algorithm with machine learning strategies for designing potent antimicrobial peptides
Authors: Boone Kyle , Wisdom Cate , Camarda Kyle , Spencer Paulette , Tamerler Candan 
Published: May 2021

AbstractBackgroundCurrent methods in machine learning provide approaches for solving challenging, multiple constraint design problems. While deep learning and related neural networking methods have state-of-the-art performance, their vulnerability in decision making processes leading to irrational outcomes is a major concern for their implementation. With the rising antibiotic resistance, antimicrobial peptides (AMPs) have increasingly gained attention as novel therapeutic agents. This challenging design problem requires peptides which meet the multiple constraints of limiting drug-resistance in bacteria, preventing secondary infections from imbalanced microbial flora, and avoiding immune system suppression. AMPs offer a promising, bioinspired design space to targeting antimicrobial activity, but their versatility also requires the curated selection from a combinatorial sequence space. This space is too large for brute-force methods or currently known rational design approaches outside of machine learning. While there has been progress in using the design space to more effectively target AMP activity, a widely applicable approach has been elusive. The lack of transparency in machine learning has limited the advancement of scientific knowledge of how AMPs are related among each other, and the lack of general applicability for fully rational approaches has limited a broader understanding of the design space.MethodsHere we combined an evolutionary method with rough set theory, a transparent machine learning approach, for designing antimicrobial peptides (AMPs). Our method achieves the customization of AMPs using supervised learning boundaries. Our system employs in vitro bacterial assays to measure fitness, codon-representation of peptides to gain flexibility of sequence selection in DNA-space with a genetic algorithm and machine learning to further accelerate the process.ResultsWe use supervised machine learning and a genetic algorithm to find a peptide active againstS. epidermidis, a common bacterial strain for implant infections, with an improved aggregation propensity average for an improved ease of synthesis.ConclusionsOur results demonstrate that AMP design can be customized to maintain activity and simplify production. To our knowledge, this is the first time when codon-based genetic algorithms combined with rough set theory methods is used for computational search on peptide sequences.
A detailed map of coupled circadian clock and cell cycle with qualitative dynamics validation
Authors: Rougny Adrien , Paulevé Loïc , Teboul Michèle , Delaunay Franck 
Published: May 2021

Abstract
Background
The temporal coordination of biological processes by the circadian clock is an important mechanism, and its disruption has negative health outcomes, including cancer. Experimental and theoretical evidence suggests that the oscillators driving the circadian clock and the cell cycle are coupled through phase locking.

Results
We present a detailed and documented map of known mechanisms related to the regulation of the circadian clock, and its coupling with an existing cell cycle map which includes main interactions of the mammalian cell cycle. The coherence of the merged map has been validated with a qualitative dynamics analysis. We verified that the coupled circadian clock and cell cycle maps reproduce the observed sequence of phase markers. Moreover, we predicted mutations that contribute to regulating checkpoints of the two oscillators.

Conclusions
Our approach underlined the potential key role of the core clock protein NR1D1 in regulating cell cycle progression. We predicted that its activity influences negatively the progression of the cell cycle from phase G2 to M. This is consistent with the earlier experimental finding that pharmacological activation of NR1D1 inhibits tumour cell proliferation and shows that our approach can identify biologically relevant species in the context of large and complex networks.