bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reversing 21 years of chronic paralysis via non‐invasive spinal cord neuromodulation: a case study
Authors: Alam Monzurul , Ling Yan To , Wong Arnold Y. L. , Zhong Hui , Edgerton Victor Reggie , Zheng Yong‐Ping 
Published: May 2020

AbstractObjectiveThe objective of the current study was to investigate if a non‐invasive spinal cord neuromodulation modality could restore sensorimotor functions in a patient with chronic spinal cord injury (SCI).MethodsIn this study, transcutaneous electrical stimulation (tES) to the spinal cord was utilized to restore sensorimotor functions in a chronic SCI patient who sustained a traumatic C7 cervical cord injury 21 years ago. At baseline, the patient had very limited volitional movement in her right leg, and her left leg was completely paralyzed. tES parameters were optimized in eight stimulation sessions before the treatment. The therapeutic stimulation involved biphasic tES, applied to T11 and L1 spinal levels during a 1‐hour standing and walking training, 2–4 times per week for 16 weeks.ResultsOur pre‐treatment tests indicated that a shorter burst duration (100 µsec) was more effective than a longer burst duration of tES in improving functional movements. After 32 training sessions with tES, the patient regained significant left‐leg volitional movements (grade 0 to grade 10 according to the ISNCSCI scale). Right‐leg motor scores also increased from 17 to 21. The tES treatment also improved her pinprick sensation (from 73 to 79). Upon completion of the treatment (52 sessions), the patient’s standing ability noticeably improved. She could stabilize her knee to stand without any assistance. She could also squat while holding onto a walker.InterpretationThese promising results demonstrate beneficial effects of non‐invasive tES in regaining volitional control of plegic lower limbs in patients with chronic paralysis.
Al(OTf)3‐Catalyzed Tandem Coupling Reaction between N,N‐Disubstituted Aminomalonitriles and Substituted Arenes: a Synthesis of 1‐Cyano‐bisindolylmethane Analogues≠
Authors: Lei Lin‐Sheng , Wang Bo‐Wen , Jin Da‐Ping , Gao Zhu‐Peng , Huan‐Liang  , Wang Shao‐Hua , Xu Xue‐Tao , Zhang Kun , Zhang Xiao‐Yun 
Published: May 2020

AbstractA synthesis of 1‐cyano‐bisindolylmethane analogues via an Al(OTf)3‐catalyzed tandem coupling reaction between N,N‐disubstituted aminomalonitriles and substituted arenes has been developed. This method not only provides an alternative synthetic strategy for the synthesis of corresponding functional molecules, but also enriches the volume of bisarylmethanes library to facilitate related functional studies.magnified image
Planting date, cultivar, seed treatment, and seeding rate effects on soybean growth and yield
Authors: Nleya Thandiwe , Schutte Matthew , Clay David , Reicks Graig , Mueller Nathan 
Published: May 2020

AbstractSoybean [Glycine max (L.) Merr.] yield is a function of many factors including genetic attributes of the cultivar, environmental conditions, and management practices. Temporally variable weather patterns in North America, especially in the northern Great Plains, have resulted in the re‐examination of how spring production practices interact with the environmental conditions to influence yield. This study evaluated the impact of four plantings dates, four seeding rates, and two soybean maturity groups (MGs) using treated and untreated (control) seed on soybean growth, seed yield, and composition. The study was conducted at Volga, SD, in 2014, 2015, and 2016. The planting dates in the study ranged from early May to early July and the four seeding rates were 247,000; 333,500; 420,000; 506,500 seeds ha−1. Stand establishment decreased as seeding rate increased irrespective of planting date. The number of growing degree days (GDDs) to R1 decreased with delayed planting. Delayed planting also decreased the number of GDDs to R8, the length of the reproductive phase (R1−R8), and seed yield. Delayed planting decreased seed yield for both MGs but the rate of decrease was greater for MG 2.4 than MG 1.4. Seed treatment increased seed yield irrespective of planting date. Seed protein was variable among planting dates and between MGs while seed oil decreased with delayed planting. The research documents the impact of delayed planting on soybean yield and quality and highlights the importance of early planting in soybean irrespective of maturity group and growth habit.
Long‐term survival outcomes following laparoscopic surgery for clinical stage 0/I rectal carcinoma
Authors: Ito Masaaki , Yamamoto Seiichiro , Okuda Junji , Fujii Shoichi , Yamaguchi Shigeki , Otsuka Koki , Yoshimura Kenichi , Watanabe Masahiko ,   for the Japan Society of Laparoscopic Colorectal Surgery
Published: May 2020

AbstractAimTo clarify and evaluate the long‐term outcomes of laparoscopic surgery for clinical stage 0/I rectal carcinoma patients.MethodsThis single‐arm phase II trial involved accredited surgeons from 43 Japanese institutions. Patients were registered preoperatively. The planned sample size was 490. The primary endpoint was overall survival, and long‐term outcomes were evaluated.ResultsA total of 495 patients were registered between February 2008 and August 2010. Eight patients (1.6%) required conversion to open surgery. Sphincter‐preserving procedures were performed in 477 (97%) patients. Positive radial resection margin was found in two (0.4%) patients. Of 490 patients, 22, 314, 38, 115, and one patient had final pathological stages (p‐stage) 0, I, II, III, and IV, respectively. Pathologically, 31.4% (154/490) of the patients did not have p‐stage 0/I. The 5‐year overall survival (OS) rates in p‐stages 0, I, II, and III were 100%, 98%, 97%, and 94%, respectively. The 5‐year OS of all patients at 96.6% (95% CI 94.6‐97.9) was significantly better than the expected 5‐year OS of 81.1% (P < .0001). The 5‐year relapse‐free survival in p‐stages 0, I, II, and III were 100%, 93%, 81%, and 79%, respectively. The 5‐year relapse‐free survival of all patients was 90.1%. Fifty patients (10.2%) had recurrence; lung recurrence was found in 22 patients, local recurrence in 14, liver in seven, distant lymph node in nine, and bone in three.ConclusionsLaparoscopic surgery for clinical stage 0/I rectal carcinoma has feasible long‐term outcomes. (ClinicalTrials.gov No.NCT00635466.)
Real‐world effectiveness of eliglustat in treatment‐naïve and switch patients enrolled in the International Collaborative Gaucher Group Gaucher Registry
Authors: Mistry Pramod K. , Balwani Manisha , Charrow Joel , Kishnani Priya , Niederau Claus , Underhill Lisa H. , McClain Monica R. 
Published: May 2020

AbstractEliglustat is a first‐line oral therapy for adults with Gaucher disease type 1 (GD1) with extensive, intermediate, or poor CYP2D6‐metabolizer phenotypes (90% of patients). We report real‐world outcomes after 2 years of eliglustat therapy in the International Collaborative Gaucher Group Gaucher Registry (NCT00358943). As of January 2019, baseline and 2‐year data (±1 year) were available for 231 eliglustat‐treated GD1 patients: 19 treatment‐naïve (zero splenectomized) and 212 ERT patients who switched to eliglustat (36 splenectomized). Most patients (89%) were from the United States, where eliglustat was first approved. In treatment‐naïve patients, mean hemoglobin increased from 12.4 to 13.4 g/dL (P = .004, n = 18), mean platelet count increased from 113 to 156 × 109/L (P < .001, n = 17); mean spleen volume decreased from 7.4 to 3.5 multiples of normal (MN) (P = .02, n = 7); mean liver volume remained normal (n = 7), and median spine Z‐score was unchanged (−1.3 to −1.2, n = 6). In non‐splenectomized switch patients, mean hemoglobin remained stable/non‐anemic (n = 167); mean platelet count remained stable/normal (n = 165); mean spleen volume decreased from 3.3 to 2.8 MN (P < .001, n = 64); mean liver volume remained normal (n = 63), and median lumbar spine Z‐score improved from −0.7 to −0.4 (P = .014, n = 68). In splenectomized switch patients, mean hemoglobin remained stable/non‐anemic (n = 31); mean platelet count increased from 297 to 324 × 109/L (non‐significant, n = 29); mean liver volume remained normal (n = 13); median spine Z‐score improved from −0.8 to −0.6 (non‐significant, n = 11). Median chitotriosidase decreased in all groups (P < .01 for all). These real‐world results are consistent with eliglustat clinical trial results demonstrating long‐term benefit in treatment‐naïve patients and stability in ERT switch patients.
Nissen fundoplication in Cornelia de Lange syndrome spectrum: Who are the potential candidates?
Authors: Parma Barbara , Cianci Paola , Mariani Milena , Cereda Anna , Panceri Roberto , Fossati Chiara , Maestri Luciano , Macchini Francesco , Onesimo Roberta , Zampino Giuseppe , Betalli Pietro , Cheli Maurizio , Selicorni Angelo 
Published: May 2020

AbstractCornelia de Lange spectrum (CdLSp) is a rare genetic condition characterized by intellectual disability, facial dysmorphisms, major malformations, growth impairment, and development delay. Approximately 80% of CdLSp patients have gastroesophageal reflux disease (GERD) with a varied clinical presentation. The aim of this study is to define potential clinical/genetic risk factors based on the clinical phenotype description of CdLSp patients with severe GERD who underwent surgical treatment. We retrospectively collected data from 23 CdLSp patients, 13 females and 10 males. Mean age of the patients undergoing surgical treatment was of 4 years. 21/23 (91%) had a molecular characterization, of which 21/21 (100%) had a NIPBL gene mutation, while 2/23 (9%) did not have a genetical characterization, only a clinical diagnosis. Most of our patients presented a moderate–severe severity score (21/23, 91%) with limb malformations evidenced in 10/23 (44%) of our patients and a moderate–severe intellectual disability in 20/23 (87%). Therefore, CdLSp patients harboring NIPBL variants, upper limb malformations and severe psychomotor delay are more likely to suffer from severe GERD, not responsive to proton pump inhibitors treatment. These features should be considered as clinical markers for potentially severe GERD that might require surgical treatment.
Protein and mRNA Delivery Enabled by Cholesteryl‐Based Biodegradable Lipidoid Nanoparticles
Authors: Li Yamin , Jarvis Rachel , Zhu Kuixin , Glass Zachary , Ogurlu Roza , Gao Peiyang , Li Peixuan , Chen Jinjin , Yu Yingjie , Yang Yongjie , Xu Qiaobing 
Published: May 2020

AbstractDeveloping safe and efficient delivery systems for therapeutic biomacromolecules is a long‐standing challenge. Herein, we report a newly developed combinatorial library of cholesteryl‐based disulfide bond‐containing biodegradable cationic lipidoid nanoparticles. We have identified a subset of this library which is effective for protein and mRNA delivery in vitro and in vivo. These lipidoids showed comparable transfection efficacies but much lower cytotoxicities compared to the Lpf2k in vitro. In vivo studies in adult mice demonstrated the successful delivery of genome engineering protein and mRNA molecules in the skeletal muscle (via intramuscular injection), lung and spleen (via intravenous injection), and brain (via lateral ventricle infusion).
Biomolecular Densely Grafted Brush Polymers: Oligonucleotides, Oligosaccharides and Oligopeptides
Authors: Choi Wonmin , Sun Hao , Battistella Claudia , Berger Or , Vratsanos Maria A. , Wang Max M. , Gianneschi Nathan C. 
Published: May 2020

AbstractIn this Minireview, we describe synthetic polymers densely functionalized with sequence‐defined biomolecular sidechains. We focus on synthetic brush polymers of oligonucleotides, oligosaccharides, and oligopeptides, prepared via graft‐through polymerization from biomolecule functionalized monomers. The resulting structures are brush polymers wherein a biomolecular graft is positioned at each monomer backbone unit. We describe key synthetic milestones, identify synthetic opportunities, and highlight recent advances in the field, including biological applications.
Enantioselective Preparation of Arenes with β‐Stereogenic Centers: Confronting the 1,1‐Disubstituted Olefin Problem Using CuH/Pd Cooperative Catalysis
Authors: Lu Zhaohong , Buchwald Stephen L. 
Published: May 2020

AbstractArenes with β‐stereogenic centers are important substructures in pharmaceuticals and natural products. We have developed an asymmetric anti‐Markovnikov hydroarylation of 1,1‐disubstituted olefins by dual palladium and copper hydride catalysis as a convenient and general approach to access these substructures. This efficient one‐step process addresses several limitations of the traditional stepwise approaches. The use of cesium benzoate as a base and a common phosphine ligand for both the Cu‐ and Pd‐catalyzed processes were important discoveries that allow these challenging olefin substrates to be efficiently transformed. A variety of aryl bromide coupling partners, including numerous heterocycles, were coupled with 1,1‐disubstituted alkenes to generate arenes with β‐stereogenic centers.
Synthesis, spectroscopic, electrochemical characterization, density functional theory (DFT), time dependent density functional theory (TD‐DFT), and antibacterial studies of some Co(II), Ni(II), and Cu(II) chelates of (E)‐4‐(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)‐1‐(3‐hydroxynaphthalen‐2‐yl)methylene) thiosemicarbazide Schiff base ligand
Authors: El‐Sawaf Ayman K. , Abdel‐Monem Yasser K. , Azzam Maged A. 
Published: May 2020

AbstractIn this study, mononuclear Co(II), Ni(II), and Cu(II) chelates of the potentially tridentate O, N, S donor ligand (E)‐4‐(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)‐1‐(3‐hydroxynaphthalen‐2‐yl)methylene) thiosemicarbazide (H2L) were synthesized and characterized by elemental analyses, conductivity measurements, Fourier transform infrared spectroscopy, UV–visible spectroscopy, magnetic susceptibility, electron spin resonance (ESR) spectral analysis, thermal thermogravimetric analyses, cyclic voltammetry, and theoretical density functional theory (DFT) and time dependent density functional theory (TD‐DFT) studies. The potential donors O (phenolic) and N (azomethine) are found in asynconfiguration due to a strong intramolecular hydrogen bond [O–H …. N(1)] as shown in the1H NMR spectrum of the free ligand. In addition, analytical results revealed the formation of the metal chelates in a ligand‐to‐metal molar ratio of 1:1. The organic ligand (H2L) coordinated to the metal center through azomethine nitrogen, phenolate oxygen, and thione/thiolate sulfur groups with the formation of a five‐ and six‐membered rings. The magnetic and spectral results supported the formation of tetrahedral geometry around the Co(II) and Ni(II) centers, while Cu(II) centers were assumed to have a square planar geometry. The time dependent density functional theory (TD‐DFT) calculation outputs were used to expect and explain the experimental bathochromic and hypsochromic shifts resulting from the ligand chelation. The antibacterial activity of the compounds under study was evaluatedin vitroagainstStaphylococcus aureusandEscherichia colidemonstrating Gram‐positive and Gram‐negative bacteria, respectively. It was found that among synthesized compounds, Cu(II) chelate5showed the most inhibitory activity against both Gram‐positive and Gram‐negative bacteria when compared to the organic ligand as well as to the other prepared chelates.
Message framing strategies for effective marine conservation communication
Authors: Kolandai‐Matchett Komathi , Armoudian Maria 
Published: May 2020

Abstract

Human activities are a major source of threat to marine ecosystems. Solutions thus require changes to or cessation of those activities in addition to multiple restorative and conservation efforts – all of which, in turn, require public support for success. However, scientific understanding of threats to marine ecosystems has not paralleled public understanding of those threats in many jurisdictions. Highly complex, interwoven, distant, vulnerable to multiple stressors, and hosting biota that are biologically unfamiliar to people, marine ecosystems present unique communication challenges.

The merits of effective communication capable of motivating behavioural change, policy action and support for marine conservation are often emphasized. To date, however, environmental communication, as a field, has largely focused on terrestrial ecosystems and more recently on climate change, leaving research‐informed marine conservation communication neglected.

Adding to the small compilation of marine conservation communication literature, this integrative review provides a new understanding of how six message frames (emotional, problem/solution, outcome, value‐based, distance, and social norm) can interactively help enhance the effectuality of conservation messages. Insights from the framing‐related literature are merged with those from relevant fields including the theoretical literature, and the behavioural, social, and environmental sciences to define concepts, provide examples and explain the relevance of the six identified frames. The potential strength of these frames are discussed and suggestions on how they might be used to communicate different marine conservation issues are provided.
Impacts on product quality attributes of monoclonal antibodies produced in CHO cell bioreactor cultures during intentional mycoplasma contamination events
Authors: Fratz‐Berilla Erica J. , Angart Phillip , Graham Ryan J. , Powers David N. , Mohammad Adil , Kohnhorst Casey , Faison Talia , Velugula‐Yellela Sai Rashmika , Trunfio Nicholas , Agarabi Cyrus 
Published: May 2020

AbstractA mycoplasma contamination event in a biomanufacturing facility can result in costly cleanups and potential drug shortages. Mycoplasma may survive in mammalian cell cultures with only subtle changes to the culture and penetrate the standard 0.2‐µm filters used in the clarification of harvested cell culture fluid. Previously, we reported a study regarding the ability ofMycoplasma argininito persist in a single‐use, perfusion rocking bioreactor system containing a Chinese hamster ovary (CHO) DG44 cell line expressing a model monoclonal immunoglobulin G 1 (IgG1) antibody. Our previous work showed thatM. argininiaffects CHO cell growth profile, viability, nutrient consumption, oxygen use, and waste production at varying timepoints afterM. argininiintroduction to the culture. Careful evaluation of certain identified process parameters over time may be used to indicate mycoplasma contamination in CHO cell cultures in a bioreactor before detection from a traditional method. In this report, we studied the changes in the IgG1 product quality produced by CHO cells considered to be induced by theM. argininicontamination events. We observed changes in critical quality attributes correlated with the duration of contamination, including increased acidic charge variants and high mannose species, which were further modeled using principal component analysis to explore the relationships amongM. argininicontamination, CHO cell growth and metabolites, and IgG1 product quality attributes. Finally, partial least square models using NIR spectral data were used to establish predictions of high levels (≥104colony‐forming unit [CFU/ml]) ofM. argininicontamination, but prediction of levels below 104CFU/ml were not reliable. Contamination of CHO cells withM. argininiresulted in significant reduction of antibody product quality, highlighting the importance of rapid microbiological testing and mycoplasma testing during particularly long upstream bioprocesses to ensure product safety and quality.
Overexpression of the mitochondrial pyruvate carrier reduces lactate production and increases recombinant protein productivity in CHO cells
Authors: Bulté Dubhe B. , Palomares Laura A. , Parra Carolina Gómez , Martínez Juan Andrés , Contreras Martha A. , Noriega Lilia G. , Ramírez Octavio T. 
Published: May 2020

AbstractChinese hamster ovary (CHO) cells are characterized by a low glucose catabolic efficiency, resulting in undesirable lactate production. Here, it is hypothesized that such low efficiency is determined by the transport of pyruvate into the mitochondria. The mitochondrial pyruvate carrier (MPC), responsible for introducing pyruvate into the mitochondria, is formed by two subunits, MPC1 and MPC2. Stable CHO cell lines, overexpressing the genes of both subunits, were constructed to facilitate the entry of pyruvate into the mitochondria and its incorporation into oxidative pathways. Significant overexpression of both genes, compared to the basal level of the control cells, was verified, and subcellular localization of both subunits in the mitochondria was confirmed. Kinetic evaluation of the best MPC overexpressing CHO cells showed a reduction of up to 50% in the overall yield of lactate production with respect to the control. An increase in specific growth rate and maximum viable cell concentration, as well as an increase of up to 40% on the maximum concentration of two recombinant model proteins transiently expressed (alkaline phosphatase or a monoclonal antibody), was also observed. Hybrid cybernetic modeling, that considered 89 reactions, 25 extracellular metabolites, and a network of 62 intracellular metabolites, explained that the best MPC overexpression case resulted in an increased metabolic flux across the mitochondrial membrane, activated a more balanced growth, and reduced the Warburg effect without compromising glucose consumption rate and maximum cell concentration. Overall, this study showed that transport of pyruvate into the mitochondria limits the efficiency of glucose oxidation, which can be overcome by a cell engineering approach.
Asymmetrical cortical vessel sign predicts prognosis after acute ischemic stroke
Authors: Liu Yong‐Lin , Xiao Wei‐Min , Lu Jie‐Kai , Wang Ya‐Zhi , Lu Zhi‐Hao , Zhong Huo‐Hua , Qu Jian‐Feng , Fang Xue‐Wen , Liang Man‐Qiu , Chen Yang‐Kun 
Published: May 2020

AbstractIntroductionTo assess whether the asymmetrical cortical vessel sign (ACVS) on susceptibility‐weighted imaging (SWI) could predict 90‐day poor outcomes in anterior circulation acute ischemic stroke (AIS) patients treated with recombinant tissue plasminogen activator (r‐tPA).MethodsClinical data of consecutive patients with anterior circulation AIS treated with r‐tPA were retrospectively analyzed. Clinical variables included age, sex, vascular risk factors, NIHSS score, onset to treatment time, and initial hematologic and neuroimaging findings. Follow‐up was performed 90 days after onset. Poor outcome was defined as a modified Rankin scale (mRS) ≥3 at 90 days.ResultsA total of 145 patients were included, 35 (24.1%) patients presented with ACVS (≥Grade 1) on SWI. Fifty‐three (36.6%) patients had a poor outcome at 90 days. ACVS (≥Grade 1) occurred in 21 (39.6%) patients with poor outcome compared with 14 (15.2%) patients with favorable outcome (p = .001). Univariate analysis indicated that age, NIHSS score on admission, previous stroke, hemorrhagic transformation, severe intracranial large artery stenosis or occlusion (SILASO), and ACVS were associated with 90‐day poor outcome (p < .05). Since SILASO and ACVS were highly correlated and ACVS had different grades, we used three logistic regression models. Results from the three models showed that ACVS was associated with 90‐day poor outcome.ConclusionsIn r‐tPA‐treated patients with anterior circulation AIS, ACVS might be a helpful neuroimaging predictor for poor outcome at 90 days.