Miracle-dz/UniFAR-FTUs huggingface dataset:
13C‐metabolic flux analysis of human adenovirus infection: Implications for viral vector production

Adenoviruses are human pathogens increasingly used as gene therapy and vaccination vectors. However, their impact on cell metabolism is poorly characterized. We performed carbon labeling experiments with [1,2‐13C]glucose or [U‐13C]glutamine to evaluate metabolic alterations in the amniocyte‐derived, E1‐transformed 1G3 cell line during production of a human adenovirus type 5 vector (AdV5). Nonstationary 13C‐metabolic flux analysis revealed increased fluxes of glycolysis (17%) and markedly PPP (over fourfold) and cytosolic AcCoA formation (nearly twofold) following infection of growing cells. Interestingly, infection of growth‐arrested cells increased overall carbon flow even more, including glutamine anaplerosis and TCA cycle activity (both over 1.5‐fold), but was unable to stimulate the PPP and was associated with a steep drop in AdV5 replication (almost 80%). Our results underscore the importance of nucleic and fatty acid biosynthesis for adenovirus replication. Overall, we portray a metabolic blueprint of human adenovirus infection, highlighting similarities with other viruses and cancer, and suggest strategies to improve AdV5 production. Biotechnol. Bioeng. 2017;114: 195–207. © 2016 Wiley Periodicals, Inc.
Magnetically controlled Growing Rods for Early-onset Scoliosis: A Multicenter Study of 23 Cases With Minimum 2 years Follow-up

Study Design. Retrospective study. Objective. To report 2-year clinical and radiographic results of patients treated with magnetically controlled growing rods (MCGR). Summary of Background Data. MCGR for early-onset scoliosis has been reported to provide adequate spinal growth and curve correction by eliminating surgical lengthening procedures. This study was designed to report the results of MCGR patients with 2-year follow-up. Methods. A retrospective study of MCGR patients with the following inclusion criteria: (i) major curve size ≥30°, (ii) T1-T12 height <22 cm, (iii) <11-years old; all at the time of index surgery was performed. Of 54 patients enrolled, 23 had 2-year follow-up. Both primary and conversion patients were evaluated at baseline 6, 12, and 24 months. Results. Mean preoperative age in the primary group was 6.6 ± 2.6 years versus 8.3 ± 2.2 years for the conversion group. A total of 41 adverse events occurred in 11 patients, of which 14 events were implant related. Major coronal curve magnitude improved from 61.3° to 34.3° from baseline to postoperation in primary cases and from 49.4° to 43.8° in conversion cases. Curve correction was maintained for 2 years in both groups. T1-S1 height improved from 252.7 to 288.9 mm in primary cases and was maintained for 2 years. However, conversion cases had some decline in T1- S1 height (270.3 at baseline to 294.4 mm post-MCGR and 290.2 mm at 2-year follow-up; mean loss of 4.2 mm (1.5%) from postoperation to 2 years, P > 0.05). Conclusion. This study showed satisfactory curve correction and growth is achieved among primary cases. T1-S1 height in conversion cases had a slight decline in 2 years. However, this decline was not statistically significant. Level of Evidence: 3
CONTEXTUALIZED RECOMMENDATION BASED ON REALITY MINING FROM MOBILE SUBSCRIBERS

It is difficult to be aware of the personal context for providing a mobile recommendation, because each person's activities and preferences are ambiguous and depend upon numerous unknown factors. In order to solve this problem, we have focused on a reality mining to discover social relationships (e.g., family, friends, etc.) between people in the real world. We have assumed that the personal context for any given person is interrelated with those of other people, and we have investigated how to take into account a person's neighbor's contexts, which possibly have an important influence on his or her personal context. This requires that given a dataset, we have to discover the hidden social networks which express the contextual dependencies between people. In this paper, we propose a semiautomatic approach to build meaningful social networks by repeating interactions with human experts. In this research project, we have applied the proposed system to discover the social networks among mobile subscribers. We have collected and analyzed a dataset of approximately two million people.
Stem cells for spinal cord injury: Strategies to inform differentiation and transplantation

The complex pathology of spinal cord injury (SCI), involving a cascade of secondary events and the formation of inhibitory barriers, hampers regeneration across the lesion site and often results in irreversible loss of motor function. The limited regenerative capacity of endogenous cells after SCI has led to a focus on the development of cell therapies that can confer both neuroprotective and neuroregenerative benefits. Stem cells have emerged as a candidate cell source because of their ability to self‐renew and differentiate into a multitude of specialized cell types. While ethical and safety concerns impeded the use of stem cells in the past, advances in isolation and differentiation methods have largely mitigated these issues. A confluence of work in stem cell biology, genetics, and developmental neurobiology has informed the directed differentiation of specific spinal cell types. After transplantation, these stem cell‐derived populations can replace lost cells, provide trophic support, remyelinate surviving axons, and form relay circuits that contribute to functional recovery. Further refinement of stem cell differentiation and transplantation methods, including combinatorial strategies that involve biomaterial scaffolds and drug delivery, is critical as stem cell‐based treatments enter clinical trials. Biotechnol. Bioeng. 2017;114: 245–259. © 2016 Wiley Periodicals, Inc.
Metallosis Presenting as a Progressive Neurologic Deficit Four Years After a Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis: A Case Report

Study Design. A case report. Objective. The aim of this study was to report a case of progressive pain and paraparesis secondary to metallosis four years after a pediatric posterior spinal fusion (PSF). Summary of Background Data. Metallosis as a late complication of pediatric spinal surgery is rarely reported. Myelographic computed tomography (CT) can be helpful in establishing the diagnosis. The use of serum chromium levels as a means of definitive diagnosis has been suggested, but has only been reported retrospectively. Methods. A 19-year-old male presented four years after PSF for adolescent idiopathic scoliosis with sudden onset of pain and neurologic deficits. Radiographs and CT scan suggested infection. Intraoperatively, no purulent material was noted, but black and yellowish corrosive debris was found around the right L1 pedicle screw, so it was removed and the cavity packed with tobramycin impregnated calcium sulfate beads. After surgery, neurologic deficits worsened. CT myelogram showed irregular opacification of the thecal sac at the level of the conus. A posterior laminectomy and decompression was performed with removal of all debris and spinal instrumentation. Metallosis within the spinal canal was noted and serum chromium levels were obtained. Results. The patient was discharged one week after admission with improvement of pain and gradual improvement in neurologic examination. Three years postdischarge, the patient is asymptomatic and examination shows bilateral clonus. Serum chromium levels declined from a high of 4.5 &mgr;g/L operatively to 0.8 at final follow-up (normal: 0.2–0.6 &mgr;g/L). Conclusion. Although uncommon, metallosis should be considered in the differential diagnosis of any late presenting case of pain, infection-like symptoms, or neurologic deficits after pediatric PSF. CT myelography and serum chromium levels may help guide diagnosis; however, surgical exploration is needed for definitive diagnosis and treatment. Level of Evidence: 4
Synthetic gene design—The rationale for codon optimization and implications for molecular pharming in plants

Degeneracy in the genetic code allows multiple codon sequences to encode the same protein. Codon usage bias in genes is the term given to the preferred use of particular synonymous codons. Synonymous codon substitutions had been regarded as “silent” as the primary structure of the protein was not affected; however, it is now accepted that synonymous substitutions can have a significant effect on heterologous protein expression. Codon optimization, the process of altering codons within the gene sequence to improve recombinant protein expression, has become widely practised. Multiple inter‐linked factors affecting protein expression need to be taken into consideration when optimizing a gene sequence. Over the years, various computer programmes have been developed to aid in the gene sequence optimization process. However, as the rulebook for altering codon usage to affect protein expression is still not completely understood, it is difficult to predict which strategy, if any, will design the “optimal” gene sequence. In this review, codon usage bias and factors affecting codon selection will be discussed and the evidence for codon optimization impact will be reviewed for recombinant protein expression using plants as a case study. These developments will be relevant to all recombinant expression systems; however, molecular pharming in plants is an area which has consistently encountered difficulties with low levels of recombinant protein expression, and should benefit from an evidence based rational approach to synthetic gene design. Biotechnol. Bioeng. 2017;114: 492–502. © 2016 Wiley Periodicals, Inc.
Comparison of Outcomes of Single-Level Anterior Cervical Discectomy With Fusion and Single-Level Artificial Cervical Disc Replacement for Single-Level Cervical Degenerative Disc Disease

Study Design. A single-center, prospective comparative study of prospectively collected outcomes, with a minimum 12 months follow-up. Objectives. The primary purpose of the study is to investigate the clinical, functional, and radiological outcomes of cervical total disc replacement (CTDR) in comparison with anterior cervical discectomy and fusion (ACDF) in the treatment of single-level cervical disc degenerative disease, prospectively. Summary of Background Data. CTDR has recently been an alternative to ACDF in cervical disc degenerative disease to preserve the motion at the treated level. Methods. This study included 34 patients, who underwent either single-level ACDF (n = 17) or single-level CTDR (n = 17) at C3 to C7 level for cervical disc degenerative disease between July 2012 to April 2014 with a minimum of 12 months of follow-up. Results. Neck disability index, visual analog scale, and neck-arm pain score showed significant difference between the two groups at final follow-up of 12 months. Modified orthopedic association score and Nurick scale also showed the Japanese significant difference between the two groups at final follow-up of 12 months. Odom criteria were not statistically significant between the two groups at final follow-up. The changes in overall cervical sagittal angle (CSA) were significantly different between the two groups. The segmental angle (SA) was maintained at a significantly higher value in the CTDR group than in the ACDF group during the follow-up period (P < 0.05). The range of motion of the cervical spine and the treated level was well maintained and improved in the CTDR group as compared with ACDF group and showed extremely statistically significant difference between the two groups. Conclusion. CTDR was found to be a safe, effective, better, and efficient alternative to the traditional ACDF. CTDR using Prestige LP cervical disc provided a statistically significant clinical, functional, and radiological outcomes between the two groups after 1-year follow-up. Level of Evidence: 2
Identification of key genes involved in polysaccharide bioflocculant synthesis in Bacillus licheniformis

The present study reports the sequenced genome of Bacillus licheniformis CGMCC 2876, which is composed of a 4,284,461 bp chromosome that contains 4,188 protein‐coding genes, 72 tRNA genes, and 21 rRNA genes. Additional analysis revealed an eps gene cluster with 16 open reading frames. Conserved Domains Database analysis combined with qPCR experiments indicated that all genes in this cluster were involved in polysaccharide bioflocculant synthesis. Phosphoglucomutase and UDP‐glucose pyrophosphorylase were supposed to be key enzymes in polysaccharide secretion in B. licheniformis. A biosynthesis pathway for the production of polysaccharide bioflocculant involving the integration of individual genes was proposed based on functional analysis. Overexpression of epsDEF from the eps gene cluster in B. licheniformis CGMCC 2876 increased the flocculating activity of the recombinant strain by 90% compared to the original strain. Similarly, the crude yield of polysaccharide bioflocculant was enhanced by 27.8%. Overexpression of the UDP‐glucose pyrophosphorylase gene not only increased the flocculating activity by 71% but also increased bioflocculant yield by 13.3%. Independent of UDP‐N‐acetyl‐D‐mannosamine dehydrogenase gene, flocculating activity, and polysaccharide yield were negatively impacted by overexpression of the UDP‐N‐acetylglucosamine 2‐epimerase gene. Overall, epsDEF and gtaB2 were identified as key genes for polysaccharide bioflocculant synthesis in B. licheniformis. These results will be useful for further engineering of B. licheniformis for industrial bioflocculant production. Biotechnol. Bioeng. 2017;114: 645–655. © 2016 Wiley Periodicals, Inc.
Use of S2-Alar-iliac Screws Associated With Less Complications Than Iliac Screws in Adult Lumbosacropelvic Fixation

Study Design. Retrospective comparative study. Objective. To compare clinical and radiographic outcomes between the S2-alar-iliac (S2AI) and the iliac screw (IS) techniques in the adult population and clarify the clinical strength of S2AI screws. Summary of Background Data. S2AI screws have been described as an alternative method for lumbosacropelvic fixation in place of ISs. The S2AI technique has several advantages with lower prominence, increased ability to directly connect to proximal instrumentation, less extensive dissection of tissue, and enhanced biomechanical strength over the IS technique. However, the clinical significance of these advantages remains unclear. Methods. A single-center retrospective review of patients who underwent lumbosacropelvic fixation yielded 25 IS group patients and 65 S2AI group patients. Baseline demographic information, postoperative complications, pain and functional outcomes, and screw-related outcomes were collected. Results. The S2AI group had lower rates of reoperation (8.8% vs. 48.0%, P < 0.001), surgical site infection (SSI) (1.5% vs. 44.0%, P < 0.001), wound dehiscence (1.5% vs. 36.0%, P < 0.001), and symptomatic screw prominence (0.0% vs. 12.0%, P = 0.02) than the IS group, whereas rates of L5-S1 pseudarthrosis, proximal junctional failure, and sacroiliac joint pain were similar in both groups. Statistically significant pain relief and functional recovery were achieved in both groups without any significant intergroup differences. On multivariate analyses, age [odds ratio (OR) = 0.91, P = 0.004] and S2AI instrumentation (OR = 0.08, P < 0.001) were protective of reoperation, whereas diabetes mellitus (OR = 10.9, P = 0.03) and preoperative diagnosis of tumor (OR = 12.3, P = 0.04) were associated with SSI, and S2AI instrumentation (OR = 0.09, P < 0.001) was protective of SSI. Conclusion. The use of the S2AI technique over the IS technique was an independent predictor of preventing reoperation and SSI, while achieving similar clinical and functional outcomes. Level of Evidence: 4
Enhancing functional expression of codon‐optimized heterologous enzymes in Escherichia coli BL21(DE3) by selective introduction of synonymous rare codons

Rare codon in a heterologous gene may cause premature termination of protein synthesis, misincorporation of amino acids, and/or slow translation of mRNA, decreasing the heterologous protein expression. However, its hypothetical function pertaining to functional protein folding has been barely reported. Here, we investigated the effects of selective introduction of synonymous rare codons (SRCs) to two codon‐optimized (i.e., rare codon‐free) genes sucrose phosphorylase (SP) gene from Thermoanaerobacterium thermosaccharolyticum and amidohydrolase gene from Streptomyces caatingaensis on their expression levels in Escherichia coli BL21(DE3). We investigated the introduction of a single SRC to the coding regions of alpha‐helix, beta‐strand, or linker in the first half of rare codon‐free sp and ah gene. The introduction of a single SRC in the beginning of the coding regions of beta‐strand greatly enhanced their soluble expression levels as compared to the other regions. Also, we applied directed evolution to test multi‐SRC‐containing sp gene mutants for enhanced soluble SP expression levels. To easily identify the soluble SP expression level of colonies growing on Petri dishes, mCherry fluorescent protein was used as a SP‐folding reporter when it was fused to the 3′ end of the sp gene mutant libraries. After three rounds of screening, the best sp gene mutant containing nine SRCs exhibited an approximately six‐fold enhancement in soluble protein expression level as compared to the wild‐type and rare codon‐free sp control. This study suggests that the selective introduction of SRCs can attenuate translation at specific points and such discontinuous attenuation can temporally separate the translation of segments of the peptide chains and actively coordinates their co‐translational folding, resulting in enhanced functional protein expression. Biotechnol. Bioeng. 2017;114: 1054–1064. © 2016 Wiley Periodicals, Inc.
An Approach for Dynamic Identification of Online Radicalization in Social Networks

The Online Social Network (OSN) has evolved as a popular platform enabling rich topic-centric interactions and serving as a medium to facilitate online radicalization (Behr et al. 2013). Keeping in view the growing need of uncovering online radicalization, we focus on the information network of Twitter and present an approach for identifying dynamic communities, which arise due to “radical” topic-centric user interactions. The approach at successive timestamps deploys evolving topic-entity maps along with evolving interaction graphs. We propose “Rate of Overlap (ROAct)” to determine the similarity among successive community timestamps. We further validate our approach using an open dataset of criminal offences in the city of Denver, Colorado. The approach presented is simple, fast, and effective for dynamic identification of topic-centric communities and, thus, will enable law enforcement agencies to identify hidden radicalization.
Anterior Spinal Overgrowth Is the Result of the Scoliotic Mechanism and Is Located in the Disc

Study Design. Cross-sectional study. Objective. To investigate the presence and magnitude of anterior spinal overgrowth in neuromuscular scoliosis and compare this with the same measurements in idiopathic scoliosis and healthy spines. Summary of Background Data. Anterior spinal overgrowth has been described as a potential driver for the onset and progression of adolescent idiopathic scoliosis (AIS). Whether this anterior overgrowth is specific for AIS or also present in nonidiopathic scoliosis has not been reported. Methods. Supine computed tomography (CT) scans of thirty AIS patients (thoracic Cobb 21–81°), thirty neuromuscular (NM) scoliotic patients (thoracic Cobb 19–101°) and 30 nonscoliotic controls were used. The difference in length in per cents between the anterior and posterior side {[(&Dgr;A-P)/P]*100%, abbreviated to A-P%} of each vertebral body and intervertebral disc, and between the anterior side of the spine and the spinal canal (A-C%) were determined. Results. The A-P% of the thoracic curves did not differ between the AIS (+1.2 ± 2.2%) and NM patients (+0.9 ± 4.1%, P = 0.663), both did differ, however, from the same measurements in controls (–3.0 ± 1.6%; P < 0.001) and correlated linearly with the Cobb angle (AIS r = 0.678, NM r = 0.687). Additional anterior length was caused by anterior elongation of the discs (AIS: A-P% disc +17.5 ± 12.7% vs. A-P% body –2.5 ± 2.6%; P < 0.001, NM: A-P% disc +19.1 ± 18.0% vs. A-P% body –3.5 ± 5.1%; P < 0.001). The A-C% T1-S1 in AIS and NM patients were similar (+7.9 ± 1.8% and +8.7 ± 4.0%, P = 0.273), but differed from the controls (+4.2 ± 3.3%; P < 0.001). Conclusion. So called anterior overgrowth has been postulated as a possible cause for idiopathic scoliosis, but apparently it occurs in scoliosis with a known origin as well. This suggests that it is part of a more generalized scoliotic mechanism, rather than its cause. The fact that the intervertebral discs contribute more to this increased anterior length than the vertebral bodies suggests an adaptation to altered loading, rather than a primary growth disturbance. Level of Evidence: 4
Best Practices for Outpatient Anterior Cervical Surgery: Results From a Delphi Panel

Study Design. Delphi Panel expert panel consensus and narrative literature review. Objective. To obtain expert consensus on best practices for patient selection and perioperative decision making for outpatient anterior cervical surgery (anterior cervical disc fusion (ACDF) and cervical total disc replacement (CTDR)). Summary of Background Data. Spine surgery in ambulatory settings is becoming a preferred option for both patients and providers. The transition from traditional inpatient environments has been enabled by innovation in anesthesia protocols and surgical technique, as well as favorable economics. Studies have demonstrated that anterior cervical surgery (ACDF and CTDR) can be performed safely on an outpatient basis. However, practice guidelines and evidence-based protocols to inform best practices for the safe and efficient performance of these procedures in same-day, ambulatory settings are lacking. Methods. A panel of five neurosurgeons, three anesthesiologists, one orthopedic spine surgeon, and a registered nurse was convened to comprise a multidisciplinary expert panel. A three-round modified-Delphi method was used to generate best-practice statements. Predetermined consensus was set at 70% for each best-practice statement. Results. A total of 94 consensus statements were reviewed by the panel. After three rounds of review, there was consensus for 83 best-practice statements, while 11 statements failed to achieve consensus. All statements within several perioperative categories (and subcategories) achieved consensus, including preoperative assessment (n = 8), home-care/follow-up (n = 2), second-stage recovery (n = 18), provider economics (n = 8), patient education (n = 14), discharge criteria (n = 4), and hypothermia prevention (n = 6). Conclusion. This study obtained expert-panel consensus on best practices for patient selection and perioperative decision making for outpatient anterior cervical surgery (ACDF/CTDR). Given a paucity of guidelines and a lack of established care pathways for ACDF/CTDR in same-day, ambulatory settings, results from this study can supplement available evidence in support of local protocol development for providers considering a transition to the outpatient environment. Level of Evidence: 4