bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance milestones in postoperative physical therapy after total hip arthroplasty: impact on length of stay and discharge destination
Authors: Vaudreuil Nicholas J. , McGlaston Timothy J. , Gulledge Catarina D. , Bove Allyn M. , Klatt Brian A. 
Published: May 2018

Background:
Early postoperative physical therapy (PT) regimens after total hip arthroplasty (THA) have become the standard of care at most institutions. Initiating PT on postoperative day (POD) 0 after THA has been shown to shorten hospital length of stay (LOS). However, objective performance milestones for early therapy are not well established.

Methods:
This study retrospectively reviewed 277 patients who underwent primary THA. Specific data assessed included demographic information, number of feet walked at the POD 0 and POD 1 PT evaluations, LOS, and discharge destination. The primary outcome assessed was the relationship between performance in PT with both LOS and discharge destination. For those patients who could not participate in therapy, reasons cited by therapy documentation were recorded.

Results:
Patients who received POD 0 PT had a shorter LOS (P=0.032), decreased discharge to extended care facility (ECF) (P<0.001), and walked farther in PT on POD 1 (P<0.001). Ambulating farther than 10 feet on POD 0 or 100 feet on POD 1 resulted in significant decreases in LOS (P=0.005, P<0.001) and in the percentage of patients discharged to an ECF (P=0.027, P<0.001). The most common reason for inability to participate in therapy was late arrival to the inpatient floor.

Conclusions:
Achieving mobility milestones is a key factor in the determination of a patient’s discharge timing and destination after THA. Limited data exist validating objective performance milestones for patients receiving early PT after THA. This study suggests that achieving mobility milestones on POD 0 and 1 can significantly improve short-term outcomes.
The hidden cost of training orthopaedic surgery residents to perform an open carpal tunnel release
Authors: Daley Dane N. , Patterson Travis M. , Peterson Ann M. , Kokko Kyle P. 
Published: May 2018

Background:
Training orthopaedic surgery residents is time consuming and expensive. The objective of the current study was to determine the time and costs associated with teaching orthopaedic residents to perform an open carpal tunnel release (CTR).

Methods:
A retrospective chart review of a single orthopaedic hand surgeon’s outpatient surgical cases over 18 mo was performed. One hundred-six isolated open carpal tunnel releases were identified. Seventy-seven were performed while training orthopaedic surgery residents, and 29 were performed by the attending surgeon alone. Standard demographics, post-graduate year (PGY) of training, and surgical times were abstracted from the charts.

Results:
The time (minutes) required to perform a CTR for PGY-2, 3, and 4 when compared to the attending surgeon was 13.8±3.5 (P=0.012), 16.4±4.9 (P<0.001) and 13.1±4.2 (P=0.044), respectively, with a resident average of 13.7±4.2 min. The attending surgeon required 10.4±4.2 min, which is 3.3 min less than the average resident time (P<0.001). There was no statistically significant difference when comparing surgical times between resident years of training.

Conclusions:
Orthopaedic surgical residents on average required 32% more surgical time to perform an open CTR. Total ambulatory operating room and anesthesia charge was approximately $137/min at our institution with a collection rate of 27% resulting in a per minute cost equal to $37/min. The 77 cases performed while training residents added an additional $34,811.70 in charges with a resultant $9,401.70 in reimbursement.

Level of Evidence:
Level IV, retrospective review.
Time Course of Radiologic Changes After Lumbar Total Disc Replacement
Authors: Hur Jung-Woo , Kim Jin-Sung , Ryu Kyeong-Sik , Shin Myeong-Hoon , Park Chun-Kun 
Published: May 2018

Study Design:
This was a retrospective observatory analysis study.

Objective:
The purpose of this study was to evaluate long-term safety and therapeutic effectiveness of the lumbar total disc replacement (TDR) using ProDisc-L by analyzing the radiologic changes at the index and adjacent levels in minimum 5-year follow-up.

Summary of Background Data:
Early successful clinical results of lumbar TDR have been reported. However, few reports have published its therapeutic effectiveness and radiologic degenerative changes at the index and adjacent segments in the long term.

Materials and Methods:
Forty-three patients were followed-up for at least 60 months. Radiologic changes were assessed by segmental range of motion (ROM) at the index and adjacent levels, global lumbar lordosis, and disc space height (DSH). The magnetic resonance imaging and computed tomographic scans were used to determine the facet arthrosis and intervertebral disc degeneration at the index and adjacent levels.

Results:
Gradual decrements of DSH restoration were observed until the last follow-up. Mean global and segmental ROM of index segments were significantly reduced (P=0.044, 0.00) at the last visit. There were 21 patients (48.8%) with no motion at index segment (ROM<0.5 degrees) at the last visit. Among the 56 segments operated on, progression of facet arthrosis was observed in 30.3% of index segments and 10.9% of adjacent segments. None of the postoperative radiologic parameters included in the present study presented significant correlation with clinical outcome.

Conclusions:
The study demonstrates that only half of the lumbar TDR patients can maintain segmental motion at the index level >5-year after surgery and TDR provides a good clinical outcome postoperatively regardless of motion preservation or DSH height preservation at the last follow-up. After TDR, the degenerative changes in the index and adjacent segments advanced as compared with our previous report of 2-year follow-up, however, these changes did not appear to exert negative influence upon clinical outcomes.
Ensemble allosteric model: energetic frustration within the intrinsically disordered glucocorticoid receptor
Authors: White Jordan T. , Li Jing , Grasso Emily , Wrabl James O. , Hilser Vincent J. 
Published: May 2018

Allostery is an important regulatory phenomenon enabling precise control of biological function. Initial understanding of allostery was gained from seminal work on conformational changes exhibited by structured proteins. Within the last decade, protein allostery has also been demonstrated to occur within intrinsically disordered proteins. This emerging concept of disorder-mediated allostery can be usefully understood in the context of a thermodynamic ensemble. The advantage of this ensemble allosteric model is that it unifies the explanations of allostery occurring within both structured and disordered proteins. One central finding from this model is that energetic coupling, the transmission of a signal between separate regions (or domains) of a protein, is maximized when one or more domains are disordered. This is due to a disorder–order transition that contributes additional coupling energy to the allosteric system through formation of a molecular interaction surface or interface. A second key finding is that multiple interfaces may constructively or destructively interfere with each other, resulting in a new form of allosteric regulation called ‘energetic frustration’. Articulating protein allostery in terms of the thermodynamic ensemble permits formulation of experimentally testable hypotheses which can increase fundamental understanding and direct drug-design efforts. These ideas are illustrated here with the specific case of human glucocorticoid receptor, a medically important multi-domain allosteric protein that contains both structured and disordered regions and exemplifies ‘energetic frustration’.
This article is part of a discussion meeting issue ‘Allostery and molecular machines’.
Shared dynamics of LeuT superfamily members and allosteric differentiation by structural irregularities and multimerization
Authors: Ponzoni Luca , Zhang She , Cheng Mary Hongying , Bahar Ivet 
Published: May 2018

The LeuT-fold superfamily includes secondary active transporters from different functional families, which share a common tertiary structure, despite having a remarkably low sequence similarity. By identifying the common structural and dynamical features upon principal component analysis of a comprehensive ensemble of 90 experimentally resolved structures and anisotropic network model evaluation of collective motions, we provide a unified point of view for understanding the reasons why this particular fold has been selected by evolution to accomplish such a broad spectrum of functions. The parallel identification of conserved sequence features, localized at specific sites of transmembrane helices, sheds light on the role of broken helices (TM1 and TM6 in LeuT) in promoting ion/substrate binding and allosteric interconversion between the outward- and inward-facing conformations of transporters. Finally, the determination of the dynamics landscape for the structural ensemble provides a promising framework for the classification of transporters based on their dynamics, and the characterization of the collective movements that favour multimerization.
This article is part of a discussion meeting issue ‘Allostery and molecular machines’.
Markov models for the elucidation of allosteric regulation
Authors: Sengupta Ushnish , Strodel Birgit 
Published: May 2018

Allosteric regulation refers to the process where the effect of binding of a ligand at one site of a protein is transmitted to another, often distant, functional site. In recent years, it has been demonstrated that allosteric mechanisms can be understood by the conformational ensembles of a protein. Molecular dynamics (MD) simulations are often used for the study of protein allostery as they provide an atomistic view of the dynamics of a protein. However, given the wealth of detailed information hidden in MD data, one has to apply a method that allows extraction of the conformational ensembles underlying allosteric regulation from these data. Markov state models are one of the most promising methods for this purpose. We provide a short introduction to the theory of Markov state models and review their application to various examples of protein allostery studied by MD simulations. We also include a discussion of studies where Markov modelling has been employed to analyse experimental data on allosteric regulation. We conclude our review by advertising the wider application of Markov state models to elucidate allosteric mechanisms, especially since in recent years it has become straightforward to construct such models thanks to software programs like PyEMMA and MSMBuilder.
This article is part of a discussion meeting issue ‘Allostery and molecular machines’.
Synthesis of oxyfunctionalized NSAID metabolites by microbial biocatalysts
Authors: Klenk Jan M. , Kontny Lisa , Nebel Bernd A. , Hauer Bernhard 
Published: May 2018

AbstractThe synthesis of valuable metabolites and degradation intermediates of drugs, like non-steroidal anti-inflammatory drugs (NSAIDs), are substantially for toxicological and environmental studies, but efficient synthesis strategies and the metabolite availability are still challenging aspects. To overcome these bottlenecks filamentous fungi as microbial biocatalysts were applied. Different NSAIDs like diclofenac, ibuprofen, naproxen and mefenamic acid could be oxyfunctionalized to produce human metabolites in isolated yields of up to 99% using 1 g L−1 of substrate. Thereby the biotransformations using Beauveria bassiana, Clitocybe nebularis or Mucor hiemalis surpass previous reported chemical, microbial and P450-based routes in terms of efficiency. In addition to different hydroxylated compounds of diclofenac, a novel metabolite, 3’,4’-dihydroxydiclofenac, has been catalyzed by B. bassiana and the responsible P450s were identified by proteome analysis. The applied filamentous fungi present an interesting alternative, microbial biocatalysts platform for the production of valuable oxyfunctionalized drug metabolites.ImportanceThe occurrence of pharmaceutically active compounds, such as diclofenac and its metabolites, in the environment, in particular in aquatic systems, is of increasing concern because of the increased application of drugs. Standards of putative metabolites are therefore necessary for environmental studies. Moreover, pharmaceutical research and development requires assessment of the bioavailability, toxicity and metabolic fate of potential new drugs to ensure its safety for users and the environment. Since most of the reactions in the early pharmacokinetics of drugs are oxyfunctionalizations catalysed by P450s, oxyfunctionalized metabolites are of major interest. However, to assess these metabolites chemical synthesis often suffer from multistep reactions, toxic substances, polluting conditions and achieve only low regioselectivity. Biocatalysis can contribute to this by using microbial cell factories. The significance of our research is to complement or even exceed synthetic methods for the production of oxyfunctionalized drug metabolites.
A constrained SSU-rRNA phylogeny reveals the unsequenced diversity of photosynthetic Cyanobacteria (Oxyphotobacteria)
Authors: Cornet Luc , Wilmotte Annick , Javaux Emmanuelle J. , Baurain Denis 
Published: May 2018

AbstractObjectivesCyanobacteria are an ancient phylum of prokaryotes that contain the class Oxyphotobacteria, the unique bacterial group able to perform oxygenic photosynthesis. This group has been extensively studied by phylogenomics during the last decade, notably because it is widely accepted that Cyanobacteria were responsible for the spread of photosynthesis to the eukaryotic domain. The aim of this study was to evaluate the fraction of the oxyphotobacterial diversity for which sequenced genomes are available for genomic studies. For this, we built a phylogenomic-constrained SSU rRNA (16S) tree to pinpoint unexploited clusters of Oxyphotobacteria that should be targeted for future genome sequencing, so as to improve our understanding of Oxyphotobacteria evolution.ResultsWe show that only a little fraction the oxyphotobacterial diversity has been sequenced so far. Indeed 31 rRNA clusters on the 60 composing the photosynthetic Cyanobacteria have a fraction of sequenced genomes <1%. This fraction remains low (min = 1%, median = 11.1 %, IQR = 7.3) within the remaining “‘sequenced” clusters that already contain some representative genomes. The “unsequenced” clusters are scattered across the whole Oxyphotobacteria tree, at the exception of very basal clades (G, F, E) and the Oscillatoriales clade (A), which have higher fractions of representative genomes. Yet, the very basal clades still feature some (sub)clusters without any representative genome. This last result is especially important, as these basal clades are prime candidate for plastid emergence.
Discovery of a human testis-specific protein complex TEX101-DPEP3 and selection of its disrupting antibodies
Authors: Schiza Christina , Korbakis Dimitrios , Panteleli Efstratia , Jarvi Keith , Drabovich Andrei P. , Diamandis Eleftherios P. 
Published: May 2018

SUMMARYTEX101 is a testis-specific protein expressed exclusively in male germ cells and is a validated biomarker of male infertility. Studies in mice suggest that TEX101 is a cell-surface chaperone which regulates, through protein-protein interactions, the maturation of proteins involved in spermatozoa transit and oocyte binding. Male TEX101-null mice are sterile. Here, we identified by co-immunoprecipitation-mass spectrometry the interactome of human TEX101 in testicular tissues and spermatozoa. The testis-specific cell-surface dipeptidase 3 (DPEP3) emerged as the top hit. We further validated the TEX101-DPEP3 complex by using hybrid immunoassays. Combinations of antibodies recognizing different epitopes of TEX101 and DPEP3 facilitated development of a simple immunoassay to screen for disruptors of TEX101-DPEP3 complex. As a proof-of-a-concept, we demonstrated that anti-TEX101 antibody T4 disrupted the native TEX101-DPEP3 complex. Disrupting antibodies may be used to study the human TEX101-DPEP3 complex, and to develop modulators for male fertility.Non-standard abbreviationsTEX101Testis-expressed sequence 101 proteinDPEP3Dipeptidase 3AC-MSAffinity capture-mass spectrometryco-IP-MSCoimmunoprecipitation-mass spectrometryGPIGlycosylphosphatidylinositolLFQLabel-free quantificationmAbMonoclonal antibodyNHSN-hydroxysuccinimidePRMParallel reaction monitoringPTMPosttranslational modificationSPSeminal plasmaSRMSelected reaction monitoringFDRfalse detection rate
Identification of TEX101 functional interactome through proteomic measurement of human spermatozoa homozygous for the missense variant rs35033974
Authors: Schiza Christina , Korbakis Dimitrios , Jarvi Keith , Diamandis Eleftherios P. , Drabovich Andrei P. 
Published: May 2018

SUMMARYTEX101 is a testis-specific cell-surface protein expressed exclusively in the male germ cells and a validated biomarker of male infertility. Mouse TEX101 was found essential for male fertility, and was suggested to function as a cell surface chaperone involved in maturation of proteins required for sperm migration and sperm-oocyte interaction. However, the precise functional role of human TEX101 is not known and cannot be studiedin vitrodue to the lack of human germ cell lines. Here, we genotyped 386 healthy fertile men and sub-fertile patients for a common and potentially deleterious missense variant rs35033974 ofTEX101, and identified 52 heterozygous and 4 homozygous patients. We then discovered by targeted proteomics that the variant allele rs35033974 was associated with near-complete degradation (>97%) of the corresponding G99V TEX101 form, and suggested that spermatozoa of homozygous patients could serve as a knockdown model to study TEX101 function in humans. Differential proteomic profiling with label-free quantification measured 8,046 proteins in spermatozoa of eight men and identified 8 cell-surface and 9 secreted testis-specific proteins significantly down-regulated in four patients homozygous for rs35033974. Substantially reduced levels of testis-specific cell-surface proteins potentially involved in sperm migration and sperm-oocyte fusion (including LY6K and ADAM29) were confirmed by targeted proteomics and western blotting assays. Since recent population-scale genomic data revealed homozygous fathers with biological children, rs35033974 is not a single pathogenic factor of male infertility in humans. However, median TEX101 levels in seminal plasma were found 5-fold lower (P=0.0005) in heterozygous than in wild-type men of European ancestry. We conclude that spermatozoa of rs35033974 homozygous men have substantially reduced levels of TEX101 and could be used as a model to elucidate the precise TEX101 function, which will advance biology of human reproduction.Non-standard abbreviationsTEX101Testis-expressed sequence 101 proteinLY6KLymphocyte antigen 6 complex locus KADAM29A disintegrin and metalloproteinase domain-containing protein 29DPEP3Dipeptidase 3BH-adjusted t-testBenjamini-Hochberg-adjusted t-testFDRFalse discovery rateFWHMFull width at half maximumGPIGlycosylphosphatidylinositolLC-MS/MSliquid chromatography - tandem mass spectrometryLFQLabel-free quantificationMSMass spectrometrymAbMonoclonal antibodyMWUMann Whitney Unpaired t-testPRMParallel reaction monitoringROC AUCReceiver operating characteristic area under the curveSCXstrong cation exchange chromatographySPseminal plasmaSNVSingle nucleotide variationSRMSelected reaction monitoringWTwild-type
Improving management strategies of plant diseases using sequential sensitivity analyses
Authors: Rimbaud Loup , Dallot Sylvie , Bruchou Claude , Thoyer Sophie , Jacquot Emmanuel , Soubeyrand Samuel , Thébaud Gaël 
Published: May 2018

ABSTRACTImprovement of management strategies of epidemics is often hampered by constraints on experiments at large spatiotemporal scales. A promising approach consists of modelling the biological epidemic process and human interventions, which both impact disease spread. However, few methods enable the simultaneous optimisation of the numerous parameters of sophisticated control strategies. To do so, we propose a heuristic approach (i.e., a practical improvement method approximating an optimal solution) based on sequential sensitivity analyses. In addition, we use an economic improvement criterion, based on the net present value, accounting for both the cost of the different control measures and the benefit generated by disease suppression. This work is motivated by sharka (caused by Plum pox virus), a vector-borne disease of prunus trees (especially apricot, peach and plum) whose management in orchards is mainly based on surveillance and tree removal. We identified the key parameters of a spatiotemporal model simulating sharka spread and control, and approximated optimal values for these parameters. The results indicate that the current French management of sharka efficiently controls the disease, but can be economically improved using alternative strategies that are identified and discussed. The general approach should help policymakers to design sustainable and cost-effective strategies for disease management.
Fine-scale resolution and analysis of runs of homozygosity in domestic dogs
Authors: Sams Aaron J. , Boyko Adam R. 
Published: May 2018

Abstract/SummaryInbreeding and consanguinity leave distinct genomic traces, most notably long genomic tracts that are identical by descent and completely homozygous. These runs of homozygosity (ROH) can contribute to inbreeding depression if they contain deleterious variants that are fully or partially recessive. Several lines of evidence have been used to show that long (> 5 megabase (Mb)) ROH are disproportionately likely to harbor deleterious variation, but the extent to which long versus short tracts contribute to autozygosity at loci known to be deleterious and recessive has not been studied.In domestic dogs, nearly 200 mutations are known to cause recessive diseases, most of which can be efficiently assayed using SNP arrays. By examining genome-wide data from over 200,000 markers, including 150 recessive disease variants, we built high-resolution ROH density maps for nearly 2,500 dogs, recording ROH down to 500 kilobases. We observed over 500 homozygous deleterious recessive genotypes in the panel, 90% of which overlapped with ROH inferred by GERMLINE. Although most of these genotypes were contained in ROH over 5 Mb in length, 14% were contained in short (0.5 - 2.5 Mb) tracts, a significant enrichment compared to the genetic background, suggesting that even short tracts are useful for computing inbreeding metrics like the coefficient of inbreeding estimated from ROH (FROH).In our dataset, FROH differed significantly both within and among dog breeds. All breeds harbored some regions of reduced genetic diversity due to drift or selective sweeps, but the degree of inbreeding and the proportion of inbreeding caused by short versus long tracts differed between breeds, reflecting their different population histories. Although only available for a few species, large genome-wide datasets including recessive disease variants hold particular promise not only for disentangling the genetic architecture of inbreeding depression, but also evaluating and improving upon current approaches for detecting ROH.