First Measurement Using Elliptically Polarized Photons of the Double-Polarization Observable E for γp→pπ

We report the measurement of the helicity asymmetry E for the pπ^{0} and nπ^{+} final states using, for the first time, an elliptically polarized photon beam in combination with a longitudinally polarized target at the Crystal Ball experiment at MAMI. The results agree very well with data that were taken with a circularly polarized photon beam, showing that it is possible to simultaneously measure polarization observables that require linearly (e.g., G) and circularly polarized photons (e.g., E) and a longitudinally polarized target. The new data cover a photon energy range 270-1400 MeV for the pπ^{0} final state (230-842 MeV for the nπ^{+} final state) and the full range of pion polar angles, θ, providing the most precise measurement of the observable E. A moment analysis gives a clear observation of the pη cusp in the pπ^{0} final state.

Clinical Knowledge Model for the Prevention of Healthcare-Associated Venous Thromboembolism.

Knowledge models inform organizational behavior through the logical association of documentation processes, definitions, data elements, and value sets. The development of a well-designed knowledge model allows for the reuse of electronic health record data to promote efficiency in practice, data interoperability, and the extensibility of data to new capabilities or functionality such as clinical decision support, quality improvement, and research. The purpose of this article is to describe the development and validation of a knowledge model for healthcare-associated venous thromboembolism prevention. The team used FloMap, an Internet-based survey resource, to compare metadata from six healthcare organizations to an initial draft model. The team used consensus decision-making over time to compare survey results. The resulting model included seven panels, 41 questions, and 231 values. A second validation step included completion of an Internet-based survey with 26 staff nurse respondents representing 15 healthcare organizations, two electronic health record vendors, and one academic institution. The final knowledge model contained nine Logical Observation Identifiers Names and Codes panels, 32 concepts, and 195 values representing an additional six panels (groupings), 15 concepts (questions), and the specification of 195 values (answers). The final model is useful for consistent documentation to demonstrate the contribution of nursing practice to the prevention of venous thromboembolism.

Hip Disorders in Bull Riders: Clinical Observations and Outcomes of Arthroscopy.

Bull riders represent a microcosm of athletes in whom severe consequences of femoroacetabular impingement may challenge the limits of arthroscopic intervention. Observations of this cohort may provide meaningful insight into the treatment of other populations. All patients undergoing hip arthroscopy are prospectively assessed with a modified Harris Hip Score. Sixteen consecutive bull riders (21 hips) with minimum 2-year follow-up are reported. The average age was 26 years, duration of symptoms was 33 months, and follow-up was 57 months. Arc of rotational hip motion averaged 31°. All had femoroacetabular impingement (17 combined and 4 cam impingements). Among the cam impingements, 1 also had dysplasia and 1 also had borderline dysplasia. Radiographic Tönnis grades were as follows: 2 Tönnis 1; 18 Tönnis 2; and 1 Tönnis 3. All had acetabular articular damage (14 Outerbridge grade 4; 6 Outerbridge grade 3; and 1 Outerbridge grade 1). Nine underwent microfracture. Four had accompanying femoral chondral lesions (3 grade 3; 1 grade 4). There were 20 labral tears (14 repaired and 6 debrided). All but 1 (95%) improved after surgery. One bilateral case underwent conversion to resurfacing arthroplasty on one side and revision arthroscopy on the other. The average improvement was 21.3 points. Thirteen (81.25%) returned to bull riding at an average of 7 months. Among the 3 who did not return, each had undergone bilateral procedures. There were no complications. Femoroacetabular impingement can be a significant problem among bull riders. Limited range of motion, grade 4 articular damage, and Tönnis 2 radiographic changes may not preclude successful arthroscopic treatment, but advanced bilateral disease may be too much even for these hardened athletes. [Orthopedics. 2024;47(2):79-82.].

Translating ethical and quality principles for the effective, safe and fair development, deployment and use of artificial intelligence technologies in healthcare.

OBJECTIVE: The complexity and rapid pace of development of algorithmic technologies pose challenges for their regulation and oversight in healthcare settings. We sought to improve our institution's approach to evaluation and governance of algorithmic technologies used in clinical care and operations by creating an Implementation Guide that standardizes evaluation criteria so that local oversight is performed in an objective fashion. MATERIALS AND METHODS: Building on a framework that applies key ethical and quality principles (clinical value and safety, fairness and equity, usability and adoption, transparency and accountability, and regulatory compliance), we created concrete guidelines for evaluating algorithmic technologies at our institution. RESULTS: An Implementation Guide articulates evaluation criteria used during review of algorithmic technologies and details what evidence supports the implementation of ethical and quality principles for trustworthy health AI. Application of the processes described in the Implementation Guide can lead to algorithms that are safer as well as more effective, fair, and equitable upon implementation, as illustrated through 4 examples of technologies at different phases of the algorithmic lifecycle that underwent evaluation at our academic medical center. DISCUSSION: By providing clear descriptions/definitions of evaluation criteria and embedding them within standardized processes, we streamlined oversight processes and educated communities using and developing algorithmic technologies within our institution. CONCLUSIONS: We developed a scalable, adaptable framework for translating principles into evaluation criteria and specific requirements that support trustworthy implementation of algorithmic technologies in patient care and healthcare operations.

Endoscopic Hip Abductor Tendon Repair Results in Successful Outcomes With 5- to 10-Year Follow-up.

PURPOSE: To report the outcomes of endoscopic repair in a consecutive series of patients with follow-up ranging from 5 to 10 years. METHODS: Sixty-five consecutive hips in 63 patients (2 bilateral) undergoing endoscopic abductor tendon repair with minimum 5-year follow-up were assessed with the modified Harris Hip Score. The minimal clinically important difference (MCID) was determined as one-half the standard deviation of the amount of improvement. RESULTS: The mean age was 56.6 years (standard deviation [SD], 11.3 years), with 58 female and 5 male patients. Follow-up was obtained on 64 hips (98.5%) at a mean of 85 months (SD, 15.7 months). There were 33 full-thickness and 32 partial-thickness tears, with 40 gluteus medius tears, 23 medius and minimus tears, and 2 isolated minimus tears. Concomitant arthroscopy of the hip joint was performed in 50 patients (52 hips), including 15 with correction of femoroacetabular impingement. The mean modified Harris Hip Score was 48.4 (SD, 15.7) preoperatively and 83.4 (SD, 15.9) postoperatively, reflecting a mean improvement of 34.9 (95% confidence interval, 34.9 ± 4.3), with 92.2% of patients achieving the MCID of 8.7. There were no complications. Three patients underwent further surgery: One underwent total hip replacement at 11 months after abductor repair, one underwent repeated arthroscopy for joint debridement at 12 months after repair, and one underwent revision abductor repair at 6 years postoperatively. CONCLUSIONS: Collectively, with 5- to 10-year follow-up, patients undergoing endoscopic abductor tendon repair can respond exceptionally well, with 92.2% achieving the MCID, even among a heterogeneous group of partial- and full-thickness tears with single- and 2-tendon involvement undergoing single- and double-row repair. LEVEL OF EVIDENCE: Level IV, case series.

Measured proton electromagnetic structure deviates from theoretical predictions.

The visible world is founded on the proton, the only composite building block of matter that is stable in nature. Consequently, understanding the formation of matter relies on explaining the dynamics and the properties of the proton's bound state. A fundamental property of the proton involves the response of the system to an external electromagnetic field. It is characterized by the electromagnetic polarizabilities1 that describe how easily the charge and magnetization distributions inside the system are distorted by the electromagnetic field. Moreover, the generalized polarizabilities2 map out the resulting deformation of the densities in a proton subject to an electromagnetic field. They disclose essential information about the underlying system dynamics and provide a key for decoding the proton structure in terms of the theory of the strong interaction that binds its elementary quark and gluon constituents. Of particular interest is a puzzle in the electric generalized polarizability of the proton that remains unresolved for two decades2. Here we report measurements of the proton's electromagnetic generalized polarizabilities at low four-momentum transfer squared. We show evidence of an anomaly to the behaviour of the proton's electric generalized polarizability that contradicts the predictions of nuclear theory and derive its signature in the spatial distribution of the induced polarization in the proton. The reported measurements suggest the presence of a new, not-yet-understood dynamical mechanism in the proton and present notable challenges to the nuclear theory.

Characterization of Senecavirus A Isolates Collected From the Environment of U.S. Sow Slaughter Plants.

Vesicular disease caused by Senecavirus A (SVA) is clinically indistinguishable from foot-and-mouth disease (FMD) and other vesicular diseases of swine. When a vesicle is observed in FMD-free countries, a costly and time-consuming foreign animal disease investigation (FADI) is performed to rule out FMD. Recently, there has been an increase in the number of FADIs and SVA positive samples at slaughter plants in the U.S. The objectives of this investigation were to: (1) describe the environmental burden of SVA in sow slaughter plants; (2) determine whether there was a correlation between PCR diagnostics, virus isolation (VI), and swine bioassay results; and (3) phylogenetically characterize the genetic diversity of contemporary SVA isolates. Environmental swabs were collected from three sow slaughter plants (Plants 1-3) and one market-weight slaughter plant (Plant 4) between June to December 2020. Of the 426 samples taken from Plants 1-3, 304 samples were PCR positive and 107 were VI positive. There was no detection of SVA by PCR or VI at Plant 4. SVA positive samples were most frequently found in the summer (78.3% June-September, vs. 59.4% October-December), with a peak at 85% in August. Eighteen PCR positive environmental samples with a range of Ct values were selected for a swine bioassay: a single sample infected piglets (n = 2). A random subset of the PCR positive samples was sequenced; and phylogenetic analysis demonstrated co-circulation and divergence of two genetically distinct groups of SVA. These data demonstrate that SVA was frequently found in the environment of sow slaughter plants, but environmental persistence and diagnostic detection was not indicative of whether a sampled was infectious to swine. Consequently, a more detailed understanding of the epidemiology of SVA and its environmental persistence in the marketing chain is necessary to reduce the number of FADIs and aide in the development of control measures to reduce the spread of SVA.

Measurement of Compton Scattering at MAMI for the Extraction of the Electric and Magnetic Polarizabilities of the Proton.

A precise measurement of the differential cross sections dσ/dΩ and the linearly polarized photon beam asymmetry Σ_{3} for Compton scattering on the proton below pion threshold has been performed with a tagged photon beam and almost 4π detector at the Mainz Microtron. The incident photons were produced by the recently upgraded Glasgow-Mainz photon tagging facility and impinged on a cryogenic liquid hydrogen target, with the scattered photons detected in the Crystal Ball/TAPS setup. Using the highest statistics Compton scattering data ever measured on the proton along with two effective field theories (both covariant baryon and heavy-baryon) and one fixed-t dispersion relation model, constraining the fits with the Baldin sum rule, we have obtained the proton electric and magnetic polarizabilities with unprecedented precision: α_{E1}=10.99±0.16±0.47±0.17±0.34, ß_{M1}=3.14±0.21±0.24±0.20±0.35; in units of 10^{-4} fm^{3} where the errors are statistical, systematic, spin polarizability dependent, and model dependent.

Survival of climate warming through niche shifts: Evidence from frogs on tropical islands.

How will organisms cope when forced into warmer-than-preferred thermal environments? This is a key question facing our ability to monitor and manage biota as average annual temperatures increase, and is of particular concern for range-limited terrestrial species unable to track their preferred climatic envelope. Being ectothermic, desiccation prone, and often spatially restricted, island-inhabiting tropical amphibians exemplify this scenario. Pre-Anthropocene case studies of how insular amphibian populations responded to the enforced occupation of warmer-than-ancestral habitats may add a valuable, but currently lacking, perspective. We studied a population of frogs from the Seychelles endemic family Sooglossidae which, due to historic sea-level rise, have been forced to occupy a significantly warmer island (Praslin) than their ancestors and close living relatives. Evidence from thermal activity patterns, bioacoustics, body size distributions, and ancestral state estimations suggest that this population shifted its thermal niche in response to restricted opportunities for elevational dispersal. Relative to conspecifics, Praslin sooglossids also have divergent nuclear genotypes and call characters, a finding consistent with adaptation causing speciation in a novel thermal environment. Using an evolutionary perspective, our study reveals that some tropical amphibians have survived episodes of historic warming without the aid of dispersal and therefore may have the capacity to adapt to the currently warming climate. However, two otherwise co-distributed sooglossid species are absent from Praslin, and the deep evolutionary divergence between the frogs on Praslin and their closest extant relatives (~8 million years) may have allowed for gradual thermal adaptation and speciation. Thus, local extinction is still a likely outcome for tropical frogs experiencing warming climates in the absence of dispersal corridors to thermal refugia.

UK experience of ofatumumab in recurrence of focal segmental glomerulosclerosis post-kidney transplant.

BACKGROUND: Steroid-resistant nephrotic syndrome (SRNS), commonly caused by focal segmental glomerulosclerosis (FSGS), is associated with progression to stage 5 chronic kidney disease, requirement for kidney replacement therapy and a risk of disease recurrence post-kidney transplantation. Ofatumumab (OFA) is a fully humanised monoclonal antibody to CD20, with similar mechanisms of action to rituximab (RTX). METHODS: We report a case series of seven UK patients (five paediatric, two adult), all of whom developed FSGS recurrence after kidney transplantation and received OFA as part of their therapeutic intervention. All also received concomitant plasmapheresis. The 2-year outcome of these seven patients is reported, describing clinical course, kidney function and proteinuria. RESULTS: Four patients (all paediatric) achieved complete urinary remission with minimal proteinuria 12 months post-treatment. Three of those four also had normal graft function. Two patients showed partial remission-brief improvement to non-nephrotic proteinuria (197 mg/mmol) in one patient, maintained improvement in kidney function (estimated glomerular filtration rate 76 ml/min/1.73 m2) in the other. One patient did not demonstrate any response. CONCLUSIONS: OFA may represent a useful addition to therapeutic options in the management of FSGS recurrence post-transplantation, including where RTX has shown no benefit. Concomitant plasmapheresis in all patients prevents any definitive conclusion that OFA was the beneficial intervention.

Methodology to Determine Cause of Death for Stillbirths and Neonatal Deaths Using Automated Case Reports and a Cause-of-Death Panel.

BACKGROUND: Review of data from multiple sources is often necessary to determine cause of death for stillbirths and neonatal deaths, especially in low- to middle-income countries (LMICs) where available data may vary. The minimally invasive tissue sampling (MITS) procedure provides granular histologic and microbiologic data that clinical reports and verbal autopsies cannot provide. Expert panel evaluation of data from individual deaths can be resource-intensive but remains essential to accurately infer causes of death. METHODS: The Project to Understand and Research Preterms and Stillbirths in South Asia (PURPOSe) study uses review panels to evaluate causes of death in 2 LMICs. To make the process manageable, a subset of the study variables was selected with professional input and organized into case reports. Case reports include clinical information, laboratory results, fetal or neonatal organ histology and polymerase chain reaction results from tissue obtained by MITS. Panelists evaluated the complete case report forms and then determined the cause of death based on available data. RESULTS: Computerized case reports averaged 2 to 3 pages. Approximately 6 to 8 cases were reviewed and discussed per 1-hour panel meeting. All panelists were provided the same information; missing data were noted. This limited bias between panelists and across meetings. Study teams notably took ownership of data quality. CONCLUSIONS: Standardized case reports for cause-of-death determination panel evaluation improve the efficiency of the review process, clarify available information, and limit bias across panelists, time, and location.

Single π 0 production off neutrons bound in deuteron with linearly polarized photons.

The quasifree γ → d → π 0 n ( p ) photon beam asymmetry, Σ , has been measured at photon energies, E γ , from 390 to 610 MeV, corresponding to center of mass energy from 1.271 to 1.424 GeV, for the first time. The data were collected in the A2 hall of the MAMI electron beam facility with the Crystal Ball and TAPS calorimeters covering pion center-of-mass angles from 49 ∘ to 148 ∘ . In this kinematic region, polarization observables are sensitive to contributions from the Δ ( 1232 ) and N(1440) resonances. The extracted values of Σ have been compared to predictions based on partial-wave analyses (PWAs) of the existing pion photoproduction database. Our comparison includes the SAID, MAID and Bonn-Gatchina analyses; while a revised SAID fit, including the new Σ measurements, has also been performed. In addition, isospin symmetry is examined as a way to predict π 0 n photoproduction observables, based on fits to published data in the channels π 0 p , π + n and π - p .

ICTV Virus Taxonomy Profile: Arteriviridae 2021.

The family Arteriviridae comprises enveloped RNA viruses with a linear, positive-sense genome of approximately 12.7 to 15.7 kb. The spherical, pleomorphic virions have a median diameter of 50-74 nm and include eight to eleven viral proteins. Arteriviruses infect non-human mammals in a vector-independent manner. Infections are often persistent and can either be asymptomatic or produce overt disease. Some arteriviruses are important veterinary pathogens while others infect particular species of wild rodents or African non-human primates. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Arteriviridae, which is available at ictv.global/report/arteriviridae.

Pre-Operative Antithyroid Antibodies in Differentiated Thyroid Cancer.

OBJECTIVE: To evaluate the significance of antithyroglobulin and antithyroid peroxidase antibody levels associated with locoregional metastatic disease in patients with well-differentiated thyroid cancer. METHODS: Patients underwent initial treatment for well-differentiated thyroid cancer at our institution between 2014 and 2018. The following variables were collected: age, sex, pre-operative thyroid-stimulating hormone, thyroglobulin, antithyroglobulin antibody (TgAb), antithyroid peroxidase antibody (TPOAb), the extent of surgery, T-stage, N-stage, extrathyroidal extension (ETE), extranodal extension (ENE), lymphovascular invasion, and multifocal disease. The relationships between disease status and pre-operative TPOAb, TgAb, thyroglobulin, and thyroid-stimulating hormone were analyzed. RESULTS: A total of 405 patients (mean age, 52 years) were included in the study, of which 66.4% were women. Elevated TgAb was associated with the presence of lymph node metastases (LNM) in both the central and lateral neck (P < .01), with a stronger correlation to N1b versus N1a disease (P = .03). The presence of ETE was inversely related to the TgAb titer (P = .03). TPOAb was associated with a lower T-stage (P = .04), fewer LNM (P = .04), and a lower likelihood of ETE (P = .02). From multivariable analysis, TgAb ≥40 IU/mL was an independent predictive factor for a higher N-stage (P < .01 for N0 vs N1; P = .01 for N1a vs N1b), and ENE (P < .01). TPOAb ≥60 IU/mL was associated with a lower T-stage (P = .04 for T <3) and absence of ETE (P = .01). CONCLUSION: Elevated pre-operative TgAb was an independent predictor of nodal metastases and ENE, while elevated TPOAb was associated with a lower pathologic T- and N-stage. Pre-operative antithyroid antibody titers may be useful to inform the disease extent and features.

Agroecology landscapes.

Context: Agroecology combines agronomic and ecological concepts. It relies on the enhancement of biodiversity and related ecosystem services to support agricultural production. It is dependent on biological interactions for the design and management of agricultural systems in agricultural landscapes. Objectives: We review the role of landscape ecology to understand and promote biodiversity, pest regulation and crop pollination for the designing of "agroecology landscapes". We illustrate the use of landscape ecological methods for supporting agroforestry systems as an example of agroecological development, and we propose pathways to implement agroecology at landscape scale. Methods: The state of the art of how landscape ecology contributes to agroecology development is summarized based on a literature review. Results: Agroecology requires thinking beyond the field scale to consider the positioning, quality and connectivity of fields and semi-natural habitats at larger spatial scales. The spatial and temporal organisation of semi-natural elements and the crop mosaic interact. Understanding this interaction is the pre-requisite for promoting patterns and mechanisms that foster biodiversity and ecosystem service provision. Promoting agroecological practices beyond individual farm borders can be rooted in a bottom-up approach from agroecological lighthouse farms to farm networks to amplify agroecology adoption at the landscape scale. Conclusions: Achieving agricultural landscapes composed of fields and farms following agroecological management requires understanding of biodiversity patterns, biological interactions and mechanisms that determine and boost ecosystem functioning to improve services at landscape scale, involving farmers in a bottom-up and context-specific approach.

Physical constraints and functional plasticity of cellulases.

Enzyme reactions, both in Nature and technical applications, commonly occur at the interface of immiscible phases. Nevertheless, stringent descriptions of interfacial enzyme catalysis remain sparse, and this is partly due to a shortage of coherent experimental data to guide and assess such work. In this work, we produced and kinetically characterized 83 cellulases, which revealed a conspicuous linear free energy relationship (LFER) between the substrate binding strength and the activation barrier. The scaling occurred despite the investigated enzymes being structurally and mechanistically diverse. We suggest that the scaling reflects basic physical restrictions of the hydrolytic process and that evolutionary selection has condensed cellulase phenotypes near the line. One consequence of the LFER is that the activity of a cellulase can be estimated from its substrate binding strength, irrespectively of structural and mechanistic details, and this appears promising for in silico selection and design within this industrially important group of enzymes.

Personalized tumor-specific DNA junctions to detect circulating tumor in patients with endometrial cancer.

INTRODUCTION: There are no reliable blood biomarkers for monitoring endometrial cancer patients in the current clinical practice. Circulating tumor DNA (ctDNA) is emerging as a promising non-invasive method to measure tumor burden, define prognosis and monitor disease status in many solid cancers. In this pilot study, we investigated if unique tumor-specific DNA junctions can be used to detect ctDNA levels in patients with endometrial cancer. METHODS: Chromosomal rearrangements in primary tumors of eleven patients with high-grade or advanced stage endometrial cancer were determined by whole-genome Mate-Pair sequencing. Identified unique tumor-specific junctions were evaluated in pre- and six-week post-surgery patient plasma using individualized quantitative polymerase chain reaction (qPCR) assays. The relationship between clinicopathological features and detection of ctDNA was investigated. RESULTS: CtDNA was detected in 60% (6/10) of cases pre-surgery and in 27% (3/11) post-surgery. The detection of ctDNA pre-surgery was consistent with clinical indicators of aggressive disease such as advanced stage (80% - 4/5), lymphatic spread of disease (100% - 3/3), serous histology (80% - 4/5), deep myometrial invasion (100% - 3/3), lympho-vascular space invasion (75% - 3/4). All patients in which ctDNA was detected post-surgically had type II endometrial cancer. DISCUSSION: This pilot study demonstrates the feasibility of using personalized tumor-specific junction panels for detecting ctDNA in the plasma of endometrial cancer patients. Larger studies and longer follow-up are needed to validate the potential association between pre-surgical ctDNA detection and the presence of cancers with aggressive pathologic tumor characteristics or advanced stage observed in this study.

Information Models Offer Value to Standardize Electronic Health Record Flowsheet Data: A Fall Prevention Exemplar.

PURPOSE: The rapid implementation of electronic health records (EHRs) resulted in a lack of data standardization and created considerable difficulty for secondary use of EHR documentation data within and between organizations. While EHRs contain documentation data (input), nurses and healthcare organizations rarely have useable documentation data (output). The purpose of this article is to describe a method of standardizing EHR flowsheet documentation data using information models (IMs) to support exchange, quality improvement, and big data research. As an exemplar, EHR flowsheet metadata (input) from multiple organizations was used to validate a fall prevention IM. DESIGN: A consensus-based, qualitative, descriptive approach was used to identify a minimum set of essential fall prevention data concepts documented by staff nurses in acute care. The goal was to increase generalizable and comparable nurse-sensitive data on the prevention of falls across organizations for big data research. METHODS: The research team conducted a retrospective, observational study using an iterative, consensus-based approach to map, analyze, and evaluate nursing flowsheet metadata contributed by eight health systems. The team used FloMap software to aggregate flowsheet data across organizations for mapping and comparison of data to a reference IM. The FloMap analysis was refined with input from staff nurse subject matter experts, review of published evidence, current documentation standards, Magnet Recognition nursing standards, and informal fall prevention nursing use cases. FINDINGS: Flowsheet metadata analyzed from the EHR systems represented 6.6 million patients, 27 million encounters, and 683 million observations. Compared to the original reference IM, five new IM classes were added, concepts were reduced by 14 (from 57 to 43), and 157 value set items were added. The final fall prevention IM incorporated 11 condition or age-specific fall risk screening tools and a fall event details class with 14 concepts. CONCLUSION: The iterative, consensus-based refinement and validation of the fall prevention IM from actual EHR fall prevention flowsheet documentation contributes to the ability to semantically exchange and compare fall prevention data across multiple health systems and organizations. This method and approach provides a process for standardizing flowsheet data as coded data for information exchange and use in big data research. CLINICAL RELEVANCE: Opportunities exist to work with EHR vendors and the Office of the National Coordinator for Health Information Technology to implement standardized IMs within EHRs to expand interoperability of nurse-sensitive data.

Computing Cellulase Kinetics with a Two-Domain Linear Interaction Energy Approach.

While heterogeneous enzyme reactions play an essential role in both nature and green industries, computational predictions of their catalytic properties remain scarce. Recent experimental work demonstrated the applicability of the Sabatier principle for heterogeneous biocatalysis. This provides a simple relationship between binding strength and the catalytic rate and potentially opens a new way for inexpensive computational determination of kinetic parameters. However, broader implementation of this approach will require fast and reliable prediction of binding free energies of complex two-phase systems, and computational procedures for this are still elusive. Here, we propose a new framework for the assessment of the binding strengths of multidomain proteins, in general, and interfacial enzymes, in particular, based on an extended linear interaction energy (LIE) method. This two-domain LIE (2D-LIE) approach was successfully applied to predict binding and activation free energies of a diverse set of cellulases and resulted in robust models with high accuracy. Overall, our method provides a fast computational screening tool for cellulases that have not been experimentally characterized, and we posit that it may also be applicable to other heterogeneously acting biocatalysts.

Comparison of historical and contemporary isolates of Senecavirus A.

Senecavirus A (SVA) was discovered as a cell culture contaminant in 2002, and multiple attempts to experimentally reproduce disease were unsuccessful. Field reports of porcine idiopathic vesicular disease (PIVD) cases testing PCR positive for SVA in addition to outbreaks of PIVD in Brazil and the United States in 2015 suggested SVA was a causative agent, which has now been consistently demonstrated experimentally. Ease of experimental reproduction of disease with contemporary strains of SVA raised questions concerning the difficulty of reproducing vesicular disease with historical isolates. The following study was conducted to compare the pathogenicity of SVA between historical and contemporary isolates in growing pigs. Six groups of pigs (n = 8) were intranasally inoculated with the following SVA isolates: SVV001/2002, CAN/2011, HI/2012, IA/2015, NC/2015, SD/2015. All isolates induced vesicular disease in at least half of the inoculated pigs from each group. All pigs replicated virus as demonstrated by serum and/or swab samples positive for SVA by quantitative PCR. Pig sera tested by virus neutralization assay demonstrated cross-neutralizing antibodies against all viruses utilized in the study. Cross-neutralizing antibodies from pigs inoculated with historical isolates were lower than those pigs that were inoculated with contemporary isolates. Phylogenetic analysis revealed two clades with SVV001/2002 being in a separate clade compared to the other five isolates. Although differences in the infection kinetics and sequences of these six isolates were found, clinical presentation of vesicular disease was similar between both historical and contemporary isolates.