Unique characteristics of the J-domain proximal regions of Hsp70 cochaperone Apj1 in prion propagation/elimination and its overlap with Sis1 function.

J-domain proteins (JDPs) are obligate cochaperones of Hsp70s. The Class A JDP Apj1 of the yeast cytosol has an unusually complex region between the N-terminal J-domain and the substrate binding region-often called the Grich or GF region in Class A and B JDPs because of its typical abundance of glycine. The N-terminal 161-residue Apj1 fragment is known to be sufficient for Apj1 function in prion curing, driven by the overexpression of Hsp104. Further analyzing the N-terminal segment of Apj1, we found that a 90-residue fragment that includes the 70-residue J-domain and the adjacent 12-residue glutamine/alanine (Q/A) segment is sufficient for curing. Furthermore, the 121-residue fragment that includes the Grich region was sufficient to not only sustain the growth of cells lacking the essential Class B JDP Sis1 but also enabled the maintenance of several prions normally dependent on Sis1 for propagation. A J-domain from another cytosolic JDP could substitute for the Sis1-related functions but not for Apj1 in prion curing. Together, these results separate the functions of JDPs in prion biology and underscore the diverse functionality of multi-domain cytosolic JDPs in yeast.

Hyperdiluted Botulinum Toxin and Intense Pulsed Light Treatment: A Case Series to Illustrate a Novel Protocol for Hypertrophic Scar Reduction.

Hypertrophic scars can have significant and far-reaching effects on patients that range from itching to creating difficulty with mobility, all of which can negatively impact the individual's quality of life. A recent study showed that many patients with recent scars report pain, burning, pruritus, erythema, in combination with psychological difficulties that impact bodily movement, choice of clothing, and participation in leisure activities. Botulinum toxin Type A (BoNTA) and intense pulsed light (IPL) have shown promise in treating such scars. We propose a novel treatment protocol involving a 4-week intervention with hyperdiluted BoNTA injections and supplemental treatment with IPL for erythema, and a 6-month scar scale assessment and photographic documentation that occurs before and 6 months after treatment. We report four cases where using hyperdiluted BoNTA, either alone or in conjunction with IPL, substantially reduced scar size, improved overall scar appearance, and diminished erythema in areas on the face and the breasts. Although this report suggests that a schedule of alternating treatments with BoNTA and IPL may be beneficial in reducing scar size and enhancing appearance, further research is necessary to better understand the most effective dosages, the relationship between BoNTA and IPL, and the optimal management of scarring.

Using explainable machine learning methods to evaluate vulnerability and restoration potential of ecosystem state transitions.

Ecosystem state transitions can be ecologically devastating or be a restoration success. State transitions are common within aquatic systems worldwide, especially considering human-mediated changes to land use and water use. We created a transferable conceptual framework to enable multiscale assessments of state resilience and early warnings of state transitions that can inform strategic restorations and avoid ecosystem collapse. The conceptual framework integrated machine learning predictions with ecosystem state concepts (e.g., state classification, gradients of vulnerability, and recovery potential leading to state transitions) and was devised to investigate possible environmental drivers. As an application of the framework, we generated prediction probabilities of submersed aquatic vegetation (SAV) presence at nearly 10,000 sites in the Upper Mississippi River (United States). Then, we used an interpretability method to explain model predictions to gain insights into possible environmental drivers and thresholds or linear responses of SAV presence and absence. Model accuracy was 89% without spatial bias. Average water depth, suspended solids, substrate, and distance to nearest SAV were the best predictors and likely environmental drivers of SAV habitat suitability. These environmental drivers exhibited nonlinear, threshold-type responses for SAV. All the results are also presented in an online dashboard to explore results at many spatial scales. The habitat suitability model outputs and prediction explanations from many spatial scales (4 m to 400 km of river reach) can inform research and restoration planning.

Métodos de aprendizaje automático para evaluar la vulnerabilidad y el potencial de restauración de las transiciones de estados de los ecosistemas Resumen Las transiciones de estado de los ecosistemas pueden tener consecuencias ecológicas graves o ser un éxito de restauración. Estas transiciones son comunes en los sistemas acuáticos, especialmente si consideramos los cambios mediados por humanos en el uso del suelo y del agua. Generamos un marco conceptual transferible para permitir las evaluaciones multiescalares de la resiliencia del estado y las alertas tempranas de la transición de estado que sirvan para guiar las restauraciones estratégicas y evitar el colapso del ecosistema. Este marco integró predicciones de aprendizaje automático a los conceptos de estado del ecosistema (p. ej.: clasificación del estado, gradientes de vulnerabilidad y potencial de restauración que lleve a transiciones de estado) y fue diseñado para investigar los posibles factores ambientales. Para aplicar el marco, generamos probabilidades de predicción de la presencia de vegetación acuática sumergida (VAS) en casi 10,000 sitios del Alto Río Mississippi en los Estados Unidos. Después usamos un método de interpretabilidad para explicar las predicciones del modelo y obtener información de los posibles factores ambientales y umbrales o respuestas lineales de la presencia y ausencia de la VAS. La precisión del modelo fue de 89% sin sesgo espacial. Los mejores pronosticadores y probables factores ambientales de la idoneidad de hábitat de la VAS fueron la profundidad promedio del agua, los sólidos suspendidos, el sustrato y la distancia a la VAS más cercana. Estos factores ambientales exhibieron respuestas no lineales de tipo umbral para la VAS. Todos los resultados también están presentados en un tablero virtual para explorar los resultados a varias escalas espaciales. Los resultados del modelo de idoneidad de hábitat y las explicaciones de las predicciones de varias de las escalas espaciales (4 m-400 km de alcance del río) pueden guiar la investigación y la planeación de la restauración.

A rapid, high-throughput, viral infectivity assay using automated brightfield microscopy with machine learning.

Infectivity assays are essential for the development of viral vaccines, antiviral therapies, and the manufacture of biologicals. Traditionally, these assays take 2-7 days and require several manual processing steps after infection. We describe an automated viral infectivity assay (AVIATM), using convolutional neural networks (CNNs) and high-throughput brightfield microscopy on 96-well plates that can quantify infection phenotypes within hours, before they are manually visible, and without sample preparation. CNN models were trained on HIV, influenza A virus, coronavirus 229E, vaccinia viruses, poliovirus, and adenoviruses, which together span the four major categories of virus (DNA, RNA, enveloped, and non-enveloped). A sigmoidal function, fit between virus dilution curves and CNN predictions, results in sensitivity ranges comparable to or better than conventional plaque or TCID50 assays, and a precision of ∼10%, which is considerably better than conventional infectivity assays. Because this technology is based on sensitizing CNNs to specific phenotypes of infection, it has potential as a rapid, broad-spectrum tool for virus characterization, and potentially identification.

In Science Journals.

Highlights from the Science family of journals.

Acquisition of High Spectral Resolution Diffuse Reflectance Image Cubes (350-2500 nm) from Archaeological Wall Paintings and Other Immovable Heritage Using a Field-Deployable Spatial Scanning Reflectance Spectrometry Hyperspectral System.

There is growing interest in bringing non-invasive laboratory-based analytical imaging tools to field sites to study wall paintings in order to collect molecular information on the macroscale. Analytical imaging tools, such as reflectance imaging spectrometry, have provided a wealth of information about artist materials and working methods, as well as painting conditions. Currently, scientific analyses of wall paintings have been limited to point-measurement techniques such as reflectance spectroscopy (near-ultraviolet, visible, near-infrared, and mid-infrared), X-ray fluorescence, and Raman spectroscopy. Macroscale data collection methods have been limited to multispectral imaging in reflectance and luminescence modes, which lacks sufficient spectral bands to allow for the mapping and identification of artist materials of interest. The development of laboratory-based reflectance and elemental imaging spectrometers and scanning systems has sparked interest in developing truly portable versions, which can be brought to field sites to study wall paintings where there is insufficient space or electrical power for laboratory instruments. This paper presents the design and testing of a simple hyperspectral system consisting of a 2D spatial spot scanning spectrometer, which provides high spectral resolution diffuse reflectance spectra from 350 to 2500 nm with high signal to noise and moderate spatial resolution (few mm). This spectral range at high spectral resolution was found to provide robust chemical specificity sufficient to identify and map many artists' materials, as well as the byproducts of weathering and conservation coatings across the surface of ancient and Byzantine Cypriot wall paintings. Here, we present a detailed description of the hyperspectral system, its performance, and examples of its use to study wall paintings from Roman tombs in Cyprus. The spectral/spatial image processing workflow to make maps of pigments and constituent painting materials is also discussed. This type of configurable hyperspectral system and the imaging processing workflow offer a new tool for the field study of wall paintings and other immovable heritage.

Reflectance Imaging Spectroscopy (RIS) for Operation Night Watch: Challenges and Achievements of Imaging Rembrandt's Masterpiece in the Glass Chamber at the Rijksmuseum.

Visible and infrared reflectance imaging spectroscopy is one of the several non-invasive techniques used during Operation Night Watch for the study of Rembrandt's iconic masterpiece The Night Watch (1642). The goals of this project include the identification and mapping of the artists' materials, providing information about the painting technique used as well as documenting the painting's current state and ultimately determining the possible conservation plan. The large size of the painting (3.78 m by 4.53 m) and the diversity of the technical investigations being performed make Operation Night Watch the largest research project ever undertaken at the Rijksmuseum. To construct a complete reflectance image cube at a high spatial resolution (168 µm2) and spectral resolution (2.54 to 6 nm), the painting was imaged with two high-sensitivity line scanning hyperspectral cameras (VNIR 400 to 1000 nm, 2.54 nm, and SWIR 900 to 2500 nm, 6 nm). Given the large size of the painting, a custom computer-controlled 3-D imaging frame was constructed to move each camera, along with lights, across the painting surface. A third axis, normal to the painting, was added along with a distance-sensing system which kept the cameras in focus during the scanning. A total of 200 hyperspectral image swaths were collected, mosaicked and registered to a high-resolution color image to sub-pixel accuracy using a novel registration algorithm. The preliminary analysis of the VNIR and SWIR reflectance images has identified many of the pigments used and their distribution across the painting. The SWIR, in particular, has provided an improved visualization of the preparatory sketches and changes in the painted composition. These data sets, when combined with the results from the other spectral imaging modalities and paint sample analyses, will provide the most complete understanding of the materials and painting techniques used by Rembrandt in The Night Watch.

Low-Cost Multispectral System Design for Pigment Analysis in Works of Art.

To better understand and preserve works of art, knowledge is needed about the pigments used to create the artwork. Various noninvasive techniques have been used previously to create pigment maps, such as combining X-ray fluorescence and hyperspectral imaging data. Unfortunately, most museums have limited funding for the expense of specialized research equipment, such as hyperspectral reflectance imaging systems. However, many museums have hand-held point X-ray fluorescence systems attached to motorized easels for scanning artwork. To assist museums in acquiring data that can produce similar results to that of HSI systems, while minimizing equipment costs, this study designed and modeled a prototype system to demonstrate the expected performance of a low-cost multispectral system that can be attached to existing motorized easels. We show that multispectral systems with a well-chosen set of spectral bands can often produce classification maps with value on par with hyperspectral systems. This study analyzed the potential for capturing data with a point scanning system through predefined filters. By applying the system and noise modeling parameters to HSI data captured from a 14th-Century illumination, the study reveals that the proposed multispectral imaging system is a viable option for this need.

'It's quite a complex trail for families now' - Provider understanding of access to services for Aboriginal children with a disability.

Aboriginal and Torres Strait Islander children experience a higher prevalence of disability and socio-economic disadvantage than other Australian children. Early intervention from across the health, education and social service sectors is vital for improving outcomes, but families face a number of barriers to service access which impede intervention. This study aimed to inform ways to improve access to services for families of urban-dwelling Aboriginal children with a range of disabilities. A qualitative approach was taken to explore providers' perceptions of factors that either impeded or enabled families' access to services. In this research, the term 'provider' refers to individuals who are employed in a range of sectors to deliver a service involving assessment or management of an individual with a disability. Semi-structured in-depth interviews with 24 providers were conducted. Data analysis was informed by the general inductive approach and then applied deductively to the candidacy framework to generate additional insights. Candidacy focuses on how potential users access the services they need and acknowledges the joint negotiation between families and providers regarding such access. Our research identified that candidacy was influenced by the historical legacy of colonisation and its ongoing socio-cultural impact on Aboriginal people, as well as funding and current policy directives. Enacting culturally sensitive and meaningful engagement to better understand families' needs and preferences for support, as well as support for providers to develop their understanding of family contexts, will contribute to facilitating service access for Aboriginal children with a disability.

Native Ureter Ventriculo-Ureteral Shunt Placement for Management of Refractory Hydrocephalus in a Child With a History of Renal Transplant: Case Report and Technical Note.

This report describes the case of a 5-year-old male with intractable hydrocephalus secondary to neonatal intraventricular hemorrhage who was ultimately managed with the placement of a ventriculo-ureteral (VU) shunt. He had previously failed numerous attempts at cerebrospinal fluid shunting, choroid plexus cauterization, and endoscopic third ventriculostomy. The patient had a history of end stage renal disease, and had previously undergone renal transplant. In an operation that involved Neurosurgeons, Pediatric Urologists, and Transplant surgeons, a Gibson incision was used to avoid the patient's multiple intra-abdominal adhesions, and his nonfunctioning renal unit was used to implant a VU shunt without early or late complications.

Dual mode standoff imaging spectroscopy documents the painting process of the Lamb of God in the Ghent Altarpiece by J. and H. Van Eyck.

The ongoing conservation treatment program of the Ghent Altarpiece by Hubert and Jan Van Eyck, one of the iconic paintings of the west, has revealed that the designs of the paintings were changed several times, first by the original artists, and then during later restorations. The central motif, The Lamb of God, representing Christ, plays an essential iconographic role, and its depiction is important. Because of the prevalence of lead white, it was not possible to visualize the Van Eycks' original underdrawing of the Lamb, their design changes, and the overpaint by later restorers with a single spectral imaging modality. However, by using elemental (x-ray fluorescence) and molecular (infrared reflectance) imaging spectroscopies, followed by analysis of the resulting data cubes, the necessary chemical contrast could be achieved. In this way, the two complementary modalities provided a more complete picture of the development and changes made to the Lamb.

Incidence and outcomes of aortic dissection for emergency departments in New South Wales, Australia 2017-2018: A data linkage study.

OBJECTIVE: The aims of the present study were to describe the age-specific incidence and 30-day mortality of aortic dissection patients presenting to the EDs in New South Wales (NSW). METHODS: This was a data linkage study involving emergency, inpatient and death registry administrative data from NSW. RESULTS: The present study found 273 instances of aortic dissection in NSW from July 2017 to July 2018. Calculated incidence was 3.47 per 100 000. Incidence increased exponentially with age. The 30-day mortality rate among this cohort was 35.53% (n = 97). Mortality was significantly associated with age and pre-existing comorbidity burden, but was not associated with gender, level of hospital or time of presentation. CONCLUSIONS: The present study found the incidence of aortic dissection within the NSW population to be 3.4 per 100 000. The incidence of aortic dissection in our population increased from 8.6 per 100 000 for people aged between 60 and 80 years to 32 per 100 000 for those aged over 80 years.

Molecular Fluorescence Imaging Spectroscopy for Mapping Low Concentrations of Red Lake Pigments: Van†Gogh's Painting The Olive Orchard.

Vincent van Gogh used fugitive red lake pigments that have faded in some paintings. Mapping their distribution is key to understanding how his paintings have changed with time. While red lake pigments can be identified from microsamples, in situ identification and mapping remain challenging. This paper explores the ability of molecular fluorescence imaging spectroscopy to identify and, more importantly, map residual non-degraded red lakes. The high sensitivity of this method enabled identification of the emission spectra of eosin (tetrabromine fluorescein) lake mixed with lead or zinc white at lower concentrations than elemental X-ray fluorescence (XRF) spectroscopy used on account of bromine. The molecular fluorescence mapping of residual eosin and two carmine red lakes in van Gogh's The Olive Orchard is demonstrated and compared with XRF imaging spectroscopy. The red lakes are consistent with the composition of paint tubes known to have been used by van Gogh.

Protocolization of Post-Transforaminal Lumbar Interbody Fusion Pain Control with Elimination of Benzodiazepines and Long-Acting Opioids.

BACKGROUND: The opioid epidemic continues to worsen with a concomitant increase in opioid-related mortality. In response, the Department of Defense and Veterans Health Agency recommended against the use of long-acting opioids (LAOs) and concurrent use of opioids with benzodiazepines. Subsequently, we eliminated benzodiazepines and LAOs from our postoperative pain control regimen. OBJECTIVE: To evaluate the impact of removing benzodiazepines and LAOs on postoperative pain in single-level transforaminal lumbar interbody fusion (TLIF) patients. METHODS: A retrospective cohort study of single-level TLIF patients from February 2016-March 2018 was performed. Postoperative pain control in the + benzodiazepine cohort included scheduled diazepam with or without LAOs. These medications were replaced with nonbenzodiazepine, opioid-sparing adjuncts in the -benzodiazepine cohort. Pain scores, length of hospitalization, trigger medication use, and opioid use and duration were compared. RESULTS: Among 77 patients, there was no difference between inpatient pain scores, but the -benzodiazepine cohort experienced a faster rate of morphine equivalent reduction (-18.7%, 95% CI [-1.22%, -36.10%]), used less trigger medications (-1.55, 95% CI [-0.43, -2.67]), and discharged earlier (0.6 d; 95% CI [0.01, 1.11 d]). As outpatients, the -benzodiazepine cohort was less likely to receive opioid refills at 2 wk (29.2% vs 55.8%, P = .021) and 6 mo postoperatively (0% vs 13.2%, P = .039), and was less likely to be using opioids by 3 mo postoperatively (13.3% vs 34.2%, P = .048). CONCLUSION: Replacement of benzodiazepines and LAOs in the pain control regimen for single-level TLIFs did not affect pain scores and was associated with decreased opioid use, a reduction in trigger medications, and shorter hospitalizations.

Collaborating across sectors to provide early intervention for Aboriginal and Torres Strait Islander children with disability and their families: a qualitative study of provider perspectives.

Aboriginal and Torres Strait Islander children experience a higher prevalence of disability than other Australian children. Early intervention from across the health, education, and social service sectors is vital for improving outcomes, but families face lack of coordination between services. This study aimed to inform improvements in service access for families of urban-dwelling Aboriginal children with disability through exploring providers' perceptions of factors that influenced working together across sectors. Semi-structured interviews were conducted. Data analysis was informed by the general inductive approach and the Collaborative Practice to Enhance Patient Care Outcomes framework. Twenty-four providers participated. Interprofessional collaborative practice was influenced by interdependent interactional and organizational factors. Interactional factors fit within one of two dimensions: the ability of providers to share common goals and vision within a complex cross-sector service landscape, and influence of interpersonal relationships on their sense of belonging working in a cross-cultural space. Organizational factors also fit within one of two dimensions: the influence of governance in relation to its role in coordination and unlocking the strength of schools as service settings, and the need to formalize processes for effective interprofessional communication. Interprofessional collaborative practice was managed within the context of systemic factors relating to policy and funding. These findings demonstrate the complex interplay of factors related to the cross-sector involvement of providers in early intervention service provision. Consideration of these factors is required to facilitate collaborative cross-sector responses to improve service access for Aboriginal families.Abbreviations: WHO: world health organization; ACCHS: aboriginal community controlled health service; GP: general practitioner; NDIS: national disability insurance scheme.

Dual Invasive Fungal Infection Presenting with Cervical Myelopathy.

Disseminated fungal infections are often seen in immunocompromised patients. Here we present a case of a previously healthy woman presenting with cervical myeloradiculopathy found to have two separate fungal infections in the setting of depressed CD4 cell counts and a genetic mutation predisposing to invasive fungal infections.

Ankle Fracture Stability-Based Classification: A Study of Reproducibility and Clinical Prognostic Ability.

OBJECTIVE: To compare the reproducibility and prognostic capacity of 2 commonly used ankle fracture classifications to the stability-based classification. METHODS: One hundred ninety-three consecutive rotational-type ankle fractures treated during a year at our institution in patients older than 18 years were retrospectively analyzed. Pilon and pathologic fractures were excluded. The fractures were treated by attending physicians who were unaware of the stability-based classification system. Three observers classified injury radiographs using the Lauge-Hansen, Weber/AO, and stability-based classifications systems. Reproducibility (interobserver variation) of each classification system was calculated using kappa statistics. Prognostic values were evaluated by calculating the area under the curve for the receiver-operating characteristic curves (using surgery as the positive outcome). RESULTS: The stability-based and Weber/AO classifications showed better reproducibility [kappa 0.938 (95% confidence interval 0.921-0.952), kappa 0.97 (0.961-0.976)], respectively, than the Lauge-Hansen [kappa 0.74 (0.664-0.795); P < 0.05]. The stability-based classification was more accurate (P < 0.001) in predicting surgical treatment [area under the curve 0.883 (95% confidence interval 0.852-0.914)] compared with the other 2 classifications [0.626 (0.576-0.675) and 0.698 (0.641-0.755)], respectively. CONCLUSIONS: The stability-based classification was both highly reproducible (kappa 0.938) and had superior prognostic capacity to identify patients who needed surgical intervention compared with both the Lauge-Hansen and AO/Weber classification systems. Importantly, there were no patients who were classified as stable who failed nonoperative treatment. This extends earlier studies by directly demonstrating its prognostic advantage to other classification systems.

Risk of bias judgements and strength of conclusions in meta-evidence from the Cochrane Colorectal Cancer Group.

BACKGROUND: The Cochrane Collaboration records risk of bias (ROB) judgements on the original studies it analyses. The aim of this review is to perform an audit of all literature produced by the Cochrane Colorectal Cancer Group (CCCG), focusing on whether intervention type has any relationship with ROB and the ability of a review to inform clinical practice. METHODS: The most recent version of every CCCG review from January 2000 to the end of July 2018 was included. Conclusions were categorized as informing clinical practice (I) or not (N). Both I and N categories were divided into firm (F) or tempered (T) based on the definitiveness of their language. ROB judgements were aggregated. Reviews were classed as Medical (M), Surgical (S), Medical & Surgical (MS) or Other (O) based on their intervention, with O reviews then excluded. Data were analyzed in SPSS. RESULTS: Ninety-five reviews were included, covering 1892 studies. Sixty-two percent (n = 59/95) informed clinical practice (I). Thirty-eight percent (n = 36/95) did not inform clinical practice (N). Of the N group, 53% (n = 19/36) were completely equivocal (firm) while 47% (n = 17/36) were moderately so (tempered). In the I group, 46% (n = 27/59) gave a conclusion that was firm and 54% (n = 32/59) were tempered. Seven thousand five hundred sixty-four cases of bias were assessed. Risk of bias was low in 43%, high in 20% and unclear in 37%. A review that regarded a medical intervention alone was significantly more likely to be comprised of studies with a low risk of bias than a review that included a surgical intervention (p < 0.001). CONCLUSION: The Cochrane Colorectal Cancer Group finds the risk of bias to be low in less than half of its judgements. A review that included a surgical intervention was less likely to display low risk of bias. Risk of bias was associated with whether a review informed clinical practice, but intervention type was not. Readers of colorectal literature should be cautious when considering original and meta-evidence in this field, particularly where a surgical intervention is assessed.

Correction: Fucoidans inhibit the formation of post-operative abdominal adhesions in a rat model.

[This corrects the article DOI: 10.1371/journal.pone.0207797.].