Preclinical evaluation of two phylogenetically distant arenavirus vectors for the development of novel immunotherapeutic combination strategies for cancer treatment.

BACKGROUND: Engineered arenavirus vectors have recently been developed to leverage the body's immune system in the fight against chronic viral infections and cancer. Vectors based on Pichinde virus (artPICV) and lymphocytic choriomeningitis virus (artLCMV) encoding a non-oncogenic fusion protein of human papillomavirus (HPV)16 E6 and E7 are currently being tested in patients with HPV16+ cancer, showing a favorable safety and tolerability profile and unprecedented expansion of tumor-specific CD8+ T cells. Although the strong antigen-specific immune response elicited by artLCMV vectors has been demonstrated in several preclinical models, PICV-based vectors are much less characterized. METHODS: To advance our understanding of the immunobiology of these two vectors, we analyzed and compared their individual properties in preclinical in vivo and in vitro systems. Immunogenicity and antitumor effect of intratumoral or intravenous administration of both vectors, as well as combination with NKG2A blockade, were evaluated in naïve or TC-1 mouse tumor models. Flow cytometry, Nanostring, and histology analysis were performed to characterize the tumor microenvironment (TME) and T-cell infiltrate following treatment. RESULTS: Despite being phylogenetically distant, both vectors shared many properties, including preferential infection and activation of professional antigen-presenting cells, and induction of potent tumor-specific CD8+ T-cell responses. Systemic as well as localized treatment induced a proinflammatory shift in the TME, promoting the infiltration of inducible T cell costimulator (ICOS)+CD8+ T cells capable of mediating tumor regression and prolonging survival in a TC-1 mouse tumor model. Still, there was evidence of immunosuppression built-up over time, and increased expression of H2-T23 (ligand for NKG2A T cell inhibitory receptor) following treatment was identified as a potential contributing factor. NKG2A blockade improved the antitumor efficacy of artARENA vectors, suggesting a promising new combination approach. This demonstrates how detailed characterization of arenavirus vector-induced immune responses and TME modulation can inform novel combination therapies. CONCLUSIONS: The artARENA platform represents a strong therapeutic vaccine approach for the treatment of cancer. The induced antitumor immune response builds the backbone for novel combination therapies, which warrant further investigation.

A bench-top Dark-Root device built with LEGO® bricks enables a non-invasive plant root development analysis in soil conditions mirroring nature.

Roots are the hidden parts of plants, anchoring their above-ground counterparts in the soil. They are responsible for water and nutrient uptake and for interacting with biotic and abiotic factors in the soil. The root system architecture (RSA) and its plasticity are crucial for resource acquisition and consequently correlate with plant performance while being highly dependent on the surrounding environment, such as soil properties and therefore environmental conditions. Thus, especially for crop plants and regarding agricultural challenges, it is essential to perform molecular and phenotypic analyses of the root system under conditions as near as possible to nature (#asnearaspossibletonature). To prevent root illumination during experimental procedures, which would heavily affect root development, Dark-Root (D-Root) devices (DRDs) have been developed. In this article, we describe the construction and different applications of a sustainable, affordable, flexible, and easy to assemble open-hardware bench-top LEGO® DRD, the DRD-BIBLOX (Brick Black Box). The DRD-BIBLOX consists of one or more 3D-printed rhizoboxes, which can be filled with soil while still providing root visibility. The rhizoboxes sit in a scaffold of secondhand LEGO® bricks, which allows root development in the dark and non-invasive root tracking with an infrared (IR) camera and an IR light-emitting diode (LED) cluster. Proteomic analyses confirmed significant effects of root illumination on barley root and shoot proteomes. Additionally, we confirmed the significant effect of root illumination on barley root and shoot phenotypes. Our data therefore reinforces the importance of the application of field conditions in the lab and the value of our novel device, the DRD-BIBLOX. We further provide a DRD-BIBLOX application spectrum, spanning from investigating a variety of plant species and soil conditions and simulating different environmental conditions and stresses, to proteomic and phenotypic analyses, including early root tracking in the dark.

Immunogenetics associated with severe coccidioidomycosis.

Disseminated coccidioidomycosis (DCM) is caused by Coccidioides, pathogenic fungi endemic to the southwestern United States and Mexico. Illness occurs in approximately 30% of those infected, less than 1% of whom develop disseminated disease. To address why some individuals allow dissemination, we enrolled patients with DCM and performed whole-exome sequencing. In an exploratory set of 67 patients with DCM, 2 had haploinsufficient STAT3 mutations, and defects in ß-glucan sensing and response were seen in 34 of 67 cases. Damaging CLEC7A and PLCG2 variants were associated with impaired production of ß-glucan-stimulated TNF-α from PBMCs compared with healthy controls. Using ancestry-matched controls, damaging CLEC7A and PLCG2 variants were overrepresented in DCM, including CLEC7A Y238* and PLCG2 R268W. A validation cohort of 111 patients with DCM confirmed the PLCG2 R268W, CLEC7A I223S, and CLEC7A Y238* variants. Stimulation with a DECTIN-1 agonist induced DUOX1/DUOXA1-derived hydrogen peroxide [H2O2] in transfected cells. Heterozygous DUOX1 or DUOXA1 variants that impaired H2O2 production were overrepresented in discovery and validation cohorts. Patients with DCM have impaired ß-glucan sensing or response affecting TNF-α and H2O2 production. Impaired Coccidioides recognition and decreased cellular response are associated with disseminated coccidioidomycosis.

Microtubules promote the non-cell autonomous action of microRNAs by inhibiting their cytoplasmic loading onto ARGONAUTE1 in Arabidopsis.

Mobile microRNAs (miRNAs) serve as local and long-distance signals in the developmental patterning and stress responses in plants. However, mechanisms governing the non-cell autonomous activities of miRNAs remain elusive. Here, we show that mutations that disrupt microtubule dynamics are specifically defective for the non-cell autonomous actions of mobile miRNAs, including miR165/6 that is produced in the endodermis and moves to the vasculature to pattern xylem cell fates in Arabidopsis roots. We show that KTN1, a subunit of a microtubule-severing enzyme, is required in source cells to inhibit the loading of miR165/6 into ARGONUATE1 (AGO1), which is cell autonomous, to enable the miRNA to exit the cell. Microtubule disruption enhances the association of miR165/6 with AGO1 in the cytoplasm. These findings suggest that although cell-autonomous miRNAs load onto AGO1 in the nucleus, the cytoplasmic AGO1 loading of mobile miRNAs is a key step regulated by microtubules to promote the range of miRNA cell-to-cell movement.

Lower extremity joint kinematics of a simulated lateral ankle sprain after drop landings in participants with chronic ankle instability.

This study examined lower extremity joint kinematics in individuals with chronic ankle instability (CAI) and controls during unanticipated and anticipated single-leg drop landings onto a laterally inclined platform. Physically active adults with CAI 15 (n = 15) and controls (n = 15) performed an unanticipated and anticipated 30 cm single-leg drop landing onto a 20° laterally inclined platform. Three-dimensional ankle, knee and hip-joint kinematics were recorded 200 ms pre- to 200 post-landing and analysed with a 2 (group) × 2 (landing condition) SPM ANOVA (p < 0.05). Results revealed individuals with CAI displayed significantly greater ankle internal rotation post-landing across both landing conditions. Anticipated landings elicited significantly greater pre-landing ankle inversion and external rotation, knee abduction and hip adduction. Additionally, significantly less ankle inversion, knee and hip flexion, and knee adduction and hip abduction were present during post-landing of the anticipated landing. Greater ankle internal rotation during landing may contribute to the ankle 'giving way' in individuals with CAI. However, preparatory and reactive proximal-joint kinematics were similar in both groups during landing. This highlights the possible role of the knee and hip joints in assisting with ankle-joint stability during anticipated inversion perturbations.

Ankle kinematics, center of pressure progression, and lower extremity muscle activity during a side-cutting task in participants with and without chronic ankle instability.

This study assessed ankle kinematics, surface electromyography, and center-of-pressure (COP) progression relative to the medial border of the foot during a side-cutting task in individuals with and without chronic ankle instability (CAI). Thirty participants (CAI = 15; Controls = 15) performed a side-cutting task on a force platform while 3-dimentional ankle kinematics, COP position, and surface electromyography from the tibialis anterior, medial gastrocnemius, fibularis longus, fibularis brevis, vastus medialis, and semitendinosus were recorded on the testing leg. Ankle kinematics, root-mean-square muscle activity and COP position relative to the medial boarder of the foot were compared between CAI and healthy controls (p < 0.05). Significantly greater ankle internal rotation from 35-54% of the stance phase (p = 0.032) was found for the CAI group compared to controls. Furthermore, significantly greater tibialis anterior muscle activity from 86-94% of the stance phase (p = 0.022) and a more medial COP position from 81-100% (p < 0.05) and of the stance phase was also observed in the CAI group. Less lateral COP progression and increased tibialis anterior activation in the CAI group could reflect a protective movement strategy during anticipated side-cutting to avoid recurrent injury. However, greater ankle internal rotation during mid-stance highlights a potential 'giving way' mechanism in individuals with CAI.

Genome-Wide Association Study for Maize Leaf Cuticular Conductance Identifies Candidate Genes Involved in the Regulation of Cuticle Development.

The cuticle, a hydrophobic layer of cutin and waxes synthesized by plant epidermal cells, is the major barrier to water loss when stomata are closed at night and under water-limited conditions. Elucidating the genetic architecture of natural variation for leaf cuticular conductance (gc) is important for identifying genes relevant to improving crop productivity in drought-prone environments. To this end, we conducted a genome-wide association study of gc of adult leaves in a maize inbred association panel that was evaluated in four environments (Maricopa, AZ, and San Diego, CA, in 2016 and 2017). Five genomic regions significantly associated with gc were resolved to seven plausible candidate genes (ISTL1, two SEC14 homologs, cyclase-associated protein, a CER7 homolog, GDSL lipase, and ß-D-XYLOSIDASE 4). These candidates are potentially involved in cuticle biosynthesis, trafficking and deposition of cuticle lipids, cutin polymerization, and cell wall modification. Laser microdissection RNA sequencing revealed that all these candidate genes, with the exception of the CER7 homolog, were expressed in the zone of the expanding adult maize leaf where cuticle maturation occurs. With direct application to genetic improvement, moderately high average predictive abilities were observed for whole-genome prediction of gc in locations (0.46 and 0.45) and across all environments (0.52). The findings of this study provide novel insights into the genetic control of gc and have the potential to help breeders more effectively develop drought-tolerant maize for target environments.

Lower Limb Joint Kinetics During a Side-Cutting Task in Participants With or Without Chronic Ankle Instability.

CONTEXT: Individuals with chronic ankle instability (CAI) demonstrate altered lower limb movement dynamics during jump landings, which can contribute to recurrent injury. However, the literature examining lower limb movement dynamics during a side-cutting task in individuals with CAI is limited. OBJECTIVE: To assess lower limb joint kinetics and sagittal-plane joint stiffness during the stance phase of a side-cutting task in individuals with or without CAI. DESIGN: Cohort study. SETTING: Motion-capture laboratory. PATIENTS OR OTHER PARTICIPANTS: Fifteen physically active, young adults with CAI (7 men, 8 women; age = 21.3 ± 1.6 years, height = 171.0 ± 11.2 cm, mass = 73.4 ± 15.2 kg) and 15 healthy matched controls (7 men, 8 women; age = 21.5 ± 1.5 years, height = 169.9 ± 10.6 cm, mass = 75.5 ± 13.0 kg). INTERVENTION(S): Lower limb 3-dimensional kinematic and ground reaction force data were recorded while participants completed 3 successful trials of a side-cutting task. Net internal joint moments, in addition to sagittal-plane ankle-, knee-, and hip-joint stiffness, were computed from 3-dimensional kinematic and ground reaction force data during the stance phase of the side-cutting task and analyzed. MAIN OUTCOME MEASURE(S): Data from each participant's stance phase were normalized to 100% from initial foot contact (0%) to toe-off (100%) to compute means, standard deviations, and Cohen d effect sizes for all dependent variables. RESULTS: The CAI group exhibited a reduced ankle-eversion moment (39%-81% of stance phase) and knee-abduction moment (52%-75% of stance phase) and a greater ankle plantar-flexion moment (3%-16% of stance phase) than the control group (P range = .009-.049). Sagittal-plane hip-joint stiffness was greater in the CAI than in the control group (t28 = 1.978, P = .03). CONCLUSIONS: Our findings suggest that altered ankle-joint kinetics and increased hip-joint stiffness were associated when individuals with CAI performed a side-cutting task. These lower limb kinetic changes may contribute to an increased risk of recurrent lateral ankle sprains in people with CAI. Clinicians and practitioners can use these findings to develop rehabilitation programs for improving maladaptive movement mechanics in individuals with CAI.

Effects of Weighted Vest Loading During Daily Living Activities on Countermovement Jump and Sprint Performance.

PURPOSE: Wearing a weighted vest (WV) during daily living and training can enhance jump and sprint performance; however, studies examining the efficacy of this method in female populations is limited. This study examined the effect of wearing a WV during daily living and training on countermovement jump (CMJ), change-of-direction, and sprint performance. METHODS: Trained females were separated into intervention (n = 9) and control (n = 10) groups. The intervention group wore WVs of ∼8% body mass 4 days per week for 8 hours per day (32 h/wk total), and 3 training sessions per week for the first 3 weeks. Subsequently, 3 weeks of regular training without WV stimulus was completed. The control group received no intervention and continued normal training for 6 weeks. Average and best performance was assessed on the single CMJ, four continuous CMJ, t-test change-of-direction drill, and a 25-m sprint at baseline, week 3, and week 6. RESULTS: No significant interactions or group effects were found. However, significant time main effects revealed increases in average rate of force development during the CMJ from baseline to week 3 (P = .048) and week 6 (P = .013), whereas peak vertical ground reaction force increased during the four continuous CMJ from baseline to week 3 (P = .048) and week 6 (P = .025) for both groups. CONCLUSIONS: The lower relative WV load used in this study failed to elicit significant improvements in jump and sprint performance in comparison with routine training, or that which have been found in past investigations with elite male athletes completing high-intensity performance tasks with greater WV loads.

Mean muscle activation comparison between fastballs and curveballs with respect to the upper and lower extremity.

Baseball research on muscle activity (upper and lower extremity) during the throwing motion is important to understanding pitching mechanics for the future. Therefore, it is the purpose of this research study to compare the lower extremity muscle and upper extremity muscle activation patterns associated with the curveball pitch and the fastball pitch from the stretch position. Twelve skilled (NCAA collegiate level) pitchers volunteered to be in this study, with a mean age of 22.3 ±â€¯4.53 years, mean height of 1.74 ±â€¯0.13 m, and mean mass of 89.0 k ±â€¯10.97 kg. The pitchers were fitted with six surface electromyography (EMG) bipolar electrodes on the stride leg biceps femoris, medial gastrocnemius, ipsilateral side lower trapezius, upper trapezius, triceps brachii and biceps brachii. Each pitcher underwent maximum voluntary isometric contraction (MVIC) testing and then performed the fastball & curveball pitching sequence. All EMG variables of interest were normalized using MVIC data and compared between pitching type. A repeated measures ANOVA was conducted for all muscle activity as well. If significance was found a pairwise analysis (Bonferroni) was performed between pitch type, using SPSS (p 0.05). Significant differences in the mean muscle activity for the fastball and curveball pitched from the stretch were observed. A higher level of muscle activity was found for the stretch fastball when compared to the stretch curveball. This study was able to provide a baseline measurement of muscle activity; however, kinematics and kinetics should be measured in future studies.

Bilateral spatiotemporal postural control impairments are present in participants with chronic ankle instability.

OBJECTIVES: This study evaluated center-of-pressure (COP) and time-to-boundary (TTB) measures of postural control during a Lateral Step-Down Test in participants with chronic ankle instability (CAI). DESIGN: Cohort study. SETTING: Biomechanics laboratory. PARTICIPANTS: Physically active adults with CAI (n = 15) and matched controls (n = 15). MAIN OUTCOME MEASURES: Traditional COP and TTB measures of postural control were computed in the medial/lateral (ML) and anterior/posterior (AP) directions. RESULTS: No significant results were found for the traditional COP measures (p > 0.05). The CAI group exhibited a lower TTB ML absolute minimum on their affected limb compared to the matched limb of the control group (p < 0.001). Additionally, on average the CAI group displayed significantly lower TTB ML mean of minima (p = 0.004) and TTB standard deviation of minima in the ML (p < 0.001) and AP directions (p = 0.002) regardless of limb. CONCLUSIONS: Sensorimotor impairments associated with CAI negatively alter spatiotemporal postural control and may cause a maladaptive reorganization of centrally mediated motor control strategies that results in bilateral postural control deficits during the Lateral Step-Down Test. In addition, traditional COP measures did not reveal any postural control deficits suggesting that a spatiotemporal analysis should be used when assessing postural control in participants with CAI.

Anticipating ankle inversion perturbations during a single-leg drop landing alters ankle joint and impact kinetics.

Anticipatory responses to inversion perturbations can prevent an accurate assessment of lateral ankle sprain mechanics when using injury simulations. Despite recent evidence of the anticipatory motor control strategies utilized during inversion perturbations, kinetic compensations during anticipated inversion perturbations are currently unknown. The purpose of this investigation was to examine the influence of anticipation to an inversion perturbation during a single-leg drop landing on ankle joint and impact kinetics. Fifteen young adults with no lateral ankle sprain history completed unanticipated and anticipated single-leg drop landings onto a 25° laterally inclined platform from a height of 30 cm. One-dimensional statistical parametric mapping (SPM) was used to analyze net ankle moments and ground reaction forces (GRF) during the first 150 ms post-landing, while peak GRFs, time to peak GRF, peak and average loading rates were compared using a dependent samples t-test (p ≤ 0.05). Results from the SPM analysis revealed significantly greater plantar flexion moment from 58 to 83 ms post-landing (p = 0.004; d = 0.64-0.77), inversion moment from 89 to 91 ms post-landing (p = 0.050; d = 0.58-0.60), and medial GRF from 62 to 97 ms post-landing (p < 0.001; d = 1.00-2.39) during the unanticipated landing condition. Moreover, significantly greater peak plantarflexion (p < 0.001; d = 1.10) and peak inversion moment (p = 0.007; d = 0.94), as well as greater peak (p = 0.002; d = 1.03) and average (p = 0.042; d = 0.66) medial loading rates, were found during the unanticipated landing condition. Our findings suggest alterations to ankle joint and impact kinetics occur during a single-leg drop landing when inversion perturbations are anticipated. Researchers and practitioners using drop-landings onto a tilted surface to assess lateral ankle sprain injury risk should consider implementing protocols that mitigate anticipatory responses.

Neuromuscular control in individuals with chronic ankle instability: A comparison of unexpected and expected ankle inversion perturbations during a single leg drop-landing.

While neuromuscular control deficits during inversion perturbations in chronic ankle instability (CAI) cohorts are well documented in the literature, anticipatory motor control strategies to inversion perturbations in CAI are largely unknown. The purpose of this study was to examine neuromuscular control and ankle kinematics in individuals with CAI (n = 15) and matched controls (n = 15) during unexpected and expected single leg drop-landings onto a tilted surface rotated 20° in the frontal plane. Muscle activity from 200 ms pre- to post-landing was recorded from the tibialis anterior (TA), medial gastrocnemius (MG), peroneus longus (PL) and peroneus brevis (PB). Mean muscle activity, co-contraction index (CCI), and peroneal latency was analyzed. Ankle inversion angle at initial contact, time to maximum inversion angle, maximum inversion angle and velocity were also assessed. Significantly longer PL latency, less time to maximum inversion and greater maximum inversion angle was found in CAI compared to controls. Regarding landing condition, significantly greater maximum inversion angle, less inversion at initial contact, longer PB latency, less TA activity and frontal plane CCI during the post-landing phase was found during the unexpected perturbation. Prolonged PL latency and altered ankle kinematics suggests reduced frontal plane ankle stabilization in CAI. However, similar motor control strategies were utilized in both groups during the ankle inversion perturbations.

Millimeter-Level Plant Disease Detection From Aerial Photographs via Deep Learning and Crowdsourced Data.

Computer vision models that can recognize plant diseases in the field would be valuable tools for disease management and resistance breeding. Generating enough data to train these models is difficult, however, since only trained experts can accurately identify symptoms. In this study, we describe and implement a two-step method for generating a large amount of high-quality training data with minimal expert input. First, experts located symptoms of northern leaf blight (NLB) in field images taken by unmanned aerial vehicles (UAVs), annotating them quickly at low resolution. Second, non-experts were asked to draw polygons around the identified diseased areas, producing high-resolution ground truths that were automatically screened based on agreement between multiple workers. We then used these crowdsourced data to train a convolutional neural network (CNN), feeding the output into a conditional random field (CRF) to segment images into lesion and non-lesion regions with accuracy of 0.9979 and F1 score of 0.7153. The CNN trained on crowdsourced data showed greatly improved spatial resolution compared to one trained on expert-generated data, despite using only one fifth as many expert annotations. The final model was able to accurately delineate lesions down to the millimeter level from UAV-collected images, the finest scale of aerial plant disease detection achieved to date. The two-step approach to generating training data is a promising method to streamline deep learning approaches for plant disease detection, and for complex plant phenotyping tasks in general.

Impact kinetics associated with four common bilateral plyometric exercises.

BACKGROUND: This study quantified the peak vertical ground reaction force (VGRF), impulse, and average and instantaneous loading rates developed during bilateral plyometric exercises. METHODS: Fourteen collegiate male athletes performed 4 different bilateral plyometric exercises within a single testing session. Depth jumps from thirty, 60 and 90 centimeter heights (DJ30, DJ60, and DJ90, respectively), and a 2 consecutive jump exercise (2CJ), were randomly performed. The subjects landed on and propelled themselves off two force platforms embedded into the floor. The stance phase of each plyometric movement was analyzed for vertical force characteristics. The dependent variables were normalized to body weight. One-way repeated-measures ANOVA revealed significant differences between exercises (P≤0.05). RESULTS: For VGRF, only the DJ60 and 2CJ exercises were not different from each other. The impulses between DJ60 and DJ90, and DJ30 and 2CJ, were not different. All exercises were different from each other in regards to average and instantaneous loading rate except for DJ30 vs. DJ60, and DJ90 vs. 2CJ. The DJ90 condition reported the highest peak VGRF by approaching five times body weight. The 2CJ condition had similar impulse and loading rates as the DJ90 condition. CONCLUSIONS: A proper progression and detailed program planning should be utilized when implementing plyometric exercises due to their different impact kinetics and how they might influence the body upon ground contact.

Lower-Extremity Kinematics During Ankle Inversion Perturbations: A Novel Experimental Protocol That Simulates an Unexpected Lateral Ankle Sprain Mechanism.

CONTEXT: Lateral ankle sprains are a common injury in which the mechanics of injury have been extensively studied. However, the anticipatory mechanisms to ankle inversion perturbations are not well understood. OBJECTIVE: To examine lower-extremity kinematics, including spatial and temporal variables of maximum inversion displacement and maximum inversion velocity, during landings on a tilted surface using a new experimental protocol to replicate a lateral ankle sprain. SETTING: Three-dimensional motion analysis laboratory. PARTICIPANTS: A total of 23 healthy adults. INTERVENTIONS: Participants completed unexpected (UE) and expected (EXP) unilateral landings onto a tilted surface rotated 25° in the frontal plane from a height of 30 cm. MAIN OUTCOME MEASURES: Ankle, knee, and hip kinematics at each discrete time point from 150 ms pre-initial contact (IC) to 150 ms post-IC, in addition to maximum ankle inversion and maximum inversion velocity, were compared between UE and EXP landings. RESULTS: The UE landing produced significantly greater maximum inversion displacement (P < .01) and maximum inversion velocity (P = .02) than the EXP landing. Significantly less ankle inversion and internal rotation were found during pre-IC, whereas during post-IC, significantly greater ankle inversion, ankle internal rotation, knee flexion, and knee abduction were observed for the UE landing (P < .05). In addition, significantly less hip flexion and hip adduction were observed for the UE landing during pre-IC and post-IC (P < .05). CONCLUSIONS: Differences in the UE and EXP landings indicate the experimental protocol presented a UE inversion perturbation that approximates the mechanism of a lateral ankle sprain. Furthermore, knowledge of the inversion perturbation elicited a hip-dominant strategy, which may be utilized to assist with ankle joint stabilization during landing to further protect the lateral ankle from injury.

Individuals with chronic ankle instability exhibit dynamic postural stability deficits and altered unilateral landing biomechanics: A systematic review.

OBJECTIVE: To evaluate the literature regarding unilateral landing biomechanics and dynamic postural stability in individuals with and without chronic ankle instability (CAI). METHODS: Four online databases (PubMed, ScienceDirect, Scopus, and SportDiscus) were searched from the earliest records to 31 January 2018, as well as reference sections of related journal articles, to complete the systematic search. Studies investigating the influence of CAI on unilateral landing biomechanics and dynamic postural stability were systematically reviewed and evaluated. RESULTS: Twenty articles met the criteria and were included in the systematic review. Individuals with CAI were found to have deficits in dynamic postural stability on the affected limb with medium to large effect sizes and altered lower extremity kinematics, most notably in the ankle and knee, with medium to large effect sizes. Additionally, greater loading rates and peak ground reaction forces, in addition to reductions in ankle muscle activity were also found in individuals with CAI during unilateral jump-landing tasks. CONCLUSIONS: Individuals with CAI demonstrate dynamic postural stability deficits, lower extremity kinematic alterations, and reduced neuromuscular control during unilateral jump-landings. These are likely factors that contribute recurrent lateral ankle sprain injuries during dynamic activity in individuals with CAI.

Coccidioidomycosis Complement Fixation Titer Trends in the Age of Antifungals.

Coccidioidomycosis is associated with a broad spectrum of illness severity, ranging from asymptomatic or self-limited pulmonary infection to life-threatening manifestations of disseminated disease. Serologic studies before the widespread availability of antifungals established current understanding of serologic kinetics and dynamics. Chart histories and complement fixation (CF) titer trends were analyzed for 434 antifungal-treated coccidioidomycosis patients, who were classified by three infectious disease physicians as having either pulmonary uncomplicated coccidioidomycosis (PUC) (n = 248), pulmonary chronic coccidioidomycosis (PCC) (n = 64), disseminated coccidioidomycosis (DC) not including meningitis (n = 86), or coccidioidal meningitis (CM) (n = 36). The median maximal CF titers were 1:4 for PUC patients, 1:24 for PCC patients, 1:128 for DC patients, and 1:32 for CM patients. Approximately 25.4% of PUC patients, 6.2% of PCC patients, 2.3% of DC patients, and 8.3% of CM patients did not develop detectable titers during the study period. Maximal titers developed a mean of 31 days (95% confidence interval [CI], 13 to 50 days) after initial serologic positivity, with no significant differences between groups. Serologic recurrence occurred in 9% of PUC patients, 36% of PCC patients, 50% of DC patients, and 52% of CM patients. Median titer improvement rates were 91 days/dilution for PUC patients, 112 days/dilution for PCC patients, 136 days/dilution for DC patients, and 146 days/dilution for CM patients. Receiver operating characteristic (ROC) analysis revealed that CF testing retains moderate classification value for disseminated infections (area under the curve [AUC], 0.82 [95% CI, 0.78 to 0.87]) and complicated infections (AUC, 0.82 [95% CI, 0.77 to 0.86]). A suitable cutoff value for complicated infections is ≥1:32. Findings update serologic parameters that are relevant for clinical assessment of coccidioidomycosis patients in the triazole era.

Image set for deep learning: field images of maize annotated with disease symptoms.

OBJECTIVES: Automated detection and quantification of plant diseases would enable more rapid gains in plant breeding and faster scouting of farmers' fields. However, it is difficult for a simple algorithm to distinguish between the target disease and other sources of dead plant tissue in a typical field, especially given the many variations in lighting and orientation. Training a machine learning algorithm to accurately detect a given disease from images taken in the field requires a massive amount of human-generated training data. DATA DESCRIPTION: This data set contains images of maize (Zea mays L.) leaves taken in three ways: by a hand-held camera, with a camera mounted on a boom, and with a camera mounted on a small unmanned aircraft system (sUAS, commonly known as a drone). Lesions of northern leaf blight (NLB), a common foliar disease of maize, were annotated in each image by one of two human experts. The three data sets together contain 18,222 images annotated with 105,705 NLB lesions, making this the largest publicly available image set annotated for a single plant disease.

Liposomal Amphotericin B as Monotherapy in Relapsed Coccidioidal Meningitis.

Coccidioidal meningitis remains a difficult clinical problem, and despite life-long therapy with triazole antifungals, relapses of disease and medication intolerance occur necessitating salvage treatment. We report two patients with recurrent coccidioidal meningitis who improved following a 2-week course of liposomal amphotericin B monotherapy and discuss potential advantages of this treatment option.