Search

Climate change is increasing the frequency and intensity of wildfires in many regions of the world. Changing fire regimes have been shown to delay vegetation recovery and shift distribution of ecosystems, increasing the importance of understanding the short-and long-term impacts of these changes. The unusually severe 2019–2020 Australian bushfire season has been linked to climate change and the impacts on wildlife and ecosystems are still being studied. We use remotely sensed thermal data to assess the differences between annual fire seasons from 2012 to 2019 in eastern Australia to understand the unique characteristics of the 2019–2020 anomalous fire season. We use spatial and temporal monitoring data of the vulnerable gray-headed flying fox (Pteropus poliocephalus) and its habitat to examine evidence for fire impacts on these important forest pollinators. We analyze roost occupancy in response to a previous fire season and use these results to identify roosts that are particularly affected by the 2019–2020 fires. During the 2019–2020 anomalous fire season, mega-fires, defined as contiguous fires over 10,000 hectares (ha) each, burned over 60% of the total affected area and occurred mostly in forested areas. This is in contrast to previous fire seasons in which smaller, scattered fires burned mostly non-forested areas. While we found little evidence that gray-headed flying fox reacted directly to fires in a previous season, unburned winter habitat was a key predictor of roost occupancy. The 2019–2020 anomalous fire season burned nearly ten times the amount of total habitat (33.7%) across the gray-headed flying fox range compared to the previous season. Critical winter habitats, including a species in fire refugia, were also substantially more burned in the anomalous fire season. Much of the winter habitat that burned in the anomalous fire season was within high or extreme severity fires (41.7%), causing substantial canopy consumption of these species. This work highlights the utility of remotely sensed thermal data for rapidly mapping fire impacts to wildlife and vegetation and highlights areas of habitat key for the conservation of these vulnerable populations.

While prey responses to predators reduce the threat of consumption, the physiological costs of these responses can be considerable. This is especially true for organisms that lack effective anti-predator defenses and must rely on camouflage or mimicry for protection. The luna moth, Actias luna, is a large saturniid native to Eastern North America that is preyed on and parasitized by a wide variety of predators and parasitoids. We report the results of two separate experiments assessing the responses of Actias larvae to predatory wasps (Vespula maculifrons) that were rendered non-lethal but remained able to move freely, as well as in a control (wasp-free) treatment. We determined whether these responses were predator-specific by also testing the response of Actias larvae to a similarly-sized but harmless scavenging fly. In both experiments, (A) Actias larvae in the wasp treatment died at a higher rate than those in the control treatments; and (B) larval survival in the fly and control treatments did not differ. Despite similar Actias survival in the fly and control treatments, fly-treatment larvae that died appeared to respond similarly to flies as other larvae did to wasps. In both years, larvae that died in the fly and wasp treatments gained virtually no weight between the start of the experiment and their death, suggesting that they may have succumbed to starvation. Our results, replicated over 2 years, illustrate the high cost of anti-predator responses and are the first report of lethal risk effects in caterpillars.

Background: Chronic hand eczema is a fluctuating, inflammatory, pruritic, often painful disease of hands and wrists that strongly impacts quality of life and occupational capabilities of patients. The aim of phase 3 DELTA 1 and DELTA 2 was to assess the efficacy and safety of twice-daily applications of the topical pan-Janus kinase inhibitor delgocitinib cream 20 mg/g versus cream vehicle in adults with moderate to severe chronic hand eczema., Methods: Both trials were randomised, double-blinded, and vehicle-controlled, with DELTA 1 being conducted at 53 trial centres in Canada, France, Germany, Italy, Poland, and the UK and DELTA 2 at 50 trial centres in Belgium, Canada, Denmark, Germany, the Netherlands, Poland, and Spain. Adults (aged ≥18 years) with moderate to severe chronic hand eczema were randomly assigned 2:1 to twice-daily delgocitinib cream 20 mg/g or cream vehicle for 16 weeks. The primary endpoint was Investigator's Global Assessment for Chronic Hand Eczema (IGA-CHE) treatment success at week 16, defined as IGA-CHE score of 0 (clear) or 1 (almost clear, defined as only barely perceptible erythema). Efficacy and safety were assessed in all patients who were exposed to trial treatment. These trials are registered with ClinicalTrials.gov, NCT04871711 and NCT04872101., Findings: Between May 10, 2021, and Oct 31, 2022, 487 patients (181 male and 306 female) were enrolled in DELTA 1; between May 25, 2021, and Jan 6, 2023, 473 patients (161 male and 312 female) were enrolled in DELTA 2. 325 patients in DELTA 1 and 314 in DELTA 2 were assigned to delgocitinib cream; 162 patients in DELTA 1 and 159 in DELTA 2 were assigned to cream vehicle. At week 16, a greater proportion of delgocitinib-treated patients versus cream vehicle patients had IGA-CHE treatment success (64 [20%] of 325 vs 16 [10%] of 162 in DELTA 1 and 91 [29%] of 313 vs 11 [7%] of 159 in DELTA 2; both trials p≤0·0055). The proportion of patients who reported adverse events was similar with delgocitinib (147 [45%] of 325 in DELTA 1 and 143 [46%] of 313 in DELTA 2) and the cream vehicle (82 [51%] of 162 in DELTA 1 and 71 [45%] of 159 in DELTA 2). Most frequent adverse events occurring in at least 2% of patients were similar in both treatment groups and included COVID-19 and nasopharyngitis., Interpretation: Overall, delgocitinib cream showed superior efficacy versus cream vehicle and was well tolerated over 16 weeks. These results support the clinical benefit of delgocitinib cream as a potential treatment option for patients with moderate to severe chronic hand eczema, who are unable to adequately control their disease with basic skin care practices and topical corticosteroids., Funding: LEO Pharma., Competing Interests: Declaration of interests RB is an advisory board member, consultant, speaker, or investigator for and receives honoraria or grants from AbbVie, Amgen, Apogee, Arcutis, Asana BioSciences, Bellus Health, BioMimetix, Bluefin Biomedicine, Boehringer Ingelheim, Boston, CARA Therapeutic, Clexio, Dermavant, Eli Lilly, Escient, Evidera, Fresh Tracks (Brickell), Galderma, GlaxoSmithKline, Incyte, Inmagene Bio, Janssen, LEO Pharma, Merck, Novartis, Opsidio, Pfizer, RAPT Therapeutic, Regeneron, Sanofi, Target RWE, Vyne Therapeutics, and Xencor. RB is also an employee and shareholder of Innovaderm Research. RBW has received research grants or consulting fees from AbbVie, Almirall, Amgen, Arena, Astellas, Avillion, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, DiCE, GSK, Janssen, Lilly, LEO Pharma, Novartis, Pfizer, Sanofi, Sun Pharma, UCB, and UNION. AP has served as an investigator, speaker, or advisor for AbbVie, Almirall-Hermal, Amgen, Biogen Idec, Biontec, Boehringer Ingelheim, BMS, Celgene, Celltrion, GSK, Eli Lilly, Galderma, Hexal, Janssen, LEO Pharma, MC2, Medac, Merck Serono, Mitsubishi, MSD, Novartis, Pascoe, Pfizer, Tigercat Pharma, Regeneron, Roche, Sandoz Biopharmaceuticals, Sanofi-Genzyme, Schering-Plough, UCB Pharma, and Zuellig Pharma. TA has given lectures, participated in clinical trials, or been on advisory boards for Sanofi, LEO Pharma, Pfizer, Eli Lilly, Galderma, and AbbVie. MG has been an investigator, speaker, or advisor for AbbVie, Acelyrin, Amgen, Akros, Arcutis, Aristea, AnaptysBio, Apogee, Bausch Health, BMS, Boehringer Ingelheim, Celgene, Dermira, Dermavant, Eli Lilly, Galderma, GSK, Incyte, InMagene, Janssen, Kyowa Kirin, LEO Pharma, MedImmune, Meiji, Merck, Moonlake, Nimbus, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Sun Pharma, Tarsus, Takeda, UCB, Union, and Ventyx. MLAS has been a consultant, advisory board member, investigator, or speaker for Sanofi Genzyme, Regeneron Pharmaceuticals, Pfizer, LEO Pharma, Eli Lilly, Galderma, AbbVie, Novartis, and Amgen. M-NC is a consultant, advisory board member, investigator, or speaker for AbbVie, Eli Lilly, LEO Pharma, Novartis, Pfizer, and Sanofi Genzyme. LS has been principal investigator in clinical trials sponsored by or has received personal fees for participation in advisory boards from AbbVie, Amgen, LEO Pharma, Eli Lilly, Novartis, and Sanofi, outside the submitted work. ES-B has served as an investigator or speaker or advisor for AbbVie, Almirall-Hermal, Lilly, LEO Pharma, Pfizer, Sanofi, Novartis, and Galderma. KB, MK, and UP are employees of LEO Pharma. SK and NSV were employees of LEO Pharma. SS is or has been a consultant, advisory board member, investigator, or speaker for LEO Pharma, Sanofi-Aventis, Novartis Pharma, Lilly Pharma, and AbbVie. All investigators had confidentiality agreements with the sponsor., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

The Investigator Global Assessment of Chronic Hand Eczema (IGA-CHE) is a novel Clinician-Reported Outcome measure that allows investigators to assess cross-sectional CHE global disease severity using clinical characteristics of erythema, scaling, lichenification/hyperkeratosis, vesiculation, oedema, and fissures as guidelines for overall severity assessment. This study aimed to evaluate the psychometric properties of the IGA-CHE for use as an outcome measure in CHE clinical trials and clinical practice. Psychometric analyses were performed using data from a sample of 280 patients with moderate to severe CHE from a phase 3 trial of delgocitinib cream, pooled across treatment groups. Test-retest reliability results were moderate to strong with kappa coefficients ranging from 0.63 to 0.76. Correlations with measures assessing related concepts were moderate or strong (range 0.65-0.72) and exceeded a priori hypotheses, providing evidence of convergent validity. Known-groups validity was supported by statistically significant differences between severity groups (< 0.001). Within-group effect sizes were consistently larger for improved groups compared to stable groups, providing evidence of ability to detect change. Anchor-based analyses generated within-subject meaningful change estimates ranging from - 0.8 to - 2.3. A correlation weighted average suggested a single value of - 1.7 in change from baseline. These findings provide evidence the IGA-CHE scale has strong reliability, construct validity, and ability to detect change, supporting its use as an endpoint in CHE clinical trials and clinical practice. Based on the evidence, 2-level changes in IGA-CHE score are considered a conservative meaningful change threshold; however, findings also indicate 1-level change in IGA-CHE scores reflects a clinically meaningful improvement for patients.Clinical trial registration: NCT04871711., (© 2024. The Author(s).)

Here, we present a protocol to generate B cell restricted mouse models of loss-of-function genetic drivers typical of lymphoproliferative disorders, using stem cell engineering of murine strains carrying B cell restricted Cas9 expression. We describe steps for preparing lentivirus expressing sgRNA-mCherry, isolating hematopoietic stem and progenitor cells, and in vitro transduction. We then detail the transplantation of engineered cells into recipient mice and verification of gene edits. These mouse models represent versatile platforms to model complex disease traits typical of lymphoproliferative disorders. For complete details on the use and execution of this protocol, please refer to ten Hacken et al., 1 ten Hacken et al., 2 and ten Hacken et al. 3 ., Competing Interests: Declaration of interests C.J.W. is an equity holder of BioNtech, Inc. and receives research funding from Pharmacyclics., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Pompe disease is a rare glycogen storage disorder caused by a deficiency in the lysosomal enzyme acid α -glucosidase, which leads to muscle weakness, cardiac and respiratory failure, and early mortality. Alglucosidase alfa, a recombinant human acid α -glucosidase, was the first approved treatment of Pompe disease, but its uptake into skeletal muscle via the cation-independent mannose-6-phosphate (M6P) receptor (CIMPR) is limited. Avalglucosidase alfa has received marketing authorization in several countries for infantile-onset and/or late-onset Pompe disease. This recently approved enzyme replacement therapy (ERT) was glycoengineered to maximize CIMPR binding through high-affinity interactions with ∼7 bis-M6P moieties. Recently, small molecules like the glucosylceramide synthase inhibitor miglustat were reported to increase the stability of recombinant human acid α -glucosidase, and it was suggested that an increased serum half-life would result in better glycogen clearance. Here, the effects of miglustat on alglucosidase alfa and avalglucosidase alfa stability, activity, and efficacy in Pompe mice were evaluated. Although miglustat increased the stability of both enzymes in fluorescent protein thermal shift assays and when incubated in neutral pH buffer over time, it reduced their enzymatic activity by ∼50%. Improvement in tissue glycogen clearance and transcriptional dysregulation in Pompe mice correlated with M6P levels but not with miglustat coadministration. These results further substantiate the crucial role of CIMPR binding in lysosomal targeting of ERTs. SIGNIFICANCE STATEMENT: This work describes important new insights into the treatment of Pompe disease using currently approved enzyme replacement therapies (ERTs) coadministered with miglustat. Although miglustat increased the stability of ERTs in vitro, there was no positive impact to glycogen clearance and transcriptional correction in Pompe mice. However, increasing mannose-6-phosphate levels resulted in increased cell uptake in vitro and increased glycogen clearance and transcriptional correction in Pompe mice, further underscoring the crucial role of cation-independent mannose-6-phosphate receptor-mediated lysosomal targeting for ERTs., (Copyright © 2023 by The Author(s).)

Transformation to aggressive disease histologies generates formidable clinical challenges across cancers, but biological insights remain few. We modeled the genetic heterogeneity of chronic lymphocytic leukemia (CLL) through multiplexed in vivo CRISPR-Cas9 B-cell editing of recurrent CLL loss-of-function drivers in mice and recapitulated the process of transformation from indolent CLL into large cell lymphoma [i.e., Richter syndrome (RS)]. Evolutionary trajectories of 64 mice carrying diverse combinatorial gene assortments revealed coselection of mutations in Trp53, Mga, and Chd2 and the dual impact of clonal Mga/Chd2 mutations on E2F/MYC and interferon signaling dysregulation. Comparative human and murine RS analyses demonstrated tonic PI3K signaling as a key feature of transformed disease, with constitutive activation of the AKT and S6 kinases, downmodulation of the PTEN phosphatase, and convergent activation of MYC/PI3K transcriptional programs underlying enhanced sensitivity to MYC/mTOR/PI3K inhibition. This robust experimental system presents a unique framework to study lymphoid biology and therapy., Significance: Mouse models reflective of the genetic complexity and heterogeneity of human tumors remain few, including those able to recapitulate transformation to aggressive disease histologies. Herein, we model CLL transformation into RS through multiplexed in vivo gene editing, providing key insight into the pathophysiology and therapeutic vulnerabilities of transformed disease. This article is highlighted in the In This Issue feature, p. 101., (© 2022 American Association for Cancer Research.)

The primary objective of this randomised, placebo-controlled, triple-blind study was to assess whether orally consumed Lactobacillus acidophilus La-14 (La-14) and Lacticaseibacillus rhamnosus HN001 (HN001) colonise a healthy human vagina. Furthermore, potential effects on vaginal microbiota and immune markers were explored. Fifty women devoid of vaginal complaints (Nugent score 0-3 and vaginal pH ≤ 4.5) were randomised into a 2-week intervention with either La-14 and HN001 as the verum product or a comparable placebo. Vaginal swab samples were collected at baseline, after one and two weeks of intervention, and after a one-week follow-up, for assessing colonisation of the supplemented lactobacilli, vaginal microbiota, and six specific immune markers. Colonisation of L. acidophilus and L. rhamnosus was not observed above the assay detection limit (5.29 and 5.11 log 10 genomes/swab for L. acidophilus and L. rhamnosus , respectively). Vaginal microbiotas remained stable and predominated by lactobacilli throughout the intervention, and vaginal pH remained optimal (at least 90% of participants in both groups had pH 4.0 or 4.5 throughout the study). Immune markers elafin and human β-defensin 3 (HBD-3) were significantly decreased in the verum group ( p = 0.022 and p = 0.028, respectively) but did not correlate with any microbiota changes. Adverse events raised no safety concerns, and no undesired changes in the vaginal microbiota or immune markers were detected.

Context: Environmental change impacts natural ecosystems and wildlife populations. In Australia, native forests have been heavily cleared and the local emergence of Hendra virus (HeV) has been linked to land-use change, winter habitat loss, and changing bat behavior., Objectives: We quantified changes in landscape factors for black flying foxes ( Pteropus alecto ), a reservoir host of HeV, in sub-tropical Queensland, Australia from 2000-2020. We hypothesized that native winter habitat loss and native remnant forest loss were greatest in areas with the most human population growth., Methods: We measured the spatiotemporal change in human population size and native 'remnant' woody vegetation extent. We assessed changes in the observed P. alecto population and native winter habitats in bioregions where P. alecto are observed roosting in winter. We assessed changes in the amount of remnant vegetation across bioregions and within 50 km foraging buffers around roosts., Results: Human populations in these bioregions grew by 1.18 M people, mostly within 50 km foraging areas around roosts. Remnant forest extent decreased overall, but regrowth was observed when policy restricted vegetation clearing. Winter habitats were continuously lost across all spatial scales. Observed roost counts of P. alecto declined., Conclusion: Native remnant forest loss and winter habitat loss were not directly linked to spatial human population growth. Rather, most remnant vegetation was cleared for indirect human use. We observed forest loss and regrowth in response to state land clearing policies. Expanded flying fox population surveys will help better understand how land-use change has impacted P. alecto distribution and Hendra virus spillover., Supplementary Information: The online version contains supplementary material available at 10.1007/s10980-023-01642-w., Competing Interests: Competing interestsThe authors declare no competing interests.Conflict of interestThe authors declare that they have no competing financial or non-financial interests that are directly or indirectly related to the work submitted for publication., (© The Author(s) 2023.)

Introduction: An analysis of samples originating from domestic and exotic animals from Lower Silesia but also from other parts of Poland was carried out based on research conducted in 2014-2017., Material and Methods: The materials used for the study were 11,338 tumour samples taken in vivo during surgery and as biopsies and posthumously during necropsies. They were sent to the Department of Pathology at Wrocław University of Environmental and Life Sciences for histopathological diagnosis., Results: The largest group were canine tumours, of which there were 9,745 (85.95%), followed by feline tumours, totalling 1,397 (12.32%), tumours from exotic animals (186; 1.64%), from horses (7; 0.06%), and from cows (2; 0.02%). A significant number of cases of animals suffering from more than one tumour were also found, which had not been frequently diagnosed previously., Conclusion: The number of neoplasms diagnosed in pets and exotic animals is increasing every year. The average animal age at diagnosis continues to fall. The greatest number of neoplasms were diagnosed in mixed-breed dogs and cats, and the number of tumours in a pure breed strictly correlated with breed's popularity in the research period. Mesenchymal tumours are still the most prevalent type of tumours in dogs, while in cats epithelial tumours predominate. The neoplasm case pattern in animals conforms to that in humans in the same area., Competing Interests: Conflict of Interest Conflict of Interests Statement: The authors declare that there is no conflict of interests regarding the publication of this article., (© 2022 R. Ciaputa et al. published by Sciendo.)

Acute upper respiratory tract infections (URTIs) are caused by numerous viruses and bacteria. URTIs can be a cause of morbidity and are among the most common reasons for visiting healthcare practitioners and prescribing antibiotics to children in addition to causing absenteeism from school and work. Oral intake of Lacticaseibacillus rhamnosus GG DSM 33156 has shown beneficial health effects in several clinical trials, primarily relating to immune function and gastrointestinal health in children and adults. It has also been suggested that oral intake of L. rhamnosus GG DSM 33156 can reduce the incidence rate and alleviate symptoms of URTIs in children. We here report the results of a randomised, double-blind, placebo-controlled trial of 619 children aged 2-6 years conducted at a single centre in Scotland. The children, who were in day care or primary school, were followed over a 16-week intervention period with 309 randomised in the active group and 310 in the placebo group. The parents or guardians reported a daily healthcare status and any presumed episodes of URTI, which were subsequently confirmed by a general practitioner. The investigational product was well tolerated in the trial. Although a general trend towards a beneficial effect was observed, this trial did not demonstrate that L. rhamnosus GG DSM 33156 significantly reduced the incidence of URTIs, diagnosed by a general practitioner according to prespecified criteria (primary endpoint). Moreover, none of the secondary efficacy endpoints were met. Applying a Ward's hierarchical clustering, two separate clusters, focussing on four quality of life-related endpoints, were identified. Cluster 1 was associated with more severe URTI characteristics than cluster 2. Cluster 2 was significantly enriched with children who consumed the product, indicating that the symptoms children experience during an URTI are alleviated by the intake of L. rhamnosus GG DSM 33156. The study is registered at ClinicalTrials.gov ID: NCT03636191.

CRISPR-Cas9 gene editing has transformed our ability to rapidly interrogate the functional impact of somatic mutations in human cancers. Droplet-based technology enables the analysis of Cas9-introduced gene edits in thousands of single cells. Using this technology, we analyze Ba/F3 cells engineered to express single or multiplexed loss-of-function mutations recurrent in chronic lymphocytic leukemia. Our approach reliably quantifies mutational co-occurrences, zygosity status, and the occurrence of Cas9 edits at single-cell resolution.

Mitochondrial apoptosis can be effectively targeted in lymphoid malignancies with the FDA-approved B cell lymphoma 2 (BCL-2) inhibitor venetoclax, but resistance to this agent is emerging. We show that venetoclax resistance in chronic lymphocytic leukemia is associated with complex clonal shifts. To identify determinants of resistance, we conducted parallel genome-scale screens of the BCL-2-driven OCI-Ly1 lymphoma cell line after venetoclax exposure along with integrated expression profiling and functional characterization of drug-resistant and engineered cell lines. We identified regulators of lymphoid transcription and cellular energy metabolism as drivers of venetoclax resistance in addition to the known involvement by BCL-2 family members, which were confirmed in patient samples. Our data support the implementation of combinatorial therapy with metabolic modulators to address venetoclax resistance., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Convolutional neural network (CNN) models have the potential to improve plant disease phenotyping where the standard approach is visual diagnostics requiring specialized training. In scenarios where a CNN is deployed on mobile devices, models are presented with new challenges due to lighting and orientation. It is essential for model assessment to be conducted in real world conditions if such models are to be reliably integrated with computer vision products for plant disease phenotyping. We train a CNN object detection model to identify foliar symptoms of diseases in cassava ( Manihot esculenta Crantz). We then deploy the model in a mobile app and test its performance on mobile images and video of 720 diseased leaflets in an agricultural field in Tanzania. Within each disease category we test two levels of severity of symptoms-mild and pronounced, to assess the model performance for early detection of symptoms. In both severities we see a decrease in performance for real world images and video as measured with the F-1 score. The F-1 score dropped by 32% for pronounced symptoms in real world images (the closest data to the training data) due to a decrease in model recall. If the potential of mobile CNN models are to be realized our data suggest it is crucial to consider tuning recall in order to achieve the desired performance in real world settings. In addition, the varied performance related to different input data (image or video) is an important consideration for design in real world applications.

Introduction: It has been demonstrated that plasma growth factor (PGF) responsible for proliferation of smooth muscle cells and fibroblasts significantly shortens treatment duration., Aim: To determine the role of human growth factor in the healing of ulcers due to ischaemic diabetic foot syndrome (DFS) following previous angioplasty of the blood vessels of the lower leg and foot., Material and Methods: The study group included 50 patients with ischaemic diabetic foot complicated by lower leg ulcers in which angioplasty of the stenotic arteries in the distal lower leg and foot was performed. It has been assumed that the area of the ulcer cannot exceed 5 cm 2 . Following surgical debridement, each patient received platelet-rich plasma in the form of dressings applied on an ulcer, followed by hydrocolloid dressings. Each dressing was replaced after 10 days, and this procedure was repeated after 20 and 30 days of treatment. The control group included 50 patients with ischaemic diabetic foot complicated by an ulcer up to 5 cm 2 . Angioplasty of the lower leg arteries was also performed in this group. However, after surgical debridement, wounds were covered with hydrocolloid dressings., Results: After 3 months of combined treatment, all wounds in the study group healed whereas in the control group, only wounds of the smallest size healed., Conclusions: Combined treatment of ulcers due to ischaemic DFS with endovascular procedures to re-establish blood flow to the vessels and dressings with autologous platelet-rich plasma significantly shortens the healing time.

Cassava is the third largest source of carbohydrates for human food in the world but is vulnerable to virus diseases, which threaten to destabilize food security in sub-Saharan Africa. Novel methods of cassava disease detection are needed to support improved control which will prevent this crisis. Image recognition offers both a cost effective and scalable technology for disease detection. New deep learning models offer an avenue for this technology to be easily deployed on mobile devices. Using a dataset of cassava disease images taken in the field in Tanzania, we applied transfer learning to train a deep convolutional neural network to identify three diseases and two types of pest damage (or lack thereof). The best trained model accuracies were 98% for brown leaf spot (BLS), 96% for red mite damage (RMD), 95% for green mite damage (GMD), 98% for cassava brown streak disease (CBSD), and 96% for cassava mosaic disease (CMD). The best model achieved an overall accuracy of 93% for data not used in the training process. Our results show that the transfer learning approach for image recognition of field images offers a fast, affordable, and easily deployable strategy for digital plant disease detection.

One of the complications of pancreatic disease is the formation of pancreatic fistulae. The presence of fistula leads to body wasting and cachexia. The standard treatment is intubation of the Wirsung duct and in cases where there are no improvements the next proposed form of treatment is surgery. The aim of the study was to evaluate the efficacy of pancreatic fistula closure using interventional radiology techniques. In 2009 to 2014, 46 patients diagnosed with pancreatic fistula were treated with interventional radiology techniques. Treatment consisted of vascular coil implanted at the entry of the fistula and then sealed with tissue glue adhesive during endoscopic procedure. Technical success of vascular coil implantation and the use of tissue glue adhesive were reported in all patients. Pancreatic fistula recurred in 7 patients (15.2%). The latter group of patients underwent statistical analysis to determine what the risk factors in recurring pancreatic fistulas were. The results indicate a significant relationship between etiology of the fistula and treatment effect., In Conclusion: (1) the use of interventional radiology methods in the closure of pancreatic fistula is an effective and safe procedure; and (2) the recurrence of fistula is dependent on the etiology and often occurs after surgery or trauma.

The ability to fluorescently label microtubules in live cells has enabled numerous studies of motile and mitotic processes. Such studies are particularly useful in budding yeast owing to the ease with which they can be genetically manipulated and imaged by live cell fluorescence microscopy. Because of problems associated with fusing genes encoding fluorescent proteins (FPs) to the native α-tubulin (TUB1) gene, the FP-Tub1 fusion is generally integrated into the genome such that the endogenous TUB1 locus is left intact. Although such modifications have no apparent consequences on cell viability, it is unknown if these genome-integrated FP-tubulin fusions negatively affect microtubule functions. Thus, a simple, economical and highly sensitive assay of microtubule function is required. Furthermore, the current plasmids available for generation of FP-Tub1 fusions have not kept pace with the development of improved FPs. Here, we have developed a simple and sensitive assay of microtubule function that is sufficient to identify microtubule defects that were not apparent by fluorescence microscopy or cell growth assays. Using results obtained from this assay, we have engineered a new family of 30 FP-Tub1 plasmids that use various improved FPs and numerous selectable markers that upon genome integration have no apparent defect on microtubule function., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction/Background. Nonmetastatic castrate resistant prostate cancer (CRPC) is a challenging disease state. The objective of this study was to evaluate the efficacy and tolerability of bevacizumab in nonmetastatic CRPC patients. Patients. Patients with prostate cancer who developed PSA recurrence after local therapy were included if they had absence of bone or visceral metastases and PSA progression despite androgen deprivation therapy. Methods. Bevacizumab 10 mg/kg intravenously was administered every 14 days until PSA progression, development of metastasis, or unacceptable toxicity. Results. 15 patients were enrolled and treated with bevacizumab for a median duration of 3.1 months. Median baseline PSA was 27 ng/mL, and seven patients had Gleason Score ≥8. Five patients had declined in PSA during the treatment. Median PSA doubling time was prolonged from 4.7 months pretreatment to 6.5 months. Median time to PSA progression and new metastasis were 2.8 and 7.9 months, respectively. There were three grade 3 adverse events (one proteinuria and two hypertension) and one pulmonary embolism. There was no treatment-related mortality. Conclusion. Bevacizumab therapy had minimal impact on the disease course of nonmetastatic CRPC, and investigation of novel strategies is needed.

Background: Food in its composition contains anti-nutritional substances that reduces or prevents the use of valuable nutrients. The oxalic acid, as phytate and dietary fiber, occurs naturally in foods of plant origin, to which the beer is classified. The negative effect of oxalic acid is reducing the bioavailability of calcium and magnesium, and disorder of metabolism of the body's absorption of these elements from the diet. The excess of oxalic acid and its salt in the diet contributes to the formation of certain diseases, such as oxalate urolithiasis, osteoporosis, arthritis, etc. Due to the diuretic effect of beer, drinking moderate amounts of it is recommended as a preventive and support urinary tract disorders., Objective: The aim of this study was to determine and comparison the oxalic acid content in selected beers available on the Polish market., Material and Method: Fifty seven samples of beer were used for this study. These samples were divided into three groups depending on the alcohol concentration declared by the producers (1st group--below 5.5% vol., 2nd group--from 5.5 to 6.5% vol., 3rd group--above 6.5% vol.). The beer samples were incubated in the ultrasonic bath for 15 minutes following pH adjustments up to pH = 2 with the 1 mol/L hydrochloric acid to transform calcium oxalates into soluble form, then filtered. The oxalic acid concentration was measured by high performance liquid chromatography (HPLC) with conductivity detection., Results: The concentration of oxalic acid in tested samples of beer ranged from 1.8 to 30.3 mg/L. No considerable differences between the concentration of oxalic acid in the three tested group of beer with the various content of the alcohol were found. Basing on the average concentrations of the oxalic acid in the different groups of the tested beers the positive trend in oxalic acid concentration related to the increase of alcohol could be observed., Conclusions: The very low concentration of oxalic acid allows to classify beer as food product safe for the human health in terms of low oxalates content.

Objectives: To evaluate the toxicity and efficacy of capecitabine and weekly docetaxel in a phase II clinical trial., Methods: Eligibility included metastatic renal cancer with a maximum of 2 prior regimens, performance status of 0-2, and adequate renal, hepatic, and bone marrow function. Docetaxel was administered intravenously at a dose of 36 mg/m(2) weekly on days 1, 8, and 15 of a 28- day cycle and capecitabine was administered orally at a dose of 1800 mg/m(2) from days 5-18. Toxicity was assessed on days 1, 8, and 15 of each cycle, and response was evaluated every 2 cycles., Results: Twenty-five patients, 19 white and 6 African American, were enrolled on this phase II trial. The median age was 60 years (range: 39-75 years). Eighteen patients had clear cell histology, 7 had papillary, sarcomatoid, or chromophobe histology. Thirteen had liver/bone metastases and 13 had >or=2 of the Memorial Sloan-Kettering Cancer Center prognostic risk factors. Twelve patients received prior immunotherapy. A total of 93 cycles were administered; median of 3 cycles and range from 0-10 cycles. The therapy was well tolerated. No treatment-related mortality was observed and 2 treatment-related hospitalizations for nausea, diarrhea, and dehydration occurred. Ten patients had stable disease. The median time to progression was 1.7 months and median survival was 11.1 months., Conclusions: The combination of capecitabine and docetaxel was well tolerated in metastatic renal cancer. Clinical activity was predominantly noted in non-clear cell histology in which chemotherapy would be worthy of future investigation.

Objectives: To evaluate the toxicity and efficacy of interferon and thalidomide combination in a phase II clinical trial., Patients and Methods: Eligibility included metastatic renal cancer with a maximum of two prior regimens, performance status of 0-2 and adequate renal, hepatic and bone marrow function., Results: Twenty patients were enrolled on this phase II trial. Median age was 60.5 years (Range: 39-75 years). 17 patients had visceral metastases (lung/liver/both) and 3 patients had lymph node only metastases. A total of 26 cycles of 4 weeks each were administered; median of 1 cycle and range from 0-9 cycles. The therapy was poorly tolerated with grade 3 adverse events noted in 12 (60%) of the 20 patients. No objective responses were noted. Of the 14 response evaluable patients, one had an unconfirmed response (38% decrease in size) and one had prolonged disease stabilization for 10 months. The median time to progression was 1.0 month and median survival was 2.8 months. Pre and post therapy PET scans were performed nine weeks apart on one patient. The mean standardized uptake values (SUV) declined from 1.45 (SUV min-max 0.89-1.76) to 1.12 (SUV min-max 0.55-1.47), denoting anti vascular effect. The patient did not have an objective response but had a disease stabilization sustained for 10 months., Conclusion: The combination of interferon and thalidomide has minimal efficacy and considerable toxicity which makes this combination unworthy of future investigation in metastatic renal cancer.

Purpose/objectives: To explore the experiences of couples living with prostate cancer, the impact of the illness on their quality of life, their ability to manage symptoms, and their suggestions for interventions that would help them to improve their daily experiences., Design: Descriptive, qualitative., Setting: Six focus groups were used to obtain the data; two were patient-only groups, two were spouse-caregiver groups, and two were dyad groups. The focus groups were conducted at two comprehensive cancer centers in the midwestern region of the United States., Sample: 42 participants: 22 men with prostate cancer and 20 spouse-caregivers., Methods: Focus group discussions were tape-recorded, and the content was analyzed., Main Research Variables: Quality of life, symptom experience, and areas for intervention., Findings: Four major themes emerged from the data: enduring uncertainty, living with treatment effects, coping with changes, and needing help., Conclusions: Participants had a need for information and support. Both men and spouse-caregivers felt unprepared to manage treatment effects. Symptoms had a broad effect on couples, not just men. Positive effects of the illness, as well as negative effects, emerged from the themes., Implications for Nursing: Attention needs to be given to methods of providing information and support to couples coping with prostate cancer. Both patients and partners need to be included in discussions about the effect of the illness and treatments so that both can feel more prepared to manage them.

The axonal transport, metabolism, and transcellular transfer of uridine, adenosine, putrescine, and spermidine have been examined in intact and regenerating optic nerves of goldfish. Following intraocular injection of labeled nucleosides, axonal transport was determined by comparing left-right differences in tectal radioactivity, and transcellular transfer was indicated by light autoradiographic analysis. The results demonstrated axonal transport, transcellular transfer, and periaxonal cell utilization of both nucleosides in intact axons and severalfold increases of all of these processes in regenerating axons. Experiments in which the metabolism of the nucleosides was studied resulted in data which suggested that uridine and adenosine, when delivered to the tectum by axonal transport, are protected from degradation and thus are relatively more available for periaxonal cell utilization than nucleosides reaching these cells via the blood. In intact axons, the majority of the nonmetabolized radioactivity was present as UMP, UDP, and UTP following [3H]uridine injections, whereas the majority of the radioactivity following [3H]adenosine injections was present as adenosine, with the phosphorylated derivatives constituting a smaller proportion. During nerve regeneration, the relative proportion of nucleosides to nucleotides was reversed, with uridine being the principal labeled compound in the first case, and AMP, ADP, and ATP being the major labeled compounds in the latter case. The nucleosides also were found to be different from each other in that adenosine, but not uridine, can be taken up by optic axons and transported retrogradely from the tectum to retinal ganglion cell bodies in the eye. Following intraocular injection of [3H]spermidine, radioactivity was transported to the optic tectum and transferred to tectal cells in the vicinity of the regenerating axons. Following [3H]putrescine injections, silver grains were found over periaxonal glia, but preliminary findings suggest that they are not present over tectal neurons nor over radial glial cells in the periependymal layers. Analysis of tectal radioactivity showed in each case that it was composed primarily of the injected compounds. These studies indicate that, following axonal transport, the polyamines do not remain within regenerating axons but are transferred to cells surrounding the axon. On the basis of these and previous findings, we speculate that the axonal transport and transcellular transfer of uridine, adenosine, polyamines, and perhaps other small molecules are means of communication between axons and periaxonal cells; that the axon can affect RNA and protein synthesis in periaxonal cells by regulating the availability of these small molecules; and that, during nerve regeneration, the increased metabolic needs of periaxonal cells are met by an increased axonal supply of precursors (adenosine and uridine) and other molecules (polyamines) critical for protein synthesis.

Zygosaccharomyces bailii possesses a constitutive malic enzyme, but only small amounts of malate are decomposed when the cells ferment fructose. Cells growing anaerobically on glucose (glucose cells) decompose malate, whereas fructose cells do not. Only glucose cells show an increase in the intracellular concentration of malate when suspended in a malate-containing solution. The transport system for malate is induced by glucose, but it is repressed by fructose. The synthesis of this transport system is inhibited by cycloheximide. Of the two enantiomers L-malate is transported preferentially. The transport of malate by induced cells is not only inhibited by addition of fructose but also inactivated. This inactivation is independent of the presence of cycloheximide. The transport of malate is inhibited by uranyl ions; various other inhibitors of transport and phosphorylation were of little influence. It is assumed that the inducible protein carrier for malate operates by facilitated diffusion. Fructose cells of Z. bailii and cells of Saccharomyces cerevisiae do not contain a transport system for malate.