bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthetic Pyrethroid Insecticide Efficacy Trial, 1979
Authors: Smilowitz Zane , Dripps James E. , Yocum John O. , Martinka Carol A
Published: March 2022

A randomized complete block design with 3 replications was used at the Southeastern Field Research Laboratory in Lancaster County, PA. Plots consisted of four 20 ft rows, each plot separated by a 5 ft alleyway. Row spacing was 34 inches and seed tubers were set 9 inches apart within rows. Certified, Class B ‘Katahdin’ seed tubers were planted Jun 7. Temi k 15G was applied in furrow at planting at 3.0 lb ai/acre. Dithane M-45 was applied at 1.5 lb ai/acre on a 5-7 day schedule for potato late blight control. The foliar insecticides were applied on Aug 9 and Sep 7 with a Meyers air blast sprayer in 50 gal of water per acre at 200 psi. Ten stems per plot were sampled weekly for all stages of Colorado potato beetle (CPB) beginning on Jul 3. Green peach aphid (MyzuspersicaeSulz.) populations were limited by an early season application of Pirimor 50WP. Two rows per plot were harvested on Oct 2b and graded by size. Precipitation totalled 2.67 inches in Jun, 5.43 inches in Jul, 3.39 inches in Aug, and 5.96 inches in Sep. Average maximum and minimum temperatures (0F) were 79.0 and 55.5 for Jun, 83.2 and 60.8 for Jul, 82.5 and 60.7 for Aug and 76.9 and 52.5 for Sep. Approximately 1.71 inches of rain fell within 3 days after the Aug 9 application which may have reduced efficacy. CPB severity was light to moderate. Insecticide application was delayed until an acceptable infestation had developed in the plots.
Control of Spotted Alfalfa Aphid on Alfalfa, 1978
Authors: Berg G.N. , Ridland P.M. , East R.W.
Published: March 2022

Seven insecticides were tested on irrigated alfalfa at Goorambat, Victoria, Australia. Treatments consisted of 5 x 10 m plots, replicated 4 times in a randomized complete block design. A 2.5 m wide unsprayed buffer separated each plot. Applications were made with a Drake and FLetcher mistifier at a rate equivalent to 200 1 of water per ha at 40 psi with flat fan nozzles. Treatments were applied on Feb 7 when the lucerne was 30 cm high. Except for day +8, counts were made in the field by recording the number of aphids and other insects on 5 stems selected at random within each plot. The day +8 samples were made by bulking 5 stems from each plot and removing the aphids from the stems in the laboratory using hot water (80°C).
Apple, Concentrate Airblast Insecticide Test, 1982
Authors: Hull Larry A. , Beers Elizabeth H. , Meagher Robert L.
Published: March 2022

Sprays were applied to single-tree plots in a randomized block design consisting of 2 replicates of York Imperial and 4 replicates of Golden Delicious. Treatments were applied with an airblast sprayer at 25 gpa/alternate side spray driven at 2 mph. Rates for treatments are listed as amounts/acre/both sides spray. Spray dates for treatments were: May 20 and 27; Jun 4, 14, 21 and 28; Jul 6, 15 and 26; Aug 3, 11, 20 and 27; and Sept 3. Fungicides applied during the season were: Cyprex, Polyram, sulfur, oaptan, zineb and calcium chloride. Average temperatures were: May 66UF, Jun 67°F, Jul 78°F, Aug 74°F and Sept 63°F. Rainfall in inches totaled: May 2.45, Jun 6.65, Jul 3.00, Aug 1.80 and Sept 2.65. Effectiveness on apple aphid was evaluated by counting aphid infested leaves/10 top terminals, and aphids/most infested leaf/infested terminal. Effect of the sprays on white apple leafhopper was evaluated by counting nymphs/25 leaves/tree. Effectiveness of test chemicals on European red mite and two-spotted spider mite was evaluated by counting mites several times during the season on samples of 15 leaves/tree, 90 leaves/treatment. Effects of sprays on the predator S. punctum were evaluated by 3-minute counts of adults and larvae around the periphery of the test trees. Effectiveness of chemicals on fruit feeders was assessed by scoring for injury all drops after Jul 1, and 2 pick samples on Aug 17 and Sept 21. Apple samples averaged 137 fruits/replicate and 822/treatment.
Control of Tobacco Flea Beetles and Apterous Green Peach Aphid on Burley Tobacco, 1982
Authors: Jones G.A. , Smith E.T.
Published: March 2022

Burley tobacco was transplanted May 25 it South Farm, Lexington, in Maury silt loam soil. Prior to spraying, plots were laid out in single 25 ft by 3.5 ft rows with an jntreated row adjacent to each treated row. Rows were spaced 42 in apart with 18 in between plants. Fifteen foliar insecticides and 1 fungicide were tested in a randomized block design replicated 3 times. Maleic hydrazide at a rate of 3.75 lb ai/acre was :ank mixed with all insecticide and fungicide treatments. Pesticides were applied Aug 4 with a CO2-backpack sprayer equipped with TX12 nozzles operating at 30 psi and delivering 30 gpa. Live flea beetle counts and apterous aphid ratings were taken from 5 plants in each replication 2 and 8 days after application to measure efficacy and longevity of the insecticides.
Efficacy of 0Rgan0Flu0Rine Compounds Against the Red Imported Fire Ant, 1980
Authors: VanderMeer Robert K. , Williams David F. , Lofgren Clifford S.
Published: March 2022

Twenty worker ants from laboratory colonies of the red imported fire ant (RIFA) starved for 14 days were placed in 30-ml disposable plastic cups modified to provide a humid environment. Candidate chemicals were dissolved in once refined soybean oil (SBO) and presented to the ants on a cotton swab placed in a vial cap that was then placed in 1 of the cups. The ants were allowed to feed on the treated SBO for 24 h, after which, the treated cotton swabs were removed. After another 24 h fresh vial caps with untreatd SBO saturated cotton swabs were made available to the ants for the duration of the test. Mortality counts were made at intervals of 1, 2, 3, 6, 8, 10 and 14 days after initial exposure. Each test consisted of 3 replications at 3 concentrations, 1.0, 0.1 and 0.01%. Room temperature was maintained at 26.7 ± 2.2°C. A SBO control and a mi rex standard were used in all tests. Based on encouraging USDA screening results for 3 fluon’nated alcohols (AI3-23780-23782) from several years ago, we tested 28 commercially available fluorinated compounds. Four compounds showed significant delayed toxicity at 1.0%; however, these compounds did not have activity at lower concentrations. Although none of the compounds tested appeared to be suitable fire ant toxicants, the results were encouraging and our laboratory is investigating other organofluorine compounds for toxicity against these ants.
Pear, Pest Control, 1982
Authors: Burts Everett
Published: March 2022

Eighteen-year-old pear trees were sprayed with handguns operating at 600 psi to evaluate pesticides for control of pear pests. Plots consisted of five 2-tree replications in randomized block design. Treatments were evaluated for pear psylla control by counts of adults and nymphs at 2-wk intervals. Adults were counted by taking 5 beating-tray samples/rep. Nymphs were counted from 50-leaf samples/rep. The proximal, distal and 3 leaves from between were collected from each of 10 randomly-selected shoots. Phytophagous mites were counted from 50-leaf samples selected at random from each rep. All leaf samples were brushed and 20% of the resulting discs were examined with a dissecting microscope. Two harvest samples of 10 fruits/rep were weighed, tested for firmness with a penetrometer and rated for pear psylla honeydew russet and pear rust mite russet according to U.S. grade standards. Soluble solids were measured with a refractometer on samples of the combined juice of each lot of 10 fruit. Fruit and foliage were examined for phytotoxicity after each spray date. Pear psylla density was low in the block throughout the season so that test materials were not subjected to a severe test.
Broad Mite Pesticide Efficacy Test in California, 198
Authors: Jones V. P. , Morse J. G. , Yost J. T.
Published: March 2022

Acaracides were tested for control of broad mite populations on 8-year-old lemon trees located in Fallbrook, Ca. The experiment consisted of 4 single tree replicates per treatment. Treatments were applied Sep 20 with a Hardie handgun (single nozzle, #8 disc) at 450 psi (ca. 1200 gpa) until runoff using a John Bean sprayer. The trees were sampled by taking 10 fruit per tree and examining one field's width of a 14x handlens down the interior facing side of the fruit parallel to the stem. An index of infestation (where 0 mites = 0, 1-2 mites = 1, 3-5 mites = 2, 6-9 mites = 3, 10-14 mites = 4, 15-20 mites = 5, and 21+ mites = 6) was calculated for each fruit and averaged for the 10 fruit per tree. The mean index per tree was then subjected to ANOVA with Duncan's NMRT being used to separate treatment means at p = 0.05. Maximum index per treatment was 6.
Candidate Pesticides for Quarantine Use, 1982
Authors: Morgan Neal O. , Morgan Neal O. , Witherell Peter C.
Published: March 2022

Laboratory reared species were caged and exposed to pesticide formulations intransport trailers (ca 74 m volume) in Miami, Florida. One hundred each adult house flies and mosquitoes, 50 adult Germancockroaches and 30 adult boll weevils were caged in 0.24 1 paper cans. All cages were covered on the upper surface with 6 × 7mesh/cm2 nylon net. Cages of test insects were placed on the floor of each trailer near the center and close to a side. Aerosolswere formulated with R-12 propellant. Aerosols were released inside closed trailers while the applicator walked the length of the trailer. Manual release aerosols were sprayed for the required length of time based on release rate, and an accurate dose wasobtained by weighing and releasing additional material as necessary. Dusts were formulated with HiSi1 233 as an inert carrierand were introduced into the trailers with a CO2 'gun'. Dusts were administered through an open rear door. Exposure lasted for10 min with doors closed and an additional 20 miri with one door open. Knockdown counts were made at 30 min and mortality (dead +moribund) counts were made at 24 h post-treatment. Average temp at treatment was 26 C. Tests were replicated 3 times.
An Amidinohydrazone Bait (Combat: Maxforce) Against Cockroach Pest Species, 1982
Authors: Appel A. G. , Reierson D. A. , Rust M. K.
Published: March 2022

The acceptance and toxicity of amidinohydrazone (American Cyanamid CL217.300) bait (1.65% ai) was evaluated in the laboratory against 9 cockroach species. For each species, 3 replicates of 6 adult male cockroaches were confined in 0.91 glass jars coated with a thin layer of petroleum jelly along the upper inside margin and provisioned with a 65 ml watering jar, Purina dog chow, paper toweling, and one 1.4 g piece of bait. The cockroaches were kept at 29°C in constant darkness. Mortality in each jar was recorded daily and dead individuals were removed. When all the cockroaches died, the bait was removed and weighed and the average mg of bait consumed per male calculated as the average difference between the initial and final weight of the bait.
Laboratory Evaluation of IGRs Against Larval Cat Fleas, 1982
Authors: Rust Michael K. , Reierson Donald A.
Published: March 2022

The biological activity of the insect growth regulators (IGR) Precor 5E, RO 13-5223, and MV-678 against larval fleas was determined after application to filter paper or fabric and after being mixed with larval rearing medium. For surface contact-tests, discs of Whatman No. 1 filter paper or 100% cotton fabric (9 cm diam) were evenly treated with 6.3 × 10-5 and 6.3 × 10-7% IGR-acetone solution. These concentrations provided 0.5 and 0.005 ug ai/cm2 deposits, respectively. Sufficient deposits were prepared so that each deposit was only tested once. For tests with treated media at 1, 10 and 100 ppm, each IGR was mixed into standard larval medium consisting of dog chow, beef blood, and wheast. Acetone dilutions of IGR (5 ml: 10 g medium) were mixed into the media and allowed to dry 18 h. For each kind of test, larvae about 7 days from pupation (3rd-instar) were confined to each of 3 discs of treated paper or cloth (2 cm diam) placed in the bottom of glass shell vials (8.5 cm × 2 cm diam) provisioned with about 0.25 cc untreated larval rearing medium and 0.25 cc clean sand. To test the activity of treated media, 10 larvae were placed into each of 3 vials provisioned with similar amounts of treated media and sand. Each vial was covered with a paper towel cap and held at 75% RH. The contents of each vial were examined weekly and the number of live and dead larvae, pupae and emerged adults counted.
Azalea Lace Bug Control, 1982
Authors: Schultz P. B.
Published: March 2022

Container-grown 'Hershey red' azaleas infested with lace bug were selected for treatment. Insecticides were applied on Sep 10 using a 1 gal B & G compressed air sprayer, and were applied to runoff. The treatments were evaluated Sep 13 by counting the lace bugs on 6 plants per treatment. Temperature at treatment time was 74°F and no rainfall occurred between application and evaluation.
Imported Cabbageworm Control in Broccoli, 1982
Authors: Cranshaw Whitney S.
Published: March 2022

'Southern Comet' broccoli was transplanted Jun 18 at the Rosemount Agricultural Experiment Station, Rosemount, MN. Plants were spaced 12-inches within row, 40-inches between rows. Plots were single row, 25-ft long, arranged in a randomized complete block with 3 replications. Applications were made Aug 6 or Jul 30 using a CO2 compressed air sprayer delivering 20 gal/acre at 25 psi . Evaluations were made Aug 13 by counting all larvae found in a 5-^head sample collected from each plot.
Control Of LepidoPterous Larvae in Cabbage, 1981
Authors: Cranshaw Whitney S. , Johnston Richard L. , Cuperus Gerrit W. , Radcliffe Edward B.
Published: March 2022

Late Flat Dutch' cabbage was transplanted Jun 9 to 36-in row with a 30-inch in-row spacing at the Rosemount Agricultural Experiment Station, Dakota Co., Minnesota. Three separate trials were conducted. Plot size was 25 row-ft in the first and 2nd trials, 30 row-ft in the 3rd trial. Plots were arranged in a randomized complete block design with 3 replications and border rows separated all plots to minimize effects of drift. Spray applications were made Aug 18, Sep 8, and Sep 22 using a C02 compressed air sprayer delivering 75 gal/acre at 25 psi. Plots were counted Aug 21, Sep 11, and Sep 24 by examining 6-8 heads in a plot.
Harnessing Virtual Reality Nature to Promote Well-Being
Authors: Noronha Hildegardo , Campos Pedro
Published: March 2022

With virtual reality (VR) industries and research focusing on gaming, training and, somewhat, in healthcare, there seems to be a lack of VR as simpler form of relaxing leisure, despite its potential. When emotions are targeted, there appears to be a focus on visceral ones like jump scares, panic, high adrenaline, fears and anything related to bad feelings and instinctive reactions. This study explores and proves that VR can effectively relax the user. We conducted an experiment where the users were exposed to VR-based natural sceneries, and we measured its effect on their positive feelings and relaxation levels. We found evidence, with a high degree of significance, of an increase in calmness and a reduction of arousal and energy. This effect is present in short sessions. We also explored the possibility of VR sunsets affecting our subjects’ circadian rhythm.
Coated tannin supplementation improves growth performance, nutrients digestibility, and intestinal function in weaned piglets
Authors: Xu Tingting , Ma Xin , Zhou Xinchen , Qian Mengqi , Yang Zhiren , Cao Peiwen , Han Xinyan
Published: March 2022

To explore the effect of coated tannin (CT) on the growth performance, nutrients digestibility, and intestinal function in weaned piglets, a total of 180 piglets Duroc × Landrace × Yorkshire (28 d old) weighing about 8.6 kg were randomly allotted to three treatments: 1) Con: basal diet (contains ZnSO4); 2) Tan: basal diet + 0.15% CT; and 3) ZnO: basal diet + ZnO (Zn content is 1,600 mg/kg). The results showed that 0.15% CT could highly increase the average daily gain and average daily feed intake of weaned piglets compared with the control group, especially decreasing diarrhea incidence significantly (P < 0.05). Compared with the control group, crude protein apparent digestibility and digestive enzyme activity of the piglets fed with 0.15% CT were enhanced obviously (P < 0.05). Meanwhile, the intestinal villi and microvilli arranged more densely, while the content of serum diamine oxidase was decreased, and the protein expressions of zonula occludens-1 (ZO-1) and claudin-1 were significantly upregulated (P < 0.05). In addition, CT altered the structure of intestinal microbiota and augmented some butyrate-producing bacteria such as Ruminococcaceae and Megasphaera. PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) analysis also showed that the abundances of pathways related to butyrate metabolism and tryptophan metabolism were increased; however, the function of lipopolysaccharide biosynthesis proteins was significantly decreased. The results demonstrated that 0.15% CT could improve growth performance, digestibility, and intestinal function of weaned piglets, and it had the potential to replace ZnO applied to farming.
American College of Gastroenterology-Canadian Association of Gastroenterology Clinical Practice Guideline: Management of Anticoagulants and Antiplatelets During Acute Gastrointestinal Bleeding and the Periendoscopic Period
Authors: Abraham Neena S , Barkun Alan N , Sauer Bryan G , Douketis James , Laine Loren , Noseworthy Peter A , Telford Jennifer J , Leontiadis Grigorios I
Published: March 2022

We conducted systematic reviews of predefined clinical questions and used the Grading of Recommendations, Assessment, Development and Evaluations approach to develop recommendations for the periendoscopic management of anticoagulant and antiplatelet drugs during acute gastrointestinal (GI) bleeding and the elective endoscopic setting. The following recommendations target patients presenting with acute GI bleeding: For patients on warfarin, we suggest against giving fresh frozen plasma or vitamin K; if needed, we suggest prothrombin complex concentrate (PCC) compared with fresh frozen plasma administration; for patients on direct oral anticoagulants (DOACs), we suggest against PCC administration; if on dabigatran, we suggest against the administration of idarucizumab, and if on rivaroxaban or apixaban, we suggest against andexanet alfa administration; for patients on antiplatelet agents, we suggest against platelet transfusions; and for patients on cardiac acetylsalicylic acid (ASA) for secondary prevention, we suggest against holding it, but if the ASA has been interrupted, we suggest resumption on the day hemostasis is endoscopically confirmed. The following recommendations target patients in the elective (planned) endoscopy setting: For patients on warfarin, we suggest continuation as opposed to temporary interruption (1–7 days), but if it is held for procedures with high risk of GI bleeding, we suggest against bridging anticoagulation unless the patient has a mechanical heart valve; for patients on DOACs, we suggest temporarily interrupting rather than continuing these; for patients on dual antiplatelet therapy for secondary prevention, we suggest temporary interruption of the P2Y12 receptor inhibitor while continuing ASA; and if on cardiac ASA monotherapy for secondary prevention, we suggest against its interruption. Evidence was insufficient in the following settings to permit recommendations. With acute GI bleeding in patients on warfarin, we could not recommend for or against PCC administration when compared with placebo. In the elective periprocedural endoscopy setting, we could not recommend for or against temporary interruption of the P2Y12 receptor inhibitor for patients on a single P2Y12 inhibiting agent. We were also unable to make a recommendation regarding same-day resumption of the drug vs 1–7 days after the procedure among patients prescribed anticoagulants (warfarin or DOACs) or P2Y12 receptor inhibitor drugs because of insufficient evidence.
ZWC complex-mediated SPT5 phosphorylation suppresses divergent antisense RNA transcription at active gene promoters
Authors: Park Kihyun , Zhong Jian , Jang Jin Sung , Kim Jihyun , Kim Hye-Jung , Lee Jeong-Heon , Kim Jaehoon
Published: March 2022

The human genome encodes large numbers of non-coding RNAs, including divergent antisense transcripts at transcription start sites (TSSs). However, molecular mechanisms by which divergent antisense transcription is regulated have not been detailed. Here, we report a novel ZWC complex composed of ZC3H4, WDR82 and CK2 that suppresses divergent antisense transcription. The ZWC complex preferentially localizes at TSSs of active genes through direct interactions of ZC3H4 and WDR82 subunits with the S5p RNAPII C-terminal domain. ZC3H4 depletion leads to increased divergent antisense transcription, especially at genes that naturally produce divergent antisense transcripts. We further demonstrate that the ZWC complex phosphorylates the previously uncharacterized N-terminal acidic domain of SPT5, a subunit of the transcription-elongation factor DSIF, and that this phosphorylation is responsible for suppressing divergent antisense transcription. Our study provides evidence that the newly identified ZWC-DSIF axis regulates the direction of transcription during the transition from early to productive elongation.
Predictive modeling of resistance to SMO inhibition in a patient-derived orthotopic xenograft model of SHH medulloblastoma
Authors: Krausert Sonja , Brabetz Sebastian , Mack Norman L , Schmitt-Hoffner Felix , Schwalm Benjamin , Peterziel Heike , Mangang Aileen , Holland-Letz Tim , Sieber Laura , Korshunov Andrey , Oehme Ina , Jäger Natalie , Witt Olaf , Pfister Stefan M , Kool Marcel
Published: March 2022

Background

Inhibition of the sonic hedgehog (SHH) pathway with Smoothened (SMO) inhibitors is a promising treatment strategy in SHH-activated medulloblastoma, especially in adult patients. However, the problem is that tumors frequently acquire resistance to the treatment. To understand the underlying resistance mechanisms and to find ways to overcome the resistance, preclinical models that became resistant to SMO inhibition are needed.

Methods

To induce SMO inhibitor resistant tumors, we have treated a patient-derived xenograft (PDX) model of SHH medulloblastoma, sensitive to SMO inhibition, with 20 mg/kg Sonidegib using an intermitted treatment schedule. Vehicle-treated and resistant models were subjected to whole-genome and RNA sequencing for molecular characterization and target engagement. In vitro drug screens (76 drugs) were performed using Sonidegib-sensitive and -resistant lines to find other drugs to target the resistant lines. One of the top hits was then validated in vivo.

Results

Nine independent Sonidegib-resistant PDX lines were generated. Molecular characterization of the resistant models showed that eight models developed missense mutations in SMO and one gained an inactivating point mutation in MEGF8, which acts downstream of SMO as a repressor in the SHH pathway. The in vitro drug screen with Sonidegib-sensitive and -resistant lines identified good efficacy for Selinexor in the resistant line. Indeed, in vivo treatment with Selinexor revealed that it is more effective in resistant than in sensitive models.

Conclusions

We report the first human SMO inhibitor resistant medulloblastoma PDX models, which can be used for further preclinical experiments to develop the best strategies to overcome the resistance to SMO inhibitors in patients.
Ontogeny of the skeleton of Moenkhausia pittieri (Ostariophysi: Characiformes) with discussion on functional demands and ossification patterns in the Characidae
Authors: Marinho Manoela M F
Published: March 2022

Most fishes must face their environment alone in the early stages of life. The overall sequence of bone appearance is related to functional demands of the early developmental stages. This study offers detailed data on the skeletogenesis of Moenkhausia pittieri, as an example of a "generalized characid". The sequence of ossification is determined and discussed in response to functional demands. Early developmental stages involve the rapid development of bones related to respiration and feeding. The last sets of bones to appear include those of the paired fins and infraorbitals. Patterns in the order of ossification are highlighted, and heterochronies are detected and discussed. Loss of late developmental stages related to miniaturization, a trend in the evolution of Characidae, is discussed in the light of comparative anatomy and ontogenetic data. Furthermore, morphological particularities found in M. pittieri and other characids are discussed in an ontogenetic perspective, offering a background for future phylogenetic studies to understand the homology of certain structures and serving as a further step to elucidate the relationships in ostariophysans.
Quantifying Head and Neck Lymphatic Malformation Volume and Composition During Treatment
Authors: Konuthula Neeraja , Bindschadler Michael , Perez Francisco A. , Shivaram Giri M. , Bly Randall A. , Friedman Seth D. , Perkins Jonathan A.
Published: March 2022

Objective:

Head and neck lymphatic malformation (HNLM) treatment involves a combination of observation, surgery, sclerotherapy, and targeted medical therapy. Objective comparison of these differing treatments is unstandardized due to heterogeneity of HNLM location, size, and variable components. Our objective was to develop a protocol for standardized assessment of magnetic resonance imaging (MRI) image sets through novel semiautomated algorithms. We aimed to obtain reproducible multimodal tissue level data that can be analyzed for interval HNLM treatment response.

Methods:

Patients who were undergoing therapy for HNLM were queried from an institutional database between 2015 and 2020. MRI sequences were registered in 3D Slicer, and in MATLAB a multimodal tool was developed to quantitate HNLM volume and changes in composition. Volume measures were normalized to normal childhood growth using the nasion-basion distance. Reproducibility studies were conducted to evaluate interrater reliability.

Results:

HNLM undergoing excision (n = 3) had a 92.3%–96.7% decrease malformation volume. HNLM having medical treatment with sirolimus and aspirin had a 7.3%–36.4% decrease in normalized volume, the majority of which was due to a decrease in cystic fluid content (reduced by 27.0%–36.4%). HNLM treated with sclerotherapy had no normalized volume change following treatment. One HNLM first treated with sirolimus had a 27.8% decrease in normalized volume and then combined normalized volume reduction of 75.6% after resection.

Conclusion:

This proof-of-concept use of longitudinal HNLM MRI in pediatric patients undergoing treatment demonstrates that objective information can be obtained through this method. This information can be used to determine treatment efficacy and optimize lesion specific treatment strategies.
Laparoscopic Training for Gastrointestinal Surgery Using Japanese Traditional Papercraft Origami
Authors: Hiraki Masatsugu , Kimura Naoya , Kitagawa Hiroshi , Kohya Naohiko , Samejima Ryuichiro
Published: March 2022

Purpose:

The aim of this study is to show the experience and results of laparoscopic training using origami, a Japanese traditional papercraft, and to discuss its usefulness in gastrointestinal surgery.

Materials and Methods:

A laparoscopic training dry box was used. An origami paper crane was folded using laparoscopic instruments. The time to complete the origami crane was measured.

Results:

Two trainees participated in this study; the total number of origami cranes folded by these trainees was 2000 and 700, respectively. The learning curve gradually improved. According to our experience, this training strengthened mental faculties and was associated with the improvement of hand-eye and left-right coordination, reduction of tremor, acquisition of delicate technique, the ability to distinguish subtle differences in color, ability to respond to trouble.

Conclusions:

Laparoscopic training for gastrointestinal surgery using origami may have the potential to improve the technical skills in laparoscopic surgery.
Meta-analysis of the Ralstonia solanacearum species complex (RSSC) based on comparative evolutionary genomics and reverse ecology
Authors: Sharma Parul , Johnson Marcela A. , Mazloom Reza , Allen Caitilyn , Heath Lenwood S. , Lowe-Power Tiffany M. , Vinatzer Boris A.
Published: March 2022

Ralstonia solanacearum

species complex (RSSC) strains are bacteria that colonize plant xylem tissue and cause vascular wilt diseases. However, individual strains vary in host range, optimal disease temperatures and physiological traits. To increase our understanding of the evolution, diversity and biology of the RSSC, we performed a meta-analysis of 100 representative RSSC genomes. These 100 RSSC genomes contain 4940 genes on average, and a pangenome analysis found that there are 3262 genes in the core genome (~60 % of the mean RSSC genome) with 13 128 genes in the extensive flexible genome. A core genome phylogenetic tree and a whole-genome similarity matrix aligned with the previously named species (

R. solanacearum

,

R. pseudosolanacearum

,

R. syzygii

) and phylotypes (I–IV). These analyses also highlighted a third unrecognized sub-clade of phylotype II. Additionally, we identified differences between phylotypes with respect to gene content and recombination rate, and we delineated population clusters based on the extent of horizontal gene transfer. Multiple analyses indicate that phylotype II is the most diverse phylotype, and it may thus represent the ancestral group of the RSSC. We also used our genome-based framework to test whether the RSSC sequence variant (sequevar) taxonomy is a robust method to define within-species relationships of strains. The sequevar taxonomy is based on alignments of a single conserved gene (egl). Although sequevars in phylotype II describe monophyletic groups, the sequevar system breaks down in the highly recombinogenic phylotype I, which highlights the need for an improved, cost-effective method for genotyping strains in phylotype I. Finally, we enabled quick and precise genome-based identification of newly sequenced RSSC strains by assigning Life Identification Numbers (LINs) to the 100 strains and by circumscribing the RSSC and its sub-groups in the LINbase Web service.
Prevention of SARS-CoV-2 airborne transmission in a workplace based on CO2 sensor network
Authors: Yokogawa Shinji , Ishigaki Yo , Kitamura Hiroko , Saito Akira , Kawauchi Yuto , Hiraide Taisei
Published: March 2022

We measured the compartmental air change per hour (ACH) using a CO2 sensor network in an office space where a cluster of COVID-19 infections attributed to aerosol transmission occurred. Generalized linear mixed models and dynamic time warping were used for a time series data analysis, and the results indicated that the ventilation conditions were poor at the time of the cluster outbreak, and that the low ACH in the room likely contributed to the outbreak. In addition, the adverse effects of inappropriate partitions and the effectiveness of ventilation improvements were investigated in detail. ACH of less than 2 /h was considered a main contributor for the formation of the COVID-19 cluster in the studied facility.

Practical Implications

A systematic method for measuring and evaluating indoor ventilation to prevent the spread of infectious diseases caused by aerosols is presented. Ventilation bias caused by ventilation pathways and inappropriate use of plastic sheeting can be detected by a CO2 sensor network and time series data analysis. Estimated ventilation rate will be a good index to suppress the formation of the COVID-19 cluster.
High-throughput molecular dynamics-based alchemical free energy calculations for predicting the binding free energy change associated with the common mutations in the spike receptor-binding domain of SARS-CoV-2
Authors: Bhadane Rajendra , Salo-Ahen Outi M. H.
Published: March 2022

The ongoing pandemic caused by SARS-CoV-2 has gone through various phases. From the initial outbreak the virus has mutated several times, with some lineages showing even stronger infectivity and faster spread than the original virus. Among all the variants, beta, gamma, delta and the latest (omicron) are currently classified as variants of concern (VOC) while the remaining are labelled either as variants of interest (VOI) or variants under monitoring (VUM). In this work, we have focused on the mutations observed in important variants, particularly at the receptor-binding domain (RBD) of the spike protein that is responsible for the interactions with the host ACE2 receptor and binding of antibodies. Studying these mutations is particularly important for understanding the viral infectivity, spread of the disease and for tracking the escape routes of this virus from antibodies. Molecular dynamics (MD) based alchemical free energy calculations have been shown to be very accurate in predicting the free energy change due to a mutation that could have a deleterious or a stabilising effect on the protein itself or its binding affinity to another protein. Here, we investigated the significance of six commonly observed spike RBD mutations on the stability of the spike protein binding to ACE2 by free energy calculations using high throughput MD simulations. For comparison, we also used other (rigorous and non-rigorous) binding free energy prediction methods and compared our results with the experimental data if available. The alchemical free energy-based method consistently predicted the free-energy changes with an accuracy close to ±1.0 kcal/mol when compared with the available experimental values. As per our simulation data the most significant mutations responsible for stabilising the spike RBD interactions with human ACE2 are N501Y and L452R.
The acid ceramidase/ceramide axis controls parasitemia in Plasmodium yoelii-infected mice by regulating erythropoiesis
Authors: Günther Anne , Hose Matthias , Schumacher Fabian , Kleuser Burkhard , Matuschewski Kai , Lang Karl S. , Gulbins Erich , Buer Jan , Westendorf Astrid M. , Hansen Wiebke
Published: March 2022

Acid ceramidase (Ac) is part of the sphingolipid metabolism and responsible for the degradation of ceramide. As bioactive molecule, ceramide is involved in the regulation of many cellular processes. However, the impact of cell-intrinsic Ac activity and ceramide on the course of Plasmodium infection remains elusive. Here, we use Ac-deficient mice with ubiquitously increased ceramide levels to elucidate the role of endogenous Ac activity in a murine malaria model. Interestingly, ablation of Ac leads to alleviated parasitemia associated with decreased T cell responses in the early phase of Plasmodium yoelii (P. yoelii) infection. Mechanistically, we identified dysregulated erythropoiesis with reduced numbers of reticulocytes, the preferred host cells of P. yoelii, in Ac-deficient mice. Furthermore, we demonstrate that administration of the Ac inhibitor carmofur to wild type mice has similar effects on P. yoelii infection and erythropoiesis. Notably, therapeutic carmofur treatment after manifestation of P. yoelii infection is efficient in reducing parasitemia. Hence, our results provide evidence for the involvement of Ac and ceramide in controlling P. yoelii infection by regulating red blood cell development.
Unified classification and risk-stratification in Acute Myeloid Leukemia
Authors: Tazi Yanis , Arango Ossa Juan , Zhou Yangyu , Bernard Elsa , Thomas Ian , Gilkes Amanda , Freeman Sylvie , Pradat Yoann , Johnson Sean , Hills Robert , Dillon Richard , Levine Max , Leongamornlert Dan , Butler Adam , Ganser Arnold , Bullinger Lars , Dohner Konstanze , Ottmann Oliver , Adams Richard , Dohner Hartmut , Campbell Peter , Burnett Alan , Dennis Michael , Russell Nigel , Devlin Sean , Huntly Brian , Papaemmanuil Elli
Published: March 2022

Clinical recommendations for AML classification and risk-stratification remain heavily reliant on cytogenetic findings at diagnosis, which are present in <50% of patients. Using comprehensive molecular profiling data from 3,653 patients we characterize and validate 16 molecular classes describing 100% of AML patients. Each class represents diverse biological AML subgroups, and is associated with distinct clinical presentation, likelihood of response to induction chemotherapy, risk of relapse and death over time. Secondary AML-2, emerges as the second largest class (24%), associates with high-risk disease, poor prognosis irrespective of flow MRD negativity, and derives significant benefit from transplantation. Guided by class membership we derive a 3-tier risk-stratification score that re-stratifies 26% of patients as compared to standard of care. This results in a unified framework for disease classification and risk-stratification in AML that relies on information from cytogenetics and 32 genes. Last, we develop an open-access patient-tailored clinical decision support tool.
Pharmacokinetics of favipiravir in adults with mild COVID-19 in Thailand
Authors: Manosuthi Weerawat , Prasanchaimontri Ing-orn , Niyomnaitham Suvimol , Sirijatuphat Rujipas , Charoenpong Lantharita , Copeland Katherine , Cressey Tim R. , Mokmued Phongpan , Chokephaibulkit Kulkanya
Published: March 2022

We assessed the pharmacokinetics of favipiravir (FPV) in adults with symptomatic SARS-CoV-2 infection without pneumonia in Thailand. FPV dosing was 1800 mg twice-daily on day 1, then 800 mg twice-daily for 14 days. Eight subjects (7 female), median (range) age 39 (19-53) years and BMI 27.9 (18.0-33.6) were included. Inter-subject variability was high but all achieved minimum plasma concentrations (Cmin) above EC50(9.7 mg/L). FPV was well tolerated; 1 subject stopped prematurely due to rash.
Possible Role of P-selectin Adhesion in Long-COVID: A Comparative Analysis of a Long-COVID Case Versus an Asymptomatic Post-COVID Case
Authors: Tarasev Michael , Mota Sabrina , Gao Xiufeng , Ferranti Marta , Zaidi Aliya U. , Hannan Bryan , Hines Patrick
Published: March 2022

Background

Long-term outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are now recognized as an emerging public health challenge - a condition termed Long-COVID. The pathophysiology of Long-COVID remains to be established. Functional P-selectin activity, implicated in COVID-19 sequalae, was measured between two convalescent COVID-19 subjects, one with (Long-COVID subject) and another without Long-COVID symptoms.

Methods

Flow adhesion of whole blood or isolated white blood cells to P-selectin (FA-WB-Psel and FA-WBC-Psel) was measured using a standardized microfluidics clinical assay; impedance aggregometry with a collagen agonist was measured using model 590 Chrono-Log impedance aggregometer; standard laboratory assays were performed to evaluate changes in blood chemistries.

Results

For both subjects, hemoglobin, WBC, platelet counts, electrolytes and ferritin were within normal reference ranges, with FA-WB-Psel significantly elevated compared to healthy controls (p< 0.01). In vitro treatment of whole blood samples with crizanlizumab (anti-p-selectin monoclonal antibody) within the clinical dose range (10 μg/ml) mL) inhibited FA-WB-Psel only in samples from asymptomatic post-COVID subject, with the Long-COVID subject sample requiring close to 5-fold elevated dose to achieve a response. Pronounced inhibition of P-selectin adhesion of isolated leukocytes was observed for both subjects in autologous platelet-poor plasma and buffer. Impedance aggregometry showed greater baseline platelet aggregation to collagen in the Long-COVID sample, although both samples responded similarly to aspirin-induced platelet inhibition.

Conclusions

Presented results suggest that elevated platelet activation in Long-COVID subject may be associated with increased P-Selectin activity. The results are discussed in terms of possible use on P-selectin inhibition therapies in treating Long-COVID.
Haploinsufficiency underlies the neurodevelopmental consequences ofSLC6A1/GAT-1 variants
Authors: Silva Dina Buitrago , Trinidad Marena , Ljungdahl Alicia , Revalde Jezrael L. , Berguig Geoffrey Y. , Wallace William , Patrick Cory S. , Bomba Lorenzo , Arkin Michelle , Dong Shan , Estrada Karol , Hutchinson Keino , LeBowitz Jonathan H. , Schlessinger Avner , Johannesen Katrine M. , Møller Rikke S. , Giacomini Kathleen M. , Froelich Steven , Sanders Stephan J. , Wuster Arthur
Published: March 2022

Heterozygous variants in the GAT-1 GABA transporter encoded bySLC6A1are associated with seizures, developmental delay, and autism. The majority of affected individuals carry missense variants, many of which are recurrent germlinede novomutations, raising the possibility of gain-of-function effects. To understand the functional consequences, we performed anin vitroGABA uptake assay for 213 unique variants, including 24 control variants.De novovariants consistently resulted in a decrease in GABA uptake, in keeping with haploinsufficiency underlying all neurodevelopmental phenotypes. Where present, ClinVar pathogenicity reports correlated well with GABA uptake data; the functional data can inform future reports for the remaining 72% of unscored variants. Surface expression was assessed for 86 variants; two-thirds of loss-of-function missense variants prevented GAT-1 from being present on the membrane while GAT-1 was on the surface but with reduced activity for the remaining third. Surprisingly, recurrentde novomissense variants showed moderate loss-of-function effects that reduced GABA uptake with no evidence for dominant negative or gain-of-function effects. Using linear regression across multiple missense severity scores to extrapolate the functional data to all potentialSLC6A1missense variants, we observe an abundance of GAT-1 residues that are sensitive to substitution. The extent of this missense vulnerability accounts for the clinically observed missense enrichment; overlap with hypermutable CpG sites accounts for the recurrent missense variants. Strategies to increase the expression of the wildtypeSLC6A1allele are likely to be beneficial across neurodevelopmental disorders, though the developmental stage and extent of required rescue remain unknown.
Using remotely delivered Spring Forest Qigong™ to reduce neuropathic pain in adults with spinal cord injury: Protocol of a quasi-experimental clinical trial
Authors: Van de Winckel Ann , Carpentier Sydney , Deng Wei , Zhang Lin , Battaglino Ricardo , Morse Leslie
Published: March 2022

Background

About 69% of Americans living with spinal cord injury (SCI) suffer from long-term debilitating neuropathic pain, interfering with the quality of daily life. Neuropathic pain is refractory to many available treatments –some carrying a risk for opioid addiction– highlighting an urgent need for new treatments. In this study, we will test our hypothesis that Spring Forest QigongTMwill reduce SCI-related neuropathic pain by improving body awareness. We will determine whether remotely delivered Qigong isfeasibleand we will collect data on neuropathic pain, and other reported associations with pain such as spasms frequency and/or severity, functional performance, mood, or body awareness.

Methods

In this quasi-experimental pilot clinical trial study, adults with SCI will practice Qigong at home with a 45min video, at least 3x/week for 12 weeks. The Qigong practice includes movements with guided breathing and is individualized based on functional abilities, i.e., the participants follow along with the Qigong movements to the level of their ability, with guided breathing, and perform kinesthetic imagery by focusing on the feeling in the whole body as if doing the whole-body Qigong movement while standing. The highest, average, and lowest neuropathic pain ratings perceived in the prior week will be recorded weekly until the 6-week follow-up. The other outcomes will be collected at 5 time points: at baseline, midway during the Qigong intervention (6 weeks), after the Qigong intervention (12 weeks), after a 6-week and 1-year follow-up. Rate parameters for the feasibility markers will be estimated based on the participants who achieved each benchmark.

Discussion

The University of Minnesota (UMN)’s Institutional Review Board (IRB) approved the study (IRB #STUDY00011997). All participants will sign electronic informed consent on the secure UMN REDCap platform. The results will be presented at academic conferences and published in peer-reviewed publications.

Trial registration

ClinicalTrial.govregistration number:NCT04917107, first registered 6/8/2021,https://clinicaltrials.gov/ct2/show/NCT04917107.
Development of medical device software for the screening and assessment of depression severity using data collected from a wristband-type wearable device: SWIFT study protocol
Authors: Kishimoto Taishiro , Kinoshita Shotaro , Kikuchi Toshiaki , Bun Shogyoku , Kitazawa Momoko , Horigome Toshiro , Tazawa Yuki , Takamiya Akihiro , Hirano Jinichi , Mimura Masaru , Liang Kuo-ching , Koga Norihiro , Ochiai Yasushi , Ito Hiromi , Miyamae Yumiko , Tsujimoto Yuiko , Sakuma Kei , Kida Hisashi , Miura Gentaro , Kawade Yuko , Goto Akiko , Yoshino Fumihiro
Published: March 2022

Introduction

Few biomarkers can be clinically used to diagnose and assess the severity of depression. However, a decrease in activity and sleep efficiency can be observed in depressed patients, and recent technological developments have made it possible to measure these changes. In addition, physiological changes, such as heart rate variability, can be used to distinguish depressed patients from normal persons; these parameters can be used to improve diagnostic accuracy. The proposed research will explore and construct machine learning models capable of detecting depressive episodes and assessing their severity using data collected from wristband-type wearable devices.

Methods

Patients with depressive symptoms and healthy subjects will wear a wristband-type wearable device for 7 days; data on triaxial acceleration, pulse rate, skin temperature, and ultraviolet light will be collected. On the seventh day of wearing, the severity of depressive episodes will be assessed using SCID-5, HAMD, and other scales. Data for up to five 7-day periods of device wearing will be collected from each subject. Using wearable device data associated with clinical symptoms as supervisory data, we will explore and build a machine learning model capable of identifying the presence or absence of depressive episodes and predicting the HAMD scores for an unknown data set.

Discussion

Our machine learning model could improve the clinical diagnosis and management of depression through the use of a wearable medical device.

Trial Registration

jRCT1031210478, Japan Registry of Clinical Trials (jRCT)
Plasma metabolites associated with cognitive function across race/ethnicities affirming the importance of healthy nutrition
Authors: Granot-Hershkovitz Einat , He Shan , Bressler Jan , Yu Bing , Tarraf Wassim , Rebholz Casey M. , Cai Jianwen , Chan Queenie , Garcia Tanya P. , Mosley Thomas , Kristal Bruce S. , DeCarli Charles , Fornage Myriam , Chen Guo-Chong , Qi Qibin , Kaplan Robert , Gonzalez Hector M. , Sofer Tamar
Published: March 2022

INTRODUCTION

We studied the replication and generalization of previously identified metabolites potentially associated with global cognitive function in multiple race/ethnicities and assessed the contribution of diet to these associations.

METHODS

We tested metabolite-cognitive function associations in U.S.A. Hispanic/Latino adults (n= 2,222) from the Community Health Study/ Study of Latinos (HCHS/SOL) and in European (n=1,365) and African (n=478) Americans from the Atherosclerosis Risk In Communities (ARIC) Study. We applied Mendelian Randomization (MR) analyses to assess causal associations between the metabolites and cognitive function and between Mediterranean diet and cognitive function.

RESULTS

Six metabolites were consistently associated with lower global cognitive function across all studies. Of these, four were sugar related (e.g., ribitol). MR analyses provided weak evidence for a potential causal effect of ribitol on cognitive function and bi-directional effects of cognitive performance on diet.

DISCUSSION

Several diet-related metabolites were associated with global cognitive function across studies with different race/ethnicities.