bluuebunny/crossref_metadata_2025 huggingface dataset:
Tenofovir disoproxil fumarate on the risk of hepatocellular carcinoma in chronic hepatitis B patients with failure to preceding treatments: A nationwide cohort study
Authors: Lee Jayoun , Kim Gi‐Ae , Kim Hyo Jeong , Cho Songhee , Ko Min Jung , Lim Young‐Suk
Published: May 2021

Tenofovir disoproxil fumarate (TDF) monotherapy is recommended for the treatment of chronic hepatitis B (CHB) patients who are refractory to other drugs. Yet, little data are available for the effectiveness of TDF monotherapy compared with TDF‐based combination therapy on the risk of hepatocellular carcinoma (HCC) and death/transplantation. This nationwide population‐based cohort study included 11,289 CHB patients who initiated TDF rescue therapy after failure of preceding treatments between 2012 and 2014 in Korea. The risks of HCC and death/transplantation were compared between TDF combotherapy (n = 2,499) and TDF monotherapy (n = 8,790) groups. The findings were validated in a hospital cohort of 1,163 CHB patients. In the nationwide cohort, during 44.2 months of overall treatment duration, 529 patients developed HCC and 190 died or received transplantation. In the 2,499 propensity score‐matched pairs, compared with TDF combotherapy, TDF monotherapy showed no significantly different risks of HCC (1.11/100 person‐year [PY] vs. 1.32/100 PY; HR 1.23, 95% CI 0.95−1.60, p = .12) and death/transplant (0.43/100 PY vs. 0.42/100 PY; HR 1.04, 95% CI 0.67−1.60, p = .87). However, in the 469 propensity score‐matched pairs of cirrhosis subcohort, TDF monotherapy was associated with a higher risk of HCC than TDF combotherapy (HR 1.46, 95% CI 1.002−2.12, p = .049). In the validation hospital cohort, TDF monotherapy was not associated with significantly different risks of HCC and death/transplant in the entire cohort and cirrhosis subcohort. In CHB patients with failure to preceding treatments, TDF monotherapy showed no higher risks of HCC and death/transplantation compared with TDF combotherapy. However, the comparative effectiveness of rescue TDF monotherapy should be further clarified in cirrhotic patients since the findings were not consistent in the nationwide and hospital cohorts.
Lymphoplasmacytic and eosinophilic enteritis with or without globule leukocyte hyperplasia in 4 goats
Authors: Pitel Mariya O. , Heller Meera C. , Roberson Jerry R. , McKenzie Erica C. , Sinnott Devinn M. , Affolter Verena K.
Published: May 2021

Four, mature, client‐owned goats were presented to referral hospitals for recurrent diarrhea despite treatment for intestinal parasitism. Common clinical findings included diarrhea, poor condition, neutrophilia, and hypoalbuminemia. Testing for common infectious causes of diarrhea in goats was negative. Ultrasonography and computed tomography in 2 cases was suggestive of enteritis, including thickened intestinal walls and fluid filled, dilated small intestines, respectively. Lymphoplasmacytic and eosinophilic enteritis (LEE) was ultimately diagnosed on intestinal biopsy histopathology based on the presence of small intestinal villous blunting and increased numbers of lymphocytes and eosinophils predominantly within the lamina propria. Numerous globule leukocytes were also noted on histopathology in 3 cases. All goats responded favorably to corticosteroid treatment with weight gain and resolution of diarrhea and clinicopathologic abnormalities. Relapses occurred, and complete cure was difficult to achieve. Reported in other species, this series describes the clinical presentation, diagnosis, and treatment of LEE in adult goats.
Treatment of a flunixin meglumine overdose with intravenous administration of lipid emulsion and therapeutic plasma exchange in a Nigerian dwarf buck kid (Capra aegagrus hircus)
Authors: Butty Emmanuelle Marie , McKinney Caroline Ann , Prisk Amanda Jane
Published: May 2021

A 12 week‐old Nigerian dwarf (Capra aegagrus hircus) buck kid was hospitalized for management of obstructive urolithiasis. Postoperatively, he was inadvertently administered 16‐times greater than his calculated dose of a nonsteroidal anti‐inflammatory drug (NSAID; 17.5 mg/kg flunixin meglumine, IV). The goat was treated with intravenous administration of lipid emulsion (ILE) prior to membrane‐based therapeutic plasma exchange (mTPE) under general anesthesia. The increased coagulability inherent to small ruminants in comparison with dogs and cats warranted specific adjustments in the prescription of anticoagulation, blood flow, and filtration fraction to avoid circuit clotting during mTPE. Serum flunixin meglumine concentration measured before, during, and after mTPE revealed marked reduction in drug concentration. After the combined treatments, no clinical evidence of NSAID gastrointestinal or renal toxicosis was detected. This case report describes successful management of flunixin meglumine overdose in a small ruminant using combined ILE and mTPE.
Heterobilharzia americanainfection in dogs: A retrospective study of 60 cases (2010‐2019)
Authors: Graham Amber M. , Davenport Amy , Moshnikova Valentina S. , Gilmour Lindsey J. , Fabiani Michelle , Bishop Micah A. , Cook Audrey K.
Published: May 2021

Background

The trematodeHeterobilharzia americana(HA) causes granulomatous gastrointestinal and hepatic disease in dogs. Before 2008, diagnosis relied on saline fecal sedimentation or histopathology, and earlier reports primarily described dogs with advanced disease or cases diagnosed incidentally at necropsy. The advent of a fecal PCR test has facilitated the diagnosis ofHAand provided insights into manifestations and response to treatment.

Objectives

Describe the clinical findings, response to treatment, and outcome for dogs infected withHA.

Animals

Sixty dogs diagnosed withHAbetween 2010 and 2019.

Methods

Retrospective study. Medical records were searched for dogs diagnosed withHAby fecal PCR testing, identification of ova in feces, or histopathology.

Results

Mean age was 7.5 (±4.1) years and weight was 23.2 (±10.18) kg. Clinical signs included diarrhea (55.8%), vomiting (46.2%), and weight loss with or without anorexia (15.4%). Laboratory abnormalities included hyperglobulinemia (42.6%) and increased liver enzyme activities (30%). More than 40% of dogs had an eosinophil count >500/μL. Hypercalcemia attributable toHAwas identified in only 4 dogs. Pinpoint hyperechoic foci were noted in intestines, liver, or mesenteric lymph nodes during transabdominal ultrasonography in 64.4% of dogs. Survival data was available for 34 dogs, of which 73.5% (25) were alive 6 months after diagnosis.

Conclusions and Clinical Importance

Hyperglobulinemia, high eosinophil count, and ultrasonographic evidence of visceral mineralization were suggestive of infection. Hypercalcemia was uncommon. Combination treatment with praziquantel and fenbendazole was variably effective, and 17.6% of treated dogs with known outcome died as a result ofHAinfection.
How do secondary iron enrichments form within basaltic eucrites? An experimental approach
Authors: Rombeck Stella , Vollmer Christian , Roszjar Julia , Sarafian Adam R. , Klemme Stephan
Published: May 2021

Some basaltic eucrites and basaltic lithologies in howardites derived from the asteroid 4 Vesta exhibit unusual secondary veinlet textures consisting mostly of fayalitic olivine and Fe‐enrichments within pyroxenes. Recent studies discussed the formation of these Fe‐rich phases either by interaction with a vapor and/or liquid phase (metasomatism), or by a high‐temperature melting process. We therefore performed a series of heating and hydrothermal experiments with liquids of different compositions on natural pyroxene crystals (augite and orthopyroxene) to evaluate these contrasting hypotheses. The results of the heating experiments show that incongruent melting of pyroxenes at about 1070 °C causes textures that are very similar to those observed in the meteorites. We conclude that a part of the natural secondary veins might be explained by heating processes at similar temperatures. The hydrothermal experiments with aqueous liquids of different Fe‐enriched compositions clearly indicate ion exchange reactions resulting in partial Fe‐enrichments of the pyroxene. Interestingly, these Fe‐enrichments occurred independent of the Fe content of the liquid, which can be explained by an internal origin of Fe from the pyroxenes. In one hydrothermal experiment of augite with Fe‐oxalate solution, deposition of fayalitic olivine was observed. From our experimental observations, we conclude that aqueous liquids are plausible candidates for explaining the deposition of Fe‐enrichments and fayalitic olivine inside the fractures of pyroxene. However, we cannot rule out a high‐temperature melting process slightly above the peritectic point of pyroxene to explain a fraction of observed secondary Fe‐enrichments.
Comparing divergence landscapes from reduced‐representation and whole genome resequencing in the yellow‐rumped warbler (Setophaga coronata) species complex
Authors: Szarmach Stephanie J. , Brelsford Alan , Witt Christopher C. , Toews David P.L.
Published: May 2021

Researchers seeking to generate genomic data for non‐model organisms are faced with a number of trade‐offs when deciding which method to use. The selection of reduced representation approaches versus whole genome resequencing will ultimately affect the marker density, sequencing depth, and the number of individuals that can multiplexed. These factors can affect researchers’ ability to accurately characterize certain genomic features, such as landscapes of divergence—how FST varies across the genomes. To provide insight into the effect of sequencing method on the estimation of divergence landscapes, we applied an identical bioinformatic pipeline to three generations of sequencing data (GBS, ddRAD, and WGS) produced for the same system, the yellow‐rumped warbler species complex. We compare divergence landscapes generated using each method for the myrtle warbler (Setophaga coronata coronata) and the Audubon's warbler (S. c. auduboni), and for Audubon's warblers with deeply divergent mtDNA resulting from mitochondrial introgression. We found that most high‐FST peaks were not detected in the ddRAD data set, and that while both GBS and WGS were able to identify the presence of large peaks, WGS was superior at a finer scale. Comparing Audubon's warblers with divergent mitochondrial haplotypes, only WGS allowed us to identify small (10–20 kb) regions of elevated differentiation, one of which contained the nuclear‐encoded mitochondrial gene NDUFAF3. We calculated the cost per base pair for each method and found it was comparable between GBS and WGS, but significantly higher for ddRAD. These comparisons highlight the advantages of WGS over reduced representation methods when characterizing landscapes of divergence.
The amino acid permease (AAP) genes CsAAP2A and SlAAP5A/B are required for oomycete susceptibility in cucumber and tomato
Authors: Berg Jeroen A. , Hermans Freddy W. K. , Beenders Frank , Abedinpour Hanieh , Vriezen Wim H. , Visser Richard G. F. , Bai Yuling , Schouten Henk J.
Published: May 2021

Cucurbit downy mildew (DM), caused by the obligate biotroph Pseudoperonospora cubensis, is a destructive disease in cucumber. A valuable source of DM resistance is the Indian cucumber accession PI 197088, which harbours several quantitative trait loci (QTLs) contributing to quantitatively inherited DM resistance. With a combination of fine‐mapping and transcriptomics, we identified Amino Acid Permease 2A (CsAAP2A) as a candidate gene for QTL DM4.1.3. Whole‐genome and Sanger sequencing revealed the insertion of a Cucumis Mu‐like element (CUMULE) transposon in the allele of the resistant near‐isogenic line DM4.1.3. To confirm whether loss of CsAAP2A contributes to partial DM resistance, we performed targeting induced local lesions in genomes on a DM‐susceptible cucumber genotype to identify an additional csaap2a mutant, which indeed was partially DM resistant. In view of the loss of the putative function as amino acid transporter, we measured amino acids in leaves. We found that DM‐inoculated leaves of line DM4.1.3 (with the csaap2a mutation) contained significantly fewer amino acids than wild‐type cucumber. The decreased flow of amino acids towards infected leaves in csaap2a plants compared to the wild type might explain the resistant phenotype of the mutant, as this would limit the available nutrients for the pathogen and thereby its fitness. To examine whether AAP genes play a conserved role as susceptibility factors in plant–oomycete interactions, we made targeted mutations in two AAP genes from tomato and studied the effect on susceptibility to Phytophthora infestans. We conclude that not only CsAAP2A but also SlAAP5A/SlAAP5B are susceptibility genes for oomycete pathogens.
Species distribution, azole resistance and related molecular mechanisms in invasive Candida parapsilosis complex isolates: Increase in fluconazole resistance in 21 years
Authors: Demirci‐Duarte Selay , Arikan‐Akdagli Sevtap , Gülmez Dolunay
Published: May 2021

Background

Candida parapsilosis complex consists of three species, the prevalence and geographical distribution of which might vary. Increasing rates of fluconazole resistance among C. parapsilosis complex were reported from various centres.

Objectives

Aim of this study was to identify invasive C. parapsilosis complex strains up to species level, explore rates and molecular mechanisms of azole resistance and analyse temporal changes at a single centre.

Methods

Isolates from blood cultures from 1997 to 2017 were included. Species were identified using RFLP of the SADH gene and confirmed with ITS sequencing when needed. In vitro susceptibility to fluconazole, voriconazole and posaconazole was tested and evaluated using EUCAST guidelines. Sequences of ERG11 and MRR1 genes were analysed for fluconazole non‐susceptible isolates.

Results

A total of 283 isolates from 181 patients were tested for azole susceptibility. All were C. parapsilosis sensu stricto, except one C. orthopsilosis. All three azoles were effective against 213 of the isolates from 135 patients, including one C. orthopsilosis. Fluconazole resistance was 13.3% (24/181 patients). While the first fluconazole‐resistant isolates were detected in 2004, increase was evident after 2011. In ERG11, Y132F mutation was the most common among fluconazole non‐susceptible isolates (71.7%), followed by G458S (10.9%) and D421N (4.3%). In MRR1, R405K (56.5%) and G927C (8.7%) were detected. However, association of these mutations to azole resistance is yet to be investigated.

Conclusions

Rising azole resistance rates in C. parapsilosis sensu stricto isolates particularly after 2011 were of concern. The well‐known Y132F mutation was the predominant mechanism of azole resistance while accompanied with other genetic mutations.
Invasive aspergillosis in solid organ transplantation: Diagnostic challenges and differences in outcome in a Spanish national cohort (Diaspersot study)
Authors: Gioia Francesca , Filigheddu Eta , Corbella Laura , Fernández‐Ruiz Mario , López‐Medrano Francisco , Pérez‐Ayala Ana , Aguado Jose María , Fariñas Maria Carmen , Arnaiz Francisco , Calvo Jorge , Cifrian Jose Maria , Gonzalez‐Rico Claudia , Vidal Elisa , Torre‐Cisneros Julian , Ras Maria Mar , Pérez Sandra , Sabe Nuria , López‐Soria Leyre Monica , Rodríguez‐Alvarez Regino Jose , Montejo José Miguel , Valerio Maricela , Machado Marina , Muñoz Patricia , Linares Laura , Bodro Marta , Moreno Asuncion , Fernández‐Cruz Ana , Cantón Rafael , Moreno Santiago , Martin‐Davila Pilar , Fortún Jesús
Published: May 2021

Background

The diagnosis of invasive aspergillosis (IA) can be problematic in solid organ transplantation (SOT). The prognosis greatly varies according to the type of transplant, and the impact of prophylaxis is not well defined.

Patients and Methods

The Diaspersot cohort analyses the impact of IA in SOT in Spain during the last 10 years. Proven and probable/putative IA was included.

Results

We analysed 126 cases of IA. The incidences of IA were as follows: 6.5%, 2.9%, 1.8% and 0.6% for lung, heart, liver and kidney transplantation, respectively. EORTC/MSG criteria confirmed only 49.7% of episodes. Tree‐in‐bud sign or ground‐glass infiltrates were present in 56.3% of patients, while serum galactomannan (optical density index >0.5) was positive in 50.6%. A total of 41.3% received combined antifungal therapy. Overall mortality at 3 months was significantly lower (p < 0.001) in lung transplant recipients (14.8%) than in all other transplants [globally: 48.6%; kidney 52.0%, liver 58.3%, heart 31.2%, and combined 42.9%]. Fifty‐four percent of episodes occurred despite the receipt of antifungal prophylaxis, and in 10%, IA occurred during prophylaxis (breakthrough infection), with both nebulised amphotericin (in lung transplant recipients) and candins (in the rest).

Conclusions

Invasive aspergillosis diagnostic criteria, applied to SOT patients, may differ from those established for haematological patients. IA in lung transplants has a higher incidence, but is associated with a better prognosis than other transplants. Combination therapy is frequently used for IA in SOT. Prophylactic measures require optimisation of its use within this population.
Incidence and predictors of vascular events following end‐stage kidney disease in childhood
Authors: Le Page Amelia K. , Kennedy Sean E. , Durkan Anne , Chaturvedi Swasti , Walker Amanda , Sypek Matthew P.
Published: May 2021

Aim

Cardiovascular death is a leading cause of mortality in paediatric end‐stage kidney disease (ESKD). There is however little known about the clinically relevant vascular disease in this population. We aimed to describe the incidence of new onset vascular disease and vascular death in Australian children receiving renal replacement therapy (RRT). We also aimed to identify demographic or childhood risk factors for these endpoints, and whether vascular disease predicts mortality.

Methods

Data on Australian patients who commenced RRT at <18 years of age from 1991 to 2017 were extracted from the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA). Multivariable competing risks regression was used to identify factors associated with vascular events.

Results

A cohort of 1268 patients were followed up for a median of 10.31 years. Vascular disease was reported in 5.4%, and vascular death in 4.1%. The cumulative incidence of any vascular event, that is, disease or death, at 10 and 20 years was 5.5% and 12.8%, respectively. Childhood vascular events were associated with non‐Caucasian, non‐Indigenous ethnicity, and for the 804 patients followed up after 18 years of age, vascular events were associated with lack of childhood transplantation, longer childhood dialysis duration and Indigenous ethnicity. Vascular disease was only reported for 25.49% of patients who had a vascular death, and although a significant risk factor for mortality, it had limited ability to predict mortality.

Conclusion

Cumulative incidence of vascular events is significant after commencing RRT during childhood and is associated with ethnicity, longer childhood dialysis duration and lack of childhood transplantation.
Psychometric evaluation of an experience sampling method–based patient‐reported outcome measure in functional dyspepsia
Authors: Klaassen Tim , Smeets Fabienne G. M. , Vork Lisa , Tack Jan , Talley Nicholas J. , Simrén Magnus , Aziz Qasim , Ford Alexander C. , Kruimel Joanna W. , Conchillo José M. , Leue Carsten , Masclee Adrian A. M. , Keszthelyi Daniel
Published: May 2021

Background

Due to important biases, conventional end‐of‐day and end‐of‐week assessment methods of gastrointestinal symptoms in functional dyspepsia (FD) are considered suboptimal. Real‐time symptom assessment based on the experience sampling method (ESM) could be a more accurate measurement method. This study aimed to evaluate validity and reliability of an ESM‐based patient‐reported outcome measure (PROM) for symptom assessment in FD.

Methods

Thirty‐five patients with FD (25 female, mean age 44.7 years) completed the ESM‐based PROM (a maximum of 10 random moments per day) and an end‐of‐day symptom diary for 7 consecutive days. On day 7, end‐of‐week questionnaires were completed including the Nepean Dyspepsia Index (NDI) and Patient Assessment of Gastrointestinal Symptom Severity Index (PAGI‐SYM).

Key Results

Experience sampling method and corresponding end‐of‐day scores for gastrointestinal symptoms were significantly associated (ICCs range 0.770–0.917). However, end‐of‐day scores were significantly higher (Δ0.329–1.031) than mean ESM scores (p < 0.05). Comparing ESM with NDI and PAGI‐SYM scores, correlations were weaker (Pearson's r range 0.467–0.846). Cronbach's α coefficient was good for upper gastrointestinal symptoms (α = 0.842). First half‐week and second half‐week scores showed very good consistency (ICCs range 0.913–0.975).

Conclusion and Inferences

Good validity and reliability of a novel ESM‐based PROM for assessing gastrointestinal symptoms in FD patients was demonstrated. Moreover, this novel PROM allows to evaluate individual symptom patterns and can evaluate interactions between symptoms and environmental/contextual factors. ESM has the potential to increase patients' disease insight, provide tools for self‐management, and improve shared decision making. Hence, this novel tool may aid in the transition toward personalized health care for FD patients.
The acceptability and feasibility of screening, brief intervention, and referral to treatment for pain management among new England veterans with chronic pain: A pilot study
Authors: Sellinger John J. , Martino Steve , Lazar Christina , Mattocks Kristin , Rando Kenneth , Serowik Kristin , Ablondi Karen , Fenton Brenda , Gilstad‐Hayden Kathryn , Brummett Bradley , Holtzheimer Paul E. , Higgins Diana , Reznik Thomas E. , Semiatin Alicia M. , Stapley Todd , Ngo Tu , Rosen Marc I.
Published: May 2021

Objectives

Musculoskeletal disorders often lead to chronic pain in Veterans. Chronic pain puts sufferers at risk for substance misuse, and early intervention is needed for both conditions. This pilot study tested the feasibility and acceptability of a Screening, Brief Intervention, and Referral to Treatment for Pain Management intervention (SBIRT‐PM) to help engage Veterans seeking disability compensation for painful musculoskeletal disorders in multimodal pain treatment and to reduce risky substance use, when indicated.

Methods

This pilot study enrolled 40 Veterans from 8 medical centers across New England in up to 4 sessions of telephone‐based counseling using a motivational interviewing framework. Counseling provided education about, and facilitated engagement in, multimodal pain treatments. Study eligibility required Veterans be engaged in no more than 2 Veteran Affairs (VA) pain treatment modalities, and study participation involved a 12‐week postassessment and semistructured interview about the counseling process.

Results

Majorities of enrolled Veterans screened positive for comorbid depression and problematic substance use. Regarding the offered counseling, 80% of participants engaged in at least one session, with a mean of 3 sessions completed. Ninety percent of participants completed the postassessment. Numerically, most measures improved slightly from baseline to week 12. In semistructured interviews, participants described satisfaction with learning about new pain care services, obtaining assistance connecting to services, and receiving support from their counselors.

Discussion

It was feasible to deliver SBIRT‐PM to Veterans across New England to promote engagement in multimodal pain treatment and to track study outcomes over 12 weeks. Preliminary results suggest SBIRT‐PM was well‐received and has promise for the targeted outcomes.
Isopentenyltransferases as master regulators of crop performance: their function, manipulation, and genetic potential for stress adaptation and yield improvement
Authors: Nguyen Hai Ngoc , Lai Nhan , Kisiala Anna B. , Emery R. J. Neil
Published: May 2021

Isopentenyltransferase (IPT) in plants regulates a rate‐limiting step of cytokinin (CTK) biosynthesis. IPTs are recognized as key regulators of CTK homeostasis and phytohormone crosstalk in both biotic and abiotic stress responses. Recent research has revealed the regulatory function of IPTs in gene expression and metabolite profiles including source‐sink modifications, energy metabolism, nutrient allocation and storage, stress defence and signalling pathways, protein synthesis and transport, and membrane transport. This suggests that IPTs play a crucial role in plant growth and adaptation. In planta studies of IPT‐driven modifications indicate that, at a physiological level, IPTs improve stay‐green characteristics, delay senescence, reduce stress‐induced oxidative damage and protect photosynthetic machinery. Subsequently, these improvements often manifest as enhanced or stabilized crop yields and this is especially apparent under environmental stress. These mechanisms merit consideration of the IPTs as ‘master regulators’ of core cellular metabolic pathways, thus adjusting plant homeostasis/adaptive responses to altered environmental stresses, to maximize yield potential. If their expression can be adequately controlled, both spatially and temporally, IPTs can be a key driver for seed yield. In this review, we give a comprehensive overview of recent findings on how IPTs influence plant stress physiology and yield, and we highlight areas for future research.
Advances in Agrobacterium transformation and vector design result in high‐frequency targeted gene insertion in maize
Authors: Peterson Dave , Barone Pierluigi , Lenderts Brian , Schwartz Chris , Feigenbutz Lanie , St. Clair Grace , Jones Spencer , Svitashev Sergei
Published: May 2021

CRISPR‐Cas is a powerful DNA double‐strand break technology with wide‐ranging applications in plant genome modification. However, the efficiency of genome editing depends on various factors including plant genetic transformation processes and types of modifications desired. Agrobacterium infection is the preferred method of transformation and delivery of editing components into the plant cell. While this method has been successfully used to generate gene knockouts in multiple crops, precise nucleotide replacement and especially gene insertion into a pre‐defined genomic location remain highly challenging. Here, we report an efficient, selectable marker‐free site‐specific gene insertion in maize using Agrobacterium infection. Advancements in maize transformation and new vector design enabled increase of targeted insertion frequencies by two orders of magnitude in comparison to conventional Agrobacterium‐mediated delivery. Importantly, these advancements allowed not only a significant improvement of the frequency, but also of the quality of generated events. These results further enable the application of genome editing for trait product development in a wide variety of crop species amenable to Agrobacterium‐mediated transformation.
Fluctuating thermal regimes extend longevity and maintain fecundity to increase shelf‐life of Drosophila melanogaster cultures
Authors: Melicher Dacotah , Wilson Amanda M. , Yocum George D. , Rinehart Joseph P.
Published: May 2021

Reduced temperatures increase longevity in cold‐tolerant insects, but insects that are not cold‐tolerant experience elevated mortality at constant low temperatures. Fluctuating thermal regimes (FTRs) increase longevity in many insect species while slowing or delaying development and senescence. Under FTR insects are held at low temperature with a daily warm pulse of increased temperature. The model organism Drosophila melanogaster is widely used for diverse research activities and numerous transgenic strains have been developed and must be maintained in continuous culture at stock centres. We measured the effect of FTR that oscillates between 6 and 22 °C on the longevity and fertility of adult D. melanogaster versus a constant temperature of 6 and 22 °C. We demonstrate that FTR increases mean longevity by 8.8‐fold compared to a constant 6 °C and by 5.9‐fold to a constant 22 °C. We assessed male and female fertility of FTR treated adults from 20 to 100 days at 20 day intervals and constant temperature treated adults after 7 days. Under FTR males exhibited increased fertility peaking at 80 days before dropping significantly at 100 days. Mean female fertility declined steadily under FTR but remained at 53% of constant temperature‐treated flies after 60 days. The increased male fertility remains unexplained. Fertility of the offspring of FTR‐treated adults did not differ from flies reared at constant 22 °C. FTR extends generations and cultures incubated under this protocol can establish new cultures. FTR can be used to further investigate the accumulation and mitigation of chill injury and is suitable for reducing maintenance in stock centres.
Paraptosis after ER Photodamage Initiated by m‐tetra(hydroxyphenyl) Chlorin
Authors: Kessel David
Published: May 2021

Two cell lines, A549 (human‐derived nonsmall‐cell lung cancer) and 1c1c7 (mouse hepatoma), were photosensitized with m‐THPC and irradiated under LD90 conditions. After 4 h, a pattern of cytoplasmic vacuoles had formed consistent with the initiation of paraptosis. After irradiation, there was no detectable loss of the mitochondrial membrane potential indicating no significant photodamage to mitochondria. We did, however, observe localization of m‐THPC in the endoplasmic reticulum (ER), as indicated by fluorescence microscopy. Subsequent ER perturbation is known to result in initiation of paraptosis, another pathway to cell death. While an apoptotic response to m‐THPC has been reported, the ability to target ER and induce paraptosis could explain the efficacy of this agent which could therefore eradicate cell types with an impaired apoptotic response.
Structural Engineering of Fluorescent Self‐Threaded Peptide Probes for Targeted Cell Imaging†
Authors: Schreiber Cynthia L. , Zhai Canjia , Smith Bradley D.
Published: May 2021

Squaraine figure‐eight (SF8) molecules are a new class of deep‐red fluorescent probes that are well suited for fluorescence cell microscopy due to their very high fluorescence brightness and excellent stability. Three homologous SF8 probes, with peptidyl loops that differ by very minor changes in the peptide sequence, were synthesized and assessed for probe uptake by cancer cells. One of probes included the RGD motif that is recognized by many classes of integrin receptors that reside on the surface of the cancer cells, and it permeated the cells by receptor‐mediated endocytosis. In contrast, cell microscopy showed that there was negligible cell uptake of the two homologous SF8 probes indicating differences in probe targeting capability. The synthetic method allows for easy alteration of the peptide sequence; thus, it is straightforward to develop new classes of peptidyl SF8 probes with loop sequences that target other cancer biomarkers.
Stable Transfection of the Singlet Oxygen Photosensitizing Protein SOPP3: Examining Aspects of Intracellular Behavior†
Authors: Mogensen Ditte J. , Westberg Michael , Breitenbach Thomas , Etzerodt Michael , Ogilby Peter R.
Published: May 2021

Protein‐encased chromophores that photosensitize the production of reactive oxygen species, ROS, have been the center of recent activity in studies of oxidative stress. One potential attribute of such systems is that the local environment surrounding the chromophore, and that determines the chromophore’s photophysics, ideally remains constant and independent of the global environment into which the system is placed. Therefore, a protein‐encased sensitizer localized in the mitochondria would arguably have the same photophysics as that protein‐encased sensitizer at the plasma membrane, for example. One thus obtains a useful tool to study processes modulated by spatially localized ROS. One ROS of interest is singlet oxygen, O2(a1Δg). We recently developed a singlet oxygen photosensitizing protein, SOPP, in which flavin mononucleotide, FMN, is encased in a re‐engineered light‐oxygen‐voltage protein. One goal was to ascertain how a version of this system, SOPP3, which selectively makes O2(a1Δg), in vitro, behaves in a cell. We now demonstrate that SOPP3 undergoes exacerbated irradiation‐mediated bleaching when expressed at either the plasma membrane or mitochondria in stable cell lines. We find that the environment around the SOPP3 system affects the bleaching rate, which argues against one of the key suppositions in support of a protein‐encased chromophore.
Role of Light and Plant Hormones in Stem Parasitic Plant (Cuscuta and Cassytha) Twining and Haustoria Induction
Authors: Furuhashi Katsuhisa , Iwase Koji , Furuhashi Takeshi
Published: May 2021

Cuscuta and Cassytha are two distinct stem parasitic plant genera developing haustoria at their stem. The initial step to parasitization is twining onto the host plant. Although twining is the critical first step, less attention has been paid to this aspect in stem haustoria parasitic plant studies. As tendril coiling is also controlled by light and plant hormones, we investigated the role of light (blue, red and far‐red) and hormones (auxin, brassinolide, cytokinin) in twining of stem parasitic plants (Cuscuta japonica and Cassytha filiformis). In general, both Cuscuta and Cassytha showed similar behavior to light cues. The data show that blue light is essential for twining, and a lower far‐red/red light (FR/R) ratio is important for subsequent haustoria induction. Regarding plant hormones, seedlings with solely auxin or cytokinin (iP) under blue light showed not only twining but also haustoria induction, demonstrating that auxin and iP appear to be especially important for induction. Seedlings with solely brassinolide showed no positive influence, but brassinolide together with iP caused twining even under dark conditions. This points to the presence of cross‐talk between brassinolide and cytokinin for twining.
Inventory Management Practices in Private Healthcare Facilities in Nairobi County
Authors: Karamshetty Varun , De Vries Harwin , Van Wassenhove Luk N. , Dewilde Sarah , Minnaard Warnyta , Ongarora Dennis , Abuga Kennedy , Yadav Prashant
Published: May 2021

Universal health coverage (UHC) is an integral part of the United Nations sustainable development goals. The private sector plays a prominent role in achieving UHC, being the primary source of essential medicines for many people. However, many private healthcare facilities in low‐ and middle‐income countries (LMICs) have insufficient stocks of essential medicines. Simultaneously, these same facilities carry excessive quantities of other drugs, leading to obsolescence. This suggests poor inventory control. To propose potential remedies it is vital to fully understand the underlying causes. In semi‐structured interviews with managers of private healthcare facilities in Nairobi, we asked them about their (1) inventory control systems, (2) inventory control skills, (3) time/human resource constraints, (4) budget constraints, (5) motivations for inventory control, and (6) suppliers. Our results suggest that the problems are driven by resource limitations (budget and time/human resources), managerial issues (relating to skills and systems), and market mechanisms that limit overage and underage costs. Unavailability at the supplier level and motivations for inventory control are relatively minor issues. We posit that the key causes are interlinked and stem from wider issues in the market and regulatory environment. Our results challenge prevalent beliefs about medicine supply chains in LMICs and lead to novel hypotheses. Testing these hypotheses could improve our understanding of inventory management in private healthcare facilities and aid progress in achieving UHC.
Mean–Variance Hedging for Production Planning with Multiple Products
Authors: Wang Liao
Published: May 2021

We study production planning in a multi‐product setting, in which demand for each product depends on multiple financial assets (such as commodities, market indices, etc). In addition to the production quantity decision at the beginning of the planning horizon, there is also a real‐time hedging decision throughout the horizon; and we optimize both decisions jointly. With a mean–variance problem formulation, we first derive the optimal hedging strategy, given the production quantities. This leads to an explicit objective function with which bounds on optimal production quantities are identified. Thus, optimization of the production policies can be readily solved numerically as a static minimization problem. This way, we are able to give a complete characterization of the mean–variance efficient frontier, and quantify the contribution of the hedging strategy by the variance reduction it achieves. Furthermore, the model and results are extended to allow dynamic production control that tracks the demand rates.
Supplier Encroachment with Multiple Retailers
Authors: Liu Baoshan , Guan Xu , Wang Yulan
Published: May 2021

In this study, we investigate the supplier's encroachment incentive when it distributes the product through multiple retailers. We show that the number of enrolled downstream retailers plays a pivotal role in determining the supplier's encroachment incentive and the channel members’ performances. There exists a threshold value with respect to the number of downstream retailers, below which the bright side of supplier encroachment documented in the existing literature exists; that is, encroachment can benefit not only the encroaching supplier itself but also the retailers. However, when the number of downstream retailers exceeds this threshold value, the further intensified downstream competition dampens the effect of wholesale price reduction arising from supplier encroachment. Supplier encroachment becomes always detrimental to the retailer. Moreover, with the increasing number of retailers, the supplier may become worse off when being endowed with the option of downstream encroachment, even when the supplier does not actually execute this option. We further investigate the supplier's optimal market penetration strategy when it can enroll a new retailer or open a direct channel, or it is costly to establish the indirect channel. We show that the main results remain qualitatively unchanged when the two selling channels are imperfect substitutes or retailers are asymmetric.
Financial and Operational Risk Management: Inventory Effects in the Gold Mining Industry
Authors: Markou Panos , Corsten Daniel
Published: May 2021

Financial and operational risk management are central concepts at the intersection of finance, operations, and commodity risk management. Yet, empirical evidence on their effects on inventory is lacking. We use a fine‐grained data set comprising the financial and operational risk management decisions of gold miners from 2003 to 2011 to empirically assess the effects of risk management on inventory. Faced with volatile gold prices, miners may manage (output) risk financially by committing to sell future gold production and lock in prices. They may also manage (input) costs operationally by varying the quality of ore they extract and process, thereby altering the costs they incur and influencing inventory holdings. In addition to affecting profitability, we show that these two risk management strategies have implications for inventory holdings. We find that a one‐standard deviation increase in financial risk management (FRM) is associated with an 14.3% decrease in inventory, as FRM decreases the option value of delaying processing inventory. On the other hand, a one‐standard deviation increase in operational risk management (ORM) is associated with a 3.5% increase in inventory. We also find evidence that, in this context, FRM and ORM could be viewed as complements.
Damping‐off of soybean in southern Brazil can be associated with different species of Globisporangium spp. and Pythium spp.
Authors: Molin Cleisla , Ribeiro Neucimara R. , Matsumoto Marcos N. , Fernando Giasson Nizio , Brollo Joel , Zanardo Bernardo , Pelissoni Marina , Capitanio Suélen , Comín Talia , Deuner Carolina C. , Huzar‐Novakowiski Jaqueline
Published: May 2021

Damping‐off of soybean is a common problem in some fields in southern Brazil. Frequently, Phytophthora sojae has been pointed out as the main causal agent. However, questions were raised as to whether other oomycetes could also be present. Hence, the objectives of this study were to isolate, identify, and determine the pathogenicity and aggressiveness of oomycetes isolated from soybean seedlings. Thirty‐three isolates were obtained from 13 fields. Isolates were identified based on morphology and molecular methods. Nine species were recovered: Pythium conidiophorum (n = 14, 42.4%), Globisporangium rostratifingens (n = 7, 21.2%), G. irregulare (n = 2, 6.1%), G. spinosum (n = 1, 3.0%), G. ultimum var. sporangiiferum (n = 2, 6.1%), Pythium acanthicum (n = 2, 6.1%), P. deliense (n = 1, 3.0%), P. inflatum (n = 1, 3.0%), and P. torulosum (n = 3, 9.1%). Pathogenicity and aggressiveness were determined with two soybean cultivars (DM57i52 and NEO530) in a seed rot assay and a root rot assay. All isolates were pathogenic to soybean with variable levels of aggressiveness in both assays. The range of seed disease severity index varied from 7.5 to 100 for DM57i52 and from 23.1 to 100 for NEO530. The mean root disease severity index of the soybean cultivars ranged from 29.4 to 92.8. This is the first official report of G. irregulare, G. rostratifingens, G. spinosum, G. ultimum var. sporangiiferum, P. acanthicum, P. conidiophorum, P. deliense, P. inflatum, and P. torulosum causing damping‐off of soybean in the state of Rio Grande do Sul in southern Brazil.
AlRab7 from Aeluropus lagopoides ameliorates ion toxicity in transgenic tobacco by regulating hormone signaling and reactive oxygen species homeostasis
Authors: Agarwal Parinita , Baraiya Bhagirath M. , Joshi Priyanka S. , Patel Monika , Parida Asish K. , Agarwal Pradeep K.
Published: May 2021

The plants endomembrane system of the cellular compartments with its complex membrane trafficking network facilitates transport of macromolecules. The endomembrane dynamics are essential for maintaining basic and specific cellular functions including adaptation to the extracellular environment. The plant vacuole serves as a reservoir for nutrients and toxic metabolites and performs detoxification processes to maintain cellular homeostasis. The overexpression of AlRab7, a vesicle trafficking gene from Aeluropus lagopoides, improved germination and growth and reduced ionic and oxidative stress in transgenics. Moreover, the root and shoot of transgenic tobacco showed differential accumulation of phytohormone ABA and IAA with different ionic stresses. The improved growth (root and shoot length) can be co‐related with higher IAA accumulation with NaCl stress. The low Na+/K+ ratio with different NaCl stress treatments indicates better ion homeostasis in transgenics. Furthermore, the increased stomatal density and higher number of open stomata on both leaf surfaces in transgenics during NaCl stress suggest better gaseous exchange/functioning of guard cells. The maintained or increased superoxide dismutase, catalase, ascorbate peroxidase, guaiacol peroxidase, and glutathione reductase antioxidative enzyme activities suggest that an extensive reactive oxygen species (ROS) scavenging system was triggered to detoxify cellular ROS, which remained at low levels in transgenics during the different stress treatments. Our results suggest that the AlRab7 transgenic tobacco ameliorates ionic stress by facilitating differential and selective ion transport at vacuolar membrane regulating hormone signaling, ROS homeostasis, stomatal development, and movement.
Association between swallowing disorders and cognitive disorders in adults: a systematic review and meta‐analysis
Authors: Dehaghani Shiva Ebrahimian , Doosti Afsaneh , Zare Morteza
Published: May 2021

There is no consensus regarding the association between dysphagia and cognition. The aim of this study was to quantitatively and qualitatively analyze the available evidence on the direction and strength of the association between dysphagia and cognition. PubMed, Scopus, Embase, and Web of Science were searched for studies about the association between dysphagia and cognition. A random effects model was used to determine weighted odds ratios and 95% confidence intervals. Sensitivity analysis was performed to determine the impact of each individual study on the pooled results. A total of 1427 participants showed that some cognitive disorders were significantly associated with dysphagia (odds ratio = 3.23, 95% confidence interval: 2.33–4.48). The association between cognition and swallowing disorders suggests that multiple neuroanatomical systems are involved in these two functions.
Cognitive reserve and the effects of virtual reality‐based cognitive training on elderly individuals with mild cognitive impairment and normal cognition
Authors: Kim Hyeyoung , Hong Jin Pyo , Kang Jae Myeong , Kim Won‐Hyoung , Maeng Seri , Cho Seo‐Eun , Na Kyoung‐Sae , Oh Seok Hee , Park Jung Woon , Cho Seong‐Jin , Bae Jae Nam
Published: May 2021

Background

Cognitive reserve (CR) is a concept proposed to account for discrepancies between the extent of brain pathology and clinical manifestations of that pathology. This study aimed to explore the associations between CR and the effects of cognitive training using fully immersive virtual reality (VR).

Methods

A total of 44 older adults (22 cognitively normal, 22 with mild cognitive impairment) underwent eight cognitive training sessions using VR for a period of 4 weeks. CR was assessed using the Cognitive Reserve Index questionnaire (CRIq). To evaluate baseline cognitive function and the effects of VR training, the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery was administered to all participants before and after the training.

Results

Greater improvement in the total CERAD score was seen for cognitively normal participants with higher versus lower scores on the Education subdomain of the CRIq. Among patients with mild cognitive impairment, none of the CRIq subdomain scores (Education, Working Activity, Leisure Time) were related to a change in CERAD total scores. The CRIq total score did not predict the improvement of global cognition in either group.

Conclusions

This study revealed different impacts of CR on cognitive training according to the participants' cognitive status. It also suggests that employing three proxies of CR rather than using a composite score would provide a more accurate understanding of one's CR.
Serum‐soluble PD‐L1 may be a potential diagnostic biomarker in sepsis
Authors: Sun Shaoqiong , Chen Yang , Liu Zhaojun , Tian Rui , Liu Jialin , Chen Erzhen , Mao Enqiang , Pan Tingting , Qu Hongping
Published: May 2021

To investigate whether serum‐soluble PD‐L1 (sPD‐L1) is a potential biomarker for identifying sepsis. This study enrolled 64 septic patients, 29 patients with acute appendicitis, 33 patients with acute pancreatitis and 30 healthy volunteers. Sepsis was defined according to the Sepsis 3.0 criteria.[1] The associated clinical parameters were recorded, blood samples were collected on the first day of diagnosis, and serum sPD‐L1 levels were measured using enzyme‐linked immunosorbent assays. Compared with the control group, a significant increase in sPD‐L1 levels was observed in patients with sepsis (n = 64). Increased sPD‐L1 expression correlated strongly with increased clinical inflammatory values (CRP, PCT and WBC) and decreased immunological functional parameters (CD3+, CD4+ and CD8+ cell counts). The area under the ROC curve (AUC) for sPD‐L1 in combination with the sequential organ failure assessment (SOFA) score was superior to the AUC for either sPD‐L1 or SOFA score in regard to the diagnosis of sepsis. sPD‐L1 may represent a valuable biomarker for the diagnosis of sepsis.