bluuebunny/crossref_metadata_2025_split huggingface dataset:
Designing Novel Subunit Vaccines against Herpes Simplex Virus-1 using Reverse Vaccinology Approach
Authors: Sarkar Bishajit , Ullah Md. Asad 
Published: January 2020

AbstractHerpes Simplex Virus (HSV) is an infectious virus that is responsible for various types of orofacial and genital infections. Two types of HSV viruses, HSV-1 and HSV-2, are the most dangerous HSV viruses. Every year, millions of people get infected with this menacing virus, however, no satisfactory treatment or vaccine has not yet been discovered to fight against HSV. Although there are some anti-viral therapies, however, studies have showed that such anti-viral therapies may also fail to provide good impact. In this study, a possible subunit vaccine against HSV-1, strain-17, was designed using the tools and reverse vaccinology and bioinformatics. Three potential antigenic envelope glycoproteins were selected from nine envelope glycoproteins, for possible vaccine construction. Potential epitopes capable of inducing high immunogenic response and at the same time have non-allergenicity and conservancy across other strains and species, were selected by some robust analysis, for vaccine construction. Finally, three possible vaccines were designed. Each of the vaccine construct differ from each other only in their adjuvant sequences and based on molecular docking analysis, one best vaccine construct was selected for molecular dynamics simulation study and in silico codon adaptation. The experiment showed that the selected best vaccine should be good candidate against HPV-1, strain-17. However, wet lab study should be conducted on the suggested vaccine(s) for confirming their potentiality, safety and efficacy.
Trypanosoma cruzisenses intracellular heme levels and regulates heme homeostasis by modulatingTcHTE protein expression
Authors: Pagura Lucas , Tevere Evelyn , Merli Marcelo L. , Cricco Julia A. 
Published: January 2020

ABSTRACTHeme is an essential cofactor for many biological processes in aerobic organisms. Unlike most organisms, which can synthesize itde novothrough a conserved pathway, the etiological agent of Chagas disease,Trypanosoma cruzi, as well as other trypanosomatids relevant for human health, are heme auxotrophs; thereby they must import it from the hosts.TcHTE protein is involved inT. cruziheme transport, although its specific role remains elusive. In the present work we studied endogenousTcHTE in the different life cycle stages of the parasite in order to gain insight in its function in heme transport and homeostasis. We have confirmed thatTcHTE is predominantly detected in replicative stages (epimastigote and amastigote). We have also demonstrated thatT. cruziepimastigotes can sense intracellular heme content by an unknown mechanism and regulates heme transport to adapt to changing conditions. Based on these results, we propose a model in whichT. cruzisenses intracellular heme and regulates heme transport activity adjusting the expression ofTcHTE. The elucidation and characterization of heme transport and homeostasis will contribute to a better understanding ofT. cruzibiology as well as other trypanosomatids, pointing out this pathway as a novel drug target for therapeutics.
PIE-FLIM measurements of two different FRET-based biosensor activities in the same living cells
Authors: Reissaus C.A. , Day K.H. , Mirmira R.G. , Dunn K.W. , Pavalko F.M. , Day R.N. 
Published: January 2020

ABSTRACTWe report the use of pulsed interleaved excitation-fluorescence lifetime imaging microscopy (PIE-FLIM) to measure the activities of two different biosensor probes simultaneously in single living cells. Many genetically encoded biosensors rely on the measurement of Förster resonance energy transfer (FRET) to detect changes in biosensor conformation that accompany the targeted cell signaling event. One of the most robust ways of quantifying FRET is to measure changes in the fluorescence lifetime of the donor fluorophore using fluorescence lifetime imaging microscopy (FLIM). The study of complex signaling networks in living cells demands the ability to track more than one of these cellular events at the same time. Here, we demonstrate how PIE-FLIM can separate and quantify the signals from different FRET-based biosensors to simultaneously measure changes in the activity of two cell signaling pathways in the same living cells in tissues. The imaging system described here uses selectable laser wavelengths and synchronized detection gating that can be tailored and optimized for each FRET pair. Proof-of-principle studies showing simultaneous measurement of cytosolic calcium and protein kinase A activity are shown, but the PIE-FLIM approach is broadly applicable to other signaling pathways.STATEMENT OF SIGNIFICANCEHere, we demonstrate that PIE-FLIM can separate and quantify the signals from two different FRETbased biosensors expressed in the same cells in intact tissues. PIE imaging excites the sample with two pulsed lasers of different wavelengths. The individual excitation pulses are delayed relative to one-another so that they are interleaved at the sample, and the detection channels are synchronized to the laser pulses to permit the discrete measurement of two different probe lifetimes. This enables the independent quantification of changing signals from two FRET-based biosensors. The advantage of PIE-FLIM for multiplexed imaging of FRET-based biosensor probes is that the different donor emission signals are separated in time as well as in spectral space minimizing the problem of crosstalk.
Plasticity and habitat choice match colour to function in an ambush bug
Authors: Boyle Julia , Start Denon 
Published: January 2020

Abstract

Individuals aim to maximize their fitness by matching their own phenotype to the optimum phenotype in their environment. Individuals can achieve matching through several mechanisms including habitat choice and adaptive plasticity.

A key trait of interest to biologists is colour, with background matching reciprocally camouflaging predators and prey. However, the multiple mechanisms matching an individual's colour to their background, and its consequences for function (e.g. species interactions), are rarely explored simultaneously.

Here we investigate colour variation in ambush bugs, Phymata americana, that feed on insects visiting white and yellow flowers. We conducted surveys of wild populations to establish phenotype–environment matching and its effects on prey capture, then performed habitat choice and plasticity (colour change) trials to test for the mechanisms underlying putative patterns of habitat matching.

Ambush bugs matched their background—yellower ambush bugs were found on yellow flowers and whiter ambush bugs on white flowers, and matching increased prey capture. This pattern was seemingly driven by a combination of plasticity and habitat choice.

Our study highlights how organisms can optimize trait values through a combination of plasticity and habitat choice with tangible effects on individual performance. We suggest that multiple mechanisms interactively shape phenotypes, optimizing function and fitness in the wild.

A free Plain Language Summary can be found within the Supporting Information of this article.
Language ability and adult homelessness
Authors: Pluck Graham , Barajas Brittany M. , Hernandez‐Rodriguez José L. , Martínez María A. 
Published: January 2020

AbstractBackgroundPeople experiencing homelessness are at increased risk of neurological disorder due to multiple factors such as substance abuse, infection, and higher rates of serious mental illness and traumatic brain injury. This could affect cognitive and language skills. Indeed, past research has suggested that certain language‐related skills tend to be lower in people experiencing homelessness. However, that research has compared homeless samples with age‐matched normative samples and not with samples of people from similar socio‐economic backgrounds. Therefore, it is unclear whether homelessness is even a relevant factor, or if adults who are homeless tend to have appropriate linguistic skills relative to their social and educational background.AimsTo compare the language skills of a group of adults with histories of homelessness with an education‐matched control group. It was hypothesized that participants with histories of homelessness would have worse language performance than their matched controls.Methods & ProceduresA quasi‐experimental design was employed involving 17 adults with histories of homelessness, mainly rough sleeping, in the city of Quito in Ecuador, and a sample of 16 adults who had never been homeless. All were assessed with measures of head injury, substance dependence, affective disorder and language skills. A paired‐sample analysis was performed on homeless and control participants matched for educational background, used as an index of socio‐economic background.Outcomes & ResultsThe mean years of formal education was low in both the homeless sample (mean = 5.82 years) and the control sample (mean = 6.75 years). There were no differences between the groups for any demographic or clinical factors, nor for a measure of expected or ‘premorbid’ ability based on single‐word reading, nor for current non‐verbal cognitive functioning. In contrast, the homeless group scored significantly worse than the control group on measures of auditory comprehension and oral expression.Conclusions & ImplicationsAdults with histories of homelessness may have worse language skills than would be expected based on their educational backgrounds and non‐verbal cognitive abilities. It is possible that some of this lower language ability is pathological, in the form of either a developmental language disorder or an acquired impairment. As such, some adults who are homeless may benefit from therapy directed at clinical language disorders.
The Dog that Did Not Bark: Limited Price Efficiency and Strategic Nondisclosure
Authors: ZHOU FRANK S. , ZHOU YUQING 
Published: January 2020

ABSTRACTTheory posits that investors can rationally infer the implications of strategic nondisclosure for firm value, pressuring managers to disclose information voluntarily. This study documents that the lack of an earnings guidance predicts an abnormal return of −41 basis points around the subsequent quarterly earnings announcement, suggesting that investors do not fully incorporate the implications of nonguidance. Further analyses demonstrate that limitations in price efficiency, driven by investors' limited attention and short‐selling constraints, explain the mispricing of nonguidance and are associated with less guidance issuance. Our results collectively highlight limited price efficiency as another friction when studying managers' strategic disclosure decisions.
Salvage surgery using simultaneous clamshell thoracotomy with median sternotomy for mediastinal growing teratoma syndrome
Authors: Kao Chieh‐Ni , Chou Shah‐Hwa , Huang Chien‐Lin , Lin Chih‐Hung , Chiang Hung‐Hsing , Lee Jui‐Ying , Li Hsien‐Pin , Chang Po‐Chih , Liu Yu‐Wei 
Published: January 2020

AbstractThis report describes the case of a 17‐year‐old man who developed mediastinal growing teratoma syndrome following two cycles of chemotherapy, after an initial diagnosis of primary mediastinal nonseminomatous germ cell tumor. The large, rapidly‐growing mediastinal tumor was completely resected in conjunction with right pneumonectomy, using simultaneous clamshell thoracotomy and median sternotomy. The salvage surgery with perioperative management involved in mediastinal growing teratoma syndrome is presented here.Key pointsSignificant findings of the study

The diagnosis and surgical management are challenging for patients with mediastinal growing teratoma syndrome. Nevertheless, with proper operative planning, favorable outcomes can be attained with complete resection despite the characteristic rapid growth and massive size of these neoplasms.
What this study adds
In spite of postoperative sternal dehiscence, we believe that a simultaneous clamshell thoracotomy with median sternotomy approach remains a viable option for an extremely large mediastinal growing teratoma, when tumor size prevents safe resection using other approaches due to limited visualization.
Nursing Diagnosis Risk for Delayed Surgical Recovery (00246) in Adult and Elderly: A Case‐Control Study
Authors: Rembold Simone Martins , Santana Rosimere Ferreira , de Oliveira Lopes Marcos Venicios , Melo Uyara Garcia 
Published: January 2020

PURPOSEThe study's objective was the clinical validation of the nursing diagnosis Risk for delayed surgical recovery (00246).METHODCase control study was conducted in a university hospital; the charts of 239 patient, 71 cases and 168 controls. Odds ratio was calculated for the association between each risk factor and the outcome of delayed surgical recovery.RESULTSRisk factors with higher odds of association were malnutrition, pain, and postoperative emotional response. The associated conditions were perioperative surgical site infection, psychological disorder in the postoperative period, and surgical site contamination.CONCLUSIONRisk factors have different impact on the postoperative recovery.IMPLICATIONS FOR NURSING PRACTICEKnowing the magnitude of the risk factors allows a decision making best interventions for a fast surgical recovery.
LD scores are associated with differences in allele frequencies between populations but LD score regression can still distinguish confounding from polygenicity
Authors: Alexander Mason , Curtis David 
Published: January 2020

AbstractThe linkage disequilibrium (LD) score regression method tests whether there is an association between the LD score and allele frequency differences between cases and controls. It makes the assumption that there is no association between LD score and allele frequency differences among populations and hence that any observed association is the result of a polygenic effect rather than population stratification. This assumption was previously tested only using European cohorts. In comparisons among more diverse HapMap populations, we observe that there is indeed an association between the LD score and allele frequency differences. However, this effect is small and when we carry out simulations of large case‐control samples, the effect becomes negligible. We conclude that if the intercept is small then any increase in mean chi‐squared does indeed reflect a polygenic effect rather than population stratification.
Outcomes for patients with delirium receiving hospital‐in‐the‐home treatment: An Australian perspective
Authors: Chia June , Eeles Eamonn Michael , Tattam Kym , Yerkovich Stephanie 
Published: January 2020

AbstractObjectiveTo evaluate the safety (mortality and readmissions) and efficiency (length of stay) of the hospital‐in‐the‐home delirium pathway (THDP) compared with hospital‐based care.MethodsPatients admitted to THDP were compared against an age‐matched cohort of patients with delirium managed entirely in hospital. Outcome data were obtained through retrospective chart review, and hospital coding was used to identify controls.ResultsNinety‐six patients were included in this study, of which 46 were managed on THDP. There was a significant frailty and co‐morbidity burden with no differences in the demographic profile between groups. Inpatient length of stay was shorter on THDP (THDP mean 8 days, control 11 days; P = .02). One‐month mortality was 13% in THDP compared with 24% in the control group (P = .2). One‐month readmission was 30% in THDP and 18% in the control group (P = .23).ConclusionThe hospital‐in‐the‐home delirium pathway is a promising alternative to in‐hospital delirium care for selected patients.
Genetic and pharmacological inactivation of astroglial connexin 43 differentially influences the acute response of antidepressant and anxiolytic drugs
Authors: Portal Benjamin , Delcourte Sarah , Rovera Renaud , Lejards Camille , Bullich Sebastien , Malnou Cécile E. , Haddjeri Nasser , Déglon Nicole , Guiard Bruno P. 
Published: January 2020

AbstractAimAstroglial connexins (Cxs) 30 and 43 are engaged in gap junction and hemichannel activities. Evidence suggests that these functional entities contribute to regulating neurotransmission, thereby influencing brain functions. In particular, preclinical and clinical findings highlight a role of Cx43 in animal models of depression. However, the role of these proteins in response to currently available psychotropic drugs is still unknown.MethodsTo investigate this, we evaluated the behavioural effects of the genetic and pharmacological inactivation of Cx43 on the antidepressant‐ and anxiolytic‐like activities of the selective serotonin reuptake inhibitor fluoxetine and the benzodiazepine diazepam, respectively.ResultsA single administration of fluoxetine (18 mg/kg; i.p.) produced a higher increase in hippocampal extracellular serotonin levels, and a greater antidepressant‐like effect in the tail suspension test in Cx43 knock‐down (KD) mice bred on a C57BL/6 background compared to their wild‐type littermates. Similarly, in outbred Swiss wild‐type mice, the intra‐hippocampal injection of a shRNA‐Cx43 or the acute systemic injection of the Cxs inhibitor carbenoxolone (CBX: 10 mg/kg; i.p.) potentiated the antidepressant‐like effects of fluoxetine. Evaluating the effects of such strategies on diazepam (0.5 mg/kg; i.p.), the results indicate that Cx43 KD mice or wild‐types injected with a shRNA‐Cx43 in the amygdala, but not in the hippocampus, attenuated the anxiolytic‐like effects of this benzodiazepine in the elevated plus maze. The chronic systemic administration of CBX mimicked the latter observations.ConclusionCollectively, these data pave the way to the development of potentiating strategies in the field of psychiatry based on the modulation of astroglial Cx43.
A comparison of asparaginase activity in generic formulations of E.coli derived L‐ asparaginase: In‐vitro study and retrospective analysis of asparaginase monitoring in pediatric patients with leukemia
Authors: Sankaran Hari , Sengupta Soumika , Purohit Vaitashi , Kotagere Anand , Moulik Nirmalya Roy , Prasad Maya , Dhamne Chetan , Narula Gaurav , Banavali Shripad , Gota Vikram 
Published: January 2020

AimsL‐asparaginase is an essential medicine in the treatment of pediatric acute lymphoblastic leukemia (ALL) and the quality of generic formulations is an area of concern. We compared nine generic formulations of L‐asparaginase available in India with the innovator.MethodsThe quality of formulations was assessed by measuring 72‐hour trough asparaginase activity in children with ALL during induction following administration of 10,000 IU/m2 of L‐asparaginase. In‐vitro analysis of the label claim was assessed by measuring activity of three generic formulations. Liquid chromatography‐mass spectrometry (LC/MS) was used to determine the amount of host contaminant proteins (HCPs) in the formulations.ResultsBetween March 2015 to June 2018, 240 samples from 195 patients were analyzed. The number of samples analyzed ranged from 7–66 per generic brand (median: 18) and seven of the innovator. The proportion of generic formulations that failed to achieve a predefined clinical threshold activity of 50 IU/L ranged from 16.7% (2/12) to 84.9% (28/33) in the highest activity to lowest activity generic respectively. On other hand, all innovator samples had activity greater than 50 IU/L. In‐vitro asparaginase activity in the three generic formulations tested ranged from 71.4–74.6% of the label claim (10,000 IU) compared to 93.5% for the innovator. LC/MS analysis of generic 5 identified 25 HCPs with a relative peptide count of 27.1% of the total peptides.ConclusionsGeneric formulations had lower asparaginase activity which raises serious clinical concerns regarding their quality. Until stringent regulatory enforcement improves the quality of these generics, dose adaptive strategies coupled with therapeutic drug monitoring need to be considered.
Interstitial chromosomal deletion of the tuberous sclerosis complex 2 locus is a signature for radiation‐associated renal tumors in Eker rats
Authors: Inoue Tatsuya , Kokubo Toshiaki , Daino Kazuhiro , Yanagihara Hiromi , Watanabe Fumiko , Tsuruoka Chizuru , Amasaki Yoshiko , Morioka Takamitsu , Homma‐Takeda Shino , Kobayashi Toshiyuki , Hino Okio , Shimada Yoshiya , Kakinuma Shizuko 
Published: January 2020

AbstractIonizing radiation can damage DNA and, therefore, is a risk factor for cancer. Eker rats, which carry a heterozygous germline mutation in the tumor‐suppressor gene tuberous sclerosis complex 2 (Tsc2), are susceptible to radiation‐induced renal carcinogenesis. However, the molecular mechanisms involved in Tsc2 inactivation are unclear. We subjected Fischer 344 × Eker (Long Evans Tsc2+/−) F1 hybrid rats to gamma‐irradiation (2 Gy) at gestational day 19 (GD19) or postnatal day 5 (PND5) and investigated the patterns of genomic alterations in the Tsc2 allele of renal tumors that developed at 1 year after irradiation (N = 24 tumors for GD19, N = 10 for PND5), in comparison with spontaneously developed tumors (N = 8 tumors). Gamma‐irradiation significantly increased the multiplicity of renal tumors. The frequency of LOH at the chromosome 10q12 region, including the Tsc2 locus, was 38%, 29% and 60% in renal carcinomas developed from the nonirradiated, GD19 and PND5 groups, respectively. Array comparative genomic hybridization analysis revealed that the LOH patterns on chromosome 10 in renal carcinomas were classified into chromosomal missegregation, mitotic recombination and chromosomal deletion types. LOH of the interstitial chromosomal deletion type was observed only in radiation‐associated carcinomas. Sequence analysis for the wild‐type Tsc2 allele in the LOH‐negative carcinomas identified deletions (nonirradiated: 26%; GD19: 21%) and base‐substitution mutations (GD19: 4%). Reduced expression of Tsc2 was also observed in the majority of the LOH‐negative carcinomas. Our results suggest that interstitial chromosomal deletion is a characteristic mutagenic event caused by ionizing radiation, and it may contribute to the assessment of radiation‐induced cancer risk.