bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ascending Aortic Aneurysm Secondary to Isolated Noninfectious Ascending Aortitis
Authors: Cozijnsen Luc , ter Borg Evert-Jan , Braam Richard L. , Seldenrijk Cees A. , Heijmen Robin H. , Bouma Berto J. , Merkel Peter A. 
Published: December 2018

AbstractIsolated noninfectious ascending aortitis (I-NIAA) is increasingly diagnosed at histopathologic review after resection of an ascending aortic aneurysm. PubMed was searched using the term aortitis; publications addressing the issue were reviewed, and reference lists of selected articles were also reviewed. Eleven major studies investigated the causes of an ascending aortic aneurysm or dissection requiring surgical repair: the prevalence of noninfectious aortitis ranged from 2% to 12%. Among 4 studies of lesions limited to the ascending aorta, 47% to 81% of cases with noninfectious aortitis were I-NIAA, more frequent than Takayasu arteritis or giant cell arteritis. Because of its subclinical nature and the lack of “syndromal signs” as in Takayasu arteritis or giant cell arteritis, I-NIAA is difficult to diagnose before complications occur, such as an aortic aneurysm or dissection. Therefore, surgical specimens of dissected aortic tissue should always be submitted for pathologic review. Diagnostic certainty requires the combination of a standardized histopathologic and clinical investigation. This review summarizes the current knowledge on I-NIAA, followed by a suggested approach to diagnosis, management, and follow-up. An illustrative case of an uncommon presentation is also presented. More follow-up studies on I-NIAA are needed, and diagnosis and follow-up of I-NIAA may benefit from the development of diagnostic biomarkers.
Multiple-Strain Infections of Human Cytomegalovirus with High Genomic Diversity are Common In Breast Milk from HIV-Positive Women in Zambia
Authors: Suárez Nicolás M. , Musonda Kunda G. , Escriva Eric , Njenga Margaret , Agbueze Anthony , Camiolo Salvatore , Davison Andrew J. , Gompels Ursula A. 
Published: December 2018

ABSTRACTBackgroundIn developed countries, human cytomegalovirus (HCMV) is a major pathogen in congenitally infected and immunocompromised individuals, in whom multiple-strain infection is linked to disease severity. The situation is less documente in developing countries. In Zambia, breast milk is a key route for transmitting HCMV and carries higher viral loads in HIV-positive women. We investigated HCMV strain diversity.MethodsHigh-throughput sequence datasets were generated from 28 HCMV-positive breast milk samples donated by 22 mothers (15 HIV-positive and seven HIV-negative) at 4 or 16 weeks (or both) postpartum and analysed by genotyping 12 hypervariable HCMV genes.ResultsAmong the 20 samples from 14 donors (13 HIV-positive and one HIV-negative) that yielded data meeting quality thresholds, 89 of the possible 109 genotypes were detected, and multiple-strain infections involving up to five strains per person were apparent in nine HIV-positive women. Strain diversity was extensive among individuals but conserved compartmentally and longitudinally within them. Genotypic linkage was maintained within the hypervariable UL73/UL74 and RL12/RL13/UL1 loci for virus-entry and immunomodulation, but not between genes more distant from each other.ConclusionsBreast milk from HIV-positive women contains multiple HCMV strains of high genotypic complexity and thus constitutes a major source for transmitting viral diversity.
Transcriptional Circuit Fragility Influences HIV Proviral Fate
Authors: Morton Emily L. , Forst Christian V. , Zheng Yue , De Paula-Silva Ana B. , Ramirez Nora-Guadalupe P. , Planelles Vicente , D’Orso Iván 
Published: December 2018

SUMMARYTranscriptional circuit architectures can be evolutionarily selected to precisely dictate a given response. Unlike these cellular systems, HIV is regulated through a complex circuit composed of two successive phases (host and viral), which create a positive feedback loop facilitating viral replication. However, it has long remained unclear whether both phases operate identically and to what extent the host phase influences the entire circuit. Here we report that while the host phase is regulated by a checkpoint whereby KAP1 mediates transcription activation, the virus evolved a minimalist system bypassing KAP1. Given the complex circuit’s architecture, cell-to-cell KAP1 fluctuations impart heterogeneity in the host transcriptional responses thus affecting the feedback loop. Mathematical modeling of a complete circuit reveals how these oscillations ultimately influence homogeneous reactivation potential of a latent virus. Thus, while HIV drives molecular innovation to fuel robust gene activation, it experiences transcriptional fragility thereby influencing viral fate and cure efforts.In BriefHIV evolved a minimalist but robust transcriptional circuit bypassing host regulatory checkpoints; however, the fragility of the circuit in the host phase (which primes HIV for activation) largely affects proviral transcription and fate.HighlightsThe host and viral phases of the HIV transcriptional circuit have different functional requirementsHIV evolved a minimalist program to robustly bypass host cell regulatory checkpointsA mathematical model reveals that the host phase is subject to transcriptional circuit fragilityHost transcriptional circuit fragility influences the viral feedback and latency reversal potential
A non-catalytic function of carbonic anhydrase IX contributes to the glycolytic phenotype and pH regulation in human breast cancer cells
Authors: Mboge Mam Y. , Chen Zhijuan , Khokhar Daniel , Wolff Alyssa , Ai Lingbao , Heldermon Coy D. , Bozdag Murat , Carta Fabrizio , Supuran Claudiu T. , Brown Kevin D. , McKenna Robert , Frost Christopher J. , Frost Susan C. 
Published: December 2018

ABSTRACTThe most aggressive and invasive tumor cells often reside in hypoxic microenvironments and rely heavily on rapid anaerobic glycolysis for energy production. This switch from oxidative phosphorylation to glycolysis, along with up-regulation of the glucose transport system, significantly increases the release of lactic acid from cells into the tumor microenvironment. Excess lactate and proton excretion exacerbate extracellular acidification to which cancer cells, but not normal cells, adapt. We have hypothesized that carbonic anhydrases (CAs) play a role in stabilizing both intracellular and extracellular pH to favor cancer progression and metastasis. Here we show that proton efflux (acidification) using the glycolytic rate assay is dependent on both extracellular pH (pHe) and CA IX expression. Yet, isoform selective sulfonamide-based inhibitors of CA IX did not alter proton flux, which suggests that the catalytic activity of CA IX is not necessary for this regulation. Other investigators have suggested the CA IX cooperates with the MCT transport family to excrete protons. To test this possibility, we examined the expression patterns of selected ion transporters and show that members of this family are differentially expressed within the molecular subtypes of breast cancer. The most aggressive form of breast cancer, triple negative breast cancer (TNBC), appears to coordinately express the monocarboxylate transporter 4 (MCT4) and carbonic anhydrase IX (CA IX). This supports a possible mechanism that utilizes the intramolecular H+shuttle system in CA IX to facilitate proton efflux through MCT4.
Determining the link between alpha-gal-containing antigens in North American ticks and red meat allergy
Authors: Crispell Gary , Commins Scott P. , Archer-Hartman Stephanie A. , Choudhary Shailesh , Dharmarajan Guha , Azadi Parastoo , Karim Shahid 
Published: December 2018

AbstractDevelopment of specific IgE antibodies to the oligosaccharide galactose-α-1, 3-galactose (α-gal) following tick bites has been shown to be the source of red meat allergy. In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteome, carbohydrate analysis, and basophil activation approaches. Using anti-α-gal antibodies, α-gal was identified in the salivary glands of bothAm. americanumandIx. scapularis, whileAm. maculatumandDe. variabilisappeared to lack the sugar. PNGase F treatment confirmed the deglycosylation of N-linked α-gal-containing proteins in tick salivary glands. Immunolocalization of α-gal moieties to the salivary secretory vesicles of the salivary acini also confirmed the secretory nature of α-gal-containing antigens in ticks.Am. americanumticks were fed human blood (lacks α-gal) using an artificial membrane feeding system to determine the source of α-gal. N-linked glycan analysis revealed thatAm. americanumandIx. scapularishave α-gal in their saliva and salivary glands, butAm. maculatumcontains no detectable quantity. Salivary samples fromAm. americanumandIx. scapularisstimulated activation of basophils primed with plasma from α-gal allergic subjects. Together, our data support the idea that bites from certain tick species may specifically create a risk for the development of α-gal-specific IgE and hypersensitivity reactions in humans. Alpha-Gal syndrome challenges the current food allergy paradigm and broadens opportunities for future research.
Latitudinal and seasonal variation in space use by a large, predatory reef fish,Plectropomus leopardus
Authors: Scott Molly E. , Heupel Michelle R. , Simpfendorfer Colin A. , Matley Jordan K. , Pratchett Morgan S. 
Published: December 2018

AbstractTemperature directly affects the metabolic rate and resource requirements of ectothermic animals, which is likely to influence their movement and habitat use. Space use is a fundamental component of an animal’s ecology, and the extent of an animal’s home range has consequences for individual distributions, community structure and ecosystem function. As ocean temperatures continue to rise as a result of global warming, determining the effects of temperature on space use and movement patterns of important fisheries species is vital.Our aim was to investigate the spatial and temporal variation in space use by a tropical fisheries species, the leopard coralgrouper (Plectropomus leopardus), from two latitudinally distinct locations on Australia’s Great Barrier Reef to determine the potential response of large‐bodied tropical fishes to ocean warming through behavioural modification.Using passive acoustic telemetry of 36 tagged individuals, we found that both core use areas (50%KUD) and home range extent (95%KUD) varied with respect to location, season, body size and temperature. Average home range extent (95%KUD) for taggedP. leoparduswas 0.32 km2at the high‐latitude location (Heron Island) compared to 0.23 km2at the low‐latitude location (Opal Reef). However, core use areas (50%KUD) did not differ significantly between the two locations.Seasonal differences were also apparent at both locations withP. leopardusshowing contraction in home range extent during the summertime. This effect was most pronounced at the low‐latitude location where home range was significantly reduced during summer when temperatures exceeded 27°C.Taken together, our findings indicate that higher ambient temperature may elicit a sustained and significant decline in space use by a commercially important reef fish. Given projected increases in ocean temperature due to global climate change, large‐bodied reef fishes may be increasingly constrained in their movement and space use, which will have ramifications for individual fitness, population viability, fisheries productivity and ecological function.Aplain language summaryis available for this article.
Inefficiency of manual weeding in rainfed rice systems affected by parasitic weeds
Authors: N'cho Simon Akahoua , Mourits Monique , Rodenburg Jonne , Oude Lansink Alfons 
Published: December 2018

AbstractManual weeding is the predominant weed control practice and the most labor‐consuming activity in smallholder, rainfed rice systems in sub‐Saharan Africa. This study investigates the technical inefficiency of weeding labor, other labor, and overall inputs, and identifies sources of technical inefficiency of weeding labor in the context of parasitic weed infestation. The analysis applies a two‐stage approach. First, a directional input distance function DEA approach was used to compute input‐specific technical inefficiencies. Second, sources of technical inefficiency of weeding labor were identified using a truncated bootstrap regression. Data from 406 randomly selected smallholder farmers from Benin (n = 215) and Côte d'Ivoire (n = 191) were used. The technical inefficiency of weeding labor was high in both countries (58% in Côte d'Ivoire and 69% in Benin). This implies that a substantial fraction of weeding labor could be saved without reducing rice productivity or increasing the use of other inputs. A decrease in the technical inefficiency of weeding labor with an increase in production scale was observed. In addition, weeding regime and education level were each associated to significant changes in the technical inefficiency of weeding labor.
Novel 3D in vitro models to evaluate trophoblast migration and invasion
Authors: You Yuan , Stelzl Patrick , Zhang Yonghong , Porter James , Liu Hong , Liao Ai‐Hua , Aldo Paulomi B. , Mor Gil 
Published: December 2018

ProblemEmbryo implantation depends on the interactions between the developing embryo and the maternal endometrium. Signals originating from the decidua play a critical role in the process of implantation and trophoblast invasion; however, the molecular mechanisms mediating this interaction are poorly understood. The objective of this study was to develop in vitro models that would mimic the processes of attachment, migration, and early invasion of the trophoblast.Methods of studyFirst trimester trophoblast cells (Sw.71 cells) were cultured in low attachment plates to form blastocyst‐like spheroids (BLS). Epithelial‐mesenchymal transition (EMT) characterization during BLS formation was determined by RT‐PCR and Western Blot. The two 3D in vitro culture models consist of (a) trophoblast migration: BLS cultured in suspension (b) trophoblast invasion: human endometrium stromal cells (HESC) plated in the bottom of a 96‐well plate, covered by Matrigel and BLS transferred on top. Matrigel was used to mimic the human endometrial extracellular matrix.ResultsUsing 3D cell culture systems and real‐time imaging, we are able to determine the impact of endometrial factors on trophoblast cell function. Endometrial stromal cells promote blastocyst‐like spheroid migration of trophoblast cells and invasion of the extracellular matrix.ConclusionWe report the characterization of 3D in vitro models to evaluate the interaction between endometrial cells and trophoblast during the process of migration and invasion. The models are useful tools in order to further study the molecular mechanism of embryo‐maternal uterine cells interactions.
Effect of preoperative detrusor underactivity on long‐term surgical outcomes of photovaporization and holmium laser enucleation in men with benign prostatic hyperplasia: a lesson from 5‐year serial follow‐up data
Authors: Cho Min Chul , Yoo Sangjun , Park Juhyun , Cho Sung Yong , Son Hwancheol , Oh Seung‐June , Paick Jae‐Seung 
Published: December 2018

ObjectivesTo investigate the impact of preoperative detrusor underactivity (DU) on serial treatment outcomes over the course of 5 years after photovaporization (PV) or holmium laser enucleation (HoLEP) in patients with benign prostatic hyperplasia (BPH), to compare its impact after PV vs HoLEP, and to identify predictors of long‐term lower urinary tract symptoms (LUTS) improvement.Materials and MethodsThis study involved 245 patients with BPH who had complete 5‐year follow‐up data (PV using 120W‐HPS, n = 143, HoLEP, n = 102), grouped as follows: PV‐HPS‐DU(+), n = 114; PV‐HPS‐DU(−), n = 29; HoLEP‐DU(+), n = 56; and HoLEP‐DU(−), n = 46. Bladder contractility index (BCI) < 100 was regarded as DU. Serial treatment outcomes for the International Prostate Symptom Score (IPSS) questionnaire, uroflowmetry and serum PSA level at 6 months, and at 1, 2, 3, 4 and 5 years after surgery, were compared among the groups. LUTS improvement was defined as a reduction in total IPSS of ≥50% relative to baseline.ResultsImprovement in total IPSS, quality of life (QoL) index and post‐void residual urine volume (PVR) in the PV‐HPS‐DU(+) and PV‐HPS‐DU(−) groups were maintained up to 5 years after PV, except for maximum urinary flow rate (Qmax) and bladder voiding efficiency. In the HoLEP‐DU(+) and HoLEP‐DU(−) groups, improvements in all outcome variables were maintained up to 5 years after HoLEP. Deteriorations in subtotal voiding symptom score, total IPSS and Qmax with time during the long‐term period after surgery were more pronounced in the PV‐HPS‐DU(+) and HoLEP‐DU(+) groups than in the PV‐HPS‐DU(−) and HoLEP‐DU(−) groups. Reductions in subtotal voiding symptom score, total IPSS, QoL index, and serum PSA were greater in the HoLEP‐DU(+) group than in the PV‐HPS‐DU(+) group throughout follow‐up. The type of surgery (HoLEP vs PV) and higher baseline BCI were independent predictors of LUTS improvement at 5 years after surgery.ConclusionGenerally, improvement of micturition symptoms, QoL and PVR in patients with DU appears to be maintained up to 5 years after PV or HoLEP. Deterioration of voiding symptoms and urinary flow rate at long‐term follow‐up visits after PV or HoLEP was more pronounced in patients with LUTS/BPH with DU than in those without DU. Patients with BPH with DU may benefit from more complete removal of prostatic adenoma by HoLEP and greater baseline bladder contractility in terms of micturition symptoms and QoL.
Degeneration of dopaminergic circuitry influences depressive symptoms in Lewy body disorders
Authors: Patterson Lina , Rushton Steven P. , Attems Johannes , Thomas Alan J. , Morris Christopher M. 
Published: December 2018

Abstract

Aims
Depression is commonly observed even in prodromal stages of Lewy body disorders (LBD), and is associated with cognitive impairment and a faster rate of cognitive decline. Given the role of dopamine in the development of movement disorders, but also in motivation and reward, we investigated neurodegenerative pathology in dopaminergic circuitry in Parkinson's disease (PD), PD with dementia (PDD) and dementia with Lewy bodies (DLB) patients in relation to depressive symptoms.
Methods
α‐synuclein, hyperphosphorylated tau and amyloid‐beta pathology was assessed in 17 DLB, 14 PDD and 8 PD cases within striatal and midbrain subregions, with neuronal cell density assessed in substantia nigra and ventral tegmental area. Additionally, we used a structural equation modeling (SEM) approach to investigate the extent to which brain connectivity might influence the deposition of pathological proteins within dopaminergic pathways.
Results
A significantly higher α‐synuclein burden was observed in the substantia nigra (P = 0.006), ventral tegmental area (P = 0.011) and nucleus accumbens (P = 0.031) in LBD patients with depression. Significant negative correlations were observed between cell density in substantia nigra with Lewy body (LB) Braak stage (P = 0.013), whereas cell density in ventral tegmental area showed negative correlations with LB Braak stage (P = 0.026) and neurofibrillary tangle Braak stage (P = 0.007).
Conclusions
Dopaminergic α‐synuclein pathology appears to drive depression. Selective targeting of dopaminergic pathways may therefore provide symptomatic relief for depressive symptoms in LBD patients.
Significant differences in T cell receptor repertoires in lung adenocarcinomas with and without epidermal growth factor receptor mutations
Authors: Miyauchi Eisaku , Matsuda Tatsuo , Kiyotani Kazuma , Low Siew‐Kee , Hsu Yu‐Wen , Tsukita Yoko , Ichinose Masakazu , Sakurada Akira , Okada Yoshinori , Saito Ryoko , Nakamura Yusuke 
Published: December 2018

Recent clinical trials of non‐small cell lung cancer with immune checkpoint inhibitors revealed that patients with epidermal growth factor receptor (EGFR) mutations had more unfavorable outcomes compared with those with wild‐type EGFR. However, the underlying mechanism for the link between EGFR mutations and immune resistance remains unclear. We performed T cell receptor (TCR) repertoire analysis of resected lung adenocarcinoma tissues with and without EGFR mutations to investigate the characteristics of TCR repertoires. We collected a total of 39 paired (normal and tumor) lung tissue samples (20 had EGFR mutations) and conducted TCR repertoire analysis as well as whole‐exome sequencing (WES) and transcriptome analysis. The TCR diversity index in EGFR‐mutant tumors was significantly higher than that in EGFR‐wild‐type tumors (median [range] 552 [162‐1,135] vs 230 [30‐764]; P < .01), suggesting higher T cell clonal expansion in EGFR‐wild‐type tumors than in EGFR‐mutant tumors. In WES, EGFR‐mutant tumors showed lower numbers of non‐synonymous mutations and predicted neoantigens than EGFR‐wild‐type tumors (P < .01, P = .03, respectively). The number of non‐synonymous mutations revealed a positive correlation with the sum of frequencies of the TCRβ clonotypes of 1% or higher in tumors (r = .52, P = .04). The present study demonstrates significant differences in TCR repertoires and the number of predicted neoantigens between EGFR‐mutant and wild‐type lung tumors. Our findings provide important information for understanding the molecular mechanism behind EGFR‐mutant patients showing unfavorable responses to immune checkpoint inhibitors.
Noteworthy effect of slight variation in aliphatic chain length of trisubstituted imidazole inhibitors against epidermal growth factor receptor L858R/T790M/C797S mutant in cancer therapy
Authors: Akher Farideh Badichi , Farrokhzadeh Abdolkarim , Soliman Mahmoud E. S. 
Published: December 2018

Abstract11h is a very potent inhibitor against epidermal growth factor receptor triple mutation L858R/T790M/C797S (EGFRTM) with 13‐fold stronger potency than the FDA‐approved osimertinib. Recently, two new EGFRTM inhibitors, 11d and 11e, were reported which revealed 2.8‐ and 2.3‐fold stronger potency than 11h, respectively. 11h, 11d, and 11e have the same structures but differ only in their aliphatic chain length. However, the exact effects of differential aliphatic chain length on the inhibitory potencies of these compounds require further elaboration at the atomistic level, hence the objective of this report. Various computational tools were employed for this purpose. From our findings, it was revealed that van der Waals (vdW) interactions modulate the binding mechanisms of these inhibitors and play the most important role in the differential inhibitory activities of 11d, 11h, and 11e. The strong hydrogen bond formation between the aliphatic chain of 11d and key residue ARG841 was recognized as the reason for its higher activity and inhibitory potency relative to 11h and 11e. Moreover, the extension of the N‐terminal loop into the active site for vdW interaction with the phenyl group of 11e and carbon–hydrogen bond formed between the aliphatic chain of 11e and LEU718 engendered a higher activity of 11e than 11h.