bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparative analysis of unintegrated HIV-1 DNA measurement as a potential biomarker of the cellular reservoir in the blood of patients controlling and non-controlling viral replication
Authors: Orlandi Chiara , Canovari Benedetta , Bozzano Federica , Marras Francesco , Pasquini Zeno , Barchiesi Francesco , De Maria Andrea , Magnani Mauro , Casabianca Anna
Published: May 2020

Background

The persistence of HIV-1 in reservoir cells is one of the major obstacles to eradicating the virus in infected individuals receiving combination antiretroviral therapy (ART). HIV-1 persists in infected cells as a stable integrated genome and more labile unintegrated DNA (uDNA), which includes linear, 1-LTR and 2-LTR circular DNA. 2-LTR circle DNA, although less abundant, is considered a surrogate marker of recent infection events and is currently used instead of the other unintegrated species as a diagnostic tool. This pilot study aimed to investigate how to best achieve the measurement of uDNA.

Methods

A comparative analysis of two qPCR-based methods (U-assay and 2-LTR assay) was performed on the blood of 12 ART-naïve, 14 viremic and 29 aviremic On-ART patients and 20 untreated spontaneous controllers (HIC), sampled at a single time point.

Results

The U-assay, which quantified all unintegrated DNA species, showed greater sensitivity than the 2-LTR assay (up to 75%, p < 0.0001), especially in viremic subjects, in whom other forms, in addition to 2-LTR circles, may also accumulate due to active viral replication. Indeed, in aviremic On-ART samples, the U-assay unexpectedly measured uDNA in a higher proportion of samples (76%, 22/29) than the 2-LTR assay (41%, 12/29), (p = 0.0164). A trend towards lower uDNA levels was observed in aviremic vs viremic On-ART patients, reaching significance when we combined aviremic On-ART and HIC (controllers) vs Off-ART and viremic On-ART subjects (non-controllers) (p = 0.0003), whereas 2-LTR circle levels remained constant (p ≥ 0.2174). These data were supported by the high correlation found between uDNA and total DNA (r = 0.69, p < 0.001).

Conclusions

The great advantage of the U-assay is that, unlike the 2-LTR assay, it allows the accurate evaluation of the totality of uDNA that can still be measured even during successful ART when plasma viremia is below the cut-off of common clinical tests (< 50 copies/mL) and 2-LTR circles are more likely to be under the quantification limit. UDNA measurement in blood cells may be used as a biomarker to reveal a so far hidden or underestimated viral reservoir. The potential clinical relevance of uDNA quantification may lead to improvements in diagnostic methods to support clinical strategies.
Non-active site mutants of HIV-1 protease influence resistance and sensitisation towards protease inhibitors
Authors: Bastys Tomas , Gapsys Vytautas , Walter Hauke , Heger Eva , Doncheva Nadezhda T. , Kaiser Rolf , de Groot Bert L. , Kalinina Olga V.
Published: May 2020

Background

HIV-1 can develop resistance to antiretroviral drugs, mainly through mutations within the target regions of the drugs. In HIV-1 protease, a majority of resistance-associated mutations that develop in response to therapy with protease inhibitors are found in the protease’s active site that serves also as a binding pocket for the protease inhibitors, thus directly impacting the protease-inhibitor interactions. Some resistance-associated mutations, however, are found in more distant regions, and the exact mechanisms how these mutations affect protease-inhibitor interactions are unclear. Furthermore, some of these mutations, e.g. N88S and L76V, do not only induce resistance to the currently administered drugs, but contrarily induce sensitivity towards other drugs. In this study, mutations N88S and L76V, along with three other resistance-associated mutations, M46I, I50L, and I84V, are analysed by means of molecular dynamics simulations to investigate their role in complexes of the protease with different inhibitors and in different background sequence contexts.

Results

Using these simulations for alchemical calculations to estimate the effects of mutations M46I, I50L, I84V, N88S, and L76V on binding free energies shows they are in general in line with the mutations’ effect on $$IC_{50}$$IC50 values. For the primary mutation L76V, however, the presence of a background mutation M46I in our analysis influences whether the unfavourable effect of L76V on inhibitor binding is sufficient to outweigh the accompanying reduction in catalytic activity of the protease. Finally, we show that L76V and N88S changes the hydrogen bond stability of these residues with residues D30/K45 and D30/T31/T74, respectively.

Conclusions

We demonstrate that estimating the effect of both binding pocket and distant mutations on inhibitor binding free energy using alchemical calculations can reproduce their effect on the experimentally measured $$IC_{50}$$IC50 values. We show that distant site mutations L76V and N88S affect the hydrogen bond network in the protease’s active site, which offers an explanation for the indirect effect of these mutations on inhibitor binding. This work thus provides valuable insights on interplay between primary and background mutations and mechanisms how they affect inhibitor binding.
Generation and validation of a highly sensitive bioluminescent HIV-1 reporter vector that simplifies measurement of virus release
Authors: Kirui James , Freed Eric O.
Published: May 2020

Background

The continued persistence of HIV-1 as a public health concern due to the lack of a cure calls for the development of new tools for studying replication of the virus. Here, we used NanoLuc, a small and extremely bright luciferase protein, to develop an HIV-1 bioluminescent reporter virus that simplifies functional measurement of virus particle production.

Results

The reporter virus encodes a Gag protein containing NanoLuc inserted between the matrix (MA) and capsid (CA) domains of Gag, thereby generating virus particles that package high levels of the NanoLuc reporter. We observe that inserting the NanoLuc protein within HIV-1 Gag has minimal impact on Gag expression and virus particle release. We show that the reporter virus recapitulates inhibition of HIV-1 particle release by Gag mutations, the restriction factor tetherin, and the small-molecule inhibitor amphotericin-B methyl ester.

Conclusion

These results demonstrate that this vector will provide a simple and rapid tool for functional studies of virus particle assembly and release and high-throughput screening for cellular factors and small molecules that promote or inhibit HIV-1 particle production.
Functional movement assessment by means of inertial sensor technology to discriminate between movement behaviour of healthy controls and persons with knee osteoarthritis
Authors: van der Straaten Rob , Wesseling Mariska , Jonkers Ilse , Vanwanseele Benedicte , Bruijnes Amber K. B. D. , Malcorps Jan , Bellemans Johan , Truijen Jan , De Baets Liesbet , Timmermans Annick
Published: May 2020

Background

Apart from biomechanical alterations in movement patterns, it is known that movement limitations in persons with knee osteoarthritis (PwKOA) are related to an individual’s perception and belief regarding pain and disability. To gain more insights into the functional movement behaviour of PwKOA in a clinical setting, inertial sensor technology can be applied. This study first aims to evaluate the ability of inertial sensors to discriminate between healthy controls (HC) and PwKOA. Secondly, this study aims to determine the relationship between movement behaviour, pain-related factors and disability scores.

Methods

Twelve HC and 19 PwKOA were included. Five repetitions of six functional movement tasks (walking, forward lunge, sideward lunge, ascent and descent stairs, single leg squat and sit-to-stand) were simultaneously recorded by the inertial sensor system and a camera-based motion analysis system. Statistically significant differences in angular waveforms of the trunk, pelvis and lower limb joints between HC and PwKOA were determined using one-dimensional statistical parametric mapping (SPM1D). The Knee injury and Osteoarthritis Outcome Score and TAMPA scale for Kinesiophobia were used to evaluate the relationship between discriminating joint motion, pain-related factors and disability using spearman’s correlation coefficients.

Results

PwKOA had significantly less trunk rotation, internal pelvis rotation and knee flexion ROM during walking. Additionally, the reduced knee flexion (i.e. at the end of the stance phase and swing phase) was related to increased level of perceived pain. During the sideward lunge, PwKOA had significantly less knee flexion, ankle plantarflexion and hip abduction. This decreased hip abduction (i.e. during stance) was related to higher fear of movement. Finally, PwKOA had significantly less knee flexion during the forward lunge, single leg squat and during ascent and descent stairs. No significant correlations were observed with disability.

Conclusions

Inertial sensors were able to discriminate between movement characteristics of PwKOA and HC. Additionally, significant relationships were found between joint motion, perceived pain and fear of movement. Since inertial sensors can be used outside the laboratory setting, these results are promising as they indicate the ability to evaluate movement deviations. Further research is required to enable measurements of small movement deviations in clinically relevant tasks.
ALK-1-positive inflammatory myofibroblastic tumor of the thyroid complicated by Hashimoto’s thyroiditis: report of a rare case and a literature review
Authors: Li Cheng-fang , Wu Xing-long , Wang Jin-jing , Wang Kai , Zhang Su-yuan , Huang Jia-jia , Hu Han-zhong , Zheng Hong
Published: May 2020

Background

Inflammatory myofibroblastic tumors (IMTs) of the thyroid are extremely rare soft-tissue tumors. In the literature, IMTs are sometimes called plasma cell granulomas (PCGs) or inflammatory pseudotumors, which often causes ambiguity. To date, 17 cases of PCGs and five cases of thyroid IMTs have been reported. These cases reveal that IMTs of the thyroid are often negative for the anaplastic lymphoma kinase (ALK-1) gene. To provide further information on this rare lesion, we present a case of an ALK-1-positive thyroid IMT and a review of IMTs of the thyroid.

Case presentation

A 34-year-old Chinese woman presented with a painless neck mass that had persisted for over a month. Ultrasonography revealed a 4.28 × 2.53 cm2hypoechoic mass, in the left lobe of the thyroid gland. Serum levels of thyroglobulin and anti-thyroglobulin antibodies were high. Subsequently, left lobectomy was performed. Macroscopically, the lesion was a gray-brown nodular mass with a partial envelope. Histologically, two different lesion types were observed. The first lesion showed classic spindle cell proliferation, with spindle cells arranged in fascicles, accompanied by mature inflammatory cells. The other lesion showed a large number of infiltrating lymphocytes, with lymphoid follicles in the remaining thyroid gland, which was atrophic. Immunohistochemical staining showed that the spindle cells were negative for CK19, CyclinD1, Gelectin-3, EMA, CD34, S100, Bcl-2, and STAT-6, but strongly positive for ALK-1, vimentin, and TTF1. CK was focally expressed, and the Ki-67 index was 5%. A diagnosis of IMT was proposed according to immunohistochemical findings and morphology. Hashimoto’s thyroiditis was confirmed according to serum levels of thyroglobulin and anti-thyroglobulin antibodies and morphology. The patient did not receive adjuvant therapy. She remained alive without disease recurrence for 10 months after lobectomy.

Conclusions

IMTs should be considered in the diagnosis when spindle cell proliferation accompanied by mature inflammatory cells is observed, spindle cells are mildly atypical, and myofibroblast differentiation is present in the thyroid. A uniform diagnostic term is crucial to avoid ambiguity. Clinicians and pathologists should be aware of the necessity for long-term follow-up, especially in ALK-positive cases. The therapeutic potential of ALK-1 positivity should be explored further.
Foetal neural progenitors contribute to postnatal circuits formation ex vivo: an electrophysiological investigation
Authors: Manzati Matteo , Sorbo Teresa , Giugliano Michele , Ballerini Laura
Published: May 2020

Neuronal progenitor cells (NPC) play an essential role in homeostasis of the central nervous system (CNS). Considering their ability to differentiate into specific lineages, their manipulation and control could have a major therapeutic impact for those CNS injuries or degenerative diseases characterized by neuronal cell loss. In this work, we established an in vitro co-culture and tested the ability of foetal NPC (fNPC) to integrate among post-mitotic hippocampal neurons and contribute to the electrical activity of the resulting networks. We performed extracellular electrophysiological recordings of the activity of neuronal networks and compared the properties of spontaneous spiking in hippocampal control cultures (HCC), fNPC, and mixed circuitries ex vivo. We further employed patch-clamp intracellular recordings to examine single-cell excitability. We report of the capability of fNPC to mature when combined to hippocampal neurons, shaping the profile of network activity, a result suggestive of newly formed connectivity ex vivo.
Allogeneic stem cell transplantation for peripheral T cell lymphomas: a retrospective study in 285 patients from the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC)
Authors: Mamez Anne-Claire , Dupont Axelle , Blaise Didier , Chevallier Patrice , Forcade Edouard , Ceballos Patrice , Mohty Mohamad , Suarez Felipe , Beguin Yves , Peffault De Latour Regis , Rubio Marie-Thérèse , Tournilhac Olivier , Nguyen Stéphanie
Published: May 2020

Background

Peripheral T cell lymphomas form a heterogeneous group with a usually dismal prognostic. The place of allogeneic stem cell transplantation to treat PTCL is debated.

Methods

We retrospectively analyzed the overall survival (OS), event-free survival (EFS), relapse, and transplant-related mortality (TRM) and associated variables in 285 adults with non-primary cutaneous PTCL (PCTL-NOS (39%), angioimmunoblastic T cell lymphomas (29%), anaplastic T cell lymphomas (15%), and other subtypes (17%)), who received alloSCT in 34 centers between 2006 and 2014.

Results

AlloSCT was given as part of front-line therapy (n= 138) to 93 patients in first complete response (CR) and 45 in first partial response (PR), and of salvage therapy (n= 147) to 116 patients for second or more CR/PR and 31 for progressive disease. Reduced-intensity conditioning (RIC) was given to 172 patients (62%), while 107 (38%) received myeloablative conditioning (MAC). The median follow-up was 72.4 months. The 2- and 4-year OS were 65% and 59%, respectively, and the cumulative incidence of relapse was 18% after 1 year and 19% after 2 years. TRM was 21% at 1 year, 24% after 2 years, and 28% after 4 years. In multivariate analysis, grade III–IV acute GvHD (HR = 2.57, 95% CI 1.53–4.31;p= 0.00036), low Karnofsky score < 80% (HR = 5.14, 95% CI 2.02–13.06;p= 0.00058), and progressive disease status before transplant (HR = 2.21, 95% CI 1.25–3.89;p =0.0062) were significantly associated with a reduced OS.

Conclusions

The data demonstrate in the largest retrospective cohort of non-cutaneous PTCL so far reported that alloSCT after RIC or MAC is an effective strategy, even in chemoresistant patients.
The tibialis posterior tendon footprint: an anatomical dissection study
Authors: Willegger Madeleine , Seyidova Nargiz , Schuh Reinhard , Windhager Reinhard , Hirtler Lena
Published: May 2020

Background

The tibialis posterior tendon (TPT) is the main dynamic stabilizer of the medial longitudinal arch of the foot. Especially in adult acquired flatfoot deformity (AAFD) the TPT plays a detrimental role. The pathology and function of the tendon have been extensively investigated, but knowledge of its insertional anatomy is paramount for surgical procedures. This study aimed to analyze the complex distal footprint anatomy of the TPT.

Methods

Forty‐one human anatomical specimens were dissected and the distal TPT was followed to its bony footprints. After tendon removal the footprints were marked with ink. Standardized photographs were taken and consecutively analyzed by digital imaging measurements. Footprint length, width, area of insertion, location, and shape was studied regarding the main insertion at the navicular bone.

Results

All specimens had the main TPT insertion at the navicular bone (41/41, 100%). Sixty‐three percent of navicular TPT insertions were located at the plantar aspect. The mean navicular footprint measured 12.1 mm × 6.9 mm in length and width, respectively. The tendon further spread into several slips which anchored the tibialis posterior deep in the plantar arch. TPT insertions were highly variable with an involvement of up to eight distinct bony footprints in the mid‐ and hindfoot. The second most common additional footprint was the lateral cuneiform (93% of dissected feet), followed by the medial cuneiform (80%), the metatarsal bases [1–5] (80%), the cuboid (46%), the intermediate cuneiform (19%), and the calcaneus (12%).

Conclusions

The present study adds to current knowledge on the footprint anatomy of the TPT. Based on the findings of this study we advocate a plantar location of flexor digitorum longus tendon transfer in flexible AAFD in order to restore the anatomical lever and insertion of the TPT.
Identified plasma proteins related to vascular structure are associated with coarctation of the aorta in children
Authors: Ma Siyu , Zheng Junqiang , Xu Yang , Yang Zhaocong , Zhu Yu , Su Xiaoqi , Mo Xuming
Published: May 2020

Background

Coarctation of the aorta (CoA), presenting with local stenosis of the aorta is involved in many cardiovascular processes. However, there has been little research on the mechanism of coarctation of the aorta.

Methods

Altered proteins were identified by isobaric tag for relative and absolute quantitation (iTRAQ) technology in 8 participants, and further analysed by heatmap, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) and Search Tool for the Retrieval of Interacting Gene (STRING). Of these, two vascular structure-related proteins were further validated by using enzyme-linked immunosorbent assay (ELISA) in a new cohort of CoA patients.

Results

39 differentially expressed plasma proteins were first identified in patients with coarctation of the aorta by iTRAQ. Of these, fibulin-1 (FBLN1) and insulin-like growth factor-binding protein complex acid labile subunit (ALS) were considered candidates and further validation also showed that the level of FBLN1 in the CoA group (8.92 ± 2.36 μg/ml) was significantly higher compared with control group (6.13 ± 1.94 μg/ml), and the level of ALS in CoA children (348.08 ± 216.74 ng/ml) was significantly lower than the level in normal children (619.46 ± 274.08 ng/ml).

Conclusions

The differentially expressed proteins identified in the plasma from CoA patients indicated that they may play critical roles in CoA and that they could potentially be utilized as biomarkers for diagnosis. Altered vascular related proteins were associated with COA. These results provide a foundation for further understanding and studying the aetiology and pathogenesis of coarctation of the aorta.
Equid infective Theileria cluster in distinct 18S rRNA gene clades comprising multiple taxa with unusually broad mammalian host ranges
Authors: Bishop Richard P. , Kappmeyer Lowell S. , Onzere Cynthia K. , Odongo David O. , Githaka Naftaly , Sears Kelly P. , Knowles Donald P. , Fry Lindsay M.
Published: May 2020

Equine theileriosis, a tick-transmitted disease caused by the hemoprotozoan parasites Theileria equi and Theileria haneyi, affects equids throughout tropical and subtropical regions of the world. It is a significant regulatory concern in non-endemic countries, where testing for equine theileriosis is required prior to horse import to prevent parasite entry. Within endemic areas, infection causes significant morbidity and mortality, leading to economic losses. No vaccine for equine theileriosis is available, and current drug treatment protocols are inconsistent and associated with significant side effects. Recent work has revealed substantial genetic variability among equine theileriosis organisms, and analysis of ribosomal DNA from affected animals around the world indicates that the organisms can be grouped into five distinct clades. As these diverse parasites are capable of infecting a wide range of both tick and mammalian hosts, movement of different equine Theileria species between endemic countries, and eventually into non-endemic countries, is a significant concern. Furthermore, the substantial genetic variability of these organisms will likely render currently utilized importation diagnostic tests unable to detect all equine Theileria spp. To this end, more complete characterization of these diverse parasites is critical to the continued global control of equine theileriosis. This review discusses current knowledge of equine Theileria spp. in this context, and highlights new opportunities and challenges for workers in this field.
The role of contrast-enhanced ultrasound (CEUS) in the evaluation of scrotal trauma: a review
Authors: Yusuf Gibran T. , Rafailidis Vasileios , Moore Stephen , Hawthorn Benjamin , Fang Cheng , Huang Dean Y. , Sellars Maria E. , Sidhu Paul S.
Published: May 2020

Testicular trauma is common, usually trivial and rarely requires hospital attendance, but if it does, then imaging becomes essential as scrotal assessment may be difficult due to pain and/or scrotal disruption. Ultrasound (US) assumes a crucial role as other cross-sectional modalities have a limited use in the acute presentation. Despite the acceptable accuracy of conventional US techniques, there are limitations which hinder a thorough evaluation, critically the assessment of tissue viability, crucial for clinical management and prognosis. Contrast-enhanced ultrasound (CEUS) has been shown to offer improved flow visualisation and tissue perfusion compared with conventional Doppler techniques. CEUS can accurately and confidently demonstrate the viability of testicular parenchyma, delineate fracture lines and haematomas and guide treatment for testis-sparing surgery or orchidectomy. The purpose of this review is to present the literature, familiarise physicians with the principles of CEUS and findings of scrotal trauma and illustrate the main abnormalities through characteristic and educative cases.
PD-L1 expression correlation with metabolic parameters of FDG PET/CT and clinicopathological characteristics in non-small cell lung cancer
Authors: Wu Xiaodong , Huang Yan , Zhao Qingping , Wang Lei , Song Xiao , Li Yi , Jiang Lei
Published: May 2020

Background

Immunotherapy targeting programmed cell death 1 (PD-1) or its ligand 1 (PD-L1) has shown promising results in non-small cell lung cancer (NSCLC) patients. Exploring PD-L1 expression could help to select NSCLC candidates for immunotherapy. Fluorine-18 fluorodeoxyglucose (FDG) PET/CT could provide phenotypic information on malignant tumors. Thus, this study investigated PD-L1 expression correlation with metabolic parameters of FDG PET/CT and clinicopathological characteristics in NSCLC.

Methods

FDG PET/CT metabolic parameters including maximum standard uptake (SUVmax), metabolic tumor volume and total lesion glycolysis of primary lesion (MTV-P, TLG-P), and combination of primary lesion and metastases (MTV-C, TLG-C) were compared with PD-L1-positive expression in patients with NSCLC. Moreover, clinicopathological characteristics, including age, gender, smoking history, serum tumor markers, tumor location, size, TNM stage, and genetic mutation were also reviewed.

Results

All 374 patients (215 men; 159 women; age 63 ± 9 years) included 283 adenocarcinomas (ACs) and 91 squamous cell carcinomas (SCCs). PD-L1 expression was positive in 27.8% (104/374) cases. SUVmax, TLG-P, and TLG-C of PD-L1 positivity were significantly higher than PD-L1 negativity. Moreover, PD-L1 expression was obviously correlated with man, smoking, and central NSCLC. If ACs and SCCs were separately analyzed, PD-L1 positivity in ACs and SCCs was 21.6% (61/283) and 47.5% (43/91), respectively, and only SUVmax was obviously associated with PD-L1 expression. Furthermore, multivariate analysis revealed that only SUVmax was an independent predictor of PD-L1 positive expression in overall NSCLC, AC, and SCC. Using a SUVmax cut-off value of 12.5, PD-L1 status of NSCLC was predicted by FDG PET/CT with sensitivity, specificity, and accuracy of 65.4%, 86.7%, and 80.7%, respectively.

Conclusions

PD-L1 expression of NSCLC was related to SUVmax, TLG, man, smoking, and central location. However, only SUVmax was an independent predictor of PD-L1 positivity, which could help to explore the existence of immune checkpoints.
Predicting the occurrence of multidrug-resistant organism colonization or infection in ICU patients: development and validation of a novel multivariate prediction model
Authors: Wang Li , Huang Xiaolong , Zhou Jiating , Wang Yajing , Zhong Weizhang , Yu Qing , Wang Weiping , Ye Zhiqiao , Lin Qiaoyan , Hong Xing , Zeng Ping , Zhang Minwei
Published: May 2020

Background

Multidrug-resistant organisms (MDROs) have emerged as an important cause of poor prognoses of patients in the intensive care unit (ICU). This study aimed to establish an easy-to-use nomogram for predicting the occurrence of MDRO colonization or infection in ICU patients.

Methods

In this study, we developed a nomogram based on predictors in patients admitted to the ICU in the First Affiliated Hospital of Xiamen University from 2016 to 2018 using univariate and multivariate logistic regression analysis. We externally validated this nomogram in patients from another hospital over a similar period, and assessed its performance by calculating the area under the receiver operating characteristic (ROC) curve (AUC) and performing a decision curve analysis.

Results

331 patients in the primary cohort and 181 patients in the validation cohort were included in the statistical analysis. Independent factors derived from the primary cohort to predict MDRO colonization or infection were male sex, higher C-reactive protein (CRP) levels and higher Pitt bacteremia scores (Pitt scores), which were all assembled in the nomogram. The nomogram yielded good discrimination with an AUC of 0.77 (95% CI 0.70–0.84), and the range of threshold probabilities of decision curves was approximately 30–95%.

Conclusion

This easy-to-use nomogram is potentially useful for predicting the occurrence of MDRO colonization or infection in ICU patients.
In vitro evaluation of double carbapenem and colistin combinations against OXA-48, NDM carbapenemase-producing colistin-resistant Klebsiella pneumoniae strains
Authors: Erdem Fatma , Abulaila Ayham , Aktas Zerrin , Oncul Oral
Published: May 2020

Background

Treatment of pandrug-resistant isolates often necessitates combination therapy. Checkerboard synergy and time-killing assay tests were performed to evaluate the benefits of a triple combination with meropenem, ertapenem, and colistin against 10 colistin-resistant K. pneumoniae clinical isolates harboring different β-lactamases. (blaOXA-48, blaNDM).

Materials and methods

In this study, ertapenem and meropenem (ERT/MEM), meropenem and colistin (MEM/COL), ertapenem, meropenem and colistin (ERT/MEM/COL) combinations were tested using checkerboard techniques and time-kill assays of each antibiotic alone and in combination against 10 colistin-resistant clinical K. pneumoniae isolates. An analysis of K. pneumoniae isolate B6 using a scanning electron microscope revealed morphologic changes in the cell surface after treatment with each antibiotic both alone and in combination. The whole genome of K. pneumoniae KPNB1 was sequenced using an Ion Torrent PGM sequencer.

Results

According to the checkboard results, synergistic combinations were observed with ertapenem/meropenem (5/10 isolates), meropenem/colistin (7/10) and ertapenem/meropenem/colistin (9/10); no antagonism was observed for all combinations. For the time-kill assay results; synergism and bactericidal effects were observed with meropenem/colistin (10/10) and with ertapenem/meropenem/colistin (10/10) combinations, and an indifference effect was observed with the ertapenem and meropenem (10/10) combination. Strain number 1 was found 100% identical to Klebsiella pneumoniae subsp. pneumoniae HS11286 according to the outcomes of complete genome sequence analysis, and the strain carried the genes blaOXA-181, blaCTXM-15, blaNDM, arr-3, aac (6′)-Ib-cr, rmtF, and catB1.

Conclusion

Using double carbapenem antibiotics with colistin could be a potential alternative to treat colistin and carbapenem-resistant K. pneumoniae. The present study is the first Turkish report of OXA–181-type carbapenemase causing colistin resistance.
Sentiment analysis of online product reviews using DLMNN and future prediction of online product using IANFIS
Authors: Sasikala P. , Mary Immaculate Sheela L.
Published: May 2020

A major task that the NLP (Natural Language Processing) has to follow is Sentiments analysis (SA) or opinions mining (OM). For finding whether the user’s attitude is positive, neutral or negative, it captures each user’s opinion, belief, and feelings about the corresponding product. Through this, needed changes can well be done on the product for better customer contentment by the companies. Most of the existent techniques on SA aimed at these online products have extremely low accuracy and also encompassed more time amid training. By employing a Deep learning modified neural network (DLMNN), a technique is proposed aimed at SA of online products review; in addition, via Improved Adaptive Neuro-Fuzzy Inferences System (IANFIS), a technique is proposed aimed at future prediction of online products to trounce the above-stated issues. Firstly, the data values are separated into Contents-based (CB), Grades-based (GB), along with Collaborations based (CLB) setting as of the dataset. Then, each setting goes via review analysis (RA) by employing DLMNN, which renders the results as negative, positive, in addition to neutral reviews. IANFIS carry out a weighting factor and classification on the product for upcoming prediction. In the experimental assessment, the proposed work gave an enhanced performance compared to the existing methods.
A potential prognostic model based on miRNA expression profile in The Cancer Genome Atlas for bladder cancer patients
Authors: Liu Yan , Zhu Dong Yan , Xing Hong Jian , Hou Yi , Sun Yan
Published: May 2020

Background

This study aimed to construct prognostic model by screening prognostic miRNA signature of bladder cancer.

Methods

The miRNA expression profile data of bladder cancer (BC) in The Cancer Genome Atlas (TCGA) were obtained and randomly divided into the training set and the validation set. Differentially expressed miRNAs (DEMs) between BC and normal control samples in the training set were firstly identified, and DEMs related to prognosis were screened by Cox Regression analysis. Then, the MiR Score system was constructed using X-Tile based cutoff points and verified in the validation set. The prognostic clinical factors are selected out by univariate and multivariate Cox Regression analysis. Finally, the mRNAs related to prognosis were screened and the biological pathway analysis was carried out.

Results

We identified the 7-miRNA signature was significantly associated with the patient’s Overall Survival (OS). A prognostic model was constructed based on the prognostic 7-miRNA signature, and possessed a relative satisfying predicted ability both in the training set and validation set. In addition, univariate and multivariate Cox Regression analysis showed that age, lymphovascular invasion and MiR Score were considered as independent prognostic factors in BC patients. Furthermore, based on MiR Score prognostic model, several differentially expressed genes (DEGs), such asWISP3andUNC5C, as well as their related biological pathway(s), including cell–cell adhesion and neuroactive ligand-receptor interaction, were considered to be related to BC prognosis.

Conclusion

The prognostic model which was constructed based on the prognostic 7-miRNA signature presented a high predictive ability for BC.
Investigating liquidity constraints as a channel of contagion: a regime switching approach
Authors: Sruthi Rajan , Shijin Santhakumar
Published: May 2020

The present study investigates the timing and repercussion of the subprime crisis of 2008–09 in a regime-switching model. The interdependence and co-movement of financial markets in different countries has been enhanced due to the globalization of international trade, and investment trends can spread globally as a result of investors owning international portfolios. This study uses a regime-switching model to illustrate the timing of the crisis regime and calm regime for United States (US) stock index returns and the corresponding impact on Indian stock index returns. The Indian stocks investigated are classified into “remote” and “reachable” stocks, and different effects are found for these two types. It is found that shocks originating in the US can be transferred to the Indian reachable market as a result of foreign investors. There is, however, a less persistent impact on remote stocks. Accordingly, the study contributes to the literature on the material impacts of the crisis resulting from liquidity constraints and fear of contagion among investors.
Giant congenital melanocytic nevus of the scalp: from clinical-histological to molecular diagnosis
Authors: Sun Yi , Zou Yun , Wang Lizhen , Gu Hao , Cen Qingqing , Chen Hui , Lin Xiaoxi , Cai Ren
Published: May 2020

Congenital melanocytic nevus (CMN) is a benign proliferative skin disease in the epidermis and dermis. Large to giant CMNs are estimated to be associated with an increased lifetime risk of malignancy. It is necessary to estimate and monitor the risk of malignant transformation for giant CMNs. To date, the clinical “ABCD” criteria and immunohistochemistry studies can be confusing and, to some extent, subjective. Accordingly, the elucidation of genomic analyses of nevi is required to better understand the malignant transformation of CMNs. Here, we describe two large to giant CMNs of the scalp with opposite clinical-histological and molecular evaluations of potential malignancy risk. To our knowledge, this is the first description of a genetic study of large to giant CMNs of the scalp in East Asia. We recommend reviewing the molecular diagnosis together with careful medical history and histological information to facilitate the evaluation of the potential malignancy risk.
Evaluation of Toxoplasma gondii infection in western Iran: seroepidemiology and risk factors analysis
Authors: Mousavi-Hasanzadeh Morteza , Sarmadian Hossein , Ghasemikhah Reza , Didehdar Mojtaba , Shahdoust Maryam , Maleki Mahshid , Taheri Mahdieh
Published: May 2020

Background

Toxoplasmosis is a parasitic infectious disease, and Toxoplasma gondii is the causative factor of this intracellular protozoan disease. Due to the lack of information about the rate of T. gondii in general papulation of Markazi Province in Iran, the current study was conducted to determine the prevalence of toxoplasmosis and the related risk factor analysis in the general population of Markazi Province.

Methods

This cross-sectional study was performed within 6 months on individuals who were referred to diagnostic laboratories in Markazi Province. The demographic and background information of the subjects were collected using a questionnaire. Three milliliters of blood samples was collected from the participants under sterile conditions. The sera were separated and evaluated for levels of anti-Toxoplasma IgG antibody using a commercial enzyme-linked immunosorbent assay (ELISA) method. The collected data were analyzed by the SPSS software using descriptive statistics and chi-square test.

Results

Out of 824 people from the general population of Markazi Province who were investigated in this study, 276 (33.5%) had anti-Toxoplasma antibodies in their blood. According to the logistic regression model, gender variables, location, marital status, and having a cat at home do not affect the chances of contracting the parasite. Furthermore, the chance of contracting the parasite in 41- to 50-year-olds is 0.85 times the one in the 20- to 30-year-olds. The prevalence of toxoplasmosis in men and women in Markazi Province was 33% and 34.5%, respectively.

Conclusion

The mean prevalence of T. gondii infection in the age groups of 20-40, and ≥ 40 years was estimated to be 24.7%, and 40.8%, respectively. These rates were significantly lower than the national results (44%, and 55%, respectively). Therefore, regarding to the health authorities, it is necessary to raise the level of awareness of people of the region, especially at-risk groups about the transmittance and prevention methods, and infection risk factors in order to prevent the occurrence of T. gondii infection and reduce the prevalence and incidence of the disease.
Hypertrophic scars and keloids: a review and current treatment modalities
Authors: Tripathi Sanjeev , Soni Kumud , Agrawal Poornima , Gour Vishal , Mondal Rajesh , Soni Vandana
Published: May 2020

Hypertrophic scars (HTS) are raised, red, rigid, inflexible cell-like, and cosmetic problems precipitated due to multiple underlying dermal injuries such as burn, surgery, and trauma during which aberrant wound healing with more pathological deposition of the extracellular matrix than degradation leads to their spawning. Till date, well established and specific treatments for HTS have not been reported; hence, the need of recent developments is thrusted with novel drug delivery vision. This review will try to encompass all the agogs to HTS, definition, pathophysiology, mechanism of hypertrophic scar formation, the role of growth factors in hypertrophic scarring, and their difference with keloids. Further, it will illuminate the available medicaments and recent advances in novel topical drug delivery systems such as ethosomes, transethosomes, liposomes, solid lipid nanoparticles, and microsponges for treatment of HTS.
Morphological description of the digestive canal in Taeniopygia guttata (zebra finch) and Sturnus vulgaris (starling)
Authors: Taha Ameer M. , AL-Duleemy Abdulaziz S.
Published: May 2020

Background

The present study is designed to identify the morphological description of the digestive tract in two species of different birds; these birds were Taeniopygia guttata (zebra finch) which is granivorous and Sturnus vulgaris (Starling) which is omnivorous.

Results

The results showed that the digestive canal of both birds was similar in the essential structure. It begins with the oropharyngeal cavity, which starts with the beak. The beak appeared different in the outer shape, which depends on the feeding. The mouth palate in both birds contains slit localized in the hard palate. This slit represents as beak nostril. The tongue appeared at the bottom of the oropharyngeal cavity. The esophagus appeared as a muscular tube containing the crop, which is divided into two parts the cervical part and the thoracic region, while the stomach was composed of two clear parts in both birds. The first one was a conical shape called proventriculus. The second was a spherical shape called the gizzard, and they are separated by a transitional zone called the isthmus, which was more apparent in the zebra finch, while the small intestine developed mostly in both birds. It is divided into three parts, which were the duodenum, jejunum, and ileum, as well as the large intestine, which appeared as tube shape, which is the rectum. There was a pair of caecum located in the contact area of the ileum and rectum. The digestive canal ends with the cloaca in both birds.

Conclusion

These results indicate that there are differences in the anatomical structure of the gastrointestinal tract organs between the two birds to be compatible with the quality and method of obtaining food.
Thermoelectric composite with enhanced figure of merit via interfacial doping
Authors: Adams Michael J. , Heremans Joseph P.
Published: May 2020

In order to improve the thermoelectric conversion efficiency and figure of merit, ZT, composite materials of organic or inorganic constituents often are considered. The limitation of this approach is set by the effective medium theory, which states that the ZT in a composite material cannot exceed the greatest value of any single constituent, if the constituents do not interact. Here, we describe a method that circumvents this limit, based on the introduction of interfacial doping. An electrically and thermally insulating medium is distributed into a conventional thermoelectric host material but is coated with an aliovalent acceptor that is allowed to diffuse locally into the host matrix, thereby doping it locally. The thermal conductivity decreases when the insulating material is added, but the more electrically conducting region around the insulator prevents an equally large increase in electrical resistivity. Employing this method in p-type (Bi1-xSbx)2Te3 compounds results in a maximum figure of merit zT = 1.3, an over 10% improvement compared to the host material alone. We report synthesis and measurement techniques in addition to thermoelectric transport properties. While we report on one material system, the concept is not specific to that system and may be used to provide functionality in other thermoelectric composites.
Fused deposition modelling (FDM) of composites of graphene nanoplatelets and polymers for high thermal conductivity: a mini-review
Authors: Guerra Valentina , Wan Chaoying , McNally Tony
Published: May 2020

Composites of polymers and the graphene family of 2D materials continue to attract great interest due their potential to dissipate heat, thus extending the in-service life of electronic and other devices. Such composites can be 3D printed using Fused Deposition Modelling into complex bespoke structures having enhanced properties, including thermal conductivity in different directions. While there are controversial opinions on the limitations of FDM for large-scale and high volume production (e.g. long production times, and expensive printers required), FDM is an innovative solution to the manufacture of small objects where effective thermal management is required and it is a valid alternative for the manufacture of (micro)-electronic components. There are few papers published on the FDM of functional composite materials based on graphene(s). In this mini-review, we describe the many technical challenges that remain to successful printing of these composites by FDM, including orientation effects, void formation, printing and feeding rates, nozzle and printing bed temperatures and the role each has in determining the thermal conductivity of any composite product made by FDM. We also compare these initial reports with those on FDM of other and related carbonaceous fillers, such as multi-walled carbon nanotubes and carbon fibre.
Coordination of cyclic di-GMP and 4-hydroxybenzoic acid in regulating antifungal antibiotic biosynthesis in Lysobacter enzymogenes
Authors: Han Sen , Yang Mingming , Fulano Alex M. , Lin Long , Chou Shan-Ho , Qian Guoliang
Published: May 2020

Small molecules are able to regulate numerous cellular processes through binding to various bacterial receptor proteins, but the mechanisms and functions by which these chemicals coordinate and execute remain poorly understood. 4-hydroxybenzoic acid (4-HBA) and cyclic di-GMP (c-di-GMP) are two such molecules with distinct structures that are produced in Lysobacter enzymogenes to synergistically affect the secretion of an antifungal antibiotic, known as heat-stable antifungal factor (HSAF). In our earlier studies, we showed that CdgL, a YajQ-like protein without DNA-binding domain, was able to physically interact with LysR, a transcription factor, to enhance its binding affinity toward the upstream region of the HSAF biosynthesis operon promoter, hence increasing the HSAF biosynthesis. Interestingly, 4-HBA or c-di-GMP can bind to its cognate receptor of LysR or CdgL, respectively, to regulate the HSAF biosynthesis. Further, c-di-GMP acts by binding to CdgL to induce the dissociation of the CdgL-LysR complex, leading to decreased downstream expression. We now showed that CdgL controlled the transcription of lenB2, which encodes an oxygenase to convert chorismate to 4-HBA. Notably, overexpression of cdgL was found to stimulate lenB2 transcription, which likely increased the intracellular 4-HBA content. Also, 4-HBA could bind to LysR to interrupt the LysR-CdgL complex formation and release of CdgL, which caused a lower affinity of LysR toward DNA and hence decreased HSAF operon expression. These findings, along with our earlier report, allow us to propose a coordination mechanism demonstrating how the HSAF biosynthesis is co-regulated by 4-HBA and c-di-GMP through interactions with their cognate receptors. This new mechanism shall shed light on improving the HSAF yield for practical usage.
The gut microbiome and its potential role in paradoxical anaerobism in pupfishes of the Mojave Desert
Authors: Bhute Shrikant S. , Escobedo Brisa , Haider Mina , Mekonen Yididya , Ferrer Dafhney , Hillyard Stanley D. , Friel Ariel D. , van Breukelen Frank , Hedlund Brian P.
Published: May 2020

Background

Pupfishes frequently enter paradoxical anaerobism in response to endogenously produced or exogenously supplied ethanol in a dose-dependent manner. To decipher the role of the gut microbiota in ethanol-associated paradoxical anaerobism, gut microbial communities were depleted using a cocktail of antibiotics and profiled using 16S rRNA gene sequencing.

Results

Compared to the control group (n = 12), microbiota-depleted fish (n = 12) spent more time in paradoxical anaerobism. Our analysis indicated that the bacterial phylaProteobacteria,Fusobacteria,Bacteroidetes,Firmicutes,Actinobacteria,Patescibacteria, andDependentiaedominated the pupfish gut, which is consistent with other fish gut microbiota. Although the gut microbial communities with and without antibiotic treatment were similarly diverse, they were distinct and the greatest contribution to the dissimilarity (27.38%) was the common fish commensalCetobacterium.

Conclusions

This study reports the first characterization of gut microbial communities of pupfish and suggests the microbiome may play a critical role in regulating metabolic strategies that are critical for survival in extremes of temperature and oxygen concentration. We speculate thatCetobacterium, a primary fermenter, also consumes ethanol through secondary fermentation via an alcohol dehydrogenase and therefore regulates the transition from paradoxical anaerobism to aerobic respiration in fish. Given the wide distribution and abundance ofCetobacteriumin warm-water fishes, this process may be of broad importance, and suggests that the microbiome be carefully considered for both conservation and aquaculture.
What should be done to support the mental health of healthcare staff treating COVID-19 patients?
Authors: Tracy Derek K. , Tarn Mark , Eldridge Rod , Cooke Joanne , Calder James D.F. , Greenberg Neil
Published: May 2020

There is an urgent need to provide evidence-based well-being and mental health support for front-line clinical staff managing the COVID-19 pandemic who are at risk of moral injury and mental illness. We describe the evidence base for a tiered model of care, and practical steps on its implementation.