bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Balanced Proinflammatory and Regulatory Cytokine Signature in Young African Children Is Associated With Lower Risk of Clinical Malaria
Authors: Dobaño Carlota , Nhabomba Augusto J , Manaca Maria N , Berthoud Tamara , Aguilar Ruth , Quintó Llorenç , Barbosa Arnoldo , Rodríguez Mauricio H , Jiménez Alfons , Groves Penny L , Santano Rebeca , Bassat Quique , Aponte John J , Guinovart Caterina , Doolan Denise L , Alonso Pedro L 
Published: October 2018

AbstractBackgroundThe effect of timing of exposure to first Plasmodium falciparum infections during early childhood on the induction of innate and adaptive cytokine responses and their contribution to the development of clinical malaria immunity is not well established.MethodsAs part of a double-blind, randomized, placebo-controlled trial in Mozambique using monthly chemoprophylaxis with sulfadoxine-pyrimethamine plus artesunate to selectively control timing of malaria exposure during infancy, peripheral blood mononuclear cells collected from participants at age 2.5, 5.5, 10.5, 15, and 24 months were stimulated ex vivo with parasite schizont and erythrocyte lysates. Cytokine messenger RNA expressed in cell pellets and proteins secreted in supernatants were quantified by reverse-transcription quantitative polymerase chain reaction and multiplex flow cytometry, respectively. Children were followed up for clinical malaria from birth until 4 years of age.ResultsHigher proinflammatory (interleukin [IL] 1, IL-6, tumor necrosis factor) and regulatory (IL-10) cytokine concentrations during the second year of life were associated with reduced incidence of clinical malaria up to 4 years of age, adjusting by chemoprophylaxis and prior malaria exposure. Significantly lower concentrations of antigen-specific T-helper 1 (IL-2, IL-12, interferon-γ) and T-helper 2 (IL-4, IL-5) cytokines by 2 years of age were measured in children undergoing chemoprophylaxis compared to children receiving placebo (P &lt; .03).ConclusionsSelective chemoprophylaxis altering early natural exposure to malaria blood stage antigens during infancy had a significant effect on T-helper lymphocyte cytokine production &gt;1 year later. Importantly, a balanced proinflammatory and anti-inflammatory cytokine signature, probably by innate cells, around age 2 years was associated with protective clinical immunity during childhood.Clinical Trials RegistrationNCT00231452.
Evaluation of SF3B1 Mutation Screening by High-Resolution Melting Analysis and its Clinical Utility for Myelodysplastic Syndrome with Ring Sideroblasts at the Point of Diagnosis
Authors: Mizuta Shumpei , Yamane Noriko , Komai Takao , Koba Yusuke , Ukyo Naoya , Tamekane Akira , Watanabe Mitsumasa 
Published: October 2018

Abstract

Background
SF3B1 (splicing factor 3B subunit-1) somatic mutation is specifically detected in myelodysplastic syndrome (MDS) with ring sideroblasts (MDS-RS). We investigated the sensitivity and utility of SF3B1 mutation analysis as a clinical laboratory test.

Method
Detection limit for SF3B1 mutations by high-resolution melting (HRM) analysis was investigated by plasmid mixture. In 67 MDS patients, we examined the association between SF3B1 mutation and prognostic evaluation using the Revised International Prognostic Scoring System and revalidated MDS classifications based on the revised 4th edition of the WHO classification.

Results
HRM analysis enabled mutation detection in the 12.5% SF3B1 mutant alleles. SF3B1 mutation was detected in 9 cases, mostly in the low-risk group. Cases of MDS with ring sideroblasts unrelated to SF3B1 mutation were detected in the high-risk group. Two cases were reclassified as MDS-RS after detecting SF3B1 mutation.

Conclusions
SF3B1 mutation analysis as an initial screening at diagnosis increases the accuracy of prognostic prediction and disease classification.
Effects of Zinc Combined with Probiotics on Antibiotic-associated Diarrhea Secondary to Childhood Pneumonia
Authors: Xiang Rong , Tang Qing , Chen Xiu-Qi , Li Mu-Yan , Yang Mei-Xiong , Yun Xiang , Huang Li , Shan Qing-Wen 
Published: October 2018

AbstractAimThe aim of this study was to evaluate the impact of zinc combined with probiotics (Bifico) on antibiotic-associated diarrhea (AAD) secondary to pneumonia.MethodsA total of 50 patients with AAD secondary to pneumonia were randomly divided into a probiotics group (Bifico) and a combined group (zinc combined with Bifico) and 25 pneumonia patients without AAD as the control group. Serum levels of zinc, diamine oxidase (DAO) activity, D-lactate and intestinal flora [Bifidobacterium, Escherichia coli and Bifidobacterium/E. coli (B/E) ratio] were detected before and after intervention.ResultsThe results showed that zinc combined with Bifico had significantly higher overall efficiency than Bifico alone for treatment of AAD secondary to pneumonia. Notably, the combined treatment increased the population of Bifidobacterium, while the number of E. coli was reduced, the B/E value was improved and DAO activity and D-lactate levels were markedly reduced.ConclusionPatients with AAD secondary to pneumonia benefit from zinc supplementation of probiotic treatment.
Gambling and Subsequent Road Traffic Injuries: A Longitudinal Cohort Analysis
Authors: Bhatti Junaid A. , Thiruchelvam Deva , Redelmeier Donald A. 
Published: October 2018

Background:
To compare the risks of a road traffic injury (RTI) crash among adults who were involved in high-risk gambling and those who did not gamble.

Methods:
We conducted a linked longitudinal cohort analysis of adult persons in large population survey conducted during 2007 and 2008 in Ontario, Canada. We used responses to Problem Gambling Severity Index to distinguish persons as nongamblers, no-risk, low-risk, or high-risk gamblers. All persons were subsequently monitored for a subsequent RTI crash as a driver, pedestrian, or bicyclist up to March 31, 2014, through health insurance databases. We estimated relative risks as rate ratios (RRs) with 95% confidence intervals (95% CIs).

Results:
In all, 30,652 adults were included, of whom 52% self-identified as gamblers, including 49% as no-risk gamblers, 2% as low-risk gamblers, and 1% as high-risk gamblers. During a median follow-up period of 6.8 years, 708 participants (2%) were involved in 821 RTI crashes. The absolute risks of an RTI were 6.4 per 1000 person-years (95% CI 3.7–10.4) in high-risk gamblers and 3.6 per 1000 person-years (95% CI 3.2–4.0) in nongamblers. The relative risks for RTI crashes were significantly higher in high-risk gamblers than in nongamblers (adjusted RR 1.68, 95% CI 1.03–2.76). The risks for RTI crashes as a driver were augmented in high-risk gamblers than in nongamblers (RR 1.97, 95% CI 1.13–3.43).

Conclusions:
We found an increased risk of an RTI crash among drivers who self-identified as high-risk gamblers. Further research exploring the underlying mechanisms of these associations might interest health professionals to monitor RTI risks in adults involved in high-risk gambling.
Clinical Presentation and Cranial MRI Findings of Listeria monocytogenes Encephalitis
Authors: Arslan Ferhat , Ertan Gülhan , Emecen Ahmet N. , Fillatre Pierre , Mert Ali , Vahaboglu Haluk 
Published: October 2018

Background:

Listeria monocytogenes–associated encephalitis is a severe clinical condition that can also be seen in immunocompetent patients. Clinical manifestation and radiologic features of this entity need to be elaborated.

Review Summary:
We searched the medical literature during the period spanning from 1991 to 2017 using the keyword “listeria AND (abscess OR brainstem OR encephalit* OR magnetic* OR imaging*).” We included in the review well-documented adult cases with a definitive diagnosis and having magnetic resonance imaging data. Confusion, hemiparesis, cerebellar ataxia, facial paralysis, and gait disturbance were the most frequent findings, detected in >30% of patients during admission. The high rate of facial paralysis was of particular interest. T2 hyperintensity (80/82), contrast enhancement (60/82), and ring-enhancing lesions, which are considered as brain abscess, were found in 46/82 patients. The mortality and neurological sequel rates were 20% and 68%, respectively.

Conclusions:
Listeria encephalitis is a severe disease and should be remembered in cases admitted with symptoms related to the brainstem and cranial nerve dysfunction. Cranial magnetic resonance imaging with brainstem and cerebellum involvements and contrast enhancement with or without abscess are particularly suggestive of the listeria-related infection.
Endoscopic Approach to Remove a Dental Implant With Simultaneous Laser-Cystectomy
Authors: Engelke Wilfried , Beltrán Víctor 
Published: October 2018

Background:
Removal of dental implants from the maxillary sinus may require surgical treatment of comorbidities.

Method:
Canine fossa endoscopy with an additional laterobasal access originally has been used for flapless sinus floor augmentation. The combined technique is presented to remove a titanium screw from the maxillary sinus. The same portals served for dissection of a mucocele using a diode laser.

Conclusions:
The combination of canine fossa endoscopy and laterobasal access allows an appropriate instrumentation and triangulation of the scope for the endoscopically assisted implant removal and dissection of the mucocele.
Utilizing Transcranial Direct Current Stimulation to Enhance Laparoscopic Technical Skills Training: A Randomized Controlled Trial
Authors: Cox Morgan L. , Deng Zhi-De , Palmer Hannah , Watts Amanda , Beynel Lysianne , Young Jonathan R. , Lisanby Sarah H. , Migaly John , Appelbaum Lawrence G. 
Published: October 2018

AbstractThis study aimed to test the efficacy of transcranial direct current stimulation (tDCS) during laparoscopic skill training to determine if it has the capacity to accelerate technical skill acquisition. tDCS is a non-invasive brain stimulation technique that delivers constant, low electrical current resulting in changes to cortical excitability and prior work suggests it may enhance motor learning. We evaluate for the first time the potential of tDCS, coupled with motor skill training, to accelerate the development of laparoscopic technical skills. In this pre-registered, double-blinded and sham-controlled study, 60 healthy subjects were randomized into sham or active tDCS in either bilateral primary motor cortex (bM1) or supplementary motor area (SMA) electrode configurations. All subjects practiced the Fundamental of Laparoscopic Surgery Peg Transfer Task during a pre-test, six 20-minute training sessions, and a post-test. The primary outcome was change in laparoscopic skill performance over time, quantified by improvement in performance according to a seconds-per-object calculated score accounting for errors. Sixty participants were randomized equally into the three training cohorts (active bM1, active SMA, sham). The active groups had significantly greater improvement in performance from pre-test to post-test compared to the sham groups (108 vs 76 seconds, p = 0.018). Both bM1 and SMA active cohorts had significantly greater improvement in learning (p < 0.01), achieving the same skill level in 4 sessions compared to the 6 sessions required of the sham cohort. The SMA cohort had more variability in performance compared to the bM1 and control cohorts. Laparoscopic skill training with active, bM1 or SMA, tDCS exhibited significantly greater learning relative to training with sham tDCS. The potential for tDCS to enhance the training of surgical skills merits further investigation to determine if these preliminary results may be replicated.
Generation and characterization of iPSCs from human embryonic dermal fibroblasts of a healthy donor from Siberian population
Authors: Grigor’eva Elena V. , Malankhanova Tuyana B. , Surumbayeva Aizhan , Minina Julia M. , Kizilova Elena A. , Lebedev Igor N. , Malakhova Anastasia A. , Zakian Suren M. 
Published: October 2018

AbstractTechnology of reprogramming of somatic cells to a pluripotent state allows generating induced pluripotent stem cells (iPSCs) and carrying out a broad range of studies. iPSCs can be obtained from patients suffering from inherited diseases to model the diseases and to study their pathological mechanisms at the molecular level after iPSC differentiation in relevant cell types. Another approach to model and study inherited diseases is using iPSCs from healthy donors and genome editing tools. The approach allows generating a panel of isogenic lines, which gives new opportunities in drug screening and toxicological testing. Moreover, iPSCs and their derivatives can be further used for substitutive cell therapy and transplantology.In this study, we generated iPSCs from human embryonic fibroblasts using episomal vectors. The lines obtained expressed pluripotency markers, had a stable karyotype – 46:XY, and did not contain episome integrations into genome. The cell lines gave rise to derivatives of three germ layers during spontaneous differentiation in vitro and in vivo.
CSTDB: A Crop Stress-tolerance Gene and Protein Database Integrated by Convolutional Neural Networks
Authors: Zhang Di , Yue Yi , Zhao Yang , Wang Chao , Cheng Xi , Wu Ying , Fan Guohua , Wu Panrong , Gao Yujia , Zhang Youhua , Wu Yunzhi 
Published: October 2018

AbstractNumerous studies have shown that many genes and proteins in plants are involved in the regulation of plant resistance to abiotic and biotic stresses. The researches on the stress tolerance of crops are also the focus of many researchers. To provides a reliable platform for collecting and retrieving genetic and protein information related to stress tolerance found in crops, we constructed CSTDB(Crops Stress-tolerance Database), an integrated database that includes stress-tolerance genes and proteins for many crop species. The database was developed based on convolutional neural network technology. It is a web-accessible database that contains detailed information on the stress-tolerance genes and proteins of major crop species. Currently, the database records four major crops containing 1,371 abiotic stress-tolerance genes or proteins, and 207 genes or proteins associated with biotic stress. Each gene and protein has detailed functional information and sequence information, such as stress types, Genbank ID, Pubmed ID, Protein ID, 3D model picture and FASTA files. As a user-friendly browsing tool, this database provides search functions, BALST functions and file download functions. CSTDB can be a valuable resource, which is designed to meet the broad needs of researchers working on crops stress-tolerance experiments. Database URL:http://pcsb.ahau.edu.cn:8080/CSTDB
A transgenic zebrafish line for in vivo visualisation of neutrophil myeloperoxidase
Authors: Buchan Kyle D. , Prajsnar Tomasz K. , Ogryzko Nikolay V. , de Jong Nienke W.M. , van Gent Michiel , Kolata Julia , Foster Simon J. , van Strijp Jos A.G. , Renshaw Stephen A. 
Published: October 2018

AbstractThe neutrophil enzyme myeloperoxidase (MPO) is a major enzyme made by neutrophils to generate antimicrobial and immunomodulatory compounds, notably hypochlorous acid (HOCl), amplifying their capacity for destroying pathogens and regulating inflammation. Despite its roles in innate immunity, the importance of MPO in preventing infection is unclear, as individuals with MPO deficiency are asymptomatic with the exception of an increased risk of candidiasis. Dysregulation of MPO activity is also linked with inflammatory conditions such as atherosclerosis, emphasising a need to understand the roles of the enzyme in greater detail. Consequently, new tools for investigating granular dynamicsin vivocan provide useful insights into how MPO localises within neutrophils, aiding understanding of its role in preventing and exacerbating disease. The zebrafish is a powerful model for investigating the immune systemin vivo, as it is genetically tractable, and optically transparent.To visualise MPO activity within zebrafish neutrophils, we created a genetic construct that expresses human MPO as a fusion protein with a C-terminal fluorescent tag, driven by the neutrophil-specific promoterlyz. After introducing the construct into the zebrafish genome by Tol2 transgenesis, we established theTg(lyz:Hsa.MPO-mEmerald,cmlc2:EGFP)sh496line, and confirmed transgene expression in zebrafish neutrophils. We observed localisation of MPO-mEmerald within a subcellular location resembling neutrophil granules, mirroring MPO in human neutrophils. In Spotless (mpxNL144) larvae - which express a non-functional zebrafish myeloperoxidase - the MPO-mEmerald transgene does not disrupt neutrophil migration to sites of infection or inflammation, suggesting that it is a suitable line for the study of neutrophil granule function.We present a new transgenic line that can be used to investigate neutrophil granule dynamicsin vivowithout disrupting neutrophil behaviour, with potential applications in studying processing and maturation of MPO during development.
An infant mouse model of influenza virus transmission demonstrates the role of virus-specific shedding, humoral immunity, and sialidase expression by colonizingStreptococcus pneumoniae
Authors: Ortigoza Mila Brum , Blaser Simone , Zafar M. Ammar , Hammond Alexandria , Weiser Jeffrey N. 
Published: October 2018

ABSTRACTThe pandemic potential of influenza A viruses (IAV) depends on the infectivity of the host, transmissibility of the virus, and susceptibility of the recipient. While virus traits supporting IAV transmission have been studied in detail using ferret and guinea pig models, there is limited understanding of host traits determining transmissibility and susceptibility because current animal models of transmission are not sufficiently tractable. Although mice remain the primary model to study IAV immunity and pathogenesis, the efficiency of IAV transmission in adult mice has been inconsistent. Here we describe an infant mouse model which support efficient transmission of IAV. We demonstrate that transmission in this model requires young age, close contact, shedding of virus particles from the upper respiratory tract (URT) of infected pups, the use of a transmissible virus strain, and a susceptible recipient. We characterize shedding as a marker of infectiousness that predicts the efficiency of transmission among different influenza virus strains. We also demonstrate that transmissibility and susceptibility to IAV can be inhibited by humoral immunity via maternal-infant transfer of IAV-specific immunoglobulins, and modifications to the URT milieu, via sialidase activity of colonizingStreptococcus pneumoniae(Spn). Due to its simplicity and efficiency, this model can be used to dissect the host’s contribution to IAV transmission and explore new methods to limit contagion.IMPORTANCEThis study provides insight into the role of the virus strain, age, immunity, and URT flora on IAV shedding and transmission efficiency. Using the infant mouse model, we found that: (a) differences in viral shedding of various IAV strains is dependent on specific hemagglutinin (HA) and/or neuraminidase (NA) proteins; (b) host age plays a key role in the efficiency of IAV transmission; (c) levels of IAV-specific immunoglobulins are necessary to limit infectiousness, transmission, and susceptibility to IAV; and (d) expression of sialidases by colonizing Spn antagonize transmission by limiting the acquisition of IAV in recipient hosts. Our findings highlight the need for strategies that limit IAV shedding, and the importance of understanding the function of the URT bacterial composition in IAV transmission. This work reinforces the significance of a tractable animal model to study both viral and host traits affecting IAV contagion, and its potential for optimizing vaccines and therapeutics that target disease spread.
Loss of flavin adenine dinucleotide (FAD) impairs sperm function and male reproductive advantage inC. elegans
Authors: Yen Chia-An , Ruter Dana L. , Turner Christian D. , Pang Shanshan , Curran Sean P. 
Published: October 2018

ABSTRACTExposure to environmental stress is clinically established to influence male reproductive health, but the impact of normal cellular metabolism on sperm quality is less well-defined. Here we show that impaired mitochondrial proline catabolism, reduces energy-storing flavin adenine dinucleotide (FAD) levels, alters mitochondrial dynamics toward fusion, and leads to age-related loss of sperm quality (size and activity), which reduces competitive fitness. Loss of the 1-pyrroline-5-carboxylate dehydrogenase enzymealh-6that catalyzes the second step in mitochondrial proline catabolism, leads to premature male reproductive senescence. Reducing the expression of the proline catabolism enzymealh-6or FAD biosynthesis pathway genes in the germline is sufficient to recapitulate the sperm-related phenotypes observed inalh-6loss-of-function mutants. These sperm-specific defects are suppressed by feeding diets that restore FAD levels. Our results define a cell autonomous role for mitochondrial proline catabolism and FAD homeostasis on sperm function and specify strategies to pharmacologically reverse these defects.
Gaussian curvature and the budding kinetics of enveloped viruses
Authors: Dharmavaram Sanjay , She Baochen , Lázaro Guillermo , Hagan Michael F. , Bruinsma Robijn 
Published: October 2018

AbstractThe formation of a membrane-enveloped virus such as HIV-1 starts with the assembly of a curved layer of capsid proteins lining the interior of the plasma membrane (PM) of the host cell. This layer grows into a spherical shell enveloped by a lipid membrane that is connected to the PM via a curved neck (“budding”). For many enveloped viruses the scission of this neck is not spontaneous. Instead, the elaborate “ESCRT” cell machinery needs to be recruited to carry out that task. It is not clear why this is necessary since scission is spontaneous for much simpler systems, such as vesiculation driven by phase-separation inside lipid bilayers. Recently, Brownian dynamics simulations of enveloped virus budding reproduced protracted pausing and stalling after formation of the neck [1], which suggest that the origin of pausing/stalling is to be found in the physics of the budding process. Here, we show that the pausing/stalling observed in the simulations can be understood as a purely kinetic phenomenon associated with a “geometrical” energy barrier that must be overcome by capsid proteins diffusing along the membrane prior to incorporation into the viral capsid. This geometrical energy barrier is generated by the conflict between the positive Gauss curvature of the capsid and the large negative Gauss curvature of the neck region. The theory is compared with the Brownian simulations of the budding of enveloped viruses.Author summaryDespite intense study, the life-cycle of the HIV-1 virus continues to pose mysteries. One of these concerns the assembly of the HIV-1 virus inside infected host cells: it is interrupted at the very last moment. During the subsequent pause, HIV-1 recruits a complex cell machinery, the so-called “ESCRT pathway”. The ESCRT proteins pinch-off the “viral bud” from the host cell. In this paper, we propose that the reason for the stalling emerges from the fundamental physics of the lipid membrane that surrounds the virus. The membrane mostly follows the spherical geometry of the virus, but in the pinch-off region the geometry is radically different: it resembles a neck. By combining numerical and analytical methods, we demonstrate that a neck geometry creates a barrier to protein entry, thus blocking proteins required to complete viral assembly. This “geometrical barrier” mechanism is general: such a barrier should form during assembly of all membrane-enveloped viruses – including the Ebola and Herpes viruses. Indeed many families of enveloped viruses also recruit the ESCRT machinery for pinch-off. A fundamental understanding of the budding process could enable a new strategy to combat enveloped viruses, based on selective stabilization of membrane neck geometries.