bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent epidemiology of patients with Gastro-Entero-Pancreatic Neuroendocrine Neoplasms (GEP-NEN) in Japan: a population-based study
Authors: Masui Toshihiko , Ito Tetsuhide , Komoto Izumi , Uemoto Shinji
Published: September 2020

Background: The worldwide prevalence and incidence of neuroendocrine neoplasms (NEN) have been increasing recently, although few studies have analyzed data on the current situation of NENs in Japan. Here, the Japan Neuroendocrine Tumor Society (JNETS) planned to investigate the recent incidence and distribution of these tumors using data from the national cancer registry started in 2016. This study examined the incidence and distribution of primary sites as well as rate of advanced disease from this population-based registry. Methods: A retrospective, population-based study using data from the national cancer registry in Japan (NCR) was conducted to evaluate patients with gastro-entero-pancreatic NEN (GEP-NEN) in 2016. Associated population data were used to determine annual age-adjusted incidences. Results: A total of 6735 individuals were diagnosed with GEP-NEN in Japan in 2016. Annual onset incidence was 0.70/100,000 for pancreatic NEN and 2.84/100,000 for gastrointestinal NEN. NEN in the ileum accounted for only 1% of total GEP-NENs in Japan. Most NENs in the esophagus or lungs were neuroendocrine carcinomas (NECs), while the majority of those in the duodenum, ileum, appendix and rectum were grade 1 neuroendocrine tumors (NETs). Median age at initial diagnosis was in between 60 to 65. Tumors in the duodenum, appendix and rectum were mostly limited to local, while those in the esophagus, stomach and colon tended to show distant metastasis. In Japan, initial treatment for GEP-NENs was resection even if the tumor was NEC.Conclusions: This is the first report of a national registry-based incidence and distribution of GEP-NEN in Japan. These data will serve as an important first step to determining the exact etiology and trends for this pathology in Japan.
Serum lithium test requesting across three UK regions: An evaluation of adherence to monitoring guidelines
Authors: Parfitt Ceri , Duff Christopher J , Scargill Jonathan , Green Lewis , Holland David , Heald Adrian H , Fryer Anthony
Published: September 2020

Background: Bipolar disorder is the fourth most common mental health condition, affecting ~1% of UK adults. Lithium is an effective treatment for prevention of relapse and hospital admission, and is widely recommended as a first-line treatment. We previously showed in other areas that laboratory testing patterns are variable with sub-optimal conformity to guidance. We therefore examined lithium results and requesting patterns relative to monitoring recommendations.Methods: Data on serum lithium levels and intervals between requests were extracted from Clinical Biochemistry laboratory information systems at the University Hospitals of North Midlands, Salford Royal Foundation Trust and Pennine Acute Hospitals from 2012-2018 (46,555 requests; 3,371 individuals). Data were examined with respect to region/source of request, age and sex.Results: Across all sites, lithium levels on many requests were outside the recommended UK therapeutic range (0.4-0.99 mmol/L); 19.2% below the range and 6.1% above the range (median [Li]: 0.60 mmol/L). A small percentage were found at the extremes (3.2% at <0.1mmol/L, 1.0% at ≥1.4mmol/L). Most requests were from general practice (56.3%) or mental health units (34.4%), though those in the toxic range (≥1.4 mmol/L) were more likely to be from secondary care (63.9%). For requesting intervals, there was a distinct peak at 12 weeks, consistent with guidance for those stabilised on lithium therapy. There was no peak at 6 months, as recommended for those aged <65 years on unchanging therapy, though re-test intervals in this age group were more likely to be longer. There was a peak at 0-7 days, reflecting those requiring closer monitoring (e.g. treatment initiation, toxicity). However, for those with initial lithium concentrations within the BNF range (0.4-0.99 mmol/L), 69.4% of tests were requested outside expected testing frequencies.Conclusions: Our data showed: (a) lithium levels are often maintained at the lower end of the recommended therapeutic range, (b) patterns of lithium results and testing frequency were comparable across three UK sites with differing models of care and, (c) re-test intervals demonstrate a noticeable peak at the recommended 3-monthly, but not at 6-monthly intervals. Many tests were repeated outside expected frequencies, indicating the need for measures to minimise inappropriate testing.
SlGT11 Controls Floral Organ P atterning and F loral Determinacy in Tomato
Authors: Yang Liling , Qi Shilian , touqeer Arfa , Li Haiyang , Zhang Xiaolan , Liu XiaoFeng , wu shuang
Published: September 2020

Background: Flower development directly affects fruit production in tomato. Despite the framework mediated by ABC genes have been established in Arabidopsis, the spatiotemporal precision of floral development in tomato has not been well examined.Results: Here, we analyzed a novel tomato stamenless like flower (slf) mutant in which the development of stamens and carpels is disturbed, with carpelloid structure formed in the third whorl and ectopic formation of floral and shoot apical meristem in the fourth whorl. Using bulked segregant analysis (BSA), we assigned the causal mutation to the gene Solanum lycopersicum GT11 (SlGT11) that encodes a transcription factor belonging to Trihelix gene family. SlGT11 is expressed in the early stages of the flower and the expression becomes more specific to the primordium position corresponding to stamens and carpels in later stages of the floral development. Further RNAi silencing of SlGT11 verifies the defective phenotypes of the slf mutant. The carpelloid stamen in slf mutant indicates that SlGT11 functions like as a B-type gene in the third whorl. The failed termination of floral meristem and the occurrence of floral reversion in slf indicate that SlGT11 also functions as a C-type gene in the fourth whorl. Furthermore, we find that at higher temperature, the defects of slf mutant are substantially enhanced, with petals transformed into sepals, all stamens disappeared, and the frequency of ectopic shoot/floral meristem in fourth whorl increased, indicating that SlGT11 may have the function of tomato B and E class gene in the development of second and fourth whorls.Conclusions: Together with the spatiotemporal expression pattern, we suggest that SlGT11 functions in floral organ patterning and maintenance of floral determinacy in tomato.
Long-term safety and effectiveness of etanercept in JIA: an 18-year experience from the BIKER registry
Authors: Armaroli Giulia , Klein Ariane , Ganser Gerd , Ruehlmann Michael J. , Dressler Frank , Hospach Anton , Minden Kirsten , Trauzeddel Ralf , Foeldvari Ivan , Kuemmerle-Deschner Jasmin , Weller-Heinemann Frank , Urban Andreas , Horneff Gerd
Published: September 2020

Background: At present, etanercept represents the most commonly prescribed biologic agent for juvenile idiopathic arthritis (JIA) treatment. Children and adolescents with JIA are often treated with etanercept over long periods, sometimes even into adulthood. The objectives of this analysis were to determine the long-term safety of etanercept compared to a biologic-naïve cohort, and to assess the long-term treatment response upon continuous etanercept exposure using data from the German biologics registry (BiKeR).

Methods: JIA patients newly exposed to etanercept were documented in the BiKeR registry from January 2001 till March 2019, and baseline characteristics, effectiveness, as well as safety parameters were analysed. Response to treatment was assessed according to 10-joint Juvenile Arthritis Disease Activity Score (JADAS10), JADAS-defined minimal disease activity and remission, JIA-American College of Rheumatology (ACR) improvement criteria, as well as ACR-inactive disease definition. Safety assessments were based on adverse events (AE) reports.

Results: 2725 new etanercept users with a diagnosis of JIA were registered. Of these, etanercept was received as a first-line biologic by 95.8% and as monotherapy without concomitant methotrexate by 31.5%. After nine years on continuous treatment, 68.1% of patients presented minimal disease activity, 43.1% JADAS-defined remission on drug and 36.6% ACR-inactive disease. JIA-ACR30/50/70/90 response rates were still 82/79/71/54% after 9 years of treatment. Overall, 2053 AEs (34.3/100PY), including 226 serious AEs (SAE, 3.8/100PY), were observed upon etanercept, compared to 1345 AEs [35.6/100PY; p=0.3] and 52 SAEs (1.4/100PY; p=0.0001) in the biologic-naïve cohort. Respective exposure-adjusted rates for etanercept and biologic-naïve patients were 0.9/100PY and 0.2/100PY (p=0.0001) for serious infections, 0.4/100PY and 0.1/100PY (p=0.01) for zoster reactivation, 0.3/100PY and 0.03/100PY (p=0.015) for inflammatory bowel disease, 1.9/100PY and 1.4/100PY (p=0.09) for uveitis. Three and two malignancies were documented in the etanercept and biologic-naïve groups, as well as three and one deaths, respectively.

Conclusions: No new safety signal was observed, especially no increased risk for malignancies or autoimmune disorders other than inflammatory bowel disease. However, SAEs and serious infections, though infrequent, were more often reported on etanercept than in biologic-naïve patients. In addition, etanercept demonstrated a long-term maintenance of clinical benefits up to nine years of continuous treatment.
Keywords: Juvenile idiopathic arthritis, JIA-treatment, etanercept, TNF-inhibitors, biologics registry, drug surveillance
Symbiotic microbiome Staphylococcus aureus from human nasal mucus modulates IL-33-mediated type 2 immune responses in allergic nasal mucosa
Authors: Jeon Yung Jin , Gil Chan Hee , Won Jina , Jo Ara , Kim Hyun Jik
Published: September 2020

Background: The host-microbial commensalism can shape the innate immune responses in respiratory mucosa and nasal microbiome also modulates front-line immune mechanism in the nasal mucosa. Inhaled allergens encounter the host immune system first in the nasal mucosa, and microbial characteristics of nasal mucus directly impact the mechanisms of initial allergic responses in nasal epithelium. However, the roles of the nasal microbiome in allergic nasal mucosa remain uncertain. We sought to determine the distribution of nasal microbiomes in allergic nasal mucosa and elucidate the interplay between nasal microbiome Staphylococcus species and Th2 cytokines in allergic rhinitis (AR) models.Results: Staphylococcus aureus (AR-SA) and S. epidermidis (AR-SE) were isolated from the nasal mucosa of patients with AR. The influence of nasal microbiome Staphylococcus species on allergic nasal mucosa was also tested with in vitro and in vivo AR models. Pyrosequencing data showed that colonization by S. epidermidis and S. aureus was more dominant in nasal mucus of AR subjects. The mRNA and protein levels of IL-33 and TSLP were significantly higher in AR nasal epithelial (ARNE) cells which were cultured from nasal mucosa of AR subjects, and exposure of ARNE cells to AR-SA reduced IL-33 mRNA and secreted protein levels. Particularly, ovalbumin-driven AR mice inoculated with AR-SA by intranasal delivery exhibited significantly reduced IL-33 in their nasal mucosa. In the context of these results, allergic symptoms and Th2 cytokine levels were significantly downregulated after intranasal inoculation of AR-SA in vivo AR mice. Conclusion: Colonization by Staphylococcus species was more dominant in allergic nasal mucosa, and nasal commensal S. aureus from subjects with AR mediates anti-allergic effects by modulating IL-33-dependent Th2 inflammation. The results demonstrate the role of host-bacterial commensalism in shaping human allergic inflammation.
Efficacy of Orbital Radiotherapy in Moderate-to-Severe Active Graves’ Orbitopathy Including Long-lasting Disease
Authors: Choi Jin Hwa , Lee Jeong Kyu
Published: September 2020

Background: We aimed to explore the efficacy of orbital radiotherapy (RT) in patients with moderate-to-severe active Graves’ orbitopathy (GO), including long-lasting disease, and to determine the predictive factors associated with treatment response.Methods: This was a retrospective study of 62 moderate-to-severe active GO patients treated with RT. Demographic data and ophthalmic findings prior to RT and at 3 and 6 months afterward were analyzed. Computed tomography was performed before and after RT to compare orbital volume change. We used logistic regression to determine the predictive factors for treatment response. Subjects were divided into early- and late-active phase groups based on GO duration of 24 months and treatment outcomes were compared with each other to observe the effects of RT timing on treatment response.Results: Forty (64.5%) and forty-six (74.1%) patients experienced improvements in GO at 3 and 6 months after radiotherapy, respectively. Ocular parameters such as clinical activity score (CAS), proptosis, extraocular muscle (EOM) limitation, and compressive optic neuropathy (CON) were improved by RT. Volumes of EOM significantly decreased after RT. The enlargement of EOMs and EOM limitation were predictive factors for a good response to RT. At 6 months after RT, 22 (68.8%) patients of late-active phase group exhibited improvement in GO, which is comparable to the number of 24 (80.0%) patients of early-active phase group. In the late-active phase group, CAS, diplopia, and visual acuity were improved significantly, but there was no change in EOM limitation.Conclusions: In moderate-to-severe active GO patients, orbital RT may help improve high CAS, proptosis, EOM limitation, and CON. The orbital RT in long-lasting active GO patients may be considered as treatments for the relief of symptoms including high CAS and poor visual acuity.
Circulating Cytokine Profiles of Polyparasitized Individuals in Gabon.
Authors: M'Bondoukwé Noé Patrick , Moutongo Reinne , Gbédandé Komi , Ngomo Jacques Mari Ndong , Hountohotegbe Tatiana , Adamou Rafiou , Lengongo Jeanne Vanessa Koumba , Bello Kowir Pambo , Mawili-Mboumba Denise Patricia , Luty Adrian John Frederick , Bouyou-Akotet Marielle Karine
Published: September 2020

Background: Malaria, blood-borne filarial worms and intestinal parasites are all endemic in Gabon. This geographical co-distribution leads to polyparasitism and consequently, the possibility of immune-mediated interactions between different parasite species. Intestinal protozoa and helminths could modulate anti-malarial immunity, for example, thereby potentially increasing or reducing susceptibility to malaria. Methods: Blood and stool samples were collected during cross-sectional surveys in five provinces of Gabon. Parasitological diagnosis was performed to detect plasmodial parasites, Loa loa, Mansonella perstans, intestinal helminths (STH) and protozoan parasites. Nested PCR was used to detect submicroscopic plasmodial infection in individuals with negative blood smears. Cytometric Bead Array was used to quatify interleukin (IL)-6, IL-10 and Tumor Necrosis Factor (TNF)-α in plasma of subjects with different parasitological profiles. Results: Median IL-6 and IL-10 levels and the median IL-10/TNF- α ration were all significantly higher among individuals with Plasmodium (P.) falciparum infection compared to other groups ( P ≤0.0001). The median TNF-α level and IL-10/IL-6 ratio were higher in subjects with STH ( P =0.09) and P. falciparum -intestinal protozoa co-infection ( P =0.04), respectively. IL-6 (r=-0.37; P ≤0.01) and IL-10 (r=-0.37; P ≤0.01) levels, and the IL-10/TNF-α ratio (r=-0.37; P ≤0.01) correlated negatively with age. Among children under five years old, the IL-10/TNF-α and IL-10/IL-6 ratios were higher in those with intestinal protozoan infections compared to uninfected children. The IL-10/TNF-α ratio was also higher in children aged 5-15 years and in adults harbouring blood-borne filariae compared to their control counterparts, whereas the IL-10/IL-6 ratio was lower in those aged 5-15 years with filariae and intestinal parasites but higher in adults with intestinal parasitic infections. Conclusion: Asymptomatic malaria is associated with a strong polarization towards a regulatory immune response, presenting high circulating levels of IL-10. P. falciparum/intestinal protozoa co-infections are associated with an enhanced IL-10 response. Immunity against malaria could differ according to age and carriage of other parasites.
Dental Students’ Notetaking: a Thematic, Material-based Interview Study
Authors: Lindberg Viveca , Jounger Sofia Louca , Christidis Maria , Christidis Nikolaos
Published: September 2020

Background: The transition from upper secondary to higher education and from higher education to professional practice requires that students need to adapt to new literacy practices, academic and professional. The aim of this study was to identify what characterizes dental students’ notetaking and secondarily to determine what dental students express regarding their notetaking.Methods: Three undergraduate dental students participated in this material-based, semi-structured interview study, that was framed within a New Literacy Studies approach. To analyze the outcome of the interviews a thematic analysis was used. Results: Eight themes that relate to what, how and for what purpose students write were discerned. These include a) what: T1-Professional vocabulary; T2-Core content; T3-Clinical example; b) how: T4-Multimodal accentuation; T5-Synthesis; and c) for what purpose: T6-Mnemonic strategies; T7-Academic purposes; and T8 professional purposes.Conclusions: Findings from the interviews indicate that the digital development, offering a variety of available tools, has expanded the notion of notetaking. Thus, this study identified that dental students’ notetaking has changed during their education from initially just being synchronous, to now also include both multimodal and asynchronous writing, making the notetaking more of a writing practice. Further, students’ writing practices seem to be motivated by their knowledge formation in relation to a subject matter, but also in relation to their experiences during clinical training. Although our hypothesis was that the main purpose of notetaking and writing was to pass their course examinations, this study showed that students, half-way through their dental education, are aware that literacy practices are not only for passing their exams, but also for learning for their future profession.
Clinical characteristics and manifestations in older patients with COVID-19
Authors: Wei Chenchen , Liu Ya , Liu Yapeng , Zhang Kai , Su Dezhen , Zhong Ming , Meng Xiao
Published: September 2020

Background: To investigate the clinical characteristics and manifestations of older patients with coronavirus disease 2019 (COVID-19).Methods: In this retrospective study, 566 patients with confirmed COVID-19 were enrolled and the clinical characteristics, laboratory findings, complications and outcome data were collected and analyzed.Results: Among the 566 patients (median age, 61.5 years) with COVID-19, 267 (47.2%) patients were male and 307 (54.2%) were elderly. Compared with younger patients, older patients had more underlying comorbidities and laboratory abnormalities. A higher rate of acute respiratory distress syndrome (ARDS), acute cardiac injury and heart failure was observed in the older group as compared with younger and middle-aged groups, particularly those oldest-old patients (>75 years) had more multi-organ damage. Older patients with COVID-19 were more likely to suffer from acute cardiac injury in cases with preexistenting cardiovascular diseases, while there was no difference among the three groups when patients had no history of cardiovascular diseases. Older patients present more severe with the mortality of 18.6%, which was higher than that in younger and middle-aged patients (P<0.05). Multivariable analysis showed that age, lymphopenia, ARDS, acute cardiac injury, heart failure and skeletal muscle injury were associated with death in older patients, while glucocorticoids may be harmful.Conclusions: Older patients, especially the oldest-old patients were more likely to exhibit significant systemic inflammation, pulmonary and extrapulmonary organ damage and a higher mortality. Advanced age, lymphopenia, ARDS, acute cardiac injury, heart failure and skeletal muscle injury were independent predictors of death in older patients with COVID19 and glucocorticoids should be carefully administered in older patients.
Clinical educator self-efficacy, self-evaluation and its relationship with student evaluations of clinical teaching
Authors: Vaughan Brett
Published: September 2020

Background

In a whole-of-system approach to evaluation of teaching across any degree, multiple sources of information can help develop an educators’ understanding of their teaching quality. In the health professions, student evaluations of clinical teaching are commonplace however, self-evaluation of teaching is less common, and exploration of clinical educators’ self-efficacy even less so. The aim of the study was to evaluate how a clinical educator’s self-evaluation of teaching intersects with their self-efficacy, to ascertain if that matches student evaluation of their teaching. This information may assist in facilitating targeted professional development to improve teaching quality.

Methods

Clinical educators in the osteopathy program at Victoria University (VU) were invited to complete: a) self-evaluation version of the Osteopathy Clinical Teaching Questionnaire (OCTQ); and b) the Self-Efficacy in Clinical Teaching (SECT) questionnaire. Students in the VU program completed the OCTQ for each of the clinical educators they worked with during semester 2, 2017.

Results

Completed OCTQ and SECT were received from 37 clinical educators. These were matched with 308 student evaluations (mean of 6 student ratings per educator). Three possible educator cohorts were identified: a) high clinical eductor self-OCTQ with low student evaluation; b) low clinical educator self-evaluation and high student evaluations; and, c) no difference between self- and student evaulations. Clinical educators in the first cohort demonstrated significantly higher SECT subscale scores (effect size >0.42) than their colleagues. Age, gender, teaching qualification, and years practicing or years as a clinical educator were not associated with clinical educator OCTQ scores or the SECT subscales.

Conclusions

Targeted professional development directed towards fostering self-efficacy may provide an avenue for engaging those clinical educators whose self-efficacy is low and/or those who did not receive high student evaluations. Given there is no gold standard measure of clinical teaching quality, educators should engage with multiple sources of feedback to benchmark their current performance level, and identify opportunities to improve. Student and self-evaluations using the OCTQ and evaluation of self-efficacy using the SECT, are useful tools for inclusion in a whole-of-system approach to evaluation of the clinical learning environment.
Views of advanced cancer patients, families, and oncologists on initiating and engaging in advance care planning: a qualitative study
Authors: Toguri James Thomas , Grant-Nunn Lindsay , Urquhart Robin
Published: September 2020

Background: Advance care planning (ACP) is a process by which patients reflect upon their goals, values and beliefs to allow them to make decisions about their future medical treatment that align with their goals and values, improving patient-centered care. Despite this, ACP is underutilized and is reported as one of the most difficult processes of oncology. Aims: To 1) explore patients’ and families’ understanding, experience and reflections on ACP, as well as what they need from their physicians during the process; 2) explore physicians’ views of ACP, including their experiences with initiating ACP and views on ACP training. Design and setting: Qualitative descriptive study in Nova Scotia, Canada with oncologists, advanced cancer out-patients and their family members. Methods: Semi-structured interviews with advanced cancer out-patients and their family members (n=4 patients, 4 family members) and oncologists (n=10) were conducted; each participant was recruited separately. Data were analyzed using constant comparative analysis, which entailed coding, categorizing, and identifying themes recurrent across the datasets. Results: Themes were identified from the patient / family and oncologist groups, four and five respectively. Themes from patients / families included: 1) positive attitudes towards ACP; 2) healthcare professionals (HCPs) lack an understanding of patients’ and families’ informational needs during the ACP process; 3) limited access to services and supports; and 4) poor communication between HCPs. Themes from oncologists included: 1) initiation of ACP discussions; 2) navigating patient-family dynamics; 3) limited formal training in ACP; 4) ACP requires a team approach; and 5) lack of coordinated systems hinders ACP. Conclusion: Stakeholders believe ACP for advanced cancer patients is important. Patients and families desire earlier and more in-depth discussion of ACP, additional services and supports, and improved communication between their HCPs. In the absence of formal training or guidance, oncologists have used clinical acumen to initiate ACP and a collaborative healthcare team approach.
Influence of X ray computed tomography (CT) exposure and reconstruction parameters on positron emission tomography (PET) quantitation.
Authors: Shon Ivan Ho , Reece Christopher , Hennessy Thomas , Horsfield Megan , McBride Bruce
Published: September 2020

Background: The CT of PET CT provides diagnostic information, anatomic localisation and attenuation correction (AC). When only AC is required very lose dose CT is desirable. CT iterative reconstruction (IR) improves image quality with lower exposures however there is little data on very low dose IR CT for AC of PET. This work assesses the impact of CT exposure and reconstruction algorithm on PET voxel values.Method: An anthropomorphic torso phantom was filled with physiologically typical [18]F concentrations in heart, liver and background compartments. A 17mm diameter right lung “tumour” filled with [18]F was included (surrounding lung contained no 18[F]). PET was acquired followed by 24 CT acquisitions with varying CT exposures (15 - 50mAs, 80 – 120kVp, pitch 0.671 or 0.828). Each CT was reconstructed twice using filtered back projection (FBP) or IR and these used for AC of PET. The reference PET reconstruction (RR) used CT acquired at 50mAs, 120kVp, pitch 0.828, IR, all others were test PET reconstructions (TR). Regions of interest (ROIs) were drawn in liver, soft tissue and over “tumour” on each TR and compared with the RR. Voxel values in each TR were compared to the RR using a paired t-test and by calculating which and what proportion of voxels in each TR differed by a quantitatively significant difference (QSD) from the RR.Results: TRs reconstructed using lower dose CTs underestimated mean and maximum ROI activity relative to the RR; greater with IR than FBP. Once CT dose index (CTDI) increased to 1 mGy, differences were less than QSD. On voxel analysis all TRs were significantly different to the RR (p <0.0001). TRs reconstructed at the lowest CT exposure with IR had 6% of voxels that differed by greater than QSD. Differences were reduced with increasing CTDI and FBP reconstruction. Voxels which exceeded the QSD were spatially localised to regions of high activity, interfaces between different attenuation and areas of CT beam hardening.Conclusions: Very low dose CT exposures are feasible for accurate PET AC. Scanner and reconstruction specific validation should be employed prior very low dose CT AC for PET.
Housing conditions, level of feeding and presence of antibiotics in the feed shape rabbit cecal microbiota
Authors: Velasco-Galilea María , Guivernau Miriam , Piles Miriam , Viñas Marc , Rafel Oriol , Sánchez Armand , Ramayo-Caldas Yuliaxis , González-Rodríguez Olga , Sánchez Juan P.
Published: September 2020

Background: the effect of the production environment and different management practices in rabbit cecal microbiota remains poorly understood. While previous studies have proved the impact of the age or the feed composition, research in the housing conditions and other animal management aspects, such as the presence of antibiotics in the feed or the level of feeding, is still needed. Characterization of microbial diversity and composition of growing rabbits raised under different conditions could help better understand the role these practices play in cecal microbial communities and how it may result in different animal performance.Results: four hundred twenty-five meat rabbits raised in two different facilities, fed under two feeding regimes (ad libitum or restricted) with feed supplemented or free of antibiotics, were selected for this study. A 16S rRNA gene-based assessment through the MiSeq Illumina sequencing platform was performed on cecal samples collected from these individuals at slaughter. Different univariate and multivariate approaches were conducted to unravel the influence of the different factors on microbial alpha diversity and composition at phylum, genus and OTU taxonomic levels. The animals raised in the facility harboring the most stable environmental conditions had greater, and less variable, microbial richness and diversity. Bootstrap univariate analyses of variance and sparse partial least squares-discriminant analyses endorsed that farm exerted the largest influence on rabbit microbiota since the relative abundances of many taxa were found differentially represented between both facilities at all taxonomic levels characterized. Furthermore, only five OTUs were needed to achieve a perfect classification of samples according to the facility where animals were raised. The level of feeding and the presence of antibiotics did not modify the global alpha diversity but had an impact on some bacteria relative abundances, albeit in a small number of taxa compared with farm, which is consistent with the lower sample classification power according to these factors achieved using microbial information.Conclusions: this study reveals different degrees of influence attributable to environment and animal management. It highlights the importance of offering a controlled breeding environment that reduces differences in microbial cecal composition that could be causative of different animal performance.
Effect of dapsone alone and in combination with intracellular antibiotics against the biofilm form of B. burgdorferi 
Authors: Horowitz Richard Ira , Murali Krithika , Gaur Gauri , Freeman Phyllis R. , Sapi Eva
Published: September 2020

Objective: Lyme disease is a tick-borne, multisystemic disease caused by Borrelia burgdorferi. Standard treatments for early Lyme disease include short courses of oral antibiotics but relapses often occur after discontinuation of treatment. Several studies have suggested that ongoing symptoms may be due to a highly antibiotic resistant form of B. burgdorferi called biofilms. Our recent clinical study reported the successful use of an intracellular mycobacterium persister drug used in treating leprosy, diaminodiphenyl sulfone (dapsone), in combination therapy for the treatment of Lyme disease. In this in vitro study, we evaluated the effectiveness of dapsone individually and in combination with cefuroxime and/or other antibiotics with intracellular activity including doxycycline, rifampin, and azithromycin against Borrelia biofilm forms utilizing crystal violet biofilm mass, and dimethyl methylene blue glycosaminoglycan assays combined with Live/Dead fluorescent microscopy analyses. Results: Dapsone, alone or in various combinations with doxycycline, rifampin and azithromycin produced a significant reduction in the mass and protective glycosaminoglycan layer and overall viability of B. burgdorferi biofilm forms. This in vitro study strongly suggests that dapsone combination therapy could represent a novel and effective treatment option against the biofilm form of B. burgdorferi.
Cross-sectional survey on impact of paediatric COVID-19 among Italian paediatricians: report from the SIAIP rhino-sinusitis and conjunctivitis committee.
Authors: Diaferio Lucia , Parisi Giuseppe Fabio , Brindisi Giulia , Indolfi Cristiana , Marchese Giuseppe , Ghiglioni Daniele Giovanni , Zicari Anna Maria , Marseglia Gian Luigi , Giudice Michele Miraglia del
Published: September 2020

BackgroundThere is ample evidence that COVID-19 is significantly less severe in children than in adults and asthma and allergy, the most common chronic disorders in children, are not included in the top 10 comorbidities related to COVID-19 fatalities. Nevertheless, concerns about asthma and allergy are still high.. In order to evaluate the impact of paediatric COVID-19 among Italian paediatricians, we sent a 20-questions anonymous internet-based survey to 250 Italian paediatricians with particular address to allergic symptoms and those affecting the upper airwaysMethodsThe questionnaire was conceived and pretested in April 2020, by a working group of experts of the Italian Paediatric Society for Allergy and Immunology (SIAIP), and structured into different sections of 20 categorized and multiple choice questions. The first part included questions about epidemiological data follows by a second part assessing the way to manage a suspected COVID-19 infection and personal experiences about that. The third part concerned questions about patients’ clinical characteristics and clinical manifestations.The survey was emailed once between April and mid-May 2020. ResultsA total 99 participants had participated in our survey and provided responses to our electronic questionnaire. The distribution of patients reported per month varies significantly according to the geographical area (P=0.02). Data confirmed that in the North part of Italy the rate of patients referred is higher than in the rest of Italy. Almost all respondents (98%) reported caring for up to a maximum of 10 infected children and the last 2% more than twenty. Among these patients, according to the 75% of responders, a maximum rate of 20% were affected by allergic rhino-conjunctivitis and in particular in the North of Italy while in the Centre and in the South there was a higher incidence (P=0.09). Almost the same applies for asthma, 83% of responders declared that up to a maximum of 20% of affected children were asthmatic, from 20% to 40% for the 13,5% of responders and from 40% to 60% for the last 3,5%. As for the allergic conjunctivitis also for asthma, we found a higher incidence in the Centre and in South than in the North (P=0.03).
Pseudomonas aeruginosa bloodstream infection at a tertiary referral hospital for children
Authors: Dame Joycelyn Assimeng , Beylis Natalie , Nuttall James , Eley Brian
Published: September 2020

Background This study describes the disease burden, clinical characteristics, antibiotic management, impact of multidrug resistance and outcome of Pseudomonas aeruginosa bloodstream infection (PABSI) among children admitted to a tertiary referral hospital for children in Cape Town, South Africa. Methods A retrospective descriptive study was conducted at a paediatric referral hospital in Cape Town, South Africa. Demographic and clinical details, antibiotic management and patient outcome information were extracted from medical and laboratory records. Antibiotic susceptibility results of identified organisms were obtained from the National Health Laboratory Service database.Results The incidence risk of PABSI was 5.4 (95% CI: 4.34-6.54) PABSI episodes / 10,000 hospital admissions and the most common presenting feature was respiratory distress, 34/91 (37.4%). Overall, 69/91 (75.8%) of the PA isolates were susceptible to all antipseudomonal antibiotic classes evaluated. Fifty (54.9%) of the PABSI episodes were treated with appropriate empiric antibiotic therapy. The mortality rate was 24.2% and in multivariable analysis, empiric antibiotic therapy to which PA isolates were not susceptible, infections present on admission, and not being in the intensive care unit at the time that PABSI was diagnosed were significantly associated with 14-day mortality.Conclusions PABSI caused appreciable mortality, however, appropriate empiric antibiotic therapy was associated with reduced 14-day mortality. Keywords: Pseudomonas aeruginosa bloodstream infection, children, Sub-Saharan Africa.
Maternal vaccinations coverage and reasons for non-compliance - A cross-sectional observational study
Authors: Drezner David , Youngster Michal , Klainer Hodaya , Youngster Ilan
Published: September 2020

Background: Maternal influenza and pertussis vaccinations have been proven safe and effective in reducing maternal and infant morbidity and mortality. Though recommended, not all pregnant women receive these important vaccines. We aimed to evaluate the vaccine coverage of maternal immunization in pregnancy for seasonal influenza and acellular pertussis and elucidate the reasons for non-vaccination among pregnant women. The secondary objective was to describe factors that affect vaccine uptake. Methods: A cross sectional observational study using anonymous questionnaires distributed to women in the maternity ward or pregnant women hospitalized in the high-risk ward, between Nov 2017 and June 2018, In an Israeli tertiary hospital.Results: Of 321 women approached, 313 were eligible, with a total of 290 women completing the questionnaire (92.6%). We found a 75.9% (95% CI 71-81) and 34.5% (95% CI 29-40) vaccination rate for pertussis and influenza vaccines, respectively. The most prominent reason for not receiving the pertussis vaccine was being under-informed (24%). Influenza vaccine was not received mainly due to concerns about vaccine efficacy (28%). Other factors influencing vaccine uptake included education, prior childbirth and vaccine recommendations made by the provider.Conclusion: Although maternal vaccination of pertussis and influenza is officially recommended, vaccine uptake is suboptimal. Our study suggests a central role for medical providers in diminishing the concerns about safety and efficacy, and presents novel factors influencing compliance rates, like seasonality and number of prior births.
Transplanted Embryonic Retinal Stem Cells have the Potential to Repair the Injured Retina in Mice
Authors: Feng Xia , Chen Peng , Zhao Xin , Wang Jing , Wang Hong
Published: September 2020

Background: Stem cell transplantation has been reported as one of the promising strategies to treat retinal degenerative diseases, but this field is so complicated and still relatively new. This study investigated the potential role of transplantation of the embryo-derived retina stem cells (RSCs) into the vitreous cavity in repairing the damaged retina in mice.Methods: RSCs were isolated from Kunming mice E17 embryonic retina and ciliary body tissues. RSCs were cultured, differentiated, and labeled with 5-bromo-2’-deoxyuridin (BrdU). Retinal injury was induced in left eyes in male Kunming mice by ring clamping of the optic nerve. The 6th-generation of BrdU-labeled RSCs were transplanted into the damaged retina by the intravitreal injection, and saline injected eyes were used as the control. Hematoxylin and eosin histological staining, and BrdU, Nestin and Pax6 immunostaining were performed.Results: Embryo-derived RSCs were identified by the positive stains of Pax6 and Nestin. BrdU incorporation was detected in most of RSCs. The damaged retina showed diffuse edema, disordered and loose-arranged morphological changes in all retinal layers. In the damaged retina with RSCs transplantation, the positive staining for BrdU, Pax6 and Nestin were revealed on the retinal surface. Notably, a small amount of RSCs migrated into the retinal ganglion cell layer and inner nuclear.Conclusions: Embryonic RSCs have similar characteristics to neural stem cells. Transplantation of RSCs by intravitreal injection would be able to repair the damaged retina.
The effect of hearing protection devices on speech intelligibility of Persian employees
Authors: Karami Mina , Aliabadi Mohsen , Golmohammadi Rostam , Nahrani Morteza Hamidi
Published: September 2020

Objective: This study aimed to investigate the effect of hearing protection devices (HPDs) on speech intelligibility in Persian work environments. Three current earmuffs and three earplugs and one of the prototypes of molded earplug were tested on 15 male subjects which were randomly selected. The noise reduction of HPDs was measured based on the Real Ear Attenuation at Threshold (REAT) method. Speech intelligibility during using HPDs was determined based on the speech discrimination score (SDS) at two signal to noise (S/N) ratios (0 and +5). Data were analyzed using SPSS 22.Results: The actual to nominal noise reduction rating values were from 47% to 84% for HPDs. At two S/N ratios, no significant differences were observed in speech intelligibility using HPDs (p >0.05). However, at S/N ratio=0, the speech intelligibility descriptively has been improved by using common earmuffs up to 9.07 %. There was a significant difference up to 21.27% in speech intelligibility for proposed molded earplugs at S/N ratio=0 (p <0.05). Increase the HPDs' noise attenuation values lead to increase interference in the speech (p <0.05). The HPDs with the minimum required noise attenuation while maintaining acceptable speech ineligibility should be worn by employees exposed to medium noise levels.
The asynchronous growth and movement reconstruction of the early molting animals
Authors: Lan Tian , Medeiros Daniel Meulemans
Published: September 2020

Epithelium is one of the basic types of animal tissue, and forms tissue boundaries that act as physical barriers to separate adjacent cell clusters. However, tissue boundaries at cellular resolutions can hardly be found in the fossil record. Here we focus on the growth and movement patterns of early Ecdysozoans by quantifying cell-level forces in the epithelium of two worms from the early Cambrian and Ordovician period. The arrangement of the epithelium cells (that do not necessarily represent biological cells) separating the body rings of these early Ecdysozoans indicates precise morphological patterning at the cellular level was established in the early Cambrian. The force distribution patterns on the body ring further suggest that the boundary cells helped maintain a pressure gradient between the rings, consistent with a role in movement. Finally, the active tension field of the worms plates throughout their ontogeny, and steady state of their epithelium cells, indicate these molting animals employed an asynchronous growth pattern in their epithelium.
Surgical Lobectomy of Pulmonary Arteriovenous Malformations in a Patient with Presentations Regarded as Sequela of Tuberculosis: A Case Report
Authors: Teng Peng , Li Weidong , Ni Yiming
Published: September 2020

Background: Pulmonary arteriovenous malformations are uncommon conditions of abnormal communications between pulmonary arteries and veins, which are most commonly congenital in nature. Although such condition is not extremely rare, it is a challenge to the differential diagnosis of pulmonary problems such as hypoxemia and pulmonary lesions.Case presentation: We report a meaningful case of a 23-year-old male presented with elevated hemoglobin (23.0 g/dl) on admission. Physical examination revealed cyanosis, digital clubbing and low oxygen saturation on room air. The patient was initially diagnosed as polycythemia vera while the subsequent result of bone marrow aspiration was negative. During further assessment, pulmonary arteriovenous malformations were detected by CT pulmonary angiography. Lobectomy was successfully performed with significant increase in oxygen saturation from 86% to 98%. The hemoglobin decreased to almost normal level of 14.9 g/dl three months after surgery and the patient had been followed up for nearly 5 years.Conclusions: Pulmonary arteriovenous malformations should be suspected in patients with central cyanosis, digital clubbing, polycythemia, pulmonary lesion and without cardiac malformations. Embolization or surgery is strongly recommended to reduce the risks caused by pulmonary arteriovenous malformations.
Integrating Bayesian Inference with Scanning Probe Experiments for Robust Identification of Surface Adsorbate Configurations
Authors: Järvi Jari , Alldritt Benjamin , Krejčí Ondřej , Todorovic Milica , Liljeroth Peter , Rinke Patrick
Published: September 2020

Controlling the properties of organic/inorganic materials requires detailed knowledge of their molecular adsorption geometries. This is often unattainable, even with current state-of-the-art tools. Visualizing the structure of complex non-planar adsorbates with atomic force microscopy (AFM) is challenging, and identifying it computationally is intractable with conventional structure search. In a fresh approach, we propose to integrate cross-disciplinary tools for a robust and automated identification of 3D adsorbate configurations. We employ Bayesian optimization with first-principles simulations for accurate and unbiased structure inference of multiple adsorbates. The corresponding AFM simulations then allow us to fingerprint adsorbate structures appearing in AFM experimental images. In the instance of bulky (1S)-camphor adsorbed on the Cu(111) surface, we found three matching AFM image contrasts, which allowed us to correlate experimental image features to distinct cases of molecular adsorption.
Machine Learning-driven Multiscale Modeling Reveals Lipid-Dependent Dynamics of RAS Signaling Proteins
Authors: Ingolfsson Helgi , Neale Chris , Carpenter Timothy , Shrestha Rebika , Lopez Cesar , Tran Timothy , Oppelstrup Tomas , Bhatia Harsh , Stanton Liam , Zhang Xiaohua , Sundram Shiv , Natale Francesco Di , Agarwal Animesh , Dharuman Gautham , Schumacher Sara Kokkila , Turbyville Thomas , Gulten Gulcin , Van Que , Goswami Debanjan , Jean-Francios Frantz , Agamasu Constance , Chen De , Hettige Jeevapani , Travers Timothy , Sarkar Sumantra , Surh Michael , Yang Yue , Moody Adam , Liu Shusen , Essen Brian Van , Voter Arthur , Ramanathan Arvind , Hengartner Nicolas , Simanshu Dhirendra , Stephen Andrew , Bremer Peer-Timo , Gnanakaran S , Glosli James , Lightstone Felice , McCormick Frank , Nissley Dwight , Streitz Frederick
Published: September 2020

RAS is a signaling protein associated with the cell membrane that is mutated in 30% of human cancers. RAS signaling has been proposed to be regulated by dynamic heterogeneity of the cell membrane. Investigating such a mechanism requires near-atomic detail at macroscopic temporal and spatial scales, which is not possible with conventional computational or experimental techniques. We demonstrate here a multiscale simulation infrastructure that uses machine learning to create a scale-bridging ensemble of over 100,000 simulations of active wild-type KRAS on a complex, asymmetric membrane. Initialized and validated with experimental data (including a new structure of active wild-type KRAS), these simulations represent a substantial advance in the ability to characterize RAS-membrane biology. We report distinctive patterns of local lipid composition that correlate with interfacially promiscuous RAS multimerization. These lipid fingerprints are coupled to RAS dynamics, predicted to influence effector binding, and therefore may be a mechanism for regulating cell signaling cascades.