bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diversity of herbaceous plants and bacterial communities regulates soil resistome across forest biomes
Authors: Hu Hang‐Wei , Wang Jun‐Tao , Singh Brajesh K. , Liu Yu‐Rong , Chen Yong‐Liang , Zhang Yu‐Jing , He Ji‐Zheng 
Published: April 2018

SummaryAntibiotic resistance is ancient and prevalent in natural ecosystems and evolved long before the utilization of synthetic antibiotics started, but factors influencing the large‐scale distribution patterns of natural antibiotic resistance genes (ARGs) remain largely unknown. Here, a large‐scale investigation over 4000 km was performed to profile soil ARGs, plant communities and bacterial communities from 300 quadrats across five forest biomes with minimal human impact. We detected diverse and abundant ARGs in forests, including over 160 genes conferring resistance to eight major categories of antibiotics. The diversity of ARGs was strongly and positively correlated with the diversity of bacteria, herbaceous plants and mobile genetic elements (MGEs). The ARG composition was strongly correlated with the taxonomic structure of bacteria and herbs. Consistent with this strong correlation, structural equation modelling demonstrated that the positive effects of bacterial and herb communities on ARG patterns were maintained even when simultaneously accounting for multiple drivers (climate, spatial predictors and edaphic factors). These findings suggest a paradigm that the interactions between aboveground and belowground communities shape the large‐scale distribution of soil resistomes, providing new knowledge for tackling the emerging environmental antibiotic resistance.
Genome plasticity in response to stress inTetrahymena thermophila: selective and reversible chromosome amplification and paralogous expansion of metallothionein genes
Authors: de Francisco Patricia , Martín‐González Ana , Turkewitz Aaron P. , Gutiérrez Juan Carlos 
Published: April 2018

SummaryExtreme stress situations can induce genetic variations including genome reorganization. In ciliates likeTetrahymena thermophila, the approximately 45‐fold ploidy of the somatic macronucleus may enable adaptive responses that depend on genome plasticity. To identify potential genome‐level adaptations related to metal toxicity, we isolated threeTetrahymena thermophilastrains after an extended adaptation period to extreme metal concentrations (Cd2+, Cu2+or Pb2+). In the Cd‐adapted strain, we found a approximately five‐fold copy number increase of three genes located in the same macronuclear chromosome, including two metallothionein genes,MTT1andMTT3. The apparent amplification of this macronuclear chromosome was reversible and reproducible, depending on the presence of environmental metal. We also analysed three knockout (KO) and/or knockdown (KD) strains forMTT1 and/or MTT5. In the MTT5KD strain, we found at least two new genes arising from paralogous expansion ofMTT1, which encode truncated variants ofMTT1. The expansion can be explained by a model based on somatic recombination betweenMTT1genes on pairs of macronuclear chromosomes. At least two of the new paralogs are transcribed and upregulated in response to Cd2+. Altogether, we have thus identified two distinct mechanisms, both involving genomic plasticity in the polyploid macronucleus that may represent adaptive responses to metal‐related stress.
Laparoscopic radical cystectomy with intracorporeal ileal conduit diversion: Modified techniques and long‐term outcomes
Authors: Xu Yujie , Pan Feng , Liu Dong , Yang Xiong , Li Shuqiang , Zhang Qijun , Li Bing 
Published: April 2018

AimThe aim of the present study was to assess the efficacy and long‐term outcomes of laparoscopic radical cystectomy (LRC) with ileal conduit urinary diversion for organ‐confined bladder carcinoma, undertaken intracorporeally using our modified techniques.Patients and MethodsSeven male patients underwent LRC with intracorporeal ileal conduit diversion only using pure laparoscopic techniques.ResultsAll procedures were completed without open conversion or intraoperative complications. The surgical margins of the specimens were negative in all patients. The mean duration of surgery was 7 h (range: 6–8.5), the mean blood loss was 420 mL (range: 330–750) and the mean postoperative hospital stay was 9 days (range: 7–15). At a mean follow up of 44 months (range: 36–49), one patient developed intestinal obstruction requiring an operation after 32 months. Another developed local oncological recurrence in the posterior urethra. One patient had bilateral inguinal lymphatic metastases, and another had hydronephrosis of the right kidney without symptoms. These complications and oncological recurrences were all found after 2 years. No patient has port site metastases and distant metastases to date.ConclusionsLRC with ileal conduit diversion undertaken completely intracorporeally is a safe and feasible option for organ‐confined bladder carcinoma. Our modified techniques are helpful to simplify the procedure.
The use of glucocorticoid hormones or leucocyte profiles to measure stress in vertebrates: What’s the difference?
Authors: Davis Andrew K. , Maney Donna L. 
Published: April 2018

Abstract

Measuring stress in animals is important in many ecological, zoological and veterinary research settings. A common method is to measure plasma levels of glucocorticoid hormones (cortisol, corticosterone, hereafter CORT). Over the past decade, an alternative method has become widely popular: assessing leucocyte profiles; in other words, the heterophil‐to‐lymphocyte ratio (H/L) in birds and reptiles or the neutrophil‐to‐lymphocyte ratio (N/L) in mammals, amphibians and fish. Recent studies have shown that although both indices reliably change after acute stress, they are not always correlated at baseline, and thus are not interchangeable. This lack of correlation has led to some confusion about which of these two measures is “better”; in other words, more biologically relevant and a truer readout of stress.

In this review, we first document the dramatic expansion of the use of leucocyte profiles to assess stress over the past decade. We then review published evidence that may explain the discrepancies between leucocyte profiles and plasma CORT. We argue that these discrepancies stem from the nature of the stress reaction and the role of corticosterone (or cortisol) versus leucocytes during the stress response.

The differing roles of the two responses translate to differences in the timing of each, which is important for researchers studying either acute or chronic stress. Although plasma glucocorticoids rise within minutes of the onset of acute stress and return to baseline within 1 or 2 hr after the stressor passes, H/L or N/L ratios remain low for at least 30–60 min or sometimes more.

The temporal nature of these metrics differs also in the context of long‐term chronic stress. The glucocorticoid response wanes in repeatedly stressed animals, or those exposed to chronic environmental stress, which can often (but not always) lead to low baseline levels and more typically, an attenuated acute stress response. Meanwhile, H/L or N/L ratios appear to remain high under the same conditions.

Understanding the temporal differences in the responses should help researchers decide which metric is the better method in their particular study, or whether both would be useful for elucidating different elements of the stress response.
Evaluation of avoralstat, an oral kallikrein inhibitor, in a Phase 3 hereditary angioedema prophylaxis trial: The OPuS‐2 study
Authors: Riedl M. A. , Aygören‐Pürsün E. , Baker J. , Farkas H. , Anderson J. , Bernstein J. A. , Bouillet L. , Busse P. , Manning M. , Magerl M. , Gompels M. , Huissoon A. P. , Longhurst H. , Lumry W. , Ritchie B. , Shapiro R. , Soteres D. , Banerji A. , Cancian M. , Johnston D. T. , Craig T. J. , Launay D. , Li H. H. , Liebhaber M. , Nickel T. , Offenberger J. , Rae W. , Schrijvers R. , Triggiani M. , Wedner H. J. , Dobo S. , Cornpropst M. , Clemons D. , Fang L. , Collis P. , Sheridan W. P. , Maurer M. 
Published: April 2018

AbstractBackgroundEffective inhibition of plasma kallikrein may have significant benefits for patients with hereditary angioedema due to deficiency of C1 inhibitor (C1‐INH‐HAE) by reducing the frequency of angioedema attacks. Avoralstat is a small molecule inhibitor of plasma kallikrein. This study (OPuS‐2) evaluated the efficacy and safety of prophylactic avoralstat 300 or 500 mg compared with placebo.MethodsOPuS‐2 was a Phase 3, multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group study. Subjects were administered avoralstat 300 mg, avoralstat 500 mg, or placebo orally 3 times per day for 12 weeks. The primary efficacy endpoint was the angioedema attack rate based on adjudicator‐confirmed attacks.ResultsA total of 110 subjects were randomized and dosed. The least squares (LS) mean attack rates per week were 0.589, 0.675, and 0.593 for subjects receiving avoralstat 500 mg, avoralstat 300 mg, and placebo, respectively. Overall, 1 subject in each of the avoralstat groups and no subjects in the placebo group were attack‐free during the 84‐day treatment period. The LS mean duration of all confirmed attacks was 25.4, 29.4, and 31.4 hours for the avoralstat 500 mg, avoralstat 300 mg, and placebo groups, respectively. Using the Angioedema Quality of Life Questionnaire (AE‐QoL), improved QoL was observed for the avoralstat 500 mg group compared with placebo. Avoralstat was generally safe and well tolerated.ConclusionsAlthough this study did not demonstrate efficacy of avoralstat in preventing angioedema attacks in C1‐INH‐HAE, it provided evidence of shortened angioedema episodes and improved QoL in the avoralstat 500 mg treatment group compared with placebo.
Total 5‐mm port approach: a feasible technique for both elective and emergency laparoscopic cholecystectomy
Authors: Bender Kyle , Lewin Joel , O’Rourke Harriet , Hugh Freya C. , O’Rourke Nicholas , Hugh Thomas J. 
Published: April 2018

BackgroundThe laparoscopic approach is considered the standard of care for cholecystectomy. Attempts to minimize incisions with single site and natural orifice approaches have shown promise but also have limitations. Technological advances have facilitated decreased port size, which may have a variety of benefits. The aim of this study was to determine the feasibility of an all 5‐mm port approach for patients undergoing both elective and emergency laparoscopic cholecystectomy.MethodsA consecutive series of laparoscopic cholecystectomies at three different hospitals using all 5‐mm ports was prospectively evaluated. Recorded outcomes included operative findings, procedural difficulties, the need to extend the umbilical incision during extraction, operative time, length of stay and post‐operative complications.ResultsA total of 101 patients were included and all had a successful cholecystectomy without the need for additional ports. The umbilical incision was extended for gallbladder extraction in 29 (29%) patients. Eight (8%) patients experienced minor post‐operative complications and there were no major complications. Cholangiography was performed in 98% of cases and three patients underwent successful common bile duct exploration without requiring additional ports. In a small number of cases, there was difficulty with the quality of the view through the 5‐mm laparoscope but this was rectified by removing old or damaged laparoscopes from the circulating stock.ConclusionThis study demonstrates that laparoscopic cholecystectomy using all 5‐mm ports is both feasible and safe, and is comparable to published outcomes after conventional laparoscopic cholecystectomy. Further work is needed to determine whether this approach can also improve short‐ and long‐term outcomes.
Safe use of proton pump inhibitors in patients with cirrhosis
Authors: Weersink Rianne A. , Bouma Margriet , Burger David M. , Drenth Joost P.H. , Harkes‐Idzinga S. Froukje , Hunfeld Nicole G.M. , Metselaar Herold J. , Monster‐Simons Margje H. , van Putten Sandra A.W. , Taxis Katja , Borgsteede Sander D. 
Published: April 2018

AimsProton pump inhibitors (PPIs) belong to the most frequently used drugs, also in patients with cirrhosis. PPIs are extensively metabolized by the liver, but practice guidance on prescribing in cirrhosis is lacking. We aim to develop practical guidance on the safe use of PPIs in patients with cirrhosis.MethodsA systematic literature search identified studies on the safety (i.e. adverse events) and pharmacokinetics of PPIs in cirrhotic patients. This evidence and data from the product information was reviewed by an expert panel who classified drugs as safe; no additional risks known; additional risks known; unsafe; or unknown. Guidance was aimed at the oral use of PPIs and categorized by the severity of cirrhosis, using the Child–Turcotte–Pugh (CTP) classification.ResultsA total of 69 studies were included. Esomeprazole, omeprazole and rabeprazole were classified as having ‘no additional risks known’. A reduction in maximum dose of omeprazole and rabeprazole is recommended for CTP A and B patients. For patients with CTP C cirrhosis, the only PPI advised is esomeprazole at a maximum dosage of 20 mg per day. Pantoprazole and lansoprazole were classified as unsafe because of 4‐ to 8‐fold increased exposure. The use of PPIs in cirrhotic patients has been associated with the development of infections and hepatic encephalopathy and should be carefully considered.ConclusionsWe suggest using esomeprazole, omeprazole or rabeprazole in patients with CTP A or B cirrhosis and only esomeprazole in patients with CTP C. Pharmacokinetic changes are also important to consider when prescribing PPIs to vulnerable, cirrhotic patients.
Time to treatment is an independent prognostic factor in aggressive non‐Hodgkin lymphomas
Authors: Olszewski Adam J. , Ollila Thomas , Reagan John L. 
Published: April 2018

SummaryIn aggressive lymphomas, discrepancies in survival reported from experimental and observational studies may reflect selective non‐enrolment of high‐risk patients in trials. We examined the association between time from diagnosis to chemotherapy and overall survival in diffuse large B‐cell (DLBCL), Burkitt (BL), mantle cell (MCL) and peripheral T‐cell lymphoma (PTCL), using National Cancer Data Base records of 130 549 patients treated in 2004–2014. Across the histologies, patients who started chemotherapy within 7 days of diagnosis had more often high International Prognostic Index (IPI) or advanced‐stage disease. The discrepancy in 3‐year survival between groups treated within 7 or >30 days from diagnosis ranged from 14% in BL to 30% in MCL. After adjusting for the IPI, time to treatment was significantly associated with shorter overall survival. Using the group treated >30 days from diagnosis as reference, patients treated within 7 days had a hazard ratio of 1·38 [95% confidence interval (CI), 1·28–1·48] in DLBCL, 1·42 (95% CI, 1·22–1·66) in BL, 2·23 (95% CI, 1·79–2·78) in MCL and 1·46 (95% CI, 1·18–1·81) in PTCL. Time from diagnosis to treatment may reflect high‐risk features uncaptured by standard prognostic assessments. Clinical trials should accommodate patients who need urgent therapy to improve external validity and detect treatment effects in high‐risk groups.
Policies on bruises in premobile children: Why we need improved standards for policymaking
Authors: Bilson Andy 
Published: April 2018

AbstractThis review of the 91 English children's services departments with specific policies on bruising in premobile children found a major disjuncture between research evidence and its interpretation in guidance. Many policies require all premobile children found with a bruise to be seen urgently by a paediatrician, and in some, all bruised children are subject of a formal child protection investigation regardless of the explanations for the bruise or the views of front‐line practitioners. However, the research on bruises in premobile children on which these policies were based was found to be limited and contradictory and did not fully support the guidance given. National guidance given by the National Institute for Health and Care Excellence and many local policies state that bruising in premobile children is suggestive of physical abuse because accidental bruising is uncommon despite the only longitudinal study of bruising showing 27% of premobile children were bruised over an average of 7.6 weekly observations. The paper calls for an urgent review of these policies and guidance and improved standards for policymaking.
Beyond lifestyle interventions: exploring the potential of anti‐obesity medications in the UK
Authors: Wilding J. P. H. 
Published: April 2018

SummaryIn the UK, over one‐quarter of the adult population have obesity (body mass index ≥30 kg m−2). This has major implications for patients’ health and the National Health Service. Despite published studies showing that significant weight loss can be achieved and maintained in primary care, and guidance from the National Institute for Health and Care Excellence, weight management services are inconsistently implemented. This may be due primarily to workload and financial constraints. There is also a lack of belief that specialist weight management services and anti‐obesity medications (AOMs) are a viable alternative to bariatric surgery for long‐term maintenance of weight loss. This article discusses the challenges facing obesity management and explores the reasons for the lack of investment in AOMs in the UK to date. The aim of this article is to identify whether the newer AOMs, such as naltrexone/bupropion and liraglutide 3.0 mg, are likely to perform better in a real‐world setting than current or withdrawn AOMs. In addition, it considers whether the equitable provision of specialist weight management services and future clinical trial design could be improved to help identify those individuals most likely to benefit from AOMs and, thus, improve outcomes for people with obesity in the UK.
A mixed method evaluation of adult tier 2 lifestyle weight management service provision across a county in Northern England
Authors: Ells L. , Watson P. , Carlebach S. , O'Malley C. , Jones D. , Machaira T. , Whittaker V. , Clements H. , Walker P. , Needham K. , Summerbell C. , Coulton V. , Araujo‐Soares V. 
Published: April 2018

SummaryAdult obesity in the UK remains a public health priority. Current guidance recommends local areas provide multicomponent interventions to treat adults with overweight and obesity; however, there is currently a dearth of published evidence on the evaluation of these programmes. This study reports on a mixed method evaluation of seven tier 2 weight management programmes funded by a local authority in the North of England through their public health grant (a lifestyle multicomponent weight management programme for the treatment of adults with overweight and obesity, but not severe obesity, or obesity with severe co‐morbidities). Data collected from over 2000 participants demonstrated that the proportion of participants achieving 5% initial body weight loss was comparable to that reported in recent UK weight management trials. Two services exceeded national criteria of 30% of participants achieving 5% initial body weight loss at 12 weeks, although long term data was limited. Greater weight loss was also observed in participants aged 35–44 and those without co‐morbidities. This study provides important learning points for improvements in real world weight management services, these include: standardised data collection and management tools; staff training and communication requirements; the importance of programmes that are joined up to wider support services; and the importance of providing ongoing peer and provider support, continuous monitoring and feedback, and physical activities tailored to user needs.
1,25(OH)2D3 inhibited Th17 cells differentiation via regulating the NF‐κB activity and expression of IL‐17
Authors: Sun Dong , Luo Fei , Xing Jun‐chao , Zhang Fei , Xu Jian‐zhong , Zhang Ze‐hua 
Published: April 2018

AbstractObjectivesThe role of vitamin D (VD) in innate and adaptive immune responses to tuberculosis is still unclear. Our research was aimed to uncover the effect of VD on Th17 cells and elucidate potential molecular mechanism.Materials and methodsVDR‐deficient and wild‐type mice were used to obtain CD4 T cells. Th17 cells were induced and activated by Bacillus Calmette Guerin. Flow cytometry was used to analyse the apoptosis rate and degree of differentiation of Th17 cells in the treatment of 1,25(OH)2D3. The interaction between P65 and Rorc was determined by immunofluorescence assay, luciferase reporter assay, EMSA‐Super‐shelf assay and ChIP assay. Co‐IP assay was carried out to test the interaction between VDR and NF‐κB family proteins. qRT‐PCR and Western blot were also performed to detect the levels of P65, RORγt and IL‐17.ResultsThe Th17 cells differentiation was suppressed by 1,25(OH)2D3 in vitro. We confirmed that Rorc was a downstream gene of the transcription factor P65. VDR interacts with P105/P50, P100/P52 and P65 NF‐κB family proteins. 1,25(OH)2D3 inhibited the expression of RORγt/IL‐17 by suppressing p65 transcription factor translocating to nucleus. In vivo experiments, the expression of IL‐17 and RANKL was suppressed by 1,25(OH)2D3 by VD receptor. Moreover, 1,25(OH)2D3 suppressed the inflammatory infiltrates and inhibited the expression of P65, RORγt and IL‐17 in the spleen tissues of model mice.ConclusionsTogether, 1,25(OH)2D3 suppressed the differentiation of Th17 cells via regulating the NF‐κB activity.
A tale of two clones: Caldesmon staining in the differentiation of cutaneous spindle cell neoplasms
Authors: Beck Emily M. , Bauman Tyler M. , Rosman Ilana S. 
Published: April 2018

BackgroundWe sought to compare the sensitivity and specificity of 2 different caldesmon antibodies in differentiating leiomyosarcoma from other cutaneous spindle cell neoplasms.MethodsRepresentative cutaneous spindle cell neoplasms were identified, including leiomyosarcoma, atypical fibroxanthoma, dermatomyofibroma and spindle cell squamous cell carcinoma. Immunohistochemistry was performed with antibodies directed toward caldesmon, smooth‐muscle actin (SMA) and desmin. Sensitivity and specificity were calculated using grades from 3 independent observers.ResultsThe sensitivity of caldesmon (Ventana) was 100% (95% CI 78.2%‐100%) and the specificity was 8.3% (2.8%‐18.4%). Because this stain appeared to be non‐specific, additional testing was performed on the same set of specimens using a second caldesmon clone (H‐caldesmon, Dako), which had a sensitivity of 53.9% (25.1%‐80.8%) and specificity of 96.6% (88.1%‐99.6%). The sensitivity and specificity of SMA were 85.7% (57.2%‐98.2%) and 84.5% (72.6%‐92.7%), respectively. The sensitivity of desmin was 53.3% (26.6%‐78.7%) with a specificity of 100% (94.0%‐100%).ConclusionsThe Ventana caldesmon clone is not specific to smooth muscle, a potential pitfall to laboratories using this clone. The staining pattern, sensitivity and specificity of the Dako H‐caldesmon antibody clone are similar to results from prior studies. The sensitivity and specificity of the Dako clone support its use in smooth muscle identification as an additional marker in challenging cases.