bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantification of Natural Growth of Two Strains of Mycobacterium Marinum for Translational Antituberculosis Drug Development
Authors: Van Wijk Rob C. , van der Sar Astrid M. , Krekels Elke H.J. , Verboom Theo , Spaink Herman P. , Simonsson Ulrika S.H. , van der Graaf Piet H. 
Published: April 2020

The zebrafish infected with Mycobacterium marinum (M. marinum) is an attractive tuberculosis disease model, showing similar pathogenesis to Mycobacterium tuberculosis (M. tuberculosis) infections in humans. To translate pharmacological findings from this disease model to higher vertebrates, a quantitative understanding of the natural growth of M. marinum in comparison to the natural growth of M. tuberculosis is essential. Here, the natural growth of two strains of M. marinum, E11 and MUSA, is studied over an extended period using an established model‐based approach, the multistate tuberculosis pharmacometric (MTP) model, for comparison to that of M. tuberculosis. Poikilotherm‐derived strain E11 and human‐derived strain MUSA were grown undisturbed up to 221 days and viability of cultures (colony forming unit (CFU)/mL) was determined by plating at different time points. Nonlinear mixed effects modeling using the MTP model quantified the bacterial growth, the transfer among fast, slow, and non‐multiplying states, and the inoculi. Both strains showed initial logistic growth, reaching a maximum after 20–25 days for E11 and MUSA, respectively, followed by a decrease to a new plateau. Natural growth of both E11 and MUSA was best described with Gompertz growth functions. For E11, the inoculum was best described in the slow‐multiplying state, for MUSA in the fast‐multiplying state. Natural growth of E11 was most similar to that of M. tuberculosis, whereas MUSA showed more aggressive growth behavior. Characterization of natural growth of M. marinum and quantitative comparison with M. tuberculosis brings the zebrafish tuberculosis disease model closer to the quantitative translational pipeline of antituberculosis drug development.
A pragmatic study of mid‐mixture insulin and basal insulin treatment in patients with type 2 diabetes uncontrolled with oral antihyperglycaemic medications: A lesson from real‐world experience
Authors: Zhang Xiaomei , Ma Yujin , Chen Hong , Lou Ying , Ji Linong , Chen Lulu 
Published: April 2020

AbstractBackgroundChinese guidelines for the treatment of type 2 diabetes (T2D) recommend basal or premixed insulins as insulin starters after failed oral antihyperglycaemic medication (OAM). This pragmatic study compared effectiveness and safety of add‐on basal insulin analog (BI) and mid‐mixture insulin analog (MMI; 50:50 premixed insulin) as starter insulin regimens in Chinese patients with T2D in a real‐world setting.Materials and MethodsThis was a multicentre, open‐label, randomized, parallel, pragmatic trial. Patients receiving OAMs were randomized 1:1 to BI (n = 410) or MMI (n = 404) for 24 weeks. Insulin titration and OAM adjustment were determined by investigators following usual standard‐of‐care. The primary outcome was change in glycated haemoglobin (HbA1c) from baseline.ResultsLeast‐squares mean changes in HbA1c from baseline to week 24 were −2.00% and −2.15% for BI and MMI groups, respectively (P = .13). The MMI group demonstrated a greater reduction in concomitant OAM therapies used than BI group (53.8% vs. 35.3%, respectively; P < .001). Very limited daily insulin dose increments were observed from baseline to week 24 in both BI and MMI groups (2.5 U/day and 1.8 U/day, respectively). Although both insulin analogs were well‐tolerated without severe hypoglycaemia, small weight gains were seen with both treatments. Higher total hypoglycaemia rates were noticed with the MMI group, while nocturnal hypoglycaemia events were comparable.ConclusionsIn real‐world settings, BI and MMI provided similar improvement in glucose control without conceding hypoglycaemia. The BI group received a greater number of OAMs in real‐world settings. Limited insulin dose titration was observed, while more adjustments occurred with OAM usage.
The worldwide impact of urbanisation on avian functional diversity
Authors: Sol Daniel , Trisos Christopher , Múrria Cesc , Jeliazkov Alienor , González‐Lagos Cesar , Pigot Alex L. , Ricotta Carlo , Swan Christopher M. , Tobias Joseph A. , Pavoine Sandrine 
Published: April 2020

AbstractUrbanisation is driving rapid declines in species richness and abundance worldwide, but the general implications for ecosystem function and services remain poorly understood. Here, we integrate global data on bird communities with comprehensive information on traits associated with ecological processes to show that assemblages in highly urbanised environments have substantially different functional composition and 20% less functional diversity on average than surrounding natural habitats. These changes occur without significant decreases in functional dissimilarity between species; instead, they are caused by a decrease in species richness and abundance evenness, leading to declines in functional redundancy. The reconfiguration and decline of native functional diversity in cities are not compensated by the presence of exotic species but are less severe under moderate levels of urbanisation. Thus, urbanisation has substantial negative impacts on functional diversity, potentially resulting in impaired provision of ecosystem services, but these impacts can be reduced by less intensive urbanisation practices.
Dynamics of a human‐modified tropical peat swamp forest revealed by repeat lidar surveys
Authors: Wedeux Béatrice , Dalponte Michele , Schlund Michael , Hagen Stephen , Cochrane Mark , Graham Laura , Usup Aswin , Thomas Andri , Coomes David 
Published: April 2020

AbstractTropical peat swamp forests (PSFs) are globally important carbon stores under threat. In Southeast Asia, 35% of peatlands had been drained and converted to plantations by 2010, and much of the remaining forest had been logged, contributing significantly to global carbon emissions. Yet, tropical forests have the capacity to regain biomass quickly and forests on drained peatlands may grow faster in response to soil aeration, so the net effect of humans on forest biomass remains poorly understood. In this study, two lidar surveys (made in 2011 and 2014) are compared to map forest biomass dynamics across 96 km2 of PSF in Kalimantan, Indonesia. The peatland is now legally protected for conservation, but large expanses were logged under concessions until 1998 and illegal logging continues in accessible portions. It was hypothesized that historically logged areas would be recovering biomass while recently logged areas would be losing biomass. We found that historically logged forests were recovering biomass near old canals and railways used by the concessions. Lidar detected substantial illegal logging activity—579 km of logging canals were located beneath the canopy. Some patches close to these canals have been logged in the 2011–2104 period (i.e. substantial biomass loss) but, on aggregate, these illegally logged regions were also recovering. Unexpectedly, rapid growth was also observed in intact forest that had not been logged and was over a kilometre from the nearest known canal, perhaps in response to greater aeration of surface peat. Comparing these results with flux measurements taken at other nearby sites, we find that carbon sequestration in above‐ground biomass may have offset roughly half the carbon efflux from peat oxidation. This study demonstrates the power of repeat lidar survey to map fine‐scale forest dynamics in remote areas, revealing previously unrecognized impacts of anthropogenic global change.
Understanding minimum and ideal factor levels for participation in physical activities by people with haemophilia: An expert elicitation exercise
Authors: Martin Antony P. , Burke Tom , Asghar Sohaib , Noone Declan , Pedra Gabriel , O'Hara Jamie 
Published: April 2020

AbstractIntroductionThe benefits of physical activity (PA) for people with haemophilia (PWH) may include improvements in joint, bone and muscle health. However, the factor VIII activity level required to avoid a bleeding episode associated with PA is unknown.AimTo elicit the opinion of clinical experts on the minimum level and ideal factor VIII activity (‘level’) required to avoid a bleeding episode during participation in different types of PA for PWH.MethodsBased on the 2017 National Hemophilia Foundation PA descriptions, clinical experts estimated a minimally acceptable and an ideal factor level at which a bleed could be avoided. The uncertainty around estimates was quantified using an approach to construct a probability distribution to represent expert opinion.ResultsMinimum and ideal factor level increased with higher risk PA, whether or not joint morbidity was present, as did the experts' uncertainty in their estimates (ie the range between lowest and highest estimates for minimum and ideal levels). Mean minimum levels ranged from 4% to 48% for low to high risk for people without joint morbidity, and from 7% to 47% for those with joint morbidity. For ideal factor levels, corresponding figures were 9%‐52% and 12%‐64%, respectively.ConclusionTo support a patient‐centric outcome, expert opinion indicates that the clinical norm of 0.01 IU/mL (1%) trough level is insufficient. It is anticipated that introducing a more targeted approach to meet the needs of patients who are increasingly physically active will benefit patients further in addition to recent treatment advances.
Mechanical thrombectomy for emergent large vessel occlusion: an Australian primary stroke centre workflow analysis
Authors: Tiu Jeigh , Watson Tayler , Clissold Ben 
Published: April 2020

AbstractBackgroundTime to successful reperfusion is a critical prognostic factor for acute ischaemic stroke. Mechanical thrombectomy has become the gold standard treatment for emergent large vessel occlusion stroke. The timely delivery of this highly specialised procedure to patients outside of metropolitan centres presents a dilemma of inequity, with limited workflow data hindering benchmarking and service optimisation.AimsTo analyse key stroke treatment time parameters from a primary stroke centre existing in a regional centre within a hub‐and‐spoke delivery model in Victoria, Australia.MethodsRetrospective cohort study of patients transferred from a regional primary stroke centre to a metropolitan comprehensive stroke centre for mechanical thrombectomy between July 2016 and December 2018. Time workflow analysis was conducted from symptom onset to primary stroke centre departure.ResultsA total of 55 patients was included in this study with an average age of 70.2 years. Median National Institutes of Health Stroke Scale score on admission was 13 (interquartile range (IQR) 7–17). Median pre‐hospital time was 68 min (IQR 56–137) and median door‐in‐door‐out time was 120.5 min (IQR 98–150), constituting 36.1% and 63.9% of total median time from symptom onset to primary stroke centre departure (188.5 min) respectively. There were no significant differences across observed cohort characteristics under linear regression analysis.ConclusionProtracted pre‐hospital and primary stroke centre workflow times can delay effective treatment for patients with acute ischaemic stroke in regional areas. A systems‐level approach to streamlining processes in these key areas is required to bridge this inequity in best practice care.
Does the pre‐emptive administration of paracetamol or ibuprofen reduce trans‐ and post‐operative pain in primary molar extraction? A randomized placebo‐controlled clinical trial
Authors: Santos Pablo Silveira , Massignan Carla , de Oliveira Elisa Varela , Miranda Santana Carla , Bolan Michele , Cardoso Mariane 
Published: April 2020

AbstractBackgroundThere is no consensus whether the pre‐emptive administration of analgesics reduces trans‐ and post‐operative pain in primary molar extraction.AimInvestigate whether the pre‐emptive administration of ibuprofen and paracetamol reduces trans‐ and post‐operative pain on primary molars extraction compared to placebo.DesignA parallel, placebo‐controlled, triple‐blind, randomized clinical trial was conducted. Forty‐eight children who needed primary molar tooth extraction were selected and treated under local anaesthesia and pre‐emptive administration of placebo or analgesics. Self‐reported pain was evaluated during the anaesthesia, extraction, and 2, 6, and 24 hours of post‐operative period, using a visual analogue scale (VAS). Children's baseline anxiety, behaviour during the procedure, parents' anxiety, and post‐operative analgesia were also assessed. Data analysis included descriptive statistics and multiple linear regression.ResultsNo association was found between the use of pre‐emptive analgesic and lower scores of trans‐ and post‐operative pain compared to placebo. Children who presented negative behaviour reported greater pain during anaesthesia (P = .04) regardless of pre‐emptive analgesia group. Children from the placebo group were more likely to need post‐operative analgesia at 2 hours of follow‐up (P = .03).ConclusionThe pre‐emptive administration of analgesics did not significantly reduce trans‐ and post‐operative pain in children after primary molars extraction.
Treatment of glaucoma by prostaglandin agonists and beta‐blockers in combination directly reduces pro‐fibrotic gene expression in trabecular meshwork
Authors: Tejwani Sushma , Machiraju Praveen , Nair Archana Padmanabhan , Ghosh Anuprita , Das Raunak Kumar , Ghosh Arkasubhra , Sethu Swaminathan 
Published: April 2020

AbstractProstaglandin analogues (PG), beta‐blockers (BB) or their combination (PG+BB) are used primarily to reduce the intraocular pressure (IOP) pathologically associated with glaucoma. Since, fibrosis of the trabecular meshwork (TM) is a major aetiological factor in glaucoma, we studied the effect of these drugs on fibrosis‐associated gene expression in TM of primary glaucoma patients. In the present study, TM and iris of primary open‐angle (n = 32) and angle‐closure (n = 37) glaucoma patients were obtained surgically during trabeculectomy and categorized based on the type of IOP‐lowering medications use as PG, BB or PG+BB. mRNA expression of pro‐fibrotic and anti‐fibrotic genes was quantified using qPCR in these tissues. The gene expression levels of pro‐fibrotic genes were significantly lower in PG+BB as compared to other groups. These observations and underlying signalling validated in vitro in human TM cells also showed reduced fibrotic gene and protein expression levels following PG+BB treatment. In conclusion, it is observed that PG+BB combination rather than their lone use renders a reduced fibrotic status in TM. This further suggests that IOP‐lowering medications, in combination, would also modulate fibrosis‐associated molecular changes in the TM, which may be beneficial for maintaining aqueous out‐flow mechanisms over the clinical treatment duration.
Combined effect of diabetic retinopathy and diabetic kidney disease on all‐cause, cancer, vascular and non‐cancer non‐vascular mortality in patients with type 2 diabetes: A real‐world longitudinal study
Authors: Takao Toshiko , Suka Machi , Yanagisawa Hiroyuki , Kasuga Masato 
Published: April 2020

AbstractAims/IntroductionWe assessed the relationship between diabetic retinopathy (DR) and/or diabetic kidney disease (DKD) according to their severity and all‐cause, cancer, vascular and non‐cancer non‐vascular mortality in real‐world patients with type 2 diabetes.Materials and MethodsA total of 1,902 patients with type 2 diabetes were enrolled from 1995 to 1999 and followed to 2017. At baseline, DR was diagnosed in 374 patients, DKD in 529, vision‐threatening DR in 123 and advanced DKD in 287. Patients were classified by the status of DR and DKD. Multivariate Cox regression analysis was carried out.ResultsThere were 266 deaths during a median follow‐up period of 18.6 years. Among these, 92 were from cancer, 78 were from vascular causes and 82 were from non‐cancer non‐vascular causes. DR and/or DKD predicted all‐cause, vascular and non‐cancer non‐vascular mortality, but not cancer mortality. Similarly, vision‐threatening DR and/or advanced DKD predicted all‐cause, vascular and non‐cancer non‐vascular mortality, but not cancer mortality. Hazard ratios for all‐cause, vascular and non‐cancer non‐vascular mortality were highest in the DR(+)DKD(+) group, and higher in the DR(−)DKD(+) and the DR(+)DKD(−) groups than in the DR(−)DKD(−) group. The results for vision‐threatening DR and advanced DKD were similar. The interaction for non‐cancer non‐vascular mortality, but not all‐cause and vascular mortality, between DR and DKD and between vision‐threatening DR and advanced DKD might be significant.ConclusionsDR and DKD may be jointly and independently associated with all‐cause, vascular and non‐cancer non‐vascular mortality, but not cancer mortality, according to their severity in real‐world patients with type 2 diabetes.
Endoscopic ultrasound‐guided gallbladder drainage with a combined internal and external drainage tubes for acute cholecystitis
Authors: Matsubara Saburo , Isayama Hiroyuki , Nakai Yousuke , Kawakubo Kazumichi , Yamamoto Natsuyo , Saito Kei , Saito Tomotaka , Takahara Naminatsu , Mizuno Suguru , Kogure Hirofumi , Ishizawa Takeaki , Arita Junichi , Hasegawa Kiyoshi , Koike Kazuhiko 
Published: April 2020

AbstractBackground and AimLumen‐apposing metal stent is widely used for endoscopic ultrasound‐guided gallbladder drainage (EUS‐GBD) nowadays but not approved in many countries and might be unsuitable for elective laparoscopic cholecystectomy (LC) because of its large enterocholecysto fistula. A combination of double pigtail plastic stent (DPPS) and naso‐cystic tube (NCT) could overcome these problems. The aim of this study was to estimate the efficacy and safety of this method in patients with acute cholecystitis unfit for urgent cholecystectomy both as bridge to surgery and palliation.MethodsThis was a prospective, single‐center feasibility study. EUS‐GBD was performed with a 7Fr DPPS followed by an NCT placement. NCT was removed after 1 week. LC was performed 2 or 3 months after EUS‐GBD in eligible patients. In patients who did not underwent cholecystectomy, DPPS was left in place.ResultsTwenty‐three patients were enrolled. Both technical and clinical success rates were 96% (22/23). Early adverse events rate was 13% (3/23), including one bile peritonitis, one intraperitoneal abscess, and one melena. LC was attempted in 12 patients, and conversion to open cholecystectomy was required in three (25%). Neither recurrence of cholecystitis nor late adverse event occurred during 6 months of follow up in 10 patients who did not undergo cholecystectomy.ConclusionEUS‐GBD with a combination of DPPS and NCT is considered an effective and safe technique both as bridge to surgery and palliation.
Biological clocks and incremental growth line formation in dentine
Authors: Papakyrikos Amanda M. , Arora Manish , Austin Christine , Boughner Julia C. , Capellini Terence D. , Dingwall Heather L. , Greba Quentin , Howland John G. , Kato Akiko , Wang Xiu‐Ping , Smith Tanya M. 
Published: April 2020

AbstractDentine‐ and enamel‐forming cells secrete matrix in consistent rhythmic phases, resulting in the formation of successive microscopic growth lines inside tooth crowns and roots. Experimental studies of various mammals have proven that these lines are laid down in subdaily, daily (circadian), and multidaily rhythms, but it is less clear how these rhythms are initiated and maintained. In 2001, researchers reported that lesioning the so‐called master biological clock, the suprachiasmatic nucleus (SCN), halted daily line formation in rat dentine, whereas subdaily lines persisted. More recently, a key clock gene (Bmal1) expressed in the SCN in a circadian manner was also found to be active in dentine‐ and enamel‐ secretory cells. To probe these potential neurological and local mechanisms for the production of rhythmic lines in teeth, we reexamined the role of the SCN in growth line formation in Wistar rats and investigated the presence of daily lines in Bmal1 knockout mice (Bmal1−/−). In contrast to the results of the 2001 study, we found that both daily and subdaily growth lines persisted in rat dentine after complete or partial SCN lesion in the majority of individuals. In mice, after transfer into constant darkness, daily rhythms continued to manifest as incremental lines in the dentine of each Bmal1 genotype (wild‐type, Bmal+/–, and Bmal1−/−). These results affirm that the manifestation of biological rhythms in teeth is a robust phenomenon, imply a more autonomous role of local biological clocks in tooth growth than previously suggested, and underscore the need further to elucidate tissue‐specific circadian biology and its role in incremental line formation. Investigations of this nature will strengthen an invaluable system for determining growth rates and calendar ages from mammalian hard tissues, as well as documenting the early lives of fossil hominins and other primates.
Assessment of postoperative adjuvant treatment using toceranib phosphate against adenocarcinoma in dogs
Authors: Yamazaki Hiroki , Tanaka Toshiyuki , Mie Keiichiro , Nishida Hidetaka , Miura Naoki , Akiyoshi Hideo 
Published: April 2020

AbstractBackgroundToceranib phosphate (TOC) could be made widely available for treating tumors in dogs if evidence shows that TOC inhibits recurrence after surgery.ObjectivesTo investigate how postoperative adjuvant treatment with TOC modulates the tumor microenvironment (TME), by assessing effects on angiogenic activity, tumor‐infiltrating regulatory T cells (Tregs), and intratumoral hypoxia.AnimalsNinety‐two client‐owned dogs were included: 28 with apocrine gland anal sac adenocarcinoma, 24 with small intestinal adenocarcinoma, 22 with lung adenocarcinoma, and 18 with renal cell carcinoma.MethodsRetrospective, multicenter study comparing time to progression (TTP) between 42 dogs treated by surgery and TOC and 50 dogs treated by surgery alone. Differences were analyzed in the expression of vascular endothelial growth factor receptor‐2 (VEGFR2) and the number of Foxp3+ Tregs and hypoxia‐inducible factor (HIF)‐1α+ cells in tumor tissues sampled at the first and second (recurrence) surgeries.ResultsMedian TTP for dogs treated by surgery and TOC (360 days) was higher than that for dogs treated by surgery alone (298 days; hazard ratio, 0.82; 95% confidence interval [CI], 0.65‐0.96; P = .02). In dogs treated by surgery and TOC, VEGFR2 expression and the number of Tregs and HIF‐1α+ cells were significantly lower in tissues sampled at the second surgery than in those sampled after the first surgery. In dogs treated by surgery alone, significant differences were found between samples from the 2 surgeries.Conclusions and Clinical ImportanceToceranib phosphate could prove to be a useful postoperative adjuvant treatment because of its modulation of the TME.