bluuebunny/crossref_metadata_2025_split huggingface dataset:
One‐quarter of chronic hepatitis D patients reach HDV‐RNA decline or undetectability during the natural course of the disease
Authors: Palom Adriana , Sopena Sara , Riveiro‐Barciela Mar , Carvalho‐Gomes Angela , Madejón Antonio , Rodriguez‐Tajes Sergio , Roade Luisa , García‐Eliz María , García‐Samaniego Javier , Lens Sabela , Berenguer‐Hayme Marina , Rodríguez‐Frías Francisco , Hernandez‐Évole Helena , Isabel Gil‐García Ana , Barreira Ana , Esteban Rafael , Buti Maria 
Published: June 2021

SummaryBackgroundSpontaneous HDV‐RNA fluctuations, assessed by nonstandardised in‐house assays, have been reported during the course of chronic hepatitis delta (CHD).AimsTo evaluate changes in serum HDV‐RNA concentrations in untreated CHD patients and correlate these changes with other HBV markers.MethodsA total of 323 consecutive serum samples from 56 CHD patients (detectable HDV‐RNA) followed for >3 years were retested for HDV‐RNA levels by a sensitive technique using the first WHO international HDV‐RNA standard. Quantitative HBsAg, HBV‐DNA, and HBV‐RNA were also determined.ResultsMost participants were male, middle‐aged, white European, and HBeAg‐negative (82%). Almost half had liver cirrhosis and 64% were receiving nucleos(t)ide analogues. At inclusion, median‐HDV‐RNA was 5.3 (4.2‐6.5) log10IU/mL, HBsAg 4.0 (3.5‐4.3) log10IU/mL, and HBV‐DNA 1.6 (1.0‐2.6) log10IU/mL; ALT values were normal in 13 (23%). During a mean follow‐up of 5.6 (3‐16) years, 14 (25%) showed ≥2log10 HDV‐RNA decline, including 11 (20%) who spontaneously achieved undetectable HDV‐RNA. Four patients (7%) lost HBsAg, with undetectable HDV‐RNA. The remaining 42 (75%) had persistently detectable HDV‐RNA. During follow‐up, patients with a ≥2log10 HDV‐RNA decline showed a greater HBsAg drop (−0.7 ± 1.1 vs −0.09 ± 0.9 log IU/mL; P = 0.039) than those with a <2 log10 HDV‐RNA decline. Overall, ALT and HBV‐DNA levels decreased over time. There were no differences in clinical outcomes between groups.ConclusionsOne‐quarter of untreated CHD patients showed a ≥2log10 decline in HDV‐RNA and 20% reached HDV‐RNA undetectability during a mean follow‐up of 5.6 years. The decline was associated with ALT decrease. These findings have implications for designing new therapies for CHD.
Observations on the use of a pain numbing device for repetitive percutaneous sampling in sheep
Authors: Munn R , Woodward A , Beths T , Whittem T 
Published: June 2021

AimsTo evaluate the success of a commercially available analgesic device (CoolSense; Coolsense Ltd, Tel Aviv, Israel) in ameliorating pain while sampling from subcutaneous tissue cages in sheep.MethodsThe CoolSense device was used as part of a major parent study involving repetitive percutaneous sampling of subcutaneous tissue cages in seven sheep. Sampling was performed by passing a hypodermic needle through the skin and withdrawing fluid from the tissue cage. Each sheep had 10 tissue cages that were individually sampled 14 times over 74 h. The device was placed on the skin of the sampling site immediately before sampling cooling and numbing the skin. The reaction of the sheep was observed by the operators, flinching or jumping as the needle was passed through the skin was deemed to be a failure. We recorded the success or failure of the device for each needle stick. This was opportunistic data collection as part of a pharmacokinetic trial, therefore no controls were included.ResultsA total of 1655 observations were recorded and then analysed using a generalised linear mixed model. Overall, 1380 of 1655 (83.4%) observations were recorded as successfully providing analgesia. Marked inter‐occasion variability was noted with success ranging from 61.42% to 92.86% across sheep:period (approximately 140 observations each). As no controls were available, the effect of treatment could not be evaluated.Conclusions and clinical relevanceThe CoolSense device is a viable option for veterinary research and clinical applications.
Flexible use of copula‐type model for dose‐finding in drug combination clinical trials
Authors: Hashizume Koichi , Tshuchida Jun , Sozu Takashi 
Published: June 2021

AbstractIdentification of the maximum tolerated dose combination (MTDC) of cancer drugs is an important objective in phase I oncology trials. Numerous dose‐finding designs for drug combination have been proposed over the years. Copula‐type models exhibit distinctive advantages in this task over other models used in existing competitive designs. For example, their application enables the consideration of dose‐limiting toxicities attributable to one of two agents. However, if a particular combination therapy demonstrates extremely synergistic toxicity, copula‐type models are liable to induce biases in toxicity probability estimators due to the associated Fréchet–Hoeffding bounds. Consequently, the dose‐finding performance may be worse than those of other competitive designs. The objective of this study is to improve the performance of dose‐finding designs based on copula‐type models while maintaining their advantageous properties. We propose an extension of the parameter space of the interaction term in copula‐type models. This releases the Fréchet–Hoeffding bounds, making the estimation of toxicity probabilities more flexible. Numerical examples in various scenarios demonstrate that the performance (e.g., the percentage of correct MTDC selection) of the proposed method is better than those exhibited by existing copula‐type models and comparable with those of other competitive designs, irrespective of the existence of extreme synergistic toxicity. The results obtained in this study could motivate the real‐world application of the proposed method in cases requiring the utilization of the properties of copula‐type models.
Election cycles affect deforestation within Brazil's Atlantic Forest
Authors: Ruggiero Patricia G. C. , Pfaff Alexander , Nichols Elizabeth , Rosa Marcos , Metzger Jean Paul 
Published: June 2021

AbstractPolicymakers’ incentives during election campaigns can lead to decisions that significantly affect deforestation. Yet this is rarely studied. For Brazil's Atlantic Forest, a highly biodiverse tropical forest, we link federal‐and‐state as well as municipal elections to annual deforestation between 1991 and 2014. Across 2253 municipalities, those with higher deforestation see a significant rise in deforestation during federal‐and‐state election years. Municipal election years raise deforestation for locations with lower deforestation, whereas all of these increases are accentuated when there is party alignment between different levels of government. This effect of election cycles has fallen over time, to date, yet that cannot be assumed to continue. Our results highlight the need to limit opportunistic behaviors that affect natural resources and the environment with implications for biodiversity, carbon storage, and other ecosystem services.
Survival after orthotopic heart transplantation in patients with BMI > = 35 with and without diabetes
Authors: Fiedler Amy G. , Stalter Lily , Marka Nicholas , Dhingra Ravi , Hermsen Joshua L. , Smith Jason W. 
Published: June 2021

AbstractBackgroundOrthotopic heart transplant (OHT) recipients with a body mass index (BMI) > = 35 have worse survival than those with a BMI < 35. Diabetes is a risk factor for mortality. We evaluated the impact of diabetes on mortality rates after OHT in patients with a BMI > 35.MethodsPatients > 18 years who underwent OHT 2008–2017 with a BMI > = 35 were identified in the United Network for Organ Sharing (UNOS) database. Recipient and donor characteristics were compared. A Kaplan Meier analysis was performed. A multivariable Cox proportional hazards model examined the relationship between diabetes and survival. The equivalence of survival outcomes was examined by an unadjusted Cox proportional hazards model and the two one‐sided test procedure, using a pre‐specified equivalence region.ResultsPatients with diabetes were older, had a higher creatinine, lower bilirubin, fewer months on the waitlist, and the donor was less likely to be on inotropes. Kaplan‐Meier analysis showed no difference in patient survival. Recipient factors associated with an increased risk of death were increasing bilirubin and machine ventilation. Increasing ischemic time resulted in an increased hazard of death. Long‐term survival outcomes were equivalent.ConclusionsIn OHT recipients with a BMI > 35, there is no statistical difference in longterm survival in recipients with or without diabetes. These results encourage continued consideration for OHT in patients BMI > 35 with coexisting diabetes.
Use of letermovir‐valganciclovir combination as a step‐down treatment after foscarnet for ganciclovir‐resistant CMV infection in kidney transplant recipients
Authors: Rho Elena , Näf Bettina , Müller Thomas F , Wüthrich Rudolf P , Schachter Thomas , von Moos Seraina 
Published: June 2021

AbstractBackgroundLetermovir (LTV) might be an alternative treatment to nephrotoxic foscarnet (FOS) in Ganciclovir (GCV) resistant cytomegalovirus (CMV) infection. However, its efficacy in controlling active CMV viremia is unclear, as it is only approved for CMV prophylaxis in hematopoietic stem‐cell transplantation.MethodsThis case series describes 14 kidney transplant recipients (KTR) with moderate‐level GCV resistant CMV infection, treated by different step‐down strategies after initial FOS therapy: (1) Observation without antiviral follow‐up or switch to valganciclovir (VGCV) (pre‐LTV era), and (2) Switch to LTV±VGCV (LTV era).ResultsOne patient died under FOS. Thirteen patients were followed under step‐down regimens. All but two patients had ongoing CMV viremia when stopping FOS. In pre‐LTV era, 5/9 (56%) experienced a CMV breakthrough > 10 000 IU/ml calling for another course of FOS, as compared to 1/4 (25%) in the LTV era. Addition of VGCV to LTV at low‐level viral breakthrough, addressing a possible developing resistance against LTV, prevented viral surge in two patients. In the pre‐LTV era, CMV‐related death or graft loss occurred in three of nine (33%), compared to no death or graft loss in the LTV era.ConclusionA step‐down strategy combining LTV+VGCV, might allow to safely stop FOS at ongoing low‐level viremia.
A randomized controlled trial of transition from insulin pump to multiple daily injections using insulin degludec
Authors: Shah Viral N. , Akturk Halis K. , Joseph Hal , Schneider Nicole , Snell‐Bergeon Janet K. 
Published: June 2021

AbstractAimTo evaluate two methods of transition from an insulin pump to multiple daily injections (MDI) using long‐acting insulin degludec (IDeg).Materials and MethodsAfter a 1‐week run‐in period, adults with type 1 diabetes for longer than 1 year and HbA1c 48‐69 mmol/mol (6.5%‐8.5%), who had been using an insulin pump at least for 6 months, were randomly transitioned to either standard of care (discontinued insulin pump and started IDeg in 1:1 dose) or overlap (IDeg 1:1 at pump basal dose, but pump continued for the first 48 hours with a gradual basal reduction; 50% from 0‐24 hours, 75% from 24‐48 hours and then pump discontinued). Participants used blinded Dexcom G6 and the IDeg dose was not changed during the trial. Primary (% time above 180 mg/dL) and secondary (% time in 70‐180 mg/dL and below 70 mg/dL) outcomes were compared between the two groups during 7 days of randomization.ResultsAge, gender, diabetes duration and basal/bolus insulin doses were similar between patients randomized to standard of care (n = 17) or overlap (n = 13) transition. Compared with overlap transition, the standard of care group spent 4.8% more time in hyperglycaemia (least square mean 4.8% [95% CI –3.3%, 12.9%]) and 5.3% less time in range (−5.3% [−12.6%, −2.0%]), without a significant difference in hypoglycaemia (0.5% [−2.3%,3.4%]). No treatment‐related adverse events were noted in either group.ConclusionThe overlap transition method may result in a significant improvement in time‐in‐range without increasing hypoglycaemia during the first week of transition from an insulin pump to MDI using IDeg in adults with type 1 diabetes.
Carbonic anhydrase inhibitors suppress seizures in a rat model of birth asphyxia
Authors: Pospelov Alexey S. , Ala‐Kurikka Tommi , Kurki Samu , Voipio Juha , Kaila Kai 
Published: June 2021

AbstractObjectiveSeizures are common in neonates recovering from birth asphyxia but there is general consensus that current pharmacotherapy is suboptimal and that novel antiseizure drugs are needed. We recently showed in a rat model of birth asphyxia that seizures are triggered by the post‐asphyxia recovery of brain pH. Here our aim was to investigate whether carbonic anhydrase inhibitors (CAIs), which induce systemic acidosis, block the post‐asphyxia seizures.MethodsThe CAIs acetazolamide (AZA), benzolamide (BZA), and ethoxzolamide (EZA) were administered intraperitoneally or intravenously to 11‐day‐old rats exposed to intermittent asphyxia (30 min; three 7+3 min cycles of 9% and 5% O2 at 20% CO2). Electrode measurements of intracortical pH, Po2, and local field potentials (LFPs) were made under urethane anesthesia. Convulsive seizures and blood acid‐base parameters were examined in freely behaving animals.ResultsThe three CAIs decreased brain pH by 0.14–0.17 pH units and suppressed electrographic post‐asphyxia seizures. AZA, BZA, and EZA differ greatly in their lipid solubility (EZA > AZA > BZA) and pharmacokinetics. However, there were only minor differences in the delay (range 0.8–3.7 min) from intraperitoneal application to their action on brain pH. The CAIs induced a modest post‐asphyxia elevation of brain Po2 that had no effect on LFP activity. AZA was tested in freely behaving rats, in which it induced a respiratory acidosis and decreased the incidence of convulsive seizures from 9 of 20 to 2 of 17 animals.SignificanceAZA, BZA, and EZA effectively block post‐asphyxia seizures. Despite the differences in their pharmacokinetics, they had similar effects on brain pH, which indicates that their antiseizure mode of action was based on respiratory (hypercapnic) acidosis resulting from inhibition of blood‐borne and extracellular vascular carbonic anhydrases. AZA has been used for several indications in neonates, suggesting that it can be safely repurposed for the treatment of neonatal seizures as an add‐on to the current treatment regimen.
Locomotion with a twist: Aquatic beetle walks upside down on the underside of the water's surface
Authors: Gould John , Valdez Jose. W. 
Published: June 2021

AbstractWhile animals generally move through the aquatic environment by propelling themselves through the water or walking on submerged substrates, some have evolved the unique capacity to move along the water–air interface. This is because cohesive forces between water molecules cause the surface to be in tension, providing a physical substrate that can be used for support and pushed against for horizontal movement. Herein, we report on the use of the underside of the water's surface for locomotion in an unidentified Australian beetle (likely family: Hydrophilidae). Field observations revealed that the beetle was able to rest and move along the surface of an ephemeral pool inverted without penetrating the surface above. The beetle possessed a layer of trapped air along its abdomen and moved forward by walking, with deformations of the water's surface apparent each time a leg made contact. This appears to be the first visual evidence illustrating the ability of aquatic beetles to directly rest and walk on the underside of the water's surface. We propose that the air bubbles located on the abdomen and/or legs may be providing the upward force necessary for the beetle to be pushed against the underside of the water's surface. The water's surface seems to be acting as a support for the beetle, with the force needed for forward movement generated by the beetle's legs as each transition between the stance and swing phases of walking. Our work adds to the small number of observations of animals using the underside of the water's surface to move and highlights the likely importance of surface tension for locomotion on either side of the water–air interface.
An ultrasonic‐based experimental model to evaluate the setting time of endodontic sealers
Authors: Alves Thais Oliveira , Lopes Fabiane Carneiro , Yamin Paulo André , Navas Elcio Aparecido , da Cruz Filho Antonio Miranda , De‐Deus Gustavo , Sousa‐Neto Manoel Damião , Silva Ricardo Gariba 
Published: June 2021

AbstractAimTo evaluate an ultrasonic‐based experimental model (US), to assess the setting time of AH Plus®, Bio‐C Sealer® and MTA Fillapex®, and compare the results obtained with ANSI/ADA specifications (2012).MethodsTo determine the setting time according to the ANSI/ADA specification, moulds measuring 10 mm (diameter) × 2 mm (thickness) were used, and for the US tests a transducer (1 MHz) and an oscilloscope were used. Fourier‐transform infrared spectroscopy (FTIR) was used to evaluate the changes on chemical structure at the different setting times found by the US and ANSI/ADA methods. After checking the normal distribution, setting time data were analysed using unilateral analysis of variance with Tukey‐HSD post‐test to compare the methods.ResultsAH Plus® and Bio‐C Sealer® had longer mean setting time values for the US method than for the ANSI/ADA (p < .05), whilst for MTA Fillapex® no significant difference was found between the methods (p < .05). FTIR spectra demonstrated that at the setting time determined by the US method, AH Plus® and Bio‐C Sealer® were in a more advanced stage of polymerization than at the ANSI/ADA, whilst there was no significant difference for MTA Fillapex®.ConclusionsThe use of US was effective for setting time determination and measured longer values than ANSI/ADA specification for AH Plus® and Bio‐C Sealer®, identifying the entire (and not only superficial) setting of the endodontic sealers.
CIITA gene polymorphism (rs3087456) in systemic lupus erythematosus and rheumatoid arthritis: A population‐based cohort study
Authors: Lima Suelen Cristina , Gomes da Silva Isaura Isabelle Fonseca , Nascimento Denise de Queiroga , de Moura Ronald Rodrigues , Mesquita Matheus da Silva , Asano Nadja Maria Jorge , Fernandes Gisele Vagjel , Valente Lucila Maria , Rushansky Eliezer , Mariano Maria Helena Queiroz de Araújo , Xavier Ricardo Machado , Chies José Artur Bogo , Crovella Sergio , Sandrin‐Garcia Paula 
Published: June 2021

AbstractSystemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are influenced by genetic variants in immune system HLA genes. The Class II Major Histocompatibility Complex Transactivator (CIITA) is an important co‐activator of the HLA transcriptional complex; the single nucleotide variant (SNV) rs3087456 localized in the gene promoter region (−168 A/G) has been reported as able to modify its transcription level. In our study, we assessed CIITA rs3087456 SNV in 1,044 Brazilians from two Brazilian regions (Northeast and South) to verify the association with susceptibility and clinical manifestations of (SLE) and (RA) using TaqMan SNP Genotyping Assays System. We observed a protection for a recessive model (GG x AA+AG) for RA susceptibility and increased risk for erosion development in AG genotype patients. No significant association was observed for SLE susceptibility; however, we observed significant increased risk for Class IV and V nephritis development in G allele and GG genotype patients. In conclusion, we showed the contribution of CIITA rs3087456 to SLE or RA clinical features and RA susceptibility in the studied populations.
Widespread misperception about a major East Asian biogeographic boundary exposed through bibliographic survey and biogeographic meta‐analysis
Authors: Komaki Shohei 
Published: June 2021

AbstractAimThe Watase line, a major biogeographic boundary between Palearctic and Oriental realms in East Asia, is generally drawn between Akuseki and Kodakara Islands of the Northern Ryukyu archipelago, Japan. However, no evidence can be found to support the positioning of the boundary between these two tiny volcanic islands. This study aimed to confirm whether and where the biogeographical boundary should be drawn.LocationEast Asia.TaxonLand snail, ant, dragonfly, butterfly, amphibian, reptile, bird and plant.MethodsA bibliographic survey was carried out to revisit an original definition of the Watase line and its usage. Biogeographic and meta‐analyses were also performed using a Simpson dissimilarity index calculated from published distribution data to test whether and where any biogeographic boundary exists. To ensure the validity of the study design, similar surveys and analyses were conducted in another region of Southern Ryukyu, where a reliable biogeographic boundary has been proposed as a positive control.ResultsThe bibliographic survey showed that the Watase line had been described without specifying the precise position. No revised definition has been proposed for the boundary to date. Biogeographic analyses do not support the existence of a boundary between Akuseki and Kodakara Islands. Meanwhile, the presence of a boundary in Southern Ryukyu was endorsed by both the bibliographic survey and biogeographic analyses, supporting the validity of this study's design.Main conclusionsThis study revealed that the major biogeographic boundary is widely used with deviations from the original definition. Presumably, ideas based on inappropriate evidence, such as the distribution of a symbolic species and unpublished data, have been referred to without being questioned and led to the current widespread misunderstanding. Misunderstandings like these could occur at any biogeographic boundaries around the world, and thus, systematic reviews of all boundaries are needed for an appropriate understanding of biodiversity.
Identification and characterization of N6‐methyladenosine modification of circRNAs in glioblastoma
Authors: Zhang Yuhao , Geng Xiuchao , Xu Jianglong , Li Qiang , Hao Liangchao , Zeng Zhaomu , Xiao Menglin , Song Jia , Liu Fulin , Fang Chuan , Wang Hong 
Published: June 2021

AbstractThis research systematically profiled the global N6‐methyladenosine modification pattern of circular RNAs (circRNAs) in glioblastoma (GBM). Based on RNA methylation sequencing (MeRIP sequencing or N6‐methyladenosine sequencing) and RNA sequencing, we described the N6‐methyladenosine modification status and gene expression of circRNAs in GBM and normal brain tissues. N6‐methyladenosine–related circRNAs were immunoprecipitated and validated by real‐time quantitative PCR. Bioinformatics analysis and related screening were carried out. Compared with those of the NC group, the circRNAs from GBM exhibited 1370 new N6‐methyladenosine peaks and 1322 missing N6‐methyladenosine peaks. Among the loci associated with altered N6‐methyladenosine peaks, 1298 were up‐regulated and 1905 were down‐regulated. The N6‐methyladenosine level tended to be positively correlated with circRNA expression. Bioinformatics analysis was used to predict the biological function of N6‐methyladenosine–modified circRNAs and the corresponding signalling pathways. In addition, through PCR validation combined with clinical data mining, we identified five molecules of interest (BUB1, C1S, DTHD1, F13A1 and NDC80) that could be initial candidates for further study of the function and mechanism of N6‐methyladenosine–mediated GBM development. In conclusion, our findings demonstrated the N6‐methyladenosine modification pattern of circRNAs in human GBM, revealing the possible roles of N6‐methyladenosine–mediated novel noncoding RNAs in the origin and progression of GBM.