bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pilot randomized placebo‐controlled clinical trial of high‐dose gabapentin for alcohol use disorder
Authors: Mariani John J. , Pavlicova Martina , Basaraba Cale , Mamczur‐Fuller Agnieszka , Brooks Daniel J. , Bisaga Adam , Carpenter Kenneth M. , Nunes Edward V. , Levin Frances R. 
Published: June 2021

AbstractBackgroundDespite advances in the development of pharmacotherapy for alcohol use disorder (AUD), there remains a need for medications that can be administered to actively drinking outpatients to promote a reduction in harmful alcohol consumption. The primary aim of this pilot study was to determine whether high‐dose gabapentin (3600 mg/daily) is more effective than placebo in reducing harmful alcohol consumption in outpatients with AUD.MethodsForty patients (27 men) who met DSM‐IV‐TR criteria for alcohol dependence and reporting at least 4 heavy drinking days (HDD) per week were recruited at a single site. Participants were actively drinking at study entry and received double‐blind gabapentin (3600 mg/day; n = 19) or placebo (n = 20) for 8 weeks. Study medication was titrated over 5 days and administered in three divided doses (1200 mg three times per day). The proportion of HDD (primary outcome) and percent days abstinent (PDA; secondary outcome) were analyzed using generalized longitudinal mixed models with the predictors being study arm, week, study arm by week interaction, and corresponding baseline drinking measure.ResultsThere was a significant interaction between study arm and week for the proportion of HDD per week, F (7, 215) = 3.33, p = 0.002 . There was also a significant interaction between study arm and week for PDA per week, F (7, 215) = 3.11, p = 0.004. The overall retention rate was 67.5% with no significant difference in time‐to‐dropout between treatment groups. There were no serious adverse events. No participants were removed from the trial due to the development of moderate‐to‐severe alcohol withdrawal (CIWA‐Ar ≥ 13).ConclusionsGabapentin treatment rapidly titrated to a dosage of 3600 mg/day is associated with a reduction in the proportion of HDD per week and an increase in PDA per week in actively drinking outpatients with AUD. High‐dose gabapentin is potentially a feasible approach to treating AUD and deserving of further study.
Potential causal effect of posttraumatic stress disorder on alcohol use disorder and alcohol consumption in individuals of European descent: A Mendelian Randomization Study
Authors: Bountress Kaitlin E. , Wendt Frank , Bustamante Daniel , Agrawal Arpana , Webb Bradley , Gillespie Nathan , Edenberg Howard , Sheerin Christina , Johnson Emma ,   The Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group, Polimanti Renato , Amstadter Ananda 
Published: June 2021

AbstractBackgroundPosttraumatic stress disorder (PTSD) often co‐occurs with alcohol consumption (AC) and alcohol use disorder (AUD). However, it is unknown whether the same etiologic influences that underlie PTSD co‐occurring with AUD are those that underlie PTSD and AC individually.MethodsThis study used large‐scale genome‐wide association study (GWAS) data to test whether PTSD and drinks per week [DPW]/AUD are causally related to one another, and, if so, whether PTSD precedes DPW/AUD and/or vice versa. We used Mendelian Randomization methods to analyze European ancestry GWAS summary statistics from the Psychiatric Genomics Consortium (PGC; PTSD), GWAS & Sequencing Consortium of Alcohol and Nicotine Use (GSCAN; DPW), and the Million Veteran Program (MVP; AUD).ResultsPTSD exerted a potentially causal effect on AUD (β = 0.039, SE = 0.014, p = 0.005), but not on DPW (β = 0.002, SE = 0.003, p = 0.414). Additionally, neither DPW (β = 0.019, SE = 0.041, p = 0.637) nor AUD (β = 8.87 × 10−4, SE = 0.001, p = 0.441) exerted a causal effect on PTSD.ConclusionsThese findings are consistent with the self‐medication model, in which individuals misuse alcohol to cope with aversive trauma‐related symptoms. These findings extend latent analysis and molecular findings of shared and correlated risk between PTSD and alcohol phenotypes. Given the health behaviors associated with these phenotypes, these findings are important in that they suggest groups to prioritize for prevention efforts. Further, they provide a rationale for future preclinical and clinical studies examining the biological mechanisms by which PTSD may impact AUD.
World Health Organization risk drinking levels as a treatment outcome measure in topiramate trials
Authors: Hartwell Emily E. , Feinn Richard , Witkiewitz Katie , Pond Timothy , Kranzler Henry R. 
Published: June 2021

AbstractBackgroundAlthough abstinence has traditionally been considered the only suitable outcome for alcohol treatment, reduced drinking is also associated with improved functioning and medical and psychiatric outcomes. The World Health Organization (WHO) risk drinking levels (RDLs) have been shown to be valid outcome measures in treatment trials for alcohol use disorder (AUD).MethodsWe conducted a secondary analysis of two 12‐week, randomized controlled trials (RCTs), in which a total of 308 individuals with problematic alcohol use received topiramate or placebo treatment. We compared the utility of the WHO RDLs with other treatment outcomes, including self‐reported measures of alcohol consumption, alcohol‐related problems, and quality of life, and the biomarker gamma‐glutamyltransferase.ResultsTopiramate treatment was associated with small effect sizes for both a 1‐level (d = 0.26) and a 2‐level (d = 0.19) reduction in WHO RDL, effects that were not significant after correction for multiple comparisons. No heavy drinking days, one of the outcome measures recommended by the US Food and Drug Administration for alcohol medication registration trials, also exhibited a small effect (0.21), while an effect size for abstinence could not be calculated. There were medium effects of topiramate on continuous measures of percent heavy drinking days (d = 0.49) and alcohol‐related problems (d = 0.41).ConclusionsTopiramate is an efficacious pharmacotherapy for AUD. Although continuous measures of drinking and alcohol‐related problems yielded larger effect sizes than the WHO RDLs, the latter nonetheless provide a categorical alternative for use in both clinical care and pharmacotherapy trials.
The role of thrifty genes in the origin of alcoholism: A narrative review and hypothesis
Authors: Carn David , Lanaspa Miguel A. , Benner Steven A. , Andrews Peter , Dudley Robert , Andres‐Hernando Ana , Tolan Dean R. , Johnson Richard J. 
Published: June 2021

AbstractIn this narrative review, we present the hypothesis that key mutations in two genes, occurring 15 and 10 million years ago (MYA), were individually and then collectively adaptive for ancestral humans during periods of starvation, but are maladaptive in modern civilization (i.e., “thrifty genes”), with the consequence that these genes not only increase our risk today for obesity, but also for alcoholism. Both mutations occurred when ancestral apes were experiencing loss of fruit availability during periods of profound climate change or environmental upheaval. The silencing of uricase (urate oxidase) activity 15 MYA enhanced survival by increasing the ability for fructose present in dwindling fruit to be stored as fat, a consequence of enhanced uric acid production during fructose metabolism that stimulated lipogenesis and blocked fatty acid oxidation. Likewise, a mutation in class IV alcohol dehydrogenase ~10 MYA resulted in a remarkable 40‐fold increase in the capacity to oxidize ethanol (EtOH), which allowed our ancestors to ingest fallen, fermenting fruit. In turn, the EtOH ingested could activate aldose reductase that stimulates the conversion of glucose to fructose, while uric acid produced during EtOH metabolism could further enhance fructose production and metabolism. By aiding survival, these mutations would have allowed our ancestors to generate more fat, primarily from fructose, to survive changing habitats due to the Middle Miocene disruption and also during the late‐Miocene aridification of East Africa. Unfortunately, the enhanced ability to metabolize and utilize EtOH may now be acting to increase our risk for alcoholism, which may be yet another consequence of once‐adaptive thrifty genes.
The impact of mental models on the treatment and research of chronic infections due to biofilms
Authors: Bjarnsholt Thomas , Mastroianni Enrico , Kirketerp‐Møller Klaus , Stewart Philip S. , Mähr Aline Meret , Domínguez Cabañes Alonso , Nørager Rune 
Published: June 2021

Research on biofilms is predominantly made in in vitro contexts. However, in vivo observation of biofilms in human chronic infections shows distinct differences compared to in vitro biofilm growth. This could imply the use of an inadequate mental model both in research and healthcare practices. Drawing on knowledge from the cognitive sciences, we hypothesise that the predominance of in vitro research on biofilms is skewed towards a mental model promoting wrong inferences for researchers and healthcare professionals (HCPs) in the in vivo context. To explore the prevalence of such a mental model, we carried out a qualitative image analysis in which biofilm illustrations from a Google image search were coded for typical in vitro or in vivo characteristics. Further, to investigate potential misinformed and unhelpful clinical interventions related to biofilms, we conducted a quantitative questionnaire among HCPs. The questions were designed to test whether knowledge about in vitro biofilms was used in an in vivo context. This questionnaire was analysed through a chi‐squared test. Most biofilm illustrations were consistent with the in vitro model. A statistical analysis of survey responses revealed that HCPs have adequate knowledge about biofilm but often respond incorrectly when asked to apply their knowledge to in vivo contexts. The outcome of this research points to a prevalent and consolidated mental model derived from in vitro observations. This model has likely been made dominant by HCPs’ frequent exposure to visual depictions in articles and presentations. The prevalence of the in vitro model sets up the possibility of erroneous claims when the in vitro model is inadequately applied to in vivo contexts. This has potential implications for HCPs working in fields involving biofilm, such as wound care treatment.
Pertussis seroprevalence among adults of reproductive age (20–39 years) in fourteen European countries
Authors: Wehlin Lena , Ljungman Margaretha , Kühlmann‐Berenzon Sharon , Galanis Ilias , Huygen Kris , Pierard Denis , Dalby Tine , Petridou Evi , Molnár Zsuzsanna , Carollo Maria , Ausiello Clara M. , Lipnickiene Vilnele , Haider Julie , Aase Audun , Herstad Tove Karin , Rastawicki Waldemar , Rio Carla , Popovici Odette , De Ory Manchon Fernando , Bacci Sabrina , Barkoff Alex‐Mikael , Hänninen Arno , He Qiushui , Hallander Hans 
Published: June 2021

AbstractThe reported incidence of pertussis in European countries varies considerably. We aimed to study specific Bordetella pertussis seroprevalence in Europe by measuring serum IgG antibody levels to pertussis toxin (anti‐PT IgG). Fourteen national laboratories participated in this study including Belgium, Denmark, Finland, Greece, Hungary, Italy, Lithuania, Malta, Norway, Poland, Portugal, Romania, Spain, and Sweden. Each country collected approximately 250 samples (N = 7903) from the age groups 20–29 years (N = 3976) and 30–39 years (N = 3927) during 2010–2013. Samples were anonymous residual sera from diagnostic laboratories and were analyzed at the national laboratories by a Swedish reference method, a commercial ELISA kit, or were sent to Sweden for analysis. The median anti‐PT IgG concentrations ranged from 4 to 13.6 IU/mL. The proportion of samples with anti‐PT IgG ≥100 IU/mL, indicating a recent infection ranged from 0.2% (Hungary) to 5.7% (Portugal). The highest proportion of sera with anti‐PT IgG levels between 50 and <100 IU/mL, indicating an infection within the last few years, was found in Portugal (12.3%) and Italy (13.9%). This study shows that the circulation of B. pertussis is quite extensive in adults, aged 20–39 years, despite well‐established vaccination programs in Europe.
Droplet digital polymerase chain reaction assay for the detection of the minor clone of KIT D816V in paediatric acute myeloid leukaemia especially showing RUNX1‐RUNX1T1 transcripts
Authors: Sasaki Koji , Tsujimoto Shinichi , Miyake Mayuko , Uchiyama Yuri , Ikeda Junji , Yoshitomi Masahiro , Shimosato Yuko , Tokumasu Mayu , Matsuo Hidemasa , Yoshida Kenichi , Ohki Kentaro , Kaburagi Taeko , Yamato Genki , Hara Yusuke , Takeuchi Masanobu , Kinoshita Akitoshi , Tomizawa Daisuke , Taga Takashi , Adachi Souichi , Tawa Akio , Horibe Keizo , Hayashi Yasuhide , Matsumoto Naomichi , Ito Shuichi , Shiba Norio 
Published: June 2021

SummaryKIT D816V mutation within exon 17 has been particularly reported as one of the poor prognostic factors in pediatric acute myeloid leukemia (AML) with RUNX1‐RUNX1T1. The exact frequency and the prognostic impact of KIT D816V minor clones at diagnosis were not examined. In this study, the minor clones were examined and the prognostic significance of KIT D816V mutation in pediatric patients was investigated. Consequently, 24 KIT D816V mutations (7.2%) in 335 pediatric patients were identified, and 12 of 24 were only detected via the digital droplet polymerase chain reaction method. All 12 patients were confined in core binding factor (CBF)‐AML patients. The 5 year event‐free survival of the patients with KIT D816V mutation was significantly inferior to those without KIT D816V mutation (44.1% [95% confidence interval (CI), 16.0%–69.4%] vs. 74.7% [95% CI, 63.0%–83.2%] P‐value = 0.02, respectively). The 5 year overall survival was not different between the two groups (92.9% [95% CI, 59.0%–NA vs. 89.7% [95% CI, 69.6%–96.8%] P‐value = 0.607, respectively). In this study, KIT D816V minor clones in patients with CBF‐AML were confirmed and KIT D816V was considered as a risk factor for relapse in patients with RUNX1‐RUNX1T1‐positive AML.
Plant–herbivore assemblages composed of endophagous and exophagous insects have different patterns of diversity and specialization in Brazilian savannas
Authors: de Araújo Walter S. , Oliveira Jefferson B. B. S. 
Published: June 2021

AbstractPlant–insect interactions can differ between endophagous and exophagous insect guilds, and this can influence the response patterns of these guilds to anthropogenic changes in natural habitats. We compared the species richness, abundance, and species‐level specialization of plant–herbivore assemblages composed of distinct insect guilds in Neotropical savannas. Assemblages of chewing insects were the richest in species, and the gallers were the most abundant. Galling species were more specialized than other guilds, and sucking insects were more specialized than chewers. Our results show that insect guilds are similarly influenced by disturbance, which decreased species richness and increased specialization of insect species.
Animal‐mediated seed dispersal in India: Implications for conservation of India’s biodiversity
Authors: Sengupta Asmita 
Published: June 2021

AbstractEffective seed dispersal is critical for forest regeneration and recruitment as well as the restoration of degraded lands. Most tropical tree species depend on frugivorous animals to disperse their seeds; frugivore‐mediated seed dispersal is thus crucial for biodiversity conservation in megadiverse tropical systems such as India. The fauna in India are increasingly threatened due to anthropogenic interventions such as deforestation and hunting. Thus, it is imperative to have an understanding of plant–frugivore interactions across the country to curb further biodiversity loss by ensuring the maintenance of these ecological processes. In this paper, I reviewed the literature on seed dispersal by animals in India to identify important groups that disperse many plant species and/or are the only recorded dispersers of certain plant species. Hornbills, bulbuls, bears, cattle, deer, civets, elephants, macaques, nilgais, Old World fruit bats, and wild pigs meet these criteria; overall 18 species were included in this list. Six of these species are currently “Threatened” on the IUCN Red List and their loss can lead to limited dispersal for at least 86 plant species. I suggest ensuring the protection of the important seed dispersers identified in this paper, irrespective of their conservation status, to prevent further biodiversity loss. The review reveals that plant–animal interactions in India are understudied and a major knowledge gap exists with regard to seed dispersal networks within the country.
Landscape genetic analysis suggests stronger effects of past than current landscape structure on genetic patterns of Primula veris
Authors: Reinula Iris , Träger Sabrina , Hernández‐Agramonte Ignacio M. , Helm Aveliina , Aavik Tsipe 
Published: June 2021

AbstractAimRecent changes in land use have led to substantial loss and fragmentation of semi‐natural grasslands. We assessed the relative effect of current and historical landscape composition, and landscape change on the genetic diversity and gene flow of a characteristic grassland plant.LocationCalcareous grasslands on Muhu and Saaremaa islands in Western Estonia, Europe.MethodsWe used landscape genetic methods to study the genetic patterns of the grassland plant Primula veris. We applied a high‐throughput sequencing method (double‐digest restriction site‐associated DNA sequencing, ddRADseq) to obtain 2,619 putatively neutral single‐nucleotide polymorphism (SNP) markers. We examined the impact of the historical (80 years ago) and current amount and edge density of 19 grasslands, the amount of woody elements in the surroundings of the study grasslands and the change in the area of these habitats on the current genetic diversity within populations and genetic differentiation between populations of P. veris.ResultsGenetic diversity within populations of P. veris was lower in landscapes with more pronounced grassland loss over the past 80 years. Higher historical grassland edge density in the surrounding landscape led to higher genetic diversity of P. veris. Higher historical proportion of grasslands between the study populations led to lower genetic differentiation, indicating higher (historical) gene flow between those populations.Main conclusionsAlthough the study grasslands experienced a drastic loss in the area and connectivity over the past century, patterns of genetic diversity and gene flow of P. veris still largely mirror the effect of historical landscape, especially grassland edge density and at larger scales the historical proportion of grasslands between study populations. Thus, measures of genetic diversity and gene flow in P. veris may have a lagged response to landscape change, offering a window for preserving the still existing genetic diversity through immediate restoration activities.
The impact of antiplatelet and antithrombotic regimen after TAVI
Authors: Mach Markus , Watzal Victoria , Cuhaj Carina , Hasan Waseem , Poschner Thomas , Szalkiewicz Philipp , Strouhal Andreas , Adlbrecht Christopher , Delle‐Karth Georg , Grabenwöger Martin , Winkler Bernhard 
Published: June 2021

AbstractBackgroundWe compared the outcomes and adverse events of TAVI patients based on the discharge and long‐term antiplatelet or anticoagulant treatment regimens (single antiplatelet [SAPT] vs. dual antiplatelet [DAPT] vs. anticoagulation [OAC] vs. no treatment [NT]).MethodsThe outcome of 532 consecutive patients treated with TAVI was evaluated. As the main study endpoint, the 1‐year all‐cause mortality was chosen to compare the different discharge treatment regimens and the 3‐year all‐cause mortality to compare the different long‐term treatment regimens. The secondary endpoints were adverse events as defined by the Valve Academic Research Consortium‐II.ResultsOne‐year survival after TAVI was highest amongst patients treated with DAPT compared to SAPT (P < .001) and OAC (P = .003), and patients under OAC demonstrated improved 1‐year survival over patients treated with SAPT (P = .006). Furthermore, there was a strong trend towards improved 3‐year survival for patients in the OAC cohort treated with non–vitamin K antagonists compared to vitamin K antagonists (N‐VKAs vs. VKA; log‐rank P = .056).ConclusionThe lower all‐cause mortality for DAPT within the first year and N‐VKAs over VKA within the first 3 years warrant considerable attention in further recommendations of antithrombotic and anticoagulation regimens after TAVI.
Fit mothers for a healthy future
Authors: Stevanović‐Silva Jelena , Beleza Jorge , Coxito Pedro , Costa Rui Carlos , Ascensão António , Magalhães José 
Published: June 2021

AbstractSpecial issue‘FOIEGRAS—Bioenergetic Remodelling in the Pathophysiology and Treatment of Non‐Alcoholic Fatty Liver Disease’.BackgroundNon‐alcoholic fatty liver disease (NAFLD) emerges as significant health burden worldwide. Lifestyle changes, unhealthy dietary habits and physical inactivity, can trigger NAFLD development. Persisting on these habits during pregnancy affects in utero environment and prompts a specific metabolic response in foetus resulting in offspring metabolic maladjustments potentially critical for developing NAFLD later in life. The increasing prevalence of NAFLD, particularly in children, has shifted the research focus towards preventive and therapeutic strategies. Yet, designing effective approaches that can break the NAFLD intergenerational cycle becomes even more complicated. Regular physical exercise (PE) is a powerful non‐pharmacological strategy known to counteract deleterious metabolic outcomes. In this narrative review, we aimed to briefly describe NAFLD pathogenesis focusing on maternal nutritional challenge and foetal programming, and to provide potential mechanisms behind the putative intergenerational effect of PE against metabolic diseases, including liver diseases.MethodsFollowing detailed electronic database search, recent existing evidence about NAFLD development, intergenerational programming and gestational exercise effects was critically analysed and discussed.ResultsPE during pregnancy could have a great potential to counteract intergenerational transmission of metabolic burden. The interplay between different PE roles—metabolic, endocrine and epigenetic—could offer a more stable in utero environment to the foetus, thus rescuing offspring vulnerability to metabolic disturbances.ConclusionsThe better understanding of maternal PE beneficial consequences on offspring metabolism could reinforce the importance of PE during pregnancy as an indispensable strategy in improving offspring health.