bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurobiological substrates of the dread of future losses
Authors: Wang Pinchun , Zhang Han , Deng Kun , Chen Shuning , Im Hohjin , Zhu Wenwei , Yang Shaofeng , Wei Shiyu , Wang He , Wang Qiang 
Published: November 2022

Abstract
When anticipating future losses, people respond by exhibiting 1 of 2 starkly distinct behavioral decision patterns: the dread of future losses (DFL) and the preference of future losses (vs. immediate losses). Yet, how to accurately discriminate between those who exhibit dread vs. preference and uncover the potential neurobiological substrates underlying these 2 groups remain understudied. To address this, we designed a novel experimental task in which the DFL group was defined as selecting immediate-loss options &gt;50% in the trials with approximate subjective value in immediate and delayed options (n = 16), otherwise coding as the preference of future losses (PFL). At the behavioral level, DFL exhibited higher weight for delayed losses than immediate losses via the logistic regression model. At the neural level, DFL manifested hypoactivations on subjective valuations of delayed losses, atypical brain pattern when choosing immediate-loss options, and decreased functional coupling between the valuation and choice-systems when making decisions related to immediate-loss alternatives compared with PFL. Moreover, both these brain activations subserving distinct decision processes and their interactions predicted individual decisions and behavioral preferences. Furthermore, morphological analysis also revealed decreased right precuneus volume in DFL compared with PFL, and brain activations related to valuation and choice process mediated the associations between this region volume and behavioral performances. Taken together, these findings help to clarify potential cognitive and neural mechanisms underlying the DFL and provide a clear discrimination strategy.
Efficacy and Tolerability of Concomitant Use of Bedaquiline and Delamanid for Multidrug- and Extensively Drug-Resistant Tuberculosis: A Systematic Review and Meta-Analysis
Authors: Holmgaard Freja Breth , Guglielmetti Lorenzo , Lillebaek Troels , Andersen Åse Bengaard , Wejse Christian , Dahl Victor Naestholt 
Published: November 2022

AbstractThe introduction of two novel drugs, bedaquiline and delamanid, has given hope for better and shorter treatments of drug-resistant tuberculosis. A systematic review was conducted to evaluate the efficacy and safety of concomitant bedaquiline and delamanid administration. Pooled estimates of World Health Organization–defined favorable treatment outcome and significant QTc-interval prolongation (QTc ≥500 ms or ≥60 ms increase from baseline) were calculated using a random-effects model. Thirteen studies including a total of 1031 individuals with multidrug-resistant/rifampicin-resistant tuberculosis who received bedaquiline and delamanid were included. The pooled estimate of favorable treatment outcome was 73.1% (95% confidence interval [CI]: 64.3–81.8%). Sputum culture conversion at 6 months ranged from 61% to 95%. Overall, the pooled proportion of QTc-prolongation was 7.8% (95% CI: 4.1–11.6%) and few cardiac events were reported (0.8%; n = 6/798). Rates of sputum culture conversion and favorable treatment outcome were high in patients treated concomitantly with bedaquiline and delamanid, and the treatment seemed tolerable with low rates of clinically significant cardiac toxicity.
Bezlotoxumab Therapy for Recurrent Clostridium difficile Infection in an Ulcerative Colitis Patient
Authors: Fein Aaron , Kern Cody , Barrett Terrance , Perry Courtney 
Published: November 2022

Abstract

Background
Clostridium difficile infection (CDI) is the most common infectious cause of nosocomial diarrhea, comprising 10%–20% of all cases. CDI is a significant complication in patients with inflammatory bowel disease (IBD). New monoclonal antibody therapies have emerged as leading treatment options for recurrent CDI (rCDI). Bezlotoxumab, a novel monoclonal antibody, has shown success in decreasing the recurrence rates of patients with rCDI. However, data extrapolating diminished rCDI in patients with concomitant IBD is limited.

Methods
A single infusion of bezlotoxumab @ 10mg/kg was given with fidaxomicin 200mg for 10 days in a patient with rCDI and ulcerative colitis

Results
The patient’s symptoms improved, inflammatory markers normalized, and she has remained asymptomatic for twelve months

Conclusions
This case supports the findings in the MODIFY I/II trials that Bezlotoxumab is a viable treatment option of rCDI in IBD patients.
Effect of inclisiran on lipids in primary prevention: the ORION-11 trial
Authors: Ray Kausik K , Kallend David , Leiter Lawrence A , Raal Frederick J , Koenig Wolfgang , Jaros Mark J , Schwartz Gregory G , Landmesser Ulf , Garcia Conde Lorena , Wright R Scott ,   ORION-11 Investigators
Published: November 2022

Abstract

Aims
Patients often require combination therapies to achieve LDL cholesterol (LDL-C) targets for the primary prevention of atherosclerotic cardiovascular disease. This study investigates the effect of inclisiran, a small interfering ribonucleic acid targeting hepatic proprotein convertase subtilisin/kexin type 9 production, in primary prevention patients with elevated LDL-C despite statins.

Methods and results
This pre-specified analysis of the placebo-controlled, randomized ORION-11 trial included 203 individuals at risk of, but without prior, cardiovascular events and LDL-C ≥2.6 mmol/L, despite maximally tolerated statins. Inclisiran 284 mg or placebo was administered on Days 1, 90, and thereafter every 6 months up to 540 days. Co-primary endpoints were percentage LDL-C change from baseline to Day 510 and time-adjusted change from baseline after Day 90 and up to Day 540. Key secondary endpoints included percentage and absolute changes in atherogenic lipoproteins. Safety was assessed over 540 days. The mean baseline (SD) LDL-C was 3.6 (1.5) mmol/L. At Day 510, the placebo-corrected LDL-C change with inclisiran was −43.7% [95% confidence interval (CI): −52.8 to −34.6] with a corresponding time-adjusted change of −41.0% (95% CI: −47.8 to −34.2); (P &lt; 0.0001). The placebo-corrected absolute change in LDL-C at Day 510 with inclisiran was −1.5 mmol/L (95% CI: −1.8 to −1.2), with a respective time-adjusted change of −1.3 mmol/L (95% CI: −1.6 to −1.1). Inclisiran significantly lowered non-HDL cholesterol and apolipoprotein B (apoB) at Day 510 vs. placebo (P &lt; 0.0001 for both), with a greater likelihood of attaining lipoprotein and apoB goals, and was well-tolerated except for mainly mild, treatment-emergent adverse events at the injection site.

Conclusion
Inclisiran was generally well-tolerated in primary prevention patients with elevated LDL-C, who derived significant reductions in atherogenic lipoprotein levels with twice-yearly maintenance dosing.
Accuracy and precision of frequency–size distribution scaling parameters as a function of dynamic range of observations: example of the Gutenberg–Richter law b-value for earthquakes
Authors: Geffers G-M , Main I G , Naylor M 
Published: November 2022

SUMMARY
Many natural hazards exhibit inverse power-law scaling of frequency and event size, or an exponential scaling of event magnitude (m) on a logarithmic scale, for example the Gutenberg–Richter law for earthquakes, with probability density function p(m) ∼ 10−bm. We derive an analytic expression for the bias that arises in the maximum likelihood estimate of b as a function of the dynamic range r. The theory predicts the observed evolution of the modal value of mean magnitude in multiple random samples of synthetic catalogues at different r, including the bias to high b at low r and the observed trend to an asymptotic limit with no bias. The situation is more complicated for a single sample in real catalogues due to their heterogeneity, magnitude uncertainty and the true b-value being unknown. The results explain why the likelihood of large events and the associated hazard is often underestimated in small catalogues with low dynamic range, for example in some studies of volcanic and induced seismicity.
Estimates of excess mortality for the five Nordic countries during the COVID-19 pandemic 2020−2021
Authors: Kepp Kasper P , Björk Jonas , Kontis Vasilis , Parks Robbie M , Bæk Kristoffer T , Emilsson Louise , Lallukka Tea 
Published: November 2022

AbstractBackgroundExcess mortality during the COVID-19 pandemic is of major scientific and political interest.MethodsWe critically reviewed different estimates of all-cause excess mortality for the five Nordic countries (Denmark, Finland, Iceland, Norway and Sweden), which have been much studied during the COVID-19 pandemic, using the latest register data to discuss uncertainties and implications.ResultsWe show using back-calculation of expected deaths from Nordic all-cause deaths that the Institute for Health Metrics and Evaluation model is a clear outlier in the compared estimates and likely substantially overestimates excess mortality of Finland and Denmark, and probably Sweden. Our review suggests a range of total Nordic excess deaths of perhaps 15 000–20 000, but results are sensitive to assumptions in the models as shown.ConclusionsWe document substantial heterogeneity and uncertainty in estimates of excess mortality. All estimates should be taken with caution in their interpretation as they miss detailed account of demographics, such as changes in the age group populations over the study period.
Ketanserin Reverses the Acute Response to LSD in a Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Participants
Authors: Becker Anna M , Klaiber Aaron , Holze Friederike , Istampoulouoglou Ioanna , Duthaler Urs , Varghese Nimmy , Eckert Anne , Liechti Matthias E 
Published: November 2022

Abstract

Background
Lysergic acid diethylamide (LSD) is currently being investigated in psychedelic-assisted therapy. LSD has a long duration of acute action of 8–11 hours. It produces its acute psychedelic effects via stimulation of the serotonin 5-hydroxytryptamine-2A (HT2A) receptor. Administration of the 5-HT2A antagonist ketanserin before LSD almost fully blocks the acute subjective response to LSD. However, unclear is whether ketanserin can also reverse the effects of LSD when administered after LSD.

Methods
We used a double-blind, randomized, placebo-controlled, crossover design in 24 healthy participants who underwent two 14-hour sessions and received ketanserin (40 mg p.o.) or placebo 1 hour after LSD (100 µg p.o.). Outcome measures included subjective effects, autonomic effects, acute adverse effects, plasma brain-derived neurotrophic factor levels, and pharmacokinetics up to 12 hours.

Results
Ketanserin reversed the acute response to LSD, thereby significantly reducing the duration of subjective effects from 8.5 hours with placebo to 3.5 hours. Ketanserin also reversed LSD-induced alterations of mind, including visual and acoustic alterations and ego dissolution. Ketanserin reduced adverse cardiovascular effects and mydriasis that were associated with LSD but had no effects on elevations of brain-derived neurotrophic factor levels. Ketanserin did not alter the pharmacokinetics of LSD.

Conclusions
These findings are consistent with an interaction between ketanserin and LSD and the view that LSD produces its psychedelic effects only when occupying 5-HT2A receptors. Ketanserin can effectively be used as a planned or rescue option to shorten and attenuate the LSD experience in humans in research and LSD-assisted therapy.

Trial registry
ClinicalTrials.gov (NCT04558294)
Intranasal M2SR (M2-Deficient Single Replication) H3N2 Influenza Vaccine Provides Enhanced Mucosal and Serum Antibodies in Adults
Authors: Eiden Joseph , Fierro Carlos , Schwartz Howard , Adams Mark , Ellis Kimberly J , Aitchison Roger , Herber Renee , Hatta Yasuko , Marshall David , Moser Michael J , Belshe Robert , Greenberg Harry , Coelingh Kathleen , Kawaoka Yoshihiro , Neumann Gabriele , Bilsel Pamuk 
Published: November 2022

Abstract

Background
We previously demonstrated that an intranasal dose of 108 50% tissue culture infectious dose (TCID50) M2-deficient single replication (M2SR) influenza vaccine protected against highly drifted H3N2 influenza challenge in a subset of subjects who demonstrated ≥2-fold increase in microneutralization (MN) antibodies to Belgium2015 (the challenge strain) after vaccination. Here, we describe a phase 1b, observer-blinded, dose-escalation study demonstrating an increased proportion of responders with this signal of immune protection.

Methods
Serosusceptible subjects aged 18–49 years were randomized to receive 2 doses (108–109 TCID50) of M2SR or placebo administered 28 days apart. Clinical specimens were collected before and after each dose. The primary objective was to demonstrate safety of M2SR vaccines.

Results
The vaccine was well tolerated at all dose levels. Against Belgium2015, ≥ 2-fold increases in MN antibodies were noted among 40% (95% confidence interval [CI], 24.9%–56.7%) of subjects following a single 108 TCID50 M2SR dose and among 80.6% (95% CI, 61.4%–92.3%) after 109 dose (P &lt; .001). A single 109 TCID50 dose of M2SR generated ≥4-fold hemagglutination inhibition antibody seroconversion against the vaccine strain in 71% (95% CI, 52.0%–85.8%) of recipients. Mucosal and cellular immune responses were also induced.

Conclusions
These results indicate that M2SR may provide substantial protection against infection with highly drifted strains of H3N2 influenza.

Clinical Trials Registration
NCT03999554.
High concordance in plasma and CSF HIV-1 drug resistance mutations despite high cases of CSF viral escape in individuals with HIV-associated cryptococcal meningitis in Botswana
Authors: Kelentse Nametso , Moyo Sikhulile , Choga Wonderful T , Lechiile Kwana , Leeme Tshepo B , Lawrence David S , Kasvosve Ishmael , Musonda Rosemary , Mosepele Mosepele , Harrison Thomas S , Jarvis Joseph N , Gaseitsiwe Simani 
Published: November 2022

Abstract

Objectives
We compared the patterns of HIV-1 drug resistance mutations between the CSF and plasma of individuals with HIV-associated cryptococcal meningitis.

Methods
This is a cross-sectional study of archived CSF and plasma samples collected from ART-exposed participants recruited in the Phase 3 AmBisome Therapy Induction Optimisation randomized controlled trial (ISRCTN72509687) conducted in Botswana between 2018 and 2021. HIV-1 RT and protease genes were genotyped using next-generation sequencing and HIV-1 drug resistance mutations were compared between the CSF and plasma compartments stratified by thresholds of ≥20% and &lt;20%.

Results
Overall, 66.7% (16/24) of participants had at least one HIV-1 drug resistance mutation in the CSF and/or plasma. A total of 15/22 (68.2%) participants had HIV-1 drug resistance mutations at ≥20% threshold in the plasma and of those, 11 (73.3%) had been on ART longer than 6 months. HIV-1 drug resistance mutations were highly concordant between the CSF and plasma at ≥20% threshold despite a substantial number of individuals experiencing CSF viral escape and with only 54.5% with CSF WBC count ≥20 cells/mm3. Minority HIV-1 drug resistance mutations were detected in 20.8% (5/24) of participants. There were no mutations in the CSF that were not detected in the plasma.

Conclusions
There was high concordance in HIV-1 drug resistance mutations in the CSF and plasma, suggesting intercompartmental mixing and possibly a lack of compartmentalization. Some individuals harboured minority HIV-1 drug resistance mutations, demonstrating the need to employ more sensitive genotyping methods such as next-generation sequencing for the detection of low-abundance mutations.
Pivmecillinam, the paradigm of an antibiotic with low resistance rates in Escherichia coli urine isolates despite high consumption
Authors: Frimodt-Møller Niels , Simonsen Gunnar Skov , Larsen Anders Rhod , Kahlmeter Gunnar 
Published: November 2022

Abstract

Objectives
Pivmecillinam, the oral version of mecillinam, represents one of the major recommended and used antibiotics for empiric and targeted treatment of urinary tract infections in primary care in Denmark, Norway and Sweden. Mecillinam resistant mutants in Escherichia coli develop easily in vitro, but their fitness cost has been shown to be high.

Methods
We revisited the resistance and consumption data from the monitoring programmes in the three countries and compared pivmecillinam with ciprofloxacin from 2010 to 2020.

Results
Mecillinam resistance rates in Escherichia coli remained around 6% in Denmark and Norway relative to a constant consumption in Norway of 1.6–1.8 DID (defined daily doses per 1000 inhabitants per day), and even increasing in Denmark from 1.6 to 2.3 DID. In Sweden resistance was significantly lower at 4% related to the lower consumption of 0.5 DID. For ciprofloxacin, resistance rates fluctuated around 6%–12%, highest in Sweden with the highest consumption (0.8–0.6 DID) and lowest in Denmark (0.55–0.35 DID) and Norway (0.7–0.3 DID), although consumption declined significantly in all three countries.

Conclusions
Pivmecillinam is an example of an antibiotic, which easily develops resistance in vitro, but apparently can be used broadly in primary care without increase in resistance rates.
Alfalfa Weevil (Coleoptera: Curculionidae) Resistance to Lambda-cyhalothrin in the Western United States
Authors: Rodbell E A , Hendrick M L , Grettenberger I M , Wanner K W 
Published: November 2022

Abstract
Forage alfalfa (Medicago sativa L. [Fabales: Fabaceae]) is a key agricultural commodity of the western region of the United States. The key insect pest of alfalfa, Hypera postica Gyllenhal (Coleoptera: Curculionidae), has developed resistance to the most common class of insecticide used to manage its damage. Alfalfa weevil samples from 71 commercial alfalfa fields located in Arizona, California, Montana, Oregon, Washington, and Wyoming were assayed for susceptibility to lambda-cyhalothrin during 2020–2022 using a laboratory concentration-response assay. Seventeen field sites representing all six states were highly resistant to lambda-cyhalothrin (resistance ratios &gt; 79.6) and bioassay mortality often did not exceed 50% even at the highest concentration tested (3.30 µg/cm2 in 2020 and 10.00 µg/cm2 in 2021–2022). Field sites assayed with more than one pyrethroid active ingredient indicated likely cross-resistance between lambda-cyhalothrin and zeta-cypermethrin (type II pyrethroids) and variable and/or limited potential cross-resistance to permethrin (type I pyrethroid). Thirty-two field sites representing five states were susceptible to lambda-cyhalothrin (resistance ratios ranging from 1 to 20). While resistance is widespread, integrated resistance management strategies including rotating mode of action groups, applying chemical control tactics only when economic thresholds have been met, and utilizing cultural control tactics can be employed to slow the further development of resistance.
Host Range and Phenology of Sugarcane Aphid (Hemiptera: Aphididae) and Natural Enemy Community in Sorghum in Haiti
Authors: Exilien Romain , Brodeur Jacques , Fournier Valérie , Martini Xavier 
Published: November 2022

Abstract
To determine the factors leading to outbreaks of the sugarcane aphid, Melanaphis sacchari, (Zehntner) (Hemiptera: Aphididae) in sorghum in Haiti, a survey was carried out on farms during two cropping seasons, spring and fall of 2018. A total of 45 plots in three Haitian regions were monitored from the five-leaf stage to grain ripening. Infestation with M. sacchari was significantly higher in spring than in fall, except in one location. Melanaphis sacchari populations varied significantly according to phenological stages of sorghum, with significantly higher abundance during the heading and flowering stages than other stages. In and around sorghum fields, the sugarcane aphid was observed on plants from three families: Poaceae, Malvaceae, and Cucurbitaceae. Aphid natural enemies found in sorghum fields consisted of eight species of ladybeetles (Coleoptera: Coccinellidae), one hoverfly (Diptera: Syrphidae), one lacewing (Neuroptera: Chrysopidae), and one predatory midge (Diptera: Cecidomyiidae). In addition to these predators, two parasitoid species, Adialytus sp. (Hymenoptera: Braconidae) and Pachyneuron aphidis (Bouché) (Hymenoptera: Pteromalidae), emerged from sugarcane aphid mummies. Predator and parasitoid densities were highly affected by growing season, with most of the biological control happening in fall. This study provides insights on sugarcane aphid management in Haiti and the Caribbean Islands.
Population structure and genetic variation of fragmented mountain birch forests in Iceland
Authors: Pálsson Snæbjörn , Wasowicz Pawel , Heiðmarsson Starri , Magnússon Kristinn Pétur 
Published: November 2022

AbstractBetula pubescens Ehrh. (mountain birch) is the only forest-forming tree in Iceland. Since human settlement (874 AD), the continuous 25,000 to 30,000 km2 forest has shrunk to 1.200 km2 of fragmented patches, making it a good object to study population genetic consequences of habitat fragmentation and disturbance. Further, genetic studies have also shown that hybridization between the tetraploid (2n = 56) B. pubescens and the diploid (2n = 28) Betula nana L. (dwarf birch) occurs among Iceland’s natural populations. This study assessed the genetic variation within and among 11 birch forests remaining across Iceland. Genotype-by-sequencing methodology provided a total of 24,585 single nucleotide polymorphisms (SNP´s), with a minor allele frequency &gt;5% for genetic analyses. The analysis showed similar diversity within forests, suggesting that fragmentation and hybridization have had a limited effect on the genetic variation within sites. A clear genetic divergence is found among forests from the different regions of Iceland that may reflect historical isolation; the differentiation between forests increased with geographic distances reflecting isolation by distance. Information on the distribution of genetic variation of birch in Iceland is essential for its conservation and to establish genotype–phenotype associations to predict responses to new environmental conditions imposed by climate change and novel biotic/abiotic stressors.
Life History Metrics for Culex tarsalis (Diptera: Culicidae) and Culicoides sonorensis (Diptera: Ceratopogonidae) Are Not Impacted by Artificial Feeding on Defibrinated Versus EDTA-treated Blood
Authors: Swanson Dustin A , McGregor Bethany L 
Published: November 2022

Abstract
Artificial blood feeding is a common practice for the study and maintenance of blood-feeding arthropod colonies. Commercially purchased blood is often treated to prevent clot-formation using either mechanical or chemical means. For many hematophagous insects, the effect that different anticoagulation methods may have on life history metrics is unclear. In the current study, Culex tarsalis Coquillett and Culicoides sonorensis Wirth & Jones were fed blood treated with either mechanical (defibrination) or chemical (K2 EDTA) anticoagulation methods. Several blood feeding and life history metrics were evaluated between treatment groups including proportion blood feeding, fecundity, fertility, and mortality. No significant differences were found for any of the measured life history metrics for either species. For experiments measuring aspects of these blood feeding and life history traits, blood treated using either defibrination or K2 EDTA anticoagulants should not impact experimental outcomes.