Miracle-dz/UniFAR-FTUs huggingface dataset:
Why are retractions so difficult

Retractions of published work from journals have moved from being a rather arcane topic of debate for those obsessed with publication ethics to having their own blog (http://retractionwatch.com/) and increasing media attention. However, as Retraction Watch clearly shows, journals’ policies and practices are far from uniform and there is evidence that not all seriously flawed work is retracted. The Committee on Publication Ethics (COPE) developed retraction guidelines in 2009 [1], and guidance is also available from other organizations such as the Council of Science Editors [2], yet, despite these guidelines, retractions continue to be regarded as problematic by editors and publishers. This essay addresses some of the difficulties associated with retractions.
Early progression after BR is associated with high risk of transformation in advanced stage follicular lymphoma.

Despite widespread use of bendamustine and rituximab (BR) as frontline therapy for advanced stage follicular lymphoma (FL), little is known about the risk of early progression or incidence of histological transformation. We performed a retrospective analysis of a population-based cohort of 296 patients with advanced stage FL treated with frontline BR and maintenance rituximab. As previously demonstrated, outcomes with this regimen are excellent, with 2-year EFS estimated at 85% [95% CI 80-89%] and 2-year OS 92% (95% CI 88-95%). Progression of disease within 24 months (POD24) occurred in 13% of patients and was associated with a significantly inferior outcome with 2-year OS of 38% (95% CI 20-55%). The only significant risk factor for POD24 at baseline was elevated LDH (p<0.001). Importantly, the majority of POD24 patients (76%) had transformed disease. Compared to a historical cohort treated with RCVP, EFS has improved and the risk of POD24 has decreased, but a higher proportion of patients with POD24 harbor transformation. The overall incidence of transformation appears unchanged. The presence of occult or early transformation is the main driver of POD24 in FL patients treated with frontline BR. Identification of biomarkers and improved management strategies for transformation will be crucial to improving outcomes.
Assessing predictions of the impact of variants on splicing in CAGI5

Precision medicine and sequence‐based clinical diagnostics seek to predict disease risk or to identify causative variants from sequencing data. The Critical Assessment of Genome Interpretation (CAGI) is a community experiment consisting of genotype‐phenotype prediction challenges; participants build models, undergo assessment, and share key findings. In the past, few CAGI challenges have addressed the impact of sequence variants on splicing. In CAGI5, two challenges (Vex‐seq and MaPSY) involved prediction of the effect of variants, primarily single‐nucleotide changes, on splicing. Although there are significant differences between these two challenges, both involved prediction of results from high‐throughput exon inclusion assays. Here, we discuss the methods used to predict the impact of these variants on splicing, their performance, strengths, and weaknesses, and prospects for predicting the impact of sequence variation on splicing and disease phenotypes.
Pulmonary effects of inhaled cannabis smoke

ABSTRACT Background: The smoke generated from cannabis delivers biologically active cannabinoids and a number of combustion-derived toxins, both of which raise questions regarding the impact of cannabis smoking on lung function, airway inflammation and smoking-related lung disease. Objectives: Review the potential effects of cannabis smoking on respiratory symptoms, lung function, histologic/molecular alterations in the bronchial mucosa, smoking-related changes in alveolar macrophage function and the potential clinical impact of cannabis smoking on chronic obstructive pulmonary disease, lung cancer and pulmonary infections. Methods: Focused literature review. Results: The carcinogens and respiratory toxins in cannabis and tobacco smoke are similar but the smoking topography for cannabis results in higher per-puff exposures to inhaled tar and gases. The frequency of chronic cough, sputum and wheeze and the presence of airway mucosal inflammation, goblet cell and vascular hyperplasia, metaplasia and cellular disorganization are similar between cannabis smokers and tobacco smokers. Cannabis smoke has modest airway bronchodilator properties but of unclear clinical significance. While clear evidence exists for progression to obstructive lung disease and emphysema in chronic tobacco smokers, the effects from habitual cannabis use are less clear. Evidence suggests that alveolar macrophages from cannabis smokers have deficits in cytokine production and antimicrobial activity not present in cells from tobacco smokers. Conclusions: Solid conclusions regarding the respiratory consequences of regular cannabis smoking are difficult to make due to a relative paucity of literature, confounding by concurrent tobacco smoking and reports of conflicting outcomes. Additional well-controlled clinical studies on the pulmonary consequences of habitual cannabis use are needed.
Facultative and anaerobic consortia of haloalkaliphilic ureolytic micro‐organisms capable of precipitating calcium carbonate

Development of biomineralization technologies has largely focused on microbially induced carbonate precipitation (MICP) via Sporosarcina pasteurii ureolysis; however, as an obligate aerobe, the general utility of this organism is limited. Here, facultative and anaerobic haloalkaliphiles capable of ureolysis were enriched, identified and then compared to S. pasteurii regarding biomineralization activities.
A Fast Algorithm for the Simplified Theory of Rolling Contact

SUMMARY An algorithm “Fastsim” for the simplified theory of rolling contact is described which is 15-25 times as fast as the existing programs Simrol (Kalker), and 3 times as fast as Rolcon (Knothe). The relative total force computed with Fastsim differs at most 0.2 from that calculated with Simrol, Simcona (Goree & Law), Rolcon, and the “exact” program Duvorol (Kalker). Descriptions and lists of an Algol 60, and HP 67 program version are available upon request: the Fortran IV version is given in the paper.
IBD prevalence in Lothian, Scotland, derived by capture–recapture methodology

Objective IBD prevalence is estimated to be rising, but no detailed, recent UK data are available. The last reported prevalence estimate in the UK was 0.40% in 2003. We aimed to establish the current, and project future, prevalence in Lothian, Scotland. Design We conducted an all-age multiparameter search strategy using inpatient IBD international classification of disease (ICD-10) coding (K50/51)(1997–2018), IBD pathology coding (1990–2018), primary and secondary care prescribing data (2009–2018) and a paediatric registry, (1997–2018) to identify ‘possible’ IBD cases up to 31/08/2018. Diagnoses were manually confirmed through electronic health record review as per Lennard-Jones/Porto criteria. Autoregressive integrated moving average (ARIMA) regression was applied to forecast prevalence to 01/08/2028. Results In total, 24 601 possible IBD cases were identified of which 10 499 were true positives. The point prevalence for IBD in Lothian on 31/08/2018 was 784/100 000 (UC 432/100 000, Crohn’s disease 284/100 000 and IBD unclassified (IBDU) 68/100 000). Capture–recapture methods identified an additional 427 ‘missed’ cases (95% CI 383 to 477) resulting in a ‘true’ prevalence of 832/100 000 (95% CI 827 to 837). Prevalence increased by 4.3% per year between 2008 and 2018 (95% CI +3.7 to +4.9%, p<0.0001). ARIMA modelling projected a point prevalence on 01/08/2028 of 1.02% (95% CI 0.97% to 1.07%) that will affect an estimated 1.53% (95% CI 1.37% to 1.69%) of those >80 years of age. Conclusions We report a rigorously validated IBD cohort with all-age point prevalence on 31/08/2018 of 1 in 125, one of the highest worldwide.
Influence of Climate on Google Internet Searches for Pruritus Across 16 German Cities: Retrospective Analysis

Background The burden of pruritus is high, especially among patients with dermatologic diseases. Identifying trends in pruritus burden and people’s medical needs is challenging, since not all affected people consult a physician. Objective The purpose of this study was to investigate pruritus search behavior trends in Germany and identify associations with weather factors. Methods Google AdWords Keyword Planner was used to quantify pruritus-related search queries in 16 German cities from August 2014 to July 2018. All identified keywords were qualitatively categorized and pruritus-related terms were descriptively analyzed. The number of search queries per 100,000 inhabitants of each city was compared to environmental factors such as temperature, humidity, particulate matter 10 micrometers or less in diameter (PM10), and sunshine duration to investigate potential correlations. Results We included 1150 pruritus-related keywords, which resulted in 2,851,290 queries. “Pruritus” (n=115,680) and “anal pruritus” (n=102,390) were the most-searched-for keywords. Nearly half of all queries were related to the category localization, with Berlin and Munich having a comparatively high proportion of people that searched for pruritus in the genital and anal areas. People searched more frequently for information on chronic compared to acute pruritus. The most populated cities had the lowest number of queries per 100,000 inhabitants (Berlin, n=13,641; Hamburg, n=18,303; and Munich, n=21,363), while smaller cities (Kiel, n=35,027; and Freiburg, n=39,501) had the highest. Temperature had a greater effect on search query number (beta -7.94, 95% CI -10.74 to -5.15) than did PM10 (beta -5.13, 95% CI -7.04 to -3.22), humidity (beta 4.73, 95% CI 2.70 to 6.75), or sunshine duration (beta 0.66, 95% CI 0.36 to 0.97). The highest relative number of search queries occurred during the winter (ie, December to February). Conclusions By taking into account the study results, Google data analysis helps to examine people’s search frequency, behavior, and interest across cities and regions. The results indicated a general increase in search queries during the winter as well as differences across cities located in the same region; for example, there was a decline in search volume in Saarbrucken, while there were increases in Cologne, Frankfurt, and Dortmund. In addition, the detected correlation between search volume and weather data seems to be valuable in predicting an increase in pruritus burden, since a significant association with rising humidity and sunshine duration, as well as declining temperature and PM10, was found. Accordingly, this is an unconventional and inexpensive method to identify search behavior trends and respective inhabitants’ needs.
Triiodothyronine Reduces Vascular Dysfunction Associated with Hypertension by Attenuating Protein Kinase G/Vasodilator-Stimulated Phosphoprotein Signaling

Vascular dysfunction associated with hypertension comprises hypercontractility and impaired vasodilation. We have previously demonstrated that triiodothyronine (T3), the active form of thyroid hormone, has vasodilatory effects acting through rapid onset mechanisms. In the present study, we examined whether T3 mitigates vascular dysfunction associated with hypertension. To test the direct effects of T3 in hypertensive vessels, aortas from female Dahl salt-sensitive (Dahl SS) rats fed a high-salt diet (8% NaCl, HS group) and their age-matched controls fed a standard low-salt diet (0.3% NaCl, LS group) for 16 weeks were isolated and used in ex vivo vascular reactivity studies. We confirmed that the HS group exhibited a higher systolic blood pressure in comparison with the control LS group and displayed aortic remodeling. Aortas from both groups were pretreated with T3 (0.1 μM) for 30 minutes at 37°C in a 5% CO2 incubator before functional vascular studies. T3 treatment significantly attenuated hypercontractility and improved impaired endothelium-dependent vasodilation in aortas from the HS group. These vascular improvements in response to T3 were accompanied by increased phosphorylation of vasodilator-stimulated phosphoprotein (VASP) at serine 239, a vasodilatory factor of the cGMP-dependent protein kinase (PKG)/VASP signaling pathway in vascular smooth muscle cells. Moreover, increased production of reactive oxygen species in aortas from the HS group were significantly reduced by T3, suggesting a potential antioxidant effect of T3 in the vasculature. These results demonstrate that T3 can mitigate hypertension-related vascular dysfunction through the VASP signaling pathway and by reducing vascular ROS production. SIGNIFICANCE STATEMENT This study demonstrates that triiodothyronine (T3) directly acts on vascular tone and has a beneficial effect in hypertension-induced vascular dysfunction. T3 augmented vasodilation and diminished vasoconstriction in blood vessels from hypertensive rats in association with activation of the protein kinase G/vasodilator-stimulated phosphoprotein signaling pathway that activates vascular relaxation and exerted an antioxidant effect. Collectively, these results show that T3 is a potential vasoprotective agent with rapid action on hypertension-related vascular dysfunction.
Fluoxetine‐induced plasticity in the visual cortex outlasts the duration of the naturally occurring critical period

Heightened neuronal plasticity expressed during early postnatal life has been thought to permanently decline once critical periods have ended. For example, monocular deprivation is able to shift ocular dominance in the mouse visual cortex during the first months of life, but this effect is lost later in life. However, various treatments, such as the antidepressant fluoxetine, can reactivate a critical period‐like plasticity in the adult brain. When monocular deprivation is supplemented with chronic fluoxetine administration, a major shift in ocular dominance is produced after the critical period has ended. In the current study, we characterized the temporal patterns of fluoxetine‐induced plasticity in the adult mouse visual cortex, using in vivo optical imaging. We found that artificially induced plasticity in ocular dominance extended beyond the duration of the naturally occurring critical period and continued as long as fluoxetine was administered. However, this fluoxetine‐induced plasticity period ended as soon as the drug was not given. These features of antidepressant‐induced plasticity may be useful when designing treatment strategies involving long‐term antidepressant treatment in humans.
Assessment of ERBB2 and TOP2α gene status and expression profile in feline mammary tumors: findings and guidelines

In humans, the ERBB2 gene amplification and overexpression are biomarkers for invasive breast cancer and a therapeutic target. Also, TOP2α gene aberrations predict the response to anthracycline-based adjuvant chemotherapy. Although feline mammary tumors (FMTs) are good models in comparative oncology, scarce data is available regarding the ERBB2 and TOP2α status. In this study, and for the first time, the ERBB2 DNA status and RNA levels of intracellular (ICD) and extracellular (ECD) coding regions were compared with TOP2α gene status and expression profile, in samples of FMTs and disease-free tissues from the same animal. Results showed that ERBB2 and TOP2α gene status are highly correlated (r=0.87, p<0.0001, n=25), with few tumor samples presenting amplification. Also, the majority of the FMTs showed ERBB2 overexpression coupled with TOP2α overexpression (r=0.87, p<0.0001, n=27), being the ERBB2-ICD and ECD transcripts highly correlated (r=0.97, p<0.0001, n=27). Significant associations were found between TOP2α gene status or ERBB2 and TOP2α RNA levels with several clinicopathological parameters. This work highlights the need of experimental designs for a precise evaluation of ERBB2 and TOP2α gene status and its expression in FMTs, to improve their clinical management and to further validate them as a suitable model for comparative oncology studies.
PACAP27 induces migraine-like attacks in migraine patients

Introduction Pituitary adenylate cyclase-activating polypeptide (PACAP) is found in two functional isoforms, namely PACAP38 and PACAP27. The migraine-inducing properties of PACAP38 are well studied. However, it is not known whether the lesser-known and under-studied protein isoform, PACAP27, can also induce migraine attacks. Here, we studied the effect of human PACAP27 infusion on induction of migraine in a provocation model. Methods In a crossover study, 20 migraine without aura patients were randomly assigned to receive human PACAP27 (10 picomol/kg/min) or saline (placebo) infusion over 20 min. We recorded the migraine and associated symptoms. Results All patients completed the study. PACAP27 provoked migraine-like attacks in 11 patients (55%) and two developed attacks after placebo (10%) (p = 0.022). The headache intensity and duration after PACAP27 was significantly greater compared to placebo (p = 0.003). Conclusion PACAP27 triggers migraine attacks without aura. These novel data strengthen the role of PACAP and its receptors in migraine pathogenesis.
Transcriptional regulation of homeostatic and disease‐associated‐microglial genes by IRF1, LXRβ, and CEBPα

Microglia transform from homeostatic to disease‐associated‐microglia (DAM) profiles in neurodegeneration. Within DAM, we recently identified distinct pro‐inflammatory and anti‐inflammatory sub‐profiles although transcriptional regulators of homeostatic and distinct DAM profiles remain unclear. Informed by these studies, we nominated CEBPα, IRF1, and LXRβ as likely regulators of homeostatic, pro‐inflammatory and anti‐inflammatory DAM states and performed in‐vitro siRNA studies in primary microglia to identify roles of each transcriptional factor (TF) in regulating microglial activation, using an integrated transcriptomics, bioinformatics and experimental validation approach. Efficient (>70%) silencing of TFs in microglia revealed reciprocal regulation between each TF specifically following pro‐inflammatory activation. Neuroinflammatory transcriptomic profiling of microglia coupled with qPCR validation revealed distinct gene clusters with unique patterns of regulation by each TF, which were independent of LPS stimulation. While all three TFs (especially IRF1 and LXRβ) positively regulated core DAM genes (Apoe, Axl, Clec7a, Tyrobp, and Trem2) as well as homeostatic and pro‐inflammatory DAM genes, LPS, and IFNγ increased pro‐inflammatory DAM but suppressed homeostatic and anti‐inflammatory DAM gene expression via an Erk1/2‐dependent signaling pathway. IRF1 and LXRβ silencing suppressed microglial phagocytic activity for polystyrene microspheres as well as fAβ42 while IRF1 silencing strongly suppressed production of pro‐inflammatory cytokines in response to LPS. Our studies reveal complex transcriptional regulation of homeostatic and DAM profiles whereby IRF1, LXRβ, and CEBPα positively regulate both pro‐ and anti‐inflammatory DAM genes while activating stimuli independently augment pro‐inflammatory DAM responses and suppress homeostatic and anti‐inflammatory responses via Erk signaling. This framework can guide development of therapeutic immuno‐modulatory strategies for neurodegeneration.
ChIP-exo analysis highlights Fkh1 and Fkh2 transcription factors as hubs that integrate multi-scale networks in budding yeast

Abstract The understanding of the multi-scale nature of molecular networks represents a major challenge. For example, regulation of a timely cell cycle must be coordinated with growth, during which changes in metabolism occur, and integrate information from the extracellular environment, e.g. signal transduction. Forkhead transcription factors are evolutionarily conserved among eukaryotes, and coordinate a timely cell cycle progression in budding yeast. Specifically, Fkh1 and Fkh2 are expressed during a lengthy window of the cell cycle, thus are potentially able to function as hubs in the multi-scale cellular environment that interlocks various biochemical networks. Here we report on a novel ChIP-exo dataset for Fkh1 and Fkh2 in both logarithmic and stationary phases, which is analyzed by novel and existing software tools. Our analysis confirms known Forkhead targets from available ChIP-chip studies and highlights novel ones involved in the cell cycle, metabolism and signal transduction. Target genes are analyzed with respect to their function, temporal expression during the cell cycle, correlation with Fkh1 and Fkh2 as well as signaling and metabolic pathways they occur in. Furthermore, differences in targets between Fkh1 and Fkh2 are presented. Our work highlights Forkhead transcription factors as hubs that integrate multi-scale networks to achieve proper timing of cell division in budding yeast.
Activation of Nrf2 signaling by sitagliptin and quercetin combination against β‐amyloid induced Alzheimer's disease in rats

The objective of this study was to evaluate the neuroprotective effect of sitagliptin (Sita), quercetin (QCR) and its combination in β‐amyloid (Aβ) induced Alzheimer's disease (AD). Male Sprague–Dawley rats, weighing between 220 and 280 g were used for experiment. Rats were divided into 5 groups (n = 10) and the groups were as follows: (a) Sham control; (b) Aβ injected; (c) Aβ injected + Sita 100; (d) Aβ injected + QCR 100; and (e) Aβ injected + Sita 100 + QCR 100. Cognitive performance was observed by the Morris water maze (MWM), biochemical markers, for example, MDA, SOD, CAT, GSH, Aβ1‐42 level, Nrf2/HO‐1 expression and histopathological study of rat brain were estimated. Pretreatment with Sita, QCR and their combination showed a significant increase in escape latency in particular MWM cognitive model. Further co‐administration of sita and QCR significantly reduced Aβ1‐42 level when compared with individual treatment. Biochemical markers, for example, increased SOD, CAT and GSH, decreased MDA were seen, and histopathological studies revealed the reversal of neuronal damage in the treatment group. Additionally, Nrf2/HO‐1 pathway in rat's brain was significantly increased by Sita, QCR and their combination. Pretreatment with QCR potentiates the action of Sita in Aβ induced AD in rats. The improved cognitive memory could be because of the synergistic effect of the drugs by decreasing Aβ1‐42 level, antioxidant activity and increased expression of Nrf2/HO‐1 in rat brain.
Observation of sea breeze interactions at and near Hong Kong International Airport

Hong Kong International Airport (HKIA) is located in a coastal environment and is occasionally affected by sea breezes. High air temperatures relative to sea surface temperature, coupled with light winds or moderate east to northeasterly winds are favourable conditions for the development of a sea breeze at the airport. In the afternoon of 27 April 2000, sea breezes affected the airport and a sea breeze front was formed by convergence between the westerly sea breeze and strengthening easterlies. An aircraft landing at HKIA encountered the sea breeze front and reported wind shear with airspeed gain of up to 15 kt at a height of 30 m (100 feet) above ground. Surface wind observations and Doppler velocity data of a Terminal Doppler Weather Radar (TDWR) allow quantitative analysis of the wind shear event. Shortly after the wind shear event, the TDWR also captured interesting interactions between the sea breeze front and an area of passing showers. This paper presents a quantitative analysis of the wind shear event and observations of the sea breeze interactions by the TDWR. Copyright © 2003 Royal Meteorological Society