bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wolbachia in scale insects: a distinct pattern of infection frequencies and potential transfer routes via ant associates
Authors: Sanaei Ehsan , Lin Yen‐Po , Cook Lyn G. , Engelstädter Jan 
Published: November 2021

SummaryWolbachia is one of the most successful endosymbiotic bacteria of arthropods. Known as the ‘master of manipulation’, Wolbachia can induce a wide range of phenotypes in its host that can have far‐reaching ecological and evolutionary consequences and may be exploited for disease and pest control. However, our knowledge of Wolbachia's distribution and the infection rate is unevenly distributed across arthropod groups such as scale insects. We fitted a distribution of within‐species prevalence of Wolbachia to our data and compared it to distributions fitted to an up‐to‐date dataset compiled from surveys across all arthropods. The estimated distribution parameters indicate a Wolbachia infection frequency of 43.6% (at a 10% prevalence threshold) in scale insects. Prevalence of Wolbachia in scale insects follows a distribution similar to exponential decline (most species are predicted to have low prevalence infections), in contrast to the U‐shaped distribution estimated for other taxa (most species have a very low or very high prevalence). We observed no significant associations between Wolbachia infection and scale insect traits. Finally, we screened for Wolbachia in scale insect's ecological associates. We found a positive correlation between Wolbachia infection in scale insects and their ant associates, pointing to a possible route of horizontal transfer of Wolbachia.
Reduction of the resistome risk from cow slurry and manure microbiomes to soil and vegetable microbiomes
Authors: Jauregi Leire , Epelde Lur , González Aitor , Lavín José Luis , Garbisu Carlos 
Published: November 2021

SummaryIn cow farms, the interaction between animal and environmental microbiomes creates hotspots for antibiotic resistance dissemination. A shotgun metagenomic approach was used to survey the resistome risk in five dairy cow farms. To this purpose, 10 environmental compartments were sampled: 3 of them linked to productive cows (fresh slurry, stored slurry, slurry‐amended pasture soil); 6 of them to non‐productive heifers and dry cows (faeces, fresh manure, aged manure, aged manure‐amended orchard soil, vegetables‐lettuces and grazed soil); and, finally, unamended control soil. The resistome risk was assessed using MetaCompare, a computational pipeline which scores the resistome risk according to possible links between antibiotic resistance genes (ARGs), mobile genetic elements (MGEs) and human pathogens. The resistome risk decreased from slurry and manure microbiomes to soil and vegetable microbiomes. In total (sum of all the compartments), 18,157 ARGs were detected: 24% related to ansamycins, 21% to multidrugs, 14% to aminoglycosides, 12% to tetracyclines, 9% to β‐lactams, and 9% to macrolide–lincosamide–streptogramin B. All but two of the MGE‐associated ARGs were only found in the animal dejections (not in soil or vegetable samples). Several ARGs with potential as resistome risk markers (based on their presence in hubs of co‐occurrence networks and high dissemination potential) were identified. As a precautionary principle, improved management of livestock dejections is necessary to minimize the risk of antibiotic resistance.
Salivary free light chains and salivary immunoglobulins as potential non‐invasive biomarkers in primary Sjögren's syndrome
Authors: Sandhya Pulukool , Kabeerdoss Jayakanthan , Christudoss Pamela , Arulraj Roy , Mandal Santosh Kumar , Janardana Ramya , Chebbi Pramod Prahlad , Ganesan Maya Pavalasseril , Mahasampath Gowri , Danda Debashish 
Published: November 2021

AbstractBackgroundB cells contribute significantly to the pathogenesis of primary Sjögren's syndrome (pSS). Free light chains (FLCs) are generated during the production of immunoglobulins (Igs) and are surrogates of B cell activity. We hypothesized that salivary FLCs and salivary Igs could represent salivary gland inflammation and therefore, serve as biomarkers in pSS.MethodsPatients >18 years old fulfilling the American College of Rheumatology / European League Against Rheumatism (EULAR) 2016 criteria for pSS and age‐matched healthy and disease controls (sicca non‐pSS, rheumatoid arthritis, systemic lupus erythematosus) were recruited for this cross‐sectional study. FLCs in saliva and serum were measured by immunoturbidimetry. Serum and salivary Igs were measured by nephelometry and enzyme‐linked immunosorbent assay, respectively. Area under the receiver operator characteristic curve was determined. The factors influencing the serum and salivary FLCs in pSS were determined using backward linear regression.ResultsA total of 78 patients with pSS, 76 healthy controls and 62 disease controls were recruited. Median EULAR SS disease activity index (interquartile range) was 1 (3.75). Serum FLCκ and FLCλ, salivary FLCλ, serum and salivary IgG, salivary IgM was significantly higher in the pSS group compared to the controls. Areas under the curve for salivary FLCλ, serum FLCκ, serum and salivary IgG were 0.75, 0.72, 0.78 and 0.77, respectively. Regression analysis showed that salivary FLCκ, salivary FLCλ and salivary IgG were associated with positive salivary gland histopathology. Use of immunosuppressants and glucocorticoids was associated with lower values of salivary parameters.ConclusionSalivary FLCλ and salivary IgG were significantly different between pSS and control groups and could be potential non‐invasive biomarkers in pSS. These findings should be confirmed in larger longitudinal studies.
Does sex alter the relationship between CYP2B6 variation, hydroxybupropion concentration and bupropion‐aided smoking cessation in African Americans? A moderated mediation analysis
Authors: Chenoweth Meghan J. , Peng Annie R. , Zhu Andy Z. X. , Cox Lisa Sanderson , Nollen Nikki L. , Ahluwalia Jasjit S. , Benowitz Neal L. , Knight Jo , Swardfager Walter , Tyndale Rachel F. 
Published: November 2021

AbstractBackground and AimsCYP2B6, a genetically variable enzyme, converts bupropion to its active metabolite hydroxybupropion. CYP2B6 activity and bupropion‐aided cessation differ between women and men. The aim of this study was to determine whether genetically normal (versus reduced) CYP2B6 activity increases bupropion‐aided cessation in African American smokers via higher hydroxybupropion concentration, and whether this differs by sex.Design and SettingSecondary analysis of a smoking cessation clinical trial (NCT00666978).Participants/CasesAfrican American light smokers (≤ 10 cigarettes/day).InterventionsParticipants were treated with bupropion for 7 weeks.MeasurementsParticipants with detectable bupropion and/or hydroxybupropion concentrations were divided into normal (n = 64) and reduced (n = 109) CYP2B6 activity groups based on the presence of decreased‐function CYP2B6*6 and CYP2B6*18 alleles. Biochemically verified smoking cessation was assessed at week 3, end of treatment (7 weeks) and follow‐up (26 weeks).FindingsNormal (versus reduced) CYP2B6 activity was associated with increased cessation at week 7, which was mediated by higher hydroxybupropion concentration [odds ratio (OR) = 1.25, 95% confidence interval (CI) = 1.03, 1.78]; this mediation effect persisted at week 26 (OR = 1.23, 95% CI = 1.02, 1.70). The mediation effect was similar in women (n = 116; OR = 1.33, 95% CI = 1.01, 2.30) and men (n = 57; OR = 1.33, 95% CI = 0.92, 3.87). Moreover, sex did not appear to moderate the mediation effect, although this should be tested in a larger sample.ConclusionsIn African American light smokers with verified early bupropion use, genetically normal CYP2B6 activity appears to be indirectly associated with greater smoking cessation success in a relationship mediated by higher hydroxybupropion concentration. The mediating effect of higher hydroxybupropion concentration on smoking cessation persists beyond the active treatment phase and does not appear to differ by sex.
Prenatal smoking, alcohol and caffeine exposure and maternal‐reported attention deficit hyperactivity disorder symptoms in childhood: triangulation of evidence using negative control and polygenic risk score analyses
Authors: Haan Elis , Sallis Hannah M. , Zuccolo Luisa , Labrecque Jeremy , Ystrom Eivind , Reichborn‐Kjennerud Ted , Andreassen Ole , Havdahl Alexandra , Munafò Marcus R. 
Published: November 2021

AbstractBackground and aimsStudies have indicated that maternal prenatal substance use may be associated with offspring attention deficit hyperactivity disorder (ADHD) via intrauterine effects. We measured associations between prenatal smoking, alcohol and caffeine consumption with childhood ADHD symptoms accounting for shared familial factors.DesignFirst, we used a negative control design comparing maternal and paternal substance use. Three models were used for negative control analyses: unadjusted (without confounders), adjusted (including confounders) and mutually adjusted (including confounders and partner's substance use). The results were meta‐analysed across the cohorts. Secondly, we used polygenic risk scores (PRS) as proxies for exposures. Maternal PRS for smoking, alcohol and coffee consumption were regressed against ADHD symptoms. We triangulated the results across the two approaches to infer causality.SettingWe used data from three longitudinal pregnancy cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC) in the United Kingdom, Generation R study (GenR) in the Netherlands and Norwegian Mother, Father and Child Cohort study (MoBa) in Norway.ParticipantsPhenotype data available for children were: NALSPAC = 5455–7751; NGENR = 1537–3119; NMOBA = 28 053–42 206. Genotype data available for mothers was: NALSPAC = 7074; NMOBA = 14 583.MeasurementsA measure of offspring ADHD symptoms at age 7–8 years was derived by dichotomizing scores from questionnaires and parental self‐reported prenatal substance use was measured at the second pregnancy trimester.FindingsThe pooled estimate for maternal prenatal substance use showed an association with total ADHD symptoms [odds ratio (OR)SMOKING = 1.11, 95% confidence interval (CI) = 1.00–1.23; ORALCOHOL = 1.27, 95% CI = 1.08–1.49; ORCAFFEINE = 1.05, 95% CI = 1.00–1.11], while not for fathers (ORSMOKING = 1.03, 95% CI = 0.95–1.13; ORALCOHOL = 0.83, 95% CI = 0.47–1.48; ORCAFFEINE = 1.02, 95% CI = 0.97–1.07). However, maternal associations did not persist in sensitivity analyses (substance use before pregnancy, adjustment for maternal ADHD symptoms in MoBa). The PRS analyses were inconclusive for an association in ALSPAC or MoBa.ConclusionsThere appears to be no causal intrauterine effect of maternal prenatal substance use on offspring attention deficit hyperactivity disorder symptoms.
Transitioning to a high volume centre for Whipple pancreaticoduodenectomy in Western Australia: a single centre experience
Authors: Yau Ho‐Cing Victor , Lester Leanne , Johansson Mikael 
Published: November 2021

AbstractBackgroundPancreaticoduodenectomy (PD) is a curative resection for peri‐ampullary tumours associated with high rates of peri‐operative mortality and morbidity. The global trend is towards the establishment of high volume centres to reduce this. Australia faces geographical and population distribution challenges. Western Australia has centralized PD to two centres and we present the results of our institution in transitioning to a high volume centre.MethodsThis was a prospective database of all PDs performed at our institution from 1 January 2005 to 2 April 2020. Mortality outcomes included peri‐operative, 30 day and 90 day mortality. Complications, readmission and reinterventions at 90 days were recorded. The annual volume exceeded 20 from 2015. Outcomes prior to this were compared to characterize the transition to a high volume centre.ResultsOne hundred and twenty eight PDs were performed in Period 1 (1 January 2005–31 December 2014) and 170 in the high volume Period 2 (1 January 2015–2 April 2020). There was a non‐statistically significant reduction in 90 day mortality in Period 2 (4.69% versus 1.18%, p = 0.06). There was a reduction in clinically significant post‐operative pancreatic fistulas (31.25% versus 11.76%, p < 0.05), delayed gastric emptying (39.84% versus 22.35%, p < 0.05) and transfusion requirements (56.25% versus 17.65%, p < 0.05). Severe complications (Clavien–Dindo III or greater) were reduced (30.47% versus 18.24%, p < 0.05).ConclusionSince establishing a high volume service, there was a reduction in post‐operative complications and 90 day mortality. This is in line with outcomes from international centres and demonstrates the improvements that can be made.
Dexamethasone‐mediated inhibition of Notch signalling blocks the interaction of leukaemia and mesenchymal stromal cells
Authors: Ahmed Helal Mohammed Mohammed , Nimmagadda Subbaiah Chary , Al‐Matary Yahya S. , Fiori Maren , May Tobias , Frank Daria , Patnana Pradeep Kumar , Récher Christian , Schliemann Christoph , Mikesch Jan‐Henrik , Koenig Thorsten , Rosenbauer Frank , Hartmann Wolfgang , Tuckermann Jan , Dührsen Ulrich , Lanying Wei , Dugas Martin , Opalka Bertram , Lenz Georg , Khandanpour Cyrus 
Published: November 2021

SummaryAcute myeloid leukaemia (AML) is a haematological malignancy characterized by a poor prognosis. Bone marrow mesenchymal stromal cells (BM MSCs) support leukaemic cells in preventing chemotherapy‐induced apoptosis. This encouraged us to investigate leukaemia‐BM niche‐associated signalling and to identify signalling cascades supporting the interaction of leukaemic cells and BM MSC. Our study demonstrated functional differences between MSCs originating from leukaemic (AML MSCs) and healthy donors (HD MSCs). The direct interaction of leukaemic and AML MSCs was indispensable in influencing AML cell proliferation. We further identified an important role for Notch expression and its activation in AML MSCs contributing to the enhanced proliferation of AML cells. Supporting this observation, overexpression of the intracellular Notch domain (Notch ICN) in AML MSCs enhanced AML cells’ proliferation. From a therapeutic point of view, dexamethasone treatment impeded Notch signalling in AML MSCs resulting in reduced AML cell proliferation. Concurrent with our data, Notch inhibitors had only a marginal effect on leukaemic cells alone but strongly influenced Notch signalling in AML MSCs and abrogated their cytoprotective function on AML cells. In vivo, dexamethasone treatment impeded Notch signalling in AML MSCs leading to a reduced number of AML MSCs and improved survival of leukaemic mice. In summary, targeting the interaction of leukaemic cells and AML MSCs using dexamethasone or Notch inhibitors might further improve treatment outcomes in AML patients.
Drought‐induced reductions in plant defenses: Insights from extrafloral nectaries in the Caatinga dry forest
Authors: Câmara Talita , Reis Daniela Queiroz de Assis , Arnan Xavier , de Oliveira Fernanda Maria Pereira , de Arruda Emília Cristina Pereira , Leal Inara Roberta 
Published: November 2021

AbstractExtrafloral nectaries (EFNs) are anti‐herbivory defense‐related glands. We measured morphological and anatomical EFN traits in Pityrocarpa moniliformis trees along a rainfall gradient in Caatinga dry forest. We observed a reduction in structural EFN traits as rainfall decreased. We conclude that this reduction is a cost‐saving strategy, probably mediated by ants.
Physicochemical properties determining drug detection in skin
Authors: Bittremieux Wout , Advani Rohit S. , Jarmusch Alan K. , Aguirre Shaden , Lu Aileen , Dorrestein Pieter C. , Tsunoda Shirley M. 
Published: November 2021

AbstractChemicals, including some systemically administered xenobiotics and their biotransformations, can be detected noninvasively using skin swabs and untargeted metabolomics analysis. We sought to understand the principal drivers that determine whether a drug taken orally or systemically is likely to be observed on the epidermis by using a random forest classifier to predict which drugs would be detected on the skin. A variety of molecular descriptors describing calculated properties of drugs, such as measures of volume, electronegativity, bond energy, and electrotopology, were used to train the classifier. The mean area under the receiver operating characteristic curve was 0.71 for predicting drug detection on the epidermis, and the SHapley Additive exPlanations (SHAP) model interpretation technique was used to determine the most relevant molecular descriptors. Based on the analysis of 2561 US Food and Drug Administration (FDA)‐approved drugs, we predict that therapeutic drug classes, such as nervous system drugs, are more likely to be detected on the skin. Detecting drugs and other chemicals noninvasively on the skin using untargeted metabolomics could be a useful clinical advancement in therapeutic drug monitoring, adherence, and health status.
Co‐existence of BRAF V600E‐mutated malignant melanoma and BRAF V600E‐mutated Langerhans cell histiocytosis: A case report
Authors: Goto Keisuke , Yoshikawa Shusuke , Kiyohara Yoshio , Kukita Yoji , Miura Keiko , Oishi Takuma 
Published: November 2021

AbstractLangerhans cell histiocytosis (LCH) is a neoplastic condition of Langerhans cells, and can be associated with other neoplasms, especially BRAF‐mutant hematological tumors and papillary thyroid carcinoma. Here we present the first case of co‐existing LCH and low cumulative sun damage (low‐CSD) melanoma, both of which had a BRAF V600E mutation. A 49‐year‐old man had a 45 × 43 × 15 mm semi‐pedunculated, pigmented tumor in his back but had no other systemic symptoms. Histopathology revealed a 2‐mm‐sized incidental focus of LCH within a large lesion of low‐CSD melanoma. Diffuse immunoexpression of CD1a, langerin/CD207, S100 protein, and BRAF (VE1) was observed in the focus of LCH. Sanger sequencing with microdissection confirmed BRAF V600E mutation in the component of LCH. Interestingly, the advanced melanoma also harbored the same BRAF V600E mutation, although the significance of this tumor combination is still unknown.
Analytics for multiperiod risk‐averse newsvendor under nonstationary demands
Authors: Yu Yugang , Wang Ting , Shi Ye 
Published: November 2021

AbstractBased on the practice of a Chinese food manufacturer, this article develops a predictive and prescriptive analytics research on a multiperiod risk‐averse newsvendor problem with nonstationary demands. We start with a predictive analysis that aims to transform the nonstationary demand series into a predictable stationary one, and then develop inventory models for deriving prescriptive decisions based on transformed stationary series. When transforming the nonstationary demand series, we consider three commonly used methods—detrending (DET), differencing (DIT), and percentage change transformations (PCT)—which all effectively convert nonstationary demand series into stationary ones. These methods not only have desired simplicity and interpretability but also provide better predictive performance than the autoregressive integrated moving (ARIMA) process. Moreover, we develop an ensemble of the three transformation methods following the model averaging approach, which provides comparable predictions as the machine learning approaches. When developing prescriptive inventory decisions, we construct dynamic risk‐averse newsvendor models for the three methods having different structures, and find that the optimal order quantities under DET and DIT monotonically change as the newsvendor becomes more risk‐averse, but the optimal order quantity under PCT may not. Similarly, we also develop a heuristic ensemble of the inventory decisions under the three methods, which can lead to better profit performance. An extensive numerical simulation based on the manufacturer's historical data set shows that the heuristic ensemble inventory decision outperforms the sole decision generated by every transformation method and achieves an average performance improvement up to 92.25%. Several extensions are also considered to confirm the robustness of our findings.
Early intervention in psychosis in emerging countries: Findings from a first‐episode psychosis programme in the Ribeirão Preto catchment area, southeastern Brazil
Authors: Corrêa‐Oliveira Gabriel Elias , Scarabelot Luis Felipe , Araújo Jéssica Morais , Boin André Campiolo , de Paula Pessoa Rebeca Mendes , Leal Livio Rodrigues , Del‐Ben Cristina Marta 
Published: November 2021

AbstractAimPeople presenting with first‐episode psychosis (FEP) can benefit from early intervention programmes. However, such programmes are scarce in low‐ and middle‐income countries (LMICs). In Brazil, there are a few programmes, but they are unequally distributed across the country. We aimed to describe the implementation and performance of the Ribeirão Preto Early Intervention in Psychosis Programme (Ribeirão Preto‐EIP), an outpatient service for patients presenting with FEP residing in the Ribeirão Preto catchment area in Southeastern Brazil.MethodsA detailed description of the service, staff and theoretical framework was compiled. Furthermore, a retrospective cohort study of patients attending the programme throughout 4 years (2015–2018) was conducted. Data were obtained by analysing the medical records of all patients, and sociodemographic and diagnostic stability information for this period was recorded.ResultsThe Ribeirão Preto‐EIP had 358 new referrals during the study period. Among them, 237 patients were assessed for an average (median) duration of 14 months. Most patients were male (64.1%) and single (84.8%). The median age was 23.5 years (range, 9–86 years). Schizophrenia was the main diagnosis (43.4%), followed by substance‐induced (25.7%) and affective (18.6%) psychosis. Referrals occurred from emergency, inpatient, community‐based mental health and primary care services.ConclusionsProgrammes such as the Ribeirão Preto‐EIP demonstrate that early intervention in psychosis is feasible in LMICs despite significant challenges for their access and integration in the health system. Strategic scale‐up policies could be undertaken to offer better short‐ and long‐term outcomes for individuals presenting with FEP and their families.
Distinct sensory‐ and goal‐related signals underlie the gap effect in the superior colliculus
Authors: Marino Robert A. , Levy Ron , Munoz Douglas P. 
Published: November 2021

AbstractThe removal of a fixation point (FP) prior to the appearance of a saccade target (gap effect) influences pre‐motor circuits and reduces saccadic reaction time (SRT). Saccade preparation signals underlying the gap effect have been observed within the intermediate layers of the superior colliculus (SCi). Neurons in the caudal SCi, coding a target location, increase their activity during the gap, while neurons in the rostral SCi, with tonic activity related to visual fixation, decrease activity. However, the gap effect confounds two factors: (1) a goal‐driven temporal warning component (upcoming saccade target appearance) and (2) a stimulus‐driven sensory component (FP disappearance). These factors combine to reduce SRT and elicit pre‐target responses in the SCi. To dissociate warning and sensory effects, we altered the luminance of the FP during the gap period (renamed warning period) such that it could increase, decrease, or stay the same. Faster SRTs resulted with larger decrements in FP luminance. Different categories of SCi warning period activity were evaluated: (1) always increasing or decreasing or (2) sensory‐linked responses to changes in FP luminance. In the caudal SCi (at the location coding the target), all activity correlated negatively with SRT (i.e., saccade facilitation), and two categories of activity were observed (always increasing or opposing FP luminance changes). In the rostral SCi, four categories of activity were observed: activity that increased or followed the change in FP luminance correlated positively with SRT (i.e., saccade inhibition), while activity that decreased or opposed FP luminance changes correlated negatively with SRT. Such SCi activity reflected both goal‐driven saccade preparation signals and FP sensory properties.