A Graph-Based Approach for Mitigating Multi-Sided Exposure Bias in Recommender Systems

Fairness is a critical system-level objective in recommender systems that has been the subject of extensive recent research. A specific form of fairness is supplier exposure fairness, where the objective is to ensure equitable coverage of items across all suppliers in recommendations provided to users. This is especially important in multistakeholder recommendation scenarios where it may be important to optimize utilities not just for the end user but also for other stakeholders such as item sellers or producers who desire a fair representation of their items. This type of supplier fairness is sometimes accomplished by attempting to increase aggregate diversity to mitigate popularity bias and to improve the coverage of long-tail items in recommendations. In this article, we introduce FairMatch, a general graph-based algorithm that works as a post-processing approach after recommendation generation to improve exposure fairness for items and suppliers. The algorithm iteratively adds high-quality items that have low visibility or items from suppliers with low exposure to the users’ final recommendation lists. A comprehensive set of experiments on two datasets and comparison with state-of-the-art baselines show that FairMatch, although it significantly improves exposure fairness and aggregate diversity, maintains an acceptable level of relevance of the recommendations.

Does Perceived Advertising Value Alleviate Advertising Avoidance in Mobile Social Media? Exploring Its Moderated Mediation Effects

It is known that perceived intrusiveness and privacy concerns, mediated by irritation, indirectly affect advertising avoidance. This research attempts to verify the importance of perceived advertising value by investigating its moderated mediation effect on the links between those endogenous variables. The research model was empirically verified with data derived from 374 valid off-line responses. Analysis found that both perceived intrusiveness and privacy concerns increased irritation in using mobile social media. Irritation caused by perceived intrusiveness and privacy concerns had positive mediating effects on advertising avoidance. Ubiquity increased perceived intrusiveness and privacy concerns, whereas personalization reduced perceived intrusiveness. Customization increased perceived intrusiveness, whereas informativeness significantly reduced it. Social interaction increased privacy concerns, whereas social integration decreased them. The moderated mediation effect of perceived advertising value among women was negative. In the low-exposure group, a negative moderated mediation effect of perceived advertising value on the relationship between irritation and advertising avoidance was also found.

Hematopoiesis and innate immunity: an inseparable couple for good and bad times, bound together by an hormetic relationship

Hematopoietic and immune cells originate from a common hematopoietic/lymphopoietic stem cell what explains that these different cell types often share the same receptors and respond to similar factors. Moreover, the common goal of both lineages is to ensure tissue homeostasis under steady-state conditions, fight invading pathogens, and promote tissue repair. We will highlight accumulating evidence that innate and adaptive immunity modulate several aspects of hematopoiesis within the hormetic zone in which the biological response to low exposure to potential stressors generally is favorable and benefits hematopoietic stem/progenitor cells (HSPCs). Innate immunity impact on hematopoiesis is pleiotropic and involves both the cellular arm, comprised of innate immunity cells, and the soluble arm, whose major component is the complement cascade (ComC). In addition, several mediators released by innate immunity cells, including inflammatory cytokines and small antimicrobial cationic peptides, affect hematopoiesis. There are intriguing observations that HSPCs and immune cells share several cell-surface pattern-recognition receptors (PRRs), such as Toll-like receptors (TLRs) and cytosol-expressed NOD, NOD-like, and RIG-I-like receptors and thus can be considered “pathogen sensors”. In addition, not only lymphocytes but also HSPCs express functional intracellular complement proteins, defined as complosome which poses challenging questions for further investigation of the intracellular ComC-mediated intracrine regulation of hematopoiesis.

Circulating microRNA-197-3p as a potential biomarker for asbestos exposure

Asbestos is considered the main cause of diseases in workers exposed to this mineral in the workplace as well as an environmental pollutant. The association between asbestos and the onset of different diseases has been reported, but asbestos exposure specific biomarkers are not known. MicroRNAs (miRNAs) are small, single-strand, non-coding RNAs, with potential value as diagnostic, prognostic, and predictive markers in liquid biopsies. Sera collected from workers ex-exposed to asbestos (WEA) fibers were compared with sera from healthy subjects (HS) of similar age, as liquid biopsies. The expression of the circulating miRNA 197-3p was investigated employing two different highly analytical PCR methods, i.e. RT-qPCR and ddPCR. MiR-197-3p levels were tested in sera from WEA compared to HS. MiR-197-3p tested dysregulated in sera from WEA (n = 75) compared to HS (n = 62). Indeed, miR-197-3p was found to be 2.6 times down-regulated in WEA vs. HS (p = 0.0001***). In addition, an inverse correlation was detected between miR-197-3p expression level and cumulative asbestos exposure, being this miRNA down-regulated 2.1 times in WEA, with high cumulative asbestos exposure, compared to WEA with low exposure (p = 0.0303*). Circulating miR-197-3p, found to be down regulated in sera from WEA, is proposed as a new potential biomarker of asbestos exposure.

Scaling a Community-Wide Campaign Intervention to Manage Hypertension and Weight Loss

Public health impacts can be achieved when evidence-based interventions are implemented to those most in need. Too often implementation never or slowly occurs. The community-wide campaign intervention Tu Salud ¡Si Cuenta! has evidence of improving health outcomes related to chronic disease among low-income, Latinos. Using the RE-AIM Framework, this study examined if the scaled-up version of the intervention is associated with improvements in hypertension and obesity in 12 locations. Each element of the RE-AIM framework was examined. For “Effectiveness,” we examined outcomes overall and by implementing location. We used linear and logistic regression to assess if exposure in the intervention was associated with improvement in hypertension and weight loss. Participants were stratified into “low exposure” (2–3 outreach visits) vs. “high exposure” (4–5 outreach visits). Based on the RE-AIM Framework, the intervention “reached” its intended population of low-income Latinos, demonstrated “effectiveness” in improving hypertension and obesity, was “adopted” at a high level in all but one site, was “implemented” with fidelity to the intervention model with moderate success across locations, and showed high “maintenance” over time. For effectiveness specifically, we found that out of 5,019 participants, 2,508 (50%) had a baseline hypertensive blood pressure (BP) reading. Of the 2,508, 1,245 (49.9%) recovered to normal blood pressure or pre-hypertension stage by last follow-up. After adjusting for baseline BP and potential confounders in multivariable linear regression models, the high exposure group had significantly more reduction in systolic BP (adjusted mean difference in % change = −0.96; p = 0.002) and diastolic BP (adjusted mean difference in % change = −1.61; p < 0.0001) compared to the low exposure group. After controlling for baseline weight and other confounders, the high exposure group had significantly greater decrease in weight compared to the low exposure group (adjusted mean difference in % change = −1.28; p < 0.0001). Results from the multivariable logistic regression models indicated that compared to the low exposure group the high exposure group was more likely to achieve a clinically significant minimum 5% weight loss [adjusted odds ratio (OR) = 2.97; p < 0.0001). This study contributes evidence that a Community-Wide Campaign model holds promise for addressing hypertension and obesity among low-income Latinos.

Bedaquiline exposure in pregnancy and breastfeeding in women with rifampicin-resistant tuberculosis

Aim We aimed to explore the effect of pregnancy on bedaquiline pharmacokinetics and describe bedaquiline exposure in the human milk of mothers treated for rifampicin-resistant TB, where there is no human data available. Methods We performed a longitudinal pharmacokinetic study in pregnant women treated for rifampicin-resistant TB to explore the effect of pregnancy on bedaquiline exposure. Pharmacokinetic sampling was performed at four time-points over six hours in the third trimester, and again at approximately six weeks postpartum. We obtained serial human milk samples from breastfeeding mothers, and a single plasma sample taken from breastfed and non-breastfed infants to assess bedaquiline exposure. We used liquid chromatography-tandem mass spectrometry to perform the human milk and plasma bedaquiline assays, and population pharmacokinetic modelling to interpret the bedaquiline concentrations. Results We recruited 13 women, six of whom completed the ante- and post-partum PK sampling. All participants were HIV-positive on antiretroviral therapy. We observed lower ante- and post-partum bedaquiline exposures than reported in non-pregnant controls. Bedaquiline concentrations in human milk were higher than maternal plasma (milk to maternal plasma ratio: 24:1). A single random plasma bedaquiline and M2 concentration was available in four infants (median age: 6.5 weeks): concentrations in the one breastfed infant were similar to maternal plasma concentrations; concentrations in the three non-breastfed infants were detectable but lower than maternal plasma concentrations. Conclusion We report low exposure of bedaquiline in pregnant women treated for rifampicin-resistant TB. Bedaquiline significantly accumulates in human milk; breastfed infants receive mg/kg doses of bedaquiline equivalent to maternal doses.

Circulating microRNA-197-3p as a potential biomarker for asbestos exposure

Asbestos is considered the main cause of diseases in workers exposed to this mineral in the workplace as well as an environmental pollutant. The association between asbestos and the onset of different diseases has been reported, but asbestos exposure specific biomarkers are not known. MicroRNAs (miRNAs) are small, single-strand, non-coding RNAs, with potential value as diagnostic, prognostic, and predictive markers in liquid biopsies. Sera collected from workers ex-exposed to asbestos (WEA) fibers were compared with sera from healthy subjects (HS) of similar age, as liquid biopsies. The expression of the circulating miRNA 197-3p was investigated employing two different highly analytical PCR methods, i.e. RT-PCR and dd-PCR. MiR-197-3p levels were tested in sera from WEA compared to HS. MiR-197-3p tested dysregulated in sera from WEA (n=75) compared to HS (n=62). Indeed, miR-197-3p was found to be 2.6 times down-regulated in WEA vs. HS (p=0.0001***). In addition, an inverse correlation was detected between miR-197-3p expression level and cumulative asbestos exposure, being this miRNA down-regulated 2.1 times in WEA, with high cumulative asbestos exposure, compared to WEA with low exposure (p=0.0303*). Circulating miR-197-3p, found to be down regulated in sera from WEA, is proposed as a new potential biomarker of asbestos exposure.

U.S. Housing as a Global Safe Asset: Evidence from China Shocks

This paper demonstrates that the measured stock of China's holding of U.S. assets could be much higher than indicated by the U.S. net international investment position data due to unrecorded historical Chinese in ows into an increasingly popular global safe haven asset: U.S. residential real estate. We first use aggregate capital ows data to show that the increase in unrecorded capital in ows in the U.S. balance of payment accounts over the past decade is mainly linked to in ows from China into U.S. housing markets. Then, using a unique web traffic dataset that provides a direct measure of Chinese demand for U.S. housing at the zip code level, we estimate via a difference-in-difference matching framework that house prices in major U.S. cities that are highly exposed to demand from China have on average grown 7 percentage points faster than similar neighborhoods with low exposure over the period 2010-2016. These average excess price growth gaps co-move closely with macro-level measures of U.S. capital in ows from China, and tend to widen following periods of economic stress in China, suggesting that Chinese households view U.S. housing as a safe haven asset.

Low Exposure Extended Dosing Mimicking Clinical Exposures of the Oral Formulation of Azacitidine Results in a Sustained Hypomethylation and Targets Leukemic Stem Cells

Acute Myeloid Leukemia (AML) is characterized by uncontrolled proliferation of incompletely differentiated myeloid stem/ progenitor cells. Despite recent advances in therapy, high rates of clinical relapse, even in patients who achieve complete remission, remains a critically unmet need. One of the strategies to prolong remission post-induction in AML is to employ effective maintenance therapies. Oral Azacitidine (Oral-AZA; CC-486) is the first and only currently approved maintenance therapy in AML. However, the mechanism of action of Oral-AZA and whether it is differentiated from the Injectable-AZA used in AML induction therapy, remains unclear. In this work, we explore the mechanism of Oral-AZA by in vitro modelling of the relative clinical exposures of Oral-AZA vs Injectable-AZA in AML cell line models. Following Vu et al (Nat. Commun. 2020), we used the Injectable-AZA concentration (1 μM aZA) as a single dose (HELD - High Exposure Limited Duration). A fractionated dose of 0.2 μM each day over 5 days (LEED - Low Exposure Extended Duration) was used to model Oral-AZA. Azacitidine incorporates into RNA and DNA of AML cells leading to hypomethylation driven gene expression changes. We found that HELD but not LEED dosing produced an acute anti-proliferative effect in sensitive AML cell lines suggesting potential for a non-hypomethylation mediated/integrated stress response (ISR) driven mechanism. This ISR effect was rescued by co-treatment with ISRIB, an ISR inhibitor. With HELD, we observed robust ATF4 activation as early as 6 hours that was sustained up to 24 hours. In contrast, LEED induced modest and transient ATF4 activation. Thus, an Injectable-AZA-like regimen activated the ISR pathway more robustly than an Oral-AZA-like regimen. Interestingly, decitabine, a DNA-only incorporating cytidine analog did not activate ISR. In AML cell lines, the target of Azacitidine, DNMT1 was depleted (about 90% compared to control) within 24 hours in both HELD and LEED regimens. However, LEED produced a more sustained DNMT1 loss, up to 7 days whereas in HELD, DNMT1 protein levels recovered 96 hours post-dosing. Given the relative level and duration of DNMT1 loss, we hypothesized that LEED would lead to a more durable hypomethylation. We performed whole genome bisulfite sequencing (WGBS) in 3 AML cell lines (OCI-AML2, MV-4-11 and SKM1) at 48- and 96-hours post-initiation of HELD and LEED dosing. Consistent with the DNMT1 depletion kinetics, at 48 hours we observed almost 75% global DNA hypomethylation with both HELD and LEED treatments. At 96 hours, HELD demonstrated a recovery effect and reverted to 50% hypomethylation. In contrast, LEED showed up to 85% hypomethylated sites, demonstrating the durability of the hypomethylation mediated by an Oral-AZA-like (LEED) regimen. Next, we explored the effect of Oral-AZA-like dosing in the differentiation of leukemic stem cells (LSCs) towards a more mature phenotype. In an in vitro LSC model (OCI-AML-20) with flow cytometry analysis, LEED dosing resulted in a greater depletion (2-fold more) of LSCs (CD34+/38- or 38 low) and concomitant enrichment of cells with more differentiated phenotype (CD34+/38+) compared to HELD dosing. To further validate these observations at the transcriptomic level, we performed single cell RNAseq in OCI-AML-20 cells at different timepoints (3, 5 and 7 days). Data were analyzed using a classifier to identify leukemic myeloid cell lineages (Van Galen et al., Cell 2019). Compared to untreated cells, at day 7, both LEED and HELD dosing resulted in an increase of GMP and promonocytes and those differences were more pronounced with Oral-AZA-like (50% GMP and 20% promonocytic) than the Injectable-AZA-like regimen (28% GMP and 12.5% promonocytic). Taken together, our in vitro modeling of the clinically relevant exposures of Oral-AZA vs Injectable-AZA by using HELD and LEED dosing strategies show a shift of the molecular mechanism between the clinical entities. Our work demonstrates that an Injectable-AZA-like regimen mediates cytotoxicity through an early ISR driven effect. Oral-AZA mechanism leads to a more sustained pharmacodynamic DNA hypomethylation effect that in turn could be linked to a differentiation inducing effect on the LSC population. Disclosures Jeyaraju: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Alapa: Bristol Myers Squibb: Current Employment. Polonskaia: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Risueño: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties. Ahsan: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Wang: Bristol Myers Squibb: Current Employment. Subramanyam: Bristol Myers Squibb: Current Employment. Sriganesh: Bristol Myers Squibb: Current Employment. Anand: Bristol Myers Squibb: Current Employment. Jain: Bristol Myers Squibb: Current Employment. Reddy: Bristol Myers Squibb: Current Employment. Ghosh: Bristol Myers Squibb: Current Employment. Kyriakopoulos: Bristol Myers Squibb: Current Employment. Lailler: Rancho Biosciences: Current Employment. Hartl: Rancho Biosciences: Current Employment. Lopes de Menezes: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties. Hagner: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Thakurta: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties.

Seroprevalence of Toxoplasma gondii in Pinnipeds under Human Care and in Wild Pinnipeds

Toxoplasma gondii infection has been reported in numerous species of marine mammals, some of them with fatal consequences. A serosurvey for T. gondii infection was conducted in pinnipeds from an oceanographic park in Portugal (n = 60); stranded pinnipeds on the Portuguese coast (n = 10); and pinnipeds captured in Lorenzensplate, Germany (n = 99). Sera from 169 pinnipeds were tested for the presence of antibodies to T. gondii by the modified agglutination test with a cut-off titre of 25. An overall seroprevalence of 8.9% (95% confidence interval: 5.1–14.2) was observed. Antibody titres of 25, 50, 100, 1600 and ≥3200 were found in five (33.3%), two (13.3%), five (33.3%), one (6.7%) and two (13.3%) animals, respectively. Pinnipeds under human care had a seroprevalence of 20.0% (12/60), in contrast to 2.8% (3/109) in wild pinnipeds (p < 0.001). General results suggest a low exposure of wild pinnipeds to T. gondii, while the seroprevalence found in pinnipeds under human care highlights the importance of carrying out further studies. This is the first serological survey of T. gondii in pinnipeds in Portugal and the first infection report in South African fur seal (Arctocephalus pusillus pusillus).