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2022 ◽  
Vol 40 (2) ◽  
pp. 1-29
Xinyi Dai ◽  
Yunjia Xi ◽  
Weinan Zhang ◽  
Qing Liu ◽  
Ruiming Tang ◽  

Learning to rank from logged user feedback, such as clicks or purchases, is a central component of many real-world information systems. Different from human-annotated relevance labels, the user feedback is always noisy and biased. Many existing learning to rank methods infer the underlying relevance of query–item pairs based on different assumptions of examination, and still optimize a relevance based objective. Such methods rely heavily on the correct estimation of examination, which is often difficult to achieve in practice. In this work, we propose a general framework U-rank+ for learning to rank with logged user feedback from the perspective of graph matching. We systematically analyze the biases in user feedback, including examination bias and selection bias. Then, we take both biases into consideration for unbiased utility estimation that directly based on user feedback, instead of relevance. In order to maximize the estimated utility in an efficient manner, we design two different solvers based on Sinkhorn and LambdaLoss for U-rank+ . The former is based on a standard graph matching algorithm, and the latter is inspired by the traditional method of learning to rank. Both of the algorithms have good theoretical properties to optimize the unbiased utility objective while the latter is proved to be empirically more effective and efficient in practice. Our framework U-rank+ can deal with a general utility function and can be used in a widespread of applications including web search, recommendation, and online advertising. Semi-synthetic experiments on three benchmark learning to rank datasets demonstrate the effectiveness of U-rank+ . Furthermore, our proposed framework has been deployed on two different scenarios of a mainstream App store, where the online A/B testing shows that U-rank+ achieves an average improvement of 19.2% on click-through rate and 20.8% improvement on conversion rate in recommendation scenario, and 5.12% on platform revenue in online advertising scenario over the production baselines.

2022 ◽  
Vol 8 ◽  
Margot P. J. Visser ◽  
Anton S. M. Dofferhoff ◽  
Jody M. W. van den Ouweland ◽  
Henny van Daal ◽  
Cornelis Kramers ◽  

BackgroundPathology during COVID-19 infection arises partly from an excessive inflammatory response with a key role for interleukin (IL)-6. Both vitamin D and K have been proposed as potential modulators of this process.MethodsWe assessed vitamin D and K status by measuring circulating 25-hydroxyvitamin D (25(OH)D) and desphospho-uncarboxylated Matrix Gla-Protein (dp-ucMGP), respectively in 135 hospitalized COVID-19 patients in relation to inflammatory response, elastic fiber degradation and clinical outcomes.ResultsComparing good and poor disease outcomes of COVID-19 patients, vitamin 25(OH)D levels were not significantly different. IL-6 levels, however, were significantly higher in patients with poor outcome, compared to patients with good outcome (30.3 vs. 153.0 pg/mL; p < 0.0001). Dp-ucMGP levels as biomarker of extrahepatic vitamin K status was associated with IL-6 levels (r = 0.35; p < 0.0001). In contrast, 25(OH)D levels were only borderline statistically significant correlated with IL-6 (r = −0.14; p <0.050). A significant association was also found between IL-6 and elastic fiber degradation. Contrary to vitamin K status, 25(OH)D did not correlate with elastic fiber degradation.ConclusionsDp-ucMGP associates with IL-6 as a central component of the destructive inflammatory processes in COVID-19. An intervention trial may provide insight whether vitamin K administration, either or not in combination with vitamin D, improves clinical outcome of COVID-19.

Science ◽  
2022 ◽  
Vol 375 (6577) ◽  
pp. 221-225
Alex G. Johnson ◽  
Tanita Wein ◽  
Megan L. Mayer ◽  
Brianna Duncan-Lowey ◽  
Erez Yirmiya ◽  

Ancient origin of cell death Gasdermins are cell death proteins in mammals that form membrane pores in response to pathogen infection. Johnson et al . report that diverse bacteria encode structural and functional homologs of mammalian gasdermins. Like their mammalian counterparts, bacterial gasdermins are activated by caspase-like proteases, oligomerize into large membrane pores, and defend against pathogen—in this case, bacteriophage—infection. Proteolytic activation occurs through the release of a short inhibitory peptide, and many bacterial gasdermins are lipidated to facilitate membrane pore formation. Pyroptotic cell death, a central component of mammalian innate immunity, thus has a shared origin with an ancient antibacteriophage defense system. —SMH

2022 ◽  
Qian Wu ◽  
Euclides Sacomboio ◽  
Lara V Souza ◽  
Rui Martins ◽  
Silvia Cardoso ◽  

Anemia is a clinical hallmark and independent risk factor of malaria caused by Plasmodium spp. infection. While it is known that anemia arises from parasite-induced hemolysis, whether and how host metabolic adaptation to malaria regulate anemia severity is less understood. Here we demonstrate that reprogramming of renal iron (Fe) metabolism is a central component of the host metabolic response regulating the pathogenesis of life-threatening malarial anemia. Renal proximal tubule epithelial cells (RPTEC) are the main cell compartment responsible for Fe storage and recycling during Plasmodium infection in mice. Transcriptional reprogramming of RPTEC couples immune resistance to Plasmodium infection to renal Fe export via the induction of the cellular Fe exporter SLC40A1/ferroportin 1. This integrated defense strategy is essential to deliver Fe to erythroblasts and support compensatory erythropoiesis to prevent the development of life-threatening anemia. Failure to mobilize Fe from RPTEC causes AKI and is associated with life-threatening anemia in P. falciparum-infected individuals. These findings reveal an unexpected role of the kidneys in the control of organismal Fe metabolism during malaria.

2022 ◽  
Vol 12 (1) ◽  
pp. 84
Kaoru Kinugawa ◽  
Tomoo Mano ◽  
Yuya Yamatani ◽  
Toshiteru Miyasaka ◽  
Hiroshi Kataoka ◽  

Patients with Parkinson’s disease (PD) often experience pain, which fluctuates in “on” and “off” states, but the underlying mechanism is unclear. The nucleus accumbens (NAc) is a central component of the mesolimbic dopaminergic pathway involved in pain processing. We conducted resting-state functional magnetic resonance imaging (rsfMRI) analysis to explore the relationship between the neuronal synchronization of NAc with pain-related brain regions and pain intensity in “on” and “off” states. We assessed 23 patients with sporadic PD based on rsfMRI and pain intensity using the revised Short-Form McGill Pain Questionnaire. Patients with PD displayed higher pain intensity scores in the “off” state than in the “on” state. The pain intensity in the “off” state was substantially correlated with the functional connectivity (FC) between the NAc and primary motor/sensory cortices and contralateral NAc. Changes in pain intensity from the “on” to “off” state displayed correlations with those between the right (rNA) and left NAc (lNAc) and the right precentral gyrus (rPreCG) /right insular cortex (rIC) from the “off” to “on” state. Aberrant bilateral NAc and rNAc–rPreCG/rIC FC in the “off” state were closely related to pain symptoms developed from the “on” to “off” states. These results suggest that the NAc in the mesolimbic pathway is related to pain in PD and may help understand the mechanism of pain development in patients with PD.

2022 ◽  
pp. 0095327X2110649
Aluma Kepten

How does secrecy shape narratives of militarized hegemonic masculinity? This article assesses a gap at the intersection between theories of masculinities and organizational secrecy. Supported by 15 interviews with current and former male workers of a covert section of an Israeli national security organization, it argues that secrecy is experienced as both an external hurdle and a central component to the way that men internalize masculinity. Unable to access social capital outside the security organization, the respondents of the study construct a social field inside it through which they can assert their masculinity. They do so by conceptualizing their jobs, themselves, and the organization through a prism of sacrificial warriorhood, and actively incorporate secrecy’s constraints into a narrative of “super-men”. This study thus examines secrecy in the context of a militarized environment, showing the experience of masculinity and a perceived lack of power-access among members of a dominant group.

eLife ◽  
2022 ◽  
Vol 11 ◽  
Daniel Walter McKay ◽  
Heather E McFarlane ◽  
Yue Qu ◽  
Apriadi Situmorang ◽  
Matthew Gilliham ◽  

Plant cells maintain a low luminal pH in the Trans-Golgi-Network/Early Endosome (TGN/EE), the organelle in which the secretory and endocytic pathways intersect. Impaired TGN/EE pH regulation translates into severe plant growth defects. The identity of the proton pump and proton/ion antiporters that regulate TGN/EE pH have been determined, but an essential component required to complete the TGN/EE membrane transport circuit remains unidentified - a pathway for cation and anion efflux. Here, we have used complementation, genetically encoded fluorescent sensors, and pharmacological treatments to demonstrate that Arabidopsis Cation Chloride Cotransporter (CCC1) is this missing component necessary for regulating TGN/EE pH and function. Loss of CCC1 function leads to alterations in TGN/EE-mediated processes including endocytic trafficking, exocytosis and response to abiotic stress, consistent with the multitude of phenotypic defects observed in ccc1 knockout plants. This discovery places CCC1 as a central component of plant cellular function.

2022 ◽  
Vol 12 ◽  
Tobias Heinen ◽  
Chen Xie ◽  
Maryam Keshavarz ◽  
Dominik Stappert ◽  
Sven Künzel ◽  

Map2k7 (synonym Mkk7) is a conserved regulatory kinase gene and a central component of the JNK signaling cascade with key functions during cellular differentiation. It shows complex transcription patterns, and different transcript isoforms are known in the mouse (Mus musculus). We have previously identified a newly evolved testis-specific transcript for the Map2k7 gene in the subspecies M. m. domesticus. Here, we identify the new promoter that drives this transcript and find that it codes for an open reading frame (ORF) of 50 amino acids. The new promoter was gained in the stem lineage of closely related mouse species but was secondarily lost in the subspecies M. m. musculus and M. m. castaneus. A single mutation can be correlated with its transcriptional activity in M. m. domesticus, and cell culture assays demonstrate the capability of this mutation to drive expression. A mouse knockout line in which the promoter region of the new transcript is deleted reveals a functional contribution of the newly evolved promoter to sperm motility and the spermatid transcriptome. Our data show that a new functional transcript (and possibly protein) can evolve within an otherwise highly conserved gene, supporting the notion of regulatory changes contributing to the emergence of evolutionary novelties.

2022 ◽  
Frank Milton Delgado-Cáceres ◽  
Kevin Angel Silva-Parra ◽  
Alejandra Torres-Slimming

Abstract BackgroundImmigrants arriving in a new country face changes that affect their social, employment, and migratory status. We carried out a mixed methods study in the rapidly growing Venezuelan immigrant population in Lima, Peru. The objective was to determine whether there was an association between time in Peru and self-perception of symptom distress (SD), interpersonal relationships (IR), and social role (SR). MethodsThe quantitative central component consisted of a cross-sectional study, surveying 152 participants using the Outcome Questionnaire 45.2 (OQ-45.2). The qualitative component, based on phenomenology, explored experiences and challenges during the migration process. Semi-structured in-depth interviews were done in 16 informants.ResultsAn association that was observed was the increase in the risk of clinically significant SR score with additional years of age. All informants mentioned having witnessed or experienced xenophobia in Peru. Every informant stated that significant labor differences existed between the countries. The most reported somatic symptoms were symptoms of anxiety and alterations of sleep. Additionally, no informant expressed a desire to remain in Peru long term. ConclusionsA minority of participants registered a clinically significant total and domain score. No association between months in Lima and the self-perception of distress was found. However, this could be due to the short amount of time spent in Peru and any change in self-perception might only be perceived after years or decades spent in Peru. This study is one of the first to use mixed methods to explore the mental health of the immigrant Venezuelan population.

2022 ◽  
Vol 12 ◽  
Gerard J. Gianoli

Dizziness is a frequent complaint after head trauma. Among patients who suffer a concussion (mild traumatic brain injury or mTBI), dizziness is second only to headache in symptom frequency. The differential diagnosis of post-concussive dizziness (PCD) can be divided into non-vestibular, central vestibular and peripheral vestibular causes with growing recognition that patients frequently exhibit both central and peripheral findings on vestibular testing. Symptoms that traditionally have been ascribed to central vestibular dysfunction may be due to peripheral dysfunction. Further, our ability to test peripheral vestibular function has improved and has allowed us to identify peripheral disorders that in the past would have remained unnoticed. The importance of the identification of the peripheral component in PCD lies in our ability to remedy the peripheral vestibular component to a much greater extent than the central component. Unfortunately, many patients are not adequately evaluated for vestibular disorders until long after the onset of their symptoms. Among the diagnoses seen as causes for PCD are (1) Central vestibular disorders, (2) Benign Paroxysmal Positional Vertigo (BPPV), (3) Labyrinthine dehiscence/perilymph fistula syndrome, (4) labyrinthine concussion, (5) secondary endolymphatic hydrops, (6) Temporal bone fracture, and (7) Malingering (particularly when litigation is pending). These diagnoses are not mutually exclusive and PCD patients frequently exhibit a combination of these disorders. A review of the literature and a general approach to the patient with post-concussive dizziness will be detailed as well as a review of the above-mentioned diagnostic categories.

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