Additive Fashion Research Articles

Leveraging Dual-Ligase Recruitment to Enhance Protein Degradation via a Heterotrivalent Proteolysis Targeting Chimera.

Proteolysis targeting chimera (PROTAC) degraders are typically bifunctional with one E3 ligase ligand connected to one target protein ligand via a linker. While augmented valency has been shown with trivalent PROTACs targeting two binding sites within a given target protein, or used to recruit two different targets, the possibility of recruiting two different E3 ligases within the same compound has not been demonstrated. Here we present dual-ligase recruitment as a strategy to enhance targeted protein degradation. We designed heterotrivalent PROTACs composed of CRBN, VHL and BET targeting ligands, separately tethered via a branched trifunctional linker. Structure-activity relationships of 12 analogues qualifies AB3067 as the most potent and fastest degrader of BET proteins, with minimal E3 ligase cross-degradation. Comparative kinetic analyses in wild-type and ligase single and double knockout cell lines revealed that protein ubiquitination and degradation induced by AB3067 was contributed to by both CRBN and VHL in an additive fashion. We further expand the scope of the dual-ligase approach by developing a heterotrivalent CRBN/VHL-based BromoTag degrader and a tetravalent PROTAC comprising of two BET ligand moieties. In summary, we provide proof-of-concept for dual-E3 ligase recruitment as a strategy to boost degradation fitness by recruiting two E3 ligases with a single degrader molecule. This approach could potentially delay the outset of resistance mechanisms involving loss of E3 ligase functionality.

Exploring Trust Ecology in a Public-Private Partnership for Agricultural Innovation in the United States Bioeconomy

United States (US) federal agencies are endorsing public-private partnerships (PPPs) to link public institutions with industry to develop local supplies of biofuel and build a domestic bioeconomy. Although trust is a critical factor within effective PPPs, few studies have addressed the different types of trust needed to cultivate these partnerships. Employing a mixed-method design, we explore a PPP in the Southeast US through the lens of trust ecology. We describe how participants perceive trust types within different project spaces and how trust changed during the partnership. Our findings highlight the role that different interactive spaces can play in cultivating types of trust that accumulate in an additive fashion. We offer insights on process-design mechanisms and project management strategies that can bolster trust in PPPs.

How Encephalopathy Impacts Language Ability: A Scoping Review of the Linguistic Abilities of Adults with Developmental and Epileptic Encephalopathy.

Background and Objectives: Developmental and epileptic encephalopathy refers to a group of conditions where patients experience abnormal development due to various causes as well as frequent epileptiform discharges that ultimately contribute, in an independent and additive fashion, to cognitive and linguistic impairments. The language and cognition outcome of these patients in adulthood has been understudied. This paper aims to present a scoping review of linguistic abilities in adults with developmental and epileptic encephalopathy to determine the extent to which language outcomes in adulthood and their relation to cognitive outcomes have been studied. Design: Two online databases were searched and the methodological framework by Arksey & O'Malley (2005) was adopted. Results: Out of the 27 selected studies, only 13 exclusively examined adults, 15 were group studies, 5 were case studies and 7 were case series. A total of 9 out of the 15 group studies provided individual results for adults. Twenty-two studies included a follow-up examination. Twenty-three studies addressed the relationship between language and cognition. The selected studies indicate the presence of language impairments, which are nevertheless differentially manifested in the syndromes under investigation, whereas individual variability is also reported. Aspects of cognition seem to correlate with linguistic abilities. Conclusions: In sum, despite variability in linguistic abilities, language deficits constitute a significant aspect of the clinical profile of many adults with developmental and epileptic encephalopathy, a finding that should be taken into account for the treatment protocols of these individuals.

Impact of difficult biliary cannulation on post-ERCP pancreatitis: secondary analysis of the stent versus indomethacin trial dataset

Background and AimsDifficult biliary cannulation (DBC) is a known risk factor for developing post-ERCP pancreatitis (PEP). To better understand how DBC increases PEP risk, we examined the interplay between technical aspects of DBC and known PEP risk factors. MethodsThis was a secondary analysis of a multicenter, randomized controlled trial comparing rectal indomethacin alone with the combination of rectal indomethacin and prophylactic pancreatic duct (PD) stent placement for PEP prophylaxis in high-risk patients. Participants were categorized into 3 groups: 1) DBC with high pre-procedure risk for PEP, 2) DBC without high pre-procedure risk, and 3) non-DBC at high pre-procedure risk. ResultsIn all, 1601 (84.1%) participants experienced DBC, which required a mean of 12 (SD 10) cannulation attempts and mean duration of 14.7 minutes (SD 14.9). PEP rate was highest (20.7%) in DBC with high pre-procedure risk, followed by non-DBC with high pre-procedure risk (13.5%) and then DBC without high pre-procedure risk (8.8%). Increasing number of PD-wire passages (aOR:1.97, 95% CI:1.25-3.1) was associated with PEP in DBC, but PD injection, pancreatic sphincterotomy and number of cannulation attempts were not associated with PEP. Combining indomethacin with PD stenting lowered PEP risk (aOR:0.61, 95% CI:0.44-0.84) in DBCs. This protective effect was evident in up to at least 4 PD wire passages. ConclusionsDBC confers higher PEP risk in additive fashion to pre-procedural risk factors. PD wire passages appear to add the greatest PEP risk in DBCs, but combining indomethacin with PD stenting reduces this risk, even with increasing PD wire passages.

Pitch-Tracking Metrics as a Predictor of Future Shoulder and Elbow Injuries in Major League Baseball Pitchers: A Machine-Learning and Game-Theory Based Analysis.

Understanding interactions between multiple risk factors for shoulder and elbow injuries in Major League Baseball (MLB) pitchers is important to identify potential avenues by which risk can be reduced while minimizing impact on player performance. To apply a novel game theory-based approach to develop a machine-learning model predictive of next-season shoulder and elbow injuries in MLB pitchers and use this model to understand interdependencies and interaction effects between the most important risk factors. Case-control study; Level of evidence, 3. Pitcher demographics, workload measures, pitch-tracking metrics, and injury data between 2017 and 2022 were used to construct a database of MLB pitcher-years, where each item in the database corresponded to a pitcher's information and metrics for that year. An extreme gradient boosting machine-learning model was trained to predict next-season shoulder and elbow injuries utilizing Shapley additive explanation values to quantify feature importance as well as interdependencies and interaction effects between predictive variables. A total of 3808 pitcher-years were included in this analysis; 606 (15.9%) of these involved a shoulder or elbow injury resulting in placement on the MLB injured list. Of the >65 candidate features (including workload, demographic, and pitch-tracking metrics), the most important contributors to predicting shoulder/elbow injury were increased: pitch velocity (all pitch types), utilization of sliders (SLs), fastball (FB) spin rate, FB horizontal movement, and player age. The strongest game theory interaction effects were that higher FB velocity did not alter a younger pitcher's predicted risk of shoulder/elbow injury versus older pitchers, risk of shoulder/elbow injury increased with the number of high-velocity pitches thrown (regardless of pitch type and in an additive fashion), and FB velocity <95 mph (<152.9 kph) demonstrated strong negative interaction effects with higher SL percentage, suggesting that the overall predicted risk of injury for pitchers throwing a high number of SLs could be attenuated by lower FB velocity. Pitch-tracking metrics were substantially more predictive of future injury than player demographics and workload metrics. There were many significant game theory interdependencies of injury risk. Notably, the increased risk of injury that was conferred by throwing with a high velocity was even further magnified if the pitchers were also older, threw a high percentage of SLs, and/or threw a greater number of pitches.

Regioselective Annulation of 6-Carboxy-Substituted Pyrones as a Two-Carbon Unit in Formal [4 + 2] Cycloaddition Reactions.

Heterocycles serve as a critical motif in chemistry, but despite being present in more than 85% of pharmaceuticals, there are limited methods for their construction. Here, we describe the incorporation of intact pyrone (2H-pyran-2-one) into larger ring systems via annulation. In a formal [4 + 2] cycloaddition, the pyrone regioselectively accepts a benzylic anion as a nucleophile in a conjugate addition fashion, with the subsequent pyrone-derived enolate attaching to a pendant ester on the initial nucleophile. Subsequent base-driven enolate formation and elimination establish aromaticity of the newly formed ring. After optimization of this process using an NMR-based assessment to overcome solubility and separation challenges, the reaction was successfully applied to a library of 6-ester and -amide-substituted pyrones and using a phenyl ester and other substituted sulfoxides. This technology enables the incorporation of intact pyrone rings into more complex systems, such as for the total synthesis of the natural product thermorubin.

Additive and Moderating Effect of Parents and Friends on Health and Behavior Outcomes During Emerging Adulthood

Relationships with parents and friends may work together to increase the risk of adjustment problems in emerging adulthood. However, it is still undetermined if social relationships act in an additive (i.e., serve as unique predictors) or moderating (i.e., interact with other predictors) fashion. In a cross-sectional sample of 859 female college students ( M age = 19.53, SD = 1.49; 73.9% White) from a large university in the south-central United States, we assessed how parents and best friends impact emerging adult internalizing symptoms, risky behavior, and health problems. We found that low levels of best friend risky behavior attenuated the links between father-emerging adult relationship quality and risky behavior and internalizing symptoms, and high levels of father-emerging adult relationship quality magnified the association between mother-emerging adult relations and internalizing symptoms. Ultimately, these results indicate that relationships with parents and friends served as additive or unique predictors of emerging adult health and behavior.

Relationships between lung function, allergy, and wheezing in urban children

BackgroundAllergic sensitization and low lung function in early childhood are risk factors for subsequent wheezing and asthma. However, it is unclear how allergic sensitization impacts lung function over time. ObjectiveTo test whether allergy influences lung function and whether these factors synergistically increase the risk of continued wheezing in childhood. MethodsWe analyzed longitudinal measurements of lung function (spirometry, impulse oscillometry) and allergic sensitization (aeroallergen skin tests, serum allergen-specific IgE) throughout early childhood in the Urban Environmental and Childhood Asthma study which included high-risk urban children living in disadvantaged neighborhoods. Intraclass correlation coefficients (ICC) were calculated to assess lung function stability. Cluster analysis identified low, medium, and high allergy trajectories, which were compared to lung function and wheezing episodes in linear regression models. A variable selection model assessed predictors at age 5 for continued wheezing through age 12. ResultsLung function adjusted for growth was stable (ICC 0.5–0.7) from ages 5–12 years and unrelated to allergy trajectory. Lung function and allergic sensitization were associated with wheezing episodes in an additive fashion. In children with asthma, measuring lung function at age 5 added little to the medical history for predicting future wheezing episodes through age 12. ConclusionIn high-risk urban children, age-related trajectories of allergic sensitization were not associated with lung function development, however, both indicators were related to continued wheezing. These results underscore the importance of understanding early life factors that negatively impact lung development and suggest that treating allergic sensitization may not alter lung function development in early to mid-childhood.

GZ17-6.02 interacts with proteasome inhibitors to kill multiple myeloma cells.

GZ17-6.02, a synthetically manufactured compound containing isovanillin, harmine and curcumin, has undergone phase I evaluation in patients with solid tumors (NCT03775525) with a recommended phase 2 dose (RP2D) of 375 mg PO BID. GZ17-6.02 was more efficacious as a single agent at killing multiple myeloma cells than had previously been observed in solid tumor cell types. GZ17-6.02 interacted with proteasome inhibitors in a greater than additive fashion to kill myeloma cells and alone it killed inhibitor-resistant cells to a similar extent. The drug combination of GZ17-6.02 and bortezomib activated ATM, the AMPK and PERK and inactivated ULK1, mTORC1, eIF2α, NFκB and the Hippo pathway. The combination increased ATG13 S318 phosphorylation and the expression of Beclin1, ATG5, BAK and BIM, and reduced the levels of BCL-XL and MCL1. GZ17-6.02 interacted with bortezomib to enhance autophagosome formation and autophagic flux, and knock down of ATM, AMPKα, ULK1, Beclin1 or ATG5 significantly reduced both autophagy and tumor cell killing. Knock down of BAK and BIM significantly reduced tumor cell killing. The expression of HDACs1/2/3 was significantly reduced beyond that previously observed in solid tumor cells and required autophagy. This was associated with increased acetylation and methylation of histone H3. Combined knock down of HDACs1/2/3 caused activation of ATM and the AMPK and caused inactivation of ULK1, mTORC1, NFκB and the Hippo pathway. HDAC knock down also enhanced ATG13 phosphorylation, increased BAK levels and reduced those of BCL-XL. Collectively, our present studies support performing additional in vivo studies with multiple myeloma cells.

Catalytic Enantioselective Aminative Difunctionalization of Alkenes.

Enantioselective difunctionalization of alkenes offers a straightforward means for the rapid construction of enantioenriched complex molecules. Despite the tremendous efforts devoted to this field, enantioselective aminative difunctionalization remains a challenge, particularly through an electrophilic addition fashion. Herein, we report an unprecedented approach for the enantioselective aminative difunctionalization of alkenes via copper-catalyzed electrophilic addition with external azo compounds as nitrogen sources. A series of valuable cyclic hydrazine derivatives via either [3 + 2] cycloaddition or intramolecular cyclization have been achieved in high chemo-, regio-, enantio-, and diastereoselectivities. In this transformation, a wide range of functional groups, such as carboxylic acid, hydroxy, amide, sulfonamide, and aryl groups, could serve as nucleophiles. Importantly, a new cyano oxazoline chiral ligand was found to play a crucial role in the control of enantioselectivity.

Interaction effect of type 2 diabetes mellitus and hypertension on left atrial function: a three-dimensional echocardiography study.

Type 2 diabetes mellitus (T2DM) and hypertension (HT) often coexist and contribute to left atrial (LA) functional abnormalities. The aim of the present study was to explore whether there is a potential interaction effect between T2DM and HT on LA function. A total of 135 patients (45 with T2DM only, 45 with HT only, and 45 with both T2DM and HT) were enrolled and compared to 45 age- and sex-matched controls. LA volume fraction, including LA ejection fraction (LAEF), LA expansion index (LAEI), LA passive emptying fraction (LAPEF), and LA active emptying fraction (LAAEF), and strain parameters, including LA reservoir longitudinal strain (LASr), LA conduit longitudinal strain (LAScd), and LA contraction longitudinal strain (LASct), were obtained using three-dimensional echocardiography (3DE). Patients with T2DM had significantly more impaired LA reservoir and conduit functions compared to those without T2DM (P<0.05), and patients with HT had a significantly more impaired LA reservoir function, conduit function, and booster pump function compared to those without HT (P<0.05). Two-way analysis of variance showed that there were significant additive interaction effects between T2DM and HT with respect to LASr (PT2DM + HT =0.002) and LAScd (PT2DM + HT =0.001). Generalized linear model demonstrated that T2DM + HT had a greater relative contribution than either T2DM or HT alone to the LA strain indexes, even after adjustment for other confounders (LASr, βT2DM + HT =-3.931, 95% CI: -6.237 to -1.624, P=0.001; LAScd, βT2DM + HT=-3.781, 95% CI: -5.653 to -1.908, P<0.001). Both T2DM and HT had an adverse effect on LA function. The coexistence of both conditions further impaired LA performance in an additive interaction fashion.

The Fusarium graminearum Transporters Abc1 and Abc6 Are Important for Xenobiotic Resistance, Trichothecene Accumulation, and Virulence to Wheat.

The plant pathogenic fungus Fusarium graminearum is the causal agent of Fusarium head blight (FHB) disease on small-grain cereals. F. graminearum produces trichothecene mycotoxins such as deoxynivalenol (DON) that are required for full virulence. DON must be exported outside the cell to cause FHB disease, a process that may require the involvement of membrane-bound transporters. In this study, we show that the deletion of membrane-bound transporters results in reduced DON accumulation as well as reduced FHB symptoms on wheat. Deletion of the ATP-binding cassette (ABC) transporter gene Abc1 results in the greatest reduction in DON accumulation and virulence. Deletion of another ABC transporter gene, Abc6, also reduces FHB symptoms to a lesser degree. Combining deletions fails to reduce DON accumulation or virulence in an additive fashion, even when a ∆abc1 deletion is included. Heterologous expression of F. graminearum transporters in a DON-sensitive strain of yeast confirms Abc1 as a major DON resistance mechanism; furthermore, it suggests that Abc1 is directly participating in DON transport rather than facilitating DON transport though other means. Yeast expression further indicates that multiple transporters, including Abc1, play an important role in resistance to the wheat phytoalexin 2-benzoxazolinone (BOA) and other xenobiotics. Thus, Abc1 may contribute to virulence on wheat both by facilitating export of DON and by providing resistance to the wheat phytoalexin BOA. This research provides useful information that may aid in designing novel management techniques of FHB or other destructive plant diseases.

Combination of MCL-1 and BCL-2 inhibitors is a promising approach for a host-directed therapy for tuberculosis

Tuberculosis (TB) accounts for 1.6 million deaths annually and over 25% of deaths due to antimicrobial resistance. Mycobacterium tuberculosis (M.tb) drives MCL-1 expression (family member of anti-apoptotic BCL-2 proteins) to limit apoptosis and grow intracellularly in human macrophages. The feasibility of re-purposing specific MCL-1 and BCL-2 inhibitors to limit M.tb growth, using inhibitors that are in clinical trials and FDA-approved for cancer treatment has not be tested previously. We show that specifically inhibiting MCL-1 and BCL-2 induces apoptosis of M.tb-infected macrophages, and markedly reduces M.tb growth in human and murine macrophages, and in a pre-clinical model of human granulomas. MCL-1 and BCL-2 inhibitors limit growth of drug resistant and susceptible M.tb in macrophages and act in additive fashion with the antibiotics isoniazid and rifampicin. This exciting work uncovers targeting the intrinsic apoptosis pathway as a promising approach for TB host-directed therapy. Since safety and activity studies are underway in cancer clinics for MCL-1 and BCL-2 inhibitors, we expect that re-purposing them for TB treatment should translate more readily and rapidly to the clinic. Thus, the work supports further development of this host-directed therapy approach to augment current TB treatment.

Pervasive under-dominance in gene expression underlying emergent growth trajectories in Arabidopsis thaliana hybrids

BackgroundComplex traits, such as growth and fitness, are typically controlled by a very large number of variants, which can interact in both additive and non-additive fashion. In an attempt to gauge the relative importance of both types of genetic interactions, we turn to hybrids, which provide a facile means for creating many novel allele combinations.ResultsWe focus on the interaction between alleles of the same locus, i.e., dominance, and perform a transcriptomic study involving 141 random crosses between different accessions of the plant model species Arabidopsis thaliana. Additivity is rare, consistently observed for only about 300 genes enriched for roles in stress response and cell death. Regulatory rare-allele burden affects the expression level of these genes but does not correlate with F1 rosette size. Non-additive, dominant gene expression in F1 hybrids is much more common, with the vast majority of genes (over 90%) being expressed below the parental average. Unlike in the additive genes, regulatory rare-allele burden in the dominant gene set is strongly correlated with F1 rosette size, even though it only mildly covaries with the expression level of these genes.ConclusionsOur study underscores under-dominance as the predominant gene action associated with emergence of rosette growth trajectories in the A. thaliana hybrid model. Our work lays the foundation for understanding molecular mechanisms and evolutionary forces that lead to dominance complementation of rare regulatory alleles.

Cellular responses after (neratinib plus pemetrexed) exposure in NSCLC cells.

We previously demonstrated that neratinib interacted with pemetrexed to kill non-small cell lung cancer (NSCLC) cells. From developing other drug combinations, we observed that several days following exposure, cells activated survival mechanisms to counteract drug toxicity. The present studies attempted to define mechanisms that evolve to reduce the efficacy of neratinib and pemetrexed. Neratinib and pemetrexed synergized to kill NSCLC cells expressing wild-type RAS proteins, mutant KRAS (G12S; Q61H; G12A and G12C) or mutant NRAS (Q61K) or mutant ERBB1 (L858R; L858R T790M and exon 19 deletion). Neratinib and pemetrexed interacted in a greater than additive fashion to kill after 24 h, and after a further 24 h culture in the absence of drugs. Mutant KRAS G12V was more cytoprotective than either activated MEK1 or activated AKT. Knockdown of mutant KRAS reduced drug combination killing at the 48 h timepoint. Despite culture for 24 h in the absence of the drugs, the expression and activities of ERBB1, ERBB2 and ERBB4 remained significantly lower as did the activities of mammalian target of rapamycin (mTOR) C1 and mTORC2. The drug combination reduced KRAS and NRAS levels for 24 h, however, in the absence of the drugs, RAS levels had normalized by 48 h. Expression of Beclin1 and ATG5 remained elevated and of MCL1 and BCL-XL lower. No evolutionary activations of survival signaling by ERBB3, c-KIT, c-MET or PDGFRβ or in intracellular signaling pathways were observed. These findings argue against the development of 'early' resistance mechanisms after neratinib and pemetrexed exposure. Future studies will be required to understand how NSCLC cells become resistant to neratinib and pemetrexed.

Quadruple‐Bidentate Nitrate‐Ligated A2Hg(NO3)4 (A=K, Rb): Strong Second‐Harmonic Generation and Sufficient Birefringence

AbstractThe design of efficient nonlinear optical (NLO) crystals continues to pose significant challenges due to the difficulty of assembling polar NLO‐active modules in an optimal additive fashion. We report herein the first NLO‐active mercuric nitrates A2Hg(NO3)4 (A=(KHNO), Rb (RHNO)), for which assembly is induced by ionic polarization of the d10 cations. The two new crystalline compounds are isostructural, featuring interesting pseudo‐diamond‐like structures with parallel [Hg(NO3)4] modules, and leading to strong powder second‐harmonic generation (SHG) responses of 9.2 (KHNO) and 8.8 (RHNO) times that of KH2PO4. In combination with the simple solution preparation of centimeter‐scale crystals, sufficient birefringence, and short ultraviolet (UV) cutoff edges, these attributes make KHNO and RHNO promising candidates for UV NLO materials. Theoretical calculations and single‐crystal structure analysis reveal that the newly‐developed highly condensed and distorted [Hg(NO3)4] module, with an Hg2+ cation that is quadruply bidentate nitrate‐ligated, is crucial for the significant SHG responses. This work highlights the potential importance of modules with multiple bidentate ligands for the development of high‐performing next‐generation NLO materials.

Quadruple-Bidentate Nitrate-Ligated A2 Hg(NO3 )4 (A=K, Rb): Strong Second-Harmonic Generation and Sufficient Birefringence.

The design of efficient nonlinear optical (NLO) crystals continues to pose significant challenges due to the difficulty of assembling polar NLO-active modules in an optimal additive fashion. We report herein the first NLO-active mercuric nitrates A2 Hg(NO3 )4 (A=(KHNO), Rb (RHNO)), for which assembly is induced by ionic polarization of the d10 cations. The two new crystalline compounds are isostructural, featuring interesting pseudo-diamond-like structures with parallel [Hg(NO3 )4 ] modules, and leading to strong powder second-harmonic generation (SHG) responses of 9.2 (KHNO) and 8.8 (RHNO) times that of KH2 PO4 . In combination with the simple solution preparation of centimeter-scale crystals, sufficient birefringence, and short ultraviolet (UV) cutoff edges, these attributes make KHNO and RHNO promising candidates for UV NLO materials. Theoretical calculations and single-crystal structure analysis reveal that the newly-developed highly condensed and distorted [Hg(NO3 )4 ] module, with an Hg2+ cation that is quadruply bidentate nitrate-ligated, is crucial for the significant SHG responses. This work highlights the potential importance of modules with multiple bidentate ligands for the development of high-performing next-generation NLO materials.

Worker Congresses in China: Do they matter?

AbstractWe use a survey of privately‐owned enterprises spanning the years 2006–2014 and estimate effects of Worker Congresses on worker welfare outcomes. We find that Congresses by themselves had positive effects on all outcomes except for wages. Firms with both a Congress and a union had large and positive effects on all outcomes reflecting the sum of their separate individual effects, suggesting that they were not substitute institutions but rather were complementary in an additive fashion.

COVID-19 and prevalence of venous thromboembolism among cancer patients: A nationwide inpatient sample analysis.

e18839 Background: Cancer, as well as immunosuppression from chemotherapy, aggravates thromboembolism risk. The risk is likely amplified in an additive fashion with COVID-19 infection, which confers a higher risk of VTE risk with viral sepsis, endothelial inflammation, and microthrombi formation. Numerous studies have shown the heightened risk of pulmonary embolism among severe COVID-19 patients. We sought to evaluate further the extent of COVID-19-associated coagulopathy and associated outcomes. Methods: National Inpatient Sample 2020 was used to identify non-elective hospitalizations of patients with a secondary diagnosis of any cancer. These were stratified into two cohorts based on the presence of the primary diagnosis of COVID-19. Primary outcomes include venous thromboembolism, PE, and VTE without PE in cancer patients with and without Covid-19 infection. The secondary outcomes examined were in-patient mortality, the average length of stay (LOS), and total hospital charge (THC). Multivariate analysis was performed to obtain the odds ratio. All weighted analysis was conducted through STATA 17. Results: Out of 1,734,735 non-elective admissions of patients with cancer, 36,295 (2%) were admitted for COVID-19. Our analysis showed statistically non-significant increased odds of venous thromboembolism(aOR:1.09 CI 0.99-1.20) in cancer patients with COVID. There was, however, a significant increase in the odds of pulmonary embolism(aOR 1.7, CI: 1.51- 1.91) among cancer patients with Covid-19. There were decreased odds of VTE without PE(aOR: 0.67 CI: 0.57-0.78). There was a statistically significant increase in odds of mortality (aOR: 2.8 CI: 2.63-3.0), length of stay(aOR:1.85 CI: 1.65- 2.05), total hospital charges($83,201 vs. $78,869 p: &lt; 0.01) in cancer patients with COVID-19 compared to cancer patients without COVID-19. Conclusions: This study shows that COVID-19 in cancer patients has deleterious effects, including an increased risk of pulmonary embolism and poor in-hospital outcomes. The finding of a lower incidence of non-PE VTE in patients with cancer is likely related to limitations with coding in NIS, in which lower complexity codes might be omitted in patients with multiple diagnoses. With significantly increased mortality and economic burden, these findings emphasize the significance of thrombotic prophylaxis and vaccination in cancer patients. [Table: see text]

Orthogonal Inductive Matrix Completion.

We propose orthogonal inductive matrix completion (OMIC), an interpretable approach to matrix completion based on a sum of multiple orthonormal side information terms, together with nuclear-norm regularization. The approach allows us to inject prior knowledge about the singular vectors of the ground-truth matrix. We optimize the approach by a provably converging algorithm, which optimizes all components of the model simultaneously. We study the generalization capabilities of our method in both the distribution-free setting and in the case where the sampling distribution admits uniform marginals, yielding learning guarantees that improve with the quality of the injected knowledge in both cases. As particular cases of our framework, we present models that can incorporate user and item biases or community information in a joint and additive fashion. We analyze the performance of OMIC on several synthetic and real datasets. On synthetic datasets with a sliding scale of user bias relevance, we show that OMIC better adapts to different regimes than other methods. On real-life datasets containing user/items recommendations and relevant side information, we find that OMIC surpasses the state of the art, with the added benefit of greater interpretability.