Patient COUNTS: A pilot navigation program for Asian American cancer patients.

Many Asian American cancer patients face barriers to cancer care but little is known about their navigational needs. We designed and implemented a pilot study to provide culturally- and linguistically-appropriate navigation for Asian American cancer patients. We recruited Asian American adults age 21+ years, who spoke English, Cantonese, Mandarin, or Vietnamese, with newly diagnosed, stage I-III colorectal, liver, or lung cancer in the Northern California Bay Area. Participants were assigned a language-concordant patient navigator, who provided support and resources over 6 months. Surveys were administered at baseline, 3-, and 6-months to assess sociodemographic characteristics, healthcare access, quality of life (FACT-G), and cancer care needs. Participants' mean age was 65 years (range 38-81); 62% were men, 67% spoke Chinese, and 75% reported limited English proficiency. Forty-two percent of participants had lung, 38% colorectal, and 21% liver cancer. Of 24 participants who enrolled, 67% completed the program and 75% completed standard of care cancer treatment. The average total FACT-G score was 72.6 (SD 17) at baseline, 68.0 (SD 20) at 3 months, and 69.9 (SD 22) at 6 months. All participants reported that the program was culturally appropriate and would recommend it. Asian American cancer patients in a patient navigation program reported lower quality of life compared to the general adult cancer population. Even with navigation, 75% of participants reported completing standard of care treatment. While participants were satisfied with the program, more research is needed to address the quality of cancer care Asian American cancer patients receive.

A novel approach for APT attack detection based on an advanced computing.

To enhance the effectiveness of the Advanced Persistent Threat (APT) detection process, this research proposes a new approach to build and analyze the behavior profiles of APT attacks in network traffic. To achieve this goal, this study carries out two main objectives, including (i) building the behavior profile of APT IP in network traffic using a new intelligent computation method; (ii) analyzing and evaluating the behavior profile of APT IP based on a deep graph network. Specifically, to build the behavior profile of APT IP, this article describes using a combination of two different data mining methods: Bidirectional Long Short-Term Memory (Bi) and Attention (A). Based on the obtained behavior profile, the Dynamic Graph Convolutional Neural Network (DGCNN) is proposed to extract the characteristics of APT IP and classify them. With the flexible combination of different components in the model, the important information and behavior of APT attacks are demonstrated, not only enhancing the accuracy of detecting attack campaigns but also reducing false predictions. The experimental results in the paper show that the method proposed in this study has brought better results than other approaches on all measurements. In particular, the accuracy of APT attack prediction results (Precision) reached from 84 to 91%, higher than other studies of over 7%. These experimental results have proven that the proposed BiADG model for detecting APT attacks in this study is proper and reasonable. In addition, those experimental results have not only proven the effectiveness and superiority of the proposed method in detecting APT attacks but have also opened up a new approach for other cyber-attack detections such as distributed denial of service, botnets, malware, phishing, etc.

Utilization of a natural language processing-based approach to determine the composition of artifact residues.

BACKGROUND: Determining the composition of artifact residues is a central problem in ancient residue metabolomics. This is done by comparing mass spectral features in common with an experimental artifact and an ancient artifact (standard method). While this method is simple and straightforward, we sought to increase the accuracy of predicting which plant species had been used in which artifacts. RESULTS: Here, we introduce an algorithm (new method) based on ideas from the field of natural language processing (NLP) to solve this problem. We tested our strategy on a set of modern clay pipes. To limit biases, we were not provided information on which plant species had been smoked in which clay pipes. The results indicate that our new method performed 12.5% better than the standard method in predicting the plant species smoked in each artifact. CONCLUSIONS: Utilizing an NLP-based approach, we developed a robust algorithm for characterizing the composition of artifact residues. This work also discusses other general applications in which our algorithm could be used in the field of metabolomics, such as datasets where there are a limited number of replicates.

The silent protector: Nucleoporin93's role in vascular health.

Nuclear envelope proteins have recently gained traction as novel regulators of endothelial and vascular function. Nuclear pore complexes (NPCs) stand as one of the largest protein complexes found at the nuclear envelope yet the role of component NPC proteins (i.e., nucleoporins) in vascular health remains unclear. In the issue of Aging Cell, Nguyen et al. (2024) identify Nucleoporin93, a major structural protein of the NPC, as an indispensable player in endothelial protection. This discovery raises the possibility that endothelial NPCs are susceptible to risk factors for consequent vascular disease.

Rapid Development of Primary Right Atrial Angiosarcoma.

Cardiac angiosarcomas are rare and generally followed by a high level of metastasis with poor median survival outcomes. Echocardiograms, CT scans, and MRIs are the standard methods for finding sites of cardiac tumors; however, immunohistochemical confirmation is necessary for a definitive diagnosis of angiosarcoma. A 58-year-old male presented to the emergency room with one week of dyspnea on moderate exertion accompanied by chest pain and alleviated with rest. A workup done to evaluate mass found a single 5 x 3.5 x 4.8 cm mass heavily vascularized by the right coronary artery and left circumflex involving the free wall of the right atrium with no extension to the tricuspid valve. Surgical resection was performed, and immunohistochemistry was consistent with a primary cardiac angiosarcoma. An exudative fluid analysis on pericardial and pleural fluid analysis may warrant screening for malignancy more frequently in concurrence with a patient's history and presentation. Although the time from onset of symptoms to diagnosis of cardiac angiosarcoma is not well established, further investigation of such correlation may offer insight into survival post-treatment.

Green Synthesis of Diphenyl-Substituted Alcohols Via Radical Coupling of Aromatic Alcohols Under Transition-Metal-Free Conditions.

Alcohols are common alkylating agents and starting materials alternative to harmful alkyl halides. In this study, a simple, benign and efficient pathway was developed to synthesize 1,3-diphenylpropan-1-ols via the ß-alkylation of 1-phenylethanol with benzyl alcohols. Unlike conventional borrowing hydrogen processes in which alcohols were activated by transition-metal catalyzed dehydrogenation, in this work, t-BuONa was suggested to be a dual-role reagent, namely, both base and radical initiator, for the radical coupling of aromatic alcohols. The cross-coupling reaction readily proceeded under transition metal-free conditions and an inert atmosphere, affording 1,3-diphenylpropan-1-ol with an excellent yield. A good functional group tolerance in benzyl alcohols was observed, leading to the production of various phenyl-substituted propan-1-ol derivatives in moderate-to-good yields. The mechanistic studies proposed that the reaction could involve the formation of reactive radical anions by base-mediated deprotonation and single electron transfer.

Pain management inequities by demographic and geriatric-related variables in older adult inpatients.

BACKGROUND: Pain is ubiquitous, yet understudied. The objective of this study was to analyze inequities in pain assessment and management for hospitalized older adults focusing on demographic and geriatric-related variables. METHODS: This was a retrospective cohort study from January 2013 through September 2021 of all adults 65 years or older on the general medicine service at UCSF Medical Center. Primary exposures included (1) demographic variables including race/ethnicity and limited English proficiency (LEP) status and (2) geriatric-related variables including age, dementia or mild cognitive impairment diagnosis, hearing or visual impairment, end-of-life care, and geriatrics consult involvement. Primary outcomes included (1) adjusted odds of numeric pain assessment versus other assessments and (2) adjusted opioids administered, measured by morphine milligram equivalents (MME). RESULTS: A total of 15,809 patients were included across 27,857 hospitalizations with 1,378,215 pain assessments, with a mean age of 77.8 years old. Patients were 47.4% White, 26.3% with LEP, 49.6% male, and 50.4% female. Asian (OR 0.75, 95% CI 0.70-0.80), Latinx (OR 0.90, 95% CI 0.83-0.99), and Native Hawaiian or Pacific Islander (OR 0.77, 95% CI 0.64-0.93) patients had lower odds of a numeric assessment, compared with White patients. Patients with LEP (OR 0.70, 95% CI 0.66-0.74) had lower odds of a numeric assessment, compared with English-speaking patients. Patients with dementia, hearing impairment, patients 75+, and at end-of-life were all less likely to receive a numeric assessment. Compared with White patients (86 MME, 95% CI 77-96), Asian patients (55 MME, 95% CI 46-65) received fewer opioids. Patients with LEP, dementia, hearing impairment and those 75+ years old also received significantly fewer opioids. CONCLUSION: Older, hospitalized, general medicine patients from minoritized groups and with geriatric-related conditions are uniquely vulnerable to inequitable pain assessment and management. These findings raise concerns for pain underassessment and undertreatment.

Tumor suppressive role of the antimicrobial lectin REG3A targeting the O -GlcNAc glycosylation pathway.

BACKGROUND AND AIMS: Antimicrobial proteins of the regenerating family member 3 alpha (REG3A) family provide a first line of protection against infections and transformed cells. Their expression is inducible by inflammation, which makes their role in cancer biology less clear since an immune-inflammatory context may preexist or coexist with cancer, as occurs in HCC. The aim of this study is to clarify the role of REG3A in liver carcinogenesis and to determine whether its carbohydrate-binding functions are involved. APPROACH AND RESULTS: This study provides evidence for a suppressive role of REG3A in HCC by reducing O -GlcNAcylation in 2 mouse models of HCC, in vitro cell studies, and clinical samples. REG3A expression in hepatocytes significantly reduced global O -GlcNAcylation and O -GlcNAcylation of c-MYC in preneoplastic and tumor livers and markedly inhibited HCC development in REG3A-c-MYC double transgenic mice and mice exposed to diethylnitrosamine. REG3A modified O -GlcNAcylation without altering the expression or activity of O-linked N-acetylglucosaminyltransferase, O-linked N-acetylglucosaminyl hydrolase, or glutamine fructose-6-phosphate amidotransferase. Reduced O -GlcNAcylation was consistent with decreased levels of UDP-GlcNAc in precancerous and cancerous livers. This effect was linked to the ability of REG3A to bind glucose and glucose-6 phosphate, suggested by a REG3A mutant unable to bind glucose and glucose-6 phosphate and alter O -GlcNAcylation. Importantly, patients with cirrhosis with high hepatic REG3A expression had lower levels of O -GlcNAcylation and longer cancer-free survival than REG3A-negative cirrhotic livers. CONCLUSIONS: REG3A helps fight liver cancer by reducing O -GlcNAcylation. This study suggests a new paradigm for the regulation of O -GlcNAc signaling in cancer-related pathways through interactions with the carbohydrate-binding function of REG3A.

An Inhibitory Single-Domain Antibody against Protein Z-Dependent Protease Inhibitor Promotes Thrombin Generation in Severe Hemophilia A and FXI Deficiency.

BACKGROUND: Protein Z-dependent protease inhibitor (ZPI) is an anticoagulant serpin that targets factor Xa (FXa) in the presence of protein Z (PZ), and factor XIa (FXIa). In factor-VIII-deficient mice, PZ or ZPI gene knock-out mitigates the bleeding phenotype, and pharmacological inhibition of PZ enhances thrombin generation in plasma from patients with hemophilia. AIMS: To develop a single-domain antibody (sdAb) directed against ZPI to inhibit its anticoagulant activity. METHODS: We screened for anti-ZPI sdAbs in a llama-derived phage display immune library of sdAbs. The sdAbs that bound ZPI were produced and purified for characterization. The binding of sdAbs to ZPI or other serpins was evaluated using ELISAs, and ZPI inhibition was measured in an anti-FXa or anti-FXIa chromogenic assay. The sdAbs's procoagulant activity was assessed in a thrombin generation assay in normal plasma, factor VIII- and FXI-deficient plasma. RESULTS: Of the four sdAbs found to bind to ZPI, one (referred to as ZPI-sdAb2) dose-dependently inhibited ZPI's anti-FXa and anti-FXIa activities with a mean half-maximal inhibitory concentration of 1.8 and 1.3 µM, respectively. ZPI-sdAb2 did not cross-react with other plasma serpins, such as antithrombin and α1-antitrypsin. ZPI-sdAb2 induced a significant increase in thrombin generation in plasma samples from healthy donors, patients with severe hemophilia A, and patients with FXI deficiency. CONCLUSION: ZPI-sdAb2 is the first specific, direct ZPI inhibitor found to exhibit procoagulant activity in plasma. This sdAb might have potential as a treatment for hemophilia or other bleeding disorders.

A compact co-aperture dual-sense circularly polarized antenna for simultaneous transmit and receive systems.

This paper proposes a compact design of dual-sense circularly polarized (CP) antenna for simultaneous transmit (Tx) and receive (Rx) communication systems. The primary radiating aperture of the proposed antenna is a 2 × 2 unit-cell metasurface (MS). The MS is excited by the asymmetric patch in the center, which acts as the CP source of the whole antenna structure. By properly tuning the feeding positions, dual-sense CP with high isolation can be achieved. For verification, an antenna prototype with compact dimensions of 0.36λ × 0.36λ × 0.02λ (λ is the free-space wavelength at the center operating frequency) is fabricated and measured. The measured operating bandwidth is 1.6% (2.45-2.49 GHz), in which the reflection and transmission coefficients are less than-10 dB and the axial ratio is lower than 3 dB. Within this band, the maximum isolation value is 39 dB, and the peak gain is 5.7 dBi.

Cobalt ferrite nanoparticles for annulation of C3-substituted nitroarenes and aryl isothiocyanates.

The synthesis of medicinally relevant N-aryl-substituted 2-aminobenzothiazoles often uses 2-aminothiophenol derivatives, which are not commercially abundant, as starting materials. Herein, we report a method for the annulation of C3-substituted nitroarenes and aryl isothiocyanates towards the synthesis of 2-aminobenzothiazoles. Reactions proceeded in the presence of cobalt ferrite nanoparticles as a catalyst, DABCO as a base, and DMF as a promoter. The cobalt ferrite nanoparticles could be recovered after each run and reused up to 3 times while the product yield was not diminished. Our method appears to be the first example of the direct use of substituted nitroarenes for yielding 2-aminobenzothiazoles.

An App-Based Physical Activity Intervention in Community-Dwelling Chinese-, Tagalog-, and Vietnamese-Speaking Americans: Single-Arm Intervention Study.

BACKGROUND: Physical inactivity is associated with adverse health outcomes among Asian Americans, who exhibit the least adherence to physical activity guidelines compared with other racial and ethnic groups. Mobile app-based interventions are a promising approach to promote healthy behaviors. However, there is a lack of app-based interventions focused on improving physical activity among Asian Americans whose primary language is not English. OBJECTIVE: This pilot study aimed to assess the feasibility and acceptability of a 5-week intervention using a culturally and linguistically adapted, evidence-based mobile phone app with an accelerometer program, to promote physical activity among Chinese-, Tagalog-, or Vietnamese-speaking Americans. METHODS: Participants were recruited through collaborations with community-based organizations. The intervention was adapted from a 12-month physical activity randomized controlled trial involving the app and accelerometer for English-speaking adults. Sociodemographic characteristics, lifestyle factors, and physical measurements were collected at the baseline visit. A 7-day run-in period was conducted to screen for the participants who could wear a Fitbit One (Fitbit LLC) accelerometer and complete the app's daily step diary. During the 4-week intervention period, participants wore the accelerometer and reported their daily steps in the app. Participants also received daily messages to reinforce key contents taught during an in-person educational session, remind them to input steps, and provide tailored feedback. Feasibility measures were the percentage of eligible participants completing the run-in period and the percentage of participants who used the app diary for at least 5 out of 7 days during the intervention period. We conducted poststudy participant interviews to explore overall intervention acceptability. RESULTS: A total of 19 participants were enrolled at the beginning of the study with a mean age of 47 (SD 13.3; range 29-70) years, and 58% (n=11) of them were female. Of the participants, 26% (n=5) were Chinese, 32% (n=6) were Vietnamese, and 42% (n=8) were Filipino. All participants met the run-in criteria to proceed with the intervention. Adherence to the app diary ranged from 74% (n=14) in week 2 to 95% (n=18) in week 4. The daily average steps per week from accelerometers increased each week from 8451 (SD 3378) steps during the run-in period to 10,930 (SD 4213) steps in week 4. Participants reported positive experiences including an increased motivation to walk and the enjoyment of being able to monitor their physical activity. CONCLUSIONS: This is the first pilot study of a multicomponent intervention and evidence-based mobile phone app to promote physical activity among Asian Americans who use apps in traditional Chinese, Tagalog, or Vietnamese, which demonstrated high feasibility and acceptability. Future work focused on multilingual mobile apps to address disparities in physical inactivity among Asian Americans should be considered.

Evaluation of screening algorithms to detect rectal colonization with carbapenemase-producing Enterobacterales in a resource-limited setting.

Objectives: To improve and rationalize the detection of carbapenemase-producing Enterobacterales (CPE) in rectal swabs in a high-prevalence and resource-constrained setting, addressing surveillance challenges typically encountered in laboratories with limited resources. Methods: A point prevalence survey (PPS) was conducted on 15 August 2022, in a provincial children's hospital in northern Vietnam. Rectal swab samples of all admitted children were collected and plated on a selective medium for carbapenem-resistant Enterobacterales (CRE). Species identification and antimicrobial susceptibility testing (AST) were performed by MALDI-TOF, and VITEK2 XL and interpreted according to CLSI breakpoints (2022). Carbapenemases were detected by the carbapenem inactivation method (CIM) and quantitative real-time PCR (qRT-PCR). Results: Rectal swab samples were obtained from 376 patients. Of 178 isolates growing on the CRE screening agar, 140 isolates were confirmed as Enterobacterales of which 118 (84.3%) isolates were resistant to meropenem and/or ertapenem. CIM and PCR showed that 90/118 (76.3%) were carbapenemase producers. Overall, 83/367 (22.6%) were colonized by CPE. Klebsiella pneumoniae, Escherichia coli and Enterobacter cloacae complex were the most common CPE detected, with NDM as the predominant carbapenemase (78/90; 86.7%). Phenotypic resistance to meropenem was the best predictor of CPE production (sensitivity 85.6%, specificity 100%) compared with ertapenem resistance (95.6% sensitivity, 36% specificity). CIM was 100% concordant with PCR in detecting carbapenemases. Conclusions: These findings underscore the effectiveness of meropenem resistance as a robust indicator of the production of carbapenemases and the reliability of the CIM method to detect such carbapenemases in resource-limited settings where the performance of molecular methods is not possible.

A sulfonate ligand-defected Zr-based metal-organic framework for the enhanced selective removal of anionic dyes.

In this work, we introduce a novel defective analogue of the representative 6-connected zirconium-based metal-organic framework (MOF-808), by employing 5-sulfoisophthalic acid monosodium salt (H2BTC-SO3Na) as a defect inducer via a mixed-linker approach. The structural integrity and different physicochemical properties were investigated by various characterization techniques, including powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and nitrogen physisorption at 77 K. Additionally, proton nuclear magnetic resonance (1H-NMR), energy-dispersive X-ray (EDX), and inductively coupled plasma optical emission spectroscopy (ICP-OES) were employed to confirm the presence of 6.9 mol% of the 5-sulfoisophthalate ligand within the highly crystalline MOF-808 structure. The defective material exhibited significant enhancements in the removal efficiency of various organic dyes, including approximately 64% and 77% for quinoline yellow and sunset yellow, and 56% and 13% for rhodamine B and malachite green, compared to its pristine counterpart. Importantly, the defective MOF-808 showed a remarkable selectivity toward anionic species in binary-component dyes comprising both anionic and cationic dyes.

A Comprehensive Evaluation of Dioxins and Furans Occurrence in River Sediments from a Secondary Steel Recycling Craft Village in Northern Vietnam.

This first study investigated the presence of dioxins and furans in river sediments around a craft village in Vietnam, focusing on Secondary Steel Recycling. Sediment samples were collected from various locations along the riverbed near the Da Hoi Secondary Steel Recycling village in Bac Ninh province. The analysis was conducted using a HRGC/HRMS-DFS device, detecting a total of 17 dioxin/furan isomers in all samples, with an average total concentration of 288.86 ng/kg d.w. The concentrations of dioxin/furan congeners showed minimal variation among sediment samples, ranging from 253.9 to 344.2 ng/kg d.w. The predominant compounds in the dioxin group were OCDD, while in the furan group, they were 1,2,3,4,6,7,8-HpCDF and OCDF. The chlorine content in the molecule appeared to be closely related to the concentration of dioxins and their percentage distribution. However, the levels of furan isomers did not vary significantly. The distribution of these compounds was not dependent on the flow direction, as they were mainly found in solid waste and are not water-soluble. Although the hepta and octa congeners had high concentrations, when converted to TEQ values, the tetra and penta groups (for dioxins) and the penta and hexa groups (for furans) contributed more to toxicity. Furthermore, the source of dioxins in sediments at Da Hoi does not only originate from steel recycling production activities but also from other combustion sites. The average total toxicity was 10.92 ng TEQ/kg d.w, ranging from 4.99 to 17.88 ng TEQ/kg d.w, which did not exceed the threshold specified in QCVN 43:2017/BTNMT, the National Technical Regulation on Sediment Quality. Nonetheless, these levels are still concerning. The presence of these toxic substances not only impacts aquatic organisms in the sampled water environment but also poses potential health risks to residents living nearby.

Cardiac Muscle Injury and Echocardiographic Plus Electrocardiographic Findings in Patients With 2019 Novel Coronavirus (COVID-19): A Retrospective Cohort Study.

Background: Myocardial injury has been described in coronavirus-2019 (COVID-19). Few studies have reported cardiovascular imaging data with transthoracic echocardiography (TTE) and electrocardiography (ECG) findings in COVID-19 patients, and their correlation with mortality. Methods: We conducted a retrospective cohort study that included COVID-19 patients from March 2020 through February 2021 who had TTE and ECG during hospital admission. Myocardial injury was defined by an elevated high-sensitivity troponin T level > 20 ng/L. Bivariate analysis was used to compare patients with myocardial injury and those without. Multivariate logistic regression analysis was performed to identify the variables associated with mortality. Results: A total of 438 patients were included. The mean age was 62.1 ± 14.9 years, and 58.9% were male. A total of 149 patients died, with a mortality rate of 34%. A total of 260 patients (59.4%) had myocardial injury. The average left ventricular ejection fraction was 59.8% ± 11.2%, with 30 patients (6.8%) having an ejection fraction of < 40%. Patients with myocardial injury had higher mortality than those without (P < 0.05, χ2 test). A multiple regression analysis model indicated that age, race and/or ethnicity, the development of acute respiratory distress syndrome, shock, the need for vasopressors, mechanical ventilation, and hemodialysis were the variables significantly associated with mortality. Conclusion: COVID-19 patients with myocardial injury had higher mortality than those without. Age, race and/or ethnicity, acute respiratory distress syndrome, shock, the need for vasopressors, mechanical ventilation, and hemodialysis were the clinical variables associated with mortality. The TEE and ECG variables studied were not significantly associated with mortality.

Contexte: Des atteintes myocardiques ont été décrites en présence d'une infection par le coronavirus 2019 (COVID-19). Quelques études ont rapporté des données d'imagerie cardiovasculaire obtenues par échocardiographie transthoracique (ETT) et électrocardiographie (ECG) chez des patients atteints de la COVID-19, et leur corrélation avec la mortalité. Méthodologie: Nous avons mené une étude de cohorte rétrospective comprenant des patients atteints de la COVID-19 entre mars 2020 et février 2021 qui ont été soumis à une ETT ou à une ECG pendant leur hospitalisation. L'atteinte myocardique était définie comme un taux élevé de troponine T de haute sensibilité > 20 ng/L. Une analyse à deux variables a été utilisée pour comparer les patients présentant une atteinte myocardique et ceux qui n'en présentaient pas. Une analyse de régression logistique à multiples variables a été menée pour définir les variables qui étaient associées à la mortalité. Résultats: L'étude comptait un total de 438 patients. L'âge moyen était de 62,1 ± 14,9 ans; 58,9 % étaient des hommes. Un total de 149 patients sont décédés, soit un taux de mortalité de 34 %. Un total de 260 patients (59,4 %) présentaient une atteinte myocardique. La fraction d'éjection ventriculaire gauche moyenne était de 59,8 % ± 11,2 %, alors que 30 patients (6,8 %) affichaient une fraction d'éjection inférieure à 40 %. Le taux de mortalité était plus élevé chez les patients qui présentaient une atteinte myocardique que chez ceux qui n'en présentaient pas (p < 0,05, test χ2). Selon un modèle d'analyse de régression multiple, l'âge, la race et/ou l'ethnicité, l'apparition du syndrome de détresse respiratoire aiguë, l'état de choc, le besoin de vasopresseurs, la ventilation artificielle et l'hémodialyse étaient les variables fortement liées à la mortalité. Conclusion: Parmi les patients atteints de la COVID-19, la mortalité était plus élevée chez ceux qui présentaient une atteinte myocardique que chez ceux qui n'en présentaient pas. L'âge, la race et/ou l'ethnicité, le syndrome de détresse respiratoire aiguë, l'état de choc, le besoin de vasopresseurs, la ventilation artificielle et l'hémodialyse étaient les variables cliniques liées à la mortalité. Les variables d'ETT et d'ECG étudiées n'avaient pas de lien important avec la mortalité.

Bifunctional enzyme provides absolute concentration robustness in multisite covalent modification networks.

Biochemical covalent modification networks exhibit a remarkable suite of steady state and dynamical properties such as multistationarity, oscillations, ultrasensitivity and absolute concentration robustness. This paper focuses on conditions required for a network of this type to have a species with absolute concentration robustness. We find that the robustness in a substrate is endowed by its interaction with a bifunctional enzyme, which is an enzyme that has different roles when isolated versus when bound as a substrate-enzyme complex. When isolated, the bifunctional enzyme promotes production of more molecules of the robust species while when bound, the same enzyme facilitates degradation of the robust species. These dual actions produce robustness in the large class of covalent modification networks. For each network of this type, we find the network conditions for the presence of robustness, the species that has robustness, and its robustness value. The unified approach of simultaneously analyzing a large class of networks for a single property, i.e. absolute concentration robustness, reveals the underlying mechanism of the action of bifunctional enzyme while simultaneously providing a precise mathematical description of bifunctionality.

Clinical effects of physiologic lesion testing in influencing treatment strategy for multi-vessel coronary artery disease.

Background: The application of fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) in multivessel coronary artery disease (CAD) patients has not been definitively explored. We herein assessed how treatment strategies were decided based on FFR/iFR values in vessels selected clinically. Specifically, we sought to determine whether treatment selection was based on whether the vessel tested was the clinical target stenosis. Methods: 270 consecutive patients with angiographically determined multivessel disease who underwent FFR/iFR testing were included. Patients were classified initially based on their angiographic findings, then re-evaluated from FFR/iFR results (normal or abnormal). Tested lesions were classified into target or non-target lesions based on clinical and non-invasive evaluations. Results: Abnormal FFR/iFR values were demonstrated in 51.9 % of patients, in whom 51.4 % received coronary stenting (PCI) and 44.3 % had bypass surgery (CABG). With two-vessel CAD patients, medical therapy was preferred when the target lesion was normal (72.6 %), while PCI was preferred when it was abnormal (78.4 %). In non-target lesions, PCI was preferred regardless of FFR/iFR results (78.0 %). With three-vessel CAD patients, CABG was preferred when the target lesion was abnormal (68.5 %), and there was no difference in the selected modality when it was normal. Furthermore, the incidence of tested lesions was higher in the left anterior descending (LAD) compared to other coronary arteries, and two-vessel CAD patients with LAD stenoses were more frequently treated by PCI. Conclusion: The use of invasive physiologic testing in multivessel CAD patients may alter the preferred treatment strategy, leading to an overall increase in PCI selection.

Convergence of coronary artery disease genes onto endothelial cell programs.

Linking variants from genome-wide association studies (GWAS) to underlying mechanisms of disease remains a challenge1-3. For some diseases, a successful strategy has been to look for cases in which multiple GWAS loci contain genes that act in the same biological pathway1-6. However, our knowledge of which genes act in which pathways is incomplete, particularly for cell-type-specific pathways or understudied genes. Here we introduce a method to connect GWAS variants to functions. This method links variants to genes using epigenomics data, links genes to pathways de novo using Perturb-seq and integrates these data to identify convergence of GWAS loci onto pathways. We apply this approach to study the role of endothelial cells in genetic risk for coronary artery disease (CAD), and discover 43 CAD GWAS signals that converge on the cerebral cavernous malformation (CCM) signalling pathway. Two regulators of this pathway, CCM2 and TLNRD1, are each linked to a CAD risk variant, regulate other CAD risk genes and affect atheroprotective processes in endothelial cells. These results suggest a model whereby CAD risk is driven in part by the convergence of causal genes onto a particular transcriptional pathway in endothelial cells. They highlight shared genes between common and rare vascular diseases (CAD and CCM), and identify TLNRD1 as a new, previously uncharacterized member of the CCM signalling pathway. This approach will be widely useful for linking variants to functions for other common polygenic diseases.

Virtual BUILD Research Collaboratory: A biomedical data science training using innovative pedagogy to address structures of racism and inequitable stress for undergraduates of color.

OBJECTIVE: The unprecedented events of 2020 required a pivot in scientific training to better prepare the biomedical research workforce to address global pandemics, structural racism, and social inequities that devastate human health individually and erode it collectively. Furthermore, this pivot had to be accomplished in the virtual environment given the nation-wide lockdown. METHODS: These needs and context led to leveraging of the San Francisco Building Infrastructure Leading to Diversity (SF BUILD) theories of change to innovate a Virtual BUILD Research Collaboratory (VBRC). The purpose of VBRC was to train Black, Indigenous, and people of color (BIPOC) students to apply their unique perspectives to biomedical research. These training activities were evaluated using a pre-post survey design that included both validated and new psychosocial scales. A new scale was piloted to measure culturally relevant pedagogy. RESULTS: VBRC scholars increased science identity on two items: thinking of myself as a scientist (+1point, p = 0.006) and belonging to a community of scientists (+1point, p = 0.069). Overall, scholars perceived stress also decreased over VBRC (-2.35 points, p = 0.02). Post VBRC, scholars had high agency scores (µ = 11.02, Md = 12, range = 6-12, σ = 1.62) and cultural humility scores (µ = 22.11, Md = 23, range = 12-24, σ = 2.71). No notable race/ethnic differences were found in any measures. CONCLUSIONS: Taken together, our innovative approach to data science training for BIPOC in unprecedented times shows promise for better preparing the workforce critically needed to address the fundamental gaps in knowledge at the intersection of public health, structural racism, and biomedical sciences.