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A method to generate crop calendar and phenology-related maps at a parcel level of four major irrigated crops (rice, maize, sunflower and tomato) is shown. The method combines images from the ASTER and MODIS sensors in an object-based image analysis framework, as well as testing of three different fitting curves by using the TIMESAT software. Averaged estimation of calendar dates were 85%, from 92% in the estimation of emergence and harvest dates in rice to 69% in the case of harvest date in tomato.

The strategic management of agricultural lands involves crop field monitoring each year. Crop discrimination via remote sensing is a complex task, especially if different crops have a similar spectral response and cropping pattern. In such cases, crop identification could be improved by combining object-based image analysis and advanced machine learning methods. In this investigation, we evaluated the C4.5 decision tree, logistic regression (LR), support vector machine (SVM) and multilayer perceptron (MLP) neural network methods, both as single classifiers and combined in a hierarchical classification, for the mapping of nine major summer crops (both woody and herbaceous) from ASTER satellite images captured in two different dates. Each method was built with different combinations of spectral and textural features obtained after the segmentation of the remote images in an object-based framework. As single classifiers, MLP and SVM obtained maximum overall accuracy of 88%, slightly higher than LR (86%) and notably higher than C4.5 (79%). The SVM+SVM classifier (best method) improved these results to 89%. In most cases, the hierarchical classifiers considerably increased the accuracy of the most poorly classified class (minimum sensitivity). The SVM+SVM method offered a significant improvement in classification accuracy for all of the studied crops compared to the conventional decision tree classifier, ranging between 4% for safflower and 29% for corn, which suggests the application of object-based image analysis and advanced machine learning methods in complex crop classification tasks.

Objective: To assess the clinical characteristics and the factors that influenced the prognosis of patients with HIV and infection caused by Rhodococcus equi.Design: Observational, multicenter study in 29 Spanish general hospitals.Setting: These hospitals comprised a total of 20,250 beds for acute patients and served a population of 9,716,880 inhabitants.Patients: All patients with HIV and diagnosed R equi infection until September 1998.Results: During the study period, 19,374 cases of AIDS were diagnosed. Sixty-seven patients were included (55 male patients; mean +/- SD age, 31.7 +/- 5.8 years). At the time of diagnosis of R equi infection, the mean CD4+ lymphocyte count was 35/ micro L (range, 1 to 183/ micro L) and the stage of HIV infection was A3 in 10.4% of patients, B3 in 31.3%, C3 in 56.7%, and unknown in 1.5%. R equi was most commonly isolated in sputum (52.2%), blood cultures (50.7%), and samples from bronchoscopy (31.3%). Chest radiographic findings were abnormal in 65 patients (97%). Infiltrates were observed in all of them, with cavitations in 45 patients. The most active antibiotics against the strains isolated were vancomycin, amikacin, rifampicin, imipenem, ciprofloxacin, and erythromycin. After a mean follow-up of 10.7 +/- 12.8 months, 23 patients (34.3%) died due to causes related to R equi infection and 6 other patients showed evidence of progression of the infection. The absence of highly active antiretroviral therapy (HAART) was independently associated with mortality related to R equi infection (relative risk, 53.4; 95% confidence interval, 1.7 to 1,699). Survival of patients treated with HAART was much higher than that of patients who did not receive this therapy.Conclusions: Infection by R equi is an infrequent, opportunistic complication of HIV infection and occurs during advanced stages of immunodepression. In these patients, it leads to a severe illness that usually causes a bacteremic, cavitary pneumonia, although HAART can improve the prognosis. [ABSTRACT FROM AUTHOR]

Background: A comprehensive mechanistic assessment of normothermic machine perfusion (NMP) is an essential step toward identifying biomarkers to assess liver viability. Although some studies have evaluated the effect of NMP on inflammation markers, there are other key pathological mechanisms involved in ischemia/reperfusion injury (IRI) that have not yet been evaluated., Methods: Eight human donor livers preserved by NMP were included to analyze IRI during preservation. Concentrations of several biomarkers involved in different biological processes of IRI were measured in the perfusate., Results: Perfusate levels of intercellular adhesion molecule 1, P-selectin, vascular cell adhesion molecule 1, metalloproteinase with thrombospondin motif type 1, member 13, phospholipase A2 group VII, and syndecan-1 progressively increased during NMP. Noteworthy, perfusate lactate levels showed a strong correlation with C-X-C motif chemokine ligand 10 ( P  = 0.001), intercellular adhesion molecule 1 ( P  = 0.01), and urokinase plasminogen activator ( P  = 0.001)., Conclusions: Perfusate lactate correlates with the main underlying biological mechanisms occurring in the NMP environment. Moreover, several IRI biomarkers accumulate during NMP, which may limit the extent of the benefits of this technology., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

This National Lipid Association (NLA) Expert Clinical Consensus provides an overview of the physiologic and clinical considerations regarding the role of apolipoprotein B (apoB) measurement to guide clinical care based on the available scientific evidence and expert opinion. ApoB represents the total concentration of atherogenic lipoprotein particles in the circulation and more accurately reflects the atherogenic burden of lipoproteins when compared to low-density lipoprotein cholesterol (LDL-C). ApoB is a validated clinical measurement that augments the information found in a standard lipoprotein lipid panel; therefore, there is clinical value in using apoB in conjunction with a standard lipoprotein lipid profile when assessing risk and managing lipid-lowering therapy (LLT). ApoB has been shown to be superior to LDL-C in risk assessment both before and during treatment with LLT. In individuals, there can be discordance between levels of LDL-C and apoB, as well as LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C), despite high levels of population-wide correlation. When there is discordance between LDL-C and apoB, or LDL-C and non-HDL-C, atherosclerotic cardiovascular disease risk generally aligns better with apoB or non-HDL-C. Additionally, apoB can be used in tandem with standard lipoprotein lipid measurements to diagnose distinct lipoprotein phenotypes. ApoB testing can inform clinical prognosis and care, as well as enable family cascade screening, when an inherited lipoprotein syndrome is identified. The NLA and other organizations will continue to educate clinicians about the role of apoB measurement in improving clinical risk assessment and dyslipidemia management. An urgent need exists to improve access and reimbursement for apoB testing., (Copyright © 2024. Published by Elsevier Inc.)

Cellular mRNA levels, particularly under stress conditions, can be finely regulated by the coordinated action of transcription and degradation processes. Elements of the 5'-3' mRNA degradation pathway, functionally associated with the exonuclease Xrn1, can bind to nuclear chromatin and modulate gene transcription. Within this group are the so-called decapping activators, including Pat1, Dhh1, and Lsm1. In this work, we have investigated the role of Pat1 in the yeast adaptive transcriptional response to cell wall stress. Thus, we demonstrated that in the absence of Pat1, the transcriptional induction of genes regulated by the Cell Wall Integrity MAPK pathway was significantly affected, with no effect on the stability of these transcripts. Furthermore, under cell wall stress conditions, Pat1 is recruited to Cell Wall Integrity-responsive genes in parallel with the RNA Pol II complex, participating both in pre-initiation complex assembly and transcriptional elongation. Indeed, strains lacking Pat1 showed lower recruitment of the transcription factor Rlm1, less histone H3 displacement at Cell Wall Integrity gene promoters, and impaired recruitment and progression of RNA Pol II. Moreover, Pat1 and the MAPK Slt2 occupied the coding regions interdependently. Our results support the idea that Pat1 and presumably other decay factors behave as transcriptional regulators of Cell Wall Integrity-responsive genes under cell wall stress conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Breast arterial calcifications (BAC) are incidentally observed on mammograms, yet their implications remain unclear. We investigated lifestyle, reproductive, and cardiovascular determinants of BAC in women undergoing mammography screening. Further, we investigated the relationship between BAC, coronary arterial calcifications (CAC) and estimated 10-year atherosclerotic cardiovascular (ASCVD) risk., Methods: In this cross-sectional study, we obtained reproductive history and CVD risk factors from 215 women aged 18 or older who underwent mammography and cardiac computed tomographic angiography (CCTA) within a 2-year period between 2007 and 2017 at hospital. BAC was categorized as binary (present/absent) and semi-quantitatively (mild, moderate, severe). CAC was determined using the Agatston method and recorded as binary (present/absent). Adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated, accounting for age as a confounding factor. ASCVD risk over a 10-year period was calculated using the Pooled Cohort Risk Equations., Results: Older age, systolic and diastolic blood pressures, higher parity, and younger age at first birth (≤28 years) were significantly associated with greater odds of BAC. Women with both BAC and CAC had the highest estimated 10-year risk of ASCVD (13.30 %). Those with only BAC (8.80 %), only CAC (5.80 %), and no BAC or CAC (4.40 %) had lower estimated 10-year risks of ASCVD. No association was detected between presence of BAC and CAC., Conclusions: These findings support the hypothesis that BAC on a screening mammogram may help to identify women at potentially increased risk of future cardiovascular disease without additional cost and radiation exposure., Competing Interests: Declaration of competing interest No potential conflicts of interest were disclosed. Authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Our goal was to assess the coagulation profile in the immediate postoperative time after major liver surgery and its association with the liver function. Our hypothesis is that a decreased synthesis of the coagulation factor levels reflects an impaired liver synthesis following hepatic resection and will be associated with poor outcomes. This is a prospective, observational study recruiting consecutive patients scheduled for major liver resection in a tertiary hospital. Coagulation profile was assessed by conventional assays, viscoelastic assays and coagulation factor levels preoperatively and, on postoperative days 1, 2 and 6. Factor VIII to protein C (FVIII/PC) ratio has been used as a surrogate marker of hemostatic imbalance. Liver function was measured with conventional and indocyanine green (ICG) clearance tests, which were obtained preoperatively and on postoperative days 1 and 2. Sixty patients were recruited and 51 were included in the study. There is a clear increase in FVIII/PC ratio after surgery, which was significantly associated with low liver function, being more pronounced beyond postoperative day 2 and in patients with poorer liver function ( P  < 0.001). High FVIII/PC ratio values were significantly associated with higher postoperative morbidity, prolonged ICU and hospital stay and less survival ( P  < 0.05). High FVIII/PC ratio on postoperative day 2 was found to be predictor of posthepatectomy liver failure (PHLF; area under the ROC curve = 0.8129). Early postoperative high FVIII/PC ratio values are associated with low liver function, PHLF and poorer outcomes in patients undergoing major hepatic resection., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

More than 10 million Europeans show signs of mild cognitive impairment (MCI), a transitional stage between normal brain aging and dementia stage memory disorder. The path MCI takes can be divergent; while some maintain stability or even revert to cognitive norms, alarmingly, up to half of the cases progress to dementia within 5 years. Current diagnostic practice lacks the necessary screening tools to identify those at risk of progression. The European patient experience often involves a long journey from the initial signs of MCI to the eventual diagnosis of dementia. The trajectory is far from ideal. Here, we introduce the AI-Mind project, a pioneering initiative with an innovative approach to early risk assessment through the implementation of advanced artificial intelligence (AI) on multimodal data. The cutting-edge AI-based tools developed in the project aim not only to accelerate the diagnostic process but also to deliver highly accurate predictions regarding an individual's risk of developing dementia when prevention and intervention may still be possible. AI-Mind is a European Research and Innovation Action (RIA H2020-SC1-BHC-06-2020, No. 964220) financed between 2021 and 2026. First, the AI-Mind Connector identifies dysfunctional brain networks based on high-density magneto- and electroencephalography (M/EEG) recordings. Second, the AI-Mind Predictor predicts dementia risk using data from the Connector , enriched with computerized cognitive tests, genetic and protein biomarkers, as well as sociodemographic and clinical variables. AI-Mind is integrated within a network of major European initiatives, including The Virtual Brain, The Virtual Epileptic Patient, and EBRAINS AISBL service for sensitive data, HealthDataCloud, where big patient data are generated for advancing digital and virtual twin technology development. AI-Mind's innovation lies not only in its early prediction of dementia risk, but it also enables a virtual laboratory scenario for hypothesis-driven personalized intervention research. This article introduces the background of the AI-Mind project and its clinical study protocol, setting the stage for future scientific contributions., Competing Interests: CH-H was employed by BrainSymph AS. VAy, JP, and LP were employed by Lurtis Rules S.L. EC was employed by Pre Diagnostics AS. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Haraldsen, Hatlestad-Hall, Marra, Renvall, Maestú, Acosta-Hernández, Alfonsin, Andersson, Anand, Ayllón, Babic, Belhadi, Birck, Bruña, Caraglia, Carrarini, Christensen, Cicchetti, Daugbjerg, Di Bidino, Diaz-Ponce, Drews, Giuffrè, Georges, Gil-Gregorio, Gove, Govers, Hallock, Hietanen, Holmen, Hotta, Kaski, Khadka, Kinnunen, Koivisto, Kulashekhar, Larsen, Liljeström, Lind, Marcos Dolado, Marshall, Merz, Miraglia, Montonen, Mäntynen, Øksengård, Olazarán, Paajanen, Peña, Peña, Peniche, Perez, Radwan, Ramírez-Toraño, Rodríguez-Pedrero, Saarinen, Salas-Carrillo, Salmelin, Sousa, Suyuthi, Toft, Toharia, Tveitstøl, Tveter, Upreti, Vermeulen, Vecchio, Yazidi and Rossini.)

Background: Rates of cannabis use are increasing in the United States, likely as a result of changes in societal attitudes and expanding legalization. Although many patients report wanting to discuss the risks and benefits of cannabis use with their clinical providers, many providers hold conflicting beliefs regarding cannabis use and often do not engage patients in discussion about cannabis. This dilemma is underscored by the limitations imposed on cannabis related research, and lack of empirically based best-practice guidelines for clinicians when addressing cannabis use with patients., Objectives: We aimed to briefly summarize clinician and patient attitudes toward cannabis use and review current clinical guidelines and provide suggestions to assist health care providers and clinicians in increasing their comfort and skill in discussing cannabis use with patients., Methods: A narrative review on attitudes toward cannabis use and clinical guidelines was performed to summarize the literature and provide evidence-based recommendations., Results: Attitudes toward cannabis use have been shaped by personal and political factors and contribute to clinician hesitance in speaking with patients about the topic. Administrative barriers have hindered the development of clearer public health guidelines that might enable the dissemination of evidence-based information on the health effects of cannabis use and might ultimately lead to better health outcomes., Conclusion: Not discussing cannabis use with patients may be a crucial missed opportunity for harm reduction. In the absence of empirically supported best-practice guidelines, a person-centered approach can facilitate conversations on the harms and benefits of cannabis use., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The objective of this scientific statement is to evaluate contemporary evidence that either supports or refutes the conclusion that aggressive low-density lipoprotein cholesterol lowering or lipid lowering exerts toxic effects on the brain, leading to cognitive impairment or dementia or hemorrhagic stroke. The writing group used literature reviews, references to published clinical and epidemiology studies, clinical and public health guidelines, authoritative statements, and expert opinion to summarize existing evidence and to identify gaps in current knowledge. Although some retrospective, case control, and prospective longitudinal studies suggest that statins and low-density lipoprotein cholesterol lowering are associated with cognitive impairment or dementia, the preponderance of observational studies and data from randomized trials do not support this conclusion. The risk of a hemorrhagic stroke associated with statin therapy in patients without a history of cerebrovascular disease is nonsignificant, and achieving very low levels of low-density lipoprotein cholesterol does not increase that risk. Data reflecting the risk of hemorrhagic stroke with lipid-lowering treatment among patients with a history of hemorrhagic stroke are not robust and require additional focused study.

Background: Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death in the United States. Case-based learning using electronic delivery of the modules can educate clinicians and improve translation of evidence-based guidelines into practice for high-risk ASCVD patients., Objective: To develop and optimize module design, content, and usability of e-learning modules to teach clinicians evidence-based management in accordance with multi-society guidelines for high-risk ASCVD patients that will be implemented and evaluated in U.S. health systems in the TEACH-ASCVD study., Methods: Seven e-learning modules were created by a committee of lipid experts. Focus groups were conducted with lipid experts to elicit feedback on case content followed by interviews with a target audience of clinicians to assess usability of the online module platform. Responses from both groups were evaluated, and appropriate changes were made to improve the e-learning modules. Design of the TEACH-ASCVD study is presented., Results: Feedback regarding case content by lipid experts included providing more detailed patient histories, clarifying various diagnostic criteria, and emphasizing clinical best practices based on evidence-based guidelines. The target audience clinician group reported an agreeable experience with the e-learning modules but noted a discordance between the evidence-based guidelines and clinical decision-making in their own practices. Participants felt the modules would help educate clinicians in managing high-risk ASCVD patients., Conclusion: Clinicians must be informed of best practices as the field of lipidology continues to evolve. E-learning modules provide a concise, valuable, and accessible mechanism for educating clinicians regarding changes in the field to deliver the best patient care., (Copyright © 2023 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Most of the currently available cytotoxic agents for tackling cancer are devoid of selectivity, thus causing severe side-effects. This situation stimulated us to develop new antiproliferative agents with enhanced affinity towards tumour cells. We focused our attention on novel chalcogen-containing compounds (thiosemicarbazones, disulfides, selenoureas, thio- and selenocyanates), and particularly on selenium derivatives, as it has been documented that this kind of compounds might act as prodrugs releasing selenium-based reactive species on tumour cells. Particularly interesting in terms of potency and selectivity was a pharmacophore comprised by a selenocyanato-alkyl fragment connected to a p-phenylenediamine residue, where the nature of the second amino moiety (free, Boc-protected, enamine-protected) provided a wide variety of antiproliferative activities, ranging from the low micromolar to the nanomolar values. The optimized structure was in turn conjugated through a peptide linkage with biotin (vitamin B 7 ), a cellular growth promoter, whose receptor is overexpressed in numerous cancer cells; the purpose was to develop a selective vector towards malignant cells. Such biotinylated derivative behaved as a very strong antiproliferative agent, achieving GI 50 values in the low nM range for most of the tested cancer cells; moreover, it was featured with an outstanding selectivity, with GI 50  > 100 µM against human fibroblasts. Mechanistic studies on the mode of inhibition of the biotinylated selenocyanate revealed (Annexin-V assay) a remarkable increase in the number of apoptotic cells compared to the control experiment; moreover, depolarization of the mitochondrial membrane was detected by flow cytometry analysis, and with fluorescent microscopy, what supports the apoptotic cell death. Prior to the apoptotic events, cytostatic effects were observed against SW1573 cells using label-free cell-living imaging; therefore, tumour cell division was prevented. Multidrug resistant cell lines exhibited a reduced sensitivity towards the biotinylated selenocyanate, probably due to its P-gp-mediated efflux. Remarkably, antiproliferative levels could be restored by co-administration with tariquidar, a P-gp inhibitor; this approach can, therefore, overcome multidrug resistance mediated by the P-gp efflux system., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Latino, Black, American Indian/Alaska Native (AI/AN), and Native Hawaiian or Other Pacific Islander people have the highest hospitalizations and death rates from COVID-19. Social inequalities have exacerbated COVID-19 related health disparities. This study examines social and structural determinants of COVID-19 vaccine uptake. Results from logistic regressions suggest Latino and Black people were less likely to be vaccinated. People that did not have health insurance, a primary care doctor and were unemployed were more than 30% less likely to be vaccinated for COVID-19. Greater perceived health inequalities in one's neighborhood and perceived racial/ethnic discrimination were associated with a decreased odds in being vaccinated. People that suffered the loss of a household member from COVID-19 were three times more likely to have been vaccinated. Establishing policies that will increase access to health insurance and create jobs with living wages may have lasting impacts. Furthermore, collaboration with local and national community organizations can enhance the development of sustainable solutions., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Crop protection is a key activity for the sustainability and feasibility of agriculture in a current context of climate change, which is causing the destabilization of agricultural practices and an increase in the incidence of current or invasive pests, and a growing world population that requires guaranteeing the food supply chain and ensuring food security. In view of these events, this article provides a contextual review in six sections on the role of artificial intelligence (AI), machine learning (ML) and other emerging technologies to solve current and future challenges of crop protection. Over time, crop protection has progressed from a primitive agriculture 1.0 (Ag1.0) through various technological developments to reach a level of maturity closelyin line with Ag5.0 (section 1), which is characterized by successfully leveraging ML capacity and modern agricultural devices and machines that perceive, analyze and actuate following the main stages of precision crop protection (section 2). Section 3 presents a taxonomy of ML algorithms that support the development and implementation of precision crop protection, while section 4 analyses the scientific impact of ML on the basis of an extensive bibliometric study of >120 algorithms, outlining the most widely used ML and deep learning (DL) techniques currently applied in relevant case studies on the detection and control of crop diseases, weeds and plagues. Section 5 describes 39 emerging technologies in the fields of smart sensors and other advanced hardware devices, telecommunications, proximal and remote sensing, and AI-based robotics that will foreseeably lead the next generation of perception-based, decision-making and actuation systems for digitized, smart and real-time crop protection in a realistic Ag5.0. Finally, section 6 highlights the main conclusions and final remarks., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mesías-Ruiz, Pérez-Ortiz, Dorado, de Castro and Peña.)

High intra-abdominal pressure (IAP) during laparoscopic surgery is associated with reduced splanchnic blood flow. It is uncertain whether a low IAP prevents this reduction. We assessed the effect of an individualized low-pneumoperitoneum-pressure strategy on liver perfusion. This was a single-center substudy of the multicenter 'Individualized Pneumoperitoneum Pressure in Colorectal Laparoscopic Surgery versus Standard Therapy II study' (IPPCollapse-II), a randomized clinical trial in which patients received an individualized low-pneumoperitoneum strategy (IPP) or a standard pneumoperitoneum strategy (SPP). Liver perfusion was indirectly assessed by the indocyanine green plasma disappearance rate (ICG-PDR) and the secondary endpoint was ICG retention rate after 15 min (R 15 ) using pulse spectrophotometry. Multivariable beta regression was used to assess the association between group assignment and ICG-PDR and ICG-R 15 . All 29 patients from the participating center were included. Median IAP was 8 (25th-75th percentile: 8-10) versus 12 (12,12) mmHg, in IPP and SPP patients, respectively ( p < 0.001). ICG-PDR was higher (OR 1.42, 95%-CI 1.10-1.82; p = 0.006) and PDR-R 15 was lower in IPP patients compared with SPP patients (OR 0.46, 95%-CI 0.29-0.73; p = 0.001). During laparoscopic colorectal surgery, an individualized low pneumoperitoneum may prevent a reduction in liver perfusion.

The need for total knee arthroplasty is increasing considerably and one of the goals is to achieve post-surgical coronal alignment. Robotic surgical assistance achieves a functional alignment, which is a hip-knee-ankle angle of 0°. However, it is not possible to provide robotic assisted surgery to all our patients so we must include the full-length hip-to-ankle AP weight-bearing radiograph in preoperative planning to obtain a "safe zone" alignment, which is a post-surgical hip-knee-ankle Angle of 0 ± 3°. How can we achieve a "safe zone" alignment total knee arthroplasty in patients with extra-articular deformity?

Background: Prognostic significance of non-obstructive left main (LM) disease was recently reported. However, the influence of diabetes mellitus (DM) on event rates in patients with and without non-obstructive LM disease is not well-known., Methods: We evaluated 27,252 patients undergoing coronary computed tomographic angiography from the COroNary CT Angiography Evaluation For Clinical Outcomes: An InteRnational Multicenter (CONFIRM) Registry. Cumulative long-term incidence of all-cause mortality (ACM) was assessed between DM and non-DM patients by normal or non-obstructive LM disease (1-49% stenosis)., Results: The mean age of the study population was 57.6±12.6 years. Of the 27,252 patients, 4,434 (16%) patients had DM. A total of 899 (3%) deaths occurred during the follow-up of 3.6±1.9. years. Compared to patients with normal LM, those with non-obstructive LM had more pronounced overall coronary atherosclerosis and more cardiovascular risk factors. After clinical risk factors, segment involvement score, and stenosis severity adjustment, compared to patients without DM and normal LM, patients with DM were associated with increased ACM regardless of normal (HR 1.48, 95% CI 1.22-1.78, p<0.001) or non-obstructive LM (HR 1.46, 95% CI 1.04-2.04, p=0.029), while nonobstructive LM disease was not associated with increased ACM in patients without DM (HR 0.85, 95% CI 0.67-1.07, p=0.165) and there was no significant interaction between DM and LM status (HR 1.03, 95% CI 0.69-1.54, p=0.879)., Conclusion: From the CONFIRM registry, we demonstrated that DM was associated with increased ACM. However, the presence of non-obstructive LM was not an independent risk marker of ACM, and there was no significant interaction between DM and non-obstructive LM disease for ACM., (Copyright © 2022 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

The percentage of older people is increasing worldwide. Loneliness and anxious−depressive states are emerging health conditions in this population group, and these conditions give rise to higher morbidity and mortality. Physical activity (PA) and social relationships have been linked to physical and mental health. The objective of this study was to evaluate whether a 4-month programme of moderate PA in a group would improve the emotional state, levels of social support, and quality of life in a sample of individuals >64 years of age. A multicentre randomised clinical trial was designed in primary care. Ninety (90) participants were selected. After the intervention, there were positive differences between the groups, with significant improvements in the intervention group (IG) in depression, anxiety, health status perception, and social support. Walking in a group two days per week for 4 months reduced clinical depression and anxiety by 59% and 45%, respectively. The level of satisfaction was very high, and adherence was high. In conclusion, the moderate group PA programme improved clinical anxiety, depression, social support, and perceptions of health status in the patients studied., Competing Interests: The authors declare no conflicts of interest.

Background: Determination of indocyanine green (ICG) plasma disappearance rate (PDR) is a simple, inexpensive, and noninvasive tool to assess liver perfusion, absorption, and elimination. Its application in the liver transplant process has not been widely incorporated in clinical practice. This study aims to assess the usefulness of ICG PDR in the donor selection setting and in the early post-transplant phase and to analyze its variation between these 2 time points., Methods: We performed a single-center prospective observational study. ICG clearance test was performed in 50 brain-dead donors (T0-PDR) to assess concordance with graft suitability. Rejected grafts biopsy specimens were analyzed to correlate histology with T0-PDR. In the recipients, ICG PDR was performed before wound closure (T1-PDR). The association of T0, T1, and T0-T1 variation with the development of early allograft dysfunction (EAD) was investigated., Results: A total of 23 of 50 grafts were discarded because of poor macroscopic quality. A T0-PDR below 15.5%/min could predict graft rejection with 100% specificity and 69.6% sensitivity. All the biopsy specimens from donors with PDR < 10 %/min showed liver fibrosis. A total of 25 of the remaining 27 grafts were implanted; 5 patients (20%) developed EAD. T1-PDR performed better than T0-T1 variation to predict dysfunction., Conclusions: ICG PDR could be used in the donors as a filter to discard poor-quality grafts before procurement and, in the early post-transplant phase, to predict EAD., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Weed management involving tillage and/or herbicides has generally led to a decline of plant diversity in agroecosystems, with negative impacts on ecosystem services provision. The use of plant covers has become the predominant alternative in vineyard management, with numerous studies focusing on analyzing the advantages and disadvantages of plant covers compared to the aforementioned management. Although the impacts of weed management on taxonomic diversity have been widely studied, many gaps remain on their effects on plant functional diversity. As plant functional diversity is linked to the delivery of key ecosystem services in agroecosystems, understanding these effects could enable the development of more sustainable practices. From 2008 to 2018, a long-term trial was carried out in a Mediterranean vineyard to assess different agricultural practices. In this article, we examined how weed management, as well as irrigation use, could affect plant functional diversity. Based on 10 functional traits, such as plant height, specific leaf area or seed mass, we measured different indices of functional diversity and used null models to detect processes of trait convergence and divergence. Our results revealed that weed management and irrigation use had a significant effect on plant functional diversity. Mown plots showed the highest functional richness but were functionally convergent, since mowing was a strong functional filter on most of the traits. Tillage also behaved as a functional filter on some vegetative traits, but favored the divergence of certain reproductive traits. Herbicide-treated and irrigated plots showed the highest values of functional divergence by promoting more competitive species with more divergent trait values. The effect of weed management on these community assembly processes was shaped by the use of irrigation in vineyard rows, leading to functional divergence in those vegetative traits related to resource acquisition and seed mass. These results suggest that greater functional diversity may be associated with the bias caused by higher occurrence of competitive species (e.g. Convolvulus arvensis , Sonchus asper ) with contrasting values for certain traits. Therefore, since these species are considered harmful to crops, higher plant functional diversity might not be a desirable indicator in agroecosystems., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Guerra, Cabello, Fernández-Quintanilla, Peña and Dorado.)

During June 2022, Spain was one of the countries most affected worldwide by a multicountry monkeypox outbreak with chains of transmission without identified links to disease-endemic countries. We provide epidemiologic features of cases reported in Spain and the coordinated measures taken to respond to this outbreak.

This article assesses the use of under-vine living mulches in Mediterranean vineyards characterized by limited water resources, one of the reasons why this agronomic practice is currently unusual in these environments. The aim of the study was to test whether the use of this alternative method in Mediterranean vineyards could suppress noxious weeds without hindering optimal vineyard development. For this purpose, four native species were selected as living mulches: Festuca ovina , Pilosella officinarum , Plantago coronopus , and Plantago lanceolata . The variables measured during three years in two different experimental farms were: (a) living mulch cover, as a possible predictor of weed suppression success; (b) weed density and weed biomass, with special attention to noxious weed species; and (c) pruning weights, measured in the last year to analyze the cumulative effect of the treatments on the grapevine vegetative growth. Our results revealed that living mulches with high cover rates (average over 70%) also showed weed suppression of up to 95%, significantly controlling the occurrence of noxious weeds such as Erigeron canadensis . No significant effect of the different treatments on vine vegetative growth was found, although further studies would be necessary. Based on these findings, it can be concluded that under-vine living mulches could be an efficient and environmentally friendly method for weed control in Mediterranean vineyards where irrigation is available.

Conditions altering the yeast cell wall lead to the activation of an adaptive transcriptional response mainly governed by the cell wall integrity (CWI) mitogen-activated protein kinase (MAPK) pathway. Two high-throughput screenings were developed using the yTHC collection of yeast conditional mutant strains to systematically identify essential genes related to cell wall integrity, and those required for the transcriptional program elicited by cell wall stress. Depleted expression of 52 essential genes resulted in hypersensitivity to the dye Calcofluor white, with chromatin organization, Golgi vesicle transport, rRNA processing, and protein glycosylation processes, as the most highly representative functional groups. Via a flow cytometry-based quantitative assay using a CWI reporter plasmid, 97 strains exhibiting reduced gene-reporter expression levels upon stress were uncovered, highlighting genes associated with RNA metabolism, transcription/translation, protein degradation, and chromatin organization. This screening also led to the discovery of 41 strains displaying a basal increase in CWI-associated gene expression, including mainly putative cell wall-related genes. Interestingly, several members of the RSC chromatin remodelling complex were uncovered in both screenings. Notably, Rsc9 was necessary to regulate the gene expression of CWI-related genes both under stress and non-stress conditions, suggesting distinct requirements of the RSC complex for remodelling particular genes.

Living cells exposed to stressful environmental situations can elicit cellular responses that guarantee maximal cell survival. Most of these responses are mediated by mitogen-activated protein kinase (MAPK) cascades, which are highly conserved from yeast to humans. Cell wall damage conditions in the yeast Saccharomyces cerevisiae elicit rescue mechanisms mainly associated with reprogramming specific transcriptional responses via the cell wall integrity (CWI) pathway. Regulation of gene expression by this pathway is coordinated by the MAPK Slt2/Mpk1, mainly via Rlm1 and, to a lesser extent, through SBF (Swi4/Swi6) transcription factors. In this review, we summarize the molecular mechanisms controlling gene expression upon cell wall stress and the role of chromatin structure in these processes. Some of these mechanisms are also discussed in the context of other stresses governed by different yeast MAPK pathways. Slt2 regulates both transcriptional initiation and elongation by interacting with chromatin at the promoter and coding regions of CWI-responsive genes but using different mechanisms for Rlm1- and SBF-dependent genes. Since MAPK pathways are very well conserved in eukaryotic cells and are essential for controlling cellular physiology, improving our knowledge regarding how they regulate gene expression could impact the future identification of novel targets for therapeutic intervention.

This paper assessed the effectiveness of Respondent Driven Sampling (RDS) in recruiting undocumented Latinx immigrants for a prevalence health study at a time of heightened immigration enforcement. RDS was used to collect and analyze data from clinical interviews with 254 undocumented Latinx immigrant adults, enabling inference to a population of 22,000. 45% of the sample reported having a chronic medical condition. The desired sample size was achieved and exceeded with three initial recruits and 10 waves of recruitment across 9 weeks. There was substantial cross-group mixing for recruitment in terms of sex and recency of immigration, which facilitated the emergence of diversity within recruitment chains. Primary factors that contributed to effective recruitment were location, flexibility, on-site childcare, and detailed explanation of the recruitment process. RDS is an effective recruitment method to study the health of undocumented Latinx immigrants, which is essential to informing intervention and policy., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: The relationship between dyspnoea, coronary artery disease (CAD), and major cardiovascular events (MACE) is poorly understood. This study evaluated (i) the association of dyspnoea with the severity of anatomical CAD by coronary computed tomography angiography (CCTA) and (ii) to which extent CAD explains MACE in patients with dyspnoea., Methods and Results: From the international COronary CT Angiography EvaluatioN for Clinical Outcomes: An InteRnational Multicenter (CONFIRM) registry, 4425 patients (750 with dyspnoea) with suspected but without known CAD were included and prospectively followed for ≥5 years. First, the association of dyspnoea with CAD severity was assessed using logistic regression analysis. Second, the prognostic value of dyspnoea for MACE (myocardial infarction and death), and specifically, the interaction between dyspnoea and CAD severity was investigated using Cox proportional-hazard analysis. Mean patient age was 60.3 ± 11.9 years, 63% of patients were male and 592 MACE events occurred during a median follow-up duration of 5.4 (IQR 5.1-6.0) years. On uni- and multivariable analysis (adjusting for age, sex, body mass index, chest pain typicality, and risk factors), dyspnoea was associated with two- and three-vessel/left main (LM) obstructive CAD. The presence of dyspnoea increased the risk for MACE [hazard ratio (HR) 1.57, 95% confidence interval (CI): 1.29-1.90], which was modified after adjusting for clinical predictors and CAD severity (HR 1.26, 95% CI: 1.02-1.55). Conversely, when stratified by CAD severity, dyspnoea did not provide incremental prognostic value in one-, two-, or three-vessel/LM obstructive CAD, but dyspnoea did provide incremental prognostic value in non-obstructive CAD., Conclusion: In patients with suspected CAD, dyspnoea was independently associated with severe obstructive CAD on CCTA. The severity of obstructive CAD explained the elevated MACE rates in patients presenting with dyspnoea, but in patients with non-obstructive CAD, dyspnoea portended additional risk., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: The ability to control the spread of COVID-19 continues to be hampered by a lack of rapid, scalable, and easily deployable diagnostic solutions., Methods: We developed a diagnostic method based on CRISPR (clustered regularly interspaced short palindromic repeats) that can deliver sensitive, specific, and high-throughput detection of Sudden Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). The assay utilizes SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing) for the qualitative detection of SARS-CoV-2 RNA and may be performed directly on a swab or saliva sample without nucleic acid extraction. The assay uses a 384-well format and provides results in <1 hour., Results: Assay performance was evaluated with 105 (55 negative, 50 positive) remnant SARS-CoV-2 specimens previously tested using Food and Drug Administration emergency use authorized assays and retested with a modified version of the Centers for Disease Control and Prevention (CDC) quantitative PCR with reverse transcription (RT-qPCR) assay. When combined with magnetic bead-based extraction, the high-throughput SHERLOCK SARS-CoV-2 assay was 100% concordant (n = 60) with the CDC RT-qPCR. When used with direct sample addition the high-throughput assay was also 100% concordant with the CDC RT-qPCR direct method (n = 45). With direct saliva sample addition, the negative and positive percentage agreements were 100% (15/15, 95% CI: 81.8-100%) and 88% (15/17, 95% CI: 63.6-98.5%), respectively, compared with results from a collaborating clinical laboratory., Conclusions: This high-throughput assay identifies SARS-CoV-2 from patient samples with or without nucleic acid extraction with high concordance to RT-qPCR methods. This test enables high complexity laboratories to rapidly increase their testing capacities with simple equipment., (© American Association for Clinical Chemistry 2021.)

As a result of the relatively few available antifungals and the increasing frequency of resistance to them, the development of novel antifungals is increasingly important. The plant natural product poacic acid (PA) inhibits β-1,3-glucan synthesis in Saccharomyces cerevisiae and has antifungal activity against a wide range of plant pathogens. However, the mode of action of PA is unclear. Here, we reveal that PA specifically binds to β-1,3-glucan, its affinity for which is ~30-fold that for chitin. Besides its effect on β-1,3-glucan synthase activity, PA inhibited the yeast glucan-elongating activity of Gas1 and Gas2 and the chitin-glucan transglycosylase activity of Crh1. Regarding the cellular response to PA, transcriptional co-regulation was mediated by parallel activation of the cell-wall integrity (CWI) and high-osmolarity glycerol signaling pathways. Despite targeting β-1,3-glucan remodeling, the transcriptional profiles and regulatory circuits activated by caspofungin, zymolyase, and PA differed, indicating that their effects on CWI have different mechanisms. The effects of PA on the growth of yeast strains indicated that it has a mode of action distinct from that of echinocandins, suggesting it is a unique antifungal agent., (© 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Background: The current study aimed to examine the independent prognostic value of whole-heart atherosclerosis progression by serial coronary computed tomography angiography (CCTA) for major adverse cardiovascular events (MACE)., Methods: The multi-center PARADIGM study includes patients undergoing serial CCTA for symptomatic reasons, ≥2 years apart. Whole-heart atherosclerosis was characterized on a segmental level, with co-registration of baseline and follow-up CCTA, and summed to per-patient level. The independent prognostic significance of atherosclerosis progression for MACE (non-fatal myocardial infarction [MI], death, unplanned coronary revascularization) was examined. Patients experiencing interval MACE were not omitted., Results: The study population comprised 1166 patients (age 60.5 ​± ​9.5 years, 54.7% male) who experienced 139 MACE events during 8.2 (IQR 6.2, 9.5) years of follow up (15 death, 5 non-fatal MI, 119 unplanned revascularizations). Whole-heart percent atheroma volume (PAV) increased from 2.32% at baseline to 4.04% at follow-up. Adjusted for baseline PAV, the annualized increase in PAV was independently associated with MACE: OR 1.23 (95% CI 1.08, 1.39) per 1 standard deviation increase, which was consistent in multiple subpopulations. When categorized by composition, only non-calcified plaque progression associated independently with MACE, while calcified plaque did not. Restricting to patients without events before follow-up CCTA, those with future MACE showed an annualized increase in PAV of 0.93% (IQR 0.34, 1.96) vs 0.32% (IQR 0.02, 0.90), P ​< ​0.001., Conclusions: Whole-heart atherosclerosis progression examined by serial CCTA is independently associated with MACE, with a prognostic threshold of 1.0% increase in PAV per year., Competing Interests: Declaration of competing interest Dr. James K. Min receives funding from the Dalio Foundation, National Institutes of Health, and GE Healthcare. Dr. Min serves on the scientific advisory board of Arineta and GE Healthcare, and has an equity interest in Cleerly. Dr. Habib Samady serves on the medical advisory board of Philips and has equity holding in Covanos. The remaining authors have no relevant disclosures., (Copyright © 2020 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

In the context of recent policies aimed at deterring immigration and criminalizing undocumented Latino immigrants, we examined factors predicting implicit and explicit attitudes toward this population. We hypothesized that more positive implicit and explicit attitudes toward undocumented Latino immigrants would be displayed by Latinxs (compared to non-Hispanic Whites) and by individuals having personal connections to undocumented immigrants or a high level of intercultural sensitivity. Latinx ( n = 376) and non-Hispanic White ( n = 214) college students (70% female, M age = 21) participated in this cross-sectional study and completed two Implicit Association Tests and measures of explicit attitudes, personal connections, and intercultural sensitivity. As predicted, Latinx participants held more positive implicit and explicit attitudes than non-Hispanic White participants. Intercultural sensitivity and personal connections to undocumented immigrants were associated with more positive explicit attitudes. Identifying factors that increase a sense of commonality and cultural sensitivity with undocumented Latino immigrants may be helpful in diminishing the profiling and criminalization of this community.

In Pseudomonas aeruginosa the alp system encodes a programmed cell death pathway that is switched on in a subset of cells in response to DNA damage and is linked to the virulence of the organism. Here we show that the central regulator of this pathway, AlpA, exerts its effects by acting as an antiterminator rather than a transcription activator. In particular, we present evidence that AlpA positively regulates the alpBCDE cell lysis genes, as well as genes in a second newly identified target locus, by recognizing specific DNA sites within the promoter, then binding RNA polymerase directly and allowing it to bypass intrinsic terminators positioned downstream. AlpA thus functions in a mechanistically unusual manner to control the expression of virulence genes in this opportunistic pathogen.

Background: Primary care is the major point of access in most health systems in developed countries and therefore for the detection of coronavirus disease 2019 (COVID-19) cases. The quality of its IT systems, together with access to the results of mass screening with Polymerase chain reaction (PCR) tests, makes it possible to analyse the impact of various concurrent factors on the likelihood of contracting the disease., Methods and Findings: Through data mining techniques with the sociodemographic and clinical variables recorded in patient's medical histories, a decision tree-based logistic regression model has been proposed which analyses the significance of demographic and clinical variables in the probability of having a positive PCR in a sample of 7,314 individuals treated in the Primary Care service of the public health system of Catalonia. The statistical approach to decision tree modelling allows 66.2% of diagnoses of infection by COVID-19 to be classified with a sensitivity of 64.3% and a specificity of 62.5%, with prior contact with a positive case being the primary predictor variable., Conclusions: The use of a classification tree model may be useful in screening for COVID-19 infection. Contact detection is the most reliable variable for detecting Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases. The model would support that, beyond a symptomatic diagnosis, the best way to detect cases would be to engage in contact tracing., Competing Interests: The authors have declared that no competing interests exist.

Resting state functional magnetic resonance imaging (rsfMRI), and the underlying brain networks identified with it, have recently appeared as a promising avenue for the evaluation of functional deficits without the need for active patient participation. We hypothesize here that such alteration can be inferred from tissue damage within the network. From an engineering perspective, the numerical prediction of tissue mechanical damage following an impact remains computationally expensive. To this end, we propose a numerical framework aimed at predicting resting state network disruption for an arbitrary head impact, as described by the head velocity, location and angle of impact, and impactor shape. The proposed method uses a library of precalculated cases leveraged by a machine learning layer for efficient and quick prediction. The accuracy of the machine learning layer is illustrated with a dummy fall case, where the machine learning prediction is shown to closely match the full simulation results. The resulting framework is finally tested against the rsfMRI data of nine TBI patients scanned within 24 h of injury, for which paramedical information was used to reconstruct in silico the accident. While more clinical data are required for full validation, this approach opens the door to (i) on-the-fly prediction of rsfMRI alterations, readily measurable on clinical premises from paramedical data, and (ii) reverse-engineered accident reconstruction through rsfMRI measurements., Competing Interests: JM-P was employed by the company Lurtis, Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Schroder, Lawrence, Voets, Garcia-Gonzalez, Jones, Peña and Jerusalem.)

From samples of the Paleozoic Tamatán Group (Huizachal-Peregrina Anticlinorium, Tamaulipas, Mexico), petrographic (qualitative and modal) and geochemical analyses (major, trace, and rare earth elements) were conducted. The first U-Pb geochronological data on detrital zircons of the Tamatán Group were generated using four samples. The data presented here contains a broad overview of photomicrography, recalculated modal point-count data, raw geochemical data, and simple statistics of selected geochemical parameters. The data presented in this article are interpreted and discussed in the research article titled "Provenance and tectonic setting of the Tamatán Paleozoic sequence, NE Mexico: Implications for the closure of the Rheic Ocean at the northwestern part of Gondwana" [1]., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships which have or could be perceived to have influenced the work reported in this article., (© 2021 The Authors.)

There is a worldwide growing use of chemicals by our developed, industrialized, and technological society. More than 100,000 chemical substances are thus commonly used both by industry and households. Depending on the amount produced, physical-chemical properties, and mode of use, many of them may reach the environment and, notably, the aquatic receiving systems. This may result in undesirable and harmful side-effects on both the human and the ecosystem's health. Mediterranean rivers are largely different from Northern and Central European rivers in terms of hydrological regime, climate conditions (e.g. air temperature, solar irradiation, precipitation), and socio-economics (e.g. land use, tourism, crop types, etc.), with all these factors leading to differences in the relative importance of the environmental stressors, in the classes and levels of the pollutants found and their environmental fate. Furthermore, water scarcity might be critical in affecting water pollution because of the lowered dilution capacity of chemicals. This work provides raw chemical data from different families of microcontaminants identified in three selected Mediterranean rivers (the Sava, Evrotas, and Adige) collected during two sampling campaigns conducted in 2014 and 2015 in three different matrices, namely, water, sediments, and biota (fish). More than 200 organic micropollutants were analyzed, including relevant groups like pharmaceuticals, personal care products, perfluorinated compounds, pesticides, pyrethroid insecticides, flame retardants, and persistent organic pollutants. Data obtained were summarized with some basic statistics for all compound families and matrices analyzed. Observed occurrence and spatial patterns were interpreted both in terms of compound physical-chemical properties and local environmental pressures. Finally, their spatial distribution was examined and their ecotoxicological risk in the water phase was assessed. This allowed locating, at each basin, the most polluted sites ("hot spots") and identifying the respective river basin specific pollutants (RBSPs), prioritizing them in terms of the potential ecotoxicological risk posed to the aquatic ecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Low-density lipoprotein cholesterol (LDL-C) is a target for cardiovascular prevention. Contemporary equations for LDL-C estimation have limited accuracy in certain scenarios (high triglycerides [TG], very low LDL-C)., Objectives: We derived a novel method for LDL-C estimation from the standard lipid profile using a machine learning (ML) approach utilizing random forests (the Weill Cornell model). We compared its correlation to direct LDL-C with the Friedewald and Martin-Hopkins equations for LDL-C estimation., Methods: The study cohort comprised a convenience sample of standard lipid profile measurements (with the directly measured components of total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], and TG) as well as chemical-based direct LDL-C performed on the same day at the New York-Presbyterian Hospital/Weill Cornell Medicine (NYP-WCM). Subsequently, an ML algorithm was used to construct a model for LDL-C estimation. Results are reported on the held-out test set, with correlation coefficients and absolute residuals used to assess model performance., Results: Between 2005 and 2019, there were 17,500 lipid profiles performed on 10,936 unique individuals (4,456 females; 40.8%) aged 1 to 103. Correlation coefficients between estimated and measured LDL-C values were 0.982 for the Weill Cornell model, compared to 0.950 for Friedewald and 0.962 for the Martin-Hopkins method. The Weill Cornell model was consistently better across subgroups stratified by LDL-C and TG values, including TG >500 and LDL-C <70., Conclusions: An ML model was found to have a better correlation with direct LDL-C than either the Friedewald formula or Martin-Hopkins equation, including in the setting of elevated TG and very low LDL-C., Competing Interests: Gurpreet Singh became affiliated with GlaxoSmithKline after working on this project. Benjamin C. Lee receives consulting fees from Cleerly Inc, but has not receive that consulting fee since 2019. Leslee J. Shaw reports having an equity interest in Cleerly Inc. There are no patents, products in development or marketed products associated with this research to declare This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background and Aims: Different methodologies to report whole-heart atherosclerotic plaque on coronary computed tomography angiography (CCTA) have been utilized. We examined which of the three commonly used plaque burden definitions was least affected by differences in body surface area (BSA) and sex., Methods: The PARADIGM study includes symptomatic patients with suspected coronary atherosclerosis who underwent serial CCTA >2 years apart. Coronary lumen, vessel, and plaque were quantified from the coronary tree on a 0.5 mm cross-sectional basis by a core-lab, and summed to per-patient. Three quantitative methods of plaque burden were employed: (1) total plaque volume (PV) in mm 3 , (2) percent atheroma volume (PAV) in % [which equaled: PV/vessel volume * 100%], and (3) normalized total atheroma volume (TAV norm ) in mm 3 [which equaled: PV/vessel length * mean population vessel length]. Only data from the baseline CCTA were used. PV, PAV, and TAV norm were compared between patients in the top quartile of BSA vs the remaining, and between sexes. Associations between vessel volume, BSA, and the three plaque burden methodologies were assessed., Results: The study population comprised 1479 patients (age 60.7 ± 9.3 years, 58.4% male) who underwent CCTA. A total of 17,649 coronary artery segments were evaluated with a median of 12 (IQR 11-13) segments per-patient (from a 16-segment coronary tree). Patients with a large BSA (top quartile), compared with the remaining patients, had a larger PV and TAV norm , but similar PAV. The relation between larger BSA and larger absolute plaque volume (PV and TAV norm ) was mediated by the coronary vessel volume. Independent from the atherosclerotic cardiovascular disease risk (ASCVD) score, vessel volume correlated with PV (P < 0.001), and TAV norm (P = 0.003), but not with PAV (P = 0.201). The three plaque burden methods were equally affected by sex., Conclusions: PAV was less affected by patient's body surface area then PV and TAV norm and may be the preferred method to report coronary atherosclerotic burden., Competing Interests: Declaration of competing interest Dr. James K. Min receives funding from the Dalio Foundation, National Institutes of Health, and GE Healthcare. Dr. Min serves on the scientific advisory board of Arineta and GE Healthcare, and has an equity interest in Cleerly. Dr. Habib Samady serves on the scientific advisory board of Philips, has equity interest in Covanos Inc., and has a research grant from Medtronic. Dr. Kavitha Chinnaiyan is a non-compensated medical advisory board member of Heartflow Inc. The remaining authors have no relevant disclosures., (Copyright © 2020. Published by Elsevier Inc.)

Introduction: There currently exist no quantitative methods to assess graft viability before the donor procurement procedure. In Europe, around 20% of liver grafts evaluated "in situ" by an experienced surgeon are discarded. The aim of this study is to evaluate the use of the plasma disappearance rate indocyanine green (PDR-ICG) clearance in predicting liver graft rejection to avoid this 20% of futile surgeries., Objectives: To evaluate PDR-ICG as a predictor of liver graft rejection in death brain donors compared with the gold standard evaluation by an experienced surgeon., Material and Methods: Prospective observational single center study. From March 2017 to July 2019, 29 donors were included in the study, 17 were men and 12 women with a median age of 68 years ± 16.9 years. Donors had an intensive care unit stay of 2 days ± 4 days. PDR-ICG was measured with PICCO2 monitor. Indocyanine green clearance dose was 0.25 mg/kg injected intravenously in the operating room just before donor procurement procedure is initiated. The surgeon was unaware of the PDR-ICG measure until the decision of graft acceptance was taken. Data regarding the donors and biopsy results were included in a prospective database., Results: PDR-ICG measure could be obtained in 10 minutes in all of the cases included. The median PDR-ICG obtained was 18%/min (range, 2.4-31%/min). Graft rejection took place in 15 out of the 29 donors. PDR-ICG value was less than 10%/min in 6 of these rejected grafts and less than 15%/min in 10 donors. All donor grafts with PDR-ICG <15% were discarded. The graft had been discarded in 5 donors with a PDR-ICG >15%., Conclusions: In our study a plasma disappearance rate <10 would have identified the grafts that would be rejected, thus avoiding the displacement work and expense of the surgical team. These results should be confirmed in a multicentric study., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aims: In patients without obstructive coronary artery disease (CAD), we examined the prognostic value of risk factors and atherosclerotic extent., Methods and Results: Patients from the long-term CONFIRM registry without prior CAD and without obstructive (≥50%) stenosis were included. Within the groups of normal coronary computed tomography angiography (CCTA) (N = 1849) and non-obstructive CAD (N = 1698), the prognostic value of traditional clinical risk factors and atherosclerotic extent (segment involvement score, SIS) was assessed with Cox models. Major adverse cardiac events (MACE) were defined as all-cause mortality, non-fatal myocardial infarction, or late revascularization. In total, 3547 patients were included (age 57.9 ± 12.1 years, 57.8% male), experiencing 460 MACE during 5.4 years of follow-up. Age, body mass index, hypertension, and diabetes were the clinical variables associated with increased MACE risk, but the magnitude of risk was higher for CCTA defined atherosclerotic extent; adjusted hazard ratio (HR) for SIS >5 was 3.4 (95% confidence interval [CI] 2.3-4.9) while HR for diabetes and hypertension were 1.7 (95% CI 1.3-2.2) and 1.4 (95% CI 1.1-1.7), respectively. Exclusion of revascularization as endpoint did not modify the results. In normal CCTA, presence of ≥1 traditional risk factors did not worsen prognosis (log-rank P = 0.248), while it did in non-obstructive CAD (log-rank P = 0.025). Adjusted for SIS, hypertension and diabetes predicted MACE risk in non-obstructive CAD, while diabetes did not increase risk in absence of CAD (P-interaction = 0.004)., Conclusion: Among patients without obstructive CAD, the extent of CAD provides more prognostic information for MACE than traditional cardiovascular risk factors. An interaction was observed between risk factors and CAD burden, suggesting synergistic effects of both., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)