Critical Assessment of Metagenome Interpretation: the second round of challenges.

Evaluating metagenomic software is key for optimizing metagenome interpretation and focus of the Initiative for the Critical Assessment of Metagenome Interpretation (CAMI). The CAMI II challenge engaged the community to assess methods on realistic and complex datasets with long- and short-read sequences, created computationally from around 1,700 new and known genomes, as well as 600 new plasmids and viruses. Here we analyze 5,002 results by 76 program versions. Substantial improvements were seen in assembly, some due to long-read data. Related strains still were challenging for assembly and genome recovery through binning, as was assembly quality for the latter. Profilers markedly matured, with taxon profilers and binners excelling at higher bacterial ranks, but underperforming for viruses and Archaea. Clinical pathogen detection results revealed a need to improve reproducibility. Runtime and memory usage analyses identified efficient programs, including top performers with other metrics. The results identify challenges and guide researchers in selecting methods for analyses.

Prevention of schizophrenia deficits via non-invasive adolescent frontal cortex stimulation in rats.

Schizophrenia is a severe neurodevelopmental psychiatric affliction manifested behaviorally at late adolescence/early adulthood. Current treatments comprise antipsychotics which act solely symptomatic, are limited in their effectiveness and often associated with side-effects. We here report that application of non-invasive transcranial direct current stimulation (tDCS) during adolescence, prior to schizophrenia-relevant behavioral manifestation, prevents the development of positive symptoms and related neurobiological alterations in the maternal immune stimulation (MIS) model of schizophrenia.

Optimal use of lipid-lowering therapy after acute coronary syndromes: A Position Paper endorsed by the International Lipid Expert Panel (ILEP).

Atherosclerotic cardiovascular disease (ASCVD) and consequent acute coronary syndromes (ACS) are substantial contributors to morbidity and mortality across Europe. Much of these diseases burden is modifiable, in particular by lipid-lowering therapy (LLT). Current guidelines are based on the sound premise that with respect to low density lipoprotein cholesterol (LDL-C), "lower is better for longer", and the recent data have strongly emphasized the need of also "the earlier the better". In addition to statins, which have been available for several decades, the availability of ezetimibe and inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) are additional very effective approach to LLT, especially for those at very high and extremely high cardiovascular risk. LLT is initiated as a response to an individual's calculated risk of future ASCVD and is intensified over time in order to meet treatment goals. However, in real-life clinical practice goals are not met in a substantial proportion of patients. This Position Paper complements existing guidelines on the management of lipids in patients following ACS. Bearing in mind the very high risk of further events in ACS, we propose practical solutions focusing on immediate combination therapy in strict clinical scenarios, to improve access and adherence to LLT in these patients. We also define an 'Extremely High Risk' group of individuals following ACS, completing the attempt made in the recent European guidelines, and suggest mechanisms to urgently address lipid-medicated cardiovascular risk in these patients.

Ticagrelor Utilization in Patients With Non-ST Elevation Acute Coronary Syndromes in Romania.

BACKGROUND: Dual antiplatelet therapy (DAPT) represents a major tool of non-ST elevation acute coronary syndrome (NSTE-ACS) management. The real-world usage of potent P2Y12 inhibitors within DAPT in middle-income countries is poorly described. STUDY QUESTION: To assess the factors that influence P2Y12 inhibitor choice at discharge in invasively managed NSTE-ACS patients, without an indication for oral anticoagulation, treated across Romania. STUDY DESIGN: The Romanian National NSTE-ACS Registry allows the consecutive enrollment of NSTE-ACS patients admitted in 11 (of 24) interventional centers reimbursed from public funds. MEASURES AND OUTCOMES: NSTE-ACS patients that received DAPT at discharge were identified. Deceased patients, those with an indication for oral anticoagulation or not receiving DAPT at discharge, were excluded. P2Y12 inhibitor choice was analyzed based on demographic, clinical, and invasive management characteristics. RESULTS: One thousand fifty (63 ± 10 years, 73% male) of 1418 patients enrolled between 2016 and 2019 were analyzed. The P2Y12 inhibitor pretreatment rate was 90%. Obstructive coronary artery disease was found in 95.3% of patients. 84.6% underwent percutaneous coronary interventions (PCIs). Single vessel PCI was reported in 84% of PCI patients. The clopidogrel usage rate was 49.6%, ticagrelor 50.0%, and prasugrel 0.4%. Overall, higher ticagrelor usage was associated with: non-ST elevation myocardial infarction (P 0.035), age below 65 (P < 0.001), prior treatment with ticagrelor (P < 0.001), PCI during admission (P < 0.001), and its full 12-month reimbursement (since November 2017). Reimbursement increased the use of ticagrelor from 23.7% in 2016-2017 to 56.9% in 2018-2019 (P < 0.001). In PCI patients, ticagrelor use was associated with PCI with stenting (P 0.016) and multivessel PCI (0.013). CONCLUSIONS: DAPT, P2Y12 inhibitor pretreatment, and single vessel PCI are the standards of care in invasively managed NSTE-ACS patients in Romania. Besides the clinical and invasive characteristics that favor its use, the full reimbursement of ticagrelor introduced in November 2017 doubled its yearly usage.

Keeping up with the genomes: efficient learning of our increasing knowledge of the tree of life.

BACKGROUND: It is a computational challenge for current metagenomic classifiers to keep up with the pace of training data generated from genome sequencing projects, such as the exponentially-growing NCBI RefSeq bacterial genome database. When new reference sequences are added to training data, statically trained classifiers must be rerun on all data, resulting in a highly inefficient process. The rich literature of "incremental learning" addresses the need to update an existing classifier to accommodate new data without sacrificing much accuracy compared to retraining the classifier with all data. RESULTS: We demonstrate how classification improves over time by incrementally training a classifier on progressive RefSeq snapshots and testing it on: (a) all known current genomes (as a ground truth set) and (b) a real experimental metagenomic gut sample. We demonstrate that as a classifier model's knowledge of genomes grows, classification accuracy increases. The proof-of-concept naïve Bayes implementation, when updated yearly, now runs in 1/4th of the non-incremental time with no accuracy loss. CONCLUSIONS: It is evident that classification improves by having the most current knowledge at its disposal. Therefore, it is of utmost importance to make classifiers computationally tractable to keep up with the data deluge. The incremental learning classifier can be efficiently updated without the cost of reprocessing nor the access to the existing database and therefore save storage as well as computation resources.

GOOD TO KNOW: The ALPPS Procedure - Embracing a New Technique.

BACKGROUND: Hepatic resection is the only potentially curative treatment for primary liver tumors and hepatic metastases. The most frightening postoperative complication of extensive hepatectomies is liver failure due to insufficient future liver remnant (FLR). The ALPPS technique (Associating Liver Partition and Portal vein Ligation for Staged hepatectomy) effectively increased the resectability of otherwise inoperable liver tumors (primary or secondary malignant liver tumor) by achieving a rapid and an effective hypertrophy of the FLR, which lowers postoperative liver failure risk. AIM: To present the ALPPS classic right trisectionectomy and its technical variants which were invented to decrease the high rate of post-operative morbidity and mortality, reported in early case series. TECHNIQUE: ALPPS involves two stages. The first surgical procedure consists in the ligation of the right portal branch and the partition of the liver at the site of the falciform ligament (insitu splitting). In contrast to a classical hepatectomy, the tumoral hemiliver is left in situ and remains vascularized by the right hepatic artery only. The biliary and systemic venous drainages represented by the right biliary duct and respectively the hepatic veins, are preserved. The second step of the procedure is usually performed within 7 to 15 days after the firststage. The tumoral hemiliver is removed by sectioning the right hepatic artery, the biliary duct and the systemic venous pedicle. Conclusions: The ALPPS technique is a therapeutic method for inoperable liver tumors by standard methods of hepatectomy ± portal vein ligation (PVL). By careful patient selection and technical adjustment to the particular conditions of each case, better outcomes have been achieved, leading toan increasing number of surgeons who perform ALPPS.

Bicuspid Aortic Valves and Transcatheter Valve Replacement: Feasibility and Safety.

In the last few years, transcatheter aortic valve replacement (TAVR) has rapidly become the standard of care for severe symptomatic aortic stenosis (AS). If initially it was preferred only for high-risk surgical patients, now even low-risk patients are eligible candidates. There were several factors to consider why patients with bicuspid aortic valves (BAVs) were omitted from these trials. However, it should be noted that bicuspid AS is not unusual among patients who experience transcatheter valve implantation. The TAVR procedure in BAV is a reliable and safe treatment option for surgical aortic valve replacement (SAVR) but it is associated with an elevated incidence of paravalvular regurgitation (PVR) and the likelihood of implanting a permanent pacemaker. Bicuspid valves do not appear to be a contraindication to TAVI according to current data, but further specific clinical trials will be required to confirm this conclusion.

Progress Toward Reversed Uterine Diastolic Flow in the Third Trimester - An Inauspicious Sign.

BACKGROUND: Increased uteroplacental resistance is associated with high uterine artery pulsatility and resistance indices and early diastolic notching. Evolution toward reversed diastolic uterine flow in the third trimester was scarcely reported previously. The feature was related to severe complications for both mother and fetus. MATERIAL AND METHODS: Data were collected from 3638 pregnancies undergoing prenatal care in our hospital. In this study, we aimed to identify those pregnancies with development of a reversed diastolic flow at the spectral Doppler interrogation of uterine arteries later than 24 weeks of gestation. A secondary aim was to follow up and actively manage these pregnancies. RESULTS: Previously, reversed uterine diastolic flow was reported during the third trimester in four cases only. In our study three pregnancies only developed reversed uterine arteries diastolic flow, none being associated with preeclampsia. All cases evolved with complications at birth. CONCLUSIONS: Progressive deterioration of uterine arteries flow is possible during pregnancy. Reversed diastolic flow is a rare occurrence in the third trimester of pregnancy. Based on current knowledge, it may be considered an ominous sign and should trigger a close follow-up. Future studies using routine investigation of uterine arteries flow late in pregnancy may prove informative.

Non-Aqueous Electrodeposition and Characterization of AlCrCuFeNi High Entropy Alloy Thin Films.

Materials used in the marine industry are exposed to extreme conditions, so it is necessary to meet remarkable characteristics, such as mechanical resistance, low density, and good corrosion resistance. The challenging environment requires continuous performance improvements, so this work is focused on developing new materials with superior properties, using the electrochemical deposition technique, which are convenient for marine engineering. High-entropy alloys have been attracting tremendous interest in many applications, due to their simple crystal structures and advantageous physical-chemical properties, such as high strength, anti-corrosion, erosion, and electro-magnetic capabilities. To identify the most appropriate compositions, MatCalc software was used to predict the structure and characteristics of the required materials, and thermodynamic and kinetic criteria calculations were performed. The modelling processes generated a series of optimal compositions in the AlCrCuFeNi alloy system, that are suitable to be used in anticorrosive and tribological applications. The composition and morphology of the obtained high entropy alloy thin films revealed a uniform structure, with a small grain profile. The corrosion resistance was investigated in artificial seawater to observe the behavior of the newly developed materials in demanding conditions, and the results showed improved results compared to the copper foil substrate.

Antithrombotic Strategies in Invasively Managed Patients with Non-ST Elevation Acute Coronary Syndromes and Non-Valvular Atrial Fibrillation in Romania.

Introduction: Concomitant atrial fibrillation (AF) in non-ST segment elevation acute coronary syndrome (NSTE-ACS) patients complicates the decision-making process regarding short- and long-term antithrombotic strategies. Patient profiles and usage rates of different antithrombotic combinations in this patient subgroup in Romania are poorly described. Premises and objectives: To describe the characteristics of invasively managed NSTE-ACS patients with AF (either known or newly diagnosed) compared to patients with no oral anticoagulation (OAC) indications, and analyze the rates and factors that influence the different antithrombotic regimens at discharge in AF patients. Material and methods: The Romanian National NSTE-ACS Registry allows the enrollment of invasively managed NSTE-ACS patients admitted in 11 interventional centers. Patients with non-valvular AF and no other OAC indication were identified and compared with patients with no indication for OAC. The antithrombotic strategy at discharge was analyzed based on demographic, clinical, and invasive management characteristics. Outcomes:A total of 1418 patients were enrolled between 2016 and 2019 out of which, 175 AF subjects and 1159 patients with no OAC indication were included in the analysis. Subjects with AF were older (70 ± 8.3 vs 62.9 ± 10.4 years, p <0.001) and more likely to have a GRACE score >140 (aOR 2.28, 95% CI 1.58-3.31, p<0.001), a history of heart failure (aOR 3.07, 95% CI 2.14-4.41, p <0.001), dementia or Alzheimer disease (aOR 3.45, 95% CI 1.11-10.68, p 0.032), and non-fatal major cardiovascular (CV) events during admission (aOR 6.71, 95% CI 1.61-27.94, p 0.009). Globally, triple antithrombotic therapy (TAT) was used in 52.5% of AF patients. 69% of PCI patients received TAT. One in four patients with AF did not receive OAC at discharge. Prior treatment with OAC was the strongest predictor for OAC usage at discharge (aOR 12.34, 95% CI 3.21-47.61, p<0.001). Conclusion: More than one in 10 NSTE-ACS patients have a concomitant non-valvular AF diagnosis. These patients are significantly older and are more likely to have significant CV and non-CV disease. Triple antithrombotic therapy is the most used antithrombotic strategy, especially in the PCI subgroup. One in four NSTE-ACS AF patients do not receive OAC at discharge.

Thapsigargin Is a Broad-Spectrum Inhibitor of Major Human Respiratory Viruses: Coronavirus, Respiratory Syncytial Virus and Influenza A Virus.

The long-term control strategy of SARS-CoV-2 and other major respiratory viruses needs to include antivirals to treat acute infections, in addition to the judicious use of effective vaccines. Whilst COVID-19 vaccines are being rolled out for mass vaccination, the modest number of antivirals in use or development for any disease bears testament to the challenges of antiviral development. We recently showed that non-cytotoxic levels of thapsigargin (TG), an inhibitor of the sarcoplasmic/endoplasmic reticulum (ER) Ca2+ ATPase pump, induces a potent host innate immune antiviral response that blocks influenza A virus replication. Here we show that TG is also highly effective in blocking the replication of respiratory syncytial virus (RSV), common cold coronavirus OC43, SARS-CoV-2 and influenza A virus in immortalized or primary human cells. TG's antiviral performance was significantly better than remdesivir and ribavirin in their respective inhibition of OC43 and RSV. Notably, TG was just as inhibitory to coronaviruses (OC43 and SARS-CoV-2) and influenza viruses (USSR H1N1 and pdm 2009 H1N1) in separate infections as in co-infections. Post-infection oral gavage of acid-stable TG protected mice against a lethal influenza virus challenge. Together with its ability to inhibit the different viruses before or during active infection, and with an antiviral duration of at least 48 h post-TG exposure, we propose that TG (or its derivatives) is a promising broad-spectrum inhibitor against SARS-CoV-2, OC43, RSV and influenza virus.

The Romanian National Registry of non-ST Elevation Acute Coronary Syndromes - Design and Rationale.

Introduction:Non-ST segment elevation acute coronary syndromes (NSTE-ACS) form a large part of the number of annual emergency admissions in the Cardiology Departments in Romania, representing a significant burden on the health care system resources. The European Society of Cardiology (ESC) guidelines for the diagnosis and treatment of NSTE-ACS patients represent ideal standards, which are difficult to implement, given the significant differences in the socio-economic climates of the various European Union countries, as the access to modern reperfusion techniques for NSTE-ACS patients, including Romania, is usually suboptimal. Objectives:The evaluate the current implementation state of the ESC recommended protocols for the diagnosis and treatment of NSTE-ACS patients in Romania. There are no data regarding the number of patients who benefit from modern revascularization techniques, the time intervals between symptom onset, positive diagnosis and revascularization procedures, and the impact of these strategies on in-hospital and one-year mortality Materials and methods:We support the development of an online National Registry of NSTE-ACS patients, in which data obtained from the in-hospital medical records of patients undergoing invasive management will be prospectively recorded. The platform will initially be accessible to 11 interventional centers, and will include patients diagnosed and treated according to local protocols. Patient status at one year after the acute event will also be recorded. The Registry will eventually be accessible to any center in Romania caring for NSTE-ACS patients. The recorded variables will be based on those with a significant impact on the time from symptom onset to the positive diagnosis, type of clinical presentation, appropriate treatment initiation and the type of applied treatment. Eexpected outcomes:Local clinical expertise, the number of treated patients and center-level technical barriers are expected to significantly influence the reported diagnostic and therapeutic measures. The performance of the various local in-hospital guidelines and transfer protocols between non-interventional and interventional centers will be analyzed, based on which recommendations and objectives can be defined in order to optimize the ESC guidelines implementation. Conclusion:The National Registry of non-ST elevation acute coronary syndromes will provide an essential tool that facilitates the implementation of optimal ESC guideline-driven diagnostic and treatment measures, by adapting its recommendations to the socio-economic status in Romania and ensuring the best possible outcomes for the NSTE-ACS patient.

Ferroelectric triggering of carbon monoxide adsorption on lead zirco-titanate (001) surfaces.

Atomically clean lead zirco-titanate PbZr0.2Ti0.8O3 (001) layers exhibit a polarization oriented inwards P(-), visible by a band bending of all core levels towards lower binding energies, whereas as introduced layers exhibit P(+) polarization under air or in ultrahigh vacuum. The magnitude of the inwards polarization decreases when the temperature is increased at 700 K. CO adsorption on P(-) polarized surfaces saturates at about one quarter of a monolayer of carbon, and occurs in both molecular (oxidized) and dissociated (reduced) states of carbon, with a large majority of reduced state. The sticking of CO on the surface in ultrahigh vacuum is found to be directly related to the P(-) polarization state of the surface. A simple electrostatic mechanism is proposed to explain these dissociation processes and the sticking of carbon on P(-) polarized areas. Carbon desorbs also when the surface is irradiated with soft X-rays. Carbon desorption when the polarization is lost proceeds most probably in form of CO2. Upon carbon desorption cycles, the ferroelectric surface is depleted in oxygen and at some point reverses its polarization, owing to electrons provided by oxygen vacancies which are able to screen the depolarization field produced by positive fixed charges at the surface.