A proposed metric set for evaluation of genome assembly quality.

Quality control is essential for genome assemblies; however, a consensus has yet to be reached on what metrics should be adopted for the evaluation of assembly quality. N50 is widely used for contiguity measurement, but its effectiveness is constantly in question. Prevailing metrics for the completeness evaluation focus on gene space, yet challenging areas such as tandem repeats are commonly overlooked. Achieving correctness has become an indispensable dimension for quality control, while prevailing assembly releases lack scores reflecting this aspect. We propose a metric set with a set of statistic indexes for effective, comprehensive evaluation of assemblies and provide a score of a finished assembly for each metric, which can be utilized as a benchmark for achieving high-quality genome assemblies.

The diagnosis of cerebral palsy in two Danish national registries: a validation study.

AIMS: To determine the quality of prospectively collected data from the highly specialized Danish Cerebral Palsy Follow-up Program (CPOP), and to establish the validity of a reported cerebral palsy (CP) diagnosis in the Danish National Patient Registry (NPR), regularly used as a proxy for neurodevelopmental disorders in epidemiological research. METHODS: We compared data from the two registries on children with registered CP, born in Denmark between 2008 and 2009, with information from medical records verified by two experienced physicians specializing in pediatric neurology. Data accuracy was estimated by completeness, correctness, and reliability. Completeness was calculated as the number of cases with correctly registered CP diagnoses divided by the total number of true CP diagnoses (similar to sensitivity). Correctness was calculated as the number of cases with correct registrations divided by the total number of cases (similar to positive predictive value). Reliability was estimated using kappa statistics. RESULTS: Registered CP diagnoses in the CPOP had high accuracy, with 94% correctness and 91% completeness. Furthermore, most key variables in the CPOP showed excellent reliability, especially variables defining the severity of the condition. In the Danish NPR, only 225 of 348 children with a noted CP diagnosis fulfilled the diagnostic criteria for CP, resulting in 65% correctness. CONCLUSIONS: Danish CPOP data are a valid source for epidemiological research. Conversely, a noted CP diagnosis in the Danish NPR was, at best, correct in only two out of three patients.

Validity of self-reported educational level in the Tromsø Study.

BACKGROUND: Self-reported data on educational level have been collected for decades in the Tromsø Study, but their validity has yet to be established. AIM: To investigate the completeness and correctness of self-reported educational level in the Tromsø Study, using data from Statistics Norway. In addition, we explored the consequence of using these two data sources on educational trends in cardiometabolic diseases. METHODS: We compared self-reported and Statistics Norway-recorded educational level (primary, upper secondary, college/university <4 years, and college/university ⩾4 years) among 20,615 participants in the seventh survey of the Tromsø Study (Tromsø7, 2015-2016). Sensitivity, positive predictive value and weighted kappa were used to measure the validity of self-reported educational level in three age groups (40-52, 53-62, 63-99 years). Multivariable logistic regression was used to compare educational trends in cardiometabolic diseases between self-reported and Statistics Norway-recorded educational level. RESULTS: Sensitivity of self-reported educational level was highest among those with a college/university education of 4 years or more (⩾97% in all age groups and both sexes). Sensitivity for primary educational level ranged from 67% to 92% (all age groups and both sexes). The lowest positive predictive value was observed among women with a college/university education of 4 years or more (29-46%). Weighted kappa was substantial (0.52-0.59) among men and moderate to substantial (0.41-0.51) among women. Educational trends in the risk of cardiometabolic diseases were less pronounced when self-reported educational level was used. CONCLUSIONS: Self-reported educational level in Tromsø7 is adequately complete and correct. Self-reported data may produce weaker associations between educational level and cardiometabolic diseases than registry-based data.

Exploring the potential of ChatGPT as a supplementary tool for providing orthopaedic information.

PURPOSE: To investigate the potential use of large language models (LLMs) in orthopaedics by presenting queries pertinent to anterior cruciate ligament (ACL) surgery to generative pre-trained transformer (ChatGPT, specifically using its GPT-4 model of March 14th 2023). Additionally, this study aimed to evaluate the depth of the LLM's knowledge and investigate its adaptability to different user groups. It was hypothesized that the ChatGPT would be able to adapt to different target groups due to its strong language understanding and processing capabilities. METHODS: ChatGPT was presented with 20 questions and response was requested for two distinct target audiences: patients and non-orthopaedic medical doctors. Two board-certified orthopaedic sports medicine surgeons and two expert orthopaedic sports medicine surgeons independently evaluated the responses generated by ChatGPT. Mean correctness, completeness, and adaptability to the target audiences (patients and non-orthopaedic medical doctors) were determined. A three-point response scale facilitated nuanced assessment. RESULTS: ChatGPT exhibited fair accuracy, with average correctness scores of 1.69 and 1.66 (on a scale from 0, incorrect, 1, partially correct, to 2, correct) for patients and medical doctors, respectively. Three of the 20 questions (15.0%) were deemed incorrect by any of the four orthopaedic sports medicine surgeon assessors. Moreover, overall completeness was calculated to be 1.51 and 1.64 for patients and medical doctors, respectively, while overall adaptiveness was determined to be 1.75 and 1.73 for patients and doctors, respectively. CONCLUSION: Overall, ChatGPT was successful in generating correct responses in approximately 65% of the cases related to ACL surgery. The findings of this study imply that LLMs offer potential as a supplementary tool for acquiring orthopaedic knowledge. However, although ChatGPT can provide guidance and effectively adapt to diverse target audiences, it cannot supplant the expertise of orthopaedic sports medicine surgeons in diagnostic and treatment planning endeavours due to its limited understanding of orthopaedic domains and its potential for erroneous responses. LEVEL OF EVIDENCE: V.

On the Analysis of Regularized Fuzzy Systems of Uncertain Differential Equations.

This article analyzes a regularized set of fuzzy differential equations with respect to an uncertain parameter. We provide sufficient conditions for the correctness of a new regularization scheme. For the resulting family of regularized fuzzy differential equations, the following properties are analyzed, and efficient criteria are proposed: successive approximations, continuity, global existence of solutions, existence of approximate solutions, existence of solutions in the autonomous case. In addition, we develop stability criteria for the regularized family of fuzzy differential equations on the basis of the comparison technique and the method of nonlinear integral inequalities. We expect that the derived results will inspire future research work in this direction.

Counterfactual Anonymous Quantum Teleportation in the Presence of Adversarial Attacks and Channel Noise.

Hiding the identity of involved participants in the network, known as anonymity, is a crucial issue in some cryptographic applications such as electronic voting systems, auctions, digital signatures, and Byzantine agreements. This paper proposes a new anonymous quantum teleportation protocol based on counterfactual communication where no information-carrying particles pass through the channel. It is achieved by the distribution of a counterfactual entanglement among the participants in the network followed by the establishment of an anonymous entanglement between the sender and the receiver. Afterwards, the sender can anonymously teleport a quantum state to the receiver by utilizing the anonymous entanglement. However, the practicality of the anonymous quantum network mainly calls for two performance measures-robustness against adversarial attacks and noisy environments. Motivated by these demands, firstly, we prove the security of our proposed protocol and show that it achieves both the sender and receiver's anonymity in the presence of active adversaries and untrusted parties. Along with anonymity, we also ensure the correctness of the protocol and the privacy of the teleported qubit. Finally, we analyze the robustness of our proposed protocol under the presence of channel noise and compare its fidelity with those of the conventional protocols. The main advantage of our proposed protocol is that it can provide useful anonymous quantum resources for teleportation under noisy environment with a higher security compared to previous protocols.

Development and implementation of an LIS-based validation system for autoverification toward zero defects in the automated reporting of laboratory test results.

BACKGROUND: Validation of the autoverification function is one of the critical steps to confirm its effectiveness before use. It is crucial to verify whether the programmed algorithm follows the expected logic and produces the expected results. This process has always relied on the assessment of human-machine consistency and is mostly a manually recorded and time-consuming activity with inherent subjectivity and arbitrariness that cannot guarantee a comprehensive, timely and continuous effectiveness evaluation of the autoverification function. To overcome these inherent limitations, we independently developed and implemented a laboratory information system (LIS)-based validation system for autoverification. METHODS: We developed a correctness verification and integrity validation method (hereinafter referred to as the "new method") in the form of a human-machine dialog. The system records personnel review steps and determines whether the human-machine review results are consistent. Laboratory personnel then analyze the reasons for any inconsistency according to system prompts, add to or modify rules, reverify, and finally improve the accuracy of autoverification. RESULTS: The validation system was successfully established and implemented. For a dataset consisting of 833 rules for 30 assays, 782 rules (93.87%) were successfully verified in the correctness verification phase, and 51 rules were deleted due to execution errors. In the integrity validation phase, 24 projects were easily verified, while the other 6 projects still required the additional rules or changes to the rule settings. Taking the Hepatitis B virus test as an example, from the setting of 65 rules to the automated releasing of 3000 reports, the validation time was reduced from 452 (manual verification) to 275 h (new method), a reduction in validation time of 177 h. Furthermore, 94.6% (168/182) of laboratory users believed the new method greatly reduced the workload, effectively controlled the report risk and felt satisfied. Since 2019, over 3.5 million reports have been automatically reviewed and issued without a single clinical complaint. CONCLUSION: To the best of our knowledge, this is the first report to realize autoverification validation as a human-machine interaction. The new method effectively controls the risks of autoverification, shortens time consumption, and improves the efficiency of laboratory verification.

Toward a more holistic method of genome assembly assessment.

BACKGROUND: A key use of high throughput sequencing technology is the sequencing and assembly of full genome sequences. These genome assemblies are commonly assessed using statistics relating to contiguity of the assembly. Measures of contiguity are not strongly correlated with information about the biological completion or correctness of the assembly, and a commonly reported metric, N50, can be misleading. Over the years, multiple research groups have rejected the overuse of N50 and sought to develop more informative metrics. RESULTS: This paper presents a review of problems that arise from relying solely on contiguity as a measure of genome assembly quality as well as current alternative methods. Alternative methods are compared on the basis of how informative they are about the biological quality of the assembly and how easy they are to use. A comprehensive method for using multiple metrics of measuring assembly quality is presented. CONCLUSIONS: This study aims to report on the status of assembly assessment methods and compare them, as well as to offer a comprehensive method that incorporates multiple facets of quality assessment. Weaknesses and strengths of varying methods are presented and explained, with recommendations based on speed of analysis and user friendliness.

CPRD Aurum database: Assessment of data quality and completeness of three important comorbidities.

PURPOSE: The Clinical Practice Research Datalink (CPRD) now provides a new medical record database, CPRD Aurum. This is the second of several studies being undertaken to assess the quality of CPRD Aurum data for research. METHODS: We included patients aged 20+, with at least one lab test result of any type from a random sample of 50 000 patients in CPRD Aurum. We assessed whether diagnosis codes for type 2 diabetes, hyperlipidemia, and iron deficiency or unspecified anemia were accompanied by supporting codes including lab results and treatments (correctness) and whether lab results, treatments, or other codes indicate a missing diagnosis record (completeness). RESULTS: Among 37 502 patients in CPRD Aurum, correctness of type 2 diabetes, hyperlipidemia, and anemia diagnoses was high (99%, 93%, and 97%, respectively). Completeness was only high for type 2 diabetes (94%-98%); completeness for hypercholesterolemia and anemia diagnoses was modest even when the presence of treatments and lab results indicated the conditions were likely present (51%-59% and 58%-70%, respectively). CONCLUSIONS: Our findings indicate that for studies of type 2 diabetes, hyperlipidemia, and iron deficiency or unspecified anemia, the diagnosis code is likely to be correct where present. However, a significant proportion of cases of hyperlipidemia or anemia will be missed if only diagnosis codes are used to select patients with these conditions. Researchers should consider using treatments, supporting codes, and, when available, lab data to supplement diagnosis codes and enhance case capture when including these conditions in studies using CPRD Aurum.

Completeness and correctness of acute myocardial infarction diagnoses in a medical quality register and an administrative health register.

Aims: Health registers are used for administrative purposes, disease surveillance, quality assessment, and research. The value of the registers is entirely dependent on the quality of their data. The aim of this study was to investigate and compare the completeness and correctness of the acute myocardial infarction (AMI) diagnosis in the Norwegian Myocardial Infarction Register and in the Norwegian Patient Register. Methods: All Norwegian patients admitted directly to St Olavs hospital, Trondheim University Hospital, Trondheim University Hospital from 1 July to 31 December 2012 and who had plasma levels of cardiac troponin T measured during their hospitalization (n=4835 unique individuals, n=5882 hospitalizations) were identified in the hospital biochemical database. A gold standard for AMI was established by evaluation of maximum troponin T levels and by review of the information in the medical records. Cases of AMI in the registers were classified as true positive, false positive, true negative, and false negative according to the gold standard. We calculated sensitivity, positive predictive value (PPV), specificity, and negative predictive value (NPV). Results: The Norwegian Myocardial Infarction Register had a sensitivity of 86.0% (95% confidence interval (CI) 82.8-89.3%), PPV of 97.9% (96.4-99.3%), and specificity of 99.9% and NPV of 98.9% (98.6-99.2%) (99.8-100%). The corresponding figures for the Norwegian Patient Register were 85.8% (95% CI 82.5-89.1%), 95.1% (92.9-97.2%), and 99.7% (99.5-99.8%) and 98.9% (98.6-99.2%), respectively. Both registers had a sensitivity higher than 95% when compared to hospital discharge diagnoses. The results were similar for men and women and for cases below and above 80 years of age. Conclusions: The Norwegian Myocardial Infarction Register and the Norwegian Patient Register are adequately complete and correct for administrative purposes, disease surveillance, quality assessment, and research.

Feasibility analysis of conducting observational studies with the electronic health record.

BACKGROUND: The secondary use of electronic health records (EHRs) promises to facilitate medical research. We reviewed general data requirements in observational studies and analyzed the feasibility of conducting observational studies with structured EHR data, in particular diagnosis and procedure codes. METHODS: After reviewing published observational studies from the University Hospital of Erlangen for general data requirements, we identified three different study populations for the feasibility analysis with eligibility criteria from three exemplary observational studies. For each study population, we evaluated the availability of relevant patient characteristics in our EHR, including outcome and exposure variables. To assess data quality, we computed distributions of relevant patient characteristics from the available structured EHR data and compared them to those of the original studies. We implemented computed phenotypes for patient characteristics where necessary. In random samples, we evaluated how well structured patient characteristics agreed with a gold standard from manually interpreted free texts. We categorized our findings using the four data quality dimensions "completeness", "correctness", "currency" and "granularity". RESULTS: Reviewing general data requirements, we found that some investigators supplement routine data with questionnaires, interviews and follow-up examinations. We included 847 subjects in the feasibility analysis (Study 1 n = 411, Study 2 n = 423, Study 3 n = 13). All eligibility criteria from two studies were available in structured data, while one study required computed phenotypes in eligibility criteria. In one study, we found that all necessary patient characteristics were documented at least once in either structured or unstructured data. In another study, all exposure and outcome variables were available in structured data, while in the other one unstructured data had to be consulted. The comparison of patient characteristics distributions, as computed from structured data, with those from the original study yielded similar distributions as well as indications of underreporting. We observed violations in all four data quality dimensions. CONCLUSIONS: While we found relevant patient characteristics available in structured EHR data, data quality problems may entail that it remains a case-by-case decision whether diagnosis and procedure codes are sufficient to underpin observational studies. Free-text data or subsequently supplementary study data may be important to complement a comprehensive patient history.

A Comprehensive Technological Survey on the Dependable Self-Management CPS: From Self-Adaptive Architecture to Self-Management Strategies.

Cyber Physical Systems (CPS) has been a popular research area in the last decade. The dependability of CPS is still a critical issue, and few surveys have been published in this domain. CPS is a dynamic complex system, which involves various multidisciplinary technologies. To avoid human errors and to simplify management, self-management CPS (SCPS) is a wise choice. To achieve dependable self-management, systematic solutions are necessary to verify the design and to guarantee the safety of self-adaptation decisions, as well as to maintain the health of SCPS. This survey first recalls the concepts of dependability, and proposes a generic environment-in-loop processing flow of self-management CPS, and then analyzes the error sources and challenges of self-management through the formal feedback flow. Focusing on reducing the complexity, we first survey the self-adaptive architecture approaches and applied dependability means, then we introduce a hybrid multi-role self-adaptive architecture, and discuss the supporting technologies for dependable self-management at the architecture level. Focus on dependable environment-centered adaptation, we investigate the verification and validation (V&V) methods for making safe self-adaptation decision and the solutions for processing decision dependably. For system-centered adaptation, the comprehensive self-healing methods are summarized. Finally, we analyze the missing pieces of the technology puzzle and the future directions. In this survey, the technical trends for dependable CPS design and maintenance are discussed, an all-in-one solution is proposed to integrate these technologies and build a dependable organic SCPS. To the best of our knowledge, this is the first comprehensive survey on dependable SCPS building and evaluation.

Adaptation of antibiotic treatment to clinical practice guidelines in patients aged ⩾65 years hospitalised due to community-acquired pneumonia.

Early, conforming antibiotic treatment in elderly patients hospitalised for community-acquired pneumonia (CAP) is a key factor in the prognosis and mortality. The objective was to examine whether empirical antibiotic treatment was conforming according to the Spanish Society of Pulmonology and Thoracic Surgery guidelines in these patients. Multicentre study in patients aged ⩾65 years hospitalised due to CAP in the 2013-14 and 2014-15 influenza seasons. We collected socio-demographic information, comorbidities, influenza/pneumococcal vaccination history and antibiotics administered using a questionnaire and medical records. Bivariate analyses and multilevel logistic regression were made. In total, 1857 hospitalised patients were included, 82 of whom required intensive care unit (ICU) admission. Treatment was conforming in 51.4% (95% confidence interval (CI) 49.1-53.8%) of patients without ICU admission and was associated with absence of renal failure without haemodialysis (odds ratio (OR) 1.49, 95% CI 1.15-1.95) and no cognitive dysfunction (OR 1.71, 95% CI 1.25-2.35), when the effect of the autonomous community was controlled for. In patients with ICU admission, treatment was conforming in 45.1% (95% CI 34.1-56.1%) of patients and was associated with the hospital visits in the last year (<3 vs. ⩾3, OR 2.70, 95% CI 1.03-7.12) and there was some evidence that this was associated with season. Although the reference guidelines are national, wide variability between autonomous communities was found. In patients hospitalised due to CAP, health services should guarantee the administration of antibiotics in a consensual manner that is conforming according to clinical practice guidelines.

Incentivizing Verifiable Privacy-Protection Mechanisms for Offline Crowdsensing Applications.

Incentive mechanisms of crowdsensing have recently been intensively explored. Most of these mechanisms mainly focus on the standard economical goals like truthfulness and utility maximization. However, enormous privacy and security challenges need to be faced directly in real-life environments, such as cost privacies. In this paper, we investigate offline verifiable privacy-protection crowdsensing issues. We firstly present a general verifiable privacy-protection incentive mechanism for the offline homogeneous and heterogeneous sensing job model. In addition, we also propose a more complex verifiable privacy-protection incentive mechanism for the offline submodular sensing job model. The two mechanisms not only explore the private protection issues of users and platform, but also ensure the verifiable correctness of payments between platform and users. Finally, we demonstrate that the two mechanisms satisfy privacy-protection, verifiable correctness of payments and the same revenue as the generic one without privacy protection. Our experiments also validate that the two mechanisms are both scalable and efficient, and applicable for mobile devices in crowdsensing applications based on auctions, where the main incentive for the user is the remuneration.

MQAPsingle: A quasi single-model approach for estimation of the quality of individual protein structure models.

We present a Model Quality Assessment Program (MQAP), called MQAPsingle, for ranking and assessing the absolute global quality of single protein models. MQAPsingle is quasi single-model MQAP, a method that combines advantages of both "pure" single-model MQAPs and clustering MQAPs. This approach results in higher accuracy compared to the state-of-the-art single-model MQAPs. Notably, the prediction for a given model is the same regardless if this model is submitted to our server alone or together with other models. Proteins 2016; 84:1021-1028. © 2015 Wiley Periodicals, Inc.

Comparison of the validity of stroke diagnoses in a medical quality register and an administrative health register.

AIMS: Health registers are essential sources of data used in a wide range of stroke research, including epidemiological, clinical and healthcare studies. Regardless of the type of register, the data must be of high quality to be useful. In this study, we investigated and compared the correctness and completeness of the Norwegian Patient Register (an administrative health register) and the Norwegian Stroke Register (a medical quality register for acute stroke). METHODS: We reviewed the medical records for 5192 admissions to hospital in 2012 and defined cases of stroke in the two registers as true positive, false positive, true negative or false negative. We calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value with 95% confidence intervals assuming a normal approximation of the binomial distribution. RESULTS: The Norwegian Stroke Register was highly correct and relatively complete (sensitivity 88.1%, specificity 100% and PPV 98.6%). The Norwegian Patient Register was more complete, but less correct, when we included both the main and secondary diagnoses of stroke (sensitivity 96.8%, specificity 99.6% and PPV 79.7%); restricting the analyses to the main diagnoses of stroke resulted in less complete and more correct registrations (sensitivity 86.1%, specificity 99.9% and PPV 93.5%). CONCLUSIONS: The Norwegian Stroke Register and the Norwegian Patient Register are adequately complete and correct to serve as valuable sources of data for epidemiological, clinical and healthcare studies, as well as for administrative purposes.

Data extraction from electronic health records (EHRs) for quality measurement of the physical therapy process: comparison between EHR data and survey data.

BACKGROUND: With the emergence of the electronic health records (EHRs) as a pervasive healthcare information technology, new opportunities and challenges for use of clinical data for quality measurements arise with respect to data quality, data availability and comparability. The objective of this study is to test whether data extracted from electronic health records (EHRs) was of comparable quality as survey data for the calculation of quality indicators. METHODS: Data from surveys describing patient cases and filled out by physiotherapists in 2009-2010 were used to calculate scores on eight quality indicators (QIs) to measure the quality of physiotherapy care. In 2011, data was extracted directly from EHRs. The data collection methods were evaluated for comparability. EHR data was compared to survey data on completeness and correctness. RESULTS: Five of the eight QIs could be extracted from the EHRs. Three were omitted from the indicator set, as they proved too difficult to be extracted from the EHRs. Another QI proved incomparable due to errors in the extraction software of some of the EHRs. Three out of four comparable QIs performed better (p < 0.001) in EHR data on completeness. EHR data also proved to be correct; the relative change in indicator scores between EHR and survey data were small (<5 %) in three out of four QIs. CONCLUSION: Data quality of EHRs was sufficient to be used for the calculation of QIs, although comparability to survey data was problematic. Standardization is needed, not only to be able to compare different data collection methods properly, but also to compare between practices with different EHRs. EHRs have the option to administrate narrative data, but natural language processing tools are needed to quantify these text boxes. Such development, can narrow the comparability gap between scoring QIs based on EHR data and based on survey data. EHRs have the potential to provide real time feedback to professionals and quality measurements for research, but more effort is needed to create unambiguous and uniform information and to unlock written text in a standardized manner.

Institutionalized Discontent.

Examining past experiences of student activism at Berkeley this article suggests that the present storm of political correctness sweeping American universities represents more than just another of the periodic crusades that have disrupted academic life over the years. The current wave of activism is different largely because the ever-present minorities of militant faculty and student activists have gained significant reinforcements in their struggle to transform the culture and mission of higher education. Over the last several decades federal regulations and funds have created an alternative bureaucracy within universities that is devoted, not to the core academic mission of teaching and research, but to improving the social climate of university life. The legitimacy and power of the social climate bureaucracy depend on heightening the perception that academic life involves a dangerous environment, from which students need protection - a service provided through creating safe spaces, helping students to recognize micro-aggressions, training them in sexual assault prevention, conducting sensitivity training for faculty and the like. Devoted to heightening this perception of the university campus as a hostile environment, the climate bureaucracy has become a source of institutionalized discontent.

Effect of peer instruction on the likelihood for choosing the correct response to a physiology question.

The aims of the present study were to measure the effects of individual answer (correct vs. incorrect), individual answer of group members (no vs. some vs. all correct), self-confidence about the responses (low vs. mid vs. high), sex (female vs. male students), and group size (2-4 students) on the odds for change and for correctness after peer instruction in a veterinary physiology course (n = 101 students). Data were assessed by multivariable logistic regression analysis. The likelihood for change after peer instruction increased when the confidence on an individual answer was low (P < 0.01), when the answer was incorrect (P < 0.01), and when group members had different responses (P < 0.01). The likelihood for correctness after peer instruction increased when the confidence in group answers was high (P < 0.01), when the individual answer was correct (P < 0.01), and when at least one of the group members had the correct response (P < 0.01). After peer discussion, more changes were from incorrect to correct responses than vice versa (72% vs. 28%, P < 0.01). Changes to correct answers occurred after discussion with peers having both the correct individual response (76% of times) and also the incorrect individual answer (24% of times). In conclusion, the benefits of peer instruction are due to students having correct answers generally prevail in discussions. Also, students who all have incorrect answers can get the correct answer through debate and discussion.

In-Cell Testing of Zinc-Dependent Histone Deacetylase Inhibitors in the Presence of Class-Selective Fluorogenic Substrates: Potential and Limitations of the Method.

The development of anticancer drugs based on zinc-dependent histone deacetylase inhibitors (HDACi) has acquired great practical significance over the past decade. The most important HDACi characteristics are selectivity and strength of inhibition since they determine the mechanisms of therapeutic action. For in-cell testing of the selectivity of de novo-synthesized HDACi, Western blot analysis of the level of acetylation of bona fide protein substrates of HDACs of each class is usually used. However, the high labor intensity of this method prevents its widespread use in inhibitor screening. We developed an in-cell high-throughput screening method based on the use of three subtype-selective fluorogenic substrates of the general structure Boc-Lys(Acyl)-AMC, which in many cases makes it possible to determine the selectivity of HDACi at the class level. However, we found that the additional inhibitory activity of HDACi against metallo-ß-lactamase domain-containing protein 2 (MBLAC2) leads to testing errors.