A Threshold QuickDASH Score for Estimating a Diagnosis of Major Depression in Patients With Fingertip Injuries in the American and Dutch Population

Background: The aim was to determine the threshold Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score that estimates a diagnosis of major depression in patients with fingertip injuries in American and Dutch patients. Methods: In this observational cross-sectional study, 112 patients with a recent fingertip injury measured symptoms of depression with the Patient Health Questionnaire and upper extremity disability with the QuickDASH. Results: In the US cohort, 8 of 56 patients had an estimated diagnosis of major depression. A threshold value of QuickDASH of 50 showed a sensitivity of 88% and a specificity of 81%, with a negative predicting value (NPV) of 95% for an estimated diagnosis of major depression. In the Dutch cohort, 7 of 56 patients had an estimated diagnosis of major depression. The same threshold score of 50 had a sensitivity of 71%, a specificity of 63%, and an NPV of 94%. Conclusions: We have found a correlation between experienced loss of function and an estimated diagnosis of major depression in patients with a fingertip injury. Referral to the primary care physician for further evaluation of depression in these patients is advised.

In Silico Modeling and Scoring of PROTAC-Mediated Ternary Complex Poses

Proteolysis targeting chimeras (PROTACs) are bifunctional molecules that can induce the ubiquitination of targeted proteins via the formation of ternary complexes between an E3 ubiquitin ligase and a target protein. The poly-ubiquitinated target protein will be escorted to the proteasome for degradation. Rational design of PROTACs require knowledge of an accurate configuration of the PROTAC induced ternary complex. This study demonstrates that native ternary poses can be distinguished by scoring candidate poses based on the pose residence time. The scoring is essentially heat-and-dissociate trials of candidate poses sampled by MD and pre-ranked by the classic MM/GBSA method. It is practical, simple to use and self-intuitive, relying on the observation that the assumed more stable native crystal ternary poses maintained a longer residence time than non-native ones at both room and higher temperatures. A time score and temperature score were generated from multiple replicate trajectories. These scores were able to correctly identify the native pose from non-native ones in all the systems examined. The absolute numbers were comparable across different systems in all currently available VHL and CRBN-containing ternary crystal structures. Therefore, it is also possible to provide an empirical criteria for unresolved ternary structures that under the conditions of this study. If a ternary pose is stable up to over a certain threshold score, it is likely a native pose. The success of the method is in part attributed to the dynamic nature of the pose change analysis which naturally involves entropic effects, one that is intrinsically unavailable with faster static scoring methods that consider molecular mechanical energy only. Protein-protein binding entropy is much more significant than in protein-ligands binding. The success is also attributed to the fact that the protein structures themselves were all stable in the short heating trials.

In Silico Modeling and Scoring of PROTAC-Mediated Ternary Complex Poses

Proteolysis targeting chimeras (PROTACs) are bifunctional molecules that can induce the ubiquitination of targeted proteins via the formation of ternary complexes between an E3 ubiquitin ligase and a target protein. The poly-ubiquitinated target protein will be escorted to the proteasome for degradation. Rational design of PROTACs require knowledge of an accurate configuration of the PROTAC induced ternary complex. This study demonstrates that native ternary poses can be distinguished by scoring candidate poses based on the pose residence time. The scoring is essentially heat-and-dissociate trials of candidate poses sampled by MD and pre-ranked by the classic MM/GBSA method. It is practical, simple to use and self-intuitive, relying on the observation that the assumed more stable native crystal ternary poses maintained a longer residence time than non-native ones at both room and higher temperatures. A time score and temperature score were generated from multiple replicate trajectories. These scores were able to correctly identify the native pose from non-native ones in all the systems examined. The absolute numbers were comparable across different systems in all currently available VHL and CRBN-containing ternary crystal structures. Therefore, it is also possible to provide an empirical criteria for unresolved ternary structures that under the conditions of this study. If a ternary pose is stable up to over a certain threshold score, it is likely a native pose. The success of the method is in part attributed to the dynamic nature of the pose change analysis which naturally involves entropic effects, one that is intrinsically unavailable with faster static scoring methods that consider molecular mechanical energy only. Protein-protein binding entropy is much more significant than in protein-ligands binding. The success is also attributed to the fact that the protein structures themselves were all stable in the short heating trials.

Evaluating the performance of ACR, SLICC and EULAR/ACR classification criteria in childhood onset systemic lupus erythematosus

Background The ACR 1997, SLICC 2012 and EULAR/ACR 2019 classification criteria were validated based on adult patients. To date, there are no classification criteria specific for children with SLE. The aim of the study is to compare the performance characteristics among the three SLE classification criteria (ACR-1997, SLICC-2012 and EULAR/ACR-2019) in childhood onset SLE (cSLE) cohort of Arab ethnicity from Oman. Methods We conducted a retrospective multicenter study in Oman of cSLE patients as cases and patients with other rheumatic disease with a positive ANA titer as controls. The cSLE cases recruited were children diagnosed with SLE before 13 years of age. Data was retrospectively collected to establish the ACR-1997, SLICC-2012 and EULAR/ACR-2019 criteria fulfilled at first visit, first year follow up and last follow up. Results Study population included 113 cSLE cases (mean age at diagnosis of 7.3 ± 3.4 years with disease duration of 6.1 ± 4.6 years) and 51 controls (mean age at diagnosis 5.0 ± 3.4 with disease duration 5.7 ± 3.9). The cSLE cases had higher frequency of familial SLE than controls (38% vs 7.8%; p < 0.001). The performance measures demonstrated that EULAR/ACR-2019 criteria had the highest sensitivity (81, 88, 89%) compared to ACR 1997 (49, 57, 66%) and SLICC 2012 (76, 84,86%); while the ACR 1997 had the highest specificity (96%) compared to SLICC 2012 (94%) and EULAR/ACR 2019 (90%) at first visit, first year and last assessment. When we increased the threshold score to ≥13 rather than the traditional score ≥ 10 for ACR/EULAR 2019, there was increased specificity (96%) at the expense of lower sensitivity (76, 83, and 84%) at first visit, first year and last assessment. Conclusion In this cSLE population, EULAR/ACR 2019 scored better at initial presentation, first year and last assessment follow up. Further multinational studies are needed to validate the appropriate cut off score for the newly proposed ACR/EULAR 2019 classification criteria in cSLE to increase early sensitivity and specificity for cSLE classification.

Anxiety, depression, and glycemic control during Covid-19 pandemic in youths with type 1 diabetes

Objectives Our study aims to assess the impact of lockdown during the coronavirus disease 2019 pandemic on glycemic control and psychological well-being in youths with type 1 diabetes. Methods We compared glycemic metrics during lockdown with the same period of 2019. The psychological impact was evaluated with the Test of Anxiety and Depression. Results We analyzed metrics of 117 adolescents (87% on Multiple Daily Injections and 100% were flash glucose monitoring/continuous glucose monitoring users). During the lockdown, we observed an increase of the percentage of time in range (TIR) (p<0.001), with a significant reduction of time in moderate (p=0.002), and severe hypoglycemia (p=0.001), as well as the percentage of time in hyperglycemia (p<0.001). Glucose variability did not differ (p=0.863). The glucose management indicator was lower (p=0.001). 7% of youths reached the threshold-score (≥115) for anxiety and 16% for depression. A higher score was associated with lower TIR [p=0.028, p=0.012]. Conclusions Glycemic control improved during the first lockdown period with respect to the previous year. Symptoms of depression and anxiety were associated with worse glycemic control; future researches are necessary to establish if this improvement is transient and if psychological difficulties will increase during the prolonged pandemic situation.

Validation of an obstructive sleep apnea symptom inventory in persons with multiple sclerosis

Background: Improved screening for obstructive sleep apnea (OSA) could enhance multiple sclerosis (MS) clinical care; yet the utility of current screening tools for OSA have yet to be evaluated in persons with multiple sclerosis (PwMS). Objectives: The STOP-Bang Questionnnaire is an 8-item screening tool for OSA that is commonly used in non-MS samples. The aim of this study was to assess the validity of the STOP-Bang in PwMS. Methods: STOP-Bang and polysomnography data were analyzed from n = 200 PwMS. Sensitivity, specificity, positive-, and negative-predictive value (PPV and NPV) were calculated, with receiving operating characteristic (ROC) curves, for each STOP-Bang threshold score, against polysomnography-confirmed OSA diagnosis at three apnea severity thresholds (mild, moderate, and severe). Results: Nearly 70% had a STOP-Bang score of ⩾3% and 78% had OSA. The STOP-Bang at a threshold score of 3 provided sensitivities of 87% and 91% to detect moderate and severe OSA, respectively; and NPV of 84% and 95% to identify PwMS without moderate or severe OSA, respectively. Sensitivity to detect milder forms of OSA was 76%. The NPV to identify persons without milder forms of OSA was 40%. Conclusion: The STOP-Bang Questionnaire is an effective tool to screen for moderate and severe OSA in PwMS, but may be insufficient to exclude mild OSA.

The Level of Religion Radicalism Understanding Among University Students in Banyumas Region

Students as the nation’s next-generation and the academic community should have a global understanding of religious radicalism danger. However, recently, many national mass media have reported about the radical ideological infiltration targeting university students. The understanding level of religious radicalism among university students can be a consideration in mapping the potential for the spread of radical ideology. However, there are indications that many students understand religious radicalism. This study aims to determine and analyse the level of understanding of re- religious radicalism among university students in the Banyumas region. Research respondents totalled 350 people from four universities in the Banyumas region. The data collection method was through a closed questionnaire. The basis of the composition of the questionnaire question items is Bloom’s Taxonomy levels C1 and C2. The correct answer point is four, and the wrong answer is 0. The researcher divided the respondents’ understanding level into three categories: high, medium, and low. The results showed that understanding religious radicalism in students studying exact sciences was 67.54%. The understanding stage of religious radicalism in students studying social science was in the range of 67.89%. University students in the Banyumas region have an average of 67.71% or are in the medium category with a low threshold score.

Evaluating the Performance of ACR, SLICC and EULAR/ACR Classification Criteria in Childhood onset Systemic Lupus Erythematosus

Background: The ACR 1997, SLICC 2012 and EULAR/ACR 2019 classification criteria were validated based on adult patients. To date, there are no classification criteria specific for children with SLE. The aim of the study is to compare the performance characteristics among the three SLE classification criterias (ACR-1997, SLICC-2012 and EULAR/ACR-2019) in childhood onset SLE (cSLE) cohort of Arab ethnicity from Oman. Methods: We conducted a retrospective multicenter study of cSLE patients as cases and patients with other rheumatic disease with a positive ANA titer as controls. Data were retrospectively collected to establish the ACR-1997, SLICC-2012 and EULAR/ACR-2019 criteria fulfilled at first visit, first year follow up and last follow up. Results: Study population included 113 cSLE cases (mean age at diagnosis 7.3 ± 3.4 years with disease duration 6.1 ± 4.6 years) and 51 controls (mean age at diagnosis 5.0 ± 3.4 with disease duration 5.7 ± 3.9). The performance measures demonstrated that EULAR/ACR-2019 criteria had the highest sensitivity (81%, 88%, 89%) compared to ACR 1997 ( 49%, 57%, 66%) and SLICC 2012 (76%, 84%,86%); while the ACR 1997 had the highest specificity (96%) compared to SLICC 2012 (94%) and EULAR/ACR 2019 ( 90%) at first visit, first year and last assessment. When we increased the threshold score to ≥ 13 rather than the traditional score ≥ 10 for ACR/EULAR 2019, there was increased specificity (96%) at the expense of lower sensitivity (76%, 83%, and 84%) at first visit, first year and last assessment. Conclusion: In this cSLE population, EULAR/ACR 2019 scored better at initial presentation, first year and last assessment follow up. Further multinational studies are needed to validate the appropriate cut off score for the newly proposed ACR/EULAR 2019 classification criteria in cSLE to increase early sensitivity and specificity for cSLE classification.

Methodology for seismic risk screening of existing buildings in Canada: Non-structural component scoring system

The National Research Council of Canada (NRC) has recently developed a Semi-Quantitative Seismic Risk Screening Tool (SQST) to supersede the 1993 NRC Manual for Screening of Buildings for Seismic Investigation. The proposed screening tool incorporates a methodology for estimating global seismic risk of existing buildings associated with failure of their non-structural components. The methodology assesses global seismic risk using a qualitative yet comprehensive scoring system. The scoring system consists of a global non-structural component score and acceptable threshold scores. The global score is based on the most critical components. It combines a basic score with score modifiers for key parameters affecting the seismic response of non-structural components. The acceptable threshold score is based on the building’s consequence of failure, the building’s importance category, and the component factor. The scoring system is calibrated to be consistent with the seismic risk acceptance criteria previously developed for preliminary seismic risk screening of existing buildings, based on Canadian seismicity, building age, remaining occupancy time, and consequences of failure.

Critical Role of General Practitioners in Preventing Readmission Following Emergency Department Alcohol Screening and Brief Intervention Management of Alcohol-Related Problems

Introduction/Objectives: Alcohol screening and brief intervention (ASBI) strategies are useful in general practice (GP) but their effectiveness in the emergency department (ED) is unclear. We evaluated the effect of ED-based ASBI on re-admissions. Methods: 453 ED subjects exceeding the threshold score on the three-item Alcohol Use Disorders Identification Test-Consumption (females 3+: males 4+) were randomized. We conducted telephone follow-up at 1 and 3 months and recorded hospital events 6 months pre- and post-enrolment. Results: Median weekly alcohol use was 20 standard drinks (interquartile range (IQR) 9-45) on enrolment. After 3 months, 247 (55%) were able to be re-interviewed. Median alcohol use was 10 drinks (IQR 4-26). Six months later, subjects receiving ED-ASBI without GP follow-up had significantly greater risk of re-admission compared with those having GP follow-up (OR 1.68, 95%CI 1.06-2.65; P = .028). Conclusions: ASBI reduces the likelihood of ED re-presentation only in subjects who have GP follow-up. The study has been registered as a clinical trial (Australian and New Zealand Clinical Trial Registry ACTRN12617001254381).