Tag: nevin manimala

J Glob Health. 2023 Oct 27;13:06050. doi: 10.7189/jogh.13.06050.

ABSTRACT

BACKGROUND: During health emergencies, leading healthcare organisations, such as the World Health Organization (WHO), the European Centre for Disease Control and Prevention (ECDC), and the United States Centers for Disease Control and Prevention (CDC), provide guidance for public health response. Previous studies have evaluated clinical practice guidelines (CPGs) produced in response to epidemics or pandemics, yet few have focused on public health guidelines and recommendations. To address this gap, we assessed health systems guidance (HSG) produced by the WHO, the ECDC, and the CDC for the 2009 H1N1 and COVID-19 pandemics.

METHODS: We extracted HSG for the H1N1 and COVID-19 pandemics from the organisations’ dedicated repositories and websites. After screening the retrieved documents for eligibility, five assessors evaluated them using the Appraisal of Guidelines Research & Evaluation – Health Systems (AGREE-HS) tool to assess the completeness and transparency of reporting according to the five AGREE-HS domains: “Topic”, “Participants”, “Methods”, “Recommendations”, and “Implementability”.

RESULTS: Following the screening process, we included 108 HSG in the analysis. We observed statistically significant differences between the H1N1 and COVID-19 pandemics, with HSG issued during COVID-19 receiving higher AGREE-HS scores. The HSG produced by the CDC had significantly lower overall scores and single-domain scores compared to the WHO and ECDC. However, all HSG scored relatively low, under the median of 40 total points (range = 10-70), indicating incomplete reporting. The HSG produced by all three organisations received a median score <4 (range = 1-7) for the “Participants”, “Methods”, and “Implementability” domains.

CONCLUSIONS: There is still significant progress to be made in the quality and completeness of reporting in HSG issued during pandemics, especially regarding methodological approaches and the composition of the guidance development team. Due to their significant impact and importance for healthcare systems globally, HSG issued during future healthcare crises should adhere to best reporting practices to increase uptake by stakeholders and ensure public trust in healthcare organisations.

PMID:37883198 | DOI:10.7189/jogh.13.06050

J Med Internet Res. 2023 Oct 26;25:e44417. doi: 10.2196/44417.

ABSTRACT

BACKGROUND: Machine learning (ML) methods have shown great potential in predicting colorectal cancer (CRC) survival. However, the ML models introduced thus far have mainly focused on binary outcomes and have not considered the time-to-event nature of this type of modeling.

OBJECTIVE: This study aims to evaluate the performance of ML approaches for modeling time-to-event survival data and develop transparent models for predicting CRC-specific survival.

METHODS: The data set used in this retrospective cohort study contains information on patients who were newly diagnosed with CRC between December 28, 2012, and December 27, 2019, at West China Hospital, Sichuan University. We assessed the performance of 6 representative ML models, including random survival forest (RSF), gradient boosting machine (GBM), DeepSurv, DeepHit, neural net-extended time-dependent Cox (or Cox-Time), and neural multitask logistic regression (N-MTLR) in predicting CRC-specific survival. Multiple imputation by chained equations method was applied to handle missing values in variables. Multivariable analysis and clinical experience were used to select significant features associated with CRC survival. Model performance was evaluated in stratified 5-fold cross-validation repeated 5 times by using the time-dependent concordance index, integrated Brier score, calibration curves, and decision curves. The SHapley Additive exPlanations method was applied to calculate feature importance.

RESULTS: A total of 2157 patients with CRC were included in this study. Among the 6 time-to-event ML models, the DeepHit model exhibited the best discriminative ability (time-dependent concordance index 0.789, 95% CI 0.779-0.799) and the RSF model produced better-calibrated survival estimates (integrated Brier score 0.096, 95% CI 0.094-0.099), but these are not statistically significant. Additionally, the RSF, GBM, DeepSurv, Cox-Time, and N-MTLR models have comparable predictive accuracy to the Cox Proportional Hazards model in terms of discrimination and calibration. The calibration curves showed that all the ML models exhibited good 5-year survival calibration. The decision curves for CRC-specific survival at 5 years showed that all the ML models, especially RSF, had higher net benefits than default strategies of treating all or no patients at a range of clinically reasonable risk thresholds. The SHapley Additive exPlanations method revealed that R0 resection, tumor-node-metastasis staging, and the number of positive lymph nodes were important factors for 5-year CRC-specific survival.

CONCLUSIONS: This study showed the potential of applying time-to-event ML predictive algorithms to help predict CRC-specific survival. The RSF, GBM, Cox-Time, and N-MTLR algorithms could provide nonparametric alternatives to the Cox Proportional Hazards model in estimating the survival probability of patients with CRC. The transparent time-to-event ML models help clinicians to more accurately predict the survival rate for these patients and improve patient outcomes by enabling personalized treatment plans that are informed by explainable ML models.

PMID:37883174 | DOI:10.2196/44417

Elife. 2023 Oct 26;12:e82823. doi: 10.7554/eLife.82823.

ABSTRACT

During perceptual decision-making tasks, centroparietal electroencephalographic (EEG) potentials report an evidence accumulation-to-bound process that is time locked to trial onset. However, decisions in real-world environments are rarely confined to discrete trials; they instead unfold continuously, with accumulation of time-varying evidence being recency-weighted towards its immediate past. The neural mechanisms supporting recency-weighted continuous decision-making remain unclear. Here, we use a novel continuous task design to study how the centroparietal positivity (CPP) adapts to different environments that place different constraints on evidence accumulation. We show that adaptations in evidence weighting to these different environments are reflected in changes in the CPP. The CPP becomes more sensitive to fluctuations in sensory evidence when large shifts in evidence are less frequent, and the potential is primarily sensitive to fluctuations in decision-relevant (not decision-irrelevant) sensory input. A complementary triphasic component over occipito-parietal cortex encodes the sum of recently accumulated sensory evidence, and its magnitude covaries with parameters describing how different individuals integrate sensory evidence over time. A computational model based on leaky evidence accumulation suggests that these findings can be accounted for by a shift in decision threshold between different environments, which is also reflected in the magnitude of pre-decision EEG activity. Our findings reveal how adaptations in EEG responses reflect flexibility in evidence accumulation to the statistics of dynamic sensory environments.

PMID:37883173 | DOI:10.7554/eLife.82823

JMIR Form Res. 2023 Oct 26;7:e49009. doi: 10.2196/49009.

ABSTRACT

BACKGROUND: Web-based sexual health interventions may be more acceptable to people compared with face-to-face support, given the stigma and embarrassment often associated with sexual problems. The Dutch public sexual health clinics (SHCs) conducted an implementation pilot with 4 web-based self-training programs on sexual dysfunctions (WSTPs) for young people. In addition to a basic sexuality program, the WSTPs focused on the following complaints: pain during intercourse, premature ejaculation, and no sex drive.

OBJECTIVE: This study aims to gain insight into the potential reach of the freely offered WSTPs; use, acceptance, evaluation, and perceived impact of the WSTPs by young people; and evaluation and acceptance of the WSTPs by nurses of the SHCs.

METHODS: A quantitative baseline measurement (BM) and a follow-up measurement (FM) were conducted among the users. In addition, qualitative data were gathered through video interviews with a sample of respondents of the FM and nurses of the SHCs to gain more in-depth insights into their assessment of the WSTPs. Participants were recruited via social media, posters, and referrals by nurses of the SHCs. Quantitative data were analyzed using descriptive statistics. Independent 2-tailed t tests and one-way independent ANOVAs were used to compare the scores between subgroups based on background characteristics. Dependent 2-tailed t tests were used to assess the possible changes between BM and FM. The interviews were analyzed using a thematic analysis.

RESULTS: A total of 1028 young people (aged 16-24 y) completed the BM, 666 started with 1 of the WSTPs, and 104 participants completed the FM. In addition, 8 users and 8 nurses were interviewed. Of the participants who completed the BM, 87.74% (902/1028) experienced moderate (411/1028, 39.98%) to high (491/1028, 47.76%) severity of complaints, of which 20.43% (210/1028) had had them for >1 year and 27.82% (286/1028) even for ≥2 years, and 38.91% (400/1028) were dissatisfied with their sex lives. Only 8.75% (90/1028) had sought professional help in the past 2 years. At FM, users rated satisfaction with their sex life more positively than they did at BM, and they experienced less discomfort from their complaints. The overall rating was positive, with a mean report grade of 7.3 (SD 1.45; on a 10-point scale). Anonymity, clear information and explanation, and practical exercises are indicated as strengths of the WSTPs, leading to more understanding and normalization. Nurses appreciate the high quality of information and accessibility of the WSTPs. They consider them as a valuable addition to the consultation hours.

CONCLUSIONS: WSTPs can reach a large number of young people with sexual problems who are less likely to seek professional help. This can result in an improved understanding of their issues, a decrease in complaints, and reduced barriers to communicating with a partner or professional.

PMID:37883172 | DOI:10.2196/49009

Elife. 2023 Oct 26;12:RP87958. doi: 10.7554/eLife.87958.

ABSTRACT

Catalytic signaling outputs of protein kinases are dynamically regulated by an array of structural mechanisms, including allosteric interactions mediated by intrinsically disordered segments flanking the conserved catalytic domain. The doublecortin-like kinases (DCLKs) are a family of microtubule-associated proteins characterized by a flexible C-terminal autoregulatory ‘tail’ segment that varies in length across the various human DCLK isoforms. However, the mechanism whereby these isoform-specific variations contribute to unique modes of autoregulation is not well understood. Here, we employ a combination of statistical sequence analysis, molecular dynamics simulations, and in vitro mutational analysis to define hallmarks of DCLK family evolutionary divergence, including analysis of splice variants within the DCLK1 sub-family, which arise through alternative codon usage and serve to ‘supercharge’ the inhibitory potential of the DCLK1 C-tail. We identify co-conserved motifs that readily distinguish DCLKs from all other calcium calmodulin kinases (CAMKs), and a ‘Swiss Army’ assembly of distinct motifs that tether the C-terminal tail to conserved ATP and substrate-binding regions of the catalytic domain to generate a scaffold for autoregulation through C-tail dynamics. Consistently, deletions and mutations that alter C-terminal tail length or interfere with co-conserved interactions within the catalytic domain alter intrinsic protein stability, nucleotide/inhibitor binding, and catalytic activity, suggesting isoform-specific regulation of activity through alternative splicing. Our studies provide a detailed framework for investigating kinome-wide regulation of catalytic output through cis-regulatory events mediated by intrinsically disordered segments, opening new avenues for the design of mechanistically divergent DCLK1 modulators, stabilizers, or degraders.

PMID:37883155 | DOI:10.7554/eLife.87958

Cryo Letters. 2023 Jul-Aug;44(4):208-218.

ABSTRACT

BACKGROUND: The use of sulfated polysaccharides (PS) in seminal cooling is known to improve seminal quality.

OBJECTIVE: To evaluate the effect of different concentrations of PS, extracted from the macroalgae Gracilaria domigensis as a supplement to the seminal cooling medium of the reophilic fish Prochilodus brevis (common curimatã).

MATERIALS AND METHODS: Five semen pools were diluted in ACP-104 (treatment T1), in BTS® (T2) and in BTS® with different concentrations of PS (0.5 [T3]; 1.0 [T4] and 1.5 [T5]). The samples were cooled for different times (0, 6, 24, 48, 72, 96 and 120 h) and after each hour they were analyzed for: morphology, membrane integrity, DNA integrity and sperm kinetics.

RESULTS: There were no significant differences between the treatments containing different concentrations of sulfated polysaccharides. Regarding the different cooling times, it was possible to observe that after hour 96, there was a reduction in the parameters of sperm kinetics. For DNA integrity there was no significant difference in relation to the treatments nor in relation to the hours. For membrane integrity, a reduction was noted as of hour 96, but there was no influence of polysaccharides. For the sperm morphology, there was no statistical difference between the hours, however the BTS was better than the ACP-104.

CONCLUSION: It is concluded that the use of polysaccharides in seminal cooling has no negative effect on sperm parameters and proves that seminal cooling keeps the material viable for up to 72 hours. Doi: 10.54680/fr23410110512.

PMID:37883138

ACS Appl Mater Interfaces. 2023 Oct 26. doi: 10.1021/acsami.3c12489. Online ahead of print.

ABSTRACT

Viologens are fascinating redox-active organic compounds that have been widely explored in electrochromic devices (ECDs). However, the combination of electrochromic and resistive random-access memory in a single viologen remains unexplored. We report the coexistence of bistate electrochromic and single-resistor (1R) memory functions in a novel viologen. A high-performance electrochromic function is achieved by combining viologen (BzV²⁺2PF₆) with polythiophene (P3HT), enabling a “push-pull” electronic effect due to the efficient intermolecular charge transfer in response to an applied bias. The ECDs show high coloration efficiency (ca. 1150 ± 10 cm² C^-1), subsecond switching time, good cycle stability (>10³ switching cycles), and low-bias operation (±1.5 V). The ECDs require low power for switching the color states (55 μW cm^-2 for magenta and 141 μW cm^-2 for blue color). The random-access memory devices (p⁺²-Si/BzV²⁺2PF₆/Al) exhibit distinct low and high resistive states with an ON/OFF ratio of ∼10³, bipolar and nonvolatile characteristics that manifest good performances, and “Write”-“Read”-“Erase” (WRE) functions. The charge conduction mechanism of the RRAM device is elucidated by the Poole-Frenkel model where SET and RESET states arise at a low transition voltage (V_T = ±1.7 V). Device statistics and performance parameters for both electrochromic and memory devices are compared with the literature data. Our findings on electrochromism and nonvolatile memory originated in the same viologen could boost the development of multifunctional, smart, wearable, flexible, and low-cost optoelectronic devices.

PMID:37883131 | DOI:10.1021/acsami.3c12489

J Clin Ultrasound. 2023 Oct 26. doi: 10.1002/jcu.23593. Online ahead of print.

ABSTRACT

PURPOSE: To determine the effects of gestational diabetes mellitus (GDM) on fetal frontal lobe development.

METHODS: This study was conducted prospectively between May 2023 and August 2023 in Ankara City Hospital perinatology clinic. Maternal age, maternal body mass index (BMI), gestational week (GW), biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femur length (FL), estimated fetal weight (EFW), frontal antero-posterior diameter (FAPD), occipito-frontal diameter (OFD), FAPD/OFD ratio, and FAPD/HC ratio, were compared between GDM (n = 40) and low risk controls (n = 56).

RESULTS: The mean maternal age was found higher in the GDM group compared to control group (p = 0.002). Maternal BMI was significantly higher in the GDM group than the control group (p = 0.01). Abdominal circumference (AC) was significantly higher in the GDM group compared to control group (p = 0.04). EFW was significantly higher in the GDM group compared to control group (p = 0.04). FAPD/OFD ratio was found to be higher in the GDM group than in the control group (p = 0.001). Among GDM patients, no statistically significant difference was found in the ultrasound measurements between the groups receiving insulin treatment and those without treatment. According to the correlation analysis results a moderate, positive, and statistically significant correlation was present between FAPD/OFD and GDM. In perinatal outcomes, the rate of neonatal intensive care unit admission was significantly higher in the GDM group.

DISCUSSION: Fetal frontal lobe development seems to be affected by GDM.

PMID:37883124 | DOI:10.1002/jcu.23593

PM R. 2023 Oct 26. doi: 10.1002/pmrj.13093. Online ahead of print.

ABSTRACT

INTRODUCTION: Physical medicine and rehabilitation (PM&R) physicians are trained to perform interventional procedures using local anesthetics (LAs) to reduce pain and enhance function and quality of life. Local anesthetic administration is not benign and one potential complication is Local Anesthetic Systemic Toxicity (LAST). Anesthesiologists also perform interventions with LAs, however, training on LAST may differ between medical specialties.

OBJECTIVE: To investigate if a gap exists between physiatry and anesthesiology physicians’ knowledge of LAST.

DESIGN: Prospective cross-sectional survey study.

SETTING AND PARTICIPANTS: All residents, fellows, and attendings of the anesthesiology and PM&R departments at a single academic medical center.

OUTCOME MEASURE: Primary outcome measures include participants’ self-reported exposure to LAST education and comfort with their LAST knowledge as recorded on a Likert scale, as well as percentage of correctly answered knowledge-based questions on the topic.

RESULTS: Fifty-eight physicians including 28 PM&R and 30 anesthesiology physicians (24 attending and 34 trainees) participated. Anesthesiology trainees and attendings exhibited greater overall perceived knowledge of LAST (trainees U=43, p<.001; attendings U=9, p<.001), with greater exposure to LAST education (trainees U=16.5, p<.001; attendings U=12, p<.001). Assessment of responses to knowledge-based questions on LAST revealed a statistically significant knowledge gap between PM&R and Anesthesia trainees (t=6.62, p= <.001) as well as between attending groups (t=3.25, p= <.01).

CONCLUSION: This study reveals a distinction in both the subjective and objective knowledge of LAST between PM&R and anesthesiology physicians at a single academic institution. This suggests there is opportunity for further assessment of the education on LAST amongst physiatrists and residents in training. This article is protected by copyright. All rights reserved.

PMID:37883117 | DOI:10.1002/pmrj.13093

Invest Ophthalmol Vis Sci. 2023 Oct 3;64(13):43. doi: 10.1167/iovs.64.13.43.

ABSTRACT

PURPOSE: This study aimed to establish an image-based classification that can reveal the clinical characteristics of patients with dry eye using unsupervised learning methods.

METHODS: In this study, we analyzed 82,236 meibography images from 20,559 subjects. Using the SimCLR neural network, the images were categorized. Data for each patient were averaged and subjected to mini-batch k-means clustering, and validated through consensus clustering. Statistical metrics determined optimal category numbers. Using a UNet model, images were segmented to identify meibomian gland (MG) areas. Clinical features were assessed, including tear breakup time (BUT), tear meniscus height (TMH), and gland atrophy. A thorough ocular surface evaluation was conducted on 280 cooperative patients.

RESULTS: SimCLR neural network achieved clustering patients with dry eye into six image-based subtypes. Patients in different subtypes harbored significantly different noninvasive BUT, significantly correlated with TMH. Subtypes 1 and 5 had the most severe MG atrophy. Subtype 2 had the highest corneal fluorescent staining (CFS). Subtype 4 had the lowest TMH, whereas subtype 5 had the highest. Subtypes 3 and 6 had the largest MG areas, and the upper MG areas of a person’s bilateral eyes were highly correlated. Image-based subtypes are related to meibum quality, CFS, and morphological characteristics of MG.

CONCLUSIONS: In this study, we developed an unsupervised neural network model to cluster patients with dry eye into image-based subtypes using meibography images. We annotated these subtypes with functional and morphological clinical characteristics.

PMID:37883092 | DOI:10.1167/iovs.64.13.43