Nevin Manimala

Biomed Tech (Berl). 2024 Mar 8. doi: 10.1515/bmt-2024-0060. Online ahead of print.

ABSTRACT

OBJECTIVES: Diagnosing the sleep apnea can be critical in preventing the person having sleep disorder from unhealthy results. The aim of this study is to obtain a sleep apnea scoring approach by comparing parametric and non-parametric power spectral density (PSD) estimation methods from EEG signals recorded from different brain regions (C4-M1 and O2-M1) for transient signal analysis of sleep apnea patients.

METHODS: Power Spectral Density (PSD) methods (Burg, Yule-Walker, periodogram, Welch and multi-taper) are examined for the detection of apnea transition states including pre-apnea, intra-apnea and post-apnea together with statistical methods.

RESULTS: In the experimental studies, EEG recordings available in the database were analyzed with PSD methods. Results showed that there are statistically significant differences between parametric and non-parametric methods applied for PSD analysis of apnea transition states in delta, theta, alpha and beta bands. Moreover, it was also revealed that PSD of EEG signals obtained from C4-M1 and O2-M1 channels were also found statistically different as proved by classification using the K-nearest neighbour (KNN) method.

CONCLUSIONS: It was concluded that not only applying different PSD methods, but also EEG signals from different brain regions provided different statistical results in terms of apnea transition states as obtained from KNN classification.

PMID:38452359 | DOI:10.1515/bmt-2024-0060

Bioinformatics. 2024 Mar 7:btae142. doi: 10.1093/bioinformatics/btae142. Online ahead of print.

ABSTRACT

MOTIVATION: Anticancer peptides (ACPs) have natural cationic properties and can act on the anionic cell membrane of cancer cells to kill cancer cells. Therefore, ACPs have become a potential anticancer drug with good research value and prospect.

RESULTS: In this paper, we propose AACFlow, an end-to-end model for identification of ACPs based on deep learning. End-to-end models have more room to automatically adjust according to the data, making the overall fit better and reducing error propagation. The combination of attention augmented convolutional neural network (AAConv) and multi-layer convolutional neural network (CNN) forms a deep representation learning module, which is used to obtain global and local information on the sequence. Based on the concept of flow network, multi-head flow-attention mechanism is introduced to mine the deep features of the sequence to improve the efficiency of the model. On the independent test dataset, the ACC, Sn, Sp, and AUC values of AACFlow are 83.9%, 83.0%, 84.8%, and 0.892, respectively, which are 4.9%, 1.5%, 8.0%, and 0.016 higher than those of the baseline model. The MCC value is 67.85%. In addition, we visualize the features extracted by each module to enhance the interpretability of the model. Various experiments show that our model is more competitive in predicting ACPs.

AVAILABILITY: The codes and datasets are accessible at https://github.com/z11code/AACFlow.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:38452348 | DOI:10.1093/bioinformatics/btae142

Anal Chem. 2024 Mar 7. doi: 10.1021/acs.analchem.3c02958. Online ahead of print.

ABSTRACT

Microorganisms are important sources of bioactive natural products. However, the complexity of microbial metabolites and the low abundance of active compounds render the isolation and purification process laborious and inefficient. During our search for active substances capable of inhibiting the newly discovered highly lethal Vibrio strain vp-HL, we found that the fermentation broth of multiple Bacillus strains exhibited antibacterial activity. However, the substances responsible for the activity remained unclear. Metabolomics, molecular networking (MN), and the Structural similarity Network Annotation Platform for Mass Spectrometry (SNAP-MS) were employed in conjunction with bioactivity screening to predict the antibacterial compounds from Bacillus strains. The analysis of fractions, and their isolation, NMR-based annotation, and bioactivity evaluation of an amicoumacin compound partially confirmed the prediction from these statistical analyses. This work presents the potential of marine Bacillus in producing active substances against Vibrio species. Additionally, it highlighted the significance and feasibility of metabolomics and MN in the dereplication of compounds and the determination of isolation targets.

PMID:38452345 | DOI:10.1021/acs.analchem.3c02958

Telemed J E Health. 2024 Mar 7. doi: 10.1089/tmj.2023.0554. Online ahead of print.

ABSTRACT

Background: The COVID-19 pandemic significantly increased telehealth adoption. Rural communities experience challenges relating to telehealth, including a shortage of clinicians, low health literacy, mistrust of medicine, and limited technology access, yet rural perceptions have not been a subject of robust study. The setting of this study was a rural Midwestern family medicine clinic within an academic health system. Methods: Surveys were given to all patients of age 18 or older visiting the clinic over a one-week period. Those who expressed interest were contacted for a semistructured interview. Descriptive statistics and chi-square testing were used to analyze survey results for significant relationships, while interview transcripts were analyzed for themes. Results: Of respondents, 27% indicated prior telehealth use and were more likely to prefer telehealth visits (p = 0.03). Perceptions of telehealth were sorted into themes, including scope of care, convenience, and technology. Telehealth was preferred for discussing test results or mental health. Barriers such as travel time and transportation access favored telehealth. Although more convenient, telehealth was found to be less effective for relationship building. The absence of physical examination during phone visits was a concern. Phone visits were more prevalent due to failure of video-based technology. Conclusions: Despite the potential to address these unique challenges in rural communities, telehealth acceptance is poor. Barriers such as accessibility of technology can be improved through governmental and health systemwide measures. Future work can help develop interventions that counter negative perceptions of telehealth while increasing interest and uptake in rural communities.

PMID:38452338 | DOI:10.1089/tmj.2023.0554

J Clin Oncol. 2024 Mar 7:JCO2302182. doi: 10.1200/JCO.23.02182. Online ahead of print.

ABSTRACT

PURPOSE: The US Food and Drug Administration (FDA) approved talazoparib with enzalutamide for first-line treatment of patients with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC).

PATIENTS AND METHODS: The approval was based on the HRR gene-mutated (HRRm) population of TALAPRO-2, a randomized, double-blind trial that randomly assigned 1,035 patients with mCRPC to receive enzalutamide with either talazoparib or placebo. Two cohorts enrolled sequentially: an all-comer population (Cohort 1), followed by an HRRm-only population (Cohort 2). The independent primary end points were radiographic progression-free survival (rPFS) per blinded independent central review (BICR) in Cohort 1 (all-comers) and in the combined HRRm population (all HRRm patients from Cohorts 1 and 2). Overall survival (OS) was a key secondary end point.

RESULTS: A statistically significant improvement in rPFS by BICR was demonstrated in both the all-comers cohort and the combined HRRm population, with hazard ratio (HR) of 0.63 (95% CI, 0.51 to 0.78; P < .0001) and 0.45 (95% CI, 0.33 to 0.61; P < .0001), respectively. In an exploratory analysis of the 155 patients with BRCA-mutated (BRCAm) mCRPC, rPFS HR was 0.20 (95% CI, 0.11 to 0.36). In the non-HRRm/unknown stratum of Cohort 1 (n = 636), the rPFS HR was 0.70 (95% CI, 0.54 to 0.89). OS was immature.

CONCLUSION: Despite a statistically significant rPFS improvement in the all-comer cohort, FDA did not consider the magnitude of rPFS clinically meaningful in the context of the broad indication, combination treatment, and safety profile. Approval was therefore limited to patients with HRRm mCRPC, for whom there was a statistically significant and clinically meaningful improvement in rPFS and favorable OS results. This represents the first approval for the first-line treatment of patients with HRRm mCRPC.

PMID:38452327 | DOI:10.1200/JCO.23.02182

Psychiatr Pol. 2023 Oct 16:1-22. doi: 10.12740/PP/OnlineFirst/169912. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to investigate incidences of stigmatisation and discrimination by selected health professionals against patients with HIV/AIDS and HCV, and to assess how these affected feelings in both groups.

METHODS: The study involved 160 patients – 80 diagnosed with HIV/AIDS in the baseline group and 80 with HCV in the comparison group. Patients were recruited from among patients treated in two outpatient clinics of the University Hospital in Krakow.

RESULTS: Incidents of stigmatisation and discrimination were observed significantly more often in the HIV/AIDS group compared to the HCV group. According to the patients, incidents of stigmatisation and discrimination on the part of medical staff occur due to fear and a sense of threat from infection with the viruses. The experience of stigmatisation and discrimination by patients manifests itself in the impediment or denial of healthcare services by medical professionals. Some of the medical staff blamed the patients for the infection, expressed disrespect and verbal aggression towards them, and treated them worse when they found out about the infection. Their emotional state depended on the nature of the relationship with the medical staff triggered by stigmatisation and discrimination.

CONCLUSIONS: Stigmatisation and discrimination by medical staff against patients were, according to the respondents, linked to fear of infection but confirmation of this relationship would require further research. In the course of these cases, patients experienced pejorative verbal evaluation, impediment or denial of health services, which could have specific health consequences. These types of attitudes had a negative impact on their emotional state.

PMID:38452318 | DOI:10.12740/PP/OnlineFirst/169912

Rheumatology (Oxford). 2024 Mar 7:keae140. doi: 10.1093/rheumatology/keae140. Online ahead of print.

ABSTRACT

OBJECTIVES: To investigate cancer risk in rheumatoid arthritis (RA) patients treated with tocilizumab/sarilumab, abatacept, or rituximab compared with those who received tumour necrosis factor inhibitors (TNFi) and compared with biological disease-modifying anti-rheumatic drugs (bDMARD) naïve RA patients.

METHODS: Nationwide registry-based cohort study of RA patients initiating treatment with tocilizumab/sarilumab, abatacept, rituximab, TNFi, and bDMARD-naive patients their second type of conventional synthetic DMARD (csDMARD). Patients were identified in DANBIO and followed for cancer from 2006-2020. Patients could contribute multiple treatments, with person years (PYRS), deaths, and cancers allocated to each treatment group in a ‘latest type of treatment’ manner. Inverse probability of treatment weighting and weighted cause-specific Cox models were used to calculate hazard ratios (HRs) for cancer in each tocilizumab/sarilumab, abatacept, and rituximab group compared with TNFI and bDMARD naïve groups, respectively.

RESULTS: In total, 21 982 treatment initiations, 96 475 PYRS, and 1423 cancers were identified. There were no statistically significant increased HRs for overall cancer in tocilizumab/sarilumab, abatacept, or rituximab treatment groups (HRs ranged from 0.7-1.1). More than five years of abatacept exposure showed a non-significantly increased HR compared with TNFi (HR 1.41, 95% confidence intervals CI 0.74-2.71). For hematological cancers, rituximab treatment showed non-significantly reduced HRs: vs TNFi (HR 0.09; 95%CI 0.00-2.06) and bDMARD-naïve (HR 0.13; 95%CI 0.00-1.89).

CONCLUSION: Treatment with tocilizumab/sarilumab, abatacept, or rituximab in RA patients was not associated with increased risks of cancer compared with TNFi-treated and with bDMARD-naïve RA patients in a real-world setting.

PMID:38452297 | DOI:10.1093/rheumatology/keae140

J Am Med Inform Assoc. 2024 Mar 7:ocae004. doi: 10.1093/jamia/ocae004. Online ahead of print.

ABSTRACT

OBJECTIVE: The timely initiation of renal replacement therapy (RRT) for acute kidney injury (AKI) requires sequential decision-making tailored to individuals’ evolving characteristics. To learn and validate optimal strategies for RRT initiation, we used reinforcement learning on clinical data from routine care and randomized controlled trials.

MATERIALS AND METHODS: We used the MIMIC-III database for development and AKIKI trials for validation. Participants were adult ICU patients with severe AKI receiving mechanical ventilation or catecholamine infusion. We used a doubly robust estimator to learn when to start RRT after the occurrence of severe AKI for three days in a row. We developed a “crude strategy” maximizing the population-level hospital-free days at day 60 (HFD60) and a “stringent strategy” recommending RRT when there is significant evidence of benefit for an individual. For validation, we evaluated the causal effects of implementing our learned strategies versus following current best practices on HFD60.

RESULTS: We included 3748 patients in the development set and 1068 in the validation set. Through external validation, the crude and stringent strategies yielded an average difference of 13.7 [95% CI -5.3 to 35.7] and 14.9 [95% CI -3.2 to 39.2] HFD60, respectively, compared to current best practices. The stringent strategy led to initiating RRT within 3 days in 14% of patients versus 38% under best practices.

DISCUSSION: Implementing our strategies could improve the average number of days that ICU patients spend alive and outside the hospital while sparing RRT for many.

CONCLUSION: We developed and validated a practical and interpretable dynamic decision support system for RRT initiation in the ICU.

PMID:38452293 | DOI:10.1093/jamia/ocae004

Harv Rev Psychiatry. 2024 Mar-Apr 01;32(2):58-62. doi: 10.1097/HRP.0000000000000392.

ABSTRACT

Since the inclusion of gender identity disorder in the third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III), psychiatry and the broader medical field have made substantial alterations in their recognition of and respect for transgender and gender diverse (TGD) identities. As this recognition continues to expand, psychiatrists should be aware of both historical harm and current best care practices, especially in light of psychiatric morbidity in TGD populations relative to the general population. This article contextualizes the history of psychiatry’s engagement with TGD patients and presents the gender minority stress and resilience model to frame the mental health disparities experienced by TGD people. We envision a role for psychiatry that goes beyond gatekeeping gender-affirming hormone therapy and surgeries. Instead, we should invest in equitable care across the continuum of mental health needs. We provide an overview of existing literature to help characterize psychiatric epidemiology for this population, with the goal of offering guidance on how psychiatrists can deliver responsive and high-quality care for TGD people. Some key areas of proposed clinical improvement include culturally tailoring interventions for substance use disorders, reducing medical trauma in acute psychiatric care settings, and better understanding the interplay of psychopharmacology and gender-affirming hormone therapy.

PMID:38452285 | DOI:10.1097/HRP.0000000000000392

J Evol Biol. 2024 Mar 7:voae025. doi: 10.1093/jeb/voae025. Online ahead of print.

ABSTRACT

Members of the genus Clivia show considerable variation in flower pigmentation and morphology. Such variation is effected by mutations that emerge in candidate flower development genes over time. Besides population history, mutations can further illuminate the effects of demographic events in populations in addition to population genetic parameters including selection, recombination, and linkage disequilibrium (LD). The current study aimed to find sequence variants in two anthocyanin biosynthetic genes (DFR and bHLH) of Clivia miniata and use the data to assess population genetic factors from a random collection of orange/red- and yellow-flowered specimens. Overall, average nucleotide diversity in the two anthocyanin genes was moderate (π = 0.00646), whereas haplotypes differed significantly (Hd ≥ 0.9). Gene evolution was seemingly driven by mutations (CmiDFR) or recombination (CmibHLH001). LD decayed swiftly within the analyzed gene regions and supported the feasibility of assessing trait-variant associations via the association/linkage mapping approach. In the end, most associations were found to be spurious, but one haplotype in CmibHLH001 showed a promising correlation to the orange/red flower phenotype in Clivia specimens. In all, the present study is the first to measure gene-level diversity in C. miniata – data that had never been reported so far. Further, the study also identified allelic and haplotypic variants that may be beneficial in future association genetic studies of Clivia. Such studies, however, consider large diverse populations to control for statistical bias intrinsic to the analysis of small datasets.

PMID:38452247 | DOI:10.1093/jeb/voae025