Nevin Manimala

PLoS One. 2023 Aug 25;18(8):e0290260. doi: 10.1371/journal.pone.0290260. eCollection 2023.

ABSTRACT

BACKGROUND: Since the enforcement of the Movement Control Order (MCO) to contain the spread of COVID -19 infection in Malaysia, most clinic appointments have been rescheduled and procedures and surgeries postponed to a later date. Clinic appointments including intravitreal endothelial growth factor (anti-VEGF) treatment for patients with diabetic macular edema (DME) were also no exception to the postponement. This measure takes a psychological toll on patients because of the overwhelming concern for their eye condition. This study was conducted to assess the psychological status of DME patients with delayed anti-VEGF treatment during the pandemic.

METHODS: A cross-sectional study was conducted from September 2020 to March 2021 in Ophthalmology Clinic Hospital Canselor Tuanku Muhriz Universiti Kebangsaan Malaysia (HCTM UKM). Subjects diagnosed with center-involved DME aged between 20 to 80 years who experienced delayed anti-VEGF injection were recruited. Level of depression, anxiety and stress were assessed using DASS-21 questionnaire. Statistical analysis using non-parametric tests were performed to determine the relationship between the DASS-21 score and duration of last injection, in those whose vision was affected by delayed injection and the relationship to the impact of COVID-19 pandemic. Statistical significance was denoted as p < 0.05.

RESULTS: A total of 86 respondents with median age of 69 years old participated in this study. Most respondents were Malays (n = 47,54.7%) males (n = 51, 59.3%), had education up to secondary level (n = 37, 43%), unemployed (n = 78, 90.7%), married (n = 72, 83.7%) and living with their family (n = 82, 95.3%). The number of intravitreal injections received was at least three times among the respondents (n = 81, 94.2%). More than half of the respondents (n = 46, 53.5%) had been postponed for more than 12 weeks and felt that their vision was affected after delayed intravitreal injection (n = 47, 54.7%). Most of the subjects did not experience depression, anxiety, or stress. However, there was a significant level of stress scores among those with delayed injection of 9 to 12 weeks (p = 0.004), and significant anxiety (p = 0.029) and stress (p = 0.014) scores found in subjects with vision affected due to delayed treatment.

CONCLUSION: The level of anxiety and stress can be significant in DME patients who experienced delay in intravitreal anti-VEGF treatment. Assessment of psychosocial impacts is important to identify early mental health issues potentially leading to the onset of psychiatry illness, thus early intervention is indispensable.

PMID:37624864 | DOI:10.1371/journal.pone.0290260

PLoS One. 2023 Aug 25;18(8):e0290744. doi: 10.1371/journal.pone.0290744. eCollection 2023.

ABSTRACT

AIM: To compare cyclic fatigue resistance and bending for three different nickel-titanium (NiTi) rotary files.

MATERIALS AND METHODS: A sample of 90 NiTi instruments size (25.06) was divided into three groups with 30 files in each: Race Evo files (FKG Dentaire, Switzerland); Tia Tornado Blue files (TiaDent Inc., Texas- USA); One Curve files (Micro-Mega, France). Then each group was subdivided into two groups with 15 files in each; a bending test was performed for one group, and a dynamic cyclic fatigue test at body temperature was performed for the other group. Files fractured by cyclic fatigue were randomly picked from all tested groups for Scanning Electron Microscopy (SEM) (Jeol, Tokyo, Japan). In addition, the test included measuring the broken part of the files tested using (Electronic Micrometre Calliper with LCD Screen, Inch and Millimetre Conversion, Adoric- Taiwan). Data were statistically analyzed using a one-way ANOVA with Tukey-HSD post hoc test.

RESULTS: It was found that maximum load [gf] was less (meaning more flexible) in the group of Tia Tornado Blue with a statistically significant difference in comparison with Race Evo and One Curve. The number of cycles to fracture (NCF) in the Race Evo group was significantly higher than the groups of One Curve and Tia Tornado Blue.

CONCLUSIONS: Within the limitation of the study, it could be concluded that Race Evo files were more resistant to cyclic fatigue fracture and Tia Tornado Blue files were more flexible compared to the other tested files.

PMID:37624849 | DOI:10.1371/journal.pone.0290744

PLoS One. 2023 Aug 25;18(8):e0289838. doi: 10.1371/journal.pone.0289838. eCollection 2023.

ABSTRACT

INTRODUCTION: The prevalence of Diabetic Kidney Disease (DKD) secondary to Type 2 Diabetes Mellitus (T2DM) is rising worldwide. However, real-world data linking glomerular function and albuminuria to the degree of multi-morbidity is lacking. We thus utilised the Discover dataset, to determine this association.

METHOD: Patients with T2DM diagnosed prior to 1st January 2015 with no available biochemical evidence of CKD were included. Patients subsequently diagnosed and coded for CKD3a in 2015, were grouped by the degree of albuminuria. Baseline and 5-year co-morbidity was determined, as were prescribing practices with regards to prognostically beneficial medication.

RESULTS: We identified 56,261 patients with T2DM, of which 1082 had CKD stage 3a diagnosed in 2015 (224-CKD3aA1,154-CKD3aA2,93-CKD3aA1; 611 patients with CKD3a but no uACR available in 2015 were excluded from follow up). No statistically significant difference was observed in the degree of co-morbidities at baseline. A significant difference in the degree of hypertension, retinopathy, ischaemic heart disease and vascular disease from baseline compared to study end point was observed for all 3 study groups. Comparing co-morbidities developed at study end point, highlighted a statistical difference between CKD3aA1 Vs CKD3aA3 for retinopathy alone and for hypertension and heart failure between CKD3aA2 Vs CKD3aA3. 40.8% of patients with CKD3aA2 or A3 were prescribed Renin Angiotensin Aldosterone inhibitors (RAASi) therapy between June-December 2021. Survival analysis showed 15% of patients with CKD3aA3 developed CKD stage 5 within 5 years of diagnosis.

DISCUSSION: CKD3a secondary to DKD is associated with significant multimorbidity at baseline and 5 years post diagnosis, with CKD3aA3 most strongly associated with CKD progression to CKD 5, heart failure, hypertension and retinopathy compared to CKD3aA1 or CKD3aA2 at 5 years post diagnosis. The lack of uACR testing upon diagnosis and poor prescribing of RAASi, in those with CKD3aA2/A3, raises significant cause for concern.

CONCLUSION: DKD is associated with significant multimorbidity. Significant work is needed to be done to ensure patients undergo testing for uACR, to allow for future risk stratification and ability to be started on prognostically beneficial medication.

PMID:37624842 | DOI:10.1371/journal.pone.0289838

PLoS Comput Biol. 2023 Aug 25;19(8):e1011316. doi: 10.1371/journal.pcbi.1011316. Online ahead of print.

ABSTRACT

The ability to acquire abstract knowledge is a hallmark of human intelligence and is believed by many to be one of the core differences between humans and neural network models. Agents can be endowed with an inductive bias towards abstraction through meta-learning, where they are trained on a distribution of tasks that share some abstract structure that can be learned and applied. However, because neural networks are hard to interpret, it can be difficult to tell whether agents have learned the underlying abstraction, or alternatively statistical patterns that are characteristic of that abstraction. In this work, we compare the performance of humans and agents in a meta-reinforcement learning paradigm in which tasks are generated from abstract rules. We define a novel methodology for building “task metamers” that closely match the statistics of the abstract tasks but use a different underlying generative process, and evaluate performance on both abstract and metamer tasks. We find that humans perform better at abstract tasks than metamer tasks whereas common neural network architectures typically perform worse on the abstract tasks than the matched metamers. This work provides a foundation for characterizing differences between humans and machine learning that can be used in future work towards developing machines with more human-like behavior.

PMID:37624841 | DOI:10.1371/journal.pcbi.1011316

J Med Internet Res. 2023 Aug 25;25:e47284. doi: 10.2196/47284.

ABSTRACT

BACKGROUND: Chronic pain conditions involve numerous physical and psychological challenges, and while psychosocial self-management interventions can be of benefit for people living with chronic pain, such in-person treatment is not always accessible. Digital self-management approaches could improve this disparity, potentially bolstering outreach and providing easy, relatively low-cost access to pain self-management interventions.

OBJECTIVE: This randomized controlled trial aimed to evaluate the short-term efficacy of EPIO (ie, inspired by the Greek goddess for the soothing of pain, Epione), a digital self-management intervention, for people living with chronic pain.

METHODS: Patients (N=266) were randomly assigned to either the EPIO intervention (n=132) or a care-as-usual control group (n=134). Outcome measures included pain interference (Brief Pain Inventory; primary outcome measure), anxiety and depression (Hospital Anxiety and Depression Scale), self-regulatory fatigue (Self-Regulatory Fatigue 18 scale), health-related quality of life (SF-36 Short Form Health Survey), pain catastrophizing (Pain Catastrophizing Scale), and pain acceptance (Chronic Pain Acceptance Questionnaire). Linear regression models used change scores as the dependent variables.

RESULTS: The participants were primarily female (210/259, 81.1%), with a median age of 49 (range 22-78) years and a variety of pain conditions. Analyses (n=229) after 3 months revealed no statistically significant changes for the primary outcome of pain interference (P=.84), but significant reductions in the secondary outcomes of depression (mean difference -0.90; P=.03) and self-regulatory fatigue (mean difference -2.76; P=.008) in favor of the intervention group. No other statistically significant changes were observed at 3 months (all P>.05). Participants described EPIO as useful (ie, totally agree or agree; 95/109, 87.2%) and easy to use (101/109, 92.7%), with easily understandable exercises (106/109, 97.2%).

CONCLUSIONS: Evidence-informed, user-centered digital pain self-management interventions such as EPIO may have the potential to effectively support self-management and improve psychological functioning in the form of reduced symptoms of depression and improved capacity to regulate thoughts, feelings, and behavior for people living with chronic pain.

TRIAL REGISTRATION: ClinicalTrials.gov NCT03705104; https://clinicaltrials.gov/ct2/show/NCT03705104.

PMID:37624622 | DOI:10.2196/47284

Transl Vis Sci Technol. 2023 Aug 1;12(8):21. doi: 10.1167/tvst.12.8.21.

ABSTRACT

PURPOSE: To investigate and compare novel volumetric microperimetry (MP)-derived metrics in intermediate age-related macular degeneration (iAMD), as current MP metrics show high variability and low sensitivity.

METHODS: This is a cross-sectional analysis of microperimetry baseline data from the multicenter, prospective PINNACLE study (ClinicalTrials.gov NCT04269304). The Visual Field Modeling and Analysis (VFMA) software and an open-source implementation (OSI) were applied to calculate MP-derived hill-of-vison (HOV) surface plots and the total volume (VTOT) beneath the plots. Bland-Altman plots were used for methodologic comparison, and the association of retinal sensitivity metrics with explanatory variables was tested with mixed-effects models.

RESULTS: In total, 247 eyes of 189 participants (75 ± 7.3 years) were included in the analysis. The VTOT output of VFMA and OSI exhibited a significant difference (P < 0.0001). VFMA yielded slightly higher coefficients of determination than OSI and mean sensitivity (MS) in univariable and multivariable modeling, for example, in association with low-luminance visual acuity (LLVA) (marginal R2/conditional R2: VFMA 0.171/0.771, OSI 0.162/0.765, MS 0.133/0.755). In the multivariable analysis, LLVA was the only demonstrable predictor of VFMA VTOT (t-value, P-value: -7.5, <0.001) and MS (-6.5, <0.001).

CONCLUSIONS: The HOV-derived metric of VTOT exhibits favorable characteristics compared to MS in evaluating retinal sensitivity. The output of VFMA and OSI is not exactly interchangeable in this cross-sectional analysis. Longitudinal analysis is necessary to assess their performance in ability-to-detect change.

TRANSLATIONAL RELEVANCE: This study explores new volumetric MP endpoints for future application in therapeutic trials in iAMD and reports specific characteristics of the available HOV software applications.

PMID:37624605 | DOI:10.1167/tvst.12.8.21

JAMA Netw Open. 2023 Aug 1;6(8):e2330885. doi: 10.1001/jamanetworkopen.2023.30885.

ABSTRACT

IMPORTANCE: Recurrent flares are the hallmark of clinical manifestation of gout. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been associated with a lower risk of incident gout; however, their association with recurrent flares is unknown.

OBJECTIVE: To examine the association of SGLT2i vs active comparators (ie, glucagonlike peptide-1 receptor agonists [GLP-1 RA] or dipeptidyl peptidase-4 inhibitors [DPP-4i]) with the risk of recurrent gout flares and all-cause mortality among patients with gout and type 2 diabetes.

DESIGN, SETTING, AND PARTICIPANTS: This population-based retrospective cohort study was performed from January 1, 2013, to March 31, 2022, using a UK primary care database. Participants included patients with gout and type 2 diabetes with visits to their general practitioners.

EXPOSURES: Initiation of treatment with SGLT2i or active comparators.

MAIN OUTCOMES AND MEASURES: The primary outcome was the number of recurrent gout flares ascertained using recorded codes and prescription records. Secondary outcomes were the first recurrent gout flare and all-cause mortality. The association of SGLT2i compared with active comparators for the risk of recurrent flares, the first recurrent flare, and all-cause mortality was assessed using Poisson regression or the Cox proportional hazards model with propensity score overlap weighting.

RESULTS: Of a total of 5931 patients included in the analysis (mean [SD] age, 66.0 [11.6] years; 4604 [77.6%] men), 1548 initiated SGLT2i treatment and 4383 initiated treatment with active comparators during the study period. The relative rate of the recurrent flares with SGLT2i vs active comparators was 0.79 (95% CI, 0.65-0.97). Similar results were observed in the association of SGLT2i with the rate of recurrent flares when compared with DPP-4i or GLP-1 RA. For the first recurrent flare for SGLT2i vs active comparators, rate difference was -8.8 (95% CI, -17.2 to -0.4) per 1000 person-years and the hazard ratio was 0.81 (95% CI, 0.65-0.98). All-cause mortality per 1000 person-years was 18.8 for SGLT2i and 24.9 for active comparators, with rate difference of -6.1 (95% CI, -10.6 to -1.6) per 1000 person-years and hazard ratio of 0.71 (95% CI, 0.52-0.97).

CONCLUSIONS AND RELEVANCE: The findings of this cohort study suggest that SGLT2i were associated with a lower risk of recurrent gout flares and mortality than their active comparators in patients with gout and type 2 diabetes. These findings further suggest that SGLT2i could help reduce the burden of recurrent gout flares and could also narrow the mortality gap between patients with gout and the general population.

PMID:37624597 | DOI:10.1001/jamanetworkopen.2023.30885

Discov Oncol. 2023 Aug 25;14(1):155. doi: 10.1007/s12672-023-00777-1.

ABSTRACT

BACKGROUND: Cellular senescence is growing in popularity in cancer. A dual function is played by the senescence-associated secretory phenotype (SASP) that senescent cells produce in the development of pro-inflammatory niches, tissue regeneration or destruction, senescence propagation, and malignant transformation. In this study, we conducted thorough bioinformatic analysis and meta-analysis to discover detrimental and beneficial subtypes and prognostic index for prostate cancer (PCa) patients using the experimentally confirmed SASP genes.

METHODS: We identified differentially expressed and prognosis-related SASP genes and used them to construct two molecular subtypes and risk score. Another two external cohorts were used to confirm the prognostic effect of the above subtypes and risk score and meta-analysis was further conducted. Additionally, functional analysis, tumor stemness and heterogeneity and tumor microenvironment were also evaluated. We completed analyses using software R 3.6.3 and its suitable packages. Meta-analysis was performed by software Stata 14.0.

RESULTS: Through multivariate Cox regression analysis and consensus clustering analysis, we used VGF, IGFBP3 and ANG to establish detrimental and beneficial subtypes in the TCGA cohort, which was validated through other two independent cohorts. Meta-analysis showed that detrimental SASP group had significantly higher risk of biochemical recurrence (BCR) than beneficial SASP group (HR: 2.48). Moreover, we also constructed and validated risk score based on these genes to better guide clinical practice. DNA repair, MYC target, oxidative phosphorylation, proteasome and ribosome were highly enriched in detrimental SASP group. Detrimental SASP group had significantly higher levels of B cells, CD8+ T cells, homologous recombination deficiency, loss of heterozygosity, microsatellite instability, purity, tumor mutation burden, mRNAsi, differentially methylated probes and epigenetically regulated RNA expression than beneficial SASP group. The top mutation genes between detrimental and beneficial SASP groups were SPOP, FOXA1, KMT2C, APC, BSN, DNAH17, MYH6, EPPK1, ZNF536 and ZC3H13 with statistical significance.

CONCLUSIONS: From perspective of SASP, we found detrimental and beneficial tumor subtypes which were closely associated with BCR-free survival for PCa patients, which might be important for the furture research in the field of PCa.

PMID:37624511 | DOI:10.1007/s12672-023-00777-1

Environ Sci Pollut Res Int. 2023 Aug 25. doi: 10.1007/s11356-023-29419-3. Online ahead of print.

ABSTRACT

In recent years, attention has been focused on the benefit of greenspace on mental health, and it is suggested this link may vary with the type of greenspace. More and more studies have emphasized the influence of the gut microbiome on schizophrenia (SCZ). However, the effects of greenspaces on the gut microbiota in SCZ and the effect of different types of greenspaces on the gut microbiota remain unclear. We aim to examine if there were variations in the effects of various greenspace types on the gut microbiome in SCZ. Besides, we sink to explore important taxonomic compositions associated with different greenspace types. We recruited 243 objects with schizophrenia from Anhui Mental Health Center and collected fecal samples for 16Sr RNA gene sequencing. Three types of greenery coverage were calculated with different circular buffers (800, 1500, and 3000 m) corresponding to individual addresses. The association between greenspace and microbiome composition was analyzed with permutational analysis of variance (PERMANOVA). We conducted the linear regression to capture specific gut microbiome taxa associated with greenery coverage. Tree coverage was consistently associated with microbial composition in both 1500 m (R² = 0.007, P = 0.030) and 3000 m (R² = 0.007, P = 0.039). In contrast, there was no association with grass cover in any of the buffer zones. In the regression analysis, higher tree coverage was significantly correlated with the relative abundance of several taxa. Among them, tree coverage was positively associated with increased Bifidobacterium longum (β = 1.069, P = 0.004), which was the dominant composition in the gut microbiota. The relationship between greenspace and gut microbiome in SCZ differed by the type of greenspace. Besides, “tree coverage” may present a dominant effect on the important taxonomic composition. Our findings might provide instructive evidence for the design of urban greenspace to optimize health and well-being in SCZ as well as the whole people.

PMID:37624502 | DOI:10.1007/s11356-023-29419-3

J Robot Surg. 2023 Aug 25. doi: 10.1007/s11701-023-01698-5. Online ahead of print.

ABSTRACT

Robotic-assisted breast surgery (RABS) is controversial. We systematically reviewed the evidence about RABS, comparing it to open conventional breast surgery (CBS). Following prospective registration (osf.io/97ewt), a search was performed in January 2023, without time or language restrictions, through bibliographic databases (PubMed, Web of Science, EMBASE, Scopus, Trip database and CDSR) and grey literature. Quality was assessed in duplicate using Qualsyst criteria (score range 0.0-1.0); reviewer agreement was 98%. The 16 selected studies (total patients: 334,804) had overall high quality (mean score 0.82; range 0.68-0.91). Nine of 16 (56.3%) were cohort studies, 2/16 (12.5%) RCTs, and 5/16 (31.3%) case-control studies. Taking p < 0.05 as the significance threshold, RABS versus CBS was better in aesthetic results and patient satisfaction (10/11 studies; 90%), was surgically costly (4/4 studies; 100%), time-consuming (9/13 studies; 69%), and less painful in the first 6-24 h (2/2 studies; 100%) and without statistically significant differences in complication rates (10/12 studies; 83%) or short-term oncological outcomes (10/10 studies; 100%). Surgical time could be dramatically reduced by training surgical teams, reaching no significant differences between approaches (p = 0.120). RABS was shown to be feasible and safe. The advantages of RABS and long-term outcomes need further research.

PMID:37624486 | DOI:10.1007/s11701-023-01698-5