Category: Nevin Manimala

Sci Signal. 2023 Jan 17;16(768):eabh1083. doi: 10.1126/scisignal.abh1083. Epub 2023 Jan 17.

ABSTRACT

Inflammasomes are intracellular protein complexes that promote an inflammatory host defense in response to pathogens and damaged or neoplastic tissues and are implicated in inflammatory disorders and therapeutic-induced toxicity. We investigated the mechanisms of activation for inflammasomes nucleated by NOD-like receptor (NLR) protiens. A screen of a small-molecule library revealed that several tyrosine kinase inhibitors (TKIs)-including those that are clinically approved (such as imatinib and crizotinib) or are in clinical trials (such as masitinib)-activated the NLRP3 inflammasome. Furthermore, imatinib and masitinib caused lysosomal swelling and damage independently of their kinase target, leading to cathepsin-mediated destabilization of myeloid cell membranes and, ultimately, cell lysis that was accompanied by potassium (K⁺) efflux, which activated NLRP3. This effect was specific to primary myeloid cells (such as peripheral blood mononuclear cells and mouse bone marrow-derived dendritic cells) and did not occur in other primary cell types or various cell lines. TKI-induced lytic cell death and NLRP3 activation, but not lysosomal damage, were prevented by stabilizing cell membranes. Our findings reveal a potential immunological off-target of some TKIs that may contribute to their clinical efficacy or to their adverse effects.

PMID:36649377 | DOI:10.1126/scisignal.abh1083

PLoS One. 2023 Jan 17;18(1):e0278670. doi: 10.1371/journal.pone.0278670. eCollection 2023.

ABSTRACT

BACKGROUND: The mother-to-child transmission of HIV-1 (MTCT) remains on the major route of HIV-transmission among pediatric populations in Africa. Though a prevention of MTCT (PMTCT) high-priority country, data on the MTCT burdens in Cameroon remains fragmented.

OBJECTIVE: We sought to assess the pooled MTCT rate, its risk-factors, and to characterize viral reservoirs of infected-children in Cameroon.

METHODS: All relevant observational cohort and cross-sectional studies conducted in Cameroon were searched from PubMed, African Journals Online, Google scholar, ScienceDirect and academic medical education databases. Heterogeneity and publication bias were respectively assessed by the I2 statistic and the Egger/funnel plot test. Meta-analysis was performed using the random effects model. MTCT rate >5% was considered as “high”. This review was registered in the Prospero database, CRD42021224497.

RESULTS: We included a total of 29 studies and analyzed 46 684 children born from HIV-positive mothers. The overall rate of MTCT was 7.00% (95% CI = 6.07-8.51). According to regions, the highest burden was in Adamaoua-region (17.51% [95% CI:14.21-21.07]) with only one study found. PMTCT option-B+ resulted in about 25% reduction of MTCT (8.97% [95% CI: 8.71-9.24] without option-B+ versus 2.88% [95% CI: 5.03-9.34] with option-B+). Regarding risk-factors, MTCT was significantly associated with the absence of PMTCT-interventions both in children (OR:5.40 [95% CI: 2.58-11.27]) and mothers (OR: 3.59 [95% CI: 2.15-5.99]). Regarding viral reservoirs, a pro-viral DNA mean of 3.34±1.05 log10/mL was observed among 5/57 children and archived HIV drug resistance mutations were identified in pro-viral DNA marker among 21/79 infected-children.

CONCLUSION: In spite of the dropdown in MTCT following option-B+ implementation, MTCT remains high in Cameroon, with substantial disparities across regions. Thus, in this era of option-B+, achieving MTCT elimination requires interventions in northern-Cameroon. The variation in pro-viral load in infected-children underlines the relevance of characterizing viral reservoirs for possible infection control in tropical settings.

PMID:36649370 | DOI:10.1371/journal.pone.0278670

PLoS One. 2023 Jan 17;18(1):e0278665. doi: 10.1371/journal.pone.0278665. eCollection 2023.

ABSTRACT

Our knowledge about the underlying pathomechanisms of craniocervical junction abnormalities (CCJA) in dogs mostly derives from measurements based on tomographic imaging. These images are static and the positioning of the dogs’ head does not reflect the physiological in vivo position of the craniocervical junction (CCJ). Aberrant motion patterns and ranges of motion (ROM) in sound individuals of CCJA predisposed breeds may be a pathogenetic trigger. To further extend our limited knowledge of physiological motion of the CCJ, this prospective, comparative study investigates the in vivo motion patterns and ROM of the CCJ in walk and trot in sound Cavalier King Charles Spaniels and Chihuahuas. The Labrador retriever is used as a reference breed without predisposition for CCJA. This is the first detailed description of CCJ movement of trotting dogs. Biplanar fluoroscopy images, recorded in walking and trotting dogs, were matched to a virtual reconstruction of the skull and cranial cervical spine utilising Scientific Rotoscoping. Kinematic data reveal the same motion patterns among all breeds and gaits with individual temporal and spatial differences in each dog. A stride cycle-dependent lateral rotation of the cranial cervical spine and axial rotation of the atlantoaxial joint in trot in dogs is described for the first time. The ROM of the atlantoaxial and atlantooccipital joints in walk and trot were not statistically significantly greater in the CCJA-predisposed breeds CKCS and Chihuahua. ROM values of all translational and rotational degrees of freedom were larger in walk than trot, although this is only statistically significant for the atlantoaxial joint. Until proven otherwise, a more species-specific than breed-specific general motion pattern of the CCJ in walking and trotting, clinically sound dogs must be assumed. Species-specific anatomic properties of the CCJ seem to supersede breed-specific anatomical differences in clinically sound dogs.

PMID:36649366 | DOI:10.1371/journal.pone.0278665

PLoS One. 2023 Jan 17;18(1):e0277085. doi: 10.1371/journal.pone.0277085. eCollection 2023.

ABSTRACT

The prediction of energy consumption is of great significance to the stability of the regional energy supply. In previous research on energy consumption forecasting, researchers have constantly proposed improved neural network prediction models or improved machine learning models to predict time series data. Combining the well-performing machine learning model and neural network model in energy consumption prediction, we propose a hybrid model architecture of GRU-MMattention-LightGBM with feature selection based on Prophet decomposition. During the prediction process, first, the prophet features are extracted from the original time series. We select the best LightGBM model in the training set and save the best parameters. Then, the Prophet feature is input to GRU-MMattention for training. Finally, MLP is used to learn the final prediction weight between LightGBM and GRU-MMattention. After the prediction weights are learned, the final prediction result is determined. The innovation of this paper lies in that we propose a structure to learn the internal correlation between features based on Prophet feature extraction combined with the gating and attention mechanism. The structure also has the characteristics of a strong anti-noise ability of the LightGBM method, which can reduce the impact of the energy consumption mutation point on the overall prediction effect of the model. In addition, we propose a simple method to select the hyperparameters of the time window length using ACF and PACF diagrams. The MAPE of the GRU-MMattention-LightGBM model is 1.69%, and the relative error is 8.66% less than that of the GRU structure and 2.02% less than that of the LightGBM prediction. Compared with a single method, the prediction accuracy and stability of this hybrid architecture are significantly improved.

PMID:36649365 | DOI:10.1371/journal.pone.0277085

PLoS Med. 2023 Jan 17;20(1):e1004166. doi: 10.1371/journal.pmed.1004166. Online ahead of print.

ABSTRACT

BACKGROUND: Globally, access to life-saving vaccines has improved considerably in the past 5 decades. However, progress has started to slow down and even reverse in recent years. Understanding subnational heterogeneities in essential child immunization will be critical for closing the global vaccination gap.

METHODS AND FINDINGS: We use vaccination information for over 220,000 children across 1,366 administrative regions in 43 low- and middle-income countries (LMICs) from the most recent Demographic and Health Surveys. We estimate essential immunization coverage at the national and subnational levels and quantify socioeconomic inequalities in such coverage using adjusted concentration indices. Within- and between-country variations are summarized via the Theil index. We use local indicator of spatial association (LISA) statistics to identify clusters of administrative regions with high or low values. Finally, we estimate the number of missed vaccinations among children aged 15 to 35 months across all 43 countries and the types of vaccines most often missed. We show that national-level vaccination rates can conceal wide subnational heterogeneities. Large gaps in child immunization are found across West and Central Africa and in South Asia, particularly in regions of Angola, Chad, Nigeria, Guinea, and Afghanistan, where less than 10% of children are fully immunized. Furthermore, children living in these countries consistently lack all 4 basic vaccines included in the WHO’s recommended schedule for young children. Across most countries, children from poorer households are less likely to be fully immunized. The main limitations include subnational estimates based on large administrative divisions for some countries and different periods of survey data collection.

CONCLUSIONS: The identified heterogeneities in essential childhood immunization, especially given that some regions consistently are underserved for all basic vaccines, can be used to inform the design and implementation of localized intervention programs aimed at eliminating child suffering and deaths from existing and novel vaccine-preventable diseases.

PMID:36649359 | DOI:10.1371/journal.pmed.1004166

J Med Internet Res. 2023 Jan 17;25:e43532. doi: 10.2196/43532.

ABSTRACT

BACKGROUND: The minority stress model postulates that men who have sex with men (MSM) often encounter multiple stressors because of their sexual minority status, which may lead to psychological problems and maladaptive coping such as addictive behaviors (eg, internet gaming disorder [IGD]). It was hypothesized that hopelessness and loneliness would be associated with IGD via self-control among MSM.

OBJECTIVE: This study investigated the prevalence of IGD and its associations with variables related to minority stress (loneliness and hopelessness) among MSM who were university students. Mediation involving such associations via self-control was also explored.

METHODS: With informed consent, 305 MSM attending universities in Sichuan, China participated in the study. The validated Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) checklist was used to assess IGD. Multivariable logistic regression adjusted for background factors and structural equation modeling were conducted.

RESULTS: The prevalence of IGD was 12.8% (n=39). Logistic regression found that IGD was positively associated with hopelessness and loneliness, and negatively associated with self-control. The structural equation modeling identified three significant paths between hopelessness/loneliness and IGD: (1) hopelessness → lower self-control → higher IGD (full mediation), (2) loneliness → lower self-control → higher IGD (partial mediation: effect size of 28%), and (3) a direct effect from loneliness to IGD.

CONCLUSIONS: IGD was prevalent among young MSM and warrants interventions that may try to reduce the level of psychosocial problems such as loneliness and hopelessness and improve self-control. According to the socioecological model, the promotion of social acceptance and reduction in stigma toward MSM are important in reducing loneliness and hopefulness among MSM. Self-control links up the relationships between psychosocial problems and IGD and should be given special attention. Longitudinal studies are warranted to confirm the findings and test new mediations between loneliness/hopelessness and MSM with IGD.

PMID:36649059 | DOI:10.2196/43532

JMIR Form Res. 2023 Jan 17;7:e38112. doi: 10.2196/38112.

ABSTRACT

BACKGROUND: Individuals with later bedtimes have an increased risk of difficulties with mood and substances. To investigate the causes and consequences of late bedtimes and other sleep patterns, researchers are exploring social media as a data source. Pioneering studies inferred sleep patterns directly from social media data. While innovative, these efforts are variously unscalable, context dependent, confined to specific sleep parameters, or rest on untested assumptions, and none of the reviewed studies apply to the popular Reddit platform or release software to the research community.

OBJECTIVE: This study builds on this prior work. We estimate the bedtimes of Reddit users from the times tamps of their posts, test inference validity against survey data, and release our model as an R package (The R Foundation).

METHODS: We included 159 sufficiently active Reddit users with known time zones and known, nonanomalous bedtimes, together with the time stamps of their 2.1 million posts. The model’s form was chosen by visualizing the aggregate distribution of the timing of users’ posts relative to their reported bedtimes. The chosen model represents a user’s frequency of Reddit posting by time of day, with a flat portion before bedtime and a quadratic depletion that begins near the user’s bedtime, with parameters fitted to the data. This model estimates the bedtimes of individual Reddit users from the time stamps of their posts. Model performance is assessed through k-fold cross-validation. We then apply the model to estimate the bedtimes of 51,372 sufficiently active, nonbot Reddit users with known time zones from the time stamps of their 140 million posts.

RESULTS: The Pearson correlation between expected and observed Reddit posting frequencies in our model was 0.997 on aggregate data. On average, posting starts declining 45 minutes before bedtime, reaches a nadir 4.75 hours after bedtime that is 87% lower than the daytime rate, and returns to baseline 10.25 hours after bedtime. The Pearson correlation between inferred and reported bedtimes for individual users was 0.61 (P<.001). In 90 of 159 cases (56.6%), our estimate was within 1 hour of the reported bedtime; 128 cases (80.5%) were within 2 hours. There was equivalent accuracy in hold-out sets versus training sets of k-fold cross-validation, arguing against overfitting. The model was more accurate than a random forest approach.

CONCLUSIONS: We uncovered a simple, reproducible relationship between Reddit users’ reported bedtimes and the time of day when high daytime posting rates transition to low nighttime posting rates. We captured this relationship in a model that estimates users’ bedtimes from the time stamps of their posts. Limitations include applicability only to users who post frequently, the requirement for time zone data, and limits on generalizability. Nonetheless, it is a step forward for inferring the sleep parameters of social media users passively at scale. Our model and precomputed estimated bedtimes of 50,000 Reddit users are freely available.

PMID:36649054 | DOI:10.2196/38112

Vision (Basel). 2022 Dec 28;7(1):3. doi: 10.3390/vision7010003.

ABSTRACT

Most people are good at estimating summary statistics for different features of groups of objects. For instance, people can selectively attend to different features of a group of lines and report ensemble properties such as the mean length or mean orientation and there are reliable individual differences in such ensemble judgment abilities. Our recent study found decisive evidence in support of a correlation between the errors on mean length and mean orientation judgments (r = 0.62). The present study investigates one possible mechanism for this correlation. The ability to allocate spatial attention to single items varies across individuals, and in the recent study, this variability could have contributed to both judgments because the location of lines was unpredictable. Here, we replicate this prior work with arrays of lines with fully predictable spatial locations, to lower the contribution of the ability to distribute attention effectively over all items in a display. We observed a strong positive correlation between errors on the length and orientation averaging tasks (r = 0.65). This provides evidence against individual differences in spatial attention as a common mechanism supporting mean length and orientation judgments. The present result aligns with the growing evidence for at least one ensemble-specific ability that applies across different kinds of features and stimuli.

PMID:36649050 | DOI:10.3390/vision7010003

Med Sci (Basel). 2022 Dec 20;11(1):1. doi: 10.3390/medsci11010001.

ABSTRACT

The purpose of this study was to determine the effect of sublethal concentrations of nitrofurantoin, ciprofloxacin, and trimethoprim on biofilm formation in 57 uropathogenic Escherichia coli strains (UPEC). The minimum inhibitory concentration of nitrofurantoin, ciprofloxacin, and trimethoprim was determined and the biofilm formation for each isolate with and without sub-lethal concentrations of each antibiotic was then quantified. The statistical significance of changes in biofilm formation was ascertained by way of a Dunnett’s test. A total of 22.8% of strains were induced to form stronger biofilms by nitrofurantoin, 12% by ciprofloxacin, and 19% by trimethoprim; conversely 36.8% of strains had inhibited biofilm formation with nitrofurantoin, 52.6% with ciprofloxacin, and 38.5% with trimethoprim. A key finding was that even in cases where the isolate was resistant to an antibiotic as defined by EUCAST, many were induced to form a stronger biofilm when grown with sub-MIC concentrations of antibiotics, especially trimethoprim, where six of the 22 trimethoprim resistant strains were induced to form stronger biofilms. These findings suggest that the use of empirical treatment with trimethoprim without first establishing susceptibility may in fact potentiate infection in cases where a patient who is suffering from a urinary tract infection (UTI) caused by trimethoprim resistant UPEC is administered trimethoprim. This emphasizes the need for laboratory-guided treatment of UTI.

PMID:36649038 | DOI:10.3390/medsci11010001

Pharmacy (Basel). 2022 Dec 21;11(1):1. doi: 10.3390/pharmacy11010001.

ABSTRACT

The COVID-19 pandemic required pharmacists in a provincial Home Dialysis Clinic to adapt from in-person to telephone-based medication reviews. Studies have shown that in-person pharmacist interventions in patients with chronic kidney disease (CKD) lead to a reduction of drug therapy problems (DTPs), however, it’s unknown if telephone interventions provide similar outcomes. The purpose of this study was to evaluate whether differences in quality of care exist between in-person vs. telephone medication reviews in home dialysis patients and to evaluate patient satisfaction with telephone medication reviews. Data from the two most recent in-person medication reviews was compared with the two most recent telephone medication reviews for each patient (n = 46). There were no statistically significant differences in DTPs identified between in-person and telephone medication reviews (p = 0.431). Physician acceptance of pharmacist recommendations was higher for in-person medication reviews (p = 0.009). Patients were satisfied with the care they received with pharmacist-led telephone medication reviews, however, 29% (n = 7) would prefer an in-person medication review once per year with telephone medication reviews the rest of the time. Overall, patients were satisfied with the care they received from telephone medication reviews.

PMID:36649011 | DOI:10.3390/pharmacy11010001