Tag: nevin manimala

J Chem Inf Model. 2022 Nov 18. doi: 10.1021/acs.jcim.2c01115. Online ahead of print.

ABSTRACT

The advances in ligand binding affinity prediction have been fostered by system generation tools and improved force fields (FFs). CHARMM-GUI Free Energy Calculator provides input and postprocessing scripts for AMBER-TI free energy calculations with various FFs. In this study, we used 12 different FF combinations (ff14SB and ff19SB for protein, GAFF2.2 and OpenFF for ligand, and TIP3P, TIP4PEW, and OPC for water) to calculate relative binding free energies (ΔΔG_bind) for 80 alchemical transformations (among the JACS benchmark set) with different numbers of λ windows (12 or 21) and simulation times (1, 5, or 10 ns). Our results show that 12 λ windows and 5 ns simulation time for each window are sufficient to obtain reliable ΔΔG_bind with 4 independent runs for the current benchmark set. While there is no statistically noticeable performance difference among 12 different FF combinations compared to the experimental values, a combination of ff14SB + GAFF2.2 + TIP3P FFs appears to be best with a mean unsigned error of 0.87 [0.69, 1.07] kcal/mol, a root-mean-square error of 1.22 [0.94, 1.50] kcal/mol, a Pearson’s correlation of 0.64 [0.52, 0.76], a Spearman’s correlation of 0.73 [0.58, 0.83], and a Kendell’s correlation of 0.54 [0.42, 0.64]. This large-scale ΔΔG_bind calculation study provides useful information about ΔΔG_bind prediction with different AMBER FF combinations and presents valuable suggestions for FF selection in AMBER-TI ΔΔG_bind calculations.

PMID:36399655 | DOI:10.1021/acs.jcim.2c01115

J Womens Health (Larchmt). 2022 Nov 18. doi: 10.1089/jwh.2022.0153. Online ahead of print.

ABSTRACT

Background: Osteoporosis is common among older adults. Women are more likely to have osteoporosis than men. The prevalence varies with race/ethnicity, with the highest prevalence observed among non-Hispanic, Asian women. Prior studies identified a negative association between smoking and bone mineral density (BMD). The association between smoking and osteoporosis has not been investigated according to race/ethnicity. Materials and Methods: We included 4,226 U.S. adults aged 50 years or older with complete information on smoking history, BMD, and other independent variables from the 2005-2010 National Health and Nutrition Examination Surveys. Design-based multinomial logistic regression was utilized to estimate prevalence odds ratios (POR) of osteoporosis (T-score ≤ -2.5) and of low bone density (T-score between -1.0 and -2.5) in relation to lifetime smoking pack-years, stratified by sex and race/ethnicity. Results: Participants were 61.5 (standard error 0.21) years old on average and 48% women (n = 2,027). Among women, a smoking history ≥30 pack-years was positively associated with osteoporosis (POR: 2.40; 95% confidence interval [CI]: 1.42-4.06). Similar POR were observed among non-Hispanic White, non-Hispanic Black, and Mexican American women. However, POR for ≥30 pack-years and low bone density were positive but not statistically significant. Among men, null associations of smoking history, osteoporosis, and low bone density were observed, except for a positive association of ≥30 pack-years and low bone density among non-Hispanic Black men. Conclusion: Osteoporosis was twice as prevalent among women who smoked ≥30 pack-years than among women who never smoked, regardless of race/ethnicity. Smoking history and osteoporosis were not associated among men.

PMID:36399604 | DOI:10.1089/jwh.2022.0153

Mol Pharm. 2022 Nov 18. doi: 10.1021/acs.molpharmaceut.2c00744. Online ahead of print.

ABSTRACT

Cowpea mosaic virus (CPMV) has been developed as a promising nanoplatform technology for cancer immunotherapy; when applied as in situ vaccine, CPMV exhibits potent, systemic, and durable efficacy. While CPMV is not infectious to mammals, it is infectious to legumes; therefore, agronomic safety needs to be addressed to broaden the translational application of CPMV. RNA-containing formulations are preferred over RNA-free virus-like particles because the RNA and protein, each, contribute to CPMV’s potent antitumor efficacy. We have previously optimized inactivation methods to develop CPMV that contains RNA but is not infectious to plants. We established that inactivated CPMV has reduced efficacy compared to untreated, native CPMV. However, a systematic comparison between native CPMV and different inactivated forms of CPMV was not done. Therefore, in this study, we directly compared the therapeutic efficacies and mechanisms of immune activation of CPMV, ultraviolet- (UV-), and formalin (Form)-inactivated CPMV to explain the differential efficacies. In a B16F10 melanoma mouse tumor model, Form-CPMV suppressed the tumor growth with prolonged survival (there were no statistical differences comparing CPMV and Form-CPMV). In comparison, UV-CPMV inhibited tumor growth significantly but not as well as Form-CPMV or CPMV. The reduced therapeutic efficacy of UV-CPMV is explained by the degree of cross-linking and aggregated state of the RNA, which renders it inaccessible for sensing by Toll-like receptor (TLR) 7/8 to activate immune responses. The mechanistic studies showed that the highly aggregated state of UV-CPMV inhibited TLR7 signaling more so than for the Form-CPMV formulation, reducing the secretion of interleukin-6 (IL-6) and interferon-α (IFN-α), cytokines associated with TLR7 signaling. These findings support the translational development of Form-CPMV as a noninfectious immunotherapeutic agent.

PMID:36399598 | DOI:10.1021/acs.molpharmaceut.2c00744

IEEE J Biomed Health Inform. 2022 Nov 18;PP. doi: 10.1109/JBHI.2022.3223181. Online ahead of print.

ABSTRACT

With the advancement in artificial intelligence (AI) based E-healthcare applications, the role of automated diagnosis of various diseases has increased at a rapid rate. However, most of the existing diagnosis models provide results in a binary fashion such as whether the patient is infected with a specific disease or not. But there are many cases where it is required to provide suitable explanatory information such as the patient being infected from a particular disease along with the infection rate. Therefore, in this paper, to provide explanatory information to the doctors and patients, an efficient deep ensemble medical image captioning network (DCNet) is proposed. DCNet ensembles three well-known pre-trained models such as VGG16, ResNet152V2, and DenseNet201. Ensembling of these models achieves better results by preventing an over-fitting problem. However, DCNet is sensitive to its control parameters. Thus, to tune the control parameters, an evolving DCNet (EDC-Net) was proposed. Evolution process is achieved using the self-adaptive parameter control-based differential evolution (SAPCDE). Experimental results show that EDC-Net can efficiently extract the potential features of biomedical images. Comparative analysis shows that on the Open-i dataset, EDC-Net outperforms the existing models in terms of BLUE-1, BLUE-2, BLUE-3, BLUE-4, and kappa statistics (KS) by 1.258%, 1.185%, 1.289%, 1.098%, and 1.548%, respectively.

PMID:36399583 | DOI:10.1109/JBHI.2022.3223181

J Comput Assist Tomogr. 2022 Nov-Dec 01;46(6):888-893. doi: 10.1097/RCT.0000000000001372. Epub 2022 Oct 19.

ABSTRACT

OBJECTIVE: This study investigated the use of routine contrast-enhanced chest computed tomography (CT) to diagnose unsuspected pulmonary embolism (PE).

METHODS: All adult routine contrast-enhanced chest CTs performed at Montefiore in 2018 were included. Pulmonary artery enhancement was measured by placing regions of interest in the pulmonary vasculature. Adequate enhancement was defined as 200 Hounsfield units (HU) or greater. Presence or absence of PE was noted. Descriptive statistics and logistic regression analysis were performed.

RESULTS: A total of 3164 CTs were evaluated (55.8% women; mean age, 63.2 years). Main pulmonary enhancement was highly correlated with peripheral enhancement. Of all cases, 28.7% (907 of 3164) reached the 200 HU threshold. Greater enhancement was associated with female sex, older age, outpatients, and contrast amount administered. Pulmonary embolism-positive cases comprised 1.8% (58 of 3164) of total cases. Furthermore, 39.7% (23 of 58) of PE-positive cases reached the 200 HU threshold.

CONCLUSIONS: Over one quarter of routine contrast-enhanced chest CT scans met the 200 HU threshold indicative of adequate pulmonary artery enhancement, including nearly half of the 2% of examinations positive for PE.

PMID:36399535 | DOI:10.1097/RCT.0000000000001372

Nucleic Acids Res. 2022 Nov 18:gkac1068. doi: 10.1093/nar/gkac1068. Online ahead of print.

ABSTRACT

Carbohydrate Active EnZymes (CAZymes) are significantly important for microbial communities to thrive in carbohydrate rich environments such as animal guts, agricultural soils, forest floors, and ocean sediments. Since 2017, microbiome sequencing and assembly have produced numerous metagenome assembled genomes (MAGs). We have updated our dbCAN-seq database (https://bcb.unl.edu/dbCAN_seq) to include the following new data and features: (i) ∼498 000 CAZymes and ∼169 000 CAZyme gene clusters (CGCs) from 9421 MAGs of four ecological (human gut, human oral, cow rumen, and marine) environments; (ii) Glycan substrates for 41 447 (24.54%) CGCs inferred by two novel approaches (dbCAN-PUL homology search and eCAMI subfamily majority voting) (the two approaches agreed on 4183 CGCs for substrate assignments); (iii) A redesigned CGC page to include the graphical display of CGC gene compositions, the alignment of query CGC and subject PUL (polysaccharide utilization loci) of dbCAN-PUL, and the eCAMI subfamily table to support the predicted substrates; (iv) A statistics page to organize all the data for easy CGC access according to substrates and taxonomic phyla; and (v) A batch download page. In summary, this updated dbCAN-seq database highlights glycan substrates predicted for CGCs from microbiomes. Future work will implement the substrate prediction function in our dbCAN2 web server.

PMID:36399503 | DOI:10.1093/nar/gkac1068

PLoS One. 2022 Nov 18;17(11):e0277917. doi: 10.1371/journal.pone.0277917. eCollection 2022.

ABSTRACT

After a major upper limb amputation, the use of myoelectric prosthesis as assistive devices is possible. However, these prostheses remain quite difficult to control for grasping and manipulation of daily life objects. The aim of the present observational case study is to document the kinematics of grasping in a group of 10 below-elbow amputated patients fitted with a myoelectric prosthesis in order to describe and better understand their compensatory strategies. They performed a grasping to lift task toward 3 objects (a mug, a cylinder and a cone) placed at two distances within the reaching area in front of the patients. The kinematics of the trunk and upper-limb on the non-amputated and prosthetic sides were recorded with 3 electromagnetic Polhemus sensors placed on the hand, the forearm (or the corresponding site on the prosthesis) and the ipsilateral acromion. The 3D position of the elbow joint and the shoulder and elbow angles were calculated thanks to a preliminary calibration of the sensor position. We examined first the effect of side, distance and objects with non-parametric statistics. Prosthetic grasping was characterized by severe temporo-spatial impairments consistent with previous clinical or kinematic observations. The grasping phase was prolonged and the reaching and grasping components uncoupled. The 3D hand displacement was symmetrical in average, but with some differences according to the objects. Compensatory strategies involved the trunk and the proximal part of the upper-limb, as shown by a greater 3D displacement of the elbow for close target and a greater forward displacement of the acromion, particularly for far targets. The hand orientation at the time of grasping showed marked side differences with a more frontal azimuth, and a more “thumb-up” roll. The variation of hand orientation with the object on the prosthetic side, suggested that the lack of finger and wrist mobility imposed some adaptation of hand pose relative to the object. The detailed kinematic analysis allows more insight into the mechanisms of the compensatory strategies that could be due to both increased distal or proximal kinematic constraints. A better knowledge of those compensatory strategies is important for the prevention of musculoskeletal disorders and the development of innovative prosthetics.

PMID:36399487 | DOI:10.1371/journal.pone.0277917

Am J Physiol Heart Circ Physiol. 2022 Nov 18. doi: 10.1152/ajpheart.00482.2022. Online ahead of print.

ABSTRACT

AIMS: This study compared differences in cardiovascular (CV) risk factor responses between males and females following endurance (END) and resistance (RES) training. We present the frequency of responders to each training modality, and the magnitude of response.

METHODS: Using a randomized cross-over design, 68 healthy adults (age: F: 24.5±4.6; M: 27.3±6.6) completed 3-months of RES and END, with 3-months washout. Peak oxygen consumption (VO₂peak), strength, body composition, blood pressure, glucose, insulin, and lipids were measured.

RESULTS: VO₂peak (L/min) significantly increased in both sexes following END, but not RES. The magnitude of change was larger in males (F: +0.20 L/min; M: +0.32 L/min), although this did not achieve statistical significance (P=0.051). Strength significantly increased in both sexes following RES (P<0.01), with a larger increase in males (Leg press: F: +39kg; M: +63kg; P<0.05). Lean mass significantly increased in both sexes (P<0.01) following RES and fat mass decreased in females following END (P=0.019). The change in C-reactive protein following END was significantly different between sexes (F: -0.4 mg/L; M: +0.5 mg/L; P=0.035). There were no differences between sexes in the proportion of individuals who responded positively to any variable following RES or END; differences between sexes were due to the magnitude of change.

CONCLUSIONS: Males had a larger increase in VO₂peak following END, and strength following RES. There were no sex differences in other CV risk factors. This suggests differences in physiological responses to strength and VO₂peak may not translate to changes in CV risk in healthy subjects.

PMID:36399383 | DOI:10.1152/ajpheart.00482.2022

J Med Internet Res. 2022 Nov 18;24(11):e39248. doi: 10.2196/39248.

ABSTRACT

BACKGROUND: An automated virtual reality cognitive therapy (gameChange) has demonstrated its effectiveness to treat agoraphobia in patients with psychosis, especially for high or severe anxious avoidance. Its economic value to the health care system is not yet established.

OBJECTIVE: In this study, we aimed to estimate the potential economic value of gameChange for the UK National Health Service (NHS) and establish the maximum cost-effective price per patient.

METHODS: Using data from a randomized controlled trial with 346 patients with psychosis (ISRCTN17308399), we estimated differences in health-related quality of life, health and social care costs, and wider societal costs for patients receiving virtual reality therapy in addition to treatment as usual compared with treatment as usual alone. The maximum cost-effective prices of gameChange were calculated based on UK cost-effectiveness thresholds. The sensitivity of the results to analytical assumptions was tested.

RESULTS: Patients allocated to gameChange reported higher quality-adjusted life years (0.008 QALYs, 95% CI -0.010 to 0.026) and lower NHS and social care costs (-£105, 95% CI -£1135 to £924) compared with treatment as usual (£1=US $1.28); however, these differences were not statistically significant. gameChange was estimated to be worth up to £341 per patient from an NHS and social care (NHS and personal social services) perspective or £1967 per patient from a wider societal perspective. In patients with high or severe anxious avoidance, maximum cost-effective prices rose to £877 and £3073 per patient from an NHS and personal social services perspective and societal perspective, respectively.

CONCLUSIONS: gameChange is a promising, cost-effective intervention for the UK NHS and is particularly valuable for patients with high or severe anxious avoidance. This presents an opportunity to expand cost-effective psychological treatment coverage for a population with significant health needs.

TRIAL REGISTRATION: ISRCTN Registry ISRCTN17308399; https://www.isrctn.com/ISRCTN17308399.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2019-031606.

PMID:36399379 | DOI:10.2196/39248

JMIR Public Health Surveill. 2022 Nov 18;8(11):e34908. doi: 10.2196/34908.

ABSTRACT

BACKGROUND: Peripheral arterial disease (PAD) causes blood vessel narrowing that decreases blood flow to the lower extremities, with symptoms such as leg pain, discomfort, and intermittent claudication. PAD increases risks for amputation, poor health-related quality of life, and mortality. It is estimated that more than 200 million people worldwide have PAD, although the paucity of PAD research in the East detracts from knowledge on global PAD epidemiology. There are few national data-based analyses or health care utilization investigations. Thus, a national data analysis of PAD incidence and prevalence would provide baseline data to enable health promotion strategies for patients with PAD.

OBJECTIVE: This study aims to identify South Korean trends in the incidence and prevalence of PAD and PAD treatment, in-hospital deaths, and health care utilization.

METHODS: This was a retrospective analysis of South Korean national claims data from 2009 to 2018. The incidence of PAD was determined by setting the years 2010 and 2011 as a washout period to exclude previously diagnosed patients with PAD. The study included adults aged ≥20 and <90 years who received a primary diagnosis of PAD between 2011 and 2018; patients were stratified according to age, sex, and insurance status for the incidence and prevalence analyses. Descriptive statistics were used to assess incidence, prevalence, endovascular revascularization (EVR) events, amputations, in-hospital deaths, and the health care utilization characteristics of patients with PAD.

RESULTS: Based on data from 2011 to 2018, there were an average of 124,682 and 993,048 incident and prevalent PAD cases, respectively, in 2018. PAD incidence (per 1000 persons) ranged from 2.68 to 3.09 during the study period. From 2012 to 2018, the incidence rate in both sexes showed an increasing trend. PAD incidence continued to increase with age. PAD prevalence (per 1000 persons) increased steadily, from 3.93 in 2011 to 23.55 in 2018. The number of EVR events varied between 933 and 1422 during the study period, and both major and minor amputations showed a decreasing trend. Health care utilization characteristics showed that women visited clinics more frequently than men, whereas men used tertiary and general hospitals more often than women.

CONCLUSIONS: The number of incident and prevalent PAD cases generally showed an increasing trend. Visits to tertiary and general hospitals were higher among men than women. These results indicate the need for attention not only to Western and male patients, but also to Eastern and female patients with PAD. The results are generalizable, as they are based on national claims data from the entire South Korean population, and they can promote preventive care and management strategies for patients with PAD in clinical and public health settings.

PMID:36399371 | DOI:10.2196/34908