Nevin Manimala

Gait Posture. 2021 Sep 24;90:441-448. doi: 10.1016/j.gaitpost.2021.09.194. Online ahead of print.

ABSTRACT

AIM: To determine whether a running intervention utilising plyometric activities improved leg stiffness in youth with cerebral palsy (CP), GMFCS levels I and II.

METHOD: This stratified randomised controlled trial examined the lower limb kinetics and kinematics of a sample of youths with CP during sub-maximal hopping and running, prior to and immediately following a 12-week running intervention that incorporated low load plyometric training. Included participants were 13 in the control group (mean age 13 years 2 months [SD 2 years 7 months]; six males; nine GMFCS level I; six unilateral) and 18 in the intervention group (mean age 12 years 9 months [SD 2 years 10 months]; 13 males; 11 GMFCS level I; nine unilateral). Derived variables included three-dimensional leg stiffness as well as resultant ground reaction force and change in leg length. Generalised linear mixed models were developed for statistical analysis.

RESULTS: At follow-up the intervention group had greater leg stiffness than the control group during submaximal hopping (Intervention median = 3278Nm^-1; Control median = 1556Nm^-1; p < 0.01). At follow-up, participants in the intervention group in GMFCS Level I had greater leg stiffness than the control group during jogging (Intervention mean=38.84 (SD=25.55); Control mean=29.38 (SD=11.11); t = 2.61 p = 0.01).

INTERPRETATION: A running training intervention which includes plyometric activities can improve leg stiffness in young people with CP, especially those in GMFCS level I.

PMID:34600178 | DOI:10.1016/j.gaitpost.2021.09.194

Mar Pollut Bull. 2021 Sep 29;173(Pt A):112983. doi: 10.1016/j.marpolbul.2021.112983. Online ahead of print.

ABSTRACT

In this study, we determined the spatial variations and potential risks of heavy metals in the sediments of Yueqing Bay by assessing the relationship between metal concentrations and sediment physiochemical factors. We found higher sediment metal concentrations in the inner bay than in the central and outer bay, particularly with respect to Hg, Cu, and Pb concentrations. According to the sediment quality guidelines, the heavy metals had a toxicity incidence probability of 21%. Assessments of heavy metal contamination using the geo-accumulation index and potential ecological risk index suggest that Cr, As, Pb, and Hg likely pose low ecological risks, while Cu, Zn, and Cd were identified as priority pollutants and may pose moderate ecological risks to the ecosystem. Multivariate statistical analysis inferred the high influence of sediment texture, total organic carbon (TOC), and petroleum hydrocarbons (PHCs) on the distribution and fate of metals in sediment.

PMID:34600167 | DOI:10.1016/j.marpolbul.2021.112983

J Proteomics. 2021 Sep 29:104386. doi: 10.1016/j.jprot.2021.104386. Online ahead of print.

ABSTRACT

Quantitative label-free mass spectrometry (MS) is an increasingly powerful technology for profiling thousands of proteins from complex biological samples. One of the primary goals of analyses performed on such proteomics data is to detect differentially expressed proteins (DEPs) under different experimental conditions. Many statistical methods have been developed and assessed for DEP detection in various proteomics studies. However, it remains a challenge for many proteomics scientists to choose an appropriate statistical procedure. Therefore, in this study, we organized 12 common testing algorithms and 6 P-value combination methods and further provided Cohen’s d effect size for every protein and three evaluation criteria to help proteomics scientists investigate their influence on DEP detection in a systematic manner. To promote the widespread use of these methods, we developed a user-friendly web tool, StatsPro, and presented two case studies involving label-free quantitative proteomics data obtained using data-dependent acquisition and data-independent acquisition to illustrate its practicability. This tool is freely available in our GitHub repository (https://github.com/YanglabWCH/StatsPro/). SIGNIFICANCE: One of the primary goals of analyses performed on liquid chromatography-mass spectrometry (LC-MS) based proteomics data is to detect differentially expressed proteins (DEPs) under different experimental conditions. Despite of many research efforts have been proposed to detect DEPs, to date, there is a scarcity of efficient, systematic, and easy-to-handle tools that are tailored for proteomics scientists to choose an appropriate statistical procedure. Herein, we present a new tool, StatsPro, to enable implementation and evaluation of different statistical methods for proteomics scientists. This tool has two significant advances compared to existing software: a) It integrates up to 18 common statistical approaches (12 statistical tests and 6 P-value combination strategies) and performs Cohen’s d effect size systematically for users, moreover, it provides a web-based interface and can be quite conveniently operated by users, even those with less profound computational background. b) It supports three performance evaluation criteria (e.g. number of DEPs, correlation coefficient between P-values and effect sizes, Area under the ROC curve) for users to review the final statistical results, which may guide the method selection for DEPs detection.

PMID:34600153 | DOI:10.1016/j.jprot.2021.104386

J Struct Biol. 2021 Sep 29:107800. doi: 10.1016/j.jsb.2021.107800. Online ahead of print.

ABSTRACT

The flux of ions and molecules in and out of the cell is vital for maintaining the basis of various biological processes. The permeation of substrates across the cellular membrane is mediated through the function of specialized integral membrane proteins commonly known as membrane transporters. These proteins undergo a series of structural rearrangements that allow a primary substrate binding site to be accessed from either side of the membrane at a given time. Structural insights provided by experimentally resolved structures of membrane transporters have aided in the biophysical characterization of these important molecular drug targets. However, characterizing the transitions between conformational states remains challenging to achieve both experimentally and computationally. Though molecular dynamics simulations are a powerful approach to provide atomistic resolution of protein dynamics, a recurring challenge is its ability to efficiently obtain relevant timescales of large conformational transitions as exhibited in transporters. One approach to overcome this difficulty is to adaptively guide the simulation to favor exploration of the conformational landscape, otherwise known as adaptive sampling. Furthermore, such sampling is greatly benefited by the statistical analysis of Markov state models. Historically, the use of Markov state models has been effective in quantifying slow dynamics or long timescale behaviors such as protein folding. Here, we review recent implementations of adaptive sampling and Markov state models to not only address current limitations of molecular dynamics simulations, but to also highlight how Markov state modeling can be applied to investigate the structure-function mechanisms of large, complex membrane transporters.

PMID:34600140 | DOI:10.1016/j.jsb.2021.107800

Endocr Pract. 2021 Sep 29:S1530-891X(21)01240-4. doi: 10.1016/j.eprac.2021.09.010. Online ahead of print.

ABSTRACT

OBJECTIVE: The Alertgy noninvasive continuous glucose monitor (ANICGM) is a novel wristband device that reports glucose levels without entailing skin puncture. This study evaluated the performance of the ANICGM compared with an FDA-approved glucose meter in patients with type 2 diabetes.

METHODS: The ANICGM device measures changes in the electromagnetic field generated by its sensor to produce a dielectric spectrum. The data contained within this spectrum are used in tandem with machine learning algorithms to estimate blood glucose (BG). Values from the ANICGM were collected, sent to the Alertgy lab, formatted, and compared to fingerstick BG measured using the Accuchek Inform II glucometer. Fifteen patients completed three 120-minute sessions. Mean absolute relative difference (MARD) was calculated.

RESULTS: MARD values were compared for study Days 2 and 3. The MARD for Day 2 was 18.5% (95% CI: 12.8, 42.2%), and the MARD for Day 3 was 15.3% (95% CI: 12.3,18.4%). The difference in MARD between the two days was not statistically significant (P=0.210).

CONCLUSIONS: The result MARDs suggest that further investigation into the use of dielectric spectroscopy for glucose monitoring should be explored.

PMID:34600130 | DOI:10.1016/j.eprac.2021.09.010

Int J Surg. 2021 Sep 29:106135. doi: 10.1016/j.ijsu.2021.106135. Online ahead of print.

ABSTRACT

BACKGROUND: To summarize the current evidence on different laser-based enucleation techniques for benign prostate hyperplasia and compare the efficacy and safety of en-bloc, two-lobe and three-lobe techniques.

MATERIALS AND METHODS: Through a systematical search of multiple scientific databases in March 2021, we performed a systematic review and cumulative meta-analysis of the primary outcomes of interest according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (Assessing the methodological quality of systematic reviews) Guidelines, whose protocol was registered with PROSPERO(CRD42021240684).

RESULTS: A total of 9 studies were included. All three laser enucleation techniques had no statistically significant difference in terms of enucleated prostate weight, maximum urinary flow rate (Qmax), postvoid residual urine volume (PVR), international prostate symptom score (IPSS), transient UI (TUI), persistent UI (PUI) and early postoperative complications. A shorter enucleation time was associated with the en-bloc technique compared to three technique(MD: 8.26,95%CI: 12.73∼-3.79, p = 0.0003), whereas no significant difference was found in en-bloc versus two-lobe technique(MD:0.97,95%CI: 0.30-2.24,p = 0.13) and two-lobe versus three-lobe technique(MD: 3.19,95%CI: 7.45-1.06, p = 0.14). A higher enucleation rate was associated with the en-bloc and two-lobe technique (MD:0.05,95%CI: 0.00-0.10, p = 0.03; MD:0.09, 95%CI: 0.01-0.17, p = 0.03, respectively). A superior QoL was related to the two-lobe enucleation technique compared to three-lobe technique(MD:0.22,95%CI:0.06-0.39, p = 0.009), whereas no meaningful difference was found in the group of en-bloc versus two-lobe(MD: 0.12,95%CI: 0.62-0.37, p = 0.62) and group of en-bloc versus three-lobe(MD: 0.14, 95%CI: 0.56-0.29, p = 0.52).

CONCLUSIONS: En-bloc and two-lobe laser-based enucleation techniques are feasible and safe alternative to three-lobe technique with comparable surgical outcomes and similar functional outcomes. A superior enucleation efficiency was associated with En-bloc and the two-lobe techniques compared to the three-lobe technique.

PMID:34600125 | DOI:10.1016/j.ijsu.2021.106135

Transpl Immunol. 2021 Sep 29:101475. doi: 10.1016/j.trim.2021.101475. Online ahead of print.

ABSTRACT

OBJECTIVE: This study was conducted to investigate the effect of social support on psychological resilience in liver transplant patients receiving immunosuppression therapy.

METHOD: This study was carried out as a descriptive and cross-sectional study with the participation of 290 liver transplant patients hospitalized in the liver transplant center of a research and application hospital. Personal Information Form, Multidimensional Scale of Perceived Social Support (MSPSS) and Brief Resilience Scale (BRS) were used in data collection. The data analysis was performed with IBM Statistical Package for the Social Sciences Statistics 25.

RESULTS: According to the data obtained, it was determined that 30.4% of the patients were 58 years old and over, 81% of them were male and 92.8% of them were married. It was found that all of the patients used antimetabolites and corticosteroids, and 82.8% of them used calcineurin inhibitors. It was determined that 32.8% of the patients experienced infection, neuropsychiatric problems and nephrotoxicity at the same time. The psychological resilience of the patients was found to be moderate, and their perceived social support was found to be low.

CONCLUSION: It is not always possible for liver transplant patients to deal with their situation effectively. The psychological resilience and social support levels of patients who have undergone liver transplantation should be noticed, and social, economic and psychological support should be provided.

PMID:34600070 | DOI:10.1016/j.trim.2021.101475

Biol Chem. 2021 Oct 4. doi: 10.1515/hsz-2021-0314. Online ahead of print.

ABSTRACT

Periportal and perivenous hepatocytes show zonal heterogeneity in metabolism and signaling. Here, hepatic zonation in mouse liver was analyzed by non-targeted mass spectrometry (MS) and by the antibody-based DigiWest technique, yielding a comprehensive overview of protein expression in periportal and perivenous hepatocytes. Targeted immunoaffinity-based proteomics were used to substantiate findings related to drug metabolism. 165 (MS) and 82 (DigiWest) zonated proteins were identified based on the selected criteria for statistical significance, including 7 (MS) and 43 (DigiWest) proteins not identified as zonated before. New zonated proteins especially comprised kinases and phosphatases related to growth factor-dependent signaling, with mainly periportal localization. Moreover, the mainly perivenous zonation of a large panel of cytochrome P450 enzymes was characterized. DigiWest data were shown to complement the MS results, substantially improving possibilities to bioinformatically identify zonated biological processes. Data mining revealed key regulators and pathways preferentially active in either periportal or perivenous hepatocytes, with β-catenin signaling and nuclear xeno-sensing receptors as the most prominent perivenous regulators, and several kinase- and G-protein-dependent signaling cascades active mainly in periportal hepatocytes. In summary, the present data substantially broaden our knowledge of hepatic zonation in mouse liver at the protein level.

PMID:34599868 | DOI:10.1515/hsz-2021-0314

Brain Behav. 2021 Oct 2. doi: 10.1002/brb3.2303. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the ability of persons with metastatic cancer to self-assess their medical decision-making capacity (MDC). To investigate this, we compared an objective measure of MDC with self-ratings and evaluated predictors of agreement.

METHODS: Data were obtained from a cross-sectional study of metastatic cancer patients at a large academic medical center. Across all standards of MDC, sensitivity, specificity, and reliability using Gwet’s AC1 statistic were calculated using the objective measure as the gold standard. Logistic regression was used to evaluate predictors of agreement between the measures across all MDC standards.

RESULTS: In those with brain metastases, high sensitivity (greater than 0.7), but low specificity was observed for all standards. Poor reliability was observed across all standards. Higher age resulted in higher odds of disagreement for Standard 3 (appreciation) (OR: 1.07, 95% CI: 1.00, 1.15) and Standard 4 (reasoning) (OR: 1.05, 95% CI: 1.00, 1.10). For Standard 3, chemotherapy use and brain metastases compared to other metastases resulted in higher odds of disagreement (Chemotherapy: OR: 5.62, 95% CI: 1.37, 23.09, Brain Metastases: OR: 5.93, 95% CI: 1.28, 27.55). For Standard 5 (understanding), no predictors were associated with disagreement.

CONCLUSIONS: For less cognitively complex standards (e.g., appreciation), self-report may be more valid and reliable than more cognitively complex standards (e.g., reasoning or understanding). However, overall, MDC self-report in the current sample is suboptimal. Thus, the need for detailed assessment of MDC, especially when patients are older or used chemotherapy, is indicated. Other studies should be conducted to assess MDC agreement longitudinally.

PMID:34599852 | DOI:10.1002/brb3.2303

Rheumatology (Oxford). 2021 Oct 2:keab733. doi: 10.1093/rheumatology/keab733. Online ahead of print.

ABSTRACT

OBJECTIVES: Joint replacement due to end-stage osteoarthritis (OA) has been linked to incidence of several cancers. We aimed to estimate the association between newly diagnosed knee and hip OA and incidence of nine common cancer types.

METHODS: We identified persons with incident knee or hip OA, aged ≥40 years, between 2009 and 2015 in the SIDIAP database in Catalonia, Spain. We matched up to 3 OA-free controls on age, sex and general practitioner. We followed participants from 1 year after OA diagnosis until migration, death, end of study at Dec 31st 2017 or incident cancer of: stomach, colorectal, liver, pancreas, lung, skin, breast, prostate, and bladder. We used flexible parametric survival models, adjusted for confounders. Estimates were corrected for misclassification using probabilistic bias analysis.

RESULTS: We included 117 750 persons with knee OA and matched 309 913 persons without, with mean (SD) age of 67.5 (11.1) years and 63% women. The hip cohort consisted of 39 133 persons with hip OA and 116 713 controls. For most of included cancers, the hazard ratios (HRs) were close to 1. The HR of lung cancer for knee OA exposure was 0.80 (95%CI 0.71, 0.89) and attenuated to 0.98 (0.76, 1.27) in non-smokers. The hazard of colorectal cancer was lower in persons with both knee and hip OA by 10-20%.

CONCLUSIONS: Knee and hip OA are not associated with studied incident cancers, apart from lower risk of colorectal cancer. The often-reported protective association of knee OA with lung cancer is explained by residual confounding.

PMID:34599812 | DOI:10.1093/rheumatology/keab733