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Nevin Manimala Statistics

Chemical Variability and Anti-inflammatory activity of Rosmarinus officinalis L. Leaf Essential Oil from Algerian Sahara

Chem Biodivers. 2024 Feb 22:e202302077. doi: 10.1002/cbdv.202302077. Online ahead of print.

ABSTRACT

The chemical composition of 71 oil samples from the leaves of Rosmarinus officinalis L., harvested in three provinces: Naâma (Western Algeria), Béchar and Adrar (Algerian Sahara), was investigated by GC-FID, GC/MS and 13 CNMR. In total, 52 compounds were identified accounting for 88.8 % to 99.9 % of the total composition. The chemical composition of the oils was largely dominated by monoterpenes, with 1,8-cineole (9.7-70.2 %), camphor (0.3-31.0 %) being the major compounds followed by borneol (0.3-21.0 %), α-pinene (4.5-14.5 %), β-pinene (0.1-12.0 %), linalool (0.7-9.9 %) and verbenone (up to 11.1 %) which was present only in the samples harvested in Adrar. All compositions (71 samples) were submitted to statistical analysis. Combination of hierarchical clustering dendrogram and principal component analysis suggested the existence of three groups (one of these being subdivided into two sub-groups) which were distinguished on the basis of 1,8-cineole, camphor and verbenone contents. Four essential oil samples, containing 1,8-cineole and/or camphor as main components, exhibited anti-inflammatory activity against lipoxygenase, with IC50 values in the range 93 to 155 μg/mL.

PMID:38388803 | DOI:10.1002/cbdv.202302077

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Nevin Manimala Statistics

Clinical implications of additional chromosomal abnormalities in adult acute myeloid leukemia with inv (16)/t(16;16)/CBFB::MYH11

Eur J Haematol. 2024 Feb 22. doi: 10.1111/ejh.14192. Online ahead of print.

ABSTRACT

OBJECTIVES: This study assesses the clinical significance of additional cytogenetic abnormalities (ACAs) and/or the deletion of 3’CBFB (3’CBFBdel ) resulting in unbalanced CBFB::MYH11 fusion in acute myeloid leukemia (AML) with inv (16)/t(16;16)/CBFB::MYH11.

METHODS: We retrospectively evaluated the clinicopathologic features of 47 adult de novo AML with inv (16)/t(16;16)/CBFB::MYH11 fusion. There were 44 balanced and 3 unbalanced CBFB::MYH11 fusions. Given the low frequency of unbalanced cases, the latter group was combined with 19 published cases (N = 22) for statistic and meta-analysis.

RESULTS: Both balanced and unbalanced cases were characterized by frequent ACAs (56.5% and 72.7%, respectively), with +8, +22, and del(7q) as the most frequent abnormalities. The unbalanced group tends to be younger individuals (p = .04) and is associated with a lower remission rate (p = .02), although the median overall survival (OS) was not statistically different (p = .2868). In the balanced group, “ACA” subgroup had higher mortality (p = .013) and shorter OS (p = .011), and patients with relapsed disease had a significantly shorter OS (p = .0011). Cox multivariate regression analysis confirmed that ACAs and history of disease relapse are independent risk factors, irrespective of disease relapse status. In the combined cohort, cases with ACAs had shorter OS than those with “Sole” abnormality (p = .0109).

CONCLUSIONS: ACAs are independent high-risk factors in adult AML with inv (16)/t(16;16)/CBFB::MYH11 fusion and should be integrated for risk stratification in this disease. Larger studies are needed to assess the clinical significance of the unbalanced CBFB::MYH11 fusion resulting from the 3’CBFBdel .

PMID:38388794 | DOI:10.1111/ejh.14192

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Nevin Manimala Statistics

Evaluation of Two Videos that Apply Evidence-Based Strategies to Increase Self-Efficacy and Reduce Opioid-Related Stigma Among Medical Students

Acad Psychiatry. 2024 Feb 22. doi: 10.1007/s40596-024-01945-3. Online ahead of print.

ABSTRACT

OBJECTIVE: This study evaluated the video-based application of evidence-based stigma reduction strategies to increase medical students’ screening-diagnostic self-efficacy for opioid use disorder (OUD) and reduce stigma toward opioid use.

METHODS: Formative qualitative research informed development of two videos for medical students. One uses an education strategy by including education regarding non-stigmatizing language use and OUD screening and diagnosis (Video A); the other uses an interpersonal contact strategy by presenting narratives regarding opioid use from three people who have a history of opioid use and three physicians (Video B). Both videos were administered to all respondents, with video order randomized. Effects on outcomes were evaluated using a pre-/post-test design with a 1-month follow-up. Participants also provided feedback on video content and design.

RESULTS: Medical students (N = 103) watched the videos and completed the pre-/post-test, with 99% (N = 102) completing follow-up 1 month after viewing both videos. Self-efficacy increased directly following viewing Video A, and this increase was sustained at 1-month follow-up. Stigma toward opioid use decreased directly following viewing Video B, and this decrease was sustained at 1-month follow-up for participants who watched Video B first. Statistically significant improvements were observed in most secondary outcomes (e.g., harm reduction acceptability) directly following watching each video and most were sustained at 1-month follow-up. Feedback about the videos suggested the delivery of evidence-based strategies in each video was appropriate.

CONCLUSIONS: Video-based applications of these evidence-based strategies were found acceptable by medical students and have potential to elicit sustained improvement in their screening-diagnostic self-efficacy and opioid-related stigma.

PMID:38388788 | DOI:10.1007/s40596-024-01945-3

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Nevin Manimala Statistics

Establishment and characterization of turtle liver organoids provides a potential model to decode their unique adaptations

Commun Biol. 2024 Feb 22;7(1):218. doi: 10.1038/s42003-024-05818-1.

ABSTRACT

Painted turtles are remarkable for their freeze tolerance and supercooling ability along with their associated resilience to hypoxia/anoxia and oxidative stress, rendering them an ideal biomedical model for hypoxia-induced injuries (including strokes), tissue cooling during surgeries, and organ cryopreservation. Yet, such research is hindered by their seasonal reproduction and slow maturation. Here we developed and characterized adult stem cell-derived turtle liver organoids (3D self-assembled in vitro structures) from painted, snapping, and spiny softshell turtles spanning ~175My of evolution, with a subset cryopreserved. This development is, to the best of our knowledge, a first for this vertebrate Order, and complements the only other non-avian reptile organoids from snake venom glands. Preliminary characterization, including morphological, transcriptomic, and proteomic analyses, revealed organoids enriched in cholangiocytes. Deriving organoids from distant turtles and life stages demonstrates that our techniques are broadly applicable to chelonians, permitting the development of functional genomic tools currently lacking in herpetological research. Such platform could potentially support studies including genome-to-phenome mapping, gene function, genome architecture, and adaptive responses to climate change, with implications for ecological, evolutionary, and biomedical research.

PMID:38388772 | DOI:10.1038/s42003-024-05818-1

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Do statins decrease testosterone in men? Systematic review and meta-analysis

Int Braz J Urol. 2024 Mar-Apr;50(2):119-135. doi: 10.1590/S1677-5538.IBJU.2023.0578.

ABSTRACT

PURPOSE: Statins are one of the most prescribed classes of drugs worldwide to treat hypercholesterolemia and dyslipidemia. By lowering the level of cholesterol, the use of statin could cause a reduction in testosterone levels. The objective was to evaluate whether the continued use of statins in patients with hypercholesterolemia causes a deficiency in testosterone and other sex hormones.

MATERIALS AND METHODS: Systematic Review with Meta-analysis, performed in Embase, Medline and Cochrane databases, until May 2023; PROSPERO CRD42021270424protocol. Selection performed by two independent authors with subsequent conference in stages. Methodology based on PRISMA statement. There were selected comparative studies, prospective cohorts (CP), randomized clinical trials (RCT) and cross-sectional studies (CSS) with comparison of testosterone levels before and after statin administration and between groups. Bias analysis were evaluated with Cochrane Tool, The Newcastle-Ottawa Scale (NOS), and using the Assess the Quality of Cross-sectional studies (AXIS) tool.

RESULTS: There were found on MedLine, Embase and Cochrane, after selected comparative studies, 10CP and 6RCT and 6CSS for the meta-analysis. In the Forrest plot with 6CSS, a correlation between patients with continuous use of statins and a reduction in total testosterone was evidenced with a statistically significant reduction of 55.02ng/dL (95%CI=[39.40,70.64],I²=91%,p<0.00001).In the analysis with 5RCT, a reduction in the mean total testosterone in patients who started continuous statin use was evidenced, with a statistical significance of 13.12ng/dL (95%CI=[1.16,25.08],I²=0%,p=0.03). Furthermore, the analysis of all prospective studies with 15 articles showed a statistically significant reduction in the mean total testosterone of 9.11 ng/dL (95%CI=[0.16,18.06],I²=37%,p=0.04). A reduction in total testosterone has been shown in most studies and in its accumulated analysis after statin use. However, this decrease was not enough to reach levels below normal.

CONCLUSION: Statins use causes a decrease in total testosterone, not enough to cause a drop below the normal range and also determines increase in FSH levels. No differences were found in LH, Estradiol, SHBG and Free Testosterone analysis.

PMID:38386784 | DOI:10.1590/S1677-5538.IBJU.2023.0578

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Women’s Experiences with Digital Breast Tomosynthesis and Targeted Breast Ultrasound for Focal Breast Complaints: A Survey Study

J Womens Health (Larchmt). 2024 Feb 21. doi: 10.1089/jwh.2023.0502. Online ahead of print.

ABSTRACT

Background: Owing to its high sensitivity, as concluded in the Breast UltraSound Trial (BUST), targeted ultrasound (US) now seems a promising accurate stand-alone modality for diagnostic evaluation of breast complaints. This approach implies omission of bilateral digital breast tomosynthesis (DBT) in women with clearly benign US findings. Within BUST, radiologists started with US followed by DBT. This side-study investigates women’s experiences with DBT, their main motivation to undergo diagnostic imaging, and their view on US as a stand-alone modality. Methods: A subset of BUST participants completed a questionnaire on their DBT experiences, reason for undergoing diagnostic assessment, and view on US-only diagnostics. Responses were analyzed with descriptive statistics and logistic regression analyses. Results: In total, 778 of 838 women (response rate 92.8%) were included (M = 47, SD = 11.16). Of them, 16.8% reported no burden of DBT, 33.5% slight burden, 31.0% moderate, and 12.7% severe burden. Furthermore, 13% reported no pain, 35.3% slight pain, 33.2% moderate, and 11.3% severe pain. Moreover, 88.3% indicated that the most important reason for breast assessment was explanation of their complaint and to rule out breast cancer, whereas 3.2% wanted to “check” both breasts. And 82.4% reported satisfaction with US only in case of a nonmalignancy. Conclusions: Our study shows that most women in the diagnostic setting experience at least slight-to-moderate DBT-related burden and pain, and that explanation for their symptoms is their main interest. Also, the majority report satisfaction with US only in case of nonmalignant findings. However, exploration of women’s perspectives outside this study is needed as our participants all underwent both examinations.

PMID:38386779 | DOI:10.1089/jwh.2023.0502

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Nevin Manimala Statistics

A Turing test of whether AI chatbots are behaviorally similar to humans

Proc Natl Acad Sci U S A. 2024 Feb 27;121(9):e2313925121. doi: 10.1073/pnas.2313925121. Epub 2024 Feb 22.

ABSTRACT

We administer a Turing test to AI chatbots. We examine how chatbots behave in a suite of classic behavioral games that are designed to elicit characteristics such as trust, fairness, risk-aversion, cooperation, etc., as well as how they respond to a traditional Big-5 psychological survey that measures personality traits. ChatGPT-4 exhibits behavioral and personality traits that are statistically indistinguishable from a random human from tens of thousands of human subjects from more than 50 countries. Chatbots also modify their behavior based on previous experience and contexts “as if” they were learning from the interactions and change their behavior in response to different framings of the same strategic situation. Their behaviors are often distinct from average and modal human behaviors, in which case they tend to behave on the more altruistic and cooperative end of the distribution. We estimate that they act as if they are maximizing an average of their own and partner’s payoffs.

PMID:38386710 | DOI:10.1073/pnas.2313925121

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Nevin Manimala Statistics

Perturbative diffraction methods resolve a conformational switch that facilitates a two-step enzymatic mechanism

Proc Natl Acad Sci U S A. 2024 Feb 27;121(9):e2313192121. doi: 10.1073/pnas.2313192121. Epub 2024 Feb 22.

ABSTRACT

Enzymes catalyze biochemical reactions through precise positioning of substrates, cofactors, and amino acids to modulate the transition-state free energy. However, the role of conformational dynamics remains poorly understood due to poor experimental access. This shortcoming is evident with Escherichia coli dihydrofolate reductase (DHFR), a model system for the role of protein dynamics in catalysis, for which it is unknown how the enzyme regulates the different active site environments required to facilitate proton and hydride transfer. Here, we describe ligand-, temperature-, and electric-field-based perturbations during X-ray diffraction experiments to map the conformational dynamics of the Michaelis complex of DHFR. We resolve coupled global and local motions and find that these motions are engaged by the protonated substrate to promote efficient catalysis. This result suggests a fundamental design principle for multistep enzymes in which pre-existing dynamics enable intermediates to drive rapid electrostatic reorganization to facilitate subsequent chemical steps.

PMID:38386706 | DOI:10.1073/pnas.2313192121

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Nevin Manimala Statistics

SWOG S1820: A pilot randomized trial of the Altering Intake, Managing Bowel Symptoms Intervention in Survivors of Rectal Cancer

Cancer. 2024 Feb 22. doi: 10.1002/cncr.35264. Online ahead of print.

ABSTRACT

BACKGROUND: Survivors of rectal cancer experience persistent bowel dysfunction after treatments. Dietary interventions may be an effective approach for symptom management and posttreatment diet quality. SWOG S1820 was a pilot randomized trial of the Altering Intake, Managing Symptoms in Rectal Cancer (AIMS-RC) intervention for bowel dysfunction in survivors of rectal cancer.

METHODS: Ninety-three posttreatment survivors were randomized to the AIMS-RC group (N = 47) or the Healthy Living Education attention control group (N = 46) after informed consent and completion of a prerandomization run-in. Outcome measures were completed at baseline and at 18 and 26 weeks postrandomization. The primary end point was total bowel function score, and exploratory end points included low anterior resection syndrome (LARS) score, quality of life, dietary quality, motivation, self-efficacy, and positive/negative affect.

RESULTS: Most participants were White and college educated, with a mean age of 55.2 years and median time since surgery of 13.1 months. There were no statistically significant differences in total bowel function score by group, with the AIMS-RC group demonstrating statistically significant improvements in the exploratory end points of LARS (p = .01) and the frequency subscale of the bowel function index (p = .03). The AIMS-RC group reported significantly higher acceptability of the study.

CONCLUSIONS: SWOG S1820 did not provide evidence of benefit from the AIMS-RC intervention relative to the attention control. Select secondary end points did demonstrate improvements. The study was highly feasible and acceptable for participants in the National Cancer Institute Community Oncology Research Program. Findings provide strong support for further refinement and effectiveness testing of the AIMS-RC intervention.

PMID:38386696 | DOI:10.1002/cncr.35264

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Age-dependent ventilator-induced lung injury: Mathematical modeling, experimental data, and statistical analysis

PLoS Comput Biol. 2024 Feb 22;20(2):e1011113. doi: 10.1371/journal.pcbi.1011113. Online ahead of print.

ABSTRACT

A variety of pulmonary insults can prompt the need for life-saving mechanical ventilation; however, misuse, prolonged use, or an excessive inflammatory response, can result in ventilator-induced lung injury. Past research has observed an increased instance of respiratory distress in older patients and differences in the inflammatory response. To address this, we performed high pressure ventilation on young (2-3 months) and old (20-25 months) mice for 2 hours and collected data for macrophage phenotypes and lung tissue integrity. Large differences in macrophage activation at baseline and airspace enlargement after ventilation were observed in the old mice. The experimental data was used to determine plausible trajectories for a mathematical model of the inflammatory response to lung injury which includes variables for the innate inflammatory cells and mediators, epithelial cells in varying states, and repair mediators. Classification methods were used to identify influential parameters separating the parameter sets associated with the young or old data and separating the response to ventilation, which was measured by changes in the epithelial state variables. Classification methods ranked parameters involved in repair and damage to the epithelial cells and those associated with classically activated macrophages to be influential. Sensitivity results were used to determine candidate in-silico interventions and these interventions were most impact for transients associated with the old data, specifically those with poorer lung health prior to ventilation. Model results identified dynamics involved in M1 macrophages as a focus for further research, potentially driving the age-dependent differences in all macrophage phenotypes. The model also supported the pro-inflammatory response as a potential indicator of age-dependent differences in response to ventilation. This mathematical model can serve as a baseline model for incorporating other pulmonary injuries.

PMID:38386693 | DOI:10.1371/journal.pcbi.1011113