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Nevin Manimala Statistics

Isolated, displaced, talar body fracture: a case report and literature review

Acta Biomed. 2023 Jul 24;94(S1):e2023205. doi: 10.23750/abm.v94iS1.14198.

ABSTRACT

Talar body fractures are uncommon fractures of the foot and its management results to be very hard due to retrograde vascularization and wide articular cartilage coverage of talar surface, which could easily lead to poor functional outcomes, avascular osteonecrosis and early post traumatic arthritis. We describe a case of displaced, vertical, talar body fracture in a 41-year-old patient treated with reduction and fixation by talar anteromedial approach coupled to medial malleolar osteotomy to better expose the fracture. Our literature review has found few studies, in addition with a low level of statistical evidence. We advocate for more studies with a bigger sample and with a design of randomized control trials.

PMID:37486598 | DOI:10.23750/abm.v94iS1.14198

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Dereplication of Lantana trifolia L. leaves and fruits by UFLC-DAD-(+)-ESI-MS/MS and its antifungal and cytotoxic activities

Metabolomics. 2023 Jul 24;19(8):68. doi: 10.1007/s11306-023-02032-8.

ABSTRACT

INTRODUCTION: Lantana trifolia L. (Verbenaceae) is a shrubby plant. In folk medicine, its leaves are used in the form of infusions and syrups to treat angina, coughs, and colds; they are also applied as tranquilizer. Previous studies have reported the antimicrobial potential of the compounds present in L. trifolia leaves.

OBJECTIVES: To report the anti-Candida activities of the fractions obtained from the fruits and leaves of two L. trifolia specimens.

METHODS: The L. trifolia fractions were submitted to UFLC-DAD-(+)-ESI-MS/MS, and the data were analyzed by using multivariate statistical tools (PCA, PLS-DA) and spectral similarity analyses based on molecular networking, which aided dereplication of the bioactive compounds. Additionally, NMR analyses were performed to confirm the chemical structure of some of the major compounds in the fractions.

RESULTS: The ethyl acetate fractions presented MIC values lower than 100 µg mL-1 against the three Candida strains evaluated herein (C. albicans, C. tropicalis, and C. glabrata). Fractions FrPo AcOEt, FrPe AcOEt, and FrPe nBut had MIC values of 1.46, 2.93, and 2.93 µg mL-1 against C. glabrata, respectively. These values resembled the MIC value of amphotericin B, the positive control (0.5-1.0 µg mL-1), against this same strain. Cytotoxicity was measured and used to calculate the selectivity index.

CONCLUSION: On the basis of our data, the most active fractions in the antifungal assay were more selective against C. glabrata than against non-infected cells. The analytical approach adopted here allowed us to annotate 29 compounds, nine of which were bioactive (PLS-DA results) and belong to the class of phenolic compounds.

PMID:37486581 | DOI:10.1007/s11306-023-02032-8

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Impact of COVID-19 and effects of booster vaccination with BNT162b2 on six-month long COVID symptoms, quality of life, work productivity and activity impairment during Omicron

J Patient Rep Outcomes. 2023 Jul 24;7(1):77. doi: 10.1186/s41687-023-00616-5.

ABSTRACT

BACKGROUND: Longitudinal estimates of long COVID burden during Omicron remain limited. This study characterized long-term impacts of COVID-19 and booster vaccination on symptoms, Health-Related Quality of Life (HRQoL), and Work Productivity Activity Impairment (WPAI).

METHODS: Outpatients with ≥ 1 self-reported symptom and positive SARS-CoV-2 test at CVS Health United States test sites were recruited between 01/31 and 04/30/2022. Symptoms, EQ-5D and WPAI were collected via online surveys until 6 months following infection. Both observed and model-based estimates were analyzed. Effect sizes based on Cohen’s d quantified the magnitude of outcome changes over time, within and between vaccination groups. Mixed models for repeated measures were conducted for multivariable analyses, adjusting for covariates. Logistic regression assessed odds ratio (OR) of long COVID between vaccination groups.

RESULTS: At long COVID start (Week 4), 328 participants included 87 (27%) Boosted with BNT162b2, 86 (26%) with a BNT162b2 primary series (Primed), and 155 (47%) Unvaccinated. Mean age was 42.0 years, 73.8% were female, 26.5% had ≥ 1 comorbidity, 36.9% prior infection, and 39.6% reported ≥ 3 symptoms (mean: 3.1 symptoms). At Month 6, among 260 participants, Boosted reported a mean of 1.1 symptoms versus 3.4 and 2.8 in Unvaccinated and Primed, respectively (p < 0.001). Boosted had reduced risks of ≥ 3 symptoms versus Unvaccinated (observed: OR 0.22, 95% CI 0.10-0.47, p < 0.001; model-based: OR 0.36, 95% CI 0.15-0.87, p = 0.019) and Primed (observed: OR 0.29, 95% CI 0.13-0.67, p = 0.003; model-based: OR 0.59, 95% CI 0.21-1.65, p = 0.459). Results were consistent using ≥ 2 symptoms. Regarding HRQoL, among those with long COVID, Boosted had higher EQ-5D Utility Index (UI) than Unvaccinated (observed: 0.922 vs. 0.731, p = 0.014; model-based: 0.910 vs. 0.758, p-value = 0.038) and Primed (0.922 vs. 0.648, p = 0.014; model-based: 0.910 vs. 0.708, p-value = 0.008). Observed and model-based estimates for EQ-VAS and UI among Boosted were comparable with pre-COVID since Month 3. Subjects vaccinated generally reported better WPAI scores.

CONCLUSIONS: Long COVID negatively impacted HRQoL and WPAI. The BNT162b2 booster could have a beneficial effect in reducing the risk and burden of long COVID. Boosted participants reported fewer and less durable symptoms, which contributed to improve HRQoL and maintain WPAI levels. Limitations included self-reported data and small sample size for WPAI.

PMID:37486567 | DOI:10.1186/s41687-023-00616-5

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HN-CLEAR: Head and Neck Consensus Language for Ease and Reproducibility, a Multidisciplinary Consensus Mechanism for Head and Neck Pathology

Head Neck Pathol. 2023 Jul 24. doi: 10.1007/s12105-023-01570-w. Online ahead of print.

NO ABSTRACT

PMID:37486534 | DOI:10.1007/s12105-023-01570-w

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Prediction of Intracranial Temperature Through Invasive and Noninvasive Measurements on Patients with Severe Traumatic Brain Injury

Adv Exp Med Biol. 2023;1424:255-263. doi: 10.1007/978-3-031-31982-2_29.

ABSTRACT

The brain’s temperature measurements (TB) in patients with severe brain damage are important, in order to offer the optimal treatment. The purpose of this research is the creation of mathematical models for the TB‘s prediction, based on the temperatures in the bladder (TBL), femoral artery (TFA), ear canal (TΕC), and axilla (TA), without the need for placement of intracranial catheter, contributing significantly to the research of the human thermoregulatory system.The research involved 18 patients (13 men and 5 women), who were hospitalized in the adult intensive care units (ICU) of Larissa’s two hospitals, with severe brain injury. An intracranial catheter with a thermistor was used to continuously measure TB and other parameters. The TB‘s measurements, and simultaneously one or more of TBL, TFA, TEC, and TA, were recorded every 1 h.To create TB predicting models, the data of each measurement was separated into (a) model sample (measurements’ 80%) and (b) validation sample (measurements’ 20%). Multivariate linear regression analysis demonstrated that it is possible to predict brain’s temperature (PrTB), using independent variables (R2 was TBL = 0.73, TFA = 0.80, TEC = 0.27, and TA = 0.17, p < 0.05). Significant linear associations were found, statistically, and no difference in means between TB and PrTB of each prediction model. Also, the 95% limits of agreement and the percent coefficient of variation showed sufficient agreement between the TB and PrTB in each prediction model.In conclusion, brain’s temperature prediction models based on TBL, TFA, TEC, and TA were successful. Its determination contributes to the improvement of clinical decision-making.

PMID:37486502 | DOI:10.1007/978-3-031-31982-2_29

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3D QSAR based Virtual Screening of Flavonoids as Acetylcholinesterase Inhibitors

Adv Exp Med Biol. 2023;1424:233-240. doi: 10.1007/978-3-031-31982-2_26.

ABSTRACT

In an attempt to develop therapeutic agents to treat Alzheimer’s disease, a series of flavonoid analogues were collected, which already had established acetylcholinesterase (AChE) enzyme inhibition activity. For each molecule we also collected biological activity data (Ki). Then, 3D-QSAR (quantitative structure-activity relationship model) was developed which showed acceptable predictive and descriptive capability as represented by standard statistical parameters r2 and q2. This SAR data can explain the key descriptors which can be related to AChE inhibitory activity. Using the QSAR model, pharmacophores were developed based on which, virtual screening was done and a dataset was obtained which loaded as a prediction set to fit the developed QSAR model. Top 10 compounds fitting the QSAR model were subjected to molecular docking. CHEMBL1718051 was found to be the lead compound. This study is offering an example of a computationally-driven tool for prioritisation and discovery of probable AChE inhibitors. Further, in vivo and in vitro testing will show its therapeutic potential.

PMID:37486499 | DOI:10.1007/978-3-031-31982-2_26

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Signature-Based Computational Drug Repurposing for Amyotrophic Lateral Sclerosis

Adv Exp Med Biol. 2023;1424:201-211. doi: 10.1007/978-3-031-31982-2_22.

ABSTRACT

Amyotrophic lateral sclerosis (ALS) is a late-onset fatal neurodegenerative disease characterized by progressive loss of the upper and lower motor neurons. There are currently limited approved drugs for the disorder, and for this reason the strategy of repositioning already approved therapeutics could exhibit a successful outcome. Herein, we used CMAP and L1000CDS2 databases which include gene expression profiles datasets (genomic signatures) to identify potent compounds and classes of compounds which reverse disease’s signature which could in turn reverse its phenotype. ALS signature was obtained by comparing gene expression of muscle biopsy specimens between diseased and healthy individuals. Statistical analysis was conducted to explore differentially transcripts in patients’ samples. Then, the list of upregulated and downregulated genes was used to query both databases in order to determine molecules which downregulate the genes which are upregulated by ALS and vice versa. These compounds, based on their chemical structure along with known treatments, were clustered to reveal drugs with novel and potentially more effective mode of action with most of them predicted to affect pathways heavily involved in ALS. This evidence suggests that these compounds are strong candidates for moving to the next phase of the drug repurposing pipeline which is in vitro and in vivo experimental evaluation.

PMID:37486495 | DOI:10.1007/978-3-031-31982-2_22

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A Retrospective Analysis to Investigate Contact Sensitization in Greek Population Using Classic and Machine Learning Techniques

Adv Exp Med Biol. 2023;1424:145-155. doi: 10.1007/978-3-031-31982-2_15.

ABSTRACT

Allergic contact dermatitis (ACD) is an inflammatory reaction affecting all age groups and both sexes. ACD is characterized by a delayed-type hypersensitivity reaction IV caused by skin contact with haptens. Chronic exposure typically leads to a decrease in erythema accompanied by lichenification (thickening and hardening of the skin) and persistent itching. The current study aims to investigate the patterns of contact sensitization in the Greek population using patch test data analysis. Patch test data from 240 patients (120 Males/120 Females) with allergic contact dermatitis were collected at the Laboratory for Patch Testing, National Reference Center for Occupational Dermatoses “Andreas Syggros” Hospital in Athens Greece. The contact allergic reactions were caused by ethylenediamine dihydrochloride 1%, thimerosal 0.5%, and methyldibromo-glutaronitrile 0.1% from the European baseline series of allergens; information was also collected for ICDRG evaluation, an extended MOAHLFA index and patient-reported outcomes (daily routine questionnaire). The chi-square test for independence and Spearman’s rank were used to evaluate the association and correlation, respectively, between patient characteristics and ACD-related factors. Multiple correspondence analysis (MCA), which is a data analysis approach, was used to find and depict underlying structures in the data collection for nominal categorical data. Statistically significant associations were found between the following pairs of characteristics: eczema triggers and gender and eczema triggers and hand dermatitis. The results from MCA showed that there is correlation between allergic contact dermatitis onset, allergens, and demographic variables.

PMID:37486488 | DOI:10.1007/978-3-031-31982-2_15

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Cognitive Neurorehabilitation in Epilepsy Patients via Virtual Reality Environments: Systematic Review

Adv Exp Med Biol. 2023;1424:135-144. doi: 10.1007/978-3-031-31982-2_14.

ABSTRACT

OBJECTIVE: Epilepsy patients could possibly benefit from the remuneration observed in the use of virtual reality (VR) and virtual environments (VEs), especially in cognitive difficulties associated with visuospatial navigation (memory, attention, and processing speed).

AIM: Research questions under consideration in the present systematic review are associated to VEs’ efficiency as a cognitive rehabilitation practice in epilepsy and the particular VR methods indicated for epilepsy patients. To meet criteria, studies included participants suffering from any form of epilepsy and a methodological design with a structured rehabilitation program/model. Data were collected online, using academic databases.

RESULTS: Fourteen studies were included in the literature review and 6 in the statistical analysis. ROBINS-I protocol was implemented to assess the risk of bias. An inverse variance analysis (random effects) of pooled estimates of differences was implemented, in the form of continuous data. Despite the heterogeneity of the studies, all of them agree on the beneficial aspects of VR and VEs in cognitive rehabilitation in relation to visuospatial memory, attention, and information processing speed.

CONCLUSION: We suggest that patients suffering from epilepsy may benefit from the use of VR cognitive rehabilitation interventions, concerning visuospatial memory, attention, and information processing speed. However, further investigation is needed in order to gain a better understanding of the mechanisms involved in cognitive rehabilitation via VEs and establish efficient and dynamic rehabilitation protocols.

PMID:37486487 | DOI:10.1007/978-3-031-31982-2_14

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Detection of high-risk patients resistant to CDK4/6 inhibitors with hormone receptor-positive HER2-negative advanced and metastatic breast cancer in Japan (KBCSG-TR-1316)

Breast Cancer. 2023 Jul 24. doi: 10.1007/s12282-023-01485-y. Online ahead of print.

ABSTRACT

BACKGROUND: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) improve the prognosis of hormone receptor-positive HER2-negative advanced/metastatic breast cancer (HR+/HER2- mBC). However, some cancers show resistance to CDK4/6i and have a poor prognosis. The non-luminal disease score (NOLUS) was developed to predict non-luminal disease using immunohistochemical analysis.

METHODS: The association between the efficacy of CDK4/6i and NOLUS was investigated by evaluating pathological and clinical data, including real-world progression-free survival (rw-PFS) and overall survival (OS). Real-world data of patients with HR+/HER2- mBC who received CDK4/6i therapy [palbociclib or abemaciclib] as first- or second-line endocrine treatments was obtained. NOLUS was calculated using the formula: NOLUS (0-100) = – 0.45 × estrogen receptor (ER) (%) – 0.28 × progesterone receptor (PR) (%) + 0.27 × Ki67(%) + 73, and the patients were divided into two groups: NOLUS-positive (≥ 51.38) and NOLUS-negative (< 51.38).

RESULTS: Of the 300 patients, 28 (9.3%) were NOLUS-positive, and 272 (90.7%) were NOLUS-negative. The expression rates (%) of ER and PgR in NOLUS-positive patients were lower than those in NOLUS-negative patients (p < 0.001). Ki67 expression was higher in NOLUS-positive patients. There were statistically significant differences in prognosis (rw-PFS and OS) between the two groups. Moreover, NOLUS-negative patients showed statistically better rw-PFS with first-line therapy than second-line therapy. However, NOLUS-positive patients showed poor prognoses with both the first and second therapeutic lines, suggesting CDK4/6i inefficacy for NOLUS-positive patients.

CONCLUSIONS: The efficacy and prognosis of CDK4/6i significantly differed between the NOLUS-positive and NOLUS-negative patients. This feasible method can predict patients with HR+/HER2- mBC resistant to CDK4/6i and help select a better therapeutic approach to overcome resistance.

PMID:37486454 | DOI:10.1007/s12282-023-01485-y