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In Silico Design and Experimental Validation of Novel Oxazole Derivatives Against Varicella zoster virus.

Varicella zoster virus (VZV) infection causes severe disease such as chickenpox, shingles, and postherpetic neuralgia, often leading to disability. Reactivation of latent VZV is associated with a decrease in specific cellular immunity in the elderly and in patients with immunodeficiency. However, due to the limited efficacy of existing therapy and the emergence of antiviral resistance, it has become necessary to develop new and effective antiviral drugs for the treatment of diseases caused by VZV, particularly in the setting of opportunistic infections. The goal of this work is to identify potent oxazole derivatives as anti-VZV agents by machine learning, followed by their synthesis and experimental validation. Predictive QSAR models were developed using the Online Chemical Modeling Environment (OCHEM). Data on compounds exhibiting antiviral activity were collected from the ChEMBL and uploaded in the OCHEM database. The predictive ability of the models was tested by cross-validation, giving coefficient of determination q = 0.87-0.9. The validation of the models using an external test set proves that the models can be used to predict the antiviral activity of newly designed and known compounds with reasonable accuracy within the applicability domain (q = 0.83-0.84). The models were applied to screen a virtual chemical library with expected activity of compounds against VZV. The 7 most promising oxazole derivatives were identified, synthesized, and tested. Two of them showed activity against the VZV Ellen strain upon primary in vitro antiviral screening. The synthesized compounds may represent an interesting starting point for further development of the oxazole derivatives against VZV. The developed models are available online at OCHEM http://ochem.eu/article/145978 and can be used to virtually screen for potential compounds with anti-VZV activity.

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A Permanent Articulating Spacer versus Two-Stage Exchange for Chronic PJI: A Propensity-Score Matched Study.

Although two-stage revision has been proposed as gold standard for periprosthetic joint infection (PJI) treatment, limited evidence exists for the role of articulating spacers as definitive management. The purpose of this study was to compare clinical outcomes and costs associated with articulating spacers (1.5-stage) and a matched 2-stage cohort.

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Incidence and Risk Factors of Iliopsoas Tendinopathy after Total Hip Arthroplasty: A Radiographic Analysis of 1,602 Hips.

Iliopsoas tendinopathy (IPT) can cause persistent groin pain and lead to dissatisfaction after total hip arthroplasty (THA). This study aimed to report the characteristics, incidences, risk factors, and treatment outcomes of IPT after THA.

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Association of persistent morbidity after radiotherapy with quality of life in locally advanced cervical cancer survivors.

To quantify the association of persistent morbidity with different aspects of quality of life (QOL) in locally advanced cervical cancer (LACC) survivors.

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Implementation of CYP2D6-guided opioid therapy at Cincinnati Children’s Hospital Medical Center.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

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Pre-hospital analgesia in pediatric trauma and critically ill patients: An analysis of a German air rescue service.

Pain management in the pre-hospital setting remains a particular challenge for paramedics and emergency physicians, especially in children. This study evaluates the pre-hospital use and effect of analgesics in children with trauma or pain due to other reasons.

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Superior capsular reconstruction using hybrid graft for irreparable massive rotator cuff tear.

To evaluate the clinical and radiological outcomes of arthroscopic superior capsular reconstruction (SCR) using hybrid grafts composed of tensor fascia lata autografts and human dermal allografts.

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Safety, tolerability, and immunogenicity of the chimpanzee adenovirus type 3-vectored Marburg virus (cAd3-Marburg) vaccine in healthy adults in the USA: a first-in-human, phase 1, open-label, dose-escalation trial.

WHO has identified Marburg virus as an emerging virus requiring urgent vaccine research and development, particularly due to its recent emergence in Ghana. We report results from a first-in-human clinical trial evaluating a replication-deficient recombinant chimpanzee adenovirus type 3 (cAd3)-vectored vaccine encoding a wild-type Marburg virus Angola glycoprotein (cAd3-Marburg) in healthy adults.

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Factors contributing to a longer length of stay in adults admitted to a quaternary spinal care center.

Longer hospital length of stay (LOS) has been associated with worse outcomes and increased resource utilization. However, diagnostic and patient-level factors associated with LOS have not been well studied on a large scale. The goal was to identify patient, surgical and organizational factors associated with longer patient LOS for adult patients at a high-volume quaternary spinal care center.

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The effects of immersion in 42℃ radon, natrium, calcium, bicarbonate content thermal-mineral water on chronic low back pain. Controlled, follow-up study.

In our minimized follow-up trial with 137 participants with chronic low back pain, one group of participants received regular outpatient care, and the other group received balneotherapy by immersion in 42℃ thermal-mineral water in addition to regular outpatient care on 15 occasions for 3 weeks. Pain on movement and at rest on the 0-100 mm visual analogue scale (VAS), Oswestry index, the number of participants evaluating the symptoms clinically acceptable (Patient Acceptable Symptom State, PASS) and the EuroQol-5D-5L (EQ-5D-5L) quality of life questionnaire were assessed at basal time (at week 0) and after balneotherapy (at weeks 3 and 12). The VAS pain scores, the Oswestry index, the EQ-5D-5L index and the EQ-VAS significantly improved in the balneotherapy group after treatment at week 3 (p < 0.001) and week 12 (p < 0.001) compared to baseline, with a significant between group difference at week 3 (p < 0.001) and week 12 (p < 0.001). The pain VAS score on movement was 66.82 ± 11.48, 26.69 ± 21.49, and 20.09 ± 23.29 in the balneotherapy group, and 63.67 ± 14.77, 67.35 ± 15.44, and 70.23 ± 18.26 in the control group at the consecutive visits. The PASS increased in both groups at week 3 and week 12 compared to the baseline, with a significant between-group difference at week 3 and week 12 for the balneotherapy group. Our results suggest the therapeutic efficacy of immersion in 42℃ thermal mineral water on chronic low back pain.ClinicalTrials.gov Identifier: NCT05342051.

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