Molecular Simulations of Hydrogen Sorption in Semicrystalline High-Density Polyethylene: The Impact of the Surface Fraction of Tie-Chains

The modeling of the barrier properties of semicrystalline polymers has gained interest following the possible application of such materials as protective liners for the safe supply of pressurized hydrogen. The mass transport in such systems is intimately related to the complex intercalation between the crystal and amorphous phases, which was approached in this work through an all-atom representation of high-density polyethylene structures with a tailored fraction of amorphous–crystalline connections (tie-chains). Simulations of the polymer pressure–volume–temperature data and hydrogen sorption were performed by means of molecular dynamics and the Widom test particle insertion method. The discretization of the simulation domains of the semicrystalline structures allowed us to obtain profiles of density, degree of order, and gas solubility. The results indicated that the gas sorption in the crystalline regions is negligible and that the confinement of the amorphous phase between crystals induces a significant increase in density and a drop in the sorption capacity, even in the absence of tie-chains. Adding ties between the crystal and the amorphous phase results in further densification, an increase of the lamella tilt angle, and a decrease in the degree of crystallinity and hydrogen sorption coefficient, in agreement with several literature reference

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Feasibility of membrane processes for Volatile Fatty Acids (VFAs) concentration:data elaboration, modelling and design

The need for recovery and concentrate a Volatile Fatty Acids (VFAs) effluent resulting from a biological fermentation step, has aimed a feasibility study on pressure-driven membrane separation processing. A previous experimental campaign, carried out at LABIC-DICAM for the NoAW (No-Agricultural Waste) EU project, involving total recirculation and concentration trials on RO and NF modules, was the starting point for subsequent elaboration, modelling, simulation and preliminary design. The presented mass transfer-solution modelling allowed the estimation of both VFAs and Na+ real rejections for all investigated total recirculation trials. The modelling ability to assess the system’s osmotic pressure and polarization magnitude was successfully tested accounting for the validity of the osmotic-pressure model. Total recirculation trials calculated real rejections trends were interpolated using the Mason&Lonsdale and solution-diffusion transport models, providing a set of adjustable parameters. The interpolated RReal (Jv) curves were used in the simulation of the experimental concentration trials, proving our capability to fairly faithfully reproduce the experimental trends. The accomplishment encouraged the simulation of further concentration trials whose experimental evidence was not available. The simulations aimed at investigating the modules performances for different applied pressures with the final objective of identifying a few design best cases. Two possible process alternatives were proposed: pure RO process and an integrated process RO + NF. Subsequent comparison of the alternatives’ preliminary design best-cases showed the two to be competitive

Unusual Variant of Ameloblastoma with Calcifying Epithelial Odontogenic Tumor-like Areas in a Three-YearOld Child

The Calcifying Epithelial Odontogenic Tumor (CEOT) is a benign odontogenic tumor, comprising approximately 1% of all odontogenic tumors. It presents as a slow-growing tumor in posterior mandibular region. A three year-old female child from Multan, reported a swelling in right lower jaw progressively increasing in size eventually causing facial asymmetry. On intraoral examination, a protuberance was seen arising from posterior mandibular region and causing displacement of overlying teeth. The swelling was cystic on palpation and mildly tender. The patient underwent complete excision of lesion at a tertiary care center in her locality. The excision biopsy specimen was received at our lab which was intact and well preserved. A diagnosis of ameloblastoma with Calcifying epithelial odontogenic tumor-like areas was made. The patient was followed up after six months however no complaint of any recurrent swelling in the area of was recorded

Stem Cell Theory of Cancer: Implications for Translational Research from Bedside to Bench

A stem cell theory of cancer considers genetic makeup in the proper cellular context. It is a unified theory of cancer that unites the genome with the epigenome, links the intracellular with the extracellular, and connects the cellular constituents and compartments with the microenvironment. Although it allies with genomic medicine, it is better aligned with integrated medicine. In this perspective, we focus on translational research in cancer care. We expose some intrinsic fallacies in translational research when it relates to the basic principles of the scientific method in the care of patients with genomic medicine versus integrated medicine. We postulate that genomic medicine may be at the root of many failed efforts in drug development and data reproducibility. We propose an alternate heuristic approach that may expedite the development of safe and effective treatments and minimize the generation of unproductive pharmaceutical products and nonreproducible experimental results. Importantly, a heuristic approach emphasizes the role of a pertinent scientific theory and distinguishes therapy development from drug development, such that we discover not only useful drugs but also better ways to use them in order to optimize patient care and maximize clinical outcomes

A phase II multicenter study of enfortumab vedotin with or without pembrolizumab in rare genitourinary tumors (E-VIRTUE)

TPS4628 Background: Enfortumab vedotin (EV) is an antibody-drug conjugate (ADC) targeting nectin-4 with a monomethyl auristatin E (MMAE) payload, a potent microtubule inhibitor. It is standard of care (SOC) in metastatic urothelial carcinoma in combination with pembrolizumab in untreated patients and as monotherapy in post-chemotherapy, post-immune checkpoint blockade (ICB) patients. Nectin-4 expression has been retrospectively observed in 66.7-100% of urinary tract adenocarcinoma, 70-100% of urinary tract squamous cell carcinoma (SCC) (Case et al., 2022; Hoffman-Censits et al., 2021) and 36% of testicular germ cell tumors (GCTs) (The Human Protein Atlas). Metastatic urinary tract adenocarcinoma and SCC, and treatment refractory GCTs do not have an established SOC. Given the known nectin-4 expression, we hypothesize that EV with or without pembrolizumab will be active in these rare GU tumors. Methods: E-VIRTUE is an open-label, non-randomized, Phase 2 multicenter study. Eligible patients must have locally advanced or metastatic urinary tract pure adenocarcinoma, urinary tract pure SCC or refractory GCTs and have measurable disease by RECIST 1.1. Patients may have received any number of lines of prior systemic therapy except EV or other MMAE-based ADCs, and GCT patients must be refractory to all curative SOC treatments. Each histology will have an ICB-naïve and post anti-PD-1/PD-L1 ICB cohort: ICB-naïve patients will be given EV 1.25 mg/kg (maximum 125 mg) on Days 1 and 8 and pembrolizumab 200 mg on Day 1 of 21-day cycles, and post ICB patients will be given EV 1.25 mg/kg (maximum 125 mg) on Days 1, 8 and 15 of 28-day cycles. EV will be given for up to 5 years and pembrolizumab will be given for up to 2 years, or until progressive disease (PD) or unacceptable toxicity. Patients who stop pembrolizumab after achieving a complete response may resume it for 1 year after developing PD. The primary objective is to evaluate the objective response rate (ORR) in all cohorts. Secondary objectives include safety, progression-free survival (PFS) and overall survival (OS). The initial 6 cohorts will each be evaluated with exploratory intent. With 10 patients in each cohort, an exact binomial test with a 10% one-sided significance level will have 85.3% power to detect the difference between a very low (5%) ORR and a higher (30%) ORR. If there are ≥2/10 objective responses in any cohort, activity will be demonstrated. Additional histologies may be added after nectin-4 data emerges to justify their inclusion. Exploratory objectives include estimating the level of nectin-4 expression for each histology, performing DNA and RNA sequencing of tumor and blood samples, and observing changes in levels of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) with treatment and disease status. Clinical trial registration NCT06041503. Clinical trial information: NCT06041503