Miracle-dz/UniFAR-FTUs huggingface dataset:
Polymer-based thermoresponsive hydrogels for controlled drug delivery

ABSTRACT Introduction Controlled drug delivery through hydrogels is generally limited by the poor barrier that polymeric network can create to diffusion mechanism. Stimuli responsive polymers can help in this way guaranteeing that delivery can be sustained and finely controlled using an external stimulus. Area covered This review provides an overview of recent studies about the use of temperature as an external stimulus able to work as an efficient new route of drug’s administration. Thermoresponsive hydrogels are discussed and compared in terms of physical properties and mechanism of drug release considering their classification in intrinsical (formed by thermosensitive polymers) and non-intrinsical (polymers with thermosensitive moieties) hydrogels. Expert opinion Thermoresponsive hydrogels can be developed by using different polymers added or not with micro/nanoparticles of organic or inorganic origin. In both cases, the final system represents an innovative way for the local and sustained drug delivery in a specific site of the body. In particular, it is possible to obtain an on-demand release of drug by applying a local increase of temperature to the system.
Myelin water fraction mapping from multiple echo spin echoes and an independent B1 + map

Myelin water fraction (MWF) is often obtained from a multiple echo spin echo (MESE) sequence using multi‐component T2 fitting with non‐negative least squares. This process fits many unknowns including B1+ to produce a T2 spectrum for each voxel. Presented is an alternative using a rapid B1+ mapping sequence to supply B1+ for the MWF fitting procedure.
Physical problems of prolonged use of personal protective equipment during the COVID‐19 pandemic: A scoping review

Abstract Background It is widely believed that using personal protective equipment (PPE) provides high levels of protection for healthcare workers (HCWs) in the fight against coronavirus disease (COVID‐19). However, the long‐term use of PPE is inconvenient for HCWs and may cause physical discomfort. These factors could result in poor compliance and disrupt the health and safety of HCWs, which may negatively affect the patient's safety. Objective This study aimed to investigate the literature for the purpose of collecting convincing evidence of HCWs' physical problems associated with PPE use during the COVID‐19 pandemic. Methods This scoping review was conducted using PubMed, Embase, ProQuest, Science Direct, Springer, Biomed Central, and Google Scholar to identify the related literature. Results HCWs have experienced various physical disorders including skin, respiratory, musculoskeletal, nervous, urinary, and circulatory system problems that are associated with PPE in various body systems. Among these, skin problems were the most frequent physical problems. Conclusions The literature demonstrated the adverse impacts of using PPE on HCWs. Therefore, healthcare policymakers should take the appropriate measures to improve the work environment during the COVID‐19 pandemic, which could consequently prevent and mitigate the adverse effects of using PPE.
Beta-Blocker Therapy in Patients With Severe Traumatic Brain Injury: A Systematic Review and Meta-Analysis

Introduction Traumatic brain injury (TBI), a leading cause of morbidity and mortality among trauma patients worldwide, poses the risk of secondary neurological insult due to significant catecholamine surge. We aim to investigate the effectiveness and outcomes of beta-blocker administration in patients with severe TBI. Methods A search through PubMed, EMBASE, JAMA network, and Google Scholar databases was conducted for relevant peer-reviewed original studies published before February 15, 2022. A standard random-effects model was used, as justified by a high Cohen’s Q test. Results Twelve studies met inclusion criteria and were included in the meta-analysis. Severe TBI patients who were administered beta-blockers had a significantly reduced incidence of in-hospital mortality compared to the non-beta-blocker group (14.5% vs 19.2%). However, the beta-blocker group was reported to have a significantly greater number of ventilator days (5.58 vs 2.60 days). Similarly, intensive care unit (9.00 vs 6.84 days) and hospital (17.30 vs 11.02 days) lengths of stay (LOS) were increased in the beta-blocker group compared to those who were not administered beta-blocker therapy, but only the difference in hospital-LOS was significant. Conclusions Beta-blockers have significantly decreased in-hospital mortality in patients with severe TBI despite being associated with an increase in ventilator days and hospital-LOS. The administration of beta-blocker therapy in the management of severe TBI may be warranted and should be discussed in future guidelines.
COVID-19 Vaccinations and Anxiety in Middle-Aged and Older Jews and Arabs in Israel: The Moderating Roles of Ethnicity and Subjective Age

Subjective age (i.e., feeling younger/older than one’s chronological age) plays a significant role in older minority group members’ psychological well-being. In light of the importance of vaccinations for fighting COVID-19, it is unclear whether ethnicity and subjective age moderate the connection between receiving COVID-19 vaccinations and anxiety in Israel. Jewish (n = 198) and Arab older adults (n = 84) provided information regarding COVID-19 vaccinations, subjective age, and anxiety symptoms, as well as additional socio-demographic and COVID-19-related health factors (age range= 40–100, M = 62.5, SD = 12.34). Results demonstrated that feeling older was associated with increased anxiety (p < .001) and that vaccinations were linked to increased anxiety among Jews (p < .05). Moreover, the association between COVID-19 vaccinations and anxiety was significant only among Jewish participants with an older subjective age (p < .05). We stress the importance of examining cultural diversities regarding the contribution of subjective age in the context of COVID-19 and psychological well-being.
Orthographic facilitation of oral vocabulary acquisition in primary school children

Children’s oral vocabulary acquisition is an important aspect of language development that plays a crucial role in reading and literacy development and subsequent academic success. Therefore, it is important to identify and implement evidence-based effective strategies of vocabulary instruction for primary school children. Orthographic facilitation refers to the benefit afforded to word learning by incidentally presenting spellings when new words are introduced. This study aimed to replicate the orthographic facilitation effect in primary school (Grades 1–6) children and further assess whether children in different grades benefitted differently from the presence of orthography during spoken word learning. To do this, 91 children from Grades 1 to 6 were taught novel picture–word pairs with or without spellings. Word learning was assessed during and after training using behavioural and eye-tracking data from picture-naming and picture–word-matching (PWM) tasks. Irrespective of grade, all children experienced a significant orthographic facilitation effect during training. The post-training results were more task dependent with all grades showing a significant orthographic facilitation effect on the picture-naming task, and only Grades 1 to 4 showing a facilitation effect on the PWM task. The theoretical and practical implications of these findings are discussed.
Upregulation of mitochondrial ATPase inhibitory factor 1 (ATPIF1) mediates increased glycolysis in mouse hearts

In hypertrophied and failing hearts, fuel metabolism is reprogrammed to increase glucose metabolism, especially glycolysis. This metabolic shift favors biosynthetic function at the expense of ATP production. Mechanisms responsible for the switch are poorly understood. We found that inhibitory factor 1 of the mitochondrial FoF1-ATP synthase (ATPIF1), a protein known to inhibit ATP hydrolysis by the reverse function of ATP synthase during ischemia, was significantly upregulated in pathological cardiac hypertrophy induced by pressure overload, myocardial infarction, or α-adrenergic stimulation. Chemical cross-linking mass spectrometry analysis of hearts hypertrophied by pressure overload suggested that increased expression of ATPIF1 promoted the formation of FoF1-ATP synthase nonproductive tetramer. Using ATPIF1 gain- and loss-of-function cell models, we demonstrated that stalled electron flow due to impaired ATP synthase activity triggered mitochondrial ROS generation, which stabilized HIF1α, leading to transcriptional activation of glycolysis. Cardiac-specific deletion of ATPIF1 in mice prevented the metabolic switch and protected against the pathological remodeling during chronic stress. These results uncover a function of ATPIF1 in nonischemic hearts, which gives FoF1-ATP synthase a critical role in metabolic rewiring during the pathological remodeling of the heart.
Liquid biopsy assay for pulmonary adenocarcinoma using supernatants from core‐needle biopsy specimens

Genomic testing is the cornerstone of the treatment of patients with non‐small‐cell lung cancer. However, comprehensive molecular testing of small specimens may be inadequate due to limited tissue. Liquid biopsy has emerged as a new method of genotyping. In this study, we evaluate the feasibility of using supernatants from core needle biopsy samples of lung adenocarcinoma for genomic testing.
Recent progress in the structural study of ion channels as insecticide targets

Ion channels, many expressed in insect neural and muscular systems, have drawn huge attention as primary targets of insecticides. With the recent technical breakthroughs in structural biology, especially in cryo‐electron microscopy (cryo‐EM), many new high‐resolution structures of ion channel targets, apo or in complex with insecticides, have been solved, shedding light on the molecular mechanism of action of the insecticides and resistance mutations. These structures also provide accurate templates for structure‐based insecticide screening and rational design. This review summarizes the recent progress in the structural studies of 5 ion channel families: the ryanodine receptor (RyR), the nicotinic acetylcholine receptor (nAChR), the voltage‐gated sodium channel (VGSC), the transient receptor potential (TRP) channel, and the ligand‐gated chloride channel (LGCC). We address the selectivity of the channel‐targeting insecticides by examining the conservation of key coordinating residues revealed by the structures. The possible resistance mechanisms are proposed based on the locations of the identified resistance mutations on the 3D structures of the target channels and their impacts on the binding of insecticides. Finally, we discuss how to develop “green” insecticides with a novel mode of action based on these high‐resolution structures to overcome the resistance.
A first-in-human Phase I trial of the oral p-STAT3 inhibitor WP1066 in patients with recurrent malignant glioma

Aim: To ascertain the maximum tolerated dose (MTD)/maximum feasible dose (MFD) of WP1066 and p-STAT3 target engagement within recurrent glioblastoma (GBM) patients. Patients & methods: In a first-in-human open-label, single-center, single-arm 3 + 3 design Phase I clinical trial, eight patients were treated with WP1066 until disease progression or unacceptable toxicities. Results: In the absence of significant toxicity, the MFD was identified to be 8 mg/kg. The most common adverse event was grade 1 nausea and diarrhea in 50% of patients. No treatment-related deaths occurred; 6 of 8 patients died from disease progression and one was lost to follow-up. Of 8 patients with radiographic follow-up, all had progressive disease. The longest response duration exceeded 3.25 months. The median progression-free survival (PFS) time was 2.3 months (95% CI: 1.7 months-NA months), and 6-month PFS (PFS6) rate was 0%. The median overall survival (OS) rate was 25 months (95% CI: 22.5 months-NA months), with an estimated 1-year OS rate of 100%. Pharmacokinetic (PK) data demonstrated that at 8 mg/kg, the T1/2 was 2–3 h with a dose dependent increase in the Cmax. Immune monitoring of the peripheral blood demonstrated that there was p-STAT3 suppression starting at a dose of 1 mg/kg. Conclusion: Immune analyses indicated that WP1066 inhibited systemic immune p-STAT3. WP1066 had an MFD identified at 8 mg/kg which is the target allometric dose based on prior preclinical modeling in combination with radiation therapy and a Phase II study is being planned for newly diagnosed MGMT promoter unmethylated glioblastoma patients.
Black (patients’) lives matter: Exploring the role of identity-safety cues in healthcare settings among Black Americans

Two online experiments investigated whether hypothetical physicians’ use of an identity-safety cue acknowledging systemic injustice (a Black Lives Matter pin) improves Black Americans’ evaluations of the physician and feelings of identity-safety. Across studies, findings showed that when a White physician employed the identity-safety cue, Black Americans reported stronger perceptions of physician allyship and increased identity-safety (e.g. trust). As predicted, use of the identity-safety cue produced smaller or non-significant effects when employed by a Black physician. These benefits emerged regardless of physicians’ perceived motivation for employing the cue (e.g. whether the physician was personally motivated to employ the cue or his medical practice encouraged use of the cue; Study 2). Furthermore, analyses revealed that exposure to the identity-safety cue promoted a greater sense of identity-safety for Black Americans due to increased perceptions that the physician is an ally for Black individuals. Implications of identity-safety cues for racially discordant medical interactions are discussed.
Feasibility, Safety, and Short‐Term Outcomes of Transcatheter Patent Ductus Arteriosus Closure in Premature Infants on High‐Frequency Jet Ventilation

Background Prolonged exposure to a hemodynamically significant patent ductus arteriosus (PDA) is associated with major morbidity, particularly in infants born at <27 weeks’ gestation. High‐frequency jet ventilation (HFJV) is a standard of care at our center. There are no data about transcatheter PDA closure while on HFJV. The aim of this study was to assess the feasibility, safety, and outcomes of HFJV during transcatheter PDA closure. Methods and Results This is a retrospective cohort study of premature infants undergoing transcatheter device closure on HFJV. The primary outcome was successful device placement. Secondary outcomes included procedure time, fluoroscopy time and dose, time off unit, device complications, need for escalation in respiratory support, and 7‐day survival. Subgroup comparative evaluation of patients managed with HFJV versus a small cohort of patients managed with conventional mechanical ventilation was performed. Thirty‐eight patients were included in the study. Median age and median weight at PDA device closure for the HFJV cohort were 32 days (interquartile range, 25.25–42.0 days) and 1115 g (interquartile range, 885–1310 g), respectively. There was successful device placement in 100% of patients. There were no device complications noted. The time off unit and the procedure time were not significantly different between the HFJV group and the conventional ventilation group. Infants managed by HFJV had shorter median fluoroscopy times (4.5 versus 6.1 minutes; P<0.05) and no increased risk of adverse respiratory outcomes. Conclusions Transcatheter PDA closure in premature infants on HFJV is a safe and effective approach that does not compromise device placement success rate and does not lead to secondary complications.
iBCS: 1. Principles and Framework of an Inhalation-Based Biopharmaceutics Classification System

For oral drugs, the formulator and discovery chemist have a tool available to them that can be used to navigate the risks associated with the selection and development of immediate release oral drugs and drug products. This tool is the biopharmaceutics classification system (giBCS). Unfortunately, no such classification system exists for inhaled drugs. The perspective outlined in this manuscript provides the foundational principles and framework for a classification system for inhaled drugs. The proposed classification system, an inhalation-based biopharmaceutics classification system (iBCS), is based on fundamental biopharmaceutics principles adapted to an inhalation route of administration framework. It is envisioned that a classification system for orally inhaled drugs will facilitate an understanding of the technical challenges associated with the development of new chemical entities and their associated new drug products (device and drug formulation combinations). Similar to the giBCS, the iBCS will be based on key attributes describing the drug substance (solubility and permeability) and the drug product (dose and dissolution). This manuscript provides the foundational aspects of an iBCS, including the proposed scientific principles and framework upon which such a system can be developed.
Palliative Care in the Trauma and Surgical Critical Care Settings: A Narrative Review

Background We aimed to conduct a narrative review of available literature to understand the use of palliative care in the trauma and surgical critical care setting. Methods PubMed, EMBASE, and Google Scholar databases were searched for studies investigating the use of palliative care in the trauma and surgical critical care setting. The search included all studies published through January 9th, 2022. The risk of bias of included studies was assessed using the Joanna Briggs Institute Critical Appraisal Checklist tools. Outcomes were summarized in tables and synthesized qualitatively. Results A total of 22 studies were included in this review. Key elements of successful palliative care include communication, shared decision-making, family involvement, pain control, establishing a patient’s prognosis, and end-of-life management. Approaches to implementation based upon these key elements include best-case/worst-case scenarios, consultation trigger systems, and integrated institutional palliative care programs. Palliative care may reduce hospital length of stay, improve symptom management, and increase patient satisfaction, but the impact on mortality is unclear. Conclusion The core elements of palliative care have been identified and palliative care has been shown to improve outcomes in trauma and surgical critical care. However, the approaches for implementation still require development. The underutilization of palliative care for trauma patients reveals the need for refining criteria for use of palliative care and improvement in the education of surgical critical care teams to provide primary palliative care services.
It practically drives itself: autonomous vehicle technology, psychological attitudes, and susceptibility to risky driving behaviors

Abstract This study examines how favourable attitudes towards autonomous vehicle technology and automation-induced complacency relate to unsafe driving behaviours using semi-autonomous vehicles as an exemplar. The sample consisted of 441 college students and a repeated measures design was used to examine the relationships between psychological attitudes and susceptibility to risky driving behaviours across three scenarios. Linear regression analyses were conducted for hypothesis testing. Study 1 showed that favourable attitudes towards autonomous vehicle technologies were not significantly associated with susceptibility to risky driving behaviours. Study 2 replicated this finding, however, automation-induced complacency was significantly associated with susceptibility to risky driving behaviours. Additionally, evidence was found for the incremental validity of automation-induced complacency over favourable attitudes towards autonomous features. In distinguishing favourable attitudes towards autonomous features from automation-induced complacency, future research and policy-making can separately address these constructs for the promotion of traffic safety and policy-making. Practitioner summary: We aimed to assess inclinations towards risky driving behaviours in semi-autonomous vehicles. Using vignettes, we found that favourable attitudes towards autonomous vehicles are not associated with risky behaviours, but automation-induced complacency was. Our findings suggest policies like educational programs can be implemented to prevent misuse of semi-autonomous vehicles.
An Attentive Blank Stare Under Simulator-induced Spatial Disorientation Events

Objective This study investigated the effect of the spatial disorientation (SD) events on an attentive blank stare in the cockpit scene and demonstrated how much the flight task and visual delayed discrimination task were competing for the pilots’ attention. Background SD in flight is the leading cause of human error-related aircraft accidents in the military, general and commercial aviation, and has been an unsolved problem since the inception of flight. In-flight safety research, visually scanning cockpit instruments, and detecting changes are critical countermeasures against SD. Method Thirty male military pilots were performing a dual task involving piloting a flight simulator and visual change detection, while eye movements were obtained using an eye tracker. Results Pilots made more flight errors and spent less time gazing at the area of change in SD-conflict than in non-conflict flights. The vestibular origin SD-conflict led not only to deteriorated piloting and visual scanning but also to problems coordinating overt and covert attention, resulting in lower noticeability of visual changes despite gazing at them. Conclusion Our study shows that looking at a given area in space is not a sufficient condition for effective covert attention allocation and the correct response to a visual stimulus. It seems to be important to make pilots aware of this during SD training. Application To reduce change blindness, some strategies, such as reducing the number of secondary tasks is extremely valuable. Particular efforts should also be focused on improving the design of the aircraft cockpit by increasing the conspicuousness of critical information.