bluuebunny/crossref_metadata_2025 huggingface dataset:
Adjuvant activities of immunostimulating natural products: Astragalus membranaceus (Fisch.) Bge. and Coriolus versicolor in BNT162b2 vaccination against COVID-19 infection
Authors: Chan Ben Chung-Lap , Li Peiting , Tsang Miranda Sin-Man , Sung Johnny Chun-Chau , Kwong Keith Wai-Yeung , Zheng Tao , Hon Sharon Sze-Man , Lau Ching-Po , Ho Ronald Chi-Yan , Chen Fang , Lau Clara Bik-San , Leung Ping-Chung , Wong Chun-Kwok
Published: September 2023

The global pandemic of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been developing all over the world for more than 3 years. In late 2020, several variants of concern of SARS-CoV-2 virus emerged, with increased viral fitness and transmissibility by mutations of the spike proteins of the viral particle, denting hopes of the use of early-generation vaccines for a widespread protective immunity against viral infection. The use of adjuvants may enhance the immune responses of the conventional application of the COVID-19 vaccine. We have shown that the water extract of 2 β-glucan–enriched immunostimulating natural products, Astragalus membranaceus (Fisch.) Bge. (AM) and Coriolus versicolor (CV), could induce innate immunity-related cytokines from human monocytes (CCL5, interleukin [IL]-6, IL-10, and tumor necrosis factor α) and monocyte-derived dendritic cells (IL-1β, IL-10, IL-12, and tumor necrosis factor α). Using BALB/c mice, orally administrated AM and CV (1,384 and 742 mg/kg/d) for 4 d after vaccination, respectively, could enhance (1) the immunoglobulin G binding activities of BNT162b2 vaccination against ancestral and Delta SARS-CoV-2 spike proteins by 5.8- and 4.3-fold, respectively; (2) the immunoglobulin G3 subclass production of BNT162b2 vaccination against ancestral and variant SARS-CoV-2 spike proteins; and (3) the in vitro antibody-neutralizing activities of BNT162b2 vaccinated mice. In conclusion, combining AM and CV was effective in acting as an oral adjuvant with the messenger RNA vaccine BNT162b2 to improve the antigen binding activities against SARS-CoV-2 ancestral and variant SARS-CoV-2 spike proteins, probably via trained immunity of macrophages and dendritic cells.
A remarkably stable accretion disc in the Seyfert galaxy MCG-5-23-16
Authors: Serafinelli Roberto , Marinucci Andrea , De Rosa Alessandra , Bianchi Stefano , Middei Riccardo , Matt Giorgio , Reeves James N , Braito Valentina , Tombesi Francesco , Gianolli Vittoria E , Ingram Adam , Marin Frédéric , Petrucci Pierre-Olivier , Tagliacozzo Daniele , Ursini Francesco
Published: September 2023

MCG-5-23-16 is a Seyfert 1.9 galaxy at redshift z = 0.008 49. We analyse here the X-ray spectra obtained with X-ray Multi-Mirror (XMM)-Newton and Nuclear Spectroscopic Telescope Array (NuSTAR) data, which are the first contemporaneous observations with these two X-ray telescopes. Two reflection features, producing a narrow core and a broad component of the Fe Kα, are clearly detected in the data. The analysis of the broad iron line shows evidence of a truncated disc with inner radius $R_{\rm in}=40^{+23}_{-16}$Rg and an inclination of $41^{+9}_{-10}$°. The high quality of the NuSTAR observations allows us to measure a high-energy cut-off at $E_{\rm cut}=131^{+10}_{-9}$ keV. We also analyse the reflection grating spectrometer spectrum, finding that the soft X-ray emission is produced by two photoionized plasma emission regions, with different ionization parameters and similar column densities. Remarkably, the source only shows moderate continuum flux variability, keeping the spectral shape roughly constant in a time-scale of ∼20 yr.
Statistical X-ray analysis of gamma-ray-emitting radio galaxies
Authors: Matake Hiroto , Fukazawa Yasushi
Published: September 2023

We systematically analyzed Swift/XRT X-ray data of gamma-ray-emitting radio galaxies (RGs) to study the origin of X-ray radiation. We studied the short-duration variability of spectra by using Swift/XRT data for 20 RGs. We found that gamma-ray-emitting RGs with a higher gamma-ray-to-X-ray flux ratio show a strong harder-when-brighter behavior. In addition, gamma-ray-emitting RGs with soft gamma-ray spectral index tend to have a hard X-ray spectral index and vice versa. Based on these properties, we imply a trend that gamma-ray-emitting RGs could be roughly classified into three types of X-ray emission: jet-dominated type, disk/corona-dominated type, and intermediate type. This classification is quite consistent with the optical and radio classification of RGs. In addition, we also discuss this result in terms of the Eddington luminosity ratio. These interpretations should be confirmed using larger samples of RGs in the future.
Rapid analysis of 226Ra in ultrapure gadolinium sulfate octahydrate
Authors: Sakakieda Y , Hosokawa K , Nakanishi F , Hino Y , Inome Y , Sakaguchi A , Takaku Y , Yamasaki S , Sueki K , Ikeda M , Sekiya H
Published: September 2023

Numerous particle physics experiments utilize gadolinium (Gd), a rare earth element with the most significant neutron capture cross-section among all elements, to detect anti-neutrinos via inverse beta decays or to remove neutron-induced background events. For example, to load Gd into water Cherenkov detectors, Gd2(SO4)3 · 8H2O is dissolved and rare event search experiments are required to screen for radioactive impurities in Gd2(SO4)3 · 8H2O before dissolution. This study developed a new method to rapidly measure the radium-226 (226Ra) concentration in Gd2(SO4)3 · 8H2O. This method requires only 3 days to measure a batch of samples, as opposed to the usual method using high-purity germanium detectors, which takes approximately 20 days after arrival. The detection limit for the measurement of 226Ra concentration in Gd2(SO4)3 · 8H2O is 0.43 mBq/kg. This method has been already used for Gd2(SO4)3 · 8H2O screening at the Super-Kamiokande Gd (SK-Gd) project, and it can be applied to future experiments.
A silicon photomultiplier based compact gamma spectrometer for environmental gamma radiation monitoring networks
Authors: Srivastava Saurabh , Mitra Pratip , Kumar Amit , Tyagi Mohit , Kumar Aerattukkara Vinod , Topkar Anita
Published: September 2023

In this paper, the details of the development and performance characterisation of a compact, low-power gamma spectrometer for environmental gamma radiation monitoring networks are presented. To reduce the power consumption and the size of the spectrometer, a gamma detector comprising a silicon photomultiplier coupled to a Gd3Ga3Al2O12:Ce,B (GGAG:Ce,B) scintillator has been used for gamma spectrometry. Initially, a Monte Carlo simulation study was carried out to verify the suitability of the 5 mm × 5 mm × 5 mm GGAG:Ce,B crystal for spectrometry of gamma sources in the energy range 60–1332 keV. For minimising the power consumption, the signal processing electronics has been custom designed. This electronics was realised using standard off-the-shelf components to reduce the cost. The developed spectrometer is of size 16 cm × 10 cm × 6 cm, weighs 600 g and consumes 600 mW power. The spectrometer is developed such that it could be directly interfaced with GSM/Xbee for wireless communication with the radiation monitoring networks. The lower-level discriminator threshold of the system is 40 keV and the total electronic noise is <20 keV. The experimentally measured sensitivity of the spectrometer for 137Cs (662 keV) is 2.4 cps/μGy/h at 3.5 V overvoltage. The spectrometer offers excellent linearity over the measured energy range of 60–1332 keV and an energy resolution of ~10% for 662 keV gamma-ray at room temperature.
Attitudes Towards Standardization of Mesenchymal Stromal Cells—A Qualitative Exploration of Expert Views
Authors: Wilson Alison J , Brown Nik , Rand Emma , Genever Paul G
Published: September 2023

Pharmacopoeial standards ensure quality control of established medicines. It is widely believed that translation of cell therapy medicines will be facilitated by defining and adopting relevant standards. Mesenchymal stromal cells (MSCs) are used extensively for multiple indications in regenerative medicine. They are highly heterogeneous in terms of their biological characteristics and their mechanisms of action, making standardization a challenging undertaking. Furthermore, the use of MSCs in therapy appears to attract diverse views, ranging from concern and caution to enthusiastic positivity. We conducted semi-structured interviews with 20 expert stakeholders from academia, industry, regulatory agencies, non-governmental organizations and clinicians to explore their views, experiences, recommendations, and concerns regarding standardization of MSCs. Qualitative thematic analysis of transcribed records led to development of a consensus framework, which identified 5 key themes to facilitate exploration of the interviews’ content.

On the basis of our findings, we conclude that (1) there is undoubtedly an appetite for standardization, particularly in development of assays that enable comparison or benchmarking across manufacturers, processes, and cell sources; (2) stakeholder groups are not homogeneous in their concerns and attitudes; (3) careful consideration must be given to the points along the development timeline at which different standardization approaches could be beneficial; and (4) the roles of standards could be promoted further for specific aspects of advanced therapy medicinal product (ATMP) development and regulation such as qualification of decentralized manufacturing sites. A unified cross-stakeholder approach will help to advance MSC therapeutics and other cell therapy medicines.
Anterior Quadratus Lumborum Block for Total Laparoscopic Hysterectomy
Authors: She Huiyu , Qin Yifan , Peng Wenrui , Zhou Yali , Dai Ying , Wang Yiting , Jiang Peng , Wu Jin
Published: September 2023

Objectives:

This study aimed to investigate the perioperative analgesic effects of anterior quadratus lumborum block (QLB) for total laparoscopic hysterectomy (TLH).

Methods:

One hundred patients undergoing TLH were randomized to receive an anterior QLB or placebo before general anesthesia. The primary and secondary outcomes were postoperative sufentanil consumption, intraoperative remifentanil demand, time to first opioid demand, numeric rating scale (NRS) pain scores, heart rate, mean arterial pressure, and complications within 24 h after surgery.

Results:

No significant intergroup differences were observed in sufentanil consumption within 24 hours after surgery. Remifentanil consumption during surgery was lower in the QLB group than that in the placebo group. At 1 h after surgery, the NRS scores of abdominal visceral pain at rest and during activity were 1.26 and 1.41 points lower than those in the placebo group. In other time points, the differences of abdominal visceral pain were neither statistically significant nor clinically significant (pain difference <1) or both. No significant differences in NRS scores of shoulder pain, abdominal incisional pain and perineal pain were observed between the two groups, no matter at rest or during activity. There were no significant differences in other secondary outcome variables between the two groups.

Discussion:

Preoperative bilateral anterior QLB only reduced intraoperative opioid demand and postoperative abdominal visceral pain scores at 1 h after surgery. The clinical significance of anterior QLB in TLH may be limited.
Failure of Fixation in Trochanteric Hip Fractures: Does Nail Design Matter?
Authors: Davidson Amit , Giannoudis Peter V.
Published: September 2023

Objective:

The objective of this study was to compare clinical outcomes of patients with trochanteric hip fractures treated with specific different cephalomedullary nail (CMN) designs.

Methods:

A scoping review of the English literature was performed. Inclusion criteria were studies comparing perioperative and postoperative outcomes of trochanteric hip fractures fixated by CMNs for one of the following CMN designs: short versus long nails, blade versus screw fixation, dual versus single lag screw fixation, and application of cement augmentation. Inclusion criteria consisted of human comparative clinical trials (randomized and observational). Exclusion criteria included noncomparative studies, studies comparing CMN with non-CMN devices or with arthroplasty, studies with less than 3 months follow-up, studies that did not provide relevant clinical outcome measures, biomechanical, finite element analyses, animal, or in vitro publications. Data regarding reoperations, peri-implant fractures, mechanical failure, nonunion, infection rates, and functional outcomes were reviewed.

Results:

Twenty-two studies met the inclusion criteria and formed the basis of this study. Failure of fixation rates and reoperation rates for each of the nail designs selected for evaluation is presented, in addition to specific outcome measures relevant to that nail design which was explored: peri-implant fracture—short versus long nails, and specific mechanism of failure—blade versus plate.

Conclusions:

Decreased failure of fixation and reoperations rates were found for integrated dual lag screw fixation. Similar fixation failure and reoperation rates were found for the long versus short nails and for blade versus screw fixation.

Level of Evidence:

Diagnostic, Level IV.
Trust But Verify: Design Differences in The Prevention of Targeting Errors in Cephalomedullary Nails
Authors: Klima Matthew L.
Published: September 2023

Objectives:

To evaluate insertional damage on explanted cephalomedullary nails and to differentiate typical from atypical wear to characterize outliers.

Design:

Therapeutic.

Setting:

Level II trauma center.

Participants:

Patients who underwent removal of an implanted cephalomedullary nail for any reason from 2015 to 2023.

Methods:

Inspection of implants was performed at ×1000 magnification with a light microscope. Benchtop testing was performed with Gamma3, Gamma4, Intertan, TFN, and TFNa instrumentation.

Results:

One hundred nine cephalomedullary nails were inspected. Insertional damage was observed in more than 95% of the implants recovered. In 34% (37 of 109) of implants, damage to the proximal aperture was severe enough to cause a chamfer or “notch.” Chamfers were also encountered along the distal locking aperture in short stem implants in 44% (19 of 43). Guidewire chamfers to the proximal implant external to the aperture and damage to preinserted set screws were outliers. Evidence of set screw fracture or deformity was encountered in 12 specimens. Four anomalous set screw variants were encountered within 1 implant design, each variant exhibiting maltracking with deployment that could result in malfunction.

Conclusions:

Insertional damage to cephalomedullary implants was encountered routinely among the explants and should not always be categorized as preventable surgical error. Surgeons should be familiar with technical and design factors that contribute to chamfering of implants to reduce failures.

Level of Evidence:

Therapeutic, Level III
Defining Cephalomedullary Nail Breakage Rates: A Systematic Review and Meta-Analysis
Authors: Lambers Anton Philip , D'Alessandro Peter , Yates Piers
Published: September 2023

Objective:

To establish the background rate of breakage of cephalomedullary nails.

Data Sources:

MEDLINE, PubMed, and Web of Science were searched on April 3, 2023.

Study Selection:

All English-language studies that examined trochanteric with or without subtrochanteric fractures and identified cephalomedullary nail breakage as an outcome measure and a breakage rate could be derived were included. Implants captured were predominantly the TFNA, TFN, and PFN by DePuy Synthes, various versions of the Gamma nail by Stryker, the Zimmer Natural Nail by Zimmer Biomet, and the Intertan by Smith and Nephew.

Data Extraction:

The author, year of publication, dates of implant insertion, study design, method of detection of breakages, implant used, number of implant breakages, number of implants inserted, breakage rate, and follow-up were extracted.

Data Synthesis:

Meta-analysis of included studies used descriptive nonparametric statistics and a noncomparative proportion for the pooled result. Differences in results between study design types were compared using the mean breakage rate per study design.

Conclusions:

Cephalomedullary nail breakage is a rare complication with a median reported rate of 0.6% and a pooled result rate of 0.4%. Ninety-five percent of studies had a breakage rate of 1.3% or less, which sets a benchmark from the reported literature for future studies. There is wide variability in rates of breakage reported between different types of study designs with single-center review studies reporting breakage rates nearly 4-fold greater than large-scale administrative database reviews. The rate of implant breakage should not be used in isolation to judge an implant's performance.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Stability of Intertrochanteric Femur Fractures
Authors: Ricci William M.
Published: September 2023

The stability of intertrochanteric fractures depends upon multiple factors including the fracture displacement, location and pattern, the type of fixation used for stabilization, and the loading that the fracture undergoes postfixation. Traditional classification systems are of limited utility because they typically stratify intertrochanteric fractures as stable or unstable based purely on the fracture pattern without consideration of the stability after fixation. Biomechanical studies evaluating the stability of various fixation constructs should include physiologic loading, including rotation around the axis of the femoral neck, and reproduce clinical failure modes to be clinically relevant. A growing body of evidence indicates that the type of fixation substantially affects postoperative stability of intertrochanteric fractures.
Anorectic effect of COR659 in a rat model of overeating
Authors: Maccioni Paola , Mugnaini Claudia , Carai Mauro A.M. , Gessa Gian Luigi , Corelli Federico , Colombo Giancarlo
Published: September 2023

COR659 is a new compound, the action of which is exerted via a dual mechanism: positive allosteric modulation of the GABAB receptor; antagonism or inverse agonism at the cannabinoid CB1 receptor. Recent lines of experimental evidence have indicated that COR659 potently and effectively reduced operant self-administration of and reinstatement of seeking behaviour for a chocolate-flavoured beverage. The present study was designed to assess whether the ability of COR659 to diminish these addictive-like, food-motivated behaviours extended to a rat model of overeating palatable food. To this end, rats were habituated to feed on a standard rat chow for 3 h/day; every 4 days, the 3-hour chow-feeding session was followed by a 1-hour feeding session with highly palatable, calorie-rich Danish butter cookies. Even though satiated, rats overconsumed cookies. COR659 (0, 2.5, 5, and 10 mg/kg, i.p.) was administered before the start of the cookie-feeding session. Treatment with all 3 doses of COR659 produced a substantial decrease in intake of cookies and calories from cookies. These results extend the anorectic profile of COR659 to overconsumption of a highly palatable food and intake of large amounts of unnecessary calories.
Navigating the Ethical Landmines of ChatGPT: Implications of Intelligent Chatbots in Plastic Surgery Clinical Practice
Authors: Oleck Nicholas C. , Naga Hani I. , Nichols D. Spencer , Morris Miranda X. , Dhingra Bhuwan , Patel Ash
Published: September 2023

ChatGPT is a cutting-edge language model developed by OpenAI with the potential to impact all facets of plastic surgery from research to clinical practice. New applications for ChatGPT are emerging at a rapid pace in both the scientific literature and popular media. It is important for clinicians to understand the capabilities and limitations of these tools before patient-facing implementation. In this article, the authors explore some of the technical details behind ChatGPT: what it is, and what it is not. As with any emerging technology, attention should be given to the ethical and health equity implications of this technology on our plastic surgery patients. The authors explore these concerns within the framework of the foundational principles of biomedical ethics: patient autonomy, nonmaleficence, beneficence, and justice. ChatGPT and similar intelligent conversation agents have incredible promise in the field of plastic surgery but should be used cautiously and sparingly in their current form. To protect patients, it is imperative that societal guidelines for the safe use of this rapidly developing technology are developed.
Perspectives on pulsed field ablation: how to judge endpoints
Authors: Anglesio Valeria , Verma Atul
Published: September 2023

Purpose of review

This review highlights pulse field ablation's (PFA) significance in treating atrial fibrillation. PFA uses short-pulsed electrical fields, offering safety advantages over thermal methods. Multicenter studies’ findings on PFA's safety, efficiency, and efficacy, compared with thermal techniques, are discussed.

Recent findings

The review encompasses major PFA systems utilized in multicenter studies: penta-spline, circular, and lattice catheters. These studies affirm PFA's safety, with minimal complications like esophageal injury, phrenic nerve complications, and pulmonary vein stenosis. PFA also demonstrates procedural efficiency benefits because of rapid pulse delivery. However, PFA's efficacy appears on par with thermal ablation, showing similar rates of atrial arrhythmia recurrence during follow-up periods. The studies explore diverse postablation monitoring strategies, underscoring the necessity for standardized monitoring or consistent transformation of arrhythmia data.

In conclusion, PFA marks a promising era for atrial fibrillation treatment with improved safety and efficiency. Efficacy is comparable to thermal methods, though technology advancements could alter this. PFA's potential as a safer and faster alternative positions it as a dominant atrial fibrillation ablation technology. Careful analysis and standardized monitoring are vital to assess PFA's potential and clinical implications
Human Tear Protein Analysis Using a Quantitative Microfluidic System: A Pilot Study
Authors: Casemore Rachel K. , Wolffsohn James S. , Dutta Debarun
Published: September 2023

Objectives:

Human tears have the potential to be used as biomarkers to aid in the diagnosis and management of dry eye disease (DED). This prospective, controlled pilot study aimed to investigate the hypothesis that a panel of tear protein profiles can be detected and are repeatable when analyzed using a miniaturized quantitative microfluidic system.

Methods:

Ten participants were recruited following institutional ethics committee approval. Participants attended two visits 1 week apart when the following measurements were taken in a sequence: tear meniscus height, noninvasive breakup time, ocular redness, tear collection, and corneal and conjunctival staining. Basal tears (>4 µL) were collected using glass microcapillary tubes. Tears were processed to analyze a panel of proteins (14–230 kDa) following the manufacturer's guidelines using a miniaturized quantitative microfluidic system (Protein 230 LabChip with Agilent 2100 Bioanalyzer). Demographics of the clinical measurements and a comparison of the panel of identified proteins and their repeatability were made.

Results:

Mean age of the participants was 20.8±1.6 years, nine were females, three fulfilled the TFOS DEWS-II diagnostic criteria for DED. The total protein concentration across participants was 6.72±3.56 mg/mL. Several proteins (lysozyme C, lipocalin 1, IgA light chain, zinc-α2-glycoprotein, albumin, and lactoferrin) were identified at both visits for seven or more participants. There were no significant differences (P>0.05) in individual protein concentrations between the two visits. A high correlation was found between the two visits for all proteins where correlation coefficient ranged between 0.63 and 0.98 (P<0.05).

Conclusion:

The protein profiles measured by the quantitative microfluidic system are repeatable, thus validating quantitative microfluidic system as a reliable method for investigating a panel of tear proteins. This method is quick, affordable, requires only 4 μL of tear, and is relatively easy method to perform that can be incorporated in a clinical setting. Further studies in larger clinical setting may be beneficial exploring the usability of this method in various patient groups.
Optical Quality and Visual Performance With Different Toric Contact Lens Designs
Authors: Koh Shizuka , Maeda Naoyuki , Terao Misaki , Maeda Hiroko , Kosaki Ryo , Kozaki Jun , Nishida Kohji
Published: September 2023

Objectives:

To evaluate the optical quality of different toric contact lens (CL) designs and compare their on-eye visual correction performance.

Methods:

Twenty soft CL wearers aged 20 to 39 years were enrolled. Two daily disposable silicone-hydrogel toric CLs were tested: the “Eyelid Stabilized Design” (ESD-CL) and prism-ballast design (PB-CL); a spherical daily disposable silicone hydrogel CL (spherical CL) was used as a control. On-eye performance was compared for corrected distance visual acuity (CDVA), astigmatism, and ocular higher-order aberrations (HOAs); astigmatism and ocular HOAs were measured with a wavefront sensor. The subjective quality of vision, rated for “blurred vision” and “double vision,” lens rotation, and fitting were also compared.

Results:

The ESD-CLs, PB-CL, and no-CL provided better CDVA than spherical CL (P<0.05). Compared with spherical CL and no CL, PB-CL and ESD-CLs caused significantly lesser astigmatism (P<0.05). Coma was significantly lesser with ESD-CLs than that with PB-CL (P<0.05); total HOAs did not differ among the four conditions. The subjective ratings for blurred and double vision were significantly lower with ESD-CLs than those with spherical CL (P<0.05).

Conclusions:

Toric CLs provide a better CDVA than spherical CLs. However, differences in coma and subjective symptoms may occur because of the design of toric CLs.
Exploring the “Black Box” of Recommendation Generation in Local Health Care Incident Investigations: A Scoping Review
Authors: Lea William , Lawton Rebecca , Vincent Charles , O’Hara Jane
Published: September 2023

Background

Incident investigation remains a cornerstone of patient safety management and improvement, with recommendations meant to drive action and improvement. There is little empirical evidence about how—in real-world hospital settings—recommendations are generated or judged for effectiveness.

Objectives

Our research questions, concerning internal hospital investigations, were as follows: (1) What approaches to incident investigation are used before the generation of recommendations? (2) What are the processes for generating recommendations after a patient safety incident investigation? (3) What are the number and types of recommendations proposed? (4) What criteria are used, by hospitals or study authors, to assess the quality or strength of recommendations made?

Methods

Following PRISMA-ScR guidelines, we conducted a scoping review. Studies were included if they reported data from investigations undertaken and recommendations generated within hospitals. Review questions were answered with content analysis, and extracted recommendations were categorized and counted.

Results

Eleven studies met the inclusion criteria. Root cause analysis was the dominant investigation approach, but methods for recommendation generation were unclear. A total of 4579 recommendations were extracted, largely focusing on individuals’ behavior rather than addressing deficiencies in systems (<7% classified as strong). Included studies reported recommendation effectiveness as judged against predefined “action” hierarchies or by incident recurrence, which was not comprehensively reported.

Conclusions

Despite the ubiquity of incident investigation, there is a surprising lack of evidence concerning how recommendation generation is or should be undertaken. Little evidence is presented to show that investigations or recommendations result in improved care quality or safety. We contend that, although incident investigations remain foundational to patient safety, more enquiry is needed about how this important work is actually achieved and whether it can contribute to improving quality of care.
Comparison of Patient Education Materials Generated by Chat Generative Pre-Trained Transformer Versus Experts
Authors: Hung Ya-Ching , Chaker Sara C. , Sigel Matthew , Saad Mariam , Slater Elizabeth D.
Published: September 2023

Introduction

Improving patient education materials may improve patient outcomes. This study aims to explore the possibility of generating patient education materials with the assistance of a large language model, Chat Generative Pre-Trained Transformer (ChatGPT). In addition, we compare the accuracy and readability of ChatGPT-generated materials versus expert-generated materials.

Methods

Patient education materials in implant-based breast reconstruction were generated by experts and ChatGPT independently. Readability and accuracy of the materials are the main outcomes. Readability of the materials was compared using Flesch-Kincaid score. Accuracy of the materials generated by ChatGPT was evaluated by 2 independent reviewers. Content errors are categorized into information errors, statistical errors, and multiple errors (errors more than 2 types).

Results

The content generated by experts had higher readability. The Flesch-Kincaid score is at the 7.5 grade for expert-generated materials, whereas the content generated by ChatGPT is at the 10.5 grade (despite ChatGPT being asked to generate content at the seventh grade level). The accuracy of ChatGPT-generated content is 50%, with most errors being information errors. ChatGPT often provides information about breast reduction or breast augmentation, despite being asked specifically about breast reconstruction. Despite its limitation, ChatGPT significantly reduced the time required to generate patient education materials. Although it takes experts 1 month to generate patient education materials, ChatGPT generates materials within 30 minutes.

Conclusions

ChatGPT can be a powerful starting tool to generate patient education materials. However, its readability and accuracy still require improvements.
Diagnostic efficiency of the FilmArray blood culture identification (BCID) panel: a systematic review and meta-analysis
Authors: Yang Mei , Tao Chuanmin
Published: September 2023

Introduction. The FilmArray blood culture identification panel (BCID) panel is a multiplex PCR assay with high sensitivity and specificity to identify the most common pathogens in bloodstream infections (BSIs).

Hypothesis. We hypothesize that the BCID panel has good diagnostic performance for BSIs and can be popularized in clinical application.

Aim: To provide summarized evidence for the diagnostic accuracy of the BCID panel for the identification of positive blood cultures.

Methodology. We searched the MEDLINE, EMBASE and Cochrane databases through March 2021 and assessed the efficacy of the diagnostic test of the BCID panel. We performed a meta-analysis and calculated the summary sensitivity and specificity of the BCID panel. Systematic review protocols were registered in the International Prospective Register of Systematic Reviews (PROSPERO) (registration number CRD42021239176).

Results. A total of 16 full-text articles were eligible for analysis. The overall sensitivities of the BCID panel on Gram-positive bacteria, Gram-negative bacteria and fungi were 97 % (95 % CI, 0.96–0.98), 100 % (95 % CI, 0.98–01.00) and 99 % (95 % CI, 0.87–1.00), respectively. The pooled diagnostic specificities were 99 % (95 % CI, 0.97–1.00), 100 % (95 % CI, 1.00–1.00) and 100 % (95 % CI, 1.00–1.00) for Gram-positive bacteria, Gram-negative bacteria and fungi, respectively.

Conclusions. The BCID panel has high rule-in value for the early detection of BSI patients. The BCID panel can still provide valuable information for ruling out bacteremia or fungemia in populations with low pretest probability.
Propofol for treatment resistant depression: A randomized controlled trial
Authors: Tadler Scott C. , Jones Keith G. , Lybbert Carter , Huang Jason C. , Jawish Rana , Solzbacher Daniela , Kendrick E. Jeremy , Pierson Matthew D. , Weischedel Kamile , Rana Noreen , Jacobs Rebecca , Vonesh Lily C. , Feldman Daniel A. , Larson Claire , Hoffman Nathan , Jessop Jacob E. , Larson Adam L. , Taylor Norman E. , Odell David H. , Kuck Kai , Mickey Brian J.
Published: September 2023

Background

Anesthetic agents including ketamine and nitrous oxide have shown antidepressant properties when appropriately dosed. Our recent open-label trial of propofol, an intravenous anesthetic known to elicit transient positive mood effects, suggested that it may also produce robust and durable antidepressant effects when administered at a high dose that elicits an electroencephalographic (EEG) burst-suppression state. Here we report findings from a randomized controlled trial (NCT03684447) that compared two doses of propofol. We hypothesized greater improvement with a high dose that evoked burst suppression versus a low dose that did not.

Methods

Participants with moderate-to-severe, treatment-resistant depression were randomized to a series of 6 treatments at low versus high dose (n=12 per group). Propofol infusions were guided by real-time processed frontal EEG to achieve predetermined pharmacodynamic criteria. The primary and secondary depression outcome measures were the 24-item Hamilton Depression Rating Scale (HDRS-24) and the Patient Health Questionnaire (PHQ-9), respectively. Secondary scales measured suicidal ideation, anxiety, functional impairment, and quality of life.

Results

Treatments were well tolerated and blinding procedures were effective. The mean [95%-CI] change in HDRS-24 score was −5.3 [−10.3, −0.2] for the low-dose group and −9.3 [−12.9, −5.6] for the high-dose group (17% versus 33% reduction). The between-group effect size (standardized mean difference) was −0.56 [−1.39, 0.28]. The group difference was not statistically significant (p=0.24, linear model). The mean change in PHQ-9 score was −2.0 [−3.9, −0.1] for the low dose and −4.8 [−7.7, −2.0] for the high dose. The between-group effect size was −0.73 [−1.59, 0.14] (p=0.09). Secondary outcomes favored the high dose (effect sizes magnitudes 0.1 - 0.9) but did not generally reach statistical significance (p>0.05).

Conclusions

The medium-sized effects observed between doses in this small, controlled, clinical trial suggest that propofol may have dose-dependent antidepressant effects. The findings also provide guidance for subsequent trials. A larger sample size and additional treatments in series are likely to enhance the ability to detect dose-dependent effects. Future work is warranted to investigate potential antidepressant mechanisms and dose optimization.
Bayesian Maximum Entropy Ensemble Refinement
Authors: Eltzner Benjamin , Hofstadler Julian , Rudolf Daniel , Habeck Michael , de Groot Bert
Published: September 2023

The principle of maximum entropy provides a canonical way to include measurement results into a thermodynamic ensemble. Observable features of a thermodynamic system, which are measured as averages over an ensemble are included into the partition function by using Lagrange multipliers. Applying this principle to the system’s energy leads to the well-known exponential form of the Boltzmann probability density. Here, we present a Bayesian approach to the estimation of maximum entropy parameters from nuclear Overhauser effect measurements in order to achieve a refined ensemble in molecular dynamics simulations. To achieve this goal, we leverage advances in the treatment of doubly intractable Bayesian inference problems by adaptive Markov Chain Monte Carlo methods. We illustrate the properties and viability of our method for alanine dipeptide as a simple model system and trp-cage as an example for a more complex peptide.
An abundance of brain-expressed genes show ectopic activation in lung adenocarcinoma
Authors: Diacofotaki Anna , Loriot Axelle , De Smet Charles
Published: September 2023

Tumoral transformation processes sometimes include activation of unscheduled gene expression programs in the cancer cells. This is best exemplified by the so-called cancer-testis (CT) genes, a group of genes expressed in testicular germ cells that become activated in tumors of various somatic origins, through a process of DNA demethylation. Here, we explored the possibility that other tissue-specific gene clusters may become ectopically activated in tumors. Lung adenocarcinoma (LUAD) was used as a model, as all necessary transcriptomic datasets were available, including that ofAT2cells, the cell-of- origin of LUAD. We found that besides CT genes, an abundant group of genes expressed in the brain (CB genes, n=63) or in both brain and testis (CBT genes, n=28) become aberrantly activated in LUAD cell lines and tissues. Interestingly, activation of CB and CBTgene clusters was also detected in various other tumor types. Most CB/CBT genes appeared to exert neuronal functions. Moreover, a significant number of them encode antigens involved in neurological paraneoplastic syndromes. Neither neuroendocrine transdifferentiation, which occurs in 10-20% LUAD, nor DNA demethylation appeared to be responsible of the ectopic activation of CB and CBTgene clusters. Instead, prediction tools and depletion experiments identified the REST repressor as a regulator of a number of CB/CBT genes.Conclusion:Together, our data indicate that tumor development is associated with aberrant activation of a brain gene expression program, supporting the assumption that acquisition of neuronal functions might contribute to malignancy.
Local Mean and Pattern Standard Deviation Map for Disease Staging in Glaucoma
Authors: Mock Dennis C.
Published: September 2023

For monitoring disease progression in glaucoma, perimetric measurements as global indices such as the mean deviation and standard pattern deviation for the visual field perimetry do not maintain a consistent diagnostic sensitivity over the entire data range. Here an analytical approach that assumes an underlying Gaussian mixture model describing the normal visual field offers an alternative solution to this situation.
A role for LGI1 in regulating pain sensitivity
Authors: Farah Adham , Paul Ivan , Cheng Hoi , Su Yuhe , Poplawski Piotr , Tseng Mandy , Dawes John
Published: September 2023

Chronic pain represents a major unmet clinical need. Neuropathic pain, that is pain arising due to damage or disease of the somatosensory nervous system, represents a sizeable proportion of chronic pain cases, affecting around 8% of the general population. Neuronal hyperexcitability is a key driver of neuropathic pain. Leucine glioma inactivated 1 (LGI1), is a secreted protein known to regulate excitability within the nervous system and is the target of autoantibodies from neuropathic pain patients. Therapies that block or reduce antibody levels are highly effective at relieving pain in these patients, suggesting that LGI1 has an important role in clinical pain. Here we have studied the role of LGI1 in regulating pain using mouse models to specifically ablate LGI1 in neuron populations. LGI1 has been well studied at the level of the brain. Here we show that LGI1 is highly expressed in dorsal root ganglion (DRG) neurons and in dorsal horn neurons of the spinal cord. Using transgenic mice, we ablated LGI1, either specifically in nociceptors (LGI1fl/Nav1.8(+/-)), or in all DRG and spinal neurons (LGI1fl/Hoxb8(+/-)). On acute pain assays, mild phenotypes were observed when compared to littermate controls with limited changes in DRG neuron excitability. No differences were seen in the first phase of the formalin test, however LGI1fl/Hoxb8(+/-)mice displayed a significant increase in nocifensive behaviours in the second phase compared to littermate controls. Using the spared nerve injury model, we assessed the impact of LGI1 ablation on neuropathic pain-like behaviours. LGI1fl/Nav1.8(+/-)mice showed no differences in nerve injury induced mechanical hypersensitivity, brush-evoked allodynia or spontaneous pain behaviour compared to controls. However, LGI1fl/Hoxb8(+/-)mice showed a significant exacerbation of mechanical hypersensitivity and allodynia. These data show that LGI1 has a role in regulating pain sensitivity particularly in the context of nerve injury. We suggest this effect is likely mediated at the spinal level since no differences were observed following specific ablation of LGI1 in nociceptors. Neurons in dorsal horn of the spinal cord are important in gating nerve injury induced mechanical pain and our findings suggest that LGI1 plays an important role in this process.
Predicting genomic traits in ammonia-oxidizing archaea using phylogenetic signals
Authors: Redondo Miguel A. , Jones Christopher M. , Legendre Pierre , Guénard Guillaume , Hallin Sara
Published: September 2023

Phylogenetic conservatism of microbial traits has paved the way for phylogeny-based predictions, allowing us to move from descriptive to predictive functional microbial ecology. Here, we applied phylogenetic eigenvector mapping, an approach not previously used for microorganisms, to predict key traits of ammonia-oxidizing archaea (AOA), which are important players in nitrogen cycling. Using 168 nearly complete AOA genomes and metagenome assembled genomes from public databases, we predicted the distribution of 18 ecologically relevant genes across an updatedamoAgene phylogeny, including a novel variant of an ammonia transporter found in this study. Of the selected genes, 94% displayed a significant phylogenetic signal and gene presence was predicted with >88% accuracy, >88% sensitivity, and >80% specificity. The phylogenetic eigenvector approach performed equally well as ancestral state reconstruction of traits. We implemented the predictive models on anamoAsequencing dataset of AOA soil communities and show key ecological predictions, e.g., that AOA communities in nitrogen rich soils have capacity for ureolytic metabolism while those adapted to low pH soils have the high affinity ammonia transporter (amt2). Predicting genomic traits can shed light on the potential functions that microbes perform across earth biomes, further contributing to a better mechanistic understanding of their community assembly.
Inflammation and autophagy dysfunction in metachromatic leukodystrophy: a central role for mTOR?
Authors: Catchpole Zoe , Hartanto Annabelle , Kataura Tetsushi , Palmowski Pawel , Porter Andrew , Foster Emma , Ulicna Kristina , Pyle Angela , Taylor Robert , Harris Kate S. , Korolchuk Viktor , Erskine Daniel
Published: September 2023

Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder typically resulting from biallelic loss-of-function variants in theARSAgene which encodes the lysosomal enzyme, arylsulphatase A, leading to the accumulation of its substrate, sulphatide, and widespread demyelination. Although gene therapy is available for MLD, it is limited by high cost and a narrow window for intervention, which means the development of therapies for MLD remains a key goal. The aim of the present study was to explore disease mechanisms in MLD with a view to identifying novel targets for therapeutic intervention for patients who cannot avail of gene therapy.Postmortemglobus pallidus and dentate nucleus tissue was obtained from MLD cases (N=5; age 2-33 years old) and compared to age-, sex and ethnicity matched controls (N=5) and studied using discovery proteomics which demonstrated a marked inflammatory response, activation of the mTOR pathway, oxidative stress and metabolic remodelling in MLD cases. Histological analysis of inflammatory markers, including the terminal fragment of complement pathway activation, C3d, and the secreted glycoprotein YKL-40, a commonly used biomarker for inflammation, demonstrated their enrichment in MLD cases. Given that the mTOR pathway plays a key role in supressing autophagy, we next investigated autophagy and identified the accumulation of autophagosomes in MLD cases, consistent with deficient autophagy. Taken together, these findings suggest inflammation and autophagy dysfunction are key processes involved in MLD and that the mTOR pathway could be a novel therapeutic target for MLD.
Replay-triggered Brain-wide Activation in Humans
Authors: Huang Qi , Xiao Zhibing , Yu Qianqian , Luo Yuejia , Xu Jiahua , Dolan Ray , Behrens Tim , Liu Yunzhe
Published: September 2023

The consolidation of discrete experiences into a coherent narrative shape our cognitive map, providing a structured mental representation of our experiences. Neural replay, by fostering crucial hippocampal-cortical dialogue, is thought to be pivotal in this process. However, the brain-wide engagement coinciding with replay bursts remains largely unexplored. In this study, by employing simultaneous EEG-fMRI, we capture both the spatial and temporal dynamics of replay. We find that during mental simulation, the strength of on-task replay, as detected via EEG, correlates with heightened fMRI activity in the hippocampus and medial prefrontal cortex. Intriguingly, increased replay strength also enhances the functional connectivity between the hippocampus and the default mode network, a set of brain regions key to representing cognitive map. Furthermore, during the post-learning resting state, we observed a positive association between increased task-related reactivation, hippocampal activity, and augmented connectivity to the entorhinal cortex. Our findings elucidate the neural mechanism of human replay in both time and space, providing novel insights into dynamics of replay and associated brain-wide activation.
From differences to strengths: strategies for embracing generational diversity at workplace
Authors: Malik Shehla , Shahid Shadma
Published: September 2023

Purpose

With every successful organization embracing various facets of diversity in this new era, one such facet that is lesser talked about but has huge potential to bring organizational success is “Generational Diversity.” This paper emphasizes the significance of multiple generations in the workplace and suggests organization led strategies for achieving the benefits of generational diversity.

Design/methodology/approach

This paper draws on extant literature and knowledge in the field of generational diversity. By reviewing the characteristics, values, work styles and perspectives of multiple generations, this paper offer several strategies to successfully manage and leverage generational diversity.

Findings

This paper provides an overview of generational diversity and insights on its relevance at workplace. Besides, it also enlists and emphasizes eight different strategies that can help the organizations embrace and leverage the strengths of multiple generations at workplace.

Practical implications

Diversity & Inclusion (D&I) teams responsible for nurturing a diverse and inclusive culture at work can design and implement the strategies specified in this paper as per the suitability of their cohort(s) of employees to achieve the benefits of multigenerational workforce in organizations.

Originality/value

Generational diversity at workplace is an important factor toward achieving organizational success. For organizations with age-diverse workforce driving relentlessly toward success, there is a need to design and implement customized strategies and practices for managing multiple generations successfully. This study attempts to address this need by highlighting several organization led strategies to manage multiple generations successfully at workplace.