bluuebunny/crossref_metadata_2025 huggingface dataset:
Valsartan, Losartan and Irbesartan use in the USA, UK, Canada and Denmark after the nitrosamine recalls: a descriptive cohort study
Authors: Eworuke Efe , Shinde Mayura , Hou Laura , Paterson Michael J , Jensen Peter Bjødstrup , Maro Judith C , Rai Ashish , Scarnecchia Daniel , Pennap Dinci , Woronow Daniel , Ghosh Rebecca E , Welburn Stephen , Pottegard Anton , Platt Robert W , Lee Hana , Bradley Marie C
Published: April 2023

Objectives

To examine valsartan, losartan and irbesartan usage and switching patterns in the USA, UK, Canada and Denmark before and after July 2018, when the first Angiotensin-Receptor-Blocker (ARB) (valsartan) was recalled.

Design

Retrospective cohort study.

Setting

USA, Canadian administrative healthcare data, Danish National Prescription Registry and UK primary care electronic health records.

Participants

Patients aged 18 years and older between January 2014 and December 2020.

Intervention

Valsartan, losartan and irbesartan.

Main outcome

Monthly percentages of individual ARB episodes, new users and switches to another ARB, ACE inhibitors (ACEI) or calcium channel blockers containing products.

Results

We identified 10.8, 3.2, 1.8 and 1.2 million ARB users in the USA, UK, Canada and Denmark, respectively. Overall proportions of valsartan, losartan and irbesartan use were 18.4%, 67.9% and 5.2% in the USA; 3.1%, 48.3% and 10.2% in the UK, 16.3%, 11.4% and 18.3% in Canada, 1%, 93.5% and 0.6% in Denmark. In July 2018, we observed an immediate steep decline in the proportion of valsartan use in the USA and Canada. A similar trend was observed in Denmark; however, the decline was only minimal. We observed no change in trends of ARB use in the UK. Accompanying the valsartan decline was an increase in switching to other ARBs in the USA, Canada and Denmark. There was a small increase in switching to ACEI relative to the valsartan-to-other-ARBs switch. We also observed increased switching from other affected ARBs, losartan and irbesartan, to other ARBs throughout 2019, in the USA and Canada, although the usage trends in the USA remained unchanged.

Conclusion

The first recall notice for valsartan resulted in substantial decline in usage due to increased switching to other ARBs. Subsequent notices for losartan and irbesartan were also associated with increased switching around the time of the recall, however, overall usage trends remained unchanged.
Personalised recommendations for hospitalised patients with Acute Kidney Injury using a Kidney Action Team (KAT-AKI): protocol and early data of a randomised controlled trial
Authors: Aklilu Abinet Mathias , O’Connor Kyle D , Martin Melissa , Yamamoto Yu , Coronel-Moreno Claudia , Shvets Kristina , Jones Charles , Kadhim Bashar , Corona-Villalobos Celia P , Baker Megan L , Tan Jiawei , Freeman Natasha , Groener Marwin , Menez Steven , Brown Dannielle , Culli Samuel E , Lindsley John , Orias Marcelo , Parikh Chirag , Smith Abigail , Sundararajan Anusha , Wilson Francis P
Published: April 2023

Introduction

Although studies have examined the utility of clinical decision support tools in improving acute kidney injury (AKI) outcomes, no study has evaluated the effect of real-time, personalised AKI recommendations. This study aims to assess the impact of individualised AKI-specific recommendations delivered by trained clinicians and pharmacists immediately after AKI detection in hospitalised patients.

Methods and analysis

KAT-AKI is a multicentre randomised investigator-blinded trial being conducted across eight hospitals at two major US hospital systems planning to enrol 4000 patients over 3 years (between 1 November 2021 and 1 November 2024). A real-time electronic AKI alert system informs a dedicated team composed of a physician and pharmacist who independently review the chart in real time, screen for eligibility and provide combined recommendations across the following domains: diagnostics, volume, potassium, acid–base and medications. Recommendations are delivered to the primary team in the alert arm or logged for future analysis in the usual care arm. The planned primary outcome is a composite of AKI progression, dialysis and mortality within 14 days from randomisation. A key secondary outcome is the percentage of recommendations implemented by the primary team within 24 hours from randomisation. The study has enrolled 500 individuals over 8.5 months. Two-thirds were on a medical floor at the time of the alert and 17.8% were in an intensive care unit. Virtually all participants were recommended for at least one diagnostic intervention. More than half (51.6%) had recommendations to discontinue or dose-adjust a medication. The median time from AKI alert to randomisation was 28 (IQR 15.8–51.5) min.

Ethics and dissemination

The study was approved by the ethics committee of each study site (Yale University and Johns Hopkins institutional review board (IRB) and a central IRB (BRANY, Biomedical Research Alliance of New York). We are committed to open dissemination of the data through clinicaltrials.gov and sharing of data on an open repository as well as publication in a peer-reviewed journal on completion.

Trial registration number

NCT04040296.
Comparing relationships between single types of adverse childhood experiences and health-related outcomes: a combined primary data study of eight cross-sectional surveys in England and Wales
Authors: Bellis Mark A , Hughes Karen , Cresswell Katie , Ford Kat
Published: April 2023

Objectives

Adverse childhood experiences (ACEs) show strong cumulative associations with ill-health across the life course. Harms can arise even in those exposed to a single ACE type but few studies examine such exposure. For individuals experiencing a single ACE type, we examine which ACEs are most strongly related to different health harms.

Design

Secondary analysis of combined data from eight cross-sectional general population ACE surveys.

Setting

Households in England and Wales.

Participants

20 556 residents aged 18–69 years.

Measures

Ten self-reported outcomes were examined: smoking, cannabis use, binge drinking, obesity, sexually transmitted infection, teenage pregnancy, mental well-being, violence perpetration, violence victimisation and incarceration. Adjusted ORs and percentage changes in outcomes were calculated for each type of ACE exposure.

Results

Significance and magnitude of associations between each ACE and outcome varied. Binge drinking was associated with childhood verbal abuse (VA), parental separation (PS) and household alcohol problem (AP), while obesity was linked to sexual abuse (SA) and household mental illness. SA also showed the biggest increase in cannabis use (25.5% vs 10.8%, no ACEs). Household AP was the ACE most strongly associated with violence and incarceration. PS was associated with teenage pregnancy (9.1% vs 3.7%, no ACEs) and 5 other outcomes. VA was associated with 7 of the 10 outcomes examined.

Conclusion

Exposure to a single ACE increases risks of poorer outcomes across health-harming behaviours, sexual health, mental well-being and criminal domains. Toxic stress can arise from ACEs such as physical and SA but other more prevalent ACEs (eg, VA, PS) may also contribute substantively to poorer life course health.
End of life in haematology: quality of life predictors – retrospective cohort study
Authors: Korsos Victoria , Ali Alla'a , Malagon Talia , Khosrow-Khavar Farzin , Thomas Doneal , Sirhan Shireen , Davison Kelly , Assouline Sarit , Cassis Chantal
Published: April 2023

Objectives

Haematology patients are more likely to receive high intensity care near end of life (EOL) than patients with solid malignancy. Previous authors have suggested indicators of quality EOL for haematology patients, based on a solid oncology model. We conducted a retrospective chart review with the objectives of (1) determining our performance on these quality EOL indicators, (2) describing the timing of level of intervention (LOI) discussion and palliative care (PC) consultation prior to death and (3) evaluating whether goals of therapy (GOT), PC consultation and earlier LOI discussion are predictors of quality EOL.

Methods

We identified patients who died from haematological malignancies between April 2014 and March 2016 (n=319) at four participating McGill University hospitals and performed retrospective chart reviews.

Results

We found that 17% of patients were administered chemotherapy less than 14 days prior to death, 20% of patients were admitted to intensive care, 14% were intubated and 5% were resuscitated less than 30 days prior to death, 18% of patients received blood transfusion less than 7 days prior to death and 67% of patients died in an acute care setting. LOI discussion and PC consultation occurred a median of 22 days (IQR 7–103) and 9 days (IQR 3–19) before death. Patients with non-curative GOT, PC consultation or discussed LOI were significantly less likely to have high intensity EOL outcomes.

Conclusions

In this study, we demonstrate that LOI discussions, PC consults and physician established GOT are associated with quality EOL outcomes for patients with haematological malignancies.
GROWTH AND CHARACTERIZATION OF POLYMERIC MEMBRANE MODIFIED BY MAGNETIC NANOPARTICLES
Authors: KHALID S. , SHAMAILA S. , RAZA M. , ASHRAF S. , TOHEED A.
Published: April 2023

In this study, we aimed to modify polymeric membranes by incorporating magnetic nanoparticles (NPs) to enhance their properties. The structural and chemical properties of magnetic NPs of iron oxide were prepared via a wet chemical method. Iron oxide nanoparticles (IONPs) were used as the core and were coated with polymers polyvinyle alcohol (PVA) and polyvinylpyrrolidone (PVP). The prepared samples were cast on a glass substrate using a casting knife. The aim of this study is the use of a specific type of magnetic NPs, coated with a polymer, and their application in membrane modification. We employed a facile synthesis method to coat the IONPs with the polymer and characterized the resulting material using various techniques, including X-ray Diffraction (XRD), scanning electron microscope (SEM), Fourier Transform Infrared (FTIR) Spectroscopy, and UV/Visible (UV–Vis) Spectroscopy for structural, morphological, chemical bonding, and optical properties studies. Our results show that the modified polymeric membranes exhibited improved properties, such as increased permeability and selectivity. We also observed that the magnetic NPs helped in the easy recovery of the modified membranes using an external magnetic field. Some agglomeration of IONPs was also observed, and the polymer membrane caused a decrease in crystallinity of IONPs. Overall, this study presents a promising approach for enhancing the properties of polymeric membranes using magnetic NPs and can potentially have practical applications in various fields, such as water treatment, food processing, and biotechnology.
Re-Evaluating the Major Factors in the Low Origination Rate of the Reverse Mortgage Market
Authors: Liu Wei-Han
Published: April 2023

We reinvestigate the major factors in the low origination rate of home equity conversion mortgages (HECMs) in the United States from 2010 to 2017. We use panel data analysis to consider the variation in time and region and investigate the main determinants of the HECM origination rate. We examine five categories of variables: demographics, home equity, home debt level, retirement income, and taxes. We first filter out key variables and then consider the interactions among these factors. The empirical outcomes confirm the significance of including interactions and provide detailed observations to resolve several disputed issues and make policy recommendations, such as debt priority of mortgage and credit card, applying HECM as a personal or household decision, and the dominance of property tax over inheritance tax.
Deformations of 𝔞𝔣𝔣(n|1)-module of weighted densities on ℝ1|n, n ≥ 2
Authors: Faidi S. , Faidi T.
Published: April 2023

Over the [Formula: see text]-dimensional real superspace, [Formula: see text], we study non-trivial deformations of the natural action of the affine Lie superalgebra [Formula: see text] on the direct sum of the superspaces of weighted densities. We compute the necessary and sufficient integrability conditions of a given infinitesimal deformation of this action and we prove that any formal deformation is equivalent to its infinitesimal part. This work is the simplest generalization of a result by Basdouri and Omri [Cohomology and deformation of [Formula: see text] acting on differential operators, Int. J. Geom. Methods Mod. Phys. 15 (2018) 1850072].
History and recent progress in ferroelectrets produced in Brazil
Authors: Altafim Ruy Alberto Pisani , Altafim Ruy Alberto Corrêa
Published: April 2023

More than 30 years ago, a group of researchers in Tampere–Finland developed a thin foamed polymeric material for capacitive sensors. Such soft-voided films exhibited electrical charging characteristics, forming a powerful combination, which resulted in a smart-material with ferroelectric properties. The discovery of the electro-thermo mechanical film (ETMF) has sparked the curiosity of the electret community, leading to the development of several studies. At that time, ETMF became known as cellular electrets and, later, as ferroelectrets or piezoelectrets regarding their electromechanical properties. This paper provides a timeline review of the research on ferroelectrets produced in Brazil, between the years 1990 and 2020, towards demonstrating how the interest in the electret electrical charging mechanism has resulted in the use of ferroelectrets with well-controlled cavities for ultrasound applications.
A Walk in Time and Space: My Journey as a Strategic Scientist
Authors: Ye Shuhua
Published: April 2023

This article depicts my life and career over the past decades, beginning with my birth in 1927 and ending in my two dreams yet to be realized. This article focuses on my school years during wartime and my work with Shanghai Astronomical Observatory (SHAO) of the Chinese Academy of Sciences (CAS) from 1951 on—serving as Director of SHAO during 1981–1993 and a Member of CAS since 1980—and shares some social activities I've been involved in for the benefits of women and children. Special focus is given to the endeavors of building one of the world's most precise Universal Time systems in the 1960s, a very long baseline interferometry network, a satellite laser ranging research station during the 1970s–1990s, and the 65-m Radio Telescope in the early twenty-first century; developing astro-geodynamics in China and advancing the Asia-Pacific Space Geodynamics Program in the late twentieth century; and leading SHAO in international cooperation while serving as Chair of the International Astronomical Union Finance Committee during 1985–1988, the IAU Vice-President during 1988–1994, and a foreign fellow of the Royal Astronomical Society of Britain in 1985. This autobiographical account should, hopefully, serve its purpose of offering a glimpse of me and my lifelong interaction with time and space.
Thinking Beyond the Device: An Overview of Human- and Equity-Centered Approaches for Health Technology Design
Authors: Rodriguez Natalia M. , Burleson Grace , Linnes Jacqueline C. , Sienko Kathleen H.
Published: April 2023

A shift in the traditional technocentric view of medical device design to a human-centered one is needed to bridge existing translational gaps and improve health equity. To ensure the successful and equitable adoption of health technology innovations, engineers must think beyond the device and the direct end user and must seek a more holistic understanding of broader stakeholder needs and the intended context of use early in a design process. The objectives of this review article are ( a) to provide rationale for the need to incorporate meaningful stakeholder analysis and contextual investigation in health technology development and biomedical engineering pedagogy, ( b) to review existing frameworks and human- and equity-centered approaches to stakeholder engagement and contextual investigation for improved adoption of innovative technologies, and ( c) to present case studyexamples of medical device design that apply these approaches to bridge the gaps between biomedical engineers and the contexts for which they are designing.
Changes of Peripapillary Capillary Density in Patients with Vogt–Koyanagi–Harada Disease Evaluated by Optical Coherence Tomography Angiography
Authors: Jiang Zhijian , Ji Huiying , Zhang Nan , Huang Liang , Zhou Min , Dong Jianhong
Published: April 2023

Objective. To analyze the longitudinal changes in peripapillary capillary density in patients with acute VKH with or without optic disc swelling by optical coherence tomography angiography (OCTA). Methods. Retrospective case series. 44 patients (88 eyes) were enrolled and were divided into two groups according to presence/absence of optic disc swelling before treatment. Peripapillary capillary images were obtained by OCTA before and after 6 months of corticosteroid treatment and used to determine the radial peripapillary capillary (RPC), retinal plexus, and choriocapillaris vessel perfusion densities. Results. Optic disc swelling was present in 12 patients (24 eyes) and absent in 32 patients (64 eyes). The sex distribution, age, intraocular pressure, and best‐corrected visual acuity before and after treatment were not significantly different between the two groups (all P > 0.05). Compared to those in nonoptic disc swelling group, the percentages of decreased vessel perfusion densities after treatment in the supranasal (RPC, 100.00% vs. 75.00%), infranasal (RPC, 100.00% vs. 56.25%), infratemporal (RPC, 66.67% vs. 37.50%), and infranasal quadrants (retinal plexus, 83.33% vs. 56.25%) were significantly more in optic disc swelling group. The choriocapillaris vessel perfusion density increased after treatment in both groups. Conclusions. Decreases in vessel perfusion densities of the RPC and retinal plexus after treatment in VKH patients with optic disc swelling were more common than in those without optic disc swelling. The choriocapillaris vessel perfusion density increased after treatment, regardless of the presence/absence of optic disc swelling.
Development of an Effective Acne Treatment Based on CBD and Herbal Extracts: Preliminary In Vitro, Ex Vivo, and Clinical Evaluation
Authors: Cohen Guy , Jakus Jeannette , Baroud Sumer , Gvirtz Raanan , Rozenblat Sharon
Published: April 2023

Acne vulgaris, the most common form of acne, is characterized by a mixed eruption of inflammatory and noninflammatory skin lesions primarily affecting the face, upper arms, and trunk. The pathogenesis of acne is multifactorial and includes abnormal keratinization and plugging of the hair follicles, increased sebum production, proliferation and activation of Cutibacterium acnes (C. acnes; formerly Propionibacterium acnes, P. acnes), and finally inflammation. Recent studies have found that cannabidiol (CBD) may be beneficial in the treatment of acne. The aim of this study was to explore natural plant extracts that, when combined with CBD, act synergistically to treat acne by targeting different pathogenic factors while minimizing side effects. The first stage of the study investigated the capacity of different plant extracts and plant extract combinations to reduce C. acnes growth and decrease IL‐1β and TNFα secretion from U937 cells. The results found that Centella asiatica triterpene (CAT) extract as well as silymarin (from Silybum marianum fruit extract) had significantly superior anti‐inflammatory activity when combined with CBD compared to either ingredient alone. In addition, the CAT extract helped potentiate CBD‐induced C. acnes growth inhibition. The three ingredients were integrated into a topical formulation and evaluated in ex vivo human skin organ cultures. The formulation was found to be safe and effective, reducing both IL‐6 and IL‐8 hypersecretion without hampering epidermal viability. Finally, a preliminary clinical study of this formulation conducted on 30 human subjects showed a statistically significant reduction in acne lesions (mainly inflammatory lesions) and porphyrin levels, thereby establishing a tight correlation between in vitro, ex vivo, and clinical results. Further studies must be conducted to verify the results, including placebo‐controlled clinical assessment, to exclude any action of the formulation itself.
The Discrete Load Frequency Control System Using a Robust Periodic Output Feedback Controller
Authors: Kumawat Hukam Chand , Bhadu Mahendra , Kumar Arvind , Mahela Om Prakash , Khan Baseem , Anand Divya , Breñosa Jose
Published: April 2023

The load frequency control (LFC) is a most important tool for the frequency regulation mechanism in the widely spread modern power system. The LFC system consists of a communication structure to transmit the measurement and control signal. Usually the controllers in LFC systems are designed and implemented in continuous mode of operation. This article investigates the discrete mode load frequency control (LFC) mechanism, by employing the concept of the periodic output feedback (POF)-based controller with varying input and output sampling frequencies. Both the optimal sampling frequency and the optimal POF controller gain matrix are found by using the particle swarm optimization (PSO) method. The POF-based controller is intended for usage in two-area multisource LFC systems, with varying input and output sampling frequencies. The performance analysis takes into account a variety of scenarios, including those without a conventional stabilizer, with conventional continuous and corresponding discrete mode PSS, and a proposed discrete mode POF controller. Furthermore, the efficacy of the discrete mode POF controller is evaluated on the MATLAB/Simulink platform.
Numerical Analysis of the Stress Distribution and Concentration Factors of the Tool Joint of the Directional Drill Pipe
Authors: Shu Jiangjun , Zhang Yu , Zhao Zhiqiang , Mei Anping , Liu Li
Published: April 2023

With the wide application of directional drilling technology in coal mine predraining boreholes, the failure problem of the tool joint of the directional drill pipe has become one of the main factors restricting the drilling efficiency. The main reason for the failure problem of the tool joint of the directional drill pipe is the stress concentration. The stress test rig for the tool joint of the directional drill pipe is designed based on the resistance strain measurement method, and the stress of the tool joint of the directional drill pipe is tested. The tool joint’s 3D finite element model was established based on nonlinear contact theory. The experiment verified the accuracy of this model. The stress distribution of the tool joint of the directional drill pipe was obtained. The research shows that the stress of the tool joint of the directional drill pipe is concentrated at the root between the third and the fourth turn of the engaged thread. The work presented in this study is a reliable guide to the design and field use of the tool joint of the directional drill pipe.
Bilateral Lipid Keratopathy in the Setting of Brimonidine Tartrate Use
Authors: Moshirfar Majid , Ziari Melody , Payne Carter J. , Stapley Seth R. , Ply Briana K. , Ronquillo Yasmyne C. , Hoopes Phillip C.
Published: April 2023

Lipid keratopathy (LK) is a rare disease involving lipid deposition in the cornea resulting in corneal opacification. Primary LK can arise sporadically while secondary LK is seen in patients with a history of ocular trauma, medication exposure, infection, inflammation, or disorders resulting in derangements of lipid metabolism. Secondary LK is more common and occurs due to neovascularization. Use of precipitating medications should be considered in LK workup, particularly for patients in whom other etiologies have been ruled out. Brimonidine, an ocular hypotensive medication, can be associated with LK. We present a case of bilateral secondary LK in a patient with a history of prolonged brimonidine use, without additional contributing factors.
A Novel Hybrid Framework to Enhance Dual‐Energy X‐Ray Images
Authors: Ullah Burhan , Khan Aurangzeb , Shah Said Khalid , Su’ud Mazliham Mohd , Alam Muhammad Mansoor , Alam Mahmood
Published: April 2023

This research paper presents an efficient hybrid framework for the enhancement of X‐ray images using the DWT (discrete wavelet transform), Gaussian, and Wiener filters. Digital X‐ray images perform an important role in detecting explosives or illegal items. However, lately used X‐ray images have certain shortcomings like noise, blurriness, and low contrast. Noise affects the object’s edges and values of intensity of pixels which gives rise to ambiguity for the system to separate objects and also hampers the decision‐making process. To overcome these issues, a new hybrid framework is proposed here that consists of two layers. First, it reads high‐ and low‐energy X‐ray images and fuses them through various fusion rules in the wavelet realm using DWT and is reconstructed using iDWT (inverse discrete wavelet transform). Subsequently, the Gaussian filter is applied to the fused image to remove the Gaussian noise, and finally, the Wiener filter is used to reduce blurriness and improve image quality. The quality of the image is measured using PSNR (peak signal‐to‐noise ratio) and MSE (mean squared error) values, which exhibits that an average of the MSE values of fused images is 40% lower, and the PSNR values are 10% higher than the single images. Experimental results show that this hybrid framework successfully reduced noise and blurriness and enhanced contrast and accuracy.
Single-Cell Spatial Analysis Identifies Regulators of Brain Tumor–Initiating Cells
Authors: Mirzaei Reza , D'Mello Charlotte , Liu Marina , Nikolic Ana , Kumar Mehul , Visser Frank , Bose Pinaki , Gallo Marco , Yong V. Wee
Published: April 2023

Glioblastomas (GBM) are aggressive brain tumors with extensive intratumoral heterogeneity that contributes to treatment resistance. Spatial characterization of GBMs could provide insights into the role of the brain tumor microenvironment in regulating intratumoral heterogeneity. Here, we performed spatial transcriptomic and single-cell analyses of the mouse and human GBM microenvironment to dissect the impact of distinct anatomical regions of brains on GBM. In a syngeneic GBM mouse model, spatial transcriptomics revealed that numerous extracellular matrix (ECM) molecules, including biglycan, were elevated in areas infiltrated with brain tumor–initiating cells (BTIC). Single-cell RNA sequencing and single-cell assay for transposase-accessible chromatin using sequencing showed that ECM molecules were differentially expressed by GBM cells based on their differentiation and cellular programming phenotypes. Exogeneous biglycan or overexpression of biglycan resulted in a higher proliferation rate of BTICs, which was associated mechanistically with low-density lipoprotein receptor-related protein 6 (LRP6) binding and activation of the Wnt/β-catenin pathway. Biglycan-overexpressing BTICs developed into larger tumors and displayed mesenchymal phenotypes when implanted intracranially in mice. This study points to the spatial heterogeneity of ECM molecules in GBM and suggests that the biglycan–LRP6 axis could be a therapeutic target to curb tumor growth.

Significance:

Characterization of the spatial heterogeneity of glioblastoma identifies regulators of brain tumor–initiating cells and tumor growth that could serve as candidates for therapeutic interventions to improve the prognosis of patients.
Li–Fraumeni Syndrome–Associated Dimer-Forming Mutant p53 Promotes Transactivation-Independent Mitochondrial Cell Death
Authors: Choe Joshua H. , Kawase Tatsuya , Xu An , Guzman Asja , Obradovic Aleksandar Z. , Low-Calle Ana Maria , Alaghebandan Bita , Raghavan Ananya , Long Kaitlin , Hwang Paul M. , Schiffman Joshua D. , Zhu Yan , Zhao Ruiying , Lee Dung-Fang , Katz Chen , Prives Carol
Published: April 2023

Cancer-relevant mutations in the oligomerization domain (OD) of the p53 tumor suppressor protein, unlike those in the DNA binding domain, have not been well elucidated. Here, we characterized the germline OD mutant p53(A347D), which occurs in cancer-prone Li–Fraumeni syndrome (LFS) patients. Unlike wild-type p53, mutant p53(A347D) cannot form tetramers and exists as a hyperstable dimeric protein. Further, p53(A347D) cannot bind or transactivate the majority of canonical p53 target genes. Isogenic cell lines harboring either p53(A347D) or no p53 yield comparable tumorigenic properties, yet p53(A347D) displays remarkable neomorphic activities. Cells bearing p53(A347D) possess a distinct transcriptional profile and undergo metabolic reprogramming. Further, p53(A347D) induces striking mitochondrial network aberration and associates with mitochondria to drive apoptotic cell death upon topoisomerase II inhibition in the absence of transcription. Thus, dimer-forming p53 demonstrates both loss-of-function (LOF) and gain-of-function (GOF) properties compared with the wild-type form of the protein.

Significance:

A mutant p53 (A347D), which can only form dimers, is associated with increased cancer susceptibility in LFS individuals. We found that this mutant wields a double-edged sword, driving tumorigenesis through LOF while gaining enhanced apoptogenic activity as a new GOF, thereby yielding a potential vulnerability to select therapeutic approaches.

See related commentary by Stieg et al., p. 1046.

See related article by Gencel-Augusto et al., p. 1230.

This article is highlighted in the In This Issue feature, p. 1027
Opportunities for Achieving the Cancer Moonshot Goal of a 50% Reduction in Cancer Mortality by 2047
Authors: Shiels Meredith S. , Lipkowitz Stanley , Campos Nicole G. , Schiffman Mark , Schiller John T. , Freedman Neal D. , Berrington de González Amy
Published: April 2023

On February 2, 2022, President Biden and First Lady Dr. Biden reignited the Cancer Moonshot, setting a new goal to reduce age-standardized cancer mortality rates by at least 50% over the next 25 years in the United States. We estimated trends in U.S. cancer mortality during 2000 to 2019 for all cancers and the six leading types (lung, colorectum, pancreas, breast, prostate, liver). Cancer death rates overall declined by 1.4% per year from 2000 to 2015, accelerating to 2.3% per year during 2016 to 2019, driven by strong declines in lung cancer mortality (−4.7%/year, 2014 to 2019). Recent declines in colorectal (−2.0%/year, 2010–2019) and breast cancer death rates (−1.2%/year, 2013–2019) also contributed. However, trends for other cancer types were less promising. To achieve the Moonshot goal, progress against lung, colorectal, and breast cancer deaths needs to be maintained and/or accelerated, and new strategies for prostate, liver, pancreatic, and other cancers are needed. We reviewed opportunities to prevent, detect, and treat these common cancers that could further reduce population-level cancer death rates and also reduce disparities.

Significance:

We reviewed opportunities to prevent, detect, and treat common cancers, and show that to achieve the Moonshot goal, progress against lung, colorectal, and breast cancer deaths needs to be maintained and/or accelerated, and new strategies for prostate, liver, pancreatic, and other cancers are needed.

See related commentary by Bertagnolli et al., p. 1049.

This article is highlighted in the In This Issue feature, p. 1027
Morphological Characteristics and Reproductive Organs Assessment of Blue-Spotted Mudskipper Boleophthalmus Boddarti in Peninsular Malaysia
Authors: Mohd Nor Nur-Hidayah , Saifuzzaman Syazwin-Rafhanah , Azmir Izzati Adilah , Hussin Norjasmin
Published: April 2023

Mudskippers have a unique adaptation allowing them to live on the land and commonly inhabiting the mangrove ecosystem. A fundamental study on the Blue-spotted mudskippers, Boleopthalamus boddarti were purposely to identify the species through morphometric and meristic characteristics, observation on the gonad organs as well as to correlate with their length-weight relationship. Collection of B. boddarti (n=72) from Matang Perak, Pendas Johor and Pekan Pahang was conducted using hand and net. Data collection on seventeen morphometric and seven meristics characters, length and weight, and pictorial documentation on male and female gonads were conducted. The means of each characteristic were estimated by using analysis of Variance (ANOVA) with P<0.05. The morphometric analysis found eye diameter and posterior dorsal fin ray count characteristics were significantly different (P<0.05) followed by five meristics characteristics except for anterior dorsal fin ray count and upper jaw teeth characteristics (F value ≥ 1.0). The mature gonad of female B. boddarti was found with an ovary in bright yellow coloration, turgid, firm and visible presence of eggs. Male gonads were identified with a testis having two lobes, a swollen structure at the top of the elongated shape and appear pale pink and thicker than the immature testes that generally exist in string-like structures. The length and weight of the fish were found directly proportional to the regression curve displayed b≠3. Morphometric and meristic characteristics were a reliable method in the identification of fish in general and for B. boddarti in specific. The observation of gonads differentiation helps understand the mature and immature state of the sex organs. This study offered an easy, quick and low-cost approach in determining species and sexes compared to the molecular method.
Identificaton and Diversity of Endophytic Fungi Associated with The Seagrasses of Cebu, Central Philippines
Authors: Kinamot Venus , Monotilla Alvin
Published: April 2023

Endophytic fungi were poorly documented in the marine environment, especially in seagrasses regardless of their importance as sources of novel metabolites. In the Philippines, studies are dearth despite having large areas of seagrass meadows. Thus, this study was conducted to isolate and identify endophytic fungi associated with common seagrasses: Enhalus acoroides, Cymodocea serrulata, and Thalassia hemprichii from the Philippines by morphologic and molecular methods. Seven species were identified in this study: Aspergillus tamarii, A. ochraceopetaliformis, A. sydowii, Penicillium citrinum, Xylaria sp., Beauveria bassiana, and Eutypella sp. Morphologically, Aspergillus spp. had septate hyphae, biseriate conidiophore, and smooth to rough globose conidia. Penicillium had a green colony, biverticillate conidiophore, and smooth, globose conidia. Beauveria bassiana had white to cream colonies with irregular edges and a powdery appearance. The conidiogenous cells had zigzag rachis in which a chain of conidia emerged. Eutypella sp. had white, filariform, and plumose colony. Xylaria sp. had a white colony with conspicuous radial lines and a plumose margin.  Phylogenetic analysis using 80 ITS rDNA sequences by neighbor-joining revealed the clustering of our isolates with the closest match taxa in the same clade with 100% bootstrap value. The estimate of evolutionary divergence between our isolates and their closest match taxa by pairwise distance showed no nucleotide base substitution suggesting high sequence identity between sequences. The most diverse endophyte is Aspergillus as it is ubiquitously adapted to the marine environment. To our knowledge, this is the first report of these species colonizing the seagrasses from the Philippines.
O sofrimento, a depressão e o impacto na autoimagem em indivíduos com queimaduras
Authors: Moraes Sandra Renata Pinatti de , Marcolan João Fernando
Published: April 2023

Resumo: Fundamentos: Indivíduos com queimaduras sofrem com autoestima e depressão. Objetivo: Analisar percepção dos participantes quanto ao sofrimento ocasionado pela queimadura, sintomatologia depressiva e interferência na autoimagem e relacionamento interpessoal. Métodos: Estudo qualitativo, longitudinal, descritivo, com 36 participantes atendidos em centro de referência a queimados de hospital escola do Sul do Brasil. Realizada entrevista semiestruturada, dados tratados pela Análise de Conteúdo. Resultados: Emergiu categoria sobre o sofrimento causado pela queimadura e impacto na autoimagem com três unidades temáticas. Dados apontam participantes insatisfeitos com autoimagem, desenvolveram sintomatologia depressiva em resposta as dificuldades que queimadura acarretou na vida de relação; apoio familiar foi decisivo ao enfrentamento da nova condição, relações afetivas foram resgatadas a beneficiar a recuperação. Conclusão e implicações para prática: Percepção dos participantes para autoimagem prejudicada associada a autoestima diminuída e sintomatologia depressiva, prejuízo para o relacionamento interpessoal e apontam a importância da família no processo de recuperação e fortalecimento dos laços familiares durante e após tratamento da queimadura.
Aspectos radiológicos do baço intrapancreático
Authors: Lima Luara Araújo Rodrigues , Gomes Raissa Fernanda Maciel , Sousa André Luca Araujo de , Pinto Antonione Santos Bezerra , Costa Vanessa da Conceição Soares , Oliveira Leonam Costa
Published: April 2023

Baço – acessório localizado dentro do parênquima pancreático – é uma anomalia congênita do tecido esplênico, com características morfológicas e histológicas semelhante ao baço normal apresentado, geralmente, na cauda do pâncreas. O baço acessório intrapancreático (BAI) trata-se, sobretudo, de uma lesão benigna, usualmente assintomática e encontrada incidentalmente em estudos de imagem, mas que suscitam frequentemente uma preocupação de malignidade e podem ser radiologicamente indistinguíveis de tumores neuroendócrinos, tumores pancreáticos e adenocarcinomas. O presente estudo visa, portanto, relatar um caso de baço acessório intrapancreático através da tomografia computadorizada (TC) e ressonância magnética (RM), além de correlacionar os achados radiográficos do relato de caso com outros métodos radiológicos encontrados na revisão de literatura. As informações contidas foram obtidas por meio de revisão do prontuário, entrevista com o paciente, registro fotográfico dos métodos diagnósticos em geral e dados laboratoriais, aos quais o paciente foi submetido. Nesse contexto, o relato de caso é de um homem com história prévia de carcinoma de células renais que, após realização de nefrectomia total à esquerda e de linfonodos retroperitoneais, constatou no seguimento de seus exames de controle pós-operatório uma imagem  nodular na cauda pancreática sugestiva de metástase, mas que, através do estudo tomográfico e de RM, foi possível realizar o correto diagnóstico, tratando-se apenas de uma afecção benigna assintomática e de intervenção conservadora descrita como BAI.
Consumption of medicinal plants and herbal medicines by children and adolescents with chronic conditions: a survey in a tertiary-care outpatient clinic
Authors: Inacio Raquel Fernanda Beraldo , Pereira Ana Maria Soares , Carmona Fabio
Published: April 2023

Objectives. Medicinal plants and herbal medicines are widely used worldwide. However, patients with chronic health conditions or their caregivers do not often disclose these practices to their healthcare providers, leading to potentially severe interactions with current treatments, especially in children. We aimed to describe the prevalence of the use of medicinal plants and herbal medicines by children and adolescents with chronic health conditions and whether their physicians were informed about it. Methods. We conducted a cross-sectional electronic survey on parents and caregivers of children and adolescents with chronic health conditions seen at a university, tertiary-care pediatric outpatient clinic. The common names of the plants cited by respondents were reviewed and Latin names of the species were provided whenever possible. Results. From 20,213 text messages sent in May and June 2021, 521 valid responses were obtained. The prevalence of the use of medicinal plants and herbal medicines was 34.6%, most without a medical prescription (self-medication), and few physicians (4.0%) were aware of it. The five most used species were: Mentha spicata L. (mint), Foeniculum vulgare Mill. (fennel), “cidreira” (a common name possibly corresponding to Cymbopogon citratus (DC.) Stapf, Melissa officinalis L. or Lippia alba (Mill.) N.E. Br. ex Britton & Wilson, P.), Matricaria chamomilla L. (German chamomile), and Plectranthus barbatus Andrews (boldo). Conclusions. The prevalence of the use of medicinal plants and herbal medicines by children and adolescents with chronic health conditions in a tertiary-care outpatient clinic was 34.6%, and only a few physicians were aware of it.
Deaths by COVID-19 in a hospital from a city from Legal Amazon region: what lessons could be learned?
Authors: Pessoa Fabrício Silva , Martins Helena Beatriz Moura , Rocha Neta Agostinha Pereira , Martins Andinilde Nogueira , Aragão Francisca Bruna Arruda , Rêgo Adriana Sousa , Souza Givago da Silva , Silva Luís Cláudio Nascimento da , Bomfim Maria Rosa Quaresma , Lacerda Eliza Maria da Costa Brito
Published: April 2023

Objectives: Describe the epidemiology of COVID-19 deaths within a hospital in the Amazon region in a period of 64 days, which corresponds to the growth curve of the COVID-19 first-wave pandemic in 2020.
Methods: The data were obtained from medical records of 152 deaths registered for adults and elderly hospitalized. The data were also compared with the number of deaths in previous years during the same period studied to assess the impact of the pandemic on this hospital. The study also assesses the impact of intra-hospital transfers, accounting for the number of times patients who died performed transfers between sectors of the hospital.
Results: During the period analyzed, there was an increase in deaths compared to the previous years. The majority of dead patients were male, aged between 34 and 96 years. The deaths were associated comorbidities such as arterial hypertension, diabetes mellitus, and kidney disease. The SARS-CoV-2 infection was confirmed in 91 cases. Among them, 15 individuals were admitted without conditions related to SARS-CoV-2 infection; they had a three-fold higher number of hospital transfers than those admitted with SARS-CoV-2 infection symptoms. Sixteen patients with SARS-CoV-2 infection developed respiratory symptoms just after hospitalization. The diagnostic exam for SARS-CoV-2 infection was performed on average 4 (± 6) days after the onset of symptoms and 6 (± 6) days after admission, and the average time from the onset of respiratory symptoms to death was 4 (± 6) days.
Conclusions: These data suggest the high presence of hospital infection by SARS-CoV-2 in the Brazilian Amazon region, which may be related to the number of sectorial transfers, delay in confirming the diagnosis, and lack of management. We report a serious public health problem, as it demonstrates the fragility of healthcare institutions in the hospital environment.
Relationship between vitamin B12 levels and insulin resistance in postmenopausal women from Colombia Caribbean
Authors: Sarmiento-Rubiano Luz Adriana , Becerra Jimmy Everth , Rebolledo-Cobos Roberto Carlos , Ortega-Ariza Norella , Sarmiento-Rubiano María Cristina
Published: April 2023

Introduction: The high prevalence of low vitamin B12 serum levels has been recognized as a public health problem in Latin America; however, the current magnitude of this deficiency in Colombia is uncertain. Low levels of vitamin B12 can induce clinical and subclinical hematological and neurological disorders. Epidemiological studies have demonstrated a relationship between vitamin B12 deficiency and cardiovascular diseases (CVDs). However, the role of vitamin B12 in insulin resistance has been poorly studied. Objective: This study aimed to evaluate the relationship between vitamin B12 serum levels and biochemical and anthropometric markers related to CVDs and insulin resistance in postmenopausal women from Colombia Caribbean. Methods: Correlational, descriptive study. By convenience sampling, 182 postmenopausal women from the medical consultation service of a health institution were linked. Serum vitamin B12 levels, anthropometric variables (body mass index, abdominal perimeter), and biochemical variables (glycemia, insulin, lipid profile, HOMA IR) were evaluated. Results: The average value of the vitamin B12 serum level was 312.5 ± 122.5 pg/mL (230.6 ± 90.4 pmol/L); 46.7% of the women had less than adequate levels of 300 pg/mL (> 221 pmol/L), and 9. 9% were deficient, with levels of less than 200 pg/mL (148 pmol/L). The women with metabolic syndrome were 63.7%, and according to HOMA IR, 52.7 % had insulin resistance. A significant inverse relationship was shown between serum vitamin B12 levels with basal glycemic (P =0.002) and HOMA-IR (P =0.040). Conclusions: A significant inverse relationship between vitamin B12 levels and basal glycemia and HOMA-IR was observed. These findings highlight vitamin B12 deficiency in postmenopausal women and suggest nutritional supplementation.
Sensory remapping: a possible therapy option
Authors: Sousa Wanderson Silva Macedo de , Lemos Matheus Sam do Santos , Silva Diego Agripino Chagas , Leite Therezza Inácia Martins Gomes , Adad Ana Claúdia de Miranda , Sousa Ana Flávia Ferreira , Araújo Gabriela Veiga Macedo e , Ribeiro Jonatas Paulino da Cunha Monteiro
Published: April 2023

The human sensory receptors are morphologically specialized to transduce specific stimuli into the brain. However, when an injury occurs, mainly in the spinal cord, which can be of traumatic or non-traumatic origin, it provokes various degrees of sensory deficits, autonomic, motor and sphincter dysfunction below the level of the injury. Based on this, a new therapeutic modality is being proposed by neuroscientist Miguel Nicolelis, which is based on the brain-machine interface, that is, using other pathways so that the information can reach the cerebral cortex and thus be consciously processed.
Cluster de doenças crônicas não transmissíveis e multimorbidade em trabalhadores da atenção primária à saúde
Authors: Mendes Flávio Gabriel Barbosa , Rocha Saulo Vasconcelos , Oliveira Juliana da Silva , Ferreira Bruna Maria Palotino , Conceição Ariani França
Published: April 2023

Objetivo: Investigar a agregação das DCNT e a sua associação com as características sociodemográficas e os aspectos ocupacionais dos trabalhadores da APS. Métodos: Tratou-se de um estudo epidemiológico transversal que analisou os dados parciais de uma coorte retrospectiva realizada em Vitória da Conquista (BA) e em São Geraldo da Piedade (MG) no mês de janeiro de 2022 com 105 trabalhadores da Estratégia Saúde da Família (ESF), que preencheram um questionário eletrônico específico autoaplicável. As variáveis analisadas foram: sociodemográficas, caracterização do trabalho, presença de DCNT e de multimorbidade. Foram aplicados os seguintes procedimentos estatísticos: análise descritiva, análise de cluster, teste de qui-quadrado de Pearson e regressão logística binária. Resultados: As cinco DCNT mais prevalentes foram a rinite/sinusite (30,5%), a cefaleia/enxaqueca (26,7%), o colesterol alto (26,7%), a gastrite (19,0%) e a hipertensão arterial sistêmica (19,0%). A prevalência de multimorbidade foi de 26,7% e foram encontradas 11 combinações de cluster (34,4%), sendo o maior escore na combinação das cinco doenças mais prevalentes. Foi identificada a associação entre a presença de multimorbidade e o sexo, sendo a prevalência 24% menor entre os homens, e com a escolaridade, sendo a prevalência 26% maior nos indivíduos que não possuem ensino superior. Conclusão: Foram identificadas associações entre a presença de multimorbidade e o sexo feminino, e indivíduos que não concluíram o ensino superior. Observou-se, ainda, uma associação simultânea das cinco principais DCNT deste estudo com o nível de escolaridade.