bluuebunny/crossref_metadata_2025_split huggingface dataset:
The multiple roles of lysophosphatidic acid in vascular disease and atherosclerosis
Authors: Chattopadhyay Arnab , Reddy Srinivasa T. , Fogelman Alan M. 
Published: July 2023

Purpose of review
To explore the multiple roles that lysophosphatidic acid (LPA) plays in vascular disease and atherosclerosis.

Recent findings
A high-fat high-cholesterol diet decreases antimicrobial activity in the small intestine, which leads to increased levels of bacterial lipopolysaccharide in the mucus of the small intestine and in plasma that increase systemic inflammation, and enhance dyslipidemia and aortic atherosclerosis. Decreasing LPA production in enterocytes reduces the impact of the diet. LPA signaling inhibits glucagon-like peptide 1 secretion, promotes atherosclerosis, increases vessel permeability and infarct volume in stroke, but protects against abdominal aortic aneurysm formation and rupture. Acting through the calpain system in lymphatic endothelial cells, LPA reduces the trafficking of anti-inflammatory Treg lymphocytes, which enhances atherosclerosis. Acting through LPA receptor 1 in cardiac lymphatic endothelial cells and fibroblasts, LPA enhances hypertrophic cardiomyopathy.

Summary
LPA plays multiple roles in vascular disease and atherosclerosis that is cell and context dependent. In some settings LPA promotes these disease processes and in others it inhibits the disease process. Because LPA is so ubiquitous, therapeutic approaches targeting LPA must be as specific as possible for the cells and the context in which the disease process occurs.
Mechanical ventilation during pediatric extracorporeal life support
Authors: Kneyber Martin C.J. , Cheifetz Ira M. 
Published: July 2023

Purpose of review
To discuss the role of ventilator induced lung injury (VILI) and patient self-inflicted lung injury in ventilated children supported on extracorporeal membrane oxygenation (ECMO).

Recent findings
While extracorporeal life support is used routinely used every day around the globe to support neonatal, pediatric, and adult patients with refractory cardiac and/or respiratory failure, the optimal approach to mechanical ventilation, especially for those with acute respiratory distress syndrome (ARDS), remains unknown and controversial. Given the lack of definitive data in this population, one must rely on available evidence in those with ARDS not supported with ECMO and extrapolate adult observations. Ventilatory management should include, as a minimum standard, limiting inspiratory and driving pressures, providing a sufficient level of positive end-expiratory pressure, and setting a low rate to reduce mechanical power. Allowing for spontaneous breathing and use of pulmonary specific ancillary treatment modalities must be individualized, while balancing the risk and benefits. Future studies delineating the best strategies for optimizing MV during pediatric extracorporeal life support are much needed.

Summary
Future investigations will hopefully provide the needed evidence and better understanding of the overall goal of reducing mechanical ventilation intensity to decrease risk for VILI and promote lung recovery for those supported with ECMO.
Poly-ADP ribose polymerase inhibitor and androgen receptor signaling inhibitor for all comers for first-line treatment of metastatic castration-resistant prostate cancer: is gene sequencing out?
Authors: Higano Celestia S. , Cheng Heather H. 
Published: July 2023

Purpose of review
The landscape for first-line therapy (1L) of metastatic castration-resistant prostate cancer (mCRPC) is rapidly shifting. In the past 2 years, three phase 3 trials have examined the addition of a poly-ADP ribose polymerase inhibitor (PARPi) to an androgen receptor-signaling inhibitor (ARSI) in 1L. The FDA and the EMA recently considered whether one of these combinations should be approved for “all comers.” Here, we review the trial designs, assays for homologous recombination repair mutations (HRRm) and BRCA mutations (BRCAm), and predictive capacity of mutational status on treatment efficacy to understand the basis for the FDA decision.

Recent findings
The phase 3 trials, PROpel, MAGNITUDE, and TALAPRO-2, each compared PARPi and ARSI to placebo (PBO) plus ARSI. PROpel and TALAPRO-2 (cohort 1) included all comers (i.e., no prospective biomarker selection), while MAGNITUDE prospectively assigned patients to HRRm and HRR nonmutated cohorts and TALAPRO-2 (cohort 2) included only those with HRRm. Radiographic progression-free survival (rPFS) was the primary endpoint, and overall survival (OS) was a key secondary endpoint in all trials. Although rPFS with a PARPi and ARSI was improved versus PBO with ARSI, major conclusions differed.

Summary
The nuances and interpretation of these trials provide an understanding of the rationale for the FDA's decision to restrict the approval of olaparib and abiraterone and prednisone (AAP) as 1L therapy to those with biomarker evidence of BRCAm.
Pediatric Drug-Associated Pancreatitis Reveals Concomitant Risk Factors and Poor Reliability of Causality Scoring: Report From INSPPIRE
Authors: Morinville Veronique D. , Husain Sohail Z. , Wang Fuchenchu , Cress Gretchen A. , Abu-El-Haija Maisam , Chugh Ankur , Downs Elissa , Ellery Kate , Fishman Douglas S. , Freeman Alvin Jay , Gariepy Cheryl E. , Giefer Matthew , Gonska Tanja , Liu Quin , Maqbool Asim , Mark Jacob , Mcferron Brian Arthur , Mehta Megha , Nathan Jaimie D. , Ng Ken , Ooi Chee Y. , Perito Emily , Ruan Wenly , Schwarzenberg Sarah Jane , Sellers Zachary M. , Serrano Jose , Troendle David M. , Wilschanski Michael , Zheng Yuhua , Yuan Ying , Lowe Mark , Uc Aliye ,   on behalf of the Consortium for the Study of Chronic Pancreatitis, Diabetes and Pancreatic Cancer (CPDPC)
Published: July 2023

Objectives:
Drug-associated acute pancreatitis (DAP) studies typically focus on single acute pancreatitis (AP) cases. We aimed to analyze the (1) characteristics, (2) co-risk factors, and (3) reliability of the Naranjo scoring system for DAP using INSPPIRE-2 (the INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2) cohort study of acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) in children.

Methods:
Data were obtained from ARP group with ≥1 episode of DAP and CP group with medication exposure ± DAP. Physicians could report multiple risk factors. Pancreatitis associated with Medication (Med) (ARP+CP) was compared to Non-Medication cases, and ARP-Med vs CP-Med groups. Naranjo score was calculated for each DAP episode.

Results:
Of 726 children, 392 had ARP and 334 had CP; 51 children (39 ARP and 12 CP) had ≥1 AP associated with a medication; 61% had ≥1 AP without concurrent medication exposure. The Med group had other risk factors present (where tested): 10 of 35 (28.6%) genetic, 1 of 48 (2.1%) autoimmune pancreatitis, 13 of 51 (25.5%) immune-mediated conditions, 11 of 50 (22.0%) obstructive/anatomic, and 28 of 51 (54.9%) systemic risk factors. In Med group, 24 of 51 (47%) had involvement of >1 medication, simultaneously or over different AP episodes. There were 20 ARP and 4 CP cases in “probable” category and 19 ARP and 7 CP in “possible” category by Naranjo scores.

Conclusions:
Medications were involved in 51 of 726 (7%) of ARP or CP patients in INSPPIRE-2 cohort; other pancreatitis risk factors were present in most, suggesting a potential additive role of different risks. The Naranjo scoring system failed to identify any cases as “definitive,” raising questions about its reliability for DAP.
Myopia Progression in Adults: A Retrospective Analysis
Authors: Khan Hashim Ali , Naduvilath Thomas , Tahhan Nina , Sankaridurg Padmaja R. 
Published: July 2023

SIGNIFICANCE
Studies on adult myopia progression are limited. This retrospective analysis of a large data set of young adult myopes characterizes myopia progression during adulthood.

PURPOSE
This study aimed to determine the mean annual progression of myopia and to estimate the proportion of progressors in adult myopes.

METHODS
Longitudinal, noncycloplegic subjective refraction data for young adult myopes (spherical equivalent refractive error, −0.5 D or more), age ranging from 18 to 30 years, were retrospectively analyzed. The mean annual progression, as well as the proportion of progressors (at least −0.50 D shift between visits and annualized progression of −0.25 D or more), was estimated.

RESULTS
A total of 354 myopes (230 females [64.7%]), with a mean (standard deviation) age of 22.2 (3.8) years, were considered. The mean (standard deviation) annualized progression was −0.10 (0.21), −0.08 (0.2), and −0.04 (0.21) D in the 18- to 21-year, 22- to 26-year, and 27- to 30-year age groups, respectively (P = .003). The difference between 18- to 21- and 27- to 30-year age groups was significant (P = .05), whereas all other pairwise comparisons were not significant. The proportion (95% confidence interval) of progressors in the 18- to 21-, >21- to 26-, and >26- to 30-year age groups was 18.3% (14.9 to 21.7%), 10.9% (7.1 to 14.7%), and 8.8% (4.4 to 13.1%), respectively. The proportion of progressors working or studying in a higher learning/academic environment was 16.2% with an odds ratio (95% confidence interval) for progression of 2.07 (1.15 to 3.74) compared with those in nonacademic environments (P = .02), with no significant effect of sex or ethnicity.

CONCLUSIONS
This study is consistent with other studies on myopia in young adults, which show that myopia does not progress by substantial amounts throughout the adult years, particularly after the age of 21 years. Although future studies may be challenged by the small rates of change and the small proportion of progressors, further research is needed to understand the implications of adult myopia progression on clinical management.
Socket-residuum coupling integrity affects perception of external stimuli: Effects of altering the transtibial interface using vacuum-assisted suspension
Authors: Kent Jenny A. , Carnahan Kristin J. , Major Matthew J. 
Published: July 2023

Background:
Relative movement between the socket and residual limb can impair function in prosthesis users. It is plausible that, in addition to its mechanical effect, the integrity of the socket-residuum interface influences the ability of an individual to sense tactile cues through the prosthesis. Vacuum-assisted suspension (VAS) has been shown to reduce relative movement at this interface, providing a means to test this premise. The purpose of this pilot study was to assess the effects of altering socket-residuum interface integrity through the VAS pressure level on the thresholds of perception of an externally applied vibration stimulus.

Methods:
Seven unilateral transtibial prosthesis users participated. Socket-residual limb integrity was altered using the VAS subatmospheric (vacuum) pressure level. Vibration perception tests were conducted at low, mid, and high vacuum levels, targeting 0, 8, and 19 in Hg respectively, and performed in partially loaded and fully loaded conditions. Vibration intensity was increased using a dial until participants delivered a verbal signal indicating it was perceptible, and the nominal intensity was recorded.

Results:
Intensity thresholds decreased (ie, sensitivity increased) from low to high vacuum settings when fully loaded (P = 0.008). Differences when partially loaded were nonsignificant and variable across participants.

Conclusion:
This study provides preliminary evidence that altering the integrity between the socket and residual limb by modifying the vacuum level affects sensation related to the external environment experienced through the prosthesis, although translation of these findings to real-world stimuli remains to be tested.
Routine End-ischemic Hypothermic Oxygenated Machine Perfusion in Liver Transplantation from Donors After Brain Death
Authors: Grąt Michał , Morawski Marcin , Zhylko Andriy , Rykowski Paweł , Krasnodębski Maciej , Wyporski Anya , Borkowski Jan , Lewandowski Zbigniew , Kobryń Konrad , Stankiewicz Rafał , Stypułkowski Jan , Hołówko Wacław , Patkowski Waldemar , Mielczarek-Puta Magdalena , Struga Marta , Szczepankiewicz Benedykt , Górnicka Barbara , Krawczyk Marek 
Published: July 2023

Objective:
To assess whether end-ischemic hypothermic oxygenated machine perfusion (HOPE) is superior to static cold storage (SCS) in preserving livers procured from donors after brain death (DBD).

Summary Background Data:
There is increasing evidence of the benefits of HOPE in liver transplantation, but predominantly in the setting of high-risk donors.

Methods:
In this randomized clinical trial, livers procured from DBDs were randomly assigned to either end-ischemic dual HOPE for at least 2 h or SCS ( 1:3 allocation ratio). The Model for Early Allograft Function (MEAF) was the primary outcome measure. The secondary outcome measure was 90-day morbidity. (ClinicalTrials. gov, NCT04812054).

Results:
Of the 104 liver transplantations included in the study, 26 were assigned to HOPE and 78 to SCS. Mean MEAF was 4.94 and 5.49 in the HOPE and SCS group (P=0.24), respectively, with the corresponding rates of MEAF >8 of 3.8% (1/26) and 15.4% (12/78; P=0.18). Median comprehensive complication index was 20.9 after transplantations with HOPE and 21.8 after transplantations with SCS (P=0.19). Transaminases activity, bilirubin concentration, and international normalized ratio were similar in both the groups. In the case of donor risk index >1.70, HOPE was associated with significantly lower mean MEAF (4.92 vs. 6.31; P=0.037) and lower median comprehensive complication index (4.35 vs. 22.6; P=0.050). No significant differences between HOPE and SCS were observed for lower donor risk index values.

Conclusion:
Routine use of HOPE in DBD liver transplantations does not seem justified as the clinical benefits are limited to high-risk donors.
Loss of appetite in patients with cancer: an update on characterization, mechanisms, and palliative therapeutics
Authors: Haemmerle Robert J. , Jatoi Aminah 
Published: July 2023

Purpose of review
Over the past year, loss of appetite in patients with cancer has continued to be an area of active investigation. This review provides an update of recently published findings.

Recent findings
Despite the emergence of new cancer therapeutic agents, this symptom of loss of appetite continues to trouble patients, and it continues to be associated with poor survival. Recent preclinical research promises to lead to newer approaches and newer, more effective palliative agents. Recent clinical research shows that agents such as olanzapine, anamorelin, and cannabis either do or might palliate this symptom.

Summary
Loss of appetite in patients with cancer remains an important area of clinical and research focus. Recent published data provide greater clarity with respect to how to palliate this symptom. Today, although clinicians have more options to palliate cancer-associated loss of appetite than ever before, questions remain unanswered about how to palliate this symptom optimally and how to improve the quality of life of patients who suffer from it.
Proteomic studies of human placentas reveal partnerships associated with preeclampsia, diabetes, gravidity, and labor
Authors: Ho Shannon J. , Chaput Dale , Sinkey Rachel G. , Garces Amanda H. , New Erika P. , Okuka Maja , Sang Peng , Arlier Sefa , Semerci Nihan , Steffensen Thora S. , Rutherford Thomas J. , Alsina Angel E. , Cai Jianfeng , Anderson Matthew L. , Magness Ronald R. , Uversky Vladimir N. , Cummings Derek A. T. , Tsibris John C. M. 
Published: July 2023

AbstractVEGFR2 is a central regulator of placental angiogenesis. The study of the VEGFR2 proteome of chorionic villi at term revealed its partners MDMX and PICALM. The oxytocin receptor (OT-R) and vasopressin V1aR receptor were detected in MDMX and PICALM immunoprecipitations. Immunogold electron microscopy showed VEGFR2 on endothelial cell (EC) nuclei, mitochondria, and Hofbauer cells (HC), the tissue-resident macrophages. MDMX, PICALM, and V1aR were on EC plasma membranes, nuclei, and HC nuclei. Unexpectedly, PICALM and OT-R were detected on EC projections into the fetal lumen and OT-R on 20-150 nm clusters therein, prompting the hypothesis that placental exosomes transport OT-R to the fetus and across the blood-brain barrier. Insights on gestational complications were gained by univariable and multivariable regression analyses associating preeclampsia with lower MDMX protein levels in membrane extracts of chorionic villi, and lower MDMX, PICALM, OT-R, and V1aR with spontaneous vaginal deliveries compared to cesarean deliveries before labor. We found select associations between higher MDMX, PICALM, OT-R and either gravidity, diabetes, BMI, maternal age, or neonatal weight, and correlations between PICALM-OT-R (p<2.7x10-8), PICALM-V1aR (p<0.006), and OT-R-V1aR (p<0.001). These results offer for exploration new partnerships in metabolic networks, tissue-resident immunity, and labor, notably for HC that predominantly express MDMX.
Machine learning fairness analysis on clinical data of The EMory BrEast imaging Dataset (EMBED)
Authors: Ramachandra Vikas , Sethi Mohit 
Published: July 2023

AbstractThis paper explores the use of machine learning (ML) for predictive modeling on clinical data from the EMory BrEast imaging Dataset (EMBED) [1] with a focus on ML model fairness analysis. The aim of this study is to develop and evaluate fair machine learning models that can accurately predict breast cancer risk. We trained and tested various machine-learning models. Our findings show that machine learning can be effective for predicting breast cancer risk or diagnosing breast cancer, and that fairness considerations are crucial in the development of such models. Overall, our study highlights the potential of machine learning for clinical applications while emphasizing the need for ethical and fair practices in this field.
Parental intention, attitudes, beliefs, trust and deliberation towards childhood vaccination in the Netherlands in 2022: Indications of change compared to 2013
Authors: Knijff Marthe , van Lier Alies , Boer Maartje , de Vries Marion , Hament Jeanne-Marie , de Melker Hester E. 
Published: July 2023

AbstractBackground and aimVaccine uptake within the Dutch National Immunisation Programme (NIP) has slightly declined since the COVID-19 pandemic. We studied psychosocial factors of vaccine uptake, namely parental intention, attitudes, beliefs, trust and deliberation (i.e., self-evidence), before (2013) and two years into the pandemic (2022).MethodsIn 2022 and 2013, parents with a young child (aged <3.5 years) participated in online surveys on vaccination (n=1,000 and 800, (estimated) response=12.2% and 37.2%, respectively). Psychosocial factors were measured on 7-point Likert scales. Multivariate logistic regression analysis was used to study differences between parents in 2022 and 2013 in ‘negative’ scores (≤2) of psychosocial factors.ResultsIn both 2022 and 2013, most parents with a young child expressed positive intention (2022=83.1%, 2013=87.0%), attitudes (3 items: 2022=66.7%-70.9%, 2013=62.1%-69.8%) and trust (2022=51.8%, 2013=52.0%) towards the NIP and felt that vaccinating their child was self-evident (2022=57.2%, 2013=67.3%). Compared to parents with a young child in 2013, parents with a young child in 2022 had significantly higher odds of reporting negative attitudes towards vaccination (3 items combined: OR=2.84), believing that vaccinations offer insufficient protection (OR=4.89), that the NIP is not beneficial for the protection of their child’s health (OR=2.23), that vaccinating their child does not necessarily protect the health of other children (OR=2.24) or adults (OR=2.22) and that vaccinations could cause severe side effects (OR=2.20), preferring natural infection over vaccination (OR=3.18) and reporting low trust towards the NIP (OR=1.73).ConclusionsAlthough most parents had positive intention, attitudes and trust towards vaccination and perceived vaccinating their child as self-evident, proportions of parents with negative scores were slightly larger in 2022 compared to 2013. Monitoring these determinants of vaccine uptake and developing appropriate interventions could contribute to sustaining high vaccine uptake.
New frontiers in health literacy: Using ChatGPT to simplify health information for people in the community
Authors: Ayre Julie , Mac Olivia , McCaffery Kirsten , McKay Brad R , Liu Mingyi , Shi Yi , Rezwan Atria , Dunn Adam G 
Published: July 2023

AbstractBackgroundMost health information does not meet the health literacy needs of our communities. Writing health information in plain language is time-consuming but the release of tools like ChatGPT may make it easier to produce reliable plain language health information.ObjectiveTo investigate the capacity for ChatGPT to produce plain language versions of health texts.DesignObservational study.SubjectsTwenty-six health texts from reputable websites.InterventionsChatGPT was prompted to ‘rewrite the text for people with low literacy.’ Researchers captured three revised versions of each original text.Main MeasuresObjective health literacy assessment, including Simple Measure of Gobbledygook (SMOG), proportion of the text that contains complex language (%), number of instances of passive voice, and subjective ratings of key messages retained (%).Key ResultsOn average, original texts were written at Grade 12.8 (SD=2.2) and revised to Grade 11.0 (SD=1.2), p<0.001. Original texts were on average 22.8% complex (SD=7.5%) compared to 14.4% (SD=5.6%) in revised texts. Original texts had on average 4.7 instances (SD=3.2) of passive text compared to 1.7 (SD=1.2) in revised texts. On average 80% of key messages were retained. The more complex original texts showed more improvements than less complex original texts. For example, when original texts were ≥ Grade 13, revised versions improved by an average 3.3 Grades (SD=2.2), p<0.001. Simpler original texts (< Grade 11) improved by an average 0.5 grades (SD=1.4), p<0.001.ConclusionsThis study used multiple objective assessments of health literacy to demonstrate that ChatGPT can simplify health information while retaining most key messages. However, the revised texts typically did not meet health literacy targets for grade reading level, and improvements were marginal for texts that were already relatively simple.