bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of repeat testing in tuberculosis patients with a trace call on Xpert MTB/RIF Ultra: a retrospective cohort study
Authors: Jha Suyash , Gupta Nitin , Kumar Tirlangi Praveen , Chawla Kiran , Shenoy Vishnu P , Varma Muralidhar , Manu Mohan K
Published: January 2025

Background

This study aimed to see if rifampicin susceptibility can be determined on repeat sampling in pulmonary tuberculosis with a trace call on the first GeneXpert Ultra report.

Methods

This retrospective cohort study included adults with a GeneXpert Ultra trace call in the first respiratory sample from January 2021 to June 2024.

Results

Of the 27 patients with repeat sampling done after the initial trace call, rifampicin susceptibility could be determined in 37% (n=10) of patients.

Conclusions

Repeating GeneXpert Ultra testing in patients with an initial trace call is valuable for determining rifampicin susceptibility.
Polyunsaturated fatty acids suppress PIEZO ion channel mechanotransduction in articular chondrocytes
Authors: Marushack Gabrielle K. , Savadipour Alireza , Tang Ruhang , Garcia‐Castorena Jaquelin M. , Rashidi Neda , Nims Robert J. , Harasymowicz Natalia S. , Kim Yu Seon , Guilak Farshid
Published: January 2025

Osteoarthritis (OA) is characterized by articular cartilage degeneration, leading to pain and loss of joint function. Recent studies have demonstrated that omega‐3 (ω3) polyunsaturated fatty acid (PUFA) supplementation can decrease injury‐induced OA progression in mice fed a high‐fat diet. Furthermore, PUFAs have been shown to influence the mechanical properties of chondrocyte membranes, suggesting that alterations in mechanosensitive ion channel signaling could contribute to the mechanism by which ω3 PUFAs decreased OA pathogenesis. Here, we hypothesized that PUFAs may alter mechanical signaling through PIEZO1 (activated by changes in membrane tension) and TRPV4 (activated by physiologic mechano‐osmotic signals), as these mechanosensitive cation channels have been shown to influence OA progression. Our results demonstrated that PUFAs reduced chondrocyte sensitivity to single‐cell mechanical compression and to pharmacologic agonists of PIEZO1 and TRPV4, with ω3 PUFAs having the most significant effects overall. We also found that supplementation with ω6 PUFA linoleic acid (LA) altered the biophysical properties of chondrocytes, as evidenced by increased intracellular lipid droplet formation and more rapid membrane rupture in response to hypo‐osmotic shock, suggesting that LA increases chondrocyte membrane susceptibility to damage. Our findings underscore the differential impacts of specific PUFAs on chondrocyte signaling and membrane properties and provide important considerations in the development of nutritional interventions to prevent or treat OA.
Undernutrition affects metabolism and immune response in subcutaneous adipose tissue of pregnant ewes
Authors: Li Baoyuan , Wu Weibin , Lu Huizhen , Liu Shuai , Si Xiongyuan , Bai Binqiang , Cheng Jianbo , Ding Xiaoling , Mao Shengyong , Xue Yanfeng
Published: January 2025

Pregnant ewes mobilize body fat to increase energy supply for fetal growth and development upon undernutrition, which disrupts the metabolic homeostasis of the body. However, the comprehensive metabolic changes in subcutaneous adipose tissue upon undernutrition are poorly understood. In this study, an undernutrition sheep model was established to investigate the effects of undernutrition on metabolic changes, immune response, and inflammation in subcutaneous fat through transcriptome, RT‐qPCR, and metabolome analysis. Results showed that undernutrition changed the total transcriptional and metabolic profiles of adipose tissue. Compared to the controls, differentially expressed genes (DEGs) involved in fatty acid synthesis, triglyceride genesis, and lipid transport were downregulated in undernourished ewes, while DEGs related to fatty acid and triglyceride degradation were upregulated. Almost all lipid‐related differential metabolites (DMs) were downregulated. DEGs and DMs involved in glucose metabolism and glycogen degradation were downregulated, while glycogen synthesis and carbohydrate transport were upregulated. DEGs linked to amino acid degradation were upregulated and some amino acids and derivatives were downregulated. KEGG pathway analysis showed complement and coagulation cascades were enriched significantly by DEGs, and DEGs related to coagulation, macrophage, and inflammation were upregulated while DEGs associated with the complement system were downregulated. Undernutrition during late gestation disrupted the metabolism of lipids, carbohydrates, and amino acids in adipose tissue, which weakened the complement system and immune response and may have ultimately led to inflammation.
Multiple myeloma–associated non‐crystalline proximal tubulopathy and crystalline cast nephropathy: Biochemical and structural features of disease‐causing monoclonal kappa light chains
Authors: Ezawa Toshinori , Otomo Riku , Kariya Yumi , Nozawa Kyoko , Kyoya Sonosuke , Furutani Chikako , Noguchi Keiichi , Yohda Masafumi , Odaka Masafumi , Matsumura Hirotoshi , Saito Ayano , Saito Masaya , Abe Fumito , Fujioka Yuki , Kitadate Akihiro , Wakui Hideki , Takahashi Naoto
Published: January 2025

Various tubular diseases in patients with multiple myeloma (MM) are caused by monoclonal immunoglobulin light chains (LCs). However, the physicochemical characteristics of the disease‐causing LCs contributing to the onset of MM‐associated tubular diseases remain unclear. We herein report a rare case of MM‐associated combined tubulopathies: non‐crystalline light chain proximal tubulopathy (LCPT) and crystalline light chain cast nephropathy (LCCN). The patient's urinary κ‐LC (Bence–Jones proteins, BJP‐κ PT‐CN) was detected through immunofixation. Renal biopsy revealed cytoplasmic vacuoles in swollen proximal tubular cells and distal tubular casts. Immunohistochemistry showed proximal tubular reabsorption granules and distal tubular casts positively stained with an anti‐κ‐LC antibody. Electron microscopy identified vacuolation and an increased number of lysosomes in proximal tubular epithelial cells without crystalline structures. Distal tubular casts comprised numerous crystals with both rod‐shaped and needle‐like configurations and tube‐shaped materials. To elucidate the molecular mechanisms underlying tubular toxicity, we performed the following physicochemical analyses of BJP‐κ PT‐CN: N‐terminal amino acid sequencing, cDNA cloning, size‐exclusion chromatography, thermal shift assays, and X‐ray crystallography. The variable segment of BJP‐κ PT‐CN was derived from the IGKV1‐39 gene. The characteristic features of BJP‐κ PT‐CN were a positively charged surface patch, concentration‐dependent monomer‐dimer equilibrium, and the R61G mutation. This is the first biochemical and structural characterization of disease‐causing BJPs in MM‐associated LCPT and crystalline LCCN. The results obtained suggest that these characteristic features enhance protein binding to negatively charged sites on brush‐border membranes in proximal tubules and promote the formation of organized casts in distal tubular lumens.
The histone demethylase KDM6B links obstructive sleep apnea to idiopathic pulmonary fibrosis
Authors: Han Shuangyu , Huang Jie , Yang Changqing , Feng Jing , Wang Yubao
Published: January 2025

Obstructive sleep apnea (OSA) is increasingly recognized for its link to idiopathic pulmonary fibrosis (IPF), though the underlying mechanisms remain poorly understood. Histone lysine demethylase 6B (KDM6B) may either prevent or promote organ fibrosis, but its specific role in IPF is yet to be clarified. This study aimed to investigate the function and mechanisms of KDM6B in IPF and the exacerbating effects of OSA. We assessed KDM6B levels in lung tissues from IPF patients, IPF mouse models, and a dual‐hit model combining OSA‐associated intermittent hypoxia (IH) with bleomycin (BLM) or TGF‐β1. We evaluated pulmonary fibrosis, myofibroblast activation, and oxidative stress. KDM6B levels were elevated in lung tissues from IPF patients and BLM‐treated mice, as well as in TGF‐β1‐stimulated myofibroblasts. Importantly, IH significantly worsened BLM‐induced pulmonary fibrosis and TGF‐β1‐induced myofibroblast activation, further amplifying KDM6B expression both in vivo and in vitro. Inhibition of KDM6B reduced pulmonary fibrosis and decreased fibroblast activation and migration in IPF and dual‐hit models. Mechanistically, KDM6B inhibition led to decreased NOX4 expression and reduced oxidative stress. KDM6B plays a critical role in promoting pulmonary fibrosis and mediating the exacerbating effects of OSA on this condition. Our findings identify KDM6B as a novel potential therapeutic target for IPF.
Budget Impact Analysis of Integrative Medicine Practices for Pediatric Patients With Chronic Pain
Authors: Gong Cynthia L. , Okoro Chelsea C. , Wan Ruihan , Lopez Cristal , Ngo Nhat H. , Gold Jeffrey I.
Published: January 2025

Objectives:

Chronic pain is a leading cause of morbidity in children and adolescents globally but can be managed with a combination of traditional Western medicine and integrative medicine (IM) practices. This combination has improved various critical health outcomes, such as quality of life, sleep, pain, anxiety, and health care utilization. These IM practices include acupuncture, yoga, biofeedback, massage, mindfulness, or any combination of these modalities. The current article﻿ developed a budget impact model to estimate the institutional costs of implementing these practices among adolescents.

Methods:

A decision tree was used to estimate the reduction in hospitalizations and emergency department (ED) use based on a previously published retrospective analysis of children receiving IM practices comparing utilization rates 1-year pre-implementation and post-implementation of IM services (Figure 1). Costs associated with implementing each modality were based on hourly compensation rates for licensed professionals administering each service and equipment associated with delivery (eg, acupuncture needles, biofeedback equipment, and sensors). The cost of each hospitalization and ED visit was derived from the literature. In addition, cost savings were estimated based on government-contracted and commercial-contracted reimbursement rates for each service.

Results:

Cost savings were approximated to range from $1344 to $3439 per patient, with even greater cost savings of up to $6000 and $4132 when accounting for governmental and commercial payer reimbursement, respectively.

Discussion:

IM leads to improved pain relief when combined with traditional medicine and yields significant cost savings, thus supporting the routine implementation of IM alongside traditional medicine in health care settings.
Protein alterations in patients with delirium after cardiac surgery: An exploratory case-control sub-study of the VISION Cardiac Surgery Biobank
Authors: Spence Jessica , Devereaux PJ , Bashir Shaheena , Brady Katheryn , Sun Tao , Chan Matthew T.V. , Wang Chew Yin , Lamy Andre , Whitlock Richard P. , McIntyre William F. , Belley-Côté Emilie , Paré Guillaume , Chong Michael
Published: January 2025

Background:

Delirium is an acute state of confusion associated with adverse postoperative outcomes. Delirium is diagnosed clinically using screening tools; most cases go undetected. Identifying a delirium biomarker would allow for accurate diagnosis, application of therapies, and insight into causal pathways. To agnostically discover novel biomarkers of delirium, we conducted a case-control sub-study using the VISION-Cardiac Surgery biobank. Our objective was to identify candidate biomarkers to investigate in future studies.

Methods:

We obtained a convenience sample of 30 patients with delirium on postoperative day 1 matched to 30 matched controls by age, sex, ethnicity, center and cardiopulmonary bypass time. The Olink Explore 3K platform was used to identify blood protein alterations on postoperative day 3. Protein concentrations were expressed as normalized protein expression (NPx) units (log2 fold scale). We compared protein expression between cases and controls using a paired t-test and reported significantly different biomarkers based on a False Discovery Rate (FDR)-adjusted p-value<0.05.

Results:

Of 2,865 unique serum proteins, 26 (0.9%) were significantly associated with delirium status; all were elevated in cases versus controls at an FDR<0.05. Pathway analysis identified “calcium-release channel activity” (Padj=0.02) and “Guanosine 5’ triphosphate (GTP)-binding” (Padj=0.005) functions as characteristic of proteins associated with delirium. The top three differentially expressed biomarkers were FKBP1B (Padj=0.003), C2CD2L (Padj=0.004), and RAB6B (Padj=0.004). The inflammatory biomarker IL-8 (CXCL8) (mean difference = 2.36; P=3.6x10-4) was also associated with delirium.

Discussion:

We identified 26 biomarkers significantly associated with delirium; all are novel except for IL-8. We did not identify an association between delirium and recognized neuro-inflammatory proteins and markers of brain injury, which supports using biomarkers to differentiate between delirium and other neurological conditions. While exploratory, our findings support using biomarkers to diagnose postoperative delirium and validate using agnostic screens to identify potential delirium biomarkers.
A New Way Forward for Women's Health Research at the National Institutes of Health
Authors: Debbink Michelle P. , Tuuli Methodius G. , Geller Amy , Salganicoff Alina N. , Burke Sheila P. , Secord Angeles Alvarez
Published: January 2025

Despite efforts to address inequities, research on women's health conditions (defined as those that uniquely or differently affect women and female individuals) remain significantly understudied. As directed by Congress, the National Institutes of Health (NIH) Office of Research on Women's Health requested the National Academies of Sciences, Engineering, and Medicine (National Academies) to conduct an assessment of the state of women's health research at the NIH. The findings of the National Academies committee include: 1) a significant funding inequity, with less than 8% of the total NIH grant budget for fiscal year 2023 allocated to women's health research; 2) a need for improved strategic NIH-wide priority setting, oversight, and adherence to existing policies to support women's health research; 3) a need for a specific institute for research on conditions specific to women's health; and 4) a need for sufficient training and additional funding to grow and retain the women's health research workforce. The National Academies committee recommends restructuring women's health research at the NIH by creating a new Women's Health Research Institute and cross-disciplinary Women's Health Research Fund, including greater accountability and an infusion of new funds to support both research and career development in women's health. The combination of the new institute, greater prioritization and accountability, and new funding would lead to more rapid innovations and advancements, with the ultimate goal of improving women's health and well-being, which, in turn, improves the well-being of families and communities and bolsters a vibrant, healthier society.
Research on the mechanism of eugenol in the treatment of liver cancer based on network pharmacology, molecular docking technology, and in vitro experiments
Authors: Liu Kaiping , Jiang Jiuliang , Yu Zhenyu , Wang Yunhao , Wang Min , Zhu Haitao
Published: January 2025

Eugenol, a phenolic natural product with diverse pharmacological activities, remains unexplored in liver cancer. Using network pharmacology, we investigated eugenol’s therapeutic mechanisms in liver cancer. We obtained eugenol’s molecular structure from PubChem and screened its targets using similarity ensemble approach in Swiss Target Predictiondatabases. Overlapping genes with liver cancer-related genes from GeneCards were identified. Protein–protein interaction networks, Gene Ontology annotations, and Kyoto Encyclopedia of Genes and Genomes pathway analyses were conducted. A target-pathway network revealed eugenol’s interaction with 122 liver cancer-related genes. Molecular docking confirmed eugenol’s high affinity for mitochondrial nicotinamide adenine dinucleotide, reduced form (NADH) dehydrogenase 1 (MT-ND1), AKT1, NDUFB7, and NADH dehydrogenase (complex I) subunit S3 (NDUFS3). Expression levels of these targets in normal liver and liver cancer tissues were examined using GEPIA2 and HPA databases. The CCK-8 assay and colony formation assay demonstrated that eugenol significantly inhibited the proliferation of hepatocellular carcinoma cells. Western blot analysis confirmed that eugenol upregulated MT-ND1 while downregulating the expression of targets such as AKT1, NDUFB7, and NDUFS3. Furthermore, it was found that eugenol could influence the expression of the AKT1 target through the AKT/p70 S6K pathway. This study provides new insights into the potential mechanisms of eugenol in liver cancer and offers novel perspectives for network-based liver cancer research.
A scoping review and thematic analysis of the effects of tropical cyclones on diarrheal diseases
Authors: Lin Szu Yu , Chua Paul L. C. , Yuan Lei , Hossain Nasif , He Jinyu , Yamasaki Lisa , Madaniyazi Lina , Ng Chris Fook Sheng , Tobias Aurelio , Hashizume Masahiro
Published: January 2025

Background:

Tropical cyclones pose significant health risks and can trigger outbreaks of diarrheal diseases in affected populations. Although the effects of individual hazards, such as rainfall and flooding, on diarrheal diseases are well-documented, the complex multihazard nature of tropical cyclones is less thoroughly explored. To date, no dedicated review comprehensively examines the current evidence and research on the association between tropical cyclones and diarrheal diseases.

Methods:

We performed a scoping review to map the literature on tropical cyclones and diarrheal diseases. A comprehensive literature search was performed across multiple online databases, including PubMed/MEDLINE, Web of Science, Scopus, Google Scholar, and ProQuest. We then performed a thematic analysis on the specific transmission pathways between tropical cyclones and diarrheal diseases as described in the literature.

Results:

A total of 96 studies were included and categorized in this scoping review. Of these, 23 studies quantitatively assessed the association between tropical cyclones and diarrheal diseases, with more than half reporting a positive association. Additionally, we identified 30 studies that detailed transmission pathways, which we used for thematic analysis. Significant variability was observed in the definition of tropical cyclone exposure, with studies using different criteria such as an event, wind speed, or rainfall. Most studies used pre-post comparison designs without concurrent control groups, which can introduce limitations affecting internal validity by not accounting for temporal confounders. Diarrheal diseases can either increase or decrease during and after tropical cyclones, depending on the specific pathogens and the different strengths of tropical cyclones.

Conclusion:

The variability in exposure definitions and study designs impedes the ability to quantitatively pool evidence. To improve the comparability and reliability of future research, we recommend that studies explore how different tropical cyclone exposure definitions impact results to identify the most appropriate metrics. We also suggest adopting more robust study designs, such as difference-in-difference or controlled interrupted time series for studying single tropical cyclone events, and case-crossover designs for studying multiple events. Additionally, studies examining specific causal pathways, such as integrating environmental sampling with health outcomes, should be explored to identify effective prevention strategies.
Surgical and multimodal approaches to right-sided cardiac tumours
Authors: Patel Shubh K. , Dhingra Nitish K. , Cusimano Robert J.
Published: January 2025

Purpose of review

Cardiac tumours present significant clinical challenges due to their wide differential, complex anatomical and physiological implications, as well as the potential for widespread invasion in the case of malignancies. This review synthesizes recent findings surrounding the diagnosis and management of specifically right-sided cardiac tumours, with a particular focus on surgical resection and reconstructive techniques.

Recent findings

Management of cardiac tumours can be categorized into three key phases. First: early and accurate diagnosis is critical for improving outcomes, especially in malignancies. Advances in imaging modalities like MRI, CT, PET-CT, and biopsy techniques enhance diagnostic accuracy. Second: surgical resection is a cornerstone treatment for both benign and malignant right-sided cardiac tumours. Surgery is often curative for benign tumours, while for malignant tumours, R0 resection (complete microscopic removal) in appropriate candidates correlates with better survival. Third: managing cardiac malignancies necessitates a multidisciplinary approach, integrating additional therapies such as chemotherapy, radiation, and emerging immunotherapies tailored to patient and tumour characteristics.

Managing right-sided cardiac tumours demands interdisciplinary expertise. Standardized protocols are limited by the rarity of cases and insufficient high-quality data. International collaboration and sharing of experiences through prospective registries and clinical studies are essential to advancing knowledge and improving patient outcomes.
Role of preoperative biliary stents, bile contamination and antibiotic therapy in patients undergoing pancreaticoduodenectomy: A Retrospective Cohort Study
Authors: Fontani Giovanni , Nelli Tommaso , Canonico Giuseppe , Fratarcangeli Riccardo , Gabellini Linda , Damigella Andrea , Anastasi Alessandro
Published: January 2025

Background:

The use of preoperative biliary drainage before pancreaticoduodenectomy (PD) remains controversial. The correlation between antibiotic prophylaxis and intraoperative biliary swab is a matter of further investigation to reduce postsurgical complications.

Methods:

The operative series of PD performed at the Pancreatic Surgery reference center for the USL Toscana Centro between January 1, 2021 and August 2023 were retrospectively analyzed. This study compared stented and nonstented patients undergoing PD to assess any differences in postoperative morbidity and mortality. In addition, intraoperative bile and abdominal drain fluid cultures were microbiologically assessed, and the susceptibility of bacterial isolates to antibiotics currently used for preoperative short-term prophylaxis was evaluated.

Results:

Almost 47/90 underwent preoperative stenting, 30/47 had jaundice above 12 mg/dl and went to upfront surgery, and 12/47 underwent neoadjuvant chemotherapy. Biliary microbial cultures were positive in 38/90 patients, among them 28 showed a polymicrobial flora. The most frequent postoperative complications detected were: abdominal abscess 9/90, pancreatic fistula type B-C 8/90, and delayed gastric emptying 7/90. From the statistical analysis, a P value = 0.0215 was obtained for the correlation between the preoperative stent group and P = 0.0285 with positive bile culture.

Conclusion:

There is no statistically significant correlation between the result of rectal and biliary swabs and the development of postoperative complications. Instead, biliary stent placement and positive biliary culture examination are two statistically significant risk factors for the development of postoperative complications. In relation to the increased rate of complications in patients subjected to preoperative stenting, careful presurgical evaluation is necessary to define who will have to undergo this procedure.
SNHG16 alleviates pulmonary ischemia-reperfusion injury by promoting the Warburg effect through regulating MTCH2 expression: experimental studies
Authors: Zhou Wenyong , Wang Shaohua , Yang Jichun , Shi Qi , Feng Nana , Gao Kaiheng , Posum Wan , Shi Mengkun , Xiang Meng , Shi Meng
Published: January 2025

Background:

Pulmonary ischemia-reperfusion injury (PIRI) is a major cause of fatality post-lung transplantation. Though some long non-coding RNAs (lncRNAs) have been studied in acute lung injury (ALI), their effects on PIRI remain undefined. The present study aims to explore the underlying mechanism of small nucleolar RNA host gene 16 (SNHG16) in PIRI.

Methods:

PIR mouse and oxygen-glucose deprivation/reoxygenation (OGD/R) cell models were established. Exosomes were extracted from human pulmonary microvascular endothelial cells (HPMECs). Functional and rescue experiments were conducted in OGD/R-exposed HPMECs, OGD/R-exposed pulmonary alveolar epithelial type II cells (AECs), and I/R model mice. The relationships among SNHG16, miR-372-3p/miR-373-3p, and MTCH2 were also verified using dual luciferase reporter assay, RNA pull-down and RIP assay.

Results:

SNHG16 was downregulated in OGD/R-exposed HPMECs, and SNHG16 overexpression accelerated proliferation, angiogenesis, and ameliorated mitochondrial respiration in OGD/R-exposed HPMECs. HPMEC-derived exosomal SNHG16 suppressed OGD/R-induced type II AEC injury. SNHG16 ameliorated lung injury in PIR mice. Mechanistically, SNHG16 targeted and negatively regulated miR-372-3p and miR-373-3p expression, and MTCH2, a target gene of miR-372-3p/miR-373-3p. SNHG16 was found to upregulate MTCH2 expression not only in a miR-372-3p and miR-373-3p-dependent manner but also suppress ubiquitination induced MTCH2 degradation.

Conclusions:

Our findings revealed that SNHG16 overexpression suppressed OGD/R-induced HPMEC apoptosis by promoting Warburg effect, and HPMEC-derived exosomal SNHG16 alleviated PIRI through the miR-372-3p/miR-373-3p/MTCH2 axis, suggesting that SNHG16 as a therapeutic target for PIRI.
The impact of deep response to ursodeoxycholic acid in primary biliary cholangitis – should it be the new clinical standard?
Authors: Martins Adrielly , Levy Cynthia
Published: January 2025

Purpose of review

This review explores the emerging concept of “deep response” in primary biliary cholangitis (PBC), defined by the normalization of biochemical markers, particularly alkaline phosphatase and bilirubin. It examines its potential as a new standard for disease management and its implications for long-term patient outcomes, health policies, and clinical decision-making.

Recent findings

Recent studies suggest that achieving a deep response significantly improves long-term outcomes in some patients with PBC. In particular, a significant complication-free survival gain was observed among patients who at baseline were at high risk for disease progression. However, limitations in data and the variability in patient populations pose challenges for universal adoption of this standard.

Deep biochemical response represents a promising new standard for optimizing PBC management, offering measurable goals for clinicians and potentially improved long-term outcomes for patients. However, further research is necessary to better define the appropriate biochemical thresholds, understand the risks of overprescribing, and identify patient subgroups that are most likely to benefit from this strategy. A balanced, patient-centered approach incorporating deep response into comprehensive management could improve care for high-risk PBC patients.
Using Implementation Science to Assess Barriers to Agreement on Sedation Goal Setting and Assessment
Authors: Yang Youyang , Becla Kate , Kennedy Heather , Eder Katrina , Akhondi-Asl Alireza , Mehta Nilesh M. , Geva Alon
Published: January 2025

OBJECTIVES:

Sedation assessment and goal setting using a validated assessment tool are key components of the ICU Liberation bundle. Appropriate integration of these bundle elements into daily practice remains challenging. Understanding barriers is an important step toward implementation of these best practice bundle elements.

DESIGN:

Two-phased explanatory mixed methods assessment carried out 2022–2023.

SETTING:

Forty-bed quaternary PICU.

SUBJECTS:

Bedside nurses and prescribers caring for mechanically ventilated patients on sedative infusions.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Forty-one nurses and 32 prescribers participated in the phase 1 pre-education assessments (2022). We identified lack of correlation between the providers’ stated State Behavioral Scale (SBS) numerical goal and descriptive goal and hypothesized that this discrepancy was either due to a knowledge gap or disagreement on sedation goals. To investigate this hypothesis, we performed a phase 2 assessment (2022–2023), starting with a multipronged educational activity, followed by a repeat survey that included a qualitative interview. One hundred ninety nurses and 45 prescribers received the educational activity. Twenty-eight nurses and 22 prescribers participated in the phase 2 assessments with the qualitative interview. Although correlation of the sedation goal between providers improved, it remained poor. Subsequent qualitative interview data indicated that the reasons for persistent disagreement in the sedation goal for a given patient were related to individual providers’ beliefs and attitudes toward sedation, rather than lack of understanding about using the SBS to set a target sedation goal.

CONCLUSIONS:

Barriers to setting and managing daily patient sedation goal in the PICU extend beyond providers’ knowledge gaps. An improved understanding of underlying barriers is essential for successful implementation of evidence-based sedation guidelines.
Impact of Social Determinants of Health on Pre-exposure Prophylaxis Care for HIV Prevention
Authors: Chan Philip A. , Goedel William C. , Li Yu , Mena Leandro , Patel Rupa R. , Marshall Brandon D. L. , Yelena Malyuta , Ward Lori , Underwood Ashley , Johnson Catrell J. , Gomillia Courtney E. , Almonte Alexi , Tao Jun , Curoe Kate , Villalobos Jesus , Nunn Amy S.
Published: January 2025

Background:

HIV continues to disproportionately impact men who have sex with men (MSM) in the United States (US). Pre-exposure prophylaxis (PrEP) is effective, but disparities persist. Limited studies have conducted systematic evaluations of social determinants of health (SDOH) and their effects on PrEP persistence among MSM.

Setting:

We enrolled MSM into a prospective observational cohort to assess progression through the PrEP care continuum. We enrolled patients from three diverse US settings from 2018-2022.

Methods:

We explored the impact of SDOH on PrEP persistence (defined as successfully obtaining PrEP prescriptions and/or clinical documentation of retention in PrEP care) at 6- and 12-months using multilevel, mixed-effects logistic models.

Results:

A total of N=300 MSM were enrolled. Median age was 28 years; 40% were Black/African American (B/AA), and 11% were Hispanic/Latino (H/L). PrEP persistence was 84.7% and 49.3% at 6- and 12-months, respectively. In the unadjusted analysis, B/AA and H/L individuals were 56% and 54%, respectively, less likely to demonstrate PrEP persistence at 6- and 12-months compared to white/non-H/L individuals. Findings were no longer significant after adjusting for economic stability and educational attainment. Individuals with higher levels of internalized homophobia were less likely to persist on PrEP. Every 1-unit increase on a validated measure of internalized homophobia was independently and negatively associated with PrEP persistence (adjusted odds ratio = 0.95, 95% CI: 0.93-0.98).

Conclusion:

SDOH are important predictors of racial and ethnic disparities in PrEP persistence among MSM. Addressing these factors could help mitigate racial disparities in PrEP persistence in the US.
False-Positive Uptake of 123I-MIBG in the Basal Ganglion in a Pediatric Neuroblastoma Patient
Authors: Xu Yanfeng , Li Siqi , Lu Xia , Wang Wei , Yang Jigang
Published: January 2025

A 7-year-old boy with high-risk neuroblastoma underwent 123I-MIBG SPECT/CT to evaluate the therapy response. The scan revealed abnormal 123I-MIBG uptake in the left basal ganglion, indicating the possibility of brain metastasis. Subsequent contrast-enhanced brain MRI, however, did not show any abnormal signal intensity in the left basal ganglion. Follow-up 123I-MIBG SPECT/CT scans at 3-month and 9-month also did not show abnormal MIBG uptake in the same area. The case highlights the possibility of false-positive uptake of 123I-MIBG in the basal ganglion.
Serial Changes in Cranial Asymmetry During Helmet Therapy for Deformational Plagiocephaly
Authors: Tsugu Wataru , Hikosaka Makoto , Takamatsu Ako , Kaneko Tsuyoshi
Published: January 2025

Background:

To analyze the serial changes in cranial asymmetry (CA) during helmet therapy for deformational plagiocephaly (DP).

Methods:

The subjects were 159 patients with DP who visited National Center for Child Health and Development between October 2011 and March 2014 and completed helmet therapy. The authors retrospectively collected information from medical records and analyzed the rate of improvement of deformation.

Results:

The average age at the start of the helmet was 24.1 weeks old [standard deviation (SD): 5.0], and the average treatment period was 21.2 weeks (SD: 5.3). The average CA before the start of helmet therapy was 16.3 mm (SD: 4.2), and it improved to 7.7 mm (SD: 3.5) after therapy. The analysis in the present article was limited to 16 weeks after initiation of helmet therapy when 1/4 of patients completed the therapy. In general, improvement of CA occurred inverse proportionally to the enlargement of head circumference. In subgroup analysis, for those who started earlier than 24 weeks of age or those with the severity of Argenta 1 or 2, improvement occurred rapidly and reached nearly a plateau at 12 weeks of treatment. For those started later or those with more severe deformity, improvement occurred slower and it continued even after 12 weeks of treatment.

Conclusion:

The rate of improvement was rapid at the early stage of treatment for those started earlier or with milder severity. This rapid improvement was obtained when the cranial enlargement was rapid. By understanding the course of improvement, evaluation of treatment responsiveness and ideal timing to finish therapy is possible.
Injection Techniques for Filler Procedures With Illustration: Narrative Review
Authors: Hong Gi-Woong , Kim Soo-Bin , Yoon Song Eun , Wan Jovian , Felice Fernando , Velthuis Peter J. , Yi Kyu-Ho
Published: January 2025

This narrative review explores the various injection techniques utilized in facial filler procedures, emphasizing their applications, benefits, and potential complications. The increasing demand for total facial contouring and rejuvenation has led to a rise in the use of volumizing fillers and the integration of these procedures with other treatments such as toxins, threads, lasers, radiofrequency, and ultrasound. Achieving satisfactory results necessitates a comprehensive understanding of facial anatomy and the effects of aging on skin tissue. Key injection techniques discussed include retrograde and anterograde injections, linear and serial threading, serial puncture, fanning, cross-hatching, bolus, towering, sandwich, tenting, and specialized methods like fern leaf and duck walk injections. Each technique offers unique advantages, such as the retrograde technique’s ability to minimize vascular complications and the dual plane technique’s effectiveness in achieving optimal volumization and contouring by layering different types of fillers at varying depths. The dual-plane injection technique, in particular, is highlighted for its ability to provide natural and lasting results by combining firm fillers in deep layers with softer fillers superficially, minimizing surface irregularities and filler migration. The review also underscores the importance of preprocedure planning, including the marking of injection points to ensure precision, especially in patients with facial asymmetry. This comprehensive review aims to equip practitioners with the knowledge to select and master appropriate injection techniques, tailored to the specific needs of different facial areas, thereby enhancing treatment outcomes and patient satisfaction while minimizing risks.
Emergency medical services level of training is associated with mortality in trauma patients: A combined prehospital and in hospital database analysis
Authors: Harrison Julia , Bhardwaj Akshay , Houck Olivia , Sather Kristiana , Sekiya Ayako , Knack Sarah , Saarunya Clarke Geetha , Puskarich Michael A. , Tignanelli Chris , Rogers Lisa , Marmor Schelomo , Beilman Greg
Published: January 2025

BACKGROUND

There is conflicting evidence regarding emergency medical service (EMS) provider level of training and outcomes in trauma. We hypothesized that advanced life support (ALS) provider transport is associated with lower mortality compared with basic life support transport.

METHODS

We performed secondary analysis of a combined prehospital and in-hospital database of trauma patients utilizing ESO electronic medical records from 2018 to 2022. We included encounters with patients aged 15 years to 100 years transported by ground to a Level I or II trauma center with trauma-specific ICD-10-CM codes. Patients dead upon EMS arrival and transfers were excluded. We matched patients using 1:1 nearest neighbor propensity scores based on demographic, injury, and EMS characteristics, prehospital vitals, and trauma center designation. The exposure variable was EMS level of training and outcome was mortality. We conducted subgroup analyses on predefined cohorts (age > 50 years, mechanism of injury, prehospital EMS time > 30 minutes).

RESULTS

We identified 30,735 ALS and 1,758 basic life support encounters, representing 1,154 pairs following propensity matching. Mortality was lower among patients transported by ALS providers (odds ratio [OR], 0.40; 95% confidence interval [CI], 0.18–0.88; p = 0.023). Mortality was also lower in the subgroups of patients aged > 50 years (OR, 0.35; 95% CI, 0.13–0.98; p = 0.046), and in patients with mechanisms of injury excluding falls (OR, 0.35; 95% CI, 0.13–0.98; p = 0.047). In those with prolonged prehospital time, the association approached significance (OR, 0.30; 95% CI, 0.08–1.08; p = 0.067). In those with mechanisms of injury of fall, the association was not significant.

CONCLUSION

In this retrospective, propensity matched cohort study using a national sample of trauma patients, attendance by ALS providers was associated with reduced mortality. This was observed in the entire cohort, in those aged > 50 years, and those with a higher-risk mechanism of injury. It approached significance in those with prolonged prehospital time.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level III.
Association of Community Socioeconomic Distress With Waitlist and Survival Outcomes in Liver Transplantation
Authors: Sakowitz Sara , Bakhtiyar Syed Shahyan , Mallick Saad , Kaldas Fady , Benharash Peyman
Published: January 2025

Background.

Despite efforts to ensure equitable access to liver transplantation (LT), significant disparities remain. Although prior literature has considered the effects of patient sex, race, and income, the contemporary impact of community socioeconomic disadvantage on outcomes after waitlisting for LT remains to be elucidated. We sought to evaluate the association of community-level socioeconomic deprivation with survival after waitlisting for LT.

Methods.

All waitlisted candidates for isolated LT were identified using the 2005–2023 Organ Procurement and Transplantation Network. The previously validated Distressed Communities Index, representing poverty rate, median household income, unemployment, business growth, education level, and housing vacancies, was used to characterize community socioeconomic distress. Zip codes in the highest quintile were classified as the “distressed” cohort (others: “nondistressed”). Kaplan-Meier and Cox proportional hazard models were applied to assess patient and graft survival. We performed a Fine and Gray competing risk regression to consider the impact of distress on waitlist mortality.

Results.

Of 169 601 patients, 95 020 (56%) underwent LT and 74 581 (44%) remained on the waitlist. Among transplanted patients, 18 774 (20%) were distressed. After adjustment, distressed faced similar posttransplant survival at 1 y but greater mortality hazard at 5 y (hazard ratio [HR], 1.08; 95% confidence interval [CI], 1.04-1.12) and 10 y (HR, 1.09; 95% CI, 1.05-1.12). Considering all waitlisted patients, competing risk analysis demonstrated distressed candidates to face significantly greater cumulative incidence of death/deterioration on the waitlist (HR, 1.07; 95% CI, 1.04-1.11).

Conclusions.

Community-level socioeconomic inequity is associated with greater waitlist mortality and inferior post-LT survival. Novel interventions are needed to address structural barriers to care and continued inequities in outcomes.
Electrophysiological Signatures of Alpha Coma
Authors: Degano Giulio , Misirocchi Francesco , Rigoni Isotta , Kaplan Peter W. , Quintard Hervé , Vulliémoz Serge , Schaller Karl , Kleinschmidt Andreas , Seeck Margitta , De Stefano Pia
Published: January 2025

Purpose:

Recent research on quantitative EEG in coma has proposed several metrics correlating with consciousness level. However, the heterogeneous nature of coma can challenge the generalizability of these measures. This study investigates alpha-coma, an electroclinical pattern characterized by a widespread, nonreactive alpha rhythm often linked to poor outcomes. The aim was to quantify the electrophysiological features of alpha-coma and compare them to the alpha rhythm in awake controls, seeking clearer insights into quantitative EEG analysis in comatose states.

Methods:

Fourteen alpha-coma patients were retrospectively selected from University Hospitals of Geneva and age-matched with 14 healthy control subjects from an open-source dataset. EEG data were preprocessed and analyzed to extract power spectra, spectral decay (aperiodic activity), sample entropy, and functional connectivity.

Results:

Alpha-coma patients did not differ in alpha power but exhibited significantly higher levels of spectral decay (p < 0.001), suggesting a convergence toward an inhibitory state. Sample entropy was significantly higher in alpha-coma patients (p = 0.01), indicating an increase in the cortical complexity in alpha-coma compared with healthy subjects.

Conclusions:

Alpha-coma shows increased aperiodic activity and EEG complexity, despite similar alpha power and clustering coefficient. The increased aperiodic activity aligns with findings in other comatose patients, including those sedated or with subcortical dysfunction. However, the increased entropy contradicts existing literature, suggesting that alpha-coma may represent a state of widespread cortical dysfunction likely resulting from nonhierarchical, turbulent brain activity. This indicates that the loss of consciousness does not guarantee consistent cortical measures across the whole spectrum of EEG patterns.
Science and technical priorities for private sector action to address biodiversity loss
Authors: McKenzie Emily J. , Jones Matt , Seega Nina , Siikamäki Juha , Vijay Varsha
Published: January 2025

Target 15 of the Kunming–Montreal Global Biodiversity Framework recognizes the importance of the private sector monitoring, assessing and disclosing biodiversity-related risks, dependencies and impacts. Many businesses and financial institutions are progressing with science-based assessments, targets and disclosures and integrating into strategy, risk management and capital allocation decisions. Developments will continue in response to investor expectations, emerging corporate sustainability reporting regulations in Europe, China and elsewhere and evolving global sustainability reporting standards. Voluntary action is also being encouraged by the disclosure recommendations of the Taskforce on Nature-related Financial Disclosures and the target-setting methods of the Science Based Targets Network. Based on experience supporting the private sector in practice, we identify four critical science and technical advances needed to enable business action at scale and to redirect finance globally to halt and reverse biodiversity loss. First, consensus on indicators and metrics for measuring changes in the state of nature and provision of ecosystem services. Second, access to global, regularly updated, location-specific and consistent nature data. Third, standardized and consistent accounting systems that structure data, support risk management and create accountability at corporate, ecosystem and national levels. Fourth, integrated risk assessment approaches to help corporates, financial institutions, central banks and supervisors to assess nature-related risks.

This article is part of the discussion meeting issue ‘Bending the curve towards nature recovery: building on Georgina Mace's legacy for a biodiverse future’.
Bending the curve of biodiversity loss requires a ‘satnav’ for nature
Authors: Purvis Andy
Published: January 2025

Georgina Mace proposed bending the curve of biodiversity loss as a fitting ambition for the Convention on Biological Diversity. The new Global Biodiversity Monitoring Framework (GBMF) may increase the chances of meeting the goals and targets in the Kunming–Montreal Global Biodiversity Framework (KMGBF), which requires bending the curve. To meet the outcome goals of KMGBF, the GBMF should support adaptive policy responses to the state of biodiversity, which in turn requires a ‘satnav’ for nature. The twin pillars of such a satnav are (i) models to predict expected future outcomes of today’s choices; and (ii) rapid feedback from monitoring to enable course corrections and model improvement. These same elements will also empower organizations to ensure that their actions are truly nature-positive, but they are not yet written into the GBMF. Without a satnav, society will effectively have to try to find its way to the outcome goals by looking in the rear-view mirror that the current headline indicators provide. Drawing contrasts and parallels with climate modelling, I discuss challenges for indicators, models, data and research culture that must be overcome if we are to bend the curve, and suggest ways forward.

This article is part of the discussion meeting issue ‘Bending the curve towards nature recovery: building on Georgina Mace's legacy for a biodiverse future’.
Whose conservation, revisited: how a focus on people–nature relationships spotlights new directions for conservation science
Authors: Reyers Belinda , Bennett Elena M.
Published: January 2025

Georgina Mace introduced a compelling perspective on the major shifts in conservation science’s framing and purpose from 1960 to 2010. A decade ago, she proposed that the conservation community had begun to move into a new framing of ‘people and nature’ based on changes in perspectives on the relationships between people and nature and new interdisciplinary concepts and methods used in conservation. Progress in using this frame is clear as ‘two-way dynamic relationships between people and nature’ have since taken centre stage in science, practice and policy. Now, responding to concerns raised that current approaches to conservation are still not meeting the scale and complexity of the challenges of the Anthropocene, we explore a newly emerging framing of ‘people with nature’—an inextricably intertwined perspective on people–nature relationships. This framing builds on Mace’s recognition of interconnections and change, as well as new directions offered by conservation’s recent transdisciplinary engagements, to go beyond the notion of two-way flows connecting people and nature to emphasize the relationships and inseparability of ‘people with nature’. This emerging framing suggests new directions for conservation science and practice to make visible, improve and reimagine degraded people–nature relationships needed to bend the curve of biodiversity loss.

This article is part of the discussion meeting issue ‘Bending the curve towards nature recovery: building on Georgina Mace's legacy for a biodiverse future’.