bluuebunny/crossref_metadata_2025 huggingface dataset:
706 Mobilization with Femoral Catheters in the Burn ICU: Retrospective Review of Practice Guidelines
Authors: O'Neil Audrey M , Rush Cassandra , Boyd Allison N , Roggy David , Hartman Brett C
Published: April 2024

Introduction

Femoral catheters are a known barrier for ICU therapy sessions and mobility progression due to the anatomical location and potential risk of complications. Mobilization with femoral catheters has been studied in ICU populations, but has not been explored specifically within the burn population. A previous case series was completed in 2022, examining the safety of mobilization with femoral catheters in the burn ICU, following a change in practice guidelines. The purpose of this study is to further examine outcomes and complication rates following implementation of femoral catheter mobilization guidelines, as well as retrospectively compare data to outcomes prior to initiation of the mobilization protocol.

Methods

Retrospective review was completed on 17 patients prior to and following implementation of new femoral catheter mobility guidelines within a 15-bed adult burn unit, 34 patients total. Burn therapy notes were reviewed for burn admissions with at least one femoral catheter in place, including arterial, central, and dialysis catheters. Demographic data, admission statistics, line placement timelines, and active mobility achieved during therapy sessions were recorded for both the non-mobilization (NMG) and mobilization groups (MG).

Results

The 34 patients reviewed had 99 total lines placed (30 NMG, 69 MG). Mobilization restrictions limited the NMG group resulting in less therapy sessions (n=281), active mobility sessions (n=5), and mobility activities (n=6). Change in mobility protocols for the MG group resulted significantly more therapy sessions (n=516) and active mobility sessions (n=83), including 146 total mobility activities including transitions to chair mode of bed, cardiac chair, tilt table, sitting edge of bed (EOB), standing, active chair transfers, and cycle ergometry. Additionally, 82% (n=14) of patients in the MG participated in mobility earlier, while intubated, while the NMG was unable to participate in out of bed activity while intubated. No catheter associated adverse events occurred during active mobility sessions and no complications were associated with participation in mobility.

Conclusions

Establishing femoral catheter mobility guidelines allowed patients with femoral catheters to participate in significantly greater active therapy sessions, compared to previously restricted groups, without compromising safety. Early mobilization within ICU settings is necessary in preventing complications, combating muscle wasting, and improving long term outcomes for survivors. This study further supports that the presence of femoral catheters alone should not limit the progression of mobility interventions.

Applicability of Research to Practice

Therapy driving mobilization guidelines are safe within the burn ICU setting, when proper training and staff resources are present. Change in practice guidelines allowed significant improvements in patient access to active therapy interventions.
730 Does Post-hospitalization Outreach Create a Sustainable Burn Survivor Community?
Authors: Stephan Rana M , Vargas Vina , Sheckter Clifford C
Published: April 2024

Introduction

Burn survivors face many challenges after injury. Physical challenges include persistent wounds, scar contractures, thermal body dysregulation, and loss of limb. The psychological challenges can be equally challenging. Confronting isolation, depression, anxiety, post-traumatic stress, guilt, and change in body image are some of the many obstacles burn survivors face. However, a burn survivor’s participation in a burn community has shown to help alleviate the stress of reintegration by improving social interaction, maintaining friendships, improving body image, and giving tools to communicate. We hypothesize that post-hospital outreach develops a sustainable community for burn survivors.

Methods

Burn survivor outreach begins during hospitalization. Burn center staff are versed on the spectrum of outreach services, and patients are invited to partake in events, as appropriate. Support group is the primary introduction to outreach services, as patients and survivors are invited to a monthly group. Additionally, post-hospital outreach consists of regular community events, recreational programs, one-on-one peer support, virtual support group and volunteer opportunities. Participation in burn outreach is voluntary at the time of hospitalization and at discharge, with patients agreeing to receive monthly burn newsletter with information about community outreach events, including support group. All voluntary participants were reviewed from 2018 – 2023 from an ABA verified burn center. Survivor community sustainability was measured by the number of survivors coming to support group.

Results

Support groups were held monthly from 2018-2023, totally 69 sessions involving 61 burn staff. During the COVID-19 pandemic, support group was adapted to online version for 20 months. Post-pandemic, support group has been conducted hybrid (virtual and in-person). 372 burn survivors agreed to receive information about community outreach and support group of which 49% (182) participated. Of the 182 that participated, 111 were female and 71 were male. 11 brought family to support group. 113 participants only attended one session, while 90 participants attended two or more. Attendance ranged from 2 to 50, with a median of 25 in attendance. The median number of sessions attended per survivor was 4.0 for all-comers and 9.2 for those who attended 2 or more sessions.

Conclusions

Burn survivor support group demonstrated consistent participation validating its purpose. Through building a community, psychological healing continues post-hospitalization. Furthermore, the sense of burn community is deepened by not only by continued participation in group but also by survivors extending into other outreach events.

Applicability of Research to Practice

Regular support group creates a sustainable burn survivor community for those interested in participation. The hybrid format is conducive to many lifestyles and can be adopted by burn centers across the US.
736 Health Literacy in Patients with Burn Injury
Authors: Morzycki Alexander , Eschelbach Emily , Sharma Ayana , Oh Jamie , Battiston Adrian , Wong Joshua N , Pham Tam N
Published: April 2024

Introduction

Burn injuries occur with a disproportionately higher frequency in vulnerable groups. Their health literacy (HL), defined as the way patients obtain, process, and understand health information, may be an important factor that influences access, care, and recovery after burns. This study aims to determine the current levels of health literacy and variables associated with poor health literacy for outpatients treated at two regional burn centres.

Methods

All eligible patients presenting to two tertiary outpatient burn centers were asked to participate. The Newest Vital Sign health literacy assessment tool and a sociodemographic survey were administered. The NVS scores were divided into poor (0-2), moderate (3-4), and adequate (5-6) health literacy. We first compared health literacy rates between sites using non-parametric Chi-squared test. We then developed a multivariable regression model using a stepwise construction with poor health literacy as our dependent variable. Included in the exploratory model were income, education level, working status, and age.

Results

Forty-nine patients with a mean age of 46.6 years (SD=17.4) were included; 57% (29/49) of patients identified as male. Most of the burn injuries (78%, 38/49) were less than 10% total body surface area. HL rates were poor, moderate, and adequate in 35% (17/49), 18% (9/29), and 47% (23/29), respectively. There were no differences in health literacy between the 2 sites. Age was the only independent predictor of poor health literacy in burn patients, with advanced age being associated with worse health literacy (95% CI: 1.001-1.119, p< 0.05). Income, education level and working status did not independently predict health literacy rates (Table 1).

Conclusions

More than half of patients treated at burn outpatient clinics have only poor or moderate health literacy. This study further suggests that older adults may be most at risk. This trend is consistent across two regional burn centres. This study highlights the importance of health literacy among patients with burn injury and stresses the importance of personalized and literacy-adjusted discussions surrounding care. Our next project will address the impact of health literacy on adherence to recommended therapies.

Applicability of Research to Practice

Poor health literacy is a barrier to obtaining burn care and is an important social determinant of health. We should identify factors associated with poor health literacy among patients with burn injury and improve the delivery of health information.
Temporal genomics help in deciphering neutral and adaptive patterns in the contemporary evolution of kelp populations
Authors: Reynes Lauric , Fouqueau Louise , Aurelle Didier , Mauger Stéphane , Destombe Christophe , Valero Myriam
Published: April 2024

The impact of climate change on populations will be contingent upon their contemporary adaptive evolution. In this study, we investigated the contemporary evolution of 4 populations of the cold-water kelp Laminaria digitata by analyzing their spatial and temporal genomic variations using ddRAD-sequencing. These populations were sampled from the center to the southern margin of its north-eastern Atlantic distribution at 2 time points, spanning at least 2 generations. Through genome scans for local adaptation at a single time point, we identified candidate loci that showed clinal variation correlated with changes in sea surface temperature (SST) along latitudinal gradients. This finding suggests that SST may drive the adaptive response of these kelp populations, although factors such as species’ demographic history should also be considered. Additionally, we performed a simulation approach to distinguish the effect of selection from genetic drift in allele frequency changes over time. This enabled the detection of loci in the southernmost population that exhibited temporal differentiation beyond what would be expected from genetic drift alone: these are candidate loci which could have evolved under selection over time. In contrast, we did not detect any outlier locus based on temporal differentiation in the population from the North Sea, which also displayed low and decreasing levels of genetic diversity. The diverse evolutionary scenarios observed among populations can be attributed to variations in the prevalence of selection relative to genetic drift across different environments. Therefore, our study highlights the potential of temporal genomics to offer valuable insights into the contemporary evolution of marine foundation species facing climate change.
An iterative Kalman filter-based method for traveltime tomography
Authors: Zhang Yun , Li Xihai , Liu Tian , Liu Jihao , Bai Chaoying
Published: April 2024

In addition to directly determining the inverted velocity, it is crucial to assess the uncertainty (or confidence) of the relevant velocity imaging results. This is especially true when dealing with time-lapse seismic data, which play a crucial role in detecting changes in fluid movement in petroleum reservoirs. In this study, we developed an iterative Kalman filter-based method to monitor time-lapse changes in the subsurface using traveltime tomography. Our approach considers the uncertainty of the results. We successfully verified the validity of our proposed method through synthetic crosshole and time-lapse tests. Our iterative Kalman filter-based method provides reasonable reconstruction results suitable for accessing uncertainties, and the algorithm can be used to monitor changes in the subsurface medium.
Induced regulatory T cells as immunotherapy in allotransplantation and autoimmunity: challenges and opportunities
Authors: Alvarez-Salazar Evelyn Katy , Cortés-Hernández Arimelek , Arteaga-Cruz Saúl , Soldevila Gloria
Published: April 2024

Regulatory T cells play a crucial role in the homeostasis of the immune response. Regulatory T cells are mainly generated in the thymus and are characterized by the expression of Foxp3, which is considered the regulatory T-cell master transcription factor. In addition, regulatory T cells can be induced from naive CD4+ T cells to express Foxp3 under specific conditions both in vivo (peripheral regulatory T cells) and in vitro (induced regulatory T cells). Both subsets of thymic regulatory T cells and peripheral regulatory T cells are necessary for the establishment of immune tolerance to self and non-self antigens. Although it has been postulated that induced regulatory T cells may be less stable compared to regulatory T cells, mainly due to epigenetic differences, accumulating evidence in animal models shows that induced regulatory T cells are stable in vivo and can be used for the treatment of inflammatory disorders, including autoimmune diseases and allogeneic transplant rejection. In this review, we describe the biological characteristics of induced regulatory T cells, as well as the key factors involved in induced regulatory T-cell transcriptional, metabolic, and epigenetic regulation, and discuss recent advances for de novo generation of stable regulatory T cells and their use as immunotherapeutic tools in different experimental models. Moreover, we discuss the challenges and considerations for the application of induced regulatory T cells in clinical trials and describe the new approaches proposed to achieve in vivo stability, including functional or metabolic reprogramming and epigenetic editing.
ZCCHC17 knockdown phenocopies Alzheimer’s disease-related loss of synaptic proteins and hyperexcitability
Authors: Cortese Giuseppe P , Bartosch Anne Marie W , Xiao Harrison , Gribkova Yelizaveta , Lam Tiffany G , Argyrousi Elentina K , Sivakumar Sharanya , Cardona Christopher , Teich Andrew F
Published: April 2024

ZCCHC17 is a master regulator of synaptic gene expression and has recently been shown to play a role in splicing of neuronal mRNA. We previously showed that ZCCHC17 protein declines in Alzheimer’s disease (AD) brain tissue before there is significant gliosis and neuronal loss, that ZCCHC17 loss partially replicates observed splicing abnormalities in AD brain tissue, and that maintenance of ZCCHC17 levels is predicted to support cognitive resilience in AD. Here, we assessed the functional consequences of reduced ZCCHC17 expression in primary cortical neuronal cultures using siRNA knockdown. Consistent with its previously identified role in synaptic gene expression, loss of ZCCHC17 led to loss of synaptic protein expression. Patch recording of neurons shows that ZCCHC17 loss significantly disrupted the excitation/inhibition balance of neurotransmission, and favored excitatory-dominant synaptic activity as measured by an increase in spontaneous excitatory post synaptic currents and action potential firing rate, and a decrease in spontaneous inhibitory post synaptic currents. These findings are consistent with the hyperexcitable phenotype seen in AD animal models and in patients. We are the first to assess the functional consequences of ZCCHC17 knockdown in neurons and conclude that ZCCHC17 loss partially phenocopies AD-related loss of synaptic proteins and hyperexcitability.
Elite lawyers in Türkiye: Educational capital, status hierarchies, and feminization
Authors: Koytak Elyesa
Published: April 2024

Sociological studies on elite lawyers working in large law firms have recently extended to non-Western countries. Based on a quantitative dataset comprising 1,303 lawyers from 106 Turkish law firms, this article aims to be the first empirical investigation of the social profile of lawyers in the rising large law firms in Türkiye. The analysis focuses on how characteristics of Turkish elite lawyers, in terms of educational capital, gender, and status are distributed. The objective of the analysis is to discover to what extent the expansion of legal education and rise of the private universities are reflected in the structure of elite law firms. To discover the relationships between university type, gender, and position at job, chi-square, and logistic regression analyses are conducted. Main findings are that the Turkish elite lawyers constitute a stratum where the most advantageous educational capital is concentrated compared to the profession in general, the lawyers working in the employee position are relatively young and have mostly private university degrees, and the increased feminization of the profession is closely intertwined with the status hierarchies.
The relationship between female orgasmic disorder, attention-deficit/hyperactivity disorder, and depression in Dominican women
Authors: Alarcon-Rodriguez Raquel , García-Álvarez Rafael , Fadul-Calderon Rosario , Romero-del Rey Raúl , Requena-Mullor Mar , Read Tejada Madelyn , Garcia-Gonzalez Jessica
Published: April 2024

Background

Female orgasmic disorder is listed in the DSM-5 and is defined as the persistent or recurrent inability to have an orgasm. Many depressed women may experience sexual dysfunction, including female orgasmic disorder.

Aim

The study sought to analyze the relationship between depressive disorders and attention-deficit/hyperactivity disorder (ADHD) and their influence on the development of female orgasmic disorder.

Methods

A total of 221 Dominican women participated in this case-control study. The case group consisted of 107 women diagnosed with female orgasmic disorder, while the control group consisted of 114 women without any sexual dysfunction.

Outcomes

The diagnosis of ADHD was obtained from the participants’ medical records, previously conducted using the DSM-5-TR criteria. The Beck Depression Inventory II was used to assess the severity of depressive symptoms in both groups.

Results

There was a significant relationship between female orgasmic disorder and ADHD and depression. The results of multiple logistic regression indicated that the highest risk of female orgasmic disorder was observed in women with ADHD (odds ratio [OR], 4.91; 95% confidence interval [CI], 2.46-9.20; P < .001), women with severe depression (OR, 2.50; 95% CI, 1.08-6.96; P = .04), and women who had sexual intercourse that focused on penetration (OR, 2.02; 95% CI, 1.03-3.98; P = .04).

Clinical Implications

These findings may have important implications for the prevention and treatment of sexual disorders in women.

Strengths and Limitations

This design selected all diagnosed cases of female orgasmic disorder and did not select a specific subgroup. However, some limitations must be considered. This study was conducted in a single clinic, although it should be noted that it is the main clinic for the treatment of sexual dysfunction in the country. A further limitation could be that this type of study design does not allow for statements about causality to be made.

Conclusion

There is an increased risk of female orgasmic disorder in women with ADHD, with severe depression, and who engage in penetrative sex.
Growth conditions trigger genotype-specific metabolic responses that affect the nutritional quality of kale cultivars
Authors: Ishihara Hirofumi , Alegre Sara , Pascual Jesús , Trotta Andrea , Yang Wei , Yang Baoru , Seyednasrollah Fatemeh , Burow Meike , Kangasjärvi Saijaliisa
Published: April 2024

Kales (Brassica oleracea convar. acephala) are fast-growing, nutritious leafy vegetables ideal for year-round indoor farming. However, selection of the best cultivars for growth under artificial lighting necessitates a deeper understanding of leaf metabolism in different kale types. Here we examined a curly-leaved cultivar, Half Tall, and a lacinato-type cultivar, Black Magic, under moderate light (130 µmol photons m−2 s−1/22 °C) and high light (800 µmol photons m−2 s−1/26 °C) conditions. These conditions induced genotype-dependent differences in nutritionally important metabolites, especially anthocyanins and glucosinolates (GSLs), in kale cultivars. In the pale green Half Tall, growth under high light conditions did not induce changes in either pigmentation or total GSL content. In contrast, the purple pigmentation of Black Magic intensified due to increased anthocyanin accumulation. Black Magic showed reduced contents of indole GSLs and increased contents of aliphatic GSLs under high light conditions, with notable cultivar-specific adjustments in individual GSL species. Correlation analysis of metabolite profiles suggested cultivar-specific metabolic interplay between serine biosynthesis and the production of indole GSLs. RNA sequencing identified candidate genes encoding metabolic enzymes and regulatory components behind anthocyanin and GSL biosynthesis. These findings improve our understanding of leaf metabolism and its effects on the nutritional quality of kale cultivars.
Comparison of fungemia caused by Candida and non-Candida rare yeasts: a retrospective study from a tertiary care hospital
Authors: Oz Yasemin , Yılmaz Mustafa , Bulduk Tuba , Basayigit Mehmet , Gunduz Eren , Metintas Selma
Published: April 2024

Although Candida species are the most common cause of fungemia, non-Candida rare yeasts (NCY) have been increasingly reported worldwide. Although the importance of these yeast infections is recognized, current epidemiological information about these pathogens is limited, and they have variable antifungal susceptibility profiles. In this study, we aimed to evaluate the clinical characteristics for fungemia caused by NCY by comparing with candidemia. The episodes of NCY fungemia between January 2011 and August 2023 were retrospectively evaluated in terms of clinical characteristics, predisposing factor, and outcome. In addition, a candidemia group, including patients in the same period was conducted for comparison. Antifungal susceptibility tests were performed according to the reference method. A total of 85 patients with fungemia episodes were included: 25 with NCY fungemia and 60 with candidemia. Fluconazole had high minimal inhibitory concentration (MIC) values against almost all NCY isolates. The MIC values for voriconazole, posaconazole, and amphotericin B were ≤ 2 µg/ml, and for caspofungin and anidulafungin were ≥ 1 µg/ml against most of isolates. Hematological malignancies, immunosuppressive therapy, neutropenia and prolonged neutropenia, polymicrobial bacteremia/fungemia, preexposure to antifungal drugs, and breakthrough fungemia were associated with NCY fungemia, whereas intensive care unit admission, diabetes mellitus, urinary catheters, and total parenteral nutrition were associated with candidemia. In conclusion, the majority of fungemia due to NCY species was the problem, particularly in hematology units and patients with hematological malignancy. Preexposure to antifungal drugs likely causes a change in the epidemiology of fungemia in favor of non-albicans Candida and/or NCY.
Green banana biomass anti-obesogenic, anti-hyperlipidemic, antidiabetic, and intestinal function potential effects: a systematic review
Authors: da Silva Bomfim Natália , de Souza Ferreira Renata , Silva e Oliveira Julia , de Cássia Gonçalves Alfenas Rita
Published: April 2024

Context

Apparently, the consumption of resistant-starch food sources, such as green banana biomass, stimulates the proliferation of short-chain fatty acid intestinal bacteria producers, which can contribute to intestinal health and reduce the risk of chronic diseases. However, the available scientific evidence is scarce and no study has systematically evaluated such evidence.

Objective

The aim of this study was to analyze the potential effects of green banana biomass on anthropometry, body composition, and biochemical and intestinal variables in humans and animals.

Data Sources

The Cochrane Library, Embase, Medline/PubMed, Scopus, and Web of Science electronic databases were searched in January 2024 for eligible articles. Studies that tested the effects of cooked peeled or unpeeled green banana on anthropometric, biochemical, and/or intestinal variables were included.

Data Extraction

This systematic review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The classification and assessment of the quality of studies were based on the relevant criteria related to the design of these studies and the quality criteria checklist of the Academy of Nutrition and Dietetics manual. Twelve studies published between 2001 and 2021 were included in the review.

Data Analysis

The results of human studies indicate that the ingestion of green banana biomass controlled intestinal dysfunction (50–300 g/day for 5–14 days or 30 g/day for 8 wk) in children, and showed potential anti-obesogenic, anti-hyperlipidemic, and antidiabetic (40 g/day for 24 wk) effects in adults. In rats, biomass consumption led to potential anti-obesogenic (25 g/day for 8 wk), anti-hyperlipidemic, and antidiabetic (∼8–30 g/day for 12 wk) effects.

Conclusion

Consumption of green banana biomass seems to exert beneficial effects on intestinal function and potential effects on obesity, dyslipidemia, and diabetes. These effects may be related to increased fecal short-chain fatty acid concentrations as a result of type 3 resistant starch present in biomass.

Systematic Review Registration

Open Science Framework (OSF) (https://doi.org/10.17605/OSF.IO/TKCWV).
Sequence Analysis of Inducible, Replication-Competent Virus Reveals No Evidence of HIV-1 Evolution During Suppressive Antiviral Therapy, Indicating a Lack of Ongoing Viral Replication
Authors: Lee Sook-Kyung , Sondgeroth Amy , Xu Yinyan , Warren Joanna , Zhou Shuntai , Gilleece Maria , Hauser Blake M , Gay Cynthia L , Kuruc JoAnn D , Archin Nancie M , Eron Joseph J , Margolis David M , Goonetilleke Nilu , Swanstrom Ronald
Published: April 2024

Background

Persistence of HIV-1 in reservoirs necessitates life-long antiretroviral therapy (ART). There are conflicting data using genetic analysis on whether persistence includes an actively replicating reservoir with strong evidence arguing against replication.

Methods

We investigated the possibility of ongoing viral evolution during suppressive therapy by comparing near full-length viral genomic sequences using phylogenetic analysis of viral RNA in plasma before therapy initiation early after infection and from virus induced to grow from the latent reservoir after a period of suppressive ART. We also focused our analysis on evidence of selective pressure by drugs in the treatment regimen and at sites of selective pressure by the adaptive immune response.

Results

Viral genomes induced to grow from the latent reservoir from 10 participants with up to 9 years on suppressive ART were highly similar to the nearly homogeneous sequences in plasma taken early after infection at ART initiation. This finding was consistent across the entire genome and when the analysis focused on sites targeted by the drug regimen and by host selective pressure of antibody and cytotoxic T cells. The lack of viral evolution away from pretherapy sequences in spite of demonstrated selective pressure is most consistent with a lack of viral replication during reservoir persistence.

Conclusions

These results do not support ongoing viral replication as a mechanism of HIV-1 persistence during suppressive ART.
Role of Routine Suppressive Antibiotic Therapy After Debridement, Antibiotics, and Implant Retention for Acute Periprosthetic Joint Infections
Authors: Tai Don Bambino Geno , Tande Aaron J , Langworthy Benjamin , Abdel Matthew P , Berbari Elie F , ten Have Bas , Jutte Paul , Soriano Alex , Suh Gina A , Zijlstra Wierd , Wouthuyzen-Bakker Marjan
Published: April 2024

Background

The first-line management strategy for acute periprosthetic joint infections (PJIs) is debridement, antibiotics, and implant retention (DAIR). Suppressive antibiotic therapy (SAT) after DAIR is proposed to improve outcomes, yet its efficacy remains under scrutiny.

Methods

We conducted a multicenter retrospective study in patients with acute PJI of the hip or knee who were treated with DAIR in centers from Europe and the United States. We analyzed the effect of SAT using a Cox model landmarked at 12 weeks. The primary covariate of interest was SAT, which was analyzed as a time-varying covariate. Patients who experienced treatment failure or were lost to follow-up within 12 weeks were excluded from the analysis.

Results

The study included 510 patients with 66 treatment failures with a median follow-up of 801 days. We did not find a statistically significant association between SAT and treatment failure (hazard ratio, 1.37; 95% CI, .79–2.39; P = .27). Subgroup analyses for joint, country cohort, and type of infection (early or late acute) did not show benefit for SAT. Secondary analysis of country cohorts showed a trend toward benefit for the US cohort (hazard ratio, 0.36; 95% CI, .11–1.15; P = .09), which also had the highest risk of treatment failure.

Conclusions

The utility of routine SAT as a strategy for enhancing DAIR's success in acute PJI remains uncertain. Our results suggest that SAT's benefits might be restricted to specific groups of patients, underscoring the need for randomized controlled trials. Identifying patients most likely to benefit from SAT should be a priority in future studies.
Evolving assessment pathways for precision oncology medicines to improve patient access: a tumor-agnostic lens
Authors: Radu Priscila , Kumar Gayathri , Cole Amanda , Fameli Aikaterini , Guthrie Mark , Annemans Lieven , Geissler Jan , Italiano Antoine , O’Rourke Brian , Xoxi Entela , Steuten Lotte
Published: April 2024

Background

Genomic and molecular alterations are increasingly important in cancer diagnosis, and scientific advances are opening new treatment avenues. Precision oncology (PO) uses a patient’s genomic profile to determine optimal treatment, promising fewer side effects and higher success rates. Within PO, tumor-agnostic (TA) therapies target genomic alterations irrespective of tumor location. However, traditional value frameworks and approval pathways pose challenges which may limit patient access to PO therapies.

Objectives

This study describes challenges in assessing PO and TA medicines, explores possible solutions, and provides actionable recommendations to facilitate an iterative life-cycle assessment of these medicines.

Methods

After reviewing the published literature, we obtained insights from key stakeholders and European experts across a range of disciplines, through individual interviews and an industry workshop. The research was guided and refined by an international expert committee through 2 sounding board meetings.

Results

The current challenges faced by PO and TA medicines are multiple and can be demonstrated through real-world examples of the current barriers and opportunities. A life-cycle approach to assessment should be taken, including key actions at the early stages of evidence generation, regulatory and reimbursement stage, as well as payment and adoption solutions that make use of the evolving evidence base. Working toward these solutions to maximize PO medicine value is a shared responsibility and stands to benefit all stakeholders.

Conclusions

Our call to action is to expand access to comprehensive genomic testing, foster a learning health care system, enable fast and equitable access to cost-effective treatments, and ultimately improve health outcomes.
Human malignancies associated with persistent HPV infection
Authors: McBride Alison A
Published: April 2024

Human papillomavirus (HPV)-associated malignancies account for ~5% of human cancers worldwide. Thirteen, or more, HPV types are oncogenic, but infection with these viruses is common and usually cleared within 2 years. Only infections that become persistent are associated with the development of cancer, often occurring several decades later. These cancers mostly arise in 6 different anatomical regions: 5 are anogenital (anus, cervix, penis, vagina, and vulva) and the sixth is the oropharynx. Oncogenic HPVs promote cellular proliferation and genomic instability, but the anatomical niche of the target tissue also plays an important role in the development of cancer. Cells that reside in transitional regions between different types of epithelia, such as in the anus, cervix, and oropharynx, are particularly vulnerable to oncogenesis.
The GRAS transcription factor CsTL regulates tendril formation in cucumber
Authors: Shen Junjun , Jiang Yanxin , Pan Jian , Sun Linhan , Li Qingqing , He Wenjing , Sun Piaoyun , Zhao Bosi , Zhao Hongjiao , Ke Xubo , Guo Yalu , Yang Tongwen , Li Zheng
Published: April 2024

Cucumber (Cucumis sativus, Cs) tendrils are slender vegetative organs that typically require manual removal to ensure orderly growth during greenhouse cultivation. Here, we identified cucumber tendril-less (tl), a Tnt1 retrotransposon-induced insertion mutant lacking tendrils. Map-based cloning identified the mutated gene, CsaV3_3G003590, which we designated as CsTL, which is homologous to Arabidopsis thaliana LATERAL SUPPRESSOR (AtLAS). Knocking out CsTL repressed tendril formation but did not affect branch initiation, whereas overexpression (OE) of CsTL resulted in the formation of two or more tendrils in one leaf axil. Although expression of two cucumber genes regulating tendril formation, Tendril (CsTEN) and Unusual Floral Organs (CsUFO), was significantly decreased in CsTL knockout lines, these two genes were not direct downstream targets of CsTL. Instead, CsTL physically interacted with CsTEN, an interaction that further enhanced CsTEN-mediated expression of CsUFO. In Arabidopsis, the CsTL homolog AtLAS acts upstream of REVOLUTA (REV) to regulate branch initiation. Knocking out cucumber CsREV inhibited branch formation without affecting tendril initiation. Furthermore, genomic regions containing CsTL and AtLAS were not syntenic between the cucumber and Arabidopsis genomes, whereas REV orthologs were found on a shared syntenic block. Our results revealed not only that cucumber CsTL possesses a divergent function in promoting tendril formation but also that CsREV retains its conserved function in shoot branching.
A pipeline for identification of causal mutations in barley identifies Xantha-j as the chlorophyll synthase gene
Authors: Stuart David , Zakhrabekova Shakhira , Jørgensen Morten Egevang , Dockter Christoph , Hansson Mats
Published: April 2024

Thousands of barley (Hordeum vulgare L.) mutants have been isolated over the last century, and many are stored in gene banks across various countries. In the present work, we developed a pipeline to efficiently identify causal mutations in barley. The pipeline is also efficient for mutations located in centromeric regions. Through bulked segregant analyses using whole genome sequencing of pooled F2 seedlings, we mapped 2 mutations and identified a limited number of candidate genes. We applied the pipeline on F2 mapping populations made from xan-j.59 (unknown mutation) and xan-l.82 (previously known). The Xantha-j (xan-j) gene was identified as encoding chlorophyll synthase, which catalyzes the last step in the chlorophyll biosynthetic pathway: the addition of a phytol moiety to the propionate side chain of chlorophyllide. Key amino acid residues in the active site, including the binding sites of the isoprenoid and chlorophyllide substrates, were analyzed in an AlphaFold2-generated structural model of the barley chlorophyll synthase. Three allelic mutants, xan-j.19, xan-j.59, and xan-j.64, were characterized. While xan-j.19 is a 1 base pair deletion and xan-j.59 is a nonsense mutation, xan-j.64 causes an S212F substitution in chlorophyll synthase. Our analyses of xan-j.64 and treatment of growing barley with clomazone, an inhibitor of chloroplastic isoprenoid biosynthesis, suggest that binding of the isoprenoid substrate is a prerequisite for the stable maintenance of chlorophyll synthase in the plastid. We further suggest that chlorophyll synthase is a sensor for coordinating chlorophyll and isoprenoid biosynthesis.
On the Margins of Maternity: Low-Income Women’s Experiences of Maternity Care in Late Twentieth-Century Glasgow
Authors: Greenlees Janet
Published: April 2024

The healthcare provided to expectant mothers impacts the health outcomes of the mother and infant, or infants, and reflects current social and political priorities which mirror middle-class values and leave poorer women feeling socially isolated. Utilising focus group interviews with nineteen women who were living on low-incomes in Glasgow, Scotland, when they delivered their first child between the 1970s and early 2000s, this article analyses the women’s recollections of their maternity care experiences within the changing middle-class health context. It reveals how expectant mothers remembered feeling healthcare practitioners prioritised the needs of the embryo/foetus/infant before their own. The women recalled feeling stigmatised for being pregnant and poor. While interviewees identified individual caring practitioners, overall a disconnect remained between the middle-class healthcare providers and the needs of low-income mothers. Finally, this article suggests that co-creating history with a third-sector organisation could offer a potential methodology for addressing the middle-class bias of official sources.
Effect of dynamic binaural beats on sleep quality: a proof-of-concept study with questionnaire and biosignals
Authors: Lee Hwa-Ah-Ni , Lee Woo-Jin , Kim Seong-Uk , Kim Hyunji , Ahn Minkyu , Kim Jeonghui , Kim Do-Won , Yun Chang-Ho , Hwang Han-Jeong
Published: April 2024

Binaural beat (BB) has been investigated as a potential modality to enhance sleep quality. In this study, we introduce a new form of BB, referred to as dynamic BB (DBB), which incorporates dynamically changing carrier frequency differences between the left and right ears. Specifically, the carrier frequency of the right ear varied between 100 and 103 Hz over a period, while the left ear remained fixed at 100 Hz, yielding a frequency difference range of 0 to 3 Hz. The objective of this study was to examine the effect of DBB on sleep quality. Ten healthy participants were included in a cross-over design, where they experienced both DBB and a SHAM (absence of sound) condition across two consecutive nights, with polysomnography evaluation. DBB was administrated during pre-sleep initiation, sleep onset, and transition from rapid eye movement (REM) to non-REM stage. DBB significantly reduced sleep latency compared to the SHAM condition. Electrocardiogram analysis revealed that exposure to DBB led to diminished heart rate variability during the pre-sleep initiation and sleep onset periods, accompanied by a decrease in low-frequency power of heart rate during the sleep onset period. DBB might be effective in improving sleep quality, suggesting its possible application in insomnia treatments.
A Scaphoid Safety Scapholunate Interosseous Ligament Reconstruction. The Non–Bone Tunnel Technique and Clinical Outcomes
Authors: Tuntiyatorn Panithan , Rojpitipongsakorn Chanakarn , Chulsomlee Kulapat , Pittayasoponkij Pongsakorn , Kanchanathepsak Thepparat , Tawonsawatruk Tulyapruek
Published: April 2024

Objective:

In the chronic unrepairable scapholunate interosseous ligament (SLIL) injury stage, scapholunate ligament (SL) reconstruction remains the gold standard treatment. However, most surgical techniques are required to make the bone tunnel by drilling through the scaphoid, which may introduce iatrogenic scaphoid fracture as a complication. Thus, the aim of this study was to describe an alternative surgical technique for SLIL reconstruction by using a double anchor suture instead of bone drilling.

Materials and Methods:

A total of 5 consecutive cases of chronic scapholunate dissociation that underwent the non–bone tunnel technique of SLIL reconstruction were included in the study. The clinical data between the preoperative and postoperative were collected.

Results:

In 5 cases, a ligament reconstruction was achieved successfully. At 12 weeks after the surgery. The average Visual Analog Scale improved from 8.4 to 1.0. The clinical stress test was negative without pain. The mean grip strength improved to 85.4% compared with the normal contralateral hand. The mean Quick Disabilities of the Arm, Shoulder, and Hand score was 8.62 compared with the preoperative score of 70.92. Mean of SL interval in wrist with anteroposterior view and anteroposterior clenched fist view at 2.50 mm and 2.68 mm.

Conclusion:

The scaphoid safety SLIL reconstruction technique is a simple and reliable treatment method, using flexor carpi radialis tendon weave and anchor-ligament-anchor procedure instead of previous bone tunnel techniques. Biomechanical strength of the system demonstrated by postoperative results of scaphoid flexion was corrected, but SL gaps were still remaining in some cases. However, there was no effect on clinical outcomes and patient satisfaction.
The Impact of Surgical Delay in Primary Cutaneous Melanoma: A Systematic Review
Authors: Zhang Michael Z. , Hines Alexander S. , Demer Addison M. , Brewer Jerry D.
Published: April 2024

BACKGROUND AND OBJECTIVES

The prognosis of patients diagnosed with melanoma is highly dependent on staging, early detection, and early intervention. In this systematic review, the authors aimed to investigate the impact of surgical delay (time between diagnostic biopsy and definitive surgical excision) on melanoma-specific outcomes.

MATERIAL AND METHODS

A systematic review was conducted from Embase (1974–present), MEDLINE (1946–present), Cochrane Central Register of Controlled Trials (2005–present), Scopus, and Web of Science. A total of 977 studies were included for review after removal of duplicates. A total of 10 studies were included for final analysis.

RESULTS

In total, 70% (7/10) of the studies found that longer wait times between initial biopsy and surgical intervention are correlated with lower overall survival. Among the 9 studies that reported overall survival as a percentage, the median and SD overall survival was 82% ± 5.87.

CONCLUSION

There is evidence that prolonged surgical delay in patients diagnosed with Stage I cutaneous melanoma is associated with worsened overall mortality, whereas the effect of surgical delay on overall mortality in Stages II and III melanomas is uncertain. Future prospective studies and randomized clinical trials are needed to better define the appropriate surgical wait times between biopsy and surgical treatment.
A Quantitative Bias Analysis Approach to Informative Presence Bias in Electronic Health Records
Authors: Zhang Hanxi , Clark Amy S. , Hubbard Rebecca A.
Published: April 2024

Accurate outcome and exposure ascertainment in electronic health record (EHR) data, referred to as EHR phenotyping, relies on the completeness and accuracy of EHR data for each individual. However, some individuals, such as those with a greater comorbidity burden, visit the health care system more frequently and thus have more complete data, compared with others. Ignoring such dependence of exposure and outcome misclassification on visit frequency can bias estimates of associations in EHR analysis. We developed a framework for describing the structure of outcome and exposure misclassification due to informative visit processes in EHR data and assessed the utility of a quantitative bias analysis approach to adjusting for bias induced by informative visit patterns. Using simulations, we found that this method produced unbiased estimates across all informative visit structures, if the phenotype sensitivity and specificity were correctly specified. We applied this method in an example where the association between diabetes and progression-free survival in metastatic breast cancer patients may be subject to informative presence bias. The quantitative bias analysis approach allowed us to evaluate robustness of results to informative presence bias and indicated that findings were unlikely to change across a range of plausible values for phenotype sensitivity and specificity. Researchers using EHR data should carefully consider the informative visit structure reflected in their data and use appropriate approaches such as the quantitative bias analysis approach described here to evaluate robustness of study findings.
Long-term Impact of Tropical Cyclones on Disease Exacerbation Among Children with Asthma in the Eastern United States, 2000–2018
Authors: Weinberger Kate R. , Veeravalli Nina , Wu Xiao , Nassikas Nicholas J. , Spangler Keith R. , Joyce Nina R. , Wellenius Gregory A.
Published: April 2024

Background:

Tropical cyclones are associated with acute increases in mortality and morbidity, but few studies have examined their longer-term health consequences. We assessed whether tropical cyclones are associated with a higher frequency of symptom exacerbation among children with asthma in the following 12 months in eastern United States counties, 2000–2018.

Methods:

We defined exposure to tropical cyclones as a maximum sustained windspeed >21 meters/second at the county center and used coarsened exact matching to match each exposed county to one or more unexposed counties. We used longitudinal, de-identified administrative claims data to estimate the county-level, monthly risk of experiencing at least one asthma exacerbation requiring medical attention among commercially insured children aged 5–17 with prior diagnosis of asthma. We used a difference-in-differences approach implemented via a Poisson fixed effects model to compare the risk of asthma exacerbation in the 12 months before versus after each storm in exposed versus unexposed counties.

Results:

Across 43 tropical cyclones impacting the eastern United States, we did not observe evidence of an increase in the risk of symptom exacerbation in the 12 months following the storm (random-effects meta-analytic summary estimate: risk ratio = 1.03 [95% confidence interval = 0.96, 1.10], I
2 = 17%). However, certain storms, such as Hurricane Sandy, were associated with a higher risk of symptom exacerbation.

Conclusions:

These findings are consistent with the hypothesis that some tropical cyclones are detrimental to children’s respiratory health. However, tropical cyclones were not associated in aggregate with long-term exacerbation of clinically apparent asthma symptoms among a population of children with commercial health insurance.