bluuebunny/crossref_metadata_2025 huggingface dataset:
Response to Pralsetinib in Multi-Drug-Resistant Breast Cancer With CCDC6-RET Mutation
Authors: Zhao Jing , Xu Wei , Zhuo Xiaoli , Liu Lei , Zhang Junlei , Jiang Fengxian , Shen Yanru , Lei Yan , Hou Dongsheng , Lin Xiaoyan , Wang Cuiyan , Fu Guobin
Published: May 2023

Triple-negative breast cancers (TNBC) represent a pathological subtype of breast cancer, which are characterized by strong invasiveness, high metastasis rate, low survival rate, and poor prognosis, especially in patients who have developed resistance to multiline treatments. Here, we present a female patient with advanced TNBC who progressed despite multiple lines of treatments; next-generation sequencing (NGS) was used to find drug mutation targets, which revealed a coiled-coil domain-containing protein 6 (CCDC6)-rearranged during transfection (RET) gene fusion mutation. The patient was then given pralsetinib, and after one treatment cycle, a CT scan revealed partial remission and adequate tolerance to therapy. Pralsetinib (BLU-667) is a RET-selective protein tyrosine kinase inhibitor that can inhibit the phosphorylation of RET and downstream molecules as well as the proliferation of cells expressing RET gene mutations. This is the first case in the literature of metastatic TNBC with CCDC6-RET fusion treated with pralsetinib, an RET-specific antagonist. This case demonstrates the potential efficacy of pralsetinib in cases of TNBC with RET fusion mutations and suggests that NGS may reveal new opportunities and bring new therapeutic interventions to patients with refractory TNBC.
Juvenile Northern Spotted Owls with higher mass and intermediate levels of corticosterone have greater long-term survival
Authors: Mikkelsen Ashlee J , Lesmeister Damon B , O’Reilly Kathleen M , Dugger Katie M
Published: May 2023

Early life experiences have carry-over effects that manifest in later life stages. Challenging rearing environments result in more energy invested in immediate survival and less energy on growth and maturation, which can decrease survival in both the short- and long-term. One way to measure differences in energy allocation to growth between individuals is through physiological indices, such as concentrations of the metabolic hormone corticosterone, and body condition. Corticosterone increases in response to challenges to homeostasis and mobilizes stored fat and muscle to meet energetic demands. Maintaining elevated corticosterone can result in poor body condition and decreased survival. Juvenile or pre-breeding age classes are typically a substantial portion of the total population and serve key functions in population dynamics in many long-lived species. Thus, understanding how the rearing environment may influence demographics across life-history stages is crucial to understanding larger population dynamics. Yet, demographic models and conservation planning often lack vital rate estimates for early life stages because, prior to breeding, animals cannot be effectively sampled (i.e., they are unobservable). We used corticosterone concentrations in feathers and body mass of fledged juvenile Northern Spotted Owls (Strix occidentalis caurina) as indicators of potential energetic limitations early in life and used a multi-state modeling framework to quantify the effect of these indicators on apparent annual survival prior to claiming a territory (pre-territorial birds) and the probability of recruiting into the territorial population. Apparent annual survival for pre-territorial birds was higher for birds with greater mass, earlier banding dates, and intermediate levels of corticosterone. Birds with greater mass at banding were also more likely to recruit into the territorial population. Our results demonstrate the importance of early development and traditionally excluded life-history stages on long-term demographics. Although early life stages are difficult to observe, monitoring and conservation efforts may be improved by increasing studies on pre-territorial animals, control of Barred Owls, and conservation of forest structures important for Spotted Owls. This may contribute to increased juvenile survival and recruitment.
Phylogenomic analysis confirms the relationships among toucans, toucan-barbets, and New World barbets but reveals paraphyly of Selenidera toucanets and evidence for mitonuclear discordance
Authors: Ostrow Emily N , Catanach Therese A , Bates John M , Aleixo Alexandre , Weckstein Jason D
Published: May 2023

We reconstruct the species-level phylogenetic relationship among toucans, toucan-barbets, New World barbets using phylogenomic data to assess the monophyly and relationships at the family, generic, and specific levels. Our analyses confirmed (1) the monophyly of toucans (Aves: Ramphastidae), toucan-barbets (Aves: Semnornithidae), and New World barbets (Aves: Capitonidae) and that the toucan-barbets are sister to the toucans, an arrangement suggested, but poorly supported, in previously published phylogenies; (2) the paraphyly of lowland Selenidera toucanets with respect to Andigena mountain-toucans; and (3) evidence of some mitonuclear discordance, suggesting introgression or incomplete lineage sorting. For example, mitonuclear conflict in the phylogenetic placement of Ramphastos vitellinus subspecies suggests that Amazonian populations of Ramphastos vitellinus ariel may have introgressed mitogenomes derived from other Amazonian vitellinus taxa. To reconstruct the phylogenetic history of toucans, toucan-barbets, and New World barbets, we included all species-level taxa from the three families, with the addition of outgroups from the two major clades of Old World barbets (Megalaimidae and Lybiidae). We analyzed a combination of UCE sequences and whole mitochondrial genome sequences to reconstruct phylogenetic trees.
Medical cannabis in schools: The experiences of caregivers
Authors: Mansell Holly , Zaslawski Zina , Mbabaali Sophia , King Patricia M , Kelly Lauren E , Lougheed Taylor , Anderson Jennifer , Huntsman Richard J , Alcorn Jane
Published: May 2023

Objectives

Implementing medical cannabis (MC) into a child’s daily routine can be challenging and there is a lack of guidance for its therapeutic use in schools in Canada. Our objective was to learn about the experiences of caregivers of school-aged children who require MC.

Methods

Qualitative description was used and caregivers were interviewed about MC in schools and in general. The transcripts were entered into Dedoose software for qualitative analysis and content analysis was performed. Sentences and statements were ascribed line by line into meaning units and labelled with codes, and organized according to categories and subcategories.

Results

Twelve caregivers of school-aged children who take MC participated. The most common reasons for treatment were drug-resistant epilepsy (DRE), autism, or other developmental disorders. Approximately half of the participants’ children (n = 6) took MC during the school day and most (5/6) perceived their experiences to be positive or neutral but reported a lack of knowledge about MC. While data saturation was not reached regarding MC in schools, rich dialogues were garnered about MC in general and three categories were identified: challenges (subcategories stigma, finding an authorizer, cost, dosing, and supply); parents as advocates (subcategories required knowledge, attitudes, skills, and sources of information); and caregiver relief for positive outcomes.

Conclusions

Caregivers demonstrate remarkable tenacity despite the many challenges associated with MC use. Education and practice change are needed to ensure that children using MC can benefit from or continue to experience its positive outcomes within the school environment and beyond.
Taking Risks to Protect Others—Pediatric Vaccination and Moral Responsibility
Authors: Nihlén Fahlquist Jessica
Published: May 2023

The COVID-19 pandemic during 2020–2022 raised ethical questions concerning the balance between individual autonomy and the protection of the population, vulnerable individuals and the healthcare system. Pediatric COVID-19 vaccination differs from, for example, measles vaccination in that children were not as severely affected. The main question concerning pediatric vaccination has been whether the autonomy of parents outweighs the protection of the population. When children are seen as mature enough to be granted autonomy, questions arise about whether they have the right to decline vaccination and who should make the decision when parents disagree with each other and/or the child. In this paper, I argue that children should be encouraged to not only take responsibility for themselves, but for others. The discussion of pediatric vaccination in cases where this kind of risk–benefit ratio exists extends beyond the 2020–2022 pandemic. The pandemic entailed a question that is crucial for the future of public health as a global problem, that is, to what extent children should be seen as responsible decision-makers who are capable of contributing to its management and potential solution. I conclude that society should encourage children to cultivate such responsibility, conceived as a virtue, in the context of public health.
Peroxidase proximity selection to identify aptamers targeting a subcellular location
Authors: Wilbanks Brandon , Beimers William , Dugan Maria , Weiskittel Taylor , Maher L J
Published: May 2023

The efficient and specific delivery of functional cargos such as small-molecule drugs, proteins, or nucleic acids across lipid membranes and into subcellular compartments is a significant unmet need in nanomedicine and molecular biology. Systematic Evolution of Ligands by EXponential enrichment (SELEX) exploits vast combinatorial nucleic acid libraries to identify short, nonimmunogenic single-stranded DNA molecules (aptamers) capable of recognizing specific targets based on their 3D structures and molecular interactions. While SELEX has previously been applied to identify aptamers that bind specific cell types or gain cellular uptake, selection of aptamers capable of carrying cargos to specific subcellular compartments is challenging. Here, we describe peroxidase proximity selection (PPS), a generalizable subcellular SELEX approach. We implement local expression of engineered ascorbate peroxidase APEX2 to biotinylate naked DNA aptamers capable of gaining access to the cytoplasm of living cells without assistance. We discovered DNA aptamers that are preferentially taken up into endosomes by macropinocytosis, with a fraction apparently accessing APEX2 in the cytoplasm. One of these selected aptamers is capable of endosomal delivery of an IgG antibody.
Reference Points Spillovers: Micro-Level Evidence from Real Estate
Authors: Giacoletti Marco , Parsons Christopher A
Published: May 2023

Homeowners who originally bought when marketwide price levels were high (low) fetch high (low) sales prices and rents, even decades later. We study the propagation of reference-dependence to neighboring listings. The “spillover” reference point effect is about one-half as large as the “own” reference point effect. Neither house quality nor location appears capable of explaining the result. Using a simple model to provide empirical predictions, we find support for a competition-based mechanism. We quantify the aggregate effect of own and spillover reference point effects on aggregate prices and/or rents at the ZIP code level.

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Measuring the Expected Effects of the Global Tax Reform
Authors: Gómez-Cram Roberto , Olbert Marcel
Published: May 2023

Over 140 countries agreed on a fundamental corporate tax reform in 2021 to be implemented in 2023 and beyond. To measure its potential effects, we study asset price changes within minutes of the reform announcements. We construct proxies for the reform’s costs regarding U.S. companies’ tax burdens and countries’ public finances. Likely exposed companies exhibit significant negative stock returns. Our lower-bound estimates indicate total shareholder value losses of $112.6 billion one day after the reform announcements. Further, likely exposed countries experience increases in sovereign debt credit risk. Our findings inform the cost-benefit analysis of a historical international tax reform.

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Deciphering locomotion in reptiles: application of elliptic Fourier transforms to femoral microanatomy
Authors: Gônet Jordan , Bardin Jérémie , Girondot Marc , Hutchinson John R , Laurin Michel
Published: May 2023

Reptiles represent one of the most diverse groups of tetrapod vertebrates. Extant representatives of reptiles include lepidosaurs (lizards), testudines (turtles) and archosaurs (crocodiles and birds). In particular, they show an important locomotor diversity with bipedal, quadrupedal and facultatively bipedal taxa. This diversity is accompanied by substantial microanatomical disparity in the limb bones. Although many studies have highlighted the link between locomotion and bone microstructure, the latter has never been quantitatively studied from an angular perspective. Indeed, some taxa show microanatomical heterogeneity in cross-section. Here we show, using elliptic Fourier transforms and statistical analyses integrating phylogeny, how angular microanatomical parameters measured on reptilian femoral cross-sections, such as angular bone compactness, can be related to locomotion in this clade. Although phylogeny appears to have a significant impact on our results, we show that a functional signal exists. In particular, we show that bipeds and quadrupeds present a craniolateral-caudomedial and dorsoventral deficit in bone compactness, respectively. This reflects cross-sectional eccentricity in these directions that we relate to the forces acting upon the femur in different postural contexts. This work contributes to deciphering the complex interplay between phylogeny, femoral cross-sectional microanatomy and locomotion in reptiles.
Involvement of the Cell Wall–Integrity Pathway in Signal Recognition, Cell-Wall Biosynthesis, and Virulence inMagnaporthe oryzae
Authors: Lu Kailun , Chen Rangrang , Yang Yi , Xu Hui , Jiang Jihong , Li Lianwei
Published: May 2023

The fungal cell wall is the first layer exposed to the external environment. The cell wall has key roles in regulating cell functions, such as cellular stability, permeability, and protection against stress. Understanding the structure of the cell wall and the mechanism of its biogenesis is important for the study of fungi. Highly conserved in fungi, including Magnaporthe oryzae, the cell wall–integrity (CWI) pathway is the primary signaling cascade regulating cell-wall structure and function. The CWI pathway has been demonstrated to correlate with pathogenicity in many phytopathogenic fungi. In the synthesis of the cell wall, the CWI pathway cooperates with multiple signaling pathways to regulate cell morphogenesis and secondary metabolism. Many questions have arisen regarding the cooperation of different signaling pathways with the CWI pathway in regulating cell-wall synthesis and pathogenicity. In this review, we summarized the latest advances in the M. oryzae CWI pathway and cell-wall structure. We discussed the CWI pathway components and their involvement in different aspects, such as virulence factors, the possibility of the pathway as a target for antifungal therapies, and crosstalk with other signaling pathways. This information will aid in better understanding the universal functions of the CWI pathway in regulating cell-wall synthesis and pathogenicity in M. oryzae.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Spinal Pial Arteriovenous Fistulas: Angioarchitecture and Management
Authors: Mollica Caterina , Bonasia Sara , Marchi Francesco , Robert Thomas
Published: May 2023

Spinal pial arteriovenous fistulas (spAVFs) are rare, high-flow vascular malformations consisting of a single dilated pial artery connecting directly to an enlarged draining vein. This article describes the anatomic, clinical, and diagnostic features of spAVFs, to help clinicians to select the best treatment option. Both surgical and endovascular treatments are effective; microsurgery has a higher success rate. To maximize the exclusion rate, a multidisciplinary approach and adequate preoperative study are mandatory.
Patient Perspectives Regarding Clinician Communication During Telemedicine Compared With In-Clinic Abortion
Authors: Godfrey Emily M. , Fiastro Anna E. , Ruben Molly R. , Young Elizabeth V. , Bennett Ian M. , Jacob-Files Elizabeth
Published: May 2023

OBJECTIVE:

To explore patient perspectives regarding patient–clinician communication during telemedicine medication abortion compared with traditional, facility based, in-clinic visits.

METHODS:

We conducted semi-structured interviews with participants who received either live, face-to-face telemedicine or in-clinic medication abortion from a large, reproductive health care facility in Washington State. Using Miller's conceptual framework for patient–doctor communication in telemedicine settings, we developed questions exploring participants' experiences of the medication abortion consultation, including the clinician's verbal and nonverbal interpersonal approach and communication of relevant medical information, and the setting where care was received. We used inductive-deductive constant comparative analysis to identify major themes. We summarize patient perspectives using patient–clinician communication terms outlined in Dennis' quality abortion care indicator list.

RESULTS:

Thirty participants completed interviews (aged 20–38 years), 20 of whom had medication abortion by telemedicine and 10 who received in-clinic services. Participants who received telemedicine abortion services reported high-quality patient–clinician communication, which came from their freedom to choose their consultation location, and reported feeling more relaxed during clinical encounters. In contrast, most in-clinic participants portrayed their consultations as lengthy, chaotic, and lacking comfort. In all other domains, both telemedicine and in-clinic participants reported similar levels of interpersonal connection to their clinicians. Both groups appreciated medical information about how to take the abortion pills and relied heavily on clinic-based printed materials and independent online resources to answer questions during the at-home termination process. Both telemedicine and in-clinic participant groups were highly satisfied with their care.

CONCLUSION:

Patient-centered communication skills used by clinicians during facility based, in-clinic care translated well to the telemedicine setting. However, we found that patients who received medication abortion through telemedicine favorably ranked their patient–clinician communication overall as compared with those in traditional, in-clinic settings. In this way, telemedicine abortion appears to be a beneficial patient-centered approach to this critical reproductive health service.
Evaluation of Digital Health Strategy to Support Clinician-Led Critically Ill Patient Population Management: A Randomized Crossover Study
Authors: Herasevich Svetlana , Pinevich Yuliya , Lipatov Kirill , Barwise Amelia K. , Lindroth Heidi L. , LeMahieu Allison M. , Dong Yue , Herasevich Vitaly , Pickering Brian W.
Published: May 2023

OBJECTIVES:

To investigate whether a novel acute care multipatient viewer (AMP), created with an understanding of clinician information and process requirements, could reduce time to clinical decision-making among clinicians caring for populations of acutely ill patients compared with a widely used commercial electronic medical record (EMR).

DESIGN:

Single center randomized crossover study.

SETTING:

Quaternary care academic hospital.

SUBJECTS:

Attending and in-training critical care physicians, and advanced practice providers.

INTERVENTIONS:

AMP.

MEASUREMENTS AND MAIN RESULTS:

We compared ICU clinician performance in structured clinical task completion using two electronic environments—the standard commercial EMR (Epic) versus the novel AMP in addition to Epic. Twenty subjects (10 pairs of clinicians) participated in the study. During the study session, each participant completed the tasks on two ICUs (7–10 beds each) and eight individual patients. The adjusted time for assessment of the entire ICU and the adjusted total time to task completion were significantly lower using AMP versus standard commercial EMR (–6.11; 95% CI, –7.91 to –4.30 min and –5.38; 95% CI, –7.56 to –3.20 min, respectively; p < 0.001). The adjusted time for assessment of individual patients was similar using both the EMR and AMP (0.73; 95% CI, –0.09 to 1.54 min; p = 0.078). AMP was associated with a significantly lower adjusted task load (National Aeronautics and Space Administration-Task Load Index) among clinicians performing the task versus the standard EMR (22.6; 95% CI, –32.7 to –12.4 points; p < 0.001). There was no statistically significant difference in adjusted total errors when comparing the two environments (0.68; 95% CI, 0.36–1.30; p = 0.078).

CONCLUSIONS:

When compared with the standard EMR, AMP significantly reduced time to assessment of an entire ICU, total time to clinical task completion, and clinician task load. Additional research is needed to assess the clinicians’ performance while using AMP in the live ICU setting.
Comparative evaluation of urolithiasis management options in patients with horseshoe kidney: A systematic review and meta-analysis
Authors: Qaoud Yazan , Al Tali Merella , Boland Fiona , Simpson Andrew , Davis Niall
Published: May 2023

Background

Horseshoe kidney is a rare congenital anomaly commonly complicated by urolithiasis. Extracorporeal shockwave lithotripsy (ESWL), ureteroscopy (URS), and percutaneous nephrolithotomy (PCNL) are treatment options for horseshoe kidney stones. The aim of this systematic review is to compare the benefits and risks of these management options.

Methods

MEDLINE, EMBASE, and Cochrane Library databases were searched from inception to February 2022. A total of 516 nonduplicate studies were screened against the inclusion and exclusion criteria. Studies comparing at least 2 interventions with ≥10 patients per intervention were included.

Results

Nine retrospective observational studies published from 2007 to 2021 with a total of 565 patients were included. Reported mean ± SD or mean (range) stone sizes ranged between 17.90 ± 2.43 mm and 27.9 ± 8.6 mm for PCNL, 8.4 (2–25) mm and 22.3 ± 9.1 mm for URS, and 11.9 ± 2.0 mm and 16.8 ± 4.4 mm for ESWL. There was no difference in single-session and overall stone-free rate (SFR) between PCNL and URS, with a risk ratio of 1.04 (95% confidence interval, 0.95–1.13; I
2 = 20.63%). Ureteroscopy had better stone clearance than ESWL, with an overall SFR risk ratio of 1.38 (95% confidence interval, 1.04–1.82; I
2 = 0%). There was no statistically significant difference in overall SFR between PCNL and ESWL. Most patients who underwent URS and ESWL experienced Clavien-Dindo (CD) grade I-II complications. Percutaneous nephrolithotomy was associated with the highest complication rates, including 5 CD grade III and 3 CD grade IV complications and a mean postoperative hemoglobin drop of 0.47 to 1.83 g/dL. There were no CD grade V complications across all studies.

Conclusions

There was no difference in SFR between PCNL and URS. Ureteroscopy was associated with a smaller stone burden and fewer and less severe complications. Ureteroscopy was found to be more effective than ESWL with a higher SFR and comparable safety profile. Further large-scale randomized controlled trials are needed to confirm these findings.
Enfortumab vedotin and pembrolizumab as monotherapies and combination treatment in locally advanced or metastatic urothelial carcinoma: A narrative review
Authors: Bantounou Maria A. , Plascevic Josip , MacDonald Lewis , Wong Man Chun , O'Connell Neasa , Galley Helen F.
Published: May 2023

Background

Bladder cancer is the 10th most common cancer globally. The majority of bladder cancers are urothelial carcinomas (UCs), which, if locally advanced or metastatic, carry poor long-term prognosis. Cancer cells can evade the immune system by expressing the programmed cell death ligand 1 protein (PD-L1). Programmed cell death ligand 1 protein binds to programmed cell death protein 1 (PD-1) on T cells, inhibiting their antitumor action. Bladder tumor cells also overexpress nectin-4, a cell adhesion polypeptide that contributes to metastasis, worsening prognosis. Current platinum-based chemotherapy treatments are suboptimal. This review aimed to assess novel treatments for locally advanced or metastatic UC that specifically target PD-L1 or nectin-4, namely, the PD-1 inhibitor pembrolizumab and the anti–nectin-4 antibody-drug conjugate enfortumab vedotin (EV).

Materials and methods

Relevant English-language peer-reviewed articles and conference abstracts from the last 5 years were identified through MEDLINE and EMBASE database searches. A narrative review was performed, with key results outlined below.

Results

Pembrolizumab was demonstrated to be superior to chemotherapy as a second-line treatment for platinum-unresponsive participants in the KEYNOTE-045 trial, resulting in its Food and Drug Administration (FDA) approval. Enfortumab vedotin therapy resulted in superior outcomes compared with chemotherapy in the EV-301 trial, resulting in FDA approval for its use for patients with locally advanced or metastatic UC who had previously undergone treatment with platinum-based chemotherapy and PD-1/PD-L1 inhibitors. Positive preliminary results for pembrolizumab and EV combination therapy have led to FDA approval in patients with locally advanced or metastatic UC who are not eligible for platinum chemotherapy.

Conclusions

Pembrolizumab and EV represent novel treatment options for patients with locally advanced or metastatic UC with documented superior outcomes and tolerability as compared with standard chemotherapy.
Outcomes following liver transplant for alcohol-associated liver disease: comparing alcohol-associated hepatitis and cirrhosis
Authors: Schroeder Matthew , Pedersen Mark , Petrasek Jan , Grant Lafaine
Published: May 2023

Background:

Liver transplant (LT) is a highly effective therapy for refractory severe alcohol-associated hepatitis (SAH), but optimal selection criteria remain unknown. We aim to evaluate the outcomes of patients who received LT for alcohol-associated liver disease at our center following the introduction of updated selection criteria, including the removal of the minimum sobriety requirement.

Methods:

Data were collected on all patients who underwent LT for alcohol-associated liver disease from January 1, 2018, to September 30, 2020. Patients were divided into SAH and cirrhosis cohorts based on disease phenotype.

Results:

One hundred twenty-three patients underwent LT for alcohol-associated liver disease, including 89 (72.4%) for cirrhosis and 34 (27.6%) for SAH. There was no difference in 1- (97.1 ± 2.9% vs. 97.7 ± 1.6%, p = 0.97) and 3-year (97.1 ± 2.9% vs. 92.4 ± 3.4%, p = 0.97) survival between SAH and cirrhosis cohorts. Return to alcohol use was more frequent in the SAH cohort at 1 year (29.4 ± 7.8% vs. 11.4 ± 3.4%, p = 0.005) and 3 years (45.1 ± 8.7% vs. 21.0 ± 6.2%, p = 0.005) including higher frequencies of both slips and problematic drinking. Unsuccessful alcohol use counseling (HR 3.42, 95% CI 1.12–10.5) and prior alcohol support meetings (HR 3.01, 95% CI 1.03–8.83) predicted a return to harmful alcohol use patterns in early LT recipients. Both duration of sobriety (c-statistic 0.32 (95% CI 0.34-0.43) and SALT score (c-statistic 0.47, 95% CI 0.34–0.60) were independently poor predictors of return to harmful drinking.

Conclusion:

Survival following LT was excellent in both SAH and cirrhosis cohorts. Higher rates of return to alcohol use highlight the importance of further individualized refinement of selection criteria and improved support following LT.
Clinical trials reimagined
Authors: Kwo Paul Y. , Patel Tushar
Published: May 2023

Clinical trials have been a central driver of change and have provided the evidence base necessary to advance new therapies for liver diseases. This review provides a perspective on the status of trials in hepatology and a vantage point into the emerging capabilities and external forces that will shape the conduct of clinical trials in the future. The adaptations to clinical trial operations in response to the disruptions by the COVID-19 pandemic and opportunities for innovation in hepatology trials are emphasized. Future trials in hepatology will be driven by unmet therapeutic needs and fueled by technological advances incorporating digital capabilities with expanded participant-derived data collection, computing, and analytics. Their design will embrace innovative trial designs adapted to these advances and that emphasize broader and more inclusive participant engagement. Their conduct will be further shaped by evolving regulatory needs and the emergence of new stakeholders in the clinical trials ecosystem. The evolution of clinical trials will offer unique opportunities to advance new therapeutics that will ultimately improve the lives of patients with liver diseases.
Development and Implementation of an Academic and Professional Nursing Organization Partnership to Enhance Leadership Skills and Knowledge About HIV-Related Nursing Care Among Diverse, Prelicensure, Clinical Nurse Leader Scholars
Authors: Fahie Vanessa P. , Chen Lynn , Lemaire Gail Schoen , Ahmed Hina S.
Published: May 2023

Historically, racial discrimination, few role models, and a general lack of support both in academic and professional contexts has hindered the education and career advancement of minority nursing students. The American Association of Colleges of Nursing (AACN), in its Guiding Principles for Academic-Practice Partnerships, describes the creation of an academic–professional nursing organization partnership to address barriers to the success of nursing students from underrepresented groups. In keeping with the AACN's guiding principles, the University of Maryland School of Nursing and the Association of Nurses in AIDS Care (ANAC) developed a partnership to deliver a multifaceted program for prelicensure, second-degree, Master of Science in Nursing, Clinical Nurse Leader Scholars which prepares them to address the health care needs of people living with HIV/AIDS and bolsters student leadership knowledge and skills. The objective of this article is to describe the program components, outcomes, and lessons learned from this academic–professional nursing organization partnership. The approach described may be useful for future partnerships designed to enhance leadership experiences and skills for minority nursing students and will hopefully be used to advocate for their success.
Telehealth policy guide for nurse practitioners: A compliance checklist
Authors: Kobeissi Mahrokh M.
Published: May 2023

Telehealth expanded health care delivery since the start of the COVID-19 public health emergency (PHE). In early 2020, emergency declarations and subsequent policy changes resulted in telehealth flexibilities to support health care providers limit the spread of disease and maintain access to health services. Pandemic policies affected provider licensing requirements, cross-state practice, telemedicine modality, prescribing rules, privacy and security discretions, and reimbursement. On January 30, 2023, the Biden Administration announced it would end the PHE on May 11, 2023, which means some telehealth flexibilities in effect since 2020 will expire at various times through December 31, 2024, in the absence of permanent legislation. It can be challenging for nurse practitioners (NPs) to remain up to date on telehealth rules and regulations in a changing regulatory environment. The purpose of this article is to discuss telehealth policy and propose a checklist, developed specifically for NPs, to guide compliance with federal and state laws. Nurse practitioners using telehealth must work within their scope of practice and follow discipline-specific guidance to avoid potential malpractice.
Type of donor liver transplant does not affect pregnancy outcomes—a systematic review and meta-analysis
Authors: Osman Karim T. , Nayfeh Tarek , Alrukby Judy , Mehta Neev , Elkhabiry Lina , Spencer Carol , Aby Elizabeth S.
Published: May 2023

Liver transplant (LT) has become increasingly common among reproductive-aged women. The effect of the type of liver donor, either a living donor LT (LDLT) or a deceased donor LT, on pregnancy outcomes is unknown. As such, we aim to review the available literature and assess obstetric, pregnancy, or delivery outcomes in LDLT. We conducted a comprehensive literature review of MEDLINE, EMBASE, Cochrane, and Scopus databases. Random-effect meta-regression assessed the association between the percentage of women who underwent LDLT (independent variable) and the proportion of outcomes. Meta-regression results were expressed as a regression coefficient, which transforms the proportion of outcomes of interest associated with a 1% increase in the percentage of LDLT patients. A value of 0 denotes no relationship between the outcomes and LDLT. A total of 6 articles (438 patients) were included, with a total of 806 pregnancies. Eighty-eight (20.09%) patients underwent LDLT. None of the studies segregated the data based on the type of donor LT. The median time from LT to pregnancy was 4.86 (4.62–5.03) years. Twelve (1.5%) stillbirths were reported. LDLT was statistically significantly associated with a higher rate of stillbirths (coefficient 0.002, p < 0.001; I2 0%). The type of donor LT was not associated with an increased risk of other obstetric, pregnancy, or delivery complications. This is the first meta-analysis to evaluate the effect of the type of donor LT on pregnancy outcomes. This study highlights the lack of robust literature addressing this important topic. The results suggest that pregnancy outcomes after LDLT and deceased donor LT are comparable. Despite LDLT being statistically significantly associated with a higher rate of stillbirths, the association is weak and is unlikely to be clinically significant.
Artificial intelligence using a deep learning versus expert computed tomography human reading in calcium score and coronary artery calcium data and reporting system classification
Authors: Aldana-Bitar Jairo , Cho Geoffrey W. , Anderson Lauren , Karlsberg Daniel W. , Manubolu Venkat S. , Verghese Dhiran , Hussein Luay , Budoff Matthew J. , Karlsberg Ronald P.
Published: May 2023

Background

Artificial intelligence (AI) applied to cardiac imaging may provide improved processing, reading precision and advantages of automation. Coronary artery calcium (CAC) score testing is a standard stratification tool that is rapid and highly reproducible. We analyzed CAC results of 100 studies in order to determine the accuracy and correlation between the AI software (Coreline AVIEW, Seoul, South Korea) and expert level-3 computed tomography (CT) human CAC interpretation and its performance when coronary artery disease data and reporting system (coronary artery calcium data and reporting system) classification is applied.

Methods

A total of 100 non-contrast calcium score images were selected by blinded randomization and processed with the AI software versus human level-3 CT reading. The results were compared and the Pearson correlation index was calculated. The CAC-DRS classification system was applied, and the cause of category reclassification was determined using an anatomical qualitative description by the readers.

Results

The mean age was age 64.5 years, with 48% female. The absolute CAC scores between AI versus human reading demonstrated a highly significant correlation (Pearson coefficient R = 0.996); however, despite these minimal CAC score differences, 14% of the patients had their CAC-DRS category reclassified. The main source of reclassification was observed in CAC-DRS 0–1, where 13 were recategorized, particularly between studies having a CAC Agatston score of 0 versus 1. Qualitative description of the errors showed that the main cause of misclassification was AI underestimation of right coronary calcium, AI overestimation of right ventricle densities and human underestimation of right coronary artery calcium.

Conclusion

Correlation between AI and human values is excellent with absolute numbers. When the CAC-DRS classification system was adopted, there was a strong correlation in the respective categories. Misclassified were predominantly in the category of CAC = 0, most often with minimal values of calcium volume. Additional algorithm optimization with enhanced sensitivity and specificity for low values of calcium volume will be required to enhance AI CAC score utilization for minimal disease. Over a broad range of calcium scores, AI software for calcium scoring had an excellent correlation compared to human expert reading and in rare cases determined calcium missed by human interpretation.
What is the most appropriate follow-up time for detecting the epidemiological relationship between coronary artery disease and its main risk factors: novel findings from a 35-year follow-up study
Authors: Voutilainen Ari , Brester Christina , Kolehmainen Mikko , Tuomainen Tomi-Pekka
Published: May 2023

Background

The aim was to investigate the most appropriate follow-up time to detect the associations of coronary artery disease (CAD) with its traditional risk factors in a long-term prospective cohort study.

Methods

The Kuopio Ischaemic Heart Disease Risk Factors Study provided the study material of 1958 middle-aged men free from CAD at baseline and followed up for 35 years. We performed Cox models adjusted for age, family history, diabetes, obesity, hypercholesterolemia, hypertension, smoking, and physical activity, investigated covariate interactions, and tested Schoenfeld residuals to detect time-dependent covariates. Moreover, we applied a sliding window procedure with a subarray of 5 years to better differentiate between risk factors manifested within years and those manifested within decades. The investigated manifestations were CAD and fatal acute myocardial infarction (AMI).

Results

Seven hundred seventeen (36.6%) men had CAD, and 109 (5.6%) men died from AMI. After 10 years of follow-up, diabetes became the strongest predictor of CAD with a fully adjusted hazard ratio (HR) of 2.5–2.8. During the first 5 years, smoking was the strongest predictor (HR 3.0–3.8). When the follow-up time was 8–19 years, hypercholesterolemia predicted CAD with a HR of >2. The associations of CAD with age and diabetes depended on time. Age hypertension was the only statistically significant covariate interaction. The sliding window procedure highlighted the significance of diabetes over the first 20 years and hypertension after that. Regarding AMI, smoking was associated with the highest fully adjusted HR (2.9–10.1) during the first 13 years. The associations of extreme and low physical activity with AMI peaked when the follow-up time was 3–8 years. Diabetes showed its highest HR (2.7–3.7) when the follow-up time was 10–20 years. During the last 16 years, hypertension was the strongest predictor of AMI (HR 3.1–6.4).

Conclusion

The most appropriate follow-up time for most CAD risk factors was 10–20 years. Concerning smoking and hypertension shorter and longer follow-up times could be considered, respectively, particularly when studying fatal AMI. In general, prospective cohort studies of CAD would provide more comprehensive results by reporting point estimates in relation to more than one timepoint and concerning sliding windows.
Telemedicine and home monitoring for COPD – a narrative review of recent literature
Authors: Poberezhets Vitalii , Kasteleyn Marise J.
Published: May 2023

Purpose of review

Home monitoring is one of the methods of using telemedical technologies aimed to provide care at home and maintain a connection between patients and healthcare providers. The purpose of this review is to describe recent advancements in the use of home monitoring for the care and management of chronic obstructive pulmonary disease (COPD) patients.

Recent findings

Recent studies focused on remote monitoring for patients with COPD proved the positive effect of home monitoring interventions on the frequency of exacerbations and unscheduled healthcare visits, duration of patients’ physical activity, proved sensitivity and overall specificity of such interventions and highlighted the effectiveness of self-management.

Assessing end-user experience revealed high satisfaction levels among patients and healthcare staff who used home monitoring interventions. The majority of physicians and staff responded positively about the interventions’ facilitation of communication with patients. Moreover, healthcare staff considered such technologies useful for their practice.

Home monitoring for COPD patients improves medical care and disease management despite minor drawbacks and obstacles to its wide implementation. Involving end-users in evaluating and co-creating new telemonitoring interventions has the potential to improve the quality of remote monitoring for COPD patients in the near future.
Retrograde intra renal surgery and safety: pressure and temperature. A systematic review
Authors: Panthier Frédéric , Pauchard Felipe , Traxer Olivier
Published: May 2023

Purpose of review

Retrograde intra renal surgery (RIRS) with laser lithotripsy represents the gold-standard to treat renal stones up to 20 mm. Controlling intraoperative parameters such as intrarenal pressure (IRP) and temperature (IRT) is mandatory to avoid complications. This article reviews advances in IRP and IRT over the last 2 years.

Recent findings

We conducted a PubMed/Embase search and reviewed publications that include temperature and pressure during RIRS. Thirty-four articles have been published which met the inclusion criteria. Regarding IRP, a consensus has emerged to control IRP during RIRS, in order to avoid (barotraumatic and septic) complications. Several monitoring devices are under evaluation but none of them are clinically approved for RIRS. Ureteral access sheath, low irrigation pressure and occupied working channel help to maintain a low IRP. Robotic systems and suction devices would improve IRP intraoperative management and monitoring. IRT determinants are the irrigation flow and laser settings. Low power settings(<20 W) with minimal irrigation flow (5–10 ml/min) are sufficient to maintain low IRT and allows continuous laser activation.

Recent evidence suggests that IRP and IRT are closely related. IRP depends on inflow and outflow rates. Continuous monitoring would help to avoid surgical and infectious complications. IRT depends on the laser settings and the irrigation flow.
Fracture healing—orthobiologics: from basic science to clinical application
Authors: Johnson Joey P. , Ahn Jaimo , Dirschl Douglas R. , Wixted John J. , Evans Andrew R.
Published: May 2023

Orthopaedics as a field and a profession is fundamentally concerned with the treatment of musculoskeletal disease, in all of its many forms. Our collective understanding of the cellular mechanisms underlying musculoskeletal pathology resulting from injury continues to evolve, opening novel opportunities to develop orthobiologic treatments to improve care. It is a long path to move from an understanding of cellular pathology to development of successful clinical treatment, and this article proposes to discuss some of the challenges to achieving translational therapies in orthopaedics. The article will focus on challenges that clinicians will likely face in seeking to bring promising treatments forward to clinical practice and strategies for improving success in translational efforts.
Gymnodinialimonas phycosphaerae sp. nov., a phycosphere bacterium isolated from Karlodinium veneficum
Authors: Peng Yuxin , Jiang Lingmin , Jiang Yue , Seo Jiyoon , Jeon Doeun , Kim Young-Min , Li Zhun , Lee Jiyoung
Published: May 2023

A facultative anaerobic, Gram-negative, non-motile, rod-shaped bacterial strain, designated N5T, was obtained from the phycosphere microbiota of the marine planktonic dinoflagellate, Karlodinium veneficum. Strain N5T showed growth on marine agar at 25 °C, pH 7 and 1 % (w/v) NaCl and produced a yellow colour. According to a phylogenetic study based on 16S rRNA gene sequences, strain N5T has a lineage within the genus

Gymnodinialimonas

. The G+C content in the genome of strain N5T is 62.9 mol% with a total length of 4 324 088 bp. The NCBI Prokaryotic Genome Annotation Pipeline revealed that the N5T genome contained 4230 protein-coding genes and 48 RNA genes, including a 5S rRNA, 16S rRNA, 23S rRNA, 42 tRNA, and three ncRNAs. Genome-based calculations (genome-to-genome distance, average nucleotide identity and DNA G+C content) clearly indicated that the isolate represents a novel species within the genus

Gymnodinialimonas

. The predominant fatty acids were C19 : 0 cyclo ω8c and feature 8 (comprising C18 : 1
ω6c and/or C18 : 1
ω7c). The major polar lipids were phosphatidylglycerol, phosphatidylethanolamine and phosphatidylcholine. The main respiratory quinone was Q-10. Based on its phenotypic, phylogenetic, genomic and chemotaxonomic features, strain N5T represents a novel species of the genus

Gymnodinialimonas

, for which the name Gymnodinialimonas phycosphaerae sp. nov. is proposed. The type strain is N5T (=KCTC 82362T=NBRC 114899T).
Biomolecular Condensates defined by Receptor Independent Activator of G protein Signaling: Properties and Regulation
Authors: Vural Ali , Lanier Stephen M.
Published: May 2023

Activator of G-protein Signaling 3 (AGS3), a receptor independent activator of G-protein signaling, oscillates among different subcellular compartments in a regulated manner including punctate entities referred to as biomolecular condensates (BMCs). The dynamics of the AGS3 oscillation and the specific subcompartment within the cell is intimately related to the functional diversity of the protein. To further address the properties and regulation of AGS3 BMCs, we asked initial questions regarding a) the distribution of AGS3 across the broader BMC landscape with and without cellular stress, and b) the core material properties of these punctate structures. Cellular stress (oxidative, pHi, thermal) induced the formation of AGS3 BMCs in two cell lines (Hela, COS7) as determined by fluorescent microscopy. The AGS3-BMCs generated in response to oxidative stress were distinct from stress granules (SG) as defined by the SG marker protein G3BP1 and RNA processing BMCs defined by the P-body protein Dcp1a. Immunoblots of fractionated cell lysates indicated that cellular stress shifted AGS3 to the membrane pellet fraction, whereas the protein markers for stress granules (G3BP1) SG- BMCs remained in the supernatant. We next asked if the formation of the stress-induced AGS3 BMCs was regulated by protein binding partners involved with signal processing. The stress-induced generation of AGS3 BMCs was regulated by the signaling protein Gαi3, but not by the AGS3 binding partner DVL2. Finally, we addressed the fluidity or rigidity of the stress-induced AGS3-BMCs using fluorescent recovery following photobleaching of individual AGS3-BMCs. The AGS3-BMCs indicated distinct diffusion kinetics that were consistent with restricted mobility of AGS3 within the stress-induced AGS3-BMCs. These data suggest that AGS3 BMCs represents a distinct class of stress granules that define a new type of BMC that may serve as previously unappreciated signal processing nodes.

Summary statement

AGS3 assembles into distinct biomolecular condensates in response to cell stress and this assembly is selectively regulated by AGS3 binding partners involved in signal transduction within the cell.