bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetic Consideration of Venetoclax in Acute Myeloid Leukemia Patients: A Potential Candidate for TDM? A Short Communication
Authors: Philippe Michael , Guitton Jérôme , Goutelle Sylvain , Thoma Yann , Favier Bertrand , Chtiba Nour , Michallet Mauricette , Belhabri Amine 
Published: November 2023

Background:
Venetoclax (VNX)-based regimens have demonstrated significantly favorable outcomes in patients with acute myeloid leukemia (AML) and are now becoming the standard treatment. Tyrosine kinase inhibitors are administered at a fixed dose, irrespective of body surface area or weight. For such orally targeted therapies, real-world data have highlighted a larger pharmacokinetic (PK) interindividual variability (IIV) than expected. Even if VNX PKs have been well characterized and described in the literature, only 1 clinical trial–based PK study has been conducted in patients with AML. This study aimed to evaluate the PK of VNX in AML patients.

Material and methods:
We retrospectively analyzed all patients treated with a combination of VNX–azacitidine between January and July 2022 at our center, using at least 1 available VNX blood sample. Based on a previously published population PK model, individual PK parameters were estimated to evaluate the exposure and IIV.

Results:
and Discussion. Twenty patients received VNX in combination with azacitidine, according to the PK data. A total of 93 plasma concentrations were collected. The dose of VNX was 400 mg, except in 7 patients who received concomitant posaconazole (VNX 70 mg). The patients' weight ranged from 49 kg to 108 kg (mean = 78 kg). Mean individual clearance was 13.5 ± 9.4 L/h with mean individual daily area under the concentration–time curves of 35.8 mg.h/L with significant IIV (coefficient of variation = 41.1%). Ten patients were still alive (8 in complete response), but all experienced at least 1 hematological toxicity of grade ≥ 3.

Conclusions:
Based on the observed large PK variability in the data from our real-world AML patients, the risk of drug interactions and the recommended fixed-dosage regimen of VNX therapeutic drug monitoring may be useful.
An online mind-body program improves mental health and quality of life in primary biliary cholangitis: A randomized controlled trial
Authors: Watt Makayla , Hyde Ashley , Johnson Emily , Wright Gail M. , Vander Well Shauna , Sadasivan Chikku , Lee-Baggley Dayna , Spence John C. , Mason Andrew , Ko Hin Hin , Tam Edward , Tandon Puneeta 
Published: November 2023

Background and Aims:People with primary biliary cholangitis (PBC) experience high rates of mental distress and fatigue despite standard of care therapy. We aimed to assess the impact of an online mind-body intervention on these symptoms.Methods:This 12-week RCT used sequential mixed-methods evaluation. Alongside standard of care, participants with primary biliary cholangitis were randomized to receive weekly countdown emails, or the intervention consisting of (i) a weekly 20–30 minute-mind-body follow-along video, (ii) weekly 5–10-minute psychology-based “managing chronic disease skills videos,” and (iii) 10-minute telephone check-ins. The primary outcome was a change in the Hospital Anxiety and Depression Scale (HADS). Secondary outcomes evaluated changes in fatigue, perceived stress, resilience, and health-related quality of life. ANCOVA determined between-group differences.Results:Of the 87 randomized patients (control group: n = 44, intervention group: n = 43), the between-group HADS total score improved by 20.0% (95% CI 4.7, 35.2,p= 0.011). Significant improvements were seen in depression (25.8%), perceived stress (15.2%), and 2 primary biliary cholangitis-40 domains [emotional symptoms (16.3%) and social symptoms (11.8%)] with a mean satisfaction of 82/100. This corresponded with end-of-study qualitative findings. Although no improvements were observed in fatigue in the main analysis, a significant benefit was observed in the subgroup of intervention participants (20/36;56%) who completed the mind-body video routine at least 3 times per week.Conclusion:This intervention improved measures of mental wellness and quality of life with high satisfaction and reasonable adherence. Future studies could explore strategies to optimize adherence and target fatigue.
The Evolution of Employee Assistance Programs to Best Support Healthcare Organizations
Authors: Couser Gregory P. , Nation Jody L. , Apker Dennis P. , Connaughty Susan M. , Hyde Mark A. 
Published: November 2023

Goal:Employee assistance programs (EAPs) have been evolving since they first became prevalent in the 1970s. The important counseling component of EAPs is sometimes lost in discussions about what they do, with many EAPs marketing a broad portfolio of services such as childcare, elder care, legal referral, and other concierge services rather than counseling. The objective of this study was to examine outcomes for the EAP of one organization (Mayo Clinic), compare them to outcomes reported in the literature, and gain insights to help all healthcare organizations best support their employees.Methods:Consistent with customary EAP practice, data for this study was collected through an anonymous survey link distributed by e-mail to users of individual counseling as well as users of organizational consulting services such as advising leaders and supervisors and leading educational sessions.Principal Findings:All (n= 82) individual counseling respondents indicated they would recommend the EAP, none reported worse symptoms, 90% decreased their stress levels, 92% reduced their feelings of anxiety, 88% enjoyed an overall improvement in mood, and 95% developed new skills. If their concern was work-related, 96% agreed the counselor understood the work culture and was able to provide helpful guidance; of the clients who were feeling burned out, 86% agreed they gained strategies to reduce its symptoms. Thematic analysis of individual counseling services indicated that participants highly valued their counselors. Regarding organizational consulting services, respondents (n= 50) indicated EAP services increased their confidence as leaders, supported their work, and provided tangible guidance. They appreciated having an internal EAP counselor. Thematic analysis of organizational consulting services indicated that EAP supported leaders by listening, coaching, and empowering them to normalize issues.Practical Applications:EAPs have evolved into distinct internal, external, and hybrid internal–external models. Internal model counselors are company employees with inside knowledge of company culture, external EAP model counselors are contracted outside of the company, and hybrid models combine a small cadre of internal counselors with the support of outside contractors. Regardless of the model, EAP counselors must collaborate with internal stakeholders, notably the human resources department, to efficiently identify and troubleshoot employee relational issues and allow for customized initiatives to improve mental health. Based upon these findings and the authors' direct experiences with EAP providers, components of an ideal EAP are outlined to show how EAPs can best support employees. Healthcare leaders seeking to add EAP services are advised to focus on offerings that are custom fit to the organization.
Markers of cardiac dysfunction associated with inflammation in a cohort of patients with acute decompensation of cirrhosis
Authors: Voiosu Andrei M. , Daha Ioana C. , Drăgan Victor , Birligea Mihaela , Vîjan Ancuța , Bălănescu Paul , Benguș Andreea , Voiosu Theodor A. , Mateescu Radu B. , Băicuș Cristian R. 
Published: November 2023

Background and aims
Inflammation underpinning acute decompensation (AD) of liver disease is an important driver for the development of acute-on-chronic liver failure or death. We aimed to investigate associations between inflammatory biomarkers and impaired cardiac function in patients admitted for AD of cirrhosis.

Methods
This is a retrospective analysis of a well-characterized prospective cohort of patients with AD of liver disease admitted to a tertiary referral center. All patients had echocardiographic assessment of cardiac function and serum samples at admission. We reclassified patients according to the CLIF-C AD score, measured inflammatory (IL-6, IL-8, TNF-ɑ, CD206) and cardiac-specific (NT-proBNP, troponin T) biomarkers and tested for associations with echocardiographic parameters of cardiac function. We explored the impact on outcome of these factors in multivariate analysis.

Results
We included 70 patients (58 ± 10 years, 28 women), with a mean CLIF-C AD score of 47 ± 7. Thirty-nine patients (56%) fulfilled the echocardiographic criteria for cardiac dysfunction. We found associations between parameters of diastolic dysfunction and serum concentrations of IL-6 and CD206. Echocardiographic parameters of cardiac function were not associated with markers of liver dysfunction such as the CLIF-C AD score. In multivariate analysis higher MELD, higher NT-proBNP, and IL-8 concentrations as well as the absence of echocardiographic criteria for cardiac dysfunction significantly associated with death during follow-up.

Conclusion
We found evidence in favor of a clinically relevant link between serum biomarkers of inflammation (IL-6, CD206) and echocardiographic signals of cardiac dysfunction in patients with acutely decompensated cirrhosis.
Concurrence of inflammatory bowel disease with multiple sclerosis or Hodgkin lymphoma
Authors: Sonnenberg Amnon , Duong Hao T. , McCarty Daniel J. , El-Serag Hashem B. 
Published: November 2023

Background and aims
Epidemiologic evidence suggests that Hodgkin lymphoma (HL) and multiple sclerosis (MS) share a common set of risk factors with Crohn’s disease (CD) and ulcerative colitis (UC). It was hypothesized that such shared risk factors would lead to clustering of the 4 diagnoses in the same patients.

Methods
All patients with HL, MS, CD, or UC were identified in the veterans population from 2016–2020 and the Medicare population from 1986 to 1989. In a case-control study, the observed concurrences amongst these 4 diagnoses were compared with their expected frequencies in the overall veterans or Medicare population during the same time period by calculating odds ratios (OR) with their 95% confidence intervals (CI).

Results
The study included 6 million veterans and 35 million Medicare patients. In the veterans population, inflammatory bowel disease (IBD) was significantly associated with a concurrent diagnosis of HL (OR: 1.40, 95% CI: 1.15–1.71) and MS (1.34, 1.19–1.50). In the Medicare population, IBD was also significantly associated with HL (1.84, 1.07–3.17) and MS (2.31, 1.59–3.35). Similar trends were observed in CD or UC when analyzed separately in both datasets. In the veterans population, adjustment for the potentially confounding influence of ethnicity, sex, and age left all OR values largely unaffected and statistically significant.

Conclusion
The concurrence of IBD with HL or MS could reflect on a common pathway in the etiology or pathogenesis of these 4 diseases.
Efficacy and safety comparison between Lenvatinib and Sorafenib in hepatocellular carcinoma treatment: a systematic review and meta-analysis of real-world study
Authors: Hua Xuefeng , Yin Ziwei , Liang Jin , Chen Wenbin , Gong Hui 
Published: November 2023

Objective
Our study aimed to evaluate the efficacy and safety of Lenvatinib compared with Sorafenib for treating hepatocellular carcinoma (HCC) patients under real-world setting.

Methods
We retrieved relevant literature through the PubMed, Embase, Web of Science, and Cochrane Library databases from 1 January 2000 to 25 June 2022. The differences in overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) as well as treatment adverse related events were evaluated between HCC patients treated with Lenvatinib and Sorafenib using fixed or random-effects models. The MINORS evaluation questionnaire was used to assess the quality of the included literature.

Results
This meta-analysis included a total of 9 single-arm studies and 6 comparative studies. In the meta-analysis, Lenvatinib showed significantly longer median OS than Sorafenib (P < 0.01, MD = 1.20, 95% CI [0.92–1.48]), as well as median PFS (P < 0.01, OR = 2.68, 95% CI [1.59–3.76]), and higher ORR(P < 0.01, OR = 5.36, 95% CI [3.42–8.40]), DCR(P < 0.01, OR = 2.17, 95% CI [1.64–2.86]). The occurrence of Hypertension was higher in Lenvatinib than in Sorafenib treatment (P < 0.01, MD = 5.27, 95% CI [2.38–11.66]), and there was no significant difference in Hand-foot syndrome between Lenvatinib and Sorafenib.

Conclusion
We found that treatment with Lenvatinib in HCC patients resulted in better OS, PFS, and higher ORR and DCR compared to Sorafenib. However, safety data indicated that Lenvatinib did not exhibit a significant advantage.
Health System Perspective on Cost for Delivering a Decision Aid for Prostate Cancer Using Time-driven Activity-based Costing
Authors: Ho David R. , Kaplan Robert , Bergman Jonathan , Penson David F. , Waterman Benjamin , Williams Kristen C. , Villatoro Jefersson , Kwan Lorna , Saigal Christopher S. 
Published: November 2023

Background:
Previsit decision aids (DAs) have promising outcomes in improving decisional quality, however, the cost to deploy a DA is not well defined, presenting a possible barrier to health system adoption.

Objectives:
We aimed to define the cost from a health system perspective of delivery of a DA.

Research Design:
Observational cohort.

Patients and Methods:
We interviewed or observed relevant personnel at 3 institutions with implemented DA distribution programs targeting men with prostate cancer. We then created process maps for DA delivery based on interview data. Cost determination was performed utilizing time-driven activity-based costing. Clinic visit length was measured on a subset of patients. Decisional quality measures were collected after the clinic visit.

Results:
Total process time (minutes) for DA delivery was 10.14 (UCLA), 68 (Olive View-UCLA), and 25 (Vanderbilt). Total average costs (USD) per patient were $38.32 (UCLA), $59.96 (Olive View-UCLA), and $42.38 (Vanderbilt), respectively. Labor costs were the largest contributors to the cost of DA delivery. Variance analyses confirmed the cost efficiency of electronic health record (EHR) integration. We noted a shortening of clinic visit length when the DA was used, with high levels of decision quality.

Conclusions:
Time-driven activity-based costing is an effective approach to determining true inclusive costs of service delivery while also elucidating opportunities for cost containment. The absolute cost of delivering a DA to men with prostate cancer in various settings is much lower than the system costs of the treatments they consider. EHR integration streamlines DA delivery efficiency and results in substantial cost savings.
Costs to Implement a Pediatric Weight Management Program Across 3 Distinct Contexts
Authors: Smith Natalie Riva , Simione Meg , Farrar-Muir Haley , Granadeno Jazmin , Moreland Jennifer W. , Wallace Jessica , Frost Holly M. , Young Jackie , Craddock Cassie , Sease Kerry , Hambidge Simon J. , Taveras Elsie M. , Levy Douglas E. 
Published: November 2023

Background:The Connect for Health program is an evidence-based program that aligns with national recommendations for pediatric weight management and includes clinical decision support, educational handouts, and community resources. As implementation costs are a major driver of program adoption and maintenance decisions, we assessed the costs to implement the Connect for Health program across 3 health systems that primarily serve low-income communities with a high prevalence of childhood obesity.Methods:We used time-driven activity-based costing methods. Each health system (site) developed a process map and a detailed report of all implementation actions taken, aligned with major implementation requirements (eg, electronic health record integration) or strategies (eg, providing clinician training). For each action, sites identified the personnel involved and estimated the time they spent, allowing us to estimate the total costs of implementation and breakdown costs by major implementation activities.Results:Process maps indicated that the program integrated easily into well-child visits. Overall implementation costs ranged from $77,103 (Prisma Health) to $84,954 (Denver Health) to $142,721 (Massachusetts General Hospital). Across implementation activities, setting up the technological aspects of the program was a major driver of costs. Other cost drivers included training, engaging stakeholders, and audit and feedback activities, though there was variability across systems based on organizational context and implementation choices.Conclusions:Our work highlights the major cost drivers of implementing the Connect for Health program. Accounting for context-specific considerations when assessing the costs of implementation is crucial, especially to facilitate accurate projections of implementation costs in future settings.
Abnormal functional connectivity strength in age-related macular degeneration patients: a fMRI study
Authors: Cai Yue-Hong , Huang Xin 
Published: November 2023

ObjectiveAge-related macular degeneration (AMD) is a serious blinding eye disease. Previous neuroimaging studies reported that AMD were accompanied by abnormalities of the brain. However, whether AMD patients were associated with functional connectivity strength (FCS) or not remains unknown. In our study, the purpose of the study was to assess FCS changes in AMD patients.MethodsIn our study, 20 AMD patients and 20 healthy controls (HCs), matched closely by sex, age, and educational level were underwent MRI scanning. FCS method and seed-based functional connectivity (FC) method were applied to investigate the functional network changes between two groups. Moreover, support vector machine (SVM) method was applied to assess the FCS maps as a feature to classification of AMD diseases.ResultsOur study reported that AMD patients showed decreased FCS values in the bilateral calcarine, left supplementary motor area, left superior parietal lobule and left paracentral lobule (ParaL) relative to the HC group. Meanwhile, our study found that the AMD patients showed abnormal FC within visual network, sensorimotor network and default mode network. Moreover, the SVM method showed that FCS maps as machine learning features shows good classification efficiency (area under curve = 0.82) in the study.ConclusionOur study demonstrated that AMD patients showed abnormal FCS with the visual network, sensorimotor network and default mode network, which might reflect the impaired vision, cognition and motor function in AMD patients. In addition, FCS indicator can be used as an effective biological marker to assist the clinical diagnosis of AMD.
The neuronal homeobox transcription factor HMX3 is a crucial vulnerability factor in MECOM-negative KMT2A::MLLT3 acute myelomonocytic leukemia
Authors: Arza-Apalategi Saioa , Heuts Branco M. H. , Bergevoet Saskia M. , Meering Roos , Gilissen Daan , Jansen Pascal W. T. C. , Krippner-Heidenreich Anja , Valk Peter J. M. , Vermeulen Michiel , Heidenreich Olaf , Haferlach Torsten , Jansen Joop H. , Martens Joost H. A. , van der Reijden Bert A. 
Published: November 2023

AbstractThe KMT2A::MLLT3 fusion protein causes acute myeloid leukemia (AML) by activating the oncogenic transcription factor MECOM. However,MECOMexpression occurs in only half of the KMT2A::MLLT3 cases. By integrating gene expression and enhancer activity data from patient cells, we identified neuronal homeobox transcription factorHMX3as cell fate determining factor inMECOM-negative KMT2A::MLLT3 AML.HMX3expression associated with younger age and KMT2A-rearranged leukemia in large AML cohorts (p<0.002).HMX3was not expressed in other major genetic risk groups and healthy blood cells. Transcriptomic analyses revealed thatHMX3drives cancer-associatedE2F,MYCand cell cycle gene programs. EctopicHMX3expression completely inhibited monocytic but not granulocytic colony formation of healthy CD34+adult cells. Silencing ofHMX3in KMT2A::MLLT3 AML cell lines and patient cells resulted in cell cycle arrest, monocytic differentiation, and apoptosis. Thus, HMX3 is a leukemia-specific vulnerability that enhances proliferation and blocks differentiation of MECOM-negative KMT2A::MLLT3 leukemia.
A family of bacterial actin homologues forms a 3-stranded tubular structure
Authors: Bergeron Julien R.C. , Lale-Farjat Shamar L. M. , Lewicka Hanna M. , Parry Chloe , Kollman Justin M. 
Published: November 2023

AbstractThe cytoskeleton plays a critical role in the organization and movement of cells. In Eukaryotes, actin filaments polymerize into a highly conserved double-stranded linear filamentous structure in the presence of ATP, and disassemble upon ATP hydrolysis. Bacteria also possess actin-like proteins, that drive fundamental cellular function, including cell division, shape maintenance, and DNA segregation. Like eukaryotic actin, bacterial actins assemble upon ATP binding. Longitudinal interactions between bacterial actin protomers along each strand are conserved with eukaryotic actin, but variation in interactions between strands gives rise to striking diversity of filament architectures. Here, we report a family of bacterial actins of unknown function, conserved amongst theVerrucomicrobiotaphylum, which assembles into a unique tubular structure in the presence of ATP. A cryo-EM structure of the filaments reveals that it consists of three strands, unlike other described bacterial actin structures. This architecture provides new insights into the organization of actin-like filaments, and has implications for understanding the diversity and evolution of the bacterial cytoskeleton.
Resting State Network alterations during Deep Brain Stimulation in Parkinson’s Disease
Authors: Kandemir Ahmet Levent , Schnitzler Alfons , Florin Esther 
Published: November 2023

AbstractBackgroundCurrent treatment strategies for Parkinson’s disease (PD) include medication and deep brain stimulation (DBS). While these treatment options are effective, their exact mechanisms remain elusive.ObjectivesWe aim at identifying alterations in whole-brain electrophysiological resting state networks (RSNs) due to DBS and medication with the objective to gain insights into neural correlates of DBS and medication.MethodsWe recorded 18 PD patients with DBS at rest in the magnetoencephalogram (MEG) in 4 conditions: medication off - stimulation off, medication off - stimulation on, medication on - stimulation off, and medication on - stimulation on. We derived RSNs and determined 4 consistent networks across conditions: visual, frontal auditory, and SMN (sensorimotor network).ResultIn the SMN, medication had a suppressing effect on functional connectivity. Surprisingly, we could not find a significant change due to DBS. Both medication and stimulation increased functional connectivity in the frontal network. In the auditory network, stimulation decreased functional connectivity while medication both decreased and increased functional connectivity in some parts of the network. Finally, medication and stimulation had opposing effects on the visual network: medication suppressed while DBS increased functional connectivity.ConclusionOverall, our findings reveal that DBS and medication have differential effects on various RSNs, which is relevant for understanding not only their complementary treatment effects but also the side effects.