bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cancer-Related Fatigue Is Associated With Objective Measures of Physical Function Before and After a Clinical Exercise Program: A Retrospective Analysis
Authors: Marker Ryan J. , Wechsler Stephen , Leach Heather J. 
Published: January 2024

Background:
Cancer-related fatigue (CRF) is a common symptom reported by survivors of cancer. CRF is associated with reduced self-reported physical function, but associations with objective measures of physical function are less robust. Exercise programs have been shown to improve both CRF and objective physical function, but the interaction of exercise, CRF, and function has not been explored.

Methods:
Retrospective data were collected from baseline (n = 420) and final assessments (n = 234) of survivors who participated in a 3-month clinical exercise program. Assessments included measures of CRF (Functional Assessment of Chronic Illness Therapy–Fatigue) and physical function (6-minute walk test, usual and fast gait speed, 30-second sit-to-stand test, and the Timed Up and Go test). Multiple regression analyses investigated associations between CRF and physical function before and after the program. CRF and functional changes following the program were calculated and associations investigated with multiple regressions.

Results:
All measures of CRF and physical function significantly improved following the program (P < .01). CRF was associated with all functional measures at baseline (standardized β = −0.18 to 0.29, P < .01) and final assessments (r = −0.27 to 0.26, P < .01). Changes in CRF were associated with changes in function (standardized β = −0.12 to 0.23, P < .05), except usual gait speed (P = .17).

Conclusion:
This investigation demonstrated associations between CRF and objective physical function before and after participation in an exercise program. The 3-way interaction between CRF, physical function, and exercise can be used clinically to personalize rehabilitation strategies. Future studies should investigate changes in CRF and function during an exercise program.
Evidence of “Repeated Admission Bias” Among Those Who Use Injection Drugs Across 2 Decades of US Treatment Admissions: 2000–2020
Authors: Bormann Nicholas L. , Arndt Stephan 
Published: January 2024

Objectives
Encounter-based datasets like the Treatment Episode Dataset—Admissions (TEDS-A) are used for substance use–related research. Although TEDS-A reports the number of previous treatment admissions, a limitation is this reflects encounters, not people. We sought to quantify the methodologic bias incorporated by using all encounters versus initial encounters and assess if this risk is evenly distributed across all routes of drug administration.

Methods
TEDS-A 2000–2020 dataset with nonmissing primary substance data was used. Of the data, 3.17% were missing the usual administration route, and 11.9% were missing prior admission data. Prior admissions are documented as 0 through 4, then binned for 5 or greater (5+). Risk of admission bias was defined as odds ratio (ORRAB): odds of total admissions relative to the odds of the first admission. Bootstrap confidence intervals were generated (5000 iterations) across administration routes and demographics; however, their widths were <0.0055 and not reported.

Results
There were 38,238,586 admissions over the 21 years, with 13,865,517 (41.2%) first admissions. Of all admissions, 15.7% indicated injection drug use (IDU); 26.3% of encounters reporting IDU were in the 5+ group. This resulted in an ORRAB of 1.77. White enrollees had an elevated ORRAB (1.05), whereas among Latinos, ORRAB was low (0.74).

Conclusions
Using encounter-based datasets can introduce bias when including all admissions versus exclusively initial treatment episodes. This report is the first to quantify this bias and shows that individuals with IDU are at highest risk for returning to treatment, thereby over-representing this method of use when all encounters are used.
An Inpatient Protocol for the Treatment of Methamphetamine Withdrawal in Patients With and Without Opioid Use Disorder
Authors: Wilens Timothy E. , Wilson Ronan L. H. , Beltrame Lia , Taylor Adam , O’Connell James 
Published: January 2024

Objective
Increasing rates of methamphetamine (METH) use, use disorders, and related overdoses are a growing public health problem. There are a lack of protocols addressing METH intoxication and withdrawal symptoms that manifest during acute withdrawal treatment resulting in inpatient management difficulties and premature discharges. This report presents a novel treatment protocol comprised of behavior-targeted and pharmacological components that aims to reduce the intensity and duration of METH intoxication and withdrawal related symptoms during early treatment, improve retention, and provide clinicians with a tool to meet this growing problem.

Methods
The protocol was developed by a team of addiction physicians and other clinical staff. Clinical and administrative staff at a community acute stabilization unit were trained and the protocol was implemented with patients presenting with METH use. Pharmacological interventions, including ascorbic acid, antipsychotics, and other sedatives are discussed, as are behavior-based orders. A retrospective quality assurance examination was conducted on patient characteristics and outcomes as well as focus groups with nursing staff.

Results
A total of 23 patients consecutively admitted to the unit used the protocol (100% male). Most patients (67%) displayed symptoms of METH use or withdrawal. Behavior-related interventions were used in 52% of patients, while 48% received behavior-related and pharmacological measures. Patient completion of the protocol was 83%, and the protocol’s utility was supported by nursing staff.

Conclusions
This retrospective evaluation of a novel METH withdrawal treatment protocol suggests feasibility, tolerability, and preliminary evidence of effectiveness, providing clinicians with a new tool that requires further study.
The effect of emotion regulation on the emotional modulation of pain and nociceptive flexion reflex
Authors: Toledo Tyler A. , Vore Claudia N. , Huber Felicitas A. , Rhudy Jamie L. 
Published: January 2024

Abstract
Positive emotions inhibit pain, whereas negative emotions facilitate pain. Thus, many psychosocial interventions capitalize on this emotion–pain relationship to improve patients' abilities to regulate emotion (ie, reduce negative emotion, increase positive emotion), influence nociception, and manage pain. This study extended the existing literature to examine whether emotion regulation procedures could influence emotional modulation of the nociceptive flexion reflex (NFR), a marker of spinal nociception. To elicit emotion, 2 blocks of pleasant, neutral, and unpleasant pictures were presented. In block 1, participants were asked to passively view pictures during which painful electric stimulations were delivered to evoke pain and the NFR. Valence, arousal, corrugator electromyogram, and skin conductance response were used to measure emotional responses to pictures. To manipulate emotion regulation, participants were randomized to either suppress (downregulate) or enhance (upregulate) their emotion during block 2 (other procedures same as block 1). Instructions to suppress decreased subjective and physiological responding to emotional pictures, reduced emotional modulation of pain, and generally decreased NFR magnitude (regardless of picture content). Instructions to enhance emotion increased subjective responding to emotional pictures but did not alter physiological responding to pictures or emotional modulation of pain/NFR in predictable ways. Results imply that downregulation/suppression of negative emotions may work best to reduce pain facilitation. Furthermore, this study contributes to the existing literature that shows that pain and pain signaling is tightly coupled with emotional states and that emotion regulation can impact pain perception.
Liraglutide in Obese or Overweight Individuals With Stable Bipolar Disorder
Authors: McElroy Susan L. , Guerdjikova Anna I. , Blom Thomas J. , Mori Nicole , Romo-Nava Francisco 
Published: January 2024

Abstract

Background
Obesity is common among persons with bipolar disorder (BD). Liraglutide 3.0 mg/d subcutaneous injection is indicated for chronic weight management and associated with minimal adverse neuropsychiatric effects. This study evaluated whether liraglutide 3 mg/d reduced body weight, improved metabolic factors and eating psychopathology, and was safe and well tolerated in persons with stable BD who were obese (body mass index [BMI] >30 kg/m2) or overweight (BMI ≥27 kg/m2) with at least one weight-related comorbidity.

Methods
This was a 40-week, randomized (1:1 ratio), placebo-controlled, double-blind, parallel-group, 2-arm clinical trial of liraglutide targeted to 3.0 mg/d (in combination with a reduced-calorie diet and increased physical activity) in 60 participants with stable BD who were obese or overweight. Primary outcome was percent change in body weight from baseline to study end. Secondary outcomes included percentage of patients who lost ≥5% of baseline body weight, and changes in metabolic variables and measures of eating psychopathology.

Results
There were no significant baseline differences between the 29 liraglutide recipients and the 31 placebo recipients, except that liraglutide recipients had higher levels of binge eating and lower levels of high-density lipoprotein cholesterol. Compared with placebo, liraglutide was associated with significantly greater reductions in percent change in body weight, percentage of participants who lost at least 5% of body weight, and reductions in weight, BMI, hemoglobin A1c levels, binge eating, and hunger. Liraglutide was well tolerated.

Conclusions
Liraglutide 3 mg/d may be efficacious and safe for weight loss in individuals with stable BD and obesity or overweight.

Registration details

ClinicalTrials.gov (NCT03158805).
Dextromethorphan/Bupropion: A Novel Treatment for Patients With Major Depressive Disorder
Authors: Willett Kristine C. , Bond LeDea R. , Morrill Amanda M. , Dima Lorena , Ifteni Petru 
Published: January 2024

Background:
Major depressive disorder (MDD) affects millions of people and is the leading cause of disability worldwide. Patients report decreased quality of life and ability to perform activities of daily living. It is estimated that the current standard of care, which includes pharmacologic therapy with a selective serotonin reuptake inhibitor, is effective in 40%–60%. Additional treatment options are warranted. The combination of dextromethorphan (DEX) and bupropion (BUP) (Auveulty) was approved for treatment in 2022. This unique combination offers an interesting mechanism of action and favorable onset of action for patients with MDD.

Pharmacodynamics and Pharmacokinetics:
The mechanism of action of DEX–BUP when used in combination is unique. DEX is a noncompetitive N-methyl-d-aspartate receptor antagonist rapidly metabolized through the CYP450 2D6. BUP is an aminoketone and CYP2D6 inhibitor, which results in increased plasma levels of DEX through competitive CYP2D6 inhibition.

Clinical Trials:
In a phase 2 clinical study, the efficacy of DEX-BUP was compared with BUP alone in patients with clinically diagnosed MDD. At baseline, participants had moderate-to-severe depression using the Montgomery–Asberg Depression Rating Scale (MADRS) and Clinical Global Impressions Severity (CGI-S) scales. There was a significant overall reduction in MADRS and CGI-S scores in the treatment group compared with the BUP monotherapy with improvement observed as early as week 1 of treatment. Later, a phase 3 study was conducted comparing DEX-BUP 45 mg/105 mg with placebo in patients with moderate-to-severe MDD. Similarly, MADRS and CGI-S scores were significantly reduced in the treatment group. Adverse effects were similar in all groups.

Therapeutic Advance:
Clinical response to first line treatment options for MDD are reported to be 40%–60%. Availability of additional treatment options, particularly those with reduced time to efficacy, may improve overall treatment and patient quality of life. DEX–BUP is a combination option that has been shown to improve depression symptoms as early as 1 week after initiation.
Computer Simulation to Assess Emergency Department Length of Stay in Pediatric Traumatic Brain Injury
Authors: Feng Tianshu , Ajdari Ali , Boyle Linda Ng , Kannan Nithya , Burd Randall , Groner Jonathan I. , Farneth R. Austin , Vavilala Monica S. 
Published: January 2024

Abstract

Objectives
Our study aimed to identify how emergency department (ED) arrival rate, process of care, and physical layout can impact ED length of stay (LOS) in pediatric traumatic brain injury care.

Methods
Process flows and value stream maps were developed for 3 level I pediatric trauma centers. Computer simulation models were also used to examine “what if” scenarios based on ED arrival rates.

Results
Differences were observed in prearrival preparation time, ED physical layouts, and time spent on processes. Shorter prearrival preparation time, trauma bed location far from diagnostic or treatment areas, and ED arrival rates that exceed 20 patients/day prolonged ED LOS. This was particularly apparent in 1 center where computer simulation showed that relocation of trauma beds can reduce ED LOS regardless of the number of patients that arrive per day.

Conclusions
Exceeding certain threshold ED arrival rates of children with traumatic brain injury can substantially increase pediatric trauma center ED LOS but modifications to ED processes and bed location may mitigate this increase.
Long-term Effects of Kidney Transplantation Compared With Dialysis on Intima–media Thickness in Children—Results From the 4C-T Study
Authors: Grabitz Carl , Sugianto Rizky I. , Doyon Anke , Azukaitis Karolis , Anarat Ali , Bacchetta Justine , Bayazit Aysun K. , Bulut Ipek K. , Caliskan Salim , Canpolat Nur , Duzova Ali , Harambat Jerome , Kiyak Aysel , Longo Germana , Obrycki Lukasz , Paripovic Dusan , Thurn-Valsassina Daniela , Yilmaz Alev , Shroff Rukshana , Schaefer Franz , Schmidt Bernhard M.W. , Melk Anette ,   for the 4C Study Consortium
Published: January 2024

Background.
Children requiring kidney replacement therapy experience high burden of cardiovascular (CV) disease leading to increased mortality. Intima–media thickness (IMT) indicating atherosclerosis is a validated surrogate marker for future CV events.

Methods.
We investigated the effect of different treatment modalities (dialysis, preemptive kidney transplantation (KTx), late KTx after dialysis) on IMT by multivariable linear mixed-effect modeling. Patients were enrolled in a prospective cohort study.

Results.
A total of 261 analyzed children had a mean follow-up of 3 y. Children after preemptive and late KTx had lower levels of IMT when compared with dialysis. Using an interaction term, a significant progression of IMT over time was seen during dialysis (β = 0.0053 mm/y, P  =  0.004). IMT before the start of therapy was the most influential determinant in all models. Low IMT was associated with maintenance steroid treatment after preemptive KTx. High IMT on dialysis was associated with higher systolic blood pressure, lower body mass index, lower serum albumin, and lower bicarbonate.

Conclusions.
IMT remained rather stable in children several years after KTx. In contrast, children on dialysis had higher IMT values, which increased over time. In these children, blood pressure control, calorie and protein intake, and acid–base homeostasis seem important. Taken together, children might profit from early transplantation to limit accumulation of CV risk.
Non-Degenerate Two-Photon Imaging of Deep Rodent Cortex using Indocyanine Green in the water absorption window
Authors: Tomar Alankrit , Engelmann Shaun A. , Woods Aaron L. , Dunn Andrew K. 
Published: January 2024

AbstractWe present a novel approach for deep vascular imaging in rodent cortex at excitation wavelengths susceptible to water absorption using two-photon microscopy with photons of dissimilar wavelengths. We demonstrate that non-degenerate two-photon excitation (ND-2PE) enables imaging in the water absorption window from 1400-1550 nm using two synchronized excitation sources at 1300 nm and 1600 nm that straddle the absorption window. We explore the brightness spectra of indocyanine green (ICG) and assess its suitability for imaging in the water absorption window. Further, we demonstratein vivoimaging of the rodent cortex vascular structure up to 1.2 mm using ND-2PE. Lastly, a comparative analysis of ND-2PE at 1435 nm and single-wavelength, two-photon imaging at 1300 nm and 1435 nm is presented. Our work extends the excitation range for fluorescent dyes to include water absorption regimes and underscores the feasibility of deep two-photon imaging at these wavelengths.
Heterogeneity in deaths of despair: excess mortality in the US during the Covid-19 pandemic
Authors: Kandula Sasikiran , Keyes Katherine M. , Shaman Jeffrey 
Published: January 2024

AbstractThe impact of Covid-19 on mortality includes both direct effects of the virus and indirect effects mediated through other causal pathways. In the United States, the indirect effects, particularly from suicides, overdoses and alcohol-induced causes (i.e. deaths of despair) (1) are understudied. Here, we estimated excess non-Covid deaths and deaths of despair, in the US overall, in each state and in 72 demographic strata. Nationally, 114,230 (127,597) excess non-Covid deaths, 19,074 (33,559) excess poisoning deaths and 8,746 (13,771) excess alcohol-induced deaths were estimated during 2020 (2021). Excess poisoning and alcohol-induced mortality were highest among the 35-44 and the 55-64 year groups, respectively. The Black and the American Indian/Alaskan Native populations had the highest excess poisoning and alcohol-induced mortality, respectively. Fewer suicides than expected occurred nationally, but excess suicides were estimated among Black youth. These findings suggest that additional resources need to be mobilized to limit increases in deaths of despair.
The multiverse of data preprocessing and analysis in graph-based fMRI: A systematic literature review of analytical choices fed into a decision support tool for informed analysis
Authors: Kristanto Daniel , Burkhardt Micha , Thiel Christiane , Debener Stefan , Gießing Carsten , Hildebrandt Andrea 
Published: January 2024

AbstractThe large number of different analytical choices researchers use may be partly responsible for the replication challenge in neuroimaging studies. For robustness analysis, knowledge of the full space of options is essential. We conducted a systematic literature review to identify the analytical decisions in functional neuroimaging data preprocessing and analysis in the emerging field of cognitive network neuroscience. We found 61 different steps, with 17 of them having debatable options. Scrubbing, global signal regression, and spatial smoothing are among the controversial steps. There is no standardized order in which different steps are applied, and the options within several steps vary widely across studies. By aggregating the pipelines across studies, we propose three taxonomic levels to categorize analytical choices: 1) inclusion or exclusion of specific steps, 2) distinct sequencing of steps, and 3) parameter tuning within steps. To facilitate access to the data, we developed a decision support app with high educational value called METEOR, which allows researchers to explore the space of choices as reference for well-informed robustness (multiverse) analysis.HighlightsData analysis variability in neuroimaging hinders replicability.Analysis across multiple defensible options examines the robustness of results.We conducted a systematic literature review to identify analytical options.We identified 61 steps and 102 options in performing graph-fMRI analysis.Interactive visualization of these steps and options is available as a Shiny app.
A functional medicine and food homology composition discovery based on disease-related target and data mining against cardiac remodeling
Authors: Xiao Dan , Li Runze , Qin Xiaoqing , Feng Jinhai , Baranenko Denis , Natdochii Liudmila , Zhou Yingyu , Liu Jicheng , Lin Yan 
Published: January 2024

AbstractBackgroundMedicine and food homological (MFH) products exhibit enhanced safety and tolerability, minimizing notable side effects, making them pivotal for prolonged use in cardiovascular diseases. This study aims to identify functional compounds in MFH based on cardiac remodeling-related target, employing reliable, comprehensive, and high-throughput methods.MethodsBy bioinformatics andin vivoverifications, we initially investigated the key target in the progression of cardiac remodeling. Subsequently, we performed molecular docking among medical homology compound database (MHCD), and then performed drug-likeness evaluations to recognize functional component based on disease-related target. Pharmacological verifications and data mining including cardiac and medullary transcriptomics, neurotransmitter metabolomics, resting-state functional magnetic resonance imaging (rs-fMRI), and correlationship analysis were utilized to define the benefical effects of MFH functional components, as well as its in-depth mechanims.ResultsThe critical roles of oxidative stress and the key target of NRF2 in cardiac remodeling were discovered, and β-ecdysterone was screened as the most promising NRF2 enhancer in MHCD. Dose-dependent efficacy of β-ecdysterone in countering oxidative stress and ameliorating cardiac remodeling were then verfied byin vivoandex vivoexperiments. By data mining, the crosstalk mechanism between cardiac remodeling and neuromodulation was identified, and further unveiledSlc41a3as a potential key factor influenced by β-ecdysterone. Additionally, β-ecdysterone mitigated increases in norepinephrine (NE) and its metabolites DHPG in the sympathetic nerve center hypothalamic paraventricular (PVN), as indicated by rs-fMRI. Cardiac and medullary transcriptomes revealed central-peripheral regulation signaling pathways during cardiac remodeling with the involvement of core gene ofDhx37.ConclusionsOur study identified β-ecdysterone as a natural MFH functional compound countering cardiac remodeling by targeting NRF2 elevation. It elucidates crosstalk between cardiac remodeling and neuromodulation, facilitating precise drug screening and mechanistic insights, providing substantial evidence for β-ecdysterone application and molecular mechanisms in cardiovascular diseases.
A gene regulatory network for specification and morphogenesis of a Mauthner Cell homolog in non-vertebrate chordates
Authors: Kim Kwantae , Piekarz Katarzyna M. , Stolfi Alberto 
Published: January 2024

AbstractTranscriptional regulation of gene expression is an indispensable process in multicellular development, yet we still do not fully understand how the complex networks of transcription factors operating in neuronal precursors coordinately control the expression of effector genes that shape morphogenesis and terminal differentiation. Here we break down in greater detail a provisional regulatory circuit downstream of the transcription factor Pax3/7 operating in the descending decussating neurons (ddNs) of the tunicateCiona robusta.The ddNs are a pair of hindbrain neurons proposed to be homologous to the Mauthner cells of anamniotes, and Pax3/7 is sufficient and necessary for their specification. We show that different transcription factors downstream of Pax3/7, namely Pou4, Lhx1/5, and Dmbx, regulate distinct “branches” of this ddN network that appear to be dedicated to different developmental tasks. Some of these network branches are shared with other neurons throughout the larva, reinforcing the idea that modularity is likely a key feature of such networks. We discuss these ideas and their evolutionary implications here, including the observation that homologs of all four transcription factors (Pax3/7, Lhx5, Pou4f3, and Dmbx1) are key for the specification of cranial neural crest in vertebrates.