bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor Response-speed Heterogeneity as a Novel Prognostic Factor in Patients With Metastatic Colorectal Cancer
Authors: Liu Junjia , Wang Xuefeng , Sahin Ibrahim H. , Imanirad Iman , Felder Seth I. , Kim Richard D. , Xie Hao 
Published: January 2023

Purpose:
Differential tumor response to therapy is partially attributed to tumor heterogeneity. Additional efforts are needed to identify tumor heterogeneity parameters in response to therapy that is easily applicable in clinical practice. We aimed to describe tumor response-speed heterogeneity and evaluate its prognostic value in patients with metastatic colorectal cancer.

Patients and Methods:
Individual patient data from Amgen (NCT00364013) and Sanofi (NCT00305188; NCT00272051) trials were retrieved from Project Data Sphere. Patients in the Amgen 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX) arm were used to establish response-speed heterogeneity. Its prognostic value was subsequently validated in the Sanofi FOLFOX arms and the Amgen panitumumab+FOLFOX arm. Kaplan-Meier method and Cox proportional hazards models were used for survival analyses.

Results:
Patients with high response-speed heterogeneity in the Amgen FOLFOX cohort had significantly shorter (P<0.001) median progression-free survival (PFS) of 7.27 months (95% CI, 6.12-7.96 mo) and overall survival (OS) of 16.0 months (95% CI, 13.8-18.2 mo) than patients with low response-speed heterogeneity with median PFS of 9.41 months (95% CI, 8.75-10.89 mo) and OS of 22.4 months (95% CI, 20.1-26.7 mo), respectively. Tumor response-speed heterogeneity was a poor prognostic factor of shorter PFS (hazard ratio, 4.17; 95% CI, 2.49-6.99; P<0.001) and shorter OS (hazard ratio, 2.57; 95% CI, 1.64-4.01; P<0.001), after adjustment for other common prognostic factors. Comparable findings were found in the external validation cohorts.

Conclusion:
Tumor response-speed heterogeneity to first-line chemotherapy was a novel prognostic factor associated with early disease progression and shorter survival in patients with metastatic colorectal cancer.
Renal Safety of Sacubitril/Valsartan: A Meta-Analysis of Randomized Controlled Trials
Authors: Zheng Shaohua , Zhang Yujiao , Gu Lei , Ma Kai , Wang Xuehan , Hou Yinglong , Zhang Fenglei , Gao Mei 
Published: January 2023

Abstract:
As a first-line therapy, sacubitril/valsartan (S/V) plays a significant role in the treatment of heart failure. However, its effect on renal function is still uncertain. We searched PubMed, EMBASE, the Cochrane Library, and Clinical Trials for randomized controlled trials to evaluate the effect of S/V on renal function in patients. The results are reported as the mean difference, relative ratio, and 95% confidence intervals. A total of 13 randomized controlled trials were included (19,367 patients). Among them, 11 studies focused on patients with heart failure, 1 on patients with acute myocardial infarction, and 1 on patients with chronic kidney disease. We found that fewer worsening renal function events, elevated creatine level events, and severe hyperkalemia events (blood potassium >6.0 mmol/L) occurred in the S/V group than those in the renin–angiotensin–aldosterone system inhibitor (RASi) group. The estimated glomerular filtration rate decreased in both the S/V group and the RASi group, but the change was more obvious in the RASi group. There was no significant difference in hyperkalemia events (blood potassium >5.5 mmol/L) between the 2 groups. Subgroup analysis showed that with the extension of follow-up time (>6 months), worsening renal function events occurred less frequently in the S/V group than in the RASi group. Existing evidence has shown that S/V is superior to RASi in general renal safety. Perhaps with the prolongation of treatment time, the advantages of S/V are more obvious.
Mechanisms of SGLT2 Inhibitors in Heart Failure and Their Clinical Value
Authors: Xie Yafei , Wei Yujie , Li Dan , Pu Jie , Ding Hong , Zhang Xiaowei 
Published: January 2023

Abstract:
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are widely used to treat diabetes mellitus. Abundant evidence has shown that SGLT2 inhibitors can reduce hospitalization for heart failure (HF) in patients with or without diabetes. An increasing number of studies are being conducted on the mechanisms of action of SGLT2 inhibitors in HF. Our review summarizes a series of clinical trials on the cardioprotective effects of SGLT2 inhibitors in the treatment of HF. We have summarized several classical SGLT2 inhibitors in cardioprotection research, including empagliflozin, dapagliflozin, canagliflozin, ertugliflozin, and sotagliflozin. In addition, we provided a brief overview of the safety and benefits of SGLT2 inhibitors. Finally, we focused on the mechanisms of SGLT2 inhibitors in the treatment of HF, including ion-exchange regulation, volume regulation, ventricular remodeling, and cardiac energy metabolism. Exploring the mechanisms of SGLT2 inhibitors has provided insight into repurposing these diabetic drugs for the treatment of HF.
Effect of Dexmedetomidine on Cardiac Surgery Patients
Authors: Xiao Man , Jiang Chong-Fa , Gao Qin , Pan Jue , Zhang Hong , Wu Sheng-Nan , Dou Mao-Sen 
Published: January 2023

Abstract:
Dexmedetomidine, an alpha-2 adrenoreceptor agonist that is widely used as a sedative medication, is becoming more and more attractive in clinical application on cardiac surgery patients. In this review, we aim to summarize and discuss both retrospective studies and clinical trials regarding the effect of dexmedetomidine on patients who underwent cardiac surgery (including coronary artery bypass grafting, valve surgery, aortic surgery, percutaneous coronary intervention, and so on), which illustrates that the clinical effects of dexmedetomidine could effectively reduce mortality, major complications, and the intensive care unit and hospital length of stay without comprising safety. In addition, inconsistent results from both retrospective studies and clinical trials have also been demonstrated. Although the effectiveness and safety of dexmedetomidine on cardiac surgery patients is suggested, high-quality clinical trials are needed for further verification.
Prescription Rates and Prognostic Implications of Optimally Targeted Guideline-Directed Medical Treatment in Heart Failure and Atrial Fibrillation: Insights From The MISOAC-AF Trial
Authors: Moysidis Dimitrios V. , Kartas Anastasios , Samaras Athanasios , Papazoglou Andreas S. , Patsiou Vasiliki , Bekiaridou Alexandra , Baroutidou Amalia , Tsagkaris Christos , Karagiannidis Efstratios , Daios Stylianos , Anastasiou Vasileios , Tsalikakis Dimitrios , Efthimiadis Georgios , Ziakas Antonios , Tzikas Apostolos , Giannakoulas George 
Published: January 2023

Abstract:
Heart failure (HF) and atrial fibrillation (AF) commonly coexist in real-life clinical practice. Among patients with HF with reduced ejection fraction (HFrEF) or HF with mildly reduced ejection fraction (HFmrEF), guidelines call for evidence-based target doses of renin–angiotensin–aldosterone system inhibitors and beta-blockers. However, target doses of guideline-directed medical treatment (GDMT) are often underused in real-world conditions, including HF–AF comorbidity. This retrospective cohort study of a randomized trial (Motivational Interviewing to Support Oral AntiCoagulation adherence in patients with nonvalvular AF) included hospitalized patients with AF and HFrEF or HFmrEF. Optimally targeted GDMT was defined as intake of evidence-based target doses of renin–angiotensin–aldosterone system and beta-blockers at 3 months after discharge. Rates of optimally targeted GDMT achievement across the baseline estimated glomerular filtration rate (eGFR) were assessed. Independent predictors of nontargeted GDMT and its association with all-cause mortality and the composite of cardiovascular death or HF hospitalization were assessed by regression analyses. In total, 374 patients with AF and HFrEF or HFmrEF were studied. At 3 months after discharge, 30.7% received target doses of GDMT medications. The rate of optimally targeted GDMT was reduced by 11% for every 10 mg/min/1.73 m2 decrease in baseline eGFR [adjusted β = 0.99; 95% confidence interval (CI), 0.98–0.99] levels. After a median 31-month follow-up period, 37.8% patients in the optimally targeted GDMT group died, as compared with 67.8% (adjusted hazard ratio: 1.49; 95% CI, 1.05–2.13) in the nontargeted GDMT group. The risk of cardiovascular death or HF hospitalization was also higher in these patients (adjusted hazard ratio: 1.60; 95% CI, 1.17–2.20). Target doses of all HF drugs were reached in roughly one-third of patients with AF and HFrEF or HFmrEF 3 months after hospital discharge. Nontargeted GDMT was more frequent across lower eGFR levels and was associated with worse outcomes.
A qualitative study of the dark and bright sides of physicians' electronic health record work outside work hours
Authors: Attipoe Selasi , Walker Daniel M. , Schweikhart Sharon B. , Hefner Jennifer L. 
Published: January 2023

Background
The introduction of electronic health records (EHRs) has contributed considerably to EHR work outside work (WOW) hours for physicians. Prior research has identified the pressures associated with stress resulting from EHR WOW, yet developing a nuanced understanding of how physicians appraise and respond to this stress, and the resulting impacts, remains absent from the literature.

Purpose
Grounded in the technostress model, this study takes a qualitative approach to explore both the pressures and opportunities associated with EHR WOW.

Methods
Thematic analysis of data from semistructured interviews was utilized to examine the pressures and opportunities associated with EHR WOW among primary care pediatricians (n = 15) affiliated with a large Midwestern pediatric health system.

Results
The physicians in this study regularly spent time working in the EHR outside work hours. They felt the EHR contributed to their documentation burden, which ultimately increased their EHR WOW, and reported a sense of burden from ubiquitous EHR availability. Conversely, they appreciated the flexibility the EHR provided in terms of work–life balance. Suggestions for improvement under the direct purview of practice management included enhanced EHR usability, improvements in workflow during work hours to free up time to document, and more training on both EHR documentation strategies and ongoing software upgrades.

Conclusion
Physicians perceive that the EHR exerts certain pressures while affording new opportunities and conveniences. This study provides evidence of both the pressures and opportunities of EHR WOW and their effect on physician well-being.

Practice Implications
Specific opportunities are identified for health administrators to enable physicians to better manage EHR WOW.
Clinical and Ethical Dilemmas in the Involuntary Treatment of Anorexia Nervosa
Authors: Tumba Jenny , Smith Megan , Rodenbach Kyle E. 
Published: January 2023

Learning objectives
After completing this activity, practitioners will be better able to:
• Discuss the growing body literature emphasizing moderation and harm-reduction in patients with severe and enduring anorexia nervosa (SE-AN)
• Outline and discuss the legal, ethical, and medical challenges inpatient providers face when treating patients with SE-AN

Abstract
Patients with severe and enduring anorexia nervosa (SE-AN) present numerous clinical and ethical challenges for the hospital psychiatrist. Patients typically come to the hospital in a state of severe medical compromise. Common difficulties in the period of acute medical stabilization include assessment of decision-making capacity and the right to decline treatment, as well as legally complex decisions pertaining to administering artificial nutrition over the patient’s objection. Following acute medical stabilization, the psychiatric consultant must decide whether psychiatric hospitalization for continued treatment is indicated, and if so, whether involuntary hospitalization is indicated. The standard of care in these situations is unclear. Pragmatic issues such as lack of appropriate facilities for specialized treatment are common. If involuntary hospitalization is not approved or not pursued, there may be difficulty in determining whether, when, and how to involve palliative care consultants to guide further management. These cases are complex and largely reside in a medico-legal and ethical gray area. This article discusses the difficulties associated with these cases and supports a growing body of literature emphasizing moderation and harm-reduction in patients with SE-AN. Physician-assisted dying (PAD) is also discussed.
Enhanced sodium channel inactivation by temperature and FHF2 deficiency blocks heat nociception
Authors: Marra Christopher , Hartke Timothy V. , Ringkamp Matthias , Goldfarb Mitchell 
Published: January 2023

Abstract
Transient voltage-gated sodium currents are essential for the initiation and conduction of action potentials in neurons and cardiomyocytes. The amplitude and duration of sodium currents are tuned by intracellular fibroblast growth factor homologous factors (FHFs/iFGFs) that associate with the cytoplasmic tails of voltage-gated sodium channels (Navs), and genetic ablation of Fhf genes disturbs neurological and cardiac functions. Among reported phenotypes, Fhf2

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mice undergo lethal hyperthermia-induced cardiac conduction block attributable to the combined effects of FHF2 deficiency and elevated temperature on the cardiac sodium channel (Nav1.5) inactivation rate. Fhf2

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mice also display a lack of heat nociception, while retaining other somatosensory capabilities. Here, we use electrophysiological and computational methods to show that the heat nociception deficit can be explained by the combined effects of elevated temperature and FHF2 deficiency on the fast inactivation gating of Nav1.7 and tetrodotoxin-resistant sodium channels expressed in dorsal root ganglion C fibers. Hence, neurological and cardiac heat-associated deficits in Fhf2

null
mice derive from shared impacts of FHF deficiency and temperature towards Nav inactivation gating kinetics in distinct tissues.
Brachial-femoral pulse wave velocity in 2–4-year-old children: a feasibility study
Authors: Jones Melissa A. , Whitaker Kara M. , Paley Joshua L. , Thrower Alexis , Stoner Lee , Barone Gibbs Bethany 
Published: January 2023

Background
Cardiovascular disease (CVD) progression occurs across the lifespan. However, available measures of CVD risk in young children are limited. Carotid-femoral pulse wave velocity (cfPWV) is a gold-standard, noninvasive measure of CVD risk that has been studied in children ages 6–18 years. Yet, cfPWV has been measured to a lesser extent in younger children, a population whose temperament or attention span may pose unique challenges. Brachial-femoral PWV (bfPWV) may be feasible, more acceptable, and could provide similar CVD risk assessment to cfPWV in younger children. This study aimed to determine the feasibility of bfPWV measurement in children ages 2–4 years including assessment of comparability of bfPWV to cfPWV normative data.

Methods
In 10 children (mean 2.9 ± 0.5 years), oscillometric cuffs were placed on the upper thigh and upper arm. Following a 5-min rest, cuffs were inflated to a subdiastolic pressure three times, and waveforms were captured. Procedures were repeated after a 15-min rest. Measured values were compared to age-predicted cfPWV extrapolated from published normative data in children 6–18 years of age.

Results
We successfully obtained at least one acceptable quality bfPWV scan in all participants. Among the subset with a repeated measurement (n = 5), mean (SD) difference between measurements was 0.013 (0.28) m/s. Mean bfPWV was slightly higher than age-predicted cfPWV (observed: 4.55 m/s; predicted: 3.99 m/s; P = 0.012) with larger residuals among younger children and those not reclined in a chair during measurement.

Conclusion
bfPWV appears to be feasible tool for noninvasive CVD risk assessment in children ages 2–4 years.
Device-guided slow breathing with direct biofeedback of pulse wave velocity – acute effects on pulse arrival time and self-measured blood pressure
Authors: Mengden Thomas , Bachler Martin , Sehnert Walter , Marschall Philip , Wassertheurer Siegfried 
Published: January 2023

Background
There isevidence that device-guided slow breathing using biofeedback acutely reduces blood pressure (BP) and pulse wave velocity [i.e. increased pulse arrival time (PAT)].

Objectives
The objectives of the study presented here were to test whether the results of changes observed in PAT in earlier studies are reproducible over 1 week and how changes in pulse wave velocity/PAT translate into absolute self-measured BP changes.

Methods
Patients with a systolic BP 130–160 mmHg or treated essential hypertension (21 females/23 males) were trained to perform unattended device-guided slow breathing exercises for 10 min daily over 5 days. Furthermore, they were skilled to perform self-measurement of BP before and after the breathing exercise using a validated upper-arm device.

Results
Office BP at screening [median (1, 3. Q)] was 137 (132, 142)/83 (79, 87) mmHg. We observed a significant (P < 0.05) increase in PAT of 5 ms (SD 12.5 ms) on average after 10 min of guided breathing and an additional 1 ms (P < 0.05, SD 8 ms) during the following 5 min of spontaneous breathing compared to baseline. PAT before the exercise remained constant over 5 days paralleled by constant self-measured BP before the exercise. Device-guided breathing was associated with a significant reduction of self-measured SBP of 5 mmHg (P < 0.01, SD 8 mmHg). Data furthermore demonstrated that these changes were highly reproducible over 1 week.

Conclusions
Device-guided slow breathing and biofeedback lead to reproducible and favorable changes (increase) in PAT and SBP (decrease).
Disseminated nontuberculous mycobacteria infection in an immunocompetent host: A case report
Authors: Shin Hye Soon , Yang Bumhee , Kim So Rae , Kim Hee-Sung , Shin Kyeong Seob , Shin Yoon Mi 
Published: January 2023

Rationale:
Disseminated nontuberculous mycobacterial (NTM) infections are rare and occur primarily in immunocompromised hosts. Mycobacterium abscessus complex (MABC), including M abscessus subsp. massiliense (hereafter M massiliense) is a complex of rapidly growing mycobacterial (RGM) species of NTM. Here, we present a rare case of disseminated NTM infection with RGM bacteremia caused by M massiliense in an immunocompetent host.

Patient concerns:
A 64-year-old woman with a recent history of spine fracture and septic pneumonia was transferred to our emergency room for dyspnea and fever. A peripherally inserted central catheter (PICC) had been placed over 6 months prior.

Diagnoses:
Chest computed tomography (CT) showed multifocal patchy consolidations and ground-glass opacity in both lungs. NTM suspected of RGM was isolated from the blood cultures. During hospitalization, multiple erythematous and hemorrhagic crusted nodules developed on the patient’s upper and lower extremities, which were confirmed as disseminated NTM infection on skin biopsy.

Interventions:
After NTM suspected of RGM was isolated from the blood cultures, the patient was empirically treated with antibiotics used for NTM infection, and the PICC was removed. Thereafter, the subspecies of NTM was reported as M massiliense and she was treated according to the antibiotic susceptibility testing results.

Outcome:
Although skin lesions and inflammatory markers improved gradually during antibiotic treatment over 10 weeks, NTM could still be isolated from the blood culture.

Lessons:
Disseminated NTM infections with RGM bacteremia in an immunocompetent host have rarely been reported. In this case, PICC placement for more than 6 months was suspected to be an important risk factor for RGM bacteremia in an immunocompetent patient. To date, there are only insufficient case reports, moreover no clear guidelines regarding the optimal choice of antibiotics or length of treatment for disseminated NTM infection. Therefore, it is necessary to establish treatment guidelines for patients with disseminated NTM infection and bacteremia.
Effect of educational music intervention on college students’ aggressive behaviour
Authors: Nwokenna Edith N. , Sewagegn Abatihun Alehegn , Falade Temitope Ayodeji 
Published: January 2023

Background:
Students’ aggressive behavior and its negative implications have continued to intrigue researchers. Thus, the present study examined the effect of educational music intervention in reducing aggressive behavior among college students.

Method:
Quantitative data were collected from 30 college student participants in the treatment group and 30 college student participants in the control group using the teacher-rating of students’ aggressive behaviors and self-rated aggression scale instruments. This study adopted the IBM SPSS version 25 program and JASP statistical program for data analysis.

Results:
The result of the study indicated that college students in the educational music group showed considerable mean decline in aggressive behavior at posttest compared to their counterparts in the control group. At follow-up, it was revealed that educational music intervention consistently reduced the college students’ aggressive behavior.

Conclusion:
Educational music intervention proved to be a helpful intervention in reducing Nigerian college students’ aggressive behavior. In light of this, it would be beneficial to implement educational music intervention to reduce aggressive behavior among college students in other localities.
The efficacy and safety of Shenfu injection in patients undergoing percutaneous coronary intervention for ST segment elevation myocardial infarction: A protocol for systematic review and meta-analysis
Authors: Yan Xiafeng , Dong Minya , Qin Xiao , Li Nannan , Li Na 
Published: January 2023

Background:
Shenfu injection is a traditional Chinese medicine formulation that alleviates ischemia–reperfusion injury through multiple pharmacologic effects. However, there is lack of evidence regarding its efficacy in myocardial infarction. We performed a protocol for systematic review and meta-analysis to evaluate the efficacy and safety of Shenfu injection for ST segment elevation myocardial infarction after primary percutaneous coronary intervention.

Methods:
This review has been reported following the preferred reporting items for systematic reviews and meta-analyses protocol. A literature search was performed in November 2022 without restriction to regions, publication types, or languages. The primary sources were the electronic databases of PubMed, Embase, Web of Science, the Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure database, Chinese Biomedical Database, and Chinese Science and Technology Periodical database. Risk of bias will be assessed according to the Cochrane Risk of Bias Tool. Data analysis was performed using Reviewer Manager 5.4.

Results:
The results of this systematic review will be published in a peer-reviewed journal.

Conclusion:
This systematic review will provide evidence to judge whether Shenfu injection is effective and safe in patients undergoing percutaneous coronary intervention for ST segment elevation myocardial infarction.