bluuebunny/crossref_metadata_2025_split huggingface dataset:
Busulfan Interlaboratory Proficiency Testing Program Revealed Worldwide Errors in Drug Quantitation and Dose Recommendations
Authors: Kweekel Dina M. , McCune Jeannine S. , Punt Arjen M. , van Luin Matthijs , Franssen Eric J.F. 
Published: May 2023

Background:
The clinical outcomes of busulfan-based conditioning regimens for hematopoietic cell transplantation (HCT) have been improved by personalizing the doses to target narrow busulfan plasma exposure. An interlaboratory proficiency test program for the quantitation, pharmacokinetic modeling, and busulfan dosing in plasma was developed. Previous proficiency rounds (ie, the first 2) found that 67%–85% and 71%–88% of the dose recommendations were inaccurate, respectively.

Methods:
A proficiency test scheme was developed by the Dutch Foundation for Quality Assessment in Medical Laboratories (SKML) and consisted of 2 rounds per year, with each round containing 2 busulfan samples. In this study, 5 subsequent proficiency tests were evaluated. In each round, the participating laboratories reported their results for 2 proficiency samples (ie, low and high busulfan concentrations) and a theoretical case assessing their pharmacokinetic modeling and dose recommendations. Descriptive statistics were performed, with ±15% for busulfan concentrations and ±10% for busulfan plasma exposure. The dose recommendations were deemed accurate.

Results:
Since January 2020, 41 laboratories have participated in at least 1 round of this proficiency test. Over the 5 rounds, an average of 78% of the busulfan concentrations were accurate. Area under the concentration–time curve calculations were accurate in 75%–80% of the cases, whereas only 60%–69% of the dose recommendations were accurate. Compared with the first 2 proficiency test rounds (PMID 33675302, October, 2021), the busulfan quantitation results were similar, but the dose recommendations worsened. Some laboratories repeatedly submit results that deviated by more than 15% from the reference values.

Conclusions:
The proficiency test showed persistent inaccuracies in busulfan quantitation, pharmacokinetic modeling, and dose recommendations. Additional educational efforts have yet to be implemented; regulatory efforts seem to be needed. The use of specialized busulfan pharmacokinetic laboratories or a sufficient performance in busulfan proficiency tests should be required for HCT centers that prescribe busulfan.
A classifier based on 273 urinary peptides predicts early renal damage in primary hypertension
Authors: Lin Lirong , Wang Chunxuan , Ren Jiangwen , Mei Mei , Zheng Luquan , Yang Jurong 
Published: May 2023

Objectives:
Renal diseases caused by primary hypertension (HTN) are often asymptomatic without sensitive markers for early diagnosis and prediction, easily progressing to severe and irreversible renal damage in patients with clinical manifestations. This study explored whether a classifier developed based on 273 urinary peptides (CKD273) could serve as a potential biomarker for early prediction of renal damage in HTN.

Methods:
Urinary CKD273 level of healthy individuals, HTN + normoalbuminuric and HTN + albuminuria patients were compared, and 22 baseline data including sex, age, renal function, and hypertensive fundus lesions were collected. Patients diagnosed with HTN, albuminuria, and normal renal function were followed up. According to the follow-up results, the cut-off value of CKD273 in predicting hypertensive renal injury was calculated and analyzed in the high-risk and low-risk groups of HTN patients for its performance in detecting early hypertensive renal injury.

Results:
Among a sum of 319 participants, average urinary CKD273 level was significantly higher in patients with HTN than in normal individuals. A total of 147 HTN patients with normal albuminuria were followed up for a mean of 3.8 years. Thirty-five patients showed urinary albumin-to-creatinine ratio (uACR) at least 30 mg/g for three consecutive times. The receiver-operating characteristic (ROC) curve showed that the urinary CKD273 cut-off value for evaluating new-onset proteinuria in patients with HTN was 0.097. Based on this cut-off value, 39 and 108 patients were included in the high-risk and low-risk groups, respectively. Specifically, compared with patients in the low-risk group, those in the high-risk group showed significantly longer duration of HTN, higher proportions of hypertensive fundus lesions and at least 30 mg/g uACR, and higher levels of homocysteine (Hcy), cystatin C (CysC), beta-2 microglobulin (β2-MG), and uACR. 76.9% of high-risk patients had significantly higher new-onset proteinuria than the low-risk group. Correlation analysis demonstrated a positive correlation between urinary CKD273 and UACR (r = 0.494, P = 0.000). The incidence of new-onset albuminuria was significantly higher in the high-risk group than in the low-risk group, as shown by Cox regression analysis. The areas under the curve of CKD273, Hcy, β2-MG, and CysC were 0.925, 0.753, 0.796, and 0.769, respectively.

Conclusion:
Urinary CKD273 is a predictor of new-onset proteinuria in patients with HTN, therefore, it can be used for diagnosing patients with early renal injury in patients with HTN, contributing to early prevention and treatment of hypertensive nephropathy.
A Novel Combination of Host Protein Biomarkers to Distinguish Bacterial From Viral Infections in Febrile Children in Emergency Care
Authors: Tan Chantal D. , van den Broek Bryan , Womersley Rebecca S. , Kaforou Myrsini , Hagedoorn Nienke N. , van der Flier Michiel , Jackson Heather , Moll Henriette A. , Snijder Rozemarijn , de Jonge Marien I. , Vermont Clementien L. ,   On behalf of PERFORM Consortium
Published: May 2023

Background:
Distinguishing bacterial and viral infections based on clinical symptoms in febrile children attending the emergency department (ED) is challenging. The aim of this study is to determine a novel combination of host protein biomarkers and to assess its performance in distinguishing between bacterial and viral infection in febrile children attending EDs.

Methods:
A literature search was performed to identify blood protein biomarkers able to distinguish bacterial and viral infections (May 2015–May 2019). We selected 7 protein biomarkers: Procalcitonin, TNF-related apoptosis-inducing ligand (TRAIL), interleukin (IL)-4, IL-6, Interferon gamma-induced protein-10 (CXCL-10), interferon-gamma and lipocalin 2 (LCN2). These were measured in blood plasma using a bead-based immunoassay in children with a confirmed bacterial or viral infection attending EDs in the Netherlands. We used generalized linear modeling to classify bacterial and viral infections and applied a previously developed feature selection algorithm to select the optimal combination of proteins. We performed a subgroup analysis of this protein signature in patients with C-reactive protein <60 mg/L, representing a clinically challenging diagnostic group.

Results:
In total 102 children were included (N = 67 bacterial; N = 35 viral). Individual performance of the 7 biomarkers in classifying bacterial versus viral infections ranged from 60.8%–74.5% area under the receiver operator curve (AUC). TRAIL, LCN2 and IL-6 were identified as the best 3-protein signature with an AUC of 86% (95% CI: 71.3%–100%). In 57 patients with C-reactive protein levels <60 mg/L, the 3-protein signature had an AUC of 85.1% (95% CI: 75.3%–94.9%).

Conclusion:
We demonstrate a promising novel combination of 3 host protein biomarkers; TRAIL, LCN2 and IL-6, which performs well in classifying bacterial and viral infections in febrile children in emergency care.
“Go With the Flow”: A Qualitative Description of Infant Feeding Experiences Among Women With HIV in the United States
Authors: Pagano-Therrien Jesica , Griswold Michele K. , Amoah Rita K. 
Published: May 2023

Abstract
Breastfeeding affords numerous health benefits to mothers and children, but for women with HIV in the United States, avoidance of breastfeeding is recommended. Evidence from low-income countries demonstrates low risk of HIV transmission during breastfeeding with antiretroviral therapy, and the World Health Organization recommends exclusive breastfeeding and shared decision making about infant feeding options in low-income and middle-income countries. In the United States, gaps in knowledge exist surrounding the experiences, beliefs, and feelings of women with HIV surrounding infant feeding decisions. Undergirded by a framework of person-centered care, this study describes the experiences, beliefs, and feelings of women with HIV in the United States surrounding recommendations for breastfeeding avoidance. Although no participants reported consideration of breastfeeding, multiple gaps were identified with implications for the clinical care and counseling of the mother–infant dyad.
Nocturnal Vulval Pain in Girls—A Subset of Vulvodynia?
Authors: Sagoo Manpreet K. , Lakhan Manpreet , Moyal-Barracco Micheline , Lewis Fiona M. 
Published: May 2023

Objectives
The aims of the authors’ case series were to outline the clinical features of prepubertal nocturnal vulval pain syndrome and to look at management and outcomes.

Methods
Clinical details of prepubertal girls experiencing episodes of nocturnal vulval pain with no identifiable cause were recorded and analyzed. Parents completed a questionnaire to look at outcomes.

Results
Eight girls with age at onset of symptoms between 3.5 and 8 years (mean 4.4 years) were included. Each patient described intermittent episodes of vulval pain lasting between 20 minutes and 5 hours, starting 1–4 hours after falling asleep. They were crying and rubbing or holding the vulva with no obvious cause seen. Many were not fully awake and 75% had no recollection of the events. Management focused on reassurance alone. The questionnaire showed that 83% had full resolution of symptoms with a mean duration of 5.7 years.

Conclusions
Prepubertal nocturnal vulval pain syndrome may be a subset of vulvodynia (generalized, spontaneous, intermittent) to be included in the clinical spectrum of night terrors. Recognizing the clinical key features should aid prompt diagnosis and reassurance of the parents.
Probiotic modulation of gut microbiota by Bacillus coagulans MTCC 5856 in healthy subjects: A randomized, double-blind, placebo-control study
Authors: Majeed Muhammed , Nagabhushanam Kalyanam , Mundkur Lakshmi , Paulose Shaji , Divakar Hema , Rao Sudha , Arumugam Sivakumar 
Published: May 2023

Background:
Probiotics are known to rebalance the gut microbiota in dysbiotic individuals, but their impact on the gut microbiome of healthy individuals is seldom studied. The current study is designed to assess the impact and safety of Bacillus coagulans (Weizmannia coagulans) microbial type culture collection 5856 (LactoSpore®) supplementation on microbiota composition in healthy Indian adults.

Methods:
The study participants (N = 30) received either LactoSpore (2 billion colony-forming units/capsule) or placebo for 28 days. The general and digestive health were assessed through questionnaires and safety by monitoring adverse events. Taxonomic profiling of the fecal samples was carried out by 16S rRNA amplicon sequencing using the Illumina MiSeq platform. The bacterial persistence was enumerated by quantitative reverse transcription-polymerase chain reaction.

Results:
Gut health, general health, and blood biochemical parameters remained normal in all the participants. No adverse events were reported during the study. Metataxonomic analysis revealed minimal changes to the gut microbiome of otherwise healthy subjects and balance of Bacteroidetes and Firmicutes was maintained by LactoSpore. The relative abundance of beneficial bacteria like Prevotella, Faecalibacterium, Blautia, Megasphaera, and Ruminococcus showed an increase in probiotic-supplemented individuals. The quantitative polymerase chain reaction analysis revealed highly variable numbers of B. coagulans in feces before and after the study.

Conclusion:
The present study results suggest that LactoSpore is safe for consumption and does not alter the gut microbiome of healthy individuals. Minor changes in a few bacterial species may have a beneficial outcome in healthy individuals. The results reiterate the safety of B. coagulans microbial type culture collection 5856 as a dietary supplement and provide a rationale to explore its effect on gut microbiome composition in individuals with dysbiosis.
PAX5 fusion genes in acute lymphoblastic leukemia: A literature review
Authors: Fouad Fatma Mohamed , Eid Jehane I. 
Published: May 2023

Acute lymphoblastic leukemia (ALL) is a common cancer affecting children worldwide. The development of ALL is driven by several genes, some of which can be targeted for treatment by inhibiting gene fusions. PAX5 is frequently mutated in ALL and is involved in chromosomal rearrangements and translocations. Mutations in PAX5 interact with other genes, such as ETV6 and FOXP1, which influence B-cell development. PAX5/ETV6 has been observed in both B-ALL patients and a mouse model. The interaction between PAX5 and FOXP1 negatively suppresses the Pax5 gene in B-ALL patients.
Additionally, ELN and PML genes have been found to fuse with PAX5, leading to adverse effects on B-cell differentiation. ELN-PAX5 interaction results in the decreased expression of LEF1, MB1, and BLNK, while PML-PAX5 is critical in the early stages of leukemia. PAX5 fusion genes prevent the transcription of the PAX5 gene, making it an essential target gene for the study of leukemia progression and the diagnosis of B-ALL.
Veterans' Experiences of Support in Managing Comorbid Sleep Apnea and Type 2 Diabetes
Authors: Song Yeonsu , Choi Sarah E. , Papazyan Anna , Macey Paul M. , Alessi Cathy A. , Fung Constance H. , Josephson Karen R. , Martin Jennifer L. 
Published: May 2023

Background
Obstructive sleep apnea (OSA) is highly prevalent in patients with Type 2 diabetes, more so in veterans compared with nonveterans. Positive airway pressure is the recommended first-line treatment for OSA. However, adherence to both positive airway pressure and diabetes management regimens can be challenging for older adults. Support from family or friends may improve glucose control or sleep-apnea-related symptoms, yet the evidence is limited when both conditions coexist.

Objectives
This study aimed to describe veterans' experiences of support from family and friends with managing comorbid sleep apnea and Type 2 diabetes.

Methods
We conducted a postal survey of older veterans with OSA and Type 2 diabetes from one healthcare system. Questions include demographic and health-related information, information about sleep apnea and diabetes treatment and education received, related support from family or a friend, perceived benefits of regular positive airway pressure device use on improving sleep health, and perceived benefits of education for family or a friend on sleep apnea and diabetes. Descriptive and bivariate analyses were performed.

Results
Of 145 respondents (mean age = 72 years), 43% reported receiving help for Type 2 diabetes from family or a friend. Almost two thirds of the respondents were currently using a positive airway pressure device, of whom 27% received support with device use from family or friends. About one third of veterans perceived family and friends receiving education on treating sleep apnea and diabetes to be very or extremely helpful. Such perceived benefit was higher among those who were married or identified as non-White. Veterans using a positive airway pressure device had lower hemoglobin A1c levels than nonusers.

Discussion
Veterans perceived that additional education for the individuals providing support would be beneficial. Future studies could address interventions to increase sleep apnea and Type 2 diabetes knowledge among families and friends of veterans with these comorbid conditions. In addition, patients' adherence to positive airway pressure may be enhanced by support from family and friends.
Overview of the Health Communication Curriculum in Canadian Master of Public Health Programs
Authors: MacKay Melissa , Li Yan , Papadopoulos Andrew , McWhirter Jennifer E. 
Published: May 2023

Context:
Competency-based public health education ensures practitioners are well equipped to positively influence the health of the public. The Public Health Agency of Canada's Core Competencies for Public Health has named communication as an essential competency area for practitioners. However, little is known about how Master of Public Health (MPH) programs in Canada support trainees in developing the recommended core competencies in communication.

Objective:
Our research aims to provide an overview of the extent to which communication is embedded in the curriculum of MPH programs in Canada.

Design:
We conducted an online scan of Canadian MPH course titles and descriptions to determine how many MPH programs offer communication-focused courses (ie, health communication), knowledge mobilization courses (eg, knowledge translation), and other courses that may support communication skills. Two researchers coded the data; discrepancies were resolved via discussion.

Results:
Of the 19 MPH programs in Canada, less than half (n = 9) offer courses specifically focused on communication (ie, health communication); these courses are mandatory in only 4 programs. Seven programs offer knowledge mobilization courses; none are mandatory. Sixteen MPH programs offer a total of 63 other public health courses that are not focused on communication but contain communication terms (eg, marketing, literacy) in their course descriptions. No Canadian MPH program has a communication-focused stream or option.

Conclusion:
Canadian-trained MPH graduates may not be receiving sufficient communication training to equip them for effective and precise public health practice. This is particularly concerning, given that current events have underlined the importance of health, risk, and crisis communication.
Impulsivity in Depression: Its Relation to Suicidality
Authors: Öğüt Çağri , Başar Koray , Karahan SEVİLAY 
Published: May 2023

Objective:
Impulsivity is an important risk for suicidality, which is common in patients with major depressive disorder (MDD). The goal of this study was to examine multiple facets of impulsivity in depressed patients compared with healthy controls and to assess their relationship to suicidality.

Method:
Outpatients diagnosed with MDD using the Structured Clinical Interview for DSM-IV were recruited. Two groups were constituted as “MDD in remission” (n=32) and “MDD” (n=71). The “healthy control” group (n=30) consisted of individuals who had never been diagnosed with any psychiatric disorder. Impulsivity was assessed with the Barratt Impulsivity Scale (BIS), a self-rating measure, and with the following behavioral tasks: Go/No-go Task, Iowa Gambling Task, and Balloon Analogue Risk Task. The scores of the 3 groups (n=133) were compared to evaluate the effect of MDD. The scores were also analyzed and compared in the patients in the 2 MDD groups (n=103) with respect to their current and lifetime suicidality.

Results:
There was no difference in the 3 groups in task scores, but nonplanning BIS was correlated with the severity of depressive symptoms. Patients with suicidal ideation (SI) had higher BIS total and attention impulsivity scores and more commission errors on the Go/No-go Task, reflecting failure in response inhibition, compared with the patients without SI.

Conclusions:
Failure to show differences in impulsivity-related tasks suggests that there might be no relationship between the state of depression and impulsivity. However, these findings confirm that there is an association between SI and response inhibition and the attention facet of impulsivity in depression.
Antidepressant Strategies for Treatment of Acute Depressive Episodes Among Veterans
Authors: Shiroma Paulo R. , Thuras Paul , Atkinson David M. , Baltutis Eric , Bloch Martin , Westanmo Anders 
Published: May 2023

Objective:
The 2016 VA/DoD Clinical Practice Guideline for Management of Major Depressive Disorder offers consensus-based recommendations when response to the initial antidepressant medication is suboptimal; however, little is known about “real-world” pharmacological strategies used by providers treating depression in the Veterans Affairs Health Care System (VAHCS).

Methods:
We extracted pharmacy and administrative records of patients diagnosed with a depressive disorder and treated at the Minneapolis VAHCS between January 1, 2010 and May 11, 2021. Patients with bipolar disorder, psychosis-spectrum, or dementia diagnoses were excluded. An algorithm was developed to identify antidepressant strategies: monotherapy (MONO); optimization (OPM); switching (SWT); combination (COM); and augmentation (AUG). Additional data extracted included demographics, service utilization, other psychiatric diagnoses, and clinical risk for hospitalization and mortality.

Results:
The sample consisted of 1298 patients, 11.3% of whom were female. The mean age of the sample was 51 years. Half of the patients received MONO, with 40% of those patients receiving inadequate doses. OPM was the most common next-step strategy. SWT and COM/AUG were used for 15.9% and 2.6% of patients, respectively. Overall, patients who received COM/AUG were younger. OPM, SWT, and COM/AUG occurred more frequently in psychiatric services settings and required a greater number of outpatient visits. The association between antidepressant strategies and risk of mortality became nonsignificant after accounting for age.

Conclusions:
Most of the veterans with acute depression were treated with a single antidepressant, while COM and AUG were rarely used. The age of the patient, and not necessarily greater medical risks, appeared to be a major factor in decisions about antidepressant strategies. Future studies should evaluate whether implementation of underutilized COM and AUG strategies early in the course of depression treatment are feasible.
Evaluation of Conflict of Interest in Consulting Fee Payments in Plastic Surgery and Related Specialties
Authors: Summerville Lesley , Boas Samuel R , Wee Corinne , Isbester Kelsey , Kumar Anand 
Published: May 2023

Background:
The Physician Payments Sunshine Act (PPSA) was enacted to increase transparency regarding physician and industry financial interests. Consulting fee payments comprise a large proportion of these financial relationships. We hypothesized that there are discrepancies amongst industry-derived consulting payments to medical and surgical specialties. The purpose of this study was to evaluate the distribution of consulting fee payments to plastic surgery and related specialties.

Methods:
This cross-sectional study utilized the publicly available CMS Open Payments Program database for 2018. Consulting fee payments to physicians practicing in dermatology, internal medicine, neurosurgery, orthopedic surgery, otolaryngology, and plastic surgery were isolated and analyzed to identify discrepancies in consulting payments among these specialties and within plastic surgery.

Results:
A total of $250,518,240 was paid in consulting fees to specialties analyzed, with the largest average payment made to orthopedic surgeons and neurosurgeons. Nearly half of physicians were paid at least $5,000 for consulting fees in 2018. Most payments were not associated with contextual information. Among US plastic surgeons, 4.2% held financial relationships with corporations and were likely to be paid more when consulting for small companies.

Conclusions:
Consulting payments make up a large proportion of payments included in the Open Payments Database. While gender, state, company type, and sole proprietorship did not correlate with higher pay, plastic surgeons who consulted for small companies were paid more per payment than those working for large companies (Figure 1). Future studies are warranted to determine if these industry financial relationships impact physician behavior.