bluuebunny/crossref_metadata_2025_split huggingface dataset:
Requirements for operational cure in multiple myeloma
Authors: Mohty Mohamad , Avet-Loiseau Hervé , Harousseau Jean-Luc 
Published: July 2021

Abstract
Multiple myeloma is usually considered an incurable disease. However, with the therapeutic improvement observed in the past few years, achievement of an operational cure is increasingly becoming a realistic goal. The advent of novel agents, with or without high-dose chemotherapy or autologous transplantation, revealed a correlation between depth of response to treatment and outcome. Of note, minimal residual disease (MRD) negativity has been shown to be associated with improved progression-free survival (PFS), and MRD status is becoming a well-established and strong prognostic factor. Here, we discuss the impact of MRD negativity on PFS and long-term disease control, as a surrogate for potential cure in a significant proportion of patients. MRD value and impact should be examined by focusing on different parameters: (1) sensitivity or lower limit of detection level (method used), (2) timing of assessment and sustainability, (3) type and duration of treatment, (4) initial prognostic factors (most importantly cytogenetics), and (5) patient age. Currently, the highest probability of operational cure is in younger patients receiving the most active drugs, in combination with autologous transplantation followed by maintenance therapy. Older patients are also likely to achieve operational cure, especially if they are treated upfront with anti-CD38 antibody–based therapy but also with novel immunotherapies in future protocols. Incorporation of MRD as a surrogate end point in clinical trials would enable shorter trials, leading to more personalized management and achievement of long-term cure.
Simulation studies to optimize genomic selection in honey bees
Authors: Bernstein Richard , Du Manuel , Hoppe Andreas , Bienefeld Kaspar 
Published: July 2021

Abstract
Background
With the completion of a single nucleotide polymorphism (SNP) chip for honey bees, the technical basis of genomic selection is laid. However, for its application in practice, methods to estimate genomic breeding values need to be adapted to the specificities of the genetics and breeding infrastructure of this species. Drone-producing queens (DPQ) are used for mating control, and usually, they head non-phenotyped colonies that will be placed on mating stations. Breeding queens (BQ) head colonies that are intended to be phenotyped and used to produce new queens. Our aim was to evaluate different breeding program designs for the initiation of genomic selection in honey bees.

Methods
Stochastic simulations were conducted to evaluate the quality of the estimated breeding values. We developed a variation of the genomic relationship matrix to include genotypes of DPQ and tested different sizes of the reference population. The results were used to estimate genetic gain in the initial selection cycle of a genomic breeding program. This program was run over six years, and different numbers of genotyped queens per year were considered. Resources could be allocated to increase the reference population, or to perform genomic preselection of BQ and/or DPQ.

Results
Including the genotypes of 5000 phenotyped BQ increased the accuracy of predictions of breeding values by up to 173%, depending on the size of the reference population and the trait considered. To initiate a breeding program, genotyping a minimum number of 1000 queens per year is required. In this case, genetic gain was highest when genomic preselection of DPQ was coupled with the genotyping of 10–20% of the phenotyped BQ. For maximum genetic gain per used genotype, more than 2500 genotyped queens per year and preselection of all BQ and DPQ are required.

Conclusions
This study shows that the first priority in a breeding program is to genotype phenotyped BQ to obtain a sufficiently large reference population, which allows successful genomic preselection of queens. To maximize genetic gain, DPQ should be preselected, and their genotypes included in the genomic relationship matrix. We suggest, that the developed methods for genomic prediction are suitable for implementation in genomic honey bee breeding programs.
Comparative transcriptome analysis reveals regulatory network and regulators associated with proanthocyanidin accumulation in persimmon
Authors: Zheng Qingyou , Chen Wenxing , Luo Man , Xu Liqing , Zhang Qinglin , Luo Zhengrong 
Published: July 2021

Abstract
Background
Proanthocyanidins (PAs) are important plant secondary metabolites that confer flavor, nutritional value, and resistance to pathogens. Persimmon is one of the PA richest crops. Mature fruits can be inedible because of the astringency caused by high PA levels and need to go through a de-astringency treatment before consumption. The molecular basis for PA accumulation is poorly known, particularly transcriptional regulators. We characterised three genotypes (‘Luotiantianshi’ (LT), ‘Mopanshi’ (MP), and ‘Youhou’ (YH)) with different PA accumulation patterns using an approach that combined PacBio full-length sequencing and Illumina-based RNA sequencing to build high-quality full-length transcriptomes. Additionally, we analysed transcriptome dynamics of the three genotypes (LT, MP, and YH) at four key fruit developmental stages.

Results
A total of 96,463 transcripts were obtained. We identified 80,075 protein-coding sequences (CDSs), 71,137 simple sequence repeats (SSRs), and 27,845 long noncoding RNAs (lncRNAs). Pearson correlation coefficient (PCC), principal component analysis (PCA), and differentially expressed transcripts (DETs) analyses indicated that the four different developmental stages within a genotype exhibited similar transcriptome activities. A total of 2,164 transcripts specific to each fruit developmental stage were detected. The transcripts specific to early stages were attributed to phenylpropanoid and flavonoid biosynthesis. Co-expression network analyses revealed MEbrown and MEblue modules were strongly associated to PA accumulation. From these two modules, 20 hub TFs are potential regulators for PA accumulation. Among them, Cluster_78388 (SBP protein), Cluster_63454 (bZIP protein), and Cluster_66595 (MYB protein) appear to involve in the PA biosynthesis in Chinese genotypes.

Conclusions
This is the first high-quality reference transcriptome for commercial persimmon. Our work provides insights into the molecular pathways underlying PA accumulation and enhances our global understanding of transcriptome dynamics throughout fruit development.
Liver injury caused by fenofibrate within 48 h after first administration: a case report
Authors: He Yu , Qin Ming-zhao , Chen Yi-wen 
Published: July 2021

Abstract
Background
Fenofibrate is commonly used in the treatment of dyslipidemia. Fenofibrate is related to mild aminotransferase elevations and in some cases severe chronic injury such as fibrosis or cirrhosis, resulting in liver transplantation or death. The latency of disease has been reported to range between weeks to years.

Case presentation
A 63 years old male with hypertriglyceridemia developed symptoms of fatigue and anorexia 48 h after taking fenofibrate for the first time. The patient’s aminotransferase level was more than 10 times ULN. Immediately, fenofibrate was discontinued and aminotransferase level returned to normal 23 days later. To assess causality between the drug and liver damage, the standardized Roussel Uclaf Causality Assessment Method (RUCAM) was used. The patient's RUCAM score was 7, which fell in the group of “probable”. Eight months later, follow-up examination suggested the liver function was normal.

Conclusions
Weakness, fatigue and abnormal liver function during fenofibrate therapy should be closely monitored and trigger prompt withdrawal if these symptoms occur.
Role of handgrip strength in predicting new-onset diabetes: findings from the survey of health, ageing and retirement in Europe
Authors: Li Guochen , Qiao Yanan , Lu Yanqiang , Liu Siyuan , Ding Yi , Chen Xing , Ke Chaofu 
Published: July 2021

AbstractBackgroundDiabetes is a major concern for the global health burden. This study aimed to investigate the relationship between handgrip strength (HGS) and the risk of new-onset diabetes and to compare the predictive abilities between relative HGS and dominant HGS.MethodsThis longitudinal study used data from the Survey of Health, Ageing and Retirement in Europe (SHARE), including 66,100 European participants aged 50 years or older free of diabetes at baseline. The Cox proportional hazard model was used to analyze the relationship between HGS and diabetes, and the Harrell’s C index, net reclassification index (NRI), and integrated discrimination improvement (IDI) were calculated to evaluate the predictive abilities of different HGS expressions.ResultsThere were 5,661 diabetes events occurred during follow-up. Compared with individuals with lowest quartiles, the hazard ratios (95 % confidence intervals) of the 2nd-4th quartiles were 0.88 (0.81–0.94), 0.82 (0.76–0.89) and 0.85 (0.78–0.93) for dominant HGS, and 0.95 (0.88–1.02), 0.82 (0.76–0.89) and 0.60 (0.54–0.67) for relative HGS. After adding dominant HGS to an office-based risk score (including age, gender, body mass index, smoking, and hypertension), the incremental values of the Harrell’s C index, NRI, IDI of relative HGS were all slightly higher than those of dominant HGS in both training and validation sets.ConclusionsOur findings supported that HGS was an independent predictor of new-onset diabetes in the middle-aged and older European population. Moreover, relative HGS exhibited a slightly higher predictive ability than dominant HGS.
Achieved blood pressure post-acute kidney injury and risk of adverse outcomes after AKI: A prospective parallel cohort study
Authors: McCoy Ian , Brar Sandeep , Liu Kathleen D. , Go Alan S. , Hsu Raymond K. , Chinchilli Vernon M. , Coca Steven G. , Garg Amit X. , Himmelfarb Jonathan , Ikizler T. Alp , Kaufman James , Kimmel Paul L. , Lewis Julie B. , Parikh Chirag R. , Siew Edward D. , Ware Lorraine B. , Zeng Hui , Hsu Chi-yuan ,   for the Assessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury (ASSESS-AKI) study investigators
Published: July 2021

Abstract
Background
There has recently been considerable interest in better understanding how blood pressure should be managed after an episode of hospitalized AKI, but there are scant data regarding the associations between blood pressure measured after AKI and subsequent adverse outcomes. We hypothesized that among AKI survivors, higher blood pressure measured three months after hospital discharge would be associated with worse outcomes. We also hypothesized these associations between blood pressure and outcomes would be similar among those who survived non-AKI hospitalizations.

Methods
We quantified how systolic blood pressure (SBP) observed three months after hospital discharge was associated with risks of subsequent hospitalized AKI, loss of kidney function, mortality, and heart failure events among 769 patients in the prospective ASSESS-AKI cohort study who had hospitalized AKI. We repeated this analysis among the 769 matched non-AKI ASSESS-AKI enrollees. We then formally tested for AKI interaction in the full cohort of 1538 patients to determine if these associations differed among those who did and did not experience AKI during the index hospitalization.

Results
Among 769 patients with AKI, 42 % had subsequent AKI, 13 % had loss of kidney function, 27 % died, and 18 % had heart failure events. SBP 3 months post-hospitalization did not have a stepwise association with the risk of subsequent AKI, loss of kidney function, mortality, or heart failure events. Among the 769 without AKI, there was also no stepwise association with these risks. In formal interaction testing using the full cohort of 1538 patients, hospitalized AKI did not modify the association between post-discharge SBP and subsequent risks of adverse clinical outcomes.

Conclusions
Contrary to our first hypothesis, we did not observe that higher stepwise blood pressure measured three months after hospital discharge with AKI was associated with worse outcomes. Our data were consistent with our second hypothesis that the association between blood pressure measured three months after hospital discharge and outcomes among AKI survivors is similar to that observed among those who survived non-AKI hospitalizations.
Overtreatment in nonmalignant lesions detected in a colorectal cancer screening program: a retrospective cohort study
Authors: Cubiella Joaquín , González Antía , Almazán Raquel , Rodríguez-Camacho Elena , Zubizarreta Raquel , Peña-Rey Lorenzo Isabel 
Published: July 2021

Abstract
Background
Although colorectal cancer (CRC) screening programs reduce CRC incidence and mortality, they are associated with risks in healthy subjects. However, the risk of overtreatment and overdiagnosis has not been determined yet. The aim of this study was to report the surgery rates in patients with nonmalignant lesions detected within the first round of a fecal immunochemical test (FIT) based CRC screening program and the factors associated with it.

Methods
We included in this analysis all patients with nonmalignant lesions detected between May 2013 and June 2019 in the Galician (Spain) CRC screening program. We calculated surgery rate according to demographic variables, the risk classification according to the colonoscopy findings (European guidelines for quality assurance), the endoscopist’s adenoma detection rate (ADR) classified into quartiles and the hospital’s complexity level. We determined which variables were independently associated with surgery rate and expressed the association as Odds Ratio and its 95% confidence interval (CI).

Results
We included 15,707 patients in the analysis with high (19.9%), intermediate (26.9%) low risk (23.3%) adenomas and normal colonoscopy (29.9%) detected in the analyzed period. Colorectal surgery was performed in 162 patients (1.03, 95% CI 0.87–1.19), due to colonoscopy complications (0.02, 95% CI 0.00–0.05) and resection of colorectal benign lesions (1.00, 95% CI 0.85–1.16). Median hospital stay was 6 days with 17.3% patients developing minor complications, 7.4% major complications and one death. After discharge, complications developed in 18.4% patients. In benign lesions, an endoscopic resection was performed in 25.4% and a residual premalignant lesion was detected in 89.9%. The variables independently associated with surgery in the multivariable analysis were age (≥60 years = 1.57, 95% CI 1.11–2.23), sex (female = 2.10, 95% CI 1.52–2.91), the European guidelines classification (high risk = 67.94, 95% CI 24.87–185.59; intermediate risk = 5.63, 95% CI 1.89–16.80; low risk = 1.43; 95% CI 0.36–5.75), the endoscopist’s ADR (Q4 = 0.44, 95% CI 0.28–0.68; Q3 = 0.44, 95% CI 0.27–0.71; Q2 = 0.71, 95% CI 0.44–1.14) and the hospital (tertiary = 0.54, 95% CI 0.38–0.79).

Conclusions
In a CRC screening program, the surgery rate and the associated complications in patients with nonmalignant lesions are low, and related to age, sex, endoscopic findings, endoscopist’s ADR and the hospital’s complexity.
Ethnic variation in medial orbital wall anatomy and its implications for decompression surgery
Authors: Chan Minhui Amy , Ibrahim Farah , Kumaran Arjunan , Yong Kailing , Chan Anita Sook Yee , Shen Sunny 
Published: July 2021

Abstract
Background
To describe the inter-ethnic variation in medial orbital wall anatomy between Chinese, Malay, Indian and Caucasian subjects.

Methods
Single-centre, retrospective, Computed Tomography (CT)-based observational study. 20 subjects of each ethnicity, were matched for gender and laterality. We excluded subjects younger than 16 years and those with orbital pathology. OsiriX version 8.5.1 (Pixmeo., Switzerland) and DICOM image viewing software CARESTREAM Vue PACS (Carestream Health Inc., USA) were used to measure the ethmoidal sinus length, width and volume, medial orbital wall and floor angle and the relative position of the posterior ethmoid sinus to the posterior maxillary wall. Statistical analyses were performed using Statistical Package for Social Sciences version 25.0 (IBM, USA).

Results
There were 12 males (60 %) in each group, with no significant difference in age (p = 0.334–0.994). The mean ethmoid sinus length in Chinese, Malay, Indian and Caucasian subjects, using the Chinese as reference, were 37.2, 36.9, 38.0 and 37.4mm, the mean width was 11.6, 10.5, 11.4 and 10.0mm (p = 0.020) and the mean ethmoid sinus volume were 3362, 3652, 3349 and 3898mm3 respectively. The mean medial orbital wall and floor angle was 135.0, 131.4, 131.0 and 136.8 degrees and the mean relative position of posterior ethmoid sinus to posterior maxillary wall were − 2.0, -0.2, -1.5 and 1.6mm (p = 0.003) respectively.

Conclusions
No inter-ethnic variation was found in decompressible ethmoid sinus volume. Caucasians had their posterior maxillary sinus wall anterior to their posterior ethmoidal walls unlike the Chinese, Malay and Indians. Awareness of ethnic variation is essential for safe orbital decompression.
Effects of backhand stroke styles on bone mineral content and density in postmenopausal recreational tennis players: a cross-sectional pilot investigation
Authors: Wang Ho-Seng , Tsai Yi-Shan , Chen Yung-Chih , Chao Hsiao-Han , Lin Hsin-Shih , Chiang Yi-Pin , Chen Hou-Yu 
Published: July 2021

Abstract
Background
One-handed backhand (OB) and two-handed backhand (TB) styles are commonly used in tennis, but only TB generates loadings on the non-dominant arm and a greater extension torque on the rear leg, leading to a greater axial torque involving rotation of the hip and trunk. The current study investigated whether those effects can further affect bone area (BA), bone mineral content (BMC) and density (BMD) in postmenopausal recreational tennis players.

Methods
BA, BMC and BMD of the lumbar spine, hip and distal radius were assessed using dual-energy X-ray absorptiometry in TB, OB, and swimmers’ group as a control (SG) (all participants self-reported for at least 5 years of exercise history, n = 14 per group). Muscular strength was assessed with a hand dynamometer. Among these three groups, the BA, BMC and BMD of distal radius and muscle strength were assessed using one-way ANOVA, and those of the lumbar region and the hip joint were tested by one-way ANCOVA.

Results
TB showed higher BMC and BMD for both lumbar spine and femoral neck than SG (all, p < 0.05). Both OB and TB showed greater BMD inter-trochanter than SG (both, p < 0.05). OB demonstrated greater inter-arm differences in the distal radius, which involved 1/3 distal for BMC and mid-distal radius for BMD compared to the TB and SG (all, p < 0.05). In addition, greater inter-arm asymmetry of grip strength was found in OB compared to TB and SG (both, p < 0.05).

Conclusion
For postmenopausal women, performing two-handed backhand strokes, leads to higher BMC and BMD in the non-dominant arm, the lumbar region, and hips, indicating potential benefit to maintain bone health and strength. Whether this result leads to reducing the risk of osteoporosis needs to be investigated in further research.
Measurement of empathy among health professionals during Syrian crisis using the Syrian empathy scale
Authors: Dashash Mayssoon , Boubou Mounzer 
Published: July 2021

Abstract
Background
Health professionals should have certain degree of empathy to eliminate the pain and suffering of their patients. There is a need to design a scale, which can assess empathy among health professionals and is relevant to community and culture. Therefore, this study was undertaken to measure the empathy among Syrian health professionals and students of health professions using a newly designed Syrian Empathy Scale that is relevant to community during Syrian crisis.

Methods
A cross-sectional observational study was undertaken. A total of 214 participants (118 males and 96 females) responded to the Syrian Empathy Scale SES from Medical (n = 62), Dental (n = 152). They were 59 undergraduates, 116 postgraduates and 39 general practitioners. The SES was designed as a tool that includes 20 items in a 7-point Likert-type scale with overall score ranges from 20 to 140. Group comparisons of the empathy scores were conducted using t-test and analysis of variance (ANOVA). A factor analysis was performed. Bartlett’s test of the sphericity and the KMO measure of sampling adequacy were also determined. Cronbach’s alpha was calculated.

Results
A significant difference was found between males and females in the SES mean score. The ANOVA analysis showed that the SES empathy scores of dentists were higher than the SES empathy scores in medical doctors with no significant difference. The SES empathy score of undergraduates was significantly higher than postgraduates and practitioners. Findings of KMO indicated sampling adequacy (KMO = 0.824 > 0.7) and the value of Bartlett’s test of the sphericity (1255.65, df = 190, P-value< 0.001) proved that the factor analysis is meaningful and acceptable. The results of varimax rotation proved that five main factors were retained.

Conclusion
Findings of this study support the reliability of the newly designed Syrian Empathy Scale for measuring empathy in the field of health care. The SES can be suggested for assessing empathy in different health educational programs. However, future works are still essential to support the validity of the scale as well as to ascertain the role of empathy in improving health care.
Health care ethics programs in U.S. Hospitals: results from a National Survey
Authors: Danis Marion , Fox Ellen , Tarzian Anita , Duke Christopher C. 
Published: July 2021

Abstract
Background
As hospitals have grown more complex, the ethical concerns they confront have grown correspondingly complicated. Many hospitals have consequently developed health care ethics programs (HCEPs) that include far more than ethics consultation services alone. Yet systematic research on these programs is lacking.

Methods
Based on a national, cross-sectional survey of a stratified sample of 600 US hospitals, we report on the prevalence, scope, activities, staffing, workload, financial compensation, and greatest challenges facing HCEPs.

Results
Among 372 hospitals whose informants responded to an online survey, 97% of hospitals have HCEPs. Their scope includes clinical ethics functions in virtually all hospitals, but includes other functions in far fewer hospitals: ethical leadership (35.7%), regulatory compliance (29.0%), business ethics (26.2%), and research ethics (12.6%). HCEPs are responsible for providing ongoing ethics education to various target audiences including all staff (77.0%), nurses (59.9%), staff physicians (49.0%), hospital leadership (44.2%), medical residents (20.3%) and the community/general public (18.4%). HCEPs staff are most commonly involved in policy work through review of existing policies but are less often involved in development of new policies. HCEPs have an ethics representative in executive leadership in 80.5% of hospitals, have representation on other hospital committees in 40.7%, are actively engaged in community outreach in 22.6%, and lead large-scale ethics quality improvement initiatives in 17.7%. In general, major teaching hospitals and urban hospitals have the most highly integrated ethics programs with the broadest scope and greatest number of activities. Larger hospitals, academically affiliated hospitals, and urban hospitals have significantly more individuals performing HCEP work and significantly more individuals receiving financial compensation specifically for that work. Overall, the most common greatest challenge facing HCEPs is resource shortages, whereas underutilization is the most common greatest challenge for hospitals with fewer than 100 beds. Respondents’ strategies for managing challenges include staff training and additional funds.

Conclusions
While this study must be cautiously interpreted due to its limitations, the findings may be useful for understanding the characteristics of HCEPs in US hospitals and the factors associated with these characteristics. This information may contribute to exploring ways to strengthen HCEPs.