bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality of life with palbociclib plus fulvestrant versus placebo plus fulvestrant in postmenopausal women with endocrine-sensitive hormone receptor-positive and HER2-negative advanced breast cancer: patient-reported outcomes from the FLIPPER trial
Authors: Tibau Ariadna , Martínez M. Teresa , Ramos Manuel , De La Cruz-Merino Luis , Santaballa Ana , O’Connor Miriam , Martínez-Jañez Noelia , Moreno Fernando , Fernández Isaura , Virizuela Juan Antonio , Alarcón Jesús , de La Haba-Rodríguez Juan , Sánchez-Rovira Pedro , Albacar Cinta Rosa , Bueno Muiño Coralia , Kelly Catherine , Casas Maribel , Bezares Susana , Rosell Libertad , Albanell Joan 
Published: January 2023

Background: In the FLIPPER trial, palbociclib/fulvestrant significantly improved progression-free survival (PFS) compared with placebo/fulvestrant in postmenopausal women with HR+/HER2− advanced breast cancer (ABC). Objective: We assessed health-related quality of life (QoL) using patient-reported outcomes (PROs). Design and methods: In this phase II double-blinded study, PROs were assessed at baseline after every three cycles and at the end of the treatment using the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BR23. Time to deterioration (TTD) in global health status (GHS)/QoL was defined as a decrease of ⩾10 points. Changes from baseline (CFB) and TTD were analysed using linear mixed-effect and Cox regression models, respectively. Results: Of the 189 randomised (1:1) patients, 178 (94%) completed ⩾1 post-baseline assessment; 50% received ⩾22 cycles of study treatment, with a questionnaire compliance >90%. Mean baseline scores were comparable between arms. GHS/QoL scores were maintained throughout the palbociclib/fulvestrant treatment. CFB showed significant differences for GHS/QoL, appetite loss, constipation and systemic therapy side effect scores favouring placebo/fulvestrant. TTD in GHS/QoL was delayed in placebo/fulvestrant versus palbociclib/fulvestrant [30.3 versus 11.1 months; adjusted hazard ratio (aHR): 1.57, 95% CI: 1.03–2.39, p = 0.036]; this difference was not significant in patients with progressive disease (aHR: 1.2, 95% CI: 0.6–2.2, p = 0.658). No statistically significant differences in TTD were found for the other QLQ-C30 and QLQ-BR23 scales. Conclusions: Although TTD in GHS/QoL was prolonged with placebo/fulvestrant, no differences were observed on other functional or symptom scales. This finding and the improvement in PFS support the combination of palbociclib/fulvestrant as a beneficial therapeutic option for HR+/HER2− ABC. Trial registration number: Sponsor Study Code: GEICAM/2014-12 EudraCT Number: 2015-002437-21 ClinTrials.gov reference: NCT02690480
The Relative Citation Ratio: Evaluating a New Measure of Scientific Influence Among Academic Sports Medicine Surgeons
Authors: Smith Tiffany A. , Sudah Suleiman Y. , Manzi Joseph E. , Michel Christopher R. , Kerrigan Daniel J. , Dijanic Christopher N. , Constantinescu David S. , Menendez Mariano E. , Plyler Ryan 
Published: January 2023

Background: Objective measures of research influence are being increasingly utilized to evaluate and compare academic faculty. However, traditional bibliometrics, such as the Hirsch index and article citation count, are biased by time-dependent factors and are limited by a lack of field normalization. The relative citation ratio (RCR) is a new field- and time-normalized article-level metric developed by the National Institutes of Health (NIH). Purpose/Hypothesis: The purpose of this study was to evaluate the RCR among fellowship-trained academic sports medicine surgeons and to analyze physician factors associated with RCR values. We hypothesized that the mean RCR score for fellowship-trained academic sports medicine surgery faculty will fall above the NIH standard. Study Design: Cross-sectional study. Methods: A retrospective data analysis was performed using the iCite database for all fellowship-trained sports medicine surgery faculty associated with Accreditation Council for Graduate Medical Education–accredited orthopaedic surgery residency programs in December 2021. In eligible faculty, the mean RCR, weighted RCR, and total publication count were compared by sex, career duration, academic rank, and presence of additional degrees. A mean RCR value of 1.0 is the NIH-funded field-normalized standard. The data herein are presented as the median and interquartile range, in addition to the mean and standard deviation, to account for outliers of the mean and weighted RCR scores. Results: A total of 624 fellowship-trained sports medicine surgery faculty members from 160 orthopaedic surgery residency programs were included in the analysis. Overall, faculty produced impactful research, with a median RCR of 1.6 (interquartile range, 1.0-2.2) and a median weighted RCR of 19.3 (interquartile range, 5.1-69.3). Advanced academic rank and career longevity were associated with increased weighted RCR and total publication count. All subgroups analyzed had an RCR value >1.0. Conclusion: Study findings indicate that fellowship-trained academic sports medicine surgery faculty are highly productive and produce impactful research, as evidenced by the high median RCR value relative to the benchmark NIH RCR value of 1.0.
Safety evaluation of oubli fruit sweet protein (brazzein) derived from Komagataella phaffii, intended for use as a sweetener in food and beverages
Authors: Lynch Barry , Wang Tina , Vo Trung , Tafazoli Shahrzad , Ryder Jason 
Published: January 2023

Naturally sweet proteins have no glycemic effect and offer a fundamentally new approach to sweetness and health for individuals seeking to reduce their added sugar intake. However, unlike many commercial sweeteners, little research has been performed on the potential safety implications of adding these uniquely sweet proteins to food and beverages. In this study, a naturally sweet protein found in the West African Oubli plant ( Pentadiplandra brazzeana), referred to as Oubli fruit sweet protein or brazzein, was expressed in Komagataella phaffii (formerly Pichia pastoris) and produced via precision fermentation, and a safety and risk assessment was undertaken for its use as a sweetener in food and beverages. Potential consumption levels of brazzein were estimated to be 3 mg/kg body weight/day based on the National Health and Nutrition Examination Survey. The safety of brazzein derived from K. phaffii was evaluated through in silico allergenicity, in vitro genotoxicity (reverse mutation and mammalian micronucleus assays), and a 90-day dietary oral toxicity study in rats. There was no indication of allergenicity in the in silico analyses. Brazzein was non-genotoxic in the in vitro assays and showed no adverse effects in the 90-day oral toxicity study up to the highest dose tested, where the no-observed-adverse-effect level (NOAEL) was 978 and 985 mg/kg body weight/day in males and females, respectively. The totality of evidence in the in silico allergenicity, in vitro genotoxicity, and 90-day dietary toxicity studies demonstrates that brazzein derived from K. phaffii is considered safe for use as a sweetener in food and beverages.
A critical role of RUNX1 in governing megakaryocyte-primed hematopoietic stem cell differentiation
Authors: Wang Chen , Tu Zhaowei , Cai Xiongwei , Wang Weinan , Davis Ashely K. , Nattamai Kalpana , Paranjpe Aditi , Dexheimer Philip , Wu Jianqiang , Huang Frank Lei , Geiger Hartmut , Huang Gang , Zheng Yi 
Published: January 2023

Abstract
As a transcription factor in the RUNT domain core-binding factor family, RUNX1 is crucial in multiple stages of hematopoiesis, and its mutation can cause familial platelet disorder with a predisposition to acute myeloid leukemia. Previous work has established that RUNX1 is involved in the maturation of megakaryocytes (MKs) and the production of platelets. Recent studies have shown that there exists a subpopulation of hematopoietic stem cells (HSCs) with relatively high expression of von Willebrand factor and CD41 at the apex of the HSC hierarchy, termed MK-HSCs, which can give rise to MKs without going through the traditional differentiation trajectory from HSC via MPP (multipotent progenitors) and MEP (megakaryocyte–erythroid progenitor). Here, by using Runx1F/FMx1-Cre mouse model, we discovered that the MK-HSC to MK direct differentiation can occur within 1 cell division, and RUNX1 is an important regulator in the process. Runx1 knockout results in a drastic decrease in platelet counts and a severe defect in the differentiation from MK-HSCs to MKs. Single cell RNA sequencing (RNAseq) analysis shows that MK-HSCs have a distinct gene expression signature compared with non-MK–HSCs, and Runx1 deletion alters the platelet and MK-related gene expression in MK-HSCs. Furthermore, bulk RNAseq and Cut&Run analyses show that RUNX1 binds to multiple essential MK or platelet developmental genes, such as Spi1, Selp, and Itga2b and regulates their expressions in MK-HSCs. Thus, by modulating the expression of MK-related genes, RUNX1 governs the direct differentiation from MK-HSCs to MKs and platelets.
Spatial accuracy of computed tomography perfusion to estimate the follow-up infarct on diffusion-weighted imaging after successful mechanical thrombectomy
Authors: Xu Xiao-Quan , Ma Gao , Shen Guang-Chen , Lu Shan-Shan , Shi Hai-Bin , Zhang Ya-Xi , Zhang Yu , Wu Fei-Yun , Liu Sheng 
Published: January 2023

Abstract
Background
Volumetric accuracy of using computed tomography perfusion (CTP) to estimate the post-treatment infarct in stroke patients with successful recanalization after mechanical thrombectomy (MT) has been studied a lot, however the spatial accuracy and its influence factors has not been fully investigated.

Methods
This retrospective study reviewed the data from consecutive anterior large vessel occlusion (LVO) patients who had baseline CTP, successful recanalization after MT, and post-treatment diffusion-weighed imaging (DWI). Ischemic core on baseline CTP was estimated using relative cerebral blood flood (CBF) of < 30%. The infarct area was outlined manually on post-treatment DWI, and registered to CTP. Spatial agreement was assessed using the Dice similarity coefficient (DSC) and average Hausdorff distance. According to the median DSC, the study population was dichotomized into high and low Dice groups. Univariable and multivariable regression analyses were used to determine the factors independently associated with the spatial agreement.

Results
In 72 included patients, the median DSC was 0.26, and the median average Hausdorff distance was 1.77 mm. High Dice group showed significantly higher median ischemic core volume on baseline CTP (33.90 mL vs 3.40 mL, P < 0.001), lower proportion of moderate or severe leukoaraiosis [27.78% vs 52.78%, P = 0.031], and higher median infarct volume on follow-up DWI (51.17 mL vs 9.42 mL, P < 0.001) than low Dice group. Ischemic core volume on baseline CTP was found to be independently associated with the spatial agreement (OR, 1.092; P < 0.001).

Conclusions
CTP could help to spatially locate the post-treatment infarct in anterior LVO patients who achieving successful recanalization after MT. Ischemic core volume on baseline CTP was independently associated with the spatial agreement.
Validation of the Grobman model for successful vaginal birth after cesarean section in Jordanian women
Authors: Rawashdeh Hasan , Aljalodi Haneen , shamleh Rafeef Abu , Alshorman Sumyah , AboShindi Heba , Awawdeh Shatha 
Published: January 2023

Abstract
Background
To validate both models of Grobman nomogram (The antenatal and the intrapartum model) for predicting successful intended Vaginal Birth After Caesarean delivery (VBAC) in a Jordanian population.

Methods
A retrospective study has identified all live, singleton, term, cephalic pregnancies with a previous lower segment cesarean section who opted for a Trial Of Labour After Caesarean Section (TOLAC) between January 2014 to December 2020. Five variables were used for the antenatal model, while ten variables were used for the intrapartum model. Two sets of patients were created: one for the antenatal model and the other for the intrapartum model. The predicted probability for each woman was calculated and compared with the successful VBAC for each category. The predictive ability was assessed with a receiver operating characteristic, and the area under the curve (AUC) was determined.

Results
There were seven hundred and fourteen complete cases for the antenatal model and six hundred ninety-seven for the intrapartum model. Our population's overall number of VBAC is 83.89% for the antenatal group and 82.92% for the intrapartum group. The mean predicted probability for a successful intended VBAC using the antenatal and intrapartum models were 79.53 ± 13.47 and 78.64 ± 14.03, respectively. The antenatal and intrapartum predictive models ROC had an AUC of 65% (95% CI: 60%-71%) and 64% (95% CI: 58%-69%), respectively.

Conclusions
Both models are validated in the Jordanian population. Adapting the antenatal model as supporting evidence can lead to a higher rate of TOLAC.
Biomarker analysis for patients with pancreatic cancer treated with nanoliposomal irinotecan plus 5-fluorouracil/leucovorin
Authors: Kawakami Takeshi , Todaka Akiko , Oshima Kotoe , Fushiki Kunihiro , Hamauchi Satoshi , Tsushima Takahiro , Yokota Tomoya , Onozawa Yusuke , Yasui Hirofumi , Yamazaki Kentaro 
Published: January 2023

Abstract
Background
Nanoliposomal irinotecan plus fluorouracil/leucovorin (5-FU/LV) is a standard second-line therapy for patients with pancreatic cancer. Identification of biomarkers is important to determine appropriate treatment strategies. We investigated the clinical practice outcomes and biomarkers associated with the nanoliposomal irinotecan plus 5-FU/LV regimen.

Methods
We retrospectively reviewed the data of patients treated with nanoliposomal irinotecan plus 5-FU/LV as a second or subsequent treatment after gemcitabine-based therapy between June 2020 and March 2021 at Shizuoka Cancer Center.

Results
We analyzed 55 consecutive patients who met the selection criteria. At a median of 9.4 months, median progression-free survival (PFS) and median overall survival (OS) were 2.3 and 6.6 months, respectively. Multivariate analysis showed that Glasgow prognostic score (GPS) was significantly associated with PFS (hazard ratio [HR] 2.16; 95% confidence interval [CI] 1.09–4.30; P = 0.028) and OS (0 vs. 1 or 2: HR 2.46; 95% CI 1.15–5.25; P = 0.029). The OS was significantly longer in patients with CA19–9 response than in those without CA19–9 response (12.6 vs. 5.6 months; HR 0.24; 95% CI 0.08–0.75; P = 0.014).

Conclusions
Nanoliposomal irinotecan was efficacious and tolerable in clinical practice. GPS and CA19–9 response were good candidates as predictive biomarkers, whereas GPS was a good candidate prognostic biomarker for the nanoliposomal irinotecan plus 5-FU/LV regimen.
COVID-19 vaccine uptake and vaccine hesitancy in rural-to-urban migrant workers at the first round of COVID-19 vaccination in China
Authors: Hong Liuzhi , Jin Zhou , Xu Kewei , Shen Guanghui , Zou Yang , Li Ran , Xu Lu , Wang Dexuan , Chen Li , Wu Yili , Song Weihong 
Published: January 2023

Abstract
Background
Migration can be linked to the transmission of COVID-19. COVID-19 vaccine uptake and hesitancy among rural-to-urban migrant workers in China, the largest group of internal migrants in the world, has not been characterized.

Objective
To investigate COVID-19 vaccine uptake and identify vaccine hesitancy-associated factors among rural-to-urban migrant workers in the first round of COVID-19 vaccination in China.

Methods
A cross-sectional questionnaire-based survey was conducted, including 14,917 participants. Socio-demographics, COVID-19 vaccine uptake, vaccine hesitancy and its associated factors based on Vaccine Hesitancy Determinants Matrix (VHDM) were applied for the survey. Data were principally analyzed by logistic regression analysis.

Results
The COVID-19 vaccine uptake and vaccine hesitancy rates were 7.1% and 57.7%, respectively. Vaccine hesitancy was strongly associated with VHDM, including individual factors (female, higher annual income and fewer medical knowledge), group factors (less family support, friend support and public opinion support), COVID-19 epidemic factors (lower fatality, infection and emotional distress) and vaccine factors (less vaccine necessity, vaccine safety, vaccine efficacy, vaccine importance and vaccine reliability).

Conclusion
The VHDM model has the potential utility in efforts to reduce COVID-19 vaccine hesitancy. Greater efforts should be put into addressing positive predictors associated with vaccine hesitancy.
Positive effects of neuromuscular exercises on pain and active range of motion in idiopathic frozen shoulder: a randomized controlled trial
Authors: Wang Lu , Yu Ge , Zhang Ran , Wu Guangyan , He Lei , Chen Yaping 
Published: January 2023

Abstract
Background and objectives
Frozen shoulder (FS) is characterized by pain and significant loss of active and passive shoulder motion. Strengthening exercises are among the standard exercises used for FS. Neuromuscular exercise (NME) effectively improved pain and the range of motion in shoulder. However, no prior research has looked into the effects of NME compared to strengthening exercises in FS rehabilitation. The aim of the present study was to evaluate the effects of NME compared to strengthening exercises on pain and active range of motion (AROM) in individuals with idiopathic frozen shoulder.

Methods
Forty individuals with idiopathic frozen shoulder were randomly assigned to either the experimental group (NME with regular physical therapy, n = 20) or the control group (strengthening exercises with regular physical therapy, n = 20). In both groups, the interventions were performed once a day, 5 days a week for 8 weeks. Pain scores on the visual analogue scale (VAS) and AROM of the shoulder were assessed at baseline and after the 8-week treatment. The primary analysis was the group × time interaction.

Results
Two-by-two mixed analysis of variance (ANOVA) revealed a significant group × time interaction for VAS (F = 29.67; p < 0.01); AROM in flexion (F = 12.05; p < 0.01), internal rotation (F = 6.62; p < 0.05) and external rotation (F = 16.93; p < 0.01) in favor of the experimental group. The two-by-two mixed ANOVA revealed a significant main effect of time for VAS (F = 1648.47; p < 0.01); AROM in flexion (F = 591.70; p < 0.01), extension (F = 114.57; p < 0.01), abduction (F = 1602.04; p < 0.01), internal rotation (F = 664.14; p < 0.01) and external rotation (F = 1096.92; p < 0.01). No other significant differences were found.

Conclusions
NME is superior to strengthening exercises in terms of pain and AROM of shoulder flexion, internal rotation and external rotation in individuals with idiopathic FS. NME could be used to treat individuals with FS.

Trial registration
Trial registration number: ChiCTR2100054453. Registration date: 17/12/2021.
“A cross-sectional study of burnout among Australian general practice registrars”
Authors: Hoffman Rebekah , Mullan Judy , Bonney Andrew 
Published: January 2023

Abstract
Objective(s)
To identify if gender and parenting factors are associated with burnout in Australian general practice (GP) registrars.

Design
Cross sectional study. The main outcome measure was the Maslach Burnout Inventory, included as part of the GPRA (General Practice Registrars Australia) biannual online survey.
Participants: GP registrars, 2019 cohort, undertaking fellowship training in Australia.

Results
In 2019 a total of 366 GP registrars completed the online survey. Over 75% of registrars experienced moderate to high levels of burnout (emotional exhaustion scale). Several demographic factors were associated with an increased risk for reporting higher levels of burnout. Increasing age was associated with lower levels of personal accomplishment (P-value < 0.01), being female was associated with higher levels of emotional exhaustion (p-value < 0.001) and increasing numbers of children were associated with lower levels of burnout, independent of hours worked (p-value < 0.001).

Conclusion
This study suggests that being a parent is associated with a reduced risk of burnout, irrespective of hours worked. However, being female and increased age were associated with increased levels of burnout. With increasing numbers of females entering medical training, and the decreasing desirability of general practice training, this paper reviews the complexities around parenting during training and associations with burnout. There is a need to examine this interaction further to understand the causation for these findings, and to ensure appropriate policies, opportunities and workplace supports are developed to ensure GP training is optimised to attract and support the next generation.
Blocking RAGE expression after injury reduces inflammation in mouse model of acute lung injury
Authors: Johnson Lynne L. , Tekabe Yared , Zelonina Tina , Ma Xinran , Zhang Geping , Goldklang Monica , D’Armiento Jeanine 
Published: January 2023

Abstract
Background
Receptor for Advanced Glycated Endproducts (RAGE) plays a major role in the inflammatory response to infectious and toxin induced acute lung injury. We tested the hypothesis that a RAGE blocking antibody when administered after the onset of injury can reduce lung inflammation compared to control antibody.

Methods
Male and female C57BL/6 (WT) mice were used. Forty-six received lipopolysaccharide (LPS) and 26 PBS by nasal instillation on day one, repeated on day three. On day 2, 36 mice receiving LPS were divided into two groups of 18, one treated with 200 μg of non-immune isotype control IgG and the second group treated with 200 μg of anti-RAGE Ab, each dose divided between IV and IP. Ten of the 46 were not treated. On day 4, before euthanasia, mice were injected with fluorescein isothiocyanate (FITC) labelled albumen. BALF and serum samples were collected as well as lung tissue for immunohistochemistry (IHC). BALF was analyzed for cell (leukocyte) counts, for FITC BALF/serum ratios indicating pulmonary vascular leak, and for cytokines/chemokines using bead based multiplex assays. Quantitative IHC was performed for MPO and RAGE.

Results
Ten LPS mice showed minimal inflammation by all measures indicating poor delivery of LPS and were excluded from analysis leaving n = 11 in the LPS + IgG group and n = 12 in the LPS + anti-RAGE group. BALF cell counts were low in the PBS administered mice (4.9 ± 2.1 × 105/ml) and high in the LPS injured untreated mice (109 ± 34) and in the LPS + IgG mice (91 ± 54) while in comparison, LPS + anti-RAGE ab mice counts were significantly lower (51.3 ± 18 vs. LPS + IgG, P = 0.03). The BALF/serum FITC ratios were lower for the LPS + anti-RAGE mice than for the LPS + IgG mice indicating less capillary leakiness. Quantitative IHC RAGE staining was lower in the LPS + anti-RAGE ab mice than in the LPS + IgG treated mice (P = 0.02).

Conclusions
These results describe a four-day LPS protocol to sustain lung injury and allow for treatment and suggests that treatment aimed at blocking RAGE when given after onset of injury can reduce lung inflammation.
The efficacy of vitamin D supplementation for irritable bowel syndrome: narrow scope and GRADE miss-interpretation
Authors: Abuelazm Mohamed , Abdelazeem Basel 
Published: January 2023

AbstractWe read the article by Haung et al. that pooled the effects of vitamin D on irritable bowel syndrome symptoms and associated quality of life. However, the current review suffers from some methodological errors: inadequate search strategy; the grading of recommendations assessment, development, and evaluation (GRADE) miss-assessment; and miss-interpretation. Accordingly, addressing the emphasized limitations will lead to more robust findings and conclusions.