bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined CDK4/6 and ERK1/2 Inhibition Enhances Antitumor Activity in NF1-Associated Plexiform Neurofibroma
Authors: Flint Alyssa C. , Mitchell Dana K. , Angus Steven P. , Smith Abbi E. , Bessler Waylan , Jiang Li , Mang Henry , Li Xiaohong , Lu Qingbo , Rodriguez Brooke , Sandusky George E. , Masters Andi R. , Zhang Chi , Dang Pengtao , Koenig Jenna , Johnson Gary L. , Shen Weihua , Liu Jiangang , Aggarwal Amit , Donoho Gregory P. , Willard Melinda D. , Bhagwat Shripad V. , Clapp D. Wade , Rhodes Steven D. 
Published: July 2023

Abstract

Purpose:
Plexiform neurofibromas (PNF) are peripheral nerve sheath tumors that cause significant morbidity in persons with neurofibromatosis type 1 (NF1), yet treatment options remain limited. To identify novel therapeutic targets for PNF, we applied an integrated multi-omic approach to quantitatively profile kinome enrichment in a mouse model that has predicted therapeutic responses in clinical trials for NF1-associated PNF with high fidelity.

Experimental Design:
Utilizing RNA sequencing combined with chemical proteomic profiling of the functionally enriched kinome using multiplexed inhibitor beads coupled with mass spectrometry, we identified molecular signatures predictive of response to CDK4/6 and RAS/MAPK pathway inhibition in PNF. Informed by these results, we evaluated the efficacy of the CDK4/6 inhibitor, abemaciclib, and the ERK1/2 inhibitor, LY3214996, alone and in combination in reducing PNF tumor burden in Nf1flox/flox;PostnCre mice.

Results:
Converging signatures of CDK4/6 and RAS/MAPK pathway activation were identified within the transcriptome and kinome that were conserved in both murine and human PNF. We observed robust additivity of the CDK4/6 inhibitor, abemaciclib, in combination with the ERK1/2 inhibitor, LY3214996, in murine and human NF1(Nf1) mutant Schwann cells. Consistent with these findings, the combination of abemaciclib (CDK4/6i) and LY3214996 (ERK1/2i) synergized to suppress molecular signatures of MAPK activation and exhibited enhanced antitumor activity in Nf1flox/flox;PostnCre mice in vivo.

Conclusions:
These findings provide rationale for the clinical translation of CDK4/6 inhibitors alone and in combination with therapies targeting the RAS/MAPK pathway for the treatment of PNF and other peripheral nerve sheath tumors in persons with NF1.
Disability Caused by Cleft Lip and Palate: A Systematic Review and Critical Valuation Appraisal
Authors: Blum Jessica D. , Benítez Diana Bohórquez , Caballero Felix Robles , Villavisanis Dillan F. , Cho Daniel Y. , Bartlett Scott P. , Taylor Jesse A. , Magee Leanne , Sierra Nicolas E. , Swanson Jordan W. 
Published: July 2023

Objective Measuring disability as a concept of impaired global function enables beneficiaries of treatment, the impact of treatment, and targets of health system investment to be rigorously assessed. Measures of disability are not well established for cleft lip and palate. This study aims to systematically review disability weight (DW) studies pertaining to orofacial clefts (OFCs) and identify methodological strengths and shortcomings of each approach. Design Systematic literature review of studies that met the following criteria: (1) peer-reviewed publication, (2) focus on disability valuation, (3) mention orofacial clefts, and (4) publication January 2001-December 2021. Setting None. Patients/Participants None. Interventions None. Main Outcome Measure(s) Disability weight method of valuation and the value itself. Results The final search strategy yielded 1,067 studies. Seven manuscripts were ultimately included for data extraction. The disability weights used in our studies, including those newly generated or taken from the Global Burden of Disease Studies (GBD), ranged widely for isolated cleft lip (0.0–0.100) and cleft palate with or without cleft lip (0.0−0.269). The GBD studies limited their consideration of cleft sequelae informing disability weights to impact on appearance and speech-related concerns, while other studies accounted for comorbidities such as pain and social stigma. Conclusions Current measures of cleft disability are sparse, inadequately reflect the comprehensive impact of an OFC on function and socialization, and are limited in detail or supporting evidence. Use of a comprehensive health state description in evaluating disability weights offers a realistic means of accurately representing the diverse sequelae of an OFC.
Comparing ART outcomes in women with endometriosis after GnRH agonist versus GnRH antagonist ovarian stimulation: a systematic review
Authors: Kuan Kevin K.W. , Omoseni Sean , Tello Javier A. 
Published: July 2023

Background: Endometriosis is an oestrogen-dependent disease that can cause subfertility in women who may require assisted reproductive technology (ART) to achieve their pregnancy goals. Objectives: The aim of this study was to compare ART outcomes in women with endometriosis following the long GnRH-agonist controlled ovarian stimulation (COS) protocol with those taking the GnRH-antagonist COS protocol. Data Sources and Methods: MEDLINE, Embase and Web of Science were systematically searched in June 2022. Randomized controlled trials (RCTs) and observational studies comparing the long GnRH-agonist COS protocol and the GnRH-antagonist COS protocol in women with all stages/subtypes of endometriosis were included. Data were synthesized into comprehensive tables for systematic review. The Scottish Intercollegiate Guidelines Network (SIGN) checklists were used for the risk of bias assessment of non-randomized studies and randomized studies, and all the included studies were deemed to have acceptable quality. Main Results: Eight studies (one RCT and seven observational) with 2695 patients (2761 cycles) were included. Most studies generally reported non-significant differences in clinical pregnancy or live birth rates regardless of the COS protocol used. However, the GnRH-agonist protocol may yield a higher total number of oocytes retrieved, especially mature oocytes. Conversely, the GnRH-antagonist protocol required a shorter COS duration and lower gonadotrophin dose. Adverse outcomes, such as rates of cycle cancellation and miscarriage, were similar between both COS protocols. Conclusion: Both the long GnRH-agonist and GnRH-antagonist COS protocols generally yield similar pregnancy outcomes. However, the long GnRH-agonist protocol may be associated with a higher cumulative pregnancy rate due to the higher number of retrieved oocytes available for cryopreservation. The underlying mechanisms of the two COS protocols on the female reproductive tract remain unclear. Clinicians should consider treatment costs, stage/subtype of endometriosis and pregnancy goals of their patients when selecting a GnRH analogue for COS. A well-powered RCT is needed to minimize the risk of bias and compare the risk for ovarian hyperstimulation syndrome. Registration: This review was prospectively registered at PROSPERO under Registration No. CRD42022327604.
Effect of COVID-19 Frontline Nurses’ Profession Perception on Their Intention to Stay: The Mediating Role of Job Satisfaction
Authors: Im Ahram , Koh Chin Kang 
Published: July 2023

Introduction Understanding the factors affecting the intention of frontline nurses during the coronavirus disease (COVID-19) pandemic to stay in the nursing profession is essential for developing strategies to overcome the challenges associated with the pandemic. Objectives This study aimed to examine the mediating effect of nurses’ job satisfaction on the relationship between their sense of calling, job-esteem, and the intention to stay in their profession. Methods The study used a previously collected dataset, sourced from a dedicated COVID-19 hospital in Seoul City, South Korea. Original data were collected from June to July 2021. The study sample consisted of 134 nurses who provided direct care to patients. The intention to stay was measured with the following question: “Are you willing to work during this COVID-19 pandemic?”. The Job Satisfaction Scale from the Korean Labor and Income Panel Study, Korean version of a Multidimensional Calling Measure, and Job-Esteem Scale for Hospital Nurses were utilized. Associations between the study variables were estimated using bivariate correlation analyses and bootstrapping mediation analyses. Results In the bivariate correlation analysis, nurses’ sense of calling ( r = .36, p < .001), job-esteem ( r = .32, p < .001), and job satisfaction ( r = .39, p < .001) were significantly associated with the intention to stay. In the mediation analysis, job satisfaction partially mediated the relationship between the sense of calling and the intention to stay (total effect; B = 0.410, p < .001) and fully mediated the relationship between job-esteem and the intention to stay (total effect; B = 0.549, p < .001). Conclusion Enhancing nurses’ job satisfaction is crucial for fostering the retention of the nursing workforce amid the pandemic. Consequently, it is imperative to closely examine the job satisfaction and work environment of frontline nurses to identify areas in need of improvement. Addressing the factors that impede nurses’ job satisfaction is essential to unlock the positive effects of a sense of calling and job-esteem.
Minimal change disease with papillary thyroid carcinoma: a report of two adult cases
Authors: Yin Juanjuan , Li Zexuan , Hao Zedong , Yu Zhuanzhuan , Yu Weimin , Yang Guang , Ren Xiaojun 
Published: July 2023

Abstract
Background
Minimal change disease (MCD), a pathological type of nephrotic syndrome (NS), can occur in patients with tumors. We report two adult cases of MCD associated with papillary thyroid carcinoma (PTC), known to be extremely rare in adults.

Case presentation
A 35-year-old female patient was simultaneously diagnosed with MCD and PTC. The MCD was effectively treated with thyroidectomy and prednisone.In addition, a 50-year-old male patient, who had been diagnosed with PTC three years prior, had MCD confirmed by renal biopsy. The patient achieved complete remission following treatment with tacrolimus and rituximab.

Conclusions
The present case report describes and discusses the diagnostic and treatment processes employed in these two patients. Clinicians need to be aware of the renal effects of treating patients with solid tumors.
BMI category-specific waist circumference thresholds based on cardiovascular disease outcomes and all-cause mortality: Tehran lipid and glucose study (TLGS)
Authors: Seyedhoseinpour Amirhosein , Barzin Maryam , Mahdavi Maryam , Valizadeh Majid , Azizi Fereidoun , Ghareh Sahar , Hosseinpanah Farhad 
Published: July 2023

Abstract
Background
Waist circumference (WC), a representative of abdominal visceral fat, is strongly associated with cardiovascular disease (CVD) and its outcomes. We aimed to define body mass index (BMI)-specific WC thresholds as predictors of CVD and all-cause mortality.

Methods
In this prospective cohort study in the context of the Tehran Lipid and Glucose Study (TLGS), a total of 3344 men and 4068 women were followed up for 18 years. Based on BMI, the participants were categorized into three groups: BMI < 25, 25 < BMI < 30, and BMI > 30. In each BMI category, sex-specific WC thresholds were estimated by the maximum value of Youden’s index to predict based on incident CVD events and all-cause mortality prediction.

Results
Overall 667 and 463 CVD events (the incidence rate of 3.1 to 4.5 in men and 1.1 to 2.6 in women per 1,000 person-years within BMI categories) and 438 and 302 mortalities (the incidence rate of 2.1 to 2.7 in men and 1.2 to 1.4 in women per 1,000 person-years within BMI categories) were recorded in men and women, respectively. WC thresholds in the BMI categories of < 25, 25–30, and BMI > 30 kg/m2 with regard to CVD events were 82, 95, and 103 cm in men and 82, 89, and 100 cm in women, and regarding all-cause mortality, the respective values were 88, 95, and 103 cm in men and 83, 90, and 99 cm among women.

Conclusion
BMI-specific WC thresholds observed here can help to better identify individuals at high risk of developing CVDs.
Medial augmentation plating of aseptic distal femoral nonunions
Authors: Lotzien Sebastian , Baron Darius , Rosteius Thomas , Cibura Charlotte , Ull Christopher , Schildhauer Thomas Armin , Geßmann Jan 
Published: July 2023

Abstract
Background
Distal femur nonunions are well-recognized contributors to persistent functional disability, with limited data regarding their treatment options. In the current study, we asked whether additional medial augmentation plating is a feasible treatment option for patients with aseptic distal femoral nonunion and intact lateral implants.

Methods
We conducted a single-center, retrospective study including 20 patients treated for aseptic distal femoral nonunion between 2002 and 2017. The treatment procedure included a medial approach to the distal femur, debridement of the nonunion site, bone grafting and medial augmentation plating utilizing a large-fragment titanium plate. Outcome measures were bone-related and functional results, measured by the Hospital for Special Surgery Knee Rating Scale (HSS) and the German Short Musculoskeletal Function Assessment questionnaire (SMFA-D).

Results
Eighteen of 20 nonunions showed osseous healing at 8.16 ± 5.23 (range: 3–21) months after augmentation plating. Regarding functional results, the mean HSS score was 74.17 ± 11.12 (range: 57–87). The mean SMFA-D functional index was 47.38 ± 16.78 (range 25.74–71.32) at the last follow-up. Index procedure-associated complications included two cases of persistent nonunion and one case of infection.

Conclusions
According to the assessed outcome measures, augmentation plating is a feasible treatment option, with a high proportion of patients achieving bony union and good functional outcomes and a few patients experiencing complications.
Can convertible metal-backed glenoid components replace cemented polyethylene glenoid components in anatomical total shoulder arthroplasty?
Authors: Kim Myung-Sun , Ahn Yeong-Seub , Lee Sun-Ho , Jeong Hyeon Jang , Kim Young Kyu , Oh Joo Han 
Published: July 2023

Abstract
Background
Anatomical total shoulder arthroplasty (aTSA) has been used to manage degenerative diseases such as primary osteoarthritis. An increase in the use of this procedure has led to several developments in humeral and glenoid components to improve patient outcomes. This study aimed to compare clinical and radiological outcomes of the newly-introduced convertible metal-backed glenoid components with cemented polyethylene glenoid components in aTSA, and to determine whether the new component would be comparable to a conventional one for reducing the burden of future revision or conversion surgeries.

Methods
Medical records of fifty patients who underwent aTSA with at least two years of follow-up were retrospectively reviewed. Eighteen patients received convertible metal-backed glenoid components with vitamin E1-coated liner (MB group), while thirty-two patients received conventional cemented polyethylene glenoid components (PE group). Pre- and postoperative clinical and radiological outcomes (acromion-greater tuberosity angle [AGA] and humeral lateral offset [LO]) at final follow-up were assessed. Radiolucent lines (RLLs) and loosening around the humeral and glenoid components were also evaluated.

Results
Clinical outcomes improved after surgery in both groups (all p < 0.001). The arc of rotation measured by AGA improved postoperatively in both groups (all p < 0.001), and AGA and LO were not different according to the type of glenoid components (all p > 0.05). Overall complication rates including RLLs of PE and MB groups were 43.8% (14/32) and 16.7% (3/18), respectively (p = 0.031). Although the PE group had more RLLs than did the MB group (p < 0.05), related symptoms and/or glenoid implant loosening were not observed in both groups. Subscapularis failure occurred in two patients in the PE group and in one in the MB group.

Conclusion
The convertible metal-backed glenoid implant with vitamin E1-coated liner may be a good alternative for considering the potential for an easier conversion to reverse total shoulder arthroplasty.
Dietary acid load and its interaction with CETP TaqB1 polymorphisms on lipid profile among patients with Type 2 diabetes mellitus
Authors: Abaj Faezeh , Esmaeily Zahra , Naeini Zeinab , Alvandi Ehsan , Rafiee Masoumeh , Koohdani Fariba 
Published: July 2023

Abstract
Objective
Gene-diet interaction plays a key role in the inter-individual differences in lipid abnormalities as a major risk factor for cardiovascular diseases (CVDs). Thus, we explored the interaction between CETP TaqB1 polymorphism with dietary acid load (DAL) on lipid profile among type 2 diabetes mellitus (T2DM).

Method
This cross-sectional study conducted on 220 Iranian patients with T2DM. Dietary acid load (PRAL and NEAP) was calculated via a validated food-frequency questionnaire (FFQ). The polymerase chain reaction (PCR) used for genotyping Taq1B polymorphism. Biochemical markers were measured by standard protocol. The interaction between CETP Taq1B polymorphism and DAL (PRAL and NEAP) on lipid profile was performed by a generalized linear regression model (GLM).

Results
The overall prevalence of rs708272 genotypes was 8.6%, 72.7% and 18.6% for B1B1, B1B2 and B2B2 genotype respectively. This study showed that people with the B1B1 genotype had greater LDL, TC, LDL/HDL, and TG when they consumed diets that scored higher on the NEAP and PRAL indexes than those with the B1B2 and B2B2 genotypes. Besides, carriers of the B1B1 allele who were in the highest tertile of NEAP, had lower HDL (P Interaction < 0.05).

Conclusions
In summary, the lipid profile might be improved in B1B1 homozygotes by less adherence to DAL indexes, however, the findings should be validated in high-quality interventional studies.
Proteomic profiling of longitudinal changes in kidney function among middle-aged and older men and women: the KORA S4/F4/FF4 study
Authors: Lin Jie-sheng , Nano Jana , Petrera Agnese , Hauck Stefanie M. , Zeller Tanja , Koenig Wolfgang , Müller Christian L. , Peters Annette , Thorand Barbara 
Published: July 2023

AbstractBackgroundDue to the asymptomatic nature of the early stages, chronic kidney disease (CKD) is usually diagnosed at late stages and lacks targeted therapy, highlighting the need for new biomarkers to better understand its pathophysiology and to be used for early diagnosis and therapeutic targets. Given the close relationship between CKD and cardiovascular disease (CVD), we investigated the associations of 233 CVD- and inflammation-related plasma proteins with kidney function decline and aimed to assess whether the observed associations are causal.MethodsWe included 1140 participants, aged 55–74 years at baseline, from the Cooperative Health Research in the Region of Augsburg (KORA) cohort study, with a median follow-up time of 13.4 years and 2 follow-up visits. We measured 233 plasma proteins using a proximity extension assay at baseline. In the discovery analysis, linear regression models were used to estimate the associations of 233 proteins with the annual rate of change in creatinine-based estimated glomerular filtration rate (eGFRcr). We further investigated the association of eGFRcr-associated proteins with the annual rate of change in cystatin C-based eGFR (eGFRcys) and eGFRcr-based incident CKD. Two-sample Mendelian randomization was used to infer causality.ResultsIn the fully adjusted model, 66 out of 233 proteins were inversely associated with the annual rate of change in eGFRcr, indicating that higher baseline protein levels were associated with faster eGFRcr decline. Among these 66 proteins, 21 proteins were associated with both the annual rate of change in eGFRcys and incident CKD. Mendelian randomization analyses on these 21 proteins suggest a potential causal association of higher tumor necrosis factor receptor superfamily member 11A (TNFRSF11A) level with eGFR decline.ConclusionsWe reported 21 proteins associated with kidney function decline and incident CKD and provided preliminary evidence suggesting a potential causal association between TNFRSF11A and kidney function decline. Further Mendelian randomization studies are needed to establish a conclusive causal association.
Initial insights into the impact and implementation of Creating Active Schools in Bradford, UK
Authors: Morris Jade L. , Chalkley Anna E. , Helme Zoe E. , Timms Oliver , Young Emma , McLoughlin Gabriella M. , Bartholomew John B. , Daly-Smith Andy 
Published: July 2023

Abstract
Background
Few whole-school physical activity programmes integrate implementation science frameworks within the design, delivery, and evaluation. As a result, knowledge of the key factors that support implementation at scale is lacking. The Creating Active Schools (CAS) programme was co-designed and is underpinned by the Capability, Opportunity, Motivation and Behaviour (COM-B) model and the Consolidated Framework for Implementation Research (CFIR). The study aims to understand the initial impact and implementation of CAS in Bradford over 9 months using McKay’s et al.’s (2019) implementation evaluation roadmap.

Methods
Focus groups and interviews were conducted with school staff (n = 30, schools = 25), CAS Champions (n = 9), and the CAS strategic lead (n = 1). Qualitative data were analysed both inductively and deductively. The deductive analysis involved coding data into a priori themes based on McKay et al’s implementation evaluation roadmap, using a codebook approach to thematic analysis. The inductive analysis included producing initial codes and reviewing themes before finalising.

Results
Identified themes aligned into three categories: (i) key ingredients for successful adoption and implementation of CAS, (ii) CAS implementation: challenges and solutions, and (iv) the perceived effectiveness of CAS at the school level. This included the willingness of schools to adopt and implement whole-school approaches when they are perceived as high quality and aligned with current school values. The programme implementation processes were seen as supportive; schools identified and valued the step-change approach to implementing CAS long-term. Formal and informal communities of practice provided “safe spaces” for cross-school support. Conversely, challenges persisted with gaining broader reach within schools, school staff’s self-competence and shifting school culture around physical activity. This resulted in varied uptake between and within schools.

Conclusions
This study provides novel insights into the implementation of CAS, with outcomes aligning to the adoption, reach, and sustainability. Successful implementation of CAS was underpinned by determinants including acceptability, intervention complexity, school culture and school stakeholders’ perceived self-efficacy. The combination of McKay’s evaluation roadmap and CFIR establishes a rigorous approach for evaluating activity promotion programmes underpinned by behavioural and implementation science. Resultantly this study offers originality and progression in understanding the implementation and effectiveness of whole-school approaches to physical activity.