bluuebunny/crossref_metadata_2025_split huggingface dataset:
Commercial and public payer opioid analgesic prescribing policies: a case study
Authors: Arfken Cynthia L. , Tutag Lehr Victoria 
Published: January 2021

Abstract
Background
One strategy to address the high number of U.S. opioid-related deaths is to restrict high-risk or inappropriate opioid analgesic prescribing and dispensing. Federal and state laws and regulations have implemented restrictions but less is known about commercial and public payers’ policies aside from clinician anecdotal reports that these policies are increasing. To assess the number and types of policies with temporal trends, we examined commercial and public (Medicaid) payer policies in one state, Michigan, that has high opioid-related deaths and implemented opioid analgesic prescribing laws.

Methods
Policies for seven large commercial payers and the public payer for 2012–2018 were reviewed and categorized by actions. Joinpoint regression was used to summarize temporal trends on number of policies for all payers and subgroups.

Results
Across the 7 years, there were 529 action policies (75.57 (95% confidence intervals (CI) 35.93, 115.22) actions per year) with a range of 36 to 103 actions by payer. Limitations on number of days for initial prescriptions and prior authorizations were the most frequently implemented policy. The temporal trend showed a decline in new policies from 2012 to 2013 but a steady increase from 2014 to 2018 (average annual percent change or AAPC=29.6% (95% confidence intervals 13.2, 48.5%)). The public payer (n=47 policies) showed no increase in number of policies over time (AAPC=2.9% (95% CI -41.6, 61.6%).

Conclusions
The eight commercial and public payers implemented many new policies to restrict opioid analgesic prescribing with a steady increase in the number of such policies implemented from 2014 to 2018. This case study documented that at least in one state with high opioid-related deaths and multiple commercial payers, new and different policies were increasingly implemented creating barriers to patient care. The impact of these policies is understudied, complicating recommendation of best practices.
Surgical spacer placement for proton radiotherapy in locally advanced pancreatic body and tail cancers: initial clinical results
Authors: Lee Dongha , Komatsu Shohei , Terashima Kazuki , Toyama Hirochika , Matsuo Yoshiro , Takahashi Daiki , Suga Masaki , Nishimura Naoko , Tai Kentaro , Kido Masahiro , Demizu Yusuke , Tokumaru Sunao , Okimoto Tomoaki , Sasaki Ryohei , Fukumoto Takumi 
Published: January 2021

AbstractBackgroundParticle radiotherapy has increasingly gained acceptance for locally advanced pancreatic cancers owing to superior tumor conformity and dosimetry compared to conventional photon radiotherapy. However, the close proximity of the pancreas to the stomach and duodenum leads to radiation-induced gastrointestinal toxicities, which hinder the delivery of curative doses to the tumor. To overcome this problem, a surgical spacer was placed between the tumor and gastrointestinal tract, and subsequent proton radiotherapy was performed in this study.MethodsData from 9 patients who underwent surgical spacer placement and subsequent proton radiotherapy were analyzed. The safety and feasibility of the spacer placement surgery were evaluated; the impact of the spacer on dosimetry was also assessed using dose volume histogram (DVH) analyses, before and after surgical spacer placement.ResultsSurgical spacer placement and subsequent proton radiotherapy were successfully completed in all cases. Surgical spacer placement significantly improved the dose intensity covering 95%, mean, and minimum doses for the gross tumor volume, and the clinical and planning target volume based on the DVH, while respecting the dose constraints of the gastrointestinal tract. Based on the Common Terminology Criteria for Adverse Events, two patients (22.2%) developed gastrointestinal ulcer (Grade 2) at 1 and 35 months, and one patient (11.1%) developed gastric perforation (Grade 4) at 4 months after proton radiotherapy.ConclusionsSurgical spacer placement in the locally advanced pancreatic body and tail cancers is relatively safe and technically feasible. Comparing radiation plans, surgical spacer placement seems to improve the dose distribution in the locally advanced pancreatic body and tail cancers, which are close to the gastrointestinal tract.
Efficacy of mesenchymal stromal cells for the treatment of knee osteoarthritis: a meta-analysis of randomized controlled trials
Authors: Qu Huazheng , Sun Shui 
Published: January 2021

Abstract
Background
Mesenchymal stromal cells (MSCs) are used as an emerging new option for the treatment of knee osteoarthritis (OA). However, their efficacy remains controversial across studies with different doses of MSCs and cell processing methods. We conducted this meta-analysis to assess the efficacy of MSCs in the treatment of knee OA.

Methods
Randomized controlled trials (RCTs) published in PubMed, Embase, Web of Science, SinoMed (Chinese BioMedical Literature Service System, China), and CNKI (National Knowledge Infrastructure, China) databases were systematically reviewed. The pain level and function improvements were evaluated using visual analog scale (VAS), McMaster Universities Osteoarthritis Index (WOMAC), and International Knee Documentation Committee (IKDC). The pooled estimate was calculated with weighted mean difference (WMD) with 95% confidence intervals (95%CIs).

Results
Nine RCTs involving 476 patients were included in this meta-analysis. The pooled estimate showed that the treatment of MSCs significantly reduced VAS, WOMAC pain, WOMAC stiffness, and WOMAC function scores at a long-term follow-up (12 or 24 months). However, for the IKDC and WOMAC total scores, MSCs also showed significant improvement in these outcomes, although this was not statistically significant when compared to the control.

Conclusion
Based on the current studies, our results suggested that MSCs were a promising option for the treatment of patients with knee OA. However, considering the potential limitations, more well-performed, large-scale RCTs are needed to verify our findings.
The impact of different artificial disc heights during total cervical disc replacement: an in vitro biomechanical study
Authors: Wang Xiao-Fei , Meng Yang , Liu Hao , Wang Bei-Yu , Hong Ying 
Published: January 2021

Abstract
Background
The principles of choosing an appropriate implant height remain controversial in total cervical disc replacement (TDR). By performing an in vitro biomechanical study and exploring the biomechanical impact of implant height on facet joint and motion function, the study aimed to offer valid proposals regarding implant height selection during TDR.

Methods
A total of 6 fresh-frozen male cadaveric cervical spines (C2–C7) with 5 mm intervertebral disc height at C5/6 level were enrolled in the study. Specimens with the intact condition and with different height artificial discs were tested. Facet joint pressures and range of motion under each condition were recorded using a specialized machine.

Results
The artificial disc heights that were involved in this study were 5 mm, 6 mm, and 7 mm. The range of motion decreased along with the increment of implant height, while facet joint pressure showed an opposite trend. Specimens with a 5 mm implant height could provide a similar range of motion (11.8° vs. 12.2° in flexion-extension, 8.7° vs. 9.0° in rotation, 7.9° vs. 8.2° in lateral bending) and facet joint pressure (27.8 psi vs. 25.2 psi in flexion, 59.7 psi vs. 58.9 psi in extension, 24.0 psi vs. 22.7 psi in rotation, 32.0 psi vs. 28.8 psi in lateral bending) compared with intact specimens. Facet joint pressure of specimens with 6 mm implant height (≥ 1 mm in height) increased during flexion at the C5–6 segment (30.4 psi vs. 25.2 psi, P = 0.076). However, specimens with 7 mm implant height (≥ 2 mm in height) showed a significant reduction in motion (9.5° vs. 12.2° in flexion-extension, P < 0.001) and increment of facet joint pressure at C5–6 segment (44.6 psi vs. 25.2 psi in flexion, 90.3 psi vs. 58.9 psi in extension, P < 0.0001) and adjacent segments.

Conclusions
This study suggested that an appropriate artificial disc height can achieve near-normal biomechanical properties and is recommended. We should be very cautious when using artificial discs ≥ 1 mm in height compared to normal. However, implants ≥ 2 mm in height compared to normal significantly increased the facet joint pressure and decreased the range of motion; therefore, it should not be used in clinical practice.
Application of bilateral internal mammary artery with different configurations in coronary artery bypass grafting
Authors: Han Zengqiang , Zhang Guodong , Chen Shenglong , Liu Gang , Chen Yu 
Published: January 2021

Abstract
Background
A large number of studies have shown that BIMA grafting is superior to single internal mammary artery grafting in cardiac function protection and long-term survival after surgery. While, there is still no consensus on how is the best configuration to use BIMA. This study aims to compare intraoperative blood flow, early clinical results and early postoperative patency of different configurations of BIMA.

Methods
There were 74 patients who underwent CABGs with bilateral internal mammary artery with different configurations we included. According to the different target territories that RIMA grafted to, the patients were divided into bilateral group (group I) with 20 cases and left group (group II) with 54 cases. Intraoperative blood flow, early clinical results and early postoperative patency of different configurations of BIMA were compared.

Results
There was no difference in the early postoperative death and major complications between group I and Group II(P>0.05). Compared with the LIMA in group II, the LIMA in group I had a slightly higher DF value (76.7 ± 6.2 vs 73.1 ± 6.8, P = 0.040). Compared with the RIMA in group II, the RIMA in group I had a slightly higher MGF (51.7 ± 34.4 ml/min vs 31.4 ± 21.4 ml/min, P = 0.024). There was no difference in the other TTFM parameters of LIMA and RIMA between group I and Group II(P>0.05). Further subgroup analysis revealed that compared with free RIMA in group II, in situ RIMA had a higher DF value (71.4 ± 7.8 vs 61.8 ± 18.1,P = 0.025). The PI of LIMA in free RIMA subgroup was higher than the PI of LIMA in in-situ RIMA subgroup (3.0 ± 1.6 vs 2.1 ± 1.0,P = 0.018). The results of early postoperative CTA examination showed that all IMAs grafts were completely patent.

Conclusions
The use of BIMA for CABG is safe and efficacious, RIMA used in right coronary artery received more satisfactory graft flow. BIMA with no stenosis and occlusion in the early stage, therefore is the ideal and stable coronary bypass graft.
Rare and low frequency genomic variants impacting neuronal functions modify the Dup7q11.23 phenotype
Authors: Qaiser Farah , Yin Yue , Mervis Carolyn B. , Morris Colleen A. , Klein-Tasman Bonita P. , Tam Elaine , Osborne Lucy R. , Yuen Ryan K. C. 
Published: January 2021

Abstract
Background
7q11.23 duplication (Dup7) is one of the most frequent recurrent copy number variants (CNVs) in individuals with autism spectrum disorder (ASD), but based on gold-standard assessments, only 19% of Dup7 carriers have ASD, suggesting that additional genetic factors are necessary to manifest the ASD phenotype. To assess the contribution of additional genetic variants to the Dup7 phenotype, we conducted whole-genome sequencing analysis of 20 Dup7 carriers: nine with ASD (Dup7-ASD) and 11 without ASD (Dup7-non-ASD).

Results
We identified three rare variants of potential clinical relevance for ASD: a 1q21.1 microdeletion (Dup7-non-ASD) and two deletions which disrupted IMMP2L (one Dup7-ASD, one Dup7-non-ASD). There were no significant differences in gene-set or pathway variant burden between the Dup7-ASD and Dup7-non-ASD groups. However, overall intellectual ability negatively correlated with the number of rare loss-of-function variants present in nervous system development and membrane component pathways, and adaptive behaviour standard scores negatively correlated with the number of low-frequency likely-damaging missense variants found in genes expressed in the prenatal human brain. ASD severity positively correlated with the number of low frequency loss-of-function variants impacting genes expressed at low levels in the brain, and genes with a low level of intolerance.

Conclusions
Our study suggests that in the presence of the same pathogenic Dup7 variant, rare and low frequency genetic variants act additively to contribute to components of the overall Dup7 phenotype.
Fingolimod in children with Rett syndrome: the FINGORETT study
Authors: Naegelin Yvonne , Kuhle Jens , Schädelin Sabine , Datta Alexandre N. , Magon Stefano , Amann Michael , Barro Christian , Ramelli Gian Paolo , Heesom Kate , Barde Yves-Alain , Weber Peter , Kappos Ludwig 
Published: January 2021

Abstract
Background
Rett syndrome (RS) is a severe neurodevelopmental disorder for which there is no approved therapy.
This study aimed to assess safety and efficacy of oral fingolimod in children with RS using a pre-post and case–control design.

Methods
At the University of Basel Children’s Hospital, Basel, Switzerland, children with RS were included if they were older than 6 years and met the established diagnostic criteria of RS, including a positive MeCP2 mutation. Participants were observed 6 months before and after treatment and received 12 months of fingolimod treatment. Serum samples of 50 children without RS served as reference for brain-derived neurotrophic factor (BDNF) measurements. Primary outcome measures were safety and efficacy, the latter measured by change in levels of BDNF in serum/CSF (cerebrospinal fluid) and change in deep gray matter volumes measured by magnetic resonance imaging (MRI). Secondary outcome measure was efficacy measured by change in clinical scores [Vineland Adaptive Behaviour Scale (VABS), Rett Severity Scale (RSSS) and Hand Apraxia Scale (HAS)].

Results
Six children with RS (all girls, mean and SD age 11.3 ± 3.1 years) were included. Serum samples of 50 children without RS (25 females, mean and SD age 13.5 ± 3.9 years) served as reference for BDNF measurements. No serious adverse events occurred. Primary and secondary outcome measures were not met. CSF BDNF levels were associated with all clinical scores: RSSS (estimate − 0.04, mult.effect 0.96, CI [0.94; 0.98], p = 0.03), HAS (estimate − 0.09, mult.effect 0.91, CI [0.89; 0.94], p <  0.01) and VABS (communication: estimate 0.03, mult.effect 1.03, CI [1.02; 1.04], p < 0.01/daily living: estimate 0.03, mult.effect 1.03, CI [1.02; 1.04], p < 0.01/social skills: estimate 0.07, mult.effect 1.08, CI [1.05; 1.11], p < 0.01/motoric skills: estimate 0.04, mult.effect 1.04, CI [1.03; 1.06], p = 0.02).

Conclusions
In children with RS, treatment with fingolimod was safe. The study did not provide supportive evidence for an effect of fingolimod on clinical, laboratory, and imaging measures. CSF BDNF levels were associated with clinical scores, indicating a need to further evaluate its potential as a biomarker for RS. This finding should be further validated in independent patient groups.

Trial Registration
Clinical Trials.gov NCT02061137, registered on August 27th 2013, https://clinicaltrials.gov/ct2/show/study/NCT02061137.
Depressive symptoms and their determinants in patients who are on antiretroviral therapy in the case of a low-income country, Ethiopia: a systematic review and meta-analysis
Authors: Necho Mogesie , Belete Asmare , Tsehay Mekonnen 
Published: January 2021

Abstract
Background
The presence of depression in people living with HIV/AIDS could lead to non-adherence to antiretroviral medications. It also leads to further comorbid and opportunistic illness and then lowering the patient's quality of life. The objective of this study was therefore to determine the pooled prevalence of depression and its related factors in HIV patients.

Methods
Relevant articles in PubMed, Scopus, and EMBASE were investigated. The Meta-XL version 5.3 was used to extract data and STATA-11 Meta-prop packages with the Random effect model was used to quantify depression and its related factors. Sensitivity and subgroup analysis were performed to explore sources of heterogeneity. The Cochran’s Q-statistic and the Higgs I2 test were also done. Besides, the Eggers test and symmetry in the funnel plot were used to detect the presence/absence of publication bias.

Result
In this meta-analysis, we included 21 articles that assessed 10,090 participants. The average prevalence of depression among people with HIV/AIDS was 35.8% (95% CI 28.29, 43.25). The average estimated prevalence of depressive symptoms was 59.4% in the Oromia region and 29.25% in southern Ethiopia. Besides, the average prevalence of depression was 45.6% and 26.2% as measured with Beck’s depression inventory and Hospital anxiety and depression scale respectively. Moreover, the prevalence of depression was 47.7% in studies that used a sample size ≤ of 400 participants and 28.5% in studies that used a sample size of > 400 participants. The pooled adjusted odds ratio (AOR) of perceived HIV stigma was 3.75 (95% CI 2.34, 5.16) and that of poor social support was 6.22 (95% CI 2.96, 9.47). Moreover, the average odds ratio of poor medication adherence, opportunistic infection, and advanced stages of AIDS were 3.03 (95% CI 1.00, 5.05), 5.5 (95% CI 1.97, 10.03), and 5.43 (95% CI 1.60, 9.28) respectively.

Conclusion
The pooled prevalence of depression among individuals living with HIV/AIDS was high. Factors such as perceived HIV stigma, poor social support, opportunistic infection, advanced AIDS stage, and poor medication adherence were related to it. Routine screening and management of depression and its related factors should be given due consideration.
Attitudes and compliance with the WHO surgical safety checklist: a survey among surgeons and operating room staff in 138 hospitals in China
Authors: Tan Jie , Ngwayi James Reeves Mbori , Ding Zhaohan , Zhou Yufa , Li Ming , Chen Yujie , Hu Bingtao , Liu Jinping , Porter Daniel Edward 
Published: January 2021

Abstract
Background
Ten years after the introduction of the Chinese Ministry of Health (MoH) version of Surgical Safety Checklist (SSC) we wished to assess the ongoing influence of the World Health Organisation (WHO) SSC by observing all three checklist components during elective surgical procedures in China, as well as survey operating room staff and surgeons more widely about the WHO SSC.

Methods
A questionnaire was designed to gain authentic views on the WHO SSC. We also conducted a prospective cross-sectional study at five level 3 hospitals. Local data collectors were trained to document specific item performance. Adverse events which delayed the operation were recorded as well as the individuals leading or participating in the three SSC components.

Results
A total of 846 operating room staff and surgeons from 138 hospitals representing every mainland province responded to the survey. There was widespread acceptance of the checklist and its value in improving patient safety.
860 operations were observed for SSC compliance. Overall compliance was 79.8%. Compliance in surgeon-dependent items of the ‘time-out’ component reduced when it was nurse-led (p < 0.0001). WHO SSC interventions which are omitted from the MoH SSC continued to be discussed over half the time. Overall adverse events rate was 2.7%. One site had near 100% compliance in association with a circulating inspection team which had power of sanction.

Conclusion
The WHO SSC remains a powerful tool for surgical patient safety in China. Cultural changes in nursing assertiveness and surgeon-led teamwork and checklist ownership are the key elements for improving compliance. Standardised audits are required to monitor and ensure checklist compliance.
HOMER3 facilitates growth factor-mediated β-Catenin tyrosine phosphorylation and activation to promote metastasis in triple negative breast cancer
Authors: Liu Qinghua , He Lixin , Li Siqi , Li Fengyan , Deng Guangzheng , Huang Xinjian , Yang Muwen , Xiao Yunyun , Chen Xiangfu , Ouyang Ying , Chen Jinxin , Wu Xuxia , Wang Xi , Song Libing , Lin Chuyong 
Published: January 2021

Abstract
Background
HOMER family scaffolding proteins (HOMER1-3) play critical roles in the development and progression of human disease by regulating the assembly of signal transduction complexes in response to extrinsic stimuli. However, the role of HOMER protein in breast cancer remains unclear.

Methods
HOMER3 expression was examined by immunohistochemistry in breast cancer patient specimens, and its significance in prognosis was assessed by Kaplan–Meier survival analysis. The effects of HOMER3 in growth factor-induced β-Catenin activation were analyzed by assays such as TOP/FOP flash reporter, tyrosine phosphorylation assay and reciprocal immunoprecipitation (IP) assay. Role of HOMER3 in breast cancer metastasis was determined by cell function assays and mice tumor models.

Results
Herein, we find that, among the three HOMER proteins, HOMER3 is selectively overexpressed in the most aggressive triple negative breast cancer (TNBC) subtype, and significantly correlates with earlier tumor metastasis and shorter patient survival. Mechanismly, HOMER3 interacts with both c-Src and β-Catenin, thus providing a scaffolding platform to facilitate c-Src-induced β-Catenin tyrosine phosphorylation under growth factor stimulation. HOMER3 promotes β-Catenin nuclear translocation and activation, and this axis is clinically relevant. HOMER3 promotes and is essential for EGF-induced aggressiveness and metastasis of TNBC cells both in vitro and in vivo.

Conclusion
These findings identify a novel role of HOMER3 in the transduction of growth factor-mediated β-Catenin activation and suggest that HOMER3 might be a targetable vulnerability of TNBC.