bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rates, costs, return to work and reoperation following spinal surgery in a workers’ compensation cohort in New South Wales, 2010–2018: a cohort study using administrative data
Authors: Lewin AM , Fearnside M , Kuru R , Jonker BP , Naylor JM , Sheridan M , Harris IA 
Published: September 2021

Abstract
Background
Internationally, elective spinal surgery rates in workers’ compensation populations are high, as are reoperation rates, while return-to-work rates following spinal surgery are low. Little information is available from Australia. The aim of this study was to describe the rates, costs, return to work and reoperation following elective spinal surgery in the workers’ compensation population in New South Wales (NSW), Australia.

Methods
This retrospective cohort study used administrative data from the State Insurance Regulatory Authority, the government organisation responsible for regulating and administering workers’ compensation insurance in NSW. These data cover all workers’ compensation-insured workers in New South Wales (over 3 million workers/year). We identified a cohort of insured workers who underwent elective spinal surgery (fusion or decompression) between January 1, 2010 and December 31, 2018. People who underwent surgery for spinal fracture or dislocation, or who had sustained a traumatic brain injury were excluded. The main outcome measures were annual spinal surgery rates, cost of the surgical episode, cumulative costs (surgical, hospital, medical and physical therapy) to 2 years post-surgery, and reoperation and return-to-work rates 2 years post-surgery.

Results
There were 9343 eligible claims (39.1 % fusion; 59.9 % decompression); claimants were predominantly male (75 %) with a mean age of 43 (range 18 to 75) years. Spinal surgery rates ranged from 15 to 29 surgeries per 100,000 workers per year, fell from 2011-12 to 2014-15 and rose thereafter. The average cost in Australian dollars for a surgical episode was $46,000 for a spinal fusion and $20,000 for a decompression. Two years post-fusion, only 19 % of people had returned to work at full capacity; 39 % after decompression. Nineteen percent of patients underwent additional spinal surgery within 2 years of the index surgery, to a maximum of 5 additional surgeries.

Conclusion
Rates of workers’ compensation-funded spinal surgery did not rise significantly during the study period, but reoperation rates are high and return-to-work rates are low in this population at 2 years post- surgery. In the context of the poor evidence base supporting lumbar fusion surgery, the high cost, increasing rates, and the increased likelihood of poor outcomes in the workers’ compensation population, we question the value of this procedure in this setting.
Changes in pediatric hospital care during the COVID-19 pandemic: a national qualitative study
Authors: Penwill Nicole Y. , Roessler De Angulo Nadia , Pathak Priya R. , Ja Clairissa , Elster Martha J. , Hochreiter Daniela , Newton Jacqueline M. , Wilson Karen M. , Kaiser Sunitha V. 
Published: September 2021

Abstract
Background
The COVID-19 pandemic has necessitated rapid changes in healthcare delivery in the United States, including changes in the care of hospitalized children. The objectives of this study were to identify major changes in healthcare delivery for hospitalized children during the COVID-19 pandemic, identify lessons learned from these changes, and compare and contrast the experiences of children’s and community hospitals.

Methods
We purposefully sampled participants from both community and children’s hospitals serving pediatric patients in the six U.S. states with the highest COVID-19 hospitalization rates at the onset of the pandemic. We recruited 2–3 participants from each hospital (mix of administrators, front-line physicians, nurses, and parents/caregivers) for semi-structured interviews. We analyzed interview data using constant comparative methods to identify major themes.

Results
We interviewed 30 participants from 12 hospitals. Participants described how leaders rapidly developed new hospital policies (e.g., directing use of personal protective equipment) and how this was facilitated by reviewing internal and external data frequently and engaging all relevant stakeholders. Hospital leaders optimized communication through regular, transparent, multi-modal, and bi-directional communication. Clinicians increased use of videoconference and telehealth to facilitate physical distancing, but these technologies may have disadvantaged non-English speakers. Due to declining volumes of hospitalized children and surges of adult patients, clinicians newly provided care for hospitalized adults. This was facilitated by developing care teams supported by adult hospitalists, multidisciplinary support via videoconference, and educational resources. Participants described how the pandemic negatively impacted clinicians’ mental health, and they stressed the importance of mental health resources and wellness activities/spaces.

Conclusions
We identified several major changes in inpatient pediatric care delivery during the COVID-19 pandemic, including the adoption of new hospital policies, video communication, staffing models, education strategies, and staff mental health supports. We outline important lessons learned, including strategies for successfully developing new policies, effectively communicating with staff, and supporting clinicians’ expanding scope of practice. Potentially important focus areas in pandemic recovery include assessing and supporting clinicians’ mental health and well-being, re-evaluating trainees’ skills/competencies, and adapting educational strategies as needed. These findings can help guide hospital leaders in supporting pandemic recovery and addressing future crises.
Patient gender does not influence referral to an orthopaedic surgeon by advanced practice orthopaedic providers: a prospective observational study in Canada
Authors: Robarts Susan , Denis Suzanne , Kennedy Deborah , Dickson Patricia , Juma Shahiroz , Palinkas Veronica , Rachevitz Maria , Boljanovic-Susic Dragana , Stratford Paul 
Published: September 2021

Abstract
Background
The role of an advanced practice physiotherapist has been introduced in many countries to improve access to care for patients with hip and knee arthritis. Traditional models of care have shown a gender bias, with women less often referred and recommended for surgery than men. This study sought to understand if patient gender affects access to care in the clinical encounter with the advanced practice provider. Our objectives were: (1) To determine if a gender difference exists in the clinical decision to offer a consultation with a surgeon; (2) To determine if a gender difference exists in patients’ decisions to accept a consultation with a surgeon among those patients to whom it is offered; and, (3) To describe patients’ reasons for not accepting a consultation with a surgeon.

Methods
This was a prospective study of 815 patients presenting to a tertiary care centre for assessment of hip and knee arthritis, with referral onward to an orthopaedic surgeon when indicated. We performed a multiple logistic regression analysis adjusting for severity to address the first objective and a simple logistic regression analysis to answer the second objective. Reasons for not accepting a surgical consultation were obtained by questionnaire.

Results
Eight hundred and fifteen patients (511 women, 304 men) fulfilled study eligibility criteria. There was no difference in the probability of being referred to a surgeon for men and women (difference adjusted for severity = − 0.02, 95% CI: − 0.07, 0.02). Neither was there a difference in the acceptance of a referral for men and women (difference = − 0.05, 95% CI: − 0.09, 0.00). Of the 14 reasons for declining a surgical consultation, 5 showed a difference with more women than men indicating a preference for non-surgical treatment along with fears/concerns about surgery.

Conclusions
There is no strong evidence to suggest there is a difference in proportion of males and females proceeding to surgical consultation in the model of care that utilizes advanced practice orthopaedic providers in triage. This study adds to the evidence that supports the use of suitably trained alternate providers in roles that reduce wait times to care and add value in contexts where health human resources are limited. The care model is a viable strategy to assist in managing the growing backlog in orthopaedic care, recently exacerbated by the COVID-19 pandemic.
Sequencing of neurofilament genes identified NEFH Ser787Arg as a novel risk variant of sporadic amyotrophic lateral sclerosis in Chinese subjects
Authors: Lin Feng , Lin Wanhui , Zhu Chaofeng , Lin Jilan , Zhu Junge , Li Xu-Ying , Wang Zhanjun , Wang Chaodong , Huang Huapin 
Published: September 2021

Abstract
Background
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease with neuronal cell inclusions composed of neurofilaments and other abnormal aggregative proteins as pathological hallmarks. Approximately 90% of patients have sporadic cases (sALS), and at least 4 genes, i.e. C9orf72, SOD1, FUS and TARDBP, have been identified as the main causative genes, while many others have been proposed as potential risk genes. However, these mutations could explain only ~ 10% of sALS cases. The neurofilament polypeptides encoded by NEFH, NEFM, and NEFL are promising protein biomarkers for ALS and other degenerative diseases. However, whether the genetic variants of these genes were associated with ALS remain ambiguous.

Methods
Here, we used PCR-Sanger to sequence the exons of these three genes in a cohort of 371 sALS patients and 711 healthy controls (Phase I) and validated the risk variant in another 300 sALS patients and 1076 controls (Phase II).

Results
A total of 92 variants were identified, including 36 rare heterozygous variants in NEFH, 27 in NEFM, and 16 in NEFL, and only rs568759161 (p.Ser787Arg) in NEFH reached nominal statistical power (P = 0.02 at Phase I, P = 0.009 at Phase II) in the case–control comparison. Together, the Phase I and II studies showed the significantly higher frequency of the variant in cases (9/1342, 0.67%) than in controls (2/3574, 0.07%) (OR 12.06; 95% CI 2.60–55.88; P = 0.0003). No variants passed multiple testing in the discovery cohort, but rs568759161 was associated with ALS in a replication cohort.

Conclusions
Our results confirmed that NEFH Ser787Arg is a novel sALS risk variant in Chinese subjects, but NEFM and NEFL were not associated with sALS. These data may have implications for genetic counselling and for understanding the pathogenesis of sALS.
Effect of alirocumab on coronary plaque in patients with coronary artery disease assessed by optical coherence tomography
Authors: Gao Fei , Wang Zhi Jian , Ma Xiao Teng , Shen Hua , Yang Li Xia , Zhou Yu Jie 
Published: September 2021

Abstract
Background
Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors have been demonstrated to produce significantly greater reduction in LDL cholesterol levels and cardiovascular events than standard statin therapy. However, evidence on the impact of PCSK9 inhibitors on coronary plaque composition and morphology is limited.

Methods
In this open-label randomized study, eligible patients with intermediate coronary lesions and elevated LDL cholesterol values were randomized to either alirocumab 75 mg Q2W plus statin (atorvastatin 20 mg/day or rosuvastatin 10 mg/day) therapy or standard care. Optical coherence tomography (OCT) assessments for target lesions were obtained at baseline and at 36 weeks of follow-up.

Results
LDL cholesterol levels were significantly decreased in both the alirocumab and standard care arms, whereas the absolute reduction in LDL cholesterol was significantly greater in patients treated with alirocumab (1.72 ± 0.51 vs. 0.96 ± 0.59, P < 0.0001). Compared with standard care, the addition of alirocumab to statins was associated with significantly greater increases in minimum fibrous cap thickness (18.0 [10.8–29.2] μm vs 13.2 [7.4–18.6] μm; P = 0.029), greater increases in minimum lumen area (0.20[0.10–0.33] mm2 vs 0.13 [0.12–0.24] mm2; P = 0.006) and a greater diminution in maximum lipid arc (15.1̊ [7.8–24.5] vs. 8.4̊ [2.0–10.5]; P = 0.008).

Conclusions
The addition of alirocumab to statins can not only provide additional LDL cholesterol lowering effects but also have a potential role in promoting a more stable plaque phenotype.

Trial registration
ClinicalTrials.gov Identifier: NCT04851769. Registered 2 Mar 2019.
Inverted U-shaped correlation between serum low-density lipoprotein cholesterol levels and cognitive functions of patients with type 2 diabetes mellitus
Authors: Zhang Haoqiang , Zhu Wenwen , Niu Tong , Wang Zheng , An Ke , Cao Wuyou , Shi Jijing , Wang Shaohua 
Published: September 2021

Abstract
Background
Low-density lipoprotein cholesterol (LDL-C) metabolic disorder is common in individuals with diabetes. The role of LDL-C in mild cognitive impairment (MCI) remains to be explored. We aim to investigate the associations between LDL-C at different levels and details of cognition decline in patients with type 2 diabetes mellitus (T2DM).

Methods
Patients with T2DM (n = 497) were recruited. Clinical parameters and neuropsychological tests were compared between patients with MCI and controls. Goodness of fit was assessed to determine the linear or U-shaped relationship between LDL-C and cognitive function. The cut-off point of LDL-C was calculated. Correlation and regression were carried out to explore the relationship between cognitive dysfunction and LDL-C levels above and below the cut-off point.

Results
Although no significant difference in LDL-C levels was detected in 235 patients with MCI, compared with 262 patients without MCI, inverted-U-shaped association was determined between LDL-C and Montreal Cognitive Assessment (MoCA). The cut-off point of LDL-C is 2.686 mmol/l. LDL-C (>2.686 mmol/l) is positively related to Trail Making Test B (TMTB) indicating executive function. LDL-C (<2.686 mmol/l) is positively associated with Clock Drawing Test (CDT) reflecting visual space function in patients with T2DM.

Conclusion
Inverted U-shaped correlation was found between serum LDL-C and cognitive function in patients with T2DM. Despite that the mechanisms of different LDL-C levels involved in special cognitive dysfunctions remain incompletely clarified, excessive LDL-C damages executive function, while the deficient LDL-C impairs visual space function.

Trial registration
ChiCTR-OCC-15006060.
The LDLR c.501C>A is a disease-causing variant in familial hypercholesterolemia
Authors: Hu Haochang , Chen Ruoyu , Hu Yingchu , Wang Jian , Lin Shaoyi , Chen Xiaomin 
Published: September 2021

Abstract
Background
As an autosomal dominant disorder, familial hypercholesterolemia (FH) is mainly attributed to disease-causing variants in the low-density lipoprotein receptor (LDLR) gene. The aim of this study was to explore the molecular mechanism of LDLR c.501C>A variant in FH and assess the efficacy of proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor treatment for FH patients.

Methods
The whole-exome sequencing was performed on two families to identify disease-causing variants, which were verified by Sanger sequencing. The function of LDLR variant was further explored in HEK293 cells by Western Blot and confocal microscopy. Besides, the therapeutic effects of PCSK9 inhibitor treatment for two probands were assessed for 3 months.

Results
All members of the two families with the LDLR c.501C>A variant showed high levels of LDLC. The relationship between the clinical phenotype and LDLR variants was confirmed in the current study. Both in silico and in vitro analyses showed that LDLR c.501C>A variant decreased LDLR expression and LDL uptake. PCSK9 inhibitor treatment lowered the lipid level in proband 1 by 24.91%. However, the treatment was ineffective for proband 2. A follow-up study revealed that the PCSK9 inhibitor treatment had low ability of lipid-lowering effect in the patients.

Conclusions
LDLR c.501C>A variant might be pathogenic for FH. The PCSK9 inhibitor therapy is not a highly effective option for treatment of FH patients with LDLR c.501C>A variant.
Expression and prognostic significance of Niemann-Pick C1-Like 1 in colorectal cancer: a retrospective cohort study
Authors: Kwon Ryuk Jun , Park Eun-Ju , Lee Sang Yeoup , Lee Youngin , Hwang Chungsu , Kim Choongrak , Cho Young Hye 
Published: September 2021

Abstract
Background
Colorectal cancer (CRC) is a malignancy of the large intestine, whose development and prognosis have been demonstrated to be associated with altered lipid metabolism. High cholesterol intake is associated with an increased risk of CRC, and elevated serum cholesterol levels are known to be correlated with risk of developing CRC. Niemann-Pick C1-Like 1 (NPC1L1), a target of ezetimibe, plays an essential role in the absorption of intestinal cholesterol. However, whether the altered expression of NPC1L1 affects CRC development and prognosis is currently unknown.

Methods
Data corresponding to patients with CRC were obtained from The Cancer Genome Atlas (TCAG). Datasets from the Genome Data Analysis Center (GDAC) platform were analyzed to compare the expression of NPC1L1 in normal and CRC tissues using the Mann–Whitney U test and chi-square test. Further, the datasets from the Gene Expression Omnibus (GEO) database were analyzed. The log-rank test and multivariate Cox proportional hazard regression analysis were performed to determine whether NPC1L1 significantly affects the prognosis of CRC.

Results
The expression of NPC1L1 was found to be upregulated in CRC and was significantly associated with the N and pathological stages but not with the histological type, age, and sex. Increased NPC1L1 expression in CRC was related to poor patient survival, as evidenced by the Kaplan–Meier and multivariate regression analyses.

Conclusions
As high expression of NPC1L1 was associated with CRC development, pathological stage, and prognosis, NPC1L1 can serve as an independent prognostic marker for CRC.
Fully hydrogenated canola oil extends lifespan in stroke-prone spontaneously hypertensive rats
Authors: Tatematsu Kenjiro , Miyazawa Daisuke , Saito Yoshiaki , Okuyama Harumi , Ohara Naoki 
Published: September 2021

Abstract
Background
Canola oil (Can) and several vegetable oils shorten the lifespan of stroke-prone spontaneously hypertensive rats (SHRSP). Although similar lifespan shortening has been reported for partially hydrogenated Can, the efficacy of fully hydrogenated oils on the lifespan remains unknown. The present study aimed to investigate the lifespan of SHRSP fed diets containing 10 % (w/w) of fully hydrogenated Can (FHCO) or other oils.

Methods
Survival test: Upon weaning, male SHRSP were fed a basal diet for rodents mixed with one of the test oils —i.e., FHCO, Can, lard (Lrd), and palm oil (Plm) throughout the experiment. The animals could freely access the diet and drinking water (water containing 1 % NaCl), and their body weight, food intake, and lifespan were recorded.
Biochemical analysis test: Male SHRSP were fed a test diet with either FHCO, Can, or soybean oil (Soy) under the same condition, except to emphasize effects of fat, that no NaCl loading was applied. Soy was used as a fat source in the basal diet and was set the control group. Blood pressures was checked every 2 weeks, and serum fat levels and histological analyses of the brain and kidney were examined after 7 or 12 weeks of feeding.

Results
During the survival study period, the food consumption of FHCO-fed rats significantly increased (15–20 % w/w) compared with that of rats fed any other oil. However, the body weight gain in the FHCO group was significantly less (10–12 %) than that in the control group at 9–11 weeks old. The FHCO (> 180 days) intervention had the greatest effect on lifespan, followed by the Lrd (115 ± 6 days), Plm (101 ± 2 days), and Can (94 ± 3 days) diets. FHCO remarkably decreased the serum cholesterol level compared with Can and the systolic blood pressure from 12 to 16 weeks of age. In addition, while some rats in the Can group exhibited brain hemorrhaging and renal dysfunction at 16 weeks old, no symptoms were observed in the FHCO group.

Conclusion
This current study suggests that complete hydrogenation decreases the toxicity of Can and even prolongs the lifespan in SHRSP.
Plasma neurofilament light chain level predicts outcomes in stroke patients receiving endovascular thrombectomy
Authors: Chen Chih-Hao , Chu Hai-Jui , Hwang Yi-Ting , Lin Yen-Heng , Lee Chung-Wei , Tang Sung-Chun , Jeng Jiann-Shing 
Published: September 2021

Abstract
Background
Timely endovascular thrombectomy (EVT) significantly improves outcomes in patients with acute ischemic stroke (AIS) with large vessel occlusion type. However, whether certain central nervous system-specific plasma biomarkers correlate with the outcomes is unknown. We evaluated the temporal changes and prognostic roles of the levels of these biomarkers in patients with AIS undergoing EVT.

Methods
We enrolled 60 patients who received EVT for AIS and 14 controls. The levels of plasma biomarkers, namely neurofilament light chain (NfL), glial fibrillary astrocytic protein (GFAP), tau, and ubiquitin C-terminal hydrolase L1 (UCHL1), were measured with an ultrasensitive single molecule array before, immediately after, and 24 h after EVT (T1, T2, and T3, respectively). The outcomes of interest were death or disability at 90 days (defined as a modified Rankin Scale score of 3–6) and types of hemorrhagic transformation (hemorrhagic infarction or parenchymal hemorrhage).

Results
Of the 180 blood samples from the 60 patients who received EVT, the plasma NfL, GFAP, and UCHL1 levels at T1 were significantly higher than those of the controls, and the levels of all four biomarkers were significantly higher at T3. Patients with parenchymal hemorrhage had a significantly higher rate of increase in GFAP (Pinteraction = 0.005) and UCHL1 (Pinteraction = 0.007) levels compared with those without parenchymal hemorrhage. In a multivariable analysis with adjustment for age, sex, National Institute of Health Stroke Scale score, history of atrial fibrillation, and recanalization status, higher NfL levels at T1 (odds ratio [OR] 2.05; 95% confidence interval [CI], 1.03–4.08), T2 (OR, 2.08; 95% CI, 1.05–4.01), and T3 (OR, 3.94; 95% CI, 1.44–10.79) were independent predictors of death or disability at 90 days.

Conclusion
Among patients with AIS who received EVT, those with hemorrhagic transformation exhibited significant increase in plasma GFAP and UCHL1 levels over time. Higher plasma NfL were predictive of unfavorable functional outcomes.