bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can posterior stand-alone expandable cages safely restore lumbar lordosis? A minimum 5-year follow-up study
Authors: Kim Seung-Kook , Elbashier Ogeil Mubarak , Lee Su-chan , Choi Woo-Jin 
Published: September 2020

Abstract
Background
Lumbar lordosis (LL) can be restored, and screw-related complications may be avoided with the stand-alone expandable cage method. However, the long-term spinopelvic changes and safety remain unknown. We aimed to elucidate the long-term radiologic outcomes and safety of this technique.

Methods
Data from patients who underwent multi-level stand-alone expandable cage fusion and 80 patients who underwent screw-assisted fusion between February 2007 and December 2012, with at least 5 years of follow-up, were retrospectively analyzed. Segmental angle and translation, short and whole LL, pelvic incidence, pelvic tilt, sacral slope (SS), sagittal vertical axis, thoracic kyphosis, and presence of subsidence, pseudoarthrosis, retropulsion, cage breakage, proximal junctional kyphosis (PJK), and screw malposition were assessed. The relationship between local, lumbar, and spinopelvic effects was investigated. The implant failure rate was considered a measure of procedure effectiveness and safety.

Results
In total, 69 cases were included in the stand-alone expandable cage group and 150 cases in the control group. The stand-alone group showed shorter operative time (58.48 ± 11.10 vs 81.43 ± 13.75, P = .00028), lower rate of PJK (10.1% vs 22.5%, P = .03), and restoration of local angle (4.66 ± 3.76 vs 2.03 ± 1.16, P = .000079) than the control group. However, sagittal balance (0.01 ± 2.57 vs 0.50 ± 2.10, P = .07) was not restored, and weakness showed higher rate of subsidence (16.31% vs 4.85%, P = .0018), pseudoarthrosis (9.92% vs 2.42%, P = .02), cage, and retropulsion (3.55% vs 0, P = .01) than the control group.

Conclusions
Stand-alone expandable cage fusion can restore local lordosis; however, global sagittal balance was not restored. Furthermore, implant safety has not yet been proven.
Assessment of carotid artery stenosis and lower limb peripheral ischemia before coronary artery bypass grafting operations: a non-randomized clinical trial
Authors: Ali Ihab , Shokri Hoda , Abd Al Jawad Mohammed 
Published: September 2020

Abstract
Background
Atherosclerosis is a systemic disease affecting the coronary, carotid, and lower limb arteries. Cerebrovascular accidents and lower limb ischemia are devastating postoperative complications. We aimed to evaluate the role of non-selective routine arterial duplex scanning in patients undergoing coronary artery bypass grafting (CABG).

Methods
This non-randomized clinical trial included 360 patients scheduled for elective isolated CABG who were divided into two groups: low-risk (n = 180) and high-risk (n = 180). Both groups underwent preoperative carotid and lower limb ultrasound screening for associated arteriopathy.

Results
16 (8.9%) patients and 22 (12.2%) patients showed ≥70% carotid artery stenosis while 11 patients (6.1%) and 20 patients (11.1%) showed ≥50% lower limb arterial stenosis in the low-risk group and the high-risk group, respectively; though the difference was not statistically significant in both the cases (p > 0.1).

Conclusion
Routine preoperative peripheral arterial screening by sonography is a feasible and effective strategy to avoid unnecessary post CABG complications.

Trial registration
NCT03516929, Registered in 24 th of April 2018.
Hejie Zhitong prescription promotes sleep and inhibits nociceptive transmission-associated neurotransmitter activity in a rodent migraine model
Authors: Wang Xinna , Zhao Hongfei , Liu Liming , Niu Ping , Zhai Chao , Li Jinjian , Xu Qiaoli , Zhao Dexi 
Published: September 2020

Abstract
Background
Migraine is painful disease in which neurotransmitters related to pain transmission play an important role. Hejie Zhitong prescription (HJZT) has been used in the clinic as an effective prescription for the treatment of migraine for many years. Our team aimed to further explore its antimigraine mechanism based on previous research results and to explore the inhibitory effect of HJZT on the transmission of pain related to nitroglycerine (NTG)-induced migraine as well as the synergistic effect of HJZT with pentobarbital sodium on promoting sleep.

Methods
Sixty mice were randomly assigned to groups and received the corresponding interventions. Sleep latency and sleep time were recorded to calculate the incidence of sleep. Forty-eight Wistar rats were randomly assigned and administered an intervention corresponding to their group. Calcitonin gene-related peptide (CGRP), serotonin (5-HT), substance P (SP), and cholecystokinin (CCK) levels were measured using ELISAs. Levels of the cannabinoid receptor type 1 (CB1R) and cyclooxygenase-2 (COX-2) protein were assessed using immunohistochemistry. The expression of the CGRP and CCK mRNAs in the midbrain and trigeminal ganglion (TG) were measured using real-time quantitative PCR.

Results
HJZT promoted the occurrence of sleep in mice. HJZT downregulated COX-2 expression in the midbrain and TG of rats but upregulated the expression of the CB1R, and decreased the plasma level of the CGRP protein and expression of its mRNA in the midbrain and TG. It also downregulated the expression of the CCK mRNA in the midbrain and TG. The high-dose HJZT treatment increased plasma 5-HT levels, but did not induce changes in the plasma levels of the SP or CCK protein.

Conclusions
HJZT exerts a synergistic effect with pentobarbital sodium on promoting sleep. As for anti-migraine, HJZT can inhibits the expression of nociceptive transmission-associated neurotransmitters, including 5-HT, CGRP and CCK, which may be related to its upregulation of CB1R and downregulation of COX-2.
Clinical characteristics of patients from Quebec, Canada, with Morquio A syndrome: a longitudinal observational study
Authors: Moisan Lina , Iannuzzi David , Maranda Bruno , Campeau Philippe M. , Mitchell John J. 
Published: September 2020

Abstract
Background
Morquio A syndrome is a rare, autosomal recessive, progressively debilitating disorder, with multi-system impairments and high medical burden. Quebec, Canada has a large Morquio A population, which is considered unique due to the presence of founder pathogenic variants. The objectives of this study were to document the genetic and clinical heterogeneity of patients with Morquio A in Quebec, to better characterize the phenotype of those with the French Canadian founder pathogenic variant (NM_000512.5: c.1171A>G, p.Met391Val), and to describe the natural history of the patients treated with elosulfase alfa enzyme replacement therapy. Patients with Morquio A were genotyped for pathogenic variants in the lysosomal enzyme N-acetylgalactosamine-6-sulfatase. Clinical data were retrospectively collected from medical charts of patients and included medical history, height, physical examination, respiratory function tests, electrocardiogram, echocardiogram, endurance in the 6-min walk test (6MWT), and activities of daily living (ADL) as assessed by the Mucopolysaccharidosis Health Assessment Questionnaire (MPS-HAQ). Longitudinal data were collected retrospectively and prospectively for patients treated with elosulfase alfa.

Results
A total of 33 patients, aged 5–63 years, were included in the analysis. Patients with the founder pathogenic variant (n = 17) generally exhibited a non-classical form of Morquio A. As compared with patients with a non-founder pathogenic variant (n = 16), these patients were generally taller, had greater endurance and were better able to perform ADL. However, they still had significant musculoskeletal disease. Most of the 26 patients treated with elosulfase alfa, regardless of pathogenic variant, showed improvements in endurance and ADL. After 5 to 12 months of treatment, the mean improvement from baseline in the 6MWT was 23% and 10 of 14 patients improved in at least one MPS-HAQ domain. Endurance and ADL generally continued to improve or maintained stable in the long term (up to 7 years). Four out of 19 treated patients with echocardiogram data at follow-up showed progression of cardiac disease.

Conclusions
In Quebec, Canada, Morquio A frequently manifests as a non-classical form of the syndrome due to a founder effect. Patients treated with elosulfase alfa generally show long-term improvement or stability in endurance and function, regardless of pathogenic variant.
Clinical significance of serum anti-granulocyte–macrophage colony-stimulating factor autoantibodies in patients with sarcoidosis and hypersensitivity pneumonitis
Authors: Katayama Kanako , Hirose Masaki , Arai Toru , Hatsuda Kazuyoshi , Tachibana Kazunobu , Sugawara Reiko , Sugimoto Chikatoshi , Kasai Takahiko , Akira Masanori , Inoue Yoshikazu 
Published: September 2020

Abstract
Background
Anti-granulocyte–macrophage colony-stimulating factor autoantibody (GMAb) has been recognized as a diagnostic biomarker for autoimmune pulmonary alveolar proteinosis (aPAP). The aims of this study were to know the incidence of increased level of serum GMAb in granulomatous lung diseases (sarcoidosis and hypersensitivity pneumonitis [HP]) and to clarify the role of GMAb. Consecutive individuals diagnosed with sarcoidosis (n = 92) and HP (n = 45) at National Hospital Organization Kinki-Chuo Chest Medical Center were retrospectively analyzed. We measured serum GMAb levels at the diagnosis. Cut-off values of GMAb discriminating aPAP (n = 110) from healthy controls (n = 31) were determined by receiver operating characteristic (ROC) curve analysis. We compared the clinical features of sarcoidosis and HP patients with GMAb levels above the cut-off value (“Elevated-GMAb”) with those of patients whose GMAb levels below the cut-off value (“Low-GMAb”). Radiological and pathological findings in elevated-GMAb patients were re-evaluated to elucidate the role of GMAb in granulomatous lung diseases.

Results
Analysis of ROC indicated a sensitivity and specificity of 100% at GMAb level of 3.33 μg/mL for discriminating aPAP from healthy controls (area under curve = 1.000, p < 0.0001). The percentages of elevated-GMAb sarcoidosis and HP patients were 5.4% (n = 5) and 11.1% (n = 5), respectively. The number of comorbid sarcoidosis and HP patients with aPAP was two and one, respectively. Elevated-GMAb sarcoidosis patients presented with significantly higher serum levels of Krebs von den Lungen (KL)-6, surfactant protein-D (SP-D), lactate dehydrogenase, and the requirement of systemic corticosteroid therapy. Elevated-GMAb HP patients demonstrated older age, higher serum KL-6, SP-D, carcinoembryonic antigen, and cytokeratin fragment 21-1 levels, and a higher percentage of lymphocytes in bronchoalveolar lavage than low-GMAb patients. A subset of patients presented with radiological and pathological findings characteristic of aPAP.

Conclusions
We demonstrated the percentage of elevated-GMAb sarcoidosis and HP patients who presented with several features suggestive of aPAP. Elevated-GMAb sarcoidosis and HP patients without definitive aPAP diagnosis may have subclinical or early-stage aPAP and may not necessarily indicate false positives. Upon diagnosis of sarcoidosis or HP, measurement of GMAb may be useful in detecting possible comorbidity of subclinical or early-onset aPAP.
The SPARKLE registry: protocol for an international prospective cohort study in patients with alpha-mannosidosis
Authors: Hennermann Julia B. , Guffon Nathalie , Cattaneo Federica , Ceravolo Ferdinando , Borgwardt Line , Lund Allan M. , Gil-Campos Mercedes , Tylki-Szymanska Anna , Muschol Nicole M. 
Published: September 2020

Abstract
Background
Alpha-mannosidosis is a lysosomal storage disorder caused by reduced enzymatic activity of alpha-mannosidase. SPARKLE is an alpha-mannosidosis registry intended to obtain long-term safety and effectiveness data on the use of velmanase alfa during routine clinical care in patients with alpha-mannosidosis. It is a post-approval commitment to European marketing authorization for Velmanase alfa (Lamzede®), the first enzyme replacement therapy for the treatment of non-neurologic manifestations in patients with mild to moderate alpha-mannosidosis. In addition, SPARKLE will expand the current understanding of alpha-mannosidosis by collecting data on the clinical manifestations, progression, and natural history of the disease in treated and untreated patients, respectively.

Results
The SPARKLE registry is designed as a multicenter, multinational, noninterventional, prospective cohort study of patients with alpha-mannosidosis, starting patient enrollment in 2020. Patients will be followed for up to 15 years. Safety and effectiveness as post-authorization outcomes under routine clinical care in patients with treatment will be evaluated. The primary safety outcomes are the rate of adverse events (anti-velmanase alfa-immunoglobulin G antibody development, infusion-related reactions, and hypersensitivity). Secondary safety outcomes include the evaluation of medical events, change in vital signs, laboratory tests, physical examination, and electrocardiogram results. The primary effectiveness outcome is a global treatment response rate, evaluated as the individual aggregate of single endpoints from pharmacodynamic, functional, and quality-of-life effectiveness outcomes; secondary effectiveness outcomes are to characterize the population of patients with alpha-mannosidosis with regard to clinical manifestation, progression, and natural history of the disease. Any patient in the European Union with a diagnosis of alpha-mannosidosis who is willing to participate will likely be eligible for inclusion in the registry. Publications to disseminate scientific insights from the registry are planned.

Conclusion
This study will provide real-world data on the long-term safety and effectiveness of velmanase alfa in patients with alpha-mannosidosis during routine clinical care and increase the understanding of the natural course, clinical manifestations, and progression of this ultra-rare disease.
GPR68 deletion impairs hippocampal long-term potentiation and passive avoidance behavior
Authors: Xu Yuanyuan , Lin Mike T. , Zha Xiang-ming 
Published: September 2020

AbstractIncreased neural activities reduced pH at the synaptic cleft and interstitial spaces. Recent studies have shown that protons function as a neurotransmitter. However, it remains unclear whether protons signal through a metabotropic receptor to regulate synaptic function. Here, we showed that GPR68, a proton-sensitive GPCR, exhibited wide expression in the hippocampus, with higher expression observed in CA3 pyramidal neurons and dentate granule cells. In organotypic hippocampal slice neurons, ectopically expressed GPR68-GFP was present in dendrites, dendritic spines, and axons. Recordings in hippocampal slices isolated from GPR68−/− mice showed a reduced fiber volley at the Schaffer collateral-CA1 synapses, a reduced long-term potentiation (LTP), but unaltered paired-pulse ratio. In a step-through passive avoidance test, GPR68−/− mice exhibited reduced avoidance to the dark chamber. These findings showed that GPR68 contributes to hippocampal LTP and aversive fear memory.
Management of Achilles and patellar tendinopathy: what we know, what we can do
Authors: Aicale Rocco , Oliviero Antonio , Maffulli Nicola 
Published: September 2020

AbstractTendinopathies are challenging conditions frequent in athletes and in middle‐aged overweight patients with no history of increased physical activity. The term “tendinopathy” refers to a clinical condition characterised by pain, swelling, and functional limitations of tendons and nearby structures, the effect of chronic failure of healing response. Tendinopathies give rise to significant morbidity, and, at present, only limited scientifically proven management modalities exist. Achilles and patellar tendons are among the most vulnerable tendons, and among the most frequent lower extremity overuse injuries. Achilles and patellar tendinopathies can be managed primarily conservatively, obtaining good results and clinical outcomes, but, when this approach fails, surgery should be considered. Several surgical procedures have been described for both conditions, and, if performed well, they lead to a relatively high rate of success with few complications. The purpose of this narrative review is to critically examine the recent available scientific literature to provide evidence‐based opinions on these two common and troublesome conditions.
Patient with ovarian insufficiency: baby born after anticancer therapy and re-transplantation of cryopreserved ovarian tissue
Authors: Isachenko Vladimir , Morgenstern Bernd , Todorov Plamen , Isachenko Evgenia , Mallmann Peter , Hanstein Bettina , Rahimi Gohar 
Published: September 2020

Abstract
Background
The second major cause of death is cancer. In fact, the effectiveness of anticancer treatments and positive long-term prognosis for young women has increased. However, the problem of post-cancer infertility plays a significant role, because chemotherapy can be gonadotoxic and lead to the functional death of ovaries. There is potential key solution to this problem: cryopreservation of ovarian tissue before cancer therapy with re-implantation after convalescence. Data regarding cryopreservation and re-transplantation of ovarian tissue from patients with ovarian insufficiency is limited. The aim of this treatment was the re-transplantation of cryopreserved ovarian tissue after anticancer therapy of patient with ovarian insufficiency (56 IU/l FSH, 8 ng/l β-estradiol, < 1.1 ng/ml anti-Mullerian hormone, 1 primary follicle per 10mm3).

Case presentation
After the operation, four tissue fragments (10–16 × 8–13 × 1.0–1.2 mm) were cooled to 5 °C in the freezing medium (culture medium+ 6% ethylene glycol+ 6% dimethyl sulfoxide+ 0.15 M sucrose) for 24 h, frozen and thawed. Freezing was performed in four standard 5 ml cryo-vials with ice formation at − 9 °C, cooling from − 9 to − 34 °C at a rate of − 0.3 °C/min and plunging at − 34 °C into liquid nitrogen. After thawing in a 100 °C (boiling) water bath, the removal of cryoprotectants was performed in 0.5 M sucrose with 20 min. exposure in sucrose and 30 min. stepping rehydration. After thawing of one cryo-vial, part (5 mm3) of experimental ovarian tissue after 7 day in vitro culture was histological evaluated and two ovarian fragments (8 × 7 × 1.0 mm and 7 × 6 × 1.0 mm) were re-transplanted. The quantity of follicles after cryopreservation and in vitro culture was not increased (P > 0.1): it was found 1 primordial follicle in 5 mm3 of tissue. Thirty seven days after the re-transplantation of ovarian tissue, the restoration of the menstrual cycle of Patient W. was noted. Three months after the transplantation, the patient became spontaneously pregnant and delivered a healthy baby girl at term.

Conclusions
Described protocol of conventional cryopreservation of ovarian tissue can be used for treatment of patients with ovarian insufficiency.
Online health information seeking behaviours of parents of children undergoing surgery in a pediatric hospital in Rome, Italy: a survey
Authors: Russo Luisa , Campagna Ilaria , Ferretti Beatrice , Pandolfi Elisabetta , Ciofi Degli Atti Marta Luisa , Piga Simone , Jackson Sally , Rizzo Caterina , Gesualdo Francesco , Tozzi Alberto E. 
Published: September 2020

Abstract
Background
People increasingly search online for health information. Particularly, parents of patients often use the Internet as a source for health information. We conducted a survey to investigate the online searching behavior of parents of patients < 18 years, admitted for surgery in an Italian pediatric hospital.

Methods
The cross-sectional survey was nested in a prospective cohort study on surgical procedures. Parents of patients undergoing surgical procedures at Bambino Gesù Children’s Hospital, Rome, Italy, were enrolled and contacted by phone after the procedure. We recorded socio-demographic data, sex, length of stay following surgery, proximity of residence to the hospital, use of the internet to search for information on the surgery before and after the intervention and effect of information found online.

Results
The majority (91%) of parents of children undergoing surgical intervention used the internet. Of these, 74.3% of parents searched for information before surgery, and 26.1% searched for information after. Most parents searched for information on the care provider’s website. Two thirds of parents reported that information found online had increased their understanding of the child’s condition. Multivariate analyses indicated that families living far from the hospital (> 43 km) were more likely to search for health information (OR 2.3; 95% CI 1.34–4.00), as were families of patients undergoing a major surgery (OR = 2.1; 95% CI 1.04–4.11).

Conclusions
Parents of children undergoing surgery often search online for information on their child’s intervention, in particular those whose child is scheduled for a major surgery and those living far from the hospital. A survey like the present one allows to understand parents’ information needs, to better guide them in online information seeking and to better tailor information provided on the care provider’s website.
Sunitinib facilitates metastatic breast cancer spreading by inducing endothelial cell senescence
Authors: Wang Denian , Xiao Fei , Feng Zhongxue , Li Min , Kong Lingmiao , Huang Luping , Wei Yong’gang , Li Hongyu , Liu Fei , Zhang Haili , Zhang Wei 
Published: September 2020

Abstract
Background
Sunitinib, a receptor tyrosine kinase (RTK) inhibitor that targets multiple receptors such as vascular endothelial growth factor receptors (VEGFRs), was approved for cancer treatment in 2006. However, it was unsuccessful in treating certain cancers, particularly metastatic breast cancer (MBC), and the mechanism underlying this “sunitinib resistance” remains unclear. Herein, we investigated whether the sunitinib-associated inferior survival benefit in MBC was due to sunitinib-induced endothelial cell (EC) injury or EC senescence.

Methods
4T1 murine breast cancer cells were used as the main breast tumor model for it produces a highly metastatic solid tumor that can spontaneously metastasize to the lung, which closely mimics highly metastatic human breast cancer. Senescence-associated β-galactosidase (SA-β-Gal, immunohistochemistry [IHC]-staining), P16, P53, and P57 (immunoblotting) were used as markers of cell senescence. A protein array containing 25 senescence-associated chemokines and the transwell chemotaxis assay were used to examine whether sunitinib increases inflammatory chemokine secretion which attracts tumor cells via chemokinesis. Flow cytometry and IHC were used to detect whether the sunitinib-induced senescent ECs recruit cancer-associated inflammatory myeloid cells. Finally, the spontaneous metastatic model was used to monitor whether sunitinib causes the formation of “pre-metastatic niche” which promotes MBC to metastasize to the lungs.

Results
We demonstrated that sunitinib induced a senescence-like endothelial cell (EC) phenotype. Inflammatory chemokine secretion and VCAM1 expression were significantly increased in senescent ECs, resulting in tumor cell (TC) chemotaxis and TC/EC interactions. Meanwhile, EC senescence caused loosening of EC junctions, facilitating TC transmigration through the endothelial barrier. Sunitinib-induced senescent ECs also recruited cancer-associated myeloid cells to form a “pre-metastatic niche”-like microenvironment. Alterations at the molecular level and in the tissue environment ultimately led to an increase in distant metastasis.

Conclusion
Although sunitinib was designed to target the EC directly, the increase in tumor metastasis may ironically be due to sunitinib “correctly” playing its role. Our findings suggest that we should carefully weigh the pros and cons before using sunitinib and other antiangiogenic drugs that directly target the ECs.