bluuebunny/crossref_metadata_2025_split huggingface dataset:
One additional shot of brachial plexus block equates to less postoperative pain for younger children with elbow surgeries
Authors: Li Jin , Rai Saroj , Liu Ruikang , Xu Ruijing , Hong Pan 
Published: July 2020

Abstract
Background
Postoperative pain in children has always been inadequately evaluated. This study aims to evaluate the postoperative pain response using an additional dose of brachial plexus block (BPB) for younger children receiving elbow surgeries under general anesthesia (GA).

Methods
This retrospective case-control study included pediatric patients (3–10 years) who underwent surgeries for elbow injuries between January 2015 and January 2019. Patients with previous history of surgeries around the elbow, neurological impairment of injured limb, polytrauma, undergoing pain management for different causes, and open or old fractures were excluded. Patients were dichotomized into the GA group and the GA + BPB group as per the presence or absence of BPB.

Results
In all, 150 patients (102/48, male/female) in the GA and 150 patients (104/46, male/female) in the GA + BPB group were included. There existed no significant differences between the two groups in age, sex, fracture side, and types of elbow procedures. As for the pain response after lateral condyle fracture of the humerus (LCFH), the FLACC pain scale was significantly higher for those in the GA group (6.2 ± 0.8) when compared to the GA + BPB group (1.6 ± 0.5) (P < 0.001). As for the pain response after medial epicondyle fracture of the humerus (MCFH), the FLACC pain scale was significantly higher for those in the GA group (6.0 ± 0.8) when compared to the GA + BPB group (1.5 ± 0.5) (P < 0.001). As for the pain response after supracondylar fracture of the humerus (SCFH), the FLACC pain scale was significantly higher for those in the GA group (6.0 ± 0.8) when compared to the GA + BPB group (1.6 ± 0.5) (P < 0.001). As for the pain response after cubitus varus correction, the FLACC pain scale was significantly higher for those in the GA group (6.7 ± 0.7) when compared to the GA + BPB group (2.1 ± 0.7) (P < 0.001).

Conclusion
An additional shot of BPB for patients undergoing surgeries for elbow surgeries resulted in better postoperative pain response in younger children without significant BPB-related complications.
Multiple circulating alkaloids and saponins from intravenous Kang-Ai injection inhibit human cytochrome P450 and UDP-glucuronosyltransferase isozymes: potential drug–drug interactions
Authors: Qin Zifei , Jia Mengmeng , Yang Jing , Xing Han , Yin Zhao , Yao Zhihong , Zhang Xiaojian , Yao Xinsheng 
Published: July 2020

Abstract
Background
Kang-Ai injection is widely used as an adjuvant therapy drug for many cancers, leukopenia, and chronic hepatitis B. Circulating alkaloids and saponins are believed to be responsible for therapeutic effects. However, their pharmacokinetics (PK) and excretion in vivo and the risk of drug–drug interactions (DDI) through inhibiting human cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) enzymes remain unclear.

Methods
PK and excretion of circulating compounds were investigated in rats using a validated ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC–MS) method. Further, the inhibitory effects of nine major compounds against eleven CYP and UGT isozymes were assayed using well-accepted specific substrate for each enzyme.

Results
After dosing, 9 alkaloids were found with Cmax and t1/2 values of 0.17–422.70 μmol/L and 1.78–4.33 h, respectively. Additionally, 28 saponins exhibited considerable systemic exposure with t1/2 values of 0.63–7.22 h, whereas other trace saponins could be negligible or undetected. Besides, over 90% of alkaloids were excreted through hepatobiliary and renal excretion. Likewise, astragalosides and protopanaxatriol (PPT) type ginsenosides also involved in hepatobiliary and/or renal excretion. Protopanaxadiol (PPD) type ginsenosides were mainly excreted to urine. Furthermore, PPD-type ginsenosides were extensively bound (fu-plasma approximately 1%), whereas astragalosides and PPT-type ginsenosides displayed fu-plasma values of 12.35% and 60.23–87.36%, respectively. Moreover, matrine, oxymatrine, astragaloside IV, ginsenoside Rg1, ginsenoside Re, ginsenoside Rd, ginsenoside Rc, and ginsenoside Rb1 exhibited no inhibition or weak inhibition against several common CYP and UGT enzymes IC50 values between 8.81 and 92.21 μM. Through kinetic modeling, their inhibition mechanisms towards those CYP and UGT isozymes were explored with obtained Ki values. In vitro-in vivo extrapolation showed the inhibition of systemic clearance for CYP or UGT substrates seemed impossible due to [I]/Ki no more than 0.1.

Conclusions
We summarized the PK behaviors, excretion characteristics and protein binding rates of circulating alkaloids, astragalosides and ginsenosides after intravenous Kang-Ai injection. Furthermore, weak inhibition or no inhibition towards these CYP and UGT activities could not trigger harmful DDI when Kang-Ai injection is co-administered with clinical drugs primarily cleared by these CYP or UGT isozymes.
Characterization of CT scans of patients with Birt-Hogg-Dubé syndrome compared with those of Chinese patients with non-BHD diffuse cyst lung diseases
Authors: Xu Wenshuai , Xu Zhiyan , Liu Yaping , Zhan Yongzhong , Sui Xin , Feng Ruie , Peng Min , Li Xue , Wang Jun , Meng Shuzhen , Wang Li , Tian Xinlun , Zhang Xue , Xu Kai-Feng 
Published: July 2020

Abstract
Background and objective
The purpose of this study was to create a practical CT-based algorithm to differentiate Birt-Hogg-Dubé (BHD) syndrome from other diffuse cystic lung diseases (DCLD).

Methods
The study was a retrospective review of the CT images of 33 patients with BHD syndrome, 33 patients with LAM, and 23 patients with NBNL (non-BHD and non-LAM) among DCLD patients. On the basis of the data collected, the CT images were reviewed again to evaluate the characteristics (size, number, distribution, and morphology) of pulmonary cysts.

Results
Lower lung-predominant cysts were more likely to be found in patients with BHD syndrome than in patients with LAM or in the NBNL DCLD group. In the axial distribution, 18 of 33 patients in BHD group had cysts that were predominantly near the mediastinum, and all the patients in the LAM and NBNL DCLD groups had diffuse cysts. The appearance of fusiform cysts was more easily observed in patients in the BHD group. In total, 58% patients in the BHD group had less than 50 lung cysts, while all patients in the non-BHD group had more than 50 lung cysts. The biggest cyst was located in the lower lobe in 28 of 33 patients in the BHD group, while 11 of 33 patients in LAM group and 10 patients in the NBNL DCLD group had the biggest cyst in the lower lobe.

Conclusion
The pulmonary cysts in patients with BHD tended to be fusiform, less numerous and located predominantly in the lower lobe and near the mediastinum. These radiologic pulmonary features could assist physicians in differentiating BHD from other DCLDs.
In vitro inhibition effects of hepatitis B virus by dandelion and taraxasterol
Authors: Yang Ying , Ying Gaoxiang , Wu Shanshan , Wu Fengtian , Chen Zhi 
Published: July 2020

AbstractHepatitis B virus (HBV) causes hepatitis, which progresses to fatal liver diseases and remains a global health problem. Current treatments for chronic hepatitis B are unable to cure hepatitis. Thus, new antiviral drugs must be developed. In this study, the viral inhibition effects of dandelion and taraxasterol were assessed in HepG2.2.15 cell line. Taraxacum officinale F.H.Wigg. (compositae) with English name dandelion is used as a traditional herb for liver disorders and as a common antiviral agent. Taraxasterol is one of the active compounds of dandelion. The secretion of HBV DNA and HBV surface antigen (HBsAg) and HBeAg was detected using fluorescence quantitative PCR (qPCR) and ELISA, respectively. Intracellular HBsAg was detected by immunofluorescence. In order to demonstrate the potential mechanism of anti-viral activity, the expression levels of host factors polypyrimidine tract binding protein 1 (PTBP1) and sirtuin 1 (SIRT1) were detected with Western blotting and qPCR. Dandelion and taraxasterol effectively reduced the secretion of HBsAg, HBeAg and the HBV DNA in cell supernatants, and significantly reduced the intracellular HBsAg as indicated by immunofluorescence results. Taraxasterol may be one of the main effective components of dandelion. It significantly decreased the protein expression levels of PTBP1 and SIRT1. The present study revealed that dandelion and its component taraxasterol could inhibit HBV and may be a potential anti-HBV drug, whose potential targets were the host factors PTBP1 and SIRT1.
Oral medicinal cannabinoids to relieve symptom burden in the palliative care of patients with advanced cancer: a double-blind, placebo-controlled, randomised clinical trial of efficacy and safety of 1:1 delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD)
Authors: Hardy Janet , Haywood Alison , Gogna Gauri , Martin Jennifer , Yates Patsy , Greer Ristan , Good Phillip 
Published: July 2020

Abstract
Background
Despite improvements in medical care, patients with advanced cancer still experience substantial symptom distress. There is increasing interest in the use of medicinal cannabinoids but little high-quality evidence to guide clinicians. This study aims to define the role of a 1:1 delta-9-tetrahydrocannabinol/cannabidiol (THC/CBD) cannabinoid preparation in the management of symptom burden in patients with advanced cancer undergoing standard palliative care.

Methods and design
One hundred fifty participants will be recruited from five sites within the Queensland Palliative Care Research Group (QPCRG) and randomly assigned to an active treatment or placebo group. This study is a pragmatic multicentre, randomised, placebo-controlled, two-arm trial of escalating doses of an oral 1:1 THC/CBD cannabinoid preparation. It will compare efficacy and safety outcomes of a titrated dose (10 mg/10 mg/mL oral solution formulation, dose range 2.5 mg/2.5 mg–30 mg/30 mg/day) against placebo. There is a 2-week patient-determined titration phase, using escalating doses of 1:1 THC/CBD or placebo, to reach a dose that achieves symptom relief with tolerable side effects. This is then followed by a further 2-week assessment period on the stable dose determined in collaboration with clinicians. The primary objective is to assess the effect of escalating doses of a 1:1 THC/CBD cannabinoid preparation against placebo on change in total symptom score, with secondary objectives including establishing a patient-determined effective dose, the change in total physical and emotional sores, global impression of change, anxiety and depression, opioid use, quality of life and adverse effects.

Discussion
This will be the first placebo-controlled clinical trial to rigorously evaluate the efficacy, safety and acceptability of 1:1 THC/CBD for symptom relief in advanced cancer patients. This study will allow the medical community to have some evidence to present to patients wishing to access cannabis for their symptoms caused by advanced malignancy.

Trial registration
ACTRN, ACTRN12619000037101. Registered on 14 January 2019.
Trial Sponsor: Mater Misericordiae Limited (MML) and Mater Medical Research Institute Limited (MMRI)—Raymond Terrace, South Brisbane, Brisbane, QLD, Australia
Effects of a novel nutraceutical combination (BruMeChol™) in subjects with mild hypercholesterolemia: study protocol of a randomized, double-blind, controlled trial
Authors: Bonfigli Anna Rita , Protic Olga , Olivieri Fabiola , Montesanto Alberto , Malatesta Gelsomina , Di Pillo Raffaele , Antonicelli Roberto 
Published: July 2020

Abstract
Background
Elevated cholesterol levels and systemic inflammation are considered relevant risk factors for cardiovascular disease (CVD) development and progression. Increasing evidence suggests that cholesterol-lowering and inflammation-lowering nutraceuticals are useful in the management of moderate hypercholesterolemia. Here, we describe the study protocol of a clinical trial aimed to evaluate the cholesterol and inflammatory lowering effect of an innovative dietary supplement (BruMeChol™, Mivell S.r.l., Italy), composed of a mixture of extracts of bergamot and olive fruits in association with vitamin K2 in subjects with mild hypercholesterolemia.

Methods
The study was planned as a randomized, double-blind, placebo-controlled, parallel group clinical trial for 12 weeks at the Cardiology Unit of the IRCCS INRCA of Ancona, Italy. A total of 125 subjects (age ≥ 40 years) with mild hypercholesterolemia (total serum cholesterol levels ≥ 200 and ≤ 250 mg/dl) will be recruited. Intervention arm participants will take one capsule of dietary supplement two times a day, 15 min before the main meal. Control arm participants will receive one capsule of placebo in the same way. The dietary supplement capsule contains the following ingredients: phytosterols, flavonoid-rich extract of bergamot fruit (Citrus bergamia), flavonoid-rich extract of olive fruit (Olea europaea), and vitamin K2. Participants will undergo a medical evaluation and chemical-clinical examinations, which include lipid profile, glycemia, biomarkers of renal, liver and cardiac/muscular functions, interleukins (IL 6, IL-32, IL-37, and IL-38), and innovative mediators of inflammation such as inflamma-miRs (miR-21 and miR-146a), at baseline, and after 6 and 12 weeks of treatment. The decrease in total cholesterol levels and inflammatory biomarkers will be the primary and secondary endpoints of the study.

Discussion
This protocol study, planned to verify the effects of BruMeChol™ dietary supplementation in subjects with mild hypercholesterolemia, could also contribute to new study designs for next large-scale multicenter clinical trials.

Trial registration
Australian New Zealand Clinical Trials Registry: ACTRN12619000170123. Retrospectively registered on 5 February 2019
Lipid composition and abundance in the reproductive and alimentary tracts of female Haemonchus contortus
Authors: Wang Tao , Ma Guangxu , Nie Shuai , Williamson Nicholas A. , Reid Gavin E. , Gasser Robin B. 
Published: July 2020

Abstract
Background
Lipids play essential structural and functional roles in the biology of animals. Studying the composition and abundance of lipids in parasites should assist in gaining a better understanding of their molecular biology, biochemistry and host-parasite interactions.

Methods
Here, we used a combination of high-performance liquid chromatography and mass spectrometric analyses, combined with bioinformatics, to explore the lipid composition and abundance in the reproductive (Rt) and alimentary (At) tracts of Haemonchus contortus.

Results
We identified and quantified 320 unique lipid species representing four categories: glycerolipids, glycerophospholipids, sphingolipids and steroid lipids. Glycerolipids (i.e. triradylglycerols) and glycerophospholipids (i.e. glycerophosphocholines) were the most commonly and abundant lipid classes identified and were significantly enriched in Rt and At, respectively. We propose that select parasite-derived lipids in Rt and At of adult female H. contortus are required as an energy source (i.e. triradylglycerol) or are involved in phospholipid biosynthesis (i.e. incorporated fatty acids) and host-parasite interactions (i.e. phospholipids and lysophospholipids).

Conclusions
This work provides a first foundation to explore lipids at the organ-specific and tissue-specific levels in nematodes, and to start to unravel aspects of lipid transport, synthesis and metabolism, with a perspective on discovering new intervention targets.
Non-immune-mediated versus immune-mediated type 1 diabetes: diagnosis and long-term differences—retrospective analysis
Authors: Catarino Diana , Silva Diana , Guiomar Joana , Ribeiro Cristina , Ruas Luísa , Cardoso Luís , Paiva Isabel 
Published: July 2020

Abstract

Background
The American Diabetes Association proposed two subcategories for type 1 diabetes mellitus: type 1A or immune-mediated diabetes (IDM) and type 1B or idiopathic diabetes. The absence of β-cell autoimmune markers, permanent insulinopenia and prone to ketoacidosis define the second category, whose pathogenesis remains unclear. Only a minority of patients fall into this category, also designated non-immune-mediated (NIDM), which is considered by several authors similar to type 2 diabetes. The aim of this study is to evaluate differences at the diagnosis and 10 years later of two categories.

Methods
Retrospective cohort study of patients with β-cell autoimmune markers performed at diagnosis and undetectable c-peptide. Were excluded patients with suspicion of another specific type of diabetes. We obtained two groups: IDM (≥ 1 positive antibody) and NIDM (negative antibodies). Age, family history, anthropometry, duration of symptoms, clinical presentation, blood glucose at admission, A1C, lipid profile, arterial hypertension, total diary insulin dose (TDID), microvascular and macrovascular complications were evaluated. Results were considered statistically significant with p < 0.05.

Results
37 patients, 29 with IDM and 8 patients with NIDM. The age of diagnosis of IDM group (23 years) was significantly different (p = 0.004) from the NIDM group (38.1). The body mass index (BMI) at the diagnosis did not differ significantly (p = 0.435). The duration of symptoms was longer in the NIDM (p = 0.003). The disease presentation (p = 0.744), blood glucose (p = 0.482) and HbA1c (p = 0.794) at admission and TDID at discharge (p = 0.301) did not differ significantly. Total and LDL cholesterol levels were higher in NIDM group but did not differ significantly (p = 0.585 and p = 0.579, respectively). After 10 years BMI did not differ between groups (p = 0.079). Patients with IDM showed a significantly higher HbA1c (p = 0.008) and TDID (p = 0.017). Relative to the lipid profile, there was no significant difference, however the LDL cholesterol and triglycerides were higher on the NIDM group, as the percentage of hypertension. Microvascular complications were higher in the IDM group, but no significant difference was found.

Conclusion
Patients with IDM had a poor metabolic control and higher insulin requirement. Patients with NIDM were older and showed higher cardiovascular risk, resembling a clinical phenotype of type 2 diabetes.
Cathepsin D regulates cerebral Aβ42/40 ratios via differential degradation of Aβ42 and Aβ40
Authors: Suire Caitlin N. , Abdul-Hay Samer O. , Sahara Tomoko , Kang Dongcheul , Brizuela Monica K. , Saftig Paul , Dickson Dennis W. , Rosenberry Terrone L. , Leissring Malcolm A. 
Published: July 2020

Abstract
Background
Cathepsin D (CatD) is a lysosomal protease that degrades both the amyloid β-protein (Aβ) and the microtubule-associated protein, tau, and has been genetically linked to late-onset Alzheimer disease (AD). Here, we sought to examine the consequences of genetic deletion of CatD on Aβ proteostasis in vivo and to more completely characterize the degradation of Aβ42 and Aβ40 by CatD.

Methods
We quantified Aβ degradation rates and levels of endogenous Aβ42 and Aβ40 in the brains of CatD-null (CatD-KO), heterozygous null (CatD-HET), and wild-type (WT) control mice. CatD-KO mice die by ~ 4 weeks of age, so tissues from younger mice, as well as embryonic neuronal cultures, were investigated. Enzymological assays and surface plasmon resonance were employed to quantify the kinetic parameters (KM, kcat) of CatD-mediated degradation of monomeric human Aβ42 vs. Aβ40, and the degradation of aggregated Aβ42 species was also characterized. Competitive inhibition assays were used to interrogate the relative inhibition of full-length human and mouse Aβ42 and Aβ40, as well as corresponding p3 fragments.

Results
Genetic deletion of CatD resulted in 3- to 4-fold increases in insoluble, endogenous cerebral Aβ42 and Aβ40, exceeding the increases produced by deletion of an insulin-degrading enzyme, neprilysin or both, together with readily detectable intralysosomal deposits of endogenous Aβ42—all by 3 weeks of age. Quite significantly, CatD-KO mice exhibited ~ 30% increases in Aβ42/40 ratios, comparable to those induced by presenilin mutations. Mechanistically, the perturbed Aβ42/40 ratios were attributable to pronounced differences in the kinetics of degradation of Aβ42 vis-à-vis Aβ40. Specifically, Aβ42 shows a low-nanomolar affinity for CatD, along with an exceptionally slow turnover rate that, together, renders Aβ42 a highly potent competitive inhibitor of CatD. Notably, the marked differences in the processing of Aβ42 vs. Aβ40 also extend to p3 fragments ending at positions 42 vs. 40.

Conclusions
Our findings identify CatD as the principal intracellular Aβ-degrading protease identified to date, one that regulates Aβ42/40 ratios via differential degradation of Aβ42 vs. Aβ40. The finding that Aβ42 is a potent competitive inhibitor of CatD suggests a possible mechanistic link between elevations in Aβ42 and downstream pathological sequelae in AD.
Fungating malignant peripheral nerve sheath tumor arising from a slow-growing mass in the forearm: a case report and review of the literature
Authors: Abdel Al Samer , Abou Chaar Mohamad K. , Asha Wafa , Al-Najjar Hani , Al-Hussaini Maysa 
Published: July 2020

Abstract
Background
Malignant peripheral nerve sheath tumor is a rare and aggressive form of sarcoma that arises from a peripheral nerve, mostly in association with neurofibromatosis type 1. Half of the cases were reported in the extremities, with the lungs being the most common site of metastasis. We report a rare case of successful limb salvage surgery performed for a large exophytic malignant peripheral nerve sheath tumor of the right forearm with wide surgical margins followed by split-thickness skin graft and later a flexor carpi radialis tendon transfer to extensor digitorum communis tendon.

Case presentation
A 51-year-old Bedouin Arabic man presented to our institution with an incompletely excised, large, fungating, malignant peripheral nerve sheath tumor occupying most of his right forearm. Staging imaging showed multiple lung nodules. He underwent wide local excision followed by skin graft and tendon transfer as a palliative measure to preserve the function of his dominant limb. The operation was performed without any complications, and the patient had an excellent postoperative result. Afterward, he was started on multiple lines of chemotherapy that failed because of disease progression, and the patient died 7 months after the operation.

Conclusion
Clinicians must consider the possibility of soft tissue sarcoma even in a patient with a small, slow-growing, superficial mass. Furthermore, a wrong open biopsy or nononcological surgical procedure may lead to possible contamination and ultimately a more radical procedure than would have originally been necessary, where this can be prevented by an early referral to a highly specialized sarcoma center.