bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nicotinamide riboside as a neuroprotective therapy for glaucoma: study protocol for a randomized, double-blind, placebo-control trial
Authors: Leung Christopher Kai Shun , Ren Seraph Tianmin , Chan Poemen Pui Man , Wan Kelvin Ho Nam , Kam Aziz Ka Wai , Lai Gilda Wing Ki , Chiu Vivian Sheung Man , Ko Match Wai Lun , Yiu Cedric Ka Fai , Yu Marco Chak Yan 
Published: January 2022

Abstract
Background
Whereas lowering the intraocular pressure (IOP) can slow optic nerve degeneration in glaucoma, many patients with glaucoma continue to develop progressive loss in vision despite a significant reduction in IOP. No treatment has been shown to be effective for neuroprotection in glaucoma. We set out to conduct a randomized controlled trial to investigate whether nicotinamide riboside (NR), a nicotinamide adenine dinucleotide precursor, is effective to slow optic nerve degeneration in patients with primary open-angle glaucoma (POAG). We hypothesize that patients treated with NR have a slower rate of progressive retinal nerve fiber layer (RNFL) thinning compared with those treated with placebo.

Methods
This is a randomized, double-blind, placebo-controlled, parallel-group, multi-center study including 125 patients with POAG. Patients will be randomized to receive 300 mg NR or placebo for 24 months. Clinical examination, optical coherence tomography imaging of the RNFL, and visual field (VF) test will be performed at the baseline, 1 month, 4 months, and then at 2-month intervals until 24 months. The primary outcome measure is the rate of RNFL thinning measured over 24 months. The secondary outcome measures include (1) time to VF progression, (2) time to progressive RNFL/ganglion cell inner plexiform layer (GCIPL) thinning, and (3) the rate of change of VF sensitivity over 24 months (to investigate neuroprotection) and 1 month (to investigate neuroenhancement). The rates of RNFL thinning and VF sensitivity decline between treatment groups will be compared with linear mixed modeling. Survival analysis will be performed to compare the differences in time from baseline to VF progression and time from baseline to progressive RNFL/GCIPL thinning between treatment groups using Cox proportional hazards models.

Discussion
Outcome measures in glaucoma neuroprotection trials have been centered on the detection of VF progression, which may take years to develop and confirm. In addition to addressing whether NR has a neuroprotective/neuroenhancement effect in glaucoma patients, this study will demonstrate the feasibility of studying neuroprotection in a relatively short trial period (24 months) by comparing the rates of progressive RNFL thinning, a more reproducible and objective outcome measure compared with VF endpoints, between treatment groups.

Trial registration
Chinese Clinical Trial Registry 1900021998
An enhanced participant information leaflet and multimedia intervention to improve the quality of informed consent to a randomised clinical trial enrolling people living with HIV and obesity: a protocol for a Study Within A Trial (SWAT)
Authors: O’Sullivan Lydia , Savinelli Stefano , O’Hare Stephen , Holden Sinéad , McHugh Ciara , Mallon Patrick , Doran Peter 
Published: January 2022

AbstractBackgroundIt is the investigator’s responsibility to communicate the relevant information about a clinical trial to participants before they provide informed consent to take part. Systematic reviews indicate that participants often have a poor understanding of the concepts which are key to ensuring valid informed consent, such as randomisation and risks/discomforts. Paper-based participant information leaflets and informed consent forms (PIL/ICFs) are becoming longer and are often too complex for many participants. Multimedia interventions and enhanced PIL/ICFs have been trialled in an attempt to improve participants’ understanding of various aspects of research studies. However, there is insufficient empirical evidence to determine how effective such interventions are. This protocol describes a study to evaluate whether an enhanced PIL/ICF and website help research participants to understand important information about a human immunodeficiency virus (HIV) randomised clinical trial.MethodsThis Study Within A Trial (SWAT) is a prospective, multi-centre, randomised, controlled, parallel-group study embedded in a host clinical trial. The host trial (the SWIFT trial; EudraCT: 2019-002314-39) is a prospective, multi-centre, randomised, open-label, controlled trial investigating if semaglutide along with dietary advice assists individuals with HIV and obesity to lose weight, compared to dietary advice alone. For the SWAT, participants will be randomised in a 1:1 ratio to either the control (standard PIL/ICF) or the intervention (an enhanced PIL/ICF and a website which includes animations). The enhanced PIL/ICF and website were developed in line with the guidance from organisations which promote plain English and accessible public-facing materials in conjunction with HIV Ireland, a HIV advocacy organisation, and our previous work on consent documents. The primary outcome of the SWAT is the quality of informed consent, assessed by a validated comprehension test—the modified Deaconess Informed Consent Comprehension Test (DICCT). The DICCT will be administered within 48 h of consent to the host trial. The secondary is recall, measured by the modified DICCT questionnaire scores 2 weeks post-consent to the host trial.DiscussionThe results of this SWAT will add to the methodological evidence base on the use of multimedia to improve the quality of informed consent to randomised clinical trials.Trial registrationClinicalTrials.govNCT04174755. EudraCT 2019-002314-39. SWAT 160, Northern Ireland Hub for Trials Methodology Research SWAT repository (Clarke M, et al., Trials. 16:P209, 2015).
Fibrotic alterations in human annulus fibrosus correlate with progression of intervertebral disc herniation
Authors: Castro A. L. , Ribeiro-Machado C. , Oliveira C. M. , Teixeira G. Q. , Neidlinger-Wilke C. , Pereira P. , Vaz R. , Barbosa M. A. , Gonçalves R. M. 
Published: January 2022

Abstract
Background
Intervertebral disc (IVD) herniation is characterized by annulus fibrosus failure (AF) in containing the nucleus pulposus (NP). IVD herniation involves cellular and extracellular matrix (ECM) alterations that have been associated with tissue fibrosis, although still poorly investigated.

Methods
Here, fibrotic alterations in human AF were evaluated, by characterizing the herniated ECM. Human AF samples (herniated lumbar IVD (n = 39, age 24–83) and scoliosis controls (n = 6, age 15–21)) were processed for transmission electron microscopy and histological/immunohistochemical analysis of fibrotic markers. Correlations between the fibrotic markers in AF ECM and the degree of NP containment (protused, contained and uncontained) and patients’ age were conducted.

Results
Our results demonstrate that with herniation progression, i.e. loss of NP containment, human AF presents less stained area of sulphated glycosaminoglycans and collagen I, being collagen I fibres thinner and disorganized. On the other hand, fibronectin stained area and percentage of α-smooth muscle actin+ cells increase in human AF, while matrix metalloproteinase-12 (MMP12) production and percentage of macrophages (CD68+ cells) remain constant. These structural and biochemical fibrotic alterations observed in human AF with herniation progression occur independently of the age.

Conclusions
The characterization of human AF here conducted evidence the presence of fibrosis in degenerated IVD, while highlighting the importance of considering the herniation progression stage, despite the patients’ age, for a better understanding of the mechanisms behind AF failure and IVD herniation.
A role for neutrophils in early enthesitis in spondyloarthritis
Authors: Stavre Zheni , Bridgewood Charles , Zhou Qiao , Maeda Yukiko , Huang Ting-ting , Karman Jozsef , Khan Almas , Giryes Sami , Sharif Kassem , McGonagle Dennis , Gravallese Ellen M. 
Published: January 2022

AbstractBackgroundNeutrophils are present in the early phases of spondyloarthritis-related uveitis, skin and intestinal disease, but their role in enthesitis, a cardinal musculoskeletal lesion in spondyloarthritis, remains unknown. We considered the role of neutrophils in the experimental SKG mouse model of SpA and in human axial entheses.MethodsEarly inflammatory infiltrates in the axial and peripheral entheseal sites in SKG mice were evaluated using immunohistochemistry and laser capture microdissection of entheseal tissue. Whole transcriptome analysis was carried out using Affymetrix gene array MTA 1.0, and data was analyzed via IPA. We further isolated neutrophils from human peri-entheseal bone and fibroblasts from entheseal soft tissue obtained from the axial skeleton of healthy patients and determined the response of these cells to fungal adjuvant.ResultsFollowing fungal adjuvant administration, early axial and peripheral inflammation in SKG mice was characterized by prominent neutrophilic entheseal inflammation. Expression of transcripts arising from neutrophils include abundant mRNA for the alarmins S100A8 and S100A9. In normal human axial entheses, neutrophils were present in the peri-entheseal bone. Upon fungal stimulation in vitro, human neutrophils produced IL-23 protein, while isolated human entheseal fibroblasts produced chemokines, including IL-8, important in the recruitment of neutrophils.ConclusionNeutrophils with inducible IL-23 production are present in uninflamed human entheseal sites, and neutrophils are prominent in early murine spondyloarthritis-related enthesitis. We propose a role for neutrophils in the early development of enthesitis.
Locally advanced gallbladder cancer treated with effective chemotherapy and subsequent curative resection: a case report
Authors: Inoue Masashi , Hakoda Keishi , Sawada Hiroyuki , Hotta Ryuichi , Ohmori Ichiro , Miyamoto Kazuaki , Toyota Kazuhiro , Sadamoto Seiji , Takahashi Tadateru 
Published: January 2022

Abstract
Background
Surgical resection of gallbladder cancer with negative margins is the only potentially curative therapy. Most patients with gallbladder cancer are diagnosed in an advanced stage and, despite the availability of several chemotherapies, the prognosis remains dismal. We report a case of locally advanced gallbladder cancer that was successfully treated with effective cisplatin plus gemcitabine, followed by curative resection.

Case presentation
A 55-year-old Japanese female was hospitalized with right hypochondrial pain. Enhanced computed tomography revealed a 49 × 47 mm mass at the neck of the gallbladder, with suspected invasion of the liver and right hepatic artery. Endoscopic retrograde cholangiopancreatography demonstrated displacement of the upper bile duct. Intraductal ultrasonography showed irregular wall thickening and disappearance of the wall structure in bile ducts from the B4 branch to distal B2 and B3. Percutaneous transhepatic biliary biopsy revealed a poorly differentiated carcinoma. The patient was diagnosed with unresectable gallbladder cancer (T4N0M0 stage IVA). Cisplatin plus gemcitabine chemotherapy was initiated. After six courses of chemotherapy, enhanced computed tomography showed that the mass in the neck of the gallbladder had shrunk to 30 mm, Endoscopic retrograde cholangiopancreatography showed improvement of the hilar duct stenosis. A biopsy of the bile duct mucosa showed no malignant cells in the branch of the left and right hepatic ducts, the left hepatic duct, or the intrapancreatic ducts. The patient underwent conversion surgery with right and segment 4a liver resection, extrahepatic duct resection, and cholangiojejunostomy. The histopathologic diagnosis showed that the tumor cells had shrunk to 2 × 1 mm, and that R0 resection of the T2aN0M0 stage IIA tumor was successful.

Conclusion
Although conversion surgery for gallbladder cancer is rarely possible, curative resection may offer a better prognosis, and it is important to regularly pursue possibilities for surgical resection even during chemotherapy.
Development and validation of a headspace GC-MS method to evaluate the interconversion of impurities and the product quality of liquid hand sanitizers
Authors: Abrigo Nicolas , Ruzicka Connie , Faustino Patrick , Stiber Neil , NguyenPho Agnes , O’Connor Thomas , Shakleya Diaa 
Published: January 2022

AbstractThe COVID-19 pandemic has led to increased usage of hand sanitizer products by the public to prevent the spread of COVID-19 and decrease the likelihood of acquiring the disease. The increase in demand has also led to an increase in the number of manufacturers. This work describes the FDA’s Center for Drug Evaluation and Research (CDER) laboratories efforts to develop tests to assess the quality of hand sanitizer products containing ethanol or isopropanol as the primary active ingredient. The products were evaluated for the active ingredient content and determination of the 12 impurities listed in the FDA Hand Sanitizer Temporary Guidance, followed by a spike recovery assay performed to verify the test results. Extensive method development was conducted including an investigation into the stability of ethanol, isopropanol, and the 12 impurities. Stability and kinetic studies confirmed the instability of acetal in acidic liquid hand sanitizer products during spike recovery assay testing. The headspace GC-MS method was validated according to ICH Q2 (R1) guidelines and the spike recovery assay was validated using three concentrations of standards for the drug product. During method application, six liquid hand sanitizer products were tested and all were determined to have ethanol or isopropanol above 70% v/v. Two liquid hand sanitizer products were determined to contain acetaldehyde as an impurity above the FDA recommended safety levels.
3D printing of nanocomposite pills through desktop vat photopolymerization (stereolithography) for drug delivery reasons
Authors: Sharma Peeyush Kumar , Choudhury Dinesh , Yadav Vivek , Murty U. S. N. , Banerjee Subham 
Published: January 2022

Abstract
Background
The desktop vat polymerization process or stereolithography printing is an ideal approach to develop multifunctional nanocomposites wherein a conventional solid dosage form is used as a reservoir for compliant administration of drug-loaded nanocarriers.

Methods
In this study, a nanocomposite drug delivery system, that is, hydrogel nanoparticles of an approved nutraceutical, berberine entrapped within vat photopolymerized monoliths, was developed for drug delivery applications. For the fabrication of the nanocomposite drug delivery systems/pills, a biocompatible vat photopolymerized resin was selected as an optimum matrix capable of efficiently delivering berberine from stereolithography mediated 3D printed nanocomposite pill.

Results
The obtained data reflected the efficient formation of berberine-loaded hydrogel nanoparticles with a mean particle diameter of 95.05 ± 4.50 nm but low loading. Stereolithography-assisted fabrication of monoliths was achieved with high fidelity (in agreement with computer-aided design), and photo-crosslinking was ascertained through Fourier-transform infrared spectroscopy. The hydrogel nanoparticles were entrapped within the pills during the stereolithography process, as evidenced by electron microscopy. The nanocomposite pills showed a higher swelling in an acidic environment and consequently faster berberine release of 50.39 ± 3.44% after 4 h. The overall results suggested maximal release within the gastrointestinal transit duration and excretion of the exhausted pills.

Conclusions
We intended to demonstrate the feasibility of making 3D printed nanocomposite pills achieved through the desktop vat polymerization process for drug delivery applications.
Judging the credibility of websites: an effectiveness trial of the spacing effect in the elementary classroom
Authors: Foot-Seymour Vanessa , Wiseheart Melody 
Published: January 2022

AbstractSpaced learning—the spacing effect—is a cognitive phenomenon whereby memory for to-be-learned material is better when a fixed amount of study time is spread across multiple learning sessions instead of crammed into a more condensed time period. The spacing effect has been shown to be effective across a wide range of ages and learning materials, but few studies have been conducted that look at whether spacing can be effective in real-world classrooms, using real curriculum content, with real teachers leading the intervention. In the current study, lesson plans for teaching website credibility were distributed to homeroom elementary teachers with specific instructions on how to manipulate the timing of the lessons for either a one-per-day or one-per-week delivery. One month after the final lesson, students were asked to apply their knowledge on a final test, where they evaluated two new websites. Results were mixed, suggesting that classroom noise might lessen or impede researchers’ ability to find spacing effects in naturalistic settings.
Efficient SVV stabilized triangular spectral element methods for incompressible flows of high Reynolds numbers
Authors: Chen Lizhen , Tang Tao , Xu Chuanju 
Published: January 2022

AbstractIn this paper, we propose a spectral vanishing viscosity method for the triangular spectral element computation of high Reynolds number incompressible flows. This can be regarded as an extension of a similar stabilization technique for the standard spectral element method. The difficulty of this extension lies in the fact that a suitable definition of spectral vanishing viscosity operator in non-structured elements does not exist, and it is not clear that if a suitably defined spectral vanishing viscosity provides desirable dissipation for the artificially accumulated energy. The main contribution of the paper includes: 1) a well-defined spectral vanishing viscosity operator is proposed for non-standard spectral element methods for the Navier-Stokes equations based on triangular or tetrahedron partitions; 2) an evaluation technique is introduced to efficiently implement the stabilization term without extra computational cost; 3) the accuracy and efficiency of the proposed method is carefully examined through several numerical examples. Our numerical results show that the proposed method not only preserves the exponential convergence, but also produces improved accuracy when applied to the unsteady Navier-Stokes equations having smooth solutions. Especially, the stabilized triangular spectral element method efficiently stabilizes the simulation of high Reynolds incompressible flows.
MTHFR C677T (rs1801133) genetic polymorphism is associated with development risk of essential hypertension in the Turkish population
Authors: Er Zafer Cengiz , Muderrisoglu Ahmet , Ekim Meral , Ekim Hasan 
Published: January 2022

AbstractBackgroundHypertension is a serious condition that is spread worldwide and may lead to severe complications such as heart attack, stroke, hypertensive retinopathy, and renal failure. Although some genetic and environmental risk factors are known to play a role in the etiology of hypertension, like most of the other multi-factorial diseases, its etiology is yet to be fully elucidated. Our study aimed to investigate the effects of methylenetetrahydrofolate reductase (MTHFR) C677T (rs1801133) and A1298C (rs1801131), factor V Leiden (FVL) G1691A (rs6025), and prothrombin (PT) G20210A (rs1799963) genetic polymorphisms on the development risk of essential hypertension and level of blood pressure in hypertensive patients.ResultsThe frequency of the homozygous polymorphic TT genotype for theMTHFRC677T polymorphism was significantly higher in male hypertensive patients than in the male control group (27% vs 6.3%,p = 0.028). The rate of the variant T allele for theMTHFRC677T polymorphism was also significantly higher in male hypertensive patients compared to male healthy controls (51.4% vs 21.9%,p = 0.0004). There was no difference among hypertensive patients and healthy controls regarding the frequencies ofMTHFRA1298C,FVLG1691A andPTG20210A polymorphisms. In addition, we found no difference between genotype groups regarding systolic and diastolic blood pressure levels in hypertensive patients.ConclusionsHomozygous polymorphic TT genotype and variant T allele for theMTHFRC677T polymorphism may be considered as a risk factor for the development of essential hypertension in the Turkish male population.
Genes linked with early menopause and the pathogenesis of its associated diseases: a systematic review
Authors: Thasneem Kamila , Kalarani Iyshwarya Bhaskar , Jayaprasad Prema , Mohammed Vajagathali , Veerabathiran Ramakrishnan 
Published: January 2022

Abstract
Background
Menopause is a biological process when a woman’s reproductive capability is no longer functional. A naturally or artificially caused premenopausal is known as early menopause occurs between the ages 40–45, which substantially impacts fertility and disease influenced by genetic plus environmental factors and their interactions. Women in early menopause are at greater risk of cardiovascular disease, general mortality, neurological disorders, osteoporosis, mental illness, and other problems.

Main body
A PubMed search of the electronic literature database yielded articles on early menopause and disease etiology. Several unique genes were identified, such as ESR1, ESR2, CYP1B1, BRSK1, HK3, andTMEM150B are associated with early menopause, and research focused on case-control, cohort, and cross-sectional studies are finding novel predisposition loci for early menopause.

Conclusion
The current study’s focus is to understand better the genetic aspects of early menopause. This knowledge will help researchers enhance EM etiology and identify biomarkers that may detect early development of the disease, allowing women at risk to begin family planning earlier.
Study of the effect of vascular endothelial growth factor (VEGF) C(+405)G (rs2010963) single nucleotide polymorphism on the development of esophageal and gastric varices and risk of variceal bleeding in cirrhotic hepatitis C virus (HCV) patients (VEGF) C(+405)G IN esophageal and gastric varices
Authors: Aboismail Ashraf , El-Shazly Mohamed , Abdallah Nasser , Elsayed Eman , Abo-Yossef Rania 
Published: January 2022

AbstractBackgroundHCV infection is a major worldwide cause of chronic liver diseases. Esophageal and gastric varices are common in cirrhotic patients due to concomitant portal hypertension. Variceal hemorrhage is a major decompensating event with high morbidity and mortality. Endothelial dysfunction, occurring in cirrhosis, facilitates the development of liver cirrhosis, portal hypertension and contributes to increased intrahepatic vascular resistance..VEGF family members are major regulators of blood vessel development and function.ResultsThe study was conducted on 90 subjects admitted to Tropical Medicine Department, Alexandria Main University Hospital: 30 cirrhotic patients with endoscopically proven varices (group A), 30 cirrhotic patients without varices (group B), and 30 healthy controls (group C). All patients was subjected to detailed history taking and thorough clinical examination, laboratory investigations, ultrasound abdomen, upper gastrointestinal endoscopy, and genotyping forVEGFC(+405)G (rs2010963) by 5′ nuclease assay. TheVEGFC(+405)G (rs2010963) GG genotype was associated with higher prevalence of esophageal and gastric varices and higher bleeding risk.ConclusionVEGFC(+405)G (rs2010963) is an important genetic determinant of esophageal varices, gastric varices, and correlates with variceal bleeding risk. Genetic testing of this SNP would be useful in prediction of esophageal and gastric varices and bleeding risk.