bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vitamin D supplementation is a cost-effective intervention after posterolateral lumbar fusion: a systematic review
Authors: Patel Dhiraj , Lippel Matthew , Lunardini David , Monsey Robert , Ziino Chason 
Published: December 2022

Background:
This study investigated the role of preoperative supplementation of 25(OH)D, a precursor of the active form of vitamin D, as a cost-effective strategy to decrease pseudarthrosis rates and overall healthcare burden after posterolateral fusion (PLF). Previous literature has emphasized the importance of vitamin D in bone health maintenance, spinal health, and outcomes in spinal fusion. Inadequate preoperative 25(OH)D levels may increase pseudarthrosis rates after PLF. Thus, a cost-estimation model was developed to determine the cost-effectiveness of both selective and nonselective 25(OH)D supplementation in PLF.

Methods:
Prevalence and cost data were obtained from published literature through systematic reviews. Cost of serum 25(OH)D assay and supplementation were obtained from public-use data. Mean, lower, and upper bounds of 1-year cost-savings were calculated for both supplementation scenarios.

Results:
Preoperative 25(OH)D screening and subsequent selective 25(OH)D supplementation was calculated to result in a mean cost-savings of $10,978,440 ($9,969,394 to $11,987,485) per 10,000 PLF cases. Nonselective 25(OH)D supplementation of all PLF patients was calculated to result in a mean cost-savings of $11,213,318 ($10,204,272 to $12,222,363) per 10,000 cases. Univariate adjustment projects that selective supplementation is a cost-effective strategy in clinical contexts where revision PLF costs exceed $781.89 and prevalence of 25(OH)D deficiency ≥0.612%. Nonselective supplementation is cost-effective in clinical scenarios where revision PLF cost ≥$198.09 and prevalence of 25(OH)D deficiency ≥0.1645%.

Conclusions:
This cost-predictive model promotes the role of preoperative 25(OH)D supplementation as a cost-effective mechanism to reduce overall healthcare burden after PLF. Nonselective supplementation appears to be more cost-effective than selective supplementation, likely due to the relatively lower cost of 25(OH)D supplementation compared with serum assays.

Level of Evidence:
Level III
Discordance in online commercial ratings of orthopaedic surgeons: a retrospective review of online rating scores
Authors: Romere Chase M. , Shah Romil F. 
Published: December 2022

Background:
Patients use online physician ratings to select an orthopaedic surgeon. The objectives of this paper were to investigate whether ratings are concordant among online review sites rating orthopaedic surgeons and examine physician practice characteristics associated with higher physician ratings.

Methods:
Orthopaedic surgeons in Illinois who accepted Medicare patients in 2015 were included in this study. Physician practice characteristics, demographics, and information regarding their Medicare volume were obtained for each surgeon. Information regarding each surgeon’s average and number of ratings was collected from Yelp, Healthgrades, Google, and Vitals.com. The authors examined concordance between sites by investigating how many physicians were given high ratings on one site (>4/5), but low ratings on another site (<2 .5/5). Finally, a multivariable regression model was developed to investigate the association between physician characteristics and online ratings.

Results:
Two hundred ninety-five orthopaedic surgeons were included in the study sample. The number of reviews per physician varied greatly, with some surgeons having as high as 300 and many having no reviews. Of the physicians reviewed as low-performing on one site, 65.9% were rated as high-performing on another site. Physicians were more likely to have better ratings if they graduated after 1995 (P<0.05) or performed a higher volume of Medicare services (P<0.05). Total number of reviews had a statistically significant positive correlation with average rating (r=0.26, P<0.001).

Conclusions:
The discordance among review sites for orthopaedic surgeons suggests that patients should exercise caution when using online reviews. As their use increases, the healthcare community should take a closer look at standardizing reviews.

Level of Evidence:
Level III
Comparison of MRI and bolster hyperextension radiography in determining the flexibility of thoracic curves in Scheuermann kyphosis: a retrospective cross-sectional study
Authors: Chehrassan Mohammadreza , Shakeri Mohammadreza , Nikouei Farshad , Toulany Mahtab , Faraji Mitra , Habibollahzadeh Ali , Ghandhari Hasan 
Published: December 2022

Background:
The flexibility of the thoracic curve is important for the preoperative planning for patients with Scheuermann kyphosis (SK), and a lateral bolster hyperextension radiograph (HE) is the standard available method for this purpose. In this study, the authors aimed to evaluate how the flexibility of the thoracic curve in classic SK patients correlates between supine MRI and HE radiography.

Methods:
In a retrospective cross-sectional study, 38 SK patients who underwent surgical correction were included. Cobb angles were measured on three different images: lateral standing radiographs (EOS), lateral supine bolster HE radiography, and T2-weighted sagittal MRI. The mean differences between the Cobb angles measured on standing radiographs (EOS) and supine modalities (HE and MRI) was considered as the flexibility of the thoracic curve. Measurements were done two times by two orthopaedic spine surgeons, and acceptable intraobserver and interobserver reliability was observed using an intraclass correlation coefficient test.

Results:
The study population included 23 (60.5%) male patients and 15 (39.5%) female patients with a mean age of 23.4±8.8 yr (range 13 to 48). The mean flexibility of the thoracic curve was 31±10.9 degrees (40.5%) on supine MRIs and 36.1±11.5 degrees (47.25%) on bolster HE radiographs. A significant correlation was observed between the mean flexibility of the thoracic curve on MRI and HE radiographs (r=0.601, P<0.001).

Conclusions:
Supine MRI can be regarded as a promising alternative to bolster HE radiography in determining the flexibility of thoracic curves in patients with classic SK.

Level of Evidence:
Level III
Efficacy of acupuncture for chronic prostatitis/chronic pelvic pain syndromes on quality of life: study protocol for a randomized, sham acupuncture-controlled trial
Authors: Ding Yu-Long , Wang Huai-Yu , Ji Yuan , Zhang Shuo , Yuan Peng-Fei , Zhao Hong-Chao , Guo Yan , Xie Xiao-Di 
Published: December 2022

AbstractBackgroundChronic prostatitis/chronic pelvic pain syndromes (CP/CPPS) is a common heterogeneous disease that seriously impacts patients’ quality of life (QoL). Acupuncture therapy has been widely used in China for various urinary diseases and symptoms, including chronic prostatitis. The results of several randomized controlled studies from different countries support that acupuncture can relieve the symptoms of CP/CPPS. Still, most randomized controlled trial (RCT) trials focus on symptom relief in patients, and the evidence on improving the QoL is insufficient. This study aims to assess the near-term and long-term efficacy of acupuncture in improving QoL in patients with CP/CPPS.Methods/DesignThis is a double-arm, parallel, participant-blinded RCT. 70 male CP/CPPS subjects aged 18-50 will be randomly allocated to either the acupuncture group or the sham acupuncture group. Participants will receive acupuncture or sham acupuncture treatment thrice a week over eight weeks for 24 sessions. The primary outcome will be the change in the total score of QoL compared with the baseline after eight weeks of treatment and 24 weeks of follow-up. The expectancy of acupuncture, blinding, and safety will also be assessed. A two-sided test will perform all statistical analyses, and ap-value of less than 0.05 will be considered statically significant.DiscussionThis study aims to provide quantitative clinical evidence of acupuncture effectiveness and safety in improving the QoL in patients with CP/CPPS.Clinical Trial RegistrationThis trial is registered atchictr.org.cn(Identifier: ChiCTR2100051115)
Literature analysis of the efficacy of COVID-19 vaccinations
Authors: Hulsen Tim 
Published: December 2022

AbstractThe COVID-19 pandemic is the largest epidemic of the 21stcentury so far. Over 650 million people have already been infected with the SARS-CoV-2 virus. One of the ways to stop this pandemic, is to vaccinate the population and gain herd immunity. Many different vaccines are being used around the world, with differing efficacy. This review summarizes the 79 publications on the efficacy of the currently existing COVID-19 vaccines. It shows that there are eleven vaccines that have efficacy data published in a PubMed-indexed scientific journal. Most research has been done on the Pfizer/BioNTech BNT162B2 vaccine, and the eleven vaccines generally have a high efficacy in preventing illness. The Pfizer (86%-100%), Moderna (93.2%-94.1%), Sputnik-V (91.6%) and Novavax (∼90%) vaccines show the highest efficacy, followed by the Sinovac (83.5%), QazCovid-in 82%) and Covaxin (77.8%) vaccines. The Oxford/AstraZeneca (69% - 81.5%) and Johnson & Johnson (66%) vaccines have lower efficacy in preventing illness. This overview also shows efficacies other than in preventing illness (e.g. asymptomatic, severe illness, hospitalization, death) in some cases. The results also show that the vaccines have specific effects on specific age groups (e.g. adolescents, adults, elderly) and people with diseases (e.g. leukemia, other cancers, HIV). Future research in this area will mostly focus on vaccine efficacy on specific strains of the SARS-CoV-2 virus (such as the Omicron variant) as well as the efficacy of booster vaccinations.
Omnibus proteome-wide association study (PWAS-O) identified 43 risk genes for Alzheimer’s disease dementia
Authors: Hu Tingyang , Parrish Randy L. , Dai Qile , Buchman Aron S. , Tasaki Shinya , Bennett David A. , Seyfried Nicholas T. , Epstein Michael P. , Yang Jingjing 
Published: December 2022

AbstractProteome-wide association study (PWAS) integrating proteomics data with GWAS data is a powerful tool to identify risk genes for complex diseases, which can inform disease mechanisms with genetic effects mediated through protein abundance. We propose a novel omnibus method to improve PWAS power by modeling unknown genetic architectures with multiple statistical models. We applied TIGAR, PrediXcan, and FUSION to train protein abundance imputation models for 8,430 proteins from dorsolateral prefrontal cortex with whole genome sequencing data (n=355). Next, the trained models were integrated with GWAS summary data of Alzheimer’s disease (AD) dementia (n=762,917) to conduct PWAS. Last, we employed the Aggregated Cauchy Association Test to obtain omnibus PWAS (PWAS-O) p-values from these three models. PWAS-O identified 43 risk genes of AD dementia including 5 novel risk genes that were interconnected through a protein-protein interaction network includingTOMM40,APOC1, andAPOC2. PWAS-O can be easily applied to study complex diseases.
Clinical Virology and Effect of Vaccination and Monoclonal Antibodies against SARS-CoV-2 Omicron Sub Variant BF.7 (BA.5.2.1.7): A systematic review
Authors: Chenchula Santenna , Amerneni Krishna Chaitanya , Ghanta Mohan Krishna , Padmavathi R , Chandra Madhu Bhargavi , Adusumilli Madhu Babu , Mudda Sofia , Chavan Madhavrao , Gupta Rupesh , Lakhawat Bhawna 
Published: December 2022

AbstractSince its identification, the novel coronavirus “severe acute respiratory syndrome coronavirus 2 “(SARS-CoV-2) In in late 2019 AT Wuhan, China, by the World Health Organization (WHO), which cause the coronavirus disease 2019, is rapidly spreading, resulting in the global pandemic. As of 19 December 2022, more than 64 million confirmed cases and 6,645,812 deaths have been reported across the world. Over time, the SARS-CoV-2 acquired genetic mutations resulting in multiple types of SARS-CoV-2 variants and subvariants that have been confirmed. The Omicron (B.1.1.529) variant was identified later in November 2021, with enhanced immune escape and was followed with various sublineages due to mutations in the spike protein of the SARS-CoV-2. However, rapid resurge in COVID-19 reports by Omicron subvariant BF.7(BA.2.75.2) in China and other countries, alarming global threat. The present systematic review was conducted using the MeSH terms and keywords “Omicron” AND “BA.5.2.1.7” OR “BF.7” in Pub Med, Google Scholar and MedRXiv database and grey literature from the authentic database and websites. We identified a total of 14 eligible studies. We have reviewed all the eligible available studies to understand the viral mutations, and factors associated with the increase in the reports of COVID-19 cases in China and across the world and to evaluate the effectiveness of vaccination and monoclonal antibodies against the BF.7 variant.
Revisiting chromatin packaging in mouse sperm
Authors: Yin Qiangzong , Yang Chih-Hsiang , Strelkova Olga S. , Wu Jingyi , Sun Yu , Gopalan Sneha , Yang Liyan , Dekker Job , Fazzio Thomas G. , Li Xin Zhiguo , Gibcus Johan , Rando Oliver J. 
Published: December 2022

ABSTRACTMammalian sperm exhibit an unusual and heavily-compacted genomic packaging state. In addition to its role in organizing the compact and hydrodynamic sperm head, it has been proposed that sperm chromatin architecture helps to program gene expression in the early embryo. Scores of genome-wide surveys in sperm have reported patterns of chromatin accessibility, histone localization, histone modification, and chromosome folding. Here, we revisit these studies in light of recent reports that sperm obtained from the mouse epididymis are contaminated with low levels of cell-free chromatin. In the absence of proper sperm lysis we readily recapitulate multiple prominent genome-wide surveys of sperm chromatin, suggesting that these profiles primarily reflect contaminating cell-free chromatin. Removal of cell-free DNA, along with appropriate lysis conditions, are required to reveal a sperm chromatin state distinct from most previous reports. Using ATAC-Seq to explore relatively accessible genomic loci, we identify a landscape of open loci associated with early development and transcriptional control. Histone modification and chromosome folding studies also strongly support the hypothesis that prior studies suffer from contamination, but technical challenges associated with reliably preserving the architecture of the compacted sperm head prevent us from confidently assaying true localization patterns for these epigenetic marks. Together, our studies strongly argue that our knowledge of mammalian chromosome packaging remains largely incomplete, and motivate future efforts to more accurately characterize genome organization in mature sperm.
RecQ1 helicase unwinds G-Quadruplexes at oriLyt to facilitate KSHV Lytic DNA Replication
Authors: Dabral Prerna , Uppal Timsy , Verma Subhash C. 
Published: December 2022

ABSTRACTKSHV utilizes distinct origins of DNA replication (origin of replications) during the latent and lytic phases of its life cycle. Lytic DNA replication requires the participation of cellular and viral proteins to initiate replication at a specific region in the KSHV genome, oriLyt. These regions contain multiple secondary structures and binding sites for the viral and cellular proteins. We discovered the presence of G-quadruplex (G4s) sites in the oriLyt region. G-quadruplexes are secondary structures in nucleic acid sequences that are considered regulators of multiple biological processes, such as transcription, translation, and replication initiation. Importantly, herpesviruses have a high density of PQS (putative quadruplex formation sites) in their genome, including in the regulatory regions, which control replication and transcription. The binding of RecQ1 to the oriLyt region of KSHV and its ability to unwind the G4 structures led us to speculate that G-quadruplex sites play an important role in lytic DNA replication. In this study, we confirmed the formation of stable G-quadruplexes through biochemical and biophysical assays. We further demonstrated that RecQ1 associates with the G4 sites of the oriLyt. The functional significance of RecQ1-mediated unwinding of G4 sites was confirmed by the inhibition and depletion of RecQ1 activity and protein levels through a pharmacologic inhibitor and short-hairpin, respectively. Furthermore, the detection of replication initiation through single-molecule analysis of the replicated DNA (SMARD) approach demonstrated that G4 stabilization leads to a subdued initiation of replication at the oriLyt. This confirmed the role of the G-quadruplex in regulating viral DNA replication, which can be used for controlling virus growth.SignificanceBiological processes originating from the DNA and RNA can be regulated by the secondary structures present in the stretch of nucleic acids, and the G-quadruplexes are shown to regulate transcription, translation, and replication. In this study, we identified the presence of multiple G-quadruplex sites in the region (oriLyt) of KSHV DNA, which is essential for the replication of DNA during the lytic cycle. We demonstrated the roles of these G-quadruplexes through multiple biochemical and biophysical assays in controlling replication and efficient virus production. We demonstrated that KSHV achieves this by recruiting RecQ1 (helicase) at these G-quadruplex sites for efficient viral DNA replication. Analysis of the replicated DNA through nucleoside labeling and immunostaining showed a reduced initiation of DNA replication in cells with a pharmacologic stabilizer of G-quadruplexes. Overall, this study confirmed the role of the G-quadruplex in regulating viral DNA replication, which can be exploited for controlling viral DNA replication.
Neurotensin receptor allosterism revealed in complex with a biased allosteric modulator
Authors: Krumm Brian E. , DiBerto Jeffrey F. , Olsen Reid H. J. , Kang Hye Jin , Slocum Samuel T. , Zhang Shicheng , Strachan Ryan T. , Slosky Lauren M. , Pinkerton Anthony B. , Barak Lawrence S. , Caron Marc G. , Kenakin Terry , Fay Jonathan F. , Roth Bryan L. 
Published: December 2022

SUMMARYThe NTSR1 neurotensin receptor (NTSR1) is a G protein coupled receptor (GPCR) found in the brain and peripheral tissues with neurotensin (NTS) being its endogenous peptide ligand. In the brain, NTS modulates dopamine neuronal activity, induces opioid-independent analgesia, and regulates food intake. Recent studies indicate that biasing NTSR1 toward β-Arrestin signaling can attenuate the actions of psychostimulants and other drugs of abuse. Here we provide the cryoEM structures of NTSR1 ternary complexes with heterotrimeric Gq and Go with and without the brain penetrant small molecule SBI-553. In functional studies, we discovered that SBI-553 displays complex allosteric actions exemplified by negative allosteric modulation for G proteins that are Gαsubunit selective and positive allosteric modulation and agonism for β-Arrestin translocation at NTSR1. Detailed structural analysis of the allosteric binding site illuminated the structural determinants for biased allosteric modulation of SBI-553 on NTSR1. These insights promise to both accelerate the structure-guided design of more effective NTSR1 therapeutics and provide insights into the complexities of GPCR allosteric modulation.
pomBseen: An Automated Pipeline for Analysis of Fission Yeast Images
Authors: Ohira Makoto , Rhind Nicholas 
Published: December 2022

AbstractpomBseen is a image analysis pipeline for the quantitation of fission yeast micrographs containing a brightfield channel and up to two fluorescent channels. It accepts a wide range of image formats and produces a table with the number, size and total and nuclear fluorescent intensities of the cells in the image. Written in MATLAB, pomBseen is also available as a standalone application.
PAXIP1 and STAG2 converge to maintain 3D genome architecture and facilitate promoter/enhancer contacts to enable stress hormone-dependent transcription
Authors: Mayayo-Peralta Isabel , Gregoricchio Sebastian , Schuurman Karianne , Yavuz Selçuk , Zaalberg Anniek , Kojic Aleksander , Abbott Nina , Geverts Bart , Beerthuijzen Suzanne , Siefert Joseph , Severson Tesa M. , van Baalen Martijn , Hoekman Liesbeth , Lieftink Cor , Altelaar Maarten , Beijersbergen Roderick L. , Houtsmuller Adriaan B. , Prekovic Stefan , Zwart Wilbert 
Published: December 2022

ABSTRACTHow steroid hormone receptors (SHRs) orchestrate transcriptional activity remains only partly understood. Upon activation, SHRs bind the genome and recruit their co-regulators, crucial to induce gene expression. However, it remains unknown which components of the SHR-recruited co-regulator complex are essential to drive transcription following hormonal stimuli. Through a FACS-based genome-wide CRISPR screen, we comprehensively dissected the Glucocorticoid Receptor (GR) co-regulatory complex involved in gene-target regulation. We describe a novel functional cross-talk between PAXIP1 and the cohesin subunit STAG2 that is critical for regulation of gene expression by GR. Without altering the GR cistrome, PAXIP1 and STAG2 depletion alter the GR transcriptome, by impairing the recruitment of 3D-genome organization proteins to the GR complex. Importantly, we demonstrate that PAXIP1 is required for stability of cohesin on the genome, its localization to GR-occupied sites, and maintenance of enhancer-promoter interactions. Moreover, in lung cancer, where GR acts as tumor suppressor, PAXIP1/STAG2 loss enhances GR-mediated tumor suppressor activity by modifying local chromatin interactions. All together, we introduce PAXIP1 and STAG2 as novel co-regulators of GR, required to maintain 3D-genome architecture and drive the GR transcriptional programme following hormonal stimuli.
Cross-link scrambling in peptide pairs
Authors: de Jong Luitzen , Roseboom Winfried , Kramer Gertjan 
Published: December 2022

AbstractIdentification of peptides and their linked amino acids from chemically cross-linked protein complexes with bifunctional N-hydroxysuccinimidyl (NHS) esters can reveal interacting proteins and their spatial arrangements. With NHS esters both amide- and ester cross-links can be formed. Retention time prediction for strong cation exchange chromatography (SCXC) of cross-linked peptides at pH 3 can distinguish between ester and amide cross-links based on their charge differences. By this approach we show that about 98 % of cross-links are formed by two amide bonds. However MS/MS analysis revealed the presence of an ester linkage in more than 5% of peptide pairs predicted by SCXC to be linked by amide bonds. This discrepancy can be explained by intra-peptide amide-ester rearrangement in the gas phase during MS/MS analysis. So, SCXC retention time prediction can be used to distinguish amide-amide, amide-ester and ester-ester linkages actually formed in the cross-linking reaction and to detect scrambling of cross-linked sites. This information is important for studies aimed to understand the spatial arrangement of protein complexes by cross-linking at the highest possible resolution.