bluuebunny/crossref_metadata_2025_split huggingface dataset:
MODL-09. Exploring the role of Magmas (mitochondria-associated protein involved in granulocyte-macrophage colony-stimulating factor signal transduction) inhibition as a potential therapeutic intervention in medulloblastoma
Authors: Hoerig Clay , Plant-Fox Ashley , Di Kaijun , Lepe Javi , Douglas Christopher , Lomeli Naomi , Das Bhaskar , Bota Daniela 
Published: June 2022

Abstract
BACKGROUND: Brain tumors are the second most common type of pediatric cancer and the leading cause of all cancer-related deaths in children. Medulloblastoma (MB) is the most common type of malignant pediatric brain tumor and has a five-year overall survival ranging from 40-75%, depending on the patient’s age and other prognostic features. There are various anti-cancer therapies against medulloblastoma, but the treatment of recurrent and refractory disease remains a challenge. As a result, the need for new and novel therapies remain a top priority. One area of interest in CNS tumors are targets within mitochondria. Magmas overexpression has been reported in multiple types of metabolically active tissue and cancer cells, including prostate cancer, pituitary adenoma, and glioma. Some new data suggest that specific subgroups of medulloblastoma may also overexpress Magmas. This ongoing study aims to examine whether Magmas inhibition by compound “BT9” could be beneficial in the treatment of medulloblastoma. METHODS: We continue to study the ability of a Magmas inhibitor (BT#9) as a therapeutic agent in stable medulloblastoma cell lines and patient-derived primary cultures by performing MTT assays, tunnel assays, flow cytometry, migration assays, and invasion assays. RESULTS: Similar to the adult GBM studies, Magmas inhibition by BT#9 had signiﬁcant cytotoxic eﬀects, causing both decreased cell proliferation, increased apoptosis, and blocked cell migration in medulloblastoma cell lines DAOY, D283, and D425. IC50s determined for each during different time points demonstrated an average range 2-5μM compared to the average range seen in adult glioblastoma cell cultures which could range up to 10 μM. These findings suggest that the inhibition of Magmas could potentially optimize clinical outcomes in recurrent/refractory medulloblastoma and warrants further investigation. Our future studies will include the determination of IC50s for primary cell cultures and in vitro testing with patient-derived xenograft models.
MODL-19. Exploiting DNA damage response inhibitors to enhance radiation efficacy in medulloblastoma models
Authors: Dholaria Hetal , Buck Jessica , Hii Hilary , Carline Brooke , Bryne Jacob , Kuchibhotla Mani , Lawler Jessica , Porter Gilbert , Whitehouse Jacqueline , Howlett Meegan , Gottardo Nick , Endersby Raelene 
Published: June 2022

Abstract
Despite treatment intensification, survival for certain high-risk subgroups of medulloblastoma (MB) such as p53 mutant SHH (SHHa) and MYC amplified Group 3 (Gr3) have remained dismal. Recently, the use of Carboplatin as radiosensitiser with craniospinal irradiation (CSI) has shown survival benefit in children with Gr3 MB. However, there is an ongoing need to discover newer, non-chemo radiosensitisers which have minimal toxicity and unequivocal benefit in high-risk MB. Radiation is a potent inducer of DNA damage in cancer cells. CHK1/2, ATR, and WEE1 kinases are critical regulators of the DNA damage response (DDR). We hypothesised that inhibition of these kinases may enhance radiation-induced cytotoxicity in MB. We utilised small-animal radiotherapy platform to deliver CSI to MB-tumour-bearing mice that closely mimic clinical settings. Here we demonstrate systematic preclinical evaluation of DDR inhibitors (DDRi) as radiosensitiser in MB models. In vitro treatment of Gr3 MB cell lines with either CHK1/2 inhibitor (CHKi, Prexasertib, AZD7762), ATR inhibitor (ATRi, AZD6738), or WEE1 inhibitor (WEE1i, AZD1775) along with radiation ceased post-radiation cell cycle arrest, prohibiting DNA repair, and increasing apoptosis. The combination also reduced the colony-forming ability of MB cells post-irradiation. In vivo, CSI and DDRi, each induced modest apoptosis in orthotopically-implanted high-risk MB mice. When these models were treated with CHKi+CSI, ATRi+CSI or WEE1i+CSI, the effect was cumulative. Importantly, addition of DDRi to CSI significantly prolonged the survival of MB-bearing mice compared to CSI alone. Here we also explored strategy of “vertical blockade” by simultaneous use of CHKi and WEE1i which when combined with CSI also prolonged survival in MB-bearing mice. Additionally, we evaluated various regimens to best deliver these novel agents with CSI, maximising effect and minimising toxicity. Our study opens up new realms of radiosensitisation with the use of DDRi in paediatric medulloblastoma and provides robust preclinical evidence for clinical translation.
EPEN-21. Developing a sensitive method for detection of minimal residual disease in ependymoma using metabolomic analysis of cerebrospinal fluid
Authors: Woodward Alison , Amugi Laudina , Patel Kishan , Kilpatrick Charlotte , Kim Dong-hyun , Dandapani Madhumita 
Published: June 2022

Abstract
INTRODUCTION: Ependymoma (EPN) is the second most common malignant paediatric brain tumour with poor survival and significant neuro-cognitive impairment from current treatments (surgery and radiotherapy). Relapse occurs in 50% of patients within 2 years, despite no evidence of tumour on MRI. This suggests that they have minimal residual disease (MRD) at the end of treatment. Developing an accurate MRD detection method could help select patients who would benefit from further continuation chemotherapy, thereby improving survival. There is also an unmet need for an accurate test to diagnose relapse early when the disease could be more treatable. METHODS: Pilot untargeted liquid chromatography-mass spectrometry (LC-MS) analysis was carried out in cerebrospinal fluid (CSF) samples from patients with ependymoma. CSF from patients in remission from leukemia were used as controls. RESULTS: Pilot data from analysis of CSF using LC-MS demonstrates that this is a feasible approach to characterise CSF metabolomic profile. Also, EPN CSF profile is significantly different from control CSF, with significant elevation of few key metabolites (Vitamin D derivatives and betaine) in EPN CSF compared to control CSF. Immunohistochemical analysis of EPN tumour tissue microarrays confirms the expression of betaine / one-carbon pathway enzymes such as methionine synthase and betaine—homocysteine S-methyltransferase. Further validation of CSF profile with tumour metabolomic profile and serial CSF sample profiling is currently underway. Subgroup-specific differences and targeted analysis to develop a panel of biomarkers is also being explored. CONCLUSION: Early results suggest that CSF-based metabolite profiling using LC-MS is feasible and could help detect minimal residual disease in ependymoma. Further validation is required to analyse subgroup-specific differences and correlate quantitative changes in metabolites with changing disease burden.
Documenting the Impact Potential of a Menthol Cigarette Ban at Point-of-Sale: A Photograph-Based Analysis of the Presence and Placement of Menthol Versus Regular Cigarette Packs on the Shelves of Tobacco Retail Outlets in New York City
Authors: Kirchner Thomas R , Guttentag Alexandra , Vantu Avigail , Silver Diana 
Published: June 2022

AbstractIntroductionTo investigate the absolute and proportionate number of menthol versus regular cigarette packs displayed on the shelves inside tobacco retail outlets (TROs) across New York City (NYC).Aims and MethodsPhotographic surveillance methods were used to capture the presence and proportionate amount of all visible cigarette packs on the shelves inside N = 160 TROs. Statistical analyses examined the absolute and proportionate number of menthol packs in each TRO as a function of NYC borough, the local TRO environment, population smoking rates derived from the NYC Community Health Survey, and other demographic indicators from the American Community Survey.ResultsThe total number of cigarette packs on the shelves of each TRO and the proportion of menthol packs varied significantly across TROs, averaging about one-quarter of all packs displayed (M = 0.274; SD = .15). Modeling results indicate that the proportion of menthol packs displayed was significantly greater in areas with elevated population smoking rates (odds ratio [OR] = 1.03, CI: 1.01–1.06) and density of TROs per 1000 residents (OR = 1.23; CI: 1.01–1.49), although these associations varied in complex ways with the proportion living under the federal poverty level and the proportion under age 18 years residing within each zip-code.ConclusionsResults of this study demonstrate the utility of photograph-based TRO audit methods for objective, reliable documentation of the presence and proportionate amount of menthol versus other cigarette pack types on TRO shelves and highlight the need to account for sources of variation between small areas when examining the TRO product landscape and evaluating the effectiveness of regulatory actions against menthol.ImplicationsThis study describes use of a “hands-free” surveillance technique that offers valuable advantages over traditional retailer surveillance techniques. Comprehensive photographic surveillance data collection allows for more objective measurements of, in this case, the retail outlet’s tobacco power wall, as multiple coders can review the same images and interrater reliability can be empirically tested. The results of this analysis highlight the need to account for local variation between small areas when examining TRO product landscapes and the effects of policy changes at the retailer level
Reloading DNA History in Rice Domestication
Authors: Izawa Takeshi 
Published: June 2022

AbstractAlthough crop domestication is a prehistoric event, DNA (or genome) sequences of modern cultivars and the accession lines of wild relatives contain information regarding the history of crop domestication and the breeding process. Accordingly, with plentiful genomic data, many new findings have been obtained concerning the crop domestication process, for which various (some controversial) interpretations exist. Since approximately 20 years ago, dozens of quantitative trait genes (QTGs) related to the domestication process have been cloned from several crops including rice, a global staple food. However, the determination of how and when these QTGs were involved in rice domestication requires a precise understanding of the DNA code. In addition to the identification of domestication-related QTGs, large-scale rice genome analysis based on short-read Illumina data (but with shallow depth) including more than 1,000 rice cultivars and hundreds of wild rice (or Oryza rufipogon) lines, along with extensive genome analysis including more than 3,000 cultivars with sufficient Illumina data, has been reported. From these data, the genome-wide changes during rice domestication have been explained. However, these genome-wide changes were not interpreted based on QTG changes for domestication-related traits during rice domestication. In addition, a substantial gap remains between the archeological hypothesis based on ancient relics and findings from DNA variations among current cultivars. Thus, this review reconsiders the present status of rice domestication research from a biologist’s perspective.
Impact of protein supplementation on semen quality, fertility, andBMP1Rgene expression in sheep of Bangladesh
Authors: Khan Md. Kabirul Islam , Hossain Md. Iqbal , Momin Md. Moksedul 
Published: June 2022

AbstractA study was carried out to know the impact of protein supplementation on fertility and expressions of the fertility gene BMP1R. Three International Organization for Standardization (ISO), isocaloric but different levels of protein supplement ration (11.70% crude protein [CP] for control/To, 12.99% CP for T1, and 13.86% CP for T2) were fed to three different groups of sheep. DNA was extracted from the whole blood sample for polymerase chain reaction (PCR) of the BMP1R fertility gene, and purified PCR products were sequenced by a Sanger sequencer. Sequence alignment, pair, and multi-alignment comparison of the BMP1R gene of the species were done with MEGA6. The semen volume (1.0 mL), sperm counts (4.2 × 107 million), and percentage of normal (94.3%) and viable sperm (3.7%) were higher in treatment 2 than in the other two groups. The semen volume (1.0 mL), sperm counts (4.2 × 107 million), and the percentage of normal (94.3%) and viable sperm (3.7%) were higher in treatment 2 than in the other two groups. Ewes treated with supplemented, protein concentrate reached the conception at an earlier age (treatment 1, 9.5 ± 0.16 mo and treatment 2, 10.3 ± 0.04 mo) than control (9.8 ± 0.15 mo). The lambing interval varied, from 198 to 202 d. Lamb’s birth weights in three treated groups were ranging from 1.2 to 1.39 kg. The designated sequences of BMP1R gene revealed 100% homology with the sequence of Kazakh sheep. The present study indicated that the influence of nutrition on reproductive performance and genomic study will be helpful for the genetic improvement of low-productive sheep.
Exporting the Luxembourg Rail Protocol to the Convention on International Interests in Mobile Equipment to Africa
Authors: Otabor-Olubor Iyare 
Published: June 2022

Abstract
This article recommends the Cape Town Convention on International Interests in Mobile Equipment and appeals to African countries to accede to the Luxembourg Protocol on Railway Rolling Stock (Rail Protocol). The discussion in this article focuses on the extent to which Article XXII of the Rail Protocol can be applied with respect to Africa. The article critically analyses the competence of the African Economic Community (AEC) and its sub-regional organizations to accede to the Cape Town Convention and Rail Protocol. The author provides a detailed argumentative analysis of the legal mandate of the AEC and the influence of African Union (AU) laws on the competence of the AEC’s sub-regional organizations to make declarations under the Cape Town Convention and Rail Protocol. The analysis confirms that competence to accede to the Convention and Rail Protocol resides with sovereign States in Africa and not with the AU, the AEC, the Organisation pour l’harmonisation en Afrique du Droit des Affaires, or any existing sub-regional organization in Africa.
An Objective and Easy-to-Use Glaucoma Functional Severity Staging System Based on Artificial Intelligence
Authors: Huang Xiaoqin , Saki Fatemeh , Wang Mengyu , Elze Tobias , Boland Michael V. , Pasquale Louis R. , Johnson Chris A. , Yousefi Siamak 
Published: June 2022

Objective:
The objective of this study was to develop an objective and easy-to-use glaucoma staging system based on visual fields (VFs).

Subjects and Participants:
A total of 13,231 VFs from 8077 subjects were used to develop models and 8024 VFs from 4445 subjects were used to validate models.

Methods:
We developed an unsupervised machine learning model to identify clusters with similar VF values. We annotated the clusters based on their respective mean deviation (MD). We computed optimal MD thresholds that discriminate clusters with the highest accuracy based on Bayes minimum error principle. We evaluated the accuracy of the staging system and validated findings based on an independent validation dataset.

Results:
The unsupervised k-means algorithm discovered 4 clusters with 6784, 4034, 1541, and 872 VFs and average MDs of 0.0 dB (±1.4: SD), −4.8 dB (±1.9), −12.2 dB (±2.9), and −23.0 dB (±3.8), respectively. The supervised Bayes minimum error classifier identified optimal MD thresholds of −2.2, −8.0, and −17.3 dB for discriminating normal eyes and eyes at the early, moderate, and advanced stages of glaucoma. The accuracy of the glaucoma staging system was 94%, based on identified MD thresholds with respect to the initial k-means clusters.

Conclusions:
We discovered that 4 severity levels based on MD thresholds of −2.2, −8.0, and −17.3 dB, provides the optimal number of severity stages based on unsupervised and supervised machine learning. This glaucoma staging system is unbiased, objective, easy-to-use, and consistent, which makes it highly suitable for use in glaucoma research and for day-to-day clinical practice.
Mapping of Perfusion During Full-Thickness Blepharotomy Using Laser Speckle Contrast Imaging
Authors: Wiktorin Anna H. C. , Berggren Johanna V. , Malmsjö Malin , Lindstedt Sandra , Sheikh Rafi , Bohman Elin 
Published: June 2022

Purpose:
The aim of this study was to monitor how the blood perfusion in human upper eyelids is affected during full-thickness blepharotomy.

Methods:
Seven eyelids in 5 patients with upper eyelid retraction due to Graves’ disease underwent full-thickness blepharotomy. Perfusion was measured using laser speckle contrast imaging in the eyelid margin and in the conjunctival pedicle.

Results:
Immediately following the procedure, a nonsignificant reduction in perfusion was observed in the skin of the pretarsal eyelid margin, being 66% of the initial value (p = n.s.). However, a statistically significant decrease in perfusion, to 53% of the initial value (p < 0.01), was seen in the central pedicle of the conjunctiva. There were no surgical complications such as infection, signs of ischemia, or bleeding.

Conclusions:
In this study, eyelid perfusion was mapped during full-thickness blepharotomy for the first time using laser speckle contrast imaging. The results showed that perfusion is sufficiently preserved during surgery, probably due to the rich vascular supply in the periocular region, which may explain the low risk of postoperative complications such as ischemia and infection.
Age-Related Changes in the Lacrimal Punctum Morphology in a Normal Population: Punctum Update (PUP) Study-Paper 1
Authors: Bothra Nandini , Saini Pragya , Ali Mohammad Javed 
Published: June 2022

Purpose:
To define the clinical and optical coherence tomography (OCT) morphology of the lacrimal punctum and assess the age-related changes across 8 decades of life in a normal population.

Methods:
A total of 1310 high-magnification slit-lamp, Fourier-domain OCT (FD-OCT), and optical coherence tomography angiography (OCTA) images were obtained from 320 puncta of normal asymptomatic individuals representing the Indian population. The punctum and peri-punctal area were defined with the help of 2 rims (inner punctal rim and outer punctal rim ) and 3 zones (white zone [Wz], separation zone [Sz], and peri-punctal vascularity). FD-OCT images were used to measure the external punctal diameters and internal lacrimal punctal diameters and the reflectivity patterns of the 3 punctal layers. OCTA was used to assess the branching and extent of vascular networks.

Results:
The upper puncta were narrower and more circular than the lower puncta across the decades. The elevation of the punctal papilla began in the upper puncta in the fifth decade, involved the lower puncta in the sixth decade, and gradually became exaggerated by the eighth decade. A typical punctal narrowing in previously wide puncta began to appear in the sixth decade of life, peaks in the seventh decade, and reverses gradually and spontaneously by the end of the eighth decade of life. The third and fourth decades saw a narrowing of the Sz with prominent vascularity crossing the Sz to reach the Wz. The Sz became indistinct in the fifth and sixth decades of life. The FD-OCT showed gradual thickening and dominance of the fibrous layer from the fifth to eighth decade of life. The clinical vascularity in the peri-punctal region increases from the third decade onwards, with vascular networks becoming increasingly dense, intricate, and branched as the age progresses.

Conclusion:
The present study defined and characterized the involutional changes in a normal population’s first–eighth decades of life. Significant morphological changes were noticed across the different age groups with several clinical implications.
Immunogenicity and Safety of SARS-CoV-2 Vaccination in Patients With Rheumatic Diseases: A Systematic Review and Meta-analysis
Authors: Sood Akhil , Tran Minh , Murthy Vijaya , Gonzalez Emilio 
Published: June 2022

Background
Patients with rheumatic disease (RD) are at increased risk for COVID-19 infection. Large clinical trials have demonstrated efficacy and safety of SARS-CoV-2 vaccine. However, patients with RD are typically excluded from these trials.

Objective
The aim of this study was to conduct a systematic review and meta-analysis examining the immunogenicity and safety of SARS-CoV-2 vaccination in patients with RD.

Methods
We systematically searched PubMed/MEDLINE and Scopus to identify observational studies that examined the immunogenicity and safety of SARS-CoV-2 vaccination in RD patients. Information on disease, immunosuppressant, vaccine type, and proportion of patients with serologic response was obtained from each study.

Results
There were 25 eligible studies. The pooled rate of seroconversion was 0.79 (95% confidence interval [CI], 0.72–0.86). Compared with control subjects, the odds of seroconversion were significantly lower (odds ratio, 0.11; 95% CI, 0.05–0.24). Users of rituximab showed the lowest rate of seroconversion (0.39; 95% CI, 0.29–0.51) followed by mycophenolate (0.56; 95% CI, 0.40–71). On the other hand, users of interleukin 17 (0.94; 95% CI, 0.78–0.98) and tumor necrosis factor inhibitors (0.94; 95% CI, 0.84–0.98) showed high seroconversion rate. Regarding safety of COVID-19 vaccine, approximately 2% of patients reported severe adverse events and 7% reported diseases flares following the first or second dose.

Conclusion
Vaccination against SARS-CoV-2 appears to be safe. Most RD patients developed humoral immune response following vaccination. However, the odds of seroconversion were significantly lower in RD patients compared with controls. This is likely driven by certain immunosuppressants including rituximab and mycophenolate. Future studies need to identify strategies to improve vaccine response in these patients.
One Million and Counting: Estimates of Deaths in the United States from Ancestral SARS-CoV-2 and Variants
Authors: Walker Jo , Grubaugh Nathan D. , Gonsalves Gregg , Pitzer Virginia , Rizvi Zain 
Published: June 2022

AbstractBackgroundOver one million COVID-19 deaths have been recorded in the United States. Sustained global SARS-CoV-2 transmission has led to the emergence of new variants with increased transmissibility, virulence, and/or immune evasion. The specific burden of mortality from each variant over the course of the U.S. COVID-19 epidemic remains unclear.MethodsWe constructed an epidemiologic model using data reported by the CDC on COVID-19 mortality and circulating variant proportions to estimate the number of recorded COVID-19 deaths attributable to each SARS-CoV-2 variant in the U.S. We conducted sensitivity analysis to account for parameter uncertainty.FindingsOf the 1,003,419 COVID-19 deaths recorded as of May 12, 2022, we estimate that 460,124 (46%) were attributable to WHO-designated variants. By U.S. Census Region, the South recorded the most variant deaths per capita (median estimate 158 per 100,000), while the Northeast recorded the fewest (111 per 100,000). Over 40 percent of national COVID-19 deaths were estimated to be caused by the combination of Alpha (median estimate 39,548 deaths), Delta (273,801), and Omicron (117,560).InterpretationSARS-CoV-2 variants that have emerged around the world have imposed a significant mortality burden in the U.S. In addition to national public health strategies, greater efforts are needed to lower the risk of new variants emerging, including through global COVID-19 vaccination, treatment, and outbreak mitigation.