bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of SARS-CoV-2 spike antibody levels among Sputnik V first dose vaccinated people in Pakistan: formulation of national anti-COVID-19 mass vaccination strategy.
Authors: Saeed Umar , Uppal Sara Rizwan , Piracha Zahra Zahid , Khan Aftab Ahmad , Rasheed Azhar , Waheed Amir , Uppal Rehan , Uppal Rizwan 
Published: May 2021

Abstract
Rapid ramp up of immune responses against SARS-CoV-2 during pandemic enables adequate prevention and treatment for COVID-19. Estimating levels of SARS-CoV-2 spike protein antibodies post vaccination is crucial for designing mass-vaccination strategies. The aim of this study was to evaluate effectiveness of Sputnik V first dose in Pakistan. A cross-sectional study of 2000 participants was conducted for examining Gam-COVID-Vac or Sputnik V first dose effects at 21st days post administration at Islamabad Diagnostic Center, Islamabad, Pakistan. From 100 real-time PCR negative (SARS-CoV-2 RNA) individuals, samples were collected and analyzed for antibodies to the SARS-CoV-2 spike protein using Electro-chemiluminescence immunoassay (ECLIA) (Elecsys # 09289267190 Roche, USA). 85% of the participants showed strong positive results with SARS-CoV-2 spike protein antibodies > 1.5 AU/ml. The individuals with antibody titer > 250 AU/ml were 34.9%. Among those with antibody levels > 250 AU/ml 52% had previous history of COVID-19 infection. While participants with > 100 AU/ml of antibodies were 12.7%. However 9.5% showed antibody titer of > 25 AU/ml. 27% of participants had antibody titers of > 1.5–2.5 AU/ml. While antibody titers of < 1.5 AU/ml were observed among 15.9% of participants. Majority of the individuals represented significantly high antibody titers against SARS-CoV-2 even before second booster dose of Ad5 based Sputnik V vaccine. Continuous monitoring of antibody levels among COVID-19 vaccinated populations are deemed to assess humoral immunity status against SARS-CoV-2 infections.
Nomogram to Predict Overall Survival for Gallbladder Cancer Patients With Distant Metastasis
Authors: Wu Mingjie , Zhang Min , Jin Yifeng , Cao Liping 
Published: May 2021

Abstract
Background: There are few studies on the relationship between metastatic sites and prognosis of gallbladder cancer (GBC) patients with distant metastasis. In this study, we aimed to analyze the association between metastatic sites and survival of GBC patients with distant metastasis and developed a nomogram to predict the overall survival (OS).Methods: The information of 1174 GBC patients with distant metastasis was collected from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015, which was based on the 8th edition of TNM staging system. Then patients were divided into a training set and validation set with ratio 7:3. The Cox proportional hazards analysis was performed to find independent prognostic factors and created a nomogram. Concordance index (C-index) and calibration plots were used to validate the predictive accuracy and discriminatory ability of the nomogram, and risk stratification was established based on the nomogram.Results: The Cox proportional hazards analysis showed that the T classification, tumor grade, histology, bone metastasis, liver metastasis, brain metastasis, surgery, and chemotherapy were the independent prognostic factors. The C-index of nomogram in training set and validation set were 0.706 (95%CI [0.686-0.726]) and 0.698 (95%CI [0.665-0.731]), respectively. The calibration plots showed satisfactory accuracy of the nomogram, and patients were divided into three groups base on the nomogram. There were significant differences in survival time between groups.Conclusions: Patients with brain metastasis, liver metastasis, bone metastasis have a poor prognosis, and chemotherapy and surgery may improve the patient's prognosis.
How to Get the Optimal Defibrillation Lead Parameters Using Myocardial Perfusion Scintigraphy in Patients With Coronary Artery Disease
Authors: Atabekov Tariel Abdilazimovich , Batalov Roman Efimovich , Sazonova Svetlana Ivanovna , Krivolapov Sergey Nikolaevich , Khlynin Mikhail Sergeevich , Mishkina Anna , Zavadovsky Konstantin Valerievich , Curnis Antonio , Popov Sergey Valentinovich 
Published: May 2021

Abstract
Introduction. The conventional criteria for a defibrillation lead (DL) implantation don’t take into account presence of scar or deep ischemia in the myocardium. This may impair a proper functioning of the DL. We sought to optimize the DL implantation placement using rest myocardial perfusion scintigraphy (MPS), which allow detecting areas of myocardial hypoperfusion (MH). Purpose. To study the influence of MH and scarring, detected by MPS, on the DL parameters in patients with coronary artery disease (CAD).Methods. 69 patients (male - 65, age 64.8±7.7 years) with CAD and indications for ICD implantation were enrolled. Two days before ICD implantation all patients underwent MPS at rest. Then patients were divided in 2 groups. In the 1st group DL was implanted considering MPS results: to the septal position, if the most significant MH were detected in the apical segments, and to the apical position, if MH were in the septal segments. In the 2nd group DL was implanted using the conventional approach without considering MPS results. Clinical 12 months follow-up was performed with ICD interrogation.Results. Patients of both groups were comparable by clinical and scintigraphic parameters. In the same time, in the 1st group pacing threshold was lower (p<0.0001) and ventricle signal amplitude was higher (p<0.0001) comparing with the 2nd group at all control points. Conclusion. The presence of MH detected by MPS in the area of the DL placement worsens its parameters. The results of MPS in patients with CAD can be useful for optimization of DL placement.
GmFULa Improves Soybean Yield by Enhancing Carbon Assimilation without Altering Flowering Time or Maturity
Authors: Yue Yanlei , Sun Shi , Li Jiawen , Yu Haidong , Wu Hongxia , Sun Baiquan , Li Tao , Han Tianfu , Jiang Bingjun 
Published: May 2021

Abstract
Soybean is highly demanded by a continuously growing human population. However, increasing soybean yield is a major challenge. FRUITFULL ( FUL ), a MADS-box transcription factor, plays important roles in multiple developmental processes, especially fruit and pod development, which are crucial for soybean yield formation. However, the functions of its homologs in soybean are not clear. Here, through haplotypes analysis, we found that haplotypes H02 of the soybean homolog GmFULa ( GmFULa-H02 ) is dominant in cultivated soybeans, suggesting that GmFULa-H02 was highly selected during domestication and varietal improvement of soybean. Interestingly, transgenic overexpression of GmFULa enhanced vegetative growth with more biomass accumulated and ultimately increased the yield but without affecting the plant height or changing the flowering time and maturity, indicating that it enhances the efficiency of dry matter accumulation. It also promoted the yield factors like branch number, pod number and 100-seed weight, which ultimately increased the yield. It increased the palisade tissue cell number and the chlorophyll content to promote photosynthesis and increase the soluble sugar content in leaves and fresh seeds. Furthermore, GmFULa were found to be sublocalized in the nucleus and positively regulate sucrose synthases ( SUSs ) and sucrose transporters ( SUTs ) by binding with the conserved CArG boxes in their promoters. Overall, these results showed GmFULa promotes the capacity of assimilation and the transport of the resultant assimilates to increase yield, and provided insights into the link between GmFULa and sucrose synthesis with transport related molecular pathways that control seed yield.
Exploring the ATR-CHK1 Pathway in the Response of Doxorubicin-induced DNA Damages in Acute Lymphoblastic Leukemia Cells
Authors: Rorà Andrea Ghelli Luserna di , Ghetti Martina , Ledda Lorenzo , Ferrari Anna , Bocconcelli Matteo , Padella Antonella , Napolitano Roberta , Fontana Maria Chiara , Liverani Chiara , Imbrogno Enrica , Bochicchio Maria Teresa , Paganelli Matteo , Robustelli Valentina , Sanogo Seydou , Cerchione Claudio , Fumagalli Monica , Rondoni Michela , Imovilli Annalisa , Musuraca Gerardo , Martinelli Giovanni , Simonetti Giorgia 
Published: May 2021

Abstract
Doxorubicin (Dox) is one of the most commonly used anthracyclines for the treatment of solid and hematological tumors such as B-/T-cell acute lymphoblastic leukemia (ALL). Dox compromises topoisomerase-II enzyme functionality, thus inducing structural damages during DNA replication and causes direct damages intercalating into DNA double helix. Eukaryotic cells respond to DNA damages by activating the ATM-CHK2 and/or ATR-CHK1 pathway, whose function is to regulate cell cycle progression, to promote damage repair and to control apoptosis. We evaluated the efficacy of a new drug schedule combining Dox and specific ATR (VE-821) or CHK1 (prexasertib, PX) inhibitors in the treatment of human B-/T- cell precursor ALL cell lines and primary ALL leukemic cells. We found that ALL cell lines respond to Dox activating the G2/M cell cycle checkpoint. Exposure of Dox-pretreated ALL cell lines to VE-821 or PX enhanced Dox cytotoxic effect. This phenomenon was associated with the abrogation of the G2/M cell cycle checkpoint with changes in the expression pCDK1 and cyclin B1, and cell entry in mitosis, followed by the induction of apoptosis. Indeed, the inhibition of the G2/M checkpoint led to a significant increment of normal and aberrant mitotic cells, including those showing tripolar spindles, metaphases with lagging chromosomes and massive chromosomes fragmentation. In conclusion, we found that the ATR-CHK1 pathway is involved in the response to Dox-induced DNA damages and we demonstrated that our new in vitro drug schedule that combines Dox followed by ATR/CHK1 inhibitors can increase Dox cytotoxicity against ALL cells, while using lower drug doses.
Homozygous R136S mutation in PRNP gene causes recessive inherited early onset prion disease
Authors: Ximelis Teresa , Marín-Moreno Alba , Espinosa Juan Carlos , Eraña Hasier , Charco Jorge M , Hernández Isabel , Riveira Carmen , Alcolea Daniel , González-Roca Eva , Aldecoa Iban , Molina-Porcel Laura , Parchi Piero , Rossi Marcello , Castilla Joaquín , Ruiz-García Raquel , Gelpi Ellen , Torres Juan María , Sanchez-Valle Raquel 
Published: May 2021

Abstract
Background: More than 40 pathogenic heterozygous PRNP mutations causing inherited prion diseases have been identified to date. Recessive inherited prion disease has not been described to date. Methods: We describe the clinical and neuropathological data of inherited early-onset prion disease caused by the rare PRNP homozygous mutation R136S. In vitro PrP Sc propagation studies were performed using recombinant-adapted Protein Mysfolding Cyclic Amplification technique. Brain material from two R136S homozygous patients were intracranially inoculated in TgMet129 and TgVal129 transgenic mice to assess the transmissibility of this rare inherited form of prion disease. Results: The index case presented symptoms of early-onset dementia beginning at the age of 49 and died at the age of 53. Neuropathological evaluation of the proband revealed abundant multicentric PrP plaques and Western blotting revealed a 6-8 kDa protease-resistant, unglycosylated PrP fragment, consistent with a Gerstmann-Sträussler-Scheinker phenotype. Her youngest sibling suffered from progressive cognitive decline, motor impairment and myoclonus with onset in her late 30s and died at the age of 48. Genetic analysis revealed the presence of the R136S mutation in homozygosis in the two affected subjects linked to homozygous methionine at codon 129. One sibling carrying the heterozygous R136S mutation, linked to homozygous methionine at codon 129, is still asymptomatic at the age of 74. The inoculation of human brain homogenates from our index case and an independent case from a Portuguese family with the same mutation in transgenic mice expressing human PrP and in vitro propagation of PrP Sc studies failed to show disease transmissibility. Conclusion: In conclusion, biallelic R136S substitution is a rare variant that produces inherited early-onset human prion disease with a Gerstmann-Sträussler-Scheinker neuropathological and molecular signature. Even if the R136S variant is predicted to be “probably damaging”, heterozygous carriers are protected, at least from an early onset providing the first evidence for a recessive pattern of inheritance in human prion diseases.
Isolation of viable Babesia bovis merozoites to study parasite invasion
Authors: Hakimi Hassan , Asada Masahito , Ishizaki Takahiro , Kawazu Shinichiro 
Published: May 2021

Abstract
Babesia parasite invades exclusively red blood cell (RBC) in mammalian host and induce alterations to host cell for survival. Despite the importance of Babesia in livestock industry and emerging cases in humans, their basic biology is hampered by lack of suitable biological tools. In this study, we aimed to develop a synchronization method for Babesia bovis which causes the most pathogenic form of bovine babesiosis. Initially, we used compound 2 (C2), a specific inhibitor of cyclic GMP-dependent protein kinase (PKG) and a derivative of C2, ML10. While both inhibitors were able to prevent B. bovis egress from RBC and increased percentage of binary forms, removal of inhibitors from culture did not result in a synchronized egress of parasites. Because using PKG inhibitors alone was not efficient to induce a synchronized culture, we isolated viable and invasive B. bovis merozoites and showed dynamics of merozoite invasion and development in RBCs. Using isolated merozoites we showed that BbVEAP, VESA1-export associated protein, is essential for parasite development in the RBC while has no role in invasion. Given the importance of invasion for establishment of infection, this study paves the way for finding novel antigens to be used in control strategies against bovine babesiosis.
Cumulative viral load, an indicator of virulence, is controlled by the host's immune response.
Authors: Iwasa Yoh , Hara Akane , Ozone Shihomi 
Published: May 2021

Abstract
A viral strain may infect a host, proliferate rapidly, become controlled by immune reactions, and eventually be eliminated from the body. The virulence, or the magnitude of harm to the host due to infection, depends on the abundance and duration of the viral strain in the body, and the importance of the damaged tissue of the host. In this study, we investigated how the cumulative viral load (time-integral of the number of infected cells) depends on various factors, such as the viral growth rate, the effectiveness of immune cells to kill infected cells, speed of immune activation, formation of memory cells, and longevity of immune cells. In addition, viruses may produce a mutant with different antigen types, escape the immune reaction targeting the original type, and inflate virulence. We derived four simple formulas for the cumulative viral load that holds in different parameter regions. We analyzed the sensitivity of the cumulative viral load to the parameters in the model. Additionally, we discussed the reported correlation between virulence and molecular evolution rate. We conclude that viral virulence can be mitigated by enhancing the speed and effectiveness of immune reactions and by reducing the viral growth rate.
Recurrent dammed-lake outburst superfloods in the Yigong river, southeastern margin of the Tibet
Authors: Hu Kaiheng , Wu Chaohua , Wei Li , Zhang Xiaopeng , Zhang Qiyuan , Liu Weiming , Yanites Brian J. 
Published: May 2021

Abstract
Landslide dam outburst floods have a significant impact on landform evolution in high mountainous areas. Historic landslide dams on Yigong River, southeastern Tibet, generated two outburst superfloods of > 105 m3/s in 1902 and 2000 AD. One of the slackwater deposits, newly found immediately downstream of historic dams, has been dated to 7 ka BP. One-dimensional backwater stepwise method gives an estimate of 225,000 m3/s for the peak flow related to the paleo-stage indicator of 7 ka BP. The recurrence of at least three huge landslide dam impoundments and super-outburst floods at the exit of the Yigong lake during the Holocene greatly changes the morphology of the Yigong river. Recent reports of giant landslides elsewhere on the southeastern Tibetan Plateau indicate repeated landslide dams at the same location, which counters the traditional viewpoint that landslide damming is spatially random, unlike glacial damming that persists at the same location. Repeated landslide damming may be a persistent source of outburst floods as well as impede the upstream migration of river knickpoints in the southeastern margin.
Genome Analyses Revealed Genetic Admixture and Selection Signatures in Bos indicus
Authors: Dixit S P , Bhatia A K , Ganguly Indrajit , Singh Sanjeev , Dash Soumya , Sharma Anurodh , Kumar N. Anand , Dang A K , Jayakumar S 
Published: May 2021

Abstract
The genomic diversity and relationship among seven diverse cattle breeds viz. Sahiwal, Tharparkar, Gir, Vechur, Ongole, Kangayam and Hariana were investigated in 132 random samples based on high density SNP array comprising > 777K SNPs. A total of 1993 SNPs (0.25% of the total) having greater power (Fst ≥ 0.20) to differentiate these cattle populations were identified, and utilized to partition genome of each animal into a predefined number of clusters. The structure of these cattle indicated shared ancestry of dairy breeds viz. Gir, Tharparkar and Sahiwal. Most of animals (> 76%) of the different populations under study except Vechur clustered into their own group of animals called breed. Vechur population contained highest rate of admixture, consistent with its crossing with other breeds. Ongole, Kangayam and Hariana shared comparatively less of their genome (≤ 15%) with other breeds. The study indicated that all seven breeds evolved from their independent ancestry but there was intermixing of these breeds in the recent past. The selection signatures identified between draft (Kangayam) and dairy breeds included several genes like FAM19A2, RAB31P, BEST3, DGKA, AHCY, PIGU and PFKP which are involved in immune response, metabolic pathway, transportation of glucose and sugars, signaling pathways, cellular processes, cell division and glycolysis regulation, respectively. Moreover, these genomic regions also harbour QTLs affecting milk performance traits. The signatures were also identified even between the dairy breeds. There were also significant differences in number of QTLs affecting production (body weight, growth rate etc.) and morphological traits (height etc.) of short stature, Vechur, compared to large sized cattle. The HMGA2 gene was present in the selection signature on chromosome 5, which may explain the differences in stature of these cattle.
Investigating the histological and structural properties of tendon gel as an artificial biomaterial using the film model method in rabbits
Authors: Shimozaki Kengo , Nakase Junsuke , Ohashi Yoshinori , Kuzumaki Toru , Yamaguchi Tatsuya , Torigoe Kojun , Tsuchiya Hiroyuki 
Published: May 2021

Abstract
Tendon gel, a substance formed during intrinsic tendon regeneration using the film model method, could be a promising artificial biomaterial for revolutionizing tendon healing treatments. Using a rabbit model, this study aimed to detect the properties of tendon gel by investigating the histological and structural differences among tendon gels under different preservation periods. Forty mature female rabbits were divided into four groups of ten rabbits. Achilles tendon rupture models were established using the film model method to obtain tendon gels. A tensile stress was applied to the tendon gel to promote maturation. Although the day-3 and -5 tendon gels were histologically more immature than the day-10 and -15 ones prior to the application of tensile stress, type I collagen fibers equivalent to those of normal tendons were observed in all groups after the tensile process. According to surface and molecular structural evaluations, day-3 tendon gels following tensile process were molecularly cross-linked, and thick collagen fibers similar to those present in normal tendons were observed. Structural maturation observed in day-3 tendon gels caused by traction was hardly observed in day-5, -10, and -15 tendon gels. Hence, the day-3 tendon gel was considered as a novel biomaterial with the best regenerative potential.
Clinical Outcomes and Prognostic Factors of Fractionated Stereotactic Radiation Therapy for Large Brain Metastases as a Potential Alternative to Surgery
Authors: Ogawa Hiroaki , Ito Kei , Karasawa Katsuyuki 
Published: May 2021

Abstract
Introduction: We investigated the outcomes and prognostic factors for fractionated stereotactic radiation therapy (FSRT) for large brain metastases and evaluated whether FSRT could negate the need for surgery, which is the mainstream treatment for large brain metastases.Methods: Patients with brain metastases measuring ≥2 cm treated with FSRT were retrospectively examined. Patients undergoing FSRT postoperatively were excluded. Local failure, intracranial failure, and adverse events were evaluated.Results: Overall, 106 lesions in 98 patients were evaluated. Performance status was 0–1, 2–4, and unknown in 79, 25, and 2 patients, respectively. The median maximum tumor diameter was 25 mm, and the median prescription dose was 35 Gy in 3 fractions. The median follow-up period after FSRT was 7 months. The 1-year rates of local failure, intracranial failure, and overall survival were 13.0%, 57.8%, and 48.0%, respectively. In multivariate analysis, the maximum dose for target ≥135 Gy (biological equivalent dose of a/b of 10 Gy) and good performance status were independent positive prognostic factors for local failure. Sixteen patients (16.3%) were treated with whole-brain radiotherapy after FSRT owing to multiple intracranial recurrences, while surgery was performed for three patients (3.1%) owing to local recurrence.Conclusions: FSRT for large brain metastases achieved good local control and only 3% of patients needed surgery after FSRT, suggesting that FSRT is a potential alternative to surgery. In FSRT, a higher maximum tumor dose was useful for local control.