bluuebunny/crossref_metadata_2025_split huggingface dataset:
BigFiRSt: A Software Program Using Big Data Technique for Mining Simple Sequence Repeats From Large-Scale Sequencing Data
Authors: Chen Jinxiang , Li Fuyi , Wang Miao , Li Junlong , Marquez-Lago Tatiana T. , Leier André , Revote Jerico , Li Shuqin , Liu Quanzhong , Song Jiangning 
Published: January 2022

BackgroundSimple Sequence Repeats (SSRs) are short tandem repeats of nucleotide sequences. It has been shown that SSRs are associated with human diseases and are of medical relevance. Accordingly, a variety of computational methods have been proposed to mine SSRs from genomes. Conventional methods rely on a high-quality complete genome to identify SSRs. However, the sequenced genome often misses several highly repetitive regions. Moreover, many non-model species have no entire genomes. With the recent advances of next-generation sequencing (NGS) techniques, large-scale sequence reads for any species can be rapidly generated using NGS. In this context, a number of methods have been proposed to identify thousands of SSR loci within large amounts of reads for non-model species. While the most commonly used NGS platforms (e.g., Illumina platform) on the market generally provide short paired-end reads, merging overlapping paired-end reads has become a common way prior to the identification of SSR loci. This has posed a big data analysis challenge for traditional stand-alone tools to merge short read pairs and identify SSRs from large-scale data.ResultsIn this study, we present a new Hadoop-based software program, termed BigFiRSt, to address this problem using cutting-edge big data technology. BigFiRSt consists of two major modules, BigFLASH and BigPERF, implemented based on two state-of-the-art stand-alone tools, FLASH and PERF, respectively. BigFLASH and BigPERF address the problem of merging short read pairs and mining SSRs in the big data manner, respectively. Comprehensive benchmarking experiments show that BigFiRSt can dramatically reduce the execution times of fast read pairs merging and SSRs mining from very large-scale DNA sequence data.ConclusionsThe excellent performance of BigFiRSt mainly resorts to the Big Data Hadoop technology to merge read pairs and mine SSRs in parallel and distributed computing on clusters. We anticipate BigFiRSt will be a valuable tool in the coming biological Big Data era.
Normal Faulting Along the Kythira-Antikythira Strait, Southwest Hellenic Forearc, Greece
Authors: Veliz-Borel Violeta , Mouslopoulou Vasiliki , Nicol Andrew , Begg John , Oncken Onno 
Published: January 2022

Upper-plate normal faults along forearcs often accumulate slip during &gt;Mw 6 earthquakes. Such normal faults traverse the forearc of the Hellenic Subduction System (HSS) in Greece and are the focus of this study. Here, we use detailed field-mapping and analysis of high-resolution Digital Elevation Models (DEMs) to study 42 active normal faults on the islands of Kythira and Antikythira in the Aegean Sea. Onshore fault kinematic data are complemented by seabed bathymetry mapping of ten offshore faults that extend along the Kythira-Antikythira Strait (KAS). We find that normal faults in the KAS have lengths of ∼1–58 km and scarps ranging in height from 1.5 m to 2.8 km, accommodating, during the Quaternary, trench-orthogonal (NE-SW) extension of ∼2.46 ± 1.53 mm/a. Twenty-eight of these faults have ruptured since the Last Glacial Maximum, with their postglacial (16 ± 2 ka) displacement rates (0.19–1.25 mm/a) exceeding their Quaternary (≤0.7–3 Ma) rates (0.03–0.37 mm/a) by more than one order of magnitude. Rate variability, which is more pronounced on short (&lt;8 km) faults, is thought to arise due to temporally clustered paleoearthquakes on individual KAS faults. When displacement accumulation is considered across the entire onshore fault network, rate variability between the two time-intervals examined decreases significantly (2.79 ± 0.41 vs 1.29 ± 0.99 mm/a), a feature that suggests that earthquake clustering in the KAS may occur over ≤16 ka timescales.
Research Progress and Applications of Multivalent, Multispecific and Modified Nanobodies for Disease Treatment
Authors: Wang Jiewen , Kang Guangbo , Yuan Haibin , Cao Xiaocang , Huang He , de Marco Ario 
Published: January 2022

Recombinant antibodies such as nanobodies are progressively demonstrating to be a valid alternative to conventional monoclonal antibodies also for clinical applications. Furthermore, they do not solely represent a substitute for monoclonal antibodies but their unique features allow expanding the applications of biotherapeutics and changes the pattern of disease treatment. Nanobodies possess the double advantage of being small and simple to engineer. This combination has promoted extremely diversified approaches to design nanobody-based constructs suitable for particular applications. Both the format geometry possibilities and the functionalization strategies have been widely explored to provide macromolecules with better efficacy with respect to single nanobodies or their combination. Nanobody multimers and nanobody-derived reagents were developed to image and contrast several cancer diseases and have shown their effectiveness in animal models. Their capacity to block more independent signaling pathways simultaneously is considered a critical advantage to avoid tumor resistance, whereas the mass of these multimeric compounds still remains significantly smaller than that of an IgG, enabling deeper penetration in solid tumors. When applied to CAR-T cell therapy, nanobodies can effectively improve the specificity by targeting multiple epitopes and consequently reduce the side effects. This represents a great potential in treating malignant lymphomas, acute myeloid leukemia, acute lymphoblastic leukemia, multiple myeloma and solid tumors. Apart from cancer treatment, multispecific drugs and imaging reagents built with nanobody blocks have demonstrated their value also for detecting and tackling neurodegenerative, autoimmune, metabolic, and infectious diseases and as antidotes for toxins. In particular, multi-paratopic nanobody-based constructs have been developed recently as drugs for passive immunization against SARS-CoV-2 with the goal of impairing variant survival due to resistance to antibodies targeting single epitopes. Given the enormous research activity in the field, it can be expected that more and more multimeric nanobody molecules will undergo late clinical trials in the next future.Systematic Review Registration
Quantitative Analysis of Retinal Vasculature in Rhegmatogenous Retinal Detachment Based on Ultra-Widefield Fundus Imaging
Authors: Feng Bingkai , Su Wenxin , Chen Qingshan , Gan Run , Wang Mingxuan , Wang Jiantao , Zhang Jiayi , Yan Xiaohe 
Published: January 2022

PurposeTo quantitatively analyze retinal vascular morphological features, such as vascular density, caliber, and tortuosity, in rhegmatogenous retinal detachment (RRD).MethodsA total of 244 patients with RRD and 400 healthy controls (HC) were included. Retinal fundus images were collected using OPTOS PLC Daytona P200T. Retinal images were divided into RRD and non-RRD regions of interest (ROIs). All visible retinal fundus vessels were then extracted mainly based on edge detection within ROI to form the whole-vascular image. Retinal vasculature parameters, such as vascular density, caliber, and tortuosity, were calculated.ResultsFor the absolute density, the mean rank (MR) value of normal controls was significantly higher than that in non-RRD (p &lt; 0.001). A consistent tendency of significant vascular density was increased from non-RRD to RRD (p &lt; 0.001). The average and median diameters of normal controls were both significantly larger than RRD (p &lt; 0.001). The average and median diameters were also appeared significantly thinner in non-RRD. Unweighted and width-inversely-weighted vascular tortuosity in RRD and non-RRD comparison exhibited non-significant differences. All types of tortuosity calculated from HC were significantly larger (p &lt; 0.001) in values compared to RRD. All types of tortuosity values of HC were significantly higher than non-RRD. Compared with non-RRD, RRD was significantly larger in area-weighted, length-weighted, and width-weighted vascular tortuosity.ConclusionsThis study showed that RRD affects both the quantity and morphology of retinal vasculature, such as RRD and non-RRD areas. Smaller average and medium vascular diameters and tortuosity values were found in RRD. However, the absolute vascular density, the average and median diameter, and tortuosity values were also reduced in non-RRD although the retina is still attached. This work indicates that RRD may affect the retinal vasculature beyond the detached retina.
A Simple Weaning Model Based on Interpretable Machine Learning Algorithm for Patients With Sepsis: A Research of MIMIC-IV and eICU Databases
Authors: Liu Wanjun , Tao Gan , Zhang Yijun , Xiao Wenyan , Zhang Jin , Liu Yu , Lu Zongqing , Hua Tianfeng , Yang Min 
Published: January 2022

BackgroundInvasive mechanical ventilation plays an important role in the prognosis of patients with sepsis. However, there are, currently, no tools specifically designed to assess weaning from invasive mechanical ventilation in patients with sepsis. The aim of our study was to develop a practical model to predict weaning in patients with sepsis.MethodsWe extracted patient information from the Medical Information Mart for Intensive Care Database-IV (MIMIC-IV) and the eICU Collaborative Research Database (eICU-CRD). Kaplan–Meier curves were plotted to compare the 28-day mortality between patients who successfully weaned and those who failed to wean. Subsequently, MIMIC-IV was divided into a training set and an internal verification set, and the eICU-CRD was designated as the external verification set. We selected the best model to simplify the internal and external validation sets based on the performance of the model.ResultsA total of 5020 and 7081 sepsis patients with invasive mechanical ventilation in MIMIC-IV and eICU-CRD were included, respectively. After matching, weaning was independently associated with 28-day mortality and length of ICU stay (p &lt; 0.001 and p = 0.002, respectively). After comparison, 35 clinical variables were extracted to build weaning models. XGBoost performed the best discrimination among the models in the internal and external validation sets (AUROC: 0.80 and 0.86, respectively). Finally, a simplified model was developed based on XGBoost, which included only four variables. The simplified model also had good predictive performance (AUROC:0.75 and 0.78 in internal and external validation sets, respectively) and was developed into a web-based tool for further review.ConclusionsWeaning success is independently related to short-term mortality in patients with sepsis. The simplified model based on the XGBoost algorithm provides good predictive performance and great clinical applicablity for weaning, and a web-based tool was developed for better clinical application.
Endoscope-Assisted Retrosigmoid Approach for Vestibular Schwannomas With Intracanalicular Extensions: Facial Nerve Outcomes
Authors: Bi Yunke , Ni Yunjia , Gao Dandan , Zhu Qingwei , Zhou Qiangyi , Tang Junjia , Liu Juan , Shi Fei , Li Hongchan , Yin Jian , Liu Yaohua , Lou Meiqing 
Published: January 2022

ObjectiveTo explore the role of neuroendoscope assistance during surgical resection of the intracanalicular portion of vestibular schwannomas via the retrosigmoid approach and the subsequent early facial nerve outcomes.MethodsPatients of vestibular schwannoma with intracanalicular extensions undergoing retrosigmoid dissection at a single institution were retrospectively analyzed in this study. Several surgical techniques were applied to ensure maximal and safe removal of tumors. Tumors extending less than 10 mm into the internal acoustic canal (IAC) were classified as Grade A, while those extending over 10 mm into IAC were taken as Grade B. Neuroendoscope was applied at the end of microscopic phase to search for potential remnants for Grade B tumors. Absolute tumor extension was defined and measured. House and Brackmann (HB) scale was used to evaluate immediate CN VII outcomes.ResultsOf the 61 patients, there were 38 females and 23 males. A total of 18 (29.51%) cases were Koos Grade II, 12 (19.67%) cases Koos Grade III, and 31 (50.82%) cases Koos Grade IV. There were 38 cases (62.30%) of Grade A and 23 cases (37.70%) of Grade B. Gross total resection was achieved in 60 cases (98.36%). Four cases of intracanalicular remnants were detected and completely removed under endoscopic visualizations. There was a significantly higher proportion (17%, p = 0.02) of intracanalicular remnants in Grade B than Grade A. CN VII and VIII were anatomically preserved in all cases. A total of 55 cases (90.16%) retained good (HB Grades 1 and 2) facial nerve outcomes.ConclusionsIn Grade B vestibular schwannomas, after maximal microsurgical removal, endoscopic evaluation of the intracanalicular portion revealed residual tumors in 17% of the patients. Hence endoscopic evaluation of the potential intracanalicular remnants for tumor extending over 10 mm within IAC (Grade B) is recommended.
Overexpression of PD-L1 is an Independent Predictor for Recurrence in HCC Patients Who Receive Sorafenib Treatment After Surgical Resection
Authors: Tan Yifei , Xu Qing , Wu Zhenru , Zhang Wei , Li Bo , Zhang Bohan , Xu Xi , Zhang Bo , Yan Ke , Song Jiulin , Lv Tao , Yang Jian , Jiang Li , Shi Yujun , Yang Jiayin , Yan Lunan 
Published: January 2022

ObjectiveThe predicting values of programmed cell death protein 1 (PD-1) and programmed death-ligand 1(PD-L1) were unclear in Hepatocellular carcinoma (HCC) patients who receive sorafenib treatment after curative hepatic resection.MethodsWe retrospectively enrolled HCC patients who received adjuvant sorafenib treatment after curative resection (N = 154), and patients had resection alone (N = 312). Immunohistochemistry was used to assess expression of PD-1 on tumor infiltration immune cells and PD-L1 on HCC cells. Cox proportional hazard models were used to explore association between clinicopathological factors and risk of tumor recurrence.ResultsNo significant difference was detected in RFS (p = 0.542), or OS (p = 0.542) between the resection and sorafenib group and resection alone group. In the 154 patients who received adjuvant sorafenib, expression of PD-1 or PD-L1 was not significantly associated with long-term outcomes. However, in the 122 patients at high risk of postoperative recurrence who had adjuvant sorafenib treatment, characterized by maxim tumor size ≥5 cm, or the presence of macro- or micro-vascular invasion, patients with PD-L1 overexpression (≥3.0) had significantly worse RFS (p = 0.021), and overexpression of PD-L1 (HR: 1.88, 95%CI: 1.18–2.99, p = 0.008) was identified as an independent risk factor associated with unfavorable RFS.ConclusionOverexpression of PD-L1 serves as an independent predictor of recurrence in HCC patients at high risk of relapse who received adjuvant sorafenib treatment after curative resection.
Efficacy and Safety of Oral Acetaminophen for Premature Infants With Patent Ductus Arteriosus: A Meta-Analysis
Authors: Zi-Yun Xie , Ruo-lin Zhang , Yue-wei Xia , Tao Bo 
Published: January 2022

Objective: To systematically review the efficacy and safety of oral Acetaminophen for premature infants with patent ductus arteriosus (PDA).Methods: Databases including Ovid, EMbase, Pubmed, The Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINHAL), China National Knowledge Infrastructure (CNKI), Chinese Biomedical Database (CBM), WanFang Data, China Science and Technology Journal Database were searched to collect the randomized controlled trials (RCTs) about Acetaminophen for premature infants with PDA from inception to January 1, 2021. Quality assessment was performed through bias risk evaluation according to the Cochrane Handbook 5.1.0, and then the homogeneous studies were analyzed using Revman 5.4 software.Results: A total of 16 RCTs were included, which were divided into for four subgroups: subgroup I (oral acetaminophen vs. oral ibuprofen, 13 RCTs), subgroup II (oral acetaminophen vs. intravenous indomethacin, 1 RCT), subgroup III (oral acetaminophen vs intravenous ibuprofen, 1 RCT), and subgroup IV (oral acetaminophen vs intravenous placebo, 1 RCT). In subgroup I, There was no significant difference in the ductal closure rate after the first course of drug administration [typical relative risk (RR) 0.97, 95% confidence interval (CI) 0.90 to 1.05], the accumulated ductal closure rate after two course of treatment (RR 0.96, 95% CI 0.91–1.02), and mortality (RR 1.06, 95% CI 0.75–1.49) between treatment with oral acetaminophen versus oral ibuprofen (p &gt; 0.05); compared with oral ibuprofen, oral acetaminophen was associated with a significant reduction in the incidence of gastrointestinal bleeding/stool occult blood positive (RR 0.51, 95% CI 0.32 to 0.82)and oliguria (RR 0.62, 95% CI 0.42–0.91) (p &lt; 0.05).Conclusion: The meta analysis approves the facts that there is no significant difference in the efficacity in premature infants with PDA between oral acetaminophen and buprofen or indometacin, but compared to ibuprofen, oral acetaminophen may decrease the incidence of oliguria and gastrointestinal bleeding. More reliable conclusions should be made through large-size, multi-center, well-designed RCTs.
Cilostazol Ameliorates Peripheral Neuropathic Pain in Streptozotocin-Induced Type I Diabetic Rats
Authors: Cheng Kuang-I. , Wang Hung-Chen , Tseng Kuang-Yi , Wang Yi-Hsuan , Chang Chung-Yu , Chen Yi-Jing , Lai Chung-Sheng , Chen Dar-Ren , Chang Lin-Li 
Published: January 2022

Background: Cilostazol is an antiplatelet agent with vasodilating, endothelial function restoration, and anti-inflammatory effects. This study aims to investigate the efficacy of oral cilostazol for preventing the development of diabetic peripheral neuropathy (DPN).Materials and Methods: Ninety adult male Sprague-Dawley rats were divided into five groups: 1) naïve (control); 2) diabetic (DM); 3) DM receiving 10 mg/kg cilostazol (cilo-10); 4) DM receiving 30 mg/kg cilostazol (cilo-30); and 5) DM receiving 100 mg/kg cilostazol (cilo-100). Hindpaw responses to thermal and mechanical stimuli were measured. Activation of microglia and astrocytes in the spinal dorsal horn (SDH) and expression of NaVs in the dorsal root ganglia (DRG) were examined with Western blots and immunofluorescence.Results: DM rats displayed decreased withdrawal thresholds to mechanical stimuli (mechanical allodynia) and blunted responses to thermal stimuli. In addition, the expression of microglia increased, but astrocytes were reduced in the SDH. Upregulation of Nav −1.1, 1.2, −1.3, −1.6, and −1.7 and downregulation of Nav-1.8 were observed in the DRG. The DM rats receiving cilostazol all returned DM-induced decrease in withdrawal threshold to mechanical stimuli and attenuated neuropathic pain. Additionally, all cilostazol treatments suppressed the level of activated microglial cells and ameliorated the DM-induced decline in astrocyte expression levels in the SDH. However, only the rats treated with cilo-100 demonstrated significant improvements to the aberrant NaV expression in the DRG.Conclusion: Oral cilostazol can blunt the responses of mechanical allodynia and has the potential to treat diabetic neuropathy by attenuating NaV and glial cell dysregulation.
Son or Daughter Care in Relation to Self-Reported Health Outcomes for Older Adults in China
Authors: Zhang Yanan , Harper Sarah 
Published: January 2022

ObjectivesParental care in China is traditionally provided by sons. In recent decades—partly due to the One-Child Policy but also economic development and urbanization—significant changes have occurred with more and more parents receiving care from daughters. We investigate the disparities in outcomes of eldercare provided by son(s) and daughter(s).MethodsOur study compares the self-reported health (SRH) status of parents who receive eldercare from daughters and sons in China, analyzing the harmonized 2013, 2015, and 2018 waves of CHARLS with random-effects logistic estimates.ResultsOur results show that the SRH status of parents who receive care from their sons is greater than those cared for by their daughters. This disparity is greater in rural areas, for mothers, and poorer families.DiscussionThe One-Child Policy was more effective in urban areas, reducing both the availability of sons and cultural son preference. Higher levels of education received by girls in urban settings increases their employability and thus their ability to materially care for their parents. However, traditional norms and gender differences in social economic statuses still persist in rural areas, leading to higher SRH status of those cared for by sons, especially amongst those who are heavily dependent on their children: mothers or parents with less wealth.
Cardiac Patch Transplantation Instruments for Robotic Minimally Invasive Cardiac Surgery: Initial Proof-of-concept Designs and Surgery in a Porcine Cadaver
Authors: Roche Christopher D. , Iyer Gautam R. , Nguyen Minh H. , Mabroora Sohaima , Dome Anthony , Sakr Kareem , Pawar Rohan , Lee Vincent , Wilson Christopher C. , Gentile Carmine 
Published: January 2022

Background: Damaged cardiac tissues could potentially be regenerated by transplanting bioengineered cardiac patches to the heart surface. To be fully paradigm-shifting, such patches may need to be transplanted using minimally invasive robotic cardiac surgery (not only traditional open surgery). Here, we present novel robotic designs, initial prototyping and a new surgical operation for instruments to transplant patches via robotic minimally invasive heart surgery.Methods: Robotic surgical instruments and automated control systems were designed, tested with simulation software and prototyped. Surgical proof-of-concept testing was performed on a pig cadaver.Results: Three robotic instrument designs were developed. The first (called “Claw” for the claw-like patch holder at the tip) operates on a rack and pinion mechanism. The second design (“Shell-Beak”) uses adjustable folding plates and rods with a bevel gear mechanism. The third (“HeartStamp”) utilizes a stamp platform protruding through an adjustable ring. For the HeartStamp, rods run through a cylindrical structure designed to fit a uniportal Video-Assisted Thorascopic Surgery (VATS) surgical port. Designed to work with or without a sterile sheath, the patch is pushed out by the stamp platform as it protrudes. Two instrument robotic control systems were designed, simulated in silico and one of these underwent early ‘sizing and learning’ prototyping as a proof-of-concept. To reflect real surgical conditions, surgery was run “live” and reported exactly (as-it-happened). We successfully picked up, transferred and released a patch onto the heart using the HeartStamp in a pig cadaver model.Conclusion: These world-first designs, early prototypes and a novel surgical operation pave the way for robotic instruments for automated keyhole patch transplantation to the heart. Our novel approach is presented for others to build upon free from restrictions or cost—potentially a significant moment in myocardial regeneration surgery which may open a therapeutic avenue for patients unfit for traditional open surgery.