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Co-infection by Cryptococcus neoformans fungaemia and Non tuberculous Mycobacterium t...
Eihab Subahi
safwan aljafar

Eihab Subahi

and 4 more

February 24, 2021
Opportunistic infections are common in human immunodeficiency virus (HIV)-infected patients. Co-infections with Cryptococcus neoformans together with Mycobacterium and Pneumocystis jiroveci pneumonia (PCP) are rare, and typically occur in immunocompromised individuals, particularly AIDS patients.
Friedreich ataxia in a family from Mali, West Africa
Cheick Abdel Kader Cissé
Lassana Cissé

Cheick Abdel Kader Cissé

and 16 more

February 24, 2021
Friedreich ataxia is the most common inherited ataxia in the world, but yet to be reported in black African. We report the first genetically confirmed case in a West African family. Studying genetic diseases in populations with diverse backgrounds may give new insights into their pathophysiology for future therapeutic targets.
Impact of a formula combining local impedance and conventional parameters on lesion s...
Masateru Takigawa
Masahiko Goya

Masateru Takigawa

and 15 more

February 23, 2021
Background: Although ablation energy (AE) and force-time integral (FTI) are well-known active predictors of lesion characteristics, these parameters do not reflect passive tissue reactions during ablation, which may instead be represented by drops in local impedance (LI). This study aimed to investigate if additional LI-data improves predicting lesion characteristics and steam-pops. Methods: RF applications at a range of powers (30W, 40W, and 50W), contact forces (8g, 15g, 25g, and 35g), and durations (10-180s) using perpendicular/parallel catheter orientations, were performed in excised porcine hearts (N=30). The correlation between AE, FTI and lesion characteristics was examined and the impact of LI (%LI-drop [%LID] defined by the ΔLI/Initial LI) was additionally assessed. Results: 375 lesions without steam-pops were examined. Ablation energy (W*s) and FTI (g*s) showed a positive correlation with lesion depth (ρ=0.824:P<0.0001 and ρ=0.708:P<0.0001), surface area (ρ=0.507:P<0.0001 and ρ=0.562:P<0.0001) and volume (ρ=0.807:P<0.0001 and ρ=0.685:P<0.0001). %LID also showed positive correlation individually with lesion depth (ρ=0.643:P<0.0001), surface area (ρ=0.547:P<0.0001) and volume (ρ=0.733, P<0.0001). However, the combined indices of AE*%LID and FTI*%LID provided significantly stronger correlation with lesion depth (ρ=0.834:P<0.0001 and ρ=0.809P<0.0001), surface area (ρ=0.529:P<0.0001 and ρ=0.656:P<0.0001) and volume (ρ=0.864:P<0.0001 and ρ=0.838:P<0.0001). This tendency was observed regardless of the catheter placement (parallel/perpendicular). AE (P=0.02) and %LID (P=0.002) independently remained as significant predictors to predict steam-pops (N=27). However, the AE*%LID did not increase the predictive power of steam-pops compared to the AE alone. Conclusion: LI, when combined with conventional parameters (AE and FTI), may provide stronger correlation with lesion characteristics.
Adverse events associated with weekly short course isoniazid and rifapentine therapy...
Gabrielle Peck
Mary Staat

Gabrielle Peck

and 6 more

February 23, 2021
Background: Effective yet safe treatment of latent tuberculosis is important for preventing the spread of tuberculosis and the progression to active disease in pediatric patients. As of 2017, the short course combination regimen of weekly isoniazid and rifapentine (3HP) administered by directly observed therapy (DOT) has replaced 9 months of isoniazid as the standard of treatment for latent tuberculosis in pediatric patients. The literature, limited in size, has established the 3HP regimen’s superior safety and adherence. Methods: We completed a retrospective chart review (n = 22) of pediatric patients at our institution receiving this regimen between 2017 and 2019. Frequencies of selected outcomes were compared to data collected in a literature review. Results: In this retrospective chart review, pediatric patients ages 2 to 20 years receiving 3HP with DOT for latent tuberculosis experienced higher adverse event rates, more severe adverse events, and higher treatment discontinuation than that which has been previously reported in the literature. A possible explanation for this finding is that our cohort’s race/ethnicity differed from the cohorts used in the literature. Conclusions: Our data suggests that the short course combination regimen for pediatric latent tuberculosis patients may have a higher adverse event rate than previously established. Although this sample size is small, this study urges further investigation of more diverse cohorts to better establish the regimen’s safety and tolerability.
Health effects of exposure to chlorination by-products in swimming pools: Position Pa...
Mariana Couto
Alfred Bernard

Mariana Couto

and 10 more

February 23, 2021
Concerns have been raised regarding the potential negative effects on human health of water disinfectants used in swimming-pools. Among the disinfection options, the approaches using chlorine-based products have been typically preferred. Chlorine readily reacts with natural organic matter that are introduced in the water mainly through the bathers, leading to the formation of potentially harmful chlorination by-products (CBPs). The formation of CBPs is of particular concern since they have been epidemiologically associated with the development of various clinical manifestations. The higher the concentration of these volatile CBPs in the water, the higher their concentration in the air above the pool, and different routes of exposure to chemicals in swimming-pools (water ingestion, skin absorption and inhalation) contribute to the individual exposome. CBPs may affect the respiratory and skin health of those who stay indoor for long periods, such as swimming instructors, pool staff, and competitive swimmers. Whether those who use chlorinated-pools as customers, particularly children, may also be affected has been a matter of debate. In this article, the EAACI Joint Task Force of the Working Group of Allergy, Asthma & Sports and the Interest Groupf of Environmental & Occupational Allergy discusses the current evidence regarding the health effects of both acute and chronic exposures in different populations (work-related exposures, intensive sports and recreational attendance) and identify the main recommendations and unmet needs for research in this area.
Genomic data shed light on sex-determination in Australian freshwater Percichthyid fi...
Alexandra Pavlova
Katherine Harrisson

Alexandra Pavlova

and 7 more

February 23, 2021
Understanding sex-specific biology can aid conservation management. But understanding genomic sex differences of monomorphic fish species and developing molecular sexing assays is challenged by their diverse sex-determination systems. To facilitate research on Percichthyid fish, predominant in the Australian freshwater biota, we report whole genome sequences and annotations of the endangered Macquarie perch Macquaria australasica and its sister species, the golden perch M. ambigua. To identify sex-linked loci, we conducted whole genome resequencing on 100 known-sex Macquarie perch. In-silico pool-seq comparisons revealed few sex differences, but a 275-Kb SOX-containing scaffold was enriched for gametologous loci- homozygous in females, heterozygous in males. Within this scaffold we reconstructed X- and Y-linked 146-bp haplotypes containing 5 sex-linked SNPs, ~38 Kb upstream of SOX, and developed a PCR-RFLP sexing assay targeting the Y-linked allele of one SNP. We tested this assay in a panel of known-sex Macquarie perch, and smaller panels of three other confamilial species. Amplicon sequencing of 400 bp encompassing the 146-bp region revealed that the few sex-linked positions differ interspecifically, and within Macquarie perch such that its sexing test approached 100% reliability only for the populations used in assay development. Similarly, Macquarie- and golden perch genome-wide DArTseq SNPs revealed different sex-linked loci across non-homologous scaffolds. Overall, we identified 22 sex-linked SNPs in Macquarie perch in a predominantly XX/XY system in which females are homozygous at all 22, and males are heterozygous at 2 or more. The resources here will facilitate multi-locus sexing assays for both species and research on Percichthyid biology.
Tricuspid valve regurgitation management with valve replacement Late Presentation of...
Hong Seok Lee
Tasneem Naqvi

Hong Seok Lee

and 1 more

February 23, 2021
A 51-year-old unrestrained female driver with history of a high-speed motor vehicle accident had been followed due to progressively worsening tricuspid valve regurgitation (TR). Three dimensional (3D0 transesophageal echocardiogram (TEE) showed a TR jet through a perforation in the an avulsed anterior leaflet from the tricuspid valve and another central tricuspid TR jet regurgitation due to tricuspid leafletresulted from malcoaptation of the leaflets from tricuspid annulus annular dilatation.
GC-MS Analysis and Antimicrobial Activity of Essential Oil from (Cymbopogon citratus)...

February 23, 2021
A document by Atheer Khashan. Click on the document to view its contents.
Meta-decision in healthcare
Latifa Baynouna AlKetbi

Latifa Baynouna AlKetbi

February 23, 2021
Meta-decision as a junction between evidence and its rightful implementation is suggested in this review as a structured framework applied in healthcare, valuable to clinicians and healthcare decision-makers. The process of meta-decision requires optimum measurements to provide data necessary for identifying and developing decision alternatives and explicitly reflect on its value and choose the optimum decision. The location of value in the meta-decision framework is core component. Of equal importance are prerequisites for decision-makers' abilities to make meta-decisions and focus on optimum team environments. As well as improving their decision-making process through reflection and learning.
The Innovation-Remuneration Index (IRI). Making pharmaceutical companies report what...
Adam Cohen
Rebecca Ultee

Adam Cohen

and 2 more

February 23, 2021
There is a lack of transparency about the cost of innovation of the pharmaceutical industry even though these costs are claimed to be the major driver for high prices for medicines. This is reflected by annual reports of the major pharmaceutical firms that contain a low number of pages on innovation and its detailed costs, in comparison to pages about remuneration of executives where the detail is excessive. The Innovation/Remuneration Index (IRI) provides an objective view of the transparency priorities of a company and has the potential to shift this focus in favour of transparent and detailed information on the cost of innovation.
Pancreatoblastoma in children: EXPeRT/PARTNER diagnostic and therapeutic recommendati...
Ewa Bien
Jelena Roganovic

Ewa Bien

and 19 more

February 23, 2021
Pancreatoblastoma (PBL) is a rare malignant epithelial neoplasm affecting typically young children. Signs related to advanced upper-abdominal tumor accompanied by elevated serum α-fetoprotein levels in a young child suggest PBL, however histopathological examination is required for diagnosis. The mainstay of treatment is a complete surgical resection. Inoperable and/or metastatic PBL may become amenable to complete, delayed surgery after neo-adjuvant chemotherapy. This manuscript presents the internationally consensus recommendations for the diagnosis and treatment of children with PBL, established by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) within the EU-funded PARTNER (Paediatric Rare Tumors Network – European Registry) project.
Which immunosuppressive drug is preferred in the treatment of toxic epidermal necroly...
Saeedeh  Farajzadeh
Najmeh Ahramiyanpour

Saeedeh Farajzadeh

and 1 more

February 23, 2021
Toxic epidermal necrolysis (TEN) is a serious drug reaction. Its proper cure would be challenging during COVID-19 outbreak because of a dilemma regarding selecting the immunosuppressive drug. In this case presentation, we report a case of TEN who treat successfully with cyclosporine during COVID-19 outbreak in a referral COVID-19 hospital.
PURE NEURITIC LEPROSY PRESENTING WITH TYPE 1 REACTION: A RARE CASE REPORT
Raksha Pathak
Sudha Agrawal

Raksha Pathak

and 2 more

February 23, 2021
Type 1 reaction in pure neuritic leprosy usually occurs in the form of neuritis. Development of new skin lesion during reactional state is rare. The clinicians should be aware about occurrence of Type 1 reaction in pure neuritic leprosy and start timely treatment to prevent further disabilities.
Estimation of microalgal biomass and oil productivity potential in South America by c...
Camila Denise Coronel
LEONARDO CURATTI

Camila Coronel

and 1 more

February 23, 2021
Current production costs of microalgal biomass indicate that only highly-productive cultivation facilities will approach commercial feasibility. Geographical site selection for siting those facilities is critical for achieving target productivities. The aim of this study was to provide a semi-empirical estimation of microalgal biomass and lipids productivity in South America. Simulated-climate was programed in environmental photobioreactors (PhenometricsTM) for a simulation of cultivation in open raceway ponds at different geographical sites. The mean annual South American biomass productivity of 20-cm deep ponds was 12 ± 4 g · m- 2 · d-1. The most productive regions were clustered in the subtropical and tropical regions of the continent. Fortaleza (Brazil) showed a low seasonality and a high annual mean productivity of 23 g · m-2 · d-1 in 5-cm deep ponds. Lipids accumulation and productivity in Fortaleza showed a high microalgal oil accumulation up to 46% (w/w) and a maximum oil productivity of 5 g · m-2 · d-1 for biomass containing around 20% lipids (w/w). This study provides the first semi-empirical estimation of microalgal productivity in South America and supports a high potential of a vast region of the continent.
Molecular basis for higher affinity of SARS-CoV-2 spike RBD for human ACE2 receptor
Julian Delgado
Nalvi Duro

Julian Delgado

and 5 more

February 23, 2021
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused substantially more infections, deaths, and economic disruptions than the 2002-2003 SARS-CoV. The key to understanding SARS-CoV-2’s higher infectivity lies partly in its host receptor recognition mechanism. Experiments show that the human ACE2 protein, which serves as the primary receptor for both CoVs, binds to the receptor binding domain (RBD) of CoV-2’s spike protein stronger than SARS-CoV’s spike RBD. The molecular basis for this difference in binding affinity, however, remains unexplained from X-ray structures. To go beyond insights gained from X-ray structures and investigate the role of thermal fluctuations in structure, we employ all-atom molecular dynamics simulations. Microseconds-long simulations reveal that while CoV and CoV-2 spike-ACE2 interfaces have similar conformational binding modes, CoV-2 spike interacts with ACE2 via a larger combinatorics of polar contacts, and on average, makes 45\% more polar contacts. Correlation analysis and thermodynamic calculations indicate that these differences in the density and dynamics of polar contacts arise from differences in spatial arrangements of interfacial residues, and dynamical coupling between interfacial and non-interfacial residues. These results recommend that ongoing efforts to design spike-ACE2 peptide blockers will benefit from incorporating dynamical information as well as allosteric coupling effects.
Application of fast-track anesthesia in percutaneous transcatheter closure of patent...
Min Li
qing Peng

Min Li

and 1 more

February 23, 2021
Objective : To analyze the application value of fast-track anesthesia in percutaneous occlusion of patent foramen ovale under transesophageal echocardiography. Methodology: 60 cases of patients with patent foramen ovale were randomized into two groups to receive either fast-track anesthesia(Group R) or conventional anesthesia(Group S).Record MAP and HR before anesthesia (T0), tracheal intubation (T1), start of surgery (T2), end of surgery (T3), exit anesthesia recovery room (PACU) (T4), as well as the operation time, anesthesia time , Recovery time of extubation, PACU stay time, recovery period agitation score, pain score VAS out of the anesthesia recovery room (PACU), incidence of adverse reactions. Results: There was no statistically significant difference in the anesthesia time and operation time between the two groups, MAP and HR before and after anesthesia between the two groups were not statistically significant different. There was statistically significant difference in recovery of spontaneous breathing, extubation time, PACU stay time, postoperative restlessness score,and incidence of adverse reactions. Conclusion: Fast-track anesthesia in percutaneous transcatheter closure of patent foramen ovale under transesophageal echocardiography can provide faster recovery of spontaneous breathing, earlier extubation time, shorter PACU stay time, lower postoperative restlessness score, lower incidence of adverse reactions.
Aortic Aneurysm Disease - Make Room for Chronobiology
Aleksandra Lopuszko
Cian Tan

Aleksandra Lopuszko

and 3 more

February 23, 2021
Background Aortic Aneurysm (AA) is a common atherosclerotic condition, accounting for nearly 6,000 deaths in England and up to 175,000 deaths globally each year. The pathological outward bulging of the aorta typically results from atherosclerosis or hereditary connective tissue disorders. AAs are usually asymptomatic until spontaneous rupture or detected on incidental screening. 8 in 10 patients do not survive the rupture and die either before reaching hospital or from complications following surgery. Similar to other cardiovascular pathologies (CVPs), AA is thought to be subject to chronobiological patterns of varying incidence. Methods We performed a literature review of the current literature to evaluate the association between circadian rhythms, seasonal variations, and genetic factors and the pathogenesis of AA, reviewing the impact of chronobiology. Results The incidence of AA is found to peak in the early morning (6 AM – 11 AM) and colder months, and conversely troughs towards the evening and warmer months, exhibiting a similar pattern of chronobiological rhythm as other CVPs such as myocardial infarcts, or cerebrovascular strokes. Conclusion Literature suggests there exists a clear relationship between chronobiology and the incidence and pathogenesis of ruptured AA; incidence increases in the morning (6am - 11am), and during colder months (December – January). This is more pronounced in patients with Marfan Syndrome, or vitamin D deficiency. The underlying pathophysiology and implications this has for chronotherapeutics, are also discussed. Our review shows a clear need for further research into the chronotherapeutic approach to preventing ruptured AA in the journey towards precision medicine.
Spatial and temporal patterns of fish assemblages in mountain streams of the Ren Rive...
Fei Liu
Pengcheng Lin

Fei Liu

and 3 more

February 23, 2021
The spatial-temporal patterns of fish assemblages in lotic systems can provide useful information in developing effective conservation measures. This study aimed to explore the spatiotemporal changes in fish assemblage and their association with environmental factors in mountain streams of Ren River, southwest China. Filed investigations were conducted at 18 sites during rainy and dry season in 2017. A total of 21 species, belonged to 3 orders, 8 families and 19 genera, were collected. Analysis of similarities (ANOSIM) showed fish assemblages structure varied significantly at the spatial scale, but not at the temporal scale. In low order sites, fish assemblages were mainly dominated by cold water and rheophilic species (e.g. Rhynchocypris oxycephalus, Scaphesthes macrolepis, Metahomaloptera omeiensis and Gnathopogon herzensteini), while those in high order sites were predominated by warm water and eurytopicity or stagnophilic species (e.g. Squalidus argentatus, Hemiculter leucisculus and Zacco platypus). Canonical correspondence analysis (CCA) showed fish assemblages were structured by a combination of large-scale landscape factors (e.g. altitude and C-link) and small-scale habitat features (e.g. channel width, water temperature and depth). Among these factors, landscape factors had the greatest influence on fish assemblage, while local habitat measures played less important roles or just acted in certain season.
The design and optimization of novel elliptic cylindrical TSV and its temperature cha...
Wenbo Guan
Hongliang Lu

Wenbo Guan

and 2 more

February 23, 2021
Through Silicon Via (TSV) technology is a key technology to realize multi-layer chips and its structure model and transmission characteristics have attracted much attention. With the continuous reduction of chip size, higher requirements are put forward for the model and transmission characteristics of TSV. A novel elliptic cylindrical TSV structure model is proposed. The influence of axial length ratio, height, dielectric layer thickness and spacing on the transmission characteristics of TSV are further studied by HFSS software. The results show that the transmission of TSV is facilitated by the decrease of axial length ratio, the decrease of height, the increase of dielectric layer thickness and the increase of TSV spacing. The TSV structural parameter values are optimized by a single variable method. The optimized TSV structure is compared with the original TSV, traditional cylindrical and conical TSV and coaxial TSV. It is concluded that the elliptic cylindrical TSV structure has better transmission performance. The temperature characteristics of the elliptic cylindrical TSV are simulated. It is indicated that the transmission characteristics of the elliptic cylindrical TSV are poor at low frequency and better at high frequency when the temperature rises.
Cutaneous and systemic hyperinflammation drives maculopapular drug exanthema in sever...
yasutaka mitamura
Daniel Schulz

yasutaka mitamura

and 18 more

February 23, 2021
Title:
Causes and Consequences of Telomere Lengthening in a Wild Vertebrate Population
thomas brown
Hannah Dugdale

thomas brown

and 5 more

February 23, 2021
Telomeres have been advocated to be important markers of biological age in evolutionary and ecological studies. Telomeres usually shorten with age, and shortening is frequently associated with environmental stressors and increased subsequent mortality. Telomere lengthening – an apparent increase in telomere length between repeated samples from the same individual – also occurs. However, the exact circumstances, and consequences, of telomere lengthening are poorly understood. Using longitudinal data from the Seychelles warbler (Acrocephalus sechellensis), we tested whether telomere lengthening – which occurs in adults of this species – is associated with specific stressors (reproductive effort, food availability, malarial infection and cooperative breeding) and predicts subsequent survival. In females, telomere shortening was observed under greater stress (i.e. low food availability, malaria infection), while telomere lengthening was observed in females experiencing lower stress (i.e. high food availability, assisted by helpers, without malaria). The telomere dynamics of males were not associated with the key stressors tested. These results indicate that, at least for females, telomere lengthening occurs in circumstances more conducive to self-maintenance. Importantly, both females and males with lengthened telomeres had improved subsequent survival relative to individuals that displayed unchanged, or shortened, telomeres – indicating that telomere lengthening is associated with individual fitness. These results demonstrate that telomere dynamics are bidirectionally responsive to the level of stress that an individual faces, but may poorly reflect the accumulation of stress over the lifetime. This study challenges how we think of telomeres as a marker of biological age.
Cryoballoon ablation of the left atrial posterior wall reduces recurrence of persiste...
Takatoshi Shigeta
Yasuteru Yamauchi

Takatoshi Shigeta

and 9 more

February 23, 2021
Introduction: Detailed clinical outcomes of cryoballoon ablation of the left atrial (LA) posterior wall (LAPW) in patients with non-paroxysmal atrial fibrillation (AF) have not been fully examined. Methods: We analyzed the outcomes of 191 patients with non-paroxysmal AF, of whom 135 underwent cryoballoon ablation of the LAPW including the LA roof in addition to pulmonary vein isolation with a cryoballoon. Results: Complete conduction block at the LA roof was obtained in 97.0% (131/135) of patients and LAPW was isolated in 85.2% (115/135) of patients. Over 372 days (range, 182–450 days) of follow-up, atrial arrhythmia recurrence was observed in 55 (40.7%) patients, and atrial tachycardia (AT) recurrence accounted for 25.5% of cases. The prevalence of LA roof cryoballoon ablation tended to be higher in patients without recurrence than those with (74.3% vs. 61.8%, respectively; p=0.11), especially those with persistent AF recurrence (74.5% vs. 46.2%, p=0.01). Multivariate analysis revealed that cryoballoon ablation of the LA roof was a predictor of freedom from persistent AF recurrence and that it was not associated with AT recurrence. Durable LA roof lesions were confirmed in 18 (72.0%) of 25 patients who underwent redo ablation. Conclusion: Cryoballoon ablation of the LAPW leads to a sufficient acute success rate of complete conduction block and durable lesions of the LA roof without increasing the risk of AT recurrence. The prevalence of persistent AF recurrence decreases after additional cryoballoon ablation of the LAPW in patients with non-paroxysmal AF.
Existence and nonexistence of global solutions for logarithmic hyperbolic equation
Yaojun YE

Yaojun YE

February 23, 2021
In this paper, we study the initial-boundary value problem of a class of degenerate quasilinear hyperbolic equation with logarithmic nonlinearity. By applying Galerkin method and the logarithmic Sobolev inequality, we prove the existence of global weak solutions for this problem. Meanwhile,the global nonexistence of solutions is verified by means of the concavity analysis when the initial energy is positive and appropriately bounded.
Comparative Evaluation of ‘Will Bleed, Papworth, Track and Trust’ Bleeding Risk Score...
engin akgül
Abdulkerim Ozhan

engin akgül

and 1 more

February 23, 2021
Background: One of the most undesired complications after open heart operations is bleeding. In our study, we set ourselves two different goals: examining ‘Papworth, Will-Bleed, Track and Trust’ bleeding scoring systems to determine the most predictive one among diabetic patients undergoing isolated coronary bypass surgery, and determining the variables that should be included in the new scoring systems to be established for this patient group. Methods: The files of 297 diabetic patients who underwent isolated coronary artery bypass operation between 2017-2019 were retrospectively reviewed. Patients who underwent emergency surgery with a beating heart, those with reoperated open hart surgery, those with ticagrelor use, and those who died within the first 24 postoperative hours were excluded from the study. Drainage from the thorax and mediastinal tubes and blood product transfusions to the patients within the first 24 hours were noted and analyzed according to scoring systems. Results: Scoring systems are evaluated based on ‘European Multicenter Study on Coronary Artery Bypass Grafting Bleeding Severity (E-CABG)’. In this study including diabetic patients only, Papworth was better predictive of E-CABG bleeding Grade 2-3. We found that Will-Bleed, Track, Trust, the other scoring systems we examined had discriminatory value in terms of E-CABG bleeding Grade 2-3 in our study group. Among the parameters in the scoring systems, we concluded that gender, preoperative hemoglobin (or hematocrit) value, preoperative platelet count, use of antiplatelets until less than five days prior to the operation, and preoperative creatinine (or eGFR) values should be included in the scoring system we aim to establish in the future, called the “Optimum Risk Score for Bleeding (ORS).” Conclusion: Considering the possible risks of bleeding and blood product transfusion, scoring systems that will provide accurate results for patient blood management will be lifesaving and increase the cost-effectiveness of the treatment.
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