bluuebunny/crossref_metadata_2025 huggingface dataset:
PREDICTIVE MAINTENANCE USING LONG SHORT-TERM MEMORY ALGORITHM ON SENSOR DATA
Authors: Shruthika Suma
Published: December 2021

Think of a complex system with very expensive
parts. We can't risk running into failure as it will be
extremely costly to repair highly damaged parts. But
more importantly, it's a safety issue. This is why
numerous organizations attempt to avoid failure
beforehand by performing regular inspections on their
equipment. One big challenge is to determine when to do
maintenance. Since we don't know when failure will
occur, we have to be conservative in our planning. LTSM
can be used to predict the remaining useful life. But if we
schedule maintenance very early, we will end up wasting
machine life that is still usable, and this will add up to
our costs. However, if we can predict when machine
failure will occur, we can schedule maintenance right
before it. Recurrent Neural Networks can predict when
this machine failure is bound to happen. Predictive
maintenance lets us estimate time to failure. It also
pinpoints problems in complex machinery and helps us
identify what parts need to be fixed. This way, we can
minimize downtime and maximize equipment lifetime.
Using Innovation to Develop Digital Tools for Public Health During the COVID-19 Pandemic
Authors: Mark Kate , Bradley Jay , Chute Chaloner , Sumpter Colin , Adil Mahmood , Crooks George
Published: December 2021

Introduction: Technology has played a key role in enabling public health to respond to the COVID-19 pandemic at a pace and scale never seen before. The Digital Health and Care Innovation Centre (DHI) assisted with development of two new digital services to enable testing and contact tracing at scale using innovative methods.

Methods: The DHI employed a design innovation approach by bringing all relevant stakeholders together to co-design new technology services to identify the ‘preferred future’. Workshops were used to identify the preferred solutions. The innovative methods for development of digital health tools included adopting an iterative approach, addressing the situational requirements posed by COVID-19, and democratising technology for purposes of pandemic control.

Results: A National Notification Service (NNS) for automation of delivery and feedback (if results messages were viewed) was developed and adopted by five of the 14 health boards in Scotland, processing over 7 million results since inception.

The Simple Tracing Tools (STT) is an open-platform web-based app that is designed for data entry by contact tracing teams. STT was adopted by all local health protection teams and informed development of the national case management system.

Discussion: The Cynefin framework can be used to understand the design innovation process when facing the challenges of designing digital tools during a pandemic. There are significant opportunities for public health to engage with digital health to transform the pandemic response and derive benefit for tackling future population health challenges.
Pretransplant Determinants of Outcome in Patients with Myeloma Undergoing Autologous Transplantation in Lower Resource Settings
Authors: Nair Chandran K
Published: December 2021

The treatment landscape in multiple myeloma has significantly changed since the introduction of high-dose melphalan with autologous stem cell rescue in the 1980s. Many randomised controlled trials have clearly demonstrated the superiority of autologous stem cell transplantation in improving survival compared to conventional chemotherapy. However, outcomes in myeloma are highly variable with median survival as short as 2 years and as long as 10 years or more. The main adverse factor predicting shorter survival is presence of high-risk cytogenetics. However, there are many other potential factors that can contribute to the treatment outcomes.  This review looks at the various pretransplant variables that are associated with  post-transplant outcomes in myeloma.
Pharmacokinetics of Amoxicillin and Cefepime During Prolonged Intermittent Renal Replacement Therapy: A Case Report
Authors: Xu Jessica H , Cheng Vesa , Rawlins Matthew , Lennon Joanne , Morgan David , McWhinney Brett C , Ungerer Jacobus PJ , Wilde Alice , Dyer John , Roberts Jason A
Published: December 2021

Prolonged intermittent renal replacement therapy (PIRRT) is an emerging form of renal replacement therapy in critically ill patients, but dosing data for antibiotics such as amoxicillin and cefepime are scarce and limited. This case report describes the effect of PIRRT on the plasma pharmacokinetics of amoxicillin and cefepime in a 69-year-old, critically ill patient with a polymicrobial intra-abdominal infection. Blood samples taken over 2 days, including a 7-hour PIRRT session, were analysed and a two-compartment model was used to describe cefepime and amoxicillin clearance and dosing requirements during PIRRT and off-PIRRT in this patient. Based on these data, an off-PIRRT dose of 1 g amoxicillin 12-hourly and cefepime 2 g daily with an on-PIRRT dose of 1 g amoxicillin 8-hourly and cefepime 2 g 12-hourly was deemed appropriate.
The Non-coding MicroRNA-223 is a Promising Biomarker of Chronic Kidney Disease
Authors: Metzinger-Le Meuth Valerie , Metzinger Laurent
Published: December 2021

Renal diseases are consecutive to a deregulation of gene expression regulated by non-coding RNAs. These non-coding RNAs were discovered at the turn of the 21st century when it was established that post-transcriptional regulation was performed through small non-coding RNAs, known as microRNAs (miRNAs). Up to 3,000 miRNAs are expressed by human cells. They are small, single-stranded nucleic acids, which trigger translational repression of mRNA by base-pairing with the 3′ untranslated region of their mRNA targets. In addition to miRNA regulation, it was also demonstrated that 60,000 long non-coding RNAs are expressed in the human cell and that they are able to regulate gene expression at all levels. The roles of these various RNA families are just beginning to be understood in the field of nephrology. In the past decade, the authors and various others have published that several miRNAs are deregulated during the onset of chronic kidney disease (CKD) and are associated with cardiovascular damage. This review focuses on miRNA-223 (miR-223) as its expression is increased in vivo in the large vessels of a mouse model of CKD, whereas it is diminished in the serum of both mice and human patients with CKD. In patients, miR-223 expression was correlated with all-cause mortality, as well as cardiovascular and renal events. Molecular clues were given by a multi-omics approach, indicating that miR-223 modulates gene regulation at all levels including mRNA expression, protein amounts, and metabolic molecule accumulation. miR-223 is thus a potential target to prevent or treat complications of CKD pathogenesis.
Expert-analytical approach to assessing activity of vitamin D based on determination of vitamin D associated links by indicators of water-electrolyte metabolism
Authors: Solomennikov A. V. , Bogdanova S. L. , Tyukavin A. I. , Arsenyev N. A.
Published: December 2021

The authors used the proposed method of mathematical and statistical processing of laboratory data (indicators of electrolyte metabolism and osteomarkers) of archived data of 82 patients with various bone diseases aged 9.90 ± 0.55 years compared the structural changes in the panel of ratios of individual electrolytes and the inﬂuence of individual indicators on them in personalized data, on the basis of which a conclusion was made about a single mechanism of coinciding inﬂuences in the exchange of bone tissue. At the same time, it was found that the complex of associated links detected by the vitamin inﬂuence on the panel of electrolyte ratios may differ signifcantly in some cases from each other. These differences consisted in highly pronounced differences in the activity of vitamin D in relation to various components of osteosynthesis and osteolysis, which are described in the modern literature. On this basis, the authors conclude that the used method (analytical system) allows to identify the functional connections of the dynamics of the indicator of vitamin D in individual cases with the dynamics of other indicators of bone, which signifcantly expands the informativeness of the results of laboratory examination of the patient in determining the leading systems the implementation of functional activity of the vitamin. The presented results justify the possibility of creating and describing different images of vitamin D-related changes in the plasma electrolyte composition, followed by their use in the identifcation of certain disorders of calcium metabolism and/or evaluating the effectiveness of the therapy used in each individual case.
Clinical and laboratory markers of calcifying atherosclerosis
Authors: Drygina L. B. , Khirmanov V. N.
Published: December 2021

Despite the achievements in the detection of calcium deposits in the walls of blood vessels, there is practically no data on the relationship of calcification of the coronary arteries with clinical and laboratory indicators of calcification in the blood, and the mechanisms of this process have not been fully established. The aim of the work was to establish the relationship between the severity of vascular calcification and clinical and laboratory markers of vascular calcification to improve the effectiveness of the diagnosis of diseases of the cardiovascular system and optimize therapy. The data obtained during the study indicate a high prevalence of vascular calcification in patients with atherosclerosis. Estimates of the calcium index and traditional risk factors are not always sufficient to predict cardiovascular complications. Thus, the identification of specific laboratory markers of calcification and predisposition to calcinosis is very relevant at the present time. Studies have shown that atherosclerosis with vascular calcification is combined with the development of chronic systemic inﬂammation and inﬂammation of the vascular wall. At the same time, there are elevated levels of C-reactive protein, endothelin, homocysteine, lipid metabolism indicators, and reduced levels of fetuin-A in the blood, which allows us to recommend these laboratory indicators to prevent cardiovascular complications.
Streptococcus pneumoniae carriage in school children
Authors: Protasova I. N. , Bakhareva N. V. , Ilyenkova N. A. , Sokolovskaya E. S. , Elistratova T. A. , Suldina A. G.
Published: December 2021

Purpose. To investigate the serotype distribution, clonal structure and antimicrobial resistance of pneumococci isolated from schoolchildren.

Materials and methods. During the period from 2012 to 2018 we examined 498 healthy school children aged 6 to 17 years. Oropharyngeal swab was taken from each child for culture, after that all S. pneumoniae strains were genotyped for serotype and ST-type deduction (PCR and sequencing, respectively). Antimicrobial resistance was also determined.

Results. Pneumococcal culture was positive in 10.6 % of children. S. pneumoniae isolates belonged to seven serogroups and seven serotypes. Serogroup 6 and serotype 19F strains (15.1% each), and serogroup 9 strains (13.2%) were the most prevalent. S. pneumoniae33FA/37 and 3 (9.4 and 5.7%), serogroups 15 and 18 (7.6 and 5.7%), and 10A serotype (3.8%) were determined at a lower frequency. 20 detected ST-types belonged to 14 clonal complexes (CCs); CC156, CC447, and CC320 were predominant. 1.9% of isolates were penicillin-resistant; 13.2% – macrolide-, clindamycin-, and tetracycline-resistant. S. pneumoniae antibiotic resistant strains belonged to multidrug-resistant CCs 320, 315, and 156.

Conclusion. S. pneumoniae prevalence in school children is not high. Pneumococcal population is characterized by serotype and clonal diversity including ‘invasive’ serotypes and genotypes. Most of strains are susceptible to antimicrobials.
Orbits Theory. A Complete Proof of the Collatz Conjecture
Authors: Crespo Alvarez Jorge
Published: December 2021

In this work a complete proof of the Collatz Conjecture is presented. The solution assumes as hypothesis that Collatz's Conjecture is a consequence. We found that every natural number n_i∈N can be calculated starting from 1, using the function n_i=((2^(i-Ω)-C))⁄3^Ω , where: i≥0 represents the number of steps (operations of multiplications by two subtractions of one and divisions by three) needed to get from 1 to n_i, Ω≥0 represents the number of multiplications by three required and 0≤C≤2^(i-⌊i/3⌋ )-2^((i mod 3)) 3^⌊i/3⌋ is an accumulative constant that takes into account the order in which the operations of multiplication and division have been performed. Reversing the inversion, we have obtained the function: ((3^Ω n_i+C))⁄2^(i-Ω)=1 that proves that Collatz Conjecture it’s a consequence of the above and also proofs that Collatz Conjecture it’s true since ((3^Ω n_i+C))⁄2^(i-Ω) is the recursive form of the Collatz’s function.
Analysis of Geometric and Hemodynamic Profiles in Rat Arteriovenous Fistula Following PDE5A Inhibition
Authors: Northrup Hannah , Somarathna Maheshika , Corless Savanna , Falzon Isabelle , Totenhagen John , Lee Timmy , Shiu Yan-Ting
Published: December 2021

Arteriovenous fistula (AVF) is essential for chronic kidney disease (CKD) patients on hemodialysis, but treatment for AVF maturation failure remains an unmet clinical need. Successful AVF remodeling occurs through sufficient lumen expansion to increase AVF blood flow and lumen area. Aberrant blood flow is thought to impair AVF remodeling, but previous literature has largely focused on hemodynamics averaged over the entire AVF or at a single location. We hypothesized that hemodynamics is heterogeneous, and thus any treatment’s effect size is heterogeneous in the AVF. To test our hypothesis, we used the PDE5A inhibitor sildenafil to treat AVFs in a rat model and performed magnetic resonance imaging (MRI) based computational fluid dynamics (CFD) to generate a detailed spatial profile of hemodynamics in AVFs. 90 mg/kg of sildenafil was administered to rats in their drinking water for 14 days. On day 14 femoral AVFs were created in rats and sildenafil treatment continued for another 21 days. 21 days post-AVF creation, rats underwent non-contrast MRI for CFD and geometrical analysis. Lumen cross-sectional area (CSA) and flow rate were used to quantify AVF remodeling. Parameters used to describe aberrant blood flow include velocity magnitude, wall shear stress (WSS), oscillatory shear index (OSI), and vorticity. Geometrical parameters include arterial-venous (A-V) distance, anastomosis angle, tortuosity, and nonplanarity angle magnitude. When averaged across the entire AVF, sildenafil treated rats had significantly higher CSA, flow rate, velocity, WSS, OSI, and vorticity than control rats. To analyze heterogeneity, the vein was separated into zones: 0–5, 5–10, 10–15, and 15–20 mm from the anastomosis. In both groups: 1) CSA increased from the 0–5 to 15–20 zone; 2) velocity, WSS, and vorticity were highest in the 0–5 zone and dropped significantly thereafter; and 3) OSI increased at the 5–10 zone and then decreased gradually. Thus, the effect size of sildenafil on AVF remodeling and the relationship between hemodynamics and AVF remodeling depend on location. There was no significant difference between control and sildenafil groups for the other geometric parameters. Rats tolerated sildenafil treatment well, and our results suggest that sildenafil may be a safe and effective therapy for AVF maturation.
Climate Change Impacts on Wind Waves Generated by Major Tropical Cyclones off the Coast of New Jersey, USA
Authors: Marsooli Reza , Jamous Mohammad , Miller Jon K.
Published: December 2021

Coastal areas of State of New Jersey in the Northeastern United States are exposed to extreme wind waves generated by tropical cyclones in the Atlantic Ocean. Past studies suggest that the frequency and intensity of major hurricanes in the Atlantic basin would increase under high greenhouse gas emission scenarios. Furthermore, sea level observations have revealed that the local mean sea level along the coast of New Jersey is rising at a rate higher than that of the global sea level rise. The objective of this study is to quantify the combined influence of sea level rise (SLR) and hurricane climatology change on wave heights induced by major hurricanes off the coast of New Jersey. To this end, a coupled hydrodynamic-wave model is utilized to simulate wind waves for synthetic hurricanes generated for the climate conditions in the historical period of 1980–2000 and future period of 2080–2100 under the RCP8.5 high emission scenario. The synthetic storms are generated by a hurricane model for the climate conditions obtained from four different global climate models. The projections of future wave heights show statistically significant increases in the wave heights induced by major hurricanes. Under the combined effects of hurricane climatology change and a SLR of 1.19 m, the increase in the extreme wave heights 15% in back-bays and shallow waters of the nearshore zone and up to 10% in deeper coastal waters. It is found that SLR alone would result in a significant increase in the hurricane-induced wave heights in the present-day surf zone.
Integration of Transcriptome and Methylome Highlights the Roles of Cell Cycle and Hippo Signaling Pathway in Flatfish Sexual Size Dimorphism
Authors: Wang Na , Yang Qian , Wang Jialin , Shi Rui , Li Ming , Gao Jin , Xu Wenteng , Yang Yingming , Chen Yadong , Chen Songlin
Published: December 2021

Sexual size dimorphism (SSD) is the difference in segments or body size between sexes prevalent in various species. Understanding the genetic architecture of SSD has remained a significant challenge owing to the complexity of growth mechanisms and the sexual influences among species. The Chinese tongue sole (Cynoglossus semilaevis), which exhibits a female-biased SSD and sex reversal from female to pseudomale, is an ideal model for exploring SSD mechanism at the molecular level. The present study aimed to integrate transcriptome and methylome analysis to unravel the genetic and epigenetic changes in female, male, and pseudomaleC. semilaevis. The somatotropic and reproductive tissues (brain, liver, gonad, and muscle) transcriptomes were characterized by RNA-seq technology. Transcriptomic analysis unravelled numerous differentially expressed genes (DEGs) involved in cell growth and death-related pathways. The gonad and muscle methylomes were further employed for screening differentially methylated genes (DMGs). Relatively higher DNA methylation levels were observed in the male and pseudomale individuals. In detail, hypermethylation of the chromosome W was pronounced in the pseudomale group than in the female group. Furthermore, weighted gene co-expression network analysis showed that turquoise and brown modules positively and negatively correlated with the female-biased SSD, respectively. A combined analysis of the module genes and DMGs revealed the female-biased mRNA transcripts and hypomethylated levels in the upstream and downstream regions across the cell cycle-related genes. Moreover, the male and pseudomale-biased gene expression in the hippo signaling pathway were positively correlated with their hypermethylation levels in the gene body. These findings implied that the activation of the cell cycle and the inhibition of the hippo signaling pathway were implicated inC. semilaevisfemale-biased SSD. In addition, the dynamic expression pattern of the epigenetic regulatory factors, includingdnmt1,dnmt3a,dnmt3b, anduhrf1, among the different sexes correspond with their distinct DNA methylation levels. Herein, we provide valuable clues for understanding female-biased SSD inC. semilaevis.
Ovarian Cancer-Driven Mesothelial-to-Mesenchymal Transition is Triggered by the Endothelin-1/β-arr1 Axis
Authors: Del Rio Danila , Masi Ilenia , Caprara Valentina , Spadaro Francesca , Ottavi Flavia , Strippoli Raffaele , Sandoval Pilar , López-Cabrera Manuel , Sainz de la Cuesta Ricardo , Bagnato Anna , Rosanò Laura
Published: December 2021

Transcoelomic spread of serous ovarian cancer (SOC) results from the cooperative interactions between cancer and host components. Tumor-derived factors might allow the conversion of mesothelial cells (MCs) into tumor-associated MCs, providing a favorable environment for SOC cell dissemination. However, factors and molecular mechanisms involved in this process are largely unexplored. Here we investigated the tumor-related endothelin-1 (ET-1) as an inducer of changes in MCs supporting SOC progression. Here, we report a significant production of ET-1 from MCs associated with the expression of its cognate receptors, ETA and ETB, along with the protein β-arrestin1. ET-1 triggers MC proliferation via β-arrestin1-dependent MAPK and NF-kB pathways and increases the release of cancer-related factors. The ETA/ETB receptor activation supports the genetic reprogramming of mesothelial-to-mesenchymal transition (MMT), with upregulation of mesenchymal markers, as fibronectin, α-SMA, N-cadherin and vimentin, NF-kB-dependent Snail transcriptional activity and downregulation of E-cadherin and ZO-1, allowing to enhanced MC migration and invasion, and SOC transmesothelial migration. These effects are impaired by either blockade of ETAR and ETBR or by β-arrestin1 silencing. Notably, in peritoneal metastases both ETAR and ETBR are co-expressed with MMT markers compared to normal control peritoneum. Collectively, our report shows that the ET-1 axis may contribute to the early stage of SOC progression by modulating MC pro-metastatic behaviour via MMT.
Inhibition of the Anti-Apoptotic Bcl-2 Family by BH3 Mimetics Sensitize the Mitochondrial Permeability Transition Pore Through Bax and Bak
Authors: Patel Pooja , Mendoza Arielys , Robichaux Dexter J. , Wang Meng C. , Wehrens Xander H. T. , Karch Jason
Published: December 2021

Mitochondrial permeability transition pore (MPTP)-dependent necrosis contributes to numerous pathologies in the heart, brain, and skeletal muscle. The MPTP is a non-selective pore in the inner mitochondrial membrane that is triggered by high levels of matrix Ca2+, and sustained opening leads to mitochondrial dysfunction. Although the MPTP is defined by an increase in inner mitochondrial membrane permeability, the expression of pro-apoptotic Bcl-2 family members, Bax and Bak localization to the outer mitochondrial membrane is required for MPTP-dependent mitochondrial dysfunction and subsequent necrotic cell death. Contrary to the role of Bax and Bak in apoptosis, which is dependent on their oligomerization, MPTP-dependent necrosis does not require oligomerization as monomeric/inactive forms of Bax and Bak can facilitate mitochondrial dysfunction. However, the relationship between Bax and Bak activation/oligomerization and MPTP sensitization remains to be explored. Here, we use a combination of in vitro and ex vivo approaches to determine the role of the anti-apoptotic Bcl-2 family members, which regulate Bax/Bak activity, in necrotic cell death and MPTP sensitivity. To study the role of each predominantly expressed anti-apoptotic Bcl-2 family member (i.e., Mcl-1, Bcl-2, and Bcl-xL) in MPTP regulation, we utilize various BH3 mimetics that specifically bind to and inhibit each. We determined that the inhibition of each anti-apoptotic Bcl-2 family member lowers mitochondrial calcium retention capacity and sensitizes MPTP opening. Furthermore, the inhibition of each Bcl-2 family member exacerbates both apoptotic and necrotic cell death in vitro in a Bax/Bak-dependent manner. Our findings suggests that mitochondrial Ca2+ retention capacity and MPTP sensitivity is influenced by Bax/Bak activation/oligomerization on the outer mitochondrial membrane, providing further evidence of the crosstalk between the apoptotic and necrotic cell death pathways.
The Interactome in the Evolution From Frailty to Sarcopenic Dependence
Authors: Coto-Montes Ana , González-Blanco Laura , Antuña Eduardo , Menéndez-Valle Iván , Bermejo-Millo Juan Carlos , Caballero Beatriz , Vega-Naredo Ignacio , Potes Yaiza
Published: December 2021

Biomarkers are essential tools for accurate diagnosis and effective prevention, but their validation is a pending challenge that limits their usefulness, even more so with constructs as complex as frailty. Sarcopenia shares multiple mechanisms with frailty which makes it a strong candidate to provide robust frailty biomarkers. Based on this premise, we studied the temporal evolution of cellular interactome in frailty, from independent patients to dependent ones. Overweight is a recognized cause of frailty in aging, so we studied the altered mechanisms in overweight independent elderly and evaluated their aggravation in dependent elderly. This evidence of the evolution of previously altered mechanisms would significantly support their role as real biomarkers of frailty. The results showed a preponderant role of autophagy in interactome control at both different functional points, modulating other essential mechanisms in the cell, such as mitochondrial capacity or oxidative stress. Thus, the overweight provoked in the muscle of the elderly an overload of autophagy that kept cell survival in apparently healthy individuals. This excessive and permanent autophagic effort did not seem to be able to be maintained over time. Indeed, in dependent elderly, the muscle showed a total autophagic inactivity, with devastating effects on the survival of the cell, which showed clear signs of apoptosis, and reduced functional capacity. The frail elderly are in a situation of weakness that is a precursor of dependence that can still be prevented if detection is early. Hence biomarkers are essential in this context.
Cell Lineage Infidelity in PDAC Progression and Therapy Resistance
Authors: Malinova Antonia , Veghini Lisa , Real Francisco X. , Corbo Vincenzo
Published: December 2021

Infidelity to cell fate occurs when differentiated cells lose their original identity and either revert to a more multipotent state or transdifferentiate into a different cell type, either within the same embryonic lineage or in an entirely different one. Whilst in certain circumstances, such as in wound repair, this process is beneficial, it can be hijacked by cancer cells to drive disease initiation and progression. Cell phenotype switching has been shown to also serve as a mechanism of drug resistance in some epithelial cancers. In pancreatic ductal adenocarcinoma (PDAC), the role of lineage infidelity and phenotype switching is still unclear. Two consensus molecular subtypes of PDAC have been proposed that mainly reflect the existence of cell lineages with different degrees of fidelity to pancreatic endodermal precursors. Indeed, the classical subtype of PDAC is characterised by the expression of endodermal lineage specifying transcription factors, while the more aggressive basal-like/squamous subtype is defined by epigenetic downregulation of endodermal genes and alterations in chromatin modifiers. Here, we summarise the current knowledge of mechanisms (genetic and epigenetic) of cell fate switching in PDAC and discuss how pancreatic organoids might help increase our understanding of both cell-intrinsic and cell-extrinsic factors governing lineage infidelity during the distinct phases of PDAC evolution.
Disproportionate Mitral Regurgitation Determines Survival in Acute Heart Failure
Authors: Berrill Max , Beeton Ian , Fluck David , John Isaac , Lazariashvili Otar , Stewart Jack , Ashcroft Eshan , Belsey Jonathan , Sharma Pankaj , Baltabaeva Aigul
Published: December 2021

Objectives: To assess the prevalence and impact of mitral regurgitation (MR) on survival in patients presenting to hospital in acute heart failure (AHF) using traditional echocardiographic assessment alongside more novel indices of proportionality.

Background: It remains unclear if the severity of MR plays a significant role in determining outcomes in AHF. There is also uncertainty as to the clinical relevance of indexing MR to left ventricular volumes. This concept of disproportionality has not been assessed in AHF.

Methods: A total of 418 consecutive patients presenting in AHF over 12 months were recruited and followed up for 2 years. MR was quantitatively assessed within 24 h of recruitment. Standard proximal isovelocity surface area (PISA) and a novel proportionality index of effective regurgitant orifice/left ventricular end-diastolic volume (ERO/LVEDV) >0.14 mm2/ml were used to identify severe and disproportionate MR.

Results: Every patient had MR. About 331/418 (78.9%) patients were quantifiable by PISA. About 165/418 (39.5%) patients displayed significant MR. A larger cohort displayed disproportionate MR defined by either a proportionality index using ERO/LVEDV > 0.14 mm2/ml or regurgitant volumes/LVEDV > 0.2 [217/331 (65.6%) and 222/345 (64.3%), respectively]. The LVEDV was enlarged in significant MR−129.5 ± 58.95 vs. 100.0 ± 49.91 ml in mild, [p < 0.0001], but remained within the normal range. Significant MR was associated with a greater mortality at 2 years {44.2 vs. 34.8% in mild MR [hazard ratio (HR) 1.39; 95% CI: 1.01–1.92, p = 0.04]}, which persisted with adjustment for comorbid conditions (HR; 1.43; 95% CI: 1.04–1.97, p = 0.03). Disproportionate MR defined by ERO/LVEDV >0.14 mm2/ml was also associated with worse outcome [42.4 vs. 28.3% (HR 1.62; 95% CI 1.12–2.34, p = 0.01)].

Conclusions: MR was a universal feature in AHF and determines outcome in significant cases. Furthermore, disproportionate MR, defined either by effective regurgitant orifice (ERO) or volumetrically, is associated with a worse prognosis despite the absence of adverse left ventricular (LV) remodeling. These findings outline the importance of adjusting acute volume overload to LV volumes and call for a review of the current standards of MR assessment.

Clinical Trial Registration:https://clinicaltrials.gov/ct2/show/NCT02728739, identifier NCT02728739.
Valvulo-Arterial Impedance and Dimensionless Index for Risk Stratifying Patients With Severe Aortic Stenosis
Authors: Mantha Yogamaya , Futami Shutaro , Moriyama Shohei , Hieda Michinari
Published: December 2021

The hemodynamic effects of aortic stenosis (AS) consist of increased left ventricular (LV) afterload, reduced myocardial compliance, and increased myocardial workload. The LV in AS patients faces a double load: valvular and arterial loads. As such, the presence of symptoms and occurrence of adverse events in AS should better correlate with calculating the global burden faced by the LV in addition to the transvalvular gradient and aortic valve area (AVA). The valvulo-arterial impedance (Zva) is a useful parameter providing an estimate of the global LV hemodynamic load that results from the summation of the valvular and vascular loads. In addition to calculating the global LV afterload, it is paramount to estimate the stenosis severity accurately. In clinical practice, the management of low-flow low-gradient (LF-LG) severe AS with preserved LV ejection fraction requires careful confirmation of stenosis severity. In addition to the Zva, the dimensionless index (DI) is a very useful parameter to express the size of the effective valvular area as a proportion of the cross-section area of the left ventricular outlet tract velocity-time integral (LVOT-VTI) to that of the aortic valve jet (dimensionless velocity ratio). The DI is calculated by a ratio of the sub-valvular velocity obtained by pulsed-wave Doppler (LVOT-VTI) divided by the maximum velocity obtained by continuous-wave Doppler across the aortic valve (AV-VTI). In contrast to AVA measurement, the DI does not require the calculation of LVOT cross-sectional area, a major cause of erroneous assessment and underestimation of AVA. Hence, among patients with LG severe AS and preserved LV ejection fraction, calculation of DI in routine echocardiographic practice may be useful to identify a subgroup of patients at higher risk of mortality who may derive benefit from aortic valve replacement. This article aims to elucidate the Zva and DI in different clinical situations, correlate with the standard indexes of AS severity, LV geometry, and function, and thus prove to improve risk stratification and clinical decision making in patients with severe AS.
Use of Anti-angiogenic Drugs Potentially Associated With an Increase on Serum AST, LDH, CK, and CK-MB Activities in Patients With Cancer: A Retrospective Study
Authors: Zheng Qi , Wang Hanzhou , Hou Wei , Zhang Ying
Published: December 2021

Background: There is a large amount of evidence that anti-angiogenic drugs are effective safe. However, few studies have evaluated the specific effects of anti-angiogenic drugs on myocardial enzyme injury biomarkers: aspartate aminotransferase (AST), lactic dehydrogenase (LDH), creatine kinase (CK) and creatine kinase isoenzyme (CK-MB). The purpose of our study was to determine whether anti-angiogenic drugs serum AST, LDH, CK, and CK-MB activities of cancer patients treated with anti-angiogenic drugs.

Methods: This study retrospectively analyzed 81 cancer patients. Patients who had used anti-angiogenic drugs were selected. Serum AST, LDH, CK, and CK-MB activities were measured before and after treatment with anti-angiogenic drugs for 3 weeks.

Results: A total of 16 cancer types were analyzed. The distribution of the cancer types in the patients was mainly concentrated in lung, gastric, and colorectal cancers. The anti-angiogenic treatment markedly increased AST, LDH, CK, and CK-MB activities by 32.51, 7.29, 31.25, and 55.56%, respectively in serum.

Conclusions: Our findings suggest that patients, who had used anti-angiogenic drugs were likely to have elevated AST, LDH, and CK, indicators of myocardial muscle injury. Use of anti-angiogenic drugs should not be assumed to be completely safe and without any cardiovascular risks.
Diffusing Capacity for Carbon Monoxide Predicts Response to Balloon Pulmonary Angioplasty in Patients With Inoperable Chronic Thromboembolic Pulmonary Hypertension
Authors: Li Xin , Zhang Yi , Luo Qin , Zhao Qing , Zeng Qixian , Yang Tao , Jin Qi , Yan Lu , Duan Anqi , Liu Jiaran , An Chenhong , Ma Xiuping , Xiong Changming , Zhao Zhihui , Liu Zhihong
Published: December 2021

Background: The hemodynamic results of balloon pulmonary angioplasty vary among patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Previous studies revealed that microvasculopathy accounted for residual pulmonary hypertension after pulmonary endarterectomy, which could be reflected by the diffusing capacity for carbon monoxide (DLCO). We aimed to identify whether the DLCO could predict the BPA response.

Materials and Methods: We retrospectively analyzed 75 consecutive patients with inoperable CTEPH who underwent BPA from May 2018 to January 2021 at Fuwai Hospital. According to the hemodynamics at follow-up after the last BPA, patients were classified as “BPA responders” (defined as a mean pulmonary arterial pressure ≤ 30 mmHg and/or a reduction of pulmonary vascular resistance ≥ 30%) or “BPA nonresponders.”

Results: At the baseline, BPA responders had significantly higher DLCO values than nonresponders, although the other variables were comparable. In BPA responders, the DLCO decreased after the first BPA session and then returned to a level similar to the baseline at follow-up. Conversely, the DLCO increased constantly from the baseline to follow-up in nonresponders. Multivariate logistic analysis showed that a baseline DLCO of <70% and a percent change in DLCO between the baseline and the period within 7 days after the first BPA session (ΔDLCO) of > 6% were both independent predictors of an unfavorable response to BPA. Receiver operator characteristic analysis showed that the combination of a baseline DLCO < 70% and ΔDLCO > 6% demonstrated a better area under the curve than either of these two variables used alone.

Conclusions: A baseline DLCO < 70% and ΔDLCO > 6% could independently predict unfavorable responses to BPA. Measuring the DLCO dynamically facilitates the identification of patients who might have unsatisfactory hemodynamic results after BPA.
The Increase in Paraoxonase 1 Is Associated With Decrease in Left Ventricular Volume in Kidney Transplant Recipients
Authors: Connelly Philip W. , Yan Andrew T. , Nash Michelle M. , Wald Rachel M. , Lok Charmaine , Gunaratnam Lakshman , Kirpalani Anish , Prasad G. V. Ramesh
Published: December 2021

Background: Patients on dialysis have impaired cardiac function, in part due to increased fluid volume and ventricular stress. Restored kidney function through transplantation reduces left ventricular volume in both systole and diastole. We previously reported that the decrease in NT-proB-type natriuretic peptide (NT-proBNP) was associated with a decrease in adiponectin. Paraoxonase 1 (PON1) has been inversely associated with cardiovascular outcomes. We now report the association of changes in PON1 with changes in left ventricular volume and left ventricular mass after kidney transplantation.

Design: Patients on dialysis were assessed at baseline and 12 months after kidney transplantation (n = 38). A comparison group of patients on dialysis who were not expected to receive a transplant in the next 24 months were studied (n = 43) to determine if the change of PON1 with kidney transplantation achieved a significance greater than that due to biologic variation. Left ventricular volume and mass were determined by cardiac magnetic resonance imaging. PON1 was measured by arylesterase activity and by mass.

Results: PON1 mass and activity were not different between the groups at baseline. Both PON1 mass and activity were increased post-kidney transplantation (p < 0.0001 for change). The change in PON1 mass (p = 0.0062) and PON1 arylesterase activity (p = 0.0254) were inversely correlated with the change in NT-proBNP for patients receiving a kidney transplant. However, only the change in the PON1 mass, and not the change in PON1 arylesterase, was inversely correlated with the change in left ventricular volume (ml/m2.7) (p = 0.0146 and 0.0114 for diastolic and systolic, respectively) and with the change in hemoglobin (p = 0.0042).

Conclusion: Both PON1 mass and arylesterase activity are increased by kidney transplantation. The increase in PON1 mass is consistent with a novel relationship to the increase in hemoglobin and decrease in left ventricular volume and NT-proBNP seen when kidney function is restored.
The Impact of Deep Y Descent on Hemodynamics in Patients With Heart Failure and Preserved Left Ventricular Systolic Function
Authors: Harada Daisuke , Asanoi Hidetsugu , Noto Takahisa , Takagawa Junya
Published: December 2021

Background: Influence of right ventricular diastolic function on the hemodynamics of heart failure (HF). We aimed to clarify the hemodynamic features of deep Y descent in the right atrial pressure waveform in patients with HF and preserved left ventricular systolic function.

Methods: In total, 114 consecutive inpatients with HF who had preserved left ventricular systolic function (left ventricular ejection fraction ≥ 50%) and right heart catheterization were retrospectively enrolled in this study. The patients were divided into two groups according to right atrial pressure waveform, and those with Y descent deeper than X descent in the right atrial pressure waveform were assigned to the deep Y descent group. We enrolled another seven patients (two men, five women; mean age, 87 ± 6) with HF and preserved ejection fraction, and implanted a pacemaker to validate the results of this study.

Results: The patients with deep Y descent had a higher rate of atrial fibrillation, higher right atrial pressure and mean pulmonary arterial pressure, and lower stroke volume and cardiac index than those with normal Y descent (76 vs. 7% p < 0.001, median 8 vs. 5 mmHg p = 0.001, median 24 vs. 21 mmHg p = 0.036, median 33 vs. 43 ml/m2p < 0.001, median 2.2 vs. 2.7 L/m2, p < 0.001). Multiple linear regression revealed a negative correlation between stroke volume index and pulmonary vascular resistance index (wood unit*m2) only in the patients with deep Y descent (estimated regression coefficient: −1.281, p = 0.022). A positive correlation was also observed between cardiac index and heart rate in this group (r = 0.321, p = 0.038). In the other seven patients, increasing the heart rate (from median 60 to 80/min, p = 0.001) significantly reduced the level of BNP (from median 419 to 335 pg/ml, p = 0.005).

Conclusions: The hemodynamics of patients with HF with deep Y descent and preserved left ventricular systolic function resembled right ventricular restrictive physiology. Optimizing the heart rate may improve hemodynamics in these patients.
Medicine-Based Evidence in Congenital Heart Disease: How Artificial Intelligence Can Guide Treatment Decisions for Individual Patients
Authors: Van den Eynde Jef , Manlhiot Cedric , Van De Bruaene Alexander , Diller Gerhard-Paul , Frangi Alejandro F. , Budts Werner , Kutty Shelby
Published: December 2021

Built on the foundation of the randomized controlled trial (RCT), Evidence Based Medicine (EBM) is at its best when optimizing outcomes for homogeneous cohorts of patients like those participating in an RCT. Its weakness is a failure to resolve a clinical quandary: patients appear for care individually, each may differ in important ways from an RCT cohort, and the physician will wonder each time if following EBM will provide best guidance for this unique patient. In an effort to overcome this weakness, and promote higher quality care through a more personalized approach, a new framework has been proposed: Medicine-Based Evidence (MBE). In this approach, big data and deep learning techniques are embraced to interrogate treatment responses among patients in real-world clinical practice. Such statistical models are then integrated with mechanistic disease models to construct a “digital twin,” which serves as the real-time digital counterpart of a patient. MBE is thereby capable of dynamically modeling the effects of various treatment decisions in the context of an individual's specific characteristics. In this article, we discuss how MBE could benefit patients with congenital heart disease, a field where RCTs are difficult to conduct and often fail to provide definitive solutions because of a small number of subjects, their clinical complexity, and heterogeneity. We will also highlight the challenges that must be addressed before MBE can be embraced in clinical practice and its full potential can be realized.
Deglacial Land-Ocean Linkages at the Alaskan Continental Margin in the Bering Sea
Authors: Wang Rong , Kuhn Gerhard , Gong Xun , Biskaborn Boris K. , Gersonde Rainer , Lembke-Jene Lester , Lohmann Gerrit , Tiedemann Ralf , Diekmann Bernhard
Published: December 2021

A marine sediment record from the central Bering Sea, spanning the last 20 thousand years (ka), was studied to unravel the depositional history with regard to terrigenous sediment supply and biogenic sedimentation. Methodic approaches comprised the inference of accumulation rates of siliciclastic and biogenic components, grain-size analysis, and (clay) mineralogy, as well as paleoclimatic modelling. Changes in the depositional history provides insight into land-ocean linkages of paleoenvironmental changes. During the finale of the Last Glacial Maximum, the depositional environment was characterized by hemipelagic background sedimentation. A marked change in the terrigenous sediment provenance during the late Heinrich 1 Stadial (15.7–14.5 ka), indicated by increases in kaolinite and a high glaciofluvial influx of clay, gives evidence of the deglaciation of the Brooks Range in the hinterland of Alaska. This meltwater pulse also stimulated the postglacial onset of biological productivity. Glacial melt implies regional climate warming during a time of widespread cooling on the northern hemisphere. Our simulation experiment with a coupled climate model suggests atmospheric teleconnections to the North Atlantic, with impacts on the dynamics of the Aleutian Low system that gave rise to warmer winters and an early onset of spring during that time. The late deglacial period between 14.5 and 11.0 ka was characterized by enhanced fluvial runoff and biological productivity in the course of climate amelioration, sea-level rise, seasonal sea-ice retreat, and permafrost thaw in the hinterland. The latter processes temporarily stalled during the Younger Dryas stadial (12.9-11.7 ka) and commenced again during the Preboreal (earliest Holocene), after 11.7 ka. High river runoff might have fertilized the Bering Sea and contributed to enhanced upper ocean stratification. Since 11.0 ka, advanced transgression has shifted the coast line and fluvial influence of the Yukon River away from the study site. The opening of the Bering Strait strengthened contour currents along the continental slope, leaving behind winnowed sand-rich sediments through the early to mid-Holocene, with non-deposition occurring since about 6.0 ka.
The Role of Time-Series L-Band SAR and GEDI in Mapping Sub-Tropical Above-Ground Biomass
Authors: Khati Unmesh , Lavalle Marco , Singh Gulab
Published: December 2021

Physics-based algorithms estimating large-scale forest above-ground biomass (AGB) from synthetic aperture radar (SAR) data generally use airborne laser scanning (ALS) or grid of national forest inventory (NFI) to reduce uncertainties in the model calibration. This study assesses the potential of multitemporal L-band ALOS-2/PALSAR-2 data to improve forest AGB estimation using the three-parameter water cloud model (WCM) trained with field data from relatively small (0.1 ha) plots. The major objective is to assess the impact of the high uncertainties in field inventory data due to relatively smaller plot size and temporal gap between acquisitions and ground truth on the AGB estimation. This study analyzes a time series of twenty-three ALOS-2 dual-polarized images spanning 5 years acquired under different weather and soil moisture conditions over a subtropical forest test site in India. The WCM model is trained and validated on individual acquisitions to retrieve forest AGB. The accuracy of the generated AGB products is quantified using the root mean square error (RMSE). Further, we use a multitemporal AGB retrieval approach to improve the accuracy of the estimated AGB. Changes in precipitation and soil moisture affect the AGB retrieval accuracy from individual acquisitions; however, using multitemporal data, these effects are mitigated. Using a multitemporal AGB retrieval strategy, the accuracy improves by 15% (55 Mg/ha RMSE) for all field plots and by 21% (39 Mg/ha RMSE) for forests with AGB less than 100 Mg/ha. The analysis shows that any ten multitemporal acquisitions spanning 5 years are sufficient for improving AGB retrieval accuracy over the considered test site. Furthermore, we use allometry from colocated field plots and Global Ecosystem Dynamics Investigation (GEDI) L2A height metrics to produce GEDI-derived AGB estimates. Despite the limited co-location of GEDI and field data over our study area, within the period of interest, the preliminary analysis shows the potential of jointly using the GEDI-derived AGB and multi-temporal ALOS-2 data for large-scale AGB retrieval.