bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk assessment in precapillary pulmonary hypertension: a comparative analysis
Authors: Sonnweber Thomas , Schneider Eva-Maria , Nairz Manfred , Theurl Igor , Weiss Günter , Tymoszuk Piotr , Löffler-Ragg Judith
Published: January 2021

Background

Risk stratification is essential to assess mortality risk and guide treatment in patients with precapillary pulmonary hypertension (PH). We herein compared the accuracy of different currently used PH risk stratification tools and evaluated the significance of particular risk parameters.

Methods

We conducted a retrospective longitudinal observational cohort study evaluating seven different risk assessment approaches according to the current PH guidelines. A comprehensive assessment including multi-parametric risk stratification was performed at baseline and 4 yearly follow-up time-points. Multi-step Cox hazard analysis was used to analyse and refine risk prediction.

Results

Various available risk models effectively predicted mortality in patients with precapillary pulmonary hypertension. Right-heart catheter parameters were not essential for risk prediction. Contrary, non-invasive follow-up re-evaluations significantly improved the accuracy of risk estimations. A lack of accuracy of various risk models was found in the intermediate- and high-risk classes. For these patients, an additional evaluation step including assessment of age and right atrium area improved risk prediction significantly.

Discussion

Currently used abbreviated versions of the ESC/ERS risk assessment tool, as well as the REVEAL 2.0 and REVEAL Lite 2 based risk stratification, lack accuracy to predict mortality in intermediate- and high-risk precapillary pulmonary hypertension patients. An expanded non-invasive evaluation improves mortality risk prediction in these individuals.
Impact of insulin resistance on subclinical left ventricular dysfunction in normal weight and overweight/obese japanese subjects in a general community
Authors: Hirose Kazutoshi , Nakanishi Koki , Daimon Masao , Sawada Naoko , Yoshida Yuriko , Iwama Kentaro , Yamamoto Yuko , Ishiwata Jumpei , Hirokawa Megumi , Koyama Katsuhiro , Nakao Tomoko , Morita Hiroyuki , Di Tullio Marco R. , Homma Shunichi , Komuro Issei
Published: January 2021

Background

Insulin resistance carries increased risk of heart failure, although the pathophysiological mechanisms remain unclear. LV global longitudinal strain (LVGLS) assessed by speckle-tracking echocardiography has emerged as an important tool to detect early LV systolic abnormalities. This study aimed to investigate the association between insulin resistance and subclinical left ventricular (LV) dysfunction in a sample of the general population without overt cardiac disease.

Methods

We investigated 539 participants who voluntarily underwent extensive cardiovascular health check including laboratory test and speckle-tracking echocardiography. Glycemic profiles were categorized into 3 groups according to homeostatic model assessment of insulin resistance (HOMA-IR): absence of insulin resistance (HOMA-IR < 1.5), presence of insulin resistance (HOMA-IR ≥ 1.5) and diabetes mellitus (DM). Multivariable logistic regression models were conducted to evaluate the association between abnormal glucose metabolism and impaired LVGLS (> − 16.65%).

Results

Forty-five (8.3%) participants had DM and 66 (12.2%) had abnormal HOMA-IR. LV mass index and E/e′ ratio did not differ between participants with and without abnormal HOMA-IR, whereas abnormal HOMA-IR group had significantly decreased LVGLS (− 17.6 ± 2.6% vs. − 19.7 ± 3.1%, p < 0.05). The prevalence of impaired LVGLS was higher in abnormal HOMA-IR group compared with normal HOMA-IR group (42.4% vs. 14.0%) and similar to that of DM (48.9%). In multivariable analyses, glycemic abnormalities were significantly associated with impaired LVGLS, independent of traditional cardiovascular risk factors and pertinent laboratory and echocardiographic parameters [adjusted odds ratio (OR) 2.38, p = 0.007 for abnormal HOMA-IR; adjusted OR 3.02, p = 0.003 for DM]. The independent association persisted even after adjustment for waist circumference as a marker of abdominal adiposity. Sub-group analyses stratified by body mass index showed significant association between abnormal HOMA-IR and impaired LVGLS in normal weight individuals (adjusted OR 4.59, p = 0.001), but not in overweight/obese individuals (adjusted OR 1.62, p = 0.300).

Conclusions

In the general population without overt cardiac disease, insulin resistance carries independent risk for subclinical LV dysfunction, especially in normal weight individuals.
Factors associated with access and adherence to artemisinin‐based combination therapy (ACT) for children under five: a secondary analysis of a national survey in Sierra Leone
Authors: Banek Kristin , Webb Emily L. , Doogue Emily Bostick , Smith Samuel Juana , Chandramohan Daniel , Staedke Sarah G.
Published: January 2021

Background

Access and adherence to artemisinin-based combination therapy (ACT) are key challenges to effective malaria treatment. A secondary analysis of the Sierra Leone malaria Knowledge, Attitudes, and Practices (mKAP) survey was conducted to investigate access and adherence to ACT for the treatment of fever in children under-five.

Methods

The mKAP was a nationally representative, two-stage cluster-sample survey, conducted in 2012. Thirty primary sampling units per district were randomly selected using probability proportionate to size, based on national census estimates; 14 households were subsequently randomly selected and enrolled per sampling unit. The analysis was restricted to children under-five with fever in the past two weeks. Factors associated with access and adherence were assessed using multivariate logistic regression.

Results

Of 5169 enrolled households, 1456 reported at least one child under-five with fever in the past two weeks. Of the 1641 children from these households, 982 (59.8%) received any treatment for fever and were analysed for access to ACT; 469 (47.6%) received ACT and 466 were analysed for treatment adherence. Only 222 (47.4%) febrile children received ACT and completed 3-day treatment. In an adjusted analysis, factors associated with ACT access included knowledge of ACT (odds ratio [OR] 2.78, 95% CI 2.02–3.80; p < 0.001), knowledge of insecticide-treated nets (ITNs) (OR 1.84, 95% CI 1.29–2.63; p = 0.001), source of care (public health facility vs. other; OR 1.86, 95% CI 1.27–2.72, p = 0.001), geographic region (East vs. West; OR 2.30, 95% CI 1.20–4.44; p = 0.025), and age (24–59 vs. 0–23 months; OR 1.45, 95% CI 1.07–1.96; p = 0.016). The only factor associated with ACT adherence was time to treatment; children treated within 24 h were less likely to adhere (OR 0.55, 95% CI 0.34–0.89; p = 0.015).

Conclusions

In 2012, access and adherence to ACT remained low in Sierra Leone. Knowledge of ACT and ITNs, and seeking care in the public sector, were most strongly associated with ACT access. National surveys provide important information on anti-malarial access and could be expanded to measure treatment adherence.
Laparoscopic-assisted disinvagination and polypectomy for multiple intussusceptions induced by small intestinal polyps in patients with Peutz-Jeghers syndrome: a case report
Authors: Yamamoto Masaaki , Iwamoto Kazuya , Suzuki Rei , Mukai Yosuke , Takeoka Tomohira , Asukai Kei , Shinno Naoki , Hara Hisashi , Kanemura Takashi , Nakai Nozomu , Hasegawa Shinichiro , Sugimura Keijiro , Haraguchi Naotsugu , Nishimura Junichi , Wada Hiroshi , Takahashi Hidenori , Matsuda Chu , Yasui Masayoshi , Omori Takeshi , Miyata Hiroshi , Ohue Masayuki , Murata Masaru
Published: January 2021

Background

Peutz–Jeghers syndrome (PJS) is a very rare autosomal dominant genetic disorder characterized by hamartomatous polyps in the gastrointestinal tract and hyperpigmentation of the lips, hands, and feet. The hamartomatous polyps in the small intestine often cause intussusception and bleeding.

Case presentation

A 62-year-old male was hospitalized for treatment of deep vein thrombosis and pulmonary embolism. In the small intestine, computed tomography showed three small polyps with intussusceptions. Since the patient had gastrointestinal polyposis and pigmentation of his lips, fingers, and toes, he was diagnosed with PJS. After an inferior vena cava filter was placed, he underwent laparoscopic-assisted surgery. The polyps causing intussusception were resected as far as possible without intestinal resection, since they had caused progressive anemia and might cause intestinal obstruction in the future. The patient was discharged from the hospital on postoperative day 9 without complications.

Conclusions

Laparoscopic-assisted disinvagination and polypectomy is a useful, minimally invasive treatment for multiple intussusceptions caused by small intestinal polyps in patients with PJS.
Patient-derived organoid (PDO) platforms to facilitate clinical decision making
Authors: Liu Lisa , Yu Lei , Li Zhichao , Li Wujiao , Huang WeiRen
Published: January 2021

Based on recent advances in organoid research as well as the need to find more accurate models for drug screening in cancer research, patient-derived organoids have emerged as an effective in vitro model system to study cancer. Showing numerous advantages over 2D cell lines, 3D cell lines, and primary cell culture, organoids have been applied in drug screening to demonstrate the correlation between genetic mutations and sensitivity to targeted therapy. Organoids have also been used in co-clinical trials to compare drug responses in organoids to clinical responses in the corresponding patients. Numerous studies have reported the successful use of organoids to predict therapy response in cancer patients. Recently, organoids have been adopted to predict treatment response to radiotherapy and immunotherapy. The development of high throughput drug screening and organoids-on-a-chip technology can advance the use of patient-derived organoids in clinical practice and facilitate therapeutic decision-making.
Predicting the number of article citations in the field of attention-deficit/hyperactivity disorder (ADHD) with the 100 top-cited articles since 2014: a bibliometric analysis
Authors: Lin Chien-Ho , Chien Tsair-Wei , Yan Yu-Hua
Published: January 2021

Background

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in children or early adolescents with an estimated worldwide prevalence of 7.2%. Numerous articles related to ADHD have been published in the literature. However, which articles had ultimate influence is still unknown, and what factors affect the number of article citations remains unclear as well. This bibliometric analysis (1) visualizes the prominent entities with 1 picture using the top 100 most-cited articles, and (2) investigates whether medical subject headings (i.e., MeSH terms) can be used in predicting article citations.

Methods

By searching the PubMed Central® (PMC) database, the top 100 most-cited abstracts relevant to ADHD since 2014 were downloaded. Citation rank analysis was performed to compare the dominant roles of article types and topic categories using the pyramid plot. Social network analysis (SNA) was performed to highlight prominent entities for providing a quick look at the study result. The authors examined the MeSH prediction effect on article citations using its correlation coefficients (CC).

Results

The most frequent article types and topic categories were research support by institutes (56%) and epidemiology (28%). The most productive countries were the United States (42%), followed by the United Kingdom (13%), Germany (9%), and the Netherlands (9%). Most articles were published in the Journal of the American Academy of Child and Adolescent Psychiatry (15%) and JAMA Psychiatry (9%). MeSH terms were evident in prediction power on the number of article citations (correlation coefficient = 0.39; t = 4.1; n = 94; 6 articles were excluded because they do not have MeSH terms).

Conclusions

The breakthrough was made by developing 1 dashboard to display 100 top-cited articles on ADHD. MeSH terms can be used in predicting article citations on ADHD. These visualizations of the top 100 most-cited articles could be applied to future academic pursuits and other academic disciplines.
HSP22 (HSPB8) positively regulates PGF2α-induced synthesis of interleukin-6 and vascular endothelial growth factor in osteoblasts
Authors: Kuroyanagi Gen , Sakai Go , Otsuka Takanobu , Yamamoto Naohiro , Fujita Kazuhiko , Kawabata Tetsu , Matsushima-Nishiwaki Rie , Kozawa Osamu , Tokuda Haruhiko
Published: January 2021

Background

Heat shock protein 22 (HSP22) belongs to class I of the small HSP family that displays ubiquitous expression in osteoblasts. We previously demonstrated that prostaglandin F2α (PGF2α), a potent bone remodeling factor, induces the synthesis of interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) via p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether HSP22 is implicated in the PGF2α-induced synthesis of IL-6 and VEGF and the mechanism of MC3T3-E1 cells.

Methods

MC3T3-E1 cells were transfected with HSP22-siRNA. IL-6 and VEGF release was assessed by ELISA. Phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was detected by Western blotting.

Results

The PGF2α-induced release of IL-6 in HSP22 knockdown cells was significantly suppressed compared with that in the control cells. HSP22 knockdown also reduced the VEGF release by PGF2α. Phosphorylation of p44/p42 MAP kinase and p38 MAP kinase was attenuated by HSP22 downregulation.

Conclusions

Our results strongly suggest that HSP22 acts as a positive regulator in the PGF2α-induced synthesis of IL-6 and VEGF in osteoblasts.
Unilateral percutaneous vertebroplasty for osteoporotic lumbar compression fractures: a comparative study between transverse process root-pedicle approach and conventional transpedicular approach
Authors: Zhang Wenwu , Liu Shenpeng , Liu Xianhua , Li Xiang , Wang Le , Wan Yong
Published: January 2021

Purpose

Percutaneous vertebroplasty (PVP) is a routine operation for the treatment of osteoporotic lumbar compression fractures (OLCFs). As is well known, unilateral puncture is a common method. However, with the conventional transpedicular approach (CTPA), the cement may be asymmetrically dispersed, so some surgeons use the transverse process root-pedicle approach (TPRPA). The objective of this study was to compare the clinical results and bone cement distribution of PVP for OLCF with unilateral TPRPA and CTPA to identify the advantages and disadvantages of the two surgical options.

Patients and methods

From January 2016 to June 2019, seventy-two elderly patients who underwent unilateral PVP for single-level OLCF were retrospectively reviewed. Operation time, injection amount and type of bone cement distribution, and bone cement leakage and surgical complications were recorded. The visual analog scale (VAS) scores and Oswestry disability index (ODI) scores were used to evaluate the clinical results. All patients were followed up for more than 12 months, and the assessment was based primarily on clinical and radiological outcomes.

Results

There were significant differences in the surgical time and the volume and the type of bone cement distribution and the lost of operative vertebra height between the two groups. However, there was no significant difference in bone cement leakage. Moreover, there were no significant differences in VAS and ODI between the two groups at 2 days and 12 months after the operation.

Conclusions

Unilateral TPRPA and CTPA are practical and feasible methods in PVP for the treatment of OLCF, and they have similar clinical effects. However, TPRPA has the advantages of a better distribution of bone cement and a shorter operation time and a better maintenance effect of injured vertebra height, without increasing the rate of bone cement leakage.
Impact of long-term elosulfase alfa treatment on clinical and patient-reported outcomes in patients with mucopolysaccharidosis type IVA: results from a Managed Access Agreement in England
Authors: Cleary Maureen , Davison James , Gould Rachel , Geberhiwot Tarekegn , Hughes Derralynn , Mercer Jean , Morrison Alexandra , Murphy Elaine , Santra Saikat , Jarrett James , Mukherjee Swati , Stepien Karolina M.
Published: January 2021

Background

We present baseline characteristics and follow-up data of a Managed Access Agreement (MAA), including patients with mucopolysaccharidosis IVA (MPS IVA) receiving elosulfase alfa enzyme replacement therapy (ERT) in England on a conditional basis. Patients enrolled in the MAA programme are reviewed on an annual basis. Therapy can be continued if patients are compliant, able to tolerate infusions, and meet four out of five pre-defined clinical and patient-reported outcomes (PRO) criteria. Baseline and follow-up clinical and PRO data are presented for all participants who completed ≥ 1 year of assessments in the MAA.

Results

The analysis included data from 55 patients, including 26 patients previously enrolled in clinical trials and 29 who started ERT after enrolling in the MAA. In patients with both baseline and follow-up data, mean 6-min walk test distance increased from 217 m at baseline to 244 m after a mean follow-up of 4.9 years. Improvement or stabilisation was seen regardless of age at treatment initiation or duration of treatment. Mean forced vital capacity and forced expiratory volume in 1 s were 0.87 L and 0.78 L, respectively at baseline and 1.05 L and 0.88 L after a mean follow-up of 5.5 years. PRO data showed overall improvements over time in Mobility, Self-care, and Caregiver assistance scores of the MPS-Health Assessment Questionnaire, relatively stable quality of life, and some improvements in pain scores.

Conclusions

The MAA data confirm the effects of elosulfase alfa on clinical and PRO results observed in the clinical trials and provide real-world evidence for long-term stabilisation in these measures, suggesting a positive impact on the natural history of MPS IVA.
PDGFRβ is an essential therapeutic target for BRCA1-deficient mammary tumors
Authors: Bai Feng , Liu Shiqin , Liu Xiong , Hollern Daniel P. , Scott Alexandria , Wang Chuying , Zhang Lihan , Fan Cheng , Fu Li , Perou Charles M. , Zhu Wei-Guo , Pei Xin-Hai
Published: January 2021

Background

Basal-like breast cancers (BLBCs) are a leading cause of cancer death due to their capacity to metastasize and lack of effective therapies. More than half of BLBCs have a dysfunctional BRCA1. Although most BRCA1-deficient cancers respond to DNA-damaging agents, resistance and tumor recurrence remain a challenge to survival outcomes for BLBC patients. Additional therapies targeting the pathways aberrantly activated by BRCA1 deficiency are urgently needed.

Methods

Most BRCA1-deficient BLBCs carry a dysfunctional INK4-RB pathway. Thus, we created genetically engineered mice with Brca1 loss and deletion of p16INK4A, or separately p18INK4C, to model the deficient INK4-RB signaling in human BLBC. By using these mutant mice and human BRCA1-deficient and proficient breast cancer tissues and cells, we tested if there exists a druggable target in BRCA1-deficient breast cancers.

Results

Heterozygous germline or epithelium-specific deletion of Brca1 in p18INK4C- or p16INK4A-deficient mice activated Pdgfrβ signaling, induced epithelial-to-mesenchymal transition, and led to BLBCs. Confirming this role, targeted deletion of Pdgfrβ in Brca1-deficient tumor cells promoted cell death, induced mesenchymal-to-epithelial transition, and suppressed tumorigenesis. Importantly, we also found that pharmaceutical inhibition of Pdgfrβ and its downstream target Pkcα suppressed Brca1-deficient tumor initiation and progression and effectively killed BRCA1-deficient cancer cells.

Conclusions

Our work offers the first genetic and biochemical evidence that PDGFRβ-PKCα signaling is repressed by BRCA1, which establishes PDGFRβ-PKCα signaling as a therapeutic target for BRCA1-deficient breast cancers.
Optimized RNA-targeting CRISPR/Cas13d technology outperforms shRNA in identifying functional circRNAs
Authors: Zhang Yang , Nguyen Tuan M. , Zhang Xiao-Ou , Wang Limei , Phan Tin , Clohessy John G. , Pandolfi Pier Paolo
Published: January 2021

Short hairpin RNAs (shRNAs) are used to deplete circRNAs by targeting back-splicing junction (BSJ) sites. However, frequent discrepancies exist between shRNA-mediated circRNA knockdown and the corresponding biological effect, querying their robustness. By leveraging CRISPR/Cas13d tool and optimizing the strategy for designing single-guide RNAs against circRNA BSJ sites, we markedly enhance specificity of circRNA silencing. This specificity is validated in parallel screenings by shRNA and CRISPR/Cas13d libraries. Using a CRISPR/Cas13d screening library targeting > 2500 human hepatocellular carcinoma-related circRNAs, we subsequently identify a subset of sorafenib-resistant circRNAs. Thus, CRISPR/Cas13d represents an effective approach for high-throughput study of functional circRNAs.
Synthesis and biological evaluation of heterocyclic 1,2,4-triazole scaffolds as promising pharmacological agents
Authors: Kumari Mukesh , Tahlan Sumit , Narasimhan Balasubramanian , Ramasamy Kalavathy , Lim Siong Meng , Shah Syed Adnan Ali , Mani Vasudevan , Kakkar Saloni
Published: January 2021

Background

Triazole is an important heterocyclic moiety that occupies a unique position in heterocyclic chemistry, due to its large number of biological activities. It exists in two isomeric forms i.e. 1,2,4-triazole and 1,2,3-triazole and is used as core molecule for the design and synthesis of many medicinal compounds. 1,2,4-Triazole possess broad spectrum of therapeutically interesting drug candidates such as analgesic, antiseptic, antimicrobial, antioxidant, anti-urease, anti-inflammatory, diuretics, anticancer, anticonvulsant, antidiabetic and antimigraine agents.

Methods

The structures of all synthesized compounds were characterized by physicochemical properties and spectral means (IR and NMR). The synthesized compounds were evaluated for their in vitro antimicrobial activity against Gram-positive (B. subtilis), Gram-negative (P. aeruginosa and E. coli) bacterial and fungal (C. albicans and A. niger) strains by tube dilution method using ciprofloxacin, amoxicillin and fluconazole as standards. In-vitro antioxidant and anti-urease screening was done by DPPH assay and indophenol method, respectively. The in-vitro anticancer evaluation was carried out against MCF-7 and HCT116 cancer cell lines using 5-FU as standards.

Results, discussion and conclusion

The biological screening results reveal that the compounds T5 (MICBS, EC = 24.7 µM, MICPA, CA = 12.3 µM) and T17 (MICAN = 27.1 µM) exhibited potent antimicrobial activity as comparable to standards ciprofloxacin, amoxicillin (MICCipro = 18.1 µM, MICAmo = 17.1 µM) and fluconazole (MICFlu = 20.4 µM), respectively. The antioxidant evaluation showed that compounds T2 (IC50 = 34.83 µg/ml) and T3 (IC50 = 34.38 µg/ml) showed significant antioxidant activity and comparable to ascorbic acid (IC50 = 35.44 µg/ml). Compounds T3 (IC50 = 54.01 µg/ml) was the most potent urease inhibitor amongst the synthesized compounds and compared to standard thiourea (IC50 = 54.25 µg/ml). The most potent anticancer activity was shown by compounds T2 (IC50 = 3.84 μM) and T7 (IC50 = 3.25 μM) against HCT116 cell lines as compared to standard 5-FU (IC50 = 25.36 μM).
Unraveling the roles of the reductant and free copper ions in LPMO kinetics
Authors: Stepnov Anton A. , Forsberg Zarah , Sørlie Morten , Nguyen Giang-Son , Wentzel Alexander , Røhr Åsmund K. , Eijsink Vincent G. H.
Published: January 2021

Background

Lytic polysaccharide monooxygenases (LPMOs) are monocopper enzymes that catalyze oxidative depolymerization of industrially relevant crystalline polysaccharides, such as cellulose, in a reaction that depends on an electron donor and O2or H2O2. While it is well known that LPMOs can utilize a wide variety of electron donors, the variation in reported efficiencies of various LPMO-reductant combinations remains largely unexplained.

Results

In this study, we describe a novel two-domain cellulose-active family AA10 LPMO from a marine actinomycete, which we have used to look more closely at the effects of the reductant and copper ions on the LPMO reaction. Our results show that ascorbate-driven LPMO reactions are extremely sensitive to very low amounts (micromolar concentrations) of free copper because reduction of free Cu(II) ions by ascorbic acid leads to formation of H2O2, which speeds up the LPMO reaction. In contrast, the use of gallic acid yields steady reactions that are almost insensitive to the presence of free copper ions. Various experiments, including dose–response studies with the enzyme, showed that under typically used reaction conditions, the rate of the reaction is limited by LPMO-independent formation of H2O2resulting from oxidation of the reductant.

Conclusion

The strong impact of low amounts of free copper on LPMO reactions with ascorbic acid and O2, i.e. the most commonly used conditions when assessing LPMO activity, likely explains reported variations in LPMO rates. The observed differences between ascorbic acid and gallic acid show a way of making LPMO reactions less copper-dependent and illustrate that reductant effects on LPMO action need to be interpreted with great caution. In clean reactions, with minimized generation of H2O2, the (O2-driven) LPMO reaction is exceedingly slow, compared to the much faster peroxygenase reaction that occurs when adding H2O2.
The usefulness of measuring the anion gap in diagnosing metformin-associated lactic acidosis: a case series
Authors: Ruiz-Ramos Jesus , Lozano-Polo Laura , Juanes-Borrego Ana , Agra-Montava Iván , Puig-Campmany Mireia , Mangues-Bafalluy María Antonia
Published: January 2021

Background

Metformin-associated lactic acidosis (MALA) is a widely documented adverse event of metformin. Despite being considered one of the main causes of metabolic acidosis, the association between an anion gap and MALA diagnosis is still uncertain.

Case presentation

Cases involving six Caucasian patients with suspected MALA who were admitted to the emergency department were analysed. All these patients presented with pH values < 7.35, lactate levels > 2 mmol/L, and estimated glomerular filtration < 30 mL/min. Metformin plasma concentrations were > 2.5 mg/L in all the patients. The highest metformin concentrations were not found in the patients with the highest lactate levels. The anion gap values ranged from 12.3 to 39.3, with only two patients exhibiting values > 14.

Conclusions

In patients with MALA, there is a significant variability in the anion gap values, which is not related to the level of metformin accumulation, and therefore, it is doubtful whether measuring anion gaps is useful as an approach for MALA diagnosis.
Intrusion detection in internet of things using supervised machine learning based on application and transport layer features using UNSW-NB15 data-set
Authors: Ahmad Muhammad , Riaz Qaiser , Zeeshan Muhammad , Tahir Hasan , Haider Syed Ali , Khan Muhammad Safeer
Published: January 2021

Internet of Things (IoT) devices are well-connected; they generate and consume data which involves transmission of data back and forth among various devices. Ensuring security of the data is a critical challenge as far as IoT is concerned. Since IoT devices are inherently low-power and do not require a lot of compute power, a Network Intrusion Detection System is typically employed to detect and remove malicious packets from entering the network. In the same context, we propose feature clusters in terms of Flow, Message Queuing Telemetry Transport (MQTT) and Transmission Control Protocol (TCP) by using features in UNSW-NB15 data-set. We eliminate problems like over-fitting, curse of dimensionality and imbalance in the data-set. We apply supervised Machine Learning (ML) algorithms, i.e., Random Forest (RF), Support Vector Machine and Artificial Neural Networks on the clusters. Using RF, we, respectively, achieve 98.67% and 97.37% of accuracy in binary and multi-class classification. In clusters based techniques, we achieved 96.96%, 91.4% and 97.54% of classification accuracy by using RF on Flow & MQTT features, TCP features and top features from both clusters. Moreover, we show that the proposed feature clusters provide higher accuracy and requires lesser training time as compared to other state-of-the-art supervised ML-based approaches.
Design of intelligent diagnosis system for teaching quality based on wireless sensor network and data mining
Authors: Zhang Yanping , Huang Wanwei
Published: January 2021

With the popularization of computers and various mobile intelligent terminals, intelligent teaching systems based on learners are becoming more and more popular among learners. The above phenomenon has greatly affected and changed the current teaching quality diagnosis methods and models. However, the author found through investigation that the current intelligent teaching quality diagnosis still has different degrees of deficiencies in the design and implementation. In response to the above problems, this paper proposes a teaching quality intelligent diagnosis model based on the combination of wireless sensor networks and fuzzy comprehensive evaluation algorithms. First of all, this article is based on the wireless sensor network to link various levels of intelligent teaching systems, and constructs the information transmission structure of the teaching intelligent diagnosis system. Secondly, this article uses fuzzy comprehensive evaluation and convolutional neural network algorithms to evaluate and excavate intelligent teaching information. Finally, the model successfully passed the simulation test and simulation application, which can provide intelligent diagnosis of teaching quality for modern intelligent teaching system.
A new approach on the modelling, chaos control and synchronization of a fractional biological oscillator
Authors: Alshomrani Ali Saleh , Ullah Malik Zaka , Baleanu Dumitru
Published: January 2021

This research aims to discuss and control the chaotic behaviour of an autonomous fractional biological oscillator. Indeed, the concept of fractional calculus is used to include memory in the modelling formulation. In addition, we take into account a new auxiliary parameter in order to keep away from dimensional mismatching. Further, we explore the chaotic attractors of the considered model through its corresponding phase-portraits. Additionally, the stability and equilibrium point of the system are studied and investigated. Next, we design a feedback control scheme for the purpose of chaos control and stabilization. Afterwards, we introduce an efficient active control method to achieve synchronization between two chaotic fractional biological oscillators. The efficiency of the proposed stabilizing and synchronizing controllers is verified via theoretical analysis as well as simulations and numerical experiments.
Diffusion-weighted MRI improves response assessment after definitive radiotherapy in patients with NSCLC
Authors: Jagoda Philippe , Fleckenstein Jochen , Sonnhoff Mathias , Schneider Günther , Ruebe Christian , Buecker Arno , Stroeder Jonas
Published: January 2021

Background

Computed tomography (CT) is the standard procedure for follow-up of non-small-cell lung cancer (NSCLC) after radiochemotherapy. CT has difficulties differentiating between tumor, atelectasis and radiation induced lung toxicity (RILT). Diffusion-weighted imaging (DWI) may enable a more accurate detection of vital tumor tissue. The aim of this study was to determine the diagnostic value of MRI versus CT in the follow-up of NSCLC.

Methods

Twelve patients with NSCLC stages I-III scheduled for radiochemotherapy were enrolled in this prospective study. CT with i.v. contrast agent and non enhanced MRI were performed before and 3, 6 and 12 months after treatment. Standardized ROIs were used to determine the apparent diffusion weighted coefficient (ADC) within the tumor. Tumor size was assessed by the longest longitudinal diameter (LD) and tumor volume on DWI and CT. RILT was assessed on a 4-point-score in breath-triggered T2-TSE and CT.

Results

There was no significant difference regarding LD and tumor volume between MRI and CT (p ≥ 0.6221, respectively p ≥ 0.25). Evaluation of RILT showed a very high correlation between MRI and CT at 3 (r = 0.8750) and 12 months (r = 0.903). Assessment of the ADC values suggested that patients with a good tumor response have higher ADC values than non-responders.

Conclusions

DWI is equivalent to CT for tumor volume determination in patients with NSCLC during follow up. The extent of RILT can be reliably determined by MRI. DWI could become a beneficial method to assess tumor response more accurately. ADC values may be useful as a prognostic marker.
On the usage of average Hausdorff distance for segmentation performance assessment: hidden error when used for ranking
Authors: Aydin Orhun Utku , Taha Abdel Aziz , Hilbert Adam , Khalil Ahmed A. , Galinovic Ivana , Fiebach Jochen B. , Frey Dietmar , Madai Vince Istvan
Published: January 2021

Average Hausdorff distance is a widely used performance measure to calculate the distance between two point sets. In medical image segmentation, it is used to compare ground truth images with segmentations allowing their ranking. We identified, however, ranking errors of average Hausdorff distance making it less suitable for applications in segmentation performance assessment. To mitigate this error, we present a modified calculation of this performance measure that we have coined “balanced average Hausdorff distance”. To simulate segmentations for ranking, we manually created non-overlapping segmentation errors common in magnetic resonance angiography cerebral vessel segmentation as our use-case. Adding the created errors consecutively and randomly to the ground truth, we created sets of simulated segmentations with increasing number of errors. Each set of simulated segmentations was ranked using both performance measures. We calculated the Kendall rank correlation coefficient between the segmentation ranking and the number of errors in each simulated segmentation. The rankings produced by balanced average Hausdorff distance had a significantly higher median correlation (1.00) than those by average Hausdorff distance (0.89). In 200 total rankings, the former misranked 52 whilst the latter misranked 179 segmentations. Balanced average Hausdorff distance is more suitable for rankings and quality assessment of segmentations than average Hausdorff distance.
Can Community Health Workers Increase Palliative Care Use for African American Patients? A Pilot Study
Authors: Sedhom Ramy , Nudotor Richard , Freund Karen M. , Smith Thomas J. , Cooper Lisa A. , Owczarzak Jill T. , Johnston Fabian M.
Published: January 2021

PURPOSE:

African American patients with cancer underutilize advance care planning (ACP) and palliative care (PC). This feasibility study investigated whether community health workers (CHWs) could improve ACP and PC utilization for African American patients with advanced cancer.

METHODS:

African American patients diagnosed with an advanced solid organ cancer (stage IV or stage III disease with a palliative performance score < 60%) were enrolled. Patients completed baseline surveys that assessed symptom burden and distress at baseline and 3 months post-CHW intervention. The CHW intervention consisted of a comprehensive assessment of multiple PC domains and social determinants of health. CHWs provided tailored support and education on the basis of iterative assessment of patient needs. Intervention feasibility was determined by patient and caregiver retention rate above 50% at 3 months.

RESULTS:

Over a 12-month period, 24 patients were screened, of which 21 were deemed eligible. Twelve patients participated in the study. Patient retention was high at 3 months (75%) and 6 months (66%). Following the CHW intervention, symptom assessment as measured by Edmonton Symptom Assessment System improved from 33.8 at baseline to 18.8 ( P = .03). Psychological distress improved from 5.5 to 4.7 ( P = .36), and depressive symptoms from 42.2 to 33.6 ( P = .09), although this was not significant. ACP documentation improved from 25% at baseline to 75% at study completion. Sixty-seven percentage of patients were referred to PC, with 100% of three decedents using hospice.

CONCLUSION:

Utilization of CHWs to address PC domains and social determinants of health is feasible. Although study enrollment was identified as a potential barrier, most recruited patients were retained on study.
Plasma Cell-Free DNA to Differentiate Malignant from Benign Thyroid Nodules
Authors: Dutta Susmita , Tarafdar Soham , Mukhopadhyay Pradip , Bhattacharyya Nitai P , Ghosh Sujoy
Published: January 2021

Background

Molecular testing is increasingly used to identify malignancy in thyroid nodules (especially indeterminate category). Measurement of cell-free DNA (cfDNA) levels from plasma has been useful in diagnosis of cancers of other organs/tissues; herein we analyze cfDNA levels in patients with thyroid nodules to explore the possibility of establishing a cutoff for identification of malignancy.

Methods

Patients underwent ultrasonography (USG) and USG-guided fine needle aspiration as well as surgery, where indicated. Cell-free DNA was extracted from plasma and quantified. In initial analysis (determination of cutoff), cfDNA levels were compared between Bethesda 2 and Bethesda 5 &6 to establish a cutoff value that could differentiate malignant from benign nodules. In the subsequent analysis, the aforementioned cutoff was applied (validation of cutoff) to those with indeterminate nodules to check ability to predict malignancy.

Results

Fine needle aspiration (n = 119) yielded patients with Bethesda 2 (n = 69) Bethesda 5 & 6 (n = 13) who underwent histopathological confirmation. Cell-free DNA levels in these 2 groups were 22.85 ± 1.27 and 96.20 ± 8.31 (ng/mL) respectively. A cfDNA cutoff of 67.9 ng/mL, with area under the curve of 0.992 (95% CI, 0.97-1.0) with 100% sensitivity and 93% specificity was established to identify malignant lesions. Indeterminate group (Bethesda 3 & 4) underwent surgery (malignant n = 24), (benign n = 13), and using the previously identified cutoff for cfDNA, we were able to identify malignant lesions with a sensitivity of 100% and specificity of 92.3%. There was a very strong agreement between cfDNA-based classification with histopathology-based classification of benign and malignant nodules (Cohen’s kappa 0.94; P < 0.001)

Conclusion

Plasma cfDNA estimation could help differentiate malignant from benign thyroid nodules.
Construct Validation of the American Board of Anesthesiology’s APPLIED Examination for Initial Certification
Authors: Wang Ting , Sun Huaping , Zhou Yan , Chen Dandan , Harman Ann E. , Isaak Robert S. , Peterson-Layne Cathleen , Macario Alex , Fahy Brenda G. , Warner David O.
Published: January 2021

BACKGROUND:

The American Board of Anesthesiology administers the APPLIED Examination as a part of initial certification, which as of 2018 includes 2 components—the Standardized Oral Examination (SOE) and the Objective Structured Clinical Examination (OSCE). The goal of this study is to investigate the measurement construct(s) of the APPLIED Examination to assess whether the SOE and the OSCE measure distinct constructs (ie, factors).

METHODS:

Exploratory item factor analysis of candidates’ performance ratings was used to determine the number of constructs, and confirmatory item factor analysis to estimate factor loadings within each construct and correlation(s) between the constructs.

RESULTS:

In exploratory item factor analysis, the log-likelihood ratio test and Akaike information criterion index favored the 3-factor model, with factors reflecting the SOE, OSCE Communication and Professionalism, and OSCE Technical Skills. The Bayesian information criterion index favored the 2-factor model, with factors reflecting the SOE and the OSCE. In confirmatory item factor analysis, both models suggest moderate correlation between the SOE factor and the OSCE factor; the correlation was 0.49 (95% confidence interval [CI], 0.42-0.55) for the 3-factor model and 0.61 (95% CI, 0.54-0.64) for the 2-factor model. The factor loadings were lower for Technical Skills stations of the OSCE (ranging from 0.11 to 0.25) compared with those of the SOE and Communication and Professionalism stations of the OSCE (ranging from 0.36 to 0.50).

CONCLUSIONS:

The analyses provide evidence that the SOE and the OSCE measure distinct constructs, supporting the rationale for administering both components of the APPLIED Examination for initial certification in anesthesiology.
Trends in Peripheral Nerve Block Usage in Mastectomy and Lumpectomy: Analysis of a National Database From 2010 to 2018
Authors: Lam Stephanie , Qu Helena , Hannum Margaret , Tan Kay See , Afonso Anoushka , Tokita Hanae K. , McCormick Patrick J.
Published: January 2021

BACKGROUND:

Compared to general anesthesia, regional anesthesia confers several benefits including improved pain control and decreased postoperative opioid consumption. While the benefits of peripheral nerve blocks (PNB) have been well studied, there are little epidemiological data on PNB usage in mastectomy and lumpectomy procedures. The primary objective of our study was to assess national trends of the annual proportion of PNB use in breast surgery from 2010 to 2018. We also identified factors associated with PNB use for breast surgery.

METHODS:

We identified lumpectomy and mastectomy surgical cases with and without PNB between 2010 and 2018 using the Anesthesia Quality Institute National Anesthesia Clinical Outcomes Registry (AQI NACOR). We modeled the nonlinear association between year of procedure and PNB use with segmented mixed-effects logistic regression clustered on facility identifier. The association between PNB use and year of procedure, age, sex, American Society of Anesthesiologists physical status (ASA PS), facility type, facility region, weekday, and tissue expander use was also modeled using mixed-effects logistic regression.

RESULTS:

Of the 189,854 surgical cases from 2010 to 2018 that met criteria, 86.2% were lumpectomy cases and 13.8% were mastectomy cases. The proportion of lumpectomy cases with PNB was <0.1% in 2010 and increased each subsequent year to 1.9% in 2018 (trend P < .0001). The proportion of mastectomy cases with PNB was 0.5% in 2010 and 13% in 2018 (trend P < .0001). The year 2014 was the breakpoint selected for segmented regression. Before 2014, the odds of PNB among the mastectomy cases was not significantly different from year to year. After 2014, the odds of PNB increased by 2.24-fold each year (95% confidence interval [CI], 2.00–2.49; P < .001); interaction test for pre-2014 versus post-2014 was P < .001. Similar trends were seen in the lumpectomy cases, where after 2014, the odds of PNB increased by 2.03-fold (95% CI, 1.81–2.27; P < .001); interaction test for pre-2014 versus post-2014 was P < .001. In the mastectomy cohort, year of procedure ≥2014, female sex, facility region, and tissue expander use were associated with higher odds of PNB. For lumpectomy cases, year of procedure ≥2014 and facility region were associated with higher odds of PNB use.

CONCLUSIONS:

We found increased annual utilization of PNB for mastectomy and lumpectomy since 2010, although absolute prevalence is low. PNB use was associated with year of procedure for both lumpectomy and mastectomy, particularly post-2014.
Free Hemoglobin Ratio as a Novel Biomarker of Acute Kidney Injury After On-Pump Cardiac Surgery: Secondary Analysis of a Randomized Controlled Trial
Authors: Hu Jie , Rezoagli Emanuele , Zadek Francesco , Bittner Edward A. , Lei Chong , Berra Lorenzo
Published: January 2021

BACKGROUND:

Cardiac surgery with cardiopulmonary bypass (CPB) is associated with a high risk of postoperative acute kidney injury (AKI). Due to limitations of current diagnostic strategies, we sought to determine whether free hemoglobin (fHb) ratio (ie, levels of fHb at the end of CPB divided by baseline fHb) could predict AKI after on-pump cardiac surgery.

METHODS:

This is a secondary analysis of a randomized controlled trial comparing the effect of nitric oxide (intervention) versus nitrogen (control) on AKI after cardiac surgery (NCT01802619). A total of 110 adult patients in the control arm were included. First, we determined whether fHb ratio was associated with AKI via multivariable analysis. Second, we verified whether fHb ratio could predict AKI and incorporation of fHb ratio could improve predictive performance at an early stage, compared with prediction using urinary biomarkers alone. We conducted restricted cubic spline in logistic regression for model development. We determined the predictive performance, including area under the receiver-operating-characteristics curve (AUC) and calibration (calibration plot and accuracy, ie, number of correct predictions divided by total number of predictions). We also used AUC test, likelihood ratio test, and net reclassification index (NRI) to compare the predictive performance between competing models (ie, fHb ratio versus neutrophil gelatinase–associated lipocalin [NGAL], N-acetyl-β-d-glucosaminidase [NAG], and kidney injury molecule-1 [KIM-1], respectively, and incorporation of fHb ratio with NGAL, NAG, and KIM-1 versus urinary biomarkers alone), if applicable.

RESULTS:

Data stratified by median fHb ratio showed that subjects with an fHb ratio >2.23 presented higher incidence of AKI (80.0% vs 49.1%; P = .001), more need of renal replacement therapy (10.9% vs 0%; P = .036), and higher in-hospital mortality (10.9% vs 0%; P = .036) than subjects with an fHb ratio ≤2.23. fHb ratio was associated with AKI after adjustment for preestablished factors. fHb ratio outperformed urinary biomarkers with the highest AUC of 0.704 (95% confidence interval [CI], 0.592-0.804) and accuracy of 0.714 (95% CI, 0.579-0.804). Incorporation of fHb ratio achieved better discrimination (AUC test, P = .012), calibration (likelihood ratio test, P < .001; accuracy, 0.740 [95% CI, 0.617-0.832] vs 0.632 [95% CI, 0.477-0.748]), and significant prediction increment (NRI, 0.638; 95% CI, 0.269-1.008; P < .001) at an early stage, compared with prediction using urinary biomarkers alone.

CONCLUSIONS:

Results from this exploratory, hypothesis-generating retrospective, observational study shows that fHb ratio at the end of CPB might be used as a novel, widely applicable biomarker for AKI. The use of fHb ratio might help for an early detection of AKI, compared with prediction based only on urinary biomarkers.