bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of Mortality in Patients of COVID-19 Pneumonia in Intensive Care Unit: An Observational Study in a Tertiary Care Hospital, Lucknow, India
Authors: Kumar Hemant , Gupta Preeti , Shakya Shobhit , Dixit Sumeet , Pandey Manoj Kumar , Gupta Nikhil , Pandey Amiya
Published: November 2021

Introduction: Coronavirus Disease-2019 (COVID-19) is caused by the Severe Acute Respiratory Coronavirus-2 (SARS-CoV-2) which is an enveloped positive-sense single-stranded RNA virus. Initial steps of the infection involve binding of the spike protein (S) of the virus to Angiotensin Converting Enzyme-2 (ACE-2) receptor on the mucosal surfaces of various organs like lungs, kidney, heart, intestine. Pathogenesis of complications are still poorly understood. Aim: This study was designed to find out the baseline biochemical parameters at the time of admission which may predict outcome in COVID-19 patients. Materials and Methods: This observational study was conducted in a dedicated COVID-19 hospital, Dr. Ram Manohar Lohia Institute of Medical Sciences (Dr. RMLIMS), Lucknow, Uttar Pradesh, India, from 1st July, 2020 to 30th November, 2020. A total of 109 moderate to severe COVID-19 pneumonia patients who required Intensive Care Unit (ICU) admission, were enrolled. Based on their outcome, patients were divided into two groups: “Survived” and “Expired”. Biochemical characteristics of patients were compared among the two groups using univariate and multivariate analysis. Results: On Univariate analysis Coagulation profile, Prothrombin Time (PT), International Normalised Ratio (INR), Activated Partial Thromboplastin Time (APTT) and D-Dimer values were raised significantly in the expired group. Among other acute phase reactants Lactate Dehydrogenase (LDH), C-Reactive Protein (CRP), Interleukin-6 (IL-6), and Creatinine Phosphokinase-MB (CPKMB) were raised in expired group and this difference was significant statistically too. On Multivariate analysis among all acute phase reactant only IL-6 was increased significantly. All other variables were found to be non significantly associated with mortality, statistically (p-value <0.05). Conclusion: Baseline biochemical parameters have prognostic values in COVID-19 patients. Raised IL-6 levels can be viewed as an independent predictor of mortality among COVID-19 patients at the time of admission in ICU.
Prevalence and Involvement of Different Valves in Rheumatic Heart Disease- An Observational Echocardiographic Study in a Tertiary Care Centre, Bengaluru, India
Authors: Lalitha S , Sai Vijay , Pasam Prajith , Bhargavi V
Published: November 2021

Introduction: Rheumatic Heart Disease (RHD) is a non suppurative sequelae of group A beta haemolytic streptococci, resulting from inadequately treated streptococcal sore throat or scarlet fever and leading to valvular heart disease. Rheumatic heart disease is a major cause of morbidity and mortality in younger population in developing countries. The present study was done at a tertiary care medical college hospital with the objective of establishing prevalence and involvement of different valve patterns by Echocardiography (ECHO). Aim: To analyse the valvular pattern of RHD over a period of four years in a tertiary care centre and highlight the importance of ECHO in the definitive diagnosis of RHD, and to know the continuing burden of RHD. Materials and Methods: This was a hospital based retrospective observational study conducted at Vydehi Institute of Medical Sciences and Research Centre, Bengaluru, Karnataka, India. A total of 518 cases of RHD were selected as a study population among the ECHO performed between January 2016 and January 2020 after an exclusion criterion of degenerative mitral and aortic valve disease, congenital aortic and mitral valve disease, myxomatous mitral valve disease, trivial and functional regurgitation. Analysis of valvular pattern was performed. Data analysis was done by tables, charts, percentages and ratio. Results: A total of 518 patients were diagnosed to have RHD by 2-Dimensional ECHO. Among them 276 (53%) were females and 242 (47%) were males. The average age was 41.9 years. The most common valve involved independently and in combined lesions was the mitral valve. Of the study population, 446 patients had Mitral Stenosis (MS) and 393 had Mitral Regurgitation (MR). Aortic Stenosis (AS) was found among 111 patients and 304 patients had Aortic Regurgitation (AR). Tricuspid Stenosis (TS) (organic) was found in seven cases. Multiple valves were involved in 204 cases. Among them 104 of the cases had MS, MR and AR, 69 cases had MS, MR, AS and AR, 21 cases had MS, AS and AR, seven cases had MR, AS and AR and three cases had MS, AS, AR and TS. Though aortic valve was involved in multi valvular lesions, significant AR (moderate and severe) was seen in 109 patients and significant AS (moderate and severe) was seen in 67 patients. Conclusion: RHD continues to be a major burden to population in developing countries. In the present study, various patterns of valvular involvement were noted. Drastic measures are to be taken primary and secondary prevention of RHD.
Can the 12-Lead Electrocardiogram Predict Myocardial Viability?
Authors: Anandaraj Arpudh Michael , Varghese Lijo , Krupa Jesu , Chacko Binita Riya , Irodi Aparna , Vimala Leena Robinson , George Oommen Kattunilam
Published: November 2021

Introduction: In patients with coronary artery disease and left ventricular dysfunction, the assessment of myocardial viability, prior to revascularisation has been shown to be of significant benefit. Most methods to assess myocardial viability such as Positron Emission Tomography (PET) and Cardiac MRI (CMR) are not readily available in resource constrained settings. The present study sought to determine if an easily available and inexpensive tool, such as the 12-lead surface Electrocardiogram (ECG) can be used as a screening tool to assess for myocardial viability. It is hypothesised that the R wave height as a marker of electrical activity would correlate with viability. Aim: To determine if the surface ECG can be used to predict myocardial viability. Materials and Methods: This retrospective study was conducted at the Christian Medical College and Hospital, Vellore, Tamil Nadu, India. Among all patients who had undergone CMR viability assessment as part of their routine care between February 2008 and October 2017, and analysis and preliminary write up was done between November 2017 and Decemeber 2018, 119 patients with previous anterior wall myocardial infarctions were identified. The 12-Lead ECGs of these patients were assessed for the height of R wave in lead V3 and sum of R wave heights in all precordial leads. Myocardial viability was assessed based on the extent of Late Gadolinium Enhancement (LGE) on CMR. Measures of diagnostic accuracy including sensitivity, specificity, predictive values and likelihood ratios were calculated. Results: It was found that a R wave height of less than 3 mm in lead V3 was 90.3% sensitive for the detection of non viable myocardium. Similarly, when the sum of the R wave heights in all precordial leads was less than 28.5 mm, it was 93.2% sensitive for the detection of non viable myocardium. Conclusion: In patients with previous anterior wall myocardial infarctions when the R wave height was less than 3 mm in lead V3, it was 90.3 % sensitive to identify those with non viable Left Anterior Descending artery (LAD) territory. The 12-Lead ECG is therefore a sensitive, inexpensive and easily available screening test to assess for LAD territory non viability.
Thermochromic Microcapsules Containing Chiral Mesogens Enclosed by Hydrogel Shell for Colorimetric Temperature Reporters
Authors: Kim Ji‐Won , Oh Yoonjin , Lee Sangmin , Kim Shin‐Hyun
Published: November 2021

Chiral mesogens spontaneously form a cholesteric phase and show structural colors through wavelength‐selective reflection. Although chiral mesogens are pragmatic materials to build cholesteric phase due to their low toxicity, low cost, and robustness, an elaborate encapsulation technique is not reported yet. In this work, cholesteryl esters are encapsulated with a calcium‐alginate hydrogel shell using oil‐in‐water‐in‐oil double‐emulsion droplets. With capillary microfluidic devices, monodisperse double‐emulsion droplets are prepared to have a mixture of cholesteryl ester and toluene in the innermost droplets and an aqueous solution of sodium alginate and calcium‐carrying complex in the outer droplets. As toluene diffuses out from the core, cholesteryl ester forms the cholesteric phase. At the same time, calcium ions are dissociated from the complex upon chemical cues, which causes ionic crosslinking of alginate. The microcapsules show the thermochromic property as the structural color of the cholesteric core blue‐shifts along with the temperature. Therefore, the microcapsules report local temperatures with colors or reflectance spectra. As the range and sensitivity of the colorimetric temperature measurement are controllable by adjusting the composition of cholesteryl esters, a wide range of temperature can be covered by employing a proper set of compositions while maintaining high sensitivity.
Tuning Electronic and Morphological Properties for High‐Performance Wavelength‐Selective Organic Near‐Infrared Cavity Photodetectors
Authors: Vanderspikken Jochen , Liu Quan , Liu Zhen , Vandermeeren Tom , Cardeynaels Tom , Gielen Sam , Van Mele Bruno , Van den Brande Niko , Champagne Benoît , Vandewal Koen , Maes Wouter
Published: November 2021

Incorporation of compact spectroscopic near‐infrared (NIR) light detectors into various wearable and handheld devices opens up new applications, such as on‐the‐spot medical diagnostics. To extend beyond the detection window of silicon, i.e., past 1000 nm, organic semiconductors are highly attractive because of their tunable absorption. In particular, organic NIR wavelength‐selective detectors have been realized by incorporating donor:acceptor thin films, exhibiting weak intermolecular charge‐transfer (CT) absorption, into an optical microcavity architecture. In this work, the alkyl side chains of the well‐known PBTTT donor polymer are replaced by alkoxy substituents, hereby redshifting the CT absorption of the polymer:PC61BM blend. It is shown that the unique fullerene intercalation features of the PBTTT polymer are retained when half of the side chains are altered, hereby maximizing the polymer:fullerene interfacial area and thus the CT absorption strength. This is exploited to extend the detection range of organic narrow‐band photodetectors with a full‐width‐at‐half‐maximum of 30–38 nm to wavelengths between 840 and 1340 nm, yielding detectivities in the range of 5 × 1011 to 1.75 × 1010 Jones, despite the low CT state energy of 0.98 eV. The broad wavelength tuning range achieved using a single polymer:fullerene blend renders this system an ideal candidate for miniature NIR spectrophotometers.
Regulation of Inflammatory Response and Osteogenesis to Citrate‐Based Biomaterials through Incorporation of Alkaline Fragments
Authors: Mao Lijie , Yin Yanrong , Zhang Lixin , Chen Xiaolei , Wang Xinqing , Chen Fangping , Liu Changsheng
Published: November 2021

A proper pH microenvironment is crucial to mobilizing regeneration function of biomaterials. Neutralizing the acidity in bone defects with alkaline substances is a promising strategy to create favorable environments for cell proliferation and bone repair. In this study, to neutralize the acidity and reduce the inflammation caused by the rapid release of citric acid, a novel citrate‐based biodegradable elastomeric poly(citric acid‐1,8‐octanediol–1,4‐bis(2‐hydroxyethyl)piperazine (BHEp)) (POPC) is synthesized with the introduction of the alkaline fragment BHEp, and then POPC/β‐tricalcium phosphate (β‐TCP) porous scaffolds are fabricated by 3D printing technique. The results reveal that the alkaline fragment BHEp effectively corrects the acid environment and improves the biocompatibility, cells affinity and promoted cell adhesion, and proliferation of POPC. Furthermore, the improved pH of POPC15/β‐TCP (PTCP15) enhances the adhesion and the proliferation of rabbit bone marrow mesenchymal stem cells, and the expression of osteogenesis‐related genes. Moreover, PTCP15 scaffolds relieve inflammatory response and switch RAW 264.7 toward a prohealing extreme. The rat femoral defect model further demonstrates good biocompatibility and enhanced bone regeneration of PTCP15. In conclusion, the results offer a promising approach for biodegradable polymers to address the degradation acidity issue. Meanwhile, a positive regulation strategy is provided for biopolymer to enhance cell proliferation, osteogenic differentiation, and bone repair.
Interpreting the Time‐Resolved Photoluminescence of Quasi‐2D Perovskites
Authors: Kaiser Milian , Li Yang , Allegro Isabel , Richards Bryce S. , Paetzold Ulrich Wilhelm , Howard Ian A.
Published: November 2021

Optical excitation of quasi‐2D perovskites leads to excited‐state populations of excitons, free charge carriers, or a mixture of both, depending on the type and amount of 2D spacer used. The fluence dependence of three quantities: 1) the time‐resolved photoluminescence decay, 2) the photoluminescence quantum yield (PLQY) after pulsed excitation, and 3) the initial rate of photon emission, allow the mixture of excited states present to be determined. These can be described by a simple model considering noninteracting populations of excitons and charge carriers in separate subvolumes of the film. The model reproduces all unique features of the data, such as the anomalous peak of the PLQY at intermediate fluences, due to bimolecular free carrier emission gaining efficiency before exciton–exciton annihilation reduces the exciton emission efficiency. The excited state population varies from 100% excitons in films made from high concentrations of butylamine spacers to ≈7% excitons and 93% free carriers for low concentrations of 1‐naphthylmethylamine spacers. The effective rates of free carrier recombination and exciton–exciton annihilation are high, often on the order of 1 × 10−9 cm3 s−1. The implications for the different excited‐state populations and their dynamics in terms of device engineering are discussed.
Interrupted CuAAC‐Thiolation for the Construction of 1,2,3‐Triazole‐Fused Eight‐Membered Heterocycles from O‐/N‐Propargyl derived Benzyl Thiosulfonates with Organic Azides
Authors: Jannapu Reddy Raju , Waheed Md. , Haritha Kumari Arram , Rama Krishna Gamidi
Published: November 2021

A copper(I)‐catalyzed interrupted click‐sulfenylation of O‐/N‐propargyl benzyl thiosulfonates with organic azides has been disclosed. The unified CuAAC‐thiolation provides a wide range of triazole‐fused eight‐membered heterocycles in good to high (51–94%) yields under mild reaction conditions. Moreover, a three‐component reaction is also achieved involving O‐/N‐propargyl benzyl thiosulfonates, benzyl bromide, and sodium azide to deliver fused‐triazoles in 61–74% yields. From a synthetic point of view, the present protocol has been demonstrated at gram‐scale reactions. A plausible mechanism is also proposed based on experimental results and control experiments.

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Cutaneous squamous cell carcinoma staging may influence management in users: A survey study
Authors: Patel Vishal A. , McCullum Catherine , Sparks Andrew D. , Schmults Chrysalyne D. , Arron Sarah T , Jambusaria‐Pahlajani Anokhi
Published: November 2021

Purpose

This study aims to determine whether there is consensus regarding staging and management of cutaneous squamous cell carcinoma (CSCC) across the various specialties that manage this disease.

Materials and Methods

A survey regarding CSCC high‐risk features, staging, and management was created and emailed to cutaneous oncology experts including dermatology, head and neck surgery/surgical oncology, radiation oncology, and medical oncology.

Results

One hundred fifty‐six (46%) of 357 invited physicians completed the survey. Depth of invasion (92%), perineural invasion (99%), histologic differentiation (85%), and patient immunosuppression (90%) achieved consensus (>80%) as high‐risk features of CSCC. Dermatologists were more likely to also choose clinical tumor diameter (79% vs. 54%) and histology (99% vs. 66%) as a high‐risk feature. Dermatologists were also more likely to utilize the Brigham and Women's Hospital (BWH) staging system alone or in conjunction with American Joint Committee on Cancer (AJCC) (71%), whereas other cancer specialists (OCS) tend to use only AJCC (71%). Respondents considered AJCC T3 and higher (90%) and BWH T2b and higher (100%) to be high risk and when they consider radiologic imaging, sentinel lymph node biopsy, post‐operative radiation therapy, and increased follow‐up. Notably, a large number of respondents do not use staging systems or tumor stage to determine treatment options beyond surgery in high‐risk CSCC.

Conclusion

This survey study highlights areas of consensus and differences regarding the definition of high‐risk features of CSCC, staging approaches, and management patterns between dermatologists and OCS. High‐risk CSCC is defined as, but not limited to, BWH T2b and higher and AJCC T3 and higher, and these thresholds can be used to identify cases for which treatment beyond surgery may be considered. Dermatologists are more likely to utilize BWH staging, likely because BWH validation studies showing advantages over AJCC were published in dermatology journals and discussed at dermatology meetings. Additional data are necessary to develop a comprehensive risk‐based management approach for CSCC.
Priapism as the first manifestation in chronic myeloid leukemia: A case report and focused review of literature
Authors: Sossa Melo Claudia Lucia , Orozco Orozco Carlos Alberto , Peña Castellanos Angela Maria , Rueda Perea Maria Alejandra , Porras Bueno Cristian Orlando , Romero Diaz Carlos Ivan , Rojas Rodríguez Helga Natalia
Published: November 2021

We report the case of a patient who was initially presented with ischemic priapism to the emergency department. He was treated with adrenaline intracavernous injections and aspiration with irrigation of the corpora cavernosa and distal shunt. In the postoperative period, anemia, basophilia, eosinophilia, thrombocytosis and hyperleukocytosis were detected. The patient was subsequently diagnosed with chronic myeloid leukemia.

Priapism is a rare manifestation of chronic myeloid leukemia (≤ 3%) and occurs mostly due to hyperleukocytosis, resulting in thrombus formation and corporal venous outflow obstruction. Priapism occurring in any setting is considered as a medical emergency that requires immediate local therapy because of resulting irreversible cell damage and fibrosis if not treated within the first 24–48 h.
Bilateral cataract surgery in a Japanese macaque (Macaca fuscata): A case report
Authors: Miwa Yukihiro , Komatsu Hiroyuki , Shinojima Ari , Oda Ayako , Inagaki Mao , Usami Kensuke , Akasaka Minori , Kobayashi Yoshitaka
Published: November 2021

A 7.5‐year‐old intact male Japanese macaque was presented for evaluation of vision loss. After a complete ophthalmic examination, the patient was diagnosed with hypermature cataract in both eyes. After the cataract surgery, it was able to locate food and walk in a straight line.
Continuous infusion of piperacillin‐tazobactam significantly improves target attainment in children with cancer and fever
Authors: Maarbjerg Sabine F. , Thorsted Anders , Friberg Lena E. , Nielsen Elisabet I. , Wang Mikala , Schrøder Henrik , Albertsen Birgitte K.
Published: November 2021

Background

Children with febrile neutropenia commonly exhibit alterations of pharmacokinetic (PK) parameters, leading to decreased β‐lactam concentrations.

Aims

This study evaluated piperacillin PK and probability of target attainment (PTA) with continuous infusion of piperacillin‐tazobactam, in order to optimize the dosing regimen.

Methods

This prospective PK study included children with cancer, aged 1–17 years, who were treated with piperacillin‐tazobactam for suspected or verified infection. A piperacillin‐tazobactam loading dose (100 mg/kg) was administered followed by continuous infusion (300 mg/kg/day). The unbound fraction of piperacillin was quantified by high‐performance liquid chromatography and PK were described using population PK modeling. PK data was used to update and extend a previous PK model built on data following intermittent administration. Monte Carlo simulations were performed to assess PTA for targets of 100% time above the minimum inhibitory concentration (100% fT > MIC) and 50% fT > 4xMIC.

Results

We included 68 fever episodes among 38 children with a median (IQR) age of 6.5 years and body weight of 27.4 kg (15.1–54.0). A three‐compartment model adequately described the concentration‐time data. Median (95% confidence interval) estimates for clearance and piperacillin concentration at steady state were 14.2 L/h/70 kg (13.0; 15.3) and 47.6 mg/L (17.2; 129.5), respectively. Body weight or lean body weight was significantly associated with the PK parameters, and body weight was integrated in the final PK model. Based on piperacillin exposure, continuous infusion was the only dosing regimen to achieve optimal PTA for the P. aeruginosa breakpoint (16 mg/L) with the target of 100% fT > MIC, and a daily dose of 300 mg/kg reached optimal PTA. The strict target of 50% fT > 4xMIC (64 mg/L) was not feasibly attained by any dosing regimen at recommended doses.

Conclusion

Unlike conventional piperacillin intermittent administration and extended infusion regimens, continuous infusion allows the target of 100% fT > MIC to be reached for children with febrile neutropenia.
The impact of the use of the ACR‐TIRADS as a screening tool for thyroid nodules in a cancer center
Authors: Araruna Bezerra de Melo Rayssa , Menis Fabio , Calsavara Vinicus Fernando , Stefanini Flavio Scavone , Novaes Tullio , Saieg Mauro
Published: November 2021

Background

The Thyroid Imaging Reporting and Data System (TIRADS) was created to assess risk of thyroid nodules through ultrasound. Plenty classifications methods for thyroid nodules have already been created, but none of them have yet achieved global utilization. This study analyzed the performance of the American College of Radiology (ACR) TIRADS, its reproducibility and the impact of its utilization as a screening method in a large Cancer Center cohort.

Methods

Thyroid nodules which underwent fine‐needle aspiration (FNA) in a 1‐year period were selected, with their ultrasound images retrospectively classified according to the ACR TI‐RADS. Cytological evaluation of the nodules and final histology (whenever available) was used to assess risk of neoplasm (RON) and risk of malignancy (ROM) associated to each ACR‐TIRADS category. Further analyses were also carried out according to recommendation or not of FNA by the ACR‐TIRADS and nodule size. Inter‐observer agreement for the system was also assessed.

Results

A total of 1112 thyroid nodules were included. RON for each category according to final cytological diagnosis was 0% for TR1 and TR2, 2.1% for TR3; 15.6% for TR4 and 68.9% for TR5. No significant difference was observed between the RON of the categories for cases above or below 1.0 cm. Nodules that met the criteria for FNA had 3 times greater chance of a positive outcome. Substantial agreement (kappa 0.77) was seen between two different observers.

Conclusions

ACR TI‐RADS scoring system has demonstrated to be an accurate method to stratify thyroid nodules in a Cancer Center, with a high reproducibility.
The likelihood of severe COVID‐19 outcomes among PLHIV with various comorbidities: a comparative frequentist and Bayesian meta‐analysis approach
Authors: Wang Haoyi , Jonas Kai J.
Published: November 2021

Introduction

The SARS‐CoV‐2 virus can currently pose a serious health threat and can lead to severe COVID‐19 outcomes, especially for populations suffering from comorbidities. Currently, the data available on the risk for severe COVID‐19 outcomes due to an HIV infection with or without comorbidities paint a heterogenous picture. In this meta‐analysis, we summarized the likelihood for severe COVID‐19 outcomes among people living with HIV (PLHIV) with or without comorbidities.

Methods

Following PRISMA guidelines, we utilized PubMed, Web of Science and medRxiv to search for studies describing COVID‐19 outcomes in PLHIV with or without comorbidities up to 25 June 2021. Consequently, we conducted two meta‐analyses, based on a classic frequentist and Bayesian perspective of higher quality studies.

Results and discussion

We identified 2580 studies (search period: January 2020–25 June 2021, data extraction period: 1 January 2021–25 June 2021) and included nine in the meta‐analysis. Based on the frequentist meta‐analytical model, PLHIV with diabetes had a seven times higher risk of severe COVID‐19 outcomes (odd ratio, OR = 6.69, 95% CI: 3.03–19.30), PLHIV with hypertension a four times higher risk (OR = 4.14, 95% CI: 2.12–8.17), PLHIV with cardiovascular disease an odds ratio of 4.75 (95% CI: 1.89–11.94), PLHIV with respiratory disease an odds ratio of 3.67 (95% CI: 1.79–7.54) and PLHIV with chronic kidney disease an OR of 9.02 (95% CI: 2.53–32.14) compared to PLHIV without comorbidities. Both meta‐analytic models converged, thereby providing robust summative evidence. The Bayesian meta‐analysis produced similar effects overall, with the exclusion of PLHIV with respiratory diseases who showed a non‐significant higher risk to develop severe COVID‐19 outcomes compared to PLHIV without comorbidities.

Conclusions

Our meta‐analyses show that people with HIV, PLHIV with coexisting diabetes, hypertension, cardiovascular disease, respiratory disease and chronic kidney disease are at a higher likelihood of developing severe COVID‐19 outcomes. Bayesian analysis helped to estimate small sample biases and provided predictive likelihoods. Clinical practice should take these risks due to comorbidities into account and not only focus on the HIV status alone, vaccination priorities should be adjusted accordingly.
The relationship between knee loading during gait and cartilage thickness in nontraumatic and posttraumatic knee osteoarthritis
Authors: Teoli Anthony , Cloutier‐Gendron Melissa , Ho Shirley Y. K. , Gu Susan , Pelletier Jean‐Pierre , Martel‐Pelletier Johanne , Robbins Shawn M.
Published: November 2021

The relationship between knee moments and markers of knee osteoarthritis progression has not been examined in different knee osteoarthritis subtypes. The objective was to examine relationships between external knee moments during gait and tibiofemoral cartilage thickness in patients with nontraumatic and posttraumatic knee osteoarthritis. For this cross‐sectional study, participants with knee osteoarthritis were classified into two groups: nontraumatic (n = 22; mean age 60 years) and posttraumatic (n = 19; mean age 56 years, history of anterior cruciate ligament rupture). Gait data were collected with a three‐dimensional motion capture system sampled at 100 Hz and force plates sampled at 2000 Hz. External knee moments were calculated using inverse dynamics. Cartilage thickness was determined with magnetic resonance imaging (T1‐weighted, 3D sagittal gradient‐echo sequence). Linear regression analyses examined relationships between cartilage thickness with knee moments, group, and their interaction. A higher knee adduction moment impulse was negatively associated with medial to lateral cartilage thickness ratio (B = −1.97). This relationship differed between participants in the nontraumatic osteoarthritis group (r = −0.56) and posttraumatic osteoarthritis group (r = −0.30). A higher late stance knee extension moment was associated with greater medial femoral condyle cartilage thickness (B = −0.86) and medial to lateral cartilage thickness (B = −0.73). These relationships also differed between participants in the nontraumatic osteoarthritis group (r = −0.61 and r = −0.51, respectively) and posttraumatic osteoarthritis group (r = 0.10 and r = 0.25, respectively). Clinical Significance: The relationship between knee moments with tibiofemoral cartilage thickness differs between patients with nontraumatic and posttraumatic knee osteoarthritis. The potential influence of mechanical knee loading on articular cartilage may also differ between these subtypes.
Using attenuated‐total‐reflection Fourier‐transformed spectroscopy to reveal molecular structural differences among willow (Salix spp.) foliage cultivars in relation to their potential as fodders
Authors: Ortuño Jordi , Traynor Thomas , Campbell Mairead , Theodoridou Katerina
Published: November 2021

BACKGROUND

Willow trees represent a suitable species for the development of agroforestry systems, integrating bioenergy and animal feed production. However, there is a lack of information regarding the suitability of leaves and stems, considered a bioenergy by‐product, as animal feed. The aim of this study was the employment of attenuated total reflectance Fourier transform infrared spectroscopy (550–4000 cm−1) to investigate differences in the nutrient molecular structure profile of leaves and stems of selected willow cultivars to understand their utility for ruminant nutrition.

RESULTS

Univariate analysis of variance of leaves showed lower intensities of cellulosic compounds and higher of protein in comparison with stems, which suggests higher leaf dry matter and protein digestibility. Spectral analyses revealed differences in both plant parts between Salix cv. Terra Nova and Salix cv. Beagle, cv. Resolution, and cv. Olof. The higher α‐helix to β‐sheet ratio, which is related to a higher protein digestibility, was in correlation with the lower content of condensed tannins. Principal component and agglomerative hierarchical cluster analyses showed significant discrimination among willow cultivars in the cellulosic, structural carbohydrate, and amide regions, whereas differences were less evident for total carbohydrate and lipid‐related regions.

CONCLUSION

The application of attenuated total reflectance Fourier transform infrared molecular spectroscopy is an effective tool to rapidly identify spectral features related to the nutritional composition of willow foliage and to discriminate between cultivars and parts of the plant. This information would be useful to optimize the use of willow fodders in agroforestry systems. © 2021 Society of Chemical Industry.
Multitime point pepsin testing can double the rate of the diagnosis of laryngopharyngeal reflux
Authors: Zhang Jinhong , Li Jinrang , Zhang Yanping , Nie Qian , Zhang Ran , Wang Xiaoyu , Jiang Xingwang , Wu Yingying , Wu Runze , Bi Xinxin , Cui Xiaohuan , Song Hui , Ran Taotao , Li Lina
Published: November 2021

Objective

To study the value of multitime point salivary pepsin testing (MTPSPT) for the diagnosis of laryngopharyngeal reflux (LPR).

Study Design

Prospective noncontrolled.

Methods

For patients who met the enrollment criteria, the reflux symptom index (RSI) and reflux finding score (RFS) were calculated and salivary pepsin testing was performed. The pepsin test was performed every hour from 7:00 a.m. to 6:00 p.m. by collecting fresh saliva samples. A single positive test result was needed for the diagnosis of LPR. The consistency in the diagnosis of LPR between the two methods was compared with the weighted Cohen's kappa statistic.

Results

A total of 204 patients were included. The kappa value between the two methods was 0.566 (p = .00). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MTPSPT were 76.43%, 85.94%, 92.24%, and 62.5%, respectively. We also compared a single pepsin measure at 7 a.m. with the screening results based on the RSI and RFS, and found a much lower kappa agreement value (0.223, p = .00). The sensitivity, specificity, PPV, NPV, and false‐negative rate of pepsin testing at 7 a.m. (fasting) were 37.86%, 92.18%, 91.38%, 40.41%, and 58.57%, respectively.

Conclusion

The use of the result of a single salivary pepsin test in the morning yields a relatively higher rate of missed diagnosis of LPR, and multitime point testing through a day increased the accuracy and sensitivity of detection of LPR twofold compared to a single morning fasting sample.

Level of Evidence

3
Antioxidative and Anti‐UV Lignin Carrier for Peptide Delivery
Authors: Chee Pei Lin , Sugiarto Sigit , Yu Yong , Tan Ying Chuan , Ye Enyi , Kai Dan , Loh Xian Jun
Published: November 2021

Here, a sustainable antioxidant carrier based on lignin is developed to deliver palmitoyl tripeptide‐38. The poly(lignin/polyethylene glycol (PEG)/polypropylene glycol (PPG) urethane) is polymerized by randomly coupling lignin, PEG and PPG segment blocks using hexamethylene diisocyanate as a crosslinker. The derived poly(lignin/PEG/PPG urethane) loaded with palmitoyl tripeptide‐38, referred to as LM, is designed with careful considerations of both intrinsic and extrinsic causes of skin aging and a two‐way approach is taken on to effectively target the problem of skin aging. Upon exposure to the ultraviolet irradiation, LM successfully protects the cells by reducing the presence of reactive oxygen species, the damage to the antioxidant enzymes, and the expression of MMP‐1. Concurrently, LM also promotes the collagen production for skin repair. It is noteworthy that the collagen I content, in cells exposed to ultraviolet irradiation with LM‐4 and LM‐8 treatment (LM with 4 and 8 µg mL−1 palmitoyl tripeptide‐38, respectively), exceeds that of the control. Overall, this work successfully demonstrates a sustainable carrier with good antioxidant properties that effectively assisted the uptake of palmitoyl tripeptide‐38 by the cells.
Rapid Eye Movement Sleep Behavior Disorder: Abnormal Cardiac Image and Progressive Abnormal Metabolic Brain Pattern
Authors: Janzen Annette , Kogan Rosalie V. , Meles Sanne K. , Sittig Elisabeth , Renken Remco J. , Geibl Fanni F. , Booij Jan , Stormezand Gilles , Luster Markus , Mayer Geert , Leenders Klaus L. , Oertel Wolfgang H.
Published: November 2021

Background

Isolated rapid eye movement sleep behavior disorder (iRBD) is prodromal for α‐synucleinopathies.

Objective

The aim of this study was to determine whether pathological cardiac [123I]meta‐iodobenzylguanidine scintigraphy ([123I]MIBG) is associated with progression of [18F]fluorodeoxyglucose‐positron emission tomography–based Parkinson's disease (PD)‐related brain pattern (PDRP) expression in iRBD.

Methods

Seventeen subjects with iRBD underwent [18F]fluorodeoxyglucose‐positron emission tomography brain imaging twice ~3.6 years apart. In addition, [123I]MIBG and [123I]N‐ω‐fluoropropyl‐2β‐carbomethoxy‐3β‐(4‐iodophenyl)nortropane single‐photon emission computed tomography ([123I]FP‐CIT‐SPECT) at baseline were performed. Olfactory, cognitive, and motor functions were tested annually.

Results

Twelve of 17 subjects had pathological [123I]MIBG. At baseline, 6 of 12 of these expressed the PDRP (suprathreshold PDRP z score). At follow‐up, 12 of 17 subjects had suprathreshold PDRP z scores, associated with pathological [123I]MIBG in 92% and with pathological [123I]FP‐CIT‐SPECT in 75%. Subjects with pathological [123I]MIBG had higher PDRP z score change per year (P = 0.027). Three subjects phenoconverted to PD; all had pathological [123I]MIBG and [123I]FP‐CIT‐SPECT, suprathreshold baseline PDRP z scores, and hyposmia.

Conclusions

Pathological [123I]MIBG was associated with progressive and suprathreshold PDRP z scores at follow‐up. Abnormal [123I]MIBG likely identifies iRBD as prodromal PD earlier than pathological [123I]FP‐CIT‐SPECT. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Global dynamics and traveling wave solutions for a three‐species model
Authors: Li Fanfan , Han Zhenlai , Yang Ting‐Hui
Published: November 2021

In this work, we investigate the system of a three‐species ecological model involving one predator–prey subsystem coupling with a generalist predator with negative effect on the prey. Without diffusive terms, all global dynamics of its corresponding reaction equations are proved analytically for all classified parameters. With diffusive terms, the transitions of different spatial homogeneous solutions, the existence of traveling wave solutions, are investigated by a higher dimensional shooting method, the Wazewski method. These mathematical results, under mild conditions, imply that a generalist predator can stabilize a predator–prey system even with negative effects of coupling. Finally, some biological implications are given and the interesting numerical simulations are performed.
A customizable anthropomorphic phantom for dosimetric verification of 3D‐printed lung, tissue, and bone density materials
Authors: Tino Rance Bolislis , Yeo Adam Unjin , Brandt Milan , Leary Martin , Kron Tomas
Published: November 2021

Purpose

To design and manufacture a customized thoracic phantom slab utilizing the 3D printing process, also known as additive manufacturing, consisting of different tissue density materials. Here, we demonstrate the 3D‐printed phantom's clinical feasibility for imaging and dosimetric verification of volumetric modulated arc radiotherapy (VMAT) plans for lung and spine stereotactic ablative body radiotherapy (SABR) through end‐to‐end dosimetric verification.

Methods

A customizable anthropomorphic phantom slab was designed using the CT dataset of a commercial phantom (adult female ATOM dosimetry phantom, CIRS Inc.). Material extrusion 3D printing was utilized to manufacture the phantom slab consisting of acrylonitrile butadiene styrene material for the lung and the associated lesion, polylactic acid (PLA) material for soft tissue and spinal cord, and both PLA and iron‐reinforced PLA materials for bone. CT images were acquired for both the commercial phantom and 3D‐printed phantom for HU comparison. VMAT plans were generated for spine and lung SABR scenarios and were delivered as per departmental SABR protocols using a Varian TrueBeam STx linear accelerator. End‐to‐end dosimetry was implemented with radiochromic films, analyzed with gamma criteria of 5% dose difference, and a distance‐to‐agreement of 1 mm, at a 10% low‐dose threshold by comparing with calculated dose using the Acuros algorithm of the Eclipse treatment planning system (v15.6).

Results

3D‐printed phantom inserts were observed to produce HU ranging from –750 to 2100. The 3D‐printed phantom slab was observed to achieve a similar range of HU from the commercial phantom including a mean HU of –760 for lung tissue, a mean HU of 50 for soft tissue, and a mean HU of 220 and 630 for low‐ and high‐density bone, respectively. Film dosimetry results show 2D‐gamma passing rates for lung SABR (internal and superior) and spine SABR (inferior and superior) over 98% and 90%, respectively.

Conclusions

The end‐to‐end testing of VMAT plans for spine and lung SABR suggests the clinical feasibility of the 3D‐printed phantom, consisting of different tissue density materials that emulate lung, soft tissue, and bone in kV imaging and megavoltage photon dosimetry. Further investigation of the proposed 3D printing techniques for manufacturability and reproducibility will enable the development of clinical 3D‐printed phantoms in radiotherapy.
Adiposity, related biomarkers, and type 2 diabetes after gestational diabetes: The Diabetes Prevention Program
Authors: Wander Pandora L. , Christophi Costas A. , Araneta Maria Rosario G. , Boyko Edward J. , Enquobahrie Daniel A. , Dabelea Dana , Goldberg Ronald B. , Kahn Steven E. , Kim Catherine , Pi‐Sunyer Xavier , Knowler William C.
Published: November 2021

Objective

This study investigated associations of adiposity and adiposity‐related biomarkers with incident type 2 diabetes (T2D) among parous women.

Methods

Among women in the Diabetes Prevention Program (DPP) who reported a previous live birth, circulating biomarkers (leptin, adiponectin, sex hormone‐binding globulin, and alanine aminotransferase;n= 1,711) were measured at enrollment (average: 12 years post partum). Visceral (VAT) and subcutaneous adipose tissue areas at the L2‐L3 region and the L3‐L4 region were quantified by computed tomography (n= 477). Overall and stratified (by history of gestational diabetes mellitus [GDM]) adjusted Cox proportional hazards models were fit.

Results

Alanine aminotransferase, L2‐L3 VAT, and L3‐L4 VAT were positively associated (hazard ratio [HR] for 1‐SD increases: 1.073,p= 0.024; 1.251,p= 0.009; 1.272,p= 0.004, respectively), and adiponectin concentration was inversely associated with T2D (HR 0.762,p< 0.001). Whereas leptin concentration was not associated with T2D overall, in GDM‐stratified models, a 1‐SD higher leptin was positively associated with risk of T2D in women without GDM (HR: 1.126,p= 0.016) and inversely in women with a history of GDM (HR: 0.776,p= 0.013, interactionp= 0.002).

Conclusions

Among parous women, alanine aminotransferase and VAT are positively associated with incident T2D, whereas adiponectin is inversely associated. Leptin is associated with higher risk of T2D in women with a history of GDM but a lower risk in women without a history of GDM.
Proteome‐wide associations with short‐ and long‐term weight loss and regain after Roux‐en‐Y gastric bypass surgery
Authors: Yousri Noha A. , Engelke Rudolf , Sarwath Hina , McKinlay Rodrick D. , Simper Steven C. , Adams Ted D. , Schmidt Frank , Suhre Karsten , Hunt Steven C.
Published: November 2021

Objective

Gastric bypass surgery results in long‐term weight loss. Small studies have examined protein changes during rapid weight loss (up to 1 or 2 years post surgery). This study tested whether short‐term changes were maintained after 12 years.

Methods

A 12‐year follow‐up, protein‐wide association study of 1,297 SomaLogic aptamer‐based plasma proteins compared short‐ (2‐year) and long‐term (12‐year) protein changes in 234 individuals who had gastric bypass surgery with 144 nonintervened individuals with severe obesity.

Results

There were 51 replicated 12‐year protein changes that differed between the surgery and nonsurgery groups. Adjusting for change in BMI, only 12 proteins remained significant, suggesting that BMI change was the primary reason for most protein changes and not non‐BMI‐related surgical effects. Protein changes were related to BMI changes during both weight‐loss and weight‐regain periods. The significant proteins were associated primarily with lipid, uric acid, or resting energy expenditure clinical variables and metabolic pathways. Eight protein changes were associated with 12‐year diabetes remission, including apolipoprotein M, sex hormone binding globulin, and adiponectin (p < 3.5 × 10−5).

Conclusions

This study showed that most short‐term postsurgical changes in proteins were maintained at 12 years. Systemic protection pathways, including inflammation, complement, lipid, and adipocyte pathways, were related to the long‐term benefits of gastric bypass surgery.
Role of tunable polymer flexibility in controlling wetting behavior and thermal properties of poly(1,3‐cyclohexadiene)‐silica nanocomposites
Authors: Bornani Kamlesh , Shah Priyank , Barkakaty Balaka , Chen Jihua , Lokitz Bradley , Mays Jimmy , Kilbey S. Michael
Published: November 2021

We present how altering the chain flexibility affects the nanoscale organization of polymer‐grafted nanoparticles (PGNPs) and its ultimate impact on macroscale thermal properties. To isolate the role of chain flexibility on wetting behavior in athermal polymer nanocomposites (PNC), the graft and matrix chemistry is kept identical by utilizing 1,3‐cyclohexadiene‐based polymer materials. Increasing the rigidity and molecular weight of both the graft and matrix is found to favor mixing of poly(1,3‐cyclohexadiene) PCHD‐grafted silica NPs with the matrix, supported by a concomitant increase in glass transition temperatures of the PNCs. Further, the associated entropic factors that drive wetting behavior and dispersion of PGNPs are discussed, emphasizing the dominant role‐played by chain flexibility. Alterations in graft flexibility had the strongest impact on dispersion and Tg values of the PNC, while molecular weight (MW) plays a secondary role. This investigation is a unique demonstration of how chain flexibility alteration in athermal semiflexible systems can be used to alter NP organization by altering filler‐matrix wettability which also impacts thermal properties.
Inhibition of bacterial FMN transferase: A potential avenue for countering antimicrobial resistance
Authors: Deka Ranjit K. , Deka Akanksha , Liu Wei Z. , Norgard Michael V. , Brautigam Chad A.
Published: November 2021

Antibiotic resistance is a challenge for the control of bacterial infections. In an effort to explore unconventional avenues for antibacterial drug development, we focused on the FMN‐transferase activity of the enzyme Ftp from the syphilis spirochete, Treponema pallidum (Ftp_Tp). This enzyme, which is only found in prokaryotes and trypanosomatids, post‐translationally modifies proteins in the periplasm, covalently linking FMN (from FAD) to proteins that typically are important for establishing an essential electrochemical gradient across the cytoplasmic membrane. As such, Ftp inhibitors potentially represent a new class of antimicrobials. Previously, we showed that AMP is both a product of the Ftp_tp‐catalyzed reaction and an inhibitor of the enzyme. As a preliminary step in exploiting this property to develop a novel Ftp_Tp inhibitor, we have used structural and solution studies to examine the inhibitory and enzyme‐binding properties of several adenine‐based nucleosides, with particular focus on the 2‐position of the purine ring. Implications for future drug design are discussed.
AutoRepar: A method to obtain identifiable and observable reparameterizations of dynamic models with mechanistic insights
Authors: Massonis Gemma , Banga Julio R. , Villaverde Alejandro F.
Published: November 2021

Mechanistic dynamic models of biological systems allow for a quantitative and systematic interpretation of data and the generation of testable hypotheses. However, these models are often over‐parameterized, leading to nonidentifiability and nonobservability, that is, the impossibility of inferring their parameters and state variables. The lack of structural identifiability and observability (SIO) compromises a model's ability to make predictions and provide insight. Here we present a methodology, AutoRepar, that corrects SIO deficiencies of nonlinear ODE models automatically, yielding reparameterized models that are structurally identifiable and observable. The reparameterization preserves the mechanistic meaning of selected variables, and has the exact same dynamics and input‐output mapping as the original model. We implement AutoRepar as an extension of the STRIKE‐GOLDD software toolbox for SIO analysis, applying it to several models from the literature to demonstrate its ability to repair their structural deficiencies. AutoRepar increases the applicability of mechanistic models, enabling them to provide reliable information about their parameters and dynamics.