bluuebunny/crossref_metadata_2025 huggingface dataset:
Three-body renormalization group limit cycles based on unsupervised feature learning
Authors: Kaspschak Bastian , Meißner Ulf-G
Published: February 2022

Both the three-body system and the inverse square potential carry a special significance in the study of renormalization group limit cycles. In this work, we pursue an exploratory approach and address the question which two-body interactions lead to limit cycles in the three-body system at low energies, without imposing any restrictions upon the scattering length. For this, we train a boosted ensemble of variational autoencoders, that not only provide a severe dimensionality reduction, but also allow to generate further synthetic potentials, which is an important prerequisite in order to efficiently search for limit cycles in low-dimensional latent space. We do so by applying an elitist genetic algorithm to a population of synthetic potentials that minimizes a specially defined limit-cycle-loss. The resulting fittest individuals suggest that the inverse square potential is the only two-body potential that minimizes this limit cycle loss independent of the hyperangle.
An Improved Unsegmented Phonocardiogram Classification Using Nonlinear Time Scattering Features
Authors: Ajitkumar Singh Sinam , Dinita Devi Ningthoujam , Majumder Swanirbhar
Published: February 2022

Phonocardiogram (PCG) signals highlight the relevant characteristics for the prediction of heart diseases or heart-related disorders. However, it is challenging to classify heart abnormality relying on an unbalanced PCG dataset due to low classification performance. Recently, several studies have attempted to predict heart abnormality based on segmented and unsegmented features extracted using PCG signals. This study aims to develop an automated PCG classification model eliminating any segmentation of the heart sound signal for predicting heart abnormality. So, we have proposed a new approach based on wavelet scattering transform to predict two classes of PCG signals, namely, normal and abnormal. Based on the wavelet scattering transform, five scattering time window features were extracted from each PCG signal. The PhysioNet 2016 PCG database has been used here to evaluate and compare the classification performance based on the k Nearest Neighbors (KNN) classifier. The proposed architecture used a KNN classifier with different distance functions (Euclidean, Cityblock, Chebyshev, Minkowsky, Correlation, Spearman and Cosine) and has been compared with other traditional classifiers (classification tree, linear discriminant analysis, support vector machine and ensemble). The proposed framework using nonlinear wavelet scattering features with a KNN classifier based Cityblock distance function achieved classification performance over the total datasets with accuracy, sensitivity and specificity values of 97.82%, 95.04% and 98.72%, respectively.
Approaches to management of rhabdomyolysis as the adverse effect of drug interaction between atorvastatin and sacubitril/valsartan: a case report
Authors: Siew Kelvin Shenq Woei , Abdul Hafidz Muhammad Imran , Mohd Zaidan Fatimah Zahrah Binti , Hadi Mohd Firdaus bin
Published: February 2022

Background

Atorvastatin and sacubitril/valsartan (Entresto™) have been cornerstones in managing patients with coronary artery disease and heart failure (HF). We report a case of life-threatening rhabdomyolysis associated with the co-administration of atorvastatin and sacubitril/valsartan.

Case summary

A 58-year-old male with coronary heart disease and chronic HF treated with the optimal dose of atorvastatin and other cardiovascular medications was frequently admitted for acute decompensation of HF. We decided to optimize his condition by adding sacubitril/valsartan to his treatment regime. He presented to our outpatient clinic with worsening myalgia and oliguria 6 days later. He was readmitted with markedly elevated serum creatinine kinase (CK) (94 850 U/L; normal range 32–294 U/L), deranged liver function tests, and acute kidney injury. We withheld atorvastatin and sacubitril/valsartan and treated him with renal replacement therapy.

Discussion

Sacubitril inhibits the excretion of statins, thereby elevating serum statin concentration and increasing the likelihood of developing muscle-related toxicity. Co-administration of atorvastatin and sacubitril/valsartan should be monitored closely with laboratory investigations of CK and liver and renal function. The physician may consider starting low-dose atorvastatin at 20 mg daily in combination with sacubitril/valsartan 24 mg/26 mg twice daily and titrating accordingly to optimal doses. Rosuvastatin could be an alternative to atorvastatin, as it has less drug–drug interaction with sacubitril, thereby reducing the adverse effect.
Accelerated 2.5-D inversion of airborne transient electromagnetic data using reduced 3-D meshing
Authors: Engebretsen Kim Wann , Zhang Bo , Fiandaca Gianluca , Madsen Line Meldgaard , Auken Esben , Christiansen Anders Vest
Published: February 2022

Airborne systems collecting transient electromagnetic data are able to gather large amounts of data over large areas in a very short time. These data are most often interpreted through 1-D inversions, due to the availability of robust, fast and efficient codes. However, in areas where the subsurface contains complex structures or large conductivity contrasts, 1-D inversions may introduce artefacts into the models, which may prevent correct interpretation of the results. In these cases, 2-D or 3-D inversion should be used. Here, we present a 2.5-D inversion code using 3-D forward modelling combined with a 2-D model grid. A 2.5-D inversion is useful where the flight lines are spaced far apart, in which case a 3-D inversion would not add value in relation to the added computational cost and complexity. By exploiting the symmetry of the transmitter and receiver system we are able to perform forward calculations on a reduced 3-D mesh using only half the domain transecting the centre of the transmitter and receiver system. The forward responses and sensitivities from the reduced 3-D mesh are projected onto a structured 2-D model grid following the flight direction. The difference in forward calculations is within 1.4 per cent using the reduced mesh compared to a full 3-D solution. The inversion code is tested on a synthetic example constructed with complex geology and high conductivity contrasts and the results are compared to a 1-D inversion. We find that the 2.5-D inversion recovers both the conductivity values and shape of the true model with a significantly higher accuracy than the 1-D inversion. Finally, the results are supported by a field case using airborne TEM data from the island of Mayotte. The inverted flight line consisted of 418 soundings, and the inversion spent an average of 6750 s per iteration, converging in 16 iterations with a peak memory usage of 97 GB, using 18 logical processors. In general, the total time of the 2-D inversions compared to a full 3-D inversion is reduced by a factor of 2.5 while the memory consumption was reduced by a factor of 2, reflecting the half-mesh approach.
Multisegment ruptures andVp/Vsvariations during the 2020–2021 seismic crisis in western Corinth Gulf, Greece
Authors: Mesimeri Maria , Ganas Athanassios , Pankow Kristine L
Published: February 2022

On 2020 December 23, a seismic crisis initiated in the western Corinth Gulf offshore Marathias, lasted several months, and generated thousands of small magnitude earthquakes. The Gulf of Corinth is well known for earthquake swarm occurrence and short-lived burst-like earthquake sequences, mostly triggered by crustal fluids. Here, we perform a detailed seismic analysis aiming to identifying earthquake clusters within the seismic crisis and define their spatial and temporal characteristics. Thanks to the dense seismic station coverage in the area, operated by the Hellenic Unified Seismological Network and Corinth Rift Laboratory, we relocate shallow seismicity and compile a high-resolution earthquake catalogue containing ∼1400 earthquakes spanning the first two months of the seismic crisis. We identify 19 earthquake clusters by applying spatio-temporal criteria and define the geometry (strike and dip) using principal component analysis for 11 of them. Our results are consistent with moment tensor solutions computed for the largest earthquake in each cluster. A striking feature of the seismic activity is the west-towards-east migration with a notable increase in Vp/Vs values for each cluster and a slight increase of the dip angle for the identified fault segments. Furthermore, we find that each cluster contains several burst-like, short interevent time, repeating earthquakes, which could be related to aseismic slip or fluid migration. Overall, we show that the 2020–2021 seismic crisis consists of earthquake clusters that bifurcate between swarm-like and main shock–aftershock-like sequences and ruptured both north- and south-dipping high-angle fault segments. The 2020–2021 seismic activity is located between 5 to 8 km, shallower than the low angle north-dipping (∼10°) seismic zone which hosts long-lived repeating sequences at ∼9–10 km depth. This study supports a hypothesis that the low-angle north-dipping seismicity defines the brittle-ductile transition in the western Corinth Gulf, with seismic bursts occurring at shallower depths in the crust.
Omadacycline efficacy in the hollow fibre system model of pulmonary Mycobacterium avium complex and potency at clinically attainable doses
Authors: Chapagain Moti , Pasipanodya Jotam G. , Athale Shruti , Bernal Claude , Trammell Rachel , Howe David , Gumbo Tawanda
Published: February 2022

Objectives

The standard of care (SOC) for the treatment of pulmonary Mycobacterium avium complex (MAC) disease (clarithromycin, rifabutin, and ethambutol) achieves sustained sputum conversion rates of only 54%. Thus, new treatments should be prioritized.

Methods

We identified the omadacycline MIC against one laboratory MAC strain and calculated drug half life in solution, which we compared with measured MAC doubling times. Next, we performed an omadacycline hollow fibre system model of intracellular MAC (HFS-MAC) exposure–effect study, as well as the three-drug SOC, using pharmacokinetics achieved in patient lung lesions. Data was analysed using bacterial kill slopes (γ-slopes) and inhibitory sigmoid Emax bacterial burden versus exposure analyses. Monte Carlo experiments (MCE) were used to identify the optimal omadacycline clinical dose.

Results

Omadacycline concentration declined in solution with a half-life of 27.7 h versus a MAC doubling time of 16.3 h, leading to artefactually high MICs. Exposures mediating 80% of maximal effect changed up to 8-fold depending on sampling day with bacterial burden versus exposure analyses, while γ-slope-based analyses gave a single robust estimate. The highest omadacycline monotherapy γ-slope was −0.114 (95% CI: −0.141 to −0.087) (r2 = 0.98) versus −0.114 (95% CI: −0.133 to −0.094) (r2 = 0.99) with the SOC. MCEs demonstrated that 450 mg of omadacycline given orally on the first 2 days followed by 300 mg daily would achieve the AUC0-24 target of 39.67 mg·h/L.

Conclusions

Omadacycline may be a potential treatment option for pulmonary MAC, possibly as a back-bone treatment for a new MAC regimen and warrants future study in treatment of this disease.
Classic Hoarding Cages Increase Gut Bacterial Abundance and Reduce the Individual Immune Response of Honey Bee (Apis mellifera) Workers
Authors: Gregory Casey L , Fell Richard D , Belden Lisa K , Walke Jenifer B
Published: February 2022

Laboratory experiments have advanced our understanding of honey bee (Apis mellifera) responses to environmental factors, but removal from the hive environment may also impact physiology. To examine whether the laboratory environment alters the honey bee gut bacterial community and immune responses, we compared bacterial community structure (based on amplicon sequence variant relative abundance), total bacterial abundance, and immune enzyme (phenoloxidase and glucose oxidase) activity of cohort honey bee workers kept under laboratory and hive conditions. Workers housed in the laboratory showed differences in the relative abundance of their core gut taxa, an increase in total gut bacterial abundance, and reduced phenoloxidase activity, compared to bees housed in hives.
Quasi-periodic whispers from a transient ULX in M 101: signatures of a fast-spinning neutron star?
Authors: Urquhart Ryan T , Soria Roberto , Di Stefano Rosanne , Cui Kaiming , Esposito Paolo , Israel Gian Luca , Kumar Sammarth , Motta Sara , Pintore Fabio , Riva Giacomo
Published: February 2022

We have studied the unusual time variability of an ultraluminous X-ray source in M 101, 4XMM J140314.2 + 541806 (henceforth, J1403), using Chandra and XMM-Newton data. Over the last two decades, J1403 has shown short-duration outbursts with an X-ray luminosity ∼1–3 × 1039 erg s−1, and longer intervals at luminosities ∼0.5–1 × 1038 erg s−1. The bimodal behaviour and fast outburst evolution (sometimes only a few days) are more consistent with an accretor/propeller scenario for a neutron star than with the canonical outburst cycles of stellar-mass black holes. If this scenario is correct, the luminosities in the accretor and propeller states suggest a fast spin (P ≈ 5 ms) and a low surface magnetic field (B ∼ 1010 G), despite our identification of J1403 as a high-mass X-ray binary. The most striking property of J1403 is the presence of strong ∼600-s quasi-periodic oscillations (QPOs), mostly around frequencies of ≈1.3–1.8 mHz, found at several epochs during the ultraluminous regime. We illustrate the properties of such QPOs, in particular their frequency and amplitude changes between and within observations, with a variety of techniques (Fast Fourier Transforms, Lomb–Scargle periodograms, weighted wavelet Z-transform analysis). The QPO frequency range <10 mHz is an almost unexplored regime in X-ray binaries and ultraluminous X-ray sources. We compare our findings with the (few) examples of very low frequency variability found in other accreting sources, and discuss possible explanations (Lense–Thirring precession of the inner flow or outflow; radiation pressure limit-cycle instability; marginally stable He burning on the neutron star surface).
Discovery of a bright extended X-ray jet in RGB J1512+020A
Authors: Migliori G , Siemiginowska A , Cheung C C , Celotti A , Giroletti M , Giovannini G , Paggi A , Liuzzo E
Published: February 2022

We report the discovery of a bright, extended X-ray jet in the quasar RGB J1512+020A (z = 0.22). Chandra observations show the X-ray core and 13 arcsec  (∼45 kpc projected) extended emission coincident with the radio jet. The jet stands out as one of brightest X-ray jets (LX ∼ 7 × 1043 erg s−1) at low redshift (z < 0.5) discovered so far, with remarkably large X-ray to radio luminosity ratios (LX/Lr up to ∼50). We identified four main components, two unresolved knots and two extended structures, one being the jet brightest feature (JBF). All jet features are also detected in ALMA archival observations. The radio, sub-mm to X-ray spectra of the two knots can be modelled with a single synchrotron component. For the two resolved structures, the ALMA data unveil a turnover of the low-energy continuum at ∼460 GHz. External Comptonization of cosmic microwave background photons can account for the observed X-ray emission if the jet speed remains highly relativistic, with bulk motion Γbulk > 15, up to tens of kiloparsec from the core. However, the comparison with the spectral energy distribution of similar X-ray detected jets shows that the alternative hypothesis of synchrotron emission from an additional population of ultra-high-energy electrons is also possible. We report a tentative (≳2σ) optical detection of the JBF in images of the Dark Energy Camera Legacy Survey. If confirmed, the optical emission should be either the low-energy tail of the radiative component responsible for the X-ray emission or a third, separate component.
iLoci: robust evaluation of genome content and organization for provisional and mature genome assemblies
Authors: Standage Daniel S , Lai Tim , Brendel Volker P
Published: February 2022

We introduce a new framework for genome analyses based on parsing an annotated genome assembly into distinct interval loci (iLoci), available as open-source software as part of the AEGeAn Toolkit (https://github.com/BrendelGroup/AEGeAn). We demonstrate that iLoci provide an alternative coordinate system that is robust to changes in assembly and annotation versions and facilitates granular quality control of genome data. We discuss how statistics computed on iLoci reflect various characteristics of genome content and organization and illustrate how these statistics can be used to establish a baseline for assessment of the completeness and accuracy of the data. We also introduce a well-defined measure of relative genome compactness and compute other iLocus statistics that reveal genome-wide characteristics of gene arrangements in the whole genome context. Given the fast pace of assembly/annotation updates, our AEGeAn Toolkit fills a niche in computational genomics based on deriving persistent and species-specific genome statistics. Gene structure model-centric iLoci provide a precisely defined coordinate system that can be used to store assembly/annotation updates that reflect either stable or changed assessments. Large-scale application of the approach revealed species- and clade-specific genome organization in precisely defined computational terms, promising intriguing forays into the forces of shaping genome structure as more and more genome assemblies are being deposited.
Clinical validation of a spectroscopic liquid biopsy for earlier detection of brain cancer
Authors: Cameron James M , Brennan Paul M , Antoniou Georgios , Butler Holly J , Christie Loren , Conn Justin J A , Curran Tom , Gray Ewan , Hegarty Mark G , Jenkinson Michael D , Orringer Daniel , Palmer David S , Sala Alexandra , Smith Benjamin R , Baker Matthew J
Published: February 2022

Background

Diagnostic delays impact the quality of life and survival of patients with brain tumors. Earlier and expeditious diagnoses in these patients are crucial to reduce the morbidities and mortalities associated with brain tumors. A simple, rapid blood test that can be administered easily in a primary care setting to efficiently identify symptomatic patients who are most likely to have a brain tumor would enable quicker referral to brain imaging for those who need it most.

Methods

Blood serum samples from 603 patients were prospectively collected and analyzed. Patients either had non-specific symptoms that could be indicative of a brain tumor on presentation to the Emergency Department, or a new brain tumor diagnosis and referral to the neurosurgical unit, NHS Lothian, Scotland. Patient blood serum samples were analyzed using the Dxcover® Brain Cancer liquid biopsy. This technology utilizes infrared spectroscopy combined with a diagnostic algorithm to predict the presence of intracranial disease.

Results

Our liquid biopsy approach reported an area under the receiver operating characteristic curve of 0.8. The sensitivity-tuned model achieves a 96% sensitivity with 45% specificity (NPV 99.3%) and identified 100% of glioblastoma multiforme patients. When tuned for a higher specificity, the model yields a sensitivity of 47% with 90% specificity (PPV 28.4%).

Conclusions

This simple, non-invasive blood test facilitates the triage and radiographic diagnosis of brain tumor patients while providing reassurance to healthy patients. Minimizing time to diagnosis would facilitate the identification of brain tumor patients at an earlier stage, enabling more effective, less morbid surgical and adjuvant care.
The Structure of American Political Discontent
Authors: Santucci Jack , Dyck Joshua J
Published: February 2022

We explore the role of “political discontent” as a second dimension of American public opinion. Others have shown that a second dimension tends to capture social and/or racial attitudes. What happens when indicators of discontent are included in such analyses? Using data from two surveys and the ordered optimal classification (OOC) procedure, we scale seven items from the “discontent” literature alongside a larger set of questions that has been shown to capture the two-dimensional structure of mass opinion. Discontent items dominate the second dimension in both data sets. Further, five of the seven items predict voting for “insurgents” in the 2016 presidential primaries. Second-dimension attitudes matter in elections and concern the political system writ large. By extension, the liberal-conservative heuristic gives an incomplete picture of mass political behavior.
Effects of ground-state correlations on the damping of giant dipole resonances in LS closed-shell nuclei
Authors: Tohyama Mitsuru
Published: February 2022

The effects of ground-state correlations on the damping of isovector giant dipole resonances in the LS closed-shell nuclei 16O and 40Ca are studied using extended random phase approximation (RPA) approaches derived from the time-dependent density matrix theory. It is pointed out that unconventional two-body amplitudes of one-particle–three-hole and three-particle–one-hole types that are neglected in most extended RPA theories play an important role in the fragmentation of isovector dipole strength.
Rational design of hydrogels for immunomodulation
Authors: Bu Wenhuan , Wu Yuanhao , Ghaemmaghami Amir M , Sun Hongchen , Mata Alvaro
Published: February 2022

The immune system protects organisms against endogenous and exogenous harm and plays a key role in tissue development, repair and regeneration. Traditional immunomodulatory biologics exhibit limitations including degradation by enzymes, short half-life and lack of targeting ability. Encapsulating or binding these biologics within biomaterials is an effective way to address these problems. Hydrogels are promising immunomodulatory materials because of their prominent biocompatibility, tuneability and versatility. However, to take advantage of these opportunities and optimize material performance, it is important to more specifically elucidate, and leverage on, how hydrogels affect and control the immune response. Here, we summarize how key physical and chemical properties of hydrogels affect the immune response. We first provide an overview of underlying steps of the host immune response upon exposure to biomaterials. Then, we discuss recent advances in immunomodulatory strategies where hydrogels play a key role through (i) physical properties including dimensionality, stiffness, porosity and topography; (ii) chemical properties including wettability, electric property and molecular presentation;and (iii) the delivery of bioactive molecules via chemical or physical cues. Thus, this review aims to build a conceptual and practical toolkit for the design of immune-instructive hydrogels capable of modulating the host immune response.
Fungal-derived selenium nanoparticles and their potential applications in electroless silver coatings for preventing pin-tract infections
Authors: Liang Xinjin , Zhang Shuai , Gadd Geoffrey Michael , McGrath John , Rooney David W , Zhao Qi
Published: February 2022

Pin-tract infections (PTIs) are a common complication of external fixation of fractures and current strategies for preventing PTIs have proven to be ineffective. Recent advances show that the use of anti-infection coatings with local antibacterial activity may solve this problem. Selenium has been considered as a promising anti-infection agent owing to its antibacterial and antibiofilm activities. In this study, selenium nanoparticles (SeNPs) were synthesized via a cost-effective fungi-mediated biorecovery approach and demonstrated excellent stability and homogeneity. To investigate their anti-infection potential, the SeNPs were doped in silver coatings through an electroless plating process and the silver–selenium (Ag–Se) coatings were tested for antibacterial and antibiofilm properties against Staphylococcus aureus F1557 and Escherichia coli WT F1693 as well as corrosion resistance in simulated body fluid. It was found that the Ag–Se coating significantly inhibited S.aureus growth and biofilm formation on the surface, reducing 81.2% and 59.7% of viable bacterial adhesion when compared with Ag and Ag–PTFE-coated surfaces after 3 days. The Ag–Se coating also exhibited improved corrosion resistance compared with the Ag coating, leading to a controlled release of Ag+, which in turn reduced the risk of cytotoxicity against hFOBs. These results suggest that the fungal-derived SeNPs may have potential in use as implant coatings to prevent PTIs.
THE ROLE OF DNA DOUBLE-STRAND BREAK REPAIR THROUGH NON-HOMOLOGOUS END JOINING IN THE DOSE-RATE EFFECT IN TERMS OF CLONOGENIC ABILITY
Authors: Tsuchiya Hisayo , Shimada Mikio , Tsukada Kaima , Meng Qingmei , Kobayashi Junya , Matsumoto Yoshihisa
Published: February 2022

It is generally and widely accepted that the biological effects of a given dose of ionizing radiation, especially those of low linear energy transfer radiations like X-ray and gamma ray, become smaller as the dose rate becomes lower. This phenomenon, known as ‘dose-rate effect (DRE),’ is considered due to the repair of sublethal damage during irradiation but the precise mechanisms for DRE have remained to be clarified. We recently showed that DRE in terms of clonogenic cell survival is diminished or even inversed in rodent cells lacking Ku, which is one of the essential factors in the repair of DNA double-strand breaks (DSBs) through non-homologous end joining (NHEJ). Here we review and discuss the involvement of NHEJ in DRE, which has potential implications in radiological protection and cancer therapeutics.
Cost-Effectiveness of a Multidisciplinary Lifestyle-Enhancing Treatment for Inpatients With Severe Mental Illness: The MULTI Study V
Authors: Deenik Jeroen , van Lieshout Chris , van Driel Harold F , Frederix Geert W J , Hendriksen Ingrid J M , van Harten Peter N , Tenback Diederik E
Published: February 2022

Economic evaluations of lifestyle interventions for people with mental illness are needed to inform policymakers and managers about implementing such interventions and corresponding reforms in routine mental healthcare. We aimed to evaluate changes in healthcare costs 18 months after the implementation of a multidisciplinary lifestyle-enhancing treatment for inpatients with severe mental illness (MULTI) versus treatment as usual (TAU). In a cohort study (n = 114; 65 MULTI, 49 TAU), we retrospectively retrieved cost data in Euros on all patient sessions, ward stay, medication use, and hospital referrals in the quarter year at the start of MULTI (Q1 2014) and after its evaluation (Q3 2015). We used linear regression analyses correcting for baseline values and differences between groups, calculated deterministic incremental cost-effectiveness ratios for previously shown changes in physical activity, metabolic health, psychosocial functioning, and additionally quality of life, and performed probabilistic sensitivity analyses including cost-effectiveness planes. Adjusted regression showed reduced total costs per patient per quarter year in favor of MULTI (B = –736.30, 95%CI: –2145.2 to 672.6). Corresponding probabilistic sensitivity analyses accounting for uncertainty surrounding the parameters showed statistically non-significant cost savings against health improvements for all health-related outcomes in MULTI compared to TAU. It is concluded that MULTI did not increase healthcare costs while improving health outcomes. This indicates that starting lifestyle interventions does not need to be hampered by costs. Potential societal and economic value may justify investment to support implementation and maintenance. Further research is needed to study this hypothesis.
Amlodipine improves the outcomes of regorafenib in metastatic colorectal cancer
Authors: Alandağ Celal , Karaman Elanur , Yüce Elif
Published: February 2022

Regorafenib is a multikinase inhibitor. It is used for metastatic colorectal cancer (mCRC) treatment. It has a mild effect. Regorafenib outcomes, and side effects may vary across patients. This study was aimed to evaluate the factors that affect regorafenib outcomes in mCRC patients. We conducted a single-center and retrospective study. Fifty-six patients were included. All patients had received regorafenib for mCRC. Some clinical and pathological factors and the effects of these factors on overall survival (OS), progression-free survival (PFS), and disease control rates (DCR) were analyzed. Concomitant amlodipine intake with regorafenib improved OS [14.26 vs. 6.97 months; 95% confidence interval, 4.04–20.84; P = 0.031] and DCR at 12th week (90% vs. 46%; P = 0.012). Hepatic metastasis was found as the poorest prognostic factor in both univariate and multivariate analyses. Patients who received chemotherapy after regorafenib had better OS. Good performance status was the strongest indicator of better OS. Patients taking amlodipine for arterial hypertension at the same time with regorafenib had numerically better OS and PFS and statistically better DCR. Amlodipine itself already has anticancer effects, and it has additive anticancer effects with regorafenib. The presence of hepatic metastases was found to be the most important prognostic factor for OS. There were not any predictive factors of side effects to regorafenib.
Sarcopenia and the rate of change of the neutrophil/lymphocyte ratio as predictors of pembrolizumab efficacy in advanced urothelial carcinoma
Authors: Fukata Satoshi , Mizutani Keisuke , Yamamoto Shinkuro , Kuno Takahira , Fukuhara Hideo , Ashida Shingo , Karashima Takashi , Inoue Keiji
Published: February 2022

The objective was to evaluate the usefulness of sarcopenia and the neutrophil/lymphocyte ratio (NLR) as therapeutic efficacy predictors in patients who received pembrolizumab after platinum-based chemotherapy for advanced urothelial carcinoma (aUC). Forty-four patients with aUC were enrolled. Patients’ background characteristics and clinical factors, the skeletal muscle index, and the psoas muscle index were evaluated. The NLR before and during treatment was calculated, and the rate of change of NLR was calculated. The median age was 70 years; the follow-up period was 13.2 months. The response rate was 54%. The nonresponding group had significantly more sarcopenia cases (P = 0.007) and a high rate of change of NLR (P = 0.0076). Progression-free survival (PFS) was significantly shorter in the group with sarcopenia (P = 0.002). Both PFS and overall survival were significantly shorter with an NLR rate of change greater than or equal to 1 (P = 0.001 and P = 0.002). On multivariate analysis, the presence of immune-related adverse events [hazard ratio (HR), 0.3723; 95% confidence interval (CI), 0.14–0.97; P = 0.04] and the NLR rate of change (HR, 3.986; 95% CI, 1.01–15.70; P = 0.048) were independent predictors of PFS. Sarcopenia and the rate of change of NLR appear to be useful as predictors of pembrolizumab efficacy in aUC.
Joint associations between neighborhood walkability, greenness, and particulate air pollution on cardiovascular mortality among adults with a history of stroke or acute myocardial infarction
Authors: Liao Noelle S. , Van Den Eeden Stephen K. , Sidney Stephen , Deosaransingh Kamala , Schwartz Joel , Uong Stephen P. , Alexeeff Stacey E.
Published: February 2022

Background:

Fine particulate matter (PM2.5) is a known risk factor for cardiovascular disease (CVD). Neighborhood walkability and greenness may also be associated with CVD, but there is limited evidence on their joint or interacting effects with PM2.5.

Methods:

Cox proportional hazard models were used to estimate the risk of CVD mortality among adults with a history of acute myocardial infarction and/or stroke living in Northern California. We assessed the independent and joint effects of walkability, greenness (Normalized Differentiated Vegetation Index [NDVI]), and PM2.5 at residential addresses, controlling for age, sex, race/ethnicity, comorbidities, BMI, smoking, revascularization, medications, and socioeconomic status.

Results:

Greenness had a nonlinear association with CVD mortality (P = 0.038), with notably protective effects (HR = 0.87 [95% confidence interval {CI} = 0.78, 0.97]) at higher greenness levels (NDVI ≥ 0.3) and moderate attenuation after adjusting for PM2.5 (HR = 0.92 [95% CI = 0.82, 1.03]) per 0.1 increase in NDVI. Walkability had no independent effect on CVD mortality. PM2.5 had a strong independent effect in models adjusted for greenness and walkability (HR = 1.20 [95% CI = 1.08, 1.33)) per 10 μg/m3 increase in PM2.5. There was an interaction between walkability and PM2.5 (P = 0.037), where PM2.5 had slightly stronger associations in more walkable than less walkable neighborhoods (HR = 1.23 [95% CI = 1.06, 1.42] vs. 1.17 [95% CI = 1.04, 1.32]) per 10 μg/m3 increase in PM2.5. Greenness had no interaction with PM2.5 (P = 0.768) nor walkability (P = 0.385).

Conclusions:

High greenness may be protective of CVD mortality among adults with CVD history. PM2.5 associated CVD mortality risk varies slightly by level of neighborhood walkability, though these small differences may not be clinically meaningful.
How Penn Medicine Is Advancing Care Delivery to Meet More Patients’ Needs
Authors: Mahoney Kevin B. , Wilson-Maher Allison P.
Published: February 2022

The University of Pennsylvania Health System was founded in 1993 as one of the nation’s first integrated academic medical centers. Over the past 29 years, Penn Medicine has systematically built a care delivery system based on three core values: innovation, integration, and impact. The operating strategy is designed to meet the patient’s needs in a traditional brick-and-mortar hospital as well as in an increasingly virtual world. Today’s patient is demanding an omnichannel experience with superior outcomes. Although long discussed in healthcare, such a comprehensive, seamless patient experience is only possible when all four channels of care delivery—hospital, ambulatory, home, and virtual—are sustainably integrated to improve the health of the population through digital innovation and analytics.

The COVID-19 pandemic forced healthcare systems around the world to pour resources into telemedicine and other telehealth tools. This shift is fueling a dramatic shift from a piecemeal digital strategy to a comprehensive approach to the digital world where increased communication among clinicians, caregivers, and patients can lead to improved outcomes at a lower cost.

In this article, we present an illustrative case study focusing on two of four channels of care: the Pavilion at the Hospital of the University of Pennsylvania, where the latest in digital innovation has been built into the walls of our most ambitious capital project to date, and Penn Medicine at Home, which provides home care services, home infusion, and hospice care to patients throughout the region. The new $1.6 billion Pavilion and its technological updates have been seamlessly woven into the longstanding Penn Medicine at Home program. As a system, we did this by learning from both the victories and the setbacks to design for a future of healthcare we could once only imagine.
Associations between duration and volume of muscle-strengthening exercise and clinically assessed hypertension among 10 519 UK adults: a cross-sectional study
Authors: Shakespear-Druery Jane , De Cocker Katrien , Biddle Stuart J.H. , Bennie Jason
Published: February 2022

Background:

Clinical evidence shows that muscle-strengthening exercise (MSE) is important for the treatment and management of hypertension. However, the links between MSE and hypertension in epidemiological research are currently poorly understood. This study examines the association between MSE duration and volume with clinically assessed hypertension.

Methods:

Cross-sectional data (n = 10519, adults ≥ 16 years) were pooled from the Health Survey for England (2012, 2016). Self-reported MSE mode (own bodyweight; gym-based), duration, and volume were tested for associations with sphygmomanometer measured hypertension (SBP ≥ 130 mmHg or DBP ≥ 80 mmHg). Poisson regressions with robust error variance were used to calculate the prevalence ratios of hypertension (outcome variable) across MSE (exposure variables: duration (minutes [0 (reference); 10–20; 21 –59; ≥60/session]); and volume [0 (reference); low <mean; high ≥mean/week]) for each mode and the modes combined.

Results:

Most adults (81.1%) did no MSE. However, in those who did (n = 1984), undertaking any MSE, regardless of mode, duration, or volume, was associated with a reduced likelihood of hypertension (adjusted prevalence ratios 0.61–0.90). When compared with the reference groups (no MSE), some modes had more favourable associations (e.g. ≥60 min/session of own bodyweight MSE; ≥mean min/week of gym-based MSE).

Conclusion:

Irrespective of duration or volume, MSE was associated with a lower prevalence of clinically assessed hypertension. Public-health campaigns and other interventions that successfully promote small-to-moderate increases in MSE participation may reduce the prevalence of hypertension.
Monitoring socioeconomic inequalities across HIV knowledge, attitudes, behaviours and prevention in 18 sub-Saharan African countries
Authors: Hamidouche Mohamed , Ante-Testard Pearl Anne , Baggaley Rachel , Temime Laura , Jean Kevin
Published: February 2022

Objectives:

Socioeconomic inequalities in HIV prevention services coverage constitute important barriers to global prevention targets, especially in sub-Saharan Africa (SSA). We aimed at monitoring these inequalities from population-based survey data in 18 SSA countries between 2010 and 2018.

Methods:

We defined eight HIV indicators aimed at capturing uptake of HIV prevention services among adult participants. Country-specific wealth-related inequalities were measured using the Relative and Slope Index of Inequalities (RII and SII, respectively) and then pooled using random-effects meta-analyses. We compared inequalities between African regions using the Wilcoxon rank-sum test.

Results:

The sample consisted of 358 591 participants (66% women). Despite variability between countries and indicators, the meta-analysis revealed significant levels of relative and absolute inequalities in six out of eight indicators: HIV-related knowledge, positive attitudes toward people with HIV (PWH), condom use at last sexual intercourse, participation to prevention of mother-to-child transmission programs, medical male circumcision and recent HIV testing. The largest inequalities were reported in condom use, with condom use reported five times more among the richest versus the poorest [RII = 5.02, 95% confidence interval (CI) 2.79–9.05] and in positive attitudes toward PWH, with a 32-percentage point difference between the richest and poorest (SII = 0.32, 95% CI 0.26–0.39). Conversely, no significant inequalities were observed in multipartnership and HIV seropositivity among youth. Overall, inequalities tended to be larger in West and Central vs. East and Southern African countries.

Conclusion:

Despite efforts to scale-up HIV-prevention programs, socioeconomic inequalities remain substantial over the continuum of HIV primary and secondary prevention in several SSA countries.
Contraception, fecundity, and pregnancy in women with epilepsy: an update on recent literature
Authors: King Alexa , Gerard Elizabeth E.
Published: February 2022

Purpose of review

Caring for women with epilepsy requires specialized knowledge about potential teratogenicity of antiseizure medications, interactions with hormonal contraception, and pregnancy outcomes.

Recent findings

There has been an improvement in understanding the cognitive outcomes of infants exposed in utero in recent years. Folic acid supplementation helps mitigate the cognitive teratogenicity of antiseizure medications. Recent updates provide reassurance that seizure frequency tends to remain stable throughout pregnancy. There is conflicting evidence about the fecundity impact of epilepsy and antiseizure medications in women with epilepsy.

Recent research highlights the importance of early counseling about the risks and interactions of contraception, pregnancy, and antiseizure medications. More research is needed to understand fertility in women with epilepsy.
Obsessive-compulsive symptoms in major depressive disorder correlate with clinical severity and mixed features
Authors: Olgiati Paolo , Fanelli Giuseppe , Serretti Alessandro
Published: February 2022

Obsessive-compulsive symptoms (OCS) are often reported in patients with bipolar disorder. The aim of this study was to investigate OCS and their related clinical features in major depressive disorder (MDD). The analysis involved 482 outpatients with MDD collected within the Combining Medications to Enhance Depression outcomes trial, who were assessed with scales for depression, suicidality, irritability, hypomanic symptomatology, and other comorbid psychiatric manifestations. OCS were reported in 27% of the sample. Patients with MDD experiencing OCS were found to differ from those not experiencing OCS by a greater severity of depression (d = 0.41, P = 0.0001), more hypomanic symptoms (d = 0.48, P < 0.0001) and mixed features (22% vs. 10%, P = 0.001), increased levels of suicidal thoughts (d = 0.40, P = 0.0001), a lower likelihood of achieving remission after antidepressant treatment (19% vs. 33%, P = 0.0109), as well as more comorbid anxiety disorders (i.e. panic disorder: d = 0.98, P < 0.0001; generalized anxiety disorder: d = 0.74, P < 0.0001; social phobia: d = 0.71, P < 0.0001), and post-traumatic stress disorder (d = 0.81, P < 0.0001). In light of these findings, clinicians should pay more attention to the occurrence of OCS in MDD, as these symptoms may reflect greater clinical severity, poorer treatment outcome, and increased risk for bipolarity.
Demographic profiles of contact lens wearers and their association with lens wear characteristics in Trinidad and Tobago: A retrospective study
Authors: Ngozika Ezinne E , Dipesh Bhattarai , Kingsley Ekemiri K , Gabrielle Harbajan N , Anesha Crooks C , Khathutshelo Mashige P , Ilechie Alex A , Zereid Feriel M , Uchechukwu Osuagwu L
Published: February 2022

Purpose

Contact lenses (CL) remain a popular mode of refractive error correction globally and in the Caribbean, mostly among young people. However, no data on the characteristics of the CL population wearers in the Caribbean is available. This study reported on the characteristics of CL wearers and the associated factors in Trinidad and Tobago (T&T).

Methods

Clinical records of 243 CL wearers attending the University of the West Indies (UWI) optometry clinic between 2017 and 2018 were reviewed. Data on their demographic profiles, CL wearing characteristics including lens type, material, purpose of wear, replacement schedule and care systems were extracted and analyzed. The associations between the demographic characteristics and CL wearing characteristics were also determined.

Results

About half of the respondents wear CL wearers and used them for various purposes such as fashion (more among those aged 18 to 30 years, 61.0%), therapeutic (more among those <18 years, 43.8%, P = 0.001) and refractive error correction purposes (more in those >40 years, P =0.001). Females were more likely to use CLs for fashion compared with males (67.0% versus 40.7%). Age (P<0.0005) and gender (P=0.030) were associated with the lens materials. Those aged 18-30 years were more likely use hydrogels compared with the younger ones (64.1% versus 25.0%). Rigid gas permeable (RGP) CL use was more common in males than females (21.8% versus 10.9%, P = 0.031). Daily disposables were predominantly used by younger respondents (18-30 year-olds, 31.3%, P < 0.001) and more in females than males (66.7% vs 49.4%, P = 0.040).

Conclusions

Contact lens use appears be more common among younger females for fashion and older males for refractive correction. Age, gender and employment status were the main determinants of lens wear among respondents attending the university clinic in T&T.
Can imputation in a European country be improved by local reference panels? The example of France
Authors: Herzig Anthony F. , Velo-Suárez Lourdes ,   Frex Consortium,   FranceGenRef Consortium, Dina Christian , Redon Richard , Deleuze Jean-François , Génin Emmanuelle
Published: February 2022

France has a population with extensive internal fine-structure; and while public imputation reference panels contain an abundance of European genomes, there include few French genomes. Intuitively, using a ‘study specific panel’ (SSP) for France would therefore likely be beneficial. To investigate, we imputed 550 French individuals using either the University of Michigan imputation server with the Haplotype Reference Consortium panel, or in-house using an SSP of 850 whole-genome sequenced French individuals.

With approximate geo-localization of both our target and SSP individuals we are able to pinpoint different scenarios where SSP-based imputation would be preferred over server-based imputation or vice-versa. We could also show to a high degree of resolution how the proximity of the reference panel to a target individual determined the accuracy of both haplotype phasing and genotype imputation.

Previous comparisons of different strategies have shown the benefits of combining public reference panels with SSPs. Getting the best out of both resources simultaneously is unfortunately impractical. We put forward a pragmatic solution where server-based and SSP-based imputation outcomes can be combined based on comparing posterior genotype probabilities. Such an approach can give a level of imputation accuracy markedly in excess of what could be achieved with either strategy alone.
Higher knee hypertension in patients with hemiplegia correlates lower lateral and medial meniscus volume in the paretic leg
Authors: Li Wenshan , Li Tiancong , Xi Xiaoshuang , Zhang Rong , Sun Weishuang , Han Conglin , Zhang Dan , Gong Weijun
Published: February 2022

Stroke is a disease with high morbidity and disability rate. After stroke, slower walking velocity, shorter step length, higher cadence, larger step width, and longer stance phase duration can be apparently observed. Additionally, these abnormal gait parameters eventually lead to knee hyperextension, known as genu recurvatum. Walking with such knee hyperextension usually induces knee pain and joint lesions, leading to cumulative damage and degenerative changes and further decreasing the standing phase’s stability. However, do higher angles of knee hyperextension have any correlation between the gait parameters, the kinematics, the kinetic parameters, the meniscus volume, and the water content of meniscus in paretic and non-paretic legs? This study attempted to answer these questions. The results revealed that 1) longer time since hemiplegia led to larger angles of knee hyperextension, 2) larger angles of knee hyperextension led to more tears in medial/lateral meniscus, and 3) larger angles of knee hyperextension decreased water content of the lateral meniscus in the non-paretic leg but increased water content of the medial meniscus. This was the first study to demonstrate these three above-mentioned observations through magnetic resonance imaging and motion capture system. These results suggested that 1) the knee hyperextension needed to be diagnosed and treated as early as possible; 2) the time since hemiplegia could be an indicator of sign of knee hyperextension; and 3) it might be not effective to identify the knee hyperextension by using spatial-temporal gait parameters.