bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between PD‐L1 expression and initial brain metastasis in patients with non‐small cell lung cancer and its clinical implications
Authors: Lee Kyoungmin , Choi Yoon J. , Kim Jung S. , Kim Dae S. , Lee Sung Y. , Shin Bong K. , Kang Eun J.
Published: June 2021

Background

Brain metastases frequently occur in patients with non‐small cell lung cancer (NSCLC) resulting in a poor prognosis. Here, we investigated the association between PD‐L1 expression and brain metastasis in patients with NSCLC and its clinical significance.

Methods

A total of 270 patients diagnosed with metastatic NSCLC who underwent PD‐L1 testing on their tumor tissue between January 2017 and March 2019 were retrospectively reviewed. The VENTANA PD‐L1 (SP263) assay was used, and positive PD‐L1 expression was defined as staining in ≥1% of tumor cells.

Results

Positive PD‐L1 expression was observed in 181 (67.0%) patients, and 74 (27.4%) patients had brain metastasis at diagnosis. Synchronous brain metastases were more frequently observed in PD‐L1‐positive compared with PD‐L1‐negative patients (31.5% vs. 19.1%, p = 0.045). Multiple logistic regression analysis identified positive PD‐L1 expression (odds ratio [OR]: 2.24, p = 0.012) as an independent factor associated with synchronous brain metastasis, along with the histological subtype of nonsquamous cell carcinoma (OR: 2.84, p = 0.003). However, the incidence of central nervous system (CNS) progression was not associated with PD‐L1 positivity, with a two‐year cumulative CNS progression rate of 26.3% and 28.4% in PD‐L1‐positive and PD‐L1‐negative patients, respectively (log rank p = 0.944). Furthermore, positive PD‐L1 expression did not affect CNS progression or overall survival in patients with synchronous brain metastasis (long rank p = 0.513 and 0.592, respectively).

Conclusions

Initial brain metastases are common in NSCLC patients with positive PD‐L1 expression. Further studies are necessary to understand the relationship between early brain metastasis and cancer immunity.
Attitudes toward the Use of Force: Instrumental Imperatives, Moral Principles, and International Law
Authors: Dill Janina , Schubiger Livia I.
Published: June 2021

What informs ordinary citizens' attitudes toward the use of force? Previous research identifies several key concerns in public opinion toward war, but does not directly evaluate the relative importance of these considerations. We articulate three distinct logics of war support—moral, legal, and instrumental—and use an experimental survey with 3,000 U.S. respondents to test how ordinary citizens make trade‐offs among multiple competing imperatives relevant for decision making in war. Our design is the first to isolate to what extent substantive legal demands, instrumental military imperatives, and specific moral principles are reflected in respondents' preferences. Although all logics have some resonance, we find that respondents' preferences are remarkably consistent with several core demands of international law even though respondents are not told that the legality of the use of force is at stake. Only the imperative to minimize U.S. military casualties overwhelms both legal and moral demands.
Elective abdominal wall hernia repair surgical mortality—A systematic review of the literature and peer review of mortality in Australia
Authors: Patiniott Paul , Reid Jessica , Maloney Ryan T. , Karatassas Alex , Maddern Guy
Published: June 2021

Background

This study systematically reviewed the literature regarding perioperative mortality in human adults undergoing elective surgical abdominal wall hernia repair, including an audit of the Royal Australasian College of Surgeons (RACS) Australian and New Zealand Audit of Surgical Mortality (ANZASM) database.

Methods

A systematic review was conducted in accordance with PRISMA guidelines for the reporting of systematic reviews and meta‐analysis of observational studies. Cochrane Library, PubMed, MEDLINE and Embase database searches and data extraction were conducted from June 1979 to October 2019. Statistical analysis was undertaken utilising denominator values for elective hernia procedures derived from the Australian Institute of Health and Welfare (AIHW) data. Risk‐adjusted perioperative mortality rates for the relevant procedures were also produced, using a binary logistic regression for the risk adjustment.

Results

Through systematic review of the literature, it was established that the overall reported perioperative mortality in human adults undergoing elective surgical abdominal wall hernia repair was low (0.1%–0.5%). Using ANZASM and AIHW data, the calculated risk‐adjusted mortality rate for Australian patients was found to be significantly lower (0.04%–0.06%, p < 0.001).

Conclusion

The risk‐adjusted mortality rate for elective abdominal wall hernia surgery in Australia is very low and compares favourably to international cohorts. Despite low absolute numbers, the factors which were most significantly associated with increased perioperative mortality in patients undergoing elective surgical abdominal wall hernia repair were increased age, cardiorespiratory co‐morbidity and incisional hernia repair.
Comparison of oesophageal and gastric cancer in the evaluation of urgent endoscopy referral criteria
Authors: Kumar Liana , Kholmurodova Feruza , Bull Jeff , Bright Tim , Watson David I. , Shenfine Jonathan
Published: June 2021

Background

The objective of the study is to identify differences in epidemiology and clinical presentation between oesophageal and gastric cancer and to evaluate the sensitivity of the Australian urgent endoscopy referral guidelines.

Methods

Design; Observational cohort study from February 2013 to October 2018. Setting: A single tertiary specialist oesophago‐gastric cancer centre: Flinders Medical Centre, South Australia. Participants: Patients with oesophageal and gastric cancer that had surgery with curative intent 61.9% oesophageal cancer, 38.1% gastric cancer. Main outcome measures: Differences between oesophageal and gastric cancer in terms of demographical variables, first presenting symptoms and sensitivity of the Australian urgent endoscopy referral guidelines.

Results

Oesophageal cancer presented at a median age of 64.4 years old, with a male: female ratio of 6:1, and dysphagia as the first presenting symptom in 61%. Gastric cancer presented at a median age of 69.5, with a 2:1 male: female ratio and predominantly non‐specific symptoms—blood loss (36%), weight loss, nausea, and anorexia (21%) and epigastric pain (13%). The Australia urgent endoscopy referral guidelines had 76% sensitivity for oesophageal cancer detection compared with a 33% sensitivity for gastric cancer in this cohort. Delays from symptom onset to referral occurred for most patients with timeframes over four times the recommended 2‐week timeframe.

Conclusion

There should be a separate urgent referral guideline for oesophageal and gastric cancer. These should include dysphagia for oesophageal cancer and blood loss (anaemia, haematemesis, melaena) for gastric cancer. Delays from symptom onset to referral indicate the need for further education of the public and general practitioners on symptoms warranting urgent referral.
A prospective case series of Fournier's gangrene at a tertiary centre involving adjacent organs
Authors: David Rowan , Traeger Luke , Kahokehr Arman , Miller John , Ashrafi Akbar
Published: June 2021

Background

Recent studies of patients with Fournier's gangrene (FG) highlight the importance of early surgical intervention in improving mortality rates. We prospectively determined subgroups of patients with FG at high risk of severe local morbidity.

Methods

We prospectively evaluated all patients diagnosed with FG at a tertiary hospital (1 January 2018 to 1 January 2021). Data were collated on demographics, comorbidity, infection source, treatment and clinical outcomes.

Results

We identified 14 consecutive male patients with a median (interquartile range) age of 57 (50–64) years. Most common risk factors were diabetes (n = 10, 71%) and obesity (n = 10, 71%). Median (range) HbA1c was 11.20 (7.5–15.3), and body mass index of 41.25 (23.7–70.0). Seven patients had adjacent organ involvement (AOI), involving the corporal bodies (57%) and testes (43%). The most common suspected source was dermatological (50%), followed by genitourinary (29%) and gastrointestinal (GI) (21%). Median (interquartile range) hospital length of stay (LOS) was 32 (8.5–30.75) days. Patients with AOI were more likely to have a suspected GI source, need mechanical ventilation (p = 0.023), a significantly longer LOS (p = 0.015) and time to wound closure (p = 0.04). Patients with suspected dermatological origin of infection, had a significantly lower rate of AOI (p = 0.029), mechanical ventilation (p = 0.029) and a shorter LOS (p = 0.035).

Conclusion

In our prospective series, FG is associated with a high rate of AOI and suspected non‐dermatological origin of infection, which confers significant perioperative morbidity including the need for mechanical ventilation, LOS and longer time from initial debridement to wound closure.
A decade review of emergency obturator hernia repairs
Authors: Diab Jason , Badiani Sarit , Berney Christophe R.
Published: June 2021

Background

Obturator hernia is a rare pelvic hernia associated with a high morbidity and mortality. It most commonly occurs in elderly, multiparous females with symptoms and signs of small bowel obstruction. We present an Australian hospital network experience on emergency presentations of obturator hernias highlighting differences between clinical profile and surgical management.

Methods

A retrospective review of adult patients diagnosed with acute obturator hernia during a 10 year period (2010–2020) was conducted across 10 major Sydney hospitals in New South Wales, Australia.

Results

Obturator hernia was diagnosed in 18 patients (mean 82.7 years, range: 60–96 years old), all confirmed on pre‐operative computed tomography imaging. The most common presentations were elderly women demonstrating clinical features of a small bowel obstruction. The mean onset of symptoms from home to hospital admission was 49.4 h. Non‐survivors had a significantly elevated urea level (15.6 vs. 7.8 mmol/L, p = 0.036) at presentation and a longer delay from onset of presenting symptoms to diagnosis (84.0 vs. 36.2 h, p = 0.028). Eleven patients underwent urgent laparotomy and six laparoscopic repairs. The mean operative time was 101.0 min. The average hospital length of stay was 16.2 days with a mortality rate of 27.8%.

Conclusion

Timely diagnosis and operative intervention for obturator hernia is the cornerstone of management.
Herpes simplex virus PCR in 2230 explanted corneal buttons
Authors: Tóth Gábor , Berkó‐Göttel Barbara , Seitz Berthold , Langenbucher Achim , Stachon Tanja , Pluzsik Milán Tamás , Nagy Zoltán Zsolt , Smola Sigrun , Szentmáry Nóra
Published: June 2021

Purpose

To determine herpes simplex virus (HSV) DNA prevalence and mean cycle threshold of polymerase chain reaction (PCR) in corneal tissue of patients with penetrating keratoplasty (PKP), with (HSK+) and without (HSK−) previous clinical herpetic keratitis history.

Methods

Retrospective review of recipient corneal buttons which were explanted through PKP between March 2010 and September 2018 at the Department of Ophthalmology, Saarland University Medical Center in Homburg/Saar, Germany. Corneal tissue samples were analysed by real‐time PCR for the presence of HSV DNA. For each subject, clinical data, including patients’ demographics and clinical diagnoses, were collected.

Results

In total, 2230 corneal samples (age at the time of the surgery 57.3 ± 19.2 years) of 1860 patients were analysed. HSV PCR was positive in 137 (6.1%) corneal samples, with a 30.57 ± 6.01 (range 14–39) mean cycle threshold (Ct) value. Two hundred ninety‐eight (13.4%) corneas of 266 patients were clinically HSK+, and 1932 (86.6%) corneas of 1600 patients were clinically HSK−. HSV DNA was detected significantly more frequently (p < 0.0001) in HSK+ corneal samples (108 corneal samples; 36.2%), than in HSK− corneal samples (29 corneal samples; 1.5%). Ct value was significantly lower in HSK+ than in HSK‐ corneal samples (29.8 ± 5.8 versus 32.6 ± 5.9; p = 0.008).

Conclusion

Our data demonstrate that a positive clinical history of HSK is related to HSV PCR positivity in about every 2.8th patient. In addition, about every 66th explanted corneal tissue is HSV PCR‐positive despite the lack of clinical suspicion. These patients may need additional local/systemic antiviral treatment to avoid newly acquired HSK following penetrating keratoplasty.
Repeatability and inter‐observer variation of choroidal thickness measurements using swept‐source optical coherence tomography in myopic danish children aged 6–14 years
Authors: Asmussen Anders , Smith Bjarke S. , Møller Flemming , Jakobsen Trine M.
Published: June 2021

Purpose

To estimate repeatability and inter‐observer variation of choroidal thickness measurements in myopic Danish children aged 7–14 years using swept‐source optical coherence tomography (SS‐OCT).

Methods

Thirty‐nine children were enrolled. Optical correction was single‐vision spectacles (SVS) or orthokeratology lenses (OKL). Three repeated 7 × 7 mm 3‐dimensional SS‐OCT macula scans and three repeated 9 mm SS‐OCT line scans were collected for each child using a DRI OCT Triton. Choroidal thickness was measured using three different methods: line scan method 1 (LM1), line scan method 2 (LM2) and 3D macula scan method (3DM). Segmentation was adjusted if needed. Coefficients of repeatability (CR) and limits of agreement (LoA) were calculated.

Results

The CRs ranged from 13.4 to 23.9 µm, 14.5 to 26.2 µm and 5.2 to 10.7 µm for LM1, LM2 and 3DM, respectively. The LoA ranged from −22.9 to +31.5 µm, −23.3 to +32.2 µm and −10.2 to +12.4 µm for LM1, LM2 and 3DM, respectively. Segmentation was adjusted in most scans (63%–92%). Mean choroidal thickness ranged from 142.2 ± 47.2 to 253.8 ± 60.9 µm and 190.1 ± 64.0 to 299.0 ± 55.8 µm for the SVS and OKL groups, respectively, measured by 3DM.

Conclusion

The 3DM was the most repeatable method in this paediatric population. It yielded a CR of 10.7 µm, confidence interval 2.4 µm, which makes the minimal detectable difference between two measurements 13.1 µm. Most inter‐observer variation could be explained by the intramethod variation. Segmentation adjustment on 3D macula scans did not increase CR on a group level.
The role of goal adjustment during rehabilitation from stroke
Authors: Cho Yongwon , Hamm Jeremy M. , Heckhausen Jutta , Cramer Steven C.
Published: June 2021

We investigated motivational regulation involving adjustment of recovery goals in post‐stroke rehabilitation via standard in‐clinic physiotherapy and in‐home telerehabilitation (TR). We used a secondary dataset collected at 11 US sites as part of a clinical trial using video games and game control pads designed to induce certain arm movements required for recovery (n = 124; Mage = 61.44, SD = 13.30). Participants were randomly assigned to either the TR or in‐clinic condition and underwent 36 therapy sessions, reporting on their activity‐inherent enjoyment for 6–8 weeks. Compared with the in‐clinic patients and TR patients with high game performance, TR patients with lower game performance reported lower activity‐inherent enjoyment, which is an important motivational resource for successful recovery. The results suggest that these differences occur because TR patients become discouraged by low game score feedback, which may have signaled a poor prospect for recovery. However, the results also suggest that low game performers who successfully adjusted their recovery goals were resilient to the impact of low game score feedback on their motivational resources and satisfaction with therapy. The findings suggest that goal adjustment may be particularly beneficial when patients are discouraged by feedback indicating suboptimal recovery prospects.
Personality and environmental outcomes: The role of moral anger in channeling climate change action and pro‐environmental behavior
Authors: Panno Angelo , De Cristofaro Valeria , Oliveti Camilla , Carrus Giuseppe , Donati Maria Anna
Published: June 2021

The overarching aim of the present research is to investigate whether and how HEXACO personality traits relate to climate change action, pro‐environmental behavior, and moral anger. A sample of 268 community participants provided responses for measures of the HEXACO model, moral anger, intention to engage in climate change action, and pro‐environmental behavior. Hierarchical tests indicated that (1) Openness to Experience outperformed the other HEXACO personality traits in predicting climate change action, whereas (2) both Openness to Experience and Honesty–Humility outperformed the other HEXACO personality traits in predicting pro‐environmental behavior, controlling for participants’ gender, age, education, and employment status. Specifically, mediation analyses showed that (3) Openness to Experience was related to climate change action both directly and indirectly via moral anger. Furthermore, (4) Openness to Experience and Honesty–Humility were independently related to pro‐environmental behavior both directly and indirectly via moral anger.
Targeting vulnerable populations: The ethical implications of data mining, automated prediction, and focused marketing
Authors: Callanan Gerard A. , Perri David F. , Tomkowicz Sandra M.
Published: June 2021

This article presents an overview of the ethically questionable business strategies of data mining and automated prediction with respect to vulnerable populations of consumers. It first provides a summary of the privacy and ethical issues that arise when high‐tech internet‐based organizations collect and analyze large quantities of personal data from the users of their systems and how these data are analyzed to make assumptions and projections on individual behaviors. It then discusses how these actions might be technically legal but violate established moral and ethical standards. The paper also highlights the role that governments can play in limiting the ability of large tech‐based companies to mine personal information for commercial application. The article closes with suggestions for future research.
Manifestations of corporate social responsibility as sensemaking and sensegiving in a hydrocarbon industry
Authors: Andrews Nathan
Published: June 2021

There is a large body of literature that examines different dimensions of corporate social responsibility (CSR) in Africa, with many focusing on the false promises of these corporate initiatives. Contrary to simplistic claims of CSR being merely window‐dressing, however, this paper reveals that although several rhetorical proclamations underpin the idea, such statements are often given instrumental meaning through diverse mechanisms (e.g., interpretation of cues toward the proactive (re)construction of identity, (inter)subjective discourses on social legitimacy, and acts of “issue selling”) that help to enact particular characteristics of the corporation. The paper specifically employs the organizational concepts of sensemaking and sensegiving to explain how, through CSR activities, hydrocarbon companies in Ghana construct and (re)affirm a particular reality for its stakeholders. The findings suggest that by having significant leverage over the (re)construction of its identity and claims around social legitimacy and performance, the corporation gives sense to and further sustains its authority over societal norms and expectations around what social responsibility entails. The evidence presented contributes to scholarship that considers the corporation as a complex nexus of multiple relations, contested narratives, and practices.
Improving Access to Psychological Therapies (IAPT) has potential but is not sufficient: How can it better meet the range of primary care mental health needs?
Authors: Martin Carla , Iqbal Zaffer , Airey Nicola D. , Marks Lucy
Published: June 2021

Background

The Improving Access to Psychological Therapies (IAPT) programme has been impactful in increasing access to psychological therapies at primary care level. However, it remains unclear whether IAPT’s widely disseminated achievements include the reduction in service users’ transition to secondary care services and whether IAPT services are providing interventions that match the level of complexity of presenting problems of those who are referred.

Aims

This review sets out to clarify the clinical characteristics of IAPT cohorts, whether the interventions provided target these characteristics, and whether outcomes are related to the use of the stepped‐care model advocated in the operationalization of IAPT services.

Method

A systematic literature search was undertaken on PsycINFO, MEDLINE, and Embase using the terms: IAPT, anxiety, and depression.

Results

Of 472 paper identified, 24 articles were deemed pertinent. It appears that IAPT cohorts are complex and current service delivery frameworks may not meet their needs. IAPT developments and research for long‐term physical health conditions and serious mental illness have been recently advocated, though whether these are sufficient and viable when set in IAPT’s prescriptive backdrop remains unclear.

Conclusions

Improving Access to Psychological Therapies provision and research at present does not adequately consider the complexity of its clientele in the context of treatment outcomes and service delivery. Recommendations are provided for future research and practice to tackle these deficiencies.

Practitioner Points

Improving Access to Psychological Therapies (IAPT) has significantly increased access to psychological therapies within primary care over the last decade, though it is unclear whether its interventions are sufficiently tailored to meet the actual levels of complexity of its clientele and prevent them from needing onward referral to secondary care as originally envisaged.

Given the ongoing focus on and investment in IAPT informed developments into long‐term conditions and serious mental illness, this review considers whether additional elucidation of the model’s original objectives is required, as a precursor to its expansion into other clinical areas.

The review indicates that there is a stark lack of data pertaining to the generalisable, real‐world clinical benefits of the IAPT programme as it currently stands.

Recommendations are provided for future areas of research, and practice enhancements to ensure the value of IAPT services to clients in the wider context of NHS mental health services, including the interface with secondary care, are considered.
Distinct maternal and fetal pregnancy outcomes in women with sickle cell disease can be predicted using routine clinical and laboratory data
Authors: Malinowski A. Kinga , Kuo Kevin H. M. , Tomlinson George A. , Palcu Patricia , Ward Richard , Shehata Nadine
Published: June 2021

We aimed to identify risk factors for adverse outcomes in pregnancies of women with sickle cell disease (SCD) and develop risk prediction models. Models were derived from a retrospective cohort of pregnant women with SCD and constructed using generalised estimating equation logistic regression, with clustering by woman. Maternal event(s) consisted of acute anaemia; cardiac, pulmonary, hepatobiliary, musculoskeletal, skin, splenic, neurological or renal complications, multi‐organ failure, venous thromboembolism, admission‐requiring vaso‐occlusive events (VOE), red cell transfusion, mortality or hypertensive disorder of pregnancy. Fetal events included preterm birth, small‐for‐gestational‐age or perinatal mortality. Of 199 pregnancies, 71% and 45% resulted in adverse maternal and fetal outcomes respectively. Low first‐trimester haemoglobin, admission‐requiring VOE in the year before pregnancy, multiple transfusions before pregnancy, SCD genotype and previous cardiac complications predicted maternal risk. Younger age and SCD genotype allowed early prediction of fetal risk (model‐F1). Adding maternal event(s) and high lactate dehydrogenase enabled re‐assessment of fetal risk with advancing gestation (model‐F2). Models were well calibrated and moderately discriminative for maternal outcome (c‐statistic 0·81, cross‐validated value 0·79) and fetal outcome (model‐F1 c‐statistic 0·68, cross‐validated value 0·65; model‐F2 c‐statistic 0·72, cross‐validated value 0·68). The models will allow early identification of women with SCD at high risk of adverse events, permitting early targeted interventions and ongoing fetal risk re‐assessment enabling intensification of surveillance and optimisation of delivery timing.
Non‐invasive quantification of pressure‐volume loops from cardiovascular magnetic resonance at rest and during dobutamine stress
Authors: Sjöberg Pia , Seemann Felicia , Arheden Håkan , Heiberg Einar
Published: June 2021

Non‐invasive quantification of pressure‐volume (PV) loops from brachial pressure and cardiovascular magnetic resonance is a validated method but its application has been limited to resting heart rates. The aim of this study was to improve the previous method and validate it against invasive left‐ventricular pressure measurements in an experimental porcine model, and further apply it to 16 healthy humans at rest and during dobutamine stress. In addition, the improved method calculates the arterial elastance which provides the computation of the ratio of effective arterial (Ea) to maximal ventricular elastance (Emax) representing the ventricular‐arterial coupling. In the porcine model, the differences between the improved non‐invasively derived PV loops and invasively measured PV loops were for stroke work (mean ± SD) 0.00 ± 0.03 J, ventricular efficiency −1.1 ± 0.4%, and contractility 1.1 ± 0.1 mmHg/ml. In human subjects during dobutamine stress, stroke work increased from 1.3 ± 0.3 to 1.7 ± 0.4 J, ventricular efficiency from 71 ± 4 to 82 ± 4%, contractility from 1.3 ± 0.2 to 2.3 ± 0.6 mmHg/ml, and the ratio of arterial to ventricular elastance decreased from 0.96 to 0.56. The improved method for non‐invasive PV loops constitutes a more robust diagnostic tool for cardiac disease states in a wider range of study cohorts at both rest and during stress.
Pharmacokinetics, bioavailability, and bioequivalence of lower‐sodium oxybate in healthy participants in two open‐label, randomized, crossover studies
Authors: Chen Cuiping , Jenkins Jack , Zomorodi Katie , Skowronski Roman
Published: June 2021

American Academy of Sleep Medicine practice parameters designate sodium oxybate (SXB) as a standard of care for cataplexy, excessive daytime sleepiness (EDS), and disrupted night‐time sleep in narcolepsy. Recently, a lower‐sodium oxybate (LXB) with 92% less sodium than SXB was approved in the United States for the treatment of cataplexy or EDS in patients 7 years of age and older with narcolepsy. Two phase I, open‐label, randomized, single‐dose crossover pharmacokinetic studies in healthy adults were conducted. Single 4.5‐g oral doses of LXB and SXB were administered in a fasted or fed state. In the fasted state at equivalent oxybate doses, LXB, compared with SXB, had a lower maximum plasma concentration (Cmax; study 1 [total aqueous volume, 240 ml]: 101.8 vs. 135.7 µg/ml; study 2 [60 ml]: 94.6 vs. 123.0 μg/ml), delayed time to Cmax (Tmax; study 1: 0.75 vs. 0.5 h; study 2: 1.0 vs. 0.5 h), but similar area under the curve (AUC; study 1: AUC0‐t, 235.4 vs. 263.9 μg∙h/ml; AUC0‐∞, 236.5 vs. 265.2 μg∙h/ml; study 2: AUC0‐t, 241.5 vs. 254.7 μg∙h/ml; AUC0‐∞, 243.1 vs. 256.3 μg∙h/ml). Bioequivalence criteria were met for AUC but not Cmax (both studies). Cmax and AUC were lower under fed than fasted conditions (LXB and SXB); differences between fed versus fasted were smaller for LXB than SXB. These pharmacokinetic differences between LXB and SXB are likely due to the lower sodium content in LXB. Pooled analyses demonstrated that a higher Cmax is associated with a higher incidence of nausea and vomiting.
Immune‐viral dynamics modeling for SARS‐CoV‐2 drug development
Authors: Cao Youfang , Gao Wei , Caro Luzelena , Stone Julie A.
Published: June 2021

Coronavirus disease 2019 (COVID‐19) global pandemic is caused by severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) viral infection, which can lead to pneumonia, lung injury, and death in susceptible populations. Understanding viral dynamics of SARS‐CoV‐2 is critical for development of effective treatments. An Immune‐Viral Dynamics Model (IVDM) is developed to describe SARS‐CoV‐2 viral dynamics and COVID‐19 disease progression. A dataset of 60 individual patients with COVID‐19 with clinical viral load (VL) and reported disease severity were assembled from literature. Viral infection and replication mechanisms of SARS‐CoV‐2, viral‐induced cell death, and time‐dependent immune response are incorporated in the model to describe the dynamics of viruses and immune response. Disease severity are tested as a covariate to model parameters. The IVDM was fitted to the data and parameters were estimated using the nonlinear mixed‐effect model. The model can adequately describe individual viral dynamics profiles, with disease severity identified as a covariate on infected cell death rate. The modeling suggested that it takes about 32.6 days to reach 50% of maximum cell‐based immunity. Simulations based on virtual populations suggested a typical mild case reaches VL limit of detection (LOD) by 13 days with no treatment, a moderate case by 17 days, and a severe case by 41 days. Simulations were used to explore hypothetical treatments with different initiation time, disease severity, and drug effects to demonstrate the usefulness of such modeling in informing decisions. Overall, the IVDM modeling and simulation platform enables simulations for viral dynamics and treatment efficacy and can be used to aid in clinical pharmacokinetic/pharmacodynamic (PK/PD) and dose‐efficacy response analysis for COVID‐19 drug development.
Diagnostic added value of interictal magnetic source imaging in presurgical evaluation of persons with epilepsy: A prospective blinded study
Authors: Tripathi Manjari , Kaur Kirandeep , Ramanujam Bhargavi , Viswanathan Vibhin , Bharti Kamal , Singh Gaurav , Singh Vivek , Garg Ajay , Bal Chandra Sekhar , Tripathi Madhavi , Sharma Mehar Chand , Pandey Ravindra , Dash Deepa , Mandal Pravat , Chandra Poodipedi Sarat
Published: June 2021

Background and purpose

In presurgical evaluation for epilepsy surgery, information is sourced from various imaging modalities to accurately localize the epileptogenic zone. Magnetoencephalography (MEG) is a newer noninvasive technique for localization. However, there is limited literature to evaluate if MEG provides additional advantage over the conventional imaging modalities in clinical decision making. The objective of this study was to assess the diagnostic added value of MEG in decision making before epilepsy surgery.

Method

This was a prospective observational study. Patients underwent 3 h of recording in a MEG scanner, and the resulting localizations were compared with other complimentary investigations. Added value of MEG (considered separately from high‐density electroencephalography) was defined as the frequency of cases in which (i) the information provided by magnetic source imaging (MSI) avoided implantation of intracranial electrodes and the patient was directly cleared for surgery, and (ii) MSI indicated additional substrates for implantation of intracranial electrodes. Postoperative seizure freedom was used as the diagnostic reference by which to measure the localizing accuracy of MSI.

Results

A total of 102 patients underwent epilepsy surgery. MEG provided nonredundant information, which contributed to deciding the course of surgery in 33% of the patients, and prevented intracranial recordings in 19%. A total of 76% of the patients underwent surgical resection in sublobes concordant with MSI localization, and the diagnostic odds ratio for good (Engel I) outcome in these patients was 2.3 (95% confidence interval 0.68, 7.86; p = 0.183) after long‐term follow‐up of 36 months.

Conclusion

Magnetic source imaging yields additional useful information which can significantly alter as well as improve the surgical strategy for persons with epilepsy.
Tuning structural parameters of neural networks using genetic algorithm: A credit scoring application
Authors: Kazemi Hamid Reza , Khalili‐Damghani Kaveh , Sadi‐Nezhad Soheil
Published: June 2021

Neural networks (NNs) have successfully been applied to classification problems including credit scoring. The tuning of the structural parameters of the NNs has a direct impact on their accuracy. In this paper, a hybrid approach based on the genetic algorithm (GA) is proposed to adjust the structural parameters of a classifier NN to achieve high accuracy. Two well‐known credit scoring datasets—Australian and German datasets—are used to test the proposed approach. The results indicate that the proposed hybrid approach is able to successfully tune the structural parameters, while the accuracy of classification is enhanced and its complexity dramatically diminished in comparison with other existing approaches. The performance of the proposed algorithm has been investigated through statistical analysis The best‐known solutions achieved by the proposed approach have an accuracy equal to 97.78% and 87.1% for Australian and German datasets, respectively. The results indicate 2.68% and 0.1% improvement in comparison with the best results reported in the literature, respectively. This improvement is important for real cases in which millions of loans are allocated using credit scoring approaches.
Anomaly detection in autonomous electric vehicles using AI techniques: A comprehensive survey
Authors: Dixit Palak , Bhattacharya Pronaya , Tanwar Sudeep , Gupta Rajesh
Published: June 2021

The next wave in smart transportation is directed towards the design of renewable energy sources that can fuel automobile sector to shift towards the autonomous electric vehicles (AEVs). AEVs are sensor‐driven and driverless that uses artificial intelligence (AI)‐based interactions in Internet‐of‐vehicles (IoV) ecosystems. AEVs can reduce carbon footprints and trade energy with peer AEVs, smart grids (SG), and roadside units (RSUs). It supports green transportation vision. However, the sensor information, energy units, and user data are exchanged through open channels, and thus, are susceptible to various security and privacy attacks. Thus, AEVs can be remotely operated and directed by malicious entities that can propagate false updates to the peer nodes in IoV environment. This can cause the failure of components, congestion, as well as the entire disruption of IoV network. Globally researchers and security analysts have addressed solutions that pertain to specific security requirements, but still, the detection and classification of malicious AEVs is a widely studied topic. Malicious AEVs exhibit an anomaly behavior that differentiates them from normal AEVs, and thereby, the detection of anomalous AEVs and classification of anomaly type is required. Motivated from the aforementioned facts, the survey presents a systematic outlook of AI techniques in anomaly detection of AEVs. A solution taxonomy is proposed based on research gaps in the existing surveys, and the evaluation metrics for AI‐based anomaly detection are discussed. The open challenges and issues in AI deployments are discussed and a case study is presented on anomaly classification through a weighted ensemble technique. Thus, the proposed survey is designed to guide the manufacturing industry, AI practitioners, and researchers worldwide to formulate and design accurate and precise mechanisms to detect anomalies.
Bidirectional feedback between BCR signaling and actin cytoskeletal dynamics
Authors: Bhanja Anshuman , Rey‐Suarez Ivan , Song Wenxia , Upadhyaya Arpita
Published: June 2021

When B cells are exposed to antigens, they use their B‐cell receptors (BCRs) to transduce this external signal into internal signaling cascades and uptake antigen, which activate transcriptional programs. Signaling activation requires complex cytoskeletal remodeling initiated by BCR signaling. The actin cytoskeletal remodeling drives B‐cell morphological changes, such as spreading, protrusion, contraction, and endocytosis of antigen by mechanical forces, which in turn affect BCR signaling. Therefore, the relationship between the actin cytoskeleton and BCR signaling is a two‐way feedback loop. These morphological changes represent the indirect ways by which the actin cytoskeleton regulates BCR signaling. Recent studies using high spatiotemporal resolution microscopy techniques have revealed that actin also can directly influence BCR signaling. Cortical actin networks directly affect BCR mobility, not only during the resting stage by serving as diffusion barriers, but also at the activation stage by altering BCR diffusivity through enhanced actin flow velocities. Furthermore, the actin cytoskeleton, along with myosin, enables B cells to sense the physical properties of its environment and generate and transmit forces through the BCR. Consequently, the actin cytoskeleton modulates the signaling threshold of BCR to antigenic stimulation. This review discusses the latest research on the relationship between BCR signaling and actin remodeling, and the research techniques. Exploration of the role of actin in BCR signaling will expand fundamental understanding of the relationship between cell signaling and the cytoskeleton and the mechanisms underlying cytoskeleton‐related immune disorders and cancer.
Intelligent “Internet Plus” services in the first case of home hemodialysis in mainland China
Authors: Ni Zhaohui , Zhou Yijun , Lu Renhua , Shen Jianxiao , Zhao Li , Jin Haijiao , Zhang Haifen , Zhang Bin , Li Zhenyuan , Fang Yan , Fang Wei , Wang Qin , Gu Leyi , Zhang Weiming , Zhang Jidong , Mou Shan , Li Weiping
Published: June 2021

Background

Many studies have shown that compared with those who use other dialysis modalities, patients using home hemodialysis (HHD) have an increased rate of survival and better quality of life. It was noted in 2006 that there was opportunity for significant expansion of the use of HHD in many countries. China covers a vast area and has a large amount of end‐stage renal failure patients. But in mainland China, all dialysis treatments are in‐center, and the number of HHD patients is zero. In 2018, our hospital received the permission of the Shanghai government to carry out HHD.

Case presentation

We initiated four incident hemodialysis patients on an HHD regimen, one patient has been dialyzed in the home safely for 8 months. The biochemical parameters of the first patient remained stable on the regimen and he achieved standard Kt/V urea targets. Treatment‐related adverse events were not reported during the follow‐up. We combined HHD with intelligent “Internet Plus” real‐time remote monitoring and introduced the Internet, especially visualization software, to replace traditional telephone and home visit methods. It is more intuitive and quicker to assist patients in performing home hemodialysis and improve the safety of treatment.

Conclusions

HHD can be performed by selected trained patients in mainland China. Combined with the internet, visualization software, and traditional telephone and home visits, it is intuitive and quick to assist patients in carrying out HHD and improve the safety of treatment. HHD broadens the choices for uremia patients in China.
Comparison of the plaque regrowth inhibition effects of oil pulling therapy with sesame oil or coconut oil using 4‐day plaque regrowth study model: A randomized crossover clinical trial
Authors: Sezgin Yasemin , Memis Ozgul Betul , Maraş Muhammed Enes , Alptekin Nilgun Ozlem
Published: June 2021

Objectives

The aim of this study was to compare the plaque‐inhibiting effects of oil pulling therapy with sesame oil or coconut oil using 4‐day plaque regrowth study model.

Methods

This clinical observer‐masked, randomized, crossover designed study involved 24 participants. The participants received professional prophylaxis in the preparatory period and after that subjects started to use the allocated mouthrinse (coconut oil or sesame oil). On day 5, periodontal clinical parameters including plaque index (PI), gingival index (GI), stain index (SI) and bleeding on probing (BOP) were recorded. Subjects underwent a 14‐day wash out period and then used the other mouthrinse for 4 days.

Results

Oil pulling therapy with coconut oil or sesame oil exhibited similar plaque regrowth inhibition (PI = 1.60 ± 0.28 and 1.49 ± 0.22, for oil pulling with coconut oil and sesame oil, respectively) and tooth staining (SI = 0.20 ± 0.11 and 0.21 ± 0.09, for oil pulling with coconut oil and sesame oil, respectively.) In addition, GI and BOP were similar in both groups (GI = 0.61 ± 0.19 and 0.69 ± 0.16; BOP = 0.09 ± 0.24 and 0.03 ± 0.03 for oil pulling with coconut oil and sesame oil, respectively).

Conclusions

Oil pulling therapy with coconut or sesame oil showed similar results in terms of plaque regrowth inhibition and tooth staining. According to the present results, both coconut oil and sesame oil can be used for oil pulling therapy with the aim of plaque regrowth inhibition.
Erythropoiesis changes with increasing age in the elderly Chinese
Authors: Chen Si , Liu Yuan , Cai Lili , Ren Chunyun , Xiong Tie , Jin Ling , Nong Shaoyun , Chen Qian , Li Yao , Cong Yulong , Jiang Hong
Published: June 2021

Introduction

Erythropoiesis slowly decreases with increasing age, which may be reflected in red blood cell (RBC) parameters. This multicentre collaborative study aimed to investigate the changes in erythropoiesis with increasing age in a healthy Chinese population.

Methods

A total of 14,591 healthy individuals (6,713 aged at least 60 y and 7,878 aged below 60 y) from seven cities across China were enrolled. K2‐EDTA anticoagulant blood samples were analysed. The results are presented as median and 2.5‐97.5th percentile.

Results

RBC parameters showed some differences between the two groups divided by the age of 60 in the Chinese population. The median, 2.5th and 97.5th percentile values of RBC, haemoglobin (HGB) and haematocrit (HCT) in patients aged ≥ 60 y were significantly lower than in those ˂ 60 y. The values of mean cell volume (MCV), mean cell haemoglobin (MCH) and red cell distribution width (RDW) were higher in the group aged ≥ 60 y. Men had significantly higher RBC, HGB, HCT, MCV, MCH and RDW indices than women. The prevalence of anaemia gradually increased with age in men and was higher than that in women after 50. The median haemoglobin and MCV in Nanning and Guangzhou were lower than those in other regions.

Conclusion

RBC parameters varied with increasing age and differed between males and females, indicating that erythropoiesis decreases in the elderly Chinese population. Subsequent studies should be conducted for age‐ and sex‐specific reference intervals in healthy elderly Chinese populations.
Pension coverage in Latin America: Trends and inequalities
Authors: Mesa‐Lago Carmelo , Cruz Saco María Amparo , Gil Mirian
Published: June 2021

Using household surveys from 17 Latin American countries over 2009–2018, we analyze contributory pension coverage for the economically active population (EAP) and contributory/non‐contributory pension coverage for older persons. Nine countries have “private” and eight have “public” pension systems. Inequalities in gender, income, education, location and firm size affect both coverage of the EAP and the elderly. Rather than being affected by the type of pension system – private or public –, coverage depends on structural features of the labour market and public policy interventions. Our findings confirm current understanding that level of development is directly related with coverage whereas inequality and informality are inversely related with coverage. Based on these results, we recomend policy interventions.
Effects of interventions on rumination among individuals with cancer: A systematic review and meta‐analysis
Authors: Öcalan Sinem , Üzar‐Özçetin Yeter Sinem
Published: June 2021

Aim

This study aimed to examine the effects of interventions on rumination among individuals with cancer.

Design

A systematic review and meta‐analysis.

Data Sources

Six databases (Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), PsyArticles, CINAHL, PubMed and Web of Science) were searched for relevant articles published between January 2000 and April 2020.

Review methods

The findings of experimental studies (including both experimental and control groups) related to interventions to effect rumination of individuals with cancer were included. Comprehensive meta‐analysis was used to analyse the data. Hedges’ g and 95% confidence intervals (CIs) were computed to estimate the effect. Additionally, funnel plots were created and heterogeneity was analysed using the I2 test. The Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) was used.

Results

Eight studies, which included a total sample of 856 individuals with cancer, were included. Half of the studies (n = 4) were randomised controlled trials, and six of them had conducted mindfulness‐based interventions. The interventions had significant effects on rumination among individuals with cancer (z = −2.356, Q = 167.663, p < 0.001, I2 = 95.825%). The effect size was −0.894 (95% CI = [−1.638, −0.150]) and statistically significant (p < 0.001).

Conclusion

The interventions had reduced rumination among individuals with cancer. These effects should be interpreted with caution because there was a high level of heterogeneity. However, only a few studies were included, and the findings underscore the need for further research.

Impact

Many individuals are likely to benefit from rumination‐focused interventions, especially mindfulness‐based interventions. Nurses should utilise available opportunities to facilitate the optimal management of cancer‐related rumination.
A Criminal Law for Semicitizens
Authors: Coca‐Vila Ivó , Irarrázaval Cristián
Published: June 2021

A significant number of influential philosophical theorists of punishment argue that only those who enjoy the status of citizenship in a political community can legitimately be punished by that polity. Yet, the strength of this approach wanes when these scholars treat individuals who clearly do not respond to their idealised conception of citizenship (such as asylum seekers, disenfranchised offenders, and tourists) as if they were fully fledged citizens. This article argues that ‘citizen criminal law’ can only be theoretically feasible in today's world if it abandons the binary position between ‘full citizens’ and ‘noncitizens’ and recognises the everlasting presence of certain types of ‘semicitizens’. Thus, citizenship should be conceived as a scalar phenomenon. Based on a typological approach to the different forms of semicitizenship, we argue that the strength of the political bond between offenders and the political community must be considered when gauging punishment severity. The weaker the bond, the more lenient the punishment should be.