bluuebunny/crossref_metadata_2025 huggingface dataset:
Hexagonal Skin Excision in Lipoabdominoplasty Aiming for a Smaller Scar and Efficient Waist
Authors: Tallal Raghda E. , Estawrow Mina A. , Reyad Khaled A.
Published: June 2022

Standard abdominoplasty scars may extend beyond the boundaries of the abdomen. Contemporary styles of body exposure and bathing suits demand that those incisions be hidden inside the “bikini line.” Although a smaller incision used for a mini abdominoplasty might be confined to the abdomen, larger incisions to remove massive amounts of fat and skin excess from the abdomen routinely require extensions toward the groin or iliac areas. Preoperative marking of the incision in an abdominoplasty procedure plays a key role in the shape, length, and position of the resulting scar. Undermining, traction, and resection of redundant tissue also influence these outcomes; therefore, we aim to standardize the abdominoplasty excision pattern. A uniform hexagon design for skin excision was used in 22 patients, with measures that may be used universally, for all patients with moderate skin redundancy. The design was applied successfully to decrease the ultimate scar width, and asymmetry and increase waist definition. All patients’ wounds healed uneventfully. The scar width in all patients did not cross the mid-axillary line. The scar was shorter than the standard abdominoplasty scar that may extend beyond the mid-axillary line. This hexagonal pattern of skin excision provides a quick and consistent technique for skin excision and resultant shorter scar.
Loss of Lower Eyelid Bulge after the Reconstruction of Zygomatic Complex Fractures
Authors: Uemura Kazuhisa , Shirakawa Yuji , Nishioka Toshihiko , Wada Yoshitaka , Yamada Gen , Asamura Shinichi
Published: June 2022

Background:

Surgery for zygomatic complex fractures primarily aims to obtain facial symmetry. We investigated facial symmetry specific to lower eyelid bulges following zygomatic complex fractures approached through the lower eyelid.

Methods:

Forty-one consecutive patients underwent treatment of zygomatic complex fractures by swinging eyelid approach or subciliary approach. In both approaches, the periosteum was incised 2 mm caudal to the inferior orbital rim and the orbicularis retaining ligament (ORL) was released. The orbital rim periosteum was interruptedly sutured and reconstruction of the orbital septum or ORL was not performed at the time of closure. In cases with a lower eyelid bulge on the nonfractured side, in a frontal photograph 6 months after the operation, the degree of loss of the lower eyelid bulge on the fractured side was classified as either “none,” “mild,” or “severe.”

Results:

Lower eyelid bulge was present on the nonfractured side in 19 of 41 patients, all of whom were over 50 years old. Loss of lower eyelid bulge was observed on the fractured side in all cases: 15 cases following the swinging eyelid approach (mild/severe; 6/9) and four cases following the subciliary approach (mild/severe; 2/2).

Conclusions:

In reconstruction after zygomatic complex fractures, lower eyelid bulges were lost in both the swinging eyelid and subciliary approaches in patients over 50 years old. The cause was thought to be an ORL release or an unintended septal reset-like effect.
What cardiologists should know about cardiac sarcoidosis in 2022?
Authors: Lemay Sylvain , Marchand Laurie , Sénéchal Mario
Published: June 2022

Purpose of review

Cardiac sarcoidosis (CS) is a potentially fatal condition when unrecognized or not treated adequately. The purpose of this review is to provide new strategies to increase clinical recognition of CS and to present an updated overview of the immunosuppressive treatments using most recent data published in the last 18 months.

Recent findings

CS is an increasingly recognized pathology, and its diagnostic is made 20 times more often in the last two decades. Recent studies have shown that imaging alone usually lacks specificity to distinguish CS from other inflammatory cardiomyopathies. However, imaging can be used to increase significantly diagnostic yield of extracardiac and cardiac biopsy. Recent reviews have also demonstrated that nearly 25% of patients will be refractory to standard treatment with prednisone and that combined treatment with a corticosteroid-sparing agent is often necessary for a period that remains undetermined.

CS is a complex pathology that should always require a biopsy attempt to have a histological proven diagnosis before starting immunosuppressive therapy consisting of corticosteroids with or without a corticosteroid-sparing agent.
Electronic health strategies to improve medication adherence in patients with cardiometabolic disease: current status and future directions
Authors: Peacock Erin , Craig Leslie S. , Krousel-Wood Marie
Published: June 2022

Purpose of review

Enabled by widespread technological advancements, electronic health (eHealth) strategies have expanded rapidly over the last decade, presenting opportunities to support self-management including medication adherence for cardiometabolic disease control. eHealth can minimize access barriers to medications, enable timely assessment and shared decision-making, and provide medication reminders and health data feedback. This review summarizes current evidence for effectiveness of eHealth strategies for improving medication adherence in patients with hypertension, type 2 diabetes, and/or hyperlipidemia, and identifies priorities for future research.

Recent findings

Current research supports the effectiveness of eHealth strategies to improve medication adherence and clinical outcomes for cardiometabolic disease. Although patient acceptability of eHealth strategies is generally high, engagement may decline over time. In addition, differences in effectiveness across intervention characteristics and sociodemographic groups are understudied, limiting generalizability and tailoring of interventions to local health system resources, culture, and patient needs or preferences.

eHealth is a promising tool for addressing low medication adherence. Further work incorporating rigorous evaluation, assessment of patient engagement over time and effectiveness of intervention characteristics and components, and a health equity lens addressing eHealth use in vulnerable groups will increase understanding of the full potential of eHealth for improving medication adherence in diverse patients with cardiometabolic disease.
RNA interference-based therapies for the control of atherosclerosis risk factors
Authors: Kettunen Sanna , Ruotsalainen Anna-Kaisa , Ylä-Herttuala Seppo
Published: June 2022

Purpose of review

Atherosclerosis, characterized by lipid accumulation and chronic inflammation in the arterial wall, is the leading causes of death worldwide. The purpose of this article is to review the status of RNA interference (RNAi) based therapies in clinical trials for the treatment and prevention of atherosclerosis risk factors.

Recent findings

There is a growing interest on using RNAi technology for the control of atherosclerosis risk factors. Current clinical trials utilizing RNAi for atherosclerosis are targeting lipid metabolism regulating genes including proprotein convertase subtilisin/kexin 9, apolipoprotein C-III, lipoprotein (a) and angiopoietin-like protein 3. Currently, three RNAi-based drugs have been approved by U.S. Food and Drug Administration, but there are several therapies in clinical trials at the moment, and potentially entering the market in near future. In addition, recent preclinical studies on regulating vascular inflammation have shown promising results.

In recent years, RNAi based technologies and therapies have been intensively developed for the treatment of atherosclerosis risk factors, such as hyperlipidemia and vascular inflammation. Multiple potential therapeutic targets have emerged, and many of the reported clinical trials have already been successful in plasma lipid lowering. The scope of RNAi therapies is well recognized and recent approvals are encouraging for the treatment of cardiovascular and metabolic disorders.
Role of plasma extracellular vesicles in prediction of cardiovascular risk and alterations in response to statin therapy in hypertensive patients
Authors: Oggero Silvia , Godec Thomas , van Gorp Rick , Pinto Adreia L. , Schurgers Leon J. , Reutelingsperger Chris , Sever Peter , Norling Lucy V. , Perretti Mauro , Gupta Ajay
Published: June 2022

Background:

Rapid and accurate new biomarkers to predict risk of cardiovascular disease (CVD) are essential. The utility of extracellular vesicles in predicting the CVD risk is postulated, yet it remains unknown whether their expression is altered in response to statin therapy.

Methods:

We performed in-vitro studies with human umbilical vein endothelial cells (HUVEC) and vascular smooth muscle cells (hVSMC), and conducted a nested case–control study (nCCS) in hypertensive patients (n = 40) randomized to either atorvastatin or placebo in the ASCOT-LLA. Cases had a major adverse cardiovascular event or death (MACE) during 3.5 years of follow-up (median) from the time of extracellular vesicle characterization while controls, matched for age and duration of treatment, remained event-free. Conditional logistic regression models determined the risk of MACE. Additionally, the relationship of extracellular vesicle levels with statin therapy was assessed.

Results:

Added to HUVEC, extracellular vesicles increased neutrophil recruitment, and to hVSMC, aggravated calcification and proliferation. In the nCCS, compared with controls, cases (i.e. with MACE) had preceding higher levels of CD14+ and CD14+/CD41+ extracellular vesicles (P = 0.009 and P = 0.012, respectively) and a significant reduction in the median size of the vesicles (P = 0.037). On matched analysis, higher CD14+ extracellular vesicles were associated with a 3.7-fold increased risk of MACE (P = 0.032). Patients treated with atorvastatin (vs. placebo) had both reduced size of extracellular vesicles and the proportion of CD146+ extracellular vesicles (P = 0.034 and P = 0.020, respectively).

Conclusion and relevance:

These pilot analyses suggest a mechanistic role for extracellular vesicles in the development of CVD, with significant and differential changes in extracellular vesicles amongst those at risk of MACE, and those on atorvastatin therapy.
The Impact of Thyroid Diseases on Patients' Work Functioning
Authors: Vetrani Ilaria , Leso Veruscka , Fontana Luca , Vetrani Claudia , Spadarella Emanuela , Sessa Francesca , Porcelli Tommaso , Iavicoli Ivo
Published: June 2022

Objective

This study aimed to investigate the impact of thyroid diseases (TDs) on patients' work ability (WA) and related influencing factors.

Methods

A total of 150 TD workers and matched healthy controls were enrolled from May 2020 to November 2021. The Work Ability Index was used to assess the workers' perception of WA.

Results

Overall, TD workers reported a good WA, although with a significantly lower mean score compared with controls (39 ± 6 vs 43 ± 4, P < 0.001). Subjects with Graves disease and follicular carcinoma showed the worst WA perception. Suffering from a TD (β = −0.396, P < 0.001) and job duration (β = −0.173, P < 0.001) were associated with poorer WA.

Conclusions

Better understanding the impact that TD may have on work functioning can inform an interdisciplinary management of TD workers to support their personal, social, and professional lives.
Digital Reading with Low Vision: Principles for Selecting Display Size
Authors: Xiong Ying-Zi , Atilgan Nilsu , Fletcher Donald C. , Legge Gordon E.
Published: June 2022

SIGNIFICANCE

Digital reading devices have become increasingly popular among people with low vision. Because displays come in many sizes ranging from smart watches to large desktop computer displays, it is important to have principles to guide people with low vision in selecting suitable displays for reading.

PURPOSE

The selection of effective digital displays for reading by people with low vision focuses attention on the interacting effects of print size, display size, font, visual acuity, and reading distance. This technical report aims to provide principles for identifying the minimum size of digital displays required for fluent reading by people with low vision.

METHODS

We emphasize two critical factors in selecting an appropriate reading display: angular print size, which should exceed the individual's critical print size, and display size, which should allow at least 13 characters to be presented on each line. Our approach considers a low-vision individual's acuity and preferences for viewing distance and fonts.

RESULTS

Through an illustrative example, we demonstrate how our approach can be used to determine display size for a low-vision individual with 20/200 acuity and central field loss who wants to read at 30-cm viewing distance with the Times Roman font. We have developed a web application based on our recommended approach to provide easy access to our algorithm.

CONCLUSIONS

We provide a procedure to guide the selection of appropriate displays for a wide range of acuities. Our approach can help clinicians in making recommendations for their patients, digital product designers in developing more accessible devices, and low-vision individuals in selecting digital displays for reading.
Hormone therapy and fractures in postmenopausal women
Authors: Yin Michael T. , Hoover Donald R. , Shi Qiuhu , Tien Phyllis C. , Cohen Mardge H. , Kassaye Seble , Gustafson Deborah , Adimora Adaora , Weitzmann M. Neale , Bolivar Hector , Warriner Amy , Bares Sara H. , Sharma Anjali
Published: June 2022

Background:

Fracture rates have been reported to be higher among older women living with HIV (WLWH) than HIV− women. Hormone therapy with estrogen can reduce vasomotor symptoms (VMS) associated with menopause and prevent fractures. As data are limited on the benefits of hormone therapy use in WLWH, we examined associations of hormone therapy, use and fractures.

Methods:

A prospective study of 1765 (1350 WLWH and 415 HIV−) postmenopausal Women's Interagency HIV Study (WIHS) participants was performed, including self-reported hormone therapy, use and fracture data from 2003 to 2017. Proportional hazard models determined predictors of new fractures at any site or at typical fragility fracture sites (hip, spine, wrist).

Results:

At the first postmenopausal visit, the median (IQR) age of WLWH was slightly younger than HIV− women [49.8 (46.4–53) vs. 50.7 (47.5–54), P = 0.0002] and a smaller proportion of WLWH reported presence of VMS (17% vs. 26%, P < 0.0001). A greater proportion of WLWH than HIV− women reported hormone therapy use (8% vs. 4%, P = 0.007) at the first postmenopausal visit. In multivariate analyses, white race and smoking were significant predictors of incident fracture at any site but hormone therapy (P = 0.69) and HIV status (P = 0.53) were not.

Conclusion:

Our study did not find evidence of benefit or harm with regards to fracture outcomes in postmenopausal WLWH receiving hormone therapy. Further research is needed to determine whether hormone therapy has benefits beyond treatment of VMS, such as prevention of adverse aging-associated outcomes.
Foraging behaviour and patch size distribution jointly determine population dynamics in fragmented landscapes
Authors: Nauta Johannes , Simoens Pieter , Khaluf Yara , Martinez-Garcia Ricardo
Published: June 2022

Increased fragmentation caused by habitat loss represents a major threat to the persistence of animal populations. How fragmentation affects populations depends on the rate at which individuals move between spatially separated patches. Whereas negative effects of habitat loss on biodiversity are well known, the effects of fragmentation
per se
on population dynamics and ecosystem stability remain less well understood. Here, we use a spatially explicit predator–prey model to investigate how the interplay between fragmentation and optimal foraging behaviour affects predator–prey interactions and, subsequently, ecosystem stability. We study systems wherein prey occupies isolated patches and are consumed by predators that disperse following Lévy random walks. Our results show that the Lévy exponent and the degree of fragmentation jointly determine coexistence probabilities. In highly fragmented landscapes, Brownian and ballistic predators go extinct and only scale-free predators can coexist with prey. Furthermore, our results confirm that predation causes irreversible habitat loss in fragmented landscapes owing to overexploitation of smaller patches of prey. Moreover, we show that predator dispersal can reduce, but not prevent or minimize, the amount of lost habitat. Our results suggest that integrating optimal foraging theory into population and landscape ecology is crucial to assessing the impact of fragmentation on biodiversity and ecosystem stability.
Impact of contact data resolution on the evaluation of interventions in mathematical models of infectious diseases
Authors: Contreras Diego Andrés , Colosi Elisabetta , Bassignana Giulia , Colizza Vittoria , Barrat Alain
Published: June 2022

Computational models offer a unique setting to test strategies to mitigate the spread of infectious diseases, providing useful insights to applied public health. To be actionable, models need to be informed by data, which can be available at different levels of detail. While high-resolution data describing contacts between individuals are increasingly available, data gathering remains challenging, especially during a health emergency. Many models thus use synthetic data or coarse information to evaluate intervention protocols. Here, we evaluate how the representation of contact data might affect the impact of various strategies in models, in the realm of COVID-19 transmission in educational and work contexts. Starting from high-resolution contact data, we use detailed to coarse data representations to inform a model of SARS-CoV-2 transmission and simulate different mitigation strategies. We find that coarse data representations estimate a lower risk of superspreading events. However, the rankings of protocols according to their efficiency or cost remain coherent across representations, ensuring the consistency of model findings to inform public health advice. Caution should be taken, however, on the quantitative estimations of those benefits and costs triggering the adoption of protocols, as these may depend on data representation.
Drosophilaimmunity: theDrosocingene encodes two host defence peptides with pathogen-specific roles
Authors: Hanson M. A. , Kondo S. , Lemaitre B.
Published: June 2022

Antimicrobial peptides (AMPs) are key to defence against infection in plants and animals. Use of AMP mutations inDrosophilahas now revealed that AMPs can additively or synergistically contribute to defencein vivo. However, these studies also revealed high specificity, wherein just one AMP contributes an outsized role in combatting a specific pathogen. Here, we show theDrosocinlocus (CG10816) is more complex than previously described. In addition to its namesake peptide ‘Drosocin’, it encodes a second mature peptide from a precursor via furin cleavage. This peptide corresponds to the previously uncharacterized ‘Immune-induced Molecule 7’. A polymorphism (Thr52Ala) in the Drosocin precursor protein previously masked the identification of this peptide, which we name ‘Buletin’. Using mutations differently affecting Drosocin and Buletin, we show that only Drosocin contributes toDrosocingene-mediated defence againstEnterobacter cloacae. Strikingly, we observed that Buletin, but not Drosocin, contributes to theDrosocingene-mediated defence againstProvidencia burhodogranariea, including an importance of the Thr52Ala polymorphism for survival. Our study reveals that theDrosocingene encodes two prominent host defence peptides with different specificity against distinct pathogens. This finding emphasizes the complexity of theDrosophilahumoral response and demonstrates how natural polymorphisms can affect host susceptibility.
Trends in telehealth use by Medicare fee-for-service beneficiaries and its impact on overall volume of healthcare services
Authors: Ellimoottil Chad , Zhu Ziwei , Dunn Rodney L. , Thompson Michael P.
Published: June 2022

Introduction

At the start of the COVID-19 public health emergency, the federal government made temporary Medicare policy changes to expand telehealth coverage, resulting in a surge in telehealth use. As federal and state policymakers currently consider permanent telehealth policy options, it is important to understand the trends in telehealth use during 2021 and whether telehealth has led to an increase in the overall volume of healthcare services.

Methods

Our analysis was conducted using Part B claims for 100% of Medicare fee-for-service beneficiaries. We identified all outpatient evaluation and management (E&M) services received by beneficiaries from January 1, 2019 through December 31, 2021. We then calculated the monthly proportion of outpatient E&M services that were performed in-person and through telehealth.

Results

The total number of all outpatient E&M services was 289.0 million in 2019, 255.2 million in 2020 (11.7% lower than 2019), and 260.7 million in 2021 (9.8% lower than 2019). Monthly telehealth services peaked at 7.2 million (or 50.7% of monthly E&M services) in April 2020, followed by a slow decline through the end of 2021. During the second half of 2021, telehealth services made up 8.5-9.5% of monthly E&M services.

Conclusion

From April 2020 through December 2021, the monthly volume of telehealth services slowly declined and has plateaued between 8.5-9.5% of all outpatient E&M services received by Medicare fee-for-service beneficiaries. Importantly, the total volume of outpatient E&M services was lower in 2020 and 2021, suggesting that the COVID-19 telehealth flexibilities have not increased the overall volume of outpatient E&M services received by Medicare beneficiaries. These findings should mitigate some concerns about the impact of telehealth on overall healthcare utilization.

At the start of the COVID-19 public health emergency, the federal government made temporary Medicare policy changes to expand telehealth coverage, resulting in a surge in telehealth use.1,2 While telehealth was a necessary substitute for in-person care during first few months of the pandemic, there was a decline in the use of telehealth during the second half of 2020.3 As federal and state policymakers currently consider permanent telehealth policy options, it is important to understand the trends in telehealth use during 2021 and whether telehealth has led to an increase in the overall volume of healthcare services.
Deep-Learning-Based Generation of Synthetic High-Resolution MRI from Low-Resolution MRI for Use in Head and Neck Cancer Adaptive Radiotherapy
Authors: Wahid Kareem A. , Xu Jiaofeng , El-Habashy Dina , Khamis Yomna , Abobakr Moamen , McDonald Brigid , O’Connell Nicolette , Thill Daniel , Ahmed Sara , Sharafi Christina Setareh , Preston Kathryn , Salzillo Travis C , Mohamed Abdallah , He Renjie , Cho Nathan , Christodouleas John , Fuller Clifton D. , Naser Mohamed A.
Published: June 2022

Background

Quick, low contrast resolution magnetic resonance imaging (MRI) scans are typically acquired for daily MRI-guided radiotherapy setup. However, for patients with head and neck (HN) cancer, these images are often insufficient for discriminating target volumes and organs at risk (OARs). In this study, we investigated a deep learning (DL) approach to generate high-resolution synthetic images from low-resolution images.

Methods

We used 108 unique HN image sets of paired 2-minute T2-weighted scans (2mMRI) and 6-minute T2-weighted scans (6mMRI). 90 image sets (∼20,000 slices) were used to train a 2-dimensional generative adversarial DL model that utilized 2mMRI as input and 6mMRI as output. Eighteen image sets were used to test model performance. Similarity metrics, including the mean squared error (MSE), structural similarity index (SSIM), and peak signal-to-noise ratio (PSNR) were calculated between normalized synthetic 6mMRI and ground-truth 6mMRI for all test cases. In addition, a previously trained OAR DL auto-segmentation model was used to segment the right parotid gland, left parotid gland, and mandible on all test case images. Dice similarity coefficients (DSC) were calculated between 2mMRI and either ground-truth 6mMRI or synthetic 6mMRI for each OAR; two one-sided t-tests were applied between the ground-truth and synthetic 6mMRI to determine equivalence. Finally, a Turing test using paired ground-truth and synthetic 6mMRI was performed using three clinician observers; the percentage of images that were correctly identified was compared to random chance using proportion equivalence tests.

Results

The median similarity metrics across the whole images were 0.19, 0.93, and 33.14 for MSE, SSIM, and PSNR, respectively. The median of DSCs comparing ground-truth vs. synthetic 6mMRI auto-segmented OARs were 0.84 vs. 0.83, 0.82 vs. 0.82, and 0.80 vs. 0.83 for the right parotid gland, left parotid gland, and mandible, respectively (equivalence p<0.05 for all OARs). The percent of images correctly identified was equivalent to chance (p<0.05 for all observers).

Conclusions

Using 2mMRI inputs, we demonstrate that DL-generated synthetic 6mMRI outputs have high similarity to ground-truth 6mMRI. Our study facilitates the clinical incorporation of synthetic MRI in MRI-guided radiotherapy.
Emotions in the time of COVID-19: A sentiment analysis of tweets during the nationwide lockdown in India
Authors: Abdulkader Rizwan Suliankatchi , Jeyashree Kathiresan , Venugopal Deneshkumar , Kannan K Senthamarai , Ponnaiah Manickam , Murhekar Manoj
Published: June 2022

Background

COVID-19 pandemic is unprecedented in terms of burden, nature and quantum of control measures and public reactions. We report trends in public emotions and sentiments before and during the nation-wide lockdown implemented since 25th March 2020 in India.

Methods

We collected a sample of tweets containing the keywords ‘coronavirus’ or ‘COVID-19’ published between 12th March and 14th April in India. After pre-processing, the tweets were subjected to sentiment analysis using natural language processing algorithms.

Results

Our analysis of 226170 tweets revealed a positive public sentiment (mean sentiment score=0.25). Tweets expressing a given sentiment showed significant (p<0.001) waning of negativity; negative tweets decreased (39.3% to 35.9%) and positive tweets increased (49.8% to 51.8%). Trust (0.85 words/tweet/day) and fear (0.66 words/tweet/day) were the dominant positive and negative emotions, respectively.

Conclusions

Positive sentiments dominated during the COVID-19 lockdown in India. A surveillance system monitoring public sentiments on public health interventions for COVID-19 should be established.
Complicated Common Variable Immunodeficiency is Driven by Aberrant IL-10/IL-21 Signaling and Predisposed Polygenic Risk
Authors: Khan Humza A. , Acar Utkucan , Stephens Alexis V. , Thauland Timothy J. , Butte Manish J.
Published: June 2022

Background

The inborn errors of immunity (IEI) that include defective antibody responses are clinically heterogenous, especially the common variable immunodeficiency (CVID) phenotype that includes low immunoglobulin levels and impaired humoral responses to antigens. Beyond recurrent infections, many with the CVID phenotype develop non-infectious complications (NICs), including autoimmunity and lymphoproliferation, that confer a high rate of morbidity and mortality. At present, it is unknown what genetic and functional factors predispose patients to NICs.

Objective

We aimed to discover the pathobiology underlying complicated CVID (CVIDc).

Methods

In a heterogenous group of 12 CVIDc patients, we conducted whole exome sequencing and high-throughput signaling assays by multiplexed phospho-mass cytometry. The immune deficiency and dysregulation activity (IDDA) score was used to determine the burden of NICs in individual patients. We integrated polygenic risk scores to determine the role of common background variants in the pathogenesis of CVIDc.

Results

In CVID patients with high IDDA scores, there was aberrant increased phosphorylation of STAT1 and STAT3 upon stimulation with IL-10 or IL-21. Furthermore, common variants related to high eosinophil count and allergy/eczema confer a higher likelihood of autoimmunity in CVID.

Conclusion

Variants in loci related to high eosinophil count/function and over-reactive IL-10 signaling are associated with the development of autoimmune disease and NICs in CVID.

Clinical implications

It may be possible to manage CVIDc through modulating IL-10 and IL-21 signaling pathways. Polygenic risk scoring may predict the development of autoimmune complications in CVID patients.
Agent-based vs. equation-based multi-scale modeling for macrophage polarization
Authors: Minucci Sarah B. , Heise Rebecca L. , Reynolds Angela M.
Published: June 2022

Macrophages show high plasticity and result in heterogenic subpopulations or polarized states identified by specific cellular markers. These immune cells are typically characterized as pro-inflammatory, or classically activated M1, and anti-inflammatory, or alternatively activated M2. However, a more precise definition places them along a spectrum of activation where they may exhibit a number of pro- or anti-inflammatory roles. To gain a greater understanding of the mechanisms of the immune response from macrophages and the balance between M1 and M2 activation, we utilized two different modeling techniques, ordinary differential equation (ODE) modeling and agent-based modeling (ABM), to simulate the spectrum of macrophage activation to general pro- and anti-inflammatory stimuli on an individual and multi-cell level. The ODE model includes two hallmark pro- and anti-inflammatory signaling pathways and the ABM incorporates similar M1-M2 dynamics but in a spatio-temporal platform. Both models link molecular signaling with cellular-level dynamics. We then performed simulations with various initial conditions to replicate different experimental setups. Similar results were observed in both models after tuning to a common calibrating experiment. Comparing the two models’ results sheds light on the important features of each modeling approach. When more data is available these features can be considered when choosing techniques to best fit the needs of the modeler and application.
Chronic cardiotoxicity assessment by cell optoporation on microelectrode arrays
Authors: Iachetta Giuseppina , Melle Giovanni , Colistra Nicolò , Tantussi Francesco , De Angelis Francesco , Dipalo Michele
Published: June 2022

The reliable identification of chronic cardiotoxic effects in in vitro screenings is fundamental for filtering out toxic molecular entities before in vivo animal experimentation and clinical trials. Present techniques such as patch-clamp, voltage indicators, and standard microelectrode arrays do not offer at the same time high sensitivity for measuring transmembrane ion currents and low-invasiveness for monitoring cells over long time. Here, we show that optoporation applied to microelectrode arrays enables measuring action potentials from human-derived cardiac syncytia for more than 1 continuous month and provides reliable data on chronic cardiotoxic effects caused by known compounds such as pentamidine. The technique has high potential for detecting chronic cardiotoxicity in the early phases of drug development.
Optimal linear estimation models predict 1400-2800 years of co-existence between Neandertals and Homo sapiens in western Europe
Authors: Djakovic Igor , Key Alastair , Soressi Marie
Published: June 2022

Recent fossil discoveries suggest that Neandertals and Homo sapiens may have co-existed in Europe for as long as five to six thousand years. Yet, evidence for their contemporaneity at any regional scale remains elusive. In France and northern Spain, a region which features some of the latest directly-dated Neandertals in Europe, Protoaurignacian assemblages attributed to Homo sapiens appear to ‘replace’ Neandertal-associated Châtelperronian assemblages. Using the earliest and latest known occurrences as starting points, Bayesian modelling has provided some indication that these occupations may in fact have been partly contemporaneous. The reality, however, is that we are unlikely to ever identify the ‘first’ or ‘last’ appearance of a species or cultural tradition in the archaeological and fossil record. Here, we use optimal linear estimation modelling to estimate the first appearance date of Homo sapiens and the extinction date of Neandertals in France and northern Spain by statistically inferring these ‘missing’ portions of the Protoaurignacian and Châtelperronian archaeological records. Additionally, we estimate the extinction date of Neandertals in this region using a set of directly-dated Neandertal fossil remains. The results suggest that the onset of the Homo sapiens occupation of this region likely preceded the extinction of Neandertals and the Châtelperronian by up to 1400-2900 years – raising the possibility of an extended co-existence of these groups during the initial Upper Palaeolithic of this region. Whether or not this co-existence featured some form of direct interaction, however, remains to be resolved.
Transmission potential of human monkeypox in mass gatherings
Authors: Sypsa Vana , Mameletzis Ioannis , Tsiodras Sotirios
Published: June 2022

Since May 2022, a large number of monkeypox cases has been reported in non-endemic settings. Taking into account the strict measures implemented due to the COVID-19 pandemic and the desire of people to reclaim what is perceived as lost time, it is anticipated that mass gatherings this summer will be highly attended. Based on data for the secondary attack rate among unvaccinated contacts from endemic countries, we estimate that, on average, more than one secondary case is anticipated per infectious person if he/she has a high number of group contacts (>30) or more than eight close contacts. Although the role of group contacts in mass gatherings is uncertain (less likely to involve physical contact, shorter duration), close contacts associated with the event (e.g. intimate/sexual contact with other attendees) might be the amplifying event. Enforcing awareness, early recognition and engaging affected populations in the monkeypox response are important to control transmission.
Non-catastrophic collapse of VEEV by lethal mutagenesis
Authors: Alejandro Brian , Kim Eun Jung , Hwang Jae Yeon , Park Juw Won , Smith Melissa , Chung Donghoon
Published: June 2022

RNA viruses replicate at a high mutation rate, providing a highly adaptive capacity to the population as well as vulnerability to an extinction due to additional mutations, which is the conceptual basis for lethal mutagenesis. However, the mechanistic understanding of lethal mutagenesis has remained unclear due to the lack of RNA mutagens with potent antiviral activity and the inherent inability to distinguish between infectious and non-infectious sub-populations within a viral population. In our study, we investigated how the replication competency and mutation frequency of Venezuelan Equine Encephalitis Virus (VEEV) change following treatment with the RNA mutagen β-d-N4-hydroxycytidine, a potent antiviral RNA mutagen. By pairing limiting dilution with a long-read sequencing approach, we specifically determined genomic sequences of replication-competent viral clones from the total population. We found that replication-competent VEEV population maintained itself within a narrow mutation spectrum with a significantly lower mutation frequency than the total population. We also found that treatment with an RNA mutagen did not induce catastrophic destruction of the infectious population even at a high exposure, allowing replication-competent subpopulations with increased variability in mutational fitness and enhanced adaptability to new selection pressures, such as antiviral treatment, to continue to propagate. Together our study provides new understanding of viral population landscape and suggests a careful consideration of lethal mutagenesis as an antiviral strategy for high-capacity replicating viruses such as alphaviruses.
Optimization for Predictive Gene Circuit Design Automation
Authors: Starkey Frederick , Menolascina Filippo
Published: June 2022

Synthetic Biology aims to rationally engineer biological systems. Current methods often employ an initial human designed circuit topology and utilise iterative approaches, e.g. directed evolution, to fine-tune part function. This approach can be extremely time consuming and resource intensive whilst often reaching sub-optimal solutions. A design workflow in which circuits and parts are designed in silico can overcome such limitations. Here we describe a method to automatically design synthetic gene circuits with user-specified dynamics; unlike some previous contributions our algorithm is able to design circuits with analog, not just digital behaviours. We demonstrate the capabilities of our approach benchmarking it on a number of different gene circuits design tasks. We review and compare the performance of our method against state of the art and outline future opportunities for development. Finally, to foster adoption, we make our algorithm available through a web app.
Barriers to adopting integrated project delivery practices
Authors: Ma Qiuwen , Li Shan , Teo Pei Xin , Ling Florence Yean Yng
Published: June 2022

Purpose

Compared with traditional approaches, integrated project delivery (IPD) improves project performance by enhancing integration. To adopt IPD, however, existing practices need to be changed, which creates barriers to implementation. This study aims to identify the barriers to IPD practices in China and Singapore, whose practitioners show different types and levels of integration experience.

Design/methodology/approach

A questionnaire survey was administered to two groups of respondents: Chinese and Singaporean. The data were analyzed using three nonparametric techniques, including Wilcoxon signed-rank test, Mann-Whitney-Wilcoxon test, and Spearman rank correlation.

Findings

(1) Of 39 possible barriers, 36 were consistently felt by both Chinese and Singaporean practitioners with different backgrounds; (2) The Chinese group perceived more issues to be significant barriers than the Singaporean group; (3) The Singaporean group had more experience than the Chinese group in performing integration in five areas. This lessens some barriers to adopting IPD practices.

Originality/value

This study is important because it uncovers barriers to the effective implementation of IPD and shows the importance of certain types and levels of integration experience in overcoming these barriers. The results will be useful to practitioners planning to adopt IPD in China or Singapore.
Supply chain relational capital and firm performance: an empirical enquiry from India
Authors: Pant Pushpesh , Dutta Shantanu , Sarmah S.P.
Published: June 2022

Purpose

The purpose of this paper is to examine how over-reliance on buyer-supplier relational capital (created through the interconnected supply chain and social network) impacts firm performance in the context of the emerging market, i.e. India.

Design/methodology/approach

The study uses the Prowess database (on Indian firms) to identify the firms that rely heavily on relational capital and employs panel data regression analyses to test the effect of relational capital on firm performance (supply chain performance and financial performance).

Findings

The results show that over-reliance on relational capital leads to lower supply chain performance (proxied by supply chain cycle) and financial performance (proxied by Tobin's Q). The results also reveal that supply chain performance mediates the relationship between over-reliance on relational capital and financial performance. Together, these results indicate that over-reliance on relational capital created through the interconnected supply chain and social network for supply chain management may negatively affect a firm's competitive advantage, which in turn can significantly impede its financial performance.

Originality/value

In light of the supply chain literature and relevant theories, the study develops an objective understanding of over-reliance relational capital created through the interconnected supply chain and social network, by relying on a large panel dataset of manufacturing firms and hence contributes to the supply chain literature. Also, it presents a novel idea to operationalize the measure for relational capital using the Prowess database.
Financial integration and capital structure decisions of listed firms: evidence from China
Authors: Ahmed Ahsan , Zainudin Rozaimah , Shaharuddin Shahrin Saaid
Published: June 2022

Purpose

This paper investigates the impact of financial integration on the capital structure of the firms operating in mainland China, examining the firm-level and country-level integrating variables for 2,878 listed Chinese firms over the period of 1991–2016 in regard to the firms' capital structures. Finally, the study revisits the associations for the state-owned and multinational firms in the context of China.

Design/methodology/approach

A large sample of unbalanced data from firms were used to explore the relationship firm-level and country-level integrating variables has with firm leverage and maturity; this is accomplished using the fixed effect model. For robustness, a system-generalised method of moments was used.

Findings

The results indicate that internationalisation positively impacts the leverage and debt maturity of all listed Chinese firms and multinational firms and that state-owned firms are financed mainly by the state. For country-level integration, the authors find that credit and equity markets are negatively related to a firm's leverage. A negative relation with credit markets suggests that Chinese firms have much cheaper financing options than the benefits that arise from credit market integration. Moreover, the effect of equity market integration is more pronounced on Chinese firms' capital structure and debt maturity than credit market integration.

Practical implications

The results provide valuable implications of financial integration for policymakers as well as capital structure decision-making for managers in China.

Originality/value

Few studies have examined the impact of integration on firms' capital structures in developing countries. After controlling for unobserved heterogeneity and endogeneity, this study adds new multilevel integration evidence on the capital structure of Chinese firms.
The impact of innovation aspiration shortfall and CEO origin on emerging economy firms' international expansion: evidence from China
Authors: Zhong Xi , Chen Weihong , Ren Ge
Published: June 2022

Purpose

Whether and when the innovation aspiration shortfall (e.g. innovation performance lower than aspirations) will affect emerging economy firms (EEFs)' international expansion remains an important unanswered theoretical and practical question.

Design/methodology/approach

Based on performance feedback theory, this study explores the impact of innovation aspiration shortfall on EEFs' international expansion and the moderating role of CEO origin.

Findings

This study finds that innovation aspiration shortfall has a positive impact on EEFs' international expansion. This study also uncovers that EEFs are less likely to implement international expansion in response to innovation aspiration shortfall when the CEO is a founder than when the CEO is a non-founder, and EEFs are more likely to implement international expansion in response to innovation aspiration shortfall when the CEO is an outsider-CEO than when the CEO is an insider-CEO.

Originality/value

This study proposes that the interaction between innovation aspiration shortfall and CEO origin can be a useful predictor of EEFs' international expansion.
Student-managed investment funds (SMIFs) in India: the perspectives of student fund managers
Authors: Joseph Alphil Maria , Jose Jerrin , Iyer Anusha Srinivasan
Published: June 2022

Purpose

This paper aims to explore how the student fund managers perceive the benefits of being part of the fund. Furthermore, this paper examines the country-specific challenges of setting up and managing a student-managed investment fund (SMIF) in India.

Design/methodology/approach

Qualitative content analysis technique is used to identify, compare and retrieve critical themes about the present state of SMIF clubs in India. The data collection method involved structured, in-depth online interviews with ten student fund managers from various higher educational institutions in India.

Findings

Some of the study’s key findings indicate that the existence of SMIFs as part of learning facilitates group decision-making and peer learning. Additionally, this study brings to light specific issues related to registration, incorporating real-world practices and integrating SMIF into the academic curriculum.

Social implications

The outcomes of this study shall be of use to students and the teaching fraternity across Indian colleges and universities who aspire to set up SMIFs as part of experiential learning. This study will also help existing SMIF clubs in India understand how their counterparts work and can consequently improvise their organizational structure and functioning.

Originality/value

To the best of the authors’ knowledge, this is the first interview-based evaluation of the present structure of SMIFs structured as clubs in India.
Proactive responses to job insecurity: why and when job-insecure employees engage in political behaviors
Authors: Zhang Junwei , Zhang Yajun , Lu Lu , Zhang Lei
Published: June 2022

Purpose

Drawing upon ego depletion theory, the authors developed a serial mediation model linking job insecurity with employee political behavior in which resource depletion and moral disengagement operated as two sequential mediators. The authors further identified employee moral identity as an important boundary condition that impacts the strength of this serial mediation effect.

Design/methodology/approach

Multilevel analyses were utilized to test the proposed hypotheses by analyzing a sample included 306 employees nested in 71 groups.

Findings

Results revealed that job insecurity induced resource depletion that activated moral disengagement, which in turn instigated political behavior. Furthermore, employee moral identity weakened this serial indirect effect. Specifically, this indirect effect was positive when moral identity was low, whereas did not present when moral identity was high.

Originality/value

Prior studies have primarily concentrated on the detrimental effects of job insecurity. However, less study has investigated how individuals proactively cope with job insecurity. The authors contribute to this stream of research by exploring whether and how job insecurity facilitates employee political behavior.