bluuebunny/crossref_metadata_2025 huggingface dataset:
Semantic overlap protects from interference by restoring encoding mechanisms
Authors: Moore Isabelle L. , Long Nicole M.
Published: February 2022

Overlap between experiences can have both facilitative and detrimental effects for memory. Our aim was to establish whether overlap along one dimension (e.g. contextual, semantic, temporal) can counteract overlap-driven interference along another dimension. We hypothesized that semantic overlap facilitates episodic memory formation by modulating encoding mechanisms. We recorded scalp electroencephalography (EEG) while human participants performed a free recall task. Half of the items from late in each study list semantically overlapped with an item presented earlier in the list. We find that semantic overlap selectively improves memory and influences the neural signals engaged during the study of late list items. Relative to other recalled items, late list items that are later recalled consecutively with semantically overlapping items elicited increased high frequency activity and decreased low frequency activity, a hallmark of successful encoding. Our findings demonstrate that semantic overlap can protect from interference due to temporal overlap by modulating encoding mechanisms.

Statement of Relevanc

Experiences can overlap along different dimensions, including contextual, semantic, and tempo-ral. We tested the hypothesis that semantic overlap – shared meaning between experiences – may protect from interference due to temporal overlap, when experiences occur close together in time. Although evidence suggests that attention and/or encoding resources diminish across a series of study items presented in close temporal proximity, we find that semantic overlap can enable recovery of these encoding resources. Specifically, items that would typically be forgotten due to interference are better remembered and recruit distinct neural mechanisms when they share meaning with an earlier study item. These findings indicate that encoding mechanisms can be modulated by the degree of semantic overlap between two experiences. More broadly, our results suggest that experiences do not exist in isolation, rather that a prior experience can directly influence the neural mechanisms recruited to process a current experience.
Post marketing surveillance for Microwave Treatment of Plantar and Common Warts in Adults
Authors: Bristow Ivan , Joshi Shailesh , Williamson Jonathan , Ardern-Jones Michael
Published: February 2022

A handheld microwave device (Swift®, Emblation Limited) has been licenced and available for clinical use since 2016 in the fields of podiatry and dermatology and has been extensively used in treating cutaneous warts. As part of post marketing surveillance by the manufacturer, an online 79-item survey was distributed to podiatry clinics in the United Kingdom with a Swift® device. A total of 126 clinics responded (59.6%). 6998 adults (<65 years) underwent wart treatment with microwave (81.9% plantar warts; 18.1% common, non-plantar warts). The median efficacy rate was reported as 79.2% (65.9 - 87.5%) and 82.3% (71.4 - 100%) respectively. In older adults (over 65 years) efficacy rates were similar for both sites: plantar (73.2%, 50-90%, n=1232) and non-plantar (80.0%, 42.1-100%, n=276). A median of three treatments was required to bring about resolution. Sub-group analysis of the data revealed good clearance rates in patients with diabetes (79.6%), but less in immunocompromised individuals (61.3%) and those with autoimmune disease (58.6%). Overall, mean user satisfaction was rated as “very satisfied” on a 10-point scale (n=93 practices). A small number of adverse events were reported including blistering, superficial ulceration and poor healing were reported (n=7). Despite the limitations of a post-marketing questionnaire survey, these data provide good evidence of the safety and efficacy for Swift® microwave treatment of cutaneous warts.

What is already known about this topic?

Microwave treatment has shown to be effective in the treatment of cutaneous warts.

What does the study add?

This survey of clinics using SWIFT microwave treatments reports on the effectiveness and safety of the device in the treatment of 8506 adult patients with common and plantar warts.

Responding user clinics reporting efficacy with good clearance rates and low levels of adverse events demonstrating microwave is a safe and effective treatment for plantar and common warts.
Algorithmic Identification of Potentially High Risk Abdominal Presentations (PHRAPs) to the Emergency Department: A Clinically-Oriented Machine Learning Approach
Authors: Kuzma Richard S , Saraswathula Varun , Moon Kathryn R , Kelz Rachel R , Friedman Ari B
Published: February 2022

Background

Older adults presenting to emergency departments (EDs) with abdominal pain have been shown to be at high risk of subsequent morbidity and mortality. Yet, such presentations are poorly studied in national databases. Claims databases do not record the patient’s symptoms at the time of presentation to the ED, but rather the diagnosis after testing and evaluation, limiting study of care and outcomes for these high risk abdominal presentations.

Objectives

We sought to develop an algorithm to define a patient population with potentially high risk abdominal presentations (PHRAPs) using only variables commonly available in claims data.

Research Design

Train a machine learning model to predict abdominal pain chief complaints using the National Hospital Ambulatory Medical Care Survey (NHAMCS), a nationally-representative database of abstracted ED medical records.

Subjects

All patients contained in NHAMCS data from 2013-2018. 2013-2017 were used for predictive modeling and 2018 was used as a hold-out test set.

Measures

Positive predictive value and sensitivity of the predictive algorithm against a hold-out test set of NHAMCS patients the algorithm was blinded to during training. Predictions were assessed for agreement with either a chief complaint of abdominal pain (contained in “Reason for Visit 1”), or an expanded definition intended to capture visits which were for abdominal concerns. These included secondary or tertiary complaints of abdominal pain or other abdominal conditions, other abdominal-related chief complaint (e.g. nausea or diarrhea, but not pain), discharge diagnosis of an abdominal condition, or reception of an abdominal CT or ultrasound.

Results

After validation on a hold-out data set, a gradient boosting machine (GBM) was the best best-performing machine learning model, but a logistic regression model had similar performance and may be more explainable and useful to future researchers. The GBM predicted a chief complaint of abdominal pain with a positive predictive value of 0.60 (95% CI of 0.56, 0.64) and a sensitivity of 0.29 (95% CI of (0.27, 0.32). Nearly all false positives still exhibited signs of “abdominal concerns” for patients: using the expanded definition of “abdominal concern” the model had a PPV of >0.99 (95% CI of 0.99, 1.00) and sensitivity of 0.12 (95% CI of 0.11, 0.13).

Conclusion

The algorithm we report defines a patient population with abdominal concerns for further study of treatment and outcomes to inform the development of clinical pathways.
Unique neural coding of crucial versus irrelevant plant odors in a hawkmoth
Authors: Bisch-Knaden Sonja , Rafter Michelle A. , Knaden Markus , Hansson Bill S.
Published: February 2022

The sense of smell is pivotal for nocturnal moths to locate feeding and oviposition sites. However, these crucial resources are often rare and their bouquets are intermingled with volatiles emanating from surrounding ‘background’ plants. Here we asked if the olfactory system of female hawkmoths, Manduca sexta, could differentiate between crucial and background cues. To answer this question, we collected nocturnal headspaces of numerous plants in a natural habitat of M. sexta. We analyzed the chemical composition of these headspaces, and used them as stimuli in physiological experiments at the antenna and in the brain. The intense odors of floral nectar sources evoked strong responses in virgin and mated female moths, most likely enabling the localization of profitable flowers at a distance. Bouquets of larval host plants and most background plants, in contrast, were subtle, thus potentially complicating host identification. However, despite being subtle, antennal responses and brain activation patterns evoked by the smell of larval host plants were clearly different from those evoked by other plants. Interestingly, this difference was even more pronounced in the antennal lobe of mated females, revealing a status-dependent tuning of their olfactory system towards oviposition sites. Our study suggests that female moths possess unique neural coding strategies to find not only conspicuous floral cues but also inconspicuous bouquets of larval host plants within a complex olfactory landscape.
FoxP3 can fold into two distinct dimerization states with divergent functional implications for T cell homeostasis
Authors: Leng Fangwei , Zhang Wenxiang , Ramirez Ricardo N. , Leon Juliette , Zhong Yi , van der Veeken Joris , Rudensky Alexander Y. , Benoist Christophe , Hur Sun
Published: February 2022

FoxP3 is an essential transcription factor (TF) for immunologic homeostasis, but how it utilizes the common forkhead DNA-binding domain (DBD) to perform its unique function remains poorly understood. We here demonstrate that, unlike other known forkhead TFs, FoxP3 forms a head-to-head dimer using a unique linker (Runx1-binding region, RBR) preceding the forkhead domain. Head-to-head dimerization confers distinct DNA-binding specificity and creates a docking site for the cofactor Runx1. RBR is also important for proper folding of the forkhead domain, as truncation of RBR induces domain-swap dimerization of forkhead, which was previously considered the physiological form of FoxP3. Rather, swap-dimerization impairs FoxP3 function, as demonstrated with the disease-causing mutation R337Q, while a swap-suppressive mutation largely rescues R337Q-mediated functional impairment. Altogether, our findings suggest that FoxP3 can fold into two distinct dimerization states: head-to-head dimerization representing functional specialization of an ancient DBD and swap-dimerization with impaired functions.
Recombination-aware Phylogeographic Inference Using the Structured Coalescent with Ancestral Recombination
Authors: Guo Fangfang , Carbone Ignazio , Rasmussen David A.
Published: February 2022

Movement of individuals between populations or demes is often restricted, especially between geographically isolated populations. The structured coalescent provides an elegant theoretical framework for describing how movement between populations shapes the genealogical history of sampled individuals and thereby structures genetic variation within and between populations. However, in the presence of recombination an individual may inherit different regions of their genome from different parents, resulting in a mosaic of genealogical histories across the genome, which can be represented by an Ancestral Recombination Graph (ARG). In this case, different genomic regions may have different ancestral histories and so different histories of movement between populations. Recombination therefore poses an additional challenge to phylogeographic methods that aim to reconstruct the movement of individuals from genealogies, although also a potential benefit in that different loci may contain additional information about movement. Here, we introduce the Structured Coalescent with Ancestral Recombination (SCAR) model, which builds on recent approximations to the structured coalescent by incorporating recombination into the ancestry of sampled individuals. The SCAR model allows us to infer how the migration history of sampled individuals varies across the genome from ARGs, and improves estimation of key population genetic parameters such as population sizes, recombination rates and migration rates. Using the SCAR model, we explore the potential and limitations of phylogeographic inference using full ARGs. We then apply the SCAR to lineages of the recombining fungusAspergillus flavussampled across the United States to explore patterns of recombination and migration across the genome.
Removal Of Environmental Pollutants (Lead, Chromium And Cadmium) Using Root And Leaf Tissues Of Indian Mustard, Rice And Wheat Plants
Authors: Halder Shema , Anirban Apurba
Published: February 2022

The environment is polluted day by day and it is very much expensive to remediate the environmental pollutants by physicochemical process. Therefore, using plants as a process to remediate pollutants is essential. In this study, phytoremediation of root and leaf tissues of Indian mustard (Brassica juncea), rice (Oryza sativa) and wheat (Triticum aestivum) against three most environment pollutants viz. lead (Pb), chromium (Cr) and cadmium (Cd) of Buriganga riverbank soil of Dhaka city, Bangladesh were assessed. The highest amount of Pb was found in the leaf (11.6755 ±1.9860 mg/kg dry weight) and root (51.4251 ±5.0320 mg/kg dry weight) of B. juncea. However, the highest amount of Cr was found in the leaf (5.9871±0.9032 mg/kg dry weight) of B. juncea; and in the root (46.4739±2.2920 mg/kg dry weight) of O. sativa respectively. Although the highest amount (0.9624±0.0920 mg/kg dry weight) of Cd was found in the leaf of B. juncea; the amount of Cd in the root was approximately same in all the three plants. This research also found more amounts of heavy metals compared to other studies using Indian mustard, rice and wheat against the three most environmental pollutants viz., Pb, Cr and Cd. Moreover, this study revealed that B. juncea is the highest hyperaccumulator species regarding Pb, Cr and Cd accumulation and can be used to clean up the polluted Buriganga riverbank soil.
Associations between antipsychotic use, substance use and relapse risks in patients with schizophrenia - real-world evidence from two national cohorts
Authors: Lähteenvuo Markku , Luykx Jurjen J. , Taipale Heidi , Mittendorfer-Rutz Ellenor , Tanskanen Antti , Batalla Albert , Tiihonen Jari
Published: February 2022

Background

Research on the effectiveness of pharmacotherapies for schizophrenia-substance use disorder comorbidity (Sch-SUD) is very sparse and non-existent on the prevention of the development of substance use disorders (SUD) in patients with schizophrenia.

Aims

To compare the real-world effectiveness of antipsychotics in schizophrenia in decreasing risks of: 1) development of an initial SUD; and 2) psychiatric hospitalization and hospitalization due to SUD among patients with SUD.

Methods

Two independent national cohorts including all persons diagnosed with schizophrenia (N=45,476) were followed up for 22 (Finland: 1996–2017) and 11 years (Sweden: 2006–2016). Risks of developing SUD were calculated with between-individual models, and risks of psychiatric and SUD hospitalization with within-individual models using Cox regression and adjusted Hazard Ratios (aHRs) when using vs. not using certain antipsychotics.

Results

For schizophrenia patients without SUDs, clozapine use (aHR 0.20, 95%CI 0.16–0.24, p<0.001, in Finland; 0.35, 0.24–0.50, p<0.001, in Sweden) was associated with lowest risks of developing an initial SUD in both countries. Antipsychotic polytherapy was associated with second lowest risk (0.54, 0.44-0.66) in Sweden, and third lowest risk (0.47, 0.42-0.53) in Finland. Risks of psychiatric hospitalization and hospitalization due to SUD were lowest during use of clozapine, antipsychotic polytherapy, and long-acting injectables in both countries. Results were consistent across both countries.

Conclusion

Clozapine and antipsychotic polytherapy are most strongly associated with reduced chances of developing SUDs among patients with schizophrenia and with lower relapse rates among patients with both diagnoses.
Use of digital technology tools to characterize patient adherence to prescription-grade omega-3 polyunsaturated fatty acid therapy: Primary results of the DIAPAsOn prospective observational study
Authors: Arutyunov Gregory P. , Arutyunov Alexander G. , Ageev Fail T. , Fofanova Tatiana V.
Published: February 2022

Background, objectives and methods

DIAPAsOn was a 6-month prospective observational multicenter study in the Russian Federation that examined adherence to a preparation of highly purified omega-3 polyunsaturated fatty acids (OMACOR) in adult patients with a history of recent myocardial infarction or endogenous hypertriglyceridemia. A full description of the study’s aims and methods has appeared in JMIR Res Protoc. A feature of DIAPAsOn was the use of a bespoke electronic patient engagement and data collection system.

Results

The net average reduction from baseline in both total and low-density lipoprotein cholesterol was approximately 1 mmol/L and the net average increment in high-density lipoprotein cholesterol was 0.2±0.53 mmol/L. Mean triglyceride levels declined by ∼1.3 mmol/, from an initial level of 2.99±1.29 mmol/L to 1.67± 0.67 mmol/L. The percentage of patients with triglyceride <1.7 mmol/L rose from 13.1% at baseline to 54% at study-end.

Digital reporting of adherence was registered by 8.3% of patients (n=180) and average scores indicted poor adherence. However, clinic-based enquiry suggested high levels of adherence.

Data on health-related quality of life accrued from digitally-engaged patients identified improvements among patients reporting high adherence to study treatment, but patient numbers were small.

Conclusions

The lipid and lipoprotein findings indicate that OMACOR had nominally favorable effects on the blood lipid profile. Less than 10% of patients enrolled in DIAPAsOn used the bespoke digital platform piloted in the study and the level of self-reported adherence to medication by those patients was also low. Reasons for this low uptake and adherence are unclear. Better adherence was recorded by clinical report.
Factors associated with contraceptive failure in Uganda: Analysis of the 2016 Uganda Demographic and Health Survey
Authors: Kisuza Ruth Ketty , Kicaber Saviour , Bary Derrick Abila , Bongomin Felix , Garimoi Christopher Orach
Published: February 2022

Introduction

Sustained motivation is essential for effective use of contraceptive methods by women in low- and middle-income countries as many women are likely to abandon use of contraceptives especially when they continually experience episodes of failure. We aimed to determine contraceptive failure rates and associated factors among Ugandan women using data from the 2016 Uganda Demographic Health Survey (UDHS).

Methods

We analyzed data collected by the UDHS conducted in Uganda 2016. All eligible women aged 15 to 49 years at the time of the survey were enrolled. Discontinuation of contraceptive use due to failure within a 5-year period preceding the survey was the dependent variable.

Results

A total of 18,505 women were included in this study, 70.8% (n=5153) lived in rural areas while 56.9% (n=5153) owned a mobile phone. The mean age of the women was 29.6years (SD 7.6). The overall prevalence of contraceptive failure was 5.6%, and was higher (7.8%) among women aged 25-29 years or had completed secondary education (7.1%). The odds of contraceptive failure was 38% lower in women who had an informed choice on contraceptives compared to those who didn’t [Adjusted Odd ratio, 0.62; 95% confidence interval, 0.50 – 0.77; p< 0.001].

Conclusion

The burden of contraceptive failure among women of reproductive age in Uganda is substantial and significantly varied by socio-demographic characteristics.
Differential antibody production by symptomatology in SARS-CoV-2 convalescent individuals
Authors: Saraf Sharada , Zhu Xianming , Shrestha Ruchee , Bonny Tania S. , Baker Owen R. , Beck Evan J. , Fernandez Reinaldo E. , Eby Yolanda , Akinde Olivia , Ruff Jessica E. , Caturegli Patrizio , Redd Andrew D. , Bloch Evan M. , Quinn Thomas C. , Tobian Aaron AR , Laeyendecker Oliver
Published: February 2022

The association between COVID-19 symptoms and antibody responses against SARS-CoV-2 is poorly characterized. We analyzed antibody levels in individuals with known SARS-CoV-2 infection to identify potential antibody-symptom associations. Convalescent plasma from 216 SARS-CoV-2 RNA+ individuals with symptomatology information were tested for the presence of IgG to the spike S1 subunit (Euroimmun ELISA), IgG to receptor binding domain (RBD, CoronaCHEK rapid test), and for IgG, IgA, and IgM to nucleocapsid (N, Bio-Rad ELISA). Logistic regression was used to estimate the odds of having a COVID-19 symptom from the antibody response, adjusting for sex and age. Cough strongly associated with antibodies against S1 (adjusted odds ratio [aOR]= 5.33; 95% CI from 1.51 to 18.86) and RBD (aOR=4.36; CI 1.49, 12.78). In contrast, sore throat significantly associated with the absence of antibodies to S1 and N (aOR=0.25; CI 0.08, 0.80 and aOR=0.31; 0.11, 0.91). Similarly, lack of symptoms associated with the absence of antibodies to N and RBD (aOR=0.16; CI 0.03, 0.97 and aOR=0.16; CI 0.03, 1.01). Cough appeared to be correlated with a seropositive result, suggesting that SARS-CoV-2 infected individuals exhibiting lower respiratory symptoms generate a robust antibody response. Conversely, those without symptoms or limited to a sore throat while infected with SARS-CoV-2 were likely to lack a detectable antibody response. These findings strongly support the notion that severity of infection correlates with robust antibody response.
Association between Liver Fibrosis and Incident Dementia in the UK Biobank Study
Authors: Parikh Neal S. , Kamel Hooman , Zhang Cenai , Kumar Sonal , Rosenblatt Russell , Spincemaille Pascal , Gupta Ajay , Cohen David E. , de Leon Mony J. , Gottesman Rebecca F. , Iadecola Costantino
Published: February 2022

Background

There is growing recognition of the role of chronic liver disease in brain health, but the impact of liver fibrosis on dementia risk was unclear. We evaluated the association between liver fibrosis and incident dementia using data from a large prospective cohort study.

Methods

We performed a cohort analysis using data from the UK Biobank study, which prospectively enrolled approximately 500,000 adults starting 2007 and continues to follow them. Liver fibrosis was defined using validated cutoffs of the Fibrosis-4 (FIB-4) liver fibrosis score. The primary outcome was incident dementia, ascertained using a validated approach based on participants’ hospital record and mortality data. Secondary outcomes were Alzheimer’s disease and vascular dementia. We excluded participants with prevalent dementia. We used Cox proportional hazards models to evaluate the association between liver fibrosis and incident dementia while adjusting for potential confounders. In additional models, the FIB-4 score was used as a continuous independent variable. Prespecified interaction analyses tested for effect modification by sex, metabolic syndrome, and apolipoprotein E4 carrier status.

Results

Among 455,226 participants included in this analysis, the mean age was 56.5 years and 54% were women. Standard liver chemistries were largely in the normal range. However, 2.17% (95% CI, 2.13-2.22%) had liver fibrosis based on their FIB-4 score. The rate of dementia per 1,000 person-years was 1.76 (95% CI, 1.50-2.07) in participants with liver fibrosis and 0.52 (95% CI, 0.50-0.54) in those without. After adjusting for demographics, socioeconomic deprivation, educational attainment, metabolic syndrome, hypertension, diabetes, dyslipidemia, and tobacco and alcohol use, liver fibrosis was associated with an increased risk of dementia (HR, 1.52; 95% CI, 1.22-1.90). An independent association was also noted between FIB-4, treated as a continuous variable, and dementia (HR per unit, 1.29; 95% CI, 1.20-1.39). Effect modification by sex, metabolic syndrome, and apolipoprotein E4 carrier status was not seen.

Conclusion

Liver fibrosis in middle age was associated with an increased risk of incident dementia, independent of metabolic syndrome and shared risk factors. Liver fibrosis may be an underrecognized risk factor for dementia.
Sensitive Spatiotemporal Tracking of Spontaneous Metastasis in Deep Tissues via a Genetically-Encoded Magnetic Resonance Imaging Reporter
Authors: Nyström Nivin N. , McRae Sean W. , Martinez Francisco F.M. , Kelly John J. , Scholl Timothy J. , Ronald John A.
Published: February 2022

Metastasis remains a poorly understood aspect of cancer biology and the leading cause of cancer-related death, yet most preclinical cancer studies do not examine metastasis, focusing solely on the primary tumor. One major factor contributing to this paradox is a gap in available tools for accurate spatiotemporal measurements of metastatic spread in vivo. Our objective was to develop an imaging reporter system that offers sensitive three-dimensional detection of cancer cells at high resolutions in live mice. We utilized organic anion-transporting polypeptide lb3 (oatp1b3) as a magnetic resonance imaging (MRI) reporter gene to this end, and systematically optimized its framework for in vivo tracking of viable cancer cells in a spontaneous metastasis model. We were able to image metastasis on oatp1b3-MRI at the single lymph node level and continued to track its progression over time as cancer cells spread to multiple lymph nodes and different organ systems in single animals. While initial single lesions were successfully imaged in parallel via bioluminescence, later metastases were obscured by light scatter from the initial node. Importantly, we demonstrate and validate that 100-μm isotropic resolution MR images could detect micrometastases in lung tissue estimated to contain fewer than 103 cancer cells. In summary, oatp1b3-MRI enables precise determination of lesion size and location over time and offers a path towards deep-tissue tracking of any oatp1b3-engineered cell type with combined high resolution, high sensitivity, 3D spatial information, and surrounding anatomical context.
Transgenic microalgae expressing double-stranded RNA as potential feed supplements for controlling white spot syndrome in shrimp aquaculture
Authors: Charoonnart Patai , Taunt Henry N , Yang Luyao , Webb Conner , Purton Saul , Robinson Colin , Saksmerprome Vanvimon
Published: February 2022

Viral infection of farmed fish and shellfish represents a major issue within the aquaculture industry. One potential control strategy involves RNA interference of viral gene expression through the oral delivery of specific double-stranded RNA (dsRNA). In previous work we have shown that recombinant dsRNA can be produced in the chloroplast of the edible microalga,Chlamydomonas reinhardtiiand used to control disease in shrimp. Here we report a significant improvement in antiviral dsRNA production and its use to protect shrimp against white spot syndrome virus (WSSV). A new strategy for dsRNA synthesis was developed that uses two convergent copies of the endogenousrrnSpromoter to drive high level transcription of both strands of the WSSV gene element in the chloroplast. New vectors were designed that allow rapid Golden Gate-mediated assembly of a transformation plasmid in which the ‘dual promoter-WSSV DNA’ cassette is targeted into the chloroplast genome, with selection based on the restoration of photosynthesis. PCR analysis of transformant lines confirmed the integration of the cassette and homoplasmy of the polyploid genome. Transcribed sense and antisense VP28-RNA were hypothesised to form an RNA duplex in the chloroplast stroma, and quantitative RT-PCR indicated that ∼100 μg dsRNA is produced per litre of transgenic microalgae culture. This represents an ∼10,000-fold increase in dsRNA relative to previous reports using convergentpsaApromoters. The engineered alga was assessed for its ability to prevent WSSV infection when fed to shrimp larvae prior to a challenge with the virus. Survival of shrimp fed with dsRNA-expressingC. reinhardtiiwas significantly enhanced (68.3%) relative to the negative control. The study suggests that this new dsRNA production platform is significantly more efficient than that reported previously, and merits further scale-up and downstream processing studies.
Developmental overproduction of cortical superficial neurons impairs adult auditory cortical processing
Authors: Merkler Mirna , Ip Nancy Y , Sakata Shuzo
Published: February 2022

While evolutionary cortical expansion is thought to underlie the evolution of human cognitive capabilities, excessive developmental expansion can lead to megalencephaly, often found in neurodevelopmental disorders such as autism spectrum disorder. Still, little is known about how the overproduction of cortical neurons during development affects cortical processing and behavior in later life. Here we show that the developmental overproduction of cortical superficial neurons impairs auditory processing in mice. We took advantage of a WNT/β- catenin signaling inhibitor, XAV939, to overproduce cortical superficial excitatory neurons during development. XAV939-treated adult mice exhibited a longer reaction time and a higher threshold to detect acoustic stimuli behaviorally. This mouse model also demonstrated abnormal auditory cortical processing depending on experimental conditions: in a passive listening condition, we observed lower beta power and lower spontaneous and auditory-evoked activity in putative excitatory cells whereas higher pre-stimulus spontaneous activity in excitatory cells is associated with failing to detect auditory stimuli behaviorally. On the other hand, the auditory thalamus did not show any significant difference in neural firing between XAV939-treated and control groups. Furthermore, functional monosynaptic connections were significantly reduced between cortical putative excitatory cells. Altogether, our results suggest that the atypical auditory detectability of XAV939-treated animals can be explained by abnormal auditory cortical processing. Although the expansion of cortical size is evolutionarily advantageous, an abnormal expansion during development can result in detrimental effects on cortical processing and perceptual behavior in adulthood.
Single-cell multi-region dissection of brain vasculature in Alzheimer’s Disease
Authors: Sun Na , Akay Leyla Anne , Murdock Mitchell H. , Park Yongjin , Bubnys Adele , Galani Kyriaki , Mathys Hansruedi , Jiang Xueqiao , Ng Ayesha P. , Bennett David A. , Tsai Li-Huei , Kellis Manolis
Published: February 2022

Cerebrovascular breakdown occurs early in Alzheimer’s Disease (AD), but its cell-type-specific molecular basis remains uncharacterized. Here, we characterize single-cell transcriptomic differences in human cerebrovasculature across 220 AD and 208 control individuals and across 6 brain regions. We annotate 22,514 cerebrovascular cells in 11 subtypes of endothelial, pericyte, smooth muscle, perivascular fibroblast, and ependymal cells, and how they differ in abundance and gene expression between brain regions. We identify 2,676 AD-differential genes, including lower expression of PDGFRB in pericytes, and ABCB1 and ATP10A in endothelial cells. These AD-differential genes reveal common upstream regulators, including MECOM, EP300, and KLF4, whose targeting may help restore vasculature function. We find coordinated vasculature-glial-neuronal co-expressed gene modules supported by ligand-receptor pairs, involved in axon growth/degeneration and neurogenesis, suggesting mechanistic mediators of neurovascular unit dysregulation in AD. Integration with AD genetics reveals 125 AD-differential genes directly linked to AD-associated genetic variants (through vasculature-specific eQTLs, Hi-C, and correlation-based evidence), 559 targeted by AD-associated regulators, and 661 targeted by AD-associated ligand-receptor signaling. Lastly, we show that APOE4-genotype associated differences are significantly enriched among AD-associated genes in capillary and venule endothelial cells, and subsets of pericytes and fibroblasts, which underlie the vascular dysregulation in APOE4-associated cognitive decline. Overall, our multi-region molecular atlas of differential human cerebrovasculature genes and pathways in AD can help guide early-stage AD therapeutics.
Rapid evaporative ionisation mass spectrometry (REIMS): A potential and rapid tool for the identification of insecticide resistance in mosquito larvae
Authors: Morgan Jasmine , Salcedo-Sora J. Enrique , Wagner Iris , Beynon Robert J , Triana-Chavez Omar , Strode Clare
Published: February 2022

Insecticide resistance is a significant challenge facing the successful control of mosquito vectors globally. Bioassays are currently the only method for phenotyping resistance. They require large numbers of mosquitoes for testing, the availability of a susceptible comparator strain and often insectary facilities. This study aimed to trial the novel use of rapid evaporative ionisation mass spectrometry (REIMS) for the identification of insecticide resistance in mosquitoes. No sample preparation is required for REIMS and analysis can be rapidly conducted within hours. Temephos resistant Aedes aegypti (Linnaeus) larvae from Cúcuta, Colombia and temephos susceptible larvae from two origins (Bello, Colombia, and the lab reference strain New Orleans) were analysed using REIMS. We tested the ability of REIMS to differentiate three relevant variants: population source, lab versus field origin and response to insecticide. The classification of these data was undertaken using linear discriminant analysis (LDA) and random forest. Classification models built using REIMS data were able to differentiate between Ae. aegypti larvae from different populations with 82% (± 0.01) accuracy, between mosquitoes of field and lab origin with 89% (± 0.01) accuracy and between susceptible and resistant larvae with 85% (± 0.01) accuracy. LDA classifiers had higher efficiency than random forest with this data set. The high accuracy observed here identifies REIMS as a potential new tool for rapid identification of resistance in mosquitoes. We argue that REIMS and similar modern phenotyping alternatives should complement existing insecticide resistance management tools.
State-dependent activity dynamics of hypothalamic stress effector neurons
Authors: Ichiyama Aoi , Mestern Samuel , Benigno Gabriel B. , Scott Kaela E. , Allman Brian L. , Muller Lyle , Inoue Wataru
Published: February 2022

The stress response necessitates an immediate boost in vital physiological functions from their homeostatic operation to elevated emergency response. However, neural mechanisms underlying this state-dependent change remain largely unknown. Using a combination of in vivo and ex vivo electrophysiology with computational modeling, we report that corticotropin releasing hormone (CRH) neurons in the paraventricular nucleus of the hypothalamus (PVN), the effector neurons of hormonal stress response, rapidly transition between distinct activity states through recurrent inhibition. Specifically, in vivo optrode recording shows that under non-stress conditions, CRHPVN neurons often fire with rhythmic brief bursts (RB), which, somewhat counterintuitively, constrains firing rate due to long (∼2 s) inter-burst intervals. Stressful stimuli rapidly switch RB to continuous single spiking (SS), permitting a large increase in firing rate. A spiking network model shows that recurrent inhibition can control this activity-state switch, and more broadly the gain of spiking responses to excitatory inputs. In biological CRHPVN neurons ex vivo, the injection of whole-cell currents derived from our computational model recreates the in vivo-like switch between RB and SS, providing a direct evidence that physiologically relevant network inputs enable state-dependent computation in single neurons. Together, we present a novel mechanism for state-dependent activity dynamics in CRHPVN neurons.
Distorted zinc coordination polyhedra in bis(1-ethoxy-2-{[(2-methoxyethyl)imino]methyl}propan-1-olato)zinc, a possible CVD precursor for zinc oxide thin films
Authors: Johnson Keneshia O. , Brown Antionette , Farris Gabriella , Starks Alexabria , Butcher Ray J. , Matthews Jason S.
Published: February 2022

A new metal–organic precursor for the chemical vapor deposition of zinc oxide thin films, [Zn(C9H16NO3)2], has been synthesized and characterized by 1H and 13C NMR spectroscopy, single-crystal X-ray diffraction and thermogravimetric analysis. The asymmetric unit of the title compound consists of two molecules (Z′ = 2), with different zinc coordination polyhedra. In one molecule, the metal atom is in a distorted trigonal–bipyramidal ZnN2O3 environment (τ5 = 0.192) with a long bond to an ether O donor atom [Zn—O = 2.727 (6) Å]. In the other, the Zn atom is in a distorted ZnN2O4 octahedral environment with long bonds to the ether O donors of both ligands [Zn—O = 2.514 (4) and 2.661 (4) Å; O—Zn—O = 82.46 (14)°]. The crystal structure features weak C—H...·O interactions.
Does deterrence-based enforcement matter in alms tax (Zakat) compliance?
Authors: Abdul-Jabbar Hijattulah , Bin-Nashwan Saeed Awadh
Published: February 2022

Purpose

Government seeks to realize its economic objectives and eventually its social objectives as well through taxation. In a Muslim-majority economy, besides many types of taxation imposed, some government also legally enforced an alms tax (Zakat) via specific authority. The purpose of this study is to examine the role of enforcement in Zakat compliance and how it can enhance the effect of social motivations, namely perceived institutional credibility and social pressure, on zakat payers' compliance decisions.

Design/methodology/approach

This research is underpinned by economic deterrence theory and employed data collected through a cross-sectional approach. A total of 274 Yemeni entrepreneurs responded to the questionnaire and analysed using SmartPLS version 3.2.9.

Findings

The study finds that social pressure and institutional credibility are significantly related to entrepreneurs' compliance with Zakat. Importantly, enforcement-moderated interactions of social pressure and perceived credibility on Zakat payers' compliance are statistically significant.

Practical implications

Some signals emerged from the results which could be used by governments throughout the Muslim-majority state to mitigate Zakat evasion amongst entrepreneurs. Furthermore, the study can provide information to Zakat authorities and policymakers on how to restore public trustworthiness and increase Zakat collection from entrepreneurs as well as cautioning such authorities that social pressure may possess an unfavourable attitude towards Zakat laws, influencing Zakat payers to do this action itself.

Originality/value

This study provides a shred of unique evidence by suggesting a new approach to the Zakat literature and linking the deterrence-based enforcement and social motivation with practice, which contributes to strengthening compliance levels amongst entrepreneurs and ultimately enhancing Zakat funds.
Sustainability and entrepreneurship: emerging opportunities for business and management education
Authors: Ortiz-de-Urbina-Criado Marta , Mora-Valentín Eva-María , Nájera-Sánchez Juan-José
Published: February 2022

Purpose

Agenda 2030 for Sustainable Development defines 17 goals with 169 targets in economic, social and environmental fields to guarantee human rights. Universities and companies are two driving forces for achieving these Sustainable Development Goals (SDGs). In this context, university research and, specifically, business and management studies should include this new economic-social panorama. Focusing on business and management education, this study aims to analyze who can help to implement the SDGs and how.

Design/methodology/approach

A descriptive examination of the evolution of documents and journals on business and management education was performed. Next, a co-authorship analysis, studying the collaboration among researchers, was performed. Finally, a co-word analysis that identifies the main topics and relationships between them was developed.

Findings

This study’s results suggest the necessity of expanding collaboration networks between countries and institutions. The analysis also reveals two emergent topics: entrepreneurship and sustainability. Then, three lines for teaching business and management according to the SDGs are proposed: two regarding university-firm relationships – job creation and entrepreneurship – and the third regarding universities effects on society – including sustainability principles and actions in higher education.

Originality/value

The main contribution is to show the important role that universities, in general, and business and management education, in particular, play in achieving the SDGs. Universities must mobilize their managers, professors and students because implementing the SDGs is possible through coordinated and integrated participation.
Socio-technological framework for selecting suppliers of pharmaceuticals in a pandemic environment
Authors: Chauhan Ankur , Jakhar Suresh Kumar , Kumar Mangla Sachin
Published: February 2022

Purpose

During pre-vaccine era, pharmaceutical supplies [self-care essentials (SCEs)] have been proved to be a major deflector, protector and safety guard against novel coronavirus disease (COVID-19). Hence, the objective of the study is to provide a comprehensive socio-technological decision-making framework based on multiple criteria for selecting the suppliers of pharmaceuticals, such as SCEs, by multi-brand enterprises (distributors) in the pandemic environment.

Design/methodology/approach

A hybrid methodology of Bayesian best worst method (BWM) and multi-attributive border approximation area comparison (MABAC) method has been applied for carrying out the study. Bayesian BWM has been applied for computing the importance of criteria identified for the selection of SCEs' suppliers during pandemic environment and MABAC method evaluated the suppliers of the SCEs.

Findings

In the study, the authors have identified eight criteria such as disinfection and sanitization of vehicles, social conscience of suppliers, brand (Technological recognition) of SCEs and logistics and distribution network, among others, which are critical to the selection of a supplier for the supply of SCEs. The application of the proposed hybrid model revealed that lead time and quality of SCEs are of utmost concern for pharmacies in a pandemic environment. Among the ten suppliers, results showed that Suppliers 2, 4 and 5 have been ranked first for supplying hand wash, hand sanitizer and face mask, respectively.

Practical implications

The proposed model has helped the multi-brand distributors of pharmaceuticals in selecting suppliers during the ongoing crisis of COVID-19. In addition to that, in future the outcomes of the study would be helpful for multi-brand distributors as well as pharmacies and hospitals in selecting the best suppliers. Policy makers will be able to make and revise the policies immediately with the help of the proposed decision-making framework.

Originality/value

The paper makes a novel contribution towards theory with the criteria identified for selecting best suppliers during the pandemic COVID-19. Additionally, the proposed hybrid model helps multi-brand distributors of pharmaceuticals in making decisions that lead to a huge social and economic success in pandemic time.
Plea bargain dilemma, financial crime and asset recovery
Authors: Korejo Muhammad Saleem , Rajamanickam Ramalinggam , Md. Said Muhamad Helmi , Korejo Erum Naseer
Published: February 2022

Purpose

This paper aims to debate moral and legal dilemma embedded with plea bargaining (PB) and raises a question whether the approach of “PB” is a viable tool to tackle financial crimes and to what extent it contributes in recovery of stolen money. This paper critically examines the concept with reference to relevant laws of the USA, the UK, Pakistan and Nigeria.

Design/methodology/approach

This study used legal scholarship, jurisprudence and other open source data to analyze issues in the application of PB as a viable tool in asset recovery and financial crimes.

Findings

This paper provides that PB has certain moral and legal dilemma in terms of legality and punishment; the concept offers a sense of escape from criminal punishment by simply return of partial stolen money or “settlement” in exchange of discounted punishment even without imprisonment, thus incentivizing an offender. Further, the concept is unregulated, misapplied especially in developing world like Pakistan and Nigeria, where plea bargain laws are mostly manipulated by white-collar individuals. Therefore, this study recommends the amendment of relevant laws pertaining to PB; construction of “plea bargain handbook” to prevent arbitrariness and misapplication and to ensure transparency in its application; legislations like Speedy Trail Act; creation of “Fast Track-Model Courts” and a balancing system between “settlement” and “deterrence.”

Originality/value

Perspectives on PB are brought to bear from financial crime and malpractice and recovery of stolen money.
Improving theory use in social marketing: the TITE four-step theory application process
Authors: Willmott Taylor Jade , Rundle-Thiele Sharyn
Published: February 2022

Purpose

Theory remains underused in social marketing despite many potential benefits that may arise if theory is concretely and consistently applied. In response to ongoing calls for standardised frameworks and methods, this study aims to present a four-step theory application process with the aim of supporting improved theory use across the entire social marketing process.

Design/methodology/approach

The role and importance of theory application in behaviour change is outlined alongside an integrative review and critical analysis of theory application in social marketing. To address key challenges impeding rigorous theory use, the theory selection, iterative schematisation, theory testing and explicit reporting of theory use (TITE) four-step theory application process is proposed. Evidence-based guidance, current best practice examples, and a worked example are provided to illustrate how the TITE process may be initially followed.

Findings

Low levels and poor quality of theory use suggest social marketing researchers and practitioners need further support in rigorously applying theories across the life of an intervention. The TITE process leverages the known benefits of theory use and capitalises on the reciprocal relationship that may be enacted between theory selection, iterative schematisation, theory testing and explicit reporting of theory use.

Research limitations/implications

The TITE process delivers a standardised framework that aims to stimulate rigorous theory application and explicit reporting of theory use in social marketing. Clear theory application and reporting will permit a more fine-grained understanding of intervention effectiveness to be established by shifting away from a simple dichotomous view of effectiveness (success or failure) to unpacking the “active ingredients” contributing to observed outcomes.

Practical implications

The evidence-based guidance and best practice examples provided for each step of the TITE process will increase the accessibility and usability of theory among practitioners. With time the TITE process will support practitioners by delivering a robust theory base that can be reliably followed to further extend on social marketing’s effectiveness.

Originality/value

This paper draws on interdisciplinary methods and resources to propose a standardised framework – the TITE process – designed to support rigorous theory application and explicit reporting of theory use in social marketing. Refinement, uptake and widespread implementation of the TITE process will improve theory use and support the creation of a shared language, thereby advancing social marketing’s cumulative knowledge base over time.