bluuebunny/crossref_metadata_2025 huggingface dataset:
Concerns from Community Mental Health Center (CMHC) Patients Regarding Drug-Induced Movement Disorders: Impact on Functioning and Treatment Beliefs
Authors: Stiles Allison , Franey Ericha , Goldberg Edward , Lundt Leslie , Yonan Chuck , Dhanda Rahul
Published: May 2021

Objective

Drug-induced movement disorders (DIMDs) may occur in patients treated with antipsychotics. The CommonGround Program supports the recovery and healing of psychiatric outpatients through tools which facilitate better patient-doctor communication regarding psychiatric symptoms, DIMDs, and the effectiveness of treatment.

Methods

Patients responses to CommonGround’s web-based waiting-room questionnaire were analyzed in patients who responded yes to having concerns about developing DIMDs (MD-YES) and those who responded no to this question (MD-NO). These groups were compared descriptively to assess the potential effects of DIMD concerns on self-reported functioning and beliefs about prescribed psychiatric medications.

Results

Of 7874 responding patients, 312 (4.0%) and 7562 (96.0%) were in the MD-YES and MD-NO subgroups, respectively. A higher percentage of MD-YES patients reported poor / not so good ability to keep up with daily responsibilities (21.2% vs 15.2% vs MD-NO), along with low energy levels (37.1% vs 26.3% for MD-NO), bothersome thoughts/beliefs/fears (30.5% vs 16.0%), and nervousness/anxiety (35.3% vs 27.5%) all / most of the time. MD-YES patients were also more likely to wonder about stopping their medications (9.3% vs 0.6% for MD-NO) and were concerned about side effects such as sleepiness (31.4% vs 3.9%) and weight gain (37.2% vs 5.7%).

Conclusion

Patients from community mental health centers who were concerned about developing DIMDs tended to express problems with daily functioning and concerns about their psychiatric medications. For these patients, recognizing their fears and concerns may help clinicians discuss treatment options for DIMDs, which could increase patient confidence, encourage adherence to current psychiatric medications, and potentially improve outcomes.
Knowledge of The Recognition and Management of Tardive Dyskinesia Markedly Improved Among Psychiatrists: Assessing the Impact of Online Medical Education
Authors: Finnegan Thomas , Mehra Anjali , Lubarda Jovana , Shah Chirag , Cutler Andrew J.
Published: May 2021

Introduction

Tardive dyskinesia (TD) is a persistent and potentially disabling movement disorder associated with prolonged exposure to antipsychotic medications that jeopardizes adherence to treatment and reduces quality of life. The recognition and management of TD can be challenging in many instances. An online activity was developed to assess the ability of continuing medical education (CME) to improve awareness of the recognition and management of TD among psychiatrists.

Methods

The online CME activity consisted of a 30-minute video discussion between three expert faculty. Educational effect was assessed by comparing a matched sample of psychiatrists’ responses to four identical questions pre- and post-activity. A chi-square test identified significant differences between pre- and post-assessment responses. Cramer’s V was used to calculate the effect size of the online education (≥ 0.16 is considerable). Data were collected between June 26 and August 6, 2019.

Results

Activity participation resulted in a considerable educational effect among psychiatrists (n=739; V=0.25, P<0.001). The following areas showed significant (P <0.05) pre- vs post-educational improvements: recognition of incidence of TD associated with different antipsychotic therapies, differentiation of TD from parkinsonism, and the personalized selection of therapies for the management of TD. 37% of psychiatrists had a measurable increase in confidence in understanding the role of the interprofessional team in recognizing TD after activity participation.

Conclusions

The results indicated that a CME-certified 30-minute video activity was effective at improving knowledge among psychiatrists for the recognition and management of TD. Future education should continue to address best practices in the care of patients with TD.

Funding

Neurocrine Bioscience, Inc
Is this Withdrawal or Intoxication? Case Report Regarding Complications of Unregulated Use of Tianeptine, Etizolam, and Phenibut in the USA
Authors: Ghani Sadia B. , Taylor Eric , Gopalakrishnan Siddesh
Published: May 2021

Background

The internet allows easy access for the sales of psychoactive agents that are not regulated by the FDA. Some of those agents are used to help manage anxiety, depression and sleep, such as tianeptine, etizolam, and phenibut. These medications have the potential for abuse and potentially leading to altered mental status when intoxicated or withdrawing. This presents a challenge to clinicians who may not be aware of availability of such substances. Available literature has discussed the use of above substances individually, but how do you treat if there is use of more than one substance with different mechanisms of actions? Here we present a case of an adult male who has used all three agents simultaneously, leading to a hospital admission.

Case History

A 32-year-old male presented to the emergency department (ED) for altered mental status (AMS). He has a documented history of anxiety but was never treated with prescription medications. No history of substance use was documented. He was self-medicating with concurrent use of tianeptine (atypical antidepressant with mu agonist properties,) phenibut (GABA mimetic) and etizolam (a benzodiazepine-like agent). During his stay, he was agitated and delirious with reports of visual hallucinations. Neuroimaging and lab studies were within normal limits, EEG showed no seizure activity. Over the course of his hospital stay, he was started on Depakote for agitation, a Valium taper for suspected benzodiazepine withdrawal and prevention of seizures, Seroquel for delirium, and baclofen for suspected GABAergic withdrawal symptoms. The patient’s AMS improved and he was discharged on hospital day 10.

Conclusions

This case illustrates the difficulty managing poly-substance use/abuse and stresses the importance for physicians to screen for psychoactive agents purchased over the internet or over the counter to improve treatment outcomes. Continued discussions with patients regarding risks/benefits of use of such substances would be beneficial and help increase awareness.
Discovering Non-Invasive Biomarkers Predictive of Opioid Use Disorder Treatment Response
Authors: Levine Amir , Clemenza Kelly , Weiss Shira , Bisaga Adam , Eitan Erez , Gerra Maria Carla , Donnini Claudia , Gerra Gilberto , Garcia Benjamin
Published: May 2021

Background

Opioid use disorder (OUD) continues to be the driving force behind drug overdoses in the United States, killing nearly 47,000 people in 2018 alone. The increasing presence of deadlier fentanyl analogues in the heroin drug supply are putting users at a greater risk for overdose than ever before. Admissions to treatment programs for OUD have also nearly doubled since 2006, yet relapse rates remain high. In response to these alarming statistics, developing approaches to reduce overdose deaths has become an area of high priority. As it is not yet known which patients are most likely to benefit from a specific treatment, there is a dire need to utilize new molecular tools to guide precision medicine approaches and improve treatment outcomes. Here we describe a proof-of-concept study evaluating plasma-derived extracellular vesicle (EV) signatures and how they differ in patients who responded to two pharmacologically contrasting treatments for OUD: the μOR agonist methadone, and the μOR antagonist naltrexone.

Methods

We obtained blood samples from patients with OUD who remained abstinent from illicit opioids for at least 3 months during treatment with methadone (n=5) and naltrexone (n=5), as well as matched healthy controls (n=5). EVs were isolated from plasma and histones were isolated from peripheral blood mononuclear cells (PBMCs). EVs were then analyzed for lipid and histone post-translational modification (PTM) content using liquid chromatography-mass spectrometry. EV miRNA cargo was determined by RNA sequencing.

Results

We found one lipid class and six miRNAs that differed significantly between the naltrexone group and the methadone and control groups. We also found that histone H3acK9acK14 was increasingly acetylated in PMBCs from both the methadone and naltrexone groups compared to controls.

Discussion

Naltrexone, which is used in treatment of OUD and other substance use disorders as well as disorders of impulse control, was found to have multiple potential corresponding molecular signatures that can be identified after long-term treatment. It remains to be seen if these markers can also be a good predictor for treatment response. In addition, significant gender differences in EV content are found between men and women with OUD, which supports the importance of examining changes in response to treatment in a gender informed way.
Use of a Consultation Service Following Pharmacogenomic Testing in Psychiatry
Authors: Dowd Daniel , Krause David S.
Published: May 2021

Background

There is a plethora of drugs available to psychiatrists for treatment of mental illness, which can vary in efficacy, tolerability, metabolic pathways and drug-drug interactions. Psychotropics are the second most commonly listed therapeutic class mentioned in the FDA’s Table of Pharmacogenomic Biomarkers in Drug Labeling. Pharmacogenomic (PGx) assays are increasingly used in psychiatry to help select safe and appropriate medication for a variety of mental illnesses. Our commercial laboratory offers PGx expert consultations by PharmDs and PhDs to clinician-users. Our database contains valuable information regarding the treatment of a diverse and challenging population.

Methods

Genomind offers a PGx assay currently measuring variants of 24 genes relevant for selection of drugs with a mental illness indication. Since 2012 we have analyzed > 250,000 DNA samples. Between 10/18 - 8/20 6,401 reports received a consult. The data contained herein are derived from those consults. Consultants record information on prior meds, reason for failure or intolerability, potential risk-associated or useful drugs based on the genetic variants. Consultants only recommend specific drugs and doses consistent with a published PGx guideline.

Results

The 5 most commonly discussed genes were SLC6A4, MTHFR, CACNA1C, COMT and BDNF. The 3 most commonly discussed drugs were fluoxetine, lithium and duloxetine. The most common reasons for drug failure were inefficacy and drug induced “agitation, irritability and/or anxiety”. SSRIs were the most common class of discontinued drug; sertraline, escitalopram and fluoxetine were the three most commonly reported discontinuations and were also the 3 most likely to be associated with “no improvement”. Aripiprazole was the most commonly reported discontinued atypical antipsychotic. The providers rated 94% of consultations as extremely or very helpful at the time of consult. An independent validation survey of 128 providers confirmed these ratings, with 96% reporting a rating of “very helpful” or “extremely helpful”. In addition, 94% reported that these consults were superior to PGx consults provided through other laboratories. Patient characteristics captured during consults via a Clinical Global Impressions-Severity (CGI-S) scale revealed that the majority of patients were moderately (54%) or markedly ill (23%). The most frequent symptoms reported were depression, anxiety, insomnia and inattentiveness.

Discussion

The large variety of psychotropic drugs available to providers, and their highly variable response rates, tolerability, capacity for drug-drug interactions and metabolic pathways present a challenge for even expert psychopharmacologists. Consultation with experts in PGx provides additional useful information that may improve outcomes and decrease healthcare resource utilization. This database may provide future opportunities for machine learning algorithms to further inform implications of included gene variants.

Funding

Genomind, Inc.
‘Indian Money’, Intra-Shīʿī Polemics, and the Bohra and Khoja Pilgrimage Infrastructure in Iraq's Shrine Cities, 1897–1932
Authors: O'SULLIVAN MICHAEL
Published: May 2021

Using sources in Arabic, Gujarati, Ottoman, Persian and Urdu, this article examines the foundation of Bohra and Khoja pilgrimage institutions straddling western India and Iraq's Shīʿī shrine cities between 1897 and 1932. As manifestations of ‘locative piety’, these institutions were an outgrowth of the commercial capital Bohra and Khoja merchants had acquired in Indian Ocean trade over the previous half century, and the distinct caste and sectarian identities this wealth augmented. The Bohra and Khoja (both Twelver and Ismāʿīlī) mercantile and religious elites supplied their constituents with a well-ordered pilgrimage to Iraq, certainly by the standards of contemporary Hajj. To achieve this, community-run institutional nodes in Karachi, Bombay and the Shīʿī shrine cities were integrated into wider transport, administrative, and financial infrastructures connecting India and Iraq. Yet at a time when Najaf and Karbala's economic and religious fortunes were plagued by sectarianism, political upheavals and divisions among themujtahids, the growing presence of western Indian Shīʿīs in the shrine cities was fiercely condemned by some Twelver Shīʿī clerics. One of their number, Muḥammad Karīm Khurāsānī, published a substantial polemic against the Bohras and Khojas in 1932, signalling how these pilgrimage infrastructures worked to exacerbate intra-Shīʿī disputes.
Impact of loco-regional treatment including radiotherapy in patients presenting with metastatic breast cancer
Authors: Yadav Budhi Singh , Sunku Rubu , Dahiya Divya
Published: May 2021

Background:

The impact of loco-regional treatment (LRT) with radiotherapy (RT) in patients presenting with metastatic breast cancer (MBC) has not been widely studied. The aim of this study was to review the treatment outcomes of LRT including RT in patients with MBC.

Materials and methods:

Patients who presented with MBC were included in this retrospective study. Analysis was undertaken to determine the difference in local disease control, overall survival (OS) and progression-free survival (PFS) with systemic treatment alone, surgery alone, surgery plus RT and RT alone with long-rank test. Multivariate analysis was done, using the cox regression for factors affecting PFS and OS.

Results:

From 2007 to 2014, data of 257 patients with MBC were collected. Totally, 185 patients received LRT and 72 did not. LRT was surgery plus RT, surgery only and RT only in 113, 47 and 25 patients, respectively. Cytotoxic chemotherapy and hormone therapy were received by 205 and 166 patients, respectively. Median follow-up was 36 months (6–120 months). PFS and OS at 3 years with and without LRT were 31% versus 6% (p < 0·001) and 41% versus 17% (p < 0·001), respectively. PFS at 3 years with surgery plus RT, RT alone and surgery was 40, 33 and 6%, respectively. OS at 3 years with surgery plus RT, RT alone and surgery was 50, 38 and 17%, respectively. Patients without LRT had worse PFS and OS, 6 and 17%, respectively. RT had significant impact on PFS and OS along with chemotherapy and hormone treatment.

Conclusion:

In patients with MBC, improved local control, PFS and OS were achieved with loco-regional RT. Loco-regional RT along with chemotherapy and hormones were significant factors for PFS and OS irrespective of surgery.
Respiratory gating in patients with lung carcinoma undergoing radiotherapy
Authors: Hubers D. , van Dieren E. B. , Woutersen D. P. , Slump C. H.
Published: May 2021

Aim:

This study aims to compare the gating signals of patients with lung cancer recorded during the planning computed tomography scan with the ones recorded during treatment fractions. The results provide insights into how representative the respiratory signals from the planning scan are for radiation dose partitioning.

Materials and methods:

The amplitude and frequency of the respiratory signals of 29 patients with lung carcinoma were analysed and compared with the amplitude and frequency of those recorded during their planning scans. Moreover, a cross-correlation analysis was performed between the difference between the planning scan and fractions and features from the planning scan.

Results:

Two patients showed significantly different amplitude and frequency during treatment fractions compared to those from the planning scan. These patients showed low variances in frequency and amplitude during the different fractions. The difference between planning scan and fractions is correlated with the variances within the planning scan.

Findings:

Respiratory signals can differ between the planning scan and the fractions. In this case, a new planning scan may be beneficial. The respiratory signals from the planning scan may be predictive of whether the planning scan will be representative and usable as a control measure during radiotherapy fractions.
The partisan politics of employment protection legislation: Social democrats, Christian democrats, and the conditioning effect of unemployment
Authors: Zohlnhöfer Reimut , Voigt Linda
Published: May 2021

Political parties are likely to hold differing views about employment protection legislation (EPL). While pro-welfare parties could support EPL, pro-market parties might focus on labour market deregulation. In this paper, we investigate empirically whether partisan politics, especially the government participation of Social democrats and Christian democrats, matter for EPL in 21 established OECD countries from 1985 to 2019. We show that during the golden age of the welfare state, the level of EPL was much higher where Social and Christian democrats dominated the government than elsewhere. After the golden age and under conditions of high unemployment, these unconditional effects mostly disappeared. Instead, the level of unemployment conditions partisan differences. Christian democrats liberalize EPL for regular employment significantly less than other parties under high levels of unemployment. In contrast, Social democrats defend high levels of EPL for regular and temporary employment when unemployment is low. Against expectations, they even liberalize employment protection for labour market insiders more than other parties at very high levels of unemployment.
Dispositional Greed Scales
Authors: Zeelenberg Marcel , Seuntjens Terri G. , van de Ven Niels , Breugelmans Seger M.
Published: May 2021

Abstract. In recent years, different scales have been developed to assess individual differences in dispositional greed. We report two studies ( N1 = 300, N2 = 1,000) on the comparative psychometric properties of these scales. We find that all scales are reliable and that they correlate highly, suggesting that all can be used to assess dispositional greed. Exploratory factor analyses, using the Empirical Kaiser Criterion, the Hull method, and Parallel Analysis as extraction methods, were done on the separate scales and all items together. These analyses reveal that there is quite some consistency in the scales, as in both studies a one-factor solution seems to describe the data best. These results imply that these different scales all assess dispositional greed, although the results also suggest that some items may be deleted from the scales.
Drivers of Phytoplankton Blooms in Hawaii: A Regional Model Study
Authors: Friedrich T. , Powell B. S. , Stock C. A. , Hahn‐Woernle L. , Dussin R. , Curchitser E. N.
Published: May 2021

The region around the main Hawaiian Islands (MHI) is characterized by a permanent thermocline, and numerous processes have been proposed to facilitate phytoplankton blooms in this oligotrophic province. Here, we use a coupled physical‐biogeochemical model of the MHI to elucidate some of the different dynamics behind phytoplankton blooms. The model permits submesoscale processes and is integrated for the years 2010–2017 embedded in a physical state‐estimate reanalysis using nearly 50 million observations. Model results exhibit good agreement between simulated values and observations at Station ALOHA for physical and biogeochemical parameters. The overall levels and the amplitude of the seasonal cycles are well captured for many variables. We show that variations in net primary production are mainly driven by domain‐wide seasonal cycles of light and nitrogen fixers, respectively, as well as short‐lived, stochastic bloom events resulting from the formation of eddies to the west of the island of Hawaii. Furthermore, sporadic wind‐ and current‐driven upwelling is resulting in ephemeral enhancements of nearshore phytoplankton blooms mainly on the northeastern side of the islands.
Cadherin-13 is a critical regulator of GABAergic modulation in human stem-cell-derived neuronal networks
Authors: Mossink Britt , van Rhijn Jon-Ruben , Wang Shan , Linda Katrin , Vitale Maria R. , Zöller Johanna E. M. , van Hugte Eline J. H. , Bak Jitske , Verboven Anouk H. A. , Selten Martijn , Negwer Moritz , Latour Brooke L. , van der Werf Ilse , Keller Jason M. , Klein Gunnewiek Teun M. , Schoenmaker Chantal , Oudakker Astrid , Anania Alessia , Jansen Sophie , Lesch Klaus-Peter , Frega Monica , van Bokhoven Hans , Schubert Dirk , Nadif Kasri Nael
Published: May 2021

Activity in the healthy brain relies on a concerted interplay of excitation (E) and inhibition (I) via balanced synaptic communication between glutamatergic and GABAergic neurons. A growing number of studies imply that disruption of this E/I balance is a commonality in many brain disorders; however, obtaining mechanistic insight into these disruptions, with translational value for the patient, has typically been hampered by methodological limitations.Cadherin-13(CDH13) has been associated with autism and attention-deficit/hyperactivity disorder. CDH13 localizes at inhibitory presynapses, specifically of parvalbumin (PV) and somatostatin (SST) expressing GABAergic neurons. However, the mechanism by which CDH13 regulates the function of inhibitory synapses in human neurons remains unknown. Starting from human-induced pluripotent stem cells, we established a robust method to generate a homogenous population of SST and MEF2C (PV-precursor marker protein) expressing GABAergic neurons (iGABA) in vitro, and co-cultured these with glutamatergic neurons at defined E/I ratios on micro-electrode arrays. We identified functional network parameters that are most reliably affected by GABAergic modulation as such, and through alterations of E/I balance by reduced expression of CDH13 in iGABAs. We found that CDH13 deficiency in iGABAs decreased E/I balance by means of increased inhibition. Moreover, CDH13 interacts with Integrin-β1 and Integrin-β3, which play opposite roles in the regulation of inhibitory synaptic strength via this interaction. Taken together, this model allows for standardized investigation of the E/I balance in a human neuronal background and can be deployed to dissect the cell-type-specific contribution of disease genes to the E/I balance.
The viral hypothesis: how herpesviruses may contribute to Alzheimer’s disease
Authors: Wainberg Michael , Luquez Tain , Koelle David M. , Readhead Ben , Johnston Christine , Darvas Martin , Funk Cory C.
Published: May 2021

The hypothesis that infectious agents, particularly herpesviruses, contribute to Alzheimer’s disease (AD) pathogenesis has been investigated for decades but has long engendered controversy. In the past 3 years, several studies in mouse models, human tissue models, and population cohorts have reignited interest in this hypothesis. Collectively, these studies suggest that many of the hallmarks of AD, like amyloid beta production and neuroinflammation, can arise as a protective response to acute infection that becomes maladaptive in the case of chronic infection. We place this work in its historical context and explore its etiological implications.
Extended real-world experience with the ILUVIEN® (fluocinolone acetonide) implant in the United Kingdom: 3-year results from the Medisoft® audit study
Authors: Bailey Clare , Chakravarthy Usha , Lotery Andrew , Menon Geeta , Talks James ,   for the Medisoft Audit Group
Published: May 2021

Background

This study aimed to assess the long-term effectiveness of the 0.2 μg/day fluocinolone acetonide (FAc) implant over ≥3 years for patients with diabetic macular oedema.

Methods

A retrospective audit of pseudo-anonymised data from patients with chronic diabetic macular oedema (cDMO) and treated with the FAc implant across 14 UK clinical sites. Safety and clinical effectiveness were measured.

Results

Two-hundred and fifty-six eyes had ≥3 years of follow-up (mean 4.28 years), during which a mean of 1.14 FAc implants were used per eye. Mean best-recorded visual acuity (BRVA) increased from 52.6 to 56.7 letters at month 3 and remained stable thereafter; this trend was also seen in pseudophakic eyes. The proportion of patients attaining a BRVA ≥6/12 increased from 17% at baseline to 27% 1 month after FAc implant and remained stable above 30% from month 12 onwards. Eyes with no prior history of intraocular pressure (IOP)-related events required significantly less treatment-emergent IOP-lowering medication than those with a prior history of IOP events (17.9% vs. 50.0% of eyes; p < 0.001). The incidence of an IOP increase of ≥10 mmHg, use of IOP-lowering medication, laser trabeculoplasty and IOP-lowering surgery was 28.9%, 29.7%, 0.8% and 2.7%, respectively, for the whole cohort. There were significant reductions in mean central foveal thickness and macular volume (p < 0.001).

Conclusions

The FAc implant was well tolerated, with predictable and manageable IOP-related events while delivering a continuous microdose of corticosteroid to eyes with cDMO, providing prolonged vision preservation and a reduced number of treatments.
Capturing the clinical decision-making processes of expert and novice diabetic retinal graders using a ‘think-aloud’ approach
Authors: Curran Katie , Congdon Nathan , Peto Tunde , Dardis Catherine , Nguyen Quan Nhu , Hoang Tung Thanh , Bannon Finian , Luu An , Mai Tung Quoc , Nguyen Van Thu , Thi Nguyen Hue , Tran Huong , Tran Hoang Huy , Lohfeld Lynne
Published: May 2021

Background

Diabetic eye screening programmes have been developed worldwide based on evidence that early detection and treatment of diabetic retinopathy are crucial to preventing sight loss. However, little is known about the decision-making processes and training needs of diabetic retinal graders, particularly in low- and middle-income countries.

Objectives

To provide data for improving evidence-based diabetic retinopathy training to help novice graders process fundus images more like experts.

Subjects/methods

This is a mixed-methods qualitative study conducted in southern Vietnam and Northern Ireland. Novice diabetic retinal graders in Vietnam (n = 18) and expert graders in Northern Ireland (n = 5) were selected through a purposive sampling technique. Data were collected from 21st February to 3rd September 2019. The interviewer used neutral prompts during think-aloud sessions to encourage participants to verbalise their thought processes while grading fundus images from anonymised patients, followed by semi-structured interviews. Thematic framework analysis was used to identify themes, supported by illustrative quotes from interviews. Mann–Whitney U tests were used to compare graders’ performance.

Results

Expert graders used a more systematic approach when grading images, considered all four images per patient and used available software tools such as red-free filters prior to making a decision on management. The most challenging features for novice graders were intra-retinal microvascular abnormalities and new vessels, which were more accurately identified by experts.

Conclusion

Taking more time to grade fundus images and adopting a protocol-driven “checklist” approach may help novice graders to function more like experts.
Automatic wavelet-based 3D nuclei segmentation and analysis for multicellular embryo quantification
Authors: Wu Tzu-Ching , Wang Xu , Li Linlin , Bu Ye , Umulis David M.
Published: May 2021

Identification of individual cells in tissues, organs, and in various developing systems is a well-studied problem because it is an essential part of objectively analyzing quantitative images in numerous biological contexts. We developed a size-dependent wavelet-based segmentation method that provides robust segmentation without any preprocessing, filtering or fine-tuning steps, and is robust to the signal-to-noise ratio. The wavelet-based method achieves robust segmentation results with respect to True Positive rate, Precision, and segmentation accuracy compared with other commonly used methods. We applied the segmentation program to zebrafish embryonic development IN TOTO for nuclei segmentation, image registration, and nuclei shape analysis. These new approaches to segmentation provide a means to carry out quantitative patterning analysis with single-cell precision throughout three dimensional tissues and embryos and they have a high tolerance for non-uniform and noisy image data sets.
The effects of the exposure to neurotoxic elements on Italian schoolchildren behavior
Authors: Renzetti Stefano , Cagna Giuseppa , Calza Stefano , Conversano Michele , Fedrighi Chiara , Forte Giovanni , Giorgino Augusto , Guazzetti Stefano , Majorani Costanza , Oppini Manuela , Peli Marco , Petrucci Francesco , Pino Anna , Placidi Donatella , Senofonte Oreste , Zoni Silvia , Alimonti Alessandro , Lucchini Roberto G.
Published: May 2021

Neurodevelopmental disorders are constantly increasing on a global scale. Some elements like heavy metals are known to be neurotoxic. In this cross-sectional study we assessed the neurobehavioral effect of the exposure to trace elements including lead, mercury, cadmium, manganese, arsenic and selenium and their interactions among 299 schoolchildren residing in the heavily polluted Taranto area in Italy. Whole blood, urine and hair were collected for metal analyses, while the Child Behavior Checklist and the Social Responsiveness Scale, administered to the main teacher and the mothers were considered to identify behavioral problems in children. Blood lead mainly influenced social problems, aggressive behavior, externalizing and total problems. Urinary arsenic showed an impact on anxiety and depression, somatic problems, attention problems and rule breaking behavior. A significant interaction between lead and arsenic was observed, with a synergistic effect of the two metals increasing the risk of attention problems, aggressive behavior, externalizing problems and total problems. Overall, we were able to test that higher blood lead, urinary arsenic concentrations and their interaction increase the risk of neurobehavioral problems. This is in line with the U.S. Environmental Protection Agency’s priority list of hazardous substances where arsenic and lead are ranked as first and second respectively.
Selection and validation of appropriate reference genes for RT-qPCR analysis of flowering stages and different genotypes of Iris germanica L
Authors: Wang Yinjie , Zhang Yongxia , Liu Qingquan , Tong Haiying , Zhang Ting , Gu Chunsun , Liu Liangqin , Huang Suzhen , Yuan Haiyan
Published: May 2021

Iris germanica L. is a perennial herbaceous plant that has been widely cultivated worldwide and is popular for its elegant and vibrantly colorful flowers. Selection of appropriate reference genes is the prerequisite for accurate normalization of target gene expression by quantitative real-time PCR. However, to date, the most suitable reference genes for flowering stages have not been elucidated in I. germanica. In this study, eight candidate reference genes were examined for the normalization of RT-qPCR in three I. germanica cultivars, and their stability were evaluated by four different algorithms (GeNorm, NormFinder, BestKeeper, and Ref-finder). The results revealed that IgUBC and IgGAPDH were the most stable reference genes in ‘00246’ and ‘Elizabeth’, and IgTUB and IgUBC showed stable expression in ‘2010200’. IgUBC and IgGAPDH were the most stable in all samples, while IgUBQ showed the least stability. Finally, to validate the reliability of the selected reference genes, the expression patterns of IgFT (Flowering Locus T gene) was analyzed and emphasized the importance of appropriate reference gene selection. This work presented the first systematic study of reference genes selection during flower bud development and provided guidance to research of the molecular mechanisms of flowering stages in I. germanica.
Bortezomib induces methylation changes in neuroblastoma cells that appear to play a significant role in resistance development to this compound
Authors: Łuczkowska Karolina , Sokolowska Katarzyna Ewa , Taryma-Lesniak Olga , Pastuszak Krzysztof , Supernat Anna , Bybjerg-Grauholm Jonas , Hansen Lise Lotte , Paczkowska Edyta , Wojdacz Tomasz K. , Machaliński Bogusław
Published: May 2021

The anticancer activity of bortezomib (BTZ) has been increasingly studied in a number of indications and promising results for the use of this treatment have been shown in neuroblastoma. As BTZ treatment is usually administered in cycles, the development of resistance and side effects in patients undergoing therapy with BTZ remains a major challenge for the clinical usage of this compound. Common resistance development also means that certain cells are able to survive BTZ treatment and bypass molecular mechanisms that render BTZ anticancer activity. We studied the methylome of neuroblastoma cells that survived BTZ treatment. Our results indicate that BTZ induces pronounced genome wide methylation changes in cells which recovered from the treatment. Functional analyses of identified methylation changes demonstrated they were involved in key cancer pathology pathways. These changes may allow the cells to bypass the primary anticancer activity of BTZ and develop a treatment resistant and proliferative phenotype. To study whether cells surviving BTZ treatment acquire a proliferative phenotype, we repeatedly treated cells which recovered from the first round of BTZ treatment. The repetitive treatment led to induction of the extraordinary proliferative potential of the cells, that increased with subsequent treatments. As we did not observe similar effects in cells that survived treatment with lenalidomide, and non-treated cells cultured under the same experimental conditions, this phenomenon seems to be BTZ specific. Overall, our results indicate that methylation changes may play major role in the development of BTZ resistance.
Searching for pneumothorax in x-ray images using autoencoded deep features
Authors: Sze-To Antonio , Riasatian Abtin , Tizhoosh H. R.
Published: May 2021

Fast diagnosis and treatment of pneumothorax, a collapsed or dropped lung, is crucial to avoid fatalities. Pneumothorax is typically detected on a chest X-ray image through visual inspection by experienced radiologists. However, the detection rate is quite low due to the complexity of visual inspection for small lung collapses. Therefore, there is an urgent need for automated detection systems to assist radiologists. Although deep learning classifiers generally deliver high accuracy levels in many applications, they may not be useful in clinical practice due to the lack of high-quality and representative labeled image sets. Alternatively, searching in the archive of past cases to find matching images may serve as a “virtual second opinion” through accessing the metadata of matched evidently diagnosed cases. To use image search as a triaging or diagnosis assistant, we must first tag all chest X-ray images with expressive identifiers, i.e., deep features. Then, given a query chest X-ray image, the majority vote among the top k retrieved images can provide a more explainable output. In this study, we searched in a repository with more than 550,000 chest X-ray images. We developed the Autoencoding Thorax Net (short AutoThorax -Net) for image search in chest radiographs. Experimental results show that image search based on AutoThorax -Net features can achieve high identification performance providing a path towards real-world deployment. We achieved 92% AUC accuracy for a semi-automated search in 194,608 images (pneumothorax and normal) and 82% AUC accuracy for fully automated search in 551,383 images (normal, pneumothorax and many other chest diseases).
Southward growth of Mauna Loa’s dike-like magma body driven by topographic stress
Authors: Varugu Bhuvan , Amelung Falk
Published: May 2021

Space-geodetic observations of a new period of inflation at Mauna Loa volcano, Hawaii, recorded an influx of 0.11 km3 of new magma into it’s dike-like magma body during 2014–2020. The intrusion started after at least 4 years of decollement slip under the eastern flank creating > 0.15 MPa opening stresses in the rift zone favorable for magma intrusion. Volcanoes commonly respond to magma pressure increase with the injection of a dike, but Mauna Loa responded with lateral growth of its magma body in the direction of decreasing topographic stress. In 2017, deformation migrated back, and inflation continued at the pre-2015 location. Geodetic inversions reveal a 8 × 8.5, 10 × 3 and 9 × 4 km2 dike-like magma body during the 2014–2015, 2015–2018 and 2018–2020 periods, respectively, and an average decollement slip of ~ 23 cm/year along a 10 × 5 km2 fault. The evolution of the dike-like magma body including the reduction in vertical extent is consistent with a slowly ascending dike propagating laterally when encountering a stress barrier and freezing its tip when magma influx waned. Overall, the magma body widened about 4.5 m during 2002–2020.
Environmental determinants of COVID-19 transmission across a wide climatic gradient in Chile
Authors: Correa-Araneda Francisco , Ulloa-Yáñez Alfredo , Núñez Daniela , Boyero Luz , Tonin Alan M. , Cornejo Aydeé , Urbina Mauricio A. , Díaz María Elisa , Figueroa-Muñoz Guillermo , Esse Carlos
Published: May 2021

Several studies have examined the transmission dynamics of the novel COVID-19 disease in different parts of the world. Some have reported relationships with various environmental variables, suggesting that spread of the disease is enhanced in colder and drier climates. However, evidence is still scarce and mostly limited to a few countries, particularly from Asia. We examined the potential role of multiple environmental variables in COVID-19 infection rate [measured as mean relative infection rate = (number of infected inhabitants per week / total population) × 100.000) from February 23 to August 16, 2020 across 360 cities of Chile. Chile has a large climatic gradient (≈ 40º of latitude, ≈ 4000 m of altitude and 5 climatic zones, from desert to tundra), but all cities share their social behaviour patterns and regulations. Our results indicated that COVID-19 transmission in Chile was mostly related to three main climatic factors (minimum temperature, atmospheric pressure and relative humidity). Transmission was greater in colder and drier cities and when atmospheric pressure was lower. The results of this study support some previous findings about the main climatic determinants of COVID-19 transmission, which may be useful for decision-making and management of the disease.
Cyclooxygenase-2 induces neoplastic transformation by inhibiting p53-dependent oncogene-induced senescence
Authors: Lee Hyeon Ju , Kim So Ra , Jung Yu-Jin , Han Jeong A.
Published: May 2021

Much in vivo evidence indicates that cyclooxygenase-2 (COX-2) is deeply involved in tumorigenesis. Although it has been proposed that COX-2-derived pro-inflammatory prostanoids mediate the tumorigenic activity of COX-2, the tumorigenic mechanisms of COX-2 are not yet fully understood. Here, we investigated the mechanism by which COX-2 causes transformation from normal cells to malignant cells by using normal murine or human cells. We found that COX-2 inhibits the pro-senescent function of p53 under oncogenic RAS activation, by which it prevents oncogene-induced senescence (OIS) and induces neoplastic transformation. We also found that COX-2 physically interacts with p53 in the nucleus under oncogenic RAS activation, and that this COX-2-p53 interaction rather than the catalytic activity is involved in the COX-2-mediated inhibition of the pro-senescent function of p53 and OIS, and induction of neoplastic transformation. These findings strongly suggest that the oncogenic property of COX-2 is closely related to its ability to inactivate p53 under strong mitogenic signals, and that aberrant activation of the COX-2/a mitogenic oncogene combination can be a potent driving force for tumorigenesis. This study might contribute to our understanding of the molecular basis for the tumorigenic activity of COX-2 and the development of novel anti-tumor drugs targeting COX-2-p53 interactions.
Atherogenic index of plasma as predictors for metabolic syndrome, hypertension and diabetes mellitus in Taiwan citizens: a 9-year longitudinal study
Authors: Li Yen-Wei , Kao Tung-Wei , Chang Pi-Kai , Chen Wei-Liang , Wu Li-Wei
Published: May 2021

Deeply involved with dyslipidemia, cardiovascular disease has becoming the leading cause of mortality since the early twentieth century in the modern world. Whose correlation with metabolic syndrome (MetS), hypertension and type 2 diabetes mellitus (T2DM) has been well established. We conducted a 9-year longitudinal study to identify the association between easily measured lipid parameters, future MetS, hypertension and T2DM by gender and age distribution. Divided into three groups by age (young age: < 40, middle age: ≥ 40 and < 65 and old age: ≥ 65), 7670 participants, receiving standard medical inspection at Tri-Service General Hospital (TSGH) in Taiwan, had been enrolled in this study. Atherogenic index of plasma (AIP) was a logarithmically transformed ratio of triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C). Through multivariate regression analyses, the hazard ratio (HR) of AIP for MetS, hypertension and T2DM were illustrated. AIP revealed significant association with all the aforementioned diseases through the entire three models for both genders. Additionally, AIP revealed significant correlation which remained still after fully adjustment in MetS, hypertension, and T2DM groups for subjects aged 40–64-year-old. Nevertheless, for participants aged above 65-year-old, AIP only demonstrated significant association in MetS group. Our results explore the promising value of AIP to determine the high-risk subjects, especially meddle-aged ones, having MetS, hypertension, and T2DM in the present and the future.
Formulation and evaluation of injectable dextran sulfate sodium nanoparticles as a potent antibacterial agent
Authors: Madkhali Osama A. , Sivagurunathan Moni Sivakumar , Sultan Muhammad H. , Bukhary Haitham A. , Ghazwani Mohammed , Alhakamy Nabil A. , Meraya Abdulkarim M. , Alshahrani Saeed , Alqahtani Saad Saeed , Bakkari Mohammed Ali , Alam M. Intakhab , Elmobark Mohamed Eltaib
Published: May 2021

The purpose of this study was to develop a novel nano antibacterial formulation of dextran sulfate sodium polymer. The dextran sulfate sodium (DSS) nanoparticles were formulated with gelation technique. The nanoparticles exhibited significant physicochemical and effective antibacterial properties, with zeta potential of − 35.2 mV, particle size of 69.3 z d nm, polydispersity index of 0.6, and percentage polydispersity of 77.8. The DSS nanoparticles were stable up to 102 °C. Differential scanning calorimetry revealed an endothermic peak at 165.77 °C in 12.46 min, while XRD analysis at 2θ depicted various peaks at 21.56°, 33.37°, 38.73°, 47.17°, 52.96°, and 58.42°, indicating discrete nanoparticle formation. Antibacterial studies showed that the DSS nanoparticles were effective against Gram-positive and Gram-negative bacteria. The minimum inhibitory concentrations of DSS nanoparticles for Bacillus subtilis (B. subtilis), Staphylococcus aureus (S. aureus), Streptococcus pyogenes (S. pyogenes), Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa), Klebsiella pneumoniae (K. pneumoniae) and Proteus vulgaris (P. vulgaris) were 150, 200, 250, 150, 200, 250, 250 µg/mL, respectively. The antibacterial effects of DSS nanoparticles were in the order E. coli (26 ± 1.2 mm) at 150 µg/mL > S. pyogenes (24.6 ± 0.8 mm) at 250 µg/mL > B. subtilis (23.5 ± 2 mm) at 150 µg/mL > K. pneumoniae (22 ± 2 mm) at 250 µg/mL > P. aeruginosa (21.8 ± 1 mm) at 200 µg/mL > S. aureus (20.8 ± 1 mm) at 200 µg/mL > P. vulgaris (20.5 ± 0.9 mm) at 250 µg/mL. These results demonstrate the antibacterial potency of DSS injectable nanoparticles.
Development of genic SSR marker resources from RNA-seq data in Camellia japonica and their application in the genus Camellia
Authors: Li Qingyuan , Su Xiaojun , Ma Huanhuan , Du Kebing , Yang Min , Chen Baolin , Fu Shao , Fu Tianjing , Xiang Conglin , Zhao Qing , Xu Lin
Published: May 2021

Camelliais a genus of flowering plants in the family Theaceae, and several species in this genus have economic importance. Although a great deal of molecular makers has been developed for molecular assisted breeding in genusCamelliain the past decade, the number of simple sequence repeats (SSRs) publicly available for plants in this genus is insufficient. In this study, a total of 28,854 potential SSRs were identified with a frequency of 4.63 kb. A total of 172 primer pairs were synthesized and preliminarily screened in 10C. japonicaaccessions, and of these primer pairs, 111 were found to be polymorphic. Fifty-one polymorphic SSR markers were randomly selected to perform further analysis of the genetic relationships of 89 accessions across the genusCamellia. Cluster analysis revealed major clusters corresponding to those based on taxonomic classification and geographic origin. Furthermore, all the genotypes ofC. japonicaseparated and consistently grouped well in the genetic structure analysis. The results of the present study provide high-quality SSR resources for molecular genetic breeding studies in camellia plants.
Magneto-optical borogermanate glasses and fibers containing Tb3+
Authors: Franco Douglas F. , Ledemi Yannick , Correr Wagner , Morency Steeve , Afonso Conrado R. M. , Messaddeq Sandra H. , Messaddeq Younès , Nalin Marcelo
Published: May 2021

New glass compositions containing high concentrations of Tb3+ ions were developed aiming at the production of magneto-optical (MO) fibers. This work reports on the structural and MO properties of a new glass composition based on (100 − x)(41GeO2–25B2O3–4Al2O3–10Na2O–20BaO) − xTb4O7. Morphological analysis (HR-TEM) of the sample with the highest concentration of Tb3+ ions confirmed the homogeneous distribution of Tb3+ ions and the absence of nanoclusters. All the samples presented excellent thermal stability against crystallization (ΔT > 100 °C). An optical fiber was manufactured by a fiber drawing process. The UV–Vis spectra of the glasses showed Tb3+ electronic transitions and optical windows varying from 0.4 to 1.6 μm. The magneto-optical properties and the paramagnetic behaviors of the glasses were investigated using Faraday rotation experiments. The Verdet constant (VB) values were calculated at 500, 650, 880, 1050, 1330, and 1550 nm. The maximum VB values obtained at 650 and 1550 nm for the glass with x = 18 mol% were -128 and − 17.6 rad T−1 m−1, respectively. The VB values at 500 and 1550 nm for the optical fiber containing 8 mol% of Tb4O7 were − 110.2 and − 9.5 rad T−1 m−1, respectively, while the optical loss at around 880 nm was 6.4 dB m−1.