bluuebunny/crossref_metadata_2025 huggingface dataset:
Left atrial evaluation by cardiovascular magnetic resonance: sensitive and unique biomarkers
Authors: Peters Dana C , Lamy Jérôme , Sinusas Albert J , Baldassarre Lauren A
Published: October 2021

Left atrial (LA) imaging is still not routinely used for diagnosis and risk stratification, although recent studies have emphasized its importance as an imaging biomarker. Cardiovascular magnetic resonance is able to evaluate LA structure and function, metrics that serve as early indicators of disease, and provide prognostic information, e.g. regarding diastolic dysfunction, and atrial fibrillation (AF). MR angiography defines atrial anatomy, useful for planning ablation procedures, and also for characterizing atrial shapes and sizes that might predict cardiovascular events, e.g. stroke. Long-axis cine images can be evaluated to define minimum, maximum, and pre-atrial contraction LA volumes, and ejection fractions (EFs). More modern feature tracking of these cine images provides longitudinal LA strain through the cardiac cycle, and strain rates. Strain may be a more sensitive marker than EF and can predict post-operative AF, AF recurrence after ablation, outcomes in hypertrophic cardiomyopathy, stratification of diastolic dysfunction, and strain correlates with atrial fibrosis. Using high-resolution late gadolinium enhancement (LGE), the extent of fibrosis in the LA can be estimated and post-ablation scar can be evaluated. The LA LGE method is widely available, its reproducibility is good, and validations with voltage-mapping exist, although further scan–rescan studies are needed, and consensus regarding atrial segmentation is lacking. Using LGE, scar patterns after ablation in AF subjects can be reproducibly defined. Evaluation of ‘pre-existent’ atrial fibrosis may have roles in predicting AF recurrence after ablation, predicting new-onset AF and diastolic dysfunction in patients without AF. LA imaging biomarkers are ready to enter into diagnostic clinical practice.
Environmental identity economics: an application to farmers’ pro-environmental investment behaviour
Authors: Zemo Kahsay Haile , Termansen Mette
Published: October 2021

This study proposes an environmental identity economics theory that can improve our understanding of pro-environmental behaviour. We test the potential of the theory by analysing farmers’ decisions to invest in renewable energy production using a hybrid choice model. Our findings illustrate that farmers with a strong environmental identity require less financial incentive to invest. Furthermore, lower compensation is found to be sufficient to induce farmers with a strong environmental identity to commit to more binding investment contracts. Our findings stress the need for differentiated designs of agri-environmental programmes and mechanisms that enhance farmers’ environmental identity.
Undocumented Older Latino Immigrants in the United States: Population Projections and Share of Older Undocumented Latinos by Health Insurance Coverage and Chronic Health Conditions, 2018–2038
Authors: Ro Annie , Van Hook Jennifer , Walsemann Katrina M
Published: October 2021

Objectives

This article focuses on the older Latino undocumented population and anticipates how their current demographic characteristics and health insurance coverage might affect future population size and health insurance trends.

Methods

We use the 2013–2018 American Community Survey as a baseline to project growth in the Latino 55 and older undocumented population over the next 20 years. We use the cohort component method to estimate population size across different migration scenarios and distinguish between aging in place and new immigration. We also examine contemporary health insurance coverage and chronic health conditions among 55 and older undocumented Latinos from the 2003–2014 California Health Interview Survey. We then project health insurance rates in 2038 among Latino immigrants under different migration and policy scenarios.

Results

If current mortality, migration, and policy trends continue, projections estimate that 40% of undocumented Latino immigrants will be 55 years or older by 2038—nearly all of whom will have aged in place. Currently, 40% of older Latino undocumented immigrants do not have insurance. Without policies that increase access to insurance, projections estimate that the share who are uninsured among all older Latinos immigrants will rise from 15% to 21%, and the share who is both uninsured and living with a chronic health condition will rise from 5% to 9%.

Discussion

Without access to health care, older undocumented immigrants may experience delayed care and more severe morbidity. Our projections highlight the need to develop and enact policies that can address impending health access concerns for an increasingly older undocumented Latino population.
Management of spontaneous pneumothorax in patients with COVID-19
Authors: Ulutas Hakki , Celik Muhammet Reha , Gulcek Ilham , Kalkan Muhammed , Agar Mehmet , Kilic Talat , Gulcek Emine
Published: October 2021

OBJECTIVES

The coronavirus disease 2019 (COVID-19) pneumonia may cause cystic features of lung parenchyma which can resolve or progress to larger blebs. Pneumothorax was more likely in patients with neutrophilia, severe lung injury and a prolonged clinical course. The timely diagnosis and management will reduce COVID-19-associated morbidity and mortality.

METHODS

We present 11 cases of spontaneous pneumothorax managed with chest tube thoracostomy or high-dose oxygen therapy. Isolated spontaneous pneumothorax was detected in all cases.

RESULTS

Eight cases were male and 3 cases were female. There were bilateral ground-glass opacities or pulmonary infiltrates in the parenchyma of the 10 cases. We detected neutrophilia, lymphopaenia and increased C-reactive protein, Ferritin, lactate dehydrogenase, D-Dimer, interleukin-6 levels in almost all cases. Chest tube thoracostomy was sufficient to treat pneumothorax in our 9 of case. In 2 cases, pneumothorax healed with high-dose oxygen therapy. Favipiravir and antibiotic treatment were given to different 10 patients. In our institution, all patients with COVID-19 infection were placed on prophylactic or therapeutic anticoagulation, unless contraindicated. The treatments of patients diagnosed with secondary spontaneous pneumothorax during the pandemic period and those diagnosed with secondary spontaneous pneumothorax in the previous 3 years were compared with the durations of tube thoracostomy performed in both groups.

CONCLUSIONS

The increased number of cases of pneumothorax suggests that pneumothorax may be a complication of COVID-19 infection. During medical treatment of COVID-19, pneumothorax may be the only reason for hospitalization. Although tube thoracostomy is a sufficient treatment option in most cases, clinicians should be aware of the difficulties that may arise in diagnosis and treatment.
Midterm survival of imaging-assisted robotic lung segmentectomy for non-small-cell lung cancer
Authors: Chaari Zied , Montagne François , Sarsam Matthieu , Bottet Benjamin , Rinieri Philippe , Gillibert Andre , Baste Jean Marc
Published: October 2021

OBJECTIVES

Our goal was to report our midterm results using imaging-assisted modalities with robotic segmentectomies for non-small-cell lung cancer (NSCLC).

METHODS

This was a retrospective study of all robotic segmentectomies, with confirmed NSCLC, performed at our general and thoracic surgery unit in the Rouen University Hospital (France), from January 2012 through December 2019. Benign and metastatic lesions were excluded. Data were extracted from the EPITHOR French nationwide database.

RESULTS

A total of 121 robotic segmentectomies were performed for 118 patients with a median age of 65 (interquartile range: 60, 69) years. The majority had clinical stage T1aN0M0 (71.9%) or T1bN0M0 (13.2%). The mean (standard deviation) number of resected segments was 1.93 (1.09) with 80.2% imaging-assisted segmentectomies. Oriented (according to tumour location) or systematic lymphadenectomy or sampling was performed for 72.7%, 23.1% and 4.1% of patients. The postoperative course was uneventful for 94 patients (77.7%), whereas 34 complications occurred for 27 patients (22.3%), including 2 patients (1.7%) with Clavien-Dindo ≥III complications. The mean thoracic drainage duration was 4.12 days, and the median hospital stay was 4 days (interquartile range: 3, 5) after the operation. The 2-year survival rate was 93.9% (95% confidence interval: 86.4–97.8%). Excluding stage IV (n = 3) and stage 0 tumours (n = 6), the 2-year survival rate was 95.7% (95% confidence interval: 88.4–98.8%) compared to an expected survival rate of 94.0% according to stage-specific survival rates found in a large external reference cohort.

CONCLUSIONS

Imaging-guided robotic-assisted thoracic surgery segmentectomy seems to be useful and oncological with good midterm results, especially for patients with early-stage NSCLC.
Varentropy of inactivity time of a random variable and its related applications
Authors: Raqab Mohammad Z , Bayoud Husam A , Qiu Guoxin
Published: October 2021

The information content of a random variable is of importance in the field of information theory. The mean and the variance of the information content of a random variable are called entropy and varentropy of this random variable, respectively. The varentropy of the inactivity time of a random variable is studied and termed by past varentropy in this paper. Reliability properties associated with the past varentropy and the reversed hazard rate function are discussed. Lower and upper bounds for the past varentropy are provided. The varentropy is applied for the proportional reversed hazard rate model. Also, asymptotic distribution for the information content of the inactivity time of a random variable is provided based on past entropy and varentropy.
Autoantibodies in Common Connective Tissue Diseases: A Primer for Laboratory Professionals
Authors: Martin Janet , Petryayeva Eleonora , Khan Waliul I
Published: October 2021

Background

Autoimmune connective tissue disorders are a significant health concern throughout the world with an estimated prevalence of 3% to 5%. They are associated with a variety of autoantibodies that play roles in their diagnosis, risk stratification, prognostication, and/or management. While some autoantibodies have been well-characterized for use in clinical laboratories, many more are in the research stage. Rapid transition from research to clinical practice, lack of clinical guidelines, and harmonization across a rapidly growing number of commercially available tests create numerous challenges to clinicians and laboratories.

Content

This article briefly discusses common connective tissue disorders and their association with well-known autoantibodies, describes current methods used in clinical laboratories, and outlines their advantages and limitations in the context of these diseases.

Understanding the role of specific autoantibodies and various methodologies for autoantibody testing are important for laboratory professionals who may be introducing/repatriating new tests, updating existing tests, or advising clinicians/patients about testing options/results. Collaboration between laboratory professional staff and clinicians, around the advantages and limitations of each methodology, is also important in their appropriate clinical utilization.
Emergency Response Validation of the Soleris® Direct Yeast and Mold Method for Detection of Yeast and Mold in Dried Cannabis Flower: AOAC Performance Tested MethodSM 051301
Authors: Le Quynh-Nhi , Montei Carolyn , Mozola Mark , Roman Brooke , Biswas Preetha , Donofrio Robert
Published: October 2021

Background

Soleris® Direct Yeast and Mold (DYM) is a growth-based, automated method for detection of yeast and mold in select foods and other sample types including nutraceuticals and cosmetics. The Soleris method is used in a “dilute-to-specification” or threshold manner in which a result is scored as positive or negative around a predetermined cutoff (in CFU/g) established by the dilution and volume of sample homogenate tested.

Objective

The objective of this study was to validate the method for testing of dried cannabis flower. The validation was conducted under the Emergency Response Validation program of the AOAC Research Institute.

Method

The study included inclusivity and exclusivity testing, in particular testing of yeast and mold species associated with cannabis, and a matrix study in which Soleris method presumptive results were compared with Soleris confirmed results using Dichloran Rose-Bengal Chloramphenicol (DRBC) agar for confirmation. Samples at four different levels of natural yeast and mold contamination were tested at two test thresholds.

Results

In inclusivity testing, all 63 yeast and mold strains tested produced positive results within the specified test duration of 72 h. In exclusivity testing, 36 of 37 strains tested produced no detection within 72 h. In matrix testing, there were no significant differences between Soleris presumptive and confirmed results for any contamination level or test threshold as determined by probability of detection analysis.

Conclusions

Results indicate that the Soleris method is an effective procedure for detection of yeast and mold in dried cannabis flower.

Highlights

With the Soleris method, results are available within 72 h compared with the 5–7 days required for microbiological culture methods.
Behavioral Effects and Retention of Protein Immunomarkers on Plum Curculio Conotrachelus nenuphar (Coleoptera: Curculionidae)
Authors: Lampasona Timothy , Acebes-Doria Angelita , Leskey Tracy C , Nielsen Anne L
Published: October 2021

Protein immunomarking can be used to track the dispersal of insects in the field or identify plant–insect interactions. By marking insects with known proteins and recapturing them, their movement or host use can be quantified with Enzyme Linked Immunosorbent Assay (ELISA). Before using this technique, retention and behavioral effects of these markers should be evaluated to ensure that the insect’s natural behaviors are conserved. Here, we tested the effects of protein markers on the plum curculio, Conotrachelus nenuphar (Coleoptera: Curculionidae) using two different application methods. This weevil is native to North American and a pest of tree fruit and blueberry in the United States and causes damage resulting in near complete crop loss if left untreated. We tested the effects of marking adult C. nenuphar with two inexpensive food-based immunoprotein markers, bovine casein (cow’s milk) and chicken albumin (egg whites) on climbing distance (total cm), lateral movement (total cm), and lateral movement speed (cm/s), as well as retention time of protein immunomarkers. Neither protein immunomarker affected C. nenuphar movement or climbing, although females climbed significantly greater distances than males. ELISA assays detected 37.5–56.2% of milk protein and 56.2–59.3% of egg on the insect 7 d after application depending on application method. Our findings indicate that food-based protein immunomarkers can be used in future studies to test C. nenuphar movement within host plants without impacting behavior. The use of protein immunomarking will allow studies that will lead to behaviorally based management tactics.
Subacute fat embolism syndrome in a young female trauma patient during COVID-19
Authors: Nixon Mickaela J , Grant Thomas
Published: October 2021

We report the symptom evolution of a young female trauma patient leading to a diagnosis of fat embolism syndrome (FES). Twenty-four hours post-trauma she developed respiratory distress, followed by transient neurological compromise and later petechia. The subtle and fluctuating nature of her presentation made the diagnosis via existing clinical criteria challenging, as did the lack of specificity of thoracic computerized tomography due to the concurrent coronavirus (COVID-19) pandemic. Making the diagnosis was important as it changed the patient’s management, likely preventing a diagnosis in extremis. This case emphasizes the importance of maintaining a high clinical suspicion of FES in any (poly)trauma patient. This is especially true during COVID-19, as correctly identifying non-COVID-19 causes of respiratory failure will prevent additional pandemic victims. In addition, this case supports the need for a diagnostic approach that balances clinical, biochemical and imaging features and takes a cumulative approach in order to identify subacute FES.
How can we manage Bezold abscess emergency in COVID-19 pandemic? Blind ceftriaxone and metronidazole treatment to avoid infection spread†
Authors: Scarpa Alfonso , Di Stadio Arianna , De Luca Pietro , Calvanese Matteo , Viola Pasquale , Tassone Domenico , de Campora Luca , Simone Matteo , Ricci Giampietro , Messineo Daniela , Ralli Massimo , Cassandro Claudia
Published: October 2021

Bezold abscess (BA) can be a rare complication of different forms of otitis media. We describe a rare case of BA determined by Escherichia Coli. Because of COVID-19 restriction, the surgery had to be delayed up to the swab results. To avoid infection spread, the patient was treated by blind antibiotic treatment until the surgical drainage of mastoid and neck. Thanks to the treatment with broad-spectrum antibiotics, the progression and the spread of the infection during COVID-19 investigation was avoided. Delayed surgery could expose the patient to the risk of severe brain infection caused by the E. Coli.
The formation of wide exoKuiper belts from migrating dust traps
Authors: Miller E , Marino S , Stammler S M , Pinilla P , Lenz C , Birnstiel T , Henning Th
Published: October 2021

The question of what determines the width of Kuiper belt analogues (exoKuiper belts) is an open one. If solved, this understanding would provide valuable insights into the architecture, dynamics, and formation of exoplanetary systems. Recent observations by ALMA have revealed an apparent paradox in this field, the presence of radially narrow belts in protoplanetary discs that are likely the birthplaces of planetesimals, and exoKuiper belts nearly four times as wide in mature systems. If the parent planetesimals of this type of debris disc indeed form in these narrow protoplanetary rings via streaming instability where dust is trapped, we propose that this width dichotomy could naturally arise if these dust traps form planetesimals whilst migrating radially, e.g. as caused by a migrating planet. Using the dust evolution software dustpy, we find that if the initial protoplanetary disc and trap conditions favour planetesimal formation, dust can still effectively accumulate and form planetesimals as the trap moves. This leads to a positive correlation between the inward radial speed and final planetesimal belt width, forming belts up to ∼100au over 10 Myr of evolution. We show that although planetesimal formation is most efficient in low-viscosity (α = 10−4) discs with steep dust traps to trigger the streaming instability, the large widths of most observed planetesimal belts constrain α to values ≥4 × 10−4 at tens of au, otherwise the traps cannot migrate far enough. Additionally, the large spread in the widths and radii of exoKuiper belts could be due to different trap migration speeds (or protoplanetary disc lifetimes) and different starting locations, respectively. Our work serves as a first step to link exoKuiper belts and rings in protoplanetary discs.
CALIBRATION METHOD AND ABSOLUTE MEASUREMENTS OF AIR KERMA OF DIAGNOSTIC X-RAY REFERENCE QUALITIES USING A FREE-AIR IONISATION CHAMBER
Authors: Zhao Rui , Wu Jinjie , Wen Yuqin , Lv Yazhu , Guo Bin , Liao Zhenyu
Published: October 2021

Accurate dose measurement is very important for diagnosing X-ray equipment. These equipment should be traced directly or indirectly to primary standard with as little uncertainty as possible. A parallel-plate free-air chamber was designed to measure air kerma of diagnostic X-ray absolutely. Different thickness of aluminium filters were used to obtain different radiation qualities according with IEC 61267. Correction factors were obtained by experiments and simulation, especially the air attenuation factor measured with vacuum method. The relative standard uncertainty of air kerma rate measurement was 0.46% and calibration factor was 0.53%. A transfer ionisation chamber was calibrated with Radiation Qualities in Radiation beams (RQR) qualities in National Research Council of Canada and National Institute of Metrology (NIM), the differences of calibration factors are less than 0.68%.
The limits of motivational influence in ADHD: no evidence for an altered reaction to negative reinforcement
Authors: Van Dessel Jeroen , Sonuga-Barke Edmund J S , Moerkerke Matthijs , Van der Oord Saskia , Morsink Sarah , Lemiere Jurgen , Danckaerts Marina
Published: October 2021

Functional magnetic resonance imaging studies have reported a diminished response in the brain’s reward circuits to contingent cues predicting future monetary gain in adolescents with attention-deficit/hyperactivity disorder (ADHD). The situation with regard to monetary loss is less clear, despite recognition that both positive and negative consequences impact ADHD behaviour. Here, we employ a new Escape Monetary Loss Incentive task in an MRI scanner, which allows the differentiation of contingency and valence effects during loss avoidance, to examine ADHD-related alterations in monetary loss processing. There was no evidence of atypical processing of contingent or non-contingent monetary loss cues in ADHD — either in terms of ratings of emotional and motivational significance or brain responses. This suggests that the ability to process contingencies between performance and negative outcomes is intact in ADHD and that individuals with ADHD are no more (or less) sensitive to negative outcomes than controls. This latter finding stands in stark contrast to recent evidence from a similar task of atypical emotion network recruitment (e.g. amygdala) in ADHD individuals to cues predicting another negative event, the imposition of delay, suggesting marked specificity in the way they respond to negative events.
How Internal Hiring Affects Occupational Stratification
Authors: Wilmers Nathan , Kimball William
Published: October 2021

When employers conduct more internal hiring, does this facilitate upward mobility for low-paid workers or does it protect the already advantaged? To assess the effect of within-employer job mobility on occupational stratification, we develop a framework that accounts for inequality in both rates and payoffs of job changing. Internal hiring facilitates advancement for workers without strong credentials, but it excludes workers at employers with few good jobs to advance into. Analyzing Current Population Survey data, we find that when internal hiring increases in a local labor market, it facilitates upward mobility less than when external hiring increases. When workers in low-paid occupations switch jobs, they benefit more from switching employers than from moving jobs within the same employer. One-third of this difference is due to low-paid workers isolated in industries with few high-paying jobs to transfer into. An occupationally segregated labor market therefore limits the benefits that internal hiring can bring to the workers who most need upward mobility.
The Effect of Split Sentences on Employment and Future Criminal Justice Involvement: Evidence from a Natural Experiment
Authors: Menefee Michael R , Harding David J , Nguyen Anh P , Morenoff Jeffrey D , Bushway Shawn D
Published: October 2021

Jails serve as the front doors of carceral systems, with 10 million jail admissions annually. The people admitted to jail often end up with probation sentences. As a result, there are approximately 3.5 million people on probation supervision in the United States. Despite the widespread reach of these institutions, little sociological research exists on the collateral consequences of jail and probation supervision. We focus on these two forms of criminal justice supervision by examining the use of split sentences, an understudied yet common type of criminal sanction that combines a period of jail incarceration with an ordinary probation sentence. Using rich administrative data, we leverage a natural experiment that relies upon the random assignment of judges to felony cases to estimate causal effects of receiving a split sentence compared to receiving a probation-only sentence. Our identification strategy allows us to isolate the effect of receiving a split sentence among people also sentenced to probation. Our results show that split sentences increase the risk of future prison admissions and, among whites with presentence employment, decrease formal labor market employment. We find that most of the effect of a split sentence on new prison admissions is driven by greater risk of technical violations of probation conditions stemming from higher levels of probation supervision, suggesting that intensification of criminal justice involvement is a self-fulfilling prophecy initiated by the judge’s decision to start a probation sentence with a local jail term.
Payroll-Exempt Labor Incomes Increase Inequality at the Top
Authors: Haupt Andreas , Nollmann Gerd
Published: October 2021

In recent decades, the inequality of household income has increased globally. A common trend is increased income inequality at the top of the distribution. The sources of this trend are a matter of debate. Increased demand for analytical and managerial skills is said to have strongly increased labor incomes at the top. Other scholars have indicated that structural conditions, such as financialization or favorable taxation, have benefited top-earning households. Here, we contribute to the latter line of reasoning. We show that payroll taxes exempt parts of high labor incomes, reinforcing income inequality at the top. Such taxation has large fiscal volume and redistributive power. However, our knowledge about the distributional consequences of payroll taxation as a tax scheme is remarkably thin. Many countries, such as Germany and the United States, restrict payroll taxes to a maximum amount, resulting in significant payroll tax–exempted incomes for high-earning households. Strongly growing top-labor incomes thus lead to increased payroll tax–exempted incomes for households at the upper parts of the distribution and, consequently, to higher income inequality. We use Germany (1992–2017), a highly redistributive country, as a case study. Our empirical results suggest that: (1) households increasingly profit from payroll-exempted labor incomes across the upper quarter; (2) this benefit has increased over time; and (3) increased amounts of payroll tax–exempted labor income explain up to 60 percent of income dispersion at the top of the distribution. We discuss the generalizability of our case study for other countries, especially the United States.
Metabolic perturbations in systemic sclerosis
Authors: O’Reilly Steven
Published: October 2021

Purpose of review

The aim of this review is to evaluate the recent evidence of the role of metabolism in systemic sclerosis (SSc), highlighting specific aberrations and to appraise the feasibility of targeting these therapeutically.

Recent findings

SSc is an autoimmune disease that is characterised by three facets: vascular problems, inflammation, and fibrosis. The fibrosis primarily affects the skin and lungs and currently, no antifibrotic treatment has been found effective. In recent years a renaissance in metabolism research has begun with renewed vigour in the role of metabolism in disease, particularly in the immune system. Alterations in glycolysis and utilisation of specific metabolic pathways in specific cell types have been associated with specific diseases. Most recently alterations in glycolysis and glutaminolysis have been determined in SSc fibroblasts mediating fibrosis. Reduced nicotinamide adenine dinucleotide levels have also been described in SSc.

Specific metabolic aberrations have been described in SSc and this may lead to novel therapeutic targets in this disease.
Artificial intelligence: opportunities in lung cancer
Authors: Zhang Kai , Chen Kezhong
Published: October 2021

Purpose of review

In this article, we focus on the role of artificial intelligence in the management of lung cancer. We summarized commonly used algorithms, current applications and challenges of artificial intelligence in lung cancer.

Recent findings

Feature engineering for tabular data and computer vision for image data are commonly used algorithms in lung cancer research. Furthermore, the use of artificial intelligence in lung cancer has extended to the entire clinical pathway including screening, diagnosis and treatment. Lung cancer screening mainly focuses on two aspects: identifying high-risk populations and the automatic detection of lung nodules. Artificial intelligence diagnosis of lung cancer covers imaging diagnosis, pathological diagnosis and genetic diagnosis. The artificial intelligence clinical decision-support system is the main application of artificial intelligence in lung cancer treatment. Currently, the challenges of artificial intelligence applications in lung cancer mainly focus on the interpretability of artificial intelligence models and limited annotated datasets; and recent advances in explainable machine learning, transfer learning and federated learning might solve these problems.

Artificial intelligence shows great potential in many aspects of the management of lung cancer, especially in screening and diagnosis. Future studies on interpretability and privacy are needed for further application of artificial intelligence in lung cancer.
Oestrogen component of COCs: have we finally found a replacement for ethinyl estradiol?
Authors: Voedisch Amy J. , Fok Wing Kay
Published: October 2021

Purpose of review

Combined oral contraceptive pills are among the most widely used contraceptive methods globally. Despite their popularity, the potential risks and side effects can lead to both high discontinuation rates and adverse outcomes including thromboembolic events. The quest for a safer alternative to the traditional ethinyl estradiol/progestin combination has led to the use of newer oestrogens. Ethinyl oestradiol alternatives will be reviewed including the newest option, estetrol, as it enters clinical use.

Recent findings

Oestradiol, when combined with a progestin with strong endometrial activity, is a viable alternative to ethinyl estradiol in the form of oestradiol valerate and estradiol, which have been available since 2008 and 2011, respectively. Estetrol is the newest oestrogen available and is found naturally in the foetal liver. Estetrol was approved for use in 2021. All three of these alternatives have high contraceptive efficacy, similar if not improved cycle control and decreased impact on haemostatic factors as compared to ethinyl estradiol.

Alternatives to ethinyl oestradiol, including the newest option of estetrol, show promise in providing comparable contraceptive efficacy with potentially lower risk of side effects and thromboembolic events.
Fetal alcohol spectrum disorders: current state of diagnosis and treatment
Authors: Gomez Diego A. , Abdul-Rahman Omar A.
Published: October 2021

Purpose of review

The purpose of this review is to describe recent findings on the clinical presentation, pathogenesis, and management of fetal alcohol spectrum disorders (FASDs). Alcohol causes a range of physical, developmental, and cognitive impairments on the developing fetus. Individuals exposed to alcohol prenatally have a wide variability in dysmorphic and neurologic features. Hence, a greater understanding of the mechanisms through which alcohol induces defects in the developing fetus is imperative in developing therapies that prevent alcohol-induced effects.

Recent findings

Current research has focused on leveraging technology to developing tools that can aid in the diagnostic process, defining patterns of neurocognition and neuroimaging specific to FASD, developing neurobehavioral and pharmacologic interventions, and expanding access to care.

FASDs are a common cause of neurodevelopmental impairment in school-age children, and their recognition is essential to provide early interventions in order to optimize the outcome for these individuals when they reach adulthood. Although previously thought to be the result of irreversible neurologic injury from prenatal alcohol exposure, recent evidence points to the benefits of applying principles regarding neuroplasticity in improving the lives for patients and their families.
Larger guts and faster growth in mice selected for high basal metabolic rate
Authors: Sadowska Julita , Gębczyński Andrzej K. , Konarzewski Marek
Published: October 2021

Postnatal growth in birds and mammals is the time of highest vulnerability and relatively high energy demands and therefore shapes the organisms' future outcomes. Several different factors might impose limitations on growth in juveniles, one of them being the efficiency of the digestive process and size of the gastrointestinal tract. We tested the gut size–growth rate relationship using a unique experimental model—mice from a selection experiment designed to produce two lines with divergent levels of basal metabolic rate (BMR): the high BMR (H-BMR) and low BMR (L-BMR) line types. These lines differ with respect to not only BMR, but also correlated traits—internal organ size and food intake. Applying a cross-fostering design and a thermoregulatory burden imposed by shaving the mothers, we demonstrated that the mass of intestine strongly affected the growth rate, with the H-BMR pups having larger intestines and growing faster, and with reduced growth rate of pups of both lines nursed by shaved L-BMR mothers. Our study also provides a functional link between high growth rate of neonates and high BMR of adults, partly reflecting metabolic costs of maintenance of their guts.
Discerning role of a functional arsenic resistance cassette in evolution and adaptation of a rice pathogen
Authors: Kaur Amandeep , Rana Rekha , Saroha Tanu , Patil Prabhu B.
Published: October 2021

Arsenic (As) is highly toxic element to all forms of life and is a major environmental contaminant. Understanding acquisition, detoxification, and adaptation mechanisms in bacteria that are associated with host in arsenic-rich conditions can provide novel insights into dynamics of host-microbe-microenvironment interactions. In the present study, we have investigated an arsenic resistance mechanism acquired during the evolution of a particular lineage in the population ofXanthomonas oryzaepv.oryzae(Xoo), which is a serious plant pathogen infecting rice. Our study revealed the horizontal acquisition of a novel chromosomal 12kbarscassette inXooIXO1088 that confers high resistance to arsenate/arsenite. Thearscassette comprises several genes that constitute an operon induced in the presence of arsenate/arsenite. Transfer of clonedarscassette toXooBXO512 lacking it confers arsenic resistance phenotype. Further, the transcriptional response ofXooIXO1088 under arsenate/arsenite exposure was analyzed using RNA sequencing. Arsenic detoxification and efflux, oxidative stress, iron acquisition/storage, and damage repair are the main cellular responses to arsenic exposure. Our investigation has provided novel insights in to how a pathogenic bacterium is coping with arsenic-rich unique micro-environments like seen in rice growing in submerged water conditions.

Impact statement

Arsenic accumulation in rice is a serious and unique agronomic issue. Arsenic contaminated groundwater used for irrigation purposes is adding to the accumulation of arsenic in rice. Submerged conditions in the paddy fields further induce the prevalence of toxic inorganic arsenic species in the environment. Our genomics and transcriptomics-based study reveals how a rice pathogen is coping with the lethal concentrations of arsenic by acquiring a novel resistance cassette during diversification into lineages. Acquisition of such detoxification mechanisms can provide a selective advantage to the bacterial population in avoiding toxicity or enhancing virulence and to their on-going evolutionary events. While there are numerous studies on plant-pathogen-environment interactions, our study highlights the importance of systematic studies on the role of unique micro-environmental conditions on the evolution of host-adapted pathogens/microbes.
Ondansetron use is associated with lower COVID-19 mortality in a Real-World Data network-based analysis
Authors: Miller Gregory M. , Ellis J. Austin , Sarangarajan Rangaprasad , Parikh Amay , Rodrigues Leonardo O. , Bruce Can , Chand Nischal Mahaveer , Smith Steven R. , Richardson Kris , Vazquez Raymond , Kiebish Michael A. , Haneesh Chandran , Granger Elder , Holtz Judy , Hinkle Jacob , Narain Niven R. , Goodpaster Bret , Smith Jeremy C. , Lupu Daniel S.
Published: October 2021

Objective

The COVID-19 pandemic generated a massive amount of clinical data, which potentially holds yet undiscovered answers related to COVID-19 morbidity, mortality, long term effects, and therapeutic solutions. The objective of this study was to generate insights on COVID-19 mortality-associated factors and identify potential new therapeutic options for COVID-19 patients by employing artificial intelligence analytics on real-world data.

Methods

A Bayesian statistics-based artificial intelligence data analytics tool (bAIcis®) within Interrogative Biology® platform was used for network learning, inference causality and hypothesis generation to analyze 16,277 PCR positive patients from a database of 279,281 inpatients and outpatients tested for SARS-CoV-2 infection by antigen, antibody, or PCR methods during the first pandemic year in Central Florida. This approach generated causal networks that enabled unbiased identification of significant predictors of mortality for specific COVID-19 patient populations. These findings were validated by logistic regression, regression by least absolute shrinkage and selection operator, and bootstrapping.

Results

We found that in the SARS-CoV-2 PCR positive patient cohort, early use of the antiemetic agent ondansetron was associated with increased survival in mechanically ventilated patients.

Conclusions

The results demonstrate how real world COVID-19 focused data analysis using artificial intelligence can generate valid insights that could possibly support clinical decision-making and minimize the future loss of lives and resources.
GEOexplorer: an R/Bioconductor package for gene expression analysis and visualisation
Authors: Hunt Guy P , Henkin Rafael , Smeraldi Fabrizio , Barnes Michael R
Published: October 2021

Background

Over the past three decades there have been numerous molecular biology developments that have led to an explosion in the number of gene expression studies being performed. Many of these gene expression studies publish their data to the public database GEO, making them freely available. By analysing gene expression datasets, researchers can identify genes that are differentially expressed between two groups. This can provide insights that lead to the development of new tests and treatments for diseases. Despite the wide availability of gene expression datasets, analysing them is difficult for several reasons. These reasons include the fact that most methods for performing gene expression analysis require programming proficiency.

Results

We developed the GEOexplorer software package to overcome several of the difficulties in performing gene expression analysis. GEOexplorer was therefore developed as a web application, that can perform interactive and reproducible microarray gene expression analysis, while producing a wealth of interactive visualisations to facilitate result exploration. GEOexplorer is implemented in R using the Shiny framework and is fully integrated with the existing core structures of the Bioconductor project. Users can perform the essential steps of exploratory data analysis and differential gene expression analysis intuitively and generate a broad spectrum of publication ready outputs.

Conclusion

GEOexplorer is distributed as an R package in the Bioconductor project (http://bioconductor.org/packages/GEOexplorer/). GEOexplorer provides a solution for performing interactive and reproducible analyses of microarray gene expression data, empowering life scientists to perform exploratory data analysis and differential gene expression analysis on GEO microarray datasets.
Genome-edited zebrafish model of ABCC8 loss-of-function disease
Authors: Ikle Jennifer M. , Tryon Robert C. , Singareddy Soma S. , York Nathaniel W. , Remedi Maria S. , Nichols Colin G.
Published: October 2021

KATP channel gain- (GOF) and loss-of-function (LOF) mutations in SUR1 or Kir6.2 underlie human neonatal diabetes mellitus (NDM) and congenital hyperinsulinism (CHI), respectively. Genetically modified mice with transgenic overexpression of GOF mutations recapitulate many features of human NDM and transgenic mice expressing incomplete KATP LOF do reiterate mild hyperinsulinism, although complete KATP knockout mice do not exhibit persistent hyperinsulinism. We have shown that islet excitability and glucose homeostasis in zebrafish are regulated by identical KATP channels to those in mammals, and to explore the possibility of using zebrafish for modeling CHI, we have examined SUR1 truncation mutation (K499X) introduced into the abcc8 gene. Patch-clamp analysis confirmed complete absence of channel activity in β-cells from K499X (SUR1-/-) fish. No difference in random blood glucose was detected in heterozygous SUR1+/- fish, nor in homozygous SUR1-/- fish, mimicking findings in SUR1 knockout mice. Mutant fish also demonstrated impaired glucose tolerance, similar to LOF mouse models. In paralleling features of mammalian hyperinsulinism resulting from loss-of-function mutations, this gene-edited animal provides a valid zebrafish model of KATP LOF driven-dependent pancreatic disease.

Key Points

Loss-of function in the Kir6.2 (KCNJ11) and SUR1 (ABCC8)-encoded pancreatic islet β-cell KATP channels underlie congenital hyperinsulinism. Mouse models reiterate key features, but zebrafish models could provide a powerful model for further analysis and therapy testing.

An early nonsense mutation in exon 10 of SUR1 was generated by ENU mutagenesis.

Patch-clamp analysis revealed an absence of β-cells of SUR1 truncation mutants.

Ca imaging demonstrated elevated basal [Ca]i in β-cells with SUR1 truncation.

Homozygous SUR1 truncation mutants had normal fasting glucose but impaired glucose tolerance as adults, mimicking findings in mouse SUR1 knockouts.

In paralleling features of mammalian diabetes and hyperinsulinism resulting from equivalent loss-of-function mutations, this gene-edited animal provides a valid zebrafish model of KATP -LOF dependent pancreatic diseases.
Brain Data Standards - A method for building data-driven cell-type ontologies
Authors: Tan Shawn Zheng Kai , Kir Huseyin , Aevermann Brian D. , Gillespie Tom , Harris Nomi , Hawrylycz Michael , Jorstad Nik , Lein Ed , Matentzoglu Nicolas , Miller Jeremy A. , Mollenkopf Tyler S. , Mungall Christopher J. , Ray Patrick L. , Sanchez Raymond E. A. , Staats Brian , Vermillion Jim , Yadav Ambika , Zhang Yun , Scheuermann Richard H. , Osumi-Sutherland David
Published: October 2021

Large-scale single-cell ‘omics profiling is revolutionising our understanding of cell types in complex organs like the brain, where it is being used to define a complete catalogue of cell types, something that traditional methods struggle with due to the diversity and complexity of the brain. But this poses a problem. How do we organise such a catalogue - providing a standard way to refer to the cell types discovered, linking their classification and properties to supporting data? Cell ontologies provide a solution to recording definitions, classifications, and properties of cell types and provide standard identifiers for annotation, but they currently do not support the data driven cell type definitions and classifications needed for multi-modal single cell ‘omics profiling.

Here we describe the construction and application of a semi-automated, data-linked extension to the Cell Ontology that represents cell types in the Primary Motor Cortex of humans, mice and marmosets. The methods and resulting ontology are designed to be scalable and applicable to similar whole brain atlases currently in preparation.
Confirmation of fishers’ local ecological knowledge of ciguatoxic fish species and ciguatera-prone hotspot areas in Puerto Rico using harmful benthic algae surveys and fish toxicity testing
Authors: Raab Henry , Luczkovich Joe , Pozo Miguel Del , Griffith David , Grace-McCaskey Cindy , Litaker Wayne
Published: October 2021

Ciguatoxin fish poisoning (CFP) is caused by the consumption of tropical and subtropical fishes and other marine species with high levels of ciguatoxin (CTX) in their tissues. CTX is a polycyclic neurotoxin produced by single-celled, photosynthetic dinoflagellates in the Gambierdiscus and Fukuyoa genera which are found in close association with benthic autotrophs. CTX enters the food web when these dinoflagellates are inadvertently consumed by herbivores grazing on their preferred substrates. The toxin biomagnifies up the food chain to the top predators and if humans consume seafood with high levels of CTX it can cause a variety of flu-like symptoms. The best way to avoid CFP is to avoid toxic fishes. However, CTX is undetectable by physical inspection. This study investigated local fishers’ knowledge of ciguatera hotspots and coldspots along Puerto Rican coral reefs using toxic-dinoflagellate cell counts and by estimating fish toxicity in those sites using a cell-based Neuro-2a cytotoxicity assay. The fishers identified regions of high and low risk for CFP based on their local ecological knowledge (LEK) which were deemed hotspots and coldspots, respectively. There is a 35-fold difference in dinoflagellate cell counts of low-toxicity Gambierdiscus species in samples in the identified hotspot compared to the coldspot. Also, higher trophic level fishes (>3.4 ETL) had higher median estimates of CTX in their tissues at the hotspot than the same species in the coldspot. This study shows the effectiveness of LEK in identifying potential problem areas for ciguatera.
Distinct competitive impacts of palatability of taste stimuli on sampling dynamics during a preference test
Authors: Ballintyn Benjamin , Ksander John , Katz Donald , Miller Paul
Published: October 2021

Food or taste preference tests are analogous to naturalistic decisions in which the animal selects which stimuli to sample and for how long to sample them. The data acquired in such tests, the relative amounts of the alternative stimuli that are sampled and consumed, indicate the preference for each. While such preferences are typically recorded as a single quantity, an analysis of the ongoing sampling dynamics producing the preference can reveal otherwise hidden aspects of the decision-making process that depend on its underlying neural circuit mechanisms. Here, we perform a dynamic analysis of two factors that give rise to preferences in a two-alternative task, namely the distribution of durations of sampling bouts of each stimulus and the likelihood of returning to the same stimulus or switching to the alternative—i. e., the transition probability—following each bout. The results of our analysis support a specific computational model of decision-making whereby an exponential distribution of bout durations has a mean that is positively correlated with the palatability of that stimulus, but also negatively correlated with the palatability of the alternative. This impact of the alternative stimulus on the distribution of bout durations decays over a timescale of tens of seconds, even though the memory of the alternative stimulus lasts far longer—long enough to impact the transition probabilities upon ending bouts. Together, our findings support a state-transition model for bout durations and suggest a separate memory mechanism for stimulus-selection.