bluuebunny/crossref_metadata_2025 huggingface dataset:
Irrigation and Rootstocks to Manage Northern Root-Knot Nematode During Wine Grape Vineyard Establishment
Authors: East Katherine E. , Zasada Inga A. , Schreiner R. Paul , Moyer Michelle M.
Published: September 2021

Vineyard replanting in Washington state can be negatively impacted by the plant-parasitic nematode Meloidogyne hapla. Chemically focused nematode management programs do not offer long-term suppression; however, this may be achieved through the adoption of cultural approaches such as rootstocks and irrigation. Nematode-resistant rootstocks are used extensively in other regions but many have not been tested against M. hapla. Vineyards in eastern Washington are irrigated; therefore, manipulating available soil water may also impact nematode development. In 2017, two field trials were established in eastern Washington to evaluate the effects of (i) late-summer water limitation on M. hapla population development and (ii) host status of 1103 Paulsen, 3309 Couderc, and Matador rootstocks for M. hapla. The efficacy of these cultural management approaches was evaluated under three initial M. hapla densities (0, 50, and 250 M. hapla second-stage juveniles per 250 g of soil) in both trials. Reducing irrigation to manage M. hapla infestation of grape roots was ineffective and may cause harm to the vines by inducing too much water stress. Conversely, rootstocks effectively reduced population densities of M. hapla. Overall, rootstocks show the most promise as a cultural tool to manage M. hapla during the establishment phase in Washington vineyards.
Screening for hypertrophic cardiomyopathy
Authors: Pydah Sunayana C. , Mauck Kimberlee , Shultis Chelsea , Rolfs Jenna , Schmidt Eric , Nicholas Joyce
Published: September 2021

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy and causes changes in the cardiac muscle affecting ventricular, valvular, and cellular functions. Because HCM is an inherited disorder, all age groups are affected; however, it commonly presents in adolescents, especially athletes. Many patients are asymptomatic and undiagnosed, putting them at risk for sudden cardiac death. This article describes screening and management of patients with HCM.
Primary care workforce paradox
Authors: White Ryan , Keahey David , Luck Morgan , Dehn Richard W.
Published: September 2021

Objective:

Primary care workforce projections continue to predict significant physician shortages. An oversupply of primary care physician assistants (PAs) and NPs also is predicted. This paradox calls into question the assumptions that underlie workforce projection models, which likely underestimate the primary care contributions of PAs and NPs.

Methods:

Federally qualified health center data from the 2016-2019 Uniform Data System were used to calculate the number of clinic visits per full-time equivalent (FTE) physician, PA, and NP. Visits per FTE were compared across provider type to determine provider-specific productivity ratios.

Results:

The combined PA and NP productivity ratio increased relative to physicians in each year, ranging from 0.85 in 2016 to 0.88 in 2019. Clinic visits per FTE for PAs and family physicians were nearly equivalent.

Conclusions:

Primary care workforce projection models should be reexamined to more accurately capture the productivity of PAs and NPs.
Attentional interference by pain in a dishabituation procedure: an experimental investigation
Authors: De Paepe Annick L. , Crombez Geert
Published: September 2021

The ability to habituate to pain may be adaptive, and it may enable us to pursue valuable goals despite the pain. In this study, we experimentally investigated this idea using the primary task paradigm in which participants had to identify the color of a circle (blue or yellow) as quickly as possible while ignoring painful or tactile distractors that are presented on some of the trials. In the first experiment, we were interested whether the attentional interference effect because of the presentation of the distractors and its habituation would differ between painful and tactile distractor stimuli. In the second experiment, we investigated dishabituation (ie, the phenomenon that the introduction of a different stimulus results in an increase of the decremented response to the original stimulus). We expected habituation of the attentional interference to occur both in the tactile and the painful distractor condition, but to be less complete in the painful condition. Moreover, we hypothesized that the dishabituation would be stronger for the painful than for the tactile distractors. We did find evidence for an interference effect because of the presence of distractors. We also found habituation of attentional interference. However, the interference and its habituation were no different for tactile and painful distractors. Moreover, we did not find evidence for dishabituation. These are the first studies of their kind. Implications and guidelines for future research are formulated.
The “CIV Classification,” a New Proposal for the Architectural Grading of Vulvar Lichen Sclerosus
Authors: Boero Veronica , Liverani Carlo A. , Brambilla Massimiliano , Monti Ermelinda , Tozzi Roberto , Murina Filippo , Di Loreto Eugenia , Cipriani Sonia , Libutti Giada , Cetera Giulia E. , Iorio Maria , Dell'Acqua Andrea , Parazzini Fabio
Published: September 2021

Objectives

The purpose of this cross-sectional study was to prepare a reliable and easy-to-use architectural classification for vulvar lichen sclerosus (VLS) aimed at defining the morphological patterns of this condition.

Materials and Methods

An expert panel composed by 7 physicians with expertise in clinical care of vulvar conditions outlined the architectural criteria for the definition of VLS severity (phimosis of the clitoris, involvement of the interlabial sulci, narrowing of the vulvar introitus), identifying 5 grades to build up a classification. Thirteen physicians with 2–30 years expertise in vulvar diseases (nonexpert group) were asked to evaluate 3–5 pictures from 137 patients. Each physician individually assigned a grade to each case, according to the previously mentioned criteria. Interrater reliability was analyzed by means of intraclass correlation coefficient (ICC). The reliability concerning the 2 classifications of each rater was analyzed by means of κ statistic. Intraobserver and interobserver reliability in vivo was analyzed by means of κ index.

Results

This study provides a new classification of VLS, based on defined anatomical criteria and graded into mutually exclusive progressive classes.

The ICC analysis showed a substantial interrater reliability of the classification, ICC = 0.89 (0.87–0.91), both in the expert panel and in the nonexpert group (ICC = 0.92 and 0.87, respectively). An “almost perfect” intraobserver and interobserver reliability was achieved among physicians in vivo (κ = 0.93).

Conclusions

Our classification showed a high reliability. It is easy to use, and it can be applied in clinical practice and eventually, in the evaluation of regenerative and cosmetic surgery.
Nursing Moral Distress and Intent to Leave Employment During the COVID-19 Pandemic
Authors: Sheppard Katherine N. , Runk Barbara G. , Maduro Ralitsa S. , Fancher Monica , Mayo Andrea N. , Wilmoth Donna D. , Morgan Merri K. , Zimbro Kathie S.
Published: September 2021

Background:

Complexity in nursing practice creates an intense and stressful environment that may lead to moral distress (MD) and registered nurses (RNs) seeking other employment.

Local Problem:

In 2020, the RN turnover rate was 8%, with postpandemic turnover projected to reach 13%.

Methods:

The Measure of Moral Distress for Health Care Professionals (MMD-HP) was used to measure the frequency and level of RNs' MD.

Results:

t tests showed significant differences for 16 of 27 MMD-HP items in RN intent to leave. RNs had 2.9 times the odds of intent to leave (P = .019) due to perceived issues with patient quality and safety and 9.1 times the odds of intent to leave (P < .001) due to perceived issues with the work environment. Results explained 40.3% of outcome variance.

Conclusions:

MD related to work environment or patient quality and safety were significant factors in RN intent to leave their position.
Fundamental Pharmacokinetic Concepts and Their Clinical Relevance: Clearance, Zero Versus First Order and Nonlinear Pharmacokinetics
Authors: Preskorn Sheldon H.
Published: September 2021

In response to a question posed by a valued colleague, this column will discuss 4 fundamental pharmacokinetic concepts: (1) What does the term clearance encompass? (2) What do the terms first order and second order pharmacokinetics mean? (3) What does the term nonlinear pharmacokinetics mean and is it just a synonym for zero order pharmacokinetics? (4) What is the clinical relevance, if any, of these concepts and why? In addition, this column cites several earlier columns that are relevant to aspects of each of the answers. Thus, readers interested in more details can refer to these earlier publications that include case examples and figures that further illustrate various points. In considering the clinical relevance of these pharmacokinetic concepts, this column discusses relative binding affinity for targets and the concept of selective versus nonselective drugs, which are foundational cornerstones for understanding and optimally using currently available psychopharmaceutical agents.
Predicting 30-Day Readmissions: Evidence From a Small Rural Psychiatric Hospital
Authors: Daley Angela , Scobie Brent , Shorey Jason , Breece James , Oxley Scott
Published: September 2021

To improve quality of care and patient outcomes, and to reduce costs, hospitals in the United States are trying to mitigate readmissions that are potentially avoidable. By identifying high-risk patients, hospitals may be able to proactively adapt treatment and discharge planning to reduce the likelihood of readmission. Our objective in this study was to derive and validate a predictive model of 30-day readmissions for a small rural psychiatric hospital in the northeast. However, this model can be adapted by other rural psychiatric hospitals—a context that has been understudied in the literature. Our sample consisted of 1912 adult inpatients (1281 in the derivation cohort and 631 in the validation cohort), who were admitted between August 1, 2014, and July 31, 2016. We used deidentified data from the hospital’s electronic medical record, including physician orders and discharge summaries. These data were merged with community-level variables that reflected the availability of care in the patients’ zip codes. We first considered the correlates of 30-day readmission in a regression framework. We found that the probability of readmission increased with the number of previous admissions (vs. no readmissions). Moreover, the probability of readmission was much higher for patients with a depressive disorder (vs. no depressive disorder), with another mood disorder (vs. no other mood disorder), and/or with a psychotic disorder (vs. no psychotic disorder). We used these associations to derive a predictive model, in which we used the regression coefficients to construct a score for each patient. We then estimated the predicted probability of 30-day readmission on the basis of that score. After validating the model, we discuss the implications for clinical practice and the limitations of our approach.
Improvement in Memory Deficits With Memantine in Mania Secondary to Traumatic Brain Injury and Preexisting Perinatal Birth Injury
Authors: Das Aparna , Brasseux Stephen
Published: September 2021

Cognitive deficits are known to occur after brain injury, be it perinatal injury, traumatic brain injury (TBI), or any other type of insult to the brain. The problem may be compounded if psychiatric illness is present in addition to the brain injury because the illness itself or the psychotropic medications used in its management may lead to worsening of cognitive functioning. We present the case of a patient who presented to the hospital with symptoms suggestive of mania with psychotic features that had started after a recent TBI, with the brain scan also revealing the presence of a preexisting perinatal birth injury. When the patient recovered from the psychiatric symptoms, he still appeared to have memory problems that improved with the use of add-on memantine, an N-methyl-D-aspartate receptor antagonist. To date, there is some literature supporting the off-label use of memantine as a cognitive enhancer in patients with TBIs and other psychiatric illnesses, such as bipolar disorder.
Anatomy behind the Paramedian Platysmal Band: A Combined Cadaveric and Computed Tomographic Study
Authors: Davidovic Kristina , Frank Konstantin , Schenck Thilo L. , Cohen Steven R. , Dayan Steven , Gotkin Robert H. , Sykes Jonathan M. , Liew Steven , Gavril Diana , Cotofana Sebastian
Published: September 2021

Background:

The muscular hypothesis explanation of the pathophysiology behind paramedian platysmal bands does not seem to provide a sufficient explanation for the clinical presentation of these platysmal bands in aged individuals with cervical soft-tissue laxity. The purpose of this study was to investigate the fascial relationships of the anterior neck to enhance appropriate surgical treatment.

Methods:

Retrospective analysis of computed tomographic scans of 50 Caucasian individuals (mean age, 55.84 ± 17.5 years) and anatomical dissections of 20 Caucasian and 10 Asian body donors (mean age, 75.88 ± 10.6 years) were conducted. Fascial adhesions were classified according to platysma fusion types, and platysma mobility was tested during dissection procedures.

Results:

Fusion between the left and right platysma muscles occurred in 64 percent in the suprahyoid region and in 20 percent at the thyroid cartilage, and in 16 percent, the platysma attached to the mandible without fusion. In the absence of muscular fibers, a fascial adhesion zone with limited mobility was observed where the superficial cervical fascia fused with the investing layer of the deep cervical fascia.

Conclusions:

Muscular contraction of the platysma results in elevation of the most medial platysma muscle fibers, which are not attached in the fascial adhesion zone. The presence of a fatty layer deep to the platysma enables platysmal movement and anterior and inferior gliding of the skin and platysma when cervical soft-tissue laxity exists. Surgical treatments should include transection of the fascial adhesion; this could potentially prevent the recurrence of paramedian platysmal bands.
Osseous Genioplasty: Prevention of Witch’s Chin Deformity with No-Degloving Technique
Authors: Zhang Ben H. , Byrd Rosemarie , Bradley Conor , Volpicelli Elizabeth J. , Gibstein Alexander R. , Fisher Mark , Lee Justine C. , Bradley James P.
Published: September 2021

Background:

Osseous genioplasty is a powerful procedure that can correct chin dysmorphology; however, traditional techniques may result in chin ptosis or a “witch’s chin” deformity. Iatrogenic chin ptosis is thought to be caused by excessive degloving of soft tissue with a failure to reattach the mentalis muscle. In the authors’ study, they compared the “no-degloving” technique (using a 90-degree plate with lag-screw fixation) to the “traditional” technique, for minimization of chin ptosis.

Methods:

The authors compared genioplasty techniques for consecutive patients: group 1 (traditional) underwent degloving for fixation of a stair-step plate, whereas group 2 (no-degloving) underwent lag-screw fixation (n = 50; 25 patients per group). The authors compared operating room time, advancement, complications, preoperative-to-postoperative vertical height change of the pogonion and menton (obtained through cone beam computed tomographic scans), surgeons’ assessment of witch’s chin, and FACE-Q surveys.

Results:

No-degloving versus traditional groups had similar age and sex distributions, horizontal/vertical change (5 mm/2 mm versus 6 mm/2 mm), length of surgery, and complication rate (5 percent). The traditional group had more deviation from expected position for both the pogonion (3.4 mm versus 1.2 mm; p ≤ 0.05) and menton (2.9 mm versus 0.8 mm; p ≤ 0.05), and more occurrences of witch’s chin (six versus zero). No-degloving was superior for several FACE-Q scales, including Chin Appearance, Quality of Life, Satisfaction with Decision to Undergo Procedure, and Satisfaction with Outcome.

Conclusion:

No-degloving osseous genioplasty is a safe, reproducible technique that results in decreased soft-tissue ptosis and increased patient satisfaction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Racial disparities in triage of adolescent patients after bullet injury
Authors: Andrade Erin G. , Onufer Emily J. , Thornton Melissa , Keller Martin S. , Schuerer Douglas J.E. , Punch LJ
Published: September 2021

BACKGROUND

While pediatric trauma centers (PTCs) and adult trauma centers (ATCs) exhibit equivalent trauma mortality, the optimal care environment for traumatically injured adolescents remains controversial. Race has been shown to effect triage within emergency departments (EDs) with people of color receiving lower acuity triage scores. We hypothesized that African-American adolescents were more likely triaged to an ATC than a PTC compared with their White peers.

METHODS

Institutional trauma databases from a neighboring, urban Level I PTC and ATC were queried for gunshot wounds in adolescents (15–18 years) presenting to the ED from 2015 to 2017. The PTC and ATC were compared in terms of demographics, services, and outcomes. Results were analyzed using univariate analysis and logistic regression.

RESULTS

Among 316 included adolescents, 184 were treated in an ATC versus 132 in a PTC. Patients at the PTC were significantly more likely to be younger (16.1 vs. 17.5 years; p < 0.001), White (16% vs. 5%; p = 0.001), and privately insured (41% vs. 30%; p = 0.002). At each age, the proportion of Whites treated at the PTC exceeded the proportion of African-Americans. At the PTC, patients were more likely to receive inpatient and outpatient social work follow-up (89% vs. 1%, p < 0.001). Adolescents treated at the PTC were less likely to receive opioids (75% vs. 56%, p = 0.001) at discharge and to return to ED within 6 months (25% vs. 11%, p = 0.005). On multivariate logistic regression, African-American adolescents were less likely to be treated at a PTC (odds ratio, 0.30; 95% confidence interval, 0.10–0.85; p = 0.02) after controlling for age and Injury Severity Score.

CONCLUSION

Disparities in triage of African-American and White adolescents after bullet injury lead to unequal care. African-Americans were more likely to be treated at the ATC, which was associated with increased opioid prescription, decreased social work support, and increased return to ED.

LEVEL OF EVIDENCE

Therapeutic/Care Management, Level IV.
Observational management of penetrating occult pneumothoraces: Outcomes and risk factors for interval tube thoracostomy placement
Authors: Beattie Genna , Cohan Caitlin M. , Tang Annie , Chen Joshua Y. , Victorino Gregory P.
Published: September 2021

BACKGROUND

Guidelines for penetrating occult pneumothoraces (OPTXs) are based on blunt injury. Further understanding of penetrating OPTX pathophysiology is needed. In observational management of penetrating OPTX, we hypothesized that specific clinical and radiographic features may be associated with interval tube thoracostomy (TT) placement. Our aims were to (1) describe OPTX occurrence in penetrating chest injury, (2) determine the rate of interval TT placement in observational management and clinical outcomes compared with immediate TT placement, and (3) describe risk factors associated with failure of observational management.

METHODS

Penetrating OPTX patients presenting to our level 1 trauma center from 2004 to 2019 were reviewed. Occult pneumothorax was defined as a pneumothorax on chest computed tomography but not on chest radiograph. Patient groups included immediate TT placement versus observation. Clinical outcomes compared were TT duration and complications, need for additional thoracic procedures, length of stay (LOS), and disposition. Clinical and radiographic factors associated with interval TT placement were determined by multivariable regression.

RESULTS

Of 629 penetrating pneumothorax patients, 103 (16%) presented with OPTX. Thirty-eight patients underwent immediate TT placement, and 65 were observed. Twelve observed patients (18%) needed interval TT placement. Regardless of initial management strategy, TT placement was associated with longer LOS and more chest radiographs. Chest injury complications and outcomes were similar. Factors associated with increased odds of interval TT placement included Chest Abbreviated Injury Scale score of ≥4 (adjusted odds ratio [aOR], 7.38 [95% confidence interval, 1.43–37.95), positive pressure ventilation (aOR, 7.74 [1.07–56.06]), concurrent hemothorax (aOR, 6.17 [1.08–35.24]), and retained bullet fragment (aOR, 11.62 [1.40–96.62]) (all p < 0.05).

CONCLUSION

The majority of patients with penetrating OPTX can be successfully observed with improved clinical outcomes (LOS, avoidance of TT complications, reduced radiation). Interval TT intervention was not associated with risk for adverse outcomes. In patients undergoing observation, specific clinical factors (chest injury severity, ventilation) and imaging features (hemothorax, retained bullet) are associated with increased odds for interval TT placement, suggesting need for heightened awareness in these patients.

LEVEL OF EVIDENCE

Prognostic, level IV.
Potential Impacts of Mass Nutritional Supplementation on Measles Dynamics: A Simulation Study
Authors: Noori Navideh , Skrip Laura A. , Oron Assaf P. , McCarthy Kevin A. , Proctor Josh L. , Chabot-Couture Guillaume , Althouse Benjamin M. , Phelan Kevin P.Q. , Trehan Indi
Published: September 2021

The bidirectional interaction between undernutrition and infection can be devastating to child health. Nutritional deficiencies impair immunity and increase susceptibility to infection. Simultaneously, infections compound undernutrition by increasing metabolic demand, and impairing nutrient absorption. Treatment of acute malnutrition (wasting) can reverse some of its deleterious effects and reduce susceptibility to infectious diseases. Nutrition-specific approaches may be packaged with other interventions, including immunization, to support overall child health. To understand how mass nutritional supplementation, treatment of wasting, and vaccination affect the dynamics of a vaccine-preventable infection, we developed a population-level, compartmental model of measles transmission stratified by age and nutrition status. We simulated a range of scenarios to assess the potential reductions in measles infection and mortality associated with targeted therapeutic feeding for children who are wasted and with a mass supplementation intervention. Nutrition interventions were assumed to increase engagement with the health sector, leading to increased vaccination rates. We found that the combination of wasting treatment and mass supplementation coverage followed by an increase in vaccination coverage of non-wasted children from a baseline of 75% to 85%, leads to 34-57% and 65-77% reduction in measles infection and mortality and 56-60% reduction in overall mortality among wasted children, compared with the wasting treatment alone. Our work highlights the synergistic benefits that may be achieved by leveraging mass nutritional supplementation as a touch point with the health system, to increase rates of vaccination and improve child survival beyond what would be expected from the additive benefits of each intervention.
Ultrasound exposure enhances cellular uptake of nanoscale cargos
Authors: Bansal Kahkashan , Rajwar Anjali , Shekhar Himanshu , Bhatia Dhiraj
Published: September 2021

DNA nanotechnology utilizes DNA as a structural molecule to design palette of nanostructures with different shapes and sizes. DNA nanocages have demonstrated significant potential for drug delivery. Therefore, enhancing the delivery of DNA nanocages into cells can improve their efficacy as drug delivery agents. Numerous studies have reported the effects of ultrasound for enhancing drug delivery across biological barriers. The mechanical bioeffects caused by cell-ultrasound interaction can cause sonoporation, leading to enhanced uptake of drugs, nanoparticles, and chemotherapeutic agents through membranes. Whether ultrasound exposure can enhance the delivery of DNA nanocages has not been explored, which is the focus of this study. Specifically, we investigated the effects of ultrasound on the cellular uptake of propidium Iodide, fluorescent dextrans, and DNA nanostructures). We provide evidence of modulation of pore formation in the cell membrane by ultrasound by studying the intracellular uptake of the impermeable dye, propidium iodide. Treatment of cells with low amplitudes of ultrasound enhanced the uptake of different sizes of dextrans and DNA based nanodevices. These findings could serve as the foundation for further development ultrasound-enabled DNA nanostructure delivery and for specific understanding of underlying biological mechanisms of interaction between ultrasound parameters and cellular components; the knowledge that can be further explored for potential biological and biomedical applications.
DeepREAL: A Deep Learning Powered Multi-scale Modeling Framework Towards Predicting Out-of-distribution Receptor Activity of Ligand Binding
Authors: Cai Tian , Abbu Kyra Alyssa , Liu Yang , Xie Lei
Published: September 2021

Drug discovery has witnessed intensive exploration of the problem of drug-target physical interactions over two decades, however, a strong drug binding affinity to a single target often fails to translate into desired clinical outcomes. A critical knowledge gap needs to be filled for correlating drug-target interactions with phenotypic responses: predicting the receptor activities or function selectivity upon the ligand binding (i.e., agonist vs. antagonist) on a genome-scale and for novel chemicals. Two major obstacles compound the difficulty on this direction: known data of receptor activity is far too scarce to train a robust model in light of genome-scale applications, and real-world applications need to deploy a model on data from various shifted distributions. To address these challenges, we have developed an end-to-end deep learning framework, DeepREAL, for multi-scale modeling of genome-wide receptor activities of ligand binding. DeepREAL utilizes self-supervised learning on tens of millions of protein sequences and pre-trained binary interaction classification to solve the data distribution shift and data scarcity problems. Extensive benchmark studies that simulate real-world scenarios demonstrate that DeepREAL achieves state-of-the-art performance in out-of-distribution settings.
Morphological alternations of intracerebral arterial during middle age: a community cohort study
Authors: Zhang Boyu , Yang Zidong , Li Jing , Wang Bei , Shi Huazheng , Wang He , Li Yuehua
Published: September 2021

Background

Ample evidence has suggested that vascular modifications are associated with aging. To expand previous understanding of age-related vascular changes, we examined the association between aging and cerebrovascular morphologies.

Methods

1176 participants aged 35 to 75 years recruited from Shanghai, China were included in this study. Cerebrovascular morphological features comprising arterial branch density, radius, and tortuosity were quantified using three-dimensional magnetic resonance angiography. Linear regression was used to examine the association between age and vasculature features.

Results

Age was found to be a significant predictor for cerebrovascular morphological alterations after adjusting for vascular risk factors. However, after dividing subjects into subgroups based on their age, aging was found to be significantly correlated with all three morphometric features only in the 45-54 subgroup after adjusting for the other vascular risk factors. Smoking gives rise to a more rapid age-related changes in vascular morphologies, while alcohol consumption could decelerate those age-related alterations.

Conclusions

Rapid alternations in all three morphological features assessed have been noticed to be associated with aging in the 45-54 subgroup, suggesting the potential importance of the 5th decade for early preservation method of vascular aging.

Funding

National Natural Science Foundation of China.
Using Artificial Intelligence-based models to predict the risk of Mucormycosis among COVID-19 Survivors: An Experience from India
Authors: Syed-Abdul Shabbir , Babu A. Shoban , Bellamkonda Raja Shekhar , Itumalla Ramaiah , Acharyulu GVRK , Krishnamurthy Surya , Santosh Ramana Y. Venkat , Mogilicharla Naresh , Malwade Shwetambara , (Jack) Li Yu-Chuan
Published: September 2021

Introduction

India reported a severe public health challenge not only due to the COVID-19 outbreak but also the increasing number of associated mucormycosis cases since 2021. This study aimed at developing artificial intelligence-based models to predict the risk of mucormycosis among the patients at the time of discharge from the hospital.

Methods

The dataset included 1229 COVID-19 positive patients, and additional 214 inpatients, COVID-19 positive as well as infected with mucormycosis. We used logistic regression, decision tree, and random forest, and the extreme gradient boosting algorithm. All our models were evaluated with 5-fold validation to derive a reliable estimate of the model error.

Results

The logistic regression, XGBoost, and random forest performed equally well with AUROC 95.0, 94.0, and 94.0 respectively. This study also determined the top five variables namely obesity, anosmia, de novo diabetes, myalgia, and nasal discharge, which showed a positive impact on the risk of mucormycosis.

Conclusion

The developed model has the potential to predict the patients at high risk and thus, consequently initiating preventive care or aiding in early detection of mucormycosis infection. Thus, this study holds potential for early treatment and better management of patients suffering from COVID-19 associated mucormycosis.
Impaired KDM2B-mediated PRC1 recruitment to chromatin causes neural stem cell senescence and ASD/ID-like behavioral deficits
Authors: Gao Yuen , Duque-Wilckens Natalia , Aljazi Mohammad B , Moeser Adam J , Mias George I , Robison Alfred J , Zhang Yi , He Jin
Published: September 2021

Autism spectrum disorder (ASD) and intellectual disability (ID) are neurodevelopmental diseases associated with various genetic mutations. Recent clinical studies report that chromosomal 12q24.31 microdeletions are associated with human ASD/ID. However, the causality and underlying mechanisms linking 12q24.31 microdeletions to ASD/ID pathogenesis remain undetermined. Here we show Kdm2b, one of the genes located in chromosomal 12q24.31, plays a critical role in maintaining neural stem cells (NSCs) in the developing mouse brain. Loss of the CxxC-ZF domain of KDM2B impairs its function in recruiting Polycomb repressive complex 1 (PRC1) to chromatin, resulting in de-repression of genes involved in cell apoptosis, cell cycle arrest, NSC premature senescence, and leading to the loss of NSC populations in the brain. Importantly, the Kdm2b mutation is sufficient to induce ASD/ID-like social and memory deficits in adult mice. Thus, our study reveals a critical role of an epigenetic factor KDM2B in normal brain development, a causality between the Kdm2b mutation and genesis of ASD/ID-like phenotypes in mice, and potential molecular mechanisms linking the function of KDM2B-PRC1 in transcriptional regulation and NSC senescence to the12q24.31 microdeletion-associated ASD/ID.
Morphometric Analysis of Lungfish Endocasts Elucidates Early Dipnoan Palaeoneurological Evolution
Authors: Clement Alice M. , Challands T. J. , Cloutier Richard , Houle Laurent , Ahlberg Per E. , Collin Shaun P. , Long John A.
Published: September 2021

Lungfish (Dipnoi) are lobe-finned fish (Sarcopterygii) that have persisted for over 400 million years from the Devonian Period to present day. They are the extant sister group to tetrapods and thus have the ability to provide unique insight into the condition of the earliest tetrapods as well as their own evolutionary history. The evolution of their dermal skull and dentition is relatively well understood, but this is not the case for the central nervous system. While the brain itself has very poor preservation potential and is not currently known in any fossil lungfish, substantial indirect information about it and associated structures such as the inner ears can be obtained from the cranial endocast. However, before the recent development of X-ray tomography as a palaeontological tool, these endocasts could not be studied non-destructively, and few detailed studies were undertaken. Here we describe and illustrate the endocasts of six Palaeozoic lungfishes (Iowadipterus halli, Gogodipterus paddyensis, Pillararhynchus longi, Griphognathus whitei, Orlovichthys limnatis, andRhinodipterus ulrichi) from tomographic scans. We combine these with six previously described lungfish endocasts (4 fossil and 2 recent taxa), also based on tomographic studies, into a 12-taxon data set for multivariate morphometric analysis using 17 variables. We find that the olfactory region appears to be more highly plastic than the hindbrain, and undergoes significant elongation in several taxa. Further, while the semicircular canals covary as an integrated module, the utriculus and sacculus of the inner ear instead vary independently of each other. The functional and phylogenetic implications of our findings are discussed.
A model of preferential pairing between epithelial and dendritic cells in thymic antigen transfer
Authors: Vobořil Matouš , Březina Jiří , Brabec Tomáš , Dobeš Jan , Ballek Ondřej , Dobešová Martina , Manning Jasper , Blumberg Richard S. , Filipp Dominik
Published: September 2021

Medullary thymic epithelial cells (mTECs) which produce and present self-antigens are essential for the establishment of central tolerance. Since mTEC numbers are limited, their function is complemented by thymic dendritic cells (DCs), which transfer mTEC-produced self-antigens via cooperative antigen transfer (CAT). While CAT is required for effective T cell selection, many aspects remain enigmatic. Given the recently described heterogeneity of mTECs and DCs, it is unclear whether the antigen acquisition from a particular TEC subset is mediated by preferential pairing with specific subset of DCs. Using several relevant Cre-based mouse models controlling the expression of fluorescent proteins, we found that in regards to CAT, each subset of thymic DCs preferentially targets distinct mTEC subset(s) and importantly, XCR1+ activated DCs represented the most potent subset in CAT. Interestingly, one thymic DC can acquire antigen repetitively and of these, monocyte-derived DCs (moDC) were determined to be the most efficient in repetitive CAT. moDCs also represented the most potent DC subset in the acquisition of antigen from other DCs. These findings suggest a preferential pairing model for the distribution of mTEC-derived antigens among distinct populations of thymic DCs.
BioCAT: a novel tool to search biosynthetic gene clusters producing nonribosomal peptides with a known structure
Authors: Konanov D.N. , Krivonos D.V. , Ilina E.N. , Babenko V.V.
Published: September 2021

Motivation

Nonribosomal peptides are a class of secondary metabolites synthesized by multimodular enzymes named nonribosomal peptide synthetases and mainly produced by bacteria and fungi. It has been shown that non-ribosomal peptides have a huge structural and functional diversity including antimicrobial activity, therefore, they are of increasing interest for modern biotechnology. Methods such as NMR and LC-MS/MS allow to determine a peptide structure precisely, but it is often not a trivial task to find natural producers of them. Today, the search is usually performed manually, mostly with tools such as antiSMASH or Prism. However, there are cases when potential producers should be found among hundreds of strains, for instance, when analyzing metagenomes data. Thus, the development of automated approaches is a high-priority task for further nonribosomal peptides research.

Results

We developed BioCAT, a two-side approach to find biosynthetic gene clusters which may produce a given nonribosomal peptide when the structure of interesting nonribosomal peptide has already been found. Formally, BioCAT unites the antiSMASH software and the rBAN retrosynthesis tool but some improvements were added to both gene cluster and peptide chemical structure analyses. The main feature of the method is an implementation of position specific score matrix to store specificities of nonribosomal peptide synthetase modules, which has increased the alignment quality in comparison with more strict approaches developed earlier. An ensemble model was implemented to calculate the final alignment score. We tested the method on a manually curated nonribosomal peptides producers database and compared it with a competing tool called GARLIC. Finally, we showed the method applicability on several external examples.

Availability

BioCAT is available on the GitHub repository or via pip

Contact

konanovdmitriy@gmail.com
Permutational immune analysis reveals architectural similarities between inflammaging, Down syndrome and autoimmunity
Authors: Lambert Katharina , Moo Keagan G. , Arnett Azlann , Goel Gautam , Flynn Kaitlin J. , Speake Cate , Wiedeman Alice E. , Greenbaum Carla J. , Long S. Alice , Partridge Rebecca , Buckner Jane H. , Khor Bernard
Published: September 2021

People with Down syndrome show cellular and clinical features of dysregulated aging of the immune system, including naïve-memory shift in the T cell compartment and increased incidence of autoimmunity. However, a quantitative understanding of how various immune compartments change with age in Down syndrome remains lacking. Here we performed deep immunophenotyping of a cohort of individuals with Down syndrome across the lifespan, selecting for individuals not affected by autoimmunity. We simultaneously interrogated age- and sex-matched healthy neurotypical controls and people with type 1 diabetes, as a representative autoimmune disease. We built a new analytical software, IMPACD, that enabled us to rapidly identify many features of immune dysregulation in Down syndrome that are recapitulated in other autoimmune diseases. We found significant quantitative and qualitative dysregulation of naïve CD4+and CD8+T cells in Down syndrome and identified IL-6 as a candidate driver of some of these changes, thus extending the consideration of immunopathologic cytokines in Down syndrome beyond interferons. Notably, we successfully used immune cellular composition to generate three quantitative models of aging (i.e. immune clocks) trained on control subjects. All three immune clocks demonstrated significantly advanced immune aging in people with Down syndrome. Notably, one of these clocks, informed by Down syndrome-relevant biology, also showed advanced immune aging in people with type 1 diabetes. Together, our findings demonstrate a novel approach to studying immune aging in Down syndrome which may have implications in the context of other autoimmune diseases.

One Sentence Summary

Permutational analysis of immune landscape reveals advanced immune aging in people with Down syndrome and in people with type 1 diabetes.
Plant defense synergies and antagonisms affect performance of specialist herbivores of common milkweed
Authors: Edwards Collin , Ellner Stephen , Agrawal Anurag
Published: September 2021

As a general rule, plants defend against herbivores with multiple traits. The defense synergy hypothesis posits that some traits are more effective when co-expressed with others compared to their independent efficacy. However, this hypothesis has rarely been tested outside of phytochemical mixtures, and seldom under field conditions. We tested for synergies between multiple defense traits of common milkweed(Asclepias syriaca)by assaying the performance of two specialist chewing herbivores on plants in natural populations. We employed regression and a novel application of Random Forests to identify synergies and antagonisms between defense traits. We found the first direct empirical evidence for two previously hypothesized defense synergies in milkweed (latex by secondary metabolites, latex by trichomes), and identified numerous other potential synergies and antagonisms. Our strongest evidence for a defense synergy was between leaf mass per area and low nitrogen content; given that these “leaf economic” traits typically covary in milkweed, a defense synergy could reinforce their co-expression. We report that each of the plant defense traits showed context-dependent effects on herbivores, and increased trait expression could well be beneficial to herbivores for some ranges of observed expression. The novel methods and findings presented here complement more mechanistic approaches to the study of plant defense diversity, and provide some of the best evidence to date that multiple classes of plant defense synergize in their impact on insects. Plant defense synergies against highly specialized herbivores, as shown here, are consistent with ongoing reciprocal evolution between these antagonists.
Model-based characterization of the selectivity of neurons in primary visual cortex
Authors: Bartsch Felix , Cumming Bruce G. , Butts Daniel A.
Published: September 2021

To understand the complexity of stimulus selectivity in primary visual cortex (V1), models constructed to match observed responses to complex time-varying stimuli, instead of to explain responses to simple parametric stimuli, are increasingly used. While such models often can more accurately reflect the computations performed by V1 neurons in more natural visual environments, they do not by themselves provide insight into established measures of V1 neural selectivity such as receptive field size, spatial frequency tuning and phase invariance. Here, we suggest a series of analyses that can be directly applied to encoding models to link complex encoding models to more interpretable aspects of stimulus selectivity, applied to nonlinear models of V1 neurons recorded in awake macaque in response to random bar stimuli. In linking model properties to more classical measurements, we demonstrate several novel aspects of V1 selectivity not available to simpler experimental measurements. For example, we find that individual spatiotemporal elements of the V1 models often have a smaller spatial scale than the overall neuron sensitivity, and that this results in non-trivial tuning to spatial frequencies. Additionally, our proposed measures of nonlinear integration suggest that more classical classifications of V1 neurons into simple versus complex cells are spatial-frequency dependent. In total, rather than obfuscate classical characterizations of V1 neurons, model-based characterizations offer a means to more fully understand their selectivity, and provide a means to link their classical tuning properties to their roles in more complex, natural, visual processing.

Significance statement

Visual neurons are increasingly being studied with more complex, natural visual stimuli, with increasingly complex models necessary to characterize their response properties. Here, we describe a battery of analyses that relate these more complex models to classical characterizations. Using such model-based characterizations of V1 neurons furthermore yields several new insights into V1 processing not possible to capture in more classical means to measure their visual selectivity.
Mechanisms of loading and release of the 9-1-1 checkpoint clamp
Authors: Castaneda Juan C. , Schrecker Marina , Remus Dirk , Hite Richard K.
Published: September 2021

5’ single-stranded/double-stranded DNA serve as loading sites for the checkpoint clamp, 9-1-1, which mediates activation of the apical checkpoint kinase, ATRMec1. However, the basis for 9-1-1’s recruitment to 5’ junctions is unclear. Here, we present structures of the yeast checkpoint clamp loader, Rad24-RFC, in complex with 9-1-1 and a 5’ junction and in a post-ATP-hydrolysis state. Unexpectedly, 9-1-1 adopts both closed and planar open states in the presence of Rad24-RFC and DNA. Moreover, Rad24-RFC associates with the DNA junction in the opposite orientation of processivity clamp loaders with Rad24 exclusively coordinating the double-stranded region. ATP hydrolysis stimulates conformational changes in Rad24-RFC, leading to disengagement of DNA-loaded 9-1-1. Together, these structures explain 9-1-1’s recruitment to 5’ junctions and reveal new principles of sliding clamp loading.
High-quality genome assembly of Cinnamomum burmannii (chvar. Borneol) provides insights into the natural borneol biosynthesis
Authors: Li Fangping , Huang Shilin , Mei Yu , Wu Bingqi , Hou Zhuangwei , Zhan Penglin , Cai Shike , Liu Qingmei , Hou Zhihao , Zhao Junliang , Wang Jihua
Published: September 2021

Cinnamomum burmannii (chvar. Borneol) is a well-known medicinal and industrial plant cultivated in the Lingnan region of China. It is the key source from organism of natural borneol (D-borneol), one of the precious and widely used Chinese herbal medicines with a variety of medicinal effects. Here, we report a high-quality chromosome-scale genome assembly of C. burmannii (chvar. Borneol) using Pacbio single-molecule sequencing and Hi-C technology. The assembled genome size was 1.14 GB with a scaffold N50 of 94.30 Mb, while 98.77% of the assembled sequences were anchored on 12 pseudochromosomes including 41549 protein-coding genes. Genomic evolution analysis revealed C. burmannii and C. micranthum shared two Lauraceae unique ancestral whole-genome duplication (WGD) events. Likewise, comparative genomic analysis showed strong collinearity between these two species. Besides, the analysis for Long Terminal Repeat Retrotransposons (LTR-RTs) indicated the outbreak of LTR-RTs insertion made a great contribution to the size difference of genomes between C. burmannii and C. micranthum. Furthermore, the candidate genes in pathway associated with natural borneol synthesis were identified on the genome and their differential expressions were analyzed in various biological tissues. We considered that several of genes in Mevalonate (MVA) Methylerythritol Phosphate (MEP) pathways or in downstream pathway have the potential to be the key factors in the biosynthesis of D-borneol. We also constructed the genome database (CAMD; http://www.cinnamomumdatabase.com/) of Cinnamomum species for a better data utilization in the future. All these results will enrich the genomic data of Lauraceae plants and facilitate genetic improvement of this commercially important plant.
Mapping vegetation types in Antarctic Peninsula and South Shetlands islands using Sentinel-2 images and Google Earth Engine cloud computing
Authors: Lima da Fonseca Eliana , Casagrande dos Santos Edvan , Ribeiro de Figueiredo Anderson , Simões Jefferson Cardia
Published: September 2021

The Antarctic vegetation maps are usually made using very high-resolution images collected by orbital sensors or unmanned aerial vehicles, generating isolated maps with information valid only for the time of image acquisition. In the context of global environmental change, mapping the current Antarctic vegetation distribution on a regular basis is necessary for a better understanding of the changes in this fragile environment. This work aimed to generate validated vegetation maps for the North Antarctic Peninsula and South Shetlands Islands based on Sentinel-2 images using cloud processing. Sentinel-2 imagery level 1C, acquired between 2016 and 2021 (January-April), were used. Land pixels were masked with the minimum value composite image for the “water vapor” band. The NDVI maximum value composite image was sliced, and its classes were associated with the occurrence of algae (0.15 – 0.20), lichens (0.20 – 0.50), and mosses (0.50 – 0.80). The vegetation map was validated by comparing it with those from the literature. The present study showed that Sentinel-2 images allow building a vegetation type distribution map for Antarctica Peninsula and South Shetlands Islands.