bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic value of lacrimal scintigraphy in the evaluation of lacrimal drainage system obstruction: a systematic review and meta-analysis
Authors: Mirshahvalad Seyed Ali , Chavoshi Mohammadreza , Bahmani Kashkouli Mohsen , Fallahi Babak , Emami-Ardakani Alireza , Manafi-Farid Reyhaneh
Published: May 2022

Purpose

A systematic review and meta-analysis to evaluate the diagnostic performance of lacrimal scintigraphy (LS) versus anatomical methods in the evaluation of the nasolacrimal duct obstruction (NLDO).

Materials and methods

A systematic search was performed using electronic bibliographic databases until the end of May 2021. Inclusion criteria: (a) used LS as a diagnostic method to evaluate NLDO; (b) used anatomical studies [including syringing, irrigation, probing, and dacryocystography (DCG)] as reference tests; and (c) provided adequate crude data. A hierarchical method was used to pool the sensitivity and specificity. The hierarchical summary receiver-operating characteristic model was performed. Additionally, the studies’ heterogeneity and publication bias were analyzed. All analyses were conducted by the ‘Midas’ module of STATA 16.

Results

Twelve articles (with 14 separate populations) were considered eligible to enter the meta-analysis. They were divided into two groups based on the reference standard method, called irrigation and DCG groups. In the irrigation group, the pooled sensitivity and specificity were 89% [95% confidence interval (CI), 72–96%] and 25% (95% CI, 8–56%), respectively. In DCG group, the pooled sensitivity and specificity were 97% (95% CI, 85–100%) and 27% (95% CI, 0.12–0.49), in turn.

Conclusion

LS is a sensitive modality to evaluate the anatomical obstruction of NLD. In contrast, it shows low pooled specificity compared with anatomical methods. Thus, LS can be used as the first noninvasive modality for the evaluation of epiphora. However, in case of any abnormality, confirmatory procedures are required.
The New Mexico Nursing Education Consortium
Authors: Liesveld Judy
Published: May 2022

With shortfalls of thousands of nurses throughout the United States, the need for nursing students to graduate and enter the workforce was critical even prior to the COVID-19 pandemic. Innovative nursing education models are needed to mitigate the staggering shortfall. For over 10 years, the New Mexico Nursing Education Consortium (NMNEC) has been recognized as a successful pathway for students to achieve nursing degrees. The NMNEC is a collaborative partnership between university and community college nursing programs who offer a common curriculum and share common academic policies. Students in the community college setting choose an associate degree program or a co-enrolled associate degree/bachelor of science in nursing program. The NMNEC currently includes 16 nursing program sites throughout the state. The development of the NMNEC including its infrastructure, leadership council, committees, and involvement of program directors has contributed to the strength. The outcomes of NMNEC's nursing graduates have been exceptional with strong progression and NCLEX pass percentages. Since NMNEC's inception, diversity and health equity have been strong components of the NMNEC model and curriculum. The NMNEC model provides equity to students at rural community colleges to achieve a bachelor of science degree while remaining in their home settings.
Suicide Among Women and the Role of Women’s Health Care Providers
Authors: Stacy Meaghan , Kremer Mallory , Schulkin Jay
Published: May 2022

Importance

Suicide is a leading cause of death in the United States, with increasing rates among women. Women are more likely to experience suicidal ideation and engage in suicide behavior than men, and risk is elevated at key points where they may engage in care with a women's health care provider.

Objective

This review describes the prevalence of and risk factors for suicide among women and highlights the role of obstetrician-gynecologists in suicide prevention.

Evidence Acquisition

A PubMed, MEDLINE, and PsycINFO search was completed for English-language publications about suicide among women, including subtopics (eg, perinatal suicide, suicide during perimenopause).

Results

There are overlapping risk factors that contribute to suicide among women, including intimate partner violence and substance use. Specific groups of women may present with unique risk factors, such as women veterans, women in rural areas, and women with preexisting mental health diagnoses, particularly serious mental illnesses. Some women at risk for suicide are not seen in clinical settings, and thus community interventions may be beneficial. There are roles for obstetrician-gynecologists within and outside of the clinic to prevent suicide.

Conclusions and Relevance

Obstetrician-gynecologists can save lives by being aware of the prevalence of suicide ideation and behavior among women, understanding risk factors for suicide over the lifespan, regularly screening for these factors, asking directly about suicide ideation and intent, and being aware of clinical and community resources. Outside of the clinic, they can advocate for increased health care access and community-based interventions. These efforts can contribute to the reduction of preventable death and maternal mortality.

Target Audience

Obstetricians and gynecologists, family physicians.

Learning Objectives

After participating in this activity, physicians should be better able to distinguish how the prevalence of suicide in the United States varies across major demographic groups, including women; list factors associated with the greater prevalence of suicidal ideation and behavior among women; and identify the unique suicide risk factors among women across the reproductive life span, including pregnancy and the postpartum period.
Medications Without Borders
Authors: Chang Elizabeth L. , Kline Matthew D. , Sundararajan Radhika , Nguyen Margaret B.
Published: May 2022

Objective

This study aimed to identify motivating factors in why parents administer imported medications to their children.

Methods

In this qualitative study, we enrolled caregivers of patients younger than 18 years who presented for care at a pediatric emergency department. The study team conducted face-to-face interviews with caregivers in the emergency department and used a semistructured question guide to probe for themes regarding the use of imported medications in children. Interviews were recorded, transcribed, translated if necessary, and coded. We applied grounded theory methodology to assess for themes and adapted the Andersen model of health care utilization to provide a framework for the identified themes.

Results

We completed 30 interviews, 9 of which were conducted in Spanish. Themes surrounding imported medication usage were categorized into predisposing, enabling, and need factors. Predisposing factors included perception that an ill child needs medication to get better, perception of medication quality, and past experiences with medications. Enabling factors included proximity to foreign countries, cost, limited access to primary care, and convenience of obtaining medications. Need factors included utilization of foreign medications for a “simple illness” and utilization of foreign care for a “second opinion.”

Conclusions

Our study used qualitative methodology to gain important insights into the caregiver experience of a diverse patient population. We identify themes not previously published in the medication importation literature. These concepts can provide insights in educational strategies aimed at mitigating the potential dangers of imported medication use in pediatrics.
Emergency Department Visits by Pediatric Patients for Snakebites
Authors: Tadros Allison , Sharon Melinda , Davis Stephen , Quedado Kimberly , Marple Emily
Published: May 2022

Objectives

Few studies have examined pediatric emergency department (ED) visits for snakebites. This study sought to examine characteristics of pediatric patients presenting to EDs nationally in the United States for snakebites.

Methods

This retrospective cohort study obtained data from the Nationwide Emergency Department Sample for 2006 to 2014. Pediatric patients sustaining a snakebite were identified with International Classification of Diseases, Ninth Revision, E-codes E905.0 or E906.2. Data extracted included age, sex, insurance, disposition, hospital trauma designation, ED charges, and geographic region. Comparative analyses were performed for patients younger than 10 years and aged 10 to 17 years.

Results

There were 24,388 ED visits from 2006 to 2014 by pediatric patients for snakebites: 10,554 were younger than 10 years, and 13,834 were aged 10 to 17 years. Males comprised 62% and 67% of the respective age cohorts. Most patients (younger than 10 years, 68%; aged 10–17 years, 63%) experienced snakebites in the South. Only 14% of those younger than 10 years and 10% of those aged 10 to 17 years were treated at a level 1 trauma center, whereas 50% and 54%, respectively, were treated at hospitals with no trauma designation. The majority of patients were discharged from the ED (younger than 10 years, 72%; aged 10–17 years, 80%). The mean ED charges for snakebite victims younger than 10 years were $5363 and for those aged 10 to 17 years were $4618. Medicaid was the primary insurer of younger patients, whereas private insurance was more common in older patients.

Conclusions

Most pediatric snakebites are seen in nontrauma centers and in the South region and are more commonly male. Most patients were discharged from the ED, with a small percentage being admitted or transferred to another facility.
Single-Dose Dexamethasone Is Not Inferior to 2 Doses in Mild to Moderate Pediatric Asthma Exacerbations in the Emergency Department
Authors: Martin Meghan , Penque Michelle , Wrotniak Brian H. , Qiao Haiping , Territo Heather
Published: May 2022

Objective

The purpose of this study was to compare the efficacy of a single dose of dexamethasone to 2 doses of dexamethasone in treating mild to moderate asthma exacerbations in pediatric patients. We anticipated that there would not be a difference in the rate of return visits to the emergency department (ED), urgent care, or primary care physician for continued asthma symptoms.

Methods

This was a prospective, randomized, single-center, unblinded, parallel-group randomized clinical trial of patients 2 to 20 years old presenting to a pediatric ED with mild to moderate asthma exacerbations. The patients were randomized to receive 1 or 2 doses of dexamethasone (0.6 mg/kg per dose, maximum of 16 mg). Telephone follow-up interviews were performed on the sixth day after ED visit. The primary outcome measures were return visits to either primary care physician or ED for continued asthma symptoms. Secondary outcomes were days of symptoms, missed school days, and adverse effects.

Results

Of the 318 children initially enrolled, 308 patients met the enrollment criteria. These patients were randomized into 2 groups. There were 116 patients in group 1 and 116 patients in group 2. There was no significant difference between groups regarding return visits (group 1, 12.1%; group 2, 10.3%; odds ratio [OR], 0.892 [95% confidence interval {CI}, 0.377–2.110]), days to symptom resolution (group 1, 2.4; group 2, 2.5; OR, 0.974 [95% 95% CI, 0.838–1.132]), missed school days (group 1, 47%; group 2, 51%; OR, 1.114 [95% CI, 0.613–2.023]), or vomiting (group 1, 8.6%; group 2, 3.4%; OR, 2.424 [95% CI, 0.637–9.228]).

Conclusions

In this single-center, unblinded randomized trial of children and adolescents with mild to moderate acute exacerbations of asthma, there was no difference in the rate of return visits for continued or worsened symptoms between patients randomized to 1 or 2 doses of dexamethasone.
Discrepancies Between the Management of Fever in Young Infants Admitted From Urban General Emergency Departments and Pediatric Emergency Departments
Authors: Jain Priya Narayanan , Lerer Rikah , Choi Jaeun , Dunbar Julie , Eisenberg Ruth , Hametz Patricia , Nassau Stacy , Katyal Chhavi
Published: May 2022

Introduction/Objective

Most pediatric emergency visits occur in general emergency departments (GED). Our study aims to assess whether medical decision making regarding the management of febrile infants differs in GEDs from pediatric EDs (PED) and deviates from pediatric expert consensus.

Methods

We conducted a retrospective chart review on patients younger than 60 days with fever admitted from 13 GEDs versus 1 PED to a children’s hospital over a 3-year period. Adherence to consensus guidelines was measured by frequency of performing critical components of initial management, including blood culture, urine culture, attempted lumbar puncture, and antibiotic administration (<29 days old), or complete blood count and/or C-reactive protein, blood culture, and urine culture (29–60 days old). Additional outcomes included lumbar puncture, collecting urine specimens via catheterization, and timing of antibiotics.

Results

A total of 176 patient charts were included. Sixty-four (36%) patients were younger than 29 days, and 112 (64%) were 29 to 60 days old. Eighty-eight (50%) patients were admitted from GEDs.

In infants younger than 29 days managed in the GEDs (n = 32), 65.6% (n = 21) of patients underwent all 4 critical items compared with 96.9% (n = 31, P = 0.003) in the PED. In infants 29 to 60 days old managed in GEDs (n = 56), 64.3% (n = 36) patients underwent all 3 critical items compared with 91.1% (n = 51, P < 0.001) in the PED.

Conclusions

This retrospective study suggests that providers managing young infants with fever in 13 GEDs differ significantly from providers in the PED examined and literature consensus. Inconsistent testing and treatment practices may put young infants at risk for undetected bacterial infection.
Efficacy of a Self-managed Cooling Intervention for Pain and Physical Activity in Individuals With Recently Healed Chronic Venous Leg and Diabetic Foot Ulcers
Authors: Kelechi Teresa J. , Mueller Martina , Madisetti Mohan , Prentice Margaret
Published: May 2022

PURPOSE:

This aim of this study was to evaluate the clinical efficacy of a self-managed cooling intervention in individuals with recently healed venous leg ulcers (VLUs) and diabetic foot ulcers (DFUs) on pain reduction and physical activity improvement.

DESIGN:

A 6-month longitudinal randomized controlled trial.

SUBJECTS AND SETTING:

The sample comprised 140 individuals with previously healed VLU and DFU who received care in 3 outpatient wound centers in the Southeastern region of the United States. Participants were randomized to the MUSTCOOL or a placebo cooling patch intervention.

METHODS:

The cooling and placebo interventions comprised cooling or cotton-filled patch application to recently healed skin for 30 minutes, 3 times weekly plus standard of care including compression and leg elevation (participants with VLU) or therapeutic footwear and hygiene (participants with DFU) over a 6-month period. Pain severity and intensity were measured with the Brief Pain Inventory and physical activity with the International Physical Activity Questionnaire, which assessed metabolic equivalent of tasks (METs) in minutes per week. Minutes in walking time per week were assessed with an accelerometer. Data were descriptively analyzed for difference changes in scores from baseline to 6 months post-intervention.

RESULTS:

Data were analyzed for 81 participants randomized to cooling and placebo groups (VLUs, n = 26/29) and DFU (n = 12/16). Slight reductions in VLU pain severity (−0.5, −0.2) and interference (−0.4, −0.5) and minimal reductions in DFU pain severity (0, −0.1) and interference (0.4/0.1) were achieved. However, pain scores were low to moderate at baseline (mean 4, 0-10 with 10 worst pain possible) in both groups. For physical activity, the MET values showed low physical activity in both groups at baseline with slight improvements noted in VLU cooling and placebo groups (73/799) and DFU (1921/225), respectively. Walking time for the VLU groups improved by 1420/2523 minutes; the DFU groups improved 135/157 minutes, respectively. Findings for outcomes were not statistically significant within or between groups.

CONCLUSIONS:

Application of the cooling pack compared to placebo was minimally efficacious in reducing posthealing pain and improving function in this posthealed ulcer population. However for pain, scores were initially low; thus outcomes on pain, while lower, were marginal.

TRIAL REGISTRATION:

The study was prospectively registered with ClinicalTrials.gov on December 10, 2015 (Identifier: NCT02626156), https://clinicaltrials.gov/ct2/show/NCT02626156.
Ultra high-resolution biomechanics suggest that substructures within insect mechanosensors decisively affect their sensitivity
Authors: Dinges Gesa F. , Bockemühl Till , Iacoviello Francesco , Shearing Paul R. , Büschges Ansgar , Blanke Alexander
Published: May 2022

Insect load sensors, called campaniform sensilla (CS), measure strain changes within the cuticle of appendages. This mechanotransduction provides the neuromuscular system with feedback for posture and locomotion. Owing to their diverse morphology and arrangement, CS can encode different strain directions. We used nano-computed tomography and finite-element analysis to investigate how different CS morphologies within one location—the femoral CS field of the leg in the fruit flyDrosophila—interact under load. By investigating the influence of CS substructures' material properties during simulated limb displacement with naturalistic forces, we could show that CS substructures (i.e. socket and collar) influence strain distribution throughout the whole CS field. Altered socket and collar elastic moduli resulted in 5% relative differences in displacement, and the artificial removal of all sockets caused differences greater than 20% in cap displacement. Apparently, CS sockets support the distribution of distal strain to more proximal CS, while collars alter CS displacement more locally. Harder sockets can increase or decrease CS displacement depending on sensor location. Furthermore, high-resolution imaging revealed that sockets are interconnected in subcuticular rows. In summary, the sensitivity of individual CS is dependent on the configuration of other CS and their substructures.
An appetite for experiment: putting early Royal Society tastes back on the table
Authors: Holt Paddy
Published: May 2022

In 1665, Thomas Sprat's efforts to defend the hospitality bestowed on Samuel Sorbière, when the French savant visited London, were published in his
Letter containing some observations on Monsieur de Sorbier's voyage into England
. This book, for which Sprat stopped work on his now more famous
History of the Royal-Society
, challenged Sorbière's account of how he had been ‘entertained’, insisting he ‘be grateful for a good
potage
’ and ‘sound up his meat’. Experiments were, it seems, not to be depicted growing from nothing. This article thus situates Sprat's
Letter
amid convictions that the table was an apparently indispensable piece of experimental furniture. From the lavish banquets over which experiments were discussed, to feasts that were themselves experiments, it explores a learning seemingly nourished in rich settings of appetite and gratification. The offence caused by Sorbière's failure to acknowledge this commensality is placed in a context where, for better or worse, the character of experiment was on the table.
Exosome-derived small non-coding RNAs reveal immune response upon grafting transplantation in
Pinctada fucata
(Mollusca)
Authors: Huang Songqian , Nishiumi Shinya , Asaduzzaman Md , Pan Yida , Liu Guanting , Yoshitake Kazutoshi , Maeyama Kaoru , Kinoshita Shigeharu , Nagai Kiyohito , Watabe Shugo , Yoshida Tetsuhiko , Asakawa Shuichi
Published: May 2022

Exosomes, a subset of small extracellular vesicles, carry various nucleic acids, proteins, lipids, amino acids and metabolites. They function as a mode of intercellular communication and molecular transfer. Exosome cargo molecules, including small non-coding RNAs (sncRNAs), are involved in the immune response in various organisms. However, the role of exosome-derived sncRNAs in immune responses in molluscs remains unclear. Here, we aimed to reveal the sncRNAs involved in the immune response during grafting transplantation by the pearl oyster
Pinctada fucata
. Exosomes were successfully extracted from the
P. fucata
haemolymph during graft transplantation. Abundant microRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs) were simultaneously discovered in
P. fucata
exosomes by small RNA sequencing. The expression patterns of the miRNAs and piRNAs at the grafting and initial stages were not substantially different, but varied significantly between the initial and later stages. Target prediction and functional analysis indicate that these miRNAs and piRNAs are related to immune response upon grafting transplantation, whereas piRNAs may also be associated with transposon silencing by targeting with genome transposon elements. This work provides the basis for a functional understanding of exosome-derived sncRNAs and helps to gain further insight into the PIWI/piRNA pathway function outside of germline cells in molluscs.
A simple spatial extension to the extended connectivity interaction features for binding affinity prediction
Authors: Orhobor Oghenejokpeme I. , Rehim Abbi Abdel , Lou Hang , Ni Hao , King Ross D.
Published: May 2022

The representation of the protein-ligand complexes used in building machine learning models play an important role in the accuracy of binding affinity prediction. The Extended Connectivity Interaction Features (ECIF) is one such representation. We report that (i) including the discretized distances between protein-ligand atom pairs in the ECIF scheme improves predictive accuracy, and (ii) in an evaluation using gradient boosted trees, we found that the resampling method used in selecting the best hyperparameters has a strong effect on predictive performance, especially for benchmarking purposes.
The terminal enzymes of (bacterio)chlorophyll biosynthesis
Authors: Proctor Matthew S. , Sutherland George A. , Canniffe Daniel P. , Hitchcock Andrew
Published: May 2022

(Bacterio)chlorophylls are modified tetrapyrroles that are used by phototrophic organisms to harvest solar energy, powering the metabolic processes that sustain most of the life on Earth. Biosynthesis of these pigments involves enzymatic modification of the side chains and oxidation state of a porphyrin precursor, modifications that differ by species and alter the absorption properties of the pigments. (Bacterio)chlorophylls are coordinated by proteins that form macromolecular assemblies to absorb light and transfer excitation energy to a special pair of redox-active (bacterio)chlorophyll molecules in the photosynthetic reaction centre. Assembly of these pigment–protein complexes is aided by an isoprenoid moiety esterified to the (bacterio)chlorin macrocycle, which anchors and stabilizes the pigments within their protein scaffolds. The reduction of the isoprenoid ‘tail’ and its addition to the macrocycle are the final stages in (bacterio)chlorophyll biosynthesis and are catalysed by two enzymes, geranylgeranyl reductase and (bacterio)chlorophyll synthase. These enzymes work in conjunction with photosynthetic complex assembly factors and the membrane biogenesis machinery to synchronize delivery of the pigments to the proteins that coordinate them. In this review, we summarize current understanding of the catalytic mechanism, substrate recognition and regulation of these crucial enzymes and their involvement in thylakoid biogenesis and photosystem repair in oxygenic phototrophs.
Capnocytophaga tricuspid valve endocarditis: a case report and literature review
Authors: Hino Christopher , Veltman Jennifer
Published: May 2022

Capnocytophaga canimorsus

is a Gram-negative zoonotic pathogen capable of causing serious infection following dog or cat bite. Infections often manifest as sepsis, fatal septic shock, gangrene, bacteraemia, meningitis and endocarditis. Here we report a case of

C. canimorsus

bacteraemia complicated by tricuspid valve infective endocarditis and septic pulmonary emboli.
Genome analysis of Pseudomonas species reveals that Pseudomonas panacis Park et al. 2005 is a later heterotypic synonym of Pseudomonas marginalis (Brown 1918) Stevens 1925 (Approved Lists 1980)
Authors: Kujur Ritu Rani Archana , Deb Sushanta , Das Subrata K.
Published: May 2022

We described the comparative genomic analysis of

Pseudomonas panacis

DSM 18529T and

Pseudomonas marginalis

DSM 13124T of the genus

Pseudomonas

to define the taxonomic assignment. When conducting this analysis, genomic information for 203 type strains was available in the NCBI genome database. The ANI, AAI and isDDH data were higher than the threshold values between

Pseudomonas panacis

DSM 18529T and

Pseudomonas marginalis

DSM 13124T. Whole-genome comparisons show 97 % average nucleotide identity, 98 % average amino acid identity and 75 % in silico DNA–DNA hybridization values.

Pseudomonas marginalis

(Brown 1918) Stevens 1925 (Approved Lists 1980) have priority over the name

Pseudomonas panacis

Park et al. 2005, therefore nomenclatural authorities propose that

Pseudomonas panacis

Park et al. 2005 is a later heterotypic synonym of

Pseudomonas marginalis

(Brown 1918) Stevens 1925 (Approved Lists 1980). The type strain is ATCC 10844T (=DSM 13124T=NCPPB 667T).
Characterization of a new Blastobotrys navarrensis strain indicates that it is not a later synonym of Blastobotrys proliferans
Authors: Palma Margarida , Vieira Érica , Pataco Margarida , Sá-Correia Isabel
Published: May 2022

The species Blastobotrys navarrensis Sesma and Ramirez was delineated based on the description of the single strain CBS 139.77T. Based on its phenotypic similarities to Blastobotrys proliferans, B. navarrensis CBS 139.77T was later considered a synonym of B. proliferans. In the present study, we isolated the yeast strain IST 508 (=PYCC 8784=CBS 16671) from the soil surrounding an olive tree in Ferreira do Alentejo, Portugal. The phylogenetic analysis of D1/D2 domain and ITS sequences from strain IST 508 indicates that is closely related to B. navarrensis and B. proliferans. Although strain IST 508 differs from B. navarrensis CBS 139.77T by 14 substitutions and 20 indels (6.6 % divergence) in the ITS sequence, no divergence was detected at the level of D1/D2 domain, mitochondrial small subunit rDNA, and cytochrome oxidase II sequences. On the other hand, strains IST 508 and CBS 139.77 differ from B. proliferans NRRL Y-17577T by eight substitutions (1.4 % divergence) in the D1/D2 domain sequence, by 16 substitutions (2.7 % divergence) in the cytochrome oxidase II sequence, and by 16 substitutions (3.7 % divergence) in the mitochondrial small subunit rDNA sequence. Due to the high number of variable phenotypic tests in B. proliferans and B. navarrensis, strains from the two species are difficult to distinguish. Contrasting with what is described for other Blastobotrys species, no differences were detected at the level of micromorphology between the two species. Nevertheless, based on the molecular differences between the two strains, CBS 139.77 and IST 508, and B. proliferans NRRL Y-17577T and their phylogenetic analysis, strains CBS 139.77 and IST 508 are from B. navarrensis and this species should be considered as an independent species and not a later synonym of B. proliferans. We propose an emended description of B. navarrensis.
Mutations within scavenger receptor cysteine-rich (SRCR) protein domain 5 of porcine CD163 involved in infection with porcine reproductive and respiratory syndrome virus (PRRS)
Authors: Stoian Ana M. M. , Rowland Raymond R. R. , Brandariz-Nuñez Alberto
Published: May 2022

CD163, a macrophage-specific membrane scavenger receptor, serves as a cellular entry receptor for porcine reproductive and respiratory syndrome virus (PRRSV). The removal of scavenger receptor cysteine-rich (SRCR) domain 5 (SRCR5) of CD163 is sufficient to make transfected cells or genetically modified pigs resistant to PRRSV-1 and PRRSV-2 genotypes, and substitution of SRCR5 with SRCR8 from human CD163-like protein (hCD163L1) confers resistance to PRRSV-1 but not PRRSV-2 isolates. However, the specific regions within the SRCR5 polypeptide involved in PRRSV infection remain largely unknown. In this report, we performed mutational studies in order to identify which regions or amino acid sequences in the SRCR5 domain are critical for PRRSV infection. The approach used in this study was to make proline-arginine (PR) insertions along the SRCR5 polypeptide. Constructs were transfected into HEK293T cells, and then evaluated for infection with PRRSV-2 or PRRSV-1. For PRRSV-2, four PR insertions located after amino acids 8 (PR-9), 47 (PR-48), 54 (PR-55), and 99 (PR-100) had the greatest impact on infection. For PRRSV-1, insertions after amino acids 57 (PR-58) and 99 (PR-100) were critical. Computer simulations based on the crystal structure of SRCR5 showed that the mutations that affected infection localized to a similar region on the surface of the 3-D structure. Specifically, we found two surface patches that are essential for PRRSV infection. PR-58 and PR-55, which were separated by only three amino acids, had reciprocal effects on PRRSV-1 and PRRSV-2. Substitution of Glu-58 with Lys-58 reduced PRRSV-1 infection without affecting PRRSV-2, which partially explains the resistance to PRRSV-1 caused by the SRCR5 replacement with the homolog human SRCR8 previously observed. Finally, resistance to infection was observed following the disruption of any of the four conserved disulfide bonds within SRCR5. In summary, the results confirm that there are distinct differences between PRRSV-1 and PRRSV-2 on recognition of CD163; however, all mutations that affect infection locate on a similar region on the same face of SRCR5.
A One-Step Synthesis of DNA Dumbbells Tunnels Short-Read Libraries into a Long-Read Format
Authors: Chang Ya-Hui , Liu Hong-Hsing
Published: May 2022

DNA dumbbells have many applications. For example, they can be templates for rolling-circle amplification to produce highly accurate long-read sequences of single molecules. We have developed a highly efficient and simple method for ‘tunneling’ short-read Illumina sequencing libraries into long-read dumbbells. A 5’-exonuclease used in Gibson Assembly converted fixed Illumina P5/P7 sequences into sticky ends. Self-looping oligonucleotides with complementary 3’-overhangs were ligated to form dumbbells. The reaction proceeded in one pot and modified only end nucleotides of input libraries. Resulting dumbbells were ready for Phi29-dependent rolling circle amplification. Demonstrative readouts of full-length 16S rDNA from a standard microbial community, obtained on a Pacific Biosciences (PacBio) platform, confirmed successful tunneling of initially P5/P7-ended sequencing libraries. Twelve fecal samples additionally showed significant correlations between standard and tunneled 16S sequence variants on a PacBio platform.
Magnetic Resonance Imaging Radiomics-Based Model to Identify the Pathological Features and Lymph Node Metastasis in Rectal Cancer
Authors: Chen Peng , Wen Deying , Huang Libin , Ding Jingjing , Yang Wenming , Sun Jiayu , Yang Lie , Zhou Zongguang
Published: May 2022

Background

Pathological features and lymph node staging plays an important role in treatment decision-making. Yet, the preoperative accurate prediction of pathological features and lymph node metastasis (LNM) is challenging.

Objective

We aimed to investigate the value of MRI-based radiomics in predicting the pathological features and lymph node metastasis in rectal cancer.

Methods

In this prospective study, a total of 37 patients diagnosed with histologically confirmed rectal cancer who underwent pelvic 3.0T magnetic resonance imaging (MRI) were enrolled. MRI images of both the primary tumor alongside the lymph nodes and specimens were performed with a node-to-node match and labeling. The correlation analysis, least absolute shrinkage, and selection operator (LASSO) logistic regression (LR), backward stepwise LR were mainly used for radiomics feature selection and modeling. The univariate and multivariate backward stepwise LR were used for preoperative clinical predictors selection and modeling.

Results

A total of 487 lymph nodes including 39 metastatic lymph nodes and 11 tumor deposits were harvested from 37 patients. The texture features of the primary tumors could successfully predict tumor differentiation using a well-established model (area under the curve (AUC) = 0.798). Sixty-nine matched lymph nodes were randomly divided into a training cohort (n = 39) and a validation cohort (n = 30).

Three independent risk factors were obtained from 56 texture parameters closely related to LNM. A prediction model was then successfully developed, which provided AUC values of 0.846 and 0.733 in the training and test cohort, respectively. Further, tumor deposits produced a higher radiomics score (Rad-score) compared with LNM (P = 0.042).

Conclusion

The study provides two non-invasive and quantitative methods, which respectively predict the tumor differentiation and regional LNM for rectal cancer preoperatively. Ultimately, these are favorable when producing treatment protocols for rectal cancer patients.
Independent spatiotemporal effects of spatial attention and background clutter on human object location representations
Authors: Graumann Monika , Wallenwein Lara A. , Cichy Radoslaw M.
Published: May 2022

1.

Spatial attention helps us to efficiently localize objects in cluttered environments. However, the processing stage at which spatial attention modulates object location representations remains unclear. Here we investigated this question identifying processing stages in time and space in an EEG and fMRI experiment respectively. As both object location representations and attentional effects have been shown to depend on the background on which objects appear, we included object background as an experimental factor. During the experiments, human participants viewed images of objects appearing in different locations on blank or cluttered backgrounds while either performing a task on fixation or on the periphery to direct their covert spatial attention away or towards the objects. We used multivariate classification to assess object location information. Consistent across the EEG and fMRI experiment, we show that spatial attention modulated location representations during late processing stages (>150ms, in middle and high ventral visual stream areas) independent of background condition. Our results clarify the processing stage at which attention modulates object location representations in the ventral visual stream and show that attentional modulation is a cognitive process separate from recurrent processes related to the processing of objects on cluttered backgrounds.
Using Transfer Learning for Automated Microbleed Segmentation
Authors: Dadar Mahsa , Zhernovaia Maryna , Mahmoud Sawsan , Camicioli Richard , Maranzano Josefina , Duchesne Simon
Published: May 2022

Introduction

Cerebral microbleeds are small perivascular haemorrhages that can occur in both grey and white matter brain regions. Microbleeds are a marker of cerebrovascular pathology, and are associated with an increased risk of cognitive decline and dementia. Microbleeds can be identified and manually segmented by expert radiologists and neurologists, usually from susceptibility-contrast MRI. The latter is hard to harmonize across scanners, while manual segmentation is laborious, time-consuming, and subject to inter- and intra-rater variabiltiy. Automated techniques so far have shown high accuracy at a neighborhood (“patch”) level at the expense of a high number of false positives voxel-wise lesions. We aimed to develop an automated, more precise microbleeds segmentation tool able to use standardizable MRI contrasts.

Methods

We first trained a ResNet50 network on another MRI segmentations task (cerberospinal fluid versus background segmentation) using T1-weighted, T2-weighted, and T2* MRI. We then used transfer learning to train the network for the detection of microbleeds with the same contrasts. As a final step, we employed a combination of morphological operators and rules at the local lesion level to remove false positives. Manual segmentations of microbleeds from 78 participants were used to train and validate the system. We assessed the impact of patch size, freezing weights of the initial layers, mini-batch size, learning rate, as well as data augmentation on the performance of the Microbleed ResNet50 network.

Results

The proposed method achieved a high performance, with a patch-level sensitivity, specificity, and accuracy of 99.57%, 99.16%, and 99.93%, respectively. At a per lesion level, sensitivity, precision, and Dice similarity index values were 89.1%, 20.1%, and 0.28 for cortical GM; 100%, 100%, and 1.0 for deep GM; and 91.1%, 44.3%, and 0.58 for WM, respectively.

Discussion

The proposed microbleed segmentation method is more suitable for the automated detection of microbleeds with high sensitivity.
Thousands of human non-AUG extended proteoforms lack evidence of evolutionary selection among mammals
Authors: Fedorova Alla D. , Kiniry Stephen J. , Andreev Dmitry E. , Mudge Jonathan M. , Baranov Pavel V.
Published: May 2022

The synthesis of most proteins begins at AUG codons, yet a small number of non-AUG initiated proteoforms are also known. Here we used publicly available ribo-seq data with phylogenetic approaches to identify novel, previously uncharacterised non-AUG proteoforms. Unexpectedly we found that the number of non-AUG proteoforms identified with ribosome profiling data greatly exceeds those with strong phylogenetic support. We identified an association between proteoforms with alternative N-termini and multiple compartmentalisation of corresponding gene products. In dozens of genes N-terminal extensions encode localisation signals, including mitochondrial presequence and signal peptides. While the majority of non-AUG initiated proteoforms occur in addition to AUG initiated proteoforms, in few cases non-AUG appears to be the only start. This suggests that alternative compartmentalisation is not the only function of non-AUG initiation. Taking a conservative approach, we updated annotation of several genes in the latest GENCODE version in human and mouse where non-AUG initiated proteofoms are supported by both, ribosome profiling and phylogenetic evidence. Yet, the number of such extensions is likely much higher. Thousands of non-AUG proteoforms supported only by ribosome profiling suggest that they may evolve neutrally. Indeed, expression of some may not be consequential, i.e. when N-termini is processed or they have identical biochemical properties. Nonetheless they may contribute to immune response as antigen sources. It is also possible that some proteoforms accrued useful functions only recently and evolved under purifying selection in a narrow phylogenetic group. Thus, further characterisation is important for understanding their phenotypical and clinical significance.
Theory and application of an improved species richness estimator
Authors: Tekwa E. W. , Whalen Matthew A. , Martone Patrick T. , O’Connor Mary I.
Published: May 2022

Species richness is an essential biodiversity variable indicative of ecosystem states and rates of invasion, speciation, and extinction both contemporarily and in fossil records. However, limited sampling effort and spatial aggregation of organisms mean that biodiversity surveys rarely observe every species in the survey area, which introduces bias to the estimated richness and inaccuracy to comparisons of communities across space and time. Here we present a nonparametric, asymptotic, and bias-corrected richness estimator, ΩT, by modelling how spatial abundance characteristics affect observation of species richness. We conduct simulation tests and applied ΩT to a tree census and a seaweed survey. ΩT consistently outperforms common estimators in balancing bias, precision, and difference detection accuracy. Our results provide theoretical insights into how natural and observer-induced variation affects species observation and support ΩT as a promising and application-ready richness estimator for a wide variety of data.
Prediction of local convergent shifts in evolutionary rates with phyloConverge characterizes the phenotypic associations and modularity of regulatory elements
Authors: Saputra Elysia , Mao Weiguang , Clark Nathan , Chikina Maria
Published: May 2022

Physiological and morphological adaptations to extreme environments arise from the molecular evolution of protein-coding regions and regulatory elements (REs) that regulate gene expression. Comparative genomics methods can characterize genetic elements that underlie the organism-level adaptations, but convergence analyses of REs are often limited by their evolutionary properties. A RE can be modularly composed of multiple transcription factor binding sites (TFBS) that may each experience different evolutionary pressures. The modular composition and rapid turnover of TFBS also enables a compensatory mechanism among nearby TFBS that allows for weaker sequence conservation/divergence than intuitively expected. Here, we introduce phyloConverge, a comparative genomics method that can perform fast, fine-grained local convergence analysis of genetic elements. phyloConverge calibrates for local shifts in evolutionary rates using a combination of maximum likelihood-based estimation of nucleotide substitution rates and phylogenetic permutation tests. Using the classical convergence case of mammalian adaptation to subterranean environments, we validate that phyloConverge identifies rate-accelerated conserved non-coding elements (CNEs) that are strongly correlated with ocular tissues, with improved specificity compared to competing methods. We use phyloConverge to perform TFBS-scale and nucleotide-scale scoring to dissect each CNE into subregions with uneven convergence signals and demonstrate its utility for understanding the modularity and pleiotropy of REs. Subterranean-accelerated regions are also enriched for molecular pathways and TFBS motifs associated with neuronal phenotypes, suggesting that subterranean eye degeneration may coincide with a remodeling of the nervous system. phyloConverge offers a rapid and accurate approach for understanding the evolution and modularity of regulatory elements underlying phenotypic adaptation.
A transcriptional complex of FtMYB102 and FtbHLH4 coordinately regulates the accumulation of rutin in Fagopyrum tataricum
Authors: Mi Yaolei , Li Yu , Qian Guangtao , Vanhaelewyn Lucas , Meng Xiangxiao , Liu Tingxia , Yang Wei , Shi Yuhua , Ma Pengda , Wahab Atia tul , Chen Shilin , Sun Wei , Zhang Dong
Published: May 2022

Tartary buckwheat is rich in flavonoids, which not only play an important role in plant-environment interaction, but are also beneficial to human health. Rutin is a therapeutic flavonol which is massively accumulated in Tartary buckwheat. It has been demonstrated that transcription factors control rutin biosynthesis. However, the transcriptional regulatory network of rutin is not fully clear. In this study, through transcriptome and target metabolomics, we validated the role of FtMYB102 and FtbHLH4 TFs at the different developmental stages of Tartary buckwheat. The elevated accumulation of rutin in the sprout appears to be closely associated with the expression of FtMYB102 and FtHLH4. Yeast two-hybrid, transient luciferase activity and co-immunoprecipitation demonstrated that FtMYB102 and FtbHLH4 can interact and form a transcriptional complex. Moreover, yeast one-hybrid showed that both FtMYB102 and FtbHLH4 directly bind to the promoter of chalcone isomerase (CHI), and they can coordinately induce CHI expression as shown by transient luciferase activity assay. Finally, we transferred the FtMYB102 and FtbHLH4 into the hairy roots of Tartary buckwheat and found that they both can promote the accumulation of rutin. Our results indicate that FtMYB102 and FtbHLH4 can form a transcriptional complex by inducing CHI expression to coordinately promote the accumulation of rutin.
Kidney Transplant Recipients and Omicron: Outcomes, effect of vaccines and the efficacy and safety of novel treatments
Authors: Gleeson Sarah , Martin Paul , Thomson Tina , Thind Amarpreet , Prendecki Maria , Spensley Katrina J. , Clarke Candice L. , Roufosse Candice , Pickard Graham , Thomas David , McAdoo Stephen P. , Lightstone Liz , Kelleher Peter , Willicombe Michelle
Published: May 2022

We aimed to describe the outcomes of Omicron infection in kidney transplant recipients (KTR), compare the efficacy of the community therapeutic interventions and report the safety profile of molnupiravir.

From 142 KTRs diagnosed with COVID-19 infection after Omicron had become the dominant variant in the UK, 116 (78.9%) cases were diagnosed in the community; 47 receiving sotrovimab, 21 molnupiravir and 48 no treatment. 10 (20.8%) non-treated patients were hospitalised following infection, which was significantly higher than the sotrovimab group (2.1%), p=0.0048, but not the molnupiravir treated group (14.3%), p=0.47. The only admission following sotrovimab occurred in a patient infected with BA.2. One patient from the molnupiravir and no-treatment groups required ICU support, and both subsequently died, with one other death in the no-treatment group. No patient receiving sotrovimab died. 6/116 (5.2%) patients required dialysis following their diagnosis; 2 (9.5%) patients receiving molnupiravir and 4 (8.3%) no-treatment. This requirement was significantly higher in the molnupiravir group compared with the sotrovimab treated patients, in whom no patient required dialysis, p=0.035. Both molnupiravir treated patients requiring dialysis had features of systemic thrombotic microangiopathy.

Post-vaccination serostatus was available in 110 patients. Seropositive patients were less likely to require hospital admission compared with seronegative patients, 6 (7.0%) and 6 (25.0%) respectively, p=0.023. Seropositive patients were also less likely to require dialysis therapy, p=0.016.

In conclusion, sotrovimab treatment in the community was associated with superior patient and transplant outcomes; it’s clinical efficacy against the BA.2 variant requires a rapid review. The treatment benefit of molnupiravir was not evident, and wider safety reporting in transplant patients is needed.