bluuebunny/crossref_metadata_2025 huggingface dataset:
Interpretable spatial cell learning enhances the characterization of patient tissue microenvironments with highly multiplexed imaging data
Authors: Lu Peng , Oetjen Karolyn A. , Oh Stephen T. , Thorek Daniel L.J.
Published: March 2023

Multiplexed imaging technologies enable highly resolved spatial characterization of cellular environments. However, exploiting these rich spatial cell datasets for biological insight is a considerable analytical challenge. In particular, effective approaches to define disease-specific microenvironments on the basis of clinical outcomes is a complex problem with immediate pathological value. Here we present InterSTELLAR, a geometric deep learning framework for multiplexed imaging data, to directly link tissue subtypes with corresponding cell communities that have clinical relevance. Using a publicly available breast cancer imaging mass cytometry dataset, InterSTELLAR allows simultaneous tissue type prediction and interested community detection, with improved performance over conventional methods. Downstream analyses demonstrate InterSTELLAR is able to capture specific pathological features from different clinical cancer subtypes. The method is able to reveal potential relationships between these regions and patient prognosis. InterSTELLAR represents an application of geometric deep learning with direct benefits for extracting enhanced microenvironment characterization for multiplexed imaging of patient samples.
Predictive outcome models in ischemic stroke: Comparison of Latin American Stroke Registry and RESILIENT against models
Authors: Torrealba-Acosta Gabriel , Barboza-Elizondo Miguel , Arauz Antonio , Amaya Pablo F , Ameriso Sebastian F , Cano Vanessa , Flores-Flores Alan , Lavados Pablo M , Pujol-Lereis Virginia A , Serrano Fabiola , Martins Sheila , Nogueira Raul Gomes , Kent Thomas A , Mandava Pitchaiah
Published: March 2023

Introduction

Despite the significant stroke burden in the region, the RESILIENT trial remains the only randomized controlled trial (RCT) for stroke treatment in Latin America. Imbalances in baseline factors typically hamper comparisons between stroke populations. The Latin American Stroke Registry (LASE) is a registry of patients receiving tPA and thrombectomy from 17 centers across 9 countries. We compared the outcomes of LASE and RESILIENT at each cohort’s baseline characteristics against models derived from other RCTs.

Methods

A systematic search identified RCTs that provided median NIHSS, mean age, percentage of patients receiving tPA, time-to-randomization, 90-day mRS0-2, and mortality. Akaike Information Criterion (AIC) was used to select the best model amongst 31 combinations of 5 variables. 90-day outcomes of LASE and RESILIENT were compared at their baseline values against the selected model.

Results

35 RCTs encompassing 8376 subjects were identified. Models based on baseline NIHSS and the percentage of intravenous thrombolysis (IVT) were considered the most optimum in terms of AIC. The LASE registry included 950 patients receiving IVT alone, 127 that received IVT and mechanical thrombectomy (MT), and 101 receiving only MT. LASE & RESILIENT outcomes were plotted onto the models at their baseline values. LASE IVT alone group outcomes were in line with the RCT-informed model. LASE MT alone and MT + IVT, and the RESILIENT MT arm (68.5% IVT) demonstrated superior efficacy compared to no-MT. The RESILIENT control arm (71.8% tPA) had higher-than-expected mortality, while mortality of all other arms was within the predicted range.

Conclusion

Functional outcomes and mortality of patients from the LASE and RESILIENT trial receiving MT and MT+IVT compared favorably to the 90-day functional and mortality outcomes predicted in a model derived from no-MT data from other stroke RCTs, indicating Latin American MT systems of care are comparable to those of more resourceful regions. Higher mortality from IVT in the RESILIENT trial requires further investigation.
The genomics and evolution of inter-sexual mimicry and female-limited polymorphisms in damselflies
Authors: Willink B. , Tunström K. , Nilén S. , Chikhi R. , Lemane T. , Takahashi M. , Takahashi Y. , Svensson E. I. , Wheat C. W.
Published: March 2023

Sex-limited morphs can provide profound insights into the evolution and genomic architecture of complex phenotypes. Inter-sexual mimicry is one particular type of sex-limited polymorphism in which a novel morph resembles the opposite sex. While inter-sexual mimics are known in both sexes and a diverse range of animals, their evolutionary origin is poorly understood. Here, we investigated the genomic basis of female-limited morphs and male mimicry in the Common Bluetail damselfly. Differential gene expression between morphs has been documented in damselflies, but no causal locus has been previously identified. We found that male-mimicry originated in an ancestrally sexually-dimorphic lineage in association with multiple structural changes, probably driven by transposable element activity. These changes resulted in ∼900 kb of novel genomic content that is partly shared by male mimics in a close relative, indicating that male mimicry is a trans-species polymorphism. More recently, a third morph originated following the translocation of part of the male-mimicry sequence into a genomic position ∼3.5 mb apart. We provide evidence of balancing selection maintaining male-mimicry, in line with previous field population studies. Our results underscore how structural variants affecting a handful of potentially regulatory genes and morph-specific genes, can give rise to novel and complex phenotypic polymorphisms.
Intraspecific chemical variation ofTanacetum vulgareaffects plant growth and reproductive traits in field plant communities
Authors: Ojeda-Prieto Lina , Medina-van Berkum Pamela , Unsicker Sybille B. , Heinen Robin , Weisser Wolfgang W.
Published: March 2023

Intraspecific plant chemodiversity plays a fundamental role in interactions between plants and their interaction partners. However, how chemodiversity at the stand level (plant communities that vary in the number and type of plant chemotypes that grow in them, i.e., chemotype richness) affects ecosystem functioning is not fully understood.

We describe a biodiversity experiment using six chemotypes of common tansy (Tanacetum vulgareL., Asteraceae) to manipulate intraspecific plant chemodiversity at the plot level. We tested the effects of chemotype identity and plot-level chemotype richness (1-6) on plant growth and reproductive traits at plant and plot levels.

We found that chemotypes differed in growth and reproductive traits and that traits were affected by the plot-level chemotype richness. Although morphological differences became less pronounced over time, reproductive phenology patterns persisted. It suggests that chemotypes initially adopted different growth strategies, which may facilitate their establishment in nature.

Although chemotype richness did not lead to overyielding effects, plot-level trait means were affected by the presence or absence of certain chemotypes in a plot, and the direction of the effect depended on the chemotype.

We analyzed plot-level headspace emissions and found that blends released from plant communities were neither richer nor more diverse with increasing plot-level chemotype richness. However, we found that plots became more dissimilar in their headspace terpenoids as they were more dissimilar in their leaf-terpenoid profiles.

This long-term field experiment will allow further investigation into plant-insect interactions and insect community assembly in response to intraspecific chemodiversity.
A three filament mechanistic model of musculotendon force and impedance
Authors: Millard Matthew , Franklin David W. , Herzog Walter
Published: March 2023

The force developed by actively lengthened muscle depends on different structures across different scales of lengthening. For small perturbations, the active response of muscle is well captured by a linear-time-invariant (LTI) system: a stiff spring in parallel with a light damper. The force response of muscle to longer stretches is better represented by a compliant spring that can fix its end when activated. Experimental work has shown that the stiffness and damping (impedance) of muscle in response to small perturbations is of fundamental importance to motor learning and mechanical stability, while the huge forces developed during long active stretches are critical for simulating and predicting injury. Outside of motor learning and injury, muscle is actively lengthened as a part of nearly all terrestrial locomotion. Despite the functional importance of impedance and active lengthening, no single muscle model has all of these mechanical properties. In this work, we present the viscoelastic-crossbridge active-titin (VEXAT) model that can replicate the response of muscle to length changes great and small. To evaluate the VEXAT model, we compare its response to biological muscle by simulating experiments that measure the impedance of muscle, and the forces developed during long active stretches. In addition, we have also compared the responses of the VEXAT model to a popular Hill-type muscle model. The VEXAT model more accurately captures the impedance of biological muscle and its responses to long active stretches than a Hill-type model and can still reproduce the force-velocity and force-length relations of muscle. While the comparison between the VEXAT model and biological muscle is favorable, there are some phenomena that can be improved: the low frequency phase response of the model, and a mechanism to support passive force enhancement.
Altered muscle niche contributes to myogenic deficit in the D2-mdxmodel of severe DMD
Authors: Mázala Davi A. G. , Hindupur Ravi , Moon Young Jae , Shaikh Fatima , Gamu Iteoluwakishi H. , Alladi Dhruv , Panci Georgiana , Weiss-Gayet Michèle , Chazaud Bénédicte , Partridge Terence A. , Novak James S. , Jaiswal Jyoti K.
Published: March 2023

Lack of dystrophin is the genetic basis for the Duchenne muscular dystrophy (DMD). However, disease severity varies between patients, based on specific genetic modifiers. D2-mdxis a model for severe DMD that exhibits exacerbated muscle degeneration and failure to regenerate even in the juvenile stage of the disease. We show that poor regeneration of juvenile D2-mdxmuscles is associated with enhanced inflammatory response to muscle damage that fails to resolve efficiently and supports excessive accumulation of fibroadipogenic progenitors (FAPs). Unexpectedly, the extent of damage and degeneration of juvenile D2-mdxmuscle is reduced in adults and is associated with the restoration of the inflammatory and FAP responses to muscle injury. These improvements enhance myogenesis in the adult D2-mdxmuscle, reaching levels comparable to the milder (B10-mdx) mouse model of DMD.Ex vivoco-culture of healthy satellite cells (SCs) with the juvenile D2-mdxFAPs reduced their fusion efficacy andin vivoglucocorticoid treatment of juvenile D2 mouse improved muscle regeneration. Our findings indicate that aberrant stromal cell response contributes to poor myogenesis and greater muscle degeneration in dystrophic juvenile D2-mdxmuscles and reversal of this reduces pathology in adult D2-mdxmouse muscle, identifying these as therapeutic targets to treat dystrophic DMD muscles.
Structural characterization of a novel luciferase-like-monooxygenase fromPseudomonas meliae– an in-silico approach
Authors: Rayhan Mohammad , Siddiquee Mohd. Faijanur-Rob , Shahriar Asif , Ahmed Hossain , Mahmud Aar Rafi , Alam Muhammad Shaiful , Uddin Muhammad Ramiz , Acharjee Mrityunjoy , Shimu Mst. Sharmin Sultana , Shamsir Mohd. Shahir , Emran Talha Bin
Published: March 2023

Background

Luciferase is a well-known oxidative enzyme that produces bioluminescence. ThePseudomonas meliaeis a plant pathogen that causes wood rot on nectarine and peach and possesses a luciferase-like monooxygenase. After activation, it produces bioluminescence, and the pathogen’s bioluminescence is a visual indicator of diseased plants.

Methods

The present study aims to model and characterize the luciferase-like monooxygenase protein inP. meliaefor its similarity to well-established luciferase. In this study, the luciferase-like monooxygenase fromP. meliaeinfects chinaberry plants has been modeled first and then studied by comparing it with existing known luciferase. Also, the similarities between uncharacterized luciferase fromP. meliaeand template fromGeobacillus thermodenitrificanswere analyzed to find the novelty ofP. meliae.

Results

The results suggest that the absence of bioluminescence inP. meliaecould be due to the evolutionary mutation in positions 138 and 311. The active site remains identical except for two amino acids;P. meliaeTyr138 instead of His138 and Leu311 instead of His311. Therefore, theP. meliaewill have a potential future application, and mutation of the residues 138 and 311 can be restored luciferase light-emitting ability.

Conclusions

This study will help further improve, activate, and repurpose the luciferase fromP. meliaeas a reporter for gene expression.
The impact of FASTQ and alignment read order on structural variation calling from long-read sequencing data
Authors: Lesack Kyle , Wasmuth James D.
Published: March 2023

Background

Structural variation (SV) calling from DNA sequencing data has been challenging due to several factors, such as the ambiguity of short-read alignments, multiple complex SVs in the same genomic region, and the lack of “truth” datasets for benchmarking. Additionally, caller choice, parameter settings, and alignment method are known to affect SV calling. However, the impact of FASTQ read order on SV calling has not been explored for long-read data.

Results

In this study, we used PacBio DNA sequencing data from 15Caenorhabditis elegansisolates to evaluate the dependence of different SV callers on FASTQ read order. Comparisons of variant call format (VCF) files generated from the original and permutated FASTQ files demonstrated that the order of input data had a large impact on SV prediction, particularly for pbsv. The overall differences were lowest for Sniffles, regardless of the aligner used. The type of variant most affected by read order varied by caller. For pbsv, most differences occurred for deletions and duplications, while for Sniffles, permutating the read order had a stronger impact on insertions. For SVIM, inversions and deletions accounted for most differences.

Conclusion

The results of this study highlight the dependence of SV calling on the order of reads encoded in FASTQ files, which has not been recognized in long-read approaches. These findings have implications for the replication of SV studies and the development of consistent SV calling protocols. Our study suggests that researchers should pay attention to the order of reads when analyzing long-read sequencing data for SV calling.
Comparative Analysis of Tylosema esculentum Mitochondrial DNA Revealed Two Distinct Genome Structures
Authors: Li Jin , Cullis Christopher
Published: March 2023

Tylosema esculentum(marama bean), an underutilized legume with edible and nutritious seeds, has the potential to improve local food security in southern Africa. This study investigated the diversity of marama mitogenomes by mapping sequencing data from 84 individuals to the previously published reference mitogenome. Two distinct germplasms were found, and a new mitogenome structure containing three circular molecules and one long linear chromosome was identified, with a unique 2,108 bp fragment and primers were designed on that for marama mitogenome typing. This structural variation increases copy number of certain genes, includingnad9,rrnsandrrn5. The two mitogenomes also differed at 230 loci, with only one nonsynonymous substitution inmatR. The evolutionary analysis suggested that the divergence of marama mitogenomes may be related to soil moisture level. Heteroplasmy in the marama mitogenome was concentrated at specific loci, including 127,684 bp to 127,686 bp on chromosome LS1 (OK638188), and may be crucial in the evolution. Additionally, the mitogenomes of marama contained a cpDNA insertion of over 9 kb with numerous polymorphisms, resulting in the loss of function of the genes on that segment. This comprehensive analysis of marama mitogenome diversity may provide valuable insight for future improvement of the bean.

Highlight

The analysis of 84 marama mitogenomes revealed two germplasms and the structural variation affects certain gene copy numbers. Soil moisture levels may have played important roles in the mitogenome divergence.
Substrate reduction therapy in aDrosophila melanogastermodel of Sanfilippo syndrome
Authors: Tan Sher Li , Hewson Laura J. , Mustaffar Nooramirah Farhana , He Qi Qi , Wimmer Norbert , Trim Paul J. , King Barbara , Snel Marten F. , Hemsley Kim M. , Ferro Vito , O’Keefe Louise V. , Lau Adeline A.
Published: March 2023

Sanfilippo syndrome, or mucopolysaccharidosis (MPS) types A, B, C or D, are neurodegenerative lysosomal storage disorders resulting from the lack of a specific enzyme involved in heparan sulfate (HS) catabolism. Several treatments are under evaluation for these conditions including substrate reduction therapy, with the most studied compound of this class being the isoflavone genistein. However, recent outcomes from a Phase III clinical trial have shown that high dose oral genistein does not significantly improve neurodevelopmental outcomes in MPS III patients. Here, we have tested anN-acetylglucosamine (GlcNAc) analogue inhibitor, 4-deoxy-GlcNAc peracetate, at reducing HS accumulation in cells from patients with Sanfilippo syndrome as a novel substrate reduction therapy. We then confirmed the capacity of this compound to modulate substrate accumulationin vivoin a SanfilippoDrosophilamodel. Treatment with this compound significantly reduced HS in cultured MPS IIIA patient fibroblasts in a time-dependent manner. Neuronal and ubiquitous knockdownDrosophilamodels of MPS IIIC displaying elevated heparan sulfate and behavioural defects exhibited reduced HS burden relative to vehicle-treated controls following oral feeding with the GlcNAc analogue inhibitor. These findings indicate that this compound may be beneficial in slowing the accumulation of HS and may represent a novel therapeutic for Sanfilippo syndrome.
Understanding dynamics of respiration amongst sexes: who breathe more efficiently?
Authors: Himanshubhai Desai Dev , Dave Prahasth , Verma Anita , Mahajan Neeraj
Published: March 2023

Introduction

Respiration is a complex phenomenon requiring diaphragm, inter-costal muscles and other supporting structures. Contemplating the anatomical & physiological differences between males and females, it is essential to know how the respiratory system works in both of them. No such other study has been conducted in an Indian setup, which guided us to take up this topic.

Methodology

Total of N= 216 (Males 63, Females- 153) student were enrolled. All the participants were between the age of 17-19. Their data of Tidal volume, inspiratory reserve volume, expiratory reserve volume, maximum expiratory pressure and their vital capacity both sitting and standing were gathered and analysee.

Results

Tidal volume was in males 553±56 ml and 666±60 in females(p-value = 0.031). IRV was in males 2103±139 ml and 1717±99 in females(p-value>0.0001). ERV was in males 1638±113 ml and 1323±65 in females (p-value>0.0001). VC Standing was in males 3947±155 ml and 3278±105 in females(p-value>0.0001). VC sitting was in males 3492±151 ml and 2743±107 in females(pvalue>0.0001). MEP was in males 90±8 mmHg and 64±6 mmHg in females(p-value>0.0001).

Range of Pearson correlation coefficient for all=(+0.2)-(−0.2).

Conclusion

Tidal volume was found to be higher in females than in males. Vital capacity was higher in males than in females by 700 ml in both position and vital capacity was higher by 500ml in standing than in sitting in both males and females. Body mass index weakly correlatable positively or negatively with all parameters. MEP was found to be higher in males but was weakly correlated negatively with BMI.
Confidence in visual detection, familiarity and recollection judgements is preserved in schizophrenia spectrum disorder
Authors: Rouy Martin , Pereira Michael , Saliou Pauline , Sanchez Rémi , el Mardi Wassila , Sebban Hanna , Baqué Eugénie , Dezier Childéric , Porte Perrine , Micaux Julia , de Gardelle Vincent , Mamassian Pascal , Moulin Chris J.A. , Dondé Clément , Roux Paul , Faivre Nathan
Published: March 2023

An effective way to quantify metacognitive abilities is to ask participants to estimate their confidence in the accuracy of their response during a cognitive task. A recent meta-analysis1raised the issue that most assessments of metacognitive abilities in schizophrenia spectrum disorders may be confounded with cognitive deficits, which are known to be present in this population. Therefore, it remains unclear whether the reported metacognitive deficits are metacognitive in nature, or rather inherited from cognitive deficits. Arbitrating between these two possibilities requires equating task performance between experimental groups. Here, we aimed to characterize metacognitive performance among individuals with schizophrenia across three tasks (visual detection, familiarity, recollection) using a within-subject design, while controlling experimentally for intra-individual task performance and statistically for between-subject task performance. In line with our hypotheses, we found no metacognitive deficit for visual detection and familiarity judgements. While we expected metacognition for recollection to be specifically impaired among individuals with schizophrenia, we found evidence in favor of an absence of a deficit in that domain also. The clinical relevance of our findings is discussed in light of a hierarchical framework of metacognition.
Modeling Supraventricular Tachycardia Using Dynamic Computer-Generated Left Atrium
Authors: Wyatt Bryant , Campbell Avery , McIntosh Gavin , Little Melanie , Wyatt Brandon
Published: March 2023

Supraventricular Tachycardia (SVT) is a type of irregular heartbeat seen when the heart’s upper chambers beat either too quickly or out of rhythm with the heart’s lower chambers. The loss of synchronization between the upper and lower chambers will result in perturbations of, blood flow. This is why SVT, which includes atrial fibrillation and atrial flutter, is a leading cause of strokes, heart attacks, and heart failure in the world today. The most successful treatment for SVT is catheter ablation, a procedure in which an electrophysiologist (EP) maps the heart to find areas with abnormal electrical activity. The EP then runs a catheter into the heart to ablate the abnormal areas, blocking the electrical signals or destroying the myocytes causing them. Not much is known about what triggers SVT and much research is still being done to find effective ablation strategies for various forms of SVT. We have produced a dynamic model of the left atrium accelerated on NVIDIA GPUs. An interface allows researchers to insert ectopic signals into the simulated atrium and ablate sections of the atrium allowing them to rapidly gain insight into what causes SVT and how to terminate them.
Medication administration errors during general anesthesia – a systematic review of prospective studies
Authors: Murphy Bradley P , Sivaratnam Gayatri , Wong Jean , Chung Frances , Abrishami Amir
Published: March 2023

Introduction

The incidence of medication error in anesthesia can be variable among different studies likely due to recall bias in retrospective studies. In prospective survey studies, questionnaires are sent to anesthesia care providers to facilitate self-reports of medication errors during a pre-planned follow-up period. This systematic review investigates all prospective survey studies of medication errors in adult patients undergoing general anesthesia. Our objective is to identify the incidence and characteristics of the common medication errors during general anesthesia. We also want to determine the contributing factors and outcomes of these errors.

Methods

We conducted database searches of Embase and Medline for medication errors in anesthesia between 1980 to 2019 and 2020 to 2021. Ten prospective survey studies detailing medication errors involving adult patients under general anesthesia were included. Data on response rate, incidence of errors, types of error and medications, patient outcomes, and contributing factors were collected.

Results

Ten studies were included of which six studies provided a response rate ranging from 53% to 97.5%. The incidence of medication errors ranged from 0.02% to 1.12% or 1 in every 90 to 5000 anesthetics. A total of 1,676 medication errors during general anesthesia were analyzed. The most reported error was the substitution error (31.6% [530/1676]), followed by incorrect dose (28.4% [476/1676]). The class of medication most associated with administration errors were muscle relaxants, opioids, and antibiotics. Most patient outcomes were of no harm. Inexperience of the anesthesiologist, nurse or student was the most reported contributing factor, followed by haste or pressure to proceed, and communication problems.

Conclusion

The incidence of medication errors during general anesthesia were as high as 1.12% and the most common errors were substitution error and incorrect dose. Inexperience, time pressure, and communication problems were contributing factors. This information can be used to inform safety practices in anesthesia.
Clinically meaningful metrics of speech in neurodegenerative disease: Quantification of speech intelligibility and naturalness in ataxia
Authors: Vogel Adam P. , Maruff Paul , Reece Hannah , Carter Hannah , Tai Geneieve , Schultz Benjamin G. , Corben Louise , Delatycki Martin B , Tsanas Athanasios
Published: March 2023

Background

Digital biomarkers continue to make headway in the clinic and clinical trials for neurological conditions. Speech is a domain with great promise.

Objectives

Using Friedreich ataxia (FRDA) as an exemplar population, we aimed to align objective measures of speech with markers of disease severity, speech related quality of life and subjective judgements of speech using supervised machine learning techniques.

Methods

132 participants with genetically confirmed diagnosis of FRDA were assessed using digital speech tests, disease severity scores (Friedreich Ataxia Rating Scale, FARS) and speech related quality of life ratings over a 10-year period. Speech was analyzed perceptually by expert listeners for intelligibility (ability to be understood) and naturalness (deviance from healthy norm) and acoustically across 344 features. Features were selected and presented into a random forest and a support vector machine classifier in a standard supervised learning setup designed to replicate expert-produced scores.

Results

We demonstrate a subset of measures are strongly associated with all four clinical scales. Objective speech data replicated experts’ assessments of naturalness and intelligibility. These scores represent a lower level of variability than observed between subjective listener ratings. Findings provide evidence there are specific objective markers of speech that change over time and reflect clinical aspects of the disease.

Discussion

The use of a large dataset yielded a speech assay capable of accurately approximating expert listener ratings of key clinical aspects of dysarthria severity. Distinct but complementary subsets align with disease severity and speech related quality of life.
Informal payments in health facilities in Peru in 2018: analysis of a cross-sectional survey
Authors: Espinoza Laura A. , Mallma Patricia , Leslie Hannah H. , García Patricia J.
Published: March 2023

Background

The Latin American region demonstrates the lowest levels of trust in health systems globally. Institutional corruption is a major factor in eroding trust. Corruption in health services, including extracting bribes and informal payments from patients, directly harms health outcomes and weakens services intended as public goods. In this study, we aim to characterize the frequency and distribution of informal payments within public health services in Peru.

Methods

We conducted a secondary analysis of a nationally representative cross-sectional survey, the 2018 National Household Survey of Living Conditions and Poverty and identified all individuals reporting health insurance from the Ministry of Health (SIS-MINSA) or Social Security (ESSALUD). To assessed self-reported informal payments in the population, we defined it in 2 ways: 1) being asked to pay a bribe at a health establishment in the past year (direct method), and 2) non-zero cost of care for services that should be free (indirect method) in the last month. We used descriptive statistics to quantify informal payments and bivariate analysis to identify sociodemographic characteristics of those most frequently reporting such payments.

Findings

132,355 people were surveyed, including 69,839 (52.8%) with coverage from SIS-MINSA and 30,461 (23.03%) from ESSALUD. 39% of respondents reported informal payments in public health services. Less than 1% of participants directly reported them, either at SIS-MINSA services (0.22%); or at ESSALUD (0.42%). Indirect reporting was more prevalent, including up to 10% of surgery patients and 17% of those hospitalized in SIS-MINSA facilities. Wealthier patients (19%) were more likely to report such payments. Interpretation: While direct reporting of bribery was uncommon, we found moderate prevalence of informal payments in public health services in Peru using an indirect assessment method. Indirect reporting may exceed direct reporting due to difficulty in distinguishing appropriate and inappropriate payments, fear of reporting health care workers’ behavior, or social tolerance of informal payments. Informal payments were more common among those with greater social and financial capital, indicating they may obtain enhanced services. Further research on patients’ perception and reporting of informal payments is a key step towards accurate measurement and evidence-based intervention.
Built Environment Features Obtained from Google Street View Are Associated with Coronary Artery Disease Prevalence: A Deep-Learning Framework
Authors: Chen Zhuo , Khalifa Yassin , Dazard Jean-Eudes , Motairek Issam , Rajagopalan Sanjay , Al-Kindi Sadeer
Published: March 2023

Background

Built environment plays an important role in development of cardiovascular disease. Tools to evaluate the built environment using machine vision and informatic approaches has been limited. We sought to investigate the association between machine vision-based built environment and prevalence of cardiometabolic disease in urban cities.

Methods

This cross-sectional study used features extracted from Google Street view (GSV) images to measure the built environment and link them with prevalence of cardiometabolic disease. Convolutional neural networks, light gradient boosting machines and activation maps were utilized to predict health outcomes and identify feature associations with coronary heart disease (CHD). The study obtained 0.53 million GSV images covering 789 census tracts in 7 cities (Cleveland, OH; Fremont, CA; Kansas City, MO; Detroit, MI; Bellevue, WA; Brownsville, TX; and Denver, CO). Analyses were conducted from February 2022 to December 2022. We used census tract-level data from the Centers for Disease Control and Prevention’s PLACES dataset. Main outcomes included census tract-level estimated prevalence of CHD based on GSV built environment features.

Results

Built environment features extracted from GSV using deep learning predicted 63% of the census tract variation in CHD prevalence. The ExtraTrees Regressor achieved the best result among all models with the lowest average mean absolute error of 1.11% and Root mean square of error of 1.58. The addition of GSV features outperformed and improved a model that only included census-tract level age, sex, race, income and education. Activation maps from the features revealed a set of neighborhood features represented by buildings and roads associated with CHD prevalence.

Conclusions

In this cross-sectional study, a significant portion of CHD prevalence were explained by GSV-based built environment factors analyzed using deep learning, independent of census tract demographics. Machine vision enabled assessment of the built environment could help play a significant role in designing and improving heart-heathy cities.
Using photographs and deep neural networks to understand flowering phenology and diversity in mountain meadows
Authors: John Aji , Theobald Elli J. , Cristea Nicoleta , Tan Amanda , Hille Ris Lambers Janneke
Published: March 2023

Mountain meadows are an essential part of the alpine-subalpine ecosystem; they provide ecosystem services like pollination and are home to diverse plant communities. Changes in climate affect meadow ecology on multiple levels, for example by altering growing season dynamics. Tracking the effects of climate change on meadow diversity through the impacts on individual species and overall growing season dynamics is critical to conservation efforts. Here, we explore how to combine crowd sourced camera images with machine learning to quantify flowering species richness across a range of elevations in alpine meadows located in Mt Rainier National Park, Washington, USA. We employed three machine learning techniques (Mask R-CNN, RetinaNet and YOLOv5) to detect wildflower species in images taken during two flowering seasons. We demonstrate that deep learning techniques can detect multiple species, providing information on flowering richness in photographed meadows. The results indicate higher richness just above the tree line for most of the species, which is comparable with patterns found using field studies. We found that the two-stage detector Mask R-CNN was more accurate than single-stage detectors like RetinaNet and YOLO, with the Mask R-CNN network performing best overall with mean average precision (mAP) of 0.67 followed by RetinaNet (0.5) and YOLO (0.4). We found that across the methods using anchor box variations in multiples of 16 led to enhanced accuracy. We also show that detection is possible even when pictures are interspersed with complex backgrounds and are not in focus. We found differential detection rates depending on species abundance, with additional challenges related to similarity in flower characteristics, labeling errors, and occlusion issues. Despite these potential biases and limitations in capturing flowering abundance and location-specific quantification, accuracy was notable considering the complexity of flower types and picture angles in this data set. We therefore expect that this approach can be used to address many ecological questions that benefit from automated flower detection, including studies of flowering phenology and floral resources, and that this approach can therefore complement a wide range of ecological approaches (e.g., field observations, experiments, community science, etc.). In all, our study suggests that ecological metrics like floral richness can be efficiently monitored by combining machine learning with easily accessible publicly curated datasets (e.g., Flickr, iNaturalist).
Effect of caldesmon mutations in the development of zebrafish embryos
Authors: Virtanen Verneri , Paunu Kreetta , Niva Saana , Sundvall Maria , Paatero Ilkka
Published: March 2023

Cancer is a profound medical concern and better treatments are needed for cancer patients. Therefore, new cancer targets are constantly being studied. These targets need not only be relevant for cancer progression, but their modulation needs to be tolerated reasonably well by the host. Caldesmon is one of these proposed novel targets for cancer therapy. Therefore, we analysed effects of caldesmon mutations in normal development using genetically modified zebrafish embryos. We analysed mutations in both zebrafish caldesmon genes,cald1aandcald1band analysed effects of either mutation alone or as in combination in double homozygous embryos using molecular, morphological and functional analyses. The effects of caldesmon mutations were mild and the gross development of zebrafish embryos was normal. The caldesmon mutant embryos had, however, alterations in response to light-stimulus in behavioral assays. Taken together, the effects of caldesmon mutations in the development of zebrafish embryos were reasonably well tolerated and did not indicate significant concerns for caldesmon being a potential target for cancer therapy.
CREaTor: Zero-shotcis-regulatory pattern modeling with attention mechanisms
Authors: Li Yongge , Ju Fusong , Chen Zhiyuan , Qu Yiming , Xia Huanhuan , He Liang , Wu Lijun , Zhu Jianwei , Shao Bin , Deng Pan
Published: March 2023

Linkingcis-regulatory sequences to target genes has been a long-standing challenge. In this study, we introduce CREaTor, an attention-based deep neural network designed to modelcis-regulatory patterns for genomic elements up to 2Mb from target genes. Coupled with a training strategy that predicts gene expression from flanking candidatecis-regulatory elements (cCREs), CREaTor can model cell type-specificcis-regulatory patterns in new cell types without prior knowledge of cCRE-gene interactions or additional training. The zero-shot modeling capability, combined with the use of RNA-seq and ChIP-seq data only, allows for the readily generalization of CREaTor to a broad range of cell types. Evaluation reveals that CREaTor outperforms existing methods in capturing cCRE-gene interactions across various distance ranges in held-out cell types. Further analysis indicates that the superior performance of CREaTor can be attributed to its capacity to model regulatory interactions at multiple levels, including the higher-order genome organizations that govern cCRE activities as well as cCRE-gene interactions. Collectively, our findings highlight CREaTor as a powerful tool for systematically investigatingcis-regulatory programs across various cell types, both in normal developmental processes and disease-associated contexts.
High-level production of nervonic acid in the oleaginous yeastYarrowia lipolyticaby systematic metabolic engineering
Authors: Su Hang , Shi Penghui , Shen Zhaoshuang , Meng Huimin , Men Ziyue , Han Xingfeng , Chen Yanna , Fan Weiming , Fa Yun , Yang Chunyu , Li Fuli , Wang Shi’an
Published: March 2023

Brain and neurological diseases are influencing more than one billion world’s people. Nervonic acid (cis-15-tetracosenoic acid, C24:1 Δ15) benefits the treatment of neurological diseases and the health of brain. Currently, the sources of nervonic acid are limited to the seeds of a couple of plants. In this study, we employed the oleaginous yeastYarrowia lipolyticato overproduce nervonic acid oil by systematic metabolic engineering. First, engineering the fatty acid elongation (FAE) pathway by expressing a heterologous β-ketoacyl-CoA synthase geneCgKCSenabled the production of nervonic acid inY. lipolytica.Second, modulation of endogenous pathways by expressing a C16:0-acyl-CoA preferred fatty acid elongase gELOVL6 together with a C18:0-acyl-CoA preferred fatty acid desaturase MaOLE2 increased the content of nervonic acid in total fatty acids (TFA). Third, iterative expression ofCgKCS,gELOVL6andMaOLE2at the genomic loci ofrDNA,FAD2,TGL4,GSY1andSNF1dramatically improved the production of nervonic acid. Fourth, the biosynthesis of both nervonic acid and lipids were further enhanced by expression of the MaOLE2-CgKCS fusion protein and glycerol-3-phosphate acyltransferases (GPAT) and diacylglycerol acyltransferases (DGAT) fromMalania oleiferain the endoplasmic reticulum (ER) membrane. Fifth, an ER structure regulator YlINO2 was identified inY. lipolyticaand the overexpression of YlINO2 led to a 39.3% increase in lipid production. Next, pilot-scale fermentation in 50-L reactor using the strain YLNA9 exhibited a lipid titer of 96.7 g/L and a nervonic acid titer of 17.3 g/L, the highest reported titer to date forde novonervonic acid production. We also found that disruption of the AMP-activated S/T protein kinaseSNF1increased the ratio of nervonic acid (C24:1) to lignoceric acid (C24:0) by 61.6% and a ratio of 3.5:1 (nervonic acid to lignoceric acid) was achieved in the strain YLNA10. Finally, a proof-of-concept purification and separation of nervonic acid were performed and the purity of it reached 98.7%. This study suggested that oleaginous yeasts are attractive hosts for the cost-efficient production of nervonic acid and possibly other very long-chain fatty acids (VLCFAs).
Single-cell RNA-seq differential expression tests within a sample should use pseudo-bulk data of pseudo-replicates
Authors: Hafemeister Christoph , Halbritter Florian
Published: March 2023

Single-cell RNA sequencing (scRNA-seq) has become a standard approach to investigate molecular differences between cell states. Comparisons of bioinformatics methods for the count matrix transformation (normalization) and differential expression (DE) analysis of these data have already highlighted recommendations for effective between-sample comparisons and visualization. Here, we examine two remaining open questions: (i) What are the best combinations of data transformations and statistical test methods, and (ii) how do pseudo-bulk approaches perform in single-sample designs? We evaluated the performance of 343 DE pipelines (combinations of eight types of count matrix transformations and ten statistical tests) on simulated and real-world data, in terms of precision, sensitivity, and false discovery rate. We confirm superior performance of pseudo-bulk approaches without prior transformation. For within-sample comparisons, we advise the use of three pseudo-replicates, and provide a simple R packageDElegateto facilitate application of this approach.
Identification of Differentially Expressed Genes in Wheat NILs in Response to Leaf Rust Infection using In Silico Analysis
Authors: Kumar Rahul
Published: March 2023

In this study, the molecular basis of leaf rust resistance was investigated by examining the differential gene expression of wheat cultivar Thatcher, both with and without a leaf rust resistance gene, in response to rust infection. unigenes/ESTs databases were utilized belonging to three near-isogenic lines (NILs) of Thatcher, including Thatcher, Thatcher + Lr10, and Thatcher + Lr1, to identify differentially expressed unigenes (DEUs) in response to leaf rust. Sixty-eight DEUs were identified using a data mining tool called Digital Differential Display (DDD). Among these DEUs were specific unigenes associated with Lr1 and/or Lr10-mediated resistance, as well as unigenes expressed exclusively in compatible interactions. Our results suggest that photosynthesis, lignin, and antifungal proteins play a role in the leaf rust resistance mechanism, as indicated by the overexpression of Ribulose-1,5-bisphosphate carboxylase/oxygenase, caffeic acid O-methyltransferase, and Glutathione S-transferase unigenes, respectively. Our findings demonstrate both common and distinctive genetic pathways involved in rust resistance in the Lr1 and Lr10 NILs. The expression of most DEUs was found to be high in leaves, moderate in sheath, stem, and inflorescence, and low in seed, root, flower, crown, callus, and cell culture, indicating their role in leaf rust. Using high-throughput microarray gene expression data, a subset of DEUs was validated, and as a result, eleven unigenes were mapped to deletion bins on individual wheat chromosomes. These key genes may be used as molecular markers for genome editing, which could facilitate the development of leaf rust-resistant wheat cultivars.
Distinct sources and behavioral correlates of macaque motor cortical low and high beta
Authors: Nougaret Simon , López-Galdo Laura , Caytan Emile , Poitreau Julien , Barthelemy Frederic V , Kilavik Bjørg Elisabeth
Published: March 2023

HIGHLIGHTS

The low beta rhythm is dominant in M1 and the high beta rhythm in PMd

The beta rhythms correlate with task-instructed and uninstructed behavior

Low beta reflects movement preparation and spontaneous postural dynamics

High beta reflects temporal task prediction and dynamical visuospatial attention

Low and high beta frequency rhythms were observed in the motor cortex, but their respective sources and behavioral correlates remain unknown. We studied local field potentials during pre-cued reaching behavior in macaques. They contained a low beta band (<20Hz) dominant in primary motor cortex and a high beta band (>20Hz) dominant in dorsal premotor cortex. Low beta correlated positively with reaction time from visual cue onset, and negatively with uninstructed hand postural micro-movements throughout the trial. High beta reflected temporal task prediction, with selective modulations before and during cues, which were enhanced in moments of increased focal attention when the gaze was on the work area. This double-dissociation in sources and behavioral correlates of motor cortical low and high beta, with respect to both task-instructed and spontaneous behavior, reconciles the largely disparate roles proposed for the beta rhythm, by suggesting band-specific roles in both movement control and spatio-temporal attention.
A kernel integral method to remove biases in estimating trait turnover
Authors: Latombe Guillaume , Boittiaux Paul , Hui Cang , McGeoch Melodie
Published: March 2023

Trait diversity, including trait turnover, that differentiates the roles of species and communities according to their functions, is a fundamental component of biodiversity. Accurately capturing trait diversity is crucial to better understand and predict community assembly, as well as the consequences of global change on community resilience. Existing methods to compute trait turnover have limitations. Trait space approaches based on minimum convex polygons only consider species with extreme trait values. Tree-based approaches using dendrograms consider all species but distort trait distance between species. More recent trait space methods using complex polytopes try to harmonise the advantages of both methods, but their current implementation have mathematical flaws.

We propose a new kernel integral method (KIM) to compute trait turnover, based on the integration of kernel density estimators (KDEs) rather than using polytopes. We explore how this difference and the computational aspects of the KDE computation can influence the estimates of trait turnover. We compare our novel method to existing ones using justified theoretical expectations for a large number of simulations in which we control the number of species and the distribution of their traits. We illustrate the practical application of KIM using plant species introduced to the Pacific Islands of French Polynesia.

Analyses on simulated data show that KIM generates results better aligned with theoretical expectations than other methods and is less sensitive to the total number of species. Analyses for French Polynesia data also show that different methods can lead to different conclusions about trait turnover, and that the choice of method should be carefully considered based on the research question.

Mathematical aspects for computing trait turnover are crucial as they can have important effects on the results and therefore lead to different conclusions. Our novel kernel integral method generates values that better reflect the distribution of species in the trait space than other existing methods. We therefore recommend using KIM in future studies on trait turnover. In contrast, tree-based approaches should be kept for phylogenetic diversity, as phylogenetic trees will then reflect the constrained speciation process.