bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of warm needling therapy on symptoms of benign prostatic hyperplasia
Authors: Zhang Tao , Li Bin , Liu Hui-Lin , Wang Shao-Song , Zhang Fan , Du Xin , You Wei , Jia Lian-Cheng , Sun Jing-Qing
Published: December 2021

Background:

Benign prostatic hyperplasia (BPH) is the term for a type of non-malignant prostate enlargement that is most often diagnosed in men of middle age and older. Lower urinary tract symptoms (LUTS) are commonly observed in men afflicted with BPH. Evidence suggests that warm needling therapy could be applied clinically to relieve the LUTS associated with BPH, particularly in China, where experienced practitioners are readily available. In this review, the safety and effects of warm needling therapy are assessed in the context of treatment for LUTS associated with BPH.

Methods:

First, data for relevant randomised controlled trials and the initial periods of randomised cross-over trials will be obtained from four English databases (MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, and Allied and Complementary Medicine Database) and six Chinese databases (China National Knowledge Infrastructure, Wanfang Database, SinoMed, Chongqing VIP Chinese Science and Technology Periodical Database, China Master's Theses Full-text Database and China Doctoral Dissertations Full-text Database). The primary outcomes analysed in this protocol are improvements in urological symptoms as measured by recognized urological symptom scores, while secondary outcomes include improvement of urine flow rate measures, residual urine volume, nocturia, prostate size, and quality-of-life score. In addition, safety outcomes will be analysed by assessing incidences of adverse events. Two reviewers will independently assess and select studies, extract data and assess the risk of bias. Data synthesis and risk bias assessment will be performed with Review Manager software (version 5.3).

Results:

This systematic review provides a synthesis to assess the therapeutic efficacy of warm needling therapy for LUTS associated with BPH.

Conclusion:

The present study will provide a clinically relevant evaluation of the current state of evidence regarding the therapeutic efficacy of warm needling therapy for LUTS associated with BPH.

Ethics and dissemination:

Ethical approval is not required for this review, because private information will not be collected from the included participants. The results of the study will be published in a peer-reviewed journal.

Registration number:

PROSPERO CRD42020198360.
Clinico-radiological features of brain metastases from thyroid cancer
Authors: Kim Song Soo , Kim Seok-Mo , Park Mina , Suh Sang Hyun , Ahn Sung Jun
Published: December 2021

The brain is an unusual site for distant metastases of thyroid cancer. The radiological features of brain metastases (BMs) have rarely been reported. Hemorrhage is frequently noted in BMs from thyroid cancer. This study aimed to investigate the clinico-radiological features of BMs from thyroid cancer and to determine the risk factors to predict BM hemorrhage.

We retrospectively evaluated the MR images of 35 patients with BMs from thyroid cancer at our hospital from 2013 to 2020. The number, size, site, presence of extra-cranial metastasis, presence of perilesional edema, intra-tumoral hemorrhage, enhancement pattern, and presence of diffusion restriction on MRI were described. We further classified the thyroid cancers into hemorrhagic and nonhemorrhagic groups to investigate the factors associated with hemorrhage.

54.29% of patients with thyroid BMs (19/35) had neurologic symptoms. 94.29% of patients (33/35) had extra-cranial metastases. The most common histology of primary thyroid cancer was papillary thyroid cancer (71.43%, 25/35), followed by anaplastic thyroid cancer (22.86%, 8/35). Thyroid cancer BMs were located mostly in the supra-tentorium (51.43%, 18/35) or both the supra and infra-tentorium (45.71%, 16/35). 60% of patients (21/35) showed hemorrhage within the BMs. The strongest predictor for BM hemorrhage was tumor size (variable importance: 50).

Thyroid cancer BMs exhibit a bleeding tendency. Furthermore, larger BMs are more likely to have an intra-tumoral hemorrhage.
Antiphospholipid syndrome with mesenteric vein thrombosis and hepatic nodular regenerative hyperplasia in a child
Authors: Han Seung Hyung , Park Kyung Duk , Kim Soon Chul
Published: December 2021

Rationale:

Hepatic nodular regenerative hyperplasia (NRH), a nonspecific change in the liver parenchyma, is very rare in children. Hepatic microvascular changes may be the cause, as these vascular changes are uncommon in children. Antiphospholipid syndrome (APS), an autoimmune disease characterized by vascular thromboembolism, is extremely unusual in children.

Patient concerns:

A 13-year-old girl who presented with abdominal pain and elevated liver enzymes was transferred to our hospital. Abdominal computed tomography and magnetic resonance imaging showed a massive mesenteric venous thrombus and a malignant mass with liver metastasis.

Diagnoses:

Her immunological profile was positive for antinuclear antibodies (ANA) at a titer of 1/160 (nucleolar pattern), anticardiolipin antibodies (aCL) immunoglobulin G, and anti-histone antibody. A liver biopsy revealed hepatic NRH.

Interventions:

The patient was initially started on heparin upon hospitalization and switched to warfarin and a vitamin K antagonist and continued treatment with international normalized ratio monitoring.

Outcomes:

Her symptoms improved after 9 months of anticoagulation therapy.

Lessons:

In the presence of hepatic NRH or vascular thrombosis in children, we recommend that APS be differentially diagnosed using lupus anticoagulant and aCL and appropriate management be implemented.
Leukocytes infiltration correlates intratumoral microvessel density and influence overall and late-phase disease-free survival in hepatocellular carcinoma
Authors: Yang Yuan , Fu Ning , Wang Haiqing , Hao Jingcheng
Published: December 2021

Hepatocellular carcinoma (HCC) is a severe type of primary liver cancer with high postoperative recurrence. The prognosis predictability of tumor-infiltrating leukocytes (TILs) for patients who underwent HCC resection has been widely reported. However, limited information is available about TIL trafficking, which is also crucial for HCC patients.

We included tumor tissue samples and clinical data from 89 HCC patients in this study and performed immunohistochemistry for CD3, CD8, FoxP3, and CD31. TILs were measured using an algorithm for quantification of tumor immune stroma (QTiS). Intratumoral microvessels were counted using Weidner's method. We first examined correlations among them and analyzed their relationships with clinical and survival data.

Intratumoral microvessel density (iMVD) was significantly correlated with infiltration of CD3+ (r = 0.338, P = .001) and CD8+ (r = 0.320, P = .002) cells, but not FoxP3+ (r = 0.153, P = .152) cells. After multivariate analysis, higher infiltration of CD3+ (P = .038) independently showed significant predictability on better overall survival after resection of HCC. Although no influence of CD3+ (P = .386) and CD8+ (P = .648) cells were found on general disease-free survival, infiltration of CD3+ (P = .012), tumor size (P = .032) and albumin (P = .007) cells independently predicted late-phase disease-free survival. No significant relationships regarding iMVD, and infiltration of FoxP3+ cells with overall and disease-free survival were found.

Our data suggest that increased iMVD could enrich tumor-infiltrating CD3+ cells. Infiltrated CD3+ cells could help to better predict both the overall and late-phase disease-free survival after resection of HCC.
Clinical characteristics and prognostic factors for Crohn’s disease relapses using natural language processing and machine learning: a pilot study
Authors: Gomollón Fernando , Gisbert Javier P. , Guerra Iván , Plaza Rocío , Pajares Villarroya Ramón , Moreno Almazán Luis , López Martín Mª Carmen , Domínguez Antonaya Mercedes , Vera Mendoza María Isabel , Aparicio Jesús , Martínez Vicente , Tagarro Ignacio , Fernández-Nistal Alonso , Lumbreras Sara , Maté Claudia , Montoto Carmen
Published: December 2021

Background

The impact of relapses on disease burden in Crohn’s disease (CD) warrants searching for predictive factors to anticipate relapses. This requires analysis of large datasets, including elusive free-text annotations from electronic health records. This study aims to describe clinical characteristics and treatment with biologics of CD patients and generate a data-driven predictive model for relapse using natural language processing (NLP) and machine learning (ML).

Methods

We performed a multicenter, retrospective study using a previously validated corpus of CD patient data from eight hospitals of the Spanish National Healthcare Network from 1 January 2014 to 31 December 2018 using NLP. Predictive models were created with ML algorithms, namely, logistic regression, decision trees, and random forests.

Results

CD phenotype, analyzed in 5938 CD patients, was predominantly inflammatory, and tobacco smoking appeared as a risk factor, confirming previous clinical studies. We also documented treatments, treatment switches, and time to discontinuation in biologics-treated CD patients. We found correlations between CD and patient family history of gastrointestinal neoplasms. Our predictive model ranked 25 000 variables for their potential as risk factors for CD relapse. Of highest relative importance were past relapses and patients’ age, as well as leukocyte, hemoglobin, and fibrinogen levels.

Conclusion

Through NLP, we identified variables such as smoking as a risk factor and described treatment patterns with biologics in CD patients. CD relapse prediction highlighted the importance of patients’ age and some biochemistry values, though it proved highly challenging and merits the assessment of risk factors for relapse in a clinical setting.
Emulsifiers and Intestinal Health
Authors: Richey Levine Arielle , Picoraro Joseph A. , Dorfzaun Sally , LeLeiko Neal S.
Published: December 2021

Food additives in general, and emulsifiers in particular, are considered to be important dietary components with a potential to harm the intestine, in part by promoting intestinal inflammation. There is inadequate objective information about the specific nature and the magnitude of the problem.

The Food and Drug Administration (FDA) has recognized approximately 450 items added to our foods as being generally regarded as safe and has placed them on a generally regarded as safe (GRAS) list. Additionally, it has also approved approximately 3000 “food additives.” There is a general lack of transparency as to how either of these selections were and continue to be made. Once items are officially designated by the FDA as “food additives” or placed on the GRAS list, there is no regulatory mechanism for the ongoing monitoring of their safety.

The most widely used emulsifier is “lecithin,” which is biochemically identified as phosphatidylcholine (PC). Regulatory guidelines allow manufacturers to use the label “lecithin” to be applied to emulsifiers that contain PC plus other phospholipids in a variety of unspecified concentrations. The PC used in experiments cited in the literature, is unlikely to be the same thing as the “lecithin” in our diets.

The objective of this introduction to emulsifiers is to raise awareness of the current state of food additives in the USA and to encourage thoughtful approaches to the study of all additives found in our diets. The overriding goal should be to assure the safety of what we eat. As examples we discuss eight widely distributed food additives; four “natural” emulsifiers that are classified as GRAS as well as an additional emulsifier‐associated food additive that is also on the GRAS list, and three synthetic emulsifying agents that are FDA approved as “food additives.”
Interobserver and Intra-Observer Reliability of Eyelid Tests for Ocular Myasthenia Gravis
Authors: Jienmaneechotchai Thanchat , Apinyawasisuk Supanut , Jariyakosol Supharat , Hirunwiwatkul Parima
Published: December 2021

Background:

Lid fatigability test (LFT), Cogan lid twitch (CLT), and forced eyelids closure test (FECT) are simple clinical screening tests for ocular myasthenia gravis (OMG). However, these tests are subjectively interpreted. We thus evaluated the interobserver and intra-observer reliability of each test.

Methods:

The 3 eyelid tests were performed in ptotic patients associated with various conditions, including OMG and others. Video clips of all tests were recorded using smartphone with built-in camera in the following order; LFT, CLT, and FECT. All video clips were distributed to 3 neuro-ophthalmologists and 3 general ophthalmologists, who were trained to evaluate the tests using a single standard instruction. After 3 months, all video clips were re-organized for the second evaluation. Interobserver and intra-observer reliability were calculated using Cohens' Kappa coefficient and Fleiss Kappa statistic.

Results:

The 3 eyelid tests were performed and recorded in 35 patients, which included the diagnosis of OMG, levator muscle dehiscence, partial oculomotor nerve palsy, and Horner syndrome. CLT received moderate-to-substantial interobserver reliability in neuro-ophthalmologist group (Fleiss Kappa 0.77 [95% CI 0.60–0.94] and 0.66 [95% CI 0.46–0.85] in first and second evaluation respectively), but the results varied in general ophthalmologist group (Fleiss Kappa 0.58 [95% CI 0.37–0.79] and 0.54 [95% CI 0.33–0.76] in first and second evaluation respectively). FECT and LFT received lower interobserver reliability in both groups. CLT also received moderate-to-almost perfect intra-observer reliability in neuro-ophthalmologist group (Cohen Kappa 0.55, 0.58, and 0.92), whereas FECT and LFT received lower intra-observer reliability. The intra-observer reliability varied among general ophthalmologists for all 3 eyelid tests.

Conclusions:

CLT is the most reliable test among the 3 eyelid tests. However, all tests should be interpreted with caution by general ophthalmologists.
Hemisphere-Dependent Ictal Tachycardia Versus Ictal Bradycardia in a Critically Ill Patient
Authors: Fong Michael W. K. , Norris Sarah , Percy Jennifer , Hirsch Lawrence J. , Herlopian Aline
Published: December 2021

Tachycardia is a common ictal phenomenon; however, ictal bradycardia is less commonly reported and rarely presents as ictal asystole/syncope. In critically ill patients, seizures are much less likely to manifest with overt clinical signs, i.e., are more likely to be subtle or nonconvulsive. In this setting, changes in heart rate may be the only clue that seizures are occurring. The authors report an exemplary case of a 78-year-old right-handed man who presented with spontaneous left frontal intraparenchymal hemorrhages. During standard clinical monitoring in the Neuro-Intensive Care Unit, the patient had discrete paroxysms of relative sinus tachycardia, independent episodes of sinus bradycardia, and 3 to 4 seconds of sinus pause. The cardiac investigation was unrevealing, but continuous EEG revealed the answer. The episodes of mild tachycardia were associated with seizures from the left temporal region, whereas those with bradycardia were associated with independent seizures from the right temporal region. The case stands as a stark reminder to remain vigilant of seizures in high-risk patients, especially as a cause for paroxysmal autonomic changes.
Looking through the FOG: microbiome characterization and lipolytic bacteria isolation from a fatberg site
Authors: Court Elizabeth K. , Chaudhuri Roy R. , Kapoore Rahul V. , Villa Raffaella X. , Pandhal Jagroop , Biggs Catherine A. , Stafford Graham P.
Published: December 2021

Sewer systems are complex physical, chemical and microbial ecosystems where fats, oils and grease (FOG) present a major problem for sewer management. Their accumulation can lead to blockages (‘Fatbergs’), sewer overflows and disruption of downstream wastewater treatment. Further advancements of biological FOG treatments need to be tailored to degrade the FOG, and operate successfully within the sewer environment. In this study we developed a pipeline for isolation of lipolytic strains directly from two FOG blockage sites in the UK, and isolated a range of highly lipolytic bacteria. We selected the five most lipolytic strains using Rhodamine B agar plates and pNP-Fatty acid substrates, with two

Serratia

spp., two

Klebsiella

spp. and an environmental

Acinetobacter

strain that all have the capacity to grow on FOG-based carbon sources. Their genome sequences identified the genetic capacity for fatty acid harvesting (lipases), catabolism and utilization (Fad genes). Furthermore, we performed a preliminary molecular characterization of the microbial community at these sites, showing a diverse community of environmental bacteria at each site, but which did include evidence of sequences related to our isolates. This study provides proof of concept to isolation strategies targeting Fatberg sites to yield candidate strains with bioremediation potential for FOG in the wastewater network. Our work sets the foundation for development of novel bioadditions tailored to the environment with non-pathogenic

Acinetobacter

identified as a candidate for this purpose.
miR2Trait: an integrated resource for investigating miRNA-disease associations
Authors: Babu Poornima , Palaniappan Ashok
Published: December 2021

MicroRNAs are key components of cellular regulatory networks, and breakdown in miRNA function could lead to cascading effects culminating in pathophenotypes. A better understanding of the role of miRNAs in diseases would aid human health. Here, we have devised a method for comprehensively mapping the associations between miRNAs and diseases by merging on a common key between two curated omics databases. The resulting bidirectional resource, miR2Trait, is more detailed than earlier catalogues, uncovers new relationships, and includes analytical utilities to interrogate and extract knowledge from these datasets. The resource could aid in identifying the disease enrichment of a user-given set of miRNAs and analyzing the miRNA profile of a specified diseasome. miR2Trait is available as both a web-server (https://sas.sastra.edu/pymir18) and an open-source command-line interface (https://github.com/miR2Trait) under MIT license for both commercial and non-commercial use. The datasets are available for download at: https://doi.org/10.6084/m9.figshare.8288825.
Crowding changes appearance systematically in peripheral, amblyopic, and developing vision
Authors: Kalpadakis-Smith A.V. , Tailor V.K. , Dahlmann-Noor A.H. , Greenwood J.A.
Published: December 2021

Visual crowding is the disruptive effect of clutter on object recognition. Although most prominent in adult peripheral vision, crowding also disrupts foveal vision in typically-developing children and those with strabismic amblyopia. Do these crowding effects share the same mechanism? Here we exploit observations that crowded errors in peripheral vision are not random: target objects appear either averaged with the flankers (assimilation), or replaced by them (substitution). If amblyopic and developmental crowding share the same mechanism then their errors should be similarly systematic. We tested foveal vision in children aged 3-8 years with typical vision or strabismic amblyopia, and peripheral vision in typical adults. The perceptual effects of crowding were measured by requiring observers to adjust a reference stimulus to match the perceived orientation of a target ‘Vac-Man’ element. When the target was surrounded by flankers that differed by ±30°, all three groups (adults and children with typical or amblyopic vision) reported orientations between the target and flankers (assimilation). Errors were reduced with ±90° differences, but primarily matched the flanker orientation (substitution) when they did occur. A population pooling model of crowding successfully simulated this pattern of errors in all three groups. We conclude that the perceptual effects of amblyopic and developing crowding are systematic and resemble the near periphery in adults, suggesting a common underlying mechanism.

Precis

Crowding strongly disrupts peripheral vision, as well as the foveal vision of children with typical vision and amblyopia. We show that typically developing and amblyopic children make the same crowded errors as adults in the visual periphery, consistent with a common mechanism in all three cases.
Medical Students’ Perceptions of Learning and Working on the COVID-19 Frontlines: “… a confirmation that I am in the right place professionally.”
Authors: Klasen Jennifer M. , Schoenbaechler Zoe , Bogie Bryce , Meienberg Andrea , Nickel Christian , Bingisser Roland , LaDonna Kori
Published: December 2021

Introduction

The COVID-19 pandemic caused complex and enduring challenges for health care providers and medical educators and changed the medical education landscape for learners. Medical students were required to adapt and learn in a novel learning environment while universities paused their formal medical training. The current study sought to investigate medical students’ experiences working on a pandemic frontline to understand how they perceived this novel learning environment influenced both their learning and their developing professional identity.

Methods

We conducted semi-structured interviews with 21 medical students who worked in a COVID-19 testing facility at the University Hospital of Basel. Using constructivist grounded theory methodology, we collected and analyzed data iteratively using a constant comparative approach to develop codes and theoretical categories.

Results

Participants described improvements in their technical and communication skills, consequently impacting their professional development. The presence of a perceived flat hierarchy between the physicians and medical students promoted professional identity development amongst the medical students. Most participants perceived working on the pandemic frontlines as a positive learning experience, which seemed supported by a flatter hierarchy and open communication compared to their usual learning environment.

Conclusion

Since medical students reported that their work on the pandemic frontlines positively affected their learning, the need to create hands-on learning opportunities for medical students challenge curriculum developers. Medical students wish to feel like full-fledged care team members rather than observing learners. Performing simple clinical tasks and collaborative moments in a supportive learning environment may promote learning and professional development.
Draft genome of the Brazilian railroad worm Phrixothrix hirtus E.Olivier (Phengodidae: Coleoptera)
Authors: Amaral Danilo Trabuco , Mitani Yasuo , Silva Bonatelli Isabel Aparecida , Cerri Ricardo , Ohmiya Yoshihiro , Viviani Vadim
Published: December 2021

The Neotropical region is the richest in bioluminescent Coleoptera species, however, its bioluminescence megadiversity is still underexplored in terms of genomic organization and evolution, mainly within the Phengodidae family. The railroad worm Phrixothrix hirtus is an important biological model and symbolic species due to its bicolor bioluminescence, being the only organism that produces true red light among bioluminescent terrestrial species. Here, we performed the partial genome assembly of P. hirtus, combining short and long reads generated with Illumina sequencing, providing an important source of genomic information and a framework for comparative genomic analyses for the evaluation of the bioluminescent system in Elateroidea. The estimated genome size has ∼3.4Gb, 32% of GC content, and 67% of repetitive elements, being the largest genome described in the Elateroidea superfamily. Several events of gene family expansions associated with anatomical development and morphogenesis, as well as distinct odorant-binding receptors and retrotransposable elements were found in this genome. Similar molecular functions and biological processes are shared with other studied species of Elateriformia. Common genes putatively associated with bioluminescence production and control, including two luciferase genes that displayed 7 exons and 6 introns, and genes that could be involved in luciferin biosynthesis were found, indicating that there are no clear differences about the presence or absence of gene families associated with bioluminescence in Elateroidea. In P. hirtus the conversion of L- to D-luciferin seems to involve additional steps using a Palmitoyl-CoA thioesterase instead of an Acyl-CoA synthetase, which was found in Lampyridae species.

Highlights

First draft genome assembly of Phengodidae, the largest one described in Coleoptera;

Gene family expansions associated with anatomical development and morphogenesis;

Bioluminescent control and luciferin biosynthesis genes are common within Elateroidea;

Despite similar bioluminescent system, metabolic routes may have evolved independently;
Mechanistic investigation of SARS-CoV-2 Omicron variant spike mutants via full quantum mechanical modeling
Authors: Zaccaria Marco , Genovese Luigi , Lawhorn Brigitte E. , Dawson William , Joyal Andrew S. , Hu Jingqing , Autissier Patrick , Nakajima Takahito , Johnson Welkin E. , Fofana Ismael , Farzan Michael , Momeni Babak
Published: December 2021

Ab initioquantum mechanical models can characterize and predict intermolecular binding, but only recently have models including more than a few hundred atoms gained traction. Here, we simulate ∼13,000 atoms to predict and characterize binding of SARS-CoV-2 spike variants to the human receptor ACE2 (hACE2). We compare four spike variants in our analysis: Wuhan, Omicron, and two Omicron-based variants. To assess binding, we mechanistically characterize the energetic contribution of each amino acid involved, and predict the effect of select single point mutations. We validate our computational predictions experimentally by comparing binding efficacy of spike variants to cells expressing hACE2. We argue that this computational model, QM-CR, can identify mutations critical for intermolecular interactions and inform the engineering of high-specificity interactors.

One-Sentence Summary

Ab initiomodeling can predict the strength of SARS-CoV-2 variants’ binding to human cell receptor.
No part gets left behind: Tiled nanopore sequencing of whole ASFV genomes stitched together using Lilo
Authors: Warr Amanda , Newman Caitlin , Craig Nicky , Vendelė Ingrida , Pilare Rizalee , Cruz Lilet Cariazo , Barangan Twinkle Galase , Morales Reildrin G , Opriessnig Tanja , Venturina Virginia Mauro , Mananggit Milagros R , Lycett Samantha , Domingo Clarissa YJ , Tait-Burkard Christine
Published: December 2021

African Swine Fever virus (ASFV) is the causative agent of a deadly, panzootic disease, infecting wild and domesticated suid populations. Contained for a long time to the African continent, an outbreak of a particularly infectious variant in Georgia in 2007 initiated the spread of the virus around the globe, severely impacting pork production and local economies. The virus is highly contagious and has a mortality of up to 100% in domestic pigs. It is critical to track the spread of the virus, detect variants associated with pathology, and implement biosecurity measures in the most effective way to limit its spread. Due to its size and other limitations, the 170-190kbp large DNA virus has not been well sequenced with fewer than 200 genome sequences available in public repositories. Here we present an efficient, low-cost method of sequencing ASFV at scale. The method uses tiled PCR amplification of the virus to achieve greater coverage, multiplexability and accuracy on a portable sequencer than achievable using shotgun sequencing. We also present Lilo, a pipeline for assembling tiled amplicon data from viral or microbial genomes without relying on polishing against a reference, allowing for structural variation and hypervariable region assembly other methods fail on. The resulting ASFV genomes are near complete, lacking only parts of the highly repetitive 3’- and 5’telomeric regions, and have a high level of accuracy. Our results will allow sequencing of ASFV at optimal efficiency and high throughput to monitor and act on the spread of the virus.
Moving Beyond Processing and Analysis-Related Variation in Neuroscience
Authors: Li Xinhui , Esper Nathalia Bianchini , Ai Lei , Giavasis Steve , Jin Hecheng , Feczko Eric , Xu Ting , Clucas Jon , Franco Alexandre , Heinsfeld Anibal Sólon , Adebimpe Azeez , Vogelstein Joshua T. , Yan Chao-Gan , Esteban Oscar , Poldrack Russell A. , Craddock Cameron , Fair Damien , Satterthwaite Theodore , Kiar Gregory , Milham Michael P.
Published: December 2021

When fields lack consensus standard methods and accessible ground truths, reproducibility can be more of an ideal than a reality. Such has been the case for functional neuroimaging, where there exists a sprawling space of tools and processing pipelines. We provide a critical evaluation of the impact of differences across five independently developed minimal preprocessing pipelines for functional MRI. We show that even when handling identical data, inter-pipeline agreement was only moderate, critically shedding light on a factor that limits cross-study reproducibility. We show that low inter-pipeline agreement mainly becomes appreciable when the reliability of the underlying data is high, which is increasingly the case as the field progresses. Crucially, we show that when inter-pipeline agreement is compromised, so too are the consistency of insights from brainwide association studies. We highlight the importance of comparing analytic configurations, as both widely discussed and commonly overlooked decisions can lead to marked variation.
A framework for defining livestock ecotypes based on ecological modelling and exploring genomic environmental adaptation: the example of Ethiopian village chicken
Authors: Vallejo-Trujillo Adriana , Kebede Adebabay , Lozano-Jaramillo Maria , Dessie Tadelle , Smith Jacqueline , Hanotte Olivier , Gheyas Almas
Published: December 2021

In evolutionary ecology, an ecotype is a population that is genetically adapted to specific environmental conditions. Environmental and genetic characterisation of livestock ecotypes can play a crucial role in conservation and breeding improvement, particularly to achieve climate resilience. However, livestock ecotypes are often arbitrarily defined without a detailed characterisation of their agro-ecologies. In this study, we employ a novel integrated approach, combining Ecological Niche Modelling (ENM) with genomics, to delineate ecotypes based on environmental characterisation of population habitats and unravel the signatures of adaptive selection in the ecotype genomes. The method was applied on 25 Ethiopian village chicken populations representing diverse agro-climatic conditions. ENM identified six key environmental drivers of adaptation and delineated 12 ecotypes. Within- ecotype selection signature analyses (using Hp and iHS methods) identified 1,056 candidate sweep regions (SRs) associated with diverse biological processes. A few biological pathways were shared amongst most ecotypes and the involved genes showed functions important for scavenging chickens, e.g. neuronal development/processes, immune response, vision development, and learning. Genotype-environment association using Redundancy Analysis (RDA) allowed for correlating ∼33% of the SRs with major environmental drivers. Inspection of some strong candidate genes from selection signature analysis and RDA showed highly relevant functions in relation to the major environmental drivers of corresponding ecotypes. This integrated approach offers a powerful tool to gain insight into the complex processes of adaptive evolution including the genotype x environment (GxE) interactions.
Efficiently, accurately, intelligently dissecting bamboo: characteristic of vascular bundle in Phyllostachys
Authors: Xu Haocheng , Zhang Ying , Wang Jiajun , Zhong Tuhua , Ma Xinxin , Li Jing , Wang Hankun
Published: December 2021

A comprehensive understanding of vascular bundles is the key to elucidate the excellent intrinsic mechanical properties of bamboo. This research aims to investigate the gradient distribution of fiber volume fraction and the gradient changes in the shape of vascular bundles along the radial axis in Phyllostachys. We constructed a universal transfer-learning-based vascular bundle detection model with high precision of up to 96.97%, which can help to acquire the characteristics of vascular bundles quickly and accurately. The total number of vascular bundles, total fiber sheath area, the length, width and area of fiber sheath of individual vascular bundles within the entire cross-section were counted, and the results showed that these parameters had a strongly positive linear correlation with the outer circumference and wall thickness of bamboo culms, but the fiber volume fraction (around 25.5 %) and the length-to-width ratio of the vascular bundles (around 1.226) were relatively constant. Furthermore, we layered the cross section of bamboo according to the wall thickness finely and counted the characteristics of vascular bundle in each layer. The results showed that the radial distribution of fiber volume fraction decreased exponentially, the radial distribution of the length-to-width ratio of vascular bundle decreased quadratically, the radial distribution of the width of vascular bundle increased linearly. The trends of the gradient change in vascular bundle’s characteristics were found highly consistent among 29 bamboo species in Phyllostachys.

One sentence summary

A universal vascular bundle detection model can efficiently dissect vascular bundles in Phyllostachys, and the radial gradient change of vascular bundles in cross-section are found highly consistent.
Combining deep learning and automated feature extraction to analyze minirhizotron images: development and validation of a new pipeline
Authors: Bauer Felix M. , Lärm Lena , Morandage Shehan , Lobet Guillaume , Vanderborght Jan , Vereecken Harry , Schnepf Andrea
Published: December 2021

Root systems of crops play a significant role in agro-ecosystems. The root system is essential for water and nutrient uptake, plant stability, symbiosis with microbes and a good soil structure. Minirhizotrons, consisting of transparent tubes that create windows into the soil, have shown to be effective to non-invasively investigate the root system. Root traits, like root length observed around the tubes of minirhizotron, can therefore be obtained throughout the crop growing season. Analyzing datasets from minirhizotrons using common manual annotation methods, with conventional software tools, are time consuming and labor intensive. Therefore, an objective method for high throughput image analysis that provides data for field root-phenotyping is necessary. In this study we developed a pipeline combining state-of-the-art software tools, using deep neural networks and automated feature extraction. This pipeline consists of two major components and was applied to large root image datasets from minirhizotrons. First, a segmentation by a neural network model, trained with a small image sample is performed. Training and segmentation are done using “Root-Painter”. Then, an automated feature extraction from the segments is carried out by “RhizoVision Explorer”. To validate the results of our automated analysis pipeline, a comparison of root length between manually annotated and automatically processed data was realized with more than 58,000 images. Mainly the results show a high correlation (R=0.81) between manually and automatically determined root lengths. With respect to the processing time, our new pipeline outperforms manual annotation by 98.1 - 99.6 %. Our pipeline,combining state-of-the-art software tools, significantly reduces the processing time for minirhizotron images. Thus, image analysis is no longer the bottle-neck in high-throughput phenotyping approaches.
Foundation Model Enables Interpretable Open and Error-Tolerant Searching for Mass Spectrometry-Based Proteomics
Authors: Altenburg Tom , Muth Thilo , van Zalm Patrick , Steen Hanno , Renard Bernhard Y.
Published: December 2021

Mass spectrometry-based proteomics allows to study all proteins of a sample on a molecular level. However, mass spectra are noisy and contain complex patterns, making them inherently challenging to analyze with purely algorithmic approaches. In terms of the protein sequence landscape, most recent bottom-up MS-based proteomics studies consider either a diverse pool of post-translational modifications, employ large databases – as in metaproteomics or proteogenomics, study multiple isoforms of proteins, include unspecific cleavage sites or even combinations thereof. All this makes peptide and protein identifications challenging due to sheer size of the search space. To cope with this two-sided challenge, i.e. the complexity of real spectra and the search space size, we present a foundation model, called yHydra, that jointly embeds spectra and peptides. This allows us to implement various downstream tasks and search modes in Euclidean space. In particular, we implement an open search which allows to query multiple ten-thousands of spectra against millions of peptides. Furthermore, we implement an error-tolerant search for identifying additional proteoforms that are not included in off-the-shelf reference proteomes. Our foundation model provides meaningful embeddings, as we interpret learned peptide embeddings in comparison to the peptide’s physico-chemical properties. yHydra’s open search, assigns delta masses to each identification which allows to unrestrictedly characterize post-translational modifications. The error-tolerant mode of yHydra can be used as post-processing to existing search engines or as a standalone. yHydra is evaluated on several real life data sets for the identification of modified protein sequences and shows up to 25% increase in protein identification at constant false discovery rate compared to the current state-of-the-art.

Availability

(under MIT license)https://gitlab.com/dacs-hpi/yHydra

Contact

bernhard.renard@hpi.de
The SPICA Coarse-Grained Force Field for Proteins and Peptides
Authors: Kawamoto Shuhei , Liu Huihui , Seo Sangjae , Miyazaki Yusuke , Dixit Mayank , DeVane Russell , MacDermaid Christopher , Fiorin Giacomo , Klein Michael L. , Shinoda Wataru
Published: December 2021

A coarse-grained (CG) model for peptides and proteins was developed as an extension of the SPICA (Surface Property fItting Coarse grAined) force field (FF). The model was designed to examine membrane proteins that are fully compatible with the lipid membranes of the SPICA FF. A preliminary version of this protein model was created using thermodynamic properties, including the surface tension and density in the SPICA (formerly called SDK) FF. In this study, we improved the CG protein model to facilitate molecular dynamics (MD) simulation with a reproduction of multiple properties from both experiments and all-atom (AA) simulations. The side chain analogs reproduced the transfer free energy profiles across the lipid membrane and demonstrated reasonable dimerization free energies in water compared to those from AA-MD. A series of peptides/proteins adsorbed or penetrated into the membrane simulated by the CG-MD correctly predicted the penetration depths and tilt angles of peripheral and transmembrane peptides/proteins comparable to those in the orientation of protein in membrane (OPM) database. In addition, the dimerization free energies of several transmembrane helices within a lipid bilayer were comparable to those from experimental estimation. Application studies on a series of membrane protein assemblies, scramblases, and poliovirus capsids demonstrated a good performance of the SPICA FF.
Redox-active secondary metabolites act as interspecies modulators of antibiotic resilience
Authors: Meirelles Lucas A. , Newman Dianne K.
Published: December 2021

Bacterial opportunistic pathogens make a wide range of secondary metabolites both in the natural environment and when causing infections, yet how these molecules mediate microbial interactions and their consequences for antibiotic treatment are still poorly understood. Here, we explore the role of two redox-active secondary metabolites, pyocyanin and toxoflavin, as interspecies modulators of antibiotic resilience. We find that these molecules dramatically change susceptibility levels of diverse bacteria to clinical antibiotics. Pyocyanin is made by Pseudomonas aeruginosa, while toxoflavin is made by Burkholderia gladioli, organisms that infect cystic fibrosis and other immunocompromised patients. Both molecules alter the susceptibility profile of pathogenic species within the “Burkholderia cepacia complex” to different antibiotics, either antagonizing or potentiating their effects, depending on the drug’s class. Defense responses regulated by the redox-sensitive transcription factor SoxR potentiate the antagonistic effects these metabolites have against fluoroquinolones, and the presence of genes encoding SoxR and the efflux systems it regulates can be used to predict how these metabolites will affect antibiotic susceptibility of different bacteria. Finally, we demonstrate that inclusion of secondary metabolites in standard protocols used to assess antibiotic resistance can dramatically alter the results, motivating the development of new tests for more accurate clinical assessment.
Serum Amyloid A promotes Acetaminophen-induced liver injury by damaging sinusoidal endothelial cell and exacerbating platelet aggregation in liver
Authors: You Kai , Wang Yan , Chen Xiaoxia , Yang Zhen , Chen Yan , Tan Shenglin , Tao Jiawang , Getachew Anteneh , Pan Tingcai , Xu Yingying , Zhuang Yuanqi , Yang Fan , Lin Xianhua , Li Yinxiong
Published: December 2021

Background

Acetaminophen (APAP) is the most commonly used non-prescription antipyretic and analgesic drugs. Overuse of APAP can cause hepatotoxicity. Liver sinusoidal endothelial cells (LSECs) damage is an important early event in APAP-induced liver injury. Serum amyloid A (SAA) is an acute phase protein that mainly produced by hepatocytes, and promotes endothelial dysfunction via a pro-inflammatory and pro-thrombotic effect in atherosclerosis and renal disease. However, the role of SAA in APAP-induced liver injury remains unclear.

Methods

In this study, we used neutralizing antibody (anti-SAA) or antagonistic small peptide derived from sequence of human SAA1/2 (SAA-pep) to block the functional activity of Saa1/2 in mouse serum. Immunohistochemistry staining, Evans blue and platelet adhesion assays were performed to examine the liver damage, the integrity of sinusoidal endothelium and platelets accumulation in APAP-induce liver injury.

Results

Our study showed that in the early stage of APAP-induced acute liver injury in mice, the intrahepatic and serum Saa1/2 levels were significantly increased within 24 hours, and then gradually reduced to normal level from 3 days. Neutralization of Saa1/2 by antibodies or peptides effectively prevented the destruction of hepatic sinusoids, reduced the intrahepatic hemorrhage and platelet accumulation in liver, as well as increased the survival rate of mice treated with lethal dose of APAP. In vitro experiments showed that Saa1/2 aggravated LSECs death induced by APAP. Moreover, Saa1/2 promoted platelets adhesion on LSECs via Tlr2/Vcam-1 axis.

Conclusion

Our findings suggest that Saa1/2 promotes APAP-induced liver injury by damaged LSECs and exacerbated platelets aggregation. This study provides a potential target for intervention of acute liver injury/failure caused by hepatotoxic drugs such as APAP.
Bacterial community response to species overrepresentation or omission is strongly influenced by life in spatially structured habitats
Authors: Kleyer Hannah , Tecon Robin , Or Dani
Published: December 2021

Variations in type and strength of interspecific interactions in natural bacterial communities (e.g., synergistic to inhibitory) affect species composition and community functioning. The extent of interspecific interactions is often modulated by environmental factors that constrain diffusion pathways and cell mobility and limit community spatial arrangement. We studied how spatially structured habitats affect interspecific interactions and influence the resulting bacterial community composition. We used a bacterial community made of 11 well-characterized species that grew in porous habitats (comprised of glass beads) under controlled hydration conditions or in liquid habitats. We manipulated the initial community composition by overrepresenting or removing selected members, and observed community composition over time. Life in porous media reduced the number and strength of interspecific interactions compared to mixed liquid culture, likely due to spatial niche partitioning in porous habitats. The community converged to similar species composition irrespective of the initial species mix, however, the dominant bacterial species was markedly different between liquid culture and structured porous habitats. Moreover, differences in water saturation levels of the porous medium affected community assembly highlighting the need to account for habitat structure and physical conditions to better understand and interpret assembly of bacterial communities. We point at the modulation of bacterial interactions due to spatial structuring as a potential mechanism for promoting community stability and species coexistence, as observed in various natural environments such as soil or human gut.

Importance

Bacteria live as complex multispecies communities essential for healthy and functioning ecosystems ranging from soil to the human gut. The bacterial species that form these communities can have positive or negative impact on each other, promoting or inhibiting each other’s growth. Yet, the factors controlling the balance of such interactions in nature, and how these influence the community, are not fully understood. Here, we show that bacterial interactions are modified by life in spatially structured bacterial habitats. These conditions exert important control over the resulting bacterial community regardless of initial species composition. The study demonstrates limitations of inferences from bacterial communities grown in liquid culture relative to behaviour in structured natural habitats such as soil.