bluuebunny/crossref_metadata_2025 huggingface dataset:
Rarity of Pseudomonas agarici on Edible Mushrooms Associated with Susceptibility to Biological Competition
Authors: Moallem Mahsa , Hamidizade Mozhde , Taghavi S. Mohsen , Aeini Milad , Abachi Hamid , Haghighi Shahrad , Soleimani Ardavan , Hockett Kevin L. , Bull Carolee T. , Osdaghi Ebrahim
Published: April 2024

Taxonomically diverse Pseudomonas species induce bacterial blotch of edible mushrooms around the world. Pseudomonas tolaasii, [P. gingeri], and P. agarici are dominant mycopathogenic pseudomonads in mushroom production farms. In this study, among 216 mycopathogenic bacterial strains isolated from edible mushrooms in Iran, 96 strains were identified as Pseudomonas spp., while only three strains were preliminarily identified as P. agarici. Multilocus sequence analysis showed that only one strain (FH2) authentically belonged to P. agarici, while the other two strains either belonged to [P. gingeri] or represented a unique phylogenetic clade. The three strains also differed from each other in phenotypic characteristics, for example, production of fluorescent pigment and the reaction to tolaasin produced by P. tolaasii. Pathogenicity assays under a controlled environment showed that the symptoms induced by authentic P. agarici were far less severe than those caused by the predominant species P. tolaasii. Furthermore, coinoculation of P. agarici with three bacterial pathogens that are prevalent in Iran on mushroom caps, that is, P. tolaasii, Ewingella americana, and Mycetocola sp., resulted in the development of combined symptoms representing characteristics of both pathogens. The antibiosis assay showed that tolaasin-producing strains of P. tolaasii could inhibit the growth of P. agarici, while tolaasin-negative strains of the same species were unable to do so. This led us to the hypothesis that the inhibitory effect of P. tolaasii on P. agarici is driven by tolaasin production in the former species. This inhibitory effect is also associated with the rarity of P. agarici in natural conditions.
Mitochondrial dynamics, quality control, and mtDNA in alcohol-associated liver disease and liver cancer
Authors: Ma Xiaowen , Niu Mengwei , Ni Hong-Min , Ding Wen-Xing
Published: April 2024

Mitochondria are intracellular organelles responsible for energy production, glucose and lipid metabolism, cell death, cell proliferation, and innate immune response. Mitochondria are highly dynamic organelles that constantly undergo fission, fusion, and intracellular trafficking, as well as degradation and biogenesis. Mitochondrial dysfunction has been implicated in a variety of chronic liver diseases including alcohol-associated liver disease, metabolic dysfunction–associated steatohepatitis, and HCC. In this review, we provide a detailed overview of mitochondrial dynamics, mitophagy, and mitochondrial DNA–mediated innate immune response, and how dysregulation of these mitochondrial processes affects the pathogenesis of alcohol-associated liver disease and HCC. Mitochondrial dynamics and mitochondrial DNA–mediated innate immune response may thereby represent an attractive therapeutic target for ameliorating alcohol-associated liver disease and alcohol-associated HCC.
A Case of Rapidly Progressive Proliferative Diabetic Retinopathy in the Setting of Severe Anorexia Nervosa
Authors: Arguinchona Lauren M , Caldwell Anne Strong , Gill Zafar S , Gange William , Le Christopher B , Mehta Nihaal , Marin Alejandro I , Manoharan Niranjan
Published: April 2024

Purpose:

To report a case of rapidly progressive diabetic retinopathy in the setting of admission for severe anorexia nervosa.

Methods:

Case report

Results:

A 21-year-old female with type 1 diabetes mellitus and mild nonproliferative diabetic retinopathy of both eyes was admitted for severe anorexia nervosa with a BMI of 12.5 and hemoglobin A1c of 10.6. Three months after admission, the patient reported visual complaints and was found to have severe nonproliferative diabetic retinopathy in the right eye and proliferative diabetic retinopathy with vitreous hemorrhage in the left eye. She was lost to follow-up for 4 months, then presented to clinic with bilateral proliferative diabetic retinopathy and a tractional retinal detachment of the right eye.

Conclusion:

There is a potential relationship between severe eating disorders and rapid worsening of diabetic retinopathy. Patients with type 1 diabetes who have acute complications due to eating disorders should be evaluated by an ophthalmologist to monitor for rapid progression of retinopathy.
An Analysis of Lesbian, Gay, Bisexual, Transgender, and Queer Curricula Inclusion: A National Study of Physician Assistant Programs
Authors: Jones Quinnette , Batchelder Heather , Sanchez Mara , Rolls Joanne
Published: April 2024

Introduction

The health professions education literature shows an increased focus on inclusion of lesbian, gay, bisexual, transgender, and queer (LGBTQ) content in curricula; however, it does not address hours of content or methods for content delivery. The purpose of this study was to describe the delivery of LGBTQ content in physician assistant (PA) education through a national survey of PA programs.

Methods

In 2021, a national program survey was sent to all US-accredited PA Programs (n = 284) and had a completion rate of 71.8% (n = 204). Descriptive statistics were conducted to describe trends and make comparisons in the delivery of LGBTQ content.

Results

Most PA programs are incorporating LGBTQ content into preclinical phases of PA education (81%) and describe that LGBTQ curricula align with institutional values (82%). Most report 1 to 3 hours of preclinical education for all LGBTQ population groups and cite medical interviewing courses as the most frequently used course to address LGTBQ care. Many programs (43%) do not provide instructional hours on LGBTQ content in the clinical phase, and the majority do not offer clinical rotations focused on this care. The results show variability in the level of preparedness that programs report on their students caring for LGBTQ populations.

Discussion

Physician assistant programs are generally integrating the content throughout their didactic curricula; however, few offer clinical experiences focused on caring for patients who are LGBTQ. Offering clinical experiences and assessing student competencies are areas of growth in health professions education as related to LGBTQ health.
Association of monocyte to HDL cholesterol ratio and a composite risk score with left ventricular aneurysm formation in patients with acute ST-segment elevation myocardial infarction
Authors: Ran Mengnian , Li Shiyang , Lan Jianjun , Chen Fengjuan , Wu Dengxuan
Published: April 2024

Background

Left ventricular aneurysm (LVA) is an important complication of acute myocardial infarction. This study aimed to investigate the potential predictive value of the monocyte count to high-density lipoprotein cholesterol ratio (MHR) and a composite risk score in determining the formation of LVA in patients with acute ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention.

Methods

We recruited 1005 consecutive patients with STEMI. Multivariable logistic regression analysis was conducted identify the independent risk factors for LVA formation. Predictive power of MHR and composite risk score for LVA formation were assessed using receiver operating characteristic curve analysis.

Results

The MHR was significantly higher among patients with LVA compared to those without LVA [6.6 (3.8–10.8) vs. 4.6 (3.3–6.3), P < 0.001]. Univariable logistic regression analysis revealed that MHR (OR = 3.866, 95% CI = 2.677–5.582, P < 0.001) was associated with the risk of LVA formation. The predictive value of MHR remained significant even after multivariate logistic regression analysis [odds ratio (OR) = 4.801, 95% confidence interval (CI) = 2.672–8.629, P < 0.001]. The discriminant power of MHR for LVA is 0.712, which is superior to both monocyte (C statistic = 0.553) and high-density lipoprotein cholesterol (C statistic = 0.654). The composite risk score including MHR, gender, LVEF, hemoglobin, lymphocyte and left anterior descending artery as the culprit vessel could significantly increase the predictive ability (C statistic = 0.920).

Conclusion

A higher MHR could effectively identify individuals at high risk of LVA formation, especially when combined with gender, LVEF, hemoglobin, lymphocyte and left anterior descending artery as the culprit vessel.
Management of dyslipidemia in coronary artery disease: the present and the future
Authors: Dimitriadis Kyriakos , Theofilis Panagiotis , Iliakis Panagiotis , Pyrpyris Nikolaos , Dri Eirini , Sakalidis Athanasios , Soulaidopoulos Stergios , Tsioufis Panagiotis , Fragkoulis Christos , Chrysohoou Christina , Tsiachris Dimitrios , Tsioufis Konstantinos
Published: April 2024

Coronary artery disease (CAD) remains a leading cause of global morbidity and mortality, necessitating continuous refinement in the management of dyslipidemia, one of its major risk factors, to mitigate cardiovascular risks. Previous studies have proven the critical role of immediate and robust low-density lipoprotein cholesterol (LDL-C) reduction in the aftermath of acute coronary syndrome (ACS). Emphasizing the evidence supporting this approach, we delve into the impact of early intervention on cardiovascular outcomes and propose optimal strategies for achieving rapid LDL-C lowering, while also providing the rationale for early proprotein convertase subtilisin/kexin 9 inhibitor use after an ACS. Given the importance of the residual lipidemic risk, we present an overview of emerging therapeutic avenues poised to reshape dyslipidemia management, such as bempedoic acid, lipoprotein(a) inhibition, ApoC3 modulation, and angiopoietin-like protein 3 targeting. This comprehensive review amalgamates current evidence with future prospects, offering a holistic perspective on the management of dyslipidemia in CAD. By exploring both the urgency for immediate post-ACS LDL-C reduction and the exciting advancements on the horizon, this article provides a roadmap for clinicians navigating the intricate landscape of lipid-lowering therapies in CAD.
Efficacy and Safety of Gastric Per-Oral Endoscopic Myotomy (G-POEM)
Authors: Dolan Russell D. , McCarty Thomas R. , Bazarbashi Ahmad Najdat , Thompson Christopher C.
Published: April 2024

Background:

Gastric per-oral endoscopic myotomy (G-POEM) is an innovative treatment that has become increasingly utilized for patients with refractory gastroparesis. The aim of this systematic review and meta-analysis was to evaluate the safety and effectiveness of G-POEM for the treatment of gastroparesis.

Methods:

Individualized search strategies were developed through February 2021 in accordance with the PRISMA and MOOSE guidelines. This meta-analysis was performed by calculating pooled proportions and mean difference preprocedure and postprocedure with rates estimated using random effects models. Measured outcomes included technical success, clinical success, improvement in gastroparesis cardinal symptom index (GCSI), change in gastric emptying rate, alterations in impedance planimetry (functional lumen imaging probe [FLIP]) assessment, and adverse events.

Results:

A total of 20 studies (n=797 patients; 67.41% female) were included. The mean age was 48.92±11.61 y, with an average duration of 4.24±1.11 y since gastroparesis diagnosis. Technical success was 98.47% [(95% CI: 97.14, 99.19);I
2=0.00] with a mean myotomy length of 3.78±1.16 cm. In terms of clinical success, mean preprocedure GCSI scores were 3.38±0.37 and improved significantly postprocedure [weighted mean difference -1.56 (95% CI: −1.89 to −1.24); I
2=82.53; P<0.001]. Gastric retention after 4 hours demonstrated ~50% improvement (preprocedure 43.08±9.24% versus postprocedure 22.97±10.19%; P<0.001). FLIP assessment with 40 mL and 50 mL balloons demonstrated a significant increase in diameter, distensibility index, and cross-sectional area postprocedure (all P<0.05). Procedure-associated adverse events occurred among 10.92% [(95% CI 5.09 to 19.32); I
2=82.85] of patients.

Conclusion:

G-POEM appears safe and highly effective for the treatment of patients with refractory gastroparesis regardless of symptom predominance or etiology.
Body Compositions Correlate With Overt Hepatic Encephalopathy after Transjugular Intrahepatic Portosystemic Shunt
Authors: Shi Wenfeng , Xu Weiguo , Fan Ningning , Li Yong , Chen Xiaoqiong , Zhao Yujie , Bai Xiao , Yang Yang
Published: April 2024

Background:

The relationship between body composition and the risk of overt hepatic encephalopathy (OHE) following transjugular intrahepatic portosystemic shunt (TIPS) needs to be investigated.

Methods:

Overall, 571 patients from 5 medical centers were included. To assess body compositions, we evaluated skeletal muscle indices, adipose tissue indices, sarcopenia, and myosteatosis at the third lumbar vertebral level. Univariate and Multivariate logistic regression analyses were performed to identify independent risk factors for post-TIPS OHE. An integrated score was then constructed using stepwise multiple regression analyses, with a cut-off value selected using the best Youden index. Finally, the Akaike information criterion (AIC) was performed to compare the integrated score and independent risk factors on their ability in predicting post-TIPS OHE.

Results:

Sarcopenia and all skeletal muscle indices had limited associations with post-TIPS OHE. The index of the subcutaneous adipose tissue (SATI) (P=0.005; OR: 1.034, 95% CI: 1.010–1.058) and myosteatosis (297 cases, 52.01%, 125 with OHE, 42.09%; P=0.003; OR: 1.973; 95% CI: 1.262–3.084) were both ascertained as independent risk factors for post-TIPS OHE. The integrated score (ScoreALL=1.5760 + 0.0107 * SATI + 0.8579 * myosteatosis) was established with a cutoff value of −0.935. The akaike information criterion (AIC) of ScoreALL, SATI, and myosteatosis was 655.28, 691.18, and 686.60, respectively.

Conclusions:

SATI and myosteatosis are independent risk factors for post-TIPS OHE. However, the integrated score was more significantly associated with post-TIPS OHE than other skeletal muscle and adipose tissue factors.
My Partner Is My Family
Authors: Valenti Korijna , Doyon Katherine , Morgan Brianne , Quinn Gwendolyn , Bekelman David
Published: April 2024

In goals of care conversations and through the care trajectory, to avoid insensitive or discriminatory care, it is vital clinicians recognize lesbian, gay, bisexual, transgender, queer+ patients' values and wishes. In clinical settings, implicit bias operating within unconscious awareness may challenge the commitment to equitable care, negatively affecting patient outcomes. In this composite case, during a conversation with a social worker/nurse team, a cisgender woman repeatedly expressed her wishes for her female partner to be her decision maker instead of her biological family. The conversation stalled during the patient's attempts to identify her partner as her most valued and trusted person. Interviewer follow-up responses based on motivational interviewing techniques, which do not include strategies for lesbian, gay, bisexual, transgender, queer+ interactions, inaccurately reflected the patient's needs. Two ethical issues emerged, (1) autonomy and (2) beneficence. Clinicians should approach all patients using nongendered language, and allow patients to self-identify and decide which people are in their support system. Lack of inclusivity training has significant potential to affect the patient experience and decrease clinician/patient trust. Clinicians should not assume the decision maker is a cisgender, heterosexual partner or a biological family member. When patients speak about their partners, it is imperative clinicians use the patient's language and not avoid or redirect responses.
Improving Maternal Depression Screening in the Neonatal Intensive Care Unit
Authors: McCabe Jennifer E. , Henderson Lydia , Davila Rebecca Chuffo , Segre Lisa S.
Published: April 2024

Purpose:

To examine whether self-perceived benefits of mental health treatment differed between mothers of babies in the neonatal intensive care unit with and without a positive screen for depression based on their Edinburgh Postnatal Depression score.

Study Design and Methods:

Mothers were recruited in person pre-COVID-19 pandemic, and via phone call and online advertisement during the pandemic. Mothers completed a 10-item depression scale and whether they believed they would benefit from mental health treatment. A chi-square test determined the difference in perceived benefit between mothers who screened positively for depression and those who did not.

Results:

This secondary analysis included 205 mothers, with an average age of 29. Of the 68 mothers who screened positively for depression, 12 believed that would not benefit from mental health intervention. Of the 137 who screened negatively for depression, 18 believed they would benefit from mental health intervention. Mothers who screened negatively for depression were significantly less likely to believe they would benefit from mental health intervention.

Clinical Implications:

Depression screening scales offer guidance on which mothers to flag for follow-up, but neither on how a mother will respond nor how to effectively approach a mother about her mental health. Nurses can improve identification and follow-up of depressed mothers in the neonatal intensive care unit by asking mothers about their perceived need for mental health treatment.
In vivo assessment of human corneal epithelial cells in orthokeratology lens wearers: A pilot study
Authors: Pattan Hadiya F. , Liu Xiao , Tankam Patrice
Published: April 2024

SIGNIFICANCE

Central corneal epithelial thinning associated with midperipheral epithelial thickening has been reported as the main factor contributing to the effectiveness of orthokeratology (ortho-k) in myopia control. Yet, the cellular mechanism governing the regional change in refractive power remains elusive.

PURPOSE

This study aimed to evaluate the correlation between the regional change in corneal epithelial thickness and cell density in ortho-k wearers.

METHODS

A new human prototype of a polarization-dependent optical coherence microscope was developed to enable noncontact and noninvasive in vivo imaging of corneal epithelial cells in ortho-k wearers with and without their ortho-k lens. The epithelial thickness and cell density were evaluated at the central and midperipheral corneal locations in four ortho-k wearers and four spectacle wearers serving as controls.

RESULTS

Polarization-dependent optical coherence microscope achieved in vivo volumetric imaging of all epithelial cell types in ortho-k wearers with and without their lens over a field of view of 0.5 × 0.5 mm2 with an isotropic resolution of ~2.2 mm. The central epithelial thinning and midperipheral epithelial thickening were consistent across all ortho-k wearers. However, the inconsistency in their regional epithelial cell density highlighted a great variability in individual response to ortho-k treatment. There was no strong correlation between epithelial thickness and cell density, especially at the midperipheral cornea, in ortho-k participants.

CONCLUSIONS

This study constitutes our first step toward uncovering the cellular mechanism underlying the effectiveness of ortho-k in myopia control. Future studies will focus on the longitudinal evaluation of epithelial cells before and during ortho-k treatment to identify factors governing individual response to ortho-k treatment and ultimately inform the dynamics of epithelial cells taking place during the ortho-k treatment.
Case series: Superficial plexus en face may aid distinction of retinal nerve fiber layer loss from diabetic retinal ischemia versus glaucoma
Authors: Hynes Alex F. , Short Alaina M.
Published: April 2024

SIGNIFICANCE

In normal tension glaucoma suspects with diabetes, inspection of superficial plexus capillary dropout patterns on optical coherence tomography–angiography (OCT-A) may help differentiate retinal nerve fiber layer (RNFL) and ganglion cell loss due to retinal ischemia from glaucoma.

PURPOSE

This study aimed to demonstrate that the pattern and degree of capillary bed dropout in early glaucoma appear different on OCT-A superficial plexus en-face slabs compared with retinal ischemia. RNFL loss associated with retinal ischemia in diabetic patients may be explained and accounted for by overlying the RNFL deviation map on a superficial plexus en-face montage.

CASE REPORTS

Three middle-aged White men with diabetes mellitus showed cup-to-disc ratios of approximately 0.7 and RNFL and ganglion thinning. Each patient had several Cirrus OCT and OCT-A scans taken of the posterior pole. The OCT-A en-face images demonstrated specific patterns of superficial capillary dropout. The appearance of superficial plexus capillary dropout in one case of glaucoma is contrasted against two cases of retinal ischemia.

CONCLUSIONS

Early glaucoma appears to be associated with incomplete capillary bed dropout that extends from macular regions to the disc in a wedge- or arc-shaped pattern. Diabetic retinal ischemia appears to be associated with well-defined patchy and polygonal pockets of complete capillary bed obliteration that may not extend back to the disc. If an RNFL deviation map is superimposed over the superficial plexus en-face montage, areas of RNFL loss may correlate with and thus be well accounted for by areas of retinal ischemia in cases with RNFL thinning likely from ischemia. This approach may supplement inspection of OCT B-scans for focal retinal thinning when trying to differentiate RNFL and ganglion cell loss from retinal ischemia versus glaucoma in patients with diabetes. Formal research studies are needed to validate our observations and proposed use of OCT-A together with OCT in these patients.
Investigating the Link Between Subjective Depth Perception Deficits and Objective Stereoscopic Vision Deficits in Individuals With Acquired Brain Injury
Authors: Funayama Michitaka , Hojo Tomohito , Nakagawa Yoshitaka , Kurose Shin , Koreki Akihiro
Published: April 2024

Individuals with acquired brain injury have reported subjective complaints of depth perception deficits, but few have undergone objective assessments to confirm these deficits. As a result, the literature currently lacks reports detailing the correlation between subjective depth perception deficits and objective stereoscopic vision deficits in individuals with acquired brain injury, particularly those cases that are characterized by a clearly defined lesion. To investigate this relationship, we recruited three individuals with acquired brain injury who experienced depth perception deficits and related difficulties in their daily lives. We had them take neurologic, ophthalmological, and neuropsychological examinations. We also had them take two types of stereoscopic vision tests: a Howard-Dolman–type stereoscopic vision test and the Topcon New Objective Stereo Test. Then, we compared the results with those of two control groups: a group with damage to the right hemisphere of the brain and a group of healthy controls. Performance on the two stereoscopic vision tests was severely impaired in the three patients. One of the patients also presented with cerebral diplopia. We identified the potential neural basis of these deficits in the cuneus and the posterior section of the superior parietal lobule, which play a role in vergence fusion and are located in the caudal region of the dorso-dorsal visual pathway, which is known to be crucial not only for visual spatial perception, but also for reaching, grasping, and making hand postures in the further course of that pathway.
Staphylococcus aureus  associated with post-operative wound infections in Western Kenya reveals genomic hotspots for pathogen evolution

Authors: MOGOI NICHOLAS NYABERA , Sifuna Anthony Wawire , Okoth Patrick Kirsteen , Reva Oleg , Malaba Rose , Negesa Ruth , Nyongesa Peter Kuloba , Osoro Ezra Kombo , Welch Martin
Published: April 2024

Objectives.  Staphylococcus aureus is one of the most common pathogens attributed to hospital infections. Although S. aureus infections have been well studied in developed countries, far less is known about the biology of the pathogen in sub-Saharan Africa. 
Methods. Here, we report on the isolation, antibiotic resistance profiling, whole genome sequencing, and genome comparison of six multi-drug resistant isolates of S. aureus obtained from a referral hospital in Kakamega, Western Kenya.
Results. Five of the six isolates contained a 20.7-kb circular plasmid carrying blaZ (associated with resistance to b-lactam antibiotics). These five strains all belonged to the same sequence type, ST152. Despite the similarity of the plasmid these isolates, whole genome sequencing revealed that the strains differed, depending on whether they were associated with hospital-acquired or community-acquired infections.
Conclusion. The intriguing finding is that the hospital acquired and the community acquired isolates of S. aureusbelonging to the same genotype ST152 formed two separate sub-clusters in the phylogenetic tree and differed by the repertoire of accessory virulence genes suggesting an ongoing adaptive evolution and significant genomic plasticity.
Nanopore and Illumina sequencing reveal different viral populations from human gut samples
Authors: Cook Ryan , Telatin Andrea , Hsieh Shen-Yuan , Newberry Fiona , Tariq Mohammad A. , Baker Dave J. , Carding Simon R. , Adriaenssens Evelien M.
Published: April 2024

The advent of viral metagenomics, or viromics, has improved our knowledge and understanding of global viral diversity. High-throughput sequencing technologies enable explorations of the ecological roles, contributions to host metabolism, and the influence of viruses in various environments, including the human intestinal microbiome. However, bacterial metagenomic studies frequently have the advantage. The adoption of advanced technologies like long-read sequencing has the potential to be transformative in refining viromics and metagenomics. Here, we examined the effectiveness of long-read and hybrid sequencing by comparing Illumina short-read and Oxford Nanopore Technology (ONT) long-read sequencing technologies and different assembly strategies on recovering viral genomes from human faecal samples. Our findings showed that if a single sequencing technology is to be chosen for virome analysis, Illumina is preferable due to its superior ability to recover fully resolved viral genomes and minimise erroneous genomes. While ONT assemblies were effective in recovering viral diversity, the challenges related to input requirements and the necessity for amplification made it less ideal as a standalone solution. However, using a combined, hybrid approach enabled a more authentic representation of viral diversity to be obtained within samples.
Disentangling signal and noise in neural responses through generative modeling
Authors: Kay Kendrick , Prince Jacob S. , Gebhart Thomas , Tuckute Greta , Zhou Jingyang , Naselaris Thomas , Schutt Heiko
Published: April 2024

Measurements of neural responses to identically repeated experimental events often exhibit large amounts of variability. Thisnoiseis distinct fromsignal, operationally defined as the average expected response across repeated trials for each given event. Accurately distinguishing signal from noise is important, as each is a target that is worthy of study (many believe noise reflects important aspects of brain function) and it is important not to confuse one for the other. Here, we describe a principled modeling approach in which response measurements are explicitly modeled as the sum of samples from multivariate signal and noise distributions. In our proposed method—termed Generative Modeling of Signal and Noise (GSN)—the signal distribution is estimated by subtracting the estimated noise distribution from the estimated data distribution. Importantly, GSN improves estimates of the signal distribution, but does not provide improved estimates of responses to individual events. We validate GSN using ground-truth simulations and show that it compares favorably with related methods. We also demonstrate the application of GSN to empirical fMRI data to illustrate a simple consequence of GSN: by disentangling signal and noise components in neural responses, GSN denoises principal components analysis and improves estimates of dimensionality. We end by discussing other situations that may benefit from GSN’s characterization of signal and noise, such as estimation of noise ceilings for computational models of neural activity. A code toolbox for GSN is provided with both MATLAB and Python implementations.
A change in the cell wall status initiates the elimination of the nucellus in Arabidopsis
Authors: Xu Wenjia , Gomez-Paez Dennys-Marcela , Choinard Sandrine , Iannaccone Miryam , Maricchiolo Elisa , Peaucelle Alexis , Voxeur Aline , Haas Kalina T , Pompa Andrea , Magnani Enrico
Published: April 2024

The evolution of the seed habit coincides with a change in the cell fate of the nucellus, the sporophytic tissue responsible for female meiosis. Seeds arose when the nucellus retained the female spores instead of releasing them in the environment. As a consequence, the nucellus was partially eliminated to accommodate the growth of the female gametophyte inside the sporophyte. With the evolution of angiosperm seeds, the process of nucellus elimination was requisitioned to allow the growth of the endosperm, the second fertilization product devoted to store nutrients. Cell elimination differs from most known cell death programs as it leads to the apparent dismantling of the cell wall. Here, we show that nucellus elimination in Arabidopsis is initiated by the lysis of the pectic polysaccharides in the cell wall. This process exposes other cell wall components to possible further degradation and precedes a cell death program that leads to nuclear DNA fragmentation. Both pathways are regulated by TRANSPARENT TESTA 16, a MADS-domain transcription factor that evolved with seed plants. Finally, the causal effect of cell wall modification on nucellus development is demonstrated by inhibiting pectin degradation, thus suggesting that a change in the cell wall status might have driven seed evolution.
Characterizing Spatially Continuous Variations in Tissue Microenvironment through Niche Trajectory Analysis
Authors: Wang Wen , Zheng Shiwei , Shin Sujung Crystal , Yuan Guo-Cheng
Published: April 2024

Recent technological developments have made it possible to map the spatial organization of a tissue at the single-cell resolution. However, computational methods for analyzing spatially continuous variations in tissue microenvironment are still lacking. Here we present ONTraC as a strategy that constructs niche trajectories using a graph neural network-based modeling framework. Our benchmark analysis shows that ONTraC performs more favorably than existing methods for reconstructing spatial trajectories. Applications of ONTraC to public spatial transcriptomics datasets successfully recapitulated the underlying anatomical structure, and further enabled detection of tissue microenvironment-dependent changes in gene regulatory networks and cell-cell interaction activities during embryonic development. Taken together, ONTraC provides a useful and generally applicable tool for the systematic characterization of the structural and functional organization of tissue microenvironments.
Suitability of anthrax (Bacillus anthracis) in the Black Sea basin through the scope of distribution modelling
Authors: Arede Margarida , Allepuz Alberto , Beltran-Alcrudo Daniel , Casal Jordi , Romero-Alvarez Daniel
Published: April 2024

The Black Sea basin has a strategic geographical location bridging Asia and Europe and depends on traditional livestock practices. Anthrax, a zoonotic bacterial disease caused byBacillus anthracis, poses a significant global threat impacting public health, food security, pastoralist communities, and national economies. The disease is endemic or sporadic in the Black Sea basin, however, the study of its distribution has seldom been addressed, despite its burden and the presence of historicalB. anthracisburial sites in the region. The viability ofB. anthracisin a particular region is going to be influenced by multiple environmental factors, such as soil composition, climate, vegetation, and host abundance. To characterize the potential distribution ofB. anthracisin the Black Sea basin, and therefore, the potential for anthrax outbreaks, we applied an ecological niche modelling framework using the Maxent algorithm, analyzing multiple variable combinations, and proposing a novel approach for interpreting in-risk anthrax areas. Our findings underscored the importance of host abundance to the anthrax dynamics in the region. We identified anthrax-suitable areas spanning central and eastern Türkiye, Armenia, southern Georgia, southern Russia, Bulgaria, southern and eastern Romania, Hungary, Moldova, and southern Ukraine, which align with findings from previous global and regional studies on the potential suitability of anthrax. The insights gained from our research might facilitate the development of targeted interventions and policies to mitigate the spread of this disease in pastoralist communities in the Black Sea basin.
Mortality with concurrent treatment with gabapentin and opioids among people with spine diagnoses in the U.S. Medicare population: a propensity-matched cohort study
Authors: Gold Laura S , Heagerty Patrick J , Hansen Ryan N , Friedly Janna L , Johnston Sandra K , Deyo Richard A , Curatolo Michele , Turner Judith A , Rundell Sean D , Wysham Katherine , Jarvik Jeffrey G , Suri Pradeep
Published: April 2024

Importance: Given the negative impact of opioid use on population health, prescriptions for alternative pain-relieving medications, including gabapentin, have increased. Concurrent gabapentin and opioid prescriptions are commonly reported in retrospective studies of opioid-related overdose deaths. Objective: To determine whether people who filled gabapentin and opioid prescriptions concurrently ('gabapentin + opioids') had greater mortality than those who filled an active control medication (tricyclic antidepressants [TCAs] or duloxetine) and opioids concurrently ('TCAs/duloxetine + opioids'). We hypothesized that people treated with gabapentin + opioids would have higher mortality rates compared to people treated with TCAs/duloxetine + opioids. Design: Propensity score-matched cohort study with an incident user, active control design. The median (maximum) follow-up was 45 (1093) days. Setting: Population-based. Participants: Medicare beneficiaries with spine-related diagnoses 2017-2019. The primary analysis included those who concurrently (within 30 days) filled at least 1 incident gabapentin + at least 1 opioid or at least 1 incident TCA/duloxetine + at least 1 opioid. Exposures: People treated with gabapentin + opioids (n=67,133) were matched on demographic and clinical factors in a 1:1 ratio to people treated with TCAs/duloxetine + opioids (n=67,133). Main Outcomes and Measures: The primary outcome was mortality at any time. A secondary outcome was occurrence of a major medical complication at any time. Results: Among 134,266 participants (median age 73.4 years; 66.7% female), 2360 died before the end of follow-up. No difference in mortality was observed between groups (adjusted hazard ratio (HR) and 95% confidence interval (CI) for gabapentin + opioids was 0.98 (0.90, 1.06); p=0.63). However, people treated with gabapentin + opioids were at slightly increased risk of a major medical complication (1.02 (1.00, 1.04); p=0.03) compared to those treated with TCAs/duloxetine + opioids. Results were similar in analyses (a) restricted to less than or = 30-day follow-up and (b) that required at least 2 fills of each prescription. Conclusions and Relevance: When treating pain in older adults taking opioids, the addition of gabapentin did not increase mortality risk relative to addition of TCAs or duloxetine. However, providers should be cognizant of a small increased risk of major medical complications among opioid users initiating gabapentin compared to those initiating TCAs or duloxetine.
Electroconvulsive Therapy Modulates Loudness Dependence of Auditory Evoked Potentials: A Pilot MEG Study
Authors: Dib Michael , Lewine Jeffrey D. , Abbott Christopher C. , Deng Zhi-De
Published: April 2024

Electroconvulsive therapy (ECT) remains a critical intervention for treatment-resistant depression (MDD), yet its neurobiological underpinnings are not fully understood. This pilot study utilizes high-resolution magnetoencephalography (MEG) in nine depressed patients receiving right unilateral ECT, to investigate the changes in loudness dependence of auditory evoked potentials (LDAEP), a proposed biomarker of serotonergic activity, following ECT. We hypothesized that ECT would reduce the LDAEP slope, reflecting enhanced serotonergic neurotransmission. Contrary to this, our findings indicated a significant increase in LDAEP post-ECT (t8= 3.17,p= .013). The increase in LDAEP was not associated with changes in depression severity or cognitive performance, as assessed by the Hamilton Depression Rating Scale (HAMD-24) and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). We discussed potential mechanisms for the observed increase, including ECT’s impact on serotonergic, dopaminergic, glutamatergic, and GABAergic receptor activity, neuroplasticity involving brain-derived neurotrophic factor (BDNF), and inflammation modulators such as TNF-alpha. Our results suggest a complex interaction between ECT and these neurobiological systems, rather than a direct reflection of serotonergic neurotransmission.
State of the Interactomes: an evaluation of molecular networks for generating biological insights
Authors: Wright Sarah N. , Colton Scott , Schaffer Leah V. , Pillich Rudolf T. , Churas Christopher , Pratt Dexter , Ideker Trey
Published: April 2024

Advancements in genomic and proteomic technologies have powered the use of gene and protein networks (“interactomes”) for understanding genotype-phenotype translation. However, the proliferation of interactomes complicates the selection of networks for specific applications. Here, we present a comprehensive evaluation of 46 current human interactomes, encompassing protein-protein interactions as well as gene regulatory, signaling, colocalization, and genetic interaction networks. Our analysis shows that large composite networks such as HumanNet, STRING, and FunCoup are most effective for identifying disease genes, while smaller networks such as DIP and SIGNOR demonstrate strong interaction prediction performance. These findings provide a benchmark for interactomes across diverse network biology applications and clarify factors that influence network performance. Furthermore, our evaluation pipeline paves the way for continued assessment of emerging and updated interaction networks in the future.
High-resolution detection of copy number alterations in single cells with HiScanner
Authors: Zhao Yifan , Luquette Lovelace J , Veit Alexander D , Wang Xiaochen , Xi Ruibin , Viswanadham Vinayak V , Shao Diane D , Walsh Christopher A , Yang Hong Wei , Johnson Mark D , Park Peter J
Published: April 2024

Improvements in single-cell whole-genome sequencing (scWGS) assays have enabled detailed characterization of somatic copy number alterations (CNAs) at the single-cell level. Yet, current computational methods are mostly designed for detecting chromosome-scale changes in cancer samples with low sequencing coverage. Here, we introduce HiScanner (High-resolution Single-Cell Allelic copy Number callER), which combines read depth, B-allele frequency, and haplotype phasing to identify CNAs with high resolution. In simulated data, HiScanner consistently outperforms state-of-the-art methods across various CNA types and sizes. When applied to high-coverage scWGS data from human brain cells, HiScanner shows a superior ability to detect smaller CNAs, uncovering distinct CNA patterns between neurons and oligodendrocytes. For 179 cells we sequenced from longitudinal meningioma samples, integration of CNAs with point mutations revealed evolutionary trajectories of tumor cells. These findings show that HiScanner enables accurate characterization of frequency, clonality, and distribution of CNAs at the single-cell level in both non-neoplastic and neoplastic cells.
MIPDB: A maize image-phenotype database with multi-angle and multi-time characteristics
Authors: Wang Panpan , Chang Jianye , Deng Wenpeng , Liu Bingwen , Lai Haozheng , Hou Zhihao , Dong Linsen , Chen Qipian , Zhou Yun , Zhang Zhen , Liu Hailin , Ruan Jue
Published: April 2024

Plant phenomics has become one of the most significant scientific fields in recent years. However, typical phenotyping procedures have low accuracy, low throughput, and are labor-intensive and time-consuming. Large-scale phenotypic collection equipment, on the other hand, is pricy, rigid, and inconvenient. The advancement of phenomics has been hampered by these restrictions. Lightweight picture collection equipment can now be used to capture plant phenotypic data thanks to the development of deep learning-based image identification. For the purpose of training the model, this approach needs high-quality annotated datasets. In this study, we used a handheld camera to gather multi-angle, multi-time series images and an unmanned aerial vehicle (UAV) to create a maize image phenotyping database (MIPDB). Over 30,000 high-resolution photos are available in the MIPDB, with 17,631 of those images having been carefully tagged with point-line method. The MIPDB can be accessed by the general public athttp://phenomics.agis.org.cn. We anticipate that the availability of this superior dataset will stimulate a new revolution in crop breeding and advance deep learning-based phenomics research.
Marmosets as model systems for the study of Alzheimer’s disease and related dementias: substantiation of physiological Tau 3R and 4R isoform expression and phosphorylation
Authors: Huhe Hasi , Shapley Sarah M. , Duong Duc , Wu Fang , Ha Seung-Kwon , Choi Sang-Ho , Kofler Julia , Mou Yongshan , Guimaraes Thais Rafael , Thathiah Amantha , Schaeffer Lauren K.H. , Carter Gregory W. , Seyfried Nicholas T. , Silva Afonso C. , Sukoff Rizzo Stacey J.
Published: April 2024

INTRODUCTION

Marmosets have been shown to spontaneously develop pathological hallmarks of Alzheimer’s disease (AD) during advanced age, including amyloid-beta plaques, positioning them as a model system to overcome the rodent-to-human translational gap for AD. However, Tau expression in the marmoset brain has been understudied.

METHODS

To comprehensively investigate Tau isoform expression in marmosets, brain tissue from eight unrelated marmosets across various ages was evaluated and compared to human postmortem AD tissue. Microtubule-associated protein tau (MAPT) mRNA expression and splicing were confirmed by RT-PCR. Tau isoforms in the marmoset brain were examined by western blot, mass spectrometry, immunofluorescence, and immunohistochemical staining. Synaptic Tau expression was analyzed from crude synaptosome extractions.

RESULTS

3R and 4R Tau isoforms are expressed in marmoset brains at both transcript and protein levels across ages. Results from western blot analysis were confirmed by mass spectrometry, which revealed that Tau peptides in marmoset corresponded to the 3R and 4R peptides in the human AD brain. 3R Tau was primarily enriched in neonate brains, and 4R enhanced in adult and aged brains. Tau was widely distributed in neurons with localization in the soma and synaptic regions. Phosphorylation residues were observed on Thr-181, Thr-217, and Thr-231, Ser202/Thr205, Ser396/Ser404. Paired helical filament (PHF)-like aggregates were also detected in aged marmosets.

DISCUSSION

Our results confirm the expression of both 3R and 4R Tau isoforms and important phosphorylation residues in the marmoset brain. These data emphasize the significance of marmosets with natural expression of AD-related hallmarks as important translational models for the study of AD.
Laminar fMRI in the locked-in stage of amyotrophic lateral sclerosis shows preserved activity in layer Vb of primary motor cortex
Authors: Knudsen Lasse , Jespersen Bo , Heintzelmann Mia B. , Zhang Peng , Yang Yan , Lund Torben E. , Blicher Jakob U.
Published: April 2024

Amyotrophic lateral sclerosis (ALS) affects the cerebral cortex layer-dependently, most notably by the foremost targeting of upper motor neurons (UMNs) sited in layer Vb. Previous studies have shown a retained ability of paralysed patients to activate residual cortical motor networks, even in late-stage ALS. However, it is currently unknown whether such activation reflects a retained capacity to process sensorimotor inputs or if it is a result of actual motor output. Given the distinct function of individual cortical layers, layer-specific functional measurements may provide insight to this question. In this study, using submillimetre resolution laminar fMRI, we assessed the layer-dependent activation associated with attempted (motor) and passive (somatosensory) movements in a locked-in stage ALS patient. We found robust activation in both superficial and deep layers of primary motor cortex. The peak activation in deep layers was localised to layer Vb. These findings demonstrate preserved activity in deep output layers of M1, possibly reflecting a retained ability to engage residual UMNs despite years of paralysis. Our study underscores the capacity of laminar fMRI to discern subtle cortical activity and elucidates a promising pathway for probing in vivo human ALS pathology with unprecedented resolution.
Visualizing single-cell data with the neighbor embedding spectrum
Authors: Damrich Sebastian , Klockow Manuel V , Berens Philipp , Hamprecht Fred A , Kobak Dmitry
Published: April 2024

The two-dimensional embedding methods t-SNE and UMAP are ubiquitously used for visualizing single-cell data. Recent theoretical research in machine learning has shown that, despite their very different formulation and implementation, t-SNE and UMAP are closely connected, and a single parameter suffices to interpolate between them. This leads to a whole spectrum of visualization methods that focus on different aspects of the data. Along the spectrum, this focus changes from representing local structures to representing continuous ones. In single-cell context, this leads to a trade-off between highlighting rare cell types or continuous variation, such as developmental trajectories. Visualizing the entire spectrum as an animation can provide a more nuanced understanding of the high-dimensional dataset than individual visualizations with either t-SNE or UMAP.