bluuebunny/crossref_metadata_2025 huggingface dataset:
Simulation and implementation of two-layer oscillatory neural networks for image edge detection: bidirectional and feedforward architectures
Authors: Abernot Madeleine , Aida Todri-Sanial
Published: January 2023

The growing number of edge devices in everyday life generates a considerable amount of data that current AI algorithms, like artificial neural networks, cannot handle inside edge devices with limited bandwidth, memory, and energy available. Neuromorphic computing, with low-power oscillatory neural networks (ONNs), is an alternative and attractive solution to solve complex problems at the edge. However, ONN is currently limited with its fully-connected recurrent architecture to solve auto-associative memory problems. In this work, we use an alternative two-layer bidirectional ONN architecture. We introduce a two-layer feedforward ONN architecture to perform image edge detection, using the ONN to replace convolutional filters to scan the image. Using an HNN Matlab emulator and digital ONN design simulations, we report efficient image edge detection from both architectures using various size filters (3 × 3, 5 × 5, and 7 × 7) on black and white images. In contrast, the feedforward architectures can also perform image edge detection on gray scale images. With the digital ONN design, we also assess latency performances and obtain that the bidirectional architecture with a 3 × 3 filter size can perform image edge detection in real-time (camera flow from 25 to 30 images per second) on images with up to 128 × 128 pixels while the feedforward architecture with same 3 × 3 filter size can deal with 170 × 170 pixels, due to its faster computation.
Weather drives variation in COVID-19 transmission and detection
Authors: Rising James , Linsenmeier Manuel , De Menezes Ana
Published: January 2023

The debate over the influence of weather on COVID-19 epidemiological dynamics remains unsettled as multiple factors are conflated, including viral biology, transmission through social interaction, and the probability of disease detection. Here we distinguish the distinct dynamics of weather on detection and transmission with a multi-method approach combining econometric techniques with epidemiological models, including an extension of a susceptible-exposed-infectious-recovered model, to analyse data for over 4000 geographic units throughout the year 2020. We find distinct and significant effects of temperature, thermal comfort, solar radiation, and precipitation on the growth of infections. We also find that weather affects the rates of both disease transmission and detection. When we isolate transmission effects to understand the potential for seasonal shifts, the instantaneous effects of weather are small, with R0 about 0.007 higher in winter than in summer. However, the effects of weather compound over time, so that a region with a 5 ∘C drop over three months in winter is expected to have 190% more confirmed cases at the end of that 90 days period, relative to a scenario with constant temperature. We also find that the contribution of weather produces the largest effects in high-latitude countries. As the COVID-19 pandemic continues to evolve and risks becoming endemic, these seasonal dynamics may play a crucial role for health policy.
Quantitative morphometric changes in vascular mild cognitive impairment patients: early diagnosis of dementia
Authors: Guan Jitian , Li Qiuyu , Dai Zhuozhi , Lai Lingfeng , Sun Shuyi , Geng Yiqun , Shen Zhiwei , Luo Lan , Jia Yanlong , Yang Lin , Tang Yanyan , Yan Gen , Wu Renhua
Published: January 2023

Vascular mild cognitive impairment (VMCI) is an early and reversible stage of dementia. Volume differences in regional gray matter may reveal the development and prognosis of VMCI. This study selected 2 of the most common types of VMCI, namely, periventricular white matter hyperintensities (PWMH, n = 14) and strategic single infarctions (SSI, n = 10), and used the voxel-based morphometry method to quantify their morphological characteristics. Meanwhile, age- and sex-matched healthy volunteers were included (n = 16). All the participants were neuropsychologically tested to characterize their cognitive function and underwent whole-brain magnetic resonance imaging scanning. Our results showed that the volumes of the bilateral temporal lobes and bilateral frontal gray matter were obviously diminished in the PWMH group. The atrophy volume difference was 4,086 voxels in the left temporal lobe, 4,154 voxels in the right temporal lobe, 1,718 voxels in the left frontal lobe, and 1,141 voxels in the right frontal lobe (P ≤ 0.001). Moreover, the characteristics of the gray matter atrophy associated with the PWMH were more similar to those associated with Alzheimer’s disease than SSI, which further revealed the susceptibility for escalation from PWMH to dementia. In conclusion, PWMH patients and SSI patients have different morphological characteristics, which explain the different prognoses of VMCI.
Non-invasive detection of cardiac allograft rejection among heart transplant recipients using an electrocardiogram based deep learning model
Authors: Adedinsewo Demilade , Hardway Heather D , Morales-Lara Andrea Carolina , Wieczorek Mikolaj A , Johnson Patrick W , Douglass Erika J , Dangott Bryan J , Nakhleh Raouf E , Narula Tathagat , Patel Parag C , Goswami Rohan M , Lyle Melissa A , Heckman Alexander J , Leoni-Moreno Juan C , Steidley D Eric , Arsanjani Reza , Hardaway Brian , Abbas Mohsin , Behfar Atta , Attia Zachi I , Lopez-Jimenez Francisco , Noseworthy Peter A , Friedman Paul , Carter Rickey E , Yamani Mohamad
Published: January 2023

Aims

Current non-invasive screening methods for cardiac allograft rejection have shown limited discrimination and are yet to be broadly integrated into heart transplant care. Given electrocardiogram (ECG) changes have been reported with severe cardiac allograft rejection, this study aimed to develop a deep-learning model, a form of artificial intelligence, to detect allograft rejection using the 12-lead ECG (AI-ECG).

Methods and results

Heart transplant recipients were identified across three Mayo Clinic sites between 1998 and 2021. Twelve-lead digital ECG data and endomyocardial biopsy results were extracted from medical records. Allograft rejection was defined as moderate or severe acute cellular rejection (ACR) based on International Society for Heart and Lung Transplantation guidelines. The extracted data (7590 unique ECG-biopsy pairs, belonging to 1427 patients) was partitioned into training (80%), validation (10%), and test sets (10%) such that each patient was included in only one partition. Model performance metrics were based on the test set (n = 140 patients; 758 ECG-biopsy pairs). The AI-ECG detected ACR with an area under the receiver operating curve (AUC) of 0.84 [95% confidence interval (CI): 0.78–0.90] and 95% (19/20; 95% CI: 75–100%) sensitivity. A prospective proof-of-concept screening study (n = 56; 97 ECG-biopsy pairs) showed the AI-ECG detected ACR with AUC = 0.78 (95% CI: 0.61–0.96) and 100% (2/2; 95% CI: 16–100%) sensitivity.

Conclusion

An AI-ECG model is effective for detection of moderate-to-severe ACR in heart transplant recipients. Our findings could improve transplant care by providing a rapid, non-invasive, and potentially remote screening option for cardiac allograft function.
Contrasting Genomic Evolution Between Domesticated and WildKluyveromyces lactisYeast Populations
Authors: Friedrich Anne , Gounot Jean-Sébastien , Tsouris Andreas , Bleykasten Claudine , Freel Kelle , Caradec Claudia , Schacherer Joseph
Published: January 2023

The process of domestication has variable consequences on genome evolution leading to different phenotypic signatures. Access to the complete genome sequences of a large number of individuals makes it possible to explore the different facets of this domestication process. Here, we sought to explore the genome evolution of Kluyveromyces lactis, a yeast species well known for its involvement in dairy processes and also present in natural environments. Using a combination of short- and long-read sequencing strategies, we investigated the genomic variability of 41 K. lactis isolates and found that the overall genetic diversity of this species is very high (θw = 3.3 × 10−2) compared with other species such as Saccharomyces cerevisiae (θw = 1.6 × 10−2). However, the domesticated dairy population shows a reduced level of diversity (θw = 1 × 10−3), probably due to a domestication bottleneck. In addition, this entire population is characterized by the introgression of the LAC4 and LAC12 genes, responsible for lactose fermentation and coming from the closely related species, Kluyveromyces marxianus, as previously described. Our results highlighted that the LAC4/LAC12 gene cluster was acquired through multiple and independent introgression events. Finally, we also identified several genes that could play a role in adaptation to dairy environments through copy number variation. These genes are involved in sugar consumption, flocculation, and drug resistance, and may play a role in dairy processes. Overall, our study illustrates contrasting genomic evolution and sheds new light on the impact of domestication processes on it.
Industry concentration in Europe and North America
Authors: Bajgar Matej , Berlingieri Giuseppe , Calligaris Sara , Criscuolo Chiara , Timmis Jonathan
Published: January 2023

This paper presents new evidence on industry concentration at both the country and the world-region levels. It calculates country-level industry concentration measures from the novel data representative of the entire firm population in 12 European countries, and it develops a methodology for calculating industry concentration at the supranational level using detailed cross-country data on subsidiaries of business groups. This paper documents that industry concentration has increased not only in North America but also in Europe since 2000, albeit to a lesser extent.
Peripheral blood persistence and expansion of transferred non-genetically modified Natural Killer cells might not be necessary for clinical activity
Authors: Silla Lucia
Published: January 2023

Natural killer (NK) cells are innate lymphocytes that react without previous exposition to virus infected or malignant cells and stimulate adaptive immune response to build a long-lasting immunity against it. To that end, tissue resident NK cells are predominantly regulatory as opposed to cytotoxic. In the hematopoietic stem cell transplant (HSCT) setting, which curative potential relies on the graft versus leukemia effect, NK cells are known to play a significant role. This knowledge has paved the way to the active investigation on its anti-tumor effect outside the stem cell transplant scenario. Based on the relevant literature on the adoptive transfer of non-genetically modified NK cells for the treatment of relapsed/refractory acute leukemia and on our own experience, we discuss the role of donor cell peripheral blood persistence and expansion and its lack of correlation with anti-leukemia activity.
IL-22 Promotes Neural Stem Cell Self-Renewal in the Adult Brain
Authors: Coronas Valérie , Arnault Patricia , Jégou Jean-François , Cousin Laetitia , Rabeony Hanitriniaina , Clarhaut Sandrine , Harnois Thomas , Lecron Jean-Claude , Morel Franck
Published: January 2023

Mainly known for its role in immune defense and inflammation, interleukin 22 (IL-22) has emerged over the past decade as a cytokine involved in the adaptation of stem/progenitor cell activity for tissue homeostasis and repair. IL-22 is present in the brain, which harbors neural stem cells (NSC) in specific niches of which the ventricular-subventricular zone (V-SVZ) is the most important. In this study, we examined a possible effect of IL-22 on NSC in the adult mouse brain. We demonstrate that the IL-22 receptor is expressed in the V-SVZ, mainly in NSC characterized by their SOX2 expression. Addition of IL-22 to V-VSZ cell cultures resulted in an increase in NSC self-renewal, associated with a shift in NSC division mode towards symmetric proliferative divisions at the expense of differentiative divisions. Conversely, loss of IL-22 in knockout mice led to a decrease in neurosphere yield, suggesting a reduction in the NSC population, which was confirmed by the decrease in cells retaining BrdU labeling in IL-22 knockout mice. Our study supports that IL-22 is involved in the development and/or maintenance of V-VSZ NSC and opens new avenues to further investigate the role of IL-22 in NSC biology in health and disease.
Comparative analysis of glass and Hemotek membrane feeding systems for malaria transmission research
Authors: Graumans Wouter , Schinkel Michelle , van Gemert Geert-Jan , Spitzen Jeroen , Bousema Teun , Miesen Pascal
Published: January 2023

Background

Glass membrane feeders are used in malaria research for artificial blood feeding. This study investigates the use of Hemotek membrane feeders as a standardized alternative feeding system.

Methods

Hemotek feeders were compared with glass feeders by assessing mosquito feeding rate, imbibed blood meal volume and Plasmodium falciparum infection intensity on mosquito guts.

Results

While mosquito feeding rate and blood meal volume were comparable between Hemotek and glass feeders, a loss in transmission was observed using the Hemotek feeder with a conventional collagen membrane. There was no difference in transmission between both feeders when Parafilm was used as the membrane.

Conclusions

Hemotek feeders with a Parafilm membrane can be used as an alternative feeding system for malaria transmission research.
Omega-3 fatty acids and cognitive function
Authors: Welty Francine K.
Published: January 2023

Purpose of review

The aim is to provide an update on omega-3 polyunsaturated fatty acids (n-3 PUFA) in preventing cognitive decline and dementia.

Recent findings

Prospective studies and three new meta-analyses suggest that fish or n-3 PUFA intake are associated with a reduction in development of mild cognitive decline and Alzheimer's disease. Supplementation with docosahexaenoic acid (DHA) in randomized controlled trials (RCTs) in those with mild cognitive impairment showed benefit on cognitive decline, whereas there was no benefit in Alzheimer's disease. In cognitively healthy individuals with clinical coronary artery disease (CAD), 3.36 g EPA and DHA daily slowed cognitive ageing by 2.5 years. Of 15 RCTs in cognitively healthy individuals age more than 55 years, seven reported benefit, whereas eight did not. Potential mechanisms for differences in outcomes include dose, trial duration, apolipoproteinE genotype, sex, stage and rate of cognitive decline, cognitive testing employed and individual characteristics. The downstream product of DHA, neuroprotectin D1, may be involved in beneficial effects.

Patients with early memory complaints or a family history of dementia and those with CAD should be counselled on the potential benefits of fish intake and supplementation with n-3 PUFA. ApolipoproteinE4 carriers may especially benefit from DHA supplementation prior to development of cognitive decline.
Orthopaedic trauma observerships in North America for international surgeons: the visitors' perspective
Authors: Urva Mayur , Cortez Abigail , Katyal Toshali , Shearer David W. , Morshed Saam , Miclau Theodore , MacKechnie Madeline C. , Sabharwal Sanjeev ,   COACT Study Group
Published: January 2023

Objective:

International observerships are one of many efforts aimed at addressing disparities in orthopaedic trauma care globally. However, their impact on visiting surgeons and their home countries, as well as the challenges faced by participating surgeons, are not well-documented.

Methods:

A survey was distributed to overseas surgeons who participated in an orthopaedic trauma observership from 2009 to 2020. Surgeons were identified through North American institutions previously recognized by the authors as having hosted international observerships. Information gathered included participant demographics, details of and perceived impact of the observership, and barriers faced before, during, and after the program. Responses from 148 international surgeons (ISs) from 49 countries were analyzed.

Results:

Sixty percent of observerships were at academic programs, 57% lasted 1–3 months, and 60% were self-funded. Participants identified cost and housing as primary barriers. After completing their observership, lack of funding, equipment and support staff, and excessive workload prevented participants from implementing changes at their clinical practice. Most observers believed that they gained relevant clinical (89%) and surgical knowledge (67%) and developed a professional network of North American hosts (63%). The most common suggested changes to the observership were greater hands-on experience in the operating room and structured goal setting relevant to the visiting surgeon.

Conclusions:

Visiting surgeons find North American orthopaedic trauma observerships helpful in improving their surgical and clinical skills. However, financial constraints and resource limitations at their clinical practice and limited operative experience during the observership present barriers to maximizing this clinical experience. To enhance the relevance of clinical observerships for ISs and impact global orthopaedic trauma care, the unique needs and challenges facing ISs must be addressed.

Level of Evidence:

IV—Cross-Sectional Study.
Multi-omic identification of key transcriptional regulatory programs during endurance exercise training
Authors: Smith Gregory R. , Zhao Bingqing , Lindholm Malene E. , Raja Archana , Viggars Mark , Pincas Hanna , Gay Nicole R. , Sun Yifei , Ge Yongchao , Nair Venugopalan D. , Sanford James A. , Amper Mary Anne S. , Vasoya Mital , Smith Kevin S. , Montgomer Stephen , Zaslavsky Elena , Bodine Sue C. , Esser Karyn A. , Walsh Martin J. , Snyder Michael P. , Sealfon Stuart C. ,   the MoTrPAC Study Group
Published: January 2023

Transcription factors (TFs) play a key role in regulating gene expression and responses to stimuli. We conducted an integrated analysis of chromatin accessibility, DNA methylation, and RNA expression across eight rat tissues following endurance exercise training (EET) to map epigenomic changes to transcriptional changes and determine key TFs involved. We uncovered tissue-specific changes and TF motif enrichment across all omic layers, differentially accessible regions (DARs), differentially methylated regions (DMRs), and differentially expressed genes (DEGs). We discovered distinct routes of EET-induced regulation through either epigenomic alterations providing better access for TFs to affect target genes, or via changes in TF expression or activity enabling target gene response. We identified TF motifs enriched among correlated epigenomic and transcriptomic alterations, DEGs correlated with exercise-related phenotypic changes, and EET-induced activity changes of TFs enriched for DEGs among their gene targets. This analysis elucidates the unique transcriptional regulatory mechanisms mediating diverse organ effects of EET.
Multimodal HLA-I genotype regulation by human cytomegalovirus US10 and resulting surface patterning
Authors: Gerke Carolin , Bauersfeld Liane , Oberhardt Valerie , Jürges Christopher Sebastian , Spaapen Robbert M. , Mussolino Claudio , Le-Trilling Vu Thuy Khanh , Trilling Mirko , Dölken Lars , Erhard Florian , Hofmann Maike , Hengel Hartmut , Momburg Frank , Halenius Anne
Published: January 2023

To control human cytomegalovirus (HCMV) infection, NK cells and CD8+T-cells are crucial. HLA class I (HLA-I) molecules play a central role for both NK and T-cell responses and are targets of multifaceted HCMV-encoded immunoevasins. A so far insufficiently studied HLA-I immunoevasin is the glycoprotein US10. It was shown that US10 targets HLA-G, but it is unknown whether US10 contributes also to escape from classical HLA-I antigen presentation. Our biochemical analysis revealed that early during maturation, all investigated HLA-I (HLA-A/B/C/E/G) heavy chains are recognized and bound by US10. Remarkably, the consequences of this initial binding strongly depended on both the HLA-I geno- and allotypes: i) HLA-A molecules escaped down-regulation by US10, ii) tapasin-dependent HLA-B molecules exhibited impaired recruitment to the peptide loading complex and maturation, iii) HLA-C and HLA-G, but not HLA-A/B/E, strongly bound US10 also in their β2m-assembled form. Thus, US10 senses geno- and allotypic differences in a so far unparalleled and multimodal manner, suggestive of adaptation to HLA-I genotype differences. At a further level of complexity, in HCMV-infected fibroblasts inhibition of overlappingUS10andUS11transcription revealed an additional HLA-I specificity, suggesting targeting of HLA-I in a synergistically arranged manner. Our study unveils the exceptional HLA-I selectivity of HCMV-encoded US10 and underlines its contribution to immune escape.
Improving the predictive performance of CLUE-S by extending demand to land transitions: the trans-CLUE-S model
Authors: Kiziridis Diogenis A. , Mastrogianni Anna , Pleniou Magdalini , Tsiftsis Spyros , Xystrakis Fotios , Tsiripidis Ioannis
Published: January 2023

The CLUE-S model is a popular choice for modelling land use and land cover change from local to regional scales, but it spatially allocates the demand for only the total cover of each land class in the predicted map. In the present work, we introduce a CLUE-S variant that allocates demand at the more detailed level of land type transitions, the trans-CLUE-S model. We implemented this extension algorithmically in R, without the need of new parameters. By processing each row of the land transition matrix separately, the model allocates the demand of each land category’s transitions via the CLUE-S allocation routine for only the cells which were of that category in the map of the previous time step. We found that the trans-CLUE-S model had half the total and configuration disagreement of the CLUE-S predictions in an empirical landscape, and in simulated landscapes of different characteristics. Moreover, the trans-CLUE-S performance was less sensitive to the number of environmental predictors of land type suitability for allocating demand. Although trans-CLUE-S is computationally more demanding due to running a CLUE-S allocation for each land class, we appended the solution of a land-use assignment optimisation problem that facilitates the convergence and acceleration of allocation. We additionally provide R functions for: CLUE-S variants at other levels of demand resolution; random instead of environment-based allocation; and for simulating landscapes of desired characteristics. Our R code for the models and functions can contribute to more reproducible, transparent and accurate modelling, analysis and interpretation of land cover change.

Highlights

The trans-CLUE-S model employs demand at the finer level of land type transitions

The trans-CLUE-S predictions were twice more accurate than the CLUE-S model’s

The trans-CLUE-S accuracy was less dependent on the amount of environmental data

Algorithmic addition of a land assignment task enabled and sped up full convergence

R code is provided for our models and auxiliary functions
Design of 8-mer Peptides that BlockClostridioides difficileToxin A in Intestinal Cells
Authors: Sarma Sudeep , Catella Carly M. , Pedro Ellyce T. San , Xiao Xingqing , Durmusoglu Deniz , Menegatti Stefano , Crook Nathan , Magness Scott T. , Hall Carol K.
Published: January 2023

Clostridioides difficile(C. diff.) is a bacterium that causes severe diarrhea and inflammation of the colon. The pathogenicity ofC. diff. infection is derived from two major toxins, toxins A (TcdA) and B (TcdB). Peptide inhibitors that can be delivered to the gut to inactivate these toxins are an attractive therapeutic strategy. In this work, we present a new approach that combines apeptidebindingdesign algorithm (PepBD), molecular-level simulations, rapid screening of candidate peptides for toxin binding, a primary human cell-based assay, and surface plasmon resonance (SPR) measurements to develop peptide inhibitors that block the glucosyltransferase activity of TcdA by targeting its glucosyltransferase domain (GTD). Using PepBD and explicit-solvent molecular dynamics simulations, we identified seven candidate peptides, SA1-SA7. These peptides were selected for specific TcdA GTD binding through a custom solid-phase peptide screening system, which eliminated the weaker inhibitors SA5-SA7. The efficacies of SA1-SA4 were then tested using a trans-epithelial electrical resistance (TEER) assay on monolayers of the human gut epithelial culture model. One peptide, SA1, was found to block TcdA toxicity in primary-derived human jejunum (small intestinal) and colon (large intestinal) epithelial cells. SA1 bound TcdA with a KDof 56.1 ± 29.8 nM as measured by surface plasmon resonance (SPR).

Significance Statement

Infections byClostridioides difficile, a bacterium that targets the large intestine (colon), impact a significant number of people worldwide. Bacterial colonization is mediated by two exotoxins: toxins A and B. Short peptides that can inhibit the biocatalytic activity of these toxins represent a promising strategy to prevent and treatC. diff. infection. We describe an approach that combines aPeptide BindingDesign (PepBD) algorithm, molecular-level simulations, a rapid screening assay to evaluate peptide:toxin binding, a primary human cell-based assay, and surface plasmon resonance (SPR) measurements to develop peptide inhibitors that block Toxin A in small intestinal and colon epithelial cells. Importantly, our designed peptide, SA1, bound toxin A with nanomolar affinity and blocked toxicity in colon cells.
Determining Best Practice for the Spatial Poisson Process in Species Distribution Modelling
Authors: Bellew Sean , Flint Ian , Wang Yan
Published: January 2023

Poisson processes have become a prominent tool in species distribution modelling when analysing citizen science data based on presence records. This study examines four distinct statistical approaches, each of which utilises a different approximation to fit a Poisson point process. These include two Poisson regressions with either uniform weights or the more elaborate Berman-Turner device, as well as two logistic regressions, namely the infinitely weighted logistic regression method and Baddeley’s logistic regression developed in the context of spatial Gibbs processes. This last method has not been considered in depth in the context of Poisson point processes in the previous literature. A comprehensive comparison has been conducted on the performance of these four approaches using both simulated and actual presence data sets. When the number of dummy points is sufficiently large, all approaches converge, with the Berman-Turner device demonstrating the most consistent performance. A Poisson process model was developed to accurately predict the distribution of Arctotheca calendula, an invasive weed in Australia that does not appear to have been the subject of any species niche modelling analysis in the existing literature. Our findings are valuable for ecologists and other non-statistical experts who wish to implement the best practices for predicting species’ distribution using Poisson point processes.
Cooperative hydrodynamics accompany multicellular-like colonial organization in the unicellular ciliateStentor
Authors: Shekhar Shashank , Guo Hanliang , Colin Sean P. , Marshall Wallace , Kanso Eva , Costello John H.
Published: January 2023

Evolution of multicellularity from early unicellular ancestors is arguably one of the most important transitions since the origin of life1,2. Multicellularity is often associated with higher nutrient uptake3, better defense against predation, cell specialization and better division of labor4. While many single-celled organisms exhibit both solitary and colonial existence3,5,6, the organizing principles governing the transition and the benefits endowed are less clear. Using the suspension-feeding unicellular protistStentor coeruleus, we show that hydrodynamic coupling between proximal neighbors results in faster feeding flows that depend on the separation between individuals. Moreover, we find that the accrued benefits in feeding current enhancement are typically asymmetric– individuals with slower solitary currents gain more from partnering than those with faster currents. We find that colony-formation is ephemeral inStentorand individuals in colonies are highly dynamic unlike other colony-forming organisms likeVolvox carteri3. Our results demonstrate benefits endowed by the colonial organization in a simple unicellular organism and can potentially provide fundamental insights into the selective forces favoring early evolution of multicellular organization.
Perilaryngeal Functional Muscle Network in Patients with Vocal Hyperfunction - A Case Study
Authors: O’Keeffe Rory , Shirazi Seyed Yahya , Mehrdad Sarmad , Crosby Tyler , Johnson Aaron M. , Atashzar S. Farokh
Published: January 2023

Patients with both phonotraumatic and non-phonotraumatic dysphonia commonly present with vocal hyperfunction, defined as excessive perilaryngeal muscle activity and characterized by muscular pain and strain in the neck, increased vocal effort, and vocal fatigue. The inability to reliably measure vocal hyperfunction is a barrier to adequate evaluation and treatment of hyperfunctional voice disorders. We have recently demonstrated that the perilaryngeal functional muscle network can be a novel sensitive neurophysiological window to vocal performance in vocally healthy subjects. In this paper, for the first time, we evaluate the performance and symmetry of functional perilaryngeal muscle networks in three patients with voice disorders. Surface electromyography signals were recorded from twelve sensors (six on each side of the neck) using the wireless Trigno sEMG system (Delsys Inc., Natick, MA). Patient 1 was diagnosed with primary muscle tension dysphonia, Patient 2 was diagnosed with unilateral vocal fold paresis, and Patient 3 was diagnosed with age-related glottal insufficiency. This paper reports altered functional connectivity and asymmetric muscle network scan behavior in all three patients when compared with a cohort of eight healthy subjects. Our approach quantifies synergistic network activity to interrogate coordination of perilaryngeal and surrounding muscles during voicing and potentialdiscoordinationof the muscle network for dysphonic conditions. Asymmetry in muscle networks is proposed here as a biomarker for monitoring vocal hyperfunction.
OpaR exerts a dynamic control over c-di-GMP homeostasis andcpsAexpression inV. parahaemolyticusthrough its regulation of ScrC and the trigger phosphodiesterase TpdA
Authors: Zamorano-Sánchez David , Alejandre-Sixtos Jesús E. , Arredondo-Hernández Adilene , Martínez-Méndez Raquel
Published: January 2023

The second messenger cyclic dimeric guanosine monophosphate (c-di-GMP) plays a central role in controlling decision making processes of vital importance for the environmental survival of the human pathogenVibrio parahaemolyticus. The mechanisms by which c-di-GMP levels are dynamically controlled inV. parahaemolyticusare poorly understood. Here we report our findings regarding the involvement of OpaR in controlling c-di-GMP metabolism in planktonic and surface-attached cells through controlling the expression of the trigger phosphodiesterase (PDE) TpdA and other PDEs such as ScrC. Our results revealed that OpaR negatively modulates the expression oftpdAby maintaining a baseline level of c-di-GMP. The OpaR-regulated PDEs ScrC, ScrG and VP0117 enable the upregulation oftpdA, to a different degree, in the absence of OpaR. We also found that TpdA plays the dominant role in c-di-GMP degradation under planktonic conditions compared to the other OpaR-regulated PDEs. In cells growing over solid media the dominant c-di-GMP degrader role is played by ScrC for 72 hours and passes to TpdA after 96 hours of growth. We also report negative and positive effects of the absence of OpaR oncpsAexpression in cells growing over solid media or forming biofilms over glass, respectively. These results suggest that OpaR can act as a double-edged sword to control c-di-GMP accumulation andcpsAexpression positively or negatively in response to poorly understood environmental factors. Finally, through anin-silicoanalysis we point out outlets of the OpaR regulatory module that can impact decision making during the motile to sessile transition inV. parahaemolyticus.

Importance

The second messenger c-di-GMP is extensively used by bacterial cells to control crucial social adaptations such as biofilm formation. Here we explore the role of the quorum-sensing regulatorOpaR, from the human pathogenV. parahaemolyticus, on the dynamic control of c-di-GMP signaling. We found that OpaR can regulate positively or negatively c-di-GMP accumulation depending on the growth conditions. This dual role has not been reported for orthologues of OpaR, such as HapR fromV. cholerae. OpaR controls c-di-GMP homeostasis through PDEs that are absent inV. cholerae, pointing toward further differences in c-di-GMP signaling in these two pathogens. It is important to investigate the origins and consequences of these differences to better understand pathogenic bacterial behavior and its evolution.
Genomic characterization of multidrug-resistant extended spectrum β-lactamase-producingKlebsiella pneumoniaefrom clinical samples of a tertiary hospital in South Kivu Province, eastern Democratic Republic of Congo
Authors: Irenge Leonid M. , Ambroise Jérôme , Bearzatto Bertrand , Durant Jean-François , Bonjean Maxime , Gala Jean-Luc
Published: January 2023

Multidrug-resistant (MDR) and Extended Spectrum β-Lactamase (ESBL)-producing extraintestinalK. pneumoniaeare associated with increased morbidity and mortality. This study aimed to characterize the resistance and virulence profiles of extra-intestinal MDR ESBL-producingK. pneumoniaeassociated with infections at a tertiary hospital in South-Kivu province, DRC. Whole-genome sequencing (WGS) was carried out on 37 K.pneumoniaeisolates displaying MDR, and ESBL-producing phenotype. The assembled genomes were analysed for phylogeny, virulence factors and antimicrobial resistance genes determinants. These isolates were compared to sub-Saharan counterparts.K. pneumoniaeisolates displayed a high genetic variability with up to 16 sequence types (ST). AMR was widespread against β-lactamases (including third and fourth-generation cephalosporins, but not carbapenems), aminoglycosides, ciprofloxacin, tetracycline, erythromycin, nitrofurantoin, and cotrimoxazole. TheblaCTXM-15gene was the most common β-lactamase gene amongK. pneumoniaeisolates. No carbapenemase gene was found. ARG for aminoglycosides, quinolones, phenicols, tetracyclines, sulfonamides, nitrofurantoin were widely distributed among the isolates. Nine isolates had the colistin-resistant R256G substitution in thepmrBefflux pump gene without displaying reduced susceptibility to colistin. Despite carrying virulence genes, none had hypervirulence genes. Our results highlight the genetic diversity of MDR ESBL-producingK. pneumoniaeisolates, and underscore the importance of monitoring simultaneously the evolution of phenotypic and genotypic AMR in Bukavu and DRC, while calling for caution in administering colistin and carbapenem to patients.
A precision overview of genomic resistance screening in isolates ofMycobacterium tuberculosisusing web-based bioinformatics tools
Authors: Morey-León Gabriel , Mejía-Ponce Paulina M. , Granda Pardo Juan Carlos , Muñoz-Mawyin Karen , Fernández-Cadena Juan Carlos , García-Moreira Evelyn , Andrade-Molina Derly , Licona-Cassani Cuauhtémoc , Berná Luisa
Published: January 2023

Tuberculosis (TB) is among the most deadly diseases that affect worldwide, its impact is mainly due to the continuous emergence of resistant isolates during treatment due to the laborious process of resistance diagnosis, non-adherence to treatment and circulation of previously resistant isolates ofMycobacterium tuberculosis. The aim in this study was evaluate the performance and functionalities of web-based tools: Mykrobe, TB-profiler, PhyReSse, KvarQ, and SAM-TB for detecting resistance in isolate ofMycobacterium tuberculosisin comparison with conventional drug susceptibility tests. We used 88M. tuberculosisisolates which were drug susceptibility tested and subsequently fully sequenced and web-based tools analysed. Statistical analysis was performed to determine the correlation between genomic and phenotypic analysis. Our data show that the main sub-lineage was LAM (44.3%) followed by X-type (23.0%) within isolates evaluated. Mykrobe has a higher correlation with DST (98% of agreement and 0.941Cohen’s Kappa) for global resistance detection, but SAM-TB, PhyReSse and Mykrobe had a better correlation with DST for first-line drug analysis individually. We have identified that 50% of mutations characterised by all web-based tools were canonical inrpoB, katG, embB, pncA, gyrAandrrsregions. Our findings suggest that SAM-TB, PhyReSse and Mykrobe were the web-based tools more efficient to determine canonical resistance-related mutations, however more analysis should be performed to improve second-line detection. The improvement of surveillance programs for the TB isolates applying WGS tools against first line drugs, MDR-TB and XDR-TB are priorities to discern the molecular epidemiology of this disease in the country.

Importance

Tuberculosis, an infectious disease caused byMycobacterium tuberculosis, which most commonly affects the lungs and is often spread through the air when infected people cough, sneeze, or spit. However, despite the existence of effective drug treatment, the patient adherence, long duration of treatment, and late diagnosis, have reduced the effectiveness of therapy and raised the drug resistance. The increase in resistant cases, added to the impact of the COVID-19 pandemic, have highlighted the importance of implementing efficient and timely diagnostic methodologies worldwide. The significance of our research is in evaluating and identifying the more efficient and friendly web-based tool to characterise the resistance inMycobacterium tuberculosisby whole genome sequencing, which will allow apply it more routinely to improve TB strain surveillance programs locally.
“You have to add your own character”: Medical Student Perspectives on Observing Clinical Encounters
Authors: Poeppelman Rachel Stork , Fromme H Barrett , Yudkowsky Rachel , Lineberry Matthew , Hirshfield Laura
Published: January 2023

Introduction

The authors aimed to investigate how medical students interpret the observation of a more experienced clinician modeling both exemplaryandflawed behaviors as well as how that interpretation influences their subsequent clinical performance.

Methods

We presented a recorded patient sexual history to 11 medical students. The recording displayed both exemplary and flawed behaviors. Students then obtained a sexual history from a standardized patient themselves. Using an interview methodology and constructivist analytic approach, we explored the process of learning from clinical observations.

Results

Students attended to flawed modeled behaviors, challenges specific to the task, and how areas of their own personal development were accomplished. They took a piecemeal approach to classifying modeled behaviors as done well or poorly based on previous instruction, experience, or perceived downstream effects. When applying their observations, students choose to copy, adapt, or avoid modeled behaviors based on their classification of the behavior.

Discussion

To optimize learning from observation, faculty can identify task-specific challenges and a student’s personal goals, which naturally draw the student’s attention, before observation in order to develop a shared mental model. When debriefing observed encounters, faculty may consider natural targets of learner attention, challenges specific to learning from observation, and factors likely to influence a learner’s judgement of modeled behaviors.
Measuring prion propagation in single bacteria elucidates mechanism of loss
Authors: Jager Krista , Orozco-Hidalgo Maria Teresa , Springstein Benjamin Lennart , Joly-Smith Euan , Papazotos Fotini , McDonough EmilyKate , Fleming Eleanor , McCallum Giselle , Hilfinger Andreas , Hochschild Ann , Potvin-Trottier Laurent
Published: January 2023

Prions are self-propagating protein aggregates formed by specific proteins that can adopt alternative folds. Prions were discovered as the cause of the fatal transmissible spongiform encephalopathies in mammals, but prions can also constitute non-toxic protein-based elements of inheritance in fungi and other species. Prion propagation has recently been shown to occur in bacteria for more than a hundred cell divisions, yet a fraction of cells in these lineages lost the prion through an unknown mechanism. Here, we investigate prion propagation in single bacterial cells as they divide using microfluidics and fluorescence microscopy. We show that the propagation occurs in two distinct modes with distinct stability and inheritance characteristics. We find that the prion is lost through random partitioning of aggregates to one of the two daughter cells at division. Extending our findings to prion domains from two orthologous proteins, we observe similar propagation and loss properties. Our findings also provide support for the suggestion that bacterial prions can form more than one self-propagating state. We implement a stochastic version of the molecular model of prion propagation from yeast and mammals that recapitulates all the observed single-cell properties. This model highlights challenges for prion propagation that are unique to prokaryotes and illustrates the conservation of fundamental characteristics of prion propagation across domains of life.
Deep learning prediction boosts phosphoproteomics-based discoveries through improved phosphopeptide identification
Authors: Yi Xinpei , Wen Bo , Ji Shuyi , Saltzman Alex , Jaehnig Eric J. , Lei Jonathan T. , Gao Qiang , Zhang Bing
Published: January 2023

Shotgun phosphoproteomics enables high-throughput analysis of phosphopeptides in biological samples, but low phosphopeptide identification rate in data analysis limits the potential of this technology. Here we present DeepRescore2, a computational workflow that leverages deep learning-based retention time and fragment ion intensity predictions to improve phosphopeptide identification and phosphosite localization. Using a state-of-the-art computational workflow as a benchmark, DeepRescore2 increases the number of correctly identified peptide-spectrum matches by 17% in a synthetic dataset and identifies 19%-46% more phosphopeptides in biological datasets. In a liver cancer dataset, 30% of the significantly altered phosphosites between tumor and normal tissues and 60% of the prognosis-associated phosphosites identified from DeepRescore2-processed data could not be identified based on the state-of-the-art workflow. Notably, DeepRescore2-processed data uniquely identifies EGFR hyperactivation as a new target in poor-prognosis liver cancer, which is validated experimentally. Integration of deep learning prediction in DeepRescore2 improves phosphopeptide identification and facilitates biological discoveries.
Major axes of variation in tree demography across global forests
Authors: Leite Melina de Souza , McMahon Sean M. , Prado Paulo Inácio , Davies Stuart J. , Oliveira Alexandre Adalardo de , De Deurwaerder Hannes P. , Aguilar Salomón , Anderson-Teixeira Kristina J. , Aqilah Nurfarah , Bourg Norman A. , Brockelman Warren Y. , Castaño Nicolas , Chang-Yang Chia-Hao , Chen Yu-Yun , Chuyong George , Clay Keith , Duque Álvaro , Ediriweera Sisira , Ewango Corneille E.N. , Gilbert Gregory , Gunatilleke I.A.U.N. , Gunatilleke C.V.S. , Howe Robert , Huasco Walter Huaraca , Itoh Akira , Johnson Daniel J. , Kenfack David , Král Kamil , Leong Yao Tze , Lutz James A. , Makana Jean-Remy , Malhi Yadvinder , McShea William J. , Mohamad Mohizah , Nasardin Musalmah , Nathalang Anuttara , Parker Geoffrey , Parmigiani Renan , Pérez Rolando , Phillips Richard P. , Šamonil Pavel , Sun I-Fang , Tan Sylvester , Thomas Duncan , Thompson Jill , Uriarte María , Wolf Amy , Zimmerman Jess , Zuleta Daniel , Visser Marco D. , Hülsmann Lisa
Published: January 2023

The future trajectory of global forests is closely intertwined with tree demography, and a major fundamental goal in ecology is to understand the key mechanisms governing spatial-temporal patterns in tree population dynamics. While historical research has made substantial progress in identifying the mechanisms individually, their relative importance among forests remains unclear mainly due to practical limitations. One approach is to group mechanisms according to their shared effects on the variability of tree vital rates and to quantify patterns therein. We developed a conceptual and statistical framework (variance partitioning of Bayesian multilevel models) that attributes the variability in tree growth, mortality, and recruitment to variation in species, space, and time, and their interactions, categories we refer to asorganising principles(OPs). We applied the framework to data from 21 forest plots covering more than 2.9 million trees of approximately 6,500 species. We found that differences among species, thespeciesOP, proved a major source of variability in tree vital rates, explaining 28-33% of demographic variance alone, and in interaction withspace14-17%, totalling 40-43%. The average variability among species declined with species richness across forests, indicating that diverse forests featured smaller interspecific differences in vital rates supporting the theory that the range of vital rates is similar across global forests. Decomposing the variance in vital rates into the proposed OPs showed that taxonomy is crucial to predicting and understanding tree demography on large forest plots. A focus on how variance is organized in forests can facilitate the construction of more targeted models with clearer expectations of which covariates might drive a vital rate. This study therefore highlights the most promising avenues for future research, both in terms of understanding the relative contributions of groups of mechanisms to forest demography and diversity, and for improving projections of forest ecosystems.
Helical Intermediate Formation and Its Role in Amyloid of an Amphibian Antimicrobial Peptide†
Authors: Prasad Anup Kumar , Martin Lisandra L. , Panwar Ajay S.
Published: January 2023

Helical intermediates appear to be crucial in amyloid formation of several amyloidogenic peptides, including Aβ, that are implicated in different neurodegenerative diseases. Intermediate species have been reported to be more toxic than mature amyloid fibrils. Hence, the focus of the current work is to understand both structural and mechanistic role of intermediates in the early stages of amyloid self-assembly in amyloidogenic peptides. Molecular dynamics (MD) simulations and the adaptive biasing force (ABF) method were utilized to investigate structural changes that lead to amyloid formation in amphibian peptide uperin-3.5 (U3.5), an antimicrobial and amyloidogenic peptide. Microsecond time-scale MD simulations revealed that peptide aggregation, intoβ-sheet dominated aggregates, is centred on two important factors; evolution ofα-helical intermediates and the critical role of local peptide concentration inside these aggregates. Electrostatic attraction between the oppositely charged aspartate (D) and arginine (R) residues located near the N-terminus induced hydrogen bonding resulting in formation of precursor 310-helices close to the N-terminus. The 310-helices transitioned intoα-helices, thereby imparting partial helical conformations to the peptides. In the initial stages of aggregation, U3.5 peptides with amphipathic, partial helices aggregated to form small clusters of helical intermediates directed via hydrophobic interactions. These helices imparted stability to the helical intermediates, which promoted growth of clusters by further addition of peptides. This led to an increase in the local peptide concentration which enabled stronger peptide-peptide interactions and triggered aβ-sheet transition in these aggregates. Thus, the study emphasized that stabilisation of peptide helical content may be crucial to the evolution ofβ-sheet-rich amyloid structures.