bluuebunny/crossref_metadata_2025 huggingface dataset:
Association Between Levels of Intensive Care and In-Hospital Mortality in Patients Hospitalized for Sepsis Stratified by Sequential Organ Failure Assessment Scores*
Authors: Ohbe Hiroyuki , Sasabuchi Yusuke , Doi Kent , Matsui Hiroki , Yasunaga Hideo
Published: April 2023

OBJECTIVES:

To assess the association between levels of intensive care and in-hospital mortality in patients hospitalized for sepsis, stratified by Sequential Organ Failure Assessment (SOFA) score at admission.

DESIGN:

A nationwide, propensity score-matched, retrospective cohort study.

SETTING:

A Japanese national inpatient database with data on 70–75% of all ICU and high-dependency care unit (HDU) beds in Japan.

PATIENTS:

Adult patients hospitalized for sepsis with SOFA scores greater than or equal to 2 on their day of admission between April 1, 2018, and March 31, 2021, were recruited. Propensity score matching was performed to compare in-hospital mortality, and patients were stratified into 10 groups according to SOFA scores.

INTERVENTIONS:

Two exposure and control groups according to treatment unit on day of admission: 1) ICU + HDU versus general ward and 2) ICU versus HDU.

MEASUREMENTS AND MAIN RESULTS:

Of 97,070 patients, 19,770 (20.4%), 23,066 (23.8%), and 54,234 (55.9%) were treated in ICU, HDU, and general ward, respectively. After propensity score matching, the ICU + HDU group had significantly lower in-hospital mortality than the general ward group, among cohorts with SOFA scores greater than or equal to 6. There were no significant differences in in-hospital mortality among cohorts with SOFA scores 3–5. The ICU + HDU group had significantly higher in-hospital mortality than the general ward among cohorts with SOFA scores of 2. The ICU group had lower in-hospital mortality than the HDU group among cohorts with SOFA scores greater than or equal to 12. There were no significant differences in in-hospital mortality among cohorts with SOFA scores 5–11. The ICU group had significantly higher in-hospital mortality than the general ward group among cohorts with SOFA scores less than or equal to 4.

CONCLUSIONS:

Patients hospitalized for sepsis with SOFA scores greater than or equal to 6 in the ICU or HDU had lower in-hospital mortality than those in the general ward, as did those with SOFA scores greater than or equal to 12 in the ICU versus HDU.
Current Research of Botulinum Toxin Type A in Prevention and Treatment on Pathological Scars
Authors: Wang Yi-Xin , Wang Yan , Zhang Qian , Zhang Run-Dong
Published: April 2023

BACKGROUND

Dermatologists have been looking for ways to improve wound healing and postoperative scar appearance. The safety and efficacy of botulinum toxin type A (BTXA) in the prevention and treatment on pathological scars have become the current research hotspot since it was approved by the US FDA in medical cosmetology in 2002.

PURPOSE

This article aims to provide an overview of the clinical research, limitations, and application prospects of BTXA in the prevention and treatment of traumatic or postoperative pathological scars, which can provide a reference and better understanding of relevant studies.

METHODS

The current research progress was summarized and discussed, with new problems and research ideas being proposed ranging from the molecular mechanism of BTXA in preventing and treating pathological scars to its clinical application via investigation and reference research.

RESULTS

BTXA is effective in relieving itching and pain associated with pathological scars, limiting scar hyperplasia along with preventing scar contracture, but the specific mechanism is still not clear.

CONCLUSION

Most of the clinicians have confirmed the clinical effectiveness of BTXA in the prevention and treatment of pathological scars, yet its mode of action and combination therapy need more research.
Efficacy and Safety of Extracellular Matrix on Wound Healing After Picosecond Laser Therapy
Authors: Li Anqi , Lin Xinwen , Mao Xuming , Sun Qiuning
Published: April 2023

BACKGROUND

Extracellular matrix (ECM), a material with tissue repair function, is applied to treat various wounds. However, the role of ECM in facilitating wound healing after facial laser treatment remains elusive.

OBJECTIVE

To assess the efficacy and safety of ECM in promoting wound healing after picosecond laser therapy (PLT).

MATERIALS AND METHODS

Eighteen female subjects with benign pigmentation disorders were randomly assigned to the ECM (n = 9) and control groups (n = 9). After PLT, the ECM and control groups were treated with ECM and facial moisturizer in the first 7 days, respectively. The severity of erythema and edema was assessed using photographs. The duration of erythema, edema, scab shedding, postinflammatory hyperpigmentation incidence (PIH), and adverse events was documented in detail.

RESULTS

Compared with the control group, the ECM group had a shorter duration of erythema, edema, and scab shedding after PLT (p < .01). A significantly decreased severity of erythema (p < .05) and edema (p < .01) was found in the ECM group versus the control group, respectively. The PIH incidence in the ECM group was lower than in controls, albeit without statistical significance. No serious adverse events were observed during the follow-up.

CONCLUSION

Extracellular matrix is an effective and safe dressing for promoting wound healing after PLT.
Multimodality cardiovascular imaging in hypertension
Authors: Dong Tiffany , Faaborg-Andersen Christian , Garcia Mariana , Blaha Michael , Klein Allan L. , Gill Edward , Quintana Raymundo A.
Published: April 2023

Purpose of the review

Hypertension accounts for the largest proportion of cardiovascular (CV) mortality worldwide and its prevalence continues to rise. While prominent CV societies have offered strong recommendations on the management of hypertension in adults, the role of noninvasive CV imaging in the evaluation of hypertensive patients remains incompletely defined.

Recent findings

Noninvasive imaging is a rapidly expanding field with a growing number of sophisticated and readily applicable modalities to assess how cardiac structure and function changes after periods of sustained, elevated blood pressure. Echocardiography remains the initial modality to screen these patients while developments in nuclear, computed tomography and cardiac magnetic resonance complement and expand investigations for alternative diagnoses that may complement or conflict with the diagnosis of left ventricular hypertrophy.

In this review article, we summarize the application of echocardiography, nuclear imaging, cardiac computed tomography, and cardiac magnetic resonance imaging in the evaluation and management of hypertensive heart disease.
Combination Therapy of Low-dose Steroids, Tacrolimus and Mycophenolate Mofetil in Primary Membranous Nephropathy: A Single-center Retrospective Cohort Study
Authors: Zhao Shujuan , Jia Lining , Cui Chenkai , Chen Zhao , Duan Zhaoyang , Gao Jie , Wei Linting , Xue Xiaodong , Lei Fuqian , Yang Yanyan , Liu Jing , Xu Peihao , Wang Rongrong , Wei Yang , Tian Xuefei , Fu Rongguo
Published: April 2023

Background:

Primary membranous nephropathy (pMN) is the most common pathological type of nephrotic syndrome in adults. Therefore, it is imperative to find a better combination therapy with fewer adverse effects for patients with pMN.

Methods:

This study enrolled 84 patients with biopsy-proven pMN and nephrotic syndrome. Thirty patients in the low-dose multitarget regimen (LDMT) group received low-dose glucocorticoids along with tacrolimus and mycophenolate mofetil, and 54 patients in the prednisone plus intravenous cyclophosphamide regimen (PC) group received corticosteroids plus intravenous cyclophosphamide. The clinical efficacy and safety of the LDMT and PC regimens in treating pMN in adults were analyzed and compared.

Results:

The cumulative complete remission rate was 6.67%, 56.30%, and 83.14% at the 6th, 12th, and 24th month after treatment in the LDMT group, and 16.67%, 60.84%, and 81.02% in the PC group, respectively (P = 0.620). The generalized estimating equation analysis showed that the longer the treatment duration, the better the improvements in serum albumin and urinary protein levels, and hyperlipidemia (P = 0.0001). However, the serum creatinine levels in both groups remained stable during the treatment period. Meanwhile, the relapse rates were comparable between the two groups (21.43% vs. 22.00%, P = 0.953). Moreover, patients in the LDMT group showed fewer adverse events than those in the PC group (46.67% vs. 72.22%, P = 0.020).

Conclusions:

These data indicated that the low-dose multitarget regimen, which might be an alternative treatment choice for patients with pMN, had a more favorable safety profile and non-inferior efficacy compared with prednisone plus intravenous cyclophosphamide.
Differential Diagnosis of Chronic Diarrhea
Authors: Brenner Darren M. , Domínguez-Muñoz J. Enrique
Published: April 2023

Chronic diarrhea, defined as diarrhea persisting for more than 4 weeks, affects up to 5% of the population regardless of patient age, sex, race, or socioeconomic status. The impact on patient health and quality of life is substantial, and diagnosis and management of these patients have significant economic consequences for health care services. The differential diagnosis of chronic diarrhea is broad, with etiologies including infections, endocrinopathies, maldigestive/malabsorptive conditions, and disorders of gut-brain interaction. The considerable overlap of symptoms across this spectrum makes accurate diagnosis problematic and may lead to delays in diagnosis or misdiagnosis. In this narrative review, we consider the differential diagnosis of chronic diarrhea, focusing on irritable bowel syndrome with diarrhea and exocrine pancreatic insufficiency, two conditions that may present similarly but have very different underlying causes and require significantly different management strategies. We outline a 4-step diagnostic strategy and propose a straightforward algorithm to assist in efficiently differentiating irritable bowel syndrome from exocrine pancreatic insufficiency and other causes of chronic diarrhea. We anticipate that these aids will improve diagnostic accuracy, which ultimately should lead to improvements in patients’ health-related quality of life and reduce the societal burden on health care services.
Comparison of efficacy according to voltage of pulsed radiofrequency treatment to lumbar dorsal root ganglion in patient with lumbar radiculopathy: Pilot study
Authors: Jang Jae Ni , Park Soyoon , Park Ji-Hoon , Song Yumin , Choi Sooil , Kim Young Uk , Park Sukhee
Published: April 2023

Background:

Lumbar radicular pain (LRP) is a common symptom, but a challenging clinical problem. Pulsed radiofrequency (PRF) is a more recently developed technique that uses short pulses of radiofrequency current with intervals of longer pauses to prevent temperature from rising to the level of permanent tissue damage and has been advocated in treatment of such patients. But there were no comparative studies on the analgesic effects according to output voltage during PRF in patients with LRP. The goal of this study is to determine the clinical effect of high-voltage (60V) versus standard-voltage (45V) PRF of lumbar dorsal root ganglion.

Methods/design:

This study will be a prospective, double-blind randomized controlled pilot study. In this study, total 20 patients will be recruited and distributed equally into 2 groups: high-voltage (60V) PRF, low-voltage (45V) PRF. Outcomes will be radicular pain intensity; physical functioning; global improvement and satisfaction with treatment; and adverse events. The assessments will be performed at the 3-month follow-up period after the end of the treatments. The findings will be analyzed statistically considering a 5% significance level (P ≤ .05).

Discussion:

The results of this trial will help determine which voltage could be applied for PRF to dorsal root ganglion in LRP and be a basis for subsequent trials.
Pulmonary function protection by single-port thoracoscopic segmental lung resection in elderly patients with IA non-small cell lung cancer: A differential matched analysis
Authors: Wang Silin , Shi Yonggang , Chen Heng , Xiong Jianwen , Zhang Xinle , Zhang Yelin , Zhu Kang , Yu Dongliang , Wei Yiping , Xiong Linmin
Published: April 2023

In patients with stage IA non-small cell lung cancer (NSCLC), uniportal video-assisted thoracic surgery (U-VATS) anatomical segmentectomy removes the lung tumor while preserving lung function as much as possible, and it is therefore an alternative to lobectomy. Patients with stage IA NSCLC receiving U-VATS segmental resection at our institution from September 2017 to June 2019 were compared with patients receiving U-VATS lobectomy. A total of 47 patients received segmentectomy and 209 patients received U-VATS lobectomy in the same period. Propensity score matching was conducted to diminish bias. The final study cohort included 42 patients who received segmentectomy and 42 propensity score matching-matched patients who received lobectomy. Perioperative parameters and postoperative complications, length of hospital stay, postoperative forced expiratory volume in 1 s (FEV1), and forced vital capacity (FVC) were compared between the 2 groups. Surgery was successfully completed in all patients. The mean follow-up was for 8.2 months. The postoperative complication rate was comparable between the 2 groups: 31.0% in segmentectomy patients versus 35.7% in lobectomy patients (P = .643). At 1 month after surgery, FEV1% and FVC% were not significantly different between the 2 groups (P > .05). At 3 months after surgery, FEV1 and FVC were higher in segmentectomy patients than in lobectomy patients (FEV1, 82.79% ± 6.36% vs 78.55% ± 5.42%; FVC, 81.66% ± 6.09% vs 78.90% ± 5.58%, P < .05). Patients receiving segmentectomy suffer less pain and have better postoperative lung function and higher quality of life.
Clinical Features of Children With Serology Negative, Biopsy Positive Celiac Disease
Authors: Bhattacharjee Amrita , Houlder Kieryn , Migliarese Isaac Daniela , Lacson Atilano , Turner Justine
Published: April 2023

The prevalence of pediatric serological negative celiac disease (SNCD) is poorly described, with few recognized clinical predictors beyond immunoglobulin A (IgA) deficiency or reduced gluten intake. The purpose of this retrospective review was to describe the prevalence of SNCD at the Stollery Children’s Hospital and identify clinical features to help in recognition of these cases. Patients with a positive biopsy and negative serology (SNCD) were compared to those with positive biopsy and serology. SNCD diagnosis required clinical correlation and either confirmatory genetics or follow up endoscopy on a gluten-free diet. Of the 424 patients who met celiac disease (CD) criteria, 4.7% (n = 20) fulfilled our criteria for SNCD. There was a significant difference in the rates of IgA deficiency between the 2 groups, but no other clinical features were found that allowed for ready identification of SNCD patients.
Emergency Severity Index Triage in Iran
Authors: Javidi Shima , Movahedi Mitra , Honarmand Amin , Mirafzal Amirhossein
Published: April 2023

There are concerns about the accuracy of Emergency Severity Index (ESI) triage system in the geriatric population. This study was performed to compare the correlation of ESI triage with injury severity score (ISS) between adults with trauma younger than 60 years and those 60 years of age and older and to determine the ability of ESI to predict an ISS of greater than 15 in these two age groups. This was an observational study performed in an academic trauma center in Kerman, Iran. A convenience sample of trauma patients older than 16 years was included. Five-level ESI triage was performed by nurses with 2–10 years of exclusive experience in triage. The ISS scores were calculated by the researchers. Both numerical and categorical (ISS >15) forms of the score were considered as outcomes. Ultimately, a total of 556 patients were enrolled in the study. No difference in undertriage was seen between the age groups (p = 0. 51). Spearman's correlation coefficient between ESI level and ISS was −0.69 and −0.77 in patients younger than 60 years and those aged 60 years or older, respectively (z = 1.20). The areas under the curves (AUCs) for prediction of ISS of greater than 15 were also similar between the two age groups (0.89 in less than 60 and 0.85 in 60 or more). In conclusion, the performance of ESI was similar between the two age groups. Therefore, the application of the ESI triage system for initial categorization of trauma patients seems to be a reliable and easy-to-learn method for the triage of elderly as well as younger age groups.
Postpartum Preeclampsia
Authors: Beck Cheryl Tatano
Published: April 2023

Postpartum preeclampsia has not received the needed attention that preeclampsia has. It is the lesser-known hypertensive disorder but can be just as life-threatening as eclampsia. Because of the scarcity of qualitative research on postpartum preeclampsia, the purpose of this study was to help fill this gap by exploring personal experiences of this dangerous complication as described in online blogs. Using Google search engine, 25 stories of postpartum preeclampsia were located. Krippendorff's content analysis for qualitative data was the research design used. Five themes were identified: (1) Not even on my radar as a new mom, (2) Bombarded with physical and emotional symptoms, (3) Life-threatening situation: Dismissed or misdiagnosed, (4) Heartbroken: Separation from my newborn, and (5) Trust your instincts and advocate for yourself. Advanced practice nurses and other health care providers need to be on alert for postpartum preeclampsia when a woman, who recently gave birth, presents at the emergency department.
Tissue and Cell Donation: Recommendations From an International Consensus Forum
Authors: Sánchez-Ibañez Jacinto , Humphreys Christine , Lomero Mar , Escoto Manuel , Weiss Matthew J. , Wilson Murray , López-Fraga Marta
Published: April 2023

Background.

Organ, tissue, and cell donation and transplantation legislation and policies vary substantially worldwide, as do performance outcomes in various jurisdictions. Our objective was to create expert, consensus guidance that links evidence and ethical concepts to legislative and policy reform for tissue and cell donation and transplantation systems.

Methods.

We identified topic areas and recommendations through consensus, using nominal group technique. The proposed framework was informed by narrative literature reviews and vetted by the project’s scientific committee. The framework was presented publicly at a hybrid virtual and in-person meeting in October 2021 in Montréal, Canada, where feedback provided by the broader Forum participants was incorporated into the final manuscript.

Results.

This report has 13 recommendations regarding critical aspects affecting the donation and use of human tissues and cells that need to be addressed internationally to protect donors and recipients. They address measures to foster self-sufficiency, ensure the respect of robust ethical principles, guarantee the quality and safety of tissues and cells for human use, and encourage the development of safe and effective innovative therapeutic options in not-for-profit settings.

Conclusions.

The implementation of these recommendations, in total or in part, by legislators and governments would benefit tissue transplantation programs by ensuring access to safe, effective, and ethical tissue- and cell-based therapies for all patients in need.
Pseudodesulfovibrio nedwellii sp. nov., a mesophilic sulphate-reducing bacterium isolated from a xenic culture of an anaerobic heterolobosean protist
Authors: Kondo Ryuji
Published: April 2023

A novel sulphate-reducing bacterium, strain SYKT, was isolated from a xenic culture of an anaerobic protist obtained from a sulphidogenic sediment of the saline Lake Hiruga in Fukui, Japan. The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that SYKT clustered with the members of the genus

Pseudodesulfovibrio

. The closest relative of strain SYKT was

Pseudodesulfovibrio sediminis

SF6T, with 16S rRNA gene sequence identity of 97.43 %. Digital DNA–DNA hybridisation and average nucleotide identity values between SYKT and species of the genus

Pseudodesulfovibrio

fell below the respective thresholds for species delineation, indicating that SYKT represents a novel species of the genus

Pseudodesulfovibrio

. Cells measured 1.7–3.7×0.2–0.5 µm in size and were Gram-stain-negative, obligately anaerobic, motile by means of a single polar flagellum and had a curved rod or sigmoid shape. Cell growth was observed under saline conditions from pH 6.0 to 9.5 (optimum pH 8.0–9.0) and at a temperature of 10–30 °C (optimum 25 °C). SYKT used lactate, pyruvate, fumarate, formate and H2 as electron donors. It used sulphate, sulphite, thiosulphate and sulphur as terminal electron acceptors. Pyruvate and fumarate were fermented. Major cellular fatty acids were anteiso-C15 : 0, C16 : 0, anteiso-C17 : 1ω9c, summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c) and summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c). The DNA G+C content of SYKT was 49.4 mol%. On the basis of the the genetic and phenotypic features, SYKT was determined to represent a novel species of the genus

Pseudodesulfovibrio

for which the name Pseudodesulfovibrio nedwellii sp. nov. is proposed with type strain SYKT (=DSM 114958T=JCM 35746T).
InVitroBiocompatibility Evaluation of Acellular Porcine Dura mater Grafts and Native Dura
Authors: Sharma Ashma , Moore Erika , Williams Lakiesha N.
Published: April 2023

Damage to the dura mater may occur during intracranial or spinal surgeries, which can result in cerebrospinal fluid leakage as well as other potentially fatal physiological changes. As a result, biological scaffolds derived from xenogeneic materials are typically used to repair and regenerate dura mater post intracranial or spinal surgeries. The extracellular matrix of xenogeneic dura scaffolds has been shown to exhibit better cell infiltration and regeneration than synthetic material. In this study, we investigated the biocompatibility of native and decellularized porcine dura. Cell proliferation, cell viability, and mechanical properties of dural grafts were evaluated post re-seeding on days 3,7, and 14. Live-dead staining and resazurin salts were used to quantify cell viability and cell proliferation, respectively. Micro indentation was conducted to quantify the mechanical integrity of the native and acellular dura graft. The results show that the acellular porcine dural graft provides a favorable environment for rat fibroblast cell infiltration. Cell viability, proliferation, and micro indentation results on the acellular grafts are comparable with the native control porcine dura tissue. In conclusion, the porcine scaffold material showed increasing viable cells at each time point. The mechanics and biocompatibility results provide promising insight into the potential use of porcine dura in future cranial dura mater graft applications.
Orthogonal axes of microbiome variation associated with functionally distinct transcriptomic signatures in the gut of wildDrosophila melanogaster
Authors: Llanwarne Frances , Dobson Adam J
Published: April 2023

Gut microbiota are fundamental for healthy animal function, but the evidence that host function can be predicted from microbiota taxonomy remains equivocal, and natural populations remain understudied compared to laboratory animals. Paired analyses of covariation in microbiota and host parameters are powerful approaches to characterise host-microbiome relationships mechanistically, especially in wild populations of animals that are also lab models, enabling insight into the ecological basis of host function at a molecular and cellular level. The fruitflyDrosophila melanogasteris a preeminent model organism, amenable to field investigation by’omic analyses. Here we present an analysis of wild maleD. melanogaster, with paired measurements of (A) bacterial diversity and abundance, measured by 16S amplicon sequencing; and (B) the host gut transcriptome. We found orthogonal axes of microbial genera, which correspond to differential expression of host genes. The differentially-expressed gene sets were enriched in functions including protein translation, mitochondrial respiration, immunity and reproduction. Each gene set had a distinct functional signature, suggesting that wild flies exhibit a range of distinct axes of functional variation, which correspond to orthogonal axes of microbiome variation. These findings strengthen the bridge between the wild ecology and functional genetics of a leading host-microbiome model.
Metabolic Reprogramming by Histone Deacetylase Inhibition Selectively Targets NRF2-activated tumors
Authors: Karagiannis Dimitris , Wu Warren , Li Albert , Hayashi Makiko , Chen Xiao , Yip Michaela , Mangipudy Vaibhav , Xu Xinjing , Sánchez-Rivera Francisco J. , Soto-Feliciano Yadira M. , Ye Jiangbin , Papagiannakopoulos Thales , Lu Chao
Published: April 2023

Interplay between metabolism and chromatin signaling have been implicated in cancer initiation and progression. However, whether and how metabolic reprogramming in tumors generates specific epigenetic vulnerabilities remain unclear. Lung adenocarcinoma (LUAD) tumors frequently harbor mutations that cause aberrant activation of the NRF2 antioxidant pathway and drive aggressive and chemo-resistant disease. We performed a chromatin-focused CRISPR screen and report that NRF2 activation sensitized LUAD cells to genetic and chemical inhibition of class I histone deacetylases (HDAC). This association was consistently observed across cultured cells, syngeneic mouse models and patient-derived xenografts. HDAC inhibition causes widespread increases in histone H4 acetylation (H4ac) at intergenic regions, but also drives re-targeting of H4ac reader protein BRD4 away from promoters with high H4ac levels and transcriptional downregulation of corresponding genes. Integrative epigenomic, transcriptomic and metabolomic analysis demonstrates that these chromatin changes are associated with reduced flux into amino acid metabolism andde novonucleotide synthesis pathways that are preferentially required for the survival of NRF2-active cancer cells. Together, our findings suggest that metabolic alterations such as NRF2 activation could serve as biomarkers for effective repurposing of HDAC inhibitors to treat solid tumors.
Protein homeostasis from diffusion-dependent control of protein synthesis and degradation
Authors: Chen Yuping , Huang Jo-Hsi , Phong Connie , Ferrell James E.
Published: April 2023

It has been proposed that the concentration of proteins in the cytoplasm maximizes the speed of important biochemical reactions. Here we have used theXenopusextract system, which can be diluted or concentrated to yield a range of cytoplasmic protein concentrations, to test the effect of cytoplasmic concentration on mRNA translation and protein degradation. We found that protein synthesis rates are maximal in ∼1x cytoplasm, whereas protein degradation continues to rise to an optimal concentration of ∼1.8x. This can be attributed to the greater sensitivity of translation to cytoplasmic viscosity, perhaps because it involves unusually large macromolecular complexes like polyribosomes. The different concentration optima sets up a negative feedback homeostatic system, where increasing the cytoplasmic protein concentration above the 1x physiological level increases the viscosity of the cytoplasm, which selectively inhibits translation and drives the system back toward the 1x set point.
Sizes, conformational fluctuations, and SAXS profiles for Intrinsically Disordered Proteins
Authors: Mugnai Mauro L. , Chakraborty Debayan , Kumar Abhinaw , Nguyen Hung T. , Zeno Wade , Stachowiak Jeanne C. , Straub John E. , Thirumalai D.
Published: April 2023

The preponderance of Intrinsically Disordered Proteins (IDPs) in the eukaryotic proteome, and their ability to interact with each other, folded proteins, RNA, and DNA for functional purposes, have made it important to quantitatively characterize their biophysical properties. Toward this end, we developed the transferable Self-Organized Polymer (SOP-IDP) model to calculate the properties of several IDPs. The values of the radius of gyration (Rg) obtained from SOP-IDP simulations are in excellent agreement (correlation coefficient of 0.96) with those estimated from SAXS experiments. For AP180 and Epsin, the predicted values of the hydrodynamic radii (Rhs) are in quantitative agreement with those from Fluorescence Correlation Spectroscopy (FCS) experiments. Strikingly, the calculated SAXS spectra for thirty-six IDPs are also nearly superimposable on the experimental profiles. The dependence ofRgand the mean end-to-end distance (Ree) on chain length,N, follows Flory’s scaling law,Rα≈aαN0.588(α=g, ande), suggesting that globally IDPs behave as synthetic polymers in a good solvent. The values ofag, andaeare 0.20 nm and 0.48 nm respectively. Surprisingly, finite size corrections to scaling, expected on theoretical grounds, are negligible forRgandRee. In contrast, only by accounting for the finite sizes of the IDPs, the dependence of experimentally measurableRhonNcan be quantitatively explained usingν= 0.588. Although Flory scaling law captures the estimates forRg,Ree, andRhaccurately, the spread of the simulated data around the theoretical curve is suggestive of of sequence-specific features that emerge through a fine-grained analysis of the conformational ensembles using hierarchical clustering. Typically, the ensemble of conformations partitiones into three distinct clusters, having different equilibrium populations and structural properties. Without any further readjustments to the parameters of the SOP-IDP model, we also obtained excellent agreement with paramagnetic relaxation enhancement (PRE) measurements forα-synuclein. The transferable SOP-IDP model sets the stage for several applications, including the study of phase separation in IDPs and interactions with nucleic acids.
Interpretable dimensionality reduction and classification of mass spectrometry imaging data in a visceral pain model via non-negative matrix factorization
Authors: Pathirage Kasun , Virmani Aman , Scott Alison J. , Traub Richard J. , Ernst Robert K. , Ghodssi Reza , Babadi Behtash , Abshire Pamela
Published: April 2023

Mass spectrometry imaging (MSI) is a powerful scientific tool for understanding the spatial distribution of biochemical compounds in tissue structures. MSI data analysis presents problems due to the large file sizes and computational resource requirements and also due to the complexity of interpreting the raw spectral data. Dimensionality reduction techniques that address the first issue do not necessarily result in readily interpretable features. In this paper, we present non-negative matrix factorization (NMF) as a dimensionality reduction algorithm that reduces the size of MSI datasets by three orders of magnitude with limited loss of information, yielding spatial and spectral components with meaningful correlation to tissue structure. This analysis is demonstrated on an MSI dataset from female Sprague-Dawley rats for an animal model of comorbid visceral pain hypersensitivity (CPH). The significant findings are: 1) High-dimensional MSI data (∼100,000 ions per pixel) was reduced to 20 spectral NMF components with<20% loss in reconstruction accuracy. 2) Spatial NMF components are reproducible and correlate well with H&E-stained tissue images. 3) Spatial NMF components may be used to provide images with enhanced specificity for different tissue types. 4) Small patches of NMF data (i.e., 20 spatial NMF components over 20 x 20 pixels) provide an accuracy of∼87% in classifying CPH vs näıve control subjects. This paper presents novel methodologies for data augmentation to support classification, ranking of features according to their contribution to classification, and image registration to support tissue-specific imaging.
How do host population dynamics impact Lyme disease risk dynamics in theoretical models?
Authors: Savage Joseph D.T. , Moore Christopher M.
Published: April 2023

Lyme disease is the most common wildlife-to-human transmitted disease reported in North America. The study of this disease requires an understanding of the ecology of the complex communities of ticks and host species involved in harboring and transmitting this disease. Much of the ecology of this system is well understood, such as the life cycle of ticks, and how hosts are able to support tick populations and serve as disease reservoirs, but there is much to be explored about how the population dynamics of different host species and communities impact disease risk to humans. In this study we construct a stage-structured, empirically-informed model with host dynamics to investigate how host population dynamics can affect disease risk to humans. The model describes a tick population and a simplified community of three host species, where primary nymph host populations are made to fluctuate on an annual basis, as commonly observed in host populations. We tested the model under different environmental conditions to examine the effect of environment on the interactions of host dynamics and disease risk. Results show that allowing for host dynamics in the model reduces mean nymphal infection prevalence and increases the maximum annual prevalence of nymphal infection and the density of infected nymphs. Effects of host dynamics on disease measures of nymphal infection prevalence were nonlinear and patterns in the effect of dynamics on amplitude in nymphal infection prevalence varied across environmental conditions. These results highlight the importance of further study of the effect of community dynamics on disease risk. This will involve the construction of further theoretical models and collection of robust field data to inform these models With a more complete understanding of disease dynamics we can begin to better determine how to predict and manage disease risk using these models.
CcBHLA: pan-specific peptide–HLA class I binding prediction via Convolutional and BiLSTM features
Authors: Wu Yejian , Cao Lujing , Wu Zhipeng , Wu Xinyi , Wang Xinqiao , Duan Hongliang
Published: April 2023

Human major histocompatibility complex (MHC) proteins are encoded by the human leukocyte antigen (HLA) gene complex. When exogenous peptide fragments form peptide-HLA (pHLA) complexes with HLA molecules on the outer surface of cells, they can be recognized by T cells and trigger an immune response. Therefore, determining whether an HLA molecule can bind to a given peptide can improve the efficiency of vaccine design and facilitate the development of immunotherapy. This paper regards peptide fragments as natural language, we combine textCNN and BiLSTM to build a deep neural network model to encode the sequence features of HLA and peptides. Results on independent and external test datasets demonstrate that our CcBHLA model outperforms the state-of-the-art known methods in detecting HLA class I binding peptides. And the method is not limited by the HLA class I allele and the length of the peptide fragment. Users can download the model for binding peptide screening or retrain the model with private data on github (https://github.com/hongliangduan/CcBHLA-pan-specific-peptide-HLA-class-I-binding-prediction-via-Convolutional-and-BiLSTM-features.git).
Perfusion estimation using MRI-based measurements and a porous media flow model
Authors: Lorentzen Rolf J. , Nævdal Geir , Sævareid Ove , Hodneland Erlend , Hanson Erik , Munthe-Kaas Antonella Z.
Published: April 2023

The measurement of perfusion and filtration of blood in biological tissue give rise to important clinical parameters used in diagnosis, follow-up, and therapy. In this paper we address techniques for perfusion analysis using processed contrast agent concentration data from dynamic MRI acquisitions. New methodology for analysis is evaluated and verified using synthetic data generated on a tissue geometry.

Author summary

Accurate knowledge of tissue perfusion is crucial for proper diagnostics and treatment of several medical disorders. Traditional methods based on medical imaging are fast, but usually lack precision and robustness. In this paper, we address methodology to develop better diagnosis and treatment strategies for malignant tumors and stroke where blood perfusion may be altered. In our work, mathematical models for estimating perfusion are calibrated using magnetic resonance imaging (MRI) data, and more accurate representations of tissue parameters are provided. This methodology is a step towards minimal invasive and individually tailored diagnosis and treatment. We demonstrate the methodology with a twin-experiment using models of different complexity for generating data and estimating the tissue parameters. Both models are based on a mathematical description of how fluids flows in a porous medium, where the data-generating model uses higher resolution and a network representation of blood vessels than the estimating model. The calibration of unknown tissue parameters is done using a statistical framework, and the choice of methodology is motivated by applications from sub-surface reservoir characterization.
Interdependence of primary and secondary somatosensory cortices for plasticity and texture discrimination learning
Authors: Pandey Anurag , Kang Sungmin , Pacchiarini Nicole , Wyszynska Hanna , Grewal Aneesha , Griffiths Alex , Healy-Millett Imogen , Masseri Zena , Hardingham Neil , O’Neill Joseph , Honey Robert C. , Fox Kevin
Published: April 2023

Feedforward and feedback pathways are important for transfer and integration of information between sensory cortical areas. Here we find that two closely connected cortical areas, the primary (S1) and secondary somatosensory cortices (S2) are both required for mice to learn a whisker-dependent texture discrimination. Increased inhibition in either area (using excitatory DREADDs expressed in inhibitory interneurones) prevents learning. We find that learning the discrimination produces structural plasticity of dendritic spines on layer 2/3 pyramidal neurones in vibrissae S1 that is restricted to the basal dendrites and leaves dendritic spines on apical dendrites unchanged. As S2 projects to the apical dendrites of S1 neurones, we tested whether S2 affects LTP-induction in S1. We found that feedback projections from S2 to S1 gates LTP on feedforward pathways within S1. These studies therefore demonstrate the interdependence of S1 and S2 for learning and plasticity in S1.

HIGHLIGHTS

Both primary (S1) and secondary (S2) somatosensory cortices are necessary for whisker based texture discrimination learning

S2 feedback connections to S1 gate LTP at feedforward pathways in S1

S1 undergoes structural plasticity of pre-existing spines during learning

S1 learning induced plasticity and LTP occurs on basal but not apical dendrites
Development and Mobile Deployment of a Stair Recognition System for Human-Robot Locomotion
Authors: Kurbis Andrew Garrett , Mihailidis Alex , Laschowski Brokoslaw
Published: April 2023

Environment sensing and recognition can improve the safety and autonomy of human-robot locomotion, especially during transitions between environmental states such as walking to and from stairs. However, accurate and real-time perception on edge devices with limited computational resources is an open problem. Here we present the development and mobile deployment ofStairNet- a vision-based automated stair recognition system powered by deep learning. Building onExoNet- the largest open-source dataset of egocentric images of real-world walking environments - we designed a new dataset specifically for stair recognition with over 515,000 images. We then developed a lightweight and efficient convolutional neural network for image classification, which accurately predicted complex stair environments with 98.4% accuracy. We also studied different model compression and optimization methods and deployed our system on several mobile devices running a custom-designed iOS application with onboard accelerators using CPU, GPU, and/or NPU backend computing. Of the designs that we tested, our highest performing system showed negligible reductions in classification accuracy due to the model conversion for mobile deployment and achieved an inference time of 2.75 ms on an iPhone 11. The high speed and accuracy of theStairNetsystem on edge devices opens new opportunities for autonomous control and planning of robotic prosthetic legs, exoskeletons, and other assistive technologies for human locomotion.
Unlocking the Secrets of the Primate Visual Cortex: A CNN-Based Approach Traces the Origins of Major Organizational Principles to Retinal Sampling
Authors: da Costa Danny , Kornemann Lukas , Goebel Rainer , Senden Mario
Published: April 2023

Primate visual cortex exhibits key organizational principles: Cortical magnification, eccentricity-dependent receptive field size and spatial frequency tuning as well as radial bias. We provide compelling evidence that these principles arise from the interplay of the non-uniform distribution of retinal ganglion cells (RGCs), and a quasi-uniform convergence rate from the retina to the cortex. We show that convolutional neural networks (CNNs) outfitted with a retinal sampling layer, which resamples images according to retinal ganglion cell density, develop these organizational principles. Surprisingly, our results indicate that radial bias is spatial-frequency dependent and only manifests for high spatial frequencies. For low spatial frequencies, the bias shifts towards orthogonal orientations. These findings introduce a novel hypothesis about the origin of radial bias. Quasi-uniform convergence limits the range of spatial frequencies (in retinal space) that can be resolved, while retinal sampling determines the spatial frequency content throughout the retina.
Robust detection of clinically relevant features in single-cell RNA profiles of patient-matched fresh and formalin-fixed paraffin-embedded (FFPE) lung cancer tissue
Authors: Trinks Alexandra , Milek Miha , Beule Dieter , Kluge Julie , Florian Stefan , Sers Christine , Horst David , Morkel Markus , Bischoff Philip
Published: April 2023

Single-cell transcriptional profiling reveals cell heterogeneity and clinically relevant traits in intra-operatively collected patient-derived tissue. However, the established approach to perform such analyses on freshly collected tissue constitutes an important limitation since it requires prospective collection and immediate processing. Therefore, the ability to perform single-cell RNA sequencing from archived tissues would be very beneficial in a clinical setting. Here, we benchmark single-cell gene expression profiles from patient-matched fresh, cryopreserved and FFPE cancer tissue. We find that fresh tissue and FFPE routine blocks can be employed for the robust detection of clinically relevant traits on the single-cell level. Specifically, single-cell maps of fresh patient tissues and corresponding FFPE tissue blocks could be integrated into common low-dimensional representations, and cell subtype clusters showed highly correlated transcriptional strengths of signaling pathways, Hallmark and clinically useful signatures, despite some variability in expression of individual genes due to technological differences. FFPE tissue blocks revealed higher cell diversity compared to fresh tissue. In contrast, single-cell profiling of cryopreserved tissue was prone to artifacts in the clinical setting. Our analysis suggests that single-cell RNA sequencing from FFPE tissues is comparable to and can replace analyses from fresh tissue. This highlights the potential of single-cell profiling in the analysis of retrospectively and prospectively collected archival pathology cohorts and dramatically increases the applicability in translational projects.
Leaf excision has minimal impact on photosynthetic parameters across crop functional types
Authors: Ferguson John N. , Jithesh Tamanna , Lawson Tracy , Kromdijk Johannes
Published: April 2023

Photosynthesis is increasingly becoming a recognised target for crop improvement. Phenotyping photosynthesis-related traits on field-grown material is a key bottleneck to progress here due to logistical barriers and short measurement days. Many studies attempt to overcome these challenges by phenotyping excised leaf material in the laboratory. To date there are no demonstrated examples of the representative nature of photosynthesis measurements performed on excised leaves relative to intact leaves in crops. Here, we tested whether standardised leaf excision on the day prior to phenotyping impacted a range of common photosynthesis-related traits across crop functional types using tomato (C3-dicot), barley (C3-monocot), and maize (C4-monocot). Potentially constraining aspects of leaf physiology that could be forecasted to impair photosynthesis in excised leaves, namely leaf water potential and abscisic acid accumulation, were not different between intact and excised leaves. We also observed non-significant differences in spectral reflectance and chlorophyll fluorescence traits between the treatments across the three species. However, we did observe some significant differences between gas exchange and photosynthetic capacity associated traits across all three species. This study represents a useful reference for those who perform measurements of this nature and the differences reported should be considered in associated experimental design and statistical analyses.

Highlight

Across the main photosynthesis functional types (C3-dicot, C3-monot, and C4-monot) of major crops (tomato, barley, and maize), measurements of photosynthetic parameters demonstrate few, but important, differences when measured on excised relative to intact leaves.
Tegument ultrastructure in mother sporocysts ofBunocotyle progenetica(Markowski, 1936) Chabaud & Buttner, 1959 (Digenea: Hemiuridae)
Authors: Podvyaznaya I.M. , Filimonova S.A.
Published: April 2023

This investigation is devoted to the fine structure of mother sporocysts, the least studied stage of the digenean life cycle. The ultrastructure of the tegument of mature mother sporocysts ofBunocotyle progeneticawas examined by transmission electron microscopy and described in detail. The tegument of these parthenitae is represented by an outer anucleate syncytium connected with the deeper-lying tegumental cells by cytoplasmic bridges. Its outer plasma membrane forms minute leaf-like outgrowths and numerous deep invaginations in the shape of interconnected channels. These channels, which pass in various directions and permeate almost the entire outer syncytium, considerably amplify its surface area. The cytoplasm of the outer layer of the tegument contains large mitochondria, microtubules and rare dense secretory granules, whose contents are discharged into the lumen of the channels. Numerous pinocytotic vesicles originate from the plasma membrane of the channels. Small endocytic vesicles are transported along the cytoplasmic bridges to the tegumental cells, where endocytosed food material is sorted and broken down. These cells are characterized by a well-developed Golgi apparatus, which is represented by multiple stacks of cisternae, and the presence of numerous endosomes at different stages of maturity and residual bodies. Some steps of endosomal maturation in the tegumental cells were traced. In addition to their digestive activity, tegumental cells produce secretory granules, which are transported to the outer syncytium after their maturation. It was shown for the first time that in mature parthenitae, the population of tegumental cells could be renewed at the expense of a reserve pool of undifferentiated cells. The ultrastructural features of the tegument of mother sporocysts ofB. progeneticaare discussed in the light of the concept of the enhanced trophic function of the tegument in sporocysts lacking the alimentary canal.