bluuebunny/crossref_metadata_2025 huggingface dataset:
Feasibility, effectiveness, and acceptability of an afternoon-evening sleep schedule in older nightshift workers
Authors: Barger Laura K , Zhang Yuan , Lammers-van der Holst Heidi M , Snoep Davina , Murphy Audra S , Desnoyers Brian , Duffy Jeanne F
Published: February 2024

Study Objectives

To explore the feasibility, effectiveness, and acceptability of an afternoon-evening sleep schedule in older (age 50–65 years) nightshift workers.

Methods

We used a three-part strategy: a screening survey to identify individuals who said they could adopt an 8-hour afternoon-evening sleep schedule; a field study where daily diary and actigraphy data were collected during a baseline week and intervention week, with randomization to self-selected sleep, 8-hour afternoon-evening time in bed (TIB), or 8-hour self-selected TIB; and follow-up focus groups to understand the acceptability of the intervention.

Results

Gender (p < 0.001), Hispanic ethnicity (p = 0.023), the care of children (p = 0.014), and chronotype (p = 0.012), predicted the reported ability to spend 8 hours in bed in the afternoon-evening. Participants assigned to the 8-hour self-selected and 8-hour afternoon-evening groups significantly increased their TIB and sleep duration compared to baseline (p < 0.05), while the control group did not. Although spending 8 hours in bed was feasible for the participants during the study, focus group discussions indicated participants would not continue an 8-hour TIB schedule after the study due to family responsibilities and other activities of daily living.

Conclusions

Spending 8 hours in bed between successive night shifts, initiated at both a self-selected time and in the afternoon-evening, increased the sleep duration of older shiftworkers, but most would not continue such a schedule on their own. Additional research is needed to find countermeasures for the reduced sleep duration experienced by most shiftworkers that are not only effective, but also compatible with shiftworkers’ lifestyles.
Label-Free and High-Throughput Removal of Residual Undifferentiated Cells From iPSC-Derived Spinal Cord Progenitor Cells
Authors: Nguyen Tan Dai , Chooi Wai Hon , Jeon Hyungkook , Chen Jiahui , Tan Jerome , Roxby Daniel N , Lee Cheryl Yi-Pin , Ng Shi-Yan , Chew Sing Yian , Han Jongyoon
Published: February 2024

The transplantation of spinal cord progenitor cells (SCPCs) derived from human-induced pluripotent stem cells (iPSCs) has beneficial effects in treating spinal cord injury (SCI). However, the presence of residual undifferentiated iPSCs among their differentiated progeny poses a high risk as these cells can develop teratomas or other types of tumors post-transplantation. Despite the need to remove these residual undifferentiated iPSCs, no specific surface markers can identify them for subsequent removal. By profiling the size of SCPCs after a 10-day differentiation process, we found that the large-sized group contains significantly more cells expressing pluripotent markers. In this study, we used a sized-based, label-free separation using an inertial microfluidic-based device to remove tumor-risk cells. The device can reduce the number of undifferentiated cells from an SCPC population with high throughput (ie, >3 million cells/minute) without affecting cell viability and functions. The sorted cells were verified with immunofluorescence staining, flow cytometry analysis, and colony culture assay. We demonstrated the capabilities of our technology to reduce the percentage of OCT4-positive cells. Our technology has great potential for the “downstream processing” of cell manufacturing workflow, ensuring better quality and safety of transplanted cells.
Statistics support and anxiety explored
Authors: Marshall Ellen , Riach Anna , Shaker Amanda , Rowlett Peter
Published: February 2024

Most higher education institutions in the UK now offer some form of additional individual support for mathematics and statistics. Whilst numerous studies have shown mathematics support can improve grades and reduce failure rates, there is a lack of research on other outcomes of interest such as anxiety or confidence, and very little research relating specifically to statistics support. This study uses quantitative and qualitative results from student questionnaires to evaluate the effectiveness of support in reducing anxiety and increasing confidence immediately after the first statistics support session and in the longer term. Comparisons of and preferences for online or face-to-face sessions and other aspects relating to anxiety were also explored. Key quantitative findings include a significant reduction in statistics anxiety after only one session of statistics support and a long-term increase in confidence with statistics. When asked how support impacts on anxiety or confidence, key themes emerging included feeling comfortable asking questions in statistics support, tailoring to individual needs and confirmation of understanding. The majority of students preferred face-to-face sessions over online particularly those with higher levels of statistics anxiety. Although differences were generally not significant, higher levels of anxiety were observed before online sessions and greater changes in anxiety occurred during face-to-face sessions.
Study on SH-SY5Y autophagy inhibition and apoptosis induced by methanol extract of Zanthoxylum armatum DC. based on mTOR signal pathway
Authors: Guo Jiafu , Wen Jiayu , Xiang Qiwen , Huang Yan , Hu Tingting , Rao Chaolong
Published: February 2024

Background

Zanthoxylum armatum DC. (ZADC) is a novel food raw material resource, offering both edible and medicinal properties. Recent research has unveiled the toxic nature of ZADC, particularly its close association with the nervous system. In a prior study, we observed that administering methanol extract of Zanthoxylum armatum DC. (MZADC) to rats via gavage at a dose of 1.038 g/kg resulted in various neurotoxicity symptoms, including excessive salivation, reduced mobility, unsteady gait, muscle twitching, and altered respiratory rates.

Materials and methods

We conducted cell-based research to assess the safety of ZADC and elucidate its potential toxic mechanism. In addition, we used experimental methods such as Cell Counting Kit-8, Western blot, and Flow cytometry to detect cytotoxicity in SH-SY5Y cells after intervention with MZADC.

Results

Following exposure of SY-SY5Y cells with MZADC, a substantial decline in cell viability was observed, accompanied by a concentration-dependent increase in intracellular reactive oxygen species (ROS) levels. Additionally, MZADC induced cellular oxidative stress, leading to elevated malonic dialdehyde (MDA) and superoxide dismutase (SOD) concentrations while decreasing glutathione (GSH) levels. Furthermore, MZADC induced apoptosis at varying doses (20, 40, and 60 μg/mL), and this effect was associated with increased Caspase-3, Bax expressions, and reduced Bcl2 and Bcl2/Bax expressions. In addition, the investigation revealed that MZADC induced autophagy inhibition in SH-SY5Y cells by activating the mTOR signaling pathway, resulting in a decrease in LC3II/LCI and Beclin-1, while increasing p-mTOR/mTOR, p62.

Conclusion

Consequently, this study suggests that MZADC triggers the mTOR pathway through oxidative stress in SH-SY5Y cells, ultimately leading to apoptosis. Understanding the toxicity mechanisms associated with ZADC can offer a valuable theoretical and experimental basis for its development and utilization.
Functional consequences of familial ALS‐associated SOD1L84F in neuronal and muscle cells
Authors: Verma Sagar , Vats Abhishek , Ahuja Vanshika , Vats Kavita , Khurana Shiffali , Vats Yuvraj , Gourie‐Devi Mandaville , Wajid Saima , Ganguly Nirmal Kumar , Chakraborti Pradip , Taneja Vibha
Published: February 2024

Amyotrophic lateral sclerosis is a fatal neurodegenerative disorder characterized by progressive skeletal muscle denervation and loss of motor neurons that results in muscle atrophy and eventual death due to respiratory failure. Previously, we identified a novel SOD1L84F variation in a familial ALS case. In this study, we examined the functional consequences of SOD1L84F overexpression in the mouse motor neuron cell line (NSC‐34). The cells expressing SOD1L84F showed increased oxidative stress and increased cell death. Interestingly, SOD1L84F destabilized the native dimer and formed high molecular weight SDS‐resistant protein aggregates. Furthermore, SOD1L84F also decreased the percentage of differentiated cells and significantly reduced neurite length. A plethora of evidence suggested active involvement of skeletal muscle in disease initiation and progression. We observed differential processing of the mutant SOD1 and perturbations of cellular machinery in NSC‐34 and muscle cell line C2C12. Unlike neuronal cells, mutant protein failed to accumulate in muscle cells probably due to the activated autophagy, as evidenced by increased LC3‐II and reduced p62. Further, SOD1L84F altered mitochondrial dynamics only in NSC‐34. In addition, microarray analysis also revealed huge variations in differentially expressed genes between NSC‐34 and C2C12. Interestingly, SOD1L84F hampered the endogenous FUS autoregulatory mechanism in NSC‐34 by downregulating retention of introns 6 and 7 resulting in a two‐fold upregulation of FUS. No such changes were observed in C2C12. Our findings strongly suggest the differential processing and response towards the mutant SOD1 in neuronal and muscle cell lines.
Integrated causal inference modeling uncovers novel causal factors and potential therapeutic targets of Qingjin Yiqi granules for chronic fatigue syndrome
Authors: Li Junrong , Zhai Xiaobing , Liu Jixing , Lam Chi Kin , Meng Weiyu , Wang Yuefei , Li Shu , Wang Yapeng , Li Kefeng
Published: February 2024

Objective:

Chronic fatigue syndrome (CFS) is a prevalent symptom of post-coronavirus disease 2019 (COVID-19) and is associated with unclear disease mechanisms. The herbal medicine Qingjin Yiqi granules (QJYQ) constitute a clinically approved formula for treating post-COVID-19; however, its potential as a drug target for treating CFS remains largely unknown. This study aimed to identify novel causal factors for CFS and elucidate the potential targets and pharmacological mechanisms of action of QJYQ in treating CFS.

Methods:

This prospective cohort analysis included 4,212 adults aged ≥65 years who were followed up for 7 years with 435 incident CFS cases. Causal modeling and multivariate logistic regression analysis were performed to identify the potential causal determinants of CFS. A proteome-wide, two-sample Mendelian randomization (MR) analysis was employed to explore the proteins associated with the identified causal factors of CFS, which may serve as potential drug targets. Furthermore, we performed a virtual screening analysis to assess the binding affinity between the bioactive compounds in QJYQ and CFS-associated proteins.

Results:

Among 4,212 participants (47.5% men) with a median age of 69 years (interquartile range: 69–70 years) enrolled in 2004, 435 developed CFS by 2011. Causal graph analysis with multivariate logistic regression identified frequent cough (odds ratio: 1.74, 95% confidence interval [CI]: 1.15–2.63) and insomnia (odds ratio: 2.59, 95% CI: 1.77–3.79) as novel causal factors of CFS. Proteome-wide MR analysis revealed that the upregulation of endothelial cell-selective adhesion molecule (ESAM) was causally linked to both chronic cough (odds ratio: 1.019, 95% CI: 1.012–1.026, P = 2.75 e−05) and insomnia (odds ratio: 1.015, 95% CI: 1.008–1.022, P = 4.40 e−08) in CFS. The major bioactive compounds of QJYQ, ginsenoside Rb2 (docking score: −6.03) and RG4 (docking score: −6.15), bound to ESAM with high affinity based on virtual screening.

Conclusions:

Our integrated analytical framework combining epidemiological, genetic, and in silico data provides a novel strategy for elucidating complex disease mechanisms, such as CFS, and informing models of action of traditional Chinese medicines, such as QJYQ. Further validation in animal models is warranted to confirm the potential pharmacological effects of QJYQ on ESAM and as a treatment for CFS.
Caffeine Ameliorates Age-Related Hearing Loss by Downregulating the Inflammatory Pathway in Mice
Authors: Zhang Xiaolin , Cao Ruijuan , Li Changye , Zhao Hongchun , Zhang Ruyi , Che Juan , Xie Jinwen , Tang Na , Wang Yanfei , Liu Xiuzhen , Zheng Qingyin
Published: February 2024

Objective

Age-related hearing loss (ARHL), also known as presbycusis, is a debilitating sensory impairment that affects the elderly population. There is currently no ideal treatment for ARHL. Long-term caffeine intake was reported to have anti-aging effects in many diseases. This study is to identify whether caffeine could ameliorate ARHL in mice and analyze its mechanism.

Methods

Caffeine was administered in drinking water to C57BL/6J mice from the age of 3 months to 12 months. The body weight, food intake and water intake of the mice were monitored during the experiment. The metabolic indicators of serum were detected by ELISA. The function of the hearing system was evaluated by ABR and hematoxylin and eosin staining of the cochlea. Genes' expression were detected by Q-PCR, immunofluorescencee and Western blot.

Results

The results showed that the ARHL mice exhibited impaired hearing and cochlear tissue compared with the young mice. However, the caffeine-treated ARHL mice showed improved hearing and cochlear tissue morphology. The expression of inflammation-related genes, such as TLR4, Myd88, NF-κB, and IL-1β, was significantly increased in the cochleae of ARHL mice compared with young mice but was down-regulated in the caffeine-treated cochleae.

Conclusions

Inflammation is involved in ARHL of mice, and long-term caffeine supplementation could ameliorate ARHL through the down-regulation of the TLR4/NF-κB inflammation pathway. Our findings provide a new idea for preventing ARHL and suggest new drug targets for ARHL treatment.
Fitness and walking outcomes following aerobic and lower extremity strength training in facioscapulohumeral dystrophy: a case series
Authors: Prieur-Blanc Nicolas , Cotinat Maëva , Vansteenkiste Sebastien , de Bovis Milhe Virginie , Viton Jean-Michel , Attarian Sharam , Bensoussan Laurent
Published: February 2024

Facioscapulohumeral muscular dystrophy (FSHD) is a common form of adult muscular dystrophy often resulting also in cardiorespiratory deconditioning and weakness of the lower limbs. Although previous studies examined outcomes of interventions aimed at improving either cardiorespiratory fitness or muscle strength, the potential benefits of a rehabilitation program targeting both remain unexplored. Thus, the aim of this study was to evaluate changes following participation in a rehabilitation program combining aerobic and strength exercises. We conducted a retrospective analysis of 10 subjects with FSHD who participated in our rehabilitation program during 2018 and 2019. Each of the 20 sessions consisted of aerobic training on a cycloergometer and a moderate lower limb strength exercises on an isokinetic machine in combination with conventional therapy. The primary outcomes were walking speed, aerobic performance and isokinetic strength of the knee extensors and flexors. The secondary outcomes were fatigue, insomnia. VO2max and walking speed increased significantly by 2.125 ml·kg−1·min−1 [95% confidence interval (CI): 0.75–3.62, P = 0.022] and 0.28 m/s (95% CI: 0.16–0.4, P = 0.002), respectively. The effect size was small for V02max (Hedge’s g, 0.44; 95% CI: −0.5 to 1.37) and large for walking speed (Hedge’s g, 0.99; 95% CI: 0.06–1.92). The knee flexor strength significantly increased at rehabilitation discharge (repeated measures analysis of variance P = 0.004). Positive changes in fatigue and insomnia were also observed. Our preliminary results provide evidence that a relatively short course of a comprehensive rehabilitation program targeting both cardiorespiratory fitness and knee muscle strength can be beneficial for people with FSHD, which warrants further prospective studies.
Social media influenced self-application of cyanoacrylate for double chin reduction in an adolescent girl: an unusual case of post-inflammatory hyperpigmentation
Authors: Agrawal Saurav , Pant Ved Prakash , Pandey Anup , Acharya Sabin , Sitaula Seema , Rayamajhi Aadesh , Pant Deepak Raj
Published: February 2024

Introduction:

Cyanoacrylate, used as a topical adhesive for wound closure in clinical settings, can result in poor cosmetic outcome on application to skin. Lack of formal medical or dermatological training among social media influencers poses risks of improper diagnosis, incorrect treatments, ineffective home remedies, and potential self-injury or long-term skin effects, especially among adolescents.

Case presentation:

The authors present a case of a young girl with a persistent post-inflammatory hyperpigmentation after using cyanoacrylate on her chin as a home remedy to reduce her double chin problem after learning from a video on social media. Biopsy findings were consistent with post-inflammatory hyperpigmentation in dermis.

Clinical discussion:

Application of cyanoacrylate over skin can result in allergic reactions, burn injuries, infections, itching, skin blistering, and aesthetic issues. Persistent post-inflammatory hyperpigmentation can be a poor cosmetic outcome on application of cyanoacrylate over skin.

Conclusion:

Inadequate social media safety regulations require healthcare professionals to be aware of social trends among adolescents and to encourage them for open conversations and professional help-seeking during times of distress in this digital era.
Competency-Based Education in RN to BSN Programs
Authors: Robinson Jamie , Jagiello Karen P. , McElroy Lori , LoVerde Janet , Jowell Vicki , Good Palmira , Brink Stephanie
Published: February 2024

Background:

The call for nursing education reform has never been louder. National organizations recognize the urgent need to prepare nursing students to practice competently, moving away from traditional teaching and curricula and to competency-based education (CBE) strategies to prepare future nurses for independent clinical practice.

Problem:

The 2021 American Association of Colleges of Nursing Essentials do not account for the competencies achieved in registered nurse (RN) associate degree and diploma programs. This presents a challenge for RN to bachelor of science in nursing (BSN) program administrators and faculty when designing curricula to meet the new Essentials.

Approach:

The Essentials crosswalk created by the National RN-Baccalaureate Faculty Forum serves as a foundational guide for the development of the template models discussed in this article.

Conclusion:

This article provides a template of instructional models for implementing CBE in RN to BSN programs.
Glandular Lesions of the Urinary Bladder: Diagnostic and Molecular Updates
Authors: Reis Henning , Paner Gladell P.
Published: February 2024

Glandular lesions in the urinary tract or their associated pathologies can pose a diagnostic challenge. There is a variety of benign alterations and tumor types that need to be taken into account in differential diagnostic considerations. In recent times, efforts for better defining these alterations or lesions both on the histopathological and molecular levels have been undertaken. This article will provide an update on current diagnostic and molecular considerations of these lesions.
Epidemiology of community-acquired pneumonia caused by Streptococcus pneumoniae in older adults: a narrative review
Authors: Elias Christelle , Nunes Marta C. , Saadatian-Elahi Mitra
Published: February 2024

Purpose of review

This review covers updated perspectives on different aspects of pneumococcal community-acquired pneumonia (pCAP), including the epidemiology, clinical presentation, risk factors, antibiotic treatment, and existing preventive strategies in older adults.

Recent findings

pCAP remains the most prevalent condition among lower respiratory tract infections in the older adults according to Global Burden of Diseases 2019. Older adults can display atypical symptoms such as confusion, general clinical deterioration, new onset of and exacerbation of underlying illness that might trigger clinical suspicion of pCAP. Older adults with pCAP often experience increased disease severity and a higher risk of pulmonary complications compared with younger individuals, owing to age-related changes in immunity and a higher prevalence of comorbidities. Vaccination stands fundamental for prevention, emphasizing the need for effective immunization strategies, specifically tailored for older adults. There is a pressing need to reinforce efforts aimed at boosting pneumococcal vaccination rates.

Despite a high morbidity and mortality, the burden of pCAP, in particular hospital admission and occurrence of invasive infections, among the elderly population is not sufficiently documented. This review findings emphasize the substantial burden of pCAP in this vulnerable population, driven by factors such as advancing age and underlying comorbidities. The emergence of antibiotic-resistant pneumococcal strains further complicates treatment decisions and highlights the importance of tailored approaches for managing pCAP in older adults.
COMPREHENSIVE THERAPEUTIC EFFICACY ANALYSIS OF INTRAVENOUS IMMUNOGLOBULIN IN TREATING SEPSIS-INDUCED COAGULOPATHY: A SINGLE-CENTER, RETROSPECTIVE OBSERVATIONAL STUDY
Authors: Fang Jingyun , Huang Peng , Cui Wanfu , Lin Ye , Rong Dan , Li Xu
Published: February 2024

Objective: The aim of the study is to investigate the efficacy of intravenous immunoglobulin (IVIg) in treating sepsis-induced coagulopathy (SIC). Methods: A retrospective controlled analysis was conducted on 230 patients with SIC at Ganzhou People’s Hospital from January 2016 to December 2022. All patients were screened using propensity score matching and treated according to the SSC2016 guidelines. Compared with the control group (n = 115), patients in the test group (n = 115) received IVIg (200 mg/kg.d) for 3 consecutive days after admission. The rating scales, coagulation function, survival, and treatment duration were evaluated. Results: On day 3 of treatment, both groups exhibited reduced platelet and thromboelastogram (TEG) maximum amplitude (MA) levels, with the control group showing a more significant decrease (P < 0.05). By the fifth day, these levels had recovered in both groups. However, the test group experienced a significant increase by day 7 (P < 0.05). Coagulation factors II and X began to increase on day 3, and normalization was significantly faster in the test group on day 5 (P < 0.05). The levels of prothrombin time, international normalized ratio, activated partial thromboplastin time, d-dimer, fibrinogen, fibrin degradation products, TEG-R, and TEG-K exhibited a notable decline on day 3 and demonstrated significantly faster recovery on day 5 in the test group (P < 0.05). In addition, both groups showed a reduction in Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment, disseminated intravascular coagulation, and lactate (LAC) levels on day 3, but the test group’s scores decreased significantly more by day 7 (P < 0.05). Within the test group, white blood cell count, C-reactive protein, procalcitonin, IL-6, and T
max levels were lower (P < 0.05). Furthermore, the test group demonstrated shorter duration for intensive care unit stay, mechanical ventilation, and continuous renal replacement therapy (P < 0.05). No significant differences were observed in the duration of fever or vasoactive drug use between the groups. However, the log-rank method indicated a higher 28-day survival rate in the test group (P < 0.05). Conclusion: IVIg can successfully increase platelet count and coagulation factors, correct coagulation disorders, enhance organ function, and reduce 28-day mortality in patients with SIC.
Habitat complexity influences neuron number in six species of Puerto Rican
Anolis
Authors: Storks Levi , Garcia Jessica , Perez-Martinez Christian A. , Leal Manuel
Published: February 2024

Elucidating the selective forces shaping the diversity of vertebrate brains continues to be a major area of inquiry, particularly as it relates to cognition. Historically brain evolution was interpreted through the lens of relative brain size; however, recent evidence has challenged this approach. Investigating neuroanatomy at a finer scale, such as neuron number, can provide new insights into the forces shaping brain evolution in the context of information processing capacity. Ecological factors, such as the complexity of a species' habitat, place demands on cognition that could shape neuroanatomy. In this study, we investigate the relationship between neuron number and habitat complexity in three brain regions across six closely related anole species from Puerto Rico. After controlling for brain mass, we found that the number of neurons increased with habitat complexity across species in the telencephalon and ‘rest of the brain,’ but not in the cerebellum. Our results demonstrate that habitat complexity has shaped neuroanatomy in the Puerto Rican anole radiation and provide further evidence of the role of habitat complexity in vertebrate brain evolution.
Predicting potential SARS-CoV-2 mutations of concern via full quantum mechanical modelling
Authors: Zaccaria Marco , Genovese Luigi , Lawhorn Brigitte E. , Dawson William , Joyal Andrew S. , Hu Jingqing , Autissier Patrick , Nakajima Takahito , Johnson Welkin E. , Fofana Ismael , Farzan Michael , Momeni Babak
Published: February 2024

Ab initio
quantum mechanical models can characterize and predict intermolecular binding, but only recently have models including more than a few hundred atoms gained traction. Here, we simulate the electronic structure for approximately 13 000 atoms to predict and characterize binding of SARS-CoV-2 spike variants to the human ACE2 (hACE2) receptor using the quantum mechanics complexity reduction (QM-CR) approach. We compare four spike variants in our analysis: Wuhan, Omicron, and two Omicron-based variants. To assess binding, we mechanistically characterize the energetic contribution of each amino acid involved, and predict the effect of select single amino acid mutations. We validate our computational predictions experimentally by comparing the efficacy of spike variants binding to cells expressing hACE2. At the time we performed our simulations (December 2021), the mutation A484K which our model predicted to be highly beneficial to ACE2 binding had not been identified in epidemiological surveys; only recently (August 2023) has it appeared in variant BA.2.86. We argue that our computational model, QM-CR, can identify mutations critical for intermolecular interactions and inform the engineering of high-specificity interactors.
Combining single-molecule and expansion microscopy in fission yeast to visualize protein structures at the nanostructural level
Authors: Vojnovic Ilijana , Caspari Oliver D. , Hoşkan Mehmet Ali , Endesfelder Ulrike
Published: February 2024

In this work, we have developed an expansion microscopy (ExM) protocol that combines ExM with photoactivated localization microscopy (ExPALM) for yeast cell imaging, and report a robust protocol for single-molecule and expansion microscopy of fission yeast, abbreviated as SExY. Our optimized SExY protocol retains about 50% of the fluorescent protein signal, doubling the amount obtained compared to the original protein retention ExM (proExM) protocol. It allows for a fivefold, highly isotropic expansion of fission yeast cells, which we carefully controlled while optimizing protein yield. We demonstrate the SExY method on several exemplary molecular targets and explicitly introduce low-abundant protein targets (e.g. nuclear proteins such as cbp1 and mis16, and the centromere-specific histone protein cnp1). The SExY protocol optimizations increasing protein yield could be beneficial for many studies, when targeting low abundance proteins, or for studies that rely on genetic labelling for various reasons (e.g. for proteins that cannot be easily targeted by extrinsic staining or in case artefacts introduced by unspecific staining interfere with data quality).
An Eulerian hyperbolic model for heat transfer derived via Hamilton’s principle: analytical and numerical study
Authors: Dhaouadi Firas , Gavrilyuk Sergey
Published: February 2024

In this paper, we present a new model for heat transfer in compressible fluid flows. The model is derived from Hamilton’s principle of stationary action in Eulerian coordinates, in a setting where the entropy conservation is recovered as an Euler–Lagrange equation. A sufficient criterion for the hyperbolicity of the model is formulated. The governing equations are asymptotically consistent with the Euler equations for compressible heat conducting fluids, provided the addition of suitable relaxation terms. A study of the Rankine–Hugoniot conditions and Clausius–Duhem inequality is performed for a specific choice of the equation of state. In particular, this reveals that contact discontinuities cannot exist while expansion waves and compression fans are possible solutions to the governing equations. Evidence of these properties is provided on a set of numerical test cases.
Bioinformatics analysis of the antigenic epitopes of L7/L12 protein in the B- and T-Cells active against  Brucella melitensis

Authors: Zhang Jingjie , Baigued Huricha , Chen Shana , Borigen Haiyan , Tana Tana , Quan Fu , Yang Dezhi
Published: February 2024

Objective: To analyze the physicochemical properties, spatial structure, and protein–protein interactions (PPIs) of L7/L12 protein using bioinformatics methods and predict their B- and T-cell epitopes to lay a theoretical foundation for developing a novel multiepitope vaccine. Methods: The NCBI database was searched for the amino acid sequences of L7/L12 from Brucella melitensis. In addition, the online softwares, ProtParam and ProtScale, were used to predict the physicochemical properties; NetPhos3.1 and CD-search to predict the phosphorylation sites and conserved domains; SOMPA and SWISS-MODEL to predict the secondary and tertiary structures; the STRING database to analyze the PPIs; and the IEDB, ABCpred, SVMTrip, and SYFPEITHI databases to predict the B- and T-cell epitopes.Results: L7/L12, consisting of 124 amino acids, was determined to be a stable, intracellular, hydrophilic protein containing 11 phosphorylation sites and ribosomal protein-related conserved domains. α-helices accounted for 70.16%, β-turns for 2.42%, extended strands for 8.87%, and irregular coils for 18.55% of the secondary structure. The PPIs indicated that L7/L12 was involved in the constitution of ribosomes and regulating the accuracy of the translation process. Three B-cell and six T-cell epitopes were finally screened by comparing multiple databases. Conclusions: L7/L12, which governs the ac translation curate of proteins, possesses several potentially advantageous epitopes, laying a theoretical foundation for designing multiepitope vaccines.
Mesenchymal stem cell-derived extracellular vesicles attenuate symptoms in dextran sodium sulfate-induced ulcerative colitis mouse model
Authors: Zhai Yanhua , Liu Guowu , Cui Chuang , Yi Yuan , Yan Yu , Zhang Lei , Wang Wan , He Xinjun , Xu Ke
Published: February 2024

Inflammatory bowel disease (IBD) refers to a group of multifactorial and chronic inflammation affecting intestinal tract. Based on the pathogenic mechanisms, IBD mainly comprised of two categories: ulcerative colitis (UC) and Crohn’s disease (CD). In this study, we established a dextran sulfate sodium (DSS)-induced colitis model to mimic UC. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) as therapeutic vectors have shown regenerating effect of damaged tissues. Here, intravenous administration of MSC-EVs ameliorated IBD symptoms including gaining weight, reducing disease activity index and restoring colon length. In addition, the protective effect of MSC-EVs were demonstrated by repairing colon mucosa and reducing the infiltration of macrophages in submucosa. Collectively, MSC-EV shows a therapeutic potential for IBD.
The global root exudate carbon flux
Authors: Chari Nikhil R. , Tumber-Dávila Shersingh Joseph , Phillips Richard P. , Bauerle Taryn L. , Brunn Melanie , Hafner Benjamin D. , Klein Tamir , Obersteiner Sophie , Reay Michaela K. , Ullah Sami , Taylor Benton N.
Published: February 2024

Root exudation, the export of low-molecular weight organic carbon (C) from living plant roots to soil, influences microbial activity, nutrient availability, and ecosystem feedbacks to climate change, but the magnitude of this C flux at ecosystem and global scales is largely unknown. Here, we synthesizein situmeasurements of root exudation rates and couple those to estimates of fine root biomass to estimate global and biome-level root exudate C fluxes. We estimate a global root exudate flux of 15.2 PgC y-1, or about 10% of global annual gross primary productivity. We found no differences in root mass-specific exudation rates among biomes, though total exudate fluxes are estimated to be greatest in grasslands owing to their high density of absorptive root biomass. Our synthesis highlights the global importance of root exudates in the terrestrial C cycle and identifies regions where morein situmeasurements are needed to improve future estimates of root exudate C fluxes.
Selective epithelial expression ofKRASG12Dmutation drives ductal pancreatic neoplasia in Oncopigs
Authors: Jara Carlos P , Al-Gahmi Al-Murtadha , Lazenby Audrey , Hollingsworth Michael A. , Carlson Mark A.
Published: February 2024

Background

Pancreatic ductal adenocarcinoma (PDAC) remains a formidable challenge in oncology, characterized by a high mortality rate, largely attributable to delayed diagnosis and the intricacies of its tumor microenvironment. Innovations in modeling pancreatic epithelial transformation provide valuable insights into the pathogenesis and potential therapeutic strategies for PDAC.

Methods

We employed a porcine (Oncopig) model, utilizing the Ad-K8-Cre adenoviral vector, to investigate the effects of variable doses (107to 1010pfu) on pancreatic epithelial cells. This vector, the expression from which being driven by a Keratin-8 promoter, will deliver Cre-recombinase specifically to epithelial cells. Intraductal pancreatic injections in transgenic Oncopigs (LSL-KRASG12D-TP53R167H) were performed with histologically based evaluation at 2 months post-injection.

Results

Specificity of the adenoviral vector was validated through Keratin-8 expression and Cre-recombinase activity. We confirmed that the Ad-K8-Cre adenoviral vector predominantly targets ductal epithelial cells lining both large and small pancreatic ducts, as evidenced by Keratin 8 and CAM5.2 staining. Higher doses resulted in significant tissue morphology changes, including atrophy, and enlarged lymph nodes. Microscopic examination revealed concentration-dependent proliferation of the ductal epithelium, cellular atypia, metaplasia, and stromal alterations. Transgene expression was confirmed with immunohistochemistry. Desmoplastic responses were evident through vimentin, α-SMA, and Masson’s trichrome staining, indicating progressive collagen deposition, particularly at the higher vector doses.

Conclusion

Our study suggests a distinct dose-response relationship of Ad-K8-Cre in inducing pancreatic epithelial proliferation and possible neoplasia in an Oncopig model. All doses of the vector induced epithelial proliferation; the higher doses also produced stromal alterations, metaplasia, and possible neoplastic transformation. These findings highlight the potential for site-specific activation of oncogenes in large animal models of epithelial tumors, with the ability to induce stromal alterations reminiscent of human PDAC.
Cerebra: a computationally efficient framework for accurate protein structure prediction
Authors: Hu Jian , Wang Weizhe , Gong Haipeng
Published: February 2024

Abstract

Remarkable progress has been made in the field of protein structure prediction in the past years. State-of-the-art methods like AlphaFold2 and RoseTTAFold2 achieve prediction accuracy close to experimental structural determination, but at the cost of heavy computational consumption for model training. In this work, we propose a new protein structure prediction framework, Cerebra, for improving the computational efficiency of protein structure prediction. In this innovative network architecture, multiple sets of atomic coordinates are predicted parallelly and their mutual complementary is leveraged to rapidly improve the quality of predicted structures through a novel attention mechanism. Consequently, Cerebra markedly reduces the model training consumption, achieving a training acceleration of at least 7 folds, in comparison to OpenFold, the academic version of AlphaFold2. When evaluated on the CAMEO and CASP15 sets, the Cerebra model insufficiently trained on a single GPU only shows slight performance inferiority to the published OpenFold model.
GraphCompass: Spatial metrics for differential analyses of cell organization across conditions
Authors: Ali Mayar , Kuijs Merel , Hediyeh-zadeh Soroor , Treis Tim , Hrovatin Karin , Palla Giovanni , Schaar Anna C. , Theis Fabian J.
Published: February 2024

Spatial omics technologies are increasingly leveraged to characterize how disease disrupts tissue organization and cellular niches. While multiple methods to analyze spatial variation within a sample have been published, statistical and computational approaches to compare cell spatial organization across samples or conditions are mostly lacking. We present GraphCompass, a comprehensive set of omics-adapted graph analysis methods to quantitatively evaluate and compare the spatial arrangement of cells in samples representing diverse biological conditions. GraphCompass builds upon the Squidpy spatial omics toolbox and encompasses various statistical approaches to perform cross-condition analyses at the level of individual cell types, niches, and samples. Additionally, GraphCompass provides custom visualization functions that enable effective communication of results. We demonstrate how GraphCompass can be used to address key biological questions, such as how cellular organization and tissue architecture differ across various disease states and which spatial patterns correlate with a given pathological condition. GraphCompass can be applied to various popular omics techniques, including, but not limited to, spatial proteomics (e.g. MIBI-TOF), spot-based transcriptomics (e.g. 10x Genomics Visium), and single-cell resolved transcriptomics (e.g. Stereo-seq). In this work, we showcase the capabilities of GraphCompass through its application to three different studies that may also serve as benchmark datasets for further method development. With its easy-to-use implementation, extensive documentation, and comprehensive tutorials, GraphCompass is accessible to biologists with varying levels of computational expertise. By facilitating comparative analyses of cell spatial organization, GraphCompass promises to be a valuable asset in advancing our understanding of tissue function in health and disease.
Indexing Healthcare Access and Quality for Surgically Amenable Causes of Death: A Global Analysis of 204 Countries and Territories from 1990 to 2019
Authors: Zadey Siddhesh , Smith Emily R. , Staton Catherine A. , Fitzgerald Tamara N. , Vissoci Joao Ricardo Nickenig
Published: February 2024

Background

We analyzed the healthcare access and quality (HAQ) index for surgically amenable causes, its progress over time, and the gap compared to non-surgical HAQ across 204 countries and territories from 1990 to 2019 for children (up to 14 years) and overall populations.

Study Design

The Global Burden of Disease 2019 study provided mortality-to-incidence ratios and risk-standardized death rates for 32 causes with preventable mortality. Of these, 14 (18) and 9 (17) causes were considered surgical (non-surgical) for overall population and children, respectively. We constructed composite indices ranging from 0 (worst) to 100 (best) using the adjusted Mazziotta Pareto index methodology. The ratio of surgical HAQ in 2019 to that in 1990 noted change over time. Surgical-to-non-surgical HAQ ratio gave the relative gap in 2019. Ratios >1 depicted improvement over time or better performing surgical care systems.

Results

In 2019, the overall surgical HAQ varied from 18.00 for the Central African Republic to 98.25 for Canada. The child surgical HAQ index varied from 39.87 for Chad to 99.41 for San Marino. For both surgical HAQ indices, 202 countries noted progress from 1990 to 2019. Only 31 countries (15.2%) had greater surgical HAQ index values than their non-surgical counterparts. The child surgical HAQ index lagged behind non-surgical for 61.28% of countries.

Conclusion

Low-income countries had limited progress in surgical HAQ indices since 1990 and lagged behind non-surgical HAQ index in 2019 the most. These findings are valuable for global evaluations, policymaking, and advocacy for investing in surgical care.
Whole Exome and Transcriptome Sequencing of Stage-Matched, Outcome-Differentiated Cutaneous Squamous Cell Carcinoma Identifies Gene Expression Patterns Associated with Metastasis and Poor Outcomes
Authors: Nassir Shams , Yousif Miranda , Li Xing , Severson Kevin , Hughes Alysia , Kechter Jacob , Hwang Angelina , Boudreaux Blake , Bhullar Puneet , Zhang Nan , Butterfield Duke , Ma Tao , Ogbaudu Ewoma , Costello Collin M , Nelson Steven , DiCaudo David J , Sekulic Aleksandar , Baum Christian , Pittelkow Mark , Mangold Aaron R
Published: February 2024

Cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers in humans and kills as many people annually as melanoma. The mutational and transcriptional landscape of cSCC has identified driver mutations associated with disease progression as well as key pathway activation in the progression of pre-cancerous lesions. The understanding of the transcriptional changes with respect to high-risk clinical/histopathological features and outcome is poor. Here, we examine stage-matched, outcome-differentiated cSCC and associated clinicopathologic risk factors using whole exome and transcriptome sequencing on matched samples. Exome analysis identified key driver mutations includingTP53,CDKN2A,NOTCH1,SHC4,MIIP,CNOT1,C17orf66,LPHN22, andTTC16and pathway enrichment of driver mutations in replicative senescence, cellular response to UV, cell-cell adhesion, and cell cycle. Transcriptomic analysis identified pathway enrichment of immune signaling/inflammation, cell-cycle pathways, extracellular matrix function, and chromatin function. Our integrative analysis identified 183 critical genes in carcinogenesis and were used to develop a gene expression panel (GEP) model for cSCC. Three outcome-related gene clusters included those involved in keratinization, cell division, and metabolism. We found 16 genes were predictive of metastasis (Risk score ≥ 9 Met & Risk score < 9 NoMet). The Risk score has an AUC of 97.1% (95% CI: 93.5% - 100%), sensitivity 95.5%, specificity 85.7%, and overall accuracy of 90%. Eleven genes were chosen to generate the risk score for Overall Survival (OS). The Harrell’s C-statistic to predict OS is 80.8%. With each risk score increase, the risk of death increases by 2.47 (HR: 2.47, 95% CI: 1.64-3.74; p<0.001) after adjusting for age, immunosuppressant use, and metastasis status.
Neural basis of perceptual surface qualities: Evidence from EEG decoding
Authors: Orima Taiki , Wakita Suguru , Motoyoshi Isamu
Published: February 2024

The human visual system can easily recognize object material categories and estimate surface properties such as glossiness and smoothness. A number of psychophysical and computational studies suggest that the material perception depends on global feature statistics of the entire image at multiple processing levels. Neural representations of such global features, which is independent of precise retinotopy, may be captured even by EEG that have low spatial resolution. To test this possibility, here we measured visual evoked potentials (VEPs) for 191 natural images consisting of 20 categories of materials. We then sought to classify material categories and surface properties from the VEPs, and to reconstruct the rich phenomenological appearance of materials themselves via neural representations of global features as estimated from the VEPs. As a result, we found that material categories were correctly classified by the VEPs even at latencies of 150 ms or less. The apparent surface properties were also significantly classified within 175 ms (lightness, colorfulness, and smoothness) and after 200 ms (glossiness, hardness, and heaviness). In a subsequent reverse-correlation analysis, we further found that the VEPs at these latencies are highly correlated with low- and high-level global feature statistics of the surface images; Portilla-Simoncelli texture statistics and style information in deep convolutional neural network (dCNN), indicating that neural activities about such global features are reflected in the VEPs that enabled successful classification of materials. To demonstrate this idea more directly, we trained deep generative models (MVAE models) that reconstruct the surface image itself from the VEPs via style information (gram matrix of the dCNN output). The model successfully reconstructed realistic surface images, a part of which were nearly indistinguishable from the original images. These findings suggest that the neural representation of statistical image features, which were formed at short latencies in the visual cortex and reflected even in EEG signals, not simply enable human visual system to recognize material categories and evaluate surface properties but provides the essential basis for rich and complex phenomenological qualities of natural surfaces.
Deep mutational scanning reveals functional constraints and antigenic variability of Lassa virus glycoprotein complex
Authors: Carr Caleb R. , Crawford Katharine H. D. , Murphy Michael , Galloway Jared G. , Haddox Hugh K. , Matsen Frederick A. , Andersen Kristian G. , King Neil P. , Bloom Jesse D.
Published: February 2024

Lassa virus is estimated to cause thousands of human deaths per year, primarily due to spillovers from its natural host,Mastomysrodents. Efforts to create vaccines and antibody therapeutics must account for the evolutionary variability of Lassa virus’s glycoprotein complex (GPC), which mediates viral entry into cells and is the target of neutralizing antibodies. To map the evolutionary space accessible to GPC, we use pseudovirus deep mutational scanning to measure how nearly all GPC amino-acid mutations affect cell entry and antibody neutralization. Our experiments define functional constraints throughout GPC. We quantify how GPC mutations affect neutralization by a panel of monoclonal antibodies and show that all antibodies are escaped by mutations that exist among natural Lassa virus lineages. Overall, our work describes a biosafety-level-2 method to elucidate the mutational space accessible to GPC and shows how prospective characterization of antigenic variation could aid design of therapeutics and vaccines.