bluuebunny/crossref_metadata_2025 huggingface dataset:
lncRNASNP v3: an updated database for functional variants in long non-coding RNAs
Authors: Yang Yanbo , Wang Dongyang , Miao Ya-Ru , Wu Xiaohong , Luo Haohui , Cao Wen , Yang Wenqian , Yang Jianye , Guo An-Yuan , Gong Jing
Published: November 2022

Long non-coding RNAs (lncRNAs) act as versatile regulators of many biological processes and play vital roles in various diseases. lncRNASNP is dedicated to providing a comprehensive repository of single nucleotide polymorphisms (SNPs) and somatic mutations in lncRNAs and their impacts on lncRNA structure and function. Since the last release in 2018, there has been a huge increase in the number of variants and lncRNAs. Thus, we updated the lncRNASNP to version 3 by expanding the species to eight eukaryotic species (human, chimpanzee, pig, mouse, rat, chicken, zebrafish, and fruitfly), updating the data and adding several new features. SNPs in lncRNASNP have increased from 11 181 387 to 67 513 785. The human mutations have increased from 1 174 768 to 2 387 685, including 1 031 639 TCGA mutations and 1 356 046 CosmicNCVs. Compared with the last release, updated and new features in lncRNASNP v3 include (i) SNPs in lncRNAs and their impacts on lncRNAs for eight species, (ii) SNP effects on miRNA−lncRNA interactions for eight species, (iii) lncRNA expression profiles for six species, (iv) disease & GWAS-associated lncRNAs and variants, (v) experimental & predicted lncRNAs and drug target associations and (vi) SNP effects on lncRNA expression (eQTL) across tumor & normal tissues. The lncRNASNP v3 is freely available at http://gong_lab.hzau.edu.cn/lncRNASNP3/.
Experimental Crystallization of the Beauvoir Granite as a Model for the Evolution of Variscan Rare Metal Magmas
Authors: Pichavant Michel
Published: November 2022

New experiments on the strongly peraluminous, Li-, P- and F-rich Beauvoir granite (Massif Central, France) provide a basis for understanding crystallization and chemical fractionation in Variscan rare metal magmas. Crystallization experiments were performed on two natural granite compositions under H2O-saturated conditions at 100, 200, and 300 MPa, from 540°C to 700°C and between ~NNO + 3 and NNO-1.4. Experimental charges were examined by SEM and their products (glasses and crystals) analyzed for major elements by EMPA. Trace element concentrations in selected glasses were determined by LA ICP-MS. Despite experimental durations commonly exceeding 1000 h and some up to 4000 h, kinetic problems were encountered in particular in the 100 MPa charges whereas, at 200 and 300 MPa, results consistent with previous melting experiments were obtained. Beauvoir melts crystallize quartz, plagioclase, K-feldspar and mica as major phases. At NNO-1.4, mica is a biotite, whereas it is a Li-mica between ~NNO+3 and NNO-1. Apatite, Fe-Ti oxides, either hematite or magnetite, topaz, amblygonite, cassiterite and columbite-tantalite appear as accessory phases between ~NNO + 3 and NNO + 1. Experimental plagioclases are albitic (An <4.5 mol%) and more Ca and K-rich than natural albites in the granite whereas experimental K-feldspars are more sodic (Ab <45 mol%) than the natural crystals. The less evolved starting melt crystallized Li phengites whereas the most evolved yielded Li-, F-rich micas near the polylithionite-zinnwaldite series, similar to natural micas in the granite. Equilibrium crystallization increases A/CNK, F and P and concentrates Li, Be, B, Rb, Cs, W, U in the melt. Nb and Ta are also enriched, their behavior being controlled by the solubility of columbite-tantalite in the melt. Other elements are either unchanged (Mn, Zn, Ti) or depleted (Sr, Pb) during magmatic fractionation. Sn is concentrated in Li-mica and hematite, and it behaves compatibly at high fO2. Beauvoir melts crystallize at very low temperatures, below 670°C for the two compositions studied and solidus temperatures, determined from previous melting experiments and confirmed by the new crystallization experiments, are near 550°C. The experiments demonstrate that most of the mineralogical and geochemical characteristics that make the Beauvoir granite distinctive result from magmatic rather than hydrothermal post-magmatic processes. Albitic plagioclase, Li-mica, topaz, and amblygonite are of magmatic origin. Glass major element compositions suggest that the two granite samples represent crystallized liquids. Trace element fractionations for most elements at Beauvoir can be accounted for by magmatic crystallization–differentiation processes. Implications for the mineralogy, fO2, volatile concentrations, crystallization and conditions of emplacement, fractionation mechanisms and origin of the Beauvoir granite are discussed.
Vision transformer assisting rheumatologists in screening for capillaroscopy changes in systemic sclerosis: an artificial intelligence model
Authors: Garaiman Alexandru , Nooralahzadeh Farhad , Mihai Carina , Gonzalez Nicolas Perez , Gkikopoulos Nikitas , Becker Mike Oliver , Distler Oliver , Krauthammer Michael , Maurer Britta
Published: November 2022

Objectives

The first objective of this study was to implement and assess the performance and reliability of a vision transformer (ViT)-based deep-learning model, an ‘off-the-shelf’ artificial intelligence solution, for identifying distinct signs of microangiopathy in nailfold capilloroscopy (NFC) images of patients with SSc. The second objective was to compare the ViT’s analysis performance with that of practising rheumatologists.

Methods

NFC images of patients prospectively enrolled in our European Scleroderma Trials and Research group (EUSTAR) and Very Early Diagnosis of Systemic Sclerosis (VEDOSS) local registries were used. The primary outcome investigated was the ViT’s classification performance for identifying disease-associated changes (enlarged capillaries, giant capillaries, capillary loss, microhaemorrhages) and the presence of the scleroderma pattern in these images using a cross-fold validation setting. The secondary outcome involved a comparison of the ViT’s performance vs that of rheumatologists on a reliability set, consisting of a subset of 464 NFC images with majority vote–derived ground-truth labels.

Results

We analysed 17 126 NFC images derived from 234 EUSTAR and 55 VEDOSS patients. The ViT had good performance in identifying the various microangiopathic changes in capillaries by NFC [area under the curve (AUC) from 81.8% to 84.5%]. In the reliability set, the rheumatologists reached a higher average accuracy, as well as a better trade-off between sensitivity and specificity compared with the ViT. However, the annotators’ performance was variable, and one out of four rheumatologists showed equal or lower classification measures compared with the ViT.

Conclusions

The ViT is a modern, well-performing and readily available tool for assessing patterns of microangiopathy on NFC images, and it may assist rheumatologists in generating consistent and high-quality NFC reports; however, the final diagnosis of a scleroderma pattern in any individual case needs the judgement of an experienced observer.
Prevalence and clinical course of patients with chronic heart failure secondary to chronic Chagas heart disease associated with obstructive coronary artery disease
Authors: Otaviano Ana Paula , Cardinalli-Neto Augusto , Nakazone Marcelo A , Nogueira Paulo R , Bestetti Reinaldo B
Published: November 2022

Background

The prevalence and the outcomes of patients with chronic Chagas heart disease with obstructive coronary artery disease (CCHD-CAD) and chronic heart failure (CHF) with precordial chest pain are unsettled. Accordingly, the aim of this study was to determine the prevalence and clinical course of patients with CHF secondary to CCHD-CAD.

Methods

Patients with positive serology for Chagas disease and systolic CHF were included; those with precordial chest pain and at least two risk factors for CAD underwent coronary arteriogram.

Results

In total 262 patients were included in the investigation; 234 (89%) had CHF secondary to CCHD alone, and 28 (11%) with CHF secondary to CCHD-CAD, as observed at coronary arteriogram. The survival probability of patients with CHF secondary to CCHD alone at 12, 24, 36, 48 and 72 mo was 79%, 64%, 54%, 44% and 33%, respectively, whereas survival probability for patients with CHF secondary to CCHD-CAD at 12, 24, 36, 48 and 72 mo was 96%, 80%, 71%, 66% and 57%, respectively (p=0.04).

Conclusions

In patients with CCHD with CHF, the prevalence of CAD of 11% is not neglectable in those with precordial chest pain. The outcome for patients with precordial chest pain with CHF secondary to CCHD-CAD is better than that observed in patients with CHF secondary to CCHD alone.
Unsteady aerodynamic performance of a maglev train: the effect of the ground condition
Authors: Meng Shi , Chen Guang , Zhou Dan , Meng Shuang
Published: November 2022

The effect of ground condition on unsteady aerodynamic performance of a maglev train was numerically investigated with an IDDES (Improved Delayed Detached Eddy Simulation) method. The accuracy of the numerical method has been validated by wind tunnel experiments. The flow structure, slipstream and aerodynamic force around the train under stationary and moving ground conditions were compared. Track and ground play a leading role in the influence of wake vortex structure; the flow structure around the train is more complex under the stationary ground boundary condition. Near the nose point of the head and tail vehicles, the peak value of the slipstream under the condition of moving ground is slightly higher than that under stationary ground. In the wake area, the effect of the main vortex structure on both sides of the tail vehicle and the track makes the vortex structure in the wake area stronger than that under moving ground, the slipstream peak is larger and the locus thereof is further forward. In the horizontal direction, the vortex desorption energy near the nose tip of the train is higher on stationary ground, while the vortex desorption energy far from the nose tip of the train is higher on moving ground. Compared with the static ground boundary condition, the resistance coefficient of the head and tail of a maglev train increases by 3.45% and 3.31% respectively under the moving ground boundary condition. The lift coefficient decreases by 157.78% and 5.13%, respectively.
Before-After Study of a Checklist to Improve Acute Care to ICU Handoffs
Authors: Hicks Katherine G. , Downey Lois , Elketami Addy , Nielsen Elizabeth L. , Engelberg Ruth A. , Jennerich Ann L.
Published: November 2022

Transferring care of a patient is a critical process. The objective of this study was to evaluate a checklist to standardize handoffs from acute care to the intensive care unit (ICU). This was a single-center, before-after study of a checklist to standardize transfers of patients from acute care to the medical-cardiac ICU. Clinicians completed surveys about handoffs before and after checklist implementation. The association between study period and survey data was analyzed using multivariable logistic regression with cross-classified multilevel models. Surveys were completed by 179 clinicians. After checklist implementation, handoffs were more likely to occur in the ICU (OR 17.23; 95% CI, 1.81-164.19) and cover patient treatment preferences (OR 2.73; 95% CI, 1.12-6.66). However, checklist uptake was suboptimal (30% of responses indicated checklist use). Implementation of a checklist during acute care to ICU transfers is challenging. Signals suggesting process improvement warrant additional study.
Pelvic Compression Device (Binder) Application Training in Medical Students: A Manikin Study
Authors: Beşer Zafer , Oğuz Ahmet Burak , Koca Ayça , Genç Sinan , Erdurmuş Ömer Yusuf , Polat Onur
Published: November 2022

Background:

Correct application of external pelvic compression devices (binders) is crucial in managing multitrauma patients with suspected pelvic fractures to control hemorrhage. Yet, there is a lack of practical training standards for pelvic compression device application in medical school education.

Objective:

This study aimed to evaluate simulation training of pelvic compression device application by medical students to determine the number of applications required to meet proficiency measured by correct application and timeliness.

Methods:

This is an observational cross-sectional measurement study of a convenience sample of 132 volunteer senior medical students who participated in a 30-min theoretical and simulation training session on the application of pelvic compression devices. The study was conducted between January 1, 2020, and March 1, 2020. Two weeks after the training, the students performed 10 consecutive pelvic compression device applications, each followed by a 5-min feedback session break. Application step accuracy and timing were observed and recorded. The percentage of correct applications was compared by χ2 test.

Results:

The correct application rate for the first application was 42.4%, with an average of 92 s, 95% confidence interval (CI): 91.00–93.72. The highest correct application rate occurred in the eighth application (97%, p < .001), with an average application time of 87 s, 95% CI: 85.62–87.72.

Conclusion:

We found that at least eight pelvic compression device manikin applications were required to achieve proficiency.
Bison Goring Resulting in Abdominal Evisceration and Cervical Fracture: A Case Report
Authors: Miles Gayla , Quinlan Ann , Daniel Craig
Published: November 2022

Background:

Handling livestock can be dangerous, and livestock-related injuries are increasing.

Case Presentation:

An 83-year-old man who was gored and thrown by a bison bull during feeding is presented. The traumatic event resulted in two major injuries: an abdominal laceration with intestinal evisceration and cervical fractures after being lifted and forcefully thrown. The patient's hospital course included emergent surgery using the damage control approach resulting in an open abdomen, postoperatively, intensive care unit placement, and physiological management of the lethal diamond (acidosis, coagulopathy, hypothermia, and hypocalcemia). Finally, the patient's injuries required repeated abdominoplasties, colostomy, and surgical cervical stabilization. Despite a complicated hospitalization, the patient returned to his previous lifestyle within 2 months.

Conclusion:

The geriatric population, despite multiple comorbidities, is active, and their dynamic lifestyle can result in severe injuries. Positive outcomes for this population are possible. Even if severely injured, the geriatric population has the propensity to rebound and survive with early aggressive management.
Perineal Injury via Personal Watercraft Hydrostatic Jet: A Case Report
Authors: Pearson Thomas E. , Elwell Sean , Paidas Charles , Duffy Brian
Published: November 2022

Background:

Traumatic injuries resulting from personal watercraft hydrostatic jets are expected to increase as personal watercrafts are affordable, portable, and used in an increasingly wide range of locales.

Case Presentation:

This case study presents an unusual severe perineal injury in a 17-year-old adolescent girl resulting from a fall from a personal watercraft and contact with the vehicle's hydrostatic jet. This case report provides an overview of the mechanism, treatment, and prevention of personal watercraft injuries.

Conclusion:

Knowledge of this mechanism's potential for serious morbidity and mortality, patient assessment and management principles, and injury prevention strategies are essential to providing effective trauma center care.
Intratympanic Substance Distribution After Injection of Liquid and Thermosensitive Drug Carriers: An Endoscopic Study
Authors: Nieratschker Michael , Yildiz Erdem , Schnoell Julia , Hirtler Lena , Schlingensiepen Reimar , Honeder Clemens , Arnoldner Christoph
Published: November 2022

Objective

In the treatment of inner ear conditions, intratympanic injection emerges as an important drug delivery method. Novel compounds designed for intratympanic injection are routinely loaded in viscous drug carriers. To date, it is unclear if they can freely distribute in the middle ear. The aims of this study were to investigate the middle ear distribution of different drug carriers during intratympanic injection and to determine an optimal injection method for thermosensitive hydrogels.

Methods

Twenty-one human temporal bones were intratympanically injected with fluid drug carriers or poloxamer-407 hydrogels at different tympanic membrane injection sites (inferior, anterior-superior) using different needle types (Whitacre, Quincke). Fluid distribution was evaluated via an endoscopic view. Injection volume, duration, backflow, and overall safety were analyzed.

Results

Liquid drug carriers distribute effortlessly in the middle ear, whereas an additional ventilation hole is advantageous when applying thermosensitive hydrogels. The round window is coated with required volumes between 150 and 200 μl, irrespective of the injection position. Required volumes to also coat the stapedial footplate ranged from 310 to 440 μl. Use of the Whitacre-type needle reduced backflow to the ear canal and enabled longer tympanic membrane visibility when no additional ventilation hole was placed.

Conclusion

Intratympanic injection is a safe and reliable method for the application of thermosensitive hydrogels. The round window niche is readily filled regardless of the injected formulation and injection position. Although fluid drug carriers distribute effortlessly in the middle ear, the placement of an additional ventilation hole might facilitate the application of viscous hydrogels.
One Click Is Not Enough: Anatomy-Based Fitting in Experienced Cochlear Implant Users
Authors: Kurz Anja , Müller-Graff Franz-Tassilo , Hagen Rudolf , Rak Kristen
Published: November 2022

Objective

To evaluate a new methodological approach of applying anatomy-based fitting (ABF) in experienced cochlear implant (CI) users.

Participants

Three experienced unilateral and bilateral CI users with postlingual hearing loss.

Intervention

Postoperative imaging, via a high-volume Dyna computed tomography, and exact electrode measurement positions were integrated into the clinical fitting software following a new procedure, which adapted individual frequency bandwidths within the audio processor.

Main Outcome Measures

Speech perception in quiet and noise, clinical mapping, and self-perceived level of auditory benefit were assessed.

Results

For each CI user, ABF mapping provided better speech perception in quiet and in noise compared with the original clinical fitting mapping. In addition, ABF mapping was accepted in CI users despite unequal bilateral array insertion depths and lengths; however, acceptance was only established if the point of first electrode contact was less than 230 Hz.

Conclusions

ABF mapping increased the acceptance in CI users with longer electrode arrays and in bilateral CI users who were unsatisfied with their device experience. A larger prospective, randomized investigation is currently underway to assess longitudinal outcomes with ABF mapping.
Does Hypochlorous Acid Cause Ototoxicity? An Experimental Study
Authors: Mutlu Ahmet , Gunduz Ayşe Yasemin , Bakici Balci Burcu , Erinc Murat , Bulut Erdogan , Ersoy Onur , Kalcioglu Mahmut Tayyar
Published: November 2022

Aim

Hypochlorous acid (HOCl) is a weak acid that ionizes in water. It is an effective antiseptic exhibiting low toxicity on living tissues. We aimed to investigate the ototoxic effects of HOCl on an animal model by using electrophysiological and histological methods.

Materials and Methods

The study comprised 32 Sprague-Dawley rats, which were separated into four groups: control group (A), saline solution group (B), 70% isopropyl alcohol + 2% chlorhexidine group (C), and HOCl group (D). After recording the auditory brainstem response (ABR) for basal hearing thresholds (8, 16, 24, and 32 kHz), 0.03 ml of the aforementioned materials was injected intratympanically three times every 2 days in groups B, C, and D. ABR measurements were repeated on the 7th and 21st days. All animals were sacrificed, and temporal bones were prepared for examinations of cochlear histology and vascular endothelial growth factor immunohistochemistry.

Results

Basal hearing levels were normal across all frequencies and groups, with no statistical differentiation. On the 7th and 21st days after the ABR test, all other groups demonstrated a significant deterioration in hearing levels compared with group A. When the results from 7th and 21st days were compared within group D, a partial recovery was observed. In histopathology, groups C and D demonstrated moderate and severe cochlear degeneration, along with decreased immunoreactivity in the organ of Corti, stria vascularis, and spiral ligament.

Conclusion

This is the first study to evaluate the safety of using HOCl in otology. Although HOCI is less ototoxic than the disinfectant used, it may have a toxic effect on cochlea.

Level of Evidence: Animal Research.
Racial Disparities in Tympanoplasty Surgery: A 30-Day Morbidity and Mortality National Cohort Study
Authors: Singh Priyanka , Debbaneh Peter , Rivero Alexander
Published: November 2022

Objectives

To assess the impact of race and ethnicity on 30-day complications after tympanoplasty surgery.

Methods

The National Surgical Quality Improvement Program database was queried for tympanoplasty procedures from 2005 to 2019. Demographic, comorbidity, and postoperative complication data were compared according to race using univariate and binary logistic regression analyses.

Results

A total of 11,701 patients were included, consisting of 80.3% White, 3.0% Black, 7.7% Asian, 5.7% Hispanic, 2.5% American Indian/Alaska Native, and 0.8% other. Binary logistic regression model indicated that Black patients had increased odds of unplanned readmittance (p = 0.033; odds ratio [OR], 3.110) and deep surgical site infections (p = 0.008; OR, 6.292). American Indian/Alaska Native patients had increased odds of reoperation (p = 0.022; OR, 6.343), superficial surgical site infections (p < 0.001; OR, 5.503), urinary tract infections (p < 0.001; OR, 18.559), surgical complications (p < 0.001; OR, 3.820), medical complications (p = 0.001; OR, 10.126), and overall complications (p < 0.001; OR, 4.545).

Conclusion

Although Black and American Indian/Alaskan Native patients were more likely to have complications after tympanoplasty surgery after adjusting for comorbidities, age, and sex, these results are tempered by an overall low rate of complications. Future studies should be devoted to understanding the drivers of these health inequities in access to otologic care and surgical treatment to improve outcomes and achieve equitable care.
Metastatic castrate-resistant prostate cancer: a new horizon beyond the androgen receptors
Authors: Roy Soumyajit , Saad Fred
Published: November 2022

Purpose of review

Systemic chemotherapy and second-generation androgen receptor-axis targeted therapies have been in the forefront of management for metastatic castrate-resistant prostate cancer (mCRPC) patients with low or high symptom burden. However, in the recent past, due to improvement in molecular characterization, management of mCRPC has witnessed long strides of advancement. We aim to review the novel nonhormonal and nonchemotherapeutic treatment options.

Recent findings

Poly (ADP-ribose) polymerase inhibitors (PARPis) such as olaparib and rucaparib have been recently approved by the US FDA for use in mCRPC with germline or somatic mutations in homologous recombination repair. The combination of PARPi with androgen receptor axis-targeted agents (ARAT) or dual ARAT-based therapy has shown superior radiographic progression-free survival as a first-line treatment. A combination of AKT inhibitor ipatasertib and abiraterone has shown improvement in radiographic progression-free survival as a first-line treatment. Prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical like 177Lu-PSMA-617, a beta particle emitter has demonstrated improvement in overall survival in mCRPC patients pretreated with ARAT or taxanes. Although immune checkpoint inhibitors are being tested in mCRPC, there is no robust evidence to support this premise.

These new agents have widened the treatment options for mCRPC patients. Overall treatment should be focused on improving survival while limiting the deterrent effect on the quality of life.
Cardiometabolic side effects of androgen deprivation therapy in prostate cancer
Authors: Lafontaine Marie-Lyssa , Kokorovic Andrea
Published: November 2022

Purpose of review

Androgen-deprivation therapy (ADT) is widely employed for treatment of advanced prostate cancer and it is considered the frontline therapy. However, the numerous adverse reactions associated with this treatment option are concerning and its potential association with cardiovascular diseases (CVD) should not be overlooked. In this review, we examine the literature on the cardiovascular side effects of ADT and the physiologic mechanisms underpinning the association with CVD. We will also specifically discuss the different findings regarding the interesting potential disparity in major cardiovascular events among GnRH agonist-treated patients compared with patients undergoing GnRH antagonist treatment.

Recent findings

Androgen-deprivation therapy increases the risk of developing CVD by altering the body composition, metabolism, vascular system, and cardiac physiology. GnRH agonists may pose a higher risk of cardiovascular mortality and morbidity than GnRH antagonists; however, this link remains to be determined. Furthermore, screening for cardiovascular risk factors before and during ADT treatment is a crucial step in preventing major adverse cardiac events in prostate cancer patients. Notably, preexisting CVD and comorbidities have been identified as major key elements predicting cardiovascular events. Early implementation of pharmacological and nonpharmacological treatment strategies is strongly suggested, and regular follow-up visits should be scheduled to continuously assess patients’ cardiovascular risk under ADT.

ADT is a very powerful treatment option for advanced prostate cancer that improves survival outcomes but has the potential of considerably impacting patients’ cardiovascular health. Medical optimization and close monitoring are crucial during treatment with ADT.
Artificial light at night may decrease predation risk for terrestrial insects
Authors: Eckhartt Gregory M. , Ruxton Graeme D.
Published: November 2022

Artificial light at night (ALAN) is thought to be detrimental for terrestrial insect populations. While there exists evidence for lower abundance under ALAN, underlying mechanisms remain unclear. One mechanism by which ALAN may contribute to insect declines may be through facilitating increased predation. We investigated this by experimentally manipulating insect-substitute abundance under differential levels of light. We used insect-containing birdfeed placed at varying distances from streetlights as a proxy for terrestrial insects, inspecting the rate of predation before and after dusk (when streetlights are, respectively, off and on). We found that there was a significantly greater effect of increasing distance on predation after dusk, suggesting that predation was actually reduced by greater levels of artificial light. This may occur because ALAN also increases the vulnerability of insectivores to their own predators. Implications for foraging behaviour and alternative explanations are discussed.
A machine learning approach for the discrimination of theropod and ornithischian dinosaur tracks
Authors: Lallensack Jens N. , Romilio Anthony , Falkingham Peter L.
Published: November 2022

Fossil tracks are important palaeobiological data sources. The quantitative analysis of their shape, however, has been hampered by their high variability and lack of discrete margins and landmarks. We here present the first approach using deep convolutional neural networks (DCNNs) to study fossil tracks, overcoming the limitations of previous statistical approaches. We employ a DCNN to discriminate between theropod and ornithischian dinosaur tracks based on a total of 1372 outline silhouettes. The DCNN consistently outperformed human experts on an independent test set. We also used the DCNN to classify tracks of a large tridactyl trackmaker from Lark Quarry, Australia, the identity of which has been subject to intense debate. The presented approach can only be considered a first step towards the wider application of machine learning in fossil track research, which is not limited to classification problems. Current limitations, such as the subjectivity and information loss inherent in interpretive outlines, may be overcome in the future by training neural networks on three-dimensional models directly, though this will require an increased uptake in digitization among workers in the field.
A game theoretical model for the stimulation of public cooperation in environmental collaborative governance
Authors: Fang Yinhai , Perc Matjaž , Zhang Hui
Published: November 2022

Digital technologies provide a convenient way for the public to participate in environmental governance. Therefore, by means of a two-stage evolutionary model, a new mechanism for promoting public cooperation is proposed to accomplish environmental collaborative governance. Interactive effects of government–enterprise environmental governance are firstly explored, which is the external atmosphere for public behaviour. Second, the evolutionary dynamics of public behaviour is analysed to reveal the internal mechanism of the emergence of public cooperation in environmental collaborative governance projects. Simulations reveal that the interaction of resource elements between government and enterprise is an important basis for environmental governance performance, and that governments can improve this as well as public cooperation by increasing the marginal governance propensity. Similarly, an increase in the government's fixed expenditure item of environmental governance can also significantly improve government–enterprise performance and public cooperation. And finally, the effect of government's marginal incentive propensity on public environmental governance is moderated by enterprises' marginal environmental governance propensity, so that simply increasing the government's marginal incentive propensity cannot improve the evolutionary stable state of public behaviour under the scenario where enterprises’ marginal environmental governance propensity is low.
Nocardia sputi sp. nov. isolated from the sputum of patients with pulmonary infection
Authors: Wang Xiaoxia , Wei Ming , Pu Ji , Huang Yuyuan , Zhang Sihui , Zhou Juan , Wang Licheng , Yang Jing , Li Zhenjun , Zhu Xiong
Published: November 2022

Two Gram-stain-positive, aerobic and rod-shaped actinomycetes (strains CY18T and CY8) were isolated from the sputum of two patients with pulmonary infections, and their taxonomic status was investigated. The 16S rRNA gene sequences and the results of phylogenetic analyses indicated that CY18T and CY8 were identical (100 %) and were most closely related to

Nocardia beijingensis

CGMCC 4.1521T (99.9 %) and

Nocardia araoensis

NBRC 100135T (99.5 %). The predominant cellular fatty acids of CY18T and CY8 were C16 : 0, C18 : 0, C18 : 1ω9c and summed feature 3 (comprising C16 : 1ɷ7c and/or C16 : 1ɷ6c), and the major menaquinone was MK-8(H4ω-cycl).The diagnostic diamino acid in the cell-wall peptidoglycan was meso-diaminopimelic acid. The whole-cell hydrolytic sugar pattern consisted of arabinose and glucose. The polar lipid profile contained diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannoside, two unidentified phospholipids, three unidentified glycolipids and two unidentified lipids.The DNA G+C contents of CY18T and CY8 were 67.9 and 68.0 % respectively. The digital DNA–DNA hybridization and average nucleotide identity values between the two novel strains and closely related species were well under the 70 % and 95–96 % thresholds, respectively, but these values between the two novel strains were 95.5 % and 99.5 %, respectively. On the basis of morphological and chemotaxonomic characteristics and the results of phylogenetic analyses, strains CY18T and CY8 represent a novel species of the genus

Nocardia

, for which the name Nocardia sputi sp. nov. is proposed. The type strain is CY18T (=GDMCC 1.3318T = JCM 33932T).
Association Between Polygenic Risk Score And Gut Microbiome Of Multiple Sclerosis
Authors: Elsayed Noha S. , Valenzuela Robert K. , Kitchner Terrie , Le Thao , Mayer John , Tang Zheng-Zheng , Bayanagari Vishnu R. , Lu Qiongshi , Aston Paula , Anantharaman Karthik , Shukla Sanjay K.
Published: November 2022

Background

Multiple sclerosis (MS) is a complex autoimmune disease in which both the roles of genetic susceptibility and environmental/microbial factors have been investigated. More than 200 genetic susceptibility variants have been identified along with the dysbiosis of gut microbiota, both independently have been shown to be associated with MS. We hypothesize that MS patients harboring genetic susceptibility variants along with gut microbiome dysbiosis are at a greater risk of exhibiting the disease. We investigated the polygenic risk score for MS in conjunction with gut microbiota in the same cohort of 117 relapsing remitting MS (RRMS) and 26 healthy controls. DNA samples were genotyped using Illumina’s Infinium Immuno array-24 v2 chip followed by calculating polygenic risk score and the microbiota was determined by sequencing the V4 hypervariable region of the 16S rRNA gene.

Results

We identified two clusters of MS patients, Cluster A and B both having a higher polygenic risk score than the control group. The Cluster B with the higher polygenic risk score had a distinct gut microbiota, different than the Cluster A. MS group whose microbiome was similar to that of the control group despite a higher genetic risk score than the control group. This could be due to i) the non-active state of the disease in that group of MS patients at the time of fecal sample collection and/or ii) the restoration of the gut microbiome post disease modifying therapy to treat the MS.

Conclusion

Our study showed that there seems to be association between polygenic risk score and gut microbiome dysbiosis in triggering the disease in a small cohort of MS patients. The MS Cluster A who have a higher polygenic risk score but microbiome profile similar to that of healthy controls could be due to the remitting phase of the disease or due to the effect of disease modifying therapies.
High-resolution temporal profiling of the gut microbiome through the whole life of mice
Authors: Takayasu Lena , Watanabe Eiichiro , Umeyama Taichi , Kurokawa Rina , Maskawa Rie , Basu Sumanta , Ogata Yusuke , Kiguchi Yuya , Masuoka Hiroaki , Umezaki Masahiro , Takayasu Hideki , Takayasu Misako , Hattori Masahira , Suda Wataru
Published: November 2022

The temporal changes of the gut microbiome are thought to be critical for understanding its interactions with host aging, but lifelong dynamics within the same individual remain largely unknown. Here we firstly report the high temporal resolution dynamics of gut microbiomes in mice sharing the same genetic background and environment from their birth to natural death, spanning >1,000 days. The 16S rRNA sequencing analysis revealed 9 patterns of OTU temporal dynamics and 38 common “life-core” bacterial species/operational taxonomic units (OTUs) in ≥80% of all samples across the lifespan of individual mice. The life-core OTUs are largely represented by the phylum Bacteroidota, whereas the transient bacterial group predominantly includes the phylum Firmicutes (Bacillota). Despite the shared genetic background and dietary habits, the gut microbiome structure significantly diversified with age and among individuals. A positive correlation existed between longevity and the microbiome α-diversity in middle age (200–500 days) followed by a negative correlation in old age (>700 days), likely influenced by the increase in diversity during the last days of life. The abundance of several “life-core” species also exhibited non-static correlation trends with lifespan. Overall, this research characterized the gut microbiomes based on its persistence over host’s lifetime and suggested a non-static host-microbiome relationship within individual mice.
High-throughput enzymology reveals mutations throughout a phosphatase that decouple catalysis and transition state analog affinity
Authors: Markin C.J. , Mokhtari D.A. , Du S. , Doukov T. , Sunden F. , Fordyce P.M. , Herschlag D.
Published: November 2022

Using High-Throughput Microfluidic Enzyme Kinetics (HT-MEK), we measured over 9,000 inhibition curves detailing impacts of 1,004 single-site mutations throughout the Alkaline Phosphatase PafA on binding affinity for two transition state analogs (TSAs), vanadate and tungstate. As predicted by catalytic models invoking transition state complementary, mutations to active site and active site-contacting residues had highly similar impacts on catalysis and TSA binding. Unexpectedly, most mutations to more distal residues which reduced catalysis had little or no impact on TSA binding and many even increased affinity for tungstate. These disparate effects are accounted for by a model in which distal mutations alter the enzyme’s conformational landscape and increase occupancy of microstates that are catalytically less effective but better able to accommodate larger transition state analogs. In support of this model, glycine substitutions (rather than valine) were more likely to increase tungstate affinity, presumably due to increased conformational flexibility and increased occupancy of previously disfavored microstates. These results indicate that residues throughout an enzyme provide specificity for the transition state and discriminate against analogs that are larger only by tenths of an Ångström. Thus, engineering enzymes that rival the most powerful natural enzymes will likely require consideration not just of residues in and around the active site, but also of more distal residues that shape the enzyme’s conformational landscape and finetune the active site. In addition, the extensive functional communication between the active site and remote residues may provide interconnections needed for allostery and make allostery a highly evolvable trait.

Significance Statement

Transition state analogs (TSAs) resemble fleeting high-energy transition states and have been used to inhibit enzymes in nature and medicine, to learn about enzyme active site features, and to design and select new enzymes. While TSAs mimic transition states, they differ from actual TSs, and we exploit these differences here. Systematic TSA affinity measurements for 1,004 mutants of PafA (a model phosphatase enzyme) revealed effects in and around the active site that mirror their effects on catalysis, but TSA-binding and catalytic effects diverge more distally. These observations suggest that residues throughout an enzyme adjust its conformational landscape on the tenth-Ångström scale to optimize the active site for catalysis, rendering allostery more evolvable in nature but likely complicating enzyme design.
Single Pixel Reconstruction Imaging: taking confocal imaging to the extreme
Authors: Streckaitė Simona , Frolov Dmitrij , Chmeliov Jevgenij , Gelzinis Andrius , Ilioaia Cristian , Rimsky Sylvie , van Grondelle Rienk , Valkunas Leonas , Gall Andrew , Robert Bruno
Published: November 2022

Light nanoscopy is attracting widespread interest for the visualization of fluorescent structures at the nanometer scale, especially in cellular biology. To achieve nanoscale resolution, one has to surpass the diffraction limit—a fundamental phenomenon determining the spot size of focused light. Recently, a variety of methods have overcome this limit, yet in practice they are often constrained by the requirement of special fluorophores, nontrivial data processing, or high price and complex implementation. For this reason, confocal fluorescence microscopy that yields relatively low resolution is still the dominant method in biomedical sciences. It was shown that image scanning microscopy (ISM) with an array detector instead of a point detector could improve the resolution of confocal microscopy. Here we review the principles of the confocal microscopy and present a simple method based on ISM with a different image reconstruction approach, which can be easily implemented in any camera-based laser-scanning set-up to experimentally obtain the theoretical resolution limit of the confocal microscopy. Our method, Single Pixel Reconstruction Imaging (SPiRI) enables high-resolution 3D imaging utilizing image formation only from a single pixel of each of the recorded frames. We achieve experimental axial resolution of 330 nm, which was not shown before by basic confocal or ISM-based systems. Contrary to the majority of techniques, SPiRI method exhibits a low lateral-to-axial FWHM aspect ratio, which means a considerable improvement in 3D fluorescence imaging of cellular structures. As a demonstration of SPiRI application in biomedical sciences, we present a 3D structure of bacterial chromosome with excellent precision.
Microtubule binding-induced allostery promotes LIS1 dissociation from dynein prior to cargo transport
Authors: Ton William D. , Wang Yue , Chai Pengxin , Beauchamp-Perez Cissloyny , Flint Nicholas T. , Lammers Lindsay G. , Xiong Hao , Zhang Kai , Markus Steven M.
Published: November 2022

The lissencephaly-related protein LIS1 is a critical regulator of cytoplasmic dynein that governs motor function and intracellular localization (e.g., to microtubule plus-ends). Although LIS1 binding is required for dynein activity, its unbinding prior to initiation of cargo transport is equally important, since preventing dissociation leads to dynein dysfunction. To understand whether and how dynein-LIS1 binding is modulated, we engineered dynein mutants locked in a microtubule-bound (MT-B) or -unbound (MT-U) state. Whereas the MT-B mutant exhibits low LIS1 affinity, the MT-U mutant binds LIS1 with high affinity, and as a consequence remains almost irreversibly bound to microtubule plus-ends. We find that a monomeric motor domain is sufficient to exhibit these opposing LIS1 affinities, and that this is an evolutionarily conserved phenomenon. Three cryo-EM structures of dynein with and without LIS1 reveal microtubule-binding induced conformational changes responsible for this regulation. Our work reveals key biochemical and structural insight into LIS1-mediated dynein activation.
Molecular diversity and connectivity of accessory olfactory system neurons
Authors: Prakash Nandkishore , Matos Heidi Y , Sebaoui Sonia , Tsai Luke , Tran Tuyen , Aromolaran Adejimi , Atrachji Isabella , Campbell Nya , Goodrich Meredith , Hernandez-Pineda David , Herrero Maria , Hirata Tsutomu , Lischinsky Julieta , Martinez Wendolin , Torii Shisui , Yamashita Satoshi , Sokolowski Katie , Esumi Shigeyuki , Kawasawa Yuka Imamura , Hashimoto-Torii Kazue , Jones Kevin S , Corbin Joshua G
Published: November 2022

Olfaction is the primary sensory modality by which most vertebrate species interpret environmental cues for appropriate behavioral outputs. The olfactory system is subdivided into main (MOS) and accessory (AOS) components which process volatile and non-volatile cues. While much is known regarding the molecular diversity of neurons that comprise the MOS, less is known about the AOS. Here, focusing on the AOS which is largely comprised of the peripheral vomeronasal organ (VNO), the accessory olfactory bulb (AOB) and the medial subnucleus of the amygdala (MeA), we studied the molecular diversity and neuronal subtype connectivity of this interconnected circuit. We show that populations of neurons of the AOS can be molecularly subdivided based on their current or prior expression of the transcription factorsFoxp2orDbx1. We show that the majority of AOB neurons that project directly to the MeA are of theFoxp2-lineage. Using single cell patch clamp electrophysiology, we further reveal that in addition to sex-specific differences across lineage, the relative contributions of excitatory and inhibitory inputs to MeAFoxp2-lineage neurons differ between sexes. Together, this work uncovers a novel molecular diversity of AOS neurons and lineage- and sex-differences in patterns of connectivity.
SIRT6 is a key regulator of mitochondrial function in the brain
Authors: Smirnov Dmitrii , Eremenko Ekaterina , Stein Daniel , Kaluski Shai , Jasinska Weronika , Consentino Claudia , Martinez-Pastor Barbara , Brotman Yariv , Mostoslavsky Raul , Khrameeva Ekaterina , Toiber Debra
Published: November 2022

SIRT6 is implicated in DNA repair, telomere maintenance, glucose and lipid metabolism and, importantly, it has critical roles in the brain ranging from its development to neurodegeneration. In this work, we combined transcriptomics and metabolomics approaches to characterize the functions of SIRT6 in mice brains. Our analysis revealed that SIRT6 is a critical regulator of mitochondrial activity in the brain. In its absence, there is a mitochondrial deficiency with a global downregulation of mitochondria-related genes and pronounced changes in metabolites content. We predict that SIRT6 can affect mitochondrial functions through its interaction with the transcription factor YY1 that, together, regulate mitochondrial gene expression. Moreover, SIRT6 target genes include SIRT3 and SIRT4, which are significantly downregulated in SIRT6-deficient brains. Our results demonstrate that the lack of SIRT6 leads to decreased mitochondrial gene expression and metabolomic changes of TCA cycle byproducts, including increased ROS production, reduced mitochondrial number, and impaired membrane potential that can be partially rescued by restoring SIRT3 and 4 levels. Importantly, the changes observed in SIRT6 deficient brains are observed in brains of aging people, but the overlapping is greater in patients with Alzheimer’s, Parkinson’s, Huntington’s, and Amyotrophic lateral sclerosis disease. Overall, our results suggest that reduced levels of SIRT6 in the aging brain and neurodegeneration could initiate mitochondrial dysfunction by altering gene expression, ROS production and mitochondrial decay.
Systems-level transcriptional regulation ofCaenorhabditis elegansmetabolism
Authors: Nanda Shivani , Jacques Marc-Antoine , Wang Wen , Myers Chad L , Yilmaz L. Safak , Walhout Albertha JM
Published: November 2022

Metabolism is precisely controlled to ensure organismal development and homeostasis. Several mechanisms regulate metabolism, including allosteric control and transcriptional regulation of metabolic enzymes and transporters. So far, metabolism regulation has mostly been described for individual genes and pathways, and the extent of transcriptional regulation of the entire metabolic network remains largely unknown. Here, we find that more than three-quarters of all metabolic genes are transcriptionally regulated in the nematodeCaenorhabditis elegans. We find that many annotated metabolic pathways are coexpressed, and we use gene expression data and the iCEL1314 metabolic network model to define coregulated sub-pathways in an unbiased manner. Using a large gene expression compendium, we determine the conditions where sub-pathways exhibit strong coexpression. Finally, we develop ‘WormClust’, a web application that enables a gene-by-gene query of genes to view their association with metabolic (sub)-pathways. Overall, this study sheds light on the ubiquity of transcriptional regulation of metabolism and provides a blueprint for similar studies in other organisms, including humans.