bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of Small Cell Lung Cancer Molecular Subtyping Markers to Small Cell Neuroendocrine Carcinoma of the Cervix
Authors: Kim Gilhyang , Kim Milim , Nam Eun Ji , Lee Jung-Yun , Park Eunhyang
Published: November 2023

Cervical small cell neuroendocrine carcinoma (CSCNEC) is a rare, aggressive type of cervical cancer. The treatment for CSCNEC follows the chemotherapeutic regimens used for small cell lung cancer (SCLC), with which it shares similar clinical and histologic features. For the first time, we applied neuroendocrine (NE) and SCLC molecular subtyping immunohistochemical markers [achaete-scute homolog 1 (ASCL1), neurogenic differentiation factor 1 (NEUROD1), POU class 2 homeobox 3 (POU2F3), and yes-associated protein 1] in 45 patients with CSCNEC. For the combined NE score, 51.1% of NE-high and 48.9% of NE-low subtypes were identified. The NE-high subtype tended to show worse progression-free survival and overall survival (OS) than the NE-low subtype (P=0.059 and P=0.07, respectively). Applying the SCLC molecular subtyping, 53.3% of cases were identified as NEUROD1-dominant, 17.8% as ASCL1-dominant, 13.3% as YAP-dominant, and 4.4% as POU2F3-dominant, while 11.1% of cases showed negative expression for all markers; the distribution was different from that of SCLC. The NEUROD1-dominant subtype exhibited the worst OS, while the POU2F3 subtype exhibited the best OS (P=0.003), similar to SCLC. In addition, the ASCL1-dominant and NEUROD1-dominant subtypes showed high NE scores, while yes-associated protein 1-dominant and POU2F3-dominant subtypes showed low NE scores (P=0.008). In multivariate analysis, the NEUROD1 expression was further identified as the independent prognostic factor for worse OS, together with the high FIGO stage. CSCNEC was revealed to be a heterogeneous disease with different biological phenotypes and to share some similarities and differences with SCLC. Regarding the ongoing development of tailored treatments based on biomarkers in SCLC, the application of biomarker-driven individualized therapy would improve clinical outcomes in patients with CSCNEC.
Death by Neurologic Criteria in Children Undergoing Extracorporeal Cardiopulmonary Resuscitation: Retrospective Extracorporeal Life Support Organization Registry Study, 2017–2021
Authors: Joye Raphael , Cousin Vladimir L. , Wacker Julie , Hoskote Aparna , Gebistorf Fabienne , Tonna Joseph E. , Rycus Peter T. , Thiagarajan Ravi R. , Polito Angelo
Published: November 2023

OBJECTIVES:

To determine factors associated with brain death in children treated with extracorporeal cardiopulmonary resuscitation (E-cardiopulmonary resuscitation).

DESIGN:

Retrospective database study.

SETTINGS:

Data reported to the Extracorporeal Life Support Organization (ELSO), 2017–2021.

PATIENTS:

Children supported with venoarterial extracorporeal membrane oxygenation (ECMO) for E-cardiopulmonary resuscitation.

INTERVENTION:

None.

MEASUREMENTS AND MAIN RESULTS:

Data from the ELSO Registry included patient characteristics, blood gas values, support therapies, and complications. The primary outcome was brain death (i.e., death by neurologic criteria [DNC]). There were 2,209 children (≥ 29 d to < 18 yr of age) included. The reason for ECMO discontinuation was DNC in 138 patients (6%), and other criteria for death occurred in 886 patients (40%). Recovery occurred in 1,109 patients (50%), and the remaining 76 patients (4%) underwent transplantation. Fine and Gray proportional subdistribution hazards’ regression analyses were used to examine the association between variables of interest and DNC. Age greater than 1 year (p< 0.001), arterial blood carbon dioxide tension (Paco2) greater than 82 mm Hg (p= 0.022), baseline lactate greater than 15 mmol/L (p= 0.034), and lactate 24 hours after cannulation greater than 3.8 mmol/L (p< 0.001) were independently associated with greater hazard of subsequent DNC. In contrast, the presence of cardiac disease was associated with a lower hazard of subsequent DNC (subdistribution hazard ratio 0.57 [95% CI, 0.39–0.83]p= 0.004).

CONCLUSIONS:

In children undergoing E-cardiopulmonary resuscitation, older age, pre-event hypercarbia, higher before and during ECMO lactate levels are associated with DNC. Given the association of DNC with hypercarbia following cardiac arrest, the role of Paco2management in E-cardiopulmonary resuscitation warrants further studies.
The Impact of Mindfulness-Based Interventions on Objective Physiological Measures of Autonomic Function for Individuals With Medical Conditions: A Review of the Evidence
Authors: Churchill Rachel , Swartz Brenda , Johnston-Dumerauf Anneka , Halaris Angelos
Published: November 2023

Objective

Autonomic dysregulation is common in many medical conditions and can have a widespread, negative impact on multiple bodily systems, leading to poorer health outcomes. Thus, addressing autonomic dysregulation as part of a comprehensive treatment plan is important. The goal of this study was to gain a better understanding of the physiological benefits of a mindfulness-based intervention (MBI) for a population with medical conditions, using validated, objective measures of autonomic functioning.

Methods

We conducted a review of the literature and followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocols. Studies were included if a) participants were diagnosed with a medical condition, b) an MBI was used, and c) objective pre/post measurements of autonomic nervous system function were collected. Medical conditions were included as a category for this review when a minimum of three articles met the criteria for inclusion.

Results

Ten articles met the criteria and included oncology, cardiac, and chronic pain conditions. Clinical recommendations were made based on the Clinical Practice Guideline Process Manual, 2017 Edition by the American Academy of Neurology.

Conclusions

Based on level of evidence, only oncology met the criteria for “possibly effective.” However, there was some evidence of the benefit of MBIs for all three medical conditions, based on individual study findings.
Financial Hardship and Age-Related Decrements in Kidney Function Among Black and White Adults in the Midlife in the United States Study
Authors: Surachman Agus , Harhay Meera , Santos Alexis R. , Daw Jonathan , Alexander Lacy M. , Almeida David M. , Coe Christopher L.
Published: November 2023

Objective

This analysis examined if financial hardship was associated with age-related decrements in kidney function using a material-psychosocial-behavioral framework. We also tested if this association was mediated by comorbidity of cardiometabolic risk factors (obesity, elevated blood pressure, and insulin resistance).

Methods

Data from 1361 non-Hispanic Black and White adults (ages 26–94 years; non-Hispanic Black = 258) were obtained from the Wave 3 and Refresher phases of the Midlife in the United States project. Kidney function was based on serum creatinine–based estimated glomerular filtration rate (eGFR; Chronic Kidney Disease Epidemiology Collaboration formula without race adjustment). Financial hardship was evaluated in three domains: material (income to poverty line ratio, health insurance coverage, and public/government financial assistance), psychological (perceived financial status, control over financial status, and perceived financial strains), and behavioral responses (financial adjustment/coping such as sold possessions and cutting back on spending).

Results

More severe financial hardship (overall score and in each domain) was associated with age-related decrements in eGFR, even after adjusting for sociodemographic, education, and health-related covariates. The association between financial hardship and age-related decrements in eGFR was conditional on sex but not race. Finally, cardiometabolic risk factors mediated the association between financial hardship and age-related decrements in eGFR.

Conclusions

These findings affirm the negative effects of financial hardship on age-related decrements in renal clearance. In addition to incorporating traditionally used indicators of SES, such as education and income, future research on social hallmarks of aging should also consider the role of financial hardship on the aging process and age-related diseases.
Association Between Global Sleep Quality and Coronary Microvascular Function in Male Physicians With Occupational Burnout
Authors: von Känel Roland , Princip Mary , Holzgang Sarah A. , Rossi Alexia , Giannopoulos Andreas A. , Buechel Ronny R. , Zuccarella-Hackl Claudia , Pazhenkottil Aju P.
Published: November 2023

Objective

Occupational burnout has been associated with an increased risk of coronary heart disease, although the mechanisms involved are elusive. We investigated whether poor global sleep quality is associated with impaired coronary microvascular function in male physicians, a professional group at increased risk of burnout.

Methods

Study participants were 30 male physicians with clinical burnout and 30 controls without burnout defined by the Maslach Burnout Inventory. Global sleep quality was measured with the Pittsburgh Sleep Quality Index (PSQI). Endothelium-dependent (cold pressor test) and endothelium-independent (adenosine challenge) coronary microvascular functions were quantified with myocardial perfusion positron emission tomography. In multivariable analyses, the interaction between burnout and the PSQI global score was regressed on measures of coronary microvascular function, adjusting for age, body mass index, physical activity, alcohol consumption, and main effects of burnout and PSQI score.

Results

The prevalence of poor sleepers (PSQI score >5) was 40% in the burnout group and 10% in the control group. Adjusting for covariates, burnout-by-global PSQI score interactions were observed for myocardial blood flow (MBF) at rest (r partial = −0.30, p = .025), endothelium-dependent coronary flow reserve (r partial = −0.26, p = .062), MBF response (r partial = −0.30, p = .028), and hyperemic MBF (r partial = −0.34, p = .012). The global PSQI score was inversely associated with these MBF measures in the burnout group relative to the control group. No significant interactions emerged for endothelium-independent MBF.

Conclusions

In male physicians with occupational burnout, poor global sleep quality was associated with reduced endothelium-dependent coronary microvascular function, suggesting a mechanism by which burnout may affect cardiovascular health.
Proboscis Lateralis With Choanal Atresia
Authors: Gómez Prada Diana Carolina , Restrepo Salamanca Nicolas , Sosa Castro Omar M.
Published: November 2023

The case of a female patient who was born with proboscis lateralis, choanal atresia, and telecanthus is submitted. A report is made on the initial management of this patient, the clinical follow-up that has been carried out so far, and a review of the literature is conducted, taking into account the limited information found in this specific pathology, in order to contribute to its diagnostic orientation and treatment from a plastic and craniofacial surgery point of view.
Primary Neurorraphy of the Frontotemporal Branch of the Facial Nerve in Pediatric Patients
Authors: Üstün G. Gencay , Açil M. Furkan , Sert Gökhan , Menkü Özdemir F. Damla , Uzun Hakan
Published: November 2023

Injuries to the frontotemporal nerve cause visual field deficits, in addition to mental and emotional problems due to the associated facial paralysis. This study aimed to evaluate children treated with primary neurorrhaphy of the frontotemporal nerve and to identify the factors that affect treatment outcome. This retrospective study included children that underwent primary neurorrhaphy between 2015 and 2021 due to frontotemporal nerve injury. Medical records, including patient sex and age, the time from injury to surgery, injury zone, the postsurgery week that frontalis muscle activity was first observed, and the postsurgery week that full symmetry with the opposite eyebrow was achieved, were reviewed. The relationship between treatment success, and age group, sex, postinjury timing of surgery (≤72 versus >72 h), and injury zone, was analyzed. The study included 17 patients (9 males and 8 females) with a mean age of 8.8 years. In all, 11 (64.7%) patients achieved full symmetry following surgery and 3 (17.6%) patients gained some muscle activity, but not symmetrically. Among the patients, 9 underwent surgery within 24 hours of injury, versus 5 patients 3 to 7 days postinjury and 3 patients >1 week after injury. Age, sex, and timing of surgery were not significantly correlated with treatment success. There were significant differences in outcome according to injury zone. Surgical success can be obtained with timely primary neurorrhaphy in pediatric patients with traumatic frontotemporal nerve injury. The most important factor affecting the outcome of primary neurorrhaphy for frontotemporal nerve injury is the injury zone.

Level of Evidence:

Level III—case-control study.
Ventriculoperitoneal Shunt Alone for Spontaneous Cerebrospinal Fluid Rhinorrhea as a Presenting Symptom of Hemi-hydranencephaly
Authors: Zhu Meng , Chen Wujun , Zheng Yan , Xing Dongming , Zhang Jiahui
Published: November 2023

A 27-year-old female patient presented with chronic spontaneous cerebrospinal fluid (CSF) rhinorrhea. She had deformity and weakness on the left side since childhood. Imaging examinations demonstrated hemi-hydranencephaly with a nearly complete absence of the right cerebral hemisphere, which was replaced with a membranous sac filled with CSF. She was accompanied with a frontal midline tumor containing lipids. After ventriculoperitoneal shunt, the CSF rhinorrhea completely ceased and no direct repair of the CSF fistula was necessary. The ventriculoperitoneal shunt procedure changes the CSF flow dynamics and releases the intracranial pressure, which may be a simple and effective procedure for CSF rhinorrhea in hemi-hydranencephaly.
Current Status of Auricular Reconstruction Strategy Development
Authors: Wei Yi , Li Li , Xie Cong , Wei Yangchen , Huang Chufei , Wang Yiping , Zhou Jianda , Jia Chiyu , Junlin Liao
Published: November 2023

Microtia has severe physical and psychological impacts on patients, and auricular reconstruction offers improved esthetics and function, alleviating psychological issues. Microtia is a congenital disease caused by a multifactorial interaction of environmental and genetic factors, with complex clinical manifestations. Classification assessment aids in determining treatment strategies. Auricular reconstruction is the primary treatment for severe microtia, focusing on the selection of auricular scaffold materials, the construction of auricular morphology, and skin and soft tissue scaffold coverage. Autologous rib cartilage and synthetic materials are both used as scaffold materials for auricular reconstruction, each with advantages and disadvantages. Methods for achieving skin and soft tissue scaffold coverage have been developed to include nonexpansion and expansion techniques. In recent years, the application of digital auxiliary technology such as finite element analysis has helped optimize surgical outcomes and reduce complications. Tissue-engineered cartilage scaffolds and 3-dimensional bioprinting technology have rapidly advanced in the field of ear reconstruction. This article discusses the prevalence and classification of microtia, the selection of auricular scaffolds, the evolution of surgical methods, and the current applications of digital auxiliary technology in ear reconstruction, with the aim of providing clinical physicians with a reference for individualized ear reconstruction surgery. The focus of this work is on the current applications and challenges of tissue engineering and 3-dimensional bioprinting technology in the field of ear reconstruction, as well as future prospects.
Association Between Storage Time of Transfused Red Blood Cells and Infection After Clean-contaminated Surgery
Authors: Xu Xiaohan , Zhang Yuelun , Gan Jia , Ye Xiangyang , Yu Xuerong , Huang Yuguang
Published: November 2023

Objective:

To investigate the association between the storage time of transfused red blood cells (RBCs) and risks of infections after clean-contaminated surgery.

Background:

Storage lesions of RBCs can aggravate transfusion-related immunomodulation. Very few randomized controlled trials have investigated the impacts of storage time on postoperative outcomes in noncardiac patients.

Methods:

We included adult patients who had undergone clean-contaminated surgery from 2014 to 2018 and received allogeneic RBC transfusion. In transfusion episode-level analysis, the exposure was the storage time of each transfusion episode. In patient-level analysis, the exposures were the mean, weighted mean, maximum storage time, and Scalar Age of Blood Index of RBCs transfused into each patient. The primary outcome was infections that developed after transfusions within postoperative day 30.

Results:

The 4046 patients were included who received 11604 transfusion episodes. Of these, 1025 (25.3%) patients developed postoperative infections. An increased storage time of transfused RBCs was not associated with increased odds of postoperative infections in either transfusion episode-level analysis [odds ratio (OR), 1.03 per 5 days, 95% CI, 0.95–1.11] or patient-level analysis (mean: OR, 1.02, 95% CI, 0.95–1.10; weighted mean: OR, 1.02, 95% CI, 0.95–1.10; maximum: OR, 1.06, 95% CI, 0.98–1.14; Scalar Age of Blood Index: OR, 0.99, 95% CI, 0.96–1.03), after adjusting 17 confounders.

Conclusions:

Prolonged storage time of transfused RBCs was not associated with increased risks of infections after clean-contaminated surgery.
A metabolomic and proteomic analysis of pathologic hypercoagulability in traumatic brain injury patients after dura violation
Authors: Coleman Julia R. , D’Alessandro Angelo , LaCroix Ian , Dzieciatkowska Monika , Lutz Patrick , Mitra Sanchayita , Gamboni Fabia , Ruf Wolram , Silliman Christopher C. , Cohen Mitchell J.
Published: November 2023

BACKGROUND

The coagulopathy of traumatic brain injury (TBI) remains poorly understood. Contradictory descriptions highlight the distinction between systemic and local coagulation, with descriptions of systemic hypercoagulability despite intracranial hypocoagulopathy. This perplexing coagulation profile has been hypothesized to be due to tissue factor release. The objective of this study was to assess the coagulation profile of TBI patients undergoing neurosurgical procedures. We hypothesize that dura violation is associated with higher tissue factor and conversion to a hypercoagulable profile and unique metabolomic and proteomic phenotype.

METHODS

This is a prospective, observational cohort study of all adult TBI patients at an urban, Level I trauma center who underwent a neurosurgical procedure from 2019 to 2021. Whole blood samples were collected before and then 1 hour following dura violation. Citrated rapid and tissue plasminogen activator (tPA) thrombelastography (TEG) were performed, in addition to measurement of tissue factory activity, metabolomics, and proteomics.

RESULTS

Overall, 57 patients were included. The majority (61%) were male, the median age was 52 years, 70% presented after blunt trauma, and the median Glasgow Coma Score was 7. Compared with pre-dura violation, post-dura violation blood demonstrated systemic hypercoagulability, with a significant increase in clot strength (maximum amplitude of 74.4 mm vs. 63.5 mm; p < 0.0001) and a significant decrease in fibrinolysis (LY30 on tPAchallenged TEG of 1.4% vs. 2.6%; p = 0.04). There were no statistically significant differences in tissue factor. Metabolomics revealed notable increases in metabolites involved in late glycolysis, cysteine, and one-carbon metabolites, and metabolites involved in endothelial dysfunction/arginine metabolism/responses to hypoxia. Proteomics revealed notable increase in proteins related to platelet activation and fibrinolysis inhibition.

CONCLUSION

A systemic hypercoagulability is observed in TBI patients, characterized by increased clot strength and decreased fibrinolysis and a unique metabolomic and proteomics phenotype independent of tissue factor levels.
Surgical management of traumatic sternal body nonunions: Technical tricks and clinical experience
Authors: LaRoque Michael C. , Brahme Indraneel S. , Cole Peter A.
Published: November 2023

BACKGROUND

Rarely, traumatic sternum fractures may result in nonunion, which can have drastic, negative implications. Literature on traumatic sternal nonunion reconstruction outcomes is limited to case reports. We present the surgical principles and report clinical outcomes for seven patients following surgical reconstruction of a traumatic sternal body nonunion.

METHODS

Consecutive adult patients with a nonunion after a traumatic sternum fracture who underwent reconstruction using locking plate technology and iliac crest bone graft at a Level I trauma center from 2013 to 2021 were identified. Demographic, injury, and surgery data was collected, and postoperative patient-reported outcome (PRO) scores were obtained. Patient-reported outcome scores included the one-question single assessment numeric evaluation (SANE), and the combined 10-question global physical health and global mental health values. Injuries were classified and all fractures were mapped onto a sternum template. Postoperative radiographs were reviewed for union.

RESULTS

Of the study's seven patients, five were female, and the mean age was 58 years. Mechanism of injury included motor vehicle collision (5) and blunt object chest trauma (2). The mean time from initial fracture to nonunion fixation was 9 months. Four of the seven patients achieved in-clinic follow-up at ≥12 months (mean = 14.3 months), while the other three achieved ≥6 months of in-clinic follow-up. Six patients completed outcomes surveys ≥12 months after surgery (mean = 28.9 months). Mean PRO scores at final follow-up included: SANE of 75 (out of 100), and global physical health and global mental health of 44 and 47, respectively (US population mean = 50).Six of seven patients achieved known radiographic union.

CONCLUSION

We describe an effective and practical method of achieving stable fixation in traumatic sternal body nonunions as evidenced by the positive clinical outcomes of a seven-patient series. Despite the variation in presentation and fracture morphology of this rare injury, the surgical technique and principles outlined can serve as a useful tool for chest wall surgeons.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level IV.
Flushing and locking management related to central venous catheter occlusion rate among adult patients in acute care: a best practice implementation project
Authors: Fan Chia-Hao , Chu Chung-Ning , Chiu Feng-Han , Chen Chia-Te , Tung Heng-Hsin
Published: November 2023

Introduction and objectives:

A central venous catheter (CVC)—a type of central venous access device (CVAD)—is the most common intervention for critical illnesses. Obstruction of the CVC can lead to fatal consequences. Thus, it is critical to maintain catheter lumen patency. The CVC occlusion rate in a hospital in Taiwan was 33%. This project aimed to decrease the CVC occlusion rate in acute care.

Methods:

This project was conceptually informed by the JBI Evidence-Based Model of Healthcare, in particular, the conceptualization of evidence implementation as inclusive of context analysis, implementation, and evaluation of outcomes using evidence-based quality indicators. As part of the seven-phase implementation process, we used audit and feedback in a pre- and post-test design to measure baseline compliance. Based on the initial audit, we developed an implementation strategy responsive to the identified gaps in compliance. We then undertook a final audit to measure changes in compliance to evaluate our implementation effects. The JBI software, PACES, and the situational analysis software, GRiP, were used for data collection and implementation planning. There were six evidence-based criteria, with a sample size of 30 nurses for each criterion. The team carried out the project from September 2022 to January 2023.

Results:

Post-implementation audit compliance rates increased to 100% for the following criteria: the organization had a standardized flushing and locking solution protocol (0%), the CVAD lumen was locked upon completion of the final flush (10%), a single-dose system was used for flushing and locking the CVAD (60%), and preservative-free 0.9% sodium chloride was used to flush the CVAD (60%). Furthermore, the CVC occlusion rate decreased from 33% to 5%.

Conclusions:

The project successfully decreased the rate of CVC occlusion and increased the competence of nurses in acute care settings. The implementation of best practices in clinical care should focus on leadership, cross-department coordination, education, and innovation.
Spanish versions and validation of a series of rating scales and visual analogue scales to assess the subjective effects of cannabis
Authors: Sainz-Cort Alberto , Martín-Islas Marta , Oña Genís , Jimenez-Garrido Daniel , López-Navarro Miriam , Muñoz-Marron Elena , Viejo-Sobera Raquel , Bouso Jose Carlos
Published: November 2023

Cannabis is being legalized for medical and recreational purposes all around the world. However, the understanding of the psychological effects of cannabis is still limited, and it has been previously linked to mental disorders such as schizophrenia. Lately, new scales have been created and adapted to measure its psychological effects. The aim of this study is to create Spanish versions of some of these scales and test their psychometric characteristics. One hundred sixteen participants were recruited from Cannabis Social Clubs (CSC) in Barcelona, Spain. Participants under the effects of their own cannabis completed the Cannabis Experience Questionnaire–modified version (CEQ-mv), Addiction Research Centre Inventory-18 (ARCI-18), Psychotomimetic States Inventory (PSI) and Visual Analogue Scales (VAS). Questionnaires were completed in the CSC, providing a naturalistic setting for the study. Exploratory factor analysis and internal consistency were analyzed. PSI was reduced from a 6-factor to a 4-factor model with adequate to low reliability, ARCI-18 was reduced from a 3-factor to a 2-factor model with good reliability, and VAS were reduced from a 4-factor to a 3-factor model, also with good reliability. These questionnaires showed adequate reliability and can be used in future studies to test the subjective effects of cannabis in clinical and naturalistic settings.
High-cycle fatigue life prediction of L-PBF AlSi10Mg alloys: a domain knowledge-guided symbolic regression approach
Authors: Yu Huan , Hu Yanan , Kang Guozheng , Peng Xin , Chen Bingqing , Wu Shengchuan
Published: November 2023

The large scatter in high-cycle fatigue (HCF) life poses significant challenges to safe and reliable in-service assessment of additively manufactured metal components. Previous investigations have indicated that inherent manufacturing defects are a critical factor affecting the fatigue performance of the components, and the HCF life is significantly influenced by the geometric parameters of the critical defects inducing crack nucleation. Therefore, it is highly important to elucidate the correlation of the HCF life with the geometric parameters of critical defects. This study proposes a new fatigue life prediction model for laser additively manufactured AlSi10Mg alloys by including the combined effects of loading stress and defect geometries (size, location and morphology) in terms of domain knowledge-guided symbolic regression (SR). Domain knowledge is extracted from the semi-empirical Murakami,
Z
-parameter and
X
-parameter fatigue life models to establish the variable subtrees. The results show that compared with these semi-empirical models, the domain knowledge integration-based SR model has higher prediction accuracy and generalization ability. Moreover, compared with traditional ‘black box’ machine learning models, SR excels at balancing prediction accuracy and model interpretability, which provides useful insights into the relationship between fatigue life and defect geometries.

This article is part of the theme issue 'Physics-informed machine learning and its structural integrity applications (Part 2)'.
Magnetic flux leakage defect size estimation method based on physics-informed neural network
Authors: Xiong Yi , Liu Shuai , Hou Litao , Zhou Taotao
Published: November 2023

Magnetic flux leakage (MFL) is a magnetic method of non-destructive testing for in-pipe defect detection and sizing. Despite the fact that recent developments in machine learning have revolutionized disciplines like MFL defect size estimation, the most current methods for quantifying pipeline defects are primarily data-driven, which may violate the underlying physical knowledge. This paper proposes a physics-informed neural network-based method for MFL defect size estimation. The training process of neural network is guided by the MFL data and the physical constraints that is mathematically represented by the magnetic dipole model. We use synthetic MFL data produced by a virtual MFL testing of pipeline defects to validate the proposed method through a comparison to purely data-driven neural networks and support vector machines. The findings imply that the physics-informed strategy can both improve predictive accuracy and mitigate physical violations in MFL testing, providing us with a better knowledge of how neural networks perform in defect size estimation.

This article is part of the theme issue ‘Physics-informed machine learning and its structural integrity applications (Part 2)’.
Methanolobus mangrovi sp. nov. and Methanolobus sediminis sp. nov, two novel methylotrophic methanogens isolated from mangrove sediments in China
Authors: Zhou Jinjie , Zhang Hanyun , Zhang Cui-Jing , Li Meng
Published: November 2023

Two methylotrophic methanogens, designated strains FTZ2T and FTZ6T, were isolated from mangrove sediment sampled in Futian Mangrove Nature Reserve in Shenzhen, PR China. Cells of strains FTZ2T and FTZ6T were cocci, with diameters of 0.6–1.0 µm and 0.6–0.9 µm, respectively. Both strains grew on methanol, methylamine, dimethylamine and trimethylamine, but not on acetate, formate, H2/CO2, choline, betaine or dimethyl sulphide. Strain FTZ2T grew at 10–37 °C (optimally at 33 °C), pH 5.5–8.0 (optimally at pH 7.0) and 0–1.03 M NaCl (optimally at 0.17 M NaCl). In contrast, strain FTZ6T grew at 15–42 °C (optimally at 37 °C), pH 5.0–7.5 (optimally pH 6.5) and 0–1.03 M NaCl (optimally at 0.17 M NaCl). Both strains required magnesium for growth and were susceptible to sodium dodecyl sulphate. Biotin was required for the growth of strain FTZ2T but not of strain FTZ6T. The genomic G+C contents of strains FTZ2T and FTZ6T were 41.6 and 40.9 mol%, respectively. Phylogenetic analyses revealed that strain FTZ2T was mostly related to

Methanolobus psychrotolerans

YSF-03T, with 16S rRNA gene similarity of 98.6 %, an average nucleotide identity (ANI) of 82.5 %, and a digital DNA–DNA hybridization (dDDH) of 24.6 %. While strain FTZ6T was mostly related to

Methanolobus vulcani

PL-12/MT, with 16S rRNA gene similarity of 99.4 %, an ANI of 88.6% and a dDDH of 34.6 %. Based on phenotypic, phylogenetic and genotypic evidence, two novel species of the genus

Methanolobus

, Methanolobus mangrovi sp. nov. and Methanolobus sediminis sp. nov., are proposed. The type strain of M. mangrovi sp. nov. is FTZ2T (=CCAM 1276T=JCM 39396T) and the type strain of M. sediminis sp. nov. is FTZ6T (=CCAM 1277T=JCM 39397T).
Brd2 is dispensable for genome compartmentalization and replication timing
Authors: Hinojosa-Gonzalez Laura , Turner Jesse L. , Sasaki Takayo , Ay Ferhat , Gilbert David M.
Published: November 2023

Replication Timing (RT) refers to the temporal order in which the genome is replicated during S phase. Early replicating regions correlate with the transcriptionally active, accessible euchromatin (A) compartment, while late replicating regions correlate with the heterochromatin (B) compartment and repressive histone marks. Previously, widespread A/B genome compartmentalization changes were reported following Brd2 depletion. Since RT and A/B compartmentalization are two of the most highly correlated chromosome properties, we evaluated the effects of Brd2 depletion on RT. We performed E/L Repli-Seq following Brd2 depletion in the previously described Brd2 conditional degron cell line and found no significant alterations in RT after Brd2 KD. This finding prompted us to re-analyze the Micro-C data from the previous publication. We report that we were unable to detect any compartmentalization changes in Brd2 depleted cells compared to DMSO control using the same data. Taken together, our findings demonstrate that Brd2 depletion alone does not affect A/B compartmentalization or RT in mouse embryonic stem cells.
Structures of theStaphylococcus aureusribosome inhibited by fusidic acid and fusidic acid cyclopentane
Authors: González-López Adrián , Larsson Daniel S. D. , Koripella Ravi Kiran , Cain Brett N. , Chavez Martin Garcia , Hergenrother Paul J. , Sanyal Suparna , Selmer Maria
Published: November 2023

The antibiotic fusidic acid (FA) is used to treatStaphylococcus aureusinfections. It inhibits protein synthesis by binding to elongation factor G (EF-G) and preventing its release from the ribosome after translocation. While FA is only effective against gram-positive bacteria, the available structures of FA-inhibited complexes are from gram-negative model organisms. To fill this knowledge gap, we solved cryo-EM structures of theS. aureusribosome in complex with mRNA, tRNA, EF-G and FA to 2.5 Å resolution and the corresponding complex structures with the recently developed FA derivative FA-cyclopentane (FA-CP) to 2.0 Å resolution. With both FA variants, the majority of the ribosomal particles are observed in chimeric hybrid state and only a minor population in post-translocational state. As expected, FA binds in a pocket between domains I, II and III of EF-G and the sarcin-ricin loop of 23S rRNA. FA-CP binds in an identical position, but its cyclopentane moiety provides additional contacts to EF-G and 23S rRNA, suggesting that its improved resistance profile towards mutations in EF-G is due to higher-affinity binding. These high-resolution structures reveal new details about theS. aureusribosome, including confirmation of many rRNA modifications, and provide an optimal starting point for future structure-based drug discovery on an important clinical drug target.
Unveiling unique microbial nitrogen cycling and novel nitrification drivers in coastal Antarctica
Authors: Han Ping , Tang Xiufeng , Koch Hanna , Dong Xiyang , Hou Lijun , Wang Danhe , Zhao Qian , Li Zhe , Liu Min , Lücker Sebastian , Shi Guitao
Published: November 2023

Although microbial nitrogen (N) cycling plays a pivotal role in Antarctic ecosystems, its underlying mechanisms are largely uncharted. In this study, we unravel the biological origin of nitrate via triple oxygen isotopic composition analysis and systematically profile functional N-cycling genes within soil and lake sediment samples from the ice-free areas of East Antarctica. We successfully reconstruct 1,968 metagenome-assembled genomes (MAGs) spanning 29 microbial phyla, enabling the analysis of the presence or absence of 52 diverse metabolic marker genes. Consistent with quantitative data, our metagenomic analyses confirm the active processes of microbial nitrogen fixation, nitrification, and denitrification. We find no detectable anaerobic ammonium oxidation (anammox) processes, underscoring a unique microbial N-cycling dynamic in the region. Notably, we identify the predominance of complete ammonia-oxidizing (comammox)Nitrospira, a recently discovered bacterial guild capable of performing the entire nitrification process within a single organism. Further genomic investigations reveal their adaptive strategies in the Antarctic environment. These strategies likely involve the synthesis of trehalose to counteract cold stress, high substrate affinity to efficiently utilize available resources, and alternative metabolic pathways to adapt to nutrient-scarce conditions. Their significant role in the nitrification process is validated through13C-DNA-based stable isotope probing (DNA-SIP). This research provides a comprehensive illustration of nitrification’s crucial contribution to the nitrogen budget in coastal Antarctica, highlighting comammoxNitrospiraclade B as a novel nitrifying agent and shedding new light on the complex biogeochemical processes of nitrogen cycling in coastal Antarctica.
Preserved particulate organic carbon is likely derived from the subsurface sulfidic photic zone of the Proterozoic Ocean: evidence from a modern, oxygen-deficient lake
Authors: Cohen Ashley Brooke , Taylor Gordon T , Henkes Gregory , Weber Felix , Christensen Lisa N , Yagudaeva Milana , Lo Evan , McCormick Michael
Published: November 2023

I-Abstract

Biological processes in the Proterozoic Ocean are often inferred from modern oxygen-deficient environments (MODEs) or from stable isotopes in preserved sediment. To-date, few MODE studies have simultaneously quantified carbon fixation genes and attendant stable isotopic signatures. Consequently, how carbon isotope patterns reflect these pathways has not been thoroughly vetted. Addressing this, we profiled planktonic productivity and quantified carbon fixation pathway genes and associated carbon isotope values of size-fractionated (0.2 – 2.7 and > 2.7 μm) particulate organic carbon values (813CPOC) from meromictic Fayetteville Green Lake, NY, USA. The high-O2Calvin-Benson-Bassham (CBB) gene (cbbL)was most abundant in the <2.7 μm size fraction in shallow oxic and deep hypoxic waters, corresponding with cyanobacterial populations. The low-O2CBB gene (cbbM)was most abundant near the lower oxycline boundary in the larger size fraction, coincident with purple sulfur bacteria populations. The reverse citric acid cycle gene (aclB)was equally abundant in both size fractions in the deepest photic zone, coinciding with green sulfur bacteria populations. Methane coenzyme reductase A (mcrA), of anaerobic methane cyclers, was most abundant at the lower oxycline boundary in both size fractions, coinciding withMethanoregulapopulations. 813CPOCvalues overlapped with the high-O2CBB fixation range except for two negative excursions near the lower oxycline boundary, likely reflecting assimilation of isotopically-depleted groundwater-derived inorganic carbon by autotrophs and acetate oxidation by sulfate-reducers. Throughout aphotic waters, 813CPOCvalues of the large size fraction became 13C-enriched, likely reflecting abundant purple sulfur bacterial aggregates. Microalgal-like isotopic signatures corresponded with increases incbbL,cbbMandaclB, and enrichment of exopolymer-rich prokaryotic photoautotrophs aggregates. Results suggest that 813CPOCvalues of preserved sediments from areas of the Proterozoic Ocean with sulfidic photic zones may reflect a mixture of alternate carbon-fixing populations exported from the deep photic zone, challenging the paradigm that sedimentary stable carbon isotope values predominantly reflect oxygenic photosynthesis from surface waters.
A thermodynamic framework for nonequilibrium self-assembly and force morphology tradeoffs in branched actin networks
Authors: Rennert Elisabeth , Vaikuntanathan Suriyanarayanan
Published: November 2023

Branched actin networks are involved in a variety of cellular processes, most notably the formation of lamellipodia in the leading edge of the cell. These systems adapt to varying loads through force dependent assembly rates that allow the network density and material properties to be modulated. Recent experimental work has described growth and force feedback mechanisms in these systems. Here, we consider the role played by energy dissipation in determining the kind of growth-force-morphology curves obtained in experiments. We construct a minimal model of the branched actin network self assembly process incorporating some of the established mechanisms. Our minimal analytically tractable model is able to reproduce experimental trends in density and growth rate. Further, we show how these trends depend crucially on entropy dissipation and change quantitatively if the entropy dissipation is parametrically set to values corresponding to a quasistatic state. Finally, we also identify the potential energy costs of adaptive behavior by branched actin networks, using insights from our minimal models. We suggest that the dissipative cost in the system beyond what is necessary to move the load may be necessary to maintain an adaptive steady state. Our results hence show how constraints from stochastic thermodynamics and non-equilibrium thermodynamics may bound or constrain the structures that result in such force generating processes.
Protein Stability Prediction by Fine-tuning a Protein Language Model on a Mega-scale Dataset
Authors: Chu Simon K. S. , Siegel Justin B.
Published: November 2023

The stability of a protein is crucial to its utility in industrial applications. While engineering campaigns can now be routinely used to enhance protein thermal stability to the level needed in an industrial setting, there is a significant desire to fast-track these efforts through predictive tools allowing one to jump in a minimal number of design iterations to a highly stabilized protein. In this work, we explore utilizing a mega-scale dataset for development of a protein language model tuned for stability. This model is trained on the folding stability of 528k sequences derived from 461 small protein domains and designs, and can accommodate deletions, insertions, and multiple-point mutations. We show that a protein language model can be fine-tuned to predict folding stability. The fine-tuned protein language model, named ESMtherm, performs reasonably on small protein domains and generalizes to sequences distal from the training set. Lastly, we discuss its limitations when compared to other state-of-the-art methods in generalizing to larger protein scaffolds and highlight the need of large-scale stability measurement on a diverse dataset that represents the distribution of sequence lengths commonly observed in nature.
Feedback inhibition by a descending GABAergic neuron regulates timing of escape behavior inDrosophilalarvae
Authors: Zhu Jiayi , Boivin Jean-Christophe , Garner Alastair , Ning Jing , Zhao Yi Qing , Ohyama Tomoko
Published: November 2023

Escape behaviors help animals avoid harm from predators and other threats in the environment. Successful escape relies on integrating information from multiple stimulus modalities (of external or internal origin) to compute trajectories toward safe locations, choose between actions that satisfy competing motivations, and execute other strategies that ensure survival. To this end, escape behaviors must be adaptive. When aDrosophila melanogasterlarva encounters a noxious stimulus, such as the focal pressure a parasitic wasp applies to the larval cuticle via its ovipositor, it initiates a characteristic escape response. The escape sequence consists of an initial abrupt bending, a corkscrew-like rolling, and finally rapid crawling. Previous work has shown that the detection of noxious stimuli primarily relies on class IV multi dendritic arborization neurons (Class IV neurons) located beneath the body wall, and more recent studies have identified several important components in the nociceptive neural circuitry involved in rolling. However, the neural mechanisms that underlie the rolling-escape sequence remain unclear. Here we present both functional and anatomical evidence suggesting that bilateral descending neurons within the subesophageal zone ofD. melanogasterlarva play a crucial role in regulating the termination of rolling and subsequent transition to escape crawling. We demonstrate that these descending neurons (designated SeIN128) are inhibitory and receive inputs from a second-order interneuron upstream (Basin-2) and an ascending neuron downstream of Basin-2 (A00c). Together with optogenetic experiments showing that co-activation of SeIN128 neurons and Basin-2 influence the temporal dynamics of rolling, our findings collectively suggest that the ensemble of SeIN128, Basin-2, and A00c neurons forms a GABAergic feedback loop onto Basin-2, which inhibits rolling and thereby facilitates the shift to escape crawling.
Genomic and phenotypic stability of fusion-driven pediatric Ewing sarcoma cell lines
Authors: Kasan Merve , Siebenlist Jana , Sill Martin , Öllinger Rupert , de Álava Enrique , Surdez Didier , Dirksen Uta , Oehme Ina , Scotlandi Katia , Delattre Olivier , Müller-Nurasyid Martina , Rad Roland , Strauch Konstantin , Grünewald Thomas G. P. , Cidre-Aranaz Florencia
Published: November 2023

Human cancer cell lines are the mainstay of cancer research. Recent reports showed that highly mutated adult carcinoma cell lines (mainly HeLa and MCF-7) present striking diversity across laboratories and that long-term continuous culturing results in genomic/transcriptomic heterogeneity with strong phenotypical implications. This highlighted how despite human cell line models being powerful tools for cancer research, the findings derived from their use may present limitations in terms of reproducibility. However, to what extent these conclusions can be generalized to the majority of cancer cell lines remained unexplored. Here, we hypothesized that oligomutated pediatric sarcoma cell lines driven by a chimeric oncogenic transcription factor (COTF), such as Ewing sarcoma (EwS), were genetically and phenotypically more stable than the previously investigated (adult) carcinoma cell lines. A comprehensive molecular and phenotypic characterization of multiple EwS cell line strains in direct comparison to the HeLa and MCF-7 cell lines, together with a simultaneous analysis during 12 months of continuous cell culture showed that COTF-driven pediatric sarcoma cell line strains are genomically more stable than adult carcinoma strains, display remarkably stable and homogenous transcriptomes, and exhibit uniform and stable drug response. The analysis of multiple EwS cell lines subjected to long-term continuous culture conditions revealed that variable degrees of genomic/transcriptomic/phenotypic may be observed among COTF-driven cell lines, further exemplifying that the potential for reproducibility of in vitro scientific results may be rather understood as a spectrum, even within the same tumor entity.
A naturally occurring variant ofMBD4causes maternal germline hypermutation in primates
Authors: Stendahl Alexandra M. , Sanghvi Rashesh , Peterson Samuel , Ray Karina , Lima Ana C. , Rahbari Raheleh , Conrad Donald F.
Published: November 2023

As part of an ongoing genome sequencing project at the Oregon National Primate Research Center, we identified a rhesus macaque with a rare homozygous frameshift mutation in the gene methyl-CpG binding domain 4, DNA glycosylase (MBD4). MBD4 is responsible for the repair of C > T deamination mutations at CpG dinucleotides and has been linked to somatic hypermutation and cancer predisposition in humans. We show here that MBD4-associated hypermutation also affects the germline: The six offspring of theMBD4-null dam have a fourfold to sixfold increase in de novo mutation burden. This excess burden was predominantly C > T mutations at CpG dinucleotides consistent withMBD4loss of function in the dam. There was also a significant excess of C > T at CpA sites, indicating an important, unappreciated role for MBD4 to repair deamination in CpA contexts. TheMBD4-null dam developed sustained eosinophilia later in life, but we saw no other signs of neoplastic processes associated withMBD4loss of function in humans nor any obvious disease in the hypermutated offspring. This work provides the first evidence for a genetic factor causing hypermutation in the maternal germline of a mammal and adds to the very small list of naturally occurring variants known to modulate germline mutation rates in mammals.